CN104998034A - Chinese herbal medicine combination drug treating livestock respiratory diseases and preparation method thereof - Google Patents

Chinese herbal medicine combination drug treating livestock respiratory diseases and preparation method thereof Download PDF

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CN104998034A
CN104998034A CN201510479049.4A CN201510479049A CN104998034A CN 104998034 A CN104998034 A CN 104998034A CN 201510479049 A CN201510479049 A CN 201510479049A CN 104998034 A CN104998034 A CN 104998034A
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radix
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medicine
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chinese herbal
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王一硕
郭瑞英
周清利
葛会杰
苏慧
李召展
刘海平
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HENAN RUILANTE BIOLOGICAL PHARMACEUTICAL Co Ltd
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HENAN RUILANTE BIOLOGICAL PHARMACEUTICAL Co Ltd
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Abstract

The invention relates to a Chinese herbal medicine combination drug treating livestock respiratory diseases and a preparation method thereof. The Chinese herbal medicine combination drug comprises, by weight, 95-105 parts of white mulberry root bark, 75-85 parts of rhizoma anemarrhenae, 75-85 parts of apricot kernels, 110-130 parts of gypsum, 55-65 parts of phillyrin, 55-65 parts of radix glycyrrhizae, 95-105 parts of radix scutellariae, 55-65 parts of platycodon grandiflorum and 55-65 parts of bupleurum. The combination drug is prepared on the basis of the traditional Chinese medicine theory in the principle of drug matching, and modern pharmacological research results are taken as reference. The combination drug has the effects of dispelling wind and heat, clearing the lung and calming panting, relieving sore-throat and diminishing swelling, resolving superficies syndrome with pungent and cool natured drugs and clearing heat and detoxifying. The combination drug is mainly used for treating the livestock respiratory diseases caused by single pathogens or various pathogens, and is an innovation of veterinary drugs treating the livestock respiratory diseases. The combination drug has the advantages of being rich in raw material, low in price, safe in drug use, free of toxic and side effects and good in use effect.

Description

A kind of Chinese herbal medicine composition of medicine for the treatment of livestock and poultry respiratory disease and preparation method thereof
Technical field
The invention belongs to pharmaceutical technology sectors, be specifically related to a kind of Chinese herbal medicine composition of medicine for the treatment of livestock and poultry respiratory disease and preparation method thereof.
Background technology
In recent years, the intensive chicken farm in the many areas of China, pig farm, in the autumn, season in winter two, there is the infectious disease based on respiratory symptom, livestock and poultry respiratory disease refers under merchandized handling condition, with virus, antibacterial, mycoplasma is the respiratory tract disease that the infection that causes of the many reasons such as cause of disease and adverse environmental factors or mixed infection cause, this disease is propagated rapidly, huge economic loss is caused to raiser, during application this type of disease of antibiotic therapy, because pathogenic factor its Different therapeutical effect different is very large, and it is single for a long time, apply certain antibiotic, be easy to produce Resistant strain and affect its curative effect, when antibacterial and mycoplasma and virus mixed infection, antibiotic curative effect is unsatisfactory, immunity inoculation react poultry body also can be hindered to copy Respiratory Disease Vaccine live virus limitation capability, affect immune response, produce the low or nothing of antibody horizontal, for infectious bronchitis of fowl, the sickness rate of primary disease is high, the mortality rate of chickling can reach more than 25%, and laying rate of laying hen can drop to half, and produces soft egg and abnormal-shape egg.And the mycoplasma of pig is breathed, disease also claims mycoplasmal pneumonia of swine, pig endemic conditions pneumonia, it is a kind of high degree in contact chronic respiratory infectious disease of pig, caused by mycoplasma hyopneumoniae, primary disease is distributed in all over the world, and sickness rate is high, and mortality rate is low, clinical cardinal symptom is cough and asthma, can not normal growth, the various medicine of above-mentioned disease is all without direct curative effect, and application antibiotic prevents secondary infection only.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art and provide that a kind of raw material sources are extensive, cheap, preparation technology's Chinese herbal medicine composition of medicine of simply treating livestock and poultry respiratory disease and preparation method thereof.
Technical scheme of the present invention is: a kind of Chinese herbal medicine composition of medicine for the treatment of livestock and poultry respiratory disease, and it is prepared from according to following weight proportion by each crude drug: described composition of medicine is made up of following proportioning raw materials: Cortex Mori 95-105 parts, the Rhizoma Anemarrhenae 75-85 parts, Semen Armeniacae Amarum 75-85 parts, 110-130 parts, Gypsum Fibrosum, Fructus Forsythiae 55-65 parts, 55-65 parts, Radix Glycyrrhizae, Radix Scutellariae 95-105 parts, Radix Platycodonis 55-65 parts and Radix Bupleuri 55-65 parts.
A kind of as claimthe preparation method of the Chinese herbal medicine composition of medicine of the treatment livestock and poultry respiratory disease described in 1, described preparation method comprises the steps:
Step 1: selection: choose Cortex Mori, the Rhizoma Anemarrhenae, Semen Armeniacae Amarum, Gypsum Fibrosum, Fructus Forsythiae, Radix Glycyrrhizae, Radix Scutellariae, Radix Platycodonis and Radix Bupleuri according to said ratio and be placed in container;
Step 2: soak: the mixture getting the water soaking Cortex Mori of 12 times of weight of step 1 Chinese crude drug gross mass, the Rhizoma Anemarrhenae, Semen Armeniacae Amarum, Gypsum Fibrosum, Fructus Forsythiae, Radix Glycyrrhizae, Radix Scutellariae, Radix Platycodonis and Radix Bupleuri, soak time is 15-20min;
Step 3: first time lixiviate: by the mixture boiled after adding water in step 2, then the 25-35min that simmers in water;
Step 4: first time filters: the mixture obtained in step 3 is filtered, and collects first time filtrate, obtain first time filtering residue;
Step 5: second time lixiviate: the first time filtering residue after step 4 being filtered boils after adding the water of 10 times of weight of step 1 Chinese crude drug gross mass, then the 25-35min that simmers in water;
Step 6: second time is filtered: the mixture obtained in step 5 is filtered, and collect second time filtrate, obtain second time filtering residue;
Step 7: third time lixiviate: the second time filtering residue after step 6 being filtered boils after adding the water of 10 times of weight of step 1 Chinese crude drug gross mass, then the 15-25min that simmers in water;
Step 8: third time filters: the mixture obtained in step 7 is filtered, and collects third time filtrate;
Step 9: merge, concentrate: the first time filtrate that step 4, step 6 and step 8 are obtained, second time filtrate and third time filtrate merging, and the mixed liquor after merging is concentrated, the ratio choosing medical material gross mass (Kg) in the volume (L) of the concentrated solution after concentrated and step 1 is 2:1;
Step 10: storage: concentrated solution step 9 obtained collects storage at normal temperatures and pressures;
Described composition of medicine is made up of following proportioning raw materials: Cortex Mori 95 parts, the Rhizoma Anemarrhenae 75 parts, Semen Armeniacae Amarum 75 parts, 110 parts, Gypsum Fibrosum, Fructus Forsythiae 55 parts, 55 parts, Radix Glycyrrhizae, Radix Scutellariae 95 parts, Radix Platycodonis 55 parts and Radix Bupleuri 55 parts.
Described composition of medicine is made up of following proportioning raw materials: Cortex Mori 100 parts, the Rhizoma Anemarrhenae 80 parts, Semen Armeniacae Amarum 80 parts, 120 parts, Gypsum Fibrosum, Fructus Forsythiae 60 parts, 60 parts, Radix Glycyrrhizae, Radix Scutellariae 100 parts, Radix Platycodonis 60 parts and Radix Bupleuri 60 parts.
Described composition of medicine is made up of following proportioning raw materials: Cortex Mori 105 parts, the Rhizoma Anemarrhenae 85 parts, Semen Armeniacae Amarum 85 parts, 130 parts, Gypsum Fibrosum, Fructus Forsythiae 65 parts, 65 parts, Radix Glycyrrhizae, Radix Scutellariae 105 parts, Radix Platycodonis 65 parts and Radix Bupleuri 65 parts.
The Chinese herbal medicine compound formulation that a certain amount of sucrose, Mel, sodium cyclamate and flavoring orange essence composition make treatment livestock and poultry respiratory disease is added in described concentrated solution step 10 obtained.
The present invention has the following advantages: the present invention is based on Traditional Chinese medical theory, with reference to modern pharmacological research achievement, make by drug matching principle, there is dispelling wind and heat pathogens, clearing lung, relieving asthma, relieving sore throat and diminishing swelling, relieving the exterior syndrome with drugs of pungent in flavor and cool in nature, effect of heat-clearing and toxic substances removing, cure mainly the livestock and birds respiratory disease caused by single pathogen or multiple pathogens mixed infection, be treatment livestock and birds respiratory disease herbal medicine thing on innovation, the present invention has abundant raw material, cheap, drug safety, has no side effect, the advantage that result of use is good.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is further illustrated.
Embodiment 1
The present invention in the specific implementation, can adopt following composition of raw materials: Cortex Mori 95g, Rhizoma Anemarrhenae 75g, Semen Armeniacae Amarum 75g, Gypsum Fibrosum 110g, Fructus Forsythiae 55g, Radix Glycyrrhizae 55g, Radix Scutellariae 95g, Radix Platycodonis 55g and Radix Bupleuri 55g.
Embodiment 2
The present invention in the specific implementation, can adopt following composition of raw materials: Cortex Mori 100g, Rhizoma Anemarrhenae 80g, Semen Armeniacae Amarum 80g, Gypsum Fibrosum 120g, Fructus Forsythiae 60g, Radix Glycyrrhizae 60g, Radix Scutellariae 100g, Radix Platycodonis 60g and Radix Bupleuri 60g.
Embodiment 3
The present invention in the specific implementation, can adopt following composition of raw materials: Cortex Mori 105g, Rhizoma Anemarrhenae 85g, Semen Armeniacae Amarum 85g, Gypsum Fibrosum 130g, Fructus Forsythiae 65g, Radix Glycyrrhizae 65g, Radix Scutellariae 105g, Radix Platycodonis 65g and Radix Bupleuri 65g.
In the invention described above prescription:
Cortex Mori is the dry root bark of moraceae plants Mulberry MorusalbaL.; The property of medicine is sweet, cold, returns lung meridian; Effect is eliminating pathogen from the lung for relieving asthma, inducing diuresis to remove edema, for dyspnea and cough due to lung-heat, and edema distension oliguria, appearance skin edema;
Modern study: Sang Su (mulberrin), mulberrochromene (mulberrochromene), cyclomulberrin (cyclomulberrin), cyclomulberrochromene (cyclomulberro-chromene), Morusin (morusin), cyclomorusin (cyclomorusin), oxidation dihydro Morusin (oxydihydromomsin), Phellinus igniarius (L. ex Fr.) Quel. ketone (kuwanon) A, B, C, D, E, F, G (i.e. albaninF, moraceninB), H (i.e. albaninG, moraceninA), I, K, L, Y, Z, moracenin (moracenin) C, D, sanggenon (sffnggenone) A ~ P, again containing Mulberrofuran (mulberrofuran) A, B, C, K, N, 0, M, P, Q, the acid of birch skin, Coumarins: 5, umbelliferone (5,7-dihydmxycoumarin) umbelliferone (umbelliferone), scopoletin (i.e. scopoletin, scopoletin), the compositions such as hyoscyami lactone, polysaccharide: mucoitin, Mulberry polysaccharide, chitin, chitosan.Also containing α-and β-amyrin, sitoesterol, volatile oil, tannin etc.
1, alcohol extract 5 ~ the 6mg/kg of hypotensive effect Cortex Mori, to anesthetized rabbit, the decline that dog duodenal administration can make animal blood pressure obvious and lasting, and it is oral to the animal 20g/kg of experimental renal hypertension, also obvious hypotensive effect can be produced, cut off both sides vagus nerve or cut off spinal cord in 5th ~ 6 cervical vertebras, its hypotensive effect is constant, Cortex Mori ether, the extracting solution of hot water or warm methanol, during to rabbit hemostasis 1g (crude drug)/kg, blood pressure drops 2 ~ 3.3kPa can be made, from Cortex Mori, raising a kind of material, [fusing point (decomposition) is 144 DEG C, to rabbits after intravenous note 10mg/kg, blood pressure significantly declines immediately, cut off neck vagus nerve or cervical vertebra, this effect still exists, therefore may be acetylcholine sample material in deduction extract, Cortex Mori extract can suppress isolated frog heart, excited rabbits infestines, and the effect of reducing blood pressure can be resisted by atropine, this kind of blood pressure lowering is pointed out to suppress, may vasomotor center be inhibit and occur, blood pressure lowering seemingly has increase to renal blood flow simultaneously, isolated sanggenon quiet note rabbit from Cortex Mori, can significantly blood pressure lowering, cyclomorusin, Cortex Mori furan C etc. has hypotensive effect.
2, diuresis Cortex Mori decoct 2g/kg, oral or Cortex Mori aqueous extract and n-butanol extract 300 ~ 500mg/kg to rabbit, to Oral Administration in Rats or lumbar injection, all there is significant diuresis, (Na, K output in 6 hours, all significantly increases, and this product has significant diuresis to make urine volume and the chloride in urinating.
3, the extract of the fat-soluble solvent such as petroleum ether, ether, ethyl acetate of sedation and analgesia effect Cortex Mori is to the quiet note of mice, the spontaneous activity of mice can be reduced, and have anticonvulsant effect, the Cortex Mori severe edema due to hypofunction of the spleen or the above intraperitoneal injection of mice of n-butanol extract 50mg/kg, animal spontaneous activity can be made to reduce, sense of touch and pain sensation reaction reduce, platycoria, and the generation that slightly can suppress mice galvanic shock.
4, antiinflammatory action Cortex Mori water extract has inhibitory action to the swollen feet caused by Oral Administration in Rats or injection on Carrageenan and glucosan.
5, antibacterial action Cortex Mori decoct has stronger inhibitory action to staphylococcus aureus, also slight inhibitory action is had to Bacillus typhi and shigella flexneri, Cortex Mori furan A all has stronger bacteriostatic activity to staphylococcus aureus, mycobacterium, and cyclomorusin also has antifungic action.
6, contained acidic materials in anticoagulant Cortex Mori, can affecting the cyclooxygenase in platelet, thus inhibit the biosynthesis of TBX2, or suppress the generation of 12-HETE, by changing arachidonic metabolism, affecting hematoblastic gathering.
7, be separated in blood sugar reducing function Cortex Mori and confirm blood sugar reducing component Moranoline (de-dioxy imido grpup Fructus Vitis viniferae alcohol) and MoranA sugar reducing substance, through overtesting, confirm, the hyperglycemia mice (blood glucose 250 ~ 450mg/dL) of MoranA to model induced by alloxan has dose-dependent hypoglycemic effect.
8, other effect Cortex Mori hot water extract in vitro tests, be about 70% to the suppression ratio of human cervical carcinoma JTC-26 strain, there is inducement interferon effect, the excited isolated rabbit uterus of Cortex Mori energy, the secretion of slight promotion rabbit parotid gland, and can phosphodiesterase be suppressed, there is catharsis effect, Cortex Mori water extract has slight antitussive effect to Cavia porcellus, n-butanol extract also has antitussive effect, also having certain cooling effect, is that the antipyretic cephalocathartic syrup of principal agent also has antipyretic, expelling phlegm for arresting cough effect preferably with Cortex Mori.
The Rhizoma Anemarrhenae is the dry rhizome of liliaceous plant Rhizoma Anemarrhenae AnemarrhenaasphodeloidesBge., and the property of medicine is bitter, sweet, cold, returns lung, stomach, kidney channel, effect is clearing away heat-fire, nourshing Yin and drynsessmoistening prescription, for fever caused by exogenous pathogenic factors, and high hot excessive thirst, lung-heat type cough, osteopyrexia and fever, interior-heat is quenched one's thirst, dryness of the intestine constipation.
Modern study: containing Total saponin about 6% in zhimusaponin A-III rhizome, wherein there is zhimusaponin (Timosaponin) A-I, A-II, A-III, A-IV, B-I and B-II, wherein zhimusaponin A-I is Sa Ersa ruscogenin β-D-galactopyranosyl glucoside, zhimusaponin A-III is the disaccharidase glycoside that Sa Ersa ruscogenin and timobiose (Timobiose) are combined into, ruscogenin in Asphodeloides Bge Rhizome has Sa Ersa ruscogenin (Sarsasapogenin), markogenin (Markogenin), new gitogenin (Neogitogenin), the Saponin Chinonin (Asphonin) separated from the Rhizoma Anemarrhenae in the past is that right that examines Saponin, zhimusaponin A-III, A-IV, the mixture of B etc., also the soaping agents compositions such as smilagenin (Smilagenin) are isolated, Mengiferin (Mangiferin still containing flavonoid, Chi-monin), isomangiferin (Isomangiferin), the choline (Choline) of alkaloids, niacin amide (Nicotinamide), the tannic acid (Tannicacid) of organic acid, nicotinic acid (Nicotinicacid) and four kinds of anemarans (AnemarnA, B, C, D), in addition still Determination of multiple metal elements and lymphatic temperament, the reducing sugar etc. such as iron content, zinc, manganese, copper, chromium, nickel.
1, resisting pathogenic microbes effect experiment in vitro shows: Rhizoma Anemarrhenae decoct has stronger inhibitory action, to dysentery bacterium, Salmonella paratyphi, escherichia coli, bacillus subtilis, vibrio cholera, Bacillus proteus, diphtheria corynebacterium, Diplococcus pneumoniae, beta hemolytic streptococcus, white to staphylococcus, Bacillus typhi candidiasisdeng the inhibitory action also had in various degree, Rhizoma Anemarrhenae ethanol extract, ether extractum and ether extractum add the coarse crystallization of gained after acetone treatment, to general, visit the H37RV Bacillus tuberculosis subspecies that culture medium is cultivated and have stronger inhibitory action, wherein the inhibitory potency of the anti-mycobacterium tuberculosis of ether extractum is the highest, Saponin is then without effect, but there is report from the Rhizoma Anemarrhenae, raise a kind of aqueous saponin, to tubercule bacillus, especially right candida albicansthere is stronger inhibitory action; And another kind of flavone crystallization, also there is inhibitory action to tubercule bacillus, to guinea pig experimental tuberculosis with 3% Rhizoma Anemarrhenae drug foods treatment 3 ~ 4 months, have good therapeutic effect; Also can alleviate the pulmonary lesion of experimental M mice, but mortality rate does not reduce; As drug level is brought up to 5%, then pulmonary tuberculosis index (situation of reflection lungs cardinal principle pathological changes) can close to isoniazid, but mortality rate comparatively matched group is higher, may be because of the toxicity of medicine own comparatively large caused by, in addition, the Rhizoma Anemarrhenae decoct of 8% ~ 20% concentration also has bacteriostasis to common pathogenic dermatophytosises such as trichophyton, homocentricity trichophyton, trichophytons in husky uncle's culture medium, and also have report to point out, zhimusaponin has molluscicide effect.
2, refrigeration function Rhizoma Anemarrhenae extractum 4g/kg subcutaneous injection, can prevent and treat the high heat of escherichia coli caused rabbit, and persistent, in Asphodeloides Bge Rhizome, contained Saponin has and obviously reduces the consumption rate caused by thyroxine and increase and suppress the effect of Na+K+ATP enzymatic activity.
3, nourishing YIN to lower pathogenic fire Chinese medicine Radix Rehmanniae Rhizoma Anemarrhenae glycyrrhiza decoction or single medicinal material are wherein taken on the rat that affects of 17-hydroxy-11-dehydrocorticosterone effect, all can make the blood plasma suppressed by dexamethasone hydrocortisoneconcentration raises, and has the effect preventing atrophy of adrenal gland, and Radix Rehmanniae Rhizoma Anemarrhenae glycyrrhiza decoction and hormone are taken simultaneously, can reduce the side effect of hormone, and Sapogenin from Zhimu (chinaroot greenbrier sapogenin) is similar to Rhizoma Anemarrhenae water decoction, can obviously reduce high thyroxinstate mouse brain beta-receptor RT value, but on affinity without impact, the weight loss of this state mice can also be improved significantly.
4, after Rhizoma Anemarrhenae dry extract (6g/kg) is injected to normal rabbits to the impact of blood glucose, on blood glucose without impact, alcohol extract can cause temporary blood glucose to raise, Rhizoma Anemarrhenae water logging extract, the blood sugar level of normal rabbit can be reduced, particularly more remarkable to the effect of four oxygen close pyridine Diabetic Rabbits, white tiger adds the ginseng soup (Rhizoma Anemarrhenae, Radix Ginseng, Radix Glycyrrhizae) extract 0.5 ~ 1g/kg lumbar injection, also have tissue of experimental diabetic mice and fall hypoglycemic effect, 6 hours decline 120mg% after administration, to normal rat, the Rhizoma Anemarrhenae can not promote the oxidation of glucose, though can diaphragm be promoted, fatty tissue is to the picked-up of glucose, glycogen content in diaphragm is slightly increased, but liver glycogen content decreases, to the mice of experimental (alloxan) diabetes, lumbar injection Rhizoma Anemarrhenae aqueous extract 0.15g/kg5 hours blood glucose decline 200mg%, in urine, ketoboidies reduces.
5, other effect Rhizoma Anemarrhenae extractum do not make significant difference to pregnant rabbit isolated uterine, from Xiline Zhimu rhizome, get cupreol treatment Skin Squamous Cell Carcinoma, cervical cancer have good therapeutic effect and have no side effect, zhimusaponin antineoplastic action mechanism is relevant with the strong inhibition effect of the pump of its cell membrane, nicotinic acid contained in the Rhizoma Anemarrhenae, there is the effect maintaining skin and neurological health and facilitating digestion road function, the Mengiferin raised from Rhizoma Anemarrhenae leaf has obvious choleretic effect, also can anticoagulant.
Semen Armeniacae Amarum is the dry mature seed of rosaceous plant Prunus armeniaca L.var.ansu Maxim. PrunusarmeniacaL.var.ansuMaxim, Siberia Fructus Pruni PrunussibiricaL., prunus mandshuricaKoehne Prunusmandshurica (Maxim.) Koehne or Fructus Pruni PrunusarmeniacaL., the property of medicine is bitter, tepor, slightly poisonous, return lung, large intestine channel, effect is sending down the abnormal ascending QI relieving cough and asthma, and loosening bowel to relieve constipation, for cough and asthma, fullness in the chest abundant expectoration, dryness of the intestine constipation.
Modern study: containing amygdalin (amygdalin) about 3%, fatty oil about 50%, and containing emulsin (emulsin), amygdalase (amygdalase), prunase (prunase), oxynitrilase (oxynitrilase), and soluble protein, add water after seed grinding placement, amygdalin, by the effect of emulsin, generates hydrocyanic acid, benzaldehyde and glucose.
1, antitussive, containing amygdaloside in antiasthmatic effect Semen Armeniacae Amarum, amygdaloside can be hydrolyzed by the emulsin of enteric microorganism enzyme or the contained Semen pruni armeniacae of Semen Armeniacae Amarum itself in vivo, produces hydrocyanic acid and the benzaldehyde of trace, has inhibitory action, reach antitussive to respiratory center, antiasthmatic effect, " book on Chinese herbal medicine is looked for the truth " records " energy of the existing dispersing wind-cold of Semen Armeniacae Amarum has the therapeutic method to keep the adverse QI flowing downwards to remove the power of breathing heavily again ", is apt to relieving cough and resolving phlegm and relievings asthma, coughing to the chief complaint of lung system, abundant expectoration, pant and have strong specific aim, therefore doctor it can be used as lung system medication to use at all times, no matter internal injury diseases caused by exogenous pathogenic factor, new sick obstinate disease, allly relates to lungs, multiplex it, adopt the test of guinea pig in vitro organ, almond water extracting solution can reduce the sensitivity that organ irritates ammonia, to antihistamine, acetylcholine, barium chloride, to the excitation of tracheal smooth muscle, has obvious antitussive action, and adopting SO2 to cause the method for coughing proves, to mouse stomach amygdaloside 1mg/kg, 10mg/kg, after 100mg/kg keeps 30min, it is respectively 26% to the suppression ratio of cough frequency, 22.8%, 25.3%.The effect of gavage Semen Armeniacae Amarum extract 48.3mg/kg is stronger than equivalent amygdaloside by 39.7%, Semen Armeniacae Amarum is conducive to pulmonary respiratory function because promoting the synthesis of pulmonary surfactant (PS), Semen Armeniacae Amarum can not only promote the synthesis of PS, and can improve the various physiology and biochemistry index about lung (as total phospholipids and pathological section etc. in lung homogenate, edema caused by the lung disorder amount, bronchial lavage).
2, to the effect Semen Armeniacae Amarum bitter in the mouth therapeutic method to keep the adverse QI flowing downwards of digestive system, and be rich in fatty oil, fatty oil can improve the lubrication of intestinal contents to mucosa, therefore Semen Armeniacae Amarum has the function of loosening bowel to relieve constipation, amygdaloside is while forming hydrocyanic acid through enzyme action breaks, also benzaldehyde is produced, the latter can suppress pepsic activity, thus affect digestive function, the pepsin hydrolyzate of aqua armeniacae insoluble portion is with the rat administration of the dosage of 500mg/kg to carbon tetrachloride process, find that it can press down AST, the rising of ALT level and hydroxyproline content, and suppress the prolongation of euglobulin lysis time, the pepsin hydrolyzate of aqua armeniacae insoluble portion can suppress the hypertrophy of Hepar Mus connective tissue, but the Mus AST that D-galactosamine causes can not be suppressed, ALT level raises.
3, antiinflammatory, the amygdalate water extract of analgesic activity defat to caused by acetic acid mouse writhing reaction and cotton balls caused by rat granulomatous inflammation be formed with inhibitory action, by rat joints of foot edema method, the water soluble protein composition KR-A of intravenous injection 40mg/kg Semen Armeniacae Amarum, inflammation-inhibiting effect is had during KR-B5mg/kg, show by mice naphthoquinone induced pain model test, during KR-A or KR-B intravenously administrable 5mg/kg, press down pain rate and be respectively 40.7% and 58.2%, they are swollen to Rat Carrageenan colloidality foot, the ED50 of oral uptake is respectively 13.9mg/kg and 6.4mg/kg, hot plate method in mice and acetic acid writhing method confirm, amygdaloside has analgesic activity, but be different from the analgesics of morphine, amygdaloside decomposes the benzaldehyde quiet Benzoinum condensing enzyme effect produced and generates Benzoinum, Benzoinum has analgesic activity, therefore the domestic people of having can remove the misery of patient with Semen Armeniacae Amarum treatment advanced liver cancer, even not needing of having takes analgesic.
4, antitumor action early in the twentieth century amygdaloside separate from Semen Armeniacae Amarum first, amygdaloside is used for controlling Semen Armeniacae Amarum in the U.S. and treats tumor by nineteen twenty first, doctor ErnestKrebs is first people in the U.S., amygdaloside being used for medicine, and it is called laetrile, though start amygdaloside in the U.S., Mexico etc. from the 1950's countrywidespread is used for treating tumor, commodity are called laetrile or laetrile, but about the antitumor action of amygdaloside does not obtain admitting of FDA, there is dispute at academia always, there are two kinds of diametrically opposite views, a favorable side thinks, amygdaloside is a kind of laetrile, there is the effect of prevention and therapy tumor, and some theoretical and test datas are proposed, as thought, tumor cell anaerobic degradation is preponderated, end product is lactic acid, slant acidity environmental benefits is in the activity improving beta-glucosidase, impel amygdaloside in tumor cell, decomposite more benzaldehyde and hydrocyanic acid, and the selectivity produced tumor cell kill and woundeffect, viewpoint is but thought in contrast to this, and amygdaloside is not vitamin, antitumaous effect is not had yet, even or noxious substance, though the antitumor action of relevant amygdaloside is still in arguement, comprise Belgium, Germany, Italy, Mexico and Philippine more than 20 individual countryin, manufacture and use amygdaloside to be legal, about the antitumor curative effect of Semen Armeniacae Amarum, all there is a large amount of report both at home and abroad, but result is not the same, the suppression ratio of thick agent to Human cervical tumor JTC-26 strain of assistant Teng Zhaoyan (1979) report Semen Armeniacae Amarum hot water extract is 50%-70%, the result of study of Fang Wenlong etc. (1986) shows, Semen Armeniacae Amarum extract lumbar injection or gavage, be that first-class (1987) result of the test of 61.7%-77.1% car literary composition shows to the suppression ratio of hepatocarcinoma and sarcoma 180, the antitumor effective ingredient extracted from Semen Armeniacae Amarum is to transplanted hepatoma mouse peritoneal injection 300mg/kg, 400mg/kg, 600mg/kg, its tumor control rate is respectively 72.0%, 60.8%, 51.0%.Freely Semen Armeniacae Amarum is absorbed to mice, the growth of ehrlich ascites cell can be suppressed, and make life span extension, also have report amygdaloside can prevent and treat the hepatocarcinoma of N-nitrosodimethylamine induction, tumor stove is reduced, but Mai Weiqi etc. (1981) extract amygdaloside (10% aqueous solution) from Semen Armeniacae Amarum carries out animal experiment, result shows rat liver cancer, S180 etc. are all without bacteriostatic activity, by NCI(American Cancer Society) human cases of relevant amygdaloside to cancer curative effect that initiate observe and terminated in 1978 but do not draw obvious conclusion, the U.S. has carried out multiple frontier nature clinical trial in nineteen eighty-two, think that laetrile does not have the clinical value of Therapeutic cancer.
Gypsum Fibrosum is Sulfates mineral anhydrite race Gypsum Fibrosum, main containing hydrous calcium sulfate (CaSO42H2O) wherein CaO32.5%, SO346.6%, H2O20.9%; Often accompany Organic substance, sulfide etc., and containing a small amount of aluminum, silicon, magnesium, ferrum and the element such as micro strontium, barium, the property of medicine is sweet, pungent, in Great Cold, attaches to the lung and stomach meridians, effect: clearing away heat-fire, relieving restlessness is quenched the thirst, for fever caused by exogenous pathogenic factors, high hot excessive thirst, dyspnea and cough due to lung-heat, the high Sheng of stomach-fire, headache, toothache.
1, plaster of paris decoct (1: 1) is injected in artificial fever animal, has refrigeration function.
2, rabbit pulmonary alveolar macrophage obviously to be strengthened in vitro in culture experiment engulfability.
3, to the Isolated Toad heart and Cor Leporis, Small Dose Excitement, heavy dose of suppression.
4, Gypsum Fibrosum decoct has the effect of reduction HBV DNA (HBVDNA) content.
5, Gypsum Fibrosum Preparatum external can restrain mucosa, reduces secretion.
Fructus Forsythiae is the dry fruit of Oleaceae plants Fructus Forsythiae Forsythiasuspensa (Thunb.) Vahl, and the property of medicine is bitter, is slightly cold, return lung, the heart, small intestine meridian, effect is heat-clearing and toxic substances removing, dispersing swelling and dissipating binds, dispelling wind and heat pathogens, for carbuncle, scrofula, acute mastitis, erysipelas, anemopyretic cold, epidemic febrile disease from the beginning of, warm people battalion, high hot excessive thirst, coma sends out speckle, the puckery pain of pyretic stranguria.
Modern study: containing forsythol (Forsythol), forsythin (Phillyrin), phillygenin (Phillygenin), oleanolic acid (Oleanolicacid), betulic acid (Betulinicacid), ursolic acid (Ursolicacid), pinoresinol (Pinoresinol), sterol compound C49H70-80O6. horse tongue resinol glycoside (Matairesinoside), still containing multiple hydro carbons, aldoketones, alcohol ester ethers volatile ingredient: australene (α-Pinene), camphene (Camphene), nopinene (β-Pinene), p-ymene (p-Cymene), limonene (Limonene), γ-terpinene (γ-Terpinene), β-phellandrene (β-Phellandrene), myrcene (Myrcene), β-ocimene (β-Ocimene), Camphora (Camphor), geranial (Geranial), Borneolum Syntheticum (Borneol), α-terpinol (α-Terpineol), safrole (Safrole), linalool (Linalool), Terpinen-4-ol (Terpinen-4-ol), nor-lapachol (Norlapa-chol) and coumarin, rutin etc.
1, antibacterial action Fructus Forsythiae concentrated decotion has antibacterial action in vitro, Bacillus typhi can be suppressed, Salmonella paratyphi, escherichia coli, dysentery bacterium, diphtheria corynebacterium and vibrio cholera, staphylococcus, streptococcus etc., Fructus Forsythiae bacteriostasis in vitro and Flos Lonicerae broadly similar, for main component antibacterial in Lonicerae and Forsythiae Powder, Flos Lonicerae is to Salmonella, particularly the inhibitory action of Bacillus typhi and Hemolytic streptococcus seemingly exceedes Fructus Forsythiae, and to dysentery bacterium, the suppression of staphylococcus aureus then with Fructus Forsythiae seemingly better, the two conbined usage, synergism is there is no in test tube, with Rhizoma Coptidis, the compound recipe of Radix Scutellariae composition, In Vitro Bacteriostasis than during alone Fructus Forsythiae according to Yun Gengqiang, effective ingredient research antibacterial in Fructus Forsythiae is few, forsythol is 1:5120 to the Mlc of staphylococcus aureus in test tube, be 1:1280 to dysentery bacterium, be 1:640 to diphtheria corynebacterium and paratyphoid fever (first) bacillus, it may be antibiotic effective ingredient, spend and have certain curative effect to mouse experiment tuberculosis, then invalid to Cavia porcellus, in addition, also reported the effect of its anti-mycobacterium tuberculosis in test tube and clinically, the alcohol extract of Fructus Forsythiae has anti-leptospira effect in vitro, its intensity is not as good as Rhizoma Coptidis, Herba Salviae Plebeiae or Flos Lonicerae, Radix Scutellariae, and and Cortex Phellodendri, Rhizoma Paridis is similar, Fructus Forsythiae water logging agent (1:5) is in vitro to some inhibitory action of star nocardia, the ethanol of Forsythia koreana fruit, acetone extract and the resin proposed from F.intermedia have antifungic action.
2, other effect Fructus Forsythiaes can suppress Folium Digitalis Purpureae to the intravenous emetic action of Columba livia, reduce vomiting number of times, but do not change the incubation period of vomiting, it is similar that crash the effect after two hours of effect and injection chlorine third is told in its town, it can suppress again the vomiting caused by dog subcutaneous injection apomorphine, therefore infer that the chemoreceptor trigger zone that action principle may be suppression medulla oblongata is told in its town, containing oleanolic acid (having another name called olive folic acid) in the peel of Fructus Forsythiae, therefore there are heart tonifying, diuresis.
Radix Scutellariae is the dry root of labiate Radix Scutellariae ScutellariabaicalensisGeorgi, and the property of medicine is bitter, cold, returns lung, gallbladder, spleen, large intestine, small intestine meridian, effect is heat clearing and damp drying, eliminating fire and detoxication, hemostasis, antiabortive, for hygropyrexia, heat-damp in summer, vomiting and nausea uncomfortable in chest, damp and hot feeling of fullness, dysentery, jaundice, cough due to lung-heat, high hot excessive thirst, heat in blood tells nosebleed, carbuncle sore tumefacting virus, frequent fetal movement.
Modern study: scutellariae,radix is containing flavone compound: baicalin (baicalein), neobaicalein (neobaicalein), i.e. skullcapflavone II (skullcapflavone II), baicalin (baicalin), wogonin (wogonin), wogonoside (wogono-side), oroxylin A(oroxylin, oroxylinA), 7-methoxyl group baicalin (7-methoxbaicalein), skullcapflavone (skullcapflavone) I, dihydro oroxylin A(dihydrooroxylinA), chrysin (chrysin), 2, 5, 8-trihydroxy-7-methoxy flavone (2, 5, 8-trihydroxy-7-methoxy-flavone), 2, 5, 8-trihydroxy-6, 7-dimethoxy flavone (2, 5, 8-trihydroxy-6, 7-dimethoxyflavone), 4, 5, 7-trihydroxy-6-methoxy flavanone (4, 5, 7-trhydroxy-6-methoxyflavanone), 2, 3, 5, 6, 7-penta hydroxy group flavanone (2, 3, 5, 6, 7-pentahydroxyflavanone), wogonin-5-β-D-Glucose glycoside (wogonin-5-β-D-glucoside), 2-(3-hydroxyl-4-methoxyphenyl)-ethyl-1-O-α-L-rhamanopyranosyl (1 → 3)-β-D(4-Resina Ferulae acyl group)-glucose (2-(3-hydroxy-4-methoxyphenyl) ethyl-1-O-α-L-rhamnosyl(1 → 3)-β-D-(4-feruloyl) glucoside), chrysin-6-C-α-L-arabinose glycoside (chrysin-6-C-β-D-glucoside-8-C-β-L-arabinoside), chrysin-6-C-α-L-arabinose glycoside-8-C-β-D-Glucose glycoside (chrysin-6-C-α-L-arabi-noside-8-C-β-D-glucoside), (2S)-2, 5, 6, 7-tetrahydroxy flavanone ((2S)-25, 6, 7-terahydroxyflavanone), 5, 7, 2, 6-kaempferol (5, 7, 2, 6-tetrahydroxyflavone), 5, 8-dihydroxy-6, 7-dimethoxy flavone (5, 8-dihydroxy-6, 7-drimethoxyflavone), 5, 7, 4-trihydroxy-8-methoxy flavone (5, 7, 4-trihydroxy-8-methoxyflavone), oroxylin A-7-O-glucuronide (oroxylinA-7-O-glucuronide), 5, 7, 2-trihydroxy methoxy flavone (5, 7, 2-trihyroxy-6-methoxyflavone), 5, 2-dihydroxy-6, 7, 8-trimethoxy flavone (5, 2-dihydroxy-6, 7, 8-trimethoxyfla-vone), 5-gate of a lane base-7, 8-dimethoxy flavone (5-hydroxy-7, 8-dimethoxy-flavone), Norwogonin (norwogonin), dihydro baicalin (dihydro-baicalin), 5, 7, 2-trihydroxyflavone (5, 7, 2-trihydroxyflavone), 5, 7, 2-trihydroxy-8, 6-dimethoxy flavone (5, 7, 2-trihydroxy-8, 6-dimethoxyflavone), 5, 7, 2, 5-tetrahydroxy-8, 6-dimethoxy flavone and viscidulin Ⅲ (5, 7, 2, 5-tetrahydroxy-8, 6-dimethoxyflavone, vis-ciduiin III, 5, 2, 5-trihydroxy trimethoxy flavone (5, 2, 5-trihy-droxy-6, 7, 8-trimethoxyflavone), baicalin-7-O-β-D-glucopyanoside (baicalein-7-O-β-D-glucopyranoside), 5, 7, 2-trihydroxy-8-methoxy flavone (5, 7, 2-trhiyroxy-8-methoxyflavone), 5, 7, 2, 3-kaempferol (5, 7, 2, 3-trihydroxy-6-methoxyflavone), 5, 7, 2, the great base flavone (5 of 3-tetra-, 7, 2, 3-tetrahydroxyflavone), 3, 5, 7, 2, 5, 6-pentahydroxyflavone (3, 5, 7, 2, 5, 6-pentahydroxyflavone) be viscidulin Ⅰ (viscidulin I), (2S)-7, 2, 6-trihydroxy-5-methoxy flavanone ((2S)-7, 2, 6-trihydroxy-5-methoxyflavanone), 2, 6, 2, 4-tetrahydroxy-6-methoxyl group chalcone (2, 6, 2, 4-tetrahydroxy-6-methoxychalcone), 5, 7, 2, 5-kaempferol (5, 7, 2, 5-tetrahydroxyflavone), left-handed eriodictyol (eriodictyol), Herba Scutellariae Barbatae kind element (rivularin) and viscidulin Ⅲ-2-O-β-D-glucopyanoside (viscidulin III-2-O-β-D-glucoplyranoside) etc.In addition also containing cupreol (β-sitosterol), campesterol (campesterol) and stigmasterol (stigmasterol).
Pharmacological action:
1, antibacterial action: Radix Scutellariae decoct 100% concentration, flat band method test, to dysentery bacterium, bacillus typhi, Salmonella paratyphi, vibrio cholera, escherichia coli, Bacillus proteus, bacillus pyocyaneus, staphylococcus, hemolytic vessel used to hold grain at the imperial sacrifice coccus (a, B), Diplococcus pneumoniae, diphtheria corynebacteriumetc. there being inhibitory action.Radix Scutellariae decoct test tubemethod test 1:1280 concentration can suppress Bacillus typhi, hemolytic streptococcusa, 1:640 control of the concentration Hemolytic streptococcus B, diplococcus pneumoniaeand shigella flexneri, people tubercule bacillush37,1:320 concentration can suppress vibrio cholera, dysentery bacterium; During 1:80 concentration, sonne bacillus has inhibitory action, and Radix Scutellariae alcohol immersion 0.5g/ml or 0.05g/ml, uses agar slant culture, medicinal liquid with culture medium1:1 mixes, right bacillus pyocyaneushave inhibitory action, Radix Scutellariae alcohol immersion 2g/ml concentration, Plating test is to large intestine bacillus, fructus Citri tangerinae grassbacillus, staphylococcus aureusthere is inhibitory action, Radix Scutellariae decoct, alcohol extraction agent 1g/ml concentration, when testing by flat band method pair meningitiscoccus all has the effect of pressing down.
2, antifungic action: Radix Scutellariae decocting liquid, test tube slant method tests 4% control of the concentration Canis familiaris L. denticle born of the same parents bacterium and trichophyton, 8% control of the concentration xu Lanfamily name achorion, 10% control of the concentration oidium schoenleinii Mongolia mutation, 15% control of the concentration homocentricity trichophyton and rustcolor trichophyton, Radix Scutellariae water logging agent 1:3 concentration is right in vitro violettrichophyton, Trichophyton concentricunm, oidium schoenleinii, Microsporon audouini, Pilus Caprae seu Ovis sample microspore tinea bacterium, redness epidermistinea bacterium, K, W, family name epidermophyton, star nocardia etc. have in various degree antibacterialeffect.
3, antivirus action: Radix Scutellariae decoct 25-100% concentration, in vitro tests has copied inhibitory action to hepatitis B virus DNA.
4, antiinflammatory antiallergic action: Radix Scutellariae 70% ethanol extraction 200,500mg/kg gavage baicalin, baicalin, wogonin 50,100mg/kg gavage, can suppress acetic acidthe mouse peritoneal caused oozes out increase, to 48/80(compound title, Sigma produces) rat that causes foot is swollen also has inhibitory action, and Radix Scutellariae 70% ethanol extraction 500mg/kg gavage, baicalin, baicalin and wogonin 100mg/kg gavage are to rat adjuvant arthritishave inhibitory action, Radix Scutellariae water extract 100,200mg/kg gavage, to rat passive cutaneous anaphylaxis, PCA(PCA) inhibitory action is had, but right chloropicrincause micecontact dermatitis(ear swelling) has no significant effect.
5, to the effect of central nervous system: Radix Scutellariae decoct 4g/kg lumbar injection, defensive to mice trained reflexpositive Reflection delay can be made long, and right unconditioned reflexand differentiation is without impact, illustrates that Radix Scutellariae can strengthen cortex process of inhibition, Radix Scutellariae decoct 2g/kg, has refrigeration function to typhoid fever mixed vaccine pyrogenicity rabbit, but also have report Radix Scutellariae water decoction or a Liquor infusion 5-9g/ gavage, or 2g/ only, all can not prove Radix Scutellariae pair antityphoid vaccinepyrogenicity rabbit has refrigeration function.
6, to cardiovascular effect: Radix Scutellariae alcohol extract 1g/kg intravenous injection, anaesthetized dog blood pressure can be made to decline.Radix Scutellariae decoct 0.06g/kg intravenous injection, has obvious hypotensive effect to anesthetized dog, baicalin 20mg/kg intravenous injection, can make anaesthetized dog blood pressure decline 40-50%, Radix Scutellariae preserved material gavage/kg gavage, 3 times/day, continuous 4 weeks, makes chronic renal hypertension dog blood pressure drops, heart rateslack-off.Baicalin 2 × 10(-4) mol/l, at all competitive antagonism of guinea pig in vitro aortic article, pulmonary artery bar, tracheal strip and right atrium epinephrine, norepinephrine and dopaminethe contraction caused, also antagonism isoproterenoldiastole trachea and the effect of increase right atrium spontaneous frequency, prompting baicalin all has blocking effect to a, B1, B2 receptor.
7, antiplatelet aggregation and anticoagulant: baicalin, wogonin, oroxylin A, skullcapflavone II and chrysin (chrysin) are when concentration 1.0mM, all can suppress collagen-induced rat platelet aggregation, chrysin also has inhibitory action to the platelet aggregation that ADP induces, baicalin and the platelet aggregation of wogonin to arachidonic acid-induction also have inhibitory action, and baicalin and baicalin are that fibrin also suppresses to the change fibrinogen of thrombin induction; Baicalin and baicalin 20,50mg/kg gavage, the rat of induced by endotoxin induction disseminated inravascular coagulation, the reduction of platelet and fibrinogen content can be prevented.
8, blood fat reducing: Radix Scutellariae infusion 10%2ml/ gavage, successive administration 7 weeks, the rabbit anteserum cholesterol level of cholesterol feed can be made to decline, and baicalin, baicalin 100mg/kg gavage, can reduce experimental hyperlipidemiarat Semen Maydis oil-cholesterol- cholic acidthe content of feed serum free fatty acid, triglyceride and liver triglyceride, skullcapflavone II 100mg/kg gavage, can reduce the content of serum total cholesterol and liver triglyceride, increases the content of Serum High-Density Lipoprotein-Cholesterol (HDL-ch), wogonin100mg/kg gavage, the deposition of liver triglyceride can be prevented and increase the content of serum hdl-ch, baicalin, baicalin 100mg/kg gavage, to the hyperlipemia rat that ethanol causes, liver T-CHOL, free cholesterol and content of triglyceride can be reduced, wogonin can reduce the level of serum triglycerides, and baicalin can increase serum hdl-ch content.
9, protect the liver, function of gallbladder promoting, antioxidation: Radix Scutellariae methanolic extract 1000mg/kg lumbar injection, the rats'liver caused α-naphthyl isothiocyanate (ANIT) infringement has inhibitory action, can suppress serum bilirubinincrease, Radix Scutellariae ethanol extract 50,100mg/kg, baicalin 50,100mg/kg gavage, has choleretic effect to rabbit, wogonin10(-4)-10(-6) in vitro tests of mol/l concentration, to rats'liver foundation of microsomal Lipid Peroxidationthere is inhibitory action, make malonaldehyde(MDA) content declines.Baicalin and baicalin 2.5 × 10(-4) mol/l, 1.0 × 10(-4) mol/l, wogonin 2.5 × 10(-4) mol/l, skullcapflavone II 2.5 × 10(-4) mol/l, wogonin-7-O-D glucuronic acid 2.5 × 10(-4) mol/l, 1.0 × 10(-4) mol/l, there is inhibitory action to the rat liver homogenate lipid peroxidation of FeC12-vitamin C-ADP mixture induction, the formation of liver MDA is significantly declined, the lipid peroxidation that NADPH mono-ADP causes also is suppressed.
10, anticancer: Radix Scutellariae ether extract is to mice leukemial1210 cell has cytotoxicity, and median effective dose is 10.4mg/ml, and the median effective dose of skullcapflavone II pair of mice L1210 cell is 1.5 μ g/ml, and baicalin, baicalin and wogonin are not remarkable to L1210 effect.
11, other effect: baicalin 10,20mg/kg intravenous injection, has diuresis to anesthetized dog.
Radix Glycyrrhizae is the dry root welding technology of glycyrrhizic legume GlycyrrhizauralensisFisch., Glycyrrhiza inflata Bat. GlycyrrhizainflataBat. or Glycyrrhiza glabra L. GlycyrrhizaglabraL., and the property of medicine is sweet, flat, GUIXIN, lung, spleen, stomach warp, effect is invigorating the spleen and replenishing QI, heat-clearing and toxic substances removing, expelling phlegm for arresting cough, relieving spasm to stop pain, coordinating the actions of various ingredients in a prescription, for weakness of the spleen and stomach, fatigue and weakness, shortness of breath and palpitation, cough with copious phlegm, the anxious pain of gastral cavity abdomen, extremity contraction, carbuncle sore tumefacting virus, cushion toxicity, strong.
Modern study: Radix Glycyrrhizae contains number of chemical composition, main component have glycyrrhizic acid, liquiritindeng, the chemical composition of Radix Glycyrrhizae is very complicated, and from Radix Glycyrrhizae, isolated compound has so far glycyrrhizin, enoxolone, liquiritin, isoliquiritin, neoliquriitin, neoisoliquiritin, glycyrrhizin, isoliquiritigenin and licoricidin (+)-Licoricidin., glycyrol, isoglycyrol, 7-methylcoumarin essence, umbelliferoneetc. tens of kinds of compounds, but these compositions and quantity usually can be different with the difference of the factors such as the kind of Radix Glycyrrhizae, planting area, collecting time, and large quantifier elimination shows, glycyrrhizin and flavonoid substancesbe most important biological active substances in Radix Glycyrrhizae, be mainly present in the part within licorice epidermis.
1, to the effect of digestive system:
1.1 antiulcer actions: the main constituent glycyrrhizin of Radix Glycyrrhizae also has significant protective effect to the Rat Experimental ulcer formed by histamine and pylorus ligation.After it is reported, glycyrrhizin obviously can reduce rat pylorus and block the ulcer rates caused, but not only instead has increase trend without minimizing to gastric secretion.Also find that Radix Glycyrrhizae extractum etc. is to rat ligation pylorus in zoopery treatment, the ulcer that dog is formed by histamine has obvious inhibitory action.The methanolic extract Fml00 etc. of liquiritigenin, Isoliquiritigenin and licorice has obvious inhibitory action to zoopery ulcer.The rat of enoxolone to pylorus ligation has good antiulcer action, and its therapeutic index is higher.
1.2 impacts on gastric acid secretion: Radix Glycyrrhizae fluidextract gavage directly can adsorb gastric acid, rat is had to reduce gastric acid to normal dogs and Experimental oral ulcer, Fml00 intraduodenal administration is to the rat of acute and chronic gastritis flaccidity and pylorus ligation, the gastric secretion on basis can be suppressed, share aobvious synergism with paeoniflorin, Fml00 has remarkable inhibitory action to the gastric secretion that peptone, histamine and Carbamoylcholine cause.
The spasmolysis of 1.3 pairs of gastrointestinal smooth muscles: use flavonoid glycosides contained by Radix Glycyrrhizae to rabbit clinically, the intestine in vitro of Cavia porcellus is inhibitory action, number of contractions is reduced, tensity reduces, and to barium chloride, in vitro intestinal smooth muscle spasm caused by histamine has spasmolysis, but glycyrrhizin, enoxolone is to smooth muscle then unrestraint effect, in addition, ammonium glycyrrhizinate and enoxolone oral absorption are also not good, Radix Glycyrrhizae decocting liquid, Radix Glycyrrhizae fluidextract, Fml00, glycyrrhizin, isoliquiritigenin etc., also obvious inhibitory action is had to intestine in vitro, if when intestinal tube is in spasticity, then there is obvious spasmolysis.
1.4 raise 7 same flavonoid glycoside and glycoside unit respectively from Radix Glycyrrhizae and Glycyrrhiza glabra L., the experiment proved that the effect all with spasmolytic and Canker-Resistance, to remove the glycyrrhiza preparation of glycyrrhizin or to extract the compounds such as its flavonoid for clinical, may be conducive to improving curative effect and reducing side effect, point significant from the methanolic extract of Glycyrrhiza glabra L..
1.5 hepatoprotective effects: Radix Glycyrrhizae fluidextract (0.2ml/10g) can reduce acetaminophen (AAP) (200mg/kg in advance mouse stomach, ip lumbar injection) fatality rate of poisoning mice, and have obvious protective effect to acetaminophen induced mice hepatic injury, mice is not the spinoff of hepatic necrosis to the liver glycogen decline effect of 2-3 after acetaminophen hour, and it is closely related with its toxic metabolite, Radix Glycyrrhizae can resist this effect, illustrate that its protective effect may be partly caused by the amount minimizing due to toxic metabolites, glycyrrhizin obviously can stop the rising of carbon tetrachloride poisoning rat glutamate pyruvate transaminase, the accumulation of triglyceride in liver can also be reduced, pathologic examination is visible, through glycyrrhizin, all comparatively matched group is light in its hepatic injury of rat of enoxolone treatment.Histochemical observation shows, the Rat Liver glycogen of enoxolone treatment obviously increases, the serum tire first globulin recall rate of glycyrrhizin and enoxolone is also higher than matched group, these two kinds of composition collagen-frees are pointed out to dissolve and re-absorbed effect, liver injury animals model P caused by carbon tetrachloride, glycyrrhizin, enoxolone is high inhibition effect to hepatic injury, enoxolone can also generate the generation of free radical and lipid peroxide by strong inhibition carbon tetrachloride, can Ca(2+ be suppressed) flow into primary cellular defect caused in cell, prompting enoxolone is in the inhibition of hepatic injury, antioxidation and suppression Ca(2+) flow into intracellular important role, glycyrrhizin may be present remarkable effect after hydrolysis in body.
1.6 impacts on bile secretion: glycyrrhizin can increase the bile secretion of biliary pore fistula rabbit, and glycyrrhizin 5mg/kg significantly can increase the bile secretion of rabbit, raise the red matter of gallbladder after rabbit ligation bile duct and have inhibitory action.
Certainly, its effective ingredient is not singly the side effect such as edema, blood pressure rising caused by glycyrrhizin and is restricted the clinical efficacy of 1.7 Radix Glycyrrhizae extractum, powder treatment Peptic Ulcers.
2, on the impact of cardiovascular system
2.1 antiarrhythmic effects: Radix Glycyrrhizae Preparata extracting solution (1ml is containing Chinese medicine 1g), rabbit occurs pressing 1g/kg intravenous injection after the 2 minutes by Aconitine Induced arrhythmia, matched group is to normal saline, result shows all to show significant differences to ectopic rhythm and sinus rhythm, show that Radix Glycyrrhizae Preparata has the Arrhythmia of obvious anti-Aconitine Induced, Radix Glycyrrhizae Preparata decoct perfusion Bufo siccus isolated heart, heart contraction amplitude can be made obviously to increase, glycyrrhizin has excitation to Isolated Toad Heart, this effect has obvious antagonism with acetylcholine and physostigmine etc., synergism obvious with epinephrine tool.
2.2 effect for reducing fat and anti-atherogenic stalk turn use into: glycyrrhizin has the effect of certain reduction blood cholesterol per capita to the hypertension that the experimental high-cholesterol disease of rabbit and cholesterol raise, glycyrrhizin 10mg/kg every day intramuscular injection, continuous 5 days, obvious effect for reducing fat is had to Experimental Rabbit hyperlipemia, plasma cholesterol matched group is 89 ± 4mg%, and administration group is 43 ± 4mg%; Plasma triglyceride matched group is 168 ± 10mg%, administration group is that the glycyrrhizin (2mg/ days) of 90 ± 4mg% low dose can make the cholesterol of Experimental Atherosclerotic Rabbits reduce within a certain period of time, atherosis degree alleviates, large artery trunks and crown atherosclerotic development within 20mg/ days, can be stoped, but when dosage is larger, (40mg/ days) is invalid on the contrary.The rabbit of glycyrrhetate (10mg/kg, oral) to hyperlipemia rat and experimental atherosclerosis has the effect of hypercholesterolemia, lipoprotein and beta lipoprotein triglyceride; Declining with the cholesterol in rat liver and beta lipoprotein content in Rabbit Aorta, the blood fat reducing of glycyrrhetate and study of anti-atherogenic effect stronger than polymerization Saponin.Experiment in vitro observes glycyrrhizin 1mM all can suppress 50% haemolysis to CP50 and AP50.Its inhibition site, can have the inhibition of 35% in system as seen in the A-Tee hydrolysis of Cis with same dosage, thus conclusion to be tired CH50 owing to inhibit Cis thus have impact on complement.Effect in AP is the reduction of C3, due to complementary reaction suppress by glycyrrhizin, the process reaction trend of relevant inflammation is alleviated and static, and lipid system and Hepatic function improvement, the pathogenesis of tremulous pulse disease is blocked.
The effect of 3 pairs of respiratory systems:
Radix Glycyrrhizae extractum and licorice mixture oral after can cover the pharyngeal mucosa of inflammation, relax inflammation to its stimulation, thus performance antitussive effect, enoxolone has obvious central antitussive effect, the two cholate of hydrogen succinate of enoxolone is oral, its antitussive effect is similar to codeine, enoxolone choline 501mg/kg can suppress Cavia porcellus to suck the coughing fit of 80% caused by ammonia, effect and codeine lmg/kg subcutaneous injection zero difference, heavy dose of enoxolone (1250mg/kg) can make mouse breathing suppress; The bronchospasm that enoxolone causes materials such as 5-hydroxy tryptamine; there is more weak protective effect; also obvious antitussive effect is had to the cough caused by electricity irritation cat superior laryngeal nerve; when with Radix Glycyrrhizae same dose level; hydrocortisone also shows antitussive effect; but dose-effect curve is different from Radix Glycyrrhizae; and the cough caused Cats superior laryngeal nerve is invalid; therefore think that Radix Glycyrrhizae antitussive effect and antiinflammatory are had nothing to do but to be produced by maincenter; Radix Glycyrrhizae can also promote throat and bronchial secretion; make the easy expectoration of expectorant, present eliminating phlegm and relieving cough effect.
4, on the impact of central nervous system
4.1. antiinflammatory action: Radix Glycyrrhizae has the antiinflammatory action of Phenylbutazone or hydrocortisone sample, its anti-inflammatory component is glycyrrhizin and enoxolone, enoxolone is to the granuloma induced by implantation of cotton pellets of rat, formaldehyde swelling of the feet subcutaneous granuloma inflammation etc. all has inhibitory action, its antiinflammatory is tired and is about 1/10 of cortisone or hydrocortisone, Rat Carrageenan colloidality swelling of the feet and antiinflammatory are tired, with hydrocortisone for 1, then glycyrrhizin, enoxolone is respectively 0.14 and 0.03, glycyrrhizin have the effect suppressing granulation to be formed, go out to have inhibition to the typical tuberculin reaction of delayed-type hypersensitivity, glycyrrhizin and enoxolone, to inflammatory reaction I, II, there was inhibitory action III phase, mouse mainline glycyrrhizin 25, 50mg/kg, the passive cutaneous anaphylaxis, PCA that obvious suppression Radix Trichosanthis causes, liquiritin has suppression mice carrageenin edema and suppresses the effect of sensitive cells release chemical transmitter substance.Radix Glycyrrhizae antiinflammatory action may with suppress blood capillary permeability-related, or relevant with adrenal cortex, also have and think, Radix Glycyrrhizae have impact on intracellular biological oxidizing process, reduces cell to the reactivity stimulated and creates antiinflammatory action.
Radix Platycodonis is the dry root of Campanulaceae Radix Platycodonis Platycodongrandiflorum (Jacq.) A.DC., the property of medicine for bitter, pungent, put down and return lung meridian, effect is lung qi dispersing, sore-throat relieving, eliminate the phlegm, evacuation of pus, for cough with copious phlegm, uncomfortable in chest not smooth, pharyngalgia hoarseness, lung abscess vomiting pus.
Modern study: root is containing multiple Saponin, and got 18 kinds of triterpenoid saponin so far, they are, kikyosaponin (platycodin) A, C, D, D2, D3, remove celery glycosyl kikyosaponin (deapioplatycodin) D, D3, 2-O-=acetyl group kikyosaponin (2-O-acetylplatycodin) D2, 3-O-acetyl group kikyosaponin (3-O-acetylplaty-codin) D2, polygalin (polyglalacin) D, D2, 2-O-acetyl group polygalin (2-O-acetylpolygalacin) D, D2, 3-O-acetyl group polygalin (3-O-acetylpolygalacin) D, D2, Radix Platycodonis glycoside acid-A methyl ester (methylplatyconate-A), 2-O-methyl Radix Platycodonis glycoside acid-A methyl ester (methyl-2-O-methyplatyconate-A), Radix Platycodonis glycoside acid-A lactone (platyconicacid-Alactone), wherein main constituent is platycodin D, Platycodin A C D is called again 2-O-acetyl group platycodin D, platycodoside C is called again 3-O-acetyl group platycodin D.The ruscogenin that multiple mixing Saponin produces through complete hydrolysis has: platycodigenin (platycodigenin), Polygalacic acid (polygalacicacid), and a small amount of platycogenic acid (platycodigenin), Polygalacic acid (polygalacicacid), and a small amount of platycogenic acid (platycogenicacid) A, B, C; Enter as mixed Saponin row portiondivide hydrolysis, then obtain 8 kinds Saponins (pros-aponin), they in separation process with methyl ester shape or get: 3-O-β-D-glucopyranosyl Polygalacic acid methyl ester (methyl3-O-β-D-glucpyranosylpolygala-cate, 3-O-β-3-O-beta-D-Glucopyranosyl-D-glucose base Polygalacic acid methyl ester (methyl3-O-β-laminaribiosylpolygalacate), 3-O-β-D-glucopyranosyl platycodigenin methyl ester (3-O-β-D=glucopyranosylplatycodigeninmethylester) 3-O-β-gentiobiose base platycodigenin methyl ester (3-O-β-gluctinobiosylplatycodi-geninmethylester), 3-O-β-D-glucopyranosyl platycogenic acid A lactone methyl ester (3-O-β-D-glucopyranosylplatycogeninAlactonemethylester), 3-O-β-D-glucopyranosyl platycogenic acid A dimethyl ester (dimethyl3-O-β-D-glu-copyranosylplatycogenateA), 2-O-methyl-3-O-β-D-glucopyranosyl platycogenic acid A dimethyl ester (dimethyl2-O-methyl-3-O-methyl-3-O-D-glucopyranosylplatyc ogenateA). root is also containing betulin (betulin), α-Herba Spinaciae dish sterol (α-spinasterol), hitodesterol-β-D-Glucose glycoside (α-spinasteryl-β-D-gluco-side).
1, eliminate the phlegm and antitussive effect anesthetized dog oral this product decoct 1g/kg, can show the secretory volume increasing respiratory mucus, its intensity can compared with ammonium chloride.Also have obvious phlegm-dispelling functions to anesthetized cat, have the phlegm-dispelling functions of report kikyosaponin to be better than Radix Polygalae, inferior to senea (PoygalasenegaL.), the phenol red method result of the test of mice is then weaker than Radix Polygalae.When Saponin is oral contained by Radix Platycodonis, stimulation is to a certain degree caused to pharyngolaryngeal mucosa and gastric mucosa, cause respiratory mucosa hypersecretion reflectingly, sputum is diluted, impel it to discharge, rough kikyosaponin has antitussive effect, and guinea pig intraperitoneal injection and antitussive median effective dose are 6.4mg/kg.
2, hypoglycemic activity rabbit gavage Radix Platycodonis water or alcohol extract 200mg/kg can make blood glucose decline, the blood sugar lowering curve of water extract is similar to gavage 25 ~ 50mg/kg tolbutamide, water and alcohol extract 500mg/kg continuous 4 days gavages, also hypoglycemic activity is had to experimental alloxan diabetes rabbit, the hepatic glycogen reduced also is shown in recovery after medication, and food blood glucose can be suppressed to rise, comparatively water extract is strong in the effect of alcohol extract.
3, the thick kikyosaponin of antiinflammatory action has antiinflammatory action, the dosage gavaging 1/10 ~ 1/5 median lethal dose(LD 50) all has antiphlogistic effects to rat hindlimb chondrus ocellatus Holmes colloidality swelling of the feet and acetic acid swelling, gavage is less than the dosage of 1/10 median lethal dose(LD 50), every day 1 time, successive administration, swell also to have to rat granuloma and show inhibitory action, and it is also effective to rat assist agent arthritis, this kind of preparation can also reduce anaphylaxis, the capillary permeability of mice, the mouse writhing reaction that lumbar injection kikyosaponin causes and Abdominal effusion, the same Saponin of gavage can produce suppression, Radix Platycodonis is without direct antibacterial action, but its water extract can strengthen macrophage phagocytic function, strengthen the sterilizing power of neutrophilic leukocyte, improve the activity of lysozyme.
4, to the effect rat of blood circulation with rough kikyosaponin intravenous injection, visible temporary blood pressure drops, decreased heart rate and respiration inhibition, to isolated guinea pig auricle, it is negative inotropic action during high concentration, anesthetized dog tremulous pulse injects the thick kikyosaponin of 200 ~ 800mg/kg, the resistance of coronary artery and Buddhist nun's limb blood vessel can be reduced, increase blood flow, its intensity can compared with papaverine, also can increase coronary artery and hind limb blood flow amount when 4mg/kg intravenous injection, and with temporary hypotension, it is believed that this vasodilation is the direct effect of human peripheral blood pipe.
5, suppress gastric secretion and the rough kikyosaponin of antiulcer action to have when the dosage lower than 1/5 median lethal dose(LD 50) and suppress rat gastric secretion and anti-peptic ulcer effect, during 100mg/kg dosage, almost can suppress the gastric secretion caused by rat pylorus ligation completely, rat preduodenal injects the rough kikyosaponin of 25mg/kg, can prevent peptic ulcer from being formed, its effect is suitable with subcutaneous injection 10mg/kg atropine, but 100mg/kg gavage compares subcutaneous injection to the preventive effect of irritability ulcer atropinethe weak twice of 10mg/kg, to the Ulcer Models caused by rat acetic acid, rough kikyosaponin can make ulcer coefficient obviously reduce, and every day 25mg/kg group curative effect be high than Radix Glycyrrhizae extract FM100 200mg/kg every day group.
6, other acts on thick kikyosaponin calmness, analgesia and refrigeration function, mice voluntary activity can be suppressed, extend the length of one's sleep of ciclobarbital soluble, but to electric shock and the effect of pentetrazole convulsions unprotect, kikyosaponin can reduce the content of rats'liver inner cholesterol, increase the excretion of cholesterol and cholic acid, also have anti-acetylcholine and antihistamine effect, the isolated guinea pig ileum that acetylcholine and histamine can be suppressed to cause shrinks, rat oral gavage Radix Platycodonis 2g/kg, suppression and diuresis is had to the congested edema that Bilateral Cervical vein ligation causes, in vitro tests shows, this product decoct 1:10 has inhibitory action to acrothesium floccosum, edge anti-tumor activity is had to rat watt gram Z56 intramuscular injection tumor system (SWA16) during betulinol 400mg/kg contained by this product.
7, toxicity
Kikyosaponin has haemolysis, injection can not be used for, destroy in digestive tract hydrolysis after oral, namely without haemolysis, to mouse subcutaneous injection, minimum lethal dose is 770mg/kg, the median lethal dose(LD 50) of mouse stomach Radix Platycodonis decoct is 24g/kg, rabbit gavage this product decoct 40/kg, in 24 hours, 5 rabbits are all dead, when dosage is 20/kg, then all survive, kikyosaponin has very strong haemolysis, its hemolytic index and the place of production, source and growth year, acquisition time, processing method etc. and different, from 1:100 to 1:1000 not etc., the haemolysis of phloem is 4.4 ~ 6.5 times of the core of nature, unpeeled Radix Platycodonis haemolysis is slightly larger than peeling Radix Platycodonis, therefore Radix Platycodonis can not drug administration by injection, the minimum lethal dose of mouse subcutaneous injection is 770mg/kg, the median lethal dose(LD 50) of thick kikyosaponin gavage Mouse and rat is respectively 420mg/kg and people in 800mg/kg, subcutaneous injection is respectively 22.3mg/kg and 14.1mg/kg, the heavy dose of kikyosaponin of gavage, can reflex excitation vomiting center, can cause nausea, vomiting.
Radix Bupleuri is the dry root of umbelliferae bupleurum BupleurumchinenseD or Radix Bupeuri Scorzonerfolii. BupleurumscorzonerifoliumWilld., different by character, practises title " Radix Bupleuri " and " Radix Bupleuri Scorzonerifolii " respectively.
The property of medicine: pungent, bitter, is slightly cold, and returns liver, gallbladder, lung meridian, effect: evacuate and bring down a fever, dispersing the stagnated live-QI to relieve the stagnation of QI, elevate a turnable ladder yang-energy, for cold, fever, and alternate attack of chill and fever, distending pain in the chest and hypochondrium, menoxenia, uterine prolapse, proctoptosis.
Modern study: its composition of Radix Bupleuri is mainly containing saikoside (saikosapoinsa, b, c, d tetra-kinds), sterol, volatile oil (bupleurumol, eugenol etc.), fatty acid (oleic acid, linoleic acid, Palmic acid, stearic acid etc.) and polysaccharide etc., also containing compositions such as flavone, polyhydric alcohol, coumarin and trace element.Saikosaponin a is contained in the root of bigleaf thorowax root and stem, c, d, I, content up to 3.8%, and is therefrom separated to 4 kinds of polyenynes compounds: bupleurotoxin, bupleuronol, acetylbupleurotoxin and bupleurynol, these compounds are to light, thermally labile, oxidizable, bupleurotoxin and acetylbupleurotoxin have severe toxicity, and their median lethal dose(LD 50) is respectively 3.03 mg/kg, 3.13 mg/kg, α-terpinol (α-Terpineol), linalool (Linalool), α-cubebene (α-Cubebene), trans-caryophyllene (Trans-caryophyllene), longifolene (Longi-folene), nootkatone (Nootkatone), six hydrogen farnesyl acetones (Hexahydrofarnesylacetone), hexadecylic acid (Hexade-canoicacid), valeric acid (Pentanicacid), caproic acid (Caproicacid), enanthic acid (Heptylicacid), sad (Caprylicacid), n-nonanoic acid (Pelargonicacid), 2-heptenoic acid (2-Heptenicacid), 2-octenoic acid (2-Octenicacid), 2-nonenoic acid (2-Nonenicacid), phenol (Phenol), o-methoxyphenol (O-Methoxyphenol), cresols (Methylphenol), ethylphenol (Ethylphenol), thymol (Thymol), γ-enanthic acid lactone (γ-Heptalactone), γ-sad lactone (γ-Decalac-tone), Ma Suoyi lactone (Messoialactone), vanillin acetate (Vanillinacetate) etc. also containing Saponin, as saikoside (Saikosaponin) a, b, c, d and saikoside unit (Saikogenin) E, F, G, longispinogenin (Longispinogenin). still containing organic acid, as oleic acid (Oleicacid), linolenic acid (Linolenicacid), Palmic acid (Palmiticacid), stearic acid (Stearicacid), carnaubic acid (Lignocericacid) and hitodesterol (α-Spinasterol), oxeye alcohol (Adonitol), stigmasterol (Stigmasterol), bupleurumol (Bupleurumol), the alcohols materials such as adonite (Adonitol). in addition, also containing Radix Angelicae Dahuricae element (Ange-licin). Radix Bupeuri Scorzonerfolii. root is containing Saponin, fatty oil, volatile oil, bupleurumol, oxeye alcohol, hitodesterol. herb is also containing Quercetin, isoquercitin, rutin, narcissin etc.
1, to the effect of central nervous system:
1.1, anticonvulsant action: the suitable crude drug of mice (10) gavage Radix Bupleuri decoct 20g()/kg, the caffeine of subcutaneous injection various dose after l hour, compared with matched group, in 15 minutes there is the number of animals of fainting from fear in each group, the median effective dose obtaining medication group and matched group is respectively 350(385.O-318.2) mg/kg and 250(302.5-206.6) mg/kg, show that Radix Bupleuri decoct has antagonism to mice caffeine convulsions.
1.2, antipyretic effect: to rat (often organizing 6) lumbar injection Radix Bupleuri oil 300mg/kg(1/4 median lethal dose(LD 50)), Radix Bupleuri Total saponin 380 and 635mg/kg(1/5 and 1/3 median lethal dose(LD 50)), result shows, obvious refrigeration function is all had in 5-8 hour after injection yeast, adopt electric shock Mus tail method, Radix Bupleuri Total saponin 478mg/kg(1/4 median lethal dose(LD 50)) there is obvious analgesic activity, the suitable crude drug of mouse stomach Radix Bupleuri decoct 10g()/kg also has analgesic activity, its analgesic activity can break atropine gavage 25mg/kg or Allylnoroxymorphone subcutaneous injection 0.26mg/kg partial agonist.
1.3, sedation: bupleurum preparation and total saikosaponins all have obvious sedation, can sedation be there is in the thick saikoside 200-800mg/kg of Mouse oral, climb in test mice, thick saikoside has the sedation similar to miltown, oral motion 50 3nhibitory dose (CD50) is 347mg/kg, thick Saponin all has obvious suppression to the conditioned avoidance of rat, escape reaction, and Mouse oral total saikosaponins 500mg/kg can extend the length of one's sleep of ciclobarbital soluble.
1.4, antiinflammatory action: rat muscle injection 50mg/kg, 25mg/kg2% total saikosaponins aqueous solution, obviously can suppress the sufficient edema caused by dextran (6% solution 0.1ml/ only), inhibitory action is relevant to dosage, after rat goes both sides adrenal gland, inhibitory action obviously weakens, 2% aqueous solution of mouse peritoneal injection l00mg/kg Total saponin and 0.6% acetic acid 0.2ml/ are only, oozing out of the mouse peritoneal liquid that Dichlorodiphenyl Acetate causes has obvious inhibitory action, and caused by total saikosaponins and volatile oil lumbar injection on Carrageenan, rat foot is swollen all obvious inhibitory action.The mice foot that the oral 600mg of thick saikoside can also suppress 5-hydroxy tryptamine and Oleum Tiglii to cause is swollen.Vascular permeability that thick saikoside Dichlorodiphenyl Acetate, histamine and 5-hydroxy tryptamine cause increases inhibited, Saikosaponin a and d intramuscular injection or orally all have exudation and anti-granuloma effect.After Saikosaponin a and d lumbar injection, rat plasma corticosterone rolls up, and its adrenal gland's weight also has to be increased in various degree, possible antiinflammatory action with stimulate adrenal gland, promote that interrenal system is relevant.
2, on the impact of cardiovascular system:
Radix Bupleuri alcohol extract can make anesthetized rabbit blood pressure slightly decline, and total saikosaponins can cause of short duration nerve depressor response to dog, decreased heart rate; Also hypotensive effect is had to rabbit, isolated frog heart and guinea pig in vitro auricle test visible total saikosaponins 1-2 × 10(-4) concentration has suppression Myocardial Effects, thick Saponin has obvious haemolysis, the haemolysis intensity of saikoside is Saikosaponin d > a > c, but its haemolysis can by adenine, creatinine suppress, during the thick Saponin 5mg/kg of dog intravenous injection, can occur that temporary blood pressure drops and heart rate reduce, Radix Bupleuri aerial parts contains 6-8% flavonoid, has enhancing capillary action.
3, to the effect of digestive system:
3.1, effect to liver: the water logging agent of Radix Bupleuri and decoct (1:20) all can make total bile output of dog and bile salt component increase, thick saikoside oral 500mg/kg every day for three days on end, the liver function recovery of carbon tetrachloride hepatic injury rat can be made normal, the liver function caused by galactose and tissue injury can also be made to recover, the mouse liver injury experiment that Saikosaponin a causes carbon tetrachloride, visible peroxidating matter content reduces, in liver, GSH content raises, and GTP content declines in serum, in liver, content of triglyceride reduces, show there is protection hepatocyte injury and promote lipid metabolism in liver.
3.2, to stomach, duodenal effect: total saikosaponins concentration is at l-2 × 10(-4) time, the excited in vitro intestinal smooth muscle of energy, and not by atropine is resisted, at 3 × 10(-6) concentration time can strengthen in vitro intestinal Mus small intestinal the contraction that acetylcholine causes, the secretion of oral total saikosaponins energy gastric acid inhibitory, increase the pH value of gastric juice, to the acetic acid ulcer of Rat Experimental, every day oral thick Saponin 10mg/kg, continuous 15 days, there is the therapeutical effect promoting gastric ulcer, but larger dose 50 or 100mg/kg occur that ulcer worsens tendency on the contrary, with in stress ulcer caused by fixing immersion method, oral thick Saponin 500mg/kg has obvious inhibitory action, in addition, total saikosaponins has stronger inhibitory action to trypsin.
4. antipathogen effect:
Radix Bupleuri has antipathogen effect: Radix Bupleuri injection and the grease infected by influenza distilled out thereof have strong inhibition effect, the experiment in vitro of Saikosaponin a shows that infected by influenza also has inhibitory action, Radix Bupleuri also has anti-tubercle bacillus effect, injection of Radix Bupleuri also can treat herpes simplex virus keratitis, ulcer healing can be promoted, rear layer fold and essential layer are invaded profit edema and are disappeared, and contribute to recovering vision.
5, on the impact of substance metabolism:
5.1, on proteometabolic impact: Markets Drug mixture (3:2:2) obviously can increase the Protein synthesis of rat, and intramuscular injection total saikosaponins also has this effect.
5.2, on glycometabolic impact: total saikosaponins can make glycogen without obvious increase, promote that the utilization rate of glucose in TL and cholesterol biosynthesis obviously increases.
5.3, on the impact of lipid metabolism: total saikosaponins can suppress the steatolysis effect in the fat storehouse of epinephrine and ACTH induction, also suppress insulin to promote the nucleus formation of fat, fat mass in blood is reduced.
5.4, contained in Radix Bupleuri a-chondrillasterol has the effect reducing plasma cholesterol, can resist the effect that deracil reduces rabbit basal metabolism.
6, on the impact of hypophysis one adrenal cortex action function:
Oral Radix Bupleuri or saikoside can make mice or rat chest gland atrophy and adrenal gland's weight increase, wherein Saponin a and d can make adrenal gland obviously loose, and Saponin c effect is not obvious, Saikosaponin a or d can secrete ACTH by excited antepituitary, stimulate adrenal gland to cause synthesis and the secretion of corticosterone.
7, the effect of anti peroxidation of lipid:
The external impact on rabbit plasma MDA, plasma-free hemoglobin (PHb) after mouse liver even slurry two dialdehyde (MDA) and H2O2 effect of injection of Radix Bupleuri (1g/1ml), experimental result shows, blood plasma MDA, PHb that injection of Radix Bupleuri can obviously suppress the generation of liver homogenate MDA and H2O2 to cause raise, inhibitory action increases with dosage and strengthens, and shows the effect with anti peroxidation of lipid.
8, antitumor action:
Saikosaponin d gavage or lumbar injection have Tumor suppression growth to mice ehrlich carcinoma, and obviously can extend the life span of animal, with Radix Bupleuri with new westblue purebred white rabbit preparation has the tumor necrosis factor (TNF) of anticarcinogenic effect, and using hepatoma carcinoma cell as target cell, result makes cancer cellular necrosis, cracking; Do same experiment with Hela cell and lung glandular cell, also obtain identical result.
9, other effect:
9.1, immunization: mouse peritoneal injection Bupleurum chinense polysaccharide (molecular weight 9900) can significantly increase spleen coefficient, peritoneal macrophage phagocytic percentage and phagocytic index and influenza virus Serum Antibody titre, but do not affect splenocyte secretion hemolysin, Bupleurum chinense polysaccharide to normal mouse delayed hypersensitive reaction (DTH) without effect, but can completely and part recover cyclophosphamide or influenza virus to the suppression of mouse DTH reaction.Bupleurum chinense polysaccharide significantly improves the Splenic vein hemodynamics rate and natural of ConA activation kill and woundthe activity of cell, shows that Bupleurum chinense polysaccharide can improve mice body fluid and cellular immune function, and makes immunosuppressive condition have recovery to a certain degree.
9.2, Bupleurum chinense polysaccharide also has radiation resistance.
Instant component uses Cortex Mori, the Rhizoma Anemarrhenae, Semen Armeniacae Amarum, Gypsum Fibrosum, Fructus Forsythiae, Radix Glycyrrhizae, Radix Scutellariae, Radix Platycodonis, Radix Bupleuri science, reasonable compatibility, support mutually, be effective to treatment livestock and poultry respiratory sick, good effect, drug safety, and obtain sufficient proof through test, related tests data is as follows:
Four, clinical trial of the present invention
1, materials and methods
1.1, test material
Composition of medicine of the Chinese herbal medicament oral liquid of a kind of livestock and birds respiratory disease of the present invention and preparation method thereof.
1.2, test poultry to select and grouping
Test A is arranged in 3 closed hen houses that certain chicken house is in the different onset stage, adopt pathological material of disease, blood sample cuts open inspection through AGP, HI test, antibacterial culturing, virus purification be diagnosed as respiratory tract disease in conjunction with clinical symptoms, pathology, first 2015, completely random is divided into test group 1007, matched group 1006; Second 2024 completely randoms are divided into test group 1012, matched group 1012; Third 2016, completely random is divided into test group 2008, matched group 2008.3 are the brown commercial generation laying hen of Luo Man in 28 week age for examination chicken, and a first chicken group is morbidity the 3rd age in days, and symptom (being in incubation period) not yet appears in a second chicken group, and third chicken group is the 14th age in days after morbidity.
Another test B is arranged in 3 confined swine housing that certain pig farm is in the different onset stage, adopt pathological material of disease, blood sample cuts open inspection through AGP, HI test, antibacterial culturing, virus purification be diagnosed as respiratory tract disease in conjunction with clinical symptoms, pathology, first 206, completely random is divided into test group 105, matched group 101; Second 212 completely randoms are divided into test group 106, matched group 106; Third 203, completely random is divided into test group 102, matched group 101, and 3 are pig in 5 week age for examination pig, and a first swinery is morbidity the 5th age in days, and symptom (being in incubation period) not yet appears in a second swinery, and third swinery is the 12nd age in days after morbidity.
1.3, feeding and management
Every house carries out feeding and management by normal feeding and management way, and each feeding and management condition is identical, and each test group its corresponding matched group management method is also just the same.
1.4,1 testing program A group
The enrofloxacin drinking-water of each matched group 160mg/L, test group Chinese herbal medicament oral liquid is drunk water, a test first dosage is 200mg/L, test second, third group of dosage are 160mg/L, continuous use 14d, observe every day and record each group of chicken spirit, search for food, drink water, feces, egg number, the situation such as morbidity number and death toll, in this test, a second chicken group test the 4th day two groups all start morbidity, the recurrence in the 20th day behind the 6th day of test i.e. onset of the matched group of third chicken group.
1.4,2 testing program B groups
The enrofloxacin drinking-water of each matched group 160mg/L, test group Chinese herbal medicament oral liquid is drunk water, a test first dosage is 200mg/L, test second, third group of dosage are 160mg/L, continuous use 14d, observe every day and record each group of chicken spirit, search for food, drink water, feces, egg number, the situation such as morbidity number and death toll, in this test, a second swinery test the 7th day two groups all start morbidity, the recurrence in the 17th day behind the 8th day of test i.e. onset of the matched group of third swinery.
2, results and analysis
2.1, results and analysis A group
Result of the test is shown in table 1as can be seen from the test results, during on-test, each test group and matched group laying rate are on close level (P>0.05), in-test, each test group is obviously better than corresponding matched group in all indexs, and each test group compares with corresponding matched group, and on sickness rate, a first performance is identical, second performance significant difference (P<0.05), third performance pole significant difference (P<0.01); On mortality rate, first, second two performance difference is not significantly (P>0.05), and third performance difference extremely significantly (P<0.01); In laying rate fall, first, second, the third 3 performance differences are all extremely significantly (P<0.01); In deformity (soft-shelled egg etc.) egg rate, first, second, the third 3 performance differences are all significantly (P<0.05).
table 1result of the test
2.2, results and analysis B group
Result of the test is shown in table 2as can be seen from the test results, during on-test, each test group and matched group cure rate are on close level (P>0.05), in-test, each test group is obviously better than corresponding matched group in all indexs, and each test group compares with corresponding matched group, and on cure rate, a first performance is identical, second performance significant difference (P<0.05), third performance pole significant difference (P<0.01); On mortality rate, first, second two performance difference is not significantly (P>0.05), and third performance difference extremely significantly (P<0.01); In cure rate fall, first, second, the third 3 performance differences are all extremely significantly (P<0.01)
table 2result of the test
3, conclusion
By the result of this controlling experiment in conjunction with the epidemic characteristic of primary disease in locality, these points conclusion can be drawn:
(1) before, during and after respiratory tract infection sense morbidity, 3 stages apply Chinese herbal medicament oral liquid elements addition of the present invention, all greatly can reduce the mortality rate of poultry and the amplitude of laying rate decline, Chinese herbal medicament oral liquid has obvious antiviral, anti-inflammatory effect; Obviously be better than enrofloxacin.
(2) the resistance to poultry group excessively of first attack obviously obtains certain immunity to this condition of disease, but because primary disease destroys pig immune system, many poultry groups often have after onset 17d recurs primary disease to some extent, if add this Chinese herbal medicament oral liquid after onset effectively can prevent this palindromia.
(3) apply this Chinese herbal medicament oral liquid control primary disease and be obviously better than enrofloxacin in the decline of reduction laying rate, eggshell quality recovery and in reduction pig mortality rate.
The present invention obtains obvious curative effects in clinical practice, in order to be applied to clinical applicant better according to registration declaration material requirement in " new drug registration management way ", Mouse Acute Toxicity experiment is carried out to said preparation, result of the test illustrate this Chinese herbal medicament oral liquid and injection less to Mouse Acute Toxicity, larger dose application said preparation in clinical one day is pointed out to produce toxic reaction, lower to the long-term peroral administration toxicity of rat, safety is better.
Five, the Mouse Acute Toxicity research of Chinese herbal medicament oral liquid and injection
The present invention is in Chinese veterinarian's theoretical basis, and in conjunction with the achievement in research of modern Chinese medicine to swine diseases poison, refining pure Chinese medicinal preparation, has and act on fast, curative effect high.
The present invention obtains obvious curative effects in clinical practice, in order to be applied to clinical applicant better according to declaration material requirement in " novel chiral synthon Manufacture management way ", carries out Mouse Acute Toxicity experiment and rat long term toxicity test to said preparation.
1, test medicine is tested
Test sample is Chinese herbal medicament oral liquid and injection, by our company's development and production voluntarily, Clinical practice amount is 330mg/Kg, preparing test sample concentration with distilled water before experiment is 30% (this concentration is the Cmax that said preparation can complete mouse stomach operation), for experimental applications, it is mouse stomach.
2, laboratory animal
ICR strain SPF level mice, male and female totally 40, weight: 18 ~ 21.5g.Be purchased from Medical School of Zhengzhou University Experimental Animal Center, credit number SCXK (Henan) 2009-0001.After mice normally raises 3d, test.
3, experimental program
Trial test display said preparation can not determine median lethal dose(LD 50) (LD50), therefore, does maximum dosage-feeding and measures.
Experiment grouping: 40 mices are divided into matched group and administration group at random, often organize each 10 of male (♂), female (♀), control group administered physiological saline 0.4ml/10g, 3 times/d; Administration group to test sample 300g/ (kgd) (30%, 0.4ml/10g), 3 times/d.
Administration and experiment condition: normally raise after administration, observe 2 weeks, the body weight of 1,2 week before the mice abnormal response after record administration and administration and after administration.Experimental situation (SPF animal housing) room temperature: (23 ± 1.0) DEG C; Humidity: (46 ± 3) %, mice empty stomach or half fasted conditions before administration, three delivery time: 1 ~ 2h.
table 1body weight is added up table (g)
4, experimental result
Control group mice is after gavage gives normal saline in 2 weeks, reaction without exception, administration group mice is after giving the test sample second day (20h) of Chinese herbal medicament oral liquid and injection, defecate is brown, shapeless, fecal pollution anus and crissum, play feces character on the 3rd day and comprise the recovery such as color, shape normally, until experiment terminates.
In whole experimental period, test sample group (administration group) mice of Chinese herbal medicament oral liquid and injection is except above-mentioned feces character changes, and have no other abnormal responses such as ingesting, drink water, be movable, matched group and administration group mice are all without death.
Wherein maximum dosage-feeding: 300g/kg/d (30%) Mice Body mass change is shown in table 1, increase comparatively matched group after administration group Mice Body mass delivery slow, but between matched group and administration group, male female respectively at the more equal no difference of science of statistics of the body mass ratio of each time point.
5, experiment conclusion
To be 500g/ (kgd) concentration be the test sample maximum dosage-feeding of Chinese herbal medicament oral liquid and injection 50% under heavy dose of administration, the rarely seen feces character caused comparatively greatly due to dosage of mice changes and weight increasess slowly, have no the overt toxicity reaction caused by said preparation, also without dead mouse.
This result of the test illustrates that Mouse Acute Toxicity of the present invention is less, points out larger dose application said preparation in clinical a day to produce toxic reaction.
Six, the present invention treats effect of livestock and birds respiratory disease
Effect of the present invention: there is stronger heat-clearing and toxic substances removing, strengthening vital QI to eliminate pathogenic factors, training spleen reinforcing kidney, benefiting QI and nourishing blood, broad-spectrum antiviral, antibacterial, body can be induced to produce interferon, enhancing antibody is formed, the immunity of enhancing body and each system repair ability of body, the function such as disease-resistant growth-promoting, anti-stress, especially to the avian influenza prevention best results of birds.
1) application of broad-spectrum antiviral: the present invention is a kind of antiviral and interferon inducers of wide spectrum, it can the function of stimulating expression of macrophage and T cell, and making E ring form cell number increases, and Cytokines Production promotes that interleukin induces.Thus make animal body produce endogenous interferon, thus reach antiviral object, be used for the treatment of the viral infectious such as livestock and birds respiratory disease.
2) application of vaccine immunity power is strengthened: the present invention itself has outside enhancing body name epidemic disease power; the immunity of vaccine Seedling is also made greatly to strengthen; and to vaccine Seedling, there is good protected effect; the serum that astragalus polysaccharides can strengthen Mareks disease vaccine according to research reports draws body to tire; after compound Radix Astragali polysaccharide granule and NDV, IV vaccine conbined usage can improve immunity, the Serum HI antibody of pig is tired; coordinating Chinese herbal medicament oral liquid and injection when using coccidial vaccine, pig immunity to coccidiosis protection can be strengthened.
3) to the effect of liver: the present invention can promote that hepatocyte DNA, RNA synthesize; alleviate the pathological changes that Hepatoxic substance causes; strengthen liver detoxification function; protective effect is had to hepatocyte; good prevention effect is all had to pork fat liver, hydropericardium hepatitis syndrome, large hep, hepatitis splenomegaly syndrome; can pig feed intake be improved simultaneously, thus impel the growth promoter of pig.
4) to renal effect: the present invention can improve nephrocyte metabolism and renal function, reduce serum creatinine level, renal failure after the nephrectomy can be alleviated.All there is good prevention effect to diseases such as nephrotic syndrome, acute renal failure, nephrotic syndrome, renomegaly urate deposition, strong kidney object can be played simultaneously, be conducive to the performance of pig growth reproduction function.
5) reproductive performance is improved: the present invention has stabilized cell, defying age, free radical resisting and snperoxiaized effect, long-term regularly use, service life and the service efficiency of boar can be significantly improved, in addition, Chinese herbal medicament oral liquid and injection have short gonad effect, can make that endometrial thickness, cavity of uterus expand, the weight of cornua uteri and ovary increases to jenny.Chinese herbal medicament oral liquid and injection can also improve the reproductive performance of buck, and spermatozoon activity, living spermatozoa percentage, sperm concentration etc. can be made to be significantly increased.
6) there is raising nutrient utilization, promote the function of growth of animal, the multiple nutrients materials such as Chinese herbal medicament oral liquid and the acid of injection embedded amine groups, vitamin, trace element, and UGF (UGF), the speed of growth of pig can be significantly improved as feed additive, promote Abwehrkraft des Koepers, improve pig Egg Quality and output.
In a word, the present invention has:
1) clinical prevention of the respiratory tract disease of Swine and the effective immune prevention and control for the treatment of and respiratory tract disease pig are used for the treatment of;
2) effectively treatment and treatment pig body immunologic hypofunction atrophy such as () thymus, liver, kidney, fabricius bursa;
3) slow to the poultry speed of growth, feed intake is low, regularity is poor, egg fowl subtracts egg and intractable watery diarrhea, proctoptosis etc. without lay eggs peak or unknown cause specially good effect;
4) this product has protection and synergism to vaccine, obviously promotes immunizing potency, can use with vaccine simultaneously;
5) this product and coccidiostat are used in conjunction and can significantly improve anticoccidial index;
6) the various viral disease of pig is treated, as porcine circovirus, reproductive and respiratory syndrome, influenza, pseudorabies, viral diarrhea, repeated relapsing asthma and innominate high fever etc.;
7) clinical application effect is good, and granule market is rare, more competitive than popular powder, and high in technological content, added value is large;
8) ultra micro spiral granular preparation technique, advantage is distinct, is convenient to preserve and clinical practice, more easily cuts market;
9) character is stablized, and water solublity is fabulous, nontoxic, harmless, no drug residue;
10) spice is evenly convenient, and product development has a extensive future;
Porcine respiratory disease of the present invention through studying for many years, clinical trial and to practice summary, determine that our prescription is feasible, effectively, be worthy to be popularized, be effective to the control of porcine respiratory disease, research success of the present invention will go out great economic benefit and far-reaching social benefit for social creativity with exploitation.

Claims (5)

1. treat a Chinese herbal medicine composition of medicine for livestock and poultry respiratory disease, it is characterized in that: described composition of medicine is made up of following proportioning raw materials: Cortex Mori 95-105g, the Rhizoma Anemarrhenae 75-85g, Semen Armeniacae Amarum 75-85g, Gypsum Fibrosum 110-130g, Fructus Forsythiae 55-65g, Radix Glycyrrhizae 55-65g, Radix Scutellariae 95-105g, Radix Platycodonis 55-65g and Radix Bupleuri 55-65g.
2. treat a preparation method for the Chinese herbal medicine composition of medicine of livestock and poultry respiratory disease, it is characterized in that: described composition of medicine is made up of following proportioning raw materials: Cortex Mori 95-105g, the Rhizoma Anemarrhenae 75-85g, Semen Armeniacae Amarum 75-85g, Gypsum Fibrosum 110-130g, Fructus Forsythiae 55-65g, Radix Glycyrrhizae 55-65g, Radix Scutellariae 95-105g, Radix Platycodonis 55-65g and Radix Bupleuri 55-65g; Described preparation method comprises the steps:
Step 1: selection: get the Cortex Mori of a certain amount of drying, the Rhizoma Anemarrhenae, Semen Armeniacae Amarum, Gypsum Fibrosum, Fructus Forsythiae, Radix Glycyrrhizae, Radix Scutellariae, Radix Platycodonis and Radix Bupleuri;
Step 2: soak: the mixture getting the water soaking Cortex Mori of 12 times of weight of dry medical material gross mass in step 1, the Rhizoma Anemarrhenae, Semen Armeniacae Amarum, Gypsum Fibrosum, Fructus Forsythiae, Radix Glycyrrhizae, Radix Scutellariae, Radix Platycodonis and Radix Bupleuri, soak time is 15-20min;
Step 3: first time lixiviate: by the mixture boiled after adding water in step 2, then the 25-35min that simmers in water;
Step 4: first time filters: the mixture obtained in step 3 is filtered, and collects first time filtrate;
Step 5: second time lixiviate: the filtering residue after step 4 being filtered boils after adding the water of 10 times of weight of dry medical material gross mass in step 1, then the 25-35min that simmers in water;
Step 6: second time is filtered: the mixture obtained in step 5 is filtered, and collect second time filtrate;
Step 7: third time lixiviate: the filtering residue after step 6 being filtered boils after adding the water of 10 times of weight of dry medical material gross mass in step 1, then the 15-25min that simmers in water;
Step 8: third time filters: the mixture obtained in step 7 is filtered, and collects third time filtrate;
Step 9: to merge, concentrated: the first time filtrate that step 4, step 6 and step 8 are obtained, second time filtrate and third time filtrate merge, and the mixed liquor after merging is concentrated into the concentrated solution of 1:1;
Step 10: storage: concentrated solution step 9 obtained collects storage at normal temperatures and pressures;
Treat a Chinese herbal medicine composition of medicine for livestock and poultry respiratory disease as claimed in claim 1, it is characterized in that: described composition of medicine is made up of following proportioning raw materials: Cortex Mori 95g, Rhizoma Anemarrhenae 75g, Semen Armeniacae Amarum 75g, Gypsum Fibrosum 110g, Fructus Forsythiae 55g, Radix Glycyrrhizae 55g, Radix Scutellariae 95g, Radix Platycodonis 55g and Radix Bupleuri 55g.
3. a kind of Chinese herbal medicine composition of medicine for the treatment of livestock and poultry respiratory disease as claimed in claim 1, is characterized in that: described composition of medicine is made up of following proportioning raw materials: Cortex Mori 100g, Rhizoma Anemarrhenae 80g, Semen Armeniacae Amarum 80g, Gypsum Fibrosum 120g, Fructus Forsythiae 60g, Radix Glycyrrhizae 60g, Radix Scutellariae 100g, Radix Platycodonis 60g and Radix Bupleuri 60g.
4. a kind of Chinese herbal medicine composition of medicine for the treatment of livestock and poultry respiratory disease as claimed in claim 1, is characterized in that: described composition of medicine is made up of following proportioning raw materials: Cortex Mori 105g, Rhizoma Anemarrhenae 85g, Semen Armeniacae Amarum 85g, Gypsum Fibrosum 130g, Fructus Forsythiae 65g, Radix Glycyrrhizae 65g, Radix Scutellariae 105g, Radix Platycodonis 65g and Radix Bupleuri 65g.
5. a kind of preparation method for the treatment of the Chinese herbal medicine composition of medicine of livestock and poultry respiratory disease as claimed in claim 2, is characterized in that: add the Chinese herbal medicine compound formulation that a certain amount of sucrose, Mel, sodium cyclamate and flavoring orange essence composition make treatment livestock and poultry respiratory disease in described concentrated solution step 10 obtained.
CN201510479049.4A 2015-08-07 2015-08-07 Chinese herbal medicine combination drug treating livestock respiratory diseases and preparation method thereof Pending CN104998034A (en)

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Application publication date: 20151028