A polymer anti-tumor drug combined with angioblocker and immunomodulator and preparation method thereof
A vascular blocker, immunomodulator technology, applied in anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve the problems of unsatisfactory clinical chemotherapy effect, drug resistance, tumor recurrence, metastasis and spread, etc., to improve the efficacy and Effectiveness of drug utilization, improving therapeutic effect, reducing cytotoxicity
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Embodiment 1
[0067] 1. Preparation of polyethylene glycol monomethyl ether-b-polylactide:
[0068] Weigh 1.0 g (4.9 mmol) of norbornenyl lactide and 0.8 g (0.16 mmol) of polyethylene glycol monomethyl ether (molecular weight 5000) into a dry anaerobic ampoule that has been baked three times, and then place it under argon. Under gas protection, a catalytic amount of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) and 5.0 mL of purified dichloromethane were added, and the reaction was carried out at room temperature for 48 hours. After the end, use anhydrous ether to settle for three times repeatedly, stand for centrifugation and then vacuum dry to obtain polyethylene glycol monomethyl ether-b-polylactide. Its structural characterization is shown in the H NMR spectrum figure 1 , molecular weight distribution 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: ...
Embodiment 2
[0080] Other experimental steps and experimental conditions are as in Example 1, except that the molar ratio of main chain norbornenyl 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. The polyethylene glycol monomethyl ether-b-polylactide block polymer was then used for subsequent grafting of compretin 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 compretin containing diphenylcyclooctyne functional group and imiquimod containing diphenylcyclooctyne functional group in the preparation process of polymer-bonded drug Adjusted to 7:1; 7:2, to prepare the polymer-bonded drugs with different graft ratios of the two drugs.
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