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CN-121736135-B - Amination modification method of sodium alginate and application thereof

CN121736135BCN 121736135 BCN121736135 BCN 121736135BCN-121736135-B

Abstract

The invention relates to an amination modification method of sodium alginate and application thereof, and relates to the technical field of polysaccharide modification, wherein the amination modification method of sodium alginate comprises the following steps of S1, adding sodium alginate into a reaction bottle filled with buffer solution, fully stirring until a solution system is clear and transparent, S2, adding an amide activating agent into the solution system obtained in S1 for reaction, S3, adding ethylenediamine derivative with a protecting group into a reaction product obtained in S2, reacting for a second preset time at a second preset temperature, S4, adding ethanol into the reaction product obtained in S3, drying the generated primary precipitation product to obtain an intermediate, S5, adding the intermediate obtained in S4 into an acid solution or an alkali solution, stirring and reacting for a third preset time at a third preset temperature to remove the protecting group, S6, adding ethanol into the reaction product obtained in S5, carrying out secondary precipitation reaction, and drying the secondary precipitation product to obtain the amination sodium alginate.

Inventors

  • SUN FEIFEI
  • CHEN ZHIQI
  • ZHOU XIAO

Assignees

  • 江苏德威兰医疗器械股份有限公司

Dates

Publication Date
20260508
Application Date
20260226

Claims (6)

  1. 1. The amination modification method of the sodium alginate is characterized by comprising the following steps of: S1, mixing sodium alginate with a buffer solution, and fully stirring until a solution system is clear and transparent; S2, adding an amide activator into the solution system obtained in the step S1, and reacting for a first preset time at a first preset temperature; S3, adding ethylenediamine derivatives with protecting groups into the reaction product obtained in the step S2, and reacting for a second preset time at a second preset temperature; s4, adding ethanol into the reaction product obtained in the step S3, and performing primary precipitation reaction, wherein the primary precipitation product is an intermediate; S5, adding the intermediate obtained in the S4 into an acid solution or an alkali solution, and stirring at a third preset temperature for reacting for a third preset time to remove the protecting group; S6, adding ethanol into the reaction product obtained in the step S5, performing secondary precipitation reaction, filtering, dialyzing and freeze-drying the secondary precipitation product to obtain the amino sodium alginate; In the S1, the molecular weight of the sodium alginate ranges from 20K to 150K, and the buffer solution is any one of 2-morpholinoethanesulfonic acid buffer solution and phosphate buffer solution; In S2, the amide activator is any one or two of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride, N-hydroxysuccinimide, dicyclohexylcarbodiimide, 4-dimethylaminopyridine, hydroxybenzotriazole and 4- (4, 6-dimethoxytriazin-2-yl) -4-methylmorpholine hydrochloride; The molar ratio of the amide activator to the sodium alginate is (1-3): 1; In S3, the ethylenediamine derivative with the protecting group comprises the following compounds: ; Wherein R is a protecting group; the protecting group comprises any one of the following compounds: 、 ; Wherein X is a connecting main chain end; In S5, the acid solution comprises any one of trifluoroacetic acid, hydrochloric acid and p-toluenesulfonic acid, the pH value of the acid solution is 2-5, the alkali solution comprises piperidine or ammonia water, and the pH value of the alkali solution is 8-11.
  2. 2. The amination modification method of sodium alginate according to claim 1, wherein in S2, the first preset temperature is 25-60 ℃, and the first preset time is 2-8 hours.
  3. 3. The amination modification method of sodium alginate according to claim 1, wherein in S3, the molar ratio of the addition amount of ethylenediamine derivative with a protecting group to the addition amount of amide activator and sodium alginate is (1-3): 1, the second preset temperature is 0-40 ℃, and the second preset time is 6 h-18 h.
  4. 4. The amination modification method of sodium alginate according to claim 1, wherein in S4, the addition amount of ethanol is 2-3 times of the volume of a reaction product obtained in S3.
  5. 5. The amination modification method of sodium alginate according to claim 1, wherein in the step S6, after the secondary precipitation reaction, the secondary precipitation product is subjected to suction filtration, dissolution and dialysis, and then freeze drying is carried out, so that the aminated sodium alginate is obtained, the dialysis temperature is room temperature, and the dialysis bag used for dialysis has a molecular weight cut-off of 460-10000D.
  6. 6. Use of an aminated sodium alginate prepared by the amination modification method of sodium alginate as defined in any one of claims 1 to 5 in medical hydrogels.

Description

Amination modification method of sodium alginate and application thereof Technical Field The invention relates to the technical field of polysaccharide modification, in particular to an amination modification method of sodium alginate and application thereof. Background Sodium alginate is a natural anionic polysaccharide extracted from brown algae, has good hydrophilicity and biocompatibility, is stable in property in a human body, can be degraded into polysaccharide which is nontoxic and does not participate in metabolism of the organism, and is one of natural biological materials for synthesizing hydrogel. In addition, a large number of-OH and-COOH polar groups exist on the skeleton of the alginate, and the skeleton is modified by a chemical method, so that the skeleton can be used for preparing composite hydrogel by chemical crosslinking with other natural polymer materials or synthetic polymer materials. The amino sodium alginate has the core advantages that the amino sodium alginate has the diversity of reaction sites, and simultaneously has the inherent carboxyl (-COOH) of sodium alginate and the newly introduced (-NH 2), so that the newly introduced amino can be efficiently reacted with aldehyde groups (Schiff base reaction), NHS esters, epoxides and the like on the basis of keeping the original advantages of sodium alginate, the covalent crosslinking with mild and good biocompatibility is realized, a more stable hydrogel network is formed, and the problems of poor mechanical property, poor stability and the like of the traditional ionic crosslinking (such as calcium ion crosslinking) are solved. However, the amination modification of sodium alginate still has a plurality of defects at present, and the patent of the invention with the authority of publication number CN106478995B discloses a sodium alginate-based hydrogel and a preparation method thereof, wherein the sodium alginate-based hydrogel is prepared from the following raw materials, by weight, 100-300 mg of amination sodium alginate, 20-100 mg of L-lysine or 25-120 mg of L-arginine or 18-90 mg of L-ornithine, 20-100 mg of nano ferroferric oxide magnetic particles and 50-300 mg of sodium alginate oxide. The preparation method of the amino sodium alginate comprises the steps of adjusting the pH value of a sodium alginate aqueous solution with the concentration of 5-30 g/L to 4.0-6.5, stirring at 60-90 ℃ for 0.5-6 hours, cooling to 15-45 ℃, adding a mixture of carbodiimide hydrochloride and N-hydroxysuccinimide or a mixture of carbodiimide hydrochloride and 1-hydroxybenzotriazole, adding a diamine compound, reacting for 1-18 hours, dialyzing, and freeze-drying to obtain the amino sodium alginate. Diamine (such as ethylenediamine, hexamethylenediamine and oxalic dihydrazide) contains two primary amino groups with equal activity, on one hand, the grafting reaction has poor selectivity and uncontrollable structure, single-point grafting can possibly occur, double-point crosslinking can possibly occur, so that the grafting sites of sodium alginate molecules are nonuniform, the molecular structure is highly random, the grafting degree and the molecular configuration are difficult to precisely control, on the other hand, one end of the double primary amino group of the diamine reacts with a sodium alginate A chain, the other end of the double primary amino group reacts with a B chain, intermolecular crosslinking is caused, the solution viscosity is increased, even gelation is caused, and the subsequent hydrogel synthesis cannot be completed. In conclusion, the reaction process of the sodium alginate grafted diamine is difficult to control, the process stability is poor, and the yield is low. Disclosure of Invention The invention provides an amination modification method of sodium alginate and application thereof, aiming at solving one or more of the technical problems in the prior art. The invention provides an amination modification method of sodium alginate, which solves the technical problems and comprises the following steps: S1, mixing sodium alginate with a buffer solution, and fully stirring until a solution system is clear and transparent; S2, adding an amide activator into the solution system obtained in the step S1, and reacting for a first preset time at a first preset temperature; S3, adding ethylenediamine derivatives with protecting groups into the reaction product obtained in the step S2, and reacting for a second preset time at a second preset temperature; s4, adding ethanol into the reaction product obtained in the step S3, and performing primary precipitation reaction, wherein the primary precipitation product is an intermediate; S5, adding the intermediate obtained in the S4 into an acid solution or an alkali solution, and stirring at a third preset temperature for reacting for a third preset time to remove the protecting group; And S6, adding ethanol into the reaction product obtained in the step S5, performing secondary precipita