CN1119157C - Cough and asthma relieving and phlegm eliminating capsule and its preparation - Google Patents

Abstract

The present invention relates to a capsule for relieving cough, eliminating phlegm and relieving asthma, and a preparation method thereof. The capsule is prepared from epimedium herb selenium, licorzinc, toad venom, funnelid physochlaina root, tea leaf and balloonflower root; effective components are extracted by a special preparation technique, the safe using quantity is adjusted, and finally, the capsule is formed. The capsule can predominatingly tonify the kidney to cure respiratory diseases effectively, particularly intractable acute and chronic bronchitis, intractable acute and chronic bronchial asthma, intractable acute and chronic tussis, cor pulmonale, etc. The capsule has the advantages of high efficiency, high safety and specific effect.

Description

Cough-relieving, eliminate the phlegm, Asthma capsule and preparation method thereof

The present invention relates to treat the medicine of respiratory tract disease, especially a kind of cough-relieving, eliminate the phlegm, Asthma capsule.

In the medical domain, respiratory tract disease is a frequently-occurring disease, especially lung cardiovascular diseasess such as intractable acute/chronic bronchitis, intractable acute and chronic bronchitis asthma, the cough of intractable acute and chronic, pulmonary heart disease, the treatment difficulty is very big, common drug can not be eradicated at all fully, the patient gets after being ill, body and mind and misery thereof.

The objective of the invention is to provide a kind of is the main treatment respiratory tract disease with the kidney invigorating, efficient, safety, specially good effect, can effectively solve the patient suffering cough-relieving, eliminate the phlegm, Asthma capsule.

For achieving the above object, the present invention is by the following technical solutions:

A kind of cough-relieving, eliminate the phlegm, Asthma capsule, prescription consists of Herba Epimedii selenium, zinc glycyrrhizate, Venenum Bufonis, Radix Physochlainae, Folium Camelliae sinensis, Radix Platycodonis.

Above-mentioned cough-relieving, eliminate the phlegm, the preparation method of Asthma capsule is that concrete processing step is as follows:

(1) Herba Epimedii selenium extraction process:

(1) crude product Herba Epimedii selenium extraction process: the former medicine of crude product adds 8 times of amount 1% selenic acid liquid, kept 80 ℃ of reflux, extract, 3 hours, the leaching medicinal liquid is put in addition, residue adds 5 times of amount 1% selenic acid liquid again, press the Same Way operation and extracted 2 hours, multiple leaching medicinal liquid and preceding liquid merge, and gather all selenic acid extracting solution, be condensed into than weighing 1.1～1.2, add 95% ethanol equivalent precipitated impurities, left standstill 12～14 hours, extract supernatant liquid filtering, precipitation is with 45% washing with alcohol 2～3 times, the solubility composition washes out in will precipitating, and filtrate and washing liquid merge, and reclaims ethanol, concentrating under reduced pressure is cooled to cream, promptly gets the thick extracted extract of Herba Epimedii selenium;

(2) pure product Herba Epimedii selenium extraction process: the thick extracted extract of Herba Epimedii selenium adds 70%4 times of amount ethanol, and reflux 2 hours is filtered, and filtering residue adds 2 times of amount alcohol refluxs 1 hour again, filters, and reclaims ethanol, and 60 ℃ of dryings promptly get pure product Herba Epimedii selenium;

(3) epimedium brevicornum polysaccharide selenium extraction process: Herba Epimedii is pulverized coarse powder and is added 5 times of amounts of 75% ethanol, 0.5% selenic acid (Ha2SeO4) reflux 2 hours, filter, extract 3 times with method, merging filtrate is condensed into cream, adds 95% ethanol with being stirred to precipitation, 12 hours after-filtration, reclaim ethanol, continuous 2 times, add 2 times of amounts of water, with DEAE cellulose (phosphate type) column chromatography purification, get pure product epimedium brevicornum polysaccharide selenium;

(2) zinc glycyrrhizate extraction process:

(1) thick zinc glycyrrhizate extraction process: thick Radix Glycyrrhizae powder is measured 0.5% zinc carbonate (ZnCO3) seepages with 12 times, and continuous 3 times, effusion is concentrated into original volume 1/5 and filters, filtrate adds concentrated sulphuric acid to PH3, filters the precipitation of separating out, and washes 3 times, dry below 60 ℃, promptly get thick zinc glycyrrhizate;

(2) pure product zinc glycyrrhizate extraction process: above gained zinc glycyrrhizate 400g adds 4 times of amount ethanol, reflux 3 hours, filter, filtering residue adds 2 times of amount alcohol heating reflux 2 times, merges all backflow and adds the 10g active carbon, reflux decolour cooling half an hour, filter, filtrate adds ZnCO3 to PH7～7.5, till no solid is separated out, the filtrate precipitation, with the small amount of ethanol washing, drying at room temperature gets zinc glycyrrhizate 250g;

(3) glycyrrhiza residue and precipitate extract zinc glycyrrhizate, glycyrrhizic acid calcium, licoflavone: Radix Glycyrrhizae residue and precipitate add 1% zinc sulfate (ZnSO4) and 70% ethanol is lyase, hot dipping 8 hours, reflux 2 hours, filter, continuous 2 times, merging filtrate reclaims ethanol, be condensed into cream, promptly reclaim zinc glycyrrhizate, glycyrrhizic acid calcium, licoflavone;

(3) Venenum Bufonis extraction process:

(1) Venenum Bufonis concocting method: Venenum Bufonis was advisable with 60% soak with ethanol in 24 hours, Venenum Bufonis is no change before and after steeping in wine system, but total cardenolide content content after steeping in wine system has improved, think and not only help after the steeping in wine system pulverizing, and enhancing drug effect, and toxicity reduces 30～50%, and mice LD50 is 403.7～540.8mg/kg after the steeping in wine system;

(2) Venenum Bufonis is ground into 14～40 mesh sieve powder, adds 95% alcohol heating reflux 3.75 hours;

(4) Radix Physochlainae is extracted Rhizoma Scopoliae Japonicae, Anisodamine extraction process: get Radix Physochlainae 1000g, press seepage method seepage with 70% ethanol, collect effusion 10000ml, reclaim ethanol and be concentrated into 500ml, put separatory funnel defat with petroleum ether 2 times, divide water intaking liquid, steam and remove unrecovered oil ether, add strong aqua ammonia and regulate PH10～11, gradation 250ml, 200ml, the 150ml chloroform is carried most alkaloid, combined chloroform liquid, gradation is with 2% hydrochloric acid 200ml and 1% hydrochloric acid 300ml, 200ml, 100ml carries most alkaloid, merge sour extract, add strong aqua ammonia and transfer PH10～11, gradation chloroform 300ml, 200ml, 100ml carries most alkaloid, combined chloroform liquid, use 1% hydrochloric acid 200ml and 0.5% hydrochloric acid 200ml respectively, 100ml carries most alkaloid, merge sour extract, transfer PH2～3, heating in water bath, remove residual chloroform, add 0.2% decolorizing with activated carbon, filter, be condensed into crystallization;

(5) Folium Camelliae sinensis extracts caffeine technology: Folium Camelliae sinensis adds 8 times of amount 1% sulphuric acid liquid and soaks seepage after 14 hours, continuous 3 times, merging filtrate is concentrated into original volume 1/5 and filters, and filtrate transfers to PH7 with ammonium hydroxide (NH4OH), add 95% ethanol equivalent precipitated impurities, left standstill 12 hours, and extracted supernatant liquid filtering out, precipitation is with 45% washing with alcohol 2～3 times, be condensed into cream, promptly get theophylline and caffeine crystallization;

(6) Radix Platycodonis extract technology: get Radix Platycodonis,, add 8 times of amounts of 55% ethanol and make solvent by the seepage method, flooded 48 hours, with per minute 1～3ml speed seepage, spill fully to institute's soluble components, collect and continue seepage, continuous 3 times, merging filtrate filters, to below 60 ℃, cryoconcentration is dried to extractum to the thick paste shape;

(7) capsular preparation process:

Select each composition safety using amount to be: Herba Epimedii selenium 50mg/kg/ day; Epimedium flavone 20mg/kg/ day; Epimedium brevicornum polysaccharide selenium 20mg/kg/ day; Radix Glycyrrhizae extract zinc glycyrrhizate 20mg/kg/ day; Venenum Bufonis 0.32mg/kg/ day; Radix Physochlainae extract scopolamine 0.012mg/kg/ day, Anisodamine 0.3mg/kg/ day; Folium Camelliae sinensis extract theophylline 8mg/kg/ day, caffeine 4mg/kg/ day; Radix Platycodonis extract kikyosaponin 50mg/kg/ day amounts to 8622.1mg/50kg/ day, is divided into 18 large size capsules, and each capsule contains 479mg.

Below introduce the effect that the present invention has by pharmacology, the drug effect of each composition:

One, cough-relieving, eliminate the phlegm, the medicine characteristics of Asthma capsule:

1. we have novelty, reasonable recipe.Have efficient, low toxicity, the minimum characteristics of side effect, be the kidney invigorating, antitussive, reduce phlegm, anti-asthmatic.Be made up of Herba Epimedii, Radix Glycyrrhizae, Venenum Bufonis, Radix Physochlainae, Folium Camelliae sinensis, Radix Platycodonis, clinical cure rate, obvious effective rate, improvement rate, effective percentage are very high, and toxic and side effects is very little.Efficiently: 1. treat cough (acute and chronic bronchitis) 466 examples, cure 416 examples, cure rate 89.27%, total effective rate 98.93%.2. dispelling the wind and dampness pathogens pyretic pulmonary disease (acute pneumonia pathological changes) 280 examples are cured 251 examples, cure rate 89.61%, total effective rate 98.57%.3. disease (blocking emphysema, pulmonary heart disease, pulmonary insufficiency) 187 examples are breathed heavily in treatment, cure 125 examples, cure rate 66.83%; Total effective rate 97.86%.4. treat bronchial wheezing (bronchial asthma, asthmatic bronchitis) 218 examples, cure 145 examples, cure rate 66.51%, total effective rate 98.17%.5. (coughing) blood (bronchiectasis) 51 examples are coughed up in treatment, cure 35 examples, cure rate 68.63%, total effective rate 96.08%.(annotate: the diagnosis criterion of therapeutical effect, by State Administration of Traditional Chinese Medicine's issue, traditional Chinese medical science disease diagnosis criterion of therapeutical effect is implemented on January nineteen ninety-five 1.All merging severe bacterial infections persons, part patient add with antibiotics and liquid supporting treatment).Quick-acting: cough in 1～2 hour obviously alleviated after most patients took medicine, and sputum reduces, and pants and calms down.Low toxicity: have 1% left and right sides patient that gastrointestinal reaction or dizziness are arranged after taking medicine, 0.2% patient has anaphylaxis.

2. be somebody's turn to do the strong expansion bronchus smooth muscle in side, eliminate the edema that bronchial mucosa causes because of inflammation, eliminate airway resistance, help expectoration.And antibiotic, antivirus action arranged.

3. this side has the breathing excitation, strengthens respiratory muscle function, helps harmful dirty gas discharges such as carbon dioxide, increases the oxygen suction volume, promotes gas exchange, control cardiopulmonary and important organ pipe anoxia, acidosis.

4. this medicine has very strong resolve phlegm effect, helps expectorant and discharges, and eliminates airway resistance.

5. this medicine has very strong bronchiectatic activity, and strong antihistaminic, antiinflammatory action are arranged again, the tunica mucosa tracheae protective effect, and control is relievingd asthma because of inflammation allergy etc. causes that the bronchial mucosa edema reaches.

6. the strong expansion artery and vein of this medicine blood vessel reduces the forward and backward load of heart, strengthens myocardial contraction, and decreased heart rate is adjusted the rhythm of the heart, strengthens the diuresis effect, reduces the cardiopulmonary oxygen consumption, control intractable heart failure.So disease (pulmonary heart disease, obstructive emphysema, pulmonary insufficiency) is breathed heavily in treatment effect unique is arranged.

7. blood viscosity lowering is removed platelet aggregation, and antithrombotic forms and the thrombus dissolving effect, the control heart, brain, lung infraction.

8. this medicine can be kept the heart, brain, pneumonocyte film, DNA mitochondrial DNA film, lysosome membrane, Golgi body membrane permeability function, stablize the heart, brain, lung, nephrocyte system integrity, postponing irreversible damage takes place, pretend very much usefulness at protein synthesis with promoting to rise in the heart, the pneumonocyte repair process, and quicken the reparation of the heart, brain, lung, bronchus blood vessel infarct cell, prolong the heart, brain, ischemia of lung anoxia time-to-live and heart and independently beat the time, the control heart, brain, lung infraction back cell are repaired as early as possible as early as possible.

9. this medicine blood fat reducing, prevent and treat arteriosclerosis, blood pressure lowering, inhibition and cause the heart, the large and small arterial inflammation of lung blood vessel and blood vessel inflammation damnification because of inflammation, immunodeficiency and immunoreation, the bronchus inner membrance all has strong repair because of inflammation damnification etc.10. this medicine has strong the kidney invigorating effect, and energy immune stimulatory globulin and antibody produce, and can induce r-globulin and interleukin II and produce.Immunity there is dual regulation, removes free radical and peroxidation, strengthen the health resistance against diseases, make the heart, brain, each vitals of lung avoid infringement, prolong life, life lengthening.

Two, cough-relieving, reduce phlegm, the pharmacological action of Asthma capsule:

The pharmacological action of Herba Epimedii

(1) antitussive, eliminate the phlegm, relieving asthma: prove that with the phenol red excretion method of mice the aquatic foods product crude extract of Herba Epimedii and the ethyl acetate extract of dry product have certain phlegm-dispelling functions.Drawing the method for coughing with mice sulfur dioxide proves, methanol and ethyl acetate extract have antitussive effect; Methanolic extract can also suppress to stimulate the cough due to the cat superior laryngeal nerve.Antitussive is central.Methanolic extract has protective effect to drug-induced asthma.

(2) coronary artery dilator: the Herba Epimedii decoct can increase the coronary flow of guinea pig isolated heart.The non-amino acid moiety that extracts in its aqueous extract sheet can increase the coronary flow of the extrasomatic rabbit heart and the anesthetized dog heart, reduces the coronary resistance of the dog heart, to not obviously influence of heart rate; The Acute Myocardial Ischemia in Rats that pituitrin is caused has protective effect, and can shorten epinephrine or the caused experimental arrhythmia of strophantin K significantly.

(3) blood pressure lowering: pure preserved material and methanolic extract, anesthetized rabbit have obvious and persistent hypotensive activity, and methanolic extract is given normal and the hypertensive rats gavaged of kidney type, tangible blood pressure drops also occurs; Give the cat lumbar injection, can make the blood pressure of a part of cat that reduction is to some extent arranged.Because it can weaken pressor reflex significantly and the effect of expansion rabbit ear blood vessel is arranged, its hypotensive effect may be direct blood vessel dilating and the dual reason that suppresses vasomotor center.(4) androgen sample effect: give injected in mice Herba Epimedii preparation, can make the important increase of prostate, seminal vesicle and levator ani, prove the effect of androgen sample, render a service than a little less than the Fructus Cnidii, strong than Gecko and Hippocampus.Can promote the excretory effect of dog sperm; The strongest with leaf and the effect of root preparation, behind the application Herba Epimedii, the excretion of 17-KS also obviously increases in the urine, illustrates having certain effect aspect the promotion gonad function.

(5) antibiotic and antiviral: white and staphylococcus aureus, streptococcus pneumoniae, Nai Shi micrococcus catarrhalis, hemophilus influenza, tubercule bacillus are had inhibitory action.Poliovirus and some enterovirus have inhibitory action.

(6) antiinflammatory: methanolic extract can alleviate the swelling degree of rat Ovum Gallus domesticus album " arthritis " significantly.Reduce the phenomenon that the thin vascular permeability of the rabbit hair due to the histamine increases, can increase the phagocytic activity of mice inflammatory exudation cell.Increase mice and under normal pressure, tolerate anoxybiotic ability.The extracting solution of Herba Epimedii can also make the blood glucose of experimental hyperglycemia rat obviously reduce.

(7) pharmacokinetics: trace manganese is in the dynamic (dynamical) research of generation of Sanguis Leporis seu oryctolagi Chinese medicine in the Herba Epimedii, with the Catalytic-Kinetic Analysis is monitoring means, utilize the catalytic action of divalent manganesetion to Potassium metaperiodate .-rhodamine B reaction system, use Phen to be activator, trace manganese in the Sanguis Leporis seu oryctolagi has been carried out fluoremetry, curve when having drawn medicine, the result is through MICROCOMPUTER PROCESSING, physiological disposition meets two Room open models, and has obtained serial pharmacokinetic parameter.

(8) toxic and side effects: the LD50 of Herba Epimedii extractum mouse peritoneal injection is 36g/kg.The LD50 of the quiet notes of non-amino acid moiety (No5-1-1) mice that extract in the aqueous extract sheet is 56.8 ± 2.7g/kg.The toxicity of methanolic extract is low, and mouse gavaging 450g/kg observed 3 days continuously, and activity as a result is normal, non-toxic reaction.

The acute toxicity test of mouse peritoneal injection Herba Epimedii total flavones, LD50 is 2.99 ± 0.14g/kg.Acute and sub-acute toxicity test shows that Herba Epimedii extracting solution various dose is taken continuously, animal liver, kidney, the heart, spleen etc. is organized all not have obviously change, and mode of appearance is normal.

Mouse peritoneal injection various dose total flavones is observed each dosage treated animal per cent death loss in 24 hours, and trying to achieve total flavones LD50 with the improvement karber's method is 2.99 ± 0.14g/kg.

The mutagenicity study of epimedium brevicornum polysaccharide, the inside and outside every mutagenicity test of effective aspect shows, does not see that EPS has mutagenicity.The pharmacological action of Radix Glycyrrhizae

(1) antitussive: after Radix Glycyrrhizae is oral, can cover on the pharyngeal mucosa of inflammation, reduce the sensitivity that stimulates and antitussive.18-β enoxolone derivative has tangible antitussive effect to Cavia porcellus, and intensity is similar to codeine.This type of preparation all has significant effect, so think the central antitussive effect to chemical irritation and the cough that causes with electricity irritation cat superior laryngeal nerve.Also has phlegm-dispelling functions in addition.

(2) adrenocortical hormone sample effect: the effect of (1) mineralocorticoid sample: Radix Glycyrrhizae extractum, Radix Glycyrrhizae powder, glycyrrhizin, enoxolone all have the effect of desoxycortone sample, the urine amount of kinds of experiments animal and the discharge of sodium are reduced, potassium is discharged to be increased, blood sodium rises, blood calcium reduces, the atrophy of adrenal cortex glomerular zone.If excision both sides adrenal gland, Radix Glycyrrhizae just can not be kept electrolyte balance, can not prolong life.(2) glucocorticoid sample effect: the effect that can significantly strengthen and prolong cortisone.Clinical and zoopery proves that Radix Glycyrrhizae and effective ingredient thereof can make the release 17-hydorxycorticosteroids in urine middle reaches drain and increase, and conjunction type reduces, and can also suppress hypophysis release melanocyte-stimulating hormone.Some preparation that experimental results show that Radix Glycyrrhizae makes the atrophy of thymus gland of rat, and ascorbic content descends in the adrenal gland, and adrenal gland's weight increases, and cortex zona fasciculata amplitude is widened, and blood lymphocyte, eosinophil leucocyte reduce.

Produce adrenocortical hormone sample action principle three kinds of hypothesis are arranged: 1. glycyrrhizin suppresses adrenocortical hormone metabolism inactivation in liver; 2. the electrolyte effect of adrenal cortex reinforcing hormone; 3. only in the presence of a small amount of adrenocortical hormone, the effect of glycyrrhizin competence exertion.

(3) antiinflammatory and antiallergic action: enoxolone is swollen to rat granuloma, the formaldehyde edema, and tuberculin reaction, subcutaneous granulation capsule inflammation has certain inhibitory action.The phase of oozing out and the proliferative phase of ammonium glycyrrhizinate, the subcutaneous granulation capsule of Monosodium glycyrrhetin energy effective influence inflammation, action intensity is weaker than cortisone.Glycyrrhizic acid can suppress the caused guinea pig skin reaction of Ovum Gallus domesticus album significantly, alleviates the symptom of anaphylactic shock.Can suppress the influence of histamine to vascular permeability.Antiinflammatory, antiallergic action principle may be relevant with the inhibition capillary permeability; It has influenced biological oxidation process in the cell, has reduced the reactivity of cell to stimulating.

(4) to the effect of digestive system: experimental ulcer has the obvious suppression effect, can the gastric acid inhibitory secretion, can adsorb gastric acid after oral, and reduce Both of gastric acidity stomach function regulating protease activities.

The liquorice beverage extract increases the hexosamine composition of gastric mucosal cell, and gastric mucosa is without prejudice.The double sodium salt of derivant 18 β of glycyrrhizin-enoxolone hemisuccinic acid ester has antiulcer action.FM100 (not containing glycyrrhizin) can secrete by gastric acid inhibitory, reduces Both of gastric acidity, promotes ulcer healing, can urge the plain effect of gastric secretion by antagonism for rats by intraperitoneal injection, reduces pepsic activity.Glycyrrhizic acid can improve the effect of pylorus mucosa medium ring-adenosine phosphate, suppresses the release of gastrin, may be to due to the inhibition of phosphodiesterase by glycyrrhizic acid.Radix Glycyrrhizae decoct, fluid extract not only have inhibitory action to the animal intestine in vitro, and the intestinal tube spasm that acetylcholine, barium chloride, histamine etc. are caused also has inhibitory action.

(5) detoxifcation: Radix Glycyrrhizae decoct, glycyrrhizic acid can reduce toxicity such as strychnine, histamine, chloral hydrate, urethane, benzene, arsenic, snake venom, diphtheria toxin, diphtherotoxin, tetanus toxin significantly.Heavy dose makes the rat transaminase near normal, and body weight slightly alleviates, and can prolong the time-to-live.

Radix Glycyrrhizae antidotal principle, the someone thinks Radix Glycyrrhizae precipitation alkaloid, and the sorption of medicinal charcoal sample is arranged, and combines with the poisoning medicine at gastric and produces Detoxication.

(6) to the influence of lipid metabolism: behind most of hypertension human glycyrrhizic acids, serum cholesterol and triglyceride descend, the also corresponding reduction of blood pressure.The rabbit of experimental atherosclerosis can prevent the development of large artery trunks and crown arteriopathy kitchen range with low dose of glycyrrhizin, share with estrogen this effect is strengthened.

(7) protect the liver: Radix Glycyrrhizae can alleviate rat liver degeneration and the necrosis that carbon tetrachloride causes significantly, makes the liver glycogen and the most of recovery of rna content or approaching normal of accumulating in the hepatocyte.

(8) analgesia, convulsion: FM100 has significant analgesia role, with the paeoniflorin compatibility synergism is arranged.

(9) other: Radix Glycyrrhizae and glycyrrhizic acid can suppress tulase growth, can strengthen berberine and suppress 1 times of staphylococcus aureus ability, increase bile secretion and urorhodin and drain; Analgesic and anticancer and spasmolysis are arranged, and the anti-AIDS toxic action reaches 98%.

(10) pharmacokinetics: the 1. pharmacokinetic of zinc glycyrrhizate: the absorption of (1) zinc glycyrrhizate: the 1. oral absorption of zinc glycyrrhizate: zinc glycyrrhizate, glycyrrhizin (glycyrrhizic acid), through the oral 100mg zinc glycyrrhizate of normal person, show with enzyme immunoassay mensuration, enoxolone concentration two peaks occur in administration in the blood after 1～4 hour and 10～24 hours, and peak value is about 500mg/ml.2. the absorption of the quiet notes administration of glycyrrhizic acid: 50, the ammonium glycyrrhizinate of 20mg/kg is used the HPLC method and is measured blood sample, and ammonium glycyrrhizinate concentration in blood plasma descended rapidly in 30 minutes, then maintained slow Reduction Level in 60 minutes later on.Enoxolone appears in normal person and the quiet notes ammonium glycyrrhizinate of hepatic injury patient 80mg in blood after 6 hours, peaking after 24 hours is about 7mg/ml hepatic injury patient and is lower than this level.

After no matter being the oral zinc glycyrrhizate of rat or normal person, the concentration of enoxolone is all more than the intravenous injection height in the blood plasma.Zinc glycyrrhizate has been the medicine of important enterohepatic circulation, and its mechanism is because zinc glycyrrhizate is hydrophilic macromole (molecular weight＞820), is not easy at the small intestinal position to absorb, and only minute quantity enters blood by active transport.So after oral, do not detect blood drug level in the short time.Greatly part zinc glycyrrhizate β-glycoside bond on its molecule when small intestinal stops is hydrolyzed into secondary glycoside by the hydrolytic enzyme GRD beta-glucuronidase of intestinal flora, simultaneously the polarity of corresponding reduction zinc glycyrrhizate.The sweet key of a-type sugar on the secondary glycoside becomes β-type by the Walden transposition, continues to be hydrolyzed into enoxolone.This process need certain hour is generally 2～4 hours (rat was finished) in 30 minutes.Enoxolone again can be under the effect of intestinal flora, dehydrogenation on the 3-position, and transposition becomes 3-table enoxolone (3-epi-GA).3. the medicine of zinc glycyrrhizate is for moving the educational level parameter: the pharmacokinetic parameters of zinc glycyrrhizate gives rat 100mg/kg ammonium glycyrrhizinate through vena femoralis injection, shows that with the HPLC measurement result ammonium glycyrrhizinate blood drug level is the two-phase exponential damping, meets opening two-compartment model.Pharmacokinetic parameters average: a=0.42 ± 0.05 minute-1; β * 102=1.34 ± 0.11 minute-1; T1/2 β=54.31 ± 4.85 minute; K12=0.24 minute-1; K21=0.88 minute-1; K10=0.64 minute-1; Vd β (ml)=29.44 ± 0.91.4. the glycyrrhizic acid metabolic enzyme is in the intravital distribution of rat: the main component glycyrrhizic acid (GL) of Radix Glycyrrhizae can change because of the effect generation metabolism of intestinal bacteria.Inquired into the distribution of the pH value and the glycyrrhizic acid metabolic enzyme in the intestinal bacterium flora of rat alimentary canal content.Eat the pH value of the gastrointestinal contents after back 2 hours, stomach is 3～4, intestinal is about 7, and only from caecum and big intestinal contents, detect the metabolic enzyme activity of 3 kinds of glycyrrhizic acids, the antibacterial of rat stomach enteral, have the enoxolone that glycyrrhizic acid is hydrolyzed into glycoside unit, and finally be metabolized to the transfer capability of enoxolone (GA) oxidase active of 3 table bodies through 3 ketoboidies.5. the metabolism after the zinc glycyrrhizate administration.6. Radix Paeoniae and Radix Glycyrrhizae compatibility are to the metabolic influence of enoxolone.2. the pharmacokinetic of licoflavone: licoflavone metabolism in rat bile is a glycyrrhizin.

(11) toxic and side effects: 1. acute toxicity: the acute toxicity of (1) liquorice beverage decoct: the 1. acute toxicity of liquorice beverage decoct: the toxicity of Radix Glycyrrhizae own is very low, and administration treated animal weight ratio matched group slightly increases as a result, but edema do not occur; Experimental session does not have death, and dirty weight check only adrenal gland's weight has reduction slightly, due to the adrenocortical hormone sample effect of Radix Glycyrrhizae after the administration.2. the acute toxicity of liquorice beverage extractum: liquorice beverage extractum mice LD50 intravenous injection is 1.9432 ± 0.467g/kg, and lumbar injection is 6.8466g/kg, and subcutaneous injection is 7.8192g/kg.The LD100 of Radix Glycyrrhizae extractum mouse subcutaneous injection is 3.6g/kg, and the cause of the death is a respiratory paralysis.(2) acute toxicity of effective liquorice: the MLD of glycyrrhizin mouse subcutaneous injection is 1g/kg, and the LD50 of enoxolone mouse peritoneal injection is 308mg/kg, and dead animal is seen the peritoneum inflammation, injects medicine and does not absorb fully.The LD50 of Carbenoxolone Sodium acid half ester mouse peritoneal injection is 101mg/kg, during quiet notes is 43mg/kg, Radix Glycyrrhizae methanolic extract Fm100 mouse peritoneal injection LD50 is 760mg/kg, and enoxolone can suppress the Cavia porcellus thyroid function, and the trend that reduces basal metabolism is arranged.2. long term toxicity: Radix Glycyrrhizae extractum 1g every day gavages 40 days to rabbit, and administration group as a result slightly increases than matched group body weight, and in a week after the administration, sodium content obviously rises in the blood, one week the back more constant, adrenal gland's underactivity, and atrophy is arranged slightly.Radix Glycyrrhizae extractum is given and to be gavaged in continuous 6 weeks of Cavia porcellus 2g/kg every day, and result and matched group comparison body weight have increase (but non-edema causes) slightly, does not have deadly in the experiment, checks that each organ weights sees that adrenal gland's weight reduces, and the rarely seen glomerule of tissue examination is some unusually.The injection down of Carbenoxolone Sodium acid half ester 500mg/kg cat skin, rabbit 2.5mg/kg subcutaneous injection, all logotype is 30 days, and the body weight no change does not have dead yet.Glycyrrhizin heavy dose (20～30mg/kg is more than the continuous week) can cause edema, but can disappear after the drug withdrawal.Heavy dose of enoxolone 125mg/kg suppresses mouse breathing, weight loss, and enoxolone can suppress the Cavia porcellus thyroid function, and the trend that reduces basal metabolism is arranged.3. specific toxicity: adopt the rec-assay method to carry out mutagenesis testing, find that 40 ℃ of cold extraction things of Radix Glycyrrhizae are positive, 90 ℃ of heat extraction substrates are negative.

The pharmacological action of Venenum Bufonis

(1) excited respiratory center: breathing and central nervous system are had excitation.Bufogenin (Resibufogenin) is thought a kind of analeptic of breath cycle preferably.After the injection, making in adult's ventilation one minute increases about 2.1 liters, keeps 20 minutes, and drug effect can be better than lobeline, nikethamide.The respiration inhibition that causes for the commonly used adjuvant of middle fiber crops such as barbiturates, dolantin etc. has significant antagonism; To chlorpromazine, dolantin and caused hypotension of hibernation, pressor effect is arranged also.Boosting there is no the too high phenomenon of increased blood pressure rapidly, lastingly.(2) heart tonifying diuresis: Venenum Bufonis and bufadienolide thereof have the cardiotonic of similar Folium Digitalis Purpureae, can be directly excited myocardium, and shrink and strengthen.Heart tonifying strengthens myocardial contraction, improves circulation, and hydrouria is eliminated cardiac edema.Suppress the heavily absorption of Na+, the natriuretic diuretic effect at renal tubules.

(3) antiinflammatory: the permeability that suppresses blood vessel wall.

(4) local anesthesia: Venenum Bufonis solution and effective ingredient bufalin, cinobufagin etc., be used for around the tip of the tongue, lip, the oral cavity, feeling of numbness is arranged, can keep 90 minutes approximately.Bufalin is bigger tens of times than cocaine to the local anesthesia effect of rabbit corneal, and is bigger hundreds of times than procaine, and acting duration is long, and local anesthetic action mainly is optionally to act on sensory nerve ending.

(5) antitumor: isolated toadpoison lactone from animal has the effect that suppresses tumor.About its antitumor action principle, be to suppress due to nucleic acid synthetic.

(6) pharmacokinetics: the 1. oral pharmacokinetics of Venenum Bufonis: the oral easy absorption of Venenum Bufonis, effect take place and disappear all fast, no cumulative action.Discovery is higher with liver, intestinal concentration, is stomach, the heart, kidney, brain, muscle secondly.Plasma half-life is short, only 7.5 minutes.Urinary volume less (account for injection rate 4.4% and 1.93%) in 24 hours, each tissue content is the highest with the heart, is spleen, brain, lung, liver, kidney secondly.Mainly discharge from kidney, it is the highest to inject in back 8 hours kidneys content, has almost all arranged after 24 hours.2. Venenum Bufonis and strophantin K are to Cor Canitis muscular strength effect relatively: Venenum Bufonis and strophantin K relatively by (dp/dt)/p, dp/dtmax, Vmax, left ventricular pressure and aorta flow, have carried out the comparative observation of Venenum Bufonis preparation and strophantin K to Cor Canitis muscular strength effect to 12 anesthesia Canis familiaris L.s.The result shows, two kinds of medicines promote the contractility degree and action time process similar substantially.Administration is early stage, and the parameters climbing obviously improves than malicious K in the Venenum Bufonis group, and wherein left constant pressure and dp/dtmax change the most very.The experimental result prompting, Venenum Bufonis has dual positive inotropic action to cardiac muscle.Each index administration previous crops is a control level, show for behind Venenum Bufonis and the malicious K 30 seconds, 1,2,3,5,15,30,60 minute the average rate of change and standard error scope measurement result, give behind the Venenum Bufonis in early days, each parameter has in various degree and rises, compare with malicious K, significant difference (P＜0.05) was arranged in the time of 30 seconds.After the administration 1 minute, LVP, dp/dt, cardiac output still reached statistics difference (P＜0.05).Index begins to descend subsequently, and near malicious K change level (P＞0.05).In the time of 3 minutes, the Venenum Bufonis effect makes (dp/dt)/p and Vmax greatly progressively increase once again, and is similar to malicious K variation beginning.Two medicines all peaked in the time of 15 minutes, progressively reduced again later on.In a word, Venenum Bufonis can produce the effect of a quick similar epinephrine effect, the positivity effect that can produce a similar heart tonifying glycoside again simultaneously.

(7) toxic and side effects: 1. acute toxicity: rapid breathing, muscle spasm, convulsions, not agent of the rhythm of the heart appear in mice behind quiet notes or the lumbar injection Venenum Bufonis, at last paralysis and dead.Venenum Bufonis and composition thereof are to the LD50 (mg/kg) of mice, and acute toxicity test LD50 is 60.7mg/kg.Be that Venenum Bufonis is 41.0 (quiet notes), 96.6 (subcutaneous), 36.24 (abdominal cavities), Toadpoison Medicine is 2.2 (abdominal cavities), and cinobufagin is 4.38 (abdominal cavities), and inviting this bufotalin is 4.25 (quiet notes), and bufotoxin is 0.36 (quiet notes) to Canis familiaris L. LD50, oral 0.98.2. subacute toxicity: 40 of laboratory animal mices, male and female dual-purpose, body weight 19～24g, divide 4 groups at random, every group 10, divide basic, normal, high dosage group (to be respectively 10mg/kg, 25mg/kg, 50mg/kg) and matched group (only) with Sterile Saline 0.5ml/, equal lumbar injection, once a day, totally 15 days, each treated animal outward appearance during administration is active, and appetite and defecation are no abnormal.Hemoglobin, leukocyte and the lymphocyte value of each group only have slight fluctuations before and after the experiment, and difference is remarkable (P＞0.05) not.Routine urianlysis is no abnormal.But body weight is respectively 23.3 ± 1.4g, 21.7 ± 1.2g, 22.1 ± 1.7g, 22.5 ± 1.4g before experiment; Be respectively 27.7 ± 1.9g, 23.9 ± 3.0g, 26.8 ± 2.3g, 27.0 ± 2.4g after the experiment.Each is organized and self compares t=2.19～6.00, P＜0.05～0.01, and weight increase is remarkable.It is hemorrhage that cardiac muscle once appearred in Cutis Bufonis preparation animal experiment, and can cause Columba livia, dog vomiting, and atropine has certain Detoxication to this, and epinephrine is then invalid.Bufo siccus subtracts greatly through boiling toxicity.Administration expired back 1 day, all put to death and dissected, and each internal organs of each treated animal of perusal show no obvious abnormalities, and tissue slice microscopies such as the heart, lung, liver,spleen,kidney, brain and epinephrine are not also seen any pathological changes.

The pharmacological action of Radix Physochlainae

Contained atropine Alkaloid of Radix Physochlainae root and derivant thereof, alkaloids such as hyoscyamine, scopolamine are about 0.26%, and these two kinds of alkaloids are treatment bronchitis effective ingredient, and can resist the tachycardia that Venenum Bufonis causes.Respiratory center there is excitation, but cerebral cortex is had obvious inhibitory action, expand blood capillary in addition, improve the dimension Circulation.

(1) phlegm-dispelling functions of relievining asthma: Radix Physochlainae has tangible relieving cough and expelling phlegm antiasthmatic effect, chloroform extraction alkaloid and ether extract alkaloid and oil, strong eliminating phlegm and relieving asthma effect is arranged, can be used for coughing phlegm dyspnea, palpitation and insomnia respiratory failure has good curative effect, this product is to breathing excitement, brain is sedation, shaking palsy, mad dry property psychosis and encephalitis b respiratory failure, pulmonary heart disease respiratory and circulatory failure, obstructive emphysema are had good effect.Particularly Anisodamine has good effect to brain, the heart, pulmonary infarction, paralysis, the heart, brain, lung vasospasm obturation, can rescue shock.

(2) tranquillizing and allaying excitement: Radix Physochlainae decoct lumbar injection or filling stomach, the laboratory animal activity is reduced, still respond but stimulate to external world.And can resist the excitation that caffeine sodium benzoate, amfetamine cause mice.

(3) blood pressure lowering: zoopery proves that the initial stage of taking medicine, visible blood pressure edged down, microlitre again later on, and then continue to descend, heart also there is certain inhibitory action.

(4) suppress smooth muscle: tentatively think to directly act on smooth muscle, the smooth muscle of tense situation is alleviated.Heavy dose can make the intestinal smooth muscle paralysis.The pregnant autorhythmicity at the body rabbit uterus is shunk to be reduced and weakens.

(5) toxic and side effects: mouse peritoneal injection decoct LD50 is 43g/kg.Because of it contains the atropine Alkaloid, clinical practice mainly contains xerostomia, dizziness, blurred vision, platycoria, blood pressure reduction; But hypertension person is also arranged, and individual patient has urine retention.The careful usefulness of glaucoma patient.

Consumption: the oral 0.2～0.6mg of Rhizoma Scopoliae Japonicae consumption, 0.6～1mg on the 1st; Maximum dose 0.6mg, day 2mg; Anisodamine 5～10mg, 2 times/day, rescue shock 10～40mg.i.v controls the quiet notes of cerebral thrombosis 30～40mg+5%GS500ml.

The pharmacological action of Folium Camelliae sinensis

(1) respiratory system: the contained theophylline of Folium Camelliae sinensis, caffeine, the Ke Ke alkali bronchial smooth muscle that can relax, effect is more obvious when bronchial smooth muscle is in spasticity, because theophylline can suppress PDE, the hydrolysis rate of Cyclic Adenosine monophosphate slows down, and increase its concentration in tissue, impel bronchial smooth muscle lax.The energy coronary artery dilator, but oxygen consumption increases simultaneously, and the existence of ethylene diamine can make bronchus effect loose and coronary dilation strengthen in the molecule.Theophylline can also reduce renal tubules to electrolytical heavy absorption, increases glomerular filtration rate and diuresis is arranged.Can treat bronchial asthma, cardiac edema, cardiac asthma etc.

(2) blood circulation: caffeine, theophylline directly act on heart, owing to can suppress the phosphodiesterase in the heart, thus the concentration of ring phosphorus one adenosine monophosphate (cAMP) is increased, thereby make cardiac muscle excited, mental and physical efforts occurring and strengthen, heart rate is accelerated.

To the effect of blood vessel, maincenter and tip double properties are arranged; Because can excited vasomotor center, thereby internal organs and cerebral vessels be shunk; But because direct blood vessel dilating smooth muscle still, and make skin, arteria coronaria, kidney vasodilation, so can be used for some hypertension.On the intensity of vasodilation and cardiotonic, theophylline is the most remarkable, and Ke Ke alkali takes second place, and caffeine is the most weak.

(3) diuresis: the caffeine class has significant diuresis, and its action intensity weakens successively by theophylline, caffeine, Ke Ke alkali.

(4) central nervous system: Folium Camelliae sinensis and effective ingredient caffeine thereof have tangible excited central action, at first are cerebral cortex, and along with the increase of dosage, excited in succession oblongata influences spinal cord at last.

Caffeine is to the selective excitation of cerebral cortex, thus can eliminate sleepy, cheer up, lessen fatigue, and improve thinking activities.The active oral dose of the general excited cerebral cortex of caffeine (0.2～0.3g) does not influence normal bulbar center, only when subcutaneous injection heavy dose of (0.5g), and can excited respiratory center, vasomotor center and vagus nerve maincenter.When these maincenters were suppressed (anesthetics, infectious disease), caffeine then appreciable stimulating action can occur, thereby made exaggerated respiration, quickening, increased blood pressure, and heart rate is slightly slow in short-term, changes quickening very soon into.

(5) cholesterol reducing and fibrinolysis: tea tannin and Citrin, vitamin C, can alleviate atherosclerosis, reduce serum cholesterol, the ratio of cholesterol reducing and phosphide prevents that neutral fat from depositing in blood, liver.Impel Fibrinogen to be cracked into FDP rapidly and influence coagulation function, activate fibrinolysin unit-Wei lyase system, similar to the effect of urokinase.This anticoagulation aspect treatment coronary heart disease and atherosclerosis, is paid attention to for people.

(6) antibiotic: the Folium Camelliae sinensis decoct is the strongest to staphylococcus aureus and bacterium flexneri effect; Secondly be bacillus pyocyaneus, Bacillus typhi; And the sensitivity of escherichia coli, streptococcus and pneumobacillus is relatively poor.Also be used for urinary system infection, respiratory tract infection and suppurative wound.

(7) radioprotective: tea polyphenols, polysaccharide ester and Citrin, can alleviate radiocurable side effect, stop leukopenia, promote leukocyte increasing; Tea polyphenols can absorb 90Sr, makes 90Sr remove bone marrow.So there is the people that the Folium Camelliae sinensis exaggeration is " atom-age beverage ".

(8) tea tannin has convergence, antiinflammation: can be used for intractable ulcer; Contain micro-fluoride in the Folium Camelliae sinensis, the oral cavity of can sterilizing, caries prevention.

(9) smooth muscle: caffeine class, particularly theophylline, owing to suppress phosphodiesterase cAMP is increased, gastrointestinal tract, bronchial smooth muscle there are relaxation effect, so can be used for spasmolytic (biliary tract) and Zhichuan.

The pharmacological action of Radix Platycodonis

(1) eliminates the phlegm: can promote the bronchial mucosa secretions increase for the oral Radix Platycodonis decoct of Canis familiaris L..Be because Radix Platycodonis contains Saponin, can stimulate gastric mucosa, reflexive causes bronchus body of gland secretion increasing, the dilution sputum, and play phlegm-dispelling functions.

(2) blood fat reducing: kikyosaponin can reduce rat liver inner cholesterol content, increases the secretion of cholesterol and cholic acid.

(3) blood sugar lowering: oral Radix Platycodonis water of rabbit or alcoholic extract, blood glucose is descended, to the rabbit diabetes that alloxan causes, hypoglycemic activity is more obvious.

(4) antibacterial: in vitro Radix Platycodonis has inhibitory action to acrothesium floccosum.

(5) other: thick kikyosaponin has calmness, analgesia and refrigeration function.

(6) toxic and side effects: the LD50 of mice and the oral thick kikyosaponin of rat is respectively 420mg/kg and greater than 800mg/kg, and is respectively 22.3mg/kg and 14.1mg/kg during lumbar injection.Heavy dose of orally cause nausea and vomit.The careful usefulness of gastric and duodenal ulcers patient.Radix Platycodonis has stronger haemolysis, thus only suitable oral, can not inject.

Below in conjunction with embodiment, the present invention will be further described.

This cough-relieving, eliminate the phlegm, Asthma capsule, prescription consists of Herba Epimedii selenium, zinc glycyrrhizate, Venenum Bufonis, Radix Physochlainae, Folium Camelliae sinensis, Radix Platycodonis.Concrete reparation technology is as follows:

(1) Herba Epimedii selenium extraction process: (1) crude product Herba Epimedii selenium extraction process: the former medicine of crude product adds 8 times of amount 1% selenic acid liquid, kept 80 ℃ of reflux, extract, 3 hours, the leaching medicinal liquid is put in addition, residue adds 5 times of amount 1% selenic acid liquid again, pressing the Same Way operation extracted 2 hours, multiple leaching medicinal liquid and preceding liquid merge, and gather all selenic acid extracting solution, are condensed into than weighing 1.1～1.2, add 95% ethanol equivalent precipitated impurities, left standstill 12～14 hours, and extracted supernatant liquid filtering, precipitation is with 45% washing with alcohol 2～3 times, the solubility composition washes out in will precipitating, filtrate and washing liquid merge, and reclaim ethanol, and concentrating under reduced pressure is cooled to cream.Promptly get the thick extracted extract of Herba Epimedii selenium.(2) pure product Herba Epimedii selenium extraction process: the thick extracted extract of Herba Epimedii selenium adds 70%4 times of amount ethanol, and reflux 2 hours is filtered, and filtering residue adds 2 times of amount alcohol refluxs 1 hour again, filters, and reclaims ethanol, and 60 ℃ of dryings promptly get pure product Herba Epimedii selenium.(3) epimedium brevicornum polysaccharide selenium extraction process: Herba Epimedii is pulverized coarse powder and is added 5 times of amounts of 75% ethanol, 0.5% selenic acid (Ha2SeO4) reflux 2 hours, filter, extract 3 times with method, merging filtrate is condensed into cream, adds 95% ethanol with being stirred to precipitation, 12 hours after-filtration, reclaim ethanol, continuous 2 times, add 2 times of amounts of water, with DEAE cellulose (phosphate type) column chromatography purification, get pure product epimedium brevicornum polysaccharide selenium.

(2) zinc glycyrrhizate extraction process: (1) thick zinc glycyrrhizate extraction process: thick Radix Glycyrrhizae powder is measured 0.5% zinc carbonate (ZnCO3) seepages with 12 times, continuous 3 times, effusion is concentrated into original volume 1/5 and filters, filtrate adds concentrated sulphuric acid to PH3, the precipitation that filtration is separated out, wash 3 times, dry below 60 ℃, promptly get thick zinc glycyrrhizate (yield 10%).(2) pure product zinc glycyrrhizate extraction process: above gained zinc glycyrrhizate 400g, add 4 times of amount ethanol, reflux 3 hours, filter, filtering residue adds 2 times of amount alcohol heating reflux 2 times, merges all backflow and adds the 10g active carbon, reflux decolour cooling half an hour, filter, filtrate adds ZnCO3 to PH7～7.5, till no solid is separated out.The filtrate precipitation, with the small amount of ethanol washing, drying at room temperature gets zinc glycyrrhizate 250g.(3) glycyrrhiza residue and precipitate extract zinc glycyrrhizate, glycyrrhizic acid calcium, licoflavone, Radix Glycyrrhizae residue and precipitate adds 1% zinc sulfate (ZnSO4) and 70% ethanol is lyase, hot dipping 8 hours, reflux 2 hours, filter, continuous 2 times, merging filtrate reclaims ethanol, be condensed into cream, promptly reclaim zinc glycyrrhizate, glycyrrhizic acid calcium, licoflavone.

Zinc sulfate: it is synthetic that (1) zinc participates in interior 80 plurality of enzymes of body, and pancreas, gonad, activity pituitary all have zinc to participate in.(2) keep the normal development function of male's gland, zinc deficiency can make oligospermia, and impotence generandi forms male sterility.(3) the human body barriers function can be kept and strengthen to zinc, performance defence infection effect.(4) zinc and cardiovascular and cerebrovascular vessel have certain relation, and zinc and cadmium be mutual antagonism in biosystem, and oral zinc can replace cadmium in the arterial wall, and expansion ischemic region blood vessel.(5) zinc has the promotion growth promoter, improves the sense of taste etc., growth retardation during zinc deficiency, and nervous function depletion can have conjunctivitis, stomatitis, glossitis, inappetence, chronic diarrhea etc.(6) zinc counts for much to upgrowth and development of children, and the zinc deficiency visible volume is thin and weak, mental retardation etc.(7) feed ration: 10～15mg/ day, maximum 120mg/ day.

(3) Venenum Bufonis extraction process: (1) Venenum Bufonis concocting method: Venenum Bufonis was advisable with 60% soak with ethanol in 24 hours, Venenum Bufonis is no change before and after steeping in wine system, but total cardenolide content content after steeping in wine system has improved, think and not only help after the steeping in wine system pulverizing, and the enhancing drug effect, and toxicity reduces 30～50%.Mice LD50 is 403.7～540.8mg/kg after the steeping in wine system.(2) Venenum Bufonis is ground into 14～40 mesh sieve powder, and it is best to add 3.75 hours method of 95% alcohol heating reflux.

(4) Radix Physochlainae is extracted Rhizoma Scopoliae Japonicae, Anisodamine extraction process: get Radix Physochlainae 1000g, by seepage method seepage, collect effusion 10000ml with 70% ethanol, reclaim ethanol and be concentrated into 500ml, put separatory funnel defat with petroleum ether 2 times, divide water intaking liquid, steam and remove unrecovered oil ether.Add strong aqua ammonia and regulate PH10～11, gradation is carried most alkaloid with 250ml, 200ml, 150ml chloroform.Combined chloroform liquid, gradation is carried most alkaloid with 2% hydrochloric acid 200ml and 1% hydrochloric acid 300ml, 200ml, 100ml.Merge sour extract, add strong aqua ammonia and transfer PH10～11, gradation is carried most alkaloid with chloroform 300ml, 200ml, 100ml.Combined chloroform liquid is carried most alkaloid with 1% hydrochloric acid 200ml and 0.5% hydrochloric acid 200ml, 100ml respectively.Merge sour extract, transfer PH2～3, heating in water bath is removed residual chloroform, adds 0.2% decolorizing with activated carbon, filters, and is condensed into crystallization.Usual amounts 0.01～0.03mg/kg.

(5) tea extraction process: caffeine technology: Folium Camelliae sinensis adds 8 times of amount 1% sulphuric acid liquid and soaks seepage after 14 hours, continuous 3 times, merging filtrate is concentrated into original volume 1/5 and filters, and filtrate transfers to PH7 with ammonium hydroxide (NH4OH), add 95% ethanol equivalent precipitated impurities, left standstill 12 hours, and extracted supernatant liquid filtering out, precipitation is with 45% washing with alcohol 2～3 times, be condensed into cream, promptly get theophylline and caffeine crystallization.

(6) Radix Platycodonis extract technology: get Radix Platycodonis,, add 8 times of amounts of 55% ethanol and make solvent by the seepage method, flooded 48 hours, with per minute 1～3ml speed seepage, spill fully to institute's soluble components, collect and continue seepage, continuous 3 times, merging filtrate filters, to below 60 ℃, cryoconcentration is dried to extractum to the thick paste shape.

(7) cough-relieving, eliminate the phlegm, the preparation process of Asthma capsule:

Use according to clinical repetition test and checking, select the best safety consumption: Herba Epimedii selenium 50mg/kg/ day; Epimedium flavone 20mg/kg/ day; Epimedium brevicornum polysaccharide selenium 20mg/kg/ day; Radix Glycyrrhizae extract zinc glycyrrhizate 20mg/kg/ day; Venenum Bufonis 0.32mg/kg/ day; Radix Physochlainae extract scopolamine 0.012mg/kg/ day, Anisodamine 0.3mg/kg/ day; Folium Camelliae sinensis extract theophylline 8mg/kg/ day, caffeine 4mg/kg/ day; Radix Platycodonis extract kikyosaponin 50mg/kg/ day amounts to 8622.1mg/50kg/ day, is divided into 18 large size capsules, and each capsule contains 479mg.

This cough-relieving, eliminate the phlegm, the pharmacokinetics of Asthma capsule is:

The oral easy absorption of Venenum Bufonis, effect takes place and disappears all very fast, no cumulative action, finding that liver sausage concentration is higher, secondly be that stomach, the heart, kidney, brain, muscle, blood half-life are short only 7.5 minutes, more through the bile discharge, 24 hours through 4.4% and 1.93% of the urine amount of discharging into, discharge through excrement and morely to account for 43.32% and 28.8%, each tissue content is the highest with the heart, almost all discharges after 24 hours.Scopolamine and Anisodamine excreted in general six hours, and safety range is big.

This cough-relieving, eliminate the phlegm, the indication of Asthma capsule:

Be applicable to cough (acute/chronic bronchitis), rheumatism pyretic pulmonary disease (acute pneumonia pathological changes), breathe heavily disease (obstructive emphysema, pulmonary heart disease, pulmonary insufficiency etc.), bronchial wheezing (bronchial asthma, asthmatic bronchitis), cough up＜cough blood (bronchiectasis) etc.

This cough-relieving, eliminate the phlegm, the untoward reaction of Asthma capsule: one or two people have gastrointestinal reaction (as: feel sick, upper abdomen distension).

This cough-relieving, eliminate the phlegm, the contraindication of Asthma capsule: to this product allergy sufferers, anemia of pregnant woman's forbidding has the careful usefulness of severe cardiac functional defect person.

This cough-relieving, eliminate the phlegm, the usage and the consumption of Asthma capsule: first 2, days three times, if the nonresponder can increase to 4, days three times, each 5 of maximal dose, days 3～4 times, because of this medicine safety range is big, 1～2 of child, or follow the doctor's advice.After heavy dose of stable disease, can reduce to 3～5 of maintenance doses, 3 times/day, determined curative effect.

Claims (2)

1. a cough-relieving, eliminate the phlegm, Asthma capsule, be characterised in that its prescription consists of Herba Epimedii selenium, zinc glycyrrhizate, Venenum Bufonis, Radix Physochlainae, Folium Camelliae sinensis, Radix Platycodonis, specifically constitutes: Herba Epimedii selenium 28.9%; Epimedium flavone 11.6%; Epimedium brevicornum polysaccharide selenium 11.6%; Radix Glycyrrhizae extract zinc glycyrrhizate 11.6%; Venenum Bufonis 0.19%; Radix Physochlainae extract scopolamine 0.007%, Anisodamine 0.178%; Folium Camelliae sinensis extract theophylline 4.68%, caffeine 2.34%; Radix Platycodonis extract kikyosaponin 28.9%.

2. a cough-relieving, eliminate the phlegm, the preparation method of Asthma capsule, be characterised in that concrete reparation technology is as follows:

(1) Herba Epimedii selenium extraction process:

(1) crude product Herba Epimedii selenium extraction process: the former medicine of crude product adds 8 times of amount 1% selenic acid liquid, kept 80 ℃ of reflux, extract, 3 hours, the leaching medicinal liquid is put in addition, residue adds 5 times of amount 1% selenic acid liquid again, press the Same Way operation and extracted 2 hours, multiple leaching medicinal liquid and preceding liquid merge, and gather all selenic acid extracting solution, be condensed into than weighing 1.1～1.2, add 95% ethanol equivalent precipitated impurities, left standstill 12～14 hours, extract supernatant liquid filtering, precipitation is with 45% washing with alcohol 2～3 times, the solubility composition washes out in will precipitating, and filtrate and washing liquid merge, and reclaims ethanol, concentrating under reduced pressure is cooled to cream, promptly gets the thick extracted extract of Herba Epimedii selenium;

(2) pure product Herba Epimedii selenium extraction process: the thick extracted extract of Herba Epimedii selenium adds 70%4 times of amount ethanol, and reflux 2 hours is filtered, and filtering residue adds 2 times of amount alcohol refluxs 1 hour again, filters, and reclaims ethanol, and 60 ℃ of dryings promptly get pure product Herba Epimedii selenium;

(3) epimedium brevicornum polysaccharide selenium extraction process: Herba Epimedii is pulverized coarse powder and is added 5 times of amounts of 75% ethanol, 0.5% selenic acid (Ha2SeO4) reflux 2 hours, filter, extract 3 times with method, merging filtrate is condensed into cream, adds 95% ethanol with being stirred to precipitation, 12 hours after-filtration, reclaim ethanol, continuous 2 times, add 2 times of amounts of water, with phosphate type DEAE cellulose chromatography purification, get pure product epimedium brevicornum polysaccharide selenium;

(2) zinc glycyrrhizate extraction process:

(1) thick zinc glycyrrhizate extraction process: thick Radix Glycyrrhizae powder is measured 0.5% zinc carbonate (ZnCO3) seepages with 12 times, and continuous 3 times, effusion is concentrated into original volume 1/5 and filters, filtrate adds concentrated sulphuric acid to PH3, filters the precipitation of separating out, and washes 3 times, dry below 60 ℃, promptly get thick zinc glycyrrhizate;

(2) pure product zinc glycyrrhizate extraction process: above gained zinc glycyrrhizate 400g adds 4 times of amount ethanol, reflux 3 hours, filter, filtering residue adds 2 times of amount alcohol heating reflux 2 times, merges all backflow and adds the 10g active carbon, reflux decolour cooling half an hour, filter, filtrate adds ZnCO3 to PH7～7.5, till no solid is separated out, the filtrate precipitation, with the small amount of ethanol washing, drying at room temperature gets zinc glycyrrhizate 250g;

(3) glycyrrhiza residue and precipitate extract zinc glycyrrhizate, glycyrrhizic acid calcium, licoflavone: Radix Glycyrrhizae residue and precipitate add 1% zinc sulfate (ZnSO4) and 70% ethanol is lyase, hot dipping 8 hours, reflux 2 hours, filter, continuous 2 times, merging filtrate reclaims ethanol, be condensed into cream, promptly reclaim zinc glycyrrhizate, glycyrrhizic acid calcium, licoflavone;

(3) Venenum Bufonis extraction process:

(1) Venenum Bufonis concocting method: Venenum Bufonis was with 60% soak with ethanol 24 hours;

(2) Venenum Bufonis is ground into 14～40 mesh sieve powder, adds 95% alcohol heating reflux 3.75 hours;

(4) Radix Physochlainae is extracted Rhizoma Scopoliae Japonicae, Anisodamine extraction process: get Radix Physochlainae 1000g, press seepage method seepage with 70% ethanol, collect effusion 10000ml, reclaim ethanol and be concentrated into 500ml, put separatory funnel defat with petroleum ether 2 times, divide water intaking liquid, steam and remove unrecovered oil ether, add strong aqua ammonia and regulate PH10～11, gradation 250ml, 200ml, the 150ml chloroform is carried most alkaloid, combined chloroform liquid, gradation is with 2% hydrochloric acid 200ml and 1% hydrochloric acid 300ml, 200ml, 100ml carries most alkaloid, merge sour extract, add strong aqua ammonia and transfer PH10～11, gradation chloroform 300ml, 200ml, 100ml carries most alkaloid, combined chloroform liquid, use 1% hydrochloric acid 200ml and 0.5% hydrochloric acid 200ml respectively, 100ml carries most alkaloid, merge sour extract, transfer PH2～3, heating in water bath, remove residual chloroform, add 0.2% decolorizing with activated carbon, filter, be condensed into crystallization;

(5) Folium Camelliae sinensis extracts caffeine technology: Folium Camelliae sinensis adds 8 times of amount 1% sulphuric acid liquid and soaks seepage after 14 hours, continuous 3 times, merging filtrate is concentrated into original volume 1/5 and filters, and filtrate transfers to PH7 with ammonium hydroxide (NH4OH), add 95% ethanol equivalent precipitated impurities, left standstill 12 hours, and extracted supernatant liquid filtering out, precipitation is with 45% washing with alcohol 2～3 times, be condensed into cream, promptly get theophylline and caffeine crystallization;

(6) Radix Platycodonis extract technology: get Radix Platycodonis,, add 8 times of amounts of 55% ethanol and make solvent by the seepage method, flooded 48 hours, with per minute 1～3ml speed seepage, spill fully to institute's soluble components, collect and continue seepage, continuous 3 times, merging filtrate filters, to below 60 ℃, cryoconcentration is dried to extractum to the thick paste shape;

(7) capsular preparation process:

Select each composition safety using amount to be: Herba Epimedii selenium 50mg/kg/ day; Epimedium flavone 20mg/kg/ day; Epimedium brevicornum polysaccharide selenium 20mg/kg/ day; Radix Glycyrrhizae extract zinc glycyrrhizate 20mg/kg/ day; Venenum Bufonis 0.32mg/kg/ day; Radix Physochlainae extract scopolamine 0.012mg/kg/ day, Anisodamine 0.3mg/kg/ day; Folium Camelliae sinensis extract theophylline 8mg/kg/ day, caffeine 4mg/kg/ day; Radix Platycodonis extract kikyosaponin 50mg/kg/ day amounts to 8622.1mg/50kg/ day, is divided into 18 large size capsules, and each capsule contains 479mg.