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Protamine oligopeptide modified paclitaxel liposome and preparation method thereof

A protamine and paclitaxel technology, which is applied in the directions of liposome delivery, medical preparations containing active ingredients, pharmaceutical formulations, etc., can solve the problem that biological macromolecules are difficult to cure, affect drug efficacy and targeting, and have poor applicability and other problems, to achieve the effect of increasing water solubility, stable product properties, and enhancing drug efficacy

Active Publication Date: 2021-05-07
INST OF BIOLOGICAL RESOURCES JIANGXI ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In recent years, many methods for preparing paclitaxel liposomes have been reported in the literature. The latest patent document with the publication number CN111329838 A uses egg yolk lecithin (the optimal ratio of phosphatidylcholine and phosphatidylethanolamine) to obtain paclitaxel with better stability. Liposomes, however, due to the natural barrier effect of the cell membrane, many biological macromolecules are difficult to enter the cells to exert curative effect, liposomes still exist and can be quickly cleared by the mononuclear phagocytosis system of the liver and spleen, and the metabolism is too fast to affect the efficacy and poor targeting
There are also reports in the literature on the use of protamine peptides combined with paclitaxel to form polymers, but the operation is complicated and the applicability is not strong
In the prior art, there is no relevant research on the modification of paclitaxel by protamine peptide binding liposome method

Method used

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  • Protamine oligopeptide modified paclitaxel liposome and preparation method thereof
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preparation example Construction

[0023] The present invention also provides a preparation method of the above paclitaxel liposome, comprising the following steps: dissolving paclitaxel, lecithin, and cholesterol in a solvent, removing the solvent after sterilization to form a film; using glucose containing protamine short peptide LMWP The membrane was washed with the solution, homogenized to obtain liposome suspension, and freeze-dried to obtain paclitaxel liposome freeze-dried powder.

[0024] The present invention has no special limitation on the type of solvent, and any type of solvent commonly used in the preparation of paclitaxel liposomes in the art can be used. In a specific embodiment of the present invention, the solvent is preferably absolute ethanol. In the present invention, the amount of absolute ethanol is calculated as lecithin, preferably 25-50mL / g lecithin, more preferably 30-45mL / g lecithin, even more preferably 35-40mL / g lecithin.

[0025] The present invention has no special limitation on ...

Embodiment 1

[0032] Accurately weigh 0.50g of paclitaxel, 15g of lecithin, 2.5g of cholesterol, dissolve in 375mL of absolute ethanol, fully stir and dissolve, after sterilizing and filtering through a 0.22μm filter element, remove the absolute ethanol by rotary evaporation to form a thin film; slowly inject 400mL of Wash the membrane with 5% protamine short peptide LMWP glucose solution, disperse for 2 minutes, and then perform homogenization treatment with dynamic high-pressure micro-jet (120MPa, 3 times) to obtain a liposome suspension; freeze the liposome suspension at -80°C Dry for 48 hours to obtain paclitaxel liposome lyophilized powder.

[0033] The particle size of the paclitaxel liposomes in the liposome suspension was measured by a potential-particle size analyzer as 124.43 nm, a dispersion coefficient of 0.8, and a zeta potential of -40.6mV. Using high performance liquid chromatography (chromatographic conditions: C 18 , water-acetonitrile 33:67 as mobile phase, flow rate 1.0m...

Embodiment 2

[0035] Accurately weigh 1.5g of paclitaxel, 30g of lecithin, 7.5g of cholesterol, dissolve in 750mL of absolute ethanol, fully stir to dissolve, after sterilizing and filtering through a 0.22μm filter element, remove the absolute ethanol by rotary evaporation to form a thin film; slowly inject 500mL of 2 Wash the membrane with a glucose solution of % protamine short peptide LMWP, disperse for 3 minutes, and then perform homogenization treatment with dynamic high-pressure micro-jet (200MPa, 5 times) to obtain a liposome suspension; freeze-dry the liposome suspension at -80°C 48h to obtain paclitaxel liposome lyophilized powder.

[0036]Using the same assay method as in Example 1, the encapsulation efficiency of paclitaxel liposomes was 92%, the average particle size was 121.17 nm, the dispersion coefficient was 0.85, and the zeta potential was -38.4mV.

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Abstract

The invention provides a protamine oligopeptide modified paclitaxel liposome and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The protamine oligopeptide modified paclitaxel liposome provided by the invention comprises the following raw materials of protamine oligopeptide LMWP, paclitaxel, lecithin, cholesterol and glucose. The protamine oligopeptide LMWP is combined with a liposome embedding technology, the operation is simple and convenient, the obtained paclitaxel liposome is stable in property and high in bioavailability, the average particle size is about 124.43 nm and is smaller than that of a common paclitaxel liposome, the zeta potential is -40.6 mV, and the storage stability is good. The water solubility of the protamine oligopeptide modified paclitaxel liposome is improved, the content of the paclitaxel liposome in cells is also increased accordingly, the paclitaxel liposome has the effect of enhancing the drug effect, and protamine can obviously reduce the density of blood vessels in tumors and has the anti-tumor effect.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a paclitaxel liposome modified by a protamine short peptide and a preparation method thereof. Background technique [0002] Paclitaxel compounds belong to diterpenoid alkaloids and are one of the plant-derived antitumor drugs known to have good curative effects. It has obvious anti-cancer activity against a variety of malignant tumors, including ovarian cancer, non-small cell lung cancer, gastric cancer, head and neck tumors and other malignant tumors. Paclitaxel has poor water solubility, and its solubility in water is <0.03g / L. Therefore, it is necessary to add polyoxyethylene castor oil and an appropriate amount of absolute ethanol as solubilizers to paclitaxel injections, and use polyoxyethylene castor oil as a solubilizer, there is a 40% probability It can cause severe allergic reactions, which prevents it from being effectively promoted i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/42A61K31/337A61P35/00
CPCA61K9/127A61K47/42A61K31/337A61P35/00
Inventor 蔡力创涂越刘建平欧阳克氙郭雄昌
Owner INST OF BIOLOGICAL RESOURCES JIANGXI ACAD OF SCI
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