Method for continuously producing poly (p-dioxanone)

Abstract

The invention relates to a method for continuously producing poly (p-dioxanone), which comprises the following steps: premixing glycollic acid or a glycollic acid derivative with a ring formation catalyst, and introducing the obtained mixed material and ethylene oxide into a synthesis reaction kettle for reaction; separating and purifying the obtained reaction product, introducing the obtained purified monomer into a polymerization reaction kettle, and adding a polymerization catalyst for polymerization; after polymerization is finished, discharging is conducted, residual materials in the polymerization reaction kettle are subjected to depolymerization treatment to clean the kettle body, after depolymerization is finished, depolymerization products generated in the depolymerization treatment process are discharged, the kettle does not need to be opened for cleaning, and the next round of polymerization production is directly conducted. According to the method disclosed by the invention, the steps of synthesizing the p-dioxanone monomer, separating and purifying the monomer, catalyzing and polymerizing, depolymerizing and cleaning the kettle body and the like are continuously carried out, so that the continuous production of the poly (p-dioxanone) is realized, the side reaction of oligomerization and degradation of the p-dioxanone in storage and transportation can be avoided, and the production cost of the poly (p-dioxanone) is obviously reduced.

Description

Technical Field

[0001] This invention relates to the field of polymer preparation technology, and in particular to a method for continuous production of poly(p-dioxanone). Background Technology

[0002] Poly(p-dioxanone) is an important biodegradable polymer. Due to its good mechanical strength, high melting point, and high crystallinity, as well as excellent biocompatibility and absorbability, it is widely used in the manufacture of surgical instruments such as sutures, bone plates, and tissue repair materials. With the increasing demand for biodegradable medical materials, the industrial preparation and application research of poly(p-dioxanone) has attracted increasing attention.

[0003] Currently, the synthesis of poly(p-dioxanone) mainly relies on the ring-opening polymerization of high-purity p-dioxanone monomer. At present, the p-dioxanone monomer is mainly obtained from diethylene glycol via catalytic oxidative dehydrogenation cyclization, or from ethylene glycol via reaction with chloroacetic acid to form a carboxylate followed by esterification to form a ring. However, the acquisition of high-purity p-dioxanone monomer is primarily based on the purification of sodium p-hydroxyethoxyglycolate or the purification of the final product, p-dioxanone. For example, patent CN101824023A obtains high-purity p-dioxanone through purification, soaking, devolatilization, and vacuum distillation of sodium hydroxyethoxyglycolate; patents US5391768A, CN118994089A, CN119707911A, and CN119841801A disclose various methods for purifying p-dioxanone using crystallization; patent CN118994089A discloses a purification method for preparing crude p-dioxanone into an oligomeric solid and then depolymerizing and cyclizing it. However, the industrialization of high-purity p-dioxanone based on the above synthesis and purification methods requires large investment, has complex byproducts, involves cumbersome purification steps, and results in expensive products. Furthermore, the obtained p-dioxanone exhibits high instability, easily decomposing or degrading in quality during storage and transportation, affecting the continuous production and synthesis of poly(p-dioxanone). Current production methods for poly(p-dioxanone) mostly employ stepwise batch production, where monomer preparation and polymerization are carried out sequentially. This approach has the following drawbacks: 1. PDO monomers are prone to oligomerization or degradation during storage and transportation, leading to reduced polymerization activity; 2. Frequent reactor start-up, cleaning, and material transfer are required between process steps, resulting in complex operations and high labor intensity; 3. Reaction conditions cannot be continuously controlled, leading to significant batch-to-batch product variations; 4. High energy consumption and low equipment utilization hinder large-scale continuous production.

[0004] Therefore, designing a reasonable process for the large-scale preparation of high-purity p-dioxanone and poly(p-dioxanone) is a pressing technical problem that needs to be solved in this field. Patent CN120647620A discloses a low-cost method for preparing high-purity p-dioxanone monomer, which utilizes a one-step cyclization reaction of glycolic acid or alkyl glycolate with an epoxide compound via catalytic reaction. This synthetic method boasts high overall yield and low cost, but it does not provide corresponding technical guidance for the large-scale synthesis of p-dioxanone monomer and the industrial preparation of poly(p-dioxanone), nor does it provide any relevant conditions for achieving the large-scale continuous synthesis of p-dioxanone monomer and the continuous industrial preparation of poly(p-dioxanone).

[0005] Therefore, there is an urgent need for a process that enables continuous closed-loop production from monomer synthesis to polymerization, in order to improve production efficiency, enhance product stability, and reduce costs. Summary of the Invention

[0006] To address one or more technical problems existing in the prior art, this invention provides a method for the continuous production of poly(p-dioxanone). In this invention, glycolic acid or a glycolic acid derivative, ethylene oxide, and a cyclizing catalyst are mixed and reacted in a synthesis reactor. The reaction product is separated and purified, and the purified product is introduced into a polymerization reactor for catalytic polymerization to obtain the target product, poly(p-dioxanone). After polymerization, the material is discharged, and the reactor is cleaned by depolymerization of the residue. No reactor opening and cleaning are required, and the next round of polymerization can proceed directly. This method achieves continuous production of poly(p-dioxanone) by continuously performing the steps of dioxanone monomer synthesis, monomer separation and purification, catalytic polymerization, and depolymerization and reactor cleaning.

[0007] In a first aspect, the present invention provides a method for the continuous production of poly(p-dioxanone), the method comprising the following steps: (1) Premix glycolic acid and / or glycolic acid derivatives with a cyclization catalyst to obtain a mixture, and then pass the mixture and ethylene oxide into a synthesis reactor to carry out a cyclization reaction to obtain the reaction product; (2) Separate and purify the reaction product to obtain purified monomer, pass the purified monomer into the polymerization reactor and add polymerization catalyst into the polymerization reactor to carry out polymerization reaction; (3) After the polymerization reaction is completed, discharge the poly(p-dioxanone) obtained from the polymerization reaction and depolymerize the residue in the polymerization reactor. After the depolymerization process is completed, discharge the depolymerization products generated during the depolymerization process and carry out the next round of polymerization production.

[0008] Preferably, the cyclization reaction is carried out under an inert gas atmosphere; the pressure of the cyclization reaction is 0.1~5MPa, the temperature is 0~100℃, and the time is 0.5~12h; more preferably, the pressure of the cyclization reaction is 0.1~3MPa, the temperature is 70~100℃, and the time is 2~6h.

[0009] Preferably, the glycolic acid derivative is an alkyl glycolate, and the structural formula of the alkyl glycolate is shown in Formula I below: Formula I In Formula I, R is a C1~C6 alkyl or a C3~C6 cycloalkyl; The cyclic catalyst is selected from ferric chloride, copper tetrafluoroborate, aluminum trifluoromethanesulfonate, bismuth trifluoromethanesulfonate, and 1,8-dichlorofluorocarbonate. diazabicyclo[5.4.0]undecane 7 The alkyl glycolate is selected from one or more of the following: alkene, tetramethylammonium salt, tetraethylammonium salt, tetrabutylammonium salt, phosphazene ligand P1-tert-butyl, phosphazene ligand P2-tert-butyl, phosphazene ligand P4-tert-butyl, 2,4,6-tris[tris(dimethylamino)iminophosphine]-1,3,5-triazine, 2,4,6-tris[tris(1-pyrrolyl)iminophosphine]-1,3,5-triazine, cyclotriphosphazene base, bis(triphenylphosphine)imino salt, tetraphenylphosphonium salt, tris[tris(dimethylamino)imino]phosphazene salt, and tetra[tris(dimethylamino)imino]phosphazene salt; preferably, the alkyl glycolate is methyl glycolate, and the cyclization catalyst is bis(triphenylphosphine)ammonium chloride and / or tetrabutylammonium salt.

[0010] Preferably, the molar ratio of glycolic acid and / or glycolic acid derivative to cyclization catalyst is 1:0.0001 to 1:0.05, more preferably 1:0.002 to 1:0.02; the molar ratio of glycolic acid and / or glycolic acid derivative to ethylene oxide is 5:1 to 1:5, more preferably 1:1.1 to 1:2; and / or the ethylene oxide is introduced either once before the cyclization reaction or continuously during the cyclization reaction. Preferably, the ethylene oxide is introduced continuously during the cyclization reaction for 1 to 4 hours.

[0011] Preferably, the separation and purification is one or more of filtration, washing, distillation, rectification, and crystallization; more preferably, the separation and purification is vacuum distillation and / or vacuum rectification. The polymerization reaction is carried out under inert gas protection; and / or the temperature of the polymerization reaction is 40~160℃, preferably 80~140℃, and the time of the polymerization reaction is 1~3h.

[0012] Preferably, the temperature inside the polymerization reactor is adjusted to 100~300℃ to depolymerize the residue inside the polymerization reactor; the temperature of the depolymerization treatment is 100~300℃, and the time of the depolymerization treatment is 1~3h.

[0013] Preferably, the polymerization catalyst is one or more of tin catalyst, aluminum catalyst, transition metal catalyst, rare earth catalyst, organic base catalyst and enzyme catalyst; and / or the molar ratio of the polymerization catalyst to the purified monomer is 1:100 to 1:10000, preferably 1:500 to 1:5000.

[0014] Preferably, a depolymerization catalyst is added during the depolymerization process. The depolymerization catalyst is selected from one or more of stannous octoate, zinc oxide, magnesium oxide, zinc acetate, manganese acetate, and 1,5,7-triazabicyclo[4.4.0]dec-5-ene. In step (3), the depolymerization products generated during the depolymerization process are discharged by vacuum distillation and / or by a discharge valve. The number-average molecular weight of the poly(p-dioxane) is 800-500000 g / mol, and the viscosity-average molecular weight is 1000-800000 g / mol.

[0015] Preferably, the method is carried out using an apparatus for the continuous production of poly(p-dioxanone), the apparatus comprising: a raw material tank, a premixing vessel, a synthesis reactor, a purification device, a monomer collection tank, a polymerization reactor, and a depolymerization product collection tank; the raw material tank and the premixing vessel are connected to the feed end of the synthesis reactor, and the synthesis reactor, purification device, monomer collection tank, polymerization reactor, and depolymerization product collection tank are sequentially connected to form a continuous closed system; the purification device includes a single-stage vacuum distillation unit or multiple vacuum distillation units connected in series, each vacuum distillation unit including a vacuum distillation vessel and a distillation by-product collection tank connected to the vacuum distillation vessel; preferably, the temperature of the vacuum distillation vessel is 25~150℃; the polymerization reactor is equipped with a temperature control system, which can, after the polymerization reaction is completed, adjust the temperature of the polymerization reactor to give the polymerization reactor a depolymerization treatment function, thereby achieving a clean polymerization reactor.

[0016] Preferably, the purification apparatus includes a primary vacuum distillation unit; the vacuum distillation vessel is connected to the synthesis reaction vessel, and the vacuum distillation vessel is also connected to the monomer collection tank through a condenser; when the purification apparatus includes a primary vacuum distillation unit, the separation and purification are carried out by vacuum distillation at 25~50℃, vacuum distillation at 50~90℃, and vacuum distillation at 100~150℃ in sequence.

[0017] Compared with the prior art, the present invention has at least the following beneficial effects: (1) This invention provides a process for the continuous production of poly(p-dioxanone). From the mixing and reaction of raw materials to the separation and purification of products, further catalytic polymerization is carried out directly. Finally, the residue in the reactor is depolymerized and the reactor body is cleaned. There is no need to open the reactor for cleaning. The next round of polymerization production can be carried out directly. Through the direct cascading of the device, the large-scale preparation of high-purity p-dioxanone monomer and the continuous synthesis of poly(p-dioxanone) are realized. The overall product yield is high and the production cost is low.

[0018] (2) This invention first simplifies the monomer purification process by selecting a suitable dioxane monomer synthesis system and enables the polymerization reaction unit to have a depolymerization function. This allows for depolymerization after each round of polymerization to clean the polymerization reactor, thus avoiding the cumbersome reactor cleaning process and allowing direct entry into the next round of polymerization production. Based on this premise, this invention enables continuous production of poly(p-dioxane) monomers, including monomer synthesis, monomer separation and purification, catalytic polymerization, and depolymerization cleaning of the reactor. This design not only optimizes the production process but also successfully achieves continuous production of poly(p-dioxane). Without the aforementioned conditions, simply cascading the various processes directly would not achieve continuous production of poly(p-dioxane).

[0019] (3) The present invention uses commercial glycolic acid, alkyl glycolic acid ester and ethylene oxide as raw materials, which are widely available and low in cost; the present invention uses a cyclization catalyst to reduce side reactions, improve the conversion rate of the target product and facilitate separation and purification; the present invention uses a simple separation and purification method to achieve large-scale preparation of high-purity p-dioxanone.

[0020] (4) The method described in this invention uses a closed cascade device to directly polymerize high-purity p-dioxanone monomer to prepare poly-p-dioxanone, avoiding side reactions such as oligomerization and degradation of monomers during storage and transportation; the reactor body is cleaned by catalytic depolymerization treatment of the residue in the reactor, without the need for opening the reactor for cleaning, and the next round of polymerization production can be carried out directly, realizing a continuous process; the method of this invention has a short route, is safe and reliable, can be continuously produced, has low production cost, and high economic benefits; the device used in this invention forms a continuous production system for monomer synthesis, purification and polymerization, and can realize continuous operation of the whole process through automated control. Attached Figure Description

[0021] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. The drawings of the present invention are provided for illustrative purposes only, and the proportions, sizes, and quantities of the parts in the drawings may not be consistent with the actual product.

[0022] Figure 1 This is a flowchart of a method for continuous production of polydioxanone provided in some specific embodiments of the present invention; Figure 2 This is a schematic diagram of the structure of an apparatus for continuous production of polydioxanone according to some specific embodiments of the present invention. Figure 2 In the middle: 1: Raw material tank; 2: Premixing kettle; 3: Synthesis reactor; 4: Vacuum distillation kettle; 5: Distillation by-product collection tank; 6: Monomer collection tank; 7: Polymerization reactor; 8: Depolymerization product collection tank; 9: Vacuum pump. Detailed Implementation

[0023] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Obviously, the described embodiments are only some, not all, of the embodiments of this invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0024] In a first aspect, the present invention provides a method for the continuous production of poly(p-dioxanone), a flowchart, for example, as follows: Figure 1 As shown, the method includes the following steps: (1) Premix glycolic acid and / or glycolic acid derivatives with a cyclizing catalyst to obtain a mixture, and then introduce the mixture and ethylene oxide into a synthesis reactor to carry out a cyclization reaction to obtain the reaction product; Of course, in this invention, glycolic acid and / or glycolic acid derivatives can also be added to a synthesis reactor for premixing, and then ethylene oxide can be introduced into the synthesis reactor; In this invention, the first raw material is glycolic acid and / or glycolic acid derivatives, the second raw material is ethylene oxide, and premixing glycolic acid and / or glycolic acid derivatives with a cyclizing catalyst means premixing glycolic acid and glycolic acid derivatives with a cyclizing catalyst, or premixing glycolic acid with a cyclizing catalyst, or premixing glycolic acid derivatives with a cyclizing catalyst; (2) Separate and purify the reaction product to obtain purified monomer (also called high-purity monomer), pass the purified monomer into the polymerization reactor and add polymerization catalyst into the polymerization reactor to carry out polymerization reaction; (3) After the polymerization reaction is completed, the material is discharged to remove the poly(p-dioxanone) obtained from the polymerization reaction and to depolymerize the residue in the polymerization reactor. After the depolymerization process is completed, the depolymerization products generated during the depolymerization process are discharged to achieve a clean (self-cleaning) polymerization reactor for the next round of polymerization production. In this invention, for example, the depolymerization products of the product during the depolymerization process are discharged into the depolymerization product collection tank and / or discharged through the discharge valve at the bottom (lower end) of the polymerization reactor, and then purified monomers are introduced into the polymerization reactor to directly carry out the next round of polymerization production.

[0025] It should be noted that although the present invention adds a polymerization catalyst in the polymerization reaction, a depolymerization catalyst can also be added during the depolymerization process. However, the trace amount of catalyst remaining in the polymerization reactor has little effect on the polymerization and does not affect continuous production. Furthermore, in the present invention, it is preferred to clean the production line after 10 to 20 rounds of polymerization.

[0026] This invention involves a cyclization reaction of glycolic acid and / or glycolic acid derivatives, ethylene oxide, and a cyclization catalyst within a synthesis reactor. The reaction product (also referred to as the crude product) is separated and purified, then introduced into a polymerization reactor for catalytic polymerization to obtain the target product, poly(p-dioxanone). After polymerization, the product is discharged, and the reactor is cleaned by depolymerization of the residue. No further cleaning is required before proceeding to the next round of polymerization. This method utilizes readily available chemical raw materials, directly cascading a monomer synthesis reactor, a monomer separation and purification unit, and a polymerization reactor to form a continuous system for monomer synthesis, purification, and polymerization. This allows for the continuous execution of steps such as cyclization, separation and purification, catalytic polymerization, and depolymerization and reactor cleaning, enabling continuous production of poly(p-dioxanone). It avoids side reactions such as oligomerization and degradation of dioxanone during storage and transportation, and significantly reduces the production cost of poly(p-dioxanone).

[0027] This invention first simplifies the monomer purification process by selecting a suitable dioxane monomer synthesis system and enables the polymerization unit to perform depolymerization. This allows for depolymerization after each polymerization cycle to clean the polymerization reactor, avoiding cumbersome reactor cleaning steps and allowing direct entry into the next polymerization cycle. Based on this premise, this invention enables continuous production of poly(p-dioxane) monomers, including monomer synthesis, monomer separation and purification, catalytic polymerization, and reactor cleaning. This design not only optimizes the production process but also successfully achieves continuous production of poly(p-dioxane). Without the aforementioned conditions, simply cascading the processes directly would not achieve continuous production of poly(p-dioxane).

[0028] This invention, for example, achieves large-scale preparation of high-purity p-dioxanone monomer through a simple separation and purification method via a catalytic reaction of alkyl glycolate and epoxy compound. This monomer can be directly used to prepare poly(p-dioxanone) in a continuous closed system, and the biodegradability of the polymer is utilized to clean the reactor, thereby establishing a continuous production process suitable for large-scale applications.

[0029] According to some preferred embodiments, the cyclization reaction is carried out under the protection of an inert gas (e.g., nitrogen); the pressure of the cyclization reaction is 0.1~5 MPa, the temperature is 0~100℃, and the time is 0.5~12 h; preferably, the pressure of the cyclization reaction is 0.1~3 MPa, the temperature is 70~100℃, and the time is 2~6 h.

[0030] According to some preferred embodiments, the glycolic acid derivative is an alkyl glycolate, and the structural formula of the alkyl glycolate is shown in Formula I below: Formula I In Formula I, R is a C1~C6 alkyl or a C3~C6 cycloalkyl; The cyclic catalyst is selected from ferric chloride, copper tetrafluoroborate, aluminum trifluoromethanesulfonate, bismuth trifluoromethanesulfonate, and 1,8-dimethylamine trichloride. Diazabicyclo[5.4.0]undecane 7 Alkene (DBU), tetramethylammonium salt (TMAX, X = OH, Cl, Br, I, AcO), tetraethylammonium salt (TEAX, X = OH, Cl, Br, I, AcO), tetrabutylammonium salt (TBAX, X = OH, Cl, Br, I, AcO), phosphazene ligand P1-tert-butyl ( t -BuP1), phosphazene ligand P2-tert-butyl ( t -BuP2), phosphazene ligand P4-tert-butyl ( t One or more of the following: -BuP4), 2,4,6-tris[tris(dimethylamino)iminophosphine]-1,3,5-triazine (C3N3-Me-P3), 2,4,6-tris[tris(1-pyrrolyl)iminophosphine]-1,3,5-triazine (C3N3-Py-P3), cyclotriphosphazene base (CTPB), bis(triphenylphosphine)imino salt (PPNX, X = Cl, Br, I), tetraphenylphosphonium salt (TPPX, X = Cl, Br, I), tris[tris(dimethylamino)imino]phosphazene salt (P4X, X = Cl, Br, I), tetras[tris(dimethylamino)imino]phosphazene salt (P5X, X = Cl, Br, I); the partially cyclic catalysts of the present invention are shown below.

[0031] According to some preferred embodiments, the alkyl glycolate is methyl glycolate, and the cyclization catalyst is bis(triphenylphosphine)ammonium chloride and / or tetrabutylammonium salt.

[0032] According to some preferred embodiments, the ethylene oxide is high-pressure liquefied ethylene oxide with a purity >99%.

[0033] According to some preferred embodiments, the molar ratio of glycolic acid and / or glycolic acid derivatives to the cyclizing catalyst (i.e., the molar ratio of the first raw material to the cyclizing catalyst) is 1:0.0001 to 1:0.05, preferably 1:0.002 to 1:0.02.

[0034] According to some preferred embodiments, the molar ratio of glycolic acid and / or glycolic acid derivatives to ethylene oxide (i.e., the molar ratio of the first raw material to the second raw material) is 5:1 to 1:5, preferably 1:1.1 to 1:2; during the cyclization reaction, it is preferable to use an excess of ethylene oxide. This invention employs a strategy of using an excess of ethylene oxide. This invention has found that in the continuous production process of poly(p-dioxane), the excessive use of ethylene oxide is advantageous because it can be effectively separated after the reaction, avoiding impact on product purity and helping to improve reaction conversion rate. In contrast, if the amount of glycolic acid and / or alkyl glycolate in the synthesis reactor is excessive, it will adversely affect the continuity of the entire production process. Excess glycolic acid and / or alkyl glycolate increases the difficulty of subsequent monomer separation and purification. The design in this invention makes the process simpler and more efficient, improving reaction selectivity and reducing production costs. Especially in the later monomer separation and purification stages, excess ethylene oxide can be easily removed, while excess glycolic acid and / or alkyl glycolate may lead to complex separation processes. Therefore, this invention, by employing an excess ethylene oxide design, successfully achieves the continuous production of poly(p-dioxanone), demonstrating outstanding industrial application prospects.

[0035] According to some preferred embodiments, the ethylene oxide is introduced either in a single addition before the cyclization reaction or continuously during the cyclization reaction. Preferably, the ethylene oxide is continuously added during the cyclization reaction for 1-4 hours. Ethylene oxide is a highly hazardous chemical; continuous addition during the cyclization reaction can promote the reaction while avoiding a sudden increase in pressure inside the reactor caused by introducing ethylene oxide before or within a short period of time. Therefore, this invention, through a rationally designed method of adding ethylene oxide, effectively ensures the safety of continuous production of poly(p-dioxanone), demonstrating a promising industrial application prospect.

[0036] According to some preferred embodiments, the separation and purification includes one or more of filtration, washing, distillation, rectification, and crystallization. That is, the separation and purification mainly includes treating the reaction products generated by the cyclization reaction through one or more of the following steps: filtration, washing, distillation, rectification, and crystallization. Preferably, the separation and purification is vacuum distillation and / or vacuum rectification. The polymerization reaction is carried out under the protection of an inert gas (e.g., nitrogen). And / or the temperature of the polymerization reaction is 40~160℃, preferably 80~140℃, and the time of the polymerization reaction is 1~3h.

[0037] According to some preferred embodiments, the temperature inside the polymerization reactor is adjusted to 100~300℃ to depolymerize the residue inside the polymerization reactor; the depolymerization temperature is 100~300℃, and the depolymerization time is 1~3h; in this invention, the depolymerization process includes depolymerizing the residue inside the polymerization reactor at a temperature of 100~300℃ after discharge to clean the reactor body, without the need for opening the reactor for cleaning, and directly proceeding to the next round of polymerization production.

[0038] According to some preferred embodiments, the polymerization catalyst is one or more selected from tin catalysts, aluminum catalysts, transition metal catalysts, rare earth catalysts, organic base catalysts, and enzyme catalysts; preferably, the tin catalyst is selected from one or more selected from stannous octoate, stannous oxalate, di-n-butyldistannous octoate, stannous acetylacetonate, dibutyltin oxide, and di-n-butyltin oxide; preferably, the aluminum catalyst is selected from one or more selected from aluminum methoxide, aluminum ethoxide, aluminum isopropoxide, aluminum sec-butoxide, aluminum tert-butoxide, aluminum phenoxy, aluminum neopentyl alcohol, porphyrin aluminum complexes, and triethylaluminum-water-phosphoric acid systems; preferably, the transition metal catalyst is selected from one or more selected from diethylzinc, zinc lactate, ferric iron (2,4-pentanedione), ferric iron (2,4-pentanedione), and zirconium tetra(acetylacetonate); preferably, the rare earth catalyst is selected from yttrium isopropoxide, yttrium isopropoxide, and zirconium tetra(acetylacetonate)oxo. Lanthanum alkoxide, praseodymium isopropoxide, neodymium isopropoxide, gadolinium isopropoxide, tri(acetylacetone)yttrium, tri(acetylacetone)lanthanum, tri(acetylacetone)neodymium, tri(acetylacetone)samarium, tri(acetylacetone)ytterbium, tris(2,6-di-tert-butylphenoxy)yttrium, tris(2-ethoxyethyl)yttrium alkoxide, tris(2-(N-methylamino)ethyl)yttrium alkoxide, di(ethyl acetate)yttrium, tris[bis(trimethylsilyl)amino]yttrium, tetra(tetra(tetrazolium))yttrium, The organic base catalyst is selected from one or more of the following: tri(aryloxy)smarium, tri(aryloxy)lanthanum, tri(N-phenylethyl-3,5-di-tert-butylsalicylaldehydeimine)lanthanum, dimethylsilamidolanthanum-dimethoxyethyl ether complex, dimethylsilamidone-neodymium-dimethoxyethyl ether complex, dimethylsilamidosmarium-dimethoxyethyl ether complex, and amine-bridged bisphenol Yttrium guanidine; preferably, the organic base catalyst is selected from the phosphazene ligand P4-tert-butyl( t-BuP4), cyclotriphosphazene base (CTPB), bis(triphenylphosphine)imino salt (PPNX, X = Cl, Br, I), tris[tris(dimethylamino)imino]phosphazene salt (P4X, X = Cl, Br, I), tetra[tris(dimethylamino)imino]phosphazene salt (P5X, X = Cl, Br, I), 1,8-diazabicyclo[5.4.0]undecene-7-ene, 1,5,7-triazabicyclo[4.4.0]decene-5-ene, 4-dimethylaminopyridine, diphenyl phosphate, or one or more of these; preferably, the enzyme catalyst is Antarctic yeast lipase; and / or the molar ratio of the polymerization catalyst to the purified monomer is 1:100 to 1:10000, preferably 1:500 to 1:5000.

[0039] According to some preferred embodiments, the polymerization catalyst is selected from one or more of tin catalysts, aluminum catalysts, and organic base catalysts.

[0040] According to some preferred embodiments, a depolymerization catalyst is also added during the depolymerization process, that is, a depolymerization catalyst is added to the polymerization reactor. Preferably, the depolymerization catalyst is selected from one or more of stannous octoate, zinc oxide, magnesium oxide, zinc acetate, manganese acetate, and 1,5,7-triazabicyclo[4.4.0]dec-5-ene; and / or the amount of the depolymerization catalyst is 0.001~1wt% of the mass of the residue in the polymerization reactor after the polymerization reaction is completed; in step (3), the depolymerization products generated during the depolymerization process are discharged by vacuum distillation and / or by a discharge valve; and / or the number average molecular weight of the poly(p-dioxane) is 800~500000 g / mol, and the viscosity average molecular weight is 1000~800000 g / mol.

[0041] In this invention, the use of "and / or" between multiple technical features indicates that these technical features are connected by an "and / or" relationship, meaning that it can be any one of these technical features, or any combination of two or more of these technical features.

[0042] According to some preferred embodiments, the method is carried out using an apparatus for the continuous production of poly(p-dioxanone), such as... Figure 2 As shown, the device includes: The system comprises a raw material tank 1, a premixing kettle 2, a synthesis reactor 3, a purification device, a monomer collection tank 6, a polymerization reactor 7, and a depolymerization product collection tank 8. The raw material tank and premixing kettle are connected to the feed end of the synthesis reactor; specifically, the raw material tank and premixing kettle are connected to the feed end of the synthesis reactor via pipelines. The synthesis reactor, purification device, monomer collection tank, polymerization reactor, and depolymerization product collection tank are sequentially connected to form a continuous closed system. Specifically, for example, the synthesis reactor, purification device, monomer collection tank, and polymerization reactor are sequentially connected to the feed end of the subsequent device via pipelines. The polymerization reactor has a distillation outlet, which is connected to a condenser on the depolymerization product collection tank via a pipeline. That is, the polymerization reactor is sequentially connected to the depolymerization product collection tank via pipelines and a condenser, forming a continuous closed production system for monomer synthesis, purification, and polymerization. Continuous operation of the entire process can be achieved through automated control. The purification device includes a single-stage vacuum distillation unit or multiple vacuum distillation units connected in series. Each vacuum distillation unit includes one... The apparatus comprises a vacuum distillation kettle and a distillation by-product collection tank connected to the vacuum distillation kettle; the polymerization reactor is equipped with a temperature control system, which can, after the polymerization reaction is completed, adjust the temperature of the polymerization reactor (e.g., adjust it to 100~300℃) to enable depolymerization treatment, and clean (self-clean) the polymerization reactor by passing the depolymerization products generated during the depolymerization treatment into the depolymerization product collection tank, for example, by vacuum distillation. The polymerization reactor can clean the reactor body by depolymerizing the residue after polymerization, and the apparatus can proceed to the next round of polymerization production without opening the reactor for cleaning, realizing the continuous synthesis of poly(p-dioxanone), avoiding oligomerization and degradation reactions during monomer storage and transportation. The apparatus of the present invention is preferably suitable for the synthesis process of poly(p-dioxanone) using alkyl glycolate and ethylene oxide as raw materials; in the present invention, the depolymerization product collection tank is used to collect the depolymerization products generated during the depolymerization treatment.

[0043] According to some preferred embodiments, the purification apparatus includes a single-stage vacuum distillation unit, for example, such as... Figure 2As shown; the vacuum distillation vessel 4 is connected to the synthesis reactor, and the vacuum distillation vessel 4 is also connected to the monomer collection tank via a condenser; specifically, for example, the vacuum distillation vessel 4 is connected to the monomer collection tank 6 via a main pipeline and a condenser, and the vacuum distillation vessel 4 is connected to the distillation by-product collection tank 5 via a secondary pipeline and a condenser, that is, the distillation outlet of the vacuum distillation vessel is connected to the condenser on the monomer collection tank via a main pipeline, and is connected to the condenser on the distillation by-product collection tank via a secondary pipeline, so as to remove excess raw materials and by-products by vacuum distillation; in this invention, for example, the vacuum distillation vessel includes a stirred vessel with a feed end and a temperature control system; In this invention, when the purification apparatus includes a first-stage vacuum distillation unit, the separation and purification are performed sequentially by vacuum distillation at 25-50°C, 50-90°C, and 100-150°C. This invention does not specify the time for vacuum distillation; those skilled in the art can choose conventionally, for example, sequentially performing vacuum distillation at 25-50°C for 20-40 minutes, at 50-90°C for 1-3 hours, and at 100-150°C for 2-4 hours. In the first-stage vacuum distillation process of this invention, excess ethylene oxide is first removed by low-temperature (25-50°C) vacuum distillation to avoid its impact on the purity of the PDO monomer. Next, byproduct alcohols are removed by medium-temperature (50-90°C) vacuum distillation. This step helps to remove byproducts generated during the reaction, further improving the purity of the PDO monomer. Finally, the PDO monomer is distilled off in a high-temperature (100~150℃) vacuum distillation stage to ensure the separation and purification of the PDO monomer, which helps to obtain a high-purity final product. The purity of the PDO monomer can be no less than 99%. This method is simple and efficient, and is suitable for large-scale continuous production. It has a significant effect on the removal of by-products in the separation process and can guarantee the purity and quality of the final product.

[0044] According to some preferred embodiments, when the purification apparatus includes multiple (two or more) vacuum distillation units connected in series, the separation and purification performed in the first-stage vacuum distillation unit is sequential vacuum distillation at 25-50°C (e.g., 20-40 min), 50-90°C (e.g., 1-3 h), and 100-150°C (e.g., 2-4 h). The separation and purification performed in other stages of vacuum distillation units are sequential vacuum distillation at 50-90°C (e.g., 1-3 h) and 100-150°C (e.g., 2-4 h). In this invention, the multi-stage vacuum distillation system can optimize the separation efficiency of each stage through multiple separation stages, thereby improving the purity of the final product. This method is particularly suitable for production processes requiring extremely high purity monomers, further improving product quality.

[0045] According to some preferred embodiments, the synthesis reactor, distillation by-product collection tank, monomer collection tank and depolymerization product collection tank are connected to a vacuum pump. The vacuum pump is used to perform vacuum distillation and transfer of materials from the previous stage to the next stage.

[0046] According to some preferred embodiments, the depolymerization product collection tank is connected to the polymerization reactor via a condenser; a discharge valve is provided at the lower end (bottom) of the vacuum distillation vessel, the distillation by-product collection tank, the polymerization reactor, and / or the depolymerization product collection tank; and / or a feed port for adding catalyst is provided at the upper end of the polymerization reactor; during the polymerization reaction, the catalyst is a catalyst used for the polymerization reaction, and during the depolymerization treatment, a catalyst (depolymerization catalyst) for the depolymerization treatment can be added through the feed port.

[0047] According to some preferred embodiments, the premixing vessel is used for premixing glycolic acid with a cyclizing catalyst, or for premixing alkyl glycolate with a cyclizing catalyst, or for premixing glycolic acid and alkyl glycolate with a cyclizing catalyst; the raw material tank stores ethylene oxide; the method of the present invention is preferably applicable to the synthesis process of poly(p-dioxanone) using glycolic acid and / or alkyl glycolate and ethylene oxide as raw materials; the selection of this raw material system is not accidental or arbitrary, but rather the inventors discovered that the cyclization reaction of glycolic acid and / or alkyl glycolate with ethylene oxide can effectively reduce the formation of by-products. Unlike other raw material systems, using this raw material system ensures that the by-products are only water and / or alcohols, which not only makes the reaction process simpler. This method is efficient and significantly simplifies subsequent monomer separation and purification. High-purity p-dioxanone can be produced on a large scale using a simple separation and purification method, optimizing the continuous production process of poly(p-dioxanone). In contrast, other raw material systems often generate complex byproducts, leading to difficulties in separation and purification and significantly increased costs. This makes it difficult to achieve the required purity of monomers for continuous polymerization of p-dioxanone through continuous production routes. The method in this invention fully considers the needs of continuous production. The use of glycolic acid and / or alkyl glycolate and ethylene oxide allows the entire reaction process to proceed stably and efficiently to produce p-dioxanone without compromising reaction efficiency. This reaction system has a high reaction conversion rate, providing favorable conditions for subsequent product purification. The continuous production achieved through the design and application of this raw material system has high industrial application prospects.

[0048] According to some preferred embodiments, a flow control device is provided on the pipeline connecting the premixing vessel and the synthesis reactor and / or the raw material tank and the synthesis reactor to stabilize and control the feed flow rate of the raw material to the synthesis reactor; in this invention, the flow control device may, for example, include a dynamic flow balancing valve for controlling the feed rate.

[0049] According to some preferred embodiments, the raw material tank is equipped with a metering system for quantitative delivery; the raw material tank is also provided with an inlet for the introduction of inert gas (e.g., nitrogen); this inlet is used for the addition of inert gas to prevent air from mixing in, ensuring operational safety, and at the same time, the introduction of inert gas can be used to pressurize and facilitate the introduction of ethylene oxide into the synthesis reactor; the premixing vessel includes a stirred vessel equipped with a temperature control system and a metering system for quantitative mixing and delivery of raw materials (e.g., alkyl glycolate) and synthesis catalyst; the synthesis reactor includes a... The reactor includes a stirring vessel with a material inlet, an air inlet, an exhaust outlet (for connection to a vacuum pump via pipeline), and a temperature control system for mixing materials and controlling the temperature of the reaction; the vacuum distillation vessel includes a stirring vessel equipped with a temperature control system; the vacuum distillation vessel also has, for example, a feeding port for adding a dehydrating agent to reduce the water content of the monomer; the amount of the dehydrating agent is, for example, 0.25~10wt% of the first raw material (glycolic acid and / or methyl glycolate); and / or the monomer collection tank includes a stirring vessel equipped with a temperature control system and a metering system for the sealed storage and quantitative delivery of the monomer.

[0050] According to some preferred embodiments, a monomer storage tank is further provided between the monomer collection tank and the polymerization reactor, and the monomer storage tank and the polymerization reactor are connected in sequence; in this invention, the provision of the monomer storage tank is beneficial to realize the continuous operation of the rectifier; in this invention, for example, the monomer storage tank includes a stirred tank with a temperature control system and a metering system for storing and quantitatively transporting monomers.

[0051] According to some preferred embodiments, the polymerization reactor includes a stirred vessel with a feed port (also referred to as a solid feed port), a feed end, an air inlet (for inert gas to enter), an exhaust port (for connection to a vacuum pump via a pipeline) and a temperature control system. The polymerization reactor also has an auxiliary agent tank containing a catalyst, which is connected to the feed port of the polymerization reactor so that the catalyst enters the polymerization reactor from the feed port.

[0052] It should be noted that all connections involved in this invention are through pipelines, and control valves are installed on the pipelines. The control valves are used to control the flow of materials and the operation at each stage. This invention does not specifically limit the temperature adjustment range of the various temperature control systems involved, for example, it can be 0~300℃.

[0053] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0054] In this invention, a closed continuous system is used with commercially available methyl glycolate and ethylene oxide as reactants. By controlling the reaction temperature and pressure, feeding method, raw material dosage, catalyst type, and reaction conditions, side reactions are suppressed. Multiple vacuum distillations are employed to efficiently purify the reaction product (crude product), enabling large-scale preparation of high-purity poly(p-dioxanone) monomer (purified monomer). The purified monomer is then directly introduced into a polymerization reactor for catalytic polymerization to obtain the target product, poly(p-dioxanone). After polymerization, the material is discharged and the reactor is cleaned by depolymerization at high temperature. No reactor opening or cleaning is required before proceeding to the next round of polymerization. This achieves an operable continuous process with a simple production flow, effectively reducing costs and making it suitable for large-scale production.

[0055] Example 1 This embodiment provides a method for continuous production of poly(p-dioxanone), wherein the method is carried out using an apparatus for continuous production of poly(p-dioxanone), the apparatus being as follows: Figure 2 As shown; the device includes a raw material tank 1, a premixing kettle 2, a synthesis reactor 3, a purification device, a monomer collection tank 6, a polymerization reactor 7, and a depolymerization product collection tank 8; the purification device (using a single-stage vacuum distillation unit) includes a vacuum distillation kettle 4 and a distillation by-product collection tank 5 connected to the vacuum distillation kettle 4.

[0056] The raw material tank is connected to the first feed end of the synthesis reactor via a pipeline, and a control valve is installed on the pipeline between the raw material tank and the synthesis reactor. The raw material tank is also equipped with an inlet for inert gas (nitrogen) (connected to a nitrogen passage) and a metering system. A flow control device is installed on the pipeline connecting the raw material tank and the synthesis reactor. The premixing tank is connected to the second feed end of the synthesis reactor via a pipeline, and a control valve is installed on the pipeline between the premixing tank and the synthesis reactor. The premixing tank includes a stirred tank equipped with a temperature control system and a metering system. A flow control device is installed on the pipeline connecting the premixing tank and the synthesis reactor. The synthesis reactor is connected to a purification device via a pipeline. The reactor includes a vacuum distillation vessel with a feed end connected to it, and a control valve installed on the pipeline between the synthesis reactor and the vacuum distillation vessel. The synthesis reactor includes a stirred vessel with a first feed end, a second feed end, an inlet (for nitrogen gas entry, connected to a nitrogen gas passage), an exhaust port (for connection to a vacuum pump via a pipeline), and a temperature control system. One distillation outlet of the vacuum distillation vessel is connected to a condenser on a distillation by-product collection tank via a secondary pipeline, and a control valve is installed on this secondary pipeline. The other distillation outlet of the vacuum distillation vessel is connected to a condenser on a monomer collection tank via a main pipeline, and a control valve is installed on this main pipeline. The vacuum distillation vessel includes a stirred vessel equipped with a temperature control system. A discharge valve is installed at the lower end of the reactor (this discharge valve can be used to clean the reactor body after multiple rounds of continuous production), and a discharge valve is also installed at the lower end of the distillation by-product collection tank; a monomer collection tank is connected to the feed end of the polymerization reactor via a pipeline, and a control valve is installed on the pipeline between the monomer collection tank and the polymerization reactor; the monomer collection tank includes a stirred tank equipped with a temperature control system and a metering system, and the monomer collection tank is also equipped with an air inlet (for nitrogen gas entry, the air inlet is connected to the nitrogen gas passage); the distillation outlet of the polymerization reactor is connected to the condenser on the depolymerization product collection tank via a pipeline, and a control valve is installed on this pipeline; the vacuum distillation reactor, distillation by-product collection tank, polymerization reactor, and depolymerization product collection tank are described. The lower end is equipped with a discharge valve; the polymerization reactor includes a stirred tank with a feed port, an auxiliary agent tank (the auxiliary agent tank is connected to the feed port of the polymerization reactor), a feed end, an air inlet (for nitrogen to enter, the air inlet is connected to the nitrogen passage), an exhaust port (for connecting to the vacuum pump through a pipeline) and a temperature control system. The temperature control system configured in the polymerization reactor can adjust the temperature of the polymerization reactor after the polymerization reaction is completed, thereby giving the polymerization reactor a depolymerization treatment function to achieve cleaning of the polymerization reactor; the synthesis reactor, the distillation by-product collection tank, the monomer collection tank and the depolymerization product collection tank are respectively connected to the vacuum pump 9 through four independent pipelines, and each independent pipeline is equipped with an independent control valve;Four independent pipelines converge into a vacuum manifold, the end of which is connected to a vacuum pump. A first vacuum control valve is installed at the beginning of the vacuum manifold, and a second vacuum control valve is installed at the end of the manifold before it leads to the vacuum pump. By controlling the opening and closing of each independent control valve, the first vacuum control valve, and the second vacuum control valve, independent or combined vacuuming operations can be achieved for each unit. The distillation by-product collection tank, the monomer collection tank, and the depolymerization product collection tank are respectively connected to the vacuum pump via corresponding condensers and pipelines.

[0057] This device can achieve continuous operation throughout the entire process through automated control.

[0058] This embodiment describes a method for continuous production of poly(p-dioxanone) using the aforementioned apparatus, comprising: Under nitrogen protection, 220 mL of methyl glycolate and 16 g of bis(triphenylphosphine)ammonium chloride were added to the synthesis reactor. After heating to 70°C, 180 g of ethylene oxide was gradually introduced over 4 hours. The pressure inside the synthesis reactor was maintained at 0.1~0.4 MPa. After the addition was completed, the reaction continued for 2 hours. The resulting liquid was purified by a purification device: first, excess ethylene oxide was removed by vacuum distillation at 40°C for 0.5 hours, then the byproduct methanol was removed by vacuum distillation at 70°C for 1 hour, and finally, the pressure was increased to 100°C and reduced for 2 hours to obtain high-purity p-dioxanone (high-purity monomer) with a purity >99%. The monomer yield was 95%, and the monomer was stored in a collection tank for later use. Then, under a nitrogen atmosphere, 59.5 mg of stannous octoate was added to the polymerization reactor, and 300 g of high-purity monomer was introduced. The reaction was carried out at 110°C for 2 hours, and 295 g of poly(p-dioxanone) was discharged, with a yield of 98%. After the polymerization reaction was completed, the product was discharged, and the polymerization reactor was heated to 240°C for vacuum distillation (depolymerization treatment) for 2 hours to remove the depolymerization product. Then, the next round of polymerization was directly carried out, realizing the continuous and efficient production of poly(p-dioxanone). The specific operation of the continuous production equipment for poly(p-dioxanone) is as follows: ① Premix 220mL of methyl glycolate and 16g of bis(triphenylphosphine)ammonium chloride in a premixing vessel to obtain a mixture. Open the control valve on the pipeline connecting the synthesis reactor and the vacuum pump to create a negative pressure inside the synthesis reactor by evacuation. Introduce the mixture from the premixing vessel into the synthesis reactor by controlling the control valve between the premixing vessel and the synthesis reactor. After the introduction is complete, close the control valve between the premixing vessel and the synthesis reactor. Control the control valve and nitrogen passage on the pipeline connecting the synthesis reactor and the vacuum pump to replace the gas in the synthesis reactor with nitrogen. Close the control valve on the pipeline connecting the synthesis reactor and the vacuum pump. Heat the synthesis reactor to 70℃. Control the nitrogen passage corresponding to the raw material tank to ensure that the pressure inside the raw material tank is 0.2MPa higher than the pressure inside the synthesis reactor. Maintain a constant pressure difference and gradually introduce 180g of ethylene oxide into the synthesis reactor over 4 hours, keeping the pressure inside the synthesis reactor between 0.1 and 0.4MPa. After the addition is complete, close the control valve between the raw material tank and the synthesis reactor. Maintain the temperature and pressure inside the synthesis reactor and continue the reaction for 2 hours.

[0059] ② After the reaction is complete, close the nitrogen passage of the synthesis reactor, open the control valve between the vacuum distillation kettle and the distillation by-product collection tank, and open the control valve on the pipeline connecting the distillation by-product collection tank and the vacuum pump. Create a negative pressure in the vacuum distillation kettle and the distillation by-product collection tank by drawing a vacuum. Open the control valve between the synthesis reactor and the vacuum distillation kettle, and pass the synthesized liquid into the vacuum distillation kettle. Heat the vacuum distillation kettle to 40°C and distill under reduced pressure for 0.5 hours to remove excess ethylene oxide. The ethylene oxide is then condensed into the distillation by-product collection tank. Close the control valve between the vacuum distillation kettle and the distillation by-product collection tank, and the control valve on the pipeline connecting the distillation by-product collection tank and the vacuum pump. Open the discharge valve of the distillation by-product collection tank to discharge the ethylene oxide. Close the discharge valve, and open the control valve between the vacuum distillation kettle and the distillation by-product collection tank, and the control valve on the pipeline connecting the distillation by-product collection tank and the vacuum pump. The control valve on the connecting pipeline is used to heat the vacuum distillation kettle to 70°C and distill under reduced pressure for 1 hour to remove the byproduct methanol. The methanol is then condensed into the distillation byproduct collection tank. The control valves between the vacuum distillation kettle and the distillation byproduct collection tank, as well as the control valve on the connecting pipeline between the distillation byproduct collection tank and the vacuum pump, are then closed. The discharge valve of the distillation byproduct collection tank is opened to discharge the byproduct methanol. The control valve on the connecting pipeline between the monomer collection tank and the vacuum pump is opened to create a negative pressure inside the monomer collection tank. The control valve between the vacuum distillation kettle and the monomer collection tank is then opened, and the vacuum distillation kettle is heated to 100°C and distilled under reduced pressure for 2 hours. The methanol is then condensed into the monomer collection tank to obtain high-purity p-dioxanone with a purity >99% and a yield of 95%, approximately 330g. After the vacuum distillation is completed, the control valves between the vacuum distillation kettle and the monomer collection tank, as well as the control valve on the connecting pipeline between the monomer collection tank and the vacuum pump, are closed.

[0060] ③ Open the nitrogen passage of the monomer collection tank to bring the tank to atmospheric pressure. Open the control valve between the polymerization reactor and the depolymerization product collection tank, and the control valve on the pipeline connecting the depolymerization product collection tank and the vacuum pump to bring the polymerization reactor and the depolymerization product collection tank to negative pressure. Open the control valve between the monomer collection tank and the polymerization reactor, and introduce 300g of purified monomer. Close the control valve between the monomer collection tank and the polymerization reactor. Control the nitrogen passage of the polymerization reactor and the control valve between the polymerization reactor and the depolymerization product collection tank to create a nitrogen environment inside the reactor. Close the control valve between the polymerization reactor and the depolymerization product collection tank. Control the addition of 59.5mg of stannous octoate catalyst from the feed port of the tank containing the stannous octoate auxiliary agent. Heat the polymerization reactor to 110℃ and react for 2 hours. After polymerization is complete, open the discharge valve of the polymerization reactor to discharge 295g of poly(p-dioxane), with a yield of 98%. After discharge, close the discharge valve of the polymerization reactor and heat the polymerization reactor to... The polymerization reactor is depolymerized at 240℃. The control valves between the polymerization reactor and the depolymerization product collection tank, as well as the control valve on the pipeline connecting the depolymerization product collection tank and the vacuum pump, are opened. The reactor is then subjected to vacuum distillation (depolymerization treatment) for 2 hours to discharge the depolymerization product, which is then condensed into the depolymerization product collection tank to clean the polymerization reactor. After cleaning, the control valves between the polymerization reactor and the depolymerization product collection tank, as well as the control valve on the pipeline connecting the depolymerization product collection tank and the vacuum pump, are closed. The discharge valve of the depolymerization product collection tank is opened to discharge the depolymerization product, while the polymerization reactor is cooled to 110℃. After discharging the depolymerization product, the discharge valve of the depolymerization product collection tank is closed. The control valves between the polymerization reactor and the depolymerization product collection tank, as well as the control valve on the pipeline connecting the depolymerization product collection tank and the vacuum pump, are opened. A vacuum is created in the polymerization reactor and the depolymerization product collection tank to create negative pressure. 300g of purified monomer is then introduced, and the next round of polymerization production is directly initiated, achieving continuous and efficient production of poly(p-dioxanone).

[0061] Using the apparatus and the same operation described above in this embodiment, continuous production of polydioxanone was carried out in 10 repeated batches, and the yield of polydioxanone in each batch could reach 98%.

[0062] Example 2 Example 2 is basically the same as Example 1, except that: This embodiment employs a method for continuous production of poly(p-dioxanone) using an apparatus for continuous production, including: Under nitrogen protection, 220 mL of methyl glycolate and 16 g of bis(triphenylphosphine)ammonium chloride were added to the synthesis reactor. After heating to 100 °C, 180 g of ethylene oxide was gradually introduced over 4 hours. The pressure inside the synthesis reactor was maintained at 0.1–0.4 MPa. After the addition was complete, the reaction continued for 2 hours. The resulting liquid was purified by a purification device: first, excess ethylene oxide was removed by vacuum distillation at 40 °C for 0.5 hours; then, the byproduct methanol was removed by vacuum distillation at 70 °C for 1 hour; finally, the pressure was increased to 100 °C and reduced for 2 hours to obtain high-purity p-dioxane. Ketone (high-purity monomer), purity >99%, yield 95%, was stored in a monomer collection tank for later use; then, under a nitrogen atmosphere, 59.5 mg of stannous octoate was added to the polymerization reactor, and 300 g of high-purity monomer was introduced. The reaction was carried out at 110 °C for 2 hours, and 295 g of poly(p-dioxanone) was discharged, with a yield of 98%; after the polymerization reaction was completed, the material was discharged and the polymerization reactor was heated to 240 °C. The reactor was then subjected to vacuum distillation (depolymerization treatment) for 2 hours to remove the depolymerization products. Then, the next round of polymerization production was carried out directly, realizing the continuous and efficient production of poly(p-dioxanone).

[0063] Example 3 Example 3 is basically the same as Example 1, except that: This embodiment employs a method for continuous production of poly(p-dioxanone) using an apparatus for continuous production, including: Under nitrogen protection, 220 mL of methyl glycolate and 16 g of bis(triphenylphosphine)ammonium chloride were added to the synthesis reactor. After heating to 70°C, 180 g of ethylene oxide was rapidly introduced into the reactor within 3 minutes. The pressure inside the reactor was maintained at 1-1.4 MPa. After the addition was completed, the reaction continued for 6 hours. The resulting liquid was purified by a purification device: first, excess ethylene oxide was removed by vacuum distillation at 40°C for 0.5 hours, then the byproduct methanol was removed by vacuum distillation at 70°C for 1 hour, and finally, the pressure was increased to 100°C and reduced for 2 hours to obtain high-purity p-ethylene oxide. Cyclohexanone (high-purity monomer), with a purity >99% and a yield of 95%, was stored in a monomer collection tank for later use. Subsequently, under a nitrogen atmosphere, 59.5 mg of stannous octoate was added to the polymerization reactor, and 300 g of high-purity monomer was introduced. The reaction was carried out at 110 °C for 2 hours, and 295 g of poly(p-dioxanone) was discharged, with a yield of 98%. After the polymerization reaction was completed, the material was discharged and the polymerization reactor was heated to 240 °C. The reactor was then subjected to vacuum distillation (depolymerization treatment) for 2 hours to remove the depolymerization products. The next round of polymerization was then carried out directly, realizing the continuous and efficient production of poly(p-dioxanone).

[0064] Example 4 Example 4 is basically the same as Example 1, except that: This embodiment employs a method for continuous production of poly(p-dioxanone) using an apparatus for continuous production, including: Under nitrogen protection, 220 mL of methyl glycolate and 29.9 g of bis(triphenylphosphine)ammonium chloride were added to the synthesis reactor. After heating to 70°C, 180 g of ethylene oxide was gradually introduced over 4 hours. The pressure inside the synthesis reactor was maintained at 0.1–0.4 MPa. After the addition was complete, the reaction continued for 2 hours. The resulting liquid was purified by a purification device: first, excess ethylene oxide was removed by vacuum distillation at 40°C for 0.5 hours; then, the byproduct methanol was removed by vacuum distillation at 70°C for 1 hour; finally, the temperature was raised to 100°C and the pressure was reduced for 2 hours to obtain high-purity p-dioxane. Ketone (high-purity monomer), purity >99%, yield 95%, was stored in a monomer collection tank for later use; then, under a nitrogen atmosphere, 59.5 mg of stannous octoate was added to the polymerization reactor, and 300 g of high-purity monomer was introduced. The reaction was carried out at 110 °C for 2 hours, and 295 g of poly(p-dioxanone) was discharged, with a yield of 98%; after the polymerization reaction was completed, the material was discharged and the polymerization reactor was heated to 240 °C. The reactor was then subjected to vacuum distillation (depolymerization treatment) for 2 hours to remove the depolymerization products. Then, the next round of polymerization production was carried out directly, realizing the continuous and efficient production of poly(p-dioxanone).

[0065] Example 5 Example 5 is basically the same as Example 1, except that: This embodiment employs a method for continuous production of poly(p-dioxanone) using an apparatus for continuous production, including: Under nitrogen protection, 220 mL of methyl glycolate and 16 g of bis(triphenylphosphine)ammonium chloride were added to the synthesis reactor. After heating to 70°C, 180 g of ethylene oxide was gradually introduced over 4 hours. The pressure inside the synthesis reactor was maintained at 0.1–0.4 MPa. After the addition was complete, the reaction continued for 2 hours. The resulting liquid was purified by a purification device: first, excess ethylene oxide was removed by vacuum distillation at 40°C for 0.5 hours; then, the byproduct methanol was removed by vacuum distillation at 70°C for 1 hour; finally, the temperature was raised to 100°C and the pressure was reduced for 2 hours to obtain high-purity p-dioxane. Ketone (high-purity monomer), with a purity >99% and a yield of 95%, was stored in a monomer collection tank for later use. Subsequently, under a nitrogen atmosphere, 0.79g of lanthanum isopropoxide was added to the polymerization reactor, and 300g of high-purity monomer was introduced. The reaction was carried out at 110℃ for 2 hours, and 295g of poly(p-dioxanone) was discharged, with a yield of 98%. After the polymerization reaction was completed, the material was discharged and the polymerization reactor was heated to 240℃. The reactor was then subjected to vacuum distillation (depolymerization treatment) for 2 hours to remove the depolymerization products. The next round of polymerization production was then carried out directly, realizing the continuous and efficient production of poly(p-dioxanone).

[0066] Example 6 Example 6 is basically the same as Example 1, except that: This embodiment employs a method for continuous production of poly(p-dioxanone) using an apparatus for continuous production, including: Under nitrogen protection, 220 mL of methyl glycolate and 16 g of bis(triphenylphosphine)ammonium chloride were added to the synthesis reactor. After heating to 70°C, 180 g of ethylene oxide was gradually introduced over 4 hours. The pressure inside the synthesis reactor was maintained at 0.1~0.4 MPa. After the addition was completed, the reaction continued for 2 hours. The resulting liquid was purified by a purification device: first, excess ethylene oxide was removed by vacuum distillation at 40°C for 0.5 hours, then the byproduct methanol was removed by vacuum distillation at 70°C for 1 hour, and then the pressure was increased to 100°C and reduced for 2 hours to obtain high-purity p-dioxanone (high-purity monomer) with a purity >99% and a yield of 95%. The product was then stored in a container. The solid collection tank is kept for later use; then, under a nitrogen atmosphere, 59.5 mg of stannous octoate is added to the polymerization reactor, 300 g of high-purity monomer is introduced, and the reaction is carried out at 110 °C for 2 hours. 295 g of poly(p-dioxane) is discharged, with a yield of 98%; after the polymerization reaction is completed, 0.04 g of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (depolymerization catalyst) is added to the polymerization reactor after discharge, and the polymerization reactor is heated to 140 °C and subjected to vacuum distillation (depolymerization treatment) for 2 hours to discharge the depolymerization product. Then, the next round of polymerization production is carried out directly to achieve continuous and efficient production of poly(p-dioxane).

[0067] Example 7 Example 7 is basically the same as Example 1, except that: This embodiment employs a method for continuous production of poly(p-dioxanone) using an apparatus for continuous production, including: Under nitrogen protection, 220 mL of methyl glycolate and 8.9 g of ferric chloride were added to the synthesis reactor. After heating to 70°C, 180 g of ethylene oxide was gradually introduced over 4 hours. The pressure inside the synthesis reactor was maintained at 0.1~0.4 MPa. After the addition was complete, the reaction continued for 2 hours. The resulting liquid was purified by a purification device: first, excess ethylene oxide was removed by vacuum distillation at 40°C for 0.5 hours, then the byproduct methanol was removed by vacuum distillation at 70°C for 1 hour, and finally, the temperature was raised to 100°C and the pressure was reduced for 2 hours to obtain high-purity p-dioxanone (high purity). Monomers with a purity >99% and a yield of 65% were stored in a monomer collection tank for later use. Subsequently, under a nitrogen atmosphere, 59.5 mg of stannous octoate was added to the polymerization reactor, and 100 g of high-purity monomer was introduced. The reaction was carried out at 110 °C for 2 hours, and 98 g of poly(p-dioxanone) was discharged, with a yield of 98%. After the polymerization reaction was completed, the material was discharged and the polymerization reactor was heated to 240 °C. The reactor was then subjected to vacuum distillation (depolymerization treatment) for 2 hours to remove the depolymerization products. The next round of polymerization production was then carried out directly, realizing the continuous and efficient production of poly(p-dioxanone).

[0068] Example 8 Example 8 is basically the same as Example 1, except that: This embodiment employs a method for continuous production of poly(p-dioxanone) using an apparatus for continuous production, including: Under nitrogen protection, 220 mL of methyl glycolate and 8.3 g of tetrabutylammonium chloride were added to a synthesis reactor. After heating to 70°C, 180 g of ethylene oxide was gradually introduced over 4 hours. The pressure inside the synthesis reactor was maintained at 0.1–0.4 MPa. After the addition was complete, the reaction continued for 2 hours. The resulting liquid was purified using a purification device: first, excess ethylene oxide was removed by vacuum distillation at 40°C for 0.5 hours; then, the byproduct methanol was removed by vacuum distillation at 70°C for 1 hour; finally, the temperature was raised to 100°C and the pressure was reduced for 2 hours to obtain high-purity p-dioxanone (high-purity p-dioxanone). The monomer (pure monomer), with a purity >99% and a yield of 95%, is stored in a monomer collection tank for later use. Subsequently, under a nitrogen atmosphere, 59.5 mg of stannous octoate is added to the polymerization reactor, and 300 g of high-purity monomer is introduced. The reaction is carried out at 110 °C for 2 hours, and 295 g of poly(p-dioxanone) is discharged, with a yield of 98%. After the polymerization reaction is completed, the material is discharged and the polymerization reactor is heated to 240 °C. The reactor is then subjected to vacuum distillation (depolymerization treatment) for 2 hours to remove the depolymerization product. Then, the next round of polymerization production is carried out directly, realizing the continuous and efficient production of poly(p-dioxanone).

[0069] Example 9 Example 9 is basically the same as Example 1, except that: This embodiment employs a method for continuous production of poly(p-dioxanone) using an apparatus for continuous production, including: Under nitrogen protection, 1000 mL of methyl glycolate and 38 g of bis(triphenylphosphine)ammonium chloride were added to the synthesis reactor. After heating to 70°C, 860 g of ethylene oxide was gradually introduced over 4 hours. The pressure inside the synthesis reactor was maintained at 0.1~0.6 MPa. After the addition was completed, the reaction continued for 2 hours. The resulting liquid was purified by a purification device: first, excess ethylene oxide was removed by vacuum distillation at 40°C for 0.5 hours, then the byproduct methanol was removed by vacuum distillation at 70°C for 2 hours, and finally, the pressure was increased to 100°C and vacuum distilled for 3 hours to obtain high-purity p-dioxane. Ketone (high-purity monomer), purity >99%, yield 95%, was stored in a monomer collection tank for later use; then, under a nitrogen atmosphere, 59.5 mg of stannous octoate was added to the polymerization reactor, and 300 g of high-purity monomer was introduced. The reaction was carried out at 110 °C for 2 hours, and 295 g of poly(p-dioxanone) was discharged, with a yield of 98%; after the polymerization reaction was completed, the material was discharged and the polymerization reactor was heated to 240 °C. The reactor was then subjected to vacuum distillation (depolymerization treatment) for 2 hours to remove the depolymerization products. Then, the next round of polymerization production was carried out directly, realizing the continuous and efficient production of poly(p-dioxanone).

[0070] In the description of this invention, it should also be noted that, unless otherwise explicitly specified and limited, the term "connection" should be interpreted broadly, for example, it can refer to direct connection or indirect connection through an intermediate medium. Those skilled in the art can understand the specific meaning of this term in this invention depending on the specific circumstances.

[0071] The parts of this invention not described in detail are techniques known to those skilled in the art.

[0072] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for the continuous production of poly(p-dioxanone) characterized in that, The method comprises the following steps: (1) Pre-mixing glycolic acid and / or glycolic acid derivatives with a ring-forming catalyst to obtain a mixture, and feeding the mixture and ethylene oxide into a synthesis reactor to perform a ring-forming reaction to obtain a reaction product; (2) Separating and purifying the reaction product to obtain a purified monomer, feeding the purified monomer into a polymerization reactor, and adding a polymerization catalyst into the polymerization reactor to perform a polymerization reaction; (3) After the polymerization reaction is completed, discharging the polydioxanone obtained by the polymerization reaction, and performing depolymerization treatment on the residual material in the polymerization reactor, discharging the depolymerization product generated in the depolymerization treatment, and performing the next round of polymerization production.

2. The method of claim 1, wherein: the ring-forming reaction is performed under inert gas protection; the ring-forming reaction is performed at a pressure of 0.1-5 MPa, a temperature of 0-100°C, and a time of 0.5-12 h; preferably, the ring-forming reaction is performed at a pressure of 0.1-3 MPa, a temperature of 70-100°C, and a time of 2-6 h. The glycolic acid derivative is an alkyl glycolate, and the structure of the alkyl glycolate is shown in the following formula I: Formula I In formula I, R is C1-C6 alkyl or C3-C6 cycloalkyl; preferably, the alkyl glycolate is methyl glycolate, and the ring-forming catalyst is bis(triphenylphosphine)ammonium chloride and / or tetrabutylammonium salt.

3. The method of claim 1, wherein:

4. The method of claim 1, wherein: the molar ratio of the amount of the glycolic acid and / or the glycolic acid derivative to the amount of the ring-forming catalyst is 1:0.0001-1:0.05, preferably 1:0.002-1:0.02; the molar ratio of the amount of the glycolic acid and / or the glycolic acid derivative to the amount of the ethylene oxide is 5:1-1:5, preferably 1:1.1-1:2; and / or the ethylene oxide is added in one of the following ways: added at one time before the ring-forming reaction or continuously added during the ring-forming reaction; preferably, the ethylene oxide is continuously added during the ring-forming reaction, and the addition time is 1-4 h.

5. The method of claim 1, wherein: the separation and purification is one or more of filtration, washing, distillation, rectification, and crystallization; preferably, the separation and purification is reduced-pressure distillation and / or reduced-pressure rectification; the polymerization reaction is performed under inert gas protection; and / or the temperature of the polymerization reaction is 40-160°C, preferably 80-140°C, and the time of the polymerization reaction is 1-3 h.

6. The method of claim 1, wherein: the temperature in the polymerization reactor is adjusted to 100-300°C to perform depolymerization treatment on the residual material in the polymerization reactor; the temperature of the depolymerization treatment is 100-300°C, and the time of the depolymerization treatment is 1-3 h. the ring-forming catalyst is selected from the group consisting of iron trichloride, copper tetrafluoroborate, aluminum triflate, bismuth triflate, 1,8 diazabicyclo[5.4.0]undec 7 one, tetramethylammonium salt, tetraethylammonium salt, tetrabutylammonium salt, phosphacene ligand P1-t-Bu, phosphacene ligand P2-t-Bu, phosphacene ligand P4-t-Bu, 2,4,6-tris[tris(dimethylamino)iminophosphorane]-1,3,5-triazine, 2,4,6-tris[tris(1-pyrrolidinyl)-iminophosphorane]-1,3,5-triazine, cyclotriphosphazene base, bis(triphenylphosphorane)iminophosphonium salt, tetraphenylphosphonium salt, tris[tris(dimethylamino)iminophosphorane]phosphonium salt, tetra[tris(dimethylamino)iminophosphorane]phosphonium salt.

7. The method of claim 1, wherein: the polymerization catalyst is one or more of a tin catalyst, an aluminum catalyst, a transition metal catalyst, a rare earth catalyst, an organic base catalyst, and an enzyme catalyst; and / or ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ The molar ratio of the polymerization catalyst to the purified monomer is 1:100-1:10000, preferably 1:500-1:5000.

8. The method of claim 1, wherein: When the depolymerization treatment is performed, a depolymerization catalyst is further added, and preferably the depolymerization catalyst is selected from one or more of stannous octoate, zinc oxide, magnesium oxide, zinc acetate, manganese acetate, and 1,5,7-triazabicyclo[4.4.0]dec-5-ene; In step (3), the depolymerization product generated in the depolymerization treatment is discharged by reduced pressure distillation and / or through a discharge valve; and / or The number average molecular weight of the poly-p-dioxanone is 800-500000 g / mol, and the viscosity average molecular weight is 1000-800000 g / mol.

9. The method of claim 1, wherein, The method is performed using a device for continuous production of poly-p-dioxanone, the device comprising: a raw material tank, a premixing kettle, a synthesis reaction kettle, a purification device, a monomer collection tank, a polymerization reaction kettle, and a depolymerization product collection tank; The raw material tank and the premixing kettle are in communication with the feed end of the synthesis reaction kettle, and the synthesis reaction kettle, the purification device, the monomer collection tank, the polymerization reaction kettle, and the depolymerization product collection tank are in communication in sequence, forming a continuous closed system; The purification device comprises a primary reduced pressure distillation unit or a plurality of reduced pressure distillation units connected in series, and each reduced pressure distillation unit comprises a reduced pressure distillation kettle and a distillation byproduct collection tank in communication with the reduced pressure distillation kettle; preferably, the temperature of the reduced pressure distillation kettle is 25-150°C; The polymerization reaction kettle is provided with a temperature control system, which can impart the polymerization reaction kettle with a depolymerization treatment function by adjusting the temperature of the polymerization reaction kettle after the polymerization reaction is completed, so as to clean the polymerization reaction kettle.

10. The method of claim 9, wherein: The purification device comprises a primary reduced pressure distillation unit; The reduced pressure distillation kettle is in communication with the synthesis reaction kettle, and the reduced pressure distillation kettle is also in communication with the monomer collection tank through a condenser; When the purification device comprises a primary reduced pressure distillation unit, the separation and purification is 25-50°C reduced pressure distillation, 50-90°C reduced pressure distillation, and 100-150°C reduced pressure distillation in sequence.

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