COSMETICAL PRODUCT

Abstract: The present invention relates to a cosmetic product or product aimed for application on the skin or on the teeth, which contains at least one carbohydrate, or an analog thereof, which constitutes a fragment, or an analog, of the carbohydrate part in a glycoprotein or a glycolipid and/or contain at least one nucleotide sugar.

Description: COSMETICAL PRODUCT The present invention relates to a cosmetic product or product aimed for application on skin or teeth, which contains at least one carbohydrate (or an analog thereof) which constitutes a fragment, or an analog, of the carbohydrate part in a glycoconjugate. It has been found that the oligosaccharide part of various glycoconjugates (especially glycolipids and glycoproteins) have a number of important functions in vivo (Biology of Carbohydrates, vol. 2, Ginsburg et al., Wiley, New York, 1984; The Glycoconjugates, vol. I-V, Academic Press, New York; S. Hakomori, Ann. Rev. Biochem. , vol. 50, pp. 733-64, Ann. Rev. Biochem. vol. 58, 309-350; Feizi, Nature, pp. 314, 1985; S. Hakomori, Chemistry and Physics of Lipids, vol 42, pp. 209- 33). Among other things it was found that - the carbohydrate structures are important for the stability, activity, localisation, immunogenicity and degradation of glycoproteins; - carbohydrates are antigenic determinants (for example blood group antigens) ; - carbohydrates function as receptors when bound to cell surfaces for pathogens, proteins, hormons, toxins and during cell-cell interactions; - carbohydrates are important for oncogenesis, since specific oligosaccharides have been found to be cancer-associated antigenic determinants; - frequently, only a smaller sequence (di- or trisaccharide) of the carbohydrate part of the glycoconjugate is required for full biological activity (e.g. receptor activity) . Universities and Industry are at present working intensely on developing the use of biologically active oligosaccharides within a number of different fields, such as - novel diagnostics and blood typing reagents - highly specific materials for affinity chromatography - cell-specific agglutination reagents - targetting of drugs - monoclonal antibodies, specific against e.g. cancer- associated structures - therapy - development of a new type of therapy, as an alternative to antibiotics, based on the inhibition of the attachment of bacteria and virus on cell surfaces with specific oligosaccharides - stimulation of the growth of plants and protection against pathogens. Besides the above mentioned areas, a considerable future market is envisaged for fine chemicals based on biologically active carbohydrates. About ten different monosaccharides are included in the carbohydrate part of the glycoconjugates: D-glucose (Glc) , D- galactose (Gal) , N-acetyl-D-glucosamine (GlcNAc) , N-acetyl- neuraminic acid (Neu5Ac) , D-mannose (Man) , L-fucose (Fuc) , N- acetyl-D-galactosamin (GalNAc) , xylose (Xyl) and arabinose (Ara) (the abbreviations in brackets are according to IUPAC- IUB's abridged terminology for monosaccharides, J.Biol.Chem. , vol 257, pp. 3347-3354, 1982, in which publication one also can find the nomenclature used in this text to describe oligosaccharide sequences) . The number of possible structures is almost infinitely great because both the anomeric configuration and the position of the O-glycosidic bond can be varied. The present invention describes a new type of cosmetic product or a product for application on the skin or on the teeth, which is characterized by that the product contains at least one carbohydrate, or ah analog thereof - which constitutes a fragment, or an analog, of the carbohydrate part in a glycoprotein or a glycolipid or a nucleotide sugar - beside one, several or all of the previously used ingredients in cosmetic products. The cosmetic product can be in many different forms, e.g. in the form of a plaster, a soap, a cleansing cream, a tooth paste, in liquid form (e.g. cleansing water) or as a lotion or a cream ( e.g. night or day cream) . The carbohydrate or carbohydrate derivative function e.g. as an inhibitor for bacterial attachment to the skin or the teeth, as a moisturizer, or as a nutritional supplement for the skin in the production of protecting, moisturizing carbohydrates. Examples of nucleotide sugars are UDP-Gal, CMP-NeuAc, UDP- GalNAc, GDP-Fuc, etc. These can be produced preferentially with biotechnological methods involving enzymes, e.g. CMP- sialate synthase and other enzymes for synthesis of nucleotide sugars. Examples of carbohydrate structures of glycoconjugates are found in the references on p. 1 and in the tables below. Of special interest are the minutest fragments - often di-, tri- or tetrasaccharides or analogs - of these structures, which are sufficient to transfer biological activity. Examples of interesting structures are blood group determinants, cancer-associated oligosaccharide structures and structures with bacterial receptor activity (see references on page l above) . Table 1. Examples of glycolipid carbohydrate structures. Gaiiglio Series Neu5Ac 2 - 3 Galβl - 3 GalNAcβl - 4 Galβl - 4Glcβ1 - 1Cer G GalNAcβl - 4 Gal β1 - 4 Glcβl - 1 Cer I 3 Neu5Acα2 - 8 Neu5Acα2 Glυbo Series GalNAcβl - 3 Galαl - 4 Galβl - 4 Glcβl - 1 Cer Globo LacLo Series Fucαl - 2 Galβl - 4 GlcNAcβl - 3 Galβl - 4 Glcβl - 1 Cer La Muco Series fucopenlaosylV GalNAcαl - 3 Galβl - 3 Galβl - 4 Glcβl - 1 Cer Gala Series Galαl - 4 Galβl - 1 Cer Galabi T a bl e 2 . Examples of carbohydrate structures (N- and O -bound, respectively) in glycoproteins. N-Bound Oligoiiiaiuiositlic Type Manαl -2 Manαl - 2 Manαl I 6 Man l 13 16 Man ol - 2 Manαl Manβl - 4 GlcNAcβl - 4 GlcNAcβAsn Manαl - 2 Manαl Complex (N-aeelyUaeLosaiiiiiie) Type Neu5Acu2 - 6 Galβ 1 - 4 GlcNAcβl - 2 Manαl I 6 Manβl - 4 GlcNAcβl - 4 GlcNAcβAsπ 13 Neu5Acα2 - 6 Galβ 1 - 4 GlcNAcβl - 2 Manαl Hybrid Type Neu5Acα2 - 6 Gap 1 - 4 GicNAcβl - 2 Manαl 16 Neu5Acα2 - 6 Galβ 1 - 4 GlcNAcβl - 2 Manαl Manβl - 4 GlcNAcβl - 4 GlcNAcβ 14 13 Man l 12 Neu5Ac 2 - 3 Galβ 1 - 4 GicNAcβl O-Bounr. Neu5Acα2 I 6 Neu5Acα2 - 3 Galβl - 3 GalNAcαThr/Ser GalNAcαl - 3(Galβ1 - 4GlcNAcβ1 - 3)„Galβ1 I 3 GalNAcαThr/Se 16 Fucαl - 2 Galβl - 4GlcNAcβ1 Table 3. Example of human blood group structures. Blood group SLrucLure A GalNAcαl - 3GalBl- Fuc ' 1 B Galαl -3Galβ1- Fucαl H Fucαl -2GalB1- Le a GalBl - 3GlcNAc- Fucα e b GalBl - 3GlcNAc Fucαl Fucαl P 1 Galαl - 4Galβ1 - 4GlcNAcβ1 - 3GalB I - 4GIc P GalNAcβl - 3Galα1 - 4Galβ1 - 4Glcβ1- pk Galαl - 4Galα1 - 4Glcβ1- p Galβl -4GIcB1- Table 4. Examples of cancer-associated carbohydrate antigen. Galαl -4 Galβl -4 Glcβ Galβl -4(Fucα1 - 3)GlcNAc [Galβl -4(Fucα1 -3)GIcNAcβ1 -3] 3 Galβ Galβl -3 GalNAcα GalNAcαl - 3 GalNAcβ1-Hex. GalNAcαl - 3 Hex-HexNAc. Neu5Acα2 - 8 Neu5Acα2 - 3 Gal β1 - 4 Glc Neu5Acα2 - 3 Galβl - 3(Fucα1 - 4)GlcNAc The carbohydrate is produced according to the invention preferentially by biotechnological methods employing glycosidase and/or glycosyltransferase. Both hydrolases (glycosidases, EC 3.2) and glycosyl¬ transferases (EC 2.4) can be used for synthesis (glycosidases: see Nisizawa et al, in "The Carbohydrates, Chemistry and Biochemistry", 2nd ed. , vol IIA, pp. 242-290, Academic Press, New York, 1970) . With glycosidases reversed hydrolysis (equilibrium reaction) or transglycosylation (kinetic reaction) are often used to obtain synthesis (see e.g. K.G.I. Nilsson, Carbohydr. Res., vol. 167, pp. 95-103, 1987, Trends in Biotechnology., vol. 6, pp. 256-264, 1988). EH Reversed hydrolysis: DOH + HOA DOA + H j O -ROH +HOA Transglycosylation : DOR + EH E-D DOA + EH H 2 0 DOH + EH (DOH is donor saccharide, DOR is donor glycoside wijth - or β- glycosidically bound aglycon (=R) , HOA is acceptor saccharide and EH is enzyme) . With transferases, a nucleotide sugar (UDP-Gal, CMP-Sia, UDP- GalNAc, GDP-Fuc, etc) , which is relatively expensive, is used as donor. Furthermore, glycosidases are abundant and can often be used directly without purification. A disadvantage is however that relatively low yields and the wrong product isomers often are obtained.

Claims: CLAIMS 1. Cosmetic product or a product for application on the skin or on the teeth, which contains one, several or all of the in cosmetic products previously used ingredients, characterized in that the product also contains at least one carbohydrate - or an analog thereof - which constitutes a fragment, or an analog, of the carbohydrate part in a glycoprotein or a glycolipid and/or at least one nucleotide sugar. 2. Product according to claim 1, characterized in that the carbohydrate or the nucleotide sugar is produced by a biotechnological method employing glycosidase, glycosyltransferase and/or CMP-sialate synthase or another nucleotide sugar synthesising enzyme.

Inventors: NILSSON KURT, NILSSON, KURT
Applicants: PROCUR AB
Application year: 1991
Main classification: A61K7
IPC codes: A61K8, A61Q11, A61Q19