JP3267391B2 - Degradable polymer - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

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 by direct dehydration condensation from lactic acid and glycolic acid. Lactic acid and glycolic acid are widely distributed in nature and harmless to animals, plants and humans, and their polymers, polylactic acid and polyglycolic acid, are relatively easily hydrolyzed in the presence of water, 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.

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

US Pat. No. 2,758,987 discloses that 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 0.4 d.
A method for producing 1 / g or more of poly L-lactic acid is shown. However, the production of lactide and glycolide suitable for polymer raw materials requires enormous labor and cost such as distillation and recrystallization, and is not economical.In addition, hydroxycarboxylic acids that do not form cyclic lactones such as lactide and glycolide are not economical. This method cannot be used when copolymerizing an acid.

Further, the copolymer obtained by ring-opening polymerization of lactide and glycolide has a higher reactivity of glycolide than lactide, so that lactide is polymerized after polyglycolide is formed preferentially, so that a block polymer is formed. And a copolymer 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 like the esterification reaction between a dibasic acid and a polyhydric alcohol, and the molecular weight increases with the reaction time. In addition, since the water generated at this time has an action of reducing the molecular weight of the polycondensate by a hydrolysis action, it is necessary to remove the generated water to the outside of the system to obtain a polyhydroxycarboxylic acid such as a high molecular weight polylactic acid or polyglycolic acid. Required to get the acid.

Japanese Patent Publication No. 96,12 / 1984
No. 3 has a reaction temperature of 220 to 260 in the absence of a catalyst.
There is disclosed a technique in which a condensation reaction is performed at a temperature of 10 ° C. and a pressure of 10 mmHg or less to obtain polylactic acid having a molecular weight of 4,000 or more.

Further, US Pat. No. 4,273,92
No. 0 discloses a copolymer of lactic acid and glycolic acid obtained by removing the catalyst after dehydration condensation using an ion exchange resin as a catalyst, which contains substantially no catalyst and has a logarithmic viscosity number (η) of 0.08. 0.30 dl / g and a weight average molecular weight of 6,000 to 35,000.
However, in the above method, a high temperature of 180 ° C. or more is required to obtain a high molecular weight polymer, and the polymer obtained under such conditions has problems such as coloring and containing impurities due to thermal decomposition. Furthermore, the molecular weight of the polymer obtained by these methods is limited, and it is not possible to obtain a polymer having sufficient strength as a molded product such as a film or a thread.

[0009]

SUMMARY OF THE INVENTION The present invention provides a colorless lactic acid-glycolic acid copolymer containing no impurities due to thermal decomposition, which overcomes the above-mentioned disadvantages of the prior art, by direct dehydration condensation of lactic acid and glycolic acid. It is another object of the present invention to provide a copolymer of lactic acid and glycolic acid having sufficient strength as a molded product such as a film or a thread.

[0010]

The present invention SUMMARY OF] is a lactic acid and glycolic acid, or oligomers thereof in an organic solvent, Re obtain et by condensing in a state in which substantially no water
A copolymer comprising a lactic acid unit and a glycolic acid unit, having a weight average molecular weight of 50,000 or more, or a logarithmic viscosity number (η) of 0.40 dl / g or more.

A feature of the production method for obtaining the polymer of the present invention is that the reaction between 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, a heat dehydration condensation reaction of lactic acid and glycolic acid is performed in an organic solvent, and the generated water is distilled out of the reaction system together with the organic solvent, and the amount of water that is not more than the amount of water dissolved in the distilled organic solvent is reduced. The reaction is performed while charging the organic solvent having the organic solvent as an additional solvent into the reaction system.

The organic solvent that can be used in the present invention is, for example,
Hydrocarbon solvents such as toluene, xylene and mesitylene,
Halogen solvents such as chlorobenzene, bromobenzene, iodobenzene, dichlorobenzene, 1,1,2,2-tetrachloroethane and p-chlorotoluene; ketone solvents such as 3-hexanone, acetophenone and benzophenone; dibutyl ether; Anisole, phenetole, o
-Dimethoxybenzene, p-dimethoxybenzene, 3-
Ether solvents such as methoxytoluene, dibenzyl ether, benzylphenyl ether and methoxynaphthalene; thioether solvents such as phenyl sulfide and thioanisole; ester solvents such as methyl benzoate, methyl phthalate and ethyl phthalate; diphenyl ether; Alkyl-substituted diphenyl ethers such as -methylphenyl ether, 3-methylphenyl ether, and 3-phenoxytoluene; or 4-bromophenyl ether, 4-chlorophenyl ether, 4-bromodiphenyl ether, and 4-methyl-4'-bromodiphenyl ether. Halogen-substituted diphenyl ether, or 4
Alkoxy-substituted diphenyl ethers such as -methoxydiphenyl ether, 4-methoxyphenyl ether, 3-methoxyphenyl ether, 4-methyl-4'-methoxydiphenyl ether, or diphenyl ether solvents such as cyclic diphenyl ethers such as dibenzofuran and xanthene; May be used as a mixture. As the solvent, those which can be easily separated and separated from water are preferable. Particularly, in order to obtain a polyhydroxycarboxylic acid having a high weight average molecular weight, an ether solvent, an alkyl-
Aryl ether solvents and diphenyl ether solvents are more preferred, but alkyl-aryl ether solvents and diphenyl ether solvents are particularly preferred.

The solvent of the present invention preferably has a higher boiling point. Preferably, a solvent having a boiling point of 180 ° C. or more is used, and the reaction is carried out at a low temperature and a high degree of vacuum. Dehydration can proceed.

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

In the present invention, in order to distill the generated water out of the reaction system, it is preferable to use azeotropic distillation of the organic solvent used and water. The organic solvent distilled off by azeotropic distillation may be returned to the reaction system after removing water by liquid separation when the amount of water contained is higher than the solubility of water in the organic solvent. To remove dissolved water,
After treating with a desiccant or reducing the water content by distillation or the like, it may be returned to the reaction system. Instead of the organic solvent distilled off by azeotropic distillation, a new organic solvent having a low water content may be charged. In addition, the water content of the reaction mixture can be set to a predetermined value by removing water under reduced pressure at the beginning of the reaction and then removing a part of the organic solvent from the reaction mixture containing the organic solvent.

In the present invention, the condensation reaction is promoted while removing water. In this embodiment, the solvent may or may not be azeotropic with water, and may or may not separate from water. May be. Further, other embodiments include a method in which an excess solvent is charged in advance and dehydration is performed by simply extracting the solvent, a method in which the reaction solvent is dried using another solvent, and the like. As a further modification, moisture may be removed while the reaction solvent itself remains liquid. Regarding the reaction temperature of the present invention, since the solvent azeotropes with water, the reaction may be performed at a predetermined temperature even if the boiling point is lowered.

The weight average molecular weight of the copolymer also depends on the amount of water in the organic solvent to be charged into the reaction system, and depends on the type of the solvent. The weight average molecular weight of the hydroxycarboxylic acid is from 15,000 to 50,000. However, it is surprising that a copolymer having a weight average molecular weight of 40,000 to 50,000 can be obtained using a diphenyl ether-based solvent even at the high water content.
To obtain a copolymer having a higher weight 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 distillation is treated with a desiccant to remove or reduce water and return to the reaction system, or a new water having a low water content is used. By inserting an organic solvent to reduce the amount of water to be inserted to 50 ppm or less, the weight average molecular weight Mw is increased.
50,000-400,000 copolymers can be obtained.

In the present invention,weightHigh average molecular weight
The desiccant used to obtain the polymer is molecular
Rasheave 3A, molecular sieve 4A, molecular
-Molecular sieves such as sieve 5A and molecular sieve 13X
Lashibes, alumina, silica gel, calcium chlorideC
System, calcium sulfate, diphosphorus pentoxide, concentrated sulfuric acid, perchloric acid
Magnesium, barium oxide, calcium oxide, hydroxylated
Potassium, sodium hydroxide, or calcium hydride
, Sodium hydride, lithium aluminum hydride, etc.
Metal hydride or alkali metal such as sodium
And the like. Above all, due to ease of handling and reproduction
Molecular sieves are preferred.

The reaction temperature in the present invention is preferably from 80 to 200 ° C., more preferably from 110 to 170 ° C. in consideration of the formation rate of the copolymer and the rate of thermal decomposition of the formed copolymer. The condensation reaction is usually performed at normal pressure at the distillation temperature of the organic solvent used. When a high-boiling organic solvent is used to keep the reaction temperature in 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 large, the stability of the copolymer against water becomes low. However, if the speed of decomposition is particularly required, it may be 20% or more. In addition, when the amount of glycolic acid in the copolymer increases, a polymer having low solubility may precipitate in the course of the polymerization reaction in a solution to inhibit the polymerization reaction, and thus is preferably 90% or less.

The lactic acid unit in the copolymer of the present invention is a 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.

In preparing the copolymer of the present invention, a catalyst may or may not be used. When a catalyst is used, the reaction rate can be increased. Examples of the catalyst to be used include metals of Groups II, III, IV and V of the periodic table, oxides and salts thereof. In particular,
Metals such as zinc dust, tin dust, 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 octoate, tin lactate, zinc acetate and acetic acid Organic carboxylates such as aluminum, tin trifluoromethanesulfonate, zinc trifluoromethanesulfonate, magnesium trifluoromethanesulfonate,
Organic sulfonates such as tin methanesulfonate and tin p-toluenesulfonate are exemplified. In addition, an organic metal oxide of the above-mentioned metal such as dibutyltin oxide, or a metal alkoxide of the above-mentioned metal such as titanium isopropoxide, or an alkyl metal of the above-mentioned metal such as diethylzinc, or Dowex, Amberlite or the like Ion exchange resins and the like.

The amount of the lactic acid and glycolic acid to be used or the oligomer thereof is 0.0001 to 10%.
% By weight, and from the viewpoint of economy, 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 as to prevent moisture from entering from outside 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 by a continuous operation or a batch operation. The dehydration of the solvent and the charging of the solvent can be performed by a continuous operation or a batch operation.

The copolymer of the present invention can be produced by reacting the water produced by the reaction with the organic solvent while distilling it out of the reaction system. Preferably, the produced water is distilled out of the reaction system together with the organic solvent. And an organic solvent having the same or lower water content as that dissolved in the distilled organic solvent can be produced by reacting while charging the reaction system, and a preferred example of the embodiment is a raw material monomer. The following description is made using 90% L-lactic acid (substantially all of the remainder is water) and 70% glycolic acid so that lactic acid and glycolic acid are 1: 1.

A water separator (eg, Dean Stark)
In a reactor equipped with a trap, solvent and a predetermined amount of 90
% L-lactic acid, 70% glycolic acid, and a predetermined amount of a catalyst are charged, the reactor is heated, and the solvent and water are distilled off by azeotropic distillation and led to a water separator. At first, a large amount of water contained in the raw material is distilled off together with the solvent. Water with a solubility higher than that of the solvent is separated by a water separator and removed outside the system.
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 weight average molecular weight at this stage is
500 to 1,000, and may contain a cyclic dimer (ie, lactide and / or glycolide), or may have a weight 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, or may be carried out without solvent using a solvent. At the distillation temperature of the solvent, the water produced as the reaction proceeds is removed, and the reaction may be continued while returning the solvent saturated with water to the reaction system. Depending on the weight average molecular weight, 15,000 to 50,000 can be obtained. To obtain higher molecular weight copolymers,
After the water in the raw material is almost distilled off, remove the water separator, attach a tube filled with a desiccant such as molecular sieve, and allow the solvent to be distilled to reflux through this tube,
The distilled solvent is treated in a separate reactor containing a desiccant and returned to the reactor, or a new low water content solvent is charged to the reactor. The amount of water dissolved in the solvent by these methods 50ppm or less, by continued this state tens hours, depending on the kind of the solvent, heavy
An L-lactic acid-glycolic acid copolymer having a weight average molecular weight of 50,000 to 400,000 can be obtained. After the completion of the reaction, any method may be used to obtain the desired copolymer.For example, methylene chloride is added to the reaction solution,
Thereafter, the mixture is discharged into methanol, and the precipitated crystals are filtered and dried to obtain a desired copolymer.

The weight average molecular weight of the copolymer of the present invention is
Various types can be obtained by changing the type of solvent, the type and amount of catalyst, the reaction temperature, the reaction time, the method of treating the solvent distilled off by azeotropic distillation, and the like.
00,000. The copolymer of the present invention has higher solubility in a solvent than a copolymer obtained by ring-opening polymerization of lactide and glycolide, and may be dissolved in a solvent together with an agent to be mixed when producing a sustained-release material to form a mixture. Is effective. Further, since the copolymer of the present invention can undergo a condensation reaction at a low temperature, there is no problem such as coloring or inclusion of impurities due to thermal decomposition. In the case of a medical use such as a sustained release material, a material having a small content of impurities is required from the viewpoint of safety.

The copolymer of the present invention is obtained by directly dehydrating and condensing lactic acid and glycolic acid without using a cyclic dimer such as lactide or glycolide.
It has not been known until now that a polymer having a weight average molecular weight of 50,000 or more and a copolymer of lactic acid and glycolic acid having such a high molecular weight can be obtained directly from a monomer. The high molecular weight copolymer thus obtained has sufficient strength and toughness when processed into a film, molded product, or the like, and can be used as it is for applications such as containers. In particular, when the polymer produced by the production method of the present invention is formed into a film, the weight average molecular weight is 50,000.
If it is less than 0 (η = 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 weight average molecular weight of this polymer is required to be 50,000 (η = 0.40 dl / g) or more, and preferably 70,000 (η = 0.57 dl) in terms of strength and elongation. /
g) or more, more preferably 100,000 (η = 0.7
A weight average molecular weight of at least 8 dl / g) is required, but according to the production method of the present invention, a copolymer having a suitable molecular weight for use in this film can be easily obtained. Further, these high molecular weight copolymers can be subjected to secondary processing such as stretching, blowing and vacuum forming. Therefore, the high molecular weight copolymer of 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 a conventional general-purpose resin such as a foam or a network.

In a conventional copolymer of lactide and glycolide produced from a cyclic intermediate such as lactide or glycolide (hereinafter referred to as a lactide copolymer), two identical monomers are paired in a polymer. While the monomer sequence is constituted, the copolymer obtained by the production method of the present invention has a structure in which two monomers are randomly arranged, and they also have different physical properties. For example, in the random copolymer of L-lactic acid and glycolic acid of the present invention and the copolymer of lactide and glycolide obtained by the lactide method, as shown in FIGS. 1 to 3, ¹³ C-NM of methylene carbon of glycolic acid component
The R spectrum pattern is different. The random copolymer of lactic acid and glycolic acid of the present invention shows two absorptions at 60.73 ppm and 60.86 ppm, while the lactide copolymer has 60.74 ppm and 60.86 pp.
m, 60.95 ppm and 61.01 ppm show four absorptions. The weight average molecular weight of 50,000 (η = 50) showing absorption different from that of the copolymer obtained by the conventional lactide method.
A copolymer of lactic acid and glycolic acid of 0.40 dl / g or more is the first one.

The random copolymer of lactic acid and glycolic acid has practical advantages such as good heat sealing properties and is used as a packaging film. When used as a soft polymer, the amount of plasticizer used can be reduced. 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 to these examples. The weight average molecular weight (MW) of the polyhydroxycarboxylic acids described in the present specification was determined by gel permeation chromatography (column temperature 40 ° C,
(Chloroform solvent) in comparison with a polystyrene standard sample. The water in the solvent was measured using a Karl Fischer moisture meter (MKC-210, manufactured by Kyoto Electronics Industry Co., Ltd.). 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 using a solution in which 0.1 g of the copolymer was dissolved per 100 ml of methylene chloride. I asked. η = ln (t / t ₀ ) / C (where t is the outflow time of the solution, t ₀ is the outflow time of the solvent,
C represents the concentration of the solution (g / dl). ) In the examples,
The water in the solvent was measured using a Karl Fischer moisture meter (MKC-2).
10, Kyoto Electronics Industry Co., Ltd.).

EXAMPLE 1 36.0 g of 90% L-lactic acid, 9.0% of 70% glycolic acid
g was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 30.8 g of an oligomer. Then, 0.158 g of tin powder was added, and 150 ° C./30 mmHg was added.
And further stirred for 2 hours. Dean Stark t
rap, 0.743 g of tin powder and 95.0 g of diphenyl ether were added, and an azeotropic dehydration reaction was carried out at 150 ° C./35 mmHg for 1 hour to remove water, and then Dean
The Stark trap was removed, and a tube filled with 25 g of molecular sieve 3A was attached, so that the solvent distilled off by reflux returned to the system through the molecular sieve. The reaction was performed at 150 ° C./35 mmHg for 40 hours. The water content in the solvent after passing through the molecular sieve was 2 ppm. To this reaction solution, 220 g of chloroform was added, and suction filtration was performed to remove tin powder. This chloroform solution was washed with 1N hydrochloric acid (100 ml), further washed with water (100 ml) twice, discharged into methanol (750 ml), and the precipitated solid was filtered by suction, followed by methanol washing and hexane washing. 30 ℃ / 5mmH
g of lactic acid and glycolic acid after drying under reduced pressure.
4.0 g (85% yield) was obtained. Of the resulting copolymer
The weight average molecular weight 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 heavy chloroform as a solvent. Fig. 1 shows the overall diagram, and Fig. 2 shows the expanded signal of the methylene carbon of the glycolic acid component. The polymer of the present invention has a large signal at about 60.86 ppm,
It is characterized by having a small signal at 3 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 It was sealed in a thick cylindrical stainless steel polymerization vessel equipped with a stirrer, degassed 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 air was gradually degassed by a vacuum pump through an exhaust pipe and a glass receiver, and the pressure inside the reaction vessel was reduced to 3 mmHg. One hour after the start of degassing, the distillation of the monomer and low-molecular-weight volatiles disappeared, so the inside of the container was replaced with nitrogen, and the polymer was pulled out from the lower part of the container into a string and pelletized to obtain white poly L-lactic acid. Was. Dissolve the pellet in 2 l of chloroform,
After washing with 1 l of 1N hydrochloric acid and further washing twice with 1 l of water, the mixture was discharged into 7.5 l of methanol, and the precipitated solid was filtered by suction, followed by washing with methanol and washing with hexane. After drying under reduced pressure at 30 ° C./5 mmHg, 192.7 g (91% yield) of a copolymer of lactic acid and glycolic acid was obtained.
The weight average molecular weight of the obtained copolymer is 160,00
0 and the glass transition temperature and the melting point by differential thermal analysis were 55 ° C. and 145 ° C., respectively.

The obtained polymer was subjected to ¹³ C-NMR analysis using deuterated chloroform as a solvent. The signal of the expanded methylene carbon of the glycolic acid component is shown in FIG.
When these are compared with the signal of the polymer obtained in Example 1, it can be seen that the patterns are significantly different. At methylene carbon, the polymer of Example 1 has a large signal at about 60.86 ppm and a small signal at about 60.73 ppm, whereas the polymer of Comparative Example 1 synthesized from lactide has a signal of about 60 0.76 ppm, about 60.86 ppm, about 60.95 ppm, about 61.01
It has four signals in ppm and can be easily distinguished.

Reference Example 1 The polymer having a weight 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. Further, the obtained two films were sandwiched between two heating plates having a width of 5 mm to perform a welding test. Welding was possible by pressing at a heating plate temperature of 95 ° C. and a pressure of 0.5 kg / cm 2 for 0.5 seconds.

Reference Example 2 From the polymer having a weight average molecular weight of 160,000 obtained in Comparative Example 1, 150 mm × 1 was obtained in the same manner as in Reference Example 1.
A 50 mm film was obtained. The physical properties of the produced film are shown below. Further, a welding test was performed using the two obtained films in the same manner as in Reference Example 1 . As a result, the heating plate temperature was 95 ° C,
Pressure bonding was performed for 0.5 seconds at a pressure of 0.5 kg / cm ² , but no welding could be performed. In order to perform welding at a pressure of 0.5 kg / cm ² and a pressing time of 0.5 second, the heating plate temperature is 110 ° C.
Was needed.

Example 2 20.0 g of 90% L-lactic acid, 70% glycolic acid
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 a weight average molecular weight of 140,000. Yield 21.5 g (Yield 7
6%). Benzene was added to this polymer, and it was easily dissolved when left at room temperature. The glass transition temperature by differential thermal analysis was 43 ° C.

Reference Example 3 The polymer having a weight 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.

Comparative Example 2 Polymerization and post-treatment were conducted in the same manner as in Comparative Example 1 except that 108 g (0.75 mol) of L-lactide and 87 g (0.75 mol) of glycolide were used, and the weight average molecular weight was 140,0.
A copolymer of L-lactide and glycolide of 00 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 A polymer having a weight 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.

[0042]

The copolymer of lactic acid and glycolic acid of the present invention has a different structure from that obtained by ring-opening polymerization of lactide and glycolide, and the results of ¹³ C-NMR and differential thermal analysis are different. In addition, they are also characterized in practical aspects such as high film elongation, high heat sealability, and high solubility of the polymer in a solvent. In addition, it is a polymer with little impurities, transparent and non-colored. It is a safe and highly decomposable material used for medical applications and food packaging applications.

[Brief description of the drawings]

FIG. 1 is an overall view of 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 90% L-lactic acid and 10% glycolic acid obtained in Example 1.

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

──────────────────────────────────────────────────続 き Continued on front page (58) Field surveyed (Int. Cl. ⁷ , DB name) C08G 63/00-63/91

Claims (9)

(57) [Claims] When a dehydration-condensation reaction is carried out in a reaction mixture containing lactic acid and glycolic acid or an oligomer thereof in a substantially water-free state, a small amount of an organic solvent is removed from the reaction mixture.
Remove at least part of the organic solvent
With additional organic solvent with less or equal water content
The weight average molecular weight obtained by charging the mixture is 5
A copolymer that is greater than or equal to 000. Wherein the reaction mixture an organic solvent which is removed from the product in contact with a desiccant to remove water, copolymer of claim 1, wherein obtained by the process returned to the reaction mixture as an additional solvent. 3. The copolymer according to claim 2 , wherein the desiccant is a molecular sieve, diphosphorus pentoxide or a hydrogen metal compound. Wherein the organic solvent is an ether solvent, or diphenyl ether solvents copolymer of claim 1, wherein. 5. The copolymer according to claim 4 , wherein the ether solvent is anisole or phenetole. 6. The copolymer according to claim 4, wherein the diphenyl ether solvent is diphenyl ether. 7. The copolymer of claim 1 wherein the boiling point of the organic solvent is 180 ° C. or higher. 8. water content of the organic solvent to be added charged to the reaction mixture is 50ppm or less claims 1 copolymer according. 9. The copolymer according to claim 1, which is obtained by first removing water from the reaction mixture by azeotropic distillation and then removing a part of the organic solvent from the reaction mixture.