JPH08208483A - Mequitazine-containing pharmaceutical preparation - Google Patents

Abstract

PURPOSE: To obtain the subject pharmaceutical preparation synergistically excellent in the action of remitting the symptoms of acute rhinitis or allergic rhinitis, etc., and low in side effect such as dipsesis or constipation. CONSTITUTION: This pharmaceutical preparation contains, as active ingredient, a formulation composed of at least one kind of cholinergic blocking agent selected from tropan alkaloids and iodized isopropamide and mequitazine. The amount of the cholinergic blocking agent to be used is 0.03-0.1 pts.wt. per pt.wt. of the mequitazine; when using at least one kind of the cholinergic blocking agent selected from belladonna extract and scopolia extract, the amount of the cholinergic blocking agent is 3-10 pts.wt. per pt.wt. of the mequitazine. The amount of the iodized isopropamide to be used is 0.37-1.88 pts.wt. per pt.wt. of the mequitazine.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a mequitazine-containing preparation having few side effects. More specifically, it has a strong action of relieving symptoms of acute rhinitis, allergic rhinitis, etc., and has immediate effect, and also thirst, constipation, etc. The present invention relates to a mequitazine-containing preparation having few side effects.

[0002]

2. Description of the Related Art Conventionally, antihistamines have been used for the purpose of alleviating symptoms such as acute rhinitis and allergic rhinitis. As this antihistamine agent, chlorpheniramine maleate or the like is generally used, but the antihistamine agent typified by chlorpheniramine maleate has side effects such as drowsiness and weakness, which is a big problem in use. It was. Therefore, mequitazine has been developed and used as an antihistamine.

[0003]

However, mequitazine has a slightly weaker antihistamine action than chlorpheniramine maleate, and its clinical effect is delayed, so that symptoms such as acute rhinitis and allergic rhinitis are alleviated. There was a problem that the action to do was weak.

The present invention has been made in view of the above-mentioned circumstances, and improves meritadine's weak action of alleviating the symptoms of acute rhinitis, allergic rhinitis, etc., and is immediately effective, and moreover, such as dry mouth and constipation. The object is to provide a mequitazine-containing preparation with few side effects.

[0005]

Means and Action for Solving the Problems The present inventors have
As a result of intensive studies to achieve the above-mentioned object, when at least one anticholinergic agent selected from tropane alkaloids and iodoisopropamide is used in combination with mequitazine, both act synergistically to cause acute rhinitis and allergic properties. It has been found that it has a strong effect of relieving symptoms such as rhinitis, has an immediate effect, and has an unexpected and excellent effect of having few side effects.

That is, symptoms such as acute rhinitis and allergic rhinitis are alleviated by the antihistamine action and anticholinergic action of the drug. On the other hand, when the anticholinergic effect becomes excessive, dry mouth,
There is a problem that side effects such as constipation are likely to appear.
Moreover, since mequitazine has a strong anticholinergic effect as compared with other antihistamines, as well as an antihistamine effect,
When an anticholinergic agent was mixed at the same time, the anticholinergic effect became excessive, and side effects such as dry mouth and constipation were likely to occur. However, surprisingly, at least one selected from tropane alkaloids and isopropamide iodide.
When an appropriate amount of various anticholinergic agents is used in combination with mequitazine, the drug effect is extremely high, but the synergistic effect that there are few side effects is expressed, the action to relieve symptoms such as acute rhinitis and allergic rhinitis is strong, and immediate effect, Moreover, the inventors have found that a mequitazine-containing preparation having few side effects such as dry mouth and constipation can be obtained, and that the above-mentioned conventional problems can be effectively solved, and the present invention has been completed.

Accordingly, the present invention provides a mequitazine-containing preparation characterized in that at least one anticholinergic agent selected from tropane alkaloids and isopropamide iodide is used in combination with mequitazine.

The present invention will be described in more detail below. In the mequitazine-containing preparation of the present invention, at least one anticholinergic agent selected from tropane alkaloids and iodoisopropamide as described above is used in combination with mequitazine. Here, the mequitazine used in the present invention includes mequitazine [(quinuclidyl-3-methyl) -10-phenothiazine (Quinuclidedi).
nyl-3-methyl) -10-phenothi
azine)] and salts thereof, etc., and usually 9 to 99% by weight can be added to the formulation.

On the other hand, the anticholinergics used in the present invention are selected from tropane alkaloids and isopropamide iodide. In this case, a large number of tropane alkaloids have been found from nature, centering on plants of the Solanaceae and Coca family, specifically, those containing hyoscyamine, atropine, scopolamine, etc. as active ingredients. Atropa Belladonna (Atr
opera belladonna), belladonna extract, belladonna extract, belladonna (total) alkaloids, datsura extract obtained from plants of the genus Datsura, datsura alkaloids, rotocon obtained from plants of the same genus or other genus plants, chicks obtained from chicks, or Examples include hyoscyamine and salts thereof purified and synthesized from these raw materials, atropine and salts thereof (tropine sulfate), scopolamine and salts thereof (scopolamine hydrobromide), homatropine and salts thereof (homatropin hydrobromide) and the like. The total alkaloid refers to all of the various alkaloids contained in the above drug, and the total amount thereof is expressed as hyoscyamine (C ₁₇ H ₂₃ NO: 289.37).

The compounding amount of the above anticholinergic agent is appropriately selected, but in particular, belladonna (total) alkaloids, datsura alkaloids, datsura extract (as total alkaloids), belladonnacon (as total alkaloids), rotocon (total alkaloids). In the case of hyos (as a total alkaloid), atropine and its salt, scopolamine and its salt, hyoscyamine and its salt, 0.03 to 0.1 parts by weight per 1 part by weight of mequitazine, and more preferably It is 0.05 to 0.1 part by weight. The amount of the belladonna extract and the funnel extract is 3 to 10 parts by weight, more preferably 5 to 10 parts by weight, based on 1 part by weight of mequitazine. The amount of iodoisopropamide added is 0 based on 1 part by weight of mequitazine. 0.37 to 1.88 parts by weight, and more preferably 0.62 to 1.25 parts by weight. If the content of the anticholinergic agent is less than the lower limit of the above range, the action of alleviating symptoms such as acute rhinitis and allergic rhinitis is weak, it is not immediately effective, the dispersibility is poor when formulated, and a uniform formulation May not be able to get. On the other hand, if the amount exceeds the upper limit of the above range, side effects such as dry mouth and constipation may occur.

The mequitazine-containing preparation of the present invention further comprises acetaminophen, lactylphenetidine, and
Aspirin, aspirin aluminum, etenzamid,
Sazapyrine, salicylamide, sodium salicylate,
Isopropylantipyrine, ibuprofen, tranexamic acid, alclofenac, indomethacin, epirisol, tiaramid hydrochloride, tinolidine hydrochloride, ketoprofen, diclofenac sodium, tolmetin sodium, naproxen, fenbufen, aluminum flufenamic acid, mefenamic acid, acemethacin hydrochloride, benzydamine, choline salicylate, Diflunisal, sulpirine, thiaprofenic acid, piroxicam, phenacetin,
Antipyretic and analgesic anti-inflammatory agents such as pranoprofen, isothipendyl hydrochloride, iproheptin hydrochloride, difeterol hydrochloride, diphenylpyraline hydrochloride, diphenhydramine hydrochloride, triprrolidine hydrochloride, triperenamine hydrochloride, tonzylamine hydrochloride, promethazine hydrochloride, metzirazine hydrochloride diphenhydramine salicylate, carbinoxamine diphenyldisulfonate, Alimemazine tartrate, diphenhydramine tannate, diphenylpyraline theoclate, carbinoxamine maleate, chlorpheniramine maleate, chlorpheniramine maleate, promethazine methylenedisalicylate, phenetadine hydrochloride, mebuhydroline napadisylate, difuterol phosphate, and fumaric acid. Antihistamines such as clemastine, phenylpropanolamine hydrochloride, Phenylephrine acid, dl-methylephedrine, 1-methylephedrine, methoxyphenamine hydrochloride, dl-methylephedrine saccharinic acid, trimethoquinol hydrochloride, aloclamide hydrochloride, cloperastine hydrochloride, carbetapentane citrate, tipepidine citrate, dibunato sodium, Dextromethorphan hydrobromide, dextromethorphan phenolphthaline salt, tipepidine hibenzate, cloperastine fendizoate, codeine phosphate, dihydrocodeine phosphate, noscapine hydrochloride, noscapine, potassium guaiacolsulfonate, guaifenesin, potassium cresolsulfonate, Antitussive and expectorant such as dimemorphan phosphate, epradinone hydrochloride or bronchodilator, lysozyme chloride, bromelain, ethylcysteine, hydrochloric acid Chill cysteine,
Serapeptase, bromhexine hydrochloride, sputum solubilizers such as semi-alkaline proteinase, central stimulants such as sodium benzoate caffeine, caffeine, anhydrous caffeine, glycyrrhizic acid and its salts, vitamin B1 and its derivatives, and their salts, vitamin B2 And derivatives thereof and salts thereof, vitamin C and derivatives thereof and salts thereof, hesperidin and derivatives thereof and vitamin agents such as salts thereof, aminoacetic acid, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide , Dihydroxyaluminum / aminoacetic acid salt (aluminum glycinate), aluminum hydroxide gel, dry aluminum hydroxide gel, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide Coprecipitation product of sodium bicarbonate,
Aluminum hydroxide / calcium carbonate / magnesium carbonate co-precipitation product, magnesium hydroxide / potassium aluminum sulfate co-precipitation product, magnesium carbonate, antacids such as magnesium metasilicate magnesium aluminate gel, licorice, kayga, saishin, and show Kyou, Shini, Zenko, Juniper, Maou, Nantenjitsu, Saruhi, Onji, Kyokyo, Chazenshi, Chazensou, Senega, Fritillaria, Fennel, Oubaku, Coptis, Gautu, Chamomile, Keihi, Gentiana, Gourd, Beast, Shajin, Sojutsu, , Chinpi, juniper, ground dragon, chixetsu carrot, carrot, kakkonto, keishito, kososan, saiko keishito, shosaikoto, shoseiryuto, bakumonto, half summer kobokuto, maoto, katsura Properly combine herbal medicines such as hemp each half bath, mao-bushisaishinto and Kampo prescription It is possible.

The mequitazine-containing preparation of the present invention is for alleviation of symptoms caused by acute rhinitis, allergic rhinitis or sinusitis,
Sneezing, stuffy nose, stuffy nose, loose eyes, sore throat,
It is effective for head weight, cold symptoms, acute upper respiratory tract inflammation, asthma, and allergic symptoms.

The mequitazine-containing preparation of the present invention can be orally administered to an adult in a single dose or in divided doses so that the total daily dose of mequitazine and the anticholinergic agent is 1 to 200 mg. This dose can be appropriately increased or decreased depending on the age, body weight and symptoms of the patient.

Furthermore, the mequitazine-containing preparation of the present invention is used in various dosage forms such as tablets, pills, granules, powders, capsules, syrups, dispersants and oral liquids. These preparations can be prepared by a conventional method. As components that can be used for preparing a solid preparation, sucrose granules, sucrose / constarch mixed granules, crystalline cellulose granules, core substances such as lactose / crystalline cellulose mixed granules; lactose, starch, sucrose, Excipients such as mannitol and crystalline cellulose; binders such as hydroxypropylmethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, gelatin, sodium carboxymethylcellulose, gum arabic; carboxymethylcellulose calcium, polyvinylpyrrolidone or crosslinked products thereof, low-substituted hydroxypropylcellulose Disintegrators such as; nonionic surfactants such as sucrose fatty acid esters and polyoxysorbitan fatty acid esters; calcium stearate, magnesium stearate, dimethylpolysiloxane, talc Corn starch, there are lubricants such as polyethylene glycol, hardened oil, a coloring agent, if other required, and sweeteners may be used. If necessary, a coating can be applied, and as a coating agent, ethyl cellulose, Eudragit, hydroxypropylmethyl cellulose phthalate, hydroxypropylmethyl cellulose acetate succinate, methacrylic acid, methyl methacrylate acrylic acid copolymer, cellulose acetate phthalate, polyvinyl There are pyrrolidone, polyethylene glycol, shellac, methyl cellulose, cellulose acetate phthalate and the like, and sugar coating mainly composed of sucrose, gum arabic, calcium carbonate, talc, gelatin and the like can be applied.

The components that can be used in the preparation of liquid formulations include purified water, ethanol, glycerin, sucrose, propylene glycol, polyethylene glycol, polyoxyethylene sorbitan fatty acid ester, aluminum metahydroxide, agar, tragacanth gum, and the like. If necessary, dissolution aids, buffers, preservatives, fragrances, coloring agents,
A flavoring agent or the like may be used, and the compounding amount thereof may be a usual dose.

[0016]

INDUSTRIAL APPLICABILITY The mequitazine-containing preparation of the present invention has a strong action of relieving symptoms such as acute rhinitis and allergic rhinitis,
It has excellent properties that are immediate and have few side effects such as dry mouth and constipation.

[0017]

EXAMPLES The present invention will be specifically described below by showing experimental examples and examples, but the present invention is not limited to the following examples.

Nasal discharge, which is a symptom of rhinitis, occurs by a mechanism similar to salivary secretion caused by cholinergic stimulation. That is, the higher the inhibitory effect on salivary secretion caused by cholinergic stimulation, the higher the effect on alleviating symptoms such as acute rhinitis and allergic rhinitis. However, when saliva secretion is excessively suppressed, side effects such as dry mouth are likely to occur. Therefore, the inhibitory effect on saliva secretion caused by cholinergic stimulation was measured using mice, and the action of the mequitazine-containing preparation to alleviate symptoms such as acute rhinitis and allergic rhinitis was evaluated. Next, side effects such as dry mouth and constipation were evaluated by a sensory test by taking volunteers based on the above experimental results.

[Experimental Example 1] Inhibitory effect on salivary secretion caused by cholinergic stimulation Male ddY mice (body weight: 25 to 30 g) were prepared in groups of 10 and used in the experiment. The test drug was suspended in gum arabic and orally administered at a rate of 0.1 ml / 10 g body weight. As a control, 0.1 ml / 1 of gum arabic suspension only
It was orally administered at a rate of 0 g body weight. 45 minutes after oral administration, anesthesia was performed with Nembutal. Fifteen minutes later, that is, 60 minutes after oral administration, 1.25 mg / kg of carbachol was intraperitoneally administered, and the secretory weight of saliva was measured every minute with a cotton ball for 10 minutes. I asked. Based on the results, the salivary secretion inhibition rate was calculated from the following calculation formula (1), and the 50% effective dose (ED50) was calculated as Litchfield & Litchfield &
Wilcoxon) method. The results are shown in Table 1. In a test in which mequitazine and an anticholinergic agent were administered, the value of ED50 was expressed as the amount of mequitazine + anticholinergic agent (total shown in Table 1). Furthermore, this value was converted into the compounding ratio of each drug. Then, it was also displayed as a value corresponding to mequitazine and an anticholinergic agent.

[0020]

[Equation 1]

[0021]

[Table 1]

Inhibitory effect on salivary secretion of datura alkaloid, belladonnacon (as total alkaloid), rotocon (as total alkaloid), hyos (as total alkaloid), atropine and its salt, scopolamine and its salt, hyoscyamine and its salt, etc. Also had the same results as Belladonna (total) alkaloids.

From the results shown in Table 1, it was confirmed that the salivary secretion inhibitory effect was exhibited by a remarkably small amount of the drug by combining and combining mequitazine or the anticholinergic agent in an appropriate amount as compared with the case of using them alone. In this case, in particular, belladonna (total) alkaloids, datura alkaloids, datura extract (as total alkaloids), belladonnacon (as total alkaloids), rotocon (as total alkaloids), hyos (as total alkaloids), atropine and its salts, scopolamine and its Salt, hyoscyamine and its salts are added in an amount of 0.03 parts by weight or more based on 1 part by weight of mequitazine, and belladonna extract and funnel extract are added in an amount of 3 parts by weight or more based on 1 part by weight of mequitazine. , And isopropamide iodide,
It was found that by adding 0.37 parts by weight or more to 1 part by weight of mequitazine, the inhibitory effect on salivary secretion caused by stimulation with cholinergic agents was synergistically increased.

As a result, it was found that mekitadine can be used in addition to belladonna alkaloids, datura alkaloids, datura extract, belladonnacon, rotcon, hyos, atropine and its salts, scopolamine and its salts, hyoscyamine and its salts, belladonna extract, fungal extract, isopropamide iodide and the like. It was found that the effect of alleviating the symptoms such as acute rhinitis and allergic rhinitis was synergistically enhanced by adding an appropriate amount of at least one anticholinergic agent selected from the following.

[Experimental Example 2] Sensory test by taking volunteers 0.05 to 0.1 parts by weight of belladonna (total) alkaloid was added to 4 to 5 healthy men and women per 1 part by weight of mequitazine as an experimental drug. After oral administration of three kinds of mequitazine-containing agents mixed in 0.15 parts by weight, a sensory test was conducted for side effects according to the evaluation criteria shown in Table 2. The results are shown in Table 3.
Shown in

[0026]

[Table 2]

[0027]

[Table 3]

From the results shown in Table 3, meadazine was added with belladonna (total) alkaloids in an amount of 0.1 per 1 part by weight of mequitazine.
It has been found that by adding more than the weight part, the frequency of complaining of side effects such as dry mouth, which interferes with daily life, increases. In addition, although the results are not shown in the table, similarly, datura alkaloid, datura extract (as total alkaloid), belladonnacon (as total alkaloid),
In the case of rotocon (as total alkaloids), hyos (as total alkaloids), atropine and its salts, scopolamine and its salts, hyoscyamine and its salts, by adding more than 0.1 parts by weight to 1 part by weight of mequitazine, Further, in the case of belladonna extract and funnel extract, by blending more than 10 parts by weight with respect to 1 part by weight of mequitazine, and in the case of iodoisopropamide, by blending more than 1.88 parts by weight with respect to 1 part by weight of mequitazine, It was observed that side effects such as dry mouth, which interferes with daily life, were frequently reported.

From the results of the above Experimental Examples 1 and 2, the mequitazine-containing preparation of the present invention is synergistically excellent in the action of alleviating the symptoms such as acute rhinitis and allergic rhinitis, and has immediate effect, and also has dry mouth and constipation. In order to obtain a mequitazine-containing preparation with few side effects such as
Belladonna (total) alkaloids, Datsura alkaloids,
Datula extract (as total alkaloids), belladonnacon (as total alkaloids), rotocon (as total alkaloids), hyos (as total alkaloids), atropine and its salts, scopolamine and its salts, hyoscyamine and its salts, 1 mequitazine 1 weight 0.03 to 0.1 parts by weight per 1 part by weight, belladonna extract and funnel extract with 3 to 10 parts by weight per 1 part by weight of mequitazine, and iodoisopropamide with 1 part by weight of mequitazine. For 0.37 ~
It has been found effective to incorporate 1.88 parts by weight.

The following are examples in which the mequitazine-containing preparation of the present invention is applied to various dosage forms. In the following examples, the salivary secretion inhibition rate was determined by the same method.

Example 1 Hard Capsule The same ddY mouse as in Experimental Example 1 was used in the experiment. Hard capsules containing the following ingredients were prepared. Remove the contents from the hard capsule, grind in a mortar, and suspend in gum arabic to give 2 mg / kg of mequitazine.
Was orally administered so that 45 minutes after oral administration, anesthesia was performed with Nembutal. 15 minutes later, ie oral administration 6
After 0 minutes, 0.1 mg / kg of carbachol was intraperitoneally administered, and the salivary secretion inhibitory rate was calculated by the same method as in Experimental Example 1. The results are shown in Table 4. Composition Ingredients (in 1 capsule) Blending amount (mg) Mequitazine 2 Belladonna (total) alkaloid 0.1 Phenylpropanolamine hydrochloride 45 Dipotassium glycyrrhizinate 25 Anhydrous caffeine 40 Corn starch 60 Talc 10 White sugar 100 Aquacoat 15 Triethyl citrate 5

Example 2 Hard Capsule A hard capsule containing the following components was prepared. Remove the contents from the hard capsule, mash in a mortar,
Suspended in gum arabic to give mequitazine at 2 mg /
Oral administration was performed so that the dose became kg. The salivary secretion inhibition rate at that time is shown in Table 4. Composition Ingredients (in one capsule) Blending amount (mg) Mequitazine 2 Belladonna (total) alkaloid 0.2 Phenylpropanolamine hydrochloride 45 Dipotassium glycyrrhizinate 25 Anhydrous caffeine 40 Corn starch 60 Talc 9 White sugar 100 Aquacoat 15 Triethyl citrate 5

Example 3 Hard Capsule A hard capsule containing the following components was prepared. Remove the contents from the hard capsule, mash in a mortar,
Suspended in gum arabic to give mequitazine, 2 mg /
Oral administration was performed so that the dose became kg. Table 4 shows the salivary secretion inhibition rate at that time. Composition Ingredients (1 capsule) Blending amount (mg) Mequitazine 2 Belladonna (total) alkaloid 0.06 Phenylpropanolamine hydrochloride 45 Dipotassium glycyrrhizinate 25 Anhydrous caffeine 30 Corn starch 60 Talc 9 White sugar 100 Aquacoat 15 Acetylated monoglyceride 5

Example 4 Tablets Tablets were prepared containing the following ingredients. The tablets were ground in a mortar, suspended in gum arabic and orally administered as mequitazine at 2 mg / kg. Table 4 shows the salivary secretion inhibition rate at that time. Composition Ingredients (in one tablet) Blending amount (mg) Mequitazine 1 Isopropamide iodide 1.25 Phenylpropanolamine hydrochloride 20 Lysozyme chloride 10 Anhydrous caffeine 15 Hydroxypropylcellulose 2 Crystalline cellulose 50 Corn starch 10 Carboxymethylcellulose 20 Magnesium stearate 3

Example 5: Granule A granule containing the following components was prepared. The granules were ground in a mortar, suspended in gum arabic and orally administered as mequitazine at 2 mg / kg. Table 4 shows the salivary secretion inhibition rate at that time. Composition Ingredients (in one package) Blending amount (mg) Mequitazine 2 Datura extract (as total alkaloid) 0.1 Phenylpropanolamine hydrochloride 45 Dipotassium glycyrrhizinate 25 Anhydrous caffeine 40 Corn starch 60 Arabic gum 5

[Example 6] Granules Granules containing the following components were prepared. The granules were ground in a mortar, suspended in gum arabic and orally administered as mequitazine at 2 mg / kg. Table 4 shows the salivary secretion inhibition rate at that time. Composition Ingredients (in one package) Mixing amount (mg) Mequitazine 2 Belladonna extract 20 Phenylpropanolamine hydrochloride 45 Dipotassium glycyrrhizinate 25 Anhydrous caffeine 40 Corn starch 20 Partially pregelatinized starch 30 Hydroxypropyl cellulose 5

Example 7: Tablets Tablets containing the following ingredients were prepared. The tablets were ground in a mortar, suspended in gum arabic and orally administered as mequitazine at 2 mg / kg. Table 4 shows the salivary secretion inhibition rate at that time. Composition Ingredients (in 1 tablet) Blending amount (mg) Mequitazine 2 Belladonnacon (as total alkaloid) 0.15 Phenylpropanolamine hydrochloride 40 Dipotassium glycyrrhizinate 20 Anhydrous caffeine 50 Crystalline cellulose 60 Lactose 10 Magnesium stearate 1

Example 8: Granule A granule containing the following components was prepared. The granules were ground in a mortar, suspended in gum arabic and orally administered as mequitazine at 2 mg / kg. Table 4 shows the salivary secretion inhibition rate at that time. Composition Ingredients (in one package) Blending amount (mg) Mequitazine 2 Rohto extract 14 Phenylpropanolamine hydrochloride 45 Dipotassium glycyrrhizinate 25 Anhydrous caffeine 40 Corn starch 60 Talc 9 Lactose 10 White sugar 80

Example 9: Tablet A tablet containing the following ingredients was prepared. The tablets were ground in a mortar, suspended in gum arabic and orally administered as mequitazine at 2 mg / kg. Table 4 shows the salivary secretion inhibition rate at that time. Composition Ingredients (in 1 tablet) Compounding amount (mg) Mequitazine 1 Belladonna (total) alkaloid 0.05 Ethenzamide 100 Anhydrous caffeine 20 Potassium guaiacol sulfonate 40 Dihydrocodeine phosphate 5 Vitamin C 50 Magnesium stearate 2 Crystalline cellulose 80 Hydroxypropyl cellulose 5

Example 10: Tablet A tablet containing the following ingredients was prepared. The tablets were ground in a mortar, suspended in gum arabic and orally administered as mequitazine at 2 mg / kg. Table 4 shows the salivary secretion inhibition rate at that time. Composition Ingredients (in 1 tablet) Compounding amount (mg) Mequitazine 1 Belladonna (total) alkaloid 0.1 Acetaminophen 100 Dihydrocodeine phosphate 3 dl-Methylephedrine hydrochloride 15 Glycyrrhizic acid 10 Anhydrous caffeine 15 Hydroxypropylcellulose 8 Magnesium stearate 1.5 Crystalline cellulose 70

Example 11: Granule A granule containing the following components was prepared. The granules were ground in a mortar, suspended in gum arabic and orally administered as mequitazine at 2 mg / kg. Table 4 shows the salivary secretion inhibition rate at that time. Composition Ingredients (in one package) Blending amount (mg) Mequitazine 1 Belladonna (total) alkaloid 0.1 Acetaminophen 150 Dextromethorphan hydrobromide 15 dl-Methylephedrine hydrochloride 15 Lysozyme chloride 20 Caffeine 15 Corn starch 60 Hydroxypropyl Cellulose 4 Mannitol 20

[0042]

[Table 4]

From the results of Table 4, in the mequitazine-containing preparation of the present invention, mequitazine 2 mg / kg and anticholinergic agent 0.0
By combining 5 to 20 mg / kg, good results with a salivary secretion inhibition rate of 57.6 to 62.7% were obtained. On the other hand, the drug amount (ED
50) is 41.5 mg when mequitazine is used alone.
/ Kg, 7.9 to 801 when the anticholinergic agent is used alone
mg / kg (Experimental Example 1), the mequitazine-containing preparation of the present invention has a remarkably small drug amount (especially about 1 mg of mequitazine).
/ 20), an excellent saliva secretion inhibitory effect was observed.

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Claims (4)

[Claims] 1. A mequitazine-containing preparation comprising a combination of at least one anticholinergic agent selected from tropane alkaloids and isopropamide iodide in combination with mequitazine. 2. Belladonna (total) alkaloids, datura alkaloids, datura extract (as total alkaloids), belladonnacon (as total alkaloids), rotocon (as total alkaloids), hyos (as total alkaloids), atropine and its compounds as anticholinergics. The mequitazine-containing preparation according to claim 1, wherein 0.03 to 0.1 part by weight of at least one selected from a salt, scopolamine and a salt thereof, hyoscyamine and a salt thereof is mixed with 1 part by weight of mequitazine. 3. The mequitazine-containing preparation according to claim 1, wherein 3 to 10 parts by weight of at least one selected from belladonna extract and funnel extract are mixed as an anticholinergic agent with respect to 1 part by weight of mequitazine. 4. The mequitazine-containing preparation according to claim 1, wherein 0.37 to 1.88 parts by weight of iodoisopropamide as an anticholinergic agent is mixed with 1 part by weight of mequitazine.