Unlock instant, AI-driven research and patent intelligence for your innovation.

Preparation method of microlipid granule for wrapping medicine

A manufacturing method and technology of liposomes, applied in drug combination, drug delivery, pharmaceutical formulation, etc., can solve the problems of reducing curative effect, precipitation, leakage, etc., and achieve the effects of improving curative effect, avoiding agglutination, increasing stability and storage period

Inactive Publication Date: 2002-11-20
TAIWAN LIPOSOME CO LTD
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The early liposomes used natural lipids as raw materials, but the natural lipids contained negatively charged phospholipids, which made the surface of the liposomes negatively charged, similar to the decomposition particles produced during apoptosis, and injected into the blood circulation When it is released, it will be quickly swallowed by the mononuclear phagocytic system or the reticuloendothelial system (RES); high-density lipoprotein (HDL) in the blood will also remove the phospholipids of the liposomes composed of natural lipids, so that The disintegration of the liposomes causes the drug to leak from the liposomes, which reduces the half-life of the drug circulation and reduces the curative effect; when the neutral liposomes are stored, they will coagulate due to peptization, causing precipitation and shortening the validity period of the drug
[0005] It is disclosed in U.S. Patent 5013556 that adding 1-20% (moles) of polyalkyl ether lipids can prolong the time of liposomes in the blood circulation and increase the drug effect, but experimental data shows: with high phase transition temperature and high cholesterol content When making liposomes with a diameter of 50-100nm to encapsulate the anticancer drug ezyme, a larger amount of polyalkyl ether lipids is used to prolong the time of liposomes in the blood circulation, which will reduce the accumulation of anticancer drugs in the tumor site amount, and reduce the efficacy

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0012] Example 1: Preparation of liposomes coated with ammonium sulfate:

[0013] Unilamellar vesicles were fabricated using standard film hydration and repeated extrusion methods. Dipamitoylphosphatidyl choline (DPPD)], distearyl phosphatidyl choline (DSPC) and cholesterol [Cholesterol (Chol] (for example: distearyl Acid phosphocholine: cholesterol is 3: 2 or dipalmitate phosphocholine: cholesterol is 3: 2, the mole ratio) is dissolved in chloroform. After mixing, remove the solvent with a desiccator under reduced pressure, and then add 150mM [ Ammonium sulfate (NH 4 ) SO 4 ], pH 5.0, hydrated at 55°C, and the uniform mixture was repeatedly frozen and thawed five times with liquid nitrogen and a water bath, then filtered five times with a 0.1 μm polycarbonate filter membrane with a squeezer at 60°C, and then Filter five times with a 0.05 μm filter membrane to make ammonium sulfate-coated liposomes.

Embodiment 2

[0014] Embodiment 2: Preparation of liposomes encapsulating doxorubicin:

[0015] Ammonium sulfate-coated liposomes were used to remove sulfuric acid outside the liposomes with a molecular sieve column (Sephadex G-50, Pharmacia), and 1 mg of ezyme was added to every 10 μmole of phosphate lipid, heated to 60°C and shaken (100 rpm) for 30 Minutes, then rapidly cooled with ice cubes for 3 minutes, after cooling down, remove the epsin outside the liposomes with a molecular sieve column, and use a pH7.2 buffer (100mM DEPES, 144mM NaCl, pH7.2) or 0.9% sodium chloride solution, and the liposome part was collected to complete the preparation of the liposome. The completed liposomes were filtered with a 0.22 μm filter membrane and argon gas was passed through to facilitate preservation.

Embodiment 3

[0016] Embodiment 3: Preparation of liposomes encapsulating topotecan (topotecan):

[0017] Use a molecular sieve column (Sephadex G-50, Pharmacia) to remove the ammonium sulfate outside the liposomes, add 1 mg of topogen per 10 μmole of phosphate, heat to 60°C and shake (100rpm) 30 minutes, then rapidly cooled with ice cubes for 3 minutes, after cooling, use a molecular sieve column to remove the topogens outside the vesicles, and use a pH7.2 buffer solution (100mM DEPES, 144mM Nacl, pH7.2) for the eluent Or 0.9% sodium chloride solution, collect the liposome part, that is, complete the preparation of the liposome, and filter the completed liposome with a 0.22 μm filter membrane, and pass through argon gas to facilitate preservation.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
diameteraaaaaaaaaa
Login to View More

Abstract

The preparation method of liposome for wrapping medicine is characterized by that in the course of preparing liposome or after the production of liposome or when the liposome is used to wrap the medicine 0.01-1.0% (gram-molecule) of polyalkyl ether lipid is added so as to make them into the invented liposome wrapping medicine capable of preventing liposome from agglutinating and precipitating. Said polyalkyl ether lipid is formed from two portions of polyalkyl ether and lipid, and the molecular weight of polyalkyl ether is 200-20000. It can increase stability of liposome medicine preparation and its storage time, and can raise therapeutic effect of medicine.

Description

technical field [0001] The invention relates to the technical field of pharmacy, in particular to a method for manufacturing drug-coated liposomes. Background technique [0002] It is well known that liposomes are tiny vesicles composed of one or several layers of lipid bilayer membranes, which are good dosage forms for drug delivery, and have four main advantages: [0003] 1. Liposomes are composed of phospholipids, which have the same composition as cell membranes, can be decomposed in vivo, are not toxic, do not cause immune reactions, and can be used multiple times; 2. Drugs encapsulated in liposomes will be Control the speed of slow release, change the kinetics of the drug, and increase the efficacy of the drug; 3. Highly toxic drugs are encapsulated in liposomes, which can reduce adverse side effects. 4. The lipid composition, particle size, structure or preparation method of the vesicles are more selective to the encapsulated drug. [0004] The early liposomes used ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K9/50A61K9/52A61K31/70A61P35/00
Inventor 郑瑞菁
Owner TAIWAN LIPOSOME CO LTD