阅读说明：本技术 一种聚酯类产品的纯化方法和生产设备 (Purification method and production equipment for polyester products ) 是由 于崆峒 蒋朝军 荆志宇 杜保国 于 2020-12-29 设计创作，主要内容包括：本发明涉及一种聚酯类产品的纯化方法和生产设备,该方法包括：步骤A,将聚酯类产品溶于第一溶剂,随后在搅拌条件下将第一沉淀剂加入,直至析出聚酯沉淀,得到聚酯混悬液,分离所述聚酯混悬液,收集得到固体分离物；步骤B,将所述固体分离物重新溶解于第一溶剂中,形成预定浓度的聚酯溶液,将所述聚酯溶液通过雾化器喷入第一沉淀剂中,形成的奶油状固体漂浮在所述第一沉淀剂的表面,随后进行固液分离,采用新鲜的第一沉淀剂进行清洗并干燥,得到纯化后的聚酯类产品。本方法适合于制备具有高纯度、极低寡聚体及单体含量的聚酯产品,并且可以以工业化规模进行生产,单批批量可达1～10kg。(The invention relates to a purification method and production equipment of polyester products, wherein the method comprises the following steps: step A, dissolving a polyester product in a first solvent, then adding a first precipitator under the stirring condition until a polyester precipitate is separated out to obtain a polyester suspension, separating the polyester suspension, and collecting to obtain a solid isolate; and B, re-dissolving the solid isolate in a first solvent to form a polyester solution with a preset concentration, spraying the polyester solution into a first precipitator through an atomizer, floating the formed creamy solid on the surface of the first precipitator, then performing solid-liquid separation, and cleaning and drying by using a fresh first precipitator to obtain the purified polyester product. The method is suitable for preparing polyester products with high purity and extremely low oligomer and monomer contents, and can be used for industrial scale production, and the single batch can reach 1-10 kg.)

1. A method for purifying a polyester product, comprising:

step A, dissolving a polyester product in a first solvent, then adding a first precipitator under the stirring condition until a polyester precipitate is separated out to obtain a polyester suspension, separating the polyester suspension, and collecting to obtain a solid isolate;

and B, re-dissolving the solid isolate in a first solvent to form a polyester solution with a preset concentration, spraying the polyester solution into a first precipitator through an atomizer, floating the formed creamy solid on the surface of the first precipitator, then performing solid-liquid separation, and cleaning and drying by using a fresh first precipitator to obtain the purified polyester product.

2. Purification process according to claim 1, characterized in that the first solvent is selected from one or more mixtures of acetone, dichloromethane, chloroform, preferably the first solvent is selected from acetone.

3. Purification process according to claim 1, characterized in that the first precipitating agent is selected from one or more of methanol, ethanol, water, preferably the first precipitating agent is selected from water.

4. The purification process according to claim 1, wherein in step a, the ratio of the first solvent to the first precipitant is 100: 40-100: 60(v/v), preferably the ratio of the first solvent to the first precipitant is 100: 50 (v/v).

5. The purification method according to claim 1, wherein in the step B, the concentration of the redissolved polyester solution is 5-50% (w/v), preferably, the concentration of the polyester solution is 15-30% (w/v).

6. The purification process according to claim 1, wherein in step B, the ratio of the first precipitant to the first solvent is greater than 100: 1 (v/v).

7. The polyester-based product obtained by the purification method according to any one of claims 1 to 6, wherein the oligomer content (Mw < 2000) is 5% or less, the monomer content (lactide, glycolide, lactic acid, glycolic acid) is 0.05% or less, the solvent content (acetone) is 0.1% or less, and the solvent content (water) is 0.5% or less.

8. A production facility for implementing the purification method of claim 1, characterized in that: the polyester production line comprises a first precipitator storage tank, a first solution storage tank, a first separator, a second solution storage tank, an atomizer, a second precipitator storage tank, a second separator and a dryer which are sequentially connected, wherein the first solution storage tank is used for storing polyester product solution, the first precipitator storage tank is used for storing first precipitator, a mixer is arranged in the first solution storage tank, the first precipitator in the first precipitator storage tank is transferred into the first solution storage tank at a constant speed and is continuously stirred to be uniformly mixed to form polyester suspension, the formed polyester suspension is introduced into the first separator to be subjected to solid-liquid separation, solid separation sediment is collected and re-dissolved and is transferred into the second solution storage tank, the polyester solution in the second solution storage tank is sprayed into the second precipitator storage tank through the atomizer, and formed creamy solid floats on the liquid surface of the second precipitator storage tank, and then carrying out solid-liquid separation by using a second separator, washing in the second separator, and finally transferring to a dryer for drying.

9. The production facility according to claim 8, wherein the mixer is an overhead paddle.

10. The production facility of claim 8, wherein the first separator is selected from a centrifuge or a cone separator.

11. The production plant according to claim 8, wherein the first separator is selected from the group consisting of conical separators.

12. The production apparatus according to claim 8, wherein the atomizer is selected from a two-fluid nozzle.

13. The production facility of claim 8 wherein the second precipitant storage tank comprises three functional zones, an upper zone for precipitation, a middle zone for screen retention, and a lower zone for precipitant exchange.

14. The production facility according to claim 13, wherein the second precipitant tank has a height to diameter ratio of 1:1 to 1:3, preferably 1: 2.

15. The production facility according to claim 13, wherein the aperture of the middle interception screen of the second precipitant tank is 75 to 150 μm, preferably 125 to 150 μm.

16. The manufacturing apparatus of claim 13, wherein the second precipitant tank has a second precipitant inlet and outlet at a lower side thereof, wherein the second precipitant inlet is disposed at one side of the lower portion of the second precipitant tank body at an angle of 45 ° obliquely upward, and the second precipitant outlet is disposed at the other side of the bottom of the second precipitant tank body at an angle of 0 ° horizontally.

17. The production plant according to claim 8, characterized in that the second separator is selected from a vibrating screen.

18. The production facility according to claim 8, wherein the drying means is selected from the group consisting of pneumatic drying, vacuum drying, freeze drying, preferably wherein the drying means is selected from the group consisting of pneumatic drying.

Technical Field

The invention relates to the field of biocompatible biodegradable polymers, in particular to a purification method and production equipment for polyester products.

Background

Biodegradable polyesters have long been widely used for controlled drug delivery, and they have the advantage that they do not require surgical removal after the sustained release is complete, and can be excluded from the body by direct enzymatic or chemical degradation into small molecules. Polylactic (PLA) and polylactic glycolic (PLGA) families have shown desirable biocompatible properties and are therefore widely accepted as pharmaceutical components and particularly for use in sustained release formulations.

The drug encapsulated in the polylactic acid particles is released by the diffusion action of the aqueous environment or the degradation of the polymer. The properties of polyester-based products significantly affect the in vitro and in vivo drug release behavior of microspheres made from polyester. The molecular weight is the first thing to come, and the molecular weight and distribution of the polyester influence the biodegradation rate. For a diffusion mechanism of active agent release, the polymer should remain intact until all of the active agent is released from the microsphere, and then degrade.

The synthetic method of the polyester is well known in the art, and can be prepared by the polycondensation of lactic acid, or lactic acid and glycolic acid, or by the ring-opening polymerization of lactide, or lactide and glycolide. In any synthesis route, by-products such as unconverted monomers and oligomers must be present.

The presence of monomers and oligomers in polyesters is a serious problem, monomers are extremely unstable, and rapidly decompose into equivalent acids in a high humidity environment, which in turn catalyze the degradation of polyester products, and consequently affect the processing stability and storage stability of the polyester products. Oligomers refer to low molecular weight polymers, generally defined as polymers with a molecular weight below 2000, the presence of which makes polyesters prone to release the active agent in a faster manner (Asano et al, Biomaterials,1989, vol.10: 569, it causes sudden release of the drug, which brings risk to clinical safety. When the active agent needs to be delivered at a smooth concentration over a longer period of time, the amount of monomers and oligomers in the polymer should be reduced. For polyester synthesis reaction, the monomer residual amount is usually 1-3%, the oligomer residual amount can reach 10-20%, and the oligomer distribution and the monomer residual amount in different batches have certain difference. It is this difference that causes instability of polyester-based products, resulting in difficulties in quality reproduction and process reproduction of finished products of formulations obtained using polyester-based products.

Purification processes for separating residual monomers from crude polyester products are known, for example, by dissolving polyester products in an organic solvent, selecting a poor solvent which dissolves the monomers but does not dissolve the polyester, and removing the unreacted monomers by causing precipitation of the polymer by adding an excess of the poor solvent.

However, the prior art still has the problems of complicated process steps and difficult industrialization in the laboratory stage of residual monomer removal, a large amount of organic solvent is usually introduced into the purification process, so that the later-stage solvent removal is difficult, some solvents even adopt strong polar solvent ethanol and the like, the solvents do not completely dissolve the polymer, at least the polymer can be swelled, so that obvious polyester particles and solvent interfaces cannot be formed, and the formed polyester precipitates are aggregated together due to the polarity problem, so that the separation and drying of the later-stage product are difficult.

Another important problem is that current polyester purification processes focus primarily on catalyst residues, monomer residues and solvent residues, and do not effectively control oligomer residue levels, which remains uncertain as to the quality and processing stability of the polyester, and batch-to-batch uniformity.

Therefore, the prior art lacks a technical means capable of effectively removing monomers and oligomers at the same time, so that the technical means can be maintained at an extremely low level to ensure the stability and batch-to-batch uniformity of polyester products; the prior art lacks a method and apparatus capable of performing polyester purification in kilogram batches.

Disclosure of Invention

An object of the embodiments of the present invention is to provide a method and an apparatus for purifying polyester-based products, which can solve the problems of the related art that monomers and oligomers in the polyester-based products can be simultaneously maintained at an extremely low level, and that the purification of polyesters can be performed in a kilogram-scale batch. The method provided by the embodiment of the invention can purify the polyester in kilogram-grade batches, simultaneously reduces monomers and oligomers in the polyester product to an extremely low level, obtains the high-purity polyester with narrower molecular weight distribution, and solves the problems of instability and poor batch processing reproducibility of the polyester product in the placing process.

According to a first aspect of the present invention, there is provided a method for purifying a polyester-based product, comprising:

step A, dissolving a polyester product in a first solvent, then adding a first precipitator under the stirring condition until a polyester precipitate is separated out to obtain a polyester suspension, separating the polyester suspension, and collecting to obtain a solid isolate;

and B, re-dissolving the solid isolate in a first solvent to form a polyester solution with a preset concentration, spraying the polyester solution into a first precipitator through an atomizer, floating the formed creamy solid on the surface of the first precipitator, then performing solid-liquid separation, and cleaning and drying by using a fresh first precipitator to obtain the purified polyester product.

Further, the first solvent is selected from one or more of acetone, dichloromethane and chloroform, preferably, the first solvent is selected from acetone.

Further, the first precipitator is selected from one or more of methanol, ethanol and water, and preferably, the first precipitator is selected from water.

Further, in the step a, the ratio of the first solvent to the first precipitant is 100: 40-100: 60(v/v), preferably the ratio of the first solvent to the first precipitant is 100: 50 (v/v).

Further, in the step B, the concentration of the redissolved polyester solution is 5-50% (w/v), preferably, the concentration of the polyester solution is 15-30% (w/v).

Further, in the step B, the ratio of the first precipitating agent to the first solvent is greater than 100: 1 (v/v).

The polyester-based product obtained by the above purification method has an oligomer content (Mw < 2000) of 5% or less, a monomer content (lactide, glycolide, lactic acid, glycolic acid) of 0.05% or less, a solvent content (acetone) of 0.1% or less, and a solvent content (water) of 0.5% or less.

According to a second aspect of the embodiments of the present invention, there is provided a production apparatus for the purification method according to the first aspect, comprising a first precipitant storage tank, a first solution storage tank, a first separator, a second solution storage tank, an atomizer, a second precipitant storage tank, a second separator, and a dryer, which are connected in sequence, wherein the first solution storage tank is used for storing a polyester-based product solution, the first precipitant storage tank is used for storing a first precipitant, a mixer is installed in the first solution storage tank, the first precipitant in the first precipitant storage tank is transferred to the first solution storage tank at a constant speed and is continuously stirred to be uniformly mixed to form a polyester suspension, the formed polyester suspension is introduced into the first separator to perform solid-liquid separation, the collected solid isolate precipitate is re-dissolved and then transferred to the second solution storage tank, the polyester solution in the second solution storage tank is sprayed into the second precipitant storage tank through the atomizer, the formed cream-like solid floats on the liquid surface of the second precipitator storage tank, and then is subjected to solid-liquid separation by using a second separator, is washed in the second separator and is finally transferred to a dryer for drying.

Further, the mixer adopts an overhead stirring paddle.

Further, the first separator is selected from a centrifuge or a cone separator.

Further, the first separator is selected from a conical separator.

Further, the atomizer is selected from a two-fluid nozzle.

Furthermore, the second precipitator storage tank comprises three functional areas, wherein the upper part is a precipitation area, the middle part is a screen interception area, and the lower part is a precipitator replacement area.

Further, the height-diameter ratio of the second precipitator storage tank is 1: 1-1: 3, preferably 1: 2.

Furthermore, the aperture of the middle interception screen of the second precipitator storage tank is 75-150 μm, preferably 125-150 μm.

Further, a second precipitator inlet and a second precipitator outlet are arranged on the lower side face of the second precipitator storage tank, wherein the second precipitator inlet is arranged on one side face of the middle lower portion of the second precipitator storage tank body at an angle of 45 degrees upwards in an inclined mode, and the second precipitator outlet is arranged on the other side face of the bottom of the second precipitator storage tank body at an angle of 0 degree horizontally.

Further, the second separator is selected from a shaker screen.

Further, the drying manner is selected from air flow drying, vacuum drying and freeze drying, and preferably, the drying manner is selected from air flow drying.

The technical scheme provided by the embodiment of the application can have the following beneficial effects:

as can be seen from the above examples, oligomers can be quantitatively removed by step A, reducing the initial burst of the formulation caused by the ultra low molecular weight polymer. The polyester after removal of the oligomers is redissolved in a first solvent and subsequently mixed with a large amount of a first precipitant by means of an atomizer. The polyester solution can be sprayed into a large amount of first precipitating agents at a constant speed through the two-fluid nozzle, the breaking force of the gas is utilized to realize the full breaking of liquid drops and the separation of polyester particles at the interface of the gas, the polyester solution and the precipitating agents, and the polyester product can be broken into tiny particles through the step B, so that the drying of the later-stage product is facilitated. Thereby, the residual monomer and the residual solvent can be effectively removed through the step B. The technical scheme provided by the embodiment of the application has obvious effect of removing oligomers, monomers and residual solvents, wherein the content of oligomers with the daltons of less than 2000 can be reduced to less than 2%, and the burst effect of the drug-loaded particles is greatly reduced; wherein the monomer residue is as low as 0.05% or less; the residual solvent amount used for purification is lower than 0.05 percent; the water content is less than 0.5%.

The invention provides a polyester with extremely high quality, more uniform molecular weight distribution, 1.3-1.5 molecular weight span, increased preparation stability and safety in clinical use.

The method for purifying the polyester has the advantages of low cost, high efficiency and good quality.

It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the application.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the present application and together with the description, serve to explain the principles of the application.

FIG. 1 is a schematic diagram of a polyester product purification system shown according to an exemplary embodiment;

FIG. 2 is a size exclusion chromatogram of a polyester product prior to purification, shown in accordance with an exemplary embodiment 1;

FIG. 3 is a size exclusion chromatogram of a purified polyester product shown according to an exemplary embodiment 1;

legend: 1-a first solution storage tank; 2-a first overhead stirring paddle; 3-feeding lining pipe; 4-a first precipitant storage tank; 5-a first fluid pump; 6-a second fluid pump; 7-conical separator feed inlet; 8-a conical separator; 9-conical separator discharge port; 10-a conical separator clear liquid outlet; 11-a third fluid pump; 12-a second solution storage tank; 13-a second overhead paddle; 14-feed liquid transfer tube; 15-two fluid nozzle feed liquid inlet; 16-two fluid nozzle gas inlet; 17-a two-fluid nozzle; 18-a second precipitant storage tank; 19-a precipitation zone; 20-screen entrapment zone; 21-precipitant exchange zone; 22-a precipitant bottom outlet; 23-precipitant side liquid inlet; 24-polyester precipitation slag discharge port; 25-liquid inlet at the top of the precipitator; 26-a fourth fluid pump; 27-a vibrating screen; 28-dryer.

Detailed Description

Reference will now be made in detail to the exemplary embodiments, examples of which are illustrated in the accompanying drawings. When the following description refers to the accompanying drawings, like numbers in different drawings represent the same or similar elements unless otherwise indicated. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present application. Rather, they are merely examples of apparatus and methods consistent with certain aspects of the present application, as detailed in the appended claims.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used in this application and the appended claims, the singular forms "a", "an", and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It should also be understood that the term "and/or" as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items.

Example 1:

this embodiment provides a method for purifying polyester products, comprising:

step A, dissolving a polyester product in a first solvent, then adding a first precipitator under the stirring condition until a polyester precipitate is separated out to obtain a polyester suspension, separating the polyester suspension, and collecting to obtain a solid isolate; oligomers can be quantitatively removed by step a, reducing the initial burst of the formulation caused by the ultra low molecular weight polymer.

The oligomer described in the examples of the present invention refers to a polyester having a molecular weight of about 2000 or less, and this partial molecular weight polyester may cause a serious burst.

In the embodiment of the invention, the first solvent is one or more selected from acetone, dichloromethane and chloroform; the solvent is suitably selected according to the type of polyester and the intrinsic viscosity of the polyester in the solvent. Acetone has been found to be particularly suitable for the first solvent.

In the embodiment of the present invention, the first precipitating agent is selected from one or more of methanol, ethanol and water, and water is particularly suitable for the first precipitating agent according to the special properties of the polyester in the first solvent and the first precipitating agent. The water is nontoxic and low-cost liquid, and is preferable in environment and use effect.

Further, in the embodiment of the present invention, in the step a, the ratio of the first solvent to the first precipitant is 100: 40-100: 60(v/v), preferably the ratio of the first solvent to the first precipitant is 100: 50 (v/v).

Through the step a, the technical effect achieved by the embodiment of the present invention is that the oligomer content in the polyester product can be controlled below 5%, and further, the oligomer content in the polyester product can be controlled below 2%.

And B, re-dissolving the solid isolate in a first solvent to form a polyester solution with a preset concentration, spraying the polyester solution into a first precipitator through an atomizer, floating the formed creamy solid on the surface of the first precipitator, then performing solid-liquid separation, washing and drying by using a fresh first precipitator to obtain the purified polyester product, wherein the method can also obtain the polyester with reproducible high quality on an industrial scale.

According to an embodiment of the present invention, the polyester after removing oligomers is redissolved in a first solvent and then mixed with a large amount of a first precipitant through an atomizer. The polyester solution can be sprayed into a large amount of first precipitating agents at a constant speed through the two-fluid nozzle, the breaking force of the gas is utilized to realize the full breaking of liquid drops and the separation of polyester particles at the interface of the gas, the polyester solution and the precipitating agents, and the polyester product can be broken into tiny particles through the step, so that the drying of the product at the later stage is facilitated. Thereby, the residual monomer and the residual solvent can be effectively removed through the step B.

In order to improve the later-stage drying effect of the polyester product and improve the particle fineness of the powder, in the step B, the concentration of the redissolved polyester solution is 5-50% (w/v), and preferably, the concentration of the polyester solution is 15-30% (w/v).

According to the steps, when the ratio of the first precipitating agent to the first solvent is more than 100: 1(v/v), the levels of residual monomer and residual solvent can be significantly reduced. The residual monomers include lactide and glycolide, and the residual solvents include but are not limited to acetone, dichloromethane, chloroform, methanol, ethanol, and water.

The content of lactide in the polyester product prepared by the method can be reduced to be below 0.1 percent, and further the content of lactide can be reduced to be below 0.05 percent.

The content of glycolide in the polyester product prepared by the method can be reduced to be below 0.1%, and further the content of glycolide can be reduced to be below 0.05%.

The content of lactic acid in the polyester product prepared by the method can be reduced to below 0.05 percent.

The content of glycolic acid in the polyester products prepared by the method can be reduced to below 0.05 percent.

The content of acetone in the polyester product prepared by the method can be reduced to be below 0.1 percent, and further the content of acetone can be reduced to be below 0.05 percent.

The water content of the polyester product prepared by the method can be reduced to be below 0.5 percent, and further, the water content can be reduced to be below 0.1 percent.

The weight average molecular weight of the polyester product prepared by the above method is 10,000-100,000, and more preferably, the weight average molecular weight is 10,000-30,000.

The polydispersity of the polyester product prepared by the above method is between 1.3 and 1.5.

The polyester products after the removal of oligomers, residual monomers and residual solvents as described above can be controlled to form microparticles suitable for injection into a patient in need thereof, and thus, embodiments of the present invention also relate to pharmaceutically acceptable formulations of the polyester products purified by embodiments of the present invention, although the scope of embodiments of the present invention is limited only by the claims.

Example 2:

as shown in fig. 1, an embodiment of the present invention further provides a production apparatus for the purification method according to embodiment 1, which includes a first precipitant storage tank 4, a first solution storage tank 1, a first separator, a second solution storage tank 12, an atomizer, a second precipitant storage tank 18, a second separator, and a dryer, which are connected in sequence, where the first solution storage tank 1 is used to store a polyester-based product solution, the first precipitant storage tank 4 is used to store a first precipitant, a mixer is installed in the first solution storage tank 1, the first precipitant in the first precipitant storage tank 4 is transferred to the first solution storage tank 1 at a constant speed and is continuously stirred to be uniformly mixed, a formed polyester suspension is formed, the formed polyester suspension is introduced into the first separator to perform solid-liquid separation, a solid precipitate is collected and redissolved and then transferred to the second solution storage tank 12, the polyester solution in the second solution storage tank 12 is sprayed into the second precipitator storage tank 18 through an atomizer, the formed creamy solid floats on the liquid surface of the second precipitator storage tank 18, and then solid-liquid separation is carried out by using a second separator, and cleaning is carried out in the second separator, and finally, the second separator is transferred to a dryer for drying.

Specifically, a first precipitator storage tank 4 is communicated with a feeding lining pipe 3 on a first solution storage tank 1 through a pipeline, a first fluid pump 5 can be arranged in the pipeline to drive the liquid to flow, a first overhead stirring paddle 2 is arranged in the first solution storage tank 1 and is used for stirring and mixing the liquid in the first solution storage tank 1, the first solution storage tank 1 is communicated with a cone-shaped separator feeding hole 7 through a pipeline and a tank body, polyester suspension is fed into the cone-shaped separator 8 for solid-liquid separation, a second fluid pump 6 can be arranged in the pipeline to drive the liquid to flow, a cone-shaped separator clear liquid outlet 10 is used for pumping supernatant through a third fluid pump 11, separated syrup-like polyester precipitate is enriched through a cone-shaped separator discharging hole 9 and then transferred to a second solution storage tank 12, a second overhead stirring paddle 13 is arranged in the second solution storage tank 12 and is used for stirring and mixing the liquid in the second solution storage tank 12, the second solution storage tank 12 is provided with a feed liquid transfer pipe 14, and is communicated with the atomizer through the feed liquid transfer pipe 14, in this example, the atomizer is selected from a two-fluid nozzle, a feed liquid inlet 15 of the two-fluid nozzle 17 is communicated, compressed air is introduced into a gas inlet 16 of the two-fluid nozzle 17, the two-fluid nozzle 17 is placed under the liquid level of the second precipitator, the second precipitator storage tank 18 is further provided with a 22, a precipitator side liquid inlet 23, a polyester precipitation slag discharge port 24 and a precipitator top liquid inlet 25, the polyester precipitation slag discharge port 24 is communicated with an oscillating screen 27 through a pipeline, and a fourth fluid pump 26 can be installed in the pipeline and is used for discharging the polyester precipitation into the oscillating screen 27, concentrating the polyester precipitation in the oscillating screen 27, and finally drying the polyester precipitation in a dryer 28.

In the oligomer removing process, the mixer is preferably selected to be an overhead paddle 2 for solid-liquid mixing according to the specific state of the product, and if the mixer is selected to be a bottom paddle, the yield of the product is further lost, and the polyester precipitates as syrup-like solids and is easily attached to the paddle.

The first separator for separating the polyester suspension is preferably a centrifuge or a cone separator, particularly preferably a cone separator, which allows uninterrupted processing of the feed solution, separation of the supernatant and redissolving of the polyester precipitate with the first solvent.

The solvent flash point of the organic solvent is low, and the cone-shaped separator is preferably used for separating the solid polyester suspension, wherein the suspension is introduced into the inlet of the separator in a tangential flow mode, the fluid changes from linear motion into circular motion, the precipitate descends along the wall of the separator under the action of centrifugal force and enters the second solution storage tank 12 after being transferred, the rotating supernatant fluid flows to the center in the separator, and the supernatant fluid flows upwards to form vortex and flows out of the separator through the outlet of the separator.

The ratio of the first precipitant to the first solvent is required to be as large as possible for more sufficient removal of the residual monomer and the residual solvent, so that the volume of the precipitation tank must be large and there are problems in the later separation of the polyester suspension.

The second precipitant tank 18 used in the present embodiment to implement the above precipitation process needs to have a special configuration according to the specific ratio of the first precipitant to the first solvent. The second precipitant reservoir 18 includes three functional zones: the upper part is a settling zone 19, the middle part is a screen trapping zone 20, and the lower part is a precipitant changing zone 21. The process of forming the polyester solution into particles mainly occurs in the upper precipitation zone 19, and the precipitated polyester particles finally float on the surface of the second precipitator after descending for a period under the action of the initial speed; the middle part of the second precipitator storage tank 18 is a screen entrapment area 20, and a section of screen with a certain aperture is inserted, so that descending polyester particles can be effectively entrapped, the polyester particles and a large amount of precipitants are in a separation state, and only a small amount of precipitants are kept in contact; the lower part of the screen is a precipitant replacement area 21, and in order to meet the requirement of low residual monomers and residual solvents, the second precipitant needs to be continuously replaced, so that the second precipitant extracting the residual monomers and the residual solvents is replaced in time, and the polyester product is prevented from being polluted.

According to the embodiment of the invention, the height-diameter ratio of the second precipitator tank 18 is 1: 1-1: 3, preferably 1: 2. A liquid inlet is formed in the top of the upper settling zone 19 of the second precipitator storage tank 18, and the direction of the liquid inlet at the top is vertical to the middle intercepting screen mesh and can cover the surface of the solution; the side surface of the top of the upper settling zone 19 is additionally provided with a liquid inlet, and the direction of the liquid inlet is parallel to the middle interception screen. The aperture of the middle interception screen of the second precipitator storage tank 18 is 75-150 μm, preferably 125-150 μm. And a precipitating agent liquid outlet is formed in the side face of the bottom of the second precipitating agent storage tank 18, and the direction of the liquid outlet is parallel to the middle intercepting screen. This kind of special design of second precipitant storage tank 18 can reduce the storage tank volume, practices thrift the space, changes the precipitant at any time and can guarantee the extremely low monomer in the polyester product and solvent residual content, and in addition, limited storage tank volume can also avoid later stage solid-liquid separation difficulty.

In the embodiment of the invention, the second separator is selected from a small oscillating screen, and can meet the requirement of solid-liquid separation in the later period.

To achieve a low residual solvent content, the purified polyester product is dried in a manner selected from the group consisting of air drying, vacuum drying, and freeze drying, with air drying being preferred for the drying effect of the embodiments of the present invention.

In the embodiment of the present invention, the lower side surface of the second precipitator storage tank 18 is provided with a second precipitator inlet and a second precipitator outlet, wherein the second precipitator inlet is disposed on one side surface of the lower middle portion of the second precipitator storage tank 18 at an angle of 45 ° upward from the inclination, and the second precipitator outlet is disposed on the other side surface of the bottom of the second precipitator storage tank 18 at an angle of 0 ° from the horizontal.

The method provided by the embodiment of the invention can be used for economically and effectively producing industrial batch polyester products with constant quality. The steps of the embodiments of the present invention provide continuous operability that can ensure product consistency between batches regardless of batch size.

The contact part of the production equipment provided by the embodiment of the invention and the material is made of 316L stainless steel, so that the high quality and low emigration required by pharmacy are ensured.

Example 3:

adding 20L of acetone into the first solution storage tank 1, and weighing glycolide-lactide copolymer (75: 25, Mw11000 Da) 2kg, adding the first solution storage tank 1, starting an overhead stirring paddle 2 (400 rpm) to stir and dissolve the first solution, and keeping the temperature to 25 ℃; adding 10L of water for injection into a first precipitator storage tank 4, keeping the temperature to 25 ℃, transferring the water in the first precipitator storage tank 4 into a first solution storage tank 1 through a feeding lining pipe 3 at a constant speed, and gradually separating out a polyester product; introducing the formed polyester suspension into a feed inlet 7 of a conical separator at the flow rate of 7L/min, allowing the polyester suspension to enter the conical separator 8 for solid-liquid separation, enriching the separated syrup-like polyester precipitate through a discharge outlet 9 of the conical separator, transferring the concentrated syrup-like polyester precipitate to a second solution storage tank 12, and discharging the supernatant from a clear liquid outlet 10 of the conical separator; subsequently, 6L of acetone is added into a second solution storage tank 12 to redissolve the polyester precipitate, the redissolved polyester solution is transferred to a two-fluid nozzle feed liquid inlet 15 through a feed liquid transfer pipe 14, compressed air is introduced into a two-fluid nozzle gas inlet 16, a two-fluid nozzle main body 17 is placed under the liquid level of a second precipitator, the polyester solution is crushed and sprayed into a large number of second precipitator storage tanks 18 under the action of air flow, a precipitator side liquid inlet 23 and a precipitator top liquid inlet 25 are kept in an open state, the precipitator is updated every 30s, a precipitator bottom liquid outlet 22 is kept in an open state, and the precipitator containing a large number of monomers and solvents is periodically discharged. After the polyester solution in the second solution storage tank 12 is completely precipitated, the precipitant in the second precipitant storage tank 18 is completely updated, the liquid outlet 22 at the bottom of the precipitant is closed, the polyester precipitation slag discharging port 24 is opened, the polyester precipitate is discharged along with the precipitant, and then enters the oscillating screen 27 for concentration, and finally enters the dryer 28 for drying, and after drying, uniform polyester products are obtained by crushing, and relevant detection indexes of the purified polyester products are shown in tables 1-2.

TABLE 1 comparison of molecular weight detection indexes of polyester products before and after purification

Detecting items	Mw	Mn	Mp	PDI
					Polymer before purification	11676	6575	11465	1.80
Purified polymer	11730	7493	11419	1.48

As can be seen from the results in Table 1, the purification method of the present invention can significantly remove oligomers in polyester products, and the purified polyester has narrow molecular weight distribution, little change in weight average molecular weight, and increased number average molecular weight.

TABLE 2 comparison of residual index of monomer and solvent in polyester products before and after purification

Remarking: the star mark detection index is that reagent is introduced in the polyester synthesis process and is completely removed after purification.

As can be seen from the results in Table 2, the purification method of the present invention can significantly remove the monomer components in the polyester product, and the solvent residue in the purified polyester product is also kept at a very low level.

The method and the equipment can be suitable for separating and purifying polyester in any range, thereby obtaining satisfactory products.

Other embodiments of the present application will be apparent to those skilled in the art from consideration of the specification and practice of the disclosure disclosed herein. This application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the application and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the application being indicated by the following claims.

It will be understood that the present application is not limited to the precise arrangements described above and shown in the drawings and that various modifications and changes may be made without departing from the scope thereof. The scope of the application is limited only by the appended claims.