JPH10158370A - Production of polylactic acid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce a polylactic acid of high molecular weight without coloration and formation of decomposition products by adding an antioxidant at an early stage of lactic acid polymerization process. SOLUTION: This polylactic acid is obtained by carrying out a polymerization of (A) lactic acid or a lactide as a starting material by adding, to the reaction system, (B) an antioxidant (preferably phenol- or phosphite-based antioxidants or a mixture of them, for example, 1,1, θ 3-tris(2-methyl-4-di-tridecylphosphite-5-t- butylphenyl) butane in weight of 1-10 times the quantity of the catalyst used for the polymerization, and preferably at a temperature of 140-250 deg.C in the condition that the timing to add the component B is at least once among periods from start of the polymerization to the time points at which the polymer ratio reaches 90%, 60% and 30%.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a high molecular weight polylactic acid, and an object of the present invention is to provide a high molecular weight polylactic acid useful as a biocompatible sustained-release polymer and a biodegradable polymer.

[0002]

2. Description of the Related Art Polylactic acid has high biological safety, and lactic acid, which is a decomposition product, is absorbed in vivo. As described above, polylactic acid is a high biosafety polymer compound, and is used for medical purposes such as surgical sutures, drug delivery (sustained release capsules), and reinforcing materials for bone fractures, and decomposes in the natural environment. For this reason, it is attracting attention as a degradable plastic. It is also used for various applications as uniaxially and biaxially stretched films, fibers, injection molded products and the like. In the production of such various molded products, low colorability is required in addition to the mechanical properties equivalent to general-purpose resins. In particular, colorless and transparent products are required for film / sheet molding. For this purpose, high-molecular-weight polylactic acid with little coloring during molding is required.

[0003] Such a method for producing polylactic acid includes a direct method in which lactic acid is directly dehydrated and condensed to obtain a target product, and a method in which cyclic lactide (dimer) is once synthesized from lactic acid and purified by a crystallization method or the like. And then ring-opening polymerization. Lactide synthesis, purification and polymerization procedures are described, for example, in US Pat.
No. 57,537: Published European Patent Application No. 261,5
No. 72: Polymer Bulletin, 14, 491-495 (1985); and various descriptions in the chemical literature such as Makromol. Chem., 187, 1611-1628 (1986). In addition, Japanese Patent Publication No. 56-146
No. 88 discloses two molecules of cyclic diester as an intermediate,
It is disclosed that this is polymerized using tin octylate and lauryl alcohol as catalysts to produce polylactic acid. Further, JP-A-7-33861, JP-A-59-96123
As described in Vol. 44, Preprints of the Symposium on Polymers, Vol. 44, p3198-3199, the method can also be applied to the case where direct polymerization is performed from lactic acid.

[0004] The polylactic acid thus obtained is preliminarily formed into pellets such as spheres, cubes, cylinders, crushed shapes, etc., each having a size from a rice grain to a bean grain, in order to facilitate handling in the molding process. Products.

[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. The melting point of high molecular weight polylactic acid having a molecular weight of 100,000 to 500,000 is 175.
Conventionally, such a final polymer of polylactic acid was taken out of the reactor in a molten state and heated to a temperature higher than the melting point, which caused decomposition of the polylactic acid and coloring of deep yellow to brown. .

[0006] Therefore, an object of the present invention is to produce a high molecular weight polylactic acid free of such coloring and decomposition products.

[0007]

Means for Solving the Problems As a result of intensive studies on the above-mentioned problems, the present inventors have found that in the polymerization process of polylactic acid, coloring can be suppressed by adding an antioxidant at an early stage of the polymerization reaction. In particular, they have found that a phenolic antioxidant and a phosphite antioxidant have a function of suppressing the coloring of polylactic acid, and have completed the present invention. That is, the present invention relates to a polymerization reaction for producing polylactic acid using lactic acid or lactide as a starting material,
A method for producing polylactic acid, comprising adding an antioxidant to a reaction system.

Here, the polymerization reaction for producing polylactic acid using lactic acid or lactide as a starting material is not limited to a polymerization reaction for obtaining a homopolymer of lactic acid, but may be carried out in the presence of another resin and / or a low molecular compound. Alternatively, it also includes a polymerization reaction for obtaining a blend.

The polymerization temperature of the method for producing polylactic acid of the present invention is 1
40 to 250 ° C, preferably 160 to 210 ° C, 160 to 1 to suppress racemization of lactide and decomposition coloration
Perform at 90 ° C. Polylactic acid having an average molecular weight of 50,000 to 500,000 is obtained by polymerization. The polymerization is carried out, for example, in one or more vertical reactors to a state where it is sufficiently easily flowable. As the viscosity of the polymer increases in the vertical reactor as the polymerization progresses,
It is preferably carried out in a plurality of reactors with blades corresponding to different viscosities. Also, when performing a continuous operation, the residence time distribution becomes sharp, and a plurality of reactors are connected in series in order to increase the heat transfer area per volume. For example, first use a reactor equipped with inclined blades, turbine blades, full blades, etc.
Stir the catalyst uniformly in the low viscosity region. Next, the mixture is stirred in a reactor having blades for high viscosity such as helical ribbon blades. In addition,
When a plurality of reactors are used, the respective reaction temperatures need not necessarily be the same.

The catalyst used in 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 those belonging to the IVA group include organotin catalysts (tin lactate, tin tartrate tin dicaprylate, tin dilariulate, tin dipalmitate, tin distearate, tin dioleate, tin α-naphate,
tin-naphthoate, tin octylate, etc.) and tin powder.

Examples of those belonging to Group IA include hydroxides of alkali metals (such as sodium hydroxide, potassium hydroxide and lithium hydroxide), and salts of alkali metals and weak acids (sodium lactate, sodium acetate, sodium carbonate, and the like).
Examples include sodium octylate, sodium stearate, potassium lactate, potassium acetate, potassium carbonate, potassium octylate, and the like, and alkoxides of alkali metals (such as sodium methoxide, potassium methoxide, sodium ethoxide, and potassium ethoxide). it can.

The compounds belonging to Group IVB include, for example, titanium compounds such as tetrapropyl titanate and zirconium compounds such as zirconium isopropoxide. Examples of those belonging to the VA group include antimony compounds such as antimony trioxide.

All of these are conventionally known polylactic acid polymerization catalysts, and among them, a catalyst composed of tin or a tin compound is particularly preferred from the viewpoint of activity. Also,
The molecular weight of the final polymer can also be adjusted by the amount of catalyst added. The smaller the amount of catalyst, the slower the reaction rate but the higher the molecular weight. Further, a nucleating agent (such as talc, clay, or titanium oxide) may be added.

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

The polymerization reaction varies depending on the type of the catalyst.
0001 to 5% by weight, preferably 0.005 to 0.05
The polymerization is usually carried out by heating for 1.0 to 30 hours using a catalyst of weight%. The reaction is preferably performed in an atmosphere of an inert gas such as nitrogen or in a stream.

Further, in order to terminate the polymerization reaction and to improve the thermal stability of the polymer, it is necessary to suppress the catalytic activity after the reaction, and it is necessary to reduce the activity of the phosphorous acid, meryl phosphite, sodium dihydrogen phosphate. Addition of a phosphorus compound such as

In the polymerization reaction, the time of addition of the antioxidant is from the start of polymerization to the polymer ratio of 90%, preferably from the start of polymerization to the polymer ratio of 60%, more preferably from the start of polymerization to the polymer ratio of 30%. Is added. The addition amount is in the range of 1 to 10 times the weight of the catalyst used for the polymerization. That is, if it is less than 1, a sufficient coloring prevention effect cannot be obtained,
If it exceeds 10, it acts on polymerization inhibition. As antioxidants,
Phenolic octadecyl-3- (3,5-di-t-butyl-4-
Hydroxyphenyl) propionate, pentaerythrityl-tetrakis [3- (3.5-di-t-butyl-4-hydroxyphenyl) propionate], tris- (3.5-di-t-butyl-4-hydroxybenzyl) -isocyanurate, Phosphite 4,4'-butylidenebis (3-methyl-6-t-
Butyl-di-tridecyl phosphite), 1.1.3-tris (2-methyl-4-di-tridecyl phosphite-5-t-
Butylphenyl) butane, cyclic neopentanetetraylbis (2.4-di-t-butylphenylphosphite) and the like can be used.

Further, polylactic acid includes a stabilizer (such as calcium stearate), a plasticizer (such as phthalate),
Any known additives such as coloring agents (eg, red-mouthed graphite, titanium oxide, etc.) may be added.

[0019]

EXAMPLES The method of the present invention was confirmed by the following experiments. Example 1 500 g of L-lactide was placed in a 1000 ml flask equipped with a stirrer and a thermometer, and lactide was melted at a temperature of 180 ° C. while stirring under a nitrogen atmosphere, and then 0.05 g of tin octylate, 4, 4'-butylidenebis (3-methyl-6-t-butyl-di-tridecylphosphite)
(Trade name: ADK STAB 260) 0.3 g (6.0 times the amount) was added, and after stirring for 2 hours, the contents of the flask were charged into a horizontal twin-screw kneader, and the temperature was 190 ° C. and the degree of vacuum was 10 mm.
Unreacted lactide was removed with Hg, and after 10 minutes, pelleted polylactic acid was recovered. As a result of measuring the molecular weight of the recovered polylactic acid, the molecular weight was 225,000. Table 1 shows the hue results of the polylactic acid by the CIELab method.

Example 2 10 equipped with a stirrer and a thermometer
500 g of L-lactide was placed in a 00 ml flask, and lactide was melted at a temperature of 180 ° C. while stirring under a nitrogen atmosphere. Then, 0.05 g of tin octylate and 1.1.3-tris (2-methyl-4-di-tri) were melted. Decylphosphite-5-t-butylphenyl) butane (trade name: ADK STAB 522)
A) 0.4 g (8.0-fold amount) was added, and after stirring for 2 hours,
The contents of the flask were charged into a horizontal twin-screw kneader, and the temperature was 190
Unreacted lactide was removed at 10 ° C. and a reduced pressure of 10 mmHg.
After 0 minute, pellet-shaped polylactic acid was recovered. As a result of measuring the molecular weight of the recovered polylactic acid, the molecular weight was 230,000. Table 1 shows the hue results of the polylactic acid by the CIELab method.

Example 3 10 equipped with a stirrer and a thermometer
500 g of L-lactide was placed in a 00 ml flask, and lactide was melted at a temperature of 180 ° C. while stirring under a nitrogen atmosphere. Then, 0.05 g of tin octylate and tris- (3.5-di-
t-butyl-4-hydroxybenzyl) -isocyanurate (trade name: ADK STAB A0-20, IRGANOX311)
4) 0.2 g (4.0 times) was added and stirred for 2 hours.
The contents of the flask were charged into a horizontal twin-screw kneader, and the temperature was 190
Unreacted lactide was removed at 10 ° C. and a reduced pressure of 10 mmHg.
After 0 minute, pellet-shaped polylactic acid was recovered. As a result of measuring the molecular weight of the recovered polylactic acid, the molecular weight was 20,5000. Table 1 shows the hue results of the polylactic acid by the CIELab method.

Example 4 10 equipped with a stirrer and a thermometer
500 g of L-lactide was placed in a 00 ml flask, and lactide was melted at a temperature of 180 ° C. while stirring under a nitrogen atmosphere, and then 0.05 g of tin octylate and ADK STAB 2
60: 0.05 g (1.0-fold amount) was added, and after stirring for 2 hours, the contents of the flask were charged into a horizontal twin-screw kneader and the temperature was adjusted to 1
Unreacted lactide was removed at 90 ° C. and a degree of reduced pressure of 10 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 2200
00. Table 1 shows the hue results of the polylactic acid by the CIELab method.

Example 5 10 equipped with a stirrer and a thermometer
500 g of L-lactide was placed in a 00 ml flask, and lactide was melted at a temperature of 180 ° C. while stirring under a nitrogen atmosphere, and then 0.05 g of tin octylate and ADK STAB 2
60: 0.5 g (10.0 times the amount) was added, and after stirring for 2 hours, the contents of the flask were charged into a horizontal twin-screw kneader and the temperature was adjusted to 1
Unreacted lactide was removed at 90 ° C. and a degree of reduced pressure of 10 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 2100
00. Table 1 shows the hue results of the polylactic acid by the CIELab method.

Example 6 10 equipped with a stirrer and a thermometer
500 g of L-lactide was placed in a 00 ml flask, and lactide was melted at a temperature of 180 ° C. while stirring under a nitrogen atmosphere, and then 0.05 g of tin octylate and ADK STAB 2
60: 0.04 g (0.8-fold amount) was added, and after stirring for 2 hours, the contents of the flask were charged into a horizontal twin-screw kneader, and the temperature was adjusted to 1
Unreacted lactide was removed at 90 ° C. and a degree of reduced pressure of 10 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 2250.
00. Table 1 shows the hue results of the polylactic acid by the CIELab method.

Example 7 10 equipped with a stirrer and a thermometer
500 g of L-lactide was placed in a 00 ml flask, and lactide was melted at a temperature of 180 ° C. while stirring under a nitrogen atmosphere, and then 0.05 g of tin octylate and ADK STAB 2
60: 0.6 g (12.0 times the amount) was added, and after stirring for 2 hours, the contents of the flask were charged into a horizontal twin-screw kneader and the temperature was adjusted to 1
Unreacted lactide was removed at 90 ° C. and a degree of reduced pressure of 10 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 1600.
00. Table 1 shows the hue results of the polylactic acid by the CIELab method.

[Comparative Example] For the purpose of comparison, the same reaction was carried out in the above Examples without adding an antioxidant.
The molecular weight of the obtained polylactic acid was 230,000. Table 1 shows the hue results of the polylactic acid according to the CIELab method.

[0027]

[Table 1] From Table 1, it can be seen that coloring is performed when the antioxidant is not added or when the amount added is small. In addition, the analysis conditions of an Example are as follows. <GPC measurement> Detector manufactured by Shimadzu Corporation; 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% sample was dissolved in chloroform) Column temperature; 40 ° C. <CIELab measurement> Color difference meter TC-1500MC-88 manufactured by Tokyo Denshoku Co., Ltd.

[0028]

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 with little coloring under high temperature polymerization conditions.

Claims (6)

[Claims] 1. A method for producing polylactic acid, which comprises adding an antioxidant to a reaction system in a polymerization reaction for producing polylactic acid using lactic acid or lactide as a starting material. 2. The method for producing polylactic acid according to claim 1, wherein the antioxidant is a phenol type, a phosphite type or a mixture thereof. 3. An antioxidant comprising 1.1.3-tris (2-methyl-4
3. Di-tridecylphosphite-5-t-butylphenyl) butane and 4-4'-butylidenebis (3-methyl-6-t-butyl-di-tridecylphosphite). A method for producing polylactic acid. 4. The process for producing polylactic acid according to claim 1, wherein the amount of the antioxidant added is 1 to 10 times the amount of the catalyst used for the polymerization. 5. The method according to claim 1, wherein the antioxidant is added at least once from the start of polymerization to the polymer ratio of 90%, from the start of polymerization to the polymer ratio of 60%, and from the start of polymerization to the polymer ratio of 30%. A method for producing polylactic acid according to any one of claims 1 to 4. 6. The method for producing polylactic acid according to claim 1, wherein the polymerization temperature is 140 to 250 ° C.