CN104095904B - A kind of pharmaceutical composition for treating courage relevant disease, preparation method and its usage - Google Patents

Abstract

The invention discloses a kind of pharmaceutical composition for treating courage relevant disease, preparation method and its usage.Composition includes emblic, myrobalan, terminaliae billericae,fructus；By the step such as mixing, decocting, concentration pill or oral liquid is made.Pharmaceutical composition of the present invention is shown in zoopery significantly suppresses normal choleresis effect, and energy conspicuousness suppresses abnormal hypercholia, change biliary tract internal dynamics parameter, reduce gall-bladder and courage overpressure, reduce the resistance of Oddi sphincters, reduce the infringement of stimulation and gastrointestinal mucosa of the bile to the biliary system incision surface of a wound, reach pain of alleviation, promote the effect of functional recovery, suitable for biliary tract dyskinesis, include the treatment of Postcholecystectomy Bile road dyskinesis and courage external form biliary tract dyskinesis；Present invention combination can significantly alleviate the right Upper abdominal pain of recurrent exerbation, upper right abdominal pressure pain, and upper abdomen continues burn feeling, pain after breastbone, and other simultaneous phenomenons, such as belch, sour regurgitation, Nausea and vomiting, anorexia and become thin.

Description

A kind of pharmaceutical composition for treating courage relevant disease, preparation method and its usage

Technical field

The present invention relates to a kind of pharmaceutical composition, preparation method and its usage, especially belongs to treat disease of digestive system Plant drug composition, preparation method and its usage, be particularly used to treating the pharmaceutical composition of courage relevant disease, preparation method and Its purposes.

Background technology

Biliary tract dyskinesis (Biliarydyskinesia) is although refer to the symptom with suspicion for Biliary system diseases, and pass through Various image analysises, do not find that the organic disease at any position of courage system becomes but, such as cholelithiasis, inflammation, tumour【James Toouli Current Treatment Options in Gastroenterology 09/2002；5(4):285- 291.DOI:10.1007/s11938-002-0051-9】.Bile discharge process, it is ingenious by gall-bladder, pipe, OddiShi sphincters Motor adjustment complete, biliary dyskinesia occurs, and to be that normal motor adjustment produces disorderly.Its clinical manifestation and gall-bladder Calculus is closely similar.It is mainly shown as the upper abdomen of recurrent exerbation or right Upper abdominal pain, some patientss can be with nausea and vomiting, can be because Feed greasy food to induce, often continue 2~3h, remission after medication【Brown,M R；Siafakas,CG；Ryan,CK； Pegoli,W；Miller, T L, Biliary Dyskinesia:A Cause of Recurrent Abdominal Pain, Diagnosis By Cck Cholescintigraphy, Relief of Pain After Cholecystectomy, Journal of Pediatric Gastroenterology&Nutrition:October1998-Volume27-Issue4- P470, Annual Meeting of the North American Society for Pediatric Gastroenterology and Nutrition；Orlando,October22-24,1998】,【Tanaka directly shakes:Biliary motility The disease of obstacle should be with diagnosis internal medicine 6, (3):455,1990, Jianming Zhou is translated selected passages, and Hu Ji sparetime schools for adults, Japan medical science introduces 99.Year the 11st Volume o. 11th, page 515】

Cause the factor of biliary tract dyskinesis complicated and interrelated, some factors are particularly important, as choleresis pressure and The resistance of Oddi sphincters is the fluid dynamics parameter such as bile point of hepatic bile an important factor for determining biliary dynamics function The amount of secreting, flow velocity, rhythm, it is closely related with gall-bladder and courage overpressure and biliary tract dyskinesis【Hogan WJ, Geenen JE., Biliary dyskinesia.Endoscopy.1988Aug；20Suppl1:179-83.】,【Chen Shizhu, biliary system motion are adjusted The diagnosis and treatment of section and feature biliary motility exception, World Chin J Digestol2003May；11(5):613-618, the world Chinese digests magazine ISSN1009-3079CN14-1260/R】.

The generation and secretion of normal bile：Bile is continuously generated by liver cell, and common hepatic duct flows out after generation, through choledochus And the duodenum that arrives, or gall-bladder is transferred to by common hepatic duct and is stored in gall-bladder, duodenum is expelled to by gall-bladder again when digestion.Bile And pancreatic juice, intestinal juice carry out chemical digestion together, to enteral chyme.Adult daily secretion of bile about 800-1000ml, The growing amount of bile is relevant with the intake of protein, and high protein diet can generate more bile.Food is in alimentary canal Cause the natural stimulus of choleresis and discharge.High protein diet (yolk, meat, liver) causes bile outflow most, higher fatty acid Or the effect of mixing food is taken second place, and the effect of polysaccharide food is minimum.In bile discharge process, gall-bladder and oddi sphincters When activity typically exhibits the relation, i.e. gallbladder contraction of coordination, oddi sphincter relaxations；On the contrary, during gall-bladder diastole, Oddi is included about Flesh then shrinks【Wang Lin, adjust courage mixture A large for experimental study Liaoning University of TCM of postcholecystectomy reduction choleresis Scholar's paper, 2009-05-01】.Generation of the neural factors to bile, secretion have certain effect.Nerve is received to choleresis and gall-bladder The effect of contracting shows that feeding action or food to stomach, the stimulation of small intestine, can cause lacking for hepatic bile secretion by neural reflex Amount increase, gallbladder contraction are also slightly strengthened, and the efferent pathway of reflection is vagus nerve, cut off both sides vagus nerve, or using courage Alkali energy receptor blocking pharmacon, can block this reaction.Generation of the humoral factor to bile, secretion play an important role.There are a variety of bodies Liquid factor participates in secretion and discharge (l) gastrin of regulation bile：Secretion and smooth muscle of bile vesica of the gastrin at least to liver and gall Contraction has certain stimulation, and it can act on liver cell and gall-bladder by blood circulation；Also gastric acid secretion can first be caused, The latter is remake for duodenal mucosa, causes secretin to discharge and promote hepatic bile to secrete.(2) secretin：Promote pancreatic juice The main effect of element is to stimulate pancreatic secretion, but it also has certain effect for stimulating hepatic bile to secrete.Secretin is mainly made For biliary system rather than act on liver cell.(3) CCK：In protein breakdown products, the material such as hydrochloric acid and fat Under effect, the releasable CCK of work cell in upper part of small intestine mucous membrane, it is drawn by blood circulation excitement smooth muscle of bile vesica Play the strong contraction of gall-bladder.CCK then plays the role of to reduce its tonicity to oddi sphincters, therefore can promote gall-bladder A large amount of discharges of juice.CCK can also stimulate bile duct epithelial cell, make bile flow and HCO₃Secretion increase【Wang Lin, Courage mixture A is adjusted to be used for experimental study Liaoning University of TCM Master's thesis that postcholecystectomy reduces choleresis, 2009- 05-01】。

The relation of biliary tract dyskinesis and choleresis：When biliary tract dyskinesis occurs, the nerve of liver and gall, body fluid Controlling mechanism balance is destroyed, and the secretion of bile and regulatory function are affected；Simultaneously because Oddi sphincter muscle obstacles, bile Discharge function be restricted, gall-bladder and courage overpressure necessarily increase, make originally for normal Amount of Bile turn into increase biliary tract An important factor for interior pressure, biliary tract dyskinesis is aggravated in turn.

In biliary tract dyskinesis, particularly postcholecystectomy, this orthofunction relation have played change.It is first Oddi sphincters reduce to the sensitiveness of the pancreozymin of Endogenous cholecystokinin one (CCK-PZ), and bile drainage power weakens, Choledochectasia and cholestasia；Oddi sphincter dysfunctions can cause repeated relapsing biliary tract pain, repeated relapsing pancreas Adenositis.Due to feed be especially satiated with food or heavy wool food after, upper abdomen or the symptom such as right Abdeminal pain, indigestion can be caused, even Oddi sphincterismus can be caused and pain occurs, especially implement cholecystectomy in the case where gallbladder function is still good Patient afterwards, it is easier to above-mentioned symptom occurs.Its pathological change is mainly choledochectasia；Emptying time extends；Binary passage presyure Rise, symptom can gently can weigh, repeatedly persistently half a year to 3 years【Wang Lin, adjust courage mixture A to be used for postcholecystectomy and reduce bile point The experimental study Liaoning University of TCM Master's thesis secreted, 2009-05-01】.

In addition, biliary tract dyskinesis after gallbladder removal, biliary system anatomical structure changes, and choledochus turns into prolonging for ductuli hepaticus communis Continuous, gallbladder function is lost, and biliary tract loses the function of compensator or trimmer pressure, because operation early postoperation choledochus is passively expanded, with weight It is new to obtain pressure balance, and replace the partial function of gall-bladder.The bile that continuous release goes out no longer is concentrated and flowed directly into through gall-bladder Duodenum.Early postoperation, because operation stimulates oddi sphincterismus, locally there is tissue hyperemia in wound, and slurries ooze out and in vain Cell is swum out of, and oedema is serious, and biliary tract path is not smooth, is flowed out, is caused to biliary tract excessive for the bile of about 800-1200ml daily Pressure, unfavorable wound healing and the foundation of regular path, be more easy to cause the serious postoperative complications such as courage leakage【Wang Lin, adjust courage Mixture A is used for experimental study Liaoning University of TCM Master's thesis that postcholecystectomy reduces choleresis, 2009-05- 01】。

Except biliary tract dyskinesis itself, some patients can also produce gastrointestinal motility disorders.If postcholecystectomy, stomach The hormones such as secretin, CCK CCK, endogenous gastrointestinal hormone YY peptides raise, and cause stomach-pylorus-duodenum cooperative motion Disorder, in addition a large amount of bile of interdigestive phase constantly enter duodenum, make patient occur duodenogastric reflux, can also produce Upper abdomen distending pain is uncomfortable, the symptom such as heartburn【Tian Fuzhou, the Clinics and Practices of Postcholecystectomy Bile road dyskinesis, China are real With surgical magazine 199,19 (6):326-327】.

Suppress clinical meaning of the choleresis to biliary tract dyskinesis：By suppressing choleresis, choleresis is reduced, Can reduce binary passage presyure power, alleviate because bile drainage power caused by oddi disturbances of sphincter weakens, choledochectasia and Cholestasia, so as to alleviate the repeated relapsing biliary tract pain caused by biliary tract dyskinesis.

Postcholecystectomy early stage, extrahepatic biliary passages are damaged, and local organization oedema is serious.By suppressing choleresis, reduce Choleresis, it is possible to reduce stimulation inflammatory reaction of the bile to impaired local organization；Alleviate caused by excessive choleresis Pressure is excessive, unfavorable wound healing and the foundation of regular path, the complication such as easy induction courage leakage etc. is postoperative.Therefore, it is postoperative effective Regulation pressure of biliary tract, control the rhythm of choleresis, improve in gall-bladder early postoperation biliary system environment for gallbladder removal Postoperative biliary tract dyskinesis rehabilitation has important clinical meaning.【Wang Lin, adjust courage mixture A to be used for postcholecystectomy and reduce courage Experimental study Liaoning University of TCM Master's thesis of juice secretion, 2009-05-01】.

Courage external form biliary tract dyskinesis PCBD, such as bile reflux gastritis【Tian Fuzhou, Postcholecystectomy Bile road power barrier The Clinics and Practices hindered, the practical surgical magazine 199,19 (6) of China:326-327】Be due to be discharged into from gall-bladder it is duodenal Bile and other intestinal juice mix, and by pylorus, countercurrently to stomach, stomach lining are stimulated, so as to caused Lymph nodes.Main disease Shape shows as abdominal fullness discomfort, and middle upper abdomen continues burn feeling, can also appear as pain after breastbone, can aggravate after the meal, with belch, Sour regurgitation, Nausea and vomiting, borborygmus, defecation be not smooth, anorexia and phenomena such as become thin【Wang Bin, Sun Tianyan, Wang Xiaoyu, Li Hong, Wu Zuoyan, bile reflux gastritis clinical research and analysis, medical research magazine the 1st phase of volume 39 in January, 2010,96-98 Page】.By suppressing choleresis, choleresis is reduced so as to reduce bile regurgitation, the stimulation to stomach lining is reduced, to bile The prevention and treatment of reflux gastritis have important clinical meaning.

Wang Lin etc. research shows, experimental model group White Rabbit is postoperative give and adjust courage mixture A after, compared with Normal group Compared with bile flow substantially lacks (P<0.01), illustrate to adjust courage mixture A to have the function that to suppress choleresis.Adjust five in courage mixture A Gall nut finds that it contains a large amount of Chinese gall boots acid, can cause the protein coagulating of gland cell and cause secretion by pharmacological research Suppress；The fruit of Cherokee rose has the function that to suppress hepatocytes secrete.Further prove to adjust courage mixture A to press down Postcholecystectomy Bile juice Secretion reason is excessive, and reduces pressure of biliary tract, improves early postoperation biliary tract oedema caused by inflammation card and operation stimulate, path is not Freely.Suppress choleresis to adjust courage mixture A to be applied to clinical treatment postcholecystectomy；Pressure of biliary tract is reduced, promotes function extensive Experimental basis is provided again.【Wang Lin, courage mixture A is adjusted to be used in experimental study Liaoning that postcholecystectomy reduces choleresis Medical pharmaceutical university Master's thesis, 2009-05-01】.

Existing medicine has domperidone, Cisapride and levosulpiride erythromycin to intend for motilin like medicine, nitre benzene Pyridine, Nitrates preparation such as isosorbide dinitrate etc., aspirin etc..The non-sterol AID such as prolonged application aspirin can be reduced Gall-bladder mucilage secretion, changes biliary lipids content so as to hinder the formation of calculus, may have one to the generation for preventing cholecystolithiasis It is set for using, but such medicine can not reverse the contractile function of the gall-bladder of asystole【Chen Shizhu, biliary system motor adjustment and work( The abnormal diagnosis and treatment of energy property biliary motility, World Chin J Digestol2003May；11(5):613-618 worlds Chinese digests Magazine ISSN1009-3079CN14-1260/R】.

Other treatment methods have surgery excision treating cholecystitis, can be with pain of alleviation【Brown,M R；Siafakas,C G； Ryan,C K；Pegoli,W；Miller, T L, Biliary Dyskinesia:A Cause of Recurrent Abdominal Pain,Diagnosis By Cck Cholescintigraphy,Relief of Pain After Cholecystectomy, Journal of Pediatric Gastroenterology＆Nutrition:October1998- Volume27-Issue4-p470, Annual Meeting of the North American Society for Pediatric Gastroenterology and Nutrition；Orlando,October22-24,1998】.But gall-bladder is cut Except art usually brings operation on biliary tract complication.Operation on biliary tract complication and biliary tract anatomical variation, disease type, at peri-operation period The factors such as reason, modus operandi and the clinical experience of patient are closely related.Cholecystectomy accounts for the 1/3 of common surgical procedures, wherein There is 5%~40% patient is postoperative abdominal pain, abdominal distension or other symptoms etc. occur, this symptom typically is referred to as into gall-bladder cuts Except postoperative syndrome (PCS).About 11%~40% patient moves without organic disease, referred to as Postcholecystectomy Bile road in PCS Power obstacle (PCBD, also known as courage inner mold PCBD).In recent years, PCBD has been to be concerned by more and more people, and this is to improving successful surgery Rate and life in patients are extremely important.And the key of cholecystectomy is postcholecystectomy early stage, extrahepatic biliary passages is damaged, Local organization oedema is serious, and excessive choleresis meeting build-up of pressure is excessive, unfavorable wound healing and the foundation of regular path, more Easily induce the postoperative complications such as courage leakage.Therefore, postoperative effective regulation pressure of biliary tract, controls the rhythm of choleresis for gall-bladder Resection aftertreatment has important clinical meaning【Wang Lin, adjust courage mixture A to be used for postcholecystectomy and reduce choleresis Experimental study Liaoning University of TCM Master's thesis, 2009-05-01】.

Existing treatment Postcholecystectomy Bile road dyskinesis method uses spasmolysis, sedative, and analgesic drug product, but There are different degrees of limitation and side effect.Treatment method includes (1) for Biliary Type PCBD, and seizure frequency is not high or degree Do not weigh, can expectant treatment, using oral or intramuscular injection spasmolysis medicine, while orally available sedative.As angina is serious, breaking-out relatively frequency and Antispasmodic is invalid, can make nasobiliary drainage and inject 0.5% lidocaine into bile duct through conduit, or underwent operative treatment.(2) it is right On the one hand it is to combine bile, to reduce reflux thing currently for the therapeutic strategy of bile reflux gastritis in courage external form PCBD Detrimental effect；On the other hand it is to improve gastroenteritic power, promotes Gastroduodenal coordination to reduce duodenogastric reflux Occur【Zhao Hongwen, the clinical analysis of 136 bile reflux gastritises, tutor；Gu Zhuying；Xu Guoqiang；Zhejiang University, clinical practice, 2007, Master's thesis】.

As described above, the method for the treatment of biliary tract dyskinesis is although more at present, but without controlling liver and gall from source The method and medicine of juice secretory volume.Due to biliary tract dyskinesis, Postcholecystectomy Bile road dyskinesis (PCBD) all with liver and gall The fluid dynamics parameter of juice such as choleresis, flow velocity, rhythm is closely related with gall-bladder and courage overpressure, if can have The suppression choleresis of effect, the infringement of stimulation and gastrointestinal mucosa of the bile to surgical wound surface is reduced, adjusts the rhythm of choleresis, Reduction pressure of biliary tract, pain of alleviation, the treatment and rehabilitation for above-mentioned disease are significant.

But although clinically there is the medicine such as urso of increase choleresis at present, and specifically for suppression courage The chemicals of juice secretion has not been reported and applied.In addition, the report of Chinese medicine and autonomic drug combined therapy biliary tract dyskinesis, Mainly using soothing liver-gallbladder as major function.Soothing liver-gallbladder function refers to pharmacologic implications for increase choleresis effect.【It is soothing the liver Postcholecystectomy Bile road 45 square Shengquans of dyskinesis are treated in cholagogic and stomach ruling by law；Zhu Shengliang；Ni Hong plum Shanghai Chinese magazines 2005-03-10】,【The research of following biliary stones operation biliary tract dyskinesis, Hou Junming, Wang Jianhua, Wang Zong are treated in soothing liver-gallbladder ruling by law Post, Jia Yong, ShanXi Chinese Medicine Academy journal, the 2nd 12-13 pages of phase of volume 31 in March, 2008】.

The representative Chinese patent drug listed has：XIAOYAN LIDAN PIAN, by 117 granted production medicine enterprise productions.Prescription (middle traditional Chinese medicines Allusion quotation version mono-, 1031-1032 pages in 2010) Herba Andrographitis, rabdosia lophanthide, quassia.Major function：Heat-clearing, clearing damp, cholagogic.For Bitter taste, costalgia caused by liver and gallbladder damp-heat；Acute cholecystitis, cholangitis, the side effect of XIAOYAN LIDAN PIAN is most to be occurred to connect for a long time Continuous to take in crowd, there is the complete atrophy of gall-bladder, function forfeiture etc. in severe patient.

In addition, energy Effective Regulation system and regulation choleresis, are suitably applied Chinese medicine and the plant for the treatment of biliary tract dyskinesis Thing medicine combines rare report.

The open source information searched shows：Composition is psoralea corylifolia, nutmeg, the fruit of Cherokee rose, Chinese gall, ginger, The tune courage mixture A of jujube composition can suppress hypercholia, and reduce pressure of biliary tract, improve early postoperation due to inflammation card and Biliary tract oedema caused by operation stimulation, promotes functional recovery, can be applied to clinical treatment Postcholecystectomy Bile road dyskinesis 【Wang Lin, courage mixture A is adjusted to be used for experimental study Liaoning University of TCM Master's thesis that postcholecystectomy reduces choleresis 2009-05-01】。

Choleresis hyperfunction (hypercholeresis, or hypercholia) is hepatic secretion after obstruction of biliary tract is alleviated Substantial amounts of thin bile, bile discharge rate maintain 1500-3000ml/ days (average 2100ml/ days), and substantial amounts of bile is lost in can Cause serious acid-base imbalance, electrolyte disturbance and liver failure.Patient death (Qin Changchun, Wu can be caused by such as dealing with improperly New people, hyperfunction six reports of choleresis, Clinical Surgery's magazine in September, 2001 the 5th phase of volume 9,338-339 pages) choleresis It is hyperfunction generally to have no clinical symptoms, but can cause serious consequence when doing bile external drainage.Author is implementing operation of liver cancer When, it is found that merging clonorchiasis cholangiectasis person easily occurs courage leakage.Bile external drainage is done to be intended to prevent bile leakage after operation, but Postoperative choleresis is hyperfunction rather common【Zheng Peiqiu, hyperfunction 21 analyses of the postoperative choleresis of clonorchiasis, the 3rd medical officer College journal, in the November, 2009 the 22nd phase of volume 31,2292-2293 pages】.

The hyperfunction treatment of choleresis has some western medical treatment methods.(1) obstruction of biliary tract is released：Generation choleresis is hyperfunction Patient, have more biliary tract retained calculus or biliary tract inflammatory it is narrow, obstruction of biliary tract should be released as early as possible, after terminating biliary extra-drainage It is hyperfunction can then choleresis to be cured.(2) bile is fed back in time, avoids the further forfeiture of bile：If courage can not be released in early days The obstruction in road, then need to feed back bile, the bile of external drainage is fed back into enteron aisle through duodenum nose conduit.(3) strengthen protect liver to control Treat：It is a type of paracholia that choleresis is hyperfunction, caused by being liver failure, therefore should strengthen liver protection treatment.【The Qin Changchun, Wu new people, hyperfunction six reports of choleresis, Clinical Surgery's magazine in September, 2001 the 5th phase of volume 9,338-339 pages】.

The post surgery treatment hyperfunction to clonorchiasis choleresis, should be with the increase of guiding amount of bile, corresponding increase Amount infused, and suitably supplement sodium acid carbonate.Drainage tube can be raised after 7d, can often reduce bile extraction.It is especially more to drainage flow Person, it must be fed back through stomach tube or encourage patient to drink bile.Vein growth hormone release inhibiting hormone (as kind peaceful) or oral atropine all can be obvious Reduce bile and secrete output.Can antihelminthic chemotherapy after stable disease, commonly use praziquantel or albendazole.Postoperative 2-4 weeks, managed through T Radiography, pressure of biliary tract and pressure flow measure, it was demonstrated that biliary tract discharges unobstructed person can tube drawing.【Zheng Peiqiu, clonorchiasis Postoperative hyperfunction 21 analyses of choleresis, Third Military Medical University's journal, in the November, 2009 the 22nd phase of volume 31,2292-2293 Page】.

The report of Chinese medicinal plant medicine treatment hypercholia is very limited, and only data of delivering is shown, lizhong decoction is used With hypercholia after iatrotechnics【Diao Benshu, Marvin's are prosperous, Zhou Jianwen, Chen Liman, hypercholia after lizhong decoction iatrotechnics 1, Journal of Traditional Chinese Medicine, 1983-09-28, page 18, total 658】.

Being currently known the information about " biliary tract dyskinesis " has：1st, application number CN201210021089, the applying date 2012.01.08, denomination of invention, the combination of minor bupleurum decoction with power and preparation method of the postoperative biliary tract dyskinesis of laparoscopic cholecystectomy are treated.2nd, application number CN200910265002, applying date 2009.12.28, denomination of invention, peppermint oil dementholized move in preparation treatment Postcholecystectomy Bile road Purposes in the medicine of power obstacle.3rd, the patent open source information in the U.S. search autonomic drug component for D-sorbitol and Homatropine methyl bromide mixture, suitable for treating biliary tract dyskinesis (Biliary Dyskinesia), inventor Halpern Alfred, denomination of invention Composition and method for treating Biliary dyskinesia publication number US2990327A).

Being currently known the information about " regulation choleresis " has：Application number CN201080008377, the applying date 2010.02.18 denomination of invention, hydrolysate of crocin.

Myrobalan Terminalia chebula Retz., terminaliae billericae,fructus Terminalia bellerica (Gaergn.) Roxb It is three kinds of autonomic drugs with emblic Phyllanthus emblica L..

Chinese Pharmacopoeia is on the books to above-mentioned three kinds of autonomic drugs.

Terminaliae billericae,fructus【Pharmacopoeia of People's Republic of China：Page 68, version in 2010, Chinese Pharmacopoeia Commission compiles, Beijing：China Medical Science Press .2010.1, ISBN978-7-5067-4439-3】.Function and cure mainly for：It is clearing heat and detoxicating, blood-nourishing is restrained, Coordinating the drug actions of a prescription.For various heat symptom-complexs, rush down dysentery, grasserie, liver and bladder disease, eak after being ill.

Emblic【Pharmacopoeia of People's Republic of China：Page 167, version in 2010, Chinese Pharmacopoeia Commission compiles, Beijing：China Medical Science Press .2010.1, ISBN978-7-5067-4439-3】.Function is with curing mainly：Clearing heat and cooling blood, food digesting stomach fortifying are raw Tianjin cough-relieving.For blood-head blood stasis, indigestion, abdominal distension, cough, laryngalgia, dry.

Myrobalan【Pharmacopoeia of People's Republic of China：Page 173, version in 2010, Chinese Pharmacopoeia Commission compiles, Beijing：Middle traditional Chinese medical science Medicine Science Press .2010.1, ISBN978-7-5067-4439-3】.Function is with curing mainly：Relieving diarrhea with astringents, astringe the lung to stop cough, fall fire Relieving sore-throat.For protracted dysentery and diarrhea, prolapse of the anus of having blood in stool, the deficiency syndrome of the lung is breathed with cough, and is coughed long more than, pharyngalgia sound is mute.

Proved recipe the most famous contains one or more of components of above-mentioned three kinds of autonomic drugs more in Tibetan medicine.Such as, record China is entered The prescription 25-component Song-shi capsules of people's republic's pharmacopeia version page 408 in 2010, prescription are turquoise 50g pearl 10g coral Zhu 40g Sand 20g myrobalan (stoning) 50g iron filings (myrobalan's system) 100g emblic 50g Oletum Trogopterori paste 40g santal 40g dalbergia wood 40g banksia rose horse pockets Bell 50g malabar nut 50g cow-bezoar 5g costus root 60g pseudo-ginseng 50g scaphoidhelmet monkshood herb 40g nutmeg 20g cloves 25g pectinate rockfoils 50g terminaliae billericae,fructuses (stoning) 5g Tabasheer 35g west safflower 5g common bombax flower 35g Moschus 0.25g calcareous tufas 35g.Its function and cure mainly for： It is clearing heat and detoxicating, soothing liver-gallbladder, stagnation resolvation.For stagnation of QI due to depression of the liver, blood stasis, hepatotoxicity, hepatodynia, hepatic sclerosis, liver infiltration and various anxious, slow Property hepatitis and cholecystitis.The soothing liver-gallbladder function of being mentioned in this side refers to pharmacologic implications for increase choleresis effect, with text It is similar to offer the pharmacological action of report, as China National medicine will is recorded：40~100ml/kg of water extract of terminaliae billericae,fructus pericarp and When 90% 10~40mg/kg of ethanol extract injects to dog, several no influences of secretion of the water extract on bile；And alcohol extracting thing It can increase dog choleresis, total solids content has obvious increase in bile【China National medicine will, volume Two, Chinese medicine Biological products assay institute, Yunnan provincial institute for drug control are write, and People's Health Publisher publishes, Xinhua Bookstore's Beijing sale room hair OK, April nineteen ninety the 1st edition).The suppression choleresis medicine that the choleresis increase pharmacological action recorded herein is combined with the present invention Reason acts on contrast.

The document of other one or more of components for containing above-mentioned three kinds of autonomic drugs also has：

The prescription Tibetan medicine for entering to record Pharmacopoeia of People's Republic of China has Ershiwuwei zhenzhu wan【Pharmacopoeia of People's Republic of China One page -408 of version in 2010】, component is：Pearl, nutmeg, calcareous tufa, tsaoko, cloves, dalbergia wood, cardamom, myrobalan, santal, Emblic, agalloch eaglewood, Chinese cassia tree, terminaliae billericae,fructus, crab, the banksia rose, Fructus Malvae Vertillatae, the Bi roots of grass, Strawberry Seedlings, Lapis Micae Aureus, cornu bubali (system), Cuminum celery Son, west safflower, fennelflower seed, In vitro cultured Calculus Bovis, muscone.Its function is had one's ideas straightened out with curing mainly to calm the nerves.For apoplexy；Half body It is unsuccessful, facial paralysis, remain unconscious, conciousness disorder, delirious speech is gone mad.

25-component coral ball【Pharmacopoeia of People's Republic of China one page -409 of version in 2010】, component is：Coral 75g is precious Pearl 15g lapis lazuli 20g mother-of-pearl 50g myrobalan's 100g costus root 60g safflower 80g cloves 35g agalloch eaglewood 70g cinnabar 30g keel 40g stoves Sweet stone 25g encephaloliths 25g magnetites 25g limoniterras 25g sesames 40g cucurbit 30g Flos Radix Asteris 45g Swertia patens 80g Rhizoma Acori Calami 50g radix aconiti agrestis 45g DAJIANJU 75g radix glycyrrhizae 75g west safflower 25g Moschus 2g.Function and cure mainly for：Have one's ideas straightened out, dredging collateral, analgesic.For " white vein ", Obnubilation, body is numb, and Light-headedness, brain pain, blood pressure is uncomfortable, headache, epilepsy and various godhead pain.

Ten five tastes agalloch eaglewood balls【Pharmacopoeia of People's Republic of China one page -417 of version in 2010】.Medicine forms：Agalloch eaglewood 100g Tibet inula root 150g santal 50g santal 150g safflower 100g nutmeg 25g high mountain horseradish dish 150g Caulis Rubi corchorifoliis (peeling, the heart) Few (peeling) 100g asarums 50g calcareous tufas 100g fructus choerospondiatis 50g myrobalan (stoning) 150g terminaliae billericae,fructuses (stoning) the 80g emblics of 200g wood rattans Sub- 100g.Major function：The regulation of qi and blood, cough-relieving, calm the nerves.For qi and blood stasis, pectoralgia, dry cough shortness of breath, insomnia.

Wei Zhen Zhu Wan【Pharmacopoeia of People's Republic of China one page -423 of version in 2010】.Medicine composition pearl, santal, 70 tastes such as dalbergia wood, radix glycyrrhizae, Tabasheer, west safflower, In vitro cultured Calculus Bovis, muscone, coral, agate, nine eyestones, seat platform.Its Major function is calm to calm the nerves, clearing and activating the channels and collaterals, the regulation of qi and blood, consciousness regaining.It is uncomfortable for " black white vein ", " dragon's blood "；In Wind, paralysis, hemiplegia, epilepsy, cerebral hemorrhage, cerebral concussion, heart disease, hypertension and neurological disorders.

Ten can disappear ball simply【Pharmacopoeia of People's Republic of China one page -415 of version in 2010】.Major function is stagnation resolvation row Blood, stimulate the menstrual flow and hasten parturition.For Amenorrhea, irregular menstruation, difficult labour, mazischesis, postpartum blood stasis stomachache.

Bawei Chenxiang dissipates【Pharmacopoeia of People's Republic of China one page -415 of version in 2010】.Major function is to control the heat that clears away heart-fire, Nourishing heart, calm the nerves, have one's ideas straightened out.Make a psychological attack for pyreticosis, coma and delirium, coronary heart disease, angina pectoris.

Wuweishexiang Pill【Pharmacopoeia of People's Republic of China one page -536 of version in 2010】.Major function is anti-inflammatory, analgesic, Wind-dispelling.For tonsillitis, angina, influenza, anthracnose, rheumatic arthritis, neuralgia, have a stomachache, toothache.

Tibetan medicine Renqingmangjue【Pharmacopoeia of People's Republic of China one page -572 of version in 2010】.Major function is clearing heat and detoxicating, benefit Liver and nourishing stomach, more sore improving eyesight inducing resuscitation, nourishing and fit keeping function.For poison naturally, prepare the various nosotoxicosis such as poison；" Baconic's wood cloth ", alimentary canal Ulcer, acute/chronic gastroenteritis, atrophic gastritis, ascites, leprosy etc..

RP-HPLC【Pharmacopoeia of People's Republic of China one page -573 of version in 2010】.Clearing heat and detoxicating, mediation nourishing.For " imperial, red bar, Baconic " each disease, old gastroenteritis, ulcer, " wooden cloth " disease, atrophic gastritis, various nosotoxicosis；Syphilis, fiber crops Wind, outmoded pyreticosis, anthrax, furuncle pain, dry yellow water, suppurate etc..

Liuwei Anxiao dissipates【Pharmacopoeia of People's Republic of China one page -602 of version in 2010】.Major function be and stomach invigorating the spleen, Consumer product dredge stasis, promoting blood circulation and stopping pain.For the stomachache turgor caused by incoordination between the spleen and the stomach, internal stagnation, indigestion, constipation, dysmenorrhoea.

JIEBAI WAN【Pharmacopoeia of People's Republic of China one page -955 of version in 2010】.Major function is strengthening the spleen and stomach, analgesic Antiemetic, separating clear and excreting turbid.For fullness and oppression of chest and abdomen, gastral cavity pain, indigestion, inverse diarrhea of vomitting, difficult urination.

Urge soup ball【Pharmacopoeia of People's Republic of China one page -1187 of version in 2010】.Major function is relieving superficies by cooling, cough-relieving Analgesic.For having some inkling of a cold, cough headache, joint pain；Prevent and treat influenza.

18 taste cuckoo balls【Nineteen ninety-five version《Drug Standard of Ministry of Public Health of the Peoples Republic of China》(Tibetan medicine) first.WS3— BC—0180—95】Component is：Rhododendron anthopogonoide, tsaoko, myrobalan's (stoning), santal, terminaliae billericae,fructus, dalbergia wood, emblic, caudate sweetleaf leaf, Calcareous tufa, ZANGQIANCAO, safflower, shellac, nutmeg, Radix Gentianae Macrophyllae flower, cloves, licorice root ointment, cardamom, agalloch eaglewood.Major function is：Wind-dispelling Dredging collateral, promoting blood circulation.For numb limb caused by " white vein ", tremble, muscular atrophy, tendon contraction, the disease such as facial paralysis.

Chinese Tibetan medicine【The first volume, Qinghai provincial institute for drug control, Qinghai Tibet Medical Institute compile, and Shanghai science and technology goes out Version society publishes, distribution, October the 1st edition, page 51 to 53 in 1996】.Form and be：Emblic 75g madder 60g Adhatoda Vacica Nees 50g is purple Even the 50g bases of a fruit reach 40g slags to careless 50g banksia rose birthwort 30g stems of noble dendrobium 40g Herba Dracocephali Tanguticis 50g radix onosmatis 75g coriander 40g Rhizoma Rhodiolae kirilowiis 30g floods Tame and docile cream 35g terminaliae billericae,fructus 50g myrobalan's 75g dalbergia wood 100g cow-bezoar 1g safflower 65g hooker winghead root 40g pseudo-ginseng 40g Semen Herpetospermis 40g and hide wood The fragrant wide muscle rattan 75g Fructus Hippophae extractums 50g of 50g polyadenous XUANGOUMU 25g.It is finely ground altogether above in addition to cow-bezoar, it is mixed into cow-bezoar and mixes thoroughly.Energy cool blood, Blood is held back, is depressured.Zhiduo County's mass formed by blood stasis, high blood pressure, liver and gall pain, celostomia hot eyes, lip is blue, irregular menstruation.

18 taste myrobalan's balls, authentication code：Chinese medicines quasi-word Z20023246, manufacturing enterprise：Draw bent refreshing water Tibetan medicine in male bar of Tibet Factory, composition：Myrobalan, safflower, cardamom, slag tame and docile cream, Swertia patens, sword bean, caudate sweetleaf leaf, shellac, ZANGQIANCAO, Chinese juniper, mango core, Pu Peach, bonduc, Lapis Micae Aureus, crab, eastern certain herbaceous plants with big flowers fruit, iron staff Chui, muscone.Indication：Clear kidney heat, anti-inflammatory.For urethra Infection, blood urine, lumbar sprain, pain in the back caused by nephrosis, hip pain, thigh shouting pain, instep edema.

18 taste myrobalan's diuresis balls, authentication code：Chinese medicines quasi-word Z20043806, manufacturing enterprise：Tibet Autonomous Region pharmaceutical factory, Composition：Myrobalan, safflower, cardamom, emblic, turmeric, barberry skin, puncture vine, Lapis Micae Aureus, Chinese juniper, sword bean, bear gall, calculus bovis factitius etc. 18 tastes.Major function：Supplementing the kidney to control the nocturnal, diuresis.For nephrosis, waist kidney pain, frequent micturition, turbid urine, diabetes, seminal emission.

30 five tastes agalloch eaglewood balls, authentication code：Chinese medicines quasi-word Z20023269, production unit：Tibet Changdu Tibetan Pharmaceutical Factory, it is main Want composition：Agalloch eaglewood, cinnamomum camphora, white agalloch eaglewood, santal, dalbergia wood, Tabasheer, safflower, cloves, nutmeg, cardamom, tsaoko, myrobalan (go Core), terminaliae billericae,fructus (stoning), emblic (stoning), the banksia rose, fructus choerospondiatis, Tibet inula root, XUANGOUMU, wide muscle rattan, kaempferia galamga, common bombax flower, Strychnos nux-vomica Son, frankincense, styrax, BAXIAGA, Saxifraga umbellulata Hook.f.et Thoms, Lagotis glauca, spiny meconopsis herb, DAJIANJU, Low Cremanthodiun, from clothes, pomegranate Son, Aconitum Szechenyianum Gay, heart of Bos gaurus, muscone.Major function：Clear pest heat, wind-dispelling, beneficial lung, sharp numbness.Quoted copiously from many sources for pestilence, heat, grand phase Disease, pyreticosis initial stage, lung chronic illness, lung iron cloth disease, cough with dyspnea, rheumatism, the grand disease of the heart.And the fullness sensation in chest back of the body caused by stopping up on qi and blood Bitterly, pant, dry cough.

Ten tsaoko balls simply, authentication code：Chinese medicines quasi-word Z20023204, production unit：Tibet hanuman medicine company Limited Liability Company, composition：Tsaoko 70g shellac 100g ZANGQIANCAO 100g myrobalan's 180g Chinese ephedra 10g banksia rose 120g cloves 30g cardamoms 50g hides Banksia rose 100g Semen Herpetospermi 30g Bi roots of grass 50g.Function is with curing mainly：Invigorating the spleen.For abdominal distension, borborygmus caused by fever and chills spleen disease, spleen area pain Bitterly, tongue and cyanotic lips, indigestion, fart are frequent.

As can be seen here, either document records the medicine that has still produced, one kind containing above-mentioned three kinds of autonomic drugs or The formula of several components, do not show with the pharmacological actions such as choleresis are suppressed, suitable for treating choleresis, discharge, adjust Save the related biliary tract dyskinesis (Biliary dyskinesia) of dysfunction, including Postcholecystectomy Bile road dyskinesis And bile reflux gastritis (PCBD).

The content of the invention

The present invention discloses a kind of pharmaceutical composition for treating courage relevant disease, preparation method according to the deficiencies in the prior art And application thereof.It is an object of the invention to provide a kind of autonomic drug combination and preparation method thereof, said composition, which has, suppresses bile point The effect of secreting etc., suitable for treating choleresis, discharge, the disorderly related biliary tract dyskinesis (Biliary of regulatory function Dyskinesia), the medicine of relevant disease is treated for preparing.

The present invention is achieved through the following technical solutions：

Treat the pharmaceutical composition of courage relevant disease, it is characterised in that composition is made up of the medicine of following portions by weight： Emblic 10-0.5 parts；Myrobalan's 7-0.1 parts；Terminaliae billericae,fructus 8.5-0.1 parts.

The composition is preferably made up of the medicine of following portions by weight：Emblic 4.0-2.0 parts, myrobalan's 3.2-0.5 parts, Terminaliae billericae,fructus 2.8-0.4 parts.

A kind of preparation method for the pharmaceutical composition for treating courage relevant disease,

It is characterized in that comprise the following steps：

(1) weigh each raw material by the proportion of composing of claim 1 or 2 to mix, add 6-20 times to measure decocting and boil 2 times, every time 1 Hour, filtration, merging filtrate, put in vacuum concentration pot, 60 DEG C, relative density is under the conditions of 0.02mpa is concentrated under reduced pressure into 20 DEG C 1.10-1.25 extract solution；

(2) step (1) extract solution can be prepared into oral liquid or capsule.

It is prepared by oral liquid：Step (1) extract solution adds agar, honey to mix in right amount, and 4 DEG C are placed 48 hours, and filtration, filtrate adds Appropriate flavor enhancement, mixing, gabon profit soil is appropriate, mixes, and 4 DEG C are placed 48 hours, are filtered repeatedly, and filtrate is filling, are sterilized, and are examined, Packaging, storage, is made oral liquid；

It is prepared by capsule：Step (1) extract solution adds absolute ethyl alcohol to ethanol content and reaches 70%, fully mixes, stood At night, filtration, after filtrate recycling ethanol, put in vacuum concentration pot, 60 DEG C, 0.02mpa it is relatively close under the conditions of being concentrated under reduced pressure into 20 DEG C Spend the thick paste for 1.28-1.40；By mass fraction 7:1:1 to take starch, dextrin, Icing Sugar be auxiliary material, and thick paste mixing granulation, 60 DEG C Dry, purify below, crush, sieving is filling that capsule is made.

The purposes of the pharmaceutical composition of above-mentioned treatment courage relevant disease, pharmaceutical composition, which is used to prepare, suppresses choleresis mistake Application in drug.

The purposes of the pharmaceutical composition of above-mentioned treatment courage relevant disease, pharmaceutical composition are used to prepare treatment biliary tract power barrier Hinder the application in medicine.

Pharmaceutical composition described further is used to prepare the application in pain medication caused by treatment biliary tract dyskinesis.

Pharmaceutical composition described further is used to prepare in upper right abdominal pressure pain medicine caused by treatment biliary tract dyskinesis Using.

Pharmaceutical composition described further is used to prepare biliary tract, Oddi sphincter functions caused by treatment biliary tract dyskinesis Application in disorderly medicine.

Pharmaceutical composition described further is used to prepare bile reflux gastritis medicine caused by treatment biliary tract dyskinesis In application.

The purposes of the pharmaceutical composition of above-mentioned treatment courage relevant disease, pharmaceutical composition are used to prepare treatment courage external form biliary tract Application in dyskinesis medicine.

Formulation workable for drug regimen and its extract of the present invention has oral liquid, particle, syrup, capsule, tablet.

Above-mentioned three tastes autonomic drug fruit is pressed portfolio ratio formula by the present invention, is handled through stoning, with water, ethanol and other fit The solvent extraction effective extract of conjunction；It is filtered, the technique such as removal of impurities；Through being concentrated under reduced pressure, proper auxiliary materials are added, is made and is available for clinic The oral liquid of clothes for patients, capsule and other oral formulations.The quality standard of preparation meets the standard of product, repeatability, The inherent qualities such as controllability requirement, to ensure the reliability of its pharmacological evaluation and clinical efficacy and repeatability.On this basis Carry out pharmacological evaluation, safety experiment and clinical trial, it was demonstrated that its advantage and purposes.

Beneficial effect and purposes：Pharmaceutical composition of the present invention is shown in zoopery significantly suppresses normal choleresis Effect, and can the abnormal hypercholia of conspicuousness suppression；Biliary tract internal dynamics parameter can be changed, reduce gall-bladder and bile duct internal pressure Power, the resistance of Oddi sphincters is reduced, reduce the infringement of stimulation and gastrointestinal mucosa of the bile to the biliary system incision surface of a wound, reach alleviation Pain, promote the effect of functional recovery, suitable for biliary tract dyskinesis, including Postcholecystectomy Bile road dyskinesis and courage outside The treatment of type biliary tract dyskinesis such as bile reflux gastritis.60 are diagnosed as with the clinical trial table of biliary tract dyskinesis case Bright, present invention combination can significantly alleviate following symptom：The right Upper abdominal pain of recurrent exerbation, upper right abdominal pressure pain, upper abdomen are persistently burnt Sense, pain after breastbone, and other simultaneous phenomenons (belch, sour regurgitation, Nausea and vomiting, anorexia and become thin).Acute toxicity testing Show more than 300 times of the maximum administration dosis tolerata behaviour dosage of present invention combination oral liquid.Belong to non-toxic type level of security.For a long time Toxicity test has no the Pathomorphology damage phenomenon of important organ, shows that long-term takes what present invention combination oral liquid used Security.

Brief description of the drawings

Fig. 1 is influence of the present invention combination to normal choleresis rate of change；

Fig. 2 is influence of the present invention combination to abnormal choleresis rate of change caused by single-dose；

Fig. 3 is antagonism of the present invention combination to abnormal choleresis caused by multiple dosing；

Fig. 4 is influence of the present invention combination to abnormal choleresis rate of change caused by multiple dosing.

Embodiment

Embodiment 1

The preparation method step of oral liquid of the present invention is as follows：

Take emblic 4.0-2.0 parts by weight, myrobalan's 3.2-0.5 parts by weight, terminaliae billericae,fructus 2.8-0.4 parts by weight, through cleaning, nothing Impurity, free from insect pests, nothing is gone mouldy, standby after the assay was approved.

Above-mentioned each component is mixed, adds 6-20 times of weight water to decoct 2 times, 1 hour every time, filtration, merging filtrate, puts vacuum In concentration tank, 60 DEG C, 0.02mpa be concentrated under reduced pressure into relative density be 1.10-1.25 (20 DEG C) extract solution, add agar, honey Appropriate to mix, 4 DEG C are placed 48 hours, and filtration, filtrate adds appropriate flavor enhancement, are mixed, and gabon profit soil is appropriate, mixes, and 4 DEG C are placed 48 Hour, filter repeatedly, the filtrate feeding automatic bottling department of 100,000 cleaning grades is filling, 30 milliliters every bottle, sterilizes, and examines, and packaging, enters Storehouse, present invention combination oral liquid (SLJ oral liquids) is made.

Oral liquid of the present invention need to reach following quality standard：

【Character】This product is liquid of the yellowish-brown to brown；It is sweet, it is slightly sour, it is slightly puckery.

【Differentiate】(1) this product 30ml is taken, puts and about 10ml is concentrated into water-bath, let cool, adds ethanol 30ml, fully stirs evenly, it is quiet Put 2 hours, filter, filtrate steams to about 5ml, add water 10ml, stir evenly, and with extracted by ether 2 times, each 20ml, merges ether solution, steams Dry, residue adds methanol 1ml to make dissolving, as need testing solution.Myrobalan control medicinal material 1g separately is taken, adds water 50ml to boil, is kept micro- Boiling 30 minutes, filtration, filtrate, which is put, is concentrated into 20ml in water-bath, is extracted 2 times, each 15ml with ethyl acetate, merges extract solution, steams Dry, residue adds methanol 1ml to make dissolving, as control medicinal material solution.According to thin-layered chromatography (Chinese Pharmacopoeia one annex of version in 2010 VIB) test, draw the above-mentioned μ l of need testing solution 10, the μ l of control medicinal material solution 5, put respectively on same silica gel g thin-layer plate, with Toluene-chloroform-methanol (5：10：3) it is solvent, deploys, take out, dry, spray with 10% ethanol solution of sulfuric acid, in 105 DEG C of baking It is clear to spot development.In test sample chromatogram, on position corresponding with control medicinal material chromatogram, show one blue spot of identical Point.

(2) this product 30ml is taken, puts and about 10ml is concentrated into water-bath, let cool, adds ethanol 30ml, stirs evenly, stands 2 hours, filter Cross, filtrate is steamed to about 5ml, is added water 10ml, is stirred evenly, and by polyamide column (30~60 mesh, 5g, internal diameter 1.5cm, dry method), is collected Efflux, eluted with water 50ml, collect eluent and merge with efflux, put water-bath and be concentrated into 20ml, 2 are extracted with ethyl acetate It is secondary, each 20ml, merge extract solution, add water 20ml, shake up, place layering, take upper liquid to be evaporated, it is molten that residue adds methanol 1ml to make Solution, as need testing solution.Terminaliae billericae,fructus control medicinal material 1g separately is taken, adds water 50ml to boil, keeps micro-boiling 30 minutes, filtration, filtrate Put and 20ml is concentrated into water-bath, extracted 2 times, each 15ml with ethyl acetate, merge extract solution, be evaporated, residue adds methanol 1ml Make dissolving, as control medicinal material solution.Tested according to thin-layered chromatography (one annex VIB of Chinese Pharmacopoeia version in 2010), in absorption Each 10 μ l of two kinds of solution are stated, are put respectively on same silica gel g thin-layer plate, with toluene-chlorofonn-ethylacetate-methanol (8：5：3：2) For solvent, deploy, take out, dry, spray with 20% alchlor ethanol solution, hot blast drying, put under ultraviolet lamp (365nm) Inspect.In test sample chromatogram, on position corresponding with control medicinal material chromatogram, show the fluorescence spot of a same color.

(3) emblic control medicinal material 1g is taken, adds water 50ml to boil, keeps micro-boiling 30 minutes, filtration, filtrate is put dense in water-bath 20ml is reduced to, is extracted 2 times, each 15ml with ethyl acetate, merges extract solution, is evaporated, residue adds methanol 1ml to make dissolving, as Control medicinal material solution.Tested according to thin-layered chromatography (5 one annex VIB of Chinese Pharmacopoeia version in 2010), draw and differentiate under (2) item Need testing solution and each 5 μ l of above-mentioned control medicinal material solution, put prepared in same with 0.2mol/l potassium dihydrogen phosphates respectively On silica gel g thin-layer plate, with chlorofonn-ethylacetate-methyl alcohol-formic acid (9：9：3：0.2) it is solvent, deploys, take out, dry, sprays With 10% ethanol solution of sulfuric acid, heated about 5~7 minutes at 105 DEG C, put and inspected under ultraviolet lamp (365nm).Test sample chromatogram In, on position corresponding with control medicinal material chromatogram, show an identical yellow-green fluorescence spot.

【Check】Relevant every regulation (one annex IJ of Chinese Pharmacopoeia version in 2010) under mixture item should be met.

【Assay】According to high performance liquid chromatography (one annex VID of Chinese Pharmacopoeia version in 2010) measure this product sign Component content, to control the quality of combination product of the present invention.

(1) corilagin (Corilagin) assay

Chromatographic condition and system suitability, it is filler with octadecylsilane chemically bonded silica；The vinegar of acetonitrile -0.5% Acid solution (1:9) it is mobile phase；Detection wavelength is 272nm.Number of theoretical plate is calculated by corilagin peak should be not less than 2000.

The preparation of reference substance solution：It is appropriate that precision weighs corilagin reference substance, add 50% methanol be made every 1ml containing about 50ug solution, is produced.

The preparation of need testing solution：Precision measures this product 5ml, put D101 types large pore resin absorption column (20 × 150mm of Ф, Resin loading amount：On 10g), eluted with water 20ml, discard aqueous, then eluted with 70% ethanol 80ml, collected eluent, put 100ml In measuring bottle, scale is added water to, is shaken up, is produced.

Determination method：Accurate absorption reference substance solution and each 10ul of need testing solution respectively, injection liquid chromatograph, measure, Calculate content.This product every must not be less than 25mg containing corilagin (C27H22O18).

(2) gallic acid (gallic acid) assay

Chromatographic condition and system suitability, it is filler with octadecylsilane chemically bonded silica；The phosphorus of methanol -0.1% Acid solution (1:19) it is mobile phase；Detection wavelength is 215nm.Number of theoretical plate is calculated by gallic acid peak should be not less than 2000.

The preparation of reference substance solution：It is appropriate that precision weighs gallic acid reference substance, adds 50% methanol that every 1ml is made containing about 25 μ g solution, is produced.

The preparation of need testing solution：Precision measures this product 1ml, puts in 250ml measuring bottles, adds 50% methanol to shake up to scale, Filtration, as need testing solution.

Determination method：Accurate absorption reference substance solution and each 10 μ l of need testing solution respectively, injection liquid chromatograph, measure, Calculate content.This product must not be less than 4.5mg per 1ml (gallic acid C7H6O5) containing gallic acid.

【Usage and dosage】Orally, one time 1 (30mL), 1-2 times on the one.

Embodiment 2

The step of preparation technology of capsule of the present invention, is as follows：

Take emblic 4.0-2.0 parts by weight, myrobalan's 3.2-0.5 parts by weight, terminaliae billericae,fructus 2.8-0.4 parts by weight, through cleaning, nothing Impurity, free from insect pests, nothing is gone mouldy, standby after the assay was approved.

Above-mentioned each component is mixed, adds 6-20 times to measure decocting and boils 2 times, 1 hour every time, filtration, merging filtrate, it is dense to put vacuum In contracting tank, 60 DEG C, 0.02mpa be concentrated under reduced pressure into the extract solution that relative density is 1.10-1.25 (20 DEG C), add ethanol to ethanol Content reaches 70%, fully mixes, stands overnight, and filters, and after filtrate recycling ethanol, puts in vacuum concentration pot, 60 DEG C, 0.02mpa is concentrated under reduced pressure into the thick paste that relative density is 1.28-1.40 (20 DEG C).Take starch, dextrin, Icing Sugar (7:1:1) supplemented by Material, with thick paste mixing granulation, less than 60 DEG C dryings, 100,000 grades of cleaning shops are sent into, crushed, sieving, by every 0.3g specification, used The filling capsule of fully-automatic capsule loader, examine, pack, storage, be stored at shady and cool dry.

Capsule of the present invention reaches following quality standard：

【Character】This product is capsule, and content is particle of the yellowish-brown to brown；It is sweet, it is slightly sour, puckery.

【Differentiate】(1) this product content 2.7g is taken, finely ground, heating water 20ml is stirred to dissolve, and is centrifuged, is taken supernatant, add Ethanol 30ml, is fully stirred evenly, and stands 2 hours, and filtration, filtrate steams to about 5ml, add water 10ml, stir evenly, with extracted by ether 2 times, often Secondary 20ml, merge ether solution, be evaporated, residue adds methanol 1ml to make dissolving, as need testing solution.Myrobalan control medicinal material 1g separately is taken, Add water 50ml to boil, keep micro-boiling 30 minutes, filtration, filtrate, which is put, is concentrated into 20ml in water-bath, extracts 2 times with ethyl acetate, often Secondary 15ml, merge extract solution, be evaporated, residue adds methanol 1ml to make dissolving, as control medicinal material solution.According to thin-layered chromatography (China One B of annex VI of pharmacopeia version in 2010) experiment, each 10ul of above two solution is drawn, is put respectively in same silica gel g thin-layer plate On, with toluene-chloroform-methanol (5:10:3) it is solvent, deploys, takes out, dry, spray with 10% ethanol solution of sulfuric acid, 105 It is clear DEG C to be heated to spot development.In test sample chromatogram, on position corresponding with control medicinal material chromatogram, show one indigo plant of identical Color spot point.

(2) this product content 2.7g is taken, finely ground, heating water 20ml is stirred to dissolve, and is centrifuged, is taken supernatant, add ethanol 30ml, fully stir evenly, stand 2 hours, filtration, filtrate is steamed to about 5ml, adds water 10ml, stir evenly, and passes through polyamide column (30~60 Mesh, 5g, internal diameter 1.5cm, dry method), add water 50ml to elute, collect eluent, put water-bath and be concentrated into 20ml, extracted with ethyl acetate 2 times, each 20ml, merge ethyl acetate liquid, add water 20ml, shake up, place layering, divide and take upper liquid to be evaporated, residue adds methanol 1ml makes dissolving, as need testing solution.Terminaliae billericae,fructus control medicinal material 1g separately is taken, adds water 50ml to boil, keeps micro-boiling 30 minutes, filter Cross, filtrate, which is put, is concentrated into 20ml in water-bath, extracted 2 times, each 15ml with ethyl acetate, merges extract solution, is evaporated, residue adds first Alcohol 1ml makes dissolving, as control medicinal material solution.Test, inhale according to thin-layered chromatography (one B of annex VI of Chinese Pharmacopoeia version in 2010) Each 10ul of above-mentioned two kinds of solution is taken, is put respectively on same silica gel g thin-layer plate, with toluene-chloroform-ethyl acetate-methanol (8:5: 3:2) it is solvent, deploys, takes out, dry, put and inspected under ultraviolet lamp (365nm).In test sample chromatogram, with control medicinal material On the corresponding position of chromatogram, show the fluorescence spot of a same color.

(3) emblic control medicinal material 1g is taken, adds water 50ml to boil, keeps micro-boiling 30 minutes, filtration, filtrate is put dense in water-bath 20ml is reduced to, is extracted 2 times, each 15ml with ethyl acetate, merges extract solution, is evaporated, residue adds methanol 0.5ml to make dissolving, makees For control medicinal material solution.Test, draw according to thin-layered chromatography (one 5B of annex VI of Chinese Pharmacopoeia version in 2010)【Differentiate】(2) item Under need testing solution and each 15ul of control medicinal material solution, put prepared in same with 0.2mol/L potassium dihydrogen phosphates respectively On silica gel g thin-layer plate, with chloroform-ethyl acetate-methyl alcohol-formic acid (9:9:3:0.2) it is solvent, deploys, take out, dry, sprays With 10% ethanol solution of sulfuric acid, heated about 5 minutes at 105 DEG C, put and inspected under ultraviolet lamp (365nm).In test sample chromatogram, On position corresponding with control medicinal material chromatogram, show an identical yellow-green fluorescence spot.

【Check】Relevant every regulation (one annex IL of Chinese Pharmacopoeia version in 2010) under capsule item should be met.

【Assay】Determined according to high performance liquid chromatography (one D of annex VI of Chinese Pharmacopoeia version in 2010).Chromatographic condition Filler is used as by the use of octadecylsilane chemically bonded silica with system suitability；The phosphoric acid solution of methanol -0.1% (1:19) it is stream Dynamic phase；Detection wavelength is 215nm.Number of theoretical plate is calculated by gallic acid peak should be not less than 2000.

It is appropriate that the preparation precision of reference substance solution weighs gallic acid reference substance, add 50% methanol be made every 1ml containing about 25ug solution, is produced.

The preparation of need testing solution takes the content under this Pin Installed amount differences, finely ground, takes about 0.1g, accurately weighed, puts In 100ml measuring bottles, add 50% methanol solution 50ml, be ultrasonically treated 15 minutes, take out, put to room temperature, add 50% methanol to scale, Shake up, filter, take subsequent filtrate, produce.

Determination method difference is accurate to draw reference substance solution and each 10ul of need testing solution, injects liquid chromatograph, determines, Produce.

This product every must not be less than 10mg containing gallic acid (C7H6O5).

【Usage and dosage】Orally, one time 3,3 times a day.

Embodiment 3, present invention combination pharmacologic effectiveness research

Influence of the present invention combination of experiment 1. to normal choleresis：

Cavy is grouped at random by body weight, every group 10.Fasting can't help water 12 hours before experiment, and each group animal is black with 20% Make ductus choledochus insertion silicone tube operation after carrying out sugared 1mL/100g.bw intraperitoneal injection of anesthesia.Collected after the completion of operation, measure bile body Accumulate to observe the stability of choleresis.Tested material is using clinical plan dosage as Main Basiss.Globefish is converted into according to body surface area The dose,equivalent of mouse is 1.17g crude drugs/kg, takes 0.52g crude drugs/mL SLJ oral liquids, i.e. 5.2g is administered by 1mL/100g Crude drug/kg.After choleresis is steady (90 minutes), by table 1-1 settings, duodenum gives tested material respectively.

Influence experiment packet and dosage of the table 1-1 present invention combinations to normal choleresis

* because present invention combination oral liquid pH value is 3.00.Therefore it is 2.82 citric acid solutions (10mg/mL) from pH value Compareed for acid medium, to exclude influence of the acid medium to choleresis.

Every group since being given tested material, was collected every 30 minutes and accurately measures bile volume, calculated by following equation Choleresis rate of change.

Choleresis rate of change (%)=100 (B-A)/A

A：Preceding 30 minutes choleresis；B：30 minutes choleresis afterwards.Period choleresis after negative value represents The choleresis at more previous time point reduces.Increase on the occasion of representing.

It is poor different in nature (Spss softwares, Nonparametric Analysis) to collect the processing that takes statistics of each experimental group data

As a result (being shown in Table 1-2, Fig. 1) is shown, after model control group gives choleretic urso, bile point The amount of secreting added 44.3% (P in 30 minutes<0.01), cause bile abnormal secretion, illustrate this experimental animal system to by It is normal to try thing reaction, can apply.Hereafter, model control group secretory volume gradually reduces on the basis of increasing, and shows that bear deoxygenates The choleresis facilitation duration of cholic acid is shorter.And comparing the time identical, negative control group choleresis is all the time Keep gentle by 2.8-5.4% speed to reduce.With urso on the contrary, the present invention is combined and had no in 30 minutes to animal Normal choleresis has an obvious effect, but upon administration 30-90 minutes show the extremely significant effect for reducing choleresis, Choleresis reduces 26.6% and 17.2% (P respectively<0.01), still maintained afterwards higher than negative control group after 90 minutes Rate of change.Citric acid group relatively has no difference with negative control group, illustrates that acid medium can not be to courage in tested any time period Juice secretion impacts, it was demonstrated that present invention combination reduces the effect of choleresis, is not that the acidity of the oral liquid causes.

Influence (%) (x ± sd) of the table 1-2 present invention combinations to normal choleresis rate of change

Note："-" represents the choleresis drop at the latter period, the choleresis time point more previous time point It is low.Compared with negative control group, * represents P<0.05；* represents P<0.01.

Fig. 1 is influence (data be derived from table 1-2 mean) of the present invention combination to normal choleresis rate of change, wherein, it is horizontal Coordinate is time (dividing), and ordinate is rate of change (%).

The influence of abnormal choleresis caused by choleretic is given in the present invention combination of experiment 2. to single

This experiment eliminates influence of the acid medium to choleresis on the basis of above-mentioned experiment 1, so experiment is no longer set Medium of citric acid group.By 30 cavys, 3 groups are randomly divided into by body weight：Negative 20 control groups, model control group, invention combination group, Every group 10, before experiment fasting can't help water 12 hours, each group animal is with after 20% Ethylurethanm 1mL/100g.bw intraperitoneal injection of anesthesia Make ductus choledochus insertion silicone tube operation.Collected after the completion of operation, measure bile volume to observe the stability of choleresis.It is tested Thing is using clinical plan dosage as Main Basiss.The dose,equivalent that cavy is converted into according to body surface area is 1.17g crude drugs/kg, is taken 0.52g crude drugs/mL SLJ oral liquids, i.e. 5.2g crude drugs/kg is administered by 1mL/100g.(90 points after choleresis is steady Clock), by table 2-1 settings, duodenum gives tested material respectively.

Table 2-1 present invention combination influences experiment dosage regimen to abnormal choleresis caused by single-dose

As shown in table 2-1, this experimental administration method is 30 points after single gives choleretic urso Clock gives present invention combination oral liquid again, observes the influence of present invention combination bile abnormal secretion to caused by urso. Negative control group and model control group give purified water for 30 minutes after urso is given as control.

Every group since being given tested material, was collected every 30 minutes and accurately measures bile volume, calculated by following equation Choleresis courage rate of change.

Choleresis rate of change (%)=100 (B-A)/A

A：Preceding 30 minutes choleresis；B：30 minutes choleresis afterwards.Period choleresis after negative value represents The choleresis at more previous time point reduces.Increase on the occasion of representing.

It is poor different in nature (Spss softwares, Nonparametric Analysis) to collect the processing that takes statistics of each experimental group data

As a result (table 2-2) is shown：Choleretic urso is being given in model control group and present invention combination Afterwards, choleresis substantially increases, and endocrine in 30 minutes adds 45.1% and 50.7% (P respectively<0.01) it is different, to cause bile Often secretion.Hereafter two groups of secretory volumes gradually reduce on the basis of increasing, but the choleresis that combines of the present invention reduce intensity and Speed is significantly greater than model control group, (i.e. to 30-60 points after present invention combination during 60-90 minutes after to urso Clock), choleresis reduces 34.5%, and is 18.9% with period model control group choleresis rate of change, and difference is extremely aobvious Write (P<0.01).As a result present invention combination is indicated for the increased antagonism of abnormal choleresis.Testing identical comparison Time, negative control group choleresis by gentle reduction is kept, have no obvious fluctuation all the time.

Influence (%) (x ± sd) of the table 2-2 present invention combinations to the rate of change of abnormal choleresis caused by single-dose

Note："-" represents the choleresis drop at the latter period, the choleresis time point more previous time point It is low.Compared with negative control group, * represents P<0.05；* represents P<0.01.Compared with model control group, △ represents P<0.05.

(it is equal that data are derived from table 2-2 for influence of Fig. 2 present invention combinations to abnormal choleresis rate of change caused by single-dose Number).Wherein, abscissa is time (dividing), and ordinate is rate of change (%).

The present invention of experiment 3. combines the influence to repeatedly giving abnormal choleresis caused by choleretic

By 30 cavys, 3 groups are randomly divided into by body weight：Negative control group, model control group, combination group of the present invention, every group 10, before experiment fasting can't help water 12 hours, each group animal is total with making after 20% Ethylurethanm 1mL/100g.bw intraperitoneal injection of anesthesia Bile duct insertion silicone tube operation.Collected after the completion of operation, measure bile volume to observe the stability of choleresis.Tested material with Clinical plan is Main Basiss with dosage.The dose,equivalent that cavy is converted into according to body surface area is 1.17g crude drugs/kg, takes 0.52g Crude drug/mL SLJ oral liquids, i.e. 5.2g crude drugs/kg is administered by 1mL/100g.After choleresis is steady (90 minutes), By table 3-1 settings, duodenum gives tested material respectively.

Table 3-1 present invention combination influences experiment dosage to abnormal choleresis caused by multiple dosing

By table 3-1 packet and dosage arrangement, the tested material of each group animal gives time and order being arranged into by table 3-2 OK.Thus, model control group and combination group of the present invention gave choleretic bear in every 30 minutes respectively since 0 minute Deoxycholic aicd, it is intended to make two groups of animals keep higher abnormal choleresis during experiment.Combination group of the present invention and model pair According to unlike group：First, (0 minute) gives after urso 30 minutes, and property gives combination S LJ mouths of the present invention again Take liquid.Negative control group then gives purified water.

Table 3-2 present invention combination influences experiment dosage regimen to abnormal choleresis caused by multiple dosing

Every group since being given tested material, was collected every 30 minutes and accurately measures bile volume, calculate each bleeding point Bile volume (mL, X ± SD), data take statistics processing, compare each group choleresis difference (Spss softwares, nonparametric point Analysis).

And calculate choleresis courage rate of change by following equation.

Choleresis rate of change (%)=100 (B-A)/A

A：Preceding 30 minutes choleresis；B：30 minutes choleresis afterwards.Period choleresis after negative value represents The choleresis at more previous time point reduces.Increase on the occasion of representing.

It is poor different in nature (Spss softwares, Nonparametric Analysis) to collect the processing that takes statistics of each experimental group data

As a result (table 3-3) is shown：Choleretic urso is being given in model control group and present invention combination Afterwards, choleresis substantially increases, and endocrine in 30 minutes increases respectively to peak, (adds 34.1% and 41.9% (P<0.01) It is shown in Table 3-4), cause bile abnormal secretion.Hereafter model control group secretory volume maintains high-order secretion on the basis of increasing, Display repeatedly gives choleretic urso and the continuation of choleresis is acted on.But the bile that the present invention combines Secretory volume, after being peaked with the model control group same period, although repeatedly giving choleretic ursodeoxycholic Acid, its choleresis significantly reduce (P after SLJ oral liquids are given 60 minutes<0.01), and continue to be reduced to it is right with feminine gender According to a group no significant difference, more than 120 minutes action time (P<0.01).In addition, upon administration 90 minutes when the present invention combination not Only show the effect of extremely obvious confrontation choleretic, also show be better than the choleresis of negative control group from Right reduction effect, present invention combination choleresis reduce -27.1% ± 12.7%** △ △ (table 3-4, P<0.01).This knot Fruit with described in example 1 and 2 to connect fruit consistent.As a result it is different not only for (caused by single-dose) transience to indicate present invention combination Normal choleresis increase has antagonism, and has antagonism to the increase extremely of continuation (caused by multiple dosing) bile, It is stable and action time is lasting.The identical relatively time is being tested, negative control group choleresis is gently subtracted by holding all the time It is few, have no obvious fluctuation.

Influence (mL, x ± sd) of the table 3-3 present invention combinations to abnormal choleresis caused by multiple dosing

Note：Compared with negative control group, * represents P<0.05；* represents P<0.01.

Compared with model control group, △ represents P<0.05.

Influence (%) (x ± sd) of the table 3-4 present invention combinations to abnormal choleresis rate of change caused by multiple dosing

Note："-" represents the choleresis drop at the latter period, the choleresis time point more previous time point It is low.Compared with negative control group, * represents P<0.05；* represents P<0.01.Compared with model control group, △ represents P<0.05.

(it is equal that data are derived from table 3-3 for antagonism of Fig. 3 present invention combinations to abnormal choleresis caused by multiple dosing Number), wherein, abscissa is time (dividing), and ordinate is secretory volume (ml).

(it is equal that data are derived from table 3-4 for influence of Fig. 4 present invention combinations to abnormal choleresis rate of change caused by multiple dosing Number), wherein, abscissa is time (dividing), and ordinate is rate of change (%).

The Journal of Sex Research safe to use that embodiment 4, the present invention combine

4.1 acute toxicity testing

Combination S LJ oral liquids of the present invention, it is (for the 1.33 of clinical application concentration per milliliter contained 0.966g to increase concentration Times).Mouse Kunming 21.3 ± 1.7g of kind, male and female half and half, health is qualified, is tested through prerun, mouse is in Cmax, maximum capacity Under, oral invention combination S LJ oral liquids, animal can not measure lethal toxicity dosage without death in 3 days.According to《It is Chinese medicine, natural Acute toxicity investigative technique guideline》Pertinent regulations, therefore change survey and maximal tolerance dose is administered orally.Take Kunming mouse (21.3 ± 1.7g), male and female half and half, totally 20 mouse, take invention combination S LJ oral liquids 30ml/kg (body weight), three times per day, 87g (crude drug)/kg (body weight), Continuous Observation 7 days are taken within i.e. 24 hours altogether.Animal is without death in 7 days, and general behavior activity is just Often, animal is put to death after 7 days, cuts open and test and the histoorgans such as the heart, liver, spleen, lung, kidney, adrenal gland are visually observed, have no obvious Lesion.As a result show, show more than 300 times of the maximum administration dosis tolerata behaviour dosage of invention combination S LJ oral liquids.Belong to nontoxic Class level of security.

4.2 long term toxicity test

Press《Chinese medicine, natural drug long term toxicity investigative technique guideline》Regulation, select healthy WISTAR big white mouse 120 Only, body weight 80-90g, male and female half and half, after raising one week, 4 groups of (i.e. high, medium and low dosage combinations are randomly divided into by sex and body weight Control group), administration group animal presses 17.4g (crude drug/kg body weight, 60 times of people's dosages), 8.7g (crude drug/kg body weight, 30 times of people respectively Dosage)；1.45g (crude drug/kg body weight, 5 times of people's dosages).With the daily gastric infusion of invention combination S LJ oral liquids once, continuously Administration 60 days, control animals give isometric distilled water；Each group animal is routinely raised.Weigh within every 10 days during administration Once, successive administration is after 30 days, and each group, which is killed, to be taken after 10 rats and administration 60 days each group animal to kill to take 20.Two batches animal enters (Hb, RBC, WBC and WBC classify for row Liver and kidney function (GPT, total protein, albumin, globulin, urea nitrogen, creatinine) and blood picture Count) check.And pathology morphological examination is made to the vitals of 120 rats, emphatically to the heart, liver, spleen, lung, kidney, adrenal gland Visually observed, weighed Deng histoorgan, and take each one piece of the tissue of above-mentioned organ immediately, put into 10% formalin It is fixed, conventional dehydration, FFPE, section, HE dyeing, Pathomorphology damage is observed under an optical microscope.Result of the test Show.The high, medium and low Three doses of invention combination S LJ oral liquids continuously to big white mouse gastric infusion 30 days and 60 days after, to animal Grow, hepatic and renal function and hemogram checking without overt toxicity detrimental effect, and through PATHOMORPHOLOGICAL OBSERVATION OF PULLORUM, the animal heart, The important organs such as liver, spleen, lung, kidney, adrenal gland, without obvious Pathomorphology damage phenomenon, show that long-term takes invention The security that combination S LJ oral liquids use.

The Clinical practice study on the efficiency that embodiment 5, the present invention combine

1st, case general information：

Biliary tract dyskinesis case 60, male 35 people, the people of female 25.It is randomly divided into two groups, every group each 30.The course of disease is most short by one Year, most long 20 years, treatment group's average age 51 years old, control group average age 48 years old.The distribution of patient's ordinary circumstance is shown in Table 5-1.

Two groups of patient's ordinary circumstances of table 5-1 compare

2nd, case diagnosis standard

Diagnosis and efficacy assessment standard are with reference to documents below.

【James Toouli Current Treatment Options in Gastroenterology09/2002；5 (4):285-291.DOI:10.1007/s11938-002-0051-9】。

【Brown,M R；Siafakas,C G；Ryan,C K；Pegoli,W；Miller, T L, Biliary Dyskinesia:A Cause of Recurrent Abdominal Pain,Diagnosis By Cck Cholescintigraphy, Relief of Pain After Cholecystectomy, Journal of Pediatric Gastroenterology&Nutrition:October1998-Volume27-Issue4- p470, Annual Meeting of the North American Society for Pediatric Gastroenterology and Nutrition； Orlando,October22-24,1998】。

【Tanaka directly shakes:The disease of biliary dyskinesia should be with diagnosis internal medicine 6, (3):455,1990, Jianming Zhou is translated selected passages, Hu Ji Sparetime school for adults, Japan medical science introduce 99.Year o. 11th of volume 11, page 515】.

【Hogan WJ, Geenen JE., Biliary dyskinesia.Endoscopy.1988Aug；20Suppl1: 179-83.】。

Through main suit, sign, ultrasonic wave (B ultrasound) checks, possesses following indication, and be diagnosed as biliary tract dyskinesis case：

(1) ultrasonic wave (B ultrasound), which checks, excludes cholelithiasis, inflammation, tumour；

(2) the right Upper abdominal pain of recurrent exerbation, greasy food is tired, and the factor such as insomnia induces, and spasmolysis medicine can be alleviated；

(3) upper right abdominal pressure pain；

(4) upper abdomen continues burn feeling, can also appear as pain after breastbone, can aggravate after the meal；

(5) simultaneous phenomenon (belch, sour regurgitation, Nausea and vomiting, anorexia and become thin)

3rd, treatment method

The oral oral liquid of the present invention for the treatment of group, each 15ml, 2 times a day；Or 30ml is taken during pain, daily no more than 2 It is secondary, 30 days as one therapeutic course.

Control group is oral " XIAOYAN LIDAN PIAN ", and 4 tablets once, takes 3 times daily, 30 days as one therapeutic course.

Other medicines, including Chinese medicine, Chinese patent drug etc. are disabled during observation.

4th, curative effect determinate standard

Symptom integral before treatment：

The right Upper abdominal pain of 50 points-recurrent exerbation of product, greasy food is tired, and the factor such as insomnia induces, and spasmolysis medicine can delay Solution.

20 points-upper right of product abdominal pressure pain.

15 points-upper abdomen of product continues burn feeling, can also appear as pain after breastbone, can aggravate after the meal.

15 points-simultaneous phenomenon of product (belch, sour regurgitation, Nausea and vomiting, anorexia and become thin).

Total score 100

Symptom integral after treatment (remission integration declines)：

It is effective：Symptom integral declines more than 1/2.

Effectively：Symptom integral declines 1/3-1/2.

It is invalid：Symptom product integration is declined by less than 1/3.

Aggravate：Symptom aggravates on the contrary without alleviation.

Table 5-2 oral liquid treatment biliary tract dyskinesis case curative effects of the present invention compare

And conclusion as a result

Treatment group has 4 not to be collected into complete data, is deleted, and effectively counts case 26.This oral hair for the treatment of group Bright effective 23 of oral liquid, obvious effective rate 88.5%, effective 3, total effective rate 100%.And effective 10 of control group, obvious effective rate 33.3%, effective 15, invalid 5.Therapeutic effect is relatively shown in Table 5-2, the results showed that, oral liquid of the present invention moves to treatment biliary tract Power obstacle has obvious curative effects, especially to right Upper abdominal pain caused by biliary tract dyskinesis, upper right abdominal pressure pain, upper abdomen continue burn feeling and Other simultaneous phenomenons are relieved effect, and its effect is better than street drug " XIAOYAN LIDAN PIAN ".

Claims (9)

1. a kind of pharmaceutical composition for treating courage relevant disease is preparing suppression hypercholia or treatment biliary tract dyskinesis Purposes in medicine, it is characterised in that：Composition is made up of the medicine of following portions by weight：Emblic 10-0.5 parts；Myrobalan 7- 0.1 part；Terminaliae billericae,fructus 8.5-0.1 parts.

2. purposes according to claim 1, it is characterised in that composition is made up of the medicine of following portions by weight：Emblic 4.0-2.0 parts, myrobalan's 3.2-0.5 parts, terminaliae billericae,fructus 2.8-0.4 parts.

3. a kind of prepare as claimed in claim 1 or 2 suppresses to treat in hypercholia or treatment biliary tract dyskinesis medicine The preparation method of courage relevant disease pharmaceutical composition,

It is characterized in that comprise the following steps：

(1) weigh each raw material by the proportion of composing of claim 1 or 2 to mix, add 6-20 times of decocting of raw material gross weight to boil 2 times, 1 hour every time, filtering, merging filtrate, put in vacuum concentration pot, 60 DEG C, 0.02mpa it is relatively close under the conditions of being concentrated under reduced pressure into 20 DEG C Spend the extract solution for 1.10-1.25；

(2) step (1) extract solution is prepared into oral liquid or capsule.

4. preparation method according to claim 3, it is characterised in that：

Step (1) extract solution adds agar, honey to mix in right amount, and 4 DEG C are placed 48 hours, and filtering, filtrate adds appropriate flavor enhancement, Mix, gabon profit soil is appropriate, mixes, and 4 DEG C are placed 48 hours, are filtered repeatedly, and filtrate is filling, are sterilized, and are examined, and are packed, and are put in storage, system Into oral liquid；

Or, step (1) extract solution add absolute ethyl alcohol to ethanol content reach 70%, fully mix, stand overnight, filter, filter After liquid recovery ethanol, put in vacuum concentration pot, 60 DEG C, relative density is 1.28- under the conditions of 0.02mpa is concentrated under reduced pressure into 20 DEG C 1.40 thick paste；By mass fraction 7:1:1 to take starch, dextrin, Icing Sugar be auxiliary material, and thick paste mixing granulation, less than 60 DEG C dryings, Purification, crush, sieving is filling that capsule is made.

5. purposes according to claim 1 or claim 2, it is characterised in that：Described pharmaceutical composition is preparing treatment biliary tract power barrier Application in pain medication caused by hindering.

6. purposes according to claim 1 or claim 2, it is characterised in that：Described pharmaceutical composition is preparing treatment biliary tract power barrier Application in upper right abdominal pressure pain medicine caused by hindering.

7. purposes according to claim 1 or claim 2, it is characterised in that：Described pharmaceutical composition is preparing treatment biliary tract power barrier Hinder the application in caused biliary tract, Oddi sphincter function disorder medicines.

8. purposes according to claim 1 or claim 2, it is characterised in that：Described pharmaceutical composition is preparing treatment biliary tract power barrier Application in bile reflux gastritis medicine caused by hindering.

9. purposes according to claim 1 or claim 2, it is characterised in that：Described pharmaceutical composition is preparing treatment courage external form biliary tract Application in dyskinesis medicine.