Injection amphiphilic-microsphere-containing hyaluronic acid mixed gel and preparation method thereof

A technology of amphiphilic microspheres and hyaluronic acid, which is applied in the fields of medical science and prostheses, can solve the problems of difficult hyaluronic acid gel dispersion, poor hydrophilicity of polylactic acid microspheres, and non-hydrophilic polylactic acid, etc., to achieve The preparation process conditions are easy to control, the plasticity is good, and the effect is natural and gradual

Active Publication Date: 2015-12-09
IMEIK TECH DEV CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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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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  • Injection amphiphilic-microsphere-containing hyaluronic acid mixed gel and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] (1) Add 8 g of PLGA with a molecular weight of 120,000 and LA / GA=90 / 10 to 80 mL of dichloromethane to dissolve, and then add it dropwise to 160 mL of 2% polyvinyl alcohol aqueous solution at a rate of 50-60 Drops per minute, 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 5g of 25-45μm microspheres.

[0029] (2) Dissolve 0.4g of hyaluronic acid in 2mL of water for injection, add 0.2mL of 20% sodium hydroxide solution, add 15μL of 1,4-butanediol diglycidyl ether, add 4mL of 2.6mol / L hydrochloric acid to adjust When the pH is 6.5-7.5, 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 obtain 20 mL of a gel with a mass fraction of 20% hyaluronic acid .

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

Embodiment 2

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

[0033] (2) Dissolve 0.4g of hyaluronic acid in 2mL of water for injection, add 0.2mL of 20% sodium hydroxide solution, add 15μL of 1,4-butanediol diglycidyl ether, add 4mL of 2.6mol / L hydrochloric acid to adjust When the pH is 6.5-7.5, 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 obtain 20 mL of a gel with a mass...

Embodiment 3

[0036] (1) Add 20g of PLGA-PEG with a molecular weight of 100,000, in which PLGA has a molecular weight of 99,000, LA / GA=70 / 30. PEG has a molecular weight of 5,000, dissolve it in 200mL of dichloromethane, and then add it dropwise to 400mL with a mass fraction of 2% In the polyvinyl alcohol aqueous solution, the dropping rate is 50-60 drops / min. After the dropping is completed, stir at room temperature for 2 hours, raise the temperature to 45°C, remove the dichloromethane to obtain the reaction solution, filter the reaction solution to collect the filter cake, and sieve out 9g25 ~45 μm microspheres.

[0037](2) Dissolve 0.4g of hyaluronic acid in 2mL of water for injection, add 0.2mL of 20% sodium hydroxide solution, add 15μL of 1,4-butanediol diglycidyl ether, add 4mL of 2.6mol / L hydrochloric acid to adjust When the pH is 6.5-7.5, 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, ...

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Abstract

The invention relates to injection amphiphilic-microsphere-containing hyaluronic acid mixed gel and a preparation method thereof. The microsphere material relates to amphiphilic materials of PLLA-PEG, PLGA, PLGA-PEG and the like. The molecular weight of PLLA or PLGA is 10,000-500,000, the molecular weight of PEG is 1,000-10,000, and in PLGA, LA/GA=90/10-10/90. The average grain diameter of the microsphere is 1-200 [mu[m, and the mass percent of the microsphere in the gel is 1-50%; the gel is made from hyaluronic acid, divinyl sulphone crosslinked hyaluronic acid, or glycidyl ether crosslinked hyaluronic acid, the molecular weight of the hyaluronic acid is 100,000-3,000,000, and the mass percent of the hyaluronic acid is 1-50%. The gel can be also made from animal-derived collagen, chitosan, amino acid cellulose and sodium alginate. The microsphere mixed gel is prepared in a sodium chloride solution or a phosphate buffered solution with the osmotic pressure of 250-350 mOsm/L and pH of 6.5-7.5. According to the invention, the amphiphilic microsphere is directly mixed with hyaluronic acid gel, can be uniformly distributed in the gel easily, and is unlikely to aggregate into blocks in the water environment of a human body after being injected.

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 Applications(China)
IPC IPC(8): A61L27/26A61L27/50A61L27/52A61L27/54
Inventor 简军李亦晨
Owner IMEIK TECH DEV CO LTD
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