Ultrafine Bubble Compositions for Pharmaceutical Delivery and Fermentation

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Solution Overview

Problem

Current aqueous compositions with ultrafine bubbles, primarily formed through vaporous or 'hard' cavitation, have limitations in stability, solubility, and bioavailability of solutes, and there is a need for improved methods in fermentation processes for oxygen transfer and biomass production.

Innovation Solution

The development of aqueous compositions that incorporate ultrafine bubbles produced via gaseous or 'soft' cavitation, combined with a non-gaseous solute, to enhance bioavailability, solubility, and stability, along with the use of microbubble generators to improve oxygen transfer in fermentation processes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If ultrafine bubbles are formed through vaporous or 'hard' cavitation, then bubbles are created with water molecules surrounding exogenously provided gases, but the compositions have substantially different structural, functional, and stability characteristics that result in reduced stability, solubility, and bioavailability of solutes

Engineering Contradiction:

Improveultrafine bubble concentrationVSAvoidstability of solutes

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent changes the cavitation mode parameter from vaporous/hard cavitation to gaseous/soft cavitation. This parameter change fundamentally alters the bubble formation mechanism, resulting in bubbles with water molecules surrounding gases released from solution rather than exogenously provided gases, thereby improving solute stability, solubility, and bioavailability

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent utilizes the phase transition of dissolved gases from aqueous phase to gaseous phase within bubbles during gaseous cavitation. This phase transition of endogenous gases creates a more stable environment for solutes compared to introducing external gases through hard cavitation, resolving the contradiction between bubble quantity and solute stability

Inventive Principle:

Principle #36Phase transitions

2Use of energy by moving object

If traditional sparging is used to deliver oxygen in bioreactor systems, then oxygen is bubbled through the culture medium, but mass transfer limitations, bubble coalescence, and shear stress on cells occur due to high gas flow rates

Engineering Contradiction:

Improveoxygen transfer efficiencyVSAvoidshear stress on cells

Core Design Contradiction:

Use of energy by moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent changes the bubble size parameter from conventional large bubbles to ultrafine bubbles, and the cavitation mode from hard to soft cavitation. These parameter changes enable efficient oxygen transfer without requiring high gas flow rates, thereby eliminating shear stress on cells while maintaining or improving oxygen transfer efficiency

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent replaces the mechanical sparging system with a gaseous cavitation system. Instead of mechanically bubbling gas through the medium at high flow rates, the system uses cavitation-induced phase transition of dissolved gases to create ultrafine bubbles, achieving oxygen transfer without the harmful mechanical shear stress

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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

The compositions with ultrafine bubbles formed by 'soft' cavitation demonstrate improved bioavailability, solubility, and stability of solutes, while the enhanced oxygen transfer in fermentation processes leads to increased biomass production and yield of biological compounds.

Implementation Method 1

gaseous cavitation occurs when gases dissolved within a liquid fall out of solution with decreasing pressure, typically at pressures higher than the vapor pressure of the liquid itself-creating bubbles formed from particles or molecules of the liquid and the released gases

Methodology Applied

Scientific EffectGaseous cavitation: Cavitation

Implementation Method 2

The availability of oxygen can be a limiting factor in achieving optimal cell densities and production rates. Efficient oxygen transfer is essential to support the metabolic needs of cells

Methodology Applied

Scientific EffectGas absorption: Absorption (physical)

Implementation Method 3

the organization of water molecules influences the stability, solubility, and bioavailability of any solutes dissolved within

Methodology Applied

Scientific EffectSolvation: Solvation

Data Source

PatentUS20250161228A1Compositions comprising ultrafine bubbles and methods of using thereof in a method of producing and delivering active pharmaceutical ingredients and other dissolved solutes

Publication Date: 2025.05.22 HYDROSOME IP LLC

AI summary

The disclosure provides compositions including ultrafine bubbles having water and gases released from solution in the water. The compositions may dissolve, surround, and/or stabilize one or more non-gaseous solutes. Methods of making and using the compositions for delivering an active pharmaceutical ingredient to cells are also provided. The methods of making the compositions including ultrafine bubbles include processes for dissolving, surrounding, and/or stabilizing non-gaseous solutes and/or active pharmaceutical ingredients with ultrafine bubbles. Methods of using the compositions to produce active pharmaceutical ingredients and/or increase yield thereof via fermentation are also provided.