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Iboga alkaloid or its pharmaceutically acceptable salt, preparation method and application, iboga alkaloid pharmaceutical composition and application

A technology of alkaloids and compositions, which is applied in the pharmaceutical composition of Iboga alkaloids and its application fields, can solve the problems of heavy economic burden on patients and society, the increase of drug resistance of Candida albicans, etc., and achieve strong drug resistance reversal activity, The effect of low cost and wide source of raw materials

Active Publication Date: 2020-08-07
KUNMING INST OF BOTANY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Fluconazole, as the first-line antimicrobial drug currently used to treat deep fungus, has achieved good clinical therapeutic effects, but in recent years, with the wide application of fluconazole, the drug resistance of Candida albicans is increasing year by year, causing patients and a heavy economic burden on society

Method used

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  • Iboga alkaloid or its pharmaceutically acceptable salt, preparation method and application, iboga alkaloid pharmaceutical composition and application
  • Iboga alkaloid or its pharmaceutically acceptable salt, preparation method and application, iboga alkaloid pharmaceutical composition and application
  • Iboga alkaloid or its pharmaceutically acceptable salt, preparation method and application, iboga alkaloid pharmaceutical composition and application

Examples

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preparation example Construction

[0052] The present invention provides the preparation method of iboga alkaloid described in the above technical scheme, comprising the following steps:

[0053] mixing the dog's tooth flower and the extractant, extracting and concentrating to obtain the extract;

[0054] Adjusting the pH value to acidic, the first extraction, adjusting the pH value to alkaline, the second extraction and purifying the extract in sequence to obtain the iboga alkaloid;

[0055]The purification includes the first silica gel column chromatography and the first reverse-phase chromatographic separation carried out in sequence to obtain several sections of eluent, and the several sections of eluent are respectively subjected to the second silica gel column chromatography, the second reverse-phase Chromatographic separation and SephadexLH-20 separation;

[0056] The eluent used in the first silica gel column chromatography is a mixed solution of petroleum ether and acetone, and the volume ratio of the...

Embodiment 1

[0091] 10kg of dried branches and leaves of Bermudagrass were heated to 68°C with 50L of methanol and refluxed for 3 times, each time for 3h, the extracts were combined, and the methanol was recovered by distillation under reduced pressure to obtain the extract.

[0092] The extract was mixed with 2000mL of 5% hydrochloric acid aqueous solution, and the pH value was adjusted to 2, respectively extracted 3 times with 2000mL petroleum ether and 2000mL ethyl acetate, then the pH value was adjusted to 9 with saturated sodium carbonate solution, and the pH value was adjusted with chloroform Extraction gave total base (70 g).

[0093] The total alkali is eluted with petroleum ether / acetone gradient (petroleum ether / acetone=30:1~10:1, v / v), and then separated by reverse phase chromatography C-18 (methanol / water=20:80~90 :10, v / v), get FrA, FrB and FrC three parts.

[0094] The FrA part is sequentially separated by silica gel column chromatography, reverse phase chromatography C-18 a...

Embodiment 2

[0119] Mix the irbola alkaloid prepared in Example 1 and water for injection evenly, perform fine filtration, potting and sterilization in sequence to obtain the erboga alkaloid injection.

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Abstract

The invention provides Iboga alkaloid or pharmaceutically acceptable salt thereof, a preparation method and application thereof, an iboga alkaloid pharmaceutical composition and application thereof, and belongs to the technical field of medicines. The iboga alkaloid provided by the invention has no obvious inhibitory activity on a candida albicans fluconazole drug-resistant strain; however, when fluconazole and iboga alkaloid jointly act on the candida albicans fluconazole drug-resistant strain, the drug resistance of the candida albicans fluconazole drug-resistant strain is improved; the inhibition rate of the iboga alkaloid on the candida albicans fluconazole drug-resistant strain is as high as 99.7%, so that the iboga alkaloid provided by the invention has very strong drug-resistant reversal activity on the candida albicans fluconazole drug-resistant strain, and is a candidate drug which has development potential and can reverse the drug resistance of the candida albicans fluconazole drug-resistant strain.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to iboga alkaloid or a pharmaceutically acceptable salt thereof, a preparation method and application, and an iboga alkaloid pharmaceutical composition and application. Background technique [0002] Candida albicans is the main pathogenic fungus of nosocomial infection. With the widespread use of antifungal drugs, the cases of deep fungi caused by Candida albicans infection are increasing year by year. Fluconazole, as the first-line antimicrobial drug currently used to treat deep fungus, has achieved good clinical therapeutic effects, but in recent years, with the wide application of fluconazole, the drug resistance of Candida albicans is increasing year by year, causing patients and a heavy economic burden on society. In view of the complexity of the fluconazole resistance mechanism of Candida albicans and the seriousness of drug resistance forms, it is urgent to develop antifun...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D471/18A61K31/55A61P31/10
CPCA61P31/10C07D471/18
Inventor 张于郝小江郭伶俐白雪
Owner KUNMING INST OF BOTANY - CHINESE ACAD OF SCI
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