Preparation method of medical polycarbonate with high biocompatibility

Abstract

The invention discloses a preparation method of medical polycarbonate with high biocompatibility, and belongs to the technical field of polycarbonate preparation. The preparation method of the medical polycarbonate with high biocompatibility comprises the following steps: step 1, adding bisphenol A into dichloromethane, introducing phosgene, adding triethylamine, and continuously stirring and reacting at low temperature to obtain a prepolymer; step 2, adding modified polycaprolactone into dichloromethane, slowly adding into the prepolymer, and continuously stirring to react, so as to obtain a modified prepolymer; and 3, adding an auxiliary agent into deionized water, stirring, adding into the modified prepolymer, adding triethylamine, continuously reacting, adding ethanol, washing, drying, dissolving, precipitating, filtering and drying to obtain the medical polycarbonate with high biocompatibility. The polycarbonate prepared by the method has excellent biocompatibility, mechanical property and hydrophilic property.

Description

Technical Field

[0001] The present invention belongs to the technical field of the preparation of medical polycarbonate, and particularly relates to a preparation method of a medical polycarbonate with high biocompatibility. Background Art

[0002] As a thermoplastic engineering plastic with excellent physical properties and biocompatibility, polycarbonate has gradually occupied an important position in the medical field since China began to research and develop medical plastic products in the 1970s. In recent years, the global medical PC market scale has continued to expand, and it is expected to reach 290 million US dollars by 2029, with a compound annual growth rate of 9.7%, showing its huge market potential and broad application prospects.

[0003] Polycarbonate is favored by the medical field due to its unique material properties. It has good transparency, impact resistance, heat resistance, chemical resistance, and excellent mechanical strength, which enable it to be competent for a variety of medical application scenarios. More importantly, medical-grade polycarbonate has passed biocompatibility tests such as ISO 10993 and can be compatible with sensitive parts of the human body such as blood and tissues, and is particularly suitable for the manufacture of implantable medical devices. In addition, polycarbonate is easy to process and form, and complex medical device components can be manufactured by various methods such as injection molding and extrusion, further enhancing its applicability in the medical field. Summary of the Invention

[0004] The purpose of the present invention is to provide a preparation method of a medical polycarbonate with high biocompatibility, aiming to solve the technical problems of poor biocompatibility, mechanical properties, and hydrophilic properties of polycarbonate in the prior art.

[0005] In order to achieve the above purpose, the present invention adopts the following technical solutions: The present invention provides a preparation method of a medical polycarbonate with high biocompatibility, comprising the following steps: Step 1: Add bisphenol A to dichloromethane, stir, and then introduce phosgene under a low-temperature environment. After the introduction is completed, add triethylamine and continuously stir and react at low temperature to obtain a prepolymer; Step 2: Add modified polycaprolactone to dichloromethane, stir, and then slowly add it to the prepolymer and continue to stir and react. After the reaction ends, a modified prepolymer is obtained; Step 3: Add an auxiliary agent to deionized water, stir, then add it to the modified prepolymer, perform emulsification treatment, add triethylamine, continue to react. After the reaction ends, add ethanol, wash, dry, dissolve, precipitate, filter, and dry to obtain a medical polycarbonate with high biocompatibility.

[0006] Preferably, in the first step, the dosage ratio of bisphenol A, dichloromethane, phosgene and triethylamine is (10 - 13) g : (100 - 120) mL : (5.2 - 6.5) g : (1 - 1.8) mL, the low-temperature environment temperature is 0 - 5 °C, the feeding time is 1 - 2 h, and the stirring reaction time is 2 - 4 h.

[0007] Preferably, the preparation method of the modified polycaprolactone includes the following steps: Q1: Add lactobionic acid into a container containing a mixed solution of tetramethylethylenediamine and hydrochloric acid, stir to dissolve, then add N-hydroxysuccinimide and EDC hydrochloride, stir and react in a water bath in the dark. Subsequently, add polylysine and continue to stir and react in the dark. After the reaction is completed, dialyze and freeze-dry to obtain product 1; Q2: Add calcium hydride to Ɛ-caprolactone, mix well and let stand, then rotary evaporate and distill under reduced pressure to obtain dehydrated Ɛ-caprolactone; Add hydroxyl-terminated polybutadiene, dehydrated Ɛ-caprolactone and stannous octoate into a container filled with argon, stir and react in an oil bath. After the reaction is completed, cool, dissolve the product, precipitate, wash and dry to obtain product 2; Q3: Add product 1, product 2 and lactide into a container containing dichloromethane, evacuate, then add 1,8-diazabicyclo[5.4.0]undec-7-ene, stir and react at room temperature. After the reaction is completed, add benzoic acid, precipitate, wash and dry under vacuum to obtain the modified polycaprolactone.

[0008] In the above process, first, lactobionic acid reacts with EDC hydrochloride to form an unstable O-acylisourea intermediate. Subsequently, N-hydroxysuccinimide attacks the O-acylisourea intermediate to form a more stable ester. Then, the primary amine of polylysine nucleophilically attacks the carbonyl carbon of the ester to form an amide bond, obtaining product 1; Stannous octoate coordinates with the hydroxyl group at the end of hydroxyl-terminated polybutadiene to activate the oxygen atom of the hydroxyl group, then attacks the carbonyl carbon of dehydrated Ɛ-caprolactone to open the ring and form an ester bond. Then, stannous octoate catalyzes chain growth through a coordination-insertion mechanism to form product 2; 1,8-diazabicyclo[5.4.0]undec-7-ene, as a strong base, reacts with product 1 and product 2 to obtain an alkoxide anion. The alkoxide anion nucleophilically attacks the carbonyl carbon of lactide to open the ring and form an ester bond. Then, add benzoic acid to terminate the reaction to obtain the modified polycaprolactone.

[0009] Preferably, in Q1, the dosage ratio of lactic acid, tetramethylethylenediamine, hydrochloric acid, N-hydroxysuccinimide, EDC hydrochloride and polylysine is (0.92-1.08) g: (8-12) mL: (10-18) mL: (0.056-0.063) g: (0.22-0.28) g: (0.42-0.48) g. The reaction temperature of water bath stirring in the dark is 30-35 °C, the reaction time is 30-45 min, the continuous stirring reaction time in the dark is 30-42 h, the dialysis time is 70-85 h, and the freeze-drying time is 42-50 h.

[0010] Preferably, in Q2, the dosage ratio of hydroxyl-terminated polybutadiene, Ɛ-caprolactone after water removal and stannous octoate is (5-7) g: (8-12) g: (0.2-0.25) g. The reaction temperature of oil bath stirring is 110-130 °C, the reaction time is 20-24 h, the product is dissolved in dichloromethane, and methanol is added for precipitation; in Q3, the dosage ratio of product 1, product 2, lactide, dichloromethane and 1,8-diazabicyclo[5.4.0]undec-7-ene is (5-8.7) g: (11-18.5) g: (2-3.5) g: (10-15) mL: (0.52-0.85) mL, and the reaction time of stirring at room temperature is 8-12 h.

[0011] Preferably, in the second step, the dosage ratio of modified polycaprolactone, dichloromethane and prepolymer is (2-5) g: (50-75) mL: (22-28) mL, the continuous stirring reaction time is 1-2 h, and the stirring temperature is 10-20 °C.

[0012] Preferably, the preparation method of the auxiliary agent includes the following steps: S1: Add glutamic acid, deionized water, potassium carbonate and ether into a container, stir vigorously in an ice bath environment, and then use a constant pressure dropping funnel to drop the mixed solution of acryloyl chloride and ether into the container, stir and react at room temperature. After the reaction, add sodium hydroxide solution to adjust the pH, extract, dry, rotary evaporate, concentrate, and dry to obtain a white powder; S2: Add phenylalanine, sodium hydroxide and deionized water into a container, stir vigorously in an ice bath environment, then slowly drop acryloyl chloride, continue to stir and react at low temperature. After the reaction, acidify, precipitate, filter by suction, wash, and dry in vacuum to obtain a light yellow powder; S3: Add the white powder and the light yellow powder into deionized water, then add sodium hydroxide, then add ammonium persulfate and methylene bisacrylamide, stir and dissolve, add to a mold, and heat and react to obtain the auxiliary agent.

[0013] In the above process, the synthesis reaction formula of the auxiliary agent is as follows:

[0014] The results of mass spectrometry analysis of the white powder are: m / z: 201.06 (100.0%), 202.07 (9.0%), 203.07 (1.4%); the results of mass spectrometry analysis of the light yellow powder are: m / z: 219.09 (100.0%), 220.09 (13.5%).

[0015] Preferably, in the step S1, the dosage ratio of glutamic acid, deionized water, potassium carbonate and acryloyl chloride is (7 - 8) g : (60 - 100) mL : (12 - 18) g : (8 - 10) mL, the stirring reaction time at room temperature is 3 - 4 h, the concentration of the sodium hydroxide solution is 2 mol / L, the pH is adjusted to 12, and extraction is carried out with ethyl acetate and drying is carried out with anhydrous sodium sulfate.

[0016] Preferably, in the step S2, the dosage ratio of phenylalanine, sodium hydroxide, deionized water and acryloyl chloride is (6 - 8) g : (3 - 4.3) g : (30 - 50) mL : (3 - 4.2) mL, the stirring reaction time at low temperature is 3 - 4 h, and acidification is carried out by adding 6 mol / L hydrochloric acid; in the step S3, the dosage ratio of the white powder, the light yellow powder, deionized water, sodium hydroxide, ammonium persulfate and methylene bisacrylamide is (2 - 5) g : (2 - 4.3) g : (10 - 15) mL : (1.3 - 1.8) g : (0.02 - 0.04) g : (0.003 - 0.006) g, the heating reaction temperature is 60 - 70 °C, and the time is 3 - 5 h.

[0017] Preferably, in the third step, the dosage ratio of the auxiliary agent, deionized water, modified prepolymer and triethylamine is (1 - 3) g : (30 - 50) mL : (18 - 25) g : (0.5 - 1) mL, emulsification treatment is carried out using a high - speed homogenizer for 10 - 15 min, and the continuous reaction time is 1 - 2 h.

[0018] In summary, due to the adoption of the above - mentioned technical solutions, the beneficial effects of the present invention are as follows: 1. First, using lactobionic acid, N - hydroxysuccinimide, EDC hydrochloride, Ɛ - caprolactone, hydroxyl - terminated polybutadiene and 1,8 - diazabicyclo[5.4.0]undec - 7 - ene as the main raw materials, a modified polycaprolactone is prepared. Subsequently, using glutamic acid, acryloyl chloride, phenylalanine and ammonium persulfate as the main raw materials, an auxiliary agent is prepared. During the preparation process of the medical polycarbonate, adding the modified polycaprolactone and the auxiliary agent can effectively improve its biocompatibility, mechanical properties and hydrophilic properties.

[0019] 2. The modified polycaprolactone prepared in the present invention is added to the preparation process of medical polycarbonate, which can effectively improve the biocompatibility and mechanical properties of the material. The addition of lactobionic acid and polylysine endows the modified polycaprolactone with positive surface charge and hydrophilicity, promoting cell adhesion and proliferation. The hydroxyl group of lactobionic acid can also interact with the glycoprotein on the cell membrane surface through hydrogen bonds, enhancing biocompatibility. At the same time, the segment formed by the ring-opening of lactide has excellent biodegradability and tissue compatibility; the flexible segment of the used hydroxyl-terminated polybutadiene can form a microphase separation structure with the crystalline segment of polycaprolactone, absorbing impact energy and improving the toughness of the material.

[0020] 3. The additive prepared in the present invention is added to the preparation process of medical polycarbonate, which can effectively improve the hydrophilicity, mechanical properties and promote biodegradation of the material. The free carboxylic acid groups contained in the additive can improve the hydrophilicity of polycarbonate, reduce the contact angle and promote liquid wetting. At the same time, the three-dimensional cross-linked network structure contained in the additive restricts the slippage of molecular chains, improving the tensile strength of the material. The benzene ring structure contained in phenylalanine increases the rigidity of the segment, reducing the deformation of polycarbonate under stress and enhancing the mechanical properties. The ester bonds and amide bonds contained in the additive can undergo hydrolysis, releasing amino acid degradation products and promoting tissue repair. Detailed implementation mode

[0021] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of them. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts belong to the scope of protection of the present invention.

[0022] Example 1: This example discloses a preparation method of modified polycaprolactone, which includes the following steps: Q1: Add 1 g of lactobionic acid to a container containing a mixed solution of 10 mL of tetramethylethylenediamine and 14 mL of hydrochloric acid. After stirring and dissolving, add 0.06 g of N-hydroxysuccinimide and 0.25 g of EDC hydrochloride. Stir and react at 30 °C in the dark for 45 min, then add 0.45 g of polylysine, and continue to stir and react in the dark for 36 h. After the reaction, dialyze for 72 h and freeze-dry for 48 h to obtain Product 1; Q2: Add calcium hydride to ε-caprolactone, mix well and let stand, then rotary evaporate and distill under reduced pressure to obtain dehydrated ε-caprolactone; Add 6 g of hydroxyl-terminated polybutadiene, 10 g of dehydrated ε-caprolactone and 0.23 g of stannous octoate to a container filled with argon. Stir and react at 110 °C in an oil bath for 24 h. After the reaction, cool, dissolve the product with dichloromethane, add methanol for precipitation, wash and dry to obtain Product 2; Q3: 6.6 g of Product 1, 14.3 g of Product 2 and 2.75 g of lactide were added to a container containing 12.5 mL of dichloromethane. The container was evacuated, and then 0.68 mL of 1,8-diazabicyclo[5.4.0]undec-7-ene was added. The reaction was stirred at room temperature for 12 h. After the reaction was completed, benzoic acid was added, and the mixture was precipitated, washed, and dried under vacuum to obtain modified polycaprolactone.

[0023] This example discloses a preparation method of an auxiliary agent, which includes the following steps: S1: 7.5 g of glutamic acid, 80 mL of deionized water, 15 g of potassium carbonate and 30 mL of diethyl ether were added to a container. The mixture was vigorously stirred in an ice bath environment, and then a mixed solution of 9 mL of acryloyl chloride and 20 mL of diethyl ether was added dropwise to the container using a constant pressure dropping funnel. The reaction was stirred at room temperature for 3 h. After the reaction was completed, a 2 mol / L sodium hydroxide solution was added to adjust the pH to 12. The mixture was extracted with ethyl acetate, dried with anhydrous sodium sulfate, rotary evaporated, concentrated, and dried to obtain a white powder. S2: 7 g of phenylalanine, 3.6 g of sodium hydroxide and 40 mL of deionized water were added to a container. The mixture was vigorously stirred in an ice bath environment, and then 3.6 mL of acryloyl chloride was slowly added dropwise. The reaction was continued to be stirred at low temperature for 4 h. After the reaction was completed, 6 mol / L hydrochloric acid was added for acidification, and the mixture was precipitated, filtered by suction, washed, and dried under vacuum to obtain a pale yellow powder. S3: 3.5 g of the white powder and 3.1 g of the pale yellow powder were added to 12.5 mL of deionized water, and then 1.5 g of sodium hydroxide was added. Subsequently, 0.03 g of ammonium persulfate and 0.004 g of methylene bisacrylamide were added. The mixture was stirred and dissolved, and then added to a mold. The reaction was heated at 65 °C for 5 h to obtain the auxiliary agent.

[0024] This example discloses a preparation method of a highly biocompatible medical polycarbonate, which includes the following steps: Step 1: 11.5 g of bisphenol A was added to 110 mL of dichloromethane and stirred. Then, 5.6 g of phosgene was introduced into the mixture at a low temperature of 2 °C for 2 h. After the introduction was completed, 1.4 mL of triethylamine was added, and the reaction was continuously stirred at low temperature for 4 h to obtain a prepolymer. Step 2: 3.5 g of modified polycaprolactone was added to 62.5 mL of dichloromethane and stirred. Then, it was slowly added to 25 mL of the prepolymer, and the reaction was continued to be stirred at 15 °C for 2 h. After the reaction was completed, a modified prepolymer was obtained. Step 3: 2 g of the auxiliary agent was added to 40 mL of deionized water. After stirring, it was added to 21 g of the modified prepolymer. The mixture was emulsified using a high-speed homogenizer for 15 min, and then 0.75 mL of triethylamine was added. The reaction was continued for 2 h. After the reaction was completed, ethanol was added, and the mixture was washed, dried, dissolved, precipitated, filtered, and dried to obtain a highly biocompatible medical polycarbonate.

[0025] Example 2: This example discloses a preparation method of modified polycaprolactone, which includes the following steps: Q1: Add 0.92 g of lactobionic acid into a container containing 8 mL of a mixed solution of tetramethylethylenediamine and 10 mL of hydrochloric acid. After stirring and dissolving, add 0.056 g of N-hydroxysuccinimide and 0.22 g of EDC hydrochloride. Stir and react in the dark in a water bath at 30 °C for 45 min. Then add 0.42 g of polylysine and continue to stir and react in the dark for 36 h. After the reaction is completed, dialyze for 72 h and freeze-dry for 48 h to obtain Product 1; Q2: Add calcium hydride to ε-caprolactone, mix well and let stand, then rotary evaporate and distill under reduced pressure to obtain dehydrated ε-caprolactone. Add 5 g of hydroxyl-terminated polybutadiene, 8 g of dehydrated ε-caprolactone and 0.2 g of stannous octoate into a container filled with argon. Stir and react in an oil bath at 110 °C for 24 h. After the reaction is completed, cool, dissolve the product with dichloromethane, add methanol for precipitation, wash and dry to obtain Product 2; Q3: Add 5 g of Product 1, 11 g of Product 2 and 2 g of lactide into a container containing 10 mL of dichloromethane, evacuate, then add 0.52 mL of 1,8-diazabicyclo[5.4.0]undec-7-ene, stir and react at room temperature for 12 h. After the reaction is completed, add benzoic acid, precipitate, wash and dry under vacuum to obtain modified polycaprolactone.

[0026] This example discloses a preparation method of an additive, which includes the following steps: S1: Add 7 g of glutamic acid, 60 mL of deionized water, 12 g of potassium carbonate and 30 mL of diethyl ether into a container. Stir vigorously in an ice bath environment, then use a constant pressure dropping funnel to drop a mixed solution of 8 mL of acryloyl chloride and 20 mL of diethyl ether into the container. Stir and react at room temperature for 3 h. After the reaction is completed, add 2 mol / L sodium hydroxide solution to adjust the pH to 12, extract with ethyl acetate, dry with anhydrous sodium sulfate, rotary evaporate, concentrate and dry to obtain a white powder; S2: Add 6 g of phenylalanine, 3 g of sodium hydroxide and 30 mL of deionized water into a container. Stir vigorously in an ice bath environment, then slowly drop 3 mL of acryloyl chloride, continue to stir and react at low temperature for 4 h. After the reaction is completed, acidify with 6 mol / L hydrochloric acid, precipitate, filter by suction, wash and dry under vacuum to obtain a light yellow powder; S3: Add 2 g of the white powder and 2 g of the light yellow powder into 10 mL of deionized water, then add 1.3 g of sodium hydroxide, then add 0.02 g of ammonium persulfate and 0.003 g of methylenebisacrylamide, stir and dissolve, add to a mold, and heat and react at 65 °C for 5 h to obtain the additive.

[0027] This embodiment discloses a preparation method of a medical polycarbonate with high biocompatibility, including the following steps: Step 1: Add 10 g of bisphenol A to 100 mL of dichloromethane, stir, and then introduce 5.2 g of phosgene at a low temperature of 2 °C for 2 h. After the introduction is completed, add 1 mL of triethylamine and continuously stir the reaction at a low temperature for 4 h to obtain a prepolymer. Step 2: Add 2 g of modified polycaprolactone to 50 mL of dichloromethane, stir, and then slowly add it to 22 mL of the prepolymer, and continue to stir the reaction at 15 °C for 2 h. After the reaction is completed, a modified prepolymer is obtained. Step 3: Add 1 g of an auxiliary agent to 30 mL of deionized water, stir, and then add it to 18 g of the modified prepolymer. After emulsification treatment with a high-speed homogenizer for 15 min, add 0.5 mL of triethylamine and continue the reaction for 2 h. After the reaction is completed, add ethanol, wash, dry, dissolve, precipitate, filter, and dry to obtain a medical polycarbonate with high biocompatibility.

[0028] Example 3: This embodiment discloses a preparation method of modified polycaprolactone, including the following steps: Q1: Add 1.08 g of lactobionic acid to a container containing a mixed solution of 12 mL of tetramethylethylenediamine and 18 mL of hydrochloric acid. After stirring and dissolving, add 0.063 g of N-hydroxysuccinimide and 0.48 g of EDC hydrochloride, and stir the reaction in the dark at 30 °C for 45 min. Subsequently, add 0.45 g of polylysine and continue to stir the reaction in the dark for 36 h. After the reaction is completed, dialyze for 72 h and freeze-dry for 48 h to obtain Product 1. Q2: Add calcium hydride to ε-caprolactone, mix well and let it stand, then rotary evaporate and distill under reduced pressure to obtain dehydrated ε-caprolactone; add 7 g of hydroxyl-terminated polybutadiene, 12 g of dehydrated ε-caprolactone, and 0.25 g of stannous octoate to a container filled with argon, and stir the reaction in an oil bath at 110 °C for 24 h. After the reaction is completed, cool, dissolve the product with dichloromethane, add methanol for precipitation, wash, and dry to obtain Product 2. Q3: Add 8.7 g of Product 1, 18.5 g of Product 2, and 3.5 g of lactide to a container containing 15 mL of dichloromethane, evacuate, and then add 0.85 mL of 1,8-diazabicyclo[5.4.0]undec-7-ene, and stir the reaction at room temperature for 12 h. After the reaction is completed, add benzoic acid, precipitate, wash, and dry under vacuum to obtain modified polycaprolactone.

[0029] This embodiment discloses a preparation method of an auxiliary agent, including the following steps: S1: Add 8 g of glutamic acid, 100 mL of deionized water, 18 g of potassium carbonate, and 30 mL of diethyl ether into a container, stir vigorously in an ice bath environment, and then use a constant pressure dropping funnel to drop a mixed solution of 10 mL of acryloyl chloride and 20 mL of diethyl ether into the container. Stir and react at room temperature for 3 h. After the reaction, add 2 mol / L sodium hydroxide solution to adjust the pH to 12, extract with ethyl acetate, dry with anhydrous sodium sulfate, rotary evaporate, concentrate, and dry to obtain a white powder; S2: Add 8 g of phenylalanine, 4.3 g of sodium hydroxide, and 50 mL of deionized water into a container, stir vigorously in an ice bath environment, then slowly drop 4.2 mL of acryloyl chloride, and continue to stir and react at low temperature for 4 h. After the reaction, add 6 mol / L hydrochloric acid for acidification, precipitate, filter, wash, and vacuum dry to obtain a light yellow powder; S3: Add 5 g of the white powder and 4.3 g of the light yellow powder into 15 mL of deionized water, then add 1.8 g of sodium hydroxide, and then add 0.04 g of ammonium persulfate and 0.006 g of methylene bisacrylamide, stir and dissolve, add to a mold, and heat and react at 65 °C for 5 h to obtain an additive.

[0030] This example discloses a preparation method of a highly biocompatible medical polycarbonate, including the following steps: Step 1: Add 13 g of bisphenol A into 120 mL of dichloromethane, stir, and then introduce 6.5 g of phosgene in a low-temperature environment of 2 °C for 2 h. After the introduction, add 1.8 mL of triethylamine, and continuously stir and react at low temperature for 4 h to obtain a prepolymer; Step 2: Add 5 g of modified polycaprolactone into 75 mL of dichloromethane, stir, and then slowly add it to 28 mL of the prepolymer, and continue to stir and react at 15 °C for 2 h. After the reaction, obtain a modified prepolymer; Step 3: Add 3 g of the additive into 50 mL of deionized water, stir, and then add it to 25 g of the modified prepolymer. After emulsification treatment with a high-speed homogenizer for 15 min, add 1 mL of triethylamine, and continue to react for 2 h. After the reaction, add ethanol, wash, dry, dissolve, precipitate, filter, and dry to obtain a highly biocompatible medical polycarbonate.

[0031] Example 4: This example discloses a preparation method of modified polycaprolactone, including the following steps: Q1: Add 0.96 g of lactobionic acid into a container containing a mixed solution of 9 mL of tetramethylethylenediamine and 12 mL of hydrochloric acid, stir and dissolve, add 0.058 g of N-hydroxysuccinimide and 0.24 g of EDC hydrochloride, stir and react in a 30 °C water bath in the dark for 45 min, then add 0.43 g of polylysine, and continue to stir and react in the dark for 36 h. After the reaction, dialyze for 72 h and freeze-dry for 48 h to obtain Product 1; Q2: Calcium hydride was added to ε-caprolactone. After mixing evenly, it was left standing, then rotary evaporated and distilled under reduced pressure to obtain ε-caprolactone after water removal; 5.5 g of hydroxyl-terminated polybutadiene, 9 g of ε-caprolactone after water removal and 0.21 g of stannous octoate were added to a container filled with argon, and stirred and reacted in an oil bath at 110 °C for 24 h. After the reaction was completed, it was cooled, the product was dissolved with dichloromethane, methanol was added for precipitation, washed and dried to obtain product 2; Q3: 5.7 g of product 1, 12.1 g of product 2 and 2.2 g of lactide were added to a container containing 11 mL of dichloromethane, evacuated, then 0.58 mL of 1,8-diazabicyclo[5.4.0]undec-7-ene was added, and stirred and reacted at room temperature for 12 h. After the reaction was completed, benzoic acid was added for precipitation, washed and dried under vacuum to obtain modified polycaprolactone.

[0032] This example discloses a preparation method of an additive, including the following steps: S1: 7.2 g of glutamic acid, 90 mL of deionized water, 13 g of potassium carbonate and 30 mL of diethyl ether were added to a container, and stirred vigorously in an ice bath environment. Then, a mixed solution of 8.5 mL of acryloyl chloride and 20 mL of diethyl ether was added dropwise to the container using a constant pressure dropping funnel, and stirred and reacted at room temperature for 3 h. After the reaction was completed, 2 mol / L sodium hydroxide solution was added to adjust the pH to 12, extracted with ethyl acetate, dried with anhydrous sodium sulfate, rotary evaporated, concentrated and dried to obtain a white powder; S2: 6.5 g of phenylalanine, 3.4 g of sodium hydroxide and 35 mL of deionized water were added to a container, and stirred vigorously in an ice bath environment. Subsequently, 3.3 mL of acryloyl chloride was slowly added dropwise, and the reaction continued to stir at low temperature for 4 h. After the reaction was completed, it was acidified with 6 mol / L hydrochloric acid, precipitated, filtered by suction, washed and dried under vacuum to obtain a pale yellow powder; S3: 3 g of the white powder and 2.1 g of the pale yellow powder were added to 11 mL of deionized water, then 1.4 g of sodium hydroxide was added, and then 0.025 g of ammonium persulfate and 0.004 g of methylene bisacrylamide were added, stirred and dissolved, and added to a mold, and heated and reacted at 65 °C for 5 h to obtain the additive.

[0033] This example discloses a preparation method of a highly biocompatible medical polycarbonate, including the following steps: Step 1: 11 g of bisphenol A was added to 105 mL of dichloromethane, stirred, and then 5.4 g of phosgene was introduced in a low-temperature environment of 2 °C for 2 h. After the introduction was completed, 1.2 mL of triethylamine was added, and the reaction continued to stir at low temperature for 4 h to obtain a prepolymer; Step 2: Add 3 g of modified polycaprolactone into 55 mL of dichloromethane, stir, and then slowly add it into 23 mL of prepolymer. Continue to stir and react at 15 °C for 2 h. After the reaction is completed, a modified prepolymer is obtained. Step 3: Add 1.5 g of auxiliary agent into 45 mL of deionized water. After stirring, add it into 19 g of modified prepolymer. Use a high-speed homogenizer to emulsify for 15 min, then add 0.6 mL of triethylamine, and continue to react for 2 h. After the reaction is completed, add ethanol, wash, dry, dissolve, precipitate, filter, and dry to obtain a highly biocompatible medical polycarbonate.

[0034] Example 5: This example discloses a preparation method of modified polycaprolactone, including the following steps: Q1: Add 1.03 g of lactobionic acid into a container containing a mixed solution of 11 mL of tetramethylethylenediamine and 16 mL of hydrochloric acid. After stirring and dissolving, add 0.061 g of N-hydroxysuccinimide and 0.26 g of EDC hydrochloride. Stir and react in a 30 °C water bath in the dark for 45 min. Then add 0.46 g of polylysine and continue to stir and react in the dark for 36 h. After the reaction is completed, dialyze for 72 h and freeze-dry for 48 h to obtain Product 1. Q2: Add calcium hydride into ε-caprolactone, mix well and let it stand, then rotary evaporate and distill under reduced pressure to obtain dehydrated ε-caprolactone. Add 6.5 g of hydroxyl-terminated polybutadiene, 11 g of dehydrated ε-caprolactone and 0.24 g of stannous octoate into a container filled with argon. Stir and react in an oil bath at 110 °C for 24 h. After the reaction is completed, cool, dissolve the product with dichloromethane, add methanol for precipitation, wash, and dry to obtain Product 2. Q3: Add 7.2 g of Product 1, 16.2 g of Product 2 and 3.1 g of lactide into a container containing 14 mL of dichloromethane. Evacuate the air, then add 0.71 mL of 1,8-diazabicyclo[5.4.0]undec-7-ene, and stir and react at room temperature for 12 h. After the reaction is completed, add benzoic acid, precipitate, wash, and dry under vacuum to obtain modified polycaprolactone.

[0035] This example discloses a preparation method of an auxiliary agent, including the following steps: S1: Add 7.8 g of glutamic acid, 70 mL of deionized water, 16 g of potassium carbonate and 30 mL of diethyl ether into a container. Stir vigorously in an ice bath environment, and then use a constant pressure dropping funnel to drop a mixed solution of 9.5 mL of acryloyl chloride and 20 mL of diethyl ether into the container. Stir and react at room temperature for 3 h. After the reaction is completed, add a 2 mol / L sodium hydroxide solution to adjust the pH to 12, extract with ethyl acetate, dry with anhydrous sodium sulfate, rotary evaporate, concentrate, and dry to obtain a white powder. S2: Add 7.5 g of phenylalanine, 4.1 g of sodium hydroxide and 45 mL of deionized water into a container, stir vigorously in an ice bath environment, then slowly dropwise add 4.1 mL of acryloyl chloride, continue stirring and reacting at low temperature for 4 h. After the reaction ends, acidify with 6 mol / L hydrochloric acid, precipitate, filter by suction, wash, and dry in vacuum to obtain a pale yellow powder; S3: Add 4 g of white powder and 4.1 g of pale yellow powder into 14 mL of deionized water, then add 1.6 g of sodium hydroxide, then add 0.035 g of ammonium persulfate and 0.006 g of methylene bisacrylamide, stir and dissolve, add into a mold, heat and react at 65 °C for 5 h to obtain an auxiliary agent.

[0036] This example discloses a preparation method of a highly biocompatible medical polycarbonate, including the following steps: Step 1: Add 12 g of bisphenol A into 115 mL of dichloromethane, stir, then introduce 6.2 g of phosgene at a low temperature of 2 °C for 2 h. After the introduction is completed, add 1.6 mL of triethylamine, and continue stirring and reacting at low temperature for 4 h to obtain a prepolymer; Step 2: Add 4 g of modified polycaprolactone into 70 mL of dichloromethane, stir, then slowly add it into 26 mL of prepolymer, and continue stirring and reacting at 15 °C for 2 h. After the reaction ends, obtain a modified prepolymer; Step 3: Add 2.5 g of auxiliary agent into 35 mL of deionized water, stir, then add it into 22 g of modified prepolymer, emulsify with a high-speed homogenizer for 15 min, then add 0.9 mL of triethylamine, continue reacting for 2 h. After the reaction ends, add ethanol, wash, dry, dissolve, precipitate, filter, and dry to obtain a highly biocompatible medical polycarbonate.

[0037] Comparative Example 1: Compared with Example 1, in the process of preparing a highly biocompatible medical polycarbonate in Comparative Example 1, modified polycaprolactone is not added, and other conditions remain unchanged.

[0038] Comparative Example 2: Compared with Example 1, in the process of preparing a highly biocompatible medical polycarbonate in Comparative Example 2, the auxiliary agent is not added, and other conditions remain unchanged.

[0039] Experimental Example: Perform performance tests on the medical polycarbonates prepared in Examples 1 - 5 and Comparative Examples 1 - 2. Test the performance of the samples according to GB / T 16886, test the mechanical properties of the samples according to GB / T 1040.1 - 2008, and test the water absorption properties of the samples according to GB / T 1034 - 2008. The test results are shown in Table 1: Table 1

[0040] As can be seen from the test results in Table 1, the medical polycarbonates prepared in Examples 1-5 of the present invention have excellent biocompatibility, mechanical properties and hydrophilic properties. By comparing Comparative Example 1 with Examples 1-5, it can be seen that adding modified polycaprolactone can effectively improve the biocompatibility, mechanical properties and hydrophilic properties of medical polycarbonates; by comparing Comparative Example 2 with Examples 1-5, it can be seen that adding additives can effectively improve the biocompatibility, mechanical properties and hydrophilic properties of medical polycarbonates.

[0041] As mentioned above, the above are only the preferred specific embodiments of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention, according to the technical solution of the present invention and its inventive concept, making equivalent substitutions or changes should be covered within the protection scope of the present invention.

[0042] The preferred embodiments of the present invention disclosed above are only used to help illustrate the present invention. The preferred embodiments do not describe all the details in detail, nor do they limit the present invention to the specific embodiments only. Obviously, many modifications and variations can be made according to the content of this specification. These embodiments are selected and specifically described in this specification in order to better explain the principles and practical applications of the present invention, so that those skilled in the art in the relevant technical field can understand and utilize the present invention well. The present invention is only limited by the claims and their full scope and equivalents.

Claims

1. A preparation method of a highly biocompatible medical polycarbonate, characterized in that, It includes the following steps: Step 1: Add bisphenol A into dichloromethane, stir, then introduce phosgene under a low-temperature environment. After the introduction is completed, add triethylamine, and continuously stir and react at low temperature to obtain a prepolymer; Step 2: Add modified polycaprolactone into dichloromethane, stir, then slowly add it into the prepolymer, and continue to stir and react. After the reaction is completed, a modified prepolymer is obtained; Step 3: Add the auxiliary agent into deionized water, stir, then add it into the modified prepolymer. After emulsification treatment, add triethylamine and continue the reaction. After the reaction is completed, add ethanol, wash, dry, dissolve, precipitate, filter, and dry to obtain a highly biocompatible medical polycarbonate.

2. The preparation method of a highly biocompatible medical polycarbonate according to claim 1, characterized in that, In the said Step 1, the dosage ratio of bisphenol A, dichloromethane, phosgene and triethylamine is (10 - 13) g : (100 - 120) mL : (5.2 - 6.5) g : (1 - 1.8) mL, the temperature of the low-temperature environment is 0 - 5 °C, the introduction time is 1 - 2 h, and the stirring reaction time is 2 - 4 h.

3. The preparation method of a highly biocompatible medical polycarbonate according to claim 1, characterized in that, The preparation method of the said modified polycaprolactone includes the following steps: Q1: Add lactobionic acid into a container containing a mixed solution of tetramethylethylenediamine and hydrochloric acid, stir and dissolve, then add N-hydroxysuccinimide and EDC hydrochloride, stir and react under water bath in the dark. Subsequently, add polylysine and continue to stir and react in the dark. After the reaction is completed, dialyze and freeze-dry to obtain Product 1; Q2: Add calcium hydride into ε-caprolactone, mix well and let it stand, rotary evaporate, and perform vacuum distillation to obtain dehydrated ε-caprolactone; Add hydroxyl-terminated polybutadiene, dehydrated ε-caprolactone and stannous octoate into a container filled with argon, and stir and react under oil bath. After the reaction is completed, cool, dissolve the product, precipitate, wash, and dry to obtain Product 2; Q3: Add Product 1, Product 2 and lactide into a container containing dichloromethane, evacuate, then add 1,8-diazabicyclo[5.4.0]undec-7-ene, stir and react at room temperature. After the reaction is completed, add benzoic acid, precipitate, wash, and vacuum dry to obtain modified polycaprolactone.

4. The preparation method of a highly biocompatible medical polycarbonate according to claim 3, characterized in that, In the said Q1, the dosage ratio of lactobionic acid, tetramethylethylenediamine, hydrochloric acid, N-hydroxysuccinimide, EDC hydrochloride and polylysine is (0.92 - 1.08) g : (8 - 12) mL : (10 - 18) mL : (0.056 - 0.063) g : (0.22 - 0.28) g : (0.42 - 0.48) g, the temperature of stirring and reacting under water bath in the dark is 30 - 35 °C, the reaction time is 30 - 45 min, the continuous stirring reaction time in the dark is 30 - 42 h, the dialysis time is 70 - 85 h, and the freeze-drying time is 42 - 50 h.

5. The preparation method of a highly biocompatible medical polycarbonate according to claim 3, wherein, In Q2, the dosage ratio of hydroxyl-terminated polybutadiene, Ɛ-caprolactone after water removal, and stannous octoate is (5 - 7) g : (8 - 12) g : (0.2 - 0.25) g. The oil bath stirring reaction temperature is 110 - 130 °C, the reaction time is 20 - 24 h. The product is dissolved in dichloromethane and methanol is added for precipitation; in Q3, the dosage ratio of product 1, product 2, lactide, dichloromethane, and 1,8-diazabicyclo[5.4.0]undec-7-ene is (5 - 8.7) g : (11 - 18.5) g : (2 - 3.5) g : (10 - 15) mL : (0.52 - 0.85) mL, and the room temperature stirring reaction time is 8 - 12 h.

6. The preparation method of a highly biocompatible medical polycarbonate according to claim 1, characterized in that, In the second step, the dosage ratio of modified polycaprolactone, dichloromethane, and prepolymer is (2 - 5) g : (50 - 75) mL : (22 - 28) mL. The continued stirring reaction time is 1 - 2 h, and the stirring temperature is 10 - 20 °C.

7. The preparation method of a highly biocompatible medical polycarbonate according to claim 1, characterized in that, The preparation method of the auxiliary agent includes the following steps: S1: Glutamic acid, deionized water, potassium carbonate, and diethyl ether are added to a container and stirred vigorously in an ice bath environment. Then, a mixed solution of acryloyl chloride and diethyl ether is added dropwise to the container using a constant pressure dropping funnel, and stirred at room temperature for reaction. After the reaction, sodium hydroxide solution is added to adjust the pH, extracted, dried, rotary evaporated, concentrated, and dried to obtain a white powder; S2: Phenylalanine, sodium hydroxide, and deionized water are added to a container and stirred vigorously in an ice bath environment. Subsequently, acryloyl chloride is slowly added dropwise, and the reaction continues with low-temperature stirring. After the reaction, it is acidified, precipitated, filtered by suction, washed, and vacuum dried to obtain a light yellow powder; S3: The white powder and the light yellow powder are added to deionized water, then sodium hydroxide is added, and then ammonium persulfate and methylene bisacrylamide are added, stirred and dissolved, and added to a mold for heating reaction to obtain the auxiliary agent.

8. The preparation method of a highly biocompatible medical polycarbonate according to claim 7, characterized in that in S1, the dosage ratio of glutamic acid, deionized water, potassium carbonate, and acryloyl chloride is (7 - 8) g : (60 - 100) mL : (12 - 18) g : (8 - 10) mL, the room temperature stirring reaction time is 3 - 4 h, the concentration of the sodium hydroxide solution is 2 mol / L, the pH is adjusted to 12, and extracted with ethyl acetate and dried with anhydrous sodium sulfate.

9. The preparation method of a highly biocompatible medical polycarbonate according to claim 7, characterized in that, In S2, the dosage ratio of phenylalanine, sodium hydroxide, deionized water, and acryloyl chloride is (6 - 8) g : (3 - 4.3) g : (30 - 50) mL : (3 - 4.2) mL, the low-temperature stirring reaction time is 3 - 4 h, and acidified with 6 mol / L hydrochloric acid; in S3, the dosage ratio of the white powder, the light yellow powder, deionized water, sodium hydroxide, ammonium persulfate, and methylene bisacrylamide is (2 - 5) g : (2 - 4.3) g : (10 - 15) mL : (1.3 - 1.8) g : (0.02 - 0.04) g : (0.003 - 0.006) g, the heating reaction temperature is 60 - 70 °C, and the time is 3 - 5 h.

10. The preparation method of a highly biocompatible medical polycarbonate according to claim 1, characterized in that, In the third step, the dosage ratio of the auxiliary agent, deionized water, modified prepolymer and triethylamine is (1 - 3) g : (30 - 50) mL : (18 - 25) g : (0.5 - 1) mL. It is emulsified by a high-speed homogenizer for 10 - 15 min, and the continuous reaction time is 1 - 2 h.

Images