CN1813780A

CN1813780A - Chinese medicine composition for treating cold fever and liver damage and its preparing method

Info

Publication number: CN1813780A
Application number: CN 200510101825
Authority: CN
Inventors: 苏子仁; 赖小平; 陈建南
Original assignee: Guangzhou University of Chinese Medicine
Current assignee: Guangzhou University of Chinese Medicine
Priority date: 2005-12-01
Filing date: 2005-12-01
Publication date: 2006-08-09
Anticipated expiration: 2025-12-01
Also published as: CN100431548C

Abstract

The present invention discloses a Chinese medicine composition for curing high fever due to exopathy and acute and chronic hepatic injury. It is formed from the following components: (by weight portion) 1-50 portions of taurine, 1-50 portions of baicalin and 1-50 portions of puerarin.

Description

A kind of Chinese medicine ingredients compositions and preparation method that is used for the treatment of exogenous high fever and acute and chronic liver injury

Technical field

The present invention relates to a kind of Chinese medicine active ingredient composition, can be used for diseases such as exogenous high fever and acute and chronic liver injury.

Background technology

At present, it is numerous to be used for the Chinese patent medicine of Chinese prescription of diseases such as exogenous high fever and hepatic injury on the market.The preparation of making by cow-bezoar bolus for resurrection side (as 'An Gong Niu Huang Wan ' sheet, capsule, powder, suppository etc.) and on the basis of cow-bezoar bolus for resurrection the preparation (as new cow-bezoar bolus for resurrection, new 'An Gong Niu Huang Wan ' pin, QINKAILING ZHUSHEYE, oral liquid, nasal drop etc.) of the plus-minus side of spreading out be used for the treatment of exogenous high fever and acute and chronic liver injury effective; GEGEN QINLIAN TANG also is effective prescription of treatment exogenous high fever, and its effective Chinese medicine that falls heat is Radix Puerariae, Radix Scutellariae; Taurine and Radix Puerariae compatibility can be used for exogenous high fever and acute and chronic liver injury.But Chinese medicine ingredients is not clear, and quality can not be controlled fully, and the mechanism of action is unclear, has not only influenced drug effect, and makes injection and easily have side effects.As using more QINKAILING ZHUSHEYE clinically, its main component is pig, cattle, sheep cholic acid, Cornu Bubali, Radix Scutellariae, Concha Margaritifera, Fructus Gardeniae, Radix Isatidis, Moschus, Borneolum Syntheticum, Herba Menthae 9 flavor Chinese medicines (comprising 2 kinds of Chinese medicine monomer compositions) compositions, because preparation technology is tediously long, unstable product quality, product qualified rate is low.The untoward reaction type of QINKAILING ZHUSHEYE is more, and the reason that the untoward reaction of statistical literature report QINKAILING ZHUSHEYE is analyzed has:

1) the medical material ingredient has protein, chlorogenic acid, Saponin etc., can be used as antigenic substance and enters some responsive antibody of body internal stimulus and cause allergy, and wherein Calculus Bovis, Cornu Bubali may contain foreign protein.After foreign protein enters in the body, can stimulate body to produce corresponding antibodies, and cause untoward reaction;

2) not divisible and cause allergy as compound preparation impurity in separation process;

3) cosolvent in the preparation can be used as antigen and sensitization;

4) relevant with idiosyncrasy.

Along with clinical practice is increasing, the QINGKAILING untoward reaction also increases thereupon.Mainly concentrate on allergy, show as erythra, pimple, pruritus, urticaria sample drug eruption, can die away after the general drug withdrawal, serious adverse reaction is an anaphylactic shock.

Summary of the invention

The object of the present invention is to provide clear and definite, quality controllable, the safe in utilization Chinese medicine ingredients composition and method of making the same that effectively is used for the treatment of exogenous high fever and acute and chronic liver injury of a kind of effective ingredient.

Technical solution of the present invention is: it is made up of following traditional Chinese medicine components by weight: taurine 1～50 weight portion, baicalin 1～50 weight portion, puerarin 1～50 weight portion.

As preferred scheme, it is made up of following traditional Chinese medicine components by weight: taurine 10～40 weight portions, baicalin 5～30 weight portions, puerarin 2～20 weight portions.

As most preferred scheme, it is by taurine 25 weight portions, baicalin 10 weight portions, and puerarin 5 weight portions are formed.

Effective ingredient taurine with Calculus Bovis in the side is monarch.The Calculus Bovis bitter in the mouth is cool in nature, and gas perfume (or spice) kind clears away heart-fire, hepatomegaly heat, the function heat-clearing and toxic substances removing, eliminate the phlegm have one's ideas straightened out, the endogenous wind stopping relieving convulsion.Shennong's Herbal is called its " main infantile convulsion cold and heat, intenseness of heat Kuang Chi ".It is used for exogenous high fever, faints from fear and twitch with having two: one with cool liver endogenous wind stopping relieving convulsion; One with the refreshment of having one's ideas straightened out of eliminating the phlegm, and is used for expectorant and covers clear key, unconsciousness and delirium.So be the key medicine of controlling diseases such as hyperpyrexia that epidemic febrile disease heat falls into intenseness of heat heated due to the pericardium, extreme heat causing wind syndrome, agitation, coma, delirium, spasm tic.Being equipped with Radix Scutellariae is minister, its property bitter cold, and the main lung meridian of returning, bitter energy dampness, the heat clearing away of cold energy, thus the effect of heat clearing and damp drying is arranged, and " book on Chinese herbal medicine just ": " fire of the clear part of the body cavity above the diaphragm housing the heart and lungs of Radix Scutellariae, expectorant promoting the circulation of QI." and can clearing away heat-fire detoxifcation, damp-heat in upper-JIAO among the You Shanqing both can help the pyretic toxicity of the clear removing pathogen in the heart bag of Calculus Bovis; The expectorant that closes strongly fragrant pericardium of can dispelling again is turbid, with Calculus Bovis with the Li Gengsheng of heat-clearing and toxic substances removing then, the merit benefit work of waking up the patient from unconsciousness by dissipating phlegm.Radix Puerariae suffering, sweet, cool is gone into spleen, stomach warp, the function expelling pathogenic factors from muscles for reducing heat, and promoting the production of body fluid to quench thirst, " book on Chinese herbal medicine dredge through ": " Radix Puerariae, the key medicine of dismissing positive bright epidemic febrile disease pathogenic heat also, thus main quenching one's thirst, high fever of the body, heat heap soil or fertilizer over and around the roots chest and diaphragm is vomitted." be to be adjuvant drug, it is with having three: one, the power of getting its dispelling exopathogens from superficies of the body, with the heresy invasion and attack flesh table of controlling the diseases caused by exogenous pathogenic factor six climate exopathogens, epidemic febrile disease from the beginning of exogenous high fever; Its two, the merit of getting its expelling pathogenic factors from muscles for reducing heat is used for the muscle twitches person that infantile hyperpyrexia causes, more than is all assistant and helps and use it; Its three, this product still can promoting the production of body fluid to quench thirst, with the property of the too bitter dry impairment of YIN of system a kind of reed mentioned in ancient books cattle, uses it for the assistant system again; Take a broad view of full side, with the product of the removing heat in the liver for detoxication that clears away heart-fire with eliminate phlegm for resuscitation that to ward off turbid product compatible, be intended to let out clearly and close strongly fragrant expectorant heat; And help with expelling pathogenic factors from muscles for reducing heat, the product of dispelling exopathogens from superficies of the body are to help the removing summer-heat hyperpyrexia, and the monarch and his subjects are orderly, and compatibility is rigorous, and all medicines share, and play waking up the patient from unconsciousness by clearing away heat altogether, the eliminating phlegm detoxifcation, the merit of expelling pathogenic factors from muscles for reducing heat makes pyretic toxicity clear, turbidization of expectorant, the key make and break, the mind is peaceful, and all diseases are all removed.We are made up of Calculus Bovis, Radix Scutellariae, Radix Puerariae three the effective elements of the medicine taurines, baicalin, puerarin, and are identical with the Chinese medical theory of medical material prescription.

Preparation technology's method of the present invention is: above three flavors, mix, and add right amount of auxiliary materials, mixing is made acceptable clinically various dosage forms.

Aforementioned pharmaceutical compositions can add adjuvant or excipient is made clinical acceptable forms, as preparations such as drug administration by injection, oral administration such as injection, powder pin, transfusion, mixture, tablet, capsule, soft capsule, pill, drop pill, granules.

Wherein the preparation method of medicaments injection of the present invention is: get above three flavors, be dissolved in water, adjust pH value to 6.0-8.0 with sodium hydroxide solution, filter, filtrate is potted in the ampoule, and sterilization obtains injection;

The preparation method of the powder pin of medicine of the present invention is: get above three flavors, be dissolved in water, adjust pH value to 6.0-8.0 with sodium hydroxide solution, filter, be potted in the powdery ampoule after the filtrate sterilization, sterilization obtains the powder pin once more;

The preparation method of the mixture of medicine of the present invention is: get above three flavors, be dissolved in water, adjust pH value to 6.0-8.0 with sodium hydroxide solution, filter, add correctives, be potted in the oral liquid bottle, obtain mixture;

The preparation method of the tablet of medicine of the present invention is: get above three flavors, add starch, carboxymethyl cellulose, granulate, tabletting obtains tablet;

The preparation method of the capsule of medicine of the present invention is: get above three flavors, add starch, carboxymethyl cellulose, granulate, capsule is good in fill, obtains capsule;

The preparation method of the soft capsule of medicine of the present invention is: get above three flavors, add vegetable oil, granulate, the fill capsule obtains soft capsule;

The preparation method of the pill of medicine of the present invention is: get above three flavors, add starch, refined honey, general ball obtains pill;

The preparation method of the drop pill of medicine of the present invention is: get above three flavors, add Polyethylene Glycol, obtain drop pill;

The preparation method of the granule of medicine of the present invention is: get above three flavors, add starch, carboxymethyl cellulose, granulate, obtain granule.

The middle pharmaceutically active ingredient compound recipe that pharmaceutical composition of the present invention is made up of three kinds of monomer effective ingredient, anaphylactogens such as no protein, chlorogenic acid, Saponin exist, prescription is clear and definite, the controllable degree height, place to go unknown impuritie to greatest extent in the preparation process, the controlled material that makes Chinese medicine ingredients compositions of the present invention is more than 95%; The present invention is made up of Calculus Bovis, Radix Scutellariae, Radix Puerariae three the effective elements of the medicine taurines, baicalin, puerarin, taurine, baicalin, puerarin all have legal injection drug standard to record, the effect of heat-clearing and toxic substances removing, expelling pathogenic factors from muscles for reducing heat is all arranged, be again the good material of water solublity simultaneously, technology is simple and easy to control, is easy to make injection; Medicament composing prescription meets Chinese medical theory, and three medicine mutual-assistance compatibilities have synergistic function preferably to treatment exogenous high fever and acute and chronic liver injury.

Advantage of the present invention is: clear, the quality controllable degree height of effective ingredient, pharmacological action mechanism are clear and definite, safe.

Pharmaceutical composition of the present invention has following pharmacological action: can significantly suppress the rising of rat fever body temperature due to the yeast; Xylol induced mice auricle edema acute inflammation model has obvious inhibitory action; Thermostimulation induced mice pain all there is significant analgesia role; Isolated ileum segments in guinea pigs anaphylaxis is shunk the inhibitory action that highly significant is arranged; Energy significant prolongation mice swimming time; Can significantly strengthen the cytophagous phagocytic function of mouse monokaryon.Canavaline (Con A) induced mice immunologic liver injury there is good protective action, CCl4 and ethanol induced mice acute liver damage are had good protective action.The above pharmacological action of this pharmaceutical composition is used for exogenous high fever for it is clinical and acute and chronic liver injury provides experimental basis.

Test furthermore bright effect of the present invention below in conjunction with some:

The pharmacodynamics test of experiment one, treatment exogenous high fever and acute and chronic liver injury

1, rat fever experiment due to the yeast

Summary: to rat injection pyrogen (yeast), animal body is produced and the release endogenous pyrogen, cause fervescence, give the rat normal saline then respectively, the injection of the present invention of three kinds of various dose, QINKAILING ZHUSHEYE, with after the thermometer measure administration 2,3,4,5,6, the situation of change of 7h rat temperature, the record result, with different time take temperature and basal body temperature difference is the index that body temperature changes, it is abscissa that the result was inserted with time, temperature difference is in the figure of vertical coordinate, judges the refrigeration function of each medicine with the situation of change of fervescence curve.

1.1 experiment purpose: study injection antipyretic effect of the present invention

1.2 experiment material:

Be subjected to reagent: injection of the present invention, Traditional Chinese Medicine University Of Guangzhou new drug development research center provides

Positive control drug: QINKAILING ZHUSHEYE: Pharmaceutical Factory of Beijing University of Chinese Medicine provides, authentication code: the accurate word Z11020269 of traditional Chinese medicines, batch number: 511208A.

The side's of tearing open contrast medicine: puerarin injection, baicalin for injection liquid, taurine injection provide by Traditional Chinese Medicine University Of Guangzhou new drug center.

Material and reagent: the sharp board dry yeast of horse is made into 20% solution with sodium chloride injection.Omron MC-107BW electronic clinical thermometer.

Laboratory animal: the SD rat, Traditional Chinese Medicine University Of Guangzhou's animal center provides.The SPF level is normally raised after 3 days for examination.

1.3 experimental technique and result:

With 160～200g rat; female unpregnancy; 100, be divided into eight groups at random: blank group, QINKAILING ZHUSHEYE positive controls; the basic, normal, high dosage group of injection of the present invention (is equivalent to 5,10,20 times of clinical dosage according to the weight; the dosage of middle dosage group is identical with QINKAILING ZHUSHEYE), puerarin injection group, baicalin for injection liquid group; the taurine injection group, 12 every group.The normal raising begins experiment after three days.Measure rat temperature once morning and afternoon every day, and continuous measurement 2 days discards the rat that body temperature changes excessive (〉=1 ℃).During experiment; every treated animal abdominal cavity subcutaneous injection 20% dry yeast solution 10ml/kg; difference intramuscular injection normal saline, injection of the present invention, QINKAILING ZHUSHEYE, puerarin injection group, baicalin for injection liquid group, taurine injection after 3 hours, dosage sees Table 1.With after the thermometer measure administration 2,3,4,5,6, the situation of change of 7h rat temperature, the record result, with different time take temperature and basal body temperature difference is the index that body temperature changes, it is abscissa that the result was inserted with time, temperature difference is in the figure of vertical coordinate, judges the refrigeration function of each medicine with the situation of change of fervescence curve.Result such as following table 1.

The influence that table 1 injection of the present invention raises to yeast pyrogenicity rat temperature (x ± s)

Group	N	Dosage (ml/kg)	The 2h fervescence (℃)	The 3h fervescence (℃)	The 4h fervescence (℃)	The 5h fervescence (℃)	The 6h fervescence (℃)	The 7h fervescence (℃)
Group	N	Dosage (ml/kg)	The 2h fervescence (℃)	The 3h fervescence (℃)	The 4h fervescence (℃)	The 5h fervescence (℃)	The 6h fervescence (℃)	The 7h fervescence (℃)	Blank qingkailing injections parenteral solution of the present invention parenteral solution of the present invention parenteral solution puerarin injection of the present invention baicalin for injection liquid taurine injection	11 10 10 10 10 10 10 10	- 1.33 1.33 0.67 0.33 1.33 1.33 1.33	1.23±0.30 1.24±0.50 0.96±0.42 1.41±0.45 1.38±0.42 1.26±0.22 1.9±0.51 #$ 1.82±0.38 #$	1.95±0.32 1.66±0.25 * 1.63±0.31 * 1.6±0.36 * 1.95±0.38 1.51±0.38 * 1.71±0.53 2.06±0.42 #	2.14±0.39 1.87±0.38 1.70±0.43 * 1.81±0.53 1.99±0.45 1.62±0.44 * 1.61±0.47 * 1.85±0.36	2.08±0.35 1.79±0.51 2.02±0.43 1.82±0.36 2.03±0.46 1.83±0.45 2.14±0.55 2.21±0.38$	1.92±0.51 1.73±0.52 1.96±0.34 2.04±0.47 2.15±0.60 1.84±0.38 2.03±0.78 2.35±0.37 ##	1.64±0.38 1.64±0.46 1.72±0.35 1.79±0.34 1.87±0.39 2.03±0.28 # 2.16±0.60 # 2.06±0.43 #

Annotate: compare * P＜0.05, * * P＜0.01 with the blank group; Compare #P＜0.05, ##P＜0.01 with the QINKAILING ZHUSHEYE group; Compare $P＜0.05 ， $$P＜0.01 with dosage in the injection of the present invention.

Table 1 result shows, compare with the blank group, each dosage group of injection of the present invention, the puerarin injection group, baicalin for injection liquid group all can suppress yeast pyrogenicity rat temperature to a certain extent and raise, and injection high dose group of the present invention raises to yeast pyrogenicity rat temperature has inhibitory action (P＜0.05) at 3h, 4h; The dosage group has inhibitory action (P＜0.05) at 3h in the injection of the present invention; Injection low dose group of the present invention is at each time point inhibitory action no difference of science of statistics (P＞0.05); The QINKAILING ZHUSHEYE group has inhibitory action (P＜0.05) at 3h; The puerarin injection group raises to yeast pyrogenicity rat temperature has inhibitory action (P＜0.05) at 3h, 4h; Baicalin for injection liquid group raises to yeast pyrogenicity rat temperature has inhibitory action (P＜0.05) at 4h; Taurine injection does not all have obvious inhibitory action (P＞0.05) at each time point.Compare with the QINKAILING ZHUSHEYE group, the basic, normal, high dosage group of injection of the present invention is the equal no difference of science of statistics of each time point (the P value all＞0.05).The side of tearing open studies show that, the puerarin injection group, and baicalin for injection liquid group has all shown certain refrigeration function, but the taurine injection group does not have refrigeration function; Compare with dosage group in the injection of the present invention; the puerarin injection group is in each time point zero difference (P＞0.05); there were significant differences at 2h for baicalin for injection liquid group (the P value all＜0.05); there were significant differences at 2h, 3h, 5h for the taurine injection group (the P value all＜0.05); injection effect of the present invention is better than the side's of tearing open baicalin, puerarin, taurine administration group, and pointing out three medicine compatibilities to use has certain synergistic function.

1.4 discuss

1. from the amplitude analysis of pyrogenicity rat unit time fervescence, injection high dose group rising amplitude of the present invention is substantially less than middle dosage group, and middle dosage group is substantially less than low dose group, and the refrigeration function of visible injection of the present invention is a certain amount of effect relationship trend.2. from the side's of tearing open compatibility angle analysis; baicalin for injection liquid, puerarin injection have certain refrigeration function; taurine injection is not seen the trivial solution heat effect, and three's compatibility can prolong the refrigeration function to the pyrogenicity rat, demonstrates to have certain compatibility potentiation.3. dosage group dosage is consistent with the QINKAILING ZHUSHEYE group in the injection injection of the present invention, and both refrigeration function results do not have significant difference, prompting injection of the present invention to separate thermal effect similar to QINGKAILING.

2, dimethylbenzene induced mice auricle edema experiment

Summary: it is wide mucocutaneous to utilize dimethylbenzene to stimulate mice one to pick up the ears, make its auricle edema, ear weight increases after the edema, cuts ears this moment and weighs and calculate two ear weight differentials, the ear thickness that compares blank group, administration group mice, thereby the antiphlogistic effects of judgement injection.

2.1 experiment purpose: study the antiphlogistic effect of injection of the present invention

2.2 experiment material:

Positive control drug: prednisolone acetate, the 5mg/ sheet, Guangdong Huanan Pharmaceutical Co., Ltd produces, lot number: 050301; QINKAILING ZHUSHEYE: Pharmaceutical Factory of Beijing University of Chinese Medicine provides, batch number: 511208A.

Material and reagent: dimethylbenzene: chemical pure, Guangzhou Chemical Reagent Factory production, lot number: 0203428; BS110S electronic balance: Sartorius company product.

Laboratory animal: the NIH mice, Traditional Chinese Medicine University Of Guangzhou's animal center provides.The SPF level is normally raised after 3 days for examination.

2.3 experimental technique and result:

Only get NIH mice 22～25g90; male and female half and half; be divided into 9 groups at random: blank group; the prednisolone acetate positive controls; the QINKAILING ZHUSHEYE positive controls; the basic, normal, high dosage of injection of the present invention (is calculated 10,20,40 times that are equivalent to clinical dosage by weight; the dosage of middle dosage group baicalin is identical with QINKAILING ZHUSHEYE) group; the puerarin injection group; baicalin for injection liquid group; the taurine injection group is except that the prednisolone acetate gastric infusion, and all the other each groups all adopt administered intramuscular.Dosage sees Table 1.30min after the administration, every group of mice one auricle melted paraxylene 0.03ml; Each treated animal again by above-mentioned dosed administration once behind the 15min, 45min puts to death each Mus, the mice ears is downcut the precision two ear weight of weighing with diameter 0.6cm card punch with the position homalographic, obtain weight difference, the t check relatively ear weight differential of each treated animal has or not significance.The results are shown in Table 2.

The influence of table 2 injection xylol of the present invention induced mice auricle edema (x ± s)

Group	Animal number of elements (only)	Dosage (ml/kg)	Ear swelling degree (mg)
Group	Animal number of elements (only)	Dosage (ml/kg)	Ear swelling degree (mg)	Blank prednisone acetate qingkailing injections parenteral solution of the present invention parenteral solution of the present invention parenteral solution baicalin for injection of the present invention liquid puerarin injection taurine injection	10 10 10 10 10 10 10 10 10	- 4.0mg 1.33 0.67 1.33 2.66 1.33 1.33 1.33	19.28±5.84 8.97±3.23 10.75±6.23 10.88±4.72 10.19±2.27 9.62±5.69 11.53±4.35 12.06±5.31** 12.67±6.87*

Annotate: compare * p＜0.05, * * p＜0.01 with the blank group; Compare with QINKAILING ZHUSHEYE: #p＜0.05, ##p＜0.01; Compare: $p＜0.05 ， $$p＜0.01 with prednisolone acetate; Compare ， ﹠amp with dosage in the injection of the present invention; P＜0.05﹠amp; ﹠amp; P＜0.01

Table 2 result shows; Compare with the blank group, the basic, normal, high dosage of injection of the present invention can significantly alleviate the ear swelling degree (P＜0.01) of the scorching mice of caused by dimethylbenzene xylene, and Chinese medicine positive drug QINKAILING ZHUSHEYE, Western medicine positive drug prednisolone acetate also can significantly alleviate the ear swelling degree (P＜0.01) of mice.Swelling degree and blank group more variant (P＜0.01 or P＜0.05) behind baicalin, puerarin, each administration group Mice Auricle melted paraxylene of taurine compare no difference of science of statistics with two kinds of positive control drugs, show that the anti-acute inflammation effect of each medicine is remarkable.In the side's of tearing open baicalin, puerarin, each administration group of taurine, with the best as a result of baicalin for injection liquid, puerarin injection takes second place, after taurine injection is; Though with dosage result no difference of science of statistics (P＞0.10) in the injection of the present invention, injection effect of the present invention is better than the side's of tearing open baicalin, puerarin, taurine administration group, shows that three kinds of compositions share certain synergistic function.

2.4 discuss

1. the antiinflammatory action of injection of the present invention is not seen and is dose-effect relationship, and possible dosage is excessive relevant.2. from the side's of tearing open compatibility angle analysis, the antiinflammatory action of baicalin is the strongest, and puerarin takes second place, after taurine is; Three's dosage is identical with dosage in the injection of the present invention, therefore can infer that each composition of injection of the present invention has certain synergistic function on antiinflammatory action.3. from the result of the anti-mice caused by dimethylbenzene xylene ear swelling of above injection of the present invention effect, it has obvious mitigation to the chmice acute inflammation; The QINKAILING ZHUSHEYE dosage is identical with dosage in the injection of the present invention, and both effects are close, and the effect of injection low dosage of the present invention then is better than QINKAILING ZHUSHEYE, and the little and effect of dosage significantly.

3, the sedation of injection of the present invention

Summary: the research medicine is to the influence of spontaneous activity in mice, give mice normal saline, the injection of the present invention of three kinds of various dose, QINKAILING ZHUSHEYE, pentobarbital sodium respectively, use the movable number of times of mice autonomic activities analyzer observed and recorded mice, the autonomic activities number of times that compares blank group, administration group mice, thereby the sedation effect of judgement injection.

3.1 experiment purpose: study injection abirritative effect of the present invention

3.2 experiment material:

Positive control drug: Ethylurethanm (urethanes), analytical pure, Chemical Reagent Co., Ltd., Sinopharm Group produces; QINKAILING ZHUSHEYE: Pharmaceutical Factory of Beijing University of Chinese Medicine provides, authentication code: the accurate word Z11020269 of traditional Chinese medicines, batch number: 511208A.

Material and reagent: XZC-4 type toy autonomic activities analyzer.

3.3 experimental technique and result:

Get NIH mice 22～25g; 118; male and female half and half are divided into 9 groups at random: blank group, Ethylurethanm positive controls; the QINKAILING ZHUSHEYE positive controls; the basic, normal, high dosage group of injection of the present invention (be equivalent to 10,20,40 times of clinical dosage according to the weight, the dosage of middle dosage group is identical with QINKAILING ZHUSHEYE), the puerarin injection group; baicalin for injection liquid group, the taurine injection group.Each group all adopts administered intramuscular.Dosage sees Table 1.Respectively at behind 30min, the 60min after the administration mice being placed in the XZC-4 type toy autonomic activities analyzer the movable number of times of mice in the record 5min.Make mice adapt to behind the 5min the movable number of times of record again before each the mensuration earlier.The movable number of times that compares each treated animal with the t check has or not significance.The results are shown in Table 3.

Table 3 injection of the present invention is to the influence of spontaneous activity in mice (x ± s)

Group	The animal number of elements	Dosage (ml/kg)	30min mice autonomic activities number of times	60min mice autonomic activities number of times
Group	The animal number of elements	Dosage (ml/kg)	30min mice autonomic activities number of times	60min mice autonomic activities number of times	Blank Ethylurethanm qingkailing injections parenteral solution of the present invention parenteral solution of the present invention parenteral solution baicalin for injection of the present invention liquid puerarin injection taurine injection	12 12 12 12 12 12 12 12 12	- 4.0mg 1.33 2.66 1.33 0.67 1.33 1.33 1.33	136.8±34.1 73.0±21.2** 92.9±34.6* 117.8±33.6## 96.5±25.9*# 97.1±19.1## 129.7±28.3##ψ& 128.4±23.6##ψψ&& 135.0±28.3##ψψ&&	126.3±53.2 75.6±23.9** 100.7±56.8 84.9±34.8* 77.2±32.1* 100.1±44.6 116.4±44.9#& 87.4±41.0 117.6±37.0##&

Annotate: compare * P＜0.05, * * P＜0.01 with the blank group; Compare #P＜0.05, ##P＜0.01 with the Ethylurethanm group; Compare ψ P＜0.05, ψ ψ P＜0.01 with the QINKAILING ZHUSHEYE group; Compare ﹠amp with dosage in the injection of the present invention; P＜0.05 ， ﹠amp; ﹠amp; P＜0.01.

Table 3 result shows, compares with the blank group, and 30mm, 60min all have obvious inhibitory action (P＜0.01) to spontaneous activity in mice after the administration of Western medicine positive drug Ethylurethanm group; Chinese medicine positive drug QINKAILING ZHUSHEYE group 30min behind medicine has inhibitory action (P＜0.05); Injection high dose group of the present invention has inhibitory action (P＜0.05) to spontaneous activity in mice 60min behind medicine; Dosage group 30min, 60min behind medicine all have inhibitory action (P＜0.05) in the injection of the present invention; Injection low dose group of the present invention is 30min, 60min inhibitory action no difference of science of statistics (P＞0.05) behind medicine; But the side's of tearing open puerarin injection group, baicalin for injection liquid group, taurine injection 30min, 60min behind medicine all do not have obvious inhibitory action (P＞0.01).With Western medicine positive drug Ethylurethanm group relatively, the basic, normal, high dosage group of injection of the present invention all after administration 30min all there were significant differences (P＜0.05), action intensity is lower than Western medicine positive drug Ethylurethanm group; The basic, normal, high dosage group of injection of the present invention 60min after administration does not have significant difference (P＞0.05), and action intensity is close with Western medicine positive drug Ethylurethanm group.Compare with the QINKAILING ZHUSHEYE group, the basic, normal, high dosage group of injection of the present invention is the equal no difference of science of statistics of each time point (the P value all＞0.05), and action intensity is close with Chinese medicine positive drug QINKAILING ZHUSHEYE group.The side of tearing open studies show that; compare with the blank group; the puerarin injection group; baicalin for injection liquid group; the taurine injection group does not all have remarkable sedation (P＞0.05), but the dosage group has remarkable sedation (P＜0.05) in the injection made from dosage of the present invention, points out three medicine compatibilities to use; produce new drug effect, three kinds of components compatibilities of prompting we have collaborative, potentiation.

3.4 discuss

Above result shows that each medicine all has in various degree sedation to normal mouse, wherein the medicine of quick acting has injection of the present invention, QINKAILING ZHUSHEYE, crow to draw sugar, injection high dose wherein of the present invention onset is slow slightly, and middle dose effect is held time than low dosage, QINKAILING ZHUSHEYE is long and quick acting.The puerarin injection onset is slow than dosage in the injection of the present invention in the side's of tearing open matched group, and baicalin for injection liquid and taurine injection have certain sedation, but with blank group no difference of science of statistics.Behind the medicine the same time respectively the sedation effect of the side's of tearing open matched group point out each compatibility composition of injection of the present invention on sedation, to have obvious role in synergism all less than dosage in the injection of the present invention.The 30min sedation effect is not obvious behind this experiment high dose group medicine, and the 1h effect is obvious behind the medicine, points out this dosage to be used for calm mice, and dosage is excessive.

4, the analgesic activity of injection of the present invention

Summary: utilize acetic acid mouse peritoneal injection, stimulate its pain and occur turning round embodying and resemble.After comparing different dosing group mouse peritoneal injection acetic acid, turn round the difference of the movable number of times of body, thereby judge the analgesic effect of injection of the present invention.

4.1 experiment purpose: study injection of the present invention analgesic effect

4.2 experiment material:

Positive control drug: indometacin, Weifang, Shandong Province pharmacy two factories, lot number: 050403; QINKAILING ZHUSHEYE: Pharmaceutical Factory of Beijing University of Chinese Medicine provides, authentication code: the accurate word Z11020269 of traditional Chinese medicines, batch number: 511208A.

Material and reagent: glacial acetic acid, chemical pure, Guangzhou Chemical Reagent Factory production, lot number: 0203428; Stopwatch

4.3 experimental technique and result:

Only get NIH mice 22～25g90; male and female half and half; be divided into 9 groups at random: blank group, indometacin positive controls, QINKAILING ZHUSHEYE positive controls; the basic, normal, high dosage of injection of the present invention (is calculated 10,20,40 times that are equivalent to clinical dosage by weight; the content of dispersion of middle dosage group baicalin is identical with QINKAILING ZHUSHEYE) group, puerarin injection group, baicalin for injection liquid group; the taurine injection group is except that the indometacin gastric infusion, and all the other each groups all adopt administered intramuscular.Dosage sees Table 1.Successive administration 7d, 30min after the last administration, the glacial acetic acid solution of every group every mouse peritoneal injection 0.5%, that counts out behind the injection glacial acetic acid mice in the 10min turns round the body number of times, and the time of embodying elephant appears turning round in record first.Turning round the body number of times and occurring turning round body time speed difference first of each treated animal of t check comparison has or not significance.The results are shown in Table 4.

The influence of table 4 injection xylol of the present invention induced mice auricle edema (x ± s)

Group	Number of animals (only)	Dosage (ml/kg)	Turn round the body number of times	Turn round the body time (second) first
Group	Number of animals (only)	Dosage (ml/kg)	Turn round the body number of times	Turn round the body time (second) first	Blank indometacin QINKAILING ZHUSHEYE injection of the present invention injection of the present invention injection of the present invention	10 10 10 10 10 10	- 4.0mg 1.33 0.67 1.33 2.66	32±14 7±5 22±15 8±9# 14±12** 16±11*$	144±64 365±123** 221±249 329±262 341±231* 357±288*

Baicalin for injection liquid puerarin injection taurine injection

10 10 10

1.33 1.33 1.33

18±4*$ 11±9** 16±2*

342±201* 399±328* 307±203

Annotate: compare * p＜0.05, * * p＜0.01 with the blank group; Compare with QINKAILING ZHUSHEYE: #p＜0.05, ##p＜0.01; Compare: $p＜0.05 ， $$p＜0.01 with indometacin; With dosage ， ﹠amp in the injection of the present invention; P＜0.05 ， ﹠amp; ﹠amp; P＜0.01

Table 4 result shows: compare with the blank group, Western medicine positive drug indometacin group is turned round the body number of times and occurs turning round the body time first that there were significant differences (P＜0.01), Chinese medicine positive drug QINKAILING ZHUSHEYE group is turned round the body number of times and occurred turning round the body time does not first then have significant difference (P＞0.05), occurs turning round the body time trend first but have to reduce to turn round the body number of times and prolong; The basic, normal, high dosage of injection of the present invention can reduce the number of times (P＜0.05) of the writhing response that mice pain causes, the effect of wherein low, middle dosage group is remarkable, the time that occurs first turning round body is with middle and high dosage group variant (P＜0.05), can delay the generation of the writhing response that mice pain causes; The side's of tearing open research; compare with the blank group; baicalin for injection liquid, taurine injection group occur turns round body time number average variant (P＜0.05); puerarin injection has utmost point significant difference (P＜0.01); baicalin for injection liquid, puerarin injection, taurine injection group illustrate that occurring turning round body also variant on the time (P＜0.05) first three kinds of compositions all are analgesic effective ingredient.Compare with indometacin, except that injection high dose of the present invention on turning round the body number of times variant, in other injection of the present invention, no matter low dosage administration group be to turn round the body number of times or turning round body equal no difference of science of statistics (P＞0.05) on the time first, analgesic activity intensity than low dosage time of prompting injection of the present invention is suitable with Western medicine positive drug indometacin group.Compare with the Chinese medicine positive control drug, the body number of times of turning round of injection low dose group of the present invention lacks than QINKAILING ZHUSHEYE, action intensity big (P＜0.05), no matter the middle and high dosage group of injection of the present invention is to turn round the body number of times or turning round body equal no difference of science of statistics (P＞0.05) on the time first, the action intensity and the QINKAILING ZHUSHEYE of prompting injection of the present invention are suitable, when low dosage even be better than QINKAILING ZHUSHEYE; With injection of the present invention relatively, each group of the side of tearing open reaches and occurs turning round body no difference of science of statistics (P＞0.05) on the time first turning round the body number of times, wherein with the best results of puerarin injection, three medicine compatibilities have synergism.

4.4 discuss

Above results suggest: injection 1. of the present invention has good analgesic effect, turns round the number of times analysis of body in the 10min and does not see into a certain amount of effect relationship, but analyze from turning round the body time first, and it is long more that the time that body occurs is turned round in the high more postponement of injection dosage of the present invention.2. from the side of tearing open contrast angle analysis, the puerarin analgesic activity is the strongest, and baicalin takes second place, after taurine is; Three's dosage is identical with dosage in the injection of the present invention, therefore can infer that each composition of injection of the present invention has certain synergistic function on analgesic activity.

5, the external anti-allergic effects of injection of the present invention

Summary: experimentize with reference to version in 1994 " the new drug pharmacological toxicology is learned the research guideline " the anaphylaxis contractile response of ileum flesh " sensitized guinea pig exsomatize ", comparative drug causes the inhibition degree of the stripped ileum flesh anaphylaxis contractile response of sensitized guinea pig to egg protein, thereby infers the antiallergic effect of injection of the present invention.

5.1 experiment purpose: study the antianaphylactic effect of injection of the present invention

5.2 experiment material

Be subjected to reagent: injection of the present invention is provided by Traditional Chinese Medicine University Of Guangzhou new drug development research center.

Positive control drug: QINKAILING ZHUSHEYE, Pharmaceutical Factory of Beijing University of Chinese Medicine produces, batch number: 511208A.Cyproheptadine hydrochloride, the 2mg/ sheet, Pharmaceutical Co Ltd, Changzhou Pharmaceutical Factory No.4 provides, lot number: KD9290

Material and reagent: egg protein (sigma company provides); K-H liquid (autogamy); BL-410 bio signal acquisition system, Tai Meng Electronics Co., Ltd. in Chengdu produces;

The side's of tearing open contrast medicine: puerarin injection, baicalin for injection liquid, taurine injection provides by Traditional Chinese Medicine University Of Guangzhou new drug development research center.

Laboratory animal: Cavia porcellus, regular grade, Traditional Chinese Medicine University Of Guangzhou's animal center provides.

5.3 experimental technique and result:

Get 10 of Cavia porcelluss, body weight 200～250g.Every each intramuscular injection 5% egg protein physiological salt liquid 0.4ml of Cavia porcellus two back legs, this solution of lumbar injection 1.0m is with sensitization simultaneously, after 3 weeks with the Cavia porcellus sacrificed by exsanguination, cut open the belly and fetch intestinal, be cut into 1cm left and right sides intestinal segment, insert in the bath that fills K-H liquid 20ml, an end is fixed on the fixation hook of bath bottom, the other end links to each other with tension transducer, record shrink tension (g).Preload 1～1.5g, 37 ± 1 ℃ of constant temperature begin experiment behind the balance 15min.Add following reagent normal saline (model group), cyproheptadine hydrochloride normal saline solution (positive controls), QINKAILING ZHUSHEYE (positive controls), injection of the present invention (being subjected to the reagent group), puerarin injection (side's of tearing open matched group), baicalin for injection liquid (side's of tearing open matched group), taurine injection (side's of tearing open matched group) toward bath respectively, each medicine final concentration sees Table 1.After treating medicine and specimen contacting 5min, in bath, add 5mg/ml egg protein K-H solution 0.1ml and carry out the antigen attack, respectively organize the difference of ileum shrink tension, respectively organize difference with the t check and have or not significance.The results are shown in Table 5.

The outer anti-allergic effects of table 5 injecting fluid of the present invention (x ± s)

Group	Number of animals (only)	Final concentration (ml/ml)	Contractility difference (g)
Group	Number of animals (only)	Final concentration (ml/ml)	Contractility difference (g)	Blank anarexol qingkailing injections parenteral solution of the present invention parenteral solution of the present invention parenteral solution baicalin for injection of the present invention liquid puerarin injection taurine injection	10 10 10 10 10 10 10 10 10	- 0.0045mg 0.01 0.005 0.01 0.015 0.01 0.01 0.01	0.72±0.32 0.15±0.10 0.27±0.16 0.36±0.28$ 0.26±0.15* 0.26±0.18k 0.18±0.15* 0.53±0.29#$$& 0.48±0.17##$$&&

Annotate: compare * p＜0.05, * * p＜0.01 with the blank group; Compare with QINKAILING ZHUSHEYE: #p＜0.05, ##p＜0.01; Compare: $p＜0.05 ， $$p＜0.01 with cyproheptadine hydrochloride; With dosage ， ﹠amp in the injection of the present invention; P＜0.05 ， ﹠amp; ﹠amp; P＜0.01

As can be seen from Table 5: compare with the blank group, Western medicine positive drug cyproheptadine hydrochloride, Chinese medicine positive drug QINKAILING ZHUSHEYE, the middle and high dosage group of injection of the present invention all have the effect (p＜0.01) that extremely significantly suppresses the intestinal segment contraction; Injection low dose group of the present invention, puerarin injection, taurine injection all have remarkable inhibitory action (p＜0.05).Compare with Western medicine positive drug cyproheptadine hydrochloride, the middle and high dosage group of injection of the present invention no difference of science of statistics (p＞0.05), injection low dose group of the present invention variant (p＜0.05) points out injection of the present invention middle and high dosage group action intensity close with Western medicine positive drug cyproheptadine hydrochloride.Compare with Chinese medicine positive drug QINKAILING ZHUSHEYE, the equal no difference of science of statistics of each dosage group of injection of the present invention (p＞0.05) points out each dosage group action intensity of injection of the present invention close with Chinese medicine positive drug QINKAILING ZHUSHEYE.Puerarin injection, taurine injection in the side's of tearing open group are with Chinese medicine positive drug QINKAILING ZHUSHEYE, Western medicine positive drug cyproheptadine hydrochloride more variant (p＜0.05 or p＜0.01); Compare with injection of the present invention; puerarin injection, taurine injection suppress the effect variant (p＜0.05 or p＜0.01) that anaphylaxis is shunk; baicalin for injection liquid is no difference of science of statistics (p＞0.05) then, and the prompting baicalin is the main effective ingredient of injection anti-allergic effects of the present invention.

5.4 discuss

Above results suggest: normal saline blank group can produce obvious contractile response after attacking the stripped ileum of sensitized guinea pig with antigen, QINKAILING ZHUSHEYE, cyproheptadine hydrochloride, injection of the present invention all have its anaphylaxis contractile response of remarkable inhibition, and injection of the present invention is a certain amount of effect relationship.The inhibitory action of each composition of injection is the strongest with baicalin, and occurs the part specimen and contractile response do not occur; It is not remarkable that taurine, puerarin suppress effect, points out injection ingredient of the present invention that antiallergic is had certain synergism.The intestinal segment anaphylaxis that injection of the present invention and QINKAILING ZHUSHEYE, cyproheptadine hydrochloride be the same to have due to the quick inhibition egg protein is shunk, and is expected to be used to alleviate I type allergy such as bronchial asthma, Anaphylaxis enteritis, urticaria clinically.

6, injection of the present invention is to the influence of mice swimming time

Summary: by measuring the length of administration mice swimming time, compare the swimming time difference between each administration group group, thereby judge the influence of injection of the present invention to mouse anti stress ability size.

6.1 experiment purpose: study injection of the present invention to promoting the influence of anti-stress ability.

6.2 experiment material:

Positive control drug: QINGCHUN BAO, the 0.3g/ grain, (lot number: 0403016), QINKAILING ZHUSHEYE: Pharmaceutical Factory of Beijing University of Chinese Medicine provides, authentication code: the accurate word Z11020269 of traditional Chinese medicines, batch number: 511208A in Zhengda Qingchunbao Pharmaceutical Co., Ltd.

The side's of tearing open contrast medicine: injection of the present invention, puerarin injection, baicalin for injection liquid, taurine injection provide by Traditional Chinese Medicine University Of Guangzhou new drug center.BS110S electronic balance: Sartorius company product.

Equipment: 50*30*25cm ³Glass jar, the heavy burden thing (1.8～2.8g), thermometer, stopwatch.

6.3 experimental technique and result:

Get 90 of mices; body weight is 18～22g; male and female half and half are divided into 9 groups at random: blank group, QINGCHUN BAO positive controls; the QINKAILING ZHUSHEYE positive controls; the basic, normal, high dosage of injection of the present invention (be 10,20,40 times of clinical dosage according to the weight, the content of dispersion of middle dosage group baicalin is identical with QINKAILING ZHUSHEYE) group, the puerarin injection group; baicalin for injection liquid group, the taurine injection group.Except that the QINGCHUN BAO gastric infusion, all the other each groups all adopt administered intramuscular.Dosage sees Table 1.Animal successive administration 7d, every day 1 time.1h after the last administration, weight in a mice body weight 10% of mouse tail bundle, respectively mice is put into the glass jar that depth of water 20cm, water temperature keep 20 ± 0.5 ℃, timing immediately, can not the person of emerging be with mouse head submerged 10s and stop timing when muscle power is exhausted, between institute's timing is the swimming time of mice, the results are shown in Table 6, respectively organizes swimming time with the t check and has or not diversity.

Table 6 injection of the present invention is to the influence of immune organ weight (x ± s)

Group	Number of animals (only)	Dosage (ml/kg)	Swimming time (second)
Group	Number of animals (only)	Dosage (ml/kg)	Swimming time (second)	Blank QINGCHUN BAO qingkailing injections parenteral solution of the present invention parenteral solution of the present invention parenteral solution baicalin for injection of the present invention liquid puerarin injection taurine injection	10 10 10 10 10 10 10 10 10	- 0.2g 1.33 0.67 1.33 2.66 1.33 1.33 1.33	223±65.1 335±91.0** 236±95.9$ 246±76.3$ 287.6±71.1* 365±171.5* 228±75.5$ 261±112.0 324±103.4*

Annotate: compare * p＜0.05, * * p＜0.01 with the blank group; Compare with QINKAILING ZHUSHEYE: #p＜0.05, ##p＜0.01; Compare: $p＜0.05 ， $$p＜0.01 with QINGCHUN BAO; With dosage ， ﹠amp in the injection of the present invention; P＜0.05 ， ﹠amp; ﹠amp; P＜0.01

Table 6 is the result show: with the blank group relatively, there were significant differences (p＜0.01) for Chinese medicine positive drug QINGCHUN BAO group, but QINKAILING ZHUSHEYE no difference of science of statistics (p＞0.05) then; The middle and high dosage of injection of the present invention variant (p＜0.05); Taurine injection also variant (p＜0.05) in the side's of tearing open group, all the other each groups all do not have statistical discrepancy with blank group; Prompting, positive drug QINGCHUN BAO, the middle and high dosage of injection of the present invention, taurine injection all can prolong the mice swimming time, improve the mouse anti stress ability; QINKAILING ZHUSHEYE does not show and prolongs the effect of mice swimming time.Compare with positive drug QINGCHUN BAO group, the middle and high dosage there was no significant difference of injection of the present invention points out injection of the present invention middle and high dosage group action intensity close with the positive drug QINGCHUN BAO.Compare with QINKAILING ZHUSHEYE, the basic, normal, high dosage group of injection of the present invention action intensity no difference of science of statistics (p＜0.05), but the middle and high dosage group of injection of the present invention action intensity all is better than QINKAILING ZHUSHEYE.Baicalin for injection liquid and positive drug QINGCHUN BAO group more variant (p＜0.05) in the side's of tearing open group; Compare with injection of the present invention; puerarin injection, taurine injection suppress the effect zero difference (p＞0.05) that anaphylaxis is shunk; but taurine injection is promoted the effect of animal anti-stress ability and is better than injection of the present invention; the prompting taurine injection is the main effective ingredient that injection of the present invention is promoted the animal anti-stress ability, and baicalin, puerarin are promoted the synergism that has of animal anti-stress ability in injection of the present invention.

6.4 discuss:

As can be seen from the above results: QINKAILING ZHUSHEYE is to promoting the DeGrain of animal anti-stress ability, and QINGCHUN BAO then effect is remarkable; Injection of the present invention is a certain amount of effect relationship, and the middle and high dosage group effect of injection of the present invention is also obvious, though compare no difference of science of statistics with QINKAILING ZHUSHEYE, the effect of promoting the animal anti-stress ability is better than QINKAILING ZHUSHEYE; Have only the effect of taurine injection obvious in the side's of tearing open matched group, point out in the injection of the present invention each composition to have certain synergism strengthening on the animal anti-stress ability.

7, injection of the present invention is to the influence of mononuclear phagocyte phagocytic function

Summary: immunosuppressant can reduce the phagocytic function of mononuclear phagocyte, on the contrary immunostimulant effect then.This experiment is by the influence of research medicine to the cytophagous phagocytic function of mouse monokaryon, thereby judgement bovine bezoar injection liquid is to Immune Effects.

7.1 experiment purpose: study injection of the present invention to Immune Effects.

7.2 experiment material:

Be subjected to reagent: injection of the present invention, Traditional Chinese Medicine University Of Guangzhou new drug development research center provides.

Positive control drug: prednisolone acetate, the 5mg/ sheet, Guangdong Huanan Pharmaceutical Co., Ltd produces, lot number: 050301; QINKAILING ZHUSHEYE: Pharmaceutical Factory of Beijing University of Chinese Medicine produces, batch number: 511208A.

The side's of tearing open contrast medicine: baicalin for injection liquid, puerarin injection, taurine injection provide by Traditional Chinese Medicine University Of Guangzhou new drug center.

Equipment: 10S electronic balance: Sartorius company product; 722 grating spectrophotometers, Shanghai Precision Scientific Apparatus Co., Ltd produces; China's prepared Chinese ink

7.3 experimental technique and result:

Get 90 of mices; body weight is 18～22g; male and female half and half are divided into 9 groups at random: blank group, prednisolone acetate positive controls; the QINKAILING ZHUSHEYE positive controls; the basic, normal, high dosage of injection of the present invention (press 10,20,40 times for clinical dosage of body weight and calculation, the content of dispersion of middle dosage group baicalin is identical with QINKAILING ZHUSHEYE) group, the puerarin injection group; baicalin for injection liquid group, the taurine injection group.Except that the prednisolone acetate gastric infusion, all the other each groups all adopt administered intramuscular.Dosage sees Table 2., animal successive administration 7 days, every day 1 time.After the last administration 0.5 hour, tail vein injection China prepared Chinese ink (with 2 times of physiological salt liquid dilutions) 0.1ml/10g, 2min and 12min after injecting prepared Chinese ink get blood 20 μ l with special suction pipe from the mouse orbit rear vein beard, are blown into 0.1%Na at once ₂CO ₃Among the solution 3ml, suction pipe sucks to blow out in this liquid and fully washes out the blood that the suction pipe wall adheres to for several times, is dissolved in 10ml0.1%Na with 0.025ml normal mouse blood ₂CO ₃Trap (D) value is measured in solution school zero in the 675nm place, calculate phagocytic index K.

K = \frac{\log OD 1 - \log OD 2}{t 2 - t 1}

The results are shown in Table 7.

Table 7 injection of the present invention is to the influence of mononuclear phagocyte phagocytic function (x ± s)

Group	Animal number of elements (only)	Dosage (ml/kg)	Clean up index K (h-1)
Group	Animal number of elements (only)	Dosage (ml/kg)	Clean up index K (h-1)	Blank prednisone acetate qingkailing injections parenteral solution of the present invention parenteral solution of the present invention parenteral solution baicalin for injection of the present invention liquid puerarin injection taurine injection	10 10 10 10 10 10 10 10 10	- 4.0mg 1.33 0.67 1.33 2.66 1.33 1.33 1.33	0.98±0.23 0.79±0.17* 0.95±0.26 1.20±0.32$$ 1.29±0.40#$$ 1.34±0.29##$$ 0.99±0.19& 1.42±0.49#$$ 0.96±0.36

Annotate: compare * p＜0.05, * * p＜0.01 with the blank group; Compare with QINKAILING ZHUSHEYE: #p＜0.05, ##p＜0.01; Compare: $p＜0.05 ， $$p＜0.01 with prednisolone acetate; With dosage ， ﹠amp in the injection of the present invention; P＜0.05 ， ﹠amp; ﹠amp; P＜0.01

Table 7 result shows: with the blank group relatively, Western medicine positive drug prednisolone acetate group reduces the cytophagous phagocytic function of mice (p＜0.01), but Chinese medicine positive drug QINKAILING ZHUSHEYE no difference of science of statistics (p＞0.05) then; The basic, normal, high dosage of injection of the present invention can strengthen the cytophagous phagocytic function of mice, and wherein high dose has utmost point significant difference (P＜0.01), and also there were significant differences for middle dosage (p＜0.05); The side's of tearing open group puerarin injection variant (p＜0.05); Prompting, prednisolone acetate can suppress the cytophagous phagocytic function of mice, reduces function of immune system; The middle and high dosage of injection of the present invention, puerarin injection all can strengthen the cytophagous phagocytic function of mice, improve function of immune system; QINKAILING ZHUSHEYE does not show the function of immune system influence.Tear Fang Zuzhong open, baicalin for injection liquid and taurine injection and blank group be not more to the cytophagous phagocytic function influence of mice (P＞0.05), and puerarin injection can significantly strengthen the cytophagous phagocytic function of mice, improves function of immune system; The prompting puerarin is the main effective ingredient that injection of the present invention improves the effect of mouse immune systemic-function.

7.4 discuss

As can be seen from the above results: injection 1. of the present invention has the cytophagous phagocytic function of the mouse monokaryon of promotion, points out it to have the effect that improves immunologic function, and is certain dose-effect relationship.2. from the side's of tearing open compatibility angle analysis, the effect of puerarin raise immunity is the strongest, and baicalin takes second place, and after taurine was, triplicity had certain synergism; 3. the injection of the present invention of Isodose obviously is better than QINKAILING ZHUSHEYE to promoting the cytophagous phagocytic function effect of mouse monokaryon.

8, injection of the present invention is to the protective effect of immunologic liver injury

Summary: utilize the canavaline intravenous injection to cause the chmice acute immunologic liver injury, observe the protective effect of medicine to mouse liver injury; By calculating the organ coefficient of liver, spleen, thymus, detect the content of AST, ALT, SOD, MDA, judge the protective effect of medicine to the chmice acute immunologic liver injury.

8.1 experiment purpose: study the protective effect of injection of the present invention to acute immunologic liver injury.

8.2 experiment material:

Positive control drug: bifendate drop pill: Beijing XieHe medicine Factory's product, lot number: 04060107

Material and reagent: AST, ALT, SOD, MDA test kit are purchased and are built up biological study institute, lot number: 20050707 in Nanjing; LDZ5 type centrifuge (Beijing Medical Centrifugal Machine Factory); 722 grating spectrophotometer (Shanghai Precision Scientific Apparatus Co., Ltd

8.3 experimental technique and result:

Only get NIH mice 18～22g48, male and female half and half, be divided into 4 groups at random: blank group, model group, the bifendate positive controls, dosage in the injection of the present invention (calculating 20 times that are equivalent to clinical dosage by weight) group, injection administered intramuscular of the present invention, the bifendate gastric infusion, dosage sees Table 1.Successive administration 3d, the 4th day morning be every mouse tail vein injection canavaline 16mg/kg except that the blank group,, after modeling and continue that afternoon, second day afternoon administration.4h after the last administration, model group and the disposable tail vein injection canavaline of each Mus of administration group 16mg/kg.Mice is plucked eyeball and gets blood behind the 12h, and separation of serum is used to detect AST, ALT, dissects to get liver, spleen, thymus and weigh, and calculates organ coefficient, gets part liver tissue homogenate and detects SOD, MDA.The content difference of the organ coefficient of each treated animal liver of t check comparison, spleen, thymus, AST, ALT, SOD, MDA has or not significance.The results are shown in Table 8,9.

Table 8 injection of the present invention is to the protective effect of mouse immune liver damage (x ± s)

Group	Number of animals (only)	Dosage (ml/kg)	The liver coefficient	The spleen coefficient	The thymus coefficient
Group	Number of animals (only)	Dosage (ml/kg)	The liver coefficient	The spleen coefficient	The thymus coefficient	Blank model bifendate injection of the present invention	10 10 10 10	- - 60mg 1.33	4.8±0.3 6.7±0.6 6.2±0.6# 6.1±0.6**#	0.5±0.1 0.8±0.2 0.7±0.2 0.9±0.1**	0.4±0.1 0.3±0.1* 0.3±0.1* 0.2±0.1**#

Table 9

Group	Dosage (ml/kg)	AST	ALT	SOD	MDA
Group	Dosage (ml/kg)	AST	ALT	SOD	MDA	Blank model	- -	309.6±71.2 731.1±161.1**	148.3±35.6 274.1±51.4**	25.8±5.1 20.9±4.6*	16.5±6.4 26.6±6.4**

Bifendate injection of the present invention

60mg 1.33

535.0±81.7**# 541.7±111.7**##

143.6±42.2# 208.5±55.2*##

28.1±4.7## 27.6±7.5#

14.7±3.9## 17.3±4.6##

Annotate: compare * p＜0.05, * * p＜0.01 with the blank group; Compare with model group: #p＜0.05, ##p＜0.01; Compare ， $p＜0.05 ， $$p＜0.01 with bifendate

Table 8,9 results show: compare with the blank group, the basic and blank group of the every index of model group is variant, points out this experimental animal model to make and touches successfully; Compare positive control drug bifendate and the every index of injection group of the present invention all variant except that the spleen coefficient (p＜0.05) with model group; And compare the every index no difference of science of statistics of injection of the present invention (p＞0.05) with the positive control drug bifendate; Except that SOD, MDA index, other administration group detects the basic and blank group variant (p＜0.05) of index (liver coefficient, spleen coefficient, thymus coefficient, AST, ALT); Intravenous injection causes the chmice acute immunologic liver injury certain protection effect is arranged to canavaline to point out injection of the present invention, and action intensity is identical with the positive control drug bifendate, and the SOD of immunologic liver injury mice, MDA index can return to blank group of level.

8.4 discuss

As can be seen from the above results: the basic and blank group of every detection index of model group is variant, liver, splenomegaly, and serum transaminase concentration raises, and organizes the peroxidating product to increase, and shows this modeling method success, can cause the chmice acute hepatic injury; After the hepatic injury mice gives bifendate and injection of the present invention, can reduce the enlargement degree of liver, spleen etc., reduce AST, ALT content in the serum, SOD is lower than model group than model group height, MDA in the tissue, show medicine have protect the liver, the anti-peroxidation effect; Simultaneously, injection of the present invention every detection index result and bifendate no difference of science of statistics show that injection of the present invention has good the liver protecting and ALT lowering effect.

9, the compound bovine bezoar injection is to the influence of mouse skin delayed hypersensitivity

Summary: the research medicine is to the influence of mouse skin delayed hypersensitivity.Utilize dinitrochlorobenzene (DSCB) to smear mouse skin and make its sensitization, give sensitized mice normal saline, the compound bovine bezoar injection of three kinds of various dose, QINKAILING ZHUSHEYE, cyproheptadine hydrochloride respectively; Attack mice one exterior feature of picking up the ears with DSCB again behind the 10d, make its auricle produce DCHR.By the weight differential that micrometric measurement antigen is attacked back two ears, the anaphylaxis degree of comparison model group, administration group mice, thus judge the influence of injection to the mouse skin delayed hypersensitivity.

Experiment purpose: research compound bovine bezoar injection is to the influence of mouse skin delayed hypersensitivity.

9.1 experiment material:

Be subjected to reagent: the compound bovine bezoar injection, Traditional Chinese Medicine University Of Guangzhou new drug development research center provides

Positive control drug: cyproheptadine hydrochloride, 2mg/ sheet, Pharmaceutical Co Ltd, Changzhou Pharmaceutical Factory No.4, lot number: KD9290.

QINKAILING ZHUSHEYE: Pharmaceutical Factory of Beijing University of Chinese Medicine provides, authentication code: the accurate word Z11020269 of traditional Chinese medicines, batch number: 511208A.

Reagent: dinitrochlorobenzene (DSCB), Nanxiang Reagent Co., Ltd., Shanghai produces.

9.2 experimental technique and result:

Get NIH mice 22～25g; 118; male and female half and half are divided into 9 groups at random: model group, cyproheptadine hydrochloride positive controls; the QINKAILING ZHUSHEYE positive controls; the basic, normal, high dosage group of compound bovine bezoar injection (be equivalent to 10,20,40 times of clinical dosage according to the weight, the dosage of middle dosage group is identical with QINKAILING ZHUSHEYE), the puerarin injection group; baicalin for injection liquid group, the taurine injection group.With 5% 2,4-dinitro-chlorine phenethanol liquid coats mouse part skin (unhairing) sensitization, sensitization administration the previous day, outside the demineralizing acid Cyproheptadine gastric infusion, all the other all adopt intramuscular injection, dosage sees Table 1, once a day, continuous 9 days.Be coated with auris dextra with 1% 2,4 dinitrochlorobenzene on the 7th day after the sensitization, put to death mice behind the 24h, the clip auricle is weighed, with about two auricle weight differences as the delayed hypersensitivity value, the results are shown in Table 10.

Table 10 compound bovine bezoar injection is to the influence of mouse skin delayed hypersensitivity (x ± s)

Group	The animal number of elements	Dosage (ml/kg)	Two ear weight differentials (mg)
Group	The animal number of elements	Dosage (ml/kg)	Two ear weight differentials (mg)	Model group anarexol qingkailing injections compound bovine bezoar parenteral solution compound bovine bezoar parenteral solution compound bovine bezoar parenteral solution baicalin for injection liquid puerarin injection taurine injection	12 12 12 12 12 12 12 12 12	- 4.0mg 1.33 2.67 1.33 0.67 1.33 1.33 1.33	1.0±0.5 0.3±0.2 0.7±0.5# 0.4±0.2 0.6±0.4* 0.9±0.5## 0.9±0.5## 0.5±0.2*# 0.7±0.4#

Annotate: compare * P＜0.05, * * P＜0.01 with model group; Compare #P＜0.05, ##P＜0.01 with the cyproheptadine hydrochloride group; Compare ψ P＜0.05, ψ ψ P＜0.01 with the QINKAILING ZHUSHEYE group; Compare ﹠amp with dosage in the compound bovine bezoar injection; P＜0.05 ， ﹠amp; ﹠amp; P＜0.01.

Table 10 result shows, compares with model group, and delayed hypersensitivity has obvious inhibitory action (P＜0.01) to Western medicine positive drug cyproheptadine hydrochloride to mouse skin; Delayed hypersensitivity has inhibitory action (P＜0.01, P＜0.05) to mouse skin for compound bovine bezoar injection height, middle dosage group.Compare with the cyproheptadine hydrochloride group, compound bovine bezoar injection height, middle dosage group do not have significant difference (P＞0.05); Chinese medicine positive drug QINKAILING ZHUSHEYE group, compound bovine bezoar injection low dose group, puerarin injection group, baicalin for injection liquid group, the taurine injection group is on the inhibitory action that mouse skin is produced delayed hypersensitivity all variant (P＜0.05); Prompting compound bovine bezoar injection height, middle dosage group are similar to Western medicine positive drug cyproheptadine hydrochloride on action intensity, and other administration group action intensities are lower than cyproheptadine hydrochloride.Compare with the QINKAILING ZHUSHEYE group, the equal no difference of science of statistics of the basic, normal, high dosage group of compound bovine bezoar injection (P＞0.05), but action intensity is better than the QINKAILING ZHUSHEYE group.The side of tearing open studies show that, delayed hypersensitivity has inhibitory action (P＜0.05) to the puerarin injection group to mouse skin, baicalin for injection liquid group, taurine injection group all do not have remarkable effect (P＞0.05), but also can suppress the mouse skin delayed hypersensitivity to a certain extent; Compare with dosage group in the compound bovine bezoar injection; puerarin injection group, baicalin for injection liquid group, taurine injection group all do not have significant difference (the P value all＞0.05); but puerarin injection group action intensity is better than middle dosage group, and the prompting puerarin is for suppressing the main effective ingredient of mouse skin delayed hypersensitivity.

9.4 discuss

Above result shows that each medicine has the effect that mouse skin produces delayed hypersensitivity that suppresses; significantly inhibiting be cyproheptadine hydrochloride group and compound bovine bezoar injection high dose group are wherein arranged; though dosage group, puerarin injection, taurine injection and model group no difference of science of statistics have inhibitory action in various degree in QINKAILING ZHUSHEYE, the compound bovine bezoar injection.From the inhibitory action of the side's of tearing open matched group,

10, carbon tetrachloride is caused the protective effect of chmice acute hepatic injury

Summary: inquire into the protective effect of injection of the present invention to carbon tetrachloride induced mice acute liver damage.Use CCl ₄Inducing mouse acute liver damage model is divided into blank group (being the normal control group), CCl with experiment mice ₄Model group, Western medicine bifendate matched group, Chinese medicine QINGKAILING matched group, injection of the present invention (basic, normal, high dosage) are organized, the side's of tearing open matched group (baicalin for injection liquid, puerarin injection, taurine injection).Respectively organize the glutamate pyruvate transaminase (ALT) in the mice serum, the content of glutamic oxaloacetic transaminase, GOT (AST) by detecting, observe liver, spleen, thymus index variation, thereby judge the protective effect of injection of the present invention carbon tetrachloride induced mice acute liver damage.

10.1 experiment purpose: study the protective effect of injection of the present invention to carbon tetrachloride induced mice acute liver damage.

10.2 experiment material:

Positive control drug: bifendate drop pill: Beijing XieHe medicine Factory's product, lot number: 04060107.QINKAILING ZHUSHEYE: Pharmaceutical Factory of Beijing University of Chinese Medicine produces, batch number: 511208A.

Material and reagent: AST, ALT, SOD, MDA test kit are purchased and are built up biological study institute, lot number: 20050707 in Nanjing; LDZ5 type centrifuge (Beijing Medical Centrifugal Machine Factory); 722 grating spectrophotometer (Shanghai Precision Scientific Apparatus Co., Ltd; Carbon tetrachloride, Guangzhou Chemical Reagent Factory production; Edible peanut oil, Wei Wei Food Co., Ltd in Dongguan produces

10.3 experimental technique and result:

Only get NIH male mice 22～25g100, be divided into 10 groups at random: blank group, model group; the bifendate positive controls, QINGKAILING positive controls, the basic, normal, high dosage group of injection of the present invention; baicalin for injection liquid group, puerarin injection group, taurine injection group.Remove the bifendate gastric infusion, other respectively organizes equal administered intramuscular, and blank group and model group give isometric normal saline.Dosage sees Table 1, successive administration 7d, water is can't help in animal fasting in the 7th day, and after the most last 1 administration 2h, except that the blank group gavaged Oleum Arachidis hypogaeae semen 10mL/kg, all the other each group all gavaged 0.10%CCl ₄Peanut oil solution 20mL/kg,

Overnight fasting.The blood sampling of 24h posterior orbit venous plexus, separation of serum detects the value of ALT, AST; Cut open the belly and take out liver, spleen, thymus, inhale the liquid of dehematizing, cut off fat, mesentery, the weight of the liver of accurately weighing, spleen, thymus.T check relatively each treated animal liver, spleen, the organ coefficient of thymus, the content difference of AST, ALT has or not significance.The results are shown in Table 11.

Table 11 injection of the present invention is to the protective effect of carbon tetrachloride induced mice acute liver damage (x ± s)

Group	Number of animals (only)	Dosage (ml/kg)	The liver coefficient	AST value (U/L)	ALT value (U/L)
Group	Number of animals (only)	Dosage (ml/kg)	The liver coefficient	AST value (U/L)	ALT value (U/L)	Blank model DDB qingkailing injections parenteral solution of the present invention parenteral solution of the present invention parenteral solution baicalin for injection of the present invention liquid puerarin injection taurine injection	10 10 10 10 10 10 10 10 10 10	- - 60mg 1.33 0.67 1.33 2.66 1.33 1.33 1.33	4.05±0.48 5.43±0.47* 4.87±0.57△△ 4.80±0.57△△ 5.31±0.47△ 4.96±0.32△ 4.77±0.24△△ 4.81±0.28△△ 4.81±0.27**△△ 4.18±0.55△△#$$&&	110.3±40.2 570.7±279.4 115.2±27.2△△ 316.9±61.3△ 230.9±105.5△△## 106.5±26.7△△$$ 96.5±53.8△△$$ 230.9±105.5△##$ 267.9±93.5△△##&& 242.5±96.4**△##&&	33.5±3.2 837.6±282.7** 107.7±67.3△△ 38.8±5.2△△ 47.6±13.1△△# 44.6±7.5△△#$ 34.2±5.2△△# 47.6±13.1*△△# 56.4±25.8△△ 59.3±14.8**△△$$&&

Annotate: compare * p＜0.05, * * p＜0.01 with the blank group; Compare with model group: △ p＜0.05, △ △ p＜0.01; Compare #p＜0.05, ##p＜0.01 with bifendate; Compare ， $p＜0.05 ， $$p＜0.01 with QINKAILING ZHUSHEYE: compare ， ﹠amp with dosage in the injection of the present invention; P＜0.05 ， ﹠amp; ﹠amp; P＜0.01.

Table 11 result shows: compare with the blank group, model group mouse liver coefficient, Serum ALT value, the every index of AST value are all organized variant (p＜0.05) with blank, prompting modeling success.Compare with model group, Western medicine positive drug bifendate, Chinese medicine positive drug QINKAILING ZHUSHEYE group mouse liver coefficient, Serum ALT value, AST value index all variant (p＜0.05) illustrate that bifendate and QINKAILING ZHUSHEYE all can reduce CCl ₄Due to acute liver damage mouse liver coefficient, Serum ALT value, the every index of AST value, to CCl ₄Due to the acute liver damage mice certain protective role is arranged; Each dosage group liver coefficient of injection of the present invention, Serum ALT value, AST value index all variant (p＜0.05) point out injection of the present invention to CCl ₄Due to the acute liver damage mice certain protective role is also arranged, and have tangible dose-effect relationship in liver coefficient, Serum ALT value, three indexs of AST value.Compare with the blank group, Western medicine positive drug bifendate group mice serum AST value index zero difference (p＞0.05), the prompting bifendate can reduce CCl ₄Due to dosage form hepatic injury mice AST value index to normal level; Injection group Serum ALT value of the present invention, AST value index zero difference (p＞0.05) point out injection of the present invention can reduce CCl ₄Due to dosage form hepatic injury mice serum ALT value, AST value index to normal level.Compare with Western medicine positive drug bifendate group, the basic no difference of science of statistics of the every index of injection various dose of the present invention (p＞0.05) points out injection of the present invention to CCl ₄Due to the protective effect of dosage form hepatic injury mice similar to bifendate, wherein effect of high dosage intensity is better than bifendate, each dosage group mice serum AST index of injection of the present invention all is better than the bifendate group.Compare with Chinese medicine positive drug QINKAILING ZHUSHEYE, the middle and high dosage serum of injection of the present invention AST value index all variant (p＜0.05) points out injection of the present invention that mice serum AST value index action intensity is better than QINKAILING ZHUSHEYE.Puerarin injection, taurine injection, baicalin for injection liquid and model group compare in the side's of tearing open group, liver coefficient, Serum ALT value, the equal significant difference of the every index of AST value (p＜0.05), and the prompting respectively side of tearing open is organized CCl ₄Due to the acute liver damage mice certain protective role is all arranged; Compare taurine injection group liver coefficient, Serum ALT value, AST value index all variant (p＜0.05 or p＜0.01) with dosage in the injection of the present invention; Puerarin injection group AST value index variant (p＜0.05); Baicalin for injection liquid is no difference of science of statistics (p＞0.05) then; But respectively the side's of tearing open group is to CCl ₄Due to acute liver damage mice protective effect intensity all be lower than injection of the present invention, point out injection three medicine compatibilities of the present invention to use, drug effect strengthens, three kinds of components compatibilities of prompting we have collaborative, potentiation.

10.4 discuss

As can be seen from the above results: the basic and blank group of every detection index of model group is variant, hepatomegaly, and serum transaminase concentration significantly raises, and shows this modeling method success, can cause the chmice acute hepatic injury; Give bifendate, QINKAILING ZHUSHEYE, injection of the present invention, baicalin for injection liquid, puerarin injection, taurine injection and carry out the protectiveness administration, can reduce the enlargement degree of liver, spleen etc., reduce AST, ALT content in the serum, show medicine have protect the liver, effect of reducing enzyme levels; Simultaneously, the every detection index of injection of the present invention result is better than bifendate and QINKAILING ZHUSHEYE, shows that injection of the present invention has good the liver protecting and ALT lowering effect, can improve the acute liver damage that the chemical reagent carbon tetrachloride causes.

11, to the protective effect of chmice acute alcoholic liver injury

Summary: inquire into the protective effect of injection of the present invention to ethanol induced mice acute liver damage.Experiment mice is divided into blank group (being the normal control group), ethanol model group, Western medicine bifendate matched group, Chinese medicine QINGKAILING matched group, injection of the present invention (basic, normal, high dosage) are organized, the side's of tearing open matched group (baicalin for injection liquid, puerarin injection, taurine injection); each group was taked the protectiveness successive administration seven days, caused the chmice acute hepatic injury with disposable the gavaging of 60% ethanol after the last administration.After detecting modeling, respectively organize the glutamate pyruvate transaminase (ALT) in the mice serum, the content of glutamic oxaloacetic transaminase, GOT (AST), observe liver, spleen, thymus index variation, thereby judge the protective effect of injection of the present invention ethanol induced mice acute liver damage.

11.1 experiment purpose: study the protective effect of injection of the present invention to ethanol carbon induced mice acute liver damage.

11.2 experiment material:

Material and reagent: AST, ALT, SOD, MDA test kit are purchased and are built up biological study institute, lot number: 20050707 in Nanjing; LDZ5 type centrifuge (Beijing Medical Centrifugal Machine Factory); 722 grating spectrophotometer (Shanghai Precision Scientific Apparatus Co., Ltd; Dehydrated alcohol, Guangzhou Chemical Reagent Factory provides.

11.3 experimental technique and result:

Only get NIH mice 22～25g100; male and female half and half; be divided into 10 groups at random: blank group; model group; the bifendate positive controls, QINGKAILING positive controls, the basic, normal, high dosage group of injection of the present invention (be equivalent to according to the weight clinical dosage 10,20,40 times); baicalin for injection liquid group, puerarin injection group, taurine injection group.Remove the bifendate gastric infusion, it respectively organizes equal administered intramuscular, and blank group and model group give isometric normal saline.Dosage sees Table 1, successive administration 7d, water is can't help in animal fasting in the 7th day, and after the most last 1 administration 2h, except that the blank group such as gavaged at the normal saline of capacity, all the other each groups all gavaged 60% alcoholic solution 20mL/kg, continue fasting.The blood sampling of 12h posterior orbit venous plexus, separation of serum detects the value of ALT, AST; Cut open the belly and take out liver, spleen, thymus, inhale the liquid of dehematizing, cut off fat, mesentery, the weight of the liver of accurately weighing, spleen, thymus.T check relatively each treated animal liver, spleen, the organ coefficient of thymus, the content difference of AST, ALT has or not significance.The results are shown in Table 12.

Table 12 injection of the present invention is to the protective effect of ethanol induced mice acute liver damage (x ± s)

Group	Number of animals (only)	Dosage (ml/kg)	The liver coefficient	AST value (U/L)	ALT value (U/L)
Group	Number of animals (only)	Dosage (ml/kg)	The liver coefficient	AST value (U/L)	ALT value (U/L)	Blank model DDB qingkailing injections parenteral solution of the present invention parenteral solution of the present invention parenteral solution baicalin for injection of the present invention liquid puerarin injection taurine injection	10 10 10 10 10 10 10 10 10 10	- - 60mg 1.33 0.67 1.33 2.66 1.33 1.33 1.33	4.21±0.40 6.00±0.41 4.35±0.33△△ 4.67±0.23△△ 4.11±0.27△△$$ 4.19±0.29△△$$ 4.23±0.24△△$$ 4.22±0.24△△$$ 4.14±0.19△△$$ 3.95±0.25△△#$$	53.8±19.6 488.6±216.1 136.9±100.2△△ 64.2±18.5△△ 58.1±13.3△△ 29.0±6.22△△#$$ 66.8±11.2△△ 72.0±13.3△△&& 60.9±13.6△△&& 94.3±31.0*△△$&&	25.6±11.6 330.8±132.0** 89.8±67.3△△ 29.5±19.2△△ 30.1±13.8△△# 26.7±7.5△△# 19.7±6.2△△# 35.2±6.4△△#& 44.2±15.1△△#& 161.3±88.1*△△&&

Annotate: compare * p＜0.05, * * p＜0.01 with the blank group; Compare with model group: △ p＜0.05, △ △ p＜0.01; Compare #p＜0.05, ##p＜0.01 with bifendate; Compare ， $p＜0.05 ， $$p＜0.01 with QINKAILING ZHUSHEYE; Compare ， ﹠amp with dosage in the injection of the present invention; P＜0.05 ， ﹠amp; ﹠amp; P＜0.01.

Table 12 result shows: compare with the blank group, model group mouse liver coefficient, Serum ALT value, the every index of AST value are all organized variant (p＜0.05) with blank, prompting modeling success.Compare with model group, Western medicine positive drug bifendate, Chinese medicine positive drug QINKAILING ZHUSHEYE group mouse liver coefficient, Serum ALT value, AST value index all have utmost point significant difference (p＜0.05), illustrate that bifendate and QINKAILING ZHUSHEYE all can significantly reduce acute liver damage mouse liver coefficient due to the ethanol, Serum ALT value, the every index of AST value, acute liver damage mice due to the ethanol is had good protective action; Each dosage group of injection of the present invention; liver coefficient, Serum ALT value, AST value index all have utmost point significant difference (p＜0.05); point out injection of the present invention that acute liver damage mice due to the ethanol is also had the good protection effect, and have tangible dose-effect relationship in liver coefficient index.With the blank group relatively, the equal zero difference of the every index of Western medicine positive drug bifendate group (p＞0.05), prompting bifendate can reduce due to the ethanol each index of dosage form hepatic injury mice to normal level; Chinese medicine positive drug QINKAILING ZHUSHEYE mice serum ALT value, AST value index zero difference (p＞0.05), the prompting QINKAILING ZHUSHEYE can reduce dosage form hepatic injury mice serum ALT value due to the ethanol, AST value index to normal level; The every index zero difference of injection group of the present invention (p＞0.05) points out injection of the present invention can reduce due to the ethanol the every index of dosage form hepatic injury mice to normal level.Compare with Western medicine positive drug bifendate group; injection various dose mice serum ALT value index of the present invention all variant (p＜0.05); other index zero difference; point out injection of the present invention similar to bifendate, wherein ALT value index action intensity is better than the bifendate group dosage form hepatic injury mice protective effect due to the ethanol.Compare with Chinese medicine positive drug QINKAILING ZHUSHEYE, injection liver coefficient index of the present invention all variant (p＜0.05) points out injection of the present invention that liver coefficient index action intensity is better than QINKAILING ZHUSHEYE.Puerarin injection, taurine injection, baicalin for injection liquid and model group are relatively in the side's of tearing open group, liver coefficient, Serum ALT value, the equal significant difference of the every index of AST value (p＜0.05), the prompting respectively side of tearing open are organized acute liver damage mice due to the ethanol are all had certain protective role; Compare taurine injection, puerarin injection, baicalin for injection liquid group Serum ALT value, AST value index all variant (p＜0.05 or p＜0.01) with dosage in the injection of the present invention; The prompting respectively side of tearing open group all is lower than injection of the present invention to acute liver damage mice protective effect intensity due to the ethanol, and injection three medicine compatibilities of the present invention are used, and drug effect strengthens, and the our three kinds of components compatibilities of prompting have collaborative, potentiation.

11.4 discuss

As can be seen from the above results: the basic and blank group of every detection index of model group is variant, liver, splenomegaly, and serum transaminase concentration significantly raises, and shows this modeling method success, can cause the chmice acute hepatic injury; Give bifendate, QINKAILING ZHUSHEYE, injection of the present invention, baicalin for injection liquid, puerarin injection, taurine injection and carry out the protectiveness administration, can reduce the enlargement degree of liver that ethanol causes, spleen etc., reduce AST, ALT content in the serum, show medicine have protect the liver, effect of reducing enzyme levels; Simultaneously, injection of the present invention every detection index result and bifendate no difference of science of statistics, hepatoprotective effect is better than QINKAILING ZHUSHEYE substantially, shows that injection of the present invention has good the liver protecting and ALT lowering effect, the acute liver damage that can prevent ethanol to cause.

12, compound recipe cattle sulphur injection hemolytic test report

12.1 material

12.1.1 be subjected to the reagent thing

Compound recipe cattle sulphur injection provides lot number by Traditional Chinese Medicine University Of Guangzhou new drug development research center: 20050809.

12.1.2 laboratory animal

1 of Beagle dog (9.0kg ♀) is by-------------institute Beagle dog plant provides the quality certification number, the moving word------------of doctor.17～20 ℃ of room temperatures, relative humidity 60%～68%.

12.1.3 reagent, instrument

Sodium chloride injection, lot number: 030701, the concentric pharmaceutical Co. Ltd of the strange power in Sichuan Province produces; XLJ-II type centrifugal precipitation mechanism, Shanghai medical apparatus factory; Small-sized three use constant water bath box, Beijing Medical Equipment Plant.

12.2 method

Adopt Beagle dog forelimb venous blood 10ml, remove in the cone-shaped glass bottle with the glass ball and to defibrinate, place in the graduated centrifuge tube, add the proper amount of sodium chloride injection, with 2000 rev/mins centrifugal 10 minutes, discard liquid, add chlorination sodium injection mixing, centrifugal again, so cyclic washing is gone up liquid to centrifugal back and is till the water white transparency, and the gained erythrocyte is prepared into 2% red cell suspension with sodium chloride injection.Get 7 test tubes and add amount of liquid medicine by table 1, add the chlorination sodium injection again to total amount 2.5ml, mix with 2% red cell suspension 2.5ml, each pipe shakes up, be placed in 37 ℃ of thermostatic water tanks, respectively at 15,30,60 minutes, 2,3,4,6 hours and observe each pipe next day and have or not haemolysis and hemagglutination.

Be subjected to reagent thing adding method to see Table 13, the haemolysis determination methods sees Table 14.

Table 13 is subjected to reagent thing adding method

Reagent name	The test tube numbering
	The test tube numbering							1	2	3	4	5	6	7
	Be subjected to reagent thing (ml) sodium chloride injection (ml) distilled water (ml) 2% red cell suspension (ml)	0.1 2.4 - 2.5	0.2 2.3 - 2.5	0.3 2.2 - 2.5	0.4 2.1 - 2.5	0.5 2.0 - 2.5	- 2.5 - 2.5	1	2	3	4	5	6	7	- - 2.5 2.5

Table 14 haemolysis determination methods

Judge index	Judge conclusion
Judge index	Judge conclusion	Full haemolysis part haemolysis does not have the haemolysis coagulation	Solution is transparent redness, and the pipe end is acellular residual.Solution is transparent redness, and the pipe end has a small amount of erythrocyte residual.Erythrocyte all sinks, the supernatant liquid achromatism and clarity.Though red cell agglutination does not appear in haemolysis, can not disperse after the jolting.

12.3. result

See Table 15.

Table 15 lyophilized powder hemolytic test result

Observing time	The test tube numbering
	The test tube numbering							1	2	3	4	5	6	7

15min 30min 60min 2h 3h 4h 6h 24h

- - - - - - - -

+ + + + + + + +

Annotate: "+" expression haemolysis, "-" represents not haemolysis

The result shows: in observing time, supernatant is clear and bright colourless for compound recipe cattle sulphur injection group (1～No. 5 pipe) and sodium chloride injection matched group (No. 6 pipes), and erythrocyte sinks, and does not see haemolysis, erythrocyte energy homodisperse after the jolting, no coagulation; After distilled water matched group (No. 7 pipe) adds erythrocyte, can see haemolysis, the pipe end, is acellular residual, and loseing after the jolting has float in the liquid, and erythrocyte is distilled water and all destroys, and is always red.

12.4. conclusion

Compound recipe cattle sulphur injection is negative to Beagle dog venous blood hemolytic test result.

The specific embodiment

Embodiment 1: the preparation of the injection of pharmaceutical composition of the present invention:

Get taurine 25g, baicalin 10g, puerarin 5g adds water to 1000ml, adjusts pH to 6.5-7.5 with the 1mol/l sodium hydroxide solution, filter, filtrate be potted in 2,5 or the ampoule of 10ml in, 100 ℃ of sterilization 30min obtain injection.

Embodiment 2: the preparation of the injection of pharmaceutical composition of the present invention:

Get taurine 40g, baicalin 30g, puerarin 20g adds water to 1000ml, adjusts pH to 6.5-7.5 with the 1mol/l sodium hydroxide solution, filter, filtrate be potted in 2,5 or the ampoule of 10ml in, 100 ℃ of sterilization 30min obtain injection.

Embodiment 3: the preparation of the powder pin of pharmaceutical composition of the present invention:

Get taurine 25g, baicalin 10g, puerarin 5g adds water to 500ml, adjusts pH to 6.5-7.5 with the 1mol/l sodium hydroxide solution, filter, 100 ℃ of sterilizations of filtrate 30min,,, being potted in the powder pin ampoule of 10ml, 100 ℃ of sterilization 30min obtain the powder pin.

Embodiment 4: the preparation of the mixture of pharmaceutical composition of the present invention:

Get taurine 50g, baicalin 20g, puerarin 10g adds water to 200ml, adjusts pH to 6.5-7.5 with the 1mol/l sodium hydroxide solution, filters, and adds correctivess such as sucrose, is potted in the oral liquid bottle of 10ml, promptly gets mixture.

Embodiment 5: the preparation of pharmaceutical composition tablet of the present invention:

Get taurine 50g, baicalin 20g, puerarin 10g adds starch, carboxymethyl cellulose, granulates tabletting.

Embodiment 6: the system of medicament composition capsule agent of the present invention each:

Get taurine 50g, baicalin 50g, puerarin 30g adds starch, carboxymethyl cellulose, granulates, and the fill capsule promptly gets capsule.

Embodiment 7: the preparation of medicinal composition soft capsule agent of the present invention:

Get taurine 50g, baicalin 50g, puerarin 50g adds vegetable oil, and the fill soft capsule promptly gets soft capsule.

Embodiment 8: the preparation of the pill of pharmaceutical composition of the present invention:

Get taurine 50g, baicalin 20g, puerarin 10g adds starch, refined honey, and general ball promptly gets pill.

Embodiment 9: the preparation of the drop pill of pharmaceutical composition of the present invention:

Get taurine 5g, baicalin 5g, puerarin 5g adds Polyethylene Glycol, and the system drop pill promptly gets drop pill.

Embodiment 10: the preparation of the granule of pharmaceutical composition of the present invention:

Get taurine 50g, baicalin 40g, puerarin 40g adds starch, carboxymethyl cellulose, granulates, and promptly gets granule.

Embodiment 11: the oral liquid of pharmaceutical composition of the present invention is used for the treatment of infantile hyperpyrexia caused by exogenous pathogenic factor:

Get taurine 10g, baicalin 5g, puerarin 2g adds water to 1000ml, adjusts pH to 6.5-7.5 with the 1mol/l sodium hydroxide solution, filters, and adds correctivess such as sucrose, is potted in the oral liquid bottle of 10ml, makes oral liquid.Be used for infantile hyperpyrexia caused by exogenous pathogenic factor's 20 examples, three times on the one, a 10ml, it is obvious to separate thermal effect after taking medicine, the effect that in two hours, all has body temperature to descend, effective percentage is 90%.

Embodiment 12: the oral liquid of pharmaceutical composition of the present invention is used for the treatment of alcoholic liver injury:

Get taurine 40g, baicalin 30g, puerarin 20g adds water to 1000ml, adjusts pH to 6.5-7.5 with the 1mol/l sodium hydroxide solution, filters, and adds correctivess such as sucrose, is potted in the oral liquid bottle of 10ml, makes oral liquid.Be used for the treatment of alcoholic liver injury 40 examples, three times on the one, a 10ml, the back effective percentage of taking medicine is 87.5%.

Embodiment 13: the oral liquid of pharmaceutical composition of the present invention is used for the treatment of chronic hepatitis B:

Get taurine 25g, baicalin 10g, puerarin 5g adds water to 1000ml, adjusts pH to 6.5-7.5 with the 1mol/l sodium hydroxide solution, filters, and adds correctivess such as sucrose, is potted in the oral liquid bottle of 10ml, makes oral liquid.Be used for the treatment of chronic hepatitis B 10 examples, three times on the one, a 10ml, the back feeling of fatigue of taking medicine disappears, and appetite increases, and effective percentage is 100%.

Embodiment 14: the oral liquid of pharmaceutical composition of the present invention is used for the treatment of infantile hyperpyrexia caused by exogenous pathogenic factor:

Get taurine 25g, baicalin 10g, puerarin 5g adds water to 1000ml, adjusts pH to 6.5-7.5 with the 1mol/l sodium hydroxide solution, filters, and adds correctivess such as sucrose, is potted in the oral liquid bottle of 10ml, makes oral liquid.Share with YINQIAO JIEDU KELI, be used for the treatment of infantile hyperpyrexia caused by exogenous pathogenic factor's 10 examples, three times on the one, a 10ml, it is obvious to separate thermal effect after taking medicine, the effect that in two hours, all has body temperature to descend, effective percentage is 90%.

Embodiment 15: the oral liquid of pharmaceutical composition of the present invention is used for the treatment of infantile hyperpyrexia caused by exogenous pathogenic factor:

Claims

1, a kind of Chinese medicine ingredients compositions that is used for the treatment of exogenous high fever and acute and chronic liver injury, it is characterized in that: it is made up of following traditional Chinese medicine components by weight: taurine 1～50 weight portion, baicalin 1～50 weight portion, puerarin 1～50 weight portion.

2, the Chinese medicine ingredients compositions that is used for the treatment of exogenous high fever and acute and chronic liver injury according to claim 1; it is characterized in that: it is made up of following traditional Chinese medicine components by weight: taurine 10～40 weight portions; baicalin 5～30 weight portions, puerarin 2～20 weight portions.

3, the Chinese medicine ingredients compositions that is used for the treatment of exogenous high fever and acute and chronic liver injury according to claim 2, it is characterized in that: it is made up of following traditional Chinese medicine components by weight: taurine 25 weight portions, baicalin 10 weight portions, puerarin 5 weight portions.

4, as claim 1,2 or 3 described pharmaceutical compositions, it is characterized in that: can add other one or more Chinese crude drugs, Chinese medicine extract or middle pharmaceutically active ingredient or Western medicine in this pharmaceutical composition and carry out compatibility, make various medicines.

5, according to claim 1, the 2 or 3 described Chinese medicine ingredients compositionss that are used for the treatment of exogenous high fever and acute and chronic liver injury, it is characterized in that: it can add adjuvant or excipient is made clinical acceptable injection, powder pin, transfusion, mixture, tablet, capsule, soft capsule, pill, drop pill, granule.

6, a kind of described Chinese medicine ingredients method for compositions that is used for the treatment of exogenous high fever and acute and chronic liver injury of claim 1 for preparing is characterized in that: above three flavors, mix, and add right amount of auxiliary materials, mixing is made acceptable clinically various dosage forms.

7, the Chinese medicine ingredients preparation of compositions method that is used for the treatment of exogenous high fever and acute and chronic liver injury according to claim 5, it is characterized in that: get above three flavors, be dissolved in water, adjust pH value to 6.0-8.0 with sodium hydroxide solution, filter, filtrate is potted in the ampoule, and sterilization obtains injection.

8, the Chinese medicine ingredients preparation of compositions method that is used for the treatment of exogenous high fever and acute and chronic liver injury according to claim 5, it is characterized in that: get above three flavors, be dissolved in water, adjust pH value to 6.0-8.0 with sodium hydroxide solution, filter, be potted in the powdery ampoule after the filtrate sterilization, sterilization obtains the powder pin once more.

9, the Chinese medicine ingredients preparation of compositions method that is used for the treatment of exogenous high fever and acute and chronic liver injury according to claim 5, it is characterized in that: get above three flavors, be dissolved in water, adjust pH value to 6.0-8.0 with sodium hydroxide solution, filter, add correctives, be potted in the oral liquid bottle, obtain mixture.

10, the Chinese medicine ingredients preparation of compositions method that is used for the treatment of exogenous high fever and acute and chronic liver injury according to claim 5 is characterized in that: get above three flavors, add starch, carboxymethyl cellulose, granulate, tabletting, obtain tablet or, the fill capsule, obtain capsule or soft capsule or, add starch, refined honey, general ball, obtain pill or, add Polyethylene Glycol, obtain drop pill or, add starch, carboxymethyl cellulose, granulate, obtain granule.