Search

CN-121991022-A - Method for recrystallizing p-dioxanone

CN121991022ACN 121991022 ACN121991022 ACN 121991022ACN-121991022-A

Abstract

The invention provides a method for recrystallizing dioxanone, which comprises the steps of (1) vacuumizing a coarse product of the dioxanone at a certain temperature to obtain a mixture of PDO crystals and liquid, heating the separated PDO crystals at normal pressure to sweat, separating the PDO crystals again to serve as seed crystals for recrystallization, (2) mixing aliphatic ester, liquid alkane and the dioxanone, cooling the mixed liquid to a certain temperature, adding the seed crystals prepared in the step (1), carrying out primary constant temperature crystallization, cooling the crystallization liquid to carry out secondary constant temperature crystallization, separating the PDO crystals, (4) cooling the separated PDO crystals and the aliphatic ester, washing the PDO crystals with low-temperature aliphatic ester, and (5) carrying out reduced pressure distillation on the washed PDO crystals to obtain a high-purity dioxanone product. The invention has good purification effect and yield of the paradioxanone, the purity of the paradioxanone in the purified product is more than 99.9 percent, and the mass yield is more than 60 percent.

Inventors

  • LI ZEZHUANG
  • LIU JINGWEI
  • XU JUN
  • YANG LIHUA
  • MA ZHONGLIN
  • ZHAO JUAN

Assignees

  • 中国石油化工股份有限公司
  • 中国石化扬子石油化工有限公司

Dates

Publication Date
20260508
Application Date
20241108

Claims (13)

  1. 1. A method for recrystallizing dioxanone, which is characterized by comprising the following steps: (1) Vacuumizing the coarse product of the paradioxanone at a certain temperature to obtain a mixture of paradioxanone crystals and liquid, heating the separated paradioxanone crystals to a certain temperature under normal pressure to perform sweating, and separating the paradioxanone crystals again to serve as seed crystals for recrystallization; (2) Mixing low boiling point aliphatic ester, low boiling point liquid alkane and paradioxanone crude product in proportion, cooling the mixed solution to a certain temperature, adding the seed crystal prepared in the step (1), and carrying out primary constant temperature crystallization; (3) Slowly cooling the crystallization liquid in the step (2) to a certain temperature, performing secondary constant-temperature crystallization, and then separating the paradioxanone crystals; (4) Cooling the paradioxanone crystals separated in the step (3) and the aliphatic ester in the step (2) to a certain temperature, and cleaning the paradioxanone crystals by using low-temperature aliphatic ester; (5) And (3) distilling the washed paradioxanone crystal under reduced pressure to obtain a paradioxanone product with high purity.
  2. 2. The method for recrystallizing p-dioxanone according to claim 1, wherein in the step (1), the purity of the crude p-dioxanone is 98.2-99.7%.
  3. 3. The method for recrystallizing p-dioxanone according to claim 1, wherein in the step (1), the vacuumizing temperature is 20-26 ℃ and the vacuumizing degree is 10-50 mbar.
  4. 4. The method for recrystallizing p-dioxanone according to claim 1, wherein in the step (1), the sweating temperature is 27-32 ℃ and the sweating time is 0.5-1.5 h.
  5. 5. A method for recrystallizing p-dioxanone according to claim 1, wherein in the step (2), the low boiling point aliphatic ester is at least one of methyl formate, ethyl formate, propyl formate, methyl acetate, ethyl acetate and methyl propionate.
  6. 6. The method for recrystallizing p-dioxanone according to claim 1, wherein in the step (2), the low boiling point liquid alkane is at least one of C5-C7 alkanes.
  7. 7. The method for recrystallizing p-dioxanone according to claim 1, wherein in the step (2), the mass ratio of the aliphatic ester, the liquid alkane and the crude p-dioxanone is 0.4-0.8:0.2-0.5:1, and the mass ratio of the seed crystal to the crude p-dioxanone is 0.001-0.005:1.
  8. 8. The method for recrystallizing p-dioxanone according to claim 1, wherein in the step (2), the primary constant temperature crystallization temperature is 5-13 ℃ and the constant temperature crystallization time is 1-4 h.
  9. 9. The method for recrystallizing p-dioxanone according to claim 1, wherein in the step (3), the cooling rate of the crystallization liquid is 1-5 ℃ per hour.
  10. 10. The method for recrystallizing p-dioxanone according to claim 1, wherein in the step (3), the secondary constant temperature crystallization temperature is-10 to-5 ℃, and the constant temperature crystallization time is 0.5 to 3 hours.
  11. 11. The method for recrystallizing p-dioxanone according to claim 1, wherein in the step (4), the temperature of the crystals and the aliphatic ester is reduced to-20 to-13 ℃.
  12. 12. The method for recrystallizing p-dioxanone according to claim 1, wherein in the step (4), the mass ratio of the aliphatic ester to the p-dioxanone crystals is 0.1-0.3:1.
  13. 13. The method for recrystallizing p-dioxanone according to claim 1, wherein in the step (5), the temperature of reduced pressure distillation is 60-90 ℃, the vacuum degree is 5-30 mbar, and the distillation time is 3-6 h.

Description

Method for recrystallizing p-dioxanone Technical Field The invention relates to the technical field of organic matter purification, in particular to a method for recrystallizing p-dioxanone. Background The p-dioxanone is mainly used for polymerization to prepare high molecular weight polydioxanone. Polydioxanone belongs to an alpha-polyester polymer, and the synthesis process of polydioxanone is widely applied to bioabsorbable surgical sutures, and further partially replaces PGA and PLA as surgical suture materials, which are obtained in 1979 and approved by the United states Food and Drug Administration (FDA). In the last 70 s, ethicon corporation of the united states has successfully prepared degradable surgical sutures from polydioxanone under the PDS trade name. Compared with the surgical suture Dexon produced by taking PGA as a raw material and the surgical suture Vicryl produced by taking glycolide and lactide copolymer (PLGA) as raw materials, the PDS has the advantage of being capable of preparing a monofilament suture due to the excellent toughness, and has the characteristics of high retention rate of tensile strength and knotting strength in the degradation process. In addition to successful application to surgical sutures, polydioxanone is also used in orthopedic fixation materials, tissue repair materials, cell scaffolds, drug carriers, and the like. To obtain high molecular weight polydioxanone requires very high purity of the polydioxanone monomer, typically greater than 99.9% for the polydioxanone. The crude product of the paradioxanone is purified by adopting a rectification process, and a product with the purity of more than 99.9 percent is difficult to obtain. The product obtained in the rectification section is repeatedly distilled under reduced pressure, and distilled fractions in a certain boiling range are collected under a certain vacuum degree, so that although the product with the purity of more than 99.9 percent can be obtained, the yield is very low, and meanwhile, impurities with the boiling point close to that of the paradioxanone are difficult to remove by a distillation method. European patent EP0617029A1 discloses a process for purifying p-dioxanone by recrystallization, but requires two recrystallizations at-20 ℃ or even lower temperatures, which is inconvenient to operate and gives low yields. Disclosure of Invention The invention aims to provide a method for recrystallizing p-dioxanone, which is used for purifying the p-dioxanone, meets the requirements for preparing the poly-p-dioxanone and has higher purification yield. The technical scheme of the invention is as follows: the invention provides a method for recrystallizing p-dioxanone, which comprises the following steps: (1) Vacuumizing the coarse product of the paradioxanone at a certain temperature to obtain a mixture of paradioxanone crystals and liquid, heating the separated paradioxanone crystals to a certain temperature under normal pressure to perform sweating, and separating the paradioxanone crystals again to serve as seed crystals for recrystallization; (2) Mixing low boiling point aliphatic ester, low boiling point liquid alkane and paradioxanone crude product in proportion, cooling the mixed solution to a certain temperature, adding the seed crystal prepared in the step (1), and carrying out primary constant temperature crystallization; (3) Slowly cooling the crystallization liquid in the step (2) to a certain temperature, performing secondary constant-temperature crystallization, and then separating the paradioxanone crystals; (4) Cooling the paradioxanone crystals separated in the step (3) and the aliphatic ester in the step (2) to a certain temperature, and cleaning the paradioxanone crystals by using low-temperature aliphatic ester; (5) And (3) carrying out reduced pressure distillation on the cleaned paradioxanone crystals to obtain a paradioxanone product with high purity. Preferably, the purity of the crude product of the paradioxanone in the step (1) is 98.2-99.7%, and when the purity of the crude product of the paradioxanone is less than 98.2%, the paradioxanone seed crystal with the purity of more than 99.8% cannot be obtained in the step (1), and the paradioxanone product with the purity of more than 99.9% cannot be obtained in the steps (1) - (5). In the preferred step (1), the vacuumizing temperature is 20-26 ℃, the vacuumizing degree is 10-50 mbar, and when the vacuumizing condition does not meet the preferred condition, the p-dioxanone seed crystal with the purity of more than 99.8% cannot be obtained through the step (1). In the preferred step (1), the sweating temperature is 27-32 ℃ and the sweating time is 0.5-1.5 h. When the conditions of sweating do not meet the preferred conditions, seeds of p-dioxanone having a purity of more than 99.8% cannot be obtained by the step (1). Preferably, the low-boiling aliphatic ester in the step (2) is at least one of methyl formate, ethyl formate, propy