JP3184680B2 - Purification method of polyhydroxycarboxylic acid - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for purifying a polyhydroxycarboxylic acid useful as a biodegradable polymer as a substitute for a medical material or a general-purpose resin.

[0002]

2. Description of the Related Art Polyhydroxycarboxylic acids not only have excellent mechanical properties and physical and chemical performances, but are also decomposed in a natural environment without harm to others. It has a biodegradable function of becoming carbon dioxide. For this reason, it is a plastic that has recently been used as a substitute for medical materials and general-purpose resins, and has attracted attention in various fields. In particular, at a time when environmental issues are being highlighted, it can be said that such plastics meet the needs of the times.

[0003] Usually, as a method for producing polyhydroxycarboxylic acid, when a hydroxycarboxylic acid such as lactic acid or glycolic acid is used as a raw material, dehydration dimerization is performed to obtain a cyclic dimer, and then a catalyst (Sn Ring-opening melt polymerization in the presence of a system catalyst) is known. But with this method,
The operation of the reaction is complicated, and the obtained polymer is expensive. Furthermore, since the production method is a method of obtaining a product as pellets as it is after melt polymerization, there is a disadvantage that the catalyst used at the time of polymerization remains in the polymer as it is. In particular, the incorporation of a catalyst into a product may have a serious adverse effect depending on the purpose of use. For example, in the case of application to an organism such as a sustained-release preparation, the polymer is decomposed, but the catalyst remains in the biological tissue as it is,
Cannot be used if catalyst is toxic. Further, the degradability of the polymer varies depending on the remaining amount of the catalyst, and the sustained release function cannot be sufficiently exhibited. in this way,
The use of the polymer is greatly restricted by impurities such as a catalyst contained therein.

[0004] On the other hand, several methods for obtaining the polymer without using a catalyst of the type described above have been disclosed. For example, a method of obtaining a copolymer from glycolide and lactide using a strongly acidic ion exchanger (European Patent No. 26599, JP-A-56-45920), a homopolymer or copolymer of lactic acid and glycolic acid by dehydration polycondensation (EP 171907,
Japanese Patent Application Laid-Open No. 61-28521 discloses a method of polymerizing in the presence of an inorganic solid acid catalyst). However, the weight average molecular weight of the obtained polymer is as low as 5,000 to 30,000, and the mechanical properties and chemical / physical properties are low. Performance is insufficient,
Its use is severely restricted. As described above, in the production of polyhydroxycarboxylic acid having a sufficient molecular weight, at present, it is unavoidable that a catalyst is mixed without purification.

[0005] On the other hand, several methods have been disclosed as to a purification method for removing a catalyst in the polymer. For example, once a polymer containing a catalyst is dissolved in a water-immiscible organic solvent, and then contacted with an aqueous layer or water containing an inorganic acid, a water-soluble organic acid or a water-soluble complexing agent, and the polymer is separated after separating the organic layer. By a known method (JP-A-63-14)
No. 5327), and a method of purifying the polymer by dissolving the polymer in a good solvent and adding a precipitant in a turbulent shearing field (JP-A-63-254128). Although these methods can certainly remove the catalyst in the polymer, they have the following problems industrially.

[0006] In JP-A-63-145327,
First, because the polymer solution dissolved in the organic solvent is viscous,
Under normal stirring, the contact efficiency with an aqueous layer such as an inorganic acid is poor,
As a result, the catalyst removal efficiency is not very good. Second, the liquid separation after mixing the organic solvent solution of the polymer with the aqueous layer is extremely poor. For this reason, there are restrictions such as lowering the polymer concentration in order to improve the liquid separation property (volume efficiency is remarkably deteriorated). Third, there are problems such as difficulty in precipitating and isolating the polymer. Japanese Patent Application Laid-Open No. 63-254128 discloses a method in which purification is performed at the same time as precipitation. Although this method is simpler than the former method, it has problems such as requiring special equipment.

As described above, in any of the methods, a process of once dissolving in a good solvent and then adding a poor solvent again to precipitate and isolate the polymer is required to remove the catalyst in the polymer. There has been no purification method that has always been satisfactory to date, for example, the types of solvents used for the purification have increased, and a great deal of labor, equipment and cost have been required.

[0008]

SUMMARY OF THE INVENTION It is a first object of the present invention to provide a method for removing a catalyst without dissolving a polyhydroxycarboxylic acid obtained by a polymerization reaction. The object of the invention is to provide polyhydroxycarboxylic acids having a very low catalyst content.

The present inventors have conducted intensive studies on a method for industrially and inexpensively removing the catalyst in the polymer. As a result, the present inventors have found that a solid polyhydroxycarboxylic acid having a specific intrinsic viscosity can be obtained in the presence of an organic solvent. It has been found that the catalyst in the polymer can be removed only by contact with an acidic substance, and the present invention has been completed.

That is, the present invention has a logarithmic viscosity of 0.1 to
The present invention relates to a method for purifying a polyhydroxycarboxylic acid, which comprises contacting a solid substance of 5.0 dl / g of a polyhydroxycarboxylic acid with an acidic substance in the presence of the solvent without dissolving the same in an organic solvent. is there.

According to the method of the present invention, the catalyst in the solid polyhydroxycarboxylic acid obtained by the polymerization reaction can be efficiently removed by a simple and economically advantageous method. Further, the present invention has made it possible to provide a polyhydroxycarboxylic acid having excellent heat resistance and weather resistance.

The polyhydroxycarboxylic acid used in the present invention is a polymer derived from an aliphatic hydroxycarboxylic acid, specifically, 2-hydroxyethanolic acid (glycolic acid) and 2-hydroxypropanoic. Acid (lactic acid), 2-hydroxybutanoic acid, 2-hydroxypentanoic acid, 2
-Hydroxyhexanoic acid, 2-hydroxyheptanoic acid, 2-hydroxyoctanoic acid, 2-hydroxy-2-methylpropanoic acid, 2-hydroxy-2-methylbutanoic acid, 2-hydroxy -2-ethylbutanoic acid, 2-hydroxy-2-methylpentanoic acid, 2-hydroxy-2-ethylpentanoic acid, 2-hydroxy-2-propylpentanoic acid, 2-hydroxy-2 -Butylpentanoic acid, 2-hydroxy-2-methylhexanoic acid, 2-hydroxy-2-ethylhexanoic acid, 2-hydroxy-2-propylhexanoic acid, 2-hydroxy-2-butyl Hexanoic acid, 2- Droxy-2-pentylhexanoic acid, 2-hydroxy-2-methylheptanoic acid, 2-hydroxy-2-ethylheptanoic acid, 2-hydroxy-2-propylheptanoic acid, 2-hydroxy-2 -Butylheptanoic acid, 2-hydroxy-2-pentylheptanoic acid, 2-hydroxy-2-hexylheptanoic acid, 2-hydroxy-2-methyloctanoic acid, 2-hydroxy-2-ethyl Octanoic acid, 2-hydroxy-2-propyloctanoic acid, 2-hydroxy-2-butyloctanoic acid, 2-hydroxy-2-pentyloctanoic acid, 2-hydroxy-2-hexyloctano Ic Acid, 2-Hide Carboxymethyl-2-heptyl-octanoic acid, 3-hydroxy propanoate dichroic acid, 3-hydroxy butanoate dichroic acid,
3-hydroxypentanoic acid, 3-hydroxyhexanoic acid, 3-hydroxyheptanoic acid, 3-hydroxyoctanoic acid, 3-hydroxy-3-methylbutanoic acid, 3-hydroxy-3- Methylpentanoic acid, 3-hydroxy-3-ethylpentanoic acid, 3-hydroxy-3-methylhexanoic acid, 3-hydroxy-3-ethylhexanoic acid, 3-hydroxy-3-propylhexa Neuic acid, 3-hydroxy-3-methylheptanoic acid, 3-hydroxy-3-ethylheptanoic acid, 3-hydroxy-3-propylheptanoic acid, 3-hydroxy-3-butylheptanoic Acid, 3-hydroxy -3-methyloctanoic acid, 3-hydroxy-3-ethyloctanoic acid, 3-hydroxy-3-propyloctanoic acid, 3-hydroxy-3-butyloctanoic acid, 3-hydroxy-3 -Pentyl octanoic acid, 4-hydroxybutanoic acid, 4
-Hydroxypentanoic acid, 4-hydroxyhexanoic acid, 4-hydroxyheptanoic acid, 4-hydroxyoctanoic acid,
4-hydroxy-4-methylpentanoic acid,
4-hydroxy-4-methylhexanoic acid,
4-hydroxy-4-ethylhexanoic acid,
4-hydroxy-4-methylheptanoic acid,
4-hydroxy-4-ethylheptanoic acid,
4-hydroxy-4-propylheptanoic acid, 4-hydroxy-4-methyloctanoic acid, 4-hydroxy-4-ethyloctanoic acid, 4-hydroxy-4-propyloctanoic acid, 4- Hydroxy-4-butyl octanoic acid, 5-hydroxypentanoic acid, 5-hydroxyhexanoic acid, 5-hydroxyheptanoic acid, 5-hydroxyoctanoic acid, 5-hydroxy-5-methylhexa Neuic acid, 5-hydroxy-5-methylheptanoic acid, 5-hydroxy-5-ethylheptanoic acid, 5-hydroxy-5-methyloctanoic acid, 5-hydroxy-5-ethyloctanoic Acid, 5-hydro Shi-5-propyl-octanoic acid, 6-hydroxy hexanoic acid, 6
-Hydroxyheptanoic acid, 6-hydroxyoctanoic acid, 6-hydroxy-6-methylheptanoic acid, 6-hydroxy-6-methyloctanoic acid, 6-hydroxy-6-ethyloctanoic acid 7-hydroxyheptanoic acid, 7-hydroxyoctanoic acid,
7-hydroxy-7-methyloctanoic acid,
Homopolymers and copolymers of polyhydroxycarboxylic acids derived from 8-hydroxyoctanoic acid and the like.

The above-mentioned hydroxycarboxylic acids have optically active carbon and may take the form of D-form, L-form and D / L-form, respectively. Has no restrictions. In addition, these polymers may be a mixture, and the polymer composition is not limited at all.

The polymer used in the present invention has a logarithmic viscosity in the range of 0.1 to 5.0 dl / g. 0.1d
When the amount is less than 1 / g, it is difficult to obtain a solid polymer by a usual method, so that the method of the present invention may not be applied in some cases. It is known that the polymer is usually obtained by a melt polymerization method via a cyclic dimer represented by JP-B-56-014688 or a direct dehydration polymerization method of hydroxycarboxylic acid represented by JP-A-61-28521. Have been.

The direct dehydration polymerization method in the present invention refers to a method in which hydroxycarboxylic acid or its oligomer is
It refers to a polymerization method in which a polymer is directly obtained from raw materials while dehydrating water generated from the reaction system using a metal such as n, Ti, Ni or the like as a catalyst. By using this method, it is possible to obtain a polyhydroxycarboxylic acid homopolymer or copolymer having a logarithmic viscosity of 0.3 dl / g or more. The amount of the residual catalyst referred to in the present invention is indicated by the metal content in the polymer. The polymer applied to the method of the present invention may be produced by any method, and the production method is not limited at all.

Examples of the acidic substance used in the present invention include inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid, and organic acids such as acetic acid and p-toluenesulfonic acid. Nitric acid and the like are preferred. The acidic substance may be in a gaseous state.

The amount of the acidic substance to be used is preferably 0.0001 to 5.0 mol / 100 parts by weight, particularly preferably 0.001 to 1 mol / 100 parts by weight, based on the polymer. If the amount is less than 0.0001 mol, the effect of removing the catalyst tends to decrease. If the amount is more than 5.0 mol, problems such as deterioration of the polymer may occur. Further, the use of an excessive amount of an acidic substance does not have any effect on the removal of the catalyst, and further requires excessive purification for removing the acidic substance.

The organic solvent used in the present invention is not particularly limited, and aromatic hydrocarbons and the like can be used, but hydrophilic solvents such as alcohols, ketones, ethers, carboxylic acids, nitriles, and amides are used. Is preferred.

As alcohols, methanol, ethanol, propanol, isopropanol, butanol,
sec-butanol, tert-butanol, pentanol, etc .; ketones such as acetone and methyl ethyl ketone; ethers such as tetrahydrofuran; carboxylic acids such as acetic acid and butyric acid; nitriles such as acetonitrile; N-dimethylformamide, N, N-dimethylacetamide, 1,3-
Examples thereof include dimethylimidazolidinone and hexamethylphosphoramide, and preferred are alcohols which are inexpensive and do not dissolve the polymer. In the present invention, these organic solvents may be one or more mixtures.

The process of the present invention is a process for removing the catalyst in the polymer by bringing the solid polyhydroxycarboxylic acid into contact with the acidic substance in the presence of an organic solvent. The solid polyhydroxycarboxylic acid may be in any form of powder, granule, granule, flake, and block. In general, as a method for obtaining a polymer of these forms, a method of once dissolving a polymer in a good solvent and then dropping a poor solvent or in a poor solvent, or a method described in Japanese Patent Application Laid-Open Nos. There is known a method such as a method of obtaining the polymer by dissolving in a specific solvent by heating and then cooling and crystallizing the polymer as disclosed in Japanese Patent No. 42531. It may be obtained by the method. As the properties of the polymer, the bulk density is preferably 0.60 g / ml or less. If the bulk density is larger than 0.6 g / ml, the catalyst in the polymer may not be completely removed due to insufficient contact with the acidic substance. Although there is no problem in the removal, there may be a problem in operation due to poor filterability after the treatment.

With respect to the conditions under which the acidic substance is brought into contact with the solid polyhydroxycarboxylic acid, the solid concentration of the polymer is usually 3 to 40% by weight, but the concentration is not limited at all. The contacting temperature is usually 0 to 100 ° C., preferably 0 to 6 ° C., depending on the stability of the polymer.
0 ° C is good. If the temperature is lower than 0 ° C., an extra cooling capacity is required, which is costly and industrially disadvantageous.
Higher values tend to result in polymer degradation.

The pressure at the time of contact may be any of normal pressure, reduced pressure, and increased pressure, and is not limited. The contact method may be any of a sludge method, a stationary method, a column method and the like, and there is no limitation as long as the acidic substance is brought into contact with the polyhydroxycarboxylic acid.

The contact time may be 0.1 to 24 hours, preferably 0.5 to 8.0 hours. If the time is less than 0.1 hour, the removal of the catalyst may be insufficient, and if the time exceeds 24 hours, some compounds may deteriorate.

The treatment may be performed in any of a batch system, a semi-batch system and a continuous system. The physical properties are greatly affected by the amount of residual catalyst in the polymer after the treatment, and the amount is usually 200 ppm or less, preferably 100 ppm or less, more preferably 50 ppm or less.

The polyhydroxycarboxylic acid obtained by the purification method of the present invention substantially eliminates the adverse effects caused by the remaining catalyst as described above, and is used as a film or a plastic having excellent mechanical properties, heat resistance and light resistance. can do.

[0026]

EXAMPLES Examples of the present invention will be described below.
The present invention is not limited to this. In the synthesis examples and examples, the logarithmic viscosity (ηinh) is represented by the following formula, and is measured under the following conditions.

[0027]

(Equation 1)

Where t ₀ = flowing time of the solvent in the viscometer t = flowing time of the polymer-dilute solvent of the same solvent in the same viscometer C = concentration expressed in grams of polymer solids in 100 ml of the solvent , 0.1 g of polymer solid content / 20 ml of dichloromethane, and measured at a temperature of 20 ° C.

Synthesis Example 1 (Melting Polymerization Method) 1500 g of 90% L-lactic acid was charged into a 2000 ml three-necked flask equipped with a cooler, a thermometer, and a stirrer.
The degree of reduced pressure was gradually increased from normal pressure to 30 mmHg at ℃, and a dehydration reaction was performed for 8 hours. Add zinc powder to this and add 200 ℃
A cyclic dimer of lactic acid (lactide) distilled at / 5 mmHg / 4Hr was collected. The yield at this time is 8
It was 5 mol%. The lactide was recrystallized in ethyl acetate and dried, and then 0.1% by weight of tin octoate as a catalyst and 2% by weight of lauryl alcohol / lactic acid as a molecular weight regulator were added to the obtained lactide, and the mixture was heated at 180 ° C under a nitrogen atmosphere. /
The mixture was stirred at 4 hours. After completion of the reaction, the strand was taken out from the outlet at the bottom of the reactor, and the obtained strand was quickly cooled and cut with a pelletizer. The resulting polylactic acid had a logarithmic viscosity of 1.50 dl / g. 20 parts of the obtained polylactic acid and 100 parts of xylene were added to 200 ml of 3
The mixture was charged in a one-necked flask, heated and stirred at 140 ° C. for 2 hours to dissolve the polylactic acid, and then cooled at room temperature. The resulting slurry was filtered to obtain a polylactic acid cake, which was dried under a nitrogen atmosphere. The resulting powder has a bulk density of 0.20 g / m
l.

Synthesis Example 2 (Direct dehydration polymerization method) 36.0 g of 90% L-lactic acid was heated and stirred at 150 ° C./50 mmHg for 3 hours while distilling water out of the system to obtain 25.3 g of an oligomer. To this, add 0.088 g of tin powder,
The mixture was further stirred at 150 ° C./30 mmHg for 2 hours. D
ean Stark trap, tin tin 0.4
17 g and 75.9 g of diphenyl ether were added, and 130
An azeotropic dehydration reaction was carried out at a temperature of 12 ° C / mm for 1 hour to remove water. After that, the Dean Stark trap was removed, a tube filled with molecular sieve 3A, 20 g was attached, and the solvent distilled by reflux passed through the molecular sieve. I returned to the system again. 130 ° C / 12
The reaction was performed at mmHg for 48 hours. After completion of the reaction, the mixture was filtered and cooled to 50 ° C. to precipitate a polymer. This was filtered and the solvent was separated and removed.
1.5 g (83% yield) were obtained. The logarithmic viscosity of the obtained lactic acid was 1.50 dl / g.

Example 1 To 20 g of a polymer powder (logarithmic viscosity: 1.50 dl / g, Sn content: 560 ppm, bulk density: 0.2 g / ml) obtained from lactic acid shown in Synthesis Example 2, 40 ml of 0.5N hydrochloric acid and ethanol After adding 40 ml and stirring at 35 ° C. for 1 hour,
It was filtered and dried. The resulting powder has a bulk density of 0.20 g / ml
Met. The results are shown in Table 1.

Examples 2 to 11 Polymer raw materials, treatment solutions and contact conditions were changed as shown in Table 1. The results are shown in Table 1.

Comparative Example 1 The procedure was carried out by changing the polymer raw material, the treatment liquid and the contact conditions as shown in Table 1. The results are shown in Table 1.

[0034]

[Table 1]

[0035]

[Table 2]

Example 12 and Comparative Example 2 Using the L-polylactic acid obtained in Example 1 and Comparative Example 1, the following heat resistance test and weather resistance test were performed, respectively. The results are shown in Table 2. Heat resistance test 5%-Weight loss temperature Using TG / DTA220 manufactured by Seiko Denshi Kogyo Co., Ltd., 5%-
The temperature at the time of weight loss was measured. Molecular Weight Change The molecular weight change (logarithmic viscosity) when kept at 180 ° C. for 5 minutes was measured. Weather resistance test From polyhydroxycarboxylic acid powder, 180 ° C / 10
Under the condition of 0 kg / cm ² , press film (thickness 100
μm). The obtained film is transferred to Suga Standard Sunshine Weather Meter (WE-SUN)
Using a carbon arc light source, the temperature was maintained at 400 ° C. for 120 minutes (18 minutes shower) at 60 ° C. A tensile strength test was performed on the film before and after the test, and the strength retention was calculated.

[0037]

[Table 3]

[0038]

According to the present invention, the catalyst contained in the polyhydroxycarboxylic acid can be efficiently removed by a simple method, and the mechanical properties, heat resistance, and weather resistance are substantially free from adverse effects due to the remaining catalyst. Excellent polyhydroxycarboxylic acid can be provided.

Claims (4)

(57) [Claims] 1. A solid polyhydroxycarboxylic acid having a logarithmic viscosity of 0.1 to 5.0 dl / g is contacted with an acidic substance in the presence of an organic solvent without being dissolved in the organic solvent. A method for purifying a polyhydroxycarboxylic acid. 2. The method according to claim 1, wherein the bulk density of the polyhydroxycarboxylic acid is 0.05 to 0.6 g / ml. 3. The method according to claim 1, wherein the acidic substance is an inorganic acid or an organic acid. 4. The method according to claim 1, wherein the contact temperature is from 0 to 60 ° C.