Hyaluronan conjugates with pharmaceutically active substances, methods and compositions

A method for manufacturing a hyaluronan conjugate, comprising reacting hyaluronan in solution or gel form with an anhydride reagent to provide a hyaluronan hemi-ester, and subsequently binding the hyaluronan hemi-ester to a pharmaceutically active compound to form a hyaluronan conjugate having free hemi-ester groups and the pharmaceutically active compound bound to the hyaluronan via hemi-ester groups, wherein the hemi-ester groups have the formula:

• (a) —C(O)—(CHR)n—(CH2)(m-n)—COO—, where n is 0 or 1, m=2-8, and R=alkyl, aryl, O-alkyl or O-aryl;
• (b) —C(O)—(CHR)n—(CH2)(p-1)—O—(CH2)q—COO—, where n is 0 or 1, p and q are individually 1-4, and R=alkyl, aryl, O-alkyl or O-aryl;
• (c) —C(O)—(CH2)m—COO—, where m is 2-8;
• (d) —C(O)—(CH2)p—O—(CH2)q—COO—, where p and q are both 1-4;
• or
• (e) —C(O)—(CH2)r—O—(CH2)s—O—(CH2)t—COO—, where r and t are 1-2 and s is 2.