阅读说明：本技术 一种改性聚丙烯酸共聚物及其制备方法和应用 (Modified polyacrylic acid copolymer and preparation method and application thereof ) 是由 周菊英 廖华珍 赵彦芝 李庆 黄钦 雷福厚 于 2020-07-24 设计创作，主要内容包括：本发明提供了一种改性聚丙烯酸共聚物及其制备方法和应用,通过将左旋海松醇、聚丙烯酸和催化剂溶解于有机溶剂中,在氮气环境下,温度控制在10℃下,加入偶联剂密封反应,反应完成后去除溶剂,用无水乙醇透析,得到左旋海松醇接枝改性聚丙烯酸共聚物。该共聚物生物相容性好,具有两亲性,且pH响应性可调,可用于负载杨梅素等中草药并实现在不同pH下的释药。(The invention provides a modified polyacrylic acid copolymer and a preparation method and application thereof, which are characterized in that levo-pinitol, polyacrylic acid and a catalyst are dissolved in an organic solvent, a coupling agent is added for sealing reaction under the nitrogen environment and at the temperature of 10 ℃, the solvent is removed after the reaction is finished, and absolute ethyl alcohol is used for dialysis, so that the levo-pinitol graft modified polyacrylic acid copolymer is obtained. The copolymer has good biocompatibility, amphipathy and adjustable pH responsiveness, and can be used for loading Chinese herbal medicines such as myricetin and the like and realizing drug release under different pH values.)

1. A modified polyacrylic acid copolymer, wherein the modified polyacrylic acid copolymer is represented by formula (I):

2. the method for preparing modified polyacrylic acid copolymer according to claim 1, wherein the levopimaric alcohol, the polyacrylic acid and the catalyst are dissolved in an organic solvent, the temperature is controlled at 10 ℃ in a nitrogen environment, a coupling agent is added for sealing reaction, the solvent is removed after the reaction is completed, and the levopimaric alcohol graft modified polyacrylic acid copolymer is obtained by dialysis with absolute ethyl alcohol;

wherein the structural formula of the levo-pinitol is shown as the formula (II):

3. the method according to claim 2, wherein the catalyst is selected from 4-dimethylaminopyridine, the organic solvent is a mixed solution of chloroform and tetrahydrofuran, and the coupling agent is selected from ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride.

4. The preparation method according to claim 2, wherein the sealing reaction by adding the coupling agent is specifically: after the reaction was carried out for 1 hour, the temperature was raised to 40 ℃ to carry out the reaction for 72 hours.

5. The method of claim 2, wherein said levo-pinitol is prepared by the following method: and (2) sequentially dropwise adding the tetrahydrofuran solution of the levopimaric acid and iodine into the tetrahydrofuran solution of the sodium borohydride at room temperature, taking the lower layer solution for rotary distillation, dissolving the obtained dope by using petroleum ether, taking the upper layer solution for liquid separation, taking the upper layer solution for dewatering, filtering to obtain filtrate, and carrying out rotary distillation to obtain the levopimaric alcohol shown in the formula (II).

6. Use of the modified polyacrylic copolymer of claim 1 as a pharmaceutical carrier.

Technical Field

The invention belongs to the technical field of modified copolymers, and particularly relates to a modified polyacrylic copolymer and a preparation method and application thereof.

Background

The polymer drug delivery system is characterized in that a polymer carrier is used for coating, adsorbing or chemically connecting drugs, the drugs are delivered to a focus part by using the characteristics of the drug carrier such as selective distribution, physicochemical property and the like, and the drugs can be slowly released by diffusion and the like, so that the aim of safely and effectively treating diseases is fulfilled. However, the use of some medicinal polymer materials is restricted by biocompatibility, biodegradability and safety, and the development of safe polymer materials with novel functions is always a hot field of pharmaceutical research.

Nanoparticles having a core-shell structure can be formed by self-assembly of amphiphilic polymers in aqueous solution. Wherein the hydrophilic shell serves as a physical barrier preventing interaction between the nanoparticles, thereby ensuring stability of the nanoparticles; the hydrophobic core provides a storage of insoluble drugs by utilizing the lipophilic segment, thereby increasing the drug loading rate and realizing the function of protecting the drugs. Polyacrylic acid contains a large amount of carboxyl, has excellent hydrophilicity and biocompatibility, has the characteristic of easy modification, and is widely applied to the field of drug sustained release.

Disclosure of Invention

Aiming at the existing problems, the invention provides a modified polyacrylic acid copolymer and a preparation method and application thereof.

In order to achieve the technical purpose, the invention is specifically realized by the following technical scheme:

a modified polyacrylic acid copolymer, wherein the modified polyacrylic acid copolymer is represented by formula (I):

wherein m is 1-100, and n is 1-100.

In another aspect of the present invention, there is provided a method for preparing the modified polyacrylic acid copolymer, comprising the steps of: dissolving levo-pinitol, polyacrylic acid and a catalyst in an organic solvent, adding a coupling agent for sealing reaction under the nitrogen environment and at the temperature of 10 ℃, removing the solvent after the reaction is finished, and dialyzing with absolute ethyl alcohol to obtain a levo-pinitol grafted and modified polyacrylic acid copolymer;

wherein the structural formula of the levo-pinitol is shown as the formula (II):

further, the catalyst is selected from 4-dimethylamino pyridine, the organic solvent is a mixed solution of chloroform and tetrahydrofuran, and the coupling agent is selected from ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride.

Further, the sealing reaction by adding the coupling agent specifically comprises the following steps: after the reaction was carried out for 1 hour, the temperature was raised to 40 ℃ to carry out the reaction for 72 hours.

Further, the levo-pinitol is prepared by the following method: and (2) sequentially dropwise adding the tetrahydrofuran solution of the levopimaric acid and iodine into the tetrahydrofuran solution of the sodium borohydride at room temperature, taking the lower layer solution for rotary distillation, dissolving the obtained dope by using petroleum ether, taking the upper layer solution for liquid separation, taking the upper layer solution for dewatering, filtering to obtain filtrate, and carrying out rotary distillation to obtain the levopimaric alcohol shown in the formula (II).

In another aspect of the invention, the modified polyacrylic copolymer is also provided for use as a drug carrier.

The invention has the beneficial effects that:

the levo-pinitol graft modified polyacrylic acid copolymer obtained by the one-step esterification method has good biocompatibility, amphipathy and adjustable pH responsiveness, and can be used for loading Chinese herbal medicines such as myricetin and the like and realizing drug release under different pH values.

Drawings

FIG. 1 is a transmission electron microscope picture of levo-pinitol grafted polyacrylic acid micelle of the present invention;

FIG. 2 is a plot of L-pinitol grafted polyacrylic acid resonance light scattering intensity versus pH in accordance with the present invention;

FIG. 3 shows the release rates of myricetin loaded by the levo-pinoresinol grafted polyacrylic copolymer of the present invention at different pH values.

Detailed Description

The technical solutions of the present invention will be described clearly and completely with reference to specific embodiments of the present invention, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.