CN101822659A - Application of colchicin in preparing cholestatic liver disease drug - Google Patents
Application of colchicin in preparing cholestatic liver disease drug Download PDFInfo
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Abstract
The invention relates to application of colchicin in preparing drugs, in particular to application of colchicin in pharmacotherapy of cholestatic liver disease, the application of colchicin in preparing a cholestatic liver disease drug, and the application of colchicin in preparing the drug for treating gestation intrahepatic cholestasis syndrome, inner primary cirrhose biliaire, primary sclerosing cholangitis severe jaundice or immunity jaundice cholestatic liver disease. The colchicin can effectively lower liver injury and cholestasis caused by cholestatic liver disease, i.e. the colchicin can effectively treat cholestatic liver disease. The colchicin can effectively lighten hepatic cell necrosis, inflammatory cell infiltration and bile capillary hyperplasia caused by cholestasis. The colchicin can effectively increase bile acid, bilirubin and expression of phospholipid transporters BSEP, MRP2 and MDR3 in a bile duct, accelerates excretion of bile acid, bilirubin and phospholipid deposited in the body and reduces liver damage.
Description
Technical field
The present invention relates to the application of colchicine aspect pharmacy, the particularly application of colchicine in Drug therapy cholestasis hepatopathy.
Background technology
The colchicine source: colchicine is main effective ingredient and the toxic component in the Colchicum autumnale medical material, a kind of Tropolones alkaloid.Except that the Liliaceae Colchicum, equal other genus comprises that Gloriosa saperba L. belongs to (Gloriosa), benefit is warded off and also contained the colchicine Alkaloid hard the genus in (Iphigenia), An Guilashi Cymbidium (Auguillaria) and the Arisaema plants such as (Arisaema).Chemical name: N-(5,6,7,9-tetrahydrochysene-1,2,3,10-tetramethoxy-9-oxygen-benzo [a] heptalene-7-yl) acetamide, CAS:64-86-8.
Structure:
The main pharmacological of colchicine briefly is summarized as follows:
1. gout
Colchicine is mainly used in acute gout at present.Colchicine is to acute gouty arthritis antiinflammation selectively, all invalid to general pain, inflammation and chronic gout, its effect mainly is antiinflammatory, suppressing granulocyte soaks into, reason is the granulocytic activity that hinders that combines with the thin tubulin of grain, colchicine can suppress mitosis, destroys spindle, makes chromosome be stuck in metaphase of cell division.This undesired division that is caused by Colchicine is called Colchicine mitosis (c-mitosis).In such mitosis, though the chromosome lobe, cell does not divide, and can not form two daughter cells, thereby make chromosome doubling.
No matter colchicine is the formation that destroys or suppress spindle, effect all is for the moment.The autumn waters--limid eyes element can suppress the formation of spindle, causes cell not divide ,-Colchicine metabolism is after a while fallen then, no longer works, and cell continues division ,-be only " chromosome number doubles " (division of centromere) then.
2. antitumor action
Colchicine is the agent of cell mitogen strong inhibition, and is inhibited to the growth of tumor cell.Colchicine is brought into play the effect of tubulin polymerization inhibitive factor, can cause inside tumor new life's blood capillary damage and cause hemorrhagic extensively downright bad.The A of colchicine and C ring can combine with tubulin subunit 'beta '-tubulin, disturb the assembling process of tubulin, thereby make the microtubule egg compare depolymerization.Colchicine has now lacked and has used because the effect selectivity is lower, and toxicity is big.
3. nervous system
Colchicine has neurotoxicity, mainly combines with microtubule, suppresses the axoplasm transportation, and it is dead to cause neuron to go nutrition to degenerate.Colchicine can make the neuronal necrosis of tail shell nuclear.
Colchicine has the effect that strengthens or prolong hypnotic drug, can reduce body temperature, increases the sensitivity to the maincenter medicine, suppresses respiratory center, increases sympatheticomimetic reaction.Because the teleneuron corpusculum combines with colchicine, has disturbed the transhipment of neurotransmitter, thereby has changed nervimuscular function, has strengthened the gastrointestinal activity.
4. fibrosis/anti-hamartoplasia
Colchicine all demonstrates certain prevention and therapeutic effect to hepatic fibrosis, pulmonary fibrosis etc.To porcine blood serum immunity hepatic fibrosis rats and schistosomicide mice, colchicine has the effect of remarkable anti-hepatic fibrosis, obviously reduces various collagen content in the liver.Colchicine is inhibited to the formation of lung fibrosis in rats fibronectin.
Colchicine has obvious suppression inflammatory cell and anti-renal fibrosis effect, can prevent ciclosporin kidney region fibrosis that causes and the renal scars that the prevention bacterial infection causes to form, and can slow down glomerular sclerosis and interstitial fibrosis.
Set up the myocardial hypertrophy rat model with the method for ventral aorta constriction, colchicine can effectively suppress myocardial hypertrophy to be taken place, develops, and significantly downward modulation myocardial hypertrophy correlation factor is expressed simultaneously.
The colchicine lumbar injection can prevent the rabbit surgical adhesions.Colchicine is inhibited to the neointimal hyperplasia of people's great saphenous vein sheet of In vitro culture, and this inhibitory action only applies medicine in early days in cultivation could be significantly.
5. immune system and antiinflammatory action
Colchicine all has inhibitory action to propagation, differentiation, chemotactic and the inflammatory mediator release etc. of immunocyte.Significantly suppressor T cell and B cell function, particularly remarkable to the inhibition of the motion of leukocyte function and immunocyte and chemotaxis especially.Colchicine can also suppress immunocyte and epithelial cell TNF
α, the mRNA of IL-2, IL-6, TGF-β, grain-giant cell colony stimulating factor etc. and the expression and the secretion of protein level, but the generation of IL-1 β is had facilitation.The generation 5-lipoxidases such as release, inhibition activatory leukocyte and macrophage of colchicine by suppressing Cytolysosome enzymes such as leukocyte make the interior cAMP concentration of born of the same parents increase, promote prostaglandin to synthesize and release.Colchicine also has inhibitory action for gene expression and the protein synthesis of COX-2.Colchicine still can suppress basophilic granulocyte and macrophage secretion histamine, and dosage dependence property ground suppresses the rat macrophage TNF secretion that LPS stimulates
α, and colchicine acts on TNF
αSynthetic early stage, thus animal liver toxicity is had preventive effect.
Colchicine is as a kind of antigout drug commonly used and antineoplastic agent at present.
The gout usage and dosage: the treatment acute gout: oral first dose of 1mg, later 2～3 hours 0.5mg are until pain relief.Maximum dose: every day 3mg.Prevention gout acute attack: every day or the next day 0.5～1mg.
Antitumor usage and dosage: quiet: each 2～4ml (1～2mg), add 5% glucose 50ml, slowly instil, every day 1 time, 1 course of treatment 40～80ml.Quiet notes: each 2ml.With 25% glucose or isotonic saline solution 40ml, the dilution back is slow annotates.
Cholestasis be because the bile dyspoiesis and (or) a kind of clinical syndrome that flow obstacle caused.Be divided into alluvial of liver outer bladder juice and intrahepatic cholestasis.Liver outer bladder juice alluvial is meant the cholestasis of extrahepatic bile ducts system mechanics due to blocking; Intrahepatic cholestasis is meant that any cause of disease causes hepatocyte and/or bile capillary bile secretion dysfunction, or a series of pathology and clinical manifestation due to little bile duct diffusivity is blocked in the liver.
Cholate deposits in liver, all can cause hepar damnification and chronic cholestasis hepatopathy.Along with the progress of the state of an illness, be attended by serum alkaline phosphatase rising, jaundice and hypercholesterolemia usually, and progressively develop into hepatic fibrosis, liver cirrhosis even liver failure.
The cholestasis hepatopathy does not have specific drug at present, and ursodesoxycholic acid also can only alleviate the symptom of cholestasis as hepatoprotective commonly used.
Document is not seen the report of relevant colchicine in treatment cholestasis hepatopathy, and the inventor finds that first colchicine can treat the cholestasis hepatopathy.
Summary of the invention:
Goal of the invention
The inventor provides the application of a kind of colchicine in preparation treatment cholestasis hepatopathy medicine, and the application of colchicine in cholestasis hepatopathies such as treatment intrahepatic cholestasis of pregnancy syndrome, interior primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) icterus gravis and immunity jaundice is provided especially.
Technical scheme
Intrahepatic cholestasis of pregnancy syndrome, interior primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) icterus gravis or immunity jaundice cholestasis hepatopathy are one of common diseases of cholestasis hepatopathy.It is research PBC, PSC and icterus gravis animal model commonly used that α-ANIT (ANIT) causes the cholestasis model, it is the research intrahepatic cholestasis of pregnancy syndrome animal model of using always that the female alcohol of 17 alpha-acetylenes (EE) causes rat bile alluvial model, and the bile duct ligation causes the animal model that liver outer bladder juice alluvial model is the research obstructive jaundice used always.
Adopt α-ANIT (ANIT) to cause the cholestasis model, the female alcohol of 17 alpha-acetylenes (EE) causes rat bile alluvial model, the bile duct ligation causes the outer cholestasis model of rats'liver, colchicine with 50 and 100 μ g/kg is tested at above-mentioned three kinds of models, result of the test shows that colchicine obvious impairment occurs and reduces cholestasis effectively reducing liver, be better than clinical medicine ursodesoxycholic acid commonly used, thereby illustrate that colchicine can treat the cholestasis hepatopathy, increased the new purposes of colchicine.
The potential target spot of treatment cholestasis hepatopathy has:
One, reduces hepatocyte picked-up cholate and organic anion
Still the medicine that does not have at present specific minimizing hepatocyte picked-up cholate.Studies show that farnesol X receptor (FXR) agonist, as GW4064,6-ECDCA etc. may be the active drugs that reduces hepatocyte picked-up cholate.This class medicine can be reduced the expression of NTCP and OATPs, reduce hepatocyte enters cholestasis to bile acid and other organic anions liver, avoid the overload of hepatic bile acid, bilirubin and other bile components, but the side effect that causes serum bile acid and other organic anions to raise is arranged.On the contrary, bile acid multivalent chelator and ileum transport inhibitors then do not have this class side effect, and colchicine can raise the expression of liver bile acid receptor FXR, the expression of downward modulation NTCP and OATPs, reduce hepatocyte bile acid and other organic anions are entered the liver of cholestasis, reduce hepatic injury.
Two, promote the transhipment of bile salt in the hepatocyte
After bile salt and other material absorbing enter hepatocyte, rely on his hydrophobicity, mode by diffusion arrives the tubule top in Cytoplasm or lipid within endothelial cells film, rely on the bile acid transport body on the hepatocyte basolateral membrane, bile salt is drained into bile capillary as MRP2, MDR3, MRP3, OATP2C and BSEP etc.Studies show that, mostly some hereditary metabolic cholestasis diseases are because the defective of this type of transporter or sudden change cause, and the expression and the function of such transporter all reduced during chronic cholestasis, causes the endogenous of various genotoxic potentials and the drainage of exogenous material and is affected.Therefore promote bile salt transporter on the hepatocyte basolateral membrane expression and turn-over capacity, then can reduce cholate and organic anion in the hepatocyte accumulate and to hepatocellular toxicity.Colchicine can effectively increase the expression of bile acid in the bile duct, bilirubin and phospholipid transporter BSEP, MRP2 and MDR3, promotes the drainage of bile acid, bilirubin and the phospholipid of alluvial in the body, alleviates cholestasis.
Three, promote the excretion of bile duct cell
The significance of bile duct cell excretion function is to dilute bile and cleans bile duct.During as cystic fibrosis, because coding Ca
2+The cftr gene sudden change of the chloride channel that relies on causes the HCO that chloride ion relies on
3 -Secrete impaired.And in PBC, then have the secretion and the Cl of bile duct cell bicarbonate
2HCO
3 -Exchange impaired.Stimulate bile duct cell to strengthen then can reducing the toxicity of bile acid to bile duct cell to the excretion of cholate.Colchicine can effectively increase the drainage of bile duct cell to bile acid, bilirubin and phospholipid, thereby increases bile acid dependency gallbladder stream (BSDF) and non-bile acid dependency gallbladder stream (BSIF), promotes the bile duct cell excretion.
Four, protection bile duct epithelial cell
The protection bile duct epithelial cell is avoided the toxicity damage of bile acid, is the important measures of treatment based on the chronic cholestasis disease (as PBC, PSC) of bile duct injury.Bile duct epithelial cell is the target spot of immune-mediated damage in this class disease, and the hydrophobicity bile acid of high concentration has cytotoxicity, can further increase the weight of the damage of bile duct epithelial cell.The cholestasis disease that some are rare, the carrying out property familial intrahepatic cholestasis III type due to lacking as heritability MDR3, owing to lack phospholipid in the bile, the micelle that can not form bile-phospholipid reduces biliary toxic action.Therefore improve the unbalance toxicity that then can alleviate bile acid of bile acid and phospholipid.Colchicine can effectively raise liver MDR3 and express, and promotes that hepatocyte drains phospholipid, the concentration of phospholipid in the rising bile, thus the protection bile duct epithelial cell reduces serum levels of ALP and GGT level, reduces hepatic injury.
Beneficial effect
1, colchicine can effectively reduce hepatic injury and the cholestasis that the cholestasis hepatopathy causes, promptly can treat the cholestasis hepatopathy effectively.
2, colchicine can effectively alleviate hepatic necrosis, inflammatory cell infiltration and the bile capillary hypertrophy that cholestasis causes.
3, colchicine can effectively increase the expression of bile acid in the bile duct, bilirubin and phospholipid transporter BSEP, MRP2 and MDR3, promotes the drainage of bile acid, bilirubin and the phospholipid of alluvial in the body, and the protection bile duct epithelial cell reduces hepatic injury.
4, colchicine can raise the expression of liver bile acid receptor FXR, and the expression of downward modulation NTCP and OATPs reduces hepatocyte bile acid and other organic anions are entered the liver of cholestasis, reduces hepatic injury.
The specific embodiment
Embodiment 1, α-ANIT (ANIT) is caused rat bile alluvial effect
α-ANIT (ANIT) causes the model that the cholestasis model is research intrahepatic cholestasis classics.It is cholestasis to occur after adopting ANIT 50-100mg/kg gastric infusion 12h that ANIT causes the rat bile alluvial, occurs hepatic injury and jaundice behind the 24h.Experimental program: 30 220-250g male Wistar rats are divided into 5 groups at random, 6 every group: normal control group, model group (ANIT 50mg/kg irritates stomach), melatonin 50mg/kg irritate stomach treatment group, colchicine 50 and 100 μ g/kg lumbar injection treatment groups.Administration group prevention administration 5 days, overnight fasting after the 5th day, give ANIT modeling, 48h difference eye socket blood sampling 0.5ml surveys glutamate pyruvate transaminase (ALT), glutamic oxaloacetic transaminase, GOT (AST), alkali phosphatase (ALP), gamma-amino transpeptidase (GGT), total bilirubin (TBIL) and TOTAL BILE ACID TBA (TBA) after modeling then.Get liver and fix with neutral formalin, paraffin embedding is made tissue slice, does the expression that H-E dyeing and SABC detect FXR, BSEP, MRP2 and MDR3 respectively.Experimental result shows, model group ALT, AST, ALP, GGT, the every biochemical indicator of TBIL, TBA all significantly raise, hepatic necrosis and inflammatory cell infiltration appear in liver, the expression of FXR, BSEP, MRP2 and MDR3 is lowered, show that obvious impairment and cholestasis appear in liver, and 2 treatment groups of colchicine all can alleviate hepatic necrosis and inflammatory cell infiltration, increase the every damage blood biochemistry index of expression obvious reduction in various degree of BSEP, MRP2 and MDR3.Blood biochemistry the results are shown in following table.
*Compare with normal group p＜0.01;
#P＜0.05,
##Compare with model group p＜0.01.
Embodiment 2, the female alcohol of 17 alpha-acetylenes (EE) is caused rat bile alluvial effect
Adopt the female alcohol of 17 alpha-acetylenes (EE) to cause rat bile alluvial effect modeling.The EE modeling is a research trimester of pregnancy cholestasis animal model commonly used, adopts EE 5mg/kg subcutaneous injection promptly can cause cholestasis in continuous 5 days.Experimental program: 30 male rats are divided into following 5 groups at random according to body weight, 6 every group: and normal control group, model group (EE 5mg/kg, sc), ursodesoxycholic acid 50mg/kg irritates stomach treatment group, colchicine 50 and 100 μ g/kg lumbar injection treatment groups.Wherein EE modeling administration is 5 days, and 1h gives colchicine before the modeling, overnight fasting after the last administration, and eye socket blood sampling 1ml surveys ALT, AST, ALP, GGT, TBIL and TBA.Get liver and fix with neutral formalin, paraffin embedding is made tissue slice, does the expression that H-E dyeing and SABC detect FXR, BSEP, MRP2 and MDR3 respectively.Experimental result shows, model group animal serum ALP, GGT, TBIL and TBA level significantly raise, a small amount of hepatic necrosis appears in liver, the expression of FXR, BSEP, MRP2 and MDR3 reduces, tangible cholestasis and bile duct injury take place in prompting, and 2 treatment groups of colchicine all can be in various degree the every damage criterion of obvious reduction, alleviate the every damage blood biochemistry index of expression obvious reduction in various degree that hepatic necrosis increases BSEP, MRP2 and MDR3.Blood biochemistry the results are shown in following table.
*P＜0.05,
*Compare with normal group p＜0.01;
#P＜0.05,
##Compare with model group p＜0.01.
Embodiment 3, ligation causes liver outer bladder juice alluvial effect to bile duct
Adopt the bile duct ligation to cause liver outer bladder juice alluvial effect modeling.Just occurred obstructive jaundice after the ligation of rat common bile duct in second day, rat bile duct ligation model is the research liver used always the animal model of alluvial property jaundice outward.Experimental program: 32 of SD rats, male and female half and half, lumbar injection dosage is that the 400mg/kg chloral hydrate anesthesia is cut along hunter's line, separate ductus choledochus, dual ligation is also cut off from the centre, and wherein 6 of matched groups adopt the sham-operation method, only separate not ligation of bile duct, sew up with surgical thread.Survive 24 two days later.Be divided into: matched group, model group, ursodesoxycholic acid 50mg/kg irritate stomach treatment group, colchicine 50 and 100 μ g/kg lumbar injection treatment groups.Successive administration 5 days, the 5th day overnight fasting, femoral artery are got blood and are surveyed blood biochemistry.Get liver and fixedly do histopathologic slide, do the expression that H-E dyeing and SABC detect BSEP, MRP2 and MDR3 respectively with neutral formalin.Experimental result shows, model group animal serum ALT, AST, ALP, GGT and TBA level significantly raise, hepatic necrosis appears in liver, inflammatory cell infiltration and bile capillary hypertrophy, the expression of FXR, BSEP, MRP2 and MDR3 reduces, tangible cholestasis and hepar damnification take place in prompting, and the every damage criterion of obvious reduction that 2 treatment groups of colchicine all can be in various degree.Alleviate hepatic necrosis, inflammatory cell infiltration and bile capillary hypertrophy increase the expression of FXR, BSEP, MRP2 and MDR3, obviously reduce every damage blood biochemistry index.Blood biochemistry the results are shown in following table.
*Compare with normal group p＜0.01;
#P＜0.05,
##Compare with model group p＜0.01.
Claims (2)
1. the application of colchicine in preparation treatment cholestasis hepatopathy medicine.
2. the application of colchicine in preparation treatment intrahepatic cholestasis of pregnancy syndrome, interior primary biliary cirrhosis, primary sclerosing cholangitis icterus gravis or immunity jaundice cholestasis hepatopathy medicine.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102274232A (en) * | 2011-06-22 | 2011-12-14 | 南京理工大学 | Application of adenosine receptor A1 antagonist in preparing medicine |
| CN108456152A (en) * | 2017-02-22 | 2018-08-28 | 中国药科大学 | Colchicine derivative, preparation method and medical usage |
| CN109125308A (en) * | 2018-08-17 | 2019-01-04 | 上海市浦东新区浦南医院 | Colchicin is in the new application for preventing and treating ischemic cerebrovascular disease |
| CN109964129A (en) * | 2016-09-16 | 2019-07-02 | 库里斯特转运体解决方案有限责任公司 | Cause the method and system of systemic toxicity or hepatotoxic potential for screening candidate compound |
| CN113226295A (en) * | 2018-10-18 | 2021-08-06 | 阿沃林特有限公司 | Use of SGLT2 inhibitor in treatment of primary sclerosing cholangitis |
| CN113876789A (en) * | 2021-10-28 | 2022-01-04 | 兰州大学第一医院 | New application of Licraside in preparation of medicine for treating cholestasis |
| CN114630662A (en) * | 2020-10-08 | 2022-06-14 | 科罗姆生物科技有限公司 | Pharmaceutical composition for preventing or treating cholestatic liver disease comprising beta-lapachone as an effective ingredient |
| CN114903905A (en) * | 2021-02-09 | 2022-08-16 | 中国人民解放军陆军军医大学第二附属医院 | Application of glycodeoxycholic acid in preparation of medicine for treating intrahepatic cholestasis and medicine composition of glycodeoxycholic acid |
| CN114929214A (en) * | 2019-11-22 | 2022-08-19 | 阿沃林特有限公司 | Application of SGLT2 inhibitor in treatment of primary biliary cholangitis |
| CN115414331A (en) * | 2022-10-12 | 2022-12-02 | 广东彼迪药业有限公司 | Colchicine tablet |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101440113A (en) * | 2007-11-19 | 2009-05-27 | 中国人民解放军军事医学科学院毒物药物研究所 | Colchicine derivative-bile acid coupling compounds and medical use thereof |
-
2010
- 2010-05-11 CN CN 201010168556 patent/CN101822659A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101440113A (en) * | 2007-11-19 | 2009-05-27 | 中国人民解放军军事医学科学院毒物药物研究所 | Colchicine derivative-bile acid coupling compounds and medical use thereof |
Non-Patent Citations (3)
| Title |
|---|
| 《亚太传统医药》 20090630 刘良余 原发性胆汁性肝硬化研究进展 151-152 1-2 第5卷, 第6期 2 * |
| 《国外医学消化系统疾病分册》 19961231 李超群，等 秋水仙碱和熊去氧胆酸治疗原发性胆汁性肝硬化的安慰剂对照试验 63-64 1-2 第16卷, 第1期 2 * |
| 《胃肠病学》 20071231 尧颖，等 原发性硬化性胆管炎的治疗 380-382 1-2 第12卷, 第6期 2 * |
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| CN102274232A (en) * | 2011-06-22 | 2011-12-14 | 南京理工大学 | Application of adenosine receptor A1 antagonist in preparing medicine |
| CN109964129B (en) * | 2016-09-16 | 2023-04-14 | 库里斯特转运体解决方案有限责任公司 | Methods and systems for screening candidate compounds for potential to cause systemic toxicity or hepatotoxicity |
| CN109964129A (en) * | 2016-09-16 | 2019-07-02 | 库里斯特转运体解决方案有限责任公司 | Cause the method and system of systemic toxicity or hepatotoxic potential for screening candidate compound |
| CN108456152A (en) * | 2017-02-22 | 2018-08-28 | 中国药科大学 | Colchicine derivative, preparation method and medical usage |
| WO2018153212A1 (en) * | 2017-02-22 | 2018-08-30 | 中国药科大学 | Colchicine derivatives, preparation method therefor and medical use thereof |
| CN108456152B (en) * | 2017-02-22 | 2020-07-14 | 中国药科大学 | Colchicine derivative, preparation method and medical application thereof |
| CN109125308A (en) * | 2018-08-17 | 2019-01-04 | 上海市浦东新区浦南医院 | Colchicin is in the new application for preventing and treating ischemic cerebrovascular disease |
| CN113226295A (en) * | 2018-10-18 | 2021-08-06 | 阿沃林特有限公司 | Use of SGLT2 inhibitor in treatment of primary sclerosing cholangitis |
| CN114929214A (en) * | 2019-11-22 | 2022-08-19 | 阿沃林特有限公司 | Application of SGLT2 inhibitor in treatment of primary biliary cholangitis |
| CN114630662A (en) * | 2020-10-08 | 2022-06-14 | 科罗姆生物科技有限公司 | Pharmaceutical composition for preventing or treating cholestatic liver disease comprising beta-lapachone as an effective ingredient |
| CN114903905A (en) * | 2021-02-09 | 2022-08-16 | 中国人民解放军陆军军医大学第二附属医院 | Application of glycodeoxycholic acid in preparation of medicine for treating intrahepatic cholestasis and medicine composition of glycodeoxycholic acid |
| CN114903905B (en) * | 2021-02-09 | 2024-04-02 | 中国人民解放军陆军军医大学第二附属医院 | Application of glycodeoxycholic acid in preparing medicament for treating intrahepatic cholestasis and pharmaceutical composition thereof |
| CN113876789A (en) * | 2021-10-28 | 2022-01-04 | 兰州大学第一医院 | New application of Licraside in preparation of medicine for treating cholestasis |
| CN115414331A (en) * | 2022-10-12 | 2022-12-02 | 广东彼迪药业有限公司 | Colchicine tablet |
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