Picane maleate agar liposome and preparation method thereof

A technology of picentan maleate and liposome, applied in the field of medicine, can solve the problems of inability to prepare samples, low encapsulation efficiency, drug leakage, etc., and achieve excellent anti-tumor effect, reduce toxic reactions, and be safe and reliable. Effect

Active Publication Date: 2018-03-16
北京博恩特药业有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In the patent CN103479578A, the encapsulation efficiency of the liposomes prepared by the pH gradient method is high, but due to the introduction of new buffer salt particles, the risk of clinical drug use is increased; at the same time, the ammonium sulfate gradient method studied in this patent cannot be prepared to meet clinical needs. For samples, the encapsulation efficiency is lower than 10%
Another patent CN1382039A adopts the method of passive drug loading, directly adds picantron solution to the phospholipid membrane for hydration, and the encapsulation efficiency is only 85%, and the drug is easy to leak from the liposome, which has not reached the goal of reducing the toxic reaction of picantron injection. Purpose

Method used

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  • Picane maleate agar liposome and preparation method thereof
  • Picane maleate agar liposome and preparation method thereof
  • Picane maleate agar liposome and preparation method thereof

Examples

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experiment example

[0030] The encapsulation efficiency of the liposomes prepared by the different methods of Examples 1-9 of the present invention is shown in Table 1. In Example 5, dialysis was used to remove the ammonium sulfate solution in the external aqueous phase. Although the encapsulation efficiency reached 89.6%, it was not suitable for industrial production. In Examples 7 and 8, a buffer was used to adjust the pH value, and the liposome encapsulation efficiency was only 4%. Embodiment 9 adopts high-pressure homogenizer-extruder to prepare the liposome particle diameter of Picetaxel Maleate to be 87.29nm, uniform particle size distribution, distribution width 40.15, potential-9.06mV, the results are shown in figure 1 and figure 2 .

[0031] The encapsulation efficiency of the Picetaxel maleate liposome prepared in the embodiment of table 1

[0032]

Embodiment 1

[0034] (1) Film formation: Weigh 300.2mg of DSPC, 100.2mg of CHO, 99.8mg of DSPE-PEG20000, dissolve in 10mL of chloroform, heat to dissolve, remove the chloroform by evaporating under reduced pressure on a rotary evaporator at 55°C, and obtain lipid film;

[0035] (2) Hydration: add 26mL of 0.2mol / L ammonium sulfate solution to the lipid film, and hydrate at 55°C for 30min to obtain the primary blank liposome;

[0036] (3) Sizing: Ultrasonic disperse the blank liposome primary product on an ultrasonic disperser for 4 minutes with a power of 600-800w. After sizing, filter with a 0.45-micron microporous membrane for 3 times and a 0.22-micron microporous membrane for 1 time. , to obtain blank liposome 24mL;

[0037] (4) Manufacturing liposome transmembrane gradient inside and outside: adopt ultrafiltration method, replace the ammonium sulfate solution of blank liposome external water phase with 9% sucrose solution, replace 7 times, obtain blank liposome 20mL;

[0038] (5) Drug ...

Embodiment 2

[0041] (1) Oil phase: Weigh 450.6mg of DSPC, 150.3mg of CHO, and 149.9mg of DSPE-PEG2000, dissolve in 3.9mL of absolute ethanol, heat to dissolve, and keep warm at 55°C for 30min;

[0042] (2) Water phase: prepare 39 mL of 0.2 mol / L ammonium sulfate aqueous solution, and keep it warm at 55 °C for 30 min;

[0043] (3) Emulsification: inject the oil phase into the water phase at 55°C, and stir continuously with a magnetic stirrer until the absolute ethanol is completely volatilized to obtain 37 mL of blank liposome;

[0044](4) Sizing: Ultrasonic disperse the blank liposome primary product on an ultrasonic disperser for 4 minutes with a power of 600-800w. Filter once to obtain 35 mL of blank liposomes;

[0045] (5) Manufacturing liposome transmembrane gradient inside and outside: adopt ultrafiltration method, replace the ammonium sulfate solution of blank liposome external water phase with 9% sucrose solution, ultrafilter 7 times, obtain blank liposome 30.8mL;

[0046] (6) Dru...

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Abstract

The invention discloses a maleic acid pixantrone liposomal and a preparing method thereof. Pixantrone common injection is prepared into the liposomal so that the toxic and side effects can be relieved, and the medicinal effect can be better performed. The problem that the encapsulation efficiency is low when liposomal is prepared through an ammonium sulfate gradient method is solved. The particle size of the hollow liposomal can be better controlled through a high pressure homogenizing-extruding machine, and particles are evenly distributed. It is verified for a long time that the method for preparing the liposomal through the ammonium sulfate gradient method is good in safety, the preparing technology is simple, the encapsulation efficiency of the liposomal is high, and the method is suitable for industrial production.

Description

technical field [0001] The invention relates to a liposome of picantecone maleate and a preparation method thereof, belonging to the technical field of medicine. Background technique [0002] Pixantrone dimaleate, a cytotoxic azaxanthedione and weak topoisomerase II inhibitor, was approved by the European Union in 2012 for the treatment of adults with relapsed or refractory aggressive non-Hodgkin B-cell lymphoma , trade name Pixuvri. The mother nucleus of picantron is mitoxantrone. Years of clinical application have shown that mitoxantrone has obvious toxic side effects, especially those related to bone marrow suppression and cardiotoxicity, while animal experiments of picantron have not shown It has measurable cardiotoxicity, less cytotoxicity and myelosuppression, and has obvious antitumor activity in different tumor models, especially in leukemia and lymphoma models, which is always superior to mitoxantrone and doxorubicin. The free form of picantone is unstable, so it ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K31/473A61P35/00
CPCA61K9/1271A61K31/473
Inventor 郭光明佟志远王海燕
Owner 北京博恩特药业有限公司
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