Degradable hydrogel under physiological conditions

A hydrogel which is biodegradable under physiological conditions, is characterized in that:

• said hydrogel comprises at least one backbone moiety and a crosslinking moiety, which contains biodegradable linkers capable of decomposition by intramolecular cyclization reaction, so that the hydrogel is degraded to water soluble, smaller molecular weight components;
• said biodegradable linkers include moieties which are biodegradable under physiological conditions, as well as reactive functional groups which can form covalent bonds with one or more reactive polymers;
• the moieties which are biodegradable under physiological conditions have the formula
• wherein X is selected from OH or —HN—R0;
• Y is selected from:
• (1) NRO;
• (2) C(RpRq);
• (3) O, with the proviso that X is not OH;
• (4) C(RpRq), when X is —HN—R0, R0 and Rp together with the atoms attached form a 4, 5 or 6-membered heterocyclic ring;
• Y1 is selected from
• (1) C(R3R4);
• (2) C(O) or C(S), with the proviso that A is not C(O), C(S), SO, or SO2;
• (3) O, S, SO or SO2 with the proviso that A and Y are not O;
• (4) —NRn;
• and
• (5) a bond;
• J1 is C (R10R11) or a covalent bond;
• the wavy line indicates the attachment point of an amide bond or an ester bond formed between a biodegradable linker and a biologically active substance or a reactive polymer;
• A and B together form a ring system, including aryl having from 6 to 15 carbon atoms;
• cycloalkyl having a 3, 4, 5, 6, 7, 8, 9, or 10 membered ring;
• cycloalkenyl having a 4, 5, 6, 7, 8, 9, or 10 membered ring;
• cycloalkynyl having a 5, 6, 7, 8, 9, or 10 membered ring;
• saturated and unsaturated monocyclic, polycyclic and fused cyclic;
• saturated and unsaturated monoheterocyclic, polyheterocyclic and fused heterocyclic, containing one or more heteroatoms N, S or O in each heterocyclic ring thereof and each ring being from 3- to 10-membered;
• each of aforementioned ring is optionally substituted with one or more groups selected from lower alkyl, lower alkoxy, acyl, acyloxy, alkoxycarbonyl, aryl, phenyl, benzyl, halo, haloformyl, haloloweralkyl, trifluoromethyl, trifluoromethoxy, trichloromethyl, cyanato, isocyano, isocyanate (or salt), isothiocyanate, thiocyanate (or salt), lower alkylthio, amino, imino, amino lower alkyl, lower alkylamino, lower dialkylamino, hydroxyl, hydroxyl alkyl, nitro, nitrile, isonitrile, pyridyl, azido, carboxyl, carboxamido, acetic acid, thiolalkyl, carbonate (or salt), carbamate, loweralkylcarbamyl, diloweralkylcarbamyl, sulfonic acid, sulfonamide, sulfonate (or salt), sulfonyl, sulfoxide, sulfide, disulfide, mercapto (or sulfhydryl);
• or A and B together with the atoms to which they are attached form an aromatic ring or a hetroaromatic ring optionally substituted by at least one group defined above;
• or A and B together with the atoms to which they are attached form a polyaromatic ring or a polyheteroaromatic ring optionally substituted by at least one group defined above;
• Y, A, B contains at least one reactive group which can form a covalent bond with a reactive polymer to connect to one or more reactive polymers;
• R0, RO, R3, R4, R10, R11, Rn, Rp, Rq are independently selected from hydrogen, lower alkyl, lower alkoxy, acyl, acyloxy, alkoxycarbonyl, aryl, phenyl, benzyl, halo, haloformyl, haloloweralkyl, trifluoromethyl, trifluoromethoxy, trichloromethyl, cyanato, isocyano, isocyanate (or salt), isothiocyanate, thiocyanate (or salt), lower alkylthio, amino, imino, amino lower alkyl, lower alkylamino, lower dialkylamino, hydroxyl, hydroxyl alkyl, nitro, nitrile, isonitrile, pyridyl, azido, carboxyl, carboxamido, acetic acid, thiolalkyl, carbonate (or salt), carbamate, loweralkylcarbamyl, diloweralkylcarbamyl, sulfonic acid, sulfonamide, sulfonate (or salt), sulfonyl, sulfoxide, sulfide, disulfide, mercapto (or sulfhydryl);
• or R0, RO, R3, R4, R10, R11, Rn, Rp, Rq are independently selected from —SO2—OH, —SO2—NRm1Rm2, —SO2—Rm3, —O—Rm4, —S—Rm5, —N—Rm6Rm7, —C(O)Rm8, —C(O)ORm9, —OC(O)Rm10, —NHC(O)Rm11, —C(O)NRm12Rm13, —NHC(O)NRm14Rm15, wherein Rm1, Rm2, Rm3, Rm4, Rm5, Rm6, Rm7, Rm8, Rm9, Rm10, Rm11, Rm12, Rm13, Rm14, and Rm15 are independently selected from hydrogen (H), (C1-C18) alkyl, aryl, (C1-C18 alkyl)OH, (C1-C18 alkyl)SH, (C1-C18 alkyl)COOH, C1-C18 alkyl)NH2, (C0-C4 alkyl)(C5-C6 cycloalkyl), (C0-C10 alkyl)(C5-C6 heterocyclic), (C0-C4 alkyl)(C6-C10 aryl), (C0-C4 alkyl)(C4-C9 heteroaryl);
• or Rp and Rq are independently selected from (C1-C20) alkyl, (C1-C10 alkyl)OH, (C1-C10 alkyl)SH, (C2-C3 alkyl)SCH3, (C1-C4 alkyl)CONH2, (C1-C10 alkyl)COOH, (C1-C10 alkyl)NH2, (C1-C4 alkyl)NHC(NH2+)NH2, (C0-C4 alkyl)(C3-C6 cycloalkyl), (C0-C4 alkyl)(C2-C5 heterocyclic), (C0-C4 alkyl)(C6-C10 aryl), (C0-C4 alkyl)(C6-C10 aryl)R16, (C1-C4 alkyl)(C3-C9 heteroaryl), and C1-C12 alkyl(W1)C1-C12 alkyl, wherein W1 is a heteroatom selected from N, S and O;
• R16 is selected from H, OH, halo, C1-C7 alkyl, C2-C7 alkenyl, C2-C7 alkenyl, CO2H, CO2(C1-C7 alkyl), NH(C0-C10 alkyl), O(C1-C10 alkyl), aryl, and heteroaryl.