Purified crocetin compound and method for treating, inhibiting, and/or prophylaxis of cancer, such as pancreatic cancer
Inventors
Dhar, Animesh • Gutheil, William G.
Assignees
University of Kansas • US Department of Veterans Affairs • University of Missouri Columbia
Publication Number
US-10155715-B2
Publication Date
2018-12-18
Expiration Date
2031-10-07
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Abstract
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.
Core Innovation
The invention relates to a purified crocetin compound, identified as crocetinic acid, which is separated from crude crocetin by preparative high-performance liquid chromatography (HPLC) and characterized by LC/MS and nuclear magnetic resonance (NMR). This purified crocetinic acid shows markedly increased potency in regressing proliferation and increasing apoptosis of pancreatic cancer cells compared to crude or commercial crocetin. The purified compound demonstrated significant anti-tumorigenic effects in both in vitro models and mouse models of pancreatic cancer.
The problem addressed is the lack of effective conventional treatments for pancreatic cancer, which is a highly lethal malignancy with poor survival rates. Existing treatments fail to cure or adequately treat pancreatic cancer patients, creating a pressing need for new therapeutic agents with high efficacy and low toxicity. The invention seeks to develop novel therapeutic strategies by isolating and purifying crocetinic acid to obtain a compound with substantially greater potency and low toxicity as a chemotherapeutic or chemopreventative agent for pancreatic cancer.
The invention also proposes that purified crocetinic acid may be used alone or in combination with known anticancer agents such as Gemcitabine and 5-fluorouracil (5-FU) to form novel combination therapies. The purified compound is about 50 times more potent than crude crocetin in inhibiting proliferation and stimulating apoptosis, and it acts by mechanisms including inhibition of histone deacetylase, EGFR signaling pathways, and modulation of pro-apoptotic and anti-apoptotic proteins. These findings provide a foundation for future clinical trials and development of effective treatments targeting pancreatic cancer.
Claims Coverage
The patent includes one independent claim covering a method for treating or inhibiting cancer involving administration of purified crocetinic acid along with gemcitabine and 5-fluorouracil. The claim encompasses specific treatment parameters and preparations of the purified compound.
Method of treating or inhibiting cancer using purified crocetinic acid combined with gemcitabine and 5-fluorouracil
The method consists of administering an effective amount of a purified crocetinic acid compound together with gemcitabine and 5-fluorouracil (5-FU) to a subject in need thereof.
Use of purified crocetinic acid to treat pancreatic cancer
The cancer treated includes pancreatic cancer, specifying the application of the method to this particular cancer type.
Administration routes of the crocetinic acid compound
The purified crocetinic acid compound may be administered orally or intravenously.
Applicable subjects for treatment
The treated subject may be a human or an animal, expanding applicability.
Potency and dosing compared to crude crocetin
The effective amount of purified crocetinic acid used is less than the amount of crude crocetin needed to achieve the same effect, with at least a 50-fold reduction in required dosage.
Characterization of purified crocetinic acid
The purified compound has a specific HPLC spectrum as shown in the patent's FIG. 2A left panel, confirming its identity.
Method of purification from crude crocetin
Purified crocetinic acid compound is obtained by alkaline treatment (0.01 mM sodium hydroxide) of crude crocetin followed by purification using HPLC and LC/MS.
The claims provide coverage for a method of treating cancer, particularly pancreatic cancer, using a purified and characterized crocetinic acid compound administered with standard chemotherapy agents, with distinct dosing advantages, routes, and methods of preparing the potent purified compound.
Stated Advantages
Purified crocetinic acid is about 50 times more potent than crude crocetin in inhibiting cancer cell proliferation and inducing apoptosis.
The compound exhibits low toxicity, making it a suitable chemotherapeutic or chemopreventative agent.
Purified crocetinic acid effectively inhibits key molecular pathways involved in pancreatic cancer, including histone deacetylase activity, EGFR signaling, and modulates apoptosis regulators.
The invention provides a basis for developing combination therapies with known anticancer drugs, potentially enhancing efficacy and reducing toxicity.
Documented Applications
Treatment, inhibition, and prevention of pancreatic cancer using purified crocetinic acid.
Use of purified crocetinic acid as a chemotherapeutic or chemopreventative agent against cancer.
Combination therapy of purified crocetinic acid with known anticancer agents such as gemcitabine and 5-fluorouracil for pancreatic cancer.
Pharmaceutical formulations comprising purified crocetinic acid for therapeutic use.
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