Device and method for removal of blood-borne pathogens, toxins and inflammatory cytokines

• US 10,537,280 B2
• Filed: 08/13/2013
• Issued: 01/21/2020
• Est. Priority Date: 02/15/2011
• Status: Active Grant

• Current Assignee: ExThera Medical Corporation
• Original Assignee: ExThera Medical Corporation
• Inventors: McCrea, Keith, Ward, Robert S., Pitarra, Jr., George
• Primary Examiner(s): Kahelin, Michael W
• Assistant Examiner(s): Huh, Vynn V
• Application Number:
  US13/966,244
• Publication Number:
  US 20140012097A1
• Time in Patent Office: 2,352 Days
• Field of Search: 4352872, 604500, 600300
• CPC Class Codes: A61B 5/0002 Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network A61B5/07 takes precedence; transmission systems for measured values G08C; transmission H04B; transmission of digital information H04L; wireless communication networks H04W
• CPC Class Codes: A61B 5/01 Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue clinical contact thermometers G01K13/20
• CPC Class Codes: A61B 5/02028 Determining haemodynamic parameters not otherwise provided for, e.g. cardiac contractility or left ventricular ejection fraction
• CPC Class Codes: A61B 5/02055 Simultaneously evaluating both cardiovascular condition and temperature
• CPC Class Codes: A61B 5/0215 by means inserted into the body catheters A61M25/00
• CPC Class Codes: A61B 5/145 Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissuemeasuring of blood pressure or blood flow A61B5/02; non-radiation detecting or locating of foreign bodies in blood A61B5/06
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14542 for measuring blood gases A61B5/14551 takes precedence
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1468 using chemical or electrochemical methods, e.g. by polarographic means A61B5/1486 takes precedence
• CPC Class Codes: A61B 5/486 Bio-feedback A61B5/375 takes precedence
• CPC Class Codes: A61B 5/6866 Extracorporeal blood circuits, e.g. dialysis circuits
• CPC Class Codes: A61M 1/16 with membranes
• CPC Class Codes: A61M 1/34 Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
• CPC Class Codes: A61M 1/3673 Anticoagulant coating, e.g. Heparin coating
• CPC Class Codes: A61M 1/3679 by absorption A61M1/3675 takes precedence
• CPC Class Codes: A61M 2202/206 Viruses
• CPC Class Codes: A61M 2205/3303 Using a biosensor
• CPC Class Codes: A61M 2205/3331 Pressure; Flow
• CPC Class Codes: A61M 2205/3368 Temperature
• CPC Class Codes: B01J 20/321 : consisting of a polymer obtained by reactions involving only carbon to carbon unsaturated bonds
• CPC Class Codes: B01J 20/3212 : consisting of a polymer obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds
• CPC Class Codes: B01J 20/3251 : comprising at least two different types of heteroatoms selected from nitrogen, oxygen or sulphur

Abstract

The present invention is directed to an integrated system and a method for utilizing the system to detect and remove blood-borne factors of interest, such as pathogens and/or toxins and/or cytokines, from blood or serum (blood) by contacting the blood with a solid, essentially nonporous substrate which has been surface treated with molecules or chemical groups (the adsorbent media or media) having a binding affinity for the pathogens and/or toxins to be removed (the adsorbents). The invention can be used to remove virulence factors, e.g. toxins, that are released from various pathogens. In one aspect, the invention is for the treatment of sepsis and infection, such as infections associated with battle field trauma.

Claims

1. A system for broad-spectrum whole-blood extracorporeal separation of blood-borne factors of interest comprising:

an extracorporeal solid substrate or cartridge, wherein the solid substrate or cartridge is a broad-spectrum, anti-thrombogenic cartridge having a solid substrate, which is essentially nonporous, comprising covalently-bonded, end-point attached heparin on a high-surface-area polymer substrate;

one or more biosensors, wherein the one or more biosensors is an extracorporeal sensor for a nitric oxide biomarker; and

an extracorporeal pump for the extracorporeal circulation of blood, and a patient monitor, wherein the system extracorporeally separates blood-borne factors of interest from whole blood.

2. The system of claim 1 wherein the extracorporeal solid substrate is disposable.

3. The system of claim 1 further comprises at least one additional extracorporeal sensor selected from the group consisting of a blood pressure sensor, a temperature sensor, a pressure sensor, a blood glucose sensor, a blood gas sensor, or a sensor which detects nitric oxide (NO) metabolites, a sensor that detects cytokines, a sensor that detected bacteria or bacteria toxins, a sensor that detects viruses, a sensor that detects parasites, a sensor that detects fungi, a sensor that detects coagulation factors, a sensor that detects organ dysfunction proteins, a sensor that detects acute phase proteins, or a sensor that detects complement factors.

4. The system of claim 3, wherein the at least one additional extracorporeal sensor quantifies the amount of an additional biomarker in blood.

5. The system of claim 3, wherein the at least one additional extracorporeal sensor measures pressure readings, biosensor outputs, patient temperature, blood gas, or blood pressure.

6. The system of claim 5, comprising alarms correlated to cartridge pressure drop, biosensor output, patient data or system data.

7. The system of claim 1, wherein the one or more biosensors amperometrically detects blood-borne factors.

8. The system of claim 1, wherein the one or more biosensors chemometrically analyzes the presence and amount of blood-borne factors.

9. The system of claim 1, wherein the extracorporeal pump is a roller pump.

10. The system of claim 1 further comprising a extracorporeal power source.

11. An extracorporeal method for broad-spectrum whole-blood separation of blood-borne factors of a patient, comprising:

(a) detecting the presence or amount of a blood-borne factor of interest using an extracorporeal biosensor,

(b) bringing a sample of blood in contact using convection transport with a broad-spectrum, anti-thrombogenic extracorporeal cartridge having a solid substrate, which is essentially nonporous, comprising covalently-bonded, end-point attached heparin on a high-surface-area polymer substrate, and

(c) separating the sample from said broad-spectrum, anti-thrombogenic cartridge whereby said blood-borne factor is at least partially retained on said extracorporeal cartridge and the removed sample has a reduced amount of blood-borne factor.

12. The method of claim 11, wherein the extracorporeal biosensor detects an elevation in a biomarker.

13. The method of claim 11, wherein the extracorporeal biosensor detects levels of biomarkers in a patient at two or more time points.

14. The method of claim 11, wherein the extracorporeal biosensor continuously detects levels of biomarkers.

15. The method of claim 11, wherein the method further includes measuring a blood pressure of the patient using a blood pressure sensor.

16. The method of claim 11, where the blood-borne factors are separated without the prior identification of specific pathogens.

17. The method of claim 11, further comprising measuring pressure drop over the extracorporeal cartridge, extracorporeal biosensor output, or patient data.

18. The method of claim 17, further comprising alarming for caregiver feedback based on biosensor'"'"'s output.

19. The method of claim 17, wherein the method further comprising telemetry of measurements of patient data.

20. The method of claim 11, further comprising data logging, trending, and alarming for caregiver feedback, based on biosensor output.