JP2001261561A - Drug for ameliorating nasal obstruction - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a drug for the therapy and amelioration of nasal obstruction which can eliminate or relieve the symptom of nasal obstruction due to the inflammation of the nasal mucous membrane between/among various symptoms of rhinitis e.g. when having a common cold. SOLUTION: This drug for the therapy and amelioration of nasal obstruction is prepared by formulating (a) etodolac with (b) at least one kind selected from the group consisting of mequitazine, ketotifen, epinastine, chlorpheniramine, carbinoxamine and their salts.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a therapeutic and ameliorating agent for nasal congestion having an enhanced effect on nasal congestion in chronic rhinitis symptoms caused by cold and allergic rhinitis.

[0002]

2. Description of the Related Art Various types of rhinitis compositions used for rhinitis and allergic rhinitis associated with cold have been known, but all of them have sufficient effects on the inflammatory symptoms of the nasal mucosa caused by colds and the like. Could not be obtained.

[0003] Nasal congestion is one of the symptoms of rhinitis caused by cold, which is one of the viral respiratory infections, and allergic diseases caused by certain antigen sensitization. For the treatment of the common cold,
The development of a drug having an antiviral effect to suppress the infection and proliferation of the virus is desired as a causative therapy, but at the current state of the art, there is no situation in which an effective drug is still being developed, and the aim is to improve individual cold symptoms. Symptomatic treatment is central to cold treatment. The symptomatic treatment for colds is mainly fever relief by the antipyretic analgesic component and analgesia at the onset of pain symptoms.An anti-inflammatory drug such as etodolac has not been used for colds, or even if used Used in the drug. However, since the common cold is accompanied by various symptoms at the same time as the morbidity, the treatment of a wide variety of symptoms is planned at an early stage, the frequency of drug use is reduced, and the occurrence of side effects is reduced. There has been a demand for the development of a compounding agent with reduced effects and enhanced effects, and the point was how to formulate a formulation that achieves such purpose.

On the other hand, as a treatment for nasal congestion itself, a conventional nasal congestion improving agent mainly comprises an antihistamine drug and, in addition, a sympathomimetic for the purpose of removing nasal congestion. Further, there has been no compound containing an anti-inflammatory drug such as etodolac for the purpose of removing inflammation of the respiratory mucosa. Especially in daily life, rhinitis due to colds and allergies, especially nasal congestion, may lead to respiratory failure, distracting concentration on things, and causing unexpected events. In addition, in the case of the common cold, the direct uptake of fresh air into the lungs by breathing through the mouth leads to new viral and bacterial infections, leading to the disadvantage of prolonged symptoms. From the above, it is possible to effectively eliminate nasal congestion from chronic nasal congestion, and to enable treatment with drugs that can be taken for chronic symptoms over a long period of time. It is an important point.

[0005]

SUMMARY OF THE INVENTION The present invention has been made in view of the above-mentioned prior art, and has as its object the elimination of nasal congestion caused by inflammation of the nasal mucosa among various symptoms of rhinitis such as cold. It is an object of the present invention to provide a nasal congestion treatment / amelioration drug capable of reducing the nose.

[0006]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies for the above purpose, and as a result, by combining a specific nonsteroidal anti-inflammatory drug, an antiallergic drug and an antihistamine drug as active ingredients, The inventors have found that the present invention has a dramatic effect on removing or reducing nasal congestion, which is an inflammatory symptom of the nasal mucosa, and completed the present invention.

That is, the present invention provides (a) etodolac,
(B) a pharmaceutical composition comprising at least one selected from the group consisting of mequitazine, ketotifen, epinastine, chlorpheniramine, carbinoxamine, and salts thereof, for treating or improving nasal congestion associated with rhinitis; provide. According to a preferred embodiment of the present invention, there is provided a therapeutic / ameliorating agent for nasal congestion used for rhinitis associated with cold.
According to a preferred embodiment of the present invention, there is provided a therapeutic or ameliorating agent for nasal congestion used for allergic rhinitis.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The agent for treating or improving nasal congestion according to the present invention comprises a combination of etodolac and at least one selected from the group consisting of mequitazine, ketotifen, epinastine, chlorpheniramine, carbinoxamine and salts thereof. It is a pharmaceutical composition. The rhinitis that causes nasal congestion to which the nasal congestion treatment / ameliorating agent of the present invention is applied is not particularly limited, and includes rhinitis associated with cold, allergic rhinitis, acute rhinitis, chronic rhinitis (simple chronic rhinitis, Hypertrophic rhinitis, atrophic rhinitis), drug-induced rhinitis, specialty rhinitis and the like.
It is particularly preferred that it is applied to allergic rhinitis. Etodolac used in the nasal congestion treatment / ameliorating drug of the present invention is a known anti-inflammatory drug, and mequitazine, ketotifen, epinastine, chlorpheniramine, carbinoxamine and salts thereof are known anti-allergic drugs and antihistamine drugs. And readily available to those skilled in the art.

In the present invention, the salts refer to pharmaceutically acceptable salts of inorganic and organic acids and the like.
Nitrate, sulfate, phosphate, oxalate, maleate, fumarate, hydrobromide and the like can be mentioned.

The drug for treating or improving nasal congestion of the present invention can be usually orally administered to an adult once or several times a day. This dose can be appropriately adjusted depending on the age, weight, and medical condition. The usual compounding amount is, for example, preferably 100 mg to 600 mg of etodolac per day for each adult, 2 to 12 mg of mequitazine is preferable, 0.5 to 3 mg of ketotifen or a salt thereof is preferable, and epinastine (the 5-20 mg is preferable, and chlorpheniramine or its salt is preferably 2-15 mg,
Carbinoxamine or a salt thereof is preferably 5 to 20 mg. The mixing ratio of etodolac and antiallergic or antihistamine is 0.0005 to 1 part by weight of etodolac or its salts.
Preferably it is 0.2 parts by weight.

The drug for treating and improving nasal congestion according to the present invention is in the form of tablets, capsules, granules, fine granules, powders, chewables, effervescent agents, drops, dissolving agents in the mouth, dry syrups, oral liquids, etc. Can be used as a preparation for oral administration. These preparations can be prepared by a conventional method. In solid preparations, lactose, starch, sugar, mannitol, excipients such as crystalline cellulose, hydroxypropyl cellulose,
Hydroxypropyl methylcellulose, gelatin, PV
Binders such as P, carboxymethylcellulose calcium, disintegrants such as low-substituted hydroxypropylcellulose, magnesium stearate, hydrogenated castor oil, lubricating agents such as talc, and the like. Buffers, preservatives, flavors, dyes, flavoring agents, and the like can be used.

[0012] In the oral liquid preparation, as a carrier used for preparation of the preparation, surface active agents such as sucrose fatty acid ester, polyoxyl stearate, polyoxyethylene polyoxypropylene glycol, polyoxyethylene mono fatty acid ester and the like are used. 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 solubilizing agent, a buffer, a preservative, a flavor, a pigment, a sweetener, and the like can be used.

[0013] In addition to the above components, the pharmaceutical composition of the present invention may further contain other nonsteroidal anti-inflammatory drugs, anti-inflammatory enzymes, bronchodilators, central nervous stimulants, antitussives, expectorants,
At least one drug selected from other antihistamines or anticholinergics, vitamins, antacids, crude drugs and the like may be appropriately compounded. These components can be used alone or as a mixture of two or more, and are usually compounded in accordance with the cold medicine standard and the like described in the Pharmaceutical Manufacturing Guidelines (1995 edition, Pharmaceutical Times). .

[0014]

The present invention will be described in more detail with reference to examples and test examples, but the present invention is not limited to the following examples. Example 1 Each of the following components was weighed and mixed uniformly, and then the obtained mixed powder was tableted by a direct compression method so that one tablet weighed 300 mg to obtain tablets.

[0015]

Example 2 After weighing and uniformly mixing the following components, a tablet weighing 310 mg per tablet was obtained in accordance with Example 1.

[0017]

Example 3 The following components were weighed and uniformly mixed. According to Example 1, a tablet weighing 200 mg per tablet was obtained.

Etodolac 400 g Carbinoxamine maleate 12 g Phenylpropanolamine hydrochloride 60 g Lysozyme chloride 90 g Anhydrous caffeine 75 g Lactose 100 g Low-substituted hydroxypropylcellulose 50 g Magnesium stearate 15 g

Example 4 A preservative, a sweetener and a flavor are added to an aqueous solution (phosphate buffer) in which a pH adjuster is dissolved using the following components, and the mixture is completely dissolved. Sucrose fatty acid ester is added to the solution. After uniformly dispersing, etodolac and other chemicals were added and dissolved, and purified water was added to make the total volume 1000 ml to obtain a liquid preparation.

Etodolac 400 g Chlorpheniramine maleate 12 g Phenylpropanolamine hydrochloride 60 g Anhydrous caffeine 75 g Vitamin B1 nitrate 8 g Sucrose fatty acid ester 15 g Preservative (sodium benzoate) Appropriate amount pH adjuster Appropriate amount Sweetener (sucrose) Appropriate Amount Fragrance Fine amount

<< Test Example >> Egg albumin 10 μg / kg and aluminum hydroxide gel 5 m were added to Hartley male guinea pigs.
After intraperitoneal administration of g / kg three times every two weeks, for the local sensitization, nasal administration of ovalbumin (3 mg / 3 ml) for 3 minutes daily for 4 weeks using a nebulizer, and an active sensitization model guinea pig Was prepared. Nasal ovalbumin again, 3
After a lapse of time, the nasal respiratory resistance was measured. Immediately thereafter, an aqueous solution of the test drug or the control drug shown in Table 1 was administered at the dose shown in Table 1. Then, the nasal respiratory resistance 30 minutes later was measured. The nasal respiratory resistance of the guinea pig was measured by the oscillation method using a small animal body plethysmogram. The test drug group and the control drug group were each performed with 7 animals per group. The results are shown in FIG. The results shown in FIG. 1 are graphs comparing the relative values of the nasal respiratory resistance 30 minutes after the administration when the value of the nasal respiratory resistance immediately before the administration of the test drug aqueous solution or the control aqueous solution was set to 100. is there. The degree of nasal obstruction can be measured by measuring the resistance value of nasal respiration, and it is considered that the nasal obstruction degree is higher as the resistance value is higher.

[Table 1]

As shown in FIG. 1, the nasal respiratory resistance was lower in the combination prescription group than in the plain group, and it was proved that the combination prescription showed a better nasal congestion improving effect.

EFFECTS OF THE INVENTION The therapeutic or ameliorating agent for nasal congestion according to the present invention has an enhanced or improved anti-inflammatory effect on chronic inflammation of the nasal mucosa, and has a dramatic effect on the reduction or elimination of rhinitis symptoms. The present invention can provide a drug which is a composition and is extremely useful for nasal congestion associated with rhinitis, particularly nasal congestion associated with rhinitis due to cold, or nasal congestion associated with allergic rhinitis.

[Brief description of the drawings]

FIG. 1 is a graph showing test results showing the nasal congestion improving effect of the nasal congestion treatment / ameliorating agent of the present invention.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 31/12 A61P 31/12 37/08 37/08 (72) Inventor Susumu Kotomo Takada, Toshima-ku, Tokyo 3-Chome 24-1-1 Taisho Yaku Co., Ltd. F-term (reference) 4C086 AA01 AA02 BC21 CB09 CC04 GA03 GA12 MA02 MA04 MA59 NA06 ZA34 ZB11 ZB13

Claims (3)

[Claims] 1. A method for reducing nasal congestion associated with rhinitis, comprising (a) etodolac and (b) at least one member selected from the group consisting of mequitazine, ketotifen, epinastine, chlorpheniramine, carbinoxamine and salts thereof. Treatment / improvement drug. 2. The therapeutic or ameliorating agent for nasal congestion according to claim 1, wherein the rhinitis is rhinitis associated with cold. 3. The method according to claim 1, wherein the rhinitis is allergic rhinitis.
The therapeutic or ameliorating agent for nasal congestion according to 1.