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

Reduction-responsive type camptothecin dimer and reduction-sensitive drug delivery system based on the camptothecin dimer

A delivery system, the technology of dihydroxyethyl disulfide, which is applied in the fields of biomedicine and nanomedicine, can solve the problems of poor water solubility of camptothecin, toxic and side effects, and low drug loading capacity, and achieves excellent anti-tumor, simple preparation, Water solubility and stability enhancement effect

Inactive Publication Date: 2019-02-01
HENAN NORMAL UNIV
View PDF3 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The present invention takes the anti-tumor small molecule drug camptothecin as the research object, and designs and synthesizes a reduction-responsive maleimide sulfide bond-linked camptothecin dimer prodrug, which is loaded on mPEG-b-PCL Under the entrapment of micelles, camptothecin has poor water solubility, low drug loading, and has relatively large toxic and side effects on normal tissues or organs.

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
  • Reduction-responsive type camptothecin dimer and reduction-sensitive drug delivery system based on the camptothecin dimer
  • Reduction-responsive type camptothecin dimer and reduction-sensitive drug delivery system based on the camptothecin dimer
  • Reduction-responsive type camptothecin dimer and reduction-sensitive drug delivery system based on the camptothecin dimer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Dissolve 511 mg (1.95 mmol) of triphenylphosphine in 5 mL of anhydrous THF and stir. Add 0.38 mL (1.95 mmol) of diisopropyl azoxylene to the above solution dropwise, and stir at -78°C for 5 min. After dissolving 0.25 mL (1.56 mmol) of triethylene glycol monomethyl ether in 5 mL of anhydrous THF, it was added dropwise to the reaction solution of diisopropyl azoxylene, and stirred at -78°C for 5 min. Afterwards, 121 mg (1.37 mmol) of neopentyl alcohol was dissolved in 2 mL of anhydrous THF and added to triethylene glycol monomethyl ether, and stirred at -78°C for 5 min. Finally, 497 mg (1.95 mmol) of dibromomaleimide was added to the above reaction solution, stirred at -78°C for 10 min, then transferred to room temperature, and magnetically stirred at room temperature for 20 h. The crude product was purified by column chromatography (volume ratio EA:PA=1:10-1:4), and then separated by medium-pressure preparation to obtain 325 mg of the off-white target product, Intermedi...

Embodiment 2

[0031] Weigh 123.2mg (0.8mmol) of 2-hydroxyethyl disulfide, 323.6mg (3.2mmol) of triethylamine and 230mg (0.8mmol) of TCEP.HCl and dissolve in 50mL of anaerobic-treated methanol, and stir at room temperature for 20min. Weigh 319.1mg (0.8mmol) of the intermediate 1 prepared in the example and dissolve it in 25mL of anaerobic-treated methanol, then add it to the above reaction solution, and the color changes from colorless to turmeric. Stir magnetically overnight at room temperature. The crude product was purified by column chromatography (volume ratio methanol:dichloromethane=1:200-1:50) to obtain 243.3 mg of the target pure intermediate 2 in the form of dark yellow oil with a yield of 77%. 1 H NMR (600MHz, CDCl 3 )δ3.91–3.81(m,2H),3.72(d,2H),3.69–3.57(m,5H),3.54(s,1H),3.48–3.42(m,2H),3.38(s,2H) ,2.28–1.96(m,1H).

Embodiment 3

[0033] Weigh 835.4mg (2.4mmol) of CPT and dissolve it in 25mL of anhydrous dichloromethane, add 482.35mg (2.4mmol) of p-nitrophenyl chloroformate and 585.9mg (4.8mmol) of DMAP under stirring, under anaerobic conditions Stir for 4h. Then weigh 395.1mg (1.0mmol) Intermediate 2 prepared in Example 2 and dissolve it in 16mL (anhydrous THF / CH 2 Cl 2 ) solution. Magnetic stirring was carried out at room temperature for 36 h. The crude product was purified by column chromatography (volume ratio methanol:dichloromethane=1:250-1:100) to obtain 525.9 mg of the yellow-green target product camptothecin dimer 3 with a yield of 64%. 1 H NMR (600MHz, CDCl 3)δ 8.38(s,2H),8.20(d,2H),7.93(d,2H),7.82(t,2H),7.66(t,2H),7.29(s,2H),5.69(d,2H) ,5.36(d,2H),5.29(d,4H),4.17(m,4H),3.51(m,12H),3.38(m,6H),2.25(m,2H),2.12(m,2H), 0.98(t,6H). 13 CNMR (151MHz, CDCl 3 ( s), 128.58–128.04(m), 120.26(d, J=0.9Hz), 95.92(s), 78.01(s), 71.89(s), 70.53(s), 70.02(s), 67.63(d, J =11.6Hz), 67.12(s), 59.01(s), ...

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 discloses a reduction-responsive type camptothecin dimer and a reduction-sensitive drug delivery system based on the camptothecin dimer, and belongs to the technical field of biomedicines and nano-medicines. Technical scheme main points are as follows: dibromomaleimide sequentially reacts with triethylene glycol monomethyl ether, 2,2-dihydroxyethyl disulfide and camptothecinto obtain the reduction-responsive type camptothecin dimer. The camptothecin dimer has a shown structural formula. The present invention also discloses a preparation method of the camptothecin dimer and a reduction-sensitive drug delivery system based on the camptothecin dimer. Compared with a camptothecin delivery system, the drug delivery system has a drug loading amount increased from 1 wt% to9.6 wt%. Besides, the drug delivery system has reduction sensitivity, good biocompatibility, and tumor cell proliferation inhibition ability. The reduction-responsive type camptothecin dimer can be used to prepare an anticancer drug delivery system with controlled release and targeting.

Description

technical field [0001] The invention belongs to the technical field of biomedicine and nanomedicine, and specifically relates to a reduction-responsive camptothecin dimer and a reduction-sensitive drug delivery system based on the camptothecin dimer. Background technique [0002] Camptothecin (CPT) is a DNA topoisomerase (TOPO I) inhibitor, which prevents DNA replication and RNA synthesis, and eventually leads to cell death. As a broad-spectrum anticancer drug, it can effectively inhibit Melanoma, breast cancer, prostate cancer, liver cancer, and colon cancer. However, the clinical application of camptothecin is limited due to the disadvantages of low water solubility, high toxicity, unstable lactone ring, and rapid clearance. In order to overcome these problems, a variety of camptothecin drug-loaded micelles have been developed to solve these problems, but due to factors such as low drug loading, poor stability, and uncontrollable drug release, it is difficult to realize t...

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): C07D519/00A61K47/54A61K47/34A61K31/4745A61P35/00
CPCA61K31/4745A61K47/34A61K47/545A61P35/00C07D519/00
Inventor 蒋涛王志莹王洁池彦伟董文佩张月辛鹏洋陈长坡
Owner HENAN NORMAL UNIV
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