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A compound pharmaceutical composition of doxorubicin and propranolol and its application

A technology of propranolol and doxorubicin, applied in the field of compound pharmaceutical composition of doxorubicin and propranolol, to achieve the effect of reducing toxic and side effects, strong anti-proliferation activity, and good clinical drug development prospects

Active Publication Date: 2020-06-26
FOSHAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Combination of doxorubicin and propranolol for the prevention and treatment of malignant tumor lymphoma has not been reported in the relevant literature almost no

Method used

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  • A compound pharmaceutical composition of doxorubicin and propranolol and its application
  • A compound pharmaceutical composition of doxorubicin and propranolol and its application
  • A compound pharmaceutical composition of doxorubicin and propranolol and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Embodiment 1: adopt Daudi cell, Raji cell and BC-3 cell to screen optimization doxorubicin (DOX) and propranolol (PRO) compound pharmaceutical composition

[0022] Take the cells in the logarithmic growth phase and inoculate 3×10 4 Cells / well were placed on a 96-well plate. After 6 hours of growth, the supernatant was discarded by centrifugation, and then administered according to the following groups: Tumor cells were divided into no drug group and drug group, and the drug group was divided into DOX and PRO single drugs. group, DOX and PRO combination group with different molar ratios, set 4-6 duplicate wells in each group, culture for 24 hours, discard the supernatant, add 100 μl of MTT (tetrazolium salt) serum-free culture medium containing 0.5 mg / ml for culture After 4 hours, add 100 μl of DMSO (dimethyl sulfoxide), place on a micro-oscillator to vibrate for 10 minutes, and then place on a microplate reader to detect the OD value at 570 nm. Results The inhibition r...

Embodiment 2

[0028] Embodiment 2: DOX and PRO joint administration effect analysis

[0029] Based on the Median-effect Principle (moderate effect principle or Chou-Talalay combined index method), the dose-response curve and the combined index curve (fa-C curve) under different effects were drawn using CombiDrug statistical software. The relationship between the effect and the combination index quantitatively evaluates whether there is a synergistic, antagonistic or additive relationship between the two drugs. Specific steps are as follows:

[0030] The drug effect is the inhibition rate (fa)=1-(the average OD570 value of the test group / the average OD570 of the tumor cell blank control group) according to the intermediate effect equation fa / fu=(D / Dm) m , take the logarithm logfa / fu=mlogD–mlogDm on both sides, set a=-mlogDm, b=m, x=logD, y=logfa / fu, and substitute into the intermediate effect equation to get y=bx–a; where fa is the drug effect , fu=1–fa, D is the drug concentration, m is t...

Embodiment 3

[0035] Example 3: Safety of DOX and PRO on peripheral blood mononuclear lymphocytes

[0036]The safety of DOX and propranolol on PBMC cells was evaluated after isolation and culture of mononuclear lymphocytes from healthy volunteers ( figure 1 ): ① draw fresh blood from healthy volunteers into a heparin anticoagulant tube (sterile); then resuspend the cells (sterile) with an equal volume of PBS (or serum-free D-Hank buffer); ② put the suspended cells Add the pre-coated human lymphocyte separation medium (preheated at 37°C), the volume ratio of lymphatic separation medium to cell suspension is not less than 1:1; ③ 500×g (or 2000rpm) horizontal centrifuge for 20-30min, room temperature (20-30°C) at slow speed; ④ Discard the upper layer of plasma, carefully suck out the middle white mist layer and add it to 5ml (or 1-2 times the volume) of PBS (or serum-free cell culture buffer), 200×g or 1000rpm Centrifuge for 10 minutes at room temperature (20-30°C) at a slow speed, discard th...

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Abstract

The invention belongs to the field of natural medicines and discloses a compound pharmaceutical composition of doxorubicin and propranolol and its application. The active ingredient of the compound pharmaceutical composition is composed of doxorubicin and propranolol in a molar ratio of 1:10-1:200. The combination of the two drugs has a strong synergistic use in treating lymphoma.

Description

technical field [0001] The invention belongs to the field of natural medicines, in particular to a compound pharmaceutical composition of doxorubicin and propranolol and its application. Background technique [0002] Cancer is a major chronic disease that seriously endangers human health, and has become the second largest killer after cardiovascular disease. Since the beginning of the 21st century, due to the rapid process of modern industrialization, environmental pollution and many other factors, the immune system of lymphocytes has been destroyed and the incidence of lymphoma has been increasing year by year. The drug system is very urgent. [0003] Doxorubicin (DOX) is an anti-tumor antibiotic that can inhibit the synthesis of RNA and DNA. It has the strongest inhibitory effect on RNA and has a wide anti-tumor spectrum. It has effects on a variety of tumors and is a non-specific cycle drug. , has a killing effect on tumor cells of various growth cycles. It is mainly a...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/704A61K31/138A61P35/00
CPCA61K31/138A61K31/704A61P35/00A61K2300/00
Inventor 刘连陈建萍刘腾李雄刘武昆崔亮彭咏波谢国健
Owner FOSHAN UNIVERSITY
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