WO1986000014A1

WO1986000014A1 - Topical compositions

Info

Publication number: WO1986000014A1
Application number: PCT/US1985/001066
Authority: WO
Inventors: Murray Weiner
Original assignee: Individual
Current assignee: Individual
Priority date: 1984-06-11
Filing date: 1985-06-10
Publication date: 1986-01-03
Anticipated expiration: 1986-12-11
Also published as: AU4430685A; EP0182881A1

Abstract

Topical compositions of urea, useful for the prevention and/or reduction of skin damage caused by ultraviolet radiation.

Description

TOPICAL COMPOSITIONS

This invention relates to topical compositions for the prevention and/or reduction of skin damage caused by ultraviolet radiation. In particular this invention relates to the prevention and/or reduction of skin damage caused by reactive chemical substances generated in the skin by ultraviolet radiation.

The health promoting qualities of sunlight have been recognized throughout history. However, in recent years, medical professionals and the lay public both have become awre of the skin diseases and degenerative processes that occur from prolonged and excessive exposure to ultra¬ violet (UV) radiation. Depending on skin types, even modest exposure can be damaging and dangerous. The mechanisms by which ultraviolet radiation exerts its adverse effects on the skin are not fully understood. They are believed to involve absorption of light energy by skin tissue components to produce very reactive substances such as free radicals. In particular, they involve the production in the skin tissue of nitroso, nitrite, and other mediators of undesired skin changes in sensitive individuals. The potential of nitrites to react with and damage tissue is well recognized. Recent experiments in vitro and in vivo have shown the contribution of nitrites to structual alteration of integumental (skin) structures.

Prior art topical compositions-for the prevention of UV induced skin damage-are essentially sunscreens in that they absorb light particularly in the ultraviolet wave lengths associated with skin damage. Even with the broad spectrum of sunscreen preparations available, ranging from modest to essentially complete UV blockage, serious problems of sun damaged skin persist. These sunscreens are not effective in reducing the formation of free radical substances such as nitrate reduction products in the skin tissue from UV light that does reach the skin. Furthermore, they do not hve any effect on the damaging interactions in the skin tissue caused by the free radicals produced. The present invention provides a topical urea compo¬ sition, for prevention of skin damage due to ultraviolet radiation.

Since urea has no ultraviolet light absorbing pro¬ perties in the skin damaging light wave lengths of 290 to 400 mm, it is not a sunscreen agent. Its skin protective properties are as a neutralizer of damaging active chemical entities. Urea moderates the effects of nitrate reduction products, thus preventing skin damage following ultraviolet radiation. The concentration of urea which may be used in the topical compositions is from about 0.1% to about 40%, preferably from about 1% to about 20% based on the weight of the composition.

It is a further embodiment of this invention to use chemical analogs of urea which have functional urea substitutions, in the topical compositons.

In a preferred embodiment of this invention urea may be combined with known UV absorbing sun screen agents such as Padimato 0 (2-ethylhexyl-p-dimethyl amino- benzoate), Oxybenzone (2-hydroxy-4-methoxy benzophenone) and paraaminobenzoic acid (PABA) in topical compositions. This combination of UV absorbing agents and urea free radical neutralizer, provides a superior skin protecting agent to that of the prior art. The UV absorbing agent may be present in the topical composition from about 1% to about 10% by weight of the composition.

The topical compositions of this invention are preferably applied to the skin in the form of conven- tional alcoholic lotions, liquid emulsions, creams, transparent gels, or aerosol sprays. EXAMPLE

The following ingredients were blended to form topical cream compositions (A, B, C, D and E) using conventional methods.

Percent w/w

Ingredients A B C D E

Mineral Oil 5-20 5-20 5-20 5-20 5-20 Isopropyl Myristate 0-10 0-10 0-10 0-10 0-10

Acetylated Lanolin 0- 10 0- 10 0-10 0-10 0-10 Alcohol

Cetyl Alcohol 1-10 1-10 1-10 1-10 1-10

Glycerol Mono- stearate 1-10 1-10 1-10 1-10 1-10

Tween 80 0-5 0-5 0-5 0-5 0-5

Methyl Paraffin 0.5 0. 5 0.5 0.5 0.5

Propyl Paraffin 0.2 0.2 0.2 0.2 0.2

Carbopol 934 0. 1 0. 1 0. 1 0. 1 0. 1 (Polyacrylic acid)

Sodium Hydroxide 0-0.1 0-0.1 0-0.1 0-0.1 0-0.1

Propyleneglyco1 0-5 0-5 0-5 0-5 0- 5

Urea 15 15 15

Padimate 0 - 1.4-8 1.4-8 - - (2-ethylhexyl-p-di- methyl amino- benzoate)

Oxybenzone __ _. _. 2-6 2-6

(2-Hydroxy-4-Methoxy Benzophenone)

Water q.s. q.s. q.s. q.s. q.s.

Total 100 100 100 100 100 In a study of ultraviolet light induced acute and chronic actinic damage, it was found that the urea compositions of this invention (e.g., compositions A, C and E) provided a significant degree of protection against acute sunburn damage in hairless mouse skin as compared with placebo compositions. Using SK-1 hairless mice, observations were made of erythema responses under blinded conditions. There were striking differences in H and E stained tissue sections taken from the reaction sites. The skin damage in placebo treated sites was two to three times greater than the urea composition treated sites, based upon thickness of the epidermis, the number of sunburn cells noted, and the dermal inflammatory changes.

Claims

WHAT IS CLAIMED IS:

1. A method for the prevention and/or reduction of skin damage caused by ultraviolet rdiation which comprises topically applying a composition of a therapeutically effective amount of urea in a pharmaceutically acceptable carrier to the skin of an individual in need of such skin treatment.

2. The method according to claim 1 wherein the amount of urea is from about 0.1 to about 40 percent based on the weight of the composition.

3. The method according to claim 2 wherein the amount of urea is from 1 to about 20 percent.

4. The method according to claim 1 wherein an ultraviolet radiation absorbing agent is present in the composition.

5. The method according to claim 4 wherein the ultraviolet radiation absorbing agent is 2-ethyl- hexyl-p-dimethyl aminobenzoate, 2-hydroxy-4-methoxy benzophenoue, or para-aminobenzoic acid.

6. The method according to claim 5 wherein the amount of ultraviolet absorbing agent is from about 1 to about 10 percent based on the weight of the composition.

7. A composition for the prevention and/or reduction of skin damage caused by ultraviolet radiation which comprises a therapeutically effective amount of urea and a therapeutically effective amount of an ultraviolet radiation absorbing agent.

8. The composition according to claim 7 wherein the ultraviolet radiation absorbing agent is 2-ethylhexyl-p- dimethyl aminobenzoate, 2-hydroxy-4-methoxy benzophenone, or para-aminobenzoic acid.

9. The composition according to claim 7 wherein the amount of urea is from about 0.1 to about 40 percent, and the ultraviolet radiation absorbing agent is from about 1 to about 10 percent, based on the weight of the composition.

10. The composition according to claim 7 wherein the amount of urea is from about 1 to about 20 percent.

11. The composition according to claim 8 wherein the amount of ultraviolet absorbing agent is from about 1-10 percent based on the weight of the composition.