Eutectic crystal of TAF (tenofovir alafenamide) and vanillic acid and preparation method of eutectic crystal

A technology for tenofovir alafenamide and vanillic acid, which is applied in the field of co-crystals of tenofovir alafenamide and vanillic acid and their preparation, can solve the problem of drug stability and insufficient hygroscopic thermal stability and other problems, to achieve the effect of reducing material storage and quality control costs, reducing the sensitivity of environmental humidity and temperature, and strong economic value

Active Publication Date: 2018-12-14
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] It has been found through experiments that although the stability of the hemifumarate of tenofovir alafenamide has been improved, it is in terms of hygroscopicity (wetting weight gain of about 0.65%) and thermal stability (melting point is about 131 ° C) There are still deficiencies that may cause drug stability problems during production and storage

Method used

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  • Eutectic crystal of TAF (tenofovir alafenamide) and vanillic acid and preparation method of eutectic crystal
  • Eutectic crystal of TAF (tenofovir alafenamide) and vanillic acid and preparation method of eutectic crystal
  • Eutectic crystal of TAF (tenofovir alafenamide) and vanillic acid and preparation method of eutectic crystal

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Weigh 2g of tenofovir alafenamide and 0.7056g of vanillic acid, add 4mL of butanone and water mixed solvent to obtain a suspension, stir the suspension at room temperature for 24h, filter, and dry the solid. Tenofovir alafenamide-vanillic acid co-crystal white powder.

Embodiment 2

[0060] Weigh 40 mg of tenofovir alafenamide and 14 mg of vanillic acid, add 0.5 mL of acetonitrile and water mixed solvent to obtain a suspension, stir the suspension at room temperature for 3 h, centrifuge at 6000 rpm for 5 min, discard the supernatant liquid, the lower layer of solid was removed and dried to obtain the white powder of tenofovir alafenamide-vanillic acid eutectic.

Embodiment 3

[0062] Weigh 80 mg of tenofovir alafenamide and 28 mg of vanillic acid, add 1 mL of butanone and water mixed solvent to obtain a suspension, stir the suspension at room temperature for 3 h, centrifuge at 6000 rpm for 5 min, discard the supernatant liquid, the lower layer of solid was removed and dried to obtain the white powder of tenofovir alafenamide-vanillic acid eutectic.

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Abstract

The invention discloses a eutectic crystal of TAF (tenofovir alafenamide) and vanillic acid and a preparation method of the eutectic crystal. The eutectic crystal has the structural formula shown in the specification. In the eutectic crystal, the mole ratio of TAF to vanillic acid is 1:1. Besides, the invention also discloses the preparation method of the eutectic crystal and an application of theeutectic crystal. The provided eutectic crystal of TAF and vanillic acid has higher melting point, improved heat stability and improved moisture absorption, the sensitivity to the environment humidity and temperature is reduced in the preparation and storage process, the production and aftertreatment process of drugs is simplified, the material storage and quality control cost is reduced, and theeutectic crystal of TAF and vanillic acid has higher economic value and is more suitable for being used as a crude drug. Besides, the eutectic crystal displays good crystallinity and is easy to prepare and applicable to industrial large-scale production.

Description

technical field [0001] The invention relates to a co-crystal of tenofovir alafenamide and vanillic acid and a preparation method thereof. Background technique [0002] Tenofovir alafenamide (tenofovir alafenamide, TAF) is an innovative, targeted tenofovir prodrug developed by Gliead Sciences, which was approved by the US FDA on November 10, 2016. For the treatment of chronic hepatitis B virus infection in adults with compensated liver disease (trade name ). with previous generation products (Tenofovir disoproxil fumurate, TDF), only need less than one-tenth of the dose to achieve similar antiviral efficacy, so it has better safety. The chemical name of tenofovir alafenamide is 9-[(R)-2-[[(S)-[[(S)-1-(isopropoxycarbonyl)ethyl]amino]phenoxyoxy Phosphino] methoxy] propyl] adenine, the chemical structure is as follows. [0003] [0004] It has been found through experiments that although the stability of the hemifumarate of tenofovir alafenamide has been improved, in t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F9/6561C07C65/21C07C51/43A61K31/675A61P31/20A61P31/18
CPCA61P31/18A61P31/20C07B2200/13C07C65/21C07F9/65616
Inventor 陈嘉媚罗苏兰钱宇胡文浩
Owner SUN YAT SEN UNIV
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