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A preparation method and product thereof for 3D cross-linked hyaluronate gel for radiotherapy protection

A technology for cross-linking hyaluronic acid and hyaluronate, which is applied to medical preparations containing active ingredients, pharmaceutical formulas, aerosol delivery, etc., to achieve the effects of stable 3D structure, high cross-linking efficiency and reasonable reaction time

Active Publication Date: 2020-11-10
BLOOMAGE BIOTECHNOLOGY CORP LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] Aiming at the existing problems in the preparation of cross-linked hyaluronic acid gels, the advantages of less cross-linking agent consumption, convenient operation, moderate reaction time, no introduction of other organic reagents except cross-linking agents, good enzyme resistance, etc. , the present invention provides a method for preparing a 3D cross-linked hyaluronate gel with less cross-linking agent consumption, convenient operation and moderate reaction time

Method used

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  • A preparation method and product thereof for 3D cross-linked hyaluronate gel for radiotherapy protection
  • A preparation method and product thereof for 3D cross-linked hyaluronate gel for radiotherapy protection
  • A preparation method and product thereof for 3D cross-linked hyaluronate gel for radiotherapy protection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1 Preparation of cross-linked hyaluronic acid

[0033] Take 0.01 g of BDDE and mix with 5 mL of 1 wt% sodium hydroxide solution evenly, then add 1.0 g of sodium hyaluronate (3.5 million Da) and stir to dissolve evenly. The above reactants were sealed and left to react at 3 °C for 15 h, then at 50 °C for 3 h, and finally at 20 °C for 15 h. Cut the final reaction product into about 1 cm 3 The small cubes were placed in phosphate sodium chloride buffer and dialyzed, and the resulting gel block was granulated through a 60-mesh sieve to obtain a cross-linked hyaluronic acid gel with a content of 20 mg / mL. Autoclaved at 121°C for 8 min.

Embodiment 2

[0034] Example 2 Preparation of cross-linked hyaluronic acid

[0035] Except that the crosslinking agent is different (BDDE is replaced with carbodiimide), other reaction temperature and time are all the same as in Example 1. Finally, a cross-linked hyaluronic acid gel with a hyaluronic acid content of 20 mg / mL was prepared. Autoclaved at 121°C for 8 min.

Embodiment 3

[0042] Example 3 In vitro resistance to enzymatic hydrolysis of cross-linked hyaluronic acid

[0043] The gel obtained by one-step cross-linking in the comparative example is designated as gel A, the gel obtained by two-step cross-linking of "low temperature-high temperature" is designated as gel B, and the gel obtained by two-step cross-linking of "high temperature-low temperature" is designated as gel C; the hyaluronic acid gel obtained in Example 1 is marked as Gel D, the DVS cross-linked gel in Comparative Example 1 is marked as Gel E, and the carbodiimide cross-linked gel in Example 2 is marked as Gel F.

[0044] Weigh the appropriate amount of six samples of A, B, C, D, E, and F (the content of cross-linked hyaluronic acid is 0.5 g) into a vial, add 5 mL of 0.1 mol / L phosphate buffer (pH 7.0) and 5 mL of hyaluronidase solution (100 U / mL), mix well, place in a 37°C water bath for 24 h, and then boil at 100°C for 10 min to inactivate. Filter through a 0.45 μm microporous ...

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Abstract

The invention provides a preparation method of a 3D cross-linked hyaluronate gel for radiotherapy protection. The preparation method comprises the following steps: (1) allowing hyaluronate and a crosslinking agent to stand still in an alkaline solution for reaction at 0-10 DEG C for 0.5 to 20h to obtain a gel A; (2) allowing the gel A to stand still for reaction at 30-60 DEG C for 0.5-24h to obtain a gel B; (3) allowing the gel B to stand still for reaction at 10-40 DEG C for 0.5-20h, carrying out dialyzing and granulating to obtain the 3D cross-linked hyaluronate gel, wherein the content of cross-linked hyaluronic acid in the obtained gel is 10-50mg / ml. The 3D cross-linked hyaluronate gel prepared according to the method provided by the invention can be used for, but is not limited to, preparing a tumor radiotherapy isolation protective agent. The preparation method provided by the invention adopts three-step crosslinking of 'low temperature, high temperature and low temperature' to ensure that a crosslinking direction between hyaluronic acid molecules at each temperature is formed, multi-direction and multi-space crosslinking are realized, and the crosslinking efficiency is high;the prepared cross-linked hyaluronate gel has a stabler 3D structure, compact texture, better enzymolysis resistance, radiation resistance and high safety.

Description

technical field [0001] The invention belongs to the field of preparation of cross-linked hyaluronic acid, in particular to a preparation method of cross-linked hyaluronate gel. Background technique [0002] Hyaluronic acid (HA) is composed of (1→3)-2-acetylamino-2-deoxy-β-D-glucose-(1→4)-O-β-D-glucuronic acid disaccharide repeating unit The straight-chain polysaccharides are widely present in many connective tissues such as skin, eye vitreous body, cartilage and joint synovial fluid, and play physiological functions such as moisturizing, nutrition and repair. Hyaluronic acid has good physical and chemical properties and biocompatibility, so it is widely used in cosmetic plastic surgery, isolation protection, ophthalmic surgery, joint cavity injection, surgical protection and other fields. However, it is easily degraded by hyaluronidase in the body and has a short retention time in the body. To prolong its in vivo duration, hyaluronic acid is often cross-linked, making it m...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08J3/24B33Y70/00A61K9/06A61K31/728A61P39/00C08L5/08
CPCA61K9/0019A61K9/06A61K31/728B33Y70/00C08J3/24C08J2305/08
Inventor 郭学平栾贻宏刘建建张燕杨莹莹吴万福耿凤
Owner BLOOMAGE BIOTECHNOLOGY CORP LTD
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