Biodegradable drug-polymer conjugate

A drug-polymer conjugate, which is a copolymer of (i) at least one monomer of Formula (I):

• where:
• X may be the same or different at each occurrence and represents a terminal functional group comprising an alkyne or an azide;
• R is selected from the group consisting of linear and branched hydrocarbons, optionally substituted aryl and optionally substituted heteroaryl;
• D is a releasable drug selected from prostaglandin analogues of formula (Xa):
• wherein:
• represents the point of attachment to L;
• represents a double or single bond;
• Y is optionally substituted C4 to C10 hydrocarbyl or optionally substituted C4 to C10 hydrocarbyloxy;
• R1 of formula (Xa) is hydroxy, C1 to C6 alkoxy, or C1 to C6 alkylamino;
• R9 and R11 are hydroxy;
• or
• D is a releasable drug selected from β-blockers of formula (XV):
• wherein:
• E is a bond or —OCH2—;
• R12 is hydrogen in the parent compound and is the linker L in formula I when the β-blocker is linked to the polymer backbone and is the alcohol residue (—O—) of an ester formed with an acid residue present in L or together with L forms a carbonate linking group;
• R13 and R14 are each independently selected from the group consisting of H and linear or branched C1-C4 alkyl optionally substituted by one or more substituents selected from the group consisting of hydroxy, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted amido, optionally substituted cycloalkyl, and optionally substituted aryl;
• and
• R15 of formula (XV) is an optionally substituted cycloalkyl or aryl moiety (including polycyclic moieties);
• L is a linker group;
• wherein the drug D is conjugated to the polymer backbone via an ester or carbonate linkage formed between the drug D and the linker group L;
• Q is independently selected at each occurrence and may be present or absent;
• wherein when present, Q represents a linking group and is selected from the group consisting of:
• wherein
• (R) indicates the end of the group attached to the group R and the opposite end is attached to (X);
• each of t and v are independently 0 or 1 and at least one of t and vis 1;
• R1, R1′, R2 and R2′ are independently selected from the group consisting of hydrogen, alkyl, alkoxy and alkoxyalkyl, and wherein one of the pairs of R1, R1′ and R2, R2′, may between the members of the pair form a carbocycle or heterocycle of 3 to 6 constituent ring members wherein the heterocycle may comprise from 1 to 3 constituent oxygen heteroatom ring members;
• and
• M is selected from the group consisting of a bond, optionally substituted C1 to C10 straight or branched chain aliphatic, the group —O—(C1 to C10 straight or branched chain aliphatic), an ether linking groups comprising C1 to C10 straight or branched chain aliphatic interrupted by a oxygen (—O—), the group —N(Rw)—(C1 to C10 straight or branched chain aliphatic) and an amine linking groups comprising C1 to C10 straight or branched chain aliphatic interrupted by the group N(Rw) wherein Rw is selected from hydrogen and C1 to C4 alkyl;
• q is 0 or 1;
• s is from 0 to 10;
• and
• (ii) at least one co-monomer of Formula (IIIa):
• wherein
• A may be the same or different at each occurrence and represents a group comprising a terminal functional group comprising an alkyne or an azide functionality, wherein the alkyne or azide functionality in the terminal functional group is complementary to the alkyne or azide functionality in a terminal functional group X present on a monomer of formula (I);
• J represents a bond, oxygen or linking functional group,
• Ra is selected from ethylene, propylene, butylene and mixtures thereof;
• m is 1 to 300;
• n is 3 to 8;
• B is a bond, oxygen, -MOC(O)N H)M′-, -MOC(O)OM′-, MC(O)NHM′-, or has a formula selected from formulae (VIa), (VIb), (VIc) and (VId):
• wherein M and M′ are independently selected from the group consisting of a bond, optionally substituted C1 to C10 straight or branched chain aliphatic, the group —O—(C1 to C10 straight or branched chain aliphatic), an ether linking group comprising C1 to C10 straight or branched chain aliphatic interrupted by a oxygen (—O—), the group —N(Rw)—(C1 to C10 straight or branched chain aliphatic) and amine linking groups comprising C1 to C10 straight or branched chain aliphatic interrupted by the group N(Rw) wherein Rw is selected from hydrogen and C1 to C4 alkyl;
• q is 0 or 1;
• and
• wherein in the monomers of formulae (VIa), (VIb), (VIc) and (VId), the groups R3, R3′, R4 and R4′ are independently selected from the group consisting of hydrogen, alkyl, alkoxy, alkoxy-alkyl, amino, alkyl amino, dialkylamino, amino-alkyl, alkylamino-alkyl, and dialkylamino-alkyl, wherein one of the pairs of R3, R3′, R4, R4′, may between the members of the pair form a carbocycle or heterocycle of 3 to 6 constituent ring members wherein the heterocycle may comprise from 1 to 3 constituent heteroatom ring members selected from oxygen and nitrogen which nitrogen may optionally be substituted by C1 to C6 alkyl;
• and
• wherein at least one of the groups Q in the monomer of formula (I) and B in the co-monomer of formula (IIIa) comprise at least one substituent selected from the group consisting of R1, R1′, R2, R2′, R3, R3′, R4 and R4′ which is present and is not hydrogen.