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Biological endophilic ligand numerator mediated target liposome, preparation and uses thereof

A technology targeting liposomes and affinity, which is applied in liposome delivery, organic active ingredients, medical preparations of non-active ingredients, etc., which can solve the problems of low antibody affinity, fast clearance, and high cost

Inactive Publication Date: 2008-12-10
INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although immunoliposomes have good prospects in targeted therapy, there are still some shortcomings, such as relatively high cost, low affinity of some antibodies, poor stability, rapid clearance in the body, and certain heterogeneity etc., need further research

Method used

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  • Biological endophilic ligand numerator mediated target liposome, preparation and uses thereof
  • Biological endophilic ligand numerator mediated target liposome, preparation and uses thereof
  • Biological endophilic ligand numerator mediated target liposome, preparation and uses thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0050] Preparation prescription (25 ml capacity)

[0051] TAX 50mg

[0052] EPC 1850mg

[0053] Targeted Phospholipids 75mg

[0054] DSPG 75mg

[0055] Sucrose 2500mg

[0056] Preparation process one:

[0057] Add EPC, targeted phospholipids and DSPG into a round bottom flask according to the prescription ratio, add dichloromethane-methanol-water mixed solvent to dissolve, and remove the solvent by rotary evaporation under reduced pressure at 45°C. The phospholipid forms a film on the inner wall of the round bottom flask, and the prepared film is dried under vacuum for 20 hours to ensure that the organic solvent is completely removed. Add PBS buffer (Ph6.5) to the prepared film, hydrate at 45-60°C for 1 hour to obtain multilamellar liposomes (MLVs), and pass the prepared MLVs sequentially through the pores at a temperature greater than 45°C and high pressure On polycarbonate membranes of 200nm, 100nm, and 80nm, obtain large unilamellar liposomes (LUVs) with a particle si...

Embodiment 2

[0067] prescription:

[0068] TAX 50mg

[0069] EPC 1950mg

[0070] Targeted Phospholipids 25mg

[0071] CHOL 50mg

[0072] Lactose 1250mg

[0073] Preparation Process:

[0074] Add EPC and targeted phospholipids into a round bottom flask according to the prescription ratio, add dichloromethane / chloroform-methanol-water mixed solvent to dissolve, and remove the solvent by rotary evaporation under reduced pressure at 45°C. The phospholipid forms a film on the inner wall of the round bottom flask, and the prepared film is dried under vacuum for 20 hours to ensure that the organic solvent is completely removed. Add PBS (Ph6.5) to the prepared film and hydrate at 45-60°C for 1 hour to obtain multilamellar liposomes (MLVs) with a phospholipid concentration of 50 mg / ml, which will be prepared under high-pressure conditions at a temperature greater than 45°C The MLVs are in, pass through polycarbonate membranes with pore sizes of 200nm, 100nm, and 80nm in turn to obtain large u...

Embodiment 3

[0078] Preparation prescription (25ml capacity):

[0079] TAX 50mg

[0080] EPC 1600mg

[0081] Targeted Phospholipids 100mg

[0082] DPPG 25mg

[0083] PEG2000-DSPE 280mg

[0084] Mannitol 3750mg

[0085] Preparation process one:

[0086] Add the phospholipid into the round bottom flask according to the recipe ratio, add dichloromethane-methanol-water mixed solvent to dissolve, and remove the solvent by rotary evaporation under reduced pressure at 45°C. The phospholipid forms a film on the inner wall of the round bottom flask, and the prepared film is dried under vacuum for 20 hours to ensure that the organic solvent is completely removed. Add PBS buffer (Ph6.5) to the prepared film, and hydrate at 45-60°C for 1 hour to obtain multilamellar liposomes (MLVs), with a phospholipid concentration of 50 mg / ml. The prepared MLVs pass through polycarbonate membranes with apertures of 200nm, 100nm, and 80nm successively to obtain large unilamellar liposomes (LUVs) with a particle...

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Abstract

The invention discloses a targeted liposome mediated by the ligand molecule with biological affinity, and a preparation as well as the application thereof. The targeted liposome of antitumor drug prepared by the invention has little toxicity, good tolerance for patients and enhanced water-solubility and stability. And the invention also discloses the processing technique of the preparation. Freeze-dry liposome consists of natural or synthetic phospholipid, charged phospholipid, target material, antitumor drugs, buffer solution and freeze-drying protective agent. The processing technique comprises the procedures of the preparation of phospholipid membrane of the antitumor drug, the homogenization of the liposome, the addition of the freeze-drying protective agent, volume metering, sterilizing, split charging, freeze-drying and storage, etc. The liposome is kept under room temperature for 12 months with good stability. The entrapment rate of the liposome is over 90 percent. The granule diameter of the liposome is within 50 to 300mm. The liposome has little toxic and side effects and simple technique, thus facilitating the commercial process of the liposome.

Description

field of invention [0001] The invention relates to a targeted liposome preparation, in particular to a targeted liposome mediated by a class of bio-affinity ligand molecules, and also relates to the preparation and application of the liposome. Background technique [0002] Liposome was first discovered by British scholar Bangham in 1965 when phospholipids were dispersed in water for electron microscope observation. Phospholipids are dispersed in water to naturally form multilayered vesicles, and each layer is a lipid bilayer structure; the center of the vesicle and each layer are separated by water, and the thickness of the bilayer is about 4nm. Later, this bilayer vesicle with a similar biological membrane structure was called liposome. Liposome is a new type of targeted microparticle drug delivery carrier, which contains at least one vesicle containing an inner water phase composed of a phospholipid bilayer membrane. Liposomes are generally divided into: Small unilamella...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K9/19A61K47/48A61K47/24A61K47/34A61K31/337A61K31/704A61P35/00A61K47/60
Inventor 梅兴国杨媛梅丹宇
Owner INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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