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Antibody coupling type active targeting drug-loading long-circulating lipidosome and preparation method thereof

A long-circulation liposome and active targeting technology, which is applied in liposome delivery, antineoplastic drugs, pharmaceutical formulations, etc., can solve problems that have not yet been reported on oxaliplatin liposome research

Inactive Publication Date: 2018-05-08
SOUTHEAST UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, the research on oxaliplatin liposomes is relatively extensive, but there is no relevant research report on anti-vascular endothelial growth factor monoclonal antibody conjugated oxaliplatin liposomes

Method used

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  • Antibody coupling type active targeting drug-loading long-circulating lipidosome and preparation method thereof

Examples

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Effect test

example 1

[0026] Example 1, accurately weigh an appropriate amount of phospholipids, cholesterol, distearoylphosphatidylethanolamine-polyethylene glycol 2000, phospholipids-polyethylene glycol 2000-maleimide (mass ratio is 4:1:1:0.4) Dissolve in chloroform, then weigh an appropriate amount of oxaliplatin raw material and dissolve in 5% glucose solution. Under the ultrasound of the probe, the solution dissolved in oxaliplatin was slowly added dropwise to chloroform to form a uniform and stable W / O emulsion, and the volume of aqueous phase: organic phase was 1:3. Then the chloroform was removed by rotary evaporation under reduced pressure at 45° C. to obtain a liposome solution, and then the liposome solution was freeze-thawed 3 times, and passed through a 0.2 μm carbonate membrane 8 times to obtain oxaliplatin-loaded long-circulation liposomes. The monoclonal antibody and 2-iminosulfane hydrochloride were mixed in an EP tube at a molar ratio of 1:200, placed on a low-speed shaker at room...

example 2

[0027] Example 2, accurately weigh an appropriate amount of phospholipids, cholesterol, distearoylphosphatidylethanolamine-polyethylene glycol 2000, phospholipids-polyethylene glycol 2000-maleimide (mass ratio is 4:1:0.6:0.4 ) was dissolved in chloroform, and then an appropriate amount of oxaliplatin bulk drug was weighed and dissolved in 5% glucose solution. Under the ultrasound of the probe, the solution dissolved in oxaliplatin was slowly added dropwise to chloroform to form a uniform and stable W / O emulsion, and the volume of aqueous phase: organic phase was 1:3. Then the chloroform was removed by rotary evaporation under reduced pressure at 45°C to obtain a liposome solution, then the liposome solution was freeze-thawed 3 times, and passed through a 0.2 μm carbonate membrane 6 times to obtain the oxaliplatin-loaded long-circulation liposome. The monoclonal antibody and 2-iminosulfane hydrochloride were mixed in an EP tube at a molar ratio of 1:100, placed on a low-speed s...

example 3

[0028] Example 3, accurately weigh an appropriate amount of phospholipids, cholesterol, distearoylphosphatidylethanolamine-polyethylene glycol 2000, phospholipids-polyethylene glycol 2000-maleimide and be dissolved in chloroform (mass ratio is 5:1: 0.8:0.4), then weigh an appropriate amount of oxaliplatin bulk drug and dissolve it in 5% glucose solution. Under the ultrasound of the probe, the solution dissolved in oxaliplatin was slowly added dropwise to chloroform to form a uniform and stable W / O emulsion, and the volume of aqueous phase: organic phase was 1:3. Then the chloroform was removed by rotary evaporation under reduced pressure at 45° C. to obtain a liposome solution, and then the liposome solution was freeze-thawed 3 times, and passed through a 0.2 μm carbonate membrane 8 times to obtain oxaliplatin-loaded long-circulation liposomes. The monoclonal antibody and 2-iminosulfane hydrochloride were mixed in an EP tube at a molar ratio of 1:200, placed on a low-speed sha...

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Abstract

The invention discloses an antibody coupling type active targeting drug-loading long-circulating lipidosome and a preparation method thereof. The targeting long-circulating lipidosome comprises an antibody, a chemotherapeutic drug and a lipidosome body, wherein the antibody is anti-angiogenic endothelia growth factor monoclonal antibody; the chemotherapeutic drug is oxaliplatin; the long-circulating lipidosome body comprises phospholipid, cholesterol and distearoyl phosphoethanolamine-polyethylene glycol 2000; the antibody is coupled with oxaliplatin lipidosome and prepared through the raw materials including phospholipid, cholesterol, distearoyl phosphoethanolamine-polyethylene glycol 2000, novel anti-angiogenic endothelia growth factor monoclonal antibody (anti-VEGF monoclonal antibody)and antitumor drug that is oxaliplatin. The primary result is obtained at present and shows that the antibody coupling rate is 43.76%; the activity remaining rate of the antibody is 84.16%. Therefore,the active targeting lipidosome can be effectively and specifically combined with vascular endothelial growth factor, as a result, the toxicity reducing and efficacy enhancing effects can be achieved.

Description

technical field [0001] The invention relates to an active targeted drug-loaded long-circulation liposome technology, which belongs to the technical field of medicine preparation. Background technique [0002] At present, hepatocellular carcinoma is a malignant tumor with high incidence and common occurrence in my country, and its morbidity and mortality rank first in the world. Although there are a variety of treatment methods, including surgery, local ablation, hepatic artery intervention, chemotherapy and radiotherapy, etc., only 15% of them can be operated on, and most of the hepatocellular carcinomas have reached the middle and late stages when they are diagnosed clinically. Ablation, hepatic artery intervention, and drug therapy became the main palliative treatments, but their effect on improving survival was limited. Therefore, there is an urgent need to find new breakthrough treatments. [0003] Tumor growth is closely related to angiogenesis. Selecting important fa...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/24A61K31/555A61K47/68A61P35/00
CPCA61K9/127A61K31/555A61K47/24
Inventor 刘琳吕洋洋顾宁田吉来
Owner SOUTHEAST UNIV
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