Penetrating topical pharmaceutical compositions containing 9-(2-hydroxyethoxymethyl) guanine

Claim 1

A composition of matter for topical administration, characterized in that it comprises: (a) from 0.01% to 10 % by weight of substituted purine antiviral of the formula wherein X is sulfur or oxygen, R11 is hydroxy, R 12 is amino, R 13 is hydrogen, a straight or branched chain or cyclic alkyl, hydroxyalkyl, benzyloxyalkyl or phenyl, R 14 is hydrogen, hydroxy or lower alkyl, R 15 is hydrogen, hydroxy amino, alkyl, hydroxyalkyl, benzoyloxy, benzoyloxy alkyl, benzyloxy, sulfamoyloxy, phosphate, carboxypropionyloxy, or acetoxy, R 16 is hydrogen, alkyl or hydroxyalkyl, or a pharmaceutically-acceptable salt thereof; (b) from 0.0 to 70% of ethanol or 2-propanol; (c) from about 0.01% to 99% by weight of a penetration-enhancing carrier consisting essentially of (i) a diol compound selected from the group consisting of 1,2 ethanediol, 1 ,2-propanediol, 1,3-propanediol, 1,2- butanediol, 1,3- butanediol, 1,4-butanediol, 2,3-butanediol, 2-ethoxyethanol, 2,2-oxy-bis-ethanol, glycerol monoacetate, and mixtures thereof, and (ii) a cell-envelope disordering compound of the formula R'-X where R' is a straight chain alkyl of about 7 to about 16 carbon atoms, a branched chain alkyl having from about 13 to about 22 carbon atoms, or a non-terminal alkenyl having from about 7 to about 22 carbon atoms, X is -OH. -COOH - C OOR 2 -COOC 2 H 4 OC 2 H 4 OH, -COOCH(CHOH) 4 CH 2 OH, -COOCH 2 CHOHCH 3 . -COOCH 2 CHOHCH 2 0H, -(OCH 2 CH 2 ) m OH, -SOCH 3 , or -P(OCH 3 ) 2 O, and R 2 is -H, -CH 3 , -C 2 H 5 , -C 3 H 7 , or -C 2 H 4 OH, R3 is -H, -CH 3 , -C 2 H 5 , -C 3 H 7 or C 2 H 4 OH, R 4 is -H, -CH 3 , -C 2 H 5 , -C 3 H 7 or-C 2 H 4 OH, R 5 is -H, -CH 3 , -C 2 H 5 , -C 3 H 7 or-C 2 H 4 OH, and m is an integer from 2-4; provided that when R' is an alkenyl and X is -OH, at least one double bond is in the cis-configuration; the ratio of diol compound: cell-envelope disordering compound being in the range of 1:1 to 500:1 by weight.