Dissolved Oxide Compositions With pH-Triggered Bioactive Delivery
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Solution Overview
Problem
Hydrophobic bioactive molecules exhibit poor bioavailability and pharmacokinetics, necessitating improved formulations to enhance their absorption and distribution in biological systems.
Innovation Solution
Development of anionic compounds dissolved in water-miscible liquids that convert into hydrophobic molecules at neutral pH, allowing rapid partitioning and adherence to epithelial surfaces for enhanced absorption, thereby avoiding first-pass metabolism.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If hydrophobic bioactive molecules are administered in conventional formulations, then the molecules can be delivered to the target site, but bioavailability and pharmacokinetics are poor due to limited absorption
Solution Approach 1:
The patent changes the chemical parameter of the bioactive molecule by converting it from a neutral hydrophobic form to an anionic form that is soluble in water-miscible liquids. This parameter change enables the molecule to be administered in aqueous formulations while maintaining the ability to convert back to its active hydrophobic form at the target site, thereby improving bioavailability and absorption rate
Solution Approach 2:
The patent uses water-miscible liquids as an intermediary medium that temporarily solubilizes the anionic form of the bioactive molecule. This intermediary allows the molecule to be transported in the aqueous environment of the body before converting to its active form at the target site, overcoming the limitation of poor solubility of hydrophobic molecules
2Reliability
If hydrophobic molecules are used, then the molecules can cross lipid membranes, but they exhibit poor solubility in water-miscible liquids and bodily fluids
Solution Approach 1:
The patent applies dynamics by creating a reversible transformation between two forms of the molecule: an anionic form that is soluble in water-miscible liquids for transport, and a neutral hydrophobic form that can cross lipid membranes. The molecule dynamically switches between these forms based on the environmental conditions (pH), allowing it to optimize its properties for different physiological barriers
Solution Approach 2:
The patent changes the charge parameter of the molecule from neutral to anionic, which fundamentally alters its solubility characteristics. This parameter change enables the molecule to be solubilized in water-miscible liquids while maintaining the ability to cross lipid membranes when converted back to its neutral form at the target site
3Reliability
If conventional formulations are used, then the molecules can be administered, but first-pass metabolism reduces bioavailability
Solution Approach 1:
The patent applies preliminary action by converting the bioactive molecule to its anionic form before administration, which prevents first-pass metabolism from acting on the neutral hydrophobic form. The anionic form is more resistant to metabolic degradation in the liver, and only converts to the active neutral form after passing through the first-pass metabolism barrier, thereby reducing metabolic loss and improving bioavailability
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
Improves bioavailability and pharmacokinetics by facilitating rapid absorption through epithelial tissues, enhancing the delivery of hydrophobic molecules into the bloodstream or skin.
Implementation Method 1
The administration of anions that are dissolved in a water-miscible liquid to an organism results in the pH-dependent conversion of the anions into hydrophobic molecules
Implementation Method 2
The molecules then rapidly partition out of the water-miscible liquid and adhere to the epithelium where they absorb into the blood
Data Source
AI summary
Various aspects of this patent document relate to compositions that comprise an anion that is the conjugate base of a hydrophobic molecule that has a pKa, for example, of at least 7 and no greater than 12. These compositions display improved properties when formulated to interact with an organism because the anions carry negative charges that allows them to both dissolve in water-miscible liquids and maximize their surface area. Interaction with an organism results in at least partial conversion of the anion into the hydrophobic molecule after which the hydrophobic molecule partitions out of a water-miscible liquid and into the organism.