Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

I type crystal of L-alanine-(14-rubescensin A)-ester trifluoroacetate, and preparation method thereof

A technology of ester trifluoroacetate, oridonin, applied in the field of type I crystallization and preparation of L-alanine-(14-oridonin) ester trifluoroacetate, can solve the problem of Problems such as poor product stability, difficult intravenous administration, and poor fluidity have been achieved to achieve the effects of stable production process, repeatable and controllable production process, and good crystal form stability

Inactive Publication Date: 2015-12-09
JIANGSU HENGRUI MEDICINE CO LTD
View PDF0 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, the oral bioavailability of oridonin is less than 5%, and the effective blood concentration cannot be reached; at the same time, oridonin is almost insoluble in water, so it is difficult to administer intravenously
Generally speaking, amorphous drug products have no regular crystal structure and often have other defects, such as poor product stability, fine crystallization, difficult filtration, easy agglomeration, poor fluidity, etc.

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
  • I type crystal of L-alanine-(14-rubescensin A)-ester trifluoroacetate, and preparation method thereof
  • I type crystal of L-alanine-(14-rubescensin A)-ester trifluoroacetate, and preparation method thereof
  • I type crystal of L-alanine-(14-rubescensin A)-ester trifluoroacetate, and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Embodiment 1: Preparation of L-alanine-(14-oridonin A) ester trifluoroacetate

[0040] Step 1: Preparation of N-Boc-L-alanine-(14-oridonin A) ester

[0041] Suspend 150g (0.41mol) oridonin (II), 195g (1.04mol) Boc-L-Ala in 1.35kg dichloromethane, cool in an ice bath to 0-5°C, add 213g (1.04mol) DCC, After stirring for 0.5h, the ice bath was removed, stirred at room temperature for 5h, and TLC confirmed that the reaction of the raw materials was complete (dichloromethane:methanol=10:1, raw material R f = 0.4, product R f = 0.6). The reaction solution was cooled to 0° C. and stood for 2 h, filtered, and the filter cake was washed with dichloromethane (300 g×3). The organic layers were combined and concentrated to obtain a white solid. Flash silica gel column chromatography (dichloromethane:methanol=100:1~60:1; v / v), collect product components, concentrate to dryness under reduced pressure to obtain about 140~165g of white solid powder. Add 600g of isopropyl ether to t...

Embodiment 2

[0044] Embodiment 2: Determination of the crystal form of the sample of Example 1

[0045] The solid sample X-ray powder diffraction pattern that makes in embodiment 1 sees image 3 , showing the characteristic absorption peak of the amorphous form, the DSC spectrum is shown in 4, and no melting characteristic absorption peak is seen below 300 ° C, so it is determined that the product is an amorphous solid.

Embodiment 3

[0047] Weigh 500mg of L-alanine-(14-oridonin) ester trifluoroacetate amorphous solid in a 25ml round bottom flask, add 5ml of acetone, stir to dissolve, slowly add 10ml of isopropyl ether at room temperature, stir After crystallization for 2.5 hours, suction filtration, the filter cake was washed with a small amount of acetone / isopropyl ether (V / V=1 / 2) mixed solvent and dried to obtain 370 mg of white solid, yield 74.0%. The X-ray powder diffraction pattern of this crystalline sample is shown in figure 1 . The crystallization is at about 6.85 (12.89), 8.09 (10.92), 11.30 (7.82), 13.71 (6.45), 14.08 (6.29), 14.35 (6.17), 16.40 (5.40), 17.41 (5.09), 18.19 (4.87), 18.44 (4.81), 20.12(4.41), 21.17(4.19), 23.38(3.80), 23.88(3.72), 24.42(3.64), 24.84(3.58), 25.72(3.46), 26.46(3.37), 27.22(3.27), 28.40 There are characteristic peaks at (3.14), 29.38(3.04), 31.26(2.86) and 31.79(2.81). DSC spectrum see figure 2 , with a sharp melting endothermic peak at 232.59°C, this crystal for...

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 present invention relates to an I-type crystal of L-alanine-(14-oridonin) ester trifluoroacetate and a preparation method therefor.The preparation method comprises crystallizing a L-alanine-(14-oridonin) ester trifluoroacetate solid in any crystal form or amorphous form in a single organic solvent or a mixed organic solvent thereof to obtain the I-type crystal of the L-alanine-(14-oridonin) ester trifluoroacetate.The I-type crystal of the L-alanine-(14-oridonin) ester trifluoroacetate obtained in the present invention has a good crystal form stability and chemical stability, and uses a crystallization solvent which has a low toxicity and low residue, and can be better used in clinical treatments.

Description

technical field [0001] The invention relates to type I crystal of L-alanine-(14-oridonin A) ester trifluoroacetate and its preparation method and use. Background technique [0002] Formula (I) compound is L-alanine-(14-Oridonin A) ester trifluoroacetate, it is [0003] [0004] Taking oridonin as the mother nucleus, after transformation and modification, the obtained oridonin ester derivatives; Oridonin (Oridonin) is a kind of kaurene extracted from Oridonin Diterpenoid natural organic compounds, accounting for more than 90% of the active ingredients of Rubescens japonicus, are the main active ingredients of anti-tumor. [0005] However, the oral bioavailability of oridonin is less than 5%, and the effective blood concentration cannot be reached; at the same time, oridonin is almost insoluble in water, so it is difficult to administer intravenously. Therefore, modifying its structure, improving its water solubility and activity, and developing it into a new antitumor dr...

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
IPC IPC(8): C07D493/08A61K31/352A61P35/00A61P35/02
CPCA61K31/352C07D493/08
Inventor 孙飘扬武乖利邱振均陈永江沈灵佳
Owner JIANGSU HENGRUI MEDICINE CO LTD
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
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