JPH051142A - Method for lowering molecular weight of aliphatic polyester - Google Patents

Abstract

(57) [Summary] [Structure] A high-molecular-weight aliphatic polyester is reduced in molecular weight by an alcoholysis reaction with an alcohol using metal alkoxide as a catalyst. [Effects] Unlike other methods for reducing the molecular weight, this method for reducing the molecular weight can reduce the molecular weight without broadening the molecular weight distribution, and is therefore advantageous in controlling the biodegradation rate.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for reducing the molecular weight of a high molecular weight aliphatic polyester, particularly a high molecular weight aliphatic polyester produced by a microorganism, without broadening its molecular weight distribution. This makes it possible to control the decomposition rate of the aliphatic polyester in a decomposition environment, and to manufacture an aliphatic polyester having a low molecular weight that matches the application. In addition, the low molecular weight aliphatic polyester can also be used as a new biodegradable plastic raw material.

[0002]

2. Description of the Related Art Aliphatic polyester is a polymer known to have excellent biodegradability and biocompatibility, and various studies have been conducted on its application as a material for medical use, agricultural use and environmental protection. Poly- produced by microorganisms
3-hydroxybutyrate (hereinafter referred to as P3HB)
And copolymers of 3-hydroxybutyrate, eg 3
-Hydroxybutyrate and 3-hydroxyvalerate copolymer (hereinafter referred to as P3HB-P3HV), 3
A copolymer of -hydroxybutyrate and 4-hydroxybutyrate (hereinafter referred to as P3HB-P4HB) and the like have excellent biodegradability, biodegradability (absorption), biocompatibility, gas permeation resistance, and heat resistance. As a polymer exhibiting plasticity, application to surgical sutures and fixing materials for fractures, sustained-release systems for drugs such as pharmaceuticals and agricultural chemicals, and food packaging films utilizing gas permeation resistance will be actively tried in recent years. Is becoming.

However, a polymer produced by a microorganism has a large molecular weight of several hundreds of thousands to one million, and is not decomposed immediately even in a decomposition environment and remains for a considerable period of time. In particular, the rate of decomposition in vivo is very slow, and despite its excellent properties, it has not yet been used in the medical field. Generally, the weight loss of polyesters depends on the degradation rate and the molecular weight. On the other hand, the mechanical properties hardly change when the molecular weight is tens of thousands or more. Therefore, in order to control the rate of weight reduction due to the decomposition of polyester, in particular, to accelerate the decomposition in vivo, the molecular weight may be reduced to about tens of thousands, which is equivalent to that of synthetic polymers.

An existing technique for lowering the molecular weight of polyesters is a method of hydrolysis in the presence of an acid or alkali catalyst. However, when this method is applied to P3HB, it is insoluble in water because P3HB is a hydrophobic polymer,
Since the solid-liquid two-phase decomposition does not occur uniformly, the molecular weight distribution is broad and it is difficult to control the molecular weight. An improvement in this respect is shown in JP-A-57-45131. This is a method of hydrolyzing P3HB by mixing an organic phase in which P3HB is dissolved and an aqueous phase containing an acid catalyst in a suspension state, heating and refluxing the solvent.
Since it is a liquid two-phase system, it is closer to a homogeneous system than in the case of a solid two-phase system. However, even with this method, the spread of the molecular weight distribution cannot be avoided.

Generally, when the molecular weight of a high molecular weight substance is lowered, the dispersity increases, but in the case of an aliphatic polyester which is expected to be biodegradable, the increase of the dispersity is disadvantageous particularly in controlling the biodegradation rate. That is, when the degree of dispersion is high, in order to control the biodegradation rate to a desired value, it is necessary to obtain one having a molecular weight within a certain range by separation or purification, which is very disadvantageous from the viewpoint of the yield of raw materials and the simplification of the process. is there. On the other hand,
As disclosed in JP-A-64-27483, a method for directly producing a low molecular weight polyester by a microorganism has also been proposed. This method is used for P3 by a bacterium belonging to the genus Protomonas.
The present invention relates to a technique for producing HB and has succeeded in producing P3HB having a molecular weight of tens of thousands as far as P3HB is concerned. However, Protomonas bacteria can only produce P3HB, and P3HB- produced by Alcaligenes and the like.
P3HV (JP-A-61-293385) and P3HB-P4H
Copolymers such as B (JP-A-63-269989) cannot be produced. Therefore, the above method cannot be applied to lower the molecular weight of these polymers, and is not versatile.

[0006]

As described above, according to the conventional method for reducing the molecular weight of an aliphatic polyester, the molecular weight of various aliphatic polyesters can be increased without widening the molecular weight distribution (without increasing the dispersity). Can not be lowered. An object of the present invention is to produce an aliphatic polyester which can be reduced in molecular weight without broadening the molecular weight distribution of various aliphatic polyesters and whose decomposition rate can be controlled.

[0007]

DISCLOSURE OF THE INVENTION The inventors of the present invention, by alcoholyzing a high molecular weight aliphatic polyester, particularly a polyester produced by a microorganism, using a metal alkoxide as a catalyst, without broadening the molecular weight distribution of this polyester. The inventors have found that the molecular weight can be reduced and have completed the present invention. That is, the gist of the present invention resides in a method for reducing the molecular weight of an aliphatic polyester, which comprises reacting an aliphatic polyester with an alcohol using a metal alkoxide as a catalyst. In a preferred embodiment, the aliphatic polyester is a microbially produced polyester.

[0008]

The polyester to which the method of lowering the molecular weight of the present invention can be applied is an aliphatic polyester having a main chain of an aliphatic group, and is particularly preferably applied to an aliphatic polyester produced by a microorganism. Examples of microorganisms that produce aliphatic polyester include Alcaligenes eutrophus, Bacillus megateriu
m, Beijerinckia indica, Derxia gummosa , Methylobac
terium , Pseudomonas cepacia, Pseudomonas aerugino
sa , Pseudomonas fluorescens, Pseudomonas oleovora
ns , Pseudomonas putida , Pseudomonastestosteronii,
Many microorganisms such as Rhodaspirillium rubrum and Alcaligenes latus can be exemplified, but the origin is not limited in the present invention, and a crude product or a purified product obtained from the microorganism by any known separation means can be used. Examples of such aliphatic polyesters include P
3HB, P3HB-P3HV, P3HB-P4HB, and other polymers and copolymers obtained by condensation of an aliphatic hydroxy acid can be mentioned. For an aliphatic polyester obtained by condensation of an aliphatic diol and an aliphatic dicarboxylic acid, However, the present invention can be applied.

The metal alkoxide used as a catalyst in the method of lowering the molecular weight of the present invention is preferably an alkoxide of titanium, tin or zirconium. Specific examples of these metal alkoxides include tetraalkyl titanates such as tetrabutyl titanate, tin alkoxides such as dibutyltin oxide and monobutyltin oxide, zirconium alkoxides such as zirconium tetrabutoxide and zirconium isopropoxide. To be Alcohols used in the method of the present invention include aliphatic alcohols such as methanol, ethanol, propanol, butanol, aromatic alcohols such as benzyl alcohol, halogen-substituted alcohols such as hexafluoroisopropanol, and the like. You may mix and use several kinds of alcohol.

The proportions of the aliphatic polyester, the metal alkoxide and the alcohol used vary depending on the molecular weight and the rate of reduction of the molecular weight of the aliphatic polyester to be reduced in molecular weight.
The metal alkoxide is 0.1 to 20, preferably 1 to 10, and the alcohol is 1 to 1000, preferably 10 to 200. If the metal alkoxide is 0.1 or less, the reaction does not proceed sufficiently, and if it is 20 or more, the amount of the catalyst is too large, which is not economical. If the alcohol content is 1 or less, alcoholysis does not proceed sufficiently, and if the alcohol content is 1000 or more, the alcohols are used more than necessary, which is not economical.

The reaction conditions are not particularly limited, so long as the molecular weight reduction by cleavage of the polyester is achieved. For example, it can be carried out by heating and stirring a mixture containing the aliphatic polyester, the metal alkoxide and the alcohol in the above proportions. In this case, the reaction temperature is usually
The temperature is 80 to 200 ° C, preferably 100 to 180 ° C. If the reaction temperature is 80 ° C or lower, the reaction rate is extremely reduced, which is not economical. Further, if the temperature is 200 ° C. or higher, the aliphatic polyester is thermally decomposed and the molecular weight distribution is widened, which is not preferable.

The reaction time varies depending on the reaction temperature, the molecular weight of the polyester used and the desired molecular weight of the polyester after the reaction, but is preferably 0.2 to 50 hours.
If it is less than 0.2 hours, the reaction is not sufficient, and if it is more than 50 hours, it is not economical and unfavorable side reactions occur. The reaction may be performed using a solvent, and usable solvents include aromatic compounds such as benzene, toluene and xylene, higher aliphatic compounds such as hexadecane, aromatic halides such as dichlorobenzene and chlorobenzene, dichloromethane and chloroform. , Dichloroethane, trichloroethane and the like are halogen-substituted aliphatic compounds. When alcohol used for alcoholysis is propanol, butanol, etc., the reaction proceeds sufficiently even without using a solvent, since it has a relatively high boiling point.

The reaction product is recovered by cooling the reaction mixture or adding a poor solvent for the aliphatic polyester to the reaction mixture to precipitate the polyester, and then performing solid-liquid separation operations such as centrifugation and filtration. It can be carried out and low molecular weight aliphatic polyesters can be obtained. Examples of the poor solvent for the aliphatic polyester include alcohols such as methanol and ethanol, lower aliphatic compounds such as hexane and heptane, ethers such as diethyl ether, and esters such as ethyl acetate. According to the method of the present invention, when formed into a molded article, it is possible to easily produce an aliphatic polyester whose molecular weight is controlled so that the decomposition rate by organisms or in vivo is moderate by adjusting the reaction conditions. In addition, because it has excellent biocompatibility, gas permeation resistance, and thermoplasticity, it is practically used as a suture and fracture fixation material for surgery, a sustained release system for drugs such as pharmaceuticals and agricultural chemicals, and a film for food packaging. It can be applied to. Hereinafter, the present invention will be specifically described with reference to examples.

[0014]

[Example 1] 0.43 g of P3HB, 20 ml of dichlorobenzene, 5 ml of propanol and 0.017 g of tetrabutoxytitanium produced by a microorganism were charged into a pressure-resistant autoclave, the inside of the autoclave was replaced with nitrogen, and the mixture was heated with stirring to react. The reaction was carried out at a temperature of 150 ° C for 4 hours. After cooling, the reaction mixture was poured into 500 ml of methanol with stirring, the precipitate was filtered and thoroughly dried under reduced pressure to obtain 0.44 g of white product. The molecular weight was analyzed by gel permeation chromatography using chloroform as the eluent, and the results shown in Table 1 were obtained. The molecular weight was calculated in terms of polystyrene. As is clear from Table 1, according to the method of the present invention, the molecular weight could be lowered without broadening the molecular weight distribution (dispersion degree). However, the dispersity was calculated by the following formula. Polydispersity = weight average molecular weight / number average molecular weight

[0015]

[Table 1]

[0016]

Example 2 Using 0.43 g of P3HB produced by a microorganism, 20 ml of propanol and 0.017 g of tetrabutoxytitanium, a reaction was carried out under the same conditions as in Example 1. The results are shown in Table 2. As is apparent from this, according to the method of the present invention, the molecular weight could be reduced without broadening the molecular weight distribution.

[0017]

[Table 2]

[0018]

As described above, according to the present invention, it is possible to provide a method for lowering the molecular weight of an aliphatic polyester without increasing the dispersity. Therefore, by adjusting the reaction conditions, it is possible to control the molecular weight of the product in a single step without separation / purification after lowering the molecular weight, so that the biodegradability is controlled. It is possible to produce a useful low-molecular-weight aliphatic polyester which is excellent in use and is suitable for applications such as medical care and food packaging.

Claims (2)

[Claims] 1. A method for reducing the molecular weight of an aliphatic polyester, which comprises reacting an aliphatic polyester with an alcohol using a metal alkoxide as a catalyst. 2. The method according to claim 1, wherein the aliphatic polyester is a polyester synthesized by a microorganism.