Poly(organophosphazene) composition for biomaterials

A poly(organophosphazene) with a physiologically active substance covalently-bonded thereto, which is chemically-crosslinkable and has Chemical Formula 1 as follows:

• wherein,
• p is from 7 to 50,
• in NHCH(R1)CO2R2, R1 is selected from the group consisting of H, CH3, CH2SH, CH2OH, CH(CH3)2, CH2CH(CH3)2, CH(CH3)C2H5, CH2CH2SCH3, CH2C6H5, CH2C6H4OH, and CH2C2H2C6H4, and R2 is selected from the group consisting of CH3, C2H5, C3H7, C4H9, CH2C6H5 and CH2CHCH2
• in NH(R3)(R4)(R5), R3 is CH(W), R4 is selected from the group consisting of CO2, CONHCH(Q)CO2CO2, CH2CO2 and CO2CH(CH3)CO2, R5 is selected from the group consisting of H, CH3 and C2H5, in which each of W and Q is independently selected from the group consisting of H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)C2H5, CH2CH2SCH3, CH2C6H5, CH2C2NH2C6H4, CO2C2H5, (CH2)2CO2C2H5, CH2OH, CH(CH3)OH, CH2C6H4OH, CH2COOH, CH2CH2COOH, CH2CONH2, C4H8NH2, C3H6NHC(═NH)NH2, CH2C3N2H3, and CH2SH,
• in XR6, X represents N or O, and R6 is a compound that has a thiol group, a vinyl group, tyramine, tyrosine or a phenyl derivative, and is selected either from the group consisting of an acrylate compound, a methacrylate compound, an acrylamide compound, a vinyl sulfone compound, a thiol compound, a cysteine compound, a cisteamine compound, a mercaptic acid compound, an allyl pyrimidine compound and, a compound belonging to one of the foregoing compounds and having a thiol or vinyl group protected by a protecting group, or from the group consisting of a tyramine compound, a tyrosine compound, and a phenol derivative compound,
• NH(R7)(R8)(R9) represents a substituent having a functional group, in which R7 is CH(Y), R8 is selected from the group consisting of CH2, C2H4, C3H6, C4H8, CH2C6H4, CH2CO2, CH2OCOCH2CH2CO, CH2OCOCH2CH2CH2CO, CH2OCOCH2CH2CH2CH2CO, CH2CH2OCOCH2CH2CO, CH2CH2OCOCH2CH2CH2CO, CH2CH2OCOCH2CH2CH2CH2CO, O, CONHCH(Z)O, CONHCH(Z)CONHCH(M)O, CONHCH(Z)CONHCH(N)CONHCH(L)O, CO, CO2, S, CONHCH(Z)S, CONHCH(Z)CONHCH(M)S, CONHCH(Z)CONHCH(M)CONHCH(L)S, N, CONHCH(Z)N, CONHCH(Z)CONHCH(M)N, CONHCH(Z)CONHCH(M)CONHCH(L)N, CON, COCHNH(Z)CON, COCHNH(Z)CONHCH(M)CON, COCHNH(Z)CONHCH(M)CONHCH(L)CON, CONHCH(Z)CO, COCHNH(Z)CONHCH(M)CO, COCHNH(Z)CONHCH(M)CONHCH(L)CO, CONHCH(Z)CO2, COCHNH(Z)CONHCH(M)CO2, COCHNH(Z)CONHCH(M)CONHCH(L)CO2, [OCH(CH3)CO]q, (OCH2CO)q, [(OCH(CH3)CO]q, [OCO(CH2)8CO]q, [OCOC6H5O(CH2)3OC6H5CO]q and [OCOC6H6O(CH2)6OC6H6CO]q, and R9 is selected from the group consisting of OH, SH, H, NH2, CH3, C2H5, C3H7, C4H9, CH2C6H5, CH2CHCH2, NHCH(SH)CO2H, NH(CH2)qSH, NH(CH2CH2NH)qH, [NHCH(C4H8NH2)CO]qOH, [NHCH[(CH2)3C(═NH)(NH2)]CO]qOH, folic acid, hyaluronic acid, cyclodextrin, an imidazole compound, histidine, lysine, arginine, cysteine, thioalkyl amine, spermine, spermidine, TAT peptide, polyethyleneimine, polyhistidine, polylysine, polyarginine, heparin, chitosan, protamine, and a typical protecting group of a functional group, in which each of Y, Z, M, and L is independently selected from the group consisting of H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)C2H5, CH2CH2SCH3, CH2C6H5, CH2C2NH2C6H4, CO2C2H5, (CH2)2CO2C2H5, CH2OH, CH(CH3)OH, CH2C6H4OH, CH2COOH, CH2CH2COOH, CH2CONH2, C4H8NH2, C3H6NHC(═NH)NH2, CH2C3N2H3 and CH2SH, and q represents the number of the repeating unit ranging from 1 to 18000,
• R10 is a compound that has a thiol group, a vinyl group, tyramine, tyrosine or a phenyl derivative, and is selected either from the group consisting of an acrylate compound, a methacrylate compound, an acrylamide compound, a vinyl sulfone compound, a thiol compound, a cysteine compound, a cisteamine compound, a mercaptic acid compound, an allyl pyrimidine compound and, a compound belonging to one of the foregoing compounds and having a thiol or vinyl group protected by a protecting group, or from the group consisting of a tyramine compound, a tyrosine compound, and a phenyl derivative,
• R11 represents a physiologically active substance and is at least one selected from the group consisting of a protein, a polypeptide, a peptide, a fusion protein, an antibody, a hormone, a vaccine, a gene, an anticancer drug, and an angiogenesis inhibitor that have at least one functional group selected from the group consisting of a hydroxyl, an amide, an amino, a carboxyl, a thiol, a vinyl, an aldehyde, a halogen, and a ketone groups,
• a, b, c, d, e, f, g, h, and i represent a content of each substituent, in which a and b range from 0.01 to 1.9, respectively, c, d, e, f, g, h, and i range from 0 to 1.9, respectively, d and f cannot be simultaneously zero, and g, h, and i cannot be simultaneously zero, and a+b+c+d+e+f+g+h+i=2.0, and
• n represents a degree of polymerization of the poly(organophosphazene), ranging from 5 to 100000.