JP2002138142A - Method of producing polyhydroxycarboxylic acid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method of producing a biodegradable polyhydroxycarboxylic acid using a polymerization catalyst for polymerizing a hydroxycarboxylic acid such as lactic acid which scarcely affects environment even when dumped in the natural surroundings without recollecting after use, and further even if remaining in the product, does not cause a reaction with a drug or a harmful reaction in the living body. SOLUTION: This method of producing a high molecular weight polylactic acid or a lactic acid-sugar copolymer comprises adding phosphoric acid aqueous solution as a polymerization catalyst to L-lactic acid or a mixture of L-lactic acid and corn starch, and heating with agitation under reduced pressure or in the presence of an organic solvent such as D-limonene.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a polyhydroxycarboxylic acid which is a homopolymer or a copolymer of a hydroxycarboxylic acid, in particular, a biodegradable resin.

[0002]

2. Description of the Related Art Conventionally, various resin moldings have been used as agricultural and horticultural materials (for example, polyvinyl chloride film) and fishery materials (for example, fishing nets made of polyethylene fiber). Is what is done.
Therefore, there is a need for a resin that is hydrolyzed with time or biodegraded by microorganisms in the soil without polluting the environment even when discarded. The present inventors have previously made polyhydroxycarboxylic acids that can be used for such agricultural and horticultural materials, fishing materials, etc., and that are decomposed into carbon dioxide and water by microorganisms in the soil even if disposed after use. A method for easy manufacture has been invented.

[0003]

By the way, polyhydroxycarboxylic acid represented by polylactic acid is a biodegradable resin for which great demand is expected in the future, but the polymerization catalyst used in the conventional production method is one. , 3-substitution-1,
It is an organic metal compound such as 1,3,3-tetraorganodistanoxane, and has a problem in that when it is disposed of in a natural environment without being collected after use, it has a significant effect on the environment.

[0004] Further, in the polymerization of hydroxycarboxylic acid using a conventionally known metal phosphate such as aluminum phosphate, iron phosphate, calcium phosphate or the like as a catalyst, a metal atom part is coordinated to hydroxycarboxylic acid. It proceeds by activating the reactive site of hydroxycarboxylic acid.

Therefore, when a polyhydroxycarboxylic acid synthesized using a metal phosphate as a catalyst is used for medical purposes, for example, as a coating material for a drug, if the metal ion remains in the resin, the drug and the metal ion form a complex. Can form and interfere with the efficacy of the drug. For this reason, it is not preferable to use a polyhydroxycarboxylic acid synthesized using a metal phosphate as a catalyst for medical purposes without purification.

[0006] Furthermore, the use of phosphoric esters in the polymerization of hydroxycarboxylic acids has also been reported.
However, the phosphoric acid ester is not used as a catalyst but as a heat stabilizer and a reaction terminator. Phosphoric acid esters as heat stabilizers are used to prevent a thermal decomposition reaction during molding of polyhydroxycarboxylic acid. On the other hand, a phosphate ester as a reaction terminator is used to prevent the polymerization reaction from proceeding further. Here, the phosphate ester forms a complex with a catalyst (such as an organometallic compound, a metal salt, or a metal oxide), and has an action of stopping the catalyst cycle.

Further, K.K. Hiltunen et al. Report that sulfuric acid is a suitable acid catalyst for use in synthesizing polyhydroxycarboxylic acids (Macrom).
olecules, Vol. 30, no. 3, pp. 3
73-379, 1997). However, sulfuric acid causes reactions such as nitration and sulfonation with organic compounds. When these reactions occur in a living body, the living body may be adversely affected. Therefore, in order to use polyhydroxycarboxylic acid synthesized using sulfuric acid as a catalyst in medical applications, sulfuric acid must be removed.

The present invention provides a catalyst for polymerization of a hydroxycarboxylic acid or a mixture of a hydroxycarboxylic acid and a saccharide or metal oxide, which has little effect on the environment even when it is disposed of in the natural environment without being recovered after use. It is an object of the present invention to provide a method for producing a polyhydroxycarboxylic acid using a polymerization catalyst which does not cause a reaction with a drug or a harmful reaction in a living body even if it remains in a product without causing the reaction. Things.

[0009]

Means for Solving the Problems As a result of intensive studies, the present inventors have found that the above object can be achieved by using a phosphoric acid derivative as a polymerization catalyst, and have completed the present invention.

That is, the method for producing a polyhydroxycarboxylic acid of the present invention comprises the steps of:
Or, in a mixture of a hydroxycarboxylic acid and a saccharide or a metal oxide, a phosphoric acid derivative is added as a polymerization catalyst, and the mixture is heated and stirred under reduced pressure, or is subjected to azeotropic dehydration polymerization in an organic solvent. Things.

[0011]

DESCRIPTION OF THE PREFERRED EMBODIMENTS In the present invention, a phosphoric acid derivative is used as a polymerization catalyst used for a polymerization reaction of a hydroxycarboxylic acid or a mixture thereof.

As the phosphoric acid derivative, any Bronsted acid (ie, a chemical species capable of releasing hydrogen ions) which is non-toxic can be used.
For example, phosphoric acid, pyrophosphoric acid, polyphosphoric acid, phosphorus acetate and the like can be mentioned. However, phosphoric acid is preferably used because it is easily available and inexpensive. In the polymerization reaction of the hydroxycarboxylic acid in the present invention, the hydrogen ions (H ⁺ ) released from the phosphoric acid derivative cause the dehydration between the hydroxycarboxylic acids and esterification proceeds, and a metal phosphate is used. The reaction mechanism is different from the prior art.

[0013] Further, since phosphoric acid is an inorganic oxide and has low toxicity, even if it is discarded in a natural environment without being recovered after use, it hardly affects the environment. Furthermore, phosphoric acid is a weaker acid than sulfuric acid and does not cause reactions such as nitration and sulfonation with organic compounds, so there is no possibility of adverse effects in vivo, and phosphoric acid is approved as a food additive. Therefore, even if it is left in the living body after use, the effect on the living body is extremely small.

When phosphorous acid was examined, phosphoric acid was stable in air, whereas phosphorous acid was unstable in air, so that the polymerization reaction had to be carried out in a nitrogen gas atmosphere. The weight average molecular weight (Mw) of the obtained polyhydroxycarboxylic acid is at most about 11,000.

Further, since the phosphoric acid derivative is a polymerization catalyst having high catalytic activity, by using at least one kind of polysaccharide or metal oxide as a copolymerization component other than hydroxycarboxylic acid such as lactic acid, a higher molecular weight polysaccharide can be obtained. A hydroxycarboxylic acid is obtained.

The substituent of the phosphoric acid derivative is preferably hydrogen or a hydroxyl group. An aliphatic carboxylic acid or an aromatic carboxylic acid may be directly bonded to the phosphorus atom. Some phosphorus atoms may form an oligomer via an oxygen atom like pyrophosphoric acid and polyphosphoric acid.

The addition amount of the phosphoric acid derivative is preferably 0.001 to 1 part by weight based on 100 parts by weight of the hydroxycarboxylic acid. If the amount is less than 0.001 part by weight, remarkable catalytic activity cannot be obtained. If the amount exceeds 1 part by weight, the weight average molecular weight of the obtained polyhydroxycarboxylic acid decreases.

The hydroxycarboxylic acid used in the present invention is preferably an aliphatic carboxylic acid having a hydroxyl group in the molecule. When it has an asymmetric carbon, it may be any of D-form, L-form and racemic-form. Two or more hydroxycarboxylic acids may be used in combination. Specific examples of such hydroxycarboxylic acids include lactic acid, glycolic acid, tartaric acid, citric acid,
Malic acid and the like can be mentioned, and these are preferably used alone or as a mixture.

The saccharide used as a copolymer component of the present invention is preferably a natural product, such as D-glucose or D-glucose.
Monosaccharides such as fructose, D-mannose and D-galactose; oligosaccharides (oligosaccharides) such as maltose and sugar (sucrose); starch, particularly corn starch and sweet potato starch;
Examples thereof include polysaccharides such as wheat starch, and mixtures thereof.

The organic solvent used in the present invention may be any organic solvent that has a higher boiling point than water and is not compatible with water. However, even if it is a natural product and remains in the resin, it has no adverse effect on the environment or the human body. Less D-limonene is preferred.

[0021]

The present invention will be described below in more detail with reference to Examples and Comparative Examples. (Example 1) 1 mol (100 g) of 90% L-lactic acid and 8
5% phosphoric acid aqueous solution 0.05w% (50mg) 500m
and stirred under heating at 190 ° C. for 30 hours under reduced pressure. When the weight average molecular weight (Mw) of the obtained polylactic acid was measured, it was 19,000.

The weight average molecular weight of the obtained resin was measured by using gel permeation chromatography (GPC). The solvent used was chloroform, and the temperature was 40 ° C. and the flow rate was 1.0 ml / min. The GPC device is a high pressure pump (Model 510 for high-performance liquid chromatography) manufactured by Nippon Millipore Limited, a differential refractive index detector (Showex RI-71) manufactured by Showa Denko KK, and columns (GPC K802.5 and GPC) manufactured by the company.
K806M). The molecular weight is a value obtained by converting polystyrene as a standard sample.

(Example 2) 1 mol of 90% L-lactic acid (1 mol
00g) and 0.1% by weight of 85% phosphoric acid aqueous solution (100 m
g) was placed in a 500 ml reactor, and heated and stirred under reduced pressure at 190 ° C. for 30 hours. The weight average molecular weight of the obtained polylactic acid was 38,000.

Example 3 1 mol of 90% L-lactic acid (1 mol
00g) and 0.2% by weight of an 85% phosphoric acid aqueous solution (200 m
g) was placed in a 500 ml reactor, and heated and stirred under reduced pressure at 190 ° C. for 30 hours. The weight average molecular weight of the obtained polylactic acid was 29,000.

Example 4 1 mol of 90% L-lactic acid (1 mol
00g), 100 mg of corn starch and 0.1 w% (100 mg) of an 85% phosphoric acid aqueous solution were placed in a 500 ml reactor, and heated and stirred under reduced pressure at 190 ° C. for 30 hours. The weight average molecular weight of the obtained lactic acid-sugar copolymer is 51,000.
Met.

Example 5 1 mol of 90% L-lactic acid (1 mol
00g), 200 mg of corn starch and 0.1 w% (100 mg) of an 85% phosphoric acid aqueous solution were put into a 500 ml reactor, and heated and stirred under reduced pressure at 190 ° C. for 30 hours. The weight average molecular weight of the obtained lactic acid-sugar copolymer is 58,000.
Met.

Comparative Example 1 mol of 90% L-lactic acid (10 mol
0 g) was placed in a 500 ml reactor and heated and stirred at 190 ° C. for 30 hours under reduced pressure. The weight average molecular weight of the obtained polylactic acid was 11,000.

[0028]

As described above, according to the present invention, by using a phosphoric acid derivative as a polymerization catalyst for a hydroxycarboxylic acid or a mixture of a hydroxycarboxylic acid and a saccharide or a metal oxide, it is not recovered after use. Even if disposed of in the natural environment, it has little effect on the environment.

The obtained resin is used not only for the same purpose as the resin synthesized using an ordinary catalyst, but also for medical resin molded articles which come into direct contact with the living body. Can be.

Claims (5)

[Claims] 1. A phosphoric acid derivative as a polymerization catalyst in one kind of hydroxycarboxylic acid, a mixture of two or more kinds of hydroxycarboxylic acids, a mixture of hydroxycarboxylic acids and saccharides, or a mixture of hydroxycarboxylic acids and metal oxides. A method for producing a polyhydroxycarboxylic acid, comprising adding and stirring under heating under reduced pressure, or performing azeotropic dehydration polymerization in an organic solvent. 2. The polyhydroxycarboxylic acid according to claim 1, wherein the phosphoric acid derivative is at least one phosphoric acid derivative selected from the group consisting of phosphoric acid, pyrophosphoric acid, polyphosphoric acid and phosphorus acetate. Manufacturing method. 3. The method for producing a polyhydroxycarboxylic acid according to claim 1, wherein the hydroxycarboxylic acid is lactic acid, glycolic acid, tartaric acid, citric acid, malic acid, or a mixture thereof. 4. The method for producing a polyhydroxycarboxylic acid according to claim 1, wherein the saccharide is a polysaccharide. 5. The method for producing polyhydroxycarboxylic acid according to claim 1, wherein the organic solvent is D-limonene.