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Nanometer particle containing elemental gold and application thereof

A nanoparticle and elemental gold technology, which can be applied to medical preparations containing active ingredients, medical preparations without active ingredients, organic active ingredients, etc. Capacitance, high safety effect

Pending Publication Date: 2017-04-26
SHANGHAI NINTH PEOPLES HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The best time for iodine contrast agent is 30s to 70s after injection. After 2 minutes, most of the contrast agent will be excreted through the kidneys. Therefore, after a few minutes or a few hours of scanning, the degree of enhancement has been greatly reduced.

Method used

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  • Nanometer particle containing elemental gold and application thereof
  • Nanometer particle containing elemental gold and application thereof
  • Nanometer particle containing elemental gold and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] A series of gold nanoparticles synthesized using bovine serum albumin (BSA) as a stabilizer, ranging from gold nanoclusters below 2nm to dozens of nanometer-sized particles (J.Mater.Chem.B, 2013, 1, 5045; Nanoscale Research Letters, 2013, 8, 182; Nanoscale 2012, 4(24), 7766), to gold nanospheres of a few hundred nanometers or even several micrometers in size.

[0041] Mix 10ml of 5mg / ml BSA solution with 1ml of 10nM chloroauric acid, add 20mg of ascorbic acid, and stir for 30 minutes at room temperature. When the color of the solution changes from yellow to colorless and then to purple-blue, it indicates Au -BSA nanoparticle formation.

[0042] Observed by TEM and HRTEM, the obtained nanometers can have monodispersion and homogeneity, with narrow particle size distribution, with a median value of 50nm (see Figure 1A ). Magnify the TEM image, you can further observe the shape of the nanoparticles presenting a flower-like 3D structure. Figure 1B It can be seen that the gray ...

Embodiment 2

[0045] Example 2 Preparation of Au-BSA-DOX particles

[0046] Using the prepared Au-BSA nanoparticles as a carrier, doxorubicin (DOX) is bound to the nanoparticles. The method is as follows:

[0047] 5mg cis-aconitic anhydride (cis-aconitic anhydride) was dissolved in 200μL 1,4-dioxane, and slowly added DOX solution (7mg DOX dissolved in 4ml water), after stirring, adjust the pH to 9.0, In an ice bath for 20 minutes. After that, the pH was adjusted to 7.0 and stirring was continued for 30 minutes to combine cis-3-carboxyglutaenedioic acid anhydride with DOX (cis-DOX). Centrifuge at 8,000 rpm for 10 minutes to separate and obtain a precipitate.

[0048] The precipitate was dissolved in water containing 7mg EDCl and 3mgN succinimide (NHS). After stirring for 4 hours in the dark, Au-BSA nanoparticles (100mg) were added. After stirring for 16 hours, the mixture was separated on Sephadex G-25. Au-BSA nanoparticles of DOX (denoted as: Au-BSA-DOX).

Embodiment 3

[0049] Example 3 Binding of folic acid to Au-BSA-DOX

[0050] Folic acid (FA) is bound to Au-BSA-DOX through an amide bond. The method is:

[0051] Add 2mg NHS and 3mg EDCl to the DMSO solution of FA, and stir for 4 hours in the dark at room temperature, then add 3ml of Au-BSA-DOX solution at a concentration of 50mg / mL, and stir for 10 hours in the dark, in Sephadex G-25 Au-BSA nanoparticles (denoted as: Au-BSA-DOX-FA) that bind DOX and FA are separated.

[0052] The binding efficiency of DOX and FA with Au-BSA nanoparticles was measured by ultraviolet-visible light waves, and it was determined that there were characteristic absorptions at 360nm (FA) and 495nm (DOX), and the characteristic absorption of Au-BSA nanoparticles was 280nm.

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Abstract

The invention relate to a nanometer particle containing elemental gold. The nanometer particle is characterized by comprising nanometer crystal clusters formed by the elemental gold. The elemental gold has the 2[theta] measuring feature peak mainly at 38.2 degrees in an X-ray powder diffraction spectrum, and 2[theta] measuring feature peaks at 44.3 degrees, 64.7 degrees, 77.7 degrees, 82.0 degrees and the like. The nanometer particle provided by the invention belongs to the nanometer particle below 100nm; in addition, the particle diameter distribution is narrow; the nanometer particle realizes the long-period stable suspension in a solution state without sedimentation for at least one month (partial samples realize the stable state maintaining for 12 months); and the nanometer particle is suitable to be used for in vivo X-ray or CT (Computed Tomography) imaging detection as a contrast agent.

Description

Technical field [0001] The invention relates to a method for preparing a composite material, in particular to a gold nanocomposite material wrapped by protein, and a preparation method. Background technique [0002] Contrast agent, also known as contrast agent, is a chemical product injected (or taken) into human tissues or organs to enhance the observation effect. The density of these products is higher or lower than the surrounding tissues, thus forming a sharp contrast, which greatly improves the discrimination of the target tissue and surrounding tissues by the CT imaging system. At present, the most commonly used CT contrast agents in clinical practice are iodine-based small molecule compounds, including ionic and non-ionic, such as: iohexol (Omnipaque), lopanoic acid (lopanoic acid) and diatrizoic acid (Diatrizoic acid), etc. , This is because iodine has a higher atomic number and produces stronger absorption of X-rays. However, these traditional small-molecule iodine con...

Claims

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Application Information

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IPC IPC(8): A61K49/04A61K47/02A61K47/64A61K47/69A61K31/704A61P35/00
CPCA61K31/704A61K47/02A61K49/04
Inventor 王贤松张文杰黄鹤
Owner SHANGHAI NINTH PEOPLES HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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