JP2017048186A - Pharmaceutical composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a pharmaceutical composition that has excellent smooth liquid blending into capsule coating, and is suitable for producing soft capsule agent.SOLUTION: A pharmaceutical composition contains: (A) at least one selected from the group consisting of fexofenadine, epinastine, loratadine, olopatadine, emedastine, cetirizine, levocetirizine and salt thereof and magnoliae extract; (B) at least one selected from the group consisting of surfactant and polyalcohol; and (C) hydrophobic base agent. Furthermore, a method for imparting improving effect of smooth liquid blending for capsule coating to the pharmaceutical composition includes a step of allowing the component (A), the component (B) and the component (C) to coexist in the pharmaceutical composition.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a pharmaceutical composition.

  As allergic drugs, chemical mediator release inhibitors, antihistamines, leukotriene antagonists and other drugs having various mechanisms are known. Among allergic drugs, various drugs have been developed as antihistamines for a long time. Drugs called first-generation antihistamines have high fat solubility, and thus pass through the blood-brain barrier and act sedatively in the hypothalamus to cause sleepiness. Second-generation antihistamines have been developed as drugs with few side effects related to sleepiness. Among them, fexofenadine has little sedation and is widely used in clinical practice. Fexofenadine is mainly used as fexofenadine hydrochloride in tablets (Non-patent Document 1). As other second generation antihistamines, epinastine, loratadine, olopatadine, emedastine, and cetirizine are known.

  In addition, for allergic symptoms such as hay fever and rhinitis, treatment with herbal medicines such as hot pepper extract has been performed for a long time.

  Capsules, which are one type of pharmaceutical product, are excellent in portability and are preferred by users. Soft capsules are smooth and easy to swallow and are preferred by users. As a method for producing a general soft capsule, a flat plate type, a rotary method, and a seamless method are exemplified.

  In the production of the rotary method (punching method), a sheet-like capsule film sandwiches a flowing filling content and forms a capsule shape along a hole of a rotating cylindrical mold. On the other hand, in the production of the seamless method (drop method), the capsule coating composition and the contents are simultaneously ejected from concentric multiple nozzles to form a seamless capsule shape.

"Allegra Tablets 30mg / 60mg, Allegra OD Tablets 360mg, Allegra Dry Syrup 5%", Drug Interview Form, Revised January 2015 (21st Edition)

  Regardless of the manufacturing method, capsules, especially soft capsules, may cause unevenness in the contents of filling, bubble penetration, liquid leakage, etc. There is a fear. As a result, the production efficiency may be reduced, and the action and quality uniformity of the pharmaceutical product may be impaired.

  Accordingly, an object of the present invention is to provide a pharmaceutical composition in which the liquid compatibility between the capsule film and the filled contents is good, the production efficiency is good, and the quality is constant.

  The present inventors have (A) at least one selected from the group consisting of fexofenadine, epinastine, loratadine, olopatadine, emedastine, cetirizine, levocetirizine and a salt thereof, and a spicy extract (hereinafter referred to as ( A composition) containing (A) component) and (C) hydrophobic base (hereinafter also referred to as component (C) in this specification) increases the dynamic contact angle with the capsule film, I found a new problem that the familiarity would worsen. Further, the present inventors have (B) at least one selected from the group consisting of a surfactant and a polyhydric alcohol (hereinafter also referred to as component (B) in this specification), and (C) a hydrophobic group. When the coexisting agent is present, the dynamic contact angle is increased, and it has been found that there is a problem that even in this combination, the liquid compatibility becomes worse. As a result of intensive investigations by paying attention to these problems, the present inventors effectively improve the liquid familiarity by coexisting the component (A), the component (B), and the component (C). As a result, the present invention has been completed.

That is, the present invention
[1] (A) at least one selected from the group consisting of fexofenadine, epinastine, loratadine, olopatadine, emedastine, cetirizine, levocetirizine and salts thereof, and a spicy extract;
(B) at least one selected from the group consisting of a surfactant and a polyhydric alcohol;
(C) a pharmaceutical composition containing a hydrophobic base;
[2] The pharmaceutical composition according to [1] above, wherein the hydrophobic base (C) is an oil or fat, a wax or a fat-soluble vitamin;
[3] The pharmaceutical composition according to the above [1] or [2], which is a liquid pharmaceutical composition;
[4] A capsule in which the pharmaceutical composition according to [1] to [3] is filled in a capsule film;
[5] The pharmaceutical composition according to the above [1] to [3], which is rapidly soluble and / or rapidly released;
[6] (A) at least one selected from the group consisting of fexofenadine, epinastine, loratadine, olopatadine, emedastine, cetirizine, levocetirizine and salts thereof, and a spice extract;
(B) at least one selected from the group consisting of a surfactant and a polyhydric alcohol;
(C) A method of imparting a liquid conformity improving action to a capsule film to the pharmaceutical composition, including coexisting a hydrophobic base with the pharmaceutical composition; and the like.
In another embodiment, the present invention provides (A) at least one selected from the group consisting of (A) fexofenadine, epinastine, loratadine, olopatadine, emedastine, cetirizine, levocetirizine and a salt thereof, and a hot pepper extract,
(B) at least one selected from the group consisting of a surfactant and a polyhydric alcohol;
(C) It is also possible to provide a method for producing a solid preparation characterized in that a hydrophobic base coexists in a pharmaceutical composition.

  In the pharmaceutical composition of the present invention, (A) at least one selected from the group consisting of fexofenadine, epinastine, loratadine, olopatadine, emedastine, cetirizine, levocetirizine and salts thereof, and a spicy extract, and (B) interface By containing at least one selected from the group consisting of an activator and a polyhydric alcohol and (C) a hydrophobic base, it is possible to effectively improve the liquid compatibility with the capsule film. In addition, the pharmaceutical composition of the present invention improves the dispersibility in water by allowing the components (A), (B), and (C) to coexist, thereby rapidly dissolving and rapidly releasing the drug. Excellent in properties.

It is a photograph which shows the dispersion state with respect to water by making (A) component, (B) component, and (C) component coexist.

[Pharmaceutical composition]
The pharmaceutical composition of the present invention comprises:
(A) at least one selected from the group consisting of fexofenadine, epinastine, loratadine, olopatadine, emedastine, cetirizine, levocetirizine and salts thereof, and a hot pepper extract;
(B) at least one selected from the group consisting of a surfactant and a polyhydric alcohol;
(C) a hydrophobic base.

[(A) component]
(RS) -2- [4- [1-hydroxy-4- [4- (hydroxy-diphenyl-methyl) -1-piperidyl] butyl] phenyl] -2-methyl-propion (generic name fexofenadine), ( ±) -3-amino-9,13b-dihydro-1H-dibenz [c, f] imidazo [1,5-a] azepine (generic name epinastine), ethyl 4- (8-chloro-5,6-dihydro- 11H-benzo [5,6] cyclohepta [1,2-b] pyridine-11-ylidine) -1-piperidinecarboxylate (generic name loratadine), {(11Z) -11- [3- (dimethyl Amino) -propylidene] -6,11-dihydrodibenzo [b, e] oxepin-2-yl} acetic acid (generic name olopatadine), 1- (2-ethoxyethyl) -2-[(hexahydro-4- Til-1H-1,4-diazepine) -1-yl] -1H-benzimidazole (generic name emedastine), 2- [2- [4- [α- (4-chlorophenyl) benzyl] piperazino] ethoxy] acetic acid ( The generic name cetirizine) and their salts are known compounds as second generation antihistamines. (A) A component can be obtained with a commercial item or can be manufactured by a well-known manufacturing method. The component (A) having a piperidine / piperazine skeleton is fexofenadine, cetirizine, levocetirizine and salts thereof, and the component (A) having a tricyclic structure is epinastine, loratadine, olopatadine and salts thereof The component (A) having a bicyclic structure composed of a monocyclic ring and a heterocyclic ring containing nitrogen is emedastine and a salt thereof.

  Among the components (A), the salt of fexofenadine, epinastine, loratadine, olopatadine, emedastine or cetirizine, levocetirizine is not particularly limited as long as it is a pharmaceutically, pharmacologically or physiologically acceptable salt. Of the salts of fexofenadine, epinastine, loratadine, olopatadine, emedastine or cetirizine, the compound having an optical isomer may be either R-form or S-form, or an optically separated one may be used. A racemate may be used. Although not limited, for example, levocetirizine is known as an optical isomer of cetirizine or a salt thereof, and levocetirizine hydrochloride is preferably used.

  In the present specification, the pharmaceutically, pharmacologically or physiologically acceptable salt specifically includes an organic acid salt, an inorganic acid salt, a salt with an organic base, or a salt with an inorganic base. . Examples of organic acid salts include monocarboxylic acid salts such as acetate, trifluoroacetate, butyrate, palmitate, and stearate; fumarate, maleate, succinate, malonate, and the like. Examples thereof include polyvalent carboxylates; oxycarboxylates such as lactate, tartrate and citrate; and organic sulfonates such as methanesulfonate, toluenesulfonate and tosylate. Examples of the inorganic acid salt include hydrochloride, sulfate, nitrate, hydrobromide, and phosphate. Examples of the salt with an organic base include salts with organic amines such as methylamine, triethylamine, triethanolamine, diethanolamine, morpholine, piperazine, pyrrolidine, tripyridine, picoline, and ethylenediamine. Examples of the salt with an inorganic base include various salts such as an ammonium salt; an alkali metal such as sodium or potassium; an alkaline earth metal such as calcium or magnesium; and a salt with a metal such as aluminum. These fexofenadine, epinastine, loratadine, olopatadine, emedastine, cetirizine or levocetirizine salts may be used alone or in any combination of two or more. These salts may include solvates or hydrates of the salts. Although not limited, a preferred pharmaceutically, pharmacologically or physiologically acceptable salt of fexofenadine, epinastine, olopatadine, cetirizine, or levocetirizine is the hydrochloride salt, known as fexofenadine hydrochloride . A preferred pharmaceutically, pharmacologically or physiologically acceptable salt of emedastine is fumarate, known as emedastine fumarate (emedastine fumarate).

  Among the components (A), the hot pepper extract is obtained by extracting from hot pepper. Although not limited, the hot pepper is obtained by drying the flower buds of magnoliaceae plants such as magnolia, humoclen, shimokureen, kobushi, tamashiba, or other related plants. The spicy extract may be a crude extract extracted from spicy sprout, or may be a purified product, a concentrated product, a product obtained by synthesis, or a commercially available product. Pepper extract that has been subjected to a concentration treatment is preferred. The method for obtaining the hot pepper extract is not particularly limited, and usual extraction methods, purification methods, concentration methods, synthesis methods, dry powdering methods, and the like are employed. Moreover, the hot pepper extract may satisfy the item of Shini listed in the 17th revision Japanese Pharmacopoeia.

  In the present invention, this extract may be used in a liquid form, and if necessary, the liquid content may be reduced or removed by performing a drying process such as reduced pressure drying, freeze drying, spray drying or the like. May be used in the form of a concentrated liquid, semi-solid, solid, or powder.

  Although not limited, the spicy extract includes magnoflorin, coclaurine, uzilin, reticuline, and the like. The components contained in these hot pepper extracts have at least three or more ring structures like the other components (A). Magnoflorin has a tricyclic structure. Coclaurine, euzirin and reticuline have a bicyclic structure consisting of a monocyclic ring and a nitrogen-containing heterocyclic ring.

  In the pharmaceutical composition of the present invention, the component (A) can be used alone or in combination of two or more. Although not limited, in the case where a spicy extract is used as the component (A), one kind may be used alone from the viewpoint of remarkably exhibiting the effects of the present invention, and fexofenadine, epinastine, loratadine, olopatadine, emedastine , Cetirizine, levocetirizine or a salt thereof can be used.

  In addition, in the pharmaceutical composition of the present invention, the combination ratio in the case where the hot pepper extract and fexofenadine, epinastine, loratadine, olopatadine, emedastine, cetirizine, levocetirizine or a salt thereof is used in combination is as follows: Although it can be appropriately set according to the type of component (B) and / or component (C), the type and amount of other components, and the dosage form of the pharmaceutical composition of the present invention, the effects of the present invention are more prominently exhibited. From the viewpoint of making fexofenadine, epinastine, loratadine, olopatadine, emedastine, cetirizine, levocetirizine, or a salt thereof, 0.01 to 250 parts by mass, preferably 0.05 to 200 parts by mass, more preferably 0.1 to 120 parts by mass, and even more preferably 0.5 to 60 parts by mass. .

  The dose (dosage) of the component (A) in the pharmaceutical composition of the present invention is the type and amount of the component (B) and component (C), the type and amount of other components, the condition of the user (weight, age, Gender, symptom, physical condition, etc.), and the dosage form of the pharmaceutical composition of the present invention can be appropriately set, and is not limited, but from the viewpoint of more prominently exerting the effects of the present invention, it is usually per day. The oral dose can be about 30 to about 240 mg, more preferably about 10 to about 200 mg, more preferably about 20 to about 160 mg, and particularly preferably about 30 to about 240 mg as fexofenadine hydrochloride. It can be about 140 mg, most preferably about 60 to about 120 mg. The oral dose per day can be about 3 to about 60 mg as epinastine hydrochloride, more preferably about 4 to about 50 mg, still more preferably about 6 to about 40 mg, particularly preferably. About 8 to about 30 mg, most preferably about 10 to about 20 mg. The daily oral dose can be about 1 to about 50 mg as loratadine, more preferably about 2 to about 40 mg, more preferably about 3 to about 30 mg, and particularly preferably about It can be 4 to about 20 mg, most preferably about 5 to about 10 mg. The daily oral dose can be about 0.5 to about 25 mg as olopatadine hydrochloride, more preferably about 1 to about 20 mg, and still more preferably about 1.5 to about 15 mg. Particularly preferably, it may be about 2 to about 10 mg, most preferably about 2.5 to about 5 mg. In addition, the daily oral dosage can be about 0.4 to about 12 mg, more preferably about 0.6 to about 10 mg, and still more preferably about 0.8 to about emedastine fumarate. It can be about 8 mg, particularly preferably about 1 to about 6 mg, most preferably about 2 to about 4 mg. Further, the daily oral dose can be about 1 to about 60 mg as cetirizine hydrochloride, more preferably about 2 to about 50 mg, still more preferably about 3 to about 40 mg, particularly preferably. About 4 to about 30 mg, most preferably about 5 to about 20 mg. The daily oral dose can be about 1 to about 50 mg as levocetirizine hydrochloride, more preferably about 2 to about 40 mg, still more preferably about 3 to about 30 mg, and particularly preferably About 4 to about 20 mg, most preferably about 5 to about 10 mg. The daily oral dose can be about 1 to about 400 mg, more preferably about 3 to about 350 mg, more preferably about 5 to about 300 mg, and particularly preferably as a hot pepper extract. From about 10 to about 280 mg, and most preferably from about 20 to about 250 mg. The daily oral dose of the hot pepper extract can be about 10 to about 5000 mg, more preferably about 40 to about 4200 mg, more preferably about 70 to about 70 mg when expressed in terms of bulk drug substance. It can be 3800 mg, particularly preferably about 150 to about 3500 mg, most preferably about 300 to about 3000 mg. In the present specification, “concentration of crude drug” means that the amount of hot pepper extract is expressed as the amount of raw drug (mixture of crude drugs) necessary for preparing the hot pepper extract. The daily dose may be divided into 1 to 3 times.

  The content of the component (A) in the pharmaceutical composition of the present invention can be appropriately set according to the dosage form and the number of doses so as to be the above dose, and is not limited, for example, based on the total amount of the pharmaceutical composition 1 to 90% by mass, preferably 5 to 60% by mass, and more preferably 10 to 50% by mass.

[Component (B)]
At least one selected from the group consisting of (B) a surfactant and a polyhydric alcohol in the pharmaceutical composition of the present invention is compatible with the capsule film of the pharmaceutical composition by coexisting with the component (C) described later. This causes the problem of lowering. On the other hand, (B) component is a component which can improve the liquid familiarity with respect to the capsule membrane | film | coat of pharmaceutical composition by coexisting with (A) component and (C) component.

  Among the components (B) in the pharmaceutical composition of the present invention, the surfactant is a nonionic surfactant, a cationic surfactant, an anionic surfactant, an amphoteric, depending on the difference in ionization of the hydrophilic group. Differentiated from surfactants. Such a surfactant is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutical) or physiologically acceptable, and includes a nonionic surfactant, an amphoteric surfactant, and an anion. Either a cationic surfactant or a cationic surfactant may be used. Although not limited, the surfactant is preferably a nonionic surfactant or an amphoteric surfactant, and more preferably a nonionic surfactant, from the viewpoint of remarkably exhibiting the effects of the present invention.

In the present invention, any nonionic surfactant can be used as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. For example, polyoxyethylene (hereinafter also referred to as POE). ) -Polyoxypropylene (hereinafter also referred to as POP) block copolymer (eg, poloxamer such as Poloxamer 407, Poloxamer 235, Poloxamer 188); POE-POP block copolymer adduct of ethylenediamine such as poloxamine; POE monolaurate (20 ) Sorbitan (polysorbate 20), monooleic acid POE
(20) POE sorbitan fatty acid esters such as sorbitan (polysorbate 80), POE sorbitan monostearate (polysorbate 60), POE sorbitan tristearate (polysorbate 65); propylene glycol fatty acid esters such as propylene glycol monostearate; POE (5) Hardened castor oil, POE (10) hardened castor oil, POE (20) hardened castor oil, POE (40) hardened castor oil, POE (50) hardened castor oil, POE (60) hardened castor oil, POE (100 ) Hydrogenated castor oil, POE (3) castor oil, POE (10) castor oil, POE castor oil such as POE (35) castor oil; POE alkyl ethers such as POE (9) lauryl ether; POE (20) POP (4 ) POE / POP alkyl ethers such as cetyl ether; POE alkyl phenyl ethers such as OE (10) nonylphenyl ether; polyethylene glycol monostearate such as polyoxyl 40 stearate; propylene glycol fatty acid esters such as propylene glycol monostearate; sucrose fatty acid esters; glycerin such as glyceryl monostearate Fatty acid esters; sorbitan fatty acid esters such as sorbitan sesquioleate, sorbitan monostearate, sorbitan monooleate, sorbitan trioleate, and the like. In addition, the number in a parenthesis shows the average addition mole number of POP or POE. Although not limited, POE castor oil, propylene glycol fatty acid ester, glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, among these nonionic surfactants, from the viewpoint of exerting the effects of the present invention more remarkably And at least one selected from the group consisting of POE hydrogenated castor oil, propylene glycol monostearate, glyceryl monostearate, sucrose fatty acid ester, POE sorbitan fatty acid ester, sorbitan fatty acid ester More preferably, POE (60) hydrogenated castor oil, propylene glycol monostearate, glyceryl monostearate, sucrose stearate, polysorbate 80, sorbitan sesquioleate At least one, more preferably is selected Ri, glycerin fatty acid esters, propylene glycol fatty acid esters and / or polysorbate 80, more preferably. These nonionic surfactants may be synthesized and used by a known method, or commercially available products may be obtained and used. A nonionic surfactant can be used individually or in combination of 2 or more types.

  In the present invention, the HLB value of the nonionic surfactant is not particularly limited, but can be set to 7 or more from the viewpoint of exhibiting the effects of the present invention more remarkably. Preferably they are HLB10-20, More preferably, they are HLB12-19.5, More preferably, they are HLB13-18. In addition, the HLB value of the nonionic surfactant used in the present invention is not particularly limited, but it can be less than 7 from a different viewpoint. In this case, HLB is preferably 1.5 to 6.5. Preferably it is 2-6.5, More preferably, it is 2.5-6. The HLB value is a value generally used in the art for evaluating the properties of a nonionic surfactant, and is also referred to as a hydrophilic-lipophilic balance. The HLB value is generally determined as a ratio of the hydrophilic portion in the whole molecule, and those having a small HLB value tend to have high lipophilicity and those having a high HLB value tend to have high hydrophilicity.

  Specific examples of amphoteric surfactants include lecithins such as soybean lecithin and egg yolk lecithin, alkyldiaminoethylglycine or a salt thereof (for example, hydrochloride, etc.), and the like.

  Specific examples of the cationic surfactant include benzalkonium chloride and benzethonium chloride.

  Specific examples of the anionic surfactant include alkylbenzene sulfonate, alkyl sulfate, polyoxyethylene alkyl sulfate, aliphatic α-sulfomethyl ester, α-olefin sulfonic acid and the like.

  Of the component (B) in the pharmaceutical composition of the present invention, the polyhydric alcohol refers to an alcohol having two or more hydroxyl groups in the molecule as generally understood by those skilled in the art.

  Any polyhydric alcohol can be used in the present invention as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Examples of the polyhydric alcohol include linear alcohols such as glycerin, propylene glycol, ethylene glycol, diethylene glycol, and polyethylene glycol (Macrogol 200, 400, 1500, 4000, 6000) or lactose, maltose, fructose, sorbitol, maltitol, mannitol. Sugar alcohols such as xylitol and trehalose. Of these polyhydric alcohols, linear alcohols or sugar alcohols are preferred from the viewpoint of more prominently exerting the effects of the present invention, and are selected from the group consisting of glycerin, propylene glycol, polyethylene glycol, ethylene glycol, sorbitol, and xylitol. At least one selected from the group consisting of glycerin, propylene glycol, polyethylene glycol, sorbitol, and xylitol is more preferable, glycerin, sorbitol, and polyethylene glycol are more preferable, and sorbitol and polyethylene glycol are particularly preferable. . These polyhydric alcohols may be synthesized and used by a known method, or commercially available products may be obtained and used. Polyhydric alcohols can be used alone or in combination of two or more.

  In the pharmaceutical composition of the present invention, the content of component (B) is the type and amount of component (A) and component (C), the type and amount of other components, and the patient's condition (weight, age, sex, symptom) , Physical condition, etc.), and the dosage form of the pharmaceutical composition of the present invention, and the like. Although not limited, from the viewpoint of more prominently exerting the effects of the present invention, the total amount of component (B) 0.1-80 mass% with respect to the composition whole quantity, Preferably it is 1-60 mass%, More preferably, it is 2-40 mass%, Most preferably, it can be 4-20 mass%.

  Moreover, the compounding ratio of (A) component and (B) component in the pharmaceutical composition of this invention is the kind of (A) component and (B) component, the kind and quantity of another component, and the pharmaceutical composition of this invention. Although it can set suitably according to the dosage form etc. of a thing, from a viewpoint of exhibiting the effect of this invention more notably, the total amount of (B) ingredient is 0.005-150 to 1 mass part of (A) ingredient. It is 0.01 mass part, Preferably, it is 0.01-100 mass part, More preferably, it is 0.05-60 mass part, More preferably, it can be 0.1-20 mass part.

[Component (C)]
The (C) hydrophobic base in the pharmaceutical composition of the present invention causes a problem that the compatibility of the pharmaceutical composition with the capsule film is reduced by coexisting with the component (A). Moreover, (C) hydrophobic base can also reduce the liquid familiarity with respect to the capsule film of a pharmaceutical composition also by coexisting with (B) component. On the other hand, the component (C) is a component that can improve liquid familiarity to the capsule film of the pharmaceutical composition by coexisting with the component (A) and the component (B). Moreover, the dispersibility with respect to water can be improved when (A) component, (B) component, and (C) component coexist in a pharmaceutical composition. The present invention exhibits high dispersibility in water, whereby 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 a high effect on bronchial asthma, allergic rhinitis, acute rhinitis, sinusitis and the like of component (A).

  The hydrophobic base is a hydrophobic base that disperses at least one of component (A) and component (B), preferably all of component (A) and component (B). Here, “hydrophobic” specifically means that the solubility of water in the “hydrophobic base” is 10 g / 100 g or less, preferably 1 g / 100 g or less, more preferably 0.1 g / 100 g or less. It means that. This solubility can be measured according to the solubility test described in the 16th revised Japanese Pharmacopoeia General Rules.

  The hydrophobic base in the present invention is not particularly limited. However, as long as it is liquid at 60 ° C. (preferably 37 ° C., more preferably 20 ° C.), the hydrophobic base is usually used as a soft capsule filling solution. preferable.

  In the present invention, any hydrophobic base can be used as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. For example, oils and fats, waxes, fat-soluble vitamins, carbonized Hydrogen etc. are mentioned.

  In the present specification, oil and fat means a compound in which a fatty acid is ester-bonded to a glycerin skeleton, that is, a glyceride as a main component. Fats and oils include, but are not limited to, castor oil, cottonseed oil, soybean oil, camellia oil, olive oil, sesame oil, falling raw oil, corn oil, coconut oil, rapeseed oil, wheat germ oil, safflower oil, sunflower oil, safflower Vegetable oils such as oil, perilla oil, hydrogenated oil, cacao butter; animal fats such as pork, beef tallow, milk and liver oils stabilized by hydrogenation of coconut oil; mineral oils such as silicone oil; medium chain fatty acid triglycerides And functional oils such as long-chain fatty acid triglycerides.

  Functional fats and oils are not limited, but short-chain fatty acids having 2 to 4 carbon atoms, medium-chain fatty acids having 5 to 12 carbon atoms, or fatty acids having a longer chain than 12 carbon atoms are mono-deca. The compound which carried out the ester bond to glycerol is mentioned. Short chain fatty acids include butyric acid, etc., medium chain fatty acids include valeric acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, lauric acid, etc., and long chain fatty acids include myristic acid. Acid, pentadecylic acid, palmitic acid, palmitoleic acid, margaric acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, linolenic acid, arachidic acid, arachidonic acid, behenic acid, lignoceric acid, nervonic acid, serotic acid, montanic acid, Examples include melicic acid.

  In this specification, wax refers to an ester of a higher fatty acid and a higher alcohol. Examples of waxes include, but are not limited to, beeswax, white beeswax, whale wax, carnauba wax, lanolin and the like.

  In the present specification, the fat-soluble vitamins include vitamin A, vitamin D, vitamin E, vitamin K, vitamin C ester and the like. Specifically, retinol derivatives such as retinol, acetic acid retinol, retinol palmitate, retinal, retinoic acid, methyl retinoic acid, ethyl retinoic acid, retinoic acid retinol, vitamin A oil, vitamin A fatty acid ester, α-carotene, β- Caroten, γ-carotene, δ-carotene, lycopene, zeaxanthin, cryptoxanthine, astaxanthin, echinenone and other vitamin A (including provitamin A and carotenoid), methyl hesperidin, ergocalciferol, cholecalciferol, 1,25 -Vitamin Ds (including provitamin Ds) such as dihydroxycholecalciferol, 7-dehydrocholesterol, ergosterol or derivatives thereof, dl-α-tocopherol, d-α-tocopherol, β- Tocopherol, γ-tocopherol, dl-δ-tocopherol, d-δ-tocopherol, α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol, α-tocolinate, β-tocolinate, γ-tocolinate, δ-tocolinate And derivatives thereof, and vitamins E such as salts thereof, phylloquinone, farnoquinone, menaquinone, menadione, etc., lauryl ascorbate, stearyl ascorbate, myristyl ascorbate, palmityl ascorbate, ascorbyl tetra-2-hexyldecanoate And vitamin C esters.

  Hydrocarbons include, but are not limited to, squalene, squalane, yellow petrolatum, white petrolatum, heavy liquid paraffin, light liquid paraffin, semi-liquid paraffin, liquid isoparaffin and the like.

  Among these (C) components, by coexisting with the (A) component and the (B) component, from the viewpoint of more remarkably improving the liquid familiarity to the capsule film of the pharmaceutical composition, fats and oils, waxes And fat-soluble vitamins, and as fats and oils, functional fats and / or vegetable fats and oils are more preferred, fats and oils containing triglycerides are more preferred, medium chain fatty acid triglycerides, corn oil, soybean oil, At least one selected from the group consisting of safflower oil and olive oil is more preferred, with medium chain fatty acid triglycerides, soybean oil and / or safflower oil being particularly preferred. In the present specification, the medium chain fatty acid triglyceride refers to a glycerin triester of a fatty acid having 4 to 12 carbon atoms, and includes a mixture mainly composed of fatty acid triglycerides having those carbon atoms. Although not limited, what has fatty acid triglycerides, such as C8 (caprylic acid) and 10 (capric acid), as a main component is mentioned. These can be obtained by hydrolyzing coconut oil, palm kernel oil, etc., then refining and recombining, or synthetic products. From another point of view, the component (C) is preferably wax as waxes, more preferably white beeswax. From another point of view, component (C) is preferably vitamin E as the fat-soluble vitamins, more preferably tocopherols, dl-α-tocopherol, d-α-tocopherol, d-δ-tocopherol. Dl-α-tocopherol acetate, d-α-tocopherol acetate and / or tocopherol calcium succinate are more preferred.

  Specific products (trade names) of medium chain fatty acid triglycerides include, for example, miglyol (manufactured by Mitsuba Trading Co., Ltd.), coconard (registered trademark) (manufactured by Kao Corporation), ODO (manufactured by Nisshin Oillio Co., Ltd.), panacet (registered trademark) ) (Manufactured by Nippon Oil & Fats Co., Ltd.), TCG-M (manufactured by Higher Alcohol Industry Co., Ltd.), actor (manufactured by Riken Vitamin Co., Ltd.), and PALMESTER (manufactured by PALM-OLEO).

  These components (C) may be synthesized by a known method or may be used after obtaining commercially available products. (C) component can be used individually or in combination of 2 or more types.

  In the pharmaceutical composition of the present invention, the component (C) is preferably a clear liquid at 60 ° C.

  In the present invention, the content of component (C) is the type and amount of component (A) and component (B), the type and amount of other components, and the patient's condition (weight, age, sex, symptoms, physical condition, etc.) , And according to the dosage form of the pharmaceutical composition of the present invention. The content of the component (C) is not limited, but from the viewpoint of more prominently exerting the effects of the present invention, the total amount of the component (C) is preferably 15 to 99% by mass with respect to the total amount of the pharmaceutical composition, preferably Is 25 to 98% by mass, more preferably 30 to 97% by mass, still more preferably 40 to 96% by mass, and particularly preferably 50 to 95% by mass.

  Moreover, the compounding ratio of the component (A) and the component (C) in the pharmaceutical composition of the present invention can be appropriately set according to the type of the component (A), the type and amount of the other components, the use of the pharmaceutical composition, and the like. However, for example, with respect to 1 part by mass of component (A), the total amount of component (C) is 0.01 to 350 parts by mass, preferably 0.1 to 300 parts by mass, more preferably 0.5 to 250 mass parts, More preferably, it is 1-200 mass parts, More preferably, it is 2-150 mass parts, Most preferably, it can be 3-100 mass parts. When component (A) is fexofenadine or a salt thereof, for example, the total amount of component (C) is 0.1 to 70 parts by mass, preferably 0 with respect to 1 part by mass of fexofenadine or a salt thereof. 0.5 to 60 parts by mass, more preferably 1 to 50 parts by mass, still more preferably 1.5 to 40 parts by mass, and particularly preferably 2 to 30 parts by mass. When component (A) is epinastine or a salt thereof, for example, the total amount of component (C) is 1 to 120 parts by mass, preferably 2 to 100 parts by mass, preferably 1 part by mass of epinastine or a salt thereof. Is 3 to 90 parts by mass, more preferably 4 to 75 parts by mass, still more preferably 5 to 60 parts by mass, still more preferably 5 to 40 parts by mass, and particularly preferably 5 to 30 parts by mass. Can do. When component (A) is loratadine or a salt thereof, for example, the total amount of component (C) is 1 to 190 parts by weight, preferably 5 to 170 parts by weight, relative to 1 part by weight of loratadine or a salt thereof. The amount is preferably 10 to 150 parts by mass, more preferably 20 to 150 parts by mass, and particularly preferably 30 to 125 parts by mass. When the component (A) is olopatadine or a salt thereof, for example, the total amount of the component (C) is 1 to 200 parts by weight, preferably 3 to 175 parts by weight with respect to 1 part by weight of olopatadine or a salt thereof. Preferably, it is 5-150 mass parts, More preferably, it is 8-150 mass parts, Most preferably, it can be 10-125 mass parts. When the component (A) is emedastine or a salt thereof, for example, the total amount of the component (C) is 1 to 320 parts by mass, preferably 3 to 310 parts by mass with respect to 1 part by mass of emedastine or a salt thereof. Preferably, it is 5-310 mass parts, More preferably, it is 8-160 mass parts, More preferably, it is 10-150 mass parts, Most preferably, it can be 10-120 mass parts. When the component (A) is cetirizine, a salt thereof or an isomer thereof, for example, the total amount of the component (C) is 1 to 190 parts by weight, preferably 1 part by weight of the cetirizine, a salt thereof or an isomer thereof. 2 to 170 parts by mass, more preferably 3 to 150 parts by mass, still more preferably 5 to 125 parts by mass, still more preferably 5 to 65 parts by mass, and particularly preferably 10 to 62 parts by mass. it can. When the component (A) is a hot pepper extract, for example, the total amount of the component (C) is 0.1 to 75 parts by weight, preferably 0.5 to 60 parts by weight with respect to 1 part by weight of the hot pepper extract. More preferably, it is 0.5-50 mass parts, More preferably, it is 1-40 mass parts, More preferably, it is 1.5-30 mass parts, More preferably, it is 1.5-25 mass parts, Especially preferably, 2 to 30 parts by mass.

  Further, the blending ratio of the component (B) and the component (C) in the pharmaceutical composition of the present invention can be appropriately set according to the type of the component (B), the type and amount of the other component, the use of the pharmaceutical composition, and the like. However, from the viewpoint of exhibiting the effects of the present invention more remarkably, the total amount of the component (C) is 0.01 to 300 parts by mass, preferably 0.1%, with respect to 1 part by mass of the total amount of the component (B). -200 mass parts, More preferably, it is 0.5-100 mass parts, More preferably, it can be 3-25 mass parts.

[Bioactive ingredients]
In the present invention, the pharmaceutical composition may contain other components (bioactive components) as long as the effects of the present invention are sufficiently exerted.

As such a component, for example,
An antihistamine component (e.g., isothipentyl hydrochloride, iproheptin hydrochloride, dipheterol hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, triprolidine hydrochloride hydrate, tripelenamine hydrochloride, tondilamine hydrochloride, promethazine hydrochloride, methodirazine hydrochloride, Diphenhydramine salicylate, carbinoxamine diphenyldisulfonate, alimemazine tartrate, diphenhydramine tannate, diphenylpyraline theocrate, carbinoxamine maleate, chlorpheniramine maleate, promethazine methylene disalicylate)
Parasympathetic blockade components (eg, atropine, scopolamine, belladonna total alkaloids, belladonna extract, isopropamide iodide, datsura extract, funnel extract, etc.),
Sympathomimetic components (eg, methylephedrine, pseudoephedrine, phenylephrine, phenylpropanolamine, ephedrine, ethylephrine, methoxamine, middolin, methoxyphenamine or salts thereof),
Anti-inflammatory enzymes (for example, lysozyme, serrapeptase, bromelain, pronase, etc.), herbal medicine, and herbal medicine-derived components (for example, ginger, licorice, carrot, maoh, keihi, keigai, saishin, nantenjitsu, ohhi, beakshi, zenko, kokyo, Shazenshi, Gooh, Gadju, Sandalwood, Ginger, Gentiana, Fennel, Onji, Owaku, Auren, Chikusetsuninjin, Chimpi, Clove, Senegal, Shazenso, Shajin etc.),
Glycyrrhizic acids (for example, glycyrrhizic acid or a salt thereof),
Xanthine derivatives (for example, sodium caffeine benzoate, caffeine hydrate, caffeine such as anhydrous caffeine, theophylline, aminophylline, theobromine, diprofeline, proxyphylline, pentoxyphylline, etc.),
Antipyretic analgesic ingredients (for example, aspirin, aspirin aluminum, acetaminophen, etenzamide, sazapyrine, salicylamide, sodium salicylate, lactylphenetidine, ibuprofen, ketoprofen, thiaramide, aluminoprofen, loxoprofen, etc.)
Leukotriene antagonist (Montelukast, Pranlukast, Zafirlukast, etc.)
Antitussive ingredients (eg, achloramide, cloperastine, pentoxyberine (Carbetapentane), tipepidine, dibutate, dextromethorphan, codeine, dihydrocodeine, noscapine, etc.),
Expectorants (eg, potassium guaiacol sulfonate, guaifenesin, etc.), and mucosal protective components (eg, aluminum-based mucosal protective agents such as aminoacetic acid, dry aluminum hydroxide gel, dihydroxyaluminum aminoacetate; magnesium aluminate metasilicate, Aluminum silicate, hydrotalcite, magnesium hydroxide alumina, aluminum hydroxide gel, coprecipitation product of aluminum hydroxide / sodium bicarbonate, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / calcium carbonate / magnesium carbonate Coprecipitation products of magnesium, magnesium-based mucosal protective agents such as coprecipitation products of magnesium carbonate, magnesium oxide, magnesium hydroxide, magnesium silicate, magnesium hydroxide and potassium aluminum sulfate, etc. ), Etc.

  Among these, in the pharmaceutical composition of the present invention, at least one selected from the group consisting of belladonna total alkaloid, caffeine, glycyrrhizic acid, methylephedrine, pseudoephedrine, and salts thereof is preferable, and belladonna total alkaloid, caffeine, More preferred is at least one selected from the group consisting of glycyrrhizic acid and salts thereof. In this specification, the belladonna total alkaloid is a tropane-based alkaloid contained in the rhizome, root, or leaf of the herbal medicine belladonna (Atoropa belladonnna Linne), and is made using a suitable extractant such as ethanol, ether, water, etc. Yes, here we include both Belladonna alkaloids and Belladonna total alkaloids. The dose of belladonna total alkaloid is not particularly limited as long as it is within the range normally used in the art, but in the case of oral administration, the dose per day for an adult is usually 0.08 mg or more, preferably 0.10 mg. As mentioned above, it is particularly preferably 0.12 mg or more, and the upper limit is usually 0.8 mg or less, preferably 0.7 mg or less, particularly preferably 0.6 mg or less. Further, the dose of caffeine is not particularly limited as long as it is within the range normally used in the art, but in the case of oral administration, the dose per day for an adult is usually 20 mg or more, preferably 40 mg or more, particularly The upper limit is preferably 60 mg or more, and the upper limit is 400 mg or less, preferably 350 mg or less, particularly preferably 300 mg or less, taking into consideration the dose and pharmacological action. Further, the dose of glycyrrhizic acid or a salt thereof is not particularly limited as long as it is a range usually used in the art, but in the case of oral administration, the dose per day for an adult is usually 5 mg or more as glycyrrhizic acid, The upper limit is preferably 300 mg or less, more preferably 250 mg or less, and particularly preferably 200 mg or less in consideration of the dose and pharmacological action. The dosage is appropriately determined in consideration of the patient's condition (weight, age, symptoms, physical condition, etc.), and is not limited to the above.

  These components may be free forms or salts.

[Additive]
In this invention, as long as the effect of this invention is fully show | played, the pharmaceutical composition may contain the additive normally used for a soft capsule etc.

  Examples of such additives include surfactants other than the component (B), suspending agents (for example, gum arabic, gum arabic powder, xanthan gum, etc.), emulsifiers, stabilizers, buffers, solubilizers and oxidation agents. An inhibitor etc. can be mentioned. Although not limited, it is preferable to blend so as not to result in a composition that lowers the fluidity of the pharmaceutical composition so as to hinder the effects of the present invention. For example, polyvinylpyrrolidone is not preferable if it is added in an amount exceeding 6% because the fluidity of the pharmaceutical composition is lowered.

  In the present invention, the pharmaceutical composition may or may not contain water as long as the effects of the present invention are sufficiently exerted. The water content can be appropriately set according to the type and amount of other components, the use of the pharmaceutical composition, and the like. For example, the water content can be 20% by mass or less based on the total amount of the pharmaceutical composition. It is preferable to set it as mass% or less, It is more preferable to set it as 10 mass% or less, It is more preferable to set it as 8 mass% or less, It is more preferable to set it as 6 mass% or less, It is set as 4 mass% or less. More preferably, it is more preferably 2% by mass or less, and further preferably 1% by mass or less.

  In the present invention, the water used in the pharmaceutical composition may be physiologically or pharmaceutically acceptable. Examples of such water include distilled water, normal water, purified water, sterilized purified water, water for injection, and distilled water for injection. These definitions are based on the 16th revised Japanese Pharmacopoeia.

[Dosage form]
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. Among these solid preparations, from the viewpoint of more prominently exerting the effects of the present invention, the pharmaceutical composition of the present invention is a viewpoint in which components having an unpleasant taste and odor are effectively masked in the mouth and easy to take. Therefore, it is preferably used for a capsule and more preferably for a soft capsule.

  When the pharmaceutical composition of the present invention is used as a capsule, it can be prepared by filling the capsule film with the pharmaceutical composition of the present invention, and the filled pharmaceutical composition is preferably liquid. In this specification, liquid means having fluidity. Although not limited, it is sufficient that such fluidity is in a temperature range generated in a known production method when filling a capsule film or the like, and the fluidity is lost after filling the capsule film or the like. Also good. Moreover, although it is not limited, what is necessary is just to have fluidity | liquidity in body temperature from a viewpoint of dissolving a drug rapidly and releasing rapidly. Although not limited, for example, a gel that does not flow continuously and uniformly when filling a capsule film or the like is not preferable in terms of fluidity. In another embodiment, the pharmaceutical composition of the present invention can be for capsule film filling. In this specification, the capsule film refers to a film having a space inside and capable of holding contents such as an active ingredient in a confined state. The liquid property of the pharmaceutical composition to be filled is not particularly limited, but is preferably aqueous or oily, and more preferably oily.

  Although it does not specifically limit as a capsule membrane | film | coat which can be used in this invention, A soft capsule membrane | film | coat is preferable from a viewpoint which show | plays the liquid familiarity with respect to the capsule membrane | film | coat of pharmaceutical composition effectively. The base of the soft capsule film is not particularly limited, and starch, pullulan, cellulose, polyvinyl alcohol, gelatin, succinated gelatin and the like can be used, and starch, gelatin and succinylated gelatin are preferable, and gelatin and succinated gelatin are preferable. Is more preferable. You may use these individually or in combination of 2 or more types.

When gelatin is contained in the capsule film, the content of gelatin is not particularly limited, but is preferably 50 to 99.5% by mass and more preferably 60 to 99% by mass based on the total amount of the capsule film.

  The capsule film may contain a plasticizer, a gelling agent, a gelling aid, a colorant, a preservative, a fragrance, a pH adjuster, a surfactant, and the like within a range not impairing the effects of the present invention. Good. As the plasticizer, glycerin, mannitol, sorbitol, sucrose, fructose, propylene glycol, macrogol, polyvinylpyrrolidone, or the like can be used. Examples of gelling agents that can be used include gum arabic, alginic acid, carrageenan, agar, xanthan gum, guar gum, glucomannan, gellan gum, tamarind gum, far selelain, and pectin. As the gelation accelerator, ammonium chloride, potassium chloride, calcium chloride, sodium chloride, potassium citrate, sodium citrate, magnesium sulfate, potassium phosphate, calcium lactate and the like can be used. As the colorant, titanium oxide, tar pigment, caramel and the like can be used. As a preservative, methylparaben, ethylparaben, propylparaben, etc. can be used. As the fragrance, menthol or the like can be used. As the surfactant, polysorbate 80, polyoxyl 35 castor oil, or the like can be used. These may be used alone or in combination of two or more.

  The content ratio of the base constituting the soft capsule film is not limited as long as the effect of the present invention is exhibited. For example, 1 to 70 parts by mass of a plasticizer can be contained with respect to 100 parts by mass of the base. 5-60 mass parts is preferable, and 10-50 mass parts is more preferable.

  From the viewpoint of effectively achieving liquid familiarity with the capsule film of the pharmaceutical composition, the capsule film is preferably composed mainly of gelatin, more preferably containing gelatin and glycerin.

  The thickness of the soft capsule film is not limited as long as the effect of the present invention is achieved, but may be, for example, 0.001 to 2 mm, preferably 0.005 to 1.5 mm, 0.01 More preferably, it is -0.9 mm.

[Method for producing solid preparation]
In another embodiment of the present invention, (A) at least one selected from the group consisting of fexofenadine, epinastine, loratadine, olopatadine, emedastine, cetirizine, levocetirizine and salts thereof, and a spicy extract, and (B) It is possible to provide a method for producing a solid preparation characterized by coexisting at least one selected from the group consisting of a surfactant and a polyhydric alcohol and (C) a hydrophobic base. The type and amount of component (A), the type and amount of component (B), and the type and amount of component (C) are the same as those described in [Pharmaceutical composition] above. The type of solid preparation is the same as that described in the above [Dosage Form].

  The pharmaceutical composition of the present invention comprises, for example, a component (A), a component (B), a component (C), other components that are optionally added, and additives that are optionally added. Produced by mixing and stirring by method.

  The apparatus for mixing and stirring is not particularly limited, and for example, a high-speed stirrer such as a commercially available biomixer or homojetter or a high-speed pulverizer can be used.

  The pharmaceutical composition of the present invention is produced by filling a capsule film with a pharmaceutical composition containing the components (A), (B) and (C). The filling method is not particularly limited, and for example, a known method such as a rotary method or a seamless method can be employed. According to the present invention, since the pharmaceutical composition to be filled has more effective liquid familiarity with the capsule film, the filling process can be highly controlled. For example, in the case of the rotary method, in the process of discharging the pharmaceutical composition between two sheet-like capsule films, the liquid familiarity of the pharmaceutical composition is good. There is an effect that it hardly occurs. The present invention can also be suitably used when designing a capsule film to be thin, or when designing a microcapsule.

[Method of imparting an action of improving liquid familiarity to the capsule film]
The present invention also provides (A) at least one selected from the group consisting of fexofenadine, epinastine, loratadine, olopatadine, emedastine, cetirizine, levocetirizine and salts thereof, and a spicy extract, and (B) a surfactant and The present invention relates to a method for imparting a liquid conformity improving action to a capsule film to at least one selected from the group consisting of polyhydric alcohols and (C) a hydrophobic base in the pharmaceutical composition. . The type and amount of the component (A), the type and amount of the component (B), and the type and amount of the component (C) are the same as in the case of the above [pharmaceutical composition]. In this specification, the liquid familiarity with the capsule film refers to wetting at the contact surface between the capsule film and the content to be filled. As an index of liquid familiarity with the capsule film, for example, wetting of a droplet dropped on the capsule film can be represented by the size of the dynamic contact angle (advance angle). The larger the dynamic contact angle, the lower the wetting of the flowing liquid and the lower the familiarity with the liquid. The smaller the dynamic contact angle, the higher the wettability of the liquid flowing in contact with the capsule film, and the higher the liquid familiarity. When such “fluid familiarity with capsule film” is improved, it becomes possible to highly control the process of filling the capsule film with the contents. The effect of.

[Apply]
The pharmaceutical composition of the present invention can be used for the treatment of any disease for which the administration of component (A) is desired, such as bronchial asthma, allergic rhinitis, acute rhinitis, sinusitis, or these It can be used for various symptoms (such as nasal congestion, stuffy nose, heavy head, sneezing, sore throat, lax eyes). The pharmaceutical composition of the present invention can be used for internal use (for oral administration), for example.

  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 2 times a day. Therefore, the pharmaceutical composition of the present invention for a single administration preferably contains an amount obtained by dividing the above-mentioned daily dose by the number of administrations per day.

  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 Method 1: Method for Measuring Dynamic Contact Angle (Advance Angle)]
Using a contact angle meter DM-501 (manufactured by Kyowa Interface Science Co., Ltd.), according to the measurement procedure of the extension method of the contact angle meter, the dynamic contact angles of the liquid compositions of Test Examples 1-1 to 1-4 described later (Advance angle) was measured.

  Specifically, the capsule film was placed on the contact angle meter stage so that the seamless surface faced upward. The test solution was set in the contact angle meter dispenser. A drop of 1 μL of the test solution was dropped on the capsule film at room temperature to form a hemisphere. Next, immediately, the tip of the liquid discharge part of the dispenser was allowed to land on the upper center of the hemisphere of the test liquid. In this state, the test liquid was continuously discharged at a discharge speed of 6 μL / second, and the shape of the droplet was photographed 20 times from the side surface every 0.1 second. In order to match the measurement conditions, the test solutions to be paired when calculating the liquid familiarity improvement rate were continuously measured under the same temperature conditions. Unless otherwise specified, the measurement was performed at room temperature.

  Next, the photographed image was analyzed using analysis software FAMAS of the same contact angle meter, and the contact angle was obtained for each image. Here, the contact angle is the angle between the tangent line drawn on the surface of the capsule film, the contact point P between the test liquid and air, and the tangent line drawn on the surface of the capsule film on the side containing the test liquid. Means. There are two contact points P on the left and right of each droplet. The contact angle changed due to the ejection of the test liquid, and the change in the contact angle became smaller as the droplet expanded. Therefore, when the average value of the left and right contact angles of the droplet is calculated for each image, the average values are arranged in the order in which the images were taken, and five consecutive contact angles are selected, the standard deviation of the five average values The first average value when the angle first becomes less than 2.5 ° (the average value of the left and right contact angles in the first image taken out of the five average values) is the dynamic contact angle measurement in the same measurement. Value. For all the test solutions, no standard deviation of 2.5 ° or more was observed after the standard deviation first became less than 2.5 °. Even when the contact angle did not change during the process of expanding the droplet, the measured value of the dynamic contact angle was obtained according to the above criteria.

  The above operation was repeated three times for each test solution, and the average value of the three measured values obtained was taken as the dynamic contact angle of the test solution. The standard deviation of the three measurements was 2.0 ° or less for all test solutions.

[Test Method 2: Method for Measuring Dynamic Contact Angle (Advance Angle)]
The dynamic contact angle of each liquid composition of Test Examples 1-5 to 6-2 to be described later was measured. The dynamic contact angle measurement method calculates the average value of the left and right contact angles for each image, and selects five consecutive values by arranging the average values in the order in which the images were photographed. The first average value when the standard deviation first becomes 2.0 ° or less (the average value of the left and right contact angles in the image taken first among the five average values) is the dynamic contact angle in the same measurement. The procedure shown in the above test method 1 was followed except that the measured value was set to. For all the test solutions, no standard deviation greater than 2.0 ° was observed after the standard deviation first became 2.0 ° or less.

[Test Example 1-1] Evaluation 1 of dynamic contact angle (advance angle)
Each liquid composition shown in Table 1 was prepared by a conventional method and used as a test solution. Panacet 810 (NOF Corporation) was used as the medium chain fatty acid triglyceride. Polysorbate 80, TO-10MV (Nikko Chemicals Co., Ltd.) (HLB15.0) was used. As the capsule film, a gelatin film containing gelatin, glycerin and titanium oxide (product name: Roth Algard rhinitis soft capsule EX, manufactured by Rohto Pharmaceutical Co., Ltd.) was used. The dynamic contact angle was measured immediately after preparing each test solution according to the procedure shown in Test Method 1 (average of three measured values). From the following [Formula 1], the liquid familiar improvement rate of each test solution with respect to Comparative Example 1 was calculated. The calculated results are also shown in Table 1.
[Formula 1]
Solution familiarity ratio (%) with respect to Comparative Example 1 = {1- (Dynamic contact angle of each test solution / Dynamic contact angle of Comparative Example 1)} × 100

  As shown in Table 1, when (A) component was combined with (C) component, it discovered that there was a new subject that liquid familiarity will deteriorate (comparative example 3). Furthermore, also when combining (C) component and (B) component, it became a result which worsens liquid familiarity (comparative example 2).

  On the other hand, surprisingly, when the (A) component, the (B) component, and the (C) component are combined, the dynamic contact angle is decreased, that is, the liquid familiarity to the capsule film is improved. It was confirmed (Examples 1 and 2).

[Test Example 1-2] Evaluation 2 of dynamic contact angle (advance angle)
The dynamic contact angle (advance angle) was determined in the same manner as in Test Example 1-1. Using the liquid composition shown in Table 2, the capsule film is gelatin film containing gelatin, glycerin, titanium oxide, D-sorbitol, ethyl paraben, propyl paraben, titanium oxide and Yellow No. 5 (product name: Sepie (registered trademark)) ) Gastritis soft N, manufactured by Zeria Shinyaku Co.) was used. As the medium chain fatty acid triglyceride, Panacet 810 (manufactured by NOF Corporation) was used (hereinafter the same). As polysorbate 80, TO-10MV (manufactured by Nikko Chemicals Co., Ltd.) (HLB15.0) was used (the same applies hereinafter). Subsequently, the comparative example 1 of [Formula 1] was made into the comparative example 4, and the liquid familiar improvement rate of each test liquid with respect to the comparative example 4 was computed. The calculated results are also shown in Table 2.

  As shown in Table 2, when the (A) component, the (B) component, and the (C) component are combined, the dynamic contact angle is reduced, that is, it is confirmed that the liquid familiarity to the capsule film is improved. (Example 3).

[Test Example 1-3] Evaluation 3 of dynamic contact angle (advance angle)
The dynamic contact angle was determined by the same method as in Test Example 1-1. Using the liquid composition shown in Table 3, a gelatin film containing succinated gelatin and glycerin (product name: Omninin Rhinitis Capsule S, manufactured by All Yakuhin Kogyo Co., Ltd.) was used as the capsule film. Subsequently, the comparative example 1 of [Formula 1] was set as the comparative example 7, and the liquid familiarity improvement rate of each test liquid with respect to the comparative example 7 was calculated. The calculated results are also shown in Table 3.

  As shown in Table 3, when the (A) component, the (B) component, and the (C) component are combined, the dynamic contact angle is reduced, that is, it is confirmed that the liquid familiarity to the capsule film is improved. (Example 4).

[Test Example 1-4] Evaluation 4 of dynamic contact angle (advance angle)
The dynamic contact angle was determined by the same method as in Test Example 1-1. According to the formulation described in Table 4, each liquid composition was prepared. The same composition as in Test Example 1-1 was used for the capsule film. As the glycerin fatty acid ester, Poem S-100 (Riken Vitamin Co., Ltd.) was used (the same applies hereinafter). As soybean oil, soybean oil YM (Nisshin Oillio Group Co., Ltd.) was used (hereinafter the same). Subsequently, the comparative example 1 of [Formula 1] was set as the comparative example 10, and the liquid familiar improvement rate of each test liquid with respect to the comparative example 10 was calculated. The calculated results are also shown in Table 4.

  As shown in Table 4, when a surfactant and a hydrophobic base different from those of Test Examples 1-1 to 1-3 are used, the component (C) is combined with the component (A) or the component (B). The composition produced a problem that the dynamic contact angle increased, that is, the liquid familiarity deteriorated (Comparative Examples 11 and 12).

  On the other hand, when the (A) component, the (B) component, and the (C) component were combined, the dynamic contact angle decreased, that is, it was confirmed that the liquid familiarity to the capsule film was improved (Example) 5).

[Test Example 1-5] Evaluation 5 of dynamic contact angle (advance angle)
The dynamic contact angle (advance angle) was measured immediately after preparing each test solution according to the procedure shown in Test Method 2 above (average of three measured values). Using the liquid composition shown in Table 5, the capsule film used was a gelatin film containing gelatin, glycerin, titanium oxide, paraben, and polysorbate 80 (product name: Korgen Kowa rhinitis soft mini capsule, manufactured by Kowa Co., Ltd.). . Among the components (A), a spicy extract was used that satisfies the Shinyi items listed in the 17th revised Japanese Pharmacopoeia (the same applies hereinafter). Among the components (B), PMS-1CV (manufactured by Nikko Chemicals Co., Ltd.) was used as the propylene glycol fatty acid ester (the same applies hereinafter). As the polyoxyethylene hydrogenated castor oil, HCO-60 (manufactured by Nikko Chemicals Co., Ltd.) was used (the same applies hereinafter). As sorbitan fatty acid ester, SO-15V (manufactured by Nikko Chemicals Co., Ltd.) was used (the same applies hereinafter). Next, assuming that Comparative Example 1 of [Formula 1] was Comparative Example A-1, the liquid familiarity improvement rate of each test solution with respect to Comparative Example A-1 was calculated. In Example A-4, Comparative Example A-3, and Comparative Example A-1 corresponding thereto, each test solution was measured at 40 ° C. The value measured at room temperature was used for Comparative Example A-1 in the case of calculating other Examples and Comparative Examples other than Example A-4 and Comparative Example A-3. The calculated results are also shown in Table 5.

  As shown in Table 5, when the component (C) and the component (B) were contained in various combinations, it was found that there was a new problem that the liquid familiarity deteriorated (Comparative Example A). -2 to A-5).

  On the other hand, when the (A) component, the (B) component, and the (C) component were combined, the dynamic contact angle decreased, that is, it was confirmed that the liquid familiarity to the capsule film was improved (Example) A-1 to A-9). In addition to the components (A) to (C), it was confirmed that the liquid compatibility with the capsule film was further improved by further adding belladonna total alkaloid, anhydrous caffeine or dipotassium glycyrrhizinate (Example A). -2, A-6, A-7).

[Test Example 1-6] Evaluation of dynamic contact angle (advance angle) 6
The dynamic contact angle (advance angle) was determined in the same manner as in Test Example 1-5. Using the liquid compositions shown in Table 6, for Examples A-10 to A-11 and Comparative Examples A-6 to A-9, the capsule film was the same composition as in Test Example 1-5 (Korgen Kowa Rhinitis Soft Mini capsules) were used. For Examples A-12 to A-13 and Comparative Examples A-10 to A-12, the same composition (Roth Algard rhinitis soft capsule EX) as in Test Example 1-1 was used as the capsule film. Among the components (B), Surf Hope SE PHARMA J-1805 (manufactured by Mitsubishi Chemical Foods) (HLB5) was used as the sucrose fatty acid ester (the same applies hereinafter). As the soybean lecithin, lecinol S-10M (manufactured by Nikko Chemicals Co., Ltd.) was used (the same applies hereinafter). Then, for Example A-10 and Comparative Example A-7, the Comparative Example 1 of [Formula 1] was set as Comparative Example A-6, and the liquid familiarity improvement rate of each test solution with respect to Comparative Example A-6 was calculated. For Example A-11 and Comparative Example A-9, Comparative Example 1 of [Formula 1] was set as Comparative Example A-8, and the liquid familiarity improvement rate of each test solution with respect to Comparative Example A-8 was calculated. Regarding Examples A-12 to A-13 and Comparative Examples A-11 to A-12, Comparative Example 1 of [Formula 1] is referred to as Comparative Example A-10, and the liquid familiarity of each test solution with respect to Comparative Example A-10 The improvement rate was calculated. In Example A-10, Comparative Example A-6, and Comparative Example A-7, each test solution was measured at 40 ° C. The calculated results are also shown in Table 6.

  As shown in Table 6, it was found that there is a new problem that the liquid familiarity deteriorates even when the component (C) and the component (B) are contained in various combinations (Comparative Example A). -7, A-9, A-11, A-12).

  On the other hand, when the (A) component, the (B) component, and the (C) component were combined, the dynamic contact angle decreased, that is, it was confirmed that the liquid familiarity to the capsule film was improved (Example) A-10 to A-13).

[Test Example 2-1] Evaluation of dynamic contact angle (advance angle) 7
The dynamic contact angle (advance angle) was determined in the same manner as in Test Example 1-5. The liquid composition shown in Table 7 was used, and the same capsule composition as in Test Example 1-1 (Algard rhinitis soft capsule EX) was used as the capsule film. Next, for Examples 2-1 to 2-3 and Comparative Examples 2-2 to 2-4, Comparative Example 1 of [Formula 1] is referred to as Comparative Example 2-1, and each of the test solutions for Comparative Example 2-1 is used. The liquid familiarity improvement rate was calculated. For Example 2-4 and Comparative Example 2-6, Comparative Example 1 of [Formula 1] was set as Comparative Example 2-5, and the liquid familiarity improvement rate of each test solution with respect to Comparative Example 2-5 was calculated. About Example 2-5 and Comparative Example 2-8, the Comparative Example 1 of [Formula 1] was set as Comparative Example 2-7, and the liquid familiarity improvement rate of each test solution with respect to Comparative Example 2-7 was calculated. The calculated results are also shown in Table 7.

  As shown in Table 7, even when cetirizine hydrochloride, which is a component (A) different from Test Examples 1-1 to 1-6, was used, the composition in which the component (A) was combined with the component (C), The dynamic contact angle increased, that is, the problem that the liquid familiarity deteriorated (Comparative Example 2-3). Moreover, also when (C) component and (B) component were contained in various combinations, it became a result which worsened liquid familiarity (Comparative Examples 2-2, 2-4, 2-6, 2- 8).

  On the other hand, when the (A) component, the (B) component, and the (C) component were combined, the dynamic contact angle decreased, that is, it was confirmed that the liquid familiarity to the capsule film was improved (Example) 2-1 to 2-5). It was confirmed that by adding anhydrous caffeine in addition to the components (A) to (C), the liquid familiarity to the capsule film was further improved (Example 2-2).

[Test Example 3-1] Evaluation of dynamic contact angle (advance angle) 8
The dynamic contact angle (advance angle) was determined in the same manner as in Test Example 1-5. Using the liquid composition shown in Table 8, the capsule film was gelatin film containing gelatin, D-sorbitol, povidone, macrogol, glycerin, blue No. 1 (Product name: Estack rhinitis soft varnish cap, manufactured by SS Pharmaceutical Co., Ltd.) ) Was used. Subsequently, the comparative example 1 of [Formula 1] was set as the comparative example 3-1, and the liquid familiarity improvement rate of each test solution with respect to the comparative example 3-1 was calculated. The calculated results are also shown in Table 8.

  As shown in Table 8, when epinastine hydrochloride, which is a component (A) different from Test Examples 1-1 to 1-6, was used, the composition in which the component (A) was combined with the component (C) The dynamic contact angle increased, that is, the problem that the liquid familiarity deteriorated (Comparative Example 3-2).

  On the other hand, when the (A) component, the (B) component, and the (C) component were combined, the dynamic contact angle decreased, that is, it was confirmed that the liquid familiarity to the capsule film was improved (Example) 3-1 to 3-4).

[Test Example 3-2] Evaluation of dynamic contact angle (advance angle) 9
The dynamic contact angle (advance angle) was determined in the same manner as in Test Example 1-5. The liquid composition shown in Table 9 was used, and the capsule film used was a gelatin film (product name: Daytona S, manufactured by All Yakuhin Kogyo Co., Ltd.) containing succinated gelatin, concentrated glycerin, titanium oxide and yellow ferric oxide. . Subsequently, the comparative example 1 of [Formula 1] was made into Comparative Example 3-3, and the liquid familiar improvement rate of each test liquid with respect to Comparative Example 3-3 was calculated. The calculated results are also shown in Table 9.

  As shown in Table 9, when the component (C) and the component (B) were contained in various combinations, it was found that there was a new problem that the liquid familiarity deteriorated (Comparative Example 3). -4 to 3-7).

  On the other hand, when the (A) component, the (B) component, and the (C) component were combined, the dynamic contact angle decreased, that is, it was confirmed that the liquid familiarity to the capsule film was improved (Example) 3-5 to 3-8).

[Test Example 3-3] Evaluation of dynamic contact angle (advance angle) 10
The dynamic contact angle (advance angle) was determined in the same manner as in Test Example 1-5. The liquid composition shown in Table 10 was used, and the same capsule composition as in Test Example 1-1 (Algard rhinitis soft capsule EX) was used as the capsule film. Next, for Examples 3-9 to 3-12 and Comparative Example 3-9, Comparative Example 1 of [Formula 1] was set as Comparative Example 3-8, and the familiarity improvement rate of each test solution with respect to Comparative Example 3-8 Was calculated. For Examples 3-13 to 3-14 and Comparative Example 3-11, the Comparative Example 1 of [Formula 1] was set as Comparative Example 3-10, and the liquid familiarity improvement rate of each test solution with respect to Comparative Example 3-10 was calculated. did. About Example 3-15 and Comparative Example 3-13, the Comparative Example 1 of [Formula 1] was set as Comparative Example 3-12, and the liquid familiarity improvement rate of each test solution with respect to Comparative Example 3-12 was calculated. The calculated results are also shown in Table 10.

  As shown in Table 10, it was found that there is a new problem that the liquid familiarity deteriorates even when the component (C) and the component (B) are contained in various combinations (Comparative Example 3). -9, 3-11, 3-13).

  On the other hand, when the (A) component, the (B) component, and the (C) component were combined, the dynamic contact angle decreased, that is, it was confirmed that the liquid familiarity to the capsule film was improved (Example) 3-9 to 3-15). In addition to the components (A) to (C), it was confirmed that the liquid familiarity to the capsule film was further improved by further adding belladonna total alkaloid, anhydrous caffeine or dipotassium glycyrrhizinate (Example 3). -10 to 3-12).

[Test Example 4-1] Evaluation of dynamic contact angle (advance angle) 11
The dynamic contact angle (advance angle) was determined in the same manner as in Test Example 1-5. Using the liquid composition shown in Table 11, for Examples 4-1 to 4-5 and Comparative Examples 4-1 to 4-5, the capsule film was the same composition as in Test Example 1-1 (Roth Algard rhinitis soft capsule) EX) was used. About Example 4-6 and Comparative Examples 4-6 to 4-7, the same composition (Daytona S) as the test example 3-2 was used for the capsule film. Next, for Examples 4-1 to 4-3 and Comparative Examples 4-2 to 4-3, Comparative Example 1 of [Formula 1] is referred to as Comparative Example 4-1, and each of the test solutions for Comparative Example 4-1 is used. The liquid familiarity improvement rate was calculated. For Examples 4-4 to 4-5 and Comparative Example 4-5, assuming that Comparative Example 1 of [Formula 1] is Comparative Example 4-4, the liquid familiarity improvement rate of each test solution with respect to Comparative Example 4-4 was calculated. did. For Example 4-6 and Comparative Example 4-7, Comparative Example 1 of [Formula 1] was set as Comparative Example 4-6, and the liquid familiarity improvement rate of each test solution with respect to Comparative Example 4-6 was calculated. In Example 4-4, Example 4-5, Comparative Example 4-4, and Comparative Example 4-5, each test solution was measured at 40 ° C. The calculated results are also shown in Table 11.

  As shown in Table 11, when loratadine, which is a component (A) different from Test Examples 1-1 to 1-6, was used, the composition in which the component (A) was combined with the component (C) was dynamic. The problem that the contact angle increased, that is, the liquid familiarity deteriorated (Comparative Example 4-3) was caused. Moreover, also when (C) component and (B) component were contained in various combinations, it became a result which worsened liquid familiarity (Comparative Examples 4-2, 4-5, 4-7).

  On the other hand, when the (A) component, the (B) component, and the (C) component were combined, the dynamic contact angle decreased, that is, it was confirmed that the liquid familiarity to the capsule film was improved (Example) 4-1 to 4-6).

[Test Example 5-1] Evaluation of dynamic contact angle (advance angle) 12
The dynamic contact angle (advance angle) was determined in the same manner as in Test Example 1-5. The liquid composition shown in Table 12 was used, and the same capsule composition as in Test Example 3-1 (Estach rhinitis soft varnish cap) was used as the capsule film. Next, assuming that Comparative Example 1 of [Formula 1] was Comparative Example 5-1, the liquid familiarity improvement rate of each test solution with respect to Comparative Example 5-1 was calculated. The calculated results are also shown in Table 12.

  As shown in Table 12, when olopatadine hydrochloride or emedastine fumarate, which is component (A) different from Test Examples 1-1 to 1-6, was used, component (A) The composition which combined these produced a problem that the dynamic contact angle increased, that is, the liquid familiarity deteriorated (Comparative Examples 5-3 and 5-4).

  On the other hand, when the (A) component, the (B) component, and the (C) component were combined, the dynamic contact angle decreased, that is, it was confirmed that the liquid familiarity to the capsule film was improved (Example) 5-1 to 5-3).

[Test Example 6-1] Evaluation of dynamic contact angle (advance angle) 13
The dynamic contact angle (advance angle) was determined in the same manner as in Test Example 1-5. Using the liquid composition shown in Table 13, for Examples 6-1 to 6-3 and Comparative Examples 6-1 to 6-5, the capsule film was the same composition as in Test Example 3-1. Cap). For Examples 6-4 to 6-6 and Comparative Examples 6-6 to 6-7, the same composition (Algard rhinitis soft capsule EX) as in Test Example 1-1 was used as the capsule film. Next, with respect to Examples 6-1 to 6-3 and Comparative Examples 6-2 to 6-5, Comparative Example 1 of [Formula 1] is referred to as Comparative Example 6-1, and each of the test solutions for Comparative Example 6-1 is used. The liquid familiarity improvement rate was calculated. For Examples 6-4 to 6-6 and Comparative Example 6-7, assuming that Comparative Example 1 of [Formula 1] is Comparative Example 6-6, the liquid familiarity improvement rate of each test solution with respect to Comparative Example 6-6 was calculated. did. The calculated results are also shown in Table 13.

  As shown in Table 13, even when a spice extract is used as the component (A), the composition obtained by combining the component (A) with the component (C) has an increased dynamic contact angle, that is, liquid familiarity. A problem of worsening occurred (Comparative Example 6-3).

  On the other hand, when the (A) component, the (B) component, and the (C) component were combined, the dynamic contact angle decreased, that is, it was confirmed that the liquid familiarity to the capsule film was improved (Example) 6-1 to 6-6). In addition to the components (A) to (C), the addition of belladonna total alkaloid or dipotassium glycyrrhizinate was confirmed to further improve the liquid familiarity to the capsule film (Examples 6-5 to 6). -6).

[Test Example 6-2] Evaluation of dynamic contact angle (advance angle) 14
The dynamic contact angle (advance angle) was determined in the same manner as in Test Example 1-5. Using the liquid composition shown in Table 14, for Examples 6-7 to 6-9 and Comparative Examples 6-8 to 6-13, the capsule film had the same composition (Daytona S) as Test Example 3-2. Using. For Examples 6-10 to 6-11 and Comparative Examples 6-14 to 6-15, the same composition (Algard rhinitis soft capsule EX) as in Test Example 1-1 was used as the capsule film. Next, for Example 6-7 and Comparative Example 6-9, Comparative Example 1 of [Formula 1] was set as Comparative Example 6-8, and the liquid familiarity improvement rate of each test solution with respect to Comparative Example 6-8 was calculated. For Example 6-8 and Comparative Example 6-11, Comparative Example 1 of [Formula 1] was set as Comparative Example 6-10, and the familiarity improvement rate of each test solution with respect to Comparative Example 6-10 was calculated. About Example 6-9 and Comparative Example 6-13, the Comparative Example 1 of [Formula 1] was set as Comparative Example 6-12, and the familiarity improvement rate of each test solution with respect to Comparative Example 6-12 was calculated. For Examples 6-10 to 6-11 and Comparative Example 6-15, assuming that Comparative Example 1 of [Formula 1] is Comparative Example 6-14, the liquid familiarity improvement rate of each test solution with respect to Comparative Example 6-14 was calculated. did. The calculated results are also shown in Table 14.

  As shown in Table 14, when the component (C) and the component (B) were contained in various combinations, it was found that there was a new problem that the liquid familiarity deteriorated (Comparative Example 6). -9, 6-11, 6-13, 6-15).

  On the other hand, when the (A) component, the (B) component, and the (C) component were combined, the dynamic contact angle decreased, that is, it was confirmed that the liquid familiarity to the capsule film was improved (Example) 6-7 to 6-11). It was confirmed that the liquid familiarity to the capsule film was further improved by further containing anhydrous caffeine in addition to the components (A) to (C) (Example 6-11).

  In the composition which combined the above-mentioned (A) component, (B) component, and (C) component, the dynamic contact angle fell and the liquid familiarity with respect to the capsule film | membrane improved. That is. In the composition of this invention, since it becomes a capsule with the high uniformity of quality and the effect | action of (A) component being exhibited effectively, the rhinitis improvement effect is recognized more notably.

[Test Example 7-1] Drug release test Each liquid composition was prepared according to the formulation shown in Table 15. 7 mL of purified water was added to the test tube, and 0.7 g of each of Comparative Examples 7-1, 7-2 and Example 7-1 was added dropwise, and the mixture was shaken and stirred 10 times up and down. Immediately visually observed and allowed to stand for 3 minutes, turbidity was measured with a turbidimeter 2100AN (manufactured by HACK).

  The results are shown in Table 15 and FIG. In Comparative Example 7-1, the liquid composition precipitated and did not mix with water at all. In Comparative Example 7-2, the liquid composition adhered to the test tube and hardly mixed with water. In contrast, Example 7-1 was mixed with water and uniformly dispersed. As for turbidity, Example 7-1 showed a remarkably high value compared with Comparative Example 7-1 and Comparative Example 7-2, and it has confirmed that dispersibility was high. Therefore, Example 7-1 was found to be a composition that is easily dispersed in water (fast dissolution effect), excellent in drug release in the body (fast release effect), and easily absorbed in the body. .

[Production Examples 1 to 40]
Using a well-known technique, a liquid composition is prepared about the formulation example described in Tables 16-19, and a soft capsule is manufactured. The mass in the table was the daily dose.

Claims (6)

(A) at least one selected from the group consisting of fexofenadine, epinastine, loratadine, olopatadine, emedastine, cetirizine, levocetirizine and salts thereof, and a hot pepper extract;
(B) at least one selected from the group consisting of a surfactant and a polyhydric alcohol;
(C) A pharmaceutical composition containing a hydrophobic base.   The pharmaceutical composition according to claim 1, wherein the hydrophobic base (C) is an oil or fat, a wax or a fat-soluble vitamin.   The pharmaceutical composition according to claim 1 or 2, which is a liquid pharmaceutical composition.   The capsule with which the pharmaceutical composition of Claims 1-3 is filled in the capsule membrane | film | coat.   The pharmaceutical composition according to claims 1 to 3, which is fast-dissolving and / or fast-releasing. (A) at least one selected from the group consisting of fexofenadine, epinastine, loratadine, olopatadine, emedastine, cetirizine, levocetirizine and salts thereof, and a hot pepper extract;
(B) at least one selected from the group consisting of a surfactant and a polyhydric alcohol;
(C) A method for imparting to the pharmaceutical composition an effect of improving liquid conformity to the capsule film, comprising coexisting a hydrophobic base with the pharmaceutical composition.

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