WO2009087910A1 - Procédé de fabrication de polymère biodégradable - Google Patents

Procédé de fabrication de polymère biodégradable Download PDF

Info

Publication number
WO2009087910A1
WO2009087910A1 PCT/JP2008/073584 JP2008073584W WO2009087910A1 WO 2009087910 A1 WO2009087910 A1 WO 2009087910A1 JP 2008073584 W JP2008073584 W JP 2008073584W WO 2009087910 A1 WO2009087910 A1 WO 2009087910A1
Authority
WO
WIPO (PCT)
Prior art keywords
acid
trifunctional
polymer
group
catalyst
Prior art date
Application number
PCT/JP2008/073584
Other languages
English (en)
Japanese (ja)
Inventor
Atsushi Abiko
Tatsuya Oka
Hisako Iwahashi
Original Assignee
National University Corporation Kyoto Institute Of Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by National University Corporation Kyoto Institute Of Technology filed Critical National University Corporation Kyoto Institute Of Technology
Priority to JP2009548886A priority Critical patent/JPWO2009087910A1/ja
Publication of WO2009087910A1 publication Critical patent/WO2009087910A1/fr

Links

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
    • C08G63/78—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 present invention relates to a method of producing a biodegradable polymer, and more particularly to a method of producing a biodegradable polymer consisting of poly (hydroxy carboxylic acid).
  • Poly (hydroxycarboxylic acid) represented by poly-L-lactic acid is excellent in mechanical properties, physical properties and chemical properties and is decomposed in the natural environment and is finally decomposed by water and carbonate by microorganisms. It is a biodegradable polymer that has the biodegradable function of becoming a gas, and has recently been attracting attention in various fields such as medical materials and general-purpose resin substitutes, and it is expected that its demand will be greatly expanded in the future There is.
  • poly-L-lactic acid is synthesized by ring-opening polymerization (lactide method) of L-lactide, which is a cyclic diester monomer of lactic acid, or direct dehydration polycondensation of lactic acid, as shown by the following reaction formula.
  • poly-L-lactic acid obtained by these methods is a linear polyester, and at present, satisfactory rheological properties are not obtained in melt molding where high strength and elasticity are required for the melt.
  • a branched structure or a three-dimensional crosslinked structure can be imparted to the poly (hydroxycarboxylic acid), it is possible to impart high strength and elasticity to the melt. Therefore, the method of making poly (hydroxy carboxylic acid) into a branched structure, or using a monomer having a branched structure as a crosslinking component, react the terminal reactive groups of branched chains with each other to crosslink and introduce a three-dimensional crosslinked structure. A method has been proposed.
  • a polyhydroxyl compound having at least 4 hydroxyl groups is mixed with lactic acid, and the resulting mixture is heated under reduced pressure in the absence of a catalyst to remove water to obtain low molecular weight poly (lactic acid), Then, there is proposed a method of heating the poly (lactic acid) under reduced pressure in the presence of a catalyst and subjecting it directly to polycondensation to obtain a poly (lactic acid) having a star-shaped branched structure having a weight average molecular weight of 30,000 or more (Patent Document 1). In this method, antimony oxide is used as a catalyst for the polycondensation reaction of lactic acid.
  • Patent Document 2 There is also proposed a method in which an aliphatic polyhydric alcohol, an aliphatic polybasic acid and a hydroxycarboxylic acid are directly condensation-reacted in a reaction mixture containing an organic solvent (Patent Document 2).
  • a catalyst may or may not be used, and when it is used, the metal of Periodic Table II, III, IV, V, its oxide or its salt can be used as the catalyst Have been described.
  • a method has been proposed in which a low molecular weight polyester prepolymer is formed from a hydroxy acid monomer, and the prepolymer is copolymerized with a monomer that reacts with the terminal group to form a high molecular weight polymer (Patent Document 3) .
  • an alkyl or alkoxy compound of tin or titanium is used as a catalyst for the polycondensation reaction of lactic acid.
  • Japanese Patent Application Laid-Open No. 6-313032 Japanese Patent Application Laid-Open No. 7-228675 Japanese Patent Application Publication No. 11-503185 Tadeusz Biela, Andrzei Duda, Stanislaw Penczek. Macromolecules, 2006, 39, 3710-3713
  • the ring-opening polymerization method generally has a problem that the number of steps is large and the manufacturing process becomes complicated as compared with the direct dehydration polycondensation method. Further, in the methods of Patent Documents 1 to 3, there is a problem that complete removal of the catalyst is difficult because the catalyst activity is low and a metal-based catalyst is used, and the manufacturing process becomes complicated.
  • this invention solved the said subject, and it aimed at providing the manufacturing method of a novel biodegradable polymer which can simplify a manufacturing process and can improve a manufacturing efficiency.
  • the method for producing a biodegradable polymer according to the present invention comprises: component A comprising a bifunctional hydroxycarboxylic acid, a trifunctional or higher carboxylic acid having three or more carboxyl groups in the molecule, a trifunctional or higher monohydroxycarboxylic acid, And it is characterized by carrying out direct dehydration polycondensation with any one B component selected from the group which consists of polyhydroxy polycarboxylic acid in presence of an organic onium salt catalyst.
  • the biodegradable polymer obtained by the above-mentioned production method is a branched polymer or a crosslinked polymer.
  • a trifunctional or higher functional carboxylic acid is used as component B, a star-shaped branched polymer having a carboxyl group at the end can be obtained. That is, the trifunctional or higher functional carboxylic acid constitutes a core component having at least three branch points, and the bifunctional hydroxycarboxylic acid constitutes a polymer chain which becomes a large number of branch components extending radially from the branch point of the core component.
  • a dendritic or comb-shaped hyperbranched polymer having a carboxyl group at the end can be obtained. That is, the bifunctional hydroxycarboxylic acid constitutes a polymer chain to be a main chain component, and the trifunctional or higher functional monohydroxycarboxylic acid constitutes a branched component having at least two branch points.
  • a star-branched polymer refers to a branched polymer having a core component and a large number of branch components extending radially from the branch point of the core component
  • a multi-branched polymer refers to a main chain component
  • polyhydroxypolycarboxylic acid When polyhydroxypolycarboxylic acid is used as component B, a three-dimensionally crosslinked crosslinked polymer having a bifunctional hydroxycarboxylic acid as a main chain component and polyhydroxypolycarboxylic acid as a crosslinking component is obtained. .
  • a polymer having a three-dimensional crosslinked structure is referred to as a network polymer.
  • polyhydroxypolycarboxylic acid refers to a compound having two or more hydroxyl groups and two or more carboxyl groups in the molecule.
  • a biodegradable polymer having a branched structure or a network structure can be synthesized by using an organic onium salt catalyst.
  • the organic onium salt catalyst has higher activity than conventional catalysts. Thereby, the manufacturing process can be simplified and the manufacturing efficiency can be improved.
  • the organic onium salt catalyst used in the present invention can be reused, cost reduction and waste reduction can be achieved.
  • the catalyst used in the present invention is stable to water, a commercially available aqueous solution of lactic acid or glycolic acid can be used as it is. This is advantageous in the sense that a uniform reaction site can be secured at the initial stage of the reaction since the trifunctional or higher functional (mono) hydroxycarboxylic acid usually has no solubility other than water.
  • the biodegradable polymer obtained by the present invention has a branched structure or a network structure, can impart high strength and elasticity to the melt, and has desired rheological properties required for melt molding. It can be granted.
  • Embodiment 1 The method for producing a biodegradable polymer according to the present embodiment is a trifunctional or higher carboxylic acid having three or more carboxyl groups in the molecule, or a monohydroxyl or trifunctional or higher monofunctional hydroxy group. It is characterized in that the component B consisting of a carboxylic acid is directly dehydrated and polycondensed in the presence of an organic onium salt catalyst.
  • the trifunctional or higher carboxylic acid constitutes a core component having at least three branch points
  • the functional hydroxycarboxylic acid constitutes a polymer chain which becomes a number of branch components extending radially from the branch point of the core component.
  • the bifunctional hydroxycarboxylic acid constitutes a polymer chain to be a main chain component
  • the trifunctional or higher monohydroxy Carboxylic acids constitute branched components having at least two branch points.
  • the bifunctional hydroxycarboxylic acid used in the present embodiment is not particularly limited as long as it has one hydroxyl group and one carboxyl group in the molecule.
  • Those obtained by ring-opening lactones such as -hydroxy-3-methylbutyric acid, 2-methyllactic acid, 2-hydroxycaproic acid, 2-hydroxyisocaproic acid, or caprolactone, or difunctional hydroxy groups by ring opening during the reaction
  • lactones such as lactide which is a carboxylic acid, glycolide, mandelide, caprolactone, valerolactone and the like, or a mixture thereof.
  • any of D-form, L-form and racemate may be used.
  • it is lactic acid, more preferably L-lactic acid, glycolic acid or ⁇ -caprolactone.
  • L-lactic acid is easily available, and by using poly (L-lactic acid) as a main chain, it is possible to obtain a highly safe and highly biocompatible polymer.
  • diol and dicarboxylic acid are not particularly limited, and known compounds can be used.
  • ethylene glycol, propylene glycol, butylene glycol, and dicarboxylic acid can be used as the diol
  • succinic acid, glutaric acid, adipic acid and the like can be used as the dicarboxylic acid.
  • the trifunctional or higher functional carboxylic acid is not particularly limited as long as it has a total of three or more carboxyl groups in the molecule.
  • Compounds 1 and 2 can be synthesized, for example, by the methods described in the following documents.
  • a desired star-shaped branched polymer having a carboxyl group at the end can be obtained.
  • L-lactic acid, glycolic acid or ⁇ -caprolactone 1,2,3-benzene tricarboxylic acid, 1,2,4-benzene tricarboxylic acid, 1,3,5- Benzenetricarboxylic acid, 1,2,3-propanetricarboxylic acid, propene-1,2,3-tricarboxylic acid, 1,3,5-cyclohexanetricarboxylic acid, 1,3,5-pentanetricarboxylic acid, 2-methylpropanetricarboxylic acid Preferred is the combination with an acid or benzene-1,3,5-triacetic acid.
  • the combination with -tetracarboxylic acid is preferred.
  • the trifunctional or higher monohydroxycarboxylic acid is not particularly limited as long as it has one hydroxyl group and two or more carboxyl groups in the molecule.
  • Specific examples thereof include malic acid, 2- (hydroxymethyl) -2- (carboxymethoxymethyl) -1,3-propanediylbisoxydiacetic acid (compound 3), 2- (hydroxymethyl) -2- (carboxy) Any one selected from the group consisting of methoxyethyl) -1,3-propanediylbisoxydipropionic acid (compound 4) can be used.
  • malic acid and the compound 3 can be mentioned.
  • chemical equivalents such as acid anhydride derivatives of the above carboxylic acids can also be used.
  • a desired hyperbranched polymer having a carboxyl group at the end can be obtained.
  • a combination using monohydroxydicarboxylic acid L-lactic acid, glycolic acid or ⁇ -caprolactone and malic acid are preferable, and as a combination using monohydroxytricarboxylic acid, L-lactic acid, glycolic acid or Preference is given to ⁇ -caprolactone and compound 1.
  • the organic onium salt used as a catalyst in the present embodiment is composed of an organic onium cation and a sulfonate anion, and is represented by the following formula (1).
  • the organic onium cation is a cation generated by coordination bonding of a proton or another cation to a lone electron pair in a compound containing an element having a lone electron pair.
  • R 1 to R 4 each independently represent a hydrogen atom, or a linear or branched aliphatic hydrocarbon group which may have a substituent, an alicyclic hydrocarbon group, an aromatic hydrocarbon Represents a group or a heterocyclic group.
  • A represents a nitrogen atom or a phosphorus atom.
  • one to three of R 1 to R 4 may be a hydrogen atom.
  • X represents a sulfonic acid group.
  • an alkyl group As a linear or branched aliphatic hydrocarbon group, an alkyl group, an alkenyl group, an alkynyl group etc. can be mentioned.
  • a cycloalkyl group As an alicyclic hydrocarbon group, a cycloalkyl group can be mentioned.
  • an aromatic hydrocarbon group an aryl group and an aralkyl group can be mentioned.
  • the heterocyclic group include nitrogen-containing monocyclic or fused ring compounds.
  • a halogen atom can be mentioned as substituents, such as said aliphatic hydrocarbon group. Preferably it is a fluorine atom.
  • Trialkylammonium such as triethylammonium, triethylammonium, ethyldimethylammonium, diethylmethylammonium, tetramethylammonium, tetraethylammonium, tetra-n-propylammonium, tetraisopropylammonium, tetra-n-butylammonium, anilinium, diphenylammonium, tetra Aromatic ammonium such as phenylammonium, alicyclic ammonium such as N, N-dimethylpyrrolidinium, N, N-dimethylpiperidinium, N, N-dimethylmorpholinium, pyridinium, pyrazolium, N-methylimidazolium And nitrogen-containing heterocyclic compounds such as N-methylpyridinium.
  • Trialkylammonium such as triethylammonium, triethylammonium, eth
  • nitrogen-containing heterocyclic compounds may have a substituent such as an alkyl group, an aralkyl group, a halogen group or an alkoxy group bonded thereto.
  • a substituent such as an alkyl group, an aralkyl group, a halogen group or an alkoxy group bonded thereto.
  • anilinium pyrazolium and N-methylimidazolium.
  • anilinium is preferably a fluorine-substituted compound, specifically pentafluoroanilinium (or pentafluorophenyl ammonium).
  • chlorine substitution specifically dichloroanilinium at any substitution position, and trichloroanilinium at any substitution position are preferable.
  • Triaryl phosphonium aryl dialkyl phosphonium, diaryl alkyl phosphonium, trialkyl phosphonium etc. can be mentioned.
  • Preferred is triaryl phosphonium, specifically triphenyl phosphonium.
  • the organic onium salt used in this embodiment catalyzes a transesterification reaction as a Brnsted acid, so the smaller the pKa (the stronger the acidity), the better. Therefore, sulfonic acid is used as the anion.
  • the sulfonic acid may have a substituent, an alkylsulfonic acid such as methanesulfonic acid, ethanesulfonic acid, octanesulfonic acid, dodecanesulfonic acid, etc., and may have a substituent, benzenesulfonic acid, p And arylsulfonic acids such as toluenesulfonic acid, naphthalenesulfonic acid, decylbenzenesulfonic acid, dodecylbenzenesulfonic acid and the like.
  • a superstrong acid It is preferably a superstrong acid, and specific examples thereof include halogenated alkylsulfonic acids such as trifluoromethanesulfonic acid, perfluoroethanesulfonic acid, perfluorobutanesulfonic acid, perfluorohexanesulfonic acid and the like.
  • halogenated alkylsulfonic acids such as trifluoromethanesulfonic acid, perfluoroethanesulfonic acid, perfluorobutanesulfonic acid, perfluorohexanesulfonic acid and the like.
  • H 0 Hammett acidity function
  • trifluoromethanesulfonic acid is ⁇ 14.5
  • perfluoroethanesulfonic acid is ⁇ 14.0
  • perfluorobutanesulfonic acid is ⁇ 13.2
  • perfluorohexanesulfonic acid is ⁇ 12.3.
  • the organic onium salt used in the present embodiment is not particularly limited as long as it is a combination of the above-mentioned nitrogen cation or phosphorus cation and a sulfonate anion, preferably pentafluorophenylammonium and trifluoromethanesulfonic acid.
  • Fluorophenyl ammonium triflate hereinafter abbreviated as PFPAT
  • TPPT triphenylphosphonium triflate
  • the amount of the trifunctional or higher functional carboxylic acid used in the present embodiment is 0.1 to 10 moles, more preferably 0.1 to 5 moles with respect to 100 moles of the bifunctional hydroxycarboxylic acid. If the amount is less than 0.1 mol, sufficient effects can not be obtained because the amount of terminal carboxyl groups is small, and if the amount is more than 10 mol, the polymer chain to be a branch component becomes too short.
  • the concentration (catalyst / raw material) of the catalyst relative to the bifunctional hydroxycarboxylic acid and the trifunctional or higher carboxylic acid (hereinafter referred to as the raw material) is 0.01 to 2 mo1%, more preferably 0.1 to 1 mo1% . If the amount is less than 0.01 mol%, sufficient reactivity can not be obtained to obtain a high conversion rate, and if the amount is more than 2 mol%, a corresponding effect can not be obtained.
  • the amount of the trifunctional or higher monohydroxypolycarboxylic acid used in the present embodiment is 0.1 to 10 moles, more preferably 0.5 to 10 moles with respect to 100 moles of the bifunctional hydroxycarboxylic acid. If the amount is less than 0.1 mol, sufficient effects can not be obtained because the amount of terminal carboxyl groups is small. If the amount is more than 10 mol, the physical properties of the main chain component can not be exhibited.
  • the concentration (catalyst / raw material) of the catalyst with respect to the bifunctional hydroxycarboxylic acid and the trifunctional or higher monohydroxypolycarboxylic acid (hereinafter referred to as the raw material) is 0.01 to 2 mol%, more preferably 0.1 to 1 mol. %. If the amount is less than 0.01 mol%, sufficient reactivity can not be obtained to obtain a high conversion rate, and if the amount is more than 2 mol%, a corresponding effect can not be obtained.
  • the solvent is used to azeotropically remove the water produced by the dehydration condensation reaction.
  • a solvent benzene, toluene, xylene or the like can be used. From the viewpoint of operability, the amount used is about 1 to 3 times the volume ratio of the reactive hydroxycarboxylic acids.
  • the reaction temperature is preferably as high as possible, but since it needs to be azeotropically dehydrated, it becomes the azeotropic temperature of the solvent.
  • the reaction temperature is 80 to 220 ° C., more preferably 110 to 160 ° C.
  • the molecular weight of the produced polymer depends on the reaction temperature and reaction time, and can be appropriately selected according to the target molecular weight, polymerization temperature, type of catalyst, concentration of catalyst, and the like.
  • the preferred molecular weight of the present invention is 3,000 to 300,000, more preferably 5,000 to 150,000, in weight average molecular weight.
  • the organic onium salt catalyst used in the present embodiment can be reused. That is, after polymerization, the reaction mixture is diluted with methanol to precipitate a polymer, and after separation by filtration, the catalyst can be recovered by removing the solvent from the filtrate. The recovered catalyst can be used for the next reaction as it is after removing the solvent from the filtrate. If necessary, it can be purified and used by recrystallization.
  • the star-branched polymer obtained according to the present embodiment is obtained as a mixture with a linear polymer due to the nature of the reaction, it is produced by changing the reaction conditions such as the molar ratio of the core component and the reaction temperature. You can control the ratio.
  • the formation ratio can be determined by comparing and quantifying the number of moles of carboxylic acid ends of the polymer and the number of moles of hydroxyl groups.
  • the carboxyl group can be quantified by converting the polymer into a methyl ester by diazomethane treatment and quantifying the methyl group by NMR.
  • the hydroxyl group can be determined by quantifying a methylene group or methine group to which a hydroxyl group is bonded from NMR.
  • the hyperbranched polymer obtained by the present embodiment may be obtained as a mixture of a dendritic polymer and a comb polymer on the character of the reaction.
  • the two groups can not be distinguished spectroscopically, but in any case, the ratio of hydroxyl group to carboxyl group is constant at the terminal group of the polymer.
  • the ratio of both terminal groups can be determined by comparing and quantifying the number of moles of carboxylic acid ends and the number of moles of hydroxyl groups.
  • the carboxyl group can be quantified by converting the polymer into a methyl ester by diazomethane treatment and quantifying the methyl group by NMR.
  • the hydroxyl group can be determined by quantifying a methylene group or methine group to which a hydroxyl group is bonded from NMR.
  • a biodegradable branched polymer is directly synthesized from a difunctional hydroxycarboxylic acid and a trifunctional or higher carboxylic acid or a trifunctional or higher monohydroxycarboxylic acid by using an organic onium salt catalyst.
  • organic onium salt catalyst can do.
  • trifunctional or higher monohydroxycarboxylic acids usually have no solubility other than water.
  • the organic onium salt catalyst is stable to water, a commercially available aqueous solution of lactic acid can be used as it is, so that a uniform reaction site can be secured at the initial stage of the reaction. Therefore, the manufacturing process can be simplified, and the manufacturing efficiency can be improved.
  • the organic onium salt catalyst used in the present invention can be reused, cost reduction and waste reduction can be achieved.
  • the star-shaped and multi-branched biodegradable polymers obtained by the present embodiment have a carboxyl group at the end, they interact with other molecules, such as covalent bonding and salt formation. It is possible to form an ionic bond by As a result, it becomes easy to bind to a chemical substance such as a drug, and application to drug delivery can also be expected. Also, by controlling the length and molecular weight of the polymer chain, it is possible to impart high strength and elasticity to the melt. Furthermore, by setting it as a branched structure, the crystallinity of the polymer is reduced, and the effect of improving the biodegradability can also be obtained.
  • Second Embodiment In the method for producing a biodegradable polymer according to the present embodiment, direct dehydration polycondensation of component A consisting of bifunctional hydroxycarboxylic acid and component B consisting of polyhydroxypolycarboxylic acid in the presence of an organic onium salt catalyst It is characterized by doing.
  • the biodegradable polymer obtained according to the present embodiment is a network polymer having a bifunctional hydroxycarboxylic acid as a main chain component and a polyhydroxypolycarboxylic acid as a crosslinking component.
  • the bifunctional hydroxycarboxylic acid used in the present embodiment the same one as in Embodiment 1 can be used.
  • the bifunctional hydroxycarboxylic acid may be a compound containing an aromatic ring, such as p-hydroxybenzoic acid, m-hydroxybenzoic acid, 4-hydroxyphenylacetic acid and the like.
  • an optical isomer any of D-form, L-form and racemate may be used.
  • it is lactic acid or glycolic acid.
  • L-lactic acid is easily available, and by using poly (L-lactic acid) as a main chain, a network polymer having high rigidity and tensile strength and high transparency can be obtained.
  • the polyhydroxypolycarboxylic acid is not particularly limited as long as it has two or more hydroxyl groups and two or more carboxyl groups in the molecule.
  • Specific examples thereof include tartaric acid, 4,4'-bioxepane-7,7'-dione, 5,5 '-(1-methylethylidene) bis-2-oxepanone and the like.
  • it is tartaric acid, 4,4'-bioxepane-7,7'-dione. It is because tartaric acid is a natural product, is easy to obtain because it is inexpensive, and the degree of crosslinking can be set arbitrarily.
  • trifunctional or higher functional alcohols and trifunctional or higher functional carboxylic acids can also be used as chemical equivalents of polyhydroxypolycarboxylic acid.
  • the trifunctional or higher functional alcohol and the trifunctional or higher functional carboxylic acid are not particularly limited, and known compounds can be used.
  • glycerin, trimethylolpropane, trimethylolbutane, pentaerythritol, inositol and the like can be used as the trifunctional or higher functional alcohol.
  • trifunctional or higher functional carboxylic acids include aconitic acid, 1,2,3-benzenetricarboxylic acid, 1,3,5-benzenetricarboxylic acid, 1,2,4,5-benzenetetracarboxylic acid, 1,2 , 3,4-cyclopentane tetracarboxylic acid, 1,2,3,4-butane tetracarboxylic acid, ethylenediaminetetraacetic acid (EDTA) and the like can be used.
  • EDTA ethylenediaminetetraacetic acid
  • a network polymer having a desired branched chain can be obtained by combining the above-described bifunctional hydroxycarboxylic acid and the above-described polyhydroxypolycarboxylic acid.
  • lactic acid-tartaric acid glycolic acid-tartaric acid
  • lactic acid-4,4'-bioxepane-7,7'dione glycolic acid-4,4'-bioxepane-7,7 ' It is preferred to use a dione.
  • organic onium salt used as a catalyst in the present embodiment those similar to those described in Embodiment 1 can be used.
  • the organic onium salt catalyst used in the present embodiment can be reused. That is, after polymerization, the reaction mixture is diluted with methanol to precipitate a polymer, and after separation by filtration, the catalyst can be recovered by removing the solvent from the filtrate. The recovered catalyst can be used as it is for the next reaction after solvent removal from the filtrate. If necessary, it can be purified and used by recrystallization.
  • the amount of polyhydroxypolycarboxylic acid used in the present embodiment is 0.01 to 10 moles, more preferably 0.1 to 1 mole with respect to 100 moles of bifunctional hydroxycarboxylic acid. This is because at least sufficient strength and elasticity can not be obtained more than 0.01 mol, and if it is more than 10 mol, the degree of cross-linking becomes high and it becomes insoluble in a solvent and can not be purified.
  • the concentration of the catalyst for bifunctional hydroxycarboxylic acid and polyhydroxypolycarboxylic acid is 0.01 to 1 mol%, more preferably 0.1 to 0.5 mol%. If it is less than 0.1 mol%, it takes a long time to obtain high molecular weight, and if it is more than 1 mol%, high molecular weight can not be obtained.
  • the solvent is used to azeotropically remove the water produced by the dehydration condensation reaction.
  • a solvent benzene, toluene, xylene or the like can be used. From the viewpoint of operability, the amount used is about 1 to 3 times the volume ratio of the reactive hydroxycarboxylic acids.
  • the reaction temperature is preferably as high as possible, but since it needs to be azeotropically dehydrated, it becomes the azeotropic temperature of the solvent.
  • the reaction temperature is 80 to 200 ° C., more preferably 110 to 163 ° C.
  • the upper limit of the molecular weight of the produced polymer is recognized depending on the reaction temperature, and therefore, the polymerization may be carried out for the time when the upper molecular weight obtained at that temperature is obtained. Therefore, the polymerization time can be appropriately selected depending on the target molecular weight, polymerization temperature, type of catalyst, concentration of catalyst, and the like.
  • the preferred molecular weight of the present invention is 10,000 to 500,000, and more preferably 30,000 to 100,000 in weight average molecular weight.
  • the degree of crosslinking of the network polymer obtained by the present embodiment can be adjusted by the proportion of polyhydroxypolycarboxylic acid used.
  • the polyhydroxypolycarboxylic acid can be added in any proportion, but if the degree of crosslinking is too high the network polymer becomes insoluble in most solvents.
  • the degree of cross-linking in the present invention is the content of an ester as a branched component, and a substance soluble in a solvent can be calculated by NMR analysis.
  • the preparation ratio can be made the degree of crosslinking.
  • the degree of crosslinking of the network polymer obtained by the present embodiment can be changed by selecting the reaction temperature, particularly in the case of tartaric acid.
  • the degree of crosslinking increases as the reaction temperature increases.
  • the change of the degree of crosslinking due to the change of the reaction temperature can be controlled in the range of 48 hours after the start of the reaction, more preferably 16 hours after the start of the reaction.
  • the network polymer can be directly synthesized from the bifunctional hydroxycarboxylic acid and the polyhydroxypolycarboxylic acid, and the activity is higher than that of the conventional catalyst. Have. Thereby, the manufacturing process can be simplified and the manufacturing efficiency can be improved.
  • the organic onium salt catalyst can be reused, cost reduction and waste reduction can be achieved.
  • the catalyst is stable to water, a commercially available aqueous solution of lactic acid or glycolic acid can be used as it is. This is advantageous in the sense that a uniform reaction site can be secured at the initial stage of the reaction since polyhydroxypolycarboxylic acid usually has no solubility other than water.
  • the polyester obtained according to the present embodiment is a biodegradable network polymer having a bifunctional hydroxycarboxylic acid as a main chain component and a polyhydroxypolycarboxylic acid as a crosslinking component, and by controlling the degree of crosslinking and the molecular weight. It is possible to impart high strength and elasticity to the melt. This can impart the desired rheological properties required for melt molding. Moreover, the crystallinity of the polymer is reduced by crosslinking, and the effect of improving the biodegradability can also be obtained.
  • Synthesis Example 1 (PFPAT Synthesis) Dissolve 5.0 g of 2,3,4,5,6-pentafluoroaniline (manufactured by Tokyo Chemical Industry Co., Ltd.) in 25 ml of dichloromethane and slowly add 2.4 ml of trifluoromethanesulfonic acid (manufactured by Tokyo Chemical Co., Ltd.) while cooling with ice. Mixed and stirred. The precipitated crystals were suction filtered, the filtrate was washed with diethyl ether and dried under reduced pressure. A slightly purplish milky crystal was obtained. The yield was 79.6%. The melting point was 211.5 ° C.
  • the solvent was distilled off from the obtained polymer solution.
  • the residue was dissolved in 20 ml of dichloromethane (CH 2 Cl 2 ) and the solution obtained was then poured into 150 ml of ice-cold methanol (CH 3 OH) to precipitate the polymer.
  • the precipitate was suction filtered and dried under reduced pressure.
  • Table 1 shows the results.
  • Example No. 1, 2, 3 When refluxing with toluene as solvent for 24 hours, 48 hours, and 72 hours (Experiment No. 1, 2, 3), using ethylbenzene as solvent as reflux for 24 hours, 48 hours (Experiment No. 4, 5), And after refluxing in toluene for 16 hours, after distilling toluene off, the example (experiment number 6, 7) refluxed at 130 degreeC for 48 hours and 72 hours in the state of a non-solvent is shown.
  • the ester ratio in the table is defined as follows according to the degree of esterification of the two hydroxyl groups whose reactivity was lower than that of the carboxyl group with respect to L-tartaric acid.
  • “None” refers to a state in which only two carboxyl groups of L-tartaric acid are esterified and two hydroxyl groups are free. Further, “mono” refers to a state in which two carboxyl groups and one hydroxyl group of L-tartaric acid are esterified and one hydroxyl group is free. In addition, “bis” refers to a state in which two carboxyl groups and two hydroxyl groups of L-tartaric acid are esterified. The ester ratio was determined from the measurement results of 1 H-NMR and HH-cosy NMR.
  • Example 2 The purpose of this experiment is to find conditions that are soluble in thermal solvents such as toluene and ethylbenzene, and that they are all soluble in dichloromethane and chloroform after synthesis so that purification is possible even if the weight average molecular weight exceeds 10,000. is there.
  • the reaction was performed under the same conditions as in Example 1 except that toluene was used as the solvent, the reaction time was 24 hours, and the feed molar ratio of L-lactic acid and L-tartaric acid was changed.
  • the results are shown in Table 2.
  • LLA represents L-lactic acid
  • LTA represents L-tartaric acid.
  • Example 3 The influence of the type of polyhydroxypolycarboxylic acid was investigated. L-lactic acid alone (LLA: Experiment No. 1), L-tartaric acid (LTA) was replaced with 4,4′-bioxepan-7,7′-dione (LLA-BL: Experiment No. 14), The procedure was carried out under the same conditions as in Example 1 except that the feed molar ratio of (LLA / LTA, LLA / BL) was changed to (1 mol%, and the solvent was 10 ml relative to 10 ml of L-lactic acid). The results are shown in Table 3. Here, the ester ratios in the table are as described in Example 1 for tartaric acid.
  • LLA-LTA L-lactic acid-L-tartaric acid
  • LLA-BL L-lactic acid-4,4'-bioxepane-7,7'-dione
  • LLA L-lactic acid
  • the network polymer could be synthesized as in the case of using L-tartaric acid.
  • Example 4 The reaction was carried out under the same conditions as in Example 3 except that PFPAT was used instead of TPPT as the catalyst, toluene was used as the solvent, and the L-tartaric acid charge was changed.
  • the concentration of PFPAT is (catalyst / (L-lactic acid + L-tartaric acid) ratio: 0.1 mol%).
  • Table 4 shows the results.
  • Experiment No. 14 is one refluxed for 12 hours in toluene, and Experiment No. 14 has a content (analytical value) of L-tartaric acid of 1 mol%.
  • Experiment Nos. 15 and 16 are those that are refluxed for 24 hours in toluene, and Experiment No. 15 has a content (analytical value) of L-tartaric acid of 0.1 mol%.
  • Experiment No. 17 has a content (analytical value) of bislactone of 0.1 mol%.
  • LLA-LTA L-lactic acid-L-tartaric acid
  • LLA-BL L-lactic acid-4,4'-bioxepane-7,7'-dione
  • LLA L-lactic acid
  • Example 5 4 g of 90% aqueous solution of L-lactic acid, 8 ml of toluene, 10 ml of water, 0.1017 g of pyromellitic acid (ratio of pyromellitic acid / L-lactic acid: 0.1 mol%), 0.0164 g of TPPT as a catalyst (catalyst / L-lactic acid ratio: 0. 1 mol%) were mixed in a flask to dissolve all pyromellitic acid at room temperature. An azeotropic dehydration operation was performed for 96 hours while distilling off water outside the system under normal pressure with a Dean Stark trap attached.
  • the solvent was distilled off from the obtained polymer solution.
  • the residue was dissolved in 20 ml of dichloromethane (CH 2 Cl 2 ) and the solution obtained was then poured into 200 ml of ice-cold methanol (CH 3 OH) to precipitate the polymer.
  • the precipitate was suction filtered and dried under reduced pressure.
  • the solvent is distilled off from the solution obtained, and the polymer is dried under reduced pressure.
  • Example 6 4 g of 90% aqueous solution of L-lactic acid, 8 ml of 2-methyl-2-pentanol, 0.1017 g of pyromellitic acid (ratio of pyromellitic acid / L-lactic acid: 1 mol%), 0.0164 g of TPPT as catalyst (catalyst / L-lactic acid ratio: 0.1 mol%) were mixed in the flask. An azeotropic dehydration operation was performed for 18 hours while distilling off water outside the system under normal pressure by attaching a Dean Stark trap.
  • Example 7 4 g of 90% aqueous solution of L-lactic acid, 8 ml of xylene, 0.0985 g of 1,2,3,4-cyclopentane tetracarboxylic acid (1,2,3,4-cyclopentane tetracarboxylic acid / L-lactic acid ratio: 1 mol%)
  • a catalyst 0.0164 g of TPPT (catalyst / L-lactic acid ratio: 0.1 mol%) was mixed in a flask.
  • An azeotropic dehydration operation was carried out for 48 hours while distilling off water outside the system under normal pressure with a Dean Stark trap attached. Thereafter, in the same manner as in Example 1, the polymer was separated from the obtained polymer solution and dried under reduced pressure.
  • Example 8 4% aqueous solution of 90% L-lactic acid, 8 ml of toluene, 0.27 g of L-malic acid (L-malic acid / L-lactic acid ratio: 5 mol%), 0.014 g of PFPAT as a catalyst (catalyst / (L-lactic acid + L malic acid ratio) ): 0.1 mol%) were mixed in the flask.
  • An azeotropic dehydration operation was performed for 24 hours while distilling off water outside the system under normal pressure with a Dean Stark trap attached. Thereafter, in the same manner as in Example 1, the polymer was separated from the obtained polymer solution and dried under reduced pressure.
  • Example 9 4% aqueous solution of 90% L-lactic acid, 8 ml of toluene, 0.054 g of L-malic acid (L-malic acid / L-lactic acid ratio: 5 mol%), 0.014 g of PFPAT as a catalyst (catalyst / (L-lactic acid + L malic acid ratio) ): 0.1 mol%) were mixed in the flask. Azeotropic dehydration was carried out for 12 hours while distilling off water outside the system under normal pressure with a Dean Stark trap attached. Thereafter, in the same manner as in Example 1, the polymer was separated from the obtained polymer solution and dried under reduced pressure.
  • Table 5 shows the feed value and analysis value of the molar ratio of tetracarboxylic acid / lactic acid, and the result of molecular weight measurement by GPC.
  • the tetracarboxylic acid is pyromellitic acid in Examples 5 and 6, and 1,2,3,4-cyclopentane tetracarboxylic acid in Example 7.
  • Table 6 shows the feed value and analysis value of the molar ratio of L-malic acid / lactic acid, and the result of molecular weight measurement by GPC. It also shows the concentration of unreacted hydroxyl group of L-malic acid.
  • the solvent was distilled off from the obtained polymer solution.
  • the residue was dissolved in 0.5 ml of chloroform (CHCl 3 ), and the obtained solution was poured into 10 ml of ice-cold diethyl ether (CH 3 CH 2 OCH 2 CH 3 ) to precipitate a polymer.
  • the precipitate was suction filtered and dried under reduced pressure.
  • the solvent was distilled off from the obtained polymer solution.
  • the residue was dissolved in 0.5 ml of chloroform, and the resulting solution was poured into 10 ml of ice-cold diethyl ether to precipitate a polymer.
  • the precipitate was suction filtered and dried under reduced pressure.

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)

Abstract

L'invention porte sur un polymère biodégradable comprenant un poly(acide hydroxycarboxylique) ayant une structure ramifiée ou réticulée qui peut être obtenu par utilisation d'un sel d'onium organique comme catalyseur pour la polycondensation par déshydratation. Le catalyseur sel d'onium organique a une activité supérieure à celle de catalyseurs classiques et par conséquent permet la simplification du procédé de production pour le polymère biodégradable et l'amélioration du rendement de production du polymère biodégradable. Le catalyseur sel d'onium organique peut être réutilisé et par conséquent permet également la réduction du coût ou de matières de déchet. Le polymère biodégradable peut conférer une résistance élevée et une élasticité élevée à un produit fondu de celui-ci et peut également conférer des propriétés rhéologiques requises pour le moulage à l'état fondu au produit fondu de celui-ci, en raison du fait que le polymère biodégradable a une structure ramifiée ou réticulée.
PCT/JP2008/073584 2008-01-09 2008-12-25 Procédé de fabrication de polymère biodégradable WO2009087910A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2009548886A JPWO2009087910A1 (ja) 2008-01-09 2008-12-25 生分解性ポリマーの製造方法

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP2008002275 2008-01-09
JP2008-002275 2008-01-09
JP2008-038683 2008-02-20
JP2008038683 2008-02-20

Publications (1)

Publication Number Publication Date
WO2009087910A1 true WO2009087910A1 (fr) 2009-07-16

Family

ID=40853034

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2008/073584 WO2009087910A1 (fr) 2008-01-09 2008-12-25 Procédé de fabrication de polymère biodégradable

Country Status (2)

Country Link
JP (1) JPWO2009087910A1 (fr)
WO (1) WO2009087910A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012140383A (ja) * 2011-01-05 2012-07-26 Kyoto Institute Of Technology ラクチドの製造方法
WO2021241607A1 (fr) * 2020-05-29 2021-12-02 ポリプラスチックス株式会社 Procédé de production de résine cristalline liquide
CN113912826A (zh) * 2021-08-13 2022-01-11 温州医科大学 一种含羟基聚酯的制备方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6392641A (ja) * 1986-10-08 1988-04-23 Wako Pure Chem Ind Ltd 新規共重合体
JPH07501102A (ja) * 1991-11-21 1995-02-02 サザン・リサーチ・インスティテュート オキシカルボン酸及びポリカルボン酸から得られるポリマー
JPH10287735A (ja) * 1997-04-10 1998-10-27 Kanebo Ltd ポリ乳酸組成物およびその製造方法ならびに該組成物の成形品
JPH11240941A (ja) * 1998-02-26 1999-09-07 Nishikawa Rubber Co Ltd 加水分解性及び生分解性のポリヒドロキシカルボン酸共重合樹脂の製造方法
JP2001516374A (ja) * 1997-01-15 2001-09-25 ミシガン・モレキュラー・インスティチュート 芳香族ポリエステルを製造するための溶融重合法
WO2008149661A1 (fr) * 2007-05-31 2008-12-11 National University Corporation Kyoto Institute Of Technology Procédé de production d'un ester d'acide gras

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6392641A (ja) * 1986-10-08 1988-04-23 Wako Pure Chem Ind Ltd 新規共重合体
JPH07501102A (ja) * 1991-11-21 1995-02-02 サザン・リサーチ・インスティテュート オキシカルボン酸及びポリカルボン酸から得られるポリマー
JP2001516374A (ja) * 1997-01-15 2001-09-25 ミシガン・モレキュラー・インスティチュート 芳香族ポリエステルを製造するための溶融重合法
JPH10287735A (ja) * 1997-04-10 1998-10-27 Kanebo Ltd ポリ乳酸組成物およびその製造方法ならびに該組成物の成形品
JPH11240941A (ja) * 1998-02-26 1999-09-07 Nishikawa Rubber Co Ltd 加水分解性及び生分解性のポリヒドロキシカルボン酸共重合樹脂の製造方法
WO2008149661A1 (fr) * 2007-05-31 2008-12-11 National University Corporation Kyoto Institute Of Technology Procédé de production d'un ester d'acide gras

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012140383A (ja) * 2011-01-05 2012-07-26 Kyoto Institute Of Technology ラクチドの製造方法
WO2021241607A1 (fr) * 2020-05-29 2021-12-02 ポリプラスチックス株式会社 Procédé de production de résine cristalline liquide
JP7072733B1 (ja) * 2020-05-29 2022-05-20 ポリプラスチックス株式会社 液晶性樹脂の製造方法
CN113912826A (zh) * 2021-08-13 2022-01-11 温州医科大学 一种含羟基聚酯的制备方法

Also Published As

Publication number Publication date
JPWO2009087910A1 (ja) 2011-05-26

Similar Documents

Publication Publication Date Title
JP6826533B2 (ja) イソシアネートを使用しない炭酸エステル修飾ポリマーの合成
CN104797627B (zh) 具有高分子量的脂肪族聚碳酸酯共聚物及其制备方法
TW201231497A (en) Polyester resin composition and preparing method thereof
JP2015518915A (ja) ポリエステル樹脂およびその製造方法
Feng et al. A designed synthetic strategy toward poly (isosorbide terephthalate) copolymers: a combination of temporary modification, transesterification, cyclization and polycondensation
Li et al. Aromatic-aliphatic random and block copolyesters: synthesis, sequence distribution and thermal properties
KR101532435B1 (ko) 락트산 공중합체 및 그 제조방법
CN111072941A (zh) 一种双环氧化合物合成线型、多官能度聚酯多元醇的方法
EP3411423A1 (fr) Transestérification de poly(acide lactique) à l'aide des huiles naturelles
KR101693546B1 (ko) 가공성과 유연성이 우수한 폴리유산계 생분해성 수지 조성물 및 그로부터 제조되어진 생분해성 필름
JP2009510212A (ja) ポリ乳酸の調製のための新規方法
WO2009087910A1 (fr) Procédé de fabrication de polymère biodégradable
Lee et al. Ring-opening polymerization of a macrocyclic lactone monomer isolated from oligomeric byproducts of poly (butylene succinate)(PBS): An efficient route to high-molecular-weight PBS and block copolymers of PBS
WO2022143914A1 (fr) Ester d'acide gras polyhydroxy et son procédé de préparation
Yuan et al. Synthesis and characterization of star polylactide by ring-opening polymerization of L-lactic acid O-carboxyanhydride
JP5990179B2 (ja) スターポリマーの製造方法
JP2010090385A (ja) ベチュリンから得られるポリマー及びその製造法
US8853330B2 (en) Hybrid polymers
George et al. Carbodiimide-mediated synthesis of poly (L-lactide)-based networks
JP4491626B2 (ja) ベチュリンから得られるポリマー及びその製造法
Omar et al. Star-shaped Poly (hydroxybutyrate) s from bio-based polyol cores via zinc catalyzed ring-opening polymerization of β-Butyrolactone
JP3374616B2 (ja) 脂肪族ポリエステル共重合体の製造法
JP2008056894A (ja) 高分岐ポリマー及びその製造方法、並びに、高分岐ポリマー合成用モノマー及びその前駆体
Zhao et al. Biodegradable poly (butylene succinate-co-butylene dimerized fatty acid) s: Synthesis, crystallization, mechanical properties, and rheology
CN102676603B (zh) 一种制备聚己内酯的方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08869541

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2009548886

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08869541

Country of ref document: EP

Kind code of ref document: A1