Stabilized steroid composition and method for its preparation

• US 7,981,877 B2
• Filed: 05/11/2006
• Issued: 07/19/2011
• 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.
• Primary Examiner(s): HUI, SAN MING R
• Application Number:
  US11/432,742
• Publication Number:
  US 20060205703A1
• Time in Patent Office: 1,895 Days
• Field of Search: 514/182
• US Class Current: 514/182
• 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 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.

2. The method of claim 1, wherein the stabilizer comprises linoleic acid.

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

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 is at least equimolar to a quantity of said hydrocortisone 17-butyrate.

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

7. A method for stabilizing a hydrocortisone compound comprising hydrocortisone 17-butyrate, 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;

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.

8. The method of claim 7 wherein the stabilizer comprises safflower oil.

9. A stabilized hydrocortisone composition comprising:

17-hydrocortisone butyrate; and

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

10. The composition of claim 9, wherein said stabilizer is present in an amount so that the omega-6 acid component thereof is at least equimolar with the hydrocortisone 17-butyrate.

11. 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.

12. The composition of claim 11, wherein said stabilizer comprises safflower oil.

13. The composition of claim 12, wherein the weight percentage of said safflower oil is at least ten times greater than the weight percentage of said hydrocortisone butyrate.