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Eumelanin-like nano contrast agent loaded with therapeutic drug and synthesis method thereof

A nano-contrast agent, therapeutic drug technology, applied in drug combination, nanotechnology for sensing, drug delivery, etc. to avoid safety problems, great clinical translation value, and simple synthesis method

Active Publication Date: 2022-08-09
中国人民解放军陆军特色医学中心
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, translation of many nanodrug delivery systems to clinical applications has been hampered by high cost, low biocompatibility and biodegradability, and poor loading efficiency.

Method used

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  • Eumelanin-like nano contrast agent loaded with therapeutic drug and synthesis method thereof
  • Eumelanin-like nano contrast agent loaded with therapeutic drug and synthesis method thereof
  • Eumelanin-like nano contrast agent loaded with therapeutic drug and synthesis method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] A method for synthesizing a therapeutic drug-loaded eumelanin-like nano-contrast agent, comprising the following steps:

[0049] 1) 20mg of dopamine hydrochloride (mass concentration is 0.5mg / mL) is dissolved in 40mL of deionized water, then placed in a water bath with a temperature of 30 ° C and stirred to obtain a dopamine hydrochloride solution;

[0050] 2) Under the condition of vigorous stirring (stirring speed is 1200rpm), quickly (within 1min) 100 μL of manganese chloride tetrahydrate (mass concentration is 10mg / mL) dispersed by ultrasonic is added to the above-mentioned dopamine hydrochloride solution, and then at temperature Continue stirring for 1.5 hours in a water bath at 30°C to obtain a mixed suspension of dopamine hydrochloride and metal salt ions;

[0051] 3) Quickly (within 1min) add 10 mL of Tris aqueous solution (molar concentration of 100 mmol / L) to the mixed suspension obtained in step 2), and then maintain the reaction in a water bath with a temper...

Embodiment 2

[0054] A method for synthesizing a therapeutic drug-loaded eumelanin-like nano-contrast agent, comprising the following steps:

[0055] 1) 20 mg of dopamine hydrochloride (mass concentration is 0.5 mg / mL) is dissolved in 40 mL of deionized water, then placed in a water bath with a temperature of 37 ° C and stirred to obtain a dopamine hydrochloride solution;

[0056] 2) Under the condition of vigorous stirring (stirring speed is 1200rpm), quickly (within 1min) 179 μL of manganese chloride tetrahydrate (mass concentration is 10mg / mL) dispersed by ultrasonic is added to the above-mentioned dopamine hydrochloride solution, and then at temperature Continue stirring for 1.0 hours in a water bath at 37°C to obtain a mixed suspension of dopamine hydrochloride and metal salt ions;

[0057] 3) Quickly (within 1min) add 10 mL of Tris aqueous solution (molar concentration of 100 mmol / L) to the mixed suspension obtained in step 2), and then maintain the reaction in a water bath with a tem...

Embodiment 3

[0060] A method for synthesizing a therapeutic drug-loaded eumelanin-like nano-contrast agent, comprising the following steps:

[0061] 1) 20 mg of dopamine hydrochloride (mass concentration is 0.5 mg / mL) is dissolved in 40 mL of deionized water, then placed in a water bath with a temperature of 40 ° C and stirred to obtain a dopamine hydrochloride solution;

[0062] 2) Under the condition of vigorous stirring (stirring speed is 1200rpm), quickly (within 1min) 300 μL of manganese chloride tetrahydrate (mass concentration is 10mg / mL) dispersed by ultrasonic is added into the above-mentioned dopamine hydrochloride solution, and then at temperature Continue stirring for 0.5 hours in a water bath at 40°C to obtain a mixed suspension of dopamine hydrochloride and metal salt ions;

[0063] 3) Quickly (within 1min) add 10 mL of Tris aqueous solution (molar concentration of 100 mmol / L) to the mixed suspension obtained in step 2), and then maintain the reaction in a water bath with a t...

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Abstract

The invention discloses a synthetic method of a eumelanin-like nano contrast agent loaded with a therapeutic drug, which comprises the following steps: firstly, polymerizing metal salt ions as a manganese source and dopamine hydrochloride as precursor molecules to form manganese-eumelanin nano particles, and then loading a targeted drug on the manganese-eumelanin nano particles to obtain the eumelanin-like nano contrast agent. The invention also discloses an application of the eumelanin-like nano contrast agent loaded with the therapeutic drug. The eumelanin-like nano contrast agent provided by the invention has high metal loading capacity and geometric confinement effect, and shows excellent T1-T2 dual-mode MRI contrast enhancement capability; meanwhile, a neuroprotective agent curcumin is loaded on angiopep-2 functionalized and manganese-doped eumelanin nanoparticles to prepare antioxidation and anti-neuroinflammation for targeted diagnosis and treatment of traumatic brain injury and AMEC accumulated at a traumatic part, so that a long-term treatment effect on secondary brain injury is realized; the AMEC well combines a drug carrier with medical imaging, and has good clinical application potential.

Description

technical field [0001] The invention belongs to the technical field of medical preparations, in particular to an eumelanin-like nano-contrast agent loaded with therapeutic drugs and a synthesis method thereof. Background technique [0002] Traumatic brain injury (TBI) has become a major public health problem worldwide with high morbidity and mortality rates. It is a complex process consisting of primary and secondary brain damage. Primary brain injury is associated with external shocks, and secondary brain injury is caused by excess production of reactive oxygen species (ROS) and leads to multiple TBI-related brain injuries. In the microenvironment of brain injury, excess ROS can activate inflammatory and immune responses by stimulating the expression of cytokines, causing further damage of inflammation and ultimately neurological deficits. In addition, a large number of activated astrocytes and microglia are recruited to the injured area, inhibiting neuronal regeneration,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/00A61K49/22A61K49/12A61K49/18A61K31/12A61K31/785A61K47/64A61P25/00A61P29/00A61P39/06B82Y5/00B82Y15/00
CPCA61K49/0002A61K49/221A61K49/225A61K49/126A61K49/1857A61K31/12A61K31/785A61K47/64A61P25/00A61P29/00A61P39/06B82Y5/00B82Y15/00A61K2300/00Y02A50/30
Inventor 陈晓刘凯军刘恒方靖琴孙多王毅刘玉
Owner 中国人民解放军陆军特色医学中心
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