CN103028001A

CN103028001A - Traditional Chinese medicine prescription for relieving asthma, relieving cough and resisting inflammatory, preparation method and application thereof

Info

Publication number: CN103028001A
Application number: CN2011103039264A
Authority: CN
Inventors: 刘建勋; 王书臣; 张鹏; 孟硕; 葛争艳; 金龙; 高凤辉; 张金妹; 何夏秋; 贺建华
Original assignee: Xiyuan Hospital China Academy Of Chinese Medical Sciences
Current assignee: GUIZHOU JIANXING PHARMACEUTICAL CO Ltd
Priority date: 2011-09-29
Filing date: 2011-09-29
Publication date: 2013-04-10
Anticipated expiration: 2031-09-29
Also published as: CN103028001B

Abstract

The invention relates to a traditional Chinese medicine extract prepared by traditional Chinese medicine raw materials consisting of ephedra, scutellaria baicalensis, liquorice and vitex oil, a traditional Chinese medicine mixture comprising liquiritin, ephedra total alkali, baicalin and vitex oil as active components, a traditional Chinese medicine composition containing the traditional Chinese medicine extract or the traditional Chinese medicine mixture, and application in clinic thereof. The prescription disclosed by the invention has anti-inflammatory, antipyretic, spasmolysis, anti-asthmatic, anti-cough, eliminating phlegm, immuno-enhancement, antibacterial or antiviral effects and can be used for treating and/or preventing the respiratory system inflammation such as bronchitis, trachitis, pneumonia and the like.

Description

A kind of be used to relieving asthma, antitussive, the Chinese prescription of antiinflammatory, Its Preparation Method And Use

Technical field

The present invention relates to a kind of Chinese medicine extract of being made by the raw material of Chinese medicine that comprises Herba Ephedrae, Radix Scutellariae, Radix Glycyrrhizae and Oleum Viticis Negundo, comprise liquirtin, Herba Ephedrae total alkali, baicalin and Oleum Viticis Negundo as the Traditional Chinese drug mixture of active component and the Chinese medicine composition that comprises described Chinese medicine extract or Traditional Chinese drug mixture, and they are in clinical application.Chinese medicine extract of the present invention, Traditional Chinese drug mixture and Chinese medicine composition have antiinflammatory, analgesic, spasmolytic, relieving asthma, antitussive, eliminate the phlegm, strengthen the effects such as immunity, antibiotic or antiviral, can be used for treating and/or preventing inflammation in respiratory system, such as bronchitis, tracheitis, pneumonia etc.

Background technology

Inflammation in respiratory system is trachea, bronchus and the pneumonia that is caused by factors such as antibacterial, virus and physics or chemical stimulations.Morbidity season is common with the Winter-Spring, and sickness rate was directly proportional with the age, especially take the northern China rural area as multiple.

Inflammation in respiratory system is divided into acute and chronic two kinds according to the length of the course of disease, and wherein chronic bronchitis is more common in middle-aged and elderly people, so the title of " old-slow-bronchial tube " is arranged again.High, the Relapse rate of chronic bronchitis sickness rate can concurrent obstructive emphysema, even pulmonary hypertension, pulmonary heart disease, has a strong impact on patient's live and work.

If inflammation in respiratory system repeated infection Chang Yi causes obstructive emphysema, small number of patients can concurrent bronchiectasis.Inflammation in respiratory system belongs to the categories such as Chinese medicine " cough ", " phlegm retention ", " cough with asthma ".Thinking exopathogen invasion and attack and lung, spleen, kidney three dirty malfunctions, is the main cause that causes primary disease.The human righteousness is not enough, defends outer dereliction of duty, and being invaded by exogenous pathogen, exopathogen both can be the heresies of wind and cold, the also heresy of wind heat, but lungs are invaded in the also evil heat-transformation of wind and cold, make impaired depurative descending of lung QI; Or insufficiency of lung-QI, weakened defensive QI is felt exopathogen again; Or weak with age, deficiency of both the splenic and pulmonary QI, dysfunction of the spleen in transportation wets and gathers into expectorant, stops holding in lung; Or lung has chronic disease, feels again exopathogen; Or after the prolonged illness, undermine kidney by the spleen lung, and causing deficiency of kidney-QI, improving inspiration by invigorating kidney-QI is had no right etc.

Chinese medicine is of a great variety, different compatibilities, and each is variant for the effect for the treatment of chronic bronchitis, such as danggui liuhuang decoction scalable body equilibrium between yin and yang, improves and enhancing human body immunity power, improves treatment rate, and has no adverse reaction; Linggui zhugan decoction cures mainly under the heart phlegm retention, and distention and fullness in the chest and hypochondrium is established for phlegm retention is sick; Cortex mori decoction plus-minus has the merit that removing heat-phlegm, respectful lung are relievingd asthma; Belamcanda mahuangtang cures mainly cough with asthma and can not put down sleepingly, rings between larynx such as water bird sound, and thin white phlegm, thirsty drink, tongue is white, stringy and tense pulse etc.; Suzi Jiangqi Tang makes gas fall expectorant to disappear the self-balancing of then breathing with cough; Xuanbaichengqitang lung qi dispersing purging FU-organs, internal organs are ruled together, and it is normal that ascending or descending movement of vital Qi recovers, and then cough, dyspnea with rapid and short breath, all diseases of constipation are from eliminating; Five tastes Fructus Hippophae is loose to be Mongols's proved recipe, has relieving cough and relieving asthma, the heat clearing away effect of eliminating the phlegm, the clinical chronic pyretic pulmonary cough that is mainly used in, and the dyspnea with rapid and short breath abundant expectoration, fullness in the chest is vexed, and the breast side of body is had a pain.

Summary of the invention

The inventor comes from theory of Chinese medical science, sums up in many ways experience, has made the present invention.

Traditional medicine is thought that lung governing qi belongs to and is defended, and closes fur outward.The exopathogen invasion and attack, pulmonary function is not normal, is the main cause that causes primary disease.The human righteousness is not enough, defends outer dereliction of duty, and being invaded by exogenous pathogen, exopathogen both can be the heresies of wind and cold, the also heresy of wind heat, but lungs are invaded in the also evil heat-transformation of wind and cold, make impaired depurative descending of lung QI; Or insufficiency of lung-QI, weakened defensive QI is felt exopathogen again, and dysfunction of the spleen in transportation wets and gathers into expectorant, stops holding in lung.The heresy of wind and cold is outer attacks the flesh table, makes defensive QI being obstructed, and space between skin and muscles is inaccessible, and a surname who affects lung qi is respectful descending, and then superinverse is for breathing heavily.Control and work as depressed lung-energy dispersing.Side's epheday intermedia toil is warm in nature, returns lung and urinary bladder channel, is apt to open natural fibre line of meat diaphoresis, dispels at the wind and cold of table; Property lightly floats, and ends cough with dyspnea, and depressed lung-energy dispersing opens and closes strongly fragrant lung qi, disperses the lung meridian stagnated fire, so we are with thinking monarch drug.Radix Scutellariae bitter cold, energy eliminating the pathogens from the lung have the merit of promoting the circulation of QI expectorant concurrently through the fire of edema caused by disorder of QI.With the Herba Ephedrae compatibility, be used for expectorant heat stagnation lung, the card of impairment of dispersing and descending function of the lung plays clearly lung qi dispersing gas, the effect of removing heat from the lung and dissipating phlegm.The little hardship of Herba Viticis Cannabifoliae, suffering, flat.Hardship can be fallen, hot can faling apart; Fall then and reduce phlegm, loose then dispel the wind, the disease of wind-phlegm should it.Radix Glycyrrhizae is sweet flat, and slow lung qi is anxious, and in just protect.The merit of while tool expelling phlegm for arresting cough, and can prevent that the Herba Ephedrae diaphoresis is too to hinder healthy energy.All medicines share, and heat clearing away is eliminated the phlegm, relieving cough and relieving asthma.

Therefore, aspect first, the invention provides a kind of Chinese medicine extract, it is made by the raw material that comprises following Chinese medicine: Herba Ephedrae 100-200 weight portion, Radix Scutellariae 100-200 weight portion, Radix Glycyrrhizae 100-200 weight portion, Oleum Viticis Negundo 0.2-1 weight portion.

In a preferred embodiment, Chinese medicine extract of the present invention mainly comprises liquirtin, Herba Ephedrae total alkali, baicalin and Oleum Viticis Negundo isoreactivity composition.

Aspect second, the invention provides a kind of Traditional Chinese drug mixture, it comprises following active component: liquirtin, Herba Ephedrae total alkali, baicalin and Oleum Viticis Negundo, wherein the weight ratio of liquirtin, Herba Ephedrae total alkali, baicalin, Oleum Viticis Negundo is 2～2.5: 1: 2～2.5: 0.02～0.2, and preferred 2.5: 1: 2.5: 0.04.The medical materials such as described liquirtin, Herba Ephedrae total alkali, baicalin and Oleum Viticis Negundo can each free Radix Glycyrrhizaes, Herba Ephedrae, Radix Scutellariae and Herba Viticis Cannabifoliae are prepared from by extracting method of the present invention, also can be commercially available finished products.

Chinese medicine extract of the present invention or Traditional Chinese drug mixture can also be made Chinese medicine composition with one or more medicinal adjuvants, excipient, diluent or solvent according to method well known in the art as effective ingredient.

Aspect the 3rd, the invention provides the preparation method of Chinese medicine extract of the present invention, the method may further comprise the steps:

1) gets the Herba Ephedrae cutting, add 10-16 times of decocting and boil 2-4 time.Each 1-3 hour, filter, filtrate is concentrated into dried, and is for subsequent use;

2) get baikal skullcap root decoction pieces, add 6-10 times of water gaging, decoct 2-4 time, each 1-2 hour, collecting decoction was concentrated into 1/3 decocting liquid volume, regulate pH value to 4.0, leave standstill and remove sticking paste impurity after 1 hour, get supernatant, regulate pH value to 2.0, left standstill abandoning supernatant 12-24 hour at 4 ℃, precipitation adds the water stirring makes its suspendible, filter out impurities, be deposited in 80 ℃ of lower drying under reduced pressure, for subsequent use;

3) the extracting liquorice medical material adds 10-16 times of water gaging and decocts 2-4 time, and each 2-3 hour, collecting decoction filtered, and filtrate is concentrated into 1/2 volume, and adjust pH to 2.0 only leaves standstill when treating to separate out without yellow mercury oxide, and abandoning supernatant is deposited in 60 ℃ of lower drying under reduced pressure, and is for subsequent use;

4) according to Oleum Viticis Negundo: beta-schardinger dextrin-: water is 1: 6～10: 50～100 weight ratio, get the beta-schardinger dextrin-of respective amount, be added to the water, heating makes it to dissolve fully, puts to be cooled under the room temperature below 50 ℃, and stir on the limit, the limit adds Herba Viticis Cannabifoliae volatile oil, and under constant temperature, continue to stir 1-3 hour, to put 4 ℃ and left standstill 8-12 hour, the sucking filtration precipitate is to doing;

5) with step 1)～step 4) in the product that obtains mix and get final product.

In above-mentioned preparation method, the medical material amount of use is respectively: Herba Ephedrae 100-200 weight portion, Radix Scutellariae 100-200 weight portion, Radix Glycyrrhizae 100-200 weight portion, Oleum Viticis Negundo 0.2-1 weight portion.

Aspect the 4th, the invention provides Chinese medicine extract of the present invention, Traditional Chinese drug mixture or comprise the purposes of the Chinese medicine composition of this Chinese medicine extract or this Traditional Chinese drug mixture, described Chinese medicine extract, Traditional Chinese drug mixture and Chinese medicine composition have antiinflammatory, analgesic, spasmolytic, relieving asthma, antitussive, eliminate the phlegm, strengthen at least a effect in immunity, the antibiotic or antiviral.Described Chinese medicine extract and Chinese medicine composition can be used for treating and/or preventing inflammation in respiratory system, such as bronchitis, tracheitis, pneumonia etc.

Aspect the 5th, the purposes of the Chinese medicine composition that the invention provides Chinese medicine extract of the present invention, Traditional Chinese drug mixture or comprise this Chinese medicine extract or this Traditional Chinese drug mixture in the preparation medicine, described medicine are used for the treatment of and/or prevent at least a in the following clinical symptoms: cough, heating, dyspnea, spitting of blood, expectoration, out of breath, wheezing, pant, chest pain etc.

Aspect the 6th, the purposes of the Chinese medicine composition that the invention provides Chinese medicine extract of the present invention, Traditional Chinese drug mixture or comprise this Chinese medicine extract or this Traditional Chinese drug mixture in the preparation medicine, described medicine is used for the treatment of and/or prevents at least a in the following clinical sign: hyperpyrexia, and sweating and not understanding, it is out of breath to cough, flaring of nares is rough, the Huang of coughing up phlegm is thick or cough up rusty expectoration, chest pain, and thirsty agitation; yellowish or reddish urine is hard and dry.Red tongue with yellow fur, slippery and rapid pulse or big vast number.

The present invention obtains state natural sciences fund (81073060) and subsidizes.

The specific embodiment

The Chinese medicinal material general introduction

The Herba Ephedrae of mentioning among the present invention (Herbal Ephedrae) is Ephedraceae plant plait Herba Ephedrae (Ephedra sinica), the herb stem of epheday intermedia (Ephedra intermedia) or ephedra equisetina (Ephedra equisetina), it is a kind of wind-cold-dispersing medicinal, its main active chemical comprises that organic amine alkaloids (comprises L-ephedrine (L-ephedrine), d-pseudo-ephedrine (d-pseudoephedrine), L-N-methylephedrine etc.; Oxazolone Alkaloid: Herba Ephedrae oxazolone (ephedroxane); Volatile oil: α, α, 4-trimethyl-3 cyclohexene-methanol (α, α-4-trimethyl-3-cyclohexen-1-methanol), β-terpineol (β-terpineol) etc.; Flavone compound: apigenin (apigenin), tricin (tricin), kaempferol (laemplerol), apigenin-5-rhamnose (apigenin-5-rhamnoside) etc.The main pharmacological of Herba Ephedrae comprises: diaphoresis; Relieving asthma; Diuresis; Antiinflammatory, antiallergic; Antitussive, eliminate the phlegm; Analgesic, antibiotic, antiviral etc.Above-mentioned three kinds of Herba Ephedraes all can be used as the medical material use in the present invention, and can directly use in the present invention the Herba Ephedrae total alkali that therefrom extracts.

The Radix Scutellariae of mentioning among the present invention (Radix Scutellariae) is the root of labiate Radix Scutellariae Scutellaria baicalensis Georgi, and its main chemical compositions comprises baicalin (baicalin), baicalin (baicalein), wogonoside (wogonoside), wogonin (wogonin), Radix Scutellariae ketone I, II (skullcapflavone I, II), oroxylin A (oroxy-linA) and campesterol.The main effect heat clearing and damp drying of Radix Scutellariae, eliminating fire and detoxication, cooling blood for hemostasis, heat extraction is antiabortive. and Radix Scutellariae mainly contains baicalin, baicalin, wogonin, and the compositions such as wogonoside, neobaicalein, cupreol can directly use the baicalin that therefrom extracts in the present invention.Its antimicrobial spectrum is wider, and various bacteria, dermatophytes, leptospira etc. are had inhibitory action.Even to the staphylococcus aureus that the antibiotic such as penicillin develop immunity to drugs, still very sensitive to Radix Scutellariae.The effects such as Radix Scutellariae also has blood pressure lowering, calmness, diuresis, protects the liver, function of gallbladder promoting, antiallergic, releasing smooth muscle spasm have synergism with ephedrine.

The Radix Glycyrrhizae of mentioning among the present invention is the root and rhizome of glycyrrhizic legume Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. G.inflata Bat. or Glycyrrhiza glabra L. G.glabra L..Main chemical compositions comprises triterpenes (potassium of triterpene saponin glycyrrhizic acid, calcium salt are glycyrrhizin, are the sweet ingredients of Radix Glycyrrhizae), flavonoid, alkaloid, polysaccharide etc., can directly use in the present invention the liquirtin that therefrom extracts.Radix Glycyrrhizae has anti-arrhythmia effect; Antiulcer is arranged, and gastric acid secretion inhibiting is alleviated gastrointestinal smooth muscular spasm and analgesic activity, and with the effective ingredient peoniflorin of Radix Paeoniae synergism is arranged; Can promote pancreatic secretion; Obvious antitussive effect is arranged, and phlegm-dispelling functions is also more remarkable, also has certain antiasthmatic effect; Antibiotic, antiviral, antiinflammatory, anti-allergic effects are arranged; Can protect throat and the tunica mucosa tracheae of inflammation; Some poisonous substance there is the Detoxication of similar glucuronic acid; The effect of similar adrenocortical hormone sample is arranged; The effect such as also have diuresis, blood fat reducing, protect the liver.

The Oleum Viticis Negundo of mentioning among the present invention is the volatile oil that the fresh leaf of Verbenaceae Herba Viticis Cannabifoliae Vitex negundo L.var.cannabifolia (Sieb.et Zucc.) Hand.-Mazz. obtains through steam distillation.Oleum Viticis Negundo has and eliminates the phlegm, cough-relieving, and the effect of relievining asthma is usually used in treating chronic bronchitis.

Pharmaceutical dosage form

Chinese medicine extract of the present invention can further be made suitable pharmaceutical dosage form with pharmaceutical carriers such as one or more adjuvants, excipient, diluent, solvent, stabilizing agent, disintegrating agent, flavoring agent, coloring agent, PH regulator, dispersant, isotonic agent and/or other additives respectively.Comprise in the dosage form process of medicine of the present invention in preparation, Chinese medicine extract of the present invention or Chinese medicine composition usually are prepared by techniques such as the mixing of routine, dissolving, granulation, ingot grinding processed, emulsifying, encapsulation, embedding or lyophilizing with one or more pharmaceutical carriers, effective ingredient of the present invention (Chinese medicine composition or Chinese medicine extract) dilutes or is encapsulated in wherein (sees Remington ' s Pharmaceutical Sciences, the 15 edition, Hoover, J.E. edit Mack Publishing Co. (2003)).

Above-mentioned dosage form can be taked any suitable administering mode, and this mode comprises the part, through approach such as eye, per os, whole body, per nasal, injection, transdermal, rectum, vaginas, or sucks or be blown into the form of administration.

For topical, medicine of the present invention can be made into solution, gel, ointment, emulsifiable paste, suspension etc.

The whole body preparation comprises by drug administration by injection, for example in subcutaneous, intravenous, intramuscular, the sheath or the dosage form of peritoneal injection, and is used for transdermal, the saturating dosage form of mucosa oral cavity or pulmonary administration.

Injectable dosage formulations comprises sterile suspensions, solution or the emulsion of medicine of the present invention in aqueous or oiliness medium.Described dosage form also can contain suspending agent, stabilizing agent and/or dispersant etc.Injection type can provide by unit dosage forms, for example, in ampoule or in the multidose container, can contain antiseptic.

Injectable dosage formulations also can be selected the form of powder, uses before use suitable vehicle, includes but not limited to asepticly again prepare without heat source water, buffer, glucose solution etc.Injectable dosage formulations can be by direct intravenous injection, the administration of vein fast drip, or carries out the infusion administration by adding infusion solution such as 0.9% sodium chloride injection or other compatible infusion solutions.

For oral administration, medicine of the present invention can use pharmaceutical excipient and/or additive to be prepared into for example dosage form of lozenge, tablet or capsule by the mode of routine.The liquid dosage form that is used for oral administration can be taked for example form of elixir, solution, syrup or suspension, maybe can be powder, and water or other suitable vehicle are prepared.This liquid dosage form can be prepared with medical additive by the mode of routine.

Oral Preparation can be formulated into and be the controllable release dosage form, and its preparation technology and method are known in the art.

Pharmaceutical dosage form of the present invention is preferably peroral dosage form or parenteral dosage form.Peroral dosage form comprises tablet, capsule, lozenge, elixir, syrup, suspensoid and powder etc., preferred tablet and capsule formulation.Parenteral dosage form comprises injectable dosage formulations, suppository and spray, preferred injection, lyophilized injectable powder and injection etc.

Drug therapy purposes of the present invention

Chinese medicine extract of the present invention, Traditional Chinese drug mixture or Chinese medicine composition (following abbreviation " medicine of the present invention ") have antiinflammatory, analgesic, spasmolytic, relieving asthma, antitussive, eliminate the phlegm, strengthen at least a effect in immunity, antibacterium or the antiviral, at least a or multiple in the clinical symptoms such as it can be used for treating cough that the various causes of disease cause, heating, dyspnea, spitting of blood, expectoration, out of breath, wheezing, pants, chest pain.

From the angle of the traditional Chinese medical science, the clinical sign that the present invention relates to comprises hyperpyrexia, sweating and not understanding, and it is out of breath to cough, and flaring of nares is rough, and it is yellow thick or cough up rusty expectoration to cough up phlegm, chest pain, thirsty agitation, yellowish or reddish urine is hard and dry.Red tongue with yellow fur, slippery and rapid pulse or big vast number.

Medicine of the present invention can be for the preparation of at least a medicine that treats and/or prevents in the following inflammation: comprise that the biopathogen body comprises the inflammation that antibacterial, fungus, virus, mycoplasma, chlamydia, legionella, rickettsia, Pneumocystis carinii etc. cause, and the inflammation that causes of the abiotic pathogen factor.

In the present invention, antibacterial is selected from least a in the following antibacterial: staphylococcus aureus, staphylococcus epidermidis, streptococcus, escherichia coli, micrococcus catarrhalis, klebsiella spp, legionella, bacillus pyocyaneus, streptococcus pneumoniae and Bacillus proteus.

In the present invention, virus is selected from least a in following: influenza virus (influenza virus (influenza virus), Coxsackie virus, coronavirus (comprising the mutation (SARS virus) that causes the lung typical pneumonia), Measles virus, parainfluenza virus (human parainfluenza virus (HPIVs), respiratory syncytial virus, rhinovirus, adenovirus, herpesvirus, cytomegalovirus.

In a preferred embodiment of the invention, described inflammation is inflammation in respiratory system, comprises the inflammation at the positions such as lung and respiratory tract (nasal cavity, pharynx, larynx, trachea, bronchus) pipe.

According to course of disease classification, the inflammation in respiratory system that the present invention relates to can comprise acute (propping up) tracheitis, chronic (propping up) tracheitis, acute pneumonia, chronic pneumonia etc.

According to etiological classification, the inflammation in respiratory system of mentioning among the present invention can comprise:

1. the inflammation in respiratory system that causes of biopathogen body comprises:

(1) inflammation that causes such as bacterial inflammation such as streptococcus pneumoniae, staphylococcus aureus, α-hemolytic streptococcus, bacillus canalis capsulatus, hemophilus influenza, Pseudomonas aeruginosa.

(2) inflammation that causes of the inflammation due to the atypia pathogen such as legionella, mycoplasma and chlamydia etc.

(3) inflammation that causes such as viral inflammation such as coronavirus, adenovirus, influenza virus.

(4) inflammation that causes such as fungoid inflammation such as Candida albicans, aspergillosis, actinomyces.

(5) inflammation that causes such as the inflammation due to other pathogen such as rickettsia, toxoplasma, protozoon;

2. the inflammation in respiratory system that causes of the abiotic pathogen factor.Comprise

(1) chemical inflammation of causing such as the inflammation due to the chemical factors such as radioactive inflammation, gastric acid suction, medicine etc.Described chemical factors comprises 1) chemical substance, comprise endogenous and xenobiotics.Xenobiotics such as strong acid, highly basic and Oleum Terebinthinae, mustard gas etc.; The endogenous chemical substance comprises the catabolite of toxicant such as slough and is piled up in metabolite in the body such as carbamide etc. under some pathological conditions; 2) physical agent comprises high temperature, low temperature, radioactive substance and ultraviolet etc. and mechanical damage etc.; 3) foreign body namely enters the foreign body of human body by all means, such as various metals, wood chips, dust granules, and sutures etc., because its antigenicity is different, can cause inflammatory reaction in various degree.

(2) slough: the reasons such as ischemia or anoxia can cause tissue necrosis, and tissue necrosis is potential pro-inflammatory cytokine, and the congested hemorrhage band that occurs at fresh infarct edge and the infiltration of inflammatory cell all are the performances of inflammation.

(3) allergy: namely when the organism immune response abnormal state, can cause inappropriate or excessive immunoreation, cause tissue and cell injury and cause inflammation.The tissue injury that immunoreation causes is most commonly in various types of allergy: I allergic reaction type such as allergic rhinitis, urticaria, II allergic reaction type such as anti-substrate membranous glomerulonephritis, glomerulonephritis due to III allergic reaction type such as the immune complex deposit, IV allergic reaction type such as tuberculosis, typhoid fever etc.; In addition, also have many autoimmune diseasees such as lymphocytic thyroiditis, ulcerative colitis.

Clinical symptoms and sign

The part clinical symptoms and the clinical sign that relate among brief description the present invention:

Cough: the zest dry cough of acute attack occur together heat, hoarseness person are common in acute laryngitis, tracheitis, bronchitis; All the year round cough, increase the weight of autumn and winter, considers chronic bronchitis more; Cough during Body Position Change, expectoration aggravation, common in bronchiectasis or pulmonary abscess; Cough companion chest pain is more common in pneumonia, pleuritis; Ictal dry cough (especially in rule outbreak at night), the prompting cough variant asthma; Loud and sonorous dry cough may be that lung bronchogenic carcinoma is involved trachea or main bronchus with dyspnea; The irritable cough that continues and increase the weight of is gradually then considered idiopathic pulmonary interstitial fibrosis or bronchovesicular cancer with tachypnea.

Expectoration: the character of expectorant, amount and abnormal smells from the patient have certain help to diagnosis.General expectorant transfers purulence to by white foam or mucus shape and mostly is bacterial infection; A large amount of yellowish purulent sputums are common in pulmonary abscess or bronchiectasis; Rust sample expectorant may be streptococcus pneumoniae infection; Rufous gel-shaped expectorant often points out bacillus canalis capsulatus to infect; During companion's anaerobic infection, purulent sputum foul smelling flavor; During pulmonary edema, cough pink thin frothy sputum; Pulmonary amebiasis is coffee sample expectorant; Paragonimiasis westermani is jam expectorant.The increase and decrease of amount of expectoration, the aggravation that reflection is infected or the alleviation of inflammation.

Spitting of blood: apoplexy due to phlegm is pulmonary tuberculosis with blood often. the common sympton of pulmonary carcinoma.Cough up blood (particularly 24 hours more than 300 milliliters), be more common in bronchiectasis. also be found in pulmonary tuberculosis; The pulmonary venous pleonaemia that acute bronchitis, pneumonia, pulmonary infarction, mitral stenosis cause also can be spat blood, but all is short-term.

Dyspnea: dyspnea is mainly manifested in the aspects such as respiratory frequency, the degree of depth and the rhythm and pace of moving things.Be divided into acute, chronic and repeated relapsing by its outbreak speed.Acute tachypnea companion chest pain is often pointed out pneumonia, pneumothorax, hydrothorax; The chronic progressive external tachypnea sees chronic obstructive pulmonary disease, diffuse interstitial pulmonary fibrosis; During bronchial asthma attack, expiratory dyspnea often appears, and companion's wheezing sound, but complete obiteration during alleviation, and symptom occurs again during the next time outbreak.Dyspnea is divided into three kinds of air-breathing property, expiration and Combination.Laryngeal edema, laryngotracheitis disease, tumor or foreign body cause when upper respiratory tract is narrow, the inspiratory stridor sound occurs; Asthma or asthmatic bronchitis cause the extensive bronchospasm of lower respiratory tract, then cause the expiration wheezing sound.With cationic chitin, in intestinal, be combined with fat and bile acid, fat digestion capable of blocking and absorption, clear function of gallbladder promoting road reduces neutral fat and low density lipoprotein, LDL, and thrombus prevents arteriosclerosis and apoplexy.

Chest pain: lung and visceral pleura are insensitive to the pain sensation, when the pathological changes such as pneumonia, pulmonary tuberculosis, pulmonary infarction, pulmonary abscess are involved parietal pleura, chest pain can occur.The high heat of chest pain companion should be considered pneumonia.When cancer is invaded and when parietal pleura or rib, dull pain occurred, continue aggravation, so cutting pains; Pleuritis often causes chest pain under the larger both sides of thorax activity, with cough, dark air-breathing relevant; Severe pain can occur suddenly in spontaneous pneumothorax when play is coughed or held one's breath.

Tcm clinical practice sign: from the angle of the traditional Chinese medical science, pathogenic factor in the exterior is not understood and in entering, the strongly fragrant lung of pathogenic heat, lung are defended closing, and sees hyperpyrexia, no relieving of symptom after perspiration; Pathogenic heat are stopped up the resistance lung qi, impairment of purifying function of the lung, so it is out of breath to cough, flaring of nares is rough, expectorant Huang or rust; Injury of blood vessel of the lung by heat is chest pain then; Consumption of body fluid by heat and see thirstyly, yellowish or reddish urine is hard and dry; And red tongue with yellow fur, slippery and rapid pulse or big vast number average are levying of accumulatiorn of pathogenic heat in the lung.

The disease general introduction

Bacterial inflammation: bacterial pneumonia (bacterialpneumonia) accounts for 80% of all kinds of pathogen pneumonia of adult.Entered antibiotic since the epoch, the prognosis of bacterial pneumonia once significantly improves, but case fatality rate occupies height and do not fall after the sixties.By the anatomy classification, pneumonia can be divided into Da Ye, lobule and a matter.Press etiological classification, mainly contain infectious and physics and chemistry such as lonizing radiation, poison, medicine and allergy such as hypersensitivity pneumonitis etc., clinical findings is most to be the infectious pneumonia that antibacterial, virus, chlamydia, mycoplasma, rickettsia, fungus and parasite etc. cause, wherein common with antibacterial.

The pathogen of pneumonia has larger difference because of host's age, accompanying diseases and immune functional state, acquisition pattern (community acquired pneumonia or nosocomial pneumonia in patients).The commonly encountered diseases substance of community acquired pneumonia is streptococcus pneumoniae, hemophilus influenza, staphylococcus aureus, micrococcus scarlatinae, legionella, anaerobe and virus, mycoplasma and chlamydia etc., and is then common with bacillus pyocyaneus and other pseudomonass, pneumobacillus, escherichia coli, Bacillus proteus, Methicillin-resistant Staphylococcus aureus (mrsa) and fungus etc. in the nosocomial pneumonia in patients.The aspiration pneumonitis great majority are anaerobic infection.

Inducement or the underlying diseases such as companion's chronic obstructive pulmonary disease, heart failure such as bacterial pneumonia patient Chang You catches cold, fatigue have the upper respiratory tract infection history before 1/3rd diseases.Most onsets are more anxious.Part gram negative bacillus pneumonia, senile pneumonia, the concealment of nosocomial pneumonia in patients onset.It is common to generate heat, and mostly is to continue high heat, and pattern of fever can not be true to type behind the antibiotic therapy.Cough, expectoration.The staphylococcus aureus of microscopically is a lot of, is dry cough in early days, and expectoration is gradually arranged, and how many amounts of expectoration differs.Sputum is purulence more, and the more typical expectorant of golden Portugal's bacterium pneumonia is yellow pus; Pneumococcal pneumonia is rusty expectoration; Klebsiellar pneumonia is the brick-red sticking sample that freezes; Pyocyanic pneumonia is light green; Anaerobic infection is often accompanied stink.It is rare to be developed to above-mentioned typical sputum performance behind the antibacterial therapy.Spitting of blood is rare.Part has chest pain, then is prickling-like pain when involving pleura.The inferior lobe pneumonia stimulates diaphragmatic pleura, and pain can be radiated to shoulder or abdominal part, and the easy mistaken diagnosis of the latter is acute abdomen.General Symptoms has headache, muscular soreness, weak, the gastrointestinal symptoms such as feeling sick appears in minority, vomiting, abdominal distention, diarrhoea.The neurological symptoms such as that the patient with severe symptoms can have is drowsiness, disturbance of consciousness, convulsions.

Viral inflammation: viral pneumonia (viral pneumonia) is by upper respiratory tract infection, the pneumonia due to spreading downwards.Can occur in immunologic function is normal or suppress child and adult.Primary disease betides winter-spring season mostly, can break out or distribute popular.Viral pneumonia is apsiration infection, by person to person's droplet infection, mainly be spread downwards by upper respiratory tract infection due to, often accompany tracheitis and bronchitis.In acute respiratory infection, viral infection accounts for 90%, and common cold, pharyngitis, larynx-tracheitis and bronchitis, bronchiolitis, baby's herpangina (herpangina) and epidemic pleurodynia (pleurodynia) etc. are arranged.Cause that the virus of pneumonia is take influenza virus as common, other are parainfluenza virus, cytomegalovirus, adenovirus, rhinovirus, coronavirus and some enterovirus, such as COxsackie, echovirus etc., and the virus such as herpes simplex, varicella-zoster, rubella, measles.Infant also often produces pneumonia by respiratory syncytial virus infection.The patient can be subjected to more than one viral infection simultaneously, and the infection of Chang Jifa antibacterial, and immunosuppressed host is Chang Jifa fungus and protozoan infection also.

The fungoid inflammation: the fungus that causes inflammation in respiratory system is aspergillosis, Nocardia, cryptococcus, Histoplasma capsulatum for example; Candidiasis, it is the bacterial parasite of oral cavity, skin, intestinal and vagina; Actinomycetes, it is the dental decayed tooth bacterial parasite.Other position fungal infection also can follow lymph or blood to pulmonary in the body, actinomycetes in the focus under cervical region, the diaphragm for example, and this type of is the Secondary cases Pulmonary Fungal Infections.Fungal pneumonia often is secondary to infantile pneumonia, pulmonary tuberculosis, diabetes, hematopathy etc.; Using antibiotics and hormone etc. is main inducing, and this is because penicillin has the effect that stimulates the Candida albicans excessive multiplication; Broad ectrum antibiotic suppresses Endophytic bacteria, makes candidiasis lose the restriction of antibacterial; 17-hydroxy-11-dehydrocorticosterone can suppress the immunologic function in the body.It has bronchopneumonic various sings and symptoms, but onset is slow, and how pneumonia occurs or aggravation in using antibiotic therapy, and heating can be arranged, and cough is violent, and expectorant is colourless gel-shaped, the idol band blood streak.Auscultation of lung can have middle fine bubbling rale.

Alterative inflammation: hypersensitivity pneumonitis (hypersensitivitypneumonitis) is one group of non-asthma allergic pulmonary disease that is caused by different sensitinogens, and is scorching in its pathological characters take diffuse interstitial.Therefore system is called again extrinsic allergic alveolitis (extrinsicallergicalveolitis) owing to suck the caused anaphylaxis of Organic substance dirt particle (diameter＜10 μ) that contains fungal spore, bacterial product, animal protein or insecticide antigen.Allergen is the Organic substance dust granules that contains fungal spore, bacterial product, animal protein or insecticide antigen.Acute person, originally the patient of sensitization can have heating, fear of cold, and cough and dyspnea generally come across and again contact behind the antigen 4～8 hours.Also anorexia, nausea and vomiting can appear.Auscultation of lung has detail inspiratory phase moist rales, and wheezing sound is uncommon.Break away from after the antigen, symptom was generally improved in several hours, but need to recover fully several weeks, and outbreak can cause pulmonary fibrosis repeatedly.Subacute person can hiddenly attack morbidity, and cough and dyspnea continue a few days to several weeks, and state of an illness development person needs hospitalization.Chronic person, carry out dyspnea after the sexual activity, cough, weak and weight loss can reach the several months to the several years.Disease can develop into respiratory failure.

The present invention will be further described by the following examples.Embodiment only is used for illustrating implementation method of the present invention and effect, does not limit in any form the present invention.Mentioned Chinese medicine, raw material, excipient, diluent, adjuvant, reagent or other drugs etc. among the following embodiment except as otherwise noted, all are commercially available prod.As do not specify, " % " of the material of then wherein mentioning is % by weight, " part " is weight portion.

[Preparation Example]

Preparation Example 1

Proportioning raw materials:

More than four flavors, the Herba Ephedrae cutting adds 12 times of decoctings and boils secondary, each 1.5 hours, filter, filtrate is concentrated into dried, and is for subsequent use.Baikal skullcap root decoction pieces adds 8 times of water gagings, decocts three times, and each 1 hour, collecting decoction was concentrated into 1/3 decocting liquid volume, adds the 2mol/L hydrochloric acid solution and regulates pH value to 4.0, leaves standstill 1 hour, removes the impurity of sticking paste; Get supernatant, add again the 2mol/L hydrochloric acid solution and regulate pH value to 2.0,80 ℃ of lower insulations 30 minutes, put 4 ℃ and left standstill 12 hours.Abandoning supernatant, precipitation add the water stirring makes suspendible, and double gauze filters out impurities, and filtrate is after precipitating, and water re-using is washed till pH value more than 5.0 again, filters, and is deposited in 80 ℃ of lower drying under reduced pressure, and is for subsequent use.Radix Glycyrrhizae adds 12 times of water gagings and decocts secondary, each 2 hours, collecting decoction filtered, filtrate is concentrated into 1/2 volume, add concentrated sulphuric acid adjust pH to 2.0, leave standstill when treating to separate out without yellow mercury oxide and end, put 5 ℃ of cold preservations and spend the night, abandoning supernatant, precipitation blunge wash to pH value closely neutral, 60 ℃ of lower drying under reduced pressure, for subsequent use.Oleum Viticis Negundo is according to oil: beta-schardinger dextrin-: water is 1: 8: 70 ratio, gets the beta-schardinger dextrin-of respective amount, is added to the water, heating makes it to dissolve fully, puts to be cooled under the room temperature below 50 ℃, and stir on the limit, the limit adds the volatile oil of prescription ratio, and continues to stir 1.5 hours under constant temperature.Put 4 ℃ and left standstill 8 hours, the sucking filtration precipitate is to doing.Merge the said extracted thing, add adjuvant, granulation incapsulates, and get final product.

Preparation Example 2

Proportioning raw materials: adopt the extraction dry powder of following Chinese medicine, in following ratio weighing:

Liquirtin, 275mg

The Herba Ephedrae total alkali, 110mg

Baicalin, 275mg

Oleum Viticis Negundo, 40mg

Betacyclodextrin, an amount of

With Oleum Viticis Negundo betacyclodextrin enclose, add other each raw materials, mixing adds adjuvant, and granulation incapsulates, and get final product.

[test example]

Test the antitussive effect of 1 medicine of the present invention

1-1 is to the antitussive action of mice

Summary causes mouse cough with ammonia, and experiment is observed the antitussive action of medicine of the present invention by the number of times of coughing in mouse cough incubation period and 3 minutes.The result shows, medicine of the present invention is little, in, heavy dose of group has obvious prolongation cough latent period and reduces the cough number of times, with matched group relatively P＜0.05, P＜0.01, P＜0.001.

Purpose is observed medicine of the present invention to the antitussive action of ammonia induced mice.

Test material

Medicine

(1) be subjected to reagent: the extract dry powder of preparation in the Preparation Example 1, the below also is called for short medicine of the present invention.

(2) Western medicine positive control cloperastine tablet, the 10mg/ sheet is produced lot number: 030619 by Beijing dawn Pharmaceutical Co., Ltd; Valid until 200606.

(3) Chinese medicine positive control GUILONG KECHUANNING JIAONANG, 1g (crude drug)/grain (0.3g powder) is produced authentication code: the accurate word Z-11 of traditional Chinese medicines by Guilong Medicine Co., Ltd., Shanxi; Batch number: 040112; Valid until 2005.12.

(4) numb chaste tree mixture, 2.06g (crude drug)/g (cream) provides lot number by China TCM Academy of Sciences Xiyuan Hospital basic research chamber pharmacy group: 030425.

70 of animal Kunming mouses, the II level, male and female half and half, body weight 21.84 ± 1.21g is provided by Institute of Experimental Animals, Chinese Academy of Medical Sciences, licence numbering SCXK (capital) 2000-0006.

Animal feed formulation and nutrition

Rat is kept feedstuff, produces the licence numbering by Beijing section Australia feed corporation,Ltd that pulls together: moving (2000) No. 015 of capital.

Main component [Bei Jingying defends searching (1997) No. 083]:

Moisture≤9.5%, ash≤7.8%, protein 〉=7.8%, fat 〉=4.3%, crude fibre≤11.0%, lysine 〉=1.39%, egg+light propylhomoserin 0.3-0.54%, calcium: 1.0%, phosphorus: 0.54%, folic acid 21.1mg/kg, vitamin A 〉=11.4/kg, vitamin D 〉=98ug/kg, vitamin B complex 24.11-164mg/kg, heat: 4.62 thermies/kg.

The raising condition of animal

Xiyuan Hospital, Chinese Medicine Academy of China's Experimental Animal Center barrier environment Rearing facility, licence: SYXK (capital) 2003-0808.Room temperature: 22-24 ℃, relative humidity: 40 ± 5%.

Reagent ammonium hydroxide Beijing Century Red Star chemical industry Co., Ltd produces, lot number: 20030310.

Test method

Get 70 of healthy mices, be divided at random 7 groups, (1) blank group is given distilled water (25ml/kg); (2) cloperastine tablet group (12mg/kg); (3) GUILONG KECHUANNING group (2g crude drug/kg); (4) medicine small dose group of the present invention (125mg crude drug/kg); (5) (the 250mg crude drug/kg) of dosage group in the medicine of the present invention; (6) medicine of the present invention is heavy dose of organizes (the 500mg crude drug/kg); (7) numb chaste tree mixture (8g crude drug/kg).Every day with the volume gastric infusion of 25ml/kg once, for three days on end, after the last administration 30 minutes, mice is inserted the 500ml beaker, in put a cotton balls, the 1ml syringe is drawn ammonia 0.2ml injects cotton balls, be inverted rapidly beaker, cough number of times in the cough latent period of observed and recorded mice and the 3min, relatively, t checks between organizing.

Result of the test sees Table 1.

Table 1: on the impact of mice antitussive action

Annotate: compare with matched group ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001.

As seen from the table, medicine of the present invention is little, in, heavy dose of group and positive drug group cause mouse cough to ammonia, the effect of obvious prolongation cough latent period time and minimizing cough number of times is all arranged, with matched group significant difference is arranged relatively, respectively (P＜0.05, P＜0.01, P＜0.001).

Above-mentioned experimental result shows that medicine of the present invention causes mouse cough to ammonia, and the effect of obvious prolongation cough latent period and minimizing cough number of times is arranged.

1-2 is to the antitussive action of Cavia porcellus

Summary causes the guinea pig cough with the citric acid spraying, and experiment is observed the antitussive action of medicine of the present invention by the number of times of coughing in guinea pig cough's incubation period and 5 minutes.The result shows that medicine of the present invention has the cough latent period of prolongation and reduces the cough number of times, with matched group significant difference is arranged relatively, is respectively (P＜0.05, P＜0.01, P＜0.001).

Purpose causes the guinea pig cough with the citric acid spraying, observes the antitussive action of medicine of the present invention.

Test material

Medicine

(1) is subjected to reagent: the extract dry powder (following also referred to as " medicine of the present invention ") of preparation in the Preparation Example 1.

(2) Chinese medicine contrast GUILONG KECHUANNING JIAONANG, 1g (crude drug)/grain (0.3g powder) is produced authentication code: the accurate word Z-11 of traditional Chinese medicines by Guilong Medicine Co., Ltd., Shanxi; Batch number: 040112; Valid until 2005.12.

(3) Western medicine contrast cloperastine tablet, the 10mg/ sheet is produced the date of manufacture: 200306 by Beijing dawn Pharmaceutical Co., Ltd; Lot number: 030619; Valid until 200606.

70 of the purebred Cavia porcelluss of animal, the I level, male and female half and half, body weight 235.53 ± 35.88g is provided by Beijing section space animal cultivation center, licence numbering SCXK (capital) 2002-0005.

Reagent citric acid (citric acid), the Beijing Chemical Plant produces, lot number: 960904.

The apparatus air pump, 4 liter capacity glass bell jars, glass shower nozzle.

Test method

Front Cavia porcellus is pursued of experiment only places in the airtight bell jar of 4L container, pressure with (400mmHg) sprays into 17.5% citric acid soln by the glass shower nozzle, sprayed 1 minute, the cough number of times that records Cavia porcellus in 5 minutes screens, the cough number of times is less than 10 persons to be abandoned, and selects qualified Cavia porcellus and is used for experiment.Get 70 of the rear qualified Cavia porcelluss of screening, male and female half and half are divided into 7 groups at random, and (1) blank group is to distilled water (5ml/kg); (2) cloperastine tablet group (7mg/kg); (3) GUILONG KECHUANNING (1.2g crude drug/kg); (4) medicine small dose group of the present invention (308mg crude drug/kg); (5) (the 154mg crude drug/kg) of dosage group in the medicine of the present invention; (6) medicine of the present invention is heavy dose of organizes (the 77mg crude drug/kg); (7) numb chaste tree mixture (5g crude drug/kg).Every day with the volume gastric infusion of 5ml/kg once, for three days on end, matched group is to the equivalent normal saline, after the last administration 30 minutes, Cavia porcellus by only inserting in the airtight bell jar of 4L volume, is sprayed into 17.5% citric acid with the pressure of (600mmHg) by the glass shower nozzle, sprayed 1 minute, the cough latent period of observed and recorded Cavia porcellus and the number of times of coughing in 5 minutes, relatively, t checks between organizing.

Result of the test sees Table 2.

Table 2: on the impact of Cavia porcellus antitussive action

Annotate: compare with matched group ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001.

Experimental result shows, medicine of the present invention is little, in, heavy dose of group and positive drug group all have the obvious prolongation cough latent period time and reduce the effect of cough number of times, with matched group significant difference is arranged relatively, be respectively (P＜0.05, P＜0.01, P＜0.001).

The above results shows that medicine of the present invention can obviously prolong the cough latent period time and reduce the effect of cough number of times.

Test the phlegm-dispelling functions of 2 medicines of the present invention

2-1 is on the impact of the phenol red expectoration amount of mice

The summary experiment is observed the expectoration effect of medicine of the present invention by the method with the phenol red expectoration method of mice.As a result, medicine of the present invention is little, in, the effect that all has obvious promotion secretory volume to increase of heavy dose of group and positive drug group, with matched group significant difference (P＜0.05, P＜0.01, P＜0.001) is arranged relatively.Show the effect that medicine of the present invention has obvious promotion secretory volume to increase to mice phenol red output.

Purpose is with mice phenol red expelling phlegm method, observes medicine of the present invention mice phenol red output is had or not facilitation.

Test material

Medicine

(1) be subjected to reagent: the extract dry powder of preparation in the Preparation Example 1, be called for short medicine of the present invention.

(3) Western medicine contrast mucosolvan, the 30mg/ sheet, German Boehringer Ingelheim International Co., Ltd product, product batch number: 206362, lot number of the repackaged products: 030307.

Reagent

(1) phenol red 25 grams/bottle is produced lot number: 20001017 by the Beijing Chemical Plant.

(2) NaOH Beijing chemical reagents corporation produces, lot number: 040901.

70 of animal ICR kind mices, the SPF level, male and female half and half, body weight 19.03 ± 1.18g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., licence numbering SCXK (capital) 2002-0003.

The instrument ultraviolet-uisible spectrophotometer, model UV-120-02, Japanese Shimadzu company product.

Test method

Get 70 of healthy mices, be divided at random 7 groups, (1) blank group is given distilled water (25ml/kg); (2) mucosolvan group (16mg/kg); (3) GUILONG KECHUANNING JIAONANG group (2g crude drug/kg); (4) medicine small dose group of the present invention (125mg crude drug/kg); (5) (the 250mg crude drug/kg) of dosage group in the medicine of the present invention; (6) medicine of the present invention is heavy dose of organizes (the 500mg crude drug/kg): (7) numb chaste tree mixture (the 8g crude drug/kg).Every day with 25ml/kg volume gastric infusion once, for three days on end, water is can't help in fasting before the experiment, inject 5% phenol red normal saline solution 500mg/kg to mouse peritoneal after the last administration, after 30 minutes mice is put to death, back of the body position is fixing, cuts off cervical region center skin, separate trachea, cut an osculum on the trachea, No. 7 syringe needles that polish are inserted about 0.3cm in the trachea, after fixing with the silk thread ligation, the 1ml syringe is drawn the 0.5ml normal saline repeatedly wash air flue 3 times, flushing liquor is sucked in vitro, and above method repeats 3 times, adds flushing liquor in vitro with 0.1ml1mol/L NaOH, make liquid be alkalescence, be that the UV-120-02 type ultraviolet-uisible spectrophotometer of 546nm is measured optical density (OD) value at wavelength, with the phenol red standard curve of doing, calculate phenol red content (μ g/ml) according to standard curve, relatively, t checks between organizing.

Result of the test sees Table 3.

Table 3: on the mice impact of phenol red output

Annotate: compare with matched group; ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001.

As seen from the table, medicine of the present invention medicine of the present invention is little, in, heavy dose of group and positive drug group all have the increase of obvious promotion secretory volume, with matched group significant difference (P＜0.05, P＜0.01, P＜0.001) arranged relatively.

The brief summary the above results shows, the effect that medicine of the present invention has obvious promotion secretory volume to increase to mice expectorant of phenol red output.

2-2 is on the impact of Hair of Rat tubule expectoration amount

The summary experiment is observed medicine of the present invention to the expectoration effect of rat by with capillary tube expectoration method.The result shows that this medicine is respectively P＜0.05, P＜0.01, P＜0.001 to the effect that Hair of Rat tubule expectoration amount has obvious promotion secretory volume to increase.

Purpose is observed medicine of the present invention and is had or not the expectoration amount that promotes rat with capillary tube expectoration method.

Test material

Medicine

(1) be subjected to reagent: the extract dry powder of Preparation Example 1 preparation, be called for short medicine of the present invention.

70 of animal Wistar kind rats, the SPF level, male and female half and half, body weight 171.17 ± 21.66g is provided by Institute of Experimental Animals, Chinese Academy of Medical Sciences, licence numbering: SCXK (capital) 2000-0006.

Test method

Get 70 of healthy rats, be divided at random 7 groups, (1) blank group is given distilled water (10ml/kg); (2) mucosolvan group (11mg/kg); (3) GUILONG KECHUANNING JIAONANG group (1.5g crude drug/kg); (4) medicine small dose group of the present invention (87.5mg/kg); (5) dosage group (175mg/kg) in the medicine of the present invention; (6) the heavy dose of group of medicine of the present invention (350mg/kg); (7) numb chaste tree mixture (5.7g crude drug/kg).Anaesthetize with 3.5% chloral hydrate (10ml/kg) rat abdominal cavity during experiment, facing upward the position fixedly keeps flat, cut skin of neck, separate trachea, locate to prick an aperture with injection needle between two cartilages in thyroid cartilage lower edge center, then insert one of capillary glass tube, the long 5cm of capillary glass tube, interior through 0.8mm, capillary tube is inserted into just contacts inner surface of trachea, when capillary tube is full of, change again immediately one, measure first the front 1hr capillary tube expectoration amount of administration, give medicine by duodenum with the 10ml/kg volume behind the 1hr, matched group is to the equivalent normal saline, observe after the administration 1,2hr is secretory volume per hour on average, as normal value, relatively, t checks between organizing with the average secretory volume of 1hr before the administration.

Result of the test sees Table 4.

Table 4: on the impact of Hair of Rat tubule expectoration method expectoration amount (

N=10)

Annotate: compare with matched group; ^*P＜0.05, ^*P＜0.01, ^{* *}P＜0.001.

As seen from the table, medicine of the present invention is little, in, 1h, 2h all have the increase of obvious promotion rats breathing road secretory volume after heavy dose of group and the administration of positive drug group, with matched group significant difference are arranged relatively, respectively P＜0.05, P＜0.01, P＜0.001.

The brief summary the above results shows, the effect that medicine of the present invention has obvious promotion secretory volume to increase to the rats breathing road.

Test the antiasthmatic effect of 3 medicines of the present invention

The effect that 3-1 relievings asthma to panting property of Cavia porcellus due to histamine+acetylcholine

Medicine histamine+the acetylcholine of summary by the bronchoconstriction effect sucks Cavia porcellus with aeroponics, causes the Cavia porcellus rapid breathing, pants even suffocates, thereby cause Cavia porcellus to twitch, fall.Utilize this model, observe medicine of the present invention to the antiasthmatic effect of Cavia porcellus.As a result, medicine of the present invention is little, in, heavy dose of group and positive drug group organize to acecoline+phosphoric acid that Cavia porcellus pants and can obviously prolong pant incubation period and the time of falling due to the ammonia, with matched group relatively (P＜0.05, P＜0.01, P＜0.001).Show that medicine of the present invention brings out histamine and causes that Cavia porcellus pants obvious antiasthmatic effect is arranged.

Purpose is observed medicine of the present invention and cause the antiasthmatic effect that Cavia porcellus pants due to histamine.

Test material

Medicine

(3) Western medicine contrast aminophylline, 0.1g/ sheet, Zizhu Pharmaceutical Co., Ltd., Beijing's product, lot number: 20031202.

The purebred albino guinea-pig of animal, the I level, male and female half and half, body weight 169.37 ± 22.79g is provided by Beijing section space animal cultivation center, licence numbering: SCXK (capital) 2002-0005.

Reagent

(1) acecoline 1g/ bottle, Beijing chemical reagents corporation, lot number: 030211.

(2) 5g/ of histamine phosphate bottle, Chinese Academy Of Sciences, Shanghai Institute Of Biology produces numbering: 1702.

Instrument draws breathes heavily device: air compressor, glass aerosol shower nozzle, 4L glass bell jar.

Test method

Get healthy guinea pig, male and female half and half, in advance screening.Cavia porcellus by only putting into the 4L glass bell jar, is sprayed into 2% acecoline and 0.1% histamine phosphate's equivalent mixed liquor with the pressure of (400mmHg), sprayed for 20 seconds.After spraying stops, observing the incubation period (namely stopping the rear time that the tic of panting property occurs from spraying) that the tic of panting property appears in Cavia porcellus in 6 minutes, panting property tic incubation period＞120 a second person do not select.Get 70 of the qualified Cavia porcelluss of screening, be divided at random 7 groups, 10 every group, (1) matched group is to distilled water (5ml/kg); (2) aminophylline group (0.05g/kg); (3) GUILONG KECHUANNING JIAONANG group (1.2g crude drug/kg); (4) medicine small dose group of the present invention (77mg crude drug/kg); (5) (the 154mg crude drug/kg) of dosage group in the medicine of the present invention; (6) medicine of the present invention is heavy dose of organizes (the 308mg crude drug/kg); (7) numb chaste tree mixture (5g crude drug/kg).Every day, with 5ml/kg volume gastric infusion once for three days on end, matched group was to the equivalent normal saline, after the last administration 30 minutes, drew and breathed heavily experiment.With Cavia porcellus by only putting into the 4L glass bell jar, spraying into 2% acecoline+0.1% histamine phosphate's equivalent mixed liquor with the pressure of (400mmHg) sprayed for 20 seconds, observe (360 seconds) Cavia porcellus in 6 minutes and incubation period (also cite approvingly and breathe heavily incubation period) of panting property tic occurs, after namely stopping from spraying, time and the time of dropping to that the tic of panting property occurs, surpass 6 minutes with calculating in 360 seconds, relatively, t checked between experimental result was organized.

Result of the test sees Table 5.

Table 5: on the impact of the effect of panting of Cavia porcellus due to acetylcholine+histamine phosphate (n=10,

Annotate: compare with matched group: ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001.

From upper table result as seen, medicine of the present invention is little, in, heavy dose of group and positive drug group organize to acecoline+phosphoric acid that Cavia porcellus pants and can obviously prolong pant incubation period and the time of falling due to the ammonia, with matched group relatively P＜0.05, P＜0.01, P＜0.001.Its effect is better than numb chaste tree mixture group.

The brief summary experimental result shows, medicine of the present invention organizes the Cavia porcellus that causes due to the ammonia to pant to acecoline+phosphoric acid obvious antiasthmatic effect.

Test the spasmolysis of 4 medicines of the present invention

4-1 tests Cavia porcellus anaphylaxis bronchospasm

Summary after 14 days, sucks Cavia porcellus with the ovalbumin nebulization by intramuscular injection ovalbumin and lumbar injection pertussis vaccine sensitization, forms the guinea pig bronchial spasm, causes dyspnea, twitches and fall, thereby cause Cavia porcellus death.Utilize this model, observe medicine of the present invention to the spasmolysis of Cavia porcellus anaphylaxis bronchospasm.The result shows, medicine of the present invention is little, in, heavy dose of group and positive drug group can prolong anaphylaxis bronchospasm incubation period, dyspnea and tic are fallen the time, reduce the animal dead number, with matched group significant difference (respectively P＜0.05, P＜0.01, P＜0.001) is arranged relatively, heavy dose of group and positive drug treated animal death toll and matched group relatively have significant difference (respectively P＜0.05, P＜0.001).

Purpose is observed medicine of the present invention causes Cavia porcellus anaphylaxis bronchospasm to ovalbumin improvement effect.

Test material

Medicine

(1) be subjected to reagent: the extract of Preparation Example 1 preparation, its extract powder is used in experiment, is diluted to desired concn, calls medicine of the present invention in the following text.

(2) Chinese medicine contrast GUILONG KECHUANNING JIAONANG, 1g (crude drug)/grain (0.3g powder) is produced authentication code: the accurate word Z-11 of traditional Chinese medicines by Guilong Medicine Co., Ltd., Shanxi; Date of manufacture: 2004.01.01; Batch number: 040112; Valid until 2005.12.

The purebred albino guinea-pig of animal, the I level, male and female half and half, body weight 202.99 ± 12.98g is provided by Beijing section space animal cultivation center, licence numbering: SCXK (capital) 2002-0005.

Reagent

(1) antigen: ovalbumin 50g/ bottle, Sigma (dividing), Cat; A5253, the kindness AudioCodes trade in Beijing company limited.

(2) adjuvant: pertussis vaccine 30,000,000,000/ml/2ml/ props up, Nat'l Pharmaceutical ﹠ Biological Products Control Institute, lot number: 04-1.

Test method

Experiment is carried out in two steps, first with Cavia porcellus sensitization.Get 70 of healthy white purebred Cavia porcelluss, every Cavia porcellus back leg intramuscular injection ovalbumin 4mg (4% ovalbumin normal saline 0.1ml), lumbar injection pertussis vaccine 2 * 1010 thalline sensitization are injected rear 14 days for experiment simultaneously.Sensitization was divided into 7 groups at random with animal in the time of the 10th day, and 10 every group, (1) blank group is given distilled water (5ml/kg); (2) aminophylline group (0.05g/kg); (3) GUILONG KECHUANNING JIAONANG group (1.2g crude drug/kg); (4) medicine small dose group of the present invention (77mg crude drug/kg); (5) (the 154mg crude drug/kg) of dosage group in the medicine of the present invention; (6) medicine of the present invention is heavy dose of organizes (the 308mg crude drug/kg); (7) numb chaste tree mixture (5g crude drug/kg).Simultaneously with 5ml/kg volume gastric infusion, once a day, continuous 5 days, matched group is to the equivalent normal saline, after the last administration 30 minutes, Cavia porcellus by only placing in the airtight glass bell jar of 4L, was sprayed into for 5% ovalbumin solution half a minute with constant voltage (400mmHg), observe and record incubation period, dyspnea, the tic that the tic of panting property appears in (360 seconds) Cavia porcellus in 6 minutes and fall and the dead animal number.Apnea difficulty and without the tic person of falling was calculated with 360 seconds.Relatively, t checks experimental result between organizing.Dead animal number card side X ²Check.

Result of the test sees Table 6.

Table 6: on the impact (n=10 of guinea pig bronchial spasm due to the ovalbumin

Annotate: compare with matched group: ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001.

From upper table result as seen, medicine of the present invention is little, in, heavy dose of group and positive drug group can prolong anaphylaxis bronchospasm incubation period, dyspnea and tic are fallen the time, reduce the animal dead number, with matched group significant difference (respectively P＜0.05, P＜0.01, P＜0.001) is arranged relatively, heavy dose of group and positive drug treated animal death toll and matched group relatively have significant difference (respectively P＜0.05, P＜0.001).

The brief summary experimental result shows, medicine of the present invention is little, in, heavy dose of group have prolong anaphylaxis bronchospasm incubation period, effect that the time is fallen in dyspnea and tic, reduce the animal dead number, ovalbumin is caused that the anaphylaxis bronchospasm is significantly improved.

Test the antiinflammatory action of 5 medicines of the present invention

This laboratory observation rat paw edema inflammatory model due to the medicine on Carrageenan of the present invention, the result shows, medicine of the present invention is little, in, heavy dose of group cause scorching after 0.5,1,2,4,6 hour different time points the effect of obvious inflammation-inhibiting swelling is all arranged, with matched group significant difference (P＜0.05, P＜0.01, P＜0.001) is arranged relatively.

The 5-1 xylol brings out the swollen impact of mouse ear

Make a summary this laboratory observation medicine xylol of the present invention bring out the red and swollen inflammatory model of mice ear, experimental result, medicine of the present invention is little, in, heavy dose of group and positive drug group xylol induced mice ear inflammation have obvious inhibitory action, mouse right ear swelling obviously alleviates, and with matched group significant difference (respectively P＜0.05, P＜0.01, P＜0.001) is arranged relatively.Experimental result shows that each administration group xylol of medicine of the present invention brings out the red and swollen model of mice ear preferably antiinflammatory action.

Purpose is observed the antiinflammatory action that medicine xylol of the present invention brings out the swollen model of mouse ear.

Test material

70 of animal Male Kunming strain mice, body weight 25.06 ± 1.14 grams, the II level is provided by Institute of Experimental Animals, Chinese Academy of Medical Sciences's breeding field, licence numbering: SCXK (capital) 2000-0006.Medicine

(1) be subjected to reagent: the extract dry powder of Preparation Example 1 preparation, call medicine of the present invention in the following text.

(3) Western medicine contrast Aspirin Enteric-coated Tablets, every 0.3g is produced lot number: 011102 by Yantai No.2 Pharmaceutical Factory.Be assigned to into desired concn with distilled water during the said medicine experiment.

Test method

Get 70 of healthy mices, be divided at random 7 groups, 10 every group.(1) contrast normal saline group (25ml/kg); (2) aspirin group (0.2g/kg); (3) GUILONG KECHUANNING JIAONANG group (2g crude drug/kg); (4) medicine small dose group of the present invention (125mg/kg); (5) dosage group (250mg/kg) in the medicine of the present invention; (6) the heavy dose of group of medicine of the present invention (500mg/kg); (7) numb chaste tree mixture (8g crude drug/kg).Every day with 25ml/kg volume gastric infusion once, successive administration 3 days, matched group is to the equivalent normal saline.After administration in the 3rd day, dimethylbenzene 0.05ml dripped in mouse right ear in 30 minutes, animal is put to death in dislocation after 15 minutes, punch along left and right sides auricle same area with the 6mm card punch, the both sides auricle is weighed respectively with electronic scale, the auris dextra sheet of every Mus heavily deducts left auricle and heavily is swelling (mg), organize an ear swelling degree (mg) relatively, the t check.

Result of the test sees Table 7.

Table 7: the impact (n=10 that medicine xylol induced mice ear of the present invention is swollen

Annotate: compare with matched group ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001.

It is as shown in the table, control group mice auris dextra obvious tumefaction, and thickness increases, two auricle obvious differences.Medicine of the present invention is little, in, heavy dose of group and positive drug group xylol induced mice ear inflammation have obvious inhibitory action, mouse right ear swelling obviously alleviates, and with matched group significant difference (respectively P＜0.05, P＜0.01, P＜0.001) is arranged relatively.Experimental result shows that each administration group xylol of medicine of the present invention brings out the red and swollen model of mice ear preferably antiinflammatory action.

Brief summary

Experimental result shows, in the medicine of the present invention, heavy dose of group xylol brings out the red and swollen inflammatory model of mice ear that obvious inhibitory action is arranged.

The impact of rat paw edema due to the 5-2 on Carrageenan

Rat paw edema inflammatory model due to the medicine on Carrageenan of the present invention of having made a summary this laboratory observation, the result shows, medicine of the present invention is little, in, heavy dose of group cause scorching after 0.5,1,2,4,6 hour different time points the effect of obvious inflammation-inhibiting swelling is all arranged, with matched group significant difference (P＜0.05, P＜0.01, P＜0.001) is arranged relatively.

Purpose is observed the antiinflammatory action of rat paw edema model due to the medicine on Carrageenan of the present invention.

Test material

Medicine

(3) Western medicine contrast Aspirin Enteric-coated Tablets, every 0.3g is produced lot number: 011102 by Yantai No.2 Pharmaceutical Factory.Be assigned to desired concn with distilled water during the said medicine experiment.

(5) carrageenin (CARRAGEENAN), SIGMA, lot number: 117H0151 is mixed with desired concn during experiment.

70 of animal Wistar kind male white rats, body weight 157.05 ± 8.49 grams, one-level is provided by Institute of Experimental Animals, Chinese Academy of Medical Sciences, licence numbering: SCXK (capital) 2000-0006.

Test method

Get 70 of healthy rats, be divided at random 7 groups, (1) blank group is given distilled water (10ml/kg); (2) aspirin group (150mg/kg); (3) GUILONG KECHUANNING JIAONANG group (1.5g crude drug/kg); (4) medicine small dose group of the present invention (87.5mg/kg); (5) dosage group (175mg/kg) in the medicine of the present invention; (6) the heavy dose of group of medicine of the present invention (350mg/kg); (7) numb chaste tree mixture (5.7g crude drug/kg).Measure every left back sufficient volume of animal (ml) as being worth before the medicine with capillary tube measurement by magnification method.Every day is with 10ml/kg volume gastric infusion, once a day, successive administration 3 days, matched group gives the equal-volume normal saline, after the last administration, 1% chondrus ocellatus Holmes only caused inflammation at the left sufficient sole of the foot subcutaneous injection 0.05ml/ of section of rat in 30 minutes, mensuration cause scorching after 0.5,1,2,4, the left back sufficient volume of 6hr rat (ml) so that between difference is organized before and after scorching relatively, the t check.

Result of the test sees Table 8.

Table 8: the impact of rat paw edema due to the on Carrageenan (n=10,

Annotate: compare with matched group: ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001.

It is as shown in the table, medicine of the present invention is little, in, heavy dose of group and positive drug group cause scorching after 0.5,1,2,4,6 hour different time points the effect of obvious inhibition rat paw position swelling is all arranged, with matched group significant difference (P＜0.05, P＜0.01, P＜0.001) is arranged relatively.Brief summary

The result shows, medicine of the present invention is little, in, the rat paw edema inflammation has obvious inhibitory action due to heavy dose of group on Carrageenan.

Test the refrigeration function of 6 medicines of the present invention

6-1 medicine of the present invention is on the impact of fever in rabbits due to the escherichia coli endotoxin

Escherichia coli endotoxin pyrogenicity method is adopted in the summary experiment, injects the rabbit auricular vein with the 250ng/ml/kg endotoxin and causes heating.As a result, reached the peak, descended gradually in 6 hours in 3 hours.Aspirin group antipyretic effect is the most obvious, after the pyrogenicity 1-6 hour with matched group significant difference (P＜0.01～P＜0.001) is more all arranged; 2-6 hour antipyretic effect is obvious after heavy dose of group pyrogenicity, and effect in 4 hours is stronger, with matched group comparing difference aobvious (P＜0.05～P＜0.01); In, the small dose group antipyretic effect is not obvious.Experimental result shows that the heavy dose of group of medicine of the present invention has the trivial solution heat effect to rabbit escherichia coli endotoxin pyrogenicity.

Purpose is observed medicine of the present invention to the refrigeration function of rabbit behind auricular vein Escherichia Coli Injection endotoxin pyrogenic.

Test material

Medicine

(1) medicine of the present invention: the extract dry powder of Preparation Example 1 preparation, preparation desired concn during experiment.

(2) Aspirin Enteric-coated Tablets, the 0.3g/ sheet is produced lot number: 980808 by Hunan pharmaceutical factory.

(3) Chinese medicine contrast GUILONG KECHUANNING JIAONANG, 1g (crude drug)/grain (0.3g powder) is produced authentication code: the accurate word Z-11 of traditional Chinese medicines by Guilong Medicine Co., Ltd., Shanxi; Batch number: 040112; Valid until 2005.12.

The pyrogen escherichia coli endotoxin, 500 micrograms/, Ministry of Public Health institute of biological products, lot number: 891-2.

56 of animal large ear rabbits, female, male half and half, body weight 1.95 ± 0.19kg, tonneau laboratory animal plant provides by the Xueyaun Road, Haidian District, Beijing City, the quality certification number: the capital is moving is betrothed to (2000) No. 024 total No. 069.

Test method

Large ear rabbit is divided into 7 groups, 8 every group, male and female half and half.(1) model control group is to physiological water (3ml/kg), (2) aspirin group (100mg/kg), (3) GUILONG KECHUANNING JIAONANG (0.7g crude drug/kg), (4) the heavy dose of group of medicine of the present invention (185mg/kg), (5) dosage group (92.5mg/kg) in the medicine of the present invention, (6) medicine small dose group of the present invention (46.25mg/kg); (7) numb chaste tree mixture (3g crude drug/kg).Escherichia coli endotoxin pyrogenicity method is adopted in test, experiment the previous day with rabbit by only measuring anus body temperature twice, be averaged body temperature as medicine before body temperature.Next day gastric infusion, once a day, successive administration 3 days, model control group gives to gavage the equal-volume normal saline, gastric infusion is once before endotoxin injection for the aspirin group.Each administration group after the last administration 30 minutes through auricular vein Escherichia Coli Injection endotoxin 250ng/ml/kg, measures 1,2,3,4,5,6hr body temperature, calculates the variation (Δ ℃) of each time point body temperature, between organizing relatively, the t check.

Result of the test

Table 9: medicine of the present invention on the impact of rabbit body temperature (n=8,

Annotate: compare with matched group ^*P＜0.05, ^*P＜0.01, ^{* *}P＜0.001.

Self compares: ^#P＜0.05; ^##P＜0.01; ^###P＜0.001.

As seen from the above table, 1 hour body temperature begins to rise after the matched group pyrogenicity, reaches the peak, descends gradually in 6 hours in 3 hours.Aspirin group antipyretic effect is the most obvious, after the pyrogenicity 1-6 hour with matched group significant difference (P＜0.01～P＜0.001) is more all arranged; 2-6 hour antipyretic effect is obvious after heavy dose of group pyrogenicity, and effect in 4 hours is stronger, with matched group comparing difference remarkable (P＜0.05～P＜0.01); In, the small dose group antipyretic effect is not obvious.

Brief summary

The heavy dose of group of medicine of the present invention causes that to escherichia coli endotoxin rabbit fever models has the trivial solution heat effect.

6-2 medicine of the present invention is on the impact of rat yeast pyrogenicity

Rat yeast pyrogenicity method is adopted in this experiment of making a summary, and observes the refrigeration function of medicine of the present invention.Experimental result, 2 hours temperature declines after the model control group pyrogenicity, 3 hours begin to rise, and 4～5 reach the peak, descend gradually in 6 hours.Aspirin group antipyretic effect is obvious, after the pyrogenicity 2-9 hour with matched group significant difference (P＜0.01～P＜0.001) is more all arranged; 3-7 hour antipyretic effect is obvious after heavy dose of group pyrogenicity, with matched group significant difference (P＜0.05) is arranged relatively; 3-5 hour and matched group comparison (P＜0.05) after the middle dosage group pyrogenicity; The small dose group antipyretic effect is not obvious; 3-5 hour and matched group comparison (P＜0.05) after the GUILONG KECHUANNING JIAONANG group pyrogenicity; Experimental result shows, the big or middle dosage group of aspirin group, GUILONG KECHUANNING JIAONANG group and medicine of the present invention has the trivial solution heat effect to rat fever due to the yeast, and heavy dose of group antipyretic effect time of medicine of the present invention is longer than numb chaste tree mixture group.The result shows that the big or middle dosage group of medicine of the present invention can obviously reduce the rat temperature rising that yeast causes, preferably refrigeration function is arranged.Purpose is brought out pyrogenicity to rat skin lower injection yeast suspension, observes medicine of the present invention to the refrigeration function of rat.

Test material

Medicine

(1) medicine of the present invention: the extract dry powder of Preparation Example 1 preparation is mixed with desired concn during experiment.

70 of animal SD kind rats, the SPF level, body weight 189.5 ± 5.57g, male and female half and half are provided by Beijing Vital River Experimental Animals Technology Co., Ltd., licence numbering SCXK (capital) 2002-0003.

Test method

Animal is divided into 7 groups at random, and 10 every group, male and female half and half.(1) model control group is to physiology salt (10ml/kg); (2) aspirin group (0.15g/kg); (3) GUILONG KECHUANNING JIAONANG group (1.5g crude drug/kg); (4) the heavy dose of group of medicine of the present invention (350mg/kg); (5) dosage group (175mg/kg) in the medicine of the present invention; (6) medicine small dose group of the present invention (87.5mg/kg); (7) numb chaste tree mixture (5.7g crude drug/kg).The previous day is measured rat anus body temperature twice in test, be averaged body temperature as medicine before body temperature.Every day gastric infusion once, for three days on end, model control group is given and to be gavaged the equal-volume normal saline, each administration group after the last administration 30 minutes, at rat back subcutaneous injection 15% yeast suspension (10ml/kg), gastric infusion is once before injection yeast suspension for the aspirin group.Measure each administration group 2,3,4,5,6,7,8,9hr rat temperature, 4hr after pyrogenicity, each administration group is gastric infusion once (dosage is the same) again, calculates the variation (Δ ℃) of each time point body temperature, between organizing relatively, the t check.

Result of the test

Table 10: medicine of the present invention on the impact of rat temperature (n=10,

Annotate: compare with model control group: ^*P＜0.05; ^*P＜0.01; ^{* *}P＜0.001.

Self compares: ^##P＜0.01; ^###P＜0.001.

By table as seen, 2 hours temperature declines after the model control group pyrogenicity, 3 hours begin to rise, and 4～5 reach the peak, descend gradually in 6 hours.Aspirin group antipyretic effect is obvious, after the pyrogenicity 2-9 hour with matched group significant difference (P＜0.01～P＜0.001) is more all arranged; 3-7 hour antipyretic effect is obvious after heavy dose of group pyrogenicity, with matched group significant difference (P＜0.05) is arranged relatively; 3-5 hour and matched group comparison (P＜0.05) after the middle dosage group pyrogenicity; The small dose group antipyretic effect is not obvious; 3-5 hour and matched group comparison (P＜0.05) after the GUILONG KECHUANNING JIAONANG group pyrogenicity; Experimental result shows, the big or middle dosage group of aspirin group, GUILONG KECHUANNING JIAONANG group and medicine of the present invention has the trivial solution heat effect to rat fever due to the yeast, and heavy dose of group antipyretic effect time of medicine of the present invention is longer than numb chaste tree mixture group.

Yeast rat fever model is adopted in this experiment of brief summary, observes the refrigeration function of medicine of the present invention.The result shows that the big or middle dosage group of medicine of the present invention can obviously reduce the rat temperature rising that yeast causes, preferably refrigeration function is arranged.

Test the enhancing immunization of 7 Chinese medicine extract of the present invention

7-1 is on the impact (nonspecific immunity) of mice phagocytic function

Summary is observed medicine of the present invention to the impact of mouse monokaryon cytophagy with the carbon clearance method.The result shows, positive control drug levamisole and GUILONG KECHUANNING JIAONANG group carbon clearance index are apparently higher than matched group, compare P＜0.05, P＜0.01 with matched group, medicine of the present invention is heavy dose of, middle dosage group mice carbon clearance index is higher than matched group, significant difference P＜0.05, P＜0.01 are arranged, show that the big or middle dosage group of this medicine and positive control drug have obvious potentiation to nonspecific immunity of mice, its effect is better than numb chaste tree mixture group.

Purpose utilizes the carbon clearance method to observe medicine of the present invention to the effect of mouse monokaryon cytophagy.

Test material

Medicine

(1) be subjected to reagent: the extract dry powder of Preparation Example 1 preparation, experiment is assigned to desired concn with distilled water with extract powder.

(2) Chinese medicine contrast GUILONG KECHUANNING JIAONANG, 1g (crude drug)/grain (0.3g powder) is produced authentication code: the accurate word Z-11 of traditional Chinese medicines by Guilong Medicine Co., Ltd., Shanxi; Batch number: 040112; Valid until 2005.12, be assigned to desired concn during experiment.

(3) Western medicine contrast levamisole hydrochloride, 25mg/ sheet, BJ Pharmaceutical Co., Ltd. product, lot number: 9608228.Be assigned to desired concn during experiment.

(5) india ink, chemical plant in the West Beijing, lot number: 820501.

70 of animal health ICR kind mices, the SPF level, male and female half and half, body weight 19.21 ± 1.24 grams are provided credit number SCXK (capital) 2002-0003 by Beijing Vital River Experimental Animals Technology Co., Ltd..

Test method

Get 70 of mices, be divided at random 7 groups, 10 every group, (1) matched group is to distilled water (25ml/kg); (2) levamisole group (30mg/kg); (3) GUILONG KECHUANNING JIAONANG group (2g crude drug/kg): (4) medicine small dose group of the present invention (125mg/kg); (5) dosage group (250mg/kg) in the medicine of the present invention; (6) the heavy dose of group of medicine of the present invention (500mg/kg); (7) numb chaste tree mixture (8g crude drug/kg).With 25ml/kg volume gastric infusion once give continuously 7 days every day, and matched group is given with the volume normal saline, only gave mouse tail vein injection with 10% india ink 0.2ml/ in 30 minutes after the last administration.The eyeball rear vein beard was got blood 0.02ml respectively rear 2 minutes of injection and 10 minutes, join lysed erythrocyte in the test tube that the 4ml distilled water is housed, then be UV-120-02 type spectrophotometric determination optical density (OD) value of 600nm at wavelength, calculate within the unit interval speed K of carbon clearance in the serum by following formula.

K = \frac{\log OD 2 - \log OD 10}{t 10 - t 2}

OD2 and OD10 injected respectively behind the india ink 2 minutes and the OD value of 10 minutes institute's blood samplings, and t2 and t10 are for getting the blood time.Relatively, t checks result of the test between organizing.

Result of the test the results are shown in Table 11.

Table 11: medicine of the present invention is on the impact (n=10 of mice phagocytic function

It is as shown in the table, positive control drug levamisole and GUILONG KECHUANNING JIAONANG group carbon clearance index are apparently higher than matched group, compare P＜0.05, P＜0.01 with matched group, medicine of the present invention is heavy dose of, middle dosage group mice carbon clearance index is higher than matched group, significant difference P＜0.05, P＜0.01 are arranged, show that the big or middle dosage group of this medicine and positive control drug have obvious potentiation to nonspecific immunity of mice, its effect is better than numb chaste tree mixture group.

Brief summary

With the carbon clearance test method, observe medicine of the present invention to the impact of mice serum carbon clearance speed.Experimental result, this medicine has obvious potentiation to nonspecific immunity of mice.

7-2 is on the allergic impact of mice Delayed onset (cellular immunization)

The summary experiment causes mice Delayed onset allergic disease model with DNF, observes medicine of the present invention to the effect of mice Delayed onset allergy (DTH).Each dosage group of medicine of the present invention causes mice Delayed onset allergic disease model mice ear not obvious to DNF, spleen, thymus index are changed not obvious, with matched group no significant difference relatively.The result shows that this medicine suppresses or potentiation without obvious mice Delayed onset allergy.

Purpose to mouse sensitization, is observed medicine of the present invention is attacked caused Delayed onset allergy (DTH) to accepting this antigen effect take DNF as antigen, to inquire into this medicine to the impact of mouse cell immunologic function.

Test material

Medicine

(3) Western medicine contrast levamisole hydrochloride: 25mg/ sheet, BJ Pharmaceutical Co., Ltd. product, lot number: 9608228.Be assigned to desired concn during experiment.

70 of animal health ICR kind mices, the SPF level, male and female half and half, body weight 19.9 ± 0.84g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., credit number SCXK (capital) 2002-0003.

Test method

Get 70 of mices, be divided at random 7 groups, 10 every group, (1) matched group is to distilled water (25ml/kg); (2) levamisole group (30mg/kg); (3) GUILONG KECHUANNING JIAONANG group (2g crude drug kg); (4) medicine small dose group of the present invention (125mg/kg); (5) dosage group (250mg/kg) in the medicine of the present invention; (6) the heavy dose of group of medicine of the present invention (500mg/kg); (7) numb chaste tree mixture (8g crude drug/kg).Every day with 25ml/kg volume gastric infusion once, continuous 8 days, matched group is given with the volume normal saline, in administration the 3rd day except matched group, each administration group mice evenly is applied in abdominal part depilation place sensitization 1 time with 1%DNFB acetone olive oil solution 50 μ l, about 3 * 3 (cm) 2 of area, the 5th day each treated animal is applied in the mouse right ear two sides with the same antigen 10 μ l and attacks after sensitization.24h after attacking puts to death the dislocation of mice cervical vertebra, cuts left and right sides auricular concha, takes off the auricle of diameter 8mm with card punch, weighs.The difference of left and right sides auricle weight is swelling (FPR), with the degree of expression Delayed onset allergy (DTH), gets thymus simultaneously, spleen is weighed, and calculates internal organs mg/10g body weight, between the result organizes relatively, the t check.

Result of the test the results are shown in Table 12.

Table 12: on the impact (n=10 of mouse cell immunologic function

Annotate: compare with matched group ^*P＜0.05; ^*P＜0.01.

It is as shown in the table, and each dosage group of medicine of the present invention is to causing mice Delayed onset allergic disease model mice ear not obvious with DNF, spleen, thymus index are changed not obvious, with matched group no significant difference relatively.The result shows that this medicine suppresses or potentiation without obvious mice Delayed onset allergy.

Brief summary

With the allergic method of Delayed onset, observe medicine of the present invention to the allergic effect of mice Delayed onset, the result shows that this medicine suppresses or potentiation without obvious mice Delayed onset allergy.

7-3 is on the impact (humoral immunization) of mice serum agglutinin

Summary is used the agglutinin method for measuring, observes medicine of the present invention to the impact of mouse humoral immune function.As a result, level and matched group that the heavy dose of group of medicine of the present invention all improves anti-sheep red blood cell antibody in the mice serum significantly compare P＜0.05, P＜0.01, and show obvious dose-effect relationship.Prompting, the heavy dose of group of medicine of the present invention is improved the effect of mouse humoral immune function.

Purpose is observed medicine of the present invention to the impact of mouse humoral immune function by the effect to the mice serum agglutinin.

Test material

Medicine

(1) be subjected to reagent: the extract dry powder of Preparation Example 1 preparation, experiment is prepared desired concn with distilled water with extract powder.

(3) Western medicine contrast levamisole hydrochloride tablets: 25mg/ sheet, BJ Pharmaceutical Co., Ltd. product, lot number: 9608228.

Animal ICR kind mice, male and female half and half, the SPF level, body weight 19.80 ± 0.79g is provided by Beijing Vital River Experimental Animals Technology Co., Ltd., credit number: SCXK (capital) 2002-0003.

Test method

Get 84 of mices, be divided at random 7 groups, 12 every group, (1) matched group is to distilled water (25ml/kg); (2) levamisole group (30mg/kg); (3) GUILONG KECHUANNING JIAONANG group (2g crude drug/kg); (4) medicine small dose group of the present invention (125mg/kg); (5) dosage group (250mg/kg) in the medicine of the present invention; (6) the heavy dose of group of medicine of the present invention (500mg/kg); (7) numb chaste tree mixture (8g crude drug/kg).Every day with 25ml/kg volume gastric infusion once, successive administration 7 days, after the administration 48 hours, mouse peritoneal is injected 5% sheep red blood cell (SRBC) 0.25ml/ and is only carried out immunity, got blood by the eyeball rear vein beard in the 6th day after the immunity, centrifugal, separation of serum is measured anti-SRBC antibody titer in the serum with micro-agglutination.

The Microhemagglutination test method: with normal saline with the serum two-fold dilution, the serum of variable concentrations is drawn respectively 25 μ l to be placed in the Microhemagglutination plate hole, add again 0.5%SRBC 25 μ l, the vibration mixing places in the moistening square position and adds a cover, and puts into 37 ℃ of calorstats and hatches, observe the coagulation degree after 3 hours, divide 5 grades (0～4), by following formula calculating antibody product, result of the test t check.

Antibody product=∑ (S ₁+ 2S ₂+ 3S ₃+ ... nS _n)

In the formula 1,2,3......n represents two-fold dilution's index, S represents the rank of coagulation degree, the antibody product is larger, the expression antibody titer is higher, T check between group.

Result of the test the results are shown in Table 13.

Table 13: medicine of the present invention is to the effect (n=12 of mice serum agglutinin

Annotate: compare with matched group.

It is as shown in the table, the heavy dose of group of medicine of the present invention has all improved the level of anti-sheep red blood cell antibody in the mice serum significantly, compare (P＜0.05) with matched group, positive control drug levamisole and GUILONG KECHUANNING JIAONANG group have also significantly improved the antibody response (P＜0.05) of mice to sheep red blood cell.Prompting, the heavy dose of group of medicine of the present invention can improve the mouse humoral immune function.

Brief summary

This test agglutinin method for measuring, observe medicine of the present invention to the impact of mouse humoral immune reaction, the result shows, in the medicine of the present invention, heavy dose of group all can improve mice significantly to the antibody response (P＜0.05～P＜0.01) of sheep red blood cell.The effect that show in the medicine of the present invention, heavy dose of group is improved humoral immune function.

Test the antivirus action of 8 medicines of the present invention

8-1 is to infecting the protective effect of FM1 virus mice

Summary: medicine gastric infusion of the present invention, observe this medicine to infecting the protective effect of FM1 virus mice, the result shows: the large, medium and small dosage of medicine of the present invention all can reduce infection FM ₁The mortality rate of animal is (P＜0.01) all, prolongs life span all (P＜0.001), and heavy dose of papova Lung Index of mice infected by Influenza virus and lung inner virus content are with model group comparing difference remarkable (P＜0.05).Point out this medicine can alleviate the infecting mouse pulmonary lesion.

Purpose: this paper sets up viral pulmonary infection mouse model with Flu virus FM1 collunarium infecting mouse, take lung index, mortality rate and prolongation life span as index, observes this medicine to the protective effect of viral pulmonary infection mice.

Materials and methods

Medicine

1, be subjected to reagent: the extract dry powder of Preparation Example 1 preparation, mice dosage are 500,250,125mg/kg/ day, with distilled water be made into 50,25, the medicinal liquid of 12.5mg/ml is for subsequent use.

2, contrast medication: (1) GUILONG KECHUANNING JIAONANG, produced by Guilong Medicine Co., Ltd., Shanxi.Authentication code: (89) are defended the accurate word Z-11 of medicine number, product batch number: 030101.Dosage is 2g crude drug/kg/ day, and it is for subsequent use to be made into the 0.2g/ml medicinal liquid with distilled water.(2) Western medicine contrast medicine ribavirin injection, 100mg/ml is produced authentication code: the accurate word H19993335 of traditional Chinese medicines, product batch number: 03020137 by Yongkang, Beijing pharmaceutical factory.Dosage is 70mg/kg/ day, and it is for subsequent use to be made into the 7mg/ml medicinal liquid with distilled water.

Virus influenza virus A-prime Mus lung adapted strain (FM1): provided by Virology Inst., China Academy of Preventive Medicine Sciences, this chamber nitrogen at night is preserved.Embryo Gallus domesticus go down to posterity increase for 2 times the poison after the blood clotting titre be 1: 640, to mice LD ₅₀Be 10 ^-4.44

Embryo Gallus domesticus: 9 ages in days, bought by upper village Ji Chang.

Animal KM kind mice, secondary, body weight 12～14 gram, male and female half and half are bought by Beijing Vital River Experimental Animals Technology Co., Ltd., the quality certification number: SCXK (capital) 2002-0003.

Experimental technique:

1. mouse lung index and lung index are measured: 84 of healthy mices, divide at random 7 groups, be normal control (feedwater), virus control (feedwater), GUILONG KECHUANNING JIAONANG (560mg/kg), ribavirin (70mg/kg) and be subjected to reagent large (500mg/kg), in (250mg/kg), little (125mg/kg) dosage group, each organizes 12, male and female half and half.After infect the 5th day each treated animal self-infection the first two day is respectively with 10ml/kg gastric infusion or feedwater totally 7 days.Except normal group, each organizes mice all under the slight anesthesia of ether, respectively with 15LD ₅₀Virus 5 0ul collunarium infect, Normal group is with method collunarium normal saline 50ul.After last 1 administration 24 hours, mice was weighed, and plucked the eyeball blood-letting and caused death, and took out full lung with the sterile working and weighed, and calculated lung index and lung index.Mouse lung is made into 10% suspension through Potter-Elvehjem Tissue Grinders homogenate with normal saline, 2000 rev/mins, centrifugal 10 minutes, gets supernatant normal saline dilution 10 ^-1～10 ^-7, inoculate 9 age in days chick embryo allantois intracavity, the 0.1ml/ embryo, 5 pieces of every dilution factor inoculations were cultivated 48 hours for 33 ℃, measured hemagglutinative titer in the chick embryo allantoic liquid, pressed Reed and Muench method and calculated half infection concentration (EID ₅₀).

2. the dead protection of virus infected mice and extending life are tested: divide at random 7 groups healthy mice, and 30 of model group, all the other respectively organize 20, both normal control, virus control, GUILONG KECHUANNING JIAONANG, ribavirin and be subjected to the large, medium and small dosage group of reagent.Medication is respectively organized mice respectively with 10LD with test 1 except Normal group ₅₀Viral collunarium infect after, observe day by day the animal incidence and record death toll, totally 14 days, calculate dead protective rate and extending life rate.

The result

1. on the impact of Lung Index of mice infected by Influenza virus and lung inner virus content

(1) on the impact of Lung Index of mice infected by Influenza virus and lung inner virus content, the results are shown in Table 14-1.

Table 14-1: to the effect of Lung Index of mice infected by Influenza virus

It is as shown in the table, the enlargement of virus infected mice lung, and lung index (1.31 ± 0.25) is significantly greater than normal group (0.91 ± 0.07) (P＜0.001).The heavy dose of group of medicine of the present invention lung index obviously reduces, lung index (1.1 ± 0.14) with touch type group comparing difference significantly (P＜0.05), lung index is 16.03%.The ribavirin group has obviously reduced lung index (1.08 ± 0.09), and touches type group comparing difference significantly (P＜0.01), and lung index is 17.56%.GUILONG KECHUANNING JIAONANG is significantly effect not.

(2) on the impact of infecting mouse lung inner virus content, the results are shown in Table 14-2.

Table 14-2: lung inner virus assay (blood clotting)

It is as shown in the table, mouse infection FM ₁After the virus, model group lung inner virus content EID ₅₀Be 10 ^-5.85, and heavy dose of group EID ₅₀Be 10 ^-4.17, large 4.5 times than model group, similar to Western medicine contrast ribavirin group.

2. the dead protection of virus and extending life effect

Table 14-3: the dead protection of virus infected mice and extending life effect

Annotate: ^*P＜0.01 ^{* *}P＜0.001

It is as shown in the table, viral infection is respectively organized mice all death, virus control group mortality rate is 90%, mean survival time is 7.53 ± 2.52 days. being subjected to the large, medium and small dosage group of reagent mortality rate is 35～45%, significantly reduce (P＜0.01) with model group comparison death toll, more all there were significant differences (P＜0.001) with the virus control group for 10.9～11.7 days mean survival times and extending life rate 44.75～55.37%.The western medicine group mortality rate is 10%, and more all there were significant differences (P＜0.001) with the virus control group for 13.5 ± 1.57 days mean survival times and extending life rate 79.28%.GUILONG KECHUANNING JIAONANG is not as good as medicine of the present invention.

Brief summary

Medicine of the present invention is pressed the variable concentrations gavage to the mice of influenza virus infection FM1, observe this medicine to the dead protective effect of infecting mouse and the inhibitory action of pulmonary lesion.The result shows, the large, medium and small dosage group of this medicine all can reduce the dead number average (P＜0.01) of infection animal, prolong life span all (P＜0.001), heavy dose of group lung index and model group comparing difference be (P＜0.05) significantly, lung index 16.03%, lung inner virus content reduces than model group, illustrates that this medicine can suppress FM in Mice Body ₁Virus replication alleviates pulmonary lesion.

8-2 medicine of the present invention suppresses the experimentation of influenza virus effect

Summary: medicine of the present invention adopts Various medications, observes the protective effect of this medicine infected by influenza first 3, B-mode infection Embryo Gallus domesticus, and the result shows that this medicine infected by influenza has direct deactivation.

Purpose: this paper sets up viral infection and touches type with influenza virus A 3, B-mode infection Embryo Gallus domesticus, and viral level is the inhibitory action of this medicine infected by influenza of index observing in the chick embryo allantoic liquid.

Materials and methods

Medicine

1. test medication: Chinese medicine extraction dry powder liquirtin, Herba Ephedrae total alkali, baicalin, Oleum Viticis Negundo were by 2.5: 1: 2.5: 0.04 weight ratio is mixed with.

Experimental drug prepares: add each dry powder dissolving after Oleum Viticis Negundo is dissolved in dimethyl sulfoxide, total amount 4.5ml is equivalent to 257mg/ml, puts 4 ℃ of refrigerators (calling medicine of the present invention in the following text) for subsequent use.

2. contrast medication: GUILONG KECHUANNING JIAONANG, 3g crude drug/g medicated powder is produced by Guilong Medicine Co., Ltd., Shanxi.Authentication code: (89) are defended the accurate word Z-11 of medicine number, product batch number: 030101.

GUILONG KECHUANNING JIAONANG 3g medicated powder is got in the experimental drug preparation, adds the 20ml dissolved in distilled water, and water-bath was boiled 20 minutes, and cool rear 2000 rev/mins, centrifugal 10 minutes, get supernatant 14ml, be equivalent to 0.7g crude drug/ml, 5.6%NaHCO is used in 4 ℃ of preservations before the experiment ₃Transfer PH=7.2.

Virus

1, influenza first 3 types: the 95-359 chick embryo allantoic liquid prevented in the Chinese.

2, influenza B: the 93-184 chick embryo allantoic liquid is prevented in the capital.

Provided by Virology Inst., China Academy of Preventive Medicine Sciences, during experiment with 50～100EID ₅₀/ 0.1ml.

3, Embryo Gallus domesticus: instar chicken embryo on the 9th～10 is provided by upper village Ji Chang.

Experimental technique:

1. medicine is to the toxicity test of Embryo Gallus domesticus: will dilute the capable chick embryo allantoic cavity inoculation of good medicinal liquid 0.1ml, and cultivate 72 hours in 33 ℃ of incubators, and observe Embryo Gallus domesticus every day anyway.

2. medicine and viral equivalent neutralisation: will dilute good medicinal liquid and neutralize at the test tube moderate with virus; Put 33 ℃ of incubators 1 hour, row chick embryo allantoic cavity inoculation 0.2ml.Cultivate in 33 ℃ of incubators.

3. dose regimen behind the first virus inoculation: the 0.1ml virus inoculation was put 33 ℃ of incubators 1 hour in chick embryo allantoic cavity, adopted with the good medicinal liquid 0.1ml of approach injection dilution again, cultivated in 33 ℃ of incubators.

More than virus control is done in experiment simultaneously, observes Embryo Gallus domesticus every day, meets extremely then and removes.First 3 types were cultivated 48 hours, B-mode cultivation 72 hours, put 4 ℃ of refrigerator overnight after, get allantoic fluid and survey hemagglutinative titer (HA), the difference of comparative experiments group and virus control group.Press Reed and muench method and calculate half toxic concentration and half protection concentration (in and concentration).Formula is as follows:

The result

1. medicine is to the toxicity test of Embryo Gallus domesticus

The results are shown in Table 15-1.

Table 15-1: medicine is to the toxicity test result of Embryo Gallus domesticus

As show shown in the 15-1, the maximal non-toxic concentration of medicine of the present invention is 32.125mg/ml, GUILONG KECHUANNING JIAONANG maximal non-toxic concentration is 700mg/ml.

2. medicine and influenza virus A 3 type equivalent neutralizations

The results are shown in Table 15-2.

Table 15-2: medicine and influenza virus A 3 type equivalent neutralization results (HA)

As show shown in the 15-2, medicine of the present invention in the average half of first 3 type viruses and concentration be 0.011mg/ml, neutralization index is 6617.69.In the average half of GUILONG KECHUANNING JIAONANG and concentration be 9.47mg/ml, neutralization index is 99.81.In can be fully and influenza first 3 types virus.

3. the B-mode equivalent neutralization of medicine and influenza virus

The results are shown in Table 15-3.

Table 15-3: the B-mode equivalent neutralization of medicine and influenza virus result

As show shown in the 15-3, medicine of the present invention in the average half of influenza B virus and concentration be 0.018mg/ml, neutralization index is 4022.2.In the average half of GUILONG KECHUANNING JIAONANG and concentration be 236.46mg/ml, neutralization index is 3.99.In can be fully and influenza B virus.

4. the medicine infected by influenza infects the protective effect of Embryo Gallus domesticus

The results are shown in Table 15-4.

Table 15-4: the medicine infected by influenza infects the protective effect result of Embryo Gallus domesticus

It is as shown in the table for table 15-4, and infected by influenza infected Embryo Gallus domesticus when drug level of the present invention was 32.125mg/ml does not have protective effect.

Brief summary

With the direct inactivation of viruses method of medicine and Antiviral Effect activation measurement, observe these medicine infected by influenza first 3 types, B-mode effect.The result shows, this medicine is in the average half of first 3 types and concentration 0.011mg/ml, and in the B-mode average half and concentration 0.018mg/ml, infected by influenza infects Embryo Gallus domesticus does not have protective effect.Results suggest, this medicine infected by influenza has neutralization, does not have therapeutical effect.

Test the antibacterial actions of 9 medicines of the present invention

9-1 medicine of the present invention is to the In-vitro Inhibitory Effect of common pathogen

Summary is measured medicine of the present invention to the inhibitory action of 8 kind of 53 strain common pathogen with test tube liquid diluting method.The result shows that this medicine is 100% to the suppression ratio of staphylococcus aureus, staphylococcus epidermidis, streptococcus, escherichia coli, micrococcus catarrhalis, pneumobacillus and Bacillus proteus, is 75% to the suppression ratio of bacillus pyocyaneus, and total suppression ratio is 98.1%, MIC ₅₀Be 2.59mg/ml.

Purpose is measured this medicine to the bacteriostasis of common pathogen with external tube dilution method.

Materials and methods

Strain

This test pathogenic strain of clinical separation, comprise each 1 strain of staphylococcus aureus 9 strains, staphylococcus epidermidis 10 strains, streptococcus 8 strains, micrococcus catarrhalis 3 strains, pneumobacillus 6 strains, bacillus pyocyaneus 3 strains, Bacillus proteus 5 strains, Escherichia coli 6 strains and staphylococcus aureus, bacillus pyocyaneus and escherichia coli Quality Control strain, totally 53 strains provide by Inst. of Medicinal Biological Technology, Chinese Academy of Medical Sciences.

Medicine

Experimental drug (following abbreviation medicine of the present invention) is by liquirtin, the Herba Ephedrae total alkali, and baicalin, Oleum Viticis Negundo, by 2.5: 1: 2.5: 0.04 part by weight mixed and forms.Contrast medicine SHUANGHUANGLIAN KOUFUYE, 1.5g crude drug/ml, He'nan Zhulin Zhongsheng Pharmaceutical Industry Co. Ltd, lot number: 03051611.Be made into the medicinal liquid of 1g crude drug/ml concentration with distilled water, for subsequent use after 100 ℃ of sterilizations in 30 minutes.

Culture medium

Nutrient broth dry powder, Beijing is logical sequence Deco skill centre of development import packing (U.S. ATCC) not, lot number: 20010210.M-H fluid medium dry powder, ministry of Health of China pharmaceutical biological product calibrating institute product, lot number: 000104, be used for bacteriostatic test.

More than two kinds of dry powder be mixed with according to operation instructions that to put refrigerator after the culture medium for subsequent use.

5% horse serum meat soup: the cultivation and the bacteriostatic test that add aseptic horse serum to 5% concentration first, the group B streptococcus of deactivation in above-mentioned two kinds of culture medium.

Horse serum: Beijing medical officer veterinary's centre of prevention and cure product, lot number: 950520.

4. cosolvent: dimethyl sulfoxide, the sharp chemical reagent company limited product of Beijing benefit, lot number: 20041110.

Method

It is 32mg/ml that said medicine is mixed with final concentration, and dilution is 16,8,4,2,1 and the medicinal liquid of 7 concentration of 0.5mg/ml successively; The dilution of contrast medicine SHUANGHUANGLIAN KOUFUYE is 100,50,25,12.5,6.25,3.125,7 concentration of 1.56mg/ml, add successively in the aseptic small test tube of having got ready the medicinal liquid of each concentration respectively, the 1ml/ pipe, each 54 row, last 1 row is not for adding the medicine contrast of antibacterial.The dimethyl sulfoxide of establishing in addition 2% and 4% concentration is the substrate contrast, 54 pipes of each packing.

The fresh bacterial cultures of dilution in 1: 1000 is joined 0.1ml/ pipe in the good pastille test tube of above-mentioned each row's dilution, and other establishes each bacterial strain control tube of not dosing.First, second streptococcus is put 5%CO ₂, cultivated 20 hours in 37 ℃ of calorstats, other each bacterium is put and cultivates observed result after 20 hours in 37 ℃ of incubators.Minimum dilution drug level without bacterial growth is minimal inhibitory concentration (MIC).In this test, IC＞I00mg/ml is decided to be without bacteriostasis, calculates total suppression ratio and MIC ₅₀

The result

Test with each bacterial strain well-grown in corresponding culture medium, the dimethyl sulphoxide control pipe of 2% and 4% concentration is on the not impact of growth of each bacterial strain, and strain growth is good.The culture medium of pastille is all without bacterial growth.Result of the test sees Table 16-1.

Table 16-1: medicine of the present invention is to the inhibitory action result of antibacterial

It is as shown in the table, and medicine of the present invention is except being 75% to the bacillus pyocyaneus suppression ratio, and other strain suppression ratio are 100%, and total suppression ratio of medicine of the present invention is 98.1%, MIC ₅₀Be 2.59mg/ml.

Table 16-2: SHUANGHUANGLIAN KOUFUYE is to the inhibitory action result of antibacterial

It is as shown in the table, SHUANGHUANGLIAN KOUFUYE has inhibitory action to staphylococcus aureus (100%), staphylococcus epidermidis (60%), streptococcus (50%), micrococcus catarrhalis (100%), pneumobacillus (16.7%), escherichia coli (71.4%), Bacillus proteus (60%), and bacillus pyocyaneus is not had inhibitory action, total suppression ratio is 60.4%, MIC ₅₀Be 20.61mg/ml.The result shows that vitro Drug bacteriostasis of the present invention is better than contrasting the medicine SHUANGHUANGLIAN KOUFUYE.

Brief summary

This paper liquid tube dilution method has been measured medicine of the present invention to the inhibitory action of 8 kind of 53 strain bacterial strain, and the result shows that total suppression ratio is 98.1%, LD ₅₀Concentration is 2.59mg crude drug/ml.This medicine In Vitro Bacteriostasis is better than contrasting the medicine SHUANGHUANGLIAN KOUFUYE.

9-2 medicine of the present invention is to the protective effect of infection of staphylococcus aureus mice

Summary with staphylococcus aureus with 95% fatal dose to the mouse peritoneal infectable infection after, observe this medicine to the protective effect of infected mice.The result shows that this medicine heavy dose has significant protective effect (P＜0.05) to the infection of staphylococcus aureus mice.

Purpose is observed this medicine to the protective effect of infection animal with staphylococcus aureus after to the mouse peritoneal infectable infection.

Materials and methods

It is the Chinese medicine extraction dry powder (calling medicine of the present invention in the following text) of preparation in the Preparation Example 1 that medicine is subjected to reagent.The mice dosage is 500,250,125mg/kg/ day, Chinese medicine contrast GUILONG KECHUANNING JIAONANG, is produced by Guilong Medicine Co., Ltd., Shanxi.Authentication code: (89) are defended the accurate word Z-11 of medicine number, product batch number: 030101, and the mice dosage is 2g (crude drug)/kg/ day.Western medicine contrast Cefradine Capsules, authentication code: the accurate word H11221429 of traditional Chinese medicines, product batch number: 041003, adult's dosage 1.5g/70kg/ day, mice dosage 0.2g/kg.

Strain is provided by the first clinical hospitals clinical laboratory of Beijing Medical University from the pathogenic staphylococcus aureus (1044) of clinical patient separation and Culture.Diluting with 5% gastric Mucin before use being inoculated in the fresh cultured thing of cultivating 18 hours in the M-H culture medium.LD to mice ₉₅Be 10 ^-1.4

Culture broth culture medium dry powder, Beijing be logical sequence Deco skill centre of development product not, lot number: 20010210, and it is for subsequent use to put refrigerator after the by specification preparation.

Gastric Mucin capsule: for improving the virulence usefulness of bacterial strain, the flourish high Biochem Pharma Inc in Chongqing product, lot number: 04201.Be made into the gastric Mucin of 5% concentration with normal saline, for subsequent use through 10 pounds of sterilizations in 20 minutes.

90 of animal health ICR mices, male and female half and half, body weight 18～22g is provided by Beijing dimension tonneau China Experimental Animal Center.Licence numbering: SCXK11-00-0008.

Method is divided 6 groups at random with experimental animal, and namely antibacterial infects 20 of matched groups (abbreviation infected group), Western medicine contrast Cefradine Capsules, Chinese medicine contrast GUILONG KECHUANNING JIAONANG, big or middle each 14 of small dose group, the male and female half and half of reaching of medicine of the present invention.Infect beginning in front 7 days with the volume gastric infusion of 10ml/kg, 1 time on the 1st, continuous 7 days.After the last administration, dyed with 0.6ml/ dosage lumbar injection staphylococcus aureus bacterium liquid inductance only respectively in 1 hour, observe day by day animal dead, check the difference that compares between administration group and the infected group through x2, and calculate mortality rate.

The result

The results are shown in Table 16-3.

Table 16-3: medicine of the present invention is to the protective effect of infection of staphylococcus aureus animal

From table 16-3 result as seen, animal because of the infection Post-dead duration all in 72 hours, dead animal continues to observe and 1 week occurred dead again in 72 hours.Infect matched group 95% animal dead in 72 hours.The positive control drug Cefradine Capsules significantly reduces the mortality rate (7.1%, P＜0.01) of infection animal.The heavy dose of group of medicine of the present invention significantly reduces the mortality rate (64.3%, P＜0.05) of infection animal.The mortality rate of Chinese medicine contrast GUILONG KECHUANNING JIAONANG infection animal and infected group be no significant difference relatively.

Brief summary

Pathogenic staphylococcus aureus is used in this experiment, with 95% fatal dose lumbar injection infection animal, observes medicine of the present invention to the protective effect of infected mice.The result shows that this medicine heavy dose has significant protective effect to the animal of infection of staphylococcus aureus.

9-3 medicine of the present invention is to the protective effect of charrin's disease mice

Summary with bacillus pyocyaneus with 95% fatal dose to the mouse peritoneal infectable infection after, observe this medicine to the protective effect of infected mice.The result shows that this medicine does not have significant protective effect to the charrin's disease mice.

Purpose is observed this medicine to the protective effect of infection animal with golden bacillus pyocyaneus after to the mouse peritoneal infectable infection.

Material

Medicine is subjected to reagent, Chinese medicine contrast GUILONG KECHUANNING JIAONANG, western medicine group Cefradine Capsules, the compound method of preparation, source, dosage, lot number and medicine ditto test.

Strain is provided by the first clinical hospitals clinical laboratory of Beijing Medical University from the pathogenic bacillus pyocyaneus (J27) of clinical patient separation and Culture.Diluting with 5% gastric Mucin before use being inoculated in the fresh cultured thing of cultivating 18 hours in the M-H culture medium.LD to mice ₉₅Be 10 ^-4.0

94 of animal health ICR mices, male and female half and half, body weight 18～22g is provided by Beijing dimension tonneau China Experimental Animal Center.Licence numbering: SCXK11-00-0008.

Method is divided 6 groups at random with experimental animal, and namely antibacterial infects 24 of matched groups (abbreviation infected group), Western medicine contrast Cefradine Capsules group, Chinese medicine contrast GUILONG KECHUANNING JIAONANG group, big or middle each 14 of small dose group, the male and female half and half of reaching of medicine of the present invention.Antibacterial infects beginning in front 7 days with the volume gastric infusion of 10ml/kg, 1 time on the 1st, continuous 7 days.After the last administration, dyed with 0.6ml/ dosage lumbar injection bacillus pyocyaneus bacterium liquid inductance only respectively in 1 hour, observe day by day animal dead, through x ²The difference between administration group and the infected group is compared in check, and calculates mortality rate.

The result

The results are shown in 16-4.

Table 16-4: medicine of the present invention is to the protective effect of charrin's disease animal

By table 16-4 result as seen, animal because of the infection Post-dead duration all in 48 hours, dead animal continues to observe and 1 week occurred dead again in 48 hours.Infect matched group 91.7% animal dead in 48 hours.The positive control drug Cefradine Capsules significantly reduces the mortality rate (28.6%, P＜0.01) of infection animal.Medicine heavy dose of the present invention has reduced the mortality rate (78.6%) of infection animal, but compares without significant difference (P＞0.05) with the infection matched group.The mortality rate of Chinese medicine contrast GUILONG KECHUANNING JIAONANG group infection animal and infected group be no significant difference relatively.

Brief summary

Pathogenic bacillus pyocyaneus is used in this experiment, with 95% fatal dose lumbar injection infection animal, observes medicine of the present invention to the protective effect of infected mice.The result shows that this medicine does not have significant protective effect to the animal of charrin's disease.

Claims

1. Chinese medicine extract, it is made by the raw material that comprises following Chinese medicine: Herba Ephedrae 100-200 weight portion, Radix Scutellariae 100-200 weight portion, Radix Glycyrrhizae 100-200 weight portion, Oleum Viticis Negundo 0.2-1 weight portion.

2. Traditional Chinese drug mixture, it comprises following active component: liquirtin, Herba Ephedrae total alkali, baicalin and Oleum Viticis Negundo, wherein the weight ratio of liquirtin, Herba Ephedrae total alkali, baicalin and Oleum Viticis Negundo is 2～2.5: 1: 2～2.5: 0.02～0.2.

3. Chinese medicine composition, it comprises Chinese medicine extract claimed in claim 1 or Traditional Chinese drug mixture claimed in claim 2 as effective ingredient and one or more medicinal adjuvants, excipient, diluent or solvent.

4. the preparation method of Chinese medicine extract claimed in claim 1, the method may further comprise the steps:

5. each described Chinese medicine extract of claim 1-3 or Chinese medicine composition be in the purposes of preparation in the medicine, and described medicine has antiinflammatory, analgesic, spasmolytic, relievings asthma, antitussive, eliminate the phlegm, strengthen at least a effect in immunity, antibacterium or the antiviral.

6. each described Chinese medicine extract of claim 1-3 or Chinese medicine composition are in the purposes of preparation in the medicine, described medicine is used for the treatment of and/or prevents at least a in the following inflammation in respiratory system: comprise the inflammation that antibacterial, fungus, virus, mycoplasma, chlamydia, legionella, rickettsia, Pneumocystis carinii etc. cause by the biopathogen body, and the inflammation that causes of the abiotic pathogen factor.

7. purposes claimed in claim 6, it is characterized in that described biopathogen body is antibacterial, described antibacterial is selected from least a in the following antibacterial: staphylococcus aureus, staphylococcus epidermidis, streptococcus, escherichia coli, micrococcus catarrhalis, klebsiella spp, legionella, bacillus pyocyaneus, streptococcus pneumoniae and Bacillus proteus.

8. purposes claimed in claim 6, it is characterized in that described biopathogen body is virus, described virus is selected from least a in following: influenza virus, Coxsackie virus, coronavirus, Measles virus, parainfluenza virus, respiratory syncytial virus, rhinovirus, adenovirus, herpesvirus, cytomegalovirus.

9. each described Chinese medicine extract of claim 1-3 or Chinese medicine composition be in the purposes of preparation in the medicine, and described medicine is used for the treatment of and/or prevents at least a in the following clinical symptoms: cough, heating, dyspnea, spitting of blood, expectoration, out of breath, wheezing, pant, chest pain etc.

10. each described Chinese medicine extract of claim 1-3 or Chinese medicine composition are in the purposes of preparation in the medicine, described medicine is used for the treatment of and/or prevents at least a in the following clinical sign: hyperpyrexia, sweating and not understanding, it is out of breath to cough, and flaring of nares is rough, and it is yellow thick or cough up rusty expectoration to cough up phlegm, chest pain, thirsty agitation, yellowish or reddish urine is hard and dry.Red tongue with yellow fur, slippery and rapid pulse or big vast number.