CN120189576A - Multimodal fluid delivery device - Google Patents

Abstract

The present invention relates to a multi-mode fluid delivery device for drugs and vaccines for use in the fields of human clinical medicine and animal health. The invention combines all advantages of a needleless injection mode, a micro needle injection mode and a needleless injection mode through the design of a multi-needle and multi-hole matched detachable injection head and a needle part contained in the multi-needle and multi-hole matched detachable injection head, eliminates the defects of the multi-needle and multi-hole matched detachable injection head, realizes flexible switching among the three modes of needleless, micro needle and needleless, improves single delivery quantity and delivery efficiency of medicines and vaccines while painless and not damaging skin, eliminates weeping, delivers the medicines and the vaccines to one or more target positions with different depths of a human body, optimizes pharmacokinetics by controlling three-dimensional dispersion of the medicines and the vaccines at the target positions, and greatly improves contact effect and bioavailability of the medicines and the vaccines and internal tissues. The invention also provides related components, systems and related pharmaceutical combination products.

Description

Multi-mode fluid delivery device

Technical Field

The invention relates to the field of medical equipment, in particular to a multi-mode drug and vaccine delivery device and a medical instrument combination product used in the fields of human clinical medical treatment and animal health care.

Background

In the current field of drug and vaccine delivery, needle, microneedle and needleless injection are the three main delivery modes. Traditional needle injections are widely used for the delivery of various drugs and vaccines, but drugs and vaccines injected into the body through needle injections are in an aggregated state, which is unfavorable for drug absorption and metabolism, and needle injections are often accompanied by pain and infection risk of patients, thus causing psychological and physical burden to patients, such as needle terrorism, which is a main cause of the inability of vaccination in many countries worldwide. While microneedle injection technology, while capable of reducing pain and trauma, has limited delivery sites and limited efficiency and applicability in delivering macromolecular drugs or high dose vaccines. In contrast, needleless injection techniques greatly increase the dispersion of the drug after delivery into the body and reduce the risk of pain and infection. However, the application and popularization of the needle-free injection technology alone in the clinical and animal health care fields is still challenging, mainly because the needle-free injection needs to break the skin by using high-pressure liquid jet, thus greatly limiting the area of the delivered liquid jet and the delivered drug dose, and in addition, the scientific research of penetration and accurate delivery performance of the needle-free injection is insufficient, especially in terms of jet flow rate, drug chemistry, drug dispersion mode, needle-free injection aperture design, and the influence of different biological media (such as epidermis, subcutaneous, muscle, etc. of human and animal) on the drug delivery performance.

In practical applications, the restriction of the injection aperture and the high requirements for skin fit of needleless injection technology have made their popularity limited. This technique is prone to leakage of the drug solution due to the presence of hair, and it is difficult to precisely control the injection position, depth, and dispersion of the drug solution. Thus, despite the significant advantages of needleless injection technology in theory, there are challenges in practical clinical applications. In addition, the stimulation of drug metabolism and vaccine immunogenicity has placed high standard requirements on three-dimensional dispersion and accurate positioning of drugs and vaccines in vivo, and existing needleless injection techniques still face unresolved difficulties in meeting these requirements, such as increasing the dispersion requires increasing the area of the liquid jet, but the increase in the area of the liquid jet can cause skin disruption difficulties, bleeding and injury to a large extent.

One significant gap in current drug delivery technology is how to effectively combine the advantages of needle technology precise positioning and high dose delivery, the advantages of needleless injection technology high dispersion, and the advantages of microneedle injection technology multi-point delivery to meet the specific needs of different drugs and vaccines. In particular, the prior art has failed to provide a satisfactory answer in seeking a solution that enables flexible switching between different modes of injection depending on the clinical situation.

The description of the background art is only for the purpose of facilitating an understanding of the relevant art and is not to be taken as an admission of prior art.

Disclosure of Invention

The invention aims to provide a multi-mode fluid delivery device, which combines the advantages of needleless delivery, needleless delivery and microneedle delivery to solve the problems of the three delivery modes, thereby improving the stability, the accuracy and the bioavailability of a delivery system.

Embodiments of the present invention provide a multi-mode fluid delivery device comprising:

a tube for containing a fluid, the tube having a first end and a second end, the second end having a self-closing resilient portion disposed therein or an aperture for distributing the fluid within the tube;

An injection head detachably connected to the tube, the injection head comprising one or more needle members configured to removably interface with a self-closing spring in the second end or a hole for fluid within a dispensing tube, and

A power mechanism including a piston disposed in the first end of the tube capable of pushing the fluid or operatively connected to the piston to apply delivery pressure to the piston pushing the fluid.

Additional optional features and technical effects of embodiments of the invention are described in part below and in part will be apparent from reading the disclosure herein.

Drawings

Embodiments of the present invention will hereinafter be described in conjunction with the appended drawings, wherein like or similar reference numerals denote like or similar elements, and wherein:

FIG. 1 shows a schematic block diagram of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 2 shows a schematic block diagram of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 3 shows a schematic needle arrangement of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 4 shows a schematic needle arrangement of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 5 shows a schematic needle arrangement of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 6 shows a schematic needle arrangement of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 7 shows a schematic needle piece schematic view of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 8 shows a schematic needle piece schematic view of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 9 shows a schematic view of a multi-mode fluid delivery device with a needle member in-line arrangement according to an embodiment of the present invention;

FIG. 10 shows a schematic view of a multi-mode fluid delivery device with a needle member in-line arrangement according to an embodiment of the present invention;

FIG. 11 shows a schematic view of a multi-mode fluid delivery device with a needle member in-line arrangement according to an embodiment of the present invention;

FIG. 12 shows a schematic view of a multi-mode fluid delivery device according to the present invention in a straight line arrangement of needle members;

FIG. 13 shows a schematic diagram of an array arrangement of needle members of a multi-mode fluid delivery device in accordance with an embodiment of the present invention;

FIG. 14A shows a schematic needle arrangement diagram of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 14B shows a schematic needle arrangement diagram of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 15 shows a schematic view of a needle arrangement of different pinhole apertures of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 16 shows a schematic view of a needle arrangement of different pinhole apertures of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 17 shows a schematic view of a needle arrangement of different pinhole apertures of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 18 shows a schematic view of a needle arrangement of different pinhole apertures of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 19 shows a schematic view of an annular arrangement of needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 20 shows a schematic view of an annular arrangement of needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 21 shows a schematic view of a multi-set coaxial annular arrangement of needle components of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 22 illustrates a schematic view of a multi-set needle assembly coaxial annular arrangement of a multi-mode fluid delivery device in accordance with an embodiment of the present invention;

FIG. 23 shows a multi-set needle assembly coaxial annular schematic of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 24 shows a schematic view of a needle arrangement of a central needle and a peripheral needle of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 25 shows a schematic view of the needle arrangement of the central and peripheral needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 26 shows a schematic view of the needle arrangement of the central and peripheral needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 27 shows a schematic view of the needle arrangement of the central and peripheral needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 28 shows a schematic view of the needle arrangement of the central and peripheral needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 29 shows a schematic view of the needle arrangement of the central and peripheral needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 30 shows a schematic view of the needle arrangement of the central and peripheral needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 31 shows a schematic view of the needle arrangement of the central and peripheral needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 32 shows a schematic view of the needle arrangement of the central and peripheral needle members of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 33 shows a schematic injector head schematic diagram of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 34 shows a schematic injector head schematic view of a multi-mode fluid delivery device according to an embodiment of the invention;

FIG. 35 shows a schematic needle set diagram of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 36 shows a schematic needle set diagram of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 37 shows a schematic needle set diagram of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 38 shows a schematic view of a needleless needle cannula of a multi-mode fluid delivery device in accordance with an embodiment of the present invention;

FIG. 39 shows a schematic view of a needleless needle cannula of a multi-mode fluid delivery device in accordance with an embodiment of the present invention;

FIG. 40 shows a schematic view of a needle arrangement of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 41 illustrates a second end schematic view of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 42 shows a schematic block diagram of a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 43 shows a schematic simulation model block diagram of multi-mode fluid delivery device delivery in accordance with a specific embodiment of the present invention;

FIG. 44 illustrates a schematic of a porous dispersion effect delivered by a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 45 illustrates a schematic of a porous dispersion effect delivered by a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 46 illustrates a schematic of a porous dispersion effect delivered by a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 47 illustrates a schematic of a porous dispersion effect delivered by a multi-mode fluid delivery device according to an embodiment of the present invention;

FIG. 48 illustrates a schematic view of a needle arrangement delivered by a multi-mode fluid delivery device according to one embodiment of the present invention;

FIG. 49 shows a line graph of immunological test data delivered by a multi-mode fluid delivery device according to one particular embodiment of the present invention;

FIG. 50 shows a line drawing of immunoassay data delivered by a multi-mode fluid delivery device in accordance with an embodiment of the present invention, and

FIG. 51 shows a line graph of immunoassay data delivered by a multi-mode fluid delivery device according to one specific embodiment of the present invention.

Detailed Description

The present invention will be described in further detail with reference to the following detailed description and the accompanying drawings, in order to make the objects, technical solutions and advantages of the present invention more apparent. The exemplary embodiments of the present invention and the descriptions thereof are used herein to explain the present invention, but are not intended to limit the invention.

The term "comprising" and variations thereof as used herein means open ended, i.e., "including but not limited to. The term "or" means "and/or" unless specifically stated otherwise. The term "based on" means "based at least in part on". The terms "one example embodiment" and "one embodiment" mean "at least one example embodiment. The term "another embodiment" means "at least one additional embodiment". The terms "first," "second," and the like, may refer to different or the same object. Other explicit and implicit definitions are also possible below.

In various embodiments of the present invention, as shown in fig. 1 and 2, a multi-mode fluid delivery device, particularly a drug and vaccine multi-mode fluid delivery device, is provided that may include a tube 100 for containing a fluid, the tube 100 having a first end 110 and a second end 120. As shown in fig. 1, the second end 120 may have apertures 121 therein for distributing the fluid within the tube. Additionally or alternatively, as shown in fig. 2, a self-closing resilient portion 122 may be provided in the second end 120.

The multi-mode fluid delivery device may further comprise an injection head 200 detachably connected to the tube 100, the injection head 200 comprising one or more needle members 210. The one or more needle members 210 are configured to removably interface with the self-closing resilient portion 122 in the second end 120 or the aperture 121 for the fluid 130 within the dispensing tube 100.

The multi-mode fluid delivery device may further comprise a power mechanism 300, the power mechanism 300 comprising a piston 310 disposed in the first end 110 of the tube 100 capable of pushing the fluid 130 or operatively connected to the piston 310 to apply a delivery pressure to the piston 310 pushing the fluid 130.

In some embodiments of the present invention, as shown in fig. 2, 3 self-sealing elastic parts 122 are provided in the second end 120, and the 3 needle members 210 are configured to be removably connected with the self-sealing elastic parts 122 in the second end 120, specifically, configured such that the 3 needle members 210 are inserted into the corresponding second ends 120 and 3 self-sealing elastic parts 122 are provided.

In some embodiments of the present invention, the self-sealing elastic portion 122 is formed by filling the hole 121 for distributing the fluid in the tube provided in the second end 120 with silicone, and there is no limitation in the specific composition of the silicone, and likewise, the hole 121 may be filled with a material different from silicone and suitable for being inserted by the plurality of needle members 210, and there is no limitation in this regard.

In some embodiments of the present invention, as shown in fig. 1 and 2, the piston 310 may be provided as a separate component, and the power mechanism 300 is configured and adapted to operatively connect the piston 310 to apply delivery pressure to the piston 310. It is also contemplated that in other embodiments of the present invention, the power mechanism 300 may be integrally formed with the piston 310.

In some embodiments of the present invention, the driving mode of the power mechanism 300 may include any one of compressed gas driving, spring driving, electromagnetic driving, or a combination thereof, for example, in some embodiments, the power mechanism 300 may be driven by compressed gas, such as compressed nitrogen or compressed carbon dioxide, compressed mechanical spring driving, or may be driven by a piezoelectric actuation device, which is not limited herein.

In some embodiments of the present invention, compared to manual needle injection (the pushing speed of the piston inside the needle tube is about 0.01 m/s), the piston speed of the multi-mode fluid delivery device of the present invention when the piston 310 pushes the fluid 130 inside the tube 100 is 10 times or more than the manual needle injection piston speed, and the piston speed when the piston 310 pushes the fluid 130 is 0.05m/s to 0.50m/s, preferably 0.09m/s to 0.25m/s, and more preferably 0.14m/s to 0.20m/s.

In some embodiments of the present invention, the outlet jet velocity of the fluid 130 of the multi-mode fluid delivery device of embodiments of the present invention is greater than or equal to 10m/s, preferably greater than or equal to 50m/s, more preferably greater than or equal to 100m/s, and even more preferably greater than or equal to 150m/s, as opposed to manual needle injection (the outlet jet velocity of the fluid ejected by the needle is about 2 m/s) when the fluid 130 is pushed away from the plurality of apertures 121 in the second end 120 or the one or more needle members 210 of the injection head 200 by the piston 310.

In some embodiments of the invention, at least one of the one or more needle members 210 is inserted substantially into a human or animal body.

In some embodiments of the invention, at least one of the one or more needle members is substantially inserted into a human or animal body;

In some embodiments of the present invention, at least one of the one or more needle members has an aperture in the range of 0.06mm to 1.50mm, more preferably in the range of 0.11mm to 1.00mm, still more preferably in the range of 0.11mm to 0.50 mm;

In some embodiments of the invention, at least one of the self-sealing resilient portion or the aperture for the fluid in the dispensing tube has a diameter in the range of 0.06mm to 1.50mm, more preferably in the range of 0.11mm to 1.00mm, still more preferably in the range of 0.11mm to 0.50 mm.

In some embodiments of the invention, the total fluid delivery area of the plurality of needle members or the plurality of apertures for distributing the fluid within the tube is 0.009mm² or more, preferably 0.020mm² or more, more preferably 0.053mm² or more, more preferably 0.28mm² or more, and the single aperture area of the needle member or aperture is 0.0028 to 0.035mm², preferably 0.0028 to 0.020mm², more preferably 0.0028 to 0.009mm², wherein the single aperture area of the needle member refers to a single aperture area calculated from the needle inner diameter of the needle member.

In embodiments of the present invention, the multimodal fluid delivery device of the present invention may deliver a volume (pre-delivery volume) of drug or vaccine of 0.3mm³ or more at a time, preferably a volume (pre-delivery volume) of 1.0mm³ or more, more preferably a volume (pre-delivery volume) of 5.0mm³ or more, and in some embodiments the volume (pre-delivery volume) of drug or vaccine delivered at a time by the multimodal fluid delivery device of the present invention may reach 14.0mm³, and in further embodiments the volume (pre-delivery volume) of drug or vaccine delivered at a time by the multimodal fluid delivery device of the present invention may reach 46.0mm³.

In some embodiments of the invention, the one or more needle members 210 have different adjustable skin insertion depths.

In some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth that does not substantially insert but that is in intimate contact with human or animal skin.

In some embodiments of the invention, at least one of the one or more needle members 210 has an insertion depth that is substantially inserted into the intradermal layer of a human or animal subject.

In some embodiments of the invention, at least one of the one or more needle members 210 has an insertion depth that is substantially inserted into the subcutaneous layer of a human or animal.

In some embodiments of the invention, at least one of the one or more needle members 210 has an insertion depth that is substantially inserted into a muscle layer of a human or animal.

In some embodiments of the invention, at least one of the one or more needle members 210 has an insertion depth that is substantially inserted into an organ in a human or animal body.

In some embodiments of the present invention, at least one of the one or more needle members 210 has an adjustable depth of insertion.

In some embodiments of the invention, the multi-mode fluid delivery device is configured such that the fluid 130 has a bulk volume in the body that is greater than the undelivered volume, preferably the fluid has a bulk volume in the body that is greater than 1.50 times the undelivered volume, preferably greater than 1.80 times, more preferably greater than 2.40 times, more preferably greater than 3.00 times, still more preferably greater than 3.60 times.

In some embodiments of the invention, the dispersion volume ratio refers to the ratio of the volume of the dispersion region in the body of the fluid delivered via the multi-mode fluid delivery device to the original volume of the fluid not delivered, i.e.:

In other embodiments of the present invention, the dispersion volume ratio may also refer to the ratio of the dispersion volume of a fluid in a body delivered by the multi-mode fluid delivery device of embodiments of the present invention to the dispersion volume of a fluid in a body delivered using manual needle injection, i.e.:

the volume of the dispersed region can be calculated in various ways, for example, in some embodiments of the present invention, a fluorescent marker can be added in advance to the drug or vaccine, and then scanned by a medical imaging technique and the volume of the dispersed region can be calculated using image analysis software, for example, calculating an envelope map of the dispersed region to estimate the volume of the dispersed region.

It will be appreciated that as the delivery fluid enters the body through the multi-mode fluid delivery device, the three-dimensional spatial area of the distribution of the fluid becomes larger due to the diffusion of the fluid within the body, which increases the surface area of the fluid, particularly the drug or vaccine, in contact with the tissue within the body, thereby increasing the bioavailability and efficacy of the drug.

It will be appreciated that one skilled in the art, in light of the teachings of embodiments of the present invention, will be able to ascertain the corresponding dispersion of the dermis, epidermis, subcutaneous, muscle and human organ in the body of an inoculum according to needleless delivery, including but not limited to according to different species of animals, or patients of different physical conditions.

In some embodiments of the invention, as shown in FIGS. 3-6, the needle apertures d of the one or more needle members 210 may be configured such that the fluid jet passing through the one or more needle members 210 has a plurality of different in vivo dispersions, i.e., different dispersion volume ratios, depth of dispersion, or extent of dispersion, whereby in some embodiments of the invention the needle apertures of the one or more needle members 210 may be equal and have a first needle aperture d₁, the first needle aperture d₁ being sized such that the fluid jet passing through the one or more needle members 210 has a different degree of dispersion, preferably a different depth of dispersion, such that the fluid jet is dispersed in at least one of the dermis layer, epidermis layer, subcutaneous layer, muscle, and body organ.

In some embodiments of the present invention, the outlet jet velocity v of the one or more needle members 210 may be configured such that the fluid jet passing through the one or more needle members 210 has a plurality of different in vivo dispersions, i.e., different dispersion volume ratios, depth of dispersion, or extent of dispersion, whereby in some embodiments of the present invention the outlet jet velocity v of the one or more needle members 210 may be equal and have a first outlet jet velocity v₁, the first outlet jet velocity v₁ being sized such that the fluid jet passing through the one or more needle members 210 has a different dispersion, preferably a different depth of dispersion, such that the fluid jet is dispersed in at least one of the dermis, epidermis, subcutaneous, muscle, and human organ.

In some embodiments of the invention, the plurality of needle members includes a first needle member and a second needle member.

In some embodiments of the invention, the first needle member has a first skin insertion depth in one of the dermis layer, epidermis layer, subcutaneous, muscle and human organ and the second needle member has a second skin insertion depth in the other of the dermis layer, epidermis layer, subcutaneous, muscle and human organ. For example, as shown in fig. 7, the skin insertion depths of the one or more needle members 210 may be configured to be unequal, the first needle member 210 having a first skin insertion depth L₁, and the second needle member 210' having a second skin insertion depth L₂, where L₁≠L₂.

In some embodiments of the invention, the first needle member has a first needle aperture sized to disperse a fluid jet through the first needle member in at least one of the dermis, epidermis, subcutaneous, muscle and human organ, and the second needle member has a second needle aperture sized to disperse a fluid jet through the second needle member in at least one other of the dermis, epidermis, subcutaneous, muscle and human organ. For example, as shown in fig. 8, the first needle member 210 has a first needle aperture d₁ and the second needle member 210' has a second needle aperture d₂, where d₁≠d₂.

In some embodiments of the invention, the first needle member has a first outlet jet velocity configured to cause the fluid jet passing through the first needle member to disperse in at least one of the dermis, epidermis, subcutaneous, muscle and human organ, and the second needle member has a second outlet jet velocity configured to cause the fluid jet passing through the second needle member to disperse in at least one other of the dermis, epidermis, subcutaneous, muscle and human organ. For example, the first needle member 210 may have a first outlet jet velocity v₁ and the second needle member 210' may have a second outlet jet velocity v₂, where v₁≠v₂.

In some embodiments of the invention, the plurality of needle members further comprises a third needle member;

in some embodiments of the invention, the third needle member has a third skin insertion depth in a further one of a dermis layer, an epidermis layer, a subcutaneous layer, a muscle and a human organ;

In some embodiments of the invention, the third needle member has a third needle aperture sized such that the fluid jet passing through the third needle member is dispersed in at least one more of the dermis layer, epidermis layer, subcutaneous layer, dermis layer, epidermis layer, or subcutaneous layer of muscle and human organ;

in some embodiments of the invention, the third needle has a third outlet jet velocity configured such that the fluid jet passing through the third needle is dispersed in at least one of the dermis layer, epidermis layer, subcutaneous, muscle and human organ.

In some embodiments of the present invention, as shown in fig. 9-11, the one or more needle members 210 may be aligned in a straight line.

In some embodiments of the present invention, the one or more needle members 210 are aligned along a diameter or a centerline of the injection head 200, and one of the one or more needle members 210 aligned along the diameter or the centerline of the injection head 200 is located at a center or a center of the injection head 200.

In one embodiment of the present invention, as shown in fig. 10, 3 needle members 210 are arranged on the injection head 200 in a straight line along the diameter (center line) of the injection head 200, including the needle member 210' located at the center (center) of the injection head 200.

In some embodiments of the present invention, the plurality of needle members 210 are equally spaced along the line.

In one embodiment of the present invention, as shown in fig. 10 to 11, a plurality of needle members 210 are arranged on the injection head 200 in a straight line along a diameter (center line) of the injection head 200, wherein the plurality of needle members 210 are disposed at equal intervals.

In some embodiments of the present invention, as shown in fig. 9-11, the plurality of needle members 210 aligned along a line are mirror-symmetrical with respect to another diameter or centerline of the injection head 200 that is different from the line.

In some embodiments of the invention, the needle members 210 may have multiple sets, each set of needle members 210 being aligned along a straight line, each set of needle members 210 being aligned along a diameter or a midline of the injection head 200.

In one embodiment of the present invention, as shown in fig. 12, three groups of needle members 210 (in fig. 12 and the following figures, the same group of needle members 210 are shown by dotted lines) are disposed on the injection head 200, wherein each of the groups a and C includes 2 needle members 210 aligned in a straight line, and the group B includes 3 needle members 210 aligned in a straight line.

In some embodiments of the present invention, the plurality of needle members 210 are arranged in an array, and the plurality of needle members 210 in the array are mirror images of each other with respect to first and second mutually perpendicular diameters or midlines of the injection head 200.

In one embodiment of the present invention, as shown in fig. 13, the injection head 200 is provided with 4 needle members 210 arranged in an array (the array relationship of the 4 needle members 210 is shown by the mutually perpendicular dashed lines in fig. 13), and the 4 needle members 210 are respectively mirror-symmetrical with respect to the mutually perpendicular first and second diameters (midlines) of the injection head 200.

In some embodiments of the present invention, the skin insertion depth L 'of the needle member 210' located at the center or center of the injection head 200 is different from the skin insertion depth L of the other needle members 210 of the plurality of needle members 210.

In one embodiment of the present invention, as shown in fig. 7, 3 needle members 210 are arranged on the injection head 200 in a straight line along a diameter (midline) of the injection head 200, including the needle member 210' located at a center (center) of the injection head 200, and a skin insertion depth L ' of the needle member 210' is different from skin insertion depths L of other needle members 210 of the plurality of needle members 210, and in the configuration shown in fig. 7, the L ' > L, it is understood that in other configurations, L ' < L may be configured.

In some embodiments of the present invention, the skin insertion depth L 'of at least one set of needle members 210' of the plurality of sets of needle members 210 is different from the skin insertion depth L of the other sets of needle members 210;

In one embodiment of the present invention, as shown in fig. 14A, the injection head 200 has 2 groups of needle members 210, i.e., group a and group B, arranged in a straight line, wherein the group a and the group B each include 2 needle members 210 'having a skin insertion depth of L', and the group a includes 2 needle members 210 having a skin insertion depth of L ', wherein L' noteql, in the configuration shown in fig. 14A, L '< L, it is understood that in other configurations, L' > L may be configured.

In some embodiments of the present invention, the needle aperture d 'of the needle member 210' located at the center or center of the injection head 200 is different from the needle apertures d of the other needle members 210 of the plurality of needle members 210.

In one embodiment of the present invention, as shown in fig. 15 and 16, the injection head 200 is provided with 3 needle members 210 arranged in a straight line, including a needle member 210' having a needle aperture d ' at the center or circle of the injection head 200, and the remaining two needle members 210 having a needle aperture d, wherein d ' is not equal to d, in the configuration shown in fig. 15, d ' is not equal to d, and d ' is not equal to d in the configurations shown in fig. 8 and 16.

In some embodiments of the present invention, the needle aperture d₂ of at least one set of needle members 210 of the plurality of sets of needle members 210 is different from the needle apertures d₁ of the other sets of needle members 210.

In one embodiment of the present invention, as shown in fig. 17 to 18, three groups of needle members 210, namely, group a, group B and group C, are disposed on the injection head 200, wherein each of the group a and the group C includes 2 needle members 210 aligned along a straight line, and the group B includes 3 needle members 210 'aligned along a straight line, wherein the group B includes 3 needle members 210' having a needle aperture d ', and the group a and the group B includes needle members 210 having a needle aperture d, wherein d' noteqd.

In some embodiments of the present invention, the outlet jet velocity v 'of the needle member 210' located at the center or center of the injection head 200 is different from the outlet jet velocity v of the other needle members 210 of the plurality of needle members 210.

In some embodiments of the invention, the exit jet velocity v₂ of at least one set of needle members 210 of the plurality of sets of needle members 210 is different from the exit jet velocities v₁ of the other sets of needle members 210.

In one embodiment of the present invention, as shown in fig. 17 and 18, three groups of needle members 210 are disposed on the injection head 200, wherein the group a and the group C each include 2 needle members 210 aligned along a line, and the group B includes 3 needle members 210 'aligned along a line, wherein the group B includes 3 needle members 210' having an outlet jet velocity v₂, and the group a and the group C include needle members 210 having an outlet jet velocity v₁, wherein v₂≠v₁.

In some embodiments of the present invention, the plurality of needle members 210 on the injection head 200 are arranged in a ring shape, and the plurality of needle members 210 are arranged in a ring shape with the center or the center of the injection head 200 as the center.

In one embodiment of the present invention, as shown in fig. 19 and 20, fig. 19 shows that 3 needle members 210 are disposed on the injection head 200, the 3 needle members 210 are annularly arranged around the circle center O of the injection head 200, and fig. 20 shows that 4 needle members 210 are disposed on the injection head 200, the 4 needle members 210 are annularly arranged around the circle O of the injection head 200, by way of example.

In some embodiments of the present invention, the needle members 210 have a plurality of sets, each set of needle members 210 being arranged in an annular configuration, the plurality of sets of needle members 210 being arranged in an annular configuration coaxially with one another.

In one embodiment of the present invention, as shown in fig. 21, the injector head 200 is provided with 2 groups of needle assemblies 210, wherein the groups a and B are all arranged in a ring shape and coaxially and annularly arranged with the center O of the injector head 200 as the center of the circle.

In some embodiments of the present invention, at least one of the plurality of needle members 210 in the annular array has a skin insertion depth L' that is different from the other needle members 210.

In some embodiments of the present invention, the skin insertion depth of at least one set of needle members 210 of the plurality of sets of needle members 210 in the annular array is different from the skin insertion depth L of the other sets of needle members 210.

In one embodiment of the present invention, as shown in fig. 14B and 23, the injection head 200 is provided with 2 groups of needle members 210, wherein the groups a and B each include 3 needle members 210, and fig. 14B is a cross-sectional view along the axial direction of the tube 100 of the configuration shown in fig. 23, which shows the skin insertion depths of the plurality of needle members 210 arranged annularly on the injection head, wherein the group a includes 3 needle members 210 having a skin insertion depth L ', the group B includes 3 needle members 210 having a skin insertion depth L', the L '> L is shown in the configuration shown in fig. 14B, and it is understood that L' < L may be provided in another configuration.

In some embodiments of the present invention, the skin insertion depths L of the plurality of sets of needle assemblies 210, which are coaxially and annularly arranged with respect to each other, decrease or increase radially.

In one embodiment of the present invention, referring again to fig. 14B and 23, which illustrate the skin insertion depths of the plurality of needle members 210 in an annular array on the injection head, wherein the group a includes 3 needle members 210 having a skin insertion depth L ' and the group B includes 3 needle members 210 having a skin insertion depth L, the skin insertion depths L of the needle members 210 of the group a and group B are increased radially outwardly, i.e., L ' > L, it will be appreciated that in other configurations, the skin insertion depths L of the needle members 210 of the group a and group B may be decreased radially outwardly, i.e., L ' < L.

In one embodiment of the present invention, referring again to fig. 14B and 23, the injector head 200 is provided with 2 groups of needle members 210, wherein the groups a and B are all annularly arranged and coaxially annularly arranged around the center of the injector head 200, wherein the group a includes 3 needle members 210' having a skin insertion depth L ', the group B includes needle members 210 having a skin insertion depth L, wherein L ' noteql, and wherein in one configuration, the skin insertion depths of the group a needle members 210' and the group B needle members 210 coaxially and annularly arranged with each other are radially and outwardly increasing, i.e., L ' > L, and it is understood that in the other configuration, the skin insertion depths of the group a needle members 210' and the group B needle members 210 may also be provided to be radially and outwardly decreasing, i.e., L ' < L.

In some embodiments of the invention, at least one of the plurality of needle members 210 in the annular array has a needle aperture d' that is different from the other needle members 210;

In some embodiments of the present invention, the needle apertures d' of at least one set of needle members 210 of the plurality of sets of needle members 210 are different from the needle apertures d of the other sets of needle members 210;

In some embodiments of the present invention, the needle apertures d of the plurality of sets of needle assemblies 210, coaxially and annularly arranged with respect to each other, decrease or increase in radial direction.

In one embodiment of the present invention, as shown in fig. 14B and fig. 22 and 23, the injection head 200 is provided with 2 groups of needle members 210, wherein the groups a and B are all arranged in a ring shape and coaxially arranged in a ring shape around the center of the injection head 200, wherein the group B includes 3 needle members 210' having a needle aperture d ', and the group a includes needle members 210 having a needle aperture d, wherein d ' +.d, and in the configuration shown in fig. 22, the needle apertures of the group a needle members 210 and the group B needle members 210' arranged coaxially and annularly to each other decrease radially outward, i.e., d ' > d, and in the configuration shown in fig. 23, the needle apertures of the group a needle members 210 and the group B needle members 210' increase radially outward, i.e., d ' < d.

In some embodiments of the invention, at least one of the needle members 210 in the annular array has an outlet jet velocity v' that is different from the other orifices;

in some embodiments of the present invention, the exit jet velocity v' of at least one set of needle members 210 of the plurality of sets of needle members 210 is different from the exit jet velocities v of the other sets of apertures;

In some embodiments of the present invention, the outlet jet velocity v of the plurality of sets of needle assemblies 210, coaxially and annularly arranged with respect to each other, increases or decreases radially.

In some embodiments of the present invention, the plurality of needle members 210 includes a central needle member 210 "located at the center or center of the injection head 200 and a plurality of peripheral needle members 210 located at the periphery of the central needle member 210.

In one embodiment of the present invention, as shown in fig. 24, the injection head 200 is provided with a central needle member 210″ located at the center (center) of the injection head 200 and 2 peripheral needle members 210 located at the periphery of the central needle member 210.

In some embodiments of the invention, the plurality of peripheral needle members 210 are arranged in an annular array.

In some embodiments of the present invention, the plurality of peripheral needle members 210 are arranged in a coaxial annular array about the central needle member 210 ".

In one embodiment of the present invention, as shown in fig. 24 to 26, a central needle member 210″ located at the center (center) of the injection head 200 and a plurality of peripheral needle members 210 located at the periphery of the central needle member 210 are disposed on the injection head 200, and a configuration in which 4 peripheral needle members 210 are disposed on the injection head 200 is shown in fig. 26 as an example.

In some embodiments of the invention, the peripheral apertures 121 have a plurality of sets, each set of peripheral needle members 210 being arranged in an annular configuration, the plurality of sets of peripheral needle members 210 being arranged in a coaxial annular configuration about the central needle member 210 ".

In one embodiment of the present invention, as shown in fig. 27, the injection head 200 is provided with 6 peripheral needle members 210, the 6 peripheral needle members 210 are divided into two groups A, B uniformly arranged in a ring shape, wherein two groups A, B each include 3 peripheral needle members 210, and the two groups of peripheral needle members 210 are coaxially and annularly arranged around the central needle member 210″.

In some embodiments of the present invention, the skin insertion depth L "of the central needle member 210" is different than the skin insertion depth of the plurality of peripheral needle members 210.

In one embodiment of the present invention, the injector head 200 is provided with 1 central needle piece 210 "having a skin insertion depth of L" and 3 peripheral needle pieces 210 having a skin insertion depth of L, wherein L "is not equal to L, L" < L in one configuration and L "> L in the other configuration.

In some embodiments of the present invention, the skin insertion depth L' of at least one set of peripheral needle members 210 of the plurality of sets of peripheral needle members 210 is different from the skin insertion depth L of the other peripheral sets of needle members 210.

In one embodiment of the invention, the set A contains 3 peripheral needle members 210 having a skin insertion depth of L₁, while the set B contains 3 peripheral needle members 210 having a skin insertion depth of L₂ and L₁≠L₂, L₁＞L₂ in one of the illustrated configurations and L₁＜L₂ in the other configuration.

In some embodiments of the present invention, the skin insertion depth of the plurality of sets of needle members 210 and the central needle member 210 "coaxially and annularly arranged with respect to each other decreases or increases radially.

In one embodiment of the present invention, the 1 center needle member 210 "has a skin insertion depth L", the 3 peripheral needle members 210 of group A have a skin insertion depth L₁, the 3 peripheral needle members 210 of group B have a skin insertion depth L₂, and L₁≠L₂. In one configuration, the skin insertion depths of the A, B groups of needle members 210 and the center needle member 210 "coaxially and annularly arranged with each other decrease radially outward, i.e., L" > L₁＞L₂, and in another configuration, the skin insertion depths of the A, B groups of needle members 210 and the center needle member 210 "coaxially and annularly arranged with each other increase radially, i.e., L" < L₁＜L₂.

In some embodiments of the present invention, the needle aperture d "of the central needle member 210" is different from the needle apertures d of the plurality of peripheral needle members 210.

In one embodiment of the present invention, as shown in fig. 28 to 29, the injection head 200 is provided with 1 central needle member 210 "having a needle aperture d" and 3 peripheral needle members 210 having a needle aperture d, wherein d "is not equal to d, d" < d in the configuration shown in fig. 28, and d "> d in the configuration shown in fig. 29.

In another embodiment of the present invention, as shown in fig. 30 to 32, the injection head 200 is provided with 1 central needle member 210 "having a needle aperture d" and 6 peripheral needle members 210 having a needle aperture d, wherein d "is equal to d, and the 6 peripheral needle members 210 are divided into two groups A, B uniformly arranged in a ring shape, wherein the two groups A, B each include 3 peripheral needle members 210, and the two groups of peripheral needle members 210 are coaxially and annularly arranged around the central needle member 210".

In some embodiments of the present invention, the needle apertures d₁ of at least one set of peripheral needle members 210 of the plurality of sets of peripheral needle members 210 are different from the needle apertures d₂ of the other sets of peripheral needle members 210.

In one embodiment of the present invention, as shown in fig. 31 and 32, wherein the group a contains 3 peripheral needle members 210 having a needle aperture d₁ and the group B contains 3 peripheral needle members 210 having a needle aperture d₂, and the d₁≠d₂, d₁＞d₂ in the configuration shown in fig. 31 and d₁＜d₂ in the configuration shown in fig. 32.

In some embodiments of the present invention, the needle apertures of the plurality of sets of needle members 210 and the central needle member 210 "coaxially and annularly arranged with respect to each other are radially increasing or decreasing.

In one embodiment of the present invention, as shown in FIGS. 31 and 32, wherein the needle aperture of the 1 center needle member 210 "is d", the needle aperture of the 3 peripheral needle members 210 contained in the A group is d₁, and the needle aperture of the 3 peripheral needle members 210 contained in the B group is d₂, and the d₁≠d₂, the needle apertures of the A, B groups of needle members 210 and the center needle member 210 "coaxially and annularly arranged with each other in the configuration shown in FIG. 31 decrease radially outwardly, i.e., d" > d₁＞d₂, and the needle apertures of the A, B groups of needle members 210 and the center needle member 210 "coaxially and annularly arranged with each other in the configuration shown in FIG. 32 increase radially, i.e., d" < d₁＜d₂.

In some embodiments of the present invention, the outlet jet velocity v "of the central needle member 210" is different from the outlet jet velocities v of the plurality of peripheral needle members 210.

In some embodiments of the invention, the exit jet velocity v₁ of at least one set of peripheral needle members 210 of the plurality of sets of peripheral needle members 210 is different from the exit jet velocities v₂ of the other peripheral sets of needle members 210.

In some embodiments of the present invention, the exit jet velocities of the plurality of sets of needle members 210 and the center needle member 210 "coaxially and annularly arranged with each other are radially increased or decreased.

In some embodiments of the present invention, as shown in fig. 33 and 34, the injection head 200 includes a support 220 for supporting the needle member.

In some embodiments of the present invention, the support 220 is configured as a tubular wall extending to one side of the needle cannula 100, while in other embodiments of the present invention, the support 220 may be a separate component from the injector head 200 for connecting the injector head 200 to the tube 100.

In some embodiments of the present invention, as shown in fig. 33 and 34, the needle member 210 further includes a first needle portion 211 located on a side of the support portion 220 opposite the needle tube 100.

In some embodiments of the present invention, as shown in fig. 33 and 34, the needle member 210 includes a fixing pad 230 disposed on a side of the supporting portion 220 facing the needle tube 100, and the fixing pad 230 is used to fix the needle member 210;

In some embodiments of the present invention, as shown in fig. 33 and 34, the needle member 210 includes a second needle portion 212 on a side of the support portion 220 facing the needle tube 100;

In some embodiments of the present invention, fig. 33 and 34 alternatively, the needle member 210 does not extend from the side of the support portion 220 facing away from the needle cannula 100, such that the needle member 210 forms a needleless micropore 213 in the side of the support portion 220 facing away from the needle cannula 100.

In some embodiments of the present invention, the needle member 210 further comprises an interventional soft needle removably connected to the aperture 210.

In some embodiments of the present invention, as shown in fig. 35-37, the multi-mode fluid delivery device further comprises a needle set 400, the needle set 400 comprising a needle sleeve 401 for removably surrounding the first needle portion 211 of the needle 210.

In some embodiments of the present invention, as shown in fig. 35-37, the height h of the needle sleeve 401 of the needle assembly 400 is greater than or equal to the first needle portion 211 of the needle 210, thereby completely surrounding the first needle portion 211;

In some embodiments of the present invention, as shown in fig. 35 to 37, optionally, the needle sleeve 410 of the needle assembly 400 has a height h smaller than the first needle portion 211 of the needle member 210, thereby partially surrounding the first needle portion 211 such that the first needle portion 211 protrudes from the front end of the needle sleeve to form an insertion portion 214.

In some embodiments of the present invention, as shown in fig. 35 to 37, the needle assembly 400 includes a first needle assembly 410, and the height of the needle sleeve 401 of the first needle assembly 410 is greater than the first needle portion 211 of the needle assembly, thereby completely surrounding the first needle portion 211 to protect the first needle portion 211.

In some embodiments of the present invention, as shown in fig. 35-37, the plurality of needle assemblies 400 is a plurality, the plurality of needle assemblies 400 includes a first needle assembly 410 and a second needle assembly 420,

The first needle set 410 is configured such that it surrounds the first needle portion 211 with one of a partially surrounded, insertion site located in the dermis layer, in the epidermis layer, subcutaneously, in the muscle or in the human organ;

The second needle set 420 is configured such that it surrounds the first needle portion 211 with the other of being partially surrounded, inserted in the dermis layer, in the epidermis layer, subcutaneously, in the muscle or in the state of a human organ.

In some embodiments of the invention, the plurality of needle assemblies 400 includes a first needle assembly 410, a second needle assembly 420, a third needle assembly 430, a fourth needle assembly 440, a fifth needle assembly 450, and a sixth needle assembly 460;

The first needle assembly 410 is configured such that it surrounds the first needle portion 211 completely surrounded;

The second needle set 420 is configured such that the insertion portion 214 thereof surrounding the first needle portion 211 is located in the dermis layer;

The third needle set 430 is configured such that the insertion portion 214 thereof surrounding the first needle portion 211 is located in the epidermis layer;

the fourth needle set 440 is configured such that it surrounds the insertion portion 214 of the first needle portion 211 subcutaneously;

the fifth needle set 450 is configured such that it is positioned in the muscle around the insertion portion 214 of the first needle portion 211;

The sixth needle set 460 is configured such that the insertion portion 214 surrounding the first needle portion 211 is located in a human organ.

In some embodiments of the invention, the needle hub structure may be integrated on the injection head. In other embodiments of the present invention, the needle hub structure is axially movable relative to the needle member in the axial direction of the needle member.

In a further embodiment of the invention, the injection head further comprises a needle hub portion sleeved on the needle member and a rotating member operatively connected to the needle member or the needle hub portion, the rotating member being configured to adjust the axial position of the needle member and the needle hub portion by rotation to adjust the exposed length of the needle member relative to the needle hub portion. In some embodiments of the invention, the axial positions of the needle member and the sleeve portion are configured to be adjustable between a plurality of positions such that the exposed length of the needle member is adjustable between a plurality of positions, preferably the exposed length of the needle member is adjustable between a plurality of positions in which the sleeve portion is retracted, flush with the sleeve portion, in the dermis layer, in the epidermis layer, subcutaneously, in the muscle, in the body organ. In some embodiments of the invention, the axial positions of the needle member and the needle hub are configured to be continuously adjustable such that the exposed length of the needle member is continuously adjustable.

In one embodiment of the invention, the injection head comprises a needle sleeve part sleeved on the needle piece and a rotating member operatively connected with the needle piece, a screwing ring and a first thread part are arranged on the rotating member, a second thread part matched with the first thread part is arranged on the needle piece, and the rotating member can adjust the axial position of the needle piece through the rotation of the screwing ring, for example, in one case, the clockwise rotation of the screwing ring can drive the needle piece to extend axially and distally, so that the needle piece extends out of the needle sleeve part sleeved on the needle piece to form an exposed part or adjust the length of the exposed part.

In another embodiment of the invention, the injection head comprises a needle sleeve part sleeved on the needle head piece and a rotating member operatively connected with the needle head piece, wherein a screwing ring and a first thread part are arranged on the rotating member, a second thread part matched with the first thread part is arranged on the needle sleeve part, and the rotating member can adjust the axial position of the needle sleeve part through the rotation of the screwing ring, for example, in one case, the clockwise rotation of the screwing ring can drive the needle sleeve part to extend out axially and distally, so that the needle sleeve part sleeved on the needle head piece covers the top end of the needle head piece to protect the needle head piece.

In a further embodiment of the invention, the injection head comprises a needle sleeve part sleeved on the needle head piece and a rotating component operatively connected with the needle head piece, a screwing ring and a first thread part are arranged on the rotating component, a second thread part matched with the first thread part is arranged on the needle sleeve part, a third thread part matched with the first thread part is arranged on the needle head piece, and the rotating component can adjust the relative axial position of the needle head piece and the needle sleeve part sleeved on the needle head piece through the rotation of the screwing ring.

In the embodiment of the invention, the stepless adjustment of the relative axial positions of the needle head piece and the needle sleeve part sleeved on the needle head piece can be realized through the rotating component, so that the retraction of the needle head piece relative to the needle sleeve part and the stepless adjustment of the exposure or exposure length can be realized.

In some embodiments of the present invention, the injection head 200 includes a connection 240 for detachably connecting the injection head 200 to the tube 100;

in some embodiments of the present invention, as shown in fig. 33 and 34, the connection 240 is a threaded connection;

in some embodiments of the present invention, the connection portion 240 is a clamping portion, and optionally, the connection portion 240 is an adhesive portion.

In some embodiments of the present invention, the multi-mode fluid delivery device further comprises a locking member for locking the injection head 200 to the tube, the locking member comprising a connection portion for detachably connecting the locking member to the tube;

In some embodiments of the invention, the connection is a threaded connection;

in some embodiments of the invention, the connection portion is a clamping portion;

in some embodiments of the invention, the connection is an adhesive.

In some embodiments of the application, any of the multi-mode fluid delivery devices described above in embodiments of the application may also be used in combination with a triple vaccine against cat rhinotracheitis, caliciviropathy, and leukopenia, wherein the triple vaccine is also referred to as a cat triple vaccine. Therefore, the embodiment of the application also provides a corresponding pharmaceutical and mechanical combination product. In embodiments of the application, the pharmaceutical device combination may comprise or may be a drug delivery system.

In the embodiment of the invention, the cat triple vaccine refers to an inactivated vaccine for preventing common infectious diseases of cats, and can prevent cat rhinotracheitis, cat calicivirus diseases and cat leukopenia, wherein the three diseases are the most common infectious diseases of cats, and when the cat triple vaccine is developed, three dominant epidemic strains of the three infectious diseases of the cats are screened from a large number of clinical samples, so that the cat triple vaccine has the characteristics of good safety, rapid antibody production, long immunization duration and one needle for preventing the three diseases. It is suitable for cats over 8 weeks of age and typically requires three-needle vaccination at 8 weeks, 12 weeks and 16 weeks of age for basic immunization. After the basic immunization is completed, one booster needle should be inoculated every year to maintain the immune effect.

In some embodiments of the present invention, the injection head 200 of the multi-mode fluid delivery device used in combination with the cat triple vaccine is provided with 3 holes 121 which are annularly arranged around the center of the injection head 200 at equal intervals, and the distance between the three holes 121 and the center of the injection head 200 is 1.25mm + -20%.

In some embodiments of the invention, the push speed of the plunger 210 of the multi-mode fluid delivery device used in combination with a feline triple vaccine is configured to be 0.12m/s±20%.

In some embodiments of the invention, the multi-mode fluid delivery device used in combination with a cat triple vaccine is configured such that the exit jet velocity of the cat triple vaccine as it is pushed by the plunger 210 out of the bore 121 in the injector head 200 is 150.00m/s ± 20%.

In some embodiments of the invention, the multi-mode fluid delivery device used in combination with the feline triple vaccine is configured such that the dispersion volume of the feline triple vaccine in vivo is greater than 1.5 times the undelivered volume of the feline triple vaccine.

In some embodiments of the invention, the multimodal fluid delivery device used in combination with the feline triple vaccine is configured such that the feline triple vaccine has an average antibody titer that is 1.2 times or more, preferably 2.0 times or more, and even more preferably 4.8 times or more greater than the average antibody titer of the needle injection 14 days after the second dose is vaccinated.

In embodiments of the invention, the average antibody titer is a measure of the intensity of an immune response used to assess the level of antibodies produced by an organism against a particular antigen (e.g., virus, bacteria, or vaccine). It is expressed as the average of the dilution of serum that is capable of neutralizing or binding to a certain amount of antigen under a specific condition. In other words, a higher average antibody titer indicates a greater ability of an organism to produce antibodies against a particular pathogen.

In some embodiments of the invention, the multimodal fluid delivery device used in combination with the feline triple vaccine is configured such that the feline triple vaccine has an average antibody titer that is 1.2 times or more, preferably 2.0 times or more, and more preferably 3.7 times or more greater than the average antibody titer of the needle injection 30 days after the second dose is administered.

In some embodiments of the invention, the multimodal fluid delivery device used in combination with the feline triple vaccine is configured such that the feline triple vaccine has an average antibody titer that is 1.2 times or more, preferably 2.0 times or more, and more preferably 6.3 times or more the average antibody titer of the needle injection 60 days after the second dose is vaccinated.

In some embodiments of the invention, the multimodal fluid delivery device used in combination with the feline triple vaccine is configured such that the feline triple vaccine has an average antibody titer over 60 days after the second dose of 60% vaccine dose administration that is 1.1 times or more, preferably 1.5 times or more, and more preferably 2.0 times or more the average antibody titer produced by the needle injection of 100% vaccine dose.

In some embodiments of the application, any of the multi-mode fluid delivery devices described above in embodiments of the application may also be used in combination with a hepatitis B vaccine. Therefore, the embodiment of the application also provides a corresponding pharmaceutical and mechanical combination product. In embodiments of the application, the pharmaceutical device combination may comprise or may be a drug delivery system.

In the embodiment of the invention, the hepatitis B vaccine refers to a hepatitis B recombinant yeast vaccine (hansenula polymorpha) for preventing hepatitis B (a viral liver disease), which is prepared by purifying hepatitis B virus surface antigen (HBsAg) expressed by recombinant hansenula polymorpha and adding an aluminum adjuvant, wherein the active ingredient is the hepatitis B virus surface antigen. The vaccine is suitable for hepatitis B patients, especially for neonates, especially for mothers who are positive for HBsAg and HBeAg, for hepatitis B patients aged 16 years and over 16 years, for medical staff and for blood-contacting laboratory staff. After vaccination, the immune system can be stimulated to produce protective antibodies, so that the human body has the immunity of preventing hepatitis B, and the aim of preventing hepatitis B infection is fulfilled. The conventional immunization site is the upper arm deltoid intramuscular injection. Immunization procedure was 3 needles, vaccinated once at birth (0 month), 1-2 months of age and 6-18 months of age, respectively, and neonates were injected with 1 st needle, 1 dose each time, within 24 hours after birth.

In some embodiments of the present invention, the injection head 200 of the multi-mode fluid delivery device used in combination with hepatitis B vaccine is provided with 3 holes 121 which are annularly arranged around the center of the injection head 200 at equal intervals, and the distance between the three holes 121 and the center of the injection head 200 is 1.25mm + -20%.

In some embodiments of the invention, the push speed of the plunger 210 of a multi-mode fluid delivery device used in combination with a hepatitis B vaccine is configured to be 0.12 m/s.+ -. 20%.

In some embodiments of the present invention, the multi-mode fluid delivery device used in combination with a hepatitis B vaccine is configured such that the exit jet velocity of the hepatitis B vaccine as it is pushed by the plunger 210 out of the bore 121 in the injector head 200 is 150.00 m/s.+ -. 20%.

In some embodiments of the invention, the multi-mode fluid delivery device used in combination with a hepatitis B vaccine is configured such that the dispersion volume of the hepatitis B vaccine in vivo is greater than 1.5 times the undelivered volume of the hepatitis B vaccine.

In some embodiments of the invention, the multimodal fluid delivery device used in combination with a hepatitis B vaccine is configured such that the average antibody titer after 14 days of vaccination of the second dose of hepatitis B vaccine is 1.1 times or more, preferably 1.5 times or more, still preferably 2.0 times or more the average antibody titer of the needle injection.

In some embodiments of the invention, the multimodal fluid delivery device used in combination with a hepatitis B vaccine is configured such that the average antibody titer after 42 days of vaccination of the hepatitis B vaccine is 1.1 times or more, preferably 1.5 times or more, still preferably 2.0 times or more the average antibody titer of the needle injection.

In some embodiments of the invention, the multimodal fluid delivery device used in combination with a hepatitis B vaccine is configured such that the average antibody titer 42 days after the injection of the second dose of 60% vaccine dose is greater than 1.1 times, preferably greater than 1.3 times, and even more preferably greater than 1.5 times the average antibody titer produced by the needle injection of the 100% vaccine dose.

In some embodiments of the invention, the multi-mode fluid delivery device used in combination with the hepatitis B vaccine is configured such that the positive expression rate of T lymphocytes is greater than 10%, preferably greater than 20%, and more preferably greater than 50% after 42 days of vaccination with the second dose of hepatitis B vaccine.

In some embodiments of the application, any of the multi-mode fluid delivery devices described above in embodiments of the application may also be used in combination with a human pneumonic vaccine. Therefore, the embodiment of the application also provides a corresponding pharmaceutical and mechanical combination product. In embodiments of the application, the pharmaceutical device combination may comprise or may be a drug delivery system.

In some embodiments of the present invention, the injection head 200 of the multi-mode fluid delivery device used in combination with the pneumonia vaccine for human is provided with 3 holes 121 which are annularly arranged around the center of the injection head 200 at equal intervals, and the distance between the three holes 121 and the center of the injection head 200 is 1.25mm + -20%.

In some embodiments of the invention, the push speed of the plunger 210 of the multi-mode fluid delivery device used in combination with a human pneumonitis vaccine is configured to be 0.14m/s + -20%.

In some embodiments of the invention, the multi-mode fluid delivery device used in combination with a human pneumonitis vaccine is configured such that the exit jet velocity of the human pneumonitis vaccine as it is pushed away from the bore 121 in the injection head 200 by the plunger 210 is 160.00m/s ± 20%.

In some embodiments of the invention, the multi-mode fluid delivery device used in combination with the human pneumonic vaccine is configured such that the dispersion volume of the human pneumonic vaccine in the body is more than 1.5 times the undelivered volume of the human pneumonic vaccine.

In some embodiments of the invention, the multimodal fluid delivery device used in combination with a human pneumonic vaccine is configured such that the human pneumonic vaccine has an average antibody titer after vaccination that is 1.1 times or more, preferably 1.5 times or more, still preferably 2.0 times or more the average antibody titer of the needle injection.

In some embodiments of the invention, the multimodal fluid delivery device used in combination with the human pneumonic vaccine is configured such that the average antibody titer after 42 days of vaccination of the human pneumonic vaccine is 1.1 times or more, preferably 1.5 times or more, still preferably 2.0 times or more the average antibody titer of the needle injection.

In some embodiments of the invention, the multimodal fluid delivery device used in combination with a human pneumonic vaccine is configured such that the mean antibody titer after injection of 60% vaccine dose vaccination is 1.1 times or more, preferably 1.3 times or more, still preferably 1.5 times or more the mean antibody titer resulting from injection of 100% vaccine dose with a needle.

In some embodiments of the application, any of the multi-mode fluid delivery devices described above in embodiments of the application may also be used in combination with a GLP-1 class polypeptide. Therefore, the embodiment of the application also provides a corresponding pharmaceutical and mechanical combination product. In embodiments of the application, the pharmaceutical device combination may comprise or may be a drug delivery system.

In some embodiments of the present invention, the injector head 200 of the multi-mode fluid delivery device used in combination with GLP-1 type polypeptides is provided with three holes 121, the three holes 121 being annularly arranged at equal intervals around the center of the injector head 200, the three holes being 1.25mm ± 20% from the center.

In some embodiments of the invention, the plunger 210 of a multi-mode fluid delivery device used in combination with a GLP-1 type polypeptide has a push speed of 0.16m/s±20%;

In some embodiments of the invention, the multi-mode fluid delivery device used in combination with a GLP-1 class polypeptide is configured such that the outlet jet velocity of the GLP-1 class polypeptide as it is pushed by the plunger 210 out of the bore 121 in the injector head 200 is 170.00m/s±20%.

In some embodiments of the invention, the multi-mode fluid delivery device used in combination with a GLP-1 class polypeptide is configured such that the in vivo dispersion volume of the GLP-1 class polypeptide is greater than 1.5 times the undelivered volume of the GLP-1 class polypeptide.

In some embodiments of the application, the GLP-1 type polypeptide comprises semaglutin, and any of the multi-mode fluid delivery devices described in the embodiments of the application above may be used in combination with semaglutin. Therefore, the embodiment of the application also provides a corresponding pharmaceutical and mechanical combination product. In embodiments of the application, the pharmaceutical device combination may comprise or may be a drug delivery system.

In some embodiments of the invention, the semaglutin (Simeigelutai), also known as Soxhlet Ma Lutai, is a second generation glucagon-like peptide-1 (GLP-1) analog with a molecular formula of C₁₈₇H₂₉₁N₄₅O₅₉ (molecular weight of 4113.58 Da), has excellent hypoglycemic and weight-reducing effects on diabetics, is obviously superior to sitagliptin, insulin glargine U100 or slow-release exenatide, and is also superior to the cognate medicament liraglutide in weight loss, particularly in patients with BMI not less than 30. The semaglutin can be administered orally or subcutaneously, for example, in an oral dosage form of 7mg/14mg once a day or in a subcutaneous dosage form of 0.5mg/1.0mg once a week. The semaglutin has good curative effect in diabetes treatment, and has obvious advantages in aspects of weight reduction and cardiovascular protection.

In some embodiments of the invention, the multi-mode fluid delivery device used in combination with the semaglutin is configured such that the diffuse volume of the semaglutin in the body is greater than 1.5 times the undelivered volume of the semaglutin.

In some embodiments of the invention, the multi-mode fluid delivery device used in combination with semaglutin is configured such that the reducing effect of semaglutin on human and animal body weight is consistent with a needle injection, preferably the reducing effect is improved by 2%, more preferably by 5%, still more preferably by 10% over a needle injection.

In some embodiments of the invention, the multi-mode fluid delivery device used in combination with semaglutin is configured such that the end point of weight loss of semaglutin in vivo is consistent with a needle injection, preferably by more than 2%, more preferably by more than 5%, still more preferably by more than 10%.

In some embodiments of the invention, the multi-mode fluid delivery device used in combination with semaglutin is configured such that the ratio of adverse effects of semaglutin causing nausea, vomiting, abdominal distention, etc. is consistent with a needle injection, preferably reduced by more than 5%, more preferably by more than 10%, still more preferably by more than 20%.

In some embodiments of the application, any of the multi-mode fluid delivery devices of the embodiments of the application may also be used in combination with a pharmaceutical formulation. Therefore, the embodiment of the application also provides a corresponding pharmaceutical and mechanical combination product. In embodiments of the application, the pharmaceutical device combination may comprise or may be a drug delivery system.

In some embodiments of the invention, the pharmaceutical formulation is a rabies vaccine for human use.

In some embodiments of the invention, the pharmaceutical formulation is a rabies vaccine for animals.

In some embodiments of the invention, the pharmaceutical formulation is a meningitis vaccine for humans.

In some embodiments of the invention, the pharmaceutical formulation is a hand-foot-and-mouth disease vaccine for animals.

In some embodiments of the invention, the pharmaceutical formulation is a novel human crown vaccine.

In some embodiments of the invention, the pharmaceutical formulation is a human hepatitis a vaccine.

In some embodiments of the invention, the pharmaceutical formulation is a human kidney syndrome hemorrhagic fever vaccine.

In some embodiments of the invention, the pharmaceutical formulation is a mumps vaccine for human use.

In some embodiments of the invention, the pharmaceutical formulation is an HPV vaccine for human use.

In some embodiments of the invention, the pharmaceutical formulation is a tumor chemotherapeutic for human use.

In some embodiments of the invention, the pharmaceutical formulation is a human oncology drug therapy.

In some embodiments of the invention, the pharmaceutical formulation is a tumor vaccine for humans, including but not limited to a polypeptide vaccine, an mRNA vaccine, a DNA vaccine.

In some embodiments of the invention, the pharmaceutical formulation is a porcine diarrhea bivalent vaccine. In some embodiments of the invention, the porcine diarrhea bivalent vaccine may comprise porcine transmissible gastroenteritis, porcine epidemic diarrhea bivalent live vaccine (HB 08 strain+zj08 strain). In some embodiments of the invention, the porcine diarrhea bivalent vaccine may comprise porcine transmissible gastroenteritis, porcine epidemic diarrhea bivalent inactivated vaccine.

In some embodiments of the invention, the pharmaceutical formulation is a blue-ear inactivated vaccine. In some embodiments of the invention, the blue-ear inactivated vaccine may comprise a porcine reproductive and respiratory syndrome inactivated vaccine (CH-1 a strain).

In some embodiments of the invention, the pharmaceutical formulation is a foot and mouth disease vaccine. In some embodiments of the invention, the foot-and-mouth disease vaccine may be for pigs, cattle or sheep. In some embodiments of the invention, the foot-and-mouth disease vaccine may comprise a porcine foot-and-mouth disease type O inactivated vaccine (O/Mya 98/XJ/2010 strain +O/GX/09-7 strain). In some embodiments of the invention, the foot-and-mouth disease vaccine may comprise a porcine foot-and-mouth disease type O, A bivalent inactivated vaccine (Re-O/MYA 98/JSCZ/2013 strain +Re-A/WH/09 strain). In some embodiments of the invention, the foot-and-mouth disease vaccine may comprise a foot-and-mouth disease type O inactivated vaccine (OJMS strain), which may be used in cattle or sheep. In some embodiments of the invention, the foot-and-mouth disease vaccine may comprise a foot-and-mouth disease type O, A bivalent inactivated vaccine (O/HB/HK/99 strain+AF/72 strain, suspension culture), which may be used in cattle. In some embodiments of the invention, the foot-and-mouth disease vaccine may comprise a foot-and-mouth disease type O, type a bivalent inactivated vaccine (O/MYA 98/BY/2010 strain + Re-a/WH/09 strain), which may be used in cattle or sheep.

In some embodiments of the invention, the pharmaceutical formulation is a bovine bivalent vaccine. In some embodiments of the invention, the bovine bivalent vaccine may comprise bovine viral diarrhea/mucosal disease, infectious rhinotracheitis bivalent inactivated vaccine (NMG strain + LY strain).

In some embodiments of the invention, the pharmaceutical formulation is a papanicolaou vaccine. In some embodiments of the invention, the pap mann vaccine may comprise an inactivated vaccine against bovine pasteurellosis.

In some embodiments of the invention, the pharmaceutical formulation is islets.

In some embodiments of the invention, the pharmaceutical formulation is a botulinum-type cosmetic medicament for medical cosmetology.

In some embodiments of the present invention there is also provided a needle-free needle cannula for a multi-mode fluid delivery device of any of the above embodiments of the present invention comprising a tube 100 for containing a fluid, the tube 100 having a first end 110 and a second end 120, wherein the first end 110 is configured and adapted to receive a plunger 210 for pushing the fluid 130, and the second end 120 has a plurality of apertures 121 for distributing the fluid 130 within the tube.

In some embodiments of the present invention, as shown in fig. 38-39, the second end 120 of the needleless delivery device may further have a narrowing section 122 that tapers distally from the tube 100 axially, and a hole 124 is provided in an end face 123 of the narrowing section 122. The end face 123 is configured in a circular shape.

In some embodiments of the invention, the total fluid delivery area of the plurality of apertures of the needle-free needle cannula is 0.009mm² or more, preferably 0.02mm² or more, more preferably 0.053mm², more preferably 0.2800mm² or more, and the single aperture area of the apertures is 0.0028 to 0.035mm², preferably 0.0028 to 0.020mm², more preferably 0.0028 to 0.009mm².

In some embodiments of the invention, the needle-free needle cannula is configured such that fluid jets through the plurality of apertures 121 have different in vivo dispersions;

In other embodiments of the present invention, the dispersion refers to a comprehensive concept describing the in vivo distribution characteristics of a fluid, and in particular, the dispersion may include, but is not limited to, the dispersion volume ratio, the depth of dispersion, the center of dispersion, and the fringe liquid distribution density of the fluid.

In some embodiments of the invention, the apertures of the plurality of apertures 121 of the needle-free needle cannula are configured such that the fluid jets passing through the plurality of apertures 121 have different in vivo dispersions.

In some embodiments of the present invention, the plurality of apertures 121 of the needle-free cannula comprises a first aperture 121;

In some embodiments of the invention, the first aperture 121 has a first aperture d₁, the first aperture d₁ being sized such that the fluid jet passing through the first aperture 121 is dispersed in at least one of the dermis, epidermis, subcutaneous, muscle and human organ.

In some embodiments of the present invention, the plurality of apertures 121 of the needle-free needle cannula includes a first aperture 121 and a second aperture 121';

In some embodiments of the invention, the first aperture 121 has a first aperture d₁ sized to disperse the fluid jet through the first aperture 121 in at least one of the dermis, epidermis, subcutaneous, muscle and human organ, and the second aperture 121 'has a second aperture d₂ sized to disperse the fluid jet through the second aperture 121' in at least one other of the dermis, epidermis, subcutaneous, muscle and human organ.

In some embodiments of the present invention, the plurality of holes 121 of the needle-free tube are arranged in a straight line;

In some embodiments of the present invention, the plurality of holes 121 are aligned along a diameter or a center line of the second end 120, and preferably, one of the plurality of holes 121 aligned along a diameter or a center line of the second end 120 is located at a center or a center of the second end 120;

In some embodiments of the present invention, the plurality of holes 121 arranged in a straight line are equally spaced;

In some embodiments of the invention, the plurality of holes 121 aligned in a straight line are mirror symmetrical with respect to a diameter or midline of the second end 120;

in some embodiments of the invention, the holes 121 have multiple sets, each set of holes 121 being aligned along a straight line, preferably each set of holes being aligned along a diameter or a midline of the second end 120;

In some embodiments of the present invention, the plurality of holes 121 are arranged in an array, the plurality of holes 121 in the array being mirror-symmetrical with respect to first and second mutually perpendicular diameters or centerlines of the second end 120, respectively;

In some embodiments of the invention, the aperture d of the hole 121 at the center or center of the second end 120 is different from the aperture d 'of the other holes 121' of the plurality of holes 121;

In some embodiments of the invention, the apertures of at least one set of apertures 121 in the plurality of sets of apertures 121 are different from the apertures of the other sets of apertures.

In some embodiments of the present invention, the plurality of apertures 121 of the needle-free cannula are arranged in an annular configuration;

In some embodiments of the present invention, the plurality of holes 121 are annularly arranged with respect to the center or circle of the second end 120;

the holes 121 have a plurality of groups, each group of holes 121 being arranged in an annular shape, preferably the plurality of groups of holes 121 being arranged in an annular shape coaxially with each other;

In some embodiments of the invention, at least one of the plurality of holes 121 in the annular array has a different pore size than the other holes 121;

In some embodiments of the invention, the apertures of at least one set of apertures 121 of the plurality of sets of apertures 121 are different from the apertures of the other sets of apertures;

in some embodiments of the present invention, the apertures of the plurality of sets of holes 121 coaxially and annularly arranged with each other are radially increased or decreased.

In some embodiments of the present invention, the plurality of holes of the needle-free needle cannula include a center hole 121″ located at the center or center of the second end 120 and a plurality of peripheral holes 121 located at the periphery of the center hole;

in some embodiments of the present invention, the plurality of peripheral holes 121 are arranged in an annular shape, preferably, the plurality of peripheral holes 121 are arranged in a coaxial annular shape around the central hole 121″;

The peripheral holes 121 have a plurality of sets, each set of peripheral holes 121 being arranged in an annular pattern, preferably the plurality of sets of peripheral holes 121 being arranged in a coaxial annular pattern about the central hole 121 ".

In some embodiments of the invention, the aperture d "of the central aperture 121" is different from the aperture d of the plurality of peripheral apertures 121.

In some embodiments of the present invention, there is also provided an injection head 200 for a multi-mode fluid delivery device, the injection head 200 comprising one or more needle members 210, and a support 220 for supporting the needle members 210.

In some embodiments of the invention, the support 220 has a first side 221 and a second side 222 opposite the first side 221;

optionally, the needle 210 comprises a first needle portion 211 at a first side 221 of the support 220;

Optionally, the needle 210 comprises a fixing pad 230 located at the first side 221 of the supporting part 220, and the fixing pad 230 is used for fixing the needle 210;

optionally, the needle member 210 includes a second needle portion 212 on a second side 222 of the support portion 220;

In some embodiments of the present invention, alternatively, the first needle portion 211 of the needle 210 does not extend from the first side 221 of the support portion 220, such that the first side 221 of the support portion 220 forms the needleless microwells 213.

In some embodiments of the present invention, the first needle portion 211 of the needle 210 is flat and the second needle portion 212 of the needle 210 is sharp.

In some embodiments of the present invention, both the first tip segment 211 and the second tip segment 212 of the needle 210 are sharp.

In some embodiments of the present invention, the one or more needle members 210 have different adjustable skin insertion depths L;

in some embodiments of the present invention, at least one of the one or more needle members 210 has an insertion depth that does not substantially insert but that is in intimate contact with human or animal skin.

In some embodiments of the invention, at least one of the one or more needle members 210 has an insertion depth that is substantially inserted into the intradermal layer of a human or animal subject.

In some embodiments of the invention, at least one of the one or more needle members 210 has an insertion depth that is substantially inserted into the subcutaneous layer of a human or animal.

In some embodiments of the invention, at least one of the one or more needle members 210 has an insertion depth that is substantially inserted into a muscle layer of a human or animal.

In some embodiments of the invention, at least one of the one or more needle members 210 has an insertion depth that is substantially inserted into an organ in a human or animal body.

In some embodiments of the invention, at least one of the one or more needle members has an adjustable depth of insertion.

It will be appreciated that in embodiments of the present invention, the dermis layer, epidermis layer, subcutaneous, muscle or human organ corresponds to not a certain exact, fixed insertion depth value, nor a certain exact, fixed insertion depth value range, and those skilled in the art will be able to identify the corresponding insertion depth of the dermis layer, epidermis layer, subcutaneous, muscle and human organ in the body of the inoculated body from a needleless delivered inoculated body, including but not limited to from different species of animal, or different physical conditions of the patient.

In some embodiments of the present invention, the plurality of needle members 210 comprises a first needle member;

In some embodiments of the present invention, the needle apertures of the one or more needle members 210 may be equal and have a first needle aperture d₁, the first needle aperture d₁ being sized such that the fluid jet passing through the one or more needle members 210 has different dispersion, preferably different depth of dispersion, such that the fluid jet is dispersed in at least one of the dermis layer, epidermis layer, subcutaneous, muscle and body organ.

In some embodiments of the present invention, the plurality of needle members 210 includes a first needle member 210 and a second needle member 210';

in some embodiments of the present invention, the first needle member 210 has a first skin insertion depth in one of the dermis layer, epidermis layer, subcutaneous, muscle and human organ, and the second needle member 210' has a second skin insertion depth in the other of the dermis layer, epidermis layer, subcutaneous, muscle and human organ;

In some embodiments of the invention, the first needle member 210 has a first needle aperture d sized to disperse a fluid jet through the first needle member 210 in at least one of the dermis, epidermis, subcutaneous, muscle and human organ, and the second needle member 210' has a second needle aperture d ' sized to disperse a fluid jet through the second needle member 210' in at least one other of the dermis, epidermis, subcutaneous, muscle and human organ.

In other embodiments of the present invention, the plurality of needle members further preferably includes a third needle member 210", preferably the third needle member 210" has a third skin insertion depth in one of the dermis layer, epidermis layer, subcutaneous, muscle and human organ.

In some embodiments of the present invention, the plurality of needle members 210 are arranged in a straight line;

in some embodiments of the present invention, the plurality of needle members 210 are aligned along a diameter or a center line of the injection head, and preferably, one of the plurality of needle members 210 aligned along a diameter or a center line of the injection head 200 is located at a center or a center of the injection head 200;

in some embodiments of the present invention, the plurality of needle members 210 are disposed at equal intervals along a straight line;

In some embodiments of the present invention, the plurality of needle 210 pieces aligned in a straight line are mirror images of the diameter or midline of the injector head 200;

in some embodiments of the invention, the needle members 210 have multiple sets, each set of needle members 210 being aligned along a straight line, preferably each set of needle members 210 being aligned along a diameter or a midline of the injection head;

The plurality of needle members 210 are arranged in an array, and preferably the plurality of needle members 210 in an array are each mirror-symmetrical about first and second mutually perpendicular diameters or centerlines of the end face of the injection head 200.

In some embodiments of the present invention, the skin insertion depth L "of the needle member 210" located at the center or center of the injection head 200 is different from the skin insertion depth L of the other needle members of the plurality of needle members 210;

preferably, the skin insertion depth L' of at least one of the plurality of sets of needle members 210 is different from the skin insertion depth L of the other sets of needle members 210;

preferably, the needle aperture d "of the needle member 210" located at the center or center of the injection head 200 is different from the needle apertures d of the other needle members 210 of the plurality of needle members 210;

preferably, the needle apertures d 'of at least one set of needle members 210' of the plurality of sets of needle members 210 are different from the needle apertures d of the other sets of needle members.

In some embodiments of the invention, the plurality of needle members 210 are arranged in an annular configuration;

In some embodiments of the present invention, the plurality of needle members 210 are annularly arranged around the center or circle of the injection head 200;

The needle members 210 have a plurality of sets, each set 210 being arranged in an annular pattern, preferably the plurality of sets 210 being arranged in an annular pattern coaxially with one another.

In some embodiments of the present invention, at least one of the plurality of needle members 210 in the annular array has a skin insertion depth L' that is different from the other needle members 210.

In some embodiments of the present invention, the skin insertion depth L 'of at least one set of needle members 210' of the plurality of sets of needle members 210 is different from the skin insertion depth L of the other sets of needle members.

In some embodiments of the present invention, the skin insertion depths L of the plurality of sets of needle assemblies 210, which are coaxially and annularly arranged with respect to each other, decrease or increase radially.

In some embodiments of the present invention, at least one of the plurality of needle members 210 in the annular array has a needle aperture d' that is different from the other needle members 210.

In some embodiments of the present invention, the needle apertures d 'of at least one set of needle members 210' of the plurality of sets of needle members 210 are different from the needle apertures d of the other sets of needle members 210.

In some embodiments of the present invention the needle apertures d of the plurality of sets of needle assemblies 210, which are coaxially and annularly arranged with respect to each other, decrease or increase in radial direction.

In some embodiments of the present invention, the plurality of needle members 210 includes a central needle member 210 "located at the center or center of the injection head 200 and a plurality of peripheral needle members 210 located at the periphery of the central needle member 210";

in some embodiments of the present invention, the plurality of peripheral needle members 210 are arranged in an annular array, preferably the plurality of peripheral needle members 210 are arranged in a coaxial annular array around the central needle member 210 ";

the peripheral needle members have a plurality of sets, each set of peripheral needle members 210 being arranged in an annular pattern, preferably the plurality of sets of peripheral needle members 210 being arranged in a coaxial annular pattern about the central needle member 210 ".

In some embodiments of the present invention, the skin insertion depth L "of the central needle member 210" is different from the skin insertion depth L of the plurality of peripheral needle members 210;

In some embodiments of the present invention, the skin insertion depth L 'of at least one set of peripheral needle members 210' of the plurality of sets of peripheral needle members 210 is different from the skin insertion depth L of the other peripheral sets of needle members 210;

In some embodiments of the present invention, the skin insertion depth of the plurality of sets of needle members 210 and the central needle member 210 "coaxially and annularly arranged with respect to each other decreases or increases radially;

Preferably, the needle aperture d "of the central needle member 210" is different from the needle apertures d of the plurality of peripheral needle members 210;

In some embodiments of the present invention, the needle apertures d 'of at least one set of peripheral needle members 210' of the plurality of sets of peripheral needle members 210 are different from the needle apertures d of the other peripheral sets of needle members 210;

in some embodiments of the present invention, the needle apertures of the plurality of sets of needle members 210 and the central needle member 210 "coaxially and annularly arranged with respect to each other are radially increasing or decreasing.

In some embodiments of the invention, the needle member 210 further comprises an interventional soft needle removably connected to the aperture.

In some embodiments of the present invention, there is also provided a needle set 400 for a multi-mode fluid delivery device, the needle set 400 comprising one or more needle sleeves 401, wherein the needle sleeves 401 are configured to removably enclose the first needle portion 211 of the needle member 210.

In some embodiments of the present invention, the needle sleeve 401 has a height greater than or equal to the first needle portion 211 of the needle member 210, thereby completely surrounding the first needle portion 211;

in some embodiments of the invention, the needle sleeve 401 of the needle set has a height that is less than the first needle portion 211 of the needle member 210, thereby partially surrounding the first needle portion 211 such that the first needle portion 211 protrudes from the front end of the needle sleeve 401 to form an insertion portion 214.

In some embodiments of the invention, the needle assembly 400 comprises a first needle assembly 410, the needle sleeve 401 of the first needle assembly 410 having a height greater than the first needle portion 211 of the needle assembly, thereby completely surrounding the first needle portion 211 to protect the first needle portion 211.

In some embodiments of the present invention, the plurality of needle assemblies 400 is a plurality, preferably, the plurality of needle assemblies 400 includes a first needle assembly 410 and a second needle assembly 420,

The first needle set 410 is configured such that it surrounds the first needle portion 211 with one of a partially surrounded, insertion site located in the dermis layer, in the epidermis layer, subcutaneously, in the muscle or in the human organ;

The second needle set 420 is configured such that it surrounds the first needle portion 211 with the other of being partially surrounded, inserted in the dermis layer, in the epidermis layer, subcutaneously, in the muscle or in the state of a human organ.

In some embodiments of the invention, the number of needle assemblies is 400 or more, preferably the number of needle assemblies includes a first needle assembly 410, a second needle assembly 420, a third needle assembly 430, a fourth needle assembly 440, a fifth needle assembly 450, and a sixth needle assembly 460;

The first needle assembly 410 is configured such that it surrounds the first needle portion 211 completely surrounded;

The second needle set 420 is configured such that the insertion portion 214 thereof surrounding the first needle portion 211 is located in the dermis layer;

The third needle set 430 is configured such that the insertion portion 214 thereof surrounding the first needle portion 211 is located in the epidermis layer;

the fourth needle set 440 is configured such that it surrounds the insertion portion 214 of the first needle portion 211 subcutaneously;

the fifth needle set 450 is configured such that it is positioned in the muscle around the insertion portion 214 of the first needle portion 211;

The sixth needle set 460 is configured such that the insertion portion 214 surrounding the first needle portion 211 is located in a human organ.

In some embodiments of the invention, the injection head further comprises a needle hub portion sleeved on the needle member and a rotating member operatively connected to the needle member or the needle hub portion, the rotating member being configured to adjust the axial position of the needle member and the needle hub portion by rotation to adjust the exposed length of the needle member relative to the needle hub portion.

In some embodiments of the invention, the axial positions of the needle member and the sleeve portion are configured to be adjustable between a plurality of positions such that the exposed length of the needle member is adjustable between a plurality of positions, preferably the exposed length of the needle member is adjustable between a plurality of positions in which the sleeve portion is retracted, flush with the sleeve portion, in the dermis layer, in the epidermis layer, subcutaneously, in the muscle, in the body organ.

In some embodiments of the invention, the axial positions of the needle member and the needle hub are configured to be continuously adjustable such that the exposed length of the needle member is continuously adjustable.

In some embodiments of the present invention, there is also provided the use of a multi-mode fluid delivery device according to any of the above embodiments of the present invention in the manufacture of a medicament for use in human clinical medicine and animal health care for needleless injection administration.

In some embodiments of the invention, the pharmaceutical formulation is a feline triple vaccine.

In some embodiments of the invention, the pharmaceutical formulation is a hepatitis b vaccine.

In some embodiments of the invention, the pharmaceutical formulation is a pneumonic vaccine for humans.

In some embodiments of the invention, the pharmaceutical formulation is semaglutin.

In some embodiments of the invention, the pharmaceutical formulation is a rabies vaccine for human use.

In some embodiments of the invention, the pharmaceutical formulation is a rabies vaccine for animals.

In some embodiments of the invention, the pharmaceutical formulation is a meningitis vaccine for humans.

In some embodiments of the invention, the pharmaceutical formulation is a hand-foot-and-mouth disease vaccine for animals.

In some embodiments of the invention, the pharmaceutical formulation is a novel human crown vaccine.

In some embodiments of the invention, the pharmaceutical formulation is a human hepatitis a vaccine.

In some embodiments of the invention, the pharmaceutical formulation is a human kidney syndrome hemorrhagic fever vaccine.

In some embodiments of the invention, the pharmaceutical formulation is a mumps vaccine for human use.

In some embodiments of the invention, the pharmaceutical formulation is an HPV vaccine for human use.

In some embodiments of the invention, the pharmaceutical formulation is a tumor chemotherapeutic for human use.

In some embodiments of the invention, the pharmaceutical formulation is a human oncology drug therapy.

In some embodiments of the invention, the pharmaceutical formulation is a tumor vaccine for humans, including but not limited to a polypeptide vaccine, an mRNA vaccine, a DNA vaccine.

In some embodiments of the invention, the pharmaceutical formulation is a porcine diarrhea bivalent vaccine.

In some embodiments of the invention, the pharmaceutical formulation is a blue-ear inactivated vaccine.

In some embodiments of the invention, the pharmaceutical formulation is a foot and mouth disease vaccine.

In some embodiments of the invention, the pharmaceutical formulation is a bovine bivalent vaccine.

In some embodiments of the invention, the pharmaceutical formulation is a papanicolaou vaccine.

In some embodiments of the invention, the pharmaceutical formulation is insulin.

In some embodiments of the invention, the pharmaceutical formulation is a botulinum-type cosmetic medicament for medical cosmetology.

In some embodiments of the present invention, there is also provided a method of delivering a multi-mode pharmaceutical formulation, characterized by:

Determining a drug formulation delivery mode according to the acquired preset information, wherein the delivery mode comprises a first delivery mode and a second delivery mode;

when determining a first delivery mode, needlelessly delivering the pharmaceutical formulation through a perforated tube, and determining a first delivery parameter of needleless delivery according to the preset information, wherein the first delivery parameter comprises a piston velocity of the tube, a bore diameter of the hole, and a hole jet velocity;

When a second delivery mode is determined, connecting an injection member with one or more needle members to a tube for needle-wise delivery of the pharmaceutical formulation through the injection head and determining a second delivery parameter of the needle-wise delivery from the preset information, wherein the second delivery parameter comprises the depth of insertion of the needle members, the aperture, the jet velocity and the piston velocity of the tube;

in a selected delivery mode, the pharmaceutical formulation is delivered according to the determined delivery parameters.

In some embodiments of the invention, the preset information comprises at least one of inoculum information, inoculation location information, and pharmaceutical preparation information, wherein the inoculation location information comprises at least one of inoculation site information, delivery depth information, and delivery dispersion information.

In some embodiments of the invention, the dispersion information includes at least one of dispersion volume ratio, dispersion extent, dispersion depth, dispersion center and dispersion edge distribution density.

In some embodiments of the invention, the plurality of holes is a plurality, and the determining the first delivery parameter of the needle-free delivery based on the preset information includes,

And determining the number and arrangement modes of a plurality of holes on the second end of the pipe according to the preset information.

In some embodiments of the invention, the connecting a syringe having one or more needle members to a tube for needle-based delivery of the pharmaceutical formulation through the syringe comprises,

One or more needle members of the injection member are removably docked with corresponding self-closing resilient portions or apertures in the second end of the tube.

In some embodiments of the invention, the determining the second delivery parameter for the needle delivery based on the preset information includes,

And determining the heights, the number and the arrangement modes of the plurality of needle head pieces on the head according to the preset information.

In some embodiments of the invention, the method further comprises mounting a plurality of needle assemblies on the plurality of needle members according to the preset information to adjust the exposed length of the needle members to control the depth of insertion of the plurality of needle members.

The multi-mode fluid delivery device of embodiments of the present invention solves or ameliorates at least one of the following problems or achieves at least one of the following technical effects by configuring the multi-mode fluid delivery device of the present invention, its constituent components, and the associated pharmaceutical and mechanical combination device, and by controlling the flow rates, delivery depths, and dispersion of drug and vaccine jets:

(1) The multi-mode fluid delivery device of the embodiment of the invention is not limited to a single delivery mode, but combines three modes of needleless injection, micro-needle injection and needle injection, comprehensively provides a wider application range, and can meet the delivery requirements of different types of medicaments and vaccines.

(2) The multi-mode fluid delivery device of the embodiments of the present invention can achieve a significant increase in delivery, including without skin break, and can be widely used for drug and vaccine delivery for human and veterinary use.

(3) The multi-mode fluid delivery device provided by the embodiment of the invention has the advantages that the porous needleless delivery is adopted, so that the dispersion volume of the delivery material, especially the medicine and the vaccine in the body is obviously improved, the contact effect of the delivered medicine and vaccine with the tissues in the body is further improved, and the bioavailability of the medicine and the vaccine is obviously improved.

(4) The multi-mode fluid delivery device of the embodiment of the invention realizes the accurate delivery of different drugs and vaccines at different depths in the body according to different drug and vaccine characteristics by accurately controlling the jet flow speed of the drugs and the vaccines and optimizing the pore size and the distribution of the needle-free holes, and particularly realizes the accurate delivery of the delivery object to at least one or a plurality of target positions in the skin, subcutaneous, muscle or human organs.

(5) The multi-mode fluid delivery device provided by the embodiment of the invention realizes different dispersion effects of a delivery object, especially a drug or vaccine, at a delivery position through controlling the aperture and arrangement of the plurality of holes, especially realizes the control of the dispersion volume ratio, the dispersion breadth and the dispersion center at a designated position, and realizes a specific dispersion effect according to different delivery requirements. On the basis of the problems and/or the realization effects, the invention also combines with cat triple vaccine, hepatitis B vaccine, human pneumonia vaccine, GLP-1 polypeptide, especially semaglutinin, to realize the further technical effects as described in the embodiment of the invention.

Example 1

Referring now to fig. 40, 41 and 48, which illustrate one of the structural configurations of the multi-mode fluid delivery device of the embodiment of the present invention, in particular, the second end further 120 has a transition section 122 narrowed distally from the axial direction of the tube 100, the end face 123 of the transition section 122 is configured to be 2.5mm circular in diameter and provided with 3 holes 121 thereon, the 3 holes 121 are annularly arranged at equal intervals around the center of the end face 123, and an angle of 120 ° is formed between the 3 holes and an adjacent line of the center (center) of the center of the end face 123, wherein the apertures of the 3 holes 121 are uniformly set to d and the distances thereof from the center of the end face 123 are uniformly set to l.

Referring now to fig. 42, under the structure of the above-mentioned multi-mode fluid delivery device, the embodiment of the present invention uses the ANSYS workbench Fluent module shown in fig. 42 to build a needleless injection dispersion permeation simulation model, and uses a multiphase flow model to simulate the dispersion situation of the fluid 130 in the body 140 when the power mechanism 200 applies 400N delivery pressure to the fluid 130 contained in the tube 100, where the volume of the fluid 130 to be delivered is 0.2cm3, the viscosity is 1cp, the calculation mode of the needleless injection dispersion permeation simulation model uses a transient, multiphase flow model (Eulerian), a viscosity model uses a K-epsilon Realizable model, and the body 140 model is set as a porous medium, and the initialization method uses a hybrid initialization, and further configures the pore diameter d of the 3 pores 121 and the distance l of the center of the end face 123 of the 3 pores 121 under the above-mentioned structure and simulation parameters, so as to obtain porous needleless delivery fluid dispersion data under the following different configurations:

TABLE 1 porous needleless delivery fluid dispersion data sheet

In combination with table 1 above and as shown in fig. 43-45, the dispersion effect achieved by the multi-mode fluid delivery device of one embodiment of the present invention utilizing a plurality of the holes 121 is shown, the present invention achieves different dispersions of the fluid 130 in the body 140 such that the fluid jets of the fluid 130 through the plurality of holes 121 achieve different dispersion volume ratios, depths of dispersion, and extents of dispersion in the body 10. Wherein, the graph 43 shows a dispersion effect graph at d=0.15 mm, l=0.65 mm, the graph 44 shows a dispersion effect graph at d=0.575 mm, l=0.65 mm, and the graph 45 shows a dispersion effect graph at d=1.00 mm, l=0.65 mm, and meanwhile, when the multi-mode fluid delivery device of the embodiment of the present invention delivers fluid into the body, the dispersion depth and dispersion breadth of the fluid in the body will also cause the fluid to have unused dispersion centers and dispersion edge densities due to different dispersion volume ratios of the fluid in the body, as shown in fig. 43 to 45. In the above embodiments of the invention the injection head and the needle member thereon are removed from the tube, but in other embodiments of the invention a multi-mode fluid delivery device of the invention incorporating the injection head and the needle member is also contemplated having a dispersion effect similar to that described above.

Compared with needleless delivery of a control group, the porous multimode fluid delivery device provided by the embodiment of the invention enables the dispersion volume of the delivery fluid 130 in the simulated body 140 to be 2.09 times to 2.77 times that before delivery, and achieves better dispersion effect on the delivery fluid, in other words, achieves more sufficient contact between the delivery fluid and the in-vivo target site.

Example 2

Referring now to fig. 40, 41 and 48, which illustrate one of the structural configurations of the multi-mode fluid delivery device of the embodiment of the present invention, in particular, the second end 120 has a transition section 122 narrowed distally from the axial direction of the tube 100, an end face 123 of the transition section 122 is configured to be 5mm circular in diameter and provided thereon with a center hole 121″ located at the center (center) of the end face 123 and 3 peripheral holes 121 located at the periphery of the center hole 121', the 3 peripheral holes 121 are arranged annularly at equal intervals around the center of the end face 123, and an angle of 120 ° is formed between adjacent lines of the 3 peripheral holes 121 and the center (center) of the end face 123, wherein the aperture of the center hole 121″ is d ", the aperture of the 3 peripheral holes 121 is uniformly set to d, and d" +.d "is uniformly set to be 1.1mm from the center of the end face 123.

Referring now to fig. 42, under the structure of the multi-mode fluid delivery device described above, the embodiment of the present invention uses the ANSYS workbench Fluent module shown in fig. 42 to construct a needleless injection dispersion and permeation simulation model, and uses a multiphase flow model to simulate the dispersion situation of the fluid 130 in the body 140 when the power mechanism 200 applies 400N delivery pressure to the fluid 130 contained in the tube 100, where the viscosity of the fluid 130 to be delivered is 1cp, the calculation mode of the needleless injection dispersion and permeation simulation model uses a transient, multiphase flow model selects euler model (euler), a viscosity model selects K-epsilon Realizable model, and an in-body 140 model is set as porous media, the initialization method uses hybrid initialization, and further configures the aperture d″ of the central hole 121″ and the aperture d of the 3 peripheral holes 121 under the above structure and simulation parameters, and three groups of simulation experiment fluids are performed to obtain porous needleless delivery fluid dispersion data by using 0.1cm³,0.2cm³ and 0.3cm³, respectively:

TABLE 2 group 1-porous needleless delivery fluid dispersion data sheet

Note that the volume of fluid to be delivered in this set is 0.1cm³.

TABLE 3 group 2-porous needleless delivery fluid dispersion data sheet

Note that the volume of fluid to be delivered in this set is 0.2cm³.

TABLE 4 group 3-porous needleless delivery fluid dispersion data sheet

Note that the volume of fluid to be delivered in this set is 0.3cm³.

In combination with tables 2-4 above and with fig. 46-47, the dispersion achieved by the multi-mode fluid delivery device of one embodiment of the present invention utilizing a plurality of said holes 121 is shown, with the arrangement of the central hole 121 "and 3 peripheral holes 121 such that the fluid jet of fluid 130 through said plurality of holes achieves a significantly enhanced dispersion compared to the needleless delivery of the control group, and in particular, the multi-mode fluid delivery device of an embodiment of the present invention such that the dispersion volume of the delivered fluid 130 in the simulated body 140 is 2.35-3.61 times that before undelivered, in the above embodiments of the present invention, the injection head and needle thereon are removed from the tube, but in other embodiments of the present invention, the multi-mode fluid delivery device of the present invention incorporating the injection head and needle is also expected to have similar dispersion effects as described above. Meanwhile, as is clear from the above table 2 and fig. 46, the multi-mode fluid delivery device of the present invention achieves a dispersion breadth significantly better than that of a single hole at 0.1cm, and achieves a significantly enhanced dispersion effect for the delivery fluid, in other words, achieves a more sufficient contact of the delivery fluid with the in-vivo target site.

Example 3

Referring now to fig. 40, 41 and 48, which illustrate one of the structural configurations of the multi-mode fluid delivery device of the embodiment of the present invention, in particular, the second end 120 has a transition section 122 narrowed distally axially from the tube 100, an end face 123 of the transition section 122 is configured to be 2.5mm circular in diameter and provided with 3 holes 121 thereon, the 3 holes 121 are annularly arranged at equal intervals around the center of the end face 123, and an angle of 120 ° is formed between the 3 holes and an adjacent line of the center (center) of the center of the end face 123, wherein the aperture of the 3 holes 121 is uniformly set to 0.15mm and the distance thereof from the center of the end face 123 is uniformly set to 1.1mm.

Under the above-mentioned structure of the multi-mode fluid delivery device, in one embodiment of the present invention, a delivery fluid with a viscosity of 1cp and a volume of 0.2cm³ is used for testing, so as to obtain a displacement variation curve of the piston 210 of the multi-mode fluid delivery device of the present invention, and accordingly obtain a movement speed of the piston 210 and an outlet jet speed of jet ejected from the plurality of holes 121 as follows:

TABLE 5 piston velocity and jet velocity data sheet

As can be seen from the above table, the multi-mode fluid delivery device of the present invention is configured in one embodiment such that the average velocity of the jets emitted by the plurality of apertures 121 is greater than 135m/s, up to 156m/s. In the above embodiments of the invention the injection head and the needle member thereon are removed from the tube, but in other embodiments of the invention a multi-mode fluid delivery device of the invention incorporating the injection head and the needle member is also contemplated having a dispersion effect similar to that described above.

Example 4

In a specific embodiment of the present invention, the multi-mode fluid delivery device of the present invention is used in combination with a cat triple vaccine, referring to fig. 40, 41 and 48, which illustrate one structural configuration of the multi-mode fluid delivery device of the embodiment of the present invention used in combination with a cat triple vaccine, specifically, the second end 120 has a transition section 122 narrowed axially and distally from the tube 100, wherein the diameter of the tube is 5mm, an end face 123 of the transition section 122 is configured as a circle with a diameter of 2.5mm and provided thereon with 3 holes 121, the 3 holes 121 are arranged annularly at equal intervals around the center of the end face 123, and an angle of 120 ° is formed between adjacent links of the center of the end face 123, wherein the aperture measurement value of the 3 holes 121 is 0.14mm to 0.17mm, and the distance of the 3 holes 121 from the center of the end face 123 is uniformly set to 1.25mm.

In the embodiment of the invention, the cat triple vaccine is a triple inactivated vaccine for preventing cat rhinotracheitis, calicivirus disease and leukopenia. Each part of the cat triple vaccine contains inactivated cat rhinotracheitis virus 605 strain, cat embedded cup virus 255 strain and leukopenia virus Cu-4 strain, and the R.P. value of each component is not lower than 1.0 so as to ensure the immunogenicity and efficacy of the cat triple vaccine. The triple vaccine for cats is only used for vaccinating healthy cats with the age of 8 weeks or more, 1 ml/time of each head can be injected subcutaneously, 1 head of the triple vaccine for healthy cats with the age of 8 weeks or more should be vaccinated after 3-4 weeks after the first vaccination, and 1 head of the triple vaccine for cats with the age of 12 weeks or less should be vaccinated at 12-16 weeks to ensure durable immune protection. The cat triple vaccine should be vaccinated 1-week repeatedly to maintain immunity.

The following is a specific immunoassay test for a multi-mode fluid delivery device of the present invention, wherein, under the structural configuration of the multi-mode fluid delivery device of the present invention described above, a feline vaccine needleless injection immunoassay test was performed according to the following test protocol:

1. Test materials

1.1, Test animals 27 healthy cats are adopted as test animals, wherein the 27 cats are FPV, FHV, FCV antigen negative, and 2/3 of the 3 neutralizing antibody titers are not higher than 1:4 and no triple vaccine immunization history of the cats exists.

1.2 Delivery of vaccine triple inactivated vaccine for feline rhinotracheitis, calicivirus, and leukopenia (trade name: miaosan Duo, lot number: E071201A) by Shuo Teng company.

1.3, Neutralizing antigen for detection, wherein FPV virus liquid, FCV virus liquid and FHV virus liquid with virus content of 200TCID50/0.1ml are selected.

1.4, Cells for detection, CRFK cells or F81 cells were used.

1.5, Test device A multimode fluid delivery device (delivery pressure: 330N, pore size: 0.14 mm-0.17 mm) according to the above embodiment of the invention, a conventional needle 1ml syringe, a 10ml syringe, a medical swab, and an alcohol swab.

1.6, Animal hospital.

2. Test method

2.1, Animal screening, namely collecting a nose swab (capable of being collected in a shallow surface layer), an oral swab and an anal swab for each of the 37 healthy cats, placing the nose swab, the oral swab and the anal swab into a centrifuge tube containing 1ml of PBS, carrying out antigen detection according to the method of 1-3 of the attached notes, collecting 2-3 ml of blood for each healthy cat, separating serum, and carrying out neutralizing antibody detection.

2.2, Grouping animals, namely adapting to the environment 7d after the screened healthy cats enter a test place, gradually transiting cat food, dividing the healthy cats into 3 groups according to sex, age, variety or antibody data of the healthy cats, numbering 7 healthy cats in each group, respectively marking the healthy cats as test groups 1, 2 and 3, and additionally setting 6 healthy cats and non-immunized cat triple vaccine as sentinel animals, marking the healthy cats as test group 4.

2.3, Preparing before immunization, namely circularly playing injection sound for 10-15 min in a test place every day 2-3 days before immunization, and enabling a cat to smell the multi-mode fluid delivery device and the electric shaver. The injection sites of the test cats were shaved 1 day or 2 hours prior to injection, ranging from about 1cm in diameter to 1-2 vaccinators.

2.4 Immunization

Immunization of the aforementioned groups 1,2,3, wherein:

Group 1 was immunized by conventional needle injection using a disposable 1ml syringe with a needle hole diameter of 0.45mm and a dose of 1ml per immunization.

And 2 groups of immunization by using three-hole needleless injection, wherein a needleless injector, a single-hole injection needle head and multi-hole injection are adopted, the aperture of a needle hole is 0.14 mm-0.17 mm, and the immunization dose is 1ml each time.

3 Groups of immunization by needleless multi-hole injection, wherein a needleless injector, a single-hole injection needle head and multi-hole injection are adopted, the aperture of a needle hole is 0.14 mm-0.17 mm, and the immunization dose is 0.45ml each time.

TABLE 6 immunization information Table

Note that "/" indicates no action.

2.5, Sample collection:

On day one and 21 and 35 days after the first day, each cat was collected intravenously according to table 5 above, serum was isolated and stored at-20 ℃. (if the immune response is particularly strong, whole blood is collected 1 to 2 weeks after 35 days).

TABLE 7 sample collection timetable

3. Post immunization results

3.1, Observations on immunization days:

the conventional injection immunization group (1 group) is characterized in that the experimental cats are listless and are not picked up;

the immunized groups (groups 2 and 3) were needleless injected, and the experimental cats were psychoactive.

3.2 Results of measurement of neutralizing antibody titres

The neutralization antibody titer determinations were performed to obtain the following tables 7 and 8, in which the tables of the antibody titer determination data for each group under the above-described test conditions are shown:

TABLE 8 antibody titer determination data Table-1

TABLE 9 antibody titer determination data Table-2

As can be seen from tables 7 and 8 above and fig. 49 to 51, the delivery of the feline triple vaccine using the multi-mode fluid delivery device comprising the plurality of holes 121 in the embodiment of the present invention achieves the following effects compared to the conventional needle delivery:

a. Compared with an immune group with the same dosage as a needle, the immune group with the three holes and the needle-free immune group with the multi-mode fluid delivery device has the advantage that the onset time of the antibodies with the three holes and the needle-free immune group with the multi-mode fluid delivery device is 1 time faster than that of the immune group with the needle;

b. the needleless three-well immunization using the multi-mode fluid delivery device of the present invention was found to produce antibodies 25-fold higher than the antibodies produced by the conventional immunized group with needles at the same immunization dose;

c. The needleless three-well dose halved set using the multi-mode fluid delivery device of the present invention produced 2.4 times higher antibody values than the needleless conventional immunized set.

In the above embodiments of the invention the injection head and the needle member thereon are removed from the tube, but in other embodiments of the invention the multi-mode fluid delivery device of the invention incorporating the injection head and the needle member also contemplates dispersion and immunogenicity effects similar to those described above.

Example 5

In a specific embodiment of the present invention, the multi-mode fluid delivery device of the present invention is used in combination with hepatitis b vaccine, referring to fig. 40, 41 and 48, which show one structural configuration of the multi-mode fluid delivery device of the embodiment of the present invention used in combination with hepatitis b vaccine, specifically, the second end 120 has a transition section 122 narrowed axially distally from the tube 100, wherein the diameter of the tube is 5mm, an end face 123 of the transition section 122 is configured to be 2.5mm circular in diameter and provided with 3 holes 121 thereon, the 3 holes 121 are arranged annularly at equal intervals around the center of the end face 123, and an angle of 120 ° is formed between adjacent links of the 3 holes and the center of the end face 123, wherein the aperture measurement value of the 3 holes 121 is 0.14mm to 0.17mm, and the distance between the 3 holes 121 and the center of the end face 123 is uniformly set to be 1.25mm.

In the embodiment of the invention, the hepatitis B vaccine refers to a hepatitis B recombinant yeast vaccine (hansenula polymorpha) for preventing hepatitis B (a viral liver disease), which is prepared by purifying hepatitis B virus surface antigen (HBsAg) expressed by recombinant hansenula polymorpha and adding an aluminum adjuvant, wherein the active ingredient is the hepatitis B virus surface antigen. The vaccine is suitable for hepatitis B patients, especially for neonates, especially for mothers who are positive for HBsAg and HBeAg, for hepatitis B patients aged 16 years and over 16 years, for medical staff and for blood-contacting laboratory staff. After vaccination, the immune system can be stimulated to produce protective antibodies, so that the human body has the immunity of preventing hepatitis B, and the aim of preventing hepatitis B infection is fulfilled. The conventional immunization site is the upper arm deltoid intramuscular injection. Immunization procedure was 3 needles, vaccinated once at birth (0 month), 1-2 months of age and 6-18 months of age, respectively, and neonates were injected with 1 st needle, 1 dose each time, within 24 hours after birth.

The following is a specific immunoassay test of the multi-mode fluid delivery device of the present invention, wherein the following test protocol was used for the immunization test of hepatitis b vaccine needle-free injection under the structural configuration of the multi-mode fluid delivery device of the present invention:

1. Preparation before test

1.1, Selecting 64 male mice (strain is BALB/c), weighing 17-19 g, feeding for 3-4 weeks, adapting for one week, and collecting blood.

1.2 Test device multimode fluid delivery device according to the above described embodiments of the invention, conventional needle, medical swab and alcohol swab.

2. Test method

2.1, Grouping the 64 mice into 8 groups, including 6 experimental groups and 2 control groups.

TABLE 10 comparative test grouping table

2.2, Blood sampling scheme:

mice were immunized according to the D0/D21 immunization program, and after immunization, D0/D28/D35/D42 were collected and serum was isolated.

At the beginning of the experiment, on the morning of the beginning of the experiment, the back and leg hairs of the mice were shaved with an electric razor and depilatory cream, and all mice were collected with a blood collection amount of 0.2ml per mouse by the retroorbital bleeding method before inoculation.

One needle was inoculated followed by a second needle inoculation at day 21, a second blood collection at day 28, a set of 10 peripheral blood collections, six spleen collections, a third blood collection of all mice at day 35, a fourth blood collection at day 42, 10 peripheral blood collections, six spleen collections.

2.3 Neutralization experiments

The trace method is adopted.

The neutralization endpoint (conversion of serum dilution to log) was calculated by Karber method, i.e. the highest sparsity of serum capable of protecting 50% of cells from infection with 100CCID50 challenge virus was the antibody titer of the serum. Neutralizing antibody titer <1:4 is negative, and 1:4 is positive.

Procedure (fixed virus dilution serum method)

(1) Inactivating serum 56' C for 30 min

(2) Serum is diluted, namely, the inactivated serum is taken and diluted by serum-free cell culture solution on a 96-well microplate, serial multiple dilution is carried out from 1:4, the content of each well is tentatively set to 50 mu L (1:4, 1:28, 1:56, 1:128 and 1:256), and each dilution is 2-4 wells.

(3) Neutralization 50. Mu.L of diluted 200TCID50 virus solution is added to each well, and the mixture is placed in a COg incubator at 37 ℃ for neutralization for 2 hours.

(4) Adding cell suspension, namely neutralizing serum and viruses for 2 hours, taking out the cell plate, adding 0.1 mL/hole cell suspension (preferably, 100-150 ten thousand cells per milliliter are generally grown in 24 hours) into each hole, and culturing in a CO2 incubator for 72 hours for judgment.

2.4 Control experiments

(1) And (3) respectively setting 2-4 holes for negative and positive serum control. The titer of the negative and positive control antibodies should be established.

(2) Virus regression test, namely diluting 200TCID50 virus liquid by 0.1, 1, 10 and 100TCID50, wherein each dilution is 2-4 holes, 50 mu L of each hole, and 50 mu L of cell suspension is added. 0.1TCID50 is not diseased, 100TCID50 is fully diseased, otherwise the experiment is not true.

(3) Cell contrast, namely setting up 2-4-hole normal cell contrast without virus and serum, wherein the contrast cells should keep good morphology and characteristics

2.5, Result determination and calculation

When all of the viral regression test, positive, negative, and cell control are established, the determination can be made. And judging negative when 100% CPE appears in the serum hole to be detected, and judging positive when more than 50% of cells appear as protectors, and calculating the result by using a Karber method.

3. Cell level detection

The spleen of the mouse is collected to measure the content of various T, B cells in the mouse.

3.1, Detection of molecular markers on the surface of T lymphocytes:

Flow cytometry detects T lymphocyte surface molecular markers. The cryopreserved mouse spleen cells were thawed by placing them in a water bath at 37℃to prepare a single cell suspension (1X 107 cells/ml). 0.1ml of the mixture was introduced into a falcon tube, CD3-FITC Ab, CD4-PE Ab, CD8-PE Ab were added, the mixture was placed in a room temperature shadow for 30min, washed 2 times with PBS, and mixed with 0.5ml of PBS. The positive expression rates of two parameters, namely CD3-FITC, CD4-pe and CD8-pe, of T lymphocytes are analyzed by using CELLQuest functional software, and the CD4/CD8 ratio is calculated.

3.2 Enzyme-linked immunosorbent assay:

After blood collection, the supernatant was collected from the ELISPOT plate and stored at-80 ℃ for detection by enzyme-linked immunosorbent assay (ELISA) for 24 hours. Protein expression levels were measured at 450nm using a Biotek ELISA tester, the absorbance value of each cytokine or chemokine was divided by the absorbance value of the pre-inoculation sample as a baseline control to obtain fold changes in cytokines and chemokines, and T cells specific for hepatitis B surface antigens IFN-gamma, IL-2 and IL-4 were generated by ELISPOT analysis, and cellular immune responses were assessed.

3.2.1, Kit content:

PVDF 96-well plate, room temperature storage, 0.1ml capture antibody, 4 ℃ storage, 0.1ml biotin-labeled detection antibody, 4 ℃ storage, 15ul avidin alkaline phosphatase, 4 ℃ storage, 0.25g bovine serum albumin, 4 ℃ storage, 0.25g skim milk, 4 ℃ storage, 11ml substrate buffer, 4 ℃ storage, 11ml concentrated PBS (10X), room temperature storage, 11ml concentrated wash (200X), room temperature storage.

3.2.2 Preparation of reagents:

(1) 10ml of phosphate buffered saline (PBS, 10X) was diluted with 90ml of distilled water;

(2) 0.22g of skim milk was dissolved in 11ml of diluted PBS to a final concentration of 2%;

(3) 0.22gBSA was dissolved in 22ml diluted PBS to a final concentration of 1%

(4) 10Ml of concentrated washing solution (200X) was diluted with 1990ml of distilled water;

(5) 10ul avidin alkaline phosphatase diluted with 10ml PBS-1%, BSA

(6) 7Ml of alcohol was diluted with 3ml of distilled water to a final concentration of 70%.

3.2.2, Stimulation method:

indirect method cells are stimulated in a 24-well plate or flask and then placed in the coated wells.

PBMC (e.g., RPMI 1640 plus 2mm glutamate and 10% heat inactivated calf serum) containing 1ng/ml PMA and 500ng/ml Lonocamycin (Sigma, saint Louis, MO) were diluted in culture broth. Add 2.104 to 5.104 cells to antibody coated PVDF wells and incubate in incubator for 10-15 hours. Other stimulator incubation times may be varied and are optimally selected based on the amount of cytokine-producing cells.

3.2.4, Eli-spot procedure:

(1) PVDF well plates were incubated with 100ul 70% alcohol for 10 minutes at room temperature.

(2) Pouring out alcohol, and washing with 100ul PBS for 3 times.

(3) 100Ul of capture antibody was added to 10ml PBS, mixed, 100ul per well, covered with plate cover, and 4C overnight.

(4) Pouring out the liquid, and washing once by 100ulPBS a.

(5) 100Ul of 2% skim milk PBS (see reagent preparation) was added to each well, covered with plate cover and incubated for 2 hours at room temperature.

(6) Tapping on the side of the water tank and the absorbent paper, and pouring out the liquid.

(7) Wash three times with 100ul PBS for three minutes each.

(8) 100Ul of cell suspension (containing the appropriate amount of cells and corresponding concentration of stimulant) was added to each well. Cells may be pre-stimulated in vitro (indirect Eli-spot). The plates were covered with standard 96-well plastic plates and incubated in a 37℃CCO2 incubator for a period of time (15-20 hours). During which the orifice plate is not shaken or moved.

(9) Tapping on the side of the water tank and the absorbent paper, and pouring out the liquid.

(10) 100Ul of wash buffer was added to each well and incubated at 4℃for 10 min.

(11) Disrupting the cells with pre-chilled ice water.

(12) The wells were washed eight times with 100ul of wash PBST buffer for four minutes each.

(13) 100Ul of detection antibody was diluted in 10ml PBS-1% BSA, in one plate. 100ul of this liquid was added to each well, covered with a plate cover and incubated at 37℃for 2 hours.

(14) Pouring out the liquid, and washing with 100ul of washing buffer for 5 times.

(15) 10Ul of avidin alkaline phosphatase was diluted per plate with 10ml of PBS1% BSA. 100ul of this liquid was added to each well, covered with a plate cover and incubated at 37℃for 1 hour.

4. Statistical analysis

Statistical analysis the differences between the groups were statistically significant using one-way anova and t-test (GRAPHPAD PRISM 8.0.0) analysis, and the data were expressed as mean ± Standard Deviation (SD). p-value <0.05 was considered statistically significant.

5. Final result

The multimodal fluid delivery device of the present invention is configured such that the average antibody titer of the hepatitis B vaccine 14 days after the second dose is inoculated is more than 1.1 times the average antibody titer of the needle injection;

the multimodal fluid delivery device of the present invention is configured such that the average antibody titer of the hepatitis B vaccine 42 days after the second dose is inoculated is greater than 1.5 times the average antibody titer of the needle injection;

The multimodal fluid delivery device of the present invention is configured such that the hepatitis B vaccine has a T lymphocyte positive expression rate greater than 10% after 42 days of vaccination with the second dose.

In the above embodiments of the invention the injection head and the needle member thereon are removed from the tube, but in other embodiments of the invention the multi-mode fluid delivery device of the invention incorporating the injection head and the needle member also contemplates dispersion effects and immunogenic effects similar to those described above.

Example 6

In a specific embodiment of the present invention, the multi-mode fluid delivery device of the present invention is used in combination with GLP-1 based polypeptides, in particular with a cable Ma Lutai, referring to fig. 40, 41 and 48, which show one structural configuration of the multi-mode fluid delivery device of the embodiment of the present invention used in combination with a cable Ma Lutai, in particular, the second end 120 has a transition section 122 narrowing axially distally from the tube 100, wherein the diameter of the tube is 5mm, the end face 123 of the transition section 122 is configured to be 2.5mm circular in diameter and provided with 3 holes 121 thereon, the 3 holes 121 are arranged annularly at equal intervals around the center of the end face 123, the adjacent line of the center of the 3 holes and the center of the end face 123 form an angle of 120 °, wherein the aperture measurement value of the 3 holes 121 is 0.14mm to 0.17mm, and the distance of the 3 holes 121 from the center of the end face 123 is uniformly set to 1.25mm.

In the embodiment of the invention, the semaglutin (Simeigelutai), also called as Soxhlet Ma Lutai, is a second-generation glucagon-like peptide-1 (GLP-1) analogue, has a molecular formula of C₁₈₇H₂₉₁N₄₅O₅₉ (the molecular weight is 4113.58 Da), has excellent hypoglycemic and weight-reducing effects on diabetics, is obviously superior to sitagliptin, insulin glargine U100 or slow-release exenatide, and is also superior to the litalunin which is an identical medicament in weight reduction, particularly in patients with BMI of more than or equal to 30. The semaglutin can be administered orally or subcutaneously, for example, in an oral dosage form of 7mg/14mg once a day or in a subcutaneous dosage form of 0.5mg/1.0mg once a week. The semaglutin has good curative effect in diabetes treatment, and has obvious advantages in aspects of weight reduction and cardiovascular protection.

The following is a specific semaglutin rat test of the multi-mode fluid delivery device of the present invention, wherein the semaglutin rat test was performed using semaglutin of the following structure in the structural configuration of the multi-mode fluid delivery device of the present invention as described above according to the following test protocol:

1. Test materials

1.1, Test animals selection

Healthy male Wistar rats, age 6-8 weeks, weight 200-250 grams.

1.2, Test group the rats were randomly divided into four groups of 10 rats each.

1.3, Delivering a medicament, semaglutin;

1.4, test equipment, a multimode fluid delivery device (delivery pressure: 250N, aperture: 0.14 mm-0.17 mm) according to the above embodiment of the invention, a conventional needled syringe, a medical cotton swab, and alcohol cotton.

2. Test procedure

2.1 Administration of drugs

In the needleless delivery set, administration is performed using a multi-mode fluid delivery device according to set parameters, and in the needleless delivery set, administration is performed using a conventional injection method, wherein:

group 1, 1x dose with needle, 14 days per day;

group 2, needleless 1x dose, 14 days per day;

group 3, 10x dose with needle, 2 weeks per week;

group 4, needleless 10x dose, weekly for 2 weeks;

2.2 data collection

Daily recordings of rat body weight changes, monitoring of blood glucose and insulin levels.

3. Evaluation of results

Group 1 and group 2 comparisons the total proportion of weight loss for group 2 (needleless delivery) was 4% greater than for group 1 (needleless delivery) at the same dosing dose (1 x) and frequency (daily). In addition, the effect duration of group 2 is long, and the rebound time is delayed from group 1.

Comparison of group 3 and 4 the total proportion of weight loss for group 4 (needleless delivery) was 5.5% greater than for group 3 (needleless delivery) at higher doses (10 x) and less frequent (weekly) conditions.

In the above embodiments of the invention the injection head and the needle member thereon are removed from the tube, but in other embodiments of the invention the multi-mode fluid delivery device of the invention incorporating the injection head and the needle member also contemplates dispersion effects and immunogenic effects similar to those described above.

Example 7

In a specific embodiment of the present invention, the multi-mode fluid delivery device of the present invention is used in combination with a polypeptide seed vaccine, referring to fig. 40, 41 and 48, which illustrate one structural configuration of the multi-mode fluid delivery device of the embodiment of the present invention used in combination with a polypeptide seed vaccine, specifically, the second end 120 has a transition section 122 narrowed from the tube 100 axially to the distal end, wherein the diameter of the tube is 5mm, the end surface of the transition section 122 is configured as a circle with a diameter of 2.5mm and provided with 3 holes 121 thereon, the 3 holes 121 are arranged in a circular shape at equal intervals around the center of the end surface 123, the 3 holes form an angle of 120 ° with the adjacent line of the center of the end surface 123, wherein the measured value of the aperture of the 3 holes 121 is 0.14mm to 0.17mm, and the distance of the 3 holes 121 from the center of the end surface 123 is uniformly set to 1.25mm.

In the embodiment of the invention, the polypeptide tumor vaccine is a novel vaccine, which is essentially an immunogen for inducing effector cell immune response in vivo, the tumor polypeptide vaccine is an antigen polypeptide eluted from the surface of tumor cells or a related polypeptide which is obtained from the tumor cells and can improve body anti-tumor humoral immunity and cellular immunity after immunizing a body, and currently, the widely studied tumor polypeptide vaccine comprises a vaccine for targeting a folic acid receptor (FR) or developing against a HER2 target.

The following is a specific polypeptide tumor vaccine rat immunization test of the multi-mode fluid delivery device of the present invention, wherein the polypeptide tumor vaccine rat immunization test was performed according to the following test protocol under the structural configuration of the multi-mode fluid delivery device of the present invention described above:

1. Test materials

1.1 Test animals 60 healthy male C57BL/6 mice were selected, aged 6-8 weeks, weighing 18-22G, and were divided into six experimental groups G1, G2, G3, G4, G5 and G6 (10 per group) by the random digital method.

1.2, Test equipment, neoantigen, positive control polypeptide and the multimode fluid delivery device according to the embodiment of the invention, wherein the aperture is 0.14-0.17 mm, and the delivery pressure is 160N.

2. Immunoassay test

2.1, Experimental arrangement:

3 or 4 rounds of immunization experiments were performed in groups according to the following table 6:

TABLE 11 information table of immunization test of polypeptide seed tumor vaccine rats

3. Effect detection

3.1, Detection method, after the immunization is finished, taking the spleen cells of the mice as detection results of 4 rounds of ELISPOT detection

3.2, Detection result:

a. Positive signals of the new antigen group were detected by Elispot experiments after three/four rounds of immunization of the mice, but the signals were weaker.

B. there was no statistical difference in the number of flat spots between the needleless injection group and the needleless injection group.

C. The number of spots in each experimental group after the fourth round is less than that of the third round of immunization. The needleless neoantigen group was 10% less than the needleless neoantigen group and 20% less than the positive polypeptide group for the reduced proportion, thus demonstrating that the needleless neoantigen polypeptide vaccine was longer effective than the other two groups.

In the above embodiments of the invention the injection head and the needle member thereon are removed from the tube, but in other embodiments of the invention the multi-mode fluid delivery device of the invention incorporating the injection head and the needle member also contemplates dispersion effects and immunogenic effects similar to those described above.

The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (86)

1. A multi-mode fluid delivery device, comprising:

a tube for containing a fluid, the tube having a first end and a second end, the second end having a self-closing resilient portion disposed therein or an aperture for distributing the fluid within the tube;

An injection head detachably connected to the tube, the injection head comprising one or more needle members configured to removably interface with a self-closing spring in the second end or a hole for fluid within a dispensing tube, and

A power mechanism including a piston disposed in the first end of the tube capable of pushing the fluid or operatively connected to the piston to apply delivery pressure to the piston pushing the fluid.

2. The multi-mode fluid delivery device of claim 1, wherein the power mechanism is any one of compressed gas drive, spring drive, electromagnetic drive, or a combination thereof;

the pushing speed of the piston of the multi-mode fluid delivery device is 0.05-0.50 m/s, preferably 0.09-0.25 m/s, and even more preferably 0.14-0.25 m/s;

the multi-mode fluid delivery device is configured such that the outlet jet velocity of the fluid as it is pushed by the piston out of the bore in the second end or the one or more needle members is 10m/s or more, preferably 50m/s or more, further preferably 100m/s or more, still further preferably 150m/s or more.

3. The multi-mode fluid delivery device of claim 1 or 2, wherein at least one of the one or more needle members is substantially inserted into a human or animal body;

Preferably, at least one of the one or more needle members has a bore diameter in the range of 0.06mm to 1.50mm, more preferably in the range of 0.11mm to 1.00mm, still more preferably in the range of 0.11mm to 0.50 mm;

Preferably, at least one of the self-closing resilient portion or the aperture for the fluid in the dispensing tube has a diameter in the range of 0.06mm to 1.50mm, more preferably in the range of 0.11mm to 1.00mm, still more preferably in the range of 0.11mm to 0.50 mm.

4. A multi-mode fluid delivery device according to claim 1 or 2, wherein the total fluid delivery area of the plurality of needle members or the plurality of apertures for distributing the fluid within the tube is 0.009mm² or more, preferably 0.020mm² or more, more preferably 0.053mm² or more preferably 0.28mm² or more, and the single aperture area of the needle members or apertures is 0.0028-0.035 mm², preferably 0.0028-0.020mm², more preferably 0.0028-0.009 mm².

5. The multi-mode fluid delivery device of claim 1 or2, wherein the one or more needle members have different adjustable skin insertion depths;

preferably, at least one of the one or more needle members has an insertion depth that does not substantially insert but that is in intimate contact with human or animal skin;

preferably, at least one of the one or more needle members has an insertion depth that is substantially inserted into the inner layer of the human or animal skin;

preferably, at least one of the one or more needle members has an insertion depth that is substantially into the subcutaneous layer of the human or animal body;

Preferably, at least one of the one or more needle members has an insertion depth that is substantially inserted into a muscle layer of a human or animal;

Preferably, at least one of the one or more needle members has an insertion depth of substantial insertion into an organ in a human or animal body;

preferably, at least one of the one or more needle members has an adjustable depth of insertion.

6. The multi-mode fluid delivery device of claim 1 or 2, wherein,

The multi-mode fluid delivery device is configured such that the fluid has a larger volume of dispersion in the body than the undelivered volume, preferably a volume of dispersion in the body that is 1.50 times or more, preferably 1.80 times or more, further preferably 2.40 times or more, more preferably 3.00 times or more, still further preferably 3.60 times or more the undelivered volume.

7. The multi-mode fluid delivery device of claim 1 or 2, wherein the plurality of needle members comprises a first needle member;

Preferably, the first needle member has a first skin insertion depth in one of a dermis layer, an epidermis layer, a subcutaneous layer, a muscle and a human organ;

Preferably, the first needle member has a first needle aperture sized such that the fluid jet passing through the first needle member is dispersed in at least one of the dermis, epidermis, subcutaneous, muscle and human organ;

preferably, the first needle member has a first outlet jet velocity configured such that the fluid jet passing through the first needle member is dispersed in at least one of the dermis layer, epidermis layer, subcutaneous, muscle and human organ.

8. The multi-mode fluid delivery device of claim 1 or 2, wherein the plurality of needle members comprises a first needle member and a second needle member;

Preferably, the first needle member has a first skin insertion depth in one of a dermis layer, an epidermis layer, a subcutaneous layer, a muscle and a human organ, and the second needle member has a second skin insertion depth in the other of the dermis layer, the epidermis layer, the subcutaneous layer, the muscle and the human organ;

Preferably, the first needle member has a first needle aperture sized such that the fluid jet passing through the first needle member is dispersed in at least one of the dermis, epidermis, subcutaneous, muscle and human organ; the second needle member having a second needle aperture sized such that a fluid jet passing through the second needle member is dispersed in at least one other of the dermis, epidermis, subcutaneous, muscle and human organ;

preferably, the first needle member has a first outlet jet velocity configured to cause the fluid jet passing through the first needle member to disperse in at least one of the dermis, epidermis, subcutaneous, muscle and human organ, and the second needle member has a second outlet jet velocity configured to cause the fluid jet passing through the second needle member to disperse in at least one other of the dermis, epidermis, subcutaneous, muscle and human organ.

9. The multi-mode fluid delivery device of claim 8, wherein the plurality of needle members further comprises a third needle member;

preferably, the third needle member has a third skin insertion depth in one of the dermis layer, epidermis layer, subcutaneous, muscle and human organ;

Preferably, the third needle member has a third needle aperture sized such that the fluid jet passing through the third needle member is dispersed in at least one of the dermis layer, epidermis layer, subcutaneous layer, dermis layer, epidermis layer, or subcutaneous layer of muscle and human organ;

Preferably, the third needle has a third outlet jet velocity configured such that the fluid jet passing through the third needle is dispersed in at least one more of the dermis, epidermis, subcutaneous, muscle and human organ.

10. The multi-mode fluid delivery device of claim 1 or 2, wherein the plurality of needle members are aligned in a straight line;

preferably, the plurality of needle members are arranged in a straight line along the diameter or the center line of the injection head, and preferably, one of the plurality of needle members arranged in a straight line along the diameter or the center line of the injection head is positioned at the center or the center of the injection head;

Preferably, the plurality of needle members arranged in a straight line are arranged at equal intervals;

preferably, the plurality of needle members aligned in a straight line are mirror-symmetrical with respect to a diameter or midline of the injection head;

preferably, the needle members have a plurality of sets, each set of needle members being arranged along a straight line, preferably each set of needle members being arranged along a diameter or a midline of the injection head;

the plurality of needle members are arranged in an array, preferably the plurality of needle members in an array are mirror images of each other with respect to first and second mutually perpendicular diameters or midlines of the injection head.

11. The multi-mode fluid delivery device of claim 10, wherein,

The skin insertion depth of the needle piece located at the center or center of the injection head is different from the skin insertion depth of the other needle pieces of the plurality of needle pieces;

Preferably, the skin insertion depth of at least one of the plurality of sets of needle members is different from the skin insertion depth of the other sets of needle members;

Preferably, the needle aperture of the needle member located at the center or centre of the injection head is different from the needle apertures of the other needle members of the plurality of needle members;

preferably, the needle apertures of at least one of the plurality of sets of needle elements are different from the needle apertures of the other sets of needle elements;

Preferably, the outlet jet velocity of the needle member located at the centre or centre of the injection head is different from the outlet jet velocity of the other needle members of the plurality of needle members;

Preferably, the outlet jet velocity of at least one of the plurality of sets of needle members is different from the outlet jet velocities of the other sets of needle members.

12. The multi-mode fluid delivery device of claim 1 or 2, wherein the plurality of needle members are arranged in an annular pattern;

preferably, the plurality of needle head pieces are annularly arranged with the center of the injection head or the center as the center of the circle;

the needle members have a plurality of sets, each set being arranged in an annular pattern, preferably the plurality of sets being arranged in an annular pattern coaxially with one another.

13. The multi-mode fluid delivery device of claim 12, wherein,

At least one of the plurality of needle members in the annular array has a skin insertion depth that is different from the other needle members;

preferably, the skin insertion depth of at least one of the plurality of sets of needle members is different from the skin insertion depth of the other sets of needle members;

preferably, the skin insertion depths of the plurality of sets of needle assemblies arranged coaxially and annularly with each other are radially decreasing or increasing;

Preferably, at least one of the plurality of needle members in the annular array has a needle aperture different from the other needle members;

preferably, the needle apertures of at least one of the plurality of sets of needle elements are different from the needle apertures of the other sets of needle elements;

preferably, the needle apertures of said plurality of sets of needle assemblies arranged coaxially and annularly with each other decrease or increase radially;

Preferably, at least one of the plurality of needle members in the annular array has an outlet jet velocity different from the other needle members;

Preferably, the outlet jet velocity of at least one of the plurality of sets of needle members is different from the outlet jet velocities of the other sets of needle members;

preferably, the outlet jet velocities of the plurality of sets of needle assemblies arranged coaxially and annularly with each other are radially decreasing or increasing.

14. The multi-mode fluid delivery device of claim 1 or 2, wherein the plurality of needle members comprises a central needle member located at a center or center of the injection head and a plurality of peripheral needle members located at a periphery of the central needle member;

preferably, said plurality of peripheral needle members are arranged in an annular pattern, preferably said plurality of peripheral needle members are arranged in a coaxial annular pattern around said central needle member;

The peripheral needle members have a plurality of sets, each set of peripheral needle members being arranged in an annular pattern, preferably the plurality of sets of peripheral needle members being arranged in a coaxial annular pattern about the central needle member.

15. The multi-mode fluid delivery device of claim 14, wherein the fluid delivery device comprises,

The skin insertion depth of the central needle member is different from the skin insertion depth of the plurality of peripheral needle members;

preferably, the skin insertion depth of at least one set of peripheral needle members of said plurality of sets of peripheral needle members is different from the skin insertion depth of the other peripheral sets of needle members;

Preferably, the skin insertion depth of said plurality of sets of needle members and said central needle member coaxially and annularly arranged with respect to each other decreases or increases radially;

preferably, the needle apertures of the central needle member are different from the needle apertures of the plurality of peripheral needle members;

Preferably, the needle apertures of at least one set of peripheral needle members of said plurality of sets of peripheral needle members are different from the needle apertures of the other peripheral sets of needle members;

Preferably, the needle apertures of said plurality of sets of needle members and said central needle member, coaxially and annularly arranged with respect to each other, are radially increasing or decreasing;

Preferably, the outlet jet velocity of the central needle member is different from the outlet jet velocities of the plurality of peripheral needle members;

preferably, the outlet jet velocity of at least one set of peripheral needle members of said plurality of sets of peripheral needle members is different from the outlet jet velocities of the other peripheral sets of needle members;

preferably, the outlet jet velocities of the plurality of sets of needle members and the central needle member, coaxially and annularly arranged with respect to each other, decrease or increase radially.

16. The multi-mode fluid delivery device of any one of claims 1 to 15, wherein the injection head comprises a support for supporting the needle;

preferably, the needle member further comprises a first needle portion on a side of the support portion facing away from the tube;

preferably, the needle member includes a fixing pad on a side of the supporting portion facing the tube, the fixing pad for fixing the needle member;

Preferably, the needle member includes a second needle portion on a side of the support portion facing the tube;

alternatively, the needle member does not extend from a side of the support portion facing away from the tube, such that a side of the support portion facing away from the needle cannula forms a needleless micropore.

17. The multi-mode fluid delivery device of claim 16, wherein the needle member comprises an interventional soft needle removably connected to the bore of the tube.

18. The multi-mode fluid delivery device of claim 16, further comprising a needle set comprising a needle sleeve for removably surrounding a first needle portion of the needle set.

19. The multi-mode fluid delivery device of claim 18, wherein a height of a needle sleeve of the needle set is greater than or equal to the first needle portion of the needle piece, thereby completely surrounding the first needle portion;

Optionally, the needle sleeve of the needle set has a height less than the first needle portion of the needle member, thereby partially surrounding the first needle portion such that the first needle portion protrudes from the needle sleeve front end to form an insert.

20. The multi-mode fluid delivery device of claim 19, wherein the needle set comprises a first needle set having a needle sleeve with a height greater than the first needle portion of the needle set to completely surround the first needle portion to protect the first needle portion.

21. The multi-mode fluid delivery device of claim 19, wherein the plurality of needle sets, preferably the plurality of needle sets comprises a first needle set and a second needle set,

The first needle set is configured such that it surrounds the first needle portion with one of a partially surrounded, insertion site located in the dermis layer, in the epidermis layer, subcutaneously, in the muscle, or in a human organ;

The second needle set is configured such that it surrounds the first needle portion with the other one of partially surrounded, inserted at the dermis layer, at the epidermis layer, subcutaneously, in muscle or in an organ of the human body.

22. The multi-mode fluid delivery device of claim 18, wherein the plurality of needle assemblies is a plurality, preferably the plurality of needle assemblies includes a first needle assembly, a second needle assembly, a third needle assembly, a fourth needle assembly, a fifth needle assembly, and a sixth needle assembly;

The first needle set is configured such that it surrounds the first needle portion completely surrounded;

the second needle set is configured such that it surrounds the insertion site of the first needle portion in the dermis layer;

The third needle set is configured such that it surrounds the insertion site of the first needle portion in the epidermis layer;

The fourth needle set is configured such that its insertion portion surrounding the first needle portion is subcutaneously;

the fifth needle set is configured such that its insertion portion surrounding the first needle portion is located in the muscle;

the sixth needle set is configured such that an insertion portion thereof surrounding the first needle portion is located in a human organ.

23. The multi-mode fluid delivery device of claim 16, wherein the injection head further comprises a hub portion sleeved on the needle member and a rotating member operatively connected to the needle member or hub portion, the rotating member configured to adjust an axial position of the needle member and hub portion by rotation to adjust an exposed length of the needle member relative to the hub portion.

24. The delivery device of claim 23, wherein the axial positions of the needle member and the hub portion are configured to be adjustable between a plurality of positions such that the exposed length of the needle member is adjustable between a plurality of positions, preferably the exposed length of the needle member is adjustable between a plurality of positions retracted from the hub portion, flush with the hub portion, in the dermis layer, in the epidermis layer, subcutaneously, in the muscle, in a human organ;

preferably, the axial positions of the needle member and the needle hub are configured to be continuously adjustable such that the exposed length of the needle member is continuously adjustable.

25. The multi-mode fluid delivery device of any one of claims 1 to 24, wherein the injection head comprises a connection for detachably connecting the injection head to the tube;

Preferably, the connecting part is a threaded connecting part;

Optionally, the connecting part is a clamping part;

optionally, the connection portion is an adhesive portion.

26. The multi-mode fluid device of any one of claims 1 to 24, further comprising a locking member for locking the injection head to the tube, the locking member comprising a connection portion for detachably connecting the locking member to the tube;

Preferably, the connecting part is a threaded connecting part;

Optionally, the connecting part is a clamping part;

optionally, the connection portion is an adhesive portion.

27. A combination feline triple vaccine and drug product comprising a multimode fluid delivery device and a feline triple vaccine, wherein the multimode fluid delivery device is a multimode fluid delivery device according to any one of claims 1 to 26.

28. The pharmaceutical apparatus of claim 27, wherein the second end is provided with three holes, the three holes are annularly arranged at equal intervals around the center of the second end, the aperture of the three holes is 0.10 mm-0.17 mm, and the distance between the three holes and the center of the circle is 1.25mm ± 20%.

29. The pharmaceutical-mechanical combination of claim 27, wherein the push rate of the piston of the multi-mode fluid delivery device is 0.12m/s ± 20%.

30. The pharmaceutical-mechanical combination of claim 27, wherein the multi-mode fluid delivery device is configured such that the exit jet velocity of the cat triple vaccine when pushed by the piston out of the bore in the second end is 150.00m/s ± 20%.

31. The pharmaceutical mechanical combination of claim 27, wherein the multi-mode fluid delivery device is configured such that the dispersion volume of the feline triple vaccine in vivo is greater than 1.5 times the undelivered volume of the feline triple vaccine.

32. The pharmaceutical-mechanical combination of claim 27, wherein the multi-mode fluid delivery device is configured such that the average antibody titer of the cat triple vaccine 14 days after the second dose is 1.2-fold or more, preferably 2.0-fold or more, still preferably 4.8-fold or more of the average antibody titer of the needle injection.

33. The pharmaceutical-mechanical combination of claim 27, wherein the multi-mode fluid delivery device is configured such that the average antibody titer of the feline triple vaccine 30 days after the second dose is greater than 1.2 times, preferably greater than 2.0 times, still preferably greater than 3.7 times the average antibody titer of the needle injection.

34. The pharmaceutical mechanical combination of claim 27, wherein the multi-mode fluid delivery device is configured such that the average antibody titer of the feline triple vaccine 60 days after the injection of the second dose of 60% vaccine dose is 1.1 times or more, preferably 1.5 times or more, still preferably 2.0 times or more the average antibody titer produced by the needle injection of the 100% vaccine dose.

35. A combination hepatitis b vaccine and pharmaceutical apparatus comprising a multi-mode fluid delivery device and a hepatitis b vaccine, wherein the multi-mode fluid delivery device is a multi-mode fluid delivery device according to any one of claims 1 to 26.

36. The pharmaceutical apparatus of claim 35, wherein the second end is provided with three holes, the three holes are annularly arranged at equal intervals around the center of the second end, the aperture of the three holes is 0.10 mm-0.17 mm, and the distance between the three holes and the center of the circle is 1.25mm ± 20%.

37. The pharmaceutical-mechanical combination of claim 35, wherein the push rate of the piston of the multi-mode fluid delivery device is 0.12m/s ± 20%.

38. The pharmaceutical-mechanical combination of claim 35, wherein the multi-mode fluid delivery device is configured such that the exit jet velocity of the hepatitis b vaccine as it is pushed by the piston out of the bore in the second end is 150.00m/s ± 20%.

39. The pharmaceutical mechanical combination of claim 35, wherein the multi-mode fluid delivery device is configured such that the dispersion volume of the hepatitis b vaccine in vivo is greater than 1.5 times the undelivered volume of the hepatitis b vaccine.

40. The pharmaceutical mechanical combination of claim 35, wherein the multi-mode fluid delivery device is configured such that the average antibody titer of the hepatitis b vaccine after 42 days of vaccination is 1.1 times or more, preferably 1.5 times or more, still preferably 2.0 times or more the average antibody titer of the needle injection.

41. The pharmaceutical-mechanical combination of claim 35, wherein the multi-mode fluid delivery device is configured such that the positive expression rate of T lymphocytes is 10% higher, preferably 20% higher, more preferably 50% higher than that of the needled injection 42 days after the second dose of hepatitis b vaccine.

42. A pneumonitis vaccine pharmaceutical combination product for humans, comprising a multi-mode fluid delivery device and a pneumonitis vaccine for humans, wherein the multi-mode fluid delivery device is a multi-mode fluid delivery device according to any one of claims 1 to 26.

43. The combination of claim 42, wherein the second end is provided with three holes, the three holes are annularly arranged at equal intervals around the center of the second end, the aperture of the three holes is 0.10 mm-0.17 mm, and the distance between the three holes and the center of the circle is 1.25mm +/-20%.

44. The pharmaceutical-mechanical combination of claim 42, wherein the push rate of the piston of the multi-mode fluid delivery device is 0.14m/s ± 20%.

45. The pharmaceutical mechanical combination of claim 42, wherein the multi-mode fluid delivery device is configured such that the exit jet velocity of the human pneumonitis vaccine as pushed by the piston out of the aperture in the second end is 160.00m/s ± 20%.

46. The pharmaceutical mechanical combination of claim 42, wherein the multi-mode fluid delivery device is configured such that the dispersion volume of the human pneumonic vaccine in the body is greater than 1.5 times the undelivered volume of the human pneumonic vaccine.

47. The pharmaceutical mechanical combination according to claim 42, wherein the multi-mode fluid delivery device is configured such that the average antibody titer after 42 days of vaccination of the pneumonia vaccine is 1.1 times or more, preferably 1.5 times or more, still preferably 2.0 times or more the average antibody titer of the needle injection.

48. A GLP-1 class polypeptide pharmaceutical device combination comprising a multi-mode fluid delivery device and a GLP-1 class polypeptide, wherein the multi-mode fluid delivery device is a multi-mode fluid delivery device according to any one of claims 1 to 26.

49. The combination of claim 48, wherein the second end is provided with three holes, the three holes are annularly arranged at equal intervals around the center of the second end, the aperture of the three holes is 0.10 mm-0.17 mm, and the distance between the three holes and the center of the circle is 1.25mm +/-20%.

50. The pharmaceutical mechanical combination of claim 48, wherein the multi-mode fluid delivery device is configured such that the dispersion volume of the GLP-1 class polypeptide in vivo is greater than 1.5 times the undelivered volume of the GLP-1 class polypeptide.

51. The pharmaceutical-mechanical combination of claim 48, wherein the push rate of the piston of the multi-mode fluid delivery device is 0.16m/s ± 20%;

the multi-mode fluid delivery device is configured such that the outlet jet velocity of the GLP-1 class polypeptide as it is pushed by the plunger out of the bore in the second end is 160.00m/s ± 20%.

52. The pharmaceutical-mechanical combination according to claim 48, wherein the multi-mode fluid delivery device is configured such that the GLP-1 class polypeptide has a weight reducing effect on humans and animals consistent with a needle injection, preferably a weight reducing effect of 2%, more preferably 5%, still more preferably 10% higher than a needle injection.

53. The pharmaceutical-mechanical combination according to claim 48, wherein the multi-mode fluid delivery device is configured such that the GLP-1 class polypeptide is at an end of weight loss in vivo consistent with a needle injection, preferably by more than 2%, further preferably by more than 5%, still further preferably by more than 10%.

54. The pharmaceutical-mechanical combination according to claim 48, wherein the multi-mode fluid delivery device is configured such that the GLP-1 class polypeptide causes a consistent proportion of side effects such as nausea, vomiting, abdominal distension, etc., as compared to a needle injection, preferably by more than 5%, more preferably by more than 10%, still more preferably by more than 20%.

55. A pharmaceutical-mechanical combination comprising a multi-mode fluid delivery device and a pharmaceutical formulation, the multi-mode fluid delivery device being a multi-mode fluid delivery device according to any one of claims 1 to 26.

56. The pharmaceutical combination of claim 55, wherein,

Optionally, the pharmaceutical formulation is a rabies vaccine for humans;

Optionally, the pharmaceutical formulation is a rabies vaccine for animals;

optionally, the pharmaceutical formulation is a meningitis vaccine for humans;

optionally, the pharmaceutical preparation is a hand-foot-and-mouth disease vaccine for animals;

optionally, the pharmaceutical formulation is a human new crown vaccine;

optionally, the pharmaceutical formulation is a human hepatitis a vaccine;

optionally, the pharmaceutical formulation is a human kidney syndrome hemorrhagic fever vaccine;

Optionally, the pharmaceutical formulation is a mumps vaccine for human use;

alternatively, the pharmaceutical formulation is a HPV vaccine for human use;

optionally, the pharmaceutical formulation is a human tumor chemotherapeutic;

optionally, the pharmaceutical formulation is a human tumor nuclear medicine therapeutic drug;

alternatively, the pharmaceutical formulation is a human tumor vaccine, including but not limited to a polypeptide vaccine, an mRNA vaccine, a DNA vaccine;

Optionally, the pharmaceutical formulation is a porcine diarrhea bivalent vaccine;

Optionally, the pharmaceutical formulation is a blue-ear inactivated vaccine;

optionally, the pharmaceutical formulation is a foot-and-mouth vaccine;

optionally, the pharmaceutical formulation is a bovine bivalent vaccine;

Optionally, the pharmaceutical formulation is a papanicolaou vaccine;

Optionally, the pharmaceutical formulation is insulin;

Optionally, the pharmaceutical formulation is a botulinum-type cosmetic drug for medical cosmetology.

57. A tube for a multi-mode fluid delivery device, characterized in that,

The tube has a first end configured to receive a piston for pushing fluid within the tube and a second end having a self-closing spring or a plurality of holes disposed therein for dispensing fluid within the tube.

58. The tube of claim 57, wherein the tube is configured such that fluid jets through the plurality of apertures have different in vivo dispersions;

Preferably, the apertures of the plurality of holes of the tube are configured such that the fluid jets passing through the plurality of holes have different in vivo dispersions.

59. The tube of claim 57, wherein the plurality of holes comprises a first hole;

Preferably, the first aperture has a first aperture size configured such that the fluid jet passing through the first aperture is dispersed in at least one of the dermis, epidermis, subcutaneous, muscle and human organ.

60. The tube of claim 57, wherein the plurality of holes comprises a first hole and a second hole;

Preferably, the first aperture has a first aperture size configured such that the fluid jet passing through the first aperture is dispersed in at least one of the dermis, epidermis, subcutaneous, muscle and human organ, and the second aperture has a second aperture size configured such that the fluid jet passing through the second aperture is dispersed in at least one other of the dermis, epidermis, subcutaneous, muscle and human organ.

61. The tube of claim 57, wherein the plurality of holes are aligned in a straight line;

Preferably, the plurality of holes are arranged in a straight line along the diameter or the center line of the second end, and preferably, one of the plurality of holes arranged in a straight line along the diameter or the center line of the second end is positioned at the center of the second end;

preferably, the plurality of holes arranged in a straight line are arranged at equal intervals;

Preferably, the plurality of holes aligned in a straight line are mirror symmetrical with respect to a diameter or midline of the second end;

preferably, the holes have a plurality of groups, each group of holes being aligned along a straight line, preferably each group of holes being aligned along a diameter or a midline of the second end;

Preferably, said plurality of holes are arranged in an array, said plurality of holes in an array being mirror symmetrical with respect to first and second mutually perpendicular diameters or midlines of said second end, respectively;

preferably, the aperture of the hole located at the center or centre of the second end is different from the aperture of the other holes of the plurality of holes;

preferably, the apertures of at least one of the plurality of sets of apertures are different from the apertures of the other sets of apertures.

62. The tube of claim 57, wherein the plurality of holes are arranged in an annular pattern;

Preferably, the holes are annularly arranged with the center of the second end or the center as the center;

The holes have a plurality of groups, each group of holes being arranged in an annular manner, preferably the plurality of groups of holes being arranged in an annular manner coaxially with each other;

preferably, at least one of the plurality of holes in the annular array has a different pore size than the other holes;

Preferably, the apertures of at least one group of apertures of the plurality of groups of apertures are different from the apertures of the other groups of apertures;

preferably, the apertures of the plurality of groups of holes coaxially and annularly arranged with each other are increased or decreased along the radial direction.

63. The tube of claim 57, wherein the plurality of holes comprises a center hole located at a center or center of the second end and a plurality of peripheral holes located at a periphery of the center hole;

Preferably, the plurality of peripheral holes are arranged in an annular shape, preferably, the plurality of peripheral holes are arranged in a coaxial annular shape around the central hole;

The peripheral holes are provided with a plurality of groups, each group of peripheral holes are annularly arranged, and preferably, the plurality of groups of peripheral holes are coaxially and annularly arranged around the central hole;

preferably, the aperture of the central aperture is different from the aperture of the plurality of peripheral apertures.

64. An injection head for a multi-mode fluid delivery device, the injection head comprising one or more needle members and a support for supporting the needle members.

65. The injector head of claim 64, wherein the support has a first side and a second side opposite the first side;

optionally, the needle member comprises a first needle portion at a first side of the support portion;

Optionally, the needle member includes a fixing pad on the second side of the supporting portion, the fixing pad being used for fixing the needle member;

optionally, the needle member comprises a second needle portion on a second side of the support portion;

Alternatively, the second needle portion of the needle member does not extend from the second side of the support portion, such that the second side of the support portion forms a needleless micropore.

66. The injector head of claim 64 wherein,

Optionally, the first needle portion of the needle member is sharpened and the second needle portion of the needle member is flat;

optionally, both the first and second needle portions of the needle member are sharpened.

67. The injector head of claim 64, wherein said one or more needle members have different adjustable skin insertion depths;

preferably, at least one of the one or more needle members has an insertion depth that does not substantially insert but that is in intimate contact with human or animal skin;

preferably, at least one of the one or more needle members has an insertion depth that is substantially inserted into the inner layer of the human or animal skin;

preferably, at least one of the one or more needle members has an insertion depth that is substantially into the subcutaneous layer of the human or animal body;

Preferably, at least one of the one or more needle members has an insertion depth that is substantially inserted into a muscle layer of a human or animal;

Preferably, at least one of the one or more needle members has an insertion depth of substantial insertion into an organ in a human or animal body;

preferably, at least one of the one or more needle members has an adjustable depth of insertion.

68. The injection head of claim 64 wherein the plurality of needle members comprises a first needle member;

preferably, the first needle member has a first needle aperture sized such that the fluid jet passing through the first needle member is dispersed in one of the dermis, epidermis, subcutaneous, muscle and body organ.

69. The injection head of claim 64 wherein the plurality of needle members comprises a first needle member and a second needle member;

Preferably, the first needle member has a first skin insertion depth in one of a dermis layer, an epidermis layer, a subcutaneous layer, a muscle and a human organ, and the second needle member has a second skin insertion depth in the other of the dermis layer, the epidermis layer, the subcutaneous layer, the muscle and the human organ;

Preferably, the first needle member has a first needle aperture sized to disperse a fluid jet through the first needle member in at least one of the dermis, epidermis, subcutaneous, muscle and human organ, and the second needle member has a second needle aperture sized to disperse a fluid jet through the second needle member in at least one other of the dermis, epidermis, subcutaneous, muscle and human organ.

70. The injection head of claim 69 wherein the plurality of needle members further comprises a third needle member;

preferably, the third needle member has a third skin insertion depth in one of the dermis layer, epidermis layer, subcutaneous, muscle and human organ;

Preferably, the third needle member has a third needle aperture sized such that the fluid jet passing through the third needle member is dispersed in at least one of the dermis layer, epidermis layer, subcutaneous layer, dermis layer, epidermis layer or subcutaneous layer of muscle and human organ.

71. The injector head of claim 64, wherein said plurality of needle members are aligned in a straight line;

preferably, the plurality of needle members are arranged in a straight line along the diameter or the center line of the injection head, and preferably, one of the plurality of needle members arranged in a straight line along the diameter or the center line of the injection head is positioned at the center or the center of the injection head;

Preferably, the plurality of needle members arranged in a straight line are arranged at equal intervals;

preferably, the plurality of needle members aligned in a straight line are mirror-symmetrical with respect to a diameter or midline of the injection head;

preferably, the needle members have a plurality of sets, each set of needle members being arranged along a straight line, preferably each set of needle members being arranged along a diameter or a midline of the injection head;

the plurality of needle members are arranged in an array, preferably the first and second mutually perpendicular diameters or midlines of the plurality of needle members in the array are respectively mirror-symmetrical with respect to the end face of the injection head.

72. The injector head of claim 71, wherein the injector head comprises,

The skin insertion depth of the needle piece located at the center or center of the injection head is different from the skin insertion depth of the other needle pieces of the plurality of needle pieces;

Preferably, the skin insertion depth of at least one of the plurality of sets of needle members is different from the skin insertion depth of the other sets of needle members;

Preferably, the needle aperture of the needle member located at the center or centre of the injection head is different from the needle apertures of the other needle members of the plurality of needle members;

Preferably, the needle apertures of at least one of the plurality of sets of needle elements are different from the needle apertures of the other sets of needle elements.

73. The injector head of claim 64, wherein said plurality of needle members are arranged in an annular configuration;

preferably, the plurality of needle head pieces are annularly arranged with the center of the injection head or the center as the center of the circle;

the needle members have a plurality of sets, each set being arranged in an annular pattern, preferably the plurality of sets being arranged in an annular pattern coaxially with one another.

74. The injector head of claim 73, wherein the injector head comprises,

At least one of the plurality of needle members in the annular array has a skin insertion depth that is different from the other needle members;

preferably, the skin insertion depth of at least one of the plurality of sets of needle members is different from the skin insertion depth of the other sets of needle members;

preferably, the skin insertion depths of the plurality of sets of needle assemblies arranged coaxially and annularly with each other are radially decreasing or increasing;

Preferably, at least one of the plurality of needle members in the annular array has a needle aperture different from the other needle members;

preferably, the needle apertures of at least one of the plurality of sets of needle elements are different from the needle apertures of the other sets of needle elements;

preferably, the needle apertures of the plurality of sets of needle assemblies arranged coaxially and annularly with each other decrease or increase radially.

75. The injector head of claim 64, wherein said plurality of needle members comprises a central needle member positioned at a center or center of said injector head and a plurality of peripheral needle members positioned at a periphery of said central needle member;

preferably, said plurality of peripheral needle members are arranged in an annular pattern, preferably said plurality of peripheral needle members are arranged in a coaxial annular pattern around said central needle member;

The peripheral needle members have a plurality of sets, each set of peripheral needle members being arranged in an annular pattern, preferably the plurality of sets of peripheral needle members being arranged in a coaxial annular pattern about the central needle member.

76. The injector head of claim 75, wherein the injection device comprises a syringe,

The skin insertion depth of the central needle member is different from the skin insertion depth of the plurality of peripheral needle members;

preferably, the skin insertion depth of at least one set of peripheral needle members of said plurality of sets of peripheral needle members is different from the skin insertion depth of the other peripheral sets of needle members;

Preferably, the skin insertion depth of said plurality of sets of needle members and said central needle member coaxially and annularly arranged with respect to each other decreases or increases radially;

preferably, the needle apertures of the central needle member are different from the needle apertures of the plurality of peripheral needle members;

Preferably, the needle apertures of at least one set of peripheral needle members of said plurality of sets of peripheral needle members are different from the needle apertures of the other peripheral sets of needle members;

preferably, the needle apertures of said plurality of sets of needle members and said central needle member, coaxially and annularly arranged with respect to each other, are radially increasing or decreasing.

77. The injection head of claim 64 wherein the needle member further comprises an interventional soft needle removably connected to the bore.

78. The injection head of claim 64 further comprising a needle hub portion sleeved on the needle member and a rotating member operatively connected to the needle member or needle hub portion, the rotating member configured to adjust the axial position of the needle member and needle hub portion by rotation to adjust the exposed length of the needle member relative to the needle hub portion.

79. The injector head of claim 78, wherein the axial positions of the needle member and the hub portion are configured to be adjustable between a plurality of positions such that the exposed length of the needle member is adjustable between a plurality of positions, preferably the exposed length of the needle member is adjustable between a plurality of positions retracted from the hub portion, flush with the hub portion, in the dermis layer, in the epidermis layer, subcutaneously, in the muscle, in a human organ;

preferably, the axial positions of the needle member and the needle hub are configured to be continuously adjustable such that the exposed length of the needle member is continuously adjustable.

80. A needle set for a multi-mode fluid delivery device, characterized in that,

The needle assembly includes one or more needle sleeves, wherein the needle sleeves are configured to removably enclose a first needle portion of a needle member.

81. The needle kit of claim 80, wherein the needle sleeve has a height greater than or equal to the first needle portion of the needle piece so as to completely surround the first needle portion;

Optionally, the needle sleeve of the needle set has a height less than the first needle portion of the needle member, thereby partially surrounding the first needle portion such that the first needle portion protrudes from the needle sleeve front end to form an insert.

82. The needle assembly of claim 80, wherein the needle assembly comprises a first needle assembly having a needle sleeve with a height greater than the first needle portion of the needle assembly to completely enclose the first needle portion to protect the first needle portion.

83. The needle assembly of claim 80, wherein the plurality of needle assemblies, preferably the plurality of needle assemblies comprises a first needle assembly and a second needle assembly,

The first needle set is configured such that it surrounds the first needle portion with one of a partially surrounded, insertion site located in the dermis layer, in the epidermis layer, subcutaneously, in the muscle, or in a human organ;

The second needle set is configured such that it surrounds the first needle portion with the other one of partially surrounded, inserted at the dermis layer, at the epidermis layer, subcutaneously, in muscle or in an organ of the human body.

84. A needle set according to claim 80, wherein the needle set is a plurality, preferably the plurality of needle sets comprises a first needle set, a second needle set, a third needle set, a fourth needle set, a fifth needle set and a sixth needle set;

The first needle set is configured such that it surrounds the first needle portion completely surrounded;

the second needle set is configured such that it surrounds the insertion site of the first needle portion in the dermis layer;

The third needle set is configured such that it surrounds the insertion site of the first needle portion in the epidermis layer;

The fourth needle set is configured such that its insertion portion surrounding the first needle portion is subcutaneously;

the fifth needle set is configured such that its insertion portion surrounding the first needle portion is located in the muscle;

the sixth needle set is configured such that an insertion portion thereof surrounding the first needle portion is located in a human organ.

85. Use of the multi-mode fluid delivery device of any one of claims 1 to 26 in the manufacture of a human clinical medical and animal healthcare pharmaceutical formulation for multi-mode fluid delivery drug delivery.

86. The use according to claim 85,

Optionally, the pharmaceutical formulation is a feline triple vaccine;

Optionally, the pharmaceutical formulation is a hepatitis b vaccine;

Optionally, the pharmaceutical formulation is a human pneumonitis vaccine;

Optionally, the pharmaceutical formulation is semaglutin;

Optionally, the pharmaceutical formulation is a rabies vaccine for humans;

Optionally, the pharmaceutical formulation is a rabies vaccine for animals;

optionally, the pharmaceutical formulation is a meningitis vaccine for humans;

optionally, the pharmaceutical preparation is a hand-foot-and-mouth disease vaccine for animals;

optionally, the pharmaceutical formulation is a human new crown vaccine;

optionally, the pharmaceutical formulation is a human hepatitis a vaccine;

optionally, the pharmaceutical formulation is a human kidney syndrome hemorrhagic fever vaccine;

Optionally, the pharmaceutical formulation is a mumps vaccine for human use;

alternatively, the pharmaceutical formulation is a HPV vaccine for human use;

optionally, the pharmaceutical formulation is a human tumor chemotherapeutic;

optionally, the pharmaceutical formulation is a human tumor nuclear medicine therapeutic drug;

alternatively, the pharmaceutical formulation is a human tumor vaccine, including but not limited to a polypeptide vaccine, an mRNA vaccine, a DNA vaccine;

Optionally, the pharmaceutical formulation is a porcine diarrhea bivalent vaccine;

Optionally, the pharmaceutical formulation is a blue-ear inactivated vaccine;

optionally, the pharmaceutical formulation is a foot-and-mouth vaccine;

optionally, the pharmaceutical formulation is a bovine bivalent vaccine;

Optionally, the pharmaceutical formulation is a papanicolaou vaccine;

Optionally, the pharmaceutical formulation is insulin;

Optionally, the pharmaceutical formulation is a botulinum-type cosmetic drug for medical cosmetology.