| abstract |
Biolabile prodrug compounds of the formula (1): PS-O-A-(CH2?)n?-B-D, wherein PS-O represents an alkoxide residue of any of the free hydroxy groups of a polysaccharide (PS-OH) compound with molecular weight (Mw?) of from 40,000 to 5,000,000 selected from dextran, carboxymethyl dextran, diethylaminoethyl dextran, starch, hydroxyethyl starch, alginates, glycogen, pullullan, agarose, cellulose, chitosan, chitin and carrageenan, A is a carbonyl group or absent, n is zero or a positive integer from 1 to 14, B is oxygen, a carbonyl group, NR wherein R is hydrogen or lower alkyl, or B is absent, and D is (i) a group of the formula (11?): R1?-CO-, wherein R1?-CO- represents the acyl residue of an anti-inflammatory carboxylic acid drug (R1?-COOH); or (ii) a group of the formula (12?): R2?-O-, wherein R2?-O- refers to the C-21 alkoxide residue of a known anti-inflammatory steroid (R2?-OH) or any other anti-inflammatory drug containing a hydroxy functional group; with the proviso that when A is absent, n is 0, and B is absent, then R1?-CO- is different from the acyl residue of acetylsalicylic acid; and non-toxic pharmaceutically acceptable acid addition or cation salts thereof. After oral administration of such prodrugs the parent drug is liberated selectively in the terminal ileum and the colon over an extended period of time. |