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Elastic targeting polypeptide-based medicine-carrying nanoparticle as well as preparation method and application thereof

A technology targeting peptides and drug-loaded nanometers, which is applied in the field of medicine, can solve the problems of large side effects and poor targeting selectivity of anticancer drugs, and achieve the effects of high drug loading rate, expansion and efficacy, and small dispersion

Pending Publication Date: 2020-06-30
THE FIRST AFFILIATED HOSPITAL OF HAINAN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Therefore, it is necessary to prepare a drug-loaded nanoparticle based on an elastic targeting polypeptide to solve the problems of poor targeting selectivity or large side effects of existing anticancer drugs

Method used

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  • Elastic targeting polypeptide-based medicine-carrying nanoparticle as well as preparation method and application thereof
  • Elastic targeting polypeptide-based medicine-carrying nanoparticle as well as preparation method and application thereof
  • Elastic targeting polypeptide-based medicine-carrying nanoparticle as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Example 1: Preparation of Elastic Targeting Polypeptide ABD-iTEP70-(GGGGC)8

[0019] First design the amino acid sequence ABD and iTEP, and then use the existing peptide synthesis method to prepare

[0020] ABD-(iTEP)70-(GGGGC)8, where

[0021] ABD amino acid sequence: LAEAKVLANRELDKYGVSDFYKRLINKAKTVEGVEALKLHILAALP

[0022] Amino acid sequence of iTEP: GAGVPG

[0023] After the gene encoding the elastic targeting polypeptide ABD-(iTEP)70-(GGGGC)8 was synthesized, it was digested and inserted into the modified pET25b(+) vector to construct a recombinant expression plasmid; the gene sequence was successfully prepared after sequencing.

Embodiment 2

[0024] Example 2: Preparation of Elastic Targeting Polypeptide ABD-(iTEP)70-(GGGGGGC)8

[0025] First design the amino acid sequences ABD and iTEP, and then prepare ABD-(iTEP)70-(GGGGGGC)8 using the existing peptide synthesis method, wherein

[0026] ABD amino acid sequence: LAEAKVLANRELDKYGVSDFYKRLINKAKTVEGVEALKLHILAALP

[0027] Amino acid sequence of iTEP: GAGVPG

[0028] After the gene encoding the elastic targeting polypeptide ABD-(iTEP)70-(GGGGGGC)8 was synthesized, it was digested and inserted into the modified pET25b(+) vector to construct a recombinant expression plasmid; its gene sequence was successfully prepared after sequencing.

Embodiment 3

[0029] Example three: Synthesis of modified paclitaxel PTX-LEV-MECH

[0030]

[0031] Synthesis of Compound 1: Dissolve hydrazine hydrate (20.0 g, 0.40 mmol) in 80 mL of isopropanol at 0° C., then add di-tert-butyl dicarbonate (43.6 g, 0.20 mmol) to the solution, and dissolve the reaction solution The temperature was raised to room temperature, stirred for 1 hour, the solvent was removed, the residue was dissolved in dichloromethane, the insoluble matter was removed by filtration, and the organic phase was concentrated to obtain compound 1 (19.4 g, 74% yield) as a white solid. 1 H NMR (400MHz, CDCl 3 )δ1.46(s, 9H)

[0032] Synthesis of Compound 2: Maleic anhydride (5.00 g, 51.0 mmol) was dissolved in 100 mL of acetic acid at 0° C., and then 6-aminocaproic acid (6.69 g, 51.0 mmol) was slowly added to the above solution. The reaction solution was warmed up to room temperature and stirred for 4 hours. Subsequently, the reaction solution was heated to reflux overnight. Unde...

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Abstract

The invention discloses an elastic targeting polypeptide-based medicine-carrying nanoparticle. The nanoparticle is prepared from an elastic targeting polypeptide and a modified medicine, wherein the modified medicine is a modified paclitaxel PTX-LEV-MECH or modified salinomycin Sail-ABA-MPBH. The elastic targeting polypeptide-based medicine-carrying nanoparticle provided by the invention is 100nmor below in particle size, so that the dispersion degree is low, the medicine carrying rate is high, and the nanoparticle can be combined with in-vivo albumin for transferring and carrying medicine, and also can be combined with acidic rich cysteine specifically secreted by tumor cells, the drug is concentrated in the acidic environment, the breast cancer in-situ cancer is targeted for killing, and the toxic and side effects of the drug on the whole body are reduced; and the efficacy of treating breast cancer is increased and improved by utilizing the synergistic effect of two nanoparticles, the occurrence of the metastasis of the breast cancer cells through a lymphatic system and a blood system is reduced, and the occurrence of serious complications such as medical-source lymphatic edemacaused by a lymph node sweeping surgery is reduced.

Description

technical field [0001] The invention relates to the field of medical technology, in particular to a drug-loaded nanoparticle based on an elastic targeting polypeptide, a preparation method and application thereof. Background technique [0002] Tumor is one of the diseases that seriously endanger human health. The incidence and mortality of tumors in my country are increasing year by year. Among them, the top three in the incidence of malignant tumors are lung cancer, breast cancer and gastric cancer. Statistics show that in the past two years, the incidence of female cancer has increased significantly, especially breast cancer, which ranks first among female malignant tumors, with about 210,000 new cases each year. The incidence of cancer in my country is close to the world level, but the mortality rate is higher than the world level. The rising incidence of malignant tumors has become a public health problem and even a social problem that must be paid close attention to. ...

Claims

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Application Information

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IPC IPC(8): A61K47/64A61K47/69A61K31/337A61K31/351A61P35/00A61P35/04
CPCA61K47/64A61K47/6929A61K31/337A61K31/351A61P35/00A61P35/04
Inventor 许铁峰陈明南董书芸李丽李光磊张立明吕卓璇
Owner THE FIRST AFFILIATED HOSPITAL OF HAINAN MEDICAL UNIV
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