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Compound nano-diagnosis preparation and preparation method of same

A preparation and nanotechnology, applied in the field of biomedicine, can solve the problems of high nuclear magnetic sensitivity and spatial resolution, inability to be dynamic, real-time imaging, low sensitivity and resolution, etc., to improve diagnostic efficiency, water solubility and biocompatibility. Good and broad application prospects

Active Publication Date: 2017-12-22
THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] Ultrasound, photoacoustic, and nuclear magnetic imaging are currently the most widely used molecular imaging diagnostic methods in scientific research. Each has its own advantages. The rate is low; photoacoustic imaging has the advantage of deep penetration, but the acoustic signal is weak; nuclear magnetic sensitivity and spatial resolution are large, but the time resolution is poor, and dynamic and real-time imaging cannot be performed

Method used

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  • Compound nano-diagnosis preparation and preparation method of same
  • Compound nano-diagnosis preparation and preparation method of same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] (1) Preparation process of DMPE-DTPA-Gd:

[0038] Dissolve 1,2-tetradecanoylphosphatidylethanolamine (DMPE) in chloroform to prepare 4 mL of a solution with a concentration of 0.1 mM. Add 30 μL of triethylamine dropwise to 20 mL of 1 mM diethyltriaminepentaacetic acid (DTPA) dissolved in dimethylsulfoxide (DMSO) and add the crosslinker 1-(3-dimethylaminopropyl base)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). The above two solutions were mixed and incubated at room temperature in an argon atmosphere for 3 h, then dialyzed in DMSO solution for 12 h (dialysis bag: MW 3500), and then dialyzed in ultrapure water for 48 h. The prepared DMPE-DTPA was lyophilized and stored.

[0039] Accurately weigh 0.384 g DMPE-DTPA, dissolve in 10 mM sodium acetate buffer solution with pH=5.8, then add 0.337 mM GdCl 3 3.1 mL of aqueous solution, the pH of the solution was adjusted to 6.5 with 1 M NaOH, and then heated at 50 °C for 5 h. After the reaction was...

Embodiment 2

[0045] The Gd content in the Hybrid liposome composite nanoemulsion in Example 1 is detected by ICP-MS, and the original sample is diluted to a certain concentration gradient (0.01 mM / L, 0.02 mM / L, 0.04 mM / L, 0.04 mM / L, 0.06mM / L, 0.08 mM / L, 0.1 mM / L), and perform MRI imaging on the MRI system. The result is as image 3 As shown, with the increase of the concentration of Hybrid liposome composite nanoemulsion, the enhancement effect of T1 contrast becomes more and more obvious. According to the quantitative fitting results, it can be judged that when the concentration of the composite nanoemulsion reaches 100 μg / mL, the NMR image shows that the relaxation time T1 is significantly reduced. The shorter the relaxation time T1 and the larger the relaxation rate r1, the stronger the contrast ability of the material. Compared with the commercial MRI contrast agent gadopentetate dimeglumine, its relaxation rate is 3-4 times that of the commercial contrast agent. It can be seen that...

Embodiment 3

[0047] After diluting the Hybrid liposome composite nanoemulsion and free IR-780 in Example 1 to a certain concentration (distilled water was used as a blank control), it was detected by a UV-spectrophotometer to obtain a UV-visible absorption spectrum. Such as Figure 4 As shown, pure IR-780 and Hybrid liposome composite nanoemulsion have strong near-infrared absorption in the near-infrared range of 790 nm-770. After being coated with menthol and phospholipids, the longitudinal absorption peak has a slight blue shift. This is because the surrounding menthol and phospholipid spherical cavity changes the refractive index of the medium, which causes the resonance absorption wavelength to blue shift. The above results show that the Hybrid liposome composite nanoemulsion well retains the optical absorption properties of IR-780.

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Abstract

The invention discloses a compound nano-diagnosis preparation and a preparation method of same. The compound nano-diagnosis preparation is prepared by coating menthol and IR-780 iodide with a lipid carrier comprising: phospholipid, cholesterol, and dimyristoyl phosphoethanolamine-diethyl triamine pentaacetic acid-gadolinium. The particle size of the compound nano-diagnosis preparation is 90-2000 nm. The compound nano-diagnosis preparation integrates ultrasonic / opto-acoustic / nuclear magnetic resonance imaging and photo-thermal therapy function, wherein by combining multi-modal imaging with the photo-thermal therapy, reliable image evidence is supplied to photo-thermal therapy through the multi-modal imaging, thus increasing time, spatial selectivity and accuracy of the photo-thermal therapy. In addition, due to the characteristic EPR effect of nano-scale, the compound nano-diagnosis preparation is easy to enrich at a tumor lesion, so that not only is diagnosis efficiency increased but also the risk of toxic and side effects on a patient is reduced, thereby accelerating the progress of integration of the multi-modal imaging with the photo-thermal therapy.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a composite nano-diagnosis and treatment preparation and a preparation method thereof. Background technique [0002] In recent years, cancer has seriously threatened human health. Accurate diagnosis and effective treatment of cancer have been hot and difficult research topics in this field for a long time. In clinical practice, tumor diagnosis and treatment are still two relatively independent processes. The separate use of diagnostic reagents and therapeutic drugs prolongs the cycle of disease diagnosis and treatment, resulting in a high risk of delaying the disease and increasing the economic burden of patients. Relying on the rapid development of nanotechnology, the integrated preparation of diagnosis and treatment is widely used in the biomedical field due to its good biomembrane penetration, high permeability and retention effect (EPR effect) of passively targeting solid tumors, ...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K31/045A61K49/18A61K49/22A61K49/00A61K9/127A61P35/00
CPCA61K9/127A61K31/045A61K41/0052A61K49/0002A61K49/1812A61K49/227
Inventor 谢晓燕张春阳
Owner THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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