JP7209434B2 - Method for producing polyhydroxyalkanoic acid and use thereof - Google Patents

Description

The present invention relates to a method for producing polyhydroxyalkanoic acid and its use.

Polyhydroxyalkanoic acid (hereinafter sometimes referred to as "PHA") is known to be biodegradable.

PHAs produced by microorganisms are accumulated in the cells of microorganisms, so in order to use PHAs as plastics, a process of separating and purifying PHAs from the cells of microorganisms is required. In the step of separating and purifying PHA, the cells of PHA-containing microorganisms are crushed or biological components other than PHA are solubilized, and then PHA is taken out from the resulting aqueous suspension. At this time, for example, separation operations such as centrifugation, filtration, and drying are performed. A spray dryer, a fluidized bed dryer, a drum dryer, or the like is used for the drying operation, and the spray dryer is preferably used because of its simple operation.

So far, the present inventors have used polyvinyl alcohol (PVA) as a dispersant before adjusting the pH of the aqueous suspension to 7 or less in order to prevent the aggregation of PHA in the aqueous suspension of pH 7 or less. We have developed a technique of adding the water and then spray-drying the resulting aqueous suspension having a pH of 7 or less (see Patent Document 1).

WO2018/070492

Although the technique of Patent Document 1 described above is excellent, there is room for further improvement.

Accordingly, an object of the present invention is to provide a method for producing PHA (for example, PHA powder) with high productivity.

The present inventors have made intensive studies to solve the above problems, and found that the use of a specific dispersant can prevent aggregation of PHA when adjusting the pH of an aqueous suspension to 7 or less, In addition, the present inventors have found new findings that adhesion to the shaft of an extruder can be suppressed during powder processing, and have completed the present invention.

Accordingly, one aspect of the present invention is the steps of (a) preparing an aqueous suspension comprising a polyhydroxyalkanoic acid and a dispersant and having a pH of 7 or less, and (b) the and spray drying the aqueous suspension, wherein the dispersant is composed of blocks of poly(ethylene oxide) (PEO) and hydrophobic groups, the PEO blocks in the dispersant being composed of ethylene oxide The present invention relates to a method for producing a polyhydroxyalkanoic acid, wherein (EO) has a repeating number of 20 or more.

Further, one aspect of the present invention is an aqueous suspension containing a polyhydroxyalkanoic acid and a dispersant and having a pH of 7 or less, wherein the dispersant is a block of poly(ethylene oxide) (PEO) , to an aqueous suspension composed of hydrophobic groups.

Further, one aspect of the present invention contains a dispersant composed of polyhydroxyalkanoic acid and poly(ethylene oxide) (PEO) blocks and hydrophobic groups, and has a bulk density of 0.30 to 0.30. It relates to a polyhydroxyalkanoic acid powder having a weight of 70 kg/L and a median particle size of 80 to 200 μm.

According to one aspect of the present invention, it is possible to provide a production method capable of obtaining PHA (for example, PHA powder) with high productivity.

FIG. 3 is a diagram showing the relationship between the amount of dispersant added and the volume median diameter in Examples, Comparative Examples, and Reference Examples. FIG. 2 is a diagram showing the relationship between the amount of EO in a dispersant and the thermal stability of PHA powder in Examples and Comparative Examples.

One embodiment of the present invention will be described in detail below. In this specification, unless otherwise specified, "A to B" representing a numerical range means "A or more and B or less". Also, all of the documents mentioned in this specification are incorporated herein by reference.

[1. Overview of the present invention]
A method for producing a polyhydroxyalkanoic acid according to one embodiment of the present invention (hereinafter referred to as "the present production method") includes (a) a polyhydroxyalkanoic acid and a dispersant, and has a pH of 7 or less. and (b) spray drying the aqueous suspension prepared in step (a), wherein the dispersant comprises poly(ethylene oxide) (PEO) blocks and , and a hydrophobic group, and the PEO block in the dispersant has 20 or more ethylene oxide (EO) repeats.

While further researching the production of PHA, the present inventors discovered a new problem in the above-mentioned method of Patent Document 1, in which the PHA powder adheres to the shaft in the extruder when the obtained PHA powder is processed. Found a problem. As a result of the present inventor's analysis of the cause, it was thought to be derived from PVA, which is a dispersant.

Therefore, the present inventors diligently studied a dispersant that prevents aggregation of PHA in an aqueous suspension having a pH of 7 or less and does not adhere to the shaft of an extruder during powder processing after drying. . As a result, by using a specific dispersant (specifically, a dispersant composed of poly(ethylene oxide) (PEO) blocks and hydrophobic groups), the pH of the aqueous suspension can be lowered to 7 or less. It was found that the aggregation of PHA can be prevented when adjusting to 2, and the adhesion to the shaft of the extruder during powder processing can also be suppressed.

Furthermore, in the course of the above studies, the present inventors surprisingly found that (i) the number of repeating units of EO in the dispersant is correlated with the thermal stability of the PHA powder after granulation, (ii) by using a dispersant containing a certain amount or more of EO, the PHA powder after drying has excellent thermal stability; and (iii) by using a dispersant containing a certain amount or more of EO, a It was found for the first time that aggregation of PHA in an aqueous suspension can be suppressed.

Therefore, according to this production method using a specific dispersant, it is possible to obtain PHA (for example, PHA powder) with high productivity. The configuration of this manufacturing method will be described in detail below.

[2. Production method of PHA]
This production method is a method including the following steps (a) and (b) as essential steps.
- Step (a): A step of preparing an aqueous suspension comprising a PHA and a dispersant and having a pH of 7 or less (wherein the dispersant is a block of poly(ethylene oxide) (PEO) and a hydrophobic and the PEO block in the dispersant has a repeating number of ethylene oxide (EO) of 20 or more.)
- Step (b): a step of spray-drying the aqueous suspension prepared in the step (a) (step (a))
In step (a) of the present production method, an aqueous suspension containing PHA and a specific dispersant and having a pH of 7 or less is prepared. In the aqueous suspension, the PHA is dispersed in the aqueous medium, and the dispersant is dissolved in the aqueous medium. Hereinafter, an aqueous suspension containing at least PHA may be abbreviated as "PHA aqueous suspension".

<PHA>
As used herein, "PHA" is a general term for polymers having hydroxyalkanoic acid as a monomer unit. The hydroxyalkanoic acid constituting PHA is not particularly limited, but examples include 3-hydroxybutanoic acid, 4-hydroxybutanoic acid, 3-hydroxypropionic acid, 3-hydroxypentanoic acid, 3-hydroxyhexanoic acid, 3-hydroxy heptanoic acid, 3-hydroxyoctanoic acid, and the like. These polymers may be homopolymers or copolymers containing two or more monomer units.

More specifically, PHA includes, for example, poly(3-hydroxybutyrate) (P3HB), poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (P3HB3HH), poly(3-hydroxybutyrate) -co-3-hydroxyvalerate) (P3HB3HV), poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3HB4HB), poly(3-hydroxybutyrate-co-3-hydroxyoctanoate) (P3HB3HO), Poly(3-hydroxybutyrate-co-3-hydroxyoctadecanoate) (P3HB3HOD), Poly(3-hydroxybutyrate-co-3-hydroxydecanoate) (P3HB3HD), Poly(3 -hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (P3HB3HV3HH) and the like. Among them, P3HB, P3HB3HH, P3HB3HV, and P3HB4HB are preferable because they are easy to produce industrially.

In addition, by changing the composition ratio of the repeating units, the melting point and crystallinity can be changed. A copolymer of 3-hydroxybutyric acid and 3-hydroxyhexanoic acid is used from the viewpoint that it is possible to impart it and that it is a plastic that is easy to produce industrially and has physical properties as described above. Some P3HB3HH are more preferred.

In one embodiment of the present invention, the composition ratio of the repeating units of P3HB3HH is 3-hydroxybutyrate unit/3-hydroxyhexanoate unit composition ratio of 80/20 to 80/20 from the viewpoint of balance between flexibility and strength. It is preferably 99/1 (mol/mol), more preferably 85/15 to 97/3 (mol/mol). When the composition ratio of 3-hydroxybutyrate units/3-hydroxyhexanoate units is 99/1 (mol/mol) or less, sufficient flexibility can be obtained, and when it is 80/20 (mol/mol) or more, If there is, sufficient hardness can be obtained.

Step (a) preferably includes the following steps (a1) and (a2).
- Step (a1): a step of adding a dispersant to the PHA aqueous suspension (here, the dispersant is composed of poly(ethylene oxide) (PEO) blocks and hydrophobic groups, and The PEO block of has a repeating number of ethylene oxide (EO) of 20 or more.)
- Step (a2): A step of adjusting the pH of the aqueous PHA suspension to 7 or less The order of performing the steps (a1) and (a2) is not particularly limited, but the PHA aggregation in the step (a2) It is preferable to carry out step (a2) after step (a1) from the viewpoint of obtaining an aqueous suspension that is suppressed and has more excellent dispersion stability of PHA.

In step (a), the PHA aqueous suspension (the PHA aqueous suspension to which no dispersing agent has been added) used as a starting material is not particularly limited, but for example, a microorganism capable of producing PHA in cells can be used. It can be obtained by a method comprising a culturing step of culturing and, after the culturing step, a purification step of decomposing and/or removing substances other than PHA.

In this production method, a step of obtaining an aqueous PHA suspension (an aqueous PHA suspension to which no dispersing agent has been added) (for example, a step including the above-described culturing step and purification step) is performed before step (a). may contain. Microorganisms used in this step are not particularly limited as long as they are capable of producing PHA in their cells. For example, microorganisms isolated from nature, microorganisms deposited with strain depositories (eg, IFO, ATCC, etc.), or mutants, transformants, etc. that can be prepared from them can be used. More specifically, for example, the genus Cupriavidus, the genus Alcaligenes, the genus Ralstonia, the genus Pseudomonas, the genus Bacillus, the genus Azotobacter, the genus Nocardia, the genus Aeromonas (Aeromonas) genus bacteria and the like. Among them, microorganisms belonging to the genus Aeromonas, Alcaligenes, Ralstonia, or Capriavidus are preferred. In particular, strains such as A. lipolytica, A. latus, A. caviae, A. hydrophila, and C. necator is more preferred, and Capriavidus neceta is most preferred.

In addition, in the case where the microorganism originally does not have a PHA-producing ability or the PHA-producing amount is low, the desired PHA synthase gene and/or a mutant thereof may be added to the microorganism. A transformant obtained by introduction can also be used. The PHA synthase gene used for the preparation of such a transformant is not particularly limited, but a PHA synthase gene derived from Aeromonas caviae is preferable. By culturing these microorganisms under appropriate conditions, it is possible to obtain microbial cells in which PHA is accumulated. Although the method for culturing the microbial cells is not particularly limited, for example, the method described in JP-A-05-93049 is used.

Since the PHA-containing microorganisms produced by culturing the above microorganisms contain a large amount of bacterial cell-derived components as impurities, a purification step for decomposing and/or removing impurities other than PHA is usually performed. can be implemented. This purification step is not particularly limited, and physical treatments, chemical treatments, biological treatments, etc. that can be considered by those skilled in the art can be applied. method is preferably applicable.

Since the amount of impurities remaining in the final product is generally determined by the above purification process, it is preferable to reduce these impurities as much as possible. Of course, depending on the application, impurities may be mixed as long as the physical properties of the final product are not impaired. However, when high-purity PHA is required, such as medical applications, impurities should be reduced as much as possible. preferable. As an indicator of the degree of purification at that time, for example, the amount of protein in the PHA aqueous suspension is exemplified. The amount of protein is preferably 30,000 ppm or less, more preferably 15,000 ppm or less, even more preferably 10,000 ppm or less, and most preferably 7,500 ppm or less based on PHA weight. Purification means are not particularly limited, and for example, the known methods described above can be applied.

The solvent (“solvent” is also referred to as “aqueous medium”) constituting the PHA aqueous suspension in this production method may be water or a mixed solvent of water and an organic solvent. Moreover, in the mixed solvent, the concentration of the organic solvent compatible with water is not particularly limited as long as it is equal to or less than the solubility of the organic solvent used in water. The organic solvent compatible with water is not particularly limited, but examples include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, iso-butanol, pentanol, hexanol, heptanol, and the like. ketones such as acetone and methyl ethyl ketone; ethers such as tetrahydrofuran and dioxane; nitriles such as acetonitrile and propionitrile; amides such as dimethylformamide and acetamide; Among them, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, iso-butanol, acetone, methyl ethyl ketone, tetrahydrofuran, dioxane, acetonitrile, propionitrile and the like are preferable because they are easy to remove. Methanol, ethanol, 1-propanol, 2-propanol, butanol, acetone and the like are more preferable because they are readily available. Furthermore, methanol, ethanol and acetone are particularly preferred. The aqueous medium constituting the PHA aqueous suspension may contain other solvents, components derived from bacterial cells, compounds generated during purification, etc., as long as they do not impair the essence of the present invention.

The aqueous medium constituting the PHA aqueous suspension in the present production method preferably contains water. The content of water in the aqueous medium is preferably 5% by weight or more, more preferably 10% by weight or more, still more preferably 30% by weight or more, and particularly preferably 50% by weight or more.

<Dispersant>
The dispersing agent in step (a) of the present manufacturing method is composed of poly(ethylene oxide) (PEO) blocks and hydrophobic groups, and the PEO blocks in the dispersing agent have the number of repeating ethylene oxide (EO) is 20 or more.

The dispersant in the step (a) of the production method has the characteristic structure as described above, so that it can prevent aggregation of PHA when adjusting the pH of the aqueous PHA suspension to 7 or less. In addition, it has the effect of suppressing adhesion to the shaft of the extruder during powder processing.

As used herein, the term "poly(ethylene oxide) (PEO) block" refers to the polymer portion formed by polymerization of ethylene oxide (EO) in the structure of the dispersant.

As used herein, "hydrophobic group" means a substituent that exhibits hydrophobic properties in the structure of the dispersant other than the poly(ethylene oxide) (PEO) block.

The dispersing agent in step (a) of the production method is not particularly limited as long as it is included in the above definition.

In one embodiment of the present invention, the repeating number of ethylene oxide (EO) in the PEO block in the dispersant may be 20 or more, preferably 22 or more, and more preferably 24 or more. In one embodiment of the present invention, the upper limit of the number of repetitions of ethylene oxide (EO) in the PEO block in the dispersant is, for example, 60 or less, preferably 55 or less, more preferably 50 It is below. If the number of repetitions of ethylene oxide (EO) is within the above range, the effect of maintaining the molecular weight of PHA when the PHA aqueous suspension is heated is exhibited.

In one embodiment of the present invention, the dispersant is preferably a compound represented by formula (1) below.

上記の式（１）において、Ｒは、例えば、炭素数が１～２０の炭化水素基であり、好ましくは、炭素数が２～２０の炭化水素基であり、より好ましくは、炭素数が５～２０の炭化水素基である。炭素数が、２０以下であると、ＰＨＡが水中に分散しやすくなり、炭素数が、１で以上あると、分散剤が疎水性を有する。炭化水素基は、直鎖状、分岐鎖状、環状のいずれの形態であってもよく、好ましくは、直鎖状であり、より好ましくは、直鎖状のアルキル基である。

In the above formula (1), R is, for example, a hydrocarbon group having 1 to 20 carbon atoms, preferably a hydrocarbon group having 2 to 20 carbon atoms, more preferably 5 carbon atoms. ∼20 hydrocarbon groups. When the number of carbon atoms is 20 or less, the PHA is easily dispersed in water, and when the number of carbon atoms is 1 or more, the dispersant has hydrophobicity. The hydrocarbon group may be linear, branched or cyclic, preferably linear, more preferably linear alkyl group.

In the above formula (1), n is, for example, 20-60, preferably 22-60, more preferably 25-60. When n is 60 or less, the dispersant has a low melting point and is easy to use.

The dispersant used in step (a) (especially step (a1)) of the present production method is not particularly limited, and for example, commercially available products can be used. Commercially available products include, for example, Emulsogen EPN 287 (manufactured by CLARIANT), Emulsogen LCN 407 (manufactured by CLARIANT), Neugen TDS (manufactured by Daiichi Kogyo Seiyaku), DKS NL (manufactured by Daiichi Kogyo Seiyaku), Neugen SD (manufactured by Daiichi Kogyo Seiyaku made) etc. can be used.

The amount of the dispersant added to the PHA aqueous suspension in step (a) (especially step (a1)) of the present production method is not particularly limited, but is 0 per 100 parts by weight of PHA contained in the aqueous suspension. .1 to 20 parts by weight is preferred, 0.5 to 10 parts by weight is more preferred, and 0.75 to 5 parts by weight is even more preferred. By setting the amount of the dispersant to be added within the above range, the dispersion stability of the PHA in the aqueous PHA suspension tends to be further improved, and the spray drying can be carried out more efficiently.

<Others>
The PHA aqueous suspension before being subjected to the step (a) of the present production method (the PHA aqueous suspension before the addition of the dispersing agent) is usually more than 7 by going through the above purification step. has a pH. Therefore, the pH of the PHA aqueous suspension is adjusted to 7 or less in step (a) (especially step (a2)) of the present production method. The adjustment method is not particularly limited, and includes, for example, a method of adding an acid. The acid is not particularly limited, and may be either an organic acid or an inorganic acid, and may or may not be volatile. More specifically, examples of acids that can be used include sulfuric acid, hydrochloric acid, phosphoric acid, and acetic acid.

Regarding the upper limit of the pH of the aqueous PHA suspension to be adjusted in the above adjustment step, from the viewpoint of reducing coloration when PHA is heated and melted and ensuring the stability of the molecular weight during heating and/or drying, it is 7. or less, preferably 5 or less, more preferably 4 or less. The lower limit of the pH is preferably 1 or more, more preferably 2 or more, and still more preferably 3 or more, from the viewpoint of acid resistance of the container. By adjusting the pH of the aqueous PHA suspension to 7 or less, it is possible to obtain a PHA with reduced coloration during heating and melting, and suppressed reduction in molecular weight during heating and/or drying.

In one embodiment of the invention, an aqueous suspension having a pH of 7 or less comprising a polyhydroxyalkanoic acid and a dispersant, said dispersant comprising blocks of poly(ethylene oxide) (PEO); An aqueous suspension is provided comprising a hydrophobic group.

The concentration of PHA in the aqueous PHA suspension obtained in step (a) of the present production method is economically advantageous from the standpoint of drying utility and improves productivity. % or more is more preferable, and 50% by weight or more is even more preferable. Further, the upper limit of the PHA concentration is preferably 65% by weight or less, more preferably 60% by weight or less, because it may result in the closest packing and sufficient fluidity may not be ensured. The method for adjusting the PHA concentration is not particularly limited, and includes methods such as adding an aqueous medium or removing a portion of the aqueous medium (for example, by removing the supernatant after centrifugation). . The adjustment of the PHA concentration may be carried out at any stage of step (a), or may be carried out at a stage prior to step (a).

In one embodiment of the present invention, in the present production method, the concentration of polyhydroxyalkanoic acid in the aqueous suspension prepared in step (a) is 30% by weight or more and 65% by weight or less.

The volume median diameter of the PHA in the PHA aqueous suspension obtained by the step (a) of the present production method (hereinafter simply referred to as "the volume median diameter of the PHA") is the volume median diameter of the primary particles of the PHA (hereinafter , referred to as “primary particle size”) is preferably 50 times or less, more preferably 20 times or less, and even more preferably 10 times or less. Since the volume median diameter of the PHA is 50 times or less the primary particle diameter, the PHA aqueous suspension exhibits better fluidity, so that the subsequent step (b) can be carried out with high efficiency. productivity tends to improve further.

In one embodiment of the present invention, the volume median diameter of PHA is preferably 0.5 to 5 μm, more preferably 1 to 4.5 μm, more preferably 1 to 4 μm, from the viewpoint of achieving excellent fluidity. More preferred. The volume median diameter of PHA is measured by the method described in Examples.

The volume median diameter of the PHA can be used as an index of the dispersed state of the PHA in the PHA aqueous suspension. The method for adjusting the volume median diameter of the PHA is not particularly limited, and known means (stirring, etc.) can be applied. For example, for a PHA aqueous suspension that has lost its dispersed state due to exposure to acidic conditions (for example, when step (a2) is performed before step (a1)), a person skilled in the art can be subjected to physical treatment, chemical treatment, biological treatment, etc., to restore the PHA in the PHA aqueous suspension to a dispersed state (for example, the above state having the volume median diameter of PHA). .

(Step (b))
In step (b) in this production method, the aqueous PHA suspension prepared in step (a) is spray-dried. Examples of the spray-drying method include a method in which an aqueous PHA suspension is supplied in the form of fine droplets into a dryer, and the droplets are dried while being brought into contact with hot air in the dryer. The method (atomizer) for supplying the PHA aqueous suspension in the form of fine droplets into the dryer is not particularly limited, and includes known methods such as a method using a rotating disk and a method using a nozzle. The method of contacting the droplets with the hot air in the dryer is not particularly limited, and examples thereof include a parallel flow method, a countercurrent method, and a method using these methods in combination.

The drying temperature during the spray drying in the step (b) may be a temperature at which most of the aqueous medium can be removed from the droplets of the PHA aqueous suspension, and the droplets can be dried to the desired moisture content, and Conditions can be appropriately set so as not to cause quality deterioration (molecular weight reduction, color tone reduction, etc.), melting, etc. as much as possible. For example, the temperature of the hot air blown into the spray dryer can be appropriately selected within the range of 100 to 300°C. Also, the amount of hot air in the dryer can be appropriately set according to, for example, the size of the dryer.

This production method may include a step of further drying the obtained PHA (PHA powder, etc.) after the step (b) (for example, a step of drying under reduced pressure, etc.). In addition, the production method may include other steps (for example, a step of adding various additives to the PHA aqueous suspension, etc.).

According to this production method, a dry PHA having excellent thermal stability can be obtained with high productivity. In addition, according to this manufacturing method, it is possible to reduce the cost (equipment cost, utilities, etc.) of the drying process. Furthermore, according to this production method, it is possible to obtain PHA in the form of powder, so that PHA with excellent handleability can be obtained with high efficiency.

[3. Polyhydroxyalkanoic acid powder]
The polyhydroxyalkanoic acid powder according to one embodiment of the present invention (hereinafter referred to as "this PHA powder") comprises polyhydroxyalkanoic acid and poly(ethylene oxide) (PEO) blocks and hydrophobic groups. and has a bulk density of 0.3 to 0.5 kg/L and a median particle size of 80 to 200 μm.

The present PHA powder is produced by the present production method, and therefore has the advantage of being excellent in thermal stability.

In this embodiment, the above-described "polyhydroxyalkanoic acid" and "dispersant" are used.

The bulk density of the PHA powder is not particularly limited, but is preferably 0.30 to 0.70 kg/L, more preferably 0.35 to 0.60 kg/L, from the viewpoint of achieving excellent fluidity. , 0.40 to 0.55 kg/L are more preferred. The bulk density of the present PHA powder is measured by the method described in Examples.

The median particle size of the present PHA powder is not particularly limited, but is preferably 80 to 200 μm, more preferably 100 to 180 μm, and more preferably 120 to 170 μm from the viewpoint of achieving excellent fluidity. The median particle size of the present PHA powder is measured by the method described in Examples.

The present PHA powder may contain the dispersant described above. The content of the dispersant in the PHA powder is not particularly limited, but is preferably 0.1 to 20 parts by weight, more preferably 0.5 to 10 parts by weight, relative to 100 parts by weight of PHA constituting the PHA powder. , more preferably 0.75 to 5 parts by weight. By setting the amount of the dispersant to be added within the above range, the productivity of the PHA powder tends to be further improved.

Moreover, the present PHA powder may contain various components generated or not removed during the course of the present production method as long as the effects of the present invention are exhibited.

The present PHA powder can be used in various applications such as paper, film, sheet, tube, plate, stick, container (for example, bottle container, etc.), bag, and parts.

The present invention is not limited to the above-described embodiments, but can be modified in various ways within the scope of the claims, and can be obtained by appropriately combining technical means disclosed in different embodiments. is also included in the technical scope of the present invention.

That is, one embodiment of the present invention includes the following inventions.
<1> (a) a step of preparing an aqueous suspension containing a polyhydroxyalkanoic acid and a dispersant and having a pH of 7 or less, and (b) the aqueous suspension prepared in step (a) spray drying,
the dispersant is composed of poly(ethylene oxide) (PEO) blocks and hydrophobic groups;
The method for producing a polyhydroxyalkanoic acid, wherein the PEO block in the dispersant has a repeating number of ethylene oxide (EO) of 20 or more.
<2> The method for producing a polyhydroxyalkanoic acid according to <1>, wherein the dispersant is a compound represented by the following formula (1).

（式中、Ｒは、炭素数が１～２０の炭化水素基であり、ｎは、２０～６０である。）
＜３＞前記工程（ａ）で調製する水性懸濁液におけるポリヒドロキシアルカン酸の濃度が、３０重量％以上６５重量％以下である、＜１＞または＜２＞に記載のポリヒドロキシアルカン酸の製造方法。
＜４＞ポリヒドロキシアルカン酸および分散剤を含み、かつ、ｐＨが７以下である水性懸濁液であり、前記分散剤が、ポリ（エチレンオキサイド）（ＰＥＯ）のブロックと、疎水性基とから構成される水性懸濁液。
＜５＞ポリヒドロキシアルカン酸、およびポリ（エチレンオキサイド）（ＰＥＯ）のブロックと疎水性基とから構成される分散剤を含み、かつ、嵩密度が０．３０～０．７０ｋｇ／Ｌであり、メジアン粒子径が８０～２００μｍであるポリヒドロキシアルカン酸粉体。

(Wherein, R is a hydrocarbon group having 1 to 20 carbon atoms, and n is 20 to 60.)
<3> The polyhydroxyalkanoic acid according to <1> or <2>, wherein the concentration of the polyhydroxyalkanoic acid in the aqueous suspension prepared in the step (a) is 30% by weight or more and 65% by weight or less. Production method.
<4> An aqueous suspension containing a polyhydroxyalkanoic acid and a dispersant and having a pH of 7 or less, wherein the dispersant comprises a block of poly(ethylene oxide) (PEO) and a hydrophobic group An aqueous suspension comprising:
<5> contains a polyhydroxyalkanoic acid and a dispersant composed of a poly(ethylene oxide) (PEO) block and a hydrophobic group, and has a bulk density of 0.30 to 0.70 kg/L; A polyhydroxyalkanoic acid powder having a median particle size of 80 to 200 μm.

EXAMPLES The present invention will be described in more detail below based on examples, but the present invention is not limited to these examples.

[Measurement and evaluation method]
Measurements and evaluations in Examples and Comparative Examples were carried out by the following methods.

(Thermal stability)
As evaluation samples, PHA powders obtained in the following examples and comparative examples were used. This PHA powder was preheated at 160° C. for 7 minutes and then heated for 20 minutes to prepare a PHA sheet. After dissolving 10 mg of this PHA sheet in 10 ml of chloroform, insoluble matter was removed by filtration. This solution (filtrate) was subjected to molecular weight measurement using a Shimadzu GPC system equipped with "Shodex K805L (300×8 mm, two connected)" (manufactured by Showa Denko) using chloroform as a mobile phase. Commercially available standard polystyrene was used as a molecular weight standard sample. The molecular weight of the PHA powder was also measured in the same manner as described above, except that the PHA sheet was not prepared.

The thermal stability was evaluated using the molecular weight retention ratio (weight average molecular weight of PHA sheet/weight average molecular weight of PHA powder×100) obtained by applying heat at 160° C. for 20 minutes as an indicator. was 70% or more, the thermal stability was judged to be good. If the molecular weight retention was less than 70%, the thermal stability was judged to be poor.

(volume median diameter)
The particle size in the PHA aqueous suspension was measured using a HORIBA laser diffraction/scattering particle size distribution analyzer LA-950.

(median particle size)
The average particle size of the spray-dried PHA powder obtained by this production method was measured by the following method.

The average particle size was measured using a laser diffraction/scattering particle size distribution analyzer LA-950 (HORIBA). As a specific measurement method, 0.05 g of sodium dodecyl sulfate, which is a surfactant as a dispersant, was added to 20 mL of ion-exchanged water to obtain an aqueous surfactant solution. Thereafter, 0.2 g of the resin particle group to be measured was added to the surfactant aqueous solution, and the resin particle group was dispersed in the surfactant aqueous solution to obtain a dispersion liquid for measurement. The prepared dispersion was introduced into the above laser diffraction/scattering particle size distribution analyzer and measured.

(The bulk density)
The bulk density of PHA powder was measured by the following method. That is, by the method described in JIS K-7365, a funnel with a bottom opening of 20 mm to 30 mm is placed at the top of a metal cylinder (receptacle) with a volume of 100 ml ± 0.5 ml and an inner diameter of 45 mm ± 5 mm with a smooth inner surface. Measurement was performed using an apparatus in which a damper (for example, a metal plate) was set on the . A balance capable of measuring to the order of 0.1 g was used. As a specific measurement method, first, the funnel and the cylinder were held vertically so that the axes of the funnel and the cylinder were aligned. The PHA powder was mixed well prior to measurement. Next, the damper at the bottom opening of the funnel was closed, and 110-120 ml of PHA powder was put into it. After that, the damper was quickly pulled out, and the PHA powder was allowed to flow down into the receiver. When the receiver was full, the PHA powder that had risen from the receiver was scraped off with a straight plate. A balance was used to weigh the contents of the receiver to the nearest 0.1 g. The PHA powder to be measured was measured twice. The apparent bulk density (unit: kg/L) of the measured PHA powder was calculated by the following formula.
m/V
where m represents the mass of the contents of the receptacle (g) and V represents the volume of the receptacle (ml) (ie 100 in this measurement). Arithmetic mean value of two measurement results was used as the result.

[Example 1]
(Preparation of cell culture solution)
Ralstonia eutropha KNK-005 strain described in paragraph [0049] of International Publication No. 2008/010296 is cultured by the method described in paragraphs [0050] to [0053] of the same document, and PHA-containing cells are obtained. A cell culture solution containing Ralstonia eutropha is now classified as Capriavidus neceta.

(sterilization)
The cell culture solution obtained above was heated and stirred at an internal temperature of 60 to 80° C. for 20 minutes for sterilization.

(High pressure crushing treatment)
0.2% by weight of sodium dodecylsulfate was added to the sterilized cell culture solution obtained above. Furthermore, after adding sodium hydroxide aqueous solution so that pH might be set to 11.0, it heat-retained at 50 degreeC for 1 hour. After that, high-pressure crushing was performed at a pressure of 450 to 550 kgf/cm ² using a high-pressure crusher (high-pressure homogenizer model PA2K manufactured by Nirosoavi).

(refinement treatment)
An equal amount of distilled water was added to the crushed liquid obtained above after high-pressure crushing. After centrifugation, the supernatant was removed and concentrated twice. To this concentrated PHA aqueous suspension, the same amount of sodium hydroxide aqueous solution (pH 11.0) as the removed supernatant was added and centrifuged. Next, after removing the supernatant, add water again to suspend, add 0.2% by weight of sodium dodecyl sulfate and 1/100 weight of PHA of protease (Esperase, manufactured by Novozyme), The mixture was stirred for 2 hours while maintaining the pH at 10.0 and 50°C. After that, the supernatant was removed by centrifugation and concentrated 4-fold. By further adding water, the PHA concentration was adjusted to 48% by weight.

To the PHA aqueous suspension obtained above (solid content concentration 48%), 1 phr of the dispersant (trade name Emulsogen EPN 287, manufactured by CLARIANT) shown in Table 1 (per 100 parts by weight of PHA present in the aqueous suspension) was added. 1 part by weight) was added, and then the solid content concentration was adjusted to 46%. After the liquid was stirred for 30 minutes, sulfuric acid was added to adjust the pH to 3.3. The PHA aqueous suspension thus obtained was spray-dried using an ODT-70 type spray dryer manufactured by Okawara Co., Ltd. (hot air temperature: 125°C, exhaust air temperature: 80°C). The volume median size of PHA in the above aqueous suspension, and the thermal stability, median particle size and bulk density of PHA powder were measured and/or evaluated by the methods described above. Table 2 shows the results.

[Example 2]
A PHA aqueous suspension with a solid content concentration of 52% was prepared by the same operation as in Example 1 up to the purification treatment. Next, 0.5 phr of a dispersant (trade name: Emulsogen EPN 287, manufactured by Clariant) shown in Table 1 was added to the PHA aqueous suspension (solid content concentration: 52%), and then the solid content concentration was adjusted to 50%. . After the liquid was stirred for 30 minutes, sulfuric acid was added to adjust the pH to 4. The PHA aqueous suspension thus obtained was subjected to spray drying in the same manner as in Example 1. The volume median size of PHA in the above aqueous suspension, and the thermal stability, median particle size and bulk density of PHA powder were measured and/or evaluated by the methods described above. Table 2 shows the results.

[Example 3]
A PHA aqueous suspension with a solid content concentration of 52% was prepared by the same operation as in Example 1 up to the purification treatment. Next, 0.75 phr of a dispersant (trade name: Emulsogen EPN 287, manufactured by Clariant) shown in Table 1 was added to the PHA aqueous suspension (solid content concentration: 52%), and then the solid content concentration was adjusted to 50%. . After the liquid was stirred for 30 minutes, sulfuric acid was added to adjust the pH to 4. The PHA aqueous suspension thus obtained was subjected to spray drying in the same manner as in Example 1. The volume median size of PHA in the above aqueous suspension, and the thermal stability, median particle size and bulk density of PHA powder were measured and/or evaluated by the methods described above. Table 2 shows the results.

[Example 4]
A PHA aqueous suspension with a solid content concentration of 46% was prepared by the same operation as in Example 1 up to the purification treatment. Next, 5 phr of a dispersant (trade name: Emulsogen EPN 287, manufactured by Clariant) shown in Table 1 was added to the PHA aqueous suspension (solid content concentration: 46%), and then the solid content concentration was adjusted to 44%. After the liquid was stirred for 30 minutes, sulfuric acid was added to adjust the pH to 3.3. The PHA aqueous suspension thus obtained was subjected to spray drying in the same manner as in Example 1. The volume median size of PHA in the above aqueous suspension, and the thermal stability, median particle size and bulk density of PHA powder were measured and/or evaluated by the methods described above. Table 2 shows the results.

[Example 5]
A PHA aqueous suspension with a solid content concentration of 52% was prepared by the same operation as in Example 1 up to the purification treatment. Next, 1 phr of a dispersant (trade name: Emulsogen LCN 407, manufactured by Clariant) shown in Table 1 was added to the PHA aqueous suspension (solid content concentration: 52%), and then the solid content concentration was adjusted to 50%. After the liquid was stirred for 30 minutes, sulfuric acid was added to adjust the pH to 4. The PHA aqueous suspension thus obtained was subjected to spray drying in the same manner as in Example 1. The volume median size of PHA in the above aqueous suspension, and the thermal stability, median particle size and bulk density of PHA powder were measured and/or evaluated by the methods described above. Table 2 shows the results.

[Example 6]
A PHA aqueous suspension with a solid content concentration of 52% was prepared by the same operation as in Example 1 up to the purification treatment. Next, 0.75 phr of a dispersant shown in Table 1 (trade name Emulsogen LCN 407, manufactured by Clariant) was added to the PHA aqueous suspension (solid content concentration 52%), and then the solid content concentration was adjusted to 50%. . After the liquid was stirred for 30 minutes, sulfuric acid was added to adjust the pH to 4. The PHA aqueous suspension thus obtained was subjected to spray drying in the same manner as in Example 1. The volume median size of PHA in the above aqueous suspension, and the thermal stability, median particle size and bulk density of PHA powder were measured and/or evaluated by the methods described above. Table 2 shows the results.

[Comparative Example 1]
A PHA aqueous suspension with a solid content concentration of 52% was prepared by the same operation as in Example 1 up to the purification treatment. Next, 0.42 phr of a dispersant (trade name: Emulsogen EPA 073, manufactured by Clariant) shown in Table 1 was added to the PHA aqueous suspension (solid content concentration: 52%), and then the solid content concentration was adjusted to 50%. . After the liquid was stirred for 30 minutes, sulfuric acid was added to adjust the pH to 4. The volume median diameter of PHA in the aqueous suspension and the thermal stability of the PHA powder were measured and/or evaluated by the methods described above. Table 2 shows the results. The volume median diameter of PHA in the aqueous suspension could not be measured because the viscosity of the aqueous suspension became too high.

[Comparative Example 2]
A PHA aqueous suspension with a solid content concentration of 52% was prepared by the same operation as in Example 1 up to the purification treatment. Next, 1.5 phr of a dispersant (trade name: Emulsogen EPA 073, manufactured by Clariant) shown in Table 1 was added to the PHA aqueous suspension (solid content concentration: 52%), and then the solid content concentration was adjusted to 50%. . After the liquid was stirred for 30 minutes, sulfuric acid was added to adjust the pH to 4. The thermal stability of the PHA powder in the aqueous suspension was measured and/or evaluated by the methods described above. Table 2 shows the results.

[Comparative Example 3]
A PHA aqueous suspension with a solid content concentration of 52% was prepared by the same operation as in Example 1 up to the purification treatment. Next, 1 phr of a dispersant (trade name: Emulsogen EPA 073, manufactured by Clariant) shown in Table 1 was added to the PHA aqueous suspension (solid content concentration: 52%), and then the solid content concentration was adjusted to 50%. After the liquid was stirred for 30 minutes, sulfuric acid was added to adjust the pH to 4. The volume median diameter of PHA in the aqueous suspension and the thermal stability of the PHA powder were measured and/or evaluated by the methods described above. Table 2 shows the results.

[Reference Example 1]
A PHA aqueous suspension with a solid content concentration of 52% was prepared by the same operation as in Example 1 up to the purification treatment. Next, 1.5 phr of a dispersant (polyvinyl alcohol (PVA) manufactured by Kuraray Co., Ltd.) shown in Table 1 was added to the PHA aqueous suspension (solid content concentration 52%), and then the solid content concentration was adjusted to 50%. . After the liquid was stirred for 30 minutes, sulfuric acid was added to adjust the pH to 4. The volume median diameter of PHA in the aqueous suspension and the thermal stability of the PHA powder were measured and/or evaluated by the methods described above. Table 2 shows the results.

〔結果〕
表２および図１より、実施例では、比較例に比して、水性懸濁液中でのＰＨＡの凝集が抑制されることが示された。また、実施例では、ポリビニルアルコール（ＰＶＡ）を用いた場合（参考例）よりも、より少ない添加量でＰＨＡの凝集が抑制されることが分かった。

〔result〕
From Table 2 and FIG. 1, it was shown that aggregation of PHA in the aqueous suspension was suppressed in Examples compared to Comparative Examples. Moreover, in the examples, it was found that aggregation of PHA was suppressed with a smaller addition amount than in the case of using polyvinyl alcohol (PVA) (reference example).

Moreover, Table 2 and FIG. 2 show that the thermal stability of the PHA powder in Examples is superior to that in Comparative Examples.

From the above, it was found that according to the present production method, PHA (for example, PHA powder) can be produced with high productivity.

This production method can produce PHA (for example, PHA powder) with high productivity, and thus can be advantageously used in the production of PHA. In addition, the PHA powder and the like obtained by this production method can be suitably used in agriculture, fishery, forestry, gardening, medicine, hygiene products, clothing, non-clothing, packaging, automobiles, building materials, and other fields. .

Claims (5)

(a) preparing an aqueous suspension comprising a polyhydroxyalkanoic acid and a dispersant and having a pH of 7 or less; and (b) spray drying the aqueous suspension prepared in step (a). a process, including
the dispersant is composed of poly(ethylene oxide) (PEO) blocks and hydrophobic groups;
The PEO block in the dispersant has a repeating number of ethylene oxide (EO) of 20 or more ,
A method for producing polyhydroxyalkanoic acid, wherein the concentration of polyhydroxyalkanoic acid in the aqueous suspension prepared in step (a) is 65% by weight or less . The method for producing a polyhydroxyalkanoic acid according to claim 1, wherein the dispersant is a compound represented by the following formula (1).

(Wherein, R is a hydrocarbon group having 1 to 20 carbon atoms, and n is 20 to 60.) 3. The method for producing a polyhydroxyalkanoic acid according to claim 1, wherein the concentration of the polyhydroxyalkanoic acid in the aqueous suspension prepared in step (a) is 30% by weight or more . An aqueous suspension comprising a polyhydroxyalkanoic acid and a dispersant and having a pH of 7 or less, wherein the dispersant is composed of poly(ethylene oxide) (PEO) blocks and hydrophobic groups. ,
The aqueous suspension , wherein the PEO block in the dispersant has a repeating number of ethylene oxide (EO) of 20 or more . It contains a polyhydroxyalkanoic acid and a dispersing agent composed of poly(ethylene oxide) (PEO) blocks and hydrophobic groups, and has a bulk density of 0.30 to 0.70 kg/L and a median particle size is 80 to 200 μm ,
The polyhydroxyalkanoic acid powder, wherein the PEO block in the dispersant has a repeating number of ethylene oxide (EO) of 20 or more .

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