JP2003081821A - Medicinal composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a medicinal composition which exhibits remarkably improved antitussive effects against tussive syndromes due to cold syndromes, pollinosis and the like. SOLUTION: This medicinal composition exhibiting remarkably improved antitussive effects against tussive syndromes due to cold syndromes, pollinosis and the like contains (a) one or more selected from the group consisting of acetaminophen and ibuprofen, (b) one selected from the group consisting of belladonna (total) alkaloids, belladonna extract, scopolia extract, isopropamide iodide, and stramonium extract, and (c) one selected from the group consisting of guaifenesin, potassium guaiacolsulfonate, bromhexine hydrochloride, ambroxol hydrochloride, as ingredients.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a pharmaceutical composition to be used as a cold medicine, a cough suppressant or a rhinitis medicine. Specifically, it is a pharmaceutical composition having an improved antitussive effect against coughing symptoms caused by cold syndrome, hay fever and the like.

[0002]

2. Description of the Related Art Conventionally, any component of acetaminophen and ibuprofen and guaifenesin, potassium guaiacolsulfonate, bromhexine hydrochloride,
A variety of pharmaceutical compositions containing any of the components of ambroxol hydrochloride are known, but these are combined with any of the components of belladonna (total) alkaloids, belladonna extract, funnel extract, isopropamide iodide, and datura extract. No known pharmaceutical composition is known. On the other hand, none of the existing drugs have sufficient antitussive effect, and thus there has been a demand for a pharmaceutical composition having a satisfactory effect.

[0003]

Generally, it is known that most of the cold syndromes are caused by viruses, but at present, treatment with antiviral agents is still limited to influenza, and In cold syndrome, symptomatic treatment is mainly used. In particular, coughing symptoms consume a lot of energy because of the sudden movement of many parts of the chest.
The persistent coughing symptom is considered to induce chronicity of the whole cold symptom, and it is an important therapeutic point how quickly various symptoms, especially coughing symptom, are eliminated or reduced.

Under these circumstances, many antitussives for colds which deal with the symptoms of cough are mainly narcotic drugs such as codeines and those mainly having a central respiratory depressant action.
Although this drug has a long-standing track record of effects, it has severe side effects such as drowsiness, hallucinations and constipation in the narcotic component, and thus its usage and dose are strictly limited. In the field of over-the-counter drugs, which are widely used by consumers and intended for self-medication, these drugs were inconvenient and difficult to use. There was a situation where drug development was desired.

[0005]

Means for Solving the Problems As a result of intensive studies aimed at improving the effect of eliminating and reducing cough caused by a cold, the present inventors have found that by combining an antipyretic analgesic, a secretion inhibitor and an expectorant. It was found that the effect was remarkably enhanced, and the present invention was completed.

That is, the present invention provides the active ingredient (a)
One or two selected from the group consisting of acetaminophen and ibuprofen, (b) one selected from the group consisting of belladonna (total) alkaloids, belladonna extract, fungal extract, isopropamide iodide and datura extract, and (c) guaifenesin It is a cough suppressant for colds characterized by containing an antitussive effect remarkably by containing one kind selected from the group consisting of, potassium guaiacol sulfonate, bromhexine hydrochloride and ambroxol hydrochloride.

The belladonna (total) alkaloid is an alkaloid extracted mainly from the roots of belladonna (Atropa belladonna Linne), and the main components are l-hyoscyamine, atropine, scopolamine. , Apoatropin
e) etc. Similarly, the belladonna extract is an extract extracted from the above belladonna. In addition, the funnel extract is an extract extracted from the rhizome and root of the Scopolia japonica Maximowicz or other plants belonging to the same family (Solanaceae). The main components are l-hyoscyamine, atropine, and scopolamine. (Scopolamine) etc. In addition, Datura extract is a product of Datura s
tramonium Linne), Morning glory (Dat)
ura tatula Linne) or a related plant, Solanaceae (Solanacea)
e) is an extract mainly extracted from leaves, the main components of which are l-hyoscyamine and atropin.
e), scopolamine, meteroidin (me
teloidine) and the like.

The antitussive drug for colds of the present invention can be made into a drug which is suitable for other cold symptoms besides coughing symptoms by appropriately blending other drugs in addition to the above components. . These ingredients can be used alone or in combination with each other, and they are usually listed in the Pharmaceutical Manufacturing Guidelines (2000 version, Jiho Co., Ltd.) for cold drug manufacturing (import) approval standards, antitussive and expectorant drug manufacturing (import). ) Blended in accordance with approval standards.

The cough medicine for cold according to the present invention is usually used for adults per day with acetaminophen of 150-150.
0 mg is good, preferably 300-900 mg,
The ibuprofen content is preferably 100 to 1200 mg, more preferably 150 to 600 mg. Further, the belladonna (total) alkaloid is preferably 0.05 to 1 mg, preferably 0.1 to 0.6 mg, and the belladonna extract is 5
-100 mg is preferable, 10-60 mg is preferable, 5-100 mg is preferable for the fungus extract, 10-60 mg is preferable, and iodoisopropamide is 1-1.
0 mg is good, preferably 1.5-7.5 mg,
The Datsura extract is preferably 0.05 to 1 mg, more preferably 0.1 to 0.6 mg. Further, guaifenesin is preferably 50 to 400 mg, and preferably 100 to 300 m.
g is good, potassium guaiacol sulfonate is 45 to 3
50 mg is good, preferably 90-270 mg is good,
Bromhexine hydrochloride preferably has a dose of 2.5 to 20 mg, preferably 5 to 15 mg, and ambroxol hydrochloride has a dose of 7.
5 to 50 mg is preferable, and 15 to 45 mg is preferable. However, this dose can be appropriately increased or decreased depending on the age, body weight, medical condition, and the amount mixed with other components.

The mixing ratios of the components (a), (b) and (c) are as follows: (a):
(B) :( c) = 1: 0.00003 to 1: 0.001
4 to 4, and preferably (a) :( b) :( c) = 1:
0.0001 to 0.5: 0.005 to 2 is preferable.

Further, the cough medicine for cold according to the present invention is a tablet, granule, fine granule, powder, capsule, chewable agent, effervescent agent, drop agent, instant dissolution agent, dry syrup agent, oral solution, inhalation. It can be used as a dosage form preparation such as a drug, a stream agent and the like. These preparations can be prepared by a conventional method. Carriers used to prepare the formulation include lactose, starch, sugar, mannitol,
Excipients such as crystalline cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, gelatin, binders such as PVP, carboxymethylcellulose calcium, disintegrants such as low-substituted hydroxypropylcellulose, magnesium stearate, hydrogenated castor oil, talc, etc. There are lubricants, and if necessary, solubilizing agents, buffers, preservatives, perfumes, dyes, corrigents and the like can be used.

In addition, as the carrier used for the preparation of the oral liquid preparation, sucrose fatty acid esters, polyoxyl stearates, polyoxyethylene polyoxypropylene glycols, polyoxyethylene monofatty acid esters, etc. Agents, synthetic aluminum silicate, magnesium silicate, magnesium carbonate, magnesium oxide, thickeners such as magnesium aluminometasilicate, organic acid-based / inorganic acid-based pH adjusters such as citrate buffer and phosphate buffer In addition to these, solubilizing agents, buffering agents, preservatives, perfumes, sweeteners and the like can be used as required.

[0013]

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 and amounts were weighed and uniformly mixed, and the obtained mixed powder was put into a No. 2 hard capsule to give 200 parts.
Each mg was filled to obtain a capsule. Ibuprofen 200g Datura extract 0.5g Pseudoephedrine hydrochloride 80g Guaifenesin 150g Lactose 250g Microcrystalline cellulose 250g Magnesium stearate 15.5g

Example 2 The following components and amounts were weighed and uniformly mixed, and the resulting mixed powder was tableted by direct compression to a tablet weight of 250 mg to give tablets. Acetaminophen 600 g Belladonna extract 50 g Bromhexine hydrochloride 12 g Lactose 264 g Microcrystalline cellulose 249 g Magnesium stearate 18 g Hardened castor oil 12 g

Example 3 The following components and amounts were weighed and uniformly mixed, and in accordance with Example 2, one tablet weight 30
Tablets were obtained by compressing to 0 mg. Ibuprofen 450 g Isopropamide iodide 7.5 g Chlorpheniramine maleate 6 g Ambroxol hydrochloride 45 g Lysozyme chloride 90 g (potency) lactose 496.5 g Microcrystalline cellulose 488 g Magnesium stearate 20 g Hardened castor oil 20 g

Example 4 The following components and amounts were weighed and uniformly mixed, and in accordance with Example 2, one tablet weight 30
0 mg tablets were obtained.

Ibuprofen 400 g Pseudoephedrine hydrochloride 213 g Belladonna (total) alkaloid 0.6 g Potassium guaiacol sulfonate 250 g Anhydrous caffeine 75 g Vitamin B ₁ nitrate 8 g Vitamin B ₂ 4 g Lactose 300 g Microcrystalline cellulose 295 g Magnesium stearate 20 g Hardened castor oil 17.

(Example 5) The following components were added to distilled water and stirred to homogenize. After that, adjust the pH to 4.3 with a pH adjuster (phosphate buffer), add purified water to bring the total volume to 1000.
It was made into mL. Acetaminophen 600 g dl-Chlorpheniramine maleate 12 g Methylephedrine hydrochloride 45 g Roth extract 45 g Potassium guaiacol sulfonate 150 g Lysozyme chloride 60 g (potency) Anhydrous caffeine 50 g Vitamin C 100 g D-sorbitol 50 g Sodium citrate 5 g Polyoxyethylene curing Castor oil 1g Fragrance slight amount

(Experimental example 1) [Effect of compounded preparation on cough symptom] <Test method> Using a Hartley type guinea pig having a body weight of 300 to 400 g, feed and drinking water were freely ingested in an environment of room temperature 25 ± 2 ° C. After preliminary breeding, it was used for an experiment. Anesthetized guinea pigs were placed in the body plethysmograph. body pl
The ethysmograph consists of two transparent acrylic cylindrical boxes (about 1.2L) for the head and body, and an acrylic neck restrainer covered with two rubber membranes, one above the other.

The method of Kohrogi et al. (J. Clin. Invest. 82,2063
Up to 2068), spray capsaicin 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), presence or absence of cough, strength and frequency of cough reflex were examined. While checking the coughing sound with a microphone, the flow meter (MEP-MEP-
1100, 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.

As the drugs to be compared, the formulations shown in (Table 1) were dissolved in 50 mL of purified water. Each group was tested with 5 animals, and each group was orally administered with 3 mL of the drug 30 minutes before exposure to capsaicin. (The control group was given 3 mL of purified water.)

[0022]

[Table 1]

The results are shown in (Table 2).

[0024]

[Table 2]

It was confirmed that 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 the effect was excellent.

[0026]

INDUSTRIAL APPLICABILITY The present invention was able to provide a drug which has an improved action on cough reaction and is remarkably useful for cold syndrome and the like.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) A61K 31/192 A61K 31/192 35/78 35/78 CR A61P 11/02 A61P 11/02 11/14 11/14 29/00 29/00 43/00 121 43/00 121 (72) Inventor Joji Nakagami 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. (72) Inventor Yasushi Nakagawa O. 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. (72) Inventor Katsuyoshi Aikawa 3-24-1 Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. F-term (reference) 4C088 AB12 AB48 AC05 AC11 AC12 CA03 MA02 NA05 ZA07 ZA08 ZA34 ZA62 ZC75 4C206 AA01 AA02 CA34 DA24 FA31 GA01 GA02 GA22 GA31 JA09 KA01 KA14 MA03 MA04 NA05 ZA07 ZA08 ZA34 ZA62 ZC75

Claims (4)

[Claims] 1. (a) one or two selected from the group consisting of acetaminophen and ibuprofen, (b)
1 selected from the group consisting of belladonna (total) alkaloids, belladonna extract, funnel extract, isopropamide iodide and datura extract, and 1 selected from the group consisting of (c) guaifenesin, potassium guaiacolsulfonate, bromhexine hydrochloride and ambroxol hydrochloride. A pharmaceutical composition comprising a seed. 2. The pharmaceutical composition according to claim 1, which is used as a cold medicine. 3. The pharmaceutical composition according to claim 1, which is used as a cough suppressant. 4. The pharmaceutical composition according to claim 1, which is used as a rhinitis drug.