JPH0680577A - Antitussive - Google Patents

Abstract

PURPOSE:To provide a medicine little in side effect, having significant antitussive effect. CONSTITUTION:The objective antitussive containing, as active ingredient(s), at least one herbal prescription selected from 'shoseiryuto gomakyokansekito', 'keishinieppiichito' and 'eppikahangeto'.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel antitussive agent with few side effects.

[0002]

BACKGROUND OF THE INVENTION Antitussive agents currently in use are classified into narcotic and non-narcotic. Narcotics have strong actions such as antitussive / sedative, analgesic, and diarrhea symptom improvement, but on the other hand, they also have many serious side effects such as arrhythmia, gastrointestinal disorders, and dependence. On the other hand, as non-narcotic ones, synthetic antitussives are known to have fewer side effects than narcotic ones, but central side effects (drowsiness, lightheadedness, malaise) may become a problem, and It is generally said that the action is mild and the effect is clinically insufficient.

Therefore, it has been desired to develop a medicine having few side effects and a remarkable antitussive effect.

[0004]

[Means for Solving the Problems] The inventors of the present invention have conducted extensive studies on various Kampo prescriptions in order to solve the above-mentioned problems, and as a result, they have found that Shoseiryuyu Gomakyo Kansekiyu, Keishiji The inventors have found that Echi-Ichi-to and Etsu-ka-Kanatsu-to have excellent antitussive effect, and completed the present invention.

That is, the present invention is at least selected from Shoseiryu-go Ama-Kan-Kanshi-to, Keishi-Nii-Koshi-Ichi-to, and Koshi-Kaka-Hanatsu-to (collectively referred to as the active ingredients of the present invention). It is an antitussive containing one Kampo prescription as an active ingredient.

[0006] The active ingredients of the present invention, Shoseiryuto Yumakyo Kansekiyu, Keishi-Nii-Koshi-Ichi-to and Koshi-ka-Kanatsu-to, are described in the traditional Chinese herbal formula (Kinbyoyo etc.). Although there are some differences, the compounding range of the crude drug is generally as follows.

Shoseiryu-to Ama-kan-an-kanseki-yu Mao 3.0-6.0 Spicy 2.0-3.0 Shakuyaku 2.0-9.0 Gomiza 1.5-6.0 Ginger 1.5-3.0 Half-summer 3.0-9.0 Licorice 2.0-3.0 Apricot kernel 4.0-6.0 Katsura 2.0-6.0 Gypsum 10.0-30.0 Keishi Futoshikoshi-Ichiyu Keishi 0.75-3.0 Ginger 0.5-3.5 Shakuyaku 0.75-3.0 Daiju 1.0-4.0 Licorice 0.75-3.0 Gypsum 1.0-5.0 Mao 0.75-3.0 Koetsuka-hankayu Mao 4.0-6.0 Daiju 3.0-6.0 Gypsum 8.0-1.0 Licorice 1.0-3.0 Ginger 1.0-6.0 Half-summer 1.0-8.0

[0008] The active ingredient of the present invention is at least one Kampo formula selected from the above-mentioned combination of Shoseiryu-go Amakan-kanseki-to, Keishi-Nii-Koshi-Ichi-to and Koshi-ka-Kanatsu-to. Alternatively, the extract may be used as an active ingredient and combined with a known pharmaceutical carrier to prepare a pharmaceutical preparation.

Examples of the extract include various aqueous solvent extracts, and it is preferable to use the water extract. As a concrete example of adjusting the extract, at least one Kampo prescription selected from Shoseiryu-go Ama-kanseki-to, Keishi-Nii-Koshi-Ichi-to and Koshi-ka-Kanatsu-to with the above composition is used. Examples include a method of extracting with 10 times the amount of hot water and filtering the obtained extract. This extract can be dried if necessary and used as a dry powder.

Specific examples of the active ingredient of the present invention will be shown and described in detail.

Specific Example 1 4.0 g of mahuang, 3.0 g of peony, 3.0 g of ginger, 3.0 g of licorice, and edema 3.
420 in a mixed crude drug (Koseiryuyu Amakan Kansekiyu: 42.0 g) of 0 g, spicy 3.0 g, omizo 3.0 g, half summer 6.0 g, apricot kernel 4.0 g and gypsum 10.0 g
Purified water (g) was added, and the mixture was heated and extracted at 100 ° C for 1 hour. The obtained extract was filtered and then spray-dried to obtain 9.45 g of dry extract powder.

Example 2 2.5 g of cabbage, 2.5 g of peony, 2.5 g of licorice, 2.5 g of mahuang, ginger 1.
A mixed crude drug containing 0 g, 3.0 g of oju and 3.0 g of gypsum (Keishi Nikoshi Eiichito:
170 g of purified water was added to 17.0 g), and the mixture was heated and extracted at 100 ° C for 1 hour. The extract obtained is filtered and then spray-dried 4.
68 g of dry extract powder was obtained.

Specific Example 3 6.0 g of mahuang, 8.0 g of gypsum, 1.0 g of ginger, 3.0 g of oju, 2.0 g of licorice and 5.0 g of half-summer mixed herbal medicine (Etsukaka Hanatsu-to: 25.0 g) in 250 g of purified water Was added, and the mixture was extracted by heating at 100 ° C for 1 hour. The obtained extract was filtered and then spray-dried to obtain 5.91 g of dry extract powder.

Next, the fact that the active ingredient of the present invention has an antitussive effect will be described with reference to experimental examples.

Experimental Example 1 Animal Hartley male guinea pigs (300 to 400 g) were used. Bronchitis patients were prepared by exposing guinea pigs to 200 ppm of sulfurous acid gas for 2 hours and 7 days a day.

Experimental Method 1) Effect on Cough Reflex in Normal Animals (Chemical Stimulation) A healthy guinea pig was placed in a plethysmograph (volume 2355 ml).
Put one animal each and add 20% citric acid aqueous solution or 10 ^-8 M capsaicin aqueous solution to ultrasonic nebulizer (Nihon Kohden, MEP-1100)
Was sprayed for 2 minutes to induce coughing. The cough reflex is recorded on the pen recorder as a cough curve via the respiratory flow meter,
At the same time, he observed a coughing sound with a microphone while observing the symptoms. The reaction was observed during spraying and then for 13 minutes for a total of 15 minutes. The active ingredient of the present invention was dissolved in purified water and orally administered 30 minutes before spraying citric acid or capsaicin. Animals were fasted for 12 hours or longer prior to oral administration.
The effect is the change in the number of cough reflexes for 15 minutes each before and 30 minutes after administration, a group administered with 0.5% carboxymethylcellulose-sodium (CMC-Na) instead of the active ingredient of the present invention.
The comparison was made with that of the (control group). The results for capsaicin-induced cough are shown in Table 1, and the results for citric acid-induced cough are shown in Table 2.

Table 1

Table 2

2) Effect on cough reflex in bronchitis-affected animals (single dose) In the same manner as in the method described above in 1), put one pathological guinea pig in the plethysmograph and spray 20% aqueous citric acid solution. The effect of a single administration of the active ingredient of the present invention on the induced cough was examined. The results are shown in Table 3.

[Table 3]

3) Effect on cough reflex in bronchitis-affected animals (continuous administration) 100 mg / kg of the active ingredient of the present invention and purified water were orally administered daily as a control group, and immediately after that, exposure to sulfurous acid gas was performed.
On the 7th day of exposure, the number of cough reflexes evoked by chemical stimulation (20% citric acid) was measured in the same manner as in 1) above, after standing for 4 hours or more after the end of exposure on that day. The results are shown in Table 4.

Table 4

As is clear from the above results, it was confirmed that the active ingredient of the present invention has a remarkable antitussive effect.
Therefore, Shoseiryuto Gomakyo Kanseki-to, Keishi-Nii-Koshi-Ichi-to and Koshi-ka-Kanatsu-to, which are the active ingredients of the present invention, are useful as antitussives.

Next, the dose and formulation of the active ingredient of the present invention will be described.

The dosage form of the active ingredient of the present invention is not particularly limited and may be appropriately selected and used as needed. Oral preparations such as tablets, capsules, granules, fine granules and powders, injection preparations, Parenteral agents such as suppositories may be mentioned.

In order to exert the intended effect, it depends on the age, body weight and degree of disease of the patient, but usually 3 to 15 g as the weight of the active ingredient of the present invention is divided into several times a day in adults. Seems to be appropriate.

The active ingredient of the present invention includes tablets, capsules,
Oral preparations such as granules are produced by a conventional method using starch, lactose, sucrose, mannitol, carboxymethyl cellulose, corn starch, inorganic salts and the like.

In addition to the above-mentioned excipients, a binder, a disintegrant, a surfactant, a lubricant, a fluidity promoter, a flavoring agent, a coloring agent, a fragrance, etc. may be appropriately used in this type of preparation. You can
Specific examples of each are as shown below.

[Binder] Starch, dextrin, gum arabic powder, gelatin, hydroxypropyl starch, methyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose, crystalline cellulose,
Ethyl cellulose, polyvinylpyrrolidone, macrogol.

[Disintegrant] Starch, hydroxypropyl starch, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, carboxymethyl cellulose, low-substituted hydroxypropyl cellulose.

[Surfactant] sodium lauryl sulfate, soybean lecithin, sucrose fatty acid ester, polysorbate 8
0.

[Lubricant] Talc, waxes, hydrogenated vegetable oil, sucrose fatty acid ester, magnesium stearate, calcium stearate, aluminum stearate, polyethylene glycol.

[Flowability Accelerator] Light anhydrous silicic acid, dried aluminum hydroxide gel, synthetic aluminum silicate, magnesium silicate.

The active ingredient of the present invention can also be administered as a suspension, emulsion, syrup or elixir, and these various dosage forms contain a flavoring agent and a coloring agent. Good.

On the other hand, parenteral preparations are manufactured by a conventional method,
Generally, distilled water for injection, physiological saline, glucose aqueous solution, vegetable oil for injection, sesame oil, peanut oil, soybean oil, corn oil, propylene glycol, polyethylene glycol and the like can be used as the diluent. Further, if necessary, a bactericide, a preservative, and a stabilizer may be added. Further, from the viewpoint of stability, this parenteral preparation may be filled in a vial or the like and then frozen, the water content may be removed by a usual freeze-drying technique, and a liquid preparation may be re-prepared from the freeze-dried product immediately before use. Further, an isotonicity agent, a stabilizer, a preservative, a soothing agent and the like may be added as needed.

Next, the present invention will be described in more detail by showing Examples of the preparation of the active ingredient of the present invention, but the present invention is not limited thereto.

Example 1 Corn starch 21 g Crystalline cellulose 10 g Carboxymethyl cellulose calcium 7 g Light anhydrous silicic acid 1 g Magnesium stearate 1 g Shoseiryuyu Gohmakyo Kansekiyu 160 g Total 200 g According to the above recipe Were evenly mixed and compression-molded with a tableting machine to obtain tablets of 200 mg each. This tablet contains 160 mg of Shoseiryu-go Hamakyo-kanseki-to obtained in Example 1, and 20 to 80 tablets for adults are to be taken in several divided doses per day.

Example 2 Corn starch 29 g Magnesium stearate 2 g Carboxymethyl cellulose calcium 8 g Light anhydrous silicic acid 1 g Keishi Nikokoshi-Ichi-to 160 g obtained in Example 2 Total 200 g After compression molding with a compression molding machine, it was crushed with a crusher and sieved to obtain granules. 1 g of this granule contains 800 mg of Keishi-Nii-Koshigei-to, obtained in Example 2, and 4 to 18 g of the daily dose for an adult is divided into several doses and taken.

Example 3 19 g of corn starch 1 g of light anhydrous silicic acid 180 g of Otsukaka Hanatsuto obtained in Example 3 200 g in total 200 g were uniformly mixed according to the above formulation, and 200 mg was filled in a No. 2 capsule. One capsule of this capsule contains
It contains 20 mg of Otsukahan Hanatsuto obtained in Example 3, and takes 20 to 80 capsules daily for adults in several divided doses.

Claims (1)

[Claims] 1. A cough suppressant containing, as an active ingredient, at least one Kampo prescription selected from Shoseiryuto Yumakyo Kansekiyu, Keishi Nikoshigeiichito and Etsukaka Hanatsuto.