Stabilized steroid composition and method for its preparation

• US 20060205703A1
• Filed: 05/11/2006
• Published: 09/14/2006
• Est. Priority Date: 01/23/2003
• Status: Active Grant

• Current Assignee: PreCision Dermatology, Inc. (Bausch Health Cos., Inc.)
• Original Assignee: Triax Pharmaceuticals LLC (Bausch Health Cos., Inc.)
• Inventors: Patel, Pravin M.
• Granted Patent: US 7,981,877 B2
• Time in Patent Office: Days
• US Class Current: 514/171
• CPC Class Codes: A61K 31/202 having three or more double bonds, e.g. linolenic eicosanoids, e.g. leukotrienes A61K31/557
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• 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

Abstract

Stabilized, 17-substituted hydrocortisone containing compositions and methods of manufacture are disclosed. Isomerization of the hydrocortisone component of topical steroid compositions is markedly reduced by including an omega-6 acid component in the form of a free acid or as a compound such as an ester. Specifically disclosed are methods for preventing the isomerization of hydrocortisone 17-butyrate into hydrocortisone 21-butyrate through the use of safflower oil.

Claims

1. A method for stabilizing a composition including a 17-substituted hydrocortisone therein, said method comprising the step of:

adding a stabilizer to said composition, said stabilizer comprising an omega-6 acid or an ester of an omega-6 acid.

2. The method of claim 1, wherein said step of adding said stabilizer comprises adding linoleic acid to said composition.

3. The method of claim 1, wherein said step of adding said stabilizer to said composition comprises adding a triglyceride which includes an ester of said omega-6 acid to said composition.

4. The method of claim 3, wherein said triglyceride comprises safflower oil.

5. The method of claim 1, wherein the step of adding said stabilizer further comprises adding said stabilizer in an amount so that the omega-6 acid component thereof is at least equimolar to a quantity of said 17-substituted hydrocortisone.

6. The method of claim 5, wherein the molar amount of the omega-6 acid component is substantially greater than the molar amount of said 17-substituted hydrocortisone.

7. A method for inhibiting the isomerization of hydrocortisone 17-butyrate to hydrocortisone 21-butyrate, said method comprising the step of:

disposing said hydrocortisone 17-butyrate in a composition which includes a stabilizer comprising an omega-6 acid or an ester of an omega-6 acid.

8. The method of claim 7, wherein the stabilizer comprises linoleic acid.

9. The method of claim 7, wherein the stabilizer comprises a triglyceride which includes an ester of said omega-6 acid.

10. The method of claim 9, wherein said triglyceride comprises safflower oil.

11. The method of claim 7, wherein the step of adding said stabilizer further comprises adding said stabilizer in an amount so that the omega-6 acid component is at least equimolar to a quantity of said hydrocortisone 17-butyrate.

12. The method of claim 11, wherein the molar amount of the omega-6 acid component is substantially greater than the molar amount of hydrocortisone 17-butyrate.

14. The method of claim 11, wherein the stabilizer comprises safflower oil.

13. A method for stabilizing a 17-substituted hydrocortisone compound, said method comprising the step of:

disposing said hydrocortisone compound in a composition which includes a stabilizer comprising an omega-6 acid or an ester of an omega-6 acid.

15. The method of claim 13, wherein the step of adding said stabilizer comprises adding said stabilizer in an amount so that the omega-6 acid component thereof is at least equimolar to a quantity of said hydrocortisone 17-butyrate.

16. A stabilized hydrocortisone composition comprising:

a 17-substituted hydrocortisone; and

a stabilizer comprising an omega-6 acid or an ester of an omega-6 acid.

17. The composition of claim 16 wherein said 17-substituted hydrocortisone is a 17-substituted ester of hydrocortisone.

18. The composition of claim 16, wherein said 17-substituted hydrocortisone is 17-hydrocortisone butyrate.

19. The composition of claim-16, wherein said stabilizer is present in an amount so that the omega-6 acid component thereof is at least equimolar with the 17-substituted hydrocortisone.

20. A stabilized composition comprising:

hydrocortisone 17-butyrate; and

a stabilizer comprising an omega-6 acid or an ester of said omega-6 acid;

wherein said stabilizer is present in an amount such that the molar concentration of the omega-6 acid component thereof is greater than the molar concentration of said hydrocortisone butyrate.

21. The composition of claim 20, wherein said stabilizer comprises safflower oil.

22. The composition of claim 21, wherein the weight percentage of said safflower oil is at least ten times greater than the weight percentage of said hydrocortisone butyrate.