Thermosensitive polyphosphazene-bioactive molecule conjugates, preparation method thereof and use thereof

A poly(organophosphazene)-bioactive molecule conjugate in which a biodegradable and thermosensitive poly(organophosphazene) with a functional group represented by the following Chemical Formula 1 and a bioactive molecule represented by the following substituent R10 are combined:

• wherein,
• p is an integer between 7 and 50,
• R1 is selected from the group consisting of H, HCH2, CH3, CH2SH, CH(CH3)2, CH2CH(CH3)2, CH(CH3)C2H5, CH2CH2SCH3, CH2C6H5, CH2C6H4OH, CH2C2NH2C6H4, OCOC4N+H9, CO2C2H5, CH2CO2C2H5, (CH2)2CO2C2H5, and HCONHCH(CH2C6H5),
• R2 is selected from the group consisting of CH3, C3H7, C4H9, C2H5, CH2C6H5, and CH2CHCH2,
• R3 is CH(W),
• R4 is selected from the group consisting of CO2, CO2CH2CO2, CO2CH(CH3)CO2, and CONHCH(X)CO2,
• R5 is selected from the group consisting of H, CH3, and C2H5,
• W and X are independently selected from the group consisting of H, HCH2, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)C2H5, CH2CH2SCH3, CH2C6H5, CH2C2NH2C6H4, OCOC4N+H9, CO2C2H5, (CH2)2CO2C2H5, CH2OH, CH(CH3)OH, CH2C6H4OH, CH2COOH, CH2CH2COOH, CH2CONH2, C4H8NH2, C3H6NHC(═NH)NH2, CH2C3N2H3, and CH2SH,
• R6 is CH(Y),
• R7 is selected from the group consisting of C2H4, C3H6, C4H8, CH2C6H4, O, CONHCH(Z)O, CO, S, CONHCH(Z)S, N, CONHCH(Z)N, CON, COCHNH(Z)CON, and CONHCH(Z)CO,
• R8 is selected from the group consisting of OH, SH, H, CH3, C2H5, C3H7, C4H9, CH2C6H5, CH2CHCH2, and protecting groups as defined in Table 1 described in the detailed description of the present application,
• Y and Z are independently selected from the group consisting of H, HCH2, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)C2H5, CH2CH2SCH3, CH2C6H5, CH2C2NH2C6H4, OCOC4N+H9, CH2OH, CH(CH3)OH, CH2C6H4OH, CH2COOH, CH2CH2COOH, CH2CONH2, C4H8NH2, C3H6NHC(═NH)NH2, CH2C3N2H3, and CH2SH,
• 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)rH, [NHCH(C4H8NH2)CO]rOH, [NHCH[(CH2)3C(═NH)(NH2)]CO]rOH, and protamines,
• q is an integer between 1 and 20,
• r is an integer between 1 and 18000,
• R10 is selected from the group consisting of paclitaxel, doxorubicin, camptothecin, epirubicine, 5-fluorouracil, 10-hydroxycamptothecin, 10-aminocamptothecin, 7-ethylcamptothecin, irinotecan, methotrexate, mitomycin C, taxoid, docetaxel, chlorambucil, calicheamicin, maytansinoid, 2-pyrrolino-doxorubicin (AN-201), daunorubicin, butyric acid, melphalan, 4′-dimethyldeoxypodophyllotoxin, curcumin, podophyllotoxin, epipodophyllotoxin, 4-β-amino-4′-O-demethylepipodophyllotoxin, tallysomycin S10b, daunomycin, duocarmycin A, duocarmycin SA, cis-aconityl-daunomycin, calicheamicin, diazeniumdiolate, netropsin, 6-metcaptopurine, glucuronidation, phosmidosine, streptonigrin, hematoporphyrin, desferrioxamine (DFO), deferiprone, acivicin, estramustine, enediyne, arginine-glycin-aspatic acid peptide, neuropeptides, albumin, Bovin serum albumin (BSA), bovin pancreatic ribonuclease (RNase A), Bovin seminal ribonuclease (BS-RNase), Bowman-birk protease inhibitor (BBI), collagen, fibronetin, laminin, erythropoietin (EPO), interferon, hirudin, colony stimulating factor (CSF), insulin, desmopressin, glucagon-like peptide 1(GLP1), human growth hormone antagonist, tumor necrosis factor receptor 1(TNFR1), asparaginase, adenosine deaminase, transforming growth factor-beta(TGF-beta), bone morphogenetic proteins (BMPs), growth factors, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), cytokines, theanine dexamethason, heparin, chitosan, hyaluronan, cyclodextran, starch, carbohydrate, saccharide, fluorescent protein (such as green fluorescent protein(GFP), red fluorescent protein (RFP)), virus-like particle (VLP), and vaccine,
• a, b, c, d, e, and f respectively represent the content of each substituent, wherein a, b, d, and f are independently from 0.01 to 1.9, c and e are independently from 0 to 1.9, and a+b+c+d+e+f=2.0, and
• n is from 5 to 100000.