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Application of alverine to prepare drugs for preventing or treating portal hypertension

A portal hypertension and drug technology, applied in the field of medicine, can solve problems such as poor efficacy of treatment methods, and achieve the effect of reducing portal venous pressure

Active Publication Date: 2018-05-22
SECOND AFFILIATED HOSPITAL SECOND MILITARY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] At present, the clinical methods for the treatment of portal hypertension mainly include drug therapy and non-drug therapy. Drug therapy includes visceral vasoconstrictor drugs (such as antidiuretic hormone, somatostatin and its analogues, octreotide, vapreotide, etc., and non-selective therapy. β receptor blockers (such as proparol, carvedinol, etc.), intrahepatic blood vessel expansion drugs (such as nitrates that promote NO into the liver, simvastatin, etc., adrenergic receptor blockers prazosin , clonidine, etc., angiotensin blockers captopril, losartan, irbesartan, etc.), non-drug treatments include endoscopic variceal ligation (Endoscopicvaricealligation, EVL), transcervical Intrahepatic portosystemic shunt (Transjugularintrahepatic portosystemic shunt, TIPS), etc., but in view of the poor efficacy and complications of existing treatment methods, the treatment of portal hypertension still needs a drug or drug with significant efficacy and no obvious complications. treatment approach

Method used

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  • Application of alverine to prepare drugs for preventing or treating portal hypertension
  • Application of alverine to prepare drugs for preventing or treating portal hypertension
  • Application of alverine to prepare drugs for preventing or treating portal hypertension

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Effect of alverine on portal pressure in thioacetamide (TAA) model

[0041] 1. Experimental animals

[0042] 6-week-old male Sprague-Dawley (SD) rats with a body weight of about 180-200g are clean grade, purchased from Shanghai Slack Company, and the rats are bred in the Animal Experiment Center of the Second Military Medical University. Ethics committee approval.

[0043] 2. TAA model preparation and in vivo alverine intervention

[0044] 1) A total of 23 6-week-old male Sprague-Dawley (SD) rats weighing about 180-200 g were selected and randomly divided into normal control group (n=6) and model group (n=17). Rats in the model group were injected intraperitoneally with TAA0.2g / kg, 3 times a week, every other day. Rats in the control group were given intraperitoneal injection of normal saline at the same time point. Two groups of rats were injected continuously for 16 weeks to complete the model preparation. From week 17, rats in the model group were randomly divid...

Embodiment 2

[0069] Alverine in carbon tetrachloride (CCl 4 ) model on portal pressure

[0070] 1. Experimental animals

[0071] With embodiment 1.

[0072] 2. CCl 4 Model preparation and in vivo alverine intervention

[0073] 1) A total of 14 male Sprague-Dawley (SD) rats weighing about 180-200 g at the age of 6 weeks were selected and randomly divided into normal control group (n=4) and model group (n=10). Rats in the model group were given CCl 4 0.25ml / kg (dissolved in olive oil at a volume ratio of 1:3) was injected intraperitoneally, twice a week. Rats in the control group were injected intraperitoneally with olive oil at the same time point, and rats in the two groups were injected continuously for 7 weeks to complete the model preparation , the rats in the model group were randomly divided into the treatment control group (n=5) and the alverine group (n=5) from the 6th week.

[0074] 2) Alverine powder (purchased from TargetMol Company) was dissolved in 0.9% NaCl injection at ...

Embodiment 3

[0096] Different doses of alverine in carbon tetrachloride (CCl 4 ) model on portal pressure

[0097] 1. Experimental animals

[0098] The 6-week-old male Wister rats weighing about 180-200 g are clean grade and purchased from Shanghai Slack Company. The rats are bred in the Animal Experiment Center of the Second Military Medical University. All animal experiments have been approved by the Animal Ethics Committee of the Second Military Medical University.

[0099] 2. CCl 4 Model preparation and in vivo alverine intervention

[0100] 1) A total of 33 6-week-old male Wister rats weighing about 180-200 g were selected and randomly divided into normal control group (n=6) and model group (n=27). Rats in the model group were given CCl 4 0.25ml / kg (dissolved in olive oil at a volume ratio of 1:3) was injected intraperitoneally, twice a week, and rats in the normal control group were given intraperitoneal injection of olive oil at the same time point, and the rats in the two group...

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Abstract

The invention discloses an application of alverine to prepare drugs for preventing or treating portal hypertension. Three kinds of rat liver cirrhosis portal hypertension models including a thioacetamide model, a carbon tetrachloride model and a dimethylnitrosamine model are constructed, and the result of research shows that portal venous pressure of rats in different liver cirrhosis portal hypertension models can be obviously lowered after the rats in the three kinds of liver cirrhosis portal hypertension models are feed with 15mg / kg of alverine everyday. In this way, alverine can be used fortreating experimental liver cirrhosis portal hypertension and can further be used for treating portal hypertension such as esophageal-gastric varices, rupture and bleeding, abdominal dropsy and hepatic encephalopathy.

Description

technical field [0001] The present invention relates to the field of medicine and clinical medical technology. Specifically, the present invention relates to a kind of medicine that alverine is used in the preparation of prevention or treatment of portal hypertension such as esophagus-gastric varices and rupture bleeding, ascites, and hepatic encephalopathy. in the application. Background technique [0002] Alverine is a synthetic derivative of papaverine, which is a selective smooth muscle relaxant. Its chemical structural formula is shown in formula (I), molecular formula: C 20 h 27 N, chemical formula is N-ethyl-N-(3-phenylpropyl)amphetamine, molecular weight: 281.43, melting point <25°C, density 0.973g / cm 3 (Ghosh C, Jha V, Ahir R, Shah S, Shinde CP, Chakraborty BS. A rapid and most sensitive liquid chromatography / tandem massspectrometry method for simultaneous determination of alverine and its majormetabolite, para hydroxyalverine, in human plasma: application to ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/137A61P9/12
CPCA61K31/137A61K31/353A61K31/496A61K45/06A61P9/12
Inventor 张新谢渭芬朱昌鹏郑百男张俊平陈万生
Owner SECOND AFFILIATED HOSPITAL SECOND MILITARY MEDICAL UNIV