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Method for increasing dispersion stability of nanoparticles as T1 MRI contrast agent and T1 MRI contrast agent nanoparticles

A technology of dispersion stability and nano-particles, which is applied in the direction of nuclear magnetic resonance/magnetic resonance imaging contrast agents, pharmaceutical formulations, preparations for in vivo tests, etc. spin, low surface area-to-volume ratio effects, etc.

Active Publication Date: 2018-10-26
INVENTERA PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Currently, metal chelate-like materials commonly used as T1-type contrast agents cannot effectively relax the hydrogen nuclear spins in water molecules due to their small size-induced tumbling rate.
On the other hand, in the case of metal oxide-based nanoparticles, which have slower molecular motion rates compared to metal chelates, and can relax nuclear spins synergistically by various metals, but due to the low surface-to-volume ratio However, its effect is limited

Method used

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  • Method for increasing dispersion stability of nanoparticles as T1 MRI contrast agent and T1 MRI contrast agent nanoparticles
  • Method for increasing dispersion stability of nanoparticles as T1 MRI contrast agent and T1 MRI contrast agent nanoparticles
  • Method for increasing dispersion stability of nanoparticles as T1 MRI contrast agent and T1 MRI contrast agent nanoparticles

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0102] Example 1: Synthesis of dextran nanocarriers and partial coating of T1-type contrast materials

[0103] Dextran nanocarriers were synthesized by crosslinking of dextran (molecular weight of 10 kDa, Pharmacosmos, Denmark). Specifically, after dissolving 1.8 g of dextran in an alkaline aqueous solution, epichlorohydrin (6 mL of epichlorohydrin, Sigma, USA) and ethylenediamine (26 mL of ethylenediamine, Sigma, USA) were added as a crosslinking agent. ), at room temperature, reacted 24 hours in a constant temperature tank. Reactants were purified using hollow fiber membrane filters (MWCO 10000, GE Healthcare, Netherlands). The synthesized dextran nanocarriers exhibited a hydrodynamic diameter of about 4.1 nm. FeCl2, FeCl3 and NaOH were added to the synthesized dextran nanocarrier at a ratio of 1:2:8 mol, and stirred under strong magnetic force at room temperature for 30 minutes, and Fe3O4 was introduced into the T1 contrast material. Synthesized nanoparticles were purifi...

Embodiment 2

[0104] Embodiment 2: the ratio adjustment of the T1 type contrast material attached to the dextran nanocarrier

[0105] In the introduction step of the T1 type contrast material in the above-mentioned embodiment 1, when the weight (weight) of the total dextran nanocarrier is 100, the amount of the T1 type contrast material (FeCl2, FeCl3) (based on Fe metal) Adjusted to the following 0.1% (wt), 1% (wt), 2.5% (wt), 5.0% (wt), 10.0% (wt), 25% (wt), 50% (wt) and 100% (wt ), thereby adjusting the percentage of T1-type contrast material attached to the dextran nanocarriers. The hydrodynamic diameters of the synthesized nanoparticle contrast agents were determined to be about 4.7 nm, 4.8 nm, 5.8 nm, 6.5 nm, 7.2 nm, 9.0 nm, 10.0 nm, and 25 nm, respectively, with increasing amounts of T1-type contrast material. Quantification of T1-type contrast material attached to dextran nanocarriers was performed using an inductively coupled plasma mass spectrometer (ICP-MS, PerkinElmer, USA). Sp...

Embodiment 3

[0106] Embodiment 3: the quantification of the hydrophilic functional group on the nanocarrier surface

[0107] Amine (-NH2) functional groups were introduced into the surface of the nanocarriers prepared in Example 1 above, so for the quantification of the hydrophilic functional groups on the surface of the nanocarriers, TNBSA assay, a well-known quantitative method for amines, was used. Specifically, 0.25 mL of 0.01% (w / v) TNBSA (2,4,6-Trinitrobe nzenesulfonic Acid, Thermo, USA) aqueous solution was added to 0.5 mL of nanocarriers at a concentration of 10 mg / mL, and heated at 37° C. After reacting at temperature for 2 hours, 0.25 mL of 10% SDS (sodium dodecyl sulfate, Sigma, USA) aqueous solution and 0.125 mL of 1M HCl (Sigma, USA) were added, and the absorbance was measured at a wavelength of 339 nm. At this time, in order to quantify the amount of amine groups by absorbance, five different concentrations of lysine (Lysine) (Sigma, USA) solutions were measured using TN BSA ...

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Abstract

The present invention improves an existing contrast agent, especially, a T1 contrast agent, and adopts a strategy in which the T1 contrast material is partially coated on a support surface to which ahydrophilic functional group is exposed. The partial coating strategy adopted in the present invention improves both the stability and contrast performance of T1 contrast agent nanoparticles, and sucha strategy leads to very interesting technical development.

Description

technical field [0001] This patent application claims priority to Korean Patent Application No. 10-2016-0019363 filed at the Korean Patent Office on February 18, 2016, the disclosure of which is incorporated herein by reference. [0002] The invention relates to a method for improving the dispersion stability of nanoparticles used as a T1-type magnetic resonance imaging contrast agent and the nanoparticles of the T1-type magnetic resonance imaging contrast agent. Background technique [0003] Nanomaterials (nanomaterials) exhibit new physical / chemical properties different from granular materials (bulkmaterials) due to size reduction. And, not only the size of the material but also the composition and shape of the material can be adjusted due to many studies on nanomaterials, so that excellent physical / chemical properties can be achieved in the nano field. Nanotechnology is currently being developed in various ways and is divided into three main areas. First, technologies i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/18A61K49/06A61K49/08
CPCA61K49/1878A61K49/1863A61K2123/00
Inventor 千珍宇申泰铉
Owner INVENTERA PHARM INC
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