Preparation method of temperature and pH sensitive shell cross-linked polymeric micelle
A cross-linked polymer and sensitive technology, which is applied in the direction of non-active ingredient medical preparations, drug combinations, pharmaceutical formulations, etc., can solve the problem of strict polymer block ratio, uneven micelle size, and low critical Concentration and other issues, to achieve excellent drug loading performance, easy operation, good environmental protection and stability
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[0025] Example 1
[0026] The first step of synthesis: Dissolve 3.6g of N-3-aminopropyl methacrylamide hydrochloride monomer in 8ml of deionized water, adjust the pH to 4~5 and freeze, then 0.06g 4-cyano-4 -(Thiobenzoyl)pentanoic acid and 0.015g 4,4'-azo-(4-cyanovaleric acid) are dissolved in 0.5ml dioxane solvent, and the two are mixed in a single-neck bottle, single-neck bottle It contains a rotor and is connected to a glass tee to completely remove air and put the solution in a nitrogen-protected environment. The oil bath is heated to 70°C for 16 hours to react, and the resulting mixture is placed in an aqueous solution with pH=4~5 After dialysis for three days, it was freeze-dried to obtain poly(N-3-aminopropylmethacrylamide hydrochloride) polymer.
[0027] The second step of synthesis: take 0.27 g of poly(N-3-aminopropyl methacrylamide hydrochloride) as a macromolecular chain transfer agent and place it in a single-neck bottle containing a rotor, and add 1.5 mg of 4,4'-couple...
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[0031] Example 2
[0032] Same as Example 1, but the amount of 4,4'-azo-(4-cyanovaleric acid) in the first step of the synthesis is changed to 0.012g monomer (N-3-aminopropylmethacrylamide hydrochloric acid) in the system The molar ratio of salt) to chain transfer agent (4-cyano-4-(thiobenzoyl)pentanoic acid) and initiator (4,4'-azo-(4-cyanovaleric acid)) is 100:1:0.2.
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[0033] Example 3
[0034] Same as Example 1, but in the first step of synthesis, the water solvent is changed to 15ml. The monomer (N-3-aminopropylmethacrylamide hydrochloride) and the chain transfer agent (4-cyano-4-( The molar ratio of thiobenzoyl)pentanoic acid) and initiator (4,4'-azo-(4-cyanovaleric acid)) is still 100:1:0.25.
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