JPH0718063A - Degradable polymer - Google Patents

Abstract

PURPOSE:To obtain through direct condensation with dehydration a polymer which has a reduced impurity content and is transparent and pliable, and provide a high-mol. polymer from which a molding, e.g. film or fiber, having sufficient strength is formed. CONSTITUTION:The polymer is a lactic acid/glycolic acid copolymer obtained by condensing the acids or oligomers thereof with dehydration in an organic solvent substantially in the absence of water. It has a weight-average mol.wt. of about 50,000 or greater.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a copolymer of lactic acid and glycolic acid, which is a biodegradable polymer useful as a substitute for medical materials and general-purpose resins. In particular, it relates to a copolymer produced from lactic acid and glycolic acid by direct dehydration condensation. Lactic acid and glycolic acid are widely distributed in nature and are harmless to animals, plants, and humans, and their polymerization products, polylactic acid and polyglycolic acid, are relatively easily hydrolyzed in the presence of water, and Since it is hydrolyzed and absorbed even in the living body, it is attracting attention as a polymer that can be used for the above-mentioned applications.

[0002]

2. Description of the Related Art Polylactic acid or polyglycolic acid is
Generally, it has been obtained by ring-opening polymerization of lactide or glycolide which is a cyclic dimer of lactic acid or glycolic acid.

US Pat. No. 2,703,316 discloses that D, L-lactic acid is once oligomerized and then under reduced pressure.
Lactide was isolated at 200 to 250 ° C. and further recrystallized from ethyl acetate several times to obtain racemic lactide having a melting point of 120 ° C. or higher by ring-opening polymerization to obtain a logarithmic viscosity number (i
It is described that a poly (D, L-lactic acid) having a nherent viscosity (η) of 0.45 dl / g or more can be obtained and a tough film or yarn can be obtained. It is also stated therein that the polymer obtained from lactic acid by direct condensation is brittle and cannot be stretched.

US Pat. No. 2,758,987 discloses that an L, L-lactide having a melting point of 94 ° C. or higher obtained from L-lactic acid in a similar manner has a logarithmic viscosity number (η) of 0.4d.
A method for producing poly L-lactic acid of 1 / g or more is shown. However, the production of lactide or glycolide suitable as a polymer raw material is not economical because it requires a great deal of labor and cost such as distillation and recrystallization, and hydroxycarboxylic acid which does not form a cyclic lactone such as lactide or glycolide. This method cannot be used when copolymerizing an acid.

Further, the copolymer obtained by ring-opening polymerization of lactide and glycolide has higher reactivity of glycolide than lactide, and therefore, lactide is polymerized after polyglycolide is preferentially produced, so that a block polymer is obtained. However, there is a drawback that a copolymer having the above-mentioned property and having low solubility in a solvent can be obtained.

On the other hand, the direct polycondensation reaction of a hydroxycarboxylic acid such as lactic acid or glycolic acid is a sequential reaction similar to the esterification reaction between a dibasic acid and a polyhydric alcohol, and the molecular weight increases with the reaction time. Further, the water produced at this time has an action of lowering the molecular weight of the polycondensate by a hydrolysis action, so that it is necessary to remove the produced water out of the system by using a polyhydroxycarboxylic acid such as high-molecular-weight polylactic acid or polyglycolic acid It was needed to get the acid.

Japanese Patent Publication No. 96,12, 1984
No. 3 had a reaction temperature of 220 to 260 in the absence of a catalyst.
A technique for obtaining a polylactic acid having a molecular weight of 4,000 or more by performing a condensation reaction at a temperature of 10 ° C. and a pressure of 10 mmHg or less is disclosed.

US Pat. No. 4,273,92
No. 0 discloses a copolymer of lactic acid and glycolic acid obtained by dehydration condensation using an ion exchange resin as a catalyst and then removing the catalyst. They have substantially no catalyst and a logarithmic viscosity number (η) of 0.08. Is 0.30 dl / g and the average molecular weight is 6,000 to 35,000. However, in order to obtain a high molecular weight polymer by the above method, 1
Since a high temperature of 80 ° C. or higher is required, the polymer obtained under such conditions has problems such as being colored and containing impurities due to thermal decomposition. Furthermore, the molecular weight of the polymer obtained by these methods is also limited, and it is not possible to obtain a polymer having sufficient strength as a molded product such as a film or thread.

[0009]

DISCLOSURE OF THE INVENTION According to the present invention, a direct dehydration condensation of lactic acid and glycolic acid is carried out to obtain a lactic acid-glycolic acid-free copolymer which does not contain impurities due to thermal decomposition and overcomes the above-mentioned drawbacks of the prior art. Another object is to provide a copolymer of lactic acid and glycolic acid having a sufficient strength as a molded product such as a film or a thread.

[0010]

The present invention provides an average molecular weight of 50,000 obtained by condensing lactic acid and glycolic acid or their oligomers in an organic solvent in the substantially absence of water. Or more, or a copolymer having a logarithmic viscosity number (η) of 0.40 dl / g or more and comprising lactic acid units and glycolic acid units.

The production method for obtaining the polymer of the present invention is characterized in that the reaction of lactic acid and glycolic acid is carried out in an organic solvent, and the produced water is distilled out of the reaction system together with the organic solvent. Preferably, the heat dehydration condensation reaction of lactic acid and glycolic acid is carried out in an organic solvent, and the produced water is distilled out of the reaction system together with the organic solvent, and a water content not more than the water content dissolved in the distilled organic solvent is adjusted. The reaction is carried out while charging the reaction system with the organic solvent that it has as an additional solvent.

The organic solvent which can be used in the present invention is, for example,
Hydrocarbon solvents such as toluene, xylene, mesitylene,
Chlorobenzene, bromobenzene, iodobenzene, dichlorobenzene, 1,1,2,2-tetrachloroethane, halogen solvents such as p-chlorotoluene, ketone solvents such as 3-hexanone, acetophenone and benzophenone, dibutyl ether, Anisole, phenetole, o
-Dimethoxybenzene, p-dimethoxybenzene, 3-
Ether-based solvents such as methoxytoluene, dibenzyl ether, benzylphenyl ether and methoxynaphthalene, thioether solvents such as phenyl sulfide and thioanisole, ester-based solvents such as methyl benzoate, methyl phthalate and ethyl phthalate, diphenyl ether, or 4 Alkyl-substituted diphenyl ether such as -methyl phenyl ether, 3-methyl phenyl ether, 3-phenoxytoluene, or 4-bromophenyl ether, 4-chlorophenyl ether, 4-bromodiphenyl ether, 4-methyl-4'-bromodiphenyl ether, etc. Halogen-substituted diphenyl ether, or 4
-Methoxydiphenyl ether, 4-methoxyphenyl ether, 3-methoxyphenyl ether, alkoxy substituted diphenyl ether such as 4-methyl-4'-methoxydiphenyl ether, or diphenyl ether solvent such as dibenzofuran or cyclic diphenyl ether such as xanthene. You may mix and use. And, as the solvent, those which can be easily separated from water by separation are preferable, and particularly ether type solvents, alkyl-aryl ether type solvents and diphenyl ether type solvents are more preferable in order to obtain a polyhydroxycarboxylic acid having a high average molecular weight. -Aryl ether solvents and diphenyl ether solvents are particularly preferred.

The boiling point of the solvent of the present invention is preferably high, preferably by using a solvent having a boiling point of 180 ° C. or higher, and carrying out the reaction at a low temperature and a high degree of vacuum, the reaction can be carried out efficiently without undesired side reactions. Dehydration can proceed.

The amount of these solvents used is preferably 10 to 80% in terms of the concentration of the polymer obtained.

In the present invention, in order to distill the produced water out of the reaction system, it is preferable to carry out azeotropic distillation of the used organic solvent and water. When the amount of water contained in the organic solvent distilled by azeotropic distillation is higher than the solubility of water in the organic solvent, the water may be removed by liquid separation and then returned to the reaction system. To remove dissolved water,
It may be returned to the reaction system after treatment with a desiccant or after reducing the water content by distillation or the like. Further, a new organic solvent having a low water content may be charged in place of the organic solvent distilled by azeotropic distillation. Further, the water content of the reaction mixture can be adjusted to a predetermined value by removing the water content at the beginning of the reaction by reducing the pressure and then removing a part of the organic solvent from the reaction mixture containing the organic solvent.

In the present invention, the point is to proceed with the condensation reaction while removing water. In this embodiment, the solvent may or may not be an azeotrope with water, or it may not be separated into water. But it's okay. Further, as another embodiment, a method of preliminarily charging an excess solvent and dehydrating by simply extracting the solvent, a method of drying the reaction solvent using another solvent, and the like are also included. As a further modification, water may be removed while the reaction solvent itself remains liquid. Regarding the reaction temperature of the present invention, since the solvent is azeotropic with water, it may be carried out at a predetermined temperature even if the boiling point is lowered.

The average molecular weight of the copolymer depends on the water content of the organic solvent charged to the reaction system, and depends on the kind of the solvent, but when the solvent has a high water content of 400 to 500 ppm, the obtained polyhydroxy compound is obtained. The average molecular weight of the carboxylic acid is 15,000 to 50,000. However, it is surprising that a copolymer having an average molecular weight of 40,000 to 50,000 can be obtained by using a diphenyl ether solvent even with the above-mentioned high water content. In order to obtain a copolymer having a higher average molecular weight, it is desirable that the water content of the organic solvent to be inserted into the reaction system is low, and the organic solvent distilled by azeotropic treatment is treated with a desiccant to remove or reduce water. By returning to the reaction system or inserting a new organic solvent having a low water content, the water content to be inserted is adjusted to 50 ppm or less, whereby the average molecular weight Mw of 50,000 to 40.
10,000 copolymers can be obtained.

In the present invention, as a desiccant used for obtaining a copolymer having a high average molecular weight, molecular sieves such as molecular sieve 3A, molecular sieve 4A, molecular sieve 5A, molecular sieve 13X, alumina, silica gel, calcium chloride, Calcium sulfate, diphosphorus pentoxide, concentrated sulfuric acid, magnesium perchlorate, barium oxide, calcium oxide, potassium hydroxide, sodium hydroxide, or metal hydride such as calcium hydride, sodium hydride, lithium aluminum hydride, or , Alkali metals such as sodium, and the like. Among them, molecular sieves are preferable because they are easy to handle and regenerate.

The reaction temperature in the present invention is preferably 80 to 200 ° C., more preferably 110 to 170 ° C., in consideration of the production rate of the copolymer and the thermal decomposition rate of the produced copolymer. The condensation reaction is usually carried out at the distillation temperature of the organic solvent used under normal pressure. When an organic solvent having a high boiling point is used to keep the reaction temperature within a preferable range, the reaction may be performed under reduced pressure.

If the proportion of glycolic acid in the copolymer of the present invention is too high, the stability of the copolymer against moisture becomes low, so that it is preferably 20% or less for general use. However, it may be 20% or more when the decomposition speed is particularly required. Further, when the amount of glycolic acid in the copolymer is large, a polymer having low solubility may be precipitated in the course of the polymerization reaction in the solution to hinder the polymerization reaction, so that it is preferably 90% or less.

The lactic acid unit in the copolymer of the present invention is D-form,
Each of the L-forms may be used alone, or a mixture of the D-form and the L-form may be used.

To prepare the copolymer of the present invention, a catalyst may or may not be used, but when a catalyst is used, the reaction rate can be increased. Examples of the catalyst used include metals of Group II, III, IV and V of the periodic table, oxides thereof or salts thereof. In particular,
Zinc dust, tin dust, metals such as aluminum and magnesium,
Metal oxides such as tin oxide, antimony oxide, zinc oxide, aluminum oxide, magnesium oxide and titanium oxide, stannous chloride, stannic chloride, stannous bromide, stannic bromide, antimony fluoride, chloride Metal halides such as zinc, magnesium chloride and aluminum chloride, sulfates such as tin sulfate, zinc sulfate and aluminum sulfate, carbonates such as magnesium carbonate and zinc carbonate, tin acetate, tin octanoate, tin lactate, zinc acetate and acetic acid. Organic carboxylates such as aluminum, tin trifluoromethanesulfonate, zinc trifluoromethanesulfonate, magnesium trifluoromethanesulfonate,
Examples thereof include organic sulfonates such as tin methanesulfonate and tin p-toluenesulfonate. In addition, organic metal oxides of the above metals such as dibutyltin oxide, or metal alkoxides of the above metals such as titanium isopropoxide, or alkyl metals of the above metals such as diethylzinc, or Dowex, amberlite, etc. Examples include ion exchange resins.

The amount of lactic acid and glycolic acid to be used or their oligomers is 0.0001 to 10.
The weight% is good, and considering economic efficiency, 0.001 to 2% by weight is preferable.

The production of the copolymer of the present invention is preferably carried out in an inert gas atmosphere so that water does not enter from the outside of the system, and while carrying out replacement with an inert gas or bubbling with an inert gas. May be.

The condensation reaction of the present invention can be carried out either continuously or batchwise. Dehydration of the solvent and charging of the solvent can also be carried out by continuous operation or batch operation.

The copolymer of the present invention can be produced by reacting the water produced in the reaction with the organic solvent while distilling it out of the reaction system, but preferably the produced water is distilled out of the reaction system together with the organic solvent. It is possible to produce by reacting with an organic solvent having the same or a low water content as the water content dissolved in the distilled organic solvent into the reaction system, and a preferable example of the embodiment is a raw material monomer. As described below, 90% L-lactic acid (almost all the balance is water) and 70% glycolic acid were used so that the ratio of lactic acid and glycolic acid was 1: 1.

Water separator (eg Dean Stark
trap) in a reactor equipped with a solvent and a predetermined amount of 90
% L-lactic acid, 70% glycolic acid and a predetermined amount of catalyst are charged, the reactor is heated, and the solvent and water are distilled off by azeotropy and introduced into a water separator. At first, a large amount of water contained in the raw material is distilled out together with the solvent. Water having a solubility higher than that of the solvent is removed with a water separator outside the system, and the solvent containing water for the solubility is
Return to the reaction system. At this stage, water contained in the raw material L-lactic acid is distilled out almost completely, and L-lactic acid and glycolic acid are oligomerized. The average molecular weight at this stage is 50
It is 0 to 1,000, and may contain a cyclic dimer (that is, lactide and / or glycolide) or may have an average molecular weight of up to about 5,000. The reaction time during this period is approximately 0.5 hours to several hours. This oligomerization reaction may be carried out in advance in another reactor without solvent, without catalyst, under reduced pressure,
You may carry out using a solvent without a catalyst. It is possible to continue the reaction while removing the water produced as the reaction proceeds at the distillation temperature of the solvent as it is, and returning the solvent saturated with water to the reaction system. However, an average molecular weight of 15,000 to 50,000 can be obtained. In order to obtain a higher molecular weight copolymer, after the water in the raw material is almost distilled, remove the water separator, attach a tube filled with a desiccant such as molecular sieve, and distill the solvent through this tube. Bring to reflux, treat distillate solvent in another reactor with desiccant and return to reactor, or charge new low water content solvent to reactor . The amount of water dissolved in the solvent is reduced to 50 ppm or less by these methods, and the reaction is continued for several tens of hours as it is. The L-lactic acid-glycolic acid copolymer has an average molecular weight of 50,000 to 400,000 depending on the kind of the solvent. Can be obtained. After the completion of the reaction, any treatment method may be used to obtain the desired copolymer. For example, methylene chloride is added to the reaction solution, which is then discharged into methanol, and the precipitated crystals are filtered and dried to obtain the desired copolymer. can get.

Various average molecular weights of the copolymer of the present invention can be obtained by changing the type of solvent, the type and amount of catalyst, the reaction temperature, the reaction time, the treatment method of the solvent distilled by azeotropic distillation and the like. But about 50,000-40
It is 10,000. The copolymer of the present invention has a higher solubility in a solvent than the copolymer obtained by ring-opening polymerization of lactide and glycolide, and when it is dissolved in a solvent together with a drug or the like to be mixed when preparing a sustained-release material to form a mixture. Has an effect on. Further, since the copolymer of the present invention can undergo a condensation reaction at a low temperature, it does not have a problem of being colored or containing impurities due to thermal decomposition. In the case of medical applications such as sustained-release materials, those having a low content of impurities are required from the viewpoint of safety.

The copolymer of the present invention is a polymer having an average molecular weight of 50,000 or more obtained by direct dehydration condensation from lactic acid and glycolic acid without using a cyclic dimer such as lactide or glycolide. It has not been known so far that a copolymer of lactic acid and glycolic acid having such a high molecular weight can be directly obtained. The high molecular weight copolymer thus obtained has sufficient strength and toughness when processed into a film, a molded product and the like, and can be used as it is for applications such as containers.
Particularly when formed into a film from the polymer produced by the production method of the present invention, the average molecular weight is 50,000 (η =
If it is less than 0.40 dl / g), the tensile strength and elongation are not sufficient, and there is a problem in using it as a film. Therefore, when used as a film, the average molecular weight of this polymer is 50, in terms of strength and elongation.
000 (η = 0.40 dl / g) or more is required, preferably 70,000 (η = 0.57 dl / g) or more, more preferably 100,000 (η = 0.78 dl / g).
Although the above average molecular weight is required, the production method of the present invention makes it possible to easily obtain a copolymer having a suitable molecular weight for use in this film. Furthermore, these high molecular weight copolymers can be subjected to secondary processing such as stretching, blowing and vacuum forming. Therefore, the copolymer of high-molecular-weight lactic acid and glycolic acid obtained by the method of the present invention can be used as a medical material or as a substitute for conventional general-purpose resins such as foams and reticulate bodies.

Further, in a conventional lactide-glycolide copolymer (hereinafter referred to as a lactide method copolymer) produced from a cyclic intermediate such as lactide or glycolide, two identical monomers are paired in the polymer. In contrast to the above-described arrangement of monomers, the copolymer obtained by the production method of the present invention has a structure in which two monomers are randomly arranged, and the physical properties exhibited by them are also different. For example, a random copolymer of L- lactic acid and glycolic acid of the present invention, in the copolymer of lactide and glycolide obtained by the lactide method, as shown in FIGS. 1 to 3, ¹³ C-NM methylene carbon of glycolic acid component
The R spectrum patterns are different, and the random copolymer of lactic acid and glycolic acid of the present invention shows two absorptions at 60.73 ppm and 60.86 ppm, whereas the lactide method copolymer has 60.74 ppm and 60.86 pp.
It shows four absorptions at m, 60.95 ppm and 61.01 ppm. A molecular weight of 50,000 (η = 0.40) which exhibits absorption different from that of the conventional lactide copolymer.
A copolymer of lactic acid and glycolic acid of dl / g) or more,
It's my first time.

This random copolymer of lactic acid and glycolic acid has practical advantages such as good heat-sealing property and is used as a packaging film. When used as a soft polymer, the amount of plasticizer used can be reduced. Further, the copolymer of lactic acid and glycolic acid of the present invention containing glycolic acid shows excellent transparency when formed into a film.

[0032]

EXAMPLES Examples will be shown below, but the present invention is not limited thereto. The average molecular weight (MW) of the polyhydroxycarboxylic acids described in this specification was determined by gel permeation chromatography (column temperature 40 ° C., chloroform solvent) in comparison with a polystyrene standard sample. The water content in the solvent was measured using a Karl Fischer water content meter (MKC-210, manufactured by Kyoto Electronics Manufacturing Co., Ltd.). In addition, the logarithmic viscosity number (η) of the copolymer of lactic acid and glycolic acid of the present invention was measured at 20 ° C. using a Ubbelohde viscometer and a solution in which 0.1 g of the copolymer was dissolved in 100 ml of methylene chloride was used. I asked. η = ln (t / t ₀ ) / C (where t is the solution outflow time, t ₀ is the solvent outflow time,
C represents the concentration of the solution (g / dl). ) In the examples,
The water content in the solvent is measured by the Karl Fischer water content meter (MKC-2
10, manufactured by Kyoto Electronics Manufacturing Co., Ltd.).

Example 1 90% L-lactic acid 36.0 g, 70% glycolic acid 9.0
g at 150 ° C./50 mmHg for 3 hours while heating and stirring while distilling water out of the system to obtain 30.8 g of an oligomer. Add 0.158g of tin powder to this, 150 ℃ / 30mmHg
Then, the mixture was stirred for another 2 hours. Dean Stark t
Attach a rap, add 0.743 g of tin powder and 95.0 g of diphenyl ether, and remove water by azeotropic dehydration reaction at 150 ° C./35 mmHg for 1 hour, and then Dean
The Stark trap was removed, a tube filled with 25 g of the molecular sieve 3A was attached, and the solvent distilled by reflux was allowed to return to the system through the molecular sieve. The reaction was carried out at 150 ° C./35 mmHg for 40 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm. 220 g of chloroform was added to this reaction solution, and suction filtration was performed to remove tin powder. The chloroform solution was washed with 100 ml of 1N hydrochloric acid, further washed twice with 100 ml of water and then discharged into 750 ml of methanol, and the precipitated solid was suction filtered, followed by washing with methanol and washing with hexane. 30 ° C / 5mmH
Copolymer of lactic acid and glycolic acid 2 after drying under reduced pressure
4.0 g (yield 85%) was obtained. The average molecular weight of the obtained copolymer was 160,000, and the glass transition temperature and melting point by differential thermal analysis were 55 ° C. and 135 ° C., respectively. The obtained polymer was subjected to ¹³ C-NMR analysis using deuterated chloroform as a solvent. The whole figure is Fi
The signal of the expanded methylene carbon of the glycolic acid component is shown in Fig. 1 and in Fig. 2. The polymers of the present invention have about 6
It has a large signal at 0.86ppm and is about 60.73.
It is characterized by having a small signal in ppm.

Comparative Example 1 194.4 g (1.35 mol) of L-lactide, 17.4 g (0.15 mol) of glycolide, 0.01% by weight of tin octoate, and 0.03% by weight of lauryl alcohol were added. It was sealed in a thick-walled cylindrical polymerization vessel made of stainless steel equipped with a stirrer, deaerated under vacuum for 2 hours, and then replaced with nitrogen gas. The mixture was heated at 200 ° C. for 5 hours with stirring under a nitrogen atmosphere. While maintaining the temperature as it was, the inside of the reaction vessel was depressurized to 3 mmHg by gradually degassing with a vacuum pump through an exhaust pipe and a glass receiver. One hour after the start of degassing, the distillation of the monomer and low-molecular-weight volatile matter disappeared, so the inside of the container was replaced with nitrogen, and the polymer was extracted from the lower part of the container into a string and pelletized to obtain white poly L-lactic acid. It was Dissolve this pellet in 2 l of chloroform,
It was washed with 1 liter of 1N hydrochloric acid, washed twice with 1 liter of water and then discharged into 7.5 liter of methanol, and the precipitated solid was suction-filtered, followed by washing with methanol and hexane. After drying under reduced pressure at 30 ° C./5 mmHg, 192.7 g (yield 91%) of a copolymer of lactic acid and glycolic acid was obtained.
The average molecular weight of the obtained copolymer was 160,000, and the glass transition temperature and melting point by differential thermal analysis were 55 ° C. and 145 ° C., respectively.

The polymer obtained was subjected to ¹³ C-NMR analysis using deuterated chloroform as a solvent. The expanded methylene carbon signal of the glycolic acid component is shown in Fig. 3.
Comparing these with the signal of the polymer obtained in Example 32, it can be seen that the pattern is significantly different. At methylene carbon, the polymer of Example 1 is about 60.86 ppm.
Has a large signal at about 60.73 ppm, while the polymer of Comparative Example 1 synthesized from lactide has about 60.76 ppm,
About 60.86ppm, about 60.95ppm, about 61.0
It has 4 signals at 1 ppm and can be easily distinguished.

Reference Example 1 The polymer having an average molecular weight of 160,000 obtained in Example 1 was dissolved in chloroform, and a 150 mm × 150 mm film was prepared from the solution by a casting method. The physical properties of the produced film are shown below. Thickness: 41 to 43 μm Tensile strength: 570 kg / cm ² (yield) 480 kg / cm ² (break) Elongation: 14% Further, two obtained films were subjected to a scissor welding test with two heating plates having a width of 5 mm. It was It was possible to perform welding by pressure bonding for 0.5 seconds at a heating plate temperature of 95 ° C. and a pressure of 0.5 kg / cm 2.

Reference Example 2 From the polymer having an average molecular weight of 160,000 obtained in Comparative Example 1, 150 mm × 150 in the same manner as in Reference Example 1.
A film of mm was obtained. The physical properties of the produced film are shown below. Thickness: 37 to 39 μm Tensile strength: 620 kg / cm ² (yield, rupture) Elongation: 7% A welding test was conducted in the same manner as in Reference Example 8 using two obtained films. As a result, the heating plate temperature 95 ℃,
Although pressure was applied for 0.5 seconds at a pressure of 0.5 kg / cm 2, welding could not be performed. To perform welding at a pressure of 0.5 kg / cm2 and a pressure bonding time of 0.5 seconds, the heating plate temperature is 110 ° C.
Was needed.

Example 2 20.0 g of 90% L-lactic acid, 70% glycolic acid 21.
Polymerization and post-treatment were carried out in the same manner as in Example 1 except that 7 g was used to obtain a copolymer of L-lactic acid and glycolic acid having an average molecular weight of 140,000. Yield 21.5 g (yield 76
%). When benzene was added to this polymer and it was left at room temperature, it easily dissolved. The glass transition temperature by differential thermal analysis was 43 ° C.

Reference Example 3 The polymer having an average molecular weight of 140,000 obtained in Example 2 was dissolved in chloroform, and a 150 mm × 150 mm film was prepared from the solution by a casting method. The physical properties of the produced film are shown below. Thickness: 58-60 μm Tensile strength: 590 kg / cm ² (yield) 370 kg / cm ² (breaking) Elongation: 36%

Comparative Example 2 Polymerization and post-treatment were carried out in the same manner as in Comparative Example 2 except that 108 g (0.75 mol) of L-lactide and 87 g (0.75 mol) of glycolide were used, and the average molecular weight was 140,000.
A copolymer of L-lactide and glycolide was obtained.
Yield 161.9 g (83% yield). Benzene was added to this polymer and left at room temperature, but it did not dissolve easily. The glass transition temperature by differential thermal analysis was 47 ° C.

Reference Example 4 The polymer having an average molecular weight of 140,000 obtained in Comparative Example 2 was dissolved in chloroform, and a 150 mm × 150 mm film was prepared from the solution by a casting method. The physical properties of the produced film are shown below. Thickness: 62-64 μm Tensile strength: 540 kg / cm ² (yield, fracture) Elongation: 7%

[0042]

The copolymer of lactic acid and glycolic acid of the present invention has a different structure from that obtained by the ring-opening polymerization of lactide and glycolide, and the results of ¹³ C-NMR and differential thermal analysis are different. In addition, the film has a large elongation, a high heat-sealing property, and a high solubility of the polymer in a solvent. In addition, it is a transparent, non-coloring polymer with few impurities, and is a safe and excellent degradable material used for medical applications, food packaging applications and the like.

[Brief description of drawings]

FIG. 1 is an overall view of a ¹³ C-NMR spectrum of a random copolymer of 90% L-lactic acid and 10% glycolic acid obtained in Example 1.

FIG. 2 is a ¹³ C-NMR spectrum of methylene carbon of a glycolic acid component of a random copolymer of L-lactic acid 90% and glycolic acid 10% obtained in Example 1.

FIG. 3 is a ¹³ C-NMR spectrum of methylene carbon of the glycolic acid component of the copolymer of 90% L-lactide and 10% glycolide obtained in Comparative Example 1.

Claims (11)

[Claims] 1. A weight average molecular weight of about 50,000 obtained by subjecting lactic acid and glycolic acid or their oligomers to dehydration condensation reaction in a reaction mixture containing an organic solvent in the substantially absence of water. The above is a copolymer. 2. A method of removing at least a part of an organic solvent from a reaction mixture, and charging the reaction mixture with an additional organic solvent having a water content less than or equal to that of the organic solvent to be removed. The copolymer according to claim 1, 3. The organic solvent removed from the reaction mixture is
The copolymer according to claim 2, which is obtained by a method of removing water by contacting with a desiccant and returning it to the reaction mixture as an additional solvent. 4. The copolymer according to claim 3, wherein the desiccant is a molecular sieve, diphosphorus pentoxide or a metal hydride. 5. The copolymer according to claim 2, wherein the water content of the organic solvent additionally charged to the reaction mixture is 50 ppm or less. 6. Copolymer according to claim 2, obtained by first azeotropically removing water from the reaction mixture and then removing part of the organic solvent from the reaction mixture. 7. The copolymer according to claim 1, wherein the organic solvent is an ether solvent. 8. The copolymer according to claim 7, wherein the ether organic solvent is anisole or phenetole. 9. The copolymer according to claim 1, wherein the organic solvent is a diphenyl ether solvent. 10. The copolymer according to claim 9, wherein the diphenyl ether solvent is diphenyl ether. 11. The copolymer according to claim 1, wherein the boiling point of the organic solvent is 180 ° C. or higher.