Intravenous Curcumin Formulation with Calcium Channel Blocker

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Solution Overview

Problem

Current methods for intravenous administration of curcumin face challenges such as low bioavailability due to insolubility and hepatic inactivation, leading to negligible therapeutic effects for systemic diseases, and curcumin induces hemolysis due to calcium ion imbalance, which is life-threatening at higher doses.

Innovation Solution

Formulating synthesized curcumin with a polylactic glycolic acid (PLGA) copolymer and liposomes, combined with calcium channel blockers, for intravenous administration at sub-hemolytic dosages to mitigate hemolysis and enhance bioavailability, allowing sustained release or continuous infusion to treat neoplastic and neurodegenerative diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If curcumin is administered intravenously to treat systemic diseases, then therapeutic efficacy is improved, but hemolysis occurs due to calcium ion imbalance

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidhemolysis

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

A calcium channel blocker is introduced as an intermediary substance that mediates between curcumin's therapeutic effects and its harmful hemolytic action. The calcium channel blocker binds to calcium channels in red blood cells, preventing calcium ion influx that would otherwise be triggered by curcumin, thereby eliminating hemolysis while preserving curcumin's therapeutic efficacy against cancer and neurodegenerative diseases

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If curcumin is administered orally to avoid toxicity, then safety is improved, but bioavailability becomes negligible due to insolubility and hepatic inactivation

Engineering Contradiction:

ImprovetoxicityVSAvoidbioavailability

Core Design Contradiction:

Object-affected harmful factorsVSQuantity of substance

Solution Approach 1:

The administration route and dosing parameters are changed from oral to intravenous to bypass first-pass hepatic inactivation and improve bioavailability. The intravenous route delivers curcumin directly to the bloodstream, avoiding gastrointestinal degradation and hepatic metabolism that limit oral bioavailability, while the calcium channel blocker prevents toxicity

Inventive Principle:

Principle #35Parameter changes

3Reliability

If higher doses of curcumin are administered to enhance therapeutic effect, then treatment efficacy is improved, but hemolysis becomes life-threatening

Engineering Contradiction:

Improvetreatment efficacyVSAvoidlife-threatening hemolysis

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The calcium channel blocker is administered concurrently with curcumin to preemptively counteract the harmful calcium ion influx that would lead to hemolysis. This preliminary anti-action prevents the harmful effect from occurring even at higher curcumin doses that would otherwise be life-threatening, allowing safe administration of effective therapeutic doses

Inventive Principle:

Principle #9Preliminary anti-action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach prevents curcumin-induced hemolysis and increases bioavailability, enabling effective treatment of systemic diseases like cancer and neurodegenerative disorders without the toxicity associated with higher doses, by controlling calcium ion influx and ensuring safe intravenous administration.

Implementation Method 1

one or more calcium channel blockers, wherein the composition mitigates a curcumin induced red blood cell (RBC) hemolysis

Methodology Applied

Scientific EffectCalcium channel blocking:

Implementation Method 2

the synthesized curcumin is enveloped by a polylactic glycolic acid (PLGA) copolymer, a layer of lipids to form a liposome

Methodology Applied

Scientific EffectEncapsulation:

Implementation Method 3

a layer of lipids to form a liposome

Methodology Applied

Scientific EffectLiposome formation:

Data Source

PatentUS8747890B2Intravenous infusion of curcumin and a calcium channel blocker

Publication Date: 2014.06.10 SIGNPATH PHARMA INC

AI summary

Compositions and methods for treating systemic diseases by intravenous administration of formulations of synthesized curcumin (diferuloylmethane) and concomitantly a calcium channel blocker to human subjects with neoplastic and neurodegenerative diseases are disclosed herein. The diseases are treated by prolonged administration of sub-optimal doses of liposomal curcumin or polymeric nanocurcumin or the sustained release curcumin from PLGA nanocurcumin at dosages below systemic hemolytic thresholds concomitantly with or without calcium channel blockers.