JP7492837B2 - Composition - Google Patents

Description

The present invention relates to a composition, etc.

Perilla frutescens Britton var. crispa W. Deane (Labiatae) is the leaf and branch tip of the perilla plant, which has a slightly bitter taste and is said to have effects such as stimulant sweating, antipyretic, antitussive, sedative, analgesic, and diuretic properties. It is a highly useful ingredient that is used as an ingredient in various medicines, quasi-drugs, cosmetics, and the like, including gastrointestinal medicines (for example, Patent Document 1).
However, since Perilla herb contains various components derived from plants, stability problems such as changes in properties are likely to occur when it is formulated into pharmaceutical preparations.

JP 2015-214530 A

The objective of the present invention is to provide a new technology for stably formulating one or more selected from the group consisting of Perilla japonica and its extracts.

The inventors have conducted extensive research to solve the above problems, and have surprisingly found that by adding a metal hydroxide, such as aldioxa, to one or more of the perilla and its extracts, the changes in properties (such as discoloration) that may occur when the perilla and its extracts are stored under high-temperature conditions can be suppressed, and the one or more of the perilla and its extracts can be stabilized, thus completing the present invention.

That is, the present invention relates to a composition comprising the following components (A) and (B):
(A) one or more selected from the group consisting of Perilla japonica and extracts thereof;
(B) metal hydroxides;
The present invention provides a composition comprising:

According to the present invention, it is possible to provide a composition that is excellent in storage stability by suppressing changes in properties of one or more selected from the group consisting of Perilla japonica and its extracts when stored under high temperature conditions.

<Component (A)>
As described in the 17th Revised Japanese Pharmacopoeia, "Perilla frutescens" (Perilla leaves) are the leaves and branch tips of Perilla frutescens Britton var. crispa W. Deane (Labiatae), and either the leaves or the branch tips or both may be used in the present invention. The form of Perilla frutescens can be adjusted as necessary, and it can be cut or crushed into small pieces or small chunks, or crushed into powder. In addition, Perilla frutescens that has been subjected to some kind of extraction treatment (hereinafter referred to as "Perilla frutescens extract") may be used in consideration of the convenience of handling during the production of the composition.
The above-mentioned "extract of Perilla herb" includes those that have been subjected to processing such as heating, drying, crushing, etc., in addition to extraction. Specifically, the "extract of Perilla herb" of the present invention includes a liquid obtained by cutting Perilla herb into pieces of an appropriate size as necessary and then adding an appropriate extraction solvent to the resulting extract, a liquid obtained by concentrating the extract (soft extract, tincture, etc.), and further a liquid obtained by drying these (dried extract, etc.).
In the present invention, the one or more selected from the group consisting of Perilla japonica and extracts thereof is preferably a Perilla japonica dry extract.

There are no particular limitations on the method for producing the extract of Perilla herb, and it can be produced by referring to known methods for producing plant extracts, such as those described in the General Provisions for Preparations of the 17th Revised Japanese Pharmacopoeia, under the headings "Extracts," "Infusions/Decoctions," "Tinctures," and "Liquid Extracts." Specifically, for example, Perilla herb can be cut, heated, dried, crushed, etc. as necessary, and then extracted by adding an appropriate extraction solvent. The resulting extract can be further concentrated, dried, etc., as necessary.

Examples of the extraction solvent include lower monohydric alcohols such as methanol, ethanol, isopropanol, and n-butanol (preferably linear or branched aliphatic alcohols having 1 to 6 carbon atoms); lower polyhydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, and glycerin; ethers such as diethyl ether; ketones such as acetone and ethyl methyl ketone; esters such as ethyl acetate; nitriles such as acetonitrile; alkanes such as pentane, hexane, cyclopentane, and cyclohexane; halogenoalkanes such as dichloromethane and chloroform; aromatic hydrocarbons such as benzene and toluene; amides such as dimethylformamide; sulfoxides such as dimethyl sulfoxide; and water (including hot water). These may be used alone or in combination of two or more. In the present invention, the extraction solvent is preferably a solvent containing at least water or a linear or branched aliphatic alcohol having 1 to 6 carbon atoms, more preferably a solvent selected from water, a linear or branched aliphatic alcohol having 1 to 6 carbon atoms, and a mixture of water/linear or branched aliphatic alcohol having 1 to 6 carbon atoms, and particularly preferably a solvent selected from water, ethanol, and a mixture of water/ethanol.

The extraction procedure is not particularly limited, and any known method used for extraction from plants can be used, specifically, for example, immersion in an extraction solvent (cold immersion, hot immersion, percolation, etc.), extraction using a supercritical fluid or subcritical fluid, etc. In order to increase the extraction efficiency, stirring or homogenization in the extraction solvent may be performed.
The extraction temperature is not particularly limited and varies depending on the extraction solvent used, the extraction procedure, etc., but is preferably from about 5° C. to a temperature below the boiling point of the extraction solvent.
The extraction time is not particularly limited and varies depending on the extraction solvent used, the extraction procedure, etc., but is preferably about 1 hour to 14 days.

In addition, in the present invention, a Chinese herbal medicine prescription containing one or more selected from the group consisting of Perilla japonica and its extracts as an ingredient may be used. Specific examples of such Chinese herbal medicine prescriptions include Kososan, Soshi Koukito, Kakkoshoukisan, Bukryoingou Hange Koubokuto, Hange Koubokuto, etc.

In the present invention, one or more selected from the group consisting of Perilla japonica and extracts thereof may be commercially available products. Specific examples of commercially available products include Perilla japonica liquid extract and Perilla japonica leaf dried extract (both manufactured by Nippon Powder Pharmaceutical Co., Ltd.).

In the present invention, the content of one or more selected from the group consisting of Perilla herb and its extracts is not particularly limited, but is preferably 0.005 to 50% by mass in total, more preferably 0.01 to 5% by mass, even more preferably 0.1 to 2% by mass, and particularly preferably 0.3 to 1% by mass, based on the total mass of the composition. In addition, when the content of one or more selected from the group consisting of Perilla herb and its extracts is converted into the amount of raw herbal medicine, it is preferably 0.1 to 30% by mass in total, more preferably 1 to 15% by mass, and particularly preferably 3 to 10% by mass, based on the total mass of the composition.

<Component (B)>
In the present invention, the term "metal hydroxides" refers to a concept that includes components that contain a metal hydroxide in at least a part of the structure of the constituent components, and components (coprecipitation products) obtained by coprecipitation of the components as part of the raw materials. Here, examples of metals include alkali metals such as sodium and potassium; Group 2 elements such as magnesium and calcium; and Group 13 elements such as aluminum. Specific examples of such metal hydroxides include aldioxa, dihydroxyaluminum aminoacetate, magnesium alumina hydroxide, aluminum hydroxide, aluminum hydroxide gel, sodium hydroxide, magnesium hydroxide, dried aluminum hydroxide, dried aluminum hydroxide gel, aluminum hydroxide/sodium hydrogencarbonate coprecipitation product, aluminum hydroxide/magnesium carbonate mixed dry gel, aluminum hydroxide/magnesium carbonate/calcium carbonate coprecipitation product, magnesium hydroxide/aluminum potassium ammonium sulfate coprecipitation product, and sucralfate. In the present invention, the term "metal hydroxides" refers to the corresponding components that can be used alone or in appropriate combination of two or more kinds.
The metal hydroxides are known components and may be produced by known methods, or may be commercially available products. Specific examples of commercially available products include Aldioxa (manufactured by Permakem Asia Co., Ltd.), Glycinal (manufactured by Kyowa Chemical Industry Co., Ltd.), Dihydroxyaluminum Aminoacetate (manufactured by Tomita Pharmaceutical Co., Ltd.), Sanalmin (manufactured by Kyowa Chemical Industry Co., Ltd.), Aluminum Hydroxide (manufactured by Showa Denko Co., Ltd.), Aluminum Hydroxide Gel (manufactured by Tomita Pharmaceutical Co., Ltd.), Dried Aluminum Hydroxide Gel (manufactured by Kyowa Chemical Industry Co., Ltd.), and Sucralfate (manufactured by Ace Japan Co., Ltd.).

In the present invention, the metal hydroxides are preferably those containing aluminum hydroxide in at least a part of the structure of the constituent component and those obtained by coprecipitation of said component as part of the raw material, from the viewpoint of suppressing changes in the properties of one or more selected from the group consisting of Perilla japonica and its extracts, more preferably aldioxa, dihydroxyaluminum aminoacetate, magnesium alumina hydroxide, aluminum hydroxide, aluminum hydroxide gel, dried aluminum hydroxide, dried aluminum hydroxide gel, aluminum hydroxide/sodium hydrogencarbonate coprecipitation product, aluminum hydroxide/magnesium carbonate mixed dry gel, aluminum hydroxide/magnesium carbonate/calcium carbonate coprecipitation product, and sucralfate, and even more preferably aldioxa, dihydroxyaluminum aminoacetate, and sucralfate, and particularly preferably aldioxa.

In the present invention, the content of metal hydroxides is not particularly limited, but from the viewpoint of suppressing changes in the properties of one or more selected from the group consisting of Perilla japonica and its extracts, the content is preferably 1 to 60 mass% in total relative to the total mass of the composition, more preferably 5 to 40 mass%, and particularly preferably 10 to 20 mass%.

In the present invention, the mass ratio of the metal hydroxides to one or more selected from the group consisting of Perilla herb and its extracts is not particularly limited, but from the viewpoint of suppressing changes in the properties of one or more selected from the group consisting of Perilla herb and its extracts, it is preferable to contain 1 to 100 parts by mass of metal hydroxides per part by mass of one or more selected from the group consisting of Perilla herb and its extracts, more preferably 5 to 50 parts by mass, and particularly preferably 10 to 30 parts by mass. In addition, when the content of one or more selected from the group consisting of Perilla herb and its extracts is converted into the amount of raw herbal medicine, from the viewpoint of suppressing changes in the properties of one or more selected from the group consisting of Perilla herb and its extracts, it is preferable to contain 0.01 to 20 parts by mass of metal hydroxides per part by mass of Perilla herb and its extracts in raw herbal medicine equivalent, more preferably 0.1 to 10 parts by mass, and particularly preferably 1 to 5 parts by mass.

In the present invention, the "composition" may be in any form of solid, semi-solid, or liquid, and may be in a form that is generally used in medicines, quasi-drugs, cosmetics, foods, etc., depending on the intended use. Specifically, the composition may be in a dosage form described in the General Provisions for Preparations of the 17th Revised Japanese Pharmacopoeia, etc., such as solid preparations such as tablets (including orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, dissolving tablets, oral tablets (including lozenges, sublingual tablets, buccal tablets, adhesive tablets, and gums)), capsules, granules (including effervescent granules), powders, and pills; liquid preparations such as oral liquids (including elixirs, suspensions, emulsions, and lemonades), syrups, and oral liquids; and semi-solid preparations such as oral jellies and oral semi-solids.
In the present invention, from the viewpoint of suppressing changes in the properties of one or more selected from the group consisting of Perilla japonica and extracts thereof, a solid composition is preferred, a dosage form selected from the group consisting of tablets, capsules, granules, powders and pills is more preferred, and a dosage form selected from the group consisting of tablets and granules is particularly preferred.

The composition of the present invention can be produced according to the above-mentioned shape and dosage form in accordance with a method known in the fields of pharmaceuticals, quasi-drugs, cosmetics, food, etc., such as the method described in the General Provisions for Preparations in the 17th Edition of the Japanese Pharmacopoeia.
In addition to the above-mentioned components, the composition of the present invention may contain one or more carriers (such as excipients, binders, disintegrants, lubricants, colorants, flavoring agents, coating agents, etc.) used in the fields of pharmaceuticals, quasi-drugs, cosmetics, food, etc.

Examples of excipients include lactose, crystalline cellulose, sucrose, mannitol, and light anhydrous silicic acid.
Binders include hydroxypropylmethylcellulose, hydroxypropylcellulose, gelatin, polyvinylpyrrolidone, polyvinyl alcohol, pullulan, and the like.
Examples of disintegrants include carmellose, carmellose calcium, croscarmellose sodium, crospovidone, low-substituted hydroxypropyl cellulose and the like.
Lubricants include magnesium stearate, talc, and the like.
Examples of colorants include tar dyes and ferric oxide.
Flavoring agents include stevia, aspartame, etc.
Examples of the coating agent include film-forming polymers such as carboxymethylethylcellulose, cellulose acetate phthalate, methacrylic acid copolymer S, methacrylic acid copolymer L, methacrylic acid copolymer LD, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, etc. When forming a film, it is also possible to blend plasticizers such as triethyl citrate, triacetin, polyethylene glycol, etc.; and powders such as talc, titanium oxide, yellow ferric oxide, ferric oxide, legal dyes, light anhydrous silicic acid, and hydrous silicon dioxide.
In the present invention, one or more of these carriers can be used in appropriate combination.

The composition of the present invention may contain medicinal ingredients in addition to the above-mentioned ingredients. Such medicinal ingredients are not particularly limited and may be selected appropriately depending on the disease or symptoms to which the composition is applied. Examples of such ingredients include local anesthetics, digestive agents (cholagogues), digestive enzymes, gastric mucosa repair agents (mucosa protective ingredients), herbal ingredients, and antacids.

Local anesthetics include ethyl aminobenzoate, oxethazaine, and the like.
Digestive agents (cholagogues) include ursodeoxycholic acid, animal gall (bear gall, ox gall), and the like.
Examples of digestive enzymes include starch-digesting enzymes (biodiastase, takadiastase), fat-digesting enzymes (lipase), and the like.
Examples of gastric mucosa repairing agents (mucosa protecting components) include copper chlorophine sodium, copper chlorophine potassium, cetraxate hydrochloride, sofalcone, gefarnate, trimebutine maleate, and sodium azulene sulfonate.
The herbal ingredients include acacia, aniseed, aloe, fennel, turmeric, Ubai, Uyaku, Corydalis rotundifolia, Enmeisou, Scutellaria Root, Phellodendron Bark, Coptis Rhizome, processed garlic, zedoary, cuckoo, calamus root, kankyo, licorice, pheasant, solanum rhizome, cinnamon bark, Cassia japonica, gentian, geranium herb, red ginseng, Chinese pepper, Chinese pepper, peppercorn, chinese pepper, oak gall, colombo, condurago, hawthorn, Japanese pepper, wild mustard, and perilla. Examples of herbal medicines and extracts thereof include peony root, Chinese peony, ginger, cardamom, green bark, red cedar, acorus gramineus, centaurium grass, atractylodes rhizome, anemone, rhubarb, ginseng, clove, tangerine, chili pepper, spruce, bitter melon, nutmeg, carrot, mint, peppermint, long pepper, Atractylodes rhizome, hops, vomica, night cabbage leaf, yakuchi, morning glory, sage, and rhubarb.
Examples of antacids include proton pump inhibitors such as omeprazole, lansoprazole, and rabeprazole sodium; H2 receptor antagonists such as cimetidine, ranitidine hydrochloride, and famotidine; inorganic salts such as magnesium aluminosilicate, magnesium aluminometasilicate, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, sodium bicarbonate, magnesium carbonate, precipitated calcium carbonate, anhydrous calcium hydrogen phosphate, and calcium hydrogen phosphate; squid bone, stone ash, borey, aminoacetic acid, etc.
In the present invention, one or more of these medicinal ingredients can be appropriately combined and formulated.

The method of administration of the composition of the present invention is not particularly limited, and includes oral administration and parenteral administration, and may be appropriately selected depending on the intended use of the composition, but oral administration is preferred. The method of use and dosage of the composition are not particularly limited, and may be appropriately selected and determined depending on the intended use of the composition, the method of administration, the dosage form of the composition, and the like. The dosage is, for example, an amount that allows 1 to 200 mg, preferably 5 to 100 mg, and more preferably 10 to 50 mg of one or more selected from the group consisting of Perilla herb and its extracts per day. In addition, an amount that allows 10 to 1000 mg, more preferably 50 to 500 mg, and particularly preferably 100 to 300 mg of one or more selected from the group consisting of Perilla herb and its extracts per day in terms of crude drug is preferred.

Furthermore, in the present invention, the composition may be contained in an airtight package (hereinafter, in this specification, a composition contained in an airtight package is referred to as a "packaged composition"). As specifically disclosed in the test examples described later, by containing the composition of the present invention in an airtight package, it is possible to further suppress changes in the properties of one or more selected from the group consisting of Perilla japonica and its extracts. In this case, the packaged composition may further include a package other than the airtight package that does not fall under the below-mentioned "airtight package" (hereinafter, also referred to as "other package"), and the composition may be directly or indirectly contained in the airtight package. An example of an embodiment in which the composition is indirectly contained in an airtight package is an embodiment in which the composition is contained in the above-mentioned "other package" and then contained in the airtight package.

In this specification, "airtight packaging" means packaging that can prevent the intrusion of solid or liquid foreign matter under normal handling, transportation, storage, etc., and is a concept that includes "airtight containers" and "sealed containers" defined in the General Rules of the 17th Revised Japanese Pharmacopoeia. Airtight packaging can be of either a fixed or irregular shape, and specific examples include bottle packaging, SP (Strip Package) packaging, PTP (Press Through Package) packaging, pillow packaging, stick packaging, etc. Airtight packaging can also be a combination of these, and specific examples include a form in which the composition is first packaged in a PTP package and then further packaged in a pillow package.

The packaging material (raw material) of the airtight packaging body is not particularly limited, and may be, for example, glass, plastic (polyesters such as polyethylene terephthalate, polyethylene naphthalate, etc.; polyethylene (including low density (LDPE), medium density (MDPE), high density (HDPE)), polyolefins such as polypropylene, etc.; polycarbonate; polystyrene, etc.), metals (aluminum, etc.), etc., used in the fields of medicine, food, etc., either alone or in combination of two or more types.

For example, the packaging material used for bottle packaging is not particularly limited, and includes the above-mentioned glass, plastic, metal, etc., and one or more of these can be appropriately combined. As the material for bottle packaging, glass, polyethylene, and polypropylene are preferable, glass, low density polyethylene (LDPE), high density polyethylene (HDPE), and polypropylene are more preferable, glass, high density polyethylene (HDPE), and polypropylene are further preferable, and glass is particularly preferable.
In packaging in a bottle, for example, an appropriate amount of the composition is placed in the bottle, and then the bottle is sealed with an appropriate stopper or lid. The size of the bottle may be appropriately selected according to the amount of the composition to be placed, and the capacity of the bottle is, for example, about 10 to 500 mL, preferably 14 to 400 mL, and more preferably 24 to 350 mL.

In addition, the packaging materials used for SP packaging, PTP packaging, pillow packaging, stick packaging, etc. are not particularly limited, and examples include biaxially oriented polypropylene (OPP), biaxially oriented polyester (PET), glycol modified PET (PET-G), biaxially oriented nylon (ONy, PA), cellophane, paper, low density polyethylene (LDPE), linear low density polyethylene (L-LDPE), ethylene-vinyl acetate copolymer (EVA), unoriented polypropylene (CPP, IPP), ionomer resin (IO). , ethylene-methacrylic acid copolymer (EMAA), polyacrylonitrile (PAN), biaxially oriented polyvinylidene chloride (PVDC), ethylene-vinyl alcohol copolymer resin (EVOH), polyvinyl chloride (PVC), cyclic polyolefin (COC), non-oriented nylon (CNy), polycarbonate (PC), polystyrene (PS), rigid polyvinyl chloride (VSC), and other resins, as well as metal foils such as aluminum foil (AL), and these can be used alone or in combination of two or more types as appropriate.

When SP packaging, PTP packaging, pillow packaging, stick packaging, etc. are used, a sheet using one or more of the above-mentioned packaging materials may be produced by a known method, and in this case, a multi-layer structure may be formed by appropriately combining the packaging materials. An example of a method for producing a multi-layer structure using two or more packaging materials as a sheet is a method of laminating the packaging materials to produce a laminated sheet. The laminated sheet can be produced by known methods such as extrusion lamination, dry lamination, co-extrusion lamination, thermal lamination, wet lamination, non-solvent lamination, and heat lamination. Also, sheets for SP packaging, PTP packaging, pillow packaging, and stick packaging may be commercially available products known in the art.

Among the above sheets, examples of single-layer sheets using one type of packaging material include PVC sheets and CPP sheets, while examples of laminated sheets using two or more types of packaging materials include, but are not limited to, sheets with a laminate of PVC and PVDC (PVC/PVDC, hereafter abbreviated as such), PVC/PVDC/PE/PVC, PVC/PVDC/PE/PVDC/PVC, CPP/COC/CPP, PVC/PCTFE, CPP/PCTFE, PVC/AL/PA, PVC/AL, CPP/AL, CPP/CPP/CPP (the above sheets use two or more types of CPP), etc.

The form of PTP packaging may be such that the composition is stored in a desired number of pockets formed in a resin sheet or the like by a known method, one or one dosage unit at a time, and then the pockets are covered with a sheet made of a metal foil such as aluminum foil. The sheet used to form the pockets may also be a so-called double-sided aluminum PTP package, in which a sheet made of aluminum foil is used as the constituent material. When using PTP packaging, it is preferable to further package the PTP package in a pillow package (e.g., aluminum pillow package) from the viewpoint of suppressing changes in the properties of one or more selected from the group consisting of Perilla japonica and its extracts.
Examples of the form of SP packaging, pillow packaging, and stick packaging include packaging the composition one by one or one dosage unit by a known method using a resin sheet, a sheet made of aluminum foil, etc. In the case of SP packaging, pillow packaging, and stick packaging, it is preferable to use a sheet made of aluminum foil from the viewpoint of suppressing changes in the properties of one or more selected from the group consisting of Perilla japonica and its extracts.

In this specification, the occupancy rate (volume rate) of the composition in the packaged composition is usually 25 to 90%, preferably 28 to 75%, and more preferably 30 to 50%, when the package is a bottle package. When the package is a SP package, PTP package, pillow package, or stick package, the occupancy rate is usually 30 to 98%, preferably 40 to 95%, more preferably 45 to 93%, and particularly preferably 50 to 90%. In this case, the occupancy rate means the occupancy rate of the composition relative to the total volume inside the package, and fillers or inner stoppers, etc., used to prevent damage to the composition stored inside the package are not taken into consideration when calculating the space occupancy rate.

As the airtight packaging body, commercially available packaging bodies may be used as they are, or commercially available packaging materials may be processed and used. Examples of commercially available bottle packaging bodies include glass bottles (manufactured by Isoya Glass Industry Co., Ltd.), tablet bottles (manufactured by Tokyo Glass Co., Ltd.), and Z-series (manufactured by Hanshin Chemical Industry Co., Ltd.). Examples of commercially available pillow packaging bodies include Lamizip (registered trademark) (manufactured by Nippon Seisakusho Co., Ltd.). Furthermore, examples of packaging materials for SP packaging, PTP packaging, pillow packaging, and stick packaging include SUMILITE VSS, SUMILITE VSL, SUMILITE NS, and SUMILITE FCL (all manufactured by Sumitomo Bakelite Co., Ltd.), TAS series (manufactured by Taisei Kako Co., Ltd.), PTP vinyl foil, PTP super foil (all manufactured by Mitsubishi Plastics Co., Ltd.), Nippaku aluminum foil (manufactured by Nippon Foil Co., Ltd.), and plain silver aluminum foil (manufactured by Daiwa Chemical Industry Co., Ltd.).

The method for storing the composition in the airtight package is not particularly limited, and can be achieved by placing the composition in the package by any suitable means, such as by pouring the composition into the package. In this case, a means may be used in which a desiccant (e.g., a cylindrical (tablet) or sheet-shaped one) is poured into the package together with the composition.

The composition and packaged composition of the present invention can be used as medicines, quasi-drugs, cosmetics, foods, etc., and the purpose of use is not particularly limited. However, since it contains Perilla japonica, which has various pharmacological actions, it can be preferably used as a medicine, more preferably as a medicine for improving subjective symptoms and objective findings of gastric ulcers, duodenal ulcers, gastritis, etc., and improving liver function in chronic liver diseases. In addition, it can be preferably used as a gastrointestinal drug, more specifically, as a gastrointestinal drug with one or more efficacy and/or effects selected from the group consisting of stomach discomfort, weak stomach, heavy feeling, stomach pain, overeating, overdrinking, heartburn, nausea (retching, stomach retching, hangover, nausea from bad hangover, nausea, nausea), vomiting, loss of appetite, indigestion, hyperacidity, belching, chest tightness, digestion promotion, stomach and/or abdominal bloating, and stomach heaviness.

The present invention also relates to the following component (A):
(A) one or more selected from the group consisting of Perilla japonica and extracts thereof;
and the following component (B):
(B) metal hydroxides;
and a method for stabilizing one or more selected from the group consisting of Perilla edulis and extracts thereof in a composition (preferably a method for suppressing changes in properties (preferably discoloration and/or solidification) of one or more selected from the group consisting of Perilla edulis and extracts thereof in a composition), the method comprising the step of incorporating both in the same composition.
In the invention of such an embodiment, the order of the step of incorporating component (A) and the step of incorporating component (B) is not particularly limited, as long as a composition containing components (A) and (B) is produced directly or indirectly.
In this embodiment of the invention, the meanings of various terms, the amounts of each component, etc. are all the same as those explained for the "composition" above.

In addition, the present specification discloses the following aspects of the invention, for example, but is not limited to these.
[1A] The following components (A) and (B):
(A) one or more selected from the group consisting of Perilla japonica and extracts thereof;
(B) metal hydroxides;
A composition comprising:
[2A] The composition according to [1A], wherein the extract of Perilla japonica is obtained by using water or a solvent containing a linear or branched aliphatic alcohol having 1 to 6 carbon atoms as an extraction solvent.
[3A] The composition according to [1A] or [2A], wherein component (B) is one or more members selected from the group consisting of aldioxa, dihydroxyaluminum aminoacetate, magnesium alumina hydroxide, aluminum hydroxide, aluminum hydroxide gel, dried aluminum hydroxide, dried aluminum hydroxide gel, aluminum hydroxide-sodium hydrogencarbonate co-precipitation product, aluminum hydroxide-magnesium carbonate mixed dry gel, aluminum hydroxide-magnesium carbonate-calcium carbonate co-precipitation product, and sucralfate.
[4A] The composition according to any one of [1A] to [3A], which is a solid composition.
[5A] The composition according to any one of [1A] to [4A], which is in a dosage form selected from the group consisting of tablets, capsules, granules, powders, and pills.
[6A] The composition according to any one of [1A] to [5A], which is a gastrointestinal drug.

[1B] A packaged composition comprising the composition according to any one of [1A] to [6A] contained in an airtight package.
[2B] The packaged composition according to [1B], wherein the airtight package is one or more selected from the group consisting of bottle packaging, SP packaging, PTP packaging, pillow packaging and stick packaging.

[1C] The following component (A):
(A) one or more selected from the group consisting of Perilla japonica and extracts thereof;
and the following component (B):
(B) metal hydroxides;
A method for stabilizing one or more selected from the group consisting of Perilla japonica and extracts thereof in a composition, comprising the step of incorporating both in the same composition (preferably a method for inhibiting changes in properties, particularly preferably a method for inhibiting discoloration and/or solidification).
[2C] The method according to [1C], wherein the extract of Perilla herb is obtained by using water or a solvent containing a linear or branched aliphatic alcohol having 1 to 6 carbon atoms as an extraction solvent.
[3C] The method according to [1C] or [2C], wherein component (B) is one or more selected from the group consisting of aldioxa, dihydroxyaluminum aminoacetate, magnesium alumina hydroxide, aluminum hydroxide, aluminum hydroxide gel, dried aluminum hydroxide, dried aluminum hydroxide gel, aluminum hydroxide/sodium hydrogencarbonate co-precipitation product, aluminum hydroxide/magnesium carbonate mixed dry gel, aluminum hydroxide/magnesium carbonate/calcium carbonate co-precipitation product, and sucralfate.
[4C] The method according to any one of [1C] to [3C], wherein the composition is in a solid form.
[5C] The method according to any one of [1C] to [4C], wherein the composition is in a dosage form selected from the group consisting of tablets, capsules, granules, powders and pills.
[6C] The method according to any one of [1C] to [5C], wherein the composition is a gastrointestinal drug.

[1D] The method according to any one of [1C] to [6C], further comprising a step of housing the composition obtained in the above step in an airtight package.
[2D] The method according to [1D], wherein the airtight packaging is one or more selected from the group consisting of bottle packaging, SP packaging, PTP packaging, pillow packaging, and stick packaging.

The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these in any way. In the following examples, the amounts (parts by mass) of various components indicate the amounts obtained by weighing the various components as they are, unless the converted amounts are specified.

[Test Example 1] Stability test Part 1
Each sample shown below was placed in a glass bottle (A-102K: manufactured by Isoya Glass Industry Co., Ltd.) and stored without a lid at 60° C. for two days. The condition of the sample was visually inspected before the start of storage and after the two-day storage, and the changes in the properties of the sample before and after storage were evaluated.
The results are shown in Table 1.

[Sample 1]
Perilla dried extract (Perilla dried extract-Q: manufactured by Nippon Powder Pharmaceutical Co., Ltd.) was used as it was as Sample 1.
[Sample 2]
One part by mass of Perilla dried extract (Perilla dried extract-Q: manufactured by Nippon Powder Pharmaceutical Co., Ltd.) was mixed with one part by mass of Aldioxa (Aldioxa: manufactured by Permachem Asia Co., Ltd.), and the resulting mixture was designated as Sample 2.

The test results shown in Table 1 confirm that, when the perilla dried extract alone (Sample 1) was stored at 60°C for two days, discoloration to a dark brown occurred, whereas when the perilla dried extract was mixed with aldioxane (Sample 2), such discoloration was inhibited.
From the above test results, it has become clear that by coexisting one or more substances selected from the group consisting of Perilla japonica and its extracts with metal hydroxides such as aldioxa, changes in the properties of one or more substances selected from the group consisting of Perilla japonica and its extracts can be suppressed.

[Test Example 2] Stability test No. 2
Each sample shown below was placed in a glass bottle (A-102K, manufactured by Isoya Glass Industry Co., Ltd.), and sample 3 was left uncapped, while sample 4 was capped and airtightly packaged, and stored for 3 days under conditions of 40°C and 75% relative humidity (RH). The condition of the samples was visually inspected before the start of storage and after storage for 3 days, and changes in the properties of the samples before and after storage were evaluated.
The results are shown in Table 2.

[Sample 3]
Perilla dried extract (Perilla dried extract-Q: manufactured by Nippon Powder Pharmaceutical Co., Ltd.) was used as sample 3 as it was.
[Sample 4]
One part by mass of Perilla dried extract (Perilla dried extract-Q: manufactured by Nippon Powder Pharmaceutical Co., Ltd.) was mixed with one part by mass of Aldioxa (Aldioxa: manufactured by Permachem Asia Co., Ltd.), and the resulting mixture was designated as Sample 4.

The test results shown in Table 2 confirm that when the perilla dried extract alone (Sample 3) was stored at 40°C and 75% RH for three days, it discolored to a dark brown and also solidified, whereas when the mixture of perilla dried extract and aldioxa was stored in an airtight package (bottle package) (Sample 4), both discoloration and solidification were suppressed.
From the above test results, it has become clear that by coexisting one or more substances selected from the group consisting of Perilla japonica and its extracts with metal hydroxides such as aldioxa and storing them in an airtight package, changes in the properties of one or more substances selected from the group consisting of Perilla japonica and its extracts can be further suppressed.

[Production Example 1]
Tablets weighing 680 mg each containing the following ingredients were produced in a conventional manner and placed in low-density polyethylene bottles.
Perilla dried extract 1.7mg (equivalent to 15mg of crude drug)
Aldioxa 50mg
Dihydroxyaluminum aminoacetate 200mg
Magnesium alumina hydroxide 100mg
Dry aluminum hydroxide 150mg
Hydroxypropyl cellulose, hydrogenated oil, carmellose calcium, corn starch, magnesium stearate, glycerin monostearate, polyoxyl stearate, shellac, talc, cinnamon, polyvinyl alcohol (partially saponified)
Cellulose Silicon dioxide l-menthol

[Production Example 2]
Granules (1,300 mg each) containing the following ingredients per packet were prepared in a conventional manner and packaged in strip-packaging aluminum foil (Nissan Kako Co., Ltd.).
Perilla Root Dry Extract 6.6mg (60mg equivalent of raw herb)
Aldioxa 100mg
Sucralfate 500mg
Dried aluminum hydroxide gel 150 mg
Aluminum hydroxide 50mg
Hydrogenated oil Hydroxypropyl cellulose D-mannitol Carmellose calcium Calcium lactate Sucralose l-menthol Flavor Corn starch

The present invention provides a composition that contains one or more selected from the group consisting of Perilla japonica and its extracts, which have various pharmacological actions, and has excellent storage stability, and can be used, for example, in the pharmaceutical industry.

Claims (5)

The following components (A) and (B):
(A) one or more selected from the group consisting of Perilla japonica and extracts thereof;
(B) aldioxa ;
A composition comprising: The composition of claim 1 which is a solid composition. 3. The composition according to claim 1 or 2 , which is in a dosage form selected from the group consisting of tablets, capsules, granules, powders and pills. A packaged composition comprising the composition according to any one of claims 1 to 3 contained in an airtight package. 5. The packaged composition according to claim 4 , wherein the airtight package is at least one selected from the group consisting of a bottle package, a SP package, a PTP package, a pillow package and a stick package.