阅读说明：本技术 一种聚乙二醇丙酸酯的分离提纯方法 (Separation and purification method of polyethylene glycol propionate ) 是由 李格丽 邵幼哲 吴传灯 方云辉 林志群 于 2021-10-18 设计创作，主要内容包括：本发明涉及一种聚乙二醇丙酸酯的分离提纯方法,包括步骤将聚乙二醇丙烯酸酯样品用中空纤维膜萃取法、超临界流体萃取法和饱和盐萃取法中的任意一种进行萃取处理,得到萃取液；将所述萃取液进行提纯处理,即得到分离提纯后的聚乙二醇丙酸酯。本发明提供的一种聚乙二醇丙酸酯的分离提纯方法,在简化分离步骤的前提下,解决了现有聚乙二醇丙酸酯的分离提纯过程中的萃取效率低和萃取成本高等问题。(The invention relates to a method for separating and purifying polyethylene glycol propionate, which comprises the steps of carrying out extraction treatment on a polyethylene glycol acrylate sample by any one of a hollow fiber membrane extraction method, a supercritical fluid extraction method and a saturated salt extraction method to obtain an extract liquid; and purifying the extract to obtain the separated and purified polyethylene glycol propionate. The method for separating and purifying the polyethylene glycol propionate solves the problems of low extraction efficiency, high extraction cost and the like in the existing separation and purification process of the polyethylene glycol propionate on the premise of simplifying the separation step.)

1. A method for separating and purifying polyethylene glycol propionate is characterized by comprising the following steps:

extracting a polyethylene glycol acrylate sample by any one of a hollow fiber membrane extraction method, a supercritical fluid extraction method and a saturated salt extraction method to obtain an extract liquid;

purifying the extract to obtain polyethylene glycol propionate after separation and purification;

the molecular formula of the polyethylene glycol propionate is as follows:

wherein R1 and R2 are-H or-CH 3, m is 10-20, and m is an integer.

2. The method of claim 1, wherein the step of purifying the extract solution comprises:

putting the extract into a dialysis bag for dialysis for 2-4d, collecting dialysate, and putting the dialysate into water of 50-70 ℃ for concentration and purification for 1-3d to obtain a concentrated solution, namely the polyethylene glycol propionate after separation and purification.

3. The method for separating and purifying polyethylene glycol propionate as claimed in claim 1, wherein the step of subjecting the polyethylene glycol acrylate sample to extraction treatment by a hollow fiber membrane extraction method comprises the steps of:

placing the hollow fiber membrane cut into 5-10cm into an organic solvent, cleaning with ultrasonic wave for 10-20min, and naturally air drying in a ventilation device;

after one end of the hollow fiber membrane is heat-sealed, injecting the polyethylene glycol acrylate sample and an extractant into the hollow fiber membrane for extraction, and heat-sealing the other end of the hollow fiber membrane;

the extraction time is 2-5h, the extraction temperature is 20-30 ℃, and the extraction liquid is obtained after the extraction is finished.

4. The method of claim 3, wherein the organic solvent comprises at least one of methanol, absolute ethanol and acetone.

5. The method of claim 3, wherein the extractant includes at least one of dichloromethane, dimethyl carbonate, ethylene glycol phenyl ether, and N-methylpyrrolidone.

6. The method for separating and purifying polyethylene glycol propionate as claimed in claim 1, wherein the step of subjecting the polyethylene glycol acrylate sample to extraction treatment by supercritical fluid extraction comprises the steps of:

putting the polyethylene glycol acrylate sample into a separator, and introducing supercritical fluid CO into the separator₂Carrying out extraction treatment;

supercritical fluid CO₂The pressure of the extraction device is controlled at 7000-9000psi, the extraction temperature is 70-90 ℃, the extraction time is 50-100min, and after the extraction is finished, the extracted substances are introduced into a collector to obtain the extraction liquid.

7. The method for separating and purifying polyethylene glycol propionate as claimed in claim 1, wherein the step of extracting the polyethylene glycol acrylate sample by saturated salt extraction comprises the steps of:

preparing a saturated salt solution, adding a polyethylene glycol acrylate sample into the saturated salt solution, and stirring for 5-10min to obtain a mixed solution;

and standing the mixed solution for 10-30min for extraction treatment, and collecting upper-layer oily liquid to obtain the extract liquor.

8. The method of claim 7, wherein the saturated salt solution comprises at least one of a saturated aqueous NaCl solution having a concentration of 5% by mass of NaOH, a saturated aqueous NaCl-ethyl acetate solution, and a saturated aqueous sodium carbonate solution.

9. The method for preparing polyethylene glycol propionate according to claim 2, wherein the dialysis bag comprises one of cellulose membrane and regenerated cellulose membrane dialysis bag, and the MWCO of the dialysis bag is in the range of 100-500D.

10. The method of claim 1, further comprising:

and carrying out qualitative analysis on the separated and purified polyethylene glycol acrylate.

Technical Field

The invention relates to the technical field of polymer separation and purification, in particular to a separation and purification method of polyethylene glycol propionate.

Background

The polyethylene glycol acrylate is a general name of polyethylene glycol with different polymerization degrees and polymer substances with different acrylic acid, has hydrophilic chain segments and hydrophobic chain segments, has better biocompatibility, and has wide application in modification research of various materials.

At present, the separation and purification method of polyethylene glycol acrylate mainly comprises a fractional extraction method, the grade of an extraction section and a washing section of the fractional extraction is more, the steps are complicated, the time consumption is longer, expensive instruments are required, and the method is not beneficial to popularization and application.

Disclosure of Invention

Based on the above, the invention provides a method for separating and purifying polyethylene glycol propionate, which solves the problems of low extraction efficiency, high extraction cost and the like in the existing separation and purification process of polyethylene glycol propionate on the premise of simplifying the separation step.

A method for separating and purifying polyethylene glycol propionate comprises the following steps:

extracting a polyethylene glycol acrylate sample by any one of a hollow fiber membrane extraction method, a supercritical fluid extraction method and a saturated salt extraction method to obtain an extract liquid;

purifying the extract to obtain the separated and purified polyethylene glycol propionate;

the molecular formula of the polyethylene glycol propionate is as follows:

wherein R is₁And R₂is-H or-CH₃M is 10-20, and m is an integer.

Preferably, the step of subjecting the extract to a purification process comprises:

putting the extract into a dialysis bag for dialysis for 2-4d, collecting dialysate, and putting the dialysate into water of 50-70 ℃ for concentration and purification for 1-3d to obtain a concentrated solution, namely the polyethylene glycol propionate after separation and purification.

Preferably, the extraction treatment of the polyethylene glycol acrylate sample by using a hollow fiber membrane extraction method comprises the following steps:

placing the hollow fiber membrane cut into 5-10cm into an organic solvent, cleaning with ultrasonic wave for 10-20min, and naturally air drying in a ventilation device;

after one end of the hollow fiber membrane is heat-sealed, injecting the polyethylene glycol acrylate sample and an extractant into the hollow fiber membrane for extraction, and heat-sealing the other end of the hollow fiber membrane;

the extraction time is 2-5h, the extraction temperature is 20-30 ℃, and the extraction liquid is obtained after the extraction is finished.

Preferably, the organic solvent includes at least one of methanol, absolute ethanol, and acetone.

Preferably, the extractant comprises at least one of dichloromethane, dimethyl carbonate, ethylene glycol phenyl ether and N-methyl pyrrolidone.

Preferably, the extraction treatment of the polyethylene glycol acrylate sample by the supercritical fluid extraction method comprises the following steps:

putting the polyethylene glycol acrylate into a separator, and introducing supercritical fluid CO into the separator₂Carrying out extraction treatment;

supercritical fluid CO₂The pressure of the extraction device is controlled at 7000-9000psi, the extraction temperature is 70-90 ℃, the extraction time is 50-100min, and after the extraction is finished, the extracted substances are introduced into a collector to obtain the extraction liquid.

Preferably, the extraction of the polyethylene glycol acrylate sample by a saturated salt extraction method comprises the following steps:

preparing saturated salt solution, adding polyethylene glycol acrylate into the saturated salt solution, and stirring for 5-10min to obtain mixed solution;

standing the mixed solution for 10-30min for extraction treatment; collecting the upper oily liquid to obtain the extract.

Preferably, the saturated salt solution comprises at least one of a saturated NaCl aqueous solution with 5% by mass of NaOH, a saturated NaCl-ethyl acetate aqueous solution, and a saturated sodium carbonate aqueous solution.

Preferably, the dialysis bag comprises one of a cellulose membrane and a regenerated cellulose membrane dialysis bag, the dialysis bag having a molecular weight cut-off, MWCO, in the range of 100-.

Preferably, the qualitative analysis is performed on the separated and purified polyethylene glycol acrylate.

Compared with the prior art, the invention has the following beneficial effects:

the method adopts one of a hollow fiber membrane extraction method, a supercritical fluid extraction method and a saturated salt extraction method to extract the polyethylene glycol acrylate sample, the steps of extracting the polyethylene glycol acrylate sample by using the method are simple, organic matters and inorganic matters in the polyethylene glycol acrylate sample can be separated by only one-time extraction, multi-section extraction and washing are not needed, the extraction efficiency is high, the extraction cost is low, and the polyethylene glycol acrylate sample separated by extraction is purified subsequently, so that the purpose of separating and purifying the polyethylene glycol acrylate sample is achieved.

Drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of the polyethylene glycol acrylate after separation and purification in example 1;

FIG. 2 is the nuclear magnetic hydrogen spectrum of the polyethylene glycol acrylate after separation and purification in example 2;

FIG. 3 is the nuclear magnetic hydrogen spectrum of the polyethylene glycol acrylate after separation and purification in example 3;

FIG. 4 is a liquid chromatogram of a polyethylene glycol acrylate sample;

FIG. 5 is a liquid chromatogram of polyethylene glycol acrylate after separation and purification.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious 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.

The experimental procedures in the following examples are conventional unless otherwise specified. Test materials, reagents and the like used in the following examples are commercially available unless otherwise specified. In the quantitative tests in the following examples, three replicates were set, and the data are the mean or the mean ± standard deviation of the three replicates.

In addition, "and/or" in the whole text includes three schemes, taking a and/or B as an example, including a technical scheme, and a technical scheme that a and B meet simultaneously; in addition, the technical solutions in the embodiments may be combined with each other, but it is necessary to be able to be realized by those skilled in the art, and when the technical solutions are combined, they are contradictory or unrealistic.

The invention provides a separation and purification method of polyethylene glycol propionate, which comprises the following steps:

extracting a polyethylene glycol acrylate sample by any one of a hollow fiber membrane extraction method, a supercritical fluid extraction method and a saturated salt extraction method to obtain an extract liquid;

purifying the extract to obtain the separated and purified polyethylene glycol propionate;

the molecular formula of the polyethylene glycol propionate is as follows:

wherein R is₁And R₂is-H or-CH₃M is 10-20, and m is an integer.

The method adopts one of a hollow fiber membrane extraction method, a supercritical fluid extraction method and a saturated salt extraction method to extract the polyethylene glycol acrylate sample, the steps of extracting the polyethylene glycol acrylate sample by using the method are simple, organic matters and inorganic matters in the polyethylene glycol acrylate sample can be separated by only one-time extraction, multi-section extraction and washing are not needed, the extraction efficiency is high, the extraction cost is low, and the separated polyethylene glycol acrylate sample is purified subsequently, so that the purpose of separating and purifying the polyethylene glycol acrylate sample is achieved.

The step of purifying the extract comprises:

putting the extract into a dialysis bag for dialysis for 2-4d, collecting dialysate, and concentrating and purifying the dialysate in water of 50-70 deg.C for 1-3d to obtain concentrated solution which is polyethylene glycol propionate obtained after separation and purification.

The extraction liquid is dialyzed and purified by a dialysis method, so that other impurity micromolecule substances in the extraction liquid are completely dialyzed, and the purification precision of the extraction substances is improved.

The polyethylene glycol acrylate sample contains inorganic impurities such as sodium salt and the like and organic impurities such as acrylic acid, methacrylic acid, tartaric acid and the like, the extraction mainly separates the organic matters from the inorganic matters, and the organic layer is collected to be the extraction liquid. The impurities contained in the extract mainly refer to small molecular substances, such as acrylic acid, tartaric acid and the like, and the aim of removing organic impurities is fulfilled by purification.

The purification method in the prior art is commonly a distillation method, a chromatography method and the like, the distillation method needs conditions of high pressure, high temperature and the like, and the high temperature is needed during distillation, so that the safety and environmental protection performance are low; when the chromatography is used, proper eluent, developing agent and the like need to be selected, otherwise, the separation and purification effect is poor, and the selection of the eluent and the developing agent is time-consuming.

In some embodiments, the extraction treatment of the polyethylene glycol acrylate sample by the hollow fiber membrane extraction method comprises the steps of:

placing the hollow fiber membrane cut into 5-10cm into an organic solvent, cleaning with ultrasonic wave for 10-20min, and naturally air drying in a ventilation device;

after one end of the hollow fiber membrane is heat-sealed, injecting the polyethylene glycol acrylate sample and an extractant into the hollow fiber membrane for extraction, and heat-sealing the other end of the hollow fiber membrane;

the extraction time is 2-5h, the extraction temperature is 20-30 ℃, and the extraction liquid is obtained after the extraction is finished.

The hollow fiber extraction method is characterized in that hollow fibers are used as a separation membrane, the hollow fiber membrane has a selective permeability characteristic, the separation purpose is realized by utilizing different migration speeds of organic matters such as polyethylene glycol acrylate and the like and other impurities in the separation membrane, and the separation purpose can be realized only by one-time extraction.

In some embodiments, the organic solvent comprises at least one of methanol, absolute ethanol, and acetone.

In some embodiments, the extractant includes at least one of dichloromethane, dimethyl carbonate, ethylene glycol phenyl ether, and N-methylpyrrolidone.

In some embodiments, supercritical fluid extraction methods include the steps of:

putting a polyethylene glycol acrylate sample into a separator, and introducing supercritical fluid CO into the separator₂Carrying out extraction treatment;

supercritical fluid CO₂Controlling the pressure at 7000-9000psi, the extraction temperature at 70-90 deg.C, the extraction time at 50-100min, introducing the extracted substances into a collector after extraction to obtain the extractive solution, and recovering supercritical CO₂。

The supercritical fluid extraction method is characterized in that a supercritical fluid is used as an extracting agent, a polyethylene glycol acrylate sample is fully contacted with the supercritical fluid, organic matter components such as polyethylene glycol acrylate and the like are selectively dissolved from the polyethylene glycol acrylate sample, and the aim of separating organic matters from inorganic matters at one time is fulfilled through decompression separation.

In some embodiments, the extraction treatment of the polyethylene glycol acrylate sample with a saturated salt extraction method comprises the steps of:

preparing saturated salt solution, adding a polyethylene glycol acrylate sample into the saturated carbonate solution, and stirring for 5-10min to obtain mixed solution;

standing the mixed solution for 10-30min for extraction treatment; collecting the upper oily liquid to obtain the extract.

The saturated salt extraction method is to reduce the hydrophilicity of polyethylene glycol acrylate by using a salting-out effect, and then reduce the solubility of the polyethylene glycol acrylate in water by using a salt solution in a saturated salt solution, so that the polyethylene glycol acrylate is extracted into an organic layer, inorganic matters are remained in an inorganic layer, and the purpose of separating the organic matters from the inorganic matters can be realized only by once extraction.

In some embodiments, the saturated salt solution comprises at least one of a saturated NaCl aqueous solution, a saturated NaCl-ethyl acetate aqueous solution, and a saturated sodium carbonate aqueous solution with a mass concentration of 5% NaOH.

In some embodiments, the dialysis bag comprises one of a cellulose membrane and a regenerated cellulose membrane dialysis bag having a molecular weight cut-off, MWCO, in the range of 100-.

In some embodiments, the qualitative analysis of the separated and purified polyethylene glycol acrylate is performed by the following steps:

performing nuclear magnetic hydrogen spectrum test on the polyethylene glycol acrylate after separation and purification, analyzing the nuclear magnetic spectrogram of the polyethylene glycol acrylate after separation and purification, and analyzing the group-OCH of the polyethylene glycol acrylate₂CH₂- (a) and-CH₃(b) Calculating the molecular weight of the polyethylene glycol acrylate by a formula according to the area of the resonance absorption peak corresponding to the chemical shift;

wherein the formula is:

in the formula: mn is the number average molecular weight of polyethylene glycol acrylate, Aa is the integral area of a proton peak at a, Ab is the integral area of a proton peak at b, and 44 is-OCH₂CH₂-the molar mass of the repeating unit of (a).

The invention adopts the nuclear magnetic hydrogen spectrometry to separate and purify the polyethylene glycol acrylate for qualitative analysis, and calculates the molecular weight of the polyethylene glycol acrylate through the peak area, so that the obtained molecular weight is real and reliable.

Example 1

Cutting a 5cm hollow fiber membrane into pieces, placing in methanol, performing ultrasonic cleaning for 10min, and naturally air drying in a fume hood;

after one end of the hollow fiber membrane is heat-sealed, injecting a polyethylene glycol acrylate sample and dimethyl carbonate into the hollow fiber membrane for extraction, and heat-sealing the other end of the hollow fiber membrane;

the extraction temperature is 30 ℃, the extraction time is 3h, and after the extraction is finished, the extraction liquid is obtained.

Putting the extract into a cellulose membrane dialysis bag with the molecular weight cut-off (MWCO) of 100D for dialysis for 2D, collecting dialysate, putting the dialysate into water at 60 ℃ for concentration and purification for 2D to obtain a concentrated solution, namely the polyethylene glycol propionate after separation and purification;

performing nuclear magnetic hydrogen spectrum test on the separated and purified polyethylene glycol propionate, wherein the nuclear magnetic hydrogen spectrum of the separated and purified polyethylene glycol acrylate is shown in figure 1.

From FIG. 1, — OCH₂CH₂The area of the resonance absorption peak corresponding to the chemical shift of (a) is about 20 and the area of the resonance absorption peak is about-CH₃(b) The area of the resonance absorption peak corresponding to the chemical shift is about 6, and the molecular weight is calculated according to a formula to be 110.

Example 2

Putting a polyethylene glycol acrylate sample into a separator, and introducing supercritical fluid CO into the separator₂Carrying out extraction treatment;

supercritical fluid CO by adjusting flow restrictor in separator₂Pressure control at 7000 psi;

extracting at 70 deg.C for 50min, introducing the extracted substances into a collector to obtain extractive solution, and recovering supercritical CO₂。

Putting the extract into a regenerated cellulose membrane dialysis bag with the molecular weight cut-off (MWCO) of 300D for dialysis for 3D, collecting dialysate, putting the dialysate into water at 50 ℃ for concentration and purification for 2D to obtain a concentrated solution, namely polyethylene glycol propionate obtained after separation and purification;

performing nuclear magnetic hydrogen spectrum test on the separated and purified polyethylene glycol propionate, wherein the nuclear magnetic hydrogen spectrum of the separated and purified polyethylene glycol acrylate is shown in fig. 2.

As can be seen from FIG. 2, -OCH₂CH₂The area of the resonance absorption peak corresponding to the chemical shift of (a) is about 60, -CH₃(b) The area of the resonance absorption peak corresponding to the chemical shift is about 3, and the molecular weight is 660 according to the formula.

Example 3

Preparing 200mL of 5% NaOH saturated NaCl aqueous solution, adding a polyethylene glycol acrylate sample into a saturated carbonate solution, and stirring for 10min to obtain a mixed solution;

standing the mixed solution for 20min for extraction treatment, and collecting upper oily liquid to obtain extract.

Putting the extract into a dialysis bag made of a regenerated cellulose membrane with the MWCO of 500D for dialysis for 3D, collecting dialysate, putting the dialysate into water at 70 ℃ for concentration and purification for 3D to obtain a concentrated solution, namely polyethylene glycol propionate obtained after separation and purification;

performing nuclear magnetic hydrogen spectrum test on the separated and purified polyethylene glycol propionate, wherein the nuclear magnetic hydrogen spectrum of the separated and purified polyethylene glycol propionate is shown in fig. 3.

From FIG. 3, it can be seen that-OCH₂CH₂(a) the area of the resonance absorption peak corresponding to the chemical shift is about 60, and-CH₃(b) The area of the resonance absorption peak corresponding to the chemical shift is about 4, and the molecular weight is about 500 according to the formula calculation.

Liquid chromatogram before and after purification of polyethylene glycol propionate sample are shown in FIG. 4 and FIG. 5, respectively.

As can be seen from fig. 4 and 5, after separation and purification, the liquid chromatogram of the separated and purified polyethylene glycol propionate sample has only two chromatographic peaks, while six chromatographic peaks before purification, and more impurity peaks before separation and purification, and the impurity peaks after separation and purification disappear, so that the separation and purification purposes are achieved.

The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.