Pitavastatin calcium compound and preparation method thereof

A technology of pitavastatin calcium and compounds, which is applied in the field of medicine, can solve the problems of low purity of pitavastatin calcium, achieve easy control and industrial production, and improve the effect of clinical adverse reactions

Inactive Publication Date: 2013-12-11
HAINAN MEIDA PHARMA
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] In order to overcome the defects of the above-mentioned prior art, especially the defect of low purity of pitavastatin calcium prepared by the prior art, the invention provides a method for preparing a high-purity pitavastatin calcium compound

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
  • Pitavastatin calcium compound and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036]Get 10g pitavastatin calcium raw material, high-phase liquid chromatography measures content and be 85%, pitavastatin calcium raw material is added in the methyl alcohol-0.1% formic acid aqueous solution that volume ratio is 1: 0.3, is heated to 65-75 ℃, makes Pitavastatin calcium was completely dissolved, filtered, and solid impurities were discarded.

[0037] The above solution was passed through D101 type macroporous adsorption resin, eluted with methanol-0.1% formic acid aqueous solution with a volume ratio of 1:0.3, and the pitavastatin site in the eluate was collected.

[0038] Raise the temperature to 75°C, keep it for 1 hour, adjust the pH to 7 with 0.5M sodium hydroxide, add 10% of the volume of 1M calcium chloride solution while hot, and then add the solution to the solvent volume ratio of 1:2 Tetrahydrofuran. Reduce the temperature to 50-53°C within 1 hour, then reduce the temperature to 22-25°C within 2 hours, and finally reduce the temperature to 5-10°C wit...

Embodiment 2

[0043] Get 10g pitavastatin calcium raw material, high-phase liquid chromatography measures content and be 89%, pitavastatin calcium raw material is added in the methanol-0.1% formic acid aqueous solution that volume ratio is 1: 0.2, is heated to 60-72 ℃, makes Pitavastatin calcium was completely dissolved, filtered, and solid impurities were discarded.

[0044] Pass the above solution through D101 macroporous adsorption resin, elute with methanol-0.1% formic acid aqueous solution with a volume ratio of 1:0.2, and collect pitavastatin in the eluate.

[0045] Raise the temperature to 70°C and keep it for 1 hour, adjust the pH to 6.9 with 0.01M sodium hydroxide, add 10% 0.5M calcium chloride solution while hot, and then add acetone at a volume ratio of solution to solvent of 1:2.5 . Reduce the temperature to 50-52°C within 1 hour, then reduce the temperature to 20-23°C within 3 hours, and finally reduce the temperature to 5-8°C within 10 hours. During this process, crystals con...

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 high-purity pitavastatin calcium compound which has a structural formula shown in the specification, and also relates to a preparation method of the high-purity pitavastatin calcium compound. The method comprises the following steps of: (1) adding a pitavastatin calcium rough product serving as a raw material into methanol-0.1 percent formic acid aqueous solution, dissolving, filtering and abandoning solid impurities; (2) adsorbing obtained solution through macroporous adsorption resin, eluting and collecting eluent; and (3) heating the obtained eluent, concentrating, adjusting the pH value to be close to neutral, adding calcium chloride aqueous solution while the eluent is hot, adding tetrahydrofuran or acetone, reducing temperature in a gradient way, recrystallizing and drying to obtain the purified pitavastatin calcium compound. Through the method provided by the invention, the quality of a preparation product is improved, and the toxic or side effect is reduced; and the method is suitable for industrial large-scale production.

Description

technical field [0001] The invention relates to a high-purity pitavastatin calcium compound and a preparation method thereof, belonging to the technical field of medicine. Background technique [0002] Pitavastatin Calcium (Pitavastatin Calcium), chemical name: +bis {(3R, 5S, 6E)-7-[2-cyclopropyl-4-(fluorophenyl)quinoline-3-phenyl]- 3,5-dihydroxy-6-heptenoic acid ethyl ester} calcium salt, other names: NK-104, itavastatin, Livalo (Liweile), NIK-104, NKS-104, Pitavastatin Calcium (pitavastatin calcium ), molecular formula C 50 h 46 CaF 2 N 2 o 8 , CAS No. 147526-32-7, molecular weight 880.98, structural formula: [0003] [0004] Pitavastatin calcium is the third-generation hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor successfully developed by Japanese companies Kowa and Nissan. HMG-CoA reductase inhibitors have high and specific competitive inhibition of hydroxymethylglutaryl-CoA reductase, inhibit the synthesis of cholesterol (CH) in the liver, and inhi...

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 Patents(China)
IPC IPC(8): C07D215/14
Inventor 廖爱国
Owner HAINAN MEIDA PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap