Lung-targeted medicine carrying precursor liposome for injection and method of use thereof

Abstract

The invention relates to the technical field of medicament delivery by a carrier, in particular to a lung targeting medicament carried proliposome used for injection and an application method thereof. Solid dispersion technology is adopted to obtain solution A by dissolving active medicament, phospholipid liposome, cholesterol liposome, surface active agent and acid type carrier in absolute ethyl alcohol or the mixed solvent of absolute ethyl alcohol and absolute ether; active carbon which is used for injection and has the volume being 0.1-1% of the volume of the solution A is added into the solution A; stirring, standing and filtering of the solution by a millipore filter are carried; therefore, aseptic solution B free of pyrogen is obtained; aseptic additives are added into the solution B under an aseptic condition; organic solvent is removed; and solid granular medicament carried proliposome or powdered medicament carried proliposome are obtained. The invention has the advantages that the preparation process is simple; the cost is low; the quality is controllable; the stability is good; and the invention is suitable for industrial production. The medicament carried proliposome prepared by effervescency dispersion technology has small and uniform particle diameter, the electric charge ranges from -10mv to -30mv, the proliposome can deliver over 90% medicament to a lung, and remarkable lung targeting effect is achieved, and thus being the best preparation delivering medicament by a carrier for treating lung diseases.

Description

technical field

[0001] The invention relates to the technical field of pharmaceutical carrier administration, in particular to the lung-targeted drug-loaded proliposome for injection and its application method. Background technique

[0002] Liposome refers to a bimolecular vesicle with a structure similar to a biological membrane. It is a multilayered vesicle naturally formed by phospholipids dispersed in water. Each layer is a lipid bilayer. Separated by a water phase, the thickness of the bilayer is about 4 nm. It was first discovered by British Bangham and Standish in the 1960s when phospholipids were dispersed in water and observed with an electron microscope. In 1971, British Liman et al. began to use liposomes as drug carriers. Liposome is the most promising targeted drug delivery carrier in pharmacy. It can embed drug powder or solution in particles with a diameter of nanometer or micrometer. This particle has a cell-like structure and can enter the body to change T...

Examples

Embodiment 1

[0093] Example 1: The lung-targeted drug-loaded proliposome for injection is prepared by the following steps:

[0094] a. Take the following materials in the following proportions by weight:

[0095] Docetaxel 4mg

[0096] Dicetyl Phospholipids 10mg

[0097] Hydrogenated Soy Lecithin 20mg

[0098] Cholesterol 15mg

[0099] Tween-80 20mg

[0100] Citric acid 90mg

[0101] And the above-mentioned substances were dissolved in absolute ethanol to obtain a 10% (mg / ml) solution A;

[0102] b. Add 0.5% of its volume of activated carbon for injection into solution A, stir and let it stand, and filter through a microporous membrane with a pore size of 0.22 μm to obtain sterile and pyrogen-free solution B;

[0103] c. Under sterile conditions, add 3 mg of polyvinylpyrrolidone solution B, and then remove the organic solvent under reduced pressure under general mechanical stirring to obtain solid granular drug-loaded proliposomes;

[0104] d. Determining the main drug content of th...

Embodiment 2

[0107] Example 2: The lung-targeted docetaxel proliposome for injection is prepared by the steps in the following sequence:

[0108] a. Take the following materials in the following proportions by weight:

[0109] Docetaxel 0.001mg

[0110] Soy Lecithin 15mg

[0111] Phosphatidylserine 8mg

[0112] Cholesterol 10mg

[0113] Tween-80 20mg

[0114] Tartaric acid 60mg

[0115] Citric acid 10mg

[0116] And the above-mentioned substances were dissolved in absolute ethanol to obtain a 5% (mg / ml) solution A;

[0117] b. Add 0.1% of its volume of activated carbon for injection to solution A, stir and let it stand, and filter with a microporous membrane with a pore size of 0.15 μm to obtain sterile and pyrogen-free solution B;

[0118] c. Under sterile conditions, add 2 mg of vitamin E, 5 mg of mannitol and 3 mg of polyvinyl rolidone into solution B, and then remove the organic solvent under reduced pressure with general mechanical stirring to obtain solid granular polyvinyl ro...

Embodiment 3

[0122] Example 3: The lung-targeted docetaxel proliposome for injection is prepared by the steps in the following sequence:

[0123] a. Take the following materials in the following proportions by weight:

[0124] Docetaxel 8mg

[0125] Lecithin 30mg

[0126] Beta-Sitosterol 15mg

[0127] Tween-80 15mg

[0128] Tartaric acid 25mg

[0129] And the above-mentioned substances were dissolved in a mixed solvent of absolute ethanol and absolute ether, the volume ratio of absolute ethanol and absolute ether in the mixed solvent was 7:3, and a solution A of 30% (mg / ml) was obtained;

[0130] b. Add 0.3% of its volume of activated carbon for injection into solution A, stir and let it stand, and filter with a microporous membrane with a pore size of 0.18 μm to obtain sterile and pyrogen-free solution B;

[0131] c. Under sterile conditions, 5 mg of vitamin E was added to solution B, and then the organic solvent was removed by a closed-loop spray drying device to obtain powdered docet...

technical field

[0001] The invention relates to the technical field of pharmaceutical carrier administration, in particular to the lung-targeted drug-loaded proliposome for injection and its application method. Background technique

[0002] Liposome refers to a bimolecular vesicle with a structure similar to a biological membrane. It is a multilayered vesicle naturally formed by phospholipids dispersed in water. Each layer is a lipid bilayer. Separated by a water phase, the thickness of the bilayer is about 4 nm. It was first discovered by British Bangham and Standish in the 1960s when phospholipids were dispersed in water and observed with an electron microscope. In 1971, British Liman et al. began to use liposomes as drug carriers. Liposome is the most promising targeted drug delivery carrier in pharmacy. It can embed drug powder or solution in particles with a diameter of nanometer or micrometer. This particle has a cell-like structure and can enter the body to change T...

Examples

Embodiment 1

[0093] Example 1: The lung-targeted drug-loaded proliposome for injection is prepared by the following steps:

[0094] a. Take the following materials in the following proportions by weight:

[0095] Docetaxel 4mg

[0096] Dicetyl Phospholipids 10mg

[0097] Hydrogenated Soy Lecithin 20mg

[0098] Cholesterol 15mg

[0099] Tween-80 20mg

[0100] Citric acid 90mg

[0101] And the above-mentioned substances were dissolved in absolute ethanol to obtain a 10% (mg / ml) solution A;

[0102] b. Add 0.5% of its volume of activated carbon for injection into solution A, stir and let it stand, and filter through a microporous membrane with a pore size of 0.22 μm to obtain sterile and pyrogen-free solution B;

[0103] c. Under sterile conditions, add 3 mg of polyvinylpyrrolidone solution B, and then remove the organic solvent under reduced pressure under general mechanical stirring to obtain solid granular drug-loaded proliposomes;

[0104] d. Determining the main drug content of th...

Embodiment 2

[0107] Example 2: The lung-targeted docetaxel proliposome for injection is prepared by the steps in the following sequence:

[0108] a. Take the following materials in the following proportions by weight:

[0109] Docetaxel 0.001mg

[0110] Soy Lecithin 15mg

[0111] Phosphatidylserine 8mg

[0112] Cholesterol 10mg

[0113] Tween-80 20mg

[0114] Tartaric acid 60mg

[0115] Citric acid 10mg

[0116] And the above-mentioned substances were dissolved in absolute ethanol to obtain a 5% (mg / ml) solution A;

[0117] b. Add 0.1% of its volume of activated carbon for injection to solution A, stir and let it stand, and filter with a microporous membrane with a pore size of 0.15 μm to obtain sterile and pyrogen-free solution B;

[0118] c. Under sterile conditions, add 2 mg of vitamin E, 5 mg of mannitol and 3 mg of polyvinyl rolidone into solution B, and then remove the organic solvent under reduced pressure with general mechanical stirring to obtain solid granular polyvinyl ro...

Embodiment 3

[0122] Example 3: The lung-targeted docetaxel proliposome for injection is prepared by the steps in the following sequence:

[0123] a. Take the following materials in the following proportions by weight:

[0124] Docetaxel 8mg

[0125] Lecithin 30mg

[0126] Beta-Sitosterol 15mg

[0127] Tween-80 15mg

[0128] Tartaric acid 25mg

[0129] And the above-mentioned substances were dissolved in a mixed solvent of absolute ethanol and absolute ether, the volume ratio of absolute ethanol and absolute ether in the mixed solvent was 7:3, and a solution A of 30% (mg / ml) was obtained;

[0130] b. Add 0.3% of its volume of activated carbon for injection into solution A, stir and let it stand, and filter with a microporous membrane with a pore size of 0.18 μm to obtain sterile and pyrogen-free solution B;

[0131] c. Under sterile conditions, 5 mg of vitamin E was added to solution B, and then the organic solvent was removed by a closed-loop spray drying device to obtain powdered docet...

Images