JP2018188377A - Pharmaceutical composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a pharmaceutical composition having improved solubility of mequitazine.SOLUTION: It is found out that the coexistence of mequitazine and a rhinitis crude drug effectively improves water solubility of mequitazine; the present invention provides a pharmaceutical composition containing mequitazine, and a rhinitis crude drug.SELECTED DRAWING: None

Description

  The present invention relates to a pharmaceutical composition.

  A medicine containing an antihistamine is known for rhinitis, which is inflammation of the nasal mucosa. For example, as a composition for treating rhinitis containing an antihistamine, Patent Document 1 discloses a composition for treating rhinitis characterized by containing a phenothiazine antihistamine, an anti-inflammatory enzyme and an anti-inflammatory drug. Yes. In addition, mequitazine is known as a kind of antihistamine.

  In addition, treatment with herbal medicine has been performed for rhinitis for a long time.

JP 10-158193 A

  However, it is known that mequitazine is difficult to dissolve in water.

  Therefore, an object of the present invention is to provide a pharmaceutical composition having improved solubility of mequitazine.

  As a result of intensive studies, the present inventors have found that the coexistence of mequitazine and a nasal herbal medicine effectively improves the solubility of mequitazine in water, thereby completing the present invention.

That is, the present invention
[1] A pharmaceutical composition containing mequitazine and a nasal herbal medicine;
[2] The pharmaceutical composition according to the above [1], wherein the rhinitis herbal medicine is at least one selected from the group consisting of Shini, licorice, saishin, ginger, mussel, zenko, juniper, and extracts thereof. object;
[3] The pharmaceutical composition according to [1] or [2] above, containing 3 to 7 mg of the mequitazine as a daily dose for an adult;
[4] The pharmaceutical composition according to any one of [1] to [3], wherein the rhinitis herbal medicine is contained in an amount of 1 to 7000 parts by weight in terms of the active ingredient relative to 1 part by weight of the mequitazine;
[5] The pharmaceutical composition according to any one of [1] to [4], further containing at least one selected from the group consisting of stearic acid and salts thereof;
[6] The pharmaceutical composition according to any one of [1] to [5], which is a solid preparation;
[7] The pharmaceutical composition according to any one of [1] to [6], which is at least one selected from the group consisting of acute rhinitis, allergic rhinitis, and sinusitis;
[8] The pharmaceutical composition according to any one of [1] to [7], which is fast-dissolving and / or fast-releasing.
In another embodiment, the present invention provides a method for imparting water-dispersibility and / or solubility-improving action to a pharmaceutical composition, comprising coexisting mequitazine and a nasal herbal medicine in the pharmaceutical composition. Can also be provided.

  The pharmaceutical composition of the present invention improves the solubility of mequitazine in water by coexisting mequitazine and a rhinitis herbal medicine, and is excellent in the rapid solubility and rapid release of the drug.

[Pharmaceutical composition]
The pharmaceutical composition of the present invention contains mequitazine and a nasal herbal medicine.

[Mequitazine]
Mequitazine is an antiallergic agent known as a nasal secretion inhibitor and also has an antihistamine action. Mequitazine can be obtained as a commercial product or can be produced by a known production method.

  Mequitazine is usually free.

  The dose (dose) of mequitazine may vary depending on the type and amount of nasal herbal medicine, the type and amount of other ingredients, the user's condition (weight, age, symptoms, physical condition, etc.), and the dosage form. From the viewpoint of remarkably exhibiting the effects of the invention, usually, when orally administered to an adult having a body weight of about 60 kg, preferably 3 to 7 mg / day, more preferably 3.5 to 6 mg / day, still more preferably 3.5 to 5 mg. / Day, particularly preferably about 4 mg / day.

  Therefore, the pharmaceutical composition of the present invention is preferably 3 to 7 mg, more preferably 3.5 to 6 mg, still more preferably 3.5 to 5 mg, and particularly preferably 4 mg of mequitazine as a daily dose for an adult. contains.

  The content of mequitazine may vary depending on the type and amount of rhinitis herbal medicine, the type and amount of other ingredients, the condition of the user (weight, age, symptoms, physical condition, etc.), and the dosage form. In the case of a solid preparation, it is usually 0.01 to 20% by weight, preferably 0.02 to 15% by weight, more preferably 0.03 to 10% by weight, based on the total amount of the pharmaceutical composition. When the pharmaceutical composition is a liquid preparation, it is usually 0.01 to 70% by weight, preferably 0.02 to 60% by weight, more preferably 0.03 to 50% by weight, based on the total amount of the pharmaceutical composition. It is. When the solid preparation partially includes the liquid preparation, it is usually 0.01 to 15% by weight, preferably 0.02 to 10% by weight, more preferably 0.03 to 0% by weight based on the total amount of the liquid preparation. 5% by weight. In this specification, liquid preparations include soft capsule contents, hard capsule contents, and the like.

[Rhinitis herbal medicine]
In the present specification, the rhinitis-based crude drug refers to a crude drug having a function of improving rhinitis and related symptoms. Related symptoms of rhinitis include nasal discharge (nasal drip, runny nose, nasal discharge), nasal congestion (nasal congestion), sneezing, sore eyes, pruritus, sore throat, head weight (heavy head), nasal congestion, nose Examples include bleeding and atrophy or hardening of the nasal mucosa. The rhinitis-based crude drug is not limited as long as it is a crude drug having such a function.

  In this specification, rhinitis herbal medicine refers to various parts of a specific herbal medicine (whole, flower, head flower, flower bud, bud, flower spike, leaf, branch, branch leaf, rhizome, root bark, root, bark, fruit, peel, bean. Fruit, seed, etc.) as they are, or dried, pulverized, crushed and extracted, or extracted with an extraction solvent.

  The rhinitis herbal medicine is preferably at least one selected from the group consisting of Shinyi, licorice, saishin, gyoza, shellfish, zenko, peony, and extracts thereof from the viewpoint of remarkably exhibiting the effects of the present invention. More preferably, it is at least one selected from the group consisting of: Shinyi, Daylily, Saishin, Tokyo, and these extracts. A rhinitis system crude drug may be used individually by 1 type, and may be used in combination of multiple types suitably.

  Among the rhinitis-based herbal medicines, Shini is not limited, but is obtained from dried magnolia plants such as magnolia, humoklen, shimoklen, kobushi, tamashiba, or other related plants, including magnoflorin. ing.

  Among rhinitis herbs, licorice is not limited, but is obtained from dried roots and rhizomes of leguminous licorice plants such as Ural licorice and Spanish licorice, and includes glycyrrhizic acid and the like.

  Among rhinitis herbal medicines, Saisin is obtained from dried roots and rhizomes of Echinacea family plants such as Keirinsaicin and Usbasaicin, but includes asarinin and the like.

  Among rhinitis-based crude drugs, ginger is not limited, but can be obtained from raw or dried ginger family ginger rhizome, and includes kingerol and the like.

  Among rhinitis herbal medicines, but not limited to, mussel is obtained from a dried whole plant or flower ear of Lamiaceae.

  Among rhinitis herbal medicines, Zenko can be obtained from, but not limited to, dried Nodake of the family Apiaceae or dried roots of white flowers.

  Among rhinitis-based herbal medicines, beaks are obtained from dried roots of the ciraceae Yorigusa, although not limited thereto.

  When using rhinitis herbal medicine as an extract (extract), extraction solvents include water (including hot water), alcohols such as methanol, ethanol, isopropanol, ethylene glycol, glycerin, esters such as ethyl acetate, acetone, Ketones such as methyl ethyl ketone, nitriles such as acetonitrile, ethers such as diethyl ether and tetrahydrofuran, saturated hydrocarbons such as pentane, hexane, cyclopentane and cyclohexane, aromatic hydrocarbons such as toluene, dichloromethane, chloroform, etc. Halogenated hydrocarbons and other organic solvents such as dimethylformamide and dimethylsulfoxide (all of which may be water-containing) can be used as appropriate, and one or two arbitrary mixed liquids may be used. Among these solvents, water, ethanol, or a mixed solution thereof is preferable from the viewpoint of safety.

  The rhinitis crude drug extract may be a crude extract extracted from the whole plant or a necessary part of the plant as it is, a purified product thereof, a purified product, a concentrated product, or a synthetic product. A commercially available product can also be used. There are no particular limitations on the method for obtaining the rhinitis crude drug extract, and usual extraction methods, purification methods, concentration methods, synthesis methods, dry powdering methods, and the like are employed. Moreover, the extract of a rhinitis-based crude drug may satisfy the items listed in the 17th revision Japanese Pharmacopoeia.

  Rhinitis herbal extract may be used in liquid form, but if necessary, it can be concentrated by reducing or removing the liquid by performing drying treatment such as vacuum drying, freeze drying, spray drying, etc. A liquid, semi-solid, solid, or powdered product may be used.

  In the pharmaceutical composition of the present invention, the daily dose (dosage) of rhinitis herbal medicine is the amount of mequitazine, the type of rhinitis herbal medicine, the type and amount of other ingredients, the state of the user (weight, age, sex) , Symptoms, physical condition, etc.), and can be appropriately set according to the dosage form, etc., but is not limited, but from the viewpoint of more prominently exerting the effects of the present invention, the total amount expressed in terms of the active ingredient (plural types of rhinitis system) Including a case of containing a crude drug), it may be 300 to 13000 mg, preferably 500 to 12000 mg, more preferably 700 to 11000 mg, still more preferably 950 to 10000 mg, still more preferably 60 to 9000 mg, More preferably, it can be 1100 to 8000 mg, particularly preferably 1250 to 7500 mg, and most preferably 1400 to 7000 mg. .

  In addition, although not limited, the daily oral dose of Shinyi can be about 1 to about 5000 mg, more preferably about 50 to about 4000 mg, more preferably, expressed in terms of the drug substance equivalent. Preferably, it can be about 100 to about 3500 mg, particularly preferably about 150 to about 3500 mg, and most preferably about 200 to about 3000 mg. In addition, the daily oral dose of Shiny extract can be about 0.01 to about 2700 mg, more preferably about 0.1 to about 1800 mg, and still more preferably about 0.5 to about It can be 1500 mg, particularly preferably about 1 to about 1200 mg, most preferably about 3 to about 900 mg. Moreover, the daily oral dose of licorice can be about 5 to about 8000 mg, more preferably about 300 to about 7000 mg, more preferably about 500 to about 6000 mg, more preferably about 750 to about 5500 mg, more preferably about 950 to about 5000 mg, more preferably about 1100 to about 5000 mg, more preferably about 1500 to about 5000 mg, and particularly preferably about 2000 to about 5000 It can be 5000 mg, most preferably about 2500 to about 5000 mg. The daily dose of licorice extract can be about 150 to about 2100 mg, more preferably about 200 to about 1800 mg, still more preferably about 250 to about 1500 mg, particularly preferably It can be about 300 to about 1200 mg, most preferably about 350 to about 900 mg. In addition, the daily oral dose of saicin can be about 1 to about 5000 mg, more preferably about 50 to about 4000 mg, and more preferably about 100 to about 5000 when expressed in terms of bulk drug substance. It may be 3500 mg, particularly preferably about 150 to about 3500 mg, most preferably about 200 to about 3000 mg. Moreover, the daily oral dose of ginger can be about 1 to about 5000 mg, more preferably about 50 to about 4000 mg, more preferably about 100 to About 3500 mg, more preferably about 150 to about 3500 mg, more preferably about 200 to about 3000 mg, more preferably about 300 to about 3000 mg, more preferably about 500 to about 3000 mg, more preferably about 750 to about The amount may be about 3000 mg, more preferably about 900 to about 3000 mg, particularly preferably about 1200 to about 3000 mg, and most preferably about 1500 to about 3000 mg. In addition, the daily oral dose of mussel can be about 1 to about 5000 mg, more preferably about 50 to about 4000 mg, and more preferably about 100 to about 5000 when expressed in terms of bulk drug substance. It may be 3500 mg, particularly preferably about 150 to about 3500 mg, most preferably about 200 to about 3000 mg. In addition, the daily oral dose of Zenko can be about 1 to about 5000 mg, more preferably about 50 to about 4000 mg, and more preferably about 100 to about 5000 when expressed in terms of bulk drug substance. It may be 3500 mg, particularly preferably about 150 to about 3500 mg, most preferably about 200 to about 3000 mg. Further, the daily oral dose of juniper can be expressed as about 1 to about 5000 mg, more preferably about 50 to about 4000 mg, and more preferably about 100 to about It may be 3500 mg, particularly preferably about 150 to about 3500 mg, most preferably about 200 to about 3000 mg.

  In the present specification, “concentration of crude drug” means what is expressed as the weight (dry weight) of a crude drug (mixture of crude drugs) necessary to obtain the amount of its components. When an extract is used as a crude drug, the dry weight of the drug substance necessary for obtaining the amount of the extract becomes the drug substance equivalent amount. The daily dose may be divided into 1 to 6 times, preferably 1 to 3 times.

  The total content of rhinitis crude drugs may vary depending on the amount of mequitazine, the type of rhinitis crude drug, the type and amount of other ingredients, the user's condition (weight, age, symptoms, physical condition, etc.), and the dosage form. When the pharmaceutical composition is a solid preparation, it is usually 0.01 to 99% by weight, preferably 0.05 to 95% by weight, more preferably 0.1 to 90% by weight, based on the total amount of the pharmaceutical composition. Particularly preferred is 1 to 85% by weight. In addition, when the pharmaceutical composition is a liquid preparation, the total content of rhinitis herbal medicine is usually 0.01 to 80% by weight, preferably 0.05 to 70% by weight, more preferably, based on the total amount of the pharmaceutical composition. Is 0.1 to 60% by weight, particularly preferably 1 to 55% by weight. When the solid preparation includes a liquid preparation, it is usually 0.01 to 70% by weight, preferably 0.05 to 60% by weight, more preferably 0.1 to 50% by weight, based on the total amount of the liquid preparation. Particularly preferred is 1 to 50% by weight.

  In addition, the compounding ratio of mequitazine and nasal herbal medicine in the pharmaceutical composition of the present invention includes the type of rhinitis herbal medicine, the type and amount of other ingredients, the state of the user (weight, age, sex, symptoms, physical condition, etc.) , And can be appropriately set according to the dosage form, and is not limited, but from the viewpoint of exerting the effects of the present invention more remarkably, 1 to 7000 wt. Parts, preferably 10 to 6000 parts by weight, more preferably 25 to 5000 parts by weight, still more preferably 50 to 4000 parts by weight, even more preferably 60 to 3500 parts by weight, particularly preferably 75 to 3000 parts by weight, even more preferably. Can be from 75 to 2500 parts by weight, most preferably from 90 to 2000 parts by weight.

  Although not limited, Shini is 1 to 3000 parts by weight, preferably 3 to 3000 parts by weight, more preferably 5 to 2800 parts by weight, and still more preferably 10 to 2400 parts per million by weight of mequitazine. It can be in a proportion of parts by weight, more preferably 20 to 2000 parts by weight, particularly preferably 30 to 1800 parts by weight, still more preferably 50 to 1500 parts by weight, and most preferably 75 to 1300 parts by weight. In addition, licorice is 50 to 6000 parts by weight in terms of bulk drug substance, preferably 80 to 6000 parts by weight, more preferably 100 to 6000 parts by weight, still more preferably 250 to 6000 parts by weight, and even more based on 1 part by weight of mequitazine. Preferably 255-5000 parts by weight, particularly preferably 260-4000 parts by weight, more particularly preferably 270-3000 parts by weight, most preferably 280-2000 parts by weight, 290-1800 parts by weight, 300-1500 parts by weight, 300- The ratio can be 1200 parts by weight. From another point of view, licorice is 50 to 200 parts by weight, preferably 60 to 190 parts by weight, more preferably 70 to 180 parts by weight, and still more preferably 80 to 170 parts by weight in terms of bulk drug substance per 1 part by weight of mequitazine. It can also be made into the ratio of a weight part. Moreover, 1 to 3000 parts by weight, preferably 3 to 3000 parts by weight, more preferably 5 to 2800 parts by weight, still more preferably 10 to 2400 parts by weight, and even more based on 1 part by weight of mequitazine. The ratio is preferably 20 to 2000 parts by weight, particularly preferably 30 to 1800 parts by weight, still more preferably 50 to 1500 parts by weight, and most preferably 75 to 1300 parts by weight. Moreover, 1 to 3000 parts by weight, preferably 10 to 2400 parts by weight, more preferably 50 to 1500 parts by weight, more preferably 75 to 1300 parts by weight, and more preferably 75 to 1300 parts by weight of shochu as raw drug equivalent to 1 part by weight of mequitazine. More preferably, the ratio can be 100 to 1300 parts by weight, particularly preferably 120 to 1300 parts by weight, still more preferably 150 to 1300 parts by weight, and most preferably 200 to 1300 parts by weight. Moreover, from another viewpoint, 1 to 80 parts by weight, preferably 5 to 70 parts by weight, more preferably 10 to 60 parts by weight, and further preferably 15 to 15 parts by weight of shochu is 1 part by weight of mequitazine. It can also be a ratio of 50 parts by weight. In addition, 1 to 3000 parts by weight, preferably 3 to 3000 parts by weight, more preferably 5 to 2800 parts by weight, still more preferably 10 to 2400 parts by weight, and even more based on the amount of bulk drug based on 1 part by weight of mequitazine. The ratio is preferably 20 to 2000 parts by weight, particularly preferably 30 to 1800 parts by weight, still more preferably 50 to 1500 parts by weight, and most preferably 75 to 1300 parts by weight. Also, Zenko is 1 to 3000 parts by weight, preferably 3 to 3000 parts by weight, more preferably 5 to 2800 parts by weight, and even more preferably 10 to 2400 parts by weight, based on 1 part by weight of mequitazine. The ratio is preferably 20 to 2000 parts by weight, particularly preferably 30 to 1800 parts by weight, still more preferably 50 to 1500 parts by weight, and most preferably 75 to 1300 parts by weight. In addition, 1 to 3000 parts by weight, preferably 3 to 3000 parts by weight, more preferably 5 to 2800 parts by weight, still more preferably 10 to 2400 parts by weight, and even more from 1 to 3 parts by weight of mekazine. The ratio is preferably 20 to 2000 parts by weight, particularly preferably 30 to 1800 parts by weight, still more preferably 50 to 1500 parts by weight, and most preferably 75 to 1300 parts by weight.

  The pharmaceutical composition of the present invention may contain other physiologically active ingredients in addition to mequitazine and rhinitis herbal medicine, if desired.

Examples of such physiologically active components include: (1) antihistamine components (for example, istipendil hydrochloride, iproheptin hydrochloride, dipheterol hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, triprolidine hydrochloride hydrate, tripelenamine hydrochloride , Tondylamine hydrochloride, Promethazine hydrochloride, Metodirazine hydrochloride, Diphenhydramine salicylate, Carbinoxamine diphenyldisulfonate, Alimemazine tartrate, Diphenhydramine tannate, Diphenylpyraline theocrate, Carbinoxamine maleate, Chlorpheniramine maleic acid Salt, promethazine methylene disalicylate),
(2) Parasympathetic nerve blocking components (for example, belladonna total alkaloids, isopropamide iodide, duck extract, funnel extract, etc.),
(3) sympathomimetic components (such as methylephedrine, pseudoephedrine, phenylephrine, methoxyphenamine or salts thereof),
(4) Anti-inflammatory enzymes (eg lysozyme, bromelain, etc.)
(5) Glycyrrhizic acids (for example, glycyrrhizic acid or a salt thereof),
(6) xanthine derivatives (for example, sodium benzoate caffeine, caffeine hydrate, caffeine such as anhydrous caffeine),
Etc.

  These physiologically active ingredients may be free forms or salts.

  From the viewpoint of stably exhibiting the effects of the present invention, these physiologically active components include methylephedrine and its salts (such as methylephedrine hydrochloride), pseudoephedrine and its salts (such as pseudoephedrine hydrochloride), belladonna total alkaloids, glycyrrhizin At least one selected from the group consisting of an acid or a salt thereof (such as dipotassium glycyrrhizinate) and anhydrous caffeine is preferred.

  The pharmaceutical composition of the present invention can be, for example, a pharmaceutical product, a quasi-drug, or a raw material thereof [eg, pharmaceutical preparation, quasi-drug preparation].

  The pharmaceutical composition of the present invention can be prepared in various dosage forms as a solid preparation according to methods known to those skilled in the art. There are no particular limitations on the shape or size of the solid preparation. For example, the internal preparation includes tablets [orally disintegrating tablets, chewable tablets (chewable tablets), effervescent tablets, dispersible tablets, dissolving tablets, film-coated tablets, uncoated tablets. And sugar-coated tablets etc.], capsules [including hard capsules and soft capsules, etc.], granules [including foamed granules], powders, powders, fine granules, pills, oral tablets [troches] , Sublingual tablets, buccal tablets, adhesive tablets, gums, etc.], film agents, dry syrups, jellies, semi-solid oral preparations, confectionery agents [including candy, gummi, nougat agents, etc.] And so on. In addition, the pharmaceutical composition of the present invention can be prepared in various dosage forms as liquid preparations. For example, internal preparations include liquid preparations such as syrups, solutions and suspensions. Among these, it is preferable to use the pharmaceutical composition of the present invention for a solid preparation from the viewpoint of more prominently exerting the effects of the present invention, and it can be used for tablets, capsules, granules, powders, and film preparations. More preferably, it is more preferably used for tablets and capsules.

  The pharmaceutical composition of the present invention may contain appropriate additives depending on the dosage form. Such additives include binders (eg, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, etc.), excipients (eg, sucrose, lactose, starch, corn starch) , Crystalline cellulose, light anhydrous silicic acid, mannitol, sorbitol, etc.), lubricant (eg, sucrose fatty acid ester, stearic acid such as magnesium stearate and salts thereof, talc, etc.), disintegrant (eg, low substituted hydroxy) Propyl cellulose, crospovidone, croscarmellose sodium, etc.), foaming agent (eg, sodium bicarbonate), fluidizing agent (eg, sodium aluminate metasilicate, light anhydrous silicic acid, etc.) , Oily bases (for example, safflower oil, olive oil, corn oil, soybean oil, sesame oil, cottonseed oil, wheat germ oil and other vegetable oils; medium chain fatty acid triglycerides, etc.), aqueous bases (for example, Macrogol 400, glycerin, water Etc.), gel base (for example, carboxyvinyl polymer, gum), surfactant (for example, polysorbate 80, hydrogenated castor oil, glycerin fatty acid ester, sorbitan sesquioleate, propylene glycol fatty acid ester, sucrose fatty acid ester, etc. ), Suspending agents (eg beeswax and various surfactants, gum arabic, gum arabic powder, xanthan gum, soybean lecithin, etc.), dispersants, emulsifiers, stabilizers, buffers, solubilizers, pH adjusters, Preservatives (preservatives), antioxidants, sweeteners, sour agents, colorants, flavors, and And taste agent may be added as appropriate.

  Among these additives, from the viewpoint of stably exhibiting the effects of the present invention, crystalline cellulose, hydroxypropylcellulose, polyvinylpyrrolidone, croscarmellose sodium, magnesium stearate, polysorbate 80, glycerin fatty acid ester, white beeswax, And at least one selected from the group consisting of medium-chain fatty acid triglycerides.

  The pharmaceutical composition of the present invention can be produced by adopting a usual formulation method depending on the formulation form. For example, the above-mentioned components can be granulated (eg, extrusion granulation, fluidized bed granulation, spray drying granulation, etc.), dried, and sieved to produce granules. Using this, capsules or tablets can be produced by a conventional method. Also, for example, after each component is dissolved in an appropriate amount of purified water, the pH is preferably adjusted to 2-8, more preferably 2.5-7, still more preferably 3-6, and then the remaining purification. It can be produced by adjusting the volume by adding water. Here, it is preferable to employ a method in which mequitazine and rhinitis herbal medicine are sufficiently mixed.

[Apply]
In addition, the pharmaceutical composition of the present invention can be used for symptoms associated with rhinitis and rhinitis-related symptoms (nasal discharge (nasal discharge, runny nose, nasal discharge)), nasal congestion (nasal congestion), sneezing, sneezing, pruritus. Any pain, head weight (heavy head), nasal mucosal swelling, nasal congestion, nasal bleeding, and nasal mucosal atrophy or sclerosis, etc., may be indicated, including acute rhinitis and sinusitis, allergic Effective against rhinitis (including perennial allergic rhinitis and seasonal allergic rhinitis (eg, nasal inflammation symptoms of hay fever)). In particular, the pharmaceutical composition of the present invention is highly effective for rhinitis caused by viruses, bacterial infections, and allergens (such as mites, molds, house dust, air pollutants, and pollen). Although not limited, the pharmaceutical composition of the present invention may be a nasal discharge, nasal congestion, or sneezing due to allergic rhinitis, nasal discharge, nasal congestion or sneezing due to pollen, house dust, or acute rhinitis due to allergen, sinusitis, or It can be suitably used for allergic rhinitis. Although it is not limited, the pharmaceutical composition of the present invention can be suitably used for sticky nasal discharge, nasal discharge falling to the throat, nasal discharge from the outer nostril, stuffy breathing, and head-bogging symptoms. The pharmaceutical composition of the present invention can be used for internal use (for oral administration), for example.

  The pharmaceutical composition of the present invention can improve solubility in water when mequitazine and nasal herbal medicine coexist in the pharmaceutical composition. The present invention exhibits high solubility in water, so that the active ingredient is quickly dissolved from the pharmaceutical composition in the body (fast dissolution effect) and / or released quickly (fast release effect). Therefore, the drug absorbability in the body is improved, and it becomes possible to provide a pharmaceutical composition having high effects on mechatazine and nasal herbal medicine against acute rhinitis, allergic rhinitis, sinusitis and the like. Therefore, the pharmaceutical composition of the present invention is useful for at least one selected from the group consisting of acute rhinitis, allergic rhinitis, and sinusitis.

  The dosage of the pharmaceutical composition of the present invention is appropriately set according to the form, administration method, administration purpose, and age, weight, symptom, and physical condition of the administration subject of the composition, and is not constant. In addition, the pharmaceutical composition of the present invention may be administered once or divided into several times per day within a desired dose range, and administered before meals, between meals, after meals, or simultaneously with meals. May be. In addition, the term “administration” in the present specification is intended to include “taking”.

  The pharmaceutical composition of the present invention can be administered usually 1 to 6 times a day, preferably 1 to 3 times a day. Therefore, the pharmaceutical composition of the present invention for a single administration preferably contains the above-mentioned daily dose divided by the number of administrations per day. The pharmaceutical composition of the present invention is preferably administered 1 to 3 times a day because of its improved solubility in water and excellent drug fast solubility and / or rapid release properties. It can be used twice a day or three times a day.

  The pharmaceutical composition of the present invention may be a single preparation obtained by simultaneously formulating mequitazine and a nasal herbal medicine, or may be a combination of two kinds of preparations obtained separately. In either case, the effects of the present invention can be achieved.

[Method for imparting water-dispersibility and / or solubility-improving action to pharmaceutical composition]
According to the present invention, it is also possible to provide a method for imparting water-dispersibility and / or solubility-improving action to a pharmaceutical composition, including coexistence of mequitazine and a nasal herbal medicine in the pharmaceutical composition. . The amount of mequitazine, the type and amount of rhinitis herbal medicine, and the type and amount of other components are the same as in the case of the above [pharmaceutical composition].

  EXAMPLES Next, the present invention will be specifically described with reference to examples, but the present invention is not limited to the following examples.

[Test Example 1: Dispersibility evaluation (1)]
Each component shown in Table 1 was mixed according to the prescription and charged into a 20 mL volumetric flask. Purified water was added to make a 20 mL test solution. After mixing the volumetric flask 30 times by inversion, the volumetric flask was allowed to stand, and at room temperature (24 ° C.), the state of adhesion or precipitation of the solid matter on the liquid surface and bottom after 120 minutes was visually observed. Shiny extract was used that satisfies the Shinyi items listed in the 17th revision of the Japanese Pharmacopoeia (the same shall apply hereinafter). The results are also shown in Table 1.

  As shown in Table 1, in Comparative Example 1-1, solid matter was adhered near the liquid surface. In Example 1-1 and Example 1-2 containing mequitazine and Shiny extract, which is a rhinitis herbal medicine, no solid matter was observed. On the bottom surface, in Comparative Example 1-1, solid matter was settled. In Example 1-1 and Example 1-2, no white precipitate derived from mequitazine was observed. From these facts, it was confirmed that the dispersibility of mequitazine in water was improved by adding a rhinitis herbal medicine. Accordingly, a pharmaceutical composition containing mequitazine and a nasal herbal medicine is a composition that is easy to disperse in water (fast dissolution effect), has excellent drug release in the body (fast release effect), and is easily absorbed in the body. It became clear.

[Test Example 2: Solubility evaluation (1)]
Each component shown in Table 2 and Table 3 was mixed according to the formulation, and purified water was added to make a 20 mL test solution. After the test solution was stirred at 800 rpm for 30 minutes, the content of mequitazine dissolved in purified water was measured by a liquid chromatography method according to the following analysis conditions. Each herbal extract used what satisfies the items listed in the 17th revised Japanese Pharmacopoeia (the same applies hereinafter).

Analysis conditions Detector: UV absorption photometry (wavelength 254 nm)
Column: inner diameter 4.0 mm, length 100 mm, particle diameter 3 μm
Column temperature: constant temperature around 30 ° C. Mobile phase: liquid obtained by dissolving 1 mL of trifluoroacetic acid in 1000 mL and acetonitrile liquid mixed in 3: 2 Flow rate: adjusted so that the retention time of mequitazine is about 5 minutes (0 .5min / min)

Next, the degree of dissolution improvement was calculated by the following formula 1.
[Formula 1] Degree of improvement in dissolution = (mequitazine content of test solution of example) / (mequitazine content of test solution of corresponding comparative example)
Here, the corresponding comparative example is a test solution that contains the same amount of mequitazine as in the examples and does not contain a rhinitis herbal medicine. The results are shown in Tables 2 and 3.

  In Table 2, in Comparative Examples 2-1 and 2-2, mequitazine hardly dissolved in purified water. As shown in Tables 2 and 3, surprisingly, it was found that the solubility of mequitazine is markedly improved by coexisting with nasal herbal medicine (Example 2-1 to Example 2). -11). Accordingly, it has been clarified that a pharmaceutical composition containing mequitazine and a rhinitis-based crude drug is a composition that is excellent in the bioabsorbability of the drug (high absorbability) and easily exhibits the effect of the drug in vivo.

[Production example]
Using known techniques, pharmaceutical compositions were prepared for the formulation examples listed in Tables 4-5. The weight in the table is the daily dose. Formulation Examples 1 to 5 were 250 mg tablets per tablet, and 3 tablets were taken per day. Formulation Examples 6-10 prepared 267 mg of the contents (slurry) per soft capsule, encapsulated with a base of the capsule outer film to form a soft capsule, and took one capsule three times a day. . The numbers in parentheses in the table indicate the amount equivalent to the drug substance.

Claims (8)

  A pharmaceutical composition comprising mequitazine and a nasal herbal medicine.   2. The pharmaceutical composition according to claim 1, wherein the rhinitis herbal medicine is at least one selected from the group consisting of Shinyi, licorice, saishin, ginger, mussel, zenko, juniper, and extracts thereof.   The pharmaceutical composition according to claim 1 or 2, comprising 3 to 7 mg of the mequitazine as a daily dose for an adult.   The pharmaceutical composition according to any one of claims 1 to 3, wherein the rhinitis herbal medicine is contained in an amount of 1 to 7000 parts by weight in terms of bulk drug based on 1 part by weight of the mequitazine.   The pharmaceutical composition according to any one of claims 1 to 4, further comprising at least one selected from the group consisting of stearic acid and salts thereof.   The pharmaceutical composition according to any one of claims 1 to 5, which is a solid preparation.   The pharmaceutical composition according to any one of claims 1 to 6, which is at least one selected from the group consisting of acute rhinitis, allergic rhinitis, and sinusitis. The pharmaceutical composition according to any one of claims 1 to 7, which is fast-dissolving and / or fast-releasing.