阅读说明：本技术 一种抗溶胀水凝胶材料及其制备方法 (Anti-swelling hydrogel material and preparation method thereof ) 是由 高扬 卢同庆 陈娇娇 韩修远 夏崟 于 2020-06-29 设计创作，主要内容包括：本发明提供了一种抗溶胀水凝胶材料及其制备方法,所述制备方法包括如下步骤：(1)将温敏性水凝胶前驱体溶液与带有功能性基团的聚合物混合,得到水凝胶混合溶液；(2)将碱溶液与水凝胶混合溶液混合、固化,得到所述抗溶胀水凝胶材料。本发明提供的水凝胶材料具有优异的抗溶胀的能力以及具有较好的力学韧性和与生物组织等具有较好的粘结性,因此,当本发明提供的水凝胶材料用于创口的粘结时,其具有的力学性能和粘结性能可以很好的贴合创口,使创口愈合；同时,其具有的可抑制溶胀的特点可以避免水凝胶材料从创口表面脱落或者脱粘。(The invention provides an anti-swelling hydrogel material and a preparation method thereof, wherein the preparation method comprises the following steps: (1) mixing the temperature-sensitive hydrogel precursor solution with a polymer with a functional group to obtain a hydrogel mixed solution; (2) and mixing and curing the alkali solution and the hydrogel mixed solution to obtain the anti-swelling hydrogel material. The hydrogel material provided by the invention has excellent anti-swelling capacity, better mechanical toughness and better cohesiveness with biological tissues and the like, so that when the hydrogel material provided by the invention is used for adhering wounds, the mechanical property and the cohesiveness of the hydrogel material can be well attached to the wounds, and the wounds are healed; meanwhile, the hydrogel material can be prevented from falling off or debonding from the wound surface due to the characteristic of the hydrogel material capable of inhibiting swelling.)

1. A preparation method of an anti-swelling hydrogel material is characterized by comprising the following steps:

(1) mixing the temperature-sensitive hydrogel precursor solution with a polymer with a functional group to obtain a hydrogel mixed solution;

(2) and mixing and curing the alkali solution and the hydrogel mixed solution to obtain the anti-swelling hydrogel material.

2. The method according to claim 1, wherein the method for preparing the temperature-sensitive hydrogel precursor solution comprises: and mixing a temperature-sensitive monomer, a cross-linking agent and an initiator in a solvent to obtain the temperature-sensitive hydrogel precursor solution.

3. The production method according to claim 2, wherein the temperature-sensitive monomer is selected from the group consisting of N-isopropylacrylamide;

preferably, the cross-linking agent is selected from methylene bisacrylamide;

preferably, the initiator is selected from alpha-ketoglutaric acid or ammonium persulfate;

preferably, the free radical polymerization is initiated by ultraviolet light or thermally.

4. The production method according to claim 2 or 3, wherein the concentration of the temperature-sensitive monomer is 1 to 2 mol/L;

preferably, the concentration of the cross-linking agent is 0.1-0.2 mmol/L.

5. The method for preparing a polymer according to any one of claims 1 to 4, wherein the polymer having a functional group comprises any one or a combination of at least two of chitosan, carboxymethyl chitosan, sodium alginate, hyaluronic acid, cellulose, or polyacrylic acid.

6. The production method according to any one of claims 1 to 5, wherein the mass ratio of the temperature-sensitive hydrogel precursor solution to the polymer having a functional group is 100 (2-4).

7. The production method according to any one of claims 1 to 6, wherein the alkali solution is preferably an aqueous sodium hydroxide solution;

preferably, the concentration of the sodium hydroxide aqueous solution is 2-3 mol/L.

8. The production method according to any one of claims 1 to 7, wherein the alkali solution is added in an amount to adjust the pH of the hydrogel mixed solution of step (2) to 5.1 to 5.5;

preferably, the curing is photo-curing or thermal curing for 8-10 h.

9. An anti-swelling hydrogel material prepared by the preparation method according to any one of claims 1 to 8.

10. The anti-swelling hydrogel material according to claim 9, wherein the anti-swelling hydrogel material comprises a double network hydrogel structure formed by interpenetrating a first network hydrogel structure and a second network hydrogel structure;

preferably, the first network hydrogel structure is selected from temperature-sensitive hydrogel structures, and the second network hydrogel structure is a natural cationic hydrogel structure;

preferably, the mass ratio of the first network hydrogel structure to the second network hydrogel structure is 100 (2-4).

Technical Field

The invention belongs to the technical field of medical supplies, and relates to an anti-swelling hydrogel material and a preparation method thereof.

Background

Wound healing of wounds of internal organs, connective tissues, muscles, skin and flesh etc. has been a focus of research in the biomedical field. Suturing is a traditional wound closing method, but the surgical suturing inevitably causes damage to tissues around the wound, the inability to suture some special wounds and the problems of time and labor consumption and the like. The hydrogel is a three-dimensional network formed by natural or synthetic polymers and a large number of water molecules, and the excellent biocompatibility of the hydrogel enables the hydrogel to be rapidly developed in the biomedical field. The strong adhesion of hydrogel materials to biological tissues has made a breakthrough in recent years, and it is expected that the hydrogel will be used as an adhesive tape instead of suturing by adhesion.

The existing hydrogel is bonded with biological tissues, and due to the lack of mechanical structure design of the hydrogel, the mechanical properties of the hydrogel and the bonding energy of the hydrogel with the biological tissues are generally low. Meanwhile, in the prior art, hydrogel is bonded with biological epidermis (with low humidity) or biological organs in vitro, and the hydrogel is not bonded in vivo. And the traditional hydrogel has high water content, and once the hydrogel is applied to a living body, swelling behaviors with different degrees can occur, so that the bonding capability and even debonding are greatly influenced.

CN107281541A discloses a preparation method of medical temperature-sensitive hydrogel, which comprises the steps of dissolving and mixing raw materials of carboxymethyl chitosan, polyvinyl alcohol, sodium alginate and silver nitrate, adding ascorbic acid water solution and glutaraldehyde, obtaining crude gel by adopting a microwave radiation method, washing the crude gel with dilute acetic acid and water, and drying in vacuum at 40 ℃ to constant weight to obtain the medical temperature-sensitive hydrogel. The hydrogel material provided in this patent application has a good bacteriostatic activity, but also has no cohesiveness to wounds and can be used in vivo. CN104804116A discloses a method for preparing a hydrogel/base cloth composite membrane, which comprises mixing monomers of hydrogel polymers, inorganic nanoparticles, an initiator, a cross-linking agent and a catalyst, and then adding the mixture into a base cloth for polymerization, wherein the monomers of the hydrogel polymers partially permeate into the base cloth by using a gap structure of the base cloth, and the monomers of the hydrogel polymers polymerize and the base cloth to form a composite membrane, thereby obtaining the hydrogel/base cloth composite membrane, which has a certain mechanical property, but does not realize the adhesion of a wound of a hydrogel material in a living body, and does not study whether the hydrogel material is debonded under body fluid.

Therefore, it is necessary to provide a hydrogel material with strong cohesiveness, which can be applied in vivo to meet the application requirements.

Disclosure of Invention

The invention aims to provide an anti-swelling hydrogel material and a preparation method thereof; the hydrogel material provided by the invention has excellent anti-swelling capacity, better mechanical toughness and better cohesiveness with biological tissues and the like, so that when the hydrogel material provided by the invention is used for adhering wounds (or wounds), the mechanical property and the cohesiveness of the hydrogel material can be well attached to the wounds, so that the wounds are healed; meanwhile, the hydrogel material can be prevented from falling off or debonding from the wound surface due to the characteristic of the hydrogel material capable of inhibiting swelling.

In order to achieve the purpose, the invention adopts the following technical scheme:

in a first aspect, the present invention provides a method for preparing an anti-swelling hydrogel material, comprising the steps of:

(1) mixing the temperature-sensitive hydrogel precursor solution with a polymer with a functional group to obtain a hydrogel mixed solution;

(2) and mixing and curing the alkali solution and the hydrogel mixed solution to obtain the anti-swelling hydrogel material.

Wherein the temperature-sensitive hydrogel is in a contracted state at a temperature of more than 32 ℃.

The hydrogel material provided by the invention is specifically selected to comprise a temperature-sensitive hydrogel material which is in a contraction state under the environment of body temperature, so that when the hydrogel material provided by the invention is used for bonding wounds or traumas in the environment of in vivo, the phenomenon that the bonding capability of the hydrogel is reduced or the hydrogel is debonded due to swelling in the environment of body fluid (or blood) is avoided, and therefore, the hydrogel material provided by the invention can be ensured to be capable of realizing the strong bonding and the non-debonding of the wounds or the traumas.

The wound of the invention can be large-area irregular wound such as burn, scald and the like, and the wound generally refers to internal organ rupture, scratch, insertion wound and the like.

Preferably, the preparation method of the temperature-sensitive hydrogel precursor solution comprises the following steps: and mixing a temperature-sensitive monomer, a cross-linking agent and an initiator in a solvent to obtain the temperature-sensitive hydrogel precursor solution.

Preferably, the temperature sensitive monomer is selected from N-isopropylacrylamide.

Preferably, the cross-linking agent is selected from methylene bis acrylamide.

Preferably, the initiator is selected from alpha-ketoglutaric acid or ammonium persulfate.

Preferably, the free radical polymerization is initiated by ultraviolet light or thermally.

Preferably, the concentration of the temperature-sensitive monomer is 1 to 2mol/L, such as 1.2mol/L, 1.4mol/L, 1.5mol/L, 1.6mol/L, 1.8mol/L, and the like.

Preferably, the concentration of the cross-linking agent is 0.1-0.2mmol/L, such as 0.12mmol/L, 0.14mmol/L, 0.15mmol/L, 0.16mmol/L, 0.18mmol/L and the like.

Preferably, the polymer with functional groups comprises any one of chitosan, carboxymethyl chitosan, sodium alginate, hyaluronic acid, cellulose or polyacrylic acid or a combination of at least two of the above.

Preferably, the mass ratio of the temperature-sensitive hydrogel precursor solution to the natural cationic monomer is 100 (2-4), such as 100:2.5, 100:3, 100:3.5, and the like.

The addition amount of the temperature-sensitive hydrogel precursor and the polymer with the functional group is required to be within the limited range of the invention, so that the finally obtained hydrogel material has good mechanical property, good bonding property and good swelling resistance; if the addition amount of the temperature-sensitive hydrogel precursor is large, the adhesive property with tissues near the wound and the like is reduced, and the mechanical property is reduced; if the amount of the polymer having a functional group added is large, the swelling resistance is poor, and the resulting hydrogel material may partially swell to cause a slight decrease in adhesive properties.

Preferably, the alkali solution is preferably an aqueous sodium hydroxide solution.

Preferably, the concentration of the aqueous sodium hydroxide solution is 2-3mol/L, such as 2.2mol/L, 2.4mol/L, 2.5mol/L, 2.6mol/L, 2.8mol/L, and the like.

Preferably, the alkali solution is added in an amount to adjust the pH of the hydrogel mixed solution of step (2) to 5.1 to 5.5, for example, 5.2, 5.3, 5.4, etc.

Preferably, the curing is photo-curing or thermal curing for a time of 8-10h, such as 8.5h, 9h, 9.5h, etc.

In a second aspect, the present invention provides an anti-swelling hydrogel material prepared according to the preparation method of the first aspect.

Preferably, the anti-swelling hydrogel material comprises a double-network hydrogel structure formed by interpenetrating a first network hydrogel structure and a second network hydrogel structure.

Preferably, the first network hydrogel structure is selected from temperature sensitive hydrogel structures and the second network hydrogel structure is a natural cationic hydrogel structure.

Preferably, the mass ratio of the first network hydrogel structure to the second network hydrogel structure is 100 (2-4), such as 100:2.5, 100:3, 100:3.5, etc.

The hydrogel material provided by the invention adopts a double-layer interpenetrating network structure, and introduces a hydrogel network which can form strong cohesiveness with tissues near the wound on the basis of a chemically crosslinked hydrogel network with temperature-sensitive characteristic; therefore, the hydrogel material provided by the invention can realize strong adhesion with tissues, has good mechanical property, avoids hydrogel fracture caused by wound tension, has the characteristic of swelling resistance, and can avoid the phenomenon of debonding caused by swelling in the environment of body fluid (or blood).

Compared with the prior art, the invention has the following beneficial effects:

(1) the hydrogel material provided by the invention shrinks under the body temperature environment, so that the viscosity reduction or debonding behavior caused by the swelling of the hydrogel material in the body fluid or blood environment can be avoided;

(2) the hydrogel material provided by the invention can generate covalent bond reaction with tissues near the wound, so that the hydrogel material has excellent bonding performance;

(3) the hydrogel material provided by the invention has excellent mechanical properties, and can avoid phenomena such as fracture of the hydrogel material caused by wound tension;

(4) the preparation method of the hydrogel material provided by the invention is carried out in a water system, does not use any toxic or organic reagent, is green and environment-friendly, has low cost, and is suitable for large-scale preparation and application;

(5) the hydrogel material provided by the invention can be suitable for injury parts in a large range, has good biocompatibility and can avoid secondary infection.

Detailed Description

The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.