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Diagnostic agent and medicine comprising adamts13 as main ingredient

A liver function and disorder technology, applied in medical preparations containing active ingredients, disease diagnosis, peptide/protein components, etc., can solve problems such as unknown therapeutic drugs

Active Publication Date: 2018-08-28
KYOTO UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0039] So far, the relationship between ADAMTS13 and acute / chronic liver dysfunction, hepatic ischemia-reperfusion disorder, liver transplantation, and acute hepatic insufficiency / fulminant hepatitis has basically not been clarified, and the use of ADAMTS13 as a therapeutic drug for these diseases has not been known

Method used

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  • Diagnostic agent and medicine comprising adamts13 as main ingredient
  • Diagnostic agent and medicine comprising adamts13 as main ingredient
  • Diagnostic agent and medicine comprising adamts13 as main ingredient

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0193] Hepatic nonparenchymal cell function is drastically reduced by cryopreservation of transplanted livers

[0194] Whole livers were removed from rats (Wistar rats, male, 250-270 g), and then ADAMTS13 activity in liver tissue was measured after 6 hours and 24 hours of simple cold storage in HTK solution. As an object, the relative ratio of 100% relative to the average activity value of the normal liver of 4 cases of unpreserved rats was plotted ( figure 1 ). ADAMTS13 activity was measured by FRET method (FRETS-VWF73: Peptide Research Institute).

[0195] As a result, there was no significant difference in liver escape enzyme values ​​between the 2 groups of cold storage for 6 and 24 hours (there was no difference in the index of liver cell damage), and ADAMTS13 activity in the liver tissue was very sensitively inversely correlated with the cold storage time of the transplanted liver ( figure 1 ).

Embodiment 2

[0197] The basic state of liver dysfunction after chemotherapy in colorectal cancer is hepatic nonparenchymal cell disorder

[0198] Oxaliplatin, one of the key drugs in colorectal cancer chemotherapy, frequently causes liver dysfunction. Its morbid nature is sinusoidal obstructive syndrome (Sinusoidal Obstructive Syndrome: SOS) caused by the destruction of sinus wall cells caused by oxaliplatin. As an animal model of this SOS, using the most common single hyosostigline administration model, ADAMTS13 activity values ​​24 and 48 hours after administration of therapeutic drugs were compared and studied (n=5 for each group). and figure 1 In the same way as in the above method, after the liver tissue was collected, it was quantified by the FRET method.

[0199] NC: normal liver;

[0200] A24: 24 hours after administration of monosostigmine;

[0201] A48: 48 hours after administration of monosostigmine;

[0202] T24: 24 hours after the administration of monosostigmine + ther...

Embodiment 3

[0206] ADAMTS13 activity in blood is inversely correlated with the degree of hepatic insufficiency

[0207] From November 2012 to March 2013 in the Hepatobiliary Pancreatic / Transplantation Department of the Affiliated Hospital of Kyoto University School of Medicine, among 21 donors and recipients of adult living body partial liver transplantation, the preoperative ADAMTS13 activity value was monitored, which is the most commonly used in the world. MELD (Model for End-Stage Liver Disease) score and Child-Pugh score, which are indicators of hepatic insufficiency. As a result, the preoperative ADAMTS13 activity value showed a very perfect inverse correlation with MELD score and Child-Pugh score ( image 3 ). That is, it is considered that the ADAMTS13 activity value in the blood is effective as an index of hepatic insufficiency.

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Abstract

Provided is a novel use of ADAMTS13 in the medical field. Use of ADAMTS13 as a biomarker for monitoring the onset of hepatopathy, hepatic ischemia / reperfusion injury or hepatic function after liver transplantation; a method for examining hepatopathy, a method for examining hepatic ischemia / reperfusion injury or a method for examining hepatic function after liver transplantation, each method comprising measuring or monitoring ADAMTS13 activity in a sample obtained from a mammal; and a therapeutic agent for a disease selected from the group consisting of hepatopathy, hepatic ischemia / reperfusioninjury and hepatic dysfunction after liver transplantation, the agent comprising ADAMTS13 or a modification thereof.

Description

technical field [0001] The present invention relates to proteins in the field of medical drugs. Specifically, a full-length or partial fragment of a specific cleavage enzyme (hereinafter referred to as "ADAMTS13") related to von Willebrand Factor (von Willebrand Factor: hereinafter sometimes referred to as "vWF") involved in blood coagulation is clinically new uses of the field. Specifically, the present invention relates to the novel use of the full-length or partial fragments of ADAMTS13 in the fields of liver dysfunction, liver ischemia / reperfusion disorder and liver transplantation. Background technique [0002] The liver is an important organ responsible for metabolism, detoxification (detoxification of alcohol or harmful substances), and biological defense (immunity). Acute hepatitis mainly refers to a disease showing acute liver dysfunction caused by hepatitis virus infection, and its symptoms include jaundice, loss of appetite, vomiting, general fatigue, and fever....

Claims

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Application Information

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IPC IPC(8): G01N33/68A61K38/46A61P1/16C12M1/34C12N9/64C12Q1/37G01N33/50
CPCA61K38/46C12M1/34C12Q1/37C12N9/64G01N33/576G01N2333/96494G01N2800/08G01N2800/245A61P1/16Y02A50/30A61K38/4886G01N33/573G01N2800/085
Inventor 秦浩一郎上本伸二平尾浩史久保田丰成
Owner KYOTO UNIV
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