High-molecular anti-tumor medicine for bonding vascular disrupting agent and immunomodulatory agent and preparation method thereof
A technology of vascular blockers and immunomodulators, which is applied in the direction of antineoplastic drugs, drug combinations, and pharmaceutical formulations, can solve the problems of easy recurrence, metastasis, and spread of tumors, drug resistance, and unsatisfactory clinical chemotherapy effects, and improve the efficacy of drugs Problems, inhibition of diffusion transfer, effects of stimulus sensitivity
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Embodiment 1
[0067] 1. Preparation of polyethylene glycol monomethyl ether-b-polylactide:
[0068] Take by weighing 1.0g (4.9mmol) norbornene lactide and 0.8g (0.16mmol) polyethylene glycol monomethyl ether (molecular weight is 5000) in the dry anaerobic ampoule that has baked three times, then in argon Add a catalytic amount of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) and 5.0 mL of refined dichloromethane under air protection, and react at room temperature for 48 hours. After the completion, the sedimentation was repeated three times with anhydrous ether, left to stand and centrifuged, and then vacuum-dried to obtain polyethylene glycol monomethyl ether-b-polylactide. Its structural characterization can be seen in the H NMR spectrum figure 1 , Molecular Weight Distribution Plot Figure 7(B), indicating that the polymer has been successfully synthesized.
[0069] 2. Preparation of polyethylene glycol monomethyl ether-b-polylactide containing carboxyl side groups:
[0070] Weigh 1.2g (...
Embodiment 2
[0080] Other experimental steps and experimental conditions are as in Example 1, except that the molar ratio of main chain norbornene lactide and polyethylene glycol monomethyl ether (molecular weight is 5000) is adjusted to 10:1; 20:1; 40:1, Polyethylene glycol monomethyl ether-b-polylactide block polymers with different molecular weights were prepared. Then, the polyethylene glycol monomethyl ether-b-polylactide block polymer was used for subsequent grafting of compretidine and imiquimod, and a drug similar to that of Example 1 was also obtained.
Embodiment 3
[0082] Other steps and experimental conditions are as in Example 1, except that the addition ratio of compretidine containing diphenylcyclooctyne functional group and imiquimod containing diphenylcyclooctyne functional group in the preparation process of polymer bonded drug Adjusted to 7:1; 7:2, the polymer-bonded drugs with different grafting ratios of the two drugs were prepared.
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