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T7 peptide -modified ZL006 long-circulating liposome and preparation method thereof

A long-circulating liposome and phospholipid technology, applied in the field of medicine, can solve the problems such as the limited ability of ZL006 to pass through the blood-brain barrier, the reduction of drug efficacy, etc., and achieve the advantages of reducing systemic side effects, simple and easy preparation method, and good stability. Effect

Inactive Publication Date: 2014-06-18
NANJING MEDICAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the present invention is to provide a T7 peptide-modified ZL006 long-circulating liposome, which solves the defects in the prior art that ZL006 has limited ability to penetrate the blood-brain barrier and greatly reduces the curative effect of the drug.

Method used

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  • T7 peptide -modified ZL006 long-circulating liposome and preparation method thereof
  • T7 peptide -modified ZL006 long-circulating liposome and preparation method thereof
  • T7 peptide -modified ZL006 long-circulating liposome and preparation method thereof

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preparation example Construction

[0032] The preparation method of the ZL006 long-circulation liposome modified by the above-mentioned T7 peptide comprises the following steps:

[0033] Step 1, dissolve maleimide-polyethylene glycol-phosphatidylethanolamine in N,N-dimethylformamide to obtain maleimide-polyethylene glycol-phosphatidylethanolamine solution, and dissolve T7 peptide The T7 peptide solution was obtained in a phosphate buffer solution with pH=6.5-7.5; the maleimide-polyethylene glycol-phosphatidylethanolamine solution and the T7 peptide solution were respectively added dropwise to the phosphate buffer solution with a pH=6.5-7.5 In the liquid, protected by nitrogen gas, stirred for 10-14 hours to obtain a reaction liquid, wherein the molar ratio of T7 peptide to maleimide-polyethylene glycol-phosphatidylethanolamine is 1:1-5:1;

[0034] Step 2. Evaporate the reaction solution obtained in step 1 to remove N,N-dimethylformamide, then dialyze to remove unreacted T7 peptide and maleimide-polyethylene gly...

Embodiment 1

[0037] Synthesis, Purification and Characterization of T7 Peptide-Polyethylene Glycol 2000-Distearoyl Phosphatidylethanolamine (HAIYPRH-PEG2000-DSPE)

[0038] Take 8mg of maleimide-polyethylene glycol 2000-distearoylphosphatidylethanolamine (Mal-PEG2000-DSPE), dissolve it in 1ml N,N-dimethylformamide (DMF); take another 10mg of T7 peptide, Dissolve in 1ml pH7.0 phosphate buffer. The two solutions were added dropwise to 10 ml of pH 7.0 phosphate buffer, under nitrogen protection, and magnetically stirred overnight to obtain the primary product. The initial product was removed by a 30°C rotary evaporator to remove DMF while concentrating the volume to obtain the product. The product was then dialyzed (molecular weight cut-off 3.5 KDa) to remove excess T7 peptide. After lyophilization, the final product of HAIYPRH-PEG2000-DSPE was obtained. The structure was characterized by NMR, see figure 1 , where A is the NMR spectrum of Mal-PEG2000-DSPE, B is the NMR spectrum of HAIYPRH-...

Embodiment 2

[0040] Preparation and characterization of T7 peptide-modified ZL006 long-circulating liposomes (HAIYPRH-long-circulating liposome-ZL006)

[0041] Prepared by ethanol injection method, dissolve soybean lecithin, cholesterol, methoxy-polyethylene glycol 2000-distearoylphosphatidylethanolamine (mPEG2000-DSPE), HAIYPRH-PEG2000-DSPE and ZL006 in 7.5ml ethanol, fully Vortex mixing, wherein the quality of soybean lecithin is 80 mg, the molar ratio of soybean lecithin / cholesterol / mPEG2000-DSPE / HAIYPRH-PEG2000-DSPE is 20:5:2:1, and the mass ratio of soybean lecithin / ZL006 is 20:5 . Then, the uniformly mixed solution was slowly dropped into 25 ml of pH5.5 phosphate buffer solution at 50° C. and a rotating speed of 350 rpm. After the dropwise addition was completed, keep at 50°C and continue to stir for 15 minutes. Subsequently, evaporate in a rotary evaporator for 5 min in a water bath at 60 °C (without degassing). After rotary evaporation, use an ultrasonic cell pulverizer to reduc...

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Abstract

The invention discloses a T7 peptide-modified ZL006 long-circulating liposome which comprises phospholipid, cholesterol, methoxy-polyethylene glycol-phosphatidyl ethanolamine, T7 peptide-polyethylene glycol-phosphatidyl ethanolamine and therapeutically effective amount of ZL006. The invention also discloses a preparation method of the T7-modified ZL006 long-circulating liposome. According to the T7-modified ZL006 long-circulating liposome, the medicine ZL006 is encapsulated in a lipid bilayer, so that the circulating time of the medicine in the body is greatly prolonged; by means of T7 peptide modification, the blood brain barrier penetration capability of the medicine is improved, the medicine for treating cerebral apoplexy is effectively and concentratedly transferred to the cerebral apoplexy part, the treatment effect of the medicine is furthest exerted, and meanwhile, the toxic and side effects of the whole body are reduced.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a T7 peptide-modified ZL006 long-circulation liposome and a preparation method thereof. Background technique [0002] With the aging trend of human society and the deterioration of the global ecological environment, the incidence of brain diseases is increasing year by year, becoming a major disease that endangers human life and health. Among them, stroke is a neurological disease with high death rate, high disability rate and high recurrence rate, and is listed as the third largest killer of human beings after cardiovascular diseases and malignant tumors. Clinically, more than 80% of strokes are ischemic strokes, so research on drug therapy for ischemic strokes has great clinical significance. Studies have shown that under ischemic conditions, the excessive release of excitatory amino acids (such as glutamate) in brain tissue causes excessive activation of N-methyl-D-aspartate...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/42A61K31/606A61P9/10A61P25/00
Inventor 徐群为辛洪亮王中元赵越吴琳王宝彦吕玲燕
Owner NANJING MEDICAL UNIV
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