CN101280094A - Bioactive hydrogel-conductive polymer nanocomposite material and its synthesis method - Google Patents

Abstract

Biologically active hydrogel-conductive polymer nanocomposite material and synthesis method, relating to a bioactive material, first synthesize polyethylene glycol and hydroxy acid under the catalysis of octoate tin to obtain ethylene glycol-hydroxy acid block copolymer ; The copolymer reacts with acryloyl chloride and triethylamine to obtain an acrylic acid group-terminated ethylene glycol-hydroxy acid block copolymer; the above-mentioned copolymer is dissolved in water and obtained by photo-induced crosslinking or free radical crosslinking Gel; finally, the gel is swollen with pyrrole or aniline monomer solution, and polymerized under the action of an initiator to obtain a nanocomposite material of ethylene glycol-hydroxy acid block copolymer and polypyrrole or polyaniline. By copolymerizing PEG with hydroxy acid, the gel system is endowed with biodegradability; and the honeycomb hole of the hydrogel membrane material provides a composite space for the conductive polymer; and the biological activity of polypyrrole and polyaniline, and the hydrogel After the glue is compounded, it can impart biological activity and at the same time have a nano-reinforcement effect on the gel system.

Description

Bioactive hydrogel-conductive polymer nanocomposite material and its synthesis method

technical field

The invention relates to a nanocomposite material, in particular to a biodegradable bioactive hydrogel-conductive polymer nanocomposite material and a synthesis method thereof.

Background technique

Professor Hench, the inventor of bioglass, clearly pointed out in Science magazine (Hench L L, Polak J M.Science, 2002, 295: 1014-1017) that the third generation of biological materials will not be biologically inert materials, nor are they simply bioavailable. It is not a degradable material, but a bioactive material with both degradability and tissue cell-inducing activity. The high water content of the hydrogel is conducive to the diffusion supply of nutrients and oxygen and the discharge of waste generated by cells; in the biological environment, the interfacial tension is low and the biocompatibility is good; and it can be changed by external environmental signals, such as pH value, Ionic strength, temperature, electrical signal, etc. control the volume change; in addition, the mechanical properties can be adjusted to make it similar to soft tissue. Therefore, in the field of biomedicine, hydrogels are used as drug release carriers, cartilage scaffolds, extracellular matrix, biosensors, and contact lenses. etc. show great application prospects. Biopolymer hydrogels include natural polymers and synthetic polymers, such as collagen, fibrin, hyaluronic acid, sodium alginate, chitosan and other natural polymers, while synthetic polymers polylactic acid (PLA), polyglycolic acid (PGA), polyethylene glycol (PEG), PLA-co-PEG, polyoxyethylene-polyoxypropylene-polyoxyethylene triblock copolymer (Zhang Yan, Shao Fangke, Wu Wei, Yang Wuli, Fu Shou Wide, Polymer Bulletin, 2007, (10): 34-40) etc. various copolymers are several gel materials (Yu G H, Fan Y B.Journal of Biomaterials Science, Polymer Edition, 2008, 19(1):87-98). Leong et al. (Li Q, Wang J, Shahani S, Sun D D N, Sharma B, Elisseeff J H, Leong K W. Biomaterials, 2006, 27:1027-1034) synthesized a biodegradable acrylic acid group The polyphosphate is cross-linked by light to form a gel, which is used as a scaffold material for bone marrow mesenchymal cell culture. Grinstaff et al. (Sontjens S H M, Nettles DL, Carnahan M A, Setton L A, Grinstaff M W. Biomacromolecules, 2006, 7: 310-316) synthesized PEG as the core, obtained by polycondensation of glycerol and succinic acid The dendritic macromolecule is capped with methyl methacrylate at the periphery and cross-linked to form a gel, which is used as a scaffold material for cartilage tissue repair. Zhang Xiufang et al. (Zhu Lin, Liu Haixia, Gong Yandao, Zhao Nanming, Zhang Xiufang. China Tissue Engineering Research and Clinical Rehabilitation, 2007, 11(48): 9650-9654) used the composite hydrogel of sodium alginate and gelatin as a scaffold for Articular cartilage repair. Yu Bin et al. (Yu Bin, Gao Chengjie, Wang Zhizhong, Su Xiuyun, Yang Jiancheng, Chinese Journal of Traumatology and Orthopedics, 2005, 7(5): 435-436) modified polylactic acid-glycolic acid gel with alcohol and calcium alginate to improve Its hydrophilicity and mechanical strength. However, as a bioactive material, hydrogel has to solve several problems: (1) Although the gel material is easy to seed cells, if there are no interconnected pores inside, it is not conducive to the cells inside the material to obtain nutrients; (2) as a scaffold For materials, degradability and biocompatibility are two important performance requirements. Although natural polymers have good biocompatibility, they have the disadvantages of poor mechanical properties and difficult processing and molding. Synthesizing biodegradable and biocompatible polymer hydrogels with good mechanical strength and microporous penetrating structure is an important research direction for scholars. Ethylene glycol-hydroxy acid block copolymers are rich in hydroxyl groups, and it is easy to introduce other polymerizable functional groups through hydroxyl groups to form a gel system and improve mechanical strength. Hydroxy acid is biodegradable, which can endow the block copolymer with Biodegradability. After the gel is formed, adding an easy-to-low-boiling-point solvent for dehydration is beneficial to the fixation of the gel scaffold and the formation of a penetrating microporous structure.

Conductive polymers, such as polypyrrole (Polypyrrole, PPy), polyaniline (Polyaniline, PAn), polythiophene (Polythiophene, PTh), etc. have good biocompatibility, cell-inducing activity, and their rich electrochemical activity, through Electrical stimulation can change cell activity; PPy is favored by researchers for its low toxicity and biological safety. When the conductive polymer is in the nano state, various activities can be enhanced (Abidian MR, Kim D H, Martin D C. Adv. Mater, 2006, 18: 405-409). A series of new bioactive materials can be designed by combining conductive polymers with hydrogels. Martin (Kim D H, Abidian M, Martin D C. Journal of Biomedical Materials Research Part A, 2004, 71A(4): 577-585; Kim D H, Richardson-Burns S M, Hendricks J L, Sequera C, Martin D C, Adv.Funct.Mater, 2007, 17:79-86) has done a lot of work on the application of conductive polymer/hydrogel composite system in nerve tissue engineering and drug release, mainly synthesizing PPy, poly(3, 4-ethylenedioxythiophene) (PEDOT) and sodium alginate, polylactide (PLLA) or lactide-ethylene glycol copolymer hydrogel composite material, applied to the scaffold on the central nervous system repair probe Material. Lira et al. (Lira L M, Cordoba de Torresi S I. Electrochemistry Communications, 2005, 7: 717-723) synthesized polyacrylamide hydrogel-PAn interpenetrating network by electrochemical polymerization, and used it to control drug potential freed.

Contents of the invention

The purpose of the present invention is to provide a biodegradable bioactive hydrogel-conductive polymer nanocomposite material and a synthesis method.

The bioactive hydrogel-conductive polymer nanocomposite material of the present invention is a composite material of ethylene glycol-hydroxy acid block copolymer and polypyrrole or polyaniline, and by mass percentage, the conductive polymer polypyrrole or polyaniline Aniline accounts for 7% to 50% of the total mass of the composite material.

Wherein said hydroxy acid is lactic acid, glycolide, butyrolactone, valerolactone or caprolactone and the like.

The synthesis method of the bioactive hydrogel-conductive polymer nanocomposite of the present invention comprises the following steps:

1) Synthesis of ethylene glycol-hydroxy acid block copolymer

Under the protection of nitrogen, mix polyethylene glycol (PEG) with hydroxyacid, the molar ratio of hydroxyacid to PEG is 2-10, according to mass percentage, then add 0.05%-0.1% tin octoate catalyst of the total system, and vacuumize , raise the temperature to 190-210°C and stir, lower the temperature to 150-170°C to continue the stirring reaction, cool to room temperature to obtain ethylene glycol-hydroxy acid block copolymer, dissolve the product in dichloroethane, and precipitate with anhydrous ether, Filter and dry to obtain purified ethylene glycol-hydroxy acid block copolymer;

2) Synthesis of acrylic acid-terminated ethylene glycol-hydroxy acid block copolymers

Take the above-mentioned purified ethylene glycol-hydroxy acid block copolymer and dissolve it in dichloromethane, the concentration is 10%～14% by mass percentage, cool to 0～5°C in an ice bath, molar ratio, in anhydrous Add acryloyl chloride with a concentration of 0.5-0.83 mol and triethylamine with a concentration of 0.33-0.67 mol under anaerobic conditions, stir and react at 0-5°C for 10-18 hours, then stir and react at room temperature for 12-18 hours, and filter out Triethylamine hydrochloride, add excess dry diethyl ether to the filtrate to obtain acrylic acid group-terminated ethylene glycol-hydroxy acid block copolymer, acrylic acid group-terminated ethylene glycol-hydroxy acid block copolymer The product was dissolved in dichloromethane, purified by hexane precipitation, and dried;

3) Synthesis of cross-linked gel

dissolving the ethylene glycol-hydroxy acid block copolymer terminated by the acrylic acid group in water, and obtaining a gel by photo-initiated cross-linking or free radical cross-linking;

4) In-situ polymerization of pyrrole or aniline monomer

The gel obtained in step 3) is dried, soaked and swollen in an aqueous solution of pyrrole or aniline hydrochloric acid with a pH of 3 to 7 and a monomer concentration of 5 to 50 mmol/L, and then the gel swollen by the monomer solution is placed In the initiator solution, stirred in an ice bath to room temperature, the monomers are polymerized in the gel cross-linked network system to form an interpenetrating network system, filtered, washed with water, dried, and then subjected to water swelling-ethanol dehydration cycle to remove impurities. After drying, a nanocomposite material of ethylene glycol-hydroxy acid block copolymer and polypyrrole or polyaniline is obtained.

The molecular weight of the polyethylene glycol is preferably 200-1000.

In step 3), the initiator is an 18%-25% aqueous solution of ammonium persulfate, potassium persulfate or ammonium persulfate-sodium sulfite; wherein the molar ratio of ammonium persulfate to sodium sulfite is 1:1.

The photo-initiated crosslinking is obtained by taking the above-mentioned acrylic group-terminated ethylene glycol-hydroxy acid block copolymer to form an acrylic group-terminated ethylene glycol-hydroxy acid block copolymer with a mass percentage concentration of 18% to 25%. Aqueous solution A of segment copolymer, photoinitiator 2,2-dimethyl-2-diphenylacetophenone is dissolved in N-vinylpyrrolidone and is made into solution B of 0.3g/mL, solution A and solution B Mix according to the volume ratio of 1000: (2-5), use light radiation for 20-60s to initiate cross-linking, add excess ethanol for dehydration, and then go through water swelling-ethanol dehydration cycle to remove impurities and finally dry.

The free radical crosslinking is to take the ethylene glycol-hydroxy acid block copolymer terminated by the acrylic acid group to prepare the ethylene glycol-hydroxy acid block with a concentration of 18% to 25% by mass percentage. Copolymer aqueous solution, neutralized with KOH to pH 6-7, adding initiator solution and mixing, after mixing, the mass percentage of copolymer and initiator is 100: (1-5), placed in an oven at 70-90°C, and initiated Cross-linking polymerization, adding excess ethanol to quickly dehydrate, and then go through water swelling-ethanol dehydration cycle to remove impurities, and finally dry.

In step 4), the initiator is ammonium persulfate or ferric chloride, etc., wherein the monomer concentration and the initiator concentration are 1: (1-3) in molar ratio.

The nanocomposite material of ethylene glycol-hydroxyacid block copolymer synthesized by the present invention and polypyrrole, polyaniline has the following advantages: (1) PEG has abundant terminal hydroxyl groups, is easy to react with other functional groups, and by adjusting PEG molecular weight difference And the equivalent ratio between PEG and hydroxy acid can control the sequence structure of the block copolymer; (2) PEG itself is not degradable, after copolymerization with hydroxy acid, the biodegradability of hydroxy acid such as lactic acid endows the gel system with biodegradability Degradability; (3) The use of photopolymerization crosslinking is beneficial to the in-situ crosslinking of polymer precursor aqueous solution, which can be used to prepare injectable hydrogels. The product geometry is easy to control, and the curing time is short at room temperature or physiological temperature. The heat is low; (4) Add ethanol to dehydrate quickly after the block copolymer is cross-linked to form a gel, which is beneficial to the fixation of the gel scaffold and the formation of a penetrating microporous structure; (5) Polypyrrole and polyaniline have biological activity, After the gel is compounded, it can impart biological activity and at the same time have a nano-reinforcement effect on the gel system.

Description of drawings

Fig. 1 is the FTIR spectrum of polyaniline and PEG-lactic acid block copolymer composite material in embodiment 1. In Fig. 1, the abscissa is Wavenumbers/cm ^-1 .

Fig. 2 is the FTIR spectrogram of PEG and glycolide in embodiment 2. In Fig. 2, the abscissa is Wavenumbers/cm ^-1 .

Figure 3 is the SEM photo of ethylene glycol-hydroxy acid block copolymer hydrogel film, where A is ethylene glycol-lactic acid, B is ethylene glycol-glycolide, and C is ethylene glycol-ε-caprolactone Esters, D is ethylene glycol-δ-valerolactone, E is ethylene glycol-γ-butyrolactone

Detailed ways

The present invention will be described in further detail below by way of examples.

Embodiment 1: Synthesis of ethylene glycol-lactic acid block copolymer gel and polyaniline nanocomposite:

(1) Synthesis of ethylene glycol-lactic acid block copolymer:

Get 10g PEG (number-average molecular weight 200) and 36gdl-lactic acid under nitrogen protection, and the tin octoate of 23mg is added in the three-neck round bottom flask of 100ml. The reaction mixture was stirred under vacuum at 200°C for 4h, then lowered to 160°C, continued to stir for 2h, and finally cooled to room temperature to obtain an ethylene glycol-lactic acid block copolymer, which was dissolved in dichloroethane and used without Precipitate with water and ether, filter and dry to obtain a purified ethylene glycol-lactic acid block copolymer. From the SEM photo of Figure 3A, it can be seen that the synthesized hydrogel membrane material exhibits a honeycomb shape, and these penetrating holes provide a composite space for the conductive polymer.

(2) Synthesis of ethylene glycol-lactic acid block copolymer terminated by acrylic acid:

Take 30g of the above-mentioned copolymer and dissolve it in 270ml of dichloromethane, place it in a 500mL round bottom flask, cool it to 0°C in an ice bath, replace the reaction bottle with nitrogen three times to obtain an anhydrous and oxygen-free environment, and add 13.9 mL of triethylamine and 16.2 mL of acryloyl chloride were stirred at 0° C. for 12 h, and then at room temperature for 12 h. Remove triethylamine hydrochloride by filtration, and then add excess dry diethyl ether to the filtrate to obtain an acrylic acid group-terminated ethylene glycol-lactic acid block copolymer. It was dissolved in dichloromethane and purified once by hexane precipitation. Finally, it was dried under vacuum at 70°C for 24 hours.

(3) Synthesis of cross-linked gel system: Take 100ml of 20% aqueous solution of the above-mentioned block copolymer, add 0.5ml of 0.3g/mL 2,2-dimethyl-2-diphenylacetophenone N-ethylene base pyrrolidone solution. As for a glass Petri dish, cross-linking was initiated by irradiation with an argon-ion UV laser for 30 s. Add excess ethanol to quickly dehydrate, and then go through two water swelling-ethanol dehydration cycles to remove impurities. Placed at 60°C for 24 hours in vacuum.

(4) In situ polymerization of aniline

Cut 5g of the above dry gel, soak it in 10mmol/L aniline aqueous solution at room temperature for 30min, adjust the pH to 5 with HCl, then place the swollen gel in 20mmol/L ammonium persulfate aqueous solution, place it in an ice bath, and magnetically Stir for 24h. Finally, it is filtered, washed with water, dried, and then subjected to a deionized water swelling-dehydration cycle to remove remaining impurities, and after drying, a nanocomposite material of ethylene glycol-lactic acid block copolymer and polyaniline is obtained. From the FTIR spectrum (Fig. 1) of polyaniline and PEG-lactic acid block copolymer composite material, it can be seen that 1575 and 1496cm-1 are the quinone structure and benzene structure absorption peaks of polyaniline, and 1728 and 1110cm ^{- 1} correspond to carbonyl and The stretching vibration peak of COC indicates that there is an ester group in the molecular chain. This demonstrates the incorporation of polyaniline into the block copolymer. The test results of various physical and chemical properties of the nanocomposite are shown in Table 1, wherein the degradation time test is to soak the dry gel in a phosphate buffer solution of pH 7.4 (0.2g/LKCl, 0.2g/LKH ₂ PO ₄ , 8g/L1 .15g/LNa ₂ HPO ₄ ), the weight loss was tested at regular intervals.

Embodiment 2: Synthesis of ethylene glycol-glycolide block copolymer gel and polypyrrole nanocomposite material:

(1) Synthesis of ethylene glycol-glycolide block copolymer:

Under nitrogen protection, take 20g PEG (number average molecular weight 400) and 22.8g glycolide (0.2mol, M144), and add 25mg of tin octoate into a 100ml three-neck round bottom flask. The reaction mixture was stirred in vacuum at 190°C for 5h, then lowered to 150°C, stirred for 4h, and finally cooled to room temperature. The ethylene glycol-glycolide block copolymer is obtained, and the product is dissolved in dichloroethane, precipitated with anhydrous ether, filtered, and dried to obtain a purified ethylene glycol-glycolide block copolymer. From the SEM photo of Figure 3B, it can be seen that the synthesized hydrogel membrane material exhibits a honeycomb shape, and these penetrating holes provide a composite space for the conductive polymer.

(2) Synthesis of ethylene glycol-glycolide block copolymer terminated by acrylic acid:

Take 33g of the above-mentioned copolymer and dissolve it in 267ml of dichloromethane, put it in a 500mL round-bottomed flask, cool it to 3°C in an ice bath, replace the reaction bottle with nitrogen three times to obtain an anhydrous and oxygen-free environment, and add 15mL of Triethylamine and 12.2 mL of acryloyl chloride were stirred at 3°C for 10 h, and then at room temperature for 10 h. Remove triethylamine hydrochloride by filtration, and then add excess dry diethyl ether to the filtrate to obtain an acrylic acid group-terminated ethylene glycol-glycolide block copolymer. It was dissolved in dichloromethane and purified once by hexane precipitation. Finally, it was dried under vacuum at 60°C for 18 hours.

From the FTIR spectrum of PEG and glycolide (Figure 2), it can be seen that the carbonyl absorption peak at 1756cm ^-1 and the COC stretching vibration peak at 1110cm ^-1 indicate that there are ester groups in the molecular chain, and PEG and glycolide undergo polycondensation reaction. Compared with PEG, the hydroxyl absorption peak near 3500cm ^-1 in the block copolymer disappeared, which indicated that acryloyl chloride had reacted with the terminal hydroxyl of the block copolymer. The molecular weight analysis of the block copolymer shows that the molecular weight of the copolymer is higher than that of the PEG prepolymer, which all indicate that the resulting product is a block copolymer of acrylic acid-terminated PEG and glycolide.

(3) Synthesis of cross-linked gel system: Take 100 mL of 18% aqueous solution of ethylene glycol-glycolide block copolymer, neutralize it to pH 6 with KOH, add 3 mL of ammonium persulfate solution (18%) and mix, Place in a glass Petri dish and place in an oven at 80°C for 3 hours to initiate cross-linking polymerization. Add excess ethanol to quickly dehydrate, and then go through two water swelling-ethanol dehydration cycles to remove impurities. Finally, it was dried under vacuum at 60°C for 18 hours.

(4) In situ polymerization of pyrrole

Cut 6 g of the above dry gel, soak it in 5 mmol/L pyrrole aqueous solution at room temperature for 50 minutes, adjust the pH to 6 with HCl, then place the swollen gel in 15 mmol/L ammonium persulfate aqueous solution, and stir magnetically at room temperature for 24 hours . Finally, it is filtered, washed with water, dried, and then subjected to a deionized water swelling-dehydration cycle to remove remaining impurities, and the nanocomposite material of ethylene glycol-glycolide block copolymer and polypyrrole is obtained after drying. The test results of its physical and chemical properties are shown in Table 1.

Embodiment 3: Synthesis of ethylene glycol-ε-caprolactone block copolymer gel and polyaniline nanocomposite material:

(1) Synthesis of ethylene glycol-ε-caprolactone block copolymer:

Under the protection of nitrogen, take 30g PEG (number average molecular weight 600) and 45.6g ε-caprolactone (0.4mol, M114), and add 48mg of tin octoate into a 100ml three-neck round bottom flask. The reaction mixture was stirred under vacuum at 210°C for 3h, then lowered to 170°C, continued to stir for 1.5h, and finally cooled to room temperature. To obtain ethylene glycol-ε-caprolactone block copolymer, dissolve the product in dichloroethane, precipitate with anhydrous ether, filter, and dry to obtain purified ethylene glycol-ε-caprolactone block copolymer . From the SEM photo of Figure 3C, it can be seen that the synthesized hydrogel membrane material exhibits a honeycomb shape, and these penetrating holes provide a composite space for the conductive polymer.

(2) Synthesis of ethylene glycol-ε-caprolactone block copolymer terminated by acrylic acid:

Take 36g of the above-mentioned copolymer and dissolve it in 264ml of dichloromethane, put it in a 500mL round bottom flask, cool it to 5°C in an ice bath, replace the reaction bottle with nitrogen three times to obtain an anhydrous and oxygen-free environment, and add 21mL of Triethylamine and 20.3 mL of acryloyl chloride (0.25 mol) were stirred at 5° C. for 18 h, and then at room temperature for 18 h. Triethylamine hydrochloride was removed by filtration, and then an excess of dry diethyl ether was added to the filtrate to obtain an acrylic acid group-terminated ethylene glycol-ε-caprolactone block copolymer. It was dissolved in dichloromethane and purified once by hexane precipitation. Finally, it was dried under vacuum at 70°C for 36 hours.

(3) Synthesis of cross-linked gel system: Take 100 mL of 25% aqueous solution of ethylene glycol-ε-caprolactone block copolymer, neutralize it with KOH to pH 7, add 5 mL of potassium persulfate solution (25%) Mixed, placed in a glass petri dish, placed in an oven at 70°C for 6 hours to initiate cross-linking polymerization, added excess ethanol for rapid dehydration, and then went through two water swelling-ethanol dehydration cycles to remove impurities. Finally, it was dried under vacuum at 70°C for 36 hours.

(4) In situ polymerization of aniline

Cut 8g of the above dry gel, soak it in 20mmol/L aniline aqueous solution at room temperature for 45min, adjust the pH to 7 with HCl, then place the swollen gel in a 50mmol/L ferric chloride aqueous solution, and place it in an ice bath under magnetic force. Stir for 12h. Finally, it is filtered, washed with water, dried, and then subjected to a deionized water swelling-dehydration cycle to remove remaining impurities, and the nanocomposite material of ethylene glycol-ε-caprolactone block copolymer and polyaniline is obtained after drying. The test results of its physical and chemical properties are shown in Table 1.

Embodiment 4: Synthesis of ethylene glycol-delta-valerolactone block copolymer gel and polypyrrole nanocomposite:

(1) Synthesis of ethylene glycol-delta-valerolactone block copolymer:

Under the protection of nitrogen, take 40g PEG (number average molecular weight 800) and 60g δ-valerolactone (0.6mol, M100), and add 75mg of tin octoate into a 150ml three-neck round bottom flask. The reaction mixture was stirred under vacuum at 205°C for 4h, then lowered to 165°C, continued to stir for 2h, and finally cooled to room temperature. To obtain ethylene glycol-δ-valerolactone block copolymer, dissolve the product in ethylene dichloride, precipitate with anhydrous ether, filter, and dry to obtain purified ethylene glycol-δ-valerolactone block copolymer . It can be seen from the SEM photo of Figure 3D that the synthesized hydrogel membrane material exhibits a honeycomb shape, and these penetrating holes provide a composite space for the conductive polymer.

(2) Synthesis of ethylene glycol-delta-valerolactone block copolymer terminated by acrylic acid:

Take 39g of the above-mentioned copolymer and dissolve it in 261ml of dichloromethane, put it in a 500mL round bottom flask, cool it to 0°C in an ice bath, replace the reaction bottle with nitrogen three times to obtain an anhydrous and oxygen-free environment, and add 23.4 mL of triethylamine and 18.7 mL of acryloyl chloride (0.23 mol) were stirred at 0° C. for 14 h, and then at room temperature for 14 h. Remove triethylamine hydrochloride by filtration, and then add excess dry diethyl ether to the filtrate to obtain an acrylic acid group-terminated ethylene glycol-δ-valerolactone block copolymer. It was dissolved in dichloromethane and purified once by hexane precipitation. Finally, it was dried under vacuum at 70°C for 26 hours.

(3) Synthesis of cross-linked gel system: Take 100ml of 25% aqueous solution of the above-mentioned block copolymer, add 0.2ml of 0.3g/mL 2,2-dimethyl-2-diphenylacetophenone N-ethylene base pyrrolidone solution. As for a glass Petri dish, cross-linking was initiated by irradiation with an argon ion UV laser lamp for 60 s. Add excess ethanol to quickly dehydrate, and then go through two water swelling-ethanol dehydration cycles to remove impurities. Placed at 70°C for 16 hours in vacuum.

(4) In situ polymerization of pyrrole

Cut 8g of the above dry gel, soak it in 30mmol/L pyrrole aqueous solution at room temperature for 40min, adjust the pH to 6.5 with HCl, then place the swollen gel in 45mmol/L ferric chloride aqueous solution, and stir magnetically at room temperature 14h. Finally, it is filtered, washed with water, dried, and then subjected to a deionized water swelling-dehydration cycle to remove remaining impurities, and after drying, a nanocomposite material of ethylene glycol-δ-valerolactone block copolymer and polypyrrole is obtained. The test results of its physical and chemical properties are shown in Table 1.

Embodiment 5: Synthesis of ethylene glycol-γ-butyrolactone block copolymer gel and polyaniline nanocomposite material:

(1) Synthesis of ethylene glycol-γ-butyrolactone block copolymer:

Under nitrogen protection, take 50g PEG (number average molecular weight 1000) and 68.8g gamma-butyrolactone (0.8mol, M86), and add 60mg of tin octoate into a 100ml three-neck round bottom flask. The reaction mixture was stirred under vacuum at 200°C for 4h, then lowered to 160°C, stirred for 2h, and finally cooled to room temperature. Obtain ethylene glycol-γ-butyrolactone block copolymer, dissolve the product in ethylene dichloride, precipitate with anhydrous ether, filter, and dry to obtain purified ethylene glycol-γ-butyrolactone block copolymer . From the SEM photo of Figure 3E, it can be seen that the synthesized hydrogel membrane material exhibits a honeycomb shape, and these penetrating holes provide a composite space for the conductive polymer.

(2) Synthesis of ethylene glycol-γ-butyrolactone block copolymer terminated by acrylic acid:

Take 42g of the above-mentioned copolymer and dissolve it in 258ml of dichloromethane, put it in a 500mL round bottom flask, cool it to 4°C in an ice bath, replace the reaction bottle with nitrogen three times to obtain an anhydrous and oxygen-free environment, and add 27.8 mL of triethylamine and 14.6 mL of acryloyl chloride (0.18 mol) were stirred at 0° C. for 16 h, and then at room temperature for 16 h. The triethylamine hydrochloride was removed by filtration, and then an excess of dry diethyl ether was added to the filtrate to obtain an acrylic acid group-terminated ethylene glycol-γ-butyrolactone block copolymer. It was dissolved in dichloromethane and purified once by hexane precipitation. Finally, it was dried under vacuum at 75°C for 24 hours.

(3) Synthesis of cross-linked gel system: Take 100ml of the 18% aqueous solution of the above-mentioned block copolymer, add 0.4ml of 0.3g/mL 2,2-dimethyl-2-diphenylacetophenone N-ethylene base pyrrolidone solution. As for a glass Petri dish, cross-linking was initiated by irradiation with an argon-ion UV laser for 40 s. Add excess ethanol to quickly dehydrate, and then go through two cycles of water swelling-ethanol dehydration to remove impurities, and then vacuum-dry at 65°C for 20h.

(4) In situ polymerization of pyrrole

Cut 10g of the above dry gel, soak it in 50mmol/L pyrrole aqueous solution at room temperature for 60min, adjust the pH to 7 with HCl, then place the swollen gel in 50mmol/L ammonium persulfate aqueous solution, and stir magnetically at room temperature for 16h . Finally, it is filtered, washed with water, dried, and then subjected to a deionized water swelling-dehydration cycle to remove remaining impurities, and after drying, a nanocomposite material of ethylene glycol-γ-butyrolactone block copolymer and polypyrrole is obtained. The test results of its physical and chemical properties are shown in Table 1.

Table 1 Physical and chemical performance test results

Example PEG molecular weight Hydroxy acid Molecular weight of block copolymer Appearance of gel after crosslinking Gel water absorption times Water absorption times of normal saline Composite complete degradation time (days) 1 200 Lactic acid 900 transparent 380 80 45 2 400 glycolide 1080 transparent 250 60 10 3 600 ε-caprolactone 1120 translucent 500 135 20 4 800 δ-valerolactone 1500 transparent 320 70 30 5 1000 γ-butyrolactone 1680 translucent 460 100 8

Claims (10)

1. Bioactive hydrogel-conductive polymer nanocomposite material, characterized in that it is a composite material of ethylene glycol-hydroxy acid block copolymer and polypyrrole or polyaniline, by mass percentage, conductive polymer polypyrrole or Polyaniline accounts for 7% to 50% of the total mass of the composite material. 2. The bioactive hydrogel-conducting polymer nanocomposite material according to claim 1, wherein the hydroxy acid is lactic acid, glycolide, butyrolactone, valerolactone or caprolactone. 3. the synthetic method of bioactive hydrogel-conductive polymer nanocomposite material as claimed in claim 1, is characterized in that comprising the following steps: 1) Synthesis of ethylene glycol-hydroxy acid block copolymer Under the protection of nitrogen, polyethylene glycol is mixed with hydroxyacid, the molar ratio of hydroxyacid to PEG is 2-10, according to mass percentage, then add 0.05%-0.1% tin octoate catalyst of the total system, vacuumize, and heat up to Stir at 190-210°C, lower to 150-170°C to continue stirring reaction, cool to room temperature to obtain ethylene glycol-hydroxy acid block copolymer, dissolve the product in dichloroethane, precipitate with anhydrous ether, filter, and dry , to obtain purified ethylene glycol-hydroxy acid block copolymer; 2) Synthesis of acrylic acid-terminated ethylene glycol-hydroxy acid block copolymers Take the above-mentioned purified ethylene glycol-hydroxy acid block copolymer and dissolve it in dichloromethane, the concentration is 10%～14% by mass percentage, cool to 0～5°C in an ice bath, molar ratio, in anhydrous Add acryloyl chloride with a concentration of 0.5-0.83 mol and triethylamine with a concentration of 0.33-0.67 mol under anaerobic conditions, stir and react at 0-5°C for 10-18 hours, then stir and react at room temperature for 12-18 hours, and filter out Triethylamine hydrochloride, add excess dry diethyl ether to the filtrate to obtain acrylic acid group-terminated ethylene glycol-hydroxy acid block copolymer, acrylic acid group-terminated ethylene glycol-hydroxy acid block copolymer The product was dissolved in dichloromethane, purified by hexane precipitation, and dried; 3) Synthesis of cross-linked gel dissolving the ethylene glycol-hydroxy acid block copolymer terminated by the acrylic acid group in water, and obtaining a gel by photo-initiated cross-linking or free radical cross-linking; 4) In-situ polymerization of pyrrole or aniline monomer The gel obtained in step 3) is dried, soaked in pyrrole or aniline hydrochloric acid aqueous solution with a pH of 3 to 7 and a monomer concentration of 5 to 50 mmol/L to swell, and then the gel swollen by the monomer solution is placed In the initiator solution, stirred in ice bath to room temperature, the monomer polymerizes in the gel cross-linked network system to form an interpenetrating network system, which is filtered, washed with water, dried, and then subjected to water swelling-ethanol dehydration cycle to remove impurities. After drying, a nanocomposite material of ethylene glycol-hydroxy acid block copolymer and polypyrrole or polyaniline is obtained. 4. The method for synthesizing bioactive hydrogel-conductive polymer nanocomposites according to claim 3, characterized in that the polyethylene glycol has a molecular weight of 200-1000. 5. the synthetic method of tool bioactive hydrogel-conductive polymer nanocomposite as claimed in claim 3, is characterized in that in step 3) in, described initiator is ammonium persulfate, potassium persulfate or persulfate Ammonium sulfate - 18% to 25% aqueous solution of sodium sulfite. 6. The synthetic method of bioactive hydrogel-conductive polymer nanocomposite material as claimed in claim 5, characterized in that the mol ratio of ammonium persulfate and sodium sulfite is 1:1. 7. the synthetic method of tool bioactive hydrogel-conductive polymer nanocomposite as claimed in claim 3, it is characterized in that described photoinitiated crosslinking is to get the ethylene glycol-hydroxy acid of above-mentioned acrylic acid group termination The block copolymer is made into the aqueous solution A of the ethylene glycol-hydroxy acid block copolymer end-capped by the acrylic acid group of 18%～25% by mass percent concentration, and the photoinitiator 2,2-dimethyl-2- Diphenylacetophenone was dissolved in N-vinylpyrrolidone to form 0.3g/mL solution B, solution A and solution B were mixed at a volume ratio of 1000:2-5, and cross-linking was initiated by light irradiation for 20-60s, Add excess ethanol for dehydration, then undergo water swelling-ethanol dehydration cycle to remove impurities, and finally dry; 8. the synthetic method of tool bioactive hydrogel-conductive polymer nanocomposite as claimed in claim 3, it is characterized in that described free radical cross-linking is to get the ethylene glycol-hydroxy acid intercalation of acrylic acid group termination The segment copolymer is made into an aqueous solution of ethylene glycol-hydroxy acid block copolymer terminated by acrylic acid groups with a concentration of 18% to 25% by mass percentage, neutralized with KOH to a pH of 6 to 7, adding an initiator solution and mixing, After mixing, the mass percentage of the copolymer and the initiator is 100:1~5, put it in an oven at 70~90°C to initiate cross-linking polymerization, add excess ethanol to dehydrate quickly, and then go through a water swelling-ethanol dehydration cycle to remove impurities. final drying; 9. The method for synthesizing bioactive hydrogel-conducting polymer nanocomposites according to claim 3, characterized in that in step 4), the initiator is ammonium persulfate or ferric chloride. 10. The method for synthesizing bioactive hydrogel-conducting polymer nanocomposites as claimed in claim 3, characterized in that the molar ratio of initiator concentration:monomer concentration=1˜3:1.

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