A preparation method of a semi-interpenetrating network hydrogel based on amino-succinimide ring-opening reaction

Abstract

The application discloses a preparation method of a semi-interpenetrating network hydrogel based on an amino-succinimide ring-opening reaction, which comprises the following steps: firstly, a hydrophilic compound containing amino groups, such as trishydroxymethylaminomethane, is used to modify polysuccinimide to obtain water-soluble polysuccinimide polymer; N-vinylcaprolactam and 3-mercaptopropionic acid are reacted to obtain poly-N-vinylcaprolactam polymer with terminal carboxyl groups; and the polymer is used to graft hydroxypropyl methyl cellulose to obtain macromolecular hydroxypropyl methyl cellulose derivative. The water-soluble polysuccinimide, the polymer containing amino groups and the hydroxypropyl methyl cellulose derivative are dissolved in water, and the amino-succinimide ring-opening reaction is utilized to obtain the hydrogel; the hydrogel is soaked in water to remove uncrosslinked components; and after drying, the semi-interpenetrating network hydrogel is obtained. The preparation process is simple, the conditions are mild, and the reaction speed is fast; and the prepared hydrogel has pH / temperature sensitivity and can be used in many fields such as tissue engineering, drug release, water treatment and the like.

Description

Technical Field

[0001] This invention belongs to the field of polymer materials and relates to a method for preparing semi-interpenetrating network hydrogels using an amino-succinimide ring-opening reaction. Technical Background

[0002] Hydrogels are three-dimensional networks formed by hydrophilic polymers that can absorb and hold large amounts of water. Most hydrogels exhibit intelligent responsiveness to external stimuli, such as light, electric fields, temperature, pH, and magnetic fields. These unique properties enable hydrogels to be widely used in tissue engineering, drug delivery, biosensors, and wastewater treatment. Based on their structure, hydrogels can be classified into mono-network hydrogels, semi-interpenetrating network hydrogels, and interpenetrating network hydrogels. Semi-interpenetrating network hydrogels are polymer networks composed of one or more networks and one or more linear or branched polymers, characterized by linear or branched macromolecules permeating into at least one network at the molecular scale. The linear or branched polymers constituting the semi-interpenetrating polymer network can, in principle, separate from the constituent polymer network without breaking chemical bonds. By forming (semi-)interpenetrating networks, the synergistic effect of two or more polymers with different properties can improve the mechanical properties and swelling response of hydrogels, thereby promoting their practical applications.

[0003] Hydrogels can be classified into physically cross-linked hydrogels and chemically cross-linked hydrogels based on their preparation principles. Physical cross-linking typically refers to the process by which polymers form hydrogels through non-covalent bonds. The dynamically tunable physical action endows hydrogels with excellent properties such as self-healing and self-repair, meaning its action is reversible. When external environmental factors such as pH, temperature, and pressure change, the physical cross-linking points are either destroyed or rebuilt. Therefore, physically cross-linked gels are also called reversible gels. Chemical cross-linking refers to the process by which monomers or polymers are linked together by multifunctional cross-linking agents through covalent bonds to form hydrogels. Chemically cross-linked hydrogels have strong bonds, stable network structures, and strong mechanical properties. However, traditional chemical cross-linking requires the introduction of toxic initiators and cross-linking agents, which greatly increases the cytotoxicity of the hydrogel and limits its application in the biomedical field. Therefore, developing cross-linking reactions for preparing hydrogels that do not require catalysts or organic solvents and are simple to operate is of great significance. Summary of the Invention

[0004] The technical problem this invention aims to solve is to provide a method for preparing hydrogels through the ring-opening reaction of amino-succinimide in aqueous solution without the addition of initiators and crosslinking agents, thereby overcoming the problems existing in the preparation and application of traditional chemically crosslinked hydrogels. This method features mild reaction conditions, short reaction time, and is environmentally friendly.

[0005] To solve the above-mentioned technical problems, the present invention provides the following technical solution: (1) Preparation of partially ring-opened water-soluble polysuccinimide; (2) Natural macromolecular cellulose was modified with poly-N-vinylcaprolactam to obtain a temperature-sensitive macromolecular polymer; (3) Dissolve water-soluble polysuccinimide, amino-containing polymer, and polyN-vinylcaprolactam grafted macromolecules in water; (4) Add a small amount of alkali to adjust the pH of the solution to >7, and form a semi-interpenetrating network hydrogel through the ring-opening reaction of amino-succinimide at room temperature; (5) The impurities remaining in the hydrogel network are removed by immersing the prepared semi-interpenetrating network hydrogel in distilled water, and then the pure semi-interpenetrating network hydrogel is obtained by freeze drying or heat drying.

[0006] In step (1), the water-soluble polysuccinimide is obtained by reacting different amino-containing hydrophilic compounds with polysuccinimides of different molecular weights. The hydrophilic compounds used are one or more of tris(hydroxymethyl)aminomethane, aminosulfonic acid, or 3-amino-1,2-propanediol. In step (2), the temperature-sensitive macromolecular polymer is a cellulose derivative, a starch derivative, a sodium alginate derivative, or a synthesized polymer. Temperature-sensitive polymers are obtained by modification with poly(N-vinylcaprolactam) or poly(N-isopropylacrylamide). The polymer containing amino groups in step (3) is a hyperbranched polymer or a linear polymer. It is derived from natural polymers or synthetic polymers.

[0007] In step (4), the pH of the solution is adjusted using NaOH solution or a weak base such as triethylamine, pyridine, or sodium carbonate. If the pH is greater than 7, no alkali needs to be added. To increase the reaction rate, the reaction can be appropriately heated, generally not exceeding 50°C.

[0008] In step (5), the hydrogel is soaked in distilled water for no less than 48 hours, and the water is changed frequently to remove uncrosslinked components.

[0009] The main technical advantages of this invention are as follows: This invention first synthesizes water-soluble polysuccinimide, then dissolves it in water with an amino-containing polymer, and crosslinks it into a gel via an amino-succinimide ring-opening reaction. This reaction is characterized by the absence of catalysts and initiators, mild reaction conditions, and rapid gelation in aqueous solution. The amino-succinimide ring-opening reaction produces carboxyl groups, which impart pH sensitivity to the hydrogel. Temperature-sensitive polymers are selected to modify natural macromolecules, resulting in temperature-sensitive natural macromolecular derivatives. These derivatives are then incorporated into the hydrogel network, giving the hydrogel dual pH / temperature responsiveness. A one-pot method is used to prepare a pH / temperature dual-responsive semi-interpenetrating network hydrogel based on the amino-succinimide ring-opening reaction. This hydrogel preparation method features mild reaction conditions, short reaction time, simple operation, and readily available raw materials, showing broad application prospects in the preparation of (semi)interpenetrating network hydrogels.

[0010] The present invention will be described in detail below with reference to embodiments. However, it should be understood that the following embodiments are merely illustrative examples of implementation of the present invention and are not intended to limit the scope of the present invention. Attached Figure Description

[0011] Figure 1. SEM images of the single-network hydrogel (a) and the semi-interpenetrating network hydrogel (b).

[0012] Figure 2. Gel mass fraction (a) and swelling degree (b) of macromolecules with different temperature sensitivity.

[0013] Figure 3. Equilibrium swelling degree (a) and swelling reversibility (b) of semi-interpenetrating network hydrogels at different temperatures.

[0014] Figure 4. Equilibrium swelling degree (a) and swelling reversibility (b, c) of semi-interpenetrating network hydrogel at different pH values. Detailed Implementation

[0015] Example

[0016] 3.8836 g of polysuccinimide and 2.4228 g of tris(hydroxymethyl)aminomethane were weighed into a 100 mL round-bottom flask, and 60.0 mL of DMF was added. The mixture was magnetically stirred at 60 °C to dissolve the polysuccinimide, and the reaction was carried out under argon protection for 12 h. The resulting solution was added dropwise to 350 mL of diethyl ether solution to precipitate the polysuccinimide. After filtration, a reddish-brown solid was obtained, which was washed three times with diethyl ether and dried under vacuum at 70 °C for 12 h to obtain water-soluble polysuccinimide (PSI-TRIS) with a yield of 5.9911 g, representing a yield of 95%. Example

[0017] Polysuccinimide (1.4564 g), tris(hydroxymethyl)aminomethane (0.6057 g), and 2-furanylamine (0.9712 g) were added to a round-bottom flask containing 30 mL of DMF. The mixture was stirred with a magnetic stirrer until homogeneous. The reaction was carried out at 60 °C for 12 h under an argon atmosphere. After the reaction was complete, the solution was slowly added dropwise to 200 mL of anhydrous diethyl ether, resulting in a yellowish-brown precipitate. The precipitate was filtered and washed with diethyl ether, and the process was repeated three times to remove impurities. The washed and filtered yellowish-brown precipitate was dried under vacuum at 45 °C to constant weight. 1.8814 g of yellowish-brown solid was obtained, with a yield of 62.02%. Example

[0018] First, 0.8075 g of polyethyleneimine and 0.0445 g of temperature-sensitive macromolecules were weighed and dissolved in 2 mL of water, while 50 μL of triethylamine was added. Separately, 0.2083 g of water-soluble succinimide was weighed and dissolved in 1.5 mL of water. The two solutions were then mixed, and gelation occurred at 25°C. The gel mass fraction was 83.43%, and the swelling degree was 652.30%. Example

[0019] First, 1.5170 g of polyethyleneimine and 0.1860 g of temperature-sensitive macromolecules were weighed and dissolved in 1.5 mL of water, while 50 μL of triethylamine was added. Separately, 0.1961 g of water-soluble succinimide was weighed and dissolved in 1.5 mL of water. The two solutions were then mixed, and gelation occurred at 25°C. The gel mass fraction was 82.88%, and the swelling degree was 968.01%. Example

[0020] First, weigh out 1.5170 g of polyethyleneimine and 0.1860 g of temperature-sensitive macromolecules and dissolve them in 1.5 mL of water. Separately, weigh out 0.1961 g of water-soluble succinimide and dissolve it in 1.5 mL of water. Then, mix the two solutions and allow them to gel within 1 minute at 25°C. Example

[0021] First, 1.5170 g of polyethyleneimine was dissolved in 1.5 mL of water, and 50 μL of triethylamine was added simultaneously. Separately, 0.1961 g of water-soluble succinimide was dissolved in 1.5 mL of water. The two solutions were then mixed, and gelation occurred within 1 minute at 25°C, with a gel mass fraction of 82.69% and a swelling degree of 929.46%. Example

[0022] First, weigh 0.2315 g of carboxymethyl chitosan and dissolve it in 1.0 mL of water. Separately, weigh 0.2685 g of water-soluble succinimide and dissolve it in 1.0 mL of water. Then, mix the two solutions and gel at 25°C within 1 minute. The gel mass fraction is 50.30% and the swelling degree is 1807.59%.

Claims

1. A method for preparing a semi-interpenetrating network hydrogel based on the ring-opening reaction of amino-succinimide, characterized in that: The preparation method includes the following steps: 1) Modify polysuccinimide with a hydrophilic compound containing amino groups to obtain water-soluble polysuccinimide; 2) Grafting hydroxypropyl methylcellulose with poly(N-vinylcaprolactam) yields a temperature-sensitive macromolecule; 3) Dissolve water-soluble polysuccinimide, amino-containing polymers, and temperature-sensitive macromolecules in water to obtain a transparent solution; 4) Add a small amount of alkali to adjust the pH of the solution to >7, and crosslink it into a gel through the ring-opening reaction of amino-succinimide to obtain a semi-interpenetrating network hydrogel; 5) The prepared semi-interpenetrating network hydrogel was soaked in distilled water and then dried to remove impurities from the hydrogel network. The hydrophilic compound containing amino groups used in step (1) is tris(hydroxymethyl)aminomethane, p-aminobenzoic acid, 3-amino-1,2-propanediol, or aminosulfonic acid; the amino polymer containing amino groups in step (3) is polyethyleneimine, polylysine, polyacrylamide hydrochloride, or chitosan.

2. The method for preparing a semi-interpenetrating network hydrogel based on the ring-opening reaction of amino-succinimide according to claim 1, characterized in that: In step (4), if the pH of the solution is <7, an alkali is needed to adjust the pH of the solution to >7. The alkali used is strong alkali sodium hydroxide or weak alkali sodium carbonate, triethylamine, or pyridine. The reaction temperature is controlled at 10-50℃ and the reaction time is 0.1-10 minutes.

3. The method for preparing a semi-interpenetrating network hydrogel based on the ring-opening reaction of amino-succinimide according to claim 1, characterized in that: In step (5), the water needs to be changed frequently during the soaking process of the hydrogel to remove the uncrosslinked components. The drying method is freeze drying or heat drying.

Images