JP2003104903A - Antitussive composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an antitussive composition having an reinforced antitussive activity against coughing symptoms caused by cold syndromes, etc., and having less adverse effects. SOLUTION: This antitussive composition contains (a) at least 1 kind of acetaminophen and ibuprofen, (b) at least 1 kind of belladonna extract, scopolia essence and datura essence and (c) at least 1 kind of codeine, dihydrocodeine, dextromethoruphan, fominoben and noscapine, and the cold medicine is obtained by using the composition.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a pharmaceutical composition used as a cough suppressant, a cold remedy and the like. More specifically, it relates to a composition having an enhanced antitussive action against coughing symptoms caused by cold syndrome and the like.

[0002]

BACKGROUND ART Generally, it is known that most of the cold syndromes are caused by viruses, but at present, treatment with antiviral agents is limited to influenza, and in the common cold syndromes, symptomatic treatment is required. Is the center. And coughing symptoms consume a lot of energy because of the rapid movement of many parts of the chest, and it is thought that prolonged coughing symptoms induce chronicity of all cold symptoms,
How to alleviate and eliminate coughing symptoms is the point of treatment. In such a situation, as a cough remedy for colds that corresponds to a cough symptom, narcotic drugs such as codeines and drugs mainly having a central respiratory depressant action are widely used.

However, although these drugs have a long track record of their effects, they have various side effects such as drowsiness, hallucinations, constipation, etc. in the narcotic component, so that the usage and dose are severely restricted. Is imposed.

Therefore, in the field of over-the-counter drugs for the purpose of self-medication, it is easy to handle,
It has been urgently desired to develop a highly convenient drug that exhibits a sufficient effect even at a low dose.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide an antitussive composition which is effective against coughing symptoms caused by cold syndrome and has few side effects.

[0006]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have blended a certain component having an antipyretic and analgesic action, a component having a secretion suppressing action and a component having an expectorant action. It was found that the drug rapidly reduces and eliminates the antitussive symptom caused by the cold syndrome, and the side effect is not accompanied at that time, and the present invention has been completed.

That is, the present invention provides: (a) at least one of acetaminophen and ibuprofen, (b) at least one of belladonna extract, funnel extract and datsura extract, and (c) codeine, dihydrocodeine, dextromethorphan, An antitussive composition comprising at least one of hominoben and noscapine. Alternatively, it is a cold medicine or the like using the composition.

The (a) component acetaminophen and ibuprofen of the present invention are drugs having an antipyretic and analgesic action. These components (a) may be used alone or in combination of two.

The component (b) of the present invention, the belladonna extract, the funnel extract and the datura extract, are drugs having a secretion-suppressing action. Not only one of these components (b) is used, but two or more of them are used. You may use in combination.

Here, the belladonna extract is an extract or the like extracted from belladonna (Atropa belladonna Linne), and the belladonna total alkaloids and the like mainly extracted from the root correspond to this. Its main ingredients are l-hyoscyamine and atropin.
e), scopolamine, apoatropine, etc.

[0011] In addition, the funnel extract is a lotus root (Sc
opolia japonica Maximowicz), an extract extracted from rhizomes and roots of the other solanaceae (Solanaceae),
The main components are l-hyoscyamine, atropine, scopolamine and the like.

[0012] Further, the Datsura extract is an extract mainly extracted from the leaves of the white-billed Datura stramonium Linne, Datura tatula Linne, or the same genus plant Solanaceae, and the main component is l. − Hyoscyamine (l-hyoscy
amine), atropine, scopolamine (sco
polamine) and meteloidine.

The component (c) of the present invention, codeine, dihydrocodeine, dextromethorphan, hominoben and noscapine are drugs having an expectorant action, and they may be salts. As the salt, hydrochloride, sulfate,
Examples thereof include inorganic acid salts and organic acid salts such as nitrates, phosphates, hydrobromides, citrates, and phenolphthaline salts.
Not only one of these (c) components is used, but 2
You may use it in combination of 2 or more types.

[0014]

BEST MODE FOR CARRYING OUT THE INVENTION In addition to components (a) to (c) of the composition for anesthesia of the present invention, suitable additives may be blended to provide a cough suppressant, a cold remedy, etc. It is also possible to provide other active ingredients as appropriate and provide them as a general cold remedies and the like effective for symptoms other than cough symptoms.

These active ingredients can be used alone or in combination with each other, and they are usually used in the pharmaceutical manufacturing guidelines (200
It is mixed according to the cold drug manufacturing (import) approval standards, antitussive expectorant drug manufacturing (import) approval standards, etc. listed in the 0-year edition, Jiho Co., Ltd.

The dose of the component (a) of the present invention is 150 to 1500 mg for acetaminophen per day for an adult.
And is preferably 300 to 900 mg. For ibuprofen it is 100-1200 mg, 150-600 m
g is preferred.

The dose of the component (b) of the present invention is 0.05 to 1 m per day of adult belladonna total alkaloids.
g, preferably 0.1 to 0.6 mg. And in the extract, it is 5 to 100 mg, preferably 10 to 60 mg. It is 5-100mg for the funnel extract, 1
0-60 mg is preferred. Datsura extract is 0.05 ~
It is 1 mg, preferably 0.1 to 0.6 mg.

The dose of the component (c) of the present invention is 5 to 80 mg of codeine per day for an adult, and 10 to 60
mg preferred. 2.5-40 mg for dihydrocodeine
And is preferably 5 to 30 mg. The amount of dextromethorphan is 5 to 80 mg, preferably 10 to 60 mg. Hominoben is 10-200 mg, 20-1
60 mg is preferred. Noscapine is 5-80 mg, preferably 10-60 mg.

However, the dose of each of the above components can be appropriately increased or decreased depending on the age, body weight, medical condition, and the amount blended with other components.

The compounding ratio of each component in the antitussive composition of the present invention is 0.00003 to 1 part by mass for the component (b) and 0. 0 for the component (c) with respect to 1 part by mass of the component (a). 0
03-2 parts by mass, and in the component (b) 0.0001-
0.5 parts by mass is preferable, and the component (c) is 0.005-
1.1 parts by mass is preferred.

The antitussive composition of the present invention comprises tablets, granules, fine granules, powders, capsules, chewable agents, effervescent agents, drops, instant solubilizers, dry syrups, oral liquids, inhalants and stream agents. And the like.

These formulations can be prepared by a conventional method. Carriers used for preparing solid preparations include excipients such as lactose, starch, sugar, mannitol and crystalline cellulose, binders such as hydroxypropylcellulose, hydroxypropylmethylcellulose, gelatin and polyvinylpyrrolidone (PVP), carboxymethylcellulose calcium. , Low-substituted hydroxypropyl cellulose and other disintegrants, magnesium stearate, hydrogenated castor oil, lubricants such as talc, and other solubilizers, buffers, preservatives, fragrances, pigments, and flavors as needed. Agents and the like.

Further, as a carrier used for the preparation of the oral solution, a surfactant such as sucrose fatty acid ester, polyoxyl stearate, polyoxyethylene polyoxypropylene glycol, polyoxyethylene monofatty acid ester, or synthetic Thickeners such as aluminum silicate, magnesium silicate, magnesium carbonate, magnesium oxide and magnesium aluminometasilicate, pH adjusting agents such as citrate buffer solution and phosphate buffer solution, solubilizing agents, buffer agents, preservatives , Flavoring agents, sweeteners and the like.

[0024]

EXAMPLES The present invention will be described in more detail with reference to examples and test examples.

(Example 1) Ibuprofen 250 g Datsura extract 0.5 g Pseudoephedrine hydrochloride 80 g Dextromethorphan hydrobromide 60 g Lactose 270 g Microcrystalline cellulose 270 g Magnesium stearate 15.5 g The above components were weighed and mixed evenly. No. 2 hard capsules were filled with 200 mg each of the obtained mixed powders to obtain capsules.

Example 2 Acetaminophen 550 g Belladonna extract 50 g Hominoben hydrochloride 120 g Lactose 227 g Microcrystalline cellulose 220 g Magnesium stearate 20 g Hardened castor oil 13 g The above-mentioned components were weighed and uniformly mixed, and then the resulting mixed powder was obtained. Tablets were obtained by direct compression into tablets each weighing 250 mg.

Example 3 Ibuprofen 450 g Belladonna extract 60 g d-Chlorpheniramine maleate 6 g Noscapine hydrochloride 60 g Lysozyme chloride 90 g (potency) Lactose 469 g Microcrystalline cellulose 450 g Magnesium stearate 20 g Hardened castor oil 15 g Each of the above components After weighing and mixing uniformly, according to Example 2, tablets each weighing 300 mg were obtained.

Example 4 Ibuprofen 400 g Pseudoephedrine Hydrochloride 213 g Belladonna Total Alkaloid 0.5 g Codeine Phosphate 60 g Noscapine Hydrochloride 60 g Anhydrous Caffeine 70 g Vitamin B ₁ Nitrate 8 g Vitamin B ₂ 4 g Lactose 240 g Microcrystalline Cellulose 230.3 g Magnesium Magnesium Stearate 20.2 g hydrogenated castor oil 17 g The above components were weighed and uniformly mixed, and according to Example 2, tablets each weighing 300 mg were obtained.

(Example 5) Acetaminophen 600 g dl-Chlorpheniramine maleate 12 g Methylephedrine hydrochloride 45 g Roth extract 45 g Dihydrocodeine phosphate 30 g Noscapine hydrochloride 45 g Anhydrous caffeine 50 g Vitamin C 100 g D-sorbitol 50 g Sodium citrate 5 g Oxyethylene hydrogenated castor oil 1 g Perfume Trace amount purified water Appropriate amount The above components were weighed, added to purified water and dissolved by stirring.
After that, the pH was adjusted to 4.0 with a pH adjuster (phosphate buffer), and purified water was added to make the total amount 1000 mL to prepare an internal solution.

(Test Example 1) [Effect of compounded preparation on cough symptom] Using a Hartley type guinea pig having a body weight of 300 to 400 g, the feed and the drinking water were preliminarily taken under the environment of room temperature 25 ± 2 ° C. After breeding, it was used for an experiment. An unanesthetized guinea pig is treated with a body plethmograph (body pleth
ysmograph). The body plethysmograph consists of two transparent acrylic cylindrical boxes (box; approximately 1.2L) for the head and body, and an acrylic neck restrainer covered with two rubber membranes on the top and bottom.
r).

The method of Kohrogi et al. (J. Clin. Invest. 82,2063
-2068), capsaicin (ca
psaicin) was sprayed with an ultrasonic nebulizer (TUR-3200, Nihon Kohden) for 2 minutes (2.2 mL / min), and the presence or absence of a cough, the intensity and frequency of the cough reflex were examined. While checking the coughing sound with a microphone, the change in the internal pressure of the closed body box is measured with a flow meter (MEP-110).
0, Nihon Kohden) and recorded on a pen recorder.
The presence or absence of suppression of the number of cough reactions that occurred per minute was evaluated as an index. The room temperature was set to 25 ° C.

In the test, a drug prepared by dissolving the prescription components shown in Table 1 in 50 mL of purified water was used. Tested with 5 animals per group,
Each group was orally administered with 3 mL of the drug 30 minutes before exposure to capsaicin. At that time, 3 mL of purified water was added to the control group.
Was given. The results are shown in Table 1.

[0033]

[Table 1] Prescription list of study drug (in 50 mL, unit m
g)

[Table 2] Test Results [Control group for cough frequency (H
Group))

The degree of the inhibitory effect of the Hartley male guinea pigs on the cough reaction was higher in the group A than in the other groups, and it was confirmed that the drug of the present invention has an excellent antitussive effect. Moreover, no particular side effects were observed.

[0035]

INDUSTRIAL APPLICABILITY According to the present invention, it becomes possible to provide an antitussive composition which is improved in the action against cough reaction and which is remarkably useful for cold syndrome and the like, and a pharmaceutical to which the composition is applied.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 31/485 A61K 31/485 31/5375 31/5375 A61P 11/14 A61P 11/14 43/00 121 43 / 00 121 (72) Inventor Joji Nakagami 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. (72) Inventor Katsuyoshi Aikawa 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical In-house (72) Inventor Yasushi Nakagawa 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. F-term (reference) 4C086 AA01 AA02 BC73 CB22 CB23 MA03 MA04 MA17 MA35 MA37 MA52 NA06 NA14 ZA07 ZA08 ZA62 4C088 AB12 AB48 AC05 AC11 AC13 MA17 MA35 MA37 MA52 NA06 NA14 ZA07 ZA08 ZA62 4C206 AA01 AA02 DB22 GA31 MA03 MA04 MA37 MA55 MA57 MA72 NA06 NA14 ZA07 ZA08 ZA62

Claims (2)

[Claims] 1. An antitussive composition comprising the following components (a), (b) and (c): (A) at least one of acetaminophen and ibuprofen (b) at least one of belladonna extract, funnel extract and datura extract (c) at least one of codeine, dihydrocodeine, dextromethorphan, hominoben and noscapine 2. The antitussive composition according to claim 1, which is a cold medicine.