Phase-transition targeted nanovesicle and preparation method and application thereof

A nanobubble and phase transition technology, which is applied in the field of medicine, can solve the problems of loss of biological activity of targeting factors, poor reproducibility of the preparation process, and poor particle size uniformity, and achieves enhanced ultrasonic imaging, easy large-scale preparation, and stability. good effect

Inactive Publication Date: 2019-07-05
HUBEI UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, these methods have many problems in practical application, such as: it is difficult to obtain nanoscale microbubbles, the obtained microbubbles have large particle size and poor particle size uniformity, poor reproducibility of the preparation process, severe mechanical action and / or Or high temperature may cause targeting factors such as peptides, proteins, antibodies to lose biological activity, etc.

Method used

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  • Phase-transition targeted nanovesicle and preparation method and application thereof
  • Phase-transition targeted nanovesicle and preparation method and application thereof
  • Phase-transition targeted nanovesicle and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Preparation of polylactic acid-folic acid coupling nanobubbles:

[0054] (1) Preparation of polylactic acid copolymer

[0055] Weigh an appropriate amount of recrystallized lactide, add it to a 50mL single-necked round bottom flask, add appropriate amounts of stannous octoate and N-tert-butoxycarbonylethanolamine, vacuum, fill with nitrogen twice, and react at 120°C for 3h under nitrogen protection . The solid formed after the reaction was dissolved in dichloromethane, precipitated in absolute ethanol, and the precipitate was dried in vacuum at room temperature for 24 hours.

[0056] (2) Preparation of polylactic acid-folic acid coupling copolymer

[0057] Dissolve 0.3g polylactic acid copolymer in 10mL CH 2 Cl 2 Among them, 0.088g of folic acid is dissolved in 10mL of anhydrous DMSO. After the two were mixed, 0.041g DCC and 0.1mL triethylamine were added, the reaction was stirred at room temperature for 24h, filtered, and concentrated under reduced pressure to remove most of...

Embodiment 2

[0068] The preparation method is the same as that of Example 1, except that:

[0069] In step (3) (i), the amount of lactic acid-folic acid coupling copolymer is 2g, the amount of perfluoropentane (PFP) is 15g, and the shear rate is 15000rpm;

[0070] In step (3) (iii), the ultrasonic working time is 2s, the interval is 2s, and it is repeated 5 times, and the ultrasonic power is 30w.

Embodiment 3

[0072] The preparation method is the same as that of Example 1, except that:

[0073] In step (3) (i), the amount of lactic acid-folic acid coupling copolymer is 3g, the amount of perfluoropentane (PFP) is 20g, and the shear rate is 20000rpm;

[0074] In step (3) (iii), the ultrasonic working time is 8s, the interval is 8s, and it is repeated 15 times, and the ultrasonic power is 300w.

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PUM

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Abstract

The invention provides a phase-transition targeted nanovesicle and a preparation method and application thereof. The nanovesicle is composed of 1.0-15.0wt% of core filler, 0.1-5.0wt% of a coating material and the balance ultrapure water and is in a sandwiched spherical structure. The core filler is liquid perfluorinated pentane; the coating material is amino terminated polylactic acid. The prepared nanovesicle is milk white and in particle size of 318.4+ / -5.1nm, small in-vitro 3-month particle size change and high stability are realized, ultrasonic imaging effects can be enhanced by the nanovesicle under the action of ultrasonic waves, the nanovesicle can be broken by the ultrasonic waves, and ultrasonic tumor imaging effects can be remarkably improved in a living mouse subcutaneous tumormodel.

Description

Technical field [0001] The content of the present invention belongs to the field of medical technology. It relates to a phase-transition nanobubble and its preparation method and properties. The nanobubble is prepared by the emulsification solvent volatilization method and can be used for ultrasound imaging, MRI imaging diagnosis of tumor lesions and targeted therapy of tumors. It is a new type of integrated diagnosis and treatment. Functional imaging nano-contrast agent. Background technique [0002] Microbubbles are a type of ultrasound imaging contrast agent that can significantly enhance medical ultrasound detection signals. The high acoustic impedance difference between the gas in the microbubbles and the surrounding living tissues makes the microbubbles produce strong reflections, resulting in enhanced backscattering in the blood (in color And spectral Doppler mode can be as high as 27dB), so as to achieve the purpose of enhancing the effect of ultrasound images (JM Correa...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/22A61K49/18A61K49/12A61K45/00A61K9/51A61K47/34A61P35/00
CPCA61K9/5153A61K45/00A61K49/0002A61K49/126A61K49/1857A61K49/223A61P35/00
Inventor 罗斌华王慧丽朱芳银
Owner HUBEI UNIV OF SCI & TECH
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