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

All-trans retinoic acid-camptothecin anticancer drug conjugate as well as preparation method and application thereof

A technology of all-trans retinoic acid and anti-cancer drugs, which is applied in drug combinations, anti-tumor drugs, and pharmaceutical formulations. effect of nature

Active Publication Date: 2015-04-01
ZHEJIANG UNIV
View PDF2 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] There are no related reports on the combination of SN-38 and ATRA

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
  • All-trans retinoic acid-camptothecin anticancer drug conjugate as well as preparation method and application thereof
  • All-trans retinoic acid-camptothecin anticancer drug conjugate as well as preparation method and application thereof
  • All-trans retinoic acid-camptothecin anticancer drug conjugate as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Example 1 Preparation of ATRA-SN38 conjugate (C10 hydroxyl)

[0055] The preparation method of a kind of ATRA-SN-38 conjugate (C-10 hydroxyl) of this embodiment (synthetic route sees figure 1 ),include:

[0056] SN-38 (500mg, 1.27mmol), DMAP (171.4mg, 1.40mmol), ATRA (383.2mg, 1.27mmol), EDC·HCl (268mg, 1.40mmol) were dissolved in 15mL DMF, and DIEA (180.9mg, 1.40mmol) was added ), reacted overnight, after removing the reaction solvent, the solid was dissolved in dichloromethane, washed 7 times with water, washed 1 time with saturated aqueous sodium bicarbonate solution, 5% citric acid and saturated saline successively, dried over anhydrous sodium sulfate, filtered, After collecting the filtrate, the solvent was removed under reduced pressure; the solid was separated and purified by column chromatography (ethyl acetate: n-hexane = 1:1) to obtain the product ATRA-SN38 conjugate 1 (hereinafter referred to as conjugate 1).

[0057] NMR data of conjugate 1:

[0058] 1 H...

Embodiment 2

[0059] Example 2 The first preparation method of the conjugate 1 nanoparticle

[0060] The conjugate 1 (20 mg) of Example 1 was dissolved in 1 mL of Tween 80 solution, and then slowly injected into water (final concentration 2 mg / mL), and gently shaken and vibrated to form nanoparticles, which were designated as RSN38. The nanoparticle solution can be directly used for clinical oral administration or injection.

Embodiment 3

[0061] Example 3 The second preparation method of conjugate 1 nanoparticles

[0062] The conjugate 1 (20 mg) obtained in Example 1 was dissolved in 1 mL of dimethyl sulfoxide (DMSO), and then rapidly injected into water (final concentration 2 mg / mL). The solution was dialyzed to remove DMSO and form nanoparticles. The nanoparticle solution can be directly used for clinical oral administration or injection.

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
Volumeaaaaaaaaaa
Volumeaaaaaaaaaa
Login to View More

Abstract

The invention discloses an all-trans retinoic acid-camptothecin anticancer drug conjugate as well as a preparation method and application thereof. The structural formula of the all-trans retinoic acid-camptothecin anticancer drug conjugate is shown in a formula (I), (II), (III), (IV), (V) or (VI). The all-trans retinoic acid-camptothecin anticancer drug conjugate has good solubility in Tween, polyoxyethylene castor oil, a Poly(ethylene adipate)-polylactic acid copolymer and a Poly(ethylene adipate)-poly (lactic acid-glycollic acid) copolymer, can be self assembled into nanometer grains in water, can be directly injected or taken orally or processed into other dosage forms. According to the all-trans retinoic acid-camptothecin anticancer drug conjugate disclosed by the invention, as all-trans retinoic acid and SN-38 or camptothecin take synergistic effect, compared with a conjugate only containing one of irinotecan, SN-38 and all-trans retinoic acid, the all-trans retinoic acid-camptothecin anticancer drug conjugate has good tumor suppression effect.

Description

technical field [0001] The invention belongs to the field of pharmacy, and in particular relates to an all-trans retinoic acid-camptothecin anticancer drug conjugate and a preparation method and application thereof. Background technique [0002] All-trans retinoic acid (ATRA), also known as tretinoin, retinoic acid, etc., is a natural derivative of vitamin A, an intermediate metabolite of vitamin A in the body, and is indispensable for maintaining growth and development substance. ATRA can inhibit cell proliferation and has a strong induction [0003] The role of tumor cell differentiation (Tang, X.H.Gudas, L.J.Retinoids, retinoic acid receptors, and cancer.Annu.Rev.Pathol., 2011,6:345), is the current domestic clinical treatment of acute promyelocytic leukemia, myeloid hyperplasia, etc. It is the drug of choice for malignant blood diseases, and it has also attracted much attention in other clinical fields such as skin diseases and some solid tumors. The structural formul...

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): C07D491/22A61K31/4745A61P35/00
CPCY02P20/55C07D491/22
Inventor 王杭祥
Owner ZHEJIANG UNIV
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