TWI829731B - Composition - Google Patents

Abstract

The present invention provides a novel means for stabilizing methionine chloride in a composition.

The composition of the present invention contains the following components (A) and (B):

(A) Methionine chloride;

(B) One or more species selected from the group consisting of Magnolia officinalis and its extracts.

Description

Composition

The present invention relates to compositions containing methionine chloride and the like.

Methionine chloride (hereinafter sometimes also referred to as "MMSC") has a protective effect on the mucosa of the digestive tract, and is therefore used for: improvement of subjective and other symptoms such as gastric ulcer, duodenal ulcer, and gastritis; liver disease of chronic liver disease Function improvement, etc., and is widely used as an ingredient in gastrointestinal medicine.

However, MMSC is unstable and tends to decrease in content over time. Therefore, compositions containing MMSC have problems such as quality degradation over time.

Known means for stabilizing MMSC in the composition include, for example, means of containing MMSC and vitamin B1 or its derivatives or salts thereof in the same preparation (Patent Document 1); applying MMSC to bare tablets containing MMSC. After the protective layer, a sugar-coating composition liquid containing succinic gelatin is further coated to form a sugar-coated preparation (Patent Document 2); and a method of mixing polysiloxane with MMSC to obtain a mixed powder is used (Patent Document 3) ; A sugar coating preparation having a core material containing MMSC and a sugar coating layer covering the core material, and at least one layer of the sugar coating layer is a sugar coating containing 0.01 to 10% by weight of sugar and ethyl acrylate‧methyl methacrylate copolymer. Preparation means (Patent Document 4), etc.

[Prior technical literature] [Patent Document]

[Patent Document 1] Japanese Patent Application Publication No. 2010-30964

[Patent Document 2] Japanese Patent Application Publication No. 2003-63953

[Patent Document 3] Japanese Patent Application Laid-Open No. 2003-306431

[Patent Document 4] International Publication No. 08/13084

An object of the present invention is to provide a novel means for stabilizing methionine chloride in a composition.

In view of this fact, the inventors conducted in-depth research and surprisingly found that one or more types selected from the group consisting of Magnolia officinalis and its extracts (hereinafter sometimes also referred to as "ingredient (B)") have inhibitory effects The present invention is completed by reducing the content of methionine chloride (hereinafter sometimes referred to as "component (A)") and stabilizing it.

That is, the composition provided by the present invention contains the following components (A) and (B):

(A) Methionine chloride;

(B) One or more species selected from the group consisting of Magnolia officinalis and its extracts.

According to the present invention, it is possible to provide a composition with excellent quality and stability in which the content of methionine chloride is suppressed and the stability is improved.

<Ingredients (A)>

"Methionine chloride" is also a component known as vitamin U. In the present invention, commercially available MMSC systems can be used. Specific commercially available products include, for example, U-BIT "HAMARI WAI" (manufactured by Yonezawa Hamari Pharmaceutical Co., Ltd.).

In the present invention, the content of MMSC is not particularly limited. From the viewpoint of the expected medicinal effect, it is preferably 0.05 to 50 mass %, more preferably 0.1 to 10 mass %, based on the total mass of the composition. The best series contains 1 to 7.5 mass%, and the optimal series contains 2.5 to 5 mass%.

<Ingredients (B)>

"Magnolia Bark" refers to Magnolia obovata Thunberg (Magnolia hypoleuca Siebold et Zuccarini), Magnolia officinalis Rehder et Wilson, or Magnolia officinalis Rehder et Wilson var. biloba Rehder et Wilson (Magnoliaceae)). The shape of Magnolia officinalis can be adjusted as needed, and it can be cut or crushed into small pieces, small pieces, or crushed into powder. In addition, if the convenience of handling during the production of the composition is taken into consideration, those that have been subjected to any extraction process on Magnolia officinalis (hereinafter referred to as "Magnolia officinalis extract") can also be used.

In addition, the above-mentioned "Magnolia bark extract" includes those that have been subjected to processing such as heating, drying, and grinding in addition to extraction. Specifically, Magnolia officinalis is formed into an appropriate size as necessary, and then an appropriate extraction solvent is added to exude the liquid; and the liquid in which the exudate is concentrated (soft extract, tincture, etc.); furthermore, the liquid is dried ( Dried extract, etc.) are all included in the "Magnolia officinalis extract" of the present invention.

In the present invention, at least one type selected from the group consisting of Magnolia officinalis and its extracts is preferably a dried extract of Magnolia officinalis.

There are no special restrictions on the manufacturing method of magnolia bark extract. For example, you can refer to the items "Extraction Agent", "Soaking Agent/Decoction", "Tincture", and "Flowing Extract") in the 17th edition of the revised Japanese Pharmacopoeia General Preparations There are known methods for producing plant extracts, such as those described in the above. Specifically, for example, Magnolia officinalis may be cut, heated, dried, pulverized, etc. if necessary, and then an appropriate extraction solvent may be added and extraction may be performed. The obtained extract can be further concentrated, dried, etc. if necessary.

Examples of the above-mentioned extraction solvent include: lower monohydric alcohols such as methanol, ethanol, isopropanol, and n-butanol; lower polyhydric alcohols such as ethylene glycol, propylene glycol, 1,3-butanediol, and glycerin; ethers such as diethyl ether; Acetone, methyl ethyl ketone and other ketones; ethyl acetate and other esters; acetonitrile and other nitriles; pentane, hexane, cyclopentane, cyclohexane and other alkanes; methylene chloride, chloroform and other halogenated alkanes; benzene, toluene, etc. Aromatic hydrocarbons; amides such as dimethyl formamide; dimethyl sulfoxide and other sulfoxides; water (including hot water), etc. These may be used individually or in combination of 2 or more types. In the present invention, it is preferably a lower monohydric alcohol (more preferably a lower monohydric alcohol having 1 to 6 carbon atoms), water, or a mixed liquid thereof, and particularly preferably ethanol, water, or a mixed liquid of water and ethanol.

The extraction operation is not particularly limited, and any known method used in extraction operations from plants can be adopted. Specific examples include: dipping (cold soaking, warm soaking, percolation, etc.) in the extraction solvent; and using supercritical Extraction of fluids or subcritical fluids, etc. In addition, in order to improve the extraction efficiency, stirring or homogenization in the extraction solvent can also be performed.

The extraction temperature is not particularly limited and varies depending on the extraction solvent used, the extraction operation, etc., but it is preferably set to a temperature between about 5°C and 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 operation, etc., but it is preferably set to about 1 hour to 14 days.

Furthermore, in the present invention, one or more species selected from the group consisting of Magnolia officinalis and its extracts may be used, and a traditional Chinese medicine prescription containing these components may also be used. Specific examples of such traditional Chinese medicine prescriptions include: Pinellia Magnolia Decoction, Magnolia Ginger Pinellia Ginseng Licorice Decoction, Xiangsha Pingwei Powder, Chaipu Decoction, Xiaochengqi Decoction, Poria Yin combined with Pinellia Magnolia Decoction, etc.

In the present invention, commercially available products can be used as one or more types selected from the group consisting of Magnolia officinalis and its extracts. Specific commercially available products include, for example: Magnolia officinalis dried extract, Magnolia officinalis dried extract- S. Magnolia officinalis extract, Magnolia officinalis extract-A, Magnolia officinalis extract, (pharmacopoeia) Magnolia officinalis powder (the above are all manufactured by Japan Powder Pharmaceutical Co., Ltd.), etc.

In the present invention, the content of one or more selected from the group consisting of Magnolia officinalis and its extracts is not particularly limited. From the viewpoint of suppressing the decrease in MMSC content, relative to the total mass of the composition, it is preferable to contain 0.01~60% by mass, more preferably 0.05~5% by mass, and more preferably 0.1~1% by mass. Furthermore, when the content of one or more selected from the group consisting of Magnolia officinalis and its extracts is converted into a native dosage, from the viewpoint of suppressing the decrease in MMSC content, from the group consisting of Magnolia officinalis and its extracts, One or more species selected from the composition, preferably contains 0.1 to 800 mass %, more preferably 1 to 600 mass %, particularly preferably 2 to 50 mass % based on the original drug conversion amount relative to the total mass of the composition. The optimal system contains 3 to 7% by mass.

Furthermore, the content ratio by mass of MMSC and one or more selected from the group consisting of Magnolia officinalis and its extract is not particularly limited. From the viewpoint of suppressing the decrease in MMSC content, relative to MMSC: 1 part by mass, One or more preferred systems selected from the group consisting of Magnolia officinalis and its extracts contain 0.001 to 10 parts by mass, a more preferred system contains 0.005 to 5 parts by mass, a particularly preferred system contains 0.01 to 3 parts by mass, and the most preferred system contains 0.001 to 3 parts by mass. Contains 0.05~2.5 parts by mass. In addition, when converted into a native drug amount, the content of one or more selected from the group consisting of Magnolia officinalis and its extracts, from the viewpoint of suppressing the decrease in MMSC content, is: 1 part by mass relative to MMSC, from Magnolia officinalis One or more selected from the group consisting of its extracts, based on the original drug conversion amount, the preferred system contains 0.01 to 20 parts by mass, the more preferred system contains 0.1 to 10 parts by mass, and the particularly preferred system contains 0.5 to 5 parts by mass.

In the composition of the present invention, from the viewpoint of suppressing the decrease in MMSC content, in addition to MMSC and one or more selected from the group consisting of Magnolia officinalis and its extract, it may further optionally contain: Perilla leaves and One or more types selected from the group consisting of extracts (hereinafter sometimes also referred to as "ingredient (C)"), and selected from the group consisting of starches (hereinafter sometimes referred to as "ingredient (D)") More than 1 species. As specifically revealed in the test examples described later, it was found that in addition to MMSC and one or more selected from the group consisting of Magnolia officinalis and its extracts, by further selecting from the group consisting of Perilla leaves and its extracts, it was found that Selecting more than one type, or coexisting starch, can further suppress the decrease in MMSC content.

<Ingredients (C)>

The "Perilla Herb" optionally contained in the composition of the present invention refers to Perilla frutescens Britton var. acuta Kudo or Perilla frutescens as recorded in the 16th edition of the revised Japanese Pharmacopoeia. The leaves and branches of Britton var.crispa Decaisne (Labiatae). The shape of perilla leaves can be adjusted as needed, and can be cut or crushed into small pieces, small pieces, or crushed into powder. In addition, if the convenience of handling during the production of the composition is taken into consideration, perilla leaves that have been subjected to any extraction process (hereinafter referred to as "perilla leaf extracts") may be used.

In addition, in addition to the extraction process, the above-mentioned "perilla leaf extract" also includes those that have been subjected to processing such as heating, drying, and crushing. Specifically, after perilla leaves are formed into an appropriate size as needed, a suitable extraction solvent is added to the exudate liquid; and the liquid in which the exudate is concentrated (soft extract, tincture, etc.); and further dried (dried Extracts, etc.) are all included in the "perilla leaf extract" of the present invention.

In the present invention, at least one selected from the group consisting of perilla leaves and their extracts is preferably a dried perilla leaf extract.

The method for producing the perilla leaf extract is not particularly limited. For example, it can be produced by the same method as the above-mentioned method for producing the Magnolia officinalis extract.

Furthermore, in the present invention, one or more types selected from the group consisting of perilla leaves and their extracts can also be used in traditional Chinese medicine prescriptions containing these ingredients. Specific examples of such traditional Chinese medicine prescriptions include: Xiangsu powder, Suzi Jiangqi decoction, Huoxiang Zhengqi powder, Poria decoction combined with Banxia Houpu decoction, Banxia Houpu decoction, etc.

In the present invention, one or more species selected from the group consisting of perilla leaves and their extracts may be commercially available products. Specific commercially available products include, for example: perilla leaf liquid extract and perilla leaf dried extract. (The above are all manufactured by Japan Powder Pharmaceutical Co., Ltd.) etc.

In the present invention, the content of one or more selected from the group consisting of perilla leaves and their extracts is not particularly limited. From the viewpoint of suppressing the decrease in MMSC content, relative to the total mass of the composition, it is preferable to contain 0.01~50% by mass, more preferably 0.05~5% by mass, and more preferably 0.1~3% by mass. In addition, when the content of one or more selected from the group consisting of perilla leaves and their extracts is converted into a native dosage, from the viewpoint of the effect of inhibiting the reduction of MMSC content, the content of perilla leaves and their extracts constituted One or more species selected from the group should preferably contain 0.1 to 800 mass %, more preferably 1 to 600 mass %, and particularly preferably 2 to 50 mass % in terms of raw drug conversion relative to the total mass of the composition. Mass %, the optimal system contains 3 to 7 mass %.

Furthermore, the content ratio by mass of MMSC and one or more selected from the group consisting of perilla leaves and their extracts is not particularly limited. From the viewpoint of suppressing the decrease in MMSC content, relative to MMSC: 1 part by mass, At least one type selected from the group consisting of perilla leaves and their extracts, preferably contains 0.001 to 50 parts by mass, more preferably 0.01 to 5 parts by mass, and particularly preferably 0.05 to 1 part by mass. Furthermore, from the viewpoint of suppressing the decrease in MMSC content, the content of one or more species selected from the group consisting of perilla leaves and their extracts is converted into a native dosage, relative to MMSC: 1 part by mass, from perilla leaves One or more species selected from the group consisting of its extracts, preferably containing 0.1 to 10 parts by mass, more preferably 0.01 to 15 parts by mass, and particularly preferably 0.5 to 5 parts by mass in terms of native drug conversion. share.

Furthermore, the content mass ratio of one or more types selected from the group consisting of Magnolia officinalis and its extracts and one or more types selected from the group consisting of Perilla leaves and its extracts is not particularly limited. From the viewpoint of suppressing the decrease in MMSC content, 1 or more types selected from the group consisting of Magnolia officinalis and its extracts is more The optimal system contains 0.01 to 10 parts by mass, the more optimal system contains 0.05 to 5 parts by mass, and the particularly optimal system contains 0.1 to 2 parts by mass. In addition, when the content of the two components is converted into the original drug amount, from the viewpoint of suppressing the decrease in the MMSC content, 1 mass is calculated as the original drug conversion amount relative to one or more types selected from the group consisting of Magnolia officinalis and its extracts. parts, one or more selected from the group consisting of perilla leaves and their extracts, based on the original drug conversion amount, the preferred system contains 0.01 to 10 parts by mass, the more preferred system contains 0.1 to 5 parts by mass, and the particularly preferred system contains 0.5~2 parts by mass.

<Ingredients (D)>

The "starches" that can be optionally contained in the composition of the present invention refer to the group consisting of starch itself, those forming ether bonds from all or part of the hydroxyl groups of starch, their derivatives, and their salts. Choose from 1 or more types. In addition, starch also includes those that have been processed by gelatinization, aging, etc. In addition, the above-mentioned derivatives also include starch or its etherified products, which are further modified by esterification, cross-linking formation, hydrolysis, etc. if necessary. The salt here is not particularly limited, and specific examples include alkali metal salts such as sodium salts and potassium salts; salts of Group 2 elements such as calcium salts and magnesium salts.

Specific examples of such starches include: starches such as α-starch, wheat starch, rice starch, corn starch, potato starch, partially α-starch, wheat flour, rice flour, semi-digested starch, or their salts; hydroxypropyl starch Hydroxyalkyl ethers of starches such as sodium carboxymethyl starch or salts thereof; carboxyalkyl ethers of starches such as sodium carboxymethyl starch or salts thereof, etc. Among these, one type may be used alone or two or more types may be used in combination. In addition, the alkyl group of the starch is not particularly limited, but is preferably a linear or branched chain alkyl group having 1 to 6 carbon atoms.

From the viewpoint of suppressing the decrease in MMSC content, the starch is preferably at least one selected from the group consisting of starch, hydroxyalkyl ether of starch, carboxyalkyl ether of starch, and salts thereof, and more preferably At least one selected from the group consisting of starch, hydroxy C1-C6 alkyl ether of starch, carboxyl C1-C6 alkyl ether of starch, and salts thereof, more preferably, one selected from the group consisting of starch, hydroxypropyl starch and carboxymethyl starch, and salts thereof. Particularly preferred is at least one selected from the group consisting of starch and carboxymethyl starch sodium. The most preferred is corn starch.

In addition, these starches are all known components and can be produced by known methods, and commercially available products can also be used. Examples of such commercially available products include LYCA TAB PGS (ROCKET JAPAN Co., Ltd.); GLYCOLYS (ROCKET JAPAN Co., Ltd.); starch (soluble) (Kishida Chemical Co., Ltd.); corn starch (Saneigen F.F.I. (Saneigen F.F.I.)); (Stock)); potato starch (Junsheng Chemical (Stock)); HPS-101 (FREUND Industrial (Stock)); LYCATABC (ROCKET JAPAN (Stock)), etc.

In the present invention, the content of starch is not particularly limited. From the viewpoint of suppressing a decrease in MMSC content, it is preferably 0.01 to 40 mass %, more preferably 0.05 to 20 mass %, based on the total mass of the composition. The best series contain 0.1~10% by mass.

Furthermore, the mass ratio of MMSC and starch is not particularly limited. From the viewpoint of suppressing the decrease in MMSC content, starch is preferably contained in a range of 0.01 to 10 parts by mass, and more preferably 1 part by mass of MMSC. 0.1~5 parts by mass, the best series contains 0.5~3 parts by mass.

Furthermore, the mass ratio of the content of one or more species selected from the group consisting of Magnolia officinalis and its extracts to starch is not particularly limited. From the viewpoint of suppressing the decrease in MMSC content, compared to the content of Magnolia officinalis and its extracts, the content ratio is not particularly limited. One or more types selected from the group consisting of extracts: 1 part by mass, preferably 1 to 30 parts by mass of starch, more preferably 3 to 20 parts by mass, and particularly preferably 5 to 15 parts by mass. In addition, when converted into a native drug amount, the content of one or more selected from the group consisting of Magnolia officinalis and its extracts is higher than that of the group consisting of Magnolia officinalis and its extracts, from the viewpoint of suppressing the decrease in MMSC content. One or more types selected in the group shall be calculated as 1 part by mass based on the original drug conversion amount. The preferred starch system contains 0.01~10 parts by mass, the more preferred system contains 0.05~5 parts by mass, and the particularly preferred system contains 0.1~1 part by mass.

In the present invention, the "composition" can be in any form of solid, semi-solid, or liquid, and can be formed into commonly used pharmaceuticals, quasi-drugs, cosmetics, foods, etc. according to the purpose of use. shape. Specifically, it can be formed into, for example: tablets (including orally disintegrating tablets, chewable tablets, foaming tablets, dispersing tablets, dissolving tablets, oral tablets (including tablets, sublingual tablets, buccal tablets, adhesive tablets) Tablets, oral gels), capsules, granules (including foaming granules), powders and other solid preparations; oral liquids (including elixirs, suspensions, emulsions, lemons), syrups, oral Liquid preparations such as liquid preparations; semi-solid preparations such as oral gels and oral semi-solid preparations, etc., the 17th edition revised the dosage forms described in the General Principles of Preparations of the Japanese Pharmacopoeia.

In the present invention, from the viewpoint of suppressing the decrease in MMSC content, a solid composition is preferred, and a dosage form selected from the group consisting of tablets, capsules, granules, and powders is more preferred, and a dosage form selected from the group consisting of tablets is particularly preferred. and granules.

In the composition of the present invention, in addition to the above-mentioned ingredients, the above-mentioned shape and dosage form can be combined according to known methods in the pharmaceutical field, quasi-pharmaceutical field, cosmetic field, food field, etc., such as the 17th edition of the Japanese Pharmacopoeia revised preparation. Manufacture according to the method described in General Principles, etc.

In addition to the above-mentioned ingredients, the composition of the present invention can also be formulated with carriers (excipients, binding agents, disintegrants, lubricants, colorants, One or more of the following: flavoring agents, coating agents, etc.).

Examples of excipients include lactose, crystalline cellulose, sucrose, mannitol, light anhydrous silicic acid, and the like. Examples of the binding agent include hydroxypropyl methylcellulose, hydroxypropyl cellulose, gelatin, polyvinylpyrrolidone, polyvinyl alcohol, polytriglycerol, and the like. Examples of the disintegrating agent include carboxymethylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, crosprovidone, low-substitution hydroxypropylcellulose, and the like. Examples of lubricants include magnesium stearate, talc, and the like. Examples of the coloring agent include tar dye, ferric oxide, and the like. Examples of flavoring agents include stevia, aspartame, and the like. Examples of coating agents include carboxymethylethylcellulose, cellulose acetate phthalate, methacrylic acid copolymer S, methacrylic acid copolymer L, methacrylic acid copolymer LD, and hydroxypropylmethylcellulose phthalate. acid ester, hydroxypropyl methylcellulose acetate succinate and other film-forming polymers. In addition, when forming a film, plasticizers such as triethyl citrate, glyceryl triacetate, and polyethylene glycol can also be prepared; talc, titanium oxide, yellow ferric oxide, ferric oxide, and legal pigments , light anhydrous silicic acid, hydrated silica and other powders. In the present invention, one type of these may be blended, or two or more types may be blended appropriately in combination.

Furthermore, in addition to the above-mentioned components, other medicinal ingredients may also be blended in the composition of the present invention. There are no special restrictions on the active ingredients. It is sufficient to make an appropriate selection based on the diseases and symptoms of the applicable ingredients. For example, local anesthetics, digestive agents (cholagogues), digestive enzymes, and gastric mucosal repair. agents (mucosal protective ingredients), crude drug ingredients, antacids, etc. These can be prepared individually or in combination of two or more.

Examples of local anesthetics include ethyl aminobenzoate, oxethazaine, and the like. Examples of digestive agents (cholagogues) include ursodeoxycholic acid (Ursodeoxycholic acid), animal bile (bear bile, ox bile), and the like. Examples of the digestive enzyme system include starch-digesting enzymes (biodiastase, taka diastase), fat-digesting enzymes (lipase), and the like. Examples of gastric mucosal repair agents (mucosal protective ingredients) include sodium copper chlorophyllin, potassium copper chlorophyllin, aluminum ureacystin (ALDIOXA), sucralfate, cetraxate hydrochloride, and sofazone (sofalcone), gefarnate, trimebutine maleate, sodium azulenesulfonate, etc. Examples of herbal medicine ingredients include: Uncaria catechu, Fennel fruit, aloe vera, cumin, turmeric, ebony plum, ebony root, Corydalis corydalis, Yanmingcao, Scutellaria baicalensis, Phellodendri, coptis, processed garlic, Curcuma zedoary, Agastache, calamus root (calamus) root), dried ginger (processed ginger), licorice, immature orange, sophora flavescens, cinnamon, cassia, gentian, geranium, red ginseng, evodia, pepper, gallnut, fangchi, condurango , mountain plants, pepper, kaempferol, perilla seed, peony, amomum villosum, ginger, cardamom, green bark, catalpa bud, calamus root, daylily, atractylodes, anise, rhubarb, bamboo ginseng, cloves, tangerine peel , pepper, orange peel, bitter tree, nutmeg, ginseng, peppermint, water mint, peppermint, atractylodes, hops, nux vomica, nightweed leaves, alpinia oxyphylla, bayberry bark, gentian, and alpinia and other crude drugs or their extracts. Examples of the antacid system include: proton pump inhibitors such as Omeprazole, Lansoprazole, and Rabeprazole sodium; Cimetidine, Ranide Hydrochloride H2 receptor antagonists such as Ranitidine Hydrochloride and Famotidine; dry aluminum hydroxide gel, magnesium aluminum silicate, magnesium aluminum metasilicate, magnesium silicate, synthetic aluminum silicate, synthetic Hydrotalcite, magnesium oxide, aluminum magnesium hydroxide, aluminum hydroxide gel, aluminum hydroxide‧sodium bicarbonate co-precipitation product, aluminum hydroxide‧magnesium carbonate mixed dry gel, aluminum hydroxide‧magnesium carbonate‧calcium carbonate co-precipitation product Sediment products, magnesium hydroxide, sodium bicarbonate, magnesium carbonate, precipitated calcium carbonate, magnesium aluminum metasilicate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate and other inorganic salts; cuttlebone, Cassia, oyster, aminoacetic acid , dihydroxyaluminum acetate, etc. In the present invention, one type of these may be blended, or two or more types may be blended appropriately in combination.

The composition of the present invention can be used as pharmaceuticals, quasi-pharmaceuticals, cosmetics, food, etc. The purpose of its use is not particularly limited. However, because it contains MMSC that has a protective effect on the digestive tract mucosa, it is preferably used as a medicine. More preferably, it is used as a medicine for improving subjective and other symptoms such as gastric ulcer, duodenal ulcer, and gastritis, and for improving liver function of chronic liver disease. Furthermore, the gastrointestinal medicine is more specifically preferably used as a medicine for: stomach discomfort, weak stomach, stomach irritation, stomach pain, overeating, overdrinking, heartburn, belching (hiccup, gastric hiccup, hangover and drunkenness) Hiccup, vomiting, nausea), vomiting, loss of appetite, indigestion, hyperacidity, hiccups, nausea, digestion promotion, stomach/abdominal bloating, and stomach heaviness are effective. ‧Effective gastrointestinal medicine.

The method of administration of the composition of the present invention is not particularly limited. Examples include oral administration and parenteral administration. The method can be appropriately selected according to the purpose of use of the composition. From the perspective of the protective effect of the digestive tract mucosa of MMSC, it is relatively Best for oral administration. In addition, there are no special restrictions on the usage or dosage of the composition, as long as it is appropriately selected and determined in accordance with the purpose of use of the composition, the method of administration, the dosage form of the composition, etc.

Furthermore, the present invention also relates to a method for stabilizing methionine chloride in the composition (preferably, a method for inhibiting a decrease in the content of methionine chloride in the composition), which includes: making the following Ingredients (A):

(A) methionine chloride; and

The following ingredients (B);

(B) One or more species selected from the group consisting of Magnolia officinalis and its extracts;

steps contained in the same composition.

In the invention of this aspect, the order of the step of containing component (A) and the step of containing component (B) is not particularly limited as long as it can directly or indirectly produce a product containing component (A) and (B). The composition can be.

In addition, in this aspect of the invention, the meanings of various terms, the blending amounts of each component, etc. are the same as those described in the above "composition".

This specification is not limited to these, but may disclose the following embodiments, for example.

[1A] A composition containing the following components (A) and (B):

(A) Methionine chloride;

(B) One or more species selected from the group consisting of Magnolia officinalis and its extracts.

[2A] The composition according to [1A], wherein the extract of Magnolia officinalis uses a solvent selected from the group consisting of water, lower monohydric alcohol and a mixed liquid thereof as the extraction solvent.

[3A] The composition according to [1A] or [2A], further containing at least one selected from the group consisting of the following components (C) and (D);

(C) One or more species selected from the group consisting of perilla leaves and their extracts;

(D) Starches.

[4A] The composition according to [3A], wherein the perilla leaf extract uses a solvent selected from the group consisting of water, lower monohydric alcohol, and a mixed solution thereof as the extraction solvent.

[5A] The composition according to [3A] or [4A], wherein the starch is selected from starch, hydroxy C1-C6 alkyl ether of starch, carboxy C1-C6 alkyl ether of starch, and salts thereof Select one or more types from the group formed.

[6A] The composition according to any one of [3A] to [5A], wherein the starch is selected from the group consisting of starch, hydroxypropyl starch, carboxymethyl starch, and salts thereof More than 1 species.

[7A] The composition described in any one of [1A] to [6A] is a solid composition.

[8A] The composition according to any one of [1A] to [7A], which is a dosage form selected from the group consisting of tablets, capsules, granules and powders.

[9A] The composition described in any one of [1A] to [8A] is a gastrointestinal drug.

[1B] A method for stabilizing methionine chloride in a composition, which includes:

Make the following ingredients (A):

(A) Methionine chloride;

With the following ingredients (B):

(B) One or more species selected from the group consisting of Magnolia officinalis and its extracts;

steps contained in the same composition.

[2B] The method according to [1B], wherein the extract of Magnolia officinalis uses a solvent selected from the group consisting of water, lower monohydric alcohols, and mixed liquids thereof as the extraction solvent.

[3B] The method according to [1B] or [2B], further comprising at least one selected from the group consisting of the following components (C) and (D):

(C) One or more species selected from the group consisting of perilla leaves and their extracts;

(D) Starch;

contained in the same composition.

[4B] The method according to [3B], wherein the perilla leaf extract uses a solvent selected from the group consisting of water, lower monohydric alcohol, and a mixed solution thereof as the extraction solvent.

[5B] The method according to [3B] or [4B], wherein the starch is obtained from starch, hydroxy C1-C6 alkyl ether of starch, carboxy C1-C6 alkyl ether of starch, and salts thereof. 1 or more types selected from the group.

[6B] The method according to any one of [3B] to [5B], wherein the starch is selected from the group consisting of starch, hydroxypropyl starch, carboxymethyl starch, and salts thereof More than 1 species.

[7B] The method according to any one of [1B] to [6B], wherein the composition is a solid composition.

[8B] The method according to any one of [1B] to [7B], wherein the dosage form of the composition is a dosage form selected from the group consisting of tablets, capsules, granules, and powders.

[9B] The method according to any one of [1B] to [8B], wherein the composition is a gastrointestinal drug.

[Example]

The following examples are given to describe the present invention in detail. However, the present invention is not limited only to these examples.

[Test Example 1] Stability test

After preparing the samples 1 to 3 shown below respectively, store them at 80°C for 1 day. Use an HPLC device to quantify the MMSC content in the samples before and after storage according to the internal standard method. From the measured values obtained, the MMSC content of each sample after being stored at 80°C for 1 day was evaluated based on the relative value (residual rate: %) when the content at the start of the test was set to 100%.

The results are shown in Table 1.

[Sample 1]

1 g of MMSC (MMSC: Yonezawa Riko Industrial Co., Ltd.) was put into a plastic container and used as sample 1 as it was.

[Sample 2]

Mix 1 g of MMSC (MMSC: Yonezawa Riko Industrial Co., Ltd.) and 1 g of Magnolia officinalis dry extract (Magnolia officinalis dry extract: Nippon Powder Pharmaceutical Co., Ltd.), and put the obtained mixture into a plastic container. , as sample 2.

[Sample 3]

1 g of MMSC (MMSC: Yonezawa Riko Industrial Co., Ltd.), 1 g of Magnolia officinalis dry extract (Magnolia officinalis dry extract: Nippon Powder Pharmaceutical Co., Ltd.), and perilla leaf dry extract (Perilla leaf dry extract - Q: 1 g of Nippon Powder Pharmaceutical Co., Ltd. was mixed, and the obtained mixture was put into a plastic container to prepare Sample 3.

From the results recorded in Table 1, it can be seen that the MMSC survival rate of sample 1 (only MMSC) after being stored at 80°C for 1 day was 91%. In contrast, the MMSC survival rate of sample 2 (a mixture of MMSC and Magnolia officinalis dried extract) The survival rate was increased to 94%, and the decrease in MMSC content was suppressed.

In addition, it was found that the MMSC residual rate of sample 3 (a mixture of MMSC, Magnolia officinalis dried extract, and perilla leaf dried extract) was improved to 100%, and the decrease in MMSC content was further suppressed.

It is known from the above test results that at least one selected from the group consisting of Magnolia officinalis and its extracts has the effect of inhibiting the decrease in MMSC content. Furthermore, it was found that in addition to one or more types selected from the group consisting of MMSC, Magnolia officinalis and their extracts, by further allowing one or more types selected from the group consisting of perilla leaves and their extracts to coexist , can further inhibit the decrease in MMSC content.

[Test Example 2] Stability Test 2

After preparing Sample 4 shown below, the test was carried out in the same manner as in Test Example 1.

The results are shown in Table 2.

[Sample 4]

1 g of MMSC (MMSC: Yonezawa Riko Industrial Co., Ltd.), 1 g of magnolia bark dry extract (Magnolia officinalis dry extract: Nippon Powder Pharmaceutical Co., Ltd.), and corn starch (maize starch ST-C: Nidyo Chemical Co., Ltd. (stock)) was mixed, and the obtained mixture was put into a plastic container to prepare Sample 4.

From the results shown in Table 2, it can be seen that sample 4 (a mixture of MMSC, Magnolia officinalis dry extract, and corn starch), like sample 3 of Test Example 1, has an extremely high MMSC residual rate of 99%.

From the above test results, it is known that in addition to selecting one or more types from the group consisting of MMSC, Magnolia officinalis and their extracts, by further coexisting starch, the decrease in MMSC content can be further suppressed.

[Manufacturing Example 1]

Coated tablets containing the following ingredients per 1 tablet (700mg) are manufactured according to usual methods. The 100 coated tablets produced were stored in a plastic container (10K standard bottle made of polyethylene).

Methionine chloride 25mg

Scopolamine extract 3 times powder 15mg

When powdered, 4.7mg

Dried perilla leaf extract 3.3mg (converted amount of native drug: 30mg)

Magnolia officinalis dry extract 2.5mg (converted amount of native medicine: 30mg)

Bioamylase 2000 4mg

Lipase AP(lipase)12 2.5mg

Sodium bicarbonate 100mg

Precipitated calcium carbonate 223mg

Magnesium hydroxide 35mg

Hydroxypropylcellulose

hardened oil

carboxymethylcellulose calcium

corn starch

Magnesium stearate

Glyceryl stearate

Polyethylene glycol stearate

Shellac

Talc

cinnamon

Polyvinyl alcohol (partially saponified product)

D-Mannitol

cellulose

Silicon dioxide

1-menthol

[Manufacturing Example 2]

Coated tablets containing the following ingredients per 1 tablet (680 mg) are manufactured according to usual methods. The 200 coated tablets produced were stored in a plastic container (12K standard bottle made of polyethylene).

Methionine chloride 25mg

Scopolamine extract 3 times powder 15mg

When powdered, 4.7mg

Dried perilla leaf extract 3.3mg (converted amount of native drug: 30mg)

Magnolia officinalis dry extract 2.5mg (converted amount of native medicine: 30mg)

Bioamylase 2000 4mg

Lipase AP12 2.5mg

Sodium bicarbonate 100mg

Precipitated calcium carbonate 223mg

Magnesium hydroxide 35mg

Hydroxypropyl cellulose

hardened oil

carboxymethylcellulose calcium

corn starch

Magnesium stearate

Glyceryl stearate

Polyethylene glycol stearate

Shellac

Talc

cinnamon

Polyvinyl alcohol (partially saponified product)

cellulose

Silicon dioxide

1-menthol

[Manufacturing Example 3]

Coated tablets containing the following ingredients per 1 tablet (690 mg) are manufactured according to usual methods. The 300 coated tablets produced were stored in a plastic container (14K standard bottle made of polyethylene).

Methionine chloride 25mg

Scopolamine extract 3 times powder 15mg

When powdered, 4.7mg

Dried perilla leaf extract 3.3mg (converted amount of native drug: 30mg)

Magnolia officinalis dry extract 2.5mg (converted amount of native medicine: 30mg)

Bioamylase 2000 4mg

Lipase AP12 2.5mg

Sodium bicarbonate 100mg

Precipitated calcium carbonate 223mg

Magnesium hydroxide 35mg

Hydroxypropyl cellulose

hardened oil

carboxymethyl cellulose calcium

corn starch

Magnesium stearate

Glyceryl stearate

Polyethylene glycol stearate

Shellac

Talc

cinnamon

Polyvinyl alcohol (partially saponified product)

Reduced maltose syrup

cellulose

Silicon dioxide

1-menthol

[Manufacturing Example 4]

According to the usual method, each package (1300mg) of granules containing the following ingredients is produced, and then packaged in aluminum pillows.

Methionine chloride 50mg

Scopolamine extract 3 times powder 30mg

When the medicine is powdered 9.3mg

Dried perilla leaf extract 6.6mg (original drug conversion amount 60mg)

Magnolia officinalis dried extract 5mg (original drug conversion amount 60mg)

Bioamylase 2000 8mg

Lipase AP12 5mg

Sodium bicarbonate 200mg

Precipitated calcium carbonate 447mg

Magnesium hydroxide 70mg

hardened oil

Hydroxypropyl cellulose

D-mannitol

carboxymethylcellulose calcium

Calcium lactate

Sucralose

1-menthol

Silicon dioxide

spices

corn starch

(industrial availability)

According to the present invention, it is possible to provide a composition with good quality and stability in which the content of methionine chloride is suppressed and the stability is improved, and can be used in the pharmaceutical industry and the pharmaceutical industry.

Claims (5)

A composition containing the following components (A) and (B) in a solid state: (A) methionine chloride; (B) selected from the group consisting of Magnolia officinalis and its extracts 1 or more types (excluding compositions containing Magnolia officinalis and cinnamon extracts and methionine chloride, fig and lipase that promote the activity and performance of intestinal digestive enzymes). The composition of claim 1, which further contains the following component (C): (C) One or more types selected from the group consisting of perilla leaves and their extracts. The composition of claim 1, which further contains the following component (D): (D) starch. The composition of claim 2 further contains the following component (D): (D) starch. The composition of any one of claims 1 to 4 is in a dosage form selected from the group consisting of tablets, capsules, granules and powders.