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Preparation and application of human serum albumin-ruthenium inorganic drug complex

A human serum albumin, inorganic drug technology, applied in the field of antitumor drugs, can solve problems such as toxic and side effects, achieve the effects of reducing toxicity, high vascular permeability and retention rate, and improving targeting

Inactive Publication Date: 2015-11-18
GUANGXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, we have to face a reality: anti-tumor inorganic drugs are still a double-edged sword. While treating diseases, they will inevitably produce many side effects. Although NAMI-A has completed the first clinical phase, it is still very toxic. side effect

Method used

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  • Preparation and application of human serum albumin-ruthenium inorganic drug complex
  • Preparation and application of human serum albumin-ruthenium inorganic drug complex
  • Preparation and application of human serum albumin-ruthenium inorganic drug complex

Examples

Experimental program
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Effect test

Embodiment 1

[0020] Embodiment 1: the preparation of human serum albumin-NAMI-A ruthenium inorganic drug complex

[0021] NAMI-A was prepared according to literature: 1g RuCl 3 Add to 30ml of ethanol, reflux for 3 hours to obtain a dark green solution, filter, concentrate to one-tenth of the initial volume, then add 1ml of concentrated hydrochloric acid and 2ml of DMSO, keep at 80°C for 15 minutes to obtain a bright orange solution. Cool the solution to room temperature, add 10ml of acetone to obtain orange-red crystals, add a few drops of diethyl ether to accelerate its crystallization, and collect by filtration. Wash with 20ml of cold acetone, then wash with 10ml of diethyl ether, and dry in vacuo to obtain 1.5g with a yield of 72%. Suspend 1.0 g of the above product in 20 ml of acetone, add 0.49 g of imidazole, stir for 4 hours, the color changes from orange to brick red, wash with 10 ml of acetone and 10 ml of ether, and dry the product at 60°C.

[0022] Weigh the prepared NAMI-A dr...

Embodiment 2

[0023] Embodiment 2: The structure determination of human serum albumin-NAMI-A ruthenium inorganic drug complex

[0024] Mix HSA (1.5mM, 100μL), saturated hexadecanoic acid (2.5mM, 960μL), and drugs (100mM, 1.5μL), incubate for 24 hours, centrifuge to remove the precipitate, then concentrate, wash repeatedly with deionized water twice, and finally Concentrate to 100 μL and incubate albumin suitable for X-ray diffraction by gas phase diffusion method (26-30% PEG3350, 5% glycerol, 5% 2-methyl-1,3-propanediol) in a sitting drop plate - Fatty acid-metal drug complex crystals. Crystal data were collected using the Shanghai Synchrotron Radiation Facility. After processing the data with HKL2000, use the molrep program of ccp4 to use the protein with strong homology to the amino acid sequence of the protein in the protein database as a template, quickly rotate and translate the function to find a suitable template, and integrate it. If there is no protein with strong homology in the...

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Abstract

The invention discloses preparation and application of a human serum albumin-NAMI-A ruthenium inorganic medicine compound. NAMI-A and the human serum albumin are incubated, the mixture is concentrated, the concentrated mixture is repeatedly washed by secondary deionized water till the DMSO content is smaller than 0.01 percent, then concentration is performed to obtain the human serum albumin-NAMI-A ruthenium inorganic medicine compound, and the compound is prepared into an injection, tablets, pills, capsules, a suspending agent or an emulsion to treat breast cancer, stomach cancer, lung cancer, colon cancer or liver cancer. The compound has high vascular permeability and retention rate, the medicine selectivity gathers in tumor cells while not influencing normal cells, the targeting of the ruthenium inorganic medicine is remarkably improved and the toxicity is greatly lowered.

Description

technical field [0001] The invention relates to anti-tumor drugs, in particular to the preparation of human serum albumin-NAMI-A ruthenium inorganic drug complex and its application in anti-tumor diseases. Background technique [0002] In recent years, ruthenium complexes have been extensively studied as new anticancer drugs. Due to the unique physical and chemical properties of ruthenium complexes, it is generally believed internationally that ruthenium complexes are low-toxic, easy to absorb and excreted quickly in the body. At present, hundreds of ruthenium complexes have been synthesized, and NAMI-A has completed Phase I clinical trials and is entering Phase II clinical trials. However, we have to face a reality: anti-tumor inorganic drugs are still a double-edged sword. While treating diseases, they will inevitably produce many side effects. Although NAMI-A has completed the first clinical phase, it is still very toxic. side effect. Obviously, how to improve the inte...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/48A61K31/555A61P35/00A61K47/64
Inventor 杨峰张耀梁宏李梅
Owner GUANGXI NORMAL UNIV
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