CN103655544B - The application of Jaceosidin in preparation prevention or the Fibrotic medicine for the treatment of chronic hepatic injury regulating liver-QI - Google Patents
The application of Jaceosidin in preparation prevention or the Fibrotic medicine for the treatment of chronic hepatic injury regulating liver-QI Download PDFInfo
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- YFZSQPRYLBGYKE-UHFFFAOYSA-N Jaceoside Natural products C1=C(O)C(OC)=CC(C=2OC3=CC(OC4C(C(O)C(O)C(CO)O4)O)=C(OC)C(O)=C3C(=O)C=2)=C1 YFZSQPRYLBGYKE-UHFFFAOYSA-N 0.000 title claims abstract description 44
- GLAAQZFBFGEBPS-UHFFFAOYSA-N jaceosidin Chemical compound C1=C(O)C(OC)=CC(C=2OC3=CC(O)=C(OC)C(O)=C3C(=O)C=2)=C1 GLAAQZFBFGEBPS-UHFFFAOYSA-N 0.000 title claims abstract description 44
- AOAPCDXPLWGVGI-UHFFFAOYSA-N jaceosidin Natural products COc1c(O)cc2OC(=CC(=O)c2c1O)c3ccc(O)c(C)c3 AOAPCDXPLWGVGI-UHFFFAOYSA-N 0.000 title claims abstract description 44
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides the new medicine use of Jaceosidin, be specifically related to Jaceosidin and preventing or treating the application in the medicine of chronic hepatic injury and hepatic fibrosis.In above-mentioned application, Jaceosidin using dosage scope is 20mg ~ 1000mg; Preferably 20 ~ 500mg.
Description
Technical field
The medicine in a kind of hepatopathy field of system of the present invention, content relates to Jaceosidin and suppresses the Fibrotic generation development of chronic hepatic injury regulating liver-QI thus prevent or treat chronic hepatic injury and hepatic fibrosis.
Background technology:
Viral hepatitis in recent years, hepatic fibrosis, fatty liver, alcoholic liver, medicamentous liver lesion and liver cirrhosis, the hepatopathys such as hepatocarcinoma are that society threatens one of principal disease of human health.China is hepatopathy big country, has more than 14% population to infect according to recent statistics viral hepatitis and hepatitis B virus carriers in the middle of population of China.Aggravation then develops into hepatic fibrosis, hepatic ascites, liver abdomen and hepatocarcinoma.Die from liver cirrhosis every year, the patient of hepatocarcinoma just has more than 100 ten thousand.
Hepatic fibrosis is the common pathologic basis of various chronic hepatopathy, is the important stage of liver cirrhosis generating process, is often caused by reasons such as chronic inflammatory disease, cholestasis, immunologic injuries in liver.The sickness rate having data to show hepatic fibrosis is 85.1%, and hepatic fibrosis sustainable development will have 25%-40% to develop into liver cirrhosis.Research confirms that hepatic fibrosis is reversibility pathological changes, so development suppresses the Fibrotic medicine of chronic hepatic injury regulating liver-QI highly significant.
Folium Artemisiae Argyi (FoliumArtemisiaeArgyi) derives from the dried leaves of Compositae sagebruss Chinese mugwort (ArtemisiaargyiLevl.etVant.), is clinical conventional Chinese medicine.Jaceosidin is from Folium Artemisiae Argyi, extract the single compound [Tang Shengan obtained, Sun Liang, Zhai Huiyuan, Duan Hongquan, Zhang Yanwen. the research of Folium Artemisiae Argyi chemical composition. Medical University Of Tianjin's journal, 2011,17 (4): 461-463.], Jaceosidin has antiinflammatory action [ClavinM, GorzalczanyS, MachoA
e, FerraroG, AcevedoC, MartinoV.Anti-inflammatoryactivityofflavonoidsfromEupato riumamottianum.JEthnopharmaco1.2007; , but Jaceosidin has no report in preparation prevention or treatment chronic hepatic injury regulating liver-QI Fibrotic pharmacological action 112 (3): 585-589.].By large quantifier elimination, the present inventor finds that Jaceosidin has obvious effect to chronic hepatic injury and hepatic fibrosis.Based on this, inventor, by a large amount of experimentatioies, confirms the application of Jaceosidin in prevention or treatment acute and chronic liver injury and hepatic fibrosis.
Summary of the invention
The invention provides Jaceosidin preventing or treating the application in the medicine of chronic hepatic injury and hepatic fibrosis.
The invention provides the application of Jaceosidin in prevention or treatment chronic hepatic injury.
The invention provides the application of Jaceosidin in prevention or treatment hepatic fibrosis.
The medicine that invention provides is when for chronic hepatic injury and hepatic fibrosis, and its using dosage scope is 20mg ~ 1000mg; Preferably 20 ~ 500mg.
Present invention also offers the medicine be made up of Jaceosidin and pharmaceutically acceptable carrier or adjuvant, this medicine can be prepared into tablet, capsule with pharmacy conventional method, preferably exists with tablet form.
Detailed description of the invention
Preparation example 1: prepare Jaceosidin
The Folium Artemisiae Argyi of 1kg drying is pulverized, 3 times are extracted with the alcohol heating reflux of 6 times amount 95%, each 6h, filter, merging filtrate, be evaporated to extractum shape, obtain extract, after adding appropriate distilled water suspendible, with extraction into ethyl acetate in the separatory funnel of 10L, collect extract with silica gel column chromatography (silica gel 600g, 300-400 order) be separated, use CH2C12 → CH2C12:EtoAc (5:1 → 2:1) → EtoAc → MeOH gradient elution successively, merge similar components by TLC, cross silicagel column normal pressure post, obtain Jaceosidin 460mg.
Prepared by embodiment 2 Jaceosidin tablet
Cross 100 mesh sieves after taking 20.0g Jaceosidin, 55.0g Icing Sugar, 100.0g lactose and the abundant mix homogeneously of 23.0g carboxymethyl starch sodium, add appropriate 3%PVP
k30aqueous solution is soft material processed in right amount, and 20 mesh sieves are granulated, and 60 DEG C of dryings 3 hours, 18 mesh sieve granulate, add 2.0g magnesium stearate, and scrobicula punching press after mix homogeneously, adjustment sheet is 200mg heavily about, to obtain final product.
Detailed description of the invention
Test example 1 Jaceosidin is on the impact of rat chronic hepatic injury
1.1 materials and animal
(pharmaceutical college of Binzhou Medical College medicine laboratory provides Jaceosidin, content 98.1%, lot number: 121012); Bifendate (drop pill, Beijing consonance pharmaceutical factory, specification: 1.5mg, lot number: 120512); ALT/GPT test kit (Zhongsheng Beikong Biological Science & Technology Co., Ltd., lot number 110281); ASP/GOT test kit (Zhongsheng Beikong Biological Science & Technology Co., Ltd., lot number 110201); Ethanol (analytical pure, Yantai three and chemical reagents corporation, lot number: 050325).
Laboratory animal cleaning grade SD rat, male, body weight 150-200g, Shandong greenery researches on natural drugs development company Experimental Animal Center provides, qualified number: SYXK (Shandong) 20090020.
12 experimental techniques:
Rat 70, is divided into 7 groups at random, and namely Normal group, model group, bifendate group gavage 5.0mg/kg group, Jaceosidin gavage 2.0mg/kg group, 10.0mg/kg group, 50.0mg/kg group and 100.0mg/kg group often organize 10.Except Normal group, each group gives sc carbon tetrachloride stock solution 5ml/kg body weight first, later 2 sc25% carbon tetrachloride solution (olive oil is released) 2ml/kg body weight weekly, continuous 20 weeks.Normal group is given and same volume normal saline, prepare chronic liver damage model as stated above, when experiment the 8th week, start administration, successive administration 12 weeks, administration terminates rear use 20% urethane solution intraperitoneal injection of anesthesia, dissect, ventral aorta is taken a blood sample, and leaves and takes hepatic tissue, part is fixed with 10% neutral formalin solution, paraffin mass processed in 24-48h.Liver histopathology inspection adopts HE dyeing, chronic hepatic injury rat histopathology is changed and marks, liver cytoplasm puffing is divided into 0-3 level, hepatocyte fat variation is 0-3 level, hepatic necrosis is divided into 0-3 level, liver interstitial fibers hypertrophy is divided into 0-3 level, changes mark carry out rank test to rat histopathology.Blood sample centrifugal (4000rpm, 10min), collects serum, detects ALT/GPT, ASP/GOT active with medicine box.Data are used with data
represent, carry out statistical procedures to organize a t inspection.
1.3 experimental result
As shown in table 1, Jaceosidin gavage 2mg/kg group, 10.0mg/kg group, 50.0mg/kg group and 100.0mg/kg group obviously reduce GOT, GPT level and liver index (comparing with model control group, p<0.05 or 0.01).
Hepatic tissue pathology changes: result shows, CC14 Chronic Liver damage group rat, and normal hepatocytes leaflet structure destroys, there is steatosis widely, hepatic necrosis and interstitial fibers hypertrophy in various degree, and through the rat that Jaceosidin is treated, damaging pathological change obviously alleviates.As shown in table 2, Jaceosidin gavage 2mg/kg group, 10.0mg/kg group, 50.0mg/kg group and 100.0mg/kg group obviously reduce liver cytoplasm puffing, the change of hepatocyte fat, hepatic necrosis and liver interstitial fibers hypertrophy (comparing with model control group, p<0.05 or 0.01).Relatively These parameters, Jaceosidin gavage 50.0mg/kg group and Jaceosidin gavage 100.0mg/kg group no significant difference.
Table 1 Jaceosidin is to rat GOT, GPT level of chronic hepatic injury and liver exponential effect
Compare with model group
*p < 0.05,
*p < 0.01
The impact that table 2 Jaceosidin changes the rat histopathology of chronic hepatic injury
Compare with model group
*p < 0.05
*p < 0.01
Test example 2 Jaceosidin is on the impact of hepatic fibrosis
2.1 materials and animal
(pharmaceutical college of Binzhou Medical College medicine laboratory provides Jaceosidin, content 98.1%, lot number: 121012); Avandia (Rosiglitazone Maleate Tablets, GlaxoSmithKline company, lot number 111023)
HA (hyaluronic acid), LN (laminin，LN) and PcIII (type III collagen) radioimmunological kit are bought and are ground medical center in Shang Haihai; Hydroxyproline assay test kit builds up Bioengineering Research Institute purchased from Nanjing.
Laboratory animal cleaning grade SD rat, male, body weight 150-200g, Shandong greenery researches on natural drugs development company Experimental Animal Center provides, qualified number: SYXK (Shandong) 20090020.
2.2 experimental techniques:
Rat 70, is divided into 7 groups at random, i.e. Normal group, model group, rosiglitazone group gavage 8mg/kg group, Jaceosidin gavage 2.0mg/kg group, 10.0mg/kg group, 50.0mg/kg group and 100.0mg/kg group, often organizes 10.Rat Liver Fibrosis Model copies and respectively organizes method of disposal: with reference to the superfine method [Wu Mengchao copying Rat Liver Fibrosis Model of Wu Meng, Yang Guangshun. the research of function in rats with cirrhotic model copy. Chinese experimental surgery magazine, 1984, 1 (4): 145-147], except Normal group, each group of every 3d every 100g body weight subcutaneous injection 40% carbon tetrachloride oil solution 0.3ml, first dosage doubles, rats in normal control group every 3d subcutaneous injection oil solution 0.3ml/100g body weight, after 6 weeks, each group starts administration, successive administration 6 weeks, administration terminates rear use 20% urethane solution intraperitoneal injection of anesthesia, dissect, ventral aorta is taken a blood sample, leave and take hepatic tissue, part is fixed with 10% neutral formalin solution, paraffin mass processed in 24-48h.Liver histopathology inspection adopt HE dyeing, fibroplasia degree be divided into 0-4 level [Li Kun, Zhao Yuzhen, Zhu Qiushuan etc. ligustrazine is on the impact of the aged mouse heart, liver superoxide dismutase activity. Heilungkiang medical science, 1998; 21:4-5], measure HYP (hydroxyproline) in HA in serum (hyaluronic acid), LN (laminin，LN) and PcIII (type III collagen) and liver, HA, LN, PcIII, HYP measure by detection kit assay method.
2.3 experimental result
Pathological examination: rats in normal control group liver structure is normal; Within 12 weeks, all there is obvious fibrosis in model group rats liver; In each group of Jaceosidin, all comparatively model group is light for fibrosis.
Om observation: HE normal dyeing and the display of VG collagen staining hepatic tissue section, visible hepatic cell fattydegeneration in Liver Fibrosis Model control rats hepatic tissue, downright bad, cell infiltration; Collagen fiber deposition in portal area, Henny pipe hypertrophy; Fibrous connective tissue hypertrophy is obvious, and fibrous septum increases thick, and has typical pseudolobuli to be formed.Jaceosidin treatment group liver tissues of rats fibrous connective tissue hyperplasia degree alleviates, and fibrous septum attenuates, and pseudolobuli is formed not obvious.Rank test is carried out to each group of fibroplasia degree score value.The results are shown in Table 3, Jaceosidin gavage 2.0mg/kg group, 10.0mg/kg group, 50.0mg/kg group and 100.0mg/kg group obviously reduce fibroplasia degree (comparing with model control group, p<0.05 or 0.01).Relatively These parameters, Jaceosidin gavage 50.0mg/kg group and Jaceosidin gavage 100.0mg/kg group no significant difference.
T inspection is carried out to each group of HA, LN, PcIII, HYP.The results are shown in Table 4, Jaceosidin gavage 2.0mg/kg group, 10.0mg/kg group, 50.0mg/kg group and 100.0mg/kg group obviously reduce HA, LN, PcIII, HYP level (comparing with model control group, p<0.05 or 0.01).Relatively These parameters, Jaceosidin gavage 50.0mg/kg group and Jaceosidin gavage 100.0mg/kg group no significant difference.
Table 3 Jaceosidin is on the impact of rat liver fibrosis pathomorphism
Compare with model group,
▲p<0.05;
▲ ▲p<0.01.
Table 4 Jaceosidin is on the impact of liver tissues of rats with hepatic fibrosis HYP content and serum HA, LN and PCIII content
Compare with model group,
▲p<0.05;
▲ ▲p<0.01.
Claims (1)
1. Jaceosidin prevents in preparation or treats the application in the medicine of hepatic fibrosis, and when described Jaceosidin prevention or treatment hepatic fibrosis, oral administration is 500mg.
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| CN108096307B (en) * | 2014-06-04 | 2021-02-05 | 苏州大学 | Application of lindley eupatorium herb ethanol extract in preparing anti-hepatitis B virus medicine |
| WO2017146309A1 (en) | 2016-02-22 | 2017-08-31 | (주)오스티오뉴로젠 | Novel use of eupatilin as pharmaceutical composition for preventing and treating fibrosis by using epithelial-mesenchymal transition inhibitory activity thereof |
| WO2017146332A1 (en) * | 2016-02-22 | 2017-08-31 | (주)오스티오뉴로젠 | Novel use of chromone derivative as pharmaceutical composition for preventing and treating fibrosis by using epithelial-mesenchymal transition inhibitory activity thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20090079608A (en) * | 2008-01-18 | 2009-07-22 | 대전대학교 산학협력단 | Treatment for chronic inflammatory diseases comprising Artemisia extract |
| CN101933919A (en) * | 2010-07-01 | 2011-01-05 | 北京世纪博康医药科技有限公司 | Application of brown cyanidin |
| CN102697767A (en) * | 2012-04-20 | 2012-10-03 | 南京大学 | Application of Jaceosidin in preparation of medicine for preventing and treating insulin resistance, nonalcoholic fatty liver diseases and other diseases related to II-type diabetes mellitus |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20090079608A (en) * | 2008-01-18 | 2009-07-22 | 대전대학교 산학협력단 | Treatment for chronic inflammatory diseases comprising Artemisia extract |
| CN101933919A (en) * | 2010-07-01 | 2011-01-05 | 北京世纪博康医药科技有限公司 | Application of brown cyanidin |
| CN102697767A (en) * | 2012-04-20 | 2012-10-03 | 南京大学 | Application of Jaceosidin in preparation of medicine for preventing and treating insulin resistance, nonalcoholic fatty liver diseases and other diseases related to II-type diabetes mellitus |
Non-Patent Citations (1)
| Title |
|---|
| IL-17 Signaling in inflammatory, Kupffer Cells, and Hepatic Stellate Cells Exacerbates Liver Fibrosis;Fanli Meng et al.;《Gastroenterology》;20120930;第143卷(第3期);765-776.e1-3 * |
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