WO2021246373A1

WO2021246373A1 - Dispersion

Info

Publication number: WO2021246373A1
Application number: PCT/JP2021/020706
Authority: WO
Inventors: 忠川本; 敦史内山
Original assignee: 株式会社トレスバイオ研究所
Priority date: 2020-06-01
Filing date: 2021-05-31
Publication date: 2021-12-09
Also published as: JPWO2021246373A1; TW202210411A

Abstract

A dispersion is provided in which a water-insoluble powder, e.g., hydroxyapatite, is stably dispersed. The dispersion of a water-insoluble powder is characterized by containing a cellulose derivative.

Description

Dispersion

The present invention relates to a dispersion liquid in which a water-insoluble powder such as hydroxyapatite is dispersed.

Hydroxyapatite is a hydroxide of calcium and phosphoric acid, and is used as a biomaterial such as artificial bone and an oral composition material because of its high biocompatibility. In recent years, hydroxyapatite powder has been excellently adsorbed. Research and development are underway for various uses for adsorbing bacteria, proteins, lipids, etc. by utilizing their properties.

However, water-insoluble powders such as hydroxyapatite powder have poor dispersibility in liquids, and when they are attempted to be dispersed, precipitation and lumps occur, making it difficult to spray and apply using the dispersion liquid. For example, it has been difficult to apply hydroxyapatite powder when used for adsorption applications such as masks and air conditioner filters.
The present invention advantageously solves the above-mentioned problems, and an object of the present invention is to provide a dispersion liquid in which a water-insoluble powder is stably dispersed, which can be used for coating or spraying hydroxyapatite or other water-insoluble powder. And.

As a result of diligent studies, the present inventors can solve the above-mentioned problems by dispersing hydroxyapatite and a cellulose derivative, and by dispersing not only hydroxyapatite but also other water-insoluble powders with a cellulose derivative. We have found that the above problems can be solved, and have completed the present invention.

The present invention is as follows [1] to [12].
[1] A dispersion liquid of a water-insoluble powder, which comprises a cellulose derivative.
[2] The dispersion liquid of [1], wherein the water-insoluble powder is hydroxyapatite.
[3] The dispersion liquid of [1] or [2], which does not substantially precipitate a water-insoluble powder when centrifuged at 3600 rpm for 10 minutes.
[4] The dispersion liquid according to any one of [1] to [3], wherein the cellulose derivative is methyl cellulose or a salt thereof or carboxymethyl cellulose or a salt thereof.
[5] The dispersion liquid according to any one of [1] to [4], wherein the solvent is water.
[6] The dispersion liquid according to any one of [1] to [5], which contains 0.1% by mass or more of a water-insoluble powder.
[7] Further, the dispersion liquid according to any one of [1] to [6] containing an enzyme.
[8] Further, the dispersion liquid according to any one of [1] to [7], which contains an antibacterial agent.
[9] A paste composition containing a water-insoluble powder, a cellulose derivative and a polar solvent.
[10] A dispersion liquid of a water-insoluble powder, which comprises a step of mixing a water-insoluble powder, a cellulose derivative and a polar solvent to produce a paste composition, and a step of dispersing the paste composition in a polar solvent. Production method.
[11] A filter comprising a hydroxyapatite and a cellulose derivative.
[12] A mask characterized by carrying hydroxyapatite and a cellulose derivative.

According to the present invention, a water-insoluble powder such as hydroxyapatite can be stably and uniformly dispersed in a liquid.

It is a graph which showed the result of an example of the X-ray diffraction of a specific hydroxyapatite. It is a graph which showed the result of the X-ray diffraction of the crystalline hydroxyapatite. It is a graph which showed the result of the X-ray diffraction of the amorphous hydroxyapatite. It is a photograph of each dispersion liquid of Example and Comparative Example immediately after preparation. It is a photograph of each dispersion liquid of Example and Comparative Example after standing for 12 hours. It is a photograph of each dispersion liquid of an Example and a comparative example before centrifuging. It is a photograph of each dispersion liquid of an Example and a comparative example after being subjected to a centrifuge. It is a photograph of the dispersion liquid of the example after centrifuging.

The dispersion liquid of the present invention, a method for producing the same, a paste composition, a filter and a mask using the dispersion liquid will be described more specifically. The dispersion liquid of the present invention contains a water-insoluble powder such as hydroxyapatite powder and a cellulose derivative.

Hydroxyapatite powder has been attempted to be applied to various applications that require adsorptivity, but even if hydroxyapatite powder was added to water and stirred, it was not sufficiently dispersed. On the other hand, by dispersing the hydroxyapatite powder and the cellulose derivative, a stable dispersion of hydroxyapatite can be obtained. Hereinafter, unless otherwise specified, the water-insoluble powder will be described by taking hydroxyapatite as an example.

The lower limit of hydroxyapatite is not particularly defined in the dispersion liquid of the present invention, and may contain, for example, 0.1% by mass or more, preferably 2% by mass or more, more preferably 3% by mass or more, and more preferably. Can be contained in an amount of 5% by mass or more, more preferably 10% by mass or more. There has never been a technique for uniformly dispersing such high-concentration hydroxyapatite in water. Further, it has been confirmed that the dispersion liquid of the present invention can contain 40% by mass or 45% by mass without any particular upper limit of hydroxyapatite. Preferably, hydroxyapatite can be contained in an amount of 20% by mass or less. The dispersion liquid of the present invention is one in which hydroxyapatite is stably dispersed, and precipitation is unlikely to occur even if it is allowed to stand. Whether or not precipitation is unlikely to occur can be quickly confirmed by centrifuging. For example, the dispersion of the present invention has substantially no precipitation of hydroxyapatite after centrifugation at 3600 rpm for 10 minutes at room temperature, and substantially no precipitation of hydroxyapatite after being allowed to stand at room temperature for 12 hours. Those that do not occur are preferable. Here, the fact that hydroxyapatite precipitates do not substantially occur means that a white precipitate cannot be clearly confirmed by visual inspection.

The dispersion liquid in which hydroxyapatite is uniformly dispersed can adhere hydroxyapatite to any object, for example, non-woven fabric, filter, gauze, mask, wall, etc. by application. The coating method is not particularly limited, and examples thereof include spray coating, dipping, potting, roller coating, spin coating and the like. Since these coating methods can be applied uniformly, are simple and suitable for mass production, products to which hydroxyapatite is attached can be mass-produced at low cost. In addition, the mask and filter of the present invention can be expected to have the effect of reducing the amount of hydroxyapatite powder falling off.

Since hydroxyapatite powder has adsorptive properties, for example, by applying an aqueous dispersion of hydroxyapatite to a non-woven fabric or a mask and adhering hydroxyapatite to these objects, pollen, PM2.5, viruses, etc. are adsorbed. Can be expected.
Further, according to the dispersion liquid of the present invention, not only hydroxyapatite powder but also at least one powder selected from carbon powder, zinc powder and food material powder can be stably dispersed.

The components of the dispersion liquid of the present invention will be described more specifically.
(Water-insoluble powder)
The water-insoluble powder refers to a powder that is insoluble in water, and examples of the powder that can be stably dispersed by the technique of the present invention include hydroxyapatite, carbon powder, zinc powder, and food powder.
(Hydroxyapatite)
As hydroxyapatite, commercially available hydroxyapatite can be used. Commercially available hydroxyapatite includes those derived from minerals and those derived from living organisms, and any hydroxyapatite derived from minerals or living organisms can be used, but hydroxyapatite derived from living organisms is preferable. Organism-derived hydroxyapatite is hydroxyapatite obtained by using biological components (bone, coral, shell, eggshell, etc.) as a calcium source for obtaining hydroxyapatite. For hydroxyapatite, for example, a phosphoric acid solution is added to a calcium oxide solution (suspension) or a calcium hydroxide solution (suspension), or a calcium oxide solution (suspension) or calcium hydroxide is added to the phosphoric acid solution. It can be obtained by adding a solution (suspension). Hydroxyapatite derived from living organisms is, for example, calcined biological materials containing calcium such as bones, coral, shells, and eggshells to obtain calcium oxide or calcium hydroxide, which is used as an aqueous solution or a suspension. , Hydroxyapatite obtained by the addition of a phosphoric acid solution. Further, in the hydroxyapatite derived from living organisms, the crystallite size of the peak in which 2θ appears at 31.500 to 32.500 ° in X-ray structural analysis is 10 to 200 Å, preferably 30 to 150 Å, more preferably 50. Some are hydroxyapatite up to 120 Å (hereinafter, also referred to as "specific hydroxyapatite" for the sake of explanation). The crystallinity size represents the size of crystal grains and is a numerical value that serves as a guide for expressing crystallinity. The larger the value of the crystallinity size, the higher the crystallinity of the substance to be measured. Hydroxyapatite having a crystallite size in the above range is only uncrystallized (amorphous) hydroxyapatite or a mixture of amorphous hydroxyapatite and low degree of crystallization (low crystal type) hydroxyapatite. Means. Here, the "amorphous hydroxyapatite" in the present invention means a substance for which a chart as shown in FIG. 3 can be obtained by X-ray analysis. Further, the "low crystalline hydroxyapatite" in the present invention means that the chart obtained by X-ray analysis has a peak as compared with the chart obtained by X-ray analysis of crystalline hydroxyapatite (see, for example, the chart in FIG. 2). It is a substance with a relatively low degree of separation.
The crystallite size can be measured by, for example, an X-ray analyzer model number: RINT2200V / PC manufactured by Rigaku Co., Ltd.
The hydroxyapatite may contain hydroxyapatite or the like other than the above-mentioned specific hydroxyapatite.

Hydroxyapatite derived from eggshell has the trade name Bioapatite (trademark) of Bioapatite Co., Ltd. At present, the only specific hydroxyapatite available on the market is bioapatite, so the specific hydroxyapatite available on the market is presumed to be eggshell-derived apatite.

The average particle size of the hydroxyapatite used in the present invention is not particularly limited, but the average particle size is preferably 1 to 30 μm, more preferably 1 to 20 μm, and further preferably 1 to 10 μm. The average particle size can be measured by a laser light scattering diffraction method.

(Cellulose derivative)
The cellulose derivative of the present invention is cellulose or a compound in which cellulose is substituted or chemically modified, or a salt thereof. The degree of substitution of cellulose is not particularly limited. Examples of the cellulose derivative include cellulose, methyl cellulose, carboxymethyl cellulose and sodium carboxymethyl cellulose, and methyl cellulose or a salt thereof or carboxymethyl cellulose or a salt thereof (for example, sodium carboxymethyl cellulose) is preferable, and methyl cellulose is more preferable. Commercially available sodium carboxymethyl cellulose can be used as a thickener or the like. There are food additive grade and industrial grade, but any of them can be used depending on the use of the dispersion.

As the cellulose derivative, the particle size of the powder is not particularly limited, and a commercially available cellulose derivative can be used as it is.

The content of the cellulose derivative such as methyl cellulose and sodium carboxymethyl cellulose is 2% by mass or less, preferably 0.1 to 2% by mass in the dispersion liquid containing water. It is difficult to dissolve a content of more than 2% by mass in water. The lower limit is not particularly limited, but if the content is low, the effect of dispersing the hydroxyapatite powder in water is reduced.

(Polar solvent)
The polar solvent is a solvent containing a hydrogen atom bonded to oxygen (hydroxy group), nitrogen (amine) or the like, and is used when producing a paste composition containing hydroxyapatite and a cellulose derivative. It can also be used as a solvent for hydroxyapatite dispersion. Examples of the polar solvent include water, glycerin, polyethylene glycol, glycerol, alcohol (methanol, ethanol, butanol, propanol), formic acid, acetic acid or a mixture thereof. Further, a buffer such as PBS or PBST or an aqueous solution containing a component such as EDTA, DTT or mercaptoethanol can be used as the polar solvent.
The solvent of the hydroxyapatite dispersion and the polar solvent in the paste composition do not have to be the same. Water is preferable as the solvent for the hydroxyapatite dispersion. As the polar solvent of the paste composition, glycerin and polyethylene glycol are preferable.
When the enzyme is blended in the paste composition of the present invention, a commercially available enzyme solution may be used as it is, and a polar solvent may not be added separately. This is because a commercially available enzyme is stored in a polar solvent, and a paste composition can be produced by using this polar solvent.

The preferable mixing ratio of the polar solvent in the paste composition is 100 to 200 g of the organic liquid with respect to 10 g of hydroxyapatite.

(Other ingredients)
The dispersion of the present invention can contain functional components such as antibacterial components in addition to hydroxyapatite and cellulose derivatives. For example, by containing an antibacterial component, an antibacterial effect can be exerted by the action of the antibacterial component when the dispersion liquid is attached to a mask or a non-woven fabric. When the hydroxyapatite dispersion of the present invention contains an antibacterial component, it can be expected to have an effect equal to or higher than that of rubbing alcohol. This is because the disinfecting alcohol is volatile, so that the disinfecting effect is temporary, but the dispersion of the present invention can be expected to have a long-lasting antibacterial effect.

Examples of antibacterial components include copper, silver, cetylpyridinium chloride (CPC), isopropylmethylphenol (IPMP), lauroylsarcosine sodium (LSS), chlorhexidine hydrochloride (CHX), triclosan (TC), etc. contained in commercially available dentifrices. be. These antibacterial components do not reduce their antibacterial activity even when added to the dispersion of the present invention.

(Production method)
An example of the method for producing the dispersion liquid of the present invention will be described with the example of hydroxyapatite powder.
Hydroxyapatite powder, cellulose derivative powder, and polar solvent are mixed to obtain a paste composition. The manufacturing temperature may be normal temperature, and there is no need to heat or cool it.

A polar solvent such as water is added to the obtained paste composition to obtain an aqueous dispersion having a predetermined concentration of hydroxyapatite powder. In this case, it is not necessary to use the same polar solvent as the polar solvent used to obtain the paste composition. As the water, high-purity water, for example, reverse osmosis membrane water can be used, but tap water can also be used depending on the application.

When the antibacterial component is added, the hydroxyapatite powder may be added to the aqueous dispersion having a predetermined concentration, or the antibacterial component may be added at the time of the previous step.
According to the production method of the present invention, a dispersion containing a high concentration of hydroxyapatite can be produced with high efficiency and low cost.

(Use)
The dispersion liquid of the present invention can be applied to non-woven fabrics, gauze, masks, filters, walls and the like. The coating method is not particularly limited, and examples thereof include spray coating, dipping, potting, roller coating, spin coating and the like. Nonwoven fabric, gauze, etc. coated with a dispersion liquid can be processed into a mask, and can also be used as a filter for an air conditioner or the like. For example, in the use of masks, the adsorption effect of hydroxyapatite can be expected to adsorb pollen, PM2.5, viruses and the like. In addition to adsorbing pollen, PM2.5, viruses, etc., it can also be expected to have a deodorizing function in the use of filters such as air conditioners.
Further, when the dispersion liquid of the present invention contains an antibacterial component, an antibacterial effect can be expected.

The application of the dispersion liquid of the present invention is not limited to the above-mentioned masks and filters, but can be applied to a wide range of applications such as air purification, and has great industrial applicability.

Hereinafter, the contents of the present disclosure will be described in more detail by way of examples. It goes without saying that the scope of the present disclosure is not limited by the examples.

Hydroxyapatite (trade name: hydroxyapatite manufactured by Wako Pure Chemical Industries, Ltd.) commercially available as hydroxyapatite, and bioapatite (hereinafter, "egguapatite"), which is a hydroxyapatite derived from eggshell as the specific hydroxyapatite described above. I prepared.). In addition, sodium carboxymethyl cellulose of Wako Pure Chemical Industries, Ltd. was prepared. Furthermore, glycerin was prepared as a polar solvent.

10 g of hydroxyapatite and 0.1 g of sodium carboxymethyl cellulose were mixed. This mixture was added to 10 g of glycerin and stirred to obtain a paste composition.
^{50 cm 3} of water was added to the obtained paste composition and stirred to obtain an aqueous dispersion (hereinafter, the hydroxyapatite dispersion is referred to as "Example").

When the obtained hydroxyapatite aqueous dispersion of the example was allowed to stand at room temperature for 24 hours, no precipitation of hydroxyapatite occurred. The photographs are shown in FIGS. 4 and 5. The right side of FIGS. 4 and 5 is an example, and hydroxyapatite is an example of hydroxyapatite derived from eggshell, that is, the trade name bioapatite of Bioapatite Co., Ltd., and the left side of FIGS. 4 and 5 is a comparative example. Further, FIG. 4 is a photograph immediately after preparing the dispersion, and FIG. 5 is a photograph after allowing it to stand at room temperature. As is clear from FIGS. 4 and 5, precipitation did not occur in the examples even after standing, and a stable and dispersed state was maintained. Further, when observed after centrifuging at 3600 rpm for 10 minutes, no precipitation of hydroxyapatite occurred. The photographs are shown in FIGS. 6 and 7. FIG. 6 is a photograph before centrifugation and FIG. 7 is a photograph after centrifugation. Further, the right side of FIGS. 6 and 7 is an example. As is clear from FIGS. 6 and 7, no precipitation is substantially formed in the examples even after centrifugation. Although not shown in FIGS. 4 and 5, examples in which hydroxyapatite is commercially available hydroxyapatite, that is, trade name: hydroxyapatite manufactured by Wako Pure Chemical Industries, Ltd., were also allowed to stand immediately after preparation of the dispersion and at room temperature. No precipitation occurred later, and a stable and dispersed state was maintained. Further, when observed after centrifuging at 3600 rpm for 10 minutes, no precipitation of hydroxyapatite occurred.

Further, when the obtained hydroxyapatite aqueous dispersion and egguapatite aqueous dispersion to which cetylpyridinium chloride (CPC) was added as an antibacterial component were left for 10 days, hydroxyapatite precipitation did not occur in any of them. rice field. Further, when observed after being subjected to a centrifuge at 3600 rpm, no precipitation of hydroxyapatite occurred.

As a comparative example, when 50 cm ³ of water was added to 10 g of hydroxyapatite and stirred, hydroxyapatite was precipitated shortly after the completion of stirring. The photographs are shown in FIGS. 4 and 5. The left side of FIGS. 4 and 5 is a comparative example. As is clear from FIGS. 4 and 5, precipitation occurs in the comparative example. Further, photographs of a comparative example when subjected to a centrifuge are shown in FIGS. 6 and 7. The left side of FIGS. 6 and 7 is an example. As is clear from FIGS. 6 and 7, precipitation occurs in the comparative example after being centrifuged.
Further, when 50 cm ³ of water was added to 10 g of egguapatite and stirred, hydroxyapatite was precipitated immediately after the stirring was completed.

A commercially available hydroxyapatite (trade name: hydroxyapatite manufactured by Wako Pure Chemical Industries, Ltd.) was prepared as hydroxyapatite. In addition, commercially available methyl cellulose (trade name Metrose manufactured by Shinetsu Cellulose Co., Ltd.) was prepared. Furthermore, glycerin was prepared as a polar solvent.

10 g of the above hydroxyapatite and 0.1 g of the above methylcellulose were mixed. This mixture was added to 10 g of glycerin and stirred to obtain a paste composition.
^{50 cm 3} of water was added to the obtained paste composition and stirred to obtain an aqueous dispersion.

When the obtained hydroxyapatite aqueous dispersion was allowed to stand at room temperature for 24 hours, no precipitation of hydroxyapatite occurred. Further, when observed after centrifuging at 3600 rpm for 10 minutes, no precipitation of hydroxyapatite occurred. A photograph of the dispersion liquid after being centrifuged is shown in FIG. As is clear from FIG. 8, no precipitation was substantially formed even after the centrifugation.

Further, when the obtained hydroxyapatite aqueous dispersion to which cetylpyridinium chloride (CPC) was added as an antibacterial component was left for 10 days, no precipitation of hydroxyapatite occurred. Further, when observed after centrifuging at 3600 rpm, no precipitation of hydroxyapatite occurred.

A commercially available hydroxyapatite (trade name: hydroxyapatite manufactured by Wako Pure Chemical Industries, Ltd.) was prepared as hydroxyapatite. In addition, commercially available methyl cellulose (trade name Metrose manufactured by Shinetsu Cellulose Co., Ltd.) was prepared.

40 g of the above hydroxyapatite and 2.0 g of the above methylcellulose were mixed. Then, 10 g of glycerin was added and stirred to obtain a paste composition. Further, 50 cm ³ of water was added and stirred to obtain an aqueous dispersion.
As another example, 45 g of the above hydroxyapatite and 2.0 g of the above methylcellulose were mixed. Then, 10 g of glycerin was added and stirred to obtain a paste composition. Further, 45 cm ³ of water was added and stirred to obtain an aqueous dispersion.

When each of the obtained hydroxyapatite aqueous dispersions was allowed to stand at room temperature for 24 hours, no precipitation of hydroxyapatite occurred. Further, when observed after centrifuging at 3600 rpm for 10 minutes, no precipitation of hydroxyapatite occurred. Twice

As a comparative example, when a commercially available hydroxyapatite-containing liquid as a coating agent for masks was examined, it was found that the composition contained hydroxyapatite, ethanol, water, and essential oil, and hydroxyapatite was precipitated in the liquid. rice field. This mask coating agent is used to shake the container containing the hydroxyapatite-containing liquid each time it is used, which requires the troublesome work of shaking before applying to the mask, and if the shaking method is not sufficient, the mask will be used. The coating agent could not be applied evenly.

Claims

A dispersion of water-insoluble powder characterized by containing a cellulose derivative.
The dispersion liquid according to claim 1, wherein the water-insoluble powder is hydroxyapatite.
The dispersion liquid according to claim 2, wherein the water-insoluble powder does not substantially precipitate when centrifuged at 3600 rpm for 10 minutes.
The dispersion liquid according to any one of claims 1 to 3, wherein the cellulose derivative is methyl cellulose or a salt thereof or carboxymethyl cellulose or a salt thereof.
The dispersion liquid according to any one of claims 1 to 4, wherein the solvent is water.
The dispersion liquid according to any one of claims 1 to 5, which contains 0.1% by mass or more of water-insoluble powder.
Further, the dispersion liquid according to any one of claims 1 to 6, which contains an enzyme.
Further, the dispersion liquid according to any one of claims 1 to 7, which contains an antibacterial agent.
A paste composition containing a water-insoluble powder, a cellulose derivative and a polar solvent.
A method for producing a dispersion liquid of a water-insoluble powder, which comprises a step of mixing a water-insoluble powder, a cellulose derivative and a polar solvent to produce a paste composition, and a step of dispersing the paste composition in a polar solvent.
A filter characterized by supporting hydroxyapatite and a cellulose derivative.
A mask characterized by carrying hydroxyapatite and a cellulose derivative.