Enhancement of activity and/or duration of action of soft...

A - Human Necessities – 61 – K

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A61K 31/56 (2006.01) A61P 27/02 (2006.01) A61P 27/14 (2006.01)

Patent

CA 2558944

Methods and compositions for enhancing the activity and/or duration of action of loteprednol etabonate and other soft anti-inflammatory steroids of the haloalkyl 17.alpha.-alkoxycarbonyloxy-11.beta.-hydroxyandrost-4-en-3-one- 17.beta.-carboxylate type and the corresponding .DELTA.1,4-compounds are described. The enhancing agents have the formula: (II) wherein R is H or C1-C4 alkyl; Z1 is carbonyl or .beta.-hydroxymethylene; X1 is -O- or -S-; R5 is -OH, -OR6, -OCOOR6 or -OCOR7 wherein R6 is C1-C4 alkyl and R7 is C1-C4 alkyl, fluoromethyl or chloromethyl; and the dotted line in ring A indicates that the 1,2-linkage is saturated or unsaturated; with the proviso that when R is C1-C4 alkyl, then R5 is -OH.

L'invention concerne des méthodes et des compositions d'amélioration de l'activité et/ou de la durée d'action de loteprednol etabonate et d'autres stéroïdes anti-inflammatoires doux du type haloalkyle 17a-alkoxycarbonyloxy-11.szlig.-hydroxyandrost-4-en-3-one-17.szlig.-carboxylate et les composés .DELTA.?1,4¿ correspondants. Les agents améliorant ont la formule (II) dans laquelle R représente H ou alkyle C¿1?-C¿4?; Z¿1? représente carbonyle ou .szlig.-hydroxyméthylène; X¿1? représente -O- ou -S-; R¿5? représente -OH, -OR¿6?, -OCOOR¿6? ou -OCOR¿7? où R¿6? représente alkyle C¿1?-C¿4? et R¿7? représente alkyle C¿1?-C¿4?, fluorométhyle ou chlorométhyle; et la ligne pointillée dans le cycle A indique que la liaison 1,2 est saturée ou insaturée, à la condition que lorsque R représente alkyle C¿1?-C¿4?, alors R¿5? représente -OH.

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