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Porphyrin-selenide-adriamycin composite nanoparticles as well as preparation method and application thereof

A technology of composite nanoparticles and doxorubicin, which is applied in the direction of nanotechnology, nanotechnology, nanomedicine, etc., can solve the problems of failure to achieve therapeutic effect, liver function damage, and clinical application limitations, and achieve superior photothermal performance and reduce Toxic and side effects, the effect of achieving specific release

Active Publication Date: 2022-03-01
NANJING GENERAL HOSPITAL NANJING MILLITARY COMMAND P L A
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In addition, the adverse reactions of DOX include phlebitis, skin pigmentation, liver function damage, etc., and the clinical application is greatly limited.
Moreover, due to the non-targeting nature of the drug itself, there will be no difference in the distribution in the human body, the utilization rate is low, and the ideal therapeutic effect cannot be achieved.

Method used

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  • Porphyrin-selenide-adriamycin composite nanoparticles as well as preparation method and application thereof
  • Porphyrin-selenide-adriamycin composite nanoparticles as well as preparation method and application thereof
  • Porphyrin-selenide-adriamycin composite nanoparticles as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1 Preparation of Porphyrin-Selenide-Adriamycin Composite Nanoparticles

[0046] Step a) dissolving doxorubicin hydrochloride in water to obtain an aqueous solution of 1 mg / mL doxorubicin hydrochloride;

[0047] Step b) Weighing 5,10,15,20-tetrakis(4-aminobenzene)-21H,23H-porphyrin (0.338g, 0.5mmol), purchased from Jiangsu Aikang Biopharmaceutical Research and Development Co., Ltd., diselenide ( 0.368g, 1mmol), dissolved in 30mL of 1,4-dioxane solution, placed in a high-temperature glass tube, ultrasonically reacted for 30min, and air-sealed after three freezing pump-thawing cycles. After the reaction tube was reacted at a constant temperature of 120° C. for 24 hours, the hydrothermal reaction was completed. Cooled and opened, the purple product was isolated by filtration. During further purification, the purple unreacted product was eluted with tetrahydrofuran (THF), and the porphyrin-selenoether porous organic polymer was obtained after further vacuum drying;...

Embodiment 2

[0050] Example 2 Research on Morphological Characteristics and Characterization of Porphyrin-Selenide Porous Organic Polymer and Porphyrin-Selenide-Adriamycin Composite Nanoparticles

[0051] The porphyrin-selenoether porous organic polymer prepared in step b) of Example 1 and the porphyrin-selenoether-doxorubicin nanoparticles prepared in step d) of Example 1 were subjected to morphological research. The morphology was observed by transmission electron microscopy (TEM) at room temperature ( figure 1 ).

[0052] The infrared absorption spectrum of the samples was detected by the potassium bromide tablet method. Grind porphyrin-selenoether-doxorubicin polymer, doxorubicin, porphyrin-selenoether-doxorubicin nanoparticle solid powder with potassium bromide powder respectively, take 1-2mg sample and add 100-200mg bromine Potassium chloride is ground into a fine powder in an agate mortar, and the sample is continuously scraped to the center of the mortar with a small stainless st...

Embodiment 3 Embodiment 1

[0057] The porphyrin-selenoether-doxorubicin composite nanoparticle encapsulation efficiency, the mensuration of drug loading amount that embodiment 3 embodiment 1 makes

[0058] (1) Weigh an appropriate amount of doxorubicin reference substance, and after dissolving in distilled water, the ultraviolet spectrophotometer scans at 200-800 nm to obtain the maximum absorption wavelength at 483 nm.

[0059] (2) Drawing of standard curve

[0060] Prepare 0.5 g / L doxorubicin hydrochloride standard solution stock solution with distilled water. Obtain standard solutions with mass concentrations of 5.0, 10.0, 20.0, 30.0, 40.0, and 50.0 μg / L for the test solution. Measure the absorbance (A) value of different mass concentration doxorubicin hydrochloride test solution respectively at 483nm wavelength place, carry out linear regression to mass concentration with A value, regression equation is A=0.0179C+0.0167(R 2 =0.9998, n=3), the linear relationship is good.

[0061] (3) Determinatio...

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Abstract

The invention relates to a preparation method and application of a photo-thermal nano preparation for chemical-photo-thermal-chemical kinetics combined tumor therapy, and the method comprises the following steps: firstly, obtaining a porphyrin porous covalent organic polymer through a hydrothermal reaction, encapsulating adriamycin in the porphyrin porous covalent organic polymer to obtain a photosensitive material, and then preparing the photo-thermal nano preparation. Through passive targeting of specific environment-sensitive covalent bonds existing in the porous covalent polymer, the blood circulation time can be effectively prolonged, and effective enrichment at the tumor site can be realized. After reaching the tumor tissue, the porous organic polymer absorbs the energy of the laser and converts the energy into heat energy under the irradiation of the laser, then the photosensitive porous organic polymer accelerates the release of the chemotherapeutic drug adriamycin, and meanwhile, the diselenide bond is reduced by GSH overexpressed by tumor cytoplasm to generate reactive oxygen species (ROS); therefore, photothermal therapy-chemotherapy-chemical kinetics combined tumor therapy is realized.

Description

technical field [0001] The invention relates to the technical field of biopharmaceuticals, in particular to a composite nanoparticle of porphyrin-selenoether-doxorubicin and its preparation method and application. Background technique [0002] Targeted drugs (also referred to as targeting agents) refer to drugs or their preparations endowed with targeting capabilities. Its purpose is to enable the drug or its carrier to target a specific lesion site, and accumulate or release active ingredients at the target site. Targeted preparations can make the drug form a relatively high concentration in the target area, thereby improving the efficacy of the drug while inhibiting toxic side effects and reducing damage to normal tissues and cells. [0003] Near-infrared photothermal therapy agent refers to the use of reagents with high photothermal conversion efficiency in the near-infrared region, injecting them into the interior of organisms through blood vessels, using targeted recog...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K31/704A61K41/00A61P35/00B82Y5/00B82Y30/00B82Y40/00
CPCA61K31/704A61K41/0071A61K41/0052B82Y5/00B82Y30/00B82Y40/00A61K47/6935A61P35/00A61K2300/00
Inventor 宋勇周宝龙谭薇吕镗烽娄晗
Owner NANJING GENERAL HOSPITAL NANJING MILLITARY COMMAND P L A
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