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Hydrate of echinocandin B mother nucleus or salt thereof, preparation method and application thereof

A technology of echinocandin and hydrate, which is applied in the field of hydrate with echinocandin B core or its salt and its preparation, can solve the problems of poor stability of echinocandin B core and achieve It is conducive to long-term preservation, reduces production costs, and facilitates industrial production

Active Publication Date: 2016-06-15
JIANGSU SENRAN CHEM +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

As mentioned above, when the moisture content of echinocandin B nucleus hydrochloride is lower than 7.0%, the stability of echinocandin B nucleus becomes significantly worse

Method used

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  • Hydrate of echinocandin B mother nucleus or salt thereof, preparation method and application thereof
  • Hydrate of echinocandin B mother nucleus or salt thereof, preparation method and application thereof
  • Hydrate of echinocandin B mother nucleus or salt thereof, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0068] The preparation of embodiment 1 echinocandin B parent nucleus crude product

[0069] With reference to the method described in US4293489, the crude product of the echinocandin B parent nucleus represented by formula I was prepared.

Embodiment 2

[0070] Example 2 Preparation of hydrates A, B, C, D, E, F of echinocandin B parent nucleus hydrochloride

[0071]

[0072] At 40°C, 10.0 g of the solid powder of the compound represented by formula I prepared in Example 1 was dissolved in 30 ml of water and stirred for 30 minutes to completely dissolve the compound represented by formula I. The pH was adjusted to 3.5 with hydrochloric acid, the solution was cooled to 10°C to 20°C, stirred for 20 hours, and filtered to obtain the hydrate of the compound represented by formula I-1. The hydrate of the compound represented by formula I-1 is vacuum dried at 20°C to 25°C. After drying for 1 hour, 1.0 g of hydrate was taken and named as hydrate A of the compound represented by formula I-1, and the mass percentage content of water in hydrate A was measured to be 28.9%. The remaining sample was continued to be dried for 1 hour, and 1.0 g of the sample was sampled and named as hydrate B of the compound represented by formula I-1. ...

Embodiment 3

[0081] Example 3 Preparation of hydrates G, H, I of echinocandin B parent nucleus hydrochloride (influence of pH value)

[0082] Take 8.75 g of the crude echinocandin B (compound I) obtained in Example 1, add 30 ml of water and 5 ml of methanol, stir to dissolve at 25-35°C, adjust the pH to 2.2 with hydrochloric acid, and stir to dissolve at room temperature. The solution was cooled to -5 to 5° C., stirred for 10 hours, and filtered to obtain a hydrate of the compound represented by formula I-1. The hydrate of the compound represented by formula I-1 is vacuum dried at 20°C to 25°C. After drying for 1 hour, 1.0 g of hydrate was taken and named as hydrate G of the compound represented by formula I-1, and the mass percentage content of water in G was measured to be 34.8%. The remaining sample was continued to be dried for 3 hours, and 1.0 g of hydrate was taken and named as hydrate H of the compound represented by formula I-1, and the mass percentage content of water in H was ...

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PUM

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Abstract

The invention provides a hydrate of echinocandin B mother nucleus or salt thereof. When mass percentage of water in the hydrate is 7.0-31.0%, the hydrate has excellent stability. In addition, the invention also discloses a preparation method and an application of the hydrate of echinocandin B mother nucleus or the salt thereof.

Description

technical field [0001] The present invention relates to a pharmaceutical composition, more specifically to a hydrate having an echinocandin B nucleus or a salt thereof with good stability, a preparation method and application thereof. Background technique [0002] In recent years, due to the extensive use of immunosuppressants caused by organ transplantation, the application of chemotherapy and more aggressive medical methods, the spread of AIDS, and the abuse of broad-spectrum antibacterial drugs, the number of people with suppressed immune systems has continued to increase. The incidence of infection was significantly increased. Fungal infection has become the main cause of high morbidity and mortality in immunocompromised patients. The incidence of fungal infections has increased significantly over the past 20 years. High-risk groups for fungal infections include critically ill patients, surgical patients, and those with HIV infection, leukemia, and other neoplastic dis...

Claims

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Application Information

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IPC IPC(8): C07K7/56C12P17/10
Inventor 张有理叶键张成伟岳崇斌郭明袁建栋
Owner JIANGSU SENRAN CHEM
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