Check patentability & draft patents in minutes with Patsnap Eureka AI!

Novel crystal form of ledipasvir and preparation method thereof

一种晶型、溶剂化物的技术，应用在药物化学领域，能够解决无定形、不能很好地满足实际应用需求等问题

Active Publication Date: 2015-10-07
SHANGHAI FOREFRONT PHARMA CO LTD
View PDF4 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These two crystal forms show better crystallization and purification effects, and the light stability is improved compared with the amorphous form, but their degradation is still as high as 6.3% after 1.2 million lux hours of light, which cannot well meet the practical application need

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
  • Novel crystal form of ledipasvir and preparation method thereof
  • Novel crystal form of ledipasvir and preparation method thereof
  • Novel crystal form of ledipasvir and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0154] The present invention also provides a kind of preparation method of described solvate, described method comprises the steps:

[0155] 1) Provide ledipasvir amorphous powder, the mixed solvent of component A and component B;

[0156] 2) mixing the ledipasvir amorphous powder and the mixed solvent, and crystallizing to obtain the solvate.

[0157] In another preferred example, the HPLC purity of the amorphous powder of ledipasvir is 85-98%, preferably 90-98%, more preferably 95-98%.

[0158] In the present invention, the volume ratio of component A and component B in the mixed solvent is not particularly limited, and can be adjusted in a wide range according to actual needs.

[0159] Typically, the volume ratio of component A to component B in the mixed solvent is 1:1-5, preferably 1:1-4, more preferably 1:1-3.

[0160] In the present invention, the addition ratio of the ledipasvir amorphous powder and the mixed solvent is not particularly limited, and can be adjusted i...

Embodiment 1

[0212] Embodiment 1 Preparation of ledipasvir crystal form A

[0213] Weigh 100 mg of ledipasvir amorphous powder into a 1.5 ml centrifuge tube, add 0.25 ml of acetonitrile (ACN) and methyl tert-butyl ether (MTBE) mixed solvent (volume ratio 1:3), and sonicate until dissolved. Place this solution at room temperature under airtight condition. After 3 days, a solid precipitate was observed, which was confirmed to be crystalline by polarizing microscopy.

[0214] Place the centrifuge tube in a centrifuge (Eppendorf mini spin) at 12,000 rpm for 5 minutes, remove the supernatant, and dry the separated solid at room temperature for 1 hour to obtain Form A (LDV-acetonitrile-MTBE ternary solvates).

[0215] result

[0216] The product obtained in Example 1 was detected by XRD, DSC and TGA.

[0217] figure 1 It is the XRD figure of embodiment 1 crystal form A of the present invention. from figure 1 It can be seen that the main diffraction peaks and relative intensities of crysta...

Embodiment 2

[0225] Embodiment 2 Preparation of ledipasvir crystal form B

[0226]Weigh 40 mg of ledipasvir amorphous powder into a 1.5 ml centrifuge tube, add 0.2 ml of a mixed solvent of acetone (Acetone) and MTBE (volume ratio 1:2) to form a suspension. The suspension was left at room temperature and shaken for 3 days. After 3 days, a solid precipitate was observed, which was confirmed to be crystalline by polarizing microscopy.

[0227] Place the centrifuge tube in a centrifuge at 12,000 rpm for 5 minutes, remove the supernatant, and dry the separated solid at room temperature for 1 hour to obtain Form B (LDV-acetone-MTBE ternary solvate).

[0228] result

[0229] Figure 4 It is the XRD figure of embodiment 2 of the present invention Form B. from Figure 4 It can be seen that the main diffraction peaks and relative intensities of the crystal form B obtained in Example 2 are shown in Table 2.

[0230] Table 2. XRD data of ledipasvir crystal form B

[0231] 2θ position [...

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 relates to a novel crystal form of ledipasvir and a preparation method thereof, and particularly discloses a ledipasvir solvate. The solvate is a solvate formed by ledipasvir (LDV) and a solvent A and / or a solvent B, wherein the solvent A is acetonitrile or acetone; the solvent B is methyl tert-butyl ether (MTBE). The invention also discloses a preparation method and an application of the solvate. The solvate has high purity, excellent crystallization performance and better optical stability. The preparation method is simple and stable in process. The solvate can greatly improve the quality control and industrial application of medicine containing ledipasvir.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a new crystal form of ledipasvir and a preparation method thereof. Background technique [0002] Ledipasvir (LDV) (see formula I for structural formula) is a hepatitis C treatment drug developed by Gilead. The FDA has granted breakthrough therapy designation for LDV / SOF (Sofosbuvir) fixed-dose combination drug. The combination therapy is expected to be effective in as little as 8 weeks. Cure patients with genotype 1 HCV within 10 minutes without injection of interferon or combination of ribavirin (Ribavirin). [0003] [0004] Crystal form is a term used to describe the crystalline state of a compound, covering polymorphs, solvates, salt forms, co-crystals, etc. The crystal form has a profound impact on the physical and chemical properties of the compound, such as stability, solubility, powder properties, etc. At the same time, the crystallization process is also an import...

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): C07D403/14A61K31/4184A61P31/14
CPCC07D403/14A61K31/4439A61P31/14C07B2200/13
Inventor 李巍任毅黄成军朱燕燕傅绍军富刚魏哲文
Owner SHANGHAI FOREFRONT PHARMA CO LTD
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com