JP2002332229A - Common cold composition - Google Patents

Abstract

(57) [Problem] To provide a composition for colds with an improved effect on nasal congestion (nasal congestion) caused by cold syndrome or rhinitis. SOLUTION: The composition for colds containing (a) at least one of ketotifen, epinastine, emedastine, carbinoxamine, mequitazine and chlorpheniramine, and (b) pseudoephedrine.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a composition for colds. More specifically, the present invention relates to a composition for colds containing a drug having an antiallergic effect and a sympathomimetics and effective for reducing or eliminating rhinitis mainly caused by colds.

[0002]

2. Description of the Related Art A number of cold remedies containing a drug having an antiallergic effect have been developed so far, but the effect of suppressing or reducing nasal congestion, which is a vasodilatory lesion of the nasal mucosa, is still not sufficient. However, further enhancement of the effect has been desired as long as the safety is not adversely affected.

[0003]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a composition for colds which is effective for reducing or eliminating inflammatory symptoms (such as nasal congestion) of the nasal mucosa.

[0004]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, by mixing pseudoephedrine, which is a sympathomimetic, with various drugs having antiallergic activity, the nasal mucosa is improved. The present inventors have found that the present invention exerts an excellent action of reducing or eliminating inflammatory symptoms (such as nasal congestion), thereby completing the present invention.

That is, the present invention relates to (a) ketotifen, epinastine, emedastine, carbinoxamine,
At least one of mequitazine and chlorpheniramine,
And (b) a composition for colds, which contains pseudoephedrine.

[0006] Ketotifen which is the component (a) of the present invention,
Epinastine, emedastine, carbinoxamine, mequitazine and chlorpheniramine (d-form and dl-form)
Drugs having an antiallergic effect, which may be salts. And particularly preferred are ketotifen and epinastine.

The compounding amount of the component (a) in the present invention may be a normal dose as an antiallergic drug. For example, a daily dosage for an adult is 0.5 to 3 mg for ketotifen and 5 for epinastine. ２５25 mg, 1-5 mg for emedastine, 3.5 for carbinoxamine
-20 mg, 1-6 mg for mequitazine and 1.5-15 mg for chlorpheniramine.

[0008] Pseudoephedrine, component (b) of the present invention, is a sympathomimetic. Here, the sympathetic stimulant refers to a drug that exhibits the same effect as when stimulating an adrenergic nerve, and is also called an adrenergic agonist. Pseudoephedrine may be a salt.

The compounding amount of pseudoephedrine as the component (b) of the present invention is 0.1 to 1 part by mass of the component (a).
The amount is 4 parts by mass or more, and 5 to 20 parts by mass is preferable from the viewpoint that the effect of reducing or eliminating nasal congestion is remarkably exhibited. 0.
If the amount is less than 4 parts by mass, the effect of reducing or eliminating nasal congestion is not sufficient, and if it exceeds 20 parts by mass, there is no remarkable effect on the effect of reducing or eliminating nasal obstruction.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION The anti-cold composition of the present invention is provided, for example, in the form of a solid preparation such as a tablet or powder, and is orally administered to an adult once or several times a day. be able to. This dose can be appropriately increased or decreased depending on age, body weight, symptoms and the like. The cold-sensitive composition of the present invention has a tablet, capsule, granule, fine granule, powder, chewable, foaming agent, dropping agent, dissolving agent in the mouth,
It can be used as a preparation for oral administration such as a dry syrup, an oral solution and the like. These preparations can be prepared by a conventional method.

Carriers used in the preparation of solid preparations include excipients such as lactose, starch, sugar, mannitol, 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.

[0012] Carriers used for the preparation of preparations in oral liquid preparations include 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 metasilicate aluminate,
There are organic acid-based and inorganic acid-based pH adjusters such as citrate buffer, phosphate buffer, etc.
Buffers, preservatives, flavors, dyes, sweeteners and the like can be used.

The composition for colds of the present invention may optionally contain other active ingredients in addition to the above components as long as the effects of the present invention are not impaired.

[0014]

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 thereto. In addition, a collect 19 type manufactured by Kikusui Seisakusho was used as a tableting machine for producing tablets, and an 8 mm-diameter corner plane was used as a tableting punch.

Example 1 The following components were weighed and thoroughly mixed, and a tablet weighing 200 mg was produced. Mequitazine 4 g pseudoephedrine hydrochloride 60 g lysozyme chloride 100 g (titer) anhydrous caffeine 75 g lactose 303 g microcrystalline cellulose (Avicel PH201) 306 g magnesium stearate 7 g

Example 2 The following components were weighed and thoroughly mixed to prepare a tablet weighing 200 mg per tablet. Ketotifen fumarate 2 g pseudoephedrine hydrochloride 60 g Lysozyme chloride 100 g (titer) Anhydrous caffeine 75 g Lactose 303 g Microcrystalline cellulose (Avicel PH201) 306 g Magnesium stearate 9 g

Example 3 The following components were weighed and thoroughly mixed, and a tablet weighing 200 mg was produced. Epinastine hydrochloride 10 g pseudoephedrine hydrochloride 30 g Belladonna total alkaloid 0.4 g Lysozyme chloride 90 g (titer) Anhydrous caffeine 75 g Lactose 228.6 g Microcrystalline cellulose 226 g Magnesium stearate 20 g

Example 4 The following components were weighed and thoroughly mixed to prepare a tablet weighing 200 mg per tablet. Carbinoxamine maleate 7.5 g pseudoephedrine hydrochloride 90 g isopropamide iodide 5 g lysozyme chloride 90 g (titer) anhydrous caffeine 75 g lactose 198.6 g microcrystalline cellulose 193.9 g magnesium stearate 20 g

Example 5 The following components were weighed and thoroughly mixed, and a tablet weighing 200 mg was produced. Emedastine fumarate 2 g Pseudoephedrine hydrochloride 60 g Belladonna total alkaloid 0.3 g Bromelain 50,000 units Tablets 60 g Low substituted hydroxypropylcellulose 27.7 g Magnesium stearate 12 g

Example 6 The following components were weighed and thoroughly mixed, and a tablet weighing 150 mg was produced. dl-Chlorpheniramine maleate 12 g pseudoephedrine hydrochloride 90 g Isopropamide iodide 7.5 g Dipotassium glycyrrhizinate (200 g as glycyrrhizic acid) Caffeine anhydride 75 g Lactose 135.5 g Microcrystalline cellulose 135 g Magnesium stearate 24 g Hardened castor oil

Example 7 A pH adjuster (phosphate buffer), a preservative (ethyl aminobenzoate), a sweetener (mannitol, stevia), and a flavor (orange flavor) are dissolved in purified water. The sugar fatty acid ester was dispersed uniformly. After adding and dissolving ketotifen fumarate and other chemicals to this solution, purified water was added to adjust the total amount to 5%.
000 mL to prepare an oral solution. Ketotifen fumarate 2 g Phenylephrine hydrochloride 30 g Belladonna total alkaloids 0.3 g Anhydrous caffeine 75 g Sucrose fatty acid ester 15 g Mannitol 15 g Stevia 10 g Ethyl aminobenzoate 5 g Orange flavor 0.8 g

(Test Example) [Comparison of nasal respiratory resistance in guinea pigs] Male guinea pigs were intraperitoneally administered 10 μg / kg of ovalbumin and 5 mg / kg of aluminum hydroxide gel three times every two weeks. Thereafter, for local sensitization, ovalbumin (3 mg / mL) was exposed once a day for 3 minutes with a nebulizer, and this was continued for 4 weeks to prepare an active sensitization model guinea pig.

Ovalbumin was again administered intranasally, and the nasal respiratory resistance after 3 hours was measured. Immediately thereafter, an aqueous solution of a test drug or a control drug listed in Table 1 was administered. Thereafter, the nasal respiratory resistance was measured 30 minutes later. The resistance value of nasal breathing can be indirectly evaluated as indicating the degree of nasal obstruction, and it is estimated that the greater the resistance value, the greater the degree of nasal obstruction. The nasal respiratory resistance of guinea pigs was measured using the body plethysmogram for small animals by the oscillation method ("Japanese Otolaryngology", Japanese Otolaryngology Society 95, 1190-1197, 1992). Two groups (A and B groups), three control drugs (C to E groups), and a control group (F group) were used for each group, 5 animals.

An average of 5 nasal respiratory resistance values immediately before administration of the test drug aqueous solution, the control drug aqueous solution, and the control (purified water) was set to 100, and 30 minutes after each administration of the test drug aqueous solution and the control drug aqueous solution. The average value of the nasal respiratory resistance of each group is shown in the lower column of Table 1.

[0025]

[Table 1]

<< Test Results >> The nasal respiration resistance values in Table 1 are as follows.
The combination prescription group (AB group) was significantly smaller than the plain group (CE group) and the control group (F group), indicating that the combination prescription improved the nasal congestion effect.

[0027]

EFFECTS OF THE INVENTION The composition for colds of the present invention is effective for reducing or eliminating nasal congestion due to inflammation of the nasal mucosa. ), It has become possible to provide useful drugs.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 31/551 A61K 31/551 A61P 11/02 A61P 11/02 (72) Inventor Joji Nakagami Tokyo 3-24-1, Takada, Toshima-ku Taisho Pharmaceutical Co., Ltd. (72) The inventor Katsuyoshi Aikawa 3-24-1, Takada, Toshima-ku, Tokyo Inside Taisho Seiyaku Co., Ltd. (72) Inventor Yasushi Nakagawa Toshima, Tokyo 3-24-1, Takada-ku Taisho Seiyaku Co., Ltd. F-term (reference) 4C086 AA02 BC17 BC21 BC38 BC54 BC89 GA16 MA01 MA02 MA03 MA04 NA05 ZA34 4C206 AA02 FA10 KA01 MA01 MA02 MA03 MA04 MA12 MA14 ZA34

Claims (1)

[Claims] 1. A cold-sensitive composition comprising (a) at least one of ketotifen, epinastine, emedastine, carbinoxamine, mequitazine and chlorpheniramine, and (b) pseudoephedrine.