JPH06239763A - Medicine for cold - Google Patents

Abstract

PURPOSE:To promote the antitussive action and decrease the toxicity of a medicine for cold compounded with a central acting antitussive. CONSTITUTION:This medicine for cold contains three components consisting of ibuprofen, an expectorant and an antitussive as active components at the same time.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a cold medicine having an enhanced antitussive action.

[0002]

2. Description of the Related Art Conventionally, various cold medicines have been known, but none of them have a satisfactory antitussive effect and a satisfactory effect has not been obtained.

[0003]

Noscapine is widely used as an antitussive, but its action is weak and it is difficult to obtain a sufficient effect. On the other hand, dihydrocodeine phosphate has a strong action, but also has a strong side effect and is also addictive, and therefore there is a problem in prescribing an amount which can be expected to have its pharmacological action.

[0004]

Means for Solving the Problems As a result of studies aimed at enhancing the antitussive effect, the present inventors have found that ibuprofen and the expectorant bromhexine hydrochloride or ambroxol hydrochloride are treated with the central antitussive drug codeine phosphate or noscapine. It was found that the effects of these antitussives are enhanced by the combination, and the present invention has been completed. That is, the present invention is
Ibuprofen as an active ingredient, expectorant and antitussive 3
It is a cold medicine characterized by containing components.

The cold medicine of the present invention is usually 400 to 700 mg once a day for an adult as an active ingredient,
It can be administered orally in several divided doses. This dose can be appropriately increased or decreased depending on the age, body weight and medical condition.

Furthermore, the cold medicine of the present invention is used in the form of oral dosage forms such as tablets, granules, powders, capsules and liquids.

These preparations can be prepared by a conventional method. The carrier used in the preparation of the formulation, lactose,
Excipients such as starch, sugar, mannitol, crystalline cellulose, binders such as hydroxypropylcellulose, hydroxypropylmethylcellulose, gelatin, PVP, disintegrators such as calcium carboxymethylcellulose, low-substituted hydroxypropylcellulose, magnesium stearate, hardening There are lubricants such as castor oil and talc, and if necessary, solubilizing agents, buffers, preservatives, perfumes, dyes, corrigents and the like can be used.

[0008]

INDUSTRIAL APPLICABILITY As a result of enhancing the antitussive effect, the present invention can reduce the toxicity of the cold medicine containing the central antitussive agent codeine phosphate or noscapine.

[0009]

EXAMPLES The present invention will be described in more detail with reference to Examples and Test Examples.

Example 1 The following components and amounts were weighed and uniformly mixed, and then the obtained mixed powder was filled in a No. 2 hard capsule in an amount of 230 mg each.
6000 capsules were obtained. Ibuprofen 450g Bromhexine hydrochloride 12g Noscapine 48g Lactose 350g Microcrystalline cellulose 490g Talc 30g

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 230 mg to obtain 9000 tablets. Ibuprofen 450g Ambroxol hydrochloride 48g Noscapine 48g Lactose 800g Low-substituted hydroxypropylcellulose 694g Talc 20g Hardened castor oil 10g

Example 3 The following components and amounts were weighed and uniformly mixed, and 280 mg tablets (9000 pieces) were obtained according to Example 2. Ibuprofen 450g Bromhexine hydrochloride 12g Dihydrocodeine phosphate 24g Lactose 980g Low-substituted hydroxypropylcellulose 530g Microcrystalline cellulose 469g Talc 40g Hardened castor oil 15g

Example 4 The following components and amounts were weighed and uniformly mixed, and 290 mg tablets (290 mg) were obtained according to Example 2. Ibuprofen 450 g Ambroxol hydrochloride 48 g Dihydrocodeine phosphate 24 g Lactose 980 g Low-substituted hydroxypropyl cellulose 530 g Microcrystalline cellulose 523 g Talc 40 g Hydrogenated castor oil 15 g

Example 5 The following components and amounts were weighed and uniformly mixed, and 280 mg tablets (9000 mg) were obtained according to Example 2. Ibuprofen 450g Ambroxol hydrochloride 48g Noscapine 48g Chlorpheniramine maleate 7g Methylephedrine hydrochloride 60g Lactose 1200g Microcrystalline cellulose 652g Talc 40g Hardened castor oil 15g

Example 6 The following components and amounts were weighed and uniformly mixed, and 280 mg of 280 mg tablets were obtained according to Example 2. Ibuprofen 450g Bromhexine hydrochloride 12g Noscapine 36g Dextromethorphan hydrobromide 48g Carbinoxamine maleate 7g Methylephedrine hydrochloride 60g Lactose 500g Microcrystalline cellulose 522g Talc 30g Hardened castor oil 15g

Example 7 The following components and amounts were weighed and uniformly mixed, and 9000 pieces of 300 mg tablets were obtained according to Example 2. Ibuprofen 450g Bromhexine hydrochloride 12g Dihydrocodeine phosphate 24g Carbinoxamine maleate 7g Methylephedrine hydrochloride 60g Lactose 1200g Microcrystalline cellulose 887g Talc 40g Hardened castor oil 20g

Example 8 The following components and amounts were weighed and uniformly mixed, and then 290 mg of 290 mg tablets were obtained according to Example 2. Ibuprofen 450g Bromhexine hydrochloride 12g Dihydrocodeine phosphate 24g Noscapine 48g Carbinoxamine maleate 7g Methylephedrine hydrochloride 60g Lactose 1100g Microcrystalline cellulose 849g Talc 40g Hardened castor oil 20g

Test Example 1 [Antinociceptive action of the compounded preparation] (Experimental method) Male Hartley guinea pigs having a body weight of about 300 g were used in the experiment with 10 animals per group. The drug was orally administered as a suspension prepared in a 5% arabic gum solution. The method for inducing cough is the sulfurous acid gas method of Takagi and others (Pharmaceutical Development Basic Course,
The experiment was conducted according to the evaluation of drug efficacy (1) p345-347). That is, a certain amount of sulfurous acid gas (about 300 m) generated by placing a guinea pig in a sealed container of about 3 L and reacting concentrated sulfuric acid with a saturated solution of NaHSO3 (about 300 m
l) is fed into a container containing guinea pigs, after suctioning sulfurous acid gas for 1 minute, the guinea pigs are taken out of the container,
After that, the cough induced for 5 minutes was observed, and the antitussive action was examined using an animal that does not develop the cough as an effective example. Regarding animals that were previously inhaled with sulfurous acid gas and confirmed that coughing occurred, an effective example was an animal in which the same amount of sulfurous acid gas was inhaled 1 and 2 hours after the administration of the sample, and coughing disappeared in either one of them. The animals that induced cough in both doses were considered ineffective, and the cough inhibition rate was determined from the number of guinea pigs in each effective dose at each dose, and the 50% effective dose (ED50) of each formulation was determined by the Richfield-Wilcoxon method.

(Experimental Results) As shown in Table 1, ibuprofen (IP), ambroxol (AX) and bromhexine (BH) do not show antitussive activity when administered alone. The antitussive dose of dihydrocodeine hydrochloride (DC), a central antitussive, was 4.7 mg / kg. Next, the antitussive action of the combined preparation is
The antitussive effect was examined by fixing the doses of P (100 mg / kg, po), BH (3 mg / kg, po) and AX (10 mg / kg, po) and varying the dose of DC. As a result, IP and N
The combination of P, BH and DC and AX and DC does not affect the antitussive effect of CD, but IP + DC + BH and IP
The antitussive effect of DC was significantly enhanced by the combined use of + DC + AX (Table 1). These results suggest that the combined use of IP with a central antitussive and an expectorant may enhance the antitussive effect.

[0020]

[Table 1]

Ibuprofen (IP) 100 mg / k
The dose of g, bromhexine hydrochloride (BH) 3 mg / kg, and ambroxol 10 mg / kg were fixed, and the antitussive effect was examined by changing the dose of dihydrocodeine hydrochloride (DC). The numerical value is the antitussive effect amount of DC (ED50). Next, it was examined at what combination ratio the IP, central antitussive drug and expectorant drug had the strongest antitussive effect. That is, the antitussive action was examined by fixing the DC dose at 5 mg / kg and changing the compounding amounts of IP, BH and AX.

As a result, in the combination of IP + BH + DC, I
P: BH: DC = 90: 1: 5 (Table 2), IP + AX +
IP: AX: DC = 9: 1: 1 for DC formulation (Table 3)
Was considered to be the optimum mixing ratio.

[0023]

[Table 2]

[0024]

[Table 3]

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Claims (1)

[Claims] 1. A cold remedy characterized by containing, as active ingredients, three components of ibuprofen, an expectorant and an antitussive.