Trans-mucosal particle delivery

• US 6,010,478 A
• Filed: 08/14/1997
• Issued: 01/04/2000
• Est. Priority Date: 02/14/1995
• Status: Expired due to Fees

• Current Assignee: Powderject Research Limited (Pfizer Inc.)
• Original Assignee: Powderject Research Limited (Pfizer Inc.)
• Inventors: Bell, John, Sarphie, David Francis, Greenford, John Christopher, Bellhouse, Brian John
• Primary Examiner(s): McDermott, Corrine
• Assistant Examiner(s): GRING, NOELLE K
• Application Number:
  US08/919,184
• Time in Patent Office: 873 Days
• Field of Search: 604/68, 604/70, 604/72, 604/131, 604/130, 604/140, 604/141, 604/143, 604/146, 222/631, 222/389
• US Class Current: 604/70
• CPC Class Codes: A61M 5/2053 Media being expelled from injector by pressurised fluid or vacuum for infusion A61M5/145, A61M5/155
• CPC Class Codes: A61M 5/3015 for injecting a dose of particles in form of powdered drug, e.g. mounted on a rupturable membrane and accelerated by a gaseous shock wave or supersonic gas flow cell injection devices C12M3/006

Abstract

A needleless syringe capable of accelerating particles comprising a therapeutic agent across skin or mucosal tissue of a vertebrate subject is provided. The syringe comprises an elongate tubular nozzle having a bend along its length and is connected to or capable of connection to a suitable energizing means for producing in the nozzle a supersonic condition sufficient to cause delivery of the particles to a target surface. A method for delivering particles comprising a therapeutic agent from the needleless syringe is also provided.

Claims

1. A needleless syringe for delivering particles comprising a therapeutic agent across skin or mucosal tissue of a vertebrate subject, said syringe comprising:

(a) an elongate tubular nozzle having an upstream terminus and a downstream terminus and a bend between said upstream and downstream termini, wherein the upstream terminus is capable of interfacing with an energizing means; and

(b) release means associated with the nozzle for releasing into the upstream terminus of the nozzle an energetic force from the energizing means to create a supersonic condition within the nozzle.

2. The syringe of claim 1, wherein the upstream terminus of the nozzle is interfaced with a source of pressurized gas.

3. The syringe of claim 2, wherein the source of pressurized gas comprises a gas canister containing a releasable volume of a driving gas.

4. The syringe of claim 2, wherein the source of pressurized gas contains a gas which is lighter than air.

5. The syringe of claim 4, wherein the nozzle contains a volume of gas that is lighter than air.

6. The syringe of claim 2 further comprising valve means capable of actuation to release a volume of gas from the source of pressurized gas to create a gaseous shock wave within the nozzle.

7. The syringe of claim 6, wherein the release means comprises a rupturable membrane arranged within and closing the nozzle, whereby the released gas is temporarily retained in a chamber behind said membrane prior to the rupture thereof.

8. The syringe of claim 1, wherein the release means is a self-opening valve.

9. The syringe of claim 1, wherein the nozzle contains a volume of gas that is lighter than air.

10. The syringe of claim 1, wherein the supersonic condition within the nozzle is a supersonic gas flow.

11. The syringe of claim 10, wherein the nozzle diameter between the bend and the downstream terminus is smaller than the nozzle diameter between the upstream terminus and the bend, whereby the supersonic gas flow is attained in the nozzle only between the bend and the downstream terminus.

12. The syringe of claim 11, wherein the portion of the nozzle between the bend and the downstream terminus has a convergent portion.

13. The syringe of claim 1 further comprising an upstream and a downstream rupturable membrane that extend across the interior of the nozzle, wherein particles comprising a therapeutic agent are housed in the nozzle between said rupturable membranes.

14. The syringe of claim 13, wherein the release means comprises the upstream or downstream rupturable membrane.

15. The syringe of claim 1 further comprising a diaphragm arranged adjacent to the downstream terminus of the nozzle, said diaphragm having an internal surface facing the interior of the nozzle and an external surface, wherein said diaphragm is moveable between an initial position in which a concavity is provided on the external surface of the diaphragm, and a dynamic position in which the external surface of the diaphragm is substantially convex.

16. The syringe of claim 15, wherein the diaphragm is an eversible dome-shaped membrane comprised of a flexible polymeric material.

17. The syringe of claim 15, wherein the diaphragm is a bistable membrane that is moveable between an initial inverted position and a dynamic everted position.

18. The syringe of claim 15 further comprising particles comprising a therapeutic agent housed within the concavity in the external surface of the diaphragm.

19. The syringe of claim 1, wherein the nozzle is flexible such that the bend in the nozzle can be adjusted over a range of angles.

20. A method for delivering particles comprising a therapeutic agent to skin or mucosal tissue, said method comprising:

(a) providing the needleless syringe of claim 1 interfaced with an energizing means;

(b) loading said needleless syringe with particles comprising a therapeutic agent;

(c) positioning the downstream terminus of the nozzle of said syringe adjacent to the skin or mucosal tissue; and

(d) actuating the release means to create a supersonic condition within the nozzle, thereby accelerating said particles into the skin or mucosal tissue.

21. The method of claim 20, wherein the particles are accelerated toward the skin or mucosal tissue at a velocity of about 200 to 2,500 m/sec.

22. The method of claim 20, wherein the particles have a size predominantly in the range of about 10 to 40 μ

m.

23. The method of claim 20, wherein the particles have a density in the range of 0.5 to 2 g/cm³.

24. The method of claim 20, wherein the particles are accelerated from the downstream terminus of the nozzle at a momentum density between 4 and 7 kg/sec/m.

25. The method of claim 20, wherein the therapeutic agent is a topically active local anaesthetic.

26. The method of claim 25, wherein the local anaesthetic is selected from the group consisting of lignocaine hydrochloride, lignocaine base, ropivacaine hydrochloride, bupivacaine, procaine, prilocaine, tetracaine, etidocaine, and benzocaine.

27. The method of claim 25, wherein the local anaesthetic is mixed with epinephrine.

28. The method of claim 20, wherein the therapeutic agent is selected from the group consisting of a systemically-active organic small molecule, an inorganic small molecule, a peptide, a protein, a vaccine, an oligonucleotide, and a metal ion.

29. The method of claim 28, wherein the therapeutic agent is selected from the group consisting of insulin, testosterone, growth hormone, glucagon, atropine, alprazolam, calcitonin, desmopressin, 5HT, dihydroergotamine, and interleukin.

30. The method of claim 20, wherein the particles are delivered to a mucosal surface.

31. The method of claim 30, wherein the particles are delivered to a mucosal surface selected from the group consisting of gum mucosa, cheek mucosa, palate mucosa, vaginal mucosa, rectal mucosa, nasal mucosa, and ocular mucosa.