JP2021193159A - Polyester copolymer - Google Patents

Abstract

To provide a polyester copolymer exerting excellent restorability to repeated drawing.SOLUTION: The polyester copolymer is composed of ester bond-formable monomer residues as main constitutional units, and includes no hydrophilic segment in a molecular chain, wherein when two kinds of the ester bond-formable monomers are monomer A, and monomer B respectively, the rate of change of a crystal amount derived from the monomer A represented by the following formula is 0.30-10.00. A rate of change of a crystal amount=a crystal amount when drawing just before breaking/a crystal amount before drawing.SELECTED DRAWING: None

Description

The present invention relates to polyester copolymers, in particular polyester copolymers capable of exhibiting biodegradability or bioabsorbability.

Polyesters produced from ester bond-forming monomers represented by polylactic acid, polyglycolic acid, polycaprolactone or copolymers thereof have attracted attention as biodegradable or bioabsorbable polymers, for example, sutures and the like. It is used in various fields such as medical materials, pharmaceuticals, pesticides, and sustained-release materials such as fertilizers. Further, it is expected as a biodegradable general-purpose plastic as a packaging material for containers and films. Many biodegradable or bioabsorbable polymers with improved flexibility have been reported for suitable use in such applications.

For example, as a method for improving flexibility, Patent Document 1 describes a method for improving flexibility by controlling the component ratio of caprolactone and glycolide or lactide, and Patent Document 2 describes a method for controlling the randomness of a monomer sequence. Discloses how to improve flexibility in.

Further, Patent Document 3 describes a method for improving biodegradability without affecting excellent mechanical strength by modifying the molecular terminal, and Patent Document 4 describes a hydrophilic segment content, molecular motility, and crystallinity. A method for synthesizing a polyester copolymer having excellent biodegradability and biofollowability by controlling sex is disclosed.

Japanese Unexamined Patent Publication No. 3-269013 International Publication No. 2019/035357 Japanese Unexamined Patent Publication No. 2000-143781 International Publication No. 2019/187569

Some medical devices are buried in the body or attached to the skin, and in that case, it is required to maintain the original shape against repeated movements of the living body. However, although the methods described in Patent Documents 1 to 4 are recognized for improving flexibility and biodegradability, they do not mention resilience to repeated stretching, and further improvements are made for use in medical applications. It was necessary.

Therefore, it is an object of the present invention to provide a polyester copolymer which exhibits excellent resilience to repeated stretching.

The present invention for solving the above problems is as follows.

A polyester copolymer containing two types of ester bond-forming monomer residues as main constituent units and containing no hydrophilic segment in the molecular chain.
When the two types of ester bond-forming monomers are Monomer A and Monomer B, respectively, the crystal amount change rate represented by the following formula derived from Monomer A is 0.30 to 10.00, and the crystal amount of the polyester copolymer is Rate of change = Amount of crystals when stretched to just before breaking / Amount of crystals before stretching

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to obtain a polyester copolymer having a low Young's modulus, high tensile strength, biodegradability or bioabsorbability, excellent resilience, and suitable for medical use and elastomer use.

The polyester copolymer of the present invention is a copolymer having two types of ester bond-forming monomer residues as main constituent units. In the present specification, the two types of ester bond-forming monomers may be referred to as "monomer A" and "monomer B", respectively.

The "ester bond-forming monomer" refers to a polymer in which the monomer units are linked by an ester bond after polymerization, that is, a monomer that produces a polyester.

As the ester bond-forming monomer, it is preferable to use a hydroxycarboxylic acid. Further, lactone, which is a cyclic compound in which the hydroxy group and the carboxyl group of the hydroxycarboxylic acid are dehydrated and condensed in the molecule, and lactide, which is a cyclic compound in which the hydroxy group and the carboxyl group of the two hydroxycarboxylic acids are dehydrated and condensed, are also preferably used. be able to.

As the hydroxycarboxylic acid, it is particularly preferable to use an aliphatic hydroxycarboxylic acid. Examples of the aliphatic hydroxycarboxylic acid include lactic acid, glycolic acid, hydroxybutyric acid, hydroxyvaleric acid, hydroxypentanoic acid, hydroxycaproic acid, hydroxyheptanoic acid and the like, and in particular, lactic acid, glycolic acid, hydroxypentanoic acid and hydroxycaproic acid. Is preferable.

As lactic acid, L-lactic acid, D-lactic acid, and a mixture thereof can be used, but it is preferable to use L-lactic acid from the viewpoint of physical properties and biocompatibility of the obtained polymer. When a mixture is used as the monomer, the L-form content is preferably 85% or more, and more preferably 95% or more.

Examples of the lactone include caprolactone, dioxepanone, ethylene oxalate, dioxanone, 1,4-dioxane-2,3-dione, trimethylene carbonate, β-propiolactone, δ-valerolactone, β-propiolactone, β-. Butyrolactone, γ-butyrolactone, pivalolactone and the like can be used, and caprolactone and δ-valerolactone are particularly preferable.

As the lactide, dilactide in which two molecules of lactic acid are dehydrated and condensed, glycolide in which two molecules of glycolic acid are dehydrated and condensed, and tetramethylglycolide can be used.

As the ester bond-forming monomer, a derivative of the monomer exemplified above can also be used.

Among these, in the present invention, the monomer A and the monomer B are lactic acid, glycolic acid, hydroxybutyric acid, hydroxyvaleric acid, hydroxypentanoic acid, hydroxycaproic acid, hydroxyheptanic acid, caprolactone, dioxepanone, ethyleneoxalate, dioxanone, and the like. 1,4-Dioxane-2,3-dione, trimethylene carbonate, β-propiolactone, δ-valerolactone, β-propiolactone, β-butyrolactone, γ-butyrolactone, pivalolactone, dilactide, glycolide, and tetramethyl It is more preferable that the compound is selected from the group consisting of glycolide. The monomer A is particularly preferably lactic acid or glycolic acid, and the monomer B is particularly preferably caprolactone or δ-valerolactone.

In the present specification, of the two types of ester-binding monomers, the homopolymer composed only of the monomer residues thereof is referred to as monomer A, and the homopolymer having low crystallinity is referred to as monomer B. The crystallinity of the homopolymer can be measured using a differential scanning calorimetry (DSC) as follows.

The homopolymer is collected on an aluminum PAN and measured by the DSC method with a differential scanning calorimeter (EXTAR 6000; manufactured by Seiko Instruments Inc.) under the following condition A, and the heat of fusion is calculated. The higher the heat of fusion per unit weight, the higher the crystallinity. For example, the heat of fusion per unit weight of polylactic acid is 93 J / g when determined by the above method.
(Condition A)
Device name: EXSTAR 6000 (manufactured by Seiko Instruments Inc.)
Temperature conditions: 25 ° C → 250 ° C (10 ° C / min)
Standard substance: α-alumina

In the present invention, it is preferable that the crystallization rates of the monomer A residue and the monomer B residue are both less than 14%. When the crystallization rate is less than 14%, an increase in Young's modulus is suppressed, and a polyester copolymer suitable for medical materials and elastomer applications can be obtained. The crystallization rate of the monomer A residue and the monomer B residue is preferably 10% or less, and more preferably 5% or less.

The crystallization rate of the monomer residue referred to here is the product of the heat of melting per unit weight of the homopolymer consisting of only a certain monomer residue and the weight fraction of the monomer residue in the polyester copolymer of the present invention. The ratio of heat of fusion per unit weight of the monomer residue in the polyester copolymer of the present invention. That is, the crystallization rate of the monomer A residue is the product of the heat of melting per unit weight of the homopolymer composed of only the monomer A and the weight fraction of the monomer A residue in the polyester copolymer of the present invention in the polyester copolymer. It is the ratio of the heat of fusion per unit weight of the monomer A residue of the above. The crystallization rate of the monomer A residue and the monomer B residue indicates the ratio of forming a crystal structure in the monomer A residue or the monomer B residue of the polyester copolymer of the present invention, respectively.

In particular, when the monomer A residue is a lactic acid residue and the monomer B residue is a caprolactone residue, the crystallization rate of the lactic acid residue and the caprolactone residue is preferably less than 14%, preferably 10% or less. It is more preferable to have. The crystallization rate shall be specifically determined by the following method.

The polyester copolymer is dissolved in chloroform to a concentration of 5% by weight, the solution is transferred onto a "Teflon®" petri dish, and dried at normal pressure and room temperature for 24 hours. This was dried under reduced pressure to obtain a polyester copolymer film. The obtained polyester copolymer film is sampled in an alumina PAN, measured under the following conditions by the DSC method with a differential scanning calorimeter, and the heat of fusion is calculated from the measurement results of the temperature conditions (D) to (E). The crystallization rate is calculated from the following formula.

Crystallization rate of lactic acid residues = (heat of fusion per unit weight of lactic acid residues of polyester copolymer) / {(heat of fusion per unit weight of homopolymer consisting only of lactic acid residues) × (lactic acid residues in polyester copolymer) Weight fraction)} x 100 (%)
Crystallization rate of caprolactone residues = (heat of fusion per unit weight of caprolactone residues of polyester copolymer) / {(heat of fusion per unit weight of homopolymer consisting only of caprolactone residues) x (caprolactone residues in polyester copolymer) Weight fraction)} x 100 (%)
Device name: EXSTAR 6000 (manufactured by Seiko Instruments Inc.)
Temperature conditions: (A) 25 ° C → (B) 250 ° C (10 ° C / min) → (C) 250 ° C (5 min) → (D) -70 ° C (10 ° C / min) → (E) 250 ° C (10) ° C / min) → (F) 250 ° C (5 min) → (G) 25 ° C (100 ° C / min)
Standard substance: Alumina

In the present specification, the "monomer residue" is, in principle, a repeating unit of a chemical structure derived from the monomer in the chemical structure of a copolymer obtained by polymerizing two or more kinds of monomers containing the monomer. To tell. For example, lactic acid (CH ₃ CH (OH) COOH) and caprolactone (ε-caprolactone: the following formula)

When polymerized with and to form a copolymer of lactic acid and caprolactone,

Is a lactic acid monomer residue, and the unit represented by the following formula is a caprolactone monomer residue.

As an exception, when a dimer such as lactide is used as the monomer, the "monomer residue" means one of the twice-repeated structures derived from the dimer. For example, dilactide (L- (-)-lactide: formula below)

When caprolactone is polymerized, the chemical structure of the copolymer forms a structure in which the structure represented by the above formula (R1) is repeated twice as a dilactide residue. In this case, one lactic acid unit is formed. Is regarded as a "monomer residue", and it is considered that two "monomer residues", that is, two lactic acid residues are formed from dilactide.

The two types of monomer residues are defined as the "main constituent unit", which means that the sum of the numbers of the two types of monomer residues is the total number of monomer residues contained in the entire polymer including other monomer residues. When the sum is 100%, it is 50 mol% or more, and when the sum of all the monomer residues contained in the entire polymer is 100%, each residue is 20 mol% or more. means. For example, the main constituent unit is the monomer A residue and the monomer B residue, which means that the sum of the number of residues of the monomer A residue and the monomer B residue is the total number of monomer residues contained in the entire polymer. When the sum of 100% is taken as 100%, it means that the content is 50 mol% or more, the monomer A residue is 20 mol% or more, and the monomer B residue is 20 mol% or more. Here, the mole fraction of the monomer A residue, the monomer B residue, and other residues can be determined from the area value of the signal derived from each residue by nuclear magnetic resonance (NMR) measurement. For example, when the monomer A residue is a lactic acid residue and the monomer B residue is a caprolactone residue, the measurement can be performed by the method described in Measurement Example 1 described later.

From the above definition, the sum of the monomer A residue and the monomer B residue is 50 mol% or more when the sum of the total number of monomer residues contained in the entire polymer including other monomer residues is 100%. It is preferably 75 mol% or more, and more preferably 90 mol% or more. Further, the monomer A residue and the monomer B residue are each 20 mol% or more, preferably 30 mol% or more, and more preferably 40 mol% or more, respectively, from the above definition. A polymer in which the sum of the monomer A residue and the monomer B residue is 100% of the whole polymer, that is, the polymer consisting only of the monomer A and the monomer B is mentioned as a particularly preferable embodiment.

In addition, as long as the effect of the present invention is not impaired, another monomer that can be copolymerized with the two types of ester bond-forming monomers constituting the main constituent unit can be further copolymerized. As such a monomer, further one of the above-mentioned ester bond-forming monomers can be used.

It is also a preferred embodiment to copolymerize a monomer that functions as a linker. Examples of the monomer that functions as a linker include hydroxycarboxylic acids other than the two types of ester bond-forming monomers constituting the main constituent unit, dialcohols, dicarboxylic acids, amino acids, diamines, diisocyanates, and diepoxides.

In addition, in this specification, by including a monomer other than an ester bond-forming monomer in a constituent unit, the copolymer including a copolymer containing a constituent unit partially linked by a bond other than an ester bond is also referred to as "polyester copolymer". It shall be.

The polyester copolymer of the present invention is preferably biodegradable or bioabsorbable. Those skilled in the art will synthesize copolymers that exhibit appropriate biodegradability or bioabsorbability according to the application by appropriately combining the above-exemplified monomers and adjusting the amount ratio of the monomers within the range specified in the present invention. Will be able to.

The polyester copolymer of the present invention does not contain hydrophilic segments in the molecular chain. Here, the segment refers to a portion in which two or more of one type of monomer residues are continuously linked. Further, the hydrophilic segment means that the homopolymer composed of the monomer residues constituting the segment is water-soluble. The monomer residue forming the hydrophilic segment is called a hydrophilic monomer residue. Therefore, in the polyester copolymer of the present invention, the hydrophilic segment is not contained in the molecular chain, but the hydrophilic monomer residue can be contained in the molecular chain. That is, the polyester copolymer of the present invention containing hydrophilic monomer residues means an embodiment in which hydrophilic monomer residues are present in the molecular chain, but they are not arranged side by side in the molecular chain.

The mass ratio of the hydrophilic monomer residue to the total mass of 100% of the polyester copolymer is preferably 5% or less, more preferably 3% or less, further preferably 1% or less, and most preferably 0%.

The polyester copolymer of the present invention has a crystal content change rate of 0.30 to 10.00 derived from the monomer A represented by the following formula.

Rate of change in crystal amount = Crystal amount when stretched to just before fracture / Crystal amount before stretching Here, stretching until just before fracture refers to stretching to elongation obtained by multiplying fracture elongation by a safety factor of 0.8. The elongation at break can be determined by the method described in Measurement Example 4 using a tensile tester.

The amount of crystals can be determined by WAXS measurement of the polyester copolymer film. For example, in the case of a polyester copolymer in which the monomer A is lactic acid and the monomer B is caprolactone, the crystal amount can be determined by the method described in Measurement Example 3. The rate of change in the amount of change in the amount of crystals derived from the monomer A of the polyester copolymer is preferably 0.30 to 10.00, more preferably 0.50 to 8.00, and 1.00 to 5 in order to control the stability within a suitable range. .00 is even more preferred.

In the polyester copolymer of the present invention, the molar ratio of the monomer A residue to the monomer B residue approaches the homopolymer-like property when one of the monomers is excessively present. Therefore, the monomer A residue and the monomer B residue The molar ratio of the monomer A residue to 100% of the total number of moles is preferably 20 to 80%, more preferably 30 to 70%, still more preferably 40 to 60%.

In the polyester copolymer of the present invention, when the above-mentioned two types of ester bond-forming monomers are "monomer A" and "monomer B", respectively, the R value represented by the following formula is 0.45 or more and 0.99 or less. be.

R = [AB] / (2 [A] [B]) x 100
[A]: Mole fraction (%) of the monomer A residue in the polyester copolymer.
[B]: Mole fraction (%) of the monomer B residue in the polyester copolymer.
[AB]: Mole fraction (%) of the structure (AB, and BA) in which the monomer A residue and the monomer B residue are adjacent to each other in the polyester copolymer.
The R value is used as an index showing the randomness of the sequence of the monomer residues in the copolymer having two kinds of ester bond-forming monomer residues, that is, the monomer A residue and the monomer B residue as the main constituent units. For example, a random copolymer with a completely random monomer sequence has an R value of 1. Further, in the block copolymer, the R value is 0 to 0.44.

The R value can be determined by quantifying the ratio of the combination of two adjacent monomers (AA, BB, AB, BA) by nuclear magnetic resonance (NMR) measurement, specifically. It shall be measured by the method described in Measurement Example 1 described later.

When the R value is less than 0.45, the crystallinity is high, the molded product of the copolymer becomes hard, and the Young's modulus may increase. On the other hand, when the R value exceeds 0.99, the copolymer molded product becomes too soft and exhibits adhesiveness, which may reduce the handleability. From the same viewpoint, in the present invention, the R value of the polyester copolymer is preferably 0.45 to 0.85 or 0.50 to 0.99, more preferably 0.45 to 0.80 or 0.50 to 0.85. It is preferable, and more preferably 0.50 to 0.80.

The weight average molecular weight of the polyester copolymer of the present invention is preferably 100,000 to 1,000,000, more preferably 120,000 to 750,000, and 150,000 to 500, in order to control the crystal change rate in a suitable range. 000 is more preferred. The weight average molecular weight of the polyester copolymer can be measured, for example, by the method described in Measurement Example 2.

As an example, the polyester copolymer of the present invention contains two types of ester bond-forming monomers, Monomer A and Monomer B, in which the sum of the Monomer A residue and the Monomer B residue is 50 mol% of the total residue at the completion of polymerization. In addition, the macromer synthesis step of blending and polymerizing the monomer A residue and the monomer B residue so that each of them is 20 mol% or more of the total residue;
A mulching step of linking the macromers obtained in the macromer synthesis step or adding the monomer A and the monomer B to the macromer solution obtained in the macromer synthesis step;
It can be produced by a method for producing a polyester copolymer having the above.

[Macromer synthesis process]
In the macromer synthesis step, when the polymerization of monomer A and monomer B is theoretically completed, the sum of the monomer A residue and the monomer B residue is 50 mol% or more of the total residue, and the monomer A residue and the monomer B residue are present. Polymerization is carried out by blending each so as to be 20 mol% or more of all residues. As a result, a polyester copolymer having a monomer A residue and a monomer B residue as main constituent units can be obtained. The polyester copolymer that is produced is referred to as "macromer".

As the ester bond-forming monomer, the same ones as those described above can be used, and preferable combinations and the like are also in accordance with the above description.

The randomness of the distribution of the monomer residues constituting the polyester copolymer having two kinds of ester bond-forming monomer residues as the main constituent units changes depending on the difference in the reactivity of the monomers during polymerization. That is, at the time of polymerization, if one of the two types of monomers is followed by the same monomer and the other monomer with the same probability, a copolymer in which the monomer residues are completely randomly distributed can be obtained. However, if either monomer tends to bond after one monomer, a gradient copolymer with a biased distribution of monomer residues can be obtained. In the obtained gradient copolymer, the composition of the monomer residues is continuously changed from the polymerization initiation end to the polymerization termination end along the molecular chain.

Here, assuming that the monomer A is a monomer having a higher initial polymerization rate than the monomer B, when the monomer A and the monomer B are copolymerized in the macromer synthesis step, the monomer A is likely to be bonded after the monomer A. Therefore, in the synthesized macromer, a gradient structure having a composition gradient in which the ratio of the monomer A unit gradually decreases from the polymerization start end to the polymerization end end is formed. That is, the macromer obtained in this step becomes a macromer having a gradient structure in which the monomer A residue and the monomer B residue form a composition gradient in the skeleton due to the difference in the initial polymerization rate between the monomer A and the monomer B. That is, by using the monomers A and B having different initial polymerization rates in this step, a macromer having a gradient structure having a composition gradient in the skeleton can be obtained. Such a macromer may be referred to as a "gradient macromer" in the present specification.

In the macromer synthesis step, in order to realize such a gradient structure, it is desirable to synthesize macromer by a polymerization reaction occurring in one direction from the start terminal. As such a synthetic reaction, it is preferable to use ring-opening polymerization or living polymerization.

The macromer obtained in this step has an R value similar to that of the polyester copolymer in order to facilitate the production of a polyester copolymer finally satisfying the above-mentioned R value, that is, the following formula R = [AB] / (2 [2 [ A] [B]) x 100
[A]: Mole fraction (%) of monomer A residue in macromer
[B]: Mole fraction (%) of monomer B residue in macromer
[AB]: Mole fraction (%) of the structure (AB, and BA) in which the monomer A residue and the monomer B residue are adjacent to each other in the macromer.
The R value represented by is preferably 0.45 or more and 0.99 or less, and more preferably 0.50 or more and 0.80 or less.

The weight average molecular weight of the macromer synthesized in the macromer synthesis step is preferably 10,000 or more, more preferably 20,000 or more. Further, in order to suppress crystallinity and maintain flexibility, it is preferably 150,000 or less, and more preferably 100,000 or less.

[Multi-layering process]
In the mulching step, the macromers obtained in the macromer synthesis step are linked to each other, or the monomer A and the monomer B are additionally added to the macromer solution obtained in the macromer synthesis step to perform mulching. In this step, macromers obtained in one macromer synthesis step may be linked to each other, or a plurality of macromers obtained in two or more macromer synthesis steps may be linked. In addition, "multi-layering" is to form a structure in which a plurality of molecular chains having a gradient structure having a composition gradient in the skeleton of the monomer A residue and the monomer B residue are repeated by any of these methods. Means.

The number of macromer units to be mulched may be 2 or more, but if the number of linkages is large, the effect of improving the tensile strength due to the entanglement of molecular chains is obtained, so 3 or more is preferable, and 4 or more is preferable. More preferably, it is more preferably 6 or more. On the other hand, if the molecular weight of the polyester copolymer is excessively increased as a result, there is a concern that the increase in viscosity may adversely affect the moldability. Therefore, the number of macromer units is preferably 80 or less, more preferably 40 or less. , 20 or less is more preferable.

The number of linkages in macromer units can be adjusted by the catalyst used in the mulching process and the reaction time. When mulching is performed by connecting macromers to each other, the number of macromer units can be obtained by dividing the weight average molecular weight of the finally obtained polyester copolymer by the weight average molecular weight of macromers.

The polyester copolymer of the present invention may be a linear polymer in which macromer units are linearly linked, or may be a branched chain polymer in which macromer units are branched and linked.

The linear polyester copolymer can be synthesized, for example, by binding one molecule of the same gradient macromer to both ends of the gradient macromer via the ends.

When the gradient macromer has a hydroxyl group and a carboxyl group at each terminal, the ends are condensed with a condensing agent to obtain a mulched polyester copolymer. As the condensing agent, p-toluenesulfonate 4,4-dimethylaminopyridinium, 1- [3- (dimethylamino) propyl] -3-ethylcarbodiimide, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride , N, N'-dicyclohexylcarbodiimide, N, N'-diisopropylcarbodiimide, N, N'-carbonyldiimidazole, 1,1'-carbonyldi (1,2,4-triazole), 4- (4,6-) Dimethoxy-1,3,5-triazine-2-yl) -4-methylmorpholinium = chloride n hydrate, trifluoromethanesulfonic acid (4,6-dimethoxy-1,3,5-triazine-2-yl) )-(2-Octoxi-2-oxoethyl) dimethylammonium, 1H-benzotriazole-1-yloxytris (dimethylamino) phosphonium hexafluorophosphate, 1H-benzotriazole-1-yloxytripyrrolidinophosphonium Hexafluorophosphate, (7-azabenzotriazole-1-yloxy) tripyrrolidinophosphonium hexafluorophosphate, chlorotripyrrolidinophosphonium hexafluorophosphate, bromotris (dimethylamino) phosphonium hexafluorophosphate Salt, 3- (diethoxyphosphoryloxy) -1,2,3-benzotriazine-4 (3H) -one, O- (benzotriazole-1-yl) -N, N, N', N'-tetramethyl Uronium hexafluorophosphate, O- (7-azabenzotriazole-1-yl) -N, N, N', N'-tetramethyluronium hexafluorophosphate, O- (N-succinimidyl)- N, N, N', N'-tetramethyluronium tetrafluoroborate, O- (N-succinimidyl) -N, N, N', N'-tetramethyluronium hexafluorophosphate, O- (3,4-Dihydro-4-oxo-1,2,3-benzotriazine-3-yl) -N, N, N', N'-tetramethyluronium tetrafluoroborate, S- (1- (1- Oxid-2-pyridyl) -N, N, N', N'-tetramethylthiuronium tetrafluoroborate, O- [2-oxo-1 (2H) -pyridyl] -N, N, N', N'-Tetramethyluronium Tetrafluoroborate, {{[(1-cyano-2-ethoxy-2-oxoethylidene) amino] oxy} -4-morpholinomethylene} dimethylammonium Hexafluorophosphate, 2-chloro-1,3-dimethylimidazolinium hexafluorophosphate, 1- (chloro-1-pyrrolidinylmethylene) pyrrolidinium hexafluorophosphate, 2-fluoro-1 , 3-Dimethylimidazolinium hexafluorophosphate, fluoro-N, N, N', N'-tetramethylformamidinium hexafluorophosphate and the like can be used.

Further, when the polymerization reaction has a living property, that is, when the polymerization reaction can be continuously started from the end of the polymer, the monomer A and the monomer B are additionally added to the gradient macromer solution after the polymerization reaction is completed. By repeating the operation, it can be multi-layered.

Alternatively, the gradient macromers may be mulched via a linker as long as they do not affect the mechanical properties of the polymer. In particular, a linker having multiple carboxyl groups and / or multiple hydroxy groups, for example 2,2-bis (hydroxymethyl) propionic acid, is used to synthesize a branched polyester copolymer in which the linker is a branch point. Can be done.

The polyester copolymer obtained by the above-mentioned production method is a copolymer having a structure in which a monomer A residue and a monomer B residue are linked by two or more macromer units having a composition gradient in the skeleton, which is the present invention. This is a preferred embodiment of the polyester copolymer. In the present specification, such a structure may be referred to as "multi-gradient" for convenience, and a copolymer having a multi-gradient structure may be referred to as "multi-gradient copolymer".

That is, the polyester copolymer of the present invention is preferably a multi-gradient copolymer, and the multi-gradient copolymer has two macromer units having a gradient structure in which the monomer A residue and the monomer B residue form a composition gradient in the skeleton. It is preferable to have a structure in which the above is connected, and it is more preferable to have a structure in which three or more are connected. The upper limit of the number of linked macromer units having a gradient structure in which the monomer A residue and the monomer B residue form a composition gradient in the skeleton is preferably 80 or less, more preferably 40 or less, and 20 or less. The following is more preferable.

As described above, a polyester copolymer in which the monomer A residue is a lactic acid residue and the monomer B residue is a caprolactone residue is a particularly preferable embodiment of the present invention. Such a polyester copolymer is preferably produced by the following production method.

First, in the macromer synthesis step, dilactide and ε-caprolactone are polymerized in the presence of a catalyst. Dilactide, ε-caprolactone monomer, is preferably purified to remove impurities prior to use. Purification of dilactide is possible, for example, by recrystallization from toluene dried with sodium. ε- caprolactone, for example, purified by vacuum distillation under _{N 2} from CaH _2.

As a catalyst in the macromer synthesis step having a lactic acid residue and a caprolactone residue, a polyester polymerization catalyst such as an ordinary germanium-based, titanium-based, antimony-based, or tin-based catalyst can be used. Specific examples of such a polyester polymerization catalyst include tin octylate, antimony trifluoride, zinc powder, dibutyltin oxide, and tin oxalate. The method of adding the catalyst to the reaction system is not particularly limited, but it is preferably a method of adding the catalyst in a state of being dispersed in the raw material at the time of charging the raw material or in a state of being dispersed in the raw material at the start of depressurization. The amount of the catalyst used is 0.01 to 3% by weight, more preferably 0.05 to 1.5% by weight, in terms of metal atoms, based on the total amount of the monomers used.

Macromers with lactic acid residues and caprolactone residues can be obtained by placing dilactide, caprolactone and the catalyst in a reaction vessel equipped with a stirrer and reacting at 120-250 ° C. under a nitrogen stream. When water is used as the co-initiator, it is preferable to carry out a co-catalytic reaction at around 90 ° C. prior to the polymerization reaction. The reaction time is preferably 2 hours or longer, preferably 4 hours or longer, and more preferably a longer time, for example, 8 hours or longer in order to increase the degree of polymerization. However, if the reaction is carried out for an excessively long time, a problem of coloration of the polymer will occur, so 3 to 30 hours is preferable.

Next, in the mulching step, the ends of the gradient macromer having a lactic acid residue and a caprolactone residue are connected to each other by a condensation reaction to mulch. The reaction temperature of the condensation reaction is preferably 10 to 100 ° C, more preferably 20 to 50 ° C. The reaction time is preferably 1 day or longer, more preferably 2 days or longer. However, if the reaction is carried out for a long time, a problem of coloration of the polymer will occur, so 2 to 4 days is preferable.

The polyester copolymer of the present invention is a polyester copolymer having a structure in which two or more macromer units are linked, and the rate of which the initial polymerization rate is faster is V _X and the rate of which the initial polymerization rate is slower in monomer A or monomer B. When the rate is V _Y , the macromer unit is preferably a polyester copolymer having a monomer A residue and a monomer B residue satisfying _{1.1 ≤ V X} / V _{Y ≤ 40 as main constituent units.} 1.1 The polyester copolymer of the present invention having a structure in which two or more macromer units composed of a polyester copolymer having a monomer A residue and a monomer B residue satisfying _{≦ V X} / V _{Y ≦ 40 are connected as main constituent units.} Therefore, the macromer unit of the gradient structure can be obtained, and as a result, the polyester copolymer of the present invention has a multi-gradient structure, which is preferable.

In the present specification, macromer refers to a polyester copolymer obtained in the above-mentioned macromer synthesis step, and is expressed as macromer because it is a polyester copolymer for use in the above-mentioned mulching step after the macromer synthesis step. The macromer unit refers to a portion consisting of one macromonomer in the molecular chain of the polyester copolymer. For example, when two macromers are linked to form a polyester copolymer, the polyester copolymer is a polyester copolymer having a structure in which two macromers are linked.

Further, the two types of monomer residues in the macromer unit are defined as the "main constituent unit", which means that the sum of the numbers of the two types of monomer residues is included in the entire macromer unit including the other monomer residues. When the sum of the number of monomer residues in the above is 100%, it is 50 mol% or more, and when the sum of all the monomer residues of each residue contained in the entire macromer unit is 100%, it is 20. It means that it is more than mol%. For example, the main constituent unit is a monomer A residue and a monomer B residue, which means that the sum of the number of residues of the monomer A residue and the monomer B residue is included in the entire macromer unit. When the sum of the numbers is 100%, it means that it is 50 mol% or more, the monomer A residue is 20 mol% or more, and the monomer B residue is 20 mol% or more. Here, the mole fraction of the monomer A residue, the monomer B residue, and other residues can be determined from the area value of the signal derived from each residue by nuclear magnetic resonance (NMR) measurement. For example, when the monomer A residue is a lactic acid residue and the monomer B residue is a caprolactone residue, the measurement can be performed by the method described in Measurement Example 1 described later.

Here, in the monomer A or the monomer B, V _{X , which is the faster initial polymerization rate, and V Y} , which is the slower initial polymerization rate, are obtained by the following methods. Monomer A and monomer B are mixed equimolarally, and if necessary, a solvent and a catalyst are added, and the polyester copolymer is finally synthesized or is to be synthesized. Conditions such as temperature are adjusted so that the R value is obtained, and the polymerization reaction is started. Sampling is periodically performed from the sample being polymerized, and the remaining amount of the monomer A and the monomer B is measured. The remaining amount is measured, for example, by chromatography or nuclear magnetic resonance (NMR) measurement. By subtracting the remaining amount from the charged amount, the amount of the monomer used for the polymerization reaction can be obtained. When the amount of the monomer subjected to the polymerization reaction is plotted against the sampling time, the initial gradients of the curve are V _X and V _Y.

When such a monomer A and the monomer B are reacted, there is a high probability that the monomer A will be bonded to the polymer terminal during the polymerization at the initial stage of the polymerization. On the other hand, in the late stage of polymerization in which the monomer A is consumed and the concentration in the reaction solution decreases, the probability that the monomer B binds to the end of the polymer being polymerized increases. The result is a gradient polymer in which the proportion of monomer A residues gradually decreases from one end. Such a gradient polymer has low crystallinity and suppresses an increase in Young's modulus. In order to facilitate the formation of such a gradient structure, V _X / V _Y is more preferably 1.3 or more, and even more preferably 1.5 or more. On the other hand, if the difference in the polymerization rates between the monomer A and the monomer B is too large, the structure is similar to that of the block polymer in which the monomer B is polymerized after only the monomer A is polymerized, and the crystallinity is increased, which may lead to an increase in Young's modulus. Therefore, V _X / V _Y is more preferably 30 or less, further preferably 20 or less, and even more preferably 10 or less.

Preferred combinations of such monomer A and monomer B include dilactide and ε-caprolactone, glycolide and ε-caprolactone, glycolide and dilactide, dilactide and dioxepanone, ethylene oxalate and dilactide, dilactide and δ-valerolactone, and glycolide. δ-Valerolactone can be mentioned.

The polyester copolymer of the present invention preferably has a hysteresis loss change rate of 80% or less, more preferably 60% or less, and even more preferably 40% or less. Hysteresis loss refers to the area surrounded by the stretching process and the contraction process in the displacement-stress curve obtained in the tensile test as in Measurement Example 4, and corresponds to the energy lost by stretching. The rate of change in hysteresis loss is defined as a value obtained by dividing the difference between the hysteresis loss in the second cycle and the hysteresis loss in the 30th cycle by the hysteresis loss in the second cycle in the tensile test as in Measurement Example 4. When the rate of change in hysteresis loss is small, it means that the change in the polymer structure due to repeated stretching is small, that is, it means that the polyester copolymer has excellent durability.

In the present invention, the molded body refers to an object molded into various shapes by a conventional method according to a purpose. For example, a film-like body (membrane, film, sheet), a plate-like body (board), a rod-like body (rod), a tubular body (pipe, tube), a filamentous body (filament), a net-like body (mesh), a bag-like body. , Woven cloth, non-woven fabric and the like. The medical molded product is the above-mentioned molded product used for medical purposes. Medical applications include, but are not limited to, the DDS field such as sutures, artificial bones, artificial skins, wound dressings, microcapsules, and scaffolding materials for tissue and organ regeneration. The polyester copolymer of the present invention can be suitably used as a medical molded article. That is, the medical molded product of the present invention is a molded product made of the polyester copolymer of the present invention.

In the present invention, the filament refers to a filamentous body, that is, a filamentous molded body as described above. The filament is used in the state of a multifilament in which a plurality of filaments are twisted into one thread or a monofilament in which one filament is formed into one thread. The filament of the present invention is a filament made of the polyester copolymer of the present invention.

The polyester copolymer of the present invention is also used for 3D printer applications.

Hereinafter, the present invention will be described in detail with reference to Examples and Comparative Examples, but the present invention is not limited thereto.

(Measurement Example 1: Measurement of mole fraction and R value of each residue by nuclear magnetic resonance (NMR))
The purified polyester copolymer was dissolved in deuterated chloroform and ^{measured by 1} H-NMR to calculate the ratio of the lactic acid monomer residue and the caprolactone monomer residue in the polyester copolymer, respectively. ^{Further, 1} by H homo spin decoupling method, (near 5.10Ppm) methine group of lactic acid, (around 2.35 ppm) alpha-methylene group of caprolactone, the ε methylene group (around 4.10 ppm), monomeric adjacent residues Was separated by a signal derived from lactic acid or caprolactone, and the peak area of each was quantified. When δ-valerolactone is used instead of ε-caprolactone, the methine group of lactic acid (around 5.10 ppm), the α-methylene group of valerolactone (around 2.35 ppm), and the δ-methylene group (around 4.10 ppm) are similarly used. The adjacent monomer residues were separated by a signal derived from lactic acid or valerolactone, and the peak areas of each were quantified.

From each peak area ratio, [AB] of Equation 1 was calculated and the R value was calculated. Here, [AB] is a mole fraction of a structure in which a lactic acid residue and a caprolactone residue or a valerolactone residue are adjacent to each other, and specifically, AA, AB, BA, BB. It is the ratio of the number of AB and BA to the total number of. The results are shown in Tables 1 and 2.
Device name: JNM-ECZ400R (manufactured by JEOL Ltd.)
¹ H homospin decoupling irradiation position: 1.66 ppm
Solvent: Deuterated chloroform Measurement temperature: Room temperature

(Measurement Example 2: Measurement of Weight Average Molecular Weight by Gel Permeation Chromatography (GPC))
Device name: Prominence (manufactured by Shimadzu Corporation)
Mobile phase: Chloroform (for HPLC) (manufactured by Wako Pure Chemical Industries, Ltd.)
Flow rate: 1 mL / min
Column: TSKgel GMHHR-M (φ7.8mmX300mm; manufactured by Tosoh Corporation)
Detector: UV (254nm), RI
Column, detector temperature: 35 ° C
Standard substance: Polystyrene Purified polyester copolymer is dissolved in chloroform, passed through a 0.45 μm syringe filter (DISMIC-13HP; manufactured by ADVANTEC) to remove impurities, etc., and then measured by GPC, and the weight average of the polyester copolymer is measured. The molecular weight was calculated. The results are shown in Tables 1 and 2.

(Measurement Example 3: Measurement of Crystal Amount by Wide-angle X-ray Scattering (WAXS))
The purified polyester copolymer is dried under reduced pressure, dissolved in chloroform to a concentration of 5% by weight, the solution is transferred onto a "Teflon (registered trademark)" petri dish, and dried at normal pressure and room temperature for 24 days and night. I let you. This was dried under reduced pressure at 50 ° C. for 24 hours to obtain a polyester copolymer film.

The obtained polyester copolymer film (thickness of about 0.2 mm) was cut into strips (50 mm × 5 mm), and WAXS measurement was performed under the following conditions. The film was stretched using a small tensile tester (Stency) manufactured by AcroEdge, and the WAXS measurement of the unstretched film installed in the small tensile tester and the film stretched to just before breaking by the small tensile tester was performed. The obtained data was analyzed as follows, and the amount of crystals derived from monomer A was determined.

From the obtained scattering image, a graph of horizontal axis 2θ and vertical axis scattering intensity was created. For the images with orientation, the graph was created so as to include the part with the highest intensity. The obtained graph was subjected to fitting analysis, divided into peaks, and the area of the crystal peaks derived from monomer A (or the sum total if there are a plurality of high-intensity peaks) was taken as the amount of crystals derived from monomer A. (However, even if the same sample is measured, the value of 2θ differs depending on the camera length, so it is better to measure a homopolymer film consisting only of monomer A as a reference sample.) For example, when monomer A is lactic acid. The peak area near 2θ = 10, which has the highest intensity, was defined as the amount of lactic acid-derived crystals.

Measuring device: BL03XU beamline (Spring-8)
X-ray wavelength: 0.1 nm
Using the obtained crystal amount, the rate of change in the crystal amount derived from the monomer A was determined from the following formula. The results are shown in Tables 1 and 2.

Crystal Amount Change Rate = Crystal Amount at Stretching Until Immediately Before Fracture / Crystal Amount Before Stretching (immediately before fracture is a value obtained by multiplying the elongation at break by a safety factor of 0.8).

(Measurement Example 4: Measurement of breaking elongation, restoration rate, and hysteresis loss change rate by tensile test)
The purified polyester copolymer is dried under reduced pressure, dissolved in chloroform to a concentration of 5% by weight, the solution is transferred onto a "Teflon (registered trademark)" petri dish, and dried at normal pressure and room temperature for 24 days and night. I let you. This was dried under reduced pressure at 50 ° C. for 24 hours to obtain a polyester copolymer film.

The obtained polyester copolymer film (thickness: about 0.1 mm) was cut into strips (50 mm × 5 mm) and subjected to a tensile test under the following conditions according to JIS K6251 (2017). I asked for the rate. The restoration rate and the rate of change in hysteresis loss were obtained from the following equation by repeating stretching immediately before fracture, that is, to an elongation of 0.8 times the elongation at fracture, 30 times. The results are shown in Tables 1 and 2.

When marking the test piece, two markings were attached to the test piece using an appropriate marker. When marking the test piece, the test piece was not pulled, and the test piece was attached accurately and clearly at a right angle to the parallel portion of the test piece and at an equidistant distance from the center of the test piece.

Device name: EZ-1kNLX (manufactured by Shimadzu Access)
Distance between marked lines before test: 10 mm
Distance between grippers: 10 mm (grabbed the position of the marked line)
Pulling speed: 500 mm / min
Load cell: 50N
Further, the stability was stretched to just before fracture at a tensile speed of 500 mm / min to cause tensile strain (operation 1). Then, immediately after the operation 1 (that is, the shape holding time was set to 0 seconds), the tensile strain was relaxed at a speed of 500 mm / min, and the distance between the gripping tools was returned to 10 mm (operation 2). Immediately after the operation 2 (that is, the shape holding time is 0 seconds), the above-mentioned operations 1 and 2 are performed again. This was repeated, and operations 1 and 2 were performed 30 times in total, and then the stability was obtained from the following equation using the obtained values of L1 and L2. The results are shown in Table 1.

Restoration rate (%) = (L1-L2) / (L1-L0) × 100
L0: Initial length (distance between marked lines before the test)
L1: Film length at the time of stretching until just before breaking (distance between marked lines at the time of stretching until just before breaking)
L2: Film length after repeated stretching 30 times (distance between marked lines after test)
Hysteresis loss rate of change (%) = ΔD / D
D: Hysteresis loss in the 2nd cycle ΔD: Difference in hysteresis loss between the 2nd cycle and the 30th cycle

<Example 1>
50.0 g of L-lactide (PURASORB L; manufactured by PURAC) and 39.6 g of ε-caprolactone (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) are used as monomers, and 0.46 g of hydroxypivalic acid is used. It was collected in a separable flask as an initiator. 0.27 g of tin (II) octylate (Fujifilm Wako Pure Chemical Industries, Ltd.), which is a catalyst dissolved in 5.8 mL of toluene (ultra-dehydrated) (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) under an argon atmosphere. (Manufactured by Co., Ltd.) was added and reacted at 140 ° C. for 9.5 hours to obtain a crude copolymer.

The obtained crude copolymer was dissolved in 200 mL of chloroform and added dropwise to 3000 mL of hexane in a stirred state to obtain a precipitate. The precipitate was dried under reduced pressure at 50 ° C. to obtain macromer.

50 g of the macromer, 2.9 g of the catalyst, 4,4-dimethylaminopyridinium p-toluenesulfonic acid (synthetic product), and 1.2 g of 4,4-dimethylaminopyridine (Fujifilm Wako Pure Chemical Industries, Ltd.) Made) was collected. Under an argon atmosphere, these are dissolved in 200 mL of dichloromethane (dehydrated) (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), and 2.4 mL of diisopropylcarbodiimide (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), which is a condensing agent, is added. It was added and condensed and polymerized overnight at room temperature.

The reaction mixture was diluted with 220 mL of chloroform, 470 mL of 0.5 M hydrochloric acid was added, the mixture was stirred for 30 minutes, and the aqueous layer was removed by decantation. Then, 470 mL of ion-exchanged water was added, and the mixture was stirred for 10 minutes, and the step of removing the aqueous layer by decantation was repeated until the pH of the removed aqueous layer became 7. The remaining organic layer was added dropwise to 2200 mL of methanol in a stirred state to obtain a precipitate. The precipitate was dried under reduced pressure at 50 ° C. to obtain the purified polyester copolymer of Example 1.

<Example 2>
60.0 g of L-lactide (PURASORB L; manufactured by PURAC) and 31.7 g of ε-caprolactone (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) are used as monomers, and 0.46 g of hydroxypivalic acid is used. It was collected in a separable flask as an initiator. 0.27 g of tin (II) octylate (Fujifilm Wako Pure Chemical Industries, Ltd.), which is a catalyst dissolved in 5.8 mL of toluene (ultra-dehydrated) (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) under an argon atmosphere. (Manufactured by Co., Ltd.) was added and reacted at 140 ° C. for 9.5 hours to obtain a crude copolymer.

The obtained crude copolymer was dissolved in 200 mL of chloroform and added dropwise to 3000 mL of hexane in a stirred state to obtain a precipitate. The precipitate was dried under reduced pressure at 50 ° C. to obtain macromer.

50 g of the macromer, 2.1 g of the catalyst, 4,4-dimethylaminopyridinium p-toluenesulfonic acid (synthetic product), and 0.87 g of 4,4-dimethylaminopyridine (Fujifilm Wako Pure Chemical Industries, Ltd.) Made) was collected. Under an argon atmosphere, these are dissolved in 200 mL of dichloromethane (dehydrated) (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), and 1.7 mL of the condensing agent diisopropylcarbodiimide (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) is added. It was added and condensed and polymerized overnight at room temperature.

The reaction mixture was diluted with 220 mL of chloroform, 470 mL of 0.5 M hydrochloric acid was added, the mixture was stirred for 30 minutes, and the aqueous layer was removed by decantation. Then, 470 mL of ion-exchanged water was added, and the mixture was stirred for 10 minutes, and the step of removing the aqueous layer by decantation was repeated until the pH of the removed aqueous layer became 7. The remaining organic layer was added dropwise to 2200 mL of methanol in a stirred state to obtain a precipitate. The precipitate was dried under reduced pressure at 50 ° C. to obtain the purified polyester copolymer of Example 2.

<Example 3>
The amount of hydroxypivalic acid is 0.17 g, the amount of p-toluenesulfonic acid 4,4-dimethylaminopyridinium is 3.6 g, the amount of 4,4-dimethylaminopyridine is 0.37 g, and the amount of diisopropylcarbodiimide is 1. The synthesis was carried out in the same manner as in Example 1 except that it was changed to .4 mL to obtain a purified polyester copolymer of Example 3.

<Example 4>
The amount of hydroxypivalic acid was 0.45 g, the reaction temperature for obtaining a crude copolymer was 150 ° C., the amount of p-toluenesulfonic acid 4,4-dimethylaminopyridinium was 2.1 g, and 4,4-dimethylaminopyridine. The synthesis was carried out in the same manner as in Example 1 except that the amount was changed to 0.87 g and the amount of diisopropylcarbodiimide was changed to 1.7 mL, to obtain a purified polyester copolymer of Example 4.

<Comparative Example 1>
50.0 g of L-lactide (PURASORB L; manufactured by PURAC) and 39.6 g of ε-caprolactone (manufactured by Wako Pure Chemical Industries, Ltd.) as a monomer and 0.036 g of octanol as an initiator. , Collected in a separable flask. 0.27 g of tin (II) octylate (Fujifilm Wako Pure Chemical Industries, Ltd.), which is a catalyst dissolved in 5.8 mL of toluene (ultra-dehydrated) (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) under an argon atmosphere. (Manufactured by Co., Ltd.) was added and reacted at 140 ° C. for 24 hours to obtain a crude copolymer.

The obtained crude copolymer was dissolved in 200 mL of chloroform and added dropwise to 3000 mL of hexane in a stirred state to obtain a precipitate. The precipitate was dried under reduced pressure at 50 ° C. to obtain a polyester copolymer of Comparative Example 1.

<Comparative Example 2>
The synthesis was carried out in the same manner as in Example 1 except that the amount of p-toluenesulfonic acid 4,4-dimethylaminopyridinium was changed to 1.5 g and the amount of diisopropylcarbodiimide was changed to 1.2 mL, and the purification of Comparative Example 2 was carried out. A polyester copolymer was obtained.

<Comparative Example 3>
100.0 g of L-lactide (PURASORB L; manufactured by PURAC) was collected in a separable flask using 0.46 g of hydroxypivalic acid as an initiator as a monomer. 0.27 g of tin (II) octylate (Fujifilm Wako Pure Chemical Industries, Ltd.), which is a catalyst dissolved in 5.8 mL of toluene (ultra-dehydrated) (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) under an argon atmosphere. (Manufactured by Co., Ltd.) was added and reacted at 140 ° C. for 9.5 hours to obtain a crude copolymer.

The obtained crude copolymer was dissolved in 200 mL of chloroform and added dropwise to 3000 mL of hexane in a stirred state to obtain a precipitate. The precipitate was dried under reduced pressure at 50 ° C. to obtain PLA macromer.

Further, 79.2 g of ε-caprolactone (manufactured by Wako Pure Chemical Industries, Ltd.) was collected in a separable flask using 0.46 g of hydroxypivalic acid as an initiator as a monomer. 0.27 g of tin (II) octylate (Fujifilm Wako Pure Chemical Industries, Ltd.), which is a catalyst dissolved in 5.8 mL of toluene (ultra-dehydrated) (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) under an argon atmosphere. (Manufactured by Co., Ltd.) was added and reacted at 140 ° C. for 9.5 hours to obtain a crude copolymer.

The obtained crude copolymer was dissolved in 200 mL of chloroform and added dropwise to 3000 mL of hexane in a stirred state to obtain a precipitate. The precipitate was dried under reduced pressure at 50 ° C. to obtain PCL macromer.
27.9 g of the PLA macromer, 22.1 g of the PCL macromer, 2.9 g of the catalyst, 4,4-dimethylaminopyridinium p-toluenesulfonic acid (synthetic product), and 1.2 g of 4,4-dimethylamino. Ppyridine (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) was collected. Under an argon atmosphere, these are dissolved in 200 mL of dichloromethane (dehydrated) (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), and 2.4 mL of diisopropylcarbodiimide (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), which is a condensing agent, is added. It was added and condensed and polymerized overnight at room temperature.

The reaction mixture was diluted with 220 mL of chloroform, 470 mL of 0.5 M hydrochloric acid was added, the mixture was stirred for 30 minutes, and the aqueous layer was removed by decantation. Then, 470 mL of ion-exchanged water was added, and the mixture was stirred for 10 minutes, and the step of removing the aqueous layer by decantation was repeated until the pH of the removed aqueous layer became 7. The remaining organic layer was added dropwise to 2200 mL of methanol in a stirred state to obtain a precipitate. This precipitate was dried under reduced pressure at 50 ° C. to obtain a purified polyester copolymer of Comparative Example 3.

<Comparative Example 4>
50.0 g of L-lactide (PURASORB L; manufactured by PURAC) and 39.6 g of ε-caprolactone (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) are used as monomers, and 0.46 g of hydroxypivalic acid is used. It was collected in a separable flask as an initiator. 0.27 g of tin (II) octylate (Fujifilm Wako Pure Chemical Industries, Ltd.), which is a catalyst dissolved in 5.8 mL of toluene (ultra-dehydrated) (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) under an argon atmosphere. (Manufactured by Co., Ltd.) was added and reacted at 140 ° C. for 9.5 hours to obtain a crude copolymer.

The obtained crude copolymer was dissolved in 200 mL of chloroform and added dropwise to 3000 mL of hexane in a stirred state to obtain a precipitate. The precipitate was dried under reduced pressure at 50 ° C. to obtain macromer. This macromer was used as the purified polyester copolymer of Comparative Example 4.

Tables 1 and 2 show various measurement results of the polyester copolymers obtained in Examples 1 to 4 and Comparative Examples 1 to 4.

The monomer A residue ratio in the table indicates the molar ratio of the monomer A residue to 100% of the total number of moles of the monomer A residue and the monomer B residue.

Specific uses of the polyester copolymer of the present invention include non-woven fabrics for fibers, disposable toiletry products and cosmetics for containers, packaging films, agricultural multi-films, tapes and the like for films. Other medical uses include sutures, artificial bones, artificial skins, wound dressings, DDS fields such as microcapsules, and scaffolding materials for tissue and organ regeneration. Further, other toners, binders for thermal transfer inks, and the like can be considered, but the use is not limited thereto.

Claims (12)

A polyester copolymer containing two types of ester bond-forming monomer residues as main constituent units and containing no hydrophilic segment in the molecular chain.
When the two types of ester bond-forming monomers are Monomer A and Monomer B, respectively, the crystal amount change rate represented by the following formula derived from Monomer A is 0.30 to 10.00, and the crystal amount of the polyester copolymer is Rate of change = Amount of crystals when stretched to just before breaking / Amount of crystals before stretching The monomers A and B are lactic acid, glycolic acid, hydroxybutyric acid, hydroxyvaleric acid, hydroxypentanoic acid, hydroxycaproic acid, hydroxyheptanic acid, caprolactone, dioxepanone, ethylene oxalate, dioxanone, 1,4-dioxane-2. , 3-Dione, trimethylene carbonate, β-propiolactone, δ-valerolactone, β-propiolactone, β-butyrolactone, γ-butyrolactone, pivalolactone, dilactide, glycolide, and tetramethylglycolide. The polyester copolymer according to claim 1, which is a compound. The polyester copolymer according to claim 1 or 2, wherein the monomer A is lactic acid or glycolic acid. The polyester copolymer according to any one of claims 1 to 3, wherein the monomer B is caprolactone or δ-valerolactone. The polyester copolymer according to any one of claims 1 to 4, wherein the mass ratio of the hydrophilic monomer residue to the total mass of the polyester copolymer is 5% or less. The polyester copolymer according to any one of claims 1 to 5, which comprises only the monomer A residue and the monomer B residue. A polyester copolymer having a structure in which two or more macromer units are linked.
In the monomer A or the monomer B, when the rate with the faster initial polymerization rate is V _X and the rate with the slower initial polymerization rate is V _Y , the macromer unit is 1.1 ≦ V _X / V. The polyester copolymer according to any one of claims 1 to 6, wherein the monomer A residue and the monomer B residue satisfying _{Y ≤ 40 are the main constituent units.} The polyester copolymer according to any one of claims 1 to 7, wherein the molar ratio of the monomer A residue to the total number of moles of the monomer A residue and the monomer B residue is 20 to 80%. The polyester copolymer according to any one of claims 1 to 8, wherein the R value represented by the following formula is 0.45 to 0.99.
R = [AB] / 2 [A] [B] x 100
[A]: Mole fraction (%) of monomer A residue
[B]: Mole fraction (%) of monomer B residue
[AB]: Mole fraction (%) of the structure (AB and BA) in which the monomer A residue and the monomer B residue are adjacent to each other. The polyester copolymer according to any one of claims 1 to 9, wherein the weight average molecular weight is 100,000 to 1,000,000. A medical molded product made of the polyester copolymer according to any one of claims 1 to 10. A filament made of the polyester copolymer according to any one of claims 1 to 10.