Apparatus and method for down-regulating immune system mediators in blood

• US 7,207,964 B2
• Filed: 03/17/2003
• Issued: 04/24/2007
• Est. Priority Date: 03/17/2003
• Status: Expired due to Fees

• Current Assignee: Hemavation LLC
• Original Assignee: Hemavation LLC
• Inventors: Walker, Kimberly A., Davidner, Alan A., Mallett, Scott R.
• Primary Examiner(s): Bianco; Patricia
• Application Number:
  US10/390,558
• Publication Number:
  US 20040186410A1
• Time in Patent Office: 1,499 Days
• Field of Search: 604/4.01, 604/6.01, 604/6.1, 604 501- 504, 604/6.04, 604/6.05, 604 607- 609, 604 613- 616, 604/19, 604/28, 604/29, 604/500, 604506- 7, 604/113, 604/114, 422 44- 48, 210/645, 210/650, 210/651, 210/663, 210660-661, 210/787, 210/741, 210/748, 210/767, 210/774, 210805- 6
• US Class Current: 604/6.08
• CPC Class Codes: A61L 2/0011 using physical methods
• CPC Class Codes: A61M 1/3431 upstream of the filter
• CPC Class Codes: A61M 1/3468 using treated filtrate as substitution fluid
• CPC Class Codes: A61M 1/3472 with treatment of the filtrate
• CPC Class Codes: A61M 1/3482 by filtrating the filtrate using another cross-flow filter, e.g. a membrane filter
• CPC Class Codes: A61M 1/3623 Means for actively controlling temperature of blood
• CPC Class Codes: A61M 1/3681 by irradiation
• CPC Class Codes: A61M 1/3683 using photoactive agents
• CPC Class Codes: A61M 2205/053 ultraviolet
• CPC Class Codes: A61M 2205/75 with filters
• CPC Class Codes: A61M 2230/207 hematocrit

Abstract

A method and apparatus for preventing and treating septicemia in patient blood is provided. The extracorporeal system includes an antimicrobial device to inactivate at least 99% of bloodborne microorganisms, a hemoconcentrator/filtration unit to remove approximately 50–75% of target molecules from the patient blood and a filter unit to remove target molecules from patient blood from the sieved plasma filtrate. Target molecules are produced by microorganisms, as well as by the patient'"'"'s cells. These molecules include endotoxins from Gram negative bacteria, exotoxins from Gram negative and Gram positive bacteria, as well as RAP protein mediator from Staphylococcus aureus, and cell mediators such as tumor necrosis factor-alpha, and interleukin 1-beta, interleukin 6, complement proteins C3a and C5a, and bradykinin.

Claims

1. A method for down-regulating a patient'"'"'s immune system by removing one or more immune system mediators from the patient'"'"'s blood, comprising:

removing at least a portion of the patient'"'"'s blood;

diluting the blood with a diluent to provide diluted blood, thereby reducing the hematocrit of said blood;

concentrating the diluted blood using a membrane having a transmembrane pressure greater than 76 mmHg, thereby removing the diluent therefrom;

filtering said diluted blood to remove one or more immune system mediators from said diluted blood, thereby producing treated blood; and

returning the treated blood to the patient.

2. The method of claim 1, wherein the step of filtering said diluted blood to remove one or more immune system mediators comprises removing an inflammatory mediator.

3. The method of claim 2, wherein the step of removing an inflammatory mediator comprises reducing the concentration of at least one inflammatory mediator by about 75% in less than about 4 hours.

4. The method of claim 2, wherein the step of removing the inflammatory mediator comprises removing a inflammatory mediator selected from the group consisting of one or more of the following:

TNF-α

, IL-1β

, IL-6, IL-8, IL-10, IL-12, LPB, IFNγ

, LIF, MIF, MCP-1, C3-a, C5-a, exotoxins and endotoxins.

5. The method of claim 4, further comprising reducing the concentration of TNF-α

by about 50% in less than about 4 hours.

6. The method of claim 1, wherein the step of filtering said diluted blood comprises filtering said diluted blood using at least two filters.

7. The method of claim 6, wherein the step of filtering said diluted blood comprises filtering said diluted blood using a first filter having a porosity of about 70 kilodaltons to about 90 kilodaltons.

8. The method of claim 6, wherein the step of filtering said diluted blood comprises filtering said diluted blood using a second filter having a porosity of about 10 kilodaltons to about 30 kilodaltons.

9. The method of claim 6, wherein the step of filtering said diluted blood comprises filtering said diluted blood using two cytokine filters, each cytokine filter having a porosity of about 10–

30 kilodaltons.

10. The method of claim 1, wherein said concentrating step and said filtering step occur substantially simultaneously.

11. The method of claim 1, further comprising returning the diluent removed from the blood to a diluent source via a recycle path.

12. The method of claim 11, further comprising returning the diluent removed from the blood to a diluent source via a recycle path using a recycle path filter.

13. The method of claim 12, further comprising using recycle path filter comprised of electrostatically charged, melt-blown material.

14. The method of claim 1, further comprising oxygenating the blood received from the patient.

15. The system of claim 1, further comprising heating at least a portion of the blood to about body temperature.

16. The system of claim 1, further comprising cooling at least a portion of the blood to about body temperature.

17. The system of claim 1, further comprising heating at least a portion of the blood to between about 34°

C. to about 42°

C.

18. The system of claim 1, further comprising cooling at least a portion of the blood to between about 34°

C. to about 42°

C.

19. The system of claim 1, further comprising changing the temperature of at least a portion of the blood by about 1°

C.to about 10°

C.

20. The method of claim 1, further comprising providing at least one pump for moving said blood or diluent.

21. The method of claim 1, further comprising transporting said diluted blood at a flow rate of less than 400 ml/min.

22. The method of claim 1, further comprising irradiating at least a portion of the diluted blood.

23. The method of claim 22, wherein the step of irradiating at least a portion of the diluted blood comprises:

receiving blood from the patient;

supplying a portion of the received blood to an irradiation device; and

returning the remainder of the received blood to the patient.

24. The method of claim 22, wherein the step of irradiating at least a portion of the diluted blood comprises:

providing a UV light source;

providing a fluid chamber adjacent to said UV light source, said fluid chamber confining the diluted blood to a thin film for exposure to said UV light source; and

irradiating at least a portion of the diluted blood with said UV light source.

25. The method of claim 22, wherein the step of irradiating at least a portion of the diluted blood comprises delivering ultraviolet radiation to the diluted blood in a dose ranging from about 2 mW/cm² to about 20 mW/cm².

26. The method of claim 22, wherein the step of irradiating at least a portion of the diluted blood comprises delivering a dose of ultraviolet radiation to the diluted blood sufficient to deliver an effective dose of about 1 mW/cm² to about 19 mW/cm² to said diluted blood.

27. The system of claim 24, wherein the step of providing a fluid chamber comprises providing a bag to contain the diluted blood, said bag having a length in the range of about 15 inches to about 20 inches, a width in the range of about 8 inches to about 10 inches, and a fluid path having a width of about 0.75 inches to about 1 inch.

28. The method of claim 24, further comprising transporting at least a portion of the diluted blood through a serpentine path during irradiation.

29. The method of claim 1, wherein the step of concentrating the diluted blood comprises providing two hemoconcentrators connected in series.

30. The method of claim 1, wherein the step of concentrating the diluted blood comprises:

providing a hollow cylinder; and

providing a central core formed of hollow fibers axially disposed within said hollow cylinder.

31. The system of claim 30, wherein the step of providing a hollow cylinder comprises providing a hollow cylinder having a length of about 10 inches and a diameter of about 1.5 inches.

32. The system of claim 30, wherein the step of providing a central core comprises providing a central core having a surface area in the range of between about 1.2 m2 to about 2.4 m2.

33. The method of claim 1, wherein returning the blood to the patient further comprises providing tubing for the return path.

34. The method of claim 1, further comprising providing a reservoir connected to receive material filtered from the blood.

35. The method of claim 1, further comprising providing an inlet pressure sensor for monitoring the pressure of the blood.

36. The method of claim 1, wherein the step of diluting the blood comprises reducing the hematocrit to about 5% to about 20%.

37. The method of claim 1, wherein the step of concentrating the diluted blood using a membrane having a transmembrane pressure greater than 76 mmHg comprises using a membrane having a transmembrane pressure having a range of about 80 mmHg to about 85 mmHg.

38. The method of claim 1, wherein the step of concentrating the diluted blood using a membrane having a transmembrane pressure greater than 76 mmHg comprises using a membrane having a transmembrane pressure having a range of about 86 mmHg to about 95 mmHg.

39. The method of claim 1, wherein the step of concentrating the diluted blood using a membrane having a transmembrane pressure greater than 76 mmHg comprises using a membrane having a transmembrane pressure having a range of about 96 mmHg to about 105 mmHg.

40. The method of claim 1, wherein the step of concentrating the diluted blood using a membrane having a transmembrane pressure greater than 76 mmHg comprises using a membrane having a transmembrane pressure greater than about 105 mmHg.

41. The method of claim 1, wherein removing at least a portion of the patient'"'"'s blood comprises providing blood from a patient having an inflammatory disease.

42. The method of claim 41, further comprising providing blood from a patient having an inflammatory disease, wherein said inflammatory disease is selected from the group consisting of:

sepsis, acute renal failure, ischemic stroke, Sudeck'"'"'s syndrome, chronic fatigue syndrome, heat stroke, Hodgkin'"'"'s Disease, lupus, myocardial infarction, AIDS, viremia, HCV, HBV, tuberculosis, muscular dystrophy or multiple sclerosis, Acute Respiratory Distress Syndrome, and heart disease.

43. The method of claim 1, further comprising reducing free radicals in a patient'"'"'s blood, comprising:

exposing a first portion of the patient'"'"'s blood to ultraviolet light; and

exposing a second portion of the patient'"'"'s blood to one or more free radical quenchers in a dose sufficient to reduce free radicals in said first portion of the patient'"'"'s blood.

44. The method of claim 1, wherein the step of exposing a second portion of the patient'"'"'s blood to one or more free radical quenchers comprises exposing said second portion of the patient'"'"'s blood to one or more free radical quenchers selected from the group consisting of one or more of the following:

Zn, Cu, manganese, selenium, vitamin A, C, B, B complex, K, P, lycopene, superoxide dismutase, co-enzyme Q10, catechins, polyphenols, flavanols,depsides, quinic acids, carotenoids, thearubigens, theaflavin, theaflavic acids and ethyl pyruvate.

45. The method of claim 1, further comprising administering vitamin therapy to a patient'"'"'s blood, comprising:

exposing a portion of the patient'"'"'s blood to one or more vitamins in a dose sufficient to reduce one or more toxins in said portion of the patient'"'"'s blood.

46. The method of claim 45, wherein the step of exposing a portion of the patient'"'"'s blood to one or more vitamins comprises exposing a portion of the patient'"'"'s blood to one or more antioxidants.

47. A system for down-regulating a patient'"'"'s immune system by removing one or more immune system mediators from the patient'"'"'s blood, comprising:

apparatus for removing blood from the patient;

a diluent source for supplying a diluent to the blood which has been removed from the patient for the purpose of diluting the blood and reducing the hematocrit thereof;

a first filter for receiving the diluted blood and extracting one or more immune system mediators and diluent therefrom, said first filter having a transmembrane pressure greater than 76 mmHg;

a second filter for receiving the output from said first filter including immune system mediators and diluent and extracting the immune system mediators therefrom; and

a return pathway for returning a portion of the blood to the patient after the immune system mediators and diluent have been extracted therefrom by said first filter.

48. The system of claim 47, further comprising an irradiation means for irradiating the diluted blood in order to inactivate one or more toxins in the diluted blood.

49. The system of claim 48, wherein said irradiation means comprises:

a UV light source; and

a fluid chamber adjacent to said UV light source, said fluid chamber confining said fluid to a thin film for exposure to said UV light source.