Transepithelial delivery of peptides with incretin hormone activities

• US 7,442,682 B2
• Filed: 09/02/2005
• Issued: 10/28/2008
• Est. Priority Date: 10/19/2004
• Status: Expired due to Fees

• Current Assignee: Nitto Denko Corporation
• Original Assignee: Nitto Denko Corporation
• Inventors: Yu, Lei, Liu, Jian, Kitaura, Chieko, Minomi, Kenjiro, Okubo, Katsuyuki, Hou, Zheng, Kagehisa, Natsuko, Okada, Keisaku, Song, Yucheng, Kamiyama, Masashi
• Primary Examiner(s): Gupta; Anish
• Assistant Examiner(s): Ha; Julie
• Application Number:
  US11/219,145
• Publication Number:
  US 20060084604A1
• Time in Patent Office: 1,152 Days
• Field of Search: None
• US Class Current: 514/1.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/62 the modifying agent being a protein, peptide or polyamino acid
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/57563 Vasoactive intestinal peptide [VIP]; Related peptides
• CPC Class Codes: C07K 14/605 Glucagons

Abstract

Compositions and methods are disclosed for the treatment of diabetes and related diseases using peptides with incretin hormone activity. Preferably, the peptide with incretin hormone activity is GLP-1, exendin or an analog of GLP-1 or exendin. The peptides with incretin hormone activity are administered transepithelially using a transepithelial carrier peptide. The transepithelial peptide contains sufficient amino, guanidine or amidino groups to stimulate transepithelial delivery. In some embodiments, the transepithelial carrier and the peptide with incretin hormone activity are embedded in a pressure sensitive adhesive layer of a plaster or patch.

Claims

1. A topical preparation for the treatment of diabetes comprising:

a conjugate comprising a peptide with incretin hormone activity covalently attached to a transepithelial carrier; and

a skin contact base,

wherein the conjugate has a concentration in the skin contact base from 0.001% to 70%,

wherein the peptide with incretin hormone activity is SEQ ID NO;

6 or SEQ ID NO;

33 optionally having a cysteine amino acid residue attached to the N-terminus or the C-terminus of the peptide with incretin activity, or having a cysteine amino acid residue which replaces one of the serine amino acid residues in the peptide with incretin activity, and

wherein the transepithelial carrier comprises SEQ ID NO;

32.

2. The topical preparation of claim 1, wherein the topical preparation is a conjugate selected from the group consisting of structures (V) and (VI) as follows:

3. The topical preparation of claim 2, wherein structures V and VI are capable of degradation by hydrolysis or glutathione-assisted reduction to release the peptide with incretin hormone activity in its bioactive form.

4. The topical preparation of claim 1, wherein at least one amino acid in the transepithelial carrier is a D-amino acid.

5. The topical preparation of claim 1, wherein all of the amino acids in the transepithelial carrier are D-amino acids.

6. The topical preparation of claim 1, wherein the peptide with incretin activity comprises at least one cysteine amino acid residue, wherein the at least one cysteine is introduced by addition or replacement.

7. The topical preparation of claim 6, wherein at least one amino acid in the transepithelial carrier is a D-amino acid.

8. The topical preparation of claim 6, wherein all of the amino acids in the transepithelial carrier are D-amino acids.

9. The topical preparation of claim 1 wherein the peptide with incretin hormone activity is targeting glucagon-like peptide-1 receptors and glucose-dependent insulinotropic polypeptide receptors.

10. The topical preparation of claim 1, wherein the skin contact base is selected from the group consisting of an ointment, a gel, an emulsion, a suspension, a cataplasm, a plaster, a lotion and a liniment.

11. The topical preparation of claim 1, wherein the skin contact base is a plaster, comprising a pressure sensitive adhesive and a backing.

12. The topical preparation of claim 11, further comprising water or an organic liquid ingredient, which is added to the pressure sensitive adhesive layer.

13. The topical preparation of claim 12, wherein the organic liquid ingredient is selected from the group consisting of glycol, olive oil, castor oil, squalane, orange oil, mineral oil, C_6-20 fatty acid, C_6-20 fatty acid ester and C_1-20 alcohol.

14. The topical preparation of claim 1, wherein the skin contact base provides sustained release.

15. The topical preparation of claim 1, wherein the epithelial tissue is skin tissue.

16. A method of treating type 2 diabetes in a human subject in need thereof, comprising administering the topical preparation of claim 1 to the human subject.

17. A method for treating type 2 diabetes in a human subject in need thereof, the method comprising:

providing a topical preparation comprising a peptide with incretin hormone activity and a transepithelial carrier according to claim 1;

placing said topical preparation in contact with the skin of a patient such that said active agent is released topically onto said skin of said patient such that said peptide with incretin hormone activity is released onto said skin of said patient; and

delivering an effective dose of the peptide with incretin hormone activity to stimulate the secretion of insulin in vivo in the human subject in need thereof, without inducing serious nausea and/or vomiting.

18. The method of claim 17 wherein the peptide with incretin hormone activity is targeting glucagon-like peptide-1 receptors and glucose-dependent insulinotropic polypeptide receptors.

19. A topical preparation for the treatment of diabetes comprising:

a peptide comprising SEQ ID NO;

45; and

a skin contact base,

wherein the peptide has a concentration in the skin contact base from 0.001% to 70%.

20. The topical preparation of claim 19, wherein at least one amino acid in the peptide is a D-amino acid.

21. The topical preparation of claim 19, wherein all of the amino acids in the peptide are D-amino acids.

22. The topical preparation of claim 19, wherein the skin contact base is selected from the group consisting of an ointment, a gel, an emulsion, a suspension, a cataplasm, a plaster, a lotion and a liniment.

23. The topical preparation of claim 19, wherein the skin contact base is a plaster, comprising a pressure sensitive adhesive and a backing.

24. The topical preparation of claim 23, further comprising water or an organic liquid ingredient, which is added to the pressure sensitive adhesive layer.

25. The topical preparation of claim 24, wherein the organic liquid ingredient is selected from the group consisting of glycol, olive oil, castor oil, squalane, orange oil, mineral oil, C_6-20 fatty acid, C_6-20 fatty acid ester and C_1-20 alcohol.

26. The topical preparation of claim 19, wherein the skin contact base provides sustained release.

27. The topical preparation of claim 19, wherein the epithelial tissue is skin tissue.

28. A method of treating type 2 diabetes in a human subject in need thereof, comprising administering the topical preparation of claim 19 to the human subject.

29. A method for treating type 2 diabetes in a human subject in need thereof, the method comprising:

providing a topical preparation comprising a peptide with incretin hormone activity and a transepithelial carrier according to claim 19;

placing said topical preparation in contact with the skin of a patient such that said peptide with incretin hormone activity is released topically onto said skin of said patient; and

delivering an effective dose of the peptide with incretin hormone activity to stimulate the secretion of insulin in vivo in the human subject in need thereof, without inducing serious nausea and/or vomiting.