Novel method for preparing indissoluble medicaments liposome preparations

A technology of liposomes and blank liposomes, which is applied in liposome delivery, pharmaceutical formulations, drug combinations, etc., can solve the problems of unguaranteed stability of preparations, inconvenient clinical operations, adverse reactions, etc., and achieve good dilution stability , Avoid toxic and side effects, improve solubility

Active Publication Date: 2008-08-20
HAINAN SIMCERE PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But there is following shortcoming in this method: the one, use the organic solvent of 2.5%-10% (v / v), may destroy the stability of liposome; The solvent is easy to produce adverse reactions to the human body; the third is the blank liposome and drug lipid solution in the liquid state, the stability of the preparation cannot be guaranteed, especially for the small monolayer liposomes of about 50nm, aggregation and fusion are prone to occur , causing the particle size to become larger; the fourth is two bottles, which need to be mixed and loaded before use, which is inconvenient for clinical operation

Method used

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  • Novel method for preparing indissoluble medicaments liposome preparations
  • Novel method for preparing indissoluble medicaments liposome preparations
  • Novel method for preparing indissoluble medicaments liposome preparations

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Weigh 25g of soybean lecithin (SPC), 1.5g of DSPE-PEG2000, 2.4g of cholesterol and 0.1g of α-tocopherol and dissolve them in 20mL of 40-45°C absolute ethanol solution, and quickly add the dissolved lipid solution to a constant temperature (40- 45°C) of 10mM phosphate buffer 500mL (pH6.5), and continue to stir for 1h to form a liposome suspension, add 1g of docetaxel, stir at room temperature for 2h, and homogenize through a high-pressure homogenizer to 80±10nm. Use polysulfone vacuum fiber ultrafilter for membrane diafiltration, exchange 8 volumes of sucrose solution to remove residual ethanol, keep the temperature of the working stream at 20-30°C, use 10% sucrose-10mM phosphate solution to volume and adjust docetaxel The concentration is 2mg / mL, sterilized by filtration through a 0.22μm microporous membrane, and the finished product can be obtained by subpackaging. The finished product can be stored at 2°C-8°C or freeze-dried until use.

Embodiment 2

[0042] Weigh 30 g of egg yolk phospholipid (EPC), 1.5 g of egg yolk phosphatidylglycerol (EPG) and 0.12 g of α-tocopherol, add them to 500 mL of absolute ethanol, mix ultrasonically until dissolved, remove the organic solvent by spray drying, and use the obtained Place the lipid powder in a vacuum oven at 35°C overnight; prepare a 20mM sodium succinate solution, dissolve sucrose in the sodium succinate solution as a hydration solution, and adjust the pH value to 5.5 with an appropriate amount of succinic acid, water Multilamellar liposome suspension at a temperature of 40°C; add 1.5 g of micronized docetaxel, continue stirring for 2 h, homogenize with a high-pressure homogenizer until the average particle size is 120±10 nm, and set Contain and adjust the concentration of docetaxel to 3 mg / mL, filter and sterilize through a 0.22 μm microporous membrane, and then aliquot to obtain the finished product. The finished product can be stored at 2°C-8°C or freeze-dried until use.

Embodiment 2

[0043] Comparative example 2 common preparation method

[0044] Select egg yolk phospholipid (EPC) 30g, egg yolk phosphatidylglycerol (EPG) 1.5g and α-tocopherol 0.12g, be dissolved in chloroform-methanol (2: 1) solution and mix uniformly; The organic solvent is removed by vacuum evaporation method, Form lipid mixture; prepare 20mM sodium succinate solution, dissolve sucrose in sodium succinate solution as hydration solution, adjust pH to 5.5 with appropriate amount of succinic acid, hydration temperature is 40°C, mix multilamellar liposomes Suspension; after complete hydration, use a high-pressure homogenizer to homogenize to an average particle size of 120±10nm, dilute to volume with hydration solution and adjust to a docetaxel concentration of 3mg / mL, filter through a 0.22μm microporous membrane to remove The finished product can be stored at 2°C-8°C or freeze-dried until use.

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Abstract

The invention provides a new method for preparing an insoluble medicine lipidosome preparation, which is characterized in that the medicine can be carried on the dimolecular membrane via distributing and reducing grain diameter steps; and the preparation method is easy. The preparation method has the advantage of easily realizing the industrial production of the fat-soluble medicine lipidosome in virtue of the quite mature industrial production of the blank lipidsome at present.

Description

field of invention [0001] The present invention relates to a new method of preparing liposome formulations and liposome formulations produced by this method. Background technique [0002] How to increase the solubility of poorly soluble drugs is a hot spot in pharmaceutical research at present. Currently, clinically used injections of poorly soluble drugs are made by traditional methods, such as using compound solvents, solubilizers, etc., but this will increase the irritation or toxicity of the prescription. Clinical application can cause allergic reactions and even cause drug resistance. For example, the taxane drugs paclitaxel and docetaxel have good curative effects on various tumors, but because they are almost insoluble in water, the taxane preparations used in clinical practice are solubilized with Cremopher EL or Tween 80. After administration, some patients may experience allergic reactions such as drug-induced rash, shortness of breath, bronchospasm, hypotension, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K45/00A61K47/24A61K47/28A61K31/337A61P35/00
Inventor 林巧平王青松刘春晖许向阳
Owner HAINAN SIMCERE PHARMA CO LTD
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