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Method for preparing injectable microgelparticles

A technology for injection and gel, which is applied in the field of preparation of injectable gel particles to achieve the effects of avoiding pollution, short time-consuming, and convenient replacement of dialysate

Inactive Publication Date: 2011-09-21
SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, since most of the cross-linking agents are cytotoxic, and the spatial network structure after cross-linking has a wrapping effect on the floating cross-linking agent, how to effectively, quickly and conveniently remove the cross-linking agent in the gel Rarely mentioned in current patents and studies

Method used

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  • Method for preparing injectable microgelparticles
  • Method for preparing injectable microgelparticles
  • Method for preparing injectable microgelparticles

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Dissolve 5.0 grams of hyaluronic acid dry powder with an average molecular weight of 1.2 million Daltons in 0.1M NaOH solution, stir at a speed of 90 rpm for 5 minutes, and configure a hyaluronic acid with a concentration of 10% (W / W) To the alkaline solution, 10.0 g of butanediol diglycidyl ether (BDDE) was added, stirred and placed in a thermostat at 40 degrees Celsius for 4 hours to form an alkaline cross-linked hyaluronic acid gel. Put the gel into a 1L cylindrical airtight container, use a peristaltic pump as the power, pass through PBS buffer at a speed of 60ml / min, and dialyze for 4 days. After the dialysis is completed, put it into a rotary chopper, add PBS buffer solution at a ratio of 1:1 by weight, and rotate at 8,000 to chop for 60 seconds. After chopping, the solution is centrifuged at 5,000 rpm for 30 minutes to remove the upper dispersion solution to obtain injectable gel particles. After testing, the concentration of the hyaluronic acid gel particles is...

Embodiment 2

[0023] Dissolve 5.0 grams of hyaluronic acid dry powder with an average molecular weight of 1.25 million Daltons in 0.125M NaOH solution, stir at a speed of 120 rpm for 4 minutes, and configure a hyaluronic acid with a concentration of 12.5% ​​(W / W) To the alkaline solution, 7.5 grams of butanediol diglycidyl ether (BDDE) was added, and after stirring, it was placed in a thermostat at 40 degrees Celsius for 5 hours to form an alkaline cross-linked hyaluronic acid gel. Put the gel into a 1L cylindrical airtight container, use a peristaltic pump as the power, pass through PBS buffer at a speed of 30ml / min, and dialyze for 5 days. After the dialysis is completed, put it into a rotary chopper, add PBS buffer solution at a ratio of 1:1 by weight, and rotate at 9,000 to chop for 60 seconds. After the minced solution is centrifuged at 8,000 rpm for 10 minutes, the upper dispersion solution is removed to obtain injectable gel particles. After testing, the concentration of the gel is ...

Embodiment 3

[0025] Dissolve 5.0 grams of hyaluronic acid dry powder with an average molecular weight of 1.1 million Daltons in 2.0M Na 2 CO 3 In the solution, stir at a speed of 60 rpm for 8 minutes, configure a hyaluronic acid alkaline solution with a concentration of 5.0% (W / W), add 0.5 g of divinyl sulfone (DVS), and put it in 35 degrees Celsius after stirring. After 4 hours in a constant temperature box, an alkaline cross-linked hyaluronic acid gel is formed. Put the gel into a 1L cylindrical airtight container, use a peristaltic pump as the power, pass through PBS buffer at a speed of 40ml / min, and dialyze for 5 days. After the dialysis is completed, put it into a rotary chopper, add PBS buffer solution at a ratio of 1:1 by weight, and rotate at 8,000 to chop for 60 seconds. After the minced solution is centrifuged at 10,000 rpm for 10 minutes, the upper dispersion solution is removed to obtain injectable gel particles. After testing, the gel concentration was 1.98 mg / ml, and the ...

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Abstract

The invention provides a method for preparing injectable microgelparticles, and the method comprises the following steps: adopting hyaluronic acid dry powder in accordance with standard requirements, carrying out cross-linking reaction to form water-insoluble cross-linking hyaluronic acid gel, carrying out postprocessing of dynamic dialysis, rotary crushing and centrifugal separation to form injectable microgelparticles. The method is safe and effective, and simple in processing flow, and can be used for adjusting the particle size of the microgelparticles by virtue of control on process parameters. The method has the advantages of good biocompatibility, internal anti-degradation capability, and suitability for subcutaneous filling, substituation of articular cavity lubricating fluid, conglutination prevention of internal wound and the like.

Description

technical field [0001] The invention relates to a preparation method of injectable gel particles. Background technique [0002] The hyaluronic acid gel modified by cross-linking overcomes the disadvantage of rapid degradation of uncross-linked hyaluronic acid gel, and has the advantages of good viscoelastic performance, insoluble in water, high mechanical strength and long degradation time. Its application range and performance are greatly improved, and the needs of clinical use can be better met. [0003] Cross-linked hyaluronic acid gel is generally formed by adding a cross-linking agent to a hyaluronic acid solution. Under certain conditions, the cross-linking agent and hyaluronic acid molecules are chemically bonded. Because of the chemical keying of the cross-linking agent, the original long-chain structure of hyaluronic acid is changed to form a spatial network structure. This structure improves the mechanical strength and viscoelasticity of the gel, thereby meeting ...

Claims

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Application Information

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IPC IPC(8): A61K47/36A61K9/00C08J3/24C08L5/08C08K5/1515C08K5/41
Inventor 朱彬蒋丽霞王文斌
Owner SHANGHAI QISHENG BIOLOGICAL PREPARATION CO LTD
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