JP2000344682A - Cough suppressant - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a cough suppressant having improved antitussive effect on tussive symptorns by flu syndrome, etc. SOLUTION: This cough suppressant comprises (A) an antitussive and (B) naproxen, ketoprofen, diclofenac sodium or isopropylantipyrine. The antitussive is a codeine such as dehydrocodeine, dextromethorphan, etc., a codeine-related substance, a xanthine-related substance such as a xanthine-related material such as theophylline, aminophylline, diprophylline, proxyphylline, etc., cloperastine, tipepidine, pentoxyverine or alloclamide.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a cough medicine having an improved antitussive effect against cough symptoms caused by cold syndrome and the like.

[0002]

2. Description of the Related Art Among the various symptoms of colds, cough symptoms are:
It is caused by the cough reflex and involves rapid exercise of the chest-related parts, which consumes a lot of energy, and it is thought that continuing cough symptoms may lead to prolongation of the general cold symptoms. Therefore, how to eliminate or alleviate cough symptoms is an important therapeutic point for rapid recovery.

[0003] Under such circumstances, cough suppressants for cough symptoms include, for one thing, the central respiratory depression effect of codeine or its analogs, and the effects of these drugs have been proven for many years. However, many of them are narcotic and have side effects such as addiction, somnolence and hallucinations. The other is due to a bronchial muscle relaxing action typified by xanthine analogs, but these drugs also have side effects such as habit, hyperpnea, insomnia, and frequent urination.
Therefore, the use of these drugs has strict use restrictions on the usage and dosage, and has been inconvenient, especially in the area of self-medication intended for widespread use by consumers. Conventionally, various antitussives containing an antitussive have been known, but the antitussive effect was insufficient due to the above-mentioned side effects.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to provide a cough suppressant having an improved antitussive effect against cough symptoms such as a cold syndrome.

[0005]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, the antitussive effect has been dramatically improved by adding naproxen, ketoprofen, diclofenac sodium or isopropylantipyrine to an antitussive. The inventors have found that the present invention is improved and completed the present invention. That is, the present invention is a cough medicine containing (A) an antitussive and (B) naproxen, ketoprofen, diclofenac sodium or isopropylantipyrine.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION An antitussive in the present invention is used as a medicament and is codeine or a salt thereof (for example, phosphate), dihydrocodeine or a salt thereof (for example, phosphate), dextromethorphan or Salt thereof (eg, hydrobromide), theophylline, aminophylline, diprofylline, proxyphylline, cloperastine or a salt thereof (eg, hydrochloride), tipepidine or a salt thereof (eg, citrate), pentoxiverine or a salt thereof (E.g., citrate), or allocramide or a salt thereof (e.g., hydrochloride), and any one of these can be used. Further, the present invention may contain components having an antitussive action other than the above.

In the present invention, the component which enhances the antitussive effect by being combined with (A) an antitussive is (B) naproxen, ketoprofen, diclofenac sodium or isopropylantipyrine. These are antipyretic analgesics
It is known as an anti-inflammatory drug, and any one of these can be used. In the present invention, a component having an antipyretic analgesic action / anti-inflammatory action other than the above may be included.

A feature of the present invention resides in that the coughing effect is enhanced by adding (B) naproxen, ketoprofen, diclofenac sodium or isopropylantipyrine to (A) an antitussive, which results from the antitussive. This has the advantage that the occurrence of side effects can be reduced.

If necessary, expectorants, antihistamine (antiallergic) drugs, bronchodilators, anti-inflammatory (anti-inflammatory)
Enzyme drugs, anticholinergics, drowsiness drugs, vitamins, crude drugs,
An antacid or the like may be appropriately compounded to prepare a drug for other cold symptoms other than cough symptoms.

[0010] The cough medicine of the present invention is usually used for adults.
300-1500 mg as an active ingredient per day can be taken orally in one or several divided doses. This dose can be appropriately adjusted according to age, weight, and medical condition.

The mixing ratio of the component (B) to the (A) antitussive can be selected in a wide range depending on the type and dosage of the antitussive, and (B) the component (B) per 1 part by weight of the antitussive. In the case of naproxen, ketoprofen, diclofenac sodium, the amount is preferably 0.01 to 300 parts by weight, preferably 0.05 to 120, more preferably 0.75 to 100.
Parts by weight, and when the component (B) is isopropylantipyrine, the amount is preferably 0.03 to 180 parts by weight, more preferably 0.1 to 60 parts by weight, and even more preferably 0.2 to 50 parts by weight. If the compounding ratio is out of this range, the antitussive effect may not be improved.

The cough medicine of the present invention includes, for example, tablets, granules,
It can be used as a dosage form such as fine granules, powders, capsules, chewables, foaming agents, drops, instant dissolving agents in the mouth, dry syrups, oral liquids, inhalants, and streams.

These preparations can be prepared by a conventional method and are not particularly limited. Excipients that can be used in the preparation of solid preparations include excipients, binders, disintegrants, surfactants, antioxidants, lubricants, coating agents,
In addition, flavors, pigments, flavoring agents, and the like can be used as needed.

[0014] Additives that can be used in the preparation of a liquid medicine for internal use include a surfactant, a thickener, and a pH adjuster. In addition, if necessary, a solubilizing agent, a preservative, a sweetener, a flavor, Dyes, flavoring agents and the like can be used.

For other forms of preparations, additives and the like usually used for these preparations can be used.

[0016]

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 Dihydrocodeine phosphate 30 mg, naproxen 300
mg was dissolved in purified water, the pH was adjusted to 4.2 with citric acid and sodium citrate, and purified water was added to adjust the total volume to 50 mL.

Examples 2 to 24 Components and amounts shown in Tables 1 to 6 were weighed and prepared according to Example 1.

Example 25 The following components and amounts were weighed and uniformly mixed, and then 200 mg of the obtained mixed powder was filled in a No. 2 hard capsule.

Naproxen 300 g Dihydrocodeine phosphate 24 g Noscapine 48 g Chlorpheniramine maleate 12 g Methoxyphenamine hydrochloride 250 g Bromhexine hydrochloride 12 g Lactose 250 g Microcrystalline cellulose 186 g Magnesium stearate 14 g Example 26 The following components and amounts were weighed and mixed uniformly. After that, the obtained mixed powder was tableted by a direct compression method so that the weight of one tablet became 250 mg.

Ketoprofen 100 g Epinastine hydrochloride 20 g Dextromethorphan 24 g Noscapine 48 g Ambroxol hydrochloride 45 g Lysozyme chloride 90 g (titer) Lactose 340 g Microcrystalline cellulose 300 g Magnesium stearate 18 g Hardened castor oil 15 g Example 27 The following components and amounts After weighing and mixing uniformly, tableting was performed so that the weight per tablet was 300 mg according to Example 26.

Diclofenac sodium 75 g Ketotifen fumarate 2 g Theophylline 450 g Noscapine 48 g Trimethoxinol hydrochloride 6 g Ambroxol hydrochloride 45 g Lysozyme chloride 60 g (titer) Lactose 400 g Microcrystalline cellulose 375 g Magnesium stearate 20 g Hardened castor oil Example 19 g of the following: After weighing and uniformly mixing the components and amounts, the tablets were compressed to a tablet weight of 300 mg according to Example 26.

[0023] Ketotifen isopropyl antipyrine 150g Fumaric acid 2g diprophylline 325g noscapine 48g ambroxol hydrochloride 45g hydrochloride methylcysteine 300g hydrochloride trimetoquinol Nord 6g proxy Villingen 210g anhydrous caffeine 75g Vitamin B ₁ nitrate 8g vitamin B ₂ 4g Lactose 300g Microcrystalline cellulose 290g Magnesium stearate 20 g Hardened castor oil 17 g Example 29 The following components were added to distilled water, and the mixture was stirred to be uniform. Then p
The pH was adjusted to 4.2 with an H adjuster (citrate buffer), and distilled water was added to make the total volume 50 L.

Naproxen 300 g Dihydrocodeine phosphate 24 g Epinastine hydrochloride 20 g dl-Methylephedrine hydrochloride 60 g Bromhexine hydrochloride 12 g Lysozyme chloride 60 g (titer) Anhydrous caffeine 50 g Vitamin C 100 g D-sorbitol 50 g Sodium citrate 5 g Polyoxyethylene cured g Fragrance Fine amount Comparative examples 1 to 10 Components and amounts shown in Tables 7 to 8 were weighed and prepared according to Example 1.

Test Example Effect of the Combined Preparation on Cough Symptoms Test Method Using ddY male rats, Examples 1 to 2
4. The drug of Comparative Examples 1 to 10 was orally administered 3 mL every 24 hours, 12 hours, and 1 hour before the following gas exposure. Then, d was mixed in a gas containing 2.5% sulfur dioxide.
The dY male rats were exposed for 5 seconds and the number of artificially generated coughing reactions per minute was measured. The inhibition rate was calculated from this value and a value obtained by performing the same operation for 3 mL of purified water, and the results were compared and evaluated. Table 1 summarizes these results.
8 is shown. From these results, it is clear that the preparation containing naproxen, ketoprofen, and diclofenac sodium combined with an antitussive had a remarkable inhibitory effect on the cough reaction. Similar results were observed when isopropylantipyrine was added.

[0026]

[Table 1]

[0027]

[Table 2]

[0028]

[Table 3]

[0029]

[Table 4]

[0030]

[Table 5]

[0031]

[Table 6]

[0032]

[Table 7]

[0033]

[Table 8]

[0034]

According to the present invention, the cough suppressing effect of the antitussive has been remarkably improved. As a result, it has become possible to provide a cough medicine useful for cold syndrome and the like.

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Claims (4)

[Claims] (1) an antitussive, (B) naproxen,
A cough medicine containing ketoprofen, diclofenac sodium or isopropylantipyrine. 2. The antitussive agent is codeine or a salt thereof, codeine analog or a salt thereof, xanthine analog, cloperastine or a salt thereof, tipepidine or a salt thereof, pentoxiverine or a salt thereof, or alloclamide or a salt thereof. Item 4. The cough medicine according to item 1. 3. The cough medicine according to claim 2, wherein the codeine analog is dihydrocodeine or a salt thereof, or dextromethorphan or a salt thereof. 4. The cough remedy according to claim 2, wherein the xanthine analog is theophylline, aminophylline, diprofylline or proxyphylline.