Purified Crocetinic Acid Isolation for Pancreatic Cancer Potency

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Solution Overview

Problem

Pancreatic cancer lacks effective treatment options, with existing therapies being inadequate, leading to high mortality rates and a need for new anti-cancer agents.

Innovation Solution

Purification of crocetin from saffron to obtain a more potent compound, crocetinic acid, which is 50-times more effective than crude crocetin in inhibiting pancreatic cancer cell proliferation and inducing apoptosis, potentially combined with known anticancer agents like Gemcitabine and 5-FU.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If crude crocetin is used as an anti-cancer agent, then it shows some anti-tumor effect, but its potency is insufficient for effective treatment

Engineering Contradiction:
Improveanti-tumor efficacyVSAvoidpotency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent extracts and isolates crocetinic acid from crude crocetin through purification processes including chromatography. This separation removes impurities and concentrates the active anti-cancer component, transforming the weak crude extract into a potent purified compound with 50-times greater efficacy against pancreatic cancer cells.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the purity parameter of crocetin from crude (mixed composition) to purified (95%+ purity of crocetinic acid). This parameter change dramatically increases the anti-tumor potency while maintaining the biological activity, resolving the contradiction between reliability and productivity.

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If conventional treatments for pancreatic cancer are used, then standard therapy protocols are available, but treatment effectiveness is insufficient leading to high mortality

Engineering Contradiction:
Improveavailability of treatment protocolsVSAvoidtreatment effectiveness
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent introduces crocetinic acid as an intermediary substance that bridges the gap between conventional ineffective treatments and effective cancer therapy. This natural compound derived from saffron acts as a mediator that selectively targets pancreatic cancer cells through apoptosis induction, providing an effective treatment option where conventional therapies have failed.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If purified crocetin compounds are developed to increase potency, then anti-cancer effectiveness improves, but purification complexity and manufacturing difficulty increase

Engineering Contradiction:
Improveanti-cancer potencyVSAvoidpurification process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the crude crocetin mixture into individual components through chromatographic separation. By dividing the complex crude extract into discrete fractions and identifying crocetinic acid as the active component, the patent simplifies the purification strategy and enables targeted isolation of the potent anti-cancer compound.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentUS10155715B2Purified crocetin compound and method for treating, inhibiting, and/or prophylaxis of cancer, such as pancreatic cancer
Publication Date: 2018.12.18 VETERANS AFFAIRS U S DEPT OF
  • US10155715B2 patent drawing
  • US10155715B2 patent drawing
  • US10155715B2 patent drawing

AI summary

A fraction separated from crude crocetin by preparative HPLC, and identified using LC/MS and NMR as crocetinic acid, markedly regressed the proliferation and increased apoptosis in pancreatic cancer cells. Purified crocetinic acid showed more potency than 15 commercial or crude crocetin using proliferation and apoptosis as markers. Purified crocetinic acid also showed significant anti-tumorigenic activity against pancreatic cancer cells in a mouse model of pancreatic cancer. Given crocetinic acid's low toxicity, crocetinic acid could be used as a chemotherapeutic or chemopreventative agent for pancreatic cancer.