Combination Therapy Reduces Renal Toxicity and Metabolic Disorders

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Solution Overview

Problem

Drug-induced nephrotoxicity, dyslipidemia, and hyperglycemia pose significant challenges, particularly with medications like Cyclosporine A, Cisplatin, and Gentamicin, which cause renal toxicity and metabolic disorders as side effects, and existing treatments are inadequate in effectively mitigating these issues.

Innovation Solution

A combination therapy involving a peroxisome proliferator-activated receptor alpha (PPARA) activator and/or a glucose transporter 2 (GLUT2) inhibitor, often in conjunction with a sodium-glucose linked transporter type 2 (SGLT2) inhibitor, is administered to reduce renal tissue toxicity, dyslipidemia, and hyperglycemia by targeting specific cellular pathways.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If nephrotoxic drugs (Cyclosporine A, Cisplatin, Gentamicin) are administered to treat diseases, then therapeutic efficacy is improved, but renal tissue toxicity increases

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidrenal tissue toxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary anti-action by administering protective agents (PPARA activators, SGLT2 inhibitors, GLUT2 inhibitors) before or concurrently with nephrotoxic drugs to prevent renal damage. These agents activate protective cellular pathways in advance, reducing oxidative stress, lipid accumulation, and apoptosis that would otherwise be caused by the nephrotoxic drugs, thereby allowing full therapeutic dosing without increased toxicity.

Inventive Principle:

Principle #9Preliminary anti-action

Solution Approach 2:

The patent uses protective agents as intermediaries between the nephrotoxic drugs and renal tissue. These intermediaries (PPARA activators, SGLT2 inhibitors, GLUT2 inhibitors) block the harmful transmission of toxic effects from the drugs to the kidney cells while allowing the drugs to maintain their therapeutic action on the target disease.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If nephrotoxic drugs are administered to treat diseases, then therapeutic efficacy is improved, but metabolic disorders (dyslipidemia andhyperglycemia) increase

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidmetabolic disorders

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful metabolic side effects into beneficial effects by using the same drug classes that cause the problems therapeutically to solve them. For example, SGLT2 inhibitors are used to treat hyperglycemia that was caused by nephrotoxic drugs, and PPARA activators are used to treat dyslipidemia, thereby converting the harmful metabolic disruptions into therapeutic opportunities.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent changes metabolic parameters by administering agents that specifically target and correct the metabolic disruptions caused by nephrotoxic drugs. PPARA activators alter lipid metabolism parameters to reduce dyslipidemia, while SGLT2 inhibitors and GLUT2 inhibitors change glucose metabolism parameters to correcthyperglycemia, thereby restoring metabolic homeostasis.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20230201226A1Combination therapy for reducing drug-induced nephrotoxicity, dyslipidemia and hyperglycemia

Publication Date: 2023.06.29 YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD

AI summary

Methods, compositions and kits for reducing renal tissue toxicity in a subject caused by a kidney damaging agent are provided. The methods comprise administering to the subject: (i) a kidney damaging agent; (ii) a PPARA activator; and (iii) an inhibitor of a cellular pathway selected from the group consisting of C/EBP, PPARG, ER stress, GLUT2 and SGLT1/2; or (i) a kidney damaging agent; (ii) a SGLT2 inhibitor; and (iii) a PPARA activator, a C/EBP inhibitor, a PPARG inhibitor, or an ER stress inhibitor.