Calcium ion nano chelating agent as well as preparation method and application thereof

A technology of calcium ion chelating agent and chelating agent, which is applied in the direction of non-effective ingredients of polymer compounds, drug combinations, and pharmaceutical formulations, and can solve problems such as small molecular weight of chelating agents, slow down the biochemical reaction of metalloenzymes, and the lack of metal ions, etc., to achieve Strong calcium ion chelation performance, avoid irreversible damage, and inhibit tumor growth

Active Publication Date: 2022-05-20
UNIV OF SCI & TECH OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, adverse reactions such as edema, flushing, headache, dizziness, and drowsiness may occur after the use of calcium channel blockers, and they have little effect on the chelation of calcium ions in cells.
[0004] Existing calcium ion chelating agents such as: ethylenediaminetetraacetic acid or ethylene glycol ditetraacetic acid will also chelate divalent metal ions such as magnesium ions, manganese ions, and ferrous ions while chelating calcium ions. The selectivity to calcium ion chelation is low, and it is easy to cause side effects of other metal ion deficiency, such as: anemia, brain and heart disease, growth retardation, slowing down the biochemical reactions catalyzed by metalloenzymes and causing metabolic disorders
While 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetra(acetoxymethyl ester) (BAPTA-AM) is a cell-permeable calcium chelator, entering Cells can be hydrolyzed by esterase to become active calcium chelator BAPTA, and then selectively bind to Ca 2+ Rapid pairing, thereby reducing the intracellular calcium concentration, but due to its poor water solubility, high accumulation in the kidney and liver, and poor penetration and retention in tumors, the clinical treatment effect is not good, and it also causes irreversible damage to normal tissues. damage, which hinders its wide application in the body, and the molecular weight of the above-mentioned chelating agent is small, and it is easy to be degraded before it can play a role
In order to improve the ability of calcium ion chelation, there are also studies using nanocarriers (liposomes, polymer micelles, etc.) to deliver calcium ion chelating agents to tumors to interfere with calcium metabolism in tumors; Non-specific, it will also adsorb other metal ions while adsorbing calcium ions; on the other hand, there is no guarantee that the calcium chelator will be released and function at the tumor site

Method used

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  • Calcium ion nano chelating agent as well as preparation method and application thereof
  • Calcium ion nano chelating agent as well as preparation method and application thereof
  • Calcium ion nano chelating agent as well as preparation method and application thereof

Examples

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Effect test

Embodiment 1

[0052] Embodiment 1 A kind of preparation method of calcium ion nano-chelating agent

[0053] The schematic diagram of this embodiment is as figure 1 , the preparation method comprises the following steps carried out in sequence:

[0054] S0: Preparation of carboxyl-functionalized calcium ion chelating agent

[0055] With 9kg of 5-methyl-2-nitrophenol (compound 1,59mol) and 4.9kg of K 2 CO 3 (35mol) was dispersed in 24L of anhydrous N,N-dimethylformamide, stirred at 90°C for 20min; 66kg of 1,2-dibromoethane (351mol) was added until the bright orange color of the above mixture faded quickly It is pale yellow with white precipitates, continue to react at 90°C for 18h; after cooling to room temperature, filter the precipitate and filtrate, wash the precipitate with water and dichloromethane in sequence, and dilute the filtrate and precipitate washing solution with a concentration of 0.1M The NaOH solution was washed repeatedly until the orange color no longer appeared in the ...

Embodiment 2～7

[0072] The preparation method of embodiment 2~7 calcium ion nano-chelating agent

[0073] Embodiment 2~7 is respectively a kind of preparation method of calcium ion nano-chelating agent, and the processing step in their preparation method is similar to embodiment 1, and the difference with embodiment 1 is only:

[0074] In Example 2, the molar ratio of acrylamide, 2-methacryloyloxyethylphosphorylcholine and the double acrylated matrix metalloproteinase-responsive polypeptide whose amino acid sequence is GGVPMSMRGGK is 5:5:1; the calcium ion chelating agent The mass ratio of polymer to mercapto-PEG-acrylamide is 0.25:1; wherein, the molecular weight of PEG in the mercapto-PEG-amino polymer is 7500Da; the concentration of gold nanoparticles in the aqueous solution containing gold nanoparticles is 10mg / mL; In step S2, the reaction time is 18 hours; the obtained calcium ion nano-chelating agent is marked as M2.

[0075] In Example 3, the molar ratio of acrylamide, 2-methacryloylo...

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Abstract

The invention discloses a calcium ion nano chelating agent and a preparation method and application thereof.The calcium ion nano chelating agent is of a core-shell structure, an inner core is gold particles containing a sulfydryl structure and modified by 1, 2-bis (2-aminophenoxy) ethane-N, N, N ', N'-tetraacetic acid polyethylene glycol, and the outer core is gold particles containing a sulfydryl structure and modified by 1, 2-bis (2-aminophenoxy) ethane-N, N, N ', N'-tetraacetic acid polyethylene glycol; and the shell is gel formed by in-situ free radical polymerization of acrylamide, 2-methacryloyloxyethyl phosphorylcholine, diacrylated matrix metalloproteinase responsive polypeptide and an initiator. The calcium ion nano-chelating agent is prepared by firstly preparing the calcium ion chelating agent polymer and then polymerizing on the surface of the inner core to form the gel shell, the preparation method is simple and mild, the raw materials are easy to obtain, the preparation method is suitable for large-scale production, the selectivity of the prepared calcium ion nano-chelating agent to Ca < 2 + > is 100 times higher than that of Mg < 2 + >, and the calcium ion nano-chelating agent is used for preparing anti-tumor drugs.

Description

technical field [0001] The invention belongs to the technical field of chelating agent materials, and relates to an ion nano-chelating agent, in particular to a calcium ion nano-chelating agent and its preparation method and application. Background technique [0002] Calcium ions are one of the most important second messengers in cells. During the development of tumors, abnormal calcium ion concentrations will activate the transduction pathways of circulating signals triggered by calcium ions to promote cell proliferation, tumorigenesis and migration, thus promoting tumorigenesis. Cells proliferate indefinitely. Therefore, effectively regulating the calcium ion concentration in tumor cells is an important strategy in the development of tumor drugs. [0003] In recent years, drugs that block active calcium signaling pathways in cells, including calcium channel blockers, have been developed for cancer treatment. However, adverse reactions such as edema, flushing, headache, d...

Claims

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Application Information

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Patent Type & AuthorityApplications(China)
IPC IPC(8): A61K9/51A61K47/42A61K47/32A61K47/60A61K31/198A61P35/00
CPCA61K9/5169A61K9/5138A61K47/60A61K31/198A61P35/00
Inventor王育才蒋为董旺汪沁
OwnerUNIV OF SCI & TECH OF CHINA