Particles and method of manufacturing same

Abstract

To provide novel particles that, when added to a preparation, allow properties such as hardness and collapsibility to be easily controlled.SOLUTION: Particles having a maximum size of 1-800 nm are obtained from a cell wall component.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to particles having a maximum diameter of 1 to 800 nm obtained from components constituting a cell wall, which are excellent in characteristics such as thermal stability. nm and having a maximum diameter of 1 to 800 nm obtained from components constituting the cell wall, which are excellent in characteristics such as thermal stability.

Background Art

[0002] So far, a large number of fine particles have been used in various fields. Such fine particles include, for example, nanoparticles such as fullerenes and carbon nanotubes, and fine particles derived from natural products such as liposomes. The former has physical properties such as heat resistance and solvent resistance, and the latter has a variety of physical properties such as being derived from natural products and being easily applicable to the human body.

[0003] However, in each technical field, the physical properties of such fine particles are expected to be further improved at present. In addition, the finer and more nano-sized the fine particles are, the more difficult they are to manufacture, and improvement in their quality stability and productivity is also desired. Among the technical fields using such fine particles, the present inventors focused on the technical field of pharmaceuticals. That is, in the technical field of pharmaceuticals, almost all pharmaceuticals are added with additives such as excipients, stabilizers, preservatives, and molding aids for the purposes of facilitating formulation, stabilizing quality, and enhancing utility (see Patent Document 1). However, when an additive for increasing the hardness of a pharmaceutical is used, although the hardness of the pharmaceutical increases, there is a tendency for the disintegrability to decrease. On the contrary, when importance is attached to the disintegrability of a pharmaceutical, there is a tendency for the problem that the desired hardness cannot be obtained to occur.

[0004]

[0005] Among the preparations, over-the-counter drugs that do not require a doctor's prescription are strictly controlled by medical institutions. Unlike prescription drugs, they are displayed in pharmacies and can be easily purchased by the general public. However, depending on the store configuration, the temperature inside the pharmacy may not be constant, so Medicines tend to be required to have higher heat and cold resistance than medical drugs. Similarly, there is a trend for cosmetics and the like to be required to have higher heat and cold resistance. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Patent Publication 2015-193600 Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention has been made in consideration of such circumstances, and is a method for improving hardness and disintegration properties by adding the compound to a pharmaceutical preparation. The properties such as heat resistance, etc. can be easily controlled without impairing these properties. It is possible to improve cold resistance, and even if it is mixed with over-the-counter medicines, it will be able to fully demonstrate its properties. This provides new fine particles that can [Means for solving the problem]

[0008] The present invention is directed to a particle having a maximum diameter of 1 to 800 nm obtained from a component constituting a cell wall. The gist of the report is as follows.

[0009] In addition, among the particles of the first aspect, the particles obtained from the components constituting the cell wall are spherical. The second aspect is that the particles of the first or second aspect are made of components constituting the cell wall. The third aspect is that the particles obtained from the above process are mainly composed of sugar.

[0010] Furthermore, a method for producing particles according to any one of the first to third aspects, comprising a step of lysing a cell wall and a step of separating particles from the lysate obtained by the step, is defined as the fourth aspect, and a method for producing particles according to any one of the first to third aspects, comprising a step of preparing a liquid containing a component constituting a cell wall and a step of separating particles from the liquid, is defined as the fifth aspect. And a composition containing particles according to any one of the first to third aspects is defined as the sixth aspect, and among the compositions according to the sixth aspect, a composition that is at least one selected from the group consisting of a pharmaceutical composition, a food composition, and a cosmetic composition is defined as the seventh aspect.

[0011] That is, the present inventors have conducted various studies to obtain fine particles applicable to various uses. As a result, they have found new fine microparticles that have not been clarified so far. These fine particles have been clarified to be excellent in dispersibility, heat resistance, cold resistance, etc. by previous studies.

[0012]

Advantages of the Invention

[0013] Thus, since the particles of the present invention are obtained from components constituting a cell wall, they can enjoy the health benefits derived from natural dietary fiber. Moreover, the maximum diameter is extremely small, ranging from 1 to 800 nm, and it has solubility resistance in both aqueous and oil-based systems, and is excellent in heat resistance, cold resistance, dryness resistance, etc., so it can be incorporated into a wide range of formulations. In addition, when the particles of the present invention are used in a formulation, it is possible to easily control characteristics such as hardness and disintegration property, and obtain a formulation having desired characteristics. ​​​​​​​​​​​​​​

[0014] Among them, since the particles obtained from the components constituting the cell wall are spherical, they have excellent fluidity and dispersibility.

[0015] And since the particles obtained from the components constituting the cell wall mainly contain sugar, the protein content that is likely to become an allergen is low or completely absent, so it can be made safer for clothing use.

[0016] Furthermore, a method for producing the particles of the present invention, which comprises a step of lysing the cell wall and a step of separating the particles from the lysate obtained by this step, can use the components constituting the desired cell wall by selecting an organism having a cell wall, and can increase the degree of freedom of the particle design obtained.

[0017] Also, a method for producing the particles of the present invention, which comprises preparing a liquid containing the components constituting the cell wall and a step of separating the particles from the liquid, can exclude impurities other than the components constituting the cell wall in advance, so that the particles can be produced efficiently.

[0018] And the composition containing the particles of the present invention can enjoy the health benefits derived from natural dietary fiber.

[0019] Also, when the composition is at least one selected from the group consisting of a pharmaceutical composition, a food composition, and a cosmetic composition, since the particles of the present invention have a low or no protein content that is likely to become an allergen, the safety can be further enhanced.

[0020] ​​​​​​​​​​​In the present invention, the "main component" means a component that affects the properties of the material, and the content of that component is usually 50% by weight or more of the entire material.

Brief Description of the Drawings

[0021]

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Embodiments for Carrying Out the Invention

[0022] Next, embodiments for carrying out the present invention will be described. However, the present invention is not limited to this embodiment. form.

[0023] In the present invention, the "component constituting the cell wall" refers to a substance that forms a cell wall found in cells of organisms belonging to the plant kingdom, organisms belonging to the fungal kingdom, organisms belonging to the protist kingdom, organisms belonging to the prokaryote kingdom, etc., and means including the saccharides constituting this substance. As organisms belonging to the above-mentioned plant kingdom, for example, red algae, brown algae, green algae, charophytes, moss plants, fern plants, seed plants, etc. can be mentioned. Also, as organisms belonging to the above-mentioned fungal kingdom, for example, phycomycetes, ascomycetes, basidiomycetes, lichens, etc. can be mentioned, and as organisms belonging to the protist kingdom, for example,

[0024] diatoms can be mentioned. Furthermore, as organisms belonging to the prokaryote kingdom, for example, bacteria can be mentioned. As organisms belonging to the above-mentioned fungal kingdom, for example, phycomycetes, ascomycetes, basidiomycetes, lichens, etc. can be mentioned, and as organisms belonging to the protist kingdom, for example, For example, bacteria, cyanobacteria, etc. can be mentioned. Among these, those with high uniformity are mass-produced easily. From the viewpoint of being easy to mass-produce, organisms belonging to the fungal kingdom, protist kingdom, and prokaryote kingdom, and so-called algae (red algae, brown algae, green algae, charophytes, diatoms, cyanobacteria, etc.) are preferably used as materials and, among the fungal kingdom in particular, yeasts belonging to the ascomycetes, basidiomycetes, etc. are preferably used . Also, from the viewpoint that the obtained particles exhibit a more excellent effect as an additive for a preparation, among seed plants, those belonging to the legume family and ginger family, among green algae, those belonging to the Chlorellaceae family, among ascomycetes, basidiomycetes, etc., yeasts belonging to the genus Saccharomyces or Schizosaccharomyces are preferably used.

[0025] Note that the components constituting the cell wall vary greatly in composition and their blending depending on the organism. Therefore, the ratio of the constituent sugars of the particles varies depending on the organism used as the material. For example , the cell wall of organisms belonging to the plant kingdom usually has a two-layer structure, and cellulose, lignin , hemicellulose are cited as typical components. And among organisms belonging to the plant kingdom too, the content ratio of hemicellulose varies greatly depending on the species. Also, among algae there are some that do not have lignin, which is a secondary cell.

[0026] Furthermore, the cell wall of yeast usually has a single layer, and β-glucan, galactomannan are cited as typical components. Also, the cell wall of lactic acid bacteria classified as bacteria usually has a single layer, and dextran, teichoic acid, cell wall polysaccharide are cited as typical components .

[0027] That is, the fact that the particles of the present invention are obtained from the components constituting the cell wall means that the material It can be inferred that the ratio of the constituent sugars of the obtained particles is determined for each type of organism used as the material. For example, since licorice (scientific name: Glycyrrhiza uralensis) is a seed plant, its cell wall contains a large amount of cellulose, lignin, and hemicellulose. Usually, the constituent sugars are approximately 60% by weight of glucose, 10 - 30% by weight of lignin, and 10 - 30% by weight of others. On the other hand, as shown in Example 1 (Tables 1 and 2) described later, the particles of the present invention using licorice as the material contain 64.8% by weight of glucose as the constituent sugar, have a small content of other sugars but have many types, and contain 14.0% by weight of lignin. Thus, the cell wall of licorice and the particles of the present invention using licorice as the material have extremely similar ratios of constituent sugars and lignin. It should be noted that the following component compositions are all shown on a weight basis (parts by weight, % by weight) unless otherwise specified.

[0028] In addition, since chlorella belongs to green algae, like licorice, its cell wall contains a large amount of cellulose, lignin, and hemicellulose. And as shown in Example 3 (Tables 3 and 4) described later, the particles of the present invention using chlorella as the material contain 59.8% by weight of glucose as the constituent sugar, have a small content of other sugars but have many types, and contain 6.1% by weight of lignin. The reason why the lignin content of chlorella is lower than that of licorice is considered to be due to the fact that lignin is a typical component that appeared last in the process of plant evolution and is based on the species difference between chlorella and licorice.

[0029] Furthermore, yeast usually belongs to ascomycetes or basidiomycetes, etc., and its cell wall is β- ​​It contains a large amount of glucan and galactomannan, while containing almost no lignin. This To reflect this, the particles of the present invention using yeast as a material are shown in Example 4 (Tables 5 and 6) described later As shown, almost all of the constituent sugars are glucose, and except for having 0.6% by weight of lignin , it has almost no sugars other than glucose.

[0030] The particles of the present invention may be obtained from such components constituting the cell wall, and it is not necessary to specify these components. However, if such components constituting the cell wall are specifically mentioned, for example, cellulose, hemicellulose, pectin, glycoprotein, phenol ol compounds and the like.

[0031] Examples of the above hemicellulose include xyloglucan, 1,3-1,4-β-D-glu lucan, xylan, glucomannan, carlose and the like. Examples of the above pectin include homogalacturonan, rhamnogalacturonan I, rhamnogalacturonan II, api ogalacturonan, arabinogalactan, arabinan, galactan and the like. Examples of the above glycoprotein include extensin, arabinogalactan protein and the like. Examples of the above phenol compound include lignin and the like.

[0032] Among the components constituting the above cell wall, many have a structure in which a plurality of sugars are bonded. Examples of such constituent sugars include glucose, xylose, galactose, fucose, cello triose, cellotetraose, xylan, arabinose, mannose, rhamnose and the like. These sugars are also included in the components constituting the above cell wall.

[0033] In the present invention, the "particle" means a substance whose structure appears to be a two-layer structure, bilayer structure, multilayer structure, or multiple bilayer structure when observed with an electron microscope. That is, the particles of the present invention have different electron densities at least between the outermost layer and the interior.

[0034] The particles of the present invention have a maximum diameter of 1 to 800 nm, more preferably 10 to 800 nm, even more preferably 30 to 500 nm, and even more preferably 40 to 300 nm. In the present invention, the "maximum diameter of the particle" refers to the diameter when the particle is spherical, and the maximum length when the particle has other shapes. The diameter of the particle can be measured, for example, by dispersing the obtained particles in ultrapure water and measuring the dispersion using a thick-suspension particle size analyzer. When measuring the particle diameter using a thick-suspension particle size analyzer, the calculated average particle diameter is taken as the maximum diameter of the particle, and it is sufficient if the calculated average particle diameter falls within the range defined by the maximum diameter.

[0035] The particles of the present invention usually have a shape without sharp parts such as carbon nanotubes, and preferably have a spherical shape. The above-mentioned sphere includes not only a perfect sphere but also shapes such as an ellipsoid. The shape of the particle can be determined, for example, by photographing negatively stained particles with a transmission electron microscope and observing their appearance. For example, particles aggregated in a pellet form are dispersed in ultrapure water, this dispersion is adsorbed onto a mesh, and a staining solution is placed thereon. Then, the excess staining solution is blotted with filter paper and dried, and the appearance of the particles can be observed by photographing with a transmission electron microscope.

[0036] The particles of the present invention have good dispersibility in both aqueous and oil-based liquids, and particularly high dispersibility in aqueous liquids. Moreover, their excellent dispersibility is maintained for a long period of time. The dispersibility of the particles can be determined, for example, by dispersing the obtained particles in ultrapure water, photographing the dispersion with a transmission electron microscope, and observing the degree of dispersion. Also, the degree of retention of dispersibility can be determined by comparing the above dispersion with that after being stored for a certain period of time. The particles of the present invention are excellent in pressure resistance and heat resistance, and there is almost no change in particle size even under pressurization up to at least 2 atmospheres and heating up to 121°C. The pressure resistance and heat resistance of the particles can be determined, for example, by calculating the particle size distribution of the particles dispersed in ultrapure water and those in the dispersion after pressurization and heating using a concentrated system particle size analyzer, and comparing the two. When the particle size distributions in both do not vary, it can be determined. For the particles of the present invention, the dispersion is carried out in ultrapure water, and the dispersion liquid is photographed with a transmission electron microscope. The degree of dispersion can be determined by observing it. Also, by comparing the above dispersion liquid with that after being stored for a certain period of time, the degree of retention of dispersibility can be determined.

[0037] The particles of the present invention are excellent in cold resistance and dryness resistance, and there is almost no change in particle size even after cooling from -50 to -80°C and drying. The cold resistance and dryness resistance of the particles can be determined, for example, by calculating the particle size distribution of the particles dispersed in ultrapure water and those in the dispersion obtained by freeze-drying the dispersion liquid (-50°C) and then redispersing the dried product in ultrapure water using a concentrated system particle size analyzer, and comparing the two. When the particle size distributions in both do not vary, it can be determined. Also, even when the particles contained in the product obtained by dispersing the above freeze-dried product in ultrapure water after storing it at -80°C for 7 days are similarly compared, there is no variation in the particle size distribution. In addition, even when pressurization, heating, cooling, and drying are carried out, the structure of the particles of the present invention does not change. For the particles dispersed in ultrapure water and those in the dispersion obtained by pressurizing and heating this dispersion liquid, the particle size distribution of each is calculated using a concentrated system particle size analyzer. When the two are compared, it can be determined that the particle size distribution does not vary in both.

[0038] The particles of the present invention are excellent in cold resistance and dryness resistance, and there is almost no change in particle size even after cooling from -50 to -80°C and drying. The cold resistance and dryness resistance of the particles can be determined, for example, as follows: For the particles dispersed in ultrapure water and those in the dispersion obtained by freeze-drying this dispersion liquid (-50°C) and then redispersing the dried product in ultrapure water, the particle size distribution of each is calculated using a concentrated system particle size analyzer. When the two are compared, it can be determined that the particle size distribution does not vary. Also, for the particles contained in the product obtained by dispersing the above freeze-dried product in ultrapure water after storing it at -80°C for 7 days, when compared in the same way, there is no variation in the particle size distribution.

[0039] Note that even when pressurization, heating, cooling, and drying are performed, the structure of the particles of the present invention does not change.​​​​​ It can be discriminated by observing the structures of the particles contained therein with an electron microscope for a dispersion obtained by dispersing particles in ultrapure water, a dispersion obtained by pressurizing and heating this dispersion, or a dispersion obtained by redispersing a cooled and dried product in ultrapure water again. These are characteristics that cannot be obtained with conventional nanoparticles such as liposomes. Such particles can be produced, for example, by a method comprising a step of lysing a cell wall and a step of separating particles from the lysate obtained by this step.

[0040] As the above step of lysing the cell wall, for example, heat treatment, ultrasonic treatment, treatment with a degrading enzyme, alkaline degradation treatment, etc. can be mentioned. These can be used alone or in combination. Among them, from the viewpoints of efficiency and consideration for health, heat treatment and treatment with a degrading enzyme are preferable, and heat treatment is particularly preferable. As the above heat treatment, for example, an organism having a cell wall is immersed in a liquid, and this liquid together with this organism is heated to dissolve the components constituting the cell wall in the liquid to obtain a lysate. More specifically, first, an organism having a cell wall as a material is prepared. This organism may be in any state, but from the viewpoint of efficiency, it is preferably dried and pulverized. The prepared organism is immersed in a separately prepared liquid and usually heated at 60°C or higher for 3 minutes or more to obtain a lysate. However, if the prepared organism is one that has been heated and dried while immersed in the liquid, it may not be necessary to further heat it when immersed in the liquid. However, since the yield tends to increase as the heating time is longer, heating may be performed. The above liquid and

[0041] As the above step of lysing the cell wall, for example, heat treatment, ultrasonic treatment, treatment with a degrading enzyme, alkaline degradation treatment, etc. can be mentioned. These can be used alone or in combination. Among them, from the viewpoints of efficiency and consideration for health, heat treatment and treatment with a degrading enzyme are preferable, and heat treatment is particularly preferable. As the above heat treatment, for example, an organism having a cell wall is immersed in a liquid, and this liquid together with this organism is heated to dissolve the components constituting the cell wall in the liquid to obtain a lysate. More specifically, first, an organism having a cell wall as a material is prepared. This organism may be in any state, but from the viewpoint of efficiency, it is preferably dried and pulverized. The prepared organism is immersed in a separately prepared liquid and usually heated at 60°C or higher for 3 minutes or more to obtain a lysate. However, if the prepared organism is one that has been heated and dried while immersed in the liquid, it may not be necessary to further heat it when immersed in the liquid. However, since the yield tends to increase as the heating time is longer, heating may be performed. The above liquid and As the above heat treatment, for example, an organism having a cell wall is immersed in a liquid, and this liquid together with this organism is heated to dissolve the components constituting the cell wall in the liquid to obtain a lysate.

[0042] As the above heat treatment, for example, an organism having a cell wall is immersed in a liquid, and this liquid together with this organism is heated to dissolve the components constituting the cell wall in the liquid to obtain a lysate. More specifically, first, an organism having a cell wall as a material is prepared. This organism may be in any state, but from the viewpoint of efficiency, it is preferably dried and pulverized. The prepared organism is immersed in a separately prepared liquid and usually heated at 60°C or higher for 3 minutes or more to obtain a lysate. However, if the prepared organism is one that has been heated and dried while immersed in the liquid, it may not be necessary to further heat it when immersed in the liquid. However, since the yield tends to increase as the heating time is longer, heating may be performed. The above liquid and As the above heat treatment, for example, an organism having a cell wall is immersed in a liquid, and this liquid together with this organism is heated to dissolve the components constituting the cell wall in the liquid to obtain a lysate. More specifically, first, an organism having a cell wall as a material is prepared. This organism may be in any state, but from the viewpoint of efficiency, it is preferably dried and pulverized. The prepared organism is immersed in a separately prepared liquid and usually heated at 60°C or higher for 3 minutes or more to obtain a lysate. However, if the prepared organism is one that has been heated and dried while immersed in the liquid, it may not be necessary to further heat it when immersed in the liquid. However, since the yield tends to increase as the heating time is longer, heating may be performed. The above liquid and As the above heat treatment, for example, an organism having a cell wall is immersed in a liquid, and this liquid together with this organism is heated to dissolve the components constituting the cell wall in the liquid to obtain a lysate. More specifically, first, an organism having a cell wall as a material is prepared. This organism may be in any state, but from the viewpoint of efficiency, it is preferably dried and pulverized. The prepared organism is immersed in a separately prepared liquid and usually heated at 60°C or higher for 3 minutes or more to obtain a lysate. However, if the prepared organism is one that has been heated and dried while immersed in the liquid, it may not be necessary to further heat it when immersed in the liquid. However, since the yield tends to increase as the heating time is longer, heating may be performed. The above liquid and As the above heat treatment, for example, an organism having a cell wall is immersed in a liquid, and this liquid together with this organism is heated to dissolve the components constituting the cell wall in the liquid to obtain a lysate. More specifically, first, an organism having a cell wall as a material is prepared. This organism may be in any state, but from the viewpoint of efficiency, it is preferably dried and pulverized. The prepared organism is immersed in a separately prepared liquid and usually heated at 60°C or higher for 3 minutes or more to obtain a lysate. However, if the prepared organism is one that has been heated and dried while immersed in the liquid, it may not be necessary to further heat it when immersed in the liquid. However, since the yield tends to increase as the heating time is longer, heating may be performed. The above liquid and A liquid used as various solvents such as water and alcohol may be used alone or in a mixture of two or more. However, considering the ingestion of particles, etc., from the perspective of health considerations, water or an aqueous liquid is preferably used.

[0043] In the present invention, "dissolving a component constituting the cell wall in a liquid" means disrupting the structure of the cell wall by separating the basic skeleton and the substrate, etc., and forming a system in which the component is dispersed in the liquid. This also includes the meaning of dispersing in the liquid by decomposing a polysaccharide, which is one of the components, into smaller sizes.

[0044] Next, as a step of separating the particles of the present invention from the lysate obtained by the above step, for example, centrifugation, filter filtration, ultrafiltration, ultracentrifugation, etc. can be mentioned. These are more suitably used according to the type of organism having the cell wall as the material, etc. Among them, from the viewpoint of ease of operation, centrifugation and filter filtration are preferable, and from the viewpoint of enhancing the purification degree, it is preferable to use these in combination.

[0045] Regarding the above centrifugation, although it depends on the size of the particles, for example, a method of centrifuging the lysate at 10,000 to 1,000,000 G and collecting the supernatant can be mentioned (coarse separation step). Further, in order to enhance the purification degree, for example, the above supernatant may be filtered through a filter with a pore size of 0.22 to 0.45 μm to obtain the filtrate (precision separation step).

[0046] Thus, the particles of the present invention are for the purpose of performing substitution of terminal molecules, etc. on components constituting the cell wall, such as cellulose, etc. (for example, a method using caustic soda, hydrochloric acid, etc.) (for example, a method using caustic soda, hydrochloric acid, etc.) Since is not adopted, it is also excellent in safety.

[0047] In the above production example, an organism having a cell wall is used as a material. However, instead of an organism, cellulose, hemicellulose, pectin, glucan, pullulan, glycoprotein, phenolic compounds, etc., which are specific components constituting the cell wall, may be used as a material. Among them, pectin and glucan are preferable. That is, at least one of the above specific components constituting the cell wall is dissolved in a liquid to prepare a liquid containing the components constituting the cell wall, and the particles of the present invention may be separated from the above liquid. According to this, since impurities derived from organisms other than the components constituting the cell wall can be excluded in advance, particles can be efficiently produced. Cellulose, hemicellulose, pectin, glucan, pullulan, glycoprotein, phenolic Compounds and other specific components constituting the cell wall may be used as materials, and pectin and glucan are particularly preferable. That is, among the above specific components constituting the cell wall, at least One component is dissolved in a liquid to prepare a liquid containing the components constituting the cell wall, and the particles of the present invention may be separated from the above liquid. According to this, impurities derived from organisms other than the components constituting the cell wall can be excluded in advance, so that particles can be efficiently produced. According to this, impurities derived from organisms other than the components constituting the cell wall can be excluded in advance, so that particles can be efficiently produced. According to this, impurities derived from organisms other than the components constituting the cell wall can be excluded in advance, so that particles can be efficiently produced. According to this, impurities derived from organisms other than the components constituting the cell wall can be excluded in advance, so that particles can be efficiently produced.

[0048] The particles of the present invention can be used as additives to control various properties such as hardness and disintegrability by being incorporated into formulations such as pharmaceuticals, foods, and cosmetics. When considering additives in a formulation, it is important that the additives do not limit the amount of the main ingredient. However, since the particles of the present invention can control each property with a relatively small amount of addition to the composition constituting the formulation, they do not limit the amount of the main ingredient and can increase the degree of freedom in formulation. The particles of the present invention can be used as additives to control various properties such as hardness and disintegrability by being incorporated into formulations such as pharmaceuticals, foods, and cosmetics. When considering additives in a formulation, it is important that the additives do not limit the amount of the main ingredient. However, since the particles of the present invention can control each property with a relatively small amount of addition to the composition constituting the formulation, they do not limit the amount of the main ingredient and can increase the degree of freedom in formulation. The particles of the present invention can be used as additives to control various properties such as hardness and disintegrability by being incorporated into formulations such as pharmaceuticals, foods, and cosmetics. When considering additives in a formulation, it is important that the additives do not limit the amount of the main ingredient. However, since the particles of the present invention can control each property with a relatively small amount of addition to the composition constituting the formulation, they do not limit the amount of the main ingredient and can increase the degree of freedom in formulation. The particles of the present invention can be used as additives to control various properties such as hardness and disintegrability by being incorporated into formulations such as pharmaceuticals, foods, and cosmetics. When considering additives in a formulation, it is important that the additives do not limit the amount of the main ingredient. However, since the particles of the present invention can control each property with a relatively small amount of addition to the composition constituting the formulation, they do not limit the amount of the main ingredient and can increase the degree of freedom in formulation. The particles of the present invention can be used as additives to control various properties such as hardness and disintegrability by being incorporated into formulations such as pharmaceuticals, foods, and cosmetics. When considering additives in a formulation, it is important that the additives do not limit the amount of the main ingredient. However, since the particles of the present invention can control each property with a relatively small amount of addition to the composition constituting the formulation, they do not limit the amount of the main ingredient and can increase the degree of freedom in formulation. The particles of the present invention can be used as additives to control various properties such as hardness and disintegrability by being incorporated into formulations such as pharmaceuticals, foods, and cosmetics. When considering additives in a formulation, it is important that the additives do not limit the amount of the main ingredient. However, since the particles of the present invention can control each property with a relatively small amount of addition to the composition constituting the formulation, they do not limit the amount of the main ingredient and can increase the degree of freedom in formulation.

[0049] When the particles of the present invention are incorporated into a formulation, it is preferably contained in an amount of 0.01 to 95% by weight, more preferably 0.01 to 90% by weight, still more preferably 0.1 to 50% by weight, and even more preferably 1 to 20% by weight based on the total composition constituting the formulation. When the particles of the present invention are incorporated into a formulation, it is preferably contained in an amount of 0.01 to 95% by weight, more preferably 0.01 to 90% by weight, still more preferably 0.1 to 50% by weight, and even more preferably 1 to 20% by weight based on the total composition constituting the formulation. When the particles of the present invention are incorporated into a formulation, it is preferably contained in an amount of 0.01 to 95% by weight, more preferably 0.01 to 90% by weight, still more preferably 0.1 to 50% by weight, and even more preferably 1 to 20% by weight based on the total composition constituting the formulation.

Examples

[0050] Next, examples will be described. First, the particles of the present invention themselves were examined (Examples 1 to 4), and then preparations using these particles were examined (Examples 5 to 7, Comparative Examples 1 to 3). However, the present invention is not limited thereto.

[0051] 〔Examination of the particles of the present invention〕 The particles of the present invention were each prepared according to the procedure shown below. And for each of the obtained particles , according to each of the following items, observation of the appearance (Examples 1 to 4), calculation of the particle size distribution (Examples 1, 2, 4), analysis of constituent sugars and lignin (Examples 1, 3, 4), Raman analysis (Examples 1, 4), evaluation of heat resistance, cold resistance and dryness resistance (Examples 1, 4), water dispersibility and storage stability evaluation (Examples 1, 4) were performed.

[0052] 〔Example 1〕 Licorice [roots and stolons, sometimes with the periderm removed (peeled licorice), manufactured by Enmoten Tenkaido Co., Ltd., Tokimoto's licorice P] was boiled and then immersed in water heated to 95°C, and heated for 50 minutes to obtain a lysate. Next, this lysate was centrifuged at 20,000 G to obtain a supernatant from which relatively large-sized contaminants were removed. This supernatant was centrifuged at 140,000 G to obtain aggregated particles A in pellet form. In order to increase the purity, the aggregated particles A in pellet form were dispersed in water, and this dispersion was centrifuged at 20,000 G for 20 minutes to remove contaminants, and the supernatant was filtered through a 0.45 μm filter (Merck Millipore-HV, 0.45 μm, PVDF), and the filtrate was further filtered through a 0.22 μm filter (Millex-GV, 0.22 μm, PVDF gamma-ray sterilized), and this filtrate was filtered through a 0.22 μm filter (Millex-GV, 0.22 μm, PVDF gamma-ray sterilized), and this filtrate was filtered through a 0.22 μm filter (Millex-GV, 0.22 μm, PVDF gamma-ray sterilized), and this filtrate was filtered through a 0.22 μm filter (Millex-GV, 0.22 μm, PVDF gamma-ray sterilized), and this filtrate was filtered through a 0.22 μm filter (Millex-GV, 0.22 μm, PVDF gamma-ray sterilized), and this The filtrate was centrifuged at 140,000 G to obtain a pellet, which is an aggregate of particle A with enhanced purity. 〔Fig. 1(a)〕

[0053] (Observation of appearance) This particle A was negatively stained, and a photograph taken with a transmission electron microscope is shown in Fig. 1(b). That is, particle A aggregated in pellet form with enhanced purity was dispersed in ultrapure water, and this dispersion was adsorbed onto a collodion-coated mesh (manufactured by Nisshin EM Co., Ltd.), and uranyl acetate (staining agent) was placed on it. Then, the excess uranyl acetate was blotted with filter paper and dried, and the resulting product was photographed with a transmission electron microscope (manufactured by JEOL Ltd., JEM-1400TC). As shown in Fig. 1(b), a typical particle A had a spherical shape with a maximum diameter of about 200 nm.

[0054] (Calculation of particle size distribution) Regarding the particle A aggregated in pellet form with enhanced purity, this was dispersed in ultrapure water, and its dispersion was used with a thick particle size analyzer (manufactured by Otsuka Electronics Co., Ltd., FPAR-1000) to calculate the particle size distribution by the histogram method. The results are shown in Fig. 1(c). As shown in Fig. 1(c ), the particle size of particle A showed a normal distribution with an average particle size of 193 nm.

[0055] (Analysis of constituent sugars) The analysis of the constituent sugars of the above particle A was performed as follows. That is, first, particle A aggregated in pellet form with enhanced purity was dried in a vacuum dryer at 60 °C for about 1 day, and the resulting product was used as a test sample (anhydrous basis). An appropriate amount (about 0.3 g) of this test sample was weighed into a beaker with a balance, 3 mL of 72% sulfuric acid was added, and the mixture was left for 1 hour while stirring at 30 °C. This reaction solution was diluted with 8 mL of purified water After completely transferring it to a pressure-resistant bottle while mixing with 4 mL, it was heated in an autoclave at 120 °C for 1 hour It decomposed. After thermal decomposition, the decomposition solution and the residue were filtered off, and the filtrate and the washing solution of the residue were added to make 100 mL The solution made up to volume was used as the test solution. Also, in order to correct for the over-decomposition of sugar during decomposition, a recovery rate test using monosaccharides was carried out in parallel Regarding the monosaccharides (rhamnose, ribose, xylose, ara binose, fructose, mannose, glucose, galactose) in the test solution, quantification was performed by high-performance liquid chromatography (fluorescence detector). The apparatus used for the analysis was a GL-7400 HPLC system manufactured by Jee Science Co., Ltd From the monosaccharide concentration of the obtained decomposition solution and the sample decomposition amount, the amount of constituent sugars in the sample was calculated. The results obtained are shown in Table 1 below Note that the results in Table 1 are those obtained by correcting the amount of constituent sugars using the sugar over-decomposition correction coefficient (S f) determined from the monosaccharide recovery rate test during decomposition. Also, since fructose is easily over-decomposed , Sf becomes a large value and the included error is large. Therefore, the amount of fructose after over-decomposition correction is treated as a reference value (for example, described as "※2" in Table 1 ). These are the same in the analysis of the following constituent sugars

[0056]

Table 1

[0057] As shown in Table 1 above for the analysis results of the constituent sugars of the above particle A, nearly 65% by weight of the constituent sugars is glucose, and in addition, it has fructose, galactose, arabino se, rhamnose, etc. This result correlates with the fact that many of the components constituting the cell wall of licorice are cellulose and hemicellulose. That is, cellulose ​​Cellulose is a natural polymer in which a large number of β-glucose molecules are polymerized linearly by glycosidic bonds and is decomposed into glucose by thermal decomposition. Hemicellulose is a general term for polysaccharides in which glucose and β-glucan etc. are combined and usually take a network structure, and by heating decomposition, it is decomposed not only into glucose but also into various sugars such as galactose . The analysis of the constituent sugars was carried out by using the product obtained by thermally decomposing particle A etc. as a test solution and measuring the monosaccharides in this test solution . The result that there is a lot of glucose and it contains various sugars such as galactose is not inconsistent with the fact that particle A contains a lot of cellulose and hemicellulose .

[0058] (Analysis of lignin) The analysis of the lignin in the above particle A was carried out as follows. Originally, in the measurement of lignin, it is a standard method to remove the soluble components (oil, tannin, polyphenol, etc.) in the sample with an organic solvent etc. beforehand , but extraction was not performed in the above analysis of lignin. That is, in the above analysis of lignin , as the quantification of acid-insoluble lignin, the residue obtained by filtration in the above constituent sugar analysis was dried at 105 °C and weighed to calculate the decomposition residue rate, and further, the ash content in the residue was measured and corrected to calculate the acid-insoluble lignin concentration. Also, as the quantification of acid-soluble lignin, the filtrate obtained by filtration in the above constituent sugar analysis was measured at a wavelength of 210 nm using a double-beam spectrophotometer (manufactured by Hitachi High-Technologies Corporation, U-2001 type), and the concentration was calculated according to the following formula (1) using the absorption coefficient of acid-soluble lignin of larch (plant name) . The obtained results are shown in Table 2 below. The absorption coefficient of larch lignin is known to be around 110 L·g -1·cm -1 -1 -1 . are known.

[0059]

Number

[0060]

Table 2

[0061] As shown in Table 2 above, the above-mentioned particle A has about 14 .0% by weight of acid-insoluble and acid-soluble lignin. From this result, it is also confirmed that particle A is derived from the cell wall of organisms belonging to the plant kingdom.

[0062] (Raman analysis) The Raman analysis of the above-mentioned particle A was performed on a sample with a small amount (about 0.5 mm square) of particle A placed on a slide glass using an inVia Reflex Raman microscope under the following conditions. That is, an LD excitation green laser (wavelength 532 nm) was used, with an objective lens magnification of 50 times, an irradiation laser beam diameter of 1.5 μm, an irradiation laser power of 1 mW or less , a photometric Raman shift range of 4000~150 cm , a wavenumber resolution of 6 cm -1 , an integration number of 10 times -1 , and the analysis was performed by library search through spectral waveform comparison and matching with a database . The obtained spectrum is shown in Figure 2.

[0063] As a result of the above analysis, it was found that the above-mentioned particle A has a spectrum close to that of cellulose. Cellulose is a polysaccharide component that constitutes the cell wall, and the constituent sugar is glucose. Also, a broad peak centered at 3500~3300 cm -1 is mainly attributed to the hydroxyl group , and at 2900 cm -1 ​​The peaks observed nearby are attributed to C-H bonds. Since both the hydroxyl group and the C-H bond are groups found in saccharides, it can be seen that particle A is derived from the cell wall of an organism belonging to the plant kingdom. And since both the hydroxyl group and the C-H bond are groups found in saccharides, it can be seen that particle A is derived from the cell wall of an organism belonging to the plant kingdom.

[0064] (Heat resistance, cold resistance, and drought resistance) First, the purified particle A dispersed in ultrapure water was freeze-dried [Figure 3(a)], and the dried product redispersed in ultrapure water [Figure 3(b)] was observed in the same manner as the above appearance observation [Figure 3(c)], and the particle size distribution was calculated using the above concentrated system particle size analyzer [Figure 3(d )]. Next, the freeze-dried product dispersed in ultrapure water [Figure 4(a)] was further heated and pressurized (121 °C, 20 minutes) using an autoclave, and observed in the same manner as the above appearance observation [Figure 4(b)], and the particle size distribution was calculated using the above concentrated system particle size analyzer [Figure 4(c)]. As a result of comparing and considering these results, no significant changes were observed in the appearance and particle size of particle A whether freeze-drying or heat pressurization was performed, indicating that particle A is excellent in heat resistance, cold resistance, and drought resistance.

[0065] (Water dispersibility and storage stability) The freeze-dried product dispersed in ultrapure water [Figure 4(a)] stored in an atmosphere at 4 °C for one week is shown in Figure 5(a). Also, particle A contained in the dispersion after this storage was observed in the same manner as the above appearance observation [Figure 5(b)], and the particle size distribution was calculated using the above concentrated system particle size analyzer [Figure 5(c)]. These results all show that no significant changes were observed in the appearance and particle size of particle A, indicating that the water dispersibility of particle A is maintained even after long-term low-temperature storage, and moreover, it has excellent storage stability.

[0066] ​​​​​​​ [Example 2] Using ginger (Zingiber officinale, manufactured by Toho Tenkaido Co., Ltd., ginger slices), pellets were obtained which were aggregates of Particle B with increased purity in the same manner as in Example 1. were obtained.

[0067] (Observation of appearance) In the same manner as in Example 1, a photograph of Particle B taken with a transmission electron microscope is shown in Fig. 6(a). According to Fig. 6(a), Particle B was a sphere with a maximum diameter of about 200 nm.

[0068] (Calculation of particle size distribution) For the Particle B aggregated in the form of the above pellets, the particle size distribution was calculated in the same manner as in Example 1. The result is shown in Fig. 6(b). As shown in Fig. 6(b), the particle size of Particle B showed a normal distribution with an average particle size of 230 nm.

[0069] [Example 3] Using Chlorella (Chlorella yaeyamaensis, manufactured by Yaeyama Shokusan Co., Ltd.), pellets were obtained which were aggregates of Particle C with increased purity in the same manner as in Example 1. Fig. 7(a) shows a photograph when pellets which are aggregates of Particle C with increased purity were obtained. were obtained.

[0070] (Observation of appearance) In the same manner as in Example 1, a photograph of Particle C taken with a transmission electron microscope is shown in Fig. 7(b). As shown in Fig. 7(b), Particle C was a sphere with a maximum diameter of about 400 nm.

[0071] (Analysis of constituent sugars) The analysis of the constituent sugars of the above Particle C was carried out in the same manner as in Example 1, except that about 0.15 g of Particle C was used as an appropriate amount of sample. The analysis results of the constituent sugars are shown in Table 3 below. ​​​​​

[0072]

Table 3

[0073] As shown in Table 3 above, nearly 60% by weight of the constituent sugars of Particle C is glucose. In addition, it also contains galactose, fructose, rhamnose, ribose, mannose, etc. This result, similar to that of licorice, correlates with the fact that many of the components constituting the cell wall of Chlorella are cellulose and hemicellulose. That is, the result of containing a large amount of glucose and various other sugars is not inconsistent with the fact that Particle C contains a large amount of cellulose and hemicellulose.

[0074] (Analysis of lignin) The analysis of the lignin of the above Particle C was carried out in the same manner as in Example 1, except that about 0.15 g of Particle C was used as an appropriate amount of sample. The analysis results of the lignin are shown in Table 4 below.

[0075]

Table 4

[0076] As shown in Table 4 above, Particle C contains about 6.1% by weight of lignin. This result also verifies that Particle C is derived from the cell wall of organisms belonging to the plant kingdom.

[0077] 〔Example 4〕 Using a mixture of the same amount of yeast (manufactured by MC Foods Specialties Co., Ltd., dried brewer's yeast) and yeast (manufactured by Nippon Garlit Co., Ltd., natural brewer's yeast), pellets, which are aggregates of Particle D with enhanced purity, were obtained in the same manner as in Example 1 [Figure 8(a)]. ​

[0078] (Observation of Appearance) In the same manner as in Example 1, a photograph of Particle D taken by a transmission electron microscope is shown in Fig. 8(b). As shown in Fig. 8(b), Particle D was a sphere with a maximum diameter of about 70 nm. .

[0079] (Calculation of Particle Size Distribution) For the particles D aggregated in the pellet form, the particle size distribution was calculated in the same manner as in Example 1. The results are shown in Fig. 8(c). As shown in Fig. 8(c), the particle size of Particle D showed a normal distribution with an average particle size of 66 nm.

[0080] (Analysis of Constituent Sugars) The analysis of the constituent sugars of the above Particle D was carried out in the same manner as in Example 1. The results are shown in Table 5 below. From the results shown in Table 5, almost all of the constituent sugars of the above Particle D were glucose. This result correlates with the fact that most of the yeast cell wall is composed of β-glucan and contains almost no hemicellulose and lignin. That is, since β-glucan is a polysaccharide consisting of only glucose, the above result is not inconsistent with the fact that Particle D contains a large amount of β-glucan and has no hemicellulose and lignin.

[0081]

Table 5

[0082] (Analysis of Lignin) The analysis of the lignin of the above Particle D was carried out in the same manner as in Example 1. The results are shown in Table 6 below. From the results shown in Table 6, the above Particle D contained almost no lignin. ​​​​It was found. From this result, it is also confirmed that particle D is derived from the cell wall of yeast. It is confirmed.

[0083]

Table 6

[0084] (Raman analysis) The Raman analysis of the above particle D was performed in the same manner as in Example 1. The obtained spectrum was shown in Fig. 9. As a result of the analysis, it was found that the above particle D has a spectrum similar to that of cellulose, which is a kind of β-glucan that is a constituent sugar of the yeast cell wall. Also, in Fig. 9, a broad peak centered around 3500 - 3300 cm mainly attributed to hydroxyl groups was observed, and a peak near 2900 cm attributed to C-H bonds was observed. Since both hydroxyl groups and C-H bonds are groups found in saccharides, it can be considered that particle D is derived from the yeast cell wall. -1 near 2900 cm -1

[0085] (Heat resistance, cold resistance and dryness resistance) First, the highly purified particle D dispersed in ultrapure water was freeze-dried [Fig. 10(a)]. Then, the freeze-dried product redispersed in ultrapure water [Fig. 10(b)] was observed in the same manner as the above external observation [Fig. 10(c)], and the particle size distribution was calculated using the above concentrated system particle size analyzer [Fig. 10(d)]. Next, the freeze-dried product redispersed in ultrapure water [Fig. 11(a)] was further heated and pressurized (121 °C, 20 minutes) in an autoclave, and observed in the same manner as the above external appearance observation [Fig. 11(b)], and the particle size distribution was calculated using the above concentrated system particle size analyzer [Fig. 11(c)]. As a result of comparing and considering these results, freeze-drying ​ Even when subjected to heating and pressurization, no significant change was observed in the appearance and particle size of Particle D, and it was found that Particle D is excellent in heat resistance, cold resistance, and dryness resistance.

[0086] (Water dispersibility and storage stability) A dispersion of the above lyophilized product in ultrapure water [Figure 10(b)] stored for one week in an atmosphere at 4°C is shown in Figure 12(a). Also, the particles D contained in the dispersion after this storage were observed in the same manner as the observation of the above appearance, and the result is shown in Figure 12(b). And the particle size distribution of the particles D contained in the dispersion after this storage was calculated using the above thick-system particle size analyzer, and the result is shown in Figure 12(c). All of these results indicate that no significant change was observed in the appearance and particle size of Particle D, and it was found that Particle D maintains its water dispersibility and is excellent in storage stability even after long-term storage.

[0087] 〔Examination of formulations using the particles of the present invention〕 Next, formulations (Examples 5 to 7) using the particles prepared in Examples 1, 3, and 4 and formulations (Comparative Examples 1 to 3) not using these particles were prepared, and the dissolution rate (%) of each was calculated. Also, for Example 7 and Comparative Example 3, the hardness and disintegration were measured.

[0088] 〔Example 5, Comparative Example 1〕 The particles A prepared in Example 1 and the following materials were prepared, and these materials were stirred and mixed. The resulting mixture was compressed at 6 kN using a tableting machine equipped with a mortar coated with magnesium stearate as a lubricant (manufactured by Ichihashi Seiki Co., Ltd., HANDTAB-100) to obtain Example 5, which is a 120 mg formulation (diameter 7 mm, radius of curvature 10 mm). Also, as Comparative Example 1, without using Particle A ​​​​​​​​​​​A 120 mg formulation was prepared in the same manner as in Example 5, except that lactose was used instead, (formulation without using the particles of the present invention). Table 7 below shows the formulations of Example 5 and Comparative Example 1. For Example 5 and Comparative Example 1, the dissolution rate (%) was calculated according to the following items.

[0089] [Table 7]

[0090] The results are shown in Table 8 below. (Calculation of dissolution rate (%))

[0091] (Calculation of dissolution rate (%)) Using a dissolution tester (manufactured by Toyama Sangyo Co., Ltd., NTR-3000), the dissolution rate (%) was calculated according to the dissolution test method of the 16th revised Japanese Pharmacopoeia. The above test was carried out by the paddle method using 900 mL of purified water as the test solution. Then, the test solution was sampled regularly until 60 minutes after the start of the test, and the solution passed through a 0.45 μm membrane filter was used as the measurement sample. The absorbance of each obtained measurement sample at 275 nm was measured using an ultraviolet-visible spectrophotometer (manufactured by Shimadzu Corporation, UV-1800). The obtained absorbance was applied to the following formula (2) to calculate the dissolution rate (%) at t minutes after the start of the test. The results are shown in Table 8 below. Using a dissolution tester (manufactured by Toyama Sangyo Co., Ltd., NTR-3000), the dissolution rate (%) was calculated according to the dissolution test method of the 16th revised Japanese Pharmacopoeia. The above test was carried out by the paddle method using 900 mL of purified water as the test solution. Then, the test solution was sampled regularly until 60 minutes after the start of the test, and the solution passed through a 0.45 μm membrane filter was used as the measurement sample. The absorbance of each obtained measurement sample at 275 nm was measured using an ultraviolet-visible spectrophotometer (manufactured by Shimadzu Corporation, UV-1800). The obtained absorbance was applied to the following formula (2) to calculate the dissolution rate (%) at t minutes after the start of the test. Using a dissolution tester (manufactured by Toyama Sangyo Co., Ltd., NTR-3000), the dissolution rate (%) was calculated according to the dissolution test method of the 16th revised Japanese Pharmacopoeia. The above test was carried out by the paddle method using 900 mL of purified water as the test solution. Then, the test solution was sampled regularly until 60 minutes after the start of the test, and the solution passed through a 0.45 μm membrane filter was used as the measurement sample. The absorbance of each obtained measurement sample at 275 nm was measured using an ultraviolet-visible spectrophotometer (manufactured by Shimadzu Corporation, UV-1800). The obtained absorbance was applied to the following formula (2) to calculate the dissolution rate (%) at t minutes after the start of the test. Using a dissolution tester (manufactured by Toyama Sangyo Co., Ltd., NTR-3000), the dissolution rate (%) was calculated according to the dissolution test method of the 16th revised Japanese Pharmacopoeia. The above test was carried out by the paddle method using 900 mL of purified water as the test solution. Then, the test solution was sampled regularly until 60 minutes after the start of the test, and the solution passed through a 0.45 μm membrane filter was used as the measurement sample. The absorbance of each obtained measurement sample at 275 nm was measured using an ultraviolet-visible spectrophotometer (manufactured by Shimadzu Corporation, UV-1800). The obtained absorbance was applied to the following formula (2) to calculate the dissolution rate (%) at t minutes after the start of the test. Using a dissolution tester (manufactured by Toyama Sangyo Co., Ltd., NTR-3000), the dissolution rate (%) was calculated according to the dissolution test method of the 16th revised Japanese Pharmacopoeia. The above test was carried out by the paddle method using 900 mL of purified water as the test solution. Then, the test solution was sampled regularly until 60 minutes after the start of the test, and the solution passed through a 0.45 μm membrane filter was used as the measurement sample. The absorbance of each obtained measurement sample at 275 nm was measured using an ultraviolet-visible spectrophotometer (manufactured by Shimadzu Corporation, UV-1800). The obtained absorbance was applied to the following formula (2) to calculate the dissolution rate (%) at t minutes after the start of the test. Using a dissolution tester (manufactured by Toyama Sangyo Co., Ltd., NTR-3000), the dissolution rate (%) was calculated according to the dissolution test method of the 16th revised Japanese Pharmacopoeia. The above test was carried out by the paddle method using 900 mL of purified water as the test solution. Then, the test solution was sampled regularly until 60 minutes after the start of the test, and the solution passed through a 0.45 μm membrane filter was used as the measurement sample. The absorbance of each obtained measurement sample at 275 nm was measured using an ultraviolet-visible spectrophotometer (manufactured by Shimadzu Corporation, UV-1800). The obtained absorbance was applied to the following formula (2) to calculate the dissolution rate (%) at t minutes after the start of the test. Dissolution rate (%) = Absorbance at t minutes after the start of the test / Absorbance at 60 minutes after the start of the test × 100... ( 2)

[0092] [Table 8]

[0093] From these results, for the entire mixture, with the addition of only 16.7% by weight of Particle A, a delay in the dissolution rate of about 2 times was confirmed at 30 minutes and 40 minutes after the start of the test. From this, From these results, for the entire mixture, with the addition of only 16.7% by weight of Particle A, a delay in the dissolution rate of about 2 times was confirmed at 30 minutes and 40 minutes after the start of the test. From this, Particle A was found to have the function as an additive for sustained-release tablets.

[0094] [Example 6, Comparative Example 2] Particle C prepared in Example 3 and the following materials were prepared, and these materials were stirred and mixed. The obtained mixture was made into a 120 mg formulation (diameter 7 mm, radius of curvature 10 mm ) in the same manner as in Example 5 to obtain Example 6. Also, as Comparative Example 2, a 120 mg formulation (a formulation not using the particles of the present invention) was prepared in the same manner as in Example 6 except that lactose was used instead of Particle C. The formulations of Example 6 and Comparative Example 2 are shown in Table 9 below.

[0095] [Table 9]

[0096] For Example 6 and Comparative Example 2, the dissolution rate (%) at t minutes after the start of the test was calculated according to the above items in the same manner as in Example 5 and Comparative Example 1. The results are shown in Table 10 below.

[0097] [Table 10]

[0098] From these results, for the entire mixture, by adding only 16.7% by weight of Particle C, a delay in the dissolution rate of about 2 times was confirmed at 10 minutes after the start of the test. From this, it was found that Particle C has the function as an additive for sustained-release tablets.

[0099] [Example 7, Comparative Example 3] Particle D prepared in Example 4 and the following materials were prepared, and these materials were stirred and mixed. The obtained mixture was compressed at 8 kN using a tableting machine (manufactured by Ichihashi Seiki Co., Ltd., HANDTAB-100). ​​​As a result, 200 mg of the preparation (diameter 8 mm, radius of curvature 12 mm) of Example 7 was obtained. As Comparative Example 3, 200 mg of Particles were prepared in the same manner as in Example 7, except that lactose was used instead of Particles D. The following formulations (without using the particles of the present invention) were prepared. The formulation of Comparative Example 3 is shown below.

[0100] [Table 11]

[0101] For Example 7 and Comparative Example 3, the above items were periodically checked up to 70 minutes after the start of the test. The test liquid was sampled and the absorbance was measured. The obtained value was applied to the following formula (3): The dissolution rate (%) after t minutes from the start of the test was calculated, and the results are shown in Table 12 below. Dissolution rate (%) = absorbance t minutes after the start of the test / absorbance 70 minutes after the start of the test × 100 ( 3)

[0102] [Table 12]

[0103] From these results, it was found that the addition of only 10% by weight of Particle D to the entire mixture reduced the It was confirmed that the dissolution rate increased by about 2 times between 5 minutes and 40 minutes. Therefore, it was found that particle D has a function as an additive for fast-dissolving and disintegrating tablets. .

[0104] In addition, for Example 7 and Comparative Example 3, the hardness and disintegration time were measured according to the following items. The results are shown in Table 13 below.

[0105] (Hardness measurement) Using a load cell type tablet hardness tester (manufactured by Okada Seiko Co., Ltd., Portable Checker PC-30), a load was gradually applied in the diameter direction of the preparation, and the load at the time of crushing of the preparation was measured as the hardness of the preparation. The measurement was performed with n = 5, and the average was adopted as the hardness of the preparation.

[0106] (Measurement of disintegration time) Using a disintegration tester (manufactured by Toyama Sangyo Co., Ltd., NT-200), the disintegration time (disintegratability) was measured according to the 16th revised Japanese Pharmacopoeia disintegration test method. In the above test, 1000 mL of purified water was used as the test solution, and the measurement temperature was 37 ± 2 °C. The time required for the preparation to disintegrate and disperse in the test solution was defined as the disintegration time.

[0107]

Table 13

[0108] From the results shown in Table 13 above, it was found that Example 7 had a higher hardness than Comparative Example 3. However, although Example 7 had a high hardness, the time until disintegration of the preparation was shorter than that of Comparative Example 3. That is, when the particles of the present invention are used in a preparation, they can be an extremely excellent additive that controls characteristics such as hardness, disintegratability, and drug elution properties.

[0109] In the above examples, specific forms of the present invention were shown, but the above examples are merely illustrative and are not to be construed in a limiting sense. Various modifications obvious to those skilled in the art are intended to be within the scope of the present invention.

Industrial applicability

[0110] ​​​​The particles of the present invention are suitable as additives for preparations typified by pharmaceuticals, foods, cosmetics, and the like.

Explanation of Signs

[0111] Particle A

Claims

1. Particles with a maximum diameter of 1 to 800 nm, obtained from components constituting a cell wall.

2. The particles according to Claim 1, wherein the particles obtained from components constituting a cell wall are spherical.

3. The particles according to Claim 1 or 2, wherein the particles obtained from components constituting a cell wall mainly contain sugar.

4. A method for producing the particles according to any one of Claims 1 to 3, comprising a step of lysing a cell wall and a step of separating particles from the lysate obtained by the step.

5. A method for producing the particles according to any one of Claims 1 to 3, comprising a step of preparing a liquid containing components constituting a cell wall and a step of separating particles from the liquid.

6. A composition characterized by containing the particles according to any one of Claims 1 to 3.

7. The composition according to Claim 6, wherein the composition is at least one selected from the group consisting of a pharmaceutical composition, a food composition, and a cosmetic composition. ​

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