Hyaluronic acid mixed gel containing amphiphilic microspheres for injection and preparation method thereof

A technology of amphiphilic microspheres and hyaluronic acid, which is applied in the field of hyaluronic acid mixed gel and its preparation, can solve the problems of uniform dispersion of hyaluronic acid gel, poor hydrophilicity of polylactic acid microspheres, and non-hydrophilicity of polylactic acid, etc. problem, to achieve the effect that the preparation process conditions are easy to control, the plasticity is good, and the effect is natural and gradual

Active Publication Date: 2017-11-10
IMEIK TECH DEV CO LTD
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  • Abstract
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Problems solved by technology

[0003] Chinese patent CN201410438010.3 discloses a mixed gel of polylactic acid microspheres and cross-linked hyaluronic acid for injection and its preparation method. It is easy to gather into lumps after the body, and it is difficult to disperse evenly in the hyaluronic acid gel
So polylactic acid is not an ideal injection filling material

Method used

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  • Hyaluronic acid mixed gel containing amphiphilic microspheres for injection and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] (1) Dissolve 8 g of PLGA with a molecular weight of 120,000 and LA / GA=90 / 10 in 80 mL of dichloromethane, and then add it dropwise to 160 mL of 2% polyvinyl alcohol aqueous solution at a rate of 50-60 drops / min, after the addition is complete, stir at room temperature for 1 hour, heat up to 45°C, remove dichloromethane to obtain a reaction solution, filter the reaction solution to collect the filter cake, and sieve out 5 g of microspheres of 25-45 μm.

[0029] (2) Dissolve 0.4 g of hyaluronic acid in 2 mL of water for injection, add 0.2 mL of 20% sodium hydroxide solution, add 15 μL of 1,4-butanediol diglycidyl ether, add 4 mL of 2.6 mol / L hydrochloric acid to adjust the pH to 6.5-7.5, then add 7 mL of 1% lidocaine hydrochloride, and then add 5 mL of PBS buffer solution to adjust the osmotic pressure to 250-350 mOsm / L to obtain a gel, and the mass fraction of hyaluronic acid is 20 mL of 20% gel.

[0030] (3) Add 5 g of PLGA microspheres prepared by the above method into...

Embodiment 2

[0032] (1) 10 g of PLLA-PEG with a molecular weight of 141,000, in which PLLA with a molecular weight of 140,000 and PEG with a molecular weight of 1,000, was dissolved in 100 mL of dichloromethane, and then added dropwise to 200 mL of 2% polyvinyl alcohol aqueous solution , the dropping rate is 50-60 drops / min, after the addition is completed, stir at room temperature for 1 hour, heat up to 45°C, remove dichloromethane to obtain the reaction solution, filter the reaction solution to collect the filter cake, and sieve out 6 g of 25-45 μm of microspheres.

[0033] (2) Dissolve 0.4 g of hyaluronic acid in 2 mL of water for injection, add 0.2 mL of 20% sodium hydroxide solution, add 15 μL of 1,4-butanediol diglycidyl ether, add 4 mL of 2.6 mol / L hydrochloric acid to adjust the pH to 6.5-7.5, then add 7 mL of 1% lidocaine hydrochloride, and then add 5 mL of PBS buffer solution to adjust the osmotic pressure to 250-350 mOsm / L to obtain a gel, and the mass fraction of hyaluronic aci...

Embodiment 3

[0036] (1) 20 g of PLGA-PEG with a molecular weight of 100,000, in which PLGA molecular weight is 99,000, LA / GA=70 / 30. PEG molecular weight is 5,000, is dissolved in 200 mL of dichloromethane, and then added dropwise to 400 mL of mass In the polyvinyl alcohol aqueous solution with a fraction of 2%, the dropping rate is 50-60 drops / min. After the dropping is completed, stir at room temperature for 2 hours, then raise the temperature to 45°C, remove the dichloromethane to obtain the reaction solution, filter the reaction solution to collect the filter cake, sieve 9 g of microspheres of 25-45 μm were separated.

[0037](2) Dissolve 0.4 g of hyaluronic acid in 2 mL of water for injection, add 0.2 mL of 20% sodium hydroxide solution, add 15 μL of 1,4-butanediol diglycidyl ether, add 4 mL of 2.6 mol / L hydrochloric acid to adjust the pH to 6.5-7.5, then add 7 mL of 1% lidocaine hydrochloride, and then add 5 mL of PBS buffer solution to adjust the osmotic pressure to 250-350 mOsm / L to...

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Abstract

The invention relates to a hyaluronic acid mixed gel containing amphiphilic microspheres for injection and a preparation method thereof. The microsphere material involves amphiphilic materials such as PLLA-PEG, PLGA, and PLGA-PEG. The molecular weight of PLLA or PLGA is 10,000-500,000, and that of PEG is 1,000-10,000. In PLGA, LA / GA=90 / 10-10 / 90. The average particle size of the microspheres is 1-200 μm, and the mass fraction in the gel is 1-50%; the gel component is hyaluronic acid, or hyaluronic acid cross-linked with divinyl sulfone or glycidyl ether, The molecular weight of hyaluronic acid is 100,000-3,000,000, and the mass fraction is 1-50%. The gel component can also be animal-derived collagen, chitosan, amino acid cellulose, sodium alginate, and the like. The microsphere mixed gel is prepared in a sodium chloride solution or a phosphate buffer solution with an osmotic pressure of 250-350 mOsm / L and a pH of 6.5-7.5. In the present invention, the amphiphilic microspheres are directly mixed with the hyaluronic acid gel, and the amphiphilic microspheres are easily and uniformly distributed in the gel, and after being injected into the human body, they are not easy to assemble into lumps in the water environment of the human body.

Description

technical field [0001] The invention relates to a hyaluronic acid mixed gel containing amphiphilic microspheres for injection and a preparation method thereof. Background technique [0002] In recent years, injectable gels for aesthetic medical purposes have developed rapidly. Injectable gels can achieve the cosmetic effect of minimally invasive treatment at the injection site, and have attracted widespread attention. However, the hyaluronic acid gel products currently on the market have a short degradation period, and it is difficult to guarantee medium and long-term effects. In order to achieve the above purpose, it is necessary to improve the added ingredients in the hyaluronic acid gel. Among them, artificial chemically synthesized polymer materials are more and more favored by the majority of beauty lovers because they reduce the risk of infection and are safe to use compared with animal-derived materials. However, artificially synthesized polymer materials should have...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/728A61L27/26A61L27/50A61L27/52A61L27/54
Inventor 简军李亦晨
Owner IMEIK TECH DEV CO LTD
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