A pH / temperature dual-sensitive interpenetrating network hydrogel and preparation method thereof

Abstract

The invention discloses a method for preparing a pH / temperature dual-sensitive interpenetrating network hydrogel by a "one-pot method" of anhydride-amino click reaction and free radical polymerization in an aqueous phase, comprising the following steps: first, dissolving an amino-containing polymer, anhydride-containing copolymer, a temperature-sensitive monomer, a crosslinking agent, and an initiator in water, using anhydride-amino click reaction to obtain a first polymer network (pH-sensitive network), and forming a second network (temperature-sensitive network) by free polymerization, thereby obtaining a dual-sensitive interpenetrating network hydrogel. The invention has a simple preparation process, mild conditions, and a fast reaction speed. The obtained pH / temperature-sensitive interpenetrating network hydrogel combines the excellent properties of the two networks 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 pH / temperature dual-sensitive interpenetrating network hydrogel by a "one-pot method" of utilizing anhydride-amino click reaction and free radical polymerization. Background Art

[0002] Hydrogels are hydrophilic polymer networks that can swell but not dissolve in water. Due to the special properties of hydrogels, hydrogels have broad application prospects in biomedicine, water treatment, agriculture, construction, etc. Smart hydrogels are hydrogels that can respond to environmental stimuli (temperature, pH, electric field, magnetic field, chemicals, etc.). Among them, temperature and pH are common environmental changes in organisms and in nature. It is of great significance to study pH / temperature dual-sensitive smart hydrogels. However, the performance of traditional hydrogels often cannot meet the requirements of applications. For this reason, material scientists have proposed many methods for hydrogel modification. The preparation of interpenetrating network hydrogels is a common method for hydrogel modification. Interpenetrating network hydrogels are interwoven polymers formed by two or more cross-linked hydrophilic polymers penetrating each other. The interaction between the components in the network often produces a synergistic effect, making its performance better than that of a single polymer network. Interpenetrating network hydrogels prepared by different methods show different properties. It is very important to choose a suitable method when preparing interpenetrating network hydrogels. Scientists have made many interesting explorations in this regard. Using click reactions to prepare hydrogels is a new technology with broad application prospects. Click reaction is a general term for a class of reactions that are characterized by modular reaction, rapidity, high efficiency, and mild conditions, including carbon-carbon multiple bond addition reactions, nucleophilic ring-opening reactions, etc., and there are no clear boundaries between them. At present, the types of click reactions are constantly expanding, such as reactions between amino-aldehyde groups, thiol-isocyanate groups, and amino-epoxy groups are also classified as click reactions. The traditional azide-alkyne Husigen cycloaddition click reaction has the advantages of mild conditions, strong selectivity, and high yield, but the copper catalyst will remain in the product, thereby affecting the biocompatibility of the hydrogel. Therefore, it is of great significance to develop a click reaction that does not require a catalyst or initiator and does not require an organic solvent to prepare hydrogels. Summary of the invention

[0003] The purpose of the present invention is to prepare a pH / temperature dual-sensitive interpenetrating network hydrogel by combining anhydride-amino click reaction with free radical polymerization to overcome the problems existing in the preparation and application of traditional hydrogels. The method adopts a "one-pot method" to prepare a pH / temperature dual-sensitive interpenetrating network hydrogel by anhydride-amino click reaction and free radical polymerization in an aqueous phase, which is simple to operate, mild in conditions, short in reaction time, and green and environmentally friendly.

[0004] To achieve the above object, the present invention adopts the following technical solutions:

[0005] (1) dissolving a polymer containing anhydride and amino group, a thermosensitive monomer, a crosslinking agent, and a photoinitiator in water to form a homogeneous solution;

[0006] (2) Add a small amount of alkali to adjust the pH of the solution to >7, and form an interpenetrating network hydrogel through anhydride-amino click reaction and free radical polymerization at room temperature or under heating;

[0007] (3) placing the prepared interpenetrating network hydrogel in distilled water to remove impurities remaining in the hydrophilic network hydrogel, and freeze-drying or vacuum-drying to obtain the interpenetrating network hydrogel;

[0008] In the step (1), a polymer containing amino groups and anhydrides is synthesized by a general method. The polymer containing amino groups can be a hyperbranched polymer or a linear polymer, and can be either an amino group or an amino group's hydrochloride. The polymer containing anhydrides can be prepared by polymerizing maleic anhydride or other polymerizable anhydrides with different monomers, and can be a binary copolymer or a multi-component copolymer.

[0009] The monomer used in step (1) may be one or more of N-isopropylacrylamide, (meth)acrylic acid, 2-acrylamido-2-methylpropanesulfonic acid and the like, at least one of which is a temperature-sensitive monomer; the crosslinking agent used may be a water-soluble compound containing multiple double bonds such as N,N-methylenebisacrylamide and polyethylene glycol di(meth)acrylate. The photoinitiator is preferably 2,2-dimethoxy-2-phenylacetophenone. The redox initiation system used may be a system such as potassium persulfate-ascorbic acid, ammonium persulfate-sodium bisulfite and the like.

[0010] The pH of the solution in step (2) can be adjusted by using NaOH solution, or by using weak base triethylamine, 4-dimethylaminopyridine, pyridine or sodium carbonate. In order to increase the reaction speed, the reaction can be heated appropriately, generally not exceeding 60°C.

[0011] The reaction time in step (2) can be adjusted according to the reaction conditions. If the reaction temperature is low, the reaction time can be prolonged; if photopolymerization is used, the reaction time can be shortened; and increasing the pH of the solution can also shorten the reaction time.

[0012] The soaking time in distilled water in step (3) is generally not less than 48 hours, and the water is frequently changed to facilitate the removal of impurities such as residual monomers.

[0013] The technical advantages of the present invention are mainly reflected in:

[0014] The present invention first synthesizes a hydrophilic polymer containing an amino group and an acid anhydride, and then prepares a hydrogel 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 gives the hydrogel pH sensitivity. The polymer is prepared by photopolymerization or a redox initiation system, and the reaction time is short. The properties of the polymer can be adjusted by controlling the feed ratio of the monomers, and the hydrogel can be given temperature sensitivity by selecting a temperature-sensitive monomer. The "one-pot method" is used to prepare a pH / temperature dual-sensitive interpenetrating network hydrogel, which is simple to operate, mild in conditions, short in reaction time, and green and environmentally friendly, and has broad application prospects.

[0015] 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

[0016] Figure 1 Swelling curve of interpenetrating network hydrogel (left) and gel mass fraction (right)

[0017] Figure 2 Temperature (left), pH (right) reversibility and repeatability of the swelling behavior of interpenetrating network hydrogels

[0018] Figure 3 FTIR spectrum (left) and SEM image (right) of interpenetrating network hydrogel

[0019] Figure 4 Release curves of isoniazid from interpenetrating network hydrogel at different temperatures (left) and different pH (right) DETAILED DESCRIPTION

[0020] Example 1

[0021] 0.3717 g binary copolymer, 0.02828 g polylysine, 0.1132 g N-isopropylacrylamide, 1.54×10 -3 g N,N-methylenebisacrylamide, 30 μL triethylamine, 2.70×10 -3 g potassium persulfate, 1.76×10 -3 g ascorbic acid were added into 2 mL water in a certain order and reacted at room temperature for 1 hour to obtain an interpenetrating network hydrogel with a gel mass fraction of 62.42% and a swelling degree of 17.15%.

[0022] Example 2

[0023] 0.3471 g binary copolymer, 0.05282 g polylysine, 0.1132 g N-isopropylacrylamide, 1.54×10 -3g N,N-methylenebisacrylamide, 40 μL triethylamine, 2.70×10 -3 g potassium persulfate, 1.76×10 -3 g ascorbic acid were added into 2 mL water in a certain order and reacted at room temperature for 1 hour to obtain an interpenetrating network hydrogel with a gel mass fraction of 65.35% and a swelling degree of 2465%.

[0024] Example 3

[0025] 0.3257 g binary copolymer, 0.0743 g polylysine, 0.1132 g N-isopropylacrylamide, 1.54×10 -3 g N,N-methylenebisacrylamide, 50 μL triethylamine, 2.70×10 -3 g potassium persulfate, 1.76×10 -3 g ascorbic acid were added into 2 mL water in a certain order and reacted at room temperature for 1 hour to obtain an interpenetrating network hydrogel with a gel mass fraction of 67.22% and a swelling degree of 36.16%.

[0026] Example 4

[0027] 0.3257 g binary copolymer, 0.0743 g polylysine, 0.1132 g N-isopropylacrylamide, 1.54×10 -3 g N,N-methylenebisacrylamide, 50 μL triethylamine, 2.70×10 -3 g potassium persulfate, 1.76×10 -3 g ascorbic acid were added into 2 mL water in a certain order and reacted in a 50 ℃ water bath for 5 minutes to obtain an interpenetrating network hydrogel with a gel mass fraction of 68.47% and a swelling degree of 4389%.

[0028] Example 5

[0029] 0.3717 g binary copolymer, 0.02828 g polylysine, 0.1132 g N-isopropylacrylamide, 1.03×10 -3 g N,N-methylenebisacrylamide, 30 μL triethylamine, 2.70×10 -3 g potassium persulfate, 1.76×10 -3 g ascorbic acid were added into 2 mL water in a certain order and reacted in a 50 ℃ water bath for 5 minutes to obtain an interpenetrating network hydrogel with a gel mass fraction of 55.17% and a swelling degree of 1888%.

[0030] Example 6

[0031] 0.130 g of polyacrylamine hydrochloride, 0.113 g of N-isopropylacrylamide, 0.207 g of 2-acrylamido-2-methylpropanesulfonic acid, 0.24 g of cross-linking agent polyethylene glycol dimethacrylate, 0.147 g of PMA, 0.08 mL of photoinitiator solution, and 3 mL of water were added into a test tube in a certain order, the pH value of the solution was adjusted in the middle, and the test tube was heated and illuminated after mixing evenly to obtain an interpenetrating network hydrogel with a gel mass fraction of 62% and an equilibrium swelling degree of 376%.

[0032] Example 7

[0033] 0.200 g of polyacrylamine hydrochloride, 0.113 g of N-isopropylacrylamide, 0.207 g of 2-acrylamido-2-methylpropanesulfonic acid, 0.24 g of cross-linking agent polyethylene glycol dimethacrylate, 0.224 g of PMA, 0.08 mL of photoinitiator solution, and 3 mL of water were added to a test tube in a certain order, the pH value of the solution was adjusted in the middle, and the test tube was heated and illuminated after mixing evenly to obtain an interpenetrating network hydrogel with a gel mass fraction of 66% and an equilibrium swelling degree of 250%.

[0034] Example 8

[0035] 0.130 g of polyacrylamine hydrochloride, 0.113 g of N-isopropylacrylamide, 0.207 g of 2-acrylamido-2-methylpropanesulfonic acid, 0.24 g of cross-linking agent polyethylene glycol dimethacrylate, 0.145 g of PMA, 0.08 mL of photoinitiator solution, and 3 mL of water were added to a test tube in a certain order, the pH value of the solution was adjusted in the middle, and the test tube was heated and illuminated after mixing evenly to obtain an interpenetrating network hydrogel with a gel mass fraction of 58% and an equilibrium swelling degree of 363%.

Claims

1. A method for preparing pH / temperature dual-sensitive interpenetrating network hydrogel by a "one-pot" method of anhydride-amino click reaction and free radical polymerization in an aqueous phase, It is characterized in that The method comprises the following steps: 1) dissolving an anhydride-containing polymer, an amino-containing polymer, a monomer, a crosslinking agent, and an initiator in water, wherein the monomer used is one or more of N-isopropylacrylamide, methacrylic acid, 2-acrylamido-2-methylpropanesulfonic acid, and N-vinylcaprolactam, at least one of which is a temperature-sensitive monomer; 2) Add a small amount of alkali to adjust the pH of the solution to >7, gelation occurs through anhydride-amino click reaction to form a first network; and a second network is formed through free radical polymerization; 3) Finally, the prepared interpenetrating network hydrogel is placed in distilled water to remove impurities remaining in the hydrophilic network hydrogel, and then freeze-dried or vacuum-dried to obtain a pH / temperature dual-sensitive interpenetrating network hydrogel.

2. The preparation method according to claim 1, It is characterized in that The polymer containing acid anhydride is a binary copolymer or a multi-component copolymer of maleic anhydride and other monomers; the polymer containing amino group is polyethyleneimine or polylysine or polyacrylamine hydrochloride.

3. The preparation method according to claim 1, It is characterized in that The base used in step (2) is aqueous sodium hydroxide solution or triethylamine.

4. The preparation method according to claim 1, It is characterized in that The reaction temperature in step (2) is controlled at 15-60° C., and the reaction time is 0.1-24 hours.

5. The preparation method according to claim 1, wherein the cross-linking agent used is N,N-methylenebisacrylamide or polyethylene glycol dimethacrylate.

6. The preparation method according to claim 1, wherein the free radical polymerization in step (2) is photopolymerization or redox system initiated polymerization, wherein the photoinitiator used for photopolymerization is 2,2-dimethoxy-2-phenylacetophenone; and the redox initiation system used is a potassium persulfate-ascorbic acid system or an ammonium persulfate-sodium bisulfite system.

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