Immune modulation using peptides and other compositions

• US 9,393,264 B2
• Filed: 12/04/2013
• Issued: 07/19/2016
• Est. Priority Date: 03/13/2013
• Status: Active Grant

• Current Assignee: Transdermal Biotechnology, Inc.
• Original Assignee: Transdermal Biotechnology, Inc.
• Inventors: Perricone, Nicholas V.
• Primary Examiner(s): Maewall, Snigdha
• Application Number:
  US14/096,054
• Publication Number:
  US 20140271730A1
• Time in Patent Office: 958 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/34 Melanocyte stimulating hormone [MSH], e.g. alpha- or beta-melanotropin
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/186 Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/548 Phosphates or phosphonates, e.g. bone-seeking phospholipids A61K47/544
• 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: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection

Abstract

The present invention generally relates to compositions and methods for topical or transdermal delivery for immune modulation. In some cases, the composition may include nitric oxide and/or peptides such as thyrotropin-releasing hormone (TRH) and/or GnRH (gonadotropin-releasing hormone). The nitric oxide and/or peptide may be present within a first phase comprising a lecithin, such as phosphatidylcholine. In certain embodiments, the lecithin is present in liposomes, micelles, or other structures containing nitric oxide, peptides, or both. The composition can take the form of a gel, a cream, a lotion, an ointment, a solution, a solid “stick,” etc., that can be rubbed or sprayed onto the skin. Other aspects of the present invention are generally directed to methods of making or using such compositions, methods of promoting such compositions, kits including such compositions, or the like.

Claims

1. A method, comprising:

administering, to the skin of a subject to modulate the immune system of the subject, a composition comprising an effective amount of thyrotropin-releasing hormone (TRH) and molecular nitric oxide to modulate the immune system, and a carrier having a phosphatidylcholine component entrapping the nitric oxide, wherein the composition is stable at room temperature.

2. The method of claim 1, wherein the composition further comprises melanocyte-stimulating hormone (MSH).

3. The method of claim 1, wherein the composition further comprises the amino acid sequence KPV.

4. The method of claim 2, wherein the composition further comprises an effective amount of MSH.

5. The method of claim 3, wherein the composition further comprises an effective amount of a peptide comprising the amino acid sequence KPV.

6. The method of claim 1, wherein the molecular nitric oxide is present within the carrier as a gas or bound by hydrogen bonds or van der Waals forces.

7. The method of claim 1, wherein the phosphatidylcholine carrier stabilizes the nitric oxide at a temperature at or lower than 80°

C.

8. A method, comprising contacting the skin of a subject to modulate the immune system of the subject with a composition comprising:

an emulsion comprising a first phase comprising thyrotropin-releasing hormone (TRH), molecular nitric oxide, and lecithin, and a second phase comprising an emulsifier, wherein the lecithin is present at least about 0.25% by weight of the composition, and wherein the first phase comprises no more than about 250 ppm of water by weight of the composition.

9. The method of claim 8, wherein the composition further comprises melanocyte-stimulating hormone (MSH).

10. The method of claim 8, wherein the composition further comprises a peptide comprising the amino acid sequence KPV.

11. The method of claim 9, wherein the composition further comprises an effective amount of MSH.

12. The method of claim 10, wherein the composition further comprises an effective amount of a peptide comprising the amino acid sequence KPV.

13. The method of claim 8, wherein the molecular nitric oxide is present within the emulsion as a gas or bound by hydrogen bonds or van der Waals forces to the lecithin.

14. The method of claim 8, wherein at least some of the nitric oxide is present within the first phase bound to phosphatidylcholine.

15. The method of claim 8, wherein the lecithin comprises a phosphatidylcholine, and wherein at least some of the phosphatidylcholine comprises a polyenylphosphatidylcholine.

16. A method, comprising:

administering, topically to the skin of a subject, a composition comprising an effective amount of thyrotropin-releasing hormone (TRH), molecular nitric oxide, and phosphatidylcholine to modulate the immune system of the subject, wherein the composition is a cream, a gel, a lotion, or an ointment, and wherein the composition comprises no more than about 250 ppm of water by weight of the composition.

17. The method of claim 16, wherein the composition comprises a liquid crystal structure comprising the phosphatidylcholine.

18. The method of claim 17, wherein at least a portion of the liquid crystal structure is multilamellar.

19. The method of claim 16, wherein at least some of the phosphatidylcholine comprises a polyenylphosphatidylcholine.