JP2003012514A - Pharmaceutical composition - Google Patents

Abstract

(57) [Problem] To provide a pharmaceutical composition having an enhanced effect on sputum symptoms caused by a cold or the like. (A) one or more of salts selected from (a) epradinone, oxerazine and salts thereof; and (b) isothipendyl, diphenylpyramine, diphenhydramine, dipheterol, triprolidine, tripelenamine, tondylamine, phenetazine, methdilazine, carbinoxamine, alimemazine, A pharmaceutical composition comprising at least one selected from mebuhydroline, promethazine, chlorpheniramine, iproheptin and salts thereof.

Description

Description: TECHNICAL FIELD [0001] The present invention relates to a pharmaceutical composition characterized by eliminating or reducing sputum symptoms. 2. Description of the Related Art The treatment of colds is mainly symptomatic treatments aimed at improving individual cold symptoms. In particular, cough symptoms that mainly appear in the late to late stage of the cold sickness are a lot of energy consumption because of rapid exercise of many parts of the chest,
It is thought to cause a prolongation of the overall cold symptoms based on a decrease in physical strength and resistance. [0003] In order to suppress such cough symptoms, it is generally known to use a central antitussive such as codeines which act on the cough center to suppress coughing and suppress coughing by suppressing reflex excitement of the cough center. ing. [0004] Eprazinone and oxerazine are used as antitussives. Isotipendyl, diphenylpyrazine, diphenhydramine, dipheterol, triprolidine, tripelenamine, tondylamine, phenetazine, methdilazine, carbinoxamine, alimemazine,
Mebuhydroline, promethazine, chlorpheniramine,
Iproheptin has been used as an antihistamine and has been shown to suppress cough caused by atopic constitution. [0005] However, the direct removal or reduction effect on sputum symptoms when these components are combined at the same time has not been known so far. [0006] The object of the present invention is to provide viral cold, bacterial cold, influenza, tonsillitis,
It is an object of the present invention to provide a pharmaceutical composition having an excellent effect in removing or reducing sputum symptoms that accompany an allergy, hay fever, atopy, etc. Means for Solving the Problems As a result of intensive studies for the above purpose, the inventors of the present invention have found that certain antitussives eprazinone and oxerazine are added as active ingredients to isohistendyl, diphenylpyraline, diphenhydramine as antihistamines. , Dipheterol, triprolidine, tripelenamine, tondylamine, phenetazine, methdilazine,
By combining carbinoxamine, alimemazine, mebuhydroline, promethazine, chlorpheniramine, iproheptin or a salt thereof, it has been found that the present invention has a dramatic effect on the removal and alleviation of cough symptoms caused by various causes. It was completed. That is, the present invention relates to (a) epradinone,
One or more selected from oxerazine and salts thereof, and (b) isotipendyl, diphenylpyrazine, diphenhydramine, dipheterol, triprolidine, tripelenamine, tondiamine, phenetazine, methdilazine, carbinoxamine, alimedine, mebuhydroline, promethazine, chlorpheniramine, and iproheptin. A pharmaceutical composition comprising one or more selected from these salts. The compounding amount of the pharmaceutical composition of the present invention is as follows.
5 to 100 mg is preferred, and 30 to 90 mg is particularly preferred. Oxerazine and its salt are preferably 10 to 80 mg, and 20 to 6 mg.
0 mg is particularly preferred. The amount of isotipendyl and a salt thereof is preferably 2 to 15 mg, and particularly preferably 3.5 to 12 mg.
The amount of diphenylpyraline and its salt is preferably 1 to 10 mg, and 2
-9 mg is particularly preferable, diphenhydramine and its salt are preferably 20-200 mg, and 37.5-150 mg is particularly preferable, and dipheterol and its salt are 22.5-120.
mg is preferred, 45 to 90 mg is particularly preferred, triprolidine and a salt thereof are preferably 1 to 10 mg, particularly preferably 2 to 6 mg, and tripelenamine or a salt thereof is preferably 20 to 120 mg, particularly preferably 37.5 to 100 mg. 12.5 to 80 mg of tondylamine and its salt are preferred, and 25 to 60 mg.
mg is particularly preferred, and phenetazine and its salt are 12.5 mg.
150-150 mg is preferred, 25-135 mg is particularly preferred, methdilazine and its salt are preferably 2-10 mg, and 4-8 mg is particularly preferred, and carbinoxamine and its salt are 1.5-1.5 mg.
16 mg is preferred, and 3.5 to 12 mg is particularly preferred, and alimemazine and its salt is preferably 1 to 10 mg, and 2.5 to 7.5.
mg is particularly preferred, and mebuhydroline and its salts are 37.
5-200 mg is preferred, 75-150 mg is particularly preferred,
Promethazine and its salt are preferably 5 to 50 mg, and 7.5 to
40 mg is particularly preferred, and chlorpheniramine and a salt thereof are preferably 1 to 16 mg, particularly preferably 1.5 to 12 mg,
The amount of iproheptin and a salt thereof is preferably 37.5 to 200 mg, and particularly preferably 75 to 150 mg. [0010] (a) Eprazinone, oxerazine and their salts are compounded in the following amounts: (b) isotipendil, diphenylpyramine, diphenhydramine, dipheterol, triprolidine, tripelenamine, tondylamine, phenetazine, methdilazine, carbinoxamine, alimedazine, mebuhydrolin, promethazine, chlorazine. It is usually 0.05 part by weight or more, preferably 0.1 to 6 parts by weight, per part by weight of pheniramine, iproheptin and salts thereof.
0 parts by weight. In the present invention, the salt means a pharmaceutically acceptable salt, for example, hydrochloride, nitrate, sulfate, sulfonate, diphenyldisulfonate, phosphate, oxalate, maleic acid Inorganic or organic acid salts such as salts, fumarate, citrate, salicylate, methylene disalicylate, tartrate, tannate, teocrate, hydrobromide and the like can be mentioned. BEST MODE FOR CARRYING OUT THE INVENTION The pharmaceutical composition of the present invention can be usually orally administered to an adult once or several times a day. This dose can be appropriately increased or decreased depending on the age, weight, and medical condition. [0013] The pharmaceutical composition of the present invention comprises a tablet,
It is used as a formulation for oral administration forms such as capsules, granules, fine granules, powders, chewables, foaming agents, drops, dissolving agents in the mouth, dry syrups, and oral liquids. These preparations can be prepared by a conventional method. In the case of solid preparations, the carriers used for the preparation of preparations include excipients such as lactose, starch, sugar, mannitol and crystalline cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, gelatin and polyvinylpyrrolidone (PVP). There are binders, disintegrators such as carboxymethylcellulose calcium and low-substituted hydroxypropylcellulose, and lubricants such as magnesium stearate, hydrogenated castor oil, and talc. In addition, if necessary, dissolution aids, buffers, and preservatives ,
Flavors, pigments, flavoring agents and the like can be used. [0015] In the oral liquid preparation, the carrier used for the preparation of the preparation includes surface active agents such as sucrose fatty acid esters, polyoxyl stearate, polyoxyethylene polyoxypropylene glycols and polyoxyethylene mono fatty acid esters. Agents, thickeners such as synthetic aluminum silicate, magnesium silicate, magnesium carbonate, magnesium oxide, and magnesium aluminate metasilicate; organic acid and inorganic acid pH adjusters such as citrate buffer and phosphate buffer In addition, if necessary, a solubilizing agent, a buffer, a preservative, a flavor, a pigment, a sweetener, and the like can be used. The pharmaceutical composition of the present invention may optionally contain other drugs in addition to the above-mentioned components, if necessary. Also,
These components can be used alone or as a mixture of each other. Usually, cold drug standards, antitussive expectorant standards, etc. listed in the Pharmaceutical Manufacturing Guidelines (2000 edition, supervised by the Pharmaceutical Affairs Committee, published by Jiho Co., Ltd.) It is blended according to. The present invention will be described in more detail with reference to the following examples and test examples, but the present invention is not limited to the following examples. Example 1 After weighing and thoroughly mixing the following components, the mixed powder was tableted with a tableting machine (Collect 19, manufactured by Kikusui Seisakusho) to obtain a tablet weighing 200 mg per tablet. Epradinone hydrochloride 60 g Isotipendyl hydrochloride 10 g dl-methylephedrine hydrochloride 60 g Lactose 155 g Microcrystalline cellulose 145 g Magnesium stearate 10 g Hardened castor oil 10 g Example 2 The following components were weighed and thoroughly mixed, and then the same as in Example 1 Then, a tablet of 220 mg was obtained. Epradinone hydrochloride 75 g Diphenylpyraline hydrochloride 5 g Guaiphenesin 60 g Phenylpropanolamine 60 g Anhydrous caffeine 75 g Lactose 200 g Microcrystalline cellulose 200 g Magnesium stearate 10 g Hardened castor oil 10 g Example 3 The following components were weighed and mixed thoroughly. A 225 mg tablet was obtained according to Example 1. Epradinone hydrochloride 75 g Dipheterol hydrochloride 90 g dl-methylephedrine hydrochloride 60 g Lysozyme chloride 60 g (titer) Anhydrous caffeine 75 g Lactose 250 g Microcrystalline cellulose 250 g Magnesium stearate 20 g Hardened castor oil 10 g Example 4 The following components were weighed: After thorough mixing, 225 mg tablets were obtained according to Example 1. Eprazinone hydrochloride 75 g Promethazine hydrochloride 15 g dl-Methylephedrine hydrochloride 60 g Proxifylline 150 g Lysozyme chloride 60 g (titer) Anhydrous caffeine 75 g Lactose 250 g Microcrystalline cellulose 250 g Magnesium stearate 20 g Hardened castor oil 10 g Example 5 After weighing and thoroughly mixing, 250 mg tablets were obtained according to Example 1. Acetaminophen 750 g Noscapine 48 g Oxerazine citrate 60 g Tripelenamine hydrochloride 75 g Bromhexine hydrochloride 12 g Lactose 305 g Microcrystalline cellulose 300 g Magnesium stearate 10 g Hardened castor oil 10 g Example 6 The following components were weighed and thoroughly mixed, and then practiced. A 300 mg tablet was obtained according to Example 1. Ibuprofen 400 g Noscapine hydrochloride 36 g Oxerazine citrate 60 g Metilazine hydrochloride 8 g Ambroxol hydrochloride 45 g 1-methylephedrine hydrochloride 60 g Lysozyme chloride 90 g (titer) Anhydrous caffeine 75 g Lactose 248 g Low-substituted hydroxypropylcellulose 248 g Magnesium stearate oil 15 g Example 7 Preservatives, sweeteners and flavors were added to an aqueous solution in which a pH adjuster (phosphate buffer) was dissolved and completely dissolved, and the sucrose fatty acid ester was uniformly dispersed in the solution. After adding and dissolving acetaminophen and other components, purified water was added to adjust the total volume to 60 L, thereby producing the product. Acetaminophen 900g citric Okiserajin 60g alimemazine tartrate 7.2 g dl-methylephedrine hydrochloride ephedrine 60g bromhexine hydrochloride 12g of anhydrous caffeine 75g Vitamin _{B 1} nitrate 8g vitamin _B 2 4g sucrose fatty acid ester 14g Mannitol 14g stevia 10g ethyl benzoate 5g Orange Flavor 0.8 g Test Example [Effect of the combined preparation on cough symptoms] Test method Using a Hartley-type guinea pig weighing 350 g ± 50 g, freely ingesting feed and drinking water at a room temperature of 24 ± 1 ° C and reserve After rearing, they were subjected to experiments. A non-anesthetized guinea pig was placed in a body plethysmograph. The body plethysmograph consists of two clear acrylic cylindrical boxes (approximately 1.2 liters) for the head and body, and an acrylic necklace trainer covered with two upper and lower rubber films. The method of Kohrogi et al. (J. Clin. Invest. 82, 2063)
According to ~ 2068), capsaicin is sprayed from the upper part of the entire container with an ultrasonic nebulizer (TUR-3200, Nihon Kohden) for 2 minutes (2.2 mL / min), and the presence or absence of cough, the intensity and frequency of cough reflex are determined. Examined. The coughing sound was confirmed with a microphone, and the change in the internal pressure of the closed body box was recorded on a pen recorder via a flow meter (MEP-1100, Nihon Kohden). Evaluation was performed by using the index as to whether or not the number of occurrences of the cough reaction that occurred for one minute was suppressed. The room temperature was set at 25 ° C. As a comparative drug, a formulation shown in Table 1 dissolved in 50 mL of purified water was used. Each group consisted of 5 animals, and each group was orally administered 3 mL of the drug 30 minutes before exposure to capsaicin. (The control group received 3 mL of purified water.) Results Table 2 shows the results of the number of cough reactions and the rate of inhibition from the control group. The degree of suppression of the cough reaction was greater in the combination prescription group of the groups A to D than in the control group of the groups E to I, and it was proved that the above combination drugs had an excellent effect. [Table 2] The present invention is a composition having a dramatic effect on the elimination and alleviation of cough symptoms, since the antitussive effect of a cold or the like is enhanced. Thus, a drug that is extremely useful for cough symptoms can be provided.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 31/4439 A61K 31/4439 31/4465 31/4465 31/495 31/495 31/5415 31/5415 A61P 11/10 A61P 11/10 (72) Inventor Joji Nakagami 3- 24-1, Takada, Toshima-ku, Tokyo Inside Taisho Seiyaku Co., Ltd. (72) Inventor Katsuyoshi Aikawa 3- 24-1, Takada, Toshima-ku, Tokyo No. Taisho Pharmaceutical Co., Ltd. (72) Inventor Yasushi Nakagawa 3-24-1, Takada, Toshima-ku, Tokyo F-term within Taisho Pharmaceutical Co., Ltd. 4C086 AA01 AA02 BC17 BC21 BC50 CB05 CB29 GA07 GA08 GA10 GA12 MA02 MA04 NA05 ZA63 4C206 AA01 AA02 FA01 FA03 FA05 KA06 MA02 MA04 NA05 ZA63

Claims (1)

Claims: (1) At least one selected from the group consisting of (a) epradinone, oxerazine and salts thereof, and (b) isothipendyl, diphenylpyraline, diphenhydramine, dipheterol, triprolidine, tripelenamine, tondylamine, phenetazine, A pharmaceutical composition comprising one or more selected from methdilazine, carbinoxamine, alimemazine, mebuhydroline, promethazine, chlorpheniramine, iproheptin and salts thereof.