Block copolymer for drug conjugates and pharmaceutical composition

1. A drug conjugated block copolymer in which a drug having a ketone structure being bound to a hydrazide group of the block copolymer, said block copolymer comprising a water-soluble polymer region consisting of polyethylene glycol and a polyamino acid region having a hydrazide group and a hydrophobic group in the side chain, wherein the block copolymer comprises the following structure:

wherein

R 1 , which may be the same or different, represents a hydrogen atom, a methoxy group, a methyl group, or a substituted linear or branched or cyclic C 1 -C 12 alkyl group, in which the substituent represents a functional group selected from the group consisting of a maleimide group, an amino group, a carboxyl group, a thiol group, a hydroxy group and an active ester group which may be protected,

R 2 represents a hydrogen atom, a saturated or an unsaturated C 1 -C 30 aliphatic carbonyl group or an arylcarbonyl group,

R 3 represents —O—R 5 or —NH—R 5 in which R 5 , which may be the same or different, represents a hydrophobic group, and R 4 represents a hydroxy group, a saturated or an unsaturated C 1 -C 30 aliphatic oxy group or an aryl-lower alkyloxy group,

L 1 and L 2 independently from each other represents a linker,

m represents an integer of 5-1000,

n represents an integer of 0-1000,

p represents an integer of 1-1000, and

q represents an integer of 1-1000,

provided that when units having a hydrophobic group in the side chain account for 25% or more 75% or less of the total units of the polyamino acids in the block copolymer and when units having a carboxylic acid group in the side chain are present, then the units having a carboxylic acid group in the side chain, units having a hydrophobic group in the side chain, and units having a hydrazide group in the side chain are randomly distributed throughout the polyamino acid region, and when units having a carboxylic acid group in the side chain are absent, then the units having a hydrophobic group in the side chain and units having a hydrazide group in the side chain are randomly distributed throughout the polyamino acid region, and

y represents an integer of 1 or 2, and wherein

as a result of said drug being bound to said block copolymer, the units having a hydrazide group in the side chain account for more than 0% to 35% or less of the total units of the polyamino acids in the block copolymer.

2. The drug-conjugated block copolymer according to claim 1 wherein R 5 is a hydrophobic group selected from the group consisting of a benzyl group, a phenyl group, a C 4 -phenyl group and a C 6 -C 16 alkyl group.

3. The drug-conjugated block copolymer according to claim 1 wherein the drug having a ketone structure is an anthracycline anti-cancer drug.

4. The drugs-conjugated block copolymer according to claim 3 wherein the anthracycline anti-cancer drug is bound at a number equal to 10% or more to 35% or less of the total units of the polyamino acids.

5. The drug-conjugated block copolymer according to claim 4 wherein the anthracycline anti-cancer drug is selected from the group consisting of doxorubicin hydrochloride, daunorubicin hydrochloride, epirubicin hydrochloride, pirarubicin, idarubicin hydrochloride, amrubicin hydrochloride, nemorubicin, and PNU-159682.

6. A polymeric micelle pharmaceutical composition formed by the drug-conjugated block copolymer according to claim 1 comprising a water-soluble polymer region consisting of said polyethylene glycol as the outer shell and an overall hydrophobic region consisting of said polyamino acids as the inner shell, said overall hydrophobic region having said hydrazide group-bound drug and said hydrophobic group, wherein said hydrazide group-bound drug and the hydrophobic group may be present in the overall hydrophobic region in the same block copolymer, or in the overall hydrophobic region in a different block copolymer.