Classifications

• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
  • C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
  • C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
  • C08G63/08—Lactones or lactides
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
  • C08G63/78—Preparation processes
• • C—CHEMISTRY; METALLURGY
  • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
  • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
  • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
  • C08G63/78—Preparation processes
  • C08G63/82—Preparation processes characterised by the catalyst used
  • C08G63/823—Preparation processes characterised by the catalyst used for the preparation of polylactones or polylactides

Definitions

• the invention belongs to the field of biomedical materials science, and particularly relates to a process for catalytic synthesis of medical high performance biodegradable polymers.
• PLA Polylactic acid
• Implanted/implantable absorbable hard tissue repair alternative materials (such as fracture internal fixation splint, bone Screws, meniscus, pipe support materials, etc.).
• the application involving the above items III., IV. requires not only the polylactic acid (usually poly-L-lactic acid, PLLA) used to have excellent biocompatibility and biodegradability, but also has (1) high molecular weight (weight average molecular weight Mw) ⁇ 4.0 ⁇ 10 5 ); (2) excellent thermal properties (melting point Tm ⁇ 173 ° C); (3) excellent crystallinity (crystallinity Xc ⁇ 60%); (4) does not contain any colored impurities.
• Poly L-lactic acid conforming to the above four performance indexes is referred to as high performance high molecular weight poly-L-lactic acid.
• poly-L-lactic acid since materials used in the fields of III. and IV. are embedded/implanted for a long time, the material should not contain any cytotoxic heavy metals and other toxic components to prevent malignant lesions of tissues.
• stannous octoate chemical name: stannous 2-ethylhexanoate
• the cytotoxic tin salt cannot be completely removed from the product polymer, so it is synthesized.
• Poly L-lactic acid is a safety hazard when used as a long-term implantable/implantable absorbable material.
• the synthesis of highly biosafety, high performance, high molecular weight poly L-lactic acid is a challenging research topic in the field of biomedical degradation materials.
• the inventors of the present application have recently successfully developed a new process for the catalytic synthesis of highly biosafety, high performance, high molecular weight poly-L-lactic acid based on the long-term research work on bioorganic ruthenium catalyst synthesis of biodegradable polymers.
• the new process introduced by the present invention has broad and important application prospects in the field of biomedical materials science.
• a new process for the synthesis of high performance, high molecular weight poly-L-lactic acid (h-PLLA).
• the process adopts an organic bismuth (BG) compound formed by a metabolic process in the human body as a catalyst, and a non-toxic acid salt of a trace metal necessary for the human body is an efficient, highly biosafety two-component catalytic system composed of an activator (Act) (BG- Act); ring-opening polymerization of L-lactide (LLA) by bulk polymerization.
• BG- Act activator
• LSA L-lactide
• BG bioorganic ruthenium main catalyst
• the monomer LLA, the catalyst (BG) and the activator (Act) were charged into the polymerization reactor, and the air in the polymerization vessel was driven off by three "vacuum-nitrogen-filled" cycle operations, and ring-opening polymerization of LLA was carried out by bulk polymerization.
• the conditional control of the polymerization is carried out by a two-stage method.
• the high-performance high molecular weight poly L finally obtained by carrying out the polymerization reaction under the conditions of the second-stage polymerization reaction - Lactic acid (h-PLLA) Mw is 4.0-5.5 x 10 5 .
• the high performance high molecular weight poly-L-lactic acid product synthesized by the invention has the following properties:
• the Mw of the polymer can be controlled and synthesized in the range of 4.0-5.5 ⁇ 10 5 according to the practical application requirements.
• the polymerization catalyst system is a non-toxic (non-cytotoxic), two-component catalytic system that can be absorbed and metabolized by organisms, including: the main catalyst (the arginine metabolism and the energy release/energy storage process in human body) One of the bioorganic bismuth compounds arginine, thioglycolic acid, creatine, creatinine or creatine phosphate) and an activator (one of the essential non-toxic salts of potassium, iron, zinc and calcium necessary for human body);
• the catalytic system has high catalytic ring-opening polymerization activity, and the amount of the catalyst and the activator is 0.001-0.05 wt% of the weight of the monomer LLA;
• the non-toxic acid salt is carbonate, acetate, lactate, glycolate.
• the high-performance high-molecular-weight poly-L-lactic acid product synthesized by the invention has been proved to be non-cytotoxic by the national authorized identification institution.
• the two-component catalytic system (main catalyst + activator) used in the present invention is a non-cytotoxic "green" catalytic system
• the synthesized poly-L-lactic acid product does not contain unreacted monomer (L-lactide), does not contain any cytotoxic components, and is a highly biosafety "green” biodegradable polymer;
• High-performance high-molecular-weight poly-L-lactic acid products can be controlled and synthesized according to application requirements.
• the monomer LLA, the catalyst and the activator are added to the polymerization reactor, and the catalyst and the activator are used in an amount of 0.001-0.05 wt% of the weight of the monomer LLA.
• the three-stage "vacuum-nitrogen-filled" cycle operation is used to drive out the polymerization vessel. Air, ring-opening polymerization of LLA by bulk polymerization.
• the two-stage polymerization reaction was carried out under -0.3 torr conditions for 25-60 h, and the finally obtained poly-L-lactic acid (h-PLLA) Mw was 4.0-5.5 ⁇ 10 5 .

Landscapes

• Chemical & Material Sciences (AREA)
• Health & Medical Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Medicinal Chemistry (AREA)
• Polymers & Plastics (AREA)
• Organic Chemistry (AREA)
• Polyesters Or Polycarbonates (AREA)
• Biological Depolymerization Polymers (AREA)

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Citations (6)

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• 2014
  • 2014-12-12 CN CN201410765621.9A patent/CN104448261B/zh not_active Expired - Fee Related
• 2015
  • 2015-06-11 JP JP2016567120A patent/JP6343031B2/ja not_active Expired - Fee Related
  • 2015-06-11 WO PCT/CN2015/081253 patent/WO2016090878A1/zh not_active Ceased
  • 2015-09-14 US US14/854,009 patent/US9845377B2/en not_active Expired - Fee Related

Patent Citations (6)

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