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A sound-controlled nanoparticle-loaded berberine release system and its preparation method and application

A nanoparticle and release system technology, applied in the preparation of drug carriers, sonosensitizer carrier, sound-controlled nanoparticle-loaded berberine release system and its preparation, application fields in sonosensitizers, can solve the problems that have not yet been used Acoustic-controlled nano drug-loaded release system, sonosensitizer carrier, etc.

Active Publication Date: 2018-09-14
HARBIN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In the experiment of sonodynamic therapy research, there is no research using the sound-controlled nano drug delivery system as the carrier of the sonosensitizer

Method used

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  • A sound-controlled nanoparticle-loaded berberine release system and its preparation method and application
  • A sound-controlled nanoparticle-loaded berberine release system and its preparation method and application
  • A sound-controlled nanoparticle-loaded berberine release system and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Example 1 Construction method of a sound-controlled nanoparticle drug-loaded release system

[0055] (1) Synthesis of upconversion nanoparticle cores (sodium yttrium fluoride nanoparticles)

[0056] Yttrium chloride hexahydrate (0.237mg, 0.78mmol), ytterbium chloride hexahydrate (0.0775mg, 0.2mmol), and erbium chloride hexahydrate (0.0077mg, 0.02mmol) were added together in a 250mL three-neck round bottom flask, Then oleic acid (6 mL) and octadecene (5 mL) were added to obtain a mixture; under argon, the mixture was stirred and heated to 160° C. for 30 min, then 10 mL of octadecene was added, and the mixture was kept stirring at 160° C. After 1h, it was naturally cooled to 50°C; at this time, a solution of ammonium fluoride (148.16mg, 4mmol) and sodium hydroxide (100mg, 2.5mmol) dissolved in methanol (10mL) was added to the mixture, kept at 50°C and stirred for 30min to nucleate, then Distill the methanol at 70°C; heat the mixture rapidly to 300°C and keep it under mag...

Embodiment 2

[0070] Example 2 In vitro drug release of sound-controlled nanoparticle drug-loaded delivery system

[0071] Figure 5 It is a schematic diagram of the sound-controlled release of the targeted drug delivery system; among them, A is the mechanism of action of the "singlet oxygen sensitive switch", and the singlet oxygen ( 1 o 2 ) to oxidize the carbon-carbon double bond of the compound shown in formula I to form an unstable quadruple ring, the quadruple ring is broken, and the singlet oxygen sensitive switch is cut off, thereby releasing the drug; Figure B shows the sound-controlled release of the targeted sound-controlled drug delivery system, Silicon dioxide (SiO 2 ) coated upconverting nanoparticles, NH 2 Group modified SiO 2 , bonded to a singlet oxygen sensitive switch (compound shown in formula Ⅰ), physically adsorbed berberine, and linked hyaluronic acid through the -COOH group of the compound shown in formula Ⅰ to form a targeted drug-loading system. When berberine...

Embodiment 3

[0074] Example 3 Drug safety experiment of sound-controlled nanoparticle drug-loaded release system

[0075] Inject nanoparticles into mice grouped with different doses through the tail vein, the doses are 25mg / kg, 50mg / kg, and 100mg / kg, and observe after one week. The observation results show that: low dose, medium dose, high dose, control group There were no obvious abnormalities in the growth activities and appearance characteristics of the mice in the 4 groups, and no obvious abnormalities could be seen in the hearts, livers and kidneys after dissection ( Figure 8 shown). It shows that the synthesized sound-controlled nanoparticle-loaded berberine complex drug has high safety and can be used in clinical research.

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Abstract

The invention discloses a sound-control nanoparticle-loaded berberine releasing system and a preparation method and application thereof. The sound-control nanoparticle-loaded berberine releasing system comprises upconversion nanoparticles which are amino-modified in surfaces and clad through SiO2, a singlet oxygen sensitive switch, hyaluronic acid and berberine; one end of the singlet oxygen sensitive switch is coupled to the upconversion nanoparticles which are amino-modified in surfaces and clad through SiO2 through amido bonds, the other end of the singlet oxygen sensitive switch is coupled to the hyaluronic acid through ester bonds, the berberine is loaded in the upconversion nanoparticles which are amino-modified in surfaces and clad through SiO2 in a wrapped or covalent linkage mode, and the berberine releases singlet oxygen under the ultrasonic action, so that a carbon-carbon double bond in the singlet oxygen sensitive switch is ruptured, the berberine is released, and aggregation of medicine in non-target tissues can be reduced. Raising of the sound-control nanoparticle-loaded berberine releasing system fills up the blank of sound-sensitive agent carriers in SDT research, and application of a sound-control nanoparticle drug loading system to SDT is achieved.

Description

technical field [0001] The present invention relates to a sonodynamic therapy carrier of a sonosensitizer, in particular to a sound-controlled nanoparticle-loaded berberine release system and its preparation method, and its application in the preparation of a sonodynamic therapy for atherosclerosis And the application in the preparation of drug carrier. The invention belongs to the technical field of the combination of sound-controlled drug release and nanomedicine. Background technique [0002] Sonodynamic Therapy (SDT) is a new non-invasive treatment method firstly proposed by Japanese scholar Umemura et al. in 1989 on the basis of photodynamic therapy. Compared with photodynamic therapy, the ultrasound used in sonodynamic therapy has a low attenuation coefficient and strong penetrating ability in tissues, activates the sound sensitizer accumulated in the target tissue to generate active oxygen, and produces a series of biological reactions. No tissue damage. The choice...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61K9/51A61K31/4375A61K47/36A61K47/02A61K47/20A61K47/61A61K47/54A61P9/10
CPCA61K9/5115A61K9/5123A61K9/5161A61K31/4375A61K41/0028A61K47/02A61K47/20A61K47/36
Inventor 杨力明田野朱兴寇佳媛郑龙彬李雪松
Owner HARBIN MEDICAL UNIVERSITY
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