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Ethylenediamine cationic albumin antitumor nanoparticle as well as preparation method and application thereof

A cationization and ethylenediamine cationization technology, which is applied in the field of medicine, can solve the problems of low encapsulation efficiency and low drug loading rate, and achieve the effects of improving solubility, high safety, and good tumor targeting

Inactive Publication Date: 2018-04-20
THE THIRD AFFILIATED HOSPITAL INST OF FIELD SURGERY OF PLA ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Soo-Jeong Lim et al. loaded ATRA into solid lipid nanoparticles (SLN) and found that SLN can increase the stability of ATRA, but the drug loading rate is low, only 2.4%.
Zhang Jingru et al. prepared ATRA liposomes by the reverse phase evaporation method. The stability of each formulation was good, but the encapsulation efficiency was lower than 70%.
At present, the research on new nano-preparations of ATRA is in the laboratory stage, and no new preparations with good encapsulation efficiency, high drug loading rate, particle size and stability meeting clinical requirements have been obtained.

Method used

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  • Ethylenediamine cationic albumin antitumor nanoparticle as well as preparation method and application thereof
  • Ethylenediamine cationic albumin antitumor nanoparticle as well as preparation method and application thereof
  • Ethylenediamine cationic albumin antitumor nanoparticle as well as preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0046] Preparation of ATRA-eBSA-NPs: Weigh 4.5mg of ATRA into a 1.5ml centrifuge tube, add 0.9ml of absolute ethanol, fully dissolve to obtain the drug-containing organic phase (5mg / ml); weigh 50mg of eBSA and purify it with 10ml Dissolved in water and placed in a glass vial as the water phase; inject the organic phase into the water phase, and immediately use a cell sonicator to sonicate in an ice bath, with an ultrasonic power of 50W, supersonic for 5s and stop for 5s, and sonicate for 20min Then the solution in the vial is transferred to a high-pressure homogenizer, and the high-pressure homogenization is performed under 18000psi pressure for 15 cycles; then the solution in the vial is transferred to a 100ml round-bottomed flask, and the organic solution is removed by rotary evaporation in a 35°C water bath, protected from light, and decompressed. solvent to obtain ATRA-eBSA-NPs solution. The appearance of the solution is light yellow, transparent and opalescent, and there ...

Embodiment 2

[0049] Preparation of ATRA-eBSA-NPs: Weigh 10mg of ATRA into a 5ml centrifuge tube, add 2ml of absolute ethanol, fully dissolve to obtain a drug-containing organic phase (5mg / ml); weigh 100mg of eBSA, dissolve it in 10ml of purified water and place Put it in a glass vial as the water phase; inject the organic phase into the water phase, and immediately use a cell sonicator to sonicate it in an ice bath with an ultrasonic power of 50W, supersonicate for 5s and stop for 5s, and sonicate for 20min in total; then Transfer the solution in the vial to a high-pressure homogenizer, and homogenize under high pressure for 15 cycles at a pressure of 18,000 psi; then transfer the solution in the vial to a 100ml round-bottomed flask, and remove the organic solvent by rotary evaporation in a 35°C water bath, protected from light, under reduced pressure, that is ATRA-eBSA-NPs solution was obtained. The appearance of the solution is light yellow, transparent and opalescent, and there is Tynda...

Embodiment 3

[0052] Preparation of ATRA-eBSA-NPs: Weigh 50mg of ATRA into a 10ml centrifuge tube, add 10ml of absolute ethanol, fully dissolve to obtain a drug-containing organic phase (5mg / ml); weigh 500mg of eBSA and dissolve it in 50ml of purified water Put it in a glass vial as the water phase; inject the organic phase into the water phase, and immediately use a cell sonicator to sonicate it in an ice bath with an ultrasonic power of 50W, supersonicate for 5s and stop for 5s, and sonicate for 20min in total; then Transfer the solution in the vial to a high-pressure homogenizer, and homogenize under high pressure for 15 cycles at a pressure of 18,000 psi; then transfer the solution in the vial to a 100ml round-bottomed flask, and remove the organic solvent by rotary evaporation in a 35°C water bath, protected from light, under reduced pressure, that is ATRA-eBSA-NPs solution was obtained. The appearance of the solution is light yellow, transparent and opalescent, and there is Tyndall ph...

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Abstract

The invention discloses an ethylenediamine cationic albumin antitumor nanoparticle as well as a preparation method and application of the ethylenediamine cationic albumin antitumor nanoparticle. The albumin nanometer preparation is prepared by optimally using all-trans-retinoic acid (ATRA) as an anti-tumor active substance, taking ethylenediamine cationic albumin as a drug carrier, adding a dispersant and a solvent and using an albumin-binding nanoparticle technology, and the average particle size of the albumin nanometer preparation is less than 220 nm. The preparation method of the ethylenediamine cationic albumin antitumor nanoparticle comprises the following steps: dissolving the dispersant in water to prepare a water phase, dissolving ATRA in the solvent to prepare an oil phase, mixing the water phase and the oil phase, carrying out high-speed shearing, homogenizing, then evaporating through the solvent, and performing freeze-drying to obtain the albumin nanometer preparation. Byadopting the ethylenediamine cationic albumin antitumor nanoparticle, the nanometer particle size of albumin is reduced to the nanometer level to solve the problem of solubility, therefore, the surface of human albumin has positive charges to increase the adsorption between the human albumin and tumor cells of which the surfaces have negative charges, strengthen targeting of the ethylenediamine cationic albumin antitumor nanoparticle, reduce adverse reactions, improve the curative effect and enhance the applicability of clinical use.

Description

technical field [0001] The invention belongs to the pharmaceutical preparation in the technical field of medicine, and relates to an ethylenediamine cationized albumin anti-tumor nanoparticle and its preparation method and application, especially ethylenediamine cationized albumin as a carrier of all-trans retinoic acid in the preparation Use in nanoinjections. Background technique [0002] All-trans-retinoic acid (ATRA), a derivative of vitamin A, is currently the drug of choice for the treatment of acute promyelocytic leukemia. It has good curative effect, high complete remission rate, and does not cause diffuse intravascular Blood coagulation and other advantages. Recent studies have found that ATRA can inhibit cancer stem cells (CSC). In addition, literature reports that ATRA can significantly reduce the number of tumor spheres of breast cancer stem cells and the expression of CSC surface marker CD44, and significantly inhibit the growth of breast cancer cells and brea...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/42A61K45/00A61K31/203A61K9/19A61P35/00
CPCA61K9/0019A61K9/19A61K9/5169A61K31/203A61K45/00
Inventor 石三军李园园陈剑鸿罗明和明月
Owner THE THIRD AFFILIATED HOSPITAL INST OF FIELD SURGERY OF PLA ARMY MEDICAL UNIV
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