Process for the preparation of pharmaceutical compositions containing, as the active substance, at least 3S- 3R*(1R*,3S*,4S*)6S*,7E*,9S*,10S*,14R*,15E*,17E,19E,21R* ,23R*,26S*,27S*,34BR*- 9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34B- hexadecahydro-9,27-dihydroxy-3-2-(4-hydroxy-3- methoxycyclohexyl)-1-methylethyl-10, 21-dimethoxy-6,8, 12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido2,1- C1,4oxazacyclohentriacontino-1,5,11,28,29(4H,6H,31H)- pentone (rapamycin) and/or one of the derivatives thereof and/or pre-drugs thereof for inhibition of the rejection of organ or tissue transplants in mammals

摘要

The invention relates to the process for the preparation of pharmaceutical compositions to prevent the rejection of organ or organic tissue transplants in a mammal which needs said transplant, comprising the mixing of at least [3S-[3R*(1R*, 3S*, 4S*)] 6S*, 7E*, 9S*, 10S*, 14R*, 15E*, 17E, 19E, 21R*, 23R*, 26S*, 27S*, 34BR*]]-9, 10, 12, 13, 14, 21, 22, 23, 24, 25, 26, 27, 32, 33, 34, 34B-hexadeca- hydro-9,27-dihydroxy-3-[2-(4-hydroxy-3-methoxycyclo- hexyl)-1-methylethyl]-10, 21-dimethoxy-6,8, 12,14,20,26- hexamethyl-23,27-epoxy-3H-pyrido[2,1-C][1,4]oxazacyclo- hentriacontino-1,5,11,28,29(4H,6H,31H)pentone (rapamycin), of the formula IMAGE and/or one of the derivatives thereof and/or pre-drugs thereof, if necessary with one or more other chemotherapeutic agents which also act as inhibitors of the rejection of organ and tissue transplants, with pharmaceutically acceptable vehicular and/or auxiliary substances, in a proportion preferably between 0.01 and 15% by weight of active ingredient. The scope of the invention also embraces a process to prevent the rejection of organ or tissue transplants in a mammal, which involves the administration to said mammal of a) a quantity of rapamycin, in combination with b) a quantity of one or more other chemotherapeutic agents in order to inhibit the rejection of the transplant, for example azathioprine, corticosteroids, cyclosporin and FK506, the combined quantities of a) and b) being effective for inhibition of transplant rejection and maintenance of this inhibition.