CN105287554B - Compounded anti-cold drug composition and application thereof - Google Patents

Abstract

The present invention relates to the combinations of the compound medicine of anti-common cold treatment, the composition by physiologically effective dose brufen and its pharmaceutically acceptable salt, fexofenadine and its pharmaceutically acceptable salt, benproperine and its pharmaceutically acceptable salt and be medicinal active ingredient main body, be aided with pharmaceutically acceptable auxiliary material composition.Using above-mentioned tripartite coalition medication, have side effect low, rapid-action, act synergistically good feature, is mainly used for treatment flu intermediary and later stages symptom.

Description

Compounded anti-cold drug composition and application thereof

Technical field

The present invention relates to field of medicaments, more particularly to compound cold-treating medicine composition and application thereof.

Background technology

In worldwide, flu is relatively conventional disease, and Coritab is then natural to be become using most frequency One of numerous, maximum drug of usage amount.The composition of Coritab component generally can be divided into following several types, antipyretic-antalgic at Point, antibechic ingredient and antihistamine.

Cold drug containing antihistamine ingredient such as chlorphenamine, diphenhydramine etc., which has, causes drowsiness side effect, driver, height Idle job person, fine work post operator should not take, and at least daytime is unusable.

Cold drug containing antipyretic-antalgic ingredient such as Diclofenac, not with gastric and duodenal ulcer person, hepatic and renal function Quan Zhe, pregnant woman, children cannot use；Cold drug excessive use containing aspirin, can cause pH value of blood to decline, in appearance Pivot nervous system symptom, while can stimulate respiratory center and vomiting centre causes to be short of breath, nausea and vomiting, and because of the 8th pair of brain Nerve is stimulated and causes tinnitus, deafness.Paracetamol is excessive or being used for a long time can cause acute nephritis or glomerulus bad It waits indefinitely nephrotic syndrome, or even can also result in renal failure.Take C14H10Cl2NNaO2, aspirin to the damage of gastric mucosa compared with Greatly, it easily causes bleeding.C14H10Cl2NNaO2, paracetamol, aspirin are likely to that granulocyte is caused to reduce.

Dextromethorphan in kobadrin composition has the function of central cough-relieving, antibechic, relievings asthma, but can cause nausea, Gastrointestinal irritations, pregnant woman, dyshepatia and more phlegm persons such as vomiting, stomachache use with caution.

Cold drug market drug variety is more at present, but advertisement exaggerates next, and multiple adverse reaction is that we face Matter of utmost importance, and avoid the mode of adverse drug reaction should be to select toxic side effect low, small dosage is new R&D direction.

Invention content

The object of the present invention is to provide a kind of curative for effect, compounded anti-cold drug compositions of Small side effects.

Technical scheme is as follows：

Using brufen, fexofenadine, benproperine combination for middle and later periods symptomatic treatment of catching a cold, wherein brufen exists It is safely and effectively antipyretic in clinical application, its effect of bringing down a fever is brighter than the paracetamol of same dosage when body temperature is higher than 39.2 DEG C It is aobvious, and fever time is longer；Since the advent of the world more than aspirin, phenylbutazone and is flutterred because of the effect that its is anti-inflammatory, alleviates pain, brings down a fever Heat breath pain is strong, and popular with consumers again.The side effect of brufen is smaller, is only limited to slight indigestion, fash, transaminase liter It is high and extremely rare, it is children's antipyretic that the World Health Organization, U.S. FDA are uniquely recommended jointly, is generally acknowledged children Preferred antipyretic.

Fexofenadine is third generation Claritin, have will not cause cardiac toxic, antiallergic effect it is stronger, Safety higher does not lead to drowsiness feature, and being set to pilot under state on duty by flight management office of the United States Federal can make Claritin.

Benproperine antitussive effect is stronger, is non-narcotic anti-tussive agents, has dual antitussive effect, mechanism of action mainly to hinder Lung-vagus reflex that the stretch receptor of disconnected lung-pleura generates, has both central and peripheral double mechanism.Irritation Dry cough person is applicable in especially, and antitussive effect is 2-4 times strong compared with codeine.Treatment flu dosage is low, rapid-action, gives birth within 15-20 minutes after clothes Effect, duration grow (4-7 hours).

Treatment flu in principle should with rest more, drink more water, improve diet, have a breath of fresh air more based on, in flu Later stage is to avoid delaying normal work and study, must avoid overweight headache, fever, cough using quickly and effectively anti-sense drug It coughs, have aches in the limbs, the intermediary and later stages symptom such as courbature, general malaise.Using above-mentioned tripartite coalition medication, have side effect low, rises Effect is fast, and act synergistically good feature, is mainly used for the alleviation for the treatment of flu intermediary and later stages symptom.

The present invention compounded anti-cold drug composition by brufen and its pharmaceutically acceptable salt, fexofenadine and Its pharmaceutically acceptable salt, benproperine and its pharmaceutically acceptable salt form.

The brufen and its pharmaceutically acceptable salt, fexofenadine and its pharmaceutically acceptable salt, Benproperine and its pharmaceutically weight ratio of acceptable salt are 1：1-4：0.5-4, preferred scope 1：1-2：0.5-2.

Further, the amount of brufen is 15-100mg in composition.

The amount of the fexofenadine is 15-75mg.

The amount of the benproperine is 10-50mg.

The compound can be prepared into clinically acceptable oral preparation with pharmaceutically acceptable carrier.Institute The oral preparation stated is tablet, capsule, granule or suspension.

The pharmaceutically acceptable carrier includes filler, adhesive, disintegrant, lubricant and surfactant.

In the present invention, actively progress effect is that three medicines are used in combination, and effect is better than the treatment of folk prescription same dose Effect has fully demonstrated the synergistic effect between drug, it is possible to reduce the dosage of drug reduces what toxicity adverse reaction occurred It may.

Specific implementation mode：

Embodiment 1：

Experimental method：

Take KM kinds mouse 30, laboratory environment (feeding environment：18~25 DEG C of temperature) adaptability raise 3 days.Random point It is 3 groups, every group 10.It is numbered after weighing.Group 1 is blank control group, and group 2 gives compound patulin composition prescription one (Bu Luo Fragrant 30mg, fexofenadine 30mg, benproperine 30mg), group 3 gives benproperine phosphate 60mg/kg,.Mouse is before experiment 8h fasting, freely takes the photograph water.By 0.1ml/10g dosage, gastric infusion, this operation is completed in 2 minutes.Administration carries out after 30 minutes Ammonium hydroxide draws cough experiment.0.3ml ammonium hydroxide is drawn, notes in cotton balls, 150s in beaker will be buckled in together with cotton balls and mouse, observe and remember Record the cough number and cough latent period of mouse.Cough is shown as：It is with cough, visible abdominal muscle to magnify mouth or an osculum It shrinks.Incubation period shows as：Time of the mouse since phenomenon of coughing to first time appearance experiment.Blank group method is identical.Knot Fruit carries out T inspections.

As a result：

Compound flu reagent and benproperine phosphate draw cough antitussive effect to mouse ammonium hydroxide

	Incubation period	Cough number
			Blank	57.5±9.28	21.2±1.83
Compound cold drug	103±24.5**	4.6±2.7***
			Benproperine phosphate	75.5±20.9**	17.3±5.94**

**P<0.01, * * * P<0.001VS blank groups

Conclusion：Compound cold drug can be obviously prolonged cough latent period, and cough number is made to reduce, and antitussive effect is better than high dose Benproperine phosphate.

Embodiment 2：

Experimental method：

Take KM kinds mouse 30, laboratory environment (feeding environment：18~25 DEG C of temperature) adaptability raise 3 days.Random point It is 3 groups, every group 10.It is numbered after weighing.Group 1 is blank control group, and group 2 gives compound patulin composition prescription one (Bu Luo Fragrant 30mg, fexofenadine 30mg, benproperine 60mg), group 3 gives brufen 30mg/kg.The equal gastric infusion of drug, administration 0.5h smears croton oil proinflammatory agent to each group mouse right ear two sides afterwards.Mouse is taken off neck after administration 2h to put to death, with 0.7mm card punch Under chisel, two auricles of left and right are weighed.Using swelling value [(auris dextra weighs a left ear weight)/left ear weight × 100%] as index, t examines system Data between meter group evaluate drug effect.

As a result：

Compound flu reagent and brufen cause scorching ear swelling rate to mouse knoting oil

	Ear swelling rate %
		Blank	42.2±29.8
Compound cold drug	26.9±28.4*
		Brufen	34.2±27.6

*P<0.05VS blank groups

Conclusion：The anti-inflammatory effect of brufen can be remarkably reinforced in compound cold drug, and effect is better than the same as dosage brufen.

Embodiment 3：

Experimental method：

Take cavy 18, laboratory environment (feeding environment：18~25 DEG C of temperature) adaptability raise 3 days.It is randomly divided into 3 Group, every group 6.Citric acid is dissolved into after being made into the concentration of 0.1M in physiological saline, these cavys are exposed to atomization lemon Lower 10 minutes of acid environment counts the cough number being exposed in this 10 minutes of environment, and according to its number of coughing How many packet numberings of weighing.Group 1 is blank control group, and group 2 gives compound patulin composition prescription one (brufen 1mg, non-rope Fei Nading 2mg, benproperine 1mg), group 3 gives fexofenadine 2mg/kg.Next day after citric acid stimulation, the equal gavage of drug are given Medicine, 1h sucks 6uM ATP aerosols after administration.Aerosol is generated using a ultrasonic ultrasonic delay line memory, per minute to be atomized about These cavys are exposed in ATP aerosols 2 minutes by the solution of 0.6ml.This process need to before sucking citric acid 5 minutes it Interior completion.Citric acid is dissolved into after being made into the concentration of 0.1M in physiological saline, these cavys are exposed to atomization citric acid ring Lower 10 minutes of border.It counts and calculates after being counted to the cough number being exposed in this 10 minutes of environment.As a result T inspections are carried out It tests.

As a result：

Compound flu reagent and fexofenadine lead to ATP- citric acids the protective effect of allergic cough.

	Cough number
		Blank	15.3±1.4
Compound cold drug	6.5±0.9*
		Fexofenadine	11.2±1.3*

*P<0.05VS blank groups

Conclusion：The pre- hypo-allergenic effect of fexofenadine can be remarkably reinforced in compound cold drug, and effect is better than the same as the non-rope of dosage Fei Nading.

One composite tablet of prescription：

Ingredient	Dosage
		Brufen	30g
Fexofenadine	30g
		Benproperine	30g
Microcrystalline cellulose	60g
		Pregelatinized starch	15g
Lactose	30g
		Odium stearate	2.5g
95% ethyl alcohol	In right amount
		It is made altogether	1000

Two compound capsule of prescription：

Component	Dosage
		Brufen	30g
Fexofenadine	30g
		Benproperine	30g
Microcrystalline cellulose	85g
		0.5%PVP-k30 ethanol solutions	In right amount
Talcum powder	3.5g
		It is made altogether	1000

Three compound granule of prescription：

Component	Dosage
		Brufen	30g
Fexofenadine	30g
		Benproperine	30g
Sucrose	42g
		Stevioside	7g
Dextrin	14g
		95% ethyl alcohol	In right amount

Four compound suspension of prescription：

Component	Dosage
		Brufen	30g
Fexofenadine	30g
		Benproperine	30g
Excipient	29.0%~99.3%
		Suspending agent	0.05%~36.4%
Fragrant corrigent	75~95%

Antifoaming agent	In right amount
		Surfactant	In right amount

Excipient can be any one of sucrose, mannitol, lactose, microcrystalline cellulose or two kinds or more

Suspending agent can be xanthans, Arabic gum, tragcanth, carbomer, povidone, hydroxypropyl methyl cellulose, Methylcellulose, sodium carboxymethylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, cellulose acetate, hydroxypropyl methyl fiber Plain acetate, hydroxypropyl methylcellulose phthalate, polyacrylic resin, polyvinyl alcohol, polyethylene glycol or chitin Any one of or two kinds or more.

Fragrant corrigent, corrigent select solid powder essence：Strawberry powdered flavor, cherry powdered flavor, orange powder Essence and mango powdered flavor, liquid essence：Strawberry liquid essence, apple powder essence, banana liquid essence, chocolate liquid Essence, vanilla fluid essence and mango liquid essence, saccharin sodium, aspartame, sucrose, mannitol, Stevioside；Colorant is coloured Element or color ingot：Any one of red pigments, xanthein, brown pigmentation, sunset yellow aluminium color ingot or two kinds or more.

Antifoaming agent selects any one of silicone oil, dimeticone or two kinds.

Surfactant proper amount of surfactant selects any one of lauryl sodium sulfate, polyoxyethylene sorbitan monoleate or two Kind.

Embodiment provided by the present invention is only to help to understand technical solution provided by the present invention, and cannot limit Protection scope of the present invention；The invention can be implmented in many different forms as is defined and embodied by the claims.

It the above is only the preferred embodiment of the present invention, it should be pointed out that those skilled in the art are come It says, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications also should be regarded as Protection scope of the present invention.

Claims (4)

1. a kind of compounded anti-cold drug composition, which is characterized in that the composition by physiologically effective dose brufen or medicine Acceptable salt 30mg on, fexofenadine or pharmaceutically acceptable salt 30mg, benproperine or pharmaceutically can be with The salt 30mg compositions of receiving.

2. composition according to claim 1, which is characterized in that the composition and pharmaceutically acceptable carrier knot Conjunction is prepared into clinically acceptable oral preparation.

3. composition according to claim 2, which is characterized in that the oral preparation be tablet, capsule, granule or Suspension.

4. application of the claim 1-3 any one of them composition in preparing treatment cold disease and cough suppressing medicine.