33 Lipomelanin sunscreen composition

• US 5,750,093 A
• Filed: 06/25/1997
• Issued: 05/12/1998
• Est. Priority Date: 04/30/1993
• Status: Expired due to Term

• Current Assignee: DUSA Pharmaceuticals Incorporated (Sun Pharmaceutical Industries Limited)
• Original Assignee: DUSA Pharmaceuticals Incorporated (Sun Pharmaceutical Industries Limited)
• Inventors: Menon, I. Aravindakshan, Haberman, Herbert F.
• Primary Examiner(s): Dodson, Shelley A.
• Application Number:
  US08/882,697
• Time in Patent Office: 321 Days
• Field of Search: 424/59, 514/553, 514/558, 554/80
• US Class Current: 424/59
• CPC Class Codes: A61K 2800/57 Compounds covalently linked to a(n inert) carrier molecule, e.g. conjugates, pro-fragrances
• CPC Class Codes: A61K 8/35 Ketones, e.g. benzophenone
• CPC Class Codes: A61K 8/445 aromatic, i.e. the carboxylic acid directly linked to the aromatic ring
• CPC Class Codes: A61K 8/72 containing organic macromolecular compounds
• CPC Class Codes: A61Q 17/04 Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
• CPC Class Codes: C09B 69/104 containing an indole dye, including melanine derivates

Abstract

A novel lipomelanin sunscreen complex includes melanin linked to a lipid to form a lipomelanin. One or more ultra-violet-light absorbing compounds can be added to form a lipomelanin sunscreen complex. A method for making the complex includes the oxidization of DOPA in the presence of a lipid and one or more ultra-violet absorbing compounds to form a mixture and precipitating the complex from the mixture by the addition of acid. The lipomelanin sunscreen complex provides protection against harmful ultra-violet radiation. The level of UV protection may be varied according to the presence and properties of the ultra-violet absorbing compounds in the complex.

Claims

1. A lipomelanin sunscreen comprising a melanin compound substantially chemically bound to a substantially unsaturated lipid to form a lipomelanin in combination with an ultraviolet radiation absorbing compound, and wherein said unsaturated lipid is selected from the group consisting of unsaturated fats, fatty acids, phosphoglycerides, or a combination of one or more of the same.

2. The sunscreen of claim 1, wherein the unsaturated lipid is selected from the group consisting of triglycerides, diglycerides, monoglycerides, esters of fatty acids, lecithins, cephalins, phosphatidyl ethanolamine, phosphatidyl dimethylethanolamine, phosphatidyl monomethylethanolamine, phosphastidyl inositol, phosphatidyl serine, phosphatidic acid, arachidonic acid, oleic acid, linoleic acid, linolenic acid, or a combination of one or more of the same.

3. The sunscreen of claim 1, wherein the unsaturated lipid comprises linoleic acid.

4. The sunscreen of claim 1 wherein said ultraviolet radiation absorbing compound is substantially physically entrapped within the lipomelanin molecules.

5. The sunscreen of claim 1 wherein the ultraviolet radiation absorbing compound is selected from the group consisting of paba, butyl paba, cinoxate, diethanolamine p-methoxycinnamate, digalloyl trioleate, dioxybenzone, amyl dimethyl paba, homomenthyl salicylate, ethyl 4-aminobenzoate, ethyl 4-(bis(hydroxypropyl)) aminobenzoate, 2-ethyl-hexyl 2-cyano-3, 3-dephenylacrylate, ethyl-hexyl p-methoxycinnamate, 2-ethyl-hexyl salicylate, glycerol aminobenzoate, homosalate, lawsone with dihydroxyacetone, menthyl anthranilate, PADIMATE A, PADIMATE O, 2-phenylbenzimidazole 5-sulfonic acid, red petrolatum, acetylsalicylic acid, triethanolamine salicylate, octyl dimethyl paba, glycerol paba, 2-hydroxy-4-methoxy-5-sulfobenzophenone (trihydrate) (sulisobenzone), butyl methoxy benzoylmethane (PARSOL 1789), 4-tert-butyl-4'"'"'-methoxy-dibenzoylmethane, 2-hydroxy-4-methoxybenzophenone (oxybensone), isoamyl dimethyl paba ester, 4-hydroxycinnamic acid, benzophenone, polymers thereof and combinations thereof.

6. The sunscreen of claim 1 wherein the unsaturated lipid is linoleic acid and the ultraviolet radiation absorbing compound is paba.

7. The sunscreen of claim 1 in combination with an adjuvant accaptable for application to human skin.

8. The sunscreen of claim 7 wherein said adjuvant comprises one or more compounds selected from the group consisting of mineral oil, jojoba oil, mink oil, emollients, vitamins, fragrances, dyes, coloring agents, pigments, and water.

9. A method for creating a lipomelanin sunscreen comprising the steps:

dissolving in water a compound selected from the group of melanin precursors consisting of DOPA and DOPA analogs, whereby an aqueous solution is formed having a concentration of about 10 to about 20 millimoles per liter;

adding to the solution of melanin precursors a solution containing a substantially unsaturated lipid and one or more ultraviolet radiation absorbing compounds to form a reaction mixture containing a concentration of about 6 to about 12 millimoles unsaturated lipid per liter, said unsaturated lipid selected from the group consisting of substantially unsaturated fats, phosphoglycerides, fatty acids or a combination of the same;

reacting the reaction mixture in the presence of oxygen for a sufficient period of time to form a solution containing lipomelanin sunscreen; and

isolating the lipomelanin sunscreen from the solution.

10. The method of claim 9 wherein said ultraviolet radiation absorbing compound is selected from the group consisting of:

paba, butyl paba, cinoxate, diethanolamine p-methoxycinnamate, digalloyl trioleate, dioxybenzone, amyl dimethyl paba, homomenthyl salicylate, ethyl 4-aminobenzoate, ethyl 4-(bis(hydroxypropyl)) aminobenzoate, 2-ethyl-hexyl 2-cyano-3, 3-dephenylacrylate, ethyl-hexyl p-methoxycinnamate, 2-ethyl-hexyl salicylate, glycerol aminobenzoate, homosalate, lawsone with dihydroxyacetone, menthyl anthranilate, PADIMATE A, PADIMATE O, 2-phenylbenzimidazole 5-sulfonic acid, red petrolatum, acetylsalicylic acid, triethanolamine salicylate, octyl dimethyl paba, glycerol paba, 2-hydroxy-4-methoxy-5-sulfobenzophenone (trihydrate) (sulisobenzone), butyl methoxy benzoylmethane (PARSOL

     1789), 4-tert-butyl-4'"'"'-methoxy-dibenzoylmethane, 2-hydroxy-4-methoxybenzophenone (oxybensone), isoamyl dimethyl paba ester, 4-hydroxycinnamic acid, benzophenone, polymers thereof and combinations thereof.

11. The method of claim 9 wherein the DOPA analogs are selected from the group consisting of hydroquinone, cathechol, o-quinone, p-quinone, DOPA methyl ester, dihydroxyphenylacetic acid, dihydroxyphenyl glycol and dihydroxyphenyl serine.

12. The method of claim 9, wherein the unsaturated lipid is linoleic acid.

13. The method of claim 9, wherein reacting the reaction mixture comprises the steps:

adding an enzyme to the reaction mixture; and

agitating the reaction mixture in the presence of oxygen.

14. The method of claim 13 wherein the enzyme comprises tyrosinase.

15. The method of claim 14 wherein the concentration of said tyrosinase in the reaction Mixture is about 20 to about 21 millimoles/liter, and the activity of said tyrosinase is about 3,310 to about 3,870 units per milligram.

16. The method of claim 15 wherein the pH of the reaction mixture is maintained at about 6.7 by using a phosphate buffer in a concentration of about 0.05 moles per liter, and the temperature of the reaction mixture is maintained at about 37 degrees centigrade for a period of about 16 hours.

17. The method of claim 9 wherein reacting the reaction mixture comprises the steps:

controlling the pH in the range of about 6 to about 10; and

agitating the reaction mixture in the presence of oxygen.

18. The method of claim 17 wherein the pH is controlled within a range of about 8 to about 10.

19. The method of claim 17 wherein the pH is controlled using a phosphate buffer at a pH of about 8.

20. The method of claim 17 wherein the step of agitating the reaction mixture in the presence of oxygen is performed by bubbling air through the reaction mixture.

21. The method of claim 17 wherein the reaction continues for at least about 12 to about 16 hours.

22. A method for producing a lipomelanin sunscreen by the autooxidization of a melanin precursor in the presence of an unsaturated lipid and an ultraviolet radiation absorbing compound, comprising the steps:

dissolving in water a compound selected from the group of melanin precursors, whereby an aqueous solution having a concentration of about 10 to about 20 millimoles melanin precursor per liter is formed;

adding a solution containing an unsaturated lipid which is a fat, phosphoglyceride or fatty acid, or a combination thereof, and one or more ultraviolet radiation absorbing compounds, to the aqueous solution to form a concentration of about 6 to about 7 millimoles lipid per liter to form a reaction mixture;

adding to the reaction mixture an ultraviolet radiation absorbing compound;

reacting the reaction mixture in the presence of oxygen for at least about 12 to about 16 hours to form a lipomelanin sunscreen in which the unsaturated lipid is substantially chemically bound to melanin, and in which the ultraviolet radiation absorbing compound is physically entrapped within the molecules of the lipomelanin.