Cardiovascular disease treatment and prevention

• US 9,827,316 B2
• Filed: 01/19/2017
• Issued: 11/28/2017
• 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:
  US15/409,857
• Publication Number:
  US 20170196981A1
• Time in Patent Office: 313 Days
• 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 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 38/066 TRH, thyroliberin, thyrotropin releasing hormone
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• 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 38/43 Enzymes; Proenzymes; Derivatives thereof
• CPC Class Codes: A61K 38/55 Protease inhibitors
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• 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 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The present invention generally relates to compositions and methods for treatment of subjects having or at risk of arteriosclerosis, hypertension, sickle-cell anemia, or other conditions. In some cases, the composition may include nitric oxide, peptides, or both. 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 and/or peptides such as thyrotropin-releasing hormone (TRH) and/or GnRH (gonadotropin-releasing hormone). 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 having or at risk of atherosclerosis, a composition comprising an effective amount of gonadotropin-releasing hormone (GnRH) and molecular nitric oxide to treat or prevent atherosclerosis, and a carrier comprising lecithin containing the molecular nitric oxide, wherein the composition comprises no more than about 250 ppm of water by weight of the composition.

2. The method of claim 1, wherein the carrier further comprises polyenylphosphatidylcholine.

3. The method of claim 1, wherein the composition comprises a liquid crystal structure.

4. The method of claim 1, wherein the composition is stable at room temperature.

5. The method of claim 1, wherein the lecithin is present at at least about 0.25% by weight of the composition.

6. The method of claim 1, wherein the molecular nitric oxide is present at at least about 0.5% by weight of the composition without nitric oxide.

7. The method of claim 1, wherein the molecular nitric oxide is present within the composition as a gas.

8. The method of claim 1, wherein the molecular nitric oxide is bound by hydrogen bonds or van der Waals forces to the lecithin.

9. The method of claim 1, wherein the composition is a cream.

10. A method, comprising:

administering, to the skin of a subject having or at risk of hypertension, a composition comprising an effective amount of gonadotropin-releasing hormone (GnRH) and molecular nitric oxide to treat or prevent hypertension, and a carrier comprising lecithin containing the molecular nitric oxide, wherein the composition comprises no more than about 250 ppm of water by weight of the composition.

11. The method of claim 10, wherein the carrier further comprises polyenylphosphatidylcholine.

12. The method of claim 10, wherein the composition comprises a liquid crystal structure.

13. The method of claim 10, wherein the composition is stable at room temperature.

14. The method of claim 10, wherein the lecithin is present at at least about 0.25% by weight of the composition.

15. The method of claim 10, wherein the molecular nitric oxide is present at at least about 0.5% by weight of the composition without nitric oxide.

16. The method of claim 10, wherein the molecular nitric oxide is present within the composition as a gas.

17. The method of claim 10, wherein the molecular nitric oxide is bound by hydrogen bonds or van der Waals forces to the lecithin.

18. The method of claim 10, wherein the composition is a cream.

19. The method of claim 10, wherein the composition is a gel.

20. A method, comprising:

administering, to the skin of a subject having or at risk of a cardiovascular disease, a composition comprising an effective amount of gonadotropin-releasing hormone (GnRH) and molecular nitric oxide to treat or prevent the cardiovascular disease, and a carrier comprising lecithin containing the molecular nitric oxide, wherein the composition comprises no more than about 250 ppm of water by weight of the composition.

21. The method of claim 20, wherein the carrier further comprises polyenylphosphatidylcholine.

22. The method of claim 20, wherein the composition comprises a liquid crystal structure.

23. The method of claim 20, wherein the composition is stable at room temperature.

24. The method of claim 20, wherein the lecithin is present at at least about 0.25% by weight of the composition.

25. The method of claim 20, wherein the molecular nitric oxide is present at at least about 0.5% by weight of the composition without nitric oxide.

26. The method of claim 20, wherein the molecular nitric oxide is present within the composition as a gas.

27. The method of claim 20, wherein the molecular nitric oxide is bound by hydrogen bonds or van der Waals forces to the lecithin.

28. The method of claim 20, wherein the composition is a cream.