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Multi-targeting antitumor composite preparation and preparation method thereof

A compound preparation, anti-tumor technology, applied in the field of biomedical materials, can solve the problem of high cost of tumor vaccine development, such as tumor cells, and achieve the effect of overcoming high development cost, efficient treatment, and preventing excessive development

Active Publication Date: 2015-11-11
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the early stage of immunotherapy, the Fu vesicle drug delivery system is used to inhibit the development of tumors, prevent excessive tumor development, improve the therapeutic effect, and overcome the defects of high development costs of existing tumor vaccines and the immune escape characteristics of tumor cells.

Method used

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  • Multi-targeting antitumor composite preparation and preparation method thereof
  • Multi-targeting antitumor composite preparation and preparation method thereof
  • Multi-targeting antitumor composite preparation and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0059] Mix Pluronic F127, acetic anhydride and dimethyl sulfoxide, and react at room temperature for 30 hours to obtain a reaction mixture; then drop the reaction mixture into anhydrous ether, and a precipitate precipitates out; then add dichloromethane, shake well to make DMSO and ether A homogeneous solution is formed, which is conducive to the full precipitation of the Pluronic F127-aldehyde product, and then the poor solvent ether is added to form a precipitate and separate the product from other substances; it is allowed to stand at 4°C for 15 hours; then the mixture is filtered with suction, and the filter cake is vacuum-dried to obtain Pluronic Rangnic F127-aldehyde; add Pluronic F127-aldehyde, cholesterol, and concentrated hydrochloric acid into absolute ethanol, and reflux for 2.5 hours; then the reaction solution is filtered by suction and washed with water until neutral to obtain a waxy solid; then the waxy solid Soak in NaOH solution with a concentration of 0.1M and...

Embodiment 2

[0074] Weigh 335mg of BSA (bovine serum albumin) into a 25ml round bottom flask, add 10ml of 0.1mol / LPBS solution, fully dissolve, stir at 10r / min, and take another 25.0mg of DOX·HCl (doxorubicin hydrochloride) to dissolve in 1.5 In mlDMF, after BSA and DOX were fully mixed, 3.68ml of glutaraldehyde diluted 20 times was added dropwise at a rate of 4 drops / min, reacted in the dark at room temperature for 6h, centrifuged at 4°C and 3000rpm for 10min to take the supernatant, Dialyze with 0.01mol / LPBS solution at 4°C for 4 days, and change the dialysate from time to time according to the color of the dialyzed fluid. After the dialysis was completed, the dialysate was taken out, freeze-dried, made into DOX-BSA, and stored at -40°C for future use. The concentration of PBS determines the ionic strength of the solution, which will affect the properties of BSA and the product DOX-BSA; increasing the feeding of DOX·HCl can reduce the production of BSA-BSA, which is beneficial to the cro...

Embodiment 3

[0085] Activation of folic acid: Weigh 50.87mg FA (folic acid) into a 10ml round bottom flask, add 1.0ml DMF solution, fully dissolve, stir at 120r / min, take another 69.0mg N -Hydroxysuccinimide (NHS) and 116.5mg dicyclohexylcarbodiimide (DCC) were dissolved in 0.7 and 1.0mlDMF respectively, reacted overnight under dark conditions, collected the supernatant after centrifuging at 8000r / m for 10min (a , folic acid activator); FA-DOX synthesis: another 50.0mgDOX . HCl was dissolved in 1.3ml DMF, and the dissolved DOX solution was added dropwise to the supernatant of the folic acid activator, and reacted at room temperature, 120r / min, and protected from light for 6h. Centrifuge at 8000r / m for 10min, take the supernatant (b), and use pure water, anhydrous methanol, anhydrous ethanol, ether, acetonitrile and a mixed solvent of two or more of them to precipitate the FA-DOX product in the solution, It was found that its precipitation was most thorough in 30% anhydrous methanol / 70% et...

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Abstract

The invention discloses a multi-targeting antitumor composite preparation and a preparation method thereof. The multi-targeting antitumor composite preparation comprises a Fu vesicle suspension, DOX-BSA and FA-DOX. A vesicle administration system is prepared through integrating immunotherapy, positive targeting chemotherapy medicine drug molecules and a passive targeting administration system realize in order to realize low toxicity and high efficiency treatment of tumors, and the vesicle administration system can obviously slowly release Fu to effectively containment tumor development and has small influences on tumor bearing bodies; a newly synthesized immunogen can obtain an antibody with high sensitivity, so foundation is laid for formation of an immune compound macromolecule required by immunotherapy; and the micro-molecular compound FA-DOX has a molecule bridging effect in immunotherapy to promote formation of the immune compound macromolecule. The composite preparation has obviously better curative effects than simple particle administration chemical treatment or simple immunotherapy, has obviously low toxicity, can improve the antitumor effect, and is an anticancer composite preparation with wide research and application prospect.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and in particular relates to a multi-target anti-tumor compound preparation and a preparation method thereof. The compound preparation can activate autoimmunity and improve the anti-tumor effect. Background technique [0002] Currently, tumor treatment methods mainly include surgery, radiotherapy, chemotherapy, and biological therapy, each of which has its own status and role in tumor treatment because of its advantages and disadvantages. Chemotherapy uses the cytotoxicity of chemical drugs to kill tumor cells, thereby inhibiting the growth of tumors. However, small molecule chemotherapeutic drugs often lack specific groups that can identify tumor cells, resulting in a large amount of distribution in non-tumor tissues. Increasing the dosage often brings more intense toxic side effects to the body when increasing the curative effect. Clinically, suboptimal doses are usually given to reduce sev...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K39/00A61K47/34A61K47/26A61K47/28A61K47/48A61K31/513A61K31/704A61P35/00
Inventor 杨红龚珠萍邓安平刘迪吕小燕王雪姚枫枫付佩赵成龙
Owner SUZHOU UNIV
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