JP2012046445A - Loxoprofen-containing pharmaceutical preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a stable solid preparation containing loxoprofen or a salt thereof, and a glycyrrhizic acid derivative or a salt thereof.SOLUTION: The pharmaceutical preparation includes the loxoprofen or the salt thereof, the glycyrrhizic acid derivative or the salt thereof, and a drier in a container.

Description

  The present invention relates to a pharmaceutical preparation comprising loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof.

  Loxoprofen is a type of non-steroidal anti-inflammatory analgesic (NSAID), including rheumatoid arthritis, osteoarthritis, low back pain, shoulder periarthritis, cervical-shoulder arm syndrome, toothache, acute upper respiratory inflammation, post-surgical / post-traumatic It is known as effective for anti-inflammatory, analgesic and antipyretic after tooth extraction (Non-patent Document 1).

Loxoprofen has been studied for combining with various drugs because of its excellent pharmacological action. Examples of the action obtained by the combination include enhancement of anti-inflammatory, analgesic and antipyretic effects by combining with caffeine, ethenamide and acetaminophen (Patent Document 1), carbinoxamine maleate, chlorpheniramine malee Of nasal congestion by combining with acid salt, ketotifen fumarate, mequitazine and epinastine hydrochloride (Patent Document 2), inhibitory effect on goblet cell hyperplasia by combining with azelastine hydrochloride and mequitazine (Patent Document 3), etc. Is mentioned.
Further, combining loxoprofen with bromhexine hydrochloride or ambroxol hydrochloride enhances the effect on cough symptoms (Patent Document 4) and suppresses goblet cell hyperplasia (Patent Document 5), and combines loxoprofen with bromhexine hydrochloride. There are known anti-inflammatory, analgesic and antipyretic effects (Patent Document 6).

  It is also known that loxoprofen enhances the antihistamine action of chlorpheniramine maleate and clemastine fumarate (Patent Document 6). In this patent document, combinations of loxoprofen with various drugs are studied. In addition, formulation examples in which loxoprofen and various drugs are combined are described. Furthermore, a preventive / reducing action of loxoprofen-induced gastric mucosal damage (Patent Document 7) is known by combining with a herbal medicine having a protective action on the stomach / gastric mucosa.

  On the other hand, glycyrrhizic acid and glycyrrhetinic acid have anti-inflammatory action, antiallergic action, gastric mucosal proliferating action, ulcer repairing action and the like, and are used as antiallergic agents and gastrointestinal drugs. These are also known as the main components of licorice (Non-Patent Documents 2, 3 and others).

  An internal solution containing dipotassium glycyrrhizinate and loxoprofen is known (Patent Document 8). Also known are tablets and granules containing licorice containing glycyrrhizic acid and loxoprofen (Patent Document 7). However, it is not known whether loxoprofen interacts with glycyrrhizic acid derivatives. Of course, no solution is known about the solution.

Japanese Patent Laid-Open No. 11-139971 JP 2001-199882 A JP 2008-169193 A JP 2001-172175 A JP 2008-13542 A JP 2000-143505 A JP 2004-161667 A JP 2001-10777 A

15th Amendment Japanese Pharmacopoeia Manual C-4790-4495 Sasakawa Shoten Co., Ltd. OTC Handbook 2008-09 Pages 370-371 Academic Information Distribution Center Co., Ltd. OTC Handbook 2008-09 Page 567 Academic Information Distribution Center Co., Ltd.

First, in order to develop a solid preparation containing loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof, the present inventors examined their storage stability. As a result, the loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof were examined. Surprisingly, it has been found that when the salt is mixed and stored, an interaction occurs between these compounds, and this interaction causes discoloration, solidification, and the like, resulting in a problem in stability.
Accordingly, an object of the present invention is to provide a stable solid preparation containing loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof.

  Therefore, the present inventors further studied to solve this problem, and suppressed the interaction by storing loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof in the presence of a desiccant. I found out that I can.

That is, the present invention provides a pharmaceutical preparation comprising loxoprofen or a salt thereof, a glycyrrhizic acid derivative or a salt thereof, and a desiccant in a container.
The present invention also provides a pharmaceutical preparation comprising a solid preparation containing loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof and a desiccant in a container.
In addition, the present invention provides loxoprofen or a salt thereof, a glycyrrhizic acid derivative or a salt thereof, wherein the loxoprofen or a salt thereof, and a glycyrrhizic acid derivative or a salt thereof are stored in the presence of a desiccant, and the interaction is suppressed. The present invention provides a method for producing a solid preparation containing a salt.
The present invention also includes a step of storing a solid preparation containing loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof in the presence of a desiccant, wherein the loxoprofen or a salt thereof and a glycyrrhizic acid derivative or The present invention provides a method for producing a pharmaceutical preparation comprising a solid preparation containing the salt and a desiccant in a container.

According to the present invention, the interaction between loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof can be suppressed. Therefore, it is possible to provide a solid preparation containing loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof having excellent storage stability.
Moreover, the solid formulation with which interaction was suppressed including a loxoprofen or its salt, and a glycyrrhizic acid derivative or its salt can be provided easily and cheaply without passing through a complicated process.

The pharmaceutical preparation of the present invention contains loxoprofen or a salt thereof, a glycyrrhizic acid derivative or a salt thereof and a desiccant.
Loxoprofen or a salt thereof used in the pharmaceutical preparation of the present invention includes not only loxoprofen but also a pharmaceutically acceptable salt of loxoprofen, and further a solvate with water, alcohol or the like. These are known compounds, and can be produced by known methods, or commercially available products can be used. In the present invention, loxoprofen or a salt thereof is preferably loxoprofen sodium hydrate (chemical name: Monosodium 2- [4-[(2-oxocyclopentyl) methyl] phenyl] propanoate dihydrate).

  The content of loxoprofen or a salt thereof in the pharmaceutical preparation of the present invention may be determined by appropriate examination according to the sex, age, symptoms, etc. of the user, but is 10 to 10 per day in terms of loxoprofen sodium anhydride. The amount that can be taken 300 mg is preferred, and the amount that can be taken 30 to 240 mg is more preferred. The amount that can be taken 60 to 180 mg is particularly preferred.

The glycyrrhizic acid derivative used in the pharmaceutical preparation of the present invention includes not only glycyrrhizic acid but also glycyrrhetinic acid which is a metabolite of glycyrrhizic acid. The glycyrrhizic acid derivative or salt thereof used in the present invention includes glycyrrhizic acid and glycyrrhetinic acid itself as well as pharmaceutically acceptable salts of glycyrrhizic acid and glycyrrhetinic acid.
Examples of the glycyrrhizic acid salt include dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, diammonium glycyrrhizinate, disodium glycyrrhizinate, and trisodium glycyrrhizinate. Examples of the salt of glycyrrhetinic acid include diglycyrrhetinic acid. Potassium etc. are mentioned.

  Moreover, as a glycyrrhizic acid derivative or its salt, a glycyrrhizic acid or its salt, a glycyrrhetic acid or its salt is preferable, and 1 type, or 2 or more types may be used among these. Among them, glycyrrhizic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, glycyrrhetinic acid, and dipotassium glycyrrhetinate are preferable, and glycyrrhizic acid, dipotassium glycyrrhizinate, and monoammonium glycyrrhizinate are more preferable. These are known compounds and may be produced by known methods, or commercially available products may be used.

Moreover, as said glycyrrhizic acid derivative or its salt, the licorice (licorice) or licorice extract which contains these as a component can also be used.
The licorice refers to the roots and strons of Glycyrrhiza uralensis F., Glycyrrhiza glabra L. or other related genera as described in the 15th Amendment Japanese Pharmacopoeia. The shape of licorice can be adjusted as needed, and it can be cut or crushed into small pieces and small lumps or pulverized into powder.
As the licorice extract used in the present invention, licorice is dried or dried after being cut or pulverized to an appropriate size (licorice powder), a leaching solution obtained by adding an appropriate leaching agent to this, Further, liquids obtained by concentrating the leachate (crucible licorice extract, licorice extract, licorice tincture), and leaching liquid and liquid obtained by concentrating the leachate (dried licorice extract powder, dried licorice extract) are included. In addition, the said concentration etc. can be performed by the well-known method as described in 15th revision Japanese Pharmacopoeia preparation general rules.

  Examples of the leaching agent include lower monohydric alcohols such as methanol, ethanol and n-butanol; lower polyhydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol and glycerine; ethers such as diethyl ether; acetone, Ketones such as ethyl methyl ketone; esters such as ethyl acetate; halogenoalkanes such as dichloromethane and chloroform; aromatic hydrocarbons such as benzene and toluene; and water. These may be used alone or in combination of two or more. Furthermore, the extract can be dried.

  In the present invention, when licorice is used as the glycyrrhizic acid derivative or a salt thereof, it is preferable to use licorice powder, licorice extract, licorice crude extract, licorice dry extract, or licorice extract powder. In addition, Kampo prescriptions containing licorice can also be used, and the Kampo prescription includes kakkon-yu, katsue-yu, kososan, saiko-ke-to, sho-saiko-to, shosei-ryu, barmon-fu-to, mao-to Etc. As described above, these may be produced by a known method, or commercially available products may be used.

  In the present invention, the content of the glycyrrhizic acid derivative or a salt thereof is not particularly limited, and may be determined by appropriately examining according to the sex, age, symptoms, etc. of the user. For example, as glycyrrhizic acid, an amount that can be taken 0.1 to 400 mg per day is preferable, an amount that can be taken 0.5 to 300 mg is more preferable, and an amount that can be taken 5 to 200 mg is particularly preferable.

  Moreover, a part or all of a glycyrrhizic acid derivative or its salt can be substituted for the above-mentioned licorice. When licorice is used as the glycyrrhizic acid derivative or salt thereof, it may be determined by appropriate examination according to the sex, age, symptoms, etc. of the user, but it is 0.01-20 g per day (concentration of drug substance) Amount) The amount that can be taken is preferred, the amount that can be taken 0.1 to 10 g (raw material equivalent amount) is more preferred, and the amount that can be taken 0.5 to 5 g (raw material equivalent amount) is particularly preferred.

  The content ratio of loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof contained in the pharmaceutical preparation of the present invention may be determined by appropriately examining according to the daily dose of each component described above, What contains 0.0003-40 mass parts of a glycyrrhizic acid derivative or its salt with respect to 1 mass part of loxoprofen or its salt in terms of loxoprofen sodium anhydride is preferable, and what contains 0.002-10 mass parts More preferably, 0.02 to 4 parts by mass is particularly preferable. On the other hand, when licorice is used as the glycyrrhizic acid derivative or a salt thereof, it is preferable that licorice is contained in an amount of 0.02 to 10 parts by mass in terms of a crude drug to 1 part by mass in terms of loxoprofen sodium anhydride.

Loxoprofen or a salt thereof, and a glycyrrhizic acid derivative or a salt thereof included in the pharmaceutical preparation of the present invention include loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof in terms of convenience of administration and management of a drug dose. A solid preparation is preferred.
The solid preparation of the present invention can be produced and formulated based on a known method described in the 15th revision Japanese Pharmacopoeia General Rules for Preparations. Examples of the dosage form of the solid preparation include tablets, powders, granules, fine granules, pills, capsules and the like.
In the present invention, loxoprofen or a salt thereof is preferably contained in an amount of 0.4 to 50% by mass in terms of anhydrous loxoprofen sodium, more preferably 1.2 to 30% by mass, based on the total mass of the solid preparation. Preferably, the content is 1.2 to 25% by mass.
Moreover, it is preferable to contain 0.004-70 mass% of glycyrrhizic acid derivative or its salt with respect to a solid formulation total mass, It is more preferable to contain 0.02-50 mass%, 0.1-40 The content by mass is particularly preferred.
As the solid preparation, in view of interaction inhibition, it is more preferable that loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof in the solid preparation are contained so as not to contact each other, manufactured and formulated. The preparations prepared so as to be substantially in contact with each other can be easily understood by general pharmaceutical technology researchers, using appropriate formulation additives based on known methods. Can be manufactured and formulated. Specifically, as the form of the solid preparation, the following (a) to (f) can be exemplified, and these can be produced and formulated by a known method.

(I) Powders or granules produced by granulating any one of loxoprofen or a salt thereof, and a glycyrrhizic acid derivative or a salt thereof into a granular material, and containing the other without granulation. Etc., as well as a preparation in which the granular material is further coated by an appropriate method.
(B) Loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof are separately granulated by an appropriate method to form granules, and powders and granules produced by containing them, and further the granules Formulation coated by an appropriate method.
(C) A capsule filled with the powder or granule prepared in (i) or (b) above. (D) Tablets obtained by tableting the granular material produced in (b) or (b) above.
(E) A multi-layer tablet prepared so that loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof do not contact each other, and a preparation in which the multi-layer tablet is further coated by an appropriate method. As the multi-layered tablet, those in which loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof are located in different layers are preferable. As a multi-layered tablet having three or more layers, a layer containing loxoprofen or a salt thereof and a glycyrrhizic acid derivative Or it is more preferable that the layers containing the salt are positioned so as not to contact each other. In addition, as the loxoprofen or a salt thereof and the glycyrrhizic acid derivative or the salt thereof, the granular material produced in the above (i) or (b) can be used.
(F) A dry-coated tablet in which any one of loxoprofen or a salt thereof, and a glycyrrhizic acid derivative or a salt thereof is arranged in a nuclear tablet, and a preparation in which the dry-coated tablet is further coated by an appropriate method. In addition, as the loxoprofen or a salt thereof and the glycyrrhizic acid derivative or the salt thereof, the granular material produced in the above (i) or (b) can be used.

  Examples of the route of administration of the solid preparation of the present invention include oral and parenteral such as rectal and vaginal, and the solid preparation of the present invention is preferably an oral administration preparation. In addition, when administered orally, the solid preparation according to the present invention can be divided into about 1 to 4 times per day and taken before meals, between meals, after meals, and before going to bed.

  In the present invention, the desiccant is not particularly limited as long as it can suppress or improve the interaction when stored together with loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof. Also, the shape is not limited, and examples thereof include a plate-shaped or bag-shaped sheet mold, a cylinder (tablet mold), etc., and a cylinder with paper wrapping or film coating. But you can.

  Examples of the desiccant include silica gel, silica alumina gel (allophane), natural zeolite, synthetic zeolite (molecular sieve), calcium chloride, quicklime (calcium oxide), bentonite clay (montmorillonite), magnesium chloride and magnesium oxide. 1 type or 2 types or more are mentioned. In addition, you may mix these and activated carbon. Among these, one or more selected from silica gel, silica alumina gel (allophane), synthetic zeolite (molecular sieve) and calcium chloride are more preferable, and synthetic zeolite is particularly preferable in terms of interaction suppression.

  Various desiccants are commercially available. For example, Shiblet, MS-Tablet, MS-Serum W, Tokai Gel, Decite Kite 25, Alp sheet, Toray Chemical Co., Ltd. ) Packaged items, Dryan (registered trademark) tablets, Dryan (registered trademark) sheets, Sekawa, Allosheet, Zeosheet, Shinzo Kasei Co., Ltd., OZO Co., Ltd. OZO, IDi Co., Ltd. IDi-packing desiccant and the like.

The content of the desiccant may be determined by appropriate examination, but is preferably 0.01 to 35 parts by mass, more preferably 0.15 to 17 parts by mass with respect to 1 part by mass of loxoprofen or a salt thereof.
In addition, for 1 part by mass of a solid preparation containing loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof, 0.001 to 1.5 parts by mass is preferable, and 0.004 to 1 part by mass is more preferable. 0.004-0.4 mass part is further more preferable.

  In the pharmaceutical preparation of the present invention, a drug other than loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof, for example, an antipyretic analgesic agent, an antihistamine, an antitussive, a noscapine, a bronchodilator, an expectorant, a hypnotic sedative In addition, one or more selected from the group consisting of vitamins, anti-inflammatory agents, gastric mucosa protective agents, anticholinergic agents, herbal medicines, caffeine, xanthine components and the like may be included. These components are preferably contained in the solid preparation.

  Examples of antipyretic analgesics include aspirin, aspirin aluminum, acetaminophen, isopropylantipyrine, ibuprofen, ethenzamide, sazapyrine, salicylamide, sodium salicylate, thiaramide hydrochloride, lactylphenetidine, and the like.

  Antihistamines include, for example, azelastine hydrochloride, alimemazine tartrate, istipendil hydrochloride, iproheptin hydrochloride, epinastine hydrochloride, emedastine fumarate, carbinoxamine diphenyl disulfonate, carbinoxamine maleate, clemastine fumarate. Acid salt, dl-chlorpheniramine maleate, d-chlorpheniramine maleate, ketotifen fumarate, dipheterol hydrochloride, dipheterol phosphate, diphenylpyraline hydrochloride, diphenylpyraline theocrate, diphenhydramine Hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, triprolidine hydrochloride, tripelenamine hydrochloride, tondilamine hydrochloride, phenetazine hydrochloride, promethazine hydrochloride, promethad Methylene two salicylates, mequitazine, methdilazine hydrochloride, main blanking hydro Linna Paji sill acid salts.

  Antitussives include, for example, aloclamide hydrochloride, eprazinone hydrochloride, carbetapentane enoate, cloperastine hydrochloride, cloperastine phendizoate, codeine phosphate, dihydrocodeine phosphate, dibutarate sodium, dimemorphan Examples thereof include phosphate, dextromethorphan hydrobromide, dextromethorphan / phenol phthaline salt, tipepidine citrate, and tipepidine hibenzate.

Examples of noscapine include noscapine hydrochloride and noscapine.
Examples of bronchodilators include trimethquinol hydrochloride, phenylpropanolamine hydrochloride, phenylephrine hydrochloride, pseudoephedrine hydrochloride, pseudoephedrine sulfate, methylephedrine, dl-methylephedrine hydrochloride, l-methylephedrine hydrochloride, dl. -Methylephedrine saccharin salt, methoxyphenamine hydrochloride, etc. are mentioned.

  As an expectorant, for example, ambroxol hydrochloride, ammonia fennel, ethylcysteine hydrochloride, ammonium chloride, carbocysteine, guaifenesin, potassium guaiacolsulfonate, potassium cresolsulfonate, bromhexine hydrochloride, methylcysteine hydrochloride, Examples thereof include l-menthol and lysozyme hydrochloride.

Examples of the hypnotic sedative include allyl isopropyl acetyl urea and bromovalerylurea.
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 nitrate, dicetiamine hydrochloride, sethiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, octothiamine, chicotiamine, thiamine disulfide, bisibutamine, bisbenchamine, prosultiamine, benfotiamine, riboflavin, riboflavinline Acid ester, riboflavin butyrate, sodium riboflavin phosphate, panthenol, pantethine, calcium pantothenate, sodium pantothenate, pyridoxine hydrochloride, pyridoxal phosphate, cyanocobalamin, mecoba Lamin, ascorbic acid, sodium ascorbate, calcium ascorbate, hesperidin, etc.).

  Examples of the anti-inflammatory agent include seaprose, semi-alkaline proteinase, serrapeptase, tranexamic acid, proctase, pronase, bromelain and the like.

  Examples of the gastric mucosa protective agent include aminoacetic acid, aldioxa, magnesium silicate, gefarnate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate (aluminum glycinate), aluminum hydroxide gel, Aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / sodium bicarbonate coprecipitation product, aluminum hydroxide / calcium carbonate / magnesium carbonate coprecipitation product, magnesium hydroxide / potassium aluminum sulfate coprecipitation product , Sucralfate, cetraxate hydrochloride, sofalcone, magnesium carbonate, teprenone, copper chlorophyllin potassium, copper chlorophyllin sodium, magnesium metasilicate aluminate, methylmethionine sulfate Niumukurorido, and the like.

  Anticholinergic agents include, for example, oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, scopolamine hydrobromide, datsura extract, tipidium bromide, methyl atropine bromide, methyl anisotropin bromide, methyl scopolamine bromide, methyl- 1-hyostiamine bromide, methylbenactidium bromide, pirenzepine hydrochloride, butyl scopolamine bromide, belladonna alkaloid, belladonna extract, belladonna total alkaloid, iodopropamide iodide, diphenylpiperidinomethyldioxolane, funnel extract, funnel root, funnel Examples include root total alkaloid citrate.

  Herbal medicines include, for example, akamegashiwa (red buds), asenyaku (asenyaku), inyoukaku (horny lamb), fennel (yuka), turmeric (depressed gold), engosaku (yenkogyo), enmaiso (extended herb), ogon (yellow jade) ), Ousei (yellow spirit), Owaku (yellow twilight), Spruce (cherry bark), Auren (yellow ream), Onji (distant), Gajutsu (weather), valerian (deer grass), chamomile, caronin (karojin), Kyoukyo (Kikkyo), Kyonin (Kyojin), Kukoshi (Kashiwa), Kukoyo (Kashiwaha), Keigai (Kashiwagi), Keihi (Keiko), Ketsumeishi (Keiko), Gentiana, Gennoshouko (current evidence), Koubushi (Katsukiko) , Goo (gyuhuang), trash (goji), saishin (spicy), sansho (yamabuchi), zion (purple candy), dicoppi (earth bone skin), peonies (glaze), musk Yajin (Shasan), Shazenshi (car front child), Shazenso (car front grass), Beast gall (including Yutan (bear gall)), Syougyo (ginger), Giryu (land dragon), Xinyi (hot potato), Sexan (stone)蒜), Senega, Senkyu (river cucumber), Zenko (mae-hu), Senburi (Senhwa), Sojutsu (蒼朮), Sohakuhi (mulberry white skin), Soyo (Soba), Taisan (Daegu) Chikusetsunjinjin (Bamboo ginseng) ), Clove (chome), Chinpi (Chinese skin), Touki (Tochigi), Tokon (Nanten), Nantenjitsu (Minami Tenmi), Carrot (Ginseng), Baimo (Shell), Bakumondou (Bakumon winter), Pepper ( Lightweight), Hange (half-summer), Bankou (Banka), Hampi (anti-nasal), Byakushi (white), Byakujutsu (white birch), Bukuryu (茯苓), Buttonpi (peony skin), Borei (oyster), Maou ( Herbal medicines such as Mao) and Lokujo Extract (extract, tincture, dry extract, etc.) and the like.

Examples of caffeine include sodium benzoate caffeine, caffeine hydrate, anhydrous caffeine, and citric acid caffeine.
Examples of the xanthine component include aminophylline, diprofylline, theophylline, proxyphylline and the like.

  The container used for the pharmaceutical preparation of the present invention is not particularly limited as long as it can be used as a container for foods, supplements, pharmaceuticals, health foods, and the like, but any of a fixed container and an amorphous container can be used and sealed. What is possible is preferred. Examples of the fixed container include bottles, cans, and boxes. Examples of the amorphous container include bags (pillow packaging, stick packaging, PTP packaging, SP packaging, etc.) and the like. Of these containers, specifically, bottles and bags are preferable.

The forming member of the container is not particularly limited, and examples thereof include paper, glass, a resin or a resin film, or a member such as a metal or a metal film, and a composite structure or a multilayer structure in which these members are appropriately combined. It may be a thing. Moreover, it is preferable that moisture permeation prevention processing is performed about the member which has moisture permeability, such as paper.
The container may be transparent, translucent, or opaque.

  The method of storing loxoprofen or a salt thereof, a glycyrrhizic acid derivative or a salt thereof, and a desiccant used in the present invention in the container is not particularly limited, and any suitable means such as charging them into the container. This can be achieved by arranging according to

  For example, when the container is a bottle, a desiccant (preferably a cylindrical shape (tablet shape)) is placed in the bottle or stored in the back side (inner cap) of the bottle lid, and loxoprofen or The salt and the glycyrrhizic acid derivative or the salt thereof can be achieved by storing in a bottle. When storing in a bottle, loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof are preferably solid preparations containing these.

  In the case where the container is a bag, it can be achieved by storing a desiccant (preferably, a plate-type or bag-shaped sheet type), loxoprofen or a salt thereof, and a glycyrrhizic acid derivative or a salt thereof in the bag. When storing in a bag, loxoprofen or a salt thereof, and a glycyrrhizic acid derivative or a salt thereof are preferably solid preparations containing these.

  Furthermore, the solid preparation of the present invention may be once packaged by SP packaging, PTP packaging, a bag or the like, and then the packaged solid preparation and a desiccant may be enclosed in a bag. For example, a form containing loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof in stick packaging, SP packaging or PTP packaging, and a desiccant packaged in pillow packaging or stick packaging. More specifically, a form in which the solid preparation packed in SP or PTP and a plate-like or bag-like sheet-type desiccant are combined in a pillow package is included. Further, the pillow packaging form may be stored in a box or the like.

  The pharmaceutical preparation of the present invention contains loxoprofen or a salt thereof, which is a kind of NSAID, and a glycyrrhizic acid derivative having anti-inflammatory activity, anti-allergic activity, etc., and further preventing or reducing gastric mucosal damage caused by loxoprofen. , Headache, toothache, pain after tooth extraction, sore throat, ear pain, joint pain, neuralgia, low back pain, muscle pain, stiff shoulder pain, bruise pain, fracture pain, sprain pain, menstrual pain (menstrual pain), pain relief It is effective or effective for antipyretic during cold / fever, cold symptoms (sore throat, chills, fever, headache, joint pain, muscle pain), etc., and is useful as a cold medicine, antipyretic analgesic, etc. is there.

EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.
[Test Example 1] Examination of interaction Loxoprofen sodium hydrate 0.5 g (manufactured by Yamato Pharmaceutical Co., Ltd .: trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate) and dipotassium glycyrrhizinate 0.5 g (manufactured by Maruzen Pharmaceutical: trade name: glycyrrhizin) Acid K2) was mixed, put into a glass bottle (3K standard bottle), and stored at 60 ° C.
Separately, in addition to loxoprofen sodium hydrate and dipotassium glycyrrhizinate, 1 g of synthetic zeolite (manufactured by Shin-Etsu Chemical Co., Ltd .: trade name MS-W1506) was added as a desiccant and stored at 60 ° C. in the same manner.
For each, the state of the mixture immediately after the start of storage, 1 day, 3 days, and 1 week later, ie, the presence or absence of interaction, was evaluated, and the results are shown in Table 1.

As is apparent from Table 1, the mixture of loxoprofen sodium hydrate and dipotassium glycyrrhizinate that had been preserved changed its color to a solidified state after 1 day of storage as a result of interaction. did.
On the other hand, when a desiccant is added, the mixture is found to be less affected and discolored even after one week, and the powder state is maintained, compared to the mixture just mixed. did.

[Production Example 1]
Loxoprofen sodium hydrate 1123.7 g (manufactured by Daiwa Pharmaceutical Co., Ltd., trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate), dipotassium glycyrrhizinate 1100 g (manufactured by Maruzen Pharmaceutical: trade name glycyrrhizic acid K2), hydroxypropylcellulose 123.8 g ( Nippon Soda: trade name HPC-M), carmellose calcium 412.5 g (product name: ECG505), crystalline cellulose 1323.7 g (Asahi Kasei Chemicals: trade name Theolas PH-101) (Fukae Kogyo Co., Ltd .: FS-10 type) was added and mixed, and then 206.3 g of purified water was added and kneaded. The granulated product was put into a fluidized bed dryer (Freund Sangyo: FLO-5 type), dried, and then granulated using a granulator (Okada Seiko: ND-10 type). 4083.7 g of this sized product and 41.3 g of magnesium stearate (manufactured by Taihei Kagaku Kogyo: trade name magnesium stearate (vegetable)) were introduced into a mixer (manufactured by Kotobuki: PM50 type) and mixed, and then the diameter 8 Tableting was performed using a tableting machine (manufactured by Hata Iron Works: HT-AP18SS type) equipped with a 0.0 mm punch, and tablets each having a mass of 250 mg were obtained.

[Production Example 2]
Loxoprofen sodium hydrate 1123.7 g (manufactured by Daiwa Pharmaceutical Co., Ltd .: trade name, Japanese Pharmacopoeia Loxoprofen sodium hydrate), licorice (licorice) 1571.4 g (concentration in bulk drug: 11000 g) (manufactured by Nippon Powdered Drugs: trade name licorice) Extract powder), 123.8 g of hydroxypropyl cellulose (Nippon Soda: trade name HPC-M), 412.5 g of carmellose calcium (trade name: ECG505), 852.3 g of crystalline cellulose (trade name: Asahi Kasei Chemicals: trade name) Theolaus PH-101) was put into a high-speed agitation granulator (Fukae Kogyo Co., Ltd .: FS-10 type) and mixed, and then 206.3 g of purified water was added and kneaded. The granulated product was put into a fluidized bed dryer (Freund Sangyo: FLO-5 type), dried, and then granulated using a granulator (Okada Seiko: ND-10 type). 4083.7 g of this sized product and 41.3 g of magnesium stearate (manufactured by Taihei Kagaku Kogyo: trade name magnesium stearate (vegetable)) were introduced into a mixer (manufactured by Kotobuki: PM50 type) and mixed, and then the diameter 8 Tableting was performed using a tableting machine (manufactured by Hata Iron Works: HT-AP18SS type) equipped with a 0.0 mm punch, and tablets each having a mass of 250 mg were obtained.

[Example 1]
Thirty tablets obtained in Production Example 1 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Chemical Co., Ltd .: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

[Example 2]
30 tablets obtained in Production Example 2 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Chemical Co., Ltd .: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.

  According to the present invention, the interaction between loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof can be suppressed. Therefore, it is possible to provide a solid preparation containing loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof having excellent storage stability.

Claims (13)

  A pharmaceutical preparation comprising loxoprofen or a salt thereof, a glycyrrhizic acid derivative or a salt thereof, and a desiccant in a container.   A pharmaceutical preparation comprising a solid preparation containing loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof and a desiccant in a container.   The pharmaceutical preparation according to claim 1 or 2, wherein the container is a bottle.   The pharmaceutical preparation according to claim 2 or 3, comprising a solid preparation containing loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof, and a desiccant packaged in pillow packaging or stick packaging, which is packaged in stick packaging, PTP packaging or SP packaging. .   The desiccant is selected from the group consisting of silica gel, silica alumina gel (allophane), natural zeolite, synthetic zeolite (molecular sieve), calcium chloride, quicklime (calcium oxide), bentonite clay (montmorillonite), magnesium chloride and magnesium oxide 1 It is a seed | species or 2 or more types, The pharmaceutical formulation of any one of Claims 1-4.   The pharmaceutical preparation according to any one of claims 1 to 5, wherein the loxoprofen or a salt thereof is loxoprofen sodium hydrate.   The pharmaceutical preparation according to claim 6, comprising loxoprofen sodium hydrate in an amount of 10 to 300 mg per day in terms of anhydrous loxoprofen sodium.   The pharmaceutical preparation according to any one of claims 1 to 7, wherein the glycyrrhizic acid derivative or a salt thereof is glycyrrhizic acid or a salt thereof and / or glycyrrhetinic acid or a salt thereof.   The pharmaceutical preparation according to claim 8, wherein the glycyrrhizic acid derivative or a salt thereof is dipotassium glycyrrhizinate.   The pharmaceutical preparation according to any one of claims 1 to 9, comprising 0.1 to 400 mg of glycyrrhizic acid derivative or a salt thereof as a daily dose.   Loxoprofen or a salt thereof, and a glycyrrhizic acid derivative or a salt thereof, comprising a step of storing the loxoprofen or a salt thereof, and a glycyrrhizic acid derivative or a salt thereof in the presence of a desiccant, wherein the interaction is suppressed, A method for producing a solid preparation.   The production method according to claim 11, wherein the preservation is preservation in a container.   A solid containing loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof, comprising a step of storing a solid preparation containing loxoprofen or a salt thereof and a glycyrrhizic acid derivative or a salt thereof in the presence of a desiccant. A method for producing a pharmaceutical preparation comprising a preparation and a desiccant in a container.