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Hydrogels and Protein Drugs

A hydrogel and block copolymer technology, applied in the field of biomedical materials, can solve the problems of difficult removal of highly toxic crosslinking agents, pathogenicity, carcinogenicity, etc., and achieve the effect of maintaining biological activity and functional stability.

Active Publication Date: 2019-04-16
深圳普洛美康材料有限公司
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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

preparation example Construction

[0040] The invention provides a kind of preparation method of hydrogel, comprises the steps:

[0041] Step 1. Put the polyethylene glycol with hydroxyl groups at both ends at 120-160°C and add the degradable polymer and catalyst I under the condition of nitrogen protection. After reacting for 6-8 hours, collect the insoluble matter and put it under the condition of 20-35°C Dry to constant weight to obtain solid A; or dissolve polyethylene glycol in DCM or THF at room temperature, add catalyst II and degradable polymer, react for 5-60 minutes, ether precipitate and collect the product, dialysis and purification, and freeze-dry to obtain solid B, the degradable polymer is selected from one or more of polyglycolide, polylactide, polyglycolide lactide, polycaprolactone, and the combination of polyethylene glycol and degradable polymer The molecular weight ratio is 1: 0.1-1, the catalyst I is stannous octoate, and the catalyst II is DBU;

[0042] Step 2. Dissolve solid A or solid ...

Embodiment 1

[0069] Embodiment 1: the synthesis of crosslinking agent 1

[0070] 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 60 mL of thioethanol, then add an equimolar amount of AlCl3 to react for 24 hours; extract with DCM, and dry to obtain the 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

[0071] Embodiment 2: the synthesis of crosslinking agent 2

[0072]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 60 mL of thioethanol, then add an equimolar amount of AlCl3 to react for 24 hours; extract with DCM, and dry to obtain the 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.

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PUM

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Abstract

The invention provides a hydrogel and a protein drugs. The hydrogel comprises the following raw materials in parts by weight: 1 to 50 parts of chitosan, 0.1 to 20 parts of a crosslinking agent and 10to 100 parts of water; the crosslinking agent is prepared by combining a non-degradable raw material A and a degradable raw material B to form a block copolymer, and connecting a raw material C at thetail end of the block copolymer. The hydrogel is injectable, coatable and degradable in vivo, can well maintain the biological activity of the drug protein, and has no toxic or side effect on the hydrogel and degradation products thereof. The protein drug adopts the hydrogel to carry and disperse the drug protein, so that the biological activity and the functional stability of the drug protein can be well maintained.

Description

technical field [0001] The invention relates to the technical field of biomedical materials, in particular to a hydrogel and protein medicine. 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 protein drug...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/075C08J3/24C08L5/08C08L89/00C08G81/00A61K47/36A61K38/38A61K9/06
CPCA61K38/385A61K47/34A61K47/36A61K9/06C08G63/08C08G81/00C08J3/075C08J3/24C08J3/246C08L5/08C08J2305/08C08L2201/06C08J2489/00C08L89/00
Inventor 唐键
Owner 深圳普洛美康材料有限公司
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