A method for preparing a semi-interpenetrating network antibacterial gel based on natural polymers

Abstract

The invention discloses a method for preparing a semi-interpenetrating network antibacterial gel based on natural polymers by a click reaction of amino groups and anhydrides in water, comprising the following steps: first, modifying natural polymers such as natural products cellulose and chitosan with quaternary ammonium salts to obtain polymers with antibacterial properties; loading metallic silver with halloysite to prepare nanoparticles with antibacterial properties, then dissolving quaternary ammonium salted natural macromolecules, nanoparticles, and copolymers containing anhydrides and amino groups in water to form a uniform solution, utilizing the click reaction between amino groups and anhydrides in water to obtain a hydrogel, soaking with water to remove uncrosslinked components, and freeze-drying to obtain an aerogel with antibacterial properties. The gel of the invention is rapidly generated in water, has a simple preparation process, and the obtained gel has pH responsiveness, and can be used in many fields such as drug sustained release, tissue engineering, and water treatment.

Description

Technical Field

[0001] The invention belongs to the field of polymer materials and relates to a method for preparing a semi-interpenetrating network antibacterial gel based on natural polymers by utilizing a click reaction between amino groups and acid anhydrides in water. Background Art

[0002] Due to the special properties of hydrogels, hydrogels have great application potential in water treatment, drug sustained release, agriculture and other fields. Among them, smart hydrogels that can respond to environmental stimuli (temperature, pH, electric field, magnetic field, etc.) are particularly eye-catching. Since pH is a common environmental change in organisms and in nature, it is of great significance to study pH-sensitive smart hydrogels. According to the different structures of hydrogels, hydrogels can be divided into single network hydrogels, semi-interpenetrating network hydrogels and fully interpenetrating network hydrogels. Among them, semi-interpenetrating network hydrogels are composed of one or more linear macromolecules and a cross-linked polymer network. The linear macromolecule chains are interspersed in the network of cross-linked polymers, and there is no covalent connection between the cross-linked polymers and the interspersed linear macromolecules. Semi-interpenetrating network hydrogels retain the characteristics of each polymer in the semi-interpenetrating network hydrogel, and also enhance the overall mechanical strength of the hydrogel and the speed of response to environmental stimuli.

[0003] According to their formation principle, hydrogels can be divided into physically cross-linked hydrogels and chemically cross-linked hydrogels. Physically cross-linked hydrogels are gels formed by forces such as van der Waals forces, hydrogen bonds, crystallization, and ion complexation. The gel generally has reversible thixotropy, but its mechanical strength is low. Chemically cross-linked hydrogels have higher mechanical strength. The reaction commonly used to prepare chemically cross-linked hydrogels is free radical polymerization, but initiators are often required, which limits the application of hydrogels. For this reason, people continue to develop new methods for preparing hydrogels. Among these methods, the preparation method of hydrogels based on click reactions has attracted much attention. Click reaction is a general term for a class of reactions with the characteristics of modular reaction, high efficiency, rapidity, and mild conditions. At present, the types of click reactions are constantly expanding, such as reactions between amino-aldehyde groups, amino-alkenyl groups, and amino-epoxy groups are also classified as click reactions. Although the traditional azide-alkyne Husigen cycloaddition click reaction has the advantages of strong selectivity, mild conditions, and high yield, the residual copper catalyst in the product, which is difficult to remove, will affect the biocompatibility of the hydrogel. Although the use of alkynyl compounds containing high-tension rings can avoid the use of copper catalysts, the preparation process is complicated, which limits its application and promotion. Therefore, it is of great significance to develop a click reaction that does not require catalysts, organic solvents, and is simple to operate to prepare hydrogels.

[0004] On the other hand, how to give the gel antibacterial properties is a problem that needs to be considered during the use of the gel. Antibacterial materials can be divided into natural, inorganic, and organic [Yang Ming et al., Guangzhou Chemical Industry, 2010, 38 (12): 18-20]. Natural antibacterial materials include chitosan, biopeptides, etc., inorganic materials mainly include silver antibacterial materials, zinc antibacterial materials, copper antibacterial materials, etc., and organic materials include quaternary ammonium salts, biguanides, etc. Chitosan has a broad spectrum of antibacterial properties and has good antibacterial properties against molds and bacteria. Among metal ion antibacterial agents, silver ion antibacterial agents are the best antibacterial agents that are harmless to the human body. Quaternary ammonium salt antibacterial agents rely on ammonium cations to tightly adhere to the surface of the bacterial cell wall, resulting in the destruction of the cell membrane and cell wall, thereby inhibiting bacterial growth. In recent years, people have paid great attention to the research of composite antibacterial materials to fully improve the antibacterial properties of the materials. Summary of the invention

[0005] The purpose of the present invention is to prepare a semi-interpenetrating network antibacterial gel based on natural macromolecules through a click reaction between anhydride and amino groups in water without a catalyst, so as to overcome the problems existing in the preparation and application of traditional gels. The method prepares a semi-interpenetrating network antibacterial hydrogel through a click reaction between anhydride and amino groups, and the reaction conditions are mild, the reaction time is short, and it is simple and easy to operate. By quaternizing natural macromolecules and adding inorganic nanoparticles with antibacterial properties in the process of preparing the gel, a semi-interpenetrating network gel with antibacterial properties is prepared by a "one-pot method".

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] (1) Preparation of water-soluble polymers containing acid anhydrides.

[0008] (2) Use quaternary ammonium compounds to modify natural products such as cellulose and chitosan.

[0009] (3) Dissolve polymers containing amino groups and acid anhydrides, natural products modified with quaternary ammonium salts, and inorganic nanoparticles in water.

[0010] (4) Add a small amount of alkali to adjust the pH of the solution to >7, and heat it to form a hydrogel through a click reaction between the amino group and the acid anhydride.

[0011] (5) The prepared semi-IPN hydrogel is placed in distilled water to remove impurities remaining in the hydrophilic network hydrogel, and then freeze-dried to obtain aerogel.

[0012] In the step (1), a water-soluble polymer containing amino groups and anhydrides is synthesized by a set method. The polymer containing amino groups can be a hyperbranched polymer or a linear polymer, and can contain both free amino groups and amino hydrochlorides. The polymer containing anhydrides can be prepared by polymerizing maleic anhydride or itaconic anhydride with different hydrophilic monomers, and can be a binary copolymer or a multi-component copolymer. The hydrophilic monomer used can be one or more of acrylamide, N-isopropylacrylamide, (meth)acrylic acid, 2-acrylamido-2-methylpropanesulfonic acid and the like.

[0013] The natural product modified with the quaternary ammonium salt in step (2) may be fiber, chitosan, etc., and the quaternary ammonium salt used for modification may be 3-chloro-2-hydroxypropyltrimethylammonium chloride or other quaternary ammonium salt compounds that can react with the natural product.

[0014] The inorganic nanoparticles in step (3) are nanoparticles with antibacterial properties, and may be silver nanoparticles or CuO nanoparticles.

[0015] The pH of the solution in step (4) can be adjusted by using NaOH solution, or by using weak base triethylamine, pyridine or sodium carbonate. In order to increase the reaction speed, the reaction can be heated appropriately, generally not exceeding 50°C.

[0016] The distilled water immersion time in step (5) is generally not less than 48 hours, and the water is frequently changed to remove uncrosslinked components.

[0017] The present invention first synthesizes a hydrophilic polymer containing an amino group and an acid anhydride, and then forms a hydrogel in situ in water through the reaction between the amino group and the acid anhydride. The reaction conforms to the characteristics of a click reaction, does not require a catalyst, and can be carried out quickly in water; the amino group and the acid anhydride react to produce a carboxyl group, which can give the gel pH sensitivity. The natural macromolecule modified with a quaternary ammonium salt is used to give the hydrogel antibacterial properties. In the process of preparing the semi-interpenetrating network hydrogel, the antibacterial properties of the gel can also be increased by in situ addition of inorganic nanoparticles. The "one-pot method" is used to prepare the semi-interpenetrating network antibacterial aerogel based on natural macromolecules, which has a simple operation process, a short reaction time, and a wide range of application prospects.

[0018] The present invention is described in detail below with reference to the examples. However, it should be understood that the following examples are only illustrative of the embodiments of the present invention, and are not intended to limit the scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 Infrared spectra of semi-IPN gels prepared by changing the total mass concentration of the solution

[0020] Figure 2Gel mass fraction (left) and swelling degree (right) of gels prepared by changing the molar ratio of acrylamide / maleic anhydride

[0021] Figure 3 Gel mass fraction (left) and swelling degree (right) of gel when changing the quaternary ammonium salt content

[0022] Figure 4 The swelling degree curve of semi-IPN hydrogel as a function of pH (left) and the cyclic curve of swelling degree (right) DETAILED DESCRIPTION

[0023] Example 1

[0024] Add appropriate amount of maleic anhydride, acrylamide, azobisisobutyronitrile and 60 mL 1,4-dioxane in a single-necked flask, stir and dissolve at room temperature, then evacuate and fill with nitrogen. After 3-4 cycles, heat to 75°C, stir and react for 8 h, filter and obtain a white solid, which is vacuum dried at 70°C for 12 h. The total monomer concentration is controlled to be 1 mol·L -1 , AIBN concentration was controlled at 0.005 mol·L -1 By controlling the molar ratio of acrylamide to maleic anhydride, copolymers of different compositions can be obtained. Similarly, by replacing maleic anhydride with itaconic anhydride, copolymers of itaconic anhydride and acrylamide can be obtained.

[0025] Example 2

[0026] Add appropriate amount of maleic anhydride, N,N-dimethylacrylamide, azobisisobutyronitrile and 60 mL1,4-dioxane in a single-necked flask, stir and dissolve at room temperature, then evacuate and fill with nitrogen. After 3-4 cycles, heat to 75°C, stir and react for 8 h, cool, precipitate with petroleum ether, filter and obtain a white solid, which is vacuum dried at 75°C for 12 h. The total monomer concentration is controlled to be 1 mol·L -1 , AIBN concentration was controlled at 0.005 mol·L -1 By controlling the molar ratio of N,N-dimethylacrylamide to maleic anhydride, copolymers with different compositions can be obtained.

[0027] Example 3

[0028] In a three-necked flask, 6.4809 g N-propylacrylamide, 0.8024 g maleic anhydride, 1.7446 g acrylamide, 0.0738 g azobisisobutyronitrile (AIBN) were added in sequence, and then 60 mL of 1,4-dioxane was added. After stirring and dissolving at room temperature, vacuuming and nitrogen filling were started. After 3-4 cycles, the temperature was stopped, and heating was started. The temperature was raised to 75°C and stirred for 8 h. The reaction was naturally cooled to room temperature. A white substance was precipitated, and it was filtered to obtain a white solid, which was vacuum dried at 60°C for 12 hours. A terpolymer with a molar ratio of N-isopropylacrylamide: acrylamide: maleic anhydride of 7:3:1 was obtained.

[0029] Example 4

[0030] With anhydrous ethanol as the reaction solvent, first add n-butylamine and stir, then add 0.055 g of halloysite nanotubes, and finally add 0.0849 g of silver nitrate (silver nitrate and n-butylamine in a molar ratio of 1: 0.5) and stir rapidly for 10 min, then put it in a 50°C oil bath to react for 50 min, finally stand and separate the supernatant, wash the obtained sample with anhydrous ethanol, and vacuum dry it at 60°C for 24 h to obtain a gray-black sample, which is the nanoparticles loaded with silver ions.

[0031] Example 5

[0032] Dissolve 0.1961 g NaOH in 40 mL distilled water, then add 1.0000 g carboxyl chitosan, and then add 2.23 g 2,3-epoxypropyltrimethylammonium chloride. After dissolution, stir and react at 50°C for 6 h. After the reaction, put the reaction solution into a dialysis bag, dialyze with deionized water for 3 days, and then freeze-dry to obtain quaternary ammonium salt carboxymethyl chitosan.

[0033] Example 6

[0034] Accurately weigh 2.00 g of cellulose cotton linter pulp and place it in a 250 mL beaker. Add NaOH, CO(NH 2)2 The mixed solution of cellulose and H2O (mass ratio 6:15:79) was mechanically stirred for 5 min and then placed in a -12℃ refrigerator for 12 hours. After thawing at room temperature, it was mechanically stirred until a homogeneous solution was formed. Then 5.89 g of etherifying agent (3-chloro-2-hydroxypropyltrimethylammonium chloride) was added to the above cellulose solution and reacted at 25℃ for 24 h to cause quaternization reaction of cellulose units under the action of the etherifying agent to generate cellulose quaternary ammonium salt.

[0035] Example 7

[0036] First, 0.0333 g of cellulose quaternary ammonium salt was dissolved in 2 mL of water, and then 0.1316 g of a binary copolymer with a molar ratio of acrylamide to maleic anhydride of 6:1 was added. At the same time, 0.1179 g of polyacrylamine hydrochloride was dissolved in 1 mL of water. The pH of the solution was adjusted to > 7 with an aqueous NaOH solution. The two solutions were mixed and gelled at 25°C. The gel mass fraction was 80.50% and the swelling degree was 1690.19%.

[0037] Example 8

[0038] First, 0.0200 g of cellulose quaternary ammonium salt was dissolved in 2 mL of water, and then 0.0790 g of a binary copolymer with a molar ratio of acrylamide to maleic anhydride of 6:1 was added. At the same time, 0.0707 g of polyacrylamine hydrochloride was dissolved in 1 mL of water. The pH of the solution was adjusted to > 7 with NaOH aqueous solution. The two solutions were mixed and gelation occurred at 25°C. The gel mass fraction was 86.91% and the swelling degree was 1342.73%.

[0039] Example 9

[0040] First, 0.0166 g of chitosan quaternary ammonium salt was dissolved in 2 mL of water, and then 0.0759 g of a ternary copolymer with a molar ratio of N-isopropylacrylamide, acrylamide and maleic anhydride of 7:3:1 was added. At the same time, 0.0741 g of polyacrylamine hydrochloride was dissolved in 1 mL of water. The pH of the solution was adjusted to >7 with NaOH aqueous solution. The two solutions were mixed and gelled at 30°C for 30 min. The gel mass fraction was 69.00% and the swelling degree was 4564.09%.

[0041] Example 10

[0042] First, 0.0500 g of chitosan quaternary ammonium salt was dissolved in 2 mL of water, and then 0.0759 g of a terpolymer of N-isopropylacrylamide, acrylamide and maleic anhydride with a molar ratio of 7:3:1 was added. At the same time, 0.0741 g of polyacrylamine hydrochloride was dissolved in 1 mL of water. The pH of the solution was adjusted to >7 with NaOH aqueous solution. The two solutions were mixed and gelled at 30°C for 30 min. The gel mass fraction was 84.60% and the swelling degree was 1160.41%.

[0043] Embodiment 11

[0044] First, 0.0333 g of cellulose quaternary ammonium salt was dissolved in 2 mL of water, and then 0.05 g of halloysite-loaded silver ion nanoparticles and 0.1488 g of acrylamide-maleic anhydride copolymer (molar ratio of 8:1) were added. At the same time, 0.1059 g of polyacrylamine hydrochloride was dissolved in 1 mL of water. The pH of the solution was adjusted to > 7 with NaOH aqueous solution. The two solutions were mixed and gelled at 25°C.

Claims

1. A method for preparing a semi-interpenetrating network aerogel with antibacterial properties through a click reaction between amino groups and anhydrides in water, characterized in that: The method comprises the following steps: 1) Modification of cellulose or chitosan with quaternary ammonium compounds; 2) synthesizing a water-soluble polymer containing anhydride and a water-soluble polymer containing amino group respectively; 3) Dispersing a water-soluble polymer containing amino groups, a water-soluble polymer containing anhydride, quaternary ammonium salt-modified cellulose or quaternary ammonium salt-modified chitosan, and inorganic nanoparticles with antibacterial properties in water, adding a small amount of NaOH aqueous solution to adjust the solution pH to > 7, heating, and gelation occurs through a click reaction between amino groups and anhydride to form a semi-interpenetrating network hydrogel; 4) The semi-IPN hydrogel prepared in step (3) is placed in distilled water to remove impurities remaining in the hydrophilic network hydrogel, and then freeze-dried to obtain an aerogel.

2. The preparation method according to claim 1, characterized in that The water-soluble polymer containing amino groups is polyacrylamine hydrochloride or polylysine; the water-soluble polymer containing acid anhydride is a copolymer of maleic anhydride or itaconic anhydride and one or more of acrylamide, N-isopropylacrylamide, and N, N-dimethylacrylamide.

3. The preparation method according to claim 1, characterized in that: The heating reaction temperature in step (3) is controlled at 18-50°C, and the reaction time is 0.1-10 minutes.

4. The preparation method according to claim 1, wherein the quaternary ammonium salt used in step (1) is 3-chloro-2-hydroxypropyltrimethylammonium chloride or 2,3-epoxypropyltrimethylammonium chloride.

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