UV-stable, liquid or semisolid transdermal pharmaceutical preparation with light sensitive active ingredient

• US 20050129756A1
• Filed: 12/07/2004
• Published: 06/16/2005
• Est. Priority Date: 12/10/2003
• Status: Abandoned Application

• Current Assignee: Schering Ag (Merck & Co., Inc.)
• Original Assignee: Schering Ag (Merck & Co., Inc.)
• Inventors: Bracht, Stefan, Podhaisky, Hans-Peter
• Application Number:
  US11/006,434
• Publication Number:
  US 20050129756A1
• Time in Patent Office: Days
• US Class Current: 424/464
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• 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 47/32 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

Abstract

The semisolid or liquid pharmaceutical preparation for transdermal administration contains at least one UV-light sensitive pharmaceutically active ingredient and at least one UV-absorbing substance, which is present in an amount that does not have pharmacological activity and in dissolved or dispersed form. This semisolid of liquid pharmaceutical preparation is preferably a hydroalcoholic gel, whose gel base includes water, alcohol, at least one gel-forming polymer and additional ingredients as needed. This pharmaceutical preparation is prepared with a UV-light sensitive pharmaceutically active ingredient, so that the application system has a high stability without the disadvantages of the known semisolid transdermal application forms. The injurious side effects, such as absorption of the UV-light protecting ingredient in the body, resulting from the intended light protection are reduced as much as possible.

Claims

1. A semisolid or liquid pharmaceutical preparation for transdermal administration, said preparation comprising at least one UV-light sensitive pharmaceutically active ingredient and at least one UV-absorbing substance, wherein the at least one UV-absorbing substance is present only in an amount such that the at least one UV-absorbing substance does not have pharmacological activity and is present in dissolved or dispersed form.

2. The semisolid or liquid pharmaceutical preparation as defined in claim 1, consisting of a hydroalcoholic gel.

3. The semisolid or liquid pharmaceutical preparation as defined in claim 1, wherein said at least one UV-absorbing substance has a distribution coefficient (Log P) either greater than 3.0 or less than 1.0.

4. The semisolid or liquid pharmaceutical preparation as defined in claim 3, wherein said distribution coefficient is greater than 5.0 or less than 0.0.

5. The semisolid or liquid pharmaceutical preparation as defined in claim 1, wherein said at least one UV-absorbing substance has a molecular mass greater than 250 g/mol.

6. The semisolid or liquid pharmaceutical preparation as defined in claim 5, wherein said molecular mass is greater than 500 g/mol.

7. The semisolid or liquid pharmaceutical preparation as defined in claim 1, wherein said at least one UV-absorbing substance is present in an amount of from 1 to 10% by weight, based on a total amount of non-volatile ingredients present.

8. The semisolid or liquid pharmaceutical preparation as defined in claim 7, wherein said amount of said at least one UV-absorbing substance is from 2 to 5% by weight, based on said total amount of said non-volatile ingredients present.

9. The semisolid or liquid pharmaceutical preparation as defined in claim 1, wherein said at least one UV-absorbing substance, which absorbs in a UV spectral range, is p-aminobenzoic acid, 4-dimethylaminobenzoic acid-2-ethyl-hexyl ester, 4-bis-(polyethoxy)-aminobenzoic acid polyethoxyethyl ester, cinnamic acid, 4-methoxycinnamic acid isoamyl ester, 4-methoxycinnamic acid-2-ethylhexylester, 3-benzylidenebornan-2-one, 3-(4′

)-methylbenzyliden-bornan-2-one, 3-(4-sulfo)-benzylidenebornan-2-one, 3-(4′

-trimethylammonium)-benzylidenbornan-2-one methyl sulfate, polymers of N-[2-(2-oxoborn-3-ylidenmethyl)benzyl]acrylamide, polymers of N-[4-(2-oxoborn-3-ylidene-methyl)benzyl]acrylamide, 4-isopropyl-benzylsalicylate, salicylic acid-2-ethylhexylester and/or 3,3,5-trimethylcyclohexyl-salicylate.

10. The semisolid or liquid pharmaceutical preparation as defined in claim 1, wherein said at least one UV-absorbing substance, which absorbs in a UV spectral range, is 2,4,6-trianiline-p-(carbo-2′

-ethyl-hexyl-1′

-oxy)-1,3,5-triazine, dioctyl butamidotriazine, bis-ethylhexyl-oxyphenol methoxyphenyltriazone, 3-imidazol-4-yl-acrylic acid, esters of 3-imidazol-4-yl-acrylic acid, 2-phenylen-benzimidazol-5-sulfonic acid, 2,2′

-(1,4-phenylen)-bis-(1H-benzimidazol-4,6-disulfonic acid, monosodium salt), methylene bis-benzotriazolyl-tetramethyl-butylphenol, drometriazole trisiloxane, 2-cyano-3,3-diphenylacrylic acid, terephthaloylidene dicamphor sulfonic acid, butylmethoxydibenzoyl-methane, benzophenone, benzophenone-3, benzophenone-4 and/or 2,2′

-dihydroxy-4,4′

-dimethoxy-benzophenon-5,5′

-disodium sulfonate.

11. The semisolid or liquid pharmaceutical preparation as defined in claim 1, wherein said at least one UV-light sensitive pharmaceutically active ingredient is at least one hormone.

12. The semisolid or liquid pharmaceutical preparation as defined in claim 1, wherein said at least one UV-light sensitive pharmaceutically active ingredient is a gestagen.

13. The semisolid or liquid pharmaceutical preparation as defined in claim 12, wherein said gestagen is gestoden or levonorgestrel.

14. The semisolid or liquid pharmaceutical preparation as defined in claim 1, wherein said at least one UV-light sensitive pharmaceutically active ingredient is an estrogen.

15. The semisolid or liquid pharmaceutical preparation as defined in claim 14, wherein said estrogen is ethinyl estradiol.

16. The semisolid or liquid pharmaceutical preparation as defined in claim 1, wherein said at least one UV-light sensitive pharmaceutically active ingredient comprises a combination of gestagen and estrogen.

17. The semisolid or liquid pharmaceutical preparation as defined in claim 1, wherein said combination of said gestagen and said estrogen is a combination of gestoden and ethinyl estradiol.

18. The semisolid or liquid pharmaceutical preparation as defined in claim 1, wherein said at least one UV-light sensitive pharmaceutically active ingredient is an androgen.

19. The semisolid or liquid pharmaceutical preparation as defined in claim 18, wherein said androgen is testosterone, methyltestosterone, methyl-nor-testosterone (MENT) or 7α

-methyl-11 β

-fluoro-19-nortestosterone (ef-MENT).

20. The semisolid or liquid pharmaceutical preparation as defined in claim 1, in the form of a colorless and transparent preparation.

21. The semisolid or liquid pharmaceutical preparation as defined in claim 20, wherein said preparation is a gel.

22. The semisolid or liquid pharmaceutical preparation as defined in claim 1, 20 or 21, further comprising a gel former and wherein said gel former is hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, methylhydroxyethyl cellulose, methylhydroxypropyl cellulose, Na-carboxymethylcellulose, chitosan-EDTA, highly dispersed silicon dioxide, precipitated silicon dioxide, bentonite, corn starch, rice starch, potato starch, wheat starch, carboxymethylamylopectin-sodium, tragacanth, alginate, polyacrylate, polymethacrylate, polyacrylate-polyalkylacrylate cross polymer, acryloyldimethyl taurate/vinyl pyrrolidone copolymer, polyvinyl alcohol or polyvinyl pyrrolidone.

23. The semisolid or liquid pharmaceutical preparation as defined in claim 1, wherein said at least one UV-light sensitive pharmaceutically active ingredient penetrates or permeates human skin to a much greater extent and depth than said at least one said UV-absorbing substance during transdermal administration, so that said at least one UV-absorbing substance is contained in skin layers substantially above said at least one UV-light sensitive pharmaceutically active ingredient absorbed in said human skin, in order to at least reduce an amount of UV radiation reaching said at least one UV-light sensitive pharmaceutically active ingredient.

24. The semisolid or liquid pharmaceutical preparation as defined in claim 23, wherein said at least one UV-absorbing substance has a distribution coefficient (Log P) either greater than 3.0 or less than 1.0 and said at least one UV-absorbing substance has a molecular mass greater than 250 g/mol.

25. The semisolid or liquid pharmaceutical preparation as defined in claim 23, wherein said at least one UV-light sensitive pharmaceutically active ingredient is a steroid hormone.