Docetaxel polymeric micelle medicine composition taking amino acid as stabilizing agent
A technology of docetaxel and polymer glue, which can be used in drug combination, drug delivery, antitumor drugs, etc., and can solve the problems that have not been seen before.
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Embodiment 1
[0075] The synthesis of embodiment 1 amphiphilic block copolymer mPEG-PDLLA
[0076] Weigh 16g of methyl polyethylene glycol and 24g of lactide, put them in a closed reactor, add 50mg of stannous octoate, heat up to 120-140°C under nitrogen flow to melt the solid, and raise the temperature to 150-180°C °C for 6 hours. After cooling, a white solid crude product was obtained. After the crude product was dissolved in 1ml of dichloromethane, it was added into 100ml of diethyl ether under stirring, filtered, washed with diethyl ether three times, and the product was vacuum-dried for 24 hours.
[0077] In the NMR spectrum of the product (D-chloroform as a solvent), the mass ratio and molecular weight of methyl polyethylene glycol and polylactic acid in the polymer were confirmed by the peak area ratio of 5.2 ppm (PLA) and 3.6 ppm (PEG).
Embodiment 2
[0078] The preparation of embodiment 2 docetaxel polymer micelles
[0079] Pipette 10ml of 50mg / ml polymer acetonitrile solution into an eggplant-shaped bottle, add 10ml of 5mg / ml docetaxel acetonitrile solution, place the eggplant-shaped bottle on a rotary evaporator, reduce pressure (-0.1MPa), and water bath temperature 50 ℃, rotation speed 20 rpm, rotary evaporation for 30 minutes, add 50ml 0.2mg / ml arginine aqueous solution and rotary hydration for 1 minute, remove the eggplant-shaped bottle, vortex in a vortex for 1 minute, and filter the obtained solution through 0.22μm Membrane filtration, the filtrate was packed in 10ml vials, 2ml per vial, and immediately freeze-dried to obtain a white solid.
Embodiment 3
[0080] Preparation and stability investigation of embodiment 3 paclitaxel polymer micelles
[0081] Pipette 6ml of 50mg / ml polymer acetonitrile solution into an eggplant-shaped bottle, add 6ml of 10mg / ml paclitaxel acetonitrile solution, place the eggplant-shaped bottle on a rotary evaporator, reduce pressure (-0.1MPa), water bath temperature 50°C, speed 20 RPM, rotary evaporation for 30 minutes, add 25ml 0.2mg / ml aspartic acid aqueous solution and rotate for hydration for 1 minute, remove the eggplant-shaped bottle, vortex for 1 minute in a vortex instrument, and filter the obtained solution through a 0.22μm filter membrane, Packed in 10ml vials, 2.5ml per vial, freeze-dried immediately to obtain a white solid. Solid plus 0.9% sodium chloride injection or 5% glucose injection 5ml compounded to prepare a clear and transparent paclitaxel polymer micelle solution with slightly light blue opalescence. The obtained micellar solution was left still at 25 degrees Celsius for 24 hou...
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