CN1887303A - Application of alcohol extract of spanishneedles herb in preparing medicine for preventing and treating non-alcoholic fatty liver - Google Patents

Application of alcohol extract of spanishneedles herb in preparing medicine for preventing and treating non-alcoholic fatty liver Download PDF

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CN1887303A
CN1887303A CNA200510097344XA CN200510097344A CN1887303A CN 1887303 A CN1887303 A CN 1887303A CN A200510097344X A CNA200510097344X A CN A200510097344XA CN 200510097344 A CN200510097344 A CN 200510097344A CN 1887303 A CN1887303 A CN 1887303A
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alcohol extract
fatty liver
herb
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alcoholic fatty
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CN100486601C (en
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陈飞虎
李俊
袁凤来
金涌
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Anhui Medical University
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Anhui Medical University
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Abstract

The present invention relates to the use of alcohol extract of sponish needles herb in preparing medicine for preventing and treating non-alcoholic fatty liver. The alcohol extract of sponish needles herb is the effective part extracted from sponish needles herb, and animal experiments show that alcohol extract of sponish needles herb can lower the lipid of high fat diet resulted in model animal and drug poisoning model animal and protect liver cell of the fatty liver animal. The medicine of alcohol extract of sponish needles herb for preventing and treating non-alcoholic fatty liver is orally taken, and has taking convenience and less toxic side effect.

Description

The application of alcohol extract of spanishneedles herb in preparation control non-alcoholic fatty liver disease medicine
Technical field
The present invention relates to the new purposes of alcohol extract of spanishneedles herb, relate in particular to the purposes of alcohol extract of spanishneedles herb in pharmaceutical field, the definite purposes of saying so and preventing and treating in the non-alcoholic fatty liver disease medicine preparing.
Background technology
Herba Bidentis Bipinnatae has another name called Herba Bidentis Bipinnatae, terrible wooden fork grass, little Bidens bipinnata, sticking body grass etc., and its medicinal history is long, and the beginning is stated from Tang's CHEN Zang-Qi supplement to the Herbal, meaning: " terrible hairpin grass, bitter in the mouth is flat, nontoxic, main Serpentis and Aranea sting, broken Fu of pestle it, also pestle strand juice clothes.There is fork at Radix Rehmanniae side, and square-stem, son are made the hairpin foot, people such as clothing pin, and what exhaled in the north is Bidens bipinnata.But " all medications of Herba Bidentis Bipinnatae class medical material herb, bitter in the mouth is flat and nontoxic, has heat-clearing and toxic substances removing, and effects such as dissipating blood stasis for subsidence of swelling cure mainly malaria, diarrhoea, dysentery, hepatitis, acute nephritis, stomachache, dysphagic, acute appendicitis, laryngopharynx swelling and pain, traumatic injury, snake bite and insect sting etc.In order better to be familiar with and to understand this natural resources, better develop and use, existing that the research and development review of Present Situation of Herba Bidentis Bipinnatae is as follows.
Herba Bidentis Bipinnatae is that Compositae (Compositae) tubular flower subfamily Bidens (Bidens L.) plant is an annual herb, its herb resource is very abundant, mainly be distributed in ground such as China northeast, Hebei, Shandong, Shanxi, Henan, Jiangsu, Yunnan, Sichuan, Guangdong and Guangxi Provinces, be born in waterside, riverbank, wetland, wasteland and hillside etc. and locate, very easily gather.
The chemical constituent of Herba Bidentis Bipinnatae:
The contained chemical constituent kind of Herba Bidentis Bipinnatae is more, and bibliographical information once separated from this plant and obtains volatile oil, sterol, chalcone derivative, aurones, polyacetylene class etc., and its active component is based on polyacetylene class and flavones ingredient.Isolated multiple polyacetylene constituents.The n-butyl alcohol of ethanol extraction partly identifies 4 flavone components, is hyperin (hyperoside), okanin (okanin), isookanin-7-O-glycoside and maritimetin (maritimein).In each position of Herba Bidentis Bipinnatae there be than big-difference flavones ingredient, at flowering fruit bearing stage, and general flavone content higher (being respectively 6.67% and 6.68%) in leaf and the inflorescence, content lower (0.89%) in the stem branch.In the leaf isolation identification 21 kinds of volatile ingredients, be mainly fatty alkane and fatty acid, contain a spot of aldehyde, ketone alkene, nitrile, amine and furans composition in addition; Wherein fats compound accounts for significant proportion.Isolated 4 kinds of liposoluble ingredients through physics and chemistry test and spectrum analysis, are accredited as salicylic acid, protocatechuic acid, gallic acid, fatty acid compound respectively.Also have steroid compound such as spinach sterol, daucosterol, sitosterol, stigmasterol-3-O-β-D-glucoside.
Herba Bidentis Bipinnatae contains rich in amino acid, as 17 seed amino acids such as aspartic acid, threonine, serine, glutamic acid, alanine, valine, isoleucine, proline, tyrosine, lysines, wherein 8 kinds is essential amino acid, gross protein 157.89g/kg, total free amino acid content reaches 139.89g/kg, TEAA 57.09g/kg.Amino acid contained and the traditional rare medicinal herbs Cordyceps hawkesii Gary of Herba Bidentis Bipinnatae, Cordyceps are compared, many cystine on kind, and proline, glutamic acid are higher than both on content, and other amino acid contents are suitable
Also contain 11 kinds of micro elements needed by human in addition in the Herba Bidentis Bipinnatae, measurement result shows, Mg content is the highest, P, Fe, Ca content are higher, Cu, Zn take second place, Mn, Co, Ni, Mo, Cr content are minimum, contain abundant P in the Herba Bidentis Bipinnatae, are that it regulates immanent cause that nerve, hypnosis, calmness etc. act on.
Vitamin also has distribution in Herba Bidentis Bipinnatae, as vitamin B 1, vitamin B 2, beta-carotene.
The Herba Bidentis Bipinnatae herb resource is abundant, and medicinal history is long, and Radix Codonopsis Cardiophyllae's title is arranged in folk remedy.Its biological activity is various, and action temperature and lasting, has higher medical value, especially digestive system, central nervous system and cardiovascular system is shown stronger pharmacological action.In recent years the Herba Bidentis Bipinnatae medical material some developments and utilizations have been carried out, domestic Herba Bidentis Bipinnatae product has the year of a pleasing sheet, Herba Bidentis Bipinnatae oral liquid, Herba Bidentis Bipinnatae health instant powder etc. at present, but also only limit to prevent and treat cardiovascular disease such as hypertension, yet there are no alcohol extract of spanishneedles herb at the report aspect the preparation control non-alcoholic fatty liver disease medicine.
Summary of the invention
The new purposes that the purpose of this invention is to provide alcohol extract of spanishneedles herb, i.e. new application in pharmacy.
In fact, the invention provides the application of alcohol extract of spanishneedles herb in the medicine of preparation prevention or treatment non-alcoholic fatty liver disease.
In recent years, along with improving constantly of China people material life, the sickness rate of non-alcoholic fatty liver disease (NASH) rises year by year, surpasses viral hepatitis and becomes first hepatopathy at certain areas non-alcoholic fatty liver disease NASH.Non-alcoholic fatty liver disease NASH is that the class liver histological similar to alcoholic liver disease changes, but not having excessive history of drinking history (takes in the clinical pathology syndrome of ethanol＜40g/d), is primary in metabolism disorders such as the obesity relevant with insulin resistant, type ii diabetes, hyperlipemia, hypertension usually.Previously think, fatty liver is a benign lesion, can not develop into hepatic fibrosis, liver cirrhosis, but a large amount of clinical liver biopsies studies confirm that, non-alcoholic fatty liver disease NASH about 40%-50% on the basis of fat hepatitis can develop into hepatic fibrosis, 15%-20% can develop into liver cirrhosis, even can cause the generation of hepatocarcinoma.Therefore the positive control of NASH can stop the progress of chronic hepatopathy, improves NASH patient's prognosis.
The measure that is used for the treatment of at present non-alcoholic fatty liver disease NASH clinically mainly comprises (1) removal cause of disease and inducement; (2) keep on a diet; (3) exercise therapy; (4) pharmaceutical intervention etc.The drug development for the treatment of NASH in recent years is very fast, and its main medicine has:
A, at improving insulin resistant, increase the medicine of insulin sensitivity.As the two croaks of diformazan, can obviously improve patient's carbohydrate tolerance and hyperinsulinemia, reduce blood plasma free fatty acid and plasma triglyceride level.Its main adverse reaction is a symptom of digestive tract, has the inclination, the gerontal patient of renal dysfunction has the danger that lactic acidosis takes place, and does not still have the randomized controlled experimentation at present and confirms that this medicine can be used safely in to treat non-alcoholic fatty liver disease.
B, inhibition peroxidation medicine.As vitamins, main prevent that by suppressing the formation of peroxylradicals cell is impaired, but vitamin A, E all belong to fatsoluble vitamin, heavy dose of replenishing easily produces accumulate poisoning and increases the weight of hepatic injury.
C, at the medicine of hyperlipemia, carry out metabolism but many hypolipidemics can promote blood fat more to concentrate on liver, may promote lipid accumulating in liver on the contrary, and further damage liver function.
D, ursodesoxycholic acid can reduce non-alcoholic fatty liver disease patients serum enzyme level, but can not change the liver fat deposition.
Generally speaking, though the medicine of large quantities of treatment non-alcoholic fatty liver diseases is arranged at present, still lack the medicine safe and effective, that effect is sure for clinical use.Therefore, actively seek have protect the liver, blood fat reducing, lipotropic medicine be very important, and the advantage of performance Chinese medicine is particularly important.The great advantage of the chronic fatty liver illness of Chinese medicine is that side effect is little, and in treatment, its disease that is associated is had certain therapeutical effect as obesity, hyperlipemia, hypertension, diabetes etc., so have wide application and DEVELOPMENT PROSPECT.
According to Traditional Chinese medical theory, the differential diagnosis in tcm of most of chronic hepatitis patients diagnosis pattern of syndrome is syndrome of stagnation of liver qi and spleen deficiency and congestion resistance network card, and corresponding treatment should be benefiting QI and nourishing blood, blood circulation promoting and blood stasis dispelling, the liver soothing and the spleen invigorating.The present invention follows this Therapeutic Principle, based on the long-term treatment experience, find that Herba Bidentis Bipinnatae has heat-clearing and toxic substances removing, effects such as dissipating blood stasis for subsidence of swelling, not only have effects such as resisting hypertension, blood sugar lowering, and non-alcoholic fatty liver disease also had good therapeutical effect, for the active drug that it is developed to the hepatopathy effect provides the foundation that is of great rarity.We extract its effective site, confirm the effect that it has significant control non-alcoholic fatty liver disease by zoopery.
In order to understand essence of the present invention better, will its application in control non-alcoholic fatty liver disease medicine be described with the pharmacological evaluation and the result of alcohol extract of spanishneedles herb below.
The test of alcohol extract of spanishneedles herb control non-alcoholic fatty liver disease is as follows:
(1) preparation of alcohol extract of spanishneedles herb
Get the Herba Bidentis Bipinnatae crude drug and pulverize, the alcohol reflux of 40-80% 2-3 time, extracting solution merges, and reclaims ethanol, and concentrating under reduced pressure gets extractum.Extractum is water-soluble, leaves standstill, filter, and resin column on the clear liquor, 40-95% ethanol elution part is collected in the washing back, reclaims ethanol, and concentrating under reduced pressure is drying to obtain alcohol extract of spanishneedles herb.This alcohol extract is the yellow green powder, has fragranced, easily deliquescence; Its main component is a total flavones, and content is 20-60%.This alcohol extract can add corresponding adjuvant, makes tablet, capsule, slow releasing tablet, drop pill, electuary, microgranule, and is further purified and makes injection.
(2) experiment
1. alcohol extract of spanishneedles herb causes the protective effect of chmice acute chemical liver injury to carbon tetrachloride
(1) material and reagent: alcohol extract of spanishneedles herb; 0.1%CCl 4Bifendate; ALT, the AST test kit: biotech company is built up in Nanjing; 60 of Male Kunming strain mice, body weight 18-22g is provided by Medical University Of Anhui zoopery center.
(2) method: 60 of normal mouses divide 6 groups at random, gastric infusion (alcohol extract of spanishneedles herb 80mg/kg, 160mg/kg, 320mg/kg, positive drug control group bifendate 100mg/kg) or equal-volume normal saline (normal control, model), every day 2 times, continuous 7d, 2h after the last administration, normal control group ip10ml/kg Oleum Arachidis hypogaeae semen, all the other 5 groups of equal ip0.1%CCl 410ml/kg from mice posterior orbit vein treating the preponderant disease instead of the secondary disease blood, measures Serum ALT behind the fasting 16h, the AST activity, and get the same position of liver lobus sinister, fixing, do pathological section, carry out hepatic pathology histology HE chromoscopy, the result with hepatic pathology degree of injury scoring under the light microscopic and pathology photo as standard.
Liver tissue lesions's grading method: light microscopic is checked down, is divided into 5 grades by the hepatic necrosis degree:
0 grade, normal or liver has slight degeneration, and hepatocyte does not have necrosis;
The I level, spotty necrosis, necrosis accounts for lobules of liver＜1/4;
The II level, the necrosis of some kitchen range shape, necrosis accounts for lobules of liver 1/4-1/3;
The III level, the necrosis of kitchen range shape, necrosis accounts for lobules of liver＜1/2;
The IV level, lamellar necrosis, necrosis account for lobules of liver＞1/2
(3) result: table 1 is the result show, CCl 4ALT, AST activity in the remarkable rising mice serum, and alcohol extract of spanishneedles herb significantly reduces CCl 4Cause ALT too high in the acute chemical hepatic injury mice serum, AST activity.
Table 1 Sticktight general flavone is to the influence of ALT, AST in the mice serum (n=10, x ± s)
Group Dosage/mgkg -1 ALT/U·L -1 AST/U·L -1
Matched group model group positive drug alcohol extract of spanishneedles herb - - 100 320 160 80 46.13±6.76 144.73±12.11** 46.61±12.51## 57.80±30.22## 75.96±32.58## 105.72±30.00## 45.21±16.12 93.24±36.11** 62.05±14.09 54.79±14.82## 37.96±14.10## 79.85±26.75
* p＜0.01 is compared with matched group; ##p＜0.01 is compared with model group
Table 2 result shows that necrosis in different degree appears in the visible inflammatory cell infiltration of model group hepatic tissue.Alcohol extract of spanishneedles herb can obviously alleviate liver inflammatory cell infiltration and necrosis.
Table 2 alcohol extract of spanishneedles herb is to CCl 4Cause the influence of acute chemical hepatic injury mice histopathology
Group Dosage mg/kg Classification
0 I II III IV
Normal group - 10 0 0 0 0
Model group - 3 4 2 2 0
The positive drug group 100 11 0 0 0 0
Alcohol extract of spanishneedles herb 320 10 2 0 0 0
160 12 0 0 0 0
80 0 2 3 3 4
1, alcohol extract of spanishneedles herb is to the therapeutical effect of serum lipids in rats fatty liver
(1) material and reagent:
66 of SD rats, male and female half and half, body weight 180-200g is provided by Medical University Of Anhui's Experimental Animal Center; Alcohol extract of spanishneedles herb; DONGBAO GANTAI PIAN (Shanghai nine good fortune pharmaceutcal corporation, Ltds); TG, TC, HDL-C measure test kit available from Beijing Fu Rui bio-engineering corporation; ALT, MDA, SOD, GLU, FFA measure test kit and build up bio-engineering research institute available from Nanjing;
The preparation of lipomul: get in the beaker that Adeps Sus domestica 25g adds 200mL, heated and stirred adds the 10g cholesterol, dissolves, and it is excellent to add 1g third match again, fully stirs evenly, and adds the 25mL Tween 80 then, makes oil phase.Add 30mL distilled water and 1-2 propylene glycol 20mL simultaneously in another beaker, heating adds the 2g NaTDC then, fully stirs up to dissolving fully, makes water.Then water is added oil phase, fully mixing is promptly made lipomul, uses preceding 37 ℃ of heating in water bath.
(2) method:
The SD rat after one week, is divided into 2 groups at laboratory rearing at random: normal group (n=12), lipomul group (n=54).The lipomul group gives lipomul filling stomach every day, and normal group gives equal-volume CMC-Na simultaneously.Behind the 3W, hematometry TG is got in docking, the lipomul group get 50 by blood lipid level be divided into DONGBAO GANTAI group, alcohol extract of spanishneedles herb (320,160,80mgkg -1) group, model group, to remove matched group and model group and give equal-volume CMC-Na, other each group gives relative medicine respectively.3 week of administration, animal was put to death in the back, and taking-up serum and liver are measured serum TG, TC, HDL-C, ALT, MDA, SOD, FFA and liver homogenate TG, MDA, SOD.
(3) result
Make when touching for 3 weeks, lipomul group blood fat significantly raises.Make as seen from Table 3 touch 6 when week the model group serum TC and TG all be significantly higher than matched group; Compare with model group, DONGBAO GANTAI group and Sticktight general flavone group serum TG obviously reduce, and Serum HDL-C raises.As seen, compare with matched group in the variation of table 4 Serum ALT, SOD, MDA, FFA, model group ALT, FFA, MDA obviously raise; Compare with model group, east protects the liver safe group and alcohol extract of spanishneedles herb group FFA, MDA, ALT obviously descend.Compare with matched group in the visible liver homogenate of table 5, model group TG, MDA significantly raise, and SOD then reduces; Compare with model group, DONGBAO GANTAI group and alcohol extract of spanishneedles herb group can reduce TG, MDA, and the alcohol extract of spanishneedles herb group can also increased SOD.Show that thus alcohol extract of spanishneedles herb has the effect of tangible Chinese People's Anti-Japanese Military and Political College Mus hyperlipemia-fatty liver.
Table 3 the 6th respectively organize during week serum lipids change (x ± s, n=10)
Group Dosage/mgkg -1 TG/mmol·l -1 TC/mmol·l -1 HDL-C/mmol·l -1
Matched group model group DONGBAO GANTAI alcohol extract of spanishneedles herb - - 120 320 160 80 0.39±0.09 0.54±0.10** 0.47±0.08# 0.43±0.08# 0.46±0.10# 0.54±0.10 1.45±0.17 2.14±0.28** 2.23±0.50 2.13±0.36 2.25±0.30 2.26±0.43 1.05±1.45## 0.53±0.1 0.67±0.06# 0.66±0.10# 0.65±0.06# 0.64±0.08#
* p＜0.05, * * p＜0.01 is compared with matched group; #p＜0.05, ##p＜0.01 is compared with model group
Table 4 respectively organize Serum ALT, MDA, SOD, FFA variation (x ± s, n=10)
Group Dosage/mgkg -1 FFA/μmol·ml -1 ALT/U·l -1 MDA/n mol·ml -1 S0D/U·ml -1
The alcohol extraction of matched group model group DONGBAO GANTAI Herba Bidentis Bipinnatae - - 120 320 160 80 430.69±134.92 758.58±103.54** 565.23±99.96## 504.64±108.64## 616.65±128.05# 744.85±108.96 13.62±8.40 44.95±21.10** 24.57±15.28# 23.81±13.28# 24.61±8.99# 34.90±16.68 15.52±2.02 18.69±3.37* 16.12±1.67# 15.23±2.61# 16.05±2.41# 18.26±3.51 189.09±23.72 172.80±24.19 190.22±17.85 191.34±18.80 180.67±19.58 178.31±17.54
* p＜0.05, * * p＜0.01 is compared with matched group; #p＜0.05, ##p＜0.01 is compared with model group
Table 5 respectively organize TG in the liver homogenate, MDA, SOD variation (x ± s, n=10)
Group Dosage/mgkg -1 TG mmol·l -1 MDAnmol·mg - SODU·mg -1
Matched group model group DONGBAO GANTAI alcohol extract of spanishneedles herb - - 120 320 160 80 0.47±0.07 1.04±0.12** 0.72±0.10## 0.62±0.11## 0.90±0.08## 0.93±0.12# 0.25±0.07 0.42±0.07** 0.34±0.10# 0.32±0.09## 0.34±0.09# 0.33±0.08# 7.57±1.02 6.46±0.71* 7.12±0.76 7.41±1.21# 7.27±1.59 6.30±0.66
* p＜0.05, * * p＜0.01 is compared with matched group; #p＜0.05, ##p＜0.01 is compared with model group
2, alcohol extract of spanishneedles herb causes the influence of rat fat liver to ethionine
(1) method: get 66 of SD rats, male and female half and half, body weight is 180-200g, is divided into 6 groups, promptly blank group and model group (irritate stomach give equal-volume CMC-Na), DONGBAO GANTAI group, alcohol extract of spanishneedles herb (320,160,80mgkg -1).From testing the 1st day, every day gastric infusion once, successive administration 3 days is tested and was risen in the 4th day, except that the blank group, irritates stomach by the 0.25g/kg body weight respectively for all the other 5 groups and gives ethionine once, subsequently, every 12h is administered once by preceding method, totally 4 times.Give 48h behind the ethionine, get hematometry TC, TG and liver homogenate TC, TG.
(2) result:
Table 6 alcohol extract of spanishneedles herb causes the influence (x ± s) of rat fat liver to ethionine
Group Dosage/mgkg -1 Blood TCmmol/l Blood TGmmol/l Liver TCmmol/l Liver TGmmol/l
Matched group model group DONGBAO GANTAI Sticktight general flavone - - 120 320 160 80 0.64±0.12** 0.91±0.16 0.58±0.11** 0.59±0.15** 0.61±0.12** 0.63±0.11** 0.63±0.11* 0.83±0.21 0.60±0.12* 0.62±0.13* 0.64±0.14* 0.75±0.12 0.50±0.13** 0.67±0.09 0.46±0.16** 0.42±0.08** 0.48±0.09** 0.53±0.12* 0.44±0.09** 0.65±0.12 0.48±0.13* 0.44±0.131** 0.47±0.15* 0.49±0.16*
* p＜0.05, * * p＜0.01 is compared with model group
By the visible alcohol extract of spanishneedles herb of table 6 result obviously hypercholesterolemia reducing and content of triglyceride, has the effect that certain anti-ethionine causes fatty liver.
Above-mentioned experimental result shows that the present invention has the advantage of several aspects:
1, alcohol extract of spanishneedles herb of the present invention is the effective ingredient that extracts from the Chinese crude drug Herba Bidentis Bipinnatae, can obviously reduce the lipid in high fat diet fatty liver model and the drug intoxication fatty liver model, and the hepatocyte in the fatty liver model is had protective effect; Excavate the new prospect in medicine of alcohol extract of spanishneedles herb, opened up a new medicinal field;
2, alcohol extract of spanishneedles herb of the present invention adopts oral administration, taking convenience, and toxic and side effects is little, takes medicine for a long time and does not have harm;
3, the former medicine resource of alcohol extract of spanishneedles herb of the present invention is very abundant, has good society and economic benefit;
4, alcohol extract of spanishneedles herb of the present invention is applicable to non-alcoholic fatty liver disease, acts on a plurality of links, determined curative effect;
5, the present invention provides strong basis for Herba Bidentis Bipinnatae being developed further into new drug.
The specific embodiment
Below in conjunction with embodiment the present invention is done to describe further.
Embodiment 1:
Take by weighing Herba Bidentis Bipinnatae crude drug 10kg, pulverize the back and add 80% ethanol 100L, hot reflux is extracted 2 times, each 1h, and merge extractive liquid, reclaims ethanol, and concentrating under reduced pressure gets extractum.Extractum is water-soluble, leaves standstill, filter, and macroporous resin column on the clear liquor, 80% ethanol elution part is collected in the washing back.Reclaim ethanol, concentrating under reduced pressure is drying to obtain alcohol extract of spanishneedles herb.This alcohol extract is the yellow green powder, has fragranced, easily deliquescence; Its main component is a total flavones, and content is 20-60%.This alcohol extract can add corresponding adjuvant, makes tablet, capsule, slow releasing tablet, drop pill, electuary, microgranule, and is further purified and makes injection.
The clinical recommended dose of alcohol extract of spanishneedles herb: 300-1200mg/ days, oral, three times on the one.

Claims (1)

1, the application of alcohol extract of spanishneedles herb in preparation control non-alcoholic fatty liver disease medicine is characterized in that: the application of alcohol extract of spanishneedles herb in preparation control non-alcoholic fatty liver disease medicine.
CN 200510097344 2005-12-31 2005-12-31 Application of alcohol extract of spanishneedles herb in preparing medicine for preventing and treating non-alcoholic fatty liver Expired - Fee Related CN100486601C (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103416352A (en) * 2012-05-22 2013-12-04 浙江中医药大学 Animal model of hypertension comprehensively caused by high-salt, high-sugar and high-fat diet
CN103416347A (en) * 2012-05-22 2013-12-04 浙江中医药大学 Lifestyle hypertension animal model caused by drinking and high-sugar high-fat diet

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103416352A (en) * 2012-05-22 2013-12-04 浙江中医药大学 Animal model of hypertension comprehensively caused by high-salt, high-sugar and high-fat diet
CN103416347A (en) * 2012-05-22 2013-12-04 浙江中医药大学 Lifestyle hypertension animal model caused by drinking and high-sugar high-fat diet

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