JP6823622B2 - Pharmaceutical composition containing crude drugs (land) - Google Patents

Description

The present invention relates to a crude drug-containing pharmaceutical composition, and a storage stabilizer and a method for stabilizing the crude drug-containing pharmaceutical composition.

Crude drugs such as Phellodendron amur and licorice have various pharmacological actions and are therefore widely used as components of pharmaceutical products. However, since components having various properties are present in crude drugs, the storage stability of the pharmaceutical composition containing the crude drug or the like tends to be a problem, and the development of a technique for improving the storage stability is required. Has been done. In particular, pharmaceutical products should be stored, stored, transported, etc. under temperature-controlled conditions (at least 30 ° C or lower, so-called room temperature), but the temperature is not always sufficiently controlled in the hands of consumers. Due to recent climate change and the tendency of power saving due to the world, it is possible that the product is stored at a high temperature of well over 30 ° C. Therefore, it is extremely important to ensure storage stability under high temperature conditions.

As a problem of storage stability in a pharmaceutical composition containing a crude drug or the like, there is a precipitation in a liquid pharmaceutical composition due to a low-solubility component contained in a large amount in the crude drug, and such a problem can be solved. A technique for blending a solubilizer is being studied. For example, Patent Document 1 describes that a crude drug extract is blended with polyoxyethylene cured castor oil and a polyoxyethylene polyoxypropylene condensate. Further, Patent Document 2 describes a solubilized liquid composition in which a polyglycerin fatty acid ester and a polyoxyethylene nonionic surfactant are blended in a specific ratio in addition to a crude drug extract and an oil component. ..

By the way, loxoprofen is a kind of non-steroidal anti-inflammatory drug (NSAID) also known as an active ingredient of loxonin (registered trademark) (Non-Patent Document 1), and has osteoarthritis, muscle pain, and swelling after trauma. It is used as an active ingredient of external preparations such as gels, poultices and tapes, which have anti-inflammatory and analgesic effects on diseases and symptoms such as pain (Non-Patent Document 2).
However, it has not been known at all how loxoprofen affects the storage stability of pharmaceutical compositions containing crude drugs and the like.

Special Fair 5-9408 Gazette JP-A-2002-128703

16th Amendment Japanese Pharmacopoeia Manual Hirokawa Shoten Co., Ltd. C-5359-5364 Loxonin® Gel 1% Pharmaceutical Interview Form Daiichi Sankyo Co., Ltd. October 2010 Revised (3rd Edition)

An object of the present invention is to provide a crude drug-containing pharmaceutical composition having excellent storage stability, and a storage stabilizer and a stabilization method for the crude drug-containing pharmaceutical composition.

Therefore, as a result of diligent studies to solve the above problems, the present inventors have conducted diligent studies, and found that crude drugs selected from Phellodendron amurensis, licorice, horse chestnut seeds and horse chestnut seeds and extracts thereof, or glycyrrhetinic acid, and loxoprofene or a salt thereof. The present invention has been completed by finding that a pharmaceutical composition having excellent storage stability can be obtained by containing the above-mentioned substance.

That is, the present invention has the following components (A) and (B).
(A) One or more selected from the following components (A-1) to (A-6) (A-1) Horse chestnut or its extract (A-2) Licorice or its extract (A-3) Glycyrrhetinic acid Or its salt (A-4) licorice or its extract (A-5) horse chestnut seed or its extract (A-6) licorice or its extract (B) a pharmaceutical composition containing loxoprofen or its salt It is to provide.

The present invention also relates to horse chestnut or its extract, licorice or its extract, glycyrrhetinic acid or its salt, horse chestnut or its extract, horse chestnut seed or its extract, or horse chestnut or its extract, which contains loxoprofen or its salt. It provides a storage stabilizer for a pharmaceutical composition containing the extract.

The present invention also relates to horse chestnut or its extract, licorice or its extract, glycyrrhetinic acid or its salt, horse chestnut or its extract, horse chestnut seed or its extract, or horse chestnut or its extract, which contains loxoprofen or its salt. It provides a method for stabilizing a pharmaceutical composition containing the extract.

According to the present invention, it is possible to provide a pharmaceutical composition having excellent storage stability while containing a crude drug or the like.

<Ingredient (A-1)>
"Oubaku" (Huang Kashiwa) means the bark of the yellowfin (Phellodendron amurense Ruprecht or Phellodendron chinense Schneider (Rutaceae)) excluding the periderm, as described in the 16th revised Japanese Pharmacopoeia. The morphology of Phellodendron amur can be adjusted as needed, and it can be cut or crushed into small pieces or lumps, or crushed into powder. For example, "Phellodendron amur powder" obtained by powdering Phellodendron amur is also used in the present invention. Can be done. Further, in consideration of convenience of handling at the time of manufacturing the pharmaceutical composition, a product obtained by subjecting Phellodendron amur to some sort of extraction treatment (hereinafter, referred to as "extract of Phellodendron amur") may be used.
The above-mentioned "extract of Phellodendron amurensis" includes those subjected to processing treatments such as heating, drying and pulverization in addition to the extraction treatment. Specifically, after making Phellodendron amur into an appropriate size as needed, a solution leached by adding an appropriate leachate (extraction solvent), a solution obtained by concentrating the leachate (soft extract, tincture, etc.), and further, these are added. Dried ones (dried extract, etc.) are also included in the "extract of Phellodendron amur" of the present invention.
In the present invention, as the Phellodendron amur or its extract, the Phellodendron amur soft extract and the Phellodendron amurensis and Phellodendron amur powder described in the 16th revised Japanese Pharmacopoeia are preferable, and the Phellodendron amurensis soft extract is particularly preferable.

The method for producing the extract of Oubaku is not particularly limited. For example, the description in the section of "extract", "immersion / decoction", "tincture", "flow extract" in the 16th revised Japanese Pharmacopoeia General Regulations for Formulation, etc. , Can be produced with reference to known methods for producing plant extracts. Specifically, for example, Phellodendron amur can be produced by cutting, heating, drying, pulverizing, etc., if necessary, and then adding an appropriate extraction solvent for extraction. The obtained extract may be further concentrated, dried or the like, if necessary.

Examples of the 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-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; benzene, toluene and the like Aromatic hydrocarbons; dimethylformamide; dimethylsulfohoxide; water (including hot water) and the like. Each of these may be used alone, or two or more thereof may be used in combination. In the present invention, water, ethanol, or a water / ethanol mixed solution is preferable.
The extraction operation is not particularly limited, and a known method used for the extraction operation from a plant can be adopted. Specifically, for example, immersion in an extraction solvent (cold immersion, warm immersion, percolation, etc.), super Extraction using a critical fluid or a subcritical fluid can be mentioned. In addition, in order to improve the extraction efficiency, it may be homogenized with stirring or in an extraction solvent.
The extraction temperature is not particularly limited and varies depending on the extraction solvent used, the extraction operation and the like, but it is preferably a temperature from about 5 ° C. to the boiling point of the extraction solvent or less.
The extraction time is not particularly limited and varies depending on the extraction solvent used, the extraction operation and the like, but is preferably about 1 hour to 14 days.

In the present invention, a commercially available product can be used as the Phellodendron amur or its extract, and specific commercial products include, for example, Phellodendron amurensis soft extract, dried Phellodendron amur extract (all manufactured by Nippon Powder Chemicals Co., Ltd.) and the like. Be done.

The content of Phellodendron amurensis or an extract thereof in the pharmaceutical composition of the present invention is not particularly limited and may be determined by appropriate examination. In the present invention, Phellodendron amurensis or an extract thereof is preferably contained in an amount equivalent to that of a crude drug in an amount of 0.01 to 10% by mass, more preferably 0.05 to 8% by mass, based on the total mass of the pharmaceutical composition. It is preferable, and the one containing 0.1 to 5% by mass is particularly preferable.

The content ratio of Phellodendron amurensis or its extract contained in the pharmaceutical composition of the present invention to loxoprofen or a salt thereof is not particularly limited, but from the viewpoint of storage stability, loxoprofen or a salt thereof is converted into loxoprofen sodium anhydride. It is preferable that Phellodendron amurensis or its extract is contained in an amount of 0.01 to 10 parts by mass, more preferably 0.05 to 8 parts by mass, and 0.1 to 5 parts by mass with respect to 1 part by mass. Part-containing ones are particularly preferable.

<Ingredient (A-2)>
"Licorice" (licorice) means the roots and strons of Glycyrrhiza uralensis Fischer or Glycyrrhiza glabra Linne (Leguminosae), and is a concept that includes those excluding the peripheral skin (peeling licorice) (16th revision). Japanese pharmacy). The form of licorice can be adjusted as needed, and it can be cut or crushed into small pieces or lumps, or crushed into powder. For example, "licorice powder" obtained by powdering licorice is also used in the present invention. Can be done. Further, in consideration of convenience of handling at the time of manufacturing the pharmaceutical composition, licorice that has undergone some extraction treatment (hereinafter, referred to as "licorice extract") may be used.
The above-mentioned "licorice extract" includes those subjected to processing treatments such as heating, drying and pulverization in addition to the extraction treatment. Specifically, after licorice is made into an appropriate size as needed, a liquid leached by adding an appropriate leachate (extraction solvent), a liquid obtained by concentrating the leachate (soft extract, tincture, etc.), and these are further added. Dried ones (dried extract, etc.) are also included in the "licorice extract" of the present invention.
Further, in the present invention, glycyrrhizic acid, which is a component of licorice, or a salt thereof may be used as the licorice extract. Examples of the salt of glycyrrhizic acid include dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, disodium glycyrrhizinate, and trisodium glycyrrhizinate.
In the present invention, as the licorice or its extract, dipotassium glycyrrhizinate and licorice, licorice powder, licorice extract, and licorice crude extract described in the 16th revised Japanese Pharmacy are preferable, and licorice is particularly preferable.

The method for producing the licorice extract is not particularly limited, and for example, it can be produced by the same method as the above-mentioned method for producing the extract of Phellodendron amur.

In the present invention, a commercially available product can be used as the licorice or its extract, and specific commercially available products include, for example, (station) licorice extract, (station) licorice powder, and (station) licorice crude extract (the above, (Manufactured by Nippon Powder Chemicals Co., Ltd.) and the like.

The content of licorice or its extract in the pharmaceutical composition of the present invention is not particularly limited and may be determined by appropriate examination. In the present invention, licorice or an extract thereof is preferably contained in an amount equivalent to a crude drug of 0.01 to 10% by mass with respect to the total mass of the pharmaceutical composition, and more preferably 0.05 to 8% by mass. It is preferable, and the one containing 0.1 to 5% by mass is particularly preferable.

The content ratio of licorice or its extract contained in the pharmaceutical composition of the present invention to loxoprofen or a salt thereof is not particularly limited, but from the viewpoint of storage stability, loxoprofen or a salt thereof is converted into loxoprofen sodium anhydride. It is preferable that licorice or an extract thereof is contained in an amount of 0.01 to 10 parts by mass, more preferably 0.05 to 8 parts by mass, and 0.1 to 5 parts by mass with respect to 1 part by mass. Part-containing ones are particularly preferable.

<Ingredient (A-3)>
"Glycyrrhizic acid" is a hydrolyzate of the component (glycyrrhizinic acid) of the above-mentioned "licorice", and in the present invention, in addition to glycyrrhetinic acid itself, a pharmaceutically acceptable salt thereof, glycyrrhetinic acid and its pharmaceutically acceptable salt. A solvate of an acceptable salt with water, alcohol, etc. is also included. These are known compounds and can be produced by known methods, or commercially available compounds can be used.
In the present invention, glycyrrhetinic acid described in the Japanese Pharmacopoeia Non-Pharmaceutical Standard 2002 is preferable.

The content of glycyrrhetinic acid or a salt thereof in the pharmaceutical composition of the present invention is not particularly limited and may be determined by appropriate examination. In the present invention, glycyrrhetinic acid or a salt thereof is preferably contained in an amount of 0.005 to 10% by mass, preferably 0.01 to 8% by mass, based on the total mass of the pharmaceutical composition in terms of free form of glycyrrhetinic acid. Is more preferable, and those containing 0.05 to 5% by mass are particularly preferable.

The content ratio of glycyrrhetinic acid or a salt thereof contained in the pharmaceutical composition of the present invention to loxoprofen or a salt thereof is not particularly limited, but from the viewpoint of storage stability, loxoprofen or a salt thereof is converted into loxoprofen sodium anhydride. It is preferable that glycyrrhetinic acid or a salt thereof is contained in an amount of 0.005 to 10 parts by mass, more preferably 0.01 to 8 parts by mass, and 0.05 to 5 parts by mass with respect to 1 part by mass. Those containing are particularly preferable.

<Ingredient (A-4)>
"Sansho" (sansho) means the mature pericarp of sansho (Zanthoxylum piperitum De Candolle (Rutaceae)) as described in the 16th revised Japanese Pharmacopoeia. The form of Japanese pepper can be adjusted as needed, and it can be cut or crushed into small pieces or lumps, or crushed into powder. For example, "Japanese pepper powder" obtained by powdering Japanese pepper is also the present invention. Can be used for. Further, in consideration of convenience of handling at the time of manufacturing the pharmaceutical composition, a sansho that has been subjected to some extraction treatment (hereinafter, referred to as "sansho extract") may be used.
The above-mentioned "Japanese pepper extract" includes those subjected to processing treatments such as heating, drying, and pulverization in addition to the extraction treatment. Specifically, a liquid leached by adding an appropriate leachate (extraction solvent) after making the sansho into an appropriate size as needed, a liquid obtained by concentrating the leachate (soft extract, tincture, etc.), and these. The dried product (dried extract, etc.) is also included in the "extract of tincture" of the present invention.
In the present invention, as the Japanese pepper or its extract, the Japanese pepper soft extract, the Japanese pepper and the Japanese pepper powder described in the 16th revised Japanese Pharmacopoeia are preferable, and the Japanese pepper soft extract is particularly preferable.

The method for producing the extract of Japanese pepper is not particularly limited, and for example, it can be produced by the same method as the method for producing the extract of Phellodendron amur.

In the present invention, a commercially available product can be used as the Japanese pepper or an extract thereof, and specific commercial products include, for example, Japanese pepper soft extract (manufactured by Alps Pharmaceutical Industry Co., Ltd.), (bureau) Japanese pepper powder (bureau). (Manufactured by Nippon Powder Chemical Co., Ltd.) and the like.

The content of Japanese pepper or an extract thereof in the pharmaceutical composition of the present invention is not particularly limited and may be determined by appropriate examination. In the present invention, Japanese pepper or an extract thereof is preferably contained in an amount equivalent to a crude drug of 0.01 to 10% by mass, preferably 0.05 to 8% by mass, based on the total mass of the pharmaceutical composition. More preferably, those containing 0.1 to 5% by mass are particularly preferable.

The content ratio of loxoprofen or its salt to the extract of sansho or its extract contained in the pharmaceutical composition of the present invention is not particularly limited, but from the viewpoint of storage stability, loxoprofen or its salt is converted into loxoprofen sodium anhydride. In 1 part by mass of loxoprofen, 0.01 to 10 parts by mass of loxoprofen or its extract is preferably contained, more preferably 0.05 to 8 parts by mass, and 0.1 to 1 part by mass. Those containing 5 parts by mass are particularly preferable.

<Ingredient (A-5)>
"Horse-chestnut seeds" are seeds of horse-chestnut (Aesculus hippocastanum Linne (Hippocastanaceae)). Horse chestnut seeds can be adjusted in morphology as needed and can be cut or crushed into small pieces, lumps, or crushed into powder. In addition, in consideration of convenience of handling during production of the pharmaceutical composition, horse chestnut seeds subjected to some extraction treatment (hereinafter, referred to as "extract of horse chestnut seeds") may be used.
The above-mentioned "Aesculus hippocastanum seed extract" includes those subjected to processing treatments such as heating, drying, and crushing in addition to the extraction treatment. Specifically, a liquid obtained by adding an appropriate leachate (extraction solvent) after making horse chestnut seeds into an appropriate size as necessary, a liquid obtained by concentrating the leachate (soft extract, tincture, etc.), and further. Dried products (dried extract, etc.) are also included in the "extract of horse chestnut seeds" of the present invention.
In the present invention, as the horse chestnut seed or its extract, the horse chestnut seed extract described in the Japanese Pharmacopoeia Non-Pharmaceutical Standard 2002 is preferable.

The method for producing the horse chestnut seed extract is not particularly limited, and for example, it can be produced by the same method as the above-mentioned method for producing the extract of Phellodendron amurensis.

In the present invention, a commercially available product can be used as the horse chestnut seed or an extract thereof, and specific commercial products include, for example, Falcolex Maronnier B (manufactured by Ichimaru Falcos Co., Ltd.).

The content of horse chestnut seeds or an extract thereof in the pharmaceutical composition of the present invention is not particularly limited and may be determined by appropriate examination. In the present invention, the horse chestnut seed or its extract is preferably contained in an amount of 0.01 to 10% by mass, preferably 0.05 to 8.5% by mass, based on the total mass of the pharmaceutical composition in terms of crude drug. The one containing 0.1 to 6.5% by mass is particularly preferable.

The content ratio of horse chestnut seed or its extract contained in the pharmaceutical composition of the present invention to loxoprofen or a salt thereof is not particularly limited, but from the viewpoint of storage stability, loxoprofen or a salt thereof is used as loxoprofen sodium anhydride. It is preferable that the horse chestnut seed or its extract is contained in an amount of 0.01 to 10 parts by mass, more preferably 0.05 to 8.5 parts by mass, based on 1 part by mass in terms of crude drug. Those containing 0.1 to 6.5 parts by mass are particularly preferable.

<Ingredient (A-6)>
"Peppers" (Peppers) means the fruits of Peppers (Capsicum annuum Linne (Solanaceae)) as described in the 16th revised Japanese Pharmacopoeia. The morphology of the pepper can be adjusted as needed, and it can be cut or crushed into small pieces or lumps, or crushed into powder. For example, "pepper powder" obtained by powdering pepper is also used in the present invention. Can be done. Further, in consideration of convenience of handling at the time of manufacturing the pharmaceutical composition, a pepper which has been subjected to some extraction treatment (hereinafter, referred to as “pepper extract”) may be used.
The above-mentioned "pepper extract" includes those subjected to processing treatments such as heating, drying, and pulverization in addition to the extraction treatment. Specifically, after making the pepper into an appropriate size as needed, a liquid leached by adding an appropriate leachate (extraction solvent), a liquid obtained by concentrating the leachate (soft extract, tincture, etc.), and further, these are added. Dried ones (dried extract, etc.) are also included in the "extract of pepper" of the present invention.
Further, in the present invention, as the extract of pepper, a known capsaicinoid which is a main component of pepper may be used. As the capsaicinoid, capsaicin and nonanoic acid vanillylamide are preferable.
In the present invention, as the pepper or its extract, soft pepper extract, capsaicin, vanillylamide nonanoic acid, and pepper, powder of pepper, and peppertinki described in the 16th revised Japanese Pharmacy are preferable, and soft pepper extract is particularly preferable.

The method for producing the extract of Phellodendron amur is not particularly limited, and for example, it can be produced by the same method as the method for producing the extract of Phellodendron amur.

In the present invention, a commercially available product can be used as the pepper or its extract, and specific commercially available products include, for example, pepper extract B, (bureau) pepper powder (all manufactured by Nippon Powder Chemicals Co., Ltd.) and the like. Can be mentioned.

The content of the pepper or its extract in the pharmaceutical composition of the present invention is not particularly limited and may be determined by appropriate examination. In the present invention, it is preferable that the pepper or its extract is contained in an amount equivalent to a crude drug of 0.01 to 15% by mass with respect to the total mass of the pharmaceutical composition, and more preferably 0.05 to 10% by mass. It is preferable, and the one containing 0.1 to 8% by mass is particularly preferable. When a capsaicinoid such as capsaicin or nonanoic acid vanillylamide is used as the pepper or its extract, it preferably contains 0.0001 to 1% by mass of the capsaicinoid with respect to the total mass of the pharmaceutical composition, 0.0005 to 0. The one containing 5.5% by mass is more preferable, the one containing 0.001 to 0.1% by mass is further preferable, and the one containing 0.005 to 0.02% by mass is particularly preferable.

The content ratio of loxoprofen or its extract contained in the pharmaceutical composition of the present invention to loxoprofen or a salt thereof is not particularly limited, but from the viewpoint of storage stability, loxoprofen or a salt thereof is converted into loxoprofen sodium anhydride. It is preferable that loxoprofen or an extract thereof is contained in an amount of 0.01 to 15 parts by mass, more preferably 0.05 to 10 parts by mass, and 0.1 to 8 parts by mass with respect to 1 part by mass. Part-containing ones are particularly preferable. When a capsaicinoid such as capsaicin or nonanoic acid vanillylamide is used as the capsicum or its extract, it contains 0.0001 to 1 part by mass of loxoprofen or a salt thereof in terms of 1 part by mass of loxoprofen sodium anhydride. Those containing 0.0005 to 0.5 parts by mass are more preferable, those containing 0.001 to 0.1 parts by mass are further preferable, and those containing 0.005 to 0.02 parts by mass are particularly preferable. preferable.

<Ingredient (B)>
In the present invention, "loxoprofen or a salt thereof" includes not only loxoprofen itself, but also a pharmaceutically acceptable salt of loxoprofen, and a solvate of loxoprofen or a pharmaceutically acceptable salt thereof and water, alcohol, or the like. Is done. These are known compounds and can be produced by known methods, or commercially available compounds can be used. In the present invention, as loxoprofen or a salt thereof, loxoprofen sodium hydrate (chemical name: Monosodium 2- [4-[(2-oxocyclopentyl) methyl] phenyl] propanoate dihydrate) is preferable.

The content of loxoprofen or a salt thereof in the pharmaceutical composition of the present invention is not particularly limited and may be appropriately examined and determined according to the effect of improving storage stability. However, from the viewpoint of storage stability, loxoprofen or a salt thereof may be used. With respect to the total mass of the pharmaceutical composition, 0.01 to 30% by mass, more preferably 0.1 to 25% by mass, still more preferably 0.5 to 20% by mass, 0.5 to 0.5% by mass in terms of loxoprofen sodium anhydride. It is more preferably 10% by mass, further preferably 0.5 to 5% by mass, and particularly preferably 0.5 to 3% by mass.

The pharmaceutical composition of the present invention can be produced, for example, by a known method described in the 16th revised Japanese Pharmacopoeia General Rules for Formulations and the like.
The dosage form is not particularly limited, and may be solid, semi-solid, or liquid, and may be a shape normally used in pharmaceutical products depending on the purpose of use. it can. For example, orally administered preparations (tablets, capsules, granules, powders, oral solutions, syrups, oral jelly, etc.), vaginal preparations (vaginal tablets, vaginal suppositories, etc.), skin, etc. Dosage forms such as preparations (solid preparations for external use, liquid preparations for external use, sprays, ointments, creams, gels, patches, etc.) may be used as described in the 16th revised General Rules for Preparations of the Japanese Pharmacy. Among these, a semi-solid or liquid preparation is preferable, and in particular, a dosage form selected from oral liquid preparations, syrup preparations, external liquid preparations, spray preparations, ointments, creams, gels and patches. Is preferable, and it is particularly preferable that the dosage form is selected from a liniment agent, a lotion agent, an external aerosol agent, a pump spray agent, an ointment agent, a cream agent, a gel agent, a tape agent and a poultice agent.

Further, the pharmaceutical composition of the present invention is preferably a semi-solid or liquid composition, and means a water-containing composition (meaning a semi-solid or liquid composition containing water, and more specifically, the composition. It means a composition containing 1% by mass or more, more preferably 5% by mass or more, and particularly preferably 10 to 80% by mass of water in the product). The semi-solid or liquid composition can be formulated as the semi-solid or liquid preparation. As specifically disclosed in the examples below, it has been confirmed that loxoprofen or a salt thereof suppresses precipitation, insoluble matter formation, separation, or coloring caused by crude drugs in a solution, and solubilizes the crude drugs. Is suggested.

Examples of the route for taking the pharmaceutical composition of the present invention include oral, transdermal, and parenteral such as transvaginal. In the present invention, parenteral is preferable, and transdermal administration is particularly preferable.

In the pharmaceutical composition of the present invention, as pharmaceutical components, drugs other than the above components, for example, analgesic components, anti-inflammatory components, antihistamine components, bactericidal components, astringent / protective components, blood circulation promoting components, local anesthetic components, antacids, etc. One or two selected from the group consisting of noscapines, bronchodilators, expectorants, hypnotic analgesics, vitamins, anti-inflammatory agents, gastromucosal protective agents, antacids, anticholinergic agents, crude drugs, Chinese herbal prescriptions, etc. It may contain more than a seed.

Examples of analgesic ingredients include aspirin, aspirin aluminum, acetaminophen, isopropylantipyrine, ibuprofen, etenzamid, sazapyrin, salicylamide, salicylic acid, ethylene glycol salicylate, glycol salicylate, sodium salicylate, methyl salicylate, thialamide hydrochloride, and lactylphenetidine. And so on.
Examples of the anti-inflammatory component include sodium guaiazulene sulfonate and the like.

Examples of the antihistamine component include azerastin hydrochloride, alimemazine tartrate, isotipendyl hydrochloride, iproheptin hydrochloride, evastin, epinastine hydrochloride, emedastin fumarate, oxatomide, carbinoxamine diphenyldisulfonate, and carbinoxamine. Maleate, clemastine fumarate, d-chlorphenylamine maleate, dl-chlorpheniramine maleate, ketotiphenfumarate, diphenhydramine hydrochloride, diphenhydramine phosphate, diphenylpyraline hydrochloride, diphenylpyraline Theocrulate, diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, cetilidine hydrochloride, triprolidine hydrochloride, tryperenamine hydrochloride, tonzilamine hydrochloride, hexofenazine, phenetazine hydrochloride, promethazine hydrochloride, promethazine methylenedi Examples thereof include salicylate, bepotastine besilate, homochlorcyclidine hydrochloride, mequitazine, metodilazine hydrochloride, mebuhydrolinnapadisylate and the like.

Examples of the bactericidal component include benzalkonium chloride and the like. Examples of the astringent / protective component include zinc oxide and the like. Examples of the blood circulation promoting component include tocopherol acetate, benzyl nicotinate, heparinoid, sodium polyethylene sulfonate and the like. Examples of the local anesthetic component include lidocaine, clove oil, belladonna extract and the like.

Antitussives include, for example, alloclamid hydrochloride, epradinone hydrochloride, carbetapentanetanate, cloperastine hydrochloride, cloperastin fendizoate, dibunato sodium, dimemorphan phosphate, tipepidin citrate, etc. Examples thereof include tipepidin hibenzate.

Examples of noscapines include noscapine hydrochloride, noscapine and the like.
Examples of the bronchodilator include trimetokinol hydrochloride, phenylephrine hydrochloride, methoxyphenamine hydrochloride and the like.

Examples of expectorants include ammonia / fennel, ammonium chloride, l-menthol and the like.

Examples of the hypnotic sedative include allylisopropylacetylurea and bromvalerylurea.
Examples of vitamins include vitamin B ₁ , vitamin B ₂ , vitamin B ₅ , vitamin B ₆ , vitamin B ₁₂ , vitamin C, hesperidin and derivatives thereof, and salts thereof (for example, thiamine, thiamine chloride hydrochloride, thiamine nitrification). Thing, disetiamine hydrochloride, setothiamine hydrochloride, flusultiamine, flusultiamine hydrochloride, octothiamine, sicothiamine, thiamine disulfide, bisibiamine, bisbenchamine, prosultiamine, benfothamine, riboflavin, riboflavin phosphate , Riboflavin butyrate, sodium riboflavine phosphate, pantenol, pantetin, sodium pantothenate, pyridoxin hydrochloride, pyridoxal phosphate, cyanocobalamine, mecobalamine, ascorbic acid, sodium ascorbate, calcium ascorbate, hesperidin, etc.).

Examples of the anti-inflammatory agent include seaprose, semi-alkali proteinase, serratiopeptidase, proctase, pronase, bromelain and the like.

Examples of the gastric mucosa protective agent include gefarnate, cetraxate hydrochloride, sofalcone, teprenone, methylmethionine sulfonium chloride and the like.
Antioxidants include aminoacetic acid, magnesium silicate, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate, magnesium hydroxide, magnesium hydroxide, aluminum hydroxide gel, and dry hydroxide. Aluminum gel, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / sodium hydrogen carbonate co-precipitated product, aluminum hydroxide / calcium carbonate / magnesium carbonate co-precipitated product, magnesium hydroxide, magnesium hydroxide / sulfuric acid Co-precipitated products of aluminum potassium, magnesium carbonate, sodium hydrogen carbonate, precipitated calcium carbonate, magnesium aluminometasilicate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, crow bones, stone determination, volley and the like.

Examples of the anticholinergic drug include oxyphencyclimine hydrochloride, dicyclamine hydrochloride, methixene hydrochloride, tipepidium bromide, methylbenactidium bromide, pirenzepine hydrochloride, isopropamide iodide, diphenylpiperidinomethyldioxolane iodide and the like. ..

Herbal medicines include Akamega wrinkle (Akabu Kashiwa), Asenyaku (Asenyaku), Arnica, Inyoukaku (Innocent sheep), Uiko (Aka), Ukon (Depression), Coptis chinensis (Coptis chinensis), Coptis chinensis (Coptis chinensis) , Ohi (cherry bark), Coptis chinensis (Coptis chinensis), Onji (distant soul), Gajutsu (herbal medicine), Kanokosou (kagokusa), chamomile, caronin (karoujin), kikyo (kikyo), kyonin (anjin), kukoshi (Coptis chinensis), Coptis chinensis (Coptis chinensis), Coptis chinensis (Coptis chinensis), Keihi (Chenpi), Ketsumeishi (Chenpi), Gentiana, Gennoshoko (current evidence), Kouka (Red flower), Coptis chinensis (Coptis chinensis), Goou (Coptis chinensis), Gomishi (Gomiko), Saishin (Spicy), Sanshishi (Yamabiko), Zion (Shien), Jikoppi (Chenpi), Shikon (Purple root), Shakuyaku (Crude drug), Jakou (Ginger), Shajin (Sasan), Shazenshi (Car front child), Shazensou (Car front grass), Beast gall (including Yutan (bear gall)), Ginger (Ginger), Jiryu (Coptis dragon), Shini (Spicy), Sexan (Stone 蒜), Senega, Senkyu ( Kawakyu), Zenko (Maekhu), Senburi (Senburi), Sojutsu (Soujou), Souhakuhi (Kuwashirohide), Soyo (Suha), Taisan (Coptis chinensis), Tincture carrot (Takebushi carrot), Chinpi (Chenpi) , Touki (Toki), Tokon (Vomiting root), Nantenjitsu (Nantenmi), Carrot (Ginseng), Baimo (Shell mother), Bakumondou (Mugimon winter), Hange (Half-summer), Bankouca (Bankohana), Hampi (Anti-nose), Byakushi (white), Byakujutsu (white 朮), Bukuryo (Coptis chinensis), Buttonpi (peony skin), Yobaihi (yang plum skin), Rokujo (deer mushroom) and other crude drugs and their extracts (extracts, tinctures, Dried extract, etc.) and the like.

Chinese prescriptions include Keishito (Keishito), Kososan (Kososan), Psychokeisito (Saiko Keishito), Shosaikoto (Shosaikoto), Bakumondoto (Mai Men Dong Tang), Hangekobokuto. (Hangekobokuto) and the like.

The pharmaceutical composition of the present invention can be appropriately used for the treatment / alleviation of corresponding diseases / symptoms according to the known efficacy of various crude drugs and the like. Among them, since the pharmaceutical composition of the present invention contains loxoprofen, which is a kind of NSAID, or a salt thereof, it can be used as a medical drug or an OTC drug. Specifically, for example, osteoarthritis, muscle pain and It has the efficacy or effect of anti-inflammatory / analgesic of diseases and symptoms selected from swelling / pain after trauma, and is useful as an analgesic / anti-inflammatory agent.

Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited to these examples.
[Test Example 1] Examination of storage stability of pharmaceutical composition containing Phellodendron amurensis or its extract Appearance of the following samples 1-A and 1-B prepared immediately before the start of storage and after storage at 80 ° C. for 1 week. (Presence or absence of precipitation) was visually evaluated.
The results are shown in Table 1.

<Sample 1-A>
0.7 g of Phellodendron amur soft extract (manufactured by Nippon Powder Yakuhin Co., Ltd .: trade name: Phellodendron amur soft extract) (2.31 g in terms of crude drug) was dissolved and suspended in purified water to obtain 100 g of Sample 1-A in total.
<Sample 1-B>
Phellodendron amur soft extract (manufactured by Nippon Powder Yakuhin Co., Ltd .: trade name Oubaku soft extract) 0.7 g (crude drug equivalent amount 2.31 g) and loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd .: trade name Nippon Pharmacopoeia Loxoprofen) 1.13 g of sodium hydrate) was dissolved and suspended in purified water to obtain 100 g of sample 1-B in total.

As is clear from the test results shown in Table 1, in the sample solution (Sample 1-A) containing only the Phellodendron amur extract alone, precipitation was observed immediately before the start of storage, but in addition to the Phellodendron amur extract. In the sample solution (Sample 1-B) containing loxoprofen sodium hydrate, only a slight amount of precipitation was observed even after storage at 80 ° C. for 1 week.
From such test results, it was clarified that loxoprofen or a salt thereof has an action of suppressing precipitation formation of a hydrous composition containing Phellodendron amurensis or an extract thereof and improving storage stability. It is presumed that this is because loxoprofen or a salt thereof solubilizes Phellodendron amurensis or an extract thereof in the hydrous composition.

From the above test results, it was clarified that the pharmaceutical composition containing loxoprofen or a salt thereof together with Phellodendron amurensis or an extract thereof exhibits excellent storage stability.

[Test Example 2] Examination of storage stability of pharmaceutical composition containing licorice or its extract Appearance of the following samples 2-A and 2-B immediately before the start of storage and after storage at 80 ° C. for 2 days. (Presence or absence of precipitation) was visually evaluated.
The results are shown in Table 2.

<Sample 2-A>
1 g (4 g of crude drug equivalent) of licorice extract (manufactured by Nippon Powder Chemicals Co., Ltd .: trade name (bureau) licorice extract) was dissolved and suspended in purified water to obtain 100 g of sample 2-A.
<Sample 2-B>
Licorice extract (manufactured by Nippon Powder Yakuhin Co., Ltd .: trade name (bureau) licorice extract) 1 g (crude drug equivalent 4 g) and loxoprofen sodium hydrate (manufactured by Daiwa Yakuhin Kogyo Co., Ltd .: trade name Nippon Pharmacopoeia Loxoprofen sodium hydrate) ) 1.13 g was dissolved and suspended in purified water to obtain a total volume of 100 g of Sample 2-B.

As is clear from the test results shown in Table 2, in the sample solution (Sample 2-A) containing licorice alone, precipitation was observed after storage at 80 ° C. for 2 days, but loxoprofen was observed in addition to licorice. In the sample solution containing sodium hydrate (Sample 2-B), no precipitation was observed even after storage at 80 ° C. for 2 days.
From such test results, it was clarified that loxoprofen or a salt thereof has an action of suppressing precipitation formation of a hydrous composition containing licorice or an extract thereof and improving storage stability. It is presumed that this is because loxoprofen or a salt thereof solubilizes licorice or its extract in the hydrous composition.

From the above test results, it was clarified that the pharmaceutical composition containing loxoprofen or a salt thereof together with licorice or an extract thereof exhibits excellent storage stability.

[Test Example 3] Examination of storage stability of pharmaceutical composition containing glycyrrhetinic acid or a salt thereof The appearance of the following samples 3-A and 3-B immediately before the start of storage and after storage at 80 ° C. for 1 day. (Presence or absence of separation) was visually evaluated.
The results are shown in Table 3.

<Sample 3-A>
1 g of glycyrrhetinic acid (manufactured by Alps Pharmaceutical Co., Ltd .: trade name: glycyrrhetinic acid) was dissolved and suspended in a 10% ethanol aqueous solution to obtain a total volume of 100 g of sample 3-A.
<Sample 3-B>
1 g of glycyrrhetinic acid (manufactured by Alps Pharmaceutical Co., Ltd .: trade name glycyrrhetinic acid) and 1.13 g of loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name Nippon Pharmacopoeia Loxoprofen sodium hydrate) in a 10% ethanol aqueous solution It was dissolved and suspended to obtain a total volume of 100 g of Sample 3-B.

As is clear from the test results shown in Table 3, in the sample solution (Sample 3-A) containing only glycyrrhetinic acid alone, separation of powdery substance was observed immediately before the start of storage, but in addition to glycyrrhetinic acid. In the sample solution (Sample 3-B) containing loxoprofen sodium hydrate, no separation was observed even after storage at 80 ° C. for 1 day.
From such test results, loxoprofen or a salt thereof suppresses the separation of a hydrous composition containing glycyrrhetinic acid which is a hydrolyzate of an extract of licorice (glycyrrhizinic acid) or a salt thereof, and has an action of improving storage stability. It became clear to have. It is presumed that this is because loxoprofen or a salt thereof solubilizes glycyrrhetinic acid, which is a hydrolyzate of licorice extract, or a salt thereof in a hydrous composition.

From the above test results, it was clarified that the pharmaceutical composition containing loxoprofen or a salt thereof together with glycyrrhetinic acid or a salt thereof exhibits excellent storage stability.

[Test Example 4] Examination of storage stability of pharmaceutical composition containing Japanese pepper or its extract The following samples 4-A and 4-B were prepared and stored immediately before the start of storage and after storage at 80 ° C. for 1 week. The appearance (presence or absence of precipitation) was visually evaluated.
The results are shown in Table 4.

<Sample 4-A>
0.3 g of Japanese pepper soft extract (manufactured by Alps Pharmaceutical Industry Co., Ltd .: trade name: Japanese pepper soft extract) (1 g in terms of crude drug) was dissolved and suspended in purified water to obtain 100 g of sample 4-A.
<Sample 4-B>
Sansho Soft Extract (manufactured by Alps Pharmaceutical Industry Co., Ltd .: trade name Sansho Soft Extract) 0.3 g (crude drug equivalent 1 g) and loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name Nippon Pharmacopoeia Loxoprofen sodium) 1.13 g of hydrate) was dissolved and suspended in purified water to obtain 100 g of sample 4-B in total.

As is clear from the test results shown in Table 4, in the sample solution (Sample 4-A) containing only the Japanese pepper soft extract alone, precipitation was observed immediately before the start of storage, but the Japanese pepper soft extract contained In addition, in the sample solution (Sample 4-B) containing loxoprofen sodium hydrate, no precipitation was observed even after storage at 80 ° C. for 1 week.
From such test results, it was clarified that loxoprofen or a salt thereof has an action of suppressing precipitation formation of a hydrous composition containing sansho or an extract thereof and improving storage stability. It is presumed that this is because loxoprofen or a salt thereof solubilizes Japanese pepper or an extract thereof in the hydrous composition.

From the above test results, it was clarified that the pharmaceutical composition containing loxoprofen or a salt thereof together with Japanese pepper or an extract thereof exhibits excellent storage stability.

[Test Example 5] Examination of storage stability of pharmaceutical composition containing horse chestnut seeds or an extract thereof The following samples 5-A and 5-B were prepared and stored immediately before the start of storage and after storage at 80 ° C. for 1 day. The appearance (presence or absence of coloring) of horse chestnut was visually evaluated.
The results are shown in Table 5.

<Sample 5-A>
0.5 g (5 g of crude drug equivalent) of horse chestnut seed extract (manufactured by Ichimaru Falcos Co., Ltd .: trade name Falcorex Maronie B) was dissolved and suspended in purified water to obtain 100 g of sample 5-A.
<Sample 5-B>
Horse chestnut seed extract (manufactured by Ichimaru Falcos Co., Ltd .: trade name Falcorex Maronie B) 0.5 g (crude drug equivalent 5 g) and loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name Japan Pharmacopoeia Loxoprofen sodium water) 1.13 g of Japanese horse chestnut) was dissolved and suspended in purified water to obtain 100 g of sample 5-B in total.

As is clear from the test results shown in Table 5, in the sample solution (Sample 5-A) containing only the horse chestnut seed extract alone, yellow coloring was observed immediately before the start of storage, but the horse chestnut seed extract contained the horse chestnut seed extract. In addition, the coloration was slight in the sample solution (Sample 5-B) containing horse chestnut hydrate.
From such test results, it was clarified that loxoprofen or a salt thereof has an action of suppressing coloring of a water-containing composition containing horse chestnut seeds or an extract thereof and improving storage stability. It is presumed that this is because loxoprofen or a salt thereof solubilizes horse chestnut seeds or an extract thereof in the hydrous composition.

From the above test results, it was clarified that a pharmaceutical composition containing loxoprofen or a salt thereof together with horse chestnut seeds or an extract thereof exhibits excellent storage stability.

[Test Example 6] Examination of storage stability of pharmaceutical composition containing pepper or its extract Appearance of the following samples 6-A and 6-B prepared immediately before the start of storage and after storage at 80 ° C. for 1 day. (Presence or absence of insoluble matter formation) was visually evaluated.
The results are shown in Table 6.

<Sample 6-A>
0.5 g of pepper extract (manufactured by Nippon Powder Chemicals Co., Ltd .: trade name: pepper extract B) (6.25 g in terms of crude drug) was dissolved and suspended in purified water to obtain 100 g of sample 6-A.
<Sample 6-B>
Togarashi extract (manufactured by Nippon Powder Chemicals Co., Ltd .: trade name: Togarashi extract B) 0.5 g (crude drug equivalent amount 6.25 g) and loxoprofen sodium hydrate (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium water) 20 g of Japanese product) was dissolved and suspended in purified water to obtain 100 g of Sample 6-B in total.

As is clear from the test results shown in Table 6, in the sample solution (Sample 6-A) containing only the pepper extract alone, a small amount of insoluble matter was observed immediately before the start of storage, and after storage at 80 ° C. for 1 day. However, in the sample solution (Sample 6-B) containing loxoprofen sodium hydrate in addition to the pepper extract, no precipitation was observed even after storage at 80 ° C. for 1 day. ..
From such test results, it was clarified that loxoprofen or a salt thereof has an action of suppressing the precipitation formation of a hydrous composition containing pepper or an extract thereof and improving the storage stability. It is presumed that this is because loxoprofen or a salt thereof solubilizes the pepper or its extract in the hydrous composition.

From the above test results, it was clarified that the pharmaceutical composition containing loxoprofen or a salt thereof together with the pepper or its extract exhibits excellent storage stability.

Production Example 1 (Gel agent)
A gel agent containing the following components in 100 g was produced by a conventional method.
Loxoprofen sodium hydrate 1.13g
Glycyrrhetinic acid 0.2g
Nonanoic acid vanillylamide 0.025 g
l-menthol 3g
Chlorpheniramine maleate 0.1g
Hydroxypropyl Methyl Cellulose 1g
Carboxyvinyl polymer 1.2g
1,3-butylene glycol 5g
Triethanolamine 1.5g
Ethanol 20g
Total amount of purified water 100g

Production Example 2 (tape)
A tape agent (plaster agent) containing the following components in 100 g was produced by a conventional method.
Loxoprofen sodium hydrate 1.13g
Pepper extract 0.4g (Crude drug equivalent: 4g)
l-menthol 6g
Chlorpheniramine maleate 0.1g
SIS copolymer 30g
Polyisobutylene 20g
Hydrogenated rosin glycerin ester 25g
Dibutylhydroxytoluene 0.5g
Crotamiton 2g
Liquid paraffin 100g

Production Example 3 (Gel agent)
A gel agent (gel cream agent) containing the following components in 100 g was produced by a conventional method.
Loxoprofen sodium hydrate 1.13g
Licorice extract 0.4g (Crude drug equivalent: 4g)
l-menthol 2g
Polyvinyl alcohol 0.2g
Salicylic acid glycol ester 2g
Carboxyvinyl polymer 1g
Glycerin 10g
Octyldodecanol 10g
Glycerin monostearate 0.5 g
Polyoxyl stearate 0.5g
Isopropyl myristate 5g
Lauro Macrogol 1.5g
Triethanolamine 1g
Total amount of purified water 100g

Production Example 4 (Pap agent)
By a conventional method, a poultice containing the following components in 100 g was produced.
Loxoprofen sodium hydrate 1.13g
Phellodendron powder 1g (Crude drug equivalent: 5g)
Sansho 1g
Horse chestnut seeds 3g
l-menthol 3g
Polyvinyl alcohol 0.8g
Polyacrylic acid partially neutralized product 7g
Carmelose sodium 5g
N-methyl-2-pyrrolidone 2g
Concentrated glycerin 25g
Polysorbate 80 0.3g
Aluminum hydroxide gel 0.05g
Titanium oxide 1g
Talc 2g
Tartaric acid 0.6g
Sodium edetate hydrate 0.1g
Kaolin 2.5g
Sodium bisulfite 0.3g
Total amount of purified water 100g

Production Example 5 (lotion agent)
A lotion containing the following components in 100 g was produced by a conventional method.
Loxoprofen sodium hydrate 1.13g
Glycyrrhetinic acid 0.1g
Pelargonic acid vanillylamide 0.1g
Peppermint oil 6g
Chlorpheniramine maleate 0.5g
Diisopropyl adipate 5 g
Isopropanol 40g
Hydroxypropyl Methyl Cellulose 0.1g
Polyethylene glycol 1g
Sodium bisulfite 0.2g
Total amount of purified water 100g

Production Example 6 (tape)
A tape agent (plaster agent) containing the following components in 100 g was produced by a conventional method.
Loxoprofen sodium hydrate 1.13g
Pelargonic acid vanillylamide 0.12g
l-menthol 1g
Chlorpheniramine maleate 0.5g
SIS copolymer 30g
Polyisobutylene 20g
Hydrogenated rosin glycerin ester 25g
Dibutylhydroxytoluene 0.5g
Crotamiton 2g
Liquid paraffin 100g

Production Example 7 (cream)
A cream containing the following components in 100 g was produced by a conventional method.
Loxoprofen sodium hydrate 1.13g
Horse chestnut seed extract 0.3g (Crude drug equivalent: 3g)
Pelargonic acid vanillylamide 0.12g
dl-camphor 4g
Polyvinyl alcohol 0.2g
Carboxyvinyl polymer 0.8g
Sodium edetate hydrate 1g
Sodium bisulfite 0.1 g
Octyldodecyl myristic acid 10g
Diisopropyl adipate 5 g
Glycerin monostearate 2g
Sorbitan monostearate 0.5g
Polyoxyethylene sorbitan monostearate 1 g
Paraben 0.2g
Sodium hydroxide 0.1g
Total amount of purified water 100g

Production Example 8 (Pap agent)
By a conventional method, a poultice containing the following components in 100 g was produced.
Loxoprofen sodium hydrate 1.13g
Horse chestnut seed extract 0.3g (Crude drug equivalent: 3g)
Pelargonic acid vanillylamide 0.1g
l-menthol 3g
Polyvinyl alcohol 1g
Polyacrylic acid partially neutralized product 7g
Methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsion
5g
Carmelose sodium 5g
Crotamiton 2g
Concentrated glycerin 25g
Polysorbate 80 0.3g
Aluminum hydroxide gel 0.05g
Titanium oxide 1g
Talc 2g
Tartaric acid 0.6g
Sodium edetate hydrate 0.1g
Kaolin 2.5g
Sodium bisulfite 0.3g
Total amount of purified water 100g

Production Example 9 (Pap agent)
By a conventional method, a poultice containing the following components in 100 g was produced.
Loxoprofen sodium hydrate 1.13g
Japanese pepper powder 1g
l-menthol 3g
Polyvinyl alcohol 0.8g
Polyacrylic acid partially neutralized product 7g
Carmelose sodium 5g
N-methyl-2-pyrrolidone 2g
Concentrated glycerin 25g
Polysorbate 80 0.3g
Aluminum hydroxide gel 0.05g
Titanium oxide 1g
Talc 2g
Tartaric acid 0.6g
Sodium edetate hydrate 0.1g
Kaolin 2.5g
Sodium bisulfite 0.3g
Total amount of purified water 100g

According to the present invention, it is possible to provide a pharmaceutical composition containing crude drugs and the like and having excellent storage stability (particularly, storage stability under high temperature conditions), and can be used in the pharmaceutical industry and the like.

Claims (6)

A pharmaceutical composition containing vanillylamide nonanoic acid and loxoprofen or a salt thereof, which is a water-containing composition. Loxoprofen or a salt thereof is contained in an amount of 0.5 to 20% by mass in terms of loxoprofen sodium anhydride with respect to the total mass of the pharmaceutical composition, and nonanoic acid vanillylamide is 0.001 to 0 with respect to the total mass of the pharmaceutical composition. The pharmaceutical composition according to claim 1, which contains 5.5% by mass. The pharmaceutical composition according to claim 1 or 2, wherein loxoprofen or a salt thereof contains 0.001 to 0.02 parts by mass of nonanoic acid vanillylamide with respect to 1 part by mass in terms of sodium loxoprofen anhydride. The pharmaceutical composition according to any one of claims 1 to 3 , which is administered parenterally. The pharmaceutical composition according to any one of claims 1 to 4 , which is semi-solid or liquid. The pharmaceutical composition according to any one of claims 1 to 5 , which is a liniment agent, lotion agent, external aerosol agent, pump spray agent, ointment agent, cream agent, gel agent, tape agent or poultice agent.