CN105168279B - Application of the pill of Eight Treasures in preparation treatment primary sclerotic cholangitis drug - Google Patents

Abstract

The invention discloses the new applications of pill of Eight Treasures and its preparation, especially the application in preparation treatment primary sclerotic cholangitis drug.The effect of pill of Eight Treasures and its preparation, is used for wider field by the present invention, opens a kind of new Chinese medicine treatment method for treatment primary sclerotic cholangitis.

Description

Application of the pill of Eight Treasures in preparation treatment primary sclerotic cholangitis drug

Technical field

The present invention relates to the new application of pill of Eight Treasures, especially pill of Eight Treasures and its preparation to treat primary sclerotic gallbladder in preparation Application in pipe inflammation drug.

Background technique

The main component of pill of Eight Treasures is cow-bezoar, snake gall, antelope's horn, pearl, Radix Notoginseng, Moschus etc., existing to be applied to damp and hot accumulate Fever caused by knot, jaundice, dark urine, nausea and vomiting are indigestion and loss of appetite, hypochondriac pain abdominal distension, yellowish fur or thick greasy extra dry white wine or damp invasion of lower energizer Caused urethra scorching hot shouting pain, lower abdominal distention pain and spreading venereal diseases toxicity hepatitis, acute cholecystitis, the infection of acute urinary system etc. are shown in There is above-mentioned patient.

Primary sclerotic cholangitis (PSC) is a kind of chronic cholestatic hepatopathy, with the progressive inflammation of bile duct, fibre Dimensionization and multiple stenosis are major pathologic features.The pathogenesis of PSC not yet illustrates, may with autoimmune function disorder, Gene Susceptibility and bile duct epithelial cell dysfunction are related.Medication effect is undesirable at present, existing several frequently seen Treatment drug it is as follows:

(1) UDCA(ursodesoxycholic acid): UDCA is the drug of effective treatment PBC a kind of, therefore is recommended as PSC treatment Drug candidate.The initial stage nineties, one small pilot study was shown, 10~15 mg/(kgd are used in PSC patient) agent The UDCA of amount is treated, and biochemical and some cases histologies are improved.Another it is prior research be 1997 by The doubleblind-placebo Comparative study that 105 patients of Lindor report participate in, the dosage using UDCA are 13~15 mg/ Kg continue for 2 years altogether.Liver serum test project is improved as the result is shown, but symptom is without substantially changeing, prior It is, according to disease classified estimation, not improve in terms of liver histological.

One research patient in group's number of Scandinavia reaches 219 people, and treatment cycle was up to 5 years, the drug agent that uses Amount is 17~23 mg/(kgd), the survival rate of UDCA treatment group is improved compared with placebo as the result is shown, but is compared compared with control group, Statistically there was no significant difference.Compared with other researchs, biochemical responses relative mistake, prompt may with part study population according to From the poor correlation of property.

Recently, what is carried out in 150 patients of a multicenter uses 28~30 mg/(kgd of large dosage UDCA) last 5 The research failure in year, although increasing UDCA treatment group simultaneously because biochemical character is improved in entire treatment group and existing The risk of Primary endpoint is reached in some progressive diseases, this includes liver transfer operation and cirsoid progress.In this way, UDCA drops The effect of the relevant liver diseases progress of low PSC is still unclear that the UDCA of high dose may be to terminal illness nocuousness.

(2) immunosuppressor and other preparations: glucocorticoid and other immunosuppressor are not shown to disease Activity or the final result of PSC play a role in improving.Small random, placebo or pilot study are once to immunosuppressor Work be used as research, these drugs include prednisone, cloth ground a kind of apple moral, imuran, ciclosporin A, methotrexate, Ta Kemo Department, pentoxifylline, colchicin and penicillamine etc..Not evidence suggests these drugs are effective, so not recommending for treating Classical PSC.

To sum up, acquired data shows the mg/d of UDCA(15~20) improve serologic test index and prognosis substitution refers to Mark, but being benefited to survival rate does not prove, limited data does not make special recommendation UDCA as PSC general treatment medicine The license of object.Glucocorticoid and other immunosuppressor in adult PSC treatment it is not recommended that apply.

Summary of the invention

The purpose of the present invention is to provide the new application of pill of Eight Treasures, i.e. pill of Eight Treasures treats primary sclerotic bile duct in preparation Application in scorching drug provides new therapeutic agent for primary sclerotic cholangitis.

The invention discloses application of the pill of Eight Treasures in preparation treatment primary sclerotic cholangitis drug.

Wherein, the pill of Eight Treasures selectively adds customary adjuvant, and routinely clinically acceptable preparation, institute is made in technique The preparation stated includes pastille, capsule, tablet, granule, pill, powder.

Wherein, the pill of Eight Treasures day dose is 1.0~3.0g.

Primary sclerotic cholangitis (PSC) is a kind of chronic cholestasis autoimmune liver disease, it is characterized in that liver Inside and outside bile duct inflammation and fibrosis, and then lead to multifocal stenosis of bile duct.PSC clinical manifestation variability is big, slowly concealment of falling ill. Early stage non-evident sympton, early diagnosis have difficulties.Be mainly shown as when PSC patient assessment repeated relapsing jaundice, it is out of strength, receive Difference, pruitus, hepatalgia, syntexis, fatigue, hepatomegaly, abdominal distension or with chilly, fever etc..

Primary sclerotic cholangitis is belonged into " hypochondriac pain ", " jaundice ", " accumulation ", " tympanites ", " consumptive disease " in traditional Chinese medicine Equal scopes.It is clinically mainly shown as the symptoms such as tired, the out of strength, itch of mind, jaundice, there is chronic delay, obstinate refractory and repeatedly The features such as breaking-out.The basic interpretation of the cause, onset and process of an illness of PSC is " asthenia in origin and asthenia in superficiality ", " weakened body resistance to hold the stasis of blood under the arm ".Liver controlling conveyance and dispersion, item reach, store blood, stagnation of liver qi, gas The machine stasis of blood is stagnant, hematogenous blockage and cause blood stasis.Damp evil accumulates coke in resistance, and taste, which lose, is good for, and irritability stasis, catharsis is unfavorable, and the catharsis of gallbladder sweat is caused to lose Often, the road bile Bu Xunchang, excessive skin, bladder of betting, and sending out is that mesh is yellow, skin is yellow, urine Huang illness.Primary treatments are Alleviate the symptom that chronic bile smoulders, regulating qi to disperse stagnation, strengthening the spleen and replenishing qi improve microcirculation in liver, promote siltation Bile metabolism, expansion Narrow bile duct lumen.

Cow-bezoar is mainly the cholecystolithiasis of ox or buffalo, and minority is the calculus in bile duct or common hepatic duct, and modern pharmacology is ground Study carefully cow-bezoar and mainly contain cholic acid, deoxycholic acid, cholesterine and bilirubin, taurine etc., taurine is that one kind is converted by cystine And the beta amino acids of the sulfur-bearing come, it is human body condition essential amino acid, largely distribution in the cell, has very extensive for it Biological effect, liver is the important target organ of taurine, research confirm taurine have it is anti-oxidant and inhibit Kupffer Cell Activation has prevention effect to LSP hepatotoxicity wind agitation, has certain curative effect to hepatic lesion, chronic liver disease.

Microelement, bile acid, glycine and taurocholate rich in etc., the microelement in snake gall in snake gall Zn, Cu, Fe and macroelement Ca, Mg, their active functions to internal a variety of enzymes, to the synthesis of nucleic acid and protein, immune Process plays the role of direct or indirect, may additionally facilitate the reparation of epithelial cell, increases cell division, and T cell increases, activity Enhancing, to be played regulatory role to organism immune function.Snake gall can be reduced liver cell inner cell pigment P₄₅₀ Content reduces four The free radical that chlorination carbon metablism generates, to generate protective effect to liver.

Antelope's horn nature and flavor are salty-cold, return liver, the heart channel of Hang-Shaoyin, tool suppressing hyperactive liver for calming endogenous wind, heat-clearing is relieving convulsion, the function of removing toxic substances.

Natural peral calcium carbonate 91.72%, organic matter 5.94%, water 2.23% indicate in " dictionary of medicinal plant ": pearl tool There are arresting convulsion of calming the nerves, shade removing, solution taking poison and growing muscle due and other effects.

Radix Notoginseng is the dry root of araliaceae ginseng plant Radix Notoginseng, sweet in flavor, slight bitter, warm-natured, there is cholagogue, removing jaundice, drop enzyme The effects of, the plasma albumin of patients with chronic liver can be improved.Notogineng Extract has significant decrease serum bilirubin, promotes gallbladder Juice secretion.

Moschus nature and flavor are pungent, warm, return heart the spleen channel, and main chemical compositions have macrocyclic ketone class compound, pyridine compounds and their, steroidal Class compound, polypeptide protein compound, fatty Halogenated-hydrocarbons and some inorganic elements etc..Water solubility in Moschus Polypeptide protein class can have an impact functions of neutrophils, to play anti-inflammatory effect.

The present invention develops the new application different from script curative effect on the application foundation of existing pill of Eight Treasures and its preparation Field, above several main components play its respective effect and synergistic effect, and by clinical test, treated effect is high, A kind of new Chinese medicine treatment method is opened for prevention and treatment primary sclerotic cholangitis.

Specific embodiment

In order to make the objectives, technical solutions, and advantages of the present invention clearer, with reference to embodiments, to the present invention It is further elaborated.

Embodiment 1

Commercially available eight treasures (choice ingredients of certain special dishes) capsule (national drug standard Z10940006, Xiamen Chinese Medicine Co., Ltd's production) is taken, every contains eight treasures (choice ingredients of certain special dishes) 0.25~0.3g of pellet is used to prepare in treatment primary sclerotic cholangitis drug, when patient takes, daily 2~3 times, and every time 2 Grain.

Embodiment 2

It takes commercially available pill of Eight Treasures pastille (national drug standard Z10940005, Xiamen Chinese Medicine Co., Ltd's production) to crush, is added normal Tablet is made in rule auxiliary material, contains pill of Eight Treasures 0.5g in every tablet preparation, is used to prepare in treatment primary sclerotic cholangitis drug, When patient takes, 3 times a day, 1~2 every time.

Embodiment 3

It takes commercially available pill of Eight Treasures pastille (national drug standard Z10940005, Xiamen Chinese Medicine Co., Ltd's production) to crush, is added normal Granule is made in rule auxiliary material, contains pill of Eight Treasures 0.6g in every bag of particle, is used to prepare treatment primary sclerotic cholangitis drug In, when patient takes, 3 times a day, 1 bag every time.

Embodiment 4

It takes commercially available pill of Eight Treasures pastille (national drug standard Z10940005, Xiamen Chinese Medicine Co., Ltd's production) to crush, is added normal Pill is made in rule auxiliary material, contains pill of Eight Treasures 0.5g in every pill, is used to prepare in treatment primary sclerotic cholangitis drug, When patient takes, 3 times a day, 1~2 every time.

Embodiment 5

It takes commercially available pill of Eight Treasures pastille (national drug standard Z10940005, Xiamen Chinese Medicine Co., Ltd's production) to crush, is added normal Powder is made in rule auxiliary material, contains 0.5~0.8g of pill of Eight Treasures in every bag of powder, is used to prepare treatment primary sclerotic cholangitis medicine In object, when patient takes, 3 times a day, 1 bag every time.

Further verifying explanation is done to the present invention below in conjunction with clinical trial.

1, diagnostic criteria

(1) chronic cholestatic, serum levels of ALP are greater than 2 times of the reference value upper limit, and the time was more than 6 months；

(2) there is inflammatory bowel disease medical history；

(3) MRC or ERCP checks the beading performance that prompt liver is outer, stones in intrahepatic bile duct has multiple stenosis expansion；

(4) liver impedance rheograph shows occlusion of bile duct, bile duct surrounding annulus, bile duct rareness or biliary cirrhosis；

(5) there are pANCA and low titre ANA, smooth muscle antibody (ASMA).

2, index of assessment of curative effect:

(1) pretherapy and post-treatment clinical symptoms improve situation；

(2) decline of serum levels of ALP level, the improvement of liver function；

(3) improvement of liver histological.

3, clinical trial process

2011.04-2014-07 period tracks case 14 of primary sclerotic cholangitis.14 sufferers are divided into two Group, two groups of ages, gender, the cause of disease, courses of disease evenly distribute.

Control group: case 7, using conventional therapy.

Treatment group:, taking pill of Eight Treasures by 7 on the basis of conventional therapy, during medication, non-drug combination, pill of Eight Treasures is used Mode is 0.6 gram/times, 3 times a day, course for the treatment of June.

4, experimental result

(1) pretherapy and post-treatment clinical symptoms improve situation: the clinical symptoms improvement situation of 7 treatment groups is good compared with control group, Pretherapy and post-treatment cardinal symptom integral is shown in Table 1.

(2) liver function is mainly shown as that ALP, GGT are increased.ALP averagely increases 4 times before 14 patients treat, and GGT is average 6 times are increased, pill of Eight Treasures (is taken 6 months) by treatment group on the basis of conventional therapy, have 3 ALP, GGT to restore to just in 7 patients Ordinary water is flat, remaining 4 ALP, GGT averagely increase 1~2 times.ALP averagely increases 2~3 times in 7 patients of control group, and GGT is average Increase 2~4 times.It can be seen that the effect for the treatment of group is substantially better than control group.

5, typical case:

The old * * of patient, male, 63 years old, because of intermittent out of strength, right epigastric discomfort, yellow urine 1 month, itch half a month, syntexis half Year, patient is in September, 2012 medical, no gall stone, the operation on biliary tract history in addition to cholecystectomy, B ultrasound inspection to hospital outpatient Prompt liver and spleen pancreas no abnormality seen is looked into, gallbladder wall slightly thickens, liver function: 121 U/ L of alanine aminotransferase (ALT), 68 U/L of aspartate amino transferase (AST), 778 U/ L of gamma glutamyl transpeptidase (GGT), total bilirubin (TBiL) 33 μm of ol/L, bilirubin direct (DBiL) 21 μm of ol/L, alkaline phosphatase (ALP) 211U/L.First, second, third, type hepatitis Malicious blood serum designated object is negative.Cholangiography inspection is carried out, the beading that liver is outer, stones in intrahepatic bile duct has multiple stenosis expansion is prompted Performance, Patient height 167cm, 67 kg of weight are diagnosed as primary sclerotic cholangitis.Give 0.6 gram/times of pill of Eight Treasures, one day 3 times, course for the treatment of June, after medication June, patient is out of strength, right epigastric discomfort, yellow urine, pruritis disappear, and sign increases by 5.2 kilograms, Check liver function: ALT25.0 U/L, AST19 U/L, GGT141 U/L, TBiL11.1 μm of ol/L, DBiL7.6 μm of ol/ L, ALP110 U/L.Ultrasound diagnosis prompt gallbladder wall slightly thickens mitigation, and cholangiography shows that biliary tract diffusivity " beading " changes Change is mitigated, and patient voluntarily continues intermittence and takes pill of Eight Treasures, and follow-up 27 months, private prosecution symptom did not recurred again.

The foregoing is only a preferred embodiment of the present invention, anyone skilled in the art exists The invention discloses technical scope in, any changes or substitutions that can be easily thought of, should be covered by the protection scope of the present invention.

Claims (2)

1. application of the pill of Eight Treasures in preparation treatment primary sclerotic cholangitis drug, the pill of Eight Treasures selectively add routine Auxiliary material, routinely technique is made clinically acceptable preparation, the preparation include pastille, capsule, tablet, granule, Pill, powder.

2. application as described in claim 1, which is characterized in that the pill of Eight Treasures day dose is 1.0g~3.0g.