A combined purification method for glycolide and the obtained glycolide

Abstract

The present invention provides a combined purification method for glycolide and the obtained glycolide. The combined purification method comprises the following steps: (1) melting and filtering crude glycolide to obtain glycolide melt; (2) washing the glycolide melt obtained in step (1) with an organic solvent to obtain glycolide crystals; (3) melting and crystallizing the glycolide crystals obtained in step (2) to obtain refined glycolide. The present invention can reduce the amount of solvent used and purify glycolide with a higher yield and lower energy consumption through a combined purification method of melt filtration, washing and melt crystallization, and the purity of the obtained refined glycolide can reach more than 99.7%.

Description

Technical Field

[0001] The present invention relates to the field of glycolide purification, in particular to a combined glycolide purification method and the obtained glycolide. Background Art

[0002] PGA (polyglycolide) surgical sutures are excellent products among synthetic absorbable sutures. Polyglycolic acid, obtained by ring-opening polymerization of cyclic dimer of glycolic acid (glycolide), is considered an ideal choice for the medical industry due to its excellent degradation performance and unparalleled compatibility with human tissue. Although polyglycolic acid is not the only absorbable polymer material, its excellent performance in human tissue makes this material irreplaceable.

[0003] In order to obtain polyglycolide for sutures, glycolide is usually mixed with an alcohol used as an initiator and a metal compound (such as a tin compound) used as a catalyst and heated to perform ring-opening polymerization. The method for polymerizing glycolide disclosed in U.S. Pat. No. 3,442,871 describes this process in detail. It is generally believed that the glycolide used to prepare PGA must have high chemical purity, because trace impurities such as free glycolic acid, free water, and glycolic acid oligomers in glycolide will have an adverse effect on the polymerization reaction, resulting in a low intrinsic viscosity of the polyglycolide obtained by polymerization.

[0004] At present, the most mature and widely used glycolide synthesis method at home and abroad is mainly the polycondensation-depolymerization method using glycolic acid as raw material. CN105272958A discloses a method for preparing glycolide, which is an example of using polycondensation-depolymerization method to prepare crude glycolide. The crude glycolide obtained by depolymerization reaction usually contains various impurities such as water, glycolic acid, glycolic acid oligomers (molecular weight less than 500g / mol), polyglycolic acid (molecular weight greater than 500g / mol), etc. In addition, carbonaceous intermediates and heavy particles produced by depolymerization side reactions may also enter the condensed crude glycolide with the gas phase. Usually, a purification method is reused or multiple purification methods are combined to fully remove the above-mentioned various impurities.

[0005] The reported purification methods include using various solvents and performing multiple recrystallizations. For example, Example 3 in US Pat. No. 4,727,163A uses ethyl acetate to purify crude glycolide obtained by depolymerization of glycolic acid oligomers. Two recrystallizations can only purify the crude glycolide to 90% purity with a yield of 59.4%.

[0006] There is also a scheme of refining glycolide by coupling recrystallization and alcohol washing in the prior art. For example, patent CN107868075A discloses a method for refining glycolide, wherein crude glycolide is purified by adopting a scheme of cooling recrystallization and filtering and drying after mixed washing with a poor solvent. This method uses alcohols as washing solvents, and the dissolving capacity of alcohols for glycolide is significantly lower than that of good solvents such as ethyl acetate, thereby improving the single-pass refining yield. However, this method has the problem that the impurities adsorbed on the surface of glycolide crystal particles are mainly removed during the mixed washing with a poor solvent, while the impurity crystal nuclei embedded in the crystals are almost unable to be removed, resulting in that the washing effect on impurity purification is not as good as recrystallization, and it is difficult to further purify glycolide after the purity reaches 99.5%. In addition, the amount of solvent used in the purification is still large, and the difficulty of solvent recycling is relatively high.

[0007] Melt crystallization is a method of using the difference in melting points between the components or key components of the separated material to control mass transfer by adjusting the transmission of energy, so that the high melting point component of the mixture is crystallized and precipitated in the molten state to achieve purification. Melt crystallization includes two processes, crystallization and sweating, and does not require an additional solvent. It is especially used in heat-sensitive systems to avoid carbonization, coking and polymerization during the distillation process. However, melt crystallization is usually used under the condition of relatively high raw material purity. If the raw material purity is insufficient, the purity of the mother liquor and the sweating residue is lower, and recycling and reusing will become very difficult, which is not conducive to obtaining a higher comprehensive purification yield. In addition, a single melt crystallization cannot separate impurities with a melting point higher than that of glycolide in crude glycolide, such as polyglycolic acid (molecular weight higher than 500g / mol) and other types of impurities in the form of solid particles in the glycolide melt. There are many types of impurities in the crude glycolide obtained by depolymerization, and the content is high. It is necessary to first use other means to purify glycolide, and then use the melt depolymerization method to prepare high-purity glycolide.

[0008] CN107304196A discloses a method for refining glycolide by coupling vacuum distillation and melt crystallization. The coupling of the two purification methods can effectively separate impurities with a melting point higher than that of glycolide and can reduce the number of distillation times, thereby alleviating phenomena such as carbonization, coking and polymerization. However, these phenomena cannot be avoided, and the vacuum distillation needs to be carried out under high temperature and high vacuum conditions, which has high energy consumption. Summary of the invention

[0009] The technical problem to be solved by the present invention is that the existing crude glycolide purification method has the problems of large solvent usage, high energy consumption and low yield. The existing refined glycolide is usually obtained by filtering and drying the crude glycolide after multiple recrystallization in a good solvent such as ethyl acetate. Since glycolide still has a certain solubility in the good solvent near room temperature, part of the glycolide will inevitably dissolve into the filtrate during filtration, resulting in yield loss, and it is difficult and costly to recover this part of glycolide from the filtrate enriched with acidic impurities. The present invention provides a technical solution for combined purification of glycolide. Impurities with a melting point higher than that of glycolide can be easily removed by melt filtration. The filtered crude glycolide can be purified to a higher purity by washing with an organic solvent, which significantly reduces the number of melt crystallizations. The mother liquor and sweating residue are easy to reuse, and the comprehensive purification yield is high.

[0010] One of the purposes of the present invention is to provide a combined purification method for glycolide, comprising the following steps:

[0011] (1) melting and filtering the crude glycolide to obtain a glycolide melt;

[0012] (2) washing the glycolide melt obtained in step (1) with an organic solvent to obtain glycolide crystals;

[0013] (3) Melt-crystallize the glycolide crystals obtained in step (2) to obtain refined glycolide.

[0014] In the above technical solution, in step (1), the purity of the crude glycolide is 85% to 99.5%.

[0015] In the above technical solution, in step (1), the filter medium is at least one of a woven material, a porous solid, a stacked medium, and a membrane medium. Preferably, the minimum particle size that can be retained by the filter medium is less than or equal to 3 microns.

[0016] In the above technical solution, in step (1), the melting temperature is greater than or equal to 85°C, preferably 85-90°C.

[0017] In the above technical solution, in step (2), the organic solvent is selected from at least one of ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, isobutanol, acetone, ethyl acetate, polyethylene glycol dimethyl ether, and polyethylene glycol monomethyl ether. Preferably, the organic solvent is dehydrated and its water content is less than or equal to 50 ppm.

[0018] In the above technical solution, in step (2), the mass ratio of the glycolide melt to the organic solvent is 0.5-2, preferably 0.5-1.

[0019] In the above technical scheme, in step (2), the glycolide melt is fully contacted with an organic solvent under stirring to form a solid-liquid mixture, and glycolide crystals are obtained by filtering and drying; wherein the contact temperature of the glycolide melt and the organic solvent is preferably less than or equal to 80°C, more preferably 50-70°C; the filtration temperature of the solid-liquid mixture is preferably less than or equal to 50°C, more preferably less than or equal to 20°C.

[0020] In the above technical solution, in step (3), the melt crystallization includes the steps of melting glycolide crystals and then crystallizing them to obtain solid-phase glycolide and sweating the solid-phase glycolide.

[0021] The crystallization is carried out at 70-80°C, preferably at 75°C or higher.

[0022] The sweating is performed at 75-82°C, preferably at 80°C or higher.

[0023] In the above technical solution, the melt crystallization may include the steps of:

[0024] (3-1) heating glycolide crystals to form a melt, cooling the melt in at least one crystallizer, crystallizing the glycolide on the surface of the crystallizer to form solid glycolide, and simultaneously obtaining liquid glycolide, and separating the liquid glycolide;

[0025] (3-2) The solid glycolide in the crystallizer is heated and maintained to sweat, the sweating residual liquid is separated, the temperature is further raised, and the molten glycolide is collected to obtain purified glycolide.

[0026] Furthermore, the melt crystallization may further comprise the steps of:

[0027] (3-3) Recovering the liquid glycolide and the sweat residue, purifying according to step (3) or mixing with fresh crude glycolide and purifying according to steps (1) to (3).

[0028] In the above technical solution, the melt crystallization is carried out in a falling film crystallizer, a static crystallizer or a zone melter.

[0029] The second object of the present invention is to provide refined glycolide obtained by the combined purification method.

[0030] The terminal carboxyl content of the refined glycolide is less than or equal to 10 μmol / g.

[0031] The purity of the refined glycolide can reach above 99.7%.

[0032] The technical solution of the present invention uses a melt filtration, washing and melt crystallization combined purification method to reduce the amount of solvent used and purify glycolide with a higher yield and lower energy consumption. The purity of the obtained refined glycolide can reach more than 99.7%. DETAILED DESCRIPTION

[0033] The present invention is described in detail below in conjunction with specific embodiments. It is necessary to point out that the following embodiments are only used to further illustrate the present invention and cannot be understood as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made to the present invention by those skilled in the art based on the contents of the present invention still fall within the scope of protection of the present invention.

[0034] In addition, the various embodiments of the present invention may be arbitrarily combined as long as they do not violate the concept of the present invention. The technical solutions thus formed belong to part of the original disclosure of this specification and also fall within the protection scope of the present invention.

[0035] The combined purification method of glycolide of the present invention comprises the following steps:

[0036] (1) melting and filtering the crude glycolide to obtain a glycolide melt;

[0037] (2) washing the melt obtained in step (1) with an organic solvent to obtain glycolide crystals;

[0038] (3) Melt-crystallize the glycolide crystals obtained in step (2) to obtain purified glycolide.

[0039] According to a preferred embodiment of the present invention, the combined purification method of glycolide comprises the following steps:

[0040] (i) filtering the crude glycolide product in a molten state to remove solid impurities having a melting point higher than that of glycolide, thereby obtaining a clear glycolide melt G1;

[0041] (ii) the glycolide melt G1 is fully contacted with the organic solvent A under stirring to form a solid-liquid mixture, the solid-liquid mixture is stirred to wash and purify the glycolide to remove acidic impurities, and the washed glycolide crystals G2 are obtained by filtering and drying;

[0042] (iii) heating the glycolide crystals G2 to a sufficient temperature to form a melt, cooling the melt in at least one crystallizer so that the glycolide with a relatively high purity crystallizes on the surface of the crystallizer while the glycolide with a relatively low purity and a high impurity content remains in the liquid phase; and separating the crystallized solid glycolide G3 from the liquid glycolide G4;

[0043] (iv) heating the solid phase glycolide G3 in the crystallizer and maintaining it at a certain temperature to sweat, so that the solid phase glycolide G5 with higher purity is separated from the sweating residue G6; continuing to heat, collecting the molten glycolide to obtain refined glycolide;

[0044] (v) The liquid glycolide G4 and the sweat residue G6 after solid-liquid separation in steps (iii) and (iv) can be regarded as a crude glycolide melt, which can be further purified according to steps (iii) to (iv) to obtain glycolide of the desired purity.

[0045] According to a more preferred embodiment of the present invention, the purity of the glycolide is greater than or equal to 85% and less than 99.5%. The crude glycolide can be obtained by the depolymerization reaction of polyglycolic acid, or it can be glycolide refined by any other refining method but the purity has not reached 99.5%.

[0046] According to a more preferred embodiment of the present invention, the molten state in step (i) is a state in which the crude glycolide is heated to 85°C or above, and the preferred molten state temperature is 85-90°C, for example 85°C, 86°C, 87°C, 88°C, 89°C, 90°C, etc.

[0047] According to a more preferred embodiment of the present invention, the filtration in step (i) is achieved by flowing the molten crude glycolide through a filter medium, and the filter medium includes but is not limited to woven materials, porous solids, stacked media, membrane media, preferably woven materials, and the minimum particle size that can be retained by the filter medium is less than or equal to 3 microns, and the preferred minimum particle size is less than or equal to 1 micron.

[0048] According to a more preferred embodiment of the present invention, in step (ii), the mass ratio of the glycolide melt G1 and the organic solvent A when mixed is greater than or equal to 0.5 and less than or equal to 2, for example, the mass ratio is 0.5, 0.8, 1, 1.2, 1.5, 1.8, 2, etc.; the mass of the melt G1 and the organic solvent A at a lower temperature used for washing does not exceed 2 times the mass of the crystal.

[0049] According to a more preferred embodiment of the present invention, in step (ii), the contact temperature between the glycolide melt G1 and the organic solvent A is less than or equal to 80°C, and the preferred maximum contact temperature is greater than or equal to 50°C and less than or equal to 70°C, for example, the contact temperature can be 50°C, 55°C, 60°C, 65°C, 70°C, 75°C, 80°C, etc. Using hot organic solvent A to stir and wash G1 is conducive to the impurities with lower melting points in G1 to sweat into the solvent, thereby separating from the glycolide composition in the solid phase, and appropriately lowering the temperature of the solid-liquid mixture to less than or equal to 50°C for filtration, so that the glycolide dissolved in the filtrate is as small as possible, and the preferred filtration temperature is less than or equal to 25°C. The impurities previously dissolved in the solvent will be partially precipitated as the temperature decreases, but the particle size is small, and can still enter the filtrate through the filter medium and be separated from the filter cake.

[0050] According to a more preferred embodiment of the present invention, the organic solvent A described in step (ii) is selected from at least one of ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, isobutanol, acetone, ethyl acetate, and polyol ethers (such as polyethylene glycol dimethyl ether, polyethylene glycol monomethyl ether, etc.), and the moisture content after dehydration is less than or equal to 50 ppm.

[0051] According to a more preferred embodiment of the present invention, the crystallizer in step (iii) comprises a falling film crystallizer, a static crystallizer or a zone melter, preferably a falling film crystallizer and a static crystallizer, and more preferably a falling film crystallizer.

[0052] According to a more preferred embodiment of the present invention, the crystallization in step (iii) is carried out at 70-80°C, preferably at 75°C or higher; the sweating in step (iv) is carried out at 75-82°C, preferably at 80°C or higher. For a falling film crystallizer, the crystallizer surface temperature is greater than or equal to 75°C; for a static crystallizer, the temperature at the end of the falling crystallization is greater than or equal to 75°C.

[0053] According to a more preferred embodiment of the present invention, the terminal carboxyl content of the purified glycolide obtained by sweating in step (iv) is less than or equal to 10 μmol / g.

[0054] According to another preferred embodiment of the present invention, the liquid glycolide G4 and the sweat residue G6 after the solid-liquid separation in steps (iii) and (iv) can be recycled to the purification steps (iii) to (iv), or can be mixed with fresh crude glycolide in a certain proportion to achieve application, for example, the mass ratio with fresh crude glycolide is 1 to 4, and the purification steps (i) to (iv) are carried out to obtain the refined glycolide of the required purity.

[0055] The method for determining the free acid concentration of crude glycolide and glycolide in the present invention is as follows:

[0056] The acid-base titration method is used to determine whether the free acid concentration in the crude glycolide is ideal. The specific operation is as follows: the crude glycolide sample is dissolved in about 30 mL of dry dimethyl sulfoxide, and after it is dissolved, a few drops of bromophenol blue indicator solution are dripped into it, and the solution is yellow. It is titrated with a dilute benzyl alcohol solution of sodium hydroxide with a known concentration, and the end point is when the color of the solution changes from yellow to green. The end carboxyl content in glycolide (in μmol) is calculated by calculating the volume of sodium hydroxide solution used when the titration end point is reached, and the free acid concentration of the crude glycolide (in μmol / g) is obtained by dividing it by the mass of the crude glycolide sample.

[0057] The purity determination method of crude glycolide in the present invention is as follows:

[0058] The purity of crude glycolide is determined by gas chromatography (GC). 200 mg of glycolide sample and 40 mg of p-chlorobenzophenone as internal standard substance are dissolved in 10 ml of acetone, and 2 μl of the solution is injected into the gas chromatograph to determine the amount of glycolide; the purity of glycolide is obtained using a standard calibration curve prepared in advance using glycolide standard samples (at least 5 points between 160 and 200 mg) and internal standard substance (40 mg), i.e. p-chlorobenzophenone.

[0059] The purity determination method of refined glycolide in the present invention is as follows:

[0060] The purity of the purified glycolide crystals was analyzed by differential scanning calorimetry (DSC). The instrument model used was TA Discovery. The temperature of glycolide was raised from 65°C to 95°C at a controlled heating rate of 0.5°C / min. The purity of glycolide was analyzed using the software provided by the instrument.

[0061] Unless otherwise specified, the raw materials used in the examples and comparative examples of the present invention are all disclosed in the prior art, for example, they can be directly purchased or prepared according to the preparation methods disclosed in the prior art.

[0062] The present invention will be further described below by way of examples.

[0063] [Example 1]

[0064] Take 300 g of crude glycolide prepared by depolymerization (acid content 470 μmol / g, glycolide purity 88.50%), heat it to 85°C to form a molten state, and filter the melt through a stainless steel woven filter with an average pore size of 3 μm. Then, add it dropwise at a rate of 100 g / min to 300 g of dehydrated isopropanol at a temperature of 25°C. Keep stirring at 180 rpm before and after the addition. After the addition is completed, the solid-liquid mixture is cooled to 25°C, filtered, dried, and the filter cake is collected.

[0065] After the filter cake is heated to 85°C, the melt is conveyed into a static crystallizer. After the surface temperature of the crystallizer is cooled from 82°C at a cooling rate of 1°C / h for 5 hours, the uncrystallized liquid is discharged from the molten crystallizer. The temperature is increased at a rate of 3°C / h to sweat, and the end point temperature of sweating is 80°C. After the molten liquid is completely discharged, the temperature is continued to be increased to melt the crystal layer, discharge it, and collect it. The purified glycolide has a purity of 99.72% and a terminal carboxyl content of 9.0 μmol / g.

[0066] [Example 2]

[0067] Compared with Example 1, the molten filter medium was replaced with a water-based membrane (mixed fiber resin material) with an average pore size of 0.45 μm, and the purified glycolide obtained had a purity of 99.80% and a terminal carboxyl content of 6.5 μmol / g.

[0068] [Example 3]

[0069] Compared with Example 1, isopropanol was replaced by ethanol, and the purity of the obtained refined glycolide was 99.70% and the terminal carboxyl content was 9.6 μmol / g.

[0070] [Example 4]

[0071] Take 300 g of crude glycolide prepared by depolymerization (acid content 470 μmol / g, glycolide purity 88.50%), heat it to 85°C to form a molten state, and filter the melt through a stainless steel woven filter with an average pore size of 3 μm. Then, add it dropwise at a rate of 100 g / min to 300 g of dehydrated isopropanol at a temperature of 25°C. Keep stirring at 180 rpm before and after the addition. After the addition is completed, the solid-liquid mixture is cooled to 25°C, filtered, dried, and the filter cake is collected.

[0072] After the filter cake is heated to 85°C, the melt is transported to the falling film crystallizer. The surface temperature of the crystallizer is maintained at 77°C. After the melt circulates for 2 hours, the uncrystallized liquid is discharged from the crystallizer and sweated at a heating rate of 5°C / h. The sweating end temperature is 81°C. The molten liquid is discharged and the temperature is continued to be increased to melt the crystal layer, discharge it, and collect it. The purified glycolide has a purity of 99.85% and a terminal carboxyl content of 4.8μmol / g.

[0073] [Example 5]

[0074] Compared with Example 4, isopropanol was replaced with n-butanol, and the purity of the obtained refined glycolide was 99.81% and the terminal carboxyl content was 5.5 μmol / g.

[0075] [Example 6]

[0076] Compared with Example 4, 300 g of isopropanol was replaced with 600 g of isopropanol, and the purity of the obtained refined glycolide was 99.87% and the terminal carboxyl content was 4.7 μmol / g.

[0077] [Example 7]

[0078] The uncrystallized liquid in Examples 1 to 3 and the liquid discharged during sweating were collected, a total of 405 grams (acid content 103 μmol / g, glycolide purity 92.50%), heated to 85°C and then conveyed to a falling film crystallizer. The surface temperature of the crystallizer was maintained at 75°C. After the melt circulated for 2 hours, the uncrystallized liquid was discharged from the crystallizer and sweated at a heating rate of 5°C / h. The end temperature of sweating was 80°C. The molten liquid was exhausted and the temperature was continued to be raised to melt the crystal layer, discharge and collect, to obtain refined glycolide with a purity of 99.70% and a terminal carboxyl content of 8.8 μmol / g.

[0079] [Example 8]

[0080] The uncrystallized liquid in Examples 4 to 6 and the liquid discharged during sweating were collected, totaling 340 grams (acid content 124 μmol / g, glycolide purity 91.80%), heated to 85°C and then conveyed to a falling film crystallizer. The surface temperature of the crystallizer was maintained at 75°C. After the melt circulated for 2 hours, the uncrystallized liquid was discharged from the crystallizer and sweated at a heating rate of 5°C / h. The end point temperature of sweating was 80°C. The molten liquid was exhausted and the temperature was continued to be raised to melt the crystal layer, discharge and collect, to obtain refined glycolide with a purity of 99.75% and a terminal carboxyl content of 7.9 μmol / g.

[0081] [Comparative Example 1]

[0082] Compared with Example 1, the stainless steel woven filter was not used for filtration, and the purity of the purified glycolide obtained was 99.52%, and the terminal carboxyl content was 19.0 μmol / g.

[0083] [Comparative Example 2]

[0084] Compared with Example 1, without the isopropanol washing operation, the purity of the obtained refined glycolide was 98.81% and the terminal carboxyl content was 32.0 μmol / g.

[0085] [Comparative Example 3]

[0086] Compared with Example 1, there is no melt crystallization operation, and the filter cake obtained by the first washing-filtration is washed with 300 g of dehydrated isopropanol at a temperature of 25° C. at a stirring rate of 180 rpm. After 1 hour, the solid-liquid mixture is filtered and the filter cake is collected. The filter cake is washed and filtered twice and the solid obtained is vacuum dried at 50° C. for 6 h to obtain refined glycolide with a purity of 99.48% and a terminal carboxyl content of 15.2 μmol / g.

[0087] [Comparative Example 4]

[0088] Take 300g of crude glycolide prepared by depolymerization (acid content 470μmol / g, glycolide purity 88.50%), heat it to 85°C to form a molten state, and convey the melt into a static crystallizer. After the surface temperature of the crystallizer is cooled from 82°C at a cooling rate of 1°C / h for 5 hours, the uncrystallized liquid is discharged from the molten crystallizer; sweating is carried out at a heating rate of 3°C / h, the sweating end temperature is 80°C, the molten liquid is exhausted, and the temperature is continued to be increased to melt and discharge the crystal layer.

[0089] After filtering through a stainless steel woven filter with an average pore size of 3 μm, the melt was added dropwise at a rate of 100 g / min to 300 g of dehydrated isopropanol at 25°C, with stirring maintained at 180 rpm before and after the addition. After the addition was completed, the solid-liquid mixture was cooled to 25°C and filtered, and vacuum dried at 50°C for 6 h to obtain refined glycolide with a purity of 99.12% and a terminal carboxyl content of 30.6 μmol / g.

[0090] [Comparative Example 5]

[0091] Take 300g of crude glycolide prepared by depolymerization (acid content 470μmol / g, glycolide purity 88.50%), heat it to 85°C to form a molten state, and the melt filtered through a stainless steel woven filter with an average pore size of 3 microns is transported to a static crystallizer. After the surface temperature of the crystallizer is cooled from 82°C at a cooling rate of 1°C / h for 5 hours, the uncrystallized liquid is discharged from the molten crystallizer; sweating is carried out at a heating rate of 3°C / h, the sweating end temperature is 80°C, the molten liquid is discharged, and the temperature is continued to be increased to melt the crystal layer and discharge it.

[0092] The melt was added dropwise to 300 g of dehydrated isopropanol at 25°C at a rate of 100 g / min, and the mixture was stirred at 180 rpm before and after the addition. After the addition was completed, the solid-liquid mixture was cooled to 25°C, filtered, dried, and the filter cake was collected. The purified glycolide had a purity of 99.54% and a terminal carboxyl content of 11.8 μmol / g.

Claims

1. A combined purification method for glycolide, comprising the following steps: (1) Melting and filtering the crude glycolide to obtain a glycolide melt; (2) washing the glycolide melt obtained in step (1) with an organic solvent to obtain glycolide crystals; (3) melt-crystallizing the glycolide crystals obtained in step (2) to obtain refined glycolide; In step (1), the melting temperature is 85-90° C.; the filter medium is at least one of a woven material, a porous solid, a stacked medium, and a membrane medium; the minimum particle size that can be retained by the filter medium is less than or equal to 3 μm; and in step (2), the organic solvent is selected from at least one of ethanol, n-propanol, isopropanol, n-butanol, tert-butanol, isobutanol, acetone, ethyl acetate, polyethylene glycol dimethyl ether, and polyethylene glycol monomethyl ether.

2. The combined purification method of glycolide according to claim 1, characterized in that In step (1): The purity of the crude glycolide is 85% to 99.5%.

3. The combined purification method of glycolide according to claim 1, characterized in that In step (2): The mass ratio of glycolide melt to organic solvent is 0.5~2.

4. The combined purification method for glycolide according to claim 3, characterized in that: The moisture content of the organic solvent is less than or equal to 50 ppm; and / or, The mass ratio of glycolide melt to organic solvent is 0.5~1.

5. The combined purification method for glycolide according to claim 1, characterized in that: In step (2), the glycolide melt is fully contacted with an organic solvent under stirring to form a solid-liquid mixture, which is then filtered and dried to obtain glycolide crystals.

6. The combined purification method for glycolide according to claim 5, characterized in that: The contact temperature between the glycolide melt and the organic solvent is less than or equal to 80°C; the filtering temperature of the solid-liquid mixture is less than or equal to 50°C.

7. The combined purification method for glycolide according to claim 6, characterized in that: The contact temperature of the glycolide melt and the organic solvent is 50-70°C; the filtering temperature of the solid-liquid mixture is less than or equal to 25°C.

8. The combined purification method for glycolide according to claim 1, characterized in that: In step (3), the melt crystallization includes the steps of melting glycolide crystals and then crystallizing them to obtain solid-phase glycolide and sweating the solid-phase glycolide.

9. The combined purification method for glycolide according to claim 8, characterized in that: The crystallization is carried out at 70-80°C; and / or, The sweating is carried out at 75-82°C.

10. The combined purification method for glycolide according to claim 9, characterized in that: The crystallization is carried out at a temperature greater than or equal to 75° C.; and / or, The sweating is performed at 80° C. or higher.

11. The combined purification method for glycolide according to claim 8, characterized in that The melt crystallization comprises the steps of: (3-1) heating glycolide crystals to form a melt, cooling the melt in at least one crystallizer, crystallizing glycolide on the surface of the crystallizer to form solid glycolide, and simultaneously obtaining liquid glycolide, and separating the liquid glycolide; (3-2) The solid glycolide in the crystallizer is heated and maintained to sweat, the sweating residual liquid is separated, the temperature is further raised, and the molten glycolide is collected to obtain purified glycolide.

12. The combined purification method for glycolide according to claim 11, characterized in that The melt crystallization comprises the steps of: (3-3) Recovering the liquid glycolide and the sweat residue, purifying according to step (3) or mixing with fresh crude glycolide and purifying according to steps (1) to (3).

13. The combined purification method for glycolide according to any one of claims 5 to 12, characterized in that: The melt crystallization is carried out in a falling film crystallizer, a static crystallizer or a zone melter.