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Preparation method and application of in-situ injection molded thiolated polysaccharide-based hydrogel and drug carrier thereof

An in situ injection and sulfhydrylation technology, used in drug delivery, pharmaceutical formulations, prostheses, etc., can solve the problems of poor recovery of injectable hydrogels, uncomfortable surgical operations, poor mechanical strength, etc., to promote epithelial cell growth, Promoting wound healing, low cost effect

Active Publication Date: 2019-03-08
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Currently, the most commonly used methods for preparing injectable hydrogels are UV light-induced crosslinking or the introduction of chemical crosslinking agents, but ultraviolet light crosslinking (photoinitiators) or the introduction of chemical crosslinking agents will have certain effects on cells. Potential toxic effects, while physically cross-linked injectable hydrogels have poor recovery and poor mechanical strength, making them unsuitable for surgical operations
Patent application numbers 200710058737.9 and 200710058738.3 both disclose thiolated chitosan hydrogel and its preparation method, but do not add any cross-linking agent and catalyst, and only use the oxidation of air to cross-link the disulfide bonds formed by the reaction between sulfhydryl groups Hydrogel, long time required

Method used

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  • Preparation method and application of in-situ injection molded thiolated polysaccharide-based hydrogel and drug carrier thereof
  • Preparation method and application of in-situ injection molded thiolated polysaccharide-based hydrogel and drug carrier thereof
  • Preparation method and application of in-situ injection molded thiolated polysaccharide-based hydrogel and drug carrier thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] (1) Weigh 1g of chitosan and dissolve it in 100mL of 0.5% (v / v) acetic acid aqueous solution, add 0.9586g of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiethylene Amine hydrochloride (EDAC) and 0.5754g of N-hydroxysuccinimide (NHS), stirred at room temperature for 15 minutes in the dark;

[0054] (2) Add cysteine ​​(the molar ratio of chitosan:cysteine ​​is 3:1) to the reaction system of step (1), add 1mol / L NaOH solution to adjust the system PH=5, room temperature, dark Stir the reaction for 5 hours; sequentially use HCl solution with pH=5.0, HCl solution with pH=5.0 containing 1% (w / v) NaCl and HCl solution with pH=5.0 as the dialysate, each in the dark for 1 day, and dialyze for 3 days in total. day, and finally freeze-dried to obtain the thiolated chitosan (CSSH) sample, which was preserved at 4°C;

[0055] (3) Add the thiolated chitosan prepared in step (2) into deionized water with pH = 8, fully dissolve it under magnetic stirring, put it into a refrigerator at -20°C...

Embodiment 2

[0058] (1) Weigh 1g of chitosan and dissolve it in 100mL of 0.5% (v / v) acetic acid aqueous solution, add 0.9586g of 1-ethyl-3-(3-dimethylaminopropyl)-dicarbonate Imine hydrochloride (EDAC) and 0.5754g of N-hydroxysuccinimide (NHS), stirred at room temperature for 15 minutes in the dark;

[0059] (2) Add cysteine ​​(the molar ratio of chitosan: cysteine ​​is 1:1) to the reaction system of step (1), add 1mol / L NaOH solution to adjust the system PH=5, room temperature, dark Stir the reaction for 5 hours; sequentially use HCl solution with pH=5.0, HCl solution with pH=5.0 containing 1% (w / v) NaCl and HCl solution with pH=5.0 as the dialysate, each in the dark for 1 day, and dialyze for 3 days in total. day, and finally freeze-dried to obtain the thiolated chitosan (CSSH) sample, which was preserved at 4°C;

[0060] (3) Add the thiolated chitosan prepared in step (2) into deionized water with pH = 8, fully dissolve it under magnetic stirring, put it into a refrigerator at -20°C fo...

Embodiment 3

[0063] (1) Weigh 1g of chitosan and dissolve it in 100mL of 0.5% (v / v) acetic acid aqueous solution, add 0.9586g of 1-ethyl-3-(3-dimethylaminopropyl)-dicarbonate Imine hydrochloride (EDAC) and 0.5754g of N-hydroxysuccinimide (NHS), stirred at room temperature for 15 minutes in the dark;

[0064] (2) Add cysteine ​​(the molar ratio of chitosan: cysteine ​​is 1:3) to the reaction system of step (1), add 1mol / L NaOH solution to adjust the pH of the system to 5, room temperature, dark Stir the reaction for 5 hours; sequentially use HCl solution with pH=5.0, HCl solution with pH=5.0 containing 1% (w / v) NaCl and HCl solution with pH=5.0 as the dialysate, each in the dark for 1 day, and dialyze for 3 days in total. day, and finally freeze-dried to obtain the thiolated chitosan (CSSH) sample, which was preserved at 4°C;

[0065] (3) Add the thiolated chitosan prepared in step (2) into deionized water with pH = 8, fully dissolve it under magnetic stirring, put it into a refrigerator a...

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Abstract

The invention belongs to the field of tissue engineering scaffolds, and discloses a preparation method and application of an in-situ injection molded thiolated polysaccharide-based hydrogel and a drugcarrier thereof. The in-situ injection molded thiolated polysaccharide-based hydrogel is prepared from 3-6%(w / v) of thiolated polysaccharide and 10-29% (w / v) of sodium beta-glycerophosphate, whereinthe thiolated polysaccharide can coat one or more of drug-carrying liposomes, drug-carrying thiolated halloysite or polypeptides to form the in-situ injection molded thiolated polysaccharide-based hydrogel drug carrier. The in-situ injection-molded thiolated polysaccharide-based hydrogel and the drug carrier thereof can be gelled at human physiological temperature, and have temperature sensitivity, injectability and water absorption.

Description

technical field [0001] The invention belongs to the field of tissue engineering, and in particular relates to a preparation method and application of a thiolated polysaccharide-based hydrogel capable of in-situ injection molding and a drug carrier thereof. Background technique [0002] The skin is an important part of the human body. It is in direct contact with the outside world and is vulnerable to various traumas, such as burns, scratches, infections, tumor resections, and skin ulcers caused by diabetes. The resection and recurrence of bone tumors will increase the pain of the patient in the second operation. Anti-tumor drugs can be entrapped in the gel, which can fill the defect and prevent tumor recurrence. The release of the drug can be controlled by the entrapment of the drug, and the side effects of the tumor drug can be reduced. It has a certain application prospect. [0003] Natural polysaccharide materials such as sodium alginate, hyaluronic acid, chitosan and ot...

Claims

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Application Information

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IPC IPC(8): A61L27/20A61L27/52A61L27/54
CPCA61L27/20A61L27/52A61L27/54A61L2300/216A61L2300/412A61L2300/416A61L2400/06C08L5/04C08L5/08
Inventor 李立华李日旺林振
Owner JINAN UNIVERSITY
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