Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1994-10-18
1997-10-07
Peselev, Elli
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
536 41, 536 185, 536 186, 536122, 536124, A61K 3170, C07H 100, C07H 1500
Patent
active
056748523
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel water-soluble sugar retinoids in which the sugar radical carries at least one sulfate group, and to their preparation and the use thereof as medicaments and in the cosmetic sector.
Retinoic acid derivatives are commonly used in the field of dermatology. Thus keratinising epithelial tissue can be converted by retinoic acid or derivatives thereof into tissue of normally differentiated cells. The retinoids exert a protective action against chemically, photochemically or virally induced carcinogenesis and assume protective functions in cell division. Retinoic acid itself is water-insoluble and is therefore usually converted into a water-soluble form for ease of handling.
Aromatic retinoids having a saccaride or aminosaccharide radical, and which are suitable dermatalogical agents for use in pharmaceuticals and cosmetics, are disclosed in U.S. Pat. No. 4,565,863. For toxicological reasons, such aromatic retinoids are sought to be avoided.
Accordingly, the invention relates to water-soluble aliphatic derivatives of retinoic acid. These novel retinoids are retinoic acid esters of formula (I) ##STR1## wherein X is a sugar residue attached at an oxygen atom, i.e. a mono-, di- or oligosaccharide which is sulfated at one or more than one OH group.
The double bonds in the retinoic acid radical may be in cis- or trans-configuration, the all-trans-form being preferred.
Oligosaccharides containing more than two sugar units may suitably be in particular compounds such as streptomycin, neuramic acid, fucose, .alpha.,.beta.,.gamma.-cyclodextrin, raffinose or short-chain degradation products of amylose or cellulose.
The sugar radical is preferably a mono- or disaccharide which is derived from ribose, arabinose, xylose, glucose, mannose, galactose, lactose, saccharose, trehalose, cellobiose, maltose, fructose or derivatives thereof, wherein at least one OH group is substituted by OSO.sub.3 M.
Suitable derivatives of these sugars include:
desoxy sugar; the lactones of the corresponding sugar acids such as gluconic acid .gamma.-lactone which in turn may be esterified by C.sub.1 --C.sub.4 alkyl; uronic acids; amino sugars having an unsubstituted amino group, typically glucosamine, fructosamine, galactosamine, or having a C.sub.1 --C.sub.6 alkyl-- or C.sub.1 --C.sub.6 acetyl-substituted amino group, e.g. aminoethyl-glucosides, aminoethyl-2-deoxy-2-aminoglucoside, N-acetylaminoglucoside; sugars in which the OH groups are substituted by one or more than one C.sub.1 --C.sub.4 alkoxy group, e.g. methyl or ethyl glucose, substitution by C.sub.1 --C.sub.4 alkylene bridges also being possible; keto-sugar acids such as ascorbic acid; sugars in which the OH groups are mono- or polyacetylated, typically glucose acetate or 2,3,4-tri-O-acetylglucose; or sugars carrying several different substituents, e.g. neuraminic acid.
Particularly preferred sugars are glucose, galactose, mannose or derivatives thereof.
The aforementioned sugar radicals may also be in the form of racemates or any mixtures of the (L)- and (D)-configuration as well as in the form of the pure (L)- or (D)-isomers. The natural (D)-configuration is preferred.
The sulfate group introduced into the sugar radiacal may be in the form of the free acid or the salt OSO.sub.3 M. The counterion M may suitably be hydrogen, an alkali metal ion, an alkaline earth metal ion or NZ.sub.4, where Z is hydrogen; C.sub.1 --C.sub.4 alkyl such as methyl or ethyl; C.sub.2 --C.sub.4 hydroxyalkyl such as 2-hydroxyethyl; or aryl. Compounds in which M is hydrogen or an alkali metal ion are preferred, with hydrogen, sodium and potassium being especially preferred.
Compounds of formula Ia, Ib or Ic are of particular importance: ##STR2## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are OH, OSO.sub.3 M, C.sub.1 --C.sub.4 alkoxy, C.sub.1 --C.sub.3 --COO--, or two of these radicals taken together are a O--C.sub.1 --C.sub.4 --O--alkylene bridge, and with the proviso that at least one radical is OSO.sub.3 M; ; saccharide moiety is in the furanose form.
Compounds of formul
REFERENCES:
patent: 4457918 (1984-07-01), Holick et al.
patent: 4565863 (1986-01-01), Bollag et al.
patent: 5091371 (1992-02-01), Lakeuchi et al.
Internation Journal for Vitamin and Nutrition Research Bd. 61, 1991, Seiten pp. 258-263, A B Barua et al.
Luther Helmut
Maier Thomas
Ciba-Geigy Corporation
Mansfield Kevin T.
Peselev Elli
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