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Dipeptide derivatives and their applications

A technology of uses and drugs, applied in the directions of dipeptide components, peptides, drug combinations, etc., can solve problems such as unsatisfactory treatment methods and lack of liver failure.

Active Publication Date: 2015-09-30
BEIJING CONTINENT PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] However, the above-mentioned treatment methods are still unsatisfactory. In addition, there is still a lack of satisfactory effective drugs for liver failure in the world.

Method used

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  • Dipeptide derivatives and their applications
  • Dipeptide derivatives and their applications
  • Dipeptide derivatives and their applications

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] Give F573 after modeling

[0086] 1. Method

[0087] Wistar rats were randomly divided into 6 groups: normal control group, model group, positive drug N-acetylcysteine ​​(NAC 155mg / kg) group and F573 high-dose (H 5.0mg / kg), medium-dose (M 2.5 mg / kg), low-dose (L 1.25mg / kg) groups, 10 rats in each group, except the blank group, each group was intraperitoneally injected (ip) with D-Gal500mg / kg and LPS 20μg / kg, and the model was established for 2 Hours later, each group ip corresponding NAC and F573, and the blank group was given the corresponding volume of solvent, namely:

[0088] ①Blank group: ip solvent (0.5% CMC physiological saline), ip 2ml / 200g according to body weight

[0089] ②Model group: ip D-Gal 500mg / kg and LPS 20μg / kg and ip solvent 1ml / 200g

[0090] ③NAC group: ip D-Gal 500mg / kg and LPS 20μg / kg+NAC 155mg / kg

[0091] ④F573H group: ip D-Gal 500mg / kg and LPS 20μg / kg+F573 5.0mg / kg

[0092] ⑤F573M group: ip D-Gal 500mg / kg and LPS 20μg / kg+F573 2.5mg / kg

[00...

Embodiment 2

[0150] Modeling while giving F573

[0151] 1. Method

[0152] Repeat Example 1, the difference is: 70 Wistar rats are randomly divided into 7 groups: normal control group, model group, positive drug N-acetylcysteine ​​(NAC 155mg / kg) group and F573 high dose (H : 5mg / kg), medium dose (M: 2.5mg / kg), low dose (L: 1.25mg / kg) and very low dose (LL: 0.625mg / kg) groups, 10 rats in each group, except the blank group In addition, the modeling drugs D-Gal 500 mg / kg and LPS 20 μg / kg were injected intraperitoneally (ip) in each group, and the corresponding NAC and F573 were administered in each group ip at the same time as the modeling (0 hour), and the corresponding volume of solvent was given to the blank group, namely:

[0153] ①Blank group: ip solvent (0.5% CMC physiological saline), ip 2ml / 200g according to body weight

[0154] ②Model group: ip D-Gal 500mg / kg and LPS 20μg / kg+ip solvent 1ml / 200g

[0155] ③NAC group: ip D-Gal 500mg / kg and LPS 20μg / kg+NAC 155mg / kg

[0156] ④F573H gr...

Embodiment 3

[0209] Give F573 before modeling

[0210] 1. Method

[0211] Repeat Example 1, the difference is: 4 hours before modeling, each group ip corresponding NAC, F573, and the blank group was given a corresponding volume of solvent, namely:

[0212] ①Blank group: ip solvent (0.5% CMC physiological saline), ip 2ml / 200g according to body weight

[0213] ②Model group: ip D-Gal 500mg / kg and LPS 20μg / kg+ip solvent 1ml / 200g

[0214] ③NAC group: ip D-Gal 500mg / kg and LPS 20μg / kg+NAC 155mg / kg

[0215] ④F573H group ip D-Gal 500mg / kg and LPS 20μg / kg+F573 5.0mg / kg

[0216] ⑤F573M group ip D-Gal 500mg / kg and LPS 20μg / kg+F573 2.5mg / kg

[0217] ⑥F573L group ip D-Gal 500mg / kg and LPS 20μg / kg+F573 1.25mg / kg

[0218] The experimental results showed that after the rats were treated with D-GalN / LPS, typical fulminant hepatic failure appeared, the levels of serum ALT, AST and T Bil increased sharply and significantly, and the cell apoptosis was significant, and the model was established.

[0219]...

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Abstract

The invention provides a dipeptide derivative and an application of the dipeptide derivative. Particularly, the invention provides an N-substituted 2(1H) dipeptide derivative or a pharmaceutically acceptable salt of the N-substituted 2(1H) dipeptide derivative and a pharmaceutical composition containing the compound. The compound is capable of effectively treating various hepatic failures such as acute hepatic failure and chronic-on-acute hepatic failure.

Description

technical field [0001] The invention relates to the field of medicines, more specifically to a dipeptide derivative for treating liver failure and its application in the preparation of medicines for treating liver failure. Background technique [0002] Liver failure refers to severe liver damage caused by various factors, leading to serious impairment or decompensation of the synthesis, detoxification, excretion and biotransformation of the liver itself. A group of symptoms manifested by dehydration, etc. Liver failure has a high mortality rate. [0003] In 2006, China's "Guidelines for the Diagnosis and Treatment of Liver Failure" divided liver failure into the following four categories: [0004] (a) Acute liver failure refers to acute onset, liver failure characterized by grade II or higher hepatic encephalopathy within 2 weeks; [0005] (b) Subacute liver failure refers to liver failure with rapid onset and clinical manifestations of liver failure within 15 days to 26 ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K5/072C07K5/065A61K38/05A61P1/16
Inventor 罗楹
Owner BEIJING CONTINENT PHARM CO LTD
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