A hybrid gel of polylactic acid microspheres and cross-linked hyaluronic acid for injection and its preparation method
A technology for cross-linking hyaluronic acid and polylactic acid microspheres, applied in the field of medicine, can solve the problems of not being able to achieve long-term beauty, the preparation process is cumbersome, and the treatment effect is not obvious, and can reduce the amount of solvent cross-linked hyaluronic acid or its Effects of the use of salt, strengthening of the internal structure of the skin, ease of control of the conditions of the preparation process
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[0017] The invention relates to a mixed gel of polylactic acid microspheres and cross-linked hyaluronic acid for injection and a preparation method thereof.
[0018] A hybrid gel of polylactic acid microspheres and cross-linked hyaluronic acid for injection, consisting of a salt solution of polylactic acid microspheres and cross-linked hyaluronic acid gel; the molecular weight of the polylactic acid microspheres is 15000-120000, and the average diameter is 10-150 μm, and the mass fraction in the mixed gel is 5-25%; the salt solution of the cross-linked hyaluronic acid gel is a cross-linked hyaluronic acid gel at an osmotic pressure of 250-350 mOsmol / L, It is obtained by swelling and balancing in sodium chloride solution or phosphate buffer solution with a pH of 6.5-7.5; the cross-linked hyaluronic acid gel is divinyl sulfone or glycidyl ether cross-linked hyaluronic acid gel.
[0019] The preferred mass fraction of polylactic acid microspheres in the mixed gel is 6-15%.
[00...
Embodiment 1
[0029] Add 5g of polylactic acid with a molecular weight of 15,000 to 150ml of dichloromethane and dissolve it. Dissolve another 2.5g of polyvinyl alcohol in 500ml of water and dissolve it in a water bath at 75°C. Add the polylactic acid solution dropwise to the aqueous solution of polyvinyl alcohol at a rate of 40 Drops per minute, after the dropwise addition was completed, the reaction was stirred for 2 hours, and the reaction temperature was 75°C. After the reaction was completed, dichloromethane was removed to obtain the reaction solution, and the reaction solution was filtered to collect the filter cake to obtain 4.8g of polylactic acid microspheres;
[0030] Dissolve 4g of hyaluronic acid (average molecular weight 1.6 million) in 160ml of 0.5N dilute sodium hydroxide solution, then add 1g of divinyl sulfone, and stir to obtain cross-linked hyaluronic acid;
[0031] Soak the cross-linked hyaluronic acid with a phosphate buffer solution with an osmotic pressure of 250mOsmol...
Embodiment 2
[0034] Add 5g of polylactic acid with a molecular weight of 120,000 to 175ml of dichloromethane and dissolve it. Dissolve another 7.5g of polyvinyl alcohol in 500ml of water and dissolve it in a water bath at 85°C. Add the polylactic acid solution dropwise to the aqueous solution of polyvinyl alcohol at a rate of 30 Drops per minute, after the dropwise addition was completed, the reaction was stirred for 4 hours, the reaction temperature was 85°C, and the methylene chloride was removed at the end of the reaction to obtain the reaction liquid, and the reaction liquid was filtered to collect the filter cake to obtain 4.9g of polylactic acid microspheres;
[0035] Dissolve 4g of hyaluronic acid (average molecular weight 2 million) in 140ml of 1.5N dilute sodium hydroxide solution, then add 2g of divinyl sulfone and stir to obtain cross-linked hyaluronic acid;
[0036] Soak the cross-linked hyaluronic acid with a phosphate buffer solution with an osmotic pressure of 350mOsmol / L and...
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