A kind of nano drug loading system based on amino acid polymer and its preparation method and application
A nano-loaded drug and amino acid technology, which is applied in the direction of pharmaceutical formulations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problems of high moisture sensitivity and harsh polymerization conditions, and achieve short reaction cycles, The preparation method is simple and the effect is easy to achieve
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[0093] The present invention provides a kind of preparation method of polyamino acid, comprises the following steps:
[0094] (1) Under ice-water bath conditions, slowly drop a certain amount of thionyl chloride (drop rate 0.2-2mL / min) into a certain amount of anhydrous pyridine reaction flask and stir for 10-30min to obtain a mixed solution; , the volume ratio of thionyl chloride to anhydrous pyridine is 1:20~30;
[0095] (2) At a certain temperature, slowly add a certain amount of hydrophobic amino acid or its salt (taking phenylalanine as an example in the present invention) to the above-mentioned mixed solution, and continue to stir for a certain period of time to obtain polyphenylalanine (PPhe ); wherein, the molar ratio of thionyl chloride to phenylalanine (or its salt) is 0.5~6:1~2 (preferably 1:1~2, more preferably 1.2:1), and the reaction temperature is 0 ~55°C (preferably 25~40°C, more preferably 35°C), the reaction time is 0.5~24h (preferably 3h), the yield of the ...
Embodiment 1
[0100] The preparation of embodiment 1 polymer PPhe
[0101] 1, a kind of preparation method of polymer PPhe, comprises the following steps:
[0102] (1) Slowly add thionyl chloride dropwise (drop rate: 0.2-2mL / min) into the reaction flask filled with anhydrous pyridine and stir for 10-30min under ice-water bath conditions to obtain a mixed solution;
[0103] (2) Slowly add phenylalanine (the amino acid in this example is L-phenylalanine) to the above mixed solution, and continue to stir for 10 to 30 minutes to obtain polyphenylalanine (PPhe); wherein, the chlorinated The molar ratios of sulfoxide to phenylalanine are 2:1, 1:1, 1.2:1, 1:2, 2:1, 3:1, 4:1, 5:1, 6:1, and the reaction temperature At 35°C, react for 3h.
[0104] (3) Pour the obtained polyphenylalanine (PPhe) into water and stir to terminate the reaction, then place the product in a centrifuge tube and centrifuge at 3000-8000rpm to remove unreacted monomers and pyridine, repeat 3-4 After the second time, it was r...
Embodiment 2
[0111] The preparation of embodiment 2 polyphenylalanine nanoparticles
[0112] 1. The preparation process of polyphenylalanine nanoparticles comprises the following steps:
[0113] (1) Different polyphenylalanine PPhe prepared in Example 1 (this example uses PPhe prepared with a molar ratio of thionyl chloride to phenylalanine of 1.2:1) and surface stabilizer DSPE-PEG 2000 Dissolve in dimethyl sulfoxide (DMSO) respectively, and make 10mg / mL solutions respectively for later use;
[0114] (2) the polyphenylalanine PPhe of above-mentioned preparation and surface stabilizer DSPE-PEG2000 The solution is mixed according to a certain ratio and slowly added dropwise to the aqueous solution at a speed of 1000rpm. The complex self-assembles in the aqueous solution to form a nanosystem; among them, DSPE-PEG 2000 The mass of is 50% of the mass of PPhe;
[0115] (3) Gained nanoparticle solution is placed in the ultrafiltration tube of molecular weight cut off (MWCO=100kDa), 3000rpm ultr...
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