Compositions and methods for treatment of edema

Patent metadata

Field	Value
Publication number	US-10251871-B2
Application number	US-201615549156-A
Country	US
Kind code	B2
Filing date	Feb 5, 2016
Priority date	Feb 5, 2015
Publication date	Apr 9, 2019
Grant date	Apr 9, 2019

Abstract

Provided are pharmaceutical compositions and methods of treating or preventing edema, using an anti-T cell agent, an anti-TGF-β1 agent, or an anti-angiotensin agent, preferably a combination of at least two such agents. The pharmaceutical compositions can be formulated for systemic or local administration, and are preferably administered topically.

First claim

The invention claimed is:

1. A pharmaceutical composition comprising:
(i) an effective amount of one or more anti-T cell agents; and
(ii) an effective amount of one or more anti-TGF-β1 agents and/or an effective amount of one or more anti-angiotensin agents;

wherein the composition is formulated for topical administration.

2. The pharmaceutical composition of claim 1 , wherein the anti-T cell agent is selected from the group consisting of tacrolimus, teriflunomide, leflunomide, cyclosporine, pimecrolimus, denileukin diftitox, and Basiliximab.

3. The pharmaceutical composition of claim 1 , wherein the anti-TGF-β1 agent is pirfenidone.

4. The pharmaceutical composition of claim 1 , wherein the anti-angiotensin agent is an angiotensin converting enzyme (ACE) inhibitor.

5. The pharmaceutical composition of claim 1 , wherein the anti-angiotensin agent is selected from the group consisting of captopril, zofenopril, enalapril, lisinopril, ramipril, quinapril, perindopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril, losartan, irbesartan, olmesartan, candesartan, telmisartan, valsartan, and fimasartan.

6. The pharmaceutical composition of any preceding claim 1 , comprising tacrolimus.

7. The pharmaceutical composition of claim 6 , comprising about 0.01% to about 1% tacrolimus.

8. The pharmaceutical composition of claim 3 , comprising about 0.1 mg/ml to about 5 mg/ml pirfenidone.

9. The pharmaceutical composition of claim 1 , comprising teriflunomide.

10. The pharmaceutical composition of claim 9 , comprising about 10 mg/ml to about 50 mg/ml teriflunomide.

11. The pharmaceutical composition of claim 1 , comprising leflunomide.

12. The pharmaceutical composition of claim 11 , comprising about 1% to about 20% leflunomide.

13. The pharmaceutical composition of claim 1 , comprising captopril.

14. The pharmaceutical composition of claim 13 , comprising about 1% to about 20% captopril.

15. The pharmaceutical composition of claim 1 , wherein the composition is in a form selected from an ointment, a cream, a lotion, a paste, a gel, a mousse, a foam, a lacquer, a suspension, a liquid, and a spray.

16. The pharmaceutical composition of claim 15 , wherein the composition is in the form of an ointment.

17. A method of treating edema, the method comprising administering to a subject in need thereof a pharmaceutical composition comprising an effective amount of one or more drugs selected from the group consisting of tacrolimus, teriflunomide, leflunomide, cyclosporine, pimecrolimus, denileukin diftitox, Basiliximab, pirfenidone, captopril, zofenopril, enalapril, lisinopril, ramipril, quinapril, perindopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril, losartan, irbesartan, olmesartan, candesartan, telmisartan, valsartan, and fimasartan.

18. The method of claim 17 , wherein the pharmaceutical composition comprises:
(i) an effective amount of one or more anti-T cell agents selected from the group consisting of tacrolimus, teriflunomide, leflunomide, cyclosporine, pimecrolimus, denileukin diftitox, and Basiliximab; and
(ii) an effective amount of one or more anti-TGF-β1 agents and/or anti-angiotensin agents selected from the group consisting of pirfenidone, captopril, zofenopril, enalapril, lisinopril, ramipril, quinapril, perindopril, benazepril, imidapril, trandolapril, cilazapril, fosinopril, losartan, irbesartan, olmesartan, candesartan, telmisartan, valsartan, and fimasartan.

19. The method of claim 17 , wherein the pharmaceutical composition comprises tacrolimus.

20. The method of claim 17 , wherein the pharmaceutical composition comprises pirfenidone.

21. The method of claim 17 , wherein the pharmaceutical composition comprises teriflunomide.

22. The method of claim 17 , wherein the pharmaceutical composition comprises leflunomide.

23. The method of claim 17 , wherein the pharmaceutical composition comprises captopril.

24. The method of claim 17 , wherein the pharmaceutical composition is administered topically.

25. The method of claim 24 , wherein the pharmaceutical composition is administered topically at least once a day.

26. The method of claim 17 , wherein the pharmaceutical composition is administered within about six weeks of a lymphatic injury.

Assignees

• Memorial Sloan Kettering Cancer Center

Inventors

• Mehrara Babak
• Gardenier Jason
• Savetsky Ira
• Aras Omer

Classifications

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/4418 Primary

  having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine · CPC title

• A61K31/277

  having a ring, e.g. verapamil · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title

• A61K9/06

  Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} · CPC title