JP2002348251A - Pharmaceutical composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a pharmaceutical composition of which the effects to cough symptoms caused by cold is enforced. SOLUTION: The pharmaceutical composition is characterized by formulated with agents for solubilizing the airway mucus, such as acetylcysteine, carbocysteine or salts thereof, and the airway vasodilator, such as trimethoquinol, phenylpropanolamine, methoxyphenamine, methylephedrine, pseudoephedrine or salts thereof.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a pharmaceutical composition characterized by eliminating or reducing cough symptoms.

[0002]

2. Description of the Related Art The treatment of colds is mainly symptomatic treatments aimed at improving individual cold symptoms. In particular, cough symptoms that mainly appear during the late to late stages of a cold sickness are rapid exercises of many parts of the chest, so they consume a lot of energy and prolong the overall cold symptoms based on a decrease in physical strength and resistance. It is thought to cause.

[0003] In order to suppress such cough symptoms, central antitussives such as codeines that act on the cough center to suppress cough, and antitussives such as noscapine that suppress cough by suppressing reflex excitement of the cough center are used. I have.

[0004] Acetylcysteine and carbocysteine are known to promote sputum excretion, and trimethokinol, phenylpropanolamine, methoxyphenamine, methylephedrine and pseudoephedrine have a relaxing effect on bronchial smooth muscle, It is known to suppress respiratory excitement.

[0005] However, there is no known composition in which an airway mucolytic agent such as acetylcysteine and carbocysteine is combined with a bronchodilator such as trimethokinol, phenylpropanolamine, methoxyphenamine, methylephedrine and pseudoephedrine.

[0006]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a pharmaceutical composition which has an excellent effect in eliminating or alleviating coughing symptoms such as a cold.

[0007]

Means for Solving the Problems The present inventors have conducted intensive studies for the above purpose and as a result, by combining an airway mucolytic agent and a bronchodilator as active ingredients, it is possible to eliminate cough symptoms during colds and the like. It has been found that there is a dramatic effect on the reduction, and the present invention has been completed. That is,
The present invention is a pharmaceutical composition comprising an airway mucolytic agent and a bronchodilator, which eliminates or reduces cough symptoms.

[0008] The airway mucolytic agent is preferably acetylcysteine, carbocysteine or a salt thereof.

The bronchodilator is preferably trimethoquinol, phenylpropanolamine, methoxyphenamine, methylephedrine, pseudoephedrine or a salt thereof. In addition, pseudoephedrine (pseudoephedrine) may also be called pseudoephedrine, and those having the same three-dimensional structural formula indicate all regardless of the name.

In the present invention, the salt means a pharmaceutically acceptable salt, for example, hydrochloride, nitrate, sulfate, sulfonate, phosphate, oxalate, maleate, fumarate, and the like. Inorganic acid salts and organic acid salts such as acid salts and hydrobromide salts are exemplified.

The compounding amount of the pharmaceutical composition of the present invention is preferably 50 to 800 mg of acetylcysteine or a salt thereof, and 300 to 1500 mg of carbocysteine or a salt thereof per day for an adult. The amount of trimethoquinol or its salt is preferably 1 to 6 mg, the amount of phenylpropanolamine or its salt is preferably 15 to 90 mg, and the amount of methoxyphenamine or its salt is 25 to 150 mg.
mg is preferred, and methylephedrine or a salt thereof is 1 mg.
2.5 to 75 mg is preferred, and pseudoephedrine or a salt thereof is preferably 36 to 240 mg.

As shown in the test examples described below, administration of acetylcysteine, carbocysteine or a salt thereof alone does not have an effect on coughing symptoms, but it does not show any effect on cough symptoms. However, trimethoquinol, phenylpropanolamine, methoxyphenamine, By combining methylephedrine, pseudoephedrine, or any of these salts, the number of cough reactions can be significantly reduced.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION The pharmaceutical composition of the present invention can usually be orally administered to an adult once or several times a day. This dose can be appropriately increased or decreased depending on the age, weight, and medical condition. The pharmaceutical composition of the present invention,
Tablets, capsules, granules, fine granules, powders,
It is used as a preparation for oral administration such as a chewable preparation, a foaming preparation, a drop preparation, a dissolving agent in the mouth, a dry syrup preparation, and an oral liquid preparation. These preparations can be prepared by a conventional method.

In the case of solid preparations, the carriers used in the preparation of preparations include excipients such as lactose, starch, sugar, mannitol, crystalline cellulose, binders such as hydroxypropylcellulose, hydroxypropylmethylcellulose, gelatin, PVP, and carboxy. There are disintegrants such as methylcellulose calcium and low-substituted hydroxypropylcellulose, lubricating agents such as magnesium stearate, hydrogenated castor oil, and talc.In addition, if necessary, dissolution aids, buffers, preservatives, fragrances, and dyes And flavoring agents can be used.

[0015] In the oral liquid preparation, the carrier used for the preparation of the preparation includes 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 solubilizing agent, a buffer, a preservative, a flavor, a pigment, a sweetener, and the like can be used.

The pharmaceutical composition of the present invention may be prepared in accordance with the cold drug standard, antitussive expectorant standard, etc. listed in the Pharmaceutical Manufacturing Guideline (2000 edition, supervised by the Pharmaceutical Affairs Committee, published by Jiho Co., Ltd.). Can be compounded.

[0017]

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 were weighed and uniformly mixed, and the resulting mixed powder was subjected to a direct compression method to obtain tablets weighing 200 mg per tablet.
Ibuprofen 600g carbocisteine 600g phosphate dihydrocodeine 24g fumarate emedastine 1g phenylpropanolamine hydrochloride 60g of anhydrous caffeine 75g Vitamin _{B 1} nitrate 8g vitamin _B 2 4g Lactose 205g Microcrystalline cellulose 200g Magnesium stearate 15g hardened castor oil 8g

Example 2 The following components were weighed and uniformly mixed, and a tablet of 200 mg was obtained according to Example 1. Acetaminophen 900 g Noscapine 48 g Dihydrocodeine phosphate 24 g Chlorpheniramine maleate 10 g Trimethokinol 4 g Acetylcysteine 400 g Lysozyme chloride 90 g (titer) Lactose 150 g Microcrystalline cellulose 152 g Magnesium stearate 10 g Hardened castor oil 10 g

Example 3 The following components were weighed and uniformly mixed, and then 100 mg tablets were obtained according to Example 1. Ibuprofen 300 g Carbinoxamine maleate 12 g Dihydrocodeine phosphate 24 g Acetylcysteine 500 g Pseudoephedrine hydrochloride 120 g Dipotassium glycyrrhizinate 80 g Lactose 100 g Low-substituted hydroxypropylcellulose 90 g Magnesium stearate 16 g Hardened castor oil 8 g

Example 4 A preservative, a sweetening agent, and a flavor are added to an aqueous solution in which a pH adjuster (phosphate buffer) is dissolved, and the solution is completely dissolved. After adding and dissolving ammonophen and other chemicals, purified water was added to make the total volume to 120 L, thereby producing the product. Acetaminophen 600g phosphate dihydrocodeine 24g maleic carbinoxamine 12 g dl-methylephedrine hydrochloride ephedrine 60g carbocisteine 750g anhydrous caffeine 75g Vitamin _{B 1} nitrate 8g vitamin _B 2 4g sucrose fatty acid ester 15g Mannitol 15g stevia 10g ethyl benzoate 5g Grapefruit flavor 0.8g

Experimental Example 1 [Effects of Combination Formulation on Cough Symptoms] Hartley male guinea pigs weighing 300 to 350 g were allowed to freely ingest feed and drinking water in an environment at room temperature of 24 ± 1 ° C., and were preliminarily reared for the experiment. Provided.

A non-anesthetized guinea pig is subjected to body plethysmograp
put in h. The body plethysmograph is an acrylic neck restrainer covered with two transparent acrylic cylindrical boxes (about 1.2 L) for the head and body and two rubber films on the upper and lower sides.
It is composed of

The method of Kohrogi et al. (J. Clin. Invest. 82, 2063)
According to 22068), capsaicin is sprayed from the upper part of the entire surface of the container with an ultrasonic nebulizer (TUR-3200, Nihon Kohden) for 2 minutes (2.2 mL / min), and the presence or absence of cough and the intensity and frequency of cough reflex are examined. Was. The coughing sound was confirmed with a microphone, and the change in the internal pressure of the sealed body box was recorded on a pen recorder via a flow meter (MEP-1100, Nihon Kohden). The evaluation was made based on the presence or absence of suppression of the number of 1-minute cough reactions that occurred. The room temperature was set at 25 ° C.

As a comparison drug, a formulation shown in Table 1 dissolved in 50 mL of purified water was used. Test with 5 animals per group,
In each group, 3 mL of the drug was orally administered 30 minutes before exposure to capsaicin. (The control group received 3 mL of purified water.)

[0026]

[Table 1]

Table 2 shows the results of the number of cough reactions and the inhibition rate from the control group.

The degree of suppression of the cough reaction was greater in the combination prescription group of the groups A and B than in the control group of the groups C to F, which proved to be superior.

[0029]

[Table 2]

[0030]

Industrial Applicability The present invention is a composition having a dramatic effect on the elimination and alleviation of cough symptoms since the antitussive effect due to a cold or the like is enhanced. Significantly useful drugs can be provided for the symptoms.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme court ゛ (Reference) A61P 11/08 A61P 11/08 11/12 11/12 (72) Inventor Joji Nakagami Toshima-ku, Tokyo 3-24-1, Takada Taisho Pharmaceutical Co., Ltd. (72) Inventor Katsuyoshi Aikawa 3-24-1, Takada, Toshima-ku, Tokyo Intra-Chemical Pharmaceutical Co., Ltd. 3-Chome 24-1-1 Taisho Seiyaku Co., Ltd. F-term (reference) 4C084 AA02 AA03 AA20 BA44 CA59 MA02 NA05 ZA612 ZA622 ZA632 4C086 AA01 AA02 BC30 MA02 MA04 MA52 NA05 ZA61 ZA62 ZA63 4C206 AA01 AA02 FA10 FA11 MA57 NA05 ZA61 ZA62 ZA63

Claims (3)

[Claims] (1) A pharmaceutical composition comprising an airway mucolytic agent and a bronchodilator. 2. The airway mucolytic agent is acetylcysteine,
The pharmaceutical composition according to claim 1, which is carbocysteine or a salt thereof. 3. The pharmaceutical composition according to claim 1, wherein the bronchodilator is at least one selected from the group consisting of trimethoquinol, phenylpropanolamine, methoxyphenamine, methylephedrine, pseudoephedrine and salts thereof.