Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

A stable Apremilast crystal form II free of solvates and a preparing method thereof

A crystal form and solvent technology, applied in the field of medicinal chemistry, can solve problems such as disadvantages and achieve the effect of excellent bioavailability

Active Publication Date: 2015-07-08
UTOPHARM SHANGHAI
View PDF5 Cites 12 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, Celgene's commercial product Otezla is only valid for one year, which is extremely unfavorable for commercialized products

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A stable Apremilast crystal form II free of solvates and a preparing method thereof
  • A stable Apremilast crystal form II free of solvates and a preparing method thereof
  • A stable Apremilast crystal form II free of solvates and a preparing method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0126] Embodiment 1: Apremilast crystal form II

[0127] Add apremilast (10.0g) and 35ml of acetone into a three-necked flask, heat to dissolve, then cool to below 35°C, slowly add 0.5-3.0 times the amount of purified water dropwise, add a small amount of crystal form II as a seed crystal, and stir for 1 hour to After the product was precipitated, continue to add 5 times the amount of purified water (175ml), continue to stir overnight at 15-20°C for about 24 hours, filter, wash with water, and dry at 60°C to obtain about 9.32 grams of apremilast crystal form II. mp: 147.2-149.8°C.

Embodiment 2

[0128] Embodiment 2: Apremilast crystal form II

[0129] Add Apremilast (400.0g) and 1200ml of acetone into a three-necked flask, heat to dissolve, slowly add 0.5-2.0 times the amount of purified water dropwise, add a small amount of crystal form II as a seed crystal, stir for 1 hour until the product precipitates, and then continue to add 2 Double the amount of purified water (2.4L), continue to stir overnight at 10-60°C for about 18 hours, filter, wash with water, and dry at 60°C to obtain about 392.3 grams of apremilast crystal form II, mp: 147.2-150.2°C .

Embodiment 3

[0130] Embodiment 3: Apremilast crystal form B

[0131] Add apremilast (10.0g) and acetone (30ml) into a three-necked flask, heat to dissolve, then slowly add 10ml of purified water under cooling to 30°C, stir under cooling until the product precipitates, stir for 2 hours, continue to slowly add water dropwise (100ml), continue to heat and stir overnight, for about 24 hours, filter, wash with water, and dry at 60°C to obtain about 9.45 grams of apremilast crystal form B, mp: 156.2-157.8°C.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a stable Apremilast (shown as a formula I) crystal form II free of solvates, and a preparing method, pharmaceutical compositions and pharmaceutical uses thereof, and discloses a mixed crystal of the crystal form II and a crystal form B and a preparing method thereof. The crystal form II is confirmed by a melting point, an X-ray powder diffraction pattern (XRPD), an infrared spectrum (IR), a differential thermal analysis graph (DSC) and a thermogravimetric curve (TG). Compared with crystal forms A, B, C, D, E, F and G reported in the present literature, the Apremilast crystal form II is more stable to temperature, light and humidity and is beneficial to long-term storage, a crystallization solvent used is safe and easy to remove, the crystal form II is white or off-white and can be directly used for preparation processing, and the preparing method of the crystal form II is simple in operation, easy to repeat and suitable for industrial production.

Description

technical field [0001] The present invention relates to apremilast crystal form II, in particular to a phosphodiesterase 4 (PDE4) small molecule inhibitor apremilast crystal form II, a pharmaceutical composition and a preparation method thereof, and the use thereof Use of the crystal form for treating various diseases or conditions. The invention belongs to the field of medicinal chemistry. Background technique [0002] As we all know, different crystallization solvents or different crystallization methods, such as crystallization temperature, cooling rate, stirring or standing, etc., will produce different crystal forms, and different crystal forms have different stability and solubility, sometimes even in vivo bioavailability varies. Therefore, it is necessary to find a crystal form with high purity and thermodynamic stability in drug development, and the method is easy to reproduce and suitable for industrial large-scale preparation. In addition, X-ray powder diffracti...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/48A61K31/4035A61P17/06A61P19/02A61P19/08A61P29/00A61P17/00A61P1/02A61P1/04A61P25/16A61P17/04A61P1/16A61P27/02A61P27/04A61P25/24A61P13/10A61P15/02A61P13/08A61P7/00A61P9/00A61P21/00A61P15/00A61P25/00A61P11/00A61P31/18A61P37/06A61P37/02A61P19/10A61P1/00A61P35/00A61P35/02
CPCC07D209/48C07B2200/13A61K31/4035A61P1/00A61P1/02A61P1/04A61P1/16A61P11/00A61P13/08A61P13/10A61P15/00A61P15/02A61P17/00A61P17/04A61P17/06A61P19/02A61P19/08A61P19/10A61P21/00A61P25/00A61P25/04A61P25/16A61P25/24A61P27/00A61P27/02A61P27/04A61P29/00A61P31/04A61P31/18A61P35/00A61P35/02A61P37/00A61P37/02A61P37/06A61P39/00A61P7/00A61P9/00C07D209/46G01N23/2005G01N25/4866G01N2021/3595
Inventor 罗军芝年静高思原
Owner UTOPHARM SHANGHAI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com