Oxidative stress drug system with charge reversal capability and preparation method of oxidative stress drug system

A technology of oxidative stress and charge reversal, applied in the direction of medical preparations with non-active ingredients, medical preparations containing active ingredients, drug combinations, etc. Cell level, affecting life activities and other issues, to achieve the effect of improving utilization rate and therapeutic effect, enhancing oxidative stress, and enhancing encapsulation effect

Active Publication Date: 2019-12-17
HUBEI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it is difficult for this iron-mediated substance to be transported to the tumor site, and a good drug carrier is needed to achieve in vivo transportation; and even if it is transported to the tumor tissue through blood circulation, some drug carriers are difficult to be absorbed by tumor cells and enter the tumor Drug release internally; glutathione (GSH) plays an important role in cell protection against a variety of harmful substances, increasing the level of GSH in cancer cells has also been shown to increase resistance Applied chemical, radio and photodynamic therapy, as a well-known An intracellular antioxidant, glutathione exhibits a powerful scavenging effect on the highly reactive OH produced by the chemokinetic agent, thereby greatly increasing the resistance of cancer cells to the inhibition of oxidative stress; there are also many drug carriers , after producing the corresponding effect, it will continue to accumulate in the body, it is difficult to be cleared by the human body, and it will affect normal life activities

Method used

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  • Oxidative stress drug system with charge reversal capability and preparation method of oxidative stress drug system
  • Oxidative stress drug system with charge reversal capability and preparation method of oxidative stress drug system
  • Oxidative stress drug system with charge reversal capability and preparation method of oxidative stress drug system

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preparation example Construction

[0037] The preparation method of the oxidative stress drug system drug carrier system with charge reversal ability of the present invention mainly includes the following steps:

[0038] Step 1, Synthesis of Hollow Manganese Dioxide HMDN

[0039] (1) Quickly add 2.0~4.0mL TEOS (tetraethyl orthosilicate) to a mixed solution containing 30~60mL ethanol, 30~60mL deionized water and 1~6mL ammonia water (25%-28%), at room temperature Stir for 0.2 to 1 hour to form white colloidal suspended solid SiO 2 , and the SiO was cleaned by centrifugation with deionized water and ethanol 2 (alcohol twice / water twice, lyophilization without organic solvents) lyophilization to obtain sSiO 2 ;

[0040] (2) 180~300mg sSiO2 2 Fully disperse in deionized water, add this suspension to the mixed solution containing 500-800mg CTAB (remove 38-62mL deionized water, 38-62mL ethanol and 1-6mL ammonia water); stir the obtained mixed solution at room temperature for 0.2-1h , 400-700 mg KMnO4 was added qu...

Embodiment 1

[0051] A preparation method of an oxidative stress drug system with charge reversal ability, specifically comprising the following steps:

[0052] 1. Preparation of hollow manganese dioxide HMDN

[0053] (1) Quickly add 3.0mL TEOS to a mixed solution containing 37mL ethanol, 5mL deionized water, and 1.6mL ammonia water (ammonia water concentration 25%-28%), stir at room temperature for 0.5h, and form a white colloidal suspended solid SiO 2 , and the SiO was cleaned by centrifugation with deionized water and ethanol 2 (alcohol twice / water twice, freeze-drying without organic solvents), freeze-drying to obtain sSiO 2 ;

[0054] (2) 200mg sSiO2 was fully dispersed in 40mL deionized water, and then the suspension was added to the mixed solution containing 600mg CTAB (the mixed solution was composed of 60mL deionized water, 60mL ethanol and 4.5mL ammonia water, then stirred at room temperature for 0.5 h, quickly add 600mg KMnO 4 Then continue to react for 6h, collect by centri...

Embodiment 2

[0073] The preparation method of an oxidative stress drug system with charge reversal ability specifically includes the following steps: Weigh 200 mg of HMDN and dissolve it in 100 mL of tris (pH 8.0), add 200 mg of GA-Fe, and store under nitrogen protection at 25 to 35 ° C. Stir lightly for 24 hours, then add 100ml of tris solution (30mg / ml, pH 7.4) dropwise with PEI and react for 2 hours, finally add 200mg PASP-API and react for 24 hours, then wash with tris and deionized water and lyophilize.

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Abstract

The invention discloses a drug carrier system, which is obtained by the following steps: taking hollow manganese dioxide (HMDN) as a matrix, loading a coordination polymer (GA-Fe) of gallic acid and iron, encapsulating by branched polyethyleneimine (PEI), and encapsulating by polyaspartic acid (PASP-API) grafted with imidazole. According to the drug carrier system provided by the invention, through ionization of imidazolyl, charge reversal of the drug carrier can be realized to overcome an EPR effect to reach a tumor site. Meanwhile, the drug carrier system is decomposed in a tumor cell subacid environment, GA-Fe is released to serve as a catalyst of a Fenton reaction, hydrogen peroxide in tumor cells can continuously generate hydroxyl radicals (.OH), and the tumor cells are killed; and HMDN can react with glutathione (GSH) in tumor cells, .OH consumed by GSH is effectively inhibited, oxidative stress in the cells is enhanced, and the treatment effect is greatly improved.

Description

technical field [0001] The invention belongs to the field of drug carriers, and in particular relates to an oxidative stress drug system with charge reversal capability and a preparation method thereof. Background technique [0002] In recent years, with the deterioration of the natural environment, the incidence of cancer is increasing. Traditional cancer treatments include: surgery, chemotherapy and radiotherapy. Chemotherapy is the main anti-tumor treatment, but it is challenged by multidrug resistance (MDR), which largely limits the efficacy of chemotherapy. And often use high doses and increase the frequency of dosing. However, high doses and increased dosing frequency will not significantly improve the therapeutic effect, but will often bring serious adverse side effects to normal tissue cells, which may further worsen drug resistance. [0003] Research progress in ROS-based nanotherapeutics in recent years studies the underlying material chemistry of nanomaterials ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/59A61K47/52A61K33/26A61K31/192A61P35/00
CPCA61K47/59A61K47/52A61K33/26A61K31/192A61P35/00A61K2300/00
Inventor 李草段军林徐翔宇陈重银万立辉江兵兵
Owner HUBEI UNIV
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