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Preparation method of podophyllotoxin twin drug nanoparticles

A podophyllotoxin and nanoparticle technology, applied in nanotechnology, nanotechnology, nanomedicine, etc., can solve the problems of low water solubility and poor efficacy of anticancer drugs

Active Publication Date: 2022-02-11
CHENGDU UNIVERSITY OF TECHNOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The invention relates to the field of anticancer drugs and aims to solve the technical problems of poor curative effect and low water solubility of anticancer drugs

Method used

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  • Preparation method of podophyllotoxin twin drug nanoparticles
  • Preparation method of podophyllotoxin twin drug nanoparticles
  • Preparation method of podophyllotoxin twin drug nanoparticles

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0059] An invention of podophyllotoxin twin-drug nanoparticles, comprising the steps of:

[0060] (1) Weigh podophyllotoxin (41.6mg, 0.1mmol), 3,3'-dithiodipropionic acid (21.2mg, 0.1mmol), tetramethylaminopyridine (37.5mg, 0.3mmol), 1-ethyl Dimethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (19.3mg, 0.1mmol) was dissolved in 15ml of dichloromethane at room temperature, stirred at room temperature for 6h, monitored by TLC during the stirring process, and the spot plate was visible A product is produced. Podophyllotoxin twin drug C1 was collected by column chromatography.

[0061] C1 NMR data are as follows: MS(ES), m / z: 1025.23[M+Na] +

[0062] 1 HNMR (400MHz, CDCl 3 , ppm): δ=6.79(s, 2'-H), δ=6.53(s, 5'-H), δ=6.36~6.38(d, 2,6-H), δ=5.98~5.97(d , 10′-H), δ=5.94~5.92(d, 7′-H), δ=4.61~4.60(d, 7-H), δ=4.41~4.37(q, 9-H), δ=4.20 ~4.16(t, 9-H), δ=3.81~3.71(t, 10,11,12-H), δ=3.04~2.96(m, 13,15-H), δ=2.95~2.94(d, 8-H), δ=2.94~2.90(t, 8″-H), δ=2.90~2.84(m, 13, 16-H), δ...

example 2

[0067] (1) Weigh podophyllotoxin (41.6mg, 0.1mmol), adipic acid (15.3mg, 0.1mmol), tetramethylaminopyridine (25mg, 0.2mmol), 1-ethyl-(3-dimethylamino Propyl)carbodiimide hydrochloride (19.3mmg, 0.1mmol) was dissolved in 10ml of dichloromethane at room temperature, stirred at room temperature for 6h, monitored by TLC during the stirring process, and the product was formed by spotting. Column chromatography, collection and rotary evaporation to obtain podophyllotoxin gemstone C2a.

[0068] C2a twin drug NMR data are as follows: MS (ES), m / z: 961.3 [M+Na] +

[0069] 1 HNMR (400MHz, CDCl 3, ppm): δ=6.75(s, 2′-H), δ=6.55(s, 5′-H), δ=6.39(s, 2, 6-H), δ=5.97(s, 10′- H), δ=5.89~5.87(d, 7'-H), δ=4.61~4.60(d, 7-H), δ=4.37~4.32(t, 9-H), δ=4.17~4.11 (m, 9-H), δ = 3.80 ~ 3.76 (d, 10, 11, 12-H), δ = 2.97 ~ 2.92 (d, 8-H), δ = 2.88 ~ 2.78 (m, 8'-H ), δ=2.49~2.48(s, 14,15-H), δ=1.78~1.75(m, 13,16-H)

[0070]

[0071] (2) Weigh 2mg of podophyllotoxin and dissolve it in 2ml of N, N-dim...

example 3

[0073] (1) Weigh podophyllotoxin (41.6mg, 0.1mmol), pimelic acid (16.0mg, 0.1mmol), tetramethylaminopyridine (25.0mg, 0.2mmol), 1-ethyl-(3-dimethyl Aminopropyl) carbodiimide hydrochloride (19.2 mg, 0.1 mmol) was dissolved in 10 ml of dichloromethane at room temperature, stirred at room temperature for 6 h, and monitored by TLC during the stirring process. Column chromatography, collection and rotary evaporation were obtained podophyllotoxin gemin C2b.

[0074] C2b twin drug NMR data are as follows: MS (ES), m / z: 975.3 [M + Na] +

[0075] 1 HNMR (400MHz, CDCl 3 , ppm): δ=6.74(s, 2'-H), δ=6.54(s, 5'-H), δ=6.38(s, 2, 6-H), δ=5.99~5.95(d, 10 '-H ), δ=5.90~5.86(d, 7'-H), δ=4.61~4.60(s, 7-H), δ=4.38~4.34(t, 9-H), δ=4.21~4.19 (d, 9-H), δ = 3.80 ~ 3.75 (d, 10, 11, 12-H), δ = 2.96 ~ 2.90 (q, 8-H), δ = 2.87 ~ 2.75 (m, 8'-H ), δ=2.52~2.38(m, 14,15,16-H), δ=1.79~1.66(m, 13,15,17-H)

[0076]

[0077] (2) Weigh 2mg of podophyllotoxin and dissolve it in 2ml of N,N--dimethylformami...

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Abstract

A preparation method of podophyllotoxin twin drug nanoparticles is characterized in that podophyllotoxin is mainly used as a raw material for twin drugs, -OH on podophyllotoxin and -COOH on a connexon are subjected to esterification coupling or -OH on podophyllotoxin and nitrobenzene on the connexon are substituted, and two podophyllotoxin molecules are connected to form the podophyllotoxin twin drug. The podophyllotoxin twin drug is dissolved in an organic solvent, a formed solution is dropwise added into an aqueous solution under the condition of constant-speed stirring, and the podophyllotoxin twin drug nanoparticles is prepared by adopting a nano precipitation method. The reaction conditions are mild, and the prepared podophyllotoxin twin-drug nanoparticles can improve the solubility of podophyllotoxin in an aqueous solution, increase the uptake of podophyllotoxin by tumor cells, improve the cytotoxicity and enhance the anti-tumor effect. The nanoparticles prepared by the invention are used in the field of cancer treatment.

Description

technical field [0001] The invention belongs to the field of anticancer medicine and chemical industry, and relates to the invention of a podophyllotoxin twin-drug nanoparticle. Background technique [0002] Podophyllotoxin (Podophyllotoxin) is a lignan anti-tubulin agent anti-tumor component extracted from the roots and stems of the natural Berberaceae Podophyllum plant-Sinopodophyllum (also known as gallinaceous). It is white crystalline powder, odorless and hygroscopic. Sinopodophyllum is mainly distributed in Gansu Province and other places in my country. The podophyllotoxin extracted from Sinopodophyllum (also known as gallinacein) can be made into ointment and tincture for clinical application. After the successful use of podophyllotoxin in the treatment of venereal diseases in 1942, there was growing interest in the application of podophyllotoxin to the treatment of tumors. Podophyllotoxin can effectively inhibit the assembly of microtubules in tumor cells, so monom...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/55A61K47/69A61K31/365A61P35/00B82Y5/00B82Y30/00B82Y40/00C07D519/00
CPCA61K47/6929A61K47/55A61K31/365A61P35/00C07D519/00B82Y5/00B82Y30/00B82Y40/00
Inventor 邱能马颖榆
Owner CHENGDU UNIVERSITY OF TECHNOLOGY