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A preparation method of poly-L-lactic acid and cross-linked hyaluronic acid composite gel for injection and the resulting product

A technology of cross-linked hyaluronic acid and poly-L-lactic acid, which can be used in pharmaceutical formulations, prostheses, drug delivery, etc., can solve the problems of uneven gel particles, prone to granuloma, and inability to mix particles, so as to shorten the time of mixing. Equal time, reduce subcutaneous nodules and granulomas, and improve product safety

Active Publication Date: 2022-03-29
BLOOMAGE BIOTECHNOLOGY CORP LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method requires a lower concentration of sodium hyaluronate solution (that is, the concentration of solution A is low, and the concentration of solution A is 1% to 15%) in the mixing process of microspheres. In this case, crosslinking obtains gel A large amount of cross-linking agent needs to be added, which will cause pressure on the later purification, and the residual cross-linking agent will cause harm to the human body; if the concentration of sodium hyaluronate solution is high, the solution will be too viscous, and the particles cannot be thoroughly mixed, resulting in Particles are uneven, so adverse reactions such as granuloma are prone to occur after implantation

Method used

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  • A preparation method of poly-L-lactic acid and cross-linked hyaluronic acid composite gel for injection and the resulting product
  • A preparation method of poly-L-lactic acid and cross-linked hyaluronic acid composite gel for injection and the resulting product
  • A preparation method of poly-L-lactic acid and cross-linked hyaluronic acid composite gel for injection and the resulting product

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] This example mainly investigates the effect of the ratio of total sodium hyaluronate and lactic acid solution added twice on the performance of poly-L-lactic acid for injection and cross-linked hyaluronic acid composite gel (composite gel for short, the same below). The method is as follows :

[0040] 1. Dissolve 5g of sodium hyaluronate in 500g of water, mix well, add 5g of L-lactic acid under stirring, ultrasonically disperse, mix evenly, and carry out vacuum freeze-drying at a temperature of -20~-30°C for 48 hours to obtain Hyaluronic acid-poly-L-lactic acid sponge complex.

[0041] 2. Take 20g, 25g, 50g of 0.5mmol / L lactic acid solution, add a cross-linking agent polyethylene glycol diglycidyl ether (molecular weight: 500), the cross-linking agent is 5% of the mass of sodium hyaluronate, stir well Add 10 g of the hyaluronic acid-poly-L-lactic acid spongy complex prepared above, mix for 0.5 h until uniform, then place in a water bath at 40°C for 2 h; then transfer t...

Embodiment 2

[0045] This example mainly investigates the influence of crosslinking temperature and crosslinking time on the properties of the composite gel. The preparation method is as follows:

[0046] 1, with embodiment 1.

[0047] 2. Take 25g of 0.5mmol / L lactic acid solution, add a cross-linking agent polyethylene glycol diglycidyl ether (molecular weight: 500), the cross-linking agent is 5% of the mass of sodium hyaluronate, stir well and add the above-mentioned prepared 10g hyaluronic acid-poly-L-lactic acid spongy compound, mixed for 0.5h until uniform, then the first cross-linking, and then changing the temperature for the second cross-linking. After the cross-linking is completed, the pH is adjusted to neutral, and the pH is dialyzed in a neutral phosphate buffer for 24 hours to obtain a composite gel. The content of sodium hyaluronate in the composite gel is 2%, and the content of poly-L-lactic acid is 2%. %.

[0048] The cross-linking conditions and the numbers of the obtaine...

Embodiment 3

[0052] This example mainly investigates the effect of the amount of cross-linking agent on the performance of the composite gel.

[0053] 1, with embodiment 1.

[0054] 2. Take 25g of 0.5mmol / L lactic acid solution, add cross-linking agent polyethylene glycol diglycidyl ether (molecular weight is 500), the cross-linking agent is respectively 1%, 2%, 5% of the mass of sodium hyaluronate, 10%, after stirring evenly, add 10g of the hyaluronic acid-polylactic acid spongy compound prepared above, mix for 0.5h until uniform, then put it in a water bath at 50°C for 2h; then transfer it to a water bath at 25°C for 24h . After the cross-linking is completed, the pH is adjusted to neutral, and the pH is dialyzed in a neutral phosphate buffer for 24 hours to obtain a composite gel. The content of sodium hyaluronate in the composite gel is 2%, and the content of poly-L-lactic acid is 2%. %.

[0055] The numbers of each composite gel are shown in Table 3 below.

[0056] table 3

[005...

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Abstract

The invention discloses a method for preparing a composite gel of L-lactic acid and cross-linked hyaluronic acid for injection and the resulting product. Hyaluronic acid or its salt and L-polylactic acid are first prepared into a spongy compound, and then the sponge The acidic cross-linking is carried out twice at different temperatures after the compound is dissolved to obtain the final product. The spongy compound is very easy to absorb water, which reduces the difficulty of mixing raw materials and shortens the time required for mixing. It can increase the concentration of hyaluronic acid in the solution, reduce the use of cross-linking agents, and reduce the acidity of hyaluronic acid. Environmental degradation improves safety. The L-lactic acid particles are locked inside the gel by cross-linking, which reduces the adverse reactions caused by particle aggregation, and reduces the accumulation and blockage of the needle site caused by the movement of the L-lactic acid particles between the gels during the injection process. Occurs, and the cross-linking under acidic conditions reduces the degradation of the poly-L-lactic acid, and better maintains the stability of the poly-L-lactic acid particles.

Description

technical field [0001] This field relates to a preparation method and the resulting product of a composite gel of L-lactic acid and cross-linked hyaluronic acid for injection, and specifically relates to a product with high safety, good stability, easy injection, and difficult displacement and accumulation of polylactic acid particles 1. The preparation method and the obtained product of poly-L-lactic acid and cross-linked hyaluronic acid composite gel for injection with few adverse reactions. Background technique [0002] Hyaluronic acid (Hyaluronic acid, HA) is a polymer polysaccharide composed of N-acetylglucosamine and D-glucuronic acid, which is widely found in animals and microorganisms, without species differences and immunogenicity. With high biological safety, it is a new type of biomedical material that has attracted much attention and has high medical value. [0003] In recent years, in microplastic surgery, soft tissue filler surgery has become more and more pop...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08J3/24C08J3/075C08L5/08C08L67/04A61L27/48A61L27/58
CPCC08J3/24C08J3/075A61L27/48A61L27/58A61L2400/06C08J2305/08C08J2467/04C08J2367/04C08J2405/08C08L5/08C08L67/04
Inventor 苏江伟吴万福张燕刘建建郭学平
Owner BLOOMAGE BIOTECHNOLOGY CORP LTD