Herbal Extract Combination Therapy for Checkpoint Inhibitor GI Toxicity

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Solution Overview

Problem

Existing immune checkpoint inhibitors like pembrolizumab, nivolumab, and durvalumab cause significant gastrointestinal side effects such as nausea, diarrhea, fatigue, and colitis, limiting their therapeutic efficacy in treating tumors.

Innovation Solution

Combining herbal extracts from Scutellaria baicalensis, Glycyrrhiza uralensis, Paeonia lactiflora, and Ziziphus jujuba with immune checkpoint inhibitors to minimize side effects while maintaining anti-tumor activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If immune checkpoint inhibitors are used to treat tumors, then anti-tumor activity is improved, but gastrointestinal side effects worsen

Engineering Contradiction:

Improveanti-tumor activityVSAvoidgastrointestinal side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces herbal extracts (PHY906, Scutellaria baicalensis, Glycyrrhiza uralensis, Paeonia lactiflora, Ziziphus jujuba) as intermediary substances that mediate between the immune checkpoint inhibitor and the gastrointestinal system. These herbal extracts act as protective agents that reduce gastrointestinal toxicity while preserving the anti-tumor efficacy of the checkpoint inhibitor, effectively serving as a buffer or shield against harmful side effects.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a composite therapeutic regimen by combining immune checkpoint inhibitors with traditional herbal medicines. This composite approach integrates modern biotechnology (monoclonal antibodies) with traditional pharmacology (herbal extracts), resulting in a synergistic treatment that enhances therapeutic index by simultaneously achieving anti-tumor activity and reducing gastrointestinal toxicity.

Inventive Principle:

Principle #40Composite materials

2Productivity

If the dose of immune checkpoint inhibitors is increased to enhance anti-tumor activity, then therapeutic efficacy is improved, but side effects worsen

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidside effects

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the therapeutic parameter composition by adding herbal extracts to the treatment regimen. This parameter change allows for optimization of the therapeutic index - the ratio of effective dose to toxic dose - by introducing substances that selectively protect against toxicity while maintaining or enhancing anti-tumor efficacy at the same or lower inhibitor doses.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20250352598A1Improved Therapeutic Index of Anti-Immune Checkpoint Inhibitors Using Combination Therapy Comprising A PHY906 Extract, A Scutellaria baicalensis Georgi (S) Extract or A Compound From Such Extracts

Publication Date: 2025.11.20 YALE UNIVERSITY

AI summary

The present invention provides a method of treating melanoma and other cancers in a subject, the method comprising administering to the subject in need thereof a therapeutically effective amount of an herbal extract of PHY906 or Scutellaria baicalensis, a fraction thereof or any active chemical present in the herbal extract or fraction thereof, and one or more immune checkpoint inhibitors. In certain embodiments, the method further comprises administering at least one herbal extract, a fraction thereof or any active chemical present in the herbal extract or fraction thereof, of at least one herb selected from the group consisting of Glycyrrhiza uralensis, Paeonia lactiflora, and Ziziphus jujuba. The methods of the invention are useful for treating cancer such as melanoma, non-small cell lung cancer, renal cell carcinoma, liver cancer, colon cancer, urothelial bladder cancer and pancreatic cancer. In certain embodiments, administration of the herbal extracts of the invention counteract one or more gastrointestinal side effects of the immune checkpoint inhibitors and/or increase their therapeutic index against cancer.