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Publication Number
US-12076474-B2
Publication Date
2024-09-03
Expiration Date
Abstract
The present invention concerns methods of treating a patient suffering from a traumatic brain injury (TBI), comprising contacting said patient's blood with a sorbent for an inflammatory mediator and kits for performing such treatments.
Core Innovation
The invention relates to treating traumatic brain injury by contacting a patient’s blood with a sorbent for an inflammatory mediator. The sorbent includes a biocompatible polymer configured to remove inflammatory mediators and DAMP-associated cytokines, including alarmins such as HMGB1 and other cytokines and inflammatory markers. The approach is directed to blood contacting in the context of traumatic brain injury, using the sorbent to reduce inflammatory mediator burden associated with the injury.
The biocompatible polymer is defined by a pore structure with total pore volume in a specified range from 50 Å to 3000 Å. Additional constraints relate pore-volume ratios across pore-size ranges, including a ratio smaller than 200:1 for pore sizes from 50 Å to 3000 Å compared to pore sizes from 500 Å to 3000 Å, and a ratio greater than 20:1 for pore sizes from 50 Å to 3000 Å compared to pore sizes from 1000 Å to 3000 Å. These pore-volume and ratio constraints define the sorbent’s polymer pore characteristics for inflammatory mediator removal.
The disclosure includes embodiments where blood contacting is implemented using cartridge-based extracorporeal blood circulation and kit formats. The sorbent can be contained within a cartridge, with removal and returning of blood performed as part of a continuous circuit connecting an artery and a vein in the patient. The polymer constructions described include various porous, coated, or functionalized biocompatible polymers and related configurations, aligned to the defined pore-structure constraints.
Claims Coverage
The document provides one independent claim and dependent claim refinements focused on the biocompatible polymer pore-volume constraints and implementation of the blood-contacting sorbent as an external extracorporeal cartridge circuit and related formats. The inventive features explicitly include inflammatory mediator sorption using a polymer with specified pore-volume and pore-volume ratio relationships over defined pore-size ranges, together with dependent refinements on polymer identity and contacting containment and circuit implementation.
Treating traumatic brain injury by blood contact with inflammatory mediator sorbent
A method of treating a patient suffering from a traumatic brain injury (TBI) by contacting the patient’s blood with a sorbent for an inflammatory mediator.
Biocompatible polymer sorbent with pore-volume in specified pore-size range
The sorbent comprises a biocompatible polymer having a pore structure such that the total pore volume of pore size in the range of 50 Å to 3000 Å is from about 0.5 cc/g to 3.0 cc/g dry polymer.
Pore-volume ratio constraints across pore-size ranges
The ratio of pore volume between 50 Å to 3,000 Å in diameter to pore volume between 500 Å to 3,000 Å in diameter is smaller than 200:1, and the ratio of pore volume between 50 Å to 3,000 Å in diameter to pore volume between 1,000 Å to 3,000 Å in diameter is greater than 20:1.
Across the independent method claim, the core inventive coverage is the use of a sorbent containing a biocompatible polymer to treat traumatic brain injury by contacting patient blood for inflammatory mediator removal, with strict pore-structure total pore volume and pore-volume ratio constraints across defined pore-size ranges.
Stated Advantages
Improved survival in the described traumatic brain injury model.
Reduced inflammatory mediator/cytokine levels in the described traumatic brain injury model.
Documented Applications
Treating a patient suffering from traumatic brain injury (TBI) by contacting the patient’s blood with a sorbent for inflammatory mediator removal, including embodiments using cartridge-based extracorporeal blood circulation and a continuous artery-to-vein circuit.
Rat closed cortical impact (CCI) traumatic brain injury model combined with hemorrhagic shock/resuscitation, with treatment using porous polymer beads in an artery-to-vein cartridge to assess survival and inflammatory mediator/cytokine reduction.
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