WO2017185218A1

WO2017185218A1 - Method for preparing hydrophilic polycaprolactone film

Info

Publication number: WO2017185218A1
Application number: PCT/CN2016/080180
Authority: WO
Inventors: 王海朋; 李战雄
Original assignee: 苏州大学张家港工业技术研究院
Priority date: 2016-04-25
Filing date: 2016-04-25
Publication date: 2017-11-02

Abstract

Disclosed in the present invention is a method for preparing a hydrophilic polycaprolactone film, the method comprising: introducing an oxime group to a polycaprolactone pendant group; subjecting a succinic anhydride to esterification with a hydroxyl group in a sideoxime group so as to obtain a carboxylated polycaprolactone; and then reacting a terminal hydroxyl polyethylene glycol with a carboxyl, and grafting the polyethylene glycol to a polycaprolactone side chain so as to obtain a hydrophilic polycaprolactone; and preparing a hydrophilic polycaprolactone film by using solution coating. According to the present invention, the interior of a hydrophilically-modified polycaprolactone material body is also changed from hydrophobic to hydrophilic so as to obtain a modified product having a high grafting rate and a high hydrophilicity. Meanwhile, the preparation method disclosed in the present invention has the advantages of mild reaction conditions, simple preparation processes and strong controllability, and is suitable for industrial production.

Description

Title of the invention: Preparation method of hydrophilic polycaprolactone film

Technical field

[0001] The present invention relates to a method for preparing a hydrophilic polyester material, and more particularly to a method for preparing a polyethylene glycol grafted polycaprolactone hydrophilic film.

Background technique

[0002] Polycaprolactone (PCL) is a linear aliphatic polyester obtained by ring-opening polymerization of ω-caprolactone monomer catalyzed by a metal organic compound such as tetraphenyltin. Excellent biodegradability, good biocompatibility, drug permeability and mechanical properties have been certified by the US FDA and have been widely studied and applied in the field of film applications. The polycaprolactone (PCL) has a melting point of 59 to 64 ° C and a glass transition temperature of -60 ° C. Its structural repeat unit has 5 non-polar methylene-CH ₂ - and one polar ester group -COO-, 艮P-(C00CHCH ₂ CH ₂ CH ₂ CH ₂ CH ₂ -)Pn, such a structure PCL has good flexibility and processability, and it has good biocompatibility.

[0003] However, it has been found during research and use that polycaprolactone is used as a biomaterial. Due to the high hydrophobicity of polycaprolactone, its macromolecular backbone lacks reactive functional groups, thus causing it to be in organisms. The degradation rate is still not ideal, which limits the wide application of polycaprolactone in the biomedical field. In order to overcome the above disadvantages, it is often used to copolymerize ω-caprolactone monomer with other monomers, and a hydrophilic group is introduced into the copolymer to realize functional group modification of polycaprolactone, and the method has problems. It complicates the preparation process and makes the product quality control more difficult.

technical problem

[0004] Therefore, people have turned to the surface activation and surface hydrophilic modification methods to improve the hydrophilicity of polycaprolactone products, for example, after the surface of the polycaprolactone material is irradiated to generate free radicals, the vinyl monomer is used as the surface. The modifier is grafted onto the surface of the polymer to achieve the purpose of modification. When so modified, radiation often causes the polycaprolactone backbone to break or crosslink, alter the chemical structure of such polymers, and sometimes even deteriorate the quality of the product; moreover, the method of surface modification introduces hydrophilic and other functional groups. There are disadvantages such as insufficient modification amount, difference in surface treatment layer from inside material and material body.

Problem solution Technical solution

[0005] The present invention introduces a hydrophilic graft chain on a polycaprolactone macromolecular side group by a chemoselective method to obtain a graft-modified polycaprolactone. The synthetic route is simple, the reaction conditions are mild and efficient, and the main chain structure of the polycaprolactone macromolecule is not destroyed, thereby obtaining a hydrophilic film material uniformly modified by the bulk of the polycaprolactone.

[0006] In order to achieve the above object, the technical solution of the present invention is: A method for preparing a hydrophilic polycaprolactone film, comprising the following steps:

[0007] (1) Dissolving polycaprolactone into an ether solvent, and then adding an amino alcohol reaction, after the reaction is completed, the reaction liquid is poured into an anti-solvent, and then filtered to obtain a solid, that is, hydroxylated polycaprolactone;

[0008] (2) dissolving the hydroxylated polycaprolactone into an ether solvent to obtain a hydroxylated polycaprolactone solution; adding succinic anhydride, 4-dimethylaminopyridine, anhydrous carbonate to the ether solvent The mixed solution is obtained; then the hydroxylated polycaprolactone solution is added dropwise to the mixed solution, and the reaction is completed after 0.5 to 2 hours, and then the reaction is completed; after the reaction is completed, the filtrate is filtered, and the diluted acid is added to the filtrate, and the mixture is poured and poured. In the anti-solvent, a solid is precipitated, that is, a carboxylated polycaprolactone;

[0009] (3) dissolving carboxylated polycaprolactone, hydrazine, Ν'-carbonyldiimidazole in an ether solvent to obtain a carboxylated polycaprolactone solution; dissolving PEG in an ether solvent under nitrogen protection Then, the carboxylated polycaprolactone solution is added dropwise, and the reaction is completed after 0.5 to 5 hours, and then the reaction is completed; after the reaction is completed, the reaction solution is poured into an anti-solvent to precipitate a white solid, that is, hydrophilic polycaprolactone;

[0010] (4) Dissolving hydrophilic polycaprolactone in 1,4-dioxane to prepare a solution of 5% to 35% by mass, and on a spin coater at 1000 to 8000 rpm Under spin coating, a hydrophilic polycaprolactone film was obtained.

[0011] In the above technical solution, the amino alcohol is 2-amino-1-ethanol, 4-amino-1-butanol, 6-amino-1-hexanol, 8-amino-1-octanol or 10- Amino-1-nonanol; the terminal hydroxyl polyethylene glycol is one of PEG100, PEG200, P EG400, PEG600, PEG1000, PEG 1200 ^ PEG 1600 ^ PEG2000; the ether solvent is diethyl ether, tetrahydrofuran, 1 Any one or more mixed solvents of 4-dioxane; the anti-solvent is any one or more of n-pentamidine, n-hexyl, n-glyoxime, n-octyl, and petroleum ether a mixed solvent; the dilute acid is a hydrochloric acid solution or an acetic acid solution; and the anhydrous carbonate is any one of potassium carbonate, sodium carbonate, sodium hydrogencarbonate, and potassium hydrogencarbonate.

[0012] In the above technical solution, in the step (1), the mass ratio of the amino alcohol to the polycaprolactone is (1 to 10): (1) ~5) ; In step (2), the mass ratio of succinic anhydride, hydroxylated polycaprolactone, 4-dimethylaminopyridine, anhydrous carbonate is (1~15): (1~5) : ( 0.3-3) : (2~10); In step (3), the mass ratio of the terminal hydroxyl group polyethylene glycol, carboxylated polycaprolactone, hydrazine, Ν'-carbonyldiimidazole is (1.5~15) :( 0.2~ 3) : (0.5~5).

[0013] In the above technical solution, in the step (1), the reaction temperature is 40 to 90 ° C, the reaction time is l~24h; in the step (2), the reaction temperature is 50 to 90 ° C, the reaction time is l 〜12h; In the step (3), the reaction temperature is 25 to 65 ° C, and the reaction time is 1 to 24 hours.

[0014] Preferably, the step (1) to the step (3) further includes a purification step, specifically:

[0015] Purification of hydroxylated polycaprolactone, after the reaction is completed, the reaction solution is poured into an anti-solvent, and then filtered to obtain a solid; the solid is first washed with an alcohol solvent 1 to 6 times, and then washed with deionized water 3 to 5 Secondly; finally baked at 30~45 ° C for 1~24 hours, then obtained hydroxylated polycaprolactone;

[0016] Purification of the carboxylated polycaprolactone, after the reaction is completed, the filtrate is obtained by filtration, and the dilute acid is added to the filtrate, and then mixed, poured into an anti-solvent to precipitate a solid; the solid is firstly treated with an alcohol solvent and deionized water. Mixed solvent washing 2

~3 times, then washed with deionized water 3~5 times, and finally baked at 30 ° (: ~ 65 ° C for 1~24 hours, then obtained carboxylated polycaprolactone;

[0017] Purification of hydrophilic polycaprolactone, after the reaction is completed, the reaction solution is poured into an anti-solvent to precipitate a white solid; the white solid is first washed 2~5 times with a mixed solution of an alcohol solvent and deionized water. Then, it is washed 3 to 5 times with deionized water, and finally dried at 30 ° (: ~ 65 ° C for 1 to 24 hours) to obtain hydrophilic polycaprolactone.

[0018] In the above aspect, the alcohol solvent is any one of ethanol, methanol, and isopropyl alcohol or a mixed solvent of one or more.

[0019] The chemical structural formula of the hydrophilic polycaprolactone prepared by the present invention is as follows:

[0020] wherein:

[0021] m is an integer of 1 to 1000, n is an integer of 0 to 1000, an integer of 5, and y is an integer of 100 to 2000.

[0022] Polycaprolactone (PCL) is a kind of linear aliphatic polyester obtained by ring-opening polymerization of ω-caprolactone monomer catalyzed by a metal organic compound (such as tetraphenyltin). The initiator structural unit is present at the terminal, and the present invention does not limit the type of the initiator. The initiator unit in the polycaprolactone does not affect the technical effect of the present invention.

Advantageous effects of the invention

Beneficial effect

[0023] Compared with the prior art, the technical solution provided by the present invention has the beneficial effects of:

[0024] (1) The present invention utilizes an amino alcohol-functionalized polycaprolactone for the first time to prepare a side chain hydroxylated polycaprolactone, and then introduces a carboxyl group into a side chain of a hydroxylated polycaprolactone by using succinic anhydride, and then clicks Chemically, polyethylene glycol (PEG) is grafted to the hydroxylated polycaprolactone backbone to obtain PCL-g-PEG, which is then spin-coated to prepare a hydrophilic polycaprolactone film.

[0025] (2) The hydrophilic polycaprolactone disclosed by the invention has strong hydrophilicity, and the preparation method of the public cockroach can effectively regulate the grafting density and the graft chain length of the polycaprolactone, and the preparation property is excellent. Hydrophilic graft modified polycaprolactone.

[0026] (3) The hydrophilic modification of the present invention is to modify the bulk of the polycaprolactone, and all the polycaprolactone macromolecules in the obtained modified material have been grafted with polyethylene glycol; Hydrophilic modification of the surface of polycaprolactone material The difference is that the modified polycaprolactone also changes from hydrophobic to hydrophilic, and an unexpected technical effect is obtained.

Invention embodiment

Embodiments of the invention

[0027] Embodiment 1

(1) Hydroxylated polycaprolactone

[0029] To a 100 mL three-necked flask was added 2 g of polycaprolactone and 80 g of 1,4-dioxane, heated to 50 ° C in a constant temperature oil bath, completely dissolved in polycaprolactone, added 4 g of 6-amino-1-hexanol was reacted in a closed system for 8 hours. After the reaction was completed, the reaction solution was poured into 40 g of n-hexane, and the hydroxyl-activated polycaprolactone was precipitated by an anti-solvent method, and filtered to obtain a white solid, which was washed twice with ethanol, 100 g each time, and then deionized water. Wash 5 times, using 300 _g each time. The product was then placed in a vacuum oven and baked at 37 ° C for 24 hours to give hydroxylated polycaprolactone.

(2) Carboxylated polycaprolactone

[0031] 1.75 g of succinic anhydride (SAA), 0.3 g was added to a 100 mL three-necked flask.

4-dimethylaminopyridine (DMAP), 2 g of anhydrous potassium carbonate and 30 g of dehydrogenated tetrahydrofuran (THF) were dissolved by stirring at 60 ° C, and lg-hydroxylated polycaprolactone was dissolved in 20 g of tetrahydrofuran. Under nitrogen protection, through the constant temperature and constant pressure dropping funnel, three bottles of the inlet port were added dropwise, and the mixture was dropped in 1 hour, and then at 60. The reaction was carried out at C for 12 hours. After the reaction is completed, the solid impurities are removed by filtration to obtain a reaction solution. To the solution after the reaction, a 20 g of 0% hydrochloric acid solution is added, and the mixture is shaken repeatedly, and the reaction liquid is poured into 30 g of hexamethylene ruthenium, and the carboxylated polycondensate is precipitated by an anti-solvent method. The lactone is washed 3 times with a mixed solution of ethanol and deionized water (v/v, 1:1), 100 g each time, and then washed 4 times with deionized water, 300 g each time, and the obtained product is placed. The mixture was baked in a vacuum oven at 37 ° C for 24 hours to obtain a carboxyl-activated polycaprolactone.

(3) Graft modification

[0033] To a 50 mL three-necked flask was placed 0.5 g of carboxyl-activated PCL, 0.8 g of hydrazine, Ν'-carbonyldiimidazole (CDI) and 15 g of dehydrogenated tetrahydrofuran (THF), and dissolved at room temperature. Under nitrogen protection, 1.5 g of PEG-400 was dissolved in 10 g of dehydrogenated tetrahydrofuran (THF), and added dropwise to a three-necked flask through a constant temperature and constant pressure funnel, and the addition was completed in 0.5 hour, and the reaction was carried out at 35 ° C for 8 hours. . After completion of the reaction, the reaction solution was poured into 20 g of n-hexane, and PCL of grafted PEG-400 was precipitated by an anti-solvent method, and filtered to obtain a white solid, using ethanol and deionized water. (Volume ratio 1:1) Wash the mixed solution 4 times, use 100 g each time, then wash it 4 times with deionized water, use 300 g each time, put the obtained product into a vacuum oven, and bake at 37 °C. Osmium, a polycaprolactone grafted with PEG-400, called PCL-g-PEG.

[0034] The hydrophilic polycaprolactone is dissolved in 1,4-dioxane, formulated into a 20% mass concentration solution, and spin-coated on a spin coater at 2000 rpm to obtain hydrophilicity. Polycaprolactone film. Through the static contact angle test, the static contact angle of the polycaprolactone (PCL) film is as high as 95°, and the static contact angle of the obtained PCL-g-PEG film is obtained after grafting polyethylene glycol (PEG) onto the P CL main chain. It is 38°, which indicates that the hydrophilic property of polycaprolactone (PCL) is remarkably improved by grafting a polyethylene glycol having a hydrophilic effect of a polyether segment.

[0035] Embodiment 2

(1) Hydroxylated polycaprolactone

[0037] Adding 5 g of polycaprolactone and 200 g of 1,4-dioxane to a 500 mL three-necked flask, heating to 50 ° C in a constant temperature oil bath, completely dissolving the polycaprolactone, and then adding 10 g

6-Amino-1-hexanol was reacted in a closed system for 8 hours. After the reaction was completed, the reaction solution was poured into 60 g of n-heptane, and the hydroxyl-activated polycaprolactone was precipitated by an anti-solvent method, and filtered to obtain a white solid, which was washed three times with ethanol, 200 g each time, and deionized again. The water was washed 3 times, 500 g each time, and then the product was placed in a vacuum oven and baked at 37 ° C for 24 hours to obtain a hydroxylated polycaprolactone.

(2) Carboxylated polycaprolactone

[0039] To a 250 mL three-necked flask was added 3.5 g of succinic anhydride (SAA), 0.6 g

4-dimethylaminopyridine (DMAP), 4 g of anhydrous potassium carbonate and 60 g of dehydrogenated tetrahydrofuran (THF) were dissolved by stirring at 60 ° C, and 2 g of hydroxylated polycaprolactone was dissolved in 50 g of tetrahydrofuran. Under a nitrogen atmosphere, three bottles of the inlet port were dropwise added through a constant temperature and constant pressure dropping funnel, and the mixture was dropped in one hour, and then reacted at 60 ° C for 12 hours. After the reaction was completed, the solid impurities were removed by filtration to obtain a reaction solution. To the solution after the reaction, 40 mL of a 10% acetic acid solution was added, and the mixture was shaken repeatedly, and the reaction liquid was poured into 52 _{g of} n-heptane to precipitate a carboxyl group by an antisolvent method. Polycaprolactone, washed 3 times with a mixed solution of ethanol and deionized water (v/v, 1:1), 200 g each time, and then washed 4 times with deionized water, 300 g each time, will get The product was placed in a vacuum oven and baked at 37 ° C for 24 hours to obtain carboxyl activated polycaprolactone.

(3) Graft modification

[0041] To a 100 mL three-necked flask was added 1.2 g of thiol-activated PCL, 1.92 g Ν,Ν'-carbonyldiimidazole (CDI) and 30 g of dehydrogenated tetrahydrofuran (THF) were dissolved at room temperature. Under nitrogen protection, 3 g of PEG-600 was dissolved in 20 g of dehydrogenated tetrahydrofuran (THF), and added dropwise to a three-necked flask through a constant temperature and constant pressure funnel, and the addition was completed in 1 hour, and the reaction was carried out at 35 ° C for 8 hours. . After the reaction was completed, the reaction solution was poured into 25 g of n-heptane, and PCL of grafted PEG-600 was precipitated by an anti-solvent method, and filtered to obtain a white solid, which was mixed with ethanol and deionized water (v/v, 1: 1). Wash 4 times, use 100 g each time, wash 4 times with deionized water, use 300 g each time, put the obtained product into a vacuum oven, and bake at 37 ° C for 24 hours to obtain grafted PEG-600. Polycaprolactone.

[0042] The hydrophilic polycaprolactone is dissolved in 1,4-dioxane, formulated into a 10% by mass solution, and spin-coated on a spin coater at 4000 rpm to obtain hydrophilicity. Polycaprolactone film. The static contact angle of the grafted PEG-600 polycaprolactone PCL-g-PEG film was tested by static contact angle to be 3 Γ.

[0043] Embodiment 3

(1) Hydroxylated polycaprolactone

[0045] 10 g of polycaprolactone and 250 g of tetrahydrofuran (THF) were added to a 500 mL three-necked flask, heated to 50 ° C in a constant temperature oil bath, completely dissolved in polycaprolactone, and then added to 20 g of 6- The amino-1-hexanol was reacted in a closed system for 8 hours. After the reaction, the reaction solution was poured into 120 g of petroleum ether, and the hydroxyl-activated polycaprolactone was precipitated by an anti-solvent method, and filtered to obtain a white solid, which was washed three times with methanol, 300 g each time, and then deionized water. Wash 3 times, use 600 each time

g, then the product was placed in a vacuum oven and baked at 40 ° C for 20 hours to obtain a hydroxylated polycaprolactone.

(2) Carboxylated polycaprolactone

[0047] To a 500 mL three-necked flask was added 7 g of succinic anhydride (SAA), 1.2 g.

4-dimethylaminopyridine (DMAP), 8 g of anhydrous potassium carbonate and 100 g of dehydrogenated tetrahydrofuran (THF) were dissolved by stirring at 60 ° C, and 4 g of hydroxylated polycaprolactone was dissolved in 100 g of tetrahydrofuran. Under nitrogen protection, through the constant temperature and constant pressure dropping funnel, three bottles of the inlet port were added dropwise, and 2 small drops were dropped, followed by 60. The reaction was carried out for 12 hours at C. After the completion of the reaction, the solid impurities were removed by filtration to obtain a reaction solution. To the solution after the reaction, 60 mL of a 10% hydrochloric acid solution was added, and the mixture was shaken repeatedly, and the reaction liquid was poured into 90 g of petroleum ether, and the carboxylated polycondensate was precipitated by an antisolvent method. Caprolactone, washed 3 times with methanol and deionized water (v/v, 1:1) mixed solution, 200 _g each time, and then washed 4 times with deionized water, 300 _g each time, the product obtained It was placed in a vacuum oven and baked at 37 ° C for 24 hours to obtain a carboxyl-activated polycaprolactone. (3) Graft modification

[0049] 2.4 g of carboxyl-activated PCL, 3.84 g was added to a 250 mL three-necked flask.

Ν,Ν'-carbonyldiimidazole (CDI) and 60 g of dehydrogenated tetrahydrofuran (THF) were dissolved at room temperature. Under nitrogen protection, 7.2 g of PEG-400 was dissolved in 40 g of dehydrogenated tetrahydrofuran (THF), and added dropwise to a three-necked flask through a constant temperature and constant pressure funnel, and the addition was completed in 1.5 hours at 35 ° C. Reaction for 8 hours. After the reaction was completed, the reaction solution was poured into 30 g of petroleum ether, and PCL of grafted PEG-400 was precipitated by an anti-solvent method, and filtered to obtain a white solid, which was washed with a mixed solution of methanol and deionized water (v/v, 1: 1). 4 times, use 200 g each time, then wash 4 times with deionized water, use 300 g each time, put the obtained product into a vacuum oven, and bake at 37 ° C for 24 hours to obtain the graft of grafted PEG-400. Caprolactone.

[0050] The hydrophilic polycaprolactone is dissolved in 1,4-dioxane, formulated into a 20% mass concentration solution, and spin-coated on a spin coater at 2000 rpm to obtain hydrophilicity. Polycaprolactone film. The static contact angle of the grafted polycaprolactone PCL-g-PEG film was measured by static contact angle to be 36°.

[0051] Embodiment 4

(1) Hydroxylated polycaprolactone

[0053] Adding 6 g of polycaprolactone and 150 g of 1,4-dioxane to a 500 mL three-necked flask, heating to 50 ° C in a constant temperature oil bath, completely dissolving the polycaprolactone, and then adding 12 g

6-Amino-1-hexanol was reacted in a closed system for 8 hours. After completion of the reaction, the reaction solution was poured into 80 _{g of} n-hexane, and the hydroxyl-activated polycaprolactone was precipitated by an anti-solvent method, and filtered to obtain a white solid, which was washed three times with ethanol, 200 g each time, and then deionized. The water was washed 3 times, 400 g each time, and then the product was placed in a vacuum oven and baked at 37 ° C for 24 hours to obtain hydroxylated polycaprolactone.

(2) Carboxylated polycaprolactone

[0055] To a 500 mL three-necked flask was added 8.75 g of succinic anhydride (SAA), 1.5 g.

4-dimethylaminopyridine (DMAP), 10 g of anhydrous potassium carbonate and 100 g of dehydrogenated tetrahydrofuran (THF) were dissolved by stirring at 60 ° C, and 5 g of hydroxylated polycaprolactone was dissolved in 150 g of tetrahydrofuran. Under a nitrogen atmosphere, three bottles of the inlet port were dropwise added through a constant temperature and constant pressure dropping funnel, and 2 hours of dropping were completed, followed by a reaction at 60 ° C for 12 hours. After the completion of the reaction, the solid impurities were removed by filtration to obtain a reaction solution. To the solution after the reaction, 60 mL of a 10% hydrochloric acid solution was added, and the mixture was shaken repeatedly, and the reaction liquid was poured into 125 g of n-hexane to precipitate a carboxylated polymer by an antisolvent method. Caprolactone, washed with a mixed solution of ethanol and deionized water (v/v, 1:1) 3 times, use 300 g each time, then wash 4 times with deionized water, use 400 g each time, put the obtained product into a vacuum oven, and bake at 37 ° C for 24 hours to obtain a carboxyl-activated polycap ester.

(3) Graft modification

[0057] To a 250 mL three-necked flask was placed 4 g of carboxyl-activated PCL, 6.4 g of hydrazine, Ν'-carbonyldiimidazole (CDI) and 60 g of dehydrogenated tetrahydrofuran (THF), which were dissolved at room temperature. Under nitrogen protection, 12 g of PEG-800 was dissolved in 40 g of dehydrogenated tetrahydrofuran (THF), and added dropwise to a three-necked flask through a constant temperature and constant pressure funnel. After 1.5 hours of dropwise addition, the reaction was carried out at 35 ° C for 8 hours. Inches. After the reaction was completed, the reaction solution was poured into 60 g of hexamethylene ruthenium, and PCL of grafted PEG-800 was precipitated by an anti-solvent method, and filtered to obtain a white solid, which was washed with a mixed solution of ethanol and deionized water (v/v, 1:1). 4 times, 300 per use

g, then wash 4 times with deionized water, use 400 g each time, put the obtained product into the vacuum oven, 37

The mixture was baked at ° C for 24 hours to obtain a polycaprolactone grafted with PEG-800.

[0058] The hydrophilic polycaprolactone was dissolved in 1,4-dioxane, formulated into a 20% mass concentration solution, and spin-coated on a spin coater at 2000 rpm to obtain hydrophilicity. Polycaprolactone film. The static contact angle of the grafted PEG-S00 polycaprolactone PCL-g-PEG film was measured by static contact angle to be 32°.

[0059] Embodiment 5

(1) Hydroxylated polycaprolactone

[0061] 20 g of polycaprolactone and 300 g of 1,4-dioxane were added to a 500 mL three-necked flask, heated to 50 ° C in a constant temperature oil bath, completely dissolved in polycaprolactone, and then added. 40 g of 6-amino-1-hexanol was reacted in a closed system for 8 hours. After the completion of the reaction, the reaction solution was poured into 300 g of petroleum ether, and the hydroxyl-activated polycaprolactone was precipitated by an anti-solvent method, and filtered to obtain a white solid, which was washed four times with ethanol, 500 g each time, and deionized again. The water was washed 3 times, 800 g each time, and then the product was placed in a vacuum oven and baked at 37 ° C for 24 hours to obtain a hydroxylated polycaprolactone.

(2) Carboxylated polycaprolactone

[0063] To a 500 mL three-necked flask was added 17.5 g of succinic anhydride (SAA), 3 g

4-dimethylaminopyridine (DMAP), 20 g of anhydrous potassium carbonate and 150 g of dehydrogenated tetrahydrofuran (THF) were dissolved by stirring at 60 ° C, and 10 g of theylated polycaprolactone was dissolved in 200 g of tetrahydrofuran. Under nitrogen protection, through the constant temperature and constant pressure dropping funnel, three bottles of the inlet port were added dropwise, and 4 small drops were dropped, followed by 60. The reaction was carried out for 12 hours at C. After the reaction is completed, the solid impurities are removed by filtration to obtain a reaction solution, and the solution is added to the solution after the reaction. Add 60 mL of 10% hydrochloric acid solution, shake it repeatedly, shake the reaction solution into 260 g of petroleum ether, and use the anti-solvent method to separate the carboxylated polycaprolactone, using ethanol and deionized water (v/v, 1:1). The mixed solution was washed 3 times, 300 g each time, and then washed 4 times with deionized water, 600 g each time, and the obtained product was placed in a vacuum oven and baked at 37 ° C for 24 hours to obtain a carboxyl group-activated Polycaprolactone.

(3) Graft modification

[0065] To a 250 mL three-necked flask was charged 10 g of carboxyl-activated PCL, 16 g of hydrazine, Ν'-carbonyldiimidazole (CDI) and 100 g of dehydrogenated tetrahydrofuran (THF), and dissolved at room temperature. Under nitrogen protection, 12 g of PEG-400 was dissolved in 40 g of dehydrogenated tetrahydrofuran (THF), and added dropwise to a three-necked flask through a constant temperature and constant pressure funnel. After 2 hours, the reaction was carried out for 8 hours at 35 ° C. . After the reaction was completed, the reaction solution was poured into 160 g of petroleum ether, and PCL of grafted PEG-400 was precipitated by anti-solvent method, and filtered to obtain a white solid, which was washed with a mixed solution of ethanol and deionized water (v/v, 1: 1). 4 times, use 300 g each time, then wash 4 times with deionized water, use 600 g each time, put the obtained product into a vacuum oven, and bake at 37 ° C for 24 hours to obtain the graft of grafted PEG-400. Caprolactone.

[0066] The hydrophilic polycaprolactone was dissolved in 1,4-dioxane, formulated into a 20% mass concentration solution, and spin-coated on a spin coater at 2000 rpm to obtain hydrophilicity. Polycaprolactone film. The static contact angle of the polycaprolactone PCL-g-PEG film was measured by a static contact angle of 36°.

Claims

[Claim 1] A method for preparing a hydrophilic polycaprolactone film, comprising the steps of:

(1) Dissolving polycaprolactone in an ether solvent, and then adding an amino alcohol. After the reaction is completed, the reaction solution is poured into an anti-solvent, and then filtered to obtain a solid, that is, hydroxylated polycaprolactone;

(2) dissolving the hydroxylated polycaprolactone in an ether solvent to obtain a hydroxylated polycaprolactone solution; adding succinic anhydride, 4-dimethylaminopyridine, and anhydrous carbonate to the ether solvent to obtain a mixture Then, the hydroxylated polycaprolactone solution is added dropwise to the mixed solution, and the reaction is completed after 0.5 to 2 hours, and then the reaction is completed; after the reaction is completed, the filtrate is filtered, and the diluted acid is added to the filtrate, and the mixture is poured into an anti-solvent. , precipitated solid, that is, carboxylated polycaprolactone;

(3) dissolving carboxylated polycaprolactone, hydrazine, Ν'-carbonyldiimidazole in an ether solvent to obtain a carboxylated polycaprolactone solution; dissolving PEG in an ether solvent under nitrogen protection, and then dropping Adding a carboxylated polycaprolactone solution, adding dropwise after 0.5 to 5 hours, and then reacting; after the reaction is finished, pouring the reaction solution into an anti-solvent to precipitate a white solid, that is, hydrophilic polycaprolactone;

(4) Dissolving hydrophilic polycaprolactone in 1,4-dioxane, preparing a solution of 5%~35% by mass, and spin coating on a spin coater at 1000~8000 rpm. , a hydrophilic polycaprolactone film is obtained.

[Claim 2] The method for producing a hydrophilic polycaprolactone film according to claim 1, wherein the amino alcohol is 2-amino-1-ethanol, 4-amino-1-butanol, and 6 -amino-1-hexanol, 8-aminopicol or ₁₀ -amino-1-nonanol; the terminal hydroxyl polyethylene glycol is PEG100, PEG200, PEG400, PEG600, PEG1000, PEG 1200 ^ PEG 1600 PEG2000 The ether solvent is any one or more mixed solvents of diethyl ether, tetrahydrofuran, and 1,4-dioxane; the anti-solvent is n-pentamidine, n-hexane, n-heptane, Any one or more mixed solvents of n-octane and petroleum ether; the dilute acid is a hydrochloric acid solution or an acetic acid solution; the anhydrous carbonate is potassium carbonate, sodium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate Any of them.

[Claim 3] The method for preparing a hydrophilic polycaprolactone film according to claim 1, wherein: in the step (1), the mass ratio of the amino alcohol to the polycaprolactone is (1 to 10): (1~5); in step (2), succinic anhydride, hydroxylated polycaprolactone, 4-dimethylaminopyridine, anhydrous The mass ratio of carbonate is (1~15): (1~5) : (0.3~3) : (2-10); in step (3), hydroxyl terminated polyethylene glycol, carboxylated polycaprolactone The mass ratio of Ν,Ν'-carbonyldiimidazole is (1.5~15): (0.2~3) : (0.5~5).

[Claim 4] The method for preparing a hydrophilic polycaprolactone film according to claim 1, wherein: in the step (1), the reaction temperature is 40 to 90 ° C, and the reaction time is 1 to 24 hours _; In (2), the reaction temperature is 50 to 90 ° C, and the reaction time is 1 to 12 h; in the step (3), the reaction temperature is 25 to 65 ° (:, the reaction time is 1 to 24 h.

[Claim 5] The method for preparing a hydrophilic polycaprolactone film according to claim 1, wherein the steps (1) to (3) further comprise a purification step, specifically: hydroxylated polycaprolactone Purification, after the reaction is completed, the reaction solution is poured into an anti-solvent, and then filtered to obtain a solid; the solid is first washed with an alcohol solvent 1 to 6 times, and then washed with deionized water for 3 to 5 times; finally at 30 to 45 ° C After drying for 1 to 24 hours, the hydroxylated polycaprolactone is obtained; and the carboxylated polycaprolactone is purified. After the reaction is completed, the filtrate is obtained by filtration, and the diluted acid is added to the filtrate, mixed, poured into an anti-solvent, and precipitated. Solid; the solid is first washed with a mixed solvent of an alcohol solvent and deionized water for 2 to 3 times, then washed with deionized water for 3 to 5 times, and finally baked at 30 ° (: ~ 65 ° C for 1 to 24 hours, That is, the carboxylated polycaprolactone;

Purification of hydrophilic polycaprolactone, after the reaction is completed, the reaction solution is poured into an anti-solvent to precipitate a white solid; the white solid is first washed with a mixed solution of an alcohol solvent and deionized water for 2 to 5 times, and then used. The ionized water is washed 3 to 5 times, and finally baked at 30 ° C to 65 ° C for 1 to 24 hours to obtain hydrophilic polycaprolactone.

[Claim 6] The method for producing a hydrophilic polycaprolactone film according to claim 5, wherein the alcohol solvent is any one or more of ethanol, methanol, and isopropyl alcohol. Mixed solvent.