CN103655544A - Application of jaceosidin in preparation of drugs used for preventing or treating chronic liver injury and hepatic fibrosis - Google Patents
Application of jaceosidin in preparation of drugs used for preventing or treating chronic liver injury and hepatic fibrosis 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 46
- 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 46
- 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 46
- XRHHDQSPFPQKMS-UHFFFAOYSA-N sudachitin Natural products C1=C(O)C(OC)=CC(C=2OC3=C(OC)C(O)=C(OC)C(O)=C3C(=O)C=2)=C1 XRHHDQSPFPQKMS-UHFFFAOYSA-N 0.000 title claims abstract description 46
- 231100000012 chronic liver injury Toxicity 0.000 title claims abstract description 20
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- 239000003814 drug Substances 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title abstract description 6
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- 229940079593 drug Drugs 0.000 title abstract description 4
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- 238000003304 gavage Methods 0.000 description 14
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 8
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- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 7
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- 238000011160 research Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
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- 238000011161 development Methods 0.000 description 5
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
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- 108010043741 Collagen Type VI Proteins 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- 206010019799 Hepatitis viral Diseases 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical group C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FINHMKGKINIASC-UHFFFAOYSA-N Tetramethylpyrazine Chemical compound CC1=NC(C)=C(C)N=C1C FINHMKGKINIASC-UHFFFAOYSA-N 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
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- 238000007689 inspection Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 210000005228 liver tissue Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- JMZOMFYRADAWOG-UHFFFAOYSA-N methyl 7-methoxy-4-(7-methoxy-5-methoxycarbonyl-1,3-benzodioxol-4-yl)-1,3-benzodioxole-5-carboxylate Chemical compound COC(=O)C1=CC(OC)=C2OCOC2=C1C1=C2OCOC2=C(OC)C=C1C(=O)OC JMZOMFYRADAWOG-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
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- 231100000915 pathological change Toxicity 0.000 description 2
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- 230000001007 puffing effect Effects 0.000 description 2
- SUFUKZSWUHZXAV-BTJKTKAUSA-N rosiglitazone maleate Chemical compound [H+].[H+].[O-]C(=O)\C=C/C([O-])=O.C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O SUFUKZSWUHZXAV-BTJKTKAUSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- 231100000240 steatosis hepatitis Toxicity 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 201000001862 viral hepatitis Diseases 0.000 description 2
- 241001435059 Artemisia argyi Species 0.000 description 1
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- 241000208838 Asteraceae Species 0.000 description 1
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- 241000735527 Eupatorium Species 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
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- 210000001015 abdomen Anatomy 0.000 description 1
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- 244000030166 artemisia Species 0.000 description 1
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- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
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- 229930003935 flavonoid Natural products 0.000 description 1
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- 239000008101 lactose Substances 0.000 description 1
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- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides novel pharmaceutical application of jaceosidin and specifically relates to application of jaceosidin in preparation of drugs used for preventing or treating chronic liver injury and hepatic fibrosis. In the above-mentioned application, the dosage range of applied jaceosidin is 20 to 1000 mg, preferably, 20 to 500 mg.
Description
Technical field
The present invention is the medicine in a kind of hepatopathy field, thereby content relates to Jaceosidin, suppresses the Fibrotic generation development prevention of chronic hepatic injury regulating liver-QI or treatment 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 one of society principal diseases of threatening human health.China is hepatopathy big country, according to recent statistics viral hepatitis and hepatitis B virus carriers, has 14% above population to infect in the middle of population of China.Aggravation develops into hepatic fibrosis, hepatic ascites, liver abdomen and hepatocarcinoma.Die from every year liver cirrhosis, the patient of hepatocarcinoma just has more than 100 ten thousand.
Hepatic fibrosis is the common pathologic basis of various chronic hepatopathys, is the important stage of liver cirrhosis generating process, often by reasons such as chronic inflammatory disease, cholestasis, immunologic injuries in liver, is caused.Have data to show that the sickness rate of hepatic fibrosis is 85.1%, hepatic fibrosis sustainable development will have 25%-40% to develop into liver cirrhosis.Studies confirm 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 (Folium Artemisiae Argyi) derives from the dried leaves of Compositae sagebruss Chinese mugwort (Artemisia argyi Levl.et Vant.), is clinical conventional Chinese medicine.Jaceosidin is from Folium Artemisiae Argyi, to extract the single compound [Tang Shengan obtaining, 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 [Clavin M, Gorzalczany S, Macho A
e, Ferraro G, Acevedo C, Martino V.Anti-inflammatory activity of flavonoids from Eupatorium amottianum.J Ethnopharmaco1.2007; 112 (3): 585-589.], but Jaceosidin has no report in preparation prevention or the Fibrotic pharmacological action for the treatment of chronic hepatic injury regulating liver-QI.The inventor finds that by a large amount of research Jaceosidin has obvious effect to chronic hepatic injury and hepatic fibrosis.Based on this, inventor, by a large amount of experimentatioies, has confirmed the application of Jaceosidin in prevention or treatment acute and chronic liver injury and hepatic fibrosis.
Summary of the invention
The invention provides the application of Jaceosidin in the medicine of prevention or treatment 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; Preferred 20～500mg.
The present invention also provides the medicine being comprised of Jaceosidin and pharmaceutically acceptable carrier or adjuvant, and this medicine can be prepared into tablet, capsule with pharmacy conventional method, preferably with tablet form, exists.
The specific embodiment
Preparation example 1: prepare Jaceosidin
The Folium Artemisiae Argyi that 1kg is dry is pulverized, with the alcohol heating reflux of 6 times of amounts 95%, extract 3 times, each 6h, filter, merging filtrate, be evaporated to extractum shape, obtain extract, add after appropriate distilled water suspendible, in the separatory funnel of 10L, with ethyl acetate, extract, collect extract with silica gel column chromatography (silica gel 600g, 300-400 order) separation, uses CH2C12 → CH2C12:EtoAc (5:1 → 2:1) → EtoAc → MeOH gradient elution successively, by TLC, merges similar components, cross silicagel column normal pressure post, obtain Jaceosidin 460mg.
Embodiment 2 Jaceosidin tablet preparations
After taking 20.0g Jaceosidin, 55.0g Icing Sugar, 100.0g lactose and the abundant mix homogeneously of 23.0g carboxymethyl starch sodium, cross 100 mesh sieves, add appropriate 3%PVP
k30aqueous solution is soft material processed in right amount, and 20 mesh sieves are granulated, and 60 ℃ are dried 3 hours, and 18 mesh sieve granulate, add 2.0g magnesium stearate, scrobicula punching press after mix homogeneously, and the heavily about 200mg of adjustment sheet, obtains.
The specific embodiment
The impact of test example 1 Jaceosidin on 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 San He chemical reagents corporation, lot number: 050325).
The clean level of laboratory animal 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:
70 of rats, are divided into 7 groups at random, and 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 organize 10 every group.Except Normal group, each group gives sc carbon tetrachloride stock solution 5ml/kg body weight first, 2 sc25% carbon tetrachloride solutions (olive oil is released) 2ml/kg body weight weekly later, continuous 20 weeks.Normal group is given and same volume normal saline, prepare as stated above chronic hepatic injury model, in experiment, in the time of the 8th week, start administration, successive administration 12 weeks, administration finishes rear use 20% urethane solution intraperitoneal injection of anesthesia, dissect, ventral aorta blood sampling, 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 marked, 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, rat histopathology is changed to mark and carry out rank test.Blood sample centrifugal (4000rpm, 10min), collects serum, detects ALT/GPT, ASP/GOT active with medicine box.Data are used with data
represent, to organize a t check, carry out statistical procedures.
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 (with model control group comparison, 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 the rat for the treatment of through Jaceosidin, 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 (with model control group comparison, p<0.05 or 0.01).Compare These parameters, Jaceosidin gavage 50.0mg/kg group and Jaceosidin gavage 100.0mg/kg group no significant difference.
Table 1 Jaceosidin is on the rat GOT of chronic hepatic injury, GPT level and the impact of liver index
With model group comparison
*p < 0.05,
*p < 0.01
The impact that table 2 Jaceosidin changes the rat histopathology of chronic hepatic injury
With model group comparison
*p < 0.05
*p < 0.01
The impact of test example 2 Jaceosidins on 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, Glaxo SmithKline company, lot number 111023)
HA (hyaluronic acid), LN (laminin，LN) and PcIII (III Collagen Type VI) radioimmunological kit are bought in Shang Haihai and are ground medical center; Hydroxyproline assay test kit builds up Bioengineering Research Institute purchased from Nanjing.
The clean level of laboratory animal 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:
70 of rats, are 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, 10 every group.Rat Liver Fibrosis Model copies and respectively organizes method of disposal: with reference to the superfine method [Wu Mengchao that copies 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 organizes the every 100g body weight of every 3d subcutaneous injection 40% carbon tetrachloride oil solution 0.3ml, first dosage doubles, the every 3d subcutaneous injection of rats in normal control group oil solution 0.3ml/100g body weight, after 6 weeks, each group starts administration, successive administration 6 weeks, administration finishes rear use 20% urethane solution intraperitoneal injection of anesthesia, dissect, ventral aorta blood sampling, leave and take hepatic tissue, part is fixed with 10% neutral formalin solution, paraffin mass processed in 24-48h.Liver histopathology inspection adopts HE dyeing, fibroplasia degree be divided into 0-4 level [Li Kun, Zhao Yuzhen, Zhu Qiushuan etc. the impact of ligustrazine on the aged mouse heart, liver superoxide dismutase activity. Heilungkiang medical science, 1998; 21:4-5], HYP (hydroxyproline) in HA in serum (hyaluronic acid), LN (laminin，LN) and PcIII (III Collagen Type VI) and liver is measured, 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 rat liver; In each group of Jaceosidin, fibrosis is all light compared with model group.
Om observation: HE normal dyeing and VG collagen staining hepatic tissue section show, visible hepatic cell fattydegeneration in Liver Fibrosis Model control rats hepatic tissue, necrosis, cell infiltration; Collagen fiber deposition in portal area, Henny manages hypertrophy; Fibrous connective tissue hypertrophy is obvious, and fibrous septum increases thick, and has typical pseudolobuli to form.Jaceosidin treatment group liver tissues of rats fibrous connective tissue hyperplasia degree alleviates, and fibrous septum attenuates, and pseudolobuli forms not obvious.Each group fibroplasia degree score value is carried out to rank test.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 (with model control group comparison, p<0.05 or 0.01).Compare These parameters, Jaceosidin gavage 50.0mg/kg group and Jaceosidin gavage 100.0mg/kg group no significant difference.
Each group HA, LN, PcIII, HYP are carried out to T check.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 (with model control group comparison, p<0.05 or 0.01).Compare These parameters, Jaceosidin gavage 50.0mg/kg group and Jaceosidin gavage 100.0mg/kg group no significant difference.
The impact of table 3 Jaceosidin on rat liver fibrosis pathomorphism
With model group comparison,
▲p<0.05;
▲ ▲p<0.01.
The impact of table 4 Jaceosidin on liver tissues of rats with hepatic fibrosis HYP content and serum HA, LN and PCIII content
With model group comparison,
▲p<0.05;
▲ ▲p<0.01.
Claims (5)
1. the application of Jaceosidin in the medicine of prevention or treatment chronic hepatic injury and hepatic fibrosis.
2. the application of Jaceosidin in prevention or treatment chronic hepatic injury.
3. the application of Jaceosidin in prevention or treatment hepatic fibrosis
4. Jaceosidin is when for chronic hepatic injury and treating liver fibrosis, and its using dosage scope is 20mg～1000mg; Preferred using dosage 20～500mg.
5. the medicine being formed by Jaceosidin and pharmaceutically acceptable carrier or adjuvant, this medicine can be prepared into tablet, capsule with pharmacy conventional method; Preferably with tablet form, exist.
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| CN201310658931.6A CN103655544B (en) | 2013-12-02 | 2013-12-02 | The application of Jaceosidin in preparation prevention or the Fibrotic medicine for the treatment of chronic hepatic injury regulating liver-QI |
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| CN201310658931.6A CN103655544B (en) | 2013-12-02 | 2013-12-02 | The application of Jaceosidin in preparation prevention or the Fibrotic medicine for the treatment of chronic hepatic injury regulating liver-QI |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20170239211A1 (en) * | 2016-02-22 | 2017-08-24 | Osteoneurogen Inc. | Use of chromone derivative as pharmaceutical composition for prevention and treatment of fibrosis using emt inhibitory activity |
| KR101780456B1 (en) | 2016-02-22 | 2017-09-21 | (주)오스티오뉴로젠 | New use of eupatilin and chromen derivatives as pharmaceutical composition for prevention and treatment of fibrosis via EMT inhibitory activity |
| CN108113985A (en) * | 2014-06-04 | 2018-06-05 | 苏州大学 | Application of the eupatorium lindleynun var. trifoliolatum flavones position in anti-hepatic-B virus medicine is prepared |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108113985A (en) * | 2014-06-04 | 2018-06-05 | 苏州大学 | Application of the eupatorium lindleynun var. trifoliolatum flavones position in anti-hepatic-B virus medicine is prepared |
| CN108113985B (en) * | 2014-06-04 | 2020-07-21 | 苏州大学 | Application of eupatorium lindleyanum flavone part in preparation of anti-hepatitis B virus medicines |
| US20170239211A1 (en) * | 2016-02-22 | 2017-08-24 | Osteoneurogen Inc. | Use of chromone derivative as pharmaceutical composition for prevention and treatment of fibrosis using emt inhibitory activity |
| 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 |
| KR101780456B1 (en) | 2016-02-22 | 2017-09-21 | (주)오스티오뉴로젠 | New use of eupatilin and chromen derivatives as pharmaceutical composition for prevention and treatment of fibrosis via EMT inhibitory activity |
| CN108883088A (en) * | 2016-02-22 | 2018-11-23 | 欧斯特奥纽罗根有限公司 | Using the Epithelial and stromal of chromone derivative conversion inhibitory activity as fibrosis prevention and the new application for the treatment of pharmaceutical composition |
| US10744113B2 (en) * | 2016-02-22 | 2020-08-18 | Osteoneurogen Inc. | Use of chromone derivative as pharmaceutical composition for prevention and treatment of fibrosis using EMT inhibitory activity |
| US10744114B2 (en) | 2016-02-22 | 2020-08-18 | Osteoneurogen Inc. | Use of eupatilin as pharmaceutical composition for prevention and treatment of fibrosis using EMT inhibitory activity |
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|---|---|
| CN103655544B (en) | 2016-03-30 |
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