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Preparation method and application of oxygen-carrying hybrid protein loaded metal complex nano-system

A hybrid protein and metal-loaded technology, which is applied in the field of nanomedicine, can solve the problems of oxygen poisoning of the nervous system in the increase of lung burden, low improvement effect of oxygen at tumor sites, and poor stability of the oxygen carrier system, so as to improve the therapeutic effect, Improve drug efficacy and stabilize particle size

Pending Publication Date: 2021-03-26
GUANGDONG MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, it is difficult for oxygen-transfused red blood cells to penetrate blood vessels and enter the tumor, resulting in low oxygen improvement effect at the tumor site. At the same time, excessively high concentration of oxygen will also increase the burden on the lungs and oxygen toxicity in the central nervous system.
In addition, the introduction of artificial oxygen carriers to increase the oxygen content of tumor sites has been used, including perfluorocarbons, polyhemoglobin, cross-linked hemoglobin, hemoglobin liposomes, etc., but perfluorocarbons have certain toxicity, and simple hemoglobin and hemoglobin lipids The stability of the plastid oxygen-carrying system is not good. In addition, the preparation process of the current oxygen-carrying system is complicated, and it can only carry oxygen or small molecules of organic drugs at the same time. to be developed

Method used

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  • Preparation method and application of oxygen-carrying hybrid protein loaded metal complex nano-system
  • Preparation method and application of oxygen-carrying hybrid protein loaded metal complex nano-system
  • Preparation method and application of oxygen-carrying hybrid protein loaded metal complex nano-system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Preparation of hybrid protein-loaded complex drug nanosystem: mix albumin (20 mg) with reduced glutathione (10 mg), add 4 mL of double distilled water, shake on a shaker for 0.5 h, and adjust the pH to 8. Finally, use a 100kD ultrafiltration tube to ultrafilter excess reduced glutathione at a centrifugation rate of 3500 rpm.

[0032] After collecting the filtrate, add hemoglobin aqueous solution (1 mg / mL) under stirring, slowly add 0.5 mL of methanol dropwise under stirring, continue stirring for 0.5 h, then add 200 microliters of manganese tetrasulfonic acid phthalocyanine complex Chloroform solution (1 mg complex), after intermittent ultrasonic crushing in ice bath for 5 minutes, adjust the pH value to weak alkaline with saturated sodium carbonate solution and fully shake until clear, then use 100kD ultrafiltration tube to repeatedly ultrafilter, filter Organic solvents and unreacted small molecules are removed to obtain nanoparticles of hybrid protein-loaded complexe...

Embodiment 2

[0034] Preparation of hybrid protein-loaded complex drug nanosystem: mix albumin (20 mg) with reduced glutathione (10 mg), add 4 mL of double distilled water, shake on a shaker for 1 h, and adjust the pH to 8 with sodium carbonate at the same time , and finally use a 100kD ultrafiltration tube to ultrafilter excess reduced glutathione at a centrifugation rate of 3500 rpm.

[0035] After the filtrate was collected, hemoglobin aqueous solution (2 mg / mL) was added under stirring, and 1 mL of methanol was slowly added dropwise under stirring. After stirring for 0.5 h, 200 microliters of manganese tetrasulfonic acid phthalocyanine complex was added. Chloroform solution (1 mg complex), after intermittent ultrasonic crushing in an ice bath for 5 minutes, adjust the pH value to weak alkaline with saturated sodium carbonate solution and fully shake until clear, then use a 100kD ultrafiltration tube to repeatedly ultrafilter, filter out Organic solvents and unreacted small molecules are...

Embodiment example 3

[0037] Preparation of hybrid protein-loaded complex drug nanosystem: mix albumin (40 mg) with reduced glutathione (10 mg), add 4 mL of double distilled water, shake on a shaker for 1 h, and adjust the pH to 8 with sodium carbonate , and finally use a 100kD ultrafiltration tube to ultrafilter excess reduced glutathione at a centrifugation rate of 3500 rpm.

[0038] After collecting the filtrate, add hemoglobin aqueous solution (2 mg / mL) under stirring, slowly add 0.5 mL of methanol dropwise under stirring, continue stirring for 0.5 h, then add 200 microliters of manganese tetrasulfonic acid phthalocyanine complex Chloroform solution (1 mg complex), after intermittent ultrasonic crushing in ice bath for 5 minutes, adjust the pH value to weak alkaline with saturated sodium carbonate solution and fully shake until clear, then use 100kD ultrafiltration tube to repeatedly ultrafilter, filter Organic solvents and unreacted small molecules are removed to obtain nanoparticles of hybrid p...

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Abstract

The invention discloses a preparation method and application of an oxygen-carrying hybrid protein loaded metal complex nano-system. The preparation method comprises the following steps: (1) preparinga hybrid protein nano-system; and (2) preparing complex-loaded hybrid protein nano-particles. The invention discloses the preparation method of the hybrid protein loaded metal complex nano-particles,and aims to provide the nano-system which is simple in preparation process, stable in particle size and capable of being used for treating tumors by virtue of oxygen-increasing synergistic SDT. The nano-particles are constructed by virtue of simple self-assembly of a small molecular complex, hemoglobin and albumin, thus, the defects that the metal complex is poor in water solubility and the pure hemoglobin is unstable in oxygen carrying can be overcome, and the hybrid protein system can realize the oxygen-increasing synergistic sonodynamic therapy. The invention provides the application of thehybrid protein loaded complex nano-particles in the aspects of oxygen carrying and sonodynamic therapy. Under the ultrasonic excitation, the complex-hybrid protein system can effectively carry oxygenand also has a sonodynamic anti-tumor effect.

Description

technical field [0001] The invention relates to the technical field of nanometer medicine. Specifically, it is a preparation method and application of an oxygen-carrying hybrid protein-carrying metal complex nanosystem. Background technique [0002] Sonodynamic therapy (SDT) is considered a promising treatment technique for solid tumors due to its ability to deeply penetrate the therapy. However, tumor hypoxia is an important feature of the tumor microenvironment, especially in solid tumors. There is an irreconcilable contradiction between the need to convert sufficient oxygen into singlet oxygen in SDT therapy and the severe hypoxia of tumors, which leads to low therapeutic effect of SDT and becomes one of the main obstacles of SDT therapy. Ultrasound-induced conversion of oxygen into singlet oxygen in SDT further aggravates tumor hypoxia, which in turn leads to severe drug resistance and tumor recurrence, thereby affecting the therapeutic effect. [0003] At present, hy...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K38/42A61K47/64A61P35/00
CPCA61K41/0033A61K38/42A61K47/643A61K47/6445A61P35/00A61K2300/00
Inventor 马爱青刘建强郑明彬尹婷闫冲张丽姗冉慧
Owner GUANGDONG MEDICAL UNIV
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