JPH1045576A - Oral medicine for rhinitis - Google Patents

Abstract

(57) [Summary] [Purpose] To provide an oral drug for rhinitis, which is highly effective against various symptoms of rhinitis (in particular, inflammatory symptoms including swelling of nasal mucosa). (A) one or more compounds selected from the group consisting of phenylpropanolamine and its salts, phenylephrine and its salts, methylephedrine and its salts, and methoxyphenamine and its salts; and (b)
An oral drug for rhinitis containing a compound selected from ketotifen fumarate and epinastine hydrochloride.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an internal medicine for rhinitis which has an enhanced or improved effect of removing or alleviating inflammatory symptoms (nasal congestion) of the nasal mucosa among various symptoms of rhinitis.

[0002]

BACKGROUND OF THE INVENTION Rhinitis is an inflammatory disease of the nasal mucosa. The causes are wide-ranging, and sinusitis (pyometra) based on bacterial infection has been attracting attention in the past, but in recent years, the association with allergies has become the main etiology. There are also many types of allergen-causing substances (allergens), such as pollen, house dust, fine particles in exhaust gas, and food components.
Generally, it is thought that allergy is treated by removing allergens, but it is difficult to carry out them in daily life. In addition, desensitization therapy for reducing sensitivity to allergens is also performed, but at present, it is not widely used because the treatment period is very long and frequent hospital visits are involved.

[0003] Under these circumstances, symptomatic treatment is the mainstay. Therefore, how to eliminate or reduce various symptoms of rhinitis as quickly as possible is an important factor both in treatment and in daily life. . In particular, inflammation symptoms such as swelling of the nasal mucosa (nasal obstruction) are
It is also important to treat the disease at an early stage from the viewpoint of prevention of respiratory tract infections such as colds, and this is a very important factor in the field of over-the-counter drugs. It has been difficult to develop a sufficiently effective oral drug for rhinitis.

[0004]

An object of the present invention is to provide various symptoms of rhinitis (particularly inflammatory symptoms including swelling of the nasal mucosa).
To provide an internal medicine for rhinitis that is highly effective against

[0005]

[Means for Solving the Problems] In order to achieve the above-mentioned object, the present inventors selected from the group consisting of phenylpropanolamine and its salts, phenylephrine and its salts, methylephedrine and its salts, and methoxyphenamine and its salts. One or more selected compounds (hereinafter, referred to as
As a result of intensive studies on the combined effects of the combination of (a) component) and various drugs, the active ingredient of the internal medicine for rhinitis was composed of ketotifen fumarate and epinastine hydrochloride in addition to the (a) component. It has been found that the incorporation of one or two compounds selected from the group (hereinafter, sometimes referred to as the component (b)) has a dramatic effect on the elimination or alleviation of symptoms caused by rhinitis. completed.

That is, the present invention relates to (a) one or more compounds selected from the group consisting of phenylpropanolamine and salts thereof, phenylephrine and salts thereof, methylephedrine and salts thereof, and methoxyphenamine and salts thereof. And (b) an oral drug for rhinitis containing one or two compounds selected from the group consisting of ketotifen fumarate and epinastine hydrochloride.

In the present invention, phenylpropanolamine, phenylephrine, methylephedrine (l-form, dl
And methoxyphenamine salts include hydrochloride, nitrate and the like. The component (a) can be used alone or in combination of two or more. The amount is
Phenylpropanolamine and its salts are 10 to 120 mg and phenylephrine and its salts are 3 to 4 per day.
0 mg, methyl ephedrine and its salts are 15 to 125 m
g, methoxyphenamine and its salts are 20 to 175 mg. In addition, ketotifen fumarate is used in an amount of 0.1% per day.
2-4 mg, epinastine hydrochloride 2-25 mg.

In the present invention, in addition to the above active ingredients, if necessary, antihistamines, antiallergic agents, parasympathetic nerve blockers, anti-inflammatory / anti-inflammatory drugs, caffeines, vitamins, crude drugs and the like are used. It can be blended within a range that does not impair the effects of the invention. Examples of antihistamines include isotipendil or a salt thereof, iproheptin or a salt thereof, dipheterol or a salt thereof, diphenylpyraline or a salt thereof, diphenhydramine or a salt thereof, triprolidine or a salt thereof, triperenamine or a salt thereof, promethazine or a salt thereof, and carbinoxamine or Its salts, chlorpheniramine (d form, dl
Body) or salts thereof, astemizole or salts thereof,
Clemastine or a salt thereof, tonsylamine or a salt thereof, dimethindene or a salt thereof, homochlorcyclidine or a salt thereof, and the like, and these can be used alone or in combination of two or more.

As antiallergic drugs, ibudilast,
Oxatomide, mequitazine, amlexanox, azelastine or salts thereof, sodium cromoglycate, repirinast, emedastine or salts thereof, ozagrel or salts thereof, tazanolast, pemirolast or salts thereof, suplatast or salts thereof and the like,
These can be used alone or in combination of two or more. Examples of the parasympathetic blockers include belladonna (total) alkaloids, isopropamide iodide, funnel extract, and datura extract, which can be used alone or in combination of two or more kinds. Examples of the anti-inflammatory enzyme drug / anti-inflammatory drug include lysozyme chloride, bromelain, serrapeptase, semi-alkaline proteinase, pronase, tranexamic acid, glycyrrhizinic acid, and related substances. These may be used alone or in combination of two or more. it can.

[0010] Caffeine includes caffeine and anhydrous caffeine. Examples of vitamins include vitamin B ₁ or a derivative thereof or salts thereof, vitamin B ₂ or a derivative thereof or salts thereof, vitamin C.
And these can be used alone or in combination of two or more. For herbal medicine, half summer, spicy, cabbage,
Ginger, licorice, saiko, cinnamon (branch), (purple) soybean leaf, mahuang, peony, schizandra, yellow melon, river cucumber, ground yellow, yellow ream, Chinese bellflower, continuous jade, spicy red, clove, eucalyptus, eucalyptus, lavender And herbal powders such as Bakumondo and extracts thereof, and these can be used alone or in combination of two or more.

[0011] These components can be used alone or as a mixture with one another. The internal medicine for rhinitis of the present invention,
Tablets, capsules, granules, fine granules, powders, chewables, effervescent agents, using conventional carriers, in the usual manner.
It can be prepared into oral dosage forms such as drops, dissolving agents in the mouth, dry syrups, and oral liquids.

The carrier used in the preparation of the solid formulation includes 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, fragrances, pigments, flavoring agents and the like can be used.

[0013] In addition, the carrier used in the preparation of the preparation in the oral liquid preparation includes surfactants such as sucrose fatty acid esters, polyoxyl stearate, polyoxyethylene polyoxypropylene glycols and polyoxyethylene mono fatty acid esters. , Synthetic aluminum silicate,
Thickeners such as magnesium silicate, magnesium carbonate, magnesium oxide, magnesium aluminometasilicate,
There are organic acid-based and inorganic acid-based pH adjusters such as citrate buffer, phosphate buffer, etc.
Buffering agents, preservatives, fragrances, dyes, corrigents, sweeteners and the like can be used.

[0014]

EXAMPLES Hereinafter, the present invention will be described in more detail by way of examples and test examples, but the present invention is not limited to these examples. (Example 1) Phenylpropanolamine hydrochloride 80 g Ketotifen fumarate 2 g Anhydrous caffeine 300 g Lactose 100 g Microcrystalline cellulose 60 g Magnesium stearate 48 g Hardened castor oil 10 g The above components and amounts were weighed and uniformly mixed, and then obtained. The mixed powder was tableted by a direct compression method so that one tablet weighed 100 mg to obtain a tablet.

(Example 2) Phenylpropanolamine hydrochloride 100 g Epinastine hydrochloride 20 g Belladonna (total) alkaloid 0.4 g Lysozyme chloride 90 g (potency) anhydrous caffeine 300 g Lactose 100 g Microcrystalline cellulose 80 g Magnesium stearate 52 g Hardened castor oil 7. 6 g According to the same manner as in Example 1, 100 mg of tablets was obtained after weighing and uniformly mixing the above components and amounts.

Example 3 Phenylephrine hydrochloride 30 g Ketotifen fumarate 2 g Belladonna alkaloid 0.4 g Dipotassium glycyrrhizinate 200 g Lidocaine hydrochloride 500 g Anhydrous caffeine 300 g Lactose 200 g Microcrystalline cellulose 140 g Magnesium stearate 100 g Hardened castor oil 27. The above components and amounts were weighed and uniformly mixed, and then 200 mg tablets were obtained according to Example 1.

Example 4 l-Methylephedrine hydrochloride 110 g Ketotifen fumarate 2 g Isopropamide iodide 7.5 g Lysozyme chloride 90 g (potency) Anhydrous caffeine 300 g Cycin 3 g (active drug equivalent amount) Shini 3 g (active drug equivalent amount) ) Lactose 100 g Microcrystalline cellulose 70 g Magnesium stearate 60 g Hardened castor oil 8.5 g The above components and amounts were weighed and uniformly mixed, and then 100 mg tablets were obtained according to Example 1.

(Test Example) [Effect of Combination Preparation on Rhinitis Symptoms] According to the prescriptions (daily dose) shown in Tables 1 and 2 below, capsules are manufactured by a conventional method, and patients with chief complaint of allergic rhinitis symptoms are obtained. They were taken as subjects and their effects were compared.

[0019]

[Table 1]

[0020]

[Table 2]

<Test Method> Of 106 adult men and women complaining of nasal congestion due to allergic rhinitis, 70 patients who agreed to conduct the test were divided into 10 subjects each of groups A to G. , The drug of the above Table 1 or Table 2 was taken twice a day, respectively, and after 1 day, 2 days, and 3 days, the degree of inflammation symptoms (nasal obstruction) of the nasal mucosa was classified into 5 levels (significant improvement; complete nose). Closed, improved; slight slight nasal congestion remains, slightly improved; nasal obstruction from the original state, unchanged; unchanged from the original state, worse; nasal obstruction stronger than the original state) Judgment was made, the transition was observed, and comparison was made among the five groups. No concomitant drug was used in all cases. <Test results> Results show improvement rate of nasal congestion symptoms (slight improvement or more)
As shown in Table 3.

[0022]

[Table 3]

The degree of improvement of the nasal congestion symptom is superior in the group A than in the other groups, and the oral administration of rhinitis combined with the active ingredient of the present invention shows an excellent effect in removing and improving rhinitis symptoms. Proven.

 ───────────────────────────────────────────────────の Continuing on the front page (72) Inventor Kenji Tsunoda 3-24-1, Takada, Toshima-ku, Tokyo Inside Taisho Yaku Co., Ltd.

Claims (1)

[Claims] 1. A compound of (a) phenylpropanolamine and a salt thereof, phenylephrine and a salt thereof, methylephedrine and a salt thereof, methoxyphenamine and a salt thereof, and (b). An oral medicine for rhinitis containing one or two compounds selected from the group consisting of ketotifen fumarate and epinastine hydrochloride.