CN104623068B

CN104623068B - Treat medicine of fever in children infantile convulsion and preparation method thereof

Info

Publication number: CN104623068B
Application number: CN201510010152.4A
Authority: CN
Inventors: 刘莉; 王海洋; 张仕林; 尚秘; 费越
Original assignee: Dechangxiang Medical Industry Co Ltd Guiyang
Current assignee: Guizhou Dechangxiang Pharmaceutical Co ltd
Priority date: 2015-01-09
Filing date: 2015-01-09
Publication date: 2018-02-02
Anticipated expiration: 2035-01-09
Also published as: CN104623068A

Abstract

The invention discloses a kind of medicine for treating fever in children infantile convulsion, mainly it is made by the coptis, PULVIS CORNUS BUBALI CONCEN TRATUS, cornu caprae hircus, calamitas urinae hominis, Fermented Soybean, folium isatidis, schizonepeta, notopterygium root, the root of kudzu vine, glutinous rehmannia, caulis clematidis armandii, the radix paeoniae rubrathe, radix scutellariae, the root of purple-flowered peucedanum, radix scrophulariae, balloonflower root, radix bupleuri, Chinese tamarisk tops, rattletop and great burdock achene.The medicine has the effect of clearing heat and detoxicating, saturating table slit phlegm.For acute infantile convulsion, night fever is faced in typhoid fever heating, urine band blood, dimly visible do not go out of measles and cause body heat cough；Dysentery characterized by blood in the stool, watery diarrhea, dyspepsia, stomachache.It is evident in efficacy, Small side effects.

Description

Treat medicine of fever in children infantile convulsion and preparation method thereof

Technical field

The present invention relates to a kind of medicine for treating fever in children infantile convulsion and preparation method thereof, belong to the field of medicine technology.

Background technology

Infantile convulsion by heresy plague during diseases caused by external factors, is inside accumulate more, and phlegm warm-served food product and being terrified suddenly cause, and ailment said due to cold or exposure phlegm is stagnant, stops up in channels and collaterals liver Caused by arteries and veins arrested anxious.Symptom have mesh long not under, soon white of the eye, and opisthotonos, asthma, ululation do not go out, and appearance is helvolus, is held under the arm by nausea Heat, exerts a pernicious influence heart spleen therefore makes the strong lip of tongue blue or green, the symptoms such as poly- mouth hair is prohibited.Hyperpyrexia and infantile convulsion refer to due to high fever cause convulsions exhausting faint, It is a kind of clinically common disease, clinic is mainly shown as whole body or local tatanic and clonic twitches.Duration of seizure can By the several seconds to several minutes, while lose consciously, severe patient can repeatedly or persistently break out.Any season can occur, and be mainly in Children, the age is smaller, and the incidence of disease is higher.Its card feelings is often more dangerous, and change is rapid, threatens children's life.Infantile hyperpyrexia is shied Wind is that the children of 6 months to 3 years old are occurred mainly in caused by its nervous system development is immature, is one of common acute disease, can There is family history, much more general when disease rises from the beginning of, body temperature, heating companion's coolness of extremities, easily occur during complexion burnt hair, Can recurrent exerbation, repeatedly faint from fear after cause cerebral anoxia, influence Growth of Intelligence in Children.

The infection of the upper respiratory tract is most commonly seen disease, often causes heating by diseases caused by external factors, cough phlegm is yellow, asthma, abscess of throat Etc. symptom.Pediatric patient is common in, fever caused by exogenous pathogens can influence the life and normal development of patient.Traditional Chinese Medicine is thought：Because of wind-heat Caused cough is " hot cough ", and cardinal symptom is that phlegm is thick and yellow, and also band is yellow for nasal mucus, at this moment will be with the medicine of cool cold matter come handle Heat drop in human body gets off；And " cold cough " just is caused by chill, the abundant expectoration of patient is white and thin, and having a running nose is also Clear water sample, such patient must just dispel internal cold air with mild medicine.Cough is the most common one kind of breathing problem Symptom.Cough is a kind of protectiveness defense function of human body.By cough, the secretion of respiratory tract can be discharged or invade tracheal strips Foreign matter.Only cough and be referred to as dry cough without phlegm, it is seen that in a variety of diseases.

At present, in the market treatment acute infantile convulsion, typhoid fever heating, face the diseases such as night fever, transfusion is often equipped with Western medicine Treatment, but this kind of side effects of pharmaceutical drugs are big, especially for children, are not easy long-term use.Therefore, a side effect is studied Small, the medicine that can effectively treat fever in children infantile convulsion has realistic meaning.

The content of the invention：

The technical problems to be solved by the invention are to provide a kind of medicine for treating fever in children infantile convulsion and its preparation side Method.The medicine has the effect of clearing heat and detoxicating, saturating table slit phlegm.For acute infantile convulsion, typhoid fever heating, face night fever, urine band Blood, dimly visible do not go out of measles and cause body heat cough；Dysentery characterized by blood in the stool, watery diarrhea, dyspepsia, stomachache.It is evident in efficacy, Small side effects.

In order to solve the above technical problems, the present invention is realized using following technical scheme：

A kind of medicine for treating fever in children infantile convulsion, is calculated in parts by weight, is mainly concentrated by coptis 5-85 parts, cornu bubali Powder 10-120 parts, cornu caprae hircus 5-85 parts, calamitas urinae hominis (forge) 5-85 parts, Fermented Soybean 5-85 parts, folium isatidis 10-120 parts, schizonepeta 10- 120 parts, notopterygium root 10-120 parts, root of kudzu vine 10-120 parts, glutinous rehmannia 10-120 parts, caulis clematidis armandii 10-120 parts, radix paeoniae rubrathe 10-120 parts, Huang A kind of reed mentioned in ancient books 10-120 parts, root of purple-flowered peucedanum 20-150 parts, radix scrophulariae 20-150 parts, balloonflower root 20-150 parts, radix bupleuri 5-90 parts, Chinese tamarisk tops 5-90 parts, liter Numb 5-60 parts, great burdock achene (stir-fry) 20-150 parts and auxiliary material are prepared.

The medicine of aforementioned therapies fever in children infantile convulsion, is calculated in parts by weight, mainly dense by coptis 10-40 parts, cornu bubali Contracting powder 20-80 parts, cornu caprae hircus 10-40 parts, calamitas urinae hominis (forge) 10-40 parts, Fermented Soybean 10-40 parts, folium isatidis 20-80 parts, schizonepeta 20-80 parts, notopterygium root 20-80 parts, root of kudzu vine 20-80 parts, glutinous rehmannia 20-80 parts, caulis clematidis armandii 20-80 parts, radix paeoniae rubrathe 20-80 parts, radix scutellariae 20-80 parts, root of purple-flowered peucedanum 40-110 parts, radix scrophulariae 40-110 parts, balloonflower root 40-110 parts, radix bupleuri 20-60 parts, Chinese tamarisk tops 20-60 parts, rattletop 10-30 parts, great burdock achene (stir-fry) 40-110 parts and auxiliary material are prepared.

The medicine of aforementioned therapies fever in children infantile convulsion, is calculated in parts by weight, mainly by 25 parts of the coptis, PULVIS CORNUS BUBALI CONCEN TRATUS 50 parts, 25 parts of cornu caprae hircus, 25 parts of calamitas urinae hominis's (forging), 25 parts of Fermented Soybean, 50 parts of folium isatidis, 50 parts of schizonepeta, 50 parts of notopterygium root, the root of kudzu vine 50 parts, 50 parts of glutinous rehmannia, 50 parts of caulis clematidis armandii, 50 parts of the radix paeoniae rubrathe, 50 parts of radix scutellariae, 75 parts of the root of purple-flowered peucedanum, 75 parts of radix scrophulariae, 75 parts of balloonflower root, radix bupleuri 37.5 parts, 37.5 parts of Chinese tamarisk tops, 20 parts of rattletop, 75 parts of great burdock achene (stir-fry) be prepared.

A kind of preparation method of the medicine of aforementioned therapies fever in children infantile convulsion, takes said medicine, conventionally carries out Extraction, is combined with conventional pharmaceutical adjuvants, can also be not added with auxiliary material, traditional drug formulations are made.

In the preparation method of the medicine of aforementioned therapies fever in children infantile convulsion, the pharmaceutical preparation is oral formulations.

In the preparation method of the medicine of aforementioned therapies fever in children infantile convulsion, the oral formulations include pill, granule, piece Agent or capsule.

In the preparation method of the medicine of aforementioned therapies fever in children infantile convulsion, the pill is prepared：Cornu caprae hircus is taken to crush Mixed into fine powder and PULVIS CORNUS BUBALI CONCEN TRATUS, it is standby；Remaining medicinal material respectively takes 2/3 amount to be ground into fine powder, sieving, and fine powder is standby；Coarse powder Cream is carried with remaining medicinal material boiling, cream mixes general ball with above-mentioned powder, dries, and coating, produces.

In the preparation method of the medicine of aforementioned therapies fever in children infantile convulsion, the granule is prepared：Take cornu caprae hircus powder It is broken into fine powder to mix with PULVIS CORNUS BUBALI CONCEN TRATUS, obtains mixed powder, it is standby；Remaining medicinal material boiling proposes cream, cream and above-mentioned mixed powder and leaching The cane sugar powder of cream amount 20% and 20% dextrin mixing granulation, dry, produce.

In the preparation method of the medicine of aforementioned therapies fever in children infantile convulsion, the tablet is prepared：Cornu caprae hircus is taken to crush Mixed into fine powder and PULVIS CORNUS BUBALI CONCEN TRATUS, obtain mixed powder, it is standby；Remaining medicinal material boiling carries cream, cream and above-mentioned mixed powder and medicinal extract The starch of amount 20% mixes, and tabletting, film coating, produces.

In the preparation method of the medicine of aforementioned therapies fever in children infantile convulsion, the capsule is prepared：Take cornu caprae hircus powder It is broken into fine powder to mix with PULVIS CORNUS BUBALI CONCEN TRATUS, obtains mixed powder, it is standby；Remaining medicinal material is extracted with 70% alcohol reflux, extract solution Recovery ethanol is simultaneously condensed into medicinal extract, and medicinal extract and the starch and 0.6% magnesium stearate of above-mentioned mixed powder and medicinal extract amount 20% mix, With 60% alcohol granulation, dry, filling, produce.

Medicine of the present invention is mainly by the coptis, PULVIS CORNUS BUBALI CONCEN TRATUS, cornu caprae hircus, calamitas urinae hominis, Fermented Soybean, folium isatidis, chaste tree Mustard, notopterygium root, the root of kudzu vine, glutinous rehmannia, caulis clematidis armandii, the radix paeoniae rubrathe, radix scutellariae, the root of purple-flowered peucedanum, radix scrophulariae, balloonflower root, radix bupleuri, Chinese tamarisk tops, rattletop and great burdock achene system It is standby to form.Wherein, coptis energy heat-clearing and damp-drying drug, purging intense heat and detonicating.The coptis also has antibacterial, antimycotic, antiviral, anti-amoeba, resists Scorching, anti diar rhea, refrigeration function is hypoglycemic, and reducing blood lipid is anti-oxidant, antiulcer action.For damp and hot feeling of fullness, acid regurgitation is vomitted, is rushed down Dysentery, jaundice, unconsciousness due to high fever, heart-fire hyperactivity, dysphoria and insomnia, blood-head tells nosebleed, hot eyes, toothache, quench one's thirst, carbuncle swells furunculosis；Eczema is controlled outside, Wet sore, duct are suppurated.It is burning hot that prepared RHIZOMA COPTIDIS with vino is apt to the clear part of the body cavity above the diaphragm housing the heart and lungs.Also it is used for hot eyes, aphtha.Prepared RHIZOMA COPTIDIS with rhizoma zingiberis recens juice clearing stomach anti-vomiting.It is additionally operable to tremble with fear Hot mutually knot, damp and hot middle resistance, feeling of fullness vomiting.And the easypro liver anti-vomiting of cornel coptis.For liver-stomach disharmony, acid regurgitation is vomitted.Cornu bubali is dense Contracting powder is applied to the symptoms such as pruigo, epilepsy, hyperpyretic convulsion, mainly there is cardiac stimulant, anti-inflammatory, anti-infective, calm, relieving convulsion, shortening bleeding Time, reduce the effect such as capillary permeability, excited Pituitary Adrenalcortical system.The ether of cornu bubali or 95% ethanol Extract has sedation to rat.Cornu bubali decoction plays the role of substantially to shorten the bleeding time, and its LVFS is 43.24%.To go calcium sheep blood plasma to be tested, cornu bubali finds no the presence for promoting blood coagulation substance in addition to calcic.Continuously give Medicine can reduce capillary permeability in 2-4 weeks.These effects can illustrate that cornu bubali also has the effect of cooling blood and dissolving purpura.Cornu caprae hircus, As cattle and sheep section horn, it is a kind of medicine.Calamitas urinae hominis is the thin slice for condensing in wooden pail for urine or urinating the canescence amorphism in cylinder Or block piece, clean dry form.For abscess of throat, or the disease such as noma aphtha, the coptis, golden cypress, catechu, indigo naturalis, ice can be coordinated The medicines such as piece, borax, grind external application.To diseases such as the spitting of blood caused by blood-head, bleeding from five sense organs or subcutaneous tissues, cacumen biotae, setose thistle, field thistle, rhizoma nelumbinis can be coordinated The blood-cooling hemostatics such as charcoal are the same as use.《Detailed outline》Say：Calamitas urinae hominis, drop mutually fire, dispersing blood stasis blood, cover it is salty can mild laxation walk blood therefore.Moderns' disease mouth The all sores of tongue, with it effectively, fall fire is tested.... fall fire dispersing blood stasis blood, control throat ability to speak life sore, infantile malnutrition due to digestive disturbances or intestinalparasites NI, the bleeding from orifices of the head, skin Sweat blood.《Bencao Jingshu》Say：Drown white Yin, and its taste is salty, and gas is cool, nontoxic, the fire that energy purging the liver of pathogenic fire, kidney, three Jiao, bladder are had a surplus.Fermented Soybean Pungent scattered hardship is let out cold in nature, enters lung channel, has the saturating property of evacuation a surname, can dissipate table heresy thoroughly, and hot and suffocating with energy surname dissipate, and the power of sweating is rather Steadily, having sweating, impairment of yin is not said.《Mingyi Bielu》Say：" main cold headache fever and chills, miasma are vicious." it is conventional control diseases caused by external factors from the beginning of, Symptoms include fever with aversion to cold, lossless, the card such as headache nasal obstruction.《Haigoushen》Carry：" controlling bloody flux stomachache ".And《Fan Wangfang》Fermented soya beans, salted or other wise Chinese onion soup, then use This crystalline substance cures the wound cold sudden and violent lower and stagnant dysentery stomachache.Therefore this product has the effect of clearing away heat to cure dysentery.If symptoms include times of defecation increases and measures few, abdomen Bitterly, it is tenesmus, lower mucus and sanguinopurulent stool.This is the outer gas by epidemic disease caused by damp-heat pathogen poison, and internal injury diet raw food, stagnate the institute in intestines Cause.This product clearing away heat to cure dysentery can be used.Folium isatidis be Verbenaceae yellow avens, few section plant indigo plant, cruciferae isatis, The leaf or branches and leaves of careless smalt or acanthaceous vegetable acanthaceous indigo etc..Main product Jiangsu, Anhui, Hebei, Henan, zhejiang and other places.Taste bitter and cold. Function：Clearing heat and detoxicating, cooling blood and hemostasis, ecchymose removing.It is main fever caused by exogenous pathogenic factors excess heat polydipsia, abscess of throat, aphtha, jaundice, pyrotoxic dysentery, acute Enteritis, swollen ulcer drug, bleeding from five sense organs or subcutaneous tissue, blood strangury, traumatism and bleeding.Schizonepeta is labiate, enters medicinal its and dries cauline leaf and flower spike.It is fresh and tender Bud children are calm optimal, balm leaf yellow green, the square micro-strip purple of stem, cross section yellow-white, the slightly black purple yellow green of tassel.Taste Flat, warm-natured, nontoxic, faint scent is dense.Schizonepeta is sweating, alexipyretic, is one of conventional herbal medicine of China.Can town phlegm, timid wind, cool blood. Control influenza, headache fever and chills sweating, vomiting.Notopterygium root, warm-natured, dispellieg cold and dampness, for lossless, cold-dampness numbness of catching cold, have a headache, Limb rheumatalgia pain.Can inducing sweat and dispelling exogenous evils, again can wind-damp dispelling and relieve pain, but when as diaphoretic for the treatment of colds and influenza, its wind-dispelling should be stopped Pain effect is intimately associated, that is, when being used clinically for chill table disease, it is necessary to is had the diseases such as headache or arthralgia concurrently, is just considered Use.As for arthralgia pain due to rheumatism is controlled, either with or without table disease, can all apply.According to clinical practical experiences, the effect of product are brought down a fever, is very It is good, the antipyretic such as product such as dandelion, Radix Isatidis can be coordinated to control wind-heat table disease, and also it is existing without heating once again typically after heat is moved back As.The root of kudzu vine is the health products that people commonly use, and is brought down a fever with expelling pathogenic factors from muscles and skin, is promoted the production of body fluid to quench thirst, promoting eruption, Shengyang Zhixie, clearing and activating the channels and collaterals effect. People are frequently as relieving summer-heat, the drink to relieve the effect of alcohol.Fever caused by exogenous pathogens headache is can also be used for, stiff nape and back is thirsty, quenches one's thirst, measles without adequate eruption, heat Dysentery, diarrhea, dizziness and headache, hemiplegia, chest impediment and cardialgia, during wine poison is hindered.Pharmacological research shows that the root of kudzu vine is reduced blood pressure, slowed down Heart rate, myocardial oxygen consumption is reduced, expand coronary vasodilator, improved normal and ischemic myocardium metabolism, improve Brain circlulation, peripheral vessels And microcirculation, anti-arrhythmia is reducing blood sugar and blood fat, anti-oxidant, antitumor, always Platelet, improves immunity and note Recall the pharmacological actions such as power.There is glutinous rehmannia clearing heat and cooling blood effect to enter ying blood for warm heat disease heat, high fever coma, and dry tongue is deep red.As clearly Seek soup.The convalescent stage of febrile disease is controlled, waste heat not to the greatest extent, hindered, night fever abating at dawn, the red rapid pulse person of tongue, such as Qinghao Biejia Tang by yin-fluid.Available for controlling temperature Pyreticosis heat enters ying blood, blood-heat and toxin exuberance, hematemesis and epistaxis, atropurpureus macula.Caulis clematidis armandii has inducing diuresis for treating strangurtia, and relieving restlessness that clears away heart-fire, stimulate the menstrual flow lower breast, For stranguria, oedema, red, the aphthae of vexed urine, Amenorrhea breast is few, damp and hot numbness pain.The radix paeoniae rubrathe is famous wild genuine Chinese medicine, tool There is the effect of clearing heat and cooling blood, blood stasis removing analgesic.For thermal man's ying blood, febrile virulent maculae, hematemesis and epistaxis, red eye, swell pain, liver-depressed hypochondrium pain, warp Close dysmenorrhoea, addiction lump in the abdomen stomachache, injury from falling down, carbuncle swells sore.It is radix scutellariae bitter, cold in nature, there is heat-clearing and damp-drying drug, purging intense heat and detonicating, hemostasis, antiabortive And other effects.Cure mainly warm heat disease, the infection of the upper respiratory tract, cough with lung heat, neonatal jaundice caused by dampness-heat, pneumonia, dysentery, hemoptysis, hot eyes, movement of the foetus not The diseases such as peace, hypertension, carbuncle swells furuncle sore.Root of purple-flowered peucedanum hyoscine, it is conventional Chinese medicine.Can antipyretic, eliminating the phlegm, cure cold cough, bronchitis And furuncle.Cure mainly dispelling wind-heat, lower gas, dissolving phlegm.Headache due to pathogenic wind-heat is controlled, the hot cough and asthma of phlegm, is vomitted inverse, chest diaphragm is full vexed.Radix scrophulariae has heat-clearing Cool blood；Nourishing Yin and falling fire；The effect of detoxicating and resolving a mass.Main warm heat disease heat and ying blood；Body heat；Polydipsia；Tongue is deep red, sends out spot, and hectic fever due to yin labor is coughed is empty Tired not awake, Tianjin hinder constipation, mesh is puckery dim-sighted, the swelling and pain of throat larynx, scrofula subcutaneous nodule, skin sore.Balloonflower root is Campanulaceae balloonflower root platymiscium, It is grown in China, the Korea peninsula, Japan and eastern Siberia.Root can be used as medicine, and can also pickle into salted vegetables, in Northeast Area of China Referred to as " stone of a dog's gallbladder, kidney or bladder " salted vegetables.With facilitaing lung, eliminating the phlegm, relieving sore-throat, apocenosis, relieving the five internal organs, fill blood, mend the exhaustion or lesion of the five internal organs, foster the spirit of nobility the effect of.Can be effective Treat coughing with a lot of sputum, abscess of throat, lung carbuncle pyemesis, fullness in the chest and hypochondriac pain, dysentery stomachache, aphthae, red eye, swell pain, uroschesis. Radix bupleuri is《Chinese Pharmacopoeia》The herbal medicine included, medicinal part are the dry root of umbelliferae bupleurum or radix bupleuri scorzoneraefolii.There is reconciliation In table, the effect of soothing the liver rising Yang.Taken off for cold, fever, fevers and chills alternate, malaria, stagnation of QI due to depression of the liver, sternal rib pain, prolapse of the anus, uterus Hang down, irregular menstruation.Chinese tamarisk tops spray and Ye Ke are used as medicine, and flat property and sweet taste is salty, can saturating having a heatstroke rash.Major function：Deliver promoting eruption, solution Poison, diuresis, wind-damp dispelling.Rattletop gas is micro-, mildly bitter flavor and it is puckery.The medicine of rattletop one, mainly have liter and to lift hair thoroughly, it is clearing heat and detoxicating and deliver promoting eruption And other effects.Gas plague when can effectively treat, fever and chills of having a headache, laryngalgia, aphtha, macula are impermeable；The sinking of qi of middle-jiao, protracted dysentery and diarrhea, prolapse of the anus, Women is collapsed, band, uterus tenesmus；Carbuncle sore tumefacting virus.Great burdock achene has dispelling wind and heat from the body, facilitaing lung promoting eruption, relieving sore-throat dissipating bind, the work(of removing toxicity for detumescence Effect.Belong to wind-heat-dispersing medicinal in diaphoretic medicine.Modern study, great burdock achene can also be used to prevent and treat diabetic nephropathy；Arctium lappa fruit contains ox Arctigenin of the burdock glucoside through hydrolysis generation has active anticancer.

Said medicine prescription, play altogether it is clearing heat and detoxicating, the effect of saturating table slit phlegm.For acute infantile convulsion, typhoid fever heating, face night hair Burn, urine band blood, dimly visible do not go out of measles and cause body heat cough；Dysentery characterized by blood in the stool, watery diarrhea, dyspepsia, stomachache.It is evident in efficacy, Small side effects.

Applicant carried out following experiments, the provable present invention has effective effect；

The pharmacodynamics test of experimental example 1

1 experiment material

1.1 medicine

Medicine (being prepared as described in Example 1) of the present invention, positive drug：Children's return of spring ball, it is auspicious by Kweiyang Dechang Pharmaceutcal corporation, Ltd provides, lot number：20140116.

Usage and dosage：Warm water is ground clothes or taken, and below one full year of life 1 tablet each time, 1-2 year is 2 tablets each time, and 3-4 year is 3 tablets each time, 5-7 year 5 tablets each time, 2-3 times on the one.Specification：0.18 gram is weighed per ball.

Dosage is set：Orally, the 0.36-0.54g of day dose below one full year of life, 1-2 year day dose 0.72-1.08g, 3-4 Day dose 1.08-1.62g in year, 5-7 year day dose 1.8-2.7g.

With 1-3 year, day dose 1.08g is counted for this research, and body weight is calculated by 3 × 2+8=14kg, i.e. the daily dosage of children For 0.077g/kg.

Mouse weight 12-14g, rat body weight 40-60g.Effect experiment pill, this paper dosage are represented again with ball.

1.2 animal

Kunming mouse, male and female dual-purpose, body weight 12-14g, SD rat, male and female dual-purpose, body weight 40-60g, by Chongqing City Medicine research institute institute of lab animals's (credit number：SCXK (Chongqing) 2012-0006) and medical university of the army of the Chinese People's Liberation Army Learn Experimental Animal Center (credit number：SCXK- (army) 2012-0003) provide.

1.3 reagent

Glacial acetic acid, Chengdu Ke Long chemical reagents factory, lot number：20120803；Dimethylbenzene, Tianjin great Mao chemical reagent Factory, lot number：20080921；Chloraldurate, Beijing chemical reagents corporation, lot number：20100218；Nikethamide Injection, Shanghai The rich pharmacy of standing grain, lot number：1308061；Aluzyme, Yantai City Shen En Food Co., Ltd, lot number：20140223；Ammoniacal liquor, Beijing Chemical Plant, lot number：20120814；Phenol red, Tianjin Jin Bei Fine Chemical Co., Ltd, lot number：20121107；OK a karaoke club Glue, Henan Tian Xing food additives Co., Ltd, lot number：20110923.

1.4 zoopery places

Guiyang College of Traditional Chinese Medicine's pharmacological toxicology laboratory, well-ventilated, sanitation and hygiene, 20-25 DEG C of temperature, humidity 55%- 65%.The other sub-cage rearing of animal unisexuality, free water feed.

1.5 key instrument

JM-B type electronic balances, Yuyao City discipline inscription are weighed calibration equipment Co., Ltd；ALC-210.3 type electronic balances, on Current chart level instruments and meters Co., Ltd；Table model high speed centrifuge, Anting Scientific Instrument Factory, Shanghai；721 spectrophotometers, upper Nereid Close instrument and meter Co., Ltd；Atomizer, Yuyue Medical Apparatus Co., Ltd., Jiangsu；ZZ-6 type mouse autonomic activities instrument, Chengdu Tai Meng Science and Technology Ltd.s；RB-200 intelligence hot-plate instruments, Shanghai benefit connection science and education equipment Co., Ltd.

1.6 statistical procedures

Data are represented with x ± S, and statistical procedures, multigroup measurement data are carried out using the statistical analysis softwares of SPSS 17.0 And compare two-by-two using one-way analysis of variance, P<0.05 is statistically significant.

2 experimental methods and result

2.1 the experimental study of cough-suppressing phlegm-dispelling functions

2.1.1 the influence of cough mouse is drawn to ammoniacal liquor

Kunming mouse 70, male and female half and half, body weight 12-14g are randomly divided into 5 groups, i.e. blank control group, the present invention is high, In, low dose group, positive drug children's return of spring ball group, every group 14, gastric infusion, 0.2ml/10g, once a day, continuously give Medicine 5 times.

The laggard whereabouts cough experiments of last dose 1h.From the bottomless plastic casing that specification is 22cm × 16cm × 10cm as mist Change cover, first add 2ml ammoniacal liquor (needing to change every time) atomization 30s during experiment in atomizer, make the ammoniacal liquor of atomization full of atomization Cover, mouse is put into atomized cover, observes and records mouse cough incubation period and cough time in 5min from being put into atomized cover respectively Number.It the results are shown in Table 1.

Table 1 ammoniacal liquor is drawn cough mouse influence (N=14)

Note：Respectively it is administered compared with blank control group, * p<0.05**p<0.01.

As seen from Table 1, compared with blank control group, the mouse cough that each administration group can significantly extend ammoniacal liquor induction is dived Fu Qi, reduce cough number (p<0.05, p<0.01), show medicine of the present invention can suppress ammoniacal liquor induction mouse cough it is anti- Penetrate, mitigate cough symptom, there is obvious antitussive action, its effect is suitable with children's return of spring ball.

2.1.2 to the influence of mouse tracheae section phenols contents

Kunming mouse 70, male and female half and half, body weight 12-14g, it is randomly divided into 5 groups, i.e. blank control group, medicine of the present invention The high, medium and low dosage group of thing, positive drug children's return of spring ball group, every group 14, gastric infusion, 0.2ml/10g, once a day, even It is continuous to be administered 5 times.

Every mouse nape part is engraved on after last dose 0.6% phenol red solution, 0.2ml/10g is subcutaneously injected.Will after 1h Mouse takes off cervical vertebra and put to death, and after back of the body position is fixed, cuts skin along neck median line, exposure tracheae, tracheae is ligatured under annular cartilage, Tracheae and lung tissue are taken out, 3ml 5%NaHCO are placed in after cleaning bloodstain completely in physiological saline₃In solution, shred tracheae with Lung tissue, 30min is soaked, 2000r/min centrifugation 20min, colorimetric at supernatant 560nm is taken, calculates phenol red content in flushing liquor.

The drafting of phenol red standard curve：

Phenol red 0.1g, which is weighed, with assay balance standard is dissolved in 5%NaHCO₃To 100ml in solution, every milli is sequentially diluted to Rise containing phenol red 6 μ g, 5 μ g, 4 μ g, 3 μ g, 2 μ g, 1 μ g.Measure wavelength is 560nm, with spectrophotometer measurement OD values.Contained with phenol red It is abscissa to measure as ordinate, OD values, obtains phenol red standard curve and regression equation.

Each sample OD values surveyed are substituted into equation, the phenol red concentration of each sample is obtained, compare between group.It the results are shown in Table 2.

Table 2 to mouse tracheae phenols contents influence (N=14)

Note：Respectively it is administered compared with blank control group, * p<0.05**p<0.01.、

As seen from Table 2, compared with blank control group, the gas of medicine ball high dose group of the present invention and children return of spring ball group mouse Pipeline section phenols contents are significantly increased (p<0.05, p<0.01), show that medicine of the present invention can promote the phenol red row of tracheae Secrete, there are obvious phlegm-dispelling functions.

The experimental study of 2.2 antipyretic anticonvulsant actions

2.2.1 to the refrigeration function of ferment mother z pyrogenicity rat

SD rats 60, male and female half and half, body weight 40-60g are randomly divided into 5 groups, i.e. blank control group, medicine of the present invention is high, In, low dose group, positive drug children's return of spring ball group, every group 12, gastric infusion, 1ml/100g, once a day, successive administration 5 times.After last dose, the yeast suspension 0.6ml/100g of dorsal sc injection 15%, determines and records injection yeast immediately 0 after suspension, 4,6,8h rat anus temperature.The anus temperature determined of 0h after injection yeast suspension is designated as basic anus temperature, injects ferment 4 after female suspension, 6,8h measure anus temperature be individually subtracted basic anus temperature be different time points temperature approach, progress statistics at Reason.It the results are shown in Table 3.

Table 3 to the refrigeration function of yeast pyrogenicity rat (N=12)

Note：Each administration group is compared with blank control group, * p<0.05**p<0.01.

As seen from Table 3, compared with blank control group, each administration group different time points can reduce rat anus temperature temperature approach, Medicine of the present invention is high, middle dose group is in the most obvious (p of 6,8h coolings<0.05), medicine low dose group of the present invention cools most in 4,8h Substantially (p<0.05, p<0.01), show that medicine of the present invention has certain refrigeration function.

2.2.2 the effect that heat resistance is fainted from fear

SD rats 70, male and female half and half, body weight 40-60g are randomly divided into 5 groups, i.e. blank control group, medicine of the present invention is high, In, low dose group, positive drug children's return of spring ball group, every group 14, gastric infusion, 1ml/100g, once a day, successive administration 5 times.

Rat anus temperature is measured after last dose 1h, febrile convulsion breaking-out is then induced and (rat is placed in 46 ± 0.5 DEG C of hot water Induce febrile convulsion breaking-out in bath, the depth of water by rat stood along beaker when only expose head and be defined, can be worn when every rat enters water Rubber gloves are pressed in water, are treated that its whole body fur drenches, are loosed one's grip when can be stood along beaker, are fainted from fear and are departed from water immediately after occurring Bath.This experiment is tetanic or generalized tonic-clonic is convulsive attack using rat body.).Observation each group rat is fainted from fear incubation period (from luring Fall into convulsions to the time of convulsive attack, most long observation 5min, 5min do not show convulsive attack, are calculated as 5min), duration of status convulsion, Induce anus temperature when terminating rear 2min.The anus temperature rate of climb=(anus temperature when anus temperature-induction starts when induction terminates rear 2min) ÷ Faint from fear incubation period.It the results are shown in Table 4.

Table 4 to febrile convulsion rat influence (N=14)

As seen from Table 4, compared with blank control group, each administration group can significantly extend rat and faint from fear incubation period, shorten Duration of status convulsion, slow down the anus temperature rate of climb (p<0.05, p<0.01), show that medicine of the present invention has necessarily antipyretic anti-frightened The effect of fainting.

2.2.3 anti-nikethamidum causes the effect of mice convulsion

Kunming mouse 70, male and female half and half, body weight 12-14g are randomly divided into 5 groups, i.e. blank control group, the present invention is high, In, low dose group, positive drug children's return of spring ball group, every group 14, gastric infusion, 0.2ml/10g, once a day, continuously give Medicine 5 times.Nikethamidum 0.75g/kg is subcutaneously injected in last dose 1h, each group animal, observes and records each group mice convulsion immediately Surviving animals number in incubation period and 24h.It the results are shown in Table 5.

Table 5 to nikethamidum cause mice convulsion influence (N=14)

Note：Each administration group is compared with blank control group, * p<0.05.

As seen from Table 5, compared with blank control group, each administration group can extend mice convulsion incubation period, wherein with this hair Bright medicine high dose group effect significantly (p<0.05), and the survival rate of mouse is up to 64.3%, shows that medicine of the present invention can To resist the convulsions caused by central stimulant nikethamidum, there is obvious anticonvulsant action.

The experimental study of 2.3 anti-diarrhea effects

2.3.1 to the influence of mouse small intestine advancing movement

Small intestine advance activity experiment is carried out after last dose 1h.The equal charcoal end physiological saline 0.6ml of gavage 10% of every mouse, Cervical vertebra is taken off after 20min and puts to death mouse, cuts open the belly and takes stomach-small intestine-caecum, it is overall to take out, it is not added with traction and is laid on smooth blank, The distance from pyloric sphincter to charcoal end front end (charcoal end advance distance) and to caecum front end (small intestinal length) is measured respectively.Calculate Intestinal propulsive rate.It the results are shown in Table 6.

Intestinal propulsive rate (%)=charcoal end advance distance ÷ small intestinal length × 100%

Table 6 to mouse small intestine advancing movement influence (N=14)

As seen from Table 6, compared with blank control group, each administration group can significantly reduce mouse small intestine propulsion rate (p< 0.05, p<0.01), show that medicine of the present invention can slow down the propulsion of mouse small intestine, the work with certain suppression gastrointestinal motility With its effect is suitable with children's return of spring ball.

2.3.2 to the influence of rhubarb induced mice diarrhoea

Kunming mouse 84, male and female half and half, body weight 12-14g, it is randomly divided into 6 groups, i.e. blank control group, model group, sheet The high, medium and low dosage group of invention medicine, positive drug children's return of spring ball group, every group 14, gastric infusion, 0.2ml/10g, daily Once, successive administration 5 times.

After last dose 1h, in addition to blank control group, remaining each group mouse is respectively with 100% rhubarb charcoal end suspension (rhubarb powder 100g is taken, adds 10% charcoal end physiological saline submergence, is filtered after cold soaking 24h, 40 DEG C of water-baths are condensed into 1g/ml, low temperature Preserve, used time water-bath is heated up to 25 DEG C) 0.6ml gavages, the charcoal end physiological saline 0.6ml of blank control group gavage 10%.With charcoal end For indicator, record mouse arranges time of melena, character, number first, Continuous Observation 6h defecation situation, calculates stool in mice Character integrates.(stool in mice character ranking criterion：0 point, excrement is granular, black, matter are hard, flexible；1 point, excrement is granular, color It is pale brown, matter is soft；2 points, excrement pasty state, color are pale brown；3 points, excrement water sample, color are yellow.) routinely give in experimentation mouse drinking-water and Feed, the accuracy of guarantee test result.It the results are shown in Table 7.

Influence that table 7 is suffered from diarrhoea to rhubarb induced mice (N=14)

Note：Respectively it is administered compared with model group, * p<0.05**p<0.01.

As seen from Table 7, mouse can be rapidly resulted in rhubarb infusion gavage mouse to suffer from diarrhoea, excrement is in water sample, abdomen Rush down number showed increased.Each administration group can significantly extend the time of mouse defecation first, reduce diarrhoea number, alleviating diarrhoea Degree, excrement is set to tend to pasty state or soft granular (p<0.05, p<0.01), show that medicine of the present invention can suppress rhubarb infusion Diarrhea of mouse caused by gavage, diarrhoea number and diarrhoea degree are reduced, there is obvious anti-diarrhea effect, it is acted on rejuvenates with children Ball is suitable.

2.4 sedation and analgesia anti-inflammatory experimental studies

2.4.1 to the influence of mouse autonomic activities

Kunming mouse 70, male and female half and half, body weight 12-14g, it is randomly divided into 5 groups, i.e. blank control group, medicine of the present invention The high, medium and low dosage group of thing, positive drug children's return of spring ball group, every group 14, gastric infusion, 0.2ml/10g, once a day, even It is continuous to be administered 5 times.Last dose 1h, mouse is put into ZZ-6 type mouse autonomic activities instrument, adapts to environment 2min, then continuous note Record mouse autonomic activities number in 5min.It the results are shown in Table 8.

Table 8 to mouse autonomic activities influence (N=14)

As seen from Table 8, compared with blank control group, each administration group can reduce creep number and the standing number of mouse, Wherein with high dose group of the present invention effect significantly (p<0.05), show that medicine of the present invention can reduce the autonomous work of mouse It is dynamic, there is certain sedation.

2.4.2 the influence (hot plate method) of mice pain is caused to thermostimulation

Screen qualified female mice：Hot-plate instrument temperature is 55 ± 0.5 DEG C, and by pain threshold, (mouse licks metapedes in hot plate Time " second ") it is less than 5 seconds and mouse more than 30 seconds removes, remaining qualified mouse (pain threshold is between the 5-30 seconds) is included Formal experiment in next step.70 qualified mouse are selected, body weight 12-14g, are randomly divided into 5 groups, i.e. blank control group, the present invention The high, medium and low dosage group of medicine, positive drug children's return of spring ball group, every group 14, gastric infusion, 0.2ml/10g, once a day, Successive administration 5 times.30min, 90min, 150min determine the pain threshold of each group animal respectively after last dose, and observation medicine is to dynamic The influence of thing pain threshold.It the results are shown in Table 9.

Table 9 to hot plate stimulate mouse pain threshold influence (N=14)

As seen from Table 9, before medicine each group animal pain threshold there are no significant difference, except children's return of spring ball positive drug exists after medicine Show significantly to extend outside the effect of mouse pain threshold during 30min after medicine, remaining each administration group is showed no obvious increase mouse The effect of pain threshold, show that of the present invention group causes mice pain to thermostimulation without obvious inhibiting effect.

2.4.3 Dichlorodiphenyl Acetate causes the influence (writhing method) of mouse writhing reaction

Kunming mouse 70, male and female half and half, body weight 12-14g, it is randomly divided into 5 groups, i.e. blank control group, medicine of the present invention The high, medium and low dosage group of thing, positive drug children's return of spring ball group, every group 14, gastric infusion, 0.2ml/10g, once a day, even It is continuous to be administered 5 times.Last dose 1h, each mouse are injected intraperitoneally 0.6% acetum 0.2ml/ only, observe immediately and record animal Writhing response number (secondary) in 15min, and calculate writhing and suppress percentage.It the results are shown in Table 10.

Inhibiting rate (%)=(the average writhing number of the average writhing number-administration group of blank control group) ÷ blank control groups are averagely turned round Body number × 100%

Influence that table 10 is reacted mouse writhing (N=14)

As seen from Table 10, compared with blank control group, each administration group can significantly decrease acetic acid induced mice writhing Reaction times (p<0.05), show that medicine of the present invention has certain analgesic activity, its effect is suitable with children's return of spring ball.

2.4.4 paraxylene causes the influence of mice auricle swelling

Kunming mouse 70, male and female half and half, body weight 12-14g, it is randomly divided into 5 groups, i.e. blank control group, medicine of the present invention The high, medium and low dosage group of thing, positive drug children's return of spring ball group, every group 14, gastric infusion, 0.2ml/10g, once a day, even It is continuous to be administered 5 times.Last dose 1h, the left ear two sides of mouse is only uniformly applied to dimethylbenzene stoste 0.03ml/, after 40min, place The ear of dead animal, rapid clip or so two, beaten with diameter 8mm card punch in same area and take left and right ear auricle, precise weighing, with The difference of left and right ear auricle weight is mice ear degree, carries out statistical procedures.It the results are shown in Table 11.

Inhibiting rate (%)=(blank control group ear swelling degree-administration group ear swelling degree) ÷ blank control group ear swellings degree × 100%

As seen from Table 11, compared with blank control group, each administration group can significantly mitigate dimethylbenzene induced mice auricle Swelling (p<0.05, p<0.01), wherein the most obvious with medicine high dose group of the present invention effect, its swelling inhibiting rate is 44.2%, show that medicine of the present invention has the function that certain redness for suppressing acute inflammation, can eliminating acute inflammation rapidly The symptoms such as hot pain.

The paraxylene induced mice auricle edema of table 11 influence (N=14)

2.4.5 the influence of rat paw edema caused by Carrageenan

SD rats 60, male and female half and half, body weight 40-60g are randomly divided into 5 groups, i.e. blank control group, medicine of the present invention is high, In, low dose group, positive drug children's return of spring ball group, every group 12, gastric infusion, 1ml/100g, once a day, successive administration 5 times.

Last dose 1h, 1 after Rat Right rear foot foot plantar intracutaneous injection 1% carrageenan 0.1ml, Yu Zhiyan, 2,4h With vernier caliper measurement vola pedis thickness, and the thickness of left foot corresponding site is measured, calculate swelling rate.It the results are shown in Table 12.

Swelling rate (%)=(right crus of diaphragm vola pedis thickness-left foot vola pedis thickness)/left foot vola pedis thickness × 100%

Rat paw edema caused by the Carrageenan of table 12 influence (N=12)

As seen from Table 12, compared with blank control group, each dosage group of medicine of the present invention can substantially subtract at multiple time points The paw swelling of light rat, wherein with medicine high dose group of the present invention effect (p the most obvious<0.05, p<0.01), it eliminates anxious Sustainable more than the 4h of effect of property inflammation swelling, shows that medicine of the present invention has the function that certain anti-inflammation.

2.4.6 to the influence of swollen hyperplasia of rat granuloma

Take SD rats, male and female half and half, body weight 40-60g.Rat is under chloraldurate (300mg/kg) anesthesia, in chest just It is middle to make an opening, peeled off with haemostatic clamp at skin to armpit, in advance at autoclaved 30mg cotton balls implantation armpit, skin will be sutured Skin, administration is grouped after animal is clear-headed.

The rat of successful surgery is randomly divided into 5 groups, i.e. blank control group, the high, medium and low dosage group of medicine of the present invention, sun Property medicine children's return of spring ball group, every group 12, gastric infusion, 1ml/100g, once a day, successive administration 14 times.Last dose 1h afterwards, take off cervical vertebra and put to death animal, open skin of chest, carefully peel off cotton balls and granulation tissue, be placed on electronic balance and weigh, i.e., For cotton balls granulation weight in wet base.Cotton balls granulation is placed in 60 DEG C of baking ovens, dried 24 hours, takes out and weighs as cotton balls granulation dry weight. It is that the how many index of granulation carries out statistical procedures to subtract cotton balls recast with cotton balls granulation weight in wet base, dry weight respectively.It the results are shown in Table 13.

Table 13 to swollen hyperplasia of rat granuloma influence (N=12)

As seen from Table 13, compared with blank control group, each administration group can significantly suppress rat granuloma, mitigate meat Bud weight in wet base or dry weight (p<0.05, p<0.01) it is, wherein the most obvious with medicine high dose group of the present invention effect, show medicine of the present invention Thing can suppress granulation hyperplasia, have the function that certain anti-chronic inflammation, and its effect is suitable with children's return of spring ball.

Pass through above-mentioned experimental study, the results showed that：

(1) medicine of the present invention has cough-suppressing phlegm-dispelling functions：Ammoniacal liquor can be extended to draw cough mouse cough incubation period and reduce cough Number, and increase mouse tracheae phenols contents.

(2) medicine of the present invention has antipyretic anticonvulsant action：Rat fever caused by yeast can be reduced, make different time points big The mouse anus temperature difference is decreased obviously；Febrile convulsion rat convulsions incubation period can be extended, shorten duration of status convulsion, and reduce the rising of anus temperature Speed；Nikethamidum mice convulsion incubation period can be extended and promote the survival of mouse.

(3) medicine of the present invention has anti-diarrhea effect：Mouse small intestine propulsion rate can be significantly reduced, extends rhubarb induced mice The defecation time first of diarrhoea, reduce diarrhoea number and alleviating diarrhoea degree, improve fecal character.

(4) medicine of the present invention has sedation and analgesia antiinflammatory action：The autonomic activities number of mouse can be reduced；Acetic acid is reduced to cause Mouse writhing stoichiometric number and the pain threshold for increasing hot plate mouse；Mitigate mice caused by dimethylbenzene xylene auricle swelling degree, suppress carrageenan Rat toes swelling, mitigate granuloma induced by implantation of cotton pellets rat granulation weight in wet base and dry weight.

The long term toxicity test of experimental example 2

1 experiment material

1.1 medicine

Medicine (being prepared by embodiment 1) of the present invention, usage and dosage：Warm water is ground clothes or taken, every time 1 below one full year of life Grain, 1-2 year 2 tablets each time, and 3-4 year 3 tablets each time, and 5-7 year 5 tablets each time, 2-3 times on the one.Specification：0.18 gram is weighed per ball.

With 1-3 year, day dose 1.08g is counted for this research, and body weight is calculated by 3 × 2+8=14kg, i.e., clinical consumption per day is 0.077g/kg。

The suspension oral gavage for facing used time concentration needed for distilled water is configured to is administered.

1.2 animal

SD rats, male and female half and half, 80, body weight 80-100g, by Military Medical Univ No.3, P.L.A experimental animal Center provides, quality certification number：SCXK- (army) 2012-0003.

1.3 key instrument

JY601 type electronic balances, upper current chart level instruments and meters Co., Ltd；OLYMPUS BH-2 microscopes, Japan；SC- 970 Automatic Blood Cell Analyzers, Bei Ken companies of Switzerland；Hitachi's 7170A automatic clinical chemistry analyzers, Kodak of the U.S.；HPIAS- 1000 high-definition color picture and text pathological analysis systems, light microscopic.

1.4 experimental datas count

Experimental data represents that t examines between carrying out group with x ± S.

2 experimental methods

2.1 experiment condition

The front and rear equal unisexuality of rat of administration is fed, free water, room temperature 20 not per 5 group supports of cage with full-valence pellet feed DEG C~25 DEG C, humidity 55%~65%.First adapt to environment before administration to raise several days, observation rat general status, change without exception, Start packet administration again to be tested.

2.2 packets and dosage

SD rats 80, male and female half and half are randomly divided into 4 groups, every group 20, respectively as medicine of the present invention high, medium and low three Individual dosage group and blank control group.Administration group dosage is respectively 4.620g, 2.310g, 1.155g/kg body weight, and administration concentration is distinguished For 23.10%, 11.55%, 5.78%, the daily upper and lower noon is respectively administered once, and as said preparation drafts the daily dosage of clinical children 60 times, 30 times, 15 times of 0.077g/kg body weight.Administration volume is 10ml/kg body weight.

2.3 methods of administration and method

Because being to be administered orally, the equal gastric infusion of each group animal.During daily morning 8-10,4-6 in afternoon when each gavage It is administered once, administration volume is 10ml/kg body weight, continuous 13 weeks；Observation animal general status daily, each group animal is recorded weekly Body weight and food-intake once, increase according to the weight of animals and changed, and adjust dosage.

2.4 the test period

Total cycle is tested as 15 weeks, first 13 weeks are administration time, are discontinued within latter 2 weeks, observe animal different time whether respectively Toxic reaction.Administration phase, in be administered 13 weeks when, after last dose fasting can't help water 12 hours, every group takes 10 animal (male and female Half and half) femoral vein takes blood, measure animal blood cytology, blood biochemical analysis after weighing, while puts to death animal progress system and become celestial, After observation each organs and tissues of animal whether there is the anomalous variations such as hyperemia, enlargement, bleeding, then take each mouse main organs to weigh respectively, count After calculation organ coefficient and other organs and tissues samples are carefully peeled off 10% formaldehyde of immersion such as peripheral adipose tissue and fixed, and carry out pathology Tectology inspection.Withdrawal time, remaining animal drug withdrawal conventinal breeding 2 weeks, general status observation is carried out daily, per journal body weight And food-intake, fasting can't help drink and put to death animal in 12 hours, detect above-mentioned indices.

3 inspection projects

3.1 overview

The mode of appearance sign of daily observation each group animal, behavioral activity, hair luster, feed, drinking-water, stool Deng；It was found that intoxicated animals are isolated immediately, primary part observation；It was found that dead or moribund animals, at once postmortem.Claim the weight of animals weekly, Dosage is adjusted accordingly, while records each group animal feed consumption.

3.2 detection project

3.2.1 blood cytology Index for examination

Leucocyte (WBC), neutrophil leucocyte total (#NEUT), lymphocyte absolute value (#LYMPH), monocyte count (MONO#), acidophil number (#EOS), basocyte number (#BASO), RDW (RDW), neutrophil leucocyte percentage Than (%NEUT), cent lymphocytes (%LYMPH), monocyte percentage (%MONO), acidophil percentage (% EOS), basocyte percentage (%BASO), red blood cell (RBC), hemoglobin (HGB), packed cell volume (HCT), average red Cell volume (MCV), MC Hgb (MCH), erythrocyte mean hemoglobin concentration (MCHC), blood platelet (PLT), Mean Platelet Volume (MPV).

3.2.2 blood biochemical analysis Index for examination

Potassium (K), sodium (Na), chlorine (CL), glucose (GLU), triglycerides (TG), T-CHOL (CHOL), urea nitrogen (BUN), creatinine (CREA), glutamic-pyruvic transaminase (ALT), glutamic-oxalacetic transaminease (AST), alkaline phosphatase (AKP), creatine kinase (CK), total protein (TP), albumin (ALB), globulin (GLB), total bilirubin (TBIL).

3.2.3 major organs tissue specimen

The heart, liver, spleen, lung, kidney, adrenal gland, thymus gland, brain, uterus, ovary, testis, epididymis, weigh respectively, calculate organ Coefficient；Then at the heart, liver, spleen, lung, kidney, adrenal gland, thymus gland, brain tissue, thyroid gland, hypophysis, tracheae, oesophagus, stomach, intestines, bladder, The same position materials of the organs and tissues such as pancreas, lymph node, spinal cord, optic nerve carry out FFPE, section, HE dyeing；Put optics Micro- sem observation and with blank control group carry out internal organs pathological tissue compared with.First comparison check high dose group is moved with blank control group Thing tissue morphology pathological change, middle dose group and the formaldehyde of low dose group animal organ tissue specimen 10% are fixed for future reference.

3.2.4 pathological examination

Perform an autopsy on sb., and main organ and tissue are fixed with 10% formaldehyde, preserved.When each dosage group animal postmortem not It was found that the histopathological examination of high dose group and blank control group animal is only carried out during obvious lesion.Such as find that lesion is right again In, low dose group animal checked accordingly.

3.3 index observing times

The general status of all experimental animals of daily complete observation, animal activity behavior, stool, appearance sign, is raised The material consumption of one week；Weigh weekly once；It was administered for 13 weekends and is discontinued 2 weeks and recovers the end of term, it is each to carry out once above-mentioned project Check comprehensively.

4 experimental results

4.1 pairs of rat ordinary circumstances and the influence of feed

In successive administration 13 weeks and it is discontinued in 2 weeks, by each administration group with blank control group compared with, observes animal activity, OK For, diet, stool, hair luster etc., 4 groups of animal situations are similar, show no obvious abnormalities change.Rat ingests within the same time Measure also no significant difference.It the results are shown in Table 14 and table 15.

14 successive administration of table 13 weeks and the influence to the per day food-intake of female rats (g/) in 2 weeks of being discontinued

Note：Different time points, each administration group is compared with blank control group, P>0.05.

15 successive administration of table 13 weeks and the influence to the per day food-intake of male rat (g/) in 2 weeks of being discontinued

As a result show, every animal daily consumption appetite in gradually increase trend, each administration group compared with blank control group, No significant difference, P ＞ 0.05.Show rat continuous gavage be administered 13 weeks and drug withdrawal 2 weeks, to male and female rat chow day's expenditure without Significantly affect.

The influence of 4.2 pairs of rat body weights

The high, medium and low Three doses of medicine of the present invention are to the body weight and blank control group after rat successive administration different time Compare, its difference the results are shown in Table 16 and table 17 without significant change.

The long-term successive administration of table 16 13 weeks and the influence during being discontinued 2 weeks to female rats body weight (g)

Note：Each administration group is compared with blank control group, P>0.05；It is within 0 week medicine early stage, n=10；It is within 1-13 weeks administration phase, n =10；14-15 weeks withdrawal time, n=5.

The long-term successive administration of table 17 13 weeks and the influence during being discontinued 2 weeks to male rat body weight (g)

Note：Each administration group is compared with blank control group, P>0.05；It is within 0 week medicine early stage, n=10；It is within 1-13 weeks administration phase, n =10；It is within 14-15 weeks withdrawal time, n=5.

As a result show, in the observation period, each group male and female rat body weight gradually increases, and grows good；Each administration group with Compared with period blank control group, each time point body weight no significant difference compared with blank control group, P ＞ 0.05.Show big Mouse continuous gavage is administered 13 weeks and is discontinued 2 weeks, and male and female rat body weight is influenceed without overt toxicity.

4.3 influence on rat blood cytology

It is administered 13 weeks and is discontinued 2 weeks to rat oral gavage with medicine of the present invention, each group animal hematology Indexs measure result is shown in Table 18, and table 19.

Table 18 be administered 13 weeks to rat blood cytology index influence (N=10)

Note：Each administration group animal blood cytology indices numerical value respectively with blank control group corresponding index numeric ratio Compared with P>0.05.

Table 19 be discontinued 2 weeks to rat blood cytology index influence (N=10)

As a result show, the high, medium and low Three doses successive administration of medicine of the present invention 13 weeks and be discontinued 2 weeks, it is thin to the blood of rat Born of the same parents, which have no, to be significantly affected, and is statistically analyzed, P ＞ 0.05.It is therefore contemplated that children's return of spring ball larger dose, long period Administration in (13 weeks) and it is discontinued 2 weeks, to the hematopoiesis function of rat without significant toxic effect.

The biochemical influence of 4.4 pairs of rat bloods

It is administered 13 weeks and is discontinued 2 weeks to rat oral gavage with medicine of the present invention, the biochemical Indexs measure knot of each group animal blood Fruit is shown in Table 20 and table 21.

Table 20 be administered 13 weeks to the biochemical index of rat blood influence (N=10)

Table 21 be discontinued 2 weeks to the biochemical index of rat blood influence (N=10)

As a result show, the high, medium and low Three doses successive administration of medicine of the present invention 13 weeks and be discontinued 2 weeks, to the blood of rat Biochemical indicator, which is showed no, to be significantly affected, every biochemical indicator numerical value such as the liver function of rat and renal function respectively with blank control group Respective value compares, and has no notable difference, P ＞ 0.05；Therefore show medicine larger dose successive administration of the present invention 13 weeks and stop Medicine 2 weeks is to indexs such as Liver Function, renal functions without notable toxic action.

The influence of 4.5 pairs of rat major organs indexes

It is administered 13 weeks and is discontinued 2 weeks to rat oral gavage with medicine of the present invention, system autopsy：Brain, heart, liver, The shape of the internal organs such as spleen, lungs, kidney, adrenal gland, thymus gland, thyroid gland, stomach, intestines, testis, epididymis, prostate, uterus, ovary State, size, color do not find macroscopic change.Each group animal main organs index testing result is shown in Table 22,23,24, 25。

22 successive administration of table 13 weeks to female rats main organs index (g/100g) influence (N=5)

Note:Each each organ index value of administration group animal is respectively compared with exponential quantity corresponding with blank control group, P>0.05.

Table 23 be discontinued 2 weeks to female rats main organs index (g/100g) influence (N=5)

24 successive administration of table 13 weeks to male rat main organs index (g/100g) influence (N=5)

Table 25 be discontinued 2 weeks to male rat main organs index (g/100g) influence (N=5)

As a result show, the high, medium and low Three doses successive administration of medicine of the present invention 13 weeks and be discontinued 2 weeks, it is mainly dirty to rat Device tissue has no obvious toxic effect, and each administration group rat items organ index is compared with blank control group without significance difference It is different, P ＞ 0.05；Therefore show medicine larger dose successive administration of the present invention 13 weeks and be discontinued 2 weeks to each organs and tissues of rat without show Write toxic action.

The influence of 4.6 pairs of rat important organ histoorgan pathomorphisms

To medicine successive administration of the present invention 13 weeks, and high, medium and low the Three doses group and blank control group being discontinued 2 weeks Three batches, kill and take rat and solution cuts the heart, liver, spleen, lung, kidney, adrenal gland, thymus gland, brain, hypophysis, uterus, the ovum of each group rat Nest, testis, epididymis, prostate, thyroid gland, tracheae, oesophagus, stomach, sustainer, duodenum, ileum, colon, bladder, pancreas, The histoorgans such as lymph node, optic nerve, spinal cord, sciatic nerve, draw materials in same area, fixed with 10% formalin.It incite somebody to action this Invention medicine high dose group and blank control group Rats Organs and Tissues sample carry out histotomy, carry out pathological examination, remaining sample Retain with standby.As a result：Through to two groups of animal viscera tissue specimen inspections, each organ-tissue structure is normal, and cell dyeing is equal It is even, change without obvious.Pathological change is caused because the organ-tissue that medicine high dose group animal of the present invention is examined does not occur medicine, Therefore organ-tissue section is not carried out to medicine middle dose group of the present invention and low dose group.Tested organ-tissue form section photo and Pathological section report is attached.

Pathological observation result shows that the histocyte of each all multi visceras of administration group rat is harmless, and prompting should on morphology Medicine is free of toxic effects to each organs and tissues.

5th, conclusion

Rat chronic toxicity test result shows, with medicine 4.620g/kg, 2.310g/kg, 1.155g/kg body of the present invention Weight is twice a day, continuous 13 weeks big equivalent to 60 times, 30 times, 15 times intended with clinical children's daily dose 0.077g/kg body weight Mouse gastric infusion and be discontinued 2 weeks, compared with blank control group；General state (mode of appearance, work to rat is administered in each dosage Dynamic, stool shape etc.), grow (body weight increase), hematopoiesis function (hematological examination), Liver and kidney function (blood biochemical analysis), Vitals ponderal index, find no obvious toxic action；Proved through pathological examination, children's return of spring ball high dose group With blank control group comparative observation, to the rat heart, liver, spleen, lung, kidney, adrenal gland, thymus gland, brain, hypophysis, uterus, ovary, testis Ball, epididymis, prostate, thyroid gland, tracheae, oesophagus, stomach, sustainer, duodenum, ileum, colon, bladder, pancreas, lymph The histoorgans such as knot, optic nerve, spinal cord, sciatic nerve do not find obvious toxic damages change.Because medicine of the present invention is high Each histoorgan of dosage group animal does not occur obvious pathological change, therefore medicine middle dose group of the present invention, low dose group are not carried out Organ-tissue section detection, its Saving specimen are standby.

In summary, the high, medium and low Three doses of medicine of the present invention (4.620,2.310,1.155g/kg) are long-term (13 weeks) Administration and withdrawal observation 2 weeks, to rat behavior activity, grow (body weight increase), food ration (feed consumption), blood cell , blood biochemical analysis, organ index, organ-tissue morphology etc. are without notable toxic effect.Prompt Clinical practice safety.

The acute toxicity test of experimental example 3

1 experiment material

1.1 medicine

Medicine (being prepared by embodiment 1) of the present invention.

With 1-3 year, day dose 1.08g is counted for this research, and body weight is calculated by 3 × 2+8=14kg, i.e., clinical consumption per day is 0.077g/kg.The suspension oral gavage for facing used time concentration needed for distilled water is configured to is administered.

1.2 animal

Kunming mouse, male and female half and half, body weight 12-14g, by Military Medical Univ No.3, P.L.A experimental animal The heart provides, credit number：SCXK- (army) 2012-0003.

1.3 feed

Feed is full-valence pellet feed, is provided by above-mentioned unit.

1.4 zoopery places

Guiyang College of Traditional Chinese Medicine's pharmacological toxicology laboratory ventilation is good, sanitation and hygiene, 20-25 DEG C of temperature, humidity 55%- 65%.The other sub-cage rearing of animal unisexuality, free water feed.

1.5 key instrument

ALC-210.3 type electronic balances, upper current chart level instruments and meters Co., Ltd.

1.6 statistical procedures

Data use the poor opposite sex between group, withRepresent, carry out t inspections.

2 experimental methods and result

2.1 preruns are tested

With the pharmaceutical aqueous solution of the present invention of Cmax 20%, gavage of 0.4ml/10g body weight gives mouse, observation 3 My god.As a result：Animal dead is had no, shows that its LD can not be determined₅₀, therefore determine the maximum dosage-feeding of medicine of the present invention.

2.2 formal test

Kunming mouse 40 is taken, is randomly divided into blank control group, medicine group of the present invention, every group 20, male and female half and half.It is real Water 12h is can't help in fasting before testing, and medicine group gavage of the present invention gives the pharmaceutical aqueous solution 0.4ml/10g bodies of the present invention of mouse 20% Weight, two times a day, equivalent to 16g/kg body weight, for 208 times of clinical plan dosage 0.077g/kg body weight；Blank control group with Same amount of physiological saline gavage, two times a day.Continuous Observation 14d after administration, record animal have non-toxic reaction and experiment Front and rear changes of weight, not produce the dosage of death as maximum dosage-feeding.

Experimental result is shown in Table 26.

Table 26 to mouse weight (g) influence (N=10)

Note：Children's return of spring ball group female P compared with blank control group female>0.05；Children's return of spring ball group male and blank Control group male relatively P>0.05.

As a result：After Kunming mouse gavage pharmaceutical aqueous solution 16g/kg of the present invention, development is healthy, fleshiness, and hair is close And glossy, the secretion that eyes are bright and flexible, without exception, crissum are clean, ingest normal, four limbs are healthy and strong, and spontaneous activity is just Often, body weight gradually increases in the observation period, the no significant difference compared with blank control group.Have no that animal dead and poison are secondary anti-in 14d Should.Visually become celestial at the end of experiment and have no obvious pathological change.

3 conclusions

Mouse orally gives 16g/kg body weight medicine of the present invention in one day after, Continuous Observation 14 days, animal survives, mouse Outward appearance, behavior, breathing state, position and posture, the reaction of stimulation, substantially cut open inspection are showed no obvious abnormalities.Before medicine, after medicine 7 days and 14 days medicine groups of the present invention are female, male mice body weight is not significantly different with same sex blank control group mouse.

In this medicine Mouse oral acute toxicity test of the present invention, mouse gives maximum dosage-feeding 16g/kg body weight, Equivalent to 208 times of clinical application amount, have no that overt toxicity reacts.

Compared with prior art, medicine is made using above-mentioned raw materials in the present invention, and each component raw material has collaboration work(well Can, manufactured medicine has the effect of clearing heat and detoxicating, saturating table slit phlegm.For acute infantile convulsion, typhoid fever heating, face night fever, urine Band blood, dimly visible do not go out of measles and cause body heat cough；Dysentery characterized by blood in the stool, watery diarrhea, dyspepsia, stomachache.It is evident in efficacy, Small side effects, reach The purpose of invention.

Invention is further described with reference to embodiment, but is not intended as the foundation limited the present invention.

Embodiment：

Embodiment 1.

Formula:Coptis 25g, PULVIS CORNUS BUBALI CONCEN TRATUS 50g, cornu caprae hircus 25g, calamitas urinae hominis (forge) 25g, Fermented Soybean 25g, folium isatidis 50g, schizonepeta 50g, notopterygium root 50g, root of kudzu vine 50g, glutinous rehmannia 50g, caulis clematidis armandii 50g, radix paeoniae rubrathe 50g, radix scutellariae 50g, root of purple-flowered peucedanum 75g, radix scrophulariae 75g, balloonflower root 75g, radix bupleuri 37.5g, Chinese tamarisk tops 37.5g, rattletop 20g and great burdock achene (stir-fry) 75g.

Technique:Take cornu caprae hircus to be ground into fine powder to mix with PULVIS CORNUS BUBALI CONCEN TRATUS, it is standby；Remaining medicinal material respectively takes 2/3 amount to crush It is standby into fine powder, sieving, fine powder；Coarse powder carries cream with remaining medicinal material boiling, and cream mixes general ball with above-mentioned powder, dries, coating, i.e., .

Usage and dosage:Orally, one-year-old following baby clothes 1, take 2 for 1~2 years old, take within 3~4 years old 3, take within 5~7 years old 5, 2~3 times on the one.

Specification：Often pipe fills 5, weight 0.9g.

Embodiment 2.

Formula：Coptis 85g, PULVIS CORNUS BUBALI CONCEN TRATUS 120g, cornu caprae hircus 85g, calamitas urinae hominis (forge) 85g, Fermented Soybean 85g, smalt Leaf 120g, schizonepeta 120g, notopterygium root 120g, root of kudzu vine 120g, glutinous rehmannia 120g, caulis clematidis armandii 120g, radix paeoniae rubrathe 120g, radix scutellariae 120g, the root of purple-flowered peucedanum 150g, radix scrophulariae 150g, balloonflower root 150g, radix bupleuri 90g, Chinese tamarisk tops 90g, rattletop 60g and great burdock achene (stir-fry) 150g.

Technique:Take cornu caprae hircus to be ground into fine powder to mix with PULVIS CORNUS BUBALI CONCEN TRATUS, obtain mixed powder, it is standby；Remaining medicinal material boiling Cream, cream and above-mentioned mixed powder and the cane sugar powder and 20% dextrin mixing granulation of medicinal extract amount 20% are carried, dries, produces.

Specification：Every 0.5g.

Usage and dosage:2 times a day, 3 tablets each time, orally.

Embodiment 3.

Formula：Coptis 5g, PULVIS CORNUS BUBALI CONCEN TRATUS 10g, cornu caprae hircus 5g, calamitas urinae hominis (forge) 5g, Fermented Soybean 5g, folium isatidis 10g, schizonepeta 10g, notopterygium root 10g, root of kudzu vine 10g, glutinous rehmannia 10g, caulis clematidis armandii 10g, radix paeoniae rubrathe 10g, radix scutellariae 10g, root of purple-flowered peucedanum 20g, radix scrophulariae 20g, balloonflower root 20g, radix bupleuri 5g, Chinese tamarisk tops 5g, rattletop 5g and great burdock achene (stir-fry) 20g.

Technique：Take cornu caprae hircus to be ground into fine powder to mix with PULVIS CORNUS BUBALI CONCEN TRATUS, obtain mixed powder, it is standby；Remaining medicinal material boiling Cream is carried, cream is mixed with above-mentioned mixed powder and the starch of medicinal extract amount 20%, tabletting, film coating, produced.

Specification：Every 0.5g.

Usage and dosage:2 times a day, each 10-20g, orally.

Claims

A kind of 1. oral formulations for treating fever in children infantile convulsion, it is characterised in that：Calculate in parts by weight, by 25 parts of the coptis, water Ox horn concentration 50 parts of powder, 25 parts of cornu caprae hircus, forge 25 parts of calamitas urinae hominis, 25 parts of Fermented Soybean, 50 parts of folium isatidis, 50 parts of schizonepeta, notopterygium root 50 Part, 50 parts of the root of kudzu vine, 50 parts of glutinous rehmannia, 50 parts of caulis clematidis armandii, 50 parts of the radix paeoniae rubrathe, 50 parts of radix scutellariae, 75 parts of the root of purple-flowered peucedanum, 75 parts of radix scrophulariae, 75 parts of balloonflower root, 37.5 parts of radix bupleuri, 37.5 parts of Chinese tamarisk tops, 20 parts of rattletop, 75 parts of stir-baked FRUCTUS ARCTII are prepared.
2. the preparation method of the oral formulations for the treatment of fever in children infantile convulsion as claimed in claim 1, it is characterised in that：Take above-mentioned medicine Thing, conventionally extracted, auxiliary material is combined or be not added with conventional pharmaceutical adjuvants, traditional drug formulations are made.
3. the preparation method of the oral formulations for the treatment of fever in children infantile convulsion as claimed in claim 2, it is characterised in that：It is described oral Preparation is pill, granule, tablet or capsule.
4. the preparation method of the oral formulations for the treatment of fever in children infantile convulsion as claimed in claim 3, it is characterised in that：The pill It is prepared：Take cornu caprae hircus to be ground into fine powder to mix with PULVIS CORNUS BUBALI CONCEN TRATUS, it is standby；Remaining medicinal material respectively takes 2/3 amount to be ground into carefully Powder, sieving, fine powder are standby；Coarse powder carries cream with remaining medicinal material boiling, and cream mixes general ball with above-mentioned powder, dries, and coating, produces.
5. the preparation method of the oral formulations for the treatment of fever in children infantile convulsion as claimed in claim 3, it is characterised in that：The particle Agent is prepared：Take cornu caprae hircus to be ground into fine powder to mix with PULVIS CORNUS BUBALI CONCEN TRATUS, obtain mixed powder, it is standby；Remaining medicinal material boiling carries Cream, cream and above-mentioned mixed powder and the cane sugar powder and 20% dextrin mixing granulation of medicinal extract amount 20%, dry, produce.
6. the preparation method of the oral formulations for the treatment of fever in children infantile convulsion as claimed in claim 3, it is characterised in that：The tablet It is prepared：Take cornu caprae hircus to be ground into fine powder to mix with PULVIS CORNUS BUBALI CONCEN TRATUS, obtain mixed powder, it is standby；Remaining medicinal material boiling carries cream, Cream mixes with above-mentioned mixed powder and the starch of medicinal extract amount 20%, tabletting, film coating, produces.
7. the preparation method of the oral formulations for the treatment of fever in children infantile convulsion as claimed in claim 3, it is characterised in that：The capsule Agent is prepared：Take cornu caprae hircus to be ground into fine powder to mix with PULVIS CORNUS BUBALI CONCEN TRATUS, obtain mixed powder, it is standby；Remaining medicinal material is with 70% Alcohol reflux extracts, and extract solution recovery ethanol is simultaneously condensed into medicinal extract, the starch of medicinal extract and above-mentioned mixed powder and medicinal extract amount 20% and 0.6% magnesium stearate mixes, and with 60% alcohol granulation, dries, filling, produces.