Arginase inhibitor as well as pharmaceutical composition and application thereof

An arginase and inhibitor technology, applied in the field of its pharmaceutical composition and arginase inhibitor, can solve the problems of poor activity, high cost of drug preparation and medication, insufficient treatment convenience, etc., and achieve good safety It has the advantages of high stability, easy promotion and production, and low preparation cost.

Pending Publication Date: 2022-04-12
QINGHAI UNIVERSITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Based on the problems existing in the prior art, it is necessary to provide a new type of arginine derived from natural products for the problems of poor activity of current arginase inhibitors, high cost of drug preparation and medication, and insufficient treatment convenience. acidase inhibitor

Method used

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  • Arginase inhibitor as well as pharmaceutical composition and application thereof
  • Arginase inhibitor as well as pharmaceutical composition and application thereof
  • Arginase inhibitor as well as pharmaceutical composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] The inhibitory activity assay of embodiment 1 arginase inhibitor to arginase

[0037] (1) Draw a urea standard curve: Accurately weigh 10 mg of urea, and prepare 0.1, 0.2, 0.4, 0.8, and 1.2 mg / mL serial concentration solutions with 50 mM Tris HCl; take 50 μL of urea solutions with different concentrations, and add 43 μL of 50 mM Tris HCl respectively , 75μL 10mmol / L MnCl 2 (50mM Tris·HCl preparation), 50μL arginase substrate (0.5mol / L L-arginine, pH9.7), 200μL acid solution (H 2 SO 4 :H 3 PO 4 :H 2O, 1:3:7), 25 μL of 9% 2-isonitrosopropiophenone (prepared in absolute ethanol), heated at 100°C for 45min, and then placed the sample in the dark at room temperature for 10min, and used an automatic microplate reader to The analytical system measures absorbance at 550 nm. The standard curve was obtained by taking the concentration of urea solution as the abscissa and the absorbance value as the ordinate.

[0038] (2) Take 2 mg of arginase, prepare it to 2 mg / mL with 50...

Embodiment 2

[0045] Example 2 Intervention of Arginase Inhibitor Vanillic Acid on Rat Pulmonary Hypertension

[0046] (1) Establish a rat model of pulmonary arterial hypertension by one-time subcutaneous injection of 40 mg / kg monocrotaline, grouped into: control group, MCT model group and drug treatment group rats, from the first day of rat injection of monocrotaline , orally administered three different doses of vanillic acid (25mg / kg / d, 50mg / kg / d and 100mg / kg / d), and 10 experimental rats in each group were fed for 28 days.

[0047] (2) At 28 days, analyze and evaluate its efficacy from body weight, right ventricular pressure, hematological indicators, right heart hypertrophy index, etc. The right ventricular pressure (RVSP) of the rats in each group was measured with a Power Lab physiological recorder and a biological acquisition system using the venous catheter method. After dissection, the rat heart was removed, and the right ventricle was isolated along the interventricular septum, w...

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Abstract

The invention relates to an arginase inhibitor as well as a pharmaceutical composition and application thereof. The arginase inhibitor provided by the invention is selected from any one or more compounds of vanillic acid, eriodictyol, salidroside, roseldine, rhodiolaromone, p-coumaric acid and ethyl gallate, or pharmaceutically acceptable salts, stereoisomers, tautomers, isotopes or prodrugs of the compounds, or pharmaceutically acceptable salts, stereoisomers, tautomers, isotopes or prodrugs of the compounds, or pharmaceutically acceptable salts, stereoisomers, tautomers, isotopes or prodrugs of the compounds. The arginase I, the arginase II and pharmaceutically acceptable auxiliary materials can form a pharmaceutical composition, and the arginase I, the arginase II and pharmaceutically acceptable auxiliary materials can be used for preparing drugs for treating or preventing diseases, symptoms or symptoms related to expression or activity of the arginase I, the arginase II or a combination of the arginase I and the arginase II in individuals. The arginase inhibitor disclosed by the invention has a relatively high inhibition rate on arginase I and arginase II, and is used as a potent and selective arginase inhibitor to reverse immunosuppression and reactivate the anti-cancer immunity of a patient through a single medicament or in a manner of being combined with a therapy for reversing other immunosuppression mechanisms.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to an arginase inhibitor, its pharmaceutical composition and application. Background technique [0002] Arginase is a manganese metalloenzyme that catalyzes the conversion of L-arginine to urea and L-ornithine. There are two isoenzymes of arginase: arginase I and arginase II, arginase I exists in the liver and is the main type of arginase; arginase II exists outside the liver organization, less content. Although these two isoenzymes are encoded by different genes, they are similar in structure, with more than 50% homology of amino acid residues and 100% homology in the key region of catalytic L-arginine metabolism function. [0003] Nitric oxide (NO) is currently recognized as one of the vasodilation factors. The precursor of NO is L-arginine, which is also a substrate of eNOS. When the activity of arginase is enhanced, it can compete with eNOS for its common substrate L-argin...

Claims

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Application Information

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IPC IPC(8): A61K31/192A61K31/352A61K31/7032A61K31/7048A61K45/06A61P9/12A61P11/00A61P15/10A61P9/10A61P13/12A61P19/02A61P11/06A61P37/02A61P17/06A61P1/06A61P1/18A61P37/08A61P25/28A61P9/04A61P19/10A61P17/00A61P35/00A61P35/02
Inventor 李占强苏姗姗芦殿香王珊牛力轩南星梅杨占婷华玉美多
Owner QINGHAI UNIVERSITY
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