阅读说明：本技术 一种利用可降解复合材料制作妇产科节育环的方法 (Method for manufacturing birth control ring for obstetrics and gynecology department by utilizing degradable composite material ) 是由 孙玉燕 崔雪立 孙晓瑛 于 2020-04-07 设计创作，主要内容包括：本发明公开了一种利用可降解复合材料制作妇产科节育环的方法,其特征在于,包括如下步骤：步骤S1、端乙烯基超支化聚碳酸酯的制备；步骤S2、β-氯乳酸离子化丙烯酸二甲胺基乙酯；步骤S3、节育环的成型。本发明还提供了一种根据所述利用可降解复合材料制作妇产科节育环的方法制作得到的妇产科节育环。本发明生产得到的妇产科节育环生物相容性好,体内降解吸收效果好,无需再次手术取出,能有效防止炎症产生；机械力学性能优异,在子宫内停留时间长,疼痛感较低,性能稳定性佳,不容易脱落。(The invention discloses a method for manufacturing a birth control ring for obstetrics and gynecology department by utilizing degradable composite materials, which is characterized by comprising the following steps: step S1, preparing vinyl-terminated hyperbranched polycarbonate; step S2, ionizing beta-chlorolactic acid into dimethylaminoethyl acrylate; and step S3, molding the contraceptive ring. The invention also provides the intrauterine device for gynaecology and obstetrics, which is manufactured by the method for manufacturing the intrauterine device for gynaecology and obstetrics by utilizing the degradable composite material. The intrauterine device for obstetrics and gynecology department produced by the invention has good biocompatibility and good in-vivo degradation and absorption effect, does not need to be taken out again for operation, and can effectively prevent inflammation; excellent mechanical property, long retention time in uterus, low pain, good performance stability and difficult shedding.)

1. A method for manufacturing a birth control ring for obstetrics and gynecology department by utilizing degradable composite materials is characterized by comprising the following steps:

step S1, preparation of vinyl-terminated hyperbranched polycarbonate: dissolving hydroxyl-terminated hyperbranched polycarbonate and cinnamic acid in a high-boiling point solvent, adding 4-dimethylaminopyridine and 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride into the solvent, stirring the mixture at the temperature of between 30 and 40 ℃ for reacting for 8 to 12 hours, precipitating the mixture in water, washing the precipitated polymer for 3 to 7 times by using ethanol, and performing rotary evaporation to remove the ethanol to obtain vinyl-terminated hyperbranched polycarbonate;

Step S2, ionizing beta-chlorolactic acid into dimethylamino ethyl acrylate: adding beta-chlorolactic acid and dimethylaminoethyl acrylate into ethyl acetate, stirring and reacting for 4-6 hours at the temperature of 30-40 ℃, and then performing rotary evaporation to remove the ethyl acetate to obtain beta-chlorolactic acid ionized dimethylaminoethyl acrylate;

step S3, molding of the contraceptive ring: adding the vinyl-terminated hyperbranched polycarbonate prepared in the step S1, the beta-chlorolactic acid ionized dimethylaminoethyl acrylate prepared in the step S2, methyl 3- (trimethylsiloxy) crotonate, allyl-beta-cyclodextrin, mesoporous silicon, 2-acrylic acid-hexahydro-4, 7-methylene-1H-indenyl ester, hyaluronic acid and an initiator into a reaction kettle, starting a stirring device to ensure that the materials in the reaction kettle are uniformly mixed, then heating and stirring the obtained mixed material in the atmosphere of nitrogen or inert gas, then placing the product in a mold, controlling the temperature of mold heating to be 170-190 ℃ under vacuum, preserving heat for 10-20min, then cooling at room temperature, aging, sterilizing and disinfecting according to the requirements of medical treatment and health after preparing a finished product, and preparing the birth control ring for the obstetrics and gynecology department.

2. The method of claim 1, wherein the hydroxyl-terminated hyperbranched polycarbonate, cinnamic acid, high boiling point solvent, 4-dimethylaminopyridine, and 1-ethyl- (3-dimethylaminopropyl) carbonyldiimine hydrochloride are used in a molar ratio of 1 (3-5) to (15-25) to (0.5-0.8) to 0.5 in step S1.

3. The method of claim 1, wherein the high boiling point solvent is at least one of dimethylsulfoxide, N-dimethylformamide, N-dimethylacetamide and N-methylpyrrolidone.

4. The method for manufacturing the intrauterine device for gynaecology and obstetrics by using the degradable composite material according to claim 1, wherein the molar ratio of the beta-chlorolactic acid, the dimethylaminoethyl acrylate and the ethyl acetate in the step S2 is 1:1 (6-10).

5. The method for preparing a birth control ring for obstetrics and gynecology department by using degradable composite material as claimed in claim 1, wherein the mass ratio of the vinyl-terminated hyperbranched polycarbonate, beta-chlorolactic acid ionized dimethylaminoethyl acrylate, methyl 3- (trimethylsiloxy) crotonate, allyl betacyclodextrin, mesoporous silicon, 2-acrylic acid-hexahydro-4, 7-methylene-1H-indenyl ester, hyaluronic acid and initiator is 3:0.5:1 (0.2-0.3):0.2:0.3:0.2 (0.05-0.06).

6. The method of claim 1, wherein the initiator is at least one of azobisisobutyronitrile and azobisisoheptonitrile.

7. The method for manufacturing an intrauterine device for obstetrics and gynecology department using degradable composite material according to claim 1, wherein the pore size of the mesoporous silicon is 2-10 nm.

8. The method as claimed in claim 1, wherein the inert gas is any one of helium, neon and argon.

9. The method for manufacturing the intrauterine device for obstetrics and gynecology department by using the degradable composite material as claimed in claim 1, wherein the heating and stirring are specifically as follows: the first stage temperature is 95-105 ℃, the stirring speed is 200-260rpm, and the stirring time is 1-2 hours; the second-stage temperature is 125-135 ℃, the stirring speed is 150-220rpm, and the stirring time is 2-3 hours; the temperature of the third section is 190 ℃ and 270 ℃, the stirring speed is 100 ℃ and 130rpm, and the stirring time is 3-5 hours.

10. An intrauterine device for obstetrics and gynecology manufactured by the method for manufacturing the intrauterine device for obstetrics and gynecology using degradable composite material according to any one of claims 1 to 9.

Technical Field

The invention relates to the technical field of biomedical materials, in particular to a method for manufacturing a birth control ring for obstetrics and gynecology department by utilizing a degradable composite material.

Background

The appearance of the contraceptive device enables the traditional relationship among marriage, sex and birth to be broken down, and the female can be relieved from the difficulty of birth, thereby obtaining higher sexual freedom. An intrauterine device is a common contraceptive device, which is placed in the uterine cavity, since the devices used in the early stages are mostly ring-shaped, also called contraceptive rings. The contraceptive ring has less interference to the whole body, acts on local parts, does not influence the fertility after being taken out, has the advantages of safety, effectiveness, reversibility, simplicity, economy and the like, and is one of the most common contraceptive tools at present. The effective rate of the intrauterine contraceptive adopted reaches 90 percent.

At present, the materials of the intrauterine device clinically applied to the uterine cavity mainly comprise metal copper and the like, and because the metal copper can not be degraded, the intrauterine device made of the copper is taken out through a secondary operation after the function of human tissue is recovered after the intrauterine device is in the uterine cavity for a period of time, and because the intrauterine device exists in the body for a long time, seroma, foreign body reaction and the like are easy to cause. Meanwhile, if the intrauterine device made of the material is too long in the uterine cavity of a human body, the intrauterine device is easily coated by uterine cavity tissues, great difficulty is brought to the secondary operation taking out, the pain of the patient is greatly increased, the treatment effect is greatly reduced, and local anaphylactic reaction or inflammation is easily caused. Other contraceptive rings on the market have the defects of unsmooth property, poor softness and elasticity, irritation when being contacted with a human body, combination with the human body when being contacted with the human body, bleeding, pain and the like.

The degradable composite material is a biomass composite material prepared by blending, extruding, hot-pressing, injection molding and other processes of natural plant fibers and biodegradable bioplastic, is environment-friendly, has good biocompatibility with human tissues, and meets the requirements of materials for preparing contraceptive rings. The current development trend is to use degradable composite materials to manufacture the birth control ring of the obstetrics and gynecology department.

The Chinese patent with application number 201710382025.6 discloses a method for manufacturing a birth control ring for obstetrics and gynecology department by using degradable composite material, belonging to the technical field of biomedical materials. The gynecological contraceptive ring is prepared from the following raw materials in parts by weight: 68.5-98.5 parts of degradable composite material, 3.3-5.7 parts of compatilizer, 22.5-44.5 parts of toughener, 0.6-1.4 parts of antioxidant and 1.7-4.7 parts of coupling agent. The formula of the invention consists of a plurality of inorganic components and a plurality of organic components, ensures the cohesiveness of the composite material, has comprehensive functions, effectively prolongs the service life of the prepared gynecological contraceptive ring, and increases the service life by 19.8-26.7 percent compared with the service life of the common contraceptive ring. The intrauterine device has the advantages that the intrauterine device can be placed in the uterus for a longer time, the pain feeling is lower than that of the intrauterine device, the intrauterine device is not easy to fall off, the satisfaction rate reaches 83-88 percent and is improved by 12.2-18.9 percent compared with that of the intrauterine device, and the intrauterine device is suitable for popularization and use; however, the compatibility between the inorganic component and the organic component in the material is not good, which easily causes the surface of the material to be not smooth, the service time is short, and the performance stability is not good.

Therefore, the method for manufacturing the intrauterine device for the obstetrics and gynecology department by utilizing the degradable composite material is more suitable, and the manufactured intrauterine device for the obstetrics and gynecology department, which has the advantages of long service life, good biocompatibility, low pain feeling, difficult shedding and excellent mechanical property, has very important significance.

Disclosure of Invention

In view of the above, the invention aims to provide a method for manufacturing a birth control ring for obstetrics and gynecology department by using degradable composite materials, which is simple and easy to implement, low in manufacturing cost, high in manufacturing efficiency and yield and suitable for continuous large-scale production; the intrauterine device for obstetrics and gynecology department produced by the preparation method has good biocompatibility and good in-vivo degradation and absorption effect, does not need to be taken out again for operation, and can effectively prevent inflammation; excellent mechanical property, long retention time in uterus, low pain, good performance stability and difficult shedding.

In order to achieve the purpose, the invention adopts the technical scheme that:

a method for manufacturing a birth control ring for obstetrics and gynecology department by utilizing degradable composite materials is characterized by comprising the following steps:

step S1, preparation of vinyl-terminated hyperbranched polycarbonate: dissolving hydroxyl-terminated hyperbranched polycarbonate and cinnamic acid in a high-boiling point solvent, adding 4-dimethylaminopyridine and 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride into the solvent, stirring the mixture at the temperature of between 30 and 40 ℃ for reacting for 8 to 12 hours, precipitating the mixture in water, washing the precipitated polymer for 3 to 7 times by using ethanol, and performing rotary evaporation to remove the ethanol to obtain vinyl-terminated hyperbranched polycarbonate;

Step S2, ionizing beta-chlorolactic acid into dimethylamino ethyl acrylate: adding beta-chlorolactic acid and dimethylaminoethyl acrylate into ethyl acetate, stirring and reacting for 4-6 hours at the temperature of 30-40 ℃, and then performing rotary evaporation to remove the ethyl acetate to obtain beta-chlorolactic acid ionized dimethylaminoethyl acrylate;

step S3, molding of the contraceptive ring: adding the vinyl-terminated hyperbranched polycarbonate prepared in the step S1, the beta-chlorolactic acid ionized dimethylaminoethyl acrylate prepared in the step S2, methyl 3- (trimethylsiloxy) crotonate, allyl-beta-cyclodextrin, mesoporous silicon, 2-acrylic acid-hexahydro-4, 7-methylene-1H-indenyl ester, hyaluronic acid and an initiator into a reaction kettle, starting a stirring device to ensure that the materials in the reaction kettle are uniformly mixed, then heating and stirring the obtained mixed material in the atmosphere of nitrogen or inert gas, then placing the product in a mold, controlling the temperature of mold heating to be 170-190 ℃ under vacuum, preserving heat for 10-20min, then cooling at room temperature, aging, sterilizing and disinfecting according to the requirements of medical treatment and health after preparing a finished product, and preparing the birth control ring for the obstetrics and gynecology department.

Further, in the step S1, the molar ratio of the hydroxyl-terminated hyperbranched polycarbonate, the cinnamic acid, the high boiling point solvent, the 4-dimethylaminopyridine and the 1-ethyl- (3-dimethylaminopropyl) carbonyldiimine hydrochloride is 1 (3-5) to (15-25) to (0.5-0.8) to 0.5.

Preferably, the preparation method of the hydroxyl-terminated hyperbranched polycarbonate is as follows: chinese invention patent example 1 with application number 201710466507. X.

Preferably, the high boiling point solvent is at least one of dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide and N-methylpyrrolidone.

Furthermore, the mol ratio of the beta-chlorolactic acid, the dimethylaminoethyl acrylate and the ethyl acetate in the step S2 is 1:1 (6-10).

Furthermore, the mass ratio of the vinyl-terminated hyperbranched polycarbonate, beta-chlorolactic acid ionized dimethylaminoethyl acrylate, methyl 3- (trimethylsiloxy) crotonate, allyl-beta-cyclodextrin, mesoporous silicon, 2-acrylic acid-hexahydro-4, 7-methylene-1H-indenyl ester, hyaluronic acid and an initiator is 3:0.5:1 (0.2-0.3) to 0.2:0.3:0.2 (0.05-0.06).

Preferably, the initiator is at least one of azobisisobutyronitrile and azobisisoheptonitrile.

Preferably, the pore diameter of the mesoporous silicon is 2-10 nm.

Preferably, the inert gas is any one of helium, neon and argon.

Preferably, the heating and stirring are specifically as follows: the first stage temperature is 95-105 ℃, the stirring speed is 200-260rpm, and the stirring time is 1-2 hours; the second-stage temperature is 125-135 ℃, the stirring speed is 150-220rpm, and the stirring time is 2-3 hours; the temperature of the third section is 190 ℃ and 270 ℃, the stirring speed is 100 ℃ and 130rpm, and the stirring time is 3-5 hours.

Another object of the present invention is to provide a birth control ring for obstetrics and gynecology manufactured according to the method for manufacturing the birth control ring for obstetrics and gynecology by using the degradable composite material.

Adopt the produced beneficial effect of above-mentioned technical scheme to lie in:

(1) the method for manufacturing the intrauterine device for the obstetrics and gynecology department by using the degradable composite material is simple and easy to implement, low in manufacturing cost, high in manufacturing efficiency and yield and suitable for continuous large-scale production.

(2) The method for manufacturing the intrauterine device for the obstetrics and gynecology department by using the degradable composite material overcomes the defects that the intrauterine device on the market is more or less non-degradable, needs to be taken out by secondary operation, is not smooth, has poor softness and elasticity, has irritation when being contacted with a human body, can be combined with the human body when being contacted with the human body, can cause bleeding, pain and the like, has good biocompatibility and good in-vivo degradation absorption effect, does not need to be taken out by secondary operation, and can effectively prevent inflammation; excellent mechanical property, long retention time in uterus, low pain, good performance stability and difficult shedding.

(3) The invention provides a method for preparing a birth control ring for obstetrics and gynecology department by using degradable composite materials, wherein a base material is prepared by free radical polymerization of vinyl-containing monomer-terminated vinyl hyperbranched polycarbonate, beta-chlorolactic acid ionized dimethylaminoethyl acrylate, methyl 3- (trimethylsiloxy) crotonate, allyl-beta cyclodextrin and 2-acrylic acid-hexahydro-4, 7-methylene-1H-indenyl ester, the materials are reasonable in material selection, good in biocompatibility and biodegradable, and the performance advantages of the structures of polycarbonate, lactic acid, aminoethyl, siloxy crotonate, cyclodextrin and indenyl ester are combined, so that the birth control ring is strong in biodegradability, fast in degradation period and excellent in biocompatibility; the introduction of the hyperbranched structure improves the compatibility of the polycarbonate with other components, improves the antibacterial property of the polycarbonate by improving the introduction of the cinnamic acid structure, and provides a reaction site for subsequent crosslinking reaction.

(4) According to the method for manufacturing the intrauterine device for the obstetrics and gynecology department, provided by the invention, the manufactured intrauterine device for the obstetrics and gynecology department forms a three-dimensional cross-linked network structure through copolymerization reaction in the forming stage, so that the mechanical property is better, the comprehensive property is more excellent, the intrauterine device stays in uterus for a long time, and the performance stability is better.

(5) According to the method for manufacturing the intrauterine device for the obstetrics and gynecology department by using the degradable composite material, the indenyl ester structure introduced into the manufactured intrauterine device for the obstetrics and gynecology department can ensure the interface bonding performance of the composite material on the premise of ensuring good biocompatibility and degradation performance, the functions are comprehensive, a small molecule coupling agent is not required to be additionally added, and the service life of the intrauterine device is effectively prolonged; the methyl 3- (trimethylsiloxy) crotonate structure is introduced to be cooperated with the hyaluronic acid structure, so that the lubricity of the crotonate structure can be improved, the surface is smooth, and the pain is reduced; the added mesoporous silicon also has better degradation performance, and can improve the mechanical strength after being added, and the mesoporous structure is beneficial to the bonding of the mesoporous silicon and inorganic components, so that the performance stability of the mesoporous silicon is better; the quaternary ammonium salt structure is introduced to improve the antibacterial property, and the hyaluronic acid radical ions are easily connected with quaternary ammonium salt cations by ionic bonds, so that the comprehensive performance is further improved.

Detailed Description

In order to make the technical solutions of the present invention better understood and make the above features, objects, and advantages of the present invention more comprehensible, the present invention is further described with reference to the following examples. The examples are intended to illustrate the invention only and are not intended to limit the scope of the invention.

In the embodiment of the invention, the raw materials are all purchased commercially; the preparation method of the hydroxyl-terminated hyperbranched polycarbonate is as follows: chinese invention patent example 1 with application number 201710466507. X.