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Antitubercular compound drug with no/low side effect

A technology for tuberculosis and side effects, applied in the field of compound anti-tuberculosis drugs, can solve problems such as non-good design, achieve obvious inhibitory activity and reduce liver toxicity and side effects

Inactive Publication Date: 2016-08-10
INT EDUCATION FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] It can be seen that the above-mentioned existing anti-tuberculosis drug isonicotinamide (isoniazid) still has many deficiencies, is not a good design, and urgently needs to be improved.

Method used

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  • Antitubercular compound drug with no/low side effect
  • Antitubercular compound drug with no/low side effect
  • Antitubercular compound drug with no/low side effect

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1 Animal experiment of isonicotinamide (INH) combined with CYP2E1 inhibitor disulfiram (DSF) and / or nitrophenol phosphate diester (BNPP)

[0042] 1. Materials and methods

[0043] 1. Test material

[0044] All organic solvents were HPLC grade purchased from Tedia Co., Ltd. (Fairfield, OH, USA), INH, BNPP, DSF and corn oil were purchased from Sigma Chemical Company (St.Louis, MO USA), 8-iso-PGF 2α and radiographically calibrated 8-iso-PGF 2α -d 4 It was obtained from Cayman Chemical Company (Ann Arbor, MI, USA), and the galactose injection solution was prepared by Nanguang Chemical Pharmaceutical Co., Ltd. by dissolving 400 grams of galactose (Sigma) in 1 liter of an appropriate buffer solution system and isotonic saline. Class distilled water for injection use.

[0045] 2. Test animals

[0046] Male SD (Sprague-Dawley) rats with a body weight of 320-350 grams were purchased from the National Laboratory Animal Center (Taiwan). The animal experiments were car...

Embodiment 2

[0088] Example 2 Screening of Cytochrome P450 2E1 (CYP2E1) Inhibitors-

[0089] cDNA synthesis of microsomal cytochrome P450 2E1.

[0090] 1. Materials and methods

[0091] 1. Test material

[0092] This example uses the screening kit of cytochrome P450 2E1 (CYP2E1) inhibitors (CYP2E1 High Throughput Inhibitor Screening Kit, BD Bioscience, USA) to conduct cytochrome P450 2E1 (CYP2E1) Screening of inhibitors; the principle of action of the screening kit of CYP2E1 inhibitors is as follows: adding cytochrome P450 2E1 (CYP2E1) and its fluorescent substrate MFC (7-Methoxy-4-trifluoromethyl coumarin) to the environment After the test sample has acted, detect the generation of CYP2E1 metabolite standard HFC (7-Hydroxy-4-trifluoromethyl coumarin), and calculate the CYP 2E1 inhibition rate of the test sample based on the HFC generation of the control group (control) .

[0093] Each test sample was dissolved in acetonitrile (acentoitrile), and the inhibition rate of CYP2E1 was teste...

Embodiment 3

[0140] Example 3 Screening of Cytochrome P450 2E1 (CYP2E1) Inhibitors - Human Liver Microsomal Cytochrome P450 2E1

[0141] 1. Materials and methods

[0142] 1. Test material

[0143]In this example, microsomes prepared from human liver were used to screen cytochrome P450 2E1 (CYP2E1) inhibitors against cytochrome P450 2E1 (CYP2E1), 39 kinds of traditional Chinese medicines and 10 kinds of excipients, so as to screen out the inhibitors of cytochrome P450 2E1 (CYP2E1) An effective inhibitor of cytochrome P450 2E1 (CYP2E1) in the liver; the screening principle of the CYP2E1 inhibitor is as follows: the cytochrome P450 2E1 (CYP2E1) in microsomes prepared from human liver reacts with its substrate Chlorzoxazone, and after adding the test sample, Then detect the production of CYP2E1 metabolite standard 6-OH-CZX (6-Hydroxy-Chlorzoxazone), and calculate the CYP 2E1 inhibition rate of the test sample based on the production of 6-OH-CZX in the control group (control) .

[0144] Each...

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Abstract

The invention provides an antitubercular compound drug with no / low side effect. The antitubercular compound drug a pharmaceutically effective dosage of one or more drugs selected from a group consisting of isoniazid, rifamycin, propylthioisonicotinamide and acetamide alcohol, and a pharmaceutically effective dosage of a substance capable of reducing side effect of the antitubercular drug.

Description

technical field [0001] The invention relates to a compound anti-tuberculosis medicine with no / low side effects. Background technique [0002] According to World Health Organization (WHO) estimates, about one-third of the world's population is infected with tuberculosis, and there are about 8 million new cases every year; and the number of newly registered tuberculosis patients in Taiwan has also been rising in recent years, with every ten More than 60 people per 10,000 people are infected with tuberculosis, but only about three-quarters of them receive complete treatment; according to statistics from the Department of Health, at least 4.2 people die of tuberculosis every day in Taiwan; with so many patients receiving tuberculosis drug treatment Among them, the most common clinical side effects of drugs are hepatotoxicity and neurological lesions (such as: auditory nerve and optic neuropathy), among which hepatotoxicity is the most common. In addition, Taiwan is an area wher...

Claims

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Application Information

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IPC IPC(8): A61K31/4965A61K31/496A61K31/4409A61K31/05A61K31/133A61K31/16A61K31/353A61K31/352A61K31/12A61K31/192A61K31/7034A61K31/11A61K31/01A61K31/015A61K31/7048A61K31/37A61P31/06
CPCA61K31/4965A61K31/01A61K31/015A61K31/05A61K31/11A61K31/12A61K31/133A61K31/16A61K31/192A61K31/352A61K31/353A61K31/37A61K31/4409A61K31/496A61K31/7034A61K31/7048A61K2300/00
Inventor 胡幼圃杨东和熊正辉张温良石东原何欣恬
Owner INT EDUCATION FOUND
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