Novel combined drugs for treating Aids and screening method thereof

A screening method and anti-AIDS technology, applied in biostatistics, bioinformatics, special data processing applications, etc., can solve problems such as unbearable side effects of high-dose drugs, and achieve great clinical value

Inactive Publication Date: 2016-07-06
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The reason for the unfortunate death of many patients may not be from the disease itself, but from the inability to bear the huge toxic and side effects of high-do...

Method used

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  • Novel combined drugs for treating Aids and screening method thereof
  • Novel combined drugs for treating Aids and screening method thereof
  • Novel combined drugs for treating Aids and screening method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Single drug effect and dosage experiment

[0039] The following 8 anti-AIDS drugs were included in the experimental drug candidates: Zidovudine (AZT), Lamivudine (3TC), Tenofovir (TDF), Abacavir (Abacavir, ABC), efavirenz (EFV), nevirapine (Nevirapine, NVP), lopinavir, ritonavir (Lopinavir, LPV) and lattigravir (Raltigravir, RAL). These eight drugs are anti-AIDS drugs with different therapeutic mechanisms and potential synergistic effects, and their different therapeutic mechanisms are shown in Table 1:

[0040] Table 1 Eight anti-AIDS drugs with different therapeutic mechanisms

[0041]

[0042] Feedback System Control (FSC) technology (US Patent No.: US8232095B2), a patented technology in the United States, is a platform technology for the optimization of combined drugs. A small number of experimental drug combinations are designed through statistical methods to calibrate the synergy between multiple drugs. Antagonism [1-7]. The FSC platform consists of four mod...

Embodiment 2

[0052] Experimental design and experimental testing and analysis of drug combinations

[0053] According to the papers previously published by the laboratory (HongquanXu*, JessicaJaynesandXiantingDing, "CombiningTwo-LevelandThree-LevelOrthogonalArraysforFactorScreeningandResponseSurfaceExploration", StatisticaSinica, Volume: 24Pages: 269-289 (2014)), an effective experimental design method called (CompositeOrthogonalDesign(CompositeArrayDesign OACD), in which, the experimental design scheme of 8-drug combination therapy is directly given. In this example, the experimental design scheme in the above-mentioned experimental design means was adopted, and 58 drug combinations were designed for experiments. The experimental results constructed the relationship between the dose, ratio and efficacy of the combined drugs through statistical modeling.

[0054] 1. Through the statistical experimental design method of Orthogonal Array Composite Design (OACD), 58 combination drugs were de...

Embodiment 3

[0092] Through the fitting model of Example 2, systematically study the efficacy of multi-drug combinations

[0093] Because the drug EFV is very commonly used in clinic, and has common side effects, such as headache and nausea. Moreover, the existing drug regimens of EFV have generally produced drug resistance. The values ​​of HIV infection rate were recorded by different selections of drug doses in the model. Analysis results suggest:

[0094] 1) The most effective 4-drug combination containing EFV drugs: [TDF+AZT+EFV+3TC], [LPV+ABC+AZT+EFV] and [LPV+ABC+EFV+3TC]. These combinations have greater than 95% virus inhibitory effect on cellular antiviral models.

[0095] 2) The most effective 4-combination drugs that do not contain EFV drugs: [TDF+LPV+3TC+RAL] and [LPV+AZT+3TC+NVP]. These combinations have greater than 95% virus inhibitory effect on cellular antiviral models.

[0096] Among them, the dose relationship of TDF+AZT+EFV+3TC is: 1:6:1:180; the dose relationship o...

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Abstract

The invention discloses an anti-Aids combined drug screening method. The method comprises the following steps: measuring the cytotoxicity, toxicity median dose and effect median dose of a single drug; deciding the drug dose of each drug in the combined drug experiment; designing combined drugs through an experiment design way; carrying out experimental test on the combined drugs on a virus infected cell model so as to measure a cytotoxicity suppression ratio; establishing a virus suppression ratio and a dose response curve of combined treatment of the combined drugs, and fitting data to obtain a fitting model; and carrying out analysis to obtain the effective combined drugs. The method is capable of effectively screening anti-Aids combined drug in large scale at once. The invention furthermore provides a plurality of high-efficiency low-toxicity anti-Aids three-drug or four-drug drug combinations which have huge clinic values for individually selecting treatment schemes for the patients resisting certain specific drugs.

Description

technical field [0001] The invention relates to a combination drug against HIV and a large-scale, one-time screening method thereof. Background technique [0002] Human acquired immunodeficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV). Now, AIDS has spread rapidly around the world. HIV is a virus that can attack the human immune system. It takes T lymphocytes in the human immune system as the main attack target, destroys T lymphocytes in large quantities, and makes the human body lose its immune function. Therefore, the human body is susceptible to various diseases, and malignant tumors can occur, with a high mortality rate. [0003] Over the past few years, numerous reports have demonstrated that combination therapy is superior to monotherapy. An outstanding example of this is the successful treatment of human immunodeficiency virus. The main problem in the field of combination drug therapy is that the type and dosage of drugs constitute a ve...

Claims

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Application Information

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IPC IPC(8): G06F19/24
CPCG16B40/00
Inventor 丁显廷何志明卢洪洲陈军
Owner SHANGHAI JIAO TONG UNIV
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