Mitoxantrone and berberine composition and application thereof in preparation of anti-tumor drugs

A technology of mitoxantrone and a composition is applied in the application field of a mitoxantrone and berberine composition in reducing the cardiotoxicity of mitoxantrone, and achieves easy industrialization, good stability, and reduced cardiotoxicity. Effect

Inactive Publication Date: 2020-12-22
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In the prior art, there is no report that the combination of mitoxantrone and berberine is used to prepare antitumor drugs, and there is no relevant report that the combination of the two can reduce cardiotoxicity

Method used

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  • Mitoxantrone and berberine composition and application thereof in preparation of anti-tumor drugs
  • Mitoxantrone and berberine composition and application thereof in preparation of anti-tumor drugs
  • Mitoxantrone and berberine composition and application thereof in preparation of anti-tumor drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1: In vitro cytotoxicity test

[0042] MTT (thiazolium blue) method was used to screen the synergistic ratio of mitoxantrone and berberine to mouse breast cancer (4T1) cells.

[0043] Dilute 4T1 cells with culture medium to a density of 1×10 4 cells / mL, and inoculated in a 96-well plate, 100 μL per well. After overnight incubation in the incubator, discard the old culture medium, add different concentrations of mitoxantrone hydrochloride solution, berberine hydrochloride solution and different ratios of mitoxantrone hydrochloride-hydrochloride diluted with fresh culture medium to each well The berberine mixed solution was placed in an incubator and incubated for 48 hours. Afterwards, the cell viability at each concentration was calculated by the MTT method. The combination index (CI) of mitoxantrone and berberine was calculated by the Chou-Talalay method, and the characteristics of their combined effects were investigated. The formula for calculating CI is: ...

Embodiment 2

[0047]MTT method was used to screen the synergistic ratio of mitoxantrone and berberine on mouse leukemia (L1210) cells.

[0048] This example is the same as Example 1, except that the density of L1210 cells after dilution is 3×10 4 cells / mL, see the experimental results figure 2 . The experimental results showed that the synergistic effect of mitoxantrone and berberine on 4T1 cells was not exactly the same as that of L1210 cells, and the mass ratio of mitoxantrone: berberine in the range of 1:2-1:10 showed a relatively strong effect. Good synergy.

Embodiment 3

[0049] Embodiment 3: Preparation of double drug-loaded liposomes

[0050] The preparation method of the double drug-loaded liposome of the present embodiment comprises the following steps:

[0051] (1) Weigh hydrogenated soybean lecithin, cholesterol, methoxy-polyethylene glycol 2000-distearoylphosphatidylethanolamine (mass ratio 3:1:1), add chloroform to dissolve, and evaporate under reduced pressure to remove the organic solvent to form a dry lipid film;

[0052] (2) After adding 300mM ammonium sulfate solution and hydrating at 65°C for 30min, carry out granulation through polycarbonate membrane to form nano-sized small unicellular liposomes with ammonium sulfate solution inside and outside the liposome membrane;

[0053] (3) above-mentioned small unicellular liposomes are passed through the agarose CL-4B gel column equilibrated with the PBS solution (pH 7.5) of 10mM histidine in advance to form ammonium sulfate gradient blank liposomes;

[0054] (4) Drug loading process: ...

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Abstract

The invention belongs to the technical field of medicines, relates to application of a mitoxantrone and berberine composition in preparation of anti-tumor drugs, and also relates to application of themitoxantrone and berberine composition in reduction of mitoxantrone cardiotoxicity. The composition contains mitoxantrone or salt thereof, and berberine or salt thereof. In the pharmaceutical composition, the mass ratio of the mitoxantrone or the salt thereof to the berberine or the salt thereof is (10:1)-(1:10), preferably (2:1)-(1:10). The invention also provides double-drug-loading liposome ofthe composition. The double-drug-loading liposome has relatively high drug loading capacity, and two drugs can be maintained in a synergistic effect proportion range for a long time in a blood circulation process, so that the synergistic proportion delivery at tumor tissues is favorably realized, and the anti-tumor effect is further improved. The cardiotoxicity of a patient to the mitoxantrone can be further reduced, and higher safety is achieved.

Description

【Technical field】 [0001] The invention belongs to the technical field of medicine, relates to a composition of mitoxantrone and berberine and its application in the preparation of antitumor drugs, and also relates to the use of the composition of mitoxantrone and berberine in reducing cardiotoxicity of mitoxantrone Applications. 【Background technique】 [0002] Combination chemotherapy refers to the simultaneous administration of two or more chemotherapy drugs. Through the synergistic or additive effect of multiple drugs, the anti-tumor effect of drugs can be enhanced, while the toxic side effects of drugs can be reduced, multi-drug resistance can be overcome, and the prognosis of patients can be improved. Combination chemotherapy has now played a pivotal role in cancer treatment, and many researchers are working on precise drug delivery using defined drug ratios. So far, liposome is the only nano drug delivery system based on combination drug delivery platform approved by ...

Claims

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Application Information

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IPC IPC(8): A61K31/136A61K31/4375A61K9/127A61P35/00A61P9/00
CPCA61K9/127A61K31/136A61K31/4375A61K47/24A61P9/00A61P35/00A61K2300/00
Inventor 王永军杨子蒙何仲贵刘洪卓赵立文
Owner SHENYANG PHARMA UNIVERSITY
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