Detailed Description
Other advantages and effects of the present invention will become apparent to those skilled in the art from the following disclosure, which describes the embodiments of the present invention with reference to specific examples. The invention may be practiced or carried out in other embodiments that depart from the specific details, and the details of the present description may be modified or varied from the spirit and scope of the present invention. It should be noted that, the illustrations provided in the present embodiment merely illustrate the basic concept of the present invention by way of illustration, and only the components related to the present invention are shown in the illustration, rather than being drawn according to the number, shape and size of the components in actual implementation, and the form, number and proportion of each component in actual implementation may be arbitrarily changed, and the layout of the components may be more complex.
In addition, each embodiment of the following description has one or more features, respectively, which does not mean that the inventor must implement all features of any embodiment at the same time, or that only some or all of the features of different embodiments can be implemented separately. In other words, those skilled in the art can implement some or all of the features of any one embodiment or some or all of the combinations of the features of multiple embodiments selectively according to the disclosure of the present invention as possible and depending on design specifications or actual requirements, thereby increasing the flexibility of the implementation of the present invention.
As used in this specification, the singular forms "a", "an" and "the" include plural referents unless the content clearly dictates otherwise. As used in this specification, the meaning of "a plurality of" generally includes two or more unless the content clearly indicates otherwise. As used in this specification, "distal" generally refers to the end that enters the body first, and "proximal" is the end opposite the "distal". As used in this specification, the term "or" is generally employed in its sense including "and/or" unless the content clearly dictates otherwise. It should also be understood that the present invention in various embodiments repeats reference numerals and/or letters. This repetition is for the purpose of simplicity and clarity and does not in itself dictate a relationship between the various embodiments and/or configurations discussed. It will also be understood that when an element is referred to as being "connected" to another element, it can be directly connected to the other element or one or more intervening elements may be present.
Fig. 1 is a schematic structural view of a balloon dilation catheter according to a preferred embodiment of the present invention. As shown in fig. 1, the present embodiment provides a balloon dilation catheter (i.e., a drug delivery device) comprising a catheter body 1 and a balloon 2 fixed on the catheter body 1, wherein a wire-like body 3 is provided on the outer side of the balloon 2, the wire-like body 3 extends from the proximal end to the distal end of the balloon 2 along the outer surface of the balloon 2, and both ends of the wire-like body 3 are connected with the catheter body 1. Specifically, one end of the wire-shaped body 3 is connected with a pipe section of the catheter body 1 located at the distal end side of the balloon 2, and the other end is connected with a pipe section of the catheter body 1 located at the proximal end side of the balloon 2. The string-like body 3 is an elongated member, and the shape of the elongated member is not limited, and may be, for example, a strip, a band, a thread, a sheet, or the like, and the cross section thereof may be square, triangular, or the like. Preferably, the linear body 3 is a circular elongated member, and has less damage to the intima of the vessel wall. The wire-shaped body 3 is made of a medical metal material or a medical polymer material, and the medical polymer material or the medical metal material selected is not particularly required. For example, the medical metal material for producing the wire-like body 3 is at least one of medical stainless steel, medical cobalt-based alloy, medical nickel-titanium alloy, and medical magnesium alloy. For example, the medical polymer material for producing the thread-like body 3 is at least one of polyethylene terephthalate (PET), a block copolymer of polyamide and polyether (Pebax), polypropylene, and polyurethane.
The surface of the wire-shaped body 3 and/or the balloon 2 carries a drug. The manner of disposing the drug on the balloon 2 and/or the wire-like body 3 is not particularly limited, and the drug is prepared by, for example, electrostatic spraying, atomized spraying, dip coating, drip coating, or crystal self-growth. In addition, the drug on the surface of the wire-shaped body 3 and/or the balloon 2 may be a simple drug or a mixture of a drug and a carrier matrix. The agent may be selected according to need, such as antiproliferative, antirestenotic, anti-inflammatory, antibacterial, antitumor, antimitotic, antimetastatic, antithrombotic, antiosteoporosis, antiangiogenic, cytostatic, microtubule inhibiting agents. Drugs include, but are not limited to, rapamycin and its derivatives (including zotarolimus, everolimus, bijective, 7-O-desmethylrapamycin, temsirolimus, delphinidimus, etc.), paclitaxel derivatives, docetaxel, angiostatin, aspirin, acemetacin, dexamethasone, corticosterone, prednisolone, budesonide, estrogens, selective estrogen receptor modulators, hormones, sulfasalazine, 5-fluorouracil, aminopterin, ammonia salicylic acid, escin, antimycosin, arsenic trioxide, aristolochic acid, small bo bases, ginkgolic acid, endostatin, monoclonal antibodies capable of blocking smooth muscle cell proliferation, antibody carcinomatous drugs, doxorubicin, levofloxacin, hydroxycamptothecin, vinca, vincristine, cisplatin, thymidine kinase inhibitor antibiotics (especially actinomycin-D), strontium ranelate, cyclosporin a, cyclosporin C, brefeldin a, bisphosphonates. Further, the drug is preferably one or more of rapamycin, rapamycin derivatives, paclitaxel derivatives. The carrier matrix may be one or more of iopromide, iopamidol, iohexol, shellac, urea, lecithin, polylactic acid, polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), chitosan, gelatin, glucose, polyarginine, tri-n-hexyl Butyrcitrate (BTHC), tween 80, and the like.
The longitudinal axis of the linear body 3 after being unfolded is parallel or not parallel to the longitudinal axis of the balloon 2 after being unfolded. Preferably, the longitudinal axis of the expanded linear body 3 is parallel to the longitudinal axis of the expanded balloon 2, that is, after the balloon 2 is expanded, the linear body 3 is also expanded, and the extending direction of the expanded linear body 3 is parallel to the longitudinal axis of the expanded balloon 2, so that the balloon 2 is not easily affected by the linear body 3 and can be completely opened or contracted, and the use reliability is better. It should also be understood herein that the term "parallel" does not mean that the two (i.e., the wire and balloon) are perfectly parallel. One of ordinary skill in the art will appreciate that in practical applications, a skew between the longitudinal axis of the wire 3 after deployment and the longitudinal axis of the balloon 2 after deployment is permitted.
Next, the working principle of the balloon dilation catheter of this embodiment will be further described with reference to fig. 7 to 9.
As shown in fig. 7, after the balloon dilation catheter is delivered to the lesion position in the blood vessel by a conventional operation means and the position is confirmed to be correct, external gas or liquid is introduced into the balloon 2, so that the balloon 2 is inflated and then dilated, thereby achieving the purpose of dilating the blood vessel 10, and finally, the balloon 2 is effectively attached to the lesion 20 of the blood vessel 10. As shown in fig. 8-10, during the expansion process of the balloon 2, when the wire-shaped body 3 outside the balloon 2 is subjected to the radially outward acting force of the balloon 2, the inner wall of the lesion blood vessel 10 can be further supported, so that the supporting force of the balloon dilation catheter on the lesion blood vessel 10 is enhanced, and the blood vessel dilation effect is better. Meanwhile, the linear body 3 further extrudes the vessel wall through the expansion of the balloon 2, and the extrusion force of the balloon 2 on the vessel wall is increased through the extrusion effect of the linear body 3 and the vessel wall, so that the medicines on the surface of the linear body 3 and/or the balloon 2 can better permeate into the vessel wall, and the release and utilization rate of the medicines are improved. It will be appreciated that in conventional balloon dilation catheters, the balloon surface conforms to the vessel wall, but the balloon surface is smooth and the pressure applied to the vessel wall is limited, so that the drug does not penetrate well into the vessel wall and the drug transfer rate is low. The invention presses the vessel wall through the linear body 3 outside the balloon, increases the acting force of the balloon on the vessel wall, and the acting force promotes the medicine on the balloon 2 and/or the linear body 3 to better permeate into the vessel wall, thereby improving the transfer rate of the medicine. The wire-like body 3 is small in size (preferably, a filament having a cross-sectional height of 0.1mm to 0.35mm, for example, a filament having a diameter of 0.1mm to 0.35 mm), and even if a lesion part of a blood vessel which is brought into contact with the wire-like body is damaged, the damage is slightly safe, and thus, the safety is good.
Further, both ends of the linear body 3 are fixedly connected with the catheter body 1, or one end is connected with the catheter body 1, and the other end is movably connected with the catheter body 1, or both ends of the linear body 3 are movably connected with the catheter body 1. Preferably, one end of the linear body 3 is fixedly connected with the catheter body 1, and the other end of the linear body 3 is movably connected with the catheter body 1, so that the linear body 3 can move along with the expansion and contraction of the balloon 2. It should be understood that when both ends of the wire-like body 3 are fixedly connected to the catheter body 1, the length of the portions of the wire-like body 3 located at the proximal and distal ends of the balloon 2 should ensure a certain elongation so as to prevent the balloon 2 from being constrained by the wire-like body 3 during the expansion, and further, the minimum length of the wire-like body 3 is greater than the length along the one-sided contour line from the proximal end to the distal end of the expanded balloon 2, so that the too short length of the wire-like body 3 is prevented from affecting the expansion of the balloon 2. In this embodiment, in order not to increase the folding size of the balloon 2, but also to increase the reliability of use and reduce the difficulty of manufacture, it is preferable that one end of the wire-like body 3 is movably connected to the catheter body 1 and the other end is fixedly connected to the catheter body 1, and in this case, the wire-like body 3 itself can be moved along with the expansion and contraction of the balloon 2, so that the balloon 2 can be better ensured to be opened, contracted or folded.
Further, as shown in fig. 1, the length of the tube section of the catheter body 1 extending out of the distal end of the balloon 2 is defined as a head 15, the length of the head 15 is not long, and there is a difficulty in designing the movable structure on the head 15, in order to overcome this difficulty, it is preferable that the proximal end 32 of the wire-shaped body 3 is movably connected to the tube section of the catheter body 1 located at the proximal end side of the balloon 2, and the distal end 31 of the wire-shaped body 3 is fixedly connected to the tube section of the catheter body 1 located at the distal end side of the balloon 2. The movable connection between the proximal end 32 of the wire-like body 3 and the catheter body 1 is not limited, and the fixed connection between the distal end 31 and the catheter body 1 is not limited. Further, the distal end 31 of the wire-shaped body 3 is welded with the pipe section (the head 15) of the catheter body 1 at the distal end side of the balloon 2, so that the process is convenient and the manufacturing difficulty is low.
The number of the linear bodies 3 is not particularly limited in the present invention, and may be one or more, and the plurality of linear bodies 3 may be uniformly or unevenly arranged around the longitudinal axis of the balloon 2. As further shown in fig. 2, the number of the linear bodies 3 is more preferably 2 to 6, and the plurality of the linear bodies 3 are uniformly or unevenly distributed, preferably uniformly distributed, around the longitudinal axis of the balloon 2. Herein, the "uniform" or "nonuniform" generally refers to a state of use after deployment.
With continued reference to fig. 1, the catheter body 1 includes an inner tube 11 and an outer tube 12, where the inner tube 11 is inserted into the outer tube 12 and a medium cavity is formed between the inner tube and the outer tube 12, and a gas or a liquid for filling the balloon 2 is introduced into the medium cavity, and the gas or the liquid passes through the medium cavity to enter and exit the balloon 2. The lumen of the inner tube 11 is used for inserting a guide wire. The proximal end of the balloon 2 is connected to an outer tube 12 and the distal end is connected to an inner tube 11. The distal end 31 of the wire-like body 3 is connected, for example welded, to a tube section of the inner tube 11 extending beyond the distal end of the balloon 2. The proximal end 32 of the wire-like body 3 is connected to a tube section of the outer tube 12 adjacent the proximal end of the balloon 2.
As further shown in fig. 3 and 4, the catheter body 1 further includes a connecting sleeve 13, and the connecting sleeve 13 is disposed on one side of the proximal end of the balloon 2 and is sleeved on the outer tube 12. The connecting sleeve 13 is provided with a mounting cavity 14, the proximal end 32 of the linear body 3 is arranged in the mounting cavity 14, and the proximal end 32 of the linear body 3 is movably or fixedly connected with the mounting cavity 14. When the proximal end 32 of the wire-shaped body 3 is fixedly connected with the mounting cavity 14, the connecting sleeve 13 is movably sleeved on the outer tube 12, so that the connecting sleeve 13 can move relative to the balloon 2 (i.e. the outer tube 12). When the proximal end 32 of the wire-shaped body 3 is movably connected with the mounting cavity 14, the connecting sleeve 13 may be movably sleeved on the outer tube 12 or may be fixedly sleeved on the outer tube 12, that is, the connecting sleeve 13 may be movable or fixed, preferably, the connecting sleeve 13 is fixedly arranged at this time.
In some embodiments, as shown in fig. 3, the proximal end 32 of the wire-shaped body 3 is movable in the installation cavity 14, and the connection sleeve 13 is fixedly disposed, when the wire-shaped body is prepared, the proximal end 32 of the wire-shaped body 3 is movably connected with the installation cavity 14 after being inserted into the connection sleeve 13 from one end of the connection sleeve 13 towards the balloon 2, at this time, the axial length of the installation cavity 14 along the outer tube 12 is the movable distance of the wire-shaped body 3, which needs to ensure that the balloon 2 can be smoothly opened or contracted or folded, and at the same time, the opening at one end of the installation cavity 14 can prevent the proximal end 32 of the wire-shaped body 3 from being separated from the connection sleeve 13. Therefore, when the balloon 2 is deployed, the proximal end 32 of the linear body 3 can move in the direction of the balloon 2 (i.e. distally) in the mounting cavity 14, so that the balloon 2 can be completely opened without being constrained by the linear body 3, and meanwhile, the deployed balloon 2 has a radially outward acting force on the linear body 3, so that the linear body 3 is guaranteed to be attached to the vessel wall (i.e. guaranteed to be pressed against the vessel wall), so that the vessel wall is effectively supported, and the proximal end 32 of the linear body 3 is constrained by the mounting cavity 14 and cannot fall off from the mounting cavity 14. And when the balloon 2 is folded, the proximal end 32 of the wire-shaped body 3 can move away from the balloon 2 (namely, the proximal end), but does not exceed the length of the mounting cavity 14, so that the wire-shaped body 3 can not hang over the catheter and the vascular wall. Further, the proximal end of the wire-like body 3 has a size (diameter) slightly larger than the size (diameter) of the remaining portion.
In some embodiments, as shown in fig. 4, the proximal end 32 of the wire-shaped body 3 is not movable in the installation cavity 14, and the connecting sleeve 13 is movably disposed, and during preparation, the proximal end 32 of the wire-shaped body 3 is also inserted into the connecting sleeve 13 from one end of the connecting sleeve 13 facing the balloon 2 and then fixedly connected with the installation cavity 14, at this time, the moving distance of the connecting sleeve 13 along the axial direction of the outer tube 12 is the movable distance of the wire-shaped body 3, which needs to ensure that the balloon 2 can be smoothly opened, contracted or folded. Further, when the proximal end 32 of the wire-shaped body 3 is fixedly connected to the connecting sleeve 13, the connecting sleeve 13 may be connected by heat shrinkage, i.e. the connecting sleeve 13 is designed as a heat shrinkage tube. The working principle of the design is similar to that described above, namely, when the balloon 2 is unfolded, the connecting sleeve 13 moves towards the balloon 2, so that the proximal end 32 of the linear body 3 is driven to move towards the balloon 2, the balloon 2 is ensured to be completely opened, and the proximal end 32 of the linear body 3 is fixed with the mounting cavity 14 and cannot fall off from the mounting cavity 14. When the balloon 2 is folded, the connecting sleeve 13 moves away from the balloon 2, so that the proximal end 32 of the linear body 3 also moves away from the balloon 2, and the folding of the balloon 2 is not affected.
Further, the wire-shaped body 3 is preferably a round filament, which has less damage to the inner membrane of the blood vessel wall, and the diameter of the round filament is preferably 0.10mm to 0.35mm, more preferably 0.15mm to 0.25mm. Further, the diameter of the proximal end portion of the wire-like body 3 is larger than the diameter of the remaining portion, and the diameter of the proximal end portion is 0.12mm to 1.0mm, more preferably 0.17mm to 0.90mm, for example 0.12mm to 0.50mm, and still more preferably 0.17mm to 0.40mm. When the cross section of the linear body 3 is non-circular, the cross section height is preferably 0.10mm to 0.35mm, more preferably 0.15mm to 0.25mm.
Further, the outer surface of the linear body 3 is smooth, and is generally cylindrical (fig. 8), or triangular (fig. 10). Or as shown in fig. 5b and 5c, the outer surface of the side of the linear body 3 facing away from the balloon 4 is rugged, and the rugged surface is used for being attached to the wall of the blood vessel, so that the pressure on the wall of the blood vessel is further increased by the bulges on the surface of the linear body 3, and the medicine is better permeated into the wall of the blood vessel. The present invention is not limited to the shape of the protrusions, including but not limited to a saw tooth shape. Preferably, the protrusions are shaped as saw teeth, such as straight saw teeth of fig. 5b, or inclined saw teeth of fig. 5 c. It will be appreciated that the surface roughness of the wire-like body 3 is configured to have a slight safety damage to the inner wall of the blood vessel, and the safety of use can be ensured. In addition, the oblique saw tooth has the advantages that the catheter can not scratch non-pathological blood vessels when being withdrawn from the blood vessels, and the safety is better. Further, the protrusions may be continuously distributed, such as triangular prisms as shown in fig. 10, or the protrusions may be spaced apart along the length direction of the linear body, such as the saw tooth surfaces shown in fig. 5b and 5 c.
In this embodiment, the balloon dilation catheter has a collapsed state and an expanded state, the balloon dilation catheter being in the expanded state after the balloon 2 has been expanded or inflated, the balloon dilation catheter being in the collapsed state before the balloon 2 has been expanded or inflated. After folding, the number of folding wings 21 of the balloon 2 is at least two, and the folding wings can be arranged at equal angles or different angles. For example, as shown in fig. 6, 3 folding wings 21 of the balloon 2 are arranged at equal angles. Further, when the balloon 2 is folded, the string-shaped body 3 may or may not be wrapped by the folding wings 21. Especially when the number of the linear bodies 3 is plural, all the linear bodies 3 are wrapped by the folding wings 21, or a part of the linear bodies are wrapped, or all the linear bodies are not wrapped. The size of the balloon 2 is not limited, and the balloon is arranged according to actual treatment requirements, for example, in coronary intervention treatment, the diameter of the balloon 2 after being unfolded is preferably 1.5 mm-4.0 mm, and the length of the balloon is preferably 6 mm-40 mm.
With continued reference to fig. 1, the balloon dilation catheter further includes a proximal connector 4 connected to the proximal end of the catheter body 1, specifically to the proximal end of the outer tube 12, and the outer tube 12 may be connected to the proximal connector 4 by a stress diffuser 5. Further, the outer tube 12 includes a proximal outer tube 121 and a distal outer tube 122, and the distal end of the proximal outer tube 121 is connected to the proximal end of the distal outer tube 122. The balloon dilation catheter may be of The coaxial Over The Wire (OTW) or The rapid exchange type (Rapid Exchange System), the specific exchange form is not limited. In this embodiment, a guide wire port 123 is disposed between the proximal outer tube 121 and the distal outer tube 122, and the guide wire is inserted into the inner tube 11 through the guide wire port 123. Further, the inner tube 11 is provided with development marks 6 on a tube section inside the balloon 2, and the development marks 6 are usually two, wherein one development mark 6 corresponds to a proximal position of the balloon 2, and the other development mark corresponds to a distal position of the balloon 2. The developing mark 6 is integrally formed with the inner tube 11, a part of the tube section of the inner tube 11 is made of developing material, or the developing mark 6 is formed separately from the inner tube 11, for example, a developing ring is formed separately, and the developing ring is nested on the inner tube 11. Further, a catheter identification band 124 is provided on the proximal outer tube 121 for marking the length of the balloon dilation catheter into the body.
The balloon dilation catheter of the present invention will be further described in conjunction with experimental data and experimental results to further highlight the features and characteristics of the above-described examples, but should not be construed as limiting the invention in the manner set forth below.
Example 1
Firstly, providing a balloon dilation catheter without medicine, wherein the wire-shaped body is made of filaments, the diameter of the filaments is 0.151mm, the number of the filaments is 2, the filaments are made of medical stainless steel, and the surfaces of the filaments are smooth.
And then preparing a medicinal solution by dissolving the medicinal paclitaxel and the carrier matrix iopromide in a solvent and mixing to obtain the medicinal solution, wherein the solvent is ethanol and water, and the specific formula of the medicinal solution is shown in table 1.
TABLE 1 pharmaceutical solution formulation
And then spraying the surface of the bare balloon provided with the filaments with a drug solution by adopting an atomization spraying mode to obtain the drug-loaded balloon dilation catheter.
Thereafter, the balloon is folded (e.g., balloon folding machine) with the wings of the balloon folding wings 21 being 3-piece and equiangularly aligned, wherein 1 filament is wrapped by the balloon flap 21.
And finally, loading the folded saccule into a protective sleeve for fixation, and sterilizing to obtain the drug-loaded saccule dilating catheter.
Example 2
Firstly, a balloon dilation catheter without medicine is provided, wherein the number of filaments is 3, the diameter of each filament is 0.210mm, the material of each filament is medical stainless steel, and the surface of each filament is in a straight saw tooth shape.
Then preparing a drug solution, namely dissolving the drug rapamycin and the carrier matrix polylactic acid in a solvent, and mixing to obtain the drug solution, wherein the solvent is ethyl acetate, and the specific formula of the drug solution is shown in table 2.
TABLE 2 pharmaceutical solution formulations
| Component (A) | Substance (B) | Concentration of |
| Medicament | Rapamycin (rapamycin) | 4mg/ml |
| Carrier body | Polylactic acid | 4mg/ml |
And then spraying the surface of the bare balloon provided with the filaments with a drug solution by adopting an atomization spraying mode to obtain the drug-loaded balloon dilation catheter.
Thereafter, the balloon is folded, the wings of the balloon folding wing 21 being 3-piece and equiangularly arranged, wherein all filaments are wrapped by the balloon flap.
And finally, loading the folded saccule into a protective sleeve for fixation, and sterilizing to obtain the drug-loaded saccule dilating catheter.
Example 3
A balloon dilation catheter without carrying a drug is provided, wherein the number of filaments is 4, the diameter of the filaments is 0.160mm, the material of the filaments is polyethylene terephthalate (PET), and the surfaces of the filaments are smooth.
And then preparing a medicinal solution by dissolving the medicinal paclitaxel and the carrier matrix iopromide in a solvent and mixing to obtain the medicinal solution, wherein the solvent is ethanol and water, and the specific formula of the medicinal solution is shown in table 1.
And then spraying the surface of the bare balloon provided with the filaments with a drug solution by adopting an atomization spraying mode to obtain the drug-loaded balloon dilation catheter.
Thereafter, the balloon is folded, the wings of the balloon folding wing 21 being 4-piece and equiangularly arranged, wherein all filaments are wrapped by the balloon flap.
And finally, loading the folded saccule into a protective sleeve for fixation, and sterilizing to obtain the drug-loaded saccule dilating catheter.
Example 4
Firstly, preparing a medicinal solution, namely dissolving the medicinal paclitaxel and the carrier matrix iopromide in a solvent, and mixing to obtain the medicinal solution, wherein the solvent is ethanol and water, and the specific formula of the medicinal solution is shown in table 1.
Then, 4 filaments are selected, the diameter of each filament is 0.210mm, the filament material is a segmented copolymer (Pebax) of polyamide and polyether, and an atomization spraying mode is adopted to spray medicine solution on the surface of each filament, so that medicine carrying filaments are obtained.
After the drug-loaded filaments are obtained, preparing the balloon dilation catheter, wherein the filaments are the drug-loaded filaments, the number of the filaments is 4, and the surfaces of the filaments are straight saw teeth.
Thereafter, the balloon is folded, the wings of the balloon folding wing 21 being 4-piece and equiangularly arranged, wherein all filaments are wrapped by the balloon flap.
And finally, loading the folded saccule into a protective sleeve for fixation, and sterilizing to obtain the drug-loaded saccule dilating catheter.
Example 5
Firstly, preparing a medicinal solution, namely dissolving the medicinal paclitaxel and the carrier matrix iopromide in a solvent, and mixing to obtain the medicinal solution, wherein the solvent is ethanol and water, and the specific formula of the medicinal solution is shown in table 1.
Then, 3 filaments are selected, the filaments are made of medical cobalt-based alloy, and the surface of the filaments is sprayed with a drug solution in an atomization spraying mode to obtain drug-loaded filaments.
After the drug-loaded filaments are obtained, preparing the balloon dilation catheter, wherein the filaments are the drug-loaded filaments, the diameter of the filaments is 0.155mm, the number of the filaments is 3, and the surfaces of the filaments are smooth.
Thereafter, the balloon is folded, the wings of the balloon folding wing 21 being 3-piece and equiangularly arranged, wherein all filaments are wrapped by the balloon flap.
And finally, loading the folded saccule into a protective sleeve for fixation, and sterilizing to obtain the drug-loaded saccule dilating catheter.
Example 6
Firstly, preparing a medicinal solution, namely dissolving the medicinal paclitaxel and the carrier matrix iopromide in a solvent, and mixing to obtain the medicinal solution, wherein the solvent is ethanol and water, and the specific formula of the medicinal solution is shown in table 1.
Then, spraying the medicine solution on the surface of the balloon by adopting an atomization spraying mode to obtain the medicine carrying balloon.
After the drug-loaded saccule is obtained, a saccule dilating catheter is prepared, wherein the filaments have no drug-loaded coating, the number of the filaments is 3, the diameter of the filaments is 0.245mm, the filaments are made of medical cobalt-based alloy, and the surfaces of the filaments are beveled saw teeth.
Thereafter, the balloon was folded with the wings of the balloon folding wings being 3-piece and equiangularly aligned, wherein all filaments were wrapped by the balloon flaps.
And finally, loading the folded saccule into a protective sleeve for fixation, and sterilizing to obtain the drug-loaded saccule dilating catheter.
Example 7
The preparation method comprises the steps of dissolving rapamycin and polylactic acid serving as a carrier matrix in a solvent, and mixing to obtain a medicinal solution, wherein the solvent is ethyl acetate, and the specific formula of the medicinal solution is shown in table 2.
Then, spraying the medicine solution on the surface of the balloon by adopting an atomization spraying mode to obtain the medicine carrying balloon.
After the drug-loaded balloon is obtained, the balloon dilation catheter is prepared, wherein the filaments are free of drug-loaded coating, the diameter of the filaments is 0.105mm, the number of the filaments is 4, the filament material is a segmented copolymer (Pebax) of polyamide and polyether, and the surface of the filaments is smooth.
Thereafter, the balloon is folded with the wings of the balloon folding wings being 4-piece and equiangularly aligned, wherein all filaments are wrapped by the balloon flaps.
And finally, loading the folded saccule into a protective sleeve for fixation, and sterilizing to obtain the drug-loaded saccule dilating catheter.
Example 8
Firstly, providing a balloon dilation catheter without medicine, wherein the number of filaments is 3, the diameter of the filaments is 0.349mm, the material of the filaments is medical cobalt-based alloy, and the surface of the filaments is a bevel saw tooth type.
Then preparing a drug solution, namely dissolving the drug rapamycin and the carrier matrix lecithin in a solvent, and mixing to obtain the drug solution, wherein the solvent is ethanol, and the specific formula of the drug solution is shown in table 3.
Table 3 pharmaceutical solution formulations
| Component (A) | Substance (B) | Concentration of |
| Medicament | Rapamycin (rapamycin) | 5mg/ml |
| Carrier body | Lecithin | 5mg/ml |
And then spraying the surface of the bare balloon provided with the filaments with a drug solution by adopting an atomization spraying mode to obtain the drug-loaded balloon dilation catheter.
Thereafter, the balloon was folded with the wings of the balloon folding wings being 3-piece and equiangularly aligned, wherein all filaments were wrapped by the balloon flaps.
And finally, loading the folded saccule into a protective sleeve for fixation, and sterilizing to obtain the drug-loaded saccule dilating catheter.
Example 9
The preparation method comprises the steps of dissolving rapamycin and lecithin as a carrier matrix in a solvent, and mixing to obtain a medicinal solution, wherein the solvent is ethanol, and the specific formula of the medicinal solution is shown in Table 3.
Then, spraying the medicine solution on the surface of the balloon by adopting an atomization spraying mode to obtain the medicine carrying balloon.
After the drug-loaded saccule is obtained, a saccule dilating catheter is prepared, wherein the filaments have no drug-loaded coating, the number of the filaments is 4, the diameter of the filaments is 0.250mm, the filaments are made of medical cobalt-based alloy, and the surfaces of the filaments are straight saw teeth.
Thereafter, the balloon is folded with the wings of the balloon folding wings being 4-piece and equiangularly aligned, wherein all filaments are wrapped by the balloon flaps.
And finally, loading the folded saccule into a protective sleeve for fixation, and sterilizing to obtain the drug-loaded saccule dilating catheter.
Example 10
Animal experiments were performed on the above examples, and the resulting tissue blood vessel drug concentrations are shown in table 4.
In addition, the animal experiment is further added with a control example 1 and a control example 2:
comparative example 1, the filament diameter was 0.710mm, the remainder being the same as in example 1;
comparative example 2, the filament diameter was 0.653mm, and the remainder was the same as in example 2.
1) Experimental details
Healthy domestic white pigs were selected as animal models, balloon dilation catheters were implanted into the coronary arteries, and drug release profile and overall instrument safety at different time points after implantation were evaluated.
2) Experimental results
The safety of the drug balloon loaded with the filaments was evaluated first, and it was found from the observation in laboratory pigs and after the operation that the balloon dilation catheters in examples 1 to 9 had little damage to the intima of the vessel wall without significant damage, whereas the balloon dilation catheters in comparative example 1 and comparative example 2 had significant tearing of the intima of the vessel wall, probably due to excessive extrusion of the vessel wall due to excessive filament diameter. Therefore, the size of the linear body is reasonably controlled, so that slight damage can be ensured to only occur at the extrusion point, serious damage can not be caused to the inner membrane of the blood vessel wall, and the middle membrane of the blood vessel wall can be kept intact without obvious damage. The balloon dilation catheter of the present invention is safe to use.
Next, the drug concentration in the tissue blood vessel was evaluated, as shown in Table 4.
TABLE 4 concentration of drug in tissue vessels (Unit: μg/g)
As can be seen from Table 4, the balloon dilation catheter of the present invention has an effective drug release effect and a high drug transfer rate. More specifically, in examples 1 to 3, both the balloon surface and the filament surface were sprayed with the drug, and the filament surface in example 2 was straight saw tooth shaped, the drug concentration in the tissue was relatively higher compared to the filament with smooth surface. In examples 4 and 5, the surface of the balloon was not coated with drug, and only the surface of the filaments was coated with drug, and the surface of the filaments in example 4 was straight saw tooth-shaped, and the concentration of drug in the tissue was relatively higher than that of the filaments with smooth surfaces. In examples 6, 7 and 9, the surface of the balloon was coated with the drug, the surface of the filaments was not coated with the drug, the surface of the filaments in example 6 was beveled, the surface of the filaments in example 9 was straight-saw-tooth, and the concentration of the drug in the tissue was relatively higher than that of the smooth-surfaced filaments. Therefore, the medicines on the surfaces of the filaments and/or the sacculus 2 can better permeate into the blood vessel wall along with the extrusion of the filaments and the blood vessel wall, the transfer and utilization rate of the medicines are high, and the treatment effect of the medicines is better.
In summary, the balloon dilation catheter of the invention loads the medicine through the linear body, improves the medicine loading capacity, and particularly, the medicine on the surface of the linear body and/or the surface of the balloon can better permeate into the vessel wall along with the extrusion of the linear body and the vessel wall, so that the medicine can better play a role, effectively prevent intimal hyperplasia and reduce the probability of restenosis. In addition, the balloon with the linear body on the surface is used for safely and effectively supporting the diseased vessel wall, so that the damage such as intimal tearing, interlayer and acute occlusion can be avoided, and the safety is better.
The above description is only illustrative of the preferred embodiments of the present invention and is not intended to limit the scope of the present invention, and any alterations and modifications made by those skilled in the art based on the above disclosure shall fall within the scope of the present invention.