A crystal form of pentostatin and its preparation method and application

A pentostatin and crystal form technology, applied in the field of chemical pharmacy, can solve the problems of unfavorable crystal form stability preparation storage stability, poor flowability of needle crystals, affecting preparation operability and the like

Active Publication Date: 2021-04-20
ZHEJIANG HISUN PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Needle crystals generally have poor fluidity, low bulk density, and are difficult to filter and dry, which affects the operability of preparation processing; in addition, needle crystals need to be pulverized before they can be used in solid dosage form pharmaceutical preparations, and pulverization will affect the crystal form. Destruction, which is not conducive to the stability of the crystal form and the storage stability of the preparation

Method used

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  • A crystal form of pentostatin and its preparation method and application
  • A crystal form of pentostatin and its preparation method and application
  • A crystal form of pentostatin and its preparation method and application

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Experimental program
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Effect test

Embodiment 1

[0049] Dissolve 0.2g of crude pentostatin (HPLC purity>95%) in 20mL of methanol, heat up to 50°C, dissolve, filter, add 80ml of methyl acetate under stirring, crystallize at 20°C for 6h, control the stirring speed at 170rpm / min, filtered, and vacuum-dried at 35°C to obtain 0.08g blocky crystals, which were easy to filter and had a purity of 99.7% by HPLC.

[0050] The X-ray powder diffraction and DSC spectrum of this crystal are detailed in Figure 1-2 , which is named pentostatin crystal form I in the present invention.

Embodiment 2

[0052] Dissolve 0.2g of crude pentostatin (HPLC purity>95%) in 10mL of methanol, heat up to 60°C, dissolve, filter, add 60ml of methyl acetate under stirring, crystallize at 25°C for 24h, control the stirring speed at 170rpm / min, filtered, and vacuum-dried at 35°C to obtain 0.11 g blocky crystals, which were easy to filter and had a purity of 99.5% by HPLC. According to X-ray powder diffraction pattern (XRD), it was confirmed to be pentostatin crystal form I.

Embodiment 3

[0054] Dissolve 0.2 g of crude pentostatin (HPLC purity >95%) in 12 mL of methanol, heat up to 55 ° C, dissolve, filter, add 120 ml of methyl acetate while stirring, crystallize at 30 ° C for 8 h, control the stirring speed at 170 rpm / min, filtered, and vacuum-dried at 35°C to obtain 0.14 g blocky crystals, which were easy to filter and had a purity of 99.1% by HPLC. According to X-ray powder diffraction pattern (XRD), it was confirmed to be pentostatin crystal form I.

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Abstract

The present invention relates to a new crystal form I of pentostatin and its preparation method and use. The crystal form I has good solubility and is conducive to improving the intestinal absorption and oral bioavailability of the drug; the crystal form I of the present invention The medicine also has the advantages of high product purity, excellent physical and chemical properties, good chemical stability, and reproducible processing (filtration, drying, and tabletting); the crystallization process of the invention is simple, easy to operate, and less polluting, and can realize industrial production.

Description

technical field [0001] The invention relates to the field of chemical pharmacy. More specifically, the present invention relates to a crystal form of pentostatin, a preparation method of the crystal form and its medical application. [0002] technical background [0003] Pentostatin was isolated from the culture medium of Streptomyces antibioticus by Woo et al. in 1974. It is a strong adenosine deaminase (ADA) inhibitor. Pentostatin has a high affinity with ADA, can bind tightly to ADA, inhibit the activity of ADA, and increase the level of deoxyadenosine triphosphate (dATP) in cells. dATP blocks DNA synthesis by inhibiting ribonucleotide reductase. In addition, pentostatin inhibits RNA synthesis and enhances DNA damage. In February 1998, the U.S. FDA officially approved the marketing of pentostatin for injection (trade name Nipent), which is mainly used for stem cell leukemia (Hairy cell leukemia, HCL), chronic lymphocytic leukemia (CLL) and mycosis fungoides Treatment of...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H19/23C07H1/06A61K31/7056A61P35/00A61P35/02
CPCC07B2200/13C07H1/06C07H19/23
Inventor 李娜张亮陈连蔚应雪肖苏笛
Owner ZHEJIANG HISUN PHARMA CO LTD
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