Paclitaxel liposome and preparation method therefor

Abstract

The invention provides a Paclitaxel liposome and process for preparation, wherein the components include Paclitaxel 1-30%, phosphatides 1-95%, cholesterin 0-30%, thermo-sensible auxiliary material D 0-50%, auxiliary material G 0-50%, freeze-drying protecting agent 0-80%, octadecyl amine 0-10%, anti-oxidant 0.001-50% and right amount of buffer salt.

Description

technical field

[0001] The invention belongs to the technical field of medicine, and relates to thermosensitive liposomes, long-circulation liposomes and thermosensitive long-circulation liposome preparations of the antitumor drug paclitaxel, and also relates to preparation methods of these liposomes. Background technique

[0002] Paclitaxel is a monomeric compound with definite and strong anti-cancer effects discovered by humans in the late 20th century. Oncology has become the drug of choice.

[0003] At present, paclitaxel injection in clinical application includes domestic paclitaxel  , Taxol  , import Taxol  (USA BMS company), Anzatax  (Australian Fauliding company) and other products, these products all utilize surfactant solubilization method to solve the shortcoming that paclitaxel is insoluble in water, to reach the purpose of intravenous administration. However, these preparations have many side effects in clinical use, especially the existing commercially...

Examples

Embodiment 1

[0028] prescription:

[0029] Paclitaxel 0.4g

[0030] Soybean Lecithin for Injection 20.0g

[0031] Cholesterol 2.4g

[0032] Excipient D 5.0g

[0033] Octadecylamine 0.1g

[0034] Vitamin E 0.2g

[0035] Buffered saline solution to 200mL

[0036] Preparation Process:

[0037]Dissolve the prescribed amount of paclitaxel, soybean lecithin for injection, cholesterol, excipient D, and vitamin E in an organic solvent and pour it into a pear-shaped bottle, then add a small amount of buffered saline solution containing octadecylamine, ultrasonically make it into a uniform milk, and use a rotary evaporator The organic solvent was removed under reduced pressure to form a gel, vortexed and distilled under reduced pressure at intervals to obtain a white uniform liposome solution, and then the volume was adjusted to 200 mL with buffer solution. Then pass through the membrane (0.22 μm) under pressure to depyrogenize the entire particle, then pack into vials and freeze-dry to obtai...

Embodiment 2

[0039] prescription:

[0040] Paclitaxel 0.4g

[0041] Soybean Lecithin for Injection 20.0g

[0042] Cholesterol 2.4g

[0043] Excipient D 5.0g

[0044] Octadecylamine 0.1g

[0045] Vitamin E 0.2g

[0046] Buffered saline solution to 200mL

[0047] Preparation Process:

[0048] Dissolve the prescribed amount of paclitaxel, soybean lecithin for injection, cholesterol, excipient D, and vitamin E in an organic solvent and pour it into a pear-shaped bottle, then add a small amount of buffered saline solution containing octadecylamine, ultrasonically make it into a uniform milk, and use a rotary evaporator The organic solvent was removed under reduced pressure to form a gel, vortexed and distilled under reduced pressure at intervals to obtain a white uniform liposome solution, and then the volume was adjusted to 200 mL with buffer solution. Then pass through the membrane (0.22 μm) under pressure to depyrogenize the whole grain, pack into ampoules, freeze in the refrigerator ...

Embodiment 3

[0050] prescription:

[0051] Paclitaxel 0.4g

[0052] Soybean Lecithin for Injection 20.0g

[0053] Cholesterol 2.4g

[0054] Excipient D 5.0g

[0055] Sucrose 5.0g

[0056] Mannitol 0.1g

[0057] Octadecylamine 0.1g

[0058] Vitamin E 0.2g

[0059] Buffered saline solution to 200mL

[0060] Preparation Process:

[0061] Dissolve the prescribed amount of paclitaxel, soybean lecithin for injection, cholesterol, excipient D, and vitamin E in an organic solvent and pour it into a pear-shaped bottle. Rotate and evaporate the organic solvent at 30 rpm and 60°C in a water bath to make the glass bottle Form a dry film on the wall, dissolve the prescribed amount of sucrose and mannitol in 200mL of buffered saline solution, pour it into a pear-shaped bottle and rotate it at 40 rpm at room temperature (25°C) to hydrate until the dry film on the wall of the bottle is completely removed. The resulting coarse suspension was hydrated at room temperature (25° C.) for 1 hour until t...

technical field

[0001] The invention belongs to the technical field of medicine, and relates to thermosensitive liposomes, long-circulation liposomes and thermosensitive long-circulation liposome preparations of the antitumor drug paclitaxel, and also relates to preparation methods of these liposomes. Background technique

[0002] Paclitaxel is a monomeric compound with definite and strong anti-cancer effects discovered by humans in the late 20th century. Oncology has become the drug of choice.

[0003] At present, paclitaxel injection in clinical application includes domestic paclitaxel  , Taxol  , import Taxol  (USA BMS company), Anzatax  (Australian Fauliding company) and other products, these products all utilize surfactant solubilization method to solve the shortcoming that paclitaxel is insoluble in water, to reach the purpose of intravenous administration. However, these preparations have many side effects in clinical use, especially the existing commercially...

Examples

Embodiment 1

[0028] prescription:

[0029] Paclitaxel 0.4g

[0030] Soybean Lecithin for Injection 20.0g

[0031] Cholesterol 2.4g

[0032] Excipient D 5.0g

[0033] Octadecylamine 0.1g

[0034] Vitamin E 0.2g

[0035] Buffered saline solution to 200mL

[0036] Preparation Process:

[0037]Dissolve the prescribed amount of paclitaxel, soybean lecithin for injection, cholesterol, excipient D, and vitamin E in an organic solvent and pour it into a pear-shaped bottle, then add a small amount of buffered saline solution containing octadecylamine, ultrasonically make it into a uniform milk, and use a rotary evaporator The organic solvent was removed under reduced pressure to form a gel, vortexed and distilled under reduced pressure at intervals to obtain a white uniform liposome solution, and then the volume was adjusted to 200 mL with buffer solution. Then pass through the membrane (0.22 μm) under pressure to depyrogenize the entire particle, then pack into vials and freeze-dry to obtai...

Embodiment 2

[0039] prescription:

[0040] Paclitaxel 0.4g

[0041] Soybean Lecithin for Injection 20.0g

[0042] Cholesterol 2.4g

[0043] Excipient D 5.0g

[0044] Octadecylamine 0.1g

[0045] Vitamin E 0.2g

[0046] Buffered saline solution to 200mL

[0047] Preparation Process:

[0048] Dissolve the prescribed amount of paclitaxel, soybean lecithin for injection, cholesterol, excipient D, and vitamin E in an organic solvent and pour it into a pear-shaped bottle, then add a small amount of buffered saline solution containing octadecylamine, ultrasonically make it into a uniform milk, and use a rotary evaporator The organic solvent was removed under reduced pressure to form a gel, vortexed and distilled under reduced pressure at intervals to obtain a white uniform liposome solution, and then the volume was adjusted to 200 mL with buffer solution. Then pass through the membrane (0.22 μm) under pressure to depyrogenize the whole grain, pack into ampoules, freeze in the refrigerator ...

Embodiment 3

[0050] prescription:

[0051] Paclitaxel 0.4g

[0052] Soybean Lecithin for Injection 20.0g

[0053] Cholesterol 2.4g

[0054] Excipient D 5.0g

[0055] Sucrose 5.0g

[0056] Mannitol 0.1g

[0057] Octadecylamine 0.1g

[0058] Vitamin E 0.2g

[0059] Buffered saline solution to 200mL

[0060] Preparation Process:

[0061] Dissolve the prescribed amount of paclitaxel, soybean lecithin for injection, cholesterol, excipient D, and vitamin E in an organic solvent and pour it into a pear-shaped bottle. Rotate and evaporate the organic solvent at 30 rpm and 60°C in a water bath to make the glass bottle Form a dry film on the wall, dissolve the prescribed amount of sucrose and mannitol in 200mL of buffered saline solution, pour it into a pear-shaped bottle and rotate it at 40 rpm at room temperature (25°C) to hydrate until the dry film on the wall of the bottle is completely removed. The resulting coarse suspension was hydrated at room temperature (25° C.) for 1 hour until t...