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

Water-soluble andrographolide derivatives, preparation method thereof and application on medicine

A technology of andrographolide, derivatives, applied in antipyretics, antibacterial drugs, drug combinations and other directions, can solve the problems of complex components, difficult quality control, toxic and side effects, etc.

Inactive Publication Date: 2013-12-04
UNITRIS BIOPHARMA
View PDF10 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in the preparation process of these products, the structural skeleton of the active ingredient andrographolide has been changed to varying degrees, and clinically exhibited different degrees of toxic and side effects. In addition, the main component of Xiyanping injection is 20 A mixture of various sulfonated products, and the structure of many sulfonated products is unknown, the composition is complex, and the quality control in the production process is quite difficult

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
  • Water-soluble andrographolide derivatives, preparation method thereof and application on medicine
  • Water-soluble andrographolide derivatives, preparation method thereof and application on medicine
  • Water-soluble andrographolide derivatives, preparation method thereof and application on medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032]

[0033] step 1:

[0034] Add 1.93g of andrographolide (III), 15mL of acetone and 134mg of p-toluenesulfonic acid successively to a 50mL single-necked flask equipped with a spherical reflux condenser, react for 1 hour under stirring and reflux, cool to room temperature, and add 100mL of ethyl acetate to the system The ester was washed successively with saturated sodium bicarbonate solution and water, dried, concentrated under reduced pressure, and purified to obtain 1.99 g of white solid product II.

[0035] 1 H NMR (400MHz, CDCl 3 ): δ6.920(t, J=6.0Hz, 1H), 5.020(s, 1H), 4.892(s, 1H), 4.613(s, 1H), 4.654(s, 1H), 4.436(m, 1H) , 4.265(m, 1H), 3.950(d, J=11.7Hz, 1H), 3.477(m, 1H), 3.175(d, J=11.7Hz, 1H), 2.559(m, 2H), 2.400(m, 1H), 1.960(m, 2H), 1.750(m, 5H), 1.400(s, 3H), 1.360(s, 3H), 1.284(m, 3H), 1.195(s, 3H), 0.925(s, 3H) ); MS (ESI) m / z: 391[M+1].

[0036] Step 2:

[0037] Add 1.95g of compound II, 0.98g of sulfur trioxide triethylamine salt and 10mL of met...

Embodiment 2

[0040]

[0041] In the 50mL one-necked flask, add 1.53g compound Ia, 10g cationic resin (Amberlite IR120) and 20 mL of methanol, stirred at room temperature for 15 minutes, filtered, the solid was washed with methanol, the organic phases were combined, part of the methanol solution was taken, and concentrated under reduced pressure to obtain a white solid product Ib.

[0042] MS(ESI) m / z: 429[M-1].

[0043] The above methanol solution was washed with saturated NaHCO 3 The pH value of the solution was adjusted to pH=7, and concentrated under reduced pressure to obtain 1.15 g of white solid product Ic.

[0044] 1 H NMR (400MHz, D 2 O): δ6.988(t, J=6.4Hz, 1H), 5.608(s, 1H), 4.786(s, 1H), 4.540(d, J=3.6Hz, 2H), 4.503(s, 1H), 3.970(d, J=12.4Hz, 1H), 3.371(m, 2H), 2.560(m, 2H), 2.309(m, 1H), 1.934(m, 2H), 1.694(m, 4H), 1.222(m , 3H), 1.055(s, 3H), 0.591(s, 3H); MS(ESI) m / z: 429(M-1).

Embodiment 3

[0046]

[0047] Add 42.05g of andrographolide (III) and 150mL of pyridine sequentially into a 500mL three-necked flask equipped with a thermometer, cool to zero, add 30.95g of sulfur trioxide pyridinium salt, stir to fully dissolve, rise to room temperature, react for 3 hours, and pour into the system 500 mL of ethyl acetate was added to dilute and stirred for 5 minutes to obtain white solid products Id (24.31 g), Ie (2.73 g) and If (7.34 g) after purification.

[0048] Id: 1 H NMR (400MHz, CD 3 OD): δ8.910(d, J=5.6Hz), 8.703(m, 1H), 8.156(m, 2H), 6.857(t, J=6.4Hz, 1H), 5.040(d, J=5.2Hz, 1H), 4.879(s, 1H), 4.666(s, 1H), 4.483(dd, J 1 =10.0Hz,J 2 =6.4Hz, 1H), 4.183(m, 3H), 3.323(m, 1H), 2.621(m, 2H), 2.410(m, 1H), 1.743-1.990(m, 7H), 1.325(m, 2H) , 1.205(s, 3H), 0.787(s, 3H); MS(ESI) m / z: 429[M-1].

[0049] Ie: 1 H NMR (400MHz, CD 3 OD): δ8.909(d, J=5.6Hz, 2H), 8.705(m, 1H), 8.155(m, 2H), 6.847(t, J=6.4Hz, 1H), 5.020(d, J=5.7 Hz, 1H), 4.879(s, 1H), 4.660(s, 1H), 4.46...

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 water-soluble andrographolide derivatives, a preparation method thereof and application on medicine, and particularly, relates to water-soluble andrographolide derivatives shown in the general formula I and a mixer thereof, as well as the use of the water-soluble andrographolide derivatives and the mixer on antiphlogistic, antifebrile, antibacterial and other medicines, and the definitions of all substituent groups in the general formula are the same as those in the specification.

Description

technical field [0001] The invention relates to a water-soluble andrographolide derivative, a preparation method thereof and its application in medicine. Background technique [0002] Andrographis paniculata is an annual herbaceous plant of Acanthaceae. It has the functions of clearing heat, detoxifying, reducing inflammation, reducing swelling and relieving pain. It mainly grows in the warm zone south of the Yangtze River in my country, as well as in tropical or subtropical Fujian, Guangdong, Guangxi, Hunan and other places. Studies have shown that the medicinal active ingredient of Andrographis paniculata is andrographolide, and its structural formula is as follows: [0003] [0004] Andrographolide is a diterpenoid lactone compound, slightly soluble in methanol or ethanol, almost insoluble in water. Because andrographolide is insoluble in water, it can only be administered orally and has low bioavailability. In order to solve the water solubility problem of andrograp...

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): C07D307/60A61K31/341A61P29/00A61P31/04A61P31/12
Inventor 张富尧陈谦益
Owner UNITRIS BIOPHARMA
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