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A kind of anti-tumor polypeptide nano drug and its preparation method and application

A nano-drug and anti-tumor technology, applied in the direction of anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve problems such as insufficient stability and molecular structure damage, and achieve the effects of improving bioavailability, prolonging half-life, and good therapeutic effect

Active Publication Date: 2017-12-12
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Peptide itself has good biocompatibility and controllable degradation performance, but its stability in vivo is not enough, and its molecular structure is easily destroyed

Method used

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  • A kind of anti-tumor polypeptide nano drug and its preparation method and application
  • A kind of anti-tumor polypeptide nano drug and its preparation method and application
  • A kind of anti-tumor polypeptide nano drug and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0073] In this example, the anti-tumor polypeptide nano drug was prepared by the following method, which is:

[0074] M. Lourdes Ponce et al., Cancer Research, 2003, 63: 5060-5064 provide the C16Y polypeptide that inhibits tumor angiogenesis and tumor growth (the sequence starting from the amino terminal is: aspartic acid-phenylalanine-lysine amino acid-leucine-phenylalanine-alanine-valine-tyrosine-isoleucine-lysine-tyrosine-arginine) as a hydrophilic anti-tumor polypeptide, according to Literature (Lihong Liu et al., Nature Nanotechnology, 2009, 4:457-463 and Ying Zhao et al., J Control Release, 2014, 177:11-19) provide solid-phase synthesis and peptide purification methods, the eight leucine The hydrophobic polypeptide composed of 2 glycines is connected to the anti-tumor polypeptide C16Y, and the tripeptide formed by 3 lysines is connected at the amino terminal of the hydrophobic polypeptide, and then the amino group on the lysine (including the terminal amino group and si...

Embodiment 2

[0087] In this example, through the same synthesis method and steps as in Example 1, 3 isoleucine, 2 methionine and 1 lysine were coupled to the anti-tumor polypeptide C16Y, and the lysine DEAP molecules are connected to the terminal amino group and the side chain amino group, and the amphipathic anti-tumor polypeptide coupled with DEAP is obtained. The anti-tumor polypeptide nano drug system was obtained through the same self-assembly process as in Example 1.

[0088] The structure of the amphiphilic anti-tumor polypeptide coupled with DEAP obtained in this example is confirmed by means of high performance liquid chromatography and mass spectrometry: C16Y-(tripeptide formed by isoleucine)-(dipeptide formed by methionine) )-lysine-(DEAP) 2 .

[0089] The morphology and particle size of the obtained anti-tumor polypeptide nano-drug system were characterized by transmission electron microscope and laser particle size analyzer. It is 40-200nm, the average particle size is abou...

Embodiment 3

[0091] In this example, through the same synthesis method and steps as in Example 1, 20 alanines and 5 lysines were coupled to the anti-tumor polypeptide C16Y, and the terminal amino group and side of lysine A DEAP molecule is connected to the chain amino group, and an amphipathic anti-tumor polypeptide coupled with DEAP is obtained. The anti-tumor polypeptide nano drug system was obtained through the same self-assembly process as in Example 1.

[0092] The structure of the amphiphilic anti-tumor polypeptide coupled with DEAP obtained in this example was confirmed by means of high performance liquid chromatography and mass spectrometry: C16Y-(polypeptide formed by 20 alanines)-(5 lysines Polypeptides formed)-(DEAP) 6 .

[0093] The morphology and particle size of the obtained anti-tumor polypeptide nano-drug system were characterized by transmission electron microscope and laser particle size analyzer. It is 30-160nm, the average particle size is about 100.5nm, and the disp...

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Abstract

The invention provides an antineoplastic polypeptide nanometer drug, and a preparation method and application thereof. The antineoplastic polypeptide nanometer drug comprises amphipathic antineoplastic polypeptides and acid responsiveness functional molecules link-coupled with the amphipathic antineoplastic polypeptides. Amino acid is taken as the raw material to synthesize amphipathic polypeptide molecules, and then acid responsiveness functional molecules are introduced into the amphipathic antineoplastic polypeptide molecules to be subjected to self-assembling to form the antineoplastic polypeptide nanometer drug. The antineoplastic polypeptide nanometer drug provided by the invention has good biocompatibility, smaller toxic and side effects, acid responsiveness, high bioavailability and high biosecurity. The preparation method provided by the invention is simple, covalent bonds are not produced in the self-assembling process, reverse reaction is avoided, and the prepared antineoplastic polypeptide nanometer drug has a broad application prospect.

Description

technical field [0001] The invention relates to the field of nano-medicine, and relates to an anti-tumor polypeptide nano-medicine and a preparation method and application thereof. Background technique [0002] In recent years, the research and development of anti-tumor peptide drugs has attracted much attention. Compared with antibodies and small-molecule drugs, peptide drugs have low immunogenicity, high receptor binding rate, low preparation cost, and are easy to modify and combined application. Organ metabolism. Therefore, improving the pharmacokinetics of polypeptides without reducing their efficacy is an important direction for the development of polypeptide drugs. [0003] Nano-drugs are emerging drug dosage forms. By designing and regulating the nano-characteristics of organic or inorganic materials, nano-carriers with stable structures, diverse functions and good biocompatibility can be prepared, which can significantly prolong the half-life of drugs, improve targ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/54A61K9/14A61K38/00A61K38/10A61K38/08A61P35/00
Inventor 丁艳萍聂广军季天骄赵颖
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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