JP2010241834A - Pharmaceutical composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a pharmaceutical composition which is improved in effect for various symptoms accompanied by allergic rhinitis, cold, etc., particularly congested nose symptom by inflammation of tunica mucosa nasi. <P>SOLUTION: The pharmaceutical composition has (A) pseudoephedrine or its pharmaceutically permissible salt, (B) phenylephrine, methoxyphenamine or their pharmaceutically permissible salt, and (C) at least one kind selected from the group consisting of a Datura stramonium extract, belladonna total alkaloid, belladonna extract and scopolia extract. The pharmaceutical composition has pseudoephedrine, phenylephrine or methoxyphenamine, and at least one kind selected from the group consisting of a stramonium extract, belladonna total alkaloid, belladonna extract and scopolia extract. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a pharmaceutical composition. More specifically, the present invention relates to a pharmaceutical composition excellent in improving nasal inflammation such as nasal congestion caused by virus or fungal infection or reaction to allergy.

  Rhinitis is a disease whose main symptoms are sneezing, aqueous nasal discharge (nasal mucus), nasal itching and nasal congestion (nasal congestion), and it is infected with viruses and bacteria, and foreign substances such as pollen and house dust are in the nasal cavity. Symptoms appear due to entering the. There are many causes of rhinitis, including those caused by infection with viruses, bacteria, and fungi, and those caused by pollen and house dust allergies. Because the cause therapy of rhinitis is difficult and time consuming, coping therapy to relieve symptoms is mainly performed as a treatment for rhinitis.

Parasympathetic blockades such as belladonna total alkaloids, funnel extracts, and isopropamide iodide are used to improve nasal inflammation because they reduce secretion of nasal mucus. Furthermore, a composition for treating rhinitis (Patent Document 1) is known in which anti-allergic agents such as emedastine and ebastine are mixed with these parasympathomimetic drugs and have an enhanced nasal secretion suppression effect.
However, among nasal inflammation symptoms, inflammatory symptoms accompanied by swelling of the nasal mucosa (nasal obstruction symptoms) are difficult and difficult to breathe for the patient. Therefore, from the viewpoint of the patient's QOL and respiratory infections such as colds. Early improvement is also desired from the viewpoint of prevention. As a nasal congestion relieving component, sympathomimetic drugs such as phenylpropanolamine, pseudoephedrine, methylephedrine, phenylephrine are mainly used, and rhinitis containing phenylpropanolamine hydrochloride or phenylephrine hydrochloride and mequitazine or astemizole A therapeutic composition (Patent Document 2) is known. However, a satisfactory pharmaceutical composition for improving nasal congestion has not been obtained.

  As described above, there is no agent for improving nasal congestion caused by allergic rhinitis or the like, and there is still a need for a safer and more effective therapeutic agent and method without expecting sufficient action.

JP 2002-338486 A Japanese Patent Laid-Open No. 07-188002

  An object of the present invention is to provide a pharmaceutical composition for treating rhinitis which has an excellent effect on nasal congestion.

The inventors of the present invention have made extensive studies to solve the above problems, and are composed of (A) pseudoephedrine, (B) phenylephrine or methoxyphenamine, and (C) datsura extract, belladonna total alkaloid, belladonna extract, funnel extract. When used in combination with at least one selected from the group, it was found that a remarkable effect of improving nasal congestion was achieved compared to when each was used alone, and the present invention was completed.
That is, this invention is the pharmaceutical composition or nasal congestion improvement method hung up below.
(1) (A) pseudoephedrine or a pharmaceutically acceptable salt thereof, (B) phenylephrine or methoxyphenamine or a pharmaceutically acceptable salt thereof, and (C) datsura extract, belladonna total alkaloid, belladonna extract, funnel extract A pharmaceutical composition comprising at least one selected from the group consisting of:
(2) The pharmaceutical composition according to (1), which is used for rhinitis or cold.
(3) The pharmaceutical composition according to (1) or (2), further comprising at least one selected from an antihistamine, an anti-inflammatory enzyme, an anti-inflammatory drug, and xanthines.
(4) The pharmaceutical composition according to any one of (1) to (3), which is an agent for improving nasal congestion.
(5) (A) Pseudoephedrine or a pharmaceutically acceptable salt thereof, (B) phenylephrine or methoxyphenamine or a pharmaceutically acceptable salt thereof, and (C) datsura extract, belladonna total alkaloid, belladonna extract, funnel extract A method for improving nasal congestion comprising using at least one selected from the group consisting of:
In the present specification, “%” means “W / W%” unless otherwise specified.

  According to the present invention, (A) pseudoephedrine or a pharmaceutically acceptable salt thereof, (B) phenylephrine or methoxyphenamine or a pharmaceutically acceptable salt thereof, and (C) datsura extract, belladonna total alkaloid, belladonna extract By containing at least one selected from the group consisting of funnel extracts, the action of improving nasal congestion is remarkably excellent, and thus a pharmaceutical composition having a high therapeutic effect is provided.

  The pharmaceutical composition of the present invention comprises (A) pseudoephedrine or a pharmaceutically acceptable salt thereof, (B) phenylephrine or methoxyphenamine or a pharmaceutically acceptable salt thereof, and (C) datsura extract, belladonna total alkaloid, It contains at least one selected from the group consisting of belladonna extract and funnel extract, and an unexpectedly high nasal obstruction improvement effect can be obtained as compared with the case where these are used alone.

The dose of pseudoephedrine or a pharmacologically acceptable salt thereof in the present invention 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 5 mg. Above, preferably 15 mg or more, more preferably 30 mg or more. In addition, the upper limit is 300 mg or less, preferably 240 mg or less, more preferably 180 mg or less in consideration of pharmacological effects and side effects. 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. The content of pseudoephedrine or a pharmacologically acceptable salt thereof in the pharmaceutical composition of the present invention can be determined by appropriately selecting the dosage form (form or size), patient, etc. in consideration of the dose. it can. The pseudoephedrine may be any of d-form, l-form or dl-form.

The dose of phenylephrine or a pharmacologically acceptable salt thereof in the present invention is not particularly limited as long as it is a range that is usually used in the art, but in the case of oral administration, the dose per day for an adult is 4 mg or more. , Preferably 5 mg or more, more preferably 6 mg or more. In addition, the upper limit is 50 mg or less, preferably 40 mg or less, more preferably 30 mg or less in consideration of pharmacological effects and side effects. 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. The content of phenylephrine or a pharmacologically acceptable salt thereof in the pharmaceutical composition of the present invention can be determined by appropriately selecting the dosage form (form or size), patient, etc. in consideration of the dose. .
In the present invention, the blending ratio of pseudoephedrine and phenylephrine is not particularly limited as long as the effects of the present invention are achieved, but in consideration of economy and dose, phenylephrine is usually 1 per 100 parts by weight of pseudoephedrine. It can be added in a proportion of not less than 3 parts by weight, preferably not less than 3 parts by weight, particularly preferably not less than 7 parts by weight, usually not more than 110 parts by weight, preferably not more than 100 parts by weight, particularly preferably not more than 90 parts by weight.

The dose of methoxyphenamine or a pharmacologically acceptable salt thereof in the present invention 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 It is 10 mg or more, preferably 20 mg or more, more preferably 30 mg or more. The upper limit is 200 mg or less, preferably 180 mg or less, more preferably 150 mg or less in consideration of pharmacological effects and side effects. 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. The content of methoxyphenamine or a pharmacologically acceptable salt thereof in the pharmaceutical composition of the present invention should be determined by appropriately selecting the dosage form (form or size), patient, etc. in consideration of the dose. Can do.
In the present invention, the blending ratio of pseudoephedrine and methoxyphenamine is not particularly limited as long as the effects of the present invention are achieved, but considering the economy and dose, methoxyphenamine is added to 1 part by weight of pseudoephedrine. Is usually 0.05 parts by weight or more, preferably 0.10 parts by weight or more, particularly preferably 0.15 parts by weight or more, usually 6 parts by weight or less, preferably 5 parts by weight or less, particularly preferably 4 parts by weight. It can mix | blend in the following ratios.

  Pseudoephedrine, phenylephrine, and methoxyphenamine used in the present invention may be pharmaceutically acceptable salts. Examples of such salts include hydrochloride, hydrobromide, nitrate, sulfate, phosphate, oxalate, maleate, fumarate, and the like, such as hydrochloride, nitrate, or sulfate. Is particularly preferred.

  Datsura extract, belladonna total alkaloid, belladonna extract, funnel extract (hereinafter collectively referred to as “alkaloids”) in the present invention are not particularly limited as long as they are usually used in the technical field, but are particularly limited to the production of pharmaceuticals. What can be used as a raw material is preferable. In the present invention, 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 produced using an appropriate extractant such as ethanol, ether, or water. , Here represents both Belladonna alkaloids and Belladonna total alkaloids. The dose of alkaloids is not particularly limited as long as it is a range usually used in the art, but in the case of oral administration, the daily dose for adults is usually 0.08 mg as the total alkaloid amount in datsura extract. Or more, preferably 0.10 mg or more, 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. For belladonna total alkaloids, 0.08 mg or more, preferably 0.10 mg or more, 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, and belladonna extract and For funnel extracts, it is usually at least 8 mg, preferably at least 10 mg, particularly preferably at least 12 mg , And the normal 80mg or less on the upper limit, preferably 70mg or less, particularly preferably not more than 60 mg. 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. The content of alkaloids in the pharmaceutical composition of the present invention can be determined by appropriately selecting the dosage form (form or size), patient, etc. in consideration of the dose.

  In the present invention, the blending ratio of pseudoephedrine and alkaloids is not particularly limited as long as the effects of the present invention are achieved, but in consideration of economy and dose, datsura extract with respect to 100 parts by weight of pseudoephedrine, The total amount of alkaloid is usually 0.05 parts by weight or more, preferably 0.10 parts by weight or more, particularly preferably 0.15 parts by weight or more, usually 5 parts by weight or less, preferably 2 parts by weight or less, particularly preferably In a proportion of 1 part by weight or less, the total belladonna alkaloid is usually 0.05 parts by weight or more, preferably 0.10 parts by weight or more, particularly preferably 0.15 parts by weight or more, usually 5 parts by weight or less, preferably 2 parts by weight or less, particularly preferably 1 part by weight or less, and for belladonna extract and funnel extract, usually 4 parts by weight or more Preferably 6 parts by weight or more, particularly preferably 8 parts by weight or more, usually 220 parts by weight or less, preferably 200 parts by weight or less, particularly preferably be in a proportion of less than 180 parts by weight.

  In the present invention, the blending ratio of phenylephrine or methoxyphenamine and alkaloids is not particularly limited as long as the effects of the present invention are exhibited. However, in view of economy and dosage, for example, phenylephrine or methoxyphenamine 100 In the duck extract, the total alkaloid amount is usually 0.05 parts by weight or more, preferably 0.10 parts by weight or more, particularly preferably 0.15 parts by weight or more, usually 20 parts by weight or less, Is a ratio of 10 parts by weight or less, particularly preferably 5 parts by weight or less, and for belladonna total alkaloids, usually 0.05 parts by weight or more, preferably 0.10 parts by weight or more, particularly preferably 0.15 parts by weight or more, Usually 20 parts by weight or less, preferably 10 parts by weight or less, particularly preferably 5 parts by weight or less, belladonna extract And funnel extract, usually 4 parts by weight or more, preferably 6 parts by weight or more, particularly preferably 8 parts by weight or more, usually 220 parts by weight or less, preferably 200 parts by weight or less, particularly 180 parts by weight or less. be able to.

For the present invention, an antihistamine is preferably contained or used in combination. Antihistamines include, for example, chlorpheniramine, clemastine, diphenhydramine, iproheptin, isothipentyl, dipheterol, diphenylpyralin, triprolidine, tripelenamine, tondilamine, promethazine, methodirazine, carbinoxamine, alimemazine, promethazine, mebhydrolin, phenethazine, phenethazine, Oxatomide, mequitazine, terfenadine, epinastine, astemizole, ebastine, cetirizine, levocabastine, olopatadine, cromoglycic acid, tranilast, amlexanox, ibudilast, pemirolast, tazanolast, emedastine and pharmacologically acceptable salts thereof (e.g. maleic acid Lamin, diphenhydramine hydrochloride, fuma Ketotifen, clemastine fumarate, azelastine hydrochloride, levocabastine hydrochloride, sodium cromoglycate, fumaric acid emedastine), and others.
The antihistamine in the present invention is not particularly limited as long as it is a range that is usually used in the technical field, but it is usually 1 mg or more, preferably 3 mg or more per day for an adult, and the upper limit is further a dose or pharmacological action. Is 200 mg or less, preferably 150 mg or less, depending on the type of antihistamine. Further, the effect of the antihistamine in the present invention is usually 0.01 parts by weight or more, preferably 0.015 parts by weight or more, with respect to 1 part by weight of pseudoephedrine. In addition, the upper limit is usually 10 parts by weight or less, preferably 3 parts by weight or less, considering dose and pharmacological action. However, the upper limit depends on the type of antihistamine, and is particularly limited to these. is not.

In contrast to the present invention, when an anti-inflammatory enzyme or an anti-inflammatory drug is contained or used in combination, inflammation of the nasal mucosa is suppressed, which is more preferable. Anti-inflammatory enzymes or anti-inflammatory drugs include lysozyme, serrapeptase, bromelain, semi-alkaline proteinase, pronase, glycyrrhizic acid, glycyrrhetinic acid, allantoin, azulene, azulene sulfonic acid, tranexamic acid, epsilon-aminocaproic acid, berberine, indomethacin, diclofenac, prano Examples include profen, piroxicam and pharmacologically acceptable salts (for example, lysozyme chloride, dipotassium glycyrrhizinate, ammonium glycyrrhizinate, sodium azulenesulfonate, berberine chloride, berberine sulfate, diclofenac sodium, etc.).
The anti-inflammatory enzyme or anti-inflammatory drug in the present invention is not particularly limited as long as it is a range that is usually used in the technical field, but lysozyme chloride is 18 mg to 90 mg (titer) and bromelain is 24 per day for an adult. Thousands of units to 120,000 units and glycyrrhizic acid may be 20 mg to 200 mg. Further, in the present invention, an effect can be obtained if the ratio of the anti-inflammatory enzyme or the anti-inflammatory drug is usually 0.05 parts by weight or more with respect to 1 part by weight of pseudoephedrine, preferably 0.1 parts by weight or more. . In addition, the upper limit is usually 10 parts by weight or less, preferably 8 parts by weight or less, considering dose and pharmacological action. However, the upper limit depends on the kind of anti-inflammatory enzyme or anti-inflammatory drug, and is particularly limited thereto. Is not to be done.

For the present invention, a xanthine derivative is preferably contained or used in combination. Examples of xanthine derivatives include caffeine, theophylline, theobromine, diprofylline, proxyphylline, pentoxifylline or a salt thereof, sodium benzoate caffeine, etc., preferably caffeine, sodium benzoate caffeine, etc. Or may be anhydrous.
The xanthine derivative in the present invention is not particularly limited as long as it is a range that is usually used in the technical field, but it is usually 30 mg or more, preferably 60 mg or more per day for both adults and combined use. Furthermore, considering dose and pharmacological action, it may be 300 mg or less, preferably 150 mg or less, but also depends on the type of xanthine derivative. Further, in the composition of the present invention, this effect can be obtained if the ratio of the xanthine derivative is usually 10 parts by weight or more with respect to 100 parts by weight of pseudoephedrine, and preferably 30 parts by weight or more. Further, the upper limit is usually 1000 parts by weight or less, preferably 500 parts by weight or less, considering dose and pharmacological action, but is not particularly limited thereto.

  For the present invention, various components (including pharmacologically active components and physiologically active components) can be contained or used in combination as required. The kind of such components is not particularly limited, and examples thereof include antipyretic analgesics, sedative hypnotics, antitussives, expectorants, vitamins, mucosal protective components, and refreshing components. Examples of suitable components in the present invention include the following components.

  Antipyretic analgesic ingredients: for example, aspirin, aspirin aluminum, acetaminophen, etenzamide, sazapyrine, salicylamide, sodium salicylate, lactylphenetidine, ibuprofen and ketoprofen.

Sedative hypnotic ingredients: for example, bromvalerylurea, allylisopropylacetylurea, etc.
Antitussive ingredients: achloramide, cloperastine, pentoxyberine (carbetapentane), tipepidine, dibutate, dextromethorphan, codeine, dihydrocodeine, noscapine and their pharmacologically acceptable salts (eg cloperastine hydrochloride, tipepidine hibenzate) Dextromethorphan hydrobromide, codeine phosphate, dihydrocodeine phosphate, noscapine hydrochloride, etc.).
Expectorants: potassium guaiacol sulfonate, guaifenesin, etc.

  Vitamins: For example, vitamins A [for example, retinal, retinol, retinoic acid, carotene, dehydroretinal, lycopene and pharmacologically acceptable salts thereof (for example, retinol acetate, retinol palmitate, etc.), vitamin B [E.g. thiamine, thiamine disulfide, dicetiamine, octothiamine, chicotiamine, bisbutiamine, bisbenchamine, prosultiamine, benfotiamine, fursultiamine, riboflavin, flavin adenine dinucleotide, pyridoxine, pyridoxal, hydroxocobalamin, Cyanocobalamin, methylcobalamin, deoxyadenocobalamin, folic acid, tetrahydrofolic acid, dihydrofolic acid, nicotinic acid, nicotinamide, nicotinyl alcohol, pantothenic acid, Tentenol, biotin, choline, inositol or pharmacologically acceptable salts thereof (for example, thiamine hydrochloride, thiamine nitrate, dicetiamine hydrochloride, fursultiamine hydrochloride, riboflavin butyrate, sodium riboflavin phosphate, sodium flavin adenine dinucleotide, Pyridoxine hydrochloride, pyridoxal phosphate, pyridoxal calcium phosphate, hydroxocobalamin hydrochloride, hydroxocobalamin acetate, calcium pantothenate, sodium pantothenate, etc.), vitamin C [eg ascorbic acid, erythorbic acid, derivatives thereof or pharmacology thereof] Acceptable salts (for example, sodium ascorbate, sodium erythorbate, etc.)], vitamin D [for example, ergocalciferol, cholecalci Errol, hydroxycholecalciferol, dihydroxycholecalciferol, dihydrotaxosterol and pharmacologically acceptable salts thereof, etc.], vitamin E [for example, tocopherol and its derivatives, ubiquinone derivatives and their pharmacologically acceptable Salts (tocopherol acetate, tocopherol nicotinate, tocopherol succinate, tocopherol calcium succinate, etc.)], other vitamins [eg hesperidin, carnitine, ferulic acid, γ-oryzanol, orotic acid, rutin, eriocitrin and Pharmacologically acceptable salts thereof (such as carnitine chloride)].

  Mucosal protective component: For example, aminoacetic acid, dry aluminum hydroxide gel, aluminum-based mucosal protective agent such as dihydroxyaluminum / aminoacetate, magnesium aluminate metasilicate, aluminum silicate, hydrotalcite, alumina magnesium hydroxide, hydroxylated Aluminum gel, aluminum hydroxide / sodium bicarbonate coprecipitation product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / calcium carbonate / magnesium carbonate coprecipitation product, magnesium carbonate, magnesium oxide, magnesium hydroxide Magnesium-based mucosal protective agents such as coprecipitation products of magnesium silicate, magnesium hydroxide and potassium aluminum sulfate.

  Cooling components: for example, l-menthol, d-menthol, dl-menthol, d-camphor, dl-camphor, d-borneol, dl-borneol, geraniol, eucalyptus oil, bergamot oil, fennel oil, peppermint oil, cinnamon oil Essential oils such as rose oil and peppermint oil and essential oil components.

The pharmaceutical composition of the present invention can be formulated by arbitrarily selecting various components and additives used for pharmaceuticals, quasi drugs and the like according to the form of the preparation. For example, for solid preparations, binders (hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, etc.), excipients (sucrose, lactose, starch, corn starch, crystalline cellulose, light anhydrous Silicic acid etc.), lubricants (sucrose fatty acid ester, magnesium stearate etc.), disintegrating agents (methyl cellulose, polysorbate 80, croscarmellose sodium etc.), foaming agents (sodium hydrogen carbonate etc.) etc. can be used. Moreover, in a semi-solid preparation, a base according to the type of preparation, for example, an ointment base (for example, petrolatum,
Hydrocarbon bases such as liquid paraffin and wax, cetanol, higher fatty acid esters, etc., gel bases (eg, carboxyvinyl polymer, gum), oily bases (vegetable oils such as olive oil, soybean oil, sesame oil, cottonseed oil) Etc.) can be used. Furthermore, in the solution, a solvent or water as a base, an oily base, a solubilizing agent, a suspending or emulsifying agent, an isotonic agent, a buffering agent and the like can be used. Moreover, you may add antiseptic | preservative, antioxidant, a sweetener, a sour agent, a coloring agent, a fragrance | flavor, a flavoring agent, etc. to these compositions as needed.

In this invention, the dosage form or usage form of a pharmaceutical composition is not specifically limited, According to the use or kind of composition, various dosage forms or usage forms can be taken.
Examples of the dosage form include solid dosage forms, semi-solid dosage forms, or liquid dosage forms, preferably solid dosage forms. Specifically, tablets (including intraoral quick disintegrating tablets, chewable tablets, effervescent tablets, troches, jelly drops, etc.), granules, fine granules, powders, hard capsules, soft capsules, Examples include liquids, gels, liposomes, extracts, tinctures, lemonades, syrups, dry syrups, jellies, suspensions, etc. Particularly preferred are tablets, granules, fine granules, powders, hard capsules. Agents, soft capsules, dry syrups, solutions, and suspensions. These compositions are prepared by a conventional method, and in this case, in addition to the above-described components, conventional additives corresponding to the preparation can be used.

  The use of the pharmaceutical composition of the present invention includes, for example, for rhinitis, cold, etc. Specifically, for rhinitis, allergic rhinitis, acute rhinitis, sinus due to sinusitis, sneezing, nasal congestion, etc. For the treatment or alleviation of cold, cold symptoms, cold symptoms (sore throat, fever, chills, headache, joint pain, muscle pain, cough, sputum, sneezing, runny nose, stuffy nose, etc.) It can be used in a composition for treatment or alleviation.

  (A) Pseudoephedrine of the present invention or a pharmaceutically acceptable salt thereof, (B) phenylephrine or methoxyphenamine or a pharmaceutically acceptable salt thereof, and (C) datsura extract, belladonna total alkaloid, belladonna extract, funnel extract The method for improving nasal congestion comprising the combined use of at least one selected from the group consisting of these is implemented by appropriately formulating and administering these components. In the method of the present invention, pseudoephedrine, phenylephrine, methoxyphenamine, datsura extract, belladonna total alkaloid, belladonna extract, funnel extract are the same as those used in the above invention or the above composition, and pharmaceutically acceptable salts and uses Individual doses and ratios are also the same as above. Further, in this method, (A) pseudoephedrine, (B) phenylephrine or methoxyphenamine, and (C) datsura extract, belladonna total alkaloid, belladonna extract, funnel extract are used in combination. As for the method, a known or commonly used preparation or administration method can be used depending on each component.

Hereinafter, the present invention will be described in more detail based on Examples and Comparative Examples, but the present invention is not limited to these Examples and Comparative Examples.
Test Example Test on improvement of nasal congestion Tablets were produced according to the prescription shown in Table 1 in accordance with the Japanese Pharmacopoeia (general formulation “Tablet”), and the nasal congestion improvement effects of Examples and Comparative Examples were evaluated. For 25 patients with nasal congestion (nasal congestion), divide 5 patients each into 5 groups and take the preparations of the example or comparative example 2 tablets at a time, 3 times a day, within 30 minutes after meal The degree of improvement of nasal congestion after 30 minutes, 1 hour, and 3 hours after taking was evaluated according to the following evaluation criteria. The results are shown in Table 2.
(Evaluation criteria for improvement in nasal congestion)
5: Symptom disappeared 4: Slightly remained 3: Slightly improved 2: Unchanged 1: Deteriorated

  In the belladonna total alkaloid administration group (Comparative Example 2), almost no improvement in nasal congestion was observed, and in the phenylephrine hydrochloride and pseudoephedrine hydrochloride administration group (Comparative Example 1), a slight nasal closure improvement effect was observed, but phenylephrine hydrochloride, In the pseudoephedrine hydrochloride and belladonna total alkaloid administration group (Example 1), a further excellent effect of improving nasal congestion was observed. Moreover, in the pseudoephedrine hydrochloride administration group (Comparative Example 3), it takes time to develop the effect of improving nasal congestion, and in the phenylephrine hydrochloride administration group (Comparative Example 4), the effect of improving nasal congestion is exhibited in a short time after taking. But it didn't last. From this result, it was found that belladonna total alkaloids enhance the nasal closure improving effect of phenylephrine hydrochloride and pseudoephedrine hydrochloride.

The following examples illustrate formulation examples of the composition of the present invention.
Example 2 (tablets)
Pseudoephedrine hydrochloride 180 g
Phenylephrine hydrochloride 15 g
Belladonna Total Alkaloid 0.12g
Mequitazine hydrochloride 4 g
Anhydrous caffeine 150 g
Dipotassium glycyrrhizinate 200 g
Lactose 729.88g
Microcrystalline cellulose 465 g
Hydroxypropylcellulose 50 g
Magnesium stearate 6 g
The above ingredients were prepared according to the Japanese Pharmacopoeia General Formula “Tablet” and tableted to give 200 mg per tablet to obtain tablets. In addition, this preparation takes 9 tablets as an adult daily dose.

Example 3 (tablets)
Pseudoephedrine hydrochloride 120 g
Phenylephrine hydrochloride 30 g
Belladonna Total Alkaloid 0.2 g
Epinastine hydrochloride 4 g
Saishin extract 30 g
Anhydrous caffeine 150 g
Dipotassium glycyrrhizinate 100 g
Lactose 466.3 g
255 g microcrystalline cellulose
Hydroxypropylcellulose 40 g
Magnesium stearate 4.5 g
The above ingredients were prepared according to the Japanese Pharmacopoeia General Formula “Tablet” and tableted to give 200 mg per tablet to obtain tablets. In this preparation, take 6 tablets as a daily dose for an adult.

Example 4 (tablets)
Pseudoephedrine hydrochloride 60 g
150 g of methoxyphenamine hydrochloride
Belladonna Total Alkaloid 0.4 g
d-Chlorpheniramine maleate 6 g
Anhydrous caffeine 120 g
Dipotassium glycyrrhizinate 60 g
Lactose 214.6 g
Microcrystalline cellulose 110 g
Hydroxypropylcellulose 26 g
Magnesium stearate 3 g
The above ingredients were prepared according to the Japanese Pharmacopoeia General Rules for Tablets “Tablets”, and tableted to give 250 mg per tablet to obtain tablets. In this preparation, take 3 tablets as a daily dose for adults.

Example 5 (chewable agent)
Pseudoephedrine hydrochloride 180 g
Phenylephrine hydrochloride 10 g
Belladonna Total Alkaloid 0.4 g
d-Chlorpheniramine maleate 6 g
Anhydrous caffeine 150 g
Lysozyme chloride 75 g
Xylitol 1000 g
Aspartame 50 g
Microcrystalline cellulose 262.6 g
Hydroxypropylcellulose 60 g
Magnesium stearate 6 g
The above ingredients were prepared according to the Japanese Pharmacopoeia General Formula “Tablet” and compressed to 600 mg per tablet to obtain a chewable preparation. In this preparation, take 3 tablets as a daily dose for adults.

Example 6 (granule)
Pseudoephedrine hydrochloride 120 g
Phenylephrine hydrochloride 15 g
Belladonna Total Alkaloid 0.4 g
dl-chlorpheniramine maleate 12 g
Anhydrous caffeine 150 g
Dipotassium glycyrrhizinate 90 g
D-mannitol 1892.6 g
Low substituted hydroxypropylcellulose 600 g
Cornstarch 600 g
Hydroxypropylcellulose 120 g
The above ingredients were produced according to the Japanese Pharmacopoeia General Rules for Preparation of “Granules” and were packaged to give 1200 mg per capsule to obtain granules. In addition, take 3 capsules as a daily dose for adults.

Example 7 (tablet)
Pseudoephedrine hydrochloride 144 g
Phenylephrine hydrochloride 6 g
Belladonna Total Alkaloid 0.6 g
d-Chlorpheniramine maleate 6 g
Anhydrous caffeine 120 g
Dipotassium glycyrrhizinate 60 g
Lactose 868.4 g
Cornstarch 200 g
Hydroxypropylcellulose 30 g
Magnesium stearate 5 g
The above ingredients were manufactured according to the Japanese Pharmacopoeia General Rules for Tablets “Tablets” and manufactured to give 240 mg per tablet to obtain tablets. In this preparation, take 6 tablets as a daily dose for an adult.

Example 8 (hard capsule)
Pseudoephedrine hydrochloride 120 g
Phenylephrine hydrochloride 30 g
Datsura extract 0.2 g (as total alkaloids)
Emedastine hydrochloride 6 g
Anhydrous caffeine 120 g
Lysozyme chloride 75 g
Lactose 530 g
Microcrystalline cellulose 313.8 g
Magnesium stearate 5 g
The above ingredients were prepared according to the Japanese Pharmacopoeia General Formula “Capsule” and were prepared so that the internal volume per capsule was 200 mg to obtain a capsule. This preparation takes 6 capsules as a daily dose for an adult.

Example 9 (soft capsule)
Pseudoephedrine hydrochloride 60 g
Phenylephrine hydrochloride 15 g
Belladonna Total Alkaloid 0.4 g
d-Chlorpheniramine maleate 6 g
Anhydrous caffeine 120 g
Dipotassium glycyrrhizinate 60 g
Polysorbate 80 300 g
Glycerin fatty acid ester 39 g
Sara honey beeswax 259.6 g
Medium chain fatty acid triglyceride 40 g
The above ingredients were prepared according to the Japanese Pharmacopoeia General Formula “Capsule”, and the capsules were made so that the internal volume per capsule was 300 mg to obtain soft capsules. In addition, this preparation takes 3 capsules as a daily dose for an adult.

Example 10 (tablets)
Pseudoephedrine hydrochloride 120 g
Phenylephrine hydrochloride 30 g
Rohto extract 60 g
Epinastine hydrochloride 4 g
Saishin extract 30 g
Anhydrous caffeine 150 g
Dipotassium glycyrrhizinate 100 g
Lactose 466.3 g
Microcrystalline cellulose 195.2 g
Hydroxypropylcellulose 40 g
Magnesium stearate 4.5 g
The above ingredients were prepared according to the Japanese Pharmacopoeia General Formula “Tablet” and tableted to give 200 mg per tablet to obtain tablets. In this preparation, take 6 tablets as a daily dose for an adult.

Example 11 (hard capsule)
Pseudoephedrine hydrochloride 120 g
Phenylephrine hydrochloride 30 g
Belladonna extract 20 g
Emedastine hydrochloride 6 g
Anhydrous caffeine 120 g
Lysozyme chloride 75 g
Lactose 530 g
Microcrystalline cellulose 294 g
Magnesium stearate 5 g
The above ingredients were prepared according to the Japanese Pharmacopoeia General Formula “Capsule” and were prepared so that the internal volume per capsule was 200 mg to obtain a capsule. This preparation takes 6 capsules as a daily dose for an adult.

Claims (1)

(A) Pseudoephedrine or a pharmaceutically acceptable salt thereof, (B) phenylephrine or methoxyphenamine or a pharmaceutically acceptable salt thereof, and (C) datsura extract, belladonna total alkaloid, belladonna extract, funnel extract A pharmaceutical composition comprising at least one selected from the above.