Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Patent
1993-03-02
1996-09-17
Henley, III, Raymond
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
514544, 514560, 514568, 514703, 514725, A61K 3107, A61K 3120, A61K 31235, A61K 31575
Patent
active
055568440
DESCRIPTION:
BRIEF SUMMARY
The present invention has for an object a pharmaceutical or cosmetic composition having a synergistic effect, intended principally for the treatment of epidermic keratinization disorders, epithelial or epidermic proliferation disorders, and/or disorders of the sebaceous function, the said composition comprising, in combination, at least one retinoid and at least one steroid that inhibits the biosynthesis of cholesterol.
It is known that agents controlling cellular differentiation, such as retinoids, are largely employed or envisioned for the treatment of keratinization disorders. These retinoids have principally the property of inhibiting the formation of cornified envelopes (CE) of the epidermis, that is to say, the last phase of the differentiation of keratinocytes. The mechanism of biological activity involved is known: it is a question of an inhibition of the expression of membranal transglutaminase (TGm) which is an essential enzyme in the synthesis of CE; see for example FEBS LETTERS, Vol. 258, No. 1, p. 35-38 (1989), Vol. 229 No. 1, p. 193-196 (1988) and Vol. 186, No. 2, p. 201-204 (1985), and J. Invest. Dermatol. Vol. 90, No. 4, p. 472-474 (1988).
It is also known that 25-hydroxy cholesterol is also capable of inhibiting the synthesis of CEs; see principally Exp. Cell. Res. 171, p. 426-435 (1987).
It has now been discovered that the inhibition of the synthesis of cornified envelopes by 25-hydroxy cholesterol results from a different biochemical mechanism: it is a question of an inhibition of the biosynthesis of cholesterol.
It has also been discovered that compositions containing, in combination, both a retinoid capable of inhibiting the expression of TGm and a sterol capable of inhibiting the biosynthesis of cholesterol exhibits a synergistic effect in that which concerns the inhibition of the synthesis of CEs.
These two types of compounds act by two independent biochemical ways, and it would normally be expected, with the combination, to obtain a resultant inhibiting activity of the synthesis of the CEs equal to the addition of the activities obtained with the compounds tested separately. However, it has now been discovered, in a surprising manner, that the combination mentioned above causes a synergism: the level of inhibition obtained is very sharply superior to the addition of the inhibitions due to the constituents of the combination taken separately.
The present invention has for an object a synergistic composition resulting from the combination of two agents controlling cellular differentiation by mechanisms of different activity, to treat or correct epidermic keratinization disorders, any other disorder or any other functions defect or excess of the epidermic or epithelial proliferation and/or disorders of the sebaceous function, accompanied or not by an inflammatory and/or immunoallergic component. The composition of the invention permits, for example, to treat conjunctive tissue degeneration diseases, benign or malignant tumors, to combat against skin aging, to favor cicatrization, or even to improve the appearance of the skin of persons exhibiting keratinization disorders.
The combination, according to the present invention, also finds use in the ophthalmologic field, principally in the treatment of corneopathies.
The use of this combination provides principally the advantage of permitting to obtain a sufficient activity all while sharply reducing the amount of the agent controlling cellular differentiation and, consequently, limiting or even suppressing, secondary effects due to this agent. There can thus be employed, for example, a compound having an activity of the retinoid type which is much less powerful, and consequently less toxic, than that of retinoic acid, and obtain however, thanks to the synergism, an equivalent activity.
The pharmaceutical or cosmetic composition having a synergistic effect of the invention comprises then, in combination,
The retinoids constitute a class of known compounds, which comprise vitamin A, its natural derivatives and all synthetic derivatives havi
REFERENCES:
patent: 4961922 (1990-10-01), Shroot et al.
Jetten et al., J. Invest. Dermatol., 92(2), 203-209. 1989.
Ponec et al., Experimental Cell Research 171 (1987) 426-435.
Reichert Uwe
Schmidt Rainer
Shroot Braham
Centre International De Recherches Dermatologiques Galderma (Cir
Henley III Raymond
Spivack P.
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