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A drug-loaded fat emulsion co-loaded with oxaliplatin and irinotecan and its preparation method

A technology of irinotecan and oxaliplatin, which is applied in the field of oxaliplatin and irinotecan co-loaded drug-loaded fat emulsion and its preparation, which can solve the problems of co-loaded fat emulsion and improve the anti-tumor effect , outstanding synergistic effect, and good physical stability

Active Publication Date: 2020-02-18
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no report of co-loaded lipid emulsion with oxaliplatin and irinotecan as therapeutic drugs

Method used

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  • A drug-loaded fat emulsion co-loaded with oxaliplatin and irinotecan and its preparation method
  • A drug-loaded fat emulsion co-loaded with oxaliplatin and irinotecan and its preparation method
  • A drug-loaded fat emulsion co-loaded with oxaliplatin and irinotecan and its preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1: Oxaliplatin and irinotecan were used to prepare drug lipid complexes respectively.

[0042] A fat emulsion co-carried with oxaliplatin and irinotecan, 20 mg of oxaliplatin and 300 mg of egg yolk phospholipids are dissolved in 20 ml of methanol / dichloromethane (volume ratio 9:1), 50 mg of irinotecan and 200 mg of egg yolk phospholipids are dissolved After reacting in 5ml of dichloromethane for a certain period of time, the two were vacuumized respectively to obtain oxaliplatin-lipid complex and irinotecan-lipid complex; the two drug-lipid complexes were redissolved in 4ml of dichloromethane , add MCT 2g, oleic acid 50mg, obtain oil phase after vacuumizing. 200 mg of Pluronic F68 and 800 mg of glycerin were dissolved in water to obtain an aqueous phase. After the oil phase and the water phase were preheated at 60°C respectively, they were mixed at a shear rate of 6000r / min to obtain colostrum, and water was added to make the final volume 40ml; followed by 15 c...

Embodiment 2

[0044] Example 2: Oxaliplatin and irinotecan were used to simultaneously prepare drug lipid complexes.

[0045] A kind of oxaliplatin and irinotecan co-carrying fat emulsion, take oxaliplatin 20mg, irinotecan 50mg and soybean lecithin 500mg and dissolve in methanol / methylene chloride 20ml (volume ratio 9:1), after reacting for a certain period of time , vacuumize to obtain oxaliplatin / irinotecan-lipid complex; redissolve the drug-lipid complex with 4ml of dichloromethane, add MCT 4g, oleic acid 50mg, and obtain an oil phase after vacuuming. 200 mg of Pluronic F68 and 900 mg of glycerin were dissolved in water to obtain an aqueous phase. After the oil phase and the water phase were preheated at 60°C respectively, they were mixed at a shear rate of 8000r / min to obtain colostrum, and water was added to make the final volume 40ml; followed by 15 cycles of high-pressure emulsification at 10Mpa to obtain co-loaded fat milk.

[0046] The concentrations of oxaliplatin and irinotecan...

Embodiment 3

[0047] Example 3: Oxaliplatin preparation of drug-lipoplexes and irinotecan were directly loaded.

[0048] A fat emulsion co-loaded with oxaliplatin and irinotecan. Take 20 mg of oxaliplatin and 300 mg of hydrogenated soybean lecithin and dissolve them in 20 ml of methanol / chloroform (volume ratio 9:1). After reacting for a certain period of time, vacuumize to obtain oxaliplatin Liplatin-lipid complex. The drug-lipid complex was redissolved with 4ml of chloroform, and 50mg of irinotecan, 2g of MCT, and 50mg of cholic acid were added, and an oily phase was obtained after vacuuming. 300 mg of Pluronic F68 and 800 mg of glycerin were dissolved in water to obtain an aqueous phase. After the oil phase and the water phase were preheated at 50°C, they were mixed at a shear rate of 10,000r / min to obtain colostrum, and water was added to make the final volume 40ml; then the high-pressure emulsion was circulated 10 times at 10Mpa to obtain co-loaded fat milk.

[0049] The concentrati...

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Abstract

The invention discloses an oxaliplatin-and-irinotecan jointly loading lipid emulsion prepared based on the drug lipid composite technology. The oxaliplatin-and-irinotecan jointly loading lipid emulsion is prepared from oxaliplatin with the concentration of 0.5 mg / ml-2 mg / ml, irinotecan with the concentration of 0.5 mg / ml-5 mg / ml, 5%-20% of injection oil, 0.5%-2.5% of phospholipid, 0.1%-2% of pluronic F68, 0.01%-0.5% of a stabilizing agent, 0.1%-2.5% of glycerol and water. By means of the jointly-loading lipid emulsion prepared with the drug lipid composite technology, synchronous releasing of two drugs in the human body can be coordinated, it is guaranteed that the two drugs are kept in the optimized dosage ratio when reaching the tumor site, and therefore the best collaborative effect is achieved.

Description

technical field [0001] The invention relates to the technical field of fat emulsion preparations, in particular to a drug-loaded fat emulsion co-loaded with oxaliplatin and irinotecan and a preparation method thereof. Background technique [0002] The incidence of colorectal cancer ranks third among various tumor diseases, and traditional chemotherapy drugs are still an indispensable means in the current clinical treatment of colorectal cancer. Due to the heterogeneity and genetic complexity of cancer, single chemotherapy drugs often have limited therapeutic effects and are prone to multidrug resistance, so combination therapy or multiple treatments are often required. Among them, the combination of oxaliplatin and irinotecan is recommended in the "Guidelines for the Clinical Treatment of Colon Cancer" published by the NCCN (National Comprehensive Cancer Network) in the United States for the treatment of progressive tumors after the first chemotherapy failure. of metastatic...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/107A61K47/14A61K47/06A61K47/24A61K47/12A61K31/555A61K31/4745A61P35/00
CPCA61K9/107A61K31/4745A61K31/555A61K47/06A61K47/12A61K47/14A61K47/24A61K2300/00
Inventor 张娜张波杨绍梅王天琪刘永军张璟
Owner SHANDONG UNIV
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