JP2004083596A - Cough and cold medicine - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a cough and cold medicine which, as the result of the enhanced antitussive action, is reduced in the toxicity associated with incorporation of a central-acting antitussive agent. <P>SOLUTION: The cough and cold medicine is characterized by concurrent incorporation of three ingredients of ibuprofen, an expectorant, and an antitussive as the effective ingredients. <P>COPYRIGHT: (C)2004,JPO

Description

(4) The present invention relates to a cold remedy having an enhanced antitussive effect.

多 Various types of common cold medicines have been known, but none of them has a satisfactory antitussive effect and satisfactory effect has not been obtained.

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

The present inventors have conducted studies with the aim of enhancing the antitussive effect. The present inventors have found that the effect of the drug is enhanced and completed the present invention.

That is, the present invention is a cold medicine characterized by mixing three components of ibuprofen, expectorant and antitussive as active ingredients.

According to the present invention, as a result of enhancing the antitussive action, it is possible to reduce the toxicity of a cold medicine containing a central antitussive, codeine phosphate or noscapine.

感 Usually, the cold remedy of the present invention can be orally administered to an adult at a dose of 400 to 70 mg as an active ingredient once or several times a day. This dose can be appropriately increased or decreased depending on age, body weight, and medical condition.

Furthermore, the cold remedy of the present invention is used as a preparation for oral administration such as tablets, granules, powders, capsules and liquids.

製 剤 These preparations can be prepared by a conventional method. Carriers used in the preparation of formulations include excipients such as lactose, starch, sugar, mannitol, crystalline cellulose, binders such as hydroxypropylcellulose, hydroxypropylmethylcellulose, gelatin, PVP, carboxymethylcellulose calcium, low-substituted hydroxy. There are disintegrators such as propylcellulose, lubricating agents such as magnesium stearisate, hydrogenated castor oil, and talc.In addition, if necessary, use a solubilizing agent, a buffer, a preservative, a flavor, a pigment, a flavoring agent, etc. be able to.

本 Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples.

Example 1
After the following components and amounts were weighed and uniformly mixed, 230 mg of the obtained mixed powder was filled into No. 2 hard capsules to obtain 6000 capsules.

450 g of ibuprofen
Bromhexine hydrochloride 12g
Noscapine 48g
Lactose 350g
490 g microcrystalline cellulose
Talc 30g

Example 2
After weighing and uniformly mixing the following components and amounts, the obtained mixed powder was tableted by a direct compression method so that the weight of one tablet was 230 mg, and 9000 tablets were obtained.
450 g of ibuprofen
Ambroxol hydrochloride 48g
Noscapine 48g
Lactose 800g
Low-substituted hydroxypropyl cellulose 694g
20g talc
Hardened castor oil 10g

Example 3
After weighing and uniformly mixing the following components and amounts, according to Example 2, 9,000 tablets of 280 mg were obtained.
450 g of ibuprofen
Bromhexine hydrochloride 12g
24g dihydrocodeine phosphate
Lactose 980g
Low substituted hydroxypropylcellulose 530g
469g microcrystalline cellulose
Talc 40g
Hardened castor oil 15g

Example 4
The following components and amounts were weighed and uniformly mixed. According to Example 2, 9000 mg tablets of 290 mg were obtained.
450 g of ibuprofen
Ambroxol hydrochloride 48g
24g dihydrocodeine phosphate
Lactose 980g
Low substituted hydroxypropylcellulose 530g
Microcrystalline cellulose 523g
Talc 40g
Hardened castor oil 15g

Example 5
After weighing and uniformly mixing the following components and amounts, according to Example 2, 9,000 tablets of 280 mg were obtained.
450 g of ibuprofen
Ambroxol hydrochloride 48g
Noscapine 48g
Chlorpheniramine maleate 7g
Methylephedrine hydrochloride 60g
Lactose 1200g
652 g microcrystalline cellulose
Talc 40g
Hardened castor oil 15g

Example 6
The following components and amounts were weighed and uniformly mixed, and 6,000 tablets of 280 mg were obtained according to Example 2.
450 g of ibuprofen
Bromhexine hydrochloride 12g
Noscapine 36g
Dextromethorphan hydrobromide 48g
Carbinoxamine maleate 7g
Methylephedrine hydrochloride 60g
Lactose 500g
Microcrystalline cellulose 522g
Krk 30g
Hardened castor oil 15g

Example 7
After weighing and uniformly mixing the following components and amounts, 300 mg according to Example 2.
9000 tablets were obtained.
450 g of ibuprofen
Bromhexine hydrochloride 12g
24g dihydrocodeine phosphate
Carbinoxamine maleate 7g
Methylephedrine hydrochloride 60g
Lactose 1200g
887g of microcrystalline cellulose
Krk 40g
Hardened castor oil 20g

Example 8
The following components and amounts were weighed and uniformly mixed. According to Example 2, 9000 mg tablets of 290 mg were obtained.
450 g of ibuprofen
Bromhexicine hydrochloride 12g
24g dihydrocodeine phosphate
Noscapine 4g
Carbinoxamine maleate 7g
Methylephedrine hydrochloride 60g
Lactose 1100g
849 g of microcrystalline cellulose
Talc 40g
Hardened castor oil 20g

Test example 1
[Anti-coughing action of combination preparation]
(experimental method)
Male Hartley guinea pigs weighing about 300 g were used for the experiment in 10 animals per county. The drug was orally administered as a suspension prepared in a 5% arabic gum solution. The cough was induced in accordance with the sulfite gas method of Takagi et al. (Basic Course in Drug Development, Evaluation of Drug Efficacy (1), p. That is, a guinea pig is placed in a closed container of about 3 L, and a certain amount (about 300 ml) of sulfur dioxide generated by reacting concentrated sulfuric acid with a saturated solution of NaHSO3 is sent to the container containing the guinea pig. After inhaling sulfur dioxide for 1 minute, the guinea pig was taken out of the container, and then cough induced for 5 minutes was observed, and the coughing effect was examined in animals that did not develop cough as an effective example. For animals that inhaled sulfur dioxide in advance and confirmed that coughing had occurred, animals that inhaled the same amount of sulfur dioxide 1 and 2 hours after the administration of the specimen, and animals in which cough disappeared in either one were effective cases, Animals that had coughed twice were regarded as ineffective, and the cough suppression rate was determined from the number of guinea pigs in the effective cases at each dose, and the 50% effective dose (ED50) of each formulation was determined by the Richfield-Wilcoxon method.

(Experimental result)
As shown in Table 1, ibuprofen (IP), amproxol (AX) and bromohexine (BH) do not show an antitussive effect when administered alone. The cough dose of the central antitussive dihydrocodeine hydrochloride (DC) was 4.7 mg / kg.

Next, the antitussive action of the combined preparation was measured by fixing the doses of IP (100 mg / kg, po), BH (3 mg / kg, po) and AX (10 mg / kg, po) in DC. The antitussive effect was examined by changing the dose of. As a result, the antitussive effect of DC was not affected by the combination of IP and DC, BH and DC or AX and DC, but the coughing effect of DC was dramatically enhanced by the combination of IP + DC + BH and IP + DC + AX (Table 1). 1).

These results suggest that the combined use of IP and central antitussives and expectorants may enhance the antitussive effect.

The doses of 100 mg / kg of ibuprofen (IP), 3 mg / kg of bromhexine hydrochloride (BH) and 10 mg / kg of ambroxol were fixed, and the antitussive effect was examined by changing the dose of dihydrocodeine hydrochloride (DC). The figures are the antitussive effect of DC (ED50)
Next, the coughing effect of the combination of IP, central antitussive and expectorant was examined to determine the combination ratio at which the strongest coughing effect was obtained. That is, the dose of DC was fixed to 5 mg / kg, and the coughing action was examined by changing the blending amount of IP, BH and AX. As a result, in the blending of IP + BH + DC, IP: BH: DC = 40: 2: 5 ( In the composition of Table 2) and IP + AX + DC, the composition of IP: AX: DC = 9: 1: 1 (Table 3) was considered to be the optimal composition ratio.

Claims (1)

A cold medicine characterized by combining three components of ibuprofen, expectorant and chain cough as active ingredients.