METHODS AND COMPOSITIONS FOR THE TREATMENT OF PROLIFERATIVE VASCULAR DISORDERS

• US 20130029950A1
• Filed: 07/26/2012
• Published: 01/31/2013
• Est. Priority Date: 07/26/2011
• Status: Active Grant

• Current Assignee: Children's Medical Center Corporation
• Original Assignee: Children's Medical Center Corporation
• Inventors: Bischoff, Joyce, Greenberger, Shoshana
• Granted Patent: US 9,220,716 B2
• Time in Patent Office: Days
• US Class Current: 514/171
• 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 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

The technology described herein is directed to methods and compositions for the treatment of proliferative vascular disorders, e.g. hemangioma. In some aspects, the methods and compositions described herein related to a mTOR inhibitor or nifedipine.

Claims

1. A method of treating a proliferative vascular disorder, the method comprising:

administering a mTOR inhibitor; and

administering a steroid or a beta-blocker or administering a steroid and a beta-blocker.

2. The method of claim 1, wherein the mTOR inhibitor is selected from the group consisting of:

everolimus;

temisrolimus; and

rapamycin.

3. The method of claim 1, wherein the steroid is a corticosteroid.

4. The method of claim 3, wherein the corticosteroid is selected from the group consisting of:

dexamethasone;

prednisone;

prednisolone;

triamcinolone;

clobetasol propionate;

betamethasone valerate;

betamethasone dipropionate; and

mometasone furoate.

5. The method of claim 1, wherein the beta-blocker is selected from the group consisting of:

atenolol;

nadolol;

propranolol and timolol.

6. The method of claim 1, wherein the i) mTOR inhibitor and ii) the steroid or beta-blocker are administered concomitantly.

7. The method of claim 1, wherein the proliferative vascular disorder is a vascular malformation.

8. The method of claim 1, wherein the proliferative vascular disorder is a vascular tumor.

9. The method of claim 1, wherein the proliferative vascular disorder is selected from the group consisting of:

hemangioma;

verrucous hemangioma;

nevoid hemangioma;

senile hemangioma;

kaposiform hemangioendothelioma;

pyogenic granuloma and congenital hemangioma.

10. The method of claim 1, wherein the proliferative vascular disorder is infantile hemangioma.

11. The method of claim 1, wherein one or more of the mTOR inhibitor, steroid, or beta-blocker are administered systemically.

12. The method of claim 1, wherein one or more of the mTOR inhibitor, steroid, or beta-blocker are administered orally.

13. The method of claim 1, wherein one or more of the mTOR inhibitor, steroid, or beta-blocker are administered intralesionally.

14. The method of claim 1, wherein one or more of the mTOR inhibitor, steroid, or beta-blocker are administered topically.

15. A pharmaceutical composition comprising i) a mTOR inhibitor and ii) a steroid or beta-blocker.

16. The composition of claim 15, further comprising a pharmaceutically acceptable carrier.

17. The composition of claim 15, wherein the mTOR inhibitor is selected from the group consisting of:

everolimus;

temisrolimus; and

rapamycin.

18. The composition of claim 15, wherein the steroid is a corticosteroid.

19. The composition of claim 18, wherein the corticosteroid is selected from the group consisting of:

dexamethasone;

prednisone;

prednisolone;

triamcinolone;

clobetasol propionate;

betamethasone valerate;

betamethasone dipropionate; and

mometasone furoate.

20. The composition of claim 15, wherein the beta-blocker is selected from the group consisting of:

atenolol;

nadolol;

propranolol and timolol.