JP3517856B2 - Polylactic acid production method - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing high molecular weight polylactic acid having excellent heat stability, and is useful as a biocompatible sustained-release polymer or biodegradable polymer.

[0002]

2. Description of the Related Art Polylactic acid has high biosafety, and lactic acid, which is a decomposition product, is absorbed in vivo. As described above, polylactic acid is a highly biosafe polymer compound, and is also used for medical purposes such as surgical sutures, drug delivery (sustained release capsules), and reinforcing materials for fractures, and decomposes in natural environments. Therefore, it is attracting attention as a degradable plastic. It is also used for various purposes such as uniaxially or biaxially stretched films, fibers, and injection molded products. In the production of such various molded products, mechanical properties equivalent to those of general-purpose resins are required, and for that purpose, high molecular weight polylactic acid that is less likely to be thermally decomposed during molding is required.

[0003] Such a method for producing polylactic acid includes a direct method for directly dehydrating and condensing lactic acid to obtain a desired product, and a method in which a cyclic lactide (dimer) is once synthesized from lactic acid and purified by a crystallization method or the like. Then, ring-opening polymerization is performed. Lactide synthesis, purification and polymerization procedures are described, for example, in US Pat.
57,537: Published European Patent Application No. 261,5
72: Polymer Bulletin, 14,491-495 (1985); and Makromol. Chem., 187, 1611-1628 (1986). In addition, Japanese Patent Publication Sho-56-146
In JP-A-88, two molecules of cyclic diester are used as intermediates,
It is disclosed that polylactic acid is produced by polymerizing this using tin octylate and lauryl alcohol as catalysts. Further, JP-A-7-33861 and JP-A-59-96123.
It can also be applied to the case where the polymerization is carried out directly from lactic acid as described in No. 1, Proc.

The polylactic acid thus obtained has a pellet shape such as a spherical shape, a cubic shape, a cylindrical shape, a crushed shape or the like, which has a size of rice grain to bean grain, in order to facilitate the handling in the molding process. Is a product of.

[0005]

In the polylactic acid polymerization step, when the reaction is carried out at a high temperature, for example, at 180 ° C.,
The polymer was depolymerized to generate lactide. Further, the melting point of high molecular weight polylactic acid having a molecular weight of 100,000 to 500,000 is 175.
The temperature is as high as ˜200 ° C., and when such a final polymer of polylactic acid was taken out from the reactor in a molten state and heated above the melting point, polylactic acid was decomposed or colored. Furthermore, at such temperatures, a large amount of lactide was generated in the polymer.

Regarding such a matter, Japanese Patent Laid-Open No. 3-14
No. 829 describes treating the reaction system under reduced pressure while keeping the polymer of glycolide / or lactide in a molten state. In order to process and use biodegradable plastics (particularly polylactic acid) like conventional plastics, it is necessary to perform various copolymerizations and blends to control the moldability and the physical properties of products. If the molecular component remains, it is gasified during the molding process and adheres to the spinning nozzle or die, deteriorating the operability. Further, the remaining low molecular weight component reduces the melt viscosity, and the gasified low molecular weight component worsens the working environment. Further, Chemical Engineering Magazine, Vol. 67, No. 2 (1964), p362-366 describes that polyglycolide is treated by a vacuum melting reaction to distill off low-molecular substances.

However, since there is an equilibrium between the polymer and lactide or lactic acid, it is not possible to sufficiently reduce these low-molecular components by the method (2) without deactivating the catalyst.

Therefore, the present invention is to produce a high molecular weight polylactic acid excellent in thermal stability, which is free from such coloring, decomposition products and lactide and has a form suitable for molding.

[0009]

Means for Solving the Problems The present inventor has diligently studied the above problems. As a result, in the polymerization process of polylactic acid, it is considered that the decomposition reaction can be suppressed by lowering the catalytic activity before the completion of the polymerization reaction. They have found that they have a function of suppressing the decomposition of lactic acid, and have completed the present invention. That is, the present invention is
In a method for producing polylactic acid having lactic acid as a main minimum constituent unit and copolymerizing and / or blending with other resin,
In the latter half of the polymerization when the weight average molecular weight became 50,000 or more in the polymerization reaction or after the completion of the polymerization , dipotassium hydrogen phosphate and diphosphate
Potassium hydrogen, potassium pyrophosphate, calcium pyrophosphate
Um, sodium dihydrogen phosphate, aluminum phosphate,
Aluminum dihydrogen phosphate and bis (3,5-di-t-
Butyl-4-hydroxybenzylphosphonate ethyl)
A method for producing polylactic acid, which comprises adding a phosphoric acid metal salt selected from lucium .

The polymerization temperature in the method for producing polylactic acid of the present invention is 1
20 to 250 ° C., preferably 140 to 180 ° C., 140 to 1 in order to suppress racemization and decomposition coloring of lactide.
Perform at 60 ° C. Polymerization gives polylactic acid having an average molecular weight of 50,000 to 300,000. The polymerization is carried out, for example, in one or more vertical reactors, to a state in which it can flow sufficiently easily. In a vertical reactor, the polymer viscosity increases as the polymerization progresses, so
Preference is given to working in a plurality of reactors with blades corresponding to different viscosities. In addition, even when performing continuous operation, the residence time distribution becomes sharp, and a plurality of reactors are connected in series to increase the heat transfer area per volume. For example, first using a reactor equipped with inclined blades, turbine blades, full-face blades,
Stir the catalyst uniformly in the low viscosity range. Next, the mixture is stirred with a reactor having a blade for high viscosity such as a helical ribbon blade. In addition,
When using multiple reactors, the reaction temperatures do not necessarily have to be the same.

The catalyst used for the polymerization is usually a catalyst comprising at least one metal or metal compound selected from the group consisting of groups IA, IVA, IVB and VA of the periodic table. Examples of the compounds belonging to Group IVA include organotin catalysts (tin lactate, tin dicaprylate tartrate, tin dilaurate, tin dipalmitate, tin distearate, tin dioleate, α-tin naphthate,
In addition to β-tin naphthate, tin octylate, etc.), powdered tin and the like can be mentioned.

Examples of the compounds belonging to Group IA include alkali metal hydroxides (sodium hydroxide, potassium hydroxide, lithium hydroxide, etc.), alkali metal and weak acid salts (sodium lactate, sodium acetate, sodium carbonate, etc.).
Sodium octylate, sodium stearate, potassium lactate, potassium acetate, potassium carbonate, potassium octylate, etc., alkali metal alkoxides (sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, etc.) and the like. it can.

Examples of compounds belonging to Group IVB include titanium compounds such as tetrapropyl titanate and zirconium compounds such as zirconium isopropoxide. Examples of compounds belonging to Group VA include antimony compounds such as antimony trioxide.

All of these are conventionally known polylactic acid polymerization catalysts, and among them, catalysts made of tin or tin compounds are particularly preferable from the viewpoint of activity. Also,
The molecular weight of the final polymer can also be adjusted by the amount of catalyst added. The lower the amount of catalyst, the slower the reaction rate, but the higher the molecular weight. A nucleating agent (talc, clay, titanium oxide, etc.) may be added.

The lactide used in the case of the lactide method is selected from D-, L-, DL- or a mixture of D-, L-, etc., and lactones such as β-propiolactone,
Copolymerization with δ-barrel lactone, ε-caprolactone, glycolide, δ-butyl lactone, dicarboxylic acid, diol, hydroxycarboxylic acid, polyhydric alcohol, and aliphatic polyester is also possible.

The polymerization reaction varies depending on the type of catalyst, but when tin octylate is used, it is 0.
0001-5% by weight, preferably 0.005-0.05
Polymerization is usually carried out by heating for 1.0 to 30 hours using a catalyst of wt%. The reaction is preferably carried out in an atmosphere of an inert gas such as nitrogen or in an air stream.

A phosphoric acid metal salt is added in the latter half of the polymerization or after the completion of the polymerization. The latter half of the polymerization means, for example, when the weight average molecular weight is 50,000 or more in the polymerization reaction. The amount added is in the range of 0.5 to 20 times the amount of the catalyst used for polymerization. 0.5
If it is less than 20, the activity of the catalyst cannot be suppressed, and if it exceeds 20, the phosphoric acid-based metal salt adversely acts on the heat stability-inhibiting load, and the polymer becomes cloudy or colored to impair the quality.

As the metal salt of phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, potassium pyrophosphate ,
Calcium pin pyrophosphate, Ri do disodium hydrogen, aluminum phosphate, aluminum dihydrogen phosphate and bis (3,5-di -t- butyl-4-hydroxybenzyl phosphonic acid ethyl) use those selected from calcium Ira
Re that.

At the end of the polymerization reaction, a phosphoric acid-based metal salt is added, and then depressurization is carried out in the molten state of the polymer, and after the completion of the polymerization reaction, unreacted lactide and low-molecular-weight substances such as lactic acid are removed from the pellet molded product. However, polylactic acid having a high molecular weight and a low monomer content and excellent in thermal stability can be obtained. Further, known additives such as stabilizers (calcium stearate, etc.), plasticizers (phthalic acid esters, etc.), colorants (red lead yellow lead, titanium oxide, etc.) may be added to the polylactic acid.

[0020]

EXAMPLES The method of the present invention was confirmed by the following experiments. [Example 1] L-lactide (500 g) was placed in a 1000 ml flask equipped with a stirrer and a thermometer, the lactide was melted at a temperature of 160 ° C while stirring under a nitrogen atmosphere, and then 0.05 g of tin octylate was added. After 1 hour, screws (3,
Ethyl 5-di-t-butyl-4-hydroxybenzylphosphonate) calcium and polyethylene wax 1:
0.4 g (8. 1) of a mixture (trade name: IRGANOX 1425WL).
(0 times the amount) and after stirring for 15 minutes, the contents of the flask are charged into a horizontal twin-screw kneader, and the temperature is 180 ° C. and the degree of vacuum is 10
Unreacted lactide was removed with mmHg, and after 10 minutes, pelletized polylactic acid was recovered. As a result of measuring the molecular weight of the recovered polylactic acid, the molecular weight was 165,000. About 1 g of this polylactic acid was placed in a 10 ml test tube with a stopper, sealed with nitrogen, left at 190 ° C. for 30 minutes, and subjected to a thermal decomposition test. The results are shown in Table 1.

[Example 2] 10 equipped with a stirrer and a thermometer
L-lactide (500 g) was placed in a 00 ml flask, the lactide was melted at a temperature of 160 ° C. with stirring under a nitrogen atmosphere, 0.05 g of tin octylate was added, and 1 hour later, 0.1 g of potassium pyrophosphate ( (2.0 times the amount) and after stirring for 15 minutes, the content of the flask was put into a horizontal twin-screw kneader to remove unreacted lactide at a temperature of 180 ° C. and a reduced pressure of 10 mmHg, and after 10 minutes, pelletized poly Lactic acid was recovered. As a result of measuring the molecular weight of the recovered polylactic acid, the molecular weight was 160000. About 1 of this polylactic acid
g in a 10 ml test tube with a stopper, nitrogen-filled, and 190
Table 1 shows the results of a thermal decomposition test that was carried out by leaving it at 30 ° C. for 30 minutes.

[Example 3] 10 equipped with a stirrer and a thermometer
L-lactide (500 g) was placed in a 00 ml flask, the lactide was melted at a temperature of 160 ° C. under stirring under a nitrogen atmosphere, 0.05 g of tin octylate was added, and 1 hour later, 0.5 g of sodium dihydrogen phosphate was added. (10.0 times the amount)
After adding and stirring for 15 minutes, the contents of the flask were put into a horizontal twin-screw kneader, the temperature was 180 ° C., the degree of vacuum was 10 mmHg.
The unreacted lactide was removed in 10 minutes, and after 10 minutes, pelletized polylactic acid was recovered. As a result of measuring the molecular weight of the recovered polylactic acid, the molecular weight was 170000. Approximately 1 g of this polylactic acid was placed in a 10 ml test tube with a stopper, and nitrogen was sealed.
Table 1 shows the results of the thermal decomposition test after leaving it at 0 ° C for 30 minutes.
Shown in.

[Example 4] 10 equipped with a stirrer and a thermometer
L-lactide (500 g) was placed in a 00 ml flask, the lactide was melted at a temperature of 160 ° C. under stirring under a nitrogen atmosphere, 0.05 g of tin octylate was added, and 1 hour later, 0.025 g of sodium dihydrogen phosphate was added. (0.5 times the amount) and after stirring for 15 minutes, the contents of the flask were put into a horizontal twin-screw kneader, the temperature was 180 ° C, and the degree of vacuum was 10 mm
Unreacted lactide was removed with Hg, and after 10 minutes, pelletized polylactic acid was recovered. As a result of measuring the molecular weight of the recovered polylactic acid, the molecular weight was 155,000. Approximately 1 g of this polylactic acid was placed in a 10 ml test tube with a stopper, and nitrogen was sealed,
Table 1 shows the results of a thermal decomposition test that was carried out at 190 ° C. for 30 minutes.

[Example 5] 10 equipped with a stirrer and a thermometer
L-lactide (500 g) was placed in a 00 ml flask, the lactide was melted at a temperature of 160 ° C. under stirring in a nitrogen atmosphere, 0.05 g of tin octylate was added, and 1 hour later, 1.0 g of sodium dihydrogen phosphate was added. (20.0 times the amount)
After adding and stirring for 15 minutes, the contents of the flask were put into a horizontal twin-screw kneader, the temperature was 180 ° C., the degree of vacuum was 10 mmHg.
The unreacted lactide was removed in 10 minutes, and after 10 minutes, pelletized polylactic acid was recovered. As a result of measuring the molecular weight of the recovered polylactic acid, the molecular weight was 155,000. Approximately 1 g of this polylactic acid was placed in a 10 ml test tube with a stopper, and nitrogen was sealed.
Table 1 shows the results of the thermal decomposition test after leaving it at 0 ° C for 30 minutes.
Shown in.

[Example 6] 10 equipped with a stirrer and a thermometer
L-lactide (500 g) was placed in a 00 ml flask, the lactide was melted at a temperature of 160 ° C. under stirring in a nitrogen atmosphere, 0.05 g of tin octylate was added, and 1 hour later, 0.01 g of potassium pyrophosphate ( (0.2 times the amount) and after stirring for 15 minutes, the contents of the flask were put into a horizontal twin-screw kneader to remove unreacted lactide at a temperature of 180 ° C. and a degree of vacuum of 10 mmHg, and after 10 minutes, pelletized poly Lactic acid was recovered. As a result of measuring the molecular weight of the recovered polylactic acid, the molecular weight was 140,000. About 1 of this polylactic acid
g in a 10 ml test tube with a stopper, nitrogen-filled, and 190
Table 1 shows the results of a thermal decomposition test that was carried out by leaving it at 30 ° C. for 30 minutes.

[Embodiment 7] 10 equipped with a stirrer and a thermometer
L-lactide (500 g) was placed in a 00 ml volumetric flask, the lactide was melted at a temperature of 160 ° C. under stirring in a nitrogen atmosphere, 0.05 g of tin octylate was added, and 1 hour later, 1.2 g of potassium pyrophosphate ( (24.0 times amount) and stirred for 15 minutes, and then the content of the flask was put into a horizontal twin-screw kneader to remove unreacted lactide at a temperature of 180 ° C. and a reduced pressure of 10 mmHg, and after 10 minutes, pelletized poly Lactic acid was recovered. As a result of measuring the molecular weight of the recovered polylactic acid, the molecular weight was 150,000. About 1 of this polylactic acid
g in a 10 ml test tube with a stopper, nitrogen-filled, and 190
Table 1 shows the results of a thermal decomposition test that was carried out by leaving it at 30 ° C. for 30 minutes.

[Comparative Example] For comparison, the same reaction was carried out as in the above Examples without adding the phosphoric acid metal salt, and as a result, the polylactic acid obtained had a molecular weight of 145,000. Table 1 shows the results of the thermal decomposition test similar to the above for this polylactic acid.

[0028]

[Table 1] It can be seen from Table 1 that when the phosphoric acid metal salt is not added, the rate of decrease in molecular weight is large and the composition is thermally unstable. The analysis conditions of the examples are as follows. <GPC measurement> Shimadzu Corporation detector; RID-6A pump; LC-9A column oven; CTO-6A column; Shim-pack GPC-801C, -804C, -806C, -8025C in series Analysis conditions Solvent; Chloroform Flow rate: 1 ml / min Sample volume: 200 μl (0.5 w / w% of sample was dissolved in chloroform) Column temperature: 40 ° C

[0029]

According to the production method of the present invention, it is possible to produce high-molecular-weight polylactic acid having a molecular weight of 50,000 to 500,000, which is less likely to be depolymerized by heat.

Claims (4)

(57) [Claims] 1. A method for producing polylactic acid, which comprises lactic acid as a main constituent unit and is copolymerized and / or blended with another resin , wherein the weight average molecular weight is 50,000 or more in the polymerization reaction.
In the latter half of the polymerization or after the completion of polymerization , dibasic hydrogen phosphate
Um, potassium dihydrogen phosphate, potassium pyrophosphate,
Calcium rophosphate, sodium dihydrogen phosphate, phosphoric acid
Aluminum, aluminum dihydrogen phosphate and bis
(3,5-di-t-butyl-4-hydroxybenzylpho
A process for producing polylactic acid, which comprises adding a phosphoric acid-based metal salt selected from calcium ethyl sulfonate . 2. The phosphoric acid metal salt is sodium dihydrogen phosphate, potassium pyrophosphate or bis (3,5-di-t-).
2. A process for producing polylactic acid according to claim 1, which is calcium butyl-4-hydroxybenzylphosphonate. 3. A method for producing polylactic acid according to claim 1 or 2 wherein 0.5 to 20 times by weight relative to the amount of catalyst used in the addition amount of phosphoric acid metal salt is polymerized. 4. The weight average molecular weight of the polymerization reaction is 50,000 or more.
Since polymerization late or completion of the polymerization after phosphoric acid metal salt is added, by vacuum and / or inert gas stream in the molten state and / or solid state, either 請 Motomeko 1-3 remove low molecular components Or a method for producing polylactic acid as described above.