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Vinflunine liposome preparation and preparation method of vinflunine liposome preparation

A technology of liposome preparation, Changchun Flunine, which is applied in the direction of liposome delivery, pharmaceutical formulation, medical preparations of non-active ingredients, etc., can solve the problems of increased toxicity, poor targeting, leakage, etc., and achieve reduction Vascular irritation and phlebitis, prolong half-life in vivo, and avoid phagocytosis

Inactive Publication Date: 2012-12-05
QILU PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Ordinary liposomes are quickly swallowed by the reticuloendothelial system after entering the body, and the main targets are in organs with rich reticuloendothelial systems such as liver, spleen, and bone marrow, and the targeting of other parts is poor
Moreover, it is susceptible to leakage in the body due to the action of proteins, enzymes, etc., which affects the curative effect and increases toxicity.

Method used

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  • Vinflunine liposome preparation and preparation method of vinflunine liposome preparation
  • Vinflunine liposome preparation and preparation method of vinflunine liposome preparation
  • Vinflunine liposome preparation and preparation method of vinflunine liposome preparation

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Embodiment 1

[0072] Polydispersity Index (PDI): It reflects the distribution of liposome particle size, and the smaller the value, the more concentrated the particle size distribution. Embodiment 1, passive drug loading method prepares Vinflunine liposome (comparative example)

[0073] The liposome membrane materials for encapsulating vinflunine are all: hydrogenated soybean lecithin, cholesterol and PEG-DSPE, with a mass ratio of 1:0.2:0.1.

[0074] Thin film dispersion method

[0075] Dissolve the liposome membrane material in an appropriate amount of ethanol, remove the ethanol under reduced pressure to form a dry film, add vinflunine bitartrate saline solution (4 mg / ml) to hydrate the phospholipid membrane, and obtain liposomes. The particle size is reduced to about 200nm by microfluidics.

[0076] reverse phase evaporation

[0077] Appropriate amount of dichloromethane-ether (1:1 V / V) dissolves the membrane material, adds vinflunine bitartrate normal saline solution (4mg / ml), condu...

Embodiment 2

[0081] Embodiment 2, ammonium sulfate gradient method prepares vinflunine liposome

[0082] The liposome membrane material is hydrogenated soybean phospholipid, cholesterol and PEG-DSPE, the mass ratio is 1:0.2:0.1, dissolved in an appropriate amount of ethanol, and 300mmol L of ammonium sulfate solution is added -1 , hydrated in a water bath at 60°C for 40 minutes, treated with a high-pressure homogenizer to reduce the particle size to about 200nm, then sterilized by filtration with a 0.22μm microporous membrane, and dialyzed to remove ammonium sulfate in the outer aqueous phase to obtain ammonium sulfate gradient liposomes. Add vinflunine bitartrate normal saline solution into this gradient liposome, keep the drug loaded in a water bath at 60°C for 10 minutes, and obtain vinflunine liposome after sterilization and filtration, wherein the content of vinflunine bitartrate is 2 mg / ml. After removing the free drug in the outer aqueous phase, the encapsulation efficiency was de...

Embodiment 3

[0083] Embodiment 3 pH gradient method prepares vinflunine liposome

[0084] The liposome membrane material is hydrogenated soybean phospholipid, cholesterol and PEG-DSPE, the mass ratio is 1:0.2:0.1, dissolved in an appropriate amount of ethanol, and 300mmol L of citrate buffer is added -1 , pH 4.0, hydrated in a water bath at 65°C for 20 minutes to obtain the primary product of blank liposomes; treated with a high-pressure homogenizer to reduce the particle size to 150-200 nm, and then sterilized with a 0.22 μm microporous membrane to obtain blank liposomes .

[0085] Take blank liposome suspension 10.0mL, add 500mmol·L -1 Sodium phosphate solution 6mL, mix, then add 4mg·mL -1 5 mL of vinflunine bitartrate normal saline solution was incubated at 60° C. for 10 minutes, and liposomes were prepared after sterilizing and filtering. The encapsulation efficiency was determined to be 95.4% by gel column method.

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Abstract

The invention relates to a vinflunine liposome preparation and the preparation method thereof. The vinflunine liposome preparation mainly comprises vinflunine or salt, phospholipid, cholesterin and polyethylene glycol-distearoyl phosphatidyl ethanolamine of the vinflunine, wherein salt, phospholipid, cholesterin and polyethylene glycol-distearoyl phosphatidyl ethanolamine are pharmaceutically acceptable, and the vinflunine liposome preparation can be prepared into an injection or a lyophilized preparation. The preparation method is simple in technology, easy to operate and suitable for industrial production, and long-circulating vinflunine liposomes prepared by using the method are high in encapsulation rate and good in stability.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a liposome preparation of the antitumor drug vinflunine and a preparation method thereof. Background technique [0002] Vinflunine ditartrate (vinflunine ditartrate) is a new type of semi-synthetic vinblastine developed by the French Pierre Fabre company, which exerts its anti-tumor effect by inhibiting the cell proliferation of tubulin. For the treatment of bladder cancer, non-small cell lung cancer, breast cancer and ovarian cancer. The difference between it and vinorelbine bitartrate is that two hydrogen atoms are replaced by two fluorine atoms at the C-20' position (Crit Rev Oncol Hematol.2001, 40:159-173), the structural formula of vinflunine bitartrate is as follows I show. In the in vitro anti-cancer tests of 13 human and mouse tumor models, it was found that vinflunine has better anti-cancer activity and less neurotoxicity than vinorelbine, see Eur...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K31/475A61K47/34A61P35/00A61K47/24
Inventor 王晶翼杨清敏王栋海邹伟伟张明会
Owner QILU PHARMA CO LTD
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