| 主权项 |
1. A pharmaceutical dosage form for oral administration comprising a sanglifehrin as active ingredient in which the sanglifehrin active ingredient is protected by provision of a layer of enteric coat, said enteric coat being stable in the acid environment of the stomach, and adapted to release the active ingredient in the higher pH environment of the small intestine, wherein the sanglifehrin is a compound of formula (I) or a pharmaceutically acceptable salt thereof:wherein:
the moiety X1 represents —OR1, —NR1R2 or R3; R1, R2 and R3 independently represent alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkylcycloalkyl, alkylcycloalkenyl, alkenylcycloalkyl, alkenylcycloalkenyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, alkenylaryl or alkenylheteroaryl any of which groups may optionally be substituted by monocylic aryl or monocyclic heteroaryl; and wherein one or more carbon atoms of R1, R2 and R3 not being part of an aryl or heteroaryl group are optionally replaced by a heteroatom selected from O, N and S(O)p in which p represents 0, 1 or 2 and wherein one or more carbon atoms of R1, R2 and R3 are optionally replaced by carbonyl; or R1 and R2 are linked such that NR1R2 represents a saturated or unsaturated heterocyclic ring containing the specified nitrogen atom and wherein one or more carbon atoms of said ring are optionally replaced by a further heteroatom selected from O, N and S(O)p in which p represents 0, 1 or 2 and wherein one or more carbon atoms of said ring are optionally replaced by carbonyl and which heterocyclic ring may optionally be fused to an aryl or heteroaryl ring; and wherein one or more carbon atoms of an R1, R2 and R3 group may optionally be substituted by one or more halogen atoms; or R1 and/or R2 represents hydrogen; R9 represents H or OH; n represents a single or double bond, save that when n represents a double bond R9 represents H; R4, R5, R6, R7 and R8 independently represent H, F, Cl, Br, alkenyl or alkyl wherein one or more carbon atoms of said alkyl group are optionally replaced by a heteroatom selected from O, N and S(O)p in which p represents 0, 1 or 2 and wherein one or more carbon atoms of said alkyl group are optionally replaced by carbonyl and which alkyl group may optionally be substituted by one or more halogen atoms; X2, X3, X4, X5 and X6 independently represent C or N, and in the case of any of these groups representing N the attached substituent is absent; with the proviso that where R4, R6, R7 and R8 all represent H and X2, X3, X4, X5 and X6 all represent C, then R5 cannot represent OH, —Oalkyl or —O(CO)alkyl; including any tautomer thereof; and including a methanol adduct thereof in which a ketal is formed by the combination of the C-53 keto and the C-15 hydroxyl group and methanol. |
