CN-122011235-A - Azido carboxymethyl chitosan, glucose responsive polysaccharide-based hydrogel, and preparation method and application thereof

CN122011235ACN 122011235 ACN122011235 ACN 122011235ACN-122011235-A

Abstract

The invention belongs to the technical field of high polymer materials, and particularly relates to an azido carboxymethyl chitosan, glucose responsive polysaccharide-based hydrogel, a preparation method and application thereof. The azido carboxymethyl chitosan is obtained by taking carboxymethyl chitosan and fluorosulfonyl azide as raw materials to carry out an azido reaction. According to the invention, the azido carboxymethyl chitosan is prepared by directly reacting FSO 2 N 3 with carboxymethyl chitosan for the first time, the reaction condition is mild, the product purity is high, and a new technical route is provided for polysaccharide modification. The glucose-responsive polysaccharide-based hydrogel which is covalently connected with polyphenols is prepared by further utilizing the azido carboxymethyl chitosan, has the properties of glucose-responsive release, antioxidation, antibiosis and promotion of cell migration, and can effectively promote the healing of diabetic wounds.

Inventors

WEI XIAOFENG
ZHANG JIYE
WANG LEI
WANG BOBO
FAN CHUNYING
MA JIA
LI JIAN

Assignees

西安交通大学
陕西吾方医疗科技有限公司

Dates

Publication Date: 20260512
Application Date: 20260210

Claims (10)

1. A preparation method of azido carboxymethyl chitosan is characterized in that the azido carboxymethyl chitosan is obtained by taking carboxymethyl chitosan and fluorosulfonyl azide as raw materials to carry out an azido reaction.
2. The preparation method of claim 1, wherein the dosage ratio of the carboxymethyl chitosan to the fluorosulfonyl azide solution is 220.0 mg:0.01 mL-0.5 mL, the concentration of the fluorosulfonyl azide solution is 165-170 mmol/L, and the azide reaction is carried out at 20-50 ℃ for 12-24 h.
3. An azidomethyl chitosan prepared according to the method of any one of claims 1-2.
4. A method for preparing a glucose-responsive polysaccharide-based hydrogel using the carboxymethylchitosan azide of claim 3, comprising the steps of: Adding the C domain polypeptide of the alkynyl insulin-like growth factor 1, a copper source and a reducing agent into the solution of the azido carboxymethyl chitosan, and performing click reaction to obtain modified carboxymethyl chitosan; carrying out condensation reaction under the action of a coupling agent by taking aldehyde sodium alginate and 3-aminophenylboric acid as raw materials to obtain modified sodium alginate; Adding polyphenols into the modified carboxymethyl chitosan solution, mixing with the modified sodium alginate solution, and crosslinking the amino groups of the modified carboxymethyl chitosan and the carboxyl groups of the modified sodium alginate through Schiff base reaction, wherein the polyphenols are connected into a hydrogel network through boron ester bonds and hydrogen bonds, so that the glucose-responsive polysaccharide-based hydrogel is obtained.
5. The method according to claim 4, wherein the aldehyde sodium alginate is obtained by adding an oxidizing agent to an aqueous solution of sodium alginate for oxidation reaction.
6. The method of claim 5, wherein the step of determining the position of the probe is performed, The click reaction is carried out for 12-24 hours at the temperature of 30-50 ℃; the condensation reaction is carried out for 12-24 hours at the temperature of 30-50 ℃; The oxidant is sodium periodate, the oxidation reaction is carried out for 2-8 hours at 20-50 ℃, and after the reaction is finished, ethylene glycol is added to terminate the reaction for 1-3 hours.
7. The method of claim 4, wherein the copper source is a water-soluble copper salt, the reducing agent is sodium ascorbate, the coupling agent is 1-ethyl- (3-dimethylaminopropyl) carbodiimide, and the polyphenols are epigallocatechin gallate.
8. The method of claim 7, wherein the step of determining the position of the probe is performed, The mass ratio of the azido carboxymethyl chitosan to the C domain polypeptide of the alkynyl insulin-like growth factor 1 is 55:6.5-37.5; the mass ratio of the modified carboxymethyl chitosan to the epigallocatechin gallate to the modified sodium alginate is 1-10:0.1-1:1-10.
9. A glucose-responsive polysaccharide-based hydrogel prepared according to the method of claim 4.
10. Use of a glucose-responsive polysaccharide-based hydrogel according to claim 9, comprising any one of the following: (1) Preparing a product for promoting wound healing; (2) Preparing an antioxidant product; (3) And preparing an antibacterial product.

Description

Azido carboxymethyl chitosan, glucose responsive polysaccharide-based hydrogel, and preparation method and application thereof Technical Field The invention belongs to the technical field of high polymer materials, and particularly relates to an azido carboxymethyl chitosan, glucose responsive polysaccharide-based hydrogel, a preparation method and application thereof. Background Chitosan is a natural cationic polysaccharide, a deacetylated product of chitin, and its precursor mainly originates from marine arthropods, fungal cell wall structures and insect cuticle. Because of its good biocompatibility, degradability and antibacterial activity, chitosan has become an important direction in the development of biomedical materials. However, intramolecular hydrogen bonding of chitosan results in its dissolution only under acidic conditions, which severely restricts its application in the biomedical field. Thus, researchers often modify the structure of chitosan using chemical modification strategies, with carboxymethyl chitosan (CMCS) being considered one of the most potential derivatization products due to its good solubility and functional adjustability. CMCS introduces a carboxymethyl group with strong hydrophilicity while retaining the inherent bioactivity of chitosan, thereby realizing stable dissolution in a wide pH range. The CMCS azide modification is a modification method with good application prospect, the CMCS after the azide has high reactivity, can perform click chemical reaction with alkynyl under mild conditions, has high efficiency and specificity, can realize the accurate modification of the CMCS, and has good stability. The conventional preparation method of the polysaccharide azide generally adopts a two-step method of sulfonylation-azide, namely, firstly, sulfonate groups are introduced as leaving groups through sulfonylation reaction, and then nucleophilic substitution reaction is carried out with sodium azide. The method has the defects of harsh reaction conditions, more byproducts, low product purity and the like. Disclosure of Invention The invention provides a preparation method of azido carboxymethyl chitosan, which is characterized in that FSO 2N3 is directly reacted with carboxymethyl chitosan, so that the defect of a two-step method of sulfonylation-azidation in the traditional method is avoided. The invention provides the following technical scheme: in a first aspect of the present invention, there is provided a method for preparing an azido carboxymethyl chitosan, which is obtained by performing an azido reaction using carboxymethyl chitosan and fluorosulfonyl azide as raw materials. As a preferred embodiment of the invention, the dosage ratio of the carboxymethyl chitosan to the fluorosulfonyl azide solution is 220.0 mg:0.01 mL-0.5 mL, the concentration of the fluorosulfonyl azide solution is 165-170 mmol/L, and the azide reaction is carried out for 12-24 hours at 20-50 ℃. In a second aspect of the present invention, there is provided a carboxymethyl chitosan azide prepared according to the above method. In a third aspect of the present invention, there is provided a method for preparing a glucose-responsive polysaccharide-based hydrogel using the carboxymethylchitosan azide, comprising the steps of: Adding the C domain polypeptide of the alkynyl insulin-like growth factor 1, a copper source and a reducing agent into the solution of the azido carboxymethyl chitosan, and performing click reaction to obtain modified carboxymethyl chitosan; carrying out condensation reaction under the action of a coupling agent by taking aldehyde sodium alginate and 3-aminophenylboric acid as raw materials to obtain modified sodium alginate; Adding polyphenols into the modified carboxymethyl chitosan solution, mixing with the modified sodium alginate solution, and crosslinking the amino groups of the modified carboxymethyl chitosan and the carboxyl groups of the modified sodium alginate through Schiff base reaction, wherein the polyphenols are connected with each other through boron ester bonds and hydrogen bonds, so that the glucose-responsive polysaccharide-based hydrogel is obtained. As a preferred embodiment of the invention, the aldehyde sodium alginate is obtained by adding an oxidant into an aqueous solution of sodium alginate for oxidation reaction. As a preferred embodiment of the invention, the click reaction is carried out for 12-24 hours at 30-50 ℃; the condensation reaction is carried out for 12-24 hours at the temperature of 30-50 ℃; The oxidant is sodium periodate, the oxidation reaction is carried out for 2-8 hours at 20-50 ℃, and after the reaction is finished, ethylene glycol is added to terminate the reaction for 1-3 hours. As a preferred embodiment of the present invention, the copper source is a water-soluble copper salt, the reducing agent is sodium ascorbate, the coupling agent is 1-ethyl- (3-dimethylaminopropyl) carbodiimide, and the polyphenols are epigallocatechin gallate.