US20020174864A1 - Nasal delivery device including spray nozzle - Google Patents

Abstract

A nasal delivery device is provided for delivering substances such as liquid drugs, vaccines and the like to a nasal passage. The nasal delivery device preferably comprises a drug container such as syringe and a separable spray nozzle. The spray nozzle includes a rigid plastic cap having a spray aperture at a distal end of the nozzle for delivering the liquid substance to the nasal passage. Attachment means is provided for attaching the spray nozzle to the syringe at the time of the delivery of the liquid substance to the nasal passage. The nozzle defines a conduit that allows fluid communication from the syringe to the spray aperture. The nozzle includes an internal valve between the spray aperture and the syringe for allowing only pressurized liquid substance to flow through the conduit and the aperture so that a mist or spray is delivered through the spray aperture.

Description

FIELD OF THE INVENTION
• The present invention generally relates to delivery systems for delivering substances such as drugs, vaccines and the like, and more specifically relates to a delivery device for delivering such substances intranasally, i.e., through the nose, including a spray nozzle for use with a prefilled drug container such as a syringe. In addition, the present invention relates to a nasal delivery device and more particularly to a removable spray nozzle for use with standard syringes.[0001]
BACKGROUND OF THE INVENTION
• Many injectable drugs are packaged and distributed in hypodermic syringes that will eventually be used to administer the drug to the patient. The syringe is the low cost, efficient, sterile instrument of choice for delivering liquid drug through a hypodermic needle. The hypodermic syringe also can be an excellent storage device for drug placed in it by a pharmaceutical manufacturer or hospital pharmacy.[0002]
• Syringes may also prove useful for distributing and administering drugs even where a hypodermic injection is not desired. Delivering a therapeutic liquid as a spray through the nasal passageway is preferred to deliver certain therapeutic liquids under certain conditions. There have been several proposed devices to make syringes useful as nasal sprayers.[0003]
• U.S. Pat. No. 5,601,077 to Imbert discloses a nasal syringe sprayer for discharging the liquid contents of the syringe in a spray through the nasal passages. However, the use of that device is limited to pre-stored, liquid stable drugs. That is, the sprayer of the patent cannot be used with drugs that need to be maintained in powder or lyophilized form and reconstituted just prior to intake. Additionally, the sprayer tip of that patent does not allow an individual to load the syringe with a liquid mediation from a standard vial since the nasal spray nozzle cannot be inserted into such vials to extract the contents of the vial for loading the syringe.[0004]
• U.S. Pat. No. 4,767,416 to Wolf et al. discloses a flexible, removable spray nozzle for a syringe. The spray nozzle may be attached directly to a luer fitting of a syringe or may be adapted to fit over and attached to a hypodermic needle secured to the luer fitting. In either case, the spray nozzle fits onto the syringe in order to prevent back flow and leakage of the liquid at the attachment of the spray nozzle to the syringe. One shortcoming of the device is that the nozzle does not prevent unpressurized liquid from flowing through the opening at the tip of the spray nozzle.[0005]
• In view of the shortcomings and drawbacks of currently available or proposed systems, it is desirable to provide a removable spray nozzle for use with hypodermic syringes that provides a leak-free seal and prevents unpressurized liquid from flowing out the opening at the spray nozzle.[0006]
SUMMARY OF THE INVENTION
• In contrast to the prior devices discussed above, it has been found that a nasal delivery device particularly suited for use in intranasally delivering substances such as drugs, vaccines and the like can be constructed in accordance with the present invention. Specifically, the invention is directed to a nasal delivery device having a removable spray nozzle adapted for delivering liquid substances such as a drug from a syringe to a nasal passage. The spray nozzle includes a plastic rigid cap having a spray aperture at one end of the nozzle for delivering the liquid substance to the nasal passage. The spray nozzle is attached to the syringe when delivery of the liquid substance will be sprayed into the nasal passage. The spray nozzle includes an internal valve that allows pressurized liquid substance to flow through the nozzle and out of the spray aperture while also preventing unpressurized liquid from flowing through the spray aperture.[0007]
• In the preferred embodiment, the spray nozzle has a flange at a proximal end to prevent an individual from over-inserting the nozzle into the nasal passage. The nozzle may also include a resilient, elongate sleeve extending from the nozzle that is received over an elongate barrel of the syringe. The elongate sleeve includes a flange at an end to aid a user in grasping the assembly and delivering the liquid from the syringe to the nasal passage.[0008]
• The various features and advantages of this invention will become apparent to those skilled in the art from the following detailed description of the currently preferred embodiments. The drawings that accompany the detailed description can be briefly described as follows.[0009]
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1 is a perspective view of a nasal delivery device designed according to this invention.[0010]
• FIG. 2 is a side elevation view of the nasal delivery device of FIG. 1.[0011]
• FIG. 3 is a side elevation view of the nasal delivery device of FIG. 1 viewed from the one end.[0012]
• FIG. 4 is a partial cross-sectional view of the nasal delivery device of FIG. 3 taken along line[0013]4-4.
• FIG. 5 is a cross-sectional view of the nasal delivery device of FIG. 2 taken along line[0014]5-5.
• FIG. 6 is an enlarged cross-sectional view of the spray nozzle of the nasal delivery device illustrating a two-component spray nozzle assembly having one-way valve features.[0015]
• FIG. 7 is an enlarged cross-sectional view of the spray nozzle illustrating a snap-fit feature.[0016]
• FIG. 8 is a side elevational view of an alternative embodiment of a nasal delivery device designed according to this invention.[0017]
• FIG. 9 is a flow chart diagram schematically illustrating a method of filling a device designed according to this invention.[0018]
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
• FIGS.[0019]1-6 illustrate the nasal delivery device of the present invention generally designated20 including a drug container such as a standard syringe and aseparable spray nozzle37 attachable thereto. The syringe has anelongated barrel21 having an openproximal end22, achamber23 for retaining liquid and atip portion25 extending from adistal end27 of thebarrel21. Apassageway28 extends through thetip portion25 between thechamber23 and an opening in the end of the tip portion.
• For the purposes of this description, the term “distal end” is used to refer to the end furthest from the person holding the nasal delivery device and the term “proximal end” is meant to refer to the end closest to the holder of the nasal delivery device.[0020]
• A[0021]stopper29 is slidably positioned in fluid-tight engagement insidebarrel21 and is connected to anelongate plunger rod31 in a conventional manner. Theplunger rod31 projects proximally from thestopper29 and extends outwardly from the openproximal end22 of thebarrel21. Theplunger rod31 is accessible outside of the proximal end of the barrel and is provided to move thestopper29 along thebarrel21 to force liquid out of thechamber23 through thepassageway28. A disc-shapedplunger rod flange32 on the proximal end of theplunger rod31 provides a convenient structure for applying forces to move theplunger rod31 with respect to thebarrel21. The large surface area of theflange32 reduces the pressure on a user's fingers while delivering the substance such as a drug, vaccine or the like through the nasal delivery device.
• A therapeutic liquid such as[0022]liquid substance35 is contained within thechamber23. The syringe can be prefilled or manually filled by an end user as needed. An example method of prefilling is discussed below in connection with FIG. 9. In the event that the user fills the syringe, that should be completed before thespray nozzle37 is in place.
• In order to deliver the[0023]liquid substance35 to the nasal passage of a user, theseparable spray nozzle37 slides onto thetip25 of thesyringe20. The internal surface of thespray nozzle37 defines aconduit39 that is in fluid communication with thepassageway28 when placed on the syringe. Thespray nozzle37 also includes adistal end40 having aspray aperture41 in fluid communication withconduit39.
• The[0024]spray nozzle37 preferably includes two main components; a generally rigidplastic cap38 and a generallyflexible valve45. Thecap38 preferably is constructed of a polymer, such as polypropylene, and is configured to be slidably mounted onto thetip portion25 of thebarrel21 of the syringe. A conventional luer tip arrangement between thetip portion25 and acooperating opening44 of thecap38 secure thecap38 in place.
• A variety of cap openings and tip configurations can be used. It is useful to use tip designs that differ from conventional syringes when it is important to ensure that a standard hypodermic needle will not be used with a syringe body intended for use with the[0025]spray nozzle37 of the present invention.
• The[0026]valve45 preferably is contained within thecap38 between thetip portion25 and thedistal end40 of thecap38. Thevalve45 interacts with the internal surface ofcap38 to allow only pressurized liquid to flow distally through thespray aperture41. Thevalve45 prevents unpressurized liquid in thechamber23 from flowing through theaperture41. Therefore, a mist of liquid rather than a stream or drops are expelled from theoutlet41.
• The valve in one preferred embodiment is a skirt valve having a[0027]circumferential skirt46 that will partially collapse or move away from the internal sidewall under the force of pressurized liquid from thechamber23 to allow the liquid to flow from the syringe through thespray aperture41. Theskirt46 collapses by moving away from the interior side wall of thecap38 allowing liquid to pass through the gap, which is created by hydraulic pressure, between theskirt46 and thecap38. Since theskirt46 is normally biased into engagement with the internal sidewall and only flexes in one direction, it ensures that no fluid flows in a backward direction through the cap. A wide variety of materials such as natural rubber, synthetic rubber and thermoplastic elastomers are suitable for forming theflexible valve45 with thermoplastic elastomers being preferred.
• The[0028]spray nozzle37 preferably includes aflange43 at a proximal end of thecap38.Flange43 acts as a depth limiter to prevent over-insertion of thenozzle37 into the nasal passage.
• As shown in FIG. 7, the[0029]spray nozzle37 may be configured so that it may not be removed from the syringe. In this embodiment, thetip25 of the syringe has agroove60 that preferably extends circumferentially around the tip portion adjacent the syringe body. Cooperatingopening44 has a corresponding undercut62 that forms a flange so that when thecap38 is slid onto thetip25, a snap-fit between the flange and groove effectively permanently secures thenozzle37 to the syringe. Thevalve45 is not illustrated in FIG. 7 for simplification. A valve preferably is included to ensure that a mist or spray is delivered into a nasal passage.
• In some instances, it is useful to permit some flow back into the syringe through the spray nozzle. For example, FIG. 7 includes a modified[0030]valve45′ that has at least one passage46athrough theskirt46. This passage allows fluid to be drawn into the syringe when using an appropriately configured vial adapter.
• As best seen in FIGS. 2, 4 and[0031]5, adosage limiter47 can be employed. Thelimiter47 partially surrounds theplunger rod31 so that thelimiter47 will not fall off theplunger rod31 under its own weight but may be forcibly removed from theplunger rod31 without eliminating the ability of the nasal delivery device to deliver the substance from the chamber through theaperture41. Thelimiter47 may be designed with a thin cross-section so that it will deflect and snap over theplunger rod31 or theplunger rod31 may be designed to deflect under the forces of thelimiter47 during attachment or removal. Alternatively, both elements may be designed to deflect partially during installation and removal of thelimiter47. Afinger tab portion49 facilitates installation and removal. A plurality ofribs50 provide a better grip.
• The[0032]limiter47 is adapted to interact between a radially extending projection on theplunger rod31 such asflange32 andproximal end22 of thebarrel21 which includes a barrel flange26 to limit the distal motion of the plunger rod with respect to thebarrel21. For example, the length of thelimiter47 can correspond to one-half of the volume of liquid substance in thechamber23, which proves useful to deliver equal doses into each nostril.
• In use, the nasal delivery device can be inserted into one nostril of the user while it is fully loaded such as illustrated in FIG. 4. Pressure on the[0033]plunger rod flange22 in a distal direction (i.e., right to left according to the drawing) will cause theliquid substance35 to flow through thepassageway28 into theconduit39 of thecap38, deflecting theskirt portion46 of theflexible valve45, and through thespray aperture41. Theplunger rod31 can be moved until further distal motion is prevented by contact of theplunger rod flange32 withlimiter47 which, in turn, contacts barrel flange26. Theplunger rod31 can no longer be moved in a distal direction and approximately one-half of the liquid substance still remains in the syringe.
• The user then removes the nasal delivery device from one nostril, pulls the[0034]limiter47 off theplunger rod31 and prepares to deliver a dose to the other nostril. With thelimiter47 now removed, the nasal delivery device may now be placed so that the spray nozzle is in the other nostril and the remaining half of theliquid substance35 may be delivered.
• An alternative embodiment[0035]nasal delivery device55 is illustrated in FIG. 8. In this embodiment, the structure of the nasal delivery device is substantially similar to the nasal delivery device of the embodiment of FIGS.1-7. Accordingly, substantially similar components that perform substantially similar functions will be numbered identically to the components of the embodiment of FIGS.1-7 except a suffix “a” will be used to identify those components in FIG. 8.
• In this alternate embodiment, the[0036]spray nozzle37 preferably includes a generally resilient,elongate sleeve member64 extending from thecap38a.Elongate sleeve member64 may be a unitary sleeve member that fully surrounds the syringe body or may include two finger-like portions66, as shown in FIG. 8. Aflange68 provides an increased surface area to aid a user in delivering the liquid from the syringe to the nasal passage. The increased surface area is more easily retained against an individual's index and fore fingers than thetypical end22aof the syringe body. Additionally, pressure from the individual's fingers serves to maintain thenozzle37 on the syringe.
• The embodiment of FIG. 8 preferably includes a valve member in the[0037]cap portion38aas described above to ensure a spray or mist delivery. Theadapter37acan include the snap fit shown in FIG. 7.
• There are several advantages provided by the present invention. The inventive arrangement having a nasal sprayer adapter can be used to deliver the substance that is targeted for nasal delivery but is not liquid-stable and, therefore, needs to be stored in powder or lyophilized form in a separate, appropriate vial. Other nasal delivery device devices that do not have a cap like that of this invention cannot accommodate such substances.[0038]
• Less water vapor is lost from a syringe that works with the inventive adapter since the plastic cap need not be permanently attached to the syringe prior to use. Additionally the likelihood for pressure valve activation during plunger rod assembly and handling is lessened since the spray nozzle need not be attached to the syringe until it is ready for use. Furthermore, stability testing regarding compatibility issues is simplified since the plastic spray nozzle does not interfere with the liquid substance over a long period of time.[0039]
• The advantages provided by this invention render it more useful for use with prefilled syringes. One method of prefilling syringes to be used as a nasal delivery device is schematically shown in flow chart form in FIG. 9.[0040]
• A supply of syringe barrels[0041]200 includes the desired form of syringe, such as those illustrated and discussed above. A locally controlledenvironment202 preferably is maintained in a known manner. The locally controlledenvironment202 preferably is situated to immediately accept the syringes without requiring any intermediate cleaning or sterilizing steps between thesupply200 and theenvironment202.
• In one example, the syringe barrels are washed with air at[0042]204 to remove any particulates from the syringes. The syringes preferably are then coated at206 with a lubricant such as a lubricating silicone oil on the inner surface. The lubricant facilitates moving thestopper29 andplunger rod31 through the syringe during actual use of the device.
• The end of syringes that eventually receive the spray nozzle may be capped with a tip cap within the[0043]environment202. In one example, tip caps are supplied at208. The tip caps are air washed at210. The cleaned tip caps and syringe barrels are conveyed to anassembly device212 where the tip caps are secured onto the syringes. The syringe barrel assemblies are then conveyed to afilling station214 to be filled with the desired substance.
• Once filled as desired, the[0044]stoppers29 are inserted into the open end of the syringes at220. Prior to inserting thestoppers29, they preferably are assembled with theplunger rods31 at222 and lubricated at224 with a conventional lubricant in a known manner. The assembled, filled syringes preferably are inspected at226 for defects and discharged from the locally controlled environment.
• The syringes typically will be sterilized at[0045]230 and packaged at232 into individual packages or into bulk packaging depending on the needs of a particular situation. Suitable sterilization techniques are known and will be chosen by those skilled in the art depending on the needs of a particular situation or to accommodate the properties of a given substance. Sterilizing a device designed according to this invention can be completed before or after packaging.
• Variations of the filling steps are within the scope of this invention. For example, the stopper can be inserted first, then fill the syringe, followed by applying a tip cap.[0046]
• The actual insertion of the desired substance can be accomplished in any of several known manners. Example filling techniques are disclosed in U.S. Pat. No. 5,620,425 to Hefferman et al.; U.S. Pat. No. 5,597,530 to Smith et al.; U.S. Pat. No. 5,537,042 to DeHaen; U.S. Pat. No. 5,531,255 to Vacca; U.S. Pat. No. 5,519,984 to Veussink et al.; U.S. Pat. No. 5,373,684 to Veussink et al.; U.S. Pat. No. 5,265,154 to Liebert et al.; U.S. Pat. No. 5,287,983 to Liebert et al.; and U.S. Pat. No. 4,718,463 to Jurgens, Jr. et al., each of which is incorporated by reference into this specification.[0047]
• The description just given is exemplary rather than limiting in nature. Variations and modifications may become apparent to those skilled in the art that do no necessarily depart from the basis of this invention. The scope of legal protection given to this invention can only be determined by studying the following claims.[0048]

Claims (24)

What is claimed is:

1. A nasal spray nozzle for use with a drug container such as a syringe for delivering liquid substances such as drugs, vaccines and the like into a nasal passage, comprising:

a rigid cap having a spray aperture at one end for delivering the substance to the nasal passage and an opening at a second end that is able to be selectively attached to a syringe containing the substance, the cap including an internal surface that defines a conduit between the opening and the spray aperture to allow the substance to flow toward the spray aperture; and

an internal valve supported within the conduit between the spray aperture and the opening, the valve only allowing the substance to flow through the spray aperture under pressure such that a spray mist of substance is delivered from the spray aperture.

2. The spray nozzle as recited inclaim 1 wherein the valve includes a generally flexible member supported within the cap that is biased into engagement with the internal surface of the cap such that only pressurized substance flows past the flexible member and toward the spray aperture in a single direction.

3. The spray nozzle as recited inclaim 1, wherein the valve is integrally formed within the cap and includes a flexible member that is biased to close off the conduit such that only pressurized substance flows past the flexible member in a single direction toward the spray aperture.

4. The spray nozzle as recited inclaim 1 wherein the cap is made from a rigid plastic material and includes a structure adjacent the opening that facilitates attaching the cap to the syringe and precludes subsequent removal of the cap.

5. The spray nozzle as recited inclaim 1 including a flange extending radially outward from the cap near the opening for preventing over-insertion of the cap into the nasal passage.

6. The spray nozzle as recited inclaim 1 wherein the cap includes a generally elongated body portion that extends from the opening in a direction opposite from the conduit, the body portion having a sidewall that is adapted to be received over an elongate syringe body and including a flange at a terminal end of the body portion that is adapted to accommodate a finger of a user to facilitate grasping the cap and delivering the substance from the syringe to the nasal passage.

7. The spray nozzle as recited inclaim 6, wherein the elongate body portion is generally cylindrical and the sidewall is continuous.

8. The spray nozzle as recited inclaim 6, wherein the elongate body portion has two generally arcuate sidewall portions that are spaced apart from each other, each sidewall portion having a flange at the terminal end.

9. The spray nozzle ofclaim 6, including an extended external surface on the cap near the opening that prevents over insertion of the cap into the nasal passage, the extended external surface having an outside dimension that is smaller than an outside dimension of the flange.

10. A nasal delivery device for delivering liquid substances such as drugs, vaccines and the like to a nasal passage, comprising:

a syringe having a body with an outlet opening at one end; and

a spray nozzle including

a separate, generally rigid cap having an internal surface that is selectively sealingly secured to the syringe body adjacent the outlet opening, the cap including an internal surface that defines a conduit in fluid communication with the outlet opening, the cap including a spray aperture at a distal end for delivering the liquid substance to the nasal passage; and

a valve supported by the cap between the spray aperture and the outlet opening that allows only pressurized substance to flow through the conduit and the spray aperture while also preventing unpressurized substance from flowing through the spray aperture.

11. The device ofclaim 10, wherein the syringe body includes a luer tip near the outlet opening and the cap includes cooperating structure for engaging the luer tip of the syringe.

12. The device ofclaim 10, wherein the syringe includes a groove formed on an exterior surface near the outlet opening and the cap includes a corresponding projection on the internal surface that is at least partially received by the groove.

13. The device ofclaim 12, wherein the projection is sufficiently rigid such that the cap is fixedly secured to the syringe when the projection is received by the groove precluding subsequent removal of the spray nozzle.

14. The device ofclaim 10, wherein the cap includes a radially outward projecting flange for preventing over-insertion of the nozzle into the nasal passage.

15. The device ofclaim 10, wherein the syringe includes an elongate barrel that defines a chamber for containing the substance prior to delivery of the liquid and a plunger rod for pushing the liquid out of the barrel, and wherein the cap includes a generally elongated body portion having a sidewall that is received over the syringe barrel and includes a flange at a terminal end of the body portion that is adapted to accommodate a finger of a user to facilitate grasping the cap and pushing the plunger rod to deliver the substance from the syringe to the nasal passage.

16. The device ofclaim 15, wherein the elongate body portion is generally cylindrical and the sidewall is continuous.

17. The device ofclaim 15, wherein the elongate body portion has two generally arcuate sidewall portions that are spaced apart from each other, each sidewall portion having a flange at the terminal end.

18. The device ofclaim 15, including an extended external surface on the cap near the opening that prevents over-insertion of the cap into the nasal passage, the extended external surface having an outside dimension that is smaller than an outside dimension of the flange.

19. The device ofclaim 15, including a dosage limiter that permits a selected amount of the substance to be delivered through the spray aperture, the dosage limiter limiting a range of motion of the plunger rod relative to the barrel.

20. The device ofclaim 19, wherein the dosage limiter is selectively placed in a first position relative to the barrel and the plunger to permit approximately one half of the substance to be delivered through the spray aperture and then selectively removed such that a second half of the substance can be subsequently delivered through the spray aperture.

21. The device ofclaim 10, wherein the syringe includes an elongate barrel that defines a chamber and said chamber prefilled with at least one substance to be nasally delivered such as a drug, vaccine and the like.

22. A method of intranasally delivering at least one substance such as a drug, vaccine and the like into a nasal passage, comprising the steps of:

attaching a nasal spray nozzle to a drug container such as a syringe, with said nasal spray nozzle including a rigid cap having a spray aperture at one end for delivering the substance to the nasal passage and an opening at a second end that is able to be selectively attached to the syringe containing the substance to be delivered, the cap including an internal surface that defines a conduit between the opening and the spray aperture to allow the substance to flow toward the spray aperture, and an internal valve supported within the conduit between the spray aperture and the opening, the valve only allowing the substance to flow through the spray aperture under pressure such that a spray mist of the substance may be delivered from the spray aperture;

inserting at least a portion of the nasal spray nozzle with the syringe attached thereto into one nostril of a person to whom the substance is to be intranasally delivered, said syringe including a plunger rod;

applying pressure on the plunger rod in a distal direction to cause a predetermined amount of the substance to flow through a passageway into the conduit of the cap such that a spray mist of the substance is delivered from the spray aperture into the nostril of the person; and

removing the nasal sprayer nozzle from said nostril.

23. The method ofclaim 22, further comprising the steps of:

removing a limiter from the plunger rod;

inserting at least a portion of the nasal spray nozzle with the syringe attached thereto into another nostril of the person to whom the substance is to be intranasally delivered;

applying pressure on the plunger rod in a distal direction to cause a predetermined amount of the substance to flow through a passageway into the conduit of the cap such that a spray mist of the substance is delivered from the spray aperture into the other nostril of the person; and

removing the nasal sprayer nozzle from said other nostril.

24. The method described inclaim 22 wherein said predetermined amount of the substance delivered into the nostril of the person is substantially equal to about half the amount of the substance contained in the syringe.

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