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Method of manufacturing pharmaceutical preparations containing liposomes

A technology of a liposome preparation and a manufacturing method, which is applied in the field of manufacture of liposome-containing preparations and can solve problems such as stability problems

Inactive Publication Date: 2007-07-18
KONICA MINOLTA MEDICAL & GRAPHICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, even liposomes obtained by this method still have the problem of stability in vivo

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0109] 300 mg of dipalmitoylphosphatidylcholine (DPPC, manufactured by NOF Corporation) and 100 mg of PEG-phospholipid (SUNBRIGHT DSPE-020CN, manufactured by NOF Corporation) were placed in a pressure vessel made of stainless steel, and then 13 g of liquid carbon dioxide was injected After that, adjust the inside of the container to 50°C, 120kg / cm 2 , adjust carbon dioxide to a supercritical state, maintain its state, and mix 10 g of iohexol solution (iodine content rate 240 mg / mL), using an electromagnetic stirrer (stirring bar: roughly cylindrical shape with a length of 15 mm and a diameter of 5 mm), Stir vigorously at 1000 rpm for 10 minutes. Then, depressurize the pressure vessel to reduce the pressure to about 10kg / cm 2 , to emit carbon dioxide. Utilizing the pressure in the container, the dispersion liquid is discharged and recovered from the container to obtain a liposome dispersion liquid containing iohexol. Further, the obtained dispersion liquid was subjected to p...

Embodiment 2

[0112] 900 mg of dipalmitoylphosphatidylcholine (DPPC, manufactured by NOF Co., Ltd.) was placed in a pressure vessel made of stainless steel, and then, after injecting 40 g of liquid carbon dioxide, the inside of the vessel was adjusted to 40°C and 120 kg / cm 2 , adjust carbon dioxide to a supercritical state, maintain its state, and mix 40g of iopamidol solution (iodine content rate is 200mg / mL), using a Sany motor (three -one motor), stirring vigorously for 20 minutes at a rotation speed of 2000rpm. Then, depressurize the pressure vessel to reduce the pressure to about 10kg / cm 2 , to emit carbon dioxide. Utilizing the pressure in the container, the dispersion liquid is discharged and recovered from the container to obtain a liposome dispersion liquid containing iopamidol. Further, the obtained dispersion liquid was subjected to pressure filtration with a 0.45 μm cellulose filter. After filtration, the liposome dispersion was filled into a glass ampoule and subjected to au...

Embodiment 3

[0115] 300 mg of dimyristoylphosphatidylcholine (DMPC, manufactured by NOF Co., Ltd.), 40 mg of cholesterol HP (manufactured by NOF Corporation), and 50 mg of dipalmitoyl as a diol phospholipid were placed in a pressure vessel made of stainless steel. Phosphatidylcholine (COATSOMEMG-6060LS, manufactured by NOF Corporation), and then, after injecting 13g of liquid carbon dioxide, the inside of the container was adjusted to 48°C and 120kg / cm 2 , adjust carbon dioxide to a supercritical state, maintain its state, and mix 10 g of iohexol solution (iodine content rate: 200 mg / mL), using an electromagnetic stirrer (stirring bar: roughly cylindrical shape with a length of 15 mm and a diameter of 5 mm), Stir vigorously at 1200 rpm for 3 minutes. Then, depressurize the pressure vessel to reduce the pressure to about 10kg / cm 2 , to emit carbon dioxide. Utilizing the pressure in the container, the dispersion liquid is discharged and recovered from the container to obtain a liposome dis...

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Abstract

It is intended to provide a method of producing a liposome-containing preparation which is excellent in the stability in vivo and contains liposomes having a drug entrapped therein at an elevated ratio, and a liposome-containing preparation obtained by this method. The method of producing a liposome-containing preparation as described above is characterized by comprising mixing carbon dioxide in the supercritical or subcritical state, a liposome membrane-constituting substance at least containing a phospholipid having a transition temperature and a water-soluble drug in a pressure container and discharging the carbon dioxide by depressurizing the inside of the container to thereby prepare an aqueous dispersion of liposomes having the water-soluble drug entrapped therein.

Description

technical field [0001] The present invention relates to a method for producing a liposome-containing preparation, and to a liposome-containing preparation obtained by the method, which has excellent stability in vivo and contains liposomes with a high drug encapsulation efficiency. Background technique [0002] Liposomes are closed vesicles of bimolecular membranes (liposome membranes) mainly composed of phospholipids. Since they have similar structures and functions to biological membranes, they have been used as various preparation materials in the past. Since liposomes can construct a so-called capsule structure that holds water-soluble drugs in the water phase inside and oil-soluble drugs inside the bimolecular membrane, it can be used in various fields such as diagnosis, treatment, and cosmetics. In addition, in recent years, its application in drug delivery systems (DDS) has been extensively studied. [0003] In order to prepare such drug-encapsulating liposomes, the ...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K45/00A61K47/34A61P35/00A61K49/04A61K47/10
Inventor 长池千秋元杭康之
Owner KONICA MINOLTA MEDICAL & GRAPHICS INC
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