Rebamipide monohydrate crystal form and preparation method thereof

A technology of monohydrate and rebamipide, which is applied in the field of crystal form of rebamipide monohydrate and its preparation, can solve the problems affecting the stability, dissolution and bioavailability of preparations, affecting the quality and safety of pharmaceutical preparations issues of sexuality and effectiveness

Active Publication Date: 2015-03-18
CHONGQING HUIZHI PHARMA RES INST +1
View PDF5 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

An API may exist in different polymorphic forms, and different polymorphic forms of the API may have different chemical and physical properties, including melting point, chemical reactivity, solubility, density, etc. These characteristics directly affect the handling of APIs and preparations and production, and may also affect the stability, dissolution and bioavailability of the preparation, thereby affecting the quality, safety and effectiveness of the pharmaceutical preparation

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
  • Rebamipide monohydrate crystal form and preparation method thereof
  • Rebamipide monohydrate crystal form and preparation method thereof
  • Rebamipide monohydrate crystal form and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1 Preparation of rebamipide sodium salt or potassium salt

[0038] Add 600ml of methanol, 64g of rebamipide, 17g of sodium hydroxide or 18g of potassium hydroxide into a 1000ml three-necked flask, stir and heat up to 60-65°C, the solid is completely dissolved, filter while it is hot, and cool the filtrate to 0-5°C for analysis. crystallize for 3 hours, filter with suction, wash the filter cake with ice methanol, dry under reduced pressure at 60°C for 6-7 hours, get 64g of rebamipide sodium salt or 66g of rebamipide potassium salt.

Embodiment 2

[0039] Example 2 Preparation of rebamipide monohydrate crystal form

[0040] Add 30ml of methanol, 12ml of water, and 3g of rebamipide sodium salt prepared according to Example 1 into a 100ml three-necked flask, heat to 60-80°C to completely dissolve the solid, add 0.03g of activated carbon, and reflux for 1h for decolorization. Filtrate hot, cool the filtrate to room temperature 20-25°C, adjust to 2-5°C with concentrated hydrochloric acid, precipitate a solid, stir for 1 hour, filter with suction, wash the filter cake with 30ml of ice water, and dry it in vacuum at 40°C for 15 hours to obtain the Ruixin of the present invention. Bappet monohydrate crystal form.

[0041] X-ray powder diffraction pattern (XRPD) see attached figure 1 ; Infrared absorption spectrum (IR) see attached figure 2 ; Differential thermal and thermal gravimetric analysis test chart (DTA-TG) see attached image 3 ; Loss on drying: 4.96% (test method: 105°C, 3h, drying under normal pressure).

Embodiment 3

[0042] Example 3 Preparation of rebamipide monohydrate crystal form

[0043] Add 60ml of ethanol, 30ml of water, and 3g of rebamipide potassium salt prepared according to Example 1 into a 100ml three-necked flask, heat to 60-80°C to completely dissolve the solid, add 0.03g of activated carbon, and reflux for 1h for decolorization. Filtrate hot, cool the filtrate to room temperature 20-25°C, adjust to 2-5°C with concentrated hydrochloric acid, precipitate a solid, stir for 1 hour, filter with suction, wash the filter cake with 30ml of ice water, and dry it in vacuum at 40°C for 15 hours to obtain the Ruixin of the present invention. Bappet monohydrate crystal form.

[0044] The X-ray powder diffraction spectrum, infrared absorption spectrum, differential thermal and thermogravimetric analysis test spectrum are consistent with the crystal form obtained in Example 2.

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 rebamipide monohydrate crystal form and a preparation method thereof. The invention further relates to a pharmaceutical composition taking a rebamipide monohydrate containing the crystal form as an active compound and application of the pharmaceutical composition in manufacturing of medicaments for treating diseases related to gastric ulcer, acute gastritis, chronic gastritis and gastric mucosal injuries caused by acute exacerbation.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a crystal form of rebamipide monohydrate and a preparation method thereof, a drug combination containing the crystal form of rebamipide monohydrate as an active ingredient, and its Application in the manufacture of drugs for the treatment of gastric ulcer, acute gastritis, and gastric mucosal injury related diseases caused by acute exacerbation of chronic gastritis. Background technique [0002] Rebamipide, whose chemical name is 2-(4-chlorobenzamido)-3-[2(1H)-quinolone-4-yl]propionic acid), has the following chemical structure: [0003] [0004] Rebamipide was developed by Japan's Otsuka Pharmaceutical Co., Ltd. and was launched in Japan in 1990 as an oral protective anti-ulcer drug for the treatment of gastric ulcer, acute gastritis and gastric mucosal damage caused by acute exacerbation of chronic gastritis. [0005] Japanese Pharmacopoeia JP16 reco...

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): C07D215/227A61K31/4704A61P1/04
CPCC07D215/227
Inventor 曾秀秀贾春荣
Owner CHONGQING HUIZHI PHARMA RES INST
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