Background technology
Alcoholic hepatitis is a Clinical typing of alcoholic liver disease, it is one group of clinical pathology syndrome that a large amount of necrosis of hepatocyte in a short time causes, can to occur in or without on the basis of liver cirrhosis, main manifestations is Serum ALT, AST raises and serum total bilirubin obviously increases, and can raise with heating, peripheral blood neutrophil.
The topmost clinical manifestation of alcoholic hepatitis occurs jaundice rapidly, and it is of flaccid muscles etc. that other sings and symptoms comprises heating, ascites, near-end, and serious symptom alcoholic hepatitis patient can occur hepatic encephalopathy.Usually, the liver of alcoholic hepatitis patient increases, liver touches a tender spot the positive.Laboratory research shows, and the sex expression of alcoholic hepatitis patient characteristic is: the normal >2 of AST times Upper Limit of Normal Value, but little >300U/ml.And Serum ALT is lower, the usual >2 of AST/ALT, but this feature does not have specificity and a susceptiveness.Peripheral blood leucocyte, neutrophil count, serum total bilirubin and INR (intemationalnormalizedratio.INR) raise simultaneously.Serum creatinine level raises, and indication prognosis mala, because this usually imply that the generation of hepatorenal syndrome and even closing on of death.
Liuwei Anxiao is loose is the classical proved recipe of Tibetanmedicine, and the clinical practice history in existing more than 100 years, is made up of Radix Inulae, Radix Et Rhizoma Rhei, Rhizoma Kaempferiae, calcine calcite, Fructus Chebulae, Tronae so far.Function cures mainly as stomach function regulating spleen invigorating, consumer product dredge stasis, promoting blood circulation and stopping pain.For incoordination between the spleen and stomach, in stagnant, stop caused stomachache distension, dyspepsia, constipation dysmenorrhea.LIUWEIANXIAO JIAONANG with prescription is recorded in the version Pharmacopoeia of the People's Republic of China in 2010.
Through patent retrieval, with Liuwei Anxiao lively stock Patents totally 7, wherein 1 design patent, 6 patents of invention.In patent of invention, preparation class has 5, has the preparation method of pill, tablet, nanometer formulation, Traditional Chinese medicine preparation-Liuwei Anxiao Pills, gastric motility Chinese medicine preparation respectively.In tablet, pill, technology is put forward in main employing steaming, effectively remains volatile ingredient, improves medicine stability.Nanometer formulation mainly adopts nanometer medical material to be made by microwave extracting, concentrating under reduced pressure, supersonic jet technology spraying dry.Traditional Chinese medicine preparation-Liuwei Anxiao Pills changes sterilization process, adopts Co 60 irradiation process.Gastric motility Chinese medicine preparation adopts that percolation, the technology such as concentrated, dry are refining to be formed, enhancing gastric motility.Quality control class has 1, adopts TLC method to differentiate each medical material in prescription, and adopts HPLC method to carry out assay to emodin, chrysophanic acid, chrysophanol, physcione, aloe-emodin.
Through consulting the data bases such as Wei Pu, CNKI, retrieve this product pertinent literature 24 sections altogether, wherein clinical practice class has 12 sections, relates generally to the application of the aspects such as constipation, peptic ulcer, gastroesophageal reflux disease, diabetic gastroparesis, pain relieving.Mechanism Study has 1 section.Quality testing class has 10 sections, the main component surveyed is alantolactone, isoalantolactone, emodin and chrysophanol, the method adopted mainly TLC, HPLC, the Spectrophotometric Determination anthraquinone component wherein used in Quantitative Analysis of Anthraquinon in Liuwei ' anxiao Capsule document is more novel.Produce processing procedure 1 section, its document is that in Ma Nuoxi decoction particles, Radix Inulae soak by water controls the impact on alantolactone content.
Above-mentioned patent and document etc. have no the correlational study report of Liuwei Anxiao pharmaceutical composition and the application of preparation in preparation treatment alcoholic hepatitis medicine thereof.
Summary of the invention
The object of this invention is to provide Liuwei Anxiao pharmaceutical composition and the application of preparation in preparation treatment alcoholic hepatitis medicine thereof.Technical scheme of the present invention is as follows:
Liuwei Anxiao pharmaceutical composition and the application of preparation in preparation treatment alcoholic hepatitis medicine thereof, wherein said Liuwei Anxiao pharmaceutical composition is made up of the crude drug of following weight portion:
Radix Inulae 50 weight portion, Radix Et Rhizoma Rhei 200 weight portion, Rhizoma Kaempferiae 100 weight portion, calcine calcite 250 weight portion, Fructus Chebulae 150 weight portion, Tronae 300 weight portion.
Described Liuwei Anxiao pharmaceutical composition and preparation thereof are according to crude drug formula, add the various adjuvants that pharmaceutics allows after crushed, make the tablet on pharmaceutics, granule, capsule, powder or pill.
Described Liuwei Anxiao pharmaceutical composition and preparation thereof prepare active component according to crude drug formula, then add the various adjuvants of pharmaceutics permission, makes the tablet on pharmaceutics, granule, capsule, powder or pill.
The described step preparing active component is as follows:
(1) Radix Inulae, Radix Et Rhizoma Rhei, Rhizoma Kaempferiae, Fructus Chebulae totally 4 taste medical materials are got by crude drug composition, with 70% alcohol reflux 2 times, each extraction time is 2 hours, each solvent load is 10 times of volumes of medical material weight, filters, obtains medicinal residues A and extracting solution A, extracting solution A decompression recycling ethanol, concentrated, drying under reduced pressure, obtains extract A;
(2) step (1) is obtained Tronae that medicinal residues A and crude drug form, calcine calcite that crude drug forms half, by water boiling and extraction 2 times, each 2 hours, each amount of water is 20 times of volumes of calcite weight, filter, extracting solution concentrate drying, obtains extract B;
(3) the calcine calcite of extract A, extract B and crude drug composition half pulverized and mixed, to obtain final product.
Preparing in active component step, described recovery ethanol and concentration technology parameter are 60 ~ 70 DEG C ,-0.07 ~-0.09Mpa; The technological parameter of drying under reduced pressure is 70 DEG C ,-0.08 ~-0.09Mpa, and what other was not specified is the upper usual parameter of pharmacy production or method.
The unit corresponding relation of the weight portion described in this method and parts by volume is g/ml or kg/l.
Described Liuwei Anxiao pharmaceutical composition and preparation thereof and chemical drugs or Chinese medicine or natural drug are preparing the application for the treatment of in alcoholic hepatitis medicine.
Beneficial effect: in the application for the treatment of field of Liuwei Anxiao and preparation thereof, people know it for stomachache distension, and dyspepsia, constipation, the treatment of dysmenorrhea etc., evident in efficacy, clinical practice is extensive.
Instant invention overcomes the technology prejudice of above-mentioned application aspect, found by clinical observation, Liuwei Anxiao pharmaceutical composition and preparation thereof are significantly improved for the biochemical indicator such as AST, ALT, GGT, TBiL of alcoholic hepatitis, and total effective rate is up to more than 75%.
Detailed description of the invention
Following embodiment is for illustrating the preparation of Liuwei Anxiao pharmaceutical composition of the present invention and preparation thereof, but it does not form any restriction to scope of the present invention.
The preparation of experimental example 1, Liuwei Anxiao pharmaceutical composition and preparation thereof
1, prescription: Radix Inulae 75g, Radix Et Rhizoma Rhei 300g, Rhizoma Kaempferiae 150g, calcine calcite 375g, Fructus Chebulae 225g, Tronae 450g;
2, active fraction preparation
(1) Radix Inulae, Radix Et Rhizoma Rhei, Rhizoma Kaempferiae, Fructus Chebulae totally 4 taste medical materials are got by crude drug composition, with 70% alcohol reflux 2 times, each extraction time is 2 hours, each solvent load is 10 times of volumes of medical material weight, filters, obtains medicinal residues A and extracting solution A, extracting solution A decompression recycling ethanol, concentrated, dry, obtain extract A;
(2) step (1) is obtained Tronae that medicinal residues A and crude drug form, calcine calcite that crude drug forms half, by water boiling and extraction 2 times, each 2 hours, each amount of water was 20 times of volumes of calcite weight, filtered, extracting solution concentrate drying, obtains extract B;
(3) the calcine calcite of extract A, extract B and crude drug composition half pulverized and mixed, to obtain final product.
3, preparation
(1) above-mentioned active fraction preparation is become LIUWEIANXIAO JIAONANG 500, every is equivalent to 3.05g medical material, taking dose be one time 1,2 ~ 3 times on the one.
(2) above-mentioned active fraction preparation is become Liuwei Anxiao Film coated tablets 500, every sheet is equivalent to 3.05g medical material, taking dose be one time 1,2 ~ 3 times on the one.
(3) above-mentioned active fraction preparation is become Liuwei Anxiao coated tablet 500, every sheet is equivalent to 3.05g medical material, taking dose be one time 1,2 ~ 3 times on the one.
The clinical observation of experimental example 2, treatment alcoholic hepatitis
Essence for a better understanding of the present invention, below by pharmacological testing and clinical observation test, proves Liuwei Anxiao pharmaceutical composition and the effect of preparation in " treatment alcoholic hepatitis " thereof, its new opplication at pharmaceutical field is described.
Case enters group standard
According in October, 2010 Chinese Medical Association's hepatopathy branch's fatty liver and the diagnostic criteria of alcoholic liver disease of formulating of alcoholic liver disease group enter group:
1) long-term alcohol history, generally more than 5 years, amounts to ethanol amount, male >=40g/d, women >=20g/d, or heavy drinking history (>80g/d) in 2 weeks;
2) aspartate amino transferase (AST) elevation amplitude is obviously greater than alanine aminotransferase (ALT) elevation amplitude, and AST/ALT >=2;
3) hepatitis that other causes of disease cause is got rid of;
4) treat front 1 monthly not with excessively obviously falling enzyme medicine.
Test grouping
MethodsThe cases enrolled is successively divided into two groups at random according to being admitted to hospital: test group 60 example, matched group 60 example, and GP TH all obtains patient and family members agree to, liver Enzyme target no significant difference before the sex of two groups, age, the course of disease, iconography and treatment.
Dosing Regimens: treatments period advises patient's teetotalism, suitably reduces energy intake.Test group patient gives the capsule of experimental example 1, oral, one time 1,3 times on the one, 4 weeks courses for the treatment of.Matched group patient gives former preparation Liuwei Anxiao and falls apart, Jin He Tibetan medicine limited company, and lot number 20121209 is oral, a 3g, 3 times on the one, 4 weeks courses for the treatment of.
Observation index
Curative effect evaluation index
1) sings and symptoms: comprise weak, anorexia, uncomfortable liver area, hepatosplenomegaly etc.
2) liver function: aspartate amino transferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), total bilirubin (TBiL).
Safety indexes
Hematuria is conventional, renal function
Curative effect judging standard
Effective: cardinal symptom and sign disappear, and liver function recovery is normal;
Effective: cardinal symptom and sign are obviously improved, ALT, AST, GGT, TBiL decline 75%;
Invalid: not reach above-mentioned standard.
Obvious effective rate and effective percentage add up to total effective rate.
Statistical procedures:
Application SPSSl7.0 statistical software carries out statistical analysis, the comparison chi-square criterion of two sample rates, and index determining results contrast t checks.Clinical observation result of the test and comparitive study are in table 1, table 2.
Table 1 clinical observation result of the test
Note: compared with before treatment, * * P<0.01
Table 1 result shows: after treatment, 4 liver function indexs of two groups of patients all obtain and extremely significantly improve (P<0.01), and test group effect is more remarkable, point out two kinds of LIUWEIANXIAO ZHIJI all can reduce liver function biochemical indicator, and LIUWEIANXIAO JIAONANG effect prepared by embodiment is more excellent.
Table 2 liang group Clinical efficacy comparison [n]
Group |
n |
Effective |
Effectively |
Invalid |
Total effective rate (%) |
Matched group |
60 |
38 |
8 |
14 |
76.7 |
Test group |
60 |
42 |
11 |
7 |
88.3* |
χ
2inspection, compares with matched group, * P<0.05
Table 2 shows: the Liuwei Anxiao total effective rate that falls apart is 76.7%; Embodiment 1 LIUWEIANXIAO JIAONANG group total effective rate is 88.3%.Prompting Liuwei Anxiao is loose all be can be used for treating alcoholic hepatitis with embodiment 1 LIUWEIANXIAO JIAONANG, and embodiment 1 LIUWEIANXIAO JIAONANG treatment alcoholic hepatitis clinical efficacy is significantly better than Liuwei Anxiao loose (P<0.05).
In addition, before and after patient consumes, renal function, hematuria routine all within normal range, and have no obvious untoward reaction, point out this medicine clinical practice safety high.
Following examples all can realize the effect of above-mentioned experimental example.
Embodiment 1, Liuwei Anxiao are loose, and every gram is equivalent to 1g medical material, for alcoholic hepatitis, and taking dose: every day 2 ~ 3 times, each 3g.
Embodiment 2, LIUWEIANXIAO JIAONANG, every is equivalent to 0.5g medical material, for alcoholic hepatitis, taking dose: every day 2 ~ 3 times, each 6.
Embodiment 3, six component medicine, every sheet is equivalent to 0.51g medical material, for alcoholic hepatitis, taking dose: every day 2 ~ 3 times, each 6.
Embodiment 4, LIUWEIANXIAO JIAONANG, every is equivalent to 3.05g medical material, for alcoholic hepatitis, taking dose be one time 1,2 ~ 3 times on the one.
Embodiment 5, Liuwei Anxiao Film coated tablets, every sheet is equivalent to 3.05g medical material, for alcoholic hepatitis, taking dose be one time 1,2 ~ 3 times on the one.
Embodiment 6, Liuwei Anxiao coated tablet, every sheet is equivalent to 3.05g medical material, for alcoholic hepatitis, taking dose be one time 1,2 ~ 3 times on the one.