Systems and methods for delivery of peptides

• US 9,295,647 B2
• Filed: 03/13/2013
• Issued: 03/29/2016
• 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:
  US13/801,402
• Publication Number:
  US 20140271808A1
• Time in Patent Office: 1,112 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 38/00 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 38/06 Tripeptides
• CPC Class Codes: A61K 38/066 TRH, thyroliberin, thyrotropin releasing hormone
• CPC Class Codes: A61K 38/095 Oxytocins; Vasopressins; Related peptides
• CPC Class Codes: A61K 38/2271 Neuropeptide Y
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/34 Melanocyte stimulating hormone [MSH], e.g. alpha- or beta-melanotropin
• CPC Class Codes: A61K 47/544 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 9/127 Liposomes

Abstract

The present invention generally relates to compositions and methods for topical or transdermal delivery. The compositions can be used in a variety of applications. In some cases, the composition may include nitric oxide and/or peptides. 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 vesicles 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. The composition can also be applied to a mucosal surface in some instances. 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 composition for transdermal delivery of a peptide and nitric oxide, comprising:

a phosphatidylcholine carrier entrapping molecular nitric oxide and comprising thyrotropin-releasing hormone (TRH), wherein the phosphatidylcholine carrier stabilizes the molecular nitric oxide at a temperature at or lower than 80°

C., wherein the molecular nitric oxide is present within the carrier as a gas or bound by hydrogen bonds or van der Waals forces, wherein the composition is stable at room temperature.

2. The composition of claim 1, wherein the composition comprises a liquid crystal structure comprising the phosphatidylcholine.

3. The composition of claim 2, wherein at least a portion of the liquid crystal structure is multilamellar.

4. A composition for transdermal delivery of a peptide and nitric oxide, 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 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, and 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.

5. The composition of claim 4, wherein the first phase forms discrete vesicles contained within the second phase.

6. The composition of claim 5, wherein the first phase forms liposomes contained within the second phase.

7. The composition of claim 6, wherein the first phase forms multilamellar liposomes contained within the second phase.

8. The composition of claim 4, wherein the first phase forms a liquid crystal.

9. The composition of claim 4, wherein the nitric oxide is present at at least about 0.5% by weight of the composition.

10. The composition of claim 4, wherein at least some of the nitric oxide is present within the first phase bound to phosphatidylcholine.

11. The composition of claim 4, wherein the lecithin comprises a phosphatidylcholine.

12. The composition of claim 11, wherein at least some of the phosphatidylcholine comprises a polyenylphosphatidylcholine.

13. The composition of claim 4, wherein the first phase comprises a fatty acid ester.

14. The composition of claim 4, wherein the first phase comprises ascorbate palmitate.

15. The composition of claim 4, wherein the first phase comprises isopropyl palmitate.

16. The composition of claim 4, wherein the composition is a gel.

17. The composition of claim 4, wherein the composition is a cream.

18. The composition of claim 4, wherein the composition is substantially transparent.