Polymethyl methacryate and crosslinking hyaluronic acid mixed gel for injection and preparation method thereof
A technology of polymethyl methacrylate and cross-linked hyaluronic acid, which is applied in the field of medicine, can solve the problems of long maintenance time and achieve the effects of long maintenance time, good plasticity and easy injection
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Embodiment 1
[0028] Using ethanol / water mixed solvent as the dispersion medium to prepare PMMA microspheres, refer to the method of literature (Hu Jie et al., Acta Polymerica Sinica, 2003, 4: 540-545), and change the conditions and ratio of polymerization to obtain suitable particle size. Dissolve 2.5g of polyvinylpyrrolidone (PVP) in 60ml of 55% ethanol solution, add 10g of methyl methacrylate, 1g of acrylic acid and 0.15g of azobisisobutyronitrile, blow nitrogen, pre-disperse for 30min, and raise the temperature to 70°C React for 50min, then lower the temperature to 55°C for 24h, finish the reaction, cool down to collect the dispersion, wash it repeatedly with ethanol / water, then centrifuge, and repeat the cycle 3 times, then use isotonic phosphate buffered saline (PBS) (each 1000ml contains NaH 2 .PO 4 2H 2 O 45 mg, Na 2 HPO 4 12H 2O 0.56g, NaCl 8.5g, pH 7.2) after soaking and washing repeatedly, centrifugal sedimentation to obtain microspheres with an average particle size ranging ...
Embodiment 2
[0040] Using the seed polymerization method, you can refer to the literature method (Sudol E D, El-Aasser M S, Vanderhoff J W.J PolymSci: Polym Chem, 1986, (24): 3499~3513), and appropriately change the conditions and proportions of the polymerization reaction to obtain the average particle size. PMMA microspheres with a diameter ranging from 10 to 30 μm. The microspheres were repeatedly washed with ethanol / water for more than 3 times, centrifugally settled, and then repeatedly soaked and washed with isotonic PBS, then centrifugally settled, and the obtained microspheres were used for future use.
[0041] Mix 10g of sodium hyaluronate (average molecular weight: 800,000 Daltons) with 70ml of 1% NaOH solution containing 0.5g of 1,4-butanediol diglycidyl ether, react at 50°C for 4h, and use deionized water at 70°C Purify at ℃ for 10 hours, extrude the gel to pass through a 60-mesh sieve, collect the gel particles, add an equal volume of PBS with 2 times the isotonic concentration...
Embodiment 3
[0051] Using the multi-step swelling polymerization method, you can refer to the literature method (Ckubo M, Shiozaki M, Tsujihiro M, FsukudaY. Colloid Polym Sci, 1991, (269): 222-226), and appropriately change the conditions and proportions of the polymerization reaction to obtain the average PMMA microspheres with a particle size range of 20-80 μm. The microspheres were repeatedly washed with ethanol / water for more than 3 times, centrifugally settled, and then repeatedly soaked and washed with isotonic PBS, then centrifugally settled, and the obtained microspheres were used for future use.
[0052] Mix 10g of sodium hyaluronate (average molecular weight: 520,000 Daltons) with 65ml of 1% NaOH solution containing 0.5g of 1,4-butanediol diglycidyl ether, react at 50°C for 4h, and use deionized water at 70°C Purify at ℃ for 10 hours, extrude the gel to pass through a 60-mesh sieve, collect the gel particles, add an equal volume of PBS with 2 times the isotonic concentration, and...
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