Transdermal delivery system for dried particulate or lyophilized medications

• US 7,383,084 B2
• Filed: 03/27/2006
• Issued: 06/03/2008
• Est. Priority Date: 10/31/2002
• Status: Expired due to Fees

• Current Assignee: Syneron Medical Limited (Syneron Incorporated)
• Original Assignee: TransPharma Medical Ltd. (Syneron Incorporated)
• Inventors: Stern, Meir, Levin, Galit
• Primary Examiner(s): Monshipouri; Maryam
• Assistant Examiner(s): Tsay; Marsha M
• Application Number:
  US11/390,844
• Publication Number:
  US 20060233871A1
• Time in Patent Office: 799 Days
• Field of Search: 424/449, 424/447, 604/20, 530/303, 600/372
• US Class Current: 604/20
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61K 9/703 characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61N 1/042 Material of the electrode
• CPC Class Codes: A61N 1/0436 Material of the electrode
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

The present invention provides a system for transdermal delivery of dried or lyophilized pharmaceutical compositions and methods using thereof. The system comprises an apparatus for facilitating transdermal delivery of an agent that generates hydrophilic micro-channels, and a patch comprising a therapeutically active agent. The present invention is useful for transdermal delivery of hydrophilic agents, particularly of high molecular weight proteins.

Claims

1. A printed patch comprising a non-adhesive liner and a dried pharmaceutical composition comprising parathyroid hormone (PTH) or a fragment thereof that can elevate calcium ions or decrease phosphorus in blood in a manner similar to that of PTH(1-34), with the PTH or fragment being present on the non-adhesive liner, wherein the non-adhesive liner is made of a material that is not permeable to PTH or the fragment thereof.

2. The printed patch according to claim 1, wherein PTH is human PTH (1-34) having the amino acid sequence from amino acid 1 to amino acid 34 of full length human PTH.

3. The printed patch according to claim 1, wherein the pharmaceutical composition further comprises a stabilizer.

4. The printed patch according to claim 3, wherein the stabilizer is a simple or complex carbohydrate.

5. The printed patch according to claim 4, wherein the simple or complex carbohydrate is selected from the group consisting of mannose, glucose, galactose, raffinose, cellobiose, gentiobiose, sucrose and trehalose.

6. The printed patch according to claim 1, wherein the pharmaceutical composition further comprises an acid to yield a pH in the range from about 3 to about 6 in solution before drying.

7. The printed patch according to claim 6, wherein the pharmaceutical composition comprises hPTH (1-34), sucrose, and acetic acid to yield a pH of about 4.0 in solution before drying.

8. The printed patch according to claim 6, wherein the pharmaceutical composition comprises hPTH (1-34), trehalose, and citric acid to yield a pH of about 4.0 in solution before drying.

9. The printed patch according to claim 6, wherein the pharmaceutical composition comprises hPTH (1-34), trehalose, and acetic acid to yield a pH of about 4.0 in solution before drying.

10. The printed patch according to claim 1, wherein the pharmaceutical composition further comprises a buffering agent.

11. The printed patch according to claim 10, wherein the pharmaceutical composition comprises hPTH (1-34), trehalose, and acetate buffer to yield a pH of about 4.0 in solution before drying.

12. The printed patch of claim 1 wherein the fragment is selected from the group consisting of PTH (1-34) having the amino acid sequence from amino acid 1 to amino acid 34 of full length PTH, PTH (1-37), PTH (1-38), or PTH (1-41).

13. A system for transdermal delivery of parathyroid hormone (PTH) or a fragment thereof from a dried pharmaceutical composition comprising:

an apparatus for facilitating transdermal delivery of PTH or a fragment thereof through skin of a subject, the apparatus capable of generating a plurality of micro-channels in an area on the skin of the subject, and a patch according to claim 1.

14. The system according to claim 13, wherein the apparatus comprising:

a. an electrode cartridge, optionally removable, comprising a plurality of electrodes; and

b. a main unit comprising a control unit which is adapted to apply electrical energy to the plurality of electrodes when the plurality of electrodes are in vicinity of the skin enabling ablation of stratum corneum in an area beneath said plurality of electrodes, thereby generating a plurality of micro-channels.

15. The system according to claim 14, wherein the electrical energy is at radio frequency.

16. A method for transdermal administration of a dried pharmaceutical composition comprising parathyroid hormone (PTH) or a fragment thereof that can elevate calcium ions or decrease phosphorus in blood in a manner similar to that of PTH (1-34), the method comprising:

(a) generating a plurality of micro-channels in an area of the skin of a subject;

(b) affixing a printed patch according to claim 10 to the area of the skin of the subject; and

(c) achieving dose efficiency of at least 10%.

17. The method of claim 16, wherein PTH is human PTH (1-34) having the amino acid sequence from amino acid 1 to amino acid 34 of full length human PTH.

18. The method of claim 16, wherein the subject is human.

19. The method of claim 16, wherein the pharmaceutical composition further comprises a stabilizer.

20. The method according to claim 19, wherein the stabilizer is a simple or complex carbohydrate.

21. The method according to claim 20, wherein the simple or complex carbohydrate is selected from the group consisting of mannose, glucose, galactose, raffinose, cellobiose, gentiobiose, sucrose and trehalose.

22. The method according to claim 16, wherein the pharmaceutical composition further comprises an acid to yield a pH in the range from about 3 to about 6 in solution before drying.

23. The method according to claim 22, wherein the pharmaceutical composition comprises hPTH (1-34), sucrose, and acetic acid to yield a pH of about 4.0 in solution before drying.

24. The method according to claim 22, wherein the pharmaceutical composition comprises hPTH (1-34), trehalose, and citric acid to yield a pH of about 4.0 in solution before drying.

25. The method according to claim 22, wherein the pharmaceutical composition comprises hPTH (1-34), trehalose, and acetic acid to yield a pH of about 4.0 in solution before drying.

26. The method according to claim 16, wherein the pharmaceutical composition further comprises a buffering agent.

27. The method according to claim 26, wherein the pharmaceutical composition comprises hPTH (1-34), trehalose, and acetate buffer to yield a pH of about 4.0 in solution before drying.

28. The method of claim 16 wherein the fragment is selected from the group consisting of PTH (1-34) having the amino acid sequence from amino acid 1 to amino acid 34 of full length PTH, PTH (1-37), PTH (1-38), or PTH (1-41).