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

Process for recovery of nalmefene hydrochloride

a technology of nalmefene hydrochloride and recovery process, which is applied in the field of recovery process of nalmefene hydrochloride, can solve the problem that the synthesized precursor of nalmefene is difficult to remove selectively in the recovery process, and achieves the effect of improving the recovery process and improving the recovery process

Active Publication Date: 2014-10-02
H LUNDBECK AS
View PDF0 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0096]Comparison of the data from Example 4 with the data from Examples 1-3 clearly demonstrates that the amount of naltrexone in the end product is efficiently reduced by the process of the invention. Examples 2 and 3 furthermore show that the amount of methyldiphenylphosphine oxide and triphenylphosphineoxide is reduced by extraction with organic solvent.

Problems solved by technology

Particularly naltrexone, the synthetic precursor of nalmefene is difficult to remove selectively in the recovery process since naltrexone has chemical properties very similar to those of nalmefene.

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
  • Process for recovery of nalmefene hydrochloride
  • Process for recovery of nalmefene hydrochloride
  • Process for recovery of nalmefene hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

example 1

Recovery of Nalmefene Hydrochloride from Aqueous Solution

[0092]Nalmefene HCl aqueous mother liquor (400 g); containing about 36 g of “residue of evaporation” with the following composition (% by HPLC area): nalmefene 92.08%, naltrexone 0.49%, methyldiphenylphosphine oxide 0.77%, triphenylphosphineoxide 4.0%; was treated with 0.34 g of sodium bisulfite and concentrated under vacuum distilling 323 g of solvent. The concentrated mixture was cooled down to 0° C. and maintained at this temperature overnight. The solid was filtered and washed with acetone (34 mL) obtaining 21 g of nalmefene HCl. HPLC analysis (% by area): nalmefene 98.92%, naltrexone 0.09%, methyldiphenylphosphine oxide 0.04%, triphenylphosphineoxide 0.16%.

example 2

Recovery of Nalmefene Hydrochloride from Aqueous Solution (Including Extraction with Organic Solvent)

[0093]Nalmefene HCl aqueous mother liquor (400 g); containing about 36 g of “residue of evaporation” with the following composition (% by HPLC area): nalmefene 92.08%, naltrexone 0.49%, methyldiphenylphosphine oxide 0.8%, triphenyiphosphineoxide 4.0%; was extracted with dichloromethane (2*50 mL). The aqueous layer was then concentrated under vacuum obtaining a suspension. Sodium bisulfite (0.3 g) was charged and the mixture was maintained at 60-65° C. for three hours. The suspension was cooled down to 0-5° C. and the solid was filtered and washed with dichloromethane (50 mL) and acetone (about 30 mL) obtaining 28 g of nalmefene HCl. HPLC analysis (% by area): nalmefene 99.36%, naltrexone 0.12%. Methyldiphenylphosphine oxide and triphenylphosphineoxide below detection limit.

example 3

Recovery of Nalmefene Hydrochloride from Aqueous Solution (Including Extraction with Organic Solvent)

[0094]Nalmefene HCl aqueous mother liquor (145 kg); containing about 16 kg of “residue of evaporation”, with the following composition (% by HPLC area): nalmefene 90.97, naltrexone 0.23%, methyldiphenylphosphine oxide 1.1%, triphenylphosphineoxide 4.9%; was extracted with dichloromethane (2*30 L). The aqueous layer was then concentrated under vacuum distilling 128 kg of solvent. The suspension was diluted with water (7 kg). Sodium bisulfite 0.15 kg was added and the mixture maintained at 60-65° C. for four hours. The suspension was cooled to 0-5° C. and stirred for four hours. The solid was filtered and washed with dichloromethane (15 L) and acetone (15 L) obtaining 12.8 kg of nalmefene HCl. HPLC analysis (% by area): nalmefene 99.12%, naltrexone 0.05%. Methyldiphenylphosphine oxide and tri-phenylphosphineoxide below detection limit.

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

PropertyMeasurementUnit
temperatureaaaaaaaaaa
temperatureaaaaaaaaaa
temperatureaaaaaaaaaa
Login to View More

Abstract

The present invention relates to an improved process for recovery of nalmefene hydrochloride [17-(cyclopropylmethyl)-4,5- alpha-epoxy-6-methylenemorphinan-3,14-diol hydrochloride] from an aqueous composition containing nalmefene and certain impurities.

Description

FIELD OF THE INVENTION [0001]The present invention relates to an improved process for recovery of nalmefene hydrochloride [17-(cyclopropylmethyl)-4,5-alpha-epoxy-6-methylenemorphinan-3,14-diol hydrochloride] from an aqueous composition containing nalmefene and certain impurities.BACKGROUND OF THE INVENTION[0002]Nalmefene is a known opioid system modulator, with a distinct μ, δ, and κ receptor profile, which can inhibit pharmacological effects of both administered opioid agonists and endogenous agonists derived from the opioid system. The clinical usefulness of nalmefene comes from its ability to promptly (and selectively) reverse the effects of these opioid agonists.[0003]Nalmefene has been developed as the hydrochloride salt for use in the management of alcohol dependency, where it has shown good effect at doses of 10 to 40 mg taken when the patient experiences a craving for alcohol (Karhuvaara et al., Alcohol. Olin. Exp. Res., (2007), Vol. 31 (7): 1179-1187; Trial watch; Nalmefene...

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(United States)
IPC IPC(8): C07D489/08
CPCA61K31/485C07D489/08A61P25/00A61P25/30
Inventor DE FAVERI, CARLASTIVANELLO, MARIANO
Owner H LUNDBECK AS
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