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Medicinal composition for prevention or treatment of parasitic protozoan infection

A technology of drugs and compounds, which is applied in the field of pharmaceutical compositions for the prevention or treatment of protozoan infectious diseases, and can solve the problems of not knowing the causal relationship and the difficulty of compound structures, etc.

Active Publication Date: 2012-01-25
FUJIFILM CORP +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

), but little is known about the causal relationship between parasitic infections and the effects of drugs, and in this situation, it is extremely difficult to discover the structure of compounds that are effective against protozoan infections

Method used

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  • Medicinal composition for prevention or treatment of parasitic protozoan infection
  • Medicinal composition for prevention or treatment of parasitic protozoan infection
  • Medicinal composition for prevention or treatment of parasitic protozoan infection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] 1-1. Cultivation of Drug-Susceptible Tropical Fever Malaria Protozoa

[0064] In this example, a protozoan of Plasmodium falciparum F CR-3 strain was used. The medium used in the experiment was filter-sterilized RPMI-1640 medium, the pH of which was adjusted to 7.4, and human serum was added to a final concentration of 10%. The cultivation of malaria protozoa in O 2 Concentration 5%, CO 2 Concentration 5%, N 2 The concentration is 90%, and the temperature is 36.5°C.

[0065] 1-2. Drug-sensitive Tropical Fever Malaria Protozoan Proliferation Inhibition Screening Test

[0066] The cultured malarial protozoa-infected erythrocytes were collected by centrifugation, washed with serum-containing medium, and then non-infected erythrocytes were added. The initial infection rate was 0.3%. The hematocrit value at this time was 3%. The compound of the present invention used in the test and the positive drug (chloroquine, quinine) were dissolved in dimethyl sulfoxide (DMSO) as...

Embodiment 2

[0087] 2-1. Cultivation of chloroquine-resistant tropical malaria protozoa

[0088] A protozoa of Plasmodium falciparum K1 strain was used in this example. The culture medium used in the experiment is a culture medium formed by adding human serum at a final concentration of 5% to the filter-sterilized RPMI-1640 medium. The cultivation of malaria protozoa in O 2 Concentration 3%, CO 2 Concentration 4%, N 2 The concentration was 93%, and the temperature was 37°C.

[0089] 2-2. Chloroquine-resistant Tropical Fever Malaria Protozoan Proliferation Inhibition Screening Test

[0090] The compound of the present invention used in the test-positive object drug (chloroquine) was dissolved in DMSO to prepare a test solution with a predetermined concentration. The cultured malarial protozoa-infected erythrocytes were collected by centrifugation and diluted with non-infected erythrocytes. The initial infection rate was 0.15%. The hematocrit value at this time was 2.5%. Add 200 μL of...

Embodiment 3

[0111] 3-1. Culture of African trypanosomiasis protozoa

[0112] In this example, the bloodstream-dwelling trypanomastigotes of the protozoa of Trypanosoma brucei rhodensiense (STIB 900 strain) were used. The medium used in the experiment was filter-sterilized MEM medium supplemented with 25mM N-2-hydroxyethylpiperazine-2-ethanesulfonic acid (HEPES), 1g / L glucose, 1% MEM non- Essential amino acids, 0.2mM 2-mercaptoethanol, 2mM sodium pyruvate, 0.1mM hypoxanthine, cold and 15% heat-treated horse serum prepared medium. Protozoa were cultured in CO 2 Concentration of 5% in the air, at a temperature of 37 degrees.

[0113] 3-2. African trypanosomiasis protozoan proliferation inhibition screening test

[0114] The compound of the present invention used in the test and the positive drug (Melarsoprol (Melarsoprol)) were dissolved in dimethyl sulfoxide (DMSO) to prepare a test solution with a predetermined concentration. In the wells of the 96-well culture plate, the number of pro...

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Abstract

The invention provides a medicinal composition for the prevention or treatment of parasitic protozoan infection which has highly selective toxicity to parasitic protozoan infection and produces a high preventive or therapeutic effect thereon. The medicinal composition for the prevention or treatment of parasitic protozoan infection is characterized by containing a compound represented by the following general formula (1) as an active ingredient. [Chemical formula 1] (In the formula, R represents alkyl, aryl, or a heterocyclic group; A and B each independently represents a 5- or 6-membered ring containing at least one heteroatom or a fused ring comprising the 5- or 6-membered ring and one or more 3- to 8-membered rings fused therewith; Y represents S, O, Se, or -NR<1>- (R<1> represents alkyl, aryl or a heterocyclic group); L<1>, L<2>, L<3>, L<4>, and L<5> each independently represents methine; Q represents a physiologically acceptable anion; k is an integer of 0-2 which is necessary for making the charge of the whole molecule zero; and p and q each is 0-3, provided that the sum of p and q is an integer of 1-6.

Description

technical field [0001] The present invention relates to a pharmaceutical composition useful for the prevention or treatment of parasitic protozoan infectious diseases. Background technique [0002] Known so far, especially in areas centered on tropical and subtropical regions, there are many parasitic protozoan infectious diseases, for example, malaria, leishmaniasis, African trypanosomiasis (African sleeping sickness), American cone Worm disease (Chagas (Chagas)), lymphatic filariasis, babesiosis, etc. Among them, infectious diseases can be divided into infectious diseases that only infect humans, and zoonotic infectious diseases that also infect domestic animals and small animals. No matter which infectious disease causes serious economic and social damage. Currently, in these diseases, there are problems such as the absence of drugs with sufficient therapeutic effects, the emergence and spread of protozoa resistant to therapeutic drugs, and side effects of therapeutic dr...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/428A61K31/427A61P33/02A61P33/06C07D277/64C07D277/84C07D417/14A61K31/4439A61K31/4709
CPCC07D417/14A61K31/4439A61K31/4709A61K31/427C07D277/84C07D277/64A61K31/428A61P33/02A61P33/06Y02A50/30
Inventor 井原正隆高须清诚普多霍姆·卡尼塔北口博司川上雅之佐藤幸藏
Owner FUJIFILM CORP
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