Aerosilization of stem cells or stem cell derivatives for pulmonary delivery
Inventors
Batchinsky, Andriy • ANTEBI, Ben • Beely, Brendan M. • Cancio, Leopoldo C. • Belson, Amir • Huss, Beverly • Hayes, Edward J. • Haydon, Jeff G.
Assignees
United States Department of the Army
Publication Number
US-11389400-B2
Publication Date
2022-07-19
Expiration Date
2037-01-27
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
A treatment system delivers a breathing gas and frozen stem cells or other biologic particles (FBP) to a bronchus of a lung of a patient in order to treat lung and other conditions. The breathing gas and the FBP are usually delivered through separate lumens. The FBP may be delivered concurrently with other frozen particles, such as frozen saline particles (FSP). The FBP/FSP will remain frozen at all times from preparation to delivery, and will thaw only after they are released into the lung.
Core Innovation
The invention relates to compositions, apparatus, methods for preparing, and delivering stem cells and other viable cells and cellular substances to humans and animals, specifically focusing on freezing stem cells and delivering frozen stem cells to a patient's lungs. It provides frozen cellular and biologic compositions, particularly stem cells, and methods for their preparation and delivery to treat lung conditions such as acute lung injury, ARDS, cystic fibrosis, emphysema, and COPD.
The problem addressed is the limitation in current stem cell delivery methods which include invasive local administration and systemic administration that may cause complications and poor viability. Existing inhalation delivery methods do not adequately preserve stem cell viability during micronization and delivery. There is a need for improved techniques that maintain viability of stem cells and biologics during preparation and pulmonary delivery, enhancing therapeutic efficacy.
The innovation involves delivering frozen biologic particles, primarily stem cells with an aqueous phase frozen, as flowable particles sized for deep lung delivery. These frozen particles remain frozen from preparation through delivery and thaw only after release into the lung, preserving viability and preventing necrosis or apoptosis. The invention employs low energy micronization to produce particles in an optimal size range (around 4 μm to 100 μm) suitable for inhalation and deep lung deposition carried by a breathing gas, typically delivered through specialized multi-lumen tubes with controlled dosing synchronized to patient inhalation.
Claims Coverage
The patent includes two independent method claims covering delivery of frozen biologic particles to patient lungs, and related system claims for controlled delivery of such particles.
Method for delivering frozen biologic particles entrained in breathing gas
Delivery of frozen biologic particles comprising a biologic material with a frozen aqueous phase formed into flowable particles sized 4 μm to 100 μm, entrained in a breathing gas stream to a bronchus, with the particles remaining frozen as solid ice during delivery and thawing after release into the lung.
Method for dispersing boluses of frozen biologic particles in carrier gas during inhalation
Dispersing multiple boluses of frozen biologic particles into a flowing carrier gas to produce an entrained stream delivered to the bronchus concurrently with a separate breathing gas stream synchronized with inhalation, with particles maintaining a frozen aqueous content during delivery.
Controlled delivery using multi-lumen breathing tubes and ventilators
Utilizing delivery of breathing gas and frozen biologic particles through separate or common lumens during inhalation cycles, with control over bolus size, inhalation rate, and venting of carrier gas to maintain target tidal volume and prevent premature thawing or lumen clogging.
Inclusion of frozen saline particles delivered concurrently
Simultaneous delivery of frozen saline particles with frozen biologic particles in the same or separate breathing gas streams to the bronchus, optionally through thermally insulated lumens.
Use of stem cells that remain viable after frozen delivery
Employing stem cells frozen with cryoprotectants that remain viable after delivery into the lung while still frozen, then thaw while being carried into the lower lung by respiration.
The independent claims cover methods and systems for delivering frozen biologic particles, including stem cells, in a frozen state entrained in breathing gas to deep lungs during inhalation, ensuring viability and controlled dosage. The claims encompass delivery apparatus, pulsed dosing synchronized with respiration, and simultaneous delivery of frozen saline particles.
Stated Advantages
Freezing prevents necrosis and apoptosis of stem cells during delivery, maintaining viability.
Low energy micronization reduces damage to stem cells compared to high energy ultrasonic methods.
Delivery of frozen particles allows protection of stem cells until reaching target lung tissues, enhancing localized administration and therapeutic potential.
Documented Applications
Local treatment of lung conditions including acute lung injury due to smoke inhalation, acute respiratory distress syndrome (ARDS), cystic fibrosis, emphysema, chronic occlusive pulmonary disease (COPD), and other pulmonary diseases or injuries.
Interested in licensing this patent?