阅读说明：本技术 一种连续制备聚乙交酯和丙交酯嵌段共聚物的方法和装置 (Method and device for continuously preparing polyglycolide and lactide block copolymer ) 是由 康小玲 梁勇军 唐曦 郑柏川 孙文兵 邓任军 于 2021-10-08 设计创作，主要内容包括：本发明属于高分子化工技术领域,具体公开了一种连续制备聚乙交酯和丙交酯嵌段共聚物的方法和装置。所述方法为：在催化剂、引发剂作用下,第一单体经预聚反应得第一单体预聚物；然后第二单体与第一单体预聚物混合反应得由第一单体-第二单体嵌段共聚物,为PLA-PGA或PGA-PLA形式；接着嵌段共聚物进行本体聚合反应,进一步增大分子量,最后进行封端脱挥,得到聚乙交酯和丙交酯嵌段共聚物。采用本方法可连续合成规则的、具有特定分子结构的聚乙交酯和丙交酯嵌段共聚物(即PLGA共聚物),产品分子结构易于控制,产品品质稳定,分子量高,单体含量低,有利于工程放大,实现大规模生产。(The invention belongs to the technical field of polymer chemical industry, and particularly discloses a method and a device for continuously preparing polyglycolide and lactide block copolymer. The method comprises the following steps: under the action of a catalyst and an initiator, a first monomer is subjected to prepolymerization reaction to obtain a first monomer prepolymer; then, mixing and reacting the second monomer with the prepolymer of the first monomer to obtain a first monomer-second monomer block copolymer in a PLA-PGA or PGA-PLA form; then the block copolymer is subject to bulk polymerization reaction to further increase molecular weight, and finally the end capping and devolatilization are carried out to obtain the polyglycolide and lactide block copolymer. The method can continuously synthesize regular polyglycolide and lactide block copolymer (i.e. PLGA copolymer) with specific molecular structure, the molecular structure of the product is easy to control, the product quality is stable, the molecular weight is high, the monomer content is low, the engineering amplification is facilitated, and the large-scale production is realized.)

1. A method for continuously preparing polyglycolide and lactide block copolymer, comprising the steps of: under the action of a catalyst and an initiator, carrying out ring-opening polymerization on a first monomer, and carrying out prepolymerization reaction to obtain a first monomer prepolymer; then adding a second monomer into the first monomer prepolymer, fully mixing and reacting, and further carrying out ring-opening polymerization on the second monomer under the action of a terminal hydroxyl group formed by polymerization of the first monomer and a catalyst to obtain a block copolymer formed by the first monomer and the second monomer, wherein the block copolymer is in a PLA-PGA or PGA-PLA form; then the block copolymer is subjected to bulk polymerization reaction to further increase the molecular weight; after the polymerization reaction is finished, performing end-capping devolatilization on the obtained product to obtain a polyglycolide-lactide block copolymer; when the first monomer is lactide, the second monomer is glycolide; when the first monomer is glycolide, the second monomer is lactide.

2. The method of claim 1, wherein: the lactide is selected from at least one of L-lactide, D-lactide and Meso-lactide;

and/or the catalyst is at least one of a tin catalyst, a titanium catalyst, a germanium catalyst, an antimony catalyst, a metallocene catalyst, an alkali metal and a hydroxide thereof;

and/or the initiator is selected from at least one of ethanol, n-hexanol, 1-butylamine and butanol;

and/or the blocking agent adopted during blocking is at least one selected from terephthalic acid, benzoic acid, adipic acid, glycidyl methacrylate, acrylic hydrophobic glyceride and derivatives thereof, hexamethylene diamine, phosphoric fatty alcohol esters and phosphoric acid.

3. The method of claim 1, wherein: the molar use ratio of the first monomer to the second monomer is (1-99): (99-1);

and/or the dosage of the catalyst is 0.01-0.05% of the dosage of the first monomer, and the dosage of the initiator is 0.1-0.5% of the dosage of the first monomer;

and/or the adding speed of the first monomer is 1-5L/h, the adding speed of the second monomer is 0.2-10L/h, and the adding speed of the end-capping reagent is 1-5 mL/h.

4. The method of claim 1, wherein: when the first monomer is lactide, the polymerization degree of the first monomer prepolymer is 5-1000; when the first monomer is glycolide, the polymerization degree of the first monomer prepolymer is 10-5000.

5. The method of claim 1, wherein: the prepolymerization reaction temperature is 100-180 ℃;

and/or the mixing and reaction temperature of the first monomer prepolymer and the second monomer is 120-200 ℃;

and/or the temperature of the polymerization reaction is 150-250 ℃;

and/or the reaction temperature of the end-capping devolatilization is 200-250 ℃, and the pressure is 1000-1500 Pa.

6. An apparatus for continuously preparing polyglycolide and lactide block copolymer, characterized in that: the device comprises a prepolymerization reactor, a second monomer mixer, a polymerization reactor and an end-capping devolatilization reactor which are sequentially arranged along the reaction direction, wherein the prepolymerization reactor is a place where a first monomer is subjected to ring-opening polymerization to form a first monomer prepolymer through prepolymerization, the second monomer mixer is a place where the first monomer prepolymer and a second monomer are mixed and subjected to ring-opening polymerization to form a first monomer-second monomer block copolymer, the polymerization reactor is a place where the first monomer-second monomer block copolymer is subjected to further polymerization reaction to further increase the molecular weight, and the end-capping devolatilization reactor is a place where the first monomer-second monomer block copolymer subjected to end-capping devolatilization reaction is subjected to end-capping devolatilization reaction after the polymerization reaction is completed; when the first monomer is lactide, the second monomer is glycolide; when the first monomer is glycolide, the second monomer is lactide.

7. The apparatus of claim 6, wherein: the prepolymerization reactor is selected from one or more of a microreactor, a stirred tank reactor, a pipeline reactor, a loop reactor and a dynamic mixer;

and/or the second monomer mixer is a pipeline reactor or a dynamic mixer;

and/or, the polymerization reactor is a plug flow reactor;

and/or the end-capped devolatilization reactor has two different structural forms:

the first one includes static mixer and devolatilizer, the static mixer is the place where the blocking agent is mixed with the block copolymer to carry out the blocking reaction and quench the catalyst, the devolatilizer is the place where the devolatilization reaction is carried out and unreacted monomer glycolide or lactide is removed from the polymer;

and the second is a double-screw extruder, the end capping agent and the block copolymer are mixed through the double-screw extruder to perform end capping reaction, and then vacuum devolatilization is directly completed in the double-screw extruder to obtain the copolymer of polyglycolide and lactide with high molecular weight and low monomer content.

8. The apparatus of claim 7, wherein: the loop reactor comprises a conveying pump, a mixing device and a plurality of pipeline reactors connected in series in an annular shape, wherein the conveying pump, the mixing device and the pipeline reactors are sequentially connected end to end; preferably, in the loop reactor, the number of pipeline reactors is 2-5;

and/or the plug flow reactor is a tubular or tower reactor, the plug flow reactor comprises a shell, a first distributor, a plurality of sections of heat exchange mixing units and a second distributor which are connected with each other are sequentially arranged in the shell from top to bottom, each section of heat exchange mixing unit comprises a heat exchange mixing element, a packing supporting plate and a packing pressing plate, the shell provides a circulating channel for reactants and products and provides arrangement space and support for the heat exchange mixing elements, each layer of heat exchange mixing element consists of a plurality of layers of staggered and coiled heat exchange tubes, each layer of heat exchange tubes consists of a plurality of pairs of staggered and arranged heat exchange tubes, and the whole shell space is filled with the plurality of pairs of heat exchange tube groups; the heat exchange mixing element is characterized in that a gap between the shell and the heat exchange mixing element is loaded with a filler, the filler supporting plate is arranged below the heat exchange mixing element and used for supporting the filler and the heat exchange mixing element, the filler pressing plate is arranged above the heat exchange mixing element and used for pressing and fixing the filler, and both the filler supporting plate and the filler pressing plate are of sieve pores or sieve mesh structures; the top and the bottom of the shell are respectively provided with a material inlet and a material outlet, the upper end and the lower end of the first distributor are respectively connected with the material inlet and the heat exchange mixing unit positioned at the uppermost part, the upper end and the lower end of the second distributor are respectively connected with the heat exchange mixing unit positioned at the lowermost part and the material outlet, and the side wall of the shell is provided with a plurality of cold and hot medium inlets and outlets communicated with the heat exchange tubes; and a temperature detection element is also arranged in the plug flow reactor.

9. The apparatus of claim 6, wherein: a feed system is also included.

10. The apparatus of claim 9, wherein: the feeding system comprises a first monomer metering pump, a second monomer metering pump, an initiator metering pump, a catalyst metering pump and an end capping agent metering pump.

Technical Field

The invention relates to the technical field of high polymer chemical industry, in particular to a method and a device for continuously preparing polyglycolide and lactide block copolymer.

Background

With the continuous development of polymer chemistry and the continuous enhancement of environmental awareness of people, degradable polymer materials receive more and more attention. In the existing degradable high polymer materials, polylactic acid is a well-known star product due to the highest cost performance and excellent degradability. With the continuous development of the coal chemical industry technology, the structure of the coal chemical industry is continuously upgraded, the preparation of glycolic acid from coal is a new industry, and the derived polyglycolic acid product also becomes a hot spot of the current degradable material. Glycolide has also been widely accepted for its excellent heat resistance, higher barrier properties, and excellent degradability. However, glycolide is easy to crystallize, has a melting point of 220 ℃ or higher, requires a high processing temperature, and is easy to degrade during processing. Therefore, if polylactide and polyglycolide are copolymerized, the advantages can be complemented, the barrier property of PLGA (glycolide-lactide copolymer) copolymerization is improved, crystallization is reduced, the processing temperature is reduced, the service life is prolonged, and new applications can be realized in many fields.

PLGA (glycolide-lactide copolymer) is a bioabsorbable high molecular material with adjustable degradation rate, has very good biocompatibility, can be completely absorbed in a living body, and is finally metabolized and decomposed. Therefore, the method has more researches in the medical field and also obtains wider application. However, at present, most of glycolide-lactide copolymers are obtained by direct copolymerization of L-lactide and glycolide, the copolymerization belongs to random copolymerization, and the randomness of the glycolide and the lactide is strong, so that the copolymer has unstable performance, large difference among products and difficult application.

Most of PLGA synthesis processes are limited to solution polymerization or bulk polymerization in small quantities, and are applied to the medical field, and large-scale production of PLGA block copolymers cannot be achieved. The development of a continuous PLGA block copolymer synthesis process is a precondition for market popularization of the copolymer, so that the solution of the polymerization problem has very important significance for the degradable material to replace the traditional petroleum-based plastic, further solve the most critical link of environmental pollution such as soil pollution, water pollution and the like, even reduce the emission of greenhouse gas and cater to the carbon neutralization concept.

Disclosure of Invention

In view of the above-mentioned disadvantages of the prior art, the present invention aims to provide a method and an apparatus for continuously preparing polyglycolide and lactide block copolymer, which are used to solve the problems of unstable performance, large difference between products, and inability of large-scale production of the existing PLGA block copolymer and synthesis process of the prior art.

To achieve the above and other related objects, the present invention provides a method for continuously preparing polyglycolide and lactide block copolymers, comprising the steps of:

under the action of a catalyst and an initiator, carrying out ring-opening polymerization on a first monomer, and carrying out prepolymerization reaction to obtain a first monomer prepolymer; then adding a second monomer into the first monomer prepolymer, fully mixing and reacting, and further carrying out ring-opening polymerization on the second monomer under the action of a terminal hydroxyl group formed by polymerization of the first monomer and a catalyst to obtain a block copolymer formed by the first monomer and the second monomer, wherein the block copolymer is in a PLA-PGA or PGA-PLA form; then the block copolymer is subjected to bulk polymerization reaction to further increase the molecular weight; after the polymerization reaction is finished, performing end-capping devolatilization on the obtained product to obtain a polyglycolide-lactide block copolymer; when the first monomer is lactide, the second monomer is glycolide; when the first monomer is glycolide, the second monomer is lactide.

Further, the lactide is selected from at least one of L-lactide, D-lactide and Meso-lactide.

Further, the molar use ratio of the first monomer to the second monomer is (1-99): (99-1).

Furthermore, the dosage of the catalyst is 0.01-0.05% of the dosage of the first monomer, and the dosage of the initiator is 0.1-0.5% of the dosage of the first monomer.

Further, the adding speed of the first monomer is 1-5L/h, the adding speed of the second monomer is 0.2-10L/h, and the adding speed of the end-capping reagent is 1-5 mL/h.

Further, when the first monomer is lactide, the polymerization degree of the first monomer prepolymer is 5-1000; when the first monomer is glycolide, the polymerization degree of the first monomer prepolymer is 10-5000.

In the invention, the catalyst, the initiator and the end-capping reagent can be common reagents reported in the literature.

Further, the catalyst is at least one of a tin catalyst, a titanium catalyst, a germanium catalyst, an antimony catalyst, a metallocene catalyst, an alkali metal and a hydroxide thereof; preferably, the tin catalyst is at least one selected from stannous octoate, stannous chloride dihydrate, stannic lactate and stannous benzoate.

Further, the initiator is selected from at least one of ethanol, n-hexanol, 1-butylamine and butanol.

Further, the blocking agent used in blocking is at least one selected from the group consisting of terephthalic acid, benzoic acid, adipic acid, glycidyl methacrylate, hydrophobic acrylates and derivatives thereof, hexamethylenediamine, fatty alcohol phosphates, and phosphoric acid.

Further, the prepolymerization reaction temperature is 100-180 ℃.

Further, the temperature at which the first monomer prepolymer and the second monomer are mixed and reacted is 120-200 ℃.

Further, the temperature of the polymerization reaction is 150-250 ℃.

Further, the reaction temperature of the end-capping devolatilization is 200-250 ℃, and the pressure is 1000-1500 Pa.

The invention also provides a device for continuously preparing the polyglycolide-lactide block copolymer, which comprises a pre-polymerization reactor, a second monomer mixer, a polymerization reactor and a terminal capping devolatilization reactor which are sequentially arranged along the reaction direction, wherein the pre-polymerization reactor is a place where a first monomer is subjected to ring-opening polymerization to form a first monomer pre-polymer through pre-polymerization reaction, the second monomer mixer is a place where the first monomer pre-polymer and a second monomer are mixed and subjected to ring-opening polymerization to form a first monomer-second monomer block copolymer, the polymerization reactor is a place where the first monomer-second monomer block copolymer is subjected to further polymerization reaction to further increase the molecular weight, and the terminal capping devolatilization reactor is a place where the first monomer-second monomer block copolymer subjected to terminal capping devolatilization reaction after the polymerization reaction is completed; when the first monomer is lactide, the second monomer is glycolide; when the first monomer is glycolide, the second monomer is lactide.

Further, the prepolymerization reactor is selected from one or more of a micro-reactor, a stirred tank reactor, a pipeline reactor, a loop reactor and a dynamic mixer.

Further, the second monomer mixer is a pipeline reactor or a dynamic mixer.

Further, the micro reactor comprises a material flow precise distributor, an integrated mixer and a parallel micro-channel reactor, wherein the parallel micro-channel reactor comprises a plurality of micro reaction channels which are arranged in parallel, and the micro reaction channels are provided with a feeding hole and a discharging hole; the feed inlets of the micro-reaction channels are respectively provided with an integrated mixer; the material flow precise distributor is connected with the integrated mixer, the material flow precise distributor is used for uniformly distributing the materials into a plurality of material flows with the same number as that of the micro reaction channels, and the integrated mixer is used for mixing the materials; and a cooling and heating medium baffle plate channel is arranged in the parallel micro-channel reactor.

Further, the pipeline reactor is of a tubular structure and comprises a pipeline, a mixing element arranged inside the pipeline and a temperature control jacket arranged outside the pipeline, wherein the mixing element is a heat transfer component with enhanced disturbance. The mixing unit that has different structures inside the pipeline through the inside repeated shearing and the disturbance of material in mixing unit, reaches the purpose of mixing, and mixing element in the pipeline reactor is including having the component of fluid guide effect and redistribution effect, also can be by the special coil structure that has heat transfer and mixing effect that the heat exchange tube twines through interweaving.

Further, the loop reactor comprises a conveying pump, a mixing device and a plurality of pipeline reactors connected in series in an annular shape, wherein the conveying pump, the mixing device and the pipeline reactors are sequentially connected end to end; preferably, in the loop reactor, the number of pipeline reactors is 2-5. Under the drive of the delivery pump, materials (including a catalyst, an initiator and a first monomer) for the prepolymerization reaction are continuously circulated, are mixed with newly-fed materials through a mixing device and then react in the pipeline reactor; after the reactants are circulated for one week, part of the products are extracted, and the other part of the products continuously flow circularly to carry out the reaction.

Further, the polymerization reactor is a plug flow reactor. The block copolymer is further polymerized, the molecular weight and the viscosity can be further increased, a plug flow reactor is adopted, materials flow in the reactor in a plug flow mode, and heat exchange is carried out while mixing, so that the reaction of high-viscosity fluid is realized.

Further, the plug flow reactor is a tubular or tower reactor, the plug flow reactor comprises a shell, a first distributor, a plurality of sections of heat exchange mixing units and a second distributor which are connected with each other are sequentially arranged in the shell from top to bottom, each section of heat exchange mixing unit comprises a heat exchange mixing element, a packing support plate and a packing press plate, the shell provides a channel for reactants and products to flow and provides arrangement space and support for the heat exchange mixing elements, each heat exchange mixing element comprises a plurality of layers of staggered and coiled heat exchange tubes, each layer of heat exchange tubes comprises a plurality of pairs of staggered and arranged heat exchange tubes, a plurality of pairs of heat exchange tube groups fill the whole shell space, a gap between the shell and the heat exchange mixing elements is loaded with packing, the packing support plate is arranged below the heat exchange mixing elements and is used for supporting the packing and the heat exchange mixing elements, and the packing press plate is arranged above the heat exchange mixing elements, the filler supporting plate and the filler pressing plate are both in sieve pore or screen mesh structures and used for pressing and fixing the filler; the top and the bottom of the shell are respectively provided with a material inlet and a material outlet, the upper and the lower ends of the first distributor are respectively connected with the material inlet and the heat exchange mixing unit positioned at the uppermost part, the upper and the lower ends of the second distributor are respectively connected with the heat exchange mixing unit positioned at the lowermost part and the material outlet, and the side wall of the shell is provided with a plurality of cold and heat medium inlets and outlets communicated with the heat exchange tubes; and a temperature detection element is also arranged in the plug flow reactor.

Further, the shell of the plug flow reactor is in a heat exchange type without a jacket, a full jacket, a partial jacket or a pipe.

Furthermore, in the plug flow reactor, adjacent heat exchange tubes are arranged in an interweaving way at an angle of 60-120 degrees.

Further, in the plug flow reactor, a heat exchange tube is formed in a bending mode, and the radius range of a bent tube of the heat exchange tube is 0.5-1.75 times of the diameter.

Further, in the plug flow reactor, the heat exchange mixing element is of a single-tube-pass or double-tube-pass structure.

Further, in the plug flow reactor, a packing support plate is welded or fixed to the inner wall of the shell through a fastener.

Further, in the plug flow reactor, the packing press plate is fixed on the shell through a fastener, so that the packing is convenient to disassemble, assemble and repair.

Further, in the plug flow reactor, the filler is selected from one of random filler, regular filler and woven mesh filler, the random filler comprises a metal woven mesh, pall rings and spherical filler, and the regular filler is specially-shaped filler comprising corrugated plates, silk screens, skeleton filler and the like.

Further, in the plug flow reactor, the first distributor and the second distributor are selected from at least one of a shower distributor, a round hole distributor, a static mixer-shaped distributor, a calandria distributor and a spiral pipe distributor. The concrete form of distributor selects according to the state of reactant and the direction of commodity circulation, and to gas-liquid reaction, it is more beneficial to adopt shower nozzle formula or round hole distributor, and to homogeneous reaction, it has more mixed effect to adopt static mixer formula distributor.

Further, a temperature detection element is arranged at the material inlet of the plug flow reactor and below each heat exchange mixing element.

Further, the end-capped devolatilization reactor has the following two different structural forms:

the first one includes static mixer and devolatilizer, the static mixer is the place where the blocking agent is mixed with the block copolymer to carry out the blocking reaction and quench the catalyst, the devolatilizer is the place where the devolatilization reaction is carried out and unreacted monomer glycolide or lactide is removed from the polymer; preferably, the devolatilizer is a dropped strip or slice devolatilizer;

and the second is a double-screw extruder, the end capping agent and the block copolymer are mixed through the double-screw extruder to perform end capping reaction, and then vacuum devolatilization is directly completed in the double-screw extruder to obtain the copolymer of polyglycolide and lactide with high molecular weight and low monomer content.

Further, the device for continuously preparing the polyglycolide and the lactide block copolymer also comprises a feeding system.

Further, the feeding system comprises a first monomer metering pump, a second monomer metering pump, an initiator metering pump, a catalyst metering pump and an end capping agent metering pump.

Further, the first monomer metering pump, the second monomer metering pump, the initiator metering pump, the catalyst metering pump and the end capping agent metering pump are all positive displacement pumps with heat preservation functions, and include but are not limited to a jacket diaphragm pump, a heat preservation plunger pump, a jacket gear pump and the like.

As described above, the method and apparatus for continuously preparing polyglycolide and lactide block copolymer according to the present invention have the following advantageous effects:

the invention discloses a method and a device for continuously preparing polyglycolide and lactide block copolymer, which can continuously synthesize regular polyglycolide and lactide block copolymer (i.e. PLGA copolymer) with specific molecular structure in the form of PLA-PGA or PGA-PLA, and the synthesized PLGA copolymer has the advantages of easily controlled molecular structure, stable product quality, high molecular weight, low molecular weight distribution, low monomer content, good thermal processability and thermal stability, and the like. The method and the device can realize the continuous synthesis of the PLGA copolymer, are more beneficial to engineering amplification, realize large-scale production and solve the problem of insufficient supply of the PLGA market.

Drawings

FIG. 1 is a schematic diagram showing the structure of an apparatus for continuously preparing polyglycolide and lactide block copolymers according to the present invention.

FIG. 2 shows a schematic diagram of the structure of a loop reactor according to the invention.

FIG. 3 shows a schematic diagram of the structure of a plug flow reactor according to the present invention.

FIG. 4 is a schematic diagram showing the structure of the heat exchange mixing element in the plug flow reactor of the present invention.

FIG. 5 is a schematic diagram showing the structure of the sparger in the plug flow reactor of the present invention.

Detailed Description

The embodiments of the present invention are described below with reference to specific embodiments, and other advantages and effects of the present invention will be easily understood by those skilled in the art from the disclosure of the present specification. The invention is capable of other and different embodiments and of being practiced or of being carried out in various ways, and its several details are capable of modification in various respects, all without departing from the spirit and scope of the present invention.

It should be noted that the drawings provided in the present embodiment are only for illustrating the basic idea of the present invention, and the components related to the present invention are only shown in the drawings rather than drawn according to the number, shape and size of the components in actual implementation, and the type, quantity and proportion of the components in actual implementation may be changed freely, and the layout of the components may be more complicated. The structures, proportions, sizes, and other dimensions shown in the drawings and described in the specification are for understanding and reading the present disclosure, and are not intended to limit the scope of the present disclosure, which is defined in the claims, and are not essential to the art, and any structural modifications, changes in proportions, or adjustments in size, which do not affect the efficacy and attainment of the same are intended to fall within the scope of the present disclosure. In addition, the terms "upper", "lower", "left", "right", "middle" and "one" used in the present specification are for clarity of description, and are not intended to limit the scope of the present invention, and the relative relationship between the terms and the terms is not to be construed as a scope of the present invention.

Description of reference numerals:

the system comprises a first monomer metering pump 101, a second monomer metering pump 102, an initiator metering pump 103, catalyst metering pumps 104 and 105, an end-capping agent metering pump, a prepolymerization reactor 200, a second monomer mixer 300, a polymerization reactor 400, an end-capping devolatilization reactor 500, a loop reactor 600, a conveying pump 601, a mixing device 602, a pipeline reactor 603, a take-off pump 604, a plug flow reactor 700, a shell 701, a material inlet 702, a first distributor 703, a heat exchange mixing element 704, a second distributor 705, a packing support plate 706, a packing press plate 707, a packing 708, a material outlet 709, a cooling and heating medium inlet 710 and a temperature detection element 711.

The invention provides a method for continuously preparing polyglycolide and lactide block copolymer, which comprises the following steps:

under the action of a catalyst and an initiator, carrying out ring-opening polymerization on a first monomer, and carrying out prepolymerization reaction to obtain a first monomer prepolymer; then adding a second monomer into the first monomer prepolymer, fully mixing and reacting, and further carrying out ring-opening polymerization on the second monomer under the action of a terminal hydroxyl group formed by polymerization of the first monomer and a catalyst to obtain a block copolymer formed by the first monomer and the second monomer, wherein the block copolymer is in a PLA-PGA or PGA-PLA form; then the block copolymer is subjected to bulk polymerization reaction to further increase the molecular weight; after the polymerization reaction is finished, performing end-capping devolatilization on the obtained product to obtain a polyglycolide-lactide block copolymer; when the first monomer is lactide, the second monomer is glycolide; when the first monomer is glycolide, the second monomer is lactide.

Specifically, the end-capping devolatilization reaction has two different structural forms: first, the end-capping is mixed in a static mixer, and then devolatilized by a stripping or slice devolatilizer to obtain the copolymer of polyglycolide and lactide with monomers removed. Secondly, the end capping agent and the block copolymer are mixed and reacted through a double-screw extruder, and then vacuum devolatilization is directly completed in the double-screw extruder to obtain the polyglycolide and lactide block copolymer with high molecular weight and low monomer content.

Specifically, the lactide is selected from at least one of L-lactide, D-lactide and Meso-lactide.

Specifically, the molar use ratio of the first monomer to the second monomer is (1-99): (99-1), the dosage of the catalyst is 0.01-0.05% of the dosage of the first monomer, and the dosage of the initiator is 0.1-0.5% of the dosage of the first monomer; the adding speed of the first monomer is 1-5L/h, the adding speed of the second monomer is 0.2-10L/h, and the adding speed of the end-capping reagent is 1-5 mL/h.

Specifically, when the first monomer is lactide, the polymerization degree of the first monomer prepolymer is 5-1000; when the first monomer is glycolide, the polymerization degree of the first monomer prepolymer is 10-5000.

In the invention, the catalyst, the initiator and the end-capping reagent are common reagents reported in the literature, and no special requirement is made.

Wherein the catalyst is at least one of tin catalyst, titanium catalyst, germanium catalyst, antimony catalyst, metallocene catalyst, alkali metal and hydroxide thereof; preferably, the tin catalyst is at least one selected from stannous octoate, stannous chloride dihydrate, stannic lactate and stannous benzoate. In the following examples, the catalyst used was stannous octoate.

The initiator is at least one selected from ethanol, n-hexanol, 1-butylamine and butanol. In the following examples, the initiators used are all n-hexanol.

The blocking agent used in blocking is at least one selected from terephthalic acid, benzoic acid, adipic acid, glycidyl methacrylate, acrylic hydrophobic glycerides and derivatives thereof, hexamethylenediamine, fatty alcohol phosphates, and phosphoric acid. In the following examples, the blocking agents used were all dodecyl phosphate esters.

Specifically, the prepolymerization reaction temperature is 100-180 ℃.

Specifically, the temperature for mixing and reacting the first monomer prepolymer and the second monomer is 120-200 ℃.

Specifically, the temperature of the polymerization reaction is 150-.

Specifically, the reaction temperature of the end-capping devolatilization is 200-250 ℃, and the pressure is 1000-1500 Pa.

In the invention, the prepolymerization reaction, the mixing reaction of the first monomer prepolymer and the second monomer, the polymerization reaction and the end-capping devolatilization reaction time are adjusted according to the specific actual production conditions.

The invention also provides a device for continuously preparing polyglycolide and lactide block copolymer, which comprises a feeding system, a prepolymerization reactor 200, a second monomer mixer 300, a polymerization reactor 400 and a capped devolatilization reactor 500 which are sequentially arranged along the reaction direction as shown in figure 1.

Wherein the feeding system comprises a first monomer metering pump 101, a second monomer metering pump 102, an initiator metering pump 103, a catalyst metering pump 104 and a terminating agent metering pump 105.

Specifically, the first monomer metering pump 101, the second monomer metering pump 102, the initiator metering pump 103, the catalyst metering pumps 104 and 105, and the end capping agent metering pumps are all positive displacement pumps with heat preservation functions, including but not limited to jacketed diaphragm pumps, heat preservation plunger pumps, jacketed gear pumps, and the like.

Wherein, the prepolymerization reactor 200 is a place where a first monomer forms a first monomer prepolymer through prepolymerization ring-opening polymerization, the second monomer mixer 300 is a place where the first monomer prepolymer and a second monomer are mixed and ring-opening polymerized to form a first monomer-second monomer block copolymer, the polymerization reactor 400 is a place where the first monomer-second monomer block copolymer is subjected to specific polymerization reaction to increase the molecular weight, and the end-capping devolatilization reactor 500 is a place where the first monomer-second monomer block copolymer after the polymerization reaction is subjected to end-capping devolatilization reaction; when the first monomer is lactide, the second monomer is glycolide; when the first monomer is glycolide, the second monomer is lactide.

Specifically, the prepolymerization reactor 200 is selected from one or more of a microreactor, a stirred tank reactor, a pipe reactor 603, a loop reactor 600, and a dynamic mixer, the second monomer mixer 300 is selected from the pipe reactor 603 and the dynamic mixer, and the polymerization reactor 400 is selected from the plug flow reactor 700.

The micro-reactor adopted by the invention comprises a material flow precise distributor, an integrated mixer and a parallel micro-channel reactor, wherein the parallel micro-channel reactor comprises a plurality of micro-reaction channels which are arranged in parallel, and the micro-reaction channels are provided with a feeding hole and a discharging hole; the feed inlets of the micro-reaction channels are provided with an integrated mixer; the material flow precise distributor is connected with the integrated mixer, the material flow precise distributor is used for uniformly distributing the material into a plurality of material flows with the same quantity with the micro-reaction channels, and the integrated mixer is used for mixing the material and is provided with the cooling and heating medium baffle plate channel in the parallel micro-channel reactor. The structure of the microreactor adopted by the invention can refer to a continuous-flow microreactor in the invention patent with the application number of 2020105048638, namely a method and a device for preparing polyester, polyamide and copolymer thereof by ring-opening polymerization.

The pipeline reactor adopted by the invention is of a tubular structure and comprises a pipeline, a mixing element arranged in the pipeline and a temperature control jacket arranged outside the pipeline, wherein the mixing element is a heat transfer component with enhanced disturbance. The mixing unit that has different structures inside the pipeline through the inside repeated shearing and the disturbance of material in mixing unit, reaches the purpose of mixing, and mixing element in the pipeline reactor is including having the component of fluid guide effect and redistribution effect, also can be by the special coil structure that has heat transfer and mixing effect that the heat exchange tube twines through interweaving. The structure of the pipeline reactor adopted by the invention can refer to the pipeline reactor in the invention patent with the application number of 2020105048638, namely a method and a device for preparing polyester, polyamide and copolymer thereof by ring-opening polymerization.

As shown in fig. 2, the loop reactor 600 adopted in the present invention comprises a transfer pump 601, a mixing device 602, and a plurality of pipeline reactors 603 connected in series in an annular sequence, wherein the outlet end of the last pipeline reactor 603 is connected with a production pump 604, and the production pump 604 is connected with the second monomer mixer 300; preferably, the number of pipeline reactors 603 in the loop reactor 600 is 2-5, and in fig. 2, the number of pipeline reactors 603 is 3. Under the drive of the delivery pump 601, the materials (including catalyst, initiator and first monomer) of the prepolymerization reaction are continuously circulated, and are mixed with the newly-fed materials through the mixing device 602, and then are reacted in the pipeline reactor 603; after the reactants are circulated for one week, part of the products are extracted, and the other part of the products continuously flow circularly to carry out the reaction.

As shown in fig. 3, the plug flow reactor 700 employed in the present invention is a tubular or column reactor, the plug flow reactor 700 comprising a shell 701, the shell 701 being in the form of an unsheathed, fully jacketed, partially jacketed or pipe-accompanied heat exchange pattern. The shell 701 is internally provided with a first distributor 703, a plurality of sections of heat exchange mixing units connected with each other and a second distributor 705 from top to bottom in sequence, each section of heat exchange mixing unit comprises a heat exchange mixing element 704, a filler supporting plate 706 and a filler pressing plate 707, and the shell 701 provides a circulating channel for reactants and products and provides arrangement space and support for the heat exchange mixing element 704.

As shown in fig. 4, the heat exchange mixing element 704 is composed of a plurality of layers of heat exchange tubes wound in a staggered manner, each layer of heat exchange tubes is composed of a plurality of pairs of staggered heat exchange tubes, and the space of the whole shell 701 is filled with the heat exchange tube sets; the adjacent heat exchange tubes are arranged in an interweaving way at 60-120 degrees (the angle of A in the figure 4-2 is 60 degrees, and the angle of B in the figure 4-3 is 120 degrees); the heat exchange tube is formed by bending, and the radius (R in figure 4-1) of a bent tube of the heat exchange tube is 0.5-1.75 times of the diameter. The heat exchange mixing element 704 may be selected from a single pass configuration or a dual pass configuration.

The gap between the housing 701 and the heat exchanging mixing element 704 is loaded with a filler 708, a filler support plate 706 is mounted below the heat exchanging mixing element 704 for supporting the filler 708 and the heat exchanging mixing element 704, and the filler support plate 706 may be welded to the inner wall of the housing 701 or fixed to the inner wall of the housing 701 by fasteners (e.g., screws, bolts). A packing retainer 707 is installed above the heat exchanging mixing element 704 for compressing and fixing the packing 708, and the packing retainer 707 is fixed to the housing 701 by fasteners (e.g., screws, bolts) for facilitating the assembly, disassembly and maintenance of the packing 708. Both the packing support plates 706 and the packing press plates 707 are of a mesh or screen construction. The packing 708 is selected from one of random packing 708, structured packing 708 and woven mesh packing 708, the random packing 708 comprises a metal woven mesh, pall rings and spherical packing 708, and the structured packing 708 is a packing 708 with a special shape, and comprises corrugated plates, wire meshes, skeleton packing 708 and the like.

The top and the bottom of the shell 701 are respectively provided with a material inlet 702 and a material outlet 709, the upper end and the lower end of the first distributor 703 are respectively connected with the material inlet 702 and the heat exchange mixing unit positioned at the top, the upper end and the lower end of the second distributor 705 are respectively connected with the heat exchange mixing unit positioned at the bottom and the material outlet 709, and the side wall of the shell 701 is provided with a plurality of cooling and heating medium inlets and outlets 710 communicated with the heat exchange tubes. As shown in fig. 5, the first distributor 703 and the second distributor 705 may be selected from a shower distributor, a round hole distributor (as shown in fig. 5-1), a static mixer-shaped distributor (as shown in fig. 5-4), a calandria distributor (as shown in fig. 5-2), or a spiral pipe distributor (as shown in fig. 5-3); the concrete form of distributor selects according to the state of reactant and the direction of commodity circulation, and to gas-liquid reaction, it is more beneficial to adopt shower nozzle formula or round hole distributor, and to homogeneous reaction, it has more mixed effect to adopt static mixer formula distributor.

In addition, a temperature detection element 711 is further disposed in the plug flow reactor 700, and the temperature detection element 711 is installed at the material inlet 702 of the reactor and below each heat exchange mixing element 704, so as to monitor the temperature of the reactants in each stage in the reactor in real time.

The working principle of the plug flow reactor 700 employed in the present invention is as follows:

heating medium enters and exits from the heat exchange mixing element 704 of the reactor through the cooling and heating medium inlet and outlet 710 to provide a heat exchange area, reaction raw materials enter the reactor through the material inlet 702 at the upper end of the reactor or the material outlet 709 at the lower end of the reactor (the concrete mode depends on the working conditions), the raw materials are preliminarily mixed through the first distributor 703/the second distributor 705 and the heat exchange mixing element 704, then heat exchange mass transfer reaction is carried out in the shell 701, and after the reaction is fully finished, the reaction product is discharged out of the reactor and enters the subsequent processes. The shell 701 is filled with a filler 708, which increases the contact interface between the liquid and the liquid. The temperature and flow of the heating medium/cooling medium are adjusted by the heat exchange mixing element 704, so that the reaction temperature can be accurately controlled.

The end-capped devolatilization reactor adopted by the invention has the following two different structural forms:

the first one includes static mixer and devolatilizer, the static mixer is the place where the end-capping agent is mixed with the block copolymer to carry out end-capping reaction and quench the catalyst, the devolatilizer is the place where devolatilization reaction is carried out and unreacted monomer glycolide or lactide is removed from the polymer; preferably, the devolatilizer is a dropped-strip or slice devolatilizer;

and the second is a double-screw extruder, the end capping agent and the block copolymer are mixed through the double-screw extruder to perform end capping reaction, and then vacuum devolatilization is directly completed in the double-screw extruder to obtain the copolymer of polyglycolide and lactide with high molecular weight and low monomer content.

By adopting the method and the device, the polyglycolide and lactide block copolymer is continuously prepared, and the specific embodiment is as follows:

example 1

The prepolymerization reactor adopts the combination of a microchannel reactor and a pipeline reactor, the volume of the microchannel reactor is 30mL, and the volume of the pipeline reactor is 450 mL. The second monomer mixer adopts a static mixer, the mixing element is of an sx type, and the volume is 150 mL. The polymerization reactor used a plug flow reactor having a volume of 12L. The end-capping devolatilization reactor adopts a combination of a static mixer and a falling strip devolatilization.

When preparing the block copolymer of polyglycolide and lactide, the reaction temperature of a prepolymerization reactor is controlled to be 120 ℃, the first monomer is L-lactide, the adding speed is 2.5L/h, the catalyst adopts stannous octoate, the adding amount is 0.03 percent of the adding amount of the first monomer, the initiator adopts n-hexanol, and the adding amount is 0.1 percent of the initiator. The second monomer is glycolide, and the addition amount is 1L/h. The reaction temperature of the second monomer mixer was 150 ℃ and the reaction temperature of the polymerization reactor was 200 ℃. The end-capping reagent adopts dodecyl phosphate, and the addition amount is 1.2 mL/h. The devolatilization adopts falling strip devolatilization, the devolatilization temperature is 230 ℃, and the pressure is 1200 Pa. The polymerization degree of prepolymerization reaction is controlled to be 10, the obtained PLGA is amorphous PLGA, the number average molecular weight is 14 ten thousand, the molecular weight distribution index is 1.6, the monomer content (glycolide and lactide) is 0.3 percent, the copolymer is in an amorphous state, and the polymer melting point is 220 ℃.

Example 2

The prepolymerization reactor adopts the combination of a stirred tank reactor and a pipeline reactor, the volume of the stirred tank reactor is 1000mL, and the volume of the pipeline reactor is 450 mL. The second monomer mixer adopts a static mixer, the mixing element is of an sx type, and the volume is 150 mL. The polymerization reactor used a plug flow reactor having a volume of 12L. The end-capping devolatilization reactor adopts a combination of a static mixer and a falling strip devolatilization.

When preparing the block copolymer of polyglycolide and lactide, the reaction temperature of a prepolymerization reactor is controlled to be 120 ℃, the first monomer is L-lactide, the adding speed is 4.0L/h, the catalyst adopts stannous octoate, the adding amount is 0.04 percent of the adding amount of the first monomer, the initiator adopts n-hexanol, and the adding amount is 0.2 percent of the initiator. The second monomer is glycolide, and the adding amount is 8L/h. The reaction temperature of the second monomer mixer was 150 ℃ and the reaction temperature of the polymerization reactor was 210 ℃. The end-capping reagent adopts dodecyl phosphate, and the addition amount is 4.8 mL/h. The devolatilization adopts falling strip devolatilization, the devolatilization reaction temperature is 230 ℃, and the pressure is 1200 Pa. The degree of polymerization of the prepolymerization reactor was controlled to 35, and the resulting PLGA was amorphous PLGA having a number average molecular weight of 12.6 ten thousand, a molecular weight distribution index of 1.5, a monomer content (glycolide + lactide) of 0.2%, and a copolymer which was semicrystalline and had two melting points of 164 ℃ and 216 ℃ respectively.

Example 3

The prepolymerization reactor was a loop reactor, the volume of the pipeline reactor was 2000mL, and the circulation flow was 6L/h. The second monomer mixer adopts a static mixer, the mixing element is of an sx type, and the volume is 150 mL. The polymerization reactor used a plug flow reactor having a volume of 12L. The end-capping devolatilization reactor adopts a combination of a static mixer and a falling strip devolatilization.

When preparing the polyglycolide-lactide block copolymer, the reaction temperature of a prepolymerization reactor is controlled to be 150 ℃, the first monomer is D-lactide, the adding speed is 4.0L/h, the catalyst adopts stannous octoate, the adding amount is 0.03 percent of the adding amount of the first monomer, the initiator adopts n-hexanol, and the adding amount is 0.3 percent of the initiator. The second monomer is glycolide, and the addition amount is 0.4L/h. The reaction temperature of the second monomer mixer was 150 ℃ and the reaction temperature of the polymerization reactor was 190 ℃. The end-capping reagent adopts dodecyl phosphate, and the addition amount is 1.8 mL/h. The devolatilization adopts falling strip devolatilization, the devolatilization reaction temperature is 230 ℃, and the pressure is 1200 Pa. The polymerization degree of the prepolymerization reactor is controlled to be 200, the obtained PLGA is amorphous PLGA, the number average molecular weight is 3.6 ten thousand, the molecular weight distribution index is 1.7, the monomer content (glycolide and lactide) is 0.4 percent, the copolymer is in a semi-crystalline state, and the melting point is 171 ℃.

Example 4

The prepolymerization reactor adopts the combination of a stirred tank reactor and a pipeline reactor, the volume of the stirred tank reactor is 1000mL, and the volume of the pipeline reactor is 450 mL. The second monomer mixer was a dynamic mixer with a 1500mL volume and a mixing speed of 1400 revolutions. The polymerization reactor used a plug flow reactor having a volume of 12L. The end-capping devolatilization reactor adopts a double-screw extruder.

When preparing the block copolymer of polyglycolide and lactide, the reaction temperature of a prepolymerization reactor is controlled to be 120 ℃, the first monomer is L-lactide, the adding speed is 1.0L/h, the catalyst adopts stannous octoate, the adding amount is 0.04 percent of the adding amount of the first monomer, the initiator adopts n-hexanol, and the adding amount is 0.2 percent of the initiator. The second monomer is glycolide, and the addition amount is 9L/h. The reaction temperature of the second monomer mixer was 150 ℃ and the reaction temperature of the polymerization reactor was 220 ℃. The end-capping reagent adopts dodecyl phosphate, and the addition amount is 3.6 mL/h. The end-capping devolatilization reaction adopts a double-screw extruder, the devolatilization reaction temperature is 230 ℃, and the pressure is 1200 Pa. The degree of polymerization of the prepolymerization reactor was controlled to 80 to obtain amorphous PLGA having a number average molecular weight of 27.6 ten thousand, a molecular weight distribution index of 1.4, a monomer content (glycolide + lactide) of 0.5%, a copolymer in a semicrystalline state having two melting points of 162 ℃ and 220 ℃ respectively.

Example 5

The prepolymerization reactor adopts the combination of a microchannel reactor and a pipeline reactor, the volume of the microchannel reactor is 30mL, and the volume of the pipeline reactor is 450 mL. The second monomer mixer adopts a static mixer, the mixing element is of an sx type, and the volume is 150 mL. The polymerization reactor used a plug flow reactor having a volume of 12L. The end-capping devolatilization reactor adopts a double-screw extruder.

When preparing the block copolymer of polyglycolide and lactide, the reaction temperature of a prepolymerization reactor is controlled to be 100 ℃, the first monomer is glycolide, the adding speed is 5L/h, the catalyst adopts stannous octoate, the adding amount is 0.03 percent of the adding amount of the first monomer, the initiator adopts n-hexanol, and the adding amount is 0.1 percent of the initiator. The second monomer is L-lactide with the addition of 1L/h. The reaction temperature of the second monomer mixer was 170 ℃ and the reaction temperature of the polymerization reactor was 220 ℃. The end-capping reagent adopts dodecyl phosphate, and the addition amount is 1.2 mL/h. The end capping devolatilization adopts a double-screw extruder, the devolatilization reaction temperature is 230 ℃, and the pressure is 1200 Pa. The polymerization degree of the prepolymerization reactor is controlled to be 80, the obtained PLGA is amorphous PLGA, the number average molecular weight is 11 ten thousand, the molecular weight distribution index is 1.6, the monomer content (glycolide + lactide) is 0.5 percent, the copolymer is in a semi-crystalline state, and has two melting points which are 165 ℃ and 218 ℃ respectively.

Example 6

The prepolymerization reactor adopts the combination of a microchannel reactor and a pipeline reactor, the volume of the microchannel reactor is 30mL, and the volume of the pipeline reactor is 450 mL. The second monomer mixer adopts a static mixer, the mixing element is of an sx type, and the volume is 150 mL. The polymerization reactor used a plug flow reactor having a volume of 12L. The end-capping devolatilization reactor adopts a combination of a static mixer and a falling strip devolatilization.

When preparing the block copolymer of polyglycolide and lactide, the reaction temperature of a prepolymerization reactor is controlled to be 140 ℃, the first monomer is glycolide, the adding speed is 5L/h, the catalyst adopts stannous octoate, the adding amount is 0.03 percent of the adding amount of the first monomer, the initiator adopts n-hexanol, and the adding amount is 0.1 percent of the initiator. The second monomer is D lactide with the addition of 5L/h. The reaction temperature of the second monomer mixer was 170 ℃ and the reaction temperature of the polymerization reactor was 220 ℃. The end-capping reagent adopts dodecyl phosphate, and the addition amount is 1.2 mL/h. The devolatilization adopts falling strip devolatilization, the devolatilization reaction temperature is 230 ℃, and the pressure is 1200 Pa. The polymerization degree of the prepolymerization reactor is controlled to be 15, the obtained PLGA is amorphous PLGA, the number average molecular weight is 17 ten thousand, the molecular weight distribution index is 1.3, the monomer content (glycolide and lactide) is 0.2 percent, the copolymer is in an amorphous state, and the polymer melting point is 203 ℃.

Example 7

The prepolymerization reactor adopts the combination of a stirred tank reactor and a pipeline reactor, the volume of the stirred tank reactor is 1000mL, and the volume of the pipeline reactor is 450 mL. The second monomer mixer was a dynamic mixer with a volume of 1500mL and a speed of 1450 revolutions. The polymerization reactor used a plug flow reactor having a volume of 12L. The end-capping devolatilization reactor employs a combination of static mixers and flake devolatilization.

When preparing the block copolymer of polyglycolide and lactide, the reaction temperature of a prepolymerization reactor is controlled to be 140 ℃, the first monomer is glycolide, the adding speed is 2L/h, the catalyst adopts stannous octoate, the adding amount is 0.03 percent of the adding amount of the first monomer, the initiator adopts n-hexanol, and the adding amount is 0.2 percent of the initiator. The second monomer is meso-lactide, and the adding amount is 8L/h. The reaction temperature of the second monomer mixer was 170 ℃ and the reaction temperature of the polymerization reactor was 220 ℃. The end-capping reagent adopts dodecyl phosphate, and the addition amount is 1.2 mL/h. The devolatilization adopts a thin-sheet type devolatilization, the devolatilization reaction temperature is 230 ℃, and the pressure is 1200 Pa. The polymerization degree of the prepolymerization reactor is controlled to be 300, the obtained PLGA is amorphous PLGA, the number average molecular weight is 21 ten thousand, the molecular weight distribution index is 1.3, the monomer content (glycolide and lactide) is 0.2 percent, the copolymer is a semi-crystalline polymer, and the melting point of the polymer is 217 ℃.

The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.