| 摘要 |
#CMT# #/CMT# An oligonucleotide inhibitor of tyrosinase gene expression comprising a sequence of 15-25 nucleotides including a specific 21 nucleotide sequence (SEQ ID NO:1) which hybridizes to the human tyrosinase gene by Hoogsteen pairing to form a triple helix structure, is new. #CMT# : #/CMT# An oligonucleotide inhibitor of tyrosinase gene expression comprising a sequence of 15-25 nucleotides including a specific 21 nucleotide sequence (SEQ ID NO:1) which hybridizes to the human tyrosinase gene by Hoogsteen pairing to form a triple helix structure, is new. Independent claims are included for: (1) a cosmetic or dermatological composition comprising the oligonucleotide inhibitor; and (2) cosmetic process of treatment for depigmentation or to bleach the skin or hair, comprising application of the composition on pigmented zone of the skin or pilous of hair and optional repetition of the operation until the appearance of depigmented effect. 5'-C*TTC*TC*TC*TTTTTC*C*TTTTTC*-3' sequence (SEQ ID No. 1), where C* is a 5-methyl-cytosine #CMT#ACTIVITY : #/CMT# Dermatological. #CMT#MECHANISM OF ACTION : #/CMT# Tyrosinase expression inhibitor. The ability of the oligonucleotide to inhibit the expression of human tyrosinase was tested using reverse transcriptase polymerase chain reaction. The results showed that the LNA oligonucleotide exhibited an inhibition of 49%. #CMT#USE : #/CMT# The composition is used as cosmetic care and/or make-up product. The oligonucleotide is useful for the manufacturing of a drug for topical purpose for the treatment or for prevention of the diseases resulting from overexpression and over activity of tyrosinase, particularly for the treatment or the prevention of regional hyperpigmentations by melanocytory hyperactivity such as idiopathic melasmas, hyperpigmentations located by benign melanocytory hyperactivity and proliferation such as the pigmentary spots of senescence (senile lentigos), accidental hyperpigmentations such as photosensitization or post-organic cicatrisation and for the treatment of achromia such as vitiligo (all claimed). #CMT#BIOTECHNOLOGY : #/CMT# Preparation: No preparation method is given. Preferred Components: The oligonucleotide comprises 18-21 nucleotides or 21-25 nucleotides, preferably 21 nucleotides. The oligonucleotide is a chimerical oligonucleotide comprising at least a chemical modification on the sugar part, nucleobase part and/or internucleotidic skeleton. The oligonucleotide is LNA or PNA. The oligonucleotide comprises at least a modification in 2'-O-alkyl and 2'-O-fluoro derivatives on the sugar part of nucleoside, phosphorothioate or methylphosphonate derivatives on the level of the internucleotidic skeleton, derivatives in 5' and/or 3' of intercalating type reactive groups, preferably acridine, and derivatives the formation of a bridging with the target sequence, preferably psoralene and azide groups. The oligonucleotide is present in the composition at 0.00001-10 wt.%, preferably 0.0003-3 wt.%. Preferred Composition: The composition is present in a form suitable for a topical application in particular in the form of an aqueous, hydroalcoholic or oily solution, an oil-in-water or water-in-oil simple or multiple emulsions, an aqueous or oily gel, anhydrous liquid, paste or solid product, an aqueous or oily dispersion of solid particles e.g. polymeric nanospheres or nanocapsules or an aqueous dispersion of lipidic (non)ionic vesicles. The composition further comprises cosmetic active ingredients such as chemical or physical solar filters. #CMT#ADMINISTRATION : #/CMT# Administration of the inhibitor is topical. #CMT#EXAMPLE : #/CMT# The beta -cyanoethyldiisopropylphosphoramidites nucleoside derivative was used for the synthesis of oligonucleotide. The oligonucleotide was synthesized in automatic synthesizer. The oligonucleotide sequence was deprotected by treating with 33% of ammonia solution for 18 hours at 55[deg]C. The oligonucleotide was purified by precipitating with ethanol in the presence of sodium acetate. The obtained oligonucleotide was 5'-C*TTC*TC*TC*TTTTTC*C*TTTTTC*-3' (where C* is a 5-methyl-cytosine). |
