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Pharmaceutical composition containing liriodendron tulipifera l. extract for treating chronic myelogenous leukemia

A technology of myeloid leukemia and composition, applied in the field of T315I enzyme variant

Inactive Publication Date: 2016-02-24
CHO DANG PHARM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the emergence of the T315I enzyme variant expressed by the mutated gene of BCR-ABL, such second generation therapeutics are no longer able to show sufficient efficacy

Method used

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  • Pharmaceutical composition containing liriodendron tulipifera l. extract for treating chronic myelogenous leukemia
  • Pharmaceutical composition containing liriodendron tulipifera l. extract for treating chronic myelogenous leukemia
  • Pharmaceutical composition containing liriodendron tulipifera l. extract for treating chronic myelogenous leukemia

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0059] (Preparation Example 1) Preparation of the extract (CD-200) from the bark of Liriodendron tulipifera

[0060] 1. Solvent extraction step

[0061] 200 g of chopped and dried bark of Liriodendron tulipifera (3-5 years old) was stirred and extracted with 2000 ml of ethyl acetate for 24 hours at room temperature. The primary extract was obtained after concentration and filtration of the extracted mixture under reduced pressure. The resulting primary extract was further mixed and extracted with 500 ml butanol for 2-4 hours at room temperature. Then, the butanol soluble material was removed by separating and removing the butanol layer. After concentrating the remaining mixture, 12.54 g of crude extract was finally obtained.

[0062] 2. Purification steps

[0063] After 12.54 g of the obtained crude extract was dissolved in 200 ml of 70% ethanol, 200 ml of n-hexane was added to the crude extract mixture and stirred. After separating and removing the n-hexane layer, a 70% ...

preparation example 2

[0064] (Preparation Example 2) Preparation and separation of epituliprolactone fraction (CD-EPT) as the main component of CD-200 from the bark of Liriodendron tulipifera

[0065] The high performance liquid chromatography (HPLC) Alliancee 2695 system of WATERS was used to separate the epituliprolactone fraction from the extract CD-200 from the bark of Liriodendron tulipifera. The conditions of HPLC analysis were as follows: using a reversed-phase column Kromasil C18, loading 5 mg / ml of the sample, and measuring the amount of the eluate with a UV wavelength of 215 nm (flow rate: 1.0 ml / min). In addition, mobile phase (water and methanol) gradient conditions were employed. Finally, the epituliprolactone fraction was isolated from the fraction with retention time = ~31 minutes. This extract was named CD-EPT.

preparation example 3

[0066] (Preparation Example 3) Isolation and Identification of Epituliprolactone (CD-EPT)

[0067] After loading and passing both the samples of the above fractions and the epi-lipidolide standard through the HPLC column, the epi-lipidolactone in the obtained fractions was identified by comparing the retention times. Then, since the retention time of both the obtained site and epi-lipidolide was measured to be the same, it was confirmed that the component of the obtained site was mainly composed of epi-lipidolactone. In addition, the specific rotation of epituliprolactone was measured. The measured value of epituliprolactone from CD-200 ([α]D=+74) was almost in agreement with the reported value of epituliprolactone ([α]D=+76). Therefore, the presence of epituliprolactone was confirmed by stereochemistry.

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Abstract

The present invention relates to a pharmaceutical composition containing, as an active ingredient, a Liriodendron tulipifera L. bark extract for treating chronic myelogneous leukemia. More specifically, the present invention relates to the pharmaceutical composition, containing, as the active ingredient, the Liriodendron tulipifera L. bark extract useful in selectively inhibiting mutant enzyme T315I from a mutation of a BCR-ABL fusion gene that causes chronic myelogenous leukemia, and to a use of epi-Tulipinolide which is an active ingredient of the composition.

Description

technical field [0001] The present invention relates to a pharmaceutical composition for the treatment of chronic myelogenous leukemia, which contains an extract from the bark of Liriodendron tulipifera as an active ingredient. Specifically, the present invention relates to a pharmaceutical composition containing an extract from the bark of Liriodendron tulipifera as an active ingredient and an extract from the bark of Liriodendron tulipifera (containing epi-tulipinolide As an active ingredient), the pharmaceutical composition is used to selectively inhibit the T315I enzyme variant produced by the BCR-ABL fusion gene. Background technique [0002] Liriodendrontulipifera L., Yellow-poplar is a deciduous broad-leaved tree belonging to Magnoliaceae. The bark of Liriodendron tulipifera is known to contain alkaloids, sesquiterpenes and / or lignans. [0003] In addition, the extract of Liriodendron tulipifera contains sesquiterpene lactone compounds, including coynelide, tulipyl ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K36/896A61P35/02
CPCA61K31/365A61K36/57A61P35/02A61P43/00A61K36/896
Inventor 金基运俞慧东洪淳善金水晶李炫昇方正焕姜秀珍
Owner CHO DANG PHARM
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