CN102188671B

CN102188671B - Chinese medicinal preparation for treating chronic cholecystitis

Info

Publication number: CN102188671B
Application number: CN 201110146238
Authority: CN
Inventors: 隋在云; 徐霞; 贾斌; 梁化举
Original assignee: Shandong Academy of Chinese Medicine
Current assignee: Shandong Academy of Chinese Medicine
Priority date: 2011-06-01
Filing date: 2011-06-01
Publication date: 2012-05-30
Anticipated expiration: 2031-06-01
Also published as: CN102188671A

Abstract

The invention discloses a Chinese medicinal preparation for treating chronic cholecystitis, which is prepared from the following Chinese herbal medicines in part by weight: 25 to 45 parts of giant knotweed rhizome, 20 to 50 parts of virgate wormwood herb, 25 to 45 parts of bupleurum, 30 to 50 parts of longhairy antenoron herb, 20 to 40 parts of gardenia, 20 to 40 parts of ash bark, 15 to 35 parts of Chinese pulsatilla root, 10 to 30 parts of curcuma aromatica, 10 to 30 parts of yanhusuo, 10 to 30 parts of hawthorn fruit and 5 to 15 parts of common vladimiria root. Experiments prove that the Chinese medicinal preparation (Jinhudankang granules) has the obvious effects of bacteriostasis (in vivo and in vitro) inflammation resistance, analgesia and gallbladder normalizing, and is obviously superior to inflammation diminishing and gallbladder normalizing capsules serving as positive medicines in aspects of bacteriostasis, analgesia and gallbladder normalizing.

Description

A kind of Chinese medicine preparation of treating chronic hepatobiliary inflammation

Technical field

The present invention relates to a kind of Chinese medicine preparation of treating chronic hepatobiliary inflammation.

Background technology

Chronic cholecystitis chronic cholecystitis is the chronic pathological changes of gallbladder, and great majority merge cholelithiasis, and minority is non-cholelithiasis property chronic cholecystitis.Be clinical commonly encountered diseases, frequently-occurring disease.Epidemiological study shows that the sickness rate of cholelithiasis sharply raises in recent years, and the primary disease sickness rate roughly was directly proportional with the age.U.S.'s chronic cholecystitis (cholelithiasis) patient accounts for 10% of country's total population, and Germany accounts for 10%-15%, and China has also reached 10%, middle-aged women even up to 15% [1].Because the primary disease sickness rate is high, complication is many, has a strong impact on people's quality of life.Therefore, the control of chronic cholecystitis (cholelithiasis) more and more receives the common concern of medical circle.Hepatology generally becomes the pillar section office of many hospitals.The method of treatment cholelithiasis has at present: Drug therapy; Ultrasonic rubble; Operation.Rubble all has strict indication with operation, and the misery of bringing to the patient is big, and sequela is serious.Chronic cholecystitis is a prefered method except surgical removal gallbladder medicine, adopts the method for taking medicine, and needs the life-time service antiinflammatory, antimicrobial drug; Liver and kidney is caused certain injury, and in recent years, the unique advantage of Chinese medicine performance aspect treatment of chronic diseases started with from improving the body internal environment; Harmonizing the functional activities of vital QI is removed cholepathia spastica, promotes bile secretion; Improve bile components, increase bile flow, inhibiting bacteria and diminishing inflammation; Multi-level, comprehensive treatments such as human body immunity improving power really are whole conditioning, treating both the principal and secondary aspects of a disease.But find that from the clinical observation of this type medicine the Chinese patent medicine that has gone on the market at present is though quantity is many; But the curative effect that has is not good enough, and the dosage form that has falls behind, and the patient is difficult for accepting; What also have is on the high side, and because primary disease does not receive the constraint of age bracket, in old, young all kinds of crowds, morbidity is arranged all; Therefore and sickness rate is higher, and should the disease number of the infected many, the pharmaceutical requirements amount be big; The scorching Chinese patent medicine of the treatment capsule that has gone on the market at present can't satisfy market demand, so this type drug development has wide market prospect, this research is guidance with the Chinese medical theory; According to the clinical experience of long-term treatment cholecystitis,, carried out selected topic research to the main syndrome of damp-heat cholecystitis.

Summary of the invention

To above-mentioned prior art, the invention provides the Chinese medicine preparation of the good chronic hepatobiliary inflammation of treatment of a kind of therapeutic effect.

The present invention realizes through following technical scheme:

A kind of Chinese medicine preparation of treating chronic hepatobiliary inflammation is processed by following bulk drugs: 25～45 parts of Rhizoma Polygoni Cuspidati, 20～50 parts of Herba Artemisiae Scopariaes, 25～45 parts of Radix Bupleuri; 30～50 parts of Herba Lysimachiaes, 20～40 parts of Fructus Gardeniaes, 20～40 parts of Cortex Fraxinis; 15～35 parts of the Radix Pulsatillaes, 10～30 parts of Radix Curcumaes, Rhizoma Corydalis _(system)10～30 parts, Fructus Crataegi _(stir-fry)10～30 parts, 5～15 parts of Radix Vladimiriaes.

Preferably, process: Rhizoma Polygoni Cuspidati 35g, Herba Artemisiae Scopariae 40g, Radix Bupleuri 35g, Herba Lysimachiae 40g, Fructus Gardeniae 30g, Cortex Fraxini 30g, Radix Pulsatillae 25g, Radix Curcumae 20g, Rhizoma Corydalis 20g, Fructus Crataegi 20g, Radix Vladimiriae 10g (recipe quantity) by following crude drug.

Method for preparing is following:

(1) pre-treatment of medicine:

(1) Rhizoma Corydalis and Fructus Crataegi (stir-fry) are by " concocting method is carried out vinegar system and parching to brown under Chinese pharmacopoeia pharmacopeia this kind item in 2010, or directly purchases processed product.

(2) other 9 herbal medicine is the pharmacopeia decoction pieces in the prescription, and Herba Lysimachiae is cut into segment, and Rhizoma Polygoni Cuspidati is ground into fritter, and the Fructus Gardeniae breaking cellular wall suitably is ground into fritter, and other medicines can supply the use that feeds intake after removing impurity.

(2) extraction and preparation technique of preparation, step is following:

(1) take by weighing above 11 flavor stock of drugs decoction pieces in the prescription ratio, the Rhizoma Corydalis micronizing is a micropowder.

(2) Rhizoma Polygoni Cuspidati, Cortex Fraxini, Fructus Crataegi are put in the same extraction pot, add 75% ethanol of 8 times of weight of medical material, reflux, extract, 2 hours; Filter, medicinal residues add 75% ethanol of 6 times of weight again, the same reflux, extract, 2 times, each 1.5 hours; Filter, merge three times alcohol extract, decompression recycling ethanol also is concentrated into the runny plaste of relative density 1.15～1.20 (60 ℃ of surveys), and thin up to relative density is 1.05～1.10 medicinal liquid; Heated and boiled 10 minutes filters while hot, and deposition is with an amount of hot wash 2 times; Merge washing liquid in filtrating, it is 1.30～1.35 thick paste that water liquid is evaporated to relative density, subsequent use;

(3) Herba Artemisiae Scopariae, Radix Bupleuri, Radix Curcumae, Radix Vladimiriae 4 herbal medicines are put in the volatile oil extraction pot, add the water of 10 times of weight of medical material, with steam distillation distillating extracting oil 4 hours, collect volatile oil, and use the powder-beta-dextrin inclusion, and are subsequent use; Leach the water liquid that extracts behind the volatile oil in addition device collect, medicinal residues and Herba Lysimachiae, Fructus Gardeniae, the Radix Pulsatillae merge, decocte with water 2 times, 2 hours first time; 1.5 hours for the second time, filter, merge the water liquid behind 2 decocting liquid and the said extracted volatile oil, be evaporated to relative density and be 1.10～1.12 medicinal liquid; Under fully stirring, slowly add 95% ethanol of 1.5 times of weight of medicinal liquid, stir, left standstill 48 hours; Filter, decompression recycling ethanol and to be concentrated into relative density be 1.30～1.35 thick paste, subsequent use;

(4) thick paste that thick paste that step (2) is prepared and step (3) prepare merges, and it is an amount of to add Rhizoma Corydalis micropowder and dextrin, mixing, and vacuum drying is pulverized, and adds β-CD inclusion complex and an amount of flavoring agent, and mixing is granulated, drying, packing promptly gets.

The method for distilling of the effective extractum of said each medicine is specific as follows:

1, Rhizoma Corydalis micronizing: take by weighing Rhizoma Corydalis in the prescription ratio,, use super micron mill to pulverize and be micropowder in 50～55 ℃ of oven dry, subsequent use.

2, the extraction of the effective extractum of alcohol extraction medicine: take by weighing Rhizoma Polygoni Cuspidati, Cortex Fraxini, Fructus Crataegi 3 herbal medicines in the prescription ratio, add 75% ethanol of 8 times of amounts of quality of medicinal material, reflux, extract, 2 hours filters; Medicinal residues add 6 times of 75% ethanol, and the same reflux, extract, 2 times each 1.5 hours, filters; Merge three times alcohol extract, decompression recycling ethanol also is concentrated into relative density 1.15～1.20, the runny plaste of (60 ℃ of surveys), the medicinal liquid of thin up to 1.05～1.10; Heated and boiled 10 minutes filters while hot, and deposition is with an amount of hot wash 2 times; Merge washing liquid in filtrating, water liquid is evaporated to the thick paste that relative density is 1.30～1.35 (60 ℃ of surveys), and is subsequent use.

3, contain the extraction of volatile oil in the volatile oil medicine: take by weighing the water that Herba Artemisiae Scopariae, Radix Bupleuri, Radix Curcumae, Radix Vladimiriae 4 herbal medicines add 10 times of amounts,, collect volatile oil with steam distillation distillating extracting oil 4 hours, subsequent use; Leach the water liquid that extracts behind the volatile oil, device is collected in addition, and medicinal residues are incorporated in the following water decoction-alcohol sedimentation medicine, carry out decocting again and extract.

4, the extraction of water decoction-alcohol sedimentation medicine: take by weighing Herba Lysimachiae, Fructus Gardeniae, the Radix Pulsatillae 3 herbal medicines in the prescription ratio,, add the water of 10 times of amounts, decocted 2 hours with 4 flavor medicinal residues merging behind the extraction volatile oil; Filter, medicinal residues add 8 times water again, decoct 1.5 hours, filter; Merge the water liquid behind 2 decocting liquid and the said extracted volatile oil, be evaporated to relative density and be 1.10～1.12 medicinal liquid, under fully stirring, slowly add 1.5 times of 95% ethanol and make deposition (it is 57% that medicinal liquid contains alcohol); Stir, left standstill 48 hours, filter; Decompression recycling ethanol, and be concentrated into the thick paste that relative density is 1.30～1.35 (60 ℃ of surveys), subsequent use.

The preparation of said volatile oil inclusion complex is specific as follows:

Get the volatile oil of extraction, with isopyknic dehydrated alcohol dilution, subsequent use; Take by weighing the β-CD that is equivalent to 8 times of weight of volatile oil again, add entry in the ratio of β-CD: water=1g: 25ml, slight fever makes dissolving, and to keep solution temperature be 35 ℃; Under agitation, slowly splash into the ethanol liquid of volatile oil, add continued and stirred 3 hours; Put 0～4 ℃, leave standstill 12h, sucking filtration; Filter cake is put 40～45 ℃ of dryings, and porphyrize is subsequent use.

The preparation of said shaped granule is specific as follows:

Water decoction-alcohol sedimentation cream and alcohol extraction cream are merged, add Rhizoma Corydalis micropowder and an amount of dextrin, mixing, vacuum drying is pulverized, and adds β-CD inclusion complex and an amount of flavoring agent, and mixing is granulated, drying, packing promptly gets.

The function of Chinese medicine preparation of the present invention with cure mainly for: we have removing damp-heat, depressed liver-energy dispersing and function of gallbladder promoting, the effect of regulating QI to relieve pain; Cure mainly the damp-heat type chronic cholecystitis.Disease is seen upper right abdomen persistence distending pain, and pain is drawn the shoulder back of the body, companion's sense of heaviness or heating, and bitter taste in the mouth and dry throat, nausea and vomiting, constipation, upper right abdominal pressure pain, muscle tonus, tenderness can touch gallbladder, red tongue, yellowish fur, wiry and frequent pulse or the stringy and rolling pulse of enlargement sometimes.

In the prescription of the present invention, contained effective ingredient of medicine and main component physicochemical property are summarized as follows:

1. Rhizoma Polygoni Cuspidati: Rhizoma Polygoni Cuspidati is this preparation monarch drug, is dry rhizome and the root of polygonaceae plant Rhizoma Polygoni Cuspidati Polygonum cuspidatum Sieb.et Zucc..Root contains dissociated anthraquinone and anthraquinone glycoside.These compositions have emodin (emodin); Emodin-6-methyl ether (physcion), chrysophanol (chrysophanol), chrysophanic acid (rhein); Anthracene glycoside A (anthragly-coside A; Be emodin-6-methyl ether-8-O-D-glycoside), anthracene glycoside B (anthraglycoside B, i.e. emodin-8-O-D-glycoside).

Contain resveratrol (resveratrol) in the root, Polydatin (polydatin, piceid, promptly 3,4 ', 5-resveratrol-8-β-D-glycoside) two kinds of stilbene compounds.

Rhizoma Polygoni Cuspidati contains a certain amount of tannin.From root, isolate following nine kinds of phenolic constituents: fallacinol (fallacinol); 6-hydroxyl aloe-emodin (citreorosein), emodin-8-monomethyl ether (questin), 6-hydroxyl aloe-emodin-8-monomethyl ether (questinol); Protocatechuic acid (protocatechuic acid); Catechin [(+)-catechin], 2,5-dimethyl-7-hydroxyl chromone (2; 5-dimethyl-7-hydroxychromone); 7-hydroxyl-4-methoxyl group-5-methylcoumarin smart (7-hydroxy-4-methoxy-5-methylcoumarin) and Semen Cassiae pine-8-O-D-glycoside (torachrysone-8-O-D-glucoside) is isolated a kind of new naphthoquinone, 2-methoxyl group-6-acetyl group-7-methyl juglone (2-methoxy-6-acetyl-7-methyl juglone) simultaneously.

Also contain three anthraquinone in the Rhizoma Polygoni Cuspidati; 19 flavone compounds; Isolation identification Quercetin (quercetin); The Arabic glucoside (quercetin-3-arabinoside) of Quercetin-3-, Quercetin-3-rhamnoside (quercetin-3-rhamnoside), Quercetin-3-rhamnoside (quercetin-3-glucoside); Quercetin-3-galactoside (quercetin-3-galactoside), three derivants of luteolin-7-glycoside (luteolin-7-glucoside) and Herba Apii graveolentis flavin (apigenin).From Rhizoma Polygoni Cuspidati, also isolate glucose frangulin (glu-cofraangulin).From Rhizoma Polygoni Cuspidati, also isolate two 1,4-benzoquinone long-chain terpenoids, one of them called after plastoquinone.From root, isolate a kind of polysaccharide, molecular weight is about 6000, contains 38 monosaccharide, is D-glucose, D-galactose, D-mannose, L-rhamnose, L-arabinose, and proportion of composing is 28: 4: 4: 1: 1.The free amino acid that contains 12.99mg/g in the Rhizoma Polygoni Cuspidati also contains multiple inorganic constituentss such as Cu, Fe, Mn, Zn and K.

Modern study shows that the anthraquinones in the Rhizoma Polygoni Cuspidati is hepatic cholagogic and antibiotic, antiviral active substance, can obviously increase the hepatic bile secretion and the Oddi's sphincter that relaxes, and has report 20% Rhizoma Polygoni Cuspidati fluid that hepatitis B antigen (HBSAg) is had the obvious suppression effect.The Rhizoma Polygoni Cuspidati Study on extraction is shown its contained anthraquinones is in decocting extracts, owing to receive the effect of water, heat; The combined anthraquinone facile hydrolysis generates dissociated anthraquinone; And dissociated anthraquinone also is prone to decompose in decoction process, and redox reaction takes place, thereby causes total anthraquinones content to descend.Mainly contain anthraquinone glycoside composition and this constituents unstable character in decocting according to Rhizoma Polygoni Cuspidati, thus in this preparation process, adopt ethanol to extract to Rhizoma Polygoni Cuspidati, with the abundant extraction of guaranteeing effective ingredient and the stability of extracting composition.

2, Herba Artemisiae Scopariae: Herba Artemisiae Scopariae is the dry aerial parts of feverfew BINHAO Artemisia Scoparia Waldst et kit or Herba Artemisiae Scopariae Artemisia Capilaris Thunb., and its contained main component is Coumarins, wrap former ketone, flavonoid, chlorogenic acid, coumaric acid, organic acid, the multiple composition of volatilization wet goods.Chlorogenic acid (Chlorogenic acid) is one of main water soluble ingredient of Herba Artemisiae Scopariae.The Coumarins composition comprises 6, ayapanin, scopoletin, 6-hydroxyl-ayapanin, capillarin.The chromone constituents mainly comprise capillarisin, 7-methyl capillarisin, 4 '-the methyl capillarisin.Flavones ingredient mainly comprise arcapillin, different arcapillin, cirsimaritin, 3 '-methoxyl group cirsimaritin, genkwanin, isorhamnetin, Quercetin, rhamnocitrin, 4 '-eupatolitin, hyperin, Radix et Caulis Opuntiae Dillenii glycoside, rutin etc.Coumaric acid and other organic acid compositions mainly comprise capillartemisin A, B, and deoxidation capillartemisin, BINHAO contain chlorogenic acid (Chlorogenic acid), salicylic acid, Azelaic Acid, burnt gallotannin, oxalic acid.The volatile oil composition comprises that mainly monoterpenes compositions such as acetylene compound such as Herba Artemisiae Scopariae diine, O-methoxy Herba Artemisiae Scopariae diine, capillin, Herba Artemisiae Scopariae alkynol comprise australene; Nopinene; P-ymene etc.; The sesquiterpenoids composition comprises beta-elemene, β-caryophyllene, α-humulene etc., and other volatile oil composition comprises eugenol, methyleugenol etc.Aldehyde, ketonic compound composition comprise parahydroxyacet-ophenone, methyl heptenone, 4-hydroxyl-3-methoxylbenxaldehyde, hutanal, alditol.Other chemical compound mainly comprises cupreol, plant estrogen, choline etc.

Modern pharmacological research shows; Herba Artemisiae Scopariae water decoction, hot water extract, infusion, volatile oil, alcohol extract etc. all have obvious promotion bile secretion and Excretion; Also have simultaneously protect the liver, multiple efficacies such as antiinflammatory, analgesia, this shows that contained water soluble ingredient of Herba Artemisiae Scopariae and volatile oil are the main effective ingredient of clearing heat secreting bile.Mainly contain water solublity active ingredient chlorogenic acid and a small amount of volatilization oil properties according to Herba Artemisiae Scopariae, in preparation technology, extract volatile oil earlier, water boiling and extraction water soluble ingredient again, and remove the water-insoluble impurity of part with ethanol precipitation.

3. Radix Bupleuri: Radix Bupleuri mainly contains saikoside and corresponding with it sapogenin.The Bupleurum falcatum root contains that total saikoside is about 2.8%, and isolating saponin has a, b, c, d4 kind, and sapogenin has 7 kinds, i.e. Saikogenin A, B, C, D, E, F, G.According to inferring that A, B, C, D are not true property sapogenin, but in course of reaction the secondary product by Saikogenin E, F, G and reagent reacting respectively.Saikoside a, d are one of main effective ingredient of Radix Bupleuri.In addition, Radix Bupleuri also contains rutin, volatile oil (for bupleurumol bupleurmol), fatty oil (for glyceride such as oleic acid, linoleic acid, Palmic acid, stearic acid), hitodesterol, adonistal, triterpenoid saponin glucose etc.The Radix Bupeuri Scorzonerfolii. herb contains compositions such as isorhamnetin, Quercetin, isoquercitin, globulariacitrin and narcissin; The contained flavonoid substance of the stem and leaf of Radix Bupleuri and Radix Bupeuri Scorzonerfolii. is kaempferitrin and kaempferol-7-frangulin, and B. kunmingense Y. Li et S. L. Pan contains the twice that the saponin amount is a Radix Bupleuri.The Radix Bupleuri kind of being used as medicine is more; Difference to some extent between each kind of its composition; It is main component that summary gets up to have the saikoside class; Volatile oil polyacetylene constituents, coumarin, lignans, flavones ingredient, plant sterol constituents and other organic acid composition are arranged in addition, and the used Radix Bupleuri of this new drug is through being accredited as Radix Bupleuri.

Modern pharmacological research shows that saikoside and volatile oil all are the main effective ingredient of Radix Bupleuri; The central nervous system had multiple physiologically actives such as tangible analgesia, analgesic, cooling, antitussive; Radix Bupleuri saponin and volatile oil have a tangible antiinflammatory action to rat foot is swollen, according to the contained main effective ingredient of the Radix Bupleuri characteristics that are water-solubility saponin and volatile oil, so in preparation technology first distillating extracting oil; Water boiling and extraction water soluble ingredient again; And remove partial impurities with ethanol precipitation, to reach fully effective component extracting, can reduce the purpose of consumption again.

4, Herba Lysimachiae: the Herba Lysimachiae master contains flavonoid, glycoside, tannin, volatile oil, aminoacid, choline, sterin, potassium chloride etc.In recent years, therefrom isolation identification went out 6 chemical compounds, was respectively Quercetin, Quercetin-3-O-glucoside (quercetin-3-O-glucoside), kaempferol (kaempferol), kaempferol-3-O-galactoside (kaempferol-3-O-galactoside), Rhizoma Kaempferiae-3-O-Margarita three glucosides (kaempferol-3-O-lysima-chiatroside) and 3; 2 ', 4 ', 6 '-tetrahydroxy-4; 3 '-dimethoxy chalcone derivative (3; 2 ', 4 ', 6 '-tetrahydroxy-4; 3 '-dimethoxy-chalcone), also therefrom isolate multiple inorganic constituentss such as NaCl and KCl simultaneously.Main component is a 1-thatch ketone (1-pinocamphone) in the HERBA GLECHOMAE volatile oil, 1-menthone, australene, nopinene, limonene, 1, and (1,8-cineol), paracymene etc. still contain stachyose etc. to the 8-eucalyptol in addition.

Modern pharmacological research shows that Herba Lysimachiae decocting liquid has curative effect preferably for rat oral gavage people medicine treatment cholelithiasis and non-bacterial biliary tract infection.The characteristics and the decocting liquid that mainly contain water soluble ingredient according to Herba Lysimachiae are effective to the animal function of gallbladder promoting, thus in extraction process, adopt the effective extractum of water boiling and extraction, and remove partial impurities with the alcohol deposition.

5. Fructus Gardeniae: Fructus Gardeniae mainly contains iridoid glycosides, organic acid, pigment and other composition.Iridoid glycosides mainly comprises geniposide (geniposide; Geniposide); Gardenoside, genipin gentiobiose glycosides, shanzhiside, Fructus Gardeniae ketoside, Herba Paederiae time glycoside methyl ester, take off acetyl asperuloside acid methyl ester, Geniposidic acid; 10-O-acetyl genipin glucoside, 6 " O-is to coumaric acyl genipin-gentiobioside, genipin-1-β-Fructus Vitis viniferae glycoside, and jasminoidin is one of main effective ingredient of Fructus Gardeniae.The organic acid composition is isolated the benzenpropanoic acid biological ester that forms with quininic acid of acid that spreads out from the acetone-water extract; They are chlorogenic acids, 3; 4-two-O-caffeoylquinic acids, 3-O-caffeoyl-4-O-Semen Sinapis acyl quininic acid, 3; 5-two-O-caffeoyl-4-O-(3-hydroxy-3-methyl) glutaryl quininic acid, 3,4-caffeoyl-5-(3-hydroxy-3-methyl glutaryl) quininic acid, jasminoidin (jasminoidin) Picrocrocinic acid.The pigment composition comprises and contains flavonoid gardenin, triterpenoid compound crocin and crocetin and homologue thereof; Be the rare water-soluble carotenoid class of nature; Also contain α-Stigma Croci glycoside unit, gardenia blue pigment and be make capejasmine cycloolefines ether terpene glycoside (like geniposide) under glucose enzyme or lactobacillus with the lower blue material of primary amine (capital propylhomoserin, isoleucine, glutathion, casein etc.) reaction generation water solublity, absorption maximum is at 600～625nm.Other composition comprises D-mannitol, cupreol, nonacosane.

Fructus Gardeniae decocting thing and alcohol extract all have tangible choleretic effect; Character according to main moisture soluble gardenia glycoside effective ingredient in the Fructus Gardeniae; This composition all has dissolubility preferably in water, alcohol, extract effective extractum and remove partial impurities so in extraction process, adopt water decoction-alcohol sedimentation to form sediment.

6, Cortex Fraxini: the Cortex Fraxini master contains the Coumarins chemical compound, and aseculin (horse chestnut bark glycoside, esculin, aesculin), aesculetin (esculetin, esculetin, aesculetin), fraxin (Chinese ash), fraxetin (fraxetin, fraxetin) etc. are arranged.The fraxinus rhynchophylla Hance master contains aseculin and aesculetin, reports that above-mentioned binary content is 3.3%～3.4%, and report contains aseculin 3.32%～4.63%, aesculetin 0.25%～0.37% in addition.Chinese ash contains aseculin 0.85%～3.54%, aesculetin 0.03%～0.46%.Other contains fraxetin.The place is lived Chinese ash and is contained Cortex Fraxini first, second element totally 3.2%, and above bibliographical information shows that aseculin and aesculetin are the main effective ingredient of Cortex Fraxini.

Modern pharmacological research shows that Cortex Fraxini first, second element has tangible antiinflammatory action.Peroxidating has inhibitory action to aesculetin to rat liver microsomes.According to mainly containing fat-soluble aseculin in the Cortex Fraxini; The character of Coumarins chemical compounds such as aesculetin and water solublity glycoside; In extraction process, adopt the alcohol heating reflux extraction that the element of the second species is all had fine dissolubility, to guarantee the abundant extraction of two effective constituents.

7, the Radix Pulsatillae: mainly contain two constituents in these article, i.e. erysidum (ranunculin) and catabolite thereof and triterpene saponin constituents.Saponin (C ₄₅H ₇₆0 ₂₀) content is about 9%, hydrolysis produces triterpene sapogenin (C ₃₀H ₄₈O ₄), glucose, rhamnose and a unknown sugar.And contain Anemonin and (have another name called anemonin, anemonin).The herb that digs up the roots contains Radix Pulsatillae spirit (okinalin), and the Radix Pulsatillae is because of (okinalein).

Up-to-date discovers, the Radix Pulsatillae contains the acid Saponin of a plurality of new triterpeness, and glycoside unit is a betula camphor mostly.At first be to isolate 23-hydroxyl radical white birck acid (anemosapogenin).Subsequently isolation identification anemoside A ₃(anemoside A ₃), i.e. anemoside A (pulchinenoside A), structure is 3 (S), 2,3-dihydroxy lupin-(3-O-[α-L-rhamnopyranosyl (1 → 2)-α-L arabopyranose base] the strand glycoside of 20 (29)-alkene-28 acid, anemoside B ₄(anemoside B ₄), i.e. anemoside C (pulchinenoside C), structure is 3 (S); 2,3-O-[α-L-rhamnopyranosyl (1 → 2)-α-L arabopyranose base]-28-O-[α-L-rhamnopyranosyl (1 → 4)-β-D-glucopyranosyl (1 → 6)]-β-D-glucopyranosyl ester glycoside of 3-dihydroxy lupin-20 (29)-alkene-28 acid, 3 β; 2,3-dihydroxy-lupin-20 (29)-alkene-28-O-β-D-glucopyranosyl (1 → 6)-β-D-glucopyranosyl ester glycoside (3 β, 2; 3-dihydroxylup-20 (29)-en-28-O-β-D-glucopyranosyl (1 → 6)-β-D-glucopyranoside), 3 β, 2; 3-dihydroxy-lupin-20 (29)-alkene-28-O-α-L-rhamnopyranosyl (1 → 4)-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranside, Pulsatillic acid, structure is 3-ketone group-23-hydroxyl-lupin-20 (29)-alkene-28-acid; 3-O-α-L-arabopyranose base-3 β; 2,3-dihydroxy-lupin-20 (29)-alkene-28-acid (3-O-α-L-arabinopyranosyl-3 β, 2; 3-dihydroxy-lup-20 (29)-en-28-oicacid); Daucosterol (daucosterol), anemoside B (pulchinenoside B), structure is 3-O-α-L-arabopyranose-3 β; 2,3-dihydroxy-lupin-20 (29)-alkene-28-O-α-L-rhamnopyranosyl (1 → 4)-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyanoside.

Modern study shows; Radix Pulsatillae acid juice, water decoction and ethanol extraction all have tangible inside and outside antibacterial action; Its effective ingredient is protoanemonin and Anemonin, and the two all has intensive antibacterial action, and the MLC of protoanemonin is 1.2 * 10 to escherichia coli ^-5～3 * 10 ^-5, be 1.67 * 10 to staphylococcus aureus ^-5, will Jia Shi dysentery bacterium is 1.67 * 10 ^-6, tubercule bacillus is 2.5 * 10 ^-6, some other antibacterial is 1.67 * 10 ^-5～2.5 * 10 ^-5Between.Anemonin is to the MLC of diphtheria corynebacterium, staphylococcus, streptococcus, escherichia coli, tulase etc., 8 * 10 ^-5～2 * 10 ^-6Between.

8, Radix Curcumae: the Radix Curcumae tuber contains volatile oil 6.1%.Wherein main component is a sesquiterpenoids; With zingiberene (zingiberene) serves as at most, secondly is α-and β-Radix Curcumae alkene (curcumene).β-Radix Curcumae alkene and zingiberene are metamers, metameric colors, and α-Radix Curcumae alkene is aromatization then.Sesquiterpene accounts for 65.5% (being mainly curcumene) of volatile oil, and sesquiterpene alcohols accounts for 22%; Also contain camphene (camphene) 0.8%, Camphora 2.5%, curcumin (curcumine) 0.3%, and demethoxycurcumin, bisdemethoxycurcumin, turmerone, aryl turmerone, Eucarvone and phellandrene etc.Also contain curcumenol and curdione.Winter the person of gathering to contain volatile oil more.

Near from the high molecular component of hot water extraction, separate three kinds of polysaccharide.Polysaccharide A is by the L-rhamnose: L-arabinose: D-xylose: D-galactose: D-glucose: D-galactose A constitutes, and mol ratio is 5: 6: 2: 3: 2: 8; Polysaccharide B is by L-arabinose: D-xylose: D-galactose: D-glucose: D-galactose A constitutes, and mol ratio is 1: 6: 2: 6: 1: 2; Polysaccharide C is by rhamnose: arabinose: D xylose: D-galactose: D-glucose: D-galactose A constitutes, and mol ratio is 2: 8: 3: 6: 14: 3.α-4,6 branch glucosan is a high activity partially partly, accounts for large percentage.Radix Curcumae has regulating qi to disperse stagnation, heart fire-clearing upset-relieving, the effect of promoting the function of the gallbladder to alleviate jaundice; Modern pharmacological research shows that volatile oil has function of gallbladder promoting and hepatoprotective effect, can promote biliary generation and secretion, and the contraction gallbladder is arranged, and promotes the effect that bile is discharged, and makes urobilinogen minimizing in the urine.The ethanol extraction of Radix Curcumae is to CCl ₄Due to hepatic injury significant inhibitory effect is arranged, volatile oil CCl ₄With the toxic hepatitis due to the D-galactosamine reduction SGPT is arranged; Improve the blood plasma total protein, promote that albumin is synthetic and suppress the effect that gamma globulin generates, and can make mitochondrion of impaired hepatocyte and rough endoplasmic reticulum recover normal; This shows that volatile oil is the active component that the function of gallbladder promoting of Radix Curcumae protects the liver; Mainly contain the volatilization oil properties according to Radix Curcumae, so in this preparation technology, extract volatile oil earlier, the water liquid behind medicinal residues and the extraction volatile oil carries out water decoction-alcohol sedimentation again.

9, Rhizoma Corydalis: mainly contain alkaloid, it is about 0.65% wherein to belong to tertiary amines person's content, belongs to quaternary amines person about 0.3%.Separated having of obtaining: d-corydaline (the Rhizoma Corydalis first is plain); Dl-first hydrogen palmatine (tetrahydropalmatine); Protopine (Rhizoma Corydalis third element); L-Tetrahydrocoptisine (the Rhizoma Corydalis fourth is plain); Dl-Tetrahydrocoptisine (Rhizoma Corydalis penta element); L-tetrahydrocolumbamine (oneself is plain for Rhizoma Corydalis); Corybulbine (Rhizoma Corydalis is plain heptan); β-homochelidonie (Rhizoma Corydalis rope in the third of the twelve Earthly Branches); Coptisine; 13-Methylpalmatine (dehydrogenation Rhizoma Corydalis first is plain); Rhizoma Corydalis amine; Nearly 20 kinds of dehydrogenation Rhizoma Corydalis amine and Columbamine etc.Wherein be pain relieving and the stronger composition of sedation in the Rhizoma Corydalis with the tetrahydropalmatine, the active component of the routed soup of dehydrogenation Rhizoma Corydalis first prime system prevention gastroduodenal.In addition, still contain lot of starch and compositions such as a small amount of volatile oil and resin.Also contain inorganic elements Mn, Sr, Fe, Pb, Cu, Zn, Co etc.In addition, oneself is plain, the ninth of the ten Heavenly Stems is plain, the last of the ten Heavenly stems is plain and sub-element still to contain former Rhizoma Corydalis.Element is the d-boldine dimethyl ether through identifying plain and last of the ten Heavenly stems in the ninth of the ten Heavenly Stems; Own element and sub-element are L-first hydrogen Columbamine.Tetrahydropalmatine (Tetrahydropalmatine, C ₂₁H ₂₅NO ₄, Tetrahydro palmatine), be soluble in ether, chloroform, dissolve in the dehydrated alcohol, dissolve in the ethanol part omitted, in diluted acid, be prone to dissolve, insoluble in water or alkali, meet FeCl ₃Become blackish green.Tetrahydropalmatine is heated and is prone to be oxidized to palmatine, and palmatine does not have analgesic activity.The Rhizoma Corydalis total alkaloids analgesic activity is about 40% of morphine, and the strongest with the plain analgesic activity of second in the alkaloid, tetrahydropalmatine can produce drug resistance to the analgesic activity of rat, slowly and with morphine the drug resistance that intersects is arranged than morphine.Rhizoma Corydalis and second element thereof have obvious sedative-hypnotic effect, and rat is also had the slight effect that reduces body temperature.

Bibliographical information; Adopt merceration, percolation, three kinds of methods of hot reflux to extract the tetrahydropalmatine in the article of giving birth to and the vinegar goods, and with its content of thin layer spectrophotometry, experimental result show that extracting yield with alcohol heat reflux is higher than percolation; Percolation is higher than cold-maceration, and the vinegar goods are higher than the article of giving birth to.Rhizoma Corydalis vinegar system, alkaloid in the Rhizoma Corydalis and acetic acid are combined into alkaloidal acetate, and in the soluble in water and ethanol, therefore tradition thinks that strengthening analgesic effect after the Rhizoma Corydalis vinegar system is science.This preparation is used to be the vinegar goods, in water and ethanol, all is prone to stripping, but is prone to be oxidized to the palmatine of no analgesic activity owing to Rhizoma Corydalis second element in decocting boils is heated, so in extraction process, adopt ethanol refluxing process to extract.

10, Fructus Crataegi: mainly contain the triterpenes liposoluble constituent in the Fructus Crataegi; Comprise ursolic acid (ursolic acid); Oleanolic acid (oleanolic acid), Crataegolic acid (crataegolic acdi), acanthoic acid (acantholic acid) and Fructus Crataegi α-ruscogenin (crataegusa-sapongenin).Also contain more than 30 kind of flavonoid glycoside such as flavonoid glycoside, flavonol and glycoside, Quercetin and glycoside thereof, nimbecetin and derivant thereof, wuzishan short, bristly hair or beard glycosides, flavanone glycosides and glycosides compound thereof, still contain a large amount of organic acid compositions, isolating have chlorogenic acid (chlorogenic acid), caffeic acid (caffeic acid), tannin, an acid anhydride of tanning (phlobaphene); Epicatechol (L-epicatechol), choline, acetylcholine, histamine, trimethylamine; Isobutylcarbylamine, isobutyl amine, ethamine and DMA, β-steroid sterin, stearic acid; Citric acid, Palmic acid, adenine, gland glycoside, pectin, sucrose, sorbitol; Saponin, protein, fat, digestive enzyme, pigment; Ferrum, inorganic salts such as manganese, thirty alkane, 29 alcohol, carotene and a large amount of vitamin C.Its contained main effective ingredient ursolic acid (vrsolic acid) is by white, needle-shaped crystals (ethanol) that mp is 277-8 ℃, and [α]+65.3 ° (C=0.45, methanol) is soluble in methanol, ethanol, ether, chloroform, is insoluble in water, and its structural formula is seen VIII.

Modern study shows that Fructus Crataegi has blood pressure lowering coronary dilating and cardiotonic, and Fructus Crataegi is used to the key medicine that helps digestion since ancient times, it is said and is longer than the inner product that disappears especially; Pharmacological testing shows, oral Fructus Crataegi ability gastric acid secretion, the activity of increase enzyme; Fructus Crataegi (parched to brown) after the process of preparing Chinese medicine, the dyspepsia and intestinal stasis relieving effect strengthens, and has both contained liposoluble constituent according to Fructus Crataegi; The character that contains water soluble ingredient again adopts in extraction process the element of the second species is all had a good solubility, and alcohol heating reflux extracts.

11, Radix Vladimiriae: mainly contain lactone compounds such as GUM GUAICE element, Folium eucalypti globueli (Eucalyptus globulus Labill.) lactone, germacrane lactone and wooden lactone in the Radix Vladimiriae, and the volatile oil composition.Existing division is following:

(1) lactone compound

GUM GUAICE compounds: 3 β-acetyl group-11 β H-guaiacyl-4 (15), 10 (14)-diene-12,6 α-lactones (3 β-Acetoxy-11 β H-guaia-4 (15), 10 (14)-diene-12 are arranged; 6 α-olide), 10 α, 14-epoxy-11 β H-guaiacyl-4 (15)-alkene-12,16 α-lactone (10 α, 14-Epoxy-11 β H-guaia-4 (15)-ene-12; 6 α-olide), 3 beta-hydroxies, 10 α, 14-epoxy-4 β, 11 β H-guainane-12,6 ' α-lactone (3 β-hydroxy-10 α; 14-Epoxy-4 β, 11 β H-guaia-12,6 α-olide), 10 β, 14-dihydroxy-11 α H-guaiacyl-4 (15)-alkene-12; 6 α-lactone (10 β, 14-Oihydroxy-11 α H-guai-4 (15)-ene-12,6 α-olide), 3 β, 11 beta-dihydroxy guaiacyls-4 (15); 10 (14-diene-12,6 α-lactone (3 β, 11 β-Dihydroxy guaia-4 (15), 10 (14)-diene-12; 6 α-olide), 10 β, 14-dihydroxy-11 α H-guaiacyl-4 (15)-alkene-12,6 α-lactone (10 β, 14-Dihydroxy-11 α H-guaia-4 (15)-ene-12; 6 α-olide), 3 β-acetyl group guaiacyl-11 (13), 4 (15), 10 (14)-triolefins-12,6 α-lactone (3 β-Acetoxyguaia-11 (13); 4 (15), 10 (14)-triene-12,6 α-olide), 3 beta-hydroxies-11 α H-guaiacyl-4 (15), 11 (14)-diene-12; 6 α-lactone (3 β-Hydroxy-11 α H-guaia-4 (15), 11 (14)-diene-12,6 α-olide).

Folium eucalypti globueli (Eucalyptus globulus Labill.) lactone: mainly contain 1 β, 2 alpha-dihydroxy-s-11 β H-cineole-4 (15)-alkene-12,6 α-lactone (1 β; 2 α-dihydroxy-11 β H-eudesm-4 (15)-ene-12,6 α-olide), 1 β, 4 alpha-dihydroxy-s-11 β H-eudesmane-12; 6 α-lactone (1 β, 4 α-Dihydroxy-11 β H-eudesman-12,6 α-olide), 1 Alpha-hydroxy cineole-4 (15); 11 (13)-diene-12; 6 α-lactone (1 α-Hydroxyeudesm-4 (15), 11 (β)-diene-12,6 α-olide).

Germacrane lactone: plain-1 (10) E of 15-acetyl group-11 β H-Bulgarian geranium is arranged, 4E-diene-12,6 α-lactone (15-Acetoxy-11 β H-germacre-1 (10) E, 4E-diene-12; 6 α-olide), plain-1 (10) E of 11 β H-Bulgarian geraniums, 4E-diene-12,6 α-lactone (11 β H-Germacra-1 (10) E, 4E-diene-12; 6 α-olide), plain-1 (10) E of 15-hydroxyl-11 β H-Bulgarian geranium, 4E-diene-12,6 α-lactone (15-Hydroxy-11 β H-germacra-1 (10) E, 4E-diene-12; 6 α-olide), plain-1 (10) E of 15-acetyl group Bulgarian geranium, 4E, 11 (β)-triolefin-12,6 α-lactones (15-Aceboxygermacra-1 (10) E; 4E, 11 (13)-triene-12,6 α-olide), plain-1 (10) E of Bulgarian geranium; 4E, 11 (13)-triolefins-12,6 α-lactone (Germacre-1 (10) E; 4E, 11 (13)-triene-12,6 α-olide).

Constuslactone class: contain Radix Vladimiriae lactone (Mokko lactone), Dehydrocostunolide lactone (Dehydrocostuslactone), 11; 13 α-dihydro Zha Lusangning C (11,13 α-Dihydrozaluzanin C), dihydrodehydrocostus lactone (Dihydrodehydrocos tuslactone).

(2) volatile oil: it is about 0.3% to contain volatile oil in the Radix Vladimiriae root, and the physicochemical constant of oil is proportion

index of refraction

specific optical rotation

(ethanol).

According to the character of main volatile oil of Radix Vladimiriae and part water soluble ingredient, in preparation technology, extract volatile oil earlier, water liquid and medicinal residues carry out water decoction-alcohol sedimentation again, with the effective ingredient of abundant extraction Radix Vladimiriae.

Set forth the indication pathogenesis and the rule of treatment with theory of Chinese medical science:

Chronic cholecystitis belongs to the category of motherland's medical science " hypochondriac pain ", " jaundice ", and the sick position of primary disease concerns the closest at gallbladder with liver, spleen, stomach.Liver and gallbladder are lived together the side of body down first, belong to the exterior and the interior each other through venation, and liver controlling conveyance and dispersion, property happiness bar reach, and its property liter is sent out; The gallbladder storing refined juice, main resolution, its property is logical falls.Second a dirty internal organs, one rise and one drop, mutual dependence for existence is a usefulness on the physiology, the change of disease that influences each other on the pathology is so hepatopathy must elder generation and gallbladder; Second the taste dependent territory is the ground in Central Region, the pivot of rising and falling of QI, and transverse invasion of hyperactive liver-QI is the criminal's of gram spleen soil often, and spleen soil is stopped up stagnant, and wooden strongly fragrant difficulty is stretched, and takes place and cause primary disease.As Lin Peiqin " Lei Zheng Zhi Cai " cloud: " edema with the liver involved property liter looses, and is not held back strongly fragrantly, and Yu Ze is through the QI rising in reverse order, for, for expanding, be vomiting, sick for the rage side of body, for fullness in the chest is not eaten, lientery is the hernia of bursting, all irritability is horizontal determines also ".But the cause of disease differs, and pattern of syndrome is different.The chronic cholecystitis that we cure mainly is due to the damp-heat accumulation.Because of the spleen being in charge of dampness, liver is hidden fire, all sick how damp and hot being harmonious of liver spleen, or addiction to greasy and sweet foods savoury, and cause temper and stop up and stagnate, give birth in damp and hot, or overabundant liver-fire, it is native to restrain spleen, Yin Re and wetting; Or weakness of the spleen and stomach usually, YIN-fire is high to be taken advantage of, and because of wet heat, all can make damp and hot being harmonious, and glued not understanding checked mechanism of qi, causes gallbladder to lose logical falling, and cholestegnosis is obstructed and fall ill.As " bright doctor's fingers and palms " institute's cloud in Huangfu: " damp and hot Sheng and pain in the hypochondrium ".The damp-heat accumulation liver and gall, disorder of QI movement, side of body network is become estranged, so see upper right abdomen persistence distending pain, pain is drawn the shoulder back of the body, companion's sense of heaviness; Contain in damp and hot, then heating, the gallbladder fire is superior, bitter taste then, dry pharynx, damp and hot in resistance; Stomach-QI being unable to descend normally, nausea and vomiting then, intenseness of heat impairment of body fluid, FU QI being obstructed, then constipation etc.Upper right abdominal pressure pain, muscle tonus, tenderness can touch gallbladder, red tongue, yellowish fur, wiry and frequent pulse or the stringy and rolling pulse of enlargement sometimes.Control suitable removing damp-heat, depressed liver-energy dispersing and function of gallbladder promoting, regulating QI to relieve pain.

By monarch, minister, help, make the analysis prescription compatibility of medicines:

The Rhizoma Polygoni Cuspidati bitter cold is gone into liver, gallbladder meridian in the side, and " Chinese Clinical Chinese Materia Medica " carries: " bright clear since book on Chinese herbal medicine sum up it gradually and have effects such as clearing away heat-damp and promoting diuresis, promoting the function of the gallbladder to alleviate jaundice, blood circulation promoting and blood stasis dispelling, detoxifcation pain relieving, purging heat to relax the bowels ".These article have the clinical efficacy of similar Radix Et Rhizoma Rhei, but do not have the fraud that the Radix Et Rhizoma Rhei bitter cold injures one's stomach." property of medicine opinion " year its ability " ... press all pyretic toxicity ".The Herba Artemisiae Scopariae bitter in the mouth is slightly cold, and returns spleen, stomach, liver, gallbladder meridian, the heat clearing away of cold ability, and bitter in the mouth dampness, " Bencao Jingshu " sayed it: " key medicine of dehumidifying heat radiation knot is also." two medicines share ability removing damp-heat, depressed liver-energy dispersing and function of gallbladder promoting, regulating QI to relieve pain, are monarch drug altogether.Radix Bupleuri is bitter, hot, be slightly cold, and returns liver, gallbladder meridian, can soothing the liver dissipating depression of QI; The Herba Lysimachiae slightly sweet flavor, little hardship, master cool in nature goes into the liver and gall warp.The sweet light profit of oozing, little hardship, heat clearing away cool in nature, so the merit of heat-clearing and dampness-resolving is arranged, " Shaanxi Chinese herbal medicine " sayed it: " curing mainly cholecystitis, jaundice "; The Fructus Gardeniae bitter cold is gone into the heart, liver, lung, stomach, tri-jiao channel, and ability heat clearing away, pathogenic fire purging, relieving restlessness with the Li Genghong of its clearing away heat-damp and promoting diuresis of Herba Artemisiae Scopariae compatibility, and make damp and hot heresy by urinating." explaining abstruseness of the canon of materia medica " said: " Zhong Jing uses Fructus Gardeniae more, and Herba Artemisiae Scopariae is got its diuresis and exempts from also damp and hot ".The Cortex Fraxini bitter cold is gone into liver and gall, and it is hot and suffocating to be used for liver and gall, ability heat clearing and damp drying, apocatharsis gallbladder fire; Radix Pulsatillae bitter cold is returned large intestine channel, ability heat-clearing and toxic substances removing removing heat from blood, and " book on Chinese herbal medicine converges and says " carried its ability: " removing heat from blood, repercussive are separated noxious dampness ".Radix Curcumae is arduous, cold, returns liver, the heart, lung meridian, ability regulating qi to disperse stagnation, heart fire-clearing upset-relieving, promoting the function of the gallbladder to alleviate jaundice, its " promoting QI circulation for relieving depression of essentials of Matea Medica speech; Promoting blood circulation and breaking stagnation.Cool heat in the heart, the stagnation of liver-QI of loosing." above Six-element medicine: Herba Lysimachiae, Fructus Gardeniae, Cortex Fraxini, Radix Pulsatillae ability principal drug assistance clearing away heat-damp and promoting diuresis; Radix Bupleuri, Radix Curcumae principal drug assistance depressed liver-energy dispersing and function of gallbladder promoting are ministerial drug altogether.The traditional Chinese medical science thinks that blood vessels are valued for circulation, existing irritability stasis, and blood stasis appears in the stagnation of QI then regular meeting, so diffusing with the Rhizoma Corydalis suffering, hardship is fallen, temperature is led to promoting flow of QI and blood.Fructus Crataegi (parched to brown) is sour, sweet, tepor, returns liver, spleen, stomach warp, ability promoting digestion and invigorating the stomach, circulation of qi promoting dissipating blood stasis.The Compendium of Material Medica speech: " dissipating fluid-retention is eaten, the meat that disappears is long-pending ... the blood pain with distension stagnates." share the ability promoting tissue regeneration by removing blood stasis with Radix Curcumae, Rhizoma Corydalis; The arduous temperature of Radix Vladimiriae is returned spleen, stomach, large intestine, gallbladder meridian, pain relieving during the ability circulation of qi promoting is transferred, and holding concurrently can strengthening the spleen to promote digestion.Compendium of Material Medica speech: " Radix Aucklandiae is the medicine of three warmers edema caused by disorder of QI, and all gas can go up and down "; The hot temperature of Rhizoma Corydalis, Fructus Crataegi, the Radix Aucklandiae, the regulating qi to disperse stagnation pain relieving, the spleen invigorating promoting digestion and removing stagnated food can alleviate the property of the bitter cold of monarch, ministerial drug, and turn round and look at and protect gastric qi, be adjuvant altogether.Radix Bupleuri draws all medicines and goes into gallbladder meridian, the usefulness of messenger drug of holding concurrently.All medicines share plays removing damp-heat altogether, depressed liver-energy dispersing and function of gallbladder promoting, and the merit of regulating QI to relieve pain makes clearing moist heat, QI movement being in harmonious way, all cards are from removing.

Through evidence, Chinese medicine preparation of the present invention (golden as brave as a tiger recovering particles) has tangible bacteriostasis (body is interior, external), antiinflammatory action, analgesic activity and choleretic effect, and obviously is being superior to the positive drug Xiaoyanlidan capsules aspect antibacterial, analgesia, the function of gallbladder promoting.Irritated the as brave as a tiger recovering particles of stomach gold continuous 180 days every day for rat; Its high dose 21.4g/kg reaches 50 times of clinical consumption; To the general situation of rat, blood, routine urinalysis, the equal non-toxic reaction of hepatic and renal function and main organs; Show that the heavy dose of prolonged application of Chinese medicine preparation of the present invention do not have the overt toxicity reaction, its usual amounts of clinical practice is safe.

The specific embodiment

Below in conjunction with embodiment the present invention is further described.The as brave as a tiger recovering particles of described gold is the trade name of Chinese medicine preparation of the present invention.

The golden as brave as a tiger recovering particles of embodiment 1 preparation

Prescription is: Rhizoma Polygoni Cuspidati 35g, Herba Artemisiae Scopariae 40g, Radix Bupleuri 35g, Herba Lysimachiae 40g, Fructus Gardeniae 30g, Cortex Fraxini 30g, Radix Pulsatillae 25g, Radix Curcumae 20g, Rhizoma Corydalis 20g, Fructus Crataegi 20g, Radix Vladimiriae 10g.

Preparation technology is:

(1) pre-treatment of medicine:

(2) extraction and preparation technique of preparation, step is following:

(2) after Rhizoma Polygoni Cuspidati, Cortex Fraxini, Fructus Crataegi mix, with 75% ethanol extraction 3 times, 2 hours first time; Second and third time respectively is 1.5 hours, filters, and merges 3 times alcohol extract; Decompression recycling ethanol also is concentrated into the runny plaste that does not have alcohol flavor (relative density 1.15～1.20,60 ℃ of surveys), and thin up to relative density is 1.08～1.15 medicinal liquid; Heated and boiled 10 minutes, fully mixing filters while hot; Medicinal residues merge washing liquid in filtrating with hot wash 2 times, and water liquid is evaporated to the thick paste that relative density is 1.30～1.35 (60 ℃ of surveys).

(3) Herba Artemisiae Scopariae, Radix Bupleuri, Radix Curcumae, Radix Vladimiriae mix, and extract volatile oil, and are encapsulated with for use with powder-beta-dextrin, leach the water liquid that extracts behind the volatile oil in addition device collect; Medicinal residues and Herba Lysimachiae, Fructus Gardeniae, the Radix Pulsatillae merge, decocte with water 2 times, 2 hours for the first time; 1.5 hours for the second time, filter, merge the water liquid behind 2 decocting liquid and the said extracted volatile oil; Being evaporated to relative density is the medicinal liquid of 1.10～1.12 (60 ℃ of surveys), under fully stirring, slowly adds 1.5 times of 95% ethanol (it is 57% that medicinal liquid contains the alcohol amount), stirs; Left standstill 48 hours, and filtered, decompression recycling ethanol also is concentrated into the thick paste that relative density is 1.30～1.35 (60 ℃ of surveys).

(4) thick paste that thick paste that step (2) is prepared and step (3) prepare merges, and adds the Rhizoma Corydalis micropowder, and an amount of dextrin, mixing, vacuum drying; Pulverize, add β-CD inclusion complex and an amount of flavoring agent, mixing is granulated; Drying is processed the 100g granule, by every bag of 10g packing, promptly gets.

2, the extraction of the effective extractum of alcohol extraction medicine: take by weighing Rhizoma Polygoni Cuspidati, Cortex Fraxini, Fructus Crataegi 3 herbal medicines in the prescription ratio, add 8 times of weight 75% ethanol of medical material, reflux, extract, 2 hours filters; Medicinal residues add 6 times of amount 75% ethanol again, and the same reflux, extract, 2 times each 1.5 hours, filters; Merge three times alcohol extract, decompression recycling ethanol also is concentrated into relative density 1.15～1.20, the runny plaste of (60 ℃ of surveys), the medicinal liquid of thin up to 1.05～1.10; Heated and boiled 10 minutes filters while hot, and deposition is with an amount of hot wash 2 times; Merge washing liquid in filtrating, water liquid is evaporated to the thick paste that relative density is 1.30～1.35 (60 ℃ of surveys), and is subsequent use.

4, the extraction of water decoction-alcohol sedimentation medicine: take by weighing Herba Lysimachiae, Fructus Gardeniae, the Radix Pulsatillae 3 herbal medicines in the prescription ratio,, add the water of 10 times of amounts, decocted 2 hours with 4 flavor medicinal residues merging behind the extraction volatile oil; Filter, medicinal residues add 8 times water again, decoct 1.5 hours, filter; Merge the water liquid behind 2 decocting liquid and the said extracted volatile oil, be evaporated to relative density and be 1.10～1.12 medicinal liquid, under fully stirring, slowly add 1.5 times of 95% ethanol and make deposition (it is 57% that medicinal liquid contains alcohol); After adding, continue to stir 20 minutes, left standstill 48 hours in 0～4 ℃; Filter, decompression recycling ethanol, and to be concentrated into relative density be that the thick paste of 1.30～1.35 (60 ℃ of surveys) is subsequent use.

The preparation of said volatile oil inclusion complex is specific as follows:

Get the volatile oil of extraction, with isopyknic dehydrated alcohol dilution, subsequent use; Take by weighing the β-CD that is equivalent to 8 times of amounts of volatile oil again, add entry in the ratio of β-CD: water=1g: 25ml, slight fever makes dissolving, and to keep solution temperature be 35 ℃; Under agitation, slowly splash into the ethanol liquid of volatile oil, add continued and stirred 3 hours; Put 0～4 ℃, leave standstill 12h, sucking filtration; Filter cake is put 40～45 ℃ of dryings, and porphyrize is subsequent use.

The preparation of said shaped granule is specific as follows:

Water decoction-alcohol sedimentation cream and alcohol extraction cream are merged, add the Rhizoma Corydalis micropowder, add dextrin 30g, mixing, vacuum drying by each recipe quantity thick paste; Pulverize, add β-CD inclusion complex and stevioside 1.5g, mixing is granulated; Drying is processed the 100g granule, by every bag of 10g packing, promptly gets.

The golden as brave as a tiger recovering particles of embodiment 2 preparations

Prescription is: Rhizoma Polygoni Cuspidati 30g, Herba Artemisiae Scopariae 45g, Radix Bupleuri 30g, Herba Lysimachiae 45g, Fructus Gardeniae 25g, Cortex Fraxini 35g, Radix Pulsatillae 20g, Radix Curcumae 25g, Rhizoma Corydalis 15g, Fructus Crataegi 25g, Radix Vladimiriae 13g.

Method for preparing is with embodiment 1.

The golden as brave as a tiger recovering particles of embodiment 3 preparations

Prescription is: Rhizoma Polygoni Cuspidati 40g, Herba Artemisiae Scopariae 30g, Radix Bupleuri 40g, Herba Lysimachiae 35g, Fructus Gardeniae 35g, Cortex Fraxini 25g, Radix Pulsatillae 30g, Radix Curcumae 15g, Rhizoma Corydalis 25g, Fructus Crataegi 15g, Radix Vladimiriae 8g.

Method for preparing is with embodiment 1.

The golden as brave as a tiger recovering particles of embodiment 4 preparations

Prescription is: Rhizoma Polygoni Cuspidati 25g, Herba Artemisiae Scopariae 50g, Radix Bupleuri 25g, Herba Lysimachiae 50g, Fructus Gardeniae 20g, Cortex Fraxini 40g, Radix Pulsatillae 15g, Radix Curcumae 30g, Rhizoma Corydalis 10g, Fructus Crataegi 30g, Radix Vladimiriae 5g.

Method for preparing is with embodiment 1.

The golden as brave as a tiger recovering particles of embodiment 5 preparations

Prescription is: Rhizoma Polygoni Cuspidati 45g, Herba Artemisiae Scopariae 20g, Radix Bupleuri 45g, Herba Lysimachiae 30g, Fructus Gardeniae 40g, Cortex Fraxini 20g, Radix Pulsatillae 35g, Radix Curcumae 10g, Rhizoma Corydalis 30g, Fructus Crataegi 10g, Radix Vladimiriae 15g.

Method for preparing is with embodiment 1.

Experiment 1: the pharmacodynamic study of golden as brave as a tiger recovering particles

Experiment material

One, medicine

The as brave as a tiger recovering particles of gold: adult's consumption: every day three times, each 1 bag, the 10g/ bag, the 1g granule is equivalent to crude drug 3.05g, 30g/70kg=0.4286g/kg=1.307g crude drug/kg, following zoopery is all calculated by grain amount.Lot number is provided: 20010405 by the Drug Manufacturing Room of this institute.

Xiaoyanlidan capsules: Hengshengtang Pharmaceutical Co., Ltd., Xi'an City, lot number: 20001205.

Two, strain

The Quality Control bacterial strain: staphylococcus aureus (26001), escherichia coli (44102), streptococcus faecalis (32221), Bacillus proteus (49102), pseudomonas aeruginosa (10102) are all available from Nat'l Pharmaceutical & Biological Products Control Institute.

Clinical strains: staphylococcus aureus, escherichia coli, streptococcus faecalis, Bacillus proteus, pseudomonas aeruginosa provide by Shandong Qilu Hospital.

Three, reagent

Nutrient agar: chemical reagent work of shanghai Medicine assay office produces, lot number: 980202;

Beef infusion broth: self-control.

The STB test kit, biological engineering High-tech company in Beijing, lot number: 010101.

Cholerythrin standard liquid test kit: biological engineering High-tech company in Beijing, lot number: 010708.

Four, animal

Kunming mouse is purchased university's Experimental Animal Center in Shandong, the quality certification number, No. 200001002, Shandong kinoplaszm word.

The Wistar rat is purchased university's Experimental Animal Center in Shandong, I level animal, the quality certification number, No. 200001003, Shandong kinoplaszm word.

Five, instrument

Supply of equipment maintenance station, the Academy of Medical Sciences, XZC-2B type autocontrol temperature hot-plate instrument Shandong.

YDHP-KR electric constant-temp incubator Ningbo Medical Appliance Factory.

Sharp Instr Ltd. is closed in the wholly foreign-owned Shanghai of WFZ UV-2100 type spectrophotometer.

Six, experimental technique and result

(1) bacteriostatic experiment

1. external plate-steel pipe method will be cultivated each bacterial strain of 24h, get 1 oese in 2ml meat soup, and 37 ℃ increase bacterium 6h (streptococcus faecalis 18h) and then each bacterium liquid are diluted to 10 ^-3, get diluent 1ml again and put into the 30ml agar tube of getting ready, fully be poured onto plate at once behind the mixing; Cold but back is divided in the plate bottom and each medicinal liquid zone of labelling; Put into sterilization steel pipe (7 * 10mm) splash into the respective steel pipe with medicinal liquid, build FE Tiler, 37 ℃ cultivate 24 after; Measure antibacterial ring size (mm) experiment repetition 6 times, the result sees table 1, table 2.

Table 1: golden as brave as a tiger recovering particles to the bacteriostasis of 5 special quality control bacterial strains (n=6, mm)

Table 2: golden as brave as a tiger recovering particles to the plate bacteriostatic experiment of 5 kinds of clinical strains (n=6, mm)

Can find out that by table 1, table 2 golden as brave as a tiger recovering particles has obvious bacteriostasis to Quality Control bacterial strain preceding 4 kinds (staphylococcus aureus, escherichia coli, streptococcus faecalis, Pseudomonas aeruginosas); Clinical strains preceding 3 kinds (staphylococcus aureus, escherichia coli, streptococcus faecalis) is had tangible bacteriostasis, and to the antibacterial ring of Quality Control bacterium obviously greater than antibacterial ring to clinical bacterium.

2. external test tube doubling dilution (mensuration of minimal inhibitory concentration) is got 6 in sterilization test tube; Number consecutively, every pipe adds broth bouillon 2ml under the aseptic condition, adds medicinal liquid 2ml in first pipe then; Take out 2ml behind the mixing and put into second pipe; And the like, to the last a pipe taking-up 2ml discards, and makes into 1: 21: 4 ... 1: 32 various concentration.In each pipe, add again and be diluted to 10 ^-3Each bacterium liquid 0.1ml; And cook meat soup and the original liquid control tube that does not add bacterium liquid; Place 37 ℃ to cultivate 24h, observe the bacterial growth situation and get again and respectively manage liquid and change and kind observe behind 37 ℃ of agar plates, 24h that to have or not bacterial growth, no bacterial growth person be the minimal inhibitory concentration of this medicine to this bacterium; The result does not add the meat soup and the interior no bacterial growth of original liquid control tube of bacterium liquid, and the drug liquid tube result of variable concentrations sees table 3, table 4.

Table 3: to the minimal inhibitory concentration (n=3) of 5 special quality control bacterial strains

Table 4: to the minimal inhibitory concentration (n=3) of 5 kinds of clinical strains

Find out that by table 3, table 4 golden as brave as a tiger recovering particles is 0.041g/ml to Quality Control strain golden color staphylococcus, colibacillary MIC, the MIC of streptococcus faecalis, Pseudomonas aeruginosa, Bacillus proteus is 0.082g/ml; MIC to clinical strains staphylococcus aureus, escherichia coli, Pseudomonas aeruginosa is 0.082g/ml, and the MIC of streptococcus faecalis is 0.164g/ml, and Bacillus proteus is not had external bacteriostasis.

3. bacteriostatic experiment selects for use cholecystitis common pathogen staphylococcus aureus and escherichia coli commentaries on classics to plant in meat soup in the body of golden as brave as a tiger recovering particles; Cultivate 6h for 37 ℃; As original bacteria liquid; To each concentration, the healthy mice of getting body weight 18-20g carries out (MLD) that minimum lethal dose prerun that two bacterial strains cause 100% animal dead records staphylococcus aureus and is 100 times of dilutions with 5% gastric Mucin dilution bacterium liquid, and colibacillary MLD is 1000 times of dilutions.Get 100 of healthy Kunming mouses, be divided at random: blank group, Xiaoyanlidan capsules group, the high, medium and low dose groups of golden as brave as a tiger recovering particles, fasting 6h before the experiment by body weight; Can't help water, the 1h administration is 1 time before experiment, the bacterium liquid 0.5ml of every mouse peritoneal injection MLD concentration; And in infecting back 6h, 24h, 48h, each gastric infusion of 72h 1 time; Observe and write down the death time and accumulative total death toll of infecting each treated animal of back, the result checks through X2, sees table 5, table 6.

Table 5: golden as brave as a tiger recovering particles is to the endogenous protective effect (n=20) of infection of staphylococcus aureus mice

Compare with matched group: * P＜0.05; * P＜0.01; * * P＜0.001

Compare with the Xiaoyanlidan capsules group: ^△P＜0.05

Table 6: golden as brave as a tiger recovering particles is to the endogenous protective effect (n=20) of coli-infection mice

Compare with matched group: * P＜0.05; * P＜0.01; * * P＜0.001

Compare with the Xiaoyanlidan capsules group: ^△P＜0.05

Can find out that by table 5, table 6 golden as brave as a tiger recovering particles is high, middle dose groups has the significant protection effect to the dead mouse due to the infection of staphylococcus aureus, its high dose group action intensity obviously is superior to Xiaoyanlidan capsules; As brave as a tiger recovering particles three dose groups of gold all have the significant protection effect to the dead mouse due to the coli-infection, and its high dose group action intensity obviously is superior to Xiaoyanlidan capsules.

(2) antiinflammatory action of golden as brave as a tiger recovering particles

1. 50 of healthy kunming mices are got in the xylol influence that causes mice ear, body weight 25-30g, and male and female half and half are divided 5 groups at random; Press table 6 dosage gastric infusion, matched group is given the water of equivalent, and for three days on end, the every Mus of 0.5h left side ear is coated with xylene 0.1ml after the last administration; Put to death animal behind the 4h, cut ears, lay round auricle, scales/electronic balance weighing at same position respectively with the card punch of 9mm along the auricle baseline; The weight difference of two ears is the degree of ear swelling, and the result checks through t, presses ^[1]Method is calculated suppression ratio, sees table 7.

Table 7: golden as brave as a tiger recovering particles is to the effect of mice ear (n=10, X ± s)

Compare with matched group: * P＜0.05

Experimental result shows, can obviously alleviate the mice ear degree with matched group than golden as brave as a tiger recovering particles high dose group, and its action intensity is superior to Xiaoyanlidan capsules trend; Wherein dose groups and low dose group also have certain effect trend that alleviates mice ear.

2. golden as brave as a tiger recovering particles is got 50 of healthy male Wistar rats to the influence of rat paw edema; Be divided into 5 groups at random by body weight; Every group 10: matched group, Xiaoyanlidan capsules group, the high, medium and low dose groups of golden as brave as a tiger recovering particles, each group was by dosage gastric infusion in the table, continuous 4 days; In irritating stomach the 2nd day; The formaldehyde 0.1ml of the sufficient plantar subcutaneous injection 2.5% in every Mus left side, respectively at injecting back 1h, 3h, 6h, 24h, reaching 48h with the left and right sufficient sole of the foot of inelastic tape measuring (fixed position) girth, the difference of the left and right sufficient sole of the foot girth of rat is the rat paw edema degree.The result sees table 8.

Table 8: golden as brave as a tiger recovering particles is to the influence of rat paw edema (n=10, X ± s)

Compare with matched group: * P＜0.05; * P＜0.01; * * P＜0.001

Compare with the Xiaoyanlidan capsules group: ^△P＜0.05

Find out that from table 8 golden as brave as a tiger health three dose groups all have the effect of obvious suppression rat paw edema, and high dose group obviously is superior to Xiaoyanlidan capsules.

3. golden as brave as a tiger recovering particles to rat granuloma bullate influence get 50 of healthy male Wistar rats, about body weight 190g, be divided into 5 groups at random: matched group, Xiaoyanlidan capsules group, the high, medium and low dose groups of golden as brave as a tiger health by body weight; Each is organized under the shallow fiber crops of ether, and the sterile working is with cotton balls (heavy 50mg; Through autoclaving and add 0.1ml/ cotton balls of 10mg/ml penbritin) to implant rat both sides axillary region subcutaneous, each group press table 9 dosage filling stomach relative medicine, continuous 7 days simultaneously; Put to death rat on the 8th day, peel off and take out the cotton balls granulation tissue, in baking oven 80 ℃; Weigh after the 2h drying, deduct the raw cotton ball weight, be the granuloma net weight.The result sees table 9.

Table 9: to the bullate influence of rat granuloma (n=10, x ± S)

Compare with matched group: * P＜0.05; * P＜0.01

Experimental result shows that golden as brave as a tiger recovering particles has the obvious suppression effect to the hypertrophy of rat granuloma tissue.

(3) analgesic experiment

1. female Kunming mouse is got in mice hot plate experiment, body weight 22g, and 55 ℃, twice prediction threshold of pain meansigma methods is divided into 5 groups by the threshold of pain: matched group, Xiaoyanlidan capsules group, the high, medium and low dose groups of golden as brave as a tiger recovering particles at random less than 50 of the animals of 30S.Press table 10 dosage gastric infusion 1 time, 0.5h, 1h, 2h respectively survey the threshold of pain 1 time behind the medicine, and the hot plate temperature control occurs licking the threshold of pain of the time second (s) of metapedes as this Mus in 55 ℃ with mice.The result sees table 10.

Table 10: golden as brave as a tiger recovering particles is to the influence of the mice hot plate threshold of pain (n=10, X ± S)

Compare with matched group: * p＜0.05, * * P＜0.01;

Compare with the cholagogue and eliminating inflammation Capsules group: ^△P＜0.05;

Can find out that from table each is organized after the administration threshold of pain of 1h mice and obviously improves, still have tangible effect to the as brave as a tiger recovering particles of 2h gold, three dose groups all obviously are superior to the positive drug Xiaoyanlidan capsules, point out these article to have analgesic activity and longer duration.

2. the experiment of mice acetic acid twisting is got about 60 body weight 22g of Kunming mouse, and male and female half and half are divided into 6 groups at random by body weight: matched group, Xiaoyanlidan capsules group, the high, medium and low dose groups of golden as brave as a tiger recovering particles.Press table 10 dosage gastric infusion 1 time, the filling gastric capacity is 0.3ml/10g, the acetum 0.1ml/10g of the every Mus lumbar injection 0.4% of 1h behind the medicine, recording start turn round body time (incubation period) and each Mus of injection in back 20 minutes turn round the body number of times, the result sees table 11.

Table 11: golden as brave as a tiger recovering particles Dichlorodiphenyl Acetate causes influence (n=10, the X ± S) of mouse writhing

Compare with the normal control group: * P＜0.05, * * P＜0.01, * * * P＜0.001

Compare with the Xiaoyanlidan capsules group: ^△P＜0.05

The result shows that the high, medium and low dose groups of golden as brave as a tiger health obviously prolongs with the body of turning round of normal control group than mice incubation period, turns round the body number of times and obviously reduces, and its action intensity obviously is superior to Xiaoyanlidan capsules.

(4) golden as brave as a tiger recovering particles is to rat bile secretory volume and bilirubinic influence

50 of extracting male Wistar rats, body weight 250g, rat is with 10% urethane (1g/kg) anesthesia, and back of the body position is fixing; Sterilization abdominal part, center vertically cut the osculum of 2cm, find out common bile duct; Separate common bile duct surface tunicle, insert common bile duct with 5 number sword-shaped needles, and fix with vascular clamp; The intestines and stomach resets, and treats that drainage flow picks up counting after stable, behind the drainage flow of record drain 1h; Each group writes down the guiding amount of bile (with 1ml syringe accurate measurement) of 1h behind the medicine, 2h, 3h, 4h then, and presses by table 11 dosage gastric infusion (matched group waits capacity water) ^[2]Middle method is measured the content of bilirubin in the 4h bile total amount.The result sees table 12,13.

Table 12: golden as brave as a tiger recovering particles is to the excretory influence of rat bile (n=10, X ± S)

Compare with matched group: * P＜0.05, * * P＜0.01, * * * P＜0.001;

Compare with cholagogue and eliminating inflammation function of gallbladder promoting capsule: ^△P＜0.05

The result shows: golden as brave as a tiger recovering particles three dose groups all can make choleresis obviously increase, and its choleretic effect obviously is superior to Xiaoyanlidan capsules.

Table 13: to bilirubinic influence in the rat bile (n=10, X ± S)

Compare with matched group: * p＜0.05, * * p＜0.01, * * * p＜0.001;

Compare with the Xiaoyanlidan capsules group: ^△P＜0.05

Find out that from table 13 golden as brave as a tiger recovering particles can obviously increase the content of bilirubin in the bile, and this effect obviously is superior to Xiaoyanlidan capsules.

Seven, in the brief summary experiment; The as brave as a tiger recovering particles of gold is established three dose groups, and its low dosage is equivalent to recommend the clinical equivalent amount approximately, and middle dose groups is 2 times of dose,equivalents; High dose group is 4 times of dose,equivalents, the used dosage equivalence of used dosage of positive drug Xiaoyanlidan capsules and golden as brave as a tiger recovering particles high dose group.Result of the test shows:

1. bacteriostasis: golden as brave as a tiger recovering particles is in the external growth that can obviously suppress staphylococcus aureus, escherichia coli, streptococcus faecalis and Pseudomonas aeruginosa; Can obviously reduce staphylococcus aureus, escherichia coli attack mortality of mice in vivo.Show that golden as brave as a tiger granule has inside and outside bacteriostasis preferably, it has the significant protection effect to the mice of staphylococcus aureus and coli-infection in vivo, and its effect is superior to Xiaoyanlidan capsules.

2. antiinflammatory action: golden as brave as a tiger recovering particles can obviously alleviate mice ear degree and rat paw edema degree; Can obviously suppress the bullate growth of rat granuloma; Show that golden as brave as a tiger recovering particles has good antiphlogistic effects, its action intensity high dose group all obviously is superior to Xiaoyanlidan capsules (P＜0.01), in, the part index number of low agent group in various degree be superior to the positive control medicine.

3. analgesic activity: golden as brave as a tiger recovering particles can obviously improve the threshold of pain of mice to thermostimulation, and its acting duration is longer than Xiaoyanlidan capsules; The body number of times of turning round that can obviously reduce mice prolongs incubation period, and its effect is superior to Xiaoyanlidan capsules.Show that these article have significant analgesia role to thermostimulation and chemical stimulation property pain.

4. choleretic effect: golden as brave as a tiger recovering particles can obviously promote the bile secretion of rat; 1h onset behind the medicine; Effect continues to reach 4h, and content of bilirubin behind the bile secretion total amount of three dose groups and the medicine in the bile and matched group more obviously increase, and its choleretic effect obviously is superior to Xiaoyanlidan capsules.

In sum, golden as brave as a tiger recovering particles has tangible bacteriostasis (body is interior, external), antiinflammatory action, analgesic activity and choleretic effect, and obviously is being superior to the positive drug Xiaoyanlidan capsules aspect antibacterial, analgesia, the function of gallbladder promoting.

Test the acute toxicity testing of the as brave as a tiger recovering particles of 2 gold medals

One, experiment material

The as brave as a tiger recovering particles of gold: concentration 0.64g/ml prepares with distilled water, lot number: 20010405, and the Drug Manufacturing Room of this institute provide.The as brave as a tiger recovering particles adult of gold usual amounts: Coming-of-Age Day clothes granule 30g (divide clothes three times, each 1 bag, every bag of 10g), the 1g granule is equivalent to crude drug amount 3.05g, and a day clothes 30g granule is equivalent to crude drug amount 91.5g, and promptly 0.428g/kg is equivalent to 1.305g crude drug/kg.

Kunming mouse: Shandong University's Experimental Animal Center, I level animal, numbering: No. 200001002, Shandong kinoplaszm word.

Two, experimental technique and result

Can't measure LD50 through prerun, survey its maximum dosage-feeding so change.Get 20 of healthy Kunming mouses; Body weight 20.53 ± 1.34g; Male and female half and half, a bu three times (each 0.8ml/20g) is irritated stomach behind the fasting 12h, and Cmax is the golden as brave as a tiger recovering particles 76.8g/kg of 0.64g/ml; Observed 7 days continuously, note diet, activity, the defecation of observed and recorded animal and have or not situation such as death.

Experiment shows: after irritating the as brave as a tiger recovering particles of stomach gold to animal, mice generally in order, hair color is bright and clean, diet is drained the no abnormality seen phenomenon.Observed 7 days continuously, the weight of animals increases, none death.See table 14.

Table 14: the acute toxicity testing of golden as brave as a tiger recovering particles

Three, brief summary

Mice is given maximum volume; Cmax was irritated the as brave as a tiger recovering particles 76.8g/kg of stomach gold on 1st, and this dosage is about 179 times of its clinical dosage (0.4286g/kg); Do not see that acute toxic reaction appears in mice; Show this medicine to the maximum tolerated dose of mouse stomach more than 76.8g/kg, be equivalent to crude drug 234.24g/kg, its usual amounts of clinical practice is safe.

Test the long term toxicity test of the as brave as a tiger recovering particles of 3 gold medals

One, experiment material

Gold as brave as a tiger recovering particles: concentration 0.64g/kg, the Drug Manufacturing Room of this institute provide, lot number: 20010405; The as brave as a tiger recovering particles adult of gold usual amounts: every day 3 times; Each 1 bag, the 10g/ bag, the 1g granule is equivalent to the 3.05g crude drug approximately; Adult's total particle consumption is 30g/70kg=0.429g/kg=1.308g crude drug/kg, below all shows with the product particle scale.When irritating stomach with distilled water diluting to desired concn, the time spent shakes up.

The Wistar rat: Shandong University's Experimental Animal Center provides, I level animal, the quality certification number: No. 200001003, Shandong kinoplaszm word.

Instrument: AU-400 automatic biochemistry analyzer, Japan, Olymps Olympus.

AC-970 automatic hemacytometer Sweden.

Reagent: each test kit is all available from Jinan City's epidemic prevention station (eastern bowl biotech firm product)

Two, experimental technique

Get 160 of healthy Wistar rats, in age in 5-6 week, about body weight 60g, male and female half and half are observed before the experiment and are adapted to a week, divide four groups at random: blank group, the high, medium and low dose groups of golden as brave as a tiger recovering particles.Each 20 of every group of male and female, sub-cage rearing, 5 in every cage.The high, medium and low dose groups of the as brave as a tiger recovering particles of gold is pressed 21.4g/kg, 10.7g/kg, 5.35g/kg dosage gastric infusion respectively; Irritating gastric capacity is the 2ml/100g body weight; The water of capacity such as blank group filling stomach; (high dose group administration every day 2 times) respectively organized continuous gastric infusion 6 months, and diet, activity and defecation that experimental period notes observing animal have no abnormal.Claim 1 body weight in per 10 days, in time adjust dosage according to body weight simultaneously.Tested the 45th day and 135 days matched groups and high dose are got 10 animals at random, get blood, survey routine blood test and biochemistry, observe the animal liver and kidney function through jugular vein; Test the 90th day every group get at random 10 (male and female half and half), the 180th day every group get 20 animals (male and female half and half) at random, it is biochemical to survey blood, routine urinalysis and blood, dissects each Mus after getting blood; Core, internal organs such as liver, spleen, lung, kidney, adrenal gland, thymus, brain, testis, epididymis, uterus, ovary; Calculate its organ coefficient, and carry out pathologic finding through 10% formalin fixed, experimental result is by t check carrying out statistical disposition; Remaining animal continues to raise 1 month, repeats above experimental check.

Three, experimental result

(1) to the influence of rat ordinary circumstance

Experimental session is respectively organized the diet, movable good of rat, and the hair color light does not have diarrhoea, eye, ear, nose, oral cavity, the no abnormal secretions of external genital.Gastric infusion is 6 months continuously, and none is poisoned to death animal, and weight increase is seen table 15 to the influence of body weight.

Table 15: to the influence of rat body weight (g, n=40, x ± s)

Each group and the relatively more equal P of matched group＞0.05

(2) rat blood is learned the influence of index

The rat administration is in the time of 45 days, 90 days, 135 days, 180 days, and it is biochemical that have a blood test routine and blood of blood was got in drug withdrawal in 12 hours, and the result sees table 16 to table 23.

Table 16: the variation (n=10, the X ± S) that test 45 day rat routine blood tests

	Matched group	High dose group
			Rbc(10 ¹²/L))	7.17±0.68	6.91±0.59
HB(g/L)	143.4±11.16	139.4±9.38
			PLT(10 ⁹/L)	283.3±101.5	349.6±62.15
WBC(10 ⁹/L)	11.36±3.75	11.99±3.73
			L％	89.42±5.49	91.55±21.53
M％	7.08±3.34	5.81±1.37
			G％	3.50±2.24	2.59±0.78

Table 17: test the biochemical variation of the 45th day rat blood (n=10, X ± S)

	Matched group	High dose group
			AST(Iu/L)	157.5±57.5	146.1±49.8
ALT(IU/L)	41.7±15.6	34.1±9.2
			ALP(IU/L)	136.4±60.6	140.5±66.4
TP(g/L)	53.85±14.96	54.73±9.91
			ALB(g/l)	27.6±6.3	30.27±4.8

BUN(mmol/L)	6.43±1.34	6.17±1.21
			Cr(umol/L)	70.4±18.4	62.6±11.6
Tbil(U)	4.31±1.75	4.92±1.92
			Glu(mmol/L)	4.2±1.4	3.3±1.6
TC(mmol/L)	1.16±0.28	1.18±0.78

From table 16, table 17, find out, administration 45 days, high dose group routine blood test, blood biochemistry relatively do not have significant change with matched group.

Table 18: the variation (n=10, the X ± S) that test 90 day rat routine blood tests

	Matched group	High dose group	Middle dose groups	Low dose group
					Rbc(10 ¹²/L))	6.62±0.58	6.52±0.63	6.72±0.35	6.65±0.65
HB(g/L)	144.6±11.56	149.0±5.9	144.1±1.6	143.0±15
					PLT(10 ⁹/L)	342.9±121.1	383.7±145.9	398.3±98.8	344.8±68.8
WBC(10 ⁹/L)	10.23±3.23	7.17±2.86	7.58±2.48	7.23±2
					L％	95.2±0.96	95.95±1.8	95.78±1.57	94.5±3.4
M％	3.54±0.69	2.56±1.48	2.92±1.2	3.2±1.6
					G％	1.29±0.41	1.49±0.50	1.30±0.42	2.29±2.31

Compare P＞0.05 with matched group

Table 19: test the biochemical variation of the 90th day rat blood (n=10, X ± S)

	Matched group	High dose group	Middle dose groups	Low dose group
					AST(IU/L)	104.5±29.7	85.2±26.8	91.6±29.7	100±29.7
ALT(IU/L)	35.1±1.2	32.1±21.2	34±11.3	33.4±7.7
					ALP(IU/L)	141.6±77.6	130.2±83.5	110±39.8	120.2±26.4
TP(g/L)	49.01±15	46.97±20.7	505±11.9	53.2±14.3
					ALB(g/L)	25.5±7.5	24.53±10.0	26.1±5.1	28.5±6.9
BUN(mmol/L)	5.0±1.2	5.14±1.41	4.8±0.7	4.9±1.2
					Cr(umol/L)	64.5±17.9	56.26±14.86	56.1±10.1	66.96±15.7
Tbil(umol/L)	2.9±1.4	2.88±1.65	3.64±2.5	2.9±0.9
					Glu(mmol/L)	4.2±1.7	3.7±1.9	3.7±1.2	4.2±2.2
TC(mmol/L)	0.9±0.3	0.92±0.3	0.9±0.22	0.98±0.29

Compare P＞0.05 with matched group

Found out administration 90 days from table 18, table 19, the routine blood test of each administration group of rat, blood biochemistry and matched group are than no significant change.

Table 20: the variation (n=10, the X ± S) that test the 135th day rat routine blood test

	Matched group	High dose group
			Rbc(10 ¹²/L))	6.7±0.2	7.1±0.3
HB(g/L)	145.4±5.0	149.6±5.7
			PLT(10 ⁹/L)	399.8±154.0	413.8±50.9
WBC(10 ⁹/L)	9.84±5.3	9.99±3.0
			L％	94.8±1.5	94.1±2..5
M％	3.7±1.0	4.33±1.9
			G％	1.44±0.5	1.55±0.66

Compare P＞0.05 with matched group

Table 21: the variation of administration 135 day rat blood biochemistry (n=10, X ± S)

	Matched group	High dose group
			AST(IU/L)	104.5±29.7	85.2±26.8
ALT(IU/L)	35±11.17	32.1±12.22
			ALP(IU/L)	141.6±77.6	130.2±83.5
TP(g/L)	49.01±15.3	47±20.7
			ALB(g/L)	25.5±7.5	24.5±10
BUN(mmol/L)	4.96±1.15	5.14±1.41
			Cr(umol/L)	64.48±17.88	56.26±14.86
Tbil(umol/L)	2.93±1.45	2.88±1.65
			Glu(mmol/L)	4.21±1.66	3.75±1.86
TC(mmol/L)	0.92±0.33	0.92±0.3

Compare with matched group: P＞0.05

Table 20, table 21 find out that administration is in the time of 135 days, and routine blood test of high dose group rat and blood are biochemical to have no significant change with matched group

Table 22: the variation (n=20, the X ± S) that test the 180th day rat routine blood test

Compare P＞0.05 with matched group

Table 23: test the biochemical variation of the 180th day rat blood (n=20, X ± S)

Compare P＞0.05 with matched group

Find out from table 22, table 23, administration 180 days, the routine blood test of each administration group, blood biochemistry and matched group are than equal no significant difference.

(3) influence of rat urine

Rat administration 90 days, 180 days, each group is respectively got 10 male and female half and half of animal, stays 12 urines, and water is can't help in fasting, measures relevant index, and the result sees table 24.

Table 24: the administration influence to rat urine in 90 days, 180 days (n=10, x ± s)

Find out from table 24, administration 90 days, 180 days, the urine of each administration group has no significant change with the matched group ratio.

(4) pathological anatomy of the main histoorgan of rat is checked

Rat administration 90 days is got 10 for every group, and administration 180 days is got 20 (male and female half and half) for every group, gets to put to death behind the blood and dissects, and cutting off the inspection of abdominal part and thoracic cavity has ascites pleural fluid etc. unusual.Core then, organ such as liver, spleen, lung, kidney, adrenal gland, brain, thymus, stomach, intestinal, testis, uterus, epididymis, ovary; Perusal has no abnormal, and carries out pathological examination with formalin fixed, and main organs is weighed; Calculate organ coefficient, the result is following:

90 days and 180 days pathological replacements:

The heart: inspection substantially, it is all no abnormal that each organizes the cardiac shape size, smooth surface, tangent plane does not have congestion, and chambers of the heart size is all normal.

Microscopy: 90 days, 180 days administration groups and matched group endocardium are all smooth, and muscle fiber is clear, except that between the individual animal cardiac muscle fiber the mild hyperaemia, and no abnormality seen.Liver: inspection substantially, it is all no abnormal that each organizes form size color and luster, smooth surface, tangent plane matter is soft.

Microscopy: administration was respectively organized the lobules of liver clear in structure in 90 days, 180 days, and cell is arranged with rule, no degeneration, necrosis and proliferation of fibrous tissue, and sinus hepaticus does not have expansion, and the portal area structure is no abnormal, is the normal liver tissue structure.

Spleen, lung: inspection substantially, each organizes the gross examination of skeletal muscle Non Apparent Abnormality, the spleen clear-cut margin, tunicle is complete, smooth surface; The lung surface is oozed out with hyperemia etc. unusual.

Microscopy: 90 days, 180 days each administration group, excess syndrome matter red pulp, white pulp and marginal zone three parts are clear and legible, and blood sinus does not have obvious expansion, does not see pathological change; It is clear that each organizes alveolar structure, the no abnormal secretions of intracavity, and bronchioles and interstitial lung do not have obvious cell infiltration.

Kidney: inspection substantially, it is all normal that each organizes outward appearance, and peplos is complete, and tangent plane cortex, medullary substance are demarcated clear.

Microscopy: 90 days, 180 days each administration group glomerule sizes, number, clear in structure; Proximal convoluted tubule free surface brush border mays be seen indistinctly, and matter blood vessel mild hyperaemia between the individual animal kidney, basement membrane do not have and thicken; Spherical no abnormal, with normal control group nephridial tissue structural similarity.The adrenal gland: inspection substantially, medication and contrast body of gland form are no abnormal, and the tangent plane periphery is greyish white, and is middle yellow, the soft exquisiteness of matter.

Microscopy: each group was not seen obvious hypertrophy and atrophy in 90 days, 180 days, and cellular morphology is no abnormal, and glomerular zone, zona fasciculata, reticular zone clear in structure are no abnormal.

Thymus: inspection substantially, each administration group and matched group body of gland form zero difference.

Microscopy: matched group thymus essence is separated into many incomplete lobules by connective tissue, and cortex and medullary substance obviously can be distinguished in the lobule, is the normal structure structure.It is all similar with matched group that all the other respectively organize organizational structure.

Stomach, intestinal: inspection substantially, stomach is respectively organized mucous membrane surface does not have ulcer, and each intestinal segment is not seen obviously unusual.

Microscopy: 90 days, 180 days medication groups and matched group coat of the stomach divide four layers, and wherein mucous layer is thicker, and mucosal epithelium is complete, and the fundic gland chief cell, parietal cell is clear can distinguish that each group is not all seen pathological change.

Testis: inspection substantially, it is normal that each organizes outward appearance, and peplos is complete.

Microscopy: the matched group convoluted seminiferous tubule is arranged in order, and spermatogenic cells at different levels are well arranged in the pipe, and structure is normal, and the spermatid of cluster is arranged in the official jargon, is the normal testis organizational structure, and each administration group is similar with the matched group organizational structure.

Epididymis: inspection substantially, each group is not seen obviously unusual.

Microscopy: epididymal duct is made up of simple cuboidal epithelium, and agglomerating mature sperm cell is arranged in the official jargon, and each organizes equal no abnormality seen.

Brain: inspection substantially, cerebral tissue does not have congestion and edema.

Microscopy: the cerebral cortex clear in structure can distinguish that the clearest with awl cellular layer and ganglion-cell layer structure, each organizes equal no abnormality seen.

Uterus: inspection substantially, uterus outward appearance no abnormality seen.

Microscopy: the matched group endometrium is complete, and intimal epithelium is a simple columnar epithelium, and the single tube body of gland that is dispersed in is arranged in the lamina propria, and flesh layer and placenta percreta do not have cell infiltration, is the normal uterine tissue structure.It is similar with matched group that all the other respectively organize the uterine cancer cell structure.Ovary: inspection substantially, the ovary color is dark red, surperficial Fructus Mori shape;

Microscopy: each administration group and matched group ovary are formed by the follicle of growing different times, corpus luteum, and be more than 8 layers, no hemorrhage and downright bad than large follicle endoparticle cell, do not see pathological change.

Table 25: the dirty body ratio (g/100g, n=10, the X ± S) that test the 90th day rat main organs

	Matched group	High dose group	Middle dose groups	Low dose group
					The heart	0.318±0.041	0.335±0.025	0.31±0.02	0.34±0.054
Liver	2.827±0.353	3.045±0.901	2.894±0.419	2.804±0.413
					Spleen	0.306±0.15	0.287±0.111	0.267±0.098	0.444±0.052
Lung	0.649±0.182	0.602±0.116	0.596±0.104	0.645±0.119
					Kidney	0.566±0.061	0.568±0.058	0.585±0.037	0.566±0.049
The adrenal gland	0.021±0.01	0.024±0.007	0.019±0.008	0.024±0.01
					Thymus	0.124±0.028	0.155±0.049	0.153±0.051	0.124±0.056
Brain	0.587±0.08	0.563±0.075	0.572±0.089	0.574±0.073
					The uterus	0.263±0.139	0.203±0.041	0.165±0.181	0.245±0.051
Testis	0.928±0.104	0.854±0.091	1.018±0.197	0.952±0.316
					Epididymis	0.407±0.024	0.408±0.086	0.397±0.087	0.416±0.069
Ovary	0.037±0.009	0.04±0.013	0.025±0.027	0.042±0.011

Table 26: the dirty body ratio (g/100g, n=20, the X ± S) that test the main organs of the 180th day rat

	Matched group	High dose group	Middle dose groups	Low dose group
					The heart	0.333±0.037	0.33±0.031	0.353±0.165	0.314±0.04
Liver	3.405±0.851	3.912±0.742	3.455±0.378	3.617±0.674
					Spleen	0.255±0.062	0.211±0.047	0.215±0.06	0.254±0.077
Lung	0.566±0.147	0.61±0.203	0.531±0.079	0.55±0.114
					Kidney	0.698±0.209	0.699±0.111	0.699±0.1	0.691±0.363
The adrenal gland	0.023±0.008	0.021±0.008	0.019±0.007	0.018±0.007
					Thymus	0.119±0.034	0.105±0.031	0.104±0.017	0.122±0.06
Brain	0.547±0.077	0.544±0.092	0.572±0.07	0.513±0.122
					The uterus	0.266±0.089	0.228±0.071	0.226±0.106	0.406±0.124
Testis	1.033±0.281	0.916±0.207	0.966±0.162	0.579±0.627

Epididymis	0.431±0.111	0.361±0.073	0.34±0.067	0.221±0.231
					Ovary	0.048±0.011	0.038±0.013	0.051±0.006	0.04±0.012

Compare with matched group: P＞0.05

Experimental result shows that golden as brave as a tiger recovering particles does not have obvious damage to the rat main organs, and rat main organs coefficient is not had obvious influence.

(5) rat recovers experiment

Each group residue animal drug withdrawal continues to raise one month, and it is biochemical to get have a blood test routine and blood of blood, and the result sees table 27, table 28, put to death core behind the animal, organs such as liver, spleen, lung, kidney, adrenal gland, thymus, brain carry out pathological examination, and calculate each organ coefficient.See table 29.

Table 27: the conventional influence of rat serum after 30 days (n=10, X ± S) recover are raised in drug withdrawal

	Matched group	High dose group	Middle dose groups	Low dose group
					Rbc(10 ¹²/L))	5.65±0.91	5.5±0.57	6.06±0.35	6.16±0.73
HB(g/L)	127.3±20.13	124.5±10.05	136.9±7.72	139.4±16.57
					PLT(10 ⁹/L)	465.7±75.94	483.1±82.84	493.5±115.48	464.4±53.61
WBC(10 ⁹/L)	10.92±2.6	9.77±2.44	10.43±3.72	9.92±2.38
					L％	84.85±7.78	82.49±4.88	79.48±5.99	84.12±4.3
M％	10.24±4.33	13.22±3.12	13.9±4.53	11.2±3.24
					G％	4.91±3.95	4.29±1.85	6.6±1.76	4.68±1.45

Find out that from table 27 drug withdrawal recovered 30 days, the routine blood test of each administration group rat and matched group are than there are no significant difference.

Table 28: the influence (n=10, the X ± S) that drug withdrawal recover are raised blood biochemistry of rats after 30 days

	Matched group	High dose group	Middle dose groups	Low dose group
					AST(IU/L)	103.2±30.6	84.9±26.7	93.5±30.61	106.2±35.15
ALT(IU/L)	28.8±11.2	42.3±17.7	30.8±11.9	33.4±7.72
					ALP(IU/L)	142.6±77.8	157.5±66.96	102.6±67.41	122.1±33.04
TP(g/L)	49.8±17.7	48.39±21.32	45.32±6.52	50.97±11.62
					ALB(g/L)	22.7±7.4	27.11±8.07	26.09±5.12	28.59±6.83
BUN(mmol/L)	4.92±1.15	5.05±1.55	5.04±1.03	4.92±1.3
					Cr(umol/L)	55.86±11.45	58.59±13.02	65.76±16.76	67.03±15.68
Tbil(umol/L)	2.83±1.23	2.72±1.81	3.51±1.3	3.35±2.34
					Glu(mmol/L)	3.89±1.91	3.89±2.28	4.41±1.37	3.71±1.28
TC(mmol/L)	1.09±0.38	0.83±0.32	0.95±0.21	1.00±0.29

Parameters and matched group be P＞0.05 relatively all

Find out that from table 28 drug withdrawal recovered 30 days, the blood biochemistry that rat is respectively organized in administration and matched group are than there are no significant difference.

The pathological tissue inspection shows that the organizational structure of drug withdrawal each administration group main organs after 30 days is similar with matched group, does not have obvious pathological change.

Table 29: to the influence of the convalescent organ coefficient of rat (g/100g, n=10, X ± S)

	Matched group	High dose group	Middle dose groups	Low dose group
					The heart	0.263±0.052	0.256±0.047	0.285±0.041	0.282±0.069
Liver	2.222±0.466	2.464±0.492	2.5250.44	2.473±0.457
					Spleen	0.17±0.063	0.186±0.031	0.22±0.064	0.354±0.547
Lung	0.413±0.113	0.471±0.124	0.506±0.088	0.412±0.058
					Kidney	0.445±0.077	0.472±0.087	0.505±0.056	0.474±0.08
The adrenal gland	0.0190.005	0.033±0.049	0.018±0.006	0.019±0.004

Thymus	0.091±0.019	0.085±0.021	0.096±0.044	0.102±0.032
					Brain	0.42±0.014	0.439±0.062	0.449±0.048	0.43±0.042
The uterus	0.201±0.031	0.161±0.077	0.309±0.141	0.165±0.051
					Testis	0.88±0.194	0.859±0.132	1.005±0.131	0.829±0.15
Epididymis	0.345±0.026	0.354±0.052	0.326±0.057	0.33±0.021
					Ovary	0.04±0.01	0.034±0.006	0.042±0.01	0.036±0.007

Each group is P＞0.05 relatively

Experimental result shows that the rat drug withdrawal was raised after 30 days, and the rat serum of matched group and the high, medium and low dose groups of golden as brave as a tiger recovering particles is conventional, blood is biochemical and the equal Non Apparent Abnormality of histopathological examination.Show: after the as brave as a tiger recovering particles drug withdrawal of prolonged application gold, no delayed toxicity reaction.

Four, conclusion

Irritated the as brave as a tiger recovering particles of stomach gold continuous 180 days every day for rat; Its high dose 21.4g/kg reaches 50 times of clinical consumption; To the general situation of rat, blood, routine urinalysis, the equal non-toxic reaction of hepatic and renal function and main organs; Show that the heavy dose of prolonged application of golden as brave as a tiger recovering particles do not have the overt toxicity reaction, its usual amounts of clinical practice is safe.

Attach: clinical trial is with the raw material (medical material) of golden as brave as a tiger recovering particles and the quality standard (draft) of finished product

One, quality of medicinal material draft standard

1. Rhizoma Polygoni Cuspidati (Rhizoma polygoni cuspidati): these article are dry rhizome and the root of polygonaceae plant Rhizoma Polygoni Cuspidati Polygonum cuspidatum Sieb.et Zucc..Its quality should meet " the pertinent regulations under the 194th page of Rhizoma Polygoni Cuspidati item of version in 2010 of Chinese pharmacopoeia.Emodin content is surveyed by the method in this standard in the Rhizoma Polygoni Cuspidati in addition, should be not less than 1.5%.

2. Herba Artemisiae Scopariae (Herba artemisiae scopariae): these article are the dry aerial parts of feverfew BINHAO Artemisia scoparia Waldst.et kit. or Herba Artemisiae Scopariae Artemisia capillaris Thunb..Its quality should meet " the pertinent regulations under the 223rd page of Herba Artemisiae Scopariae item of Chinese pharmacopoeia version in 2010.

3. Radix Bupleuri (Radix bupleuri): these article are the dry root of umbelliferae bupleurum Bupleurum chinense DC. (being Radix Bupleuri).Its quality should meet " the pertinent regulations under the 263rd page of Radix Bupleuri item of version in 2010 of Chinese pharmacopoeia.

4. Herba Lysimachiae (Herba lysimachiae): these article are the dry herb of Primulaceae plant Lysimachia christinae Hance Lysimachia christinae Hance.Its quality should meet " the pertinent regulations under the 204th page of Herba Lysimachiae item of version in 2010 of Chinese pharmacopoeia.

5. Fructus Gardeniae (Fructus gardeniae): these article are the dry mature fruit of Maguireothamnus speciosus Fructus Gardeniae Gardenia jasminoides Ellis.Its quality should meet " the pertinent regulations under the 231st page of Fructus Gardeniae item of version in 2010 of Chinese pharmacopoeia.

6. Cortex Fraxini (Cortex fraxini): these article are dry branch skin or the dried bark of Oleaceae plant fraxinus rhynchophylla Hance Fraxinus rhynchophylla Hance., Chinese ash Fraxinus chinensis Roxb., sharp leaf Chinese ash Fraxinus stylosa Lingelsh..Its quality should meet " the pertinent regulations under the 254th page of Cortex Fraxini item of version in 2010 of Chinese pharmacopoeia.

7. the Radix Pulsatillae (Radix p μ lsatillae): these article are the dry root of cohosh Radix Pulsatillae P μ lsatilla chinensis (Bge.) Regel.Its quality should meet " the pertinent regulations under the 96th page of Radix Pulsatillae item of Chinese pharmacopoeia version in 2010.

8. Radix Curcumae: these article are the dried root of zingiberaceous plant RADIX CURCUMAE Curcuma wenyujin Y.H.Chen et C.Ling, Rhizoma Curcumae Longae Curcuma longa L., Guangxi zedoary Curcuma kwangsiensis S.G.Lee et C.F.Liang or Rhizoma Curcumae Curcuma phaeocaulis Val..Its quality should meet " the pertinent regulations under the 193rd page of Radix Curcumae item of Chinese pharmacopoeia version in 2010.

9. Rhizoma Corydalis (Rnizoma corydalis): these article are the dry tuber of bloodroot Corydalis yanhusuo W.T.Wang.Its quality should meet " the pertinent regulations under the 130th page of Rhizoma Corydalis item of Chinese pharmacopoeia version in 2010.

10. Fructus Crataegi (Fructus crataegi): these article are the dry mature fruit of rosaceous plant Fructus Pyri Pashiae Crataegus pinnatifida Bge.var.major N.E.Br. or Fructus Crataegi Crataegus pinnatifida Bge..Its quality should meet " the pertinent regulations under the 29th page of Fructus Crataegi item of Chinese pharmacopoeia version in 2010.The used medical material of this kind is a Fructus Crataegi (parched to brown), and it is concocted by " an appendix II of Chinese pharmacopoeia version in 2010 the D medicinal material processing general rule method of frying is concocted.

11. Radix Vladimiriae (Radix vladimiriae): these article are the dry root of feverfew Radix Vladimiriae Vladimiria so μ liei (Franch.) Ling or gray wool Radix Vladimiriae Vladimiria souliei (Franch.) Ling var.cineroa Ling.Its quality should meet " the pertinent regulations under the 33rd page of Radix Vladimiriae item of Chinese pharmacopoeia version in 2010.

Two, the quality standard draft of finished product

[method for making] takes by weighing above 11 flavor stock of drugs decoction pieces in the prescription ratio, and the Rhizoma Corydalis micronizing is a micropowder, and Rhizoma Polygoni Cuspidati, Cortex Fraxini, Fructus Crataegi are with 75% ethanol extraction 3 times, 2 hours first time; Second and third time respectively is 1.5 hours, filters, and merges 3 times alcohol extract; Decompression recycling ethanol also is concentrated into the runny plaste that does not have alcohol flavor (relative density 1.15～1.20,60 ℃ of surveys), the medicinal liquid of thin up to 1.08～1.15; Heated and boiled 10 minutes, fully mixing filters while hot; Medicinal residues merge washing liquid in filtrating with hot wash 2 times, and water liquid is evaporated to the thick paste that relative density is 1.30～1.35 (60 ℃ of surveys); Herba Artemisiae Scopariae, Radix Bupleuri, Radix Curcumae, Radix Vladimiriae are extracted volatile oil, and are encapsulated with for use with powder-beta-dextrin, leach the water liquid that extracts behind the volatile oil in addition device collect medicinal residues and Herba Lysimachiae, Fructus Gardeniae, Radix Pulsatillae merging, decocte with water 2 times; 2 hours for the first time, 1.5 hours for the second time, filter, merge the water liquid behind 2 decocting liquid and the said extracted volatile oil; Being evaporated to relative density is the medicinal liquid of 1.10～1.12 (60 ℃ of surveys), under fully stirring, slowly adds 1.5 times of 95% ethanol (it is 57% that medicinal liquid contains the alcohol amount), adds continued and stirs 20 minutes, makes deposition; Left standstill 48 hours, and filtered, decompression recycling ethanol also is concentrated into the thick paste that relative density is 1.30～1.35 (60 ℃ of surveys), merges with above-mentioned alcohol extraction cream; Add the Rhizoma Corydalis micropowder, add dextrin 30g, mixing, vacuum drying by each recipe quantity thick paste; Pulverize, add β-CD inclusion complex and stevioside 1.5g, mixing is granulated; Drying is processed the 100g granule, by every bag of 10g packing, promptly gets.

[character] these article are brown granular, feeble QI, and it is little sweet to distinguish the flavor of, little hardship.

These article 5g is got in [discriminating] (1), and porphyrize adds kieselguhr ± 3g, mixes thoroughly, the 100ml that adds diethyl ether, and water-bath refluxed 2 hours; Filter, after residue volatilizes, add methanol 100ml again, refluxed 2 hours, filter; Reclaim methanol to doing, residue adds water 30ml dissolving, with water saturated n-butanol extraction 3 times (30,30,30ml); Merge n-butyl alcohol liquid, with ammonia solution washing 2 times (30,30ml), discard ammonia solution, again with water washing 2 times (40; 40ml), discard water liquid, n-butyl alcohol liquid evaporate to dryness, residue add methanol 2ml makes dissolving, as need testing solution.Other gets Radix Bupleuri control medicinal material coarse powder 2g, the same medical material contrast liquid of processing.According to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2010 B) test, draw each 4 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate; With ethyl acetate-95% alcohol-water (8: 2: 1) is developing solvent; Launch, take out, dry; Spray is with 10% sulphuric acid ethanol liquid, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the principal spot of same color.

(2) get these article 4g, porphyrize adds kieselguhr 3g, mixes thoroughly, puts in the apparatus,Soxhlet's; The 100ml that adds diethyl ether, reflux, extract, 3 hours, volatilize solvent after, add ethyl acetate 100ml, reflux, extract, 2 hours; Filter, reclaim solvent and do near, residue adds methanol 2ml makes dissolving, as need testing solution.Other gets the jasminoidin reference substance, adds methanol and processes the solution that every 1ml contains 1mg, as reference substance solution.According to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B) test, draw need testing solution 5 μ l, reference substance solution 3 μ l, put respectively on same silica gel g thin-layer plate; With ethyl acetate-acetone-formic acid-water (10: 6: 2: 0.25) be developing solvent; Launch, take out, dry; Spray is with 10% sulphuric acid ethanol, and hot blast blows to clear spot.In the test sample chromatograph with the corresponding position of reference substance chromatograph on, show the speckle of same color.

(3) get these article 5g, porphyrize adds kieselguhr 3g, mixes the 50ml that adds diethyl ether, reflux, extract, 2 hours thoroughly; Put coldly, filter, residue volatilizes, and adds 95% ethanol 100ml, and reflux, extract, 3 hours is taken off; Put coldly, filter, be recycled to the greatest extent, add 5% sodium carbonate 40ml dissolving, transfer PH to 2, with ethyl acetate extraction 3 times (40 with dilute hydrochloric acid; 30,30ml), merge extractive liquid, reclaims solvent and does near, and residue adds 95% ethanol 2ml makes dissolving, as need testing solution.Other gets the aesculetin reference substance and processes the solution that every 1ml contains 1mg, as reference substance solution.According to thin layer chromatography (2000 editions one appendix VI B of Chinese Pharmacopoeia) test, draw each 3 μ l of above-mentioned need testing solution and reference substance solution, put respectively on same silica gel g thin-layer plate; (3: 4: 2: 1) be developing solvent, expansion was taken out with toluene-ethyl acetate-ethanol-formic acid; Dry; Put under the ultra-violet lamp (365nm) and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the fluorescence speckle of same color.

(4) get these article 5g, porphyrize adds kieselguhr 5g and mixes thoroughly, puts in the apparatus,Soxhlet's 100ml that adds diethyl ether, reflux, extract, 1 hour; After drying, add methanol 100ml, reflux, extract, 5 hours is put coldly, filters, and reclaims methanol to the greatest extent; Residue adds water 30ml, and slight fever makes dissolving, with water-saturated n-butanol extract 3 times (40,30,30ml); Merge n-butyl alcohol liquid, with ammonia solution washing 2 times (50,50ml), discard ammonia solution, again with water washing 2 times (40; 40ml), discard water liquid, n-butyl alcohol liquid evaporate to dryness, residue add methanol 5ml makes dissolving, as need testing solution.Other gets Radix Pulsatillae medical material 2g, the same Radix Pulsatillae medical material contrast liquid of processing.According to thin layer chromatography (2000 editions one appendix VI B of Chinese Pharmacopoeia) test, draw need testing solution 5 μ l, control medicinal material solution 3 μ l; Putting respectively on same silica gel g thin-layer plate, is developing solvent with the upper strata liquid of n-butyl alcohol-acetic acid-water (4: 1: 5), launches; Take out; Dry, spray is with 10% sulphuric acid ethanol liquid, and it is clear that hot blast blows to the speckle colour developing.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on show the principal spot of same color.

(5) get these article 5g, porphyrize adds kieselguhr 5g and mixes thoroughly, adds strong aqua ammonia 3ml and mixes thoroughly, airtight 0.5 hour; The 80ml that adds diethyl ether, merceration 2 hours filters, and residue washs with a small amount of ether; Merge ether solution, reclaim solvent and do near, residue adds dehydrated alcohol 2ml makes dissolving, as need testing solution.Other gets the tetrahydropalmatine reference substance and adds dehydrated alcohol and process the solution that every 1ml contains 1mg, as reference substance solution.According to thin layer chromatography (2000 editions one appendix VI B of Chinese Pharmacopoeia) test, draw each 5 μ l of above-mentioned two kinds of solution, put respectively on same 1%NaOH silica gel g thin-layer plate, be developing solvent with petroleum ether (60～90 ℃)-ethyl acetate (2: 1.5); Launch, take out, dry; Smoked with iodine vapor to clear spot, take out, in air, wave the iodine that adsorbs on the most plate after; Put under the uviol lamp (365nm) and inspect, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the fluorescence speckle of same color.

(6) get these article granule 6.0g, add kieselguhr 3.0g, grind well, add the 80ml ether, extracted 2 hours, extracting solution reclaims ether to doing, and residue is used anhydrous alcohol solution, is settled in the 2ml measuring bottle, as test sample liquid.Other gets the ursolic acid reference substance, processes the solution that every ml contains ursolic acid 0.5mg with dehydrated alcohol, as reference substance solution; According to thin layer chromatography (" an appendix VI of Chinese pharmacopoeia version in 2000 B) test, draw need testing solution and reference substance solution 5 μ l respectively, put on same silica gel g thin-layer plate; With cyclohexane extraction-ethyl acetate-glacial acetic acid (9: 3: 0.25) is developing solvent, launches, and takes out; Dry, spray is with 10% sulphuric acid ethanol liquid, and hair dryer is heated to clear spot; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

[inspection] should meet each item regulation (an appendix I of Chinese Pharmacopoeia version in 2000 C) under the granule item.

[assay] got the granule under these article content uniformity item, and porphyrize is got 1.0g, and accurate the title decides, and adds water 50ml, dripping hydrochloric acid 5ml; Add chloroform 60ml again, water-bath refluxed 3 hours, took off, and put coldly, quantitatively was transferred in the separatory funnel, told chloroform solution; 3 times (40,40,30ml) 4 chloroform solutions of merging with water 50ml washing once, discard water liquid to the reuse chloroform extraction; Add anhydrous sodium sulfate 10g, placed 2 hours, filter,, reclaim chloroform to most with the minimum of chloroform washing; Residue adds anhydrous alcohol solution, quantitatively is transferred in the 10ml measuring bottle, adds dehydrated alcohol to scale, shakes up, as need testing solution.Other gets the emodin reference substance, adds methanol and processes the solution that every 1ml contains 0.2mg, as reference substance solution.According to thin layer chromatography (2000 editions one appendix VI B of Chinese Pharmacopoeia) test, draw need testing solution 2 μ l, reference substance solution 2,4 μ l; The cross point is on same 0.3%CMC silica gel g thin-layer plate; With petroleum ether (60～90 ℃)-ethyl acetate-glacial acetic acid (15: 1.5: 1, V/V) for developing solvent, launch; Take out, dry.Scan wavelength X according to thin layer chromatography (an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography scanning) _S=445nm, λ _R=700nm measures test sample trap integrated value and reference substance trap integrated value, calculates, and promptly gets.

These article contain emodin (C ₁₅H ₁₀O ₅) total amount, every bag must not be less than 28mg.

[function with cure mainly] removing damp-heat, depressed liver-energy dispersing and function of gallbladder promoting, regulating QI to relieve pain cures mainly the chronic cholecystitis of damp-heat type.Disease is seen upper right abdomen persistence distending pain, and pain is drawn the shoulder back of the body, companion's sense of heaviness or heating, bitter taste, dry pharynx, nausea and vomiting, constipation etc.

[usage and consumption] is oral, warm boiled water, one time one bag, three times on the one.

[specification] every bag of 10g, 10 bags of every packings.

[storage] sealing is put shady and cool dry place and is preserved.

Need to prove at last, more than all medicines of being adopted of test, do not specify that it is prepared to be embodiment 1 if having.

Claims

1. a Chinese medicine preparation of treating chronic cholecystitis is characterized in that, is processed by following bulk drugs: 25～45 parts of Rhizoma Polygoni Cuspidati, 20～50 parts of Herba Artemisiae Scopariaes; 25～45 parts of Radix Bupleuri, 30～50 parts of Herba Lysimachiaes, 20～40 parts of Fructus Gardeniaes; 20～40 parts of Cortex Fraxinis, 15～35 parts of the Radix Pulsatillaes, 10～30 parts of Radix Curcumaes; 10～30 parts of Rhizoma Corydalis, 10～30 parts of Fructus Crataegis, 5～15 parts of Radix Vladimiriaes.

2. the Chinese medicine preparation of kind treatment chronic cholecystitis according to claim 1 is characterized in that: processed by following bulk drugs: 35 parts of Rhizoma Polygoni Cuspidati, 40 parts of Herba Artemisiae Scopariaes; 35 parts of Radix Bupleuri, 40 parts of Herba Lysimachiaes, 30 parts of Fructus Gardeniaes; 30 parts of Cortex Fraxinis, 25 parts of the Radix Pulsatillaes, 20 parts of Radix Curcumaes; 20 parts of Rhizoma Corydalis, 20 parts of Fructus Crataegis, 10 parts of Radix Vladimiriaes.

3. the Chinese medicine preparation of kind treatment chronic cholecystitis according to claim 1 is characterized in that: processed by following bulk drugs: 30 parts of Rhizoma Polygoni Cuspidati, 45 parts of Herba Artemisiae Scopariaes; 30 parts of Radix Bupleuri, 45 parts of Herba Lysimachiaes, 25 parts of Fructus Gardeniaes; 35 parts of Cortex Fraxinis, 20 parts of the Radix Pulsatillaes, 25 parts of Radix Curcumaes; 15 parts of Rhizoma Corydalis, 25 parts of Fructus Crataegis, 13 parts of Radix Vladimiriaes.

4. the Chinese medicine preparation of kind treatment chronic cholecystitis according to claim 1 is characterized in that: processed by following bulk drugs: 40 parts of Rhizoma Polygoni Cuspidati, 30 parts of Herba Artemisiae Scopariaes; 40 parts of Radix Bupleuri, 35 parts of Herba Lysimachiaes, 35 parts of Fructus Gardeniaes; 25 parts of Cortex Fraxinis, 30 parts of the Radix Pulsatillaes, 15 parts of Radix Curcumaes; 25 parts of Rhizoma Corydalis, 15 parts of Fructus Crataegis, 8 parts of Radix Vladimiriaes.

5. the method for preparing of the Chinese medicine preparation of the described kind treatment of claim 1 chronic cholecystitis is characterized in that, may further comprise the steps:

(1) take by weighing 11 herbal medicine decoction pieces, the Rhizoma Corydalis micronizing is micropowder, and is subsequent use;

(2) Rhizoma Polygoni Cuspidati, Cortex Fraxini, Fructus Crataegi are put in the same extraction pot, add 75% ethanol of 8 times of weight of medical material, reflux, extract, 2 hours; Filter, medicinal residues add 75% ethanol of 6 times of weight again, the same reflux, extract, 2 times, each 1.5 hours; Filter, merge three times alcohol extract, decompression recycling ethanol also is concentrated into the runny plaste of relative density 1.15～1.20, and thin up to relative density is 1.05～1.10 medicinal liquid; Heated and boiled 10 minutes filters while hot, and deposition is with hot wash 2 times; Merge washing liquid in filtrating, be evaporated to relative density and be 1.30～1.35 thick paste, subsequent use;

(3) Herba Artemisiae Scopariae, Radix Bupleuri, Radix Curcumae, Radix Vladimiriae 4 herbal medicines are put in the volatile oil extraction pot, add the water of 10 times of weight of medical material, with steam distillation distillating extracting oil 4 hours, collect volatile oil, and use the powder-beta-dextrin inclusion, and are subsequent use; Leach the water liquid that extracts behind the volatile oil in addition device collect, medicinal residues and Herba Lysimachiae, Fructus Gardeniae, the Radix Pulsatillae merge, decocte with water 2 times, 2 hours first time; 1.5 hours for the second time, filter, merge the water liquid behind 2 decocting liquid and the said extracted volatile oil, be evaporated to relative density and be 1.10～1.12 medicinal liquid; Under fully stirring, slowly add 95% ethanol of 1.5 times of weight of medicinal liquid, stir, left standstill 48 hours; Filter decompression recycling ethanol and to be concentrated into relative density be 1.30～1.35 thick paste

Subsequent use;

(4) thick paste that thick paste that step (2) is prepared and step (3) prepare merges, and it is an amount of to add Rhizoma Corydalis micropowder and dextrin, mixing, and vacuum drying is pulverized, and adds β-CD inclusion complex and an amount of flavoring agent, and mixing is granulated, and drying promptly gets.

6. method for preparing according to claim 5 is characterized in that: in the said step (1), be that the concrete operations of micropowder are with the Rhizoma Corydalis micronizing: get Rhizoma Corydalis, in 50～55 ℃ of oven dry, use super micron mill to pulverize and be micropowder.

7. method for preparing according to claim 5 is characterized in that: in the said step (3), the method for preparing of " collect volatile oil, and use the powder-beta-dextrin inclusion " is specially: get the volatile oil of extraction, and with isopyknic dehydrated alcohol dilution, subsequent use; Take by weighing the β-CD that is equivalent to 8 times of weight of volatile oil again, add entry in the ratio of β-CD: water=1g: 25ml, slight fever makes dissolving, and to keep solution temperature be 35 ℃; Under agitation, slowly splash into the ethanol liquid of volatile oil, add continued and stirred 3 hours; Put 0～4 ℃, leave standstill 12h, sucking filtration; Filter cake is put 40～45 ℃ of dryings, and porphyrize is subsequent use.

8. method for preparing according to claim 5 is characterized in that: in the said step (3), the method for distilling of water decoction-alcohol sedimentation medicine is specially: take by weighing Herba Lysimachiae, Fructus Gardeniae, the Radix Pulsatillae 3 herbal medicines, with 4 flavor medicinal residues merging behind the extraction volatile oil; Add the water of 10 times of amounts, decocted 2 hours, filter; Medicinal residues add 8 times water again, decoct 1.5 hours, filter; Merge the water liquid behind 2 decocting liquid and the said extracted volatile oil, be evaporated to relative density and be 1.10～1.12 medicinal liquid, under fully stirring, slowly add 1.5 times of 95% ethanol and make deposition; Stir, left standstill 48 hours, filter; Decompression recycling ethanol, and to be concentrated into relative density be 1.30～1.35 thick paste, subsequent use.