JP2013121948A - Common cold drug improved in drowsiness - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a common cold drug excellent in improving effects of various symptoms of a common cold, and reduced in drowsiness.SOLUTION: An oral common cold drug composition containing an isopropylantipyrine, a dihydrocodeine phosphate, a methylephedrine hydrochloride, a caffeine, and an antihistamine that may cause drowsiness additionally contains an isopropamide iodide.

Description

  The present invention contains isopropylantipyrine, acetaminophen, chlorpheniramine maleate, dihydrocodeine phosphate, dl-methylephedrine hydrochloride, caffeine, and licorice extract, and further contains an oral isopropamide. The present invention relates to a pharmaceutical composition.

  In addition to (A) antipyretic analgesics, which are essential ingredients, (B) antihistamines, (C) antitussives, (D) noscapine, (E) bronchodilators, (F) expectorants, (G) Caffeine, (H) vitamins, (I) mucosal protective components, and (J) herbal medicines may be blended. Efficacy that can be described in general cold medicine is relief of cold symptoms (nasal discharge, nasal congestion, sneezing, sore throat, cough, sputum, chills, fever, headache, joint pain, muscle pain) (B ) Does not contain the effects of runny nose, nasal congestion, and sneezing, and if it does not contain (C) to (E), it does not contain coughing effects, and (F) or other components having expectorant action In this case, the effect of sputum cannot be described (for example, see Non-Patent Document 1).

Since runny nose, nasal congestion, and sneezing are the main symptoms of colds, most common cold drugs contain the antihistamine (B). However, antihistamines may cause sleepiness by simultaneously blocking histamine, which is also a brain arousal substance, and there is a problem in that it requires attention when taking cautions such as lowering work efficiency while driving and driving .
Since cough is also a major symptom of colds, codeine, an antitussive component, is often included, but since codeines have central nervous system inhibitory effects, respiratory depression and sleepiness are important basics when taking medicine. It was a precaution (see Non-Patent Document 2, for example).

  The anticholinergic iodopropamide is used as an active ingredient in gastrointestinal and rhinitis drugs because it has been shown to suppress bronchomuscular contraction, gastrointestinal spasm, nasal secretion and excessive secretion of gastric juice (For example, refer to Patent Document 1). Since it is a component that strongly suppresses runny nose, it is a standard component (see Non-Patent Document 1) that can be blended in internal medicine for rhinitis in over-the-counter medicines, and it is sometimes rarely blended in cold medicine. . However, it is not known that isopropamide iodide has drowsiness and vice versa.

JP-A-8-325142

OTC Drug Manufacturing (Import) Approval Criteria 2000 Jiho 2000 2009 Edition Prescription Drug Collection JAPIC 2008

  An object of the present invention is to provide a cold medicine having a better effect of improving various symptoms of cold. More specifically, it is to provide a general cold medicine that has an excellent effect of suppressing runny nose (nasal discharge).

In order to enhance the antipyretic analgesic effect, the present inventors added dihydrocodeine phosphate, dl-methylephedrine hydrochloride, caffeine, licorice extract, in addition to two types of antipyretic analgesic components, isopropylantipyrine and acetaminophen, Although we have found an oral cold medicine containing chlorpheniramine maleate, we have conducted extensive research on a common cold medicine that has further enhanced the effect of nasal discharge.
As a result, when isopropamide iodide, which is a kind of anticholinergic agent, is further added to the cold medicine prescription, it is surprising that sleepiness, which is an undesirable effect of antihistamines, etc. It has been found that the effect of reducing the above is manifested, and the present invention has been completed.
That is, the present invention provides the following (1) to (4).
(1) In a composition containing isopropylantipyrine, dihydrocodeine phosphate, dl-methylephedrine hydrochloride, caffeine, and an antihistamine that may cause drowsiness,
An oral cold medicine composition characterized by further containing iodopropamide iodide.
(2) In a composition containing isopropylantipyrine, acetaminophen, dihydrocodeine phosphate, dl-methylephedrine hydrochloride, caffeine, licorice extract, and an antihistamine that may cause drowsiness,
An oral cold medicine composition characterized by further containing iodopropamide iodide.
(3) The oral cold medicine composition according to (1) or (2), wherein the antihistamine that may cause drowsiness is chlorpheniramine maleate.
(4) The oral cold medicine composition according to any one of (1) to (3), wherein drowsiness is improved.

  The oral cold medicine composition of the present invention is useful because it reduces not only excellent nasal discharge, but also drowsiness, which is an undesirable action such as antihistamines.

  Isopropylantipyrine, acetaminophen, dihydrocodeine phosphate, dl-methylephedrine hydrochloride, caffeine (anhydrous caffeine or caffeine hydrate), chlorpheniramine maleate, licorice (licorice, licorice) Powder or licorice extract) is listed in the 16th revised Japanese Pharmacopoeia, and isopropamide iodide is listed in the Japanese Pharmacopoeia Standard 2002.

  The contents of isopropylantipyrine, acetaminophen, dihydrocodeine phosphate, dl-methylephedrine hydrochloride, caffeine, chlorpheniramine maleate, and licorice extract in the composition of the present invention are not particularly limited, but for general use It is desirable that it is within the standards for approval of pharmaceutical manufacture (import) or within the range of precedents in combination.

About isopropamide iodide, Preferably it should just set so that 1-15 mg, More preferably, 3-9 mg can be taken in 1 to 3 times a day.
For example, if the composition of the present invention is a solution taken 10 mL three times a day, the content of iodopropamide in the solution is preferably 0.3 to 5 mg / 10 mL, more preferably 1 to 3 mg / 10 mL. is there.

  In the composition of the present invention, other herbal medicines, vitamins, antacids, excipients, binders, lubricants, coating agents, preservatives, colorants, stable, as long as the effects of the present invention are not inhibited. An agent, a pH adjuster, a solubilizer, a refreshing agent, a fragrance, a pigment / colorant, and the like can be blended.

  The composition of the present invention can be produced by a method known in the art. For example, in the case where the composition of the present invention is a tablet, it can be produced according to the section of the Japanese Pharmacopoeia General Rules “Tablets”. Moreover, when it is a liquid agent, it can be manufactured according to the section of the Japanese Pharmacopoeia General Rules “Liquid Agent”.

  Examples of the present invention are described below, but are not limited thereto.

(Example 1) Capsule The ingredients and amounts shown in Table 1 are taken, and a capsule is produced according to the section “General Capsule” of the Japanese Pharmacopoeia.

(Example 2) Solution The ingredients and amounts shown in Table 2 are taken, and a tablet is produced according to the section of “General Preparations” “Liquid”.

(Test example) Single-dose test (1) Test substance Isopropylantipyrine, acetaminophen, dihydrocodeine phosphate, dl-methylephedrine hydrochloride, anhydrous caffeine, chlorpheniramine maleate, licorice extract In addition, isopropamide iodide was manufactured by Nippon Bulk Chemical Co., Ltd.
The components shown in Table 1 as test substances were suspended in 0.5% CMC (0.5% sodium carboxymethylcellulose solution) to prepare a 100 mg / mL administration solution.
Moreover, what added lactose instead of the isopropamide iodide as a comparative substance was manufactured similarly.

(2) Experimental animals
Sprague-Dawley male and female rats, 5 weeks old, were purchased from Nippon Charles River Co., Ltd., preliminarily raised for 1 week, and then used in the experiment those which were not abnormal in general condition. Grouping was performed on the day before the administration day, and based on the body weight on the day of grouping, 3 animals were grouped so that the average body weight was as uniform as possible.

(3) Administration of test substance The administration dose was 10 mL / Kg body weight, and a single forced oral administration was performed using a flexible gastric sonde. The control group received vehicle (0.5% CMC).

(4) Test results The results of spontaneous exercise and respiratory rate reduction obtained are shown in Tables 3-5.

In the test substance group, the duration of onset of decreased locomotor activity corresponding to sleepiness and fatigue was shortened.

In the test substance group, the duration of onset of decreased locomotor activity corresponding to sleepiness and fatigue was shortened.

In the test substance group, there was no decrease in respiratory rate corresponding to sleepiness.

  From the above results, it was found that the symptoms corresponding to the drowsiness and malaise of antihistamines were improved by adding isopropamide iodide.

  It can be used as a general cold medicine composition with reduced drowsiness.

Claims (4)

In a composition comprising isopropylantipyrine, dihydrocodeine phosphate, dl-methylephedrine hydrochloride, caffeine, and an antihistamine that can cause drowsiness,
An oral cold medicine composition characterized by further containing iodopropamide iodide. In a composition comprising isopropylantipyrine, acetaminophen, dihydrocodeine phosphate, dl-methylephedrine hydrochloride, caffeine, licorice extract, and an antihistamine that may cause drowsiness,
An oral cold medicine composition characterized by further containing iodopropamide iodide.   The oral cold medicine composition according to claim 1 or 2, wherein the antihistamine that may cause drowsiness is chlorpheniramine maleate.   The oral cold medicine composition according to any one of claims 1 to 3, wherein drowsiness is improved.