JP2002338486A - Composition for common cold and rhinitis - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition for common cold and rhinitis having improved effect on excessive secretion of nasal mucus accompanying to common cold syndrome, rhinitis, etc. SOLUTION: The composition for common cold and rhinitis effective for stopping or mitigating the secretion of nasal mucus is produced by using (a) an antiallergic agent selected from emedastine, ebastine, ramatroban, bepotastine and their salts and (b) a parasympatholytic drug selected from belladonna (total) alkaloid, belladonna extract, scopolia extract, isopropamide iodide and datura extract as active ingredients.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for colds and rhinitis which has an improved effect on nasal hyperplasia (nose nose) caused by cold syndrome or rhinitis.

[0002]

2. Description of the Related Art Emedastine, ebastine, ramatroban and bepotastine are used as antiallergic drugs, and belladonna (total) alkaloids, belladonna extract, funnel extract, isopropamide iodide and datsura extract are widely and widely used as parasympathetic nerve blockers. Is a drug that has been used. As such, various kinds of drugs are known, and antiallergic drugs such as emedastine, ebastine, ramatroban, and bepotastine, and parasympathomimetic drugs such as belladonna (total) alkaloids, belladonna extract, funnel extract, isopropamide iodide, and datura extract. No composition is known which combines On the other hand, a number of compositions for cold and rhinitis have been known so far, but none of them have sufficient effects on nasal hyperplasia, a nasal mucosa hypersecretion lesion associated with cold syndrome, etc. No effect was obtained.

[0003]

The cold syndrome is a respiratory infection. Generally, it is a disease accompanied by various systemic symptoms such as malaise and local inflammatory symptoms mainly in the upper respiratory tract. Although the development of a drug having an antiviral effect to suppress the infection and proliferation of the virus that causes a cold is desired as a causative therapy, at present the state of the art is still developing effective ones. Rather, symptomatic treatments aimed at improving individual symptoms are at the center of cold treatment. The same applies to those caused by bacterial infection. Furthermore, it has been pointed out that the increase in allergic predisposing factors has reduced the resistance from chronic and persistent inflammation of the respiratory tract, and has liable to cause respiratory infections. However, improvement of allergy or atopic constitution
At present, no simple and effective method has been found in a short period of time, and symptomatic treatment aimed at improving individual symptoms is also the mainstay of treatment.

[0004] The core of symptomatic treatment is relief of various symptoms by antipyretic analgesic components, antitussive components, bronchodilator components, etc. Belladonna (total) alkaloids, belladonna extract, funnel extract, isopropamide iodide, datura extract and the like. Are originally used for such purposes. Therefore, particularly in the medical setting, the use of the combination formulation has not been performed. However, since colds and rhinitis are accompanied by various symptoms at the same time when they become ill, it is necessary to cure various symptoms early, reduce the frequency of drug use and prevent the occurrence of side effects. It has been desired to develop a compounding agent in which the amount of components is reduced and the effect is enhanced, and it has been important how to formulate a compound that achieves such purpose.

[0005] Particularly in daily life, among the various symptoms caused by a cold, nasal overuse symptoms, especially nasal symptoms, cause respiratory insufficiency, disturb the concentration of things and cause an unexpected accident. Not only have the danger of causing
Must be compensated by oral respiration and the direct uptake of fresh air into the lungs can lead to secondary infections with new viruses and bacteria, leading to the disadvantage of prolonged symptoms. This is exactly the same in the case of nasal overdose caused by allergic rhinitis. In other words, how to remove nasal overdose symptoms as early as possible and prevent new secondary infections or sensitization of allergens beforehand to relieve or cure the symptoms is an important point in the actual treatment. ing.

The present invention has therefore been made in view of the above-mentioned prior art, and has as its object a viral cold,
Bacterial cold, influenza, tonsillitis, allergies,
An object of the present invention is to provide a composition for colds and rhinitis, which can reliably eliminate or reduce symptoms of excessive nasal discharge (nose nose) among various symptoms caused by hay fever and atopy.

[0007]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies for the purpose described above, and as a result, by combining a specific antiallergic agent and a parasympathetic blocker as active ingredients, nasal mucosa of the nasal mucosa was increased. The present invention has been found to have a dramatic effect on the elimination or alleviation of nasal symptoms, and the present invention has been completed. That is, the present invention provides (a) a component: at least one selected from the group consisting of emedastine, ebastine, ramatroban, bepotastine and salts thereof, and (b) a component: belladonna (total) alkaloid, belladonna extract, funnel extract, A composition for colds and rhinitis, comprising at least one selected from the group consisting of isopropamide iodide and datura extract, wherein the composition is for removing or reducing nasal secretion.

In the present invention, the belladonna (total) alkaloid refers to both a belladonna alkaloid or a belladonna total alkaloid, and is an alkaloid extracted from a herbal medicine belladonna (Atoropa belladonna Linne). In the present invention, the salts are hydrochlorides,
Nitrate, sulfate, phosphate, oxalate, maleate, fumarate, tosylate, besylate, hydrobromide and the like can be mentioned.

The composition for treating cold and rhinitis of the present invention comprises:
Usually, it can be orally administered to an adult once or several times a day. This dose depends on age, weight,
It can be increased or decreased as appropriate depending on the condition. The amount of emedastine or a salt thereof is preferably 0.5 to 5 mg, preferably 1 to 4 mg, and ebastine or a salt thereof is preferably 1.25 to 15 mg, and preferably 2.5, per day for each adult. Ramatroban or a salt thereof is preferably 15 to 200 mg, preferably 3 to 200 mg.
The dose is preferably 7.5 to 150 mg, and bepotastine or a salt thereof is preferably 2.5 to 25 mg, and more preferably 5 to 20 mg. Similarly, the belladonna (total) alkaloid is preferably from 0.06 to 1.0 mg, and more preferably from 0.1 to 0.6 mg.
g is good, belladonna extract is good 6 ~ 100mg,
Preferably, 10 to 60 mg is good, and the funnel extract is 6 to
100 mg is good, preferably 10-60 mg,
The amount of iodide isopropamide is preferably 0.75 to 10 mg, preferably 1.0 to 7.5 mg, and the datura extract is 0.7.
The amount is preferably from 0.6 to 1.0 mg, preferably from 0.1 to 0.6 mg.
Is good. The amount of each component (b) is usually 0.0003 parts by mass or more, preferably 0.0006 to 60 parts by mass, per 1 part by mass of component (a).

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION The composition for colds and rhinitis of the present invention can be prepared in the form of tablets, capsules, granules, fine granules, powders, chewables, foaming agents, drops, dissolving agents in the mouth,
It is used as a preparation for oral administration such as dry syrup and oral liquid. These preparations can be prepared by a conventional method. In solid preparations, carriers used for preparation of the preparation include lactose, starch, sugar, mannitol, excipients such as crystalline cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, gelatin,
There are binders such as PVP, disintegrators such as carboxymethylcellulose calcium and low-substituted hydroxypropylcellulose, and lubricants such as magnesium stearate, hydrogenated castor oil, and talc. , Preservatives, flavors, pigments, flavoring agents and the like can be used.

[0011] In the oral liquid preparation, carriers used for preparation of the preparation include 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 solubilizer, a buffer, a preservative, a flavor, a pigment, a sweetener, and the like can be used. The composition for colds and rhinitis of the present invention usually complies with the standard for cold medicine and the standard for oral medicine for rhinitis which are listed in the over-the-counter drug manufacturing guidelines (2000 edition, supervised by the Pharmaceutical Affairs Committee, published by Jiho Co., Ltd.). It is manufactured.

[0012]

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 The following components and amounts were weighed, mixed well, and sieved.
Tablets were produced using a tableting machine (Clean Press Collect 19; manufactured by Kikusui Seisakusho). In addition, one tablet weighs 200 mg
And an 8 mm diameter corner flat punch was used. Emedastine fumarate 2 g Isopropamide iodide 7.5 g Phenylpropanolamine hydrochloride 90 g Anhydrous caffeine 150 g Lactose 148 g Microcrystalline cellulose (Avicel PH201) 150 g Magnesium stearate 2 g

Example 2 The following components and amounts were weighed, mixed well, and sieved.
A tablet was produced according to Example 1. In addition, one tablet weight 200
mg and a punch having an 8 mm-diameter corner plane was used. Ebastine 5 g Belladonna total alkaloid 0.6 g Phenylpropanolamine hydrochloride 100 g Lysozyme chloride 90 g (titer) Anhydrous caffeine 75 g Lactose 160 g Microcrystalline cellulose 167 g Magnesium stearate 2.4 g

Example 3 The following components and amounts were weighed, mixed well, and sieved.
A tablet was produced according to Example 1. In addition, one tablet weight 200
mg and a punch having an 8 mm-diameter corner plane was used. Ramatroban 75 g dl-Methylephedrine hydrochloride 45 g Belladonna extract 60 g Anhydrous caffeine 80 g Tablets 55 g Low-substituted hydroxypropylcellulose 83 g Magnesium stearate 2 g

Example 4 The following components and amounts were weighed, uniformly mixed, and sieved. Based on Example 1, 200 mg tablets were obtained. Bepotastine besilate 20g Methoxyphenamine hydrochloride 150g Roth extract 3 times trituration 180g Dipotassium glycyrrhizinate 200g Anhydrous caffeine 150g Lactose 95g Microcrystalline cellulose 120g Magnesium stearate 5g

Example 5 The following components and amounts were weighed, mixed and pulverized (screen diameter: 1 mm) with a Jariya pulverizer, and 300 mg of the mixed and pulverized product was filled in No. 1 hard capsule to prepare a capsule. The capsules were filled by hand. Ebastine 10 g Datsura extract 0.6 g Phenylpropanolamine hydrochloride 100 g Lysozyme chloride 90 g (titer) Anhydrous caffeine 100 g Calcium hydrogen phosphate 93 g Microcrystalline cellulose 104 g Magnesium stearate 2. 4g

Example 6 A preservative, a sweetener and a flavor are added to an aqueous solution in which a pH adjuster (phosphate buffer) is dissolved, and the solution is completely dissolved. The sucrose fatty acid ester is uniformly dispersed in the solution. Then, after adding and dissolving the other chemicals, purified water was added to make the total amount to 1000 mL, thereby producing the mixture. Emedastine 4 g Phenylephrine hydrochloride 30 g Belladonna extract 60 g Anhydrous caffeine 75 g Sucrose fatty acid ester 15 g Mannitol 15 g Stevia 10 g Ethyl aminobenzoate 5 g Orange flavor 1 g

Test Example 1 [Comparison of shrinkage-inhibiting action on isolated guinea pig ileum] << Test method >> An isolated ileum of a male Hartley guinea pig weighing about 300 g was subjected to the experiment. In the experiment, the effects of emedastine and diphenhydramine hydrochloride and triperinamine as comparative drugs alone and the combined effect with belladonna total alkaloid on ileal acetylcholine contraction were compared by the Magnus method. The application concentration of each drug was emedastine (10 ⁻⁶ g / mL), diphenhydramine hydrochloride (10 ⁻⁶ g / mL), triperinamine (10 ⁻⁶ g / mL), belladonna total alkaloid (1
In 0 ^{-5 g /} mL), the combined effect was treated with dosages administered alone in the same amount in each drug.

<< Test Results >> FIG. 1 shows emedastine (Em
e) shows the effect of acetylcholine on guinea pig ileal contraction when treated with diphenhydramine hydrochloride (DH) or triperinamine (Trl) alone at 10 ⁻⁶ g / mL. Belladonna total alkaloids (10 ⁻⁵ g / m
By the application of L), the contraction of the guinea pig ileum by acetylcholine was significantly suppressed.

FIG. 2 shows belladonna total alkaloids (BA).
And emedastine (Eme), diphenhydramine hydrochloride (DH), triperinamine (Trl),
The acetylcholine contraction of guinea pig ileum was inhibited. No effect was observed in the group treated with diphenhydramine hydrochloride and triperinamine plus belladonna total alkaloids, but in the group treated with emedastine and belladonna total alkaloids, the effect of belladonna total alkaloids on enhancing acetylcholine contraction in guinea pig ileum was suppressed. Was seen.

[0022]

INDUSTRIAL APPLICABILITY The present invention provides a composition for colds and rhinitis which has a remarkable effect on the elimination / reduction of nasal hyperplasia (nasal water) symptoms associated with abnormal secretory glands of the nasal mucosa, among various nasal symptoms. According to the present invention, a remarkably useful drug can be provided for so-called nasal symptoms such as cold syndrome or rhinitis.

[0023]

[Brief description of the drawings]

FIG. 1: 10 ⁻⁶ g of emedastine (Eme), diphenhydramine hydrochloride (DH), triperinamine (Trl)
1 shows the effect of acetylcholine on guinea pig ileal contraction when treated alone / mL.

FIG. 2 shows the inhibitory action of guinea pig ileum on acetylcholine contraction by the combined use of belladonna total alkaloid (BA), emedastine (Eme), diphenhydramine hydrochloride (DH), and triperinamine (Trl).

Continued on the front page (51) Int.Cl. ⁷ Identification FI FI Theme Court II (Reference) A61P 27/16 A61P 27/16 31/16 31/16 (72) Inventor Joji Nakagami 3-chome Takada, Toshima-ku, Tokyo 24-1, Taisho Pharmaceutical Co., Ltd. (72) Katsuyoshi Aikawa, Inventor 3- 24-1, Takada, Toshima-ku, Tokyo (72) Inventor Taisho Pharmaceutical Co., Ltd. No. 1 Taisho Pharmaceutical Co., Ltd. F term (reference) 4C086 AA01 AA02 BC12 BC21 MA02 MA04 NA14 ZA34 ZB33 4C088 AB48 BA40 CA03 MA02 NA14 ZA34 ZB33 4C206 AA02 GA01 MA02 MA04 NA14 ZA34 ZB33

Claims (2)

[Claims] At least one selected from the group consisting of emedastine, ebastine, ramatroban, bepotastine and salts thereof, and at least one selected from the group consisting of belladonna (total) alkaloids, belladonna extract, funnel extract, isopropamide iodide and datura extract. A composition for colds and rhinitis, comprising at least one compound. 2. The composition for colds and rhinitis according to claim 1, wherein nasal secretion is eliminated or reduced.