Treatment of wrinkling

Abstract: Skin suffering from intrinsic or photoaging wrinkling is treated with aliphatic mono- or dicarboxylic acids having 7 to 13 carbon atoms, the salts or monoglyceride or monosucrose esters thereof.

Description: BACKGROUND AND SUMMARY OF THE INVENTION This invention relates to the treatment of wrinkling of the skin. In particular, this invention is directed toward conditions involving photoaging or dermatoheliosis. The present invention resides in the discovery that certain mono- and dicarboxylic acids and their esters are effective in the treatment of these conditions, and represents a departure from the types of skin conditions on which such acids have previously been effective. U.S. Patents Nos. 4,292,326 (Nazarro-Porro, September 29, 1981) and 4,386,104 (Nazarro-Porro, May 31, 1983) disclose the use of dicarboxylic acids in the treatment of acne and melanocytic hyperpigmentary dermatoses. EP-A-0 273 202 which is not a prior publication discloses the use of hydroxycarboxylic acids and related ketocarboxylic acids and ester, lactone and salts forms thereof in compositions for the treatment of dermatologic disorders, e.g. dry skin, acne, hair loss, and wrinkles. DATABASE WPI, week 4881, Derwent Publications Ltd., London GB; AN 81-87956D describes a cosmetic skin cleaner composition to remove the strains in skin pores, to detach aged skin cells and to improve the blood circulation under the skin, Moreover, it is stated that the formation of wrinkles can be prevented. Wrinkling of the skin results from a combination of intrinsic thinning and photoaging (dermatoheliosis), with the latter being the primary cause. One compound, transretinoic acid, has been proven to reverse such structural damage with topical application. These are examples of conditions for which it has been discovered that dicarboxylic acids within the scope of the present invention are an effective treatment when applied topically. DETAILED DESCRIPTION OF THE INVENTION The mono- and dicarboxylic acids of the present invention are those having 7 to 13 carbon atoms, Hydoxycarboxylic acids and ketocarboxylic acids and the salts thereof are excluded. Preferred such acids are saturated aliphatic acids, particularly straight-chain species. Examples include azelaic (1,9-nonanedioic) acid, suberic (1,8-octanedioic) acid, sebacic (1,10-decanedioic) acid, and pimelic (1,7-heptanedioic) acid. The invention also extends to salts such as, for example, sodium, and are monoglycerides and sucrose monoesters. The compounds are generally applied in dermatological formulations. These include any of the various known mixtures and combinations which may be applied topically and which will permit even spreading of the active ingredient over the affected area. Examples include creams, lotions, solutions, ointments and unguents. The concentration of the mono- or dicarboxylic acid in the formulation is not critical and may vary over a wide range. The acid concentration may indeed range as high as the upper limit of dissolvability in any given formulation. In most cases, however, best results are achieved within a range of about 0.1% to about 40% by weight, preferably from about 3% to about 20% by weight. The formulation may contain additional ingredients on an optional basis, including both those which are biologically active and those which are biologically inactive. Examples of inactive ingredients are wetting agents, surfactants, emollients, solvents, keratolytics, and percutaneous absorption enhancers. The term "therapeutically effective amount" is used herein to denote any amount which will cause a substantial improvement or change in the condition for which it is applied when applied to the affected area repeatedly over a period of time. The amount will vary with the condition being treated, the stage of advancement of the condition, and the type and concentration of formulation applied. Appropriate amounts in any given instance will be readily apparent to those skilled in the art or capable of determination by routine experimentation. The compositions are generally applied in topical manner to the affected area, i.e., localized application to the skin region where the clinical abnormality is manifest. The following examples are offered for illustrative purposes, and are intended neither to limit nor define the invention in any manner. Formulation A: One pound of Cetaphil cream and 90 grams of azelaic acid were heated separately until each was liquified (approximately two hours). Cetaphil cream is a commercially available nonprescription mixture of water, ethyl alcohol, propylene alcohol, sodium lauryl sulfate, stearyl alcohol, methylparaben, propylparaben and butylparaben obtainable from Owen Laboratories, San Antonio, Texas. Once the cream and acid were liquified, the acid was slowly beat into the cream to form a smooth homogeneous cream. EXAMPLE 2 - APPLICATION Three patients, one male physician age 72 and two women ages 66 and 67 each applied Formulation A once daily for between nine and eleven and one-half months to treat and prevent sun-induced facial precancers and sebhorreic dermatitis. All three remarked that in addition to the correction of these conditions, the formulation improved the skin texture and the suppleness of their face skin. Examination confirmed these observations; two were further supported by photographic evidence.

Claims: Use of a compound selected from aliphatic mono- and dicarboxylic acids having 7 to 13 carbon atoms, the salts thereof, the monogyceride and monosucrose esters thereof for the manufacture of a medicament for the treatment of wrinkling of the skin, hydroxycarboxylic and ketocarboxylic acids and the salts thereof being excluded. Use according to claim 1 wherein said compound is selected from azelaic acid, the monoglyceride esters and the monosucrose ester thereof. Use according to claim 2 wherein said compound is azelaic acid. Use according to anyone of claims 1 to 3 wherein the medicament is a dermatological formulation containing from 0.1 % to 40 % by weight of said compound. Use according to claim 4 wherein the formulation contains 3 % to 20 % by weight of said compound.

Inventors: THORNFELDT CARL RICHARD, THORNFELDT, CARL RICHARD
Applicants: CELLEGY PHARMA INC, CELLEGY PHARMACEUTICALS, INC.
Application year: 1988
Main classification: A61K31
IPC codes: A61Q19, A61K8, A61K31