Transdermal delivery system for dried particulate or lyophilized peptides and polypeptides

• US 7,662,404 B2
• Filed: 10/17/2006
• Issued: 02/16/2010
• Est. Priority Date: 10/31/2002
• Status: Active Grant

• Current Assignee: Syneron Medical Limited (Syneron Incorporated)
• Original Assignee: TransPharma Medical Ltd. (Syneron Incorporated)
• Inventors: Stern, Meir, Levin, Galit
• Primary Examiner(s): Nashed; Nashaat T
• Assistant Examiner(s): Tsay; Marsha M
• Application Number:
  US11/582,920
• Publication Number:
  US 20070082040A1
• Time in Patent Office: 1,218 Days
• Field of Search: None
• US Class Current: 424/447
• 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: 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 a peptide or polypeptide that generates hydrophilic micro-channels, and a patch comprising dried therapeutically peptide or polypeptide. Particularly, the system of the present invention facilitates transdermal delivery of parathyroid hormone useful for preventing or treating bone disorders.

Claims

1. A method for treating a bone disorder or disease comprising:

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

(b) affixing a printed patch to the area of the skin of the subject, the printed patch comprising a non-adhesive liner and a dried pharmaceutical composition comprising a therapeutically effective amount of a parathyroid hormone (PTH) or a fragment thereof that has PTH activity, and wherein the non-adhesive liner is made of a material that is not permeable to the PTH, and thereby treating the bone disorder or disease.

2. The method according to claim 1, wherein the PTH is a human PTH.

3. The method according to claim 2, wherein the human PTH is the fragment human PTH (1-34).

4. The method according to claim 1, wherein the pharmaceutical composition further comprises a stabilizer.

5. The method according to claim 4, wherein the stabilizer is a simple or complex carbohydrate.

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

7. The method according to claim 1, wherein the pharmaceutical composition further comprises an acidic component to yield a pH in the range from about 3 to about 6 in solution before drying.

8. The method according to claim 7, wherein the acidic component is selected from the group consisting of acetic acid, citric acid, and tartaric acid.

9. The method according to claim 8, wherein the pharmaceutical composition comprises hPTH (1-34), acetic acid, and trehalose at pH of about 4.0 in solution before drying.

10. The method according to claim 1, wherein the bone disorder or disease is selected from the group consisting of bone fractures, osteoporosis, arthritis, osteoarthritis, and glucocorticoid osteoporosis.

11. The method according to claim 1, wherein the subject is a human.

12. The method according to claim 1, wherein the subject is a woman.

13. The method according to claim 1, wherein the subject is a postmenopausal woman suffering from osteoporosis.

14. The method according to claim 1, wherein the pharmaceutical composition further comprising an antiresorptive agent.

15. The method according to claim 14, wherein the antiresorptive agent is selected from the group consisting of calcitonin, estrogen, bisphosphonates, fluoride, vitamin D, IGF-1, statins, and selective estrogen receptor modulators (SERMs).

16. The method according to claim 1, further comprising a step of administering a pharmaceutical composition comprising a therapeutically effective amount of an antiresorptive agent before, concurrently, or after affixing the patch.

17. The method according to claim 16, wherein the antiresorptive agent is selected from the group consisting of calcitonin, estrogen, bisphosphonates, fluoride, vitamin D, IGF-1, statins, and selective estrogen receptor modulators (SERMs).

18. The method according to claim 1, wherein the bone disorder is osteoporosis, and the pharmaceutical composition further comprises trehalose as a stabilizer, acetic acid in an amount sufficient to yield a pH in the range from about 3 to about 6 in solution before drying, and vitamin D as an antiresorptive agent.

19. The method according to claim 18, wherein the PTH peptide is human PTH (1-34) and the subject to be treated is a woman.

20. The method according to claim 1, wherein the bone disorder is osteoporosis, and the pharmaceutical composition further comprises trehalose as a stabilizer, and acetic acid in an amount sufficient to yield a pH in the range from about 3 to about 6 in solution before drying.