Compositions and methods for enhancing corticosteroid delivery

• US 7,794,738 B2
• Filed: 01/24/2007
• Issued: 09/14/2010
• Est. Priority Date: 12/21/2001
• Status: Expired due to Fees

• Current Assignee: Medicis Pharmaceutical Corporation (Bausch Health Cos., Inc.)
• Original Assignee: Medicis Pharmaceutical Corporation (Bausch Health Cos., Inc.)
• Inventors: Gans, Eugene H., Wortzman, Mitchell S.
• Primary Examiner(s): HUI, SAN MING R
• Application Number:
  US11/657,893
• Publication Number:
  US 20070142344A1
• Time in Patent Office: 1,329 Days
• Field of Search: 514/170, 514177-180, 424/400
• US Class Current: 424/400
• 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 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 47/08 containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• 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: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: G11C 16/0433 comprising cells containing a single floating gate transistor and one or more separate select transistors
• CPC Class Codes: G11C 2216/10 Floating gate memory cells with a single polysilicon layer

Abstract

The present invention comprises a composition, method of enhancing potency and method of delivering corticosteroids in a vehicle comprising at least two penetration enhancers, and solvents and emulsifiers. The propylene glycol and penetration enhancers are present in ratio to the total of the propylene glycol, penetration enhancers, and solvents and emulsifiers of at least about 0.70.

Claims

1. A method of delivering corticosteroids to skin comprising:

Topically applying a composition comprising

one or more corticosteroids with two or more penetration enhancers, and one or more of the group consisting of solvents and emulsifiers, wherein the penetration enhancers are present in ratio to a total of the penetration enhancers, and solvents and emulsifiers of at least about 0.90, and wherein the penetration enhancers comprise two or more of the group consisting of propylene glycol, diisopropyl adipate, dimethyl isosorbide, 1,2,6 hexanetriol, and benzyl alcohol, and

wherein said composition does not include a monoglyceride of a C₆-C₁₀ medium chain fatty acid.

2. The method of claim 1 wherein the corticosteroid comprises a fluorinated corticosteroid.

3. The method of claim 1 wherein the corticosteroid comprises fluocinonide.

4. The method of claim 1 wherein the corticosteroid comprises fluocinolone acetonide.

5. The method of claim 1, 2, 3 or 4 wherein the corticosteroid is present at about 0.10%.

6. The method of claim 1, 2, 3 or 4 wherein the corticosteroid is present at least about 0.50%.

7. The method of claim 1, 2, 3 or 4 wherein the corticosteroid is present at least about 0.25%.

8. The method of claim 1 wherein the solvents and emulsifiers comprise one or more of the group consisting of dehydrated alcohol, alcohol (95% v/v)USP, 3-Cyclohexene-1-Methanol, 4-Dimethyl-a-(4-Methyl-3-Pentenyl)-, Steareth-2, Steareth-21, citric acid, CPE-215, diisopropanolamine (1:

9), DIPA/PG (1;

9), ethoxydiglycol, Potassium hydroxide (10%), PEG-40 Stearate, PEG-7000, Polysorbate 60, potassium hydroxide (1%), propylene carbonate USP, propylethylene glycol 4, oleyl alcohol, sodium lauryl sulfate, sorbitan monostearate, sorbitan stearate, and 1,2,3-Propanetriyl Ester.

9. The method of claim 1 wherein the composition further comprises one or more non-solvent/emulsifier ingredients.

10. The method of claim 9 wherein the non-solvent/emulsifier ingredients comprise one or more of the group consisting of Glyceryl Stearate (and) PEG-100 Stearate, carbopol 980, cyclomethicone NF, glyceryl monostearate, hydroxyethyl cellulose, hydroxypropyl cellulose, isopropyl myristate, methyl paraben NF, mineral oil, oleic acid NF, PEG-100 Stearate, petrolatum, propyl paraben NF, purified water, stearyl alcohol, white petrolatum, and white wax.

11. The method of claim 1 wherein the solvents and emulsifiers are present at about 4-5%.

12. The method of claim 10 wherein the non-solvent/emulsifier ingredients are present at about 11% to about 53%.

13. The method of claim 10 wherein the non-solvent/emulsifier ingredients are present at about 11% to about 27%.

14. A method of delivering corticosteroids to skin comprising:

Topically applying a composition comprising

one or more corticosteroids with two or more penetration enhancers, and one or more of the group consisting of solvents and emulsifiers, wherein the penetration enhancers are present in ratio to a total of the penetration enhancers, and solvents and emulsifiers of at least about 0.90, and wherein the first penetration enhancer is propylene glycol and the second penetration enhancer is selected from the group consisting of diisopropyl adipate, dimethyl isosorbide, 1,2,6 hexanetriol, and benzyl alcohol, and wherein the propylene glycol is at least 66.8% of the composition.

15. A method of delivering corticosteroids to skin comprising:

Topically applying a composition comprising

one or more corticosteroids with two or more penetration enhancers, and one or more of the group consisting of solvents and emulsifiers wherein the penetration enhancers are present in ratio to a total of the penetration enhancers, and solvents and emulsifiers of at least about 0.90, and wherein the first penetration enhancer is propylene glycol and the second penetration enhancer is selected from the group consisting of diisopropyl adipate, dimethyl isosorbide, 1,2,6 hexanetriol, and benzyl alcohol, and wherein the propylene glycol is between 66.8% and 74.9% of the composition.

16. A method of delivering corticosteroids to skin comprising:

Topically applying a composition comprising one or more corticosteroids with two or more penetration enhancers, and one or more of the group consisting of solvents and emulsifiers, wherein the penetration enhancers are present in ratio to a total of the penetration enhancers, and solvents and emulsifiers of at least about 0.90, and wherein the first penetration enhancer is dimethyl isosorbide and the second penetration enhancer is selected from the group consisting of propylene glycol, diisopropyl adipate, 1,2,6 hexanetriol, and benzyl alcohol.

17. The method of claim 16 wherein the corticosteroid comprises a fluorinated corticosteroid.

18. The method of claim 16 wherein the corticosteroid comprises fluocinonide.

19. The method of claim 16 wherein the corticosteroid comprises fluocinolone acetonide.

20. The method of claim 16, 17, 18 or 19 wherein the corticosteroid is present at about 0.10%.

21. The method of claim 16, 17, 18 or 19 wherein the corticosteroid is present at at least about 0.50%.

22. The method of claim 16, 17, 18 or 19 wherein the corticosteroid is present at at least about 0.25%.

23. The method of claim 16 wherein the solvents and emulsifiers comprise one or more of the group consisting of dehydrated alcohol, alcohol (95% v/v)USP, 3-Cyclohexene-1-Methanol, 4-Dimethyl-a-(4-Methyl-3-Pentenyl)-, Steareth-2, Steareth-21, citric acid, CPE-215, diisopropanolamine (1:

9), DIPA/PG (1;

9), ethoxydiglycol, Potassium hydroxide (10%), PEG-40 Stearate, PEG-7000, Polysorbate 60, potassium hydroxide (1%), propylene carbonate USP, propylethylene glycol 4, oleyl alcohol, sodium lauryl sulfate sorbitan monostearate, sorbitan stearate and 1,2,3-Propanetriyl Ester.

24. The method of claim 16 wherein the composition further comprises one or more non-solvent/emulsifier ingredients.

25. The method of claim 24 wherein the non-solvent/emulsifier ingredients comprise one or more of the group consisting of Glyceryl Stearate (and) PEG-100 Stearate, carbopol 980, cyclomethicone NF, glyceryl monostearate, hydroxyethyl cellulose, hydroxypropyl cellulose, isopropyl myristate, methyl paraben NF, mineral oil, oleic acid NF, PEG-100 Stearate, petrolatum, propyl paraben NF, purified water, stearyl alcohol, white petrolatum, and white wax.

26. The method of claim 16 wherein the solvents and emulsifiers are present at about 4-5%.

27. The method of claim 24 wherein the non-solvent/emulsifier ingredients are present at about 11% to about 53%.

28. The method of claim 24 wherein the non-solvent/emulsifier ingredients are present at about 11% to about 27%.

29. The method of claim 16 wherein the second penetration enhancer is propylene glycol and wherein the propylene glycol is at least 66.8% of the composition.

30. The method of claim 16 wherein the second penetration enhancer is propylene glycol and wherein the propylene glycol is between 66.8% and 74.9% of the composition.