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Multi-target anti-tumor compound 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 the high development cost, improving the therapeutic effect, and preventing excessive development.

Active Publication Date: 2018-01-12
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-target anti-tumor compound preparation and preparation method thereof
  • Multi-target anti-tumor compound preparation and preparation method thereof
  • Multi-target anti-tumor compound preparation and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Mix Pluronic F127, acetic anhydride and dimethyl sulfoxide, and react at room temperature for 30 h to obtain a reaction mixture; then drop the reaction mixture into anhydrous ether, and a precipitate precipitates out; then add dichloromethane, shake fully to make DMSO and Diethyl ether forms a homogeneous solution, which is conducive to the full precipitation of the Pluronic F127-aldehyde product, and then adds poor solvent diethyl ether to form a precipitate and separate the product from other substances; stand at 4°C for 15 hours; then filter the mixture with suction, and dry the filter cake in vacuum to obtain Pluronic F127-aldehyde; add Pluronic F127-aldehyde, cholesterol, and concentrated hydrochloric acid to 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 The solid was soaked in NaOH solution with a concentration of 0.1M and then suction-filtered....

Embodiment 2

[0076] Weigh 335 mg BSA (bovine serum albumin) into a 25 ml round bottom flask, add 10 ml 0.1 mol / L PBS solution, fully dissolve, stir at 10 r / min, and take another 25.0 mg DOX·HCl (doxorubicin Hydrochloride) was dissolved in 1.5ml DMF. After BSA and DOX were fully mixed, 3.68 ml of 20-fold diluted glutaraldehyde was added dropwise at a rate of 4 drops / min. Centrifuge at 3000 rpm for 10 min to take the supernatant, dialyze with 0.01 mol / L PBS 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 cross-linking of DOX·HCl and BSA; The degree of dilution,...

Embodiment 3

[0087] Activation of folic acid: Weigh 50.87 mg FA (folic acid) into a 10 ml round bottom flask, add 1.0 ml DMF solution, fully dissolve, stir at 120 r / min, and take another 69.0 mg N -Hydroxysuccinimide (NHS) and 116.5 mg dicyclohexylcarbodiimide (DCC) were dissolved in 0.7 and 1.0 ml DMF respectively, reacted overnight in the dark, centrifuged at 8000 r / m for 10 min, and the supernatant was collected solution (a, folic acid activator); synthesis of FA-DOX: another 50.0 mg DOX . HCl was dissolved in 1.3 ml DMF, and the dissolved DOX solution was added dropwise to the folic acid activator supernatant, and reacted at room temperature, 120 r / min, and protected from light for 6 h. Centrifuge at 8000 r / m for 10 min, 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 FA-DOX in the solution The product was found to be most thoroughly precipitated in 30% anhydrous methanol...

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Abstract

The invention discloses a multi-target anti-tumor compound preparation and a preparation method thereof. The multi-target anti-tumor compound preparation consists of Fu vesicle suspension, DOX-BSA and FA-DOX. In order to treat tumors with low toxicity and high efficiency, the vesicle drug delivery system prepared by comprehensive immunotherapy, active targeted chemotherapy drug molecules, passive targeted drug delivery system and other treatment methods can obviously slow release Fu and effectively curb the development of tumors. However, it has little effect on the tumor-bearing body; the newly synthesized immunogen can obtain antibodies with high sensitivity, which lays the foundation for the formation of immune complex macromolecules required for immunotherapy; the small molecule compound FA‑DOX can play a role in immunotherapy The bridging effect promotes the formation of immune complex macromolecules; the curative effect of the compound preparation of the present invention is obviously better than that of simple microparticle administration chemotherapy or simple immunotherapy, and it obviously has the characteristics of low toxicity and can improve the anti-tumor effect. Research and application prospects of anticancer compound preparations.

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 Patents(China)
IPC IPC(8): A61K9/51A61K39/00A61K47/26A61K47/28A61K47/60A61K31/513A61K31/704A61P35/00
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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