Title:  Method and compositions for topical treatment of damaged tissue using reactive oxygen metabolite production or release inhibitors

United States Patent:  6,270,781

Assignee:  Maxim Pharmaceuticals, Inc. (San Diego, CA)

Filed:  January 8, 1999

The present invention relates to compositions and methods for treating cell damage caused by reactive oxygen species in relation to a variety of skin disorders. More specifically, the present invention relates to the treatment skin disorders through the topical delivery of reactive oxygen metabolite production or release inhibiting compounds.

SUMMARY OF THE INVENTION

The present invention is directed to methods and compositions for reducing enzymatically produced ROM-mediated damage to a subject's skin or mucosal membranes by the topical application of ROM production and release inhibiting compositions. One embodiment of the present invention is a method for inhibiting and reducing enzymatically produced ROM-mediated oxidative damage to a subject's skin or mucosal membranes comprising the step of topically delivering an effective dose of a ROM production and release inhibitory compound in a pharmaceutically acceptable carrier to a subject suffering from ROM-mediated oxidative damage to said subject's skin or mucosal membranes.

In one aspect of this embodiment, the ROM-mediated oxidative damage to said subject's skin or mucosal membranes is a viral disease selected from the group consisting of herpes labialis, herpes genitalis, herpes zoster, and varicella zoster. In another aspect, the ROM-mediated oxidative damage to said subject's skin or mucosal membranes results from an injury selected from the group consisting of photodermatitis, thermal burns, lacerations, and cosmetic surgery.

In another embodiment of the present invention the ROM production and release inhibitory compound is selected from the group consisting of histamine, histamine dihydrochloride, histamine diphosphate, other histamine salts, esters, prodrugs, H₂ receptor agonists, serotonin, and 5HT agonists. In another embodiment, the ROM production and release inhibitory compound is a compound that promotes the release of endogenous histamine stores. In an aspect of this embodiment, compounds that promote the release of endogenous histamine stores are selected from the group consisting of IL-3, retinoic acid, 9-cis-retinoic acid, all-trans-retinoic acid, and allergens.

Another embodiment of the present invention contemplates a composition comprising an effective dose of a compound that inhibits the production or release of enzymatically produced ROMs in a pharmaceutically acceptable carrier adapted for topical delivery. In one aspect of this embodiment, the compound is selected from the group consisting of histamine, histamine dihydrochloride, histamine diphosphate, other histamine salts, esters, prodrugs, H₂ receptor agonists, serotonin, and 5HT agonists. In another aspect, the compound is a compound that promotes the release of endogenous histamine stores. In still another aspect, the compound that promotes the release of endogenous histamine stores is selected from the group consisting of IL-3, retinoic acid, 9-cis-retinoic acid, all-trans-retinoic acid, and allergens. In still another aspect of this embodiment, the pharmaceutically acceptable carrier is a cosmetic product, such as a sunscreen, a toothpaste, a soap, a wound dressing, a spray, a mouthwash, or a transdermal patch.

In still another embodiment of the present invention, a method for making a composition for topically delivering histamine comprising the steps of providing a pharmaceutically acceptable carrier and histamine in a concentration effective to treat a ROM mediated damage to the skin or mucosa caused by a disorder of the skin or mucosa selected from the group consisting of herpes labialis, herpes genitalis, herpes zoster, varicella zoster, photodermatitis, thermal burns, cosmetic surgery and periodontal disease, and forming a composition containing the pharmaceutically acceptable carrier and a compound that inhibits the production and release of enzymatically produced ROMs.

In yet another embodiment of the present invention, the making of the compositions involves selecting the compound from the group consisting of histamine, histamine dihydrochloride, histamine diphosphate, other histamine salts, esters, prodrugs, H₂ receptor agonists, serotonin, and 5HT agonists. In another embodiment, the claimed methods of the present invention are within ROM production and release inhibitory compound is a compound that promotes the release of endogenous histamine stores.

Claim 1 of 9 Claims

What is claimed is:

1. A cosmetic composition comprising an effective dose of a compound that inhibits the enzymatic production or release of ROMs in a cosmetically acceptable carrier adapted for topical delivery as a cosmetic product, said carrier is selected from the group consisting of a makeup product, a hair care product, an underarm deodorant product, a perfume, a cologne, an aftershave, and a lotion.

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