Preparation method of ectoin-hyaluronic acid composite gel and obtained product

A technology of hyaluronic acid and ectoine, applied in the fields of pharmaceutical formulation, pharmaceutical science, organic chemistry, etc., can solve the problems of complex cross-linked gel components, mixed types of cross-linked products, and difficult to control impurity content, etc. Improve immune protection, less impurities, mild conditions

Active Publication Date: 2021-03-12
BLOOMAGE BIOTECHNOLOGY CORP LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But this method mixes hyaluronic acid, ectoine and BDDE cross-linking agent to carry out cross-linking, and the two ends of BDDE are the structure of propylene oxide group, and reactivity is big, and the kind of cross-linking product is comparatively mixed, not only have experience BDDE cross-linked cross-linked hyaluronic acid, there are also BDDE cross-linked products with ectoine on both sides, and cross-linked hyaluronic acid branched with ectoine, etc.
The cross-linked gel obtained by this method has complex components, low grafting degree, poor controllability, difficult purification of cross-linking agent, poor biological safety, and difficult control of impurity content. It is only suitable for skin surfaces with relatively low safety requirements. cannot be used in vivo

Method used

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  • Preparation method of ectoin-hyaluronic acid composite gel and obtained product
  • Preparation method of ectoin-hyaluronic acid composite gel and obtained product
  • Preparation method of ectoin-hyaluronic acid composite gel and obtained product

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] The preparation of cross-linking agent EBD is as follows:

[0043] (1) Add 18g of 1,4-butanediol and 0.18g of boron trifluoride ethyl ether into the flask, raise the temperature to 50°C, add 9.2g of epichlorohydrin dropwise, continue to react for 4 hours after dropping, and add 100ml after cooling to room temperature Add toluene, stir, then add 10ml of sodium hydroxide (aq, 40%), and continue the reaction at 45°C for 1 hour. After the reaction, 100ml of water was added, extracted with ethyl acetate, and concentrated to obtain a yellow oily product, which was 1,4-butanediol monoglycidyl ether.

[0044] (2) Dissolve 14.6g of 1,4-butanediol monoglycidyl ether and 17.1g of ectoine in 100ml of toluene, add 0.34g of chromium 5-tert-butylfuroate, stir at 115°C for 6 hours, add 50ml of water after the reaction is completed, Ethyl acetate extraction, concentration, column chromatography, the product B was obtained.

[0045] (3) Dissolve 14.4g of product B in toluene, add 0.072...

Embodiment 2

[0047] The preparation of cross-linking agent EBD is as follows:

[0048] (1) Add 18g of 1,4-butanediol and 0.09g of boron trifluoride diethyl ether into the flask, raise the temperature to 40°C, add 7.4g of epichlorohydrin dropwise, continue the reaction for 2 hours after the drop, and add 100ml after cooling to room temperature Add toluene, stir, then add 10ml of sodium hydroxide (aq, 40%), and continue the reaction at 45°C for 1 hour. After the reaction, 100ml of water was added, extracted with ethyl acetate, and concentrated to obtain a yellow oily product, which was 1,4-butanediol monoglycidyl ether.

[0049] (2) Dissolve 14.6g of 1,4-butanediol monoglycidyl ether and 14.2g of ectoine in 100ml of acetone, add 0.071g of chromium 5-tert-butylfuroate, stir at 60°C for 2 hours, add 50ml of water after the reaction is complete, Ethyl acetate extraction, concentration, column chromatography, the product B was obtained.

[0050] (3) Dissolve 14.4g of product B in acetone, add ...

Embodiment 3

[0052] The preparation of cross-linking agent EBD is as follows:

[0053] (1) Add 18g of 1,4-butanediol and 2.7g of boron trifluoride ethyl ether into the flask, raise the temperature to 80°C, add 10.8g of epichlorohydrin dropwise, continue to react for 12 hours after dropping, cool to room temperature and add 100ml of toluene was stirred, and then 10ml of sodium hydroxide (aq, 40%) was added, and the reaction was continued at 45°C for 1 hour. After the reaction, 100ml of water was added, extracted with ethyl acetate, and concentrated to obtain a yellow oily product, which was 1,4-butanediol monoglycidyl ether.

[0054] (2) Dissolve 14.6g of 1,4-butanediol monoglycidyl ether and 28.4g of ectoine in 100ml of n-hexane, add 1.46g of chromium 5-tert-butylfuroate, stir at 80°C for 12h, add 50ml of water after the reaction , extracted with ethyl acetate, concentrated, and column chromatographed to obtain the product B.

[0055] (3) Dissolve 14.4g of product B in n-hexane, add 1.44...

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Abstract

The invention discloses a preparation method of ectoin-hyaluronic acid composite gel and an obtained product. The preparation method comprises the following steps: firstly, preparing a cross-linking agent EBD by a step-by-step method; then, subjecting the EBD and BDDE, used as mixed cross-linking agents, to a cross-linking reaction with hyaluronic acid or salt thereof to prepare cross-linked hyaluronic acid gel, adding free epsilon-polyine to the cross-linked hyaluronic acid gel again, and mixing the components to prepare the ectoin-hyaluronic acid composite gel. The composite gel provided bythe invention contains free and cross-linked ectoin, not only has a filling effect, but also can achieve anti-aging and skin repair and regeneration effects in the whole hyaluronic acid gel filling period through the matching of the two forms of ectoin; in addition, the product, as a viscoelastic agent for adjuvant therapy in glaucoma surgery, lacrimal passage occlusion surgery, vitrectomy and other surgeries, has higher potential and effect.

Description

technical field [0001] The present invention relates to a preparation method of ectoine-hyaluronic acid composite gel, and also relates to the composite gel prepared according to the method and the application of the composite gel in injection products, belonging to biomedical material technology field. Background technique [0002] Ecdoine (2-methyl-1,4,5,6,-tetrahydropyrimidine-4-carboxylic acid) is derived from high halophilic bacteria (Halomonas Elongata), and can be used in extreme conditions of high salt, high temperature, and high ultraviolet radiation Next, ectoine can protect halophilic bacteria from harm. Studies have shown that ectoine can promote cell proliferation and differentiation, and at the same time curb the expression of aging genes, fundamentally change the composition of skin cells, delay skin aging; effectively improve the immune protection ability of skin cells, increase cell repair ability, and effectively resist Invasion of microorganisms and alle...

Claims

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Application Information

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IPC IPC(8): C08L5/08C08K5/3462C08K5/1515C08J3/24C08J3/075C08B37/08C07D405/12A61L27/20A61L27/52A61L27/54A61L27/50A61L31/04A61L31/14
CPCC08J3/075C08J3/24C08K5/3462C08B37/0072C07D405/12A61L27/20A61L27/52A61L27/54A61L27/50A61L31/042A61L31/145A61L31/14C08J2305/08C08K5/1515A61L2300/216A61L2300/412A61L2400/06A61L2430/34C08L5/08
Inventor 李敏李超庞萌萌王静刘建建郭学平
Owner BLOOMAGE BIOTECHNOLOGY CORP LTD
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