CN104095832A - Liver fibrosis prevention medicine and preparation method thereof - Google Patents

Liver fibrosis prevention medicine and preparation method thereof Download PDF

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Publication number
CN104095832A
CN104095832A CN201410322989.8A CN201410322989A CN104095832A CN 104095832 A CN104095832 A CN 104095832A CN 201410322989 A CN201410322989 A CN 201410322989A CN 104095832 A CN104095832 A CN 104095832A
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Prior art keywords
anistree
alcohol
hepatic fibrosis
flos caryophylli
medicine
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CN201410322989.8A
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CN104095832B (en
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易立涛
耿頔
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Huaqiao University
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Huaqiao University
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Abstract

The invention discloses liver fibrosis prevention medicine and a preparation method thereof. The medicine comprises a main effective constituent, namely macranthol; the using dosage of the medicine is 5-50 mg/70 kg weight per day according to the macranthol; the macranthol is wide in source and can be directly extracted and separated from natural substances, and the extraction and the separation are simple and convenient to operate, so that the liver fibrosis prevention medicine produced from the macranthol has the characteristic of low cost; the macranthol, as a natural medicine, has been used for a long time as a traditional medicine, so that the macranthol is high in using safety as a medicine; in addition, the liver fibrosis prevention medicine has a better liver fibrosis prevention effect, so that the macranthol, as a substance for preventing liver fibrosis or related lead compounds, is used for pharmaceutical production, and the source of natural medicine for liver fibrosis prevention is further broadened.

Description

A kind of control hepatic fibrosis medicines and preparation method thereof
Technical field
The invention belongs to liver disease drug technical field, be specifically related to a kind of control hepatic fibrosis medicines and preparation method thereof.
Background technology
The anistree alcohol (Macranthol, its chemical structural formula is as follows) of Flos Caryophylli, molecular formula C 27h 26o 3, molecular weight is 398, CAS:123941-73-1.
The anistree alcohol of Flos Caryophylli is the separated a kind of lignin compound obtaining in Illicium plant bark.At present less to the report of its pharmacological action, only find that it has the effect of neuroprotective unit (Moriyama M, Huang JM, Yang CS, et al.Two new sesquiterpenoids and two new prenylated phenylpropanoids from Illicium fargesii, and neuroprotective activity of macranthol.Chem Pharm Bull.2008; 56:1201-4.) and the effect of Cure of depression (Li J, Geng D, Xu J, et al.Antidepressant-like effect of macranthol isolated from Illicium dunnianum tutch in mice.Eur J Pharmacol.2013; 707:112-9.).
Hepatic fibrosis refers to by connective tissue paraplasm in liver due to various virulence factors, cause diffusivity extracellular matrix in liver excessively precipitation pathological process it be not an independently disease, but many chronic hepatic diseases all can cause hepatic fibrosis.It is the only stage which must be passed by that multiple chronic hepatopathy develops into liver cirrhosis, how hepatic fibrosis is reversed in early days, thereby the formation of blocking-up liver cirrhosis is an important ring of liver function protecting.The traditional Chinese medical science thinks, hepatic fibrosis basic pathogenesis is evil Sheng of just declining, the damp and hot blood stasis of not holding concurrently to the greatest extent, stagnation of liver-QI spleen kidney qi blood deficiency.Stagnation of QI due to depression of the liver, causes blood stasis, and channel tunnel blocks, not nourishing the liver of blood, and key is blood stasis.Blood stasis shows that on the pathology of chronic hepatitis, liver cirrhosis be exactly the formation of hepatic fibrosis.For the treatment of hepatic fibrosis, there is no at present desirable medicine.
Summary of the invention
The object of the invention is to overcome prior art defect, a kind of control hepatic fibrosis medicines is provided.
Another object of the present invention is to provide above-mentioned control hepatic fibrosis medicament preparation.
A further object of the present invention is to provide the application of the anistree alcohol of a kind of Flos Caryophylli in preparation control hepatic fibrosis medicines.
Concrete technical scheme of the present invention is as follows:
A control hepatic fibrosis medicines, comprises the anistree alcohol of main effective ingredient Flos Caryophylli, and its application dose is calculated as 5~50mg/70kg body weight every day with the anistree alcohol of Flos Caryophylli.
In a preferred embodiment of the invention, its application dose is calculated as 5~40mg/70kg body weight every day with the anistree alcohol of Flos Caryophylli.
In a preferred embodiment of the invention, also comprise one or more in filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, solvent, surfactant, flavouring agent, antiseptic, lubricant, sweeting agent and pigment.
In a preferred embodiment of the invention, this control hepatic fibrosis medicines is tablet, capsule, granule or syrup.
Prevent and treat a preparation method for hepatic fibrosis medicines, this medicine is tablet, comprises the steps:
(1) accurately take the component of following weight portion:
(2) by the anistree alcohol of above-mentioned Flos Caryophylli, microcrystalline Cellulose, stearic acid, lactose and micropowder silica gel mix homogeneously, granulation;
(3) in above-mentioned granule, add above-mentioned magnesium stearate, mix rear tabletting, obtain described control hepatic fibrosis medicines.
In a preferred embodiment of the invention, described step (1) is: the component that accurately takes following weight portion:
The application of the anistree alcohol of a kind of Flos Caryophylli in preparation control hepatic fibrosis medicines.
In a preferred embodiment of the invention, the application dose of the anistree alcohol of Flos Caryophylli is 5~50mg/70kg body weight every day.
Further preferred, the application dose of the anistree alcohol of Flos Caryophylli is 5~40mg/70kg body weight every day.
The invention has the beneficial effects as follows:
1, the anistree alcohol wide material sources of the main effective ingredient Flos Caryophylli of control hepatic fibrosis medicines of the present invention, can from natural materials, directly extract and be isolated, and extract the easy and simple to handle of separation, therefore have the control hepatic fibrosis medicines of its production to have the advantages that cost is low;
2, the anistree alcohol of the main effective ingredient Flos Caryophylli of control hepatic fibrosis medicines of the present invention is as a kind of natural drug, and its time of using as conventional medicament is remote, and the anistree alcohol of Flos Caryophylli is safe as drug use;
3, control hepatic fibrosis medicines of the present invention has good control hepatic fibrosis effect, thereby can be using the anistree alcohol of Flos Caryophylli as control hepatic fibrosis material or relevant lead compound and for pharmaceutical manufacturing, and then the source of having widened control hepatic fibrosis natural drug.
Accompanying drawing explanation
Fig. 1 is the result statistics block diagram of the anistree alcohol of Flos Caryophylli to tetrachloro-methane induction acute hepatic injury mice serum glutamic pyruvic transminase (ALT) in the embodiment of the present invention 3, " ## " represents P<0.01, compared significant difference with blank group (Control); " * " represents P<0.05; " * * " represents P<0.01, compared significant difference with model control group (Model);
Fig. 2 is the result statistics block diagram of the anistree alcohol of Flos Caryophylli to tetrachloro-methane induction acute hepatic injury mice serum glutamic oxalacetic transaminase (AST) in the embodiment of the present invention 3, " ## " represents P<0.01, compared significant difference with blank group (Control); " * " represents P<0.05; " * * " represents P<0.01, compared significant difference with model control group (Model);
Fig. 3 is the result statistics block diagram of the anistree alcohol of Flos Caryophylli to tetrachloro-methane induction acute hepatic injury mice serum alkaline phosphatase (ALP) in the embodiment of the present invention 3, " ## " represents P<0.01, compared significant difference with blank group (Control); " * " represents P<0.05; " * * " represents P<0.01, compared significant difference with model control group (Model);
Fig. 4 is the result statistics block diagram of the anistree alcohol of Flos Caryophylli to tetrachloro-methane induction acute hepatic injury mice Liver Superoxide Dismutase Activity (SOD) in the embodiment of the present invention 3, " ## " represents P<0.01, compared significant difference with blank group (Control); " * " represents P<0.05; " * * " represents P<0.01, compared significant difference with model control group (Model);
Fig. 5 is the result statistics block diagram of the anistree alcohol of Flos Caryophylli to tetrachloro-methane induction acute hepatic injury mice liver malonaldehyde (MDA) in the embodiment of the present invention 3, " ## " represents P<0.01, compared significant difference with blank group (Control); " * " represents P<0.05; " * * " represents P<0.01, compared significant difference with model control group (Model).
The specific embodiment
By the specific embodiment, by reference to the accompanying drawings technical scheme of the present invention is further detailed and is described below.
Embodiment 1
A control hepatic fibrosis medicines, comprises the anistree alcohol of main effective ingredient Flos Caryophylli, and its application dose is calculated as 5~50mg/70kg body weight every day with the anistree alcohol of Flos Caryophylli, preferred, with the anistree alcohol of Flos Caryophylli, is calculated as 5~40mg/70kg body weight every day.This medicine also can comprise one or more in filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, solvent, surfactant, flavouring agent, antiseptic, lubricant, sweeting agent and pigment.This control hepatic fibrosis medicines is tablet, capsule, granule or syrup.
A preparation method for above-mentioned control hepatic fibrosis medicines, this medicine is tablet, comprises the steps:
(1) accurately take the component of following weight portion:
Preferred:
(2) by the anistree alcohol of above-mentioned Flos Caryophylli, microcrystalline Cellulose, stearic acid, lactose and micropowder silica gel mix homogeneously, granulation;
(3) in above-mentioned granule, add above-mentioned magnesium stearate, mix rear tabletting, obtain described control hepatic fibrosis medicines.
In the test of the following example 2 to 5, in the result statistics block diagram that each model control group is drawn in corresponding experimental result, abscissa all adopts Model mark, and each blank group abscissa in the result statistics block diagram that experimental result is drawn accordingly all adopts Control mark.
Embodiment 2 alcohol extraction chromatographys extract the anistree alcohol of separated Flos Caryophylli
The Flos Carthami of 3.5kg anistree (Illicium dunnianum Tutch) is ground into powder; Take 95% ethanol as extracting solvent, and 60 ℃ of reflux, extract, 2 hours, reclaim solvent and obtain its ethanol extraction; Use afterwards petroleum ether dissolution gained ethanol extraction, and adopt silica gel column chromatography separated, and with petroleum ether-ethyl acetate system gradient elution, co-elute goes out 16 components; (the chloroform: methanol=7:3) (methanol: water=3:7) column chromatography is purified can obtain the anistree alcohol (374mg) of Flos Caryophylli for column chromatography and ODS of the 16th Sephadex LH-20 for component after eluting.
The anistree alcohol of embodiment 3 Flos Caryophylli causes the protective effect of chmice acute chemical liver injury to carbon tetrachloride
(1) laboratory animal: male ICR mouse is bought from Fujian university of TCM Experimental Animal Center, body weight 22-26g, credit number is SCXK (Fujian) 2010-0001; Animal is placed in the cage of 320 * 180 * 160cm, 8, every cage, and mice conforms one week; In whole experimentation, give the mice feed of freely intaking, ambient temperature is 22 ± 2 ℃, and relative humidity is 55 ± 5%, illumination every day 12 hours (morning 7 to point in evenings 7).
(2) medicine configuration: positive drug bifendate (BIF) is configured to the medicinal liquid of 100mg/10ml; The anistree alcohol of Flos Caryophylli is configured to three dosage medicinal liquids of 10mg/ml, 20mg/ml, 40mg/ml.
(3) animal grouping and administering mode: 60 of mices, be divided into 6 groups, every group 10, be respectively Normal group (normal saline), dosage group (40mg/kg), the anistree alcohol high dose group (80mg/kg) of Flos Caryophylli in model control group (normal saline), positive drug bifendate group (100mg/kg), the anistree alcohol low dose group (20mg/kg) of Flos Caryophylli, the anistree alcohol of Flos Caryophylli; Press Mouse Weight 10ml/kg gastric infusion, be administered once, tail test is hanged in administration after 1 hour.
(4) experimental technique: the corresponding medicine of gavage every day 1 time, continuous 7 days, with 2h after last administration, Normal group lumbar injection 10mg/kg olive oil, all the other 5 groups equal lumbar injection 0.1% carbon tetrachloride 10mg/kg, after fasting 16h, from mice clump posterior orbit venous blood sampling, adopt conventional kit method to measure glutamate pyruvate transaminase (ALT), glutamic oxaloacetic transaminase, GOT (AST), alkali phosphatase (ALP) activity in mice serum; And the level of liver superoxide dismutase (SOD) and hepatic tissue malonaldehyde (MDA).
(5) statistical method: experimental result adopts one factor analysis of variance in conjunction with Dunnett ' s postmortem analysis; With P value, be less than 0.05 expression significant difference significance.
(6) experimental result refers to Fig. 1 to Fig. 5, one factor analysis of variance, and significantly raise in mice serum ALT, AST and ALP of carbon tetrachloride is active, reduces the content of liver SOD activity and rising liver MDA.Dunnett ' s postmortem analysis shows, the anistree basic, normal, high dosage group of alcohol of Flos Caryophylli and positive drug bifendate group all can significantly reduce carbon tetrachloride and cause the too high ALT of acute chemical hepatic injury mice serum, AST, ALT activity, rising liver SOD is active, and reduces liver MDA content.
The above, be only preferred embodiment of the present invention, therefore can not limit according to this scope of the invention process, the equivalence done according to the scope of the claims of the present invention and description changes and modifies, and all should still belong in the scope that the present invention contains.

Claims (9)

1. a control hepatic fibrosis medicines, is characterized in that: comprise the anistree alcohol of main effective ingredient Flos Caryophylli, its application dose is calculated as 5~50mg/70kg body weight every day with the anistree alcohol of Flos Caryophylli.
2. a kind of control hepatic fibrosis medicines as claimed in claim 1, is characterized in that: its application dose is calculated as 5~40mg/70kg body weight every day with the anistree alcohol of Flos Caryophylli.
3. a kind of control hepatic fibrosis medicines as claimed in claim 1, is characterized in that: also comprise one or more in filler, binding agent, wetting agent, disintegrating agent, absorption enhancer, solvent, surfactant, flavouring agent, antiseptic, lubricant, sweeting agent and pigment.
4. a kind of control hepatic fibrosis medicines as claimed in claim 1, is characterized in that: this control hepatic fibrosis medicines is tablet, capsule, granule or syrup.
5. a preparation method of preventing and treating hepatic fibrosis medicines, is characterized in that: this medicine is tablet, comprises the steps:
(1) accurately take the component of following weight portion:
(2) by the anistree alcohol of above-mentioned Flos Caryophylli, microcrystalline Cellulose, stearic acid, lactose and micropowder silica gel mix homogeneously, granulation;
(3) in above-mentioned granule, add above-mentioned magnesium stearate, mix rear tabletting, obtain described control hepatic fibrosis medicines.
6. a kind of preparation method of preventing and treating hepatic fibrosis medicines as claimed in claim 1, is characterized in that:
Described step (1) is: the component that accurately takes following weight portion:
7. the anistree alcohol of Flos Caryophylli is prevented and treated the application in hepatic fibrosis medicines in preparation.
8. application as claimed in claim 7, is characterized in that: the application dose of the anistree alcohol of Flos Caryophylli is 5~50mg/70kg body weight every day.
9. application as claimed in claim 8, is characterized in that: the application dose of the anistree alcohol of Flos Caryophylli is 5~40mg/70kg body weight every day.
CN201410322989.8A 2014-07-08 2014-07-08 A kind of preventing and treating hepatic fibrosis medicines and preparation method thereof Expired - Fee Related CN104095832B (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107050004A (en) * 2017-04-20 2017-08-18 郑州大学 Application of the triphenyl Ne olignan in anti-vancocin resistance enterococcus
CN108938638A (en) * 2018-06-25 2018-12-07 天津医科大学 ZINC62678696 inhibits the purposes of hepatic fibrosis medicines in preparation

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103083287A (en) * 2013-01-11 2013-05-08 华侨大学 Application of iIllicium macranthum alcohol in preparation of medicine for treating depression

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103083287A (en) * 2013-01-11 2013-05-08 华侨大学 Application of iIllicium macranthum alcohol in preparation of medicine for treating depression

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107050004A (en) * 2017-04-20 2017-08-18 郑州大学 Application of the triphenyl Ne olignan in anti-vancocin resistance enterococcus
CN108938638A (en) * 2018-06-25 2018-12-07 天津医科大学 ZINC62678696 inhibits the purposes of hepatic fibrosis medicines in preparation
CN108938638B (en) * 2018-06-25 2021-06-08 天津医科大学 Application of ZINC62678696 in preparation of medicine for inhibiting hepatic fibrosis

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