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Hydrogel and preparation method thereof

A hydrogel and raw material technology, applied in the field of biomedical materials, can solve the problems of highly toxic cross-linking agents that are difficult to remove, cause disease, and cause cancer, etc., and achieve relaxed storage time and storage conditions, cost reduction, and mild gelation conditions Effect

Inactive Publication Date: 2016-10-26
深圳诺坦药物技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Its disadvantages include that the non-crosslinked sol will be quickly eliminated in the body; the block of the thermosensitive physical hydrogel contains a large number of synthetic polymers, and the degradation products also have the potential risk of acid accumulation; the highly toxic crosslinking agent is not easy to completely Cleared, there are potential safety hazards of carcinogenicity and disease-causing

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Embodiment 1: the synthesis of crosslinking agent 1

[0055] 0.5g mPEG (5000) was dissolved in 1mL DCM, and 10mg DBU was added; 0.8g lactide (LA) was dissolved in 5mL DCM; the LA solution was transferred into the mPEG solution and stirred for 10min; the product I was obtained by precipitation with ether. Dissolve the product I in 60mL of thioethanol, then add an equimolar amount of AlCl 3 Reacted for 24 hours; extracted with DCM and dried to give product II. Dissolve product II in 100 mL DCM, then add 5-fold molar amount of aldehyde benzoic acid and EDC, 0.5-fold molar amount of DMAP, and react for 24 hours; Precipitate product III with ether, which is crosslinker 1. The number-average and weight-average molecular weights (Mn, Mw) of the crosslinking agent 1 measured by GPC were 10619 and 10848, respectively, and the polydispersity index (Mw / Mn) was 1.02.

Embodiment 2

[0056] Embodiment 2: the synthesis of crosslinking agent 2

[0057] 0.5g mPEG (5000) was dissolved in 1mL DCM, and 10mg DBU was added; 0.75g lactide (LA) and 0.3g glycolide (GA) were dissolved in 5mL DCM; the LA / GA solution was transferred into the mPEG solution and stirred for 10min; The product I was obtained by ether precipitation. Dissolve the product I in 60mL of thioethanol, then add an equimolar amount of AlCl 3 Reacted for 24 hours; extracted with DCM and dried to give product II. Dissolve product II in 100 mL DCM, then add 5-fold molar amount of aldehyde benzoic acid and EDC, 0.5-fold molar amount of DMAP, and react for 24 hours; Precipitate product III with ether, which is cross-linking agent 2. The number-average and weight-average molecular weights (Mn, Mw) of the crosslinking agent 2 measured by GPC were 9820 and 10017, respectively, and the polydispersity index (Mw / Mn) was 1.03.

Embodiment 3

[0058] Embodiment 3: the synthesis of crosslinking agent 3

[0059] 0.5g PEG (5000) was dissolved in 1mL DCM, and 10mg DBU was added; 0.05g LA was dissolved in 5mL DCM; LA solution was transferred into mPEG solution, stirred for 10min; product I was obtained by ether precipitation. Dissolve the product I in 60mL of thioethanol, then add an equimolar amount of AlCl 3 Reacted for 24 hours; extracted with DCM and dried to give product II. Dissolve product II in 100 mL DCM, then add 5-fold molar amount of aldehyde benzoic acid and EDC, 0.5-fold molar amount of DMAP, and react for 24 hours; Precipitate product III with ether, which is crosslinker 3. The number-average and weight-average molecular weights (Mn, Mw) of the crosslinking agent 3 measured by GPC were 5403 and 5587, respectively, and the polydispersity index (Mw / Mn) was 1.03.

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Abstract

The invention provides hydrogel which comprises the following raw materials in parts by weight: 1-50 parts of chitosan, 0.1-20 parts of a cross-linking agent and 10-100 parts of water, wherein the cross-linking agent comprises the following raw materials in parts by weight: 1-5 parts of a raw material A and 0.1-5 parts of a raw material B; after the raw material A is combined with the raw material B, a raw material C is connected with the final end of the mixture; the raw material A is polyethylene glycol; the raw material B is a degradable polymer; the raw material B is selected from one or more of polyglycollide, polylactide, polyglycollide lactide and polycaprolactone; and the raw material C is selected from one or more of glyoxylic acid, uronic acid and aldehyde benzoic acid. The invention further provides a preparation method of the hydrogel. The hydrogel has the beneficial effects that a reaction product of polyethylene glycol and the degradable polymer is enabled to react with glyoxylic acid, uronic acid and aldehyde benzoic acid, and the obtained cross-linking agent and chitosan form the hydrogel automatically in a solution.

Description

technical field [0001] The invention relates to the technical field of biomedical materials, in particular to a hydrogel and a preparation method thereof. Background technique [0002] People have recognized the therapeutic effect of protein for a long time. For example, antiserum was prepared to treat diphtheria in the 19th century; insulin was isolated from cow and pig pancreas to treat diabetes in the early 20th century. However, there are limitations in the application of these human-derived or animal-derived proteins, such as limited production, cross-virus infection, and immune response of patients. Therefore, before the birth of gene recombination technology, protein drugs were not able to enter clinical application on a large scale. Insulin prepared by gene recombination technology in 1982 was the first recombinant protein drug approved by the US FDA, which opened the door for therapeutic proteins to enter the clinic on a large scale. So far, more than one hundred ...

Claims

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Application Information

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IPC IPC(8): C08J3/075C08J3/24C08L5/08C08L89/00C08G63/08C08G81/00A61K9/06A61K47/36A61K47/34
CPCA61K38/385A61K47/34A61K47/36A61K9/06C08G63/08C08G81/00C08J3/075C08J3/24C08J3/246C08L5/08C08J2305/08C08L2201/06C08J2489/00C08L89/00
Inventor 唐键
Owner 深圳诺坦药物技术有限公司
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