Device, system, and method for controllably reducing inflammatory mediators in a subject

• US 20100216226A1
• Filed: 02/25/2009
• Published: 08/26/2010
• Est. Priority Date: 02/25/2009
• Status: Active Grant

• Current Assignee: Gearbox LLC (Intellectual Ventures LLC)
• Original Assignee: Searete LLC (Intellectual Ventures LLC)
• Inventors: Ishikawa, Muriel Y., Myhrvold, Nathan P., Langer, Robert, Jung, Edward K.Y., Wood, Lowell L. JR., Hyde, Roderick A., Sweeney, Elizabeth A., Leuthardt, Eric C.
• Granted Patent: US 8,454,547 B2
• Time in Patent Office: Days
• US Class Current: 435/287.200
• CPC Class Codes: A61B 18/042 using additional gas becoming plasma
• CPC Class Codes: A61B 18/1815 using microwaves
• CPC Class Codes: A61B 2018/1861 with an instrument inserted into a body lumen or cavity, e.g. a catheter
• CPC Class Codes: A61M 1/30 Single needle dialysis ; Reciprocating systems, alternately withdrawing blood from and returning it to the patient, e.g. single-lumen-needle dialysis or single needle systems for hemofiltration or pheresis
• CPC Class Codes: A61M 1/3679 by absorption A61M1/3675 takes precedence
• CPC Class Codes: A61M 1/3681 by irradiation
• CPC Class Codes: A61M 1/3683 using photoactive agents
• CPC Class Codes: A61M 1/3687 Chemical treatment A61M1/3675 takes precedence
• CPC Class Codes: A61M 1/3689 by biological cells
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: A61N 2007/0039 using microbubbles
• CPC Class Codes: A61N 5/02 using microwaves
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent
• CPC Class Codes: A61N 7/02 Localised ultrasound hyperthermia hyperthermia in general A61F7/00

Abstract

Devices, systems, and methods are provided for controlling an inflammatory response in a subject. Devices, systems, and methods are provided that alter the functional structure of one or more inflammatory mediators in the peripheral blood of the subject. The device or system is useful in a method for treating an inflammatory disease or condition in the subject.

Claims

1. A device comprising:

a sensor configured to detect one or more inflammatory mediators in peripheral blood of a subject;

a controller in communication with the sensor, and a means for modulating a physiological effect of the one or more inflammatory mediators responsive to the controller, the controller configured to adjust the modulating means to achieve a target value of the detected one or more inflammatory mediators in the peripheral blood of the subject.

2. The device of claim 1, wherein the means for modulating a physiological effect of the one or more inflammatory mediators include a treatment chamber configured to receive at least a portion of the peripheral blood through a flow route, the controller configured to control flow of peripheral blood through the flow route into the treatment chamber, and the treatment chamber including one or more reactive components configured to alter a functional structure of the one or more inflammatory mediators in the peripheral blood.

3. The device of claim 2, wherein the controller is configured to control access to the treatment chamber by the peripheral blood.

4. The device of claim 2, wherein the one or more reactive components include one or more of a denaturing agent, a degradative agent, binding agent, or an energy source.

5. The device of claim 1, wherein the means for modulating a physiological effect of the one or more inflammatory mediators include the controller configured to control interaction between one or more reactive components and the one or more inflammatory mediators, the one or more reactive components configured to alter a functional structure of the one or more inflammatory mediators in the peripheral blood.

6. The device of claim 5, wherein the controller is in communication with a reservoir configured to release the one or more reactive components into the peripheral blood.

7. The device of claim 5, wherein the one or more reactive components include one or more of a denaturing agent, a degradative agent, a binding agent, or an energy source.

8. The device of claim 7, wherein the one or more binding agents include one or more of antibodies, receptors, or cognates configured to bind to at least one of the one or more inflammatory mediators.

9. The device of claim 7, wherein the one or more binding agents include one or more of lectin, binding protein, catalytic antibody, catalytic aptamer, protease conjugate, or photoactivatable agent conjugate.

10. The device of claim 1, wherein the target value includes a desired concentration of the one or more inflammatory mediators in the peripheral blood.

11. The device of claim 1, wherein the target value includes a desired range of concentrations of the one or more inflammatory mediators in the peripheral blood.

12. The device of claim 1, wherein the target value includes a desired ratio of concentrations of two or more inflammatory mediators in the peripheral blood.

13. The device of claim 1, wherein the target value includes a desired ratio of levels of two or more inflammatory mediators in the peripheral blood.

14. The device of claim 1, wherein the sensor and the controller are configured to control levels of the one or more inflammatory mediators to substantially attain the target value.

15. The device of claim 1, wherein the sensor and the controller are configured to control levels of the one or more inflammatory mediators to limit a deviation from the target value.

16. The device of claim 15, wherein the deviation is determined by a weighted least squares fit.

17. The device of claim 1, wherein the sensor includes a biosensor, chemical sensor, physical sensor, or optical sensor.

18. The device of claim 17, wherein the sensor includes one or more of an aptamer, antibody, or receptor.

19. The device of claim 17, wherein the sensor includes one or more of a recognition-based substrate, an aptamer-based substrate, an antibody-based substrate, surface plasmon resonance, genetically-modified cells, or genetically-modified cells with receptor-linked signaling.

20. The device of claim 19, wherein the genetically-modified cells include receptor-linked signaling by fluorogen-activating proteins.

21. The device of claim 1, wherein the sensor is configured to target the device to a site having an elevated level of the inflammatory mediators.

22. The device of claim 1, wherein the sensor is configured to detect cytokines, T-lymphocytes, B-lymphocytes, or antibodies.

23. The device of claim 1, wherein the sensor is configured to detect body temperature, vital signs, edema, oxygen level, or pathogen/toxin level of the subject.

24. The device of claim 1, wherein the sensor is configured to detect one or more of anaphylatoxin, cytokine, chemokine, leukotriene, prostaglandin, complement, coagulation factor, or proinflammatory cytokine.

26. The device of claim 4, wherein the one or more binding agents on a matrix adapted to the treatment chamber are configured to sequester at least one of the one or more inflammatory mediators from the blood.

27. The device of claim 26, wherein the one or more binding agents include one or more of antibodies, receptors, or cognates configured to bind to at least one of the one or more inflammatory mediators.

28. The device of claim 26, wherein the one or more binding agent includes at least one of lectin, binding protein, catalytic antibody, catalytic aptamer, protease conjugate, or photoactivatable agent conjugate.

29. The device of claim 26, wherein the matrix includes one or more of a specific binding ligand or a hydrophobic surface.

30. The device of claim 26, wherein the matrix includes one or more of beads, cells, vesicles, filters, hydrogel polymers, microparticles, nanoparticles, adsorbent, or synthetic polymers.

31. The device of claim 29, wherein the specific binding ligand or the hydrophobic surface includes one or more of nucleic acid aptamers, peptide aptamers, molecular imprinting polymer, antibodies or fragments thereof, high affinity mimetics, synthetic binding molecules, or receptor binding molecules.

32. The device of claim 26, wherein the matrix includes one or more of a lectin, binding protein, receptor, antibody, catalytic antibody, catalytic aptamer, protease conjugate, or photoactivatable agent conjugate.

33. The device of claim 1, wherein the means for modulating a physiological effect of the one or more inflammatory mediators includes one or more reactive components configured to alter a functional structure of the one or more inflammatory mediators in the peripheral blood, wherein the one or more reactive components is configured to decrease an activity of one or more of TNF-α

, IL-1, IL-1β

, IL-6, IL-8, IL-10, IL-12, LPB, IFN-γ

, LIF, MIF, MCP-1, C3-a, C5-a, exotoxin, or endotoxin.

35. The device of claim 4, wherein the one or more reactive components increases an activity of an intermediate which decreases the activity of one or more of TNF-α

, IL-1, IL-1β

, IL-6, IL-8, IL-10, IL-12, LPB, IFN-γ

, LIF, MIF, MIP-1, MCP-1, C3-a, C5-a, exotoxin, or endotoxin.

36. The device of claim 4, wherein the one or more reactive components decreases an activity of an intermediate which decreases the activity of one or more of TNF-α

, IL-1, IL-1β

, IL-6, IL-8, IL-10, IL-12, LPB, IFN-γ

, LIF, MIF, MIP-1, MCP-1, C3-a, C5-a, exotoxin, or endotoxin.

37. The device of claim 1, wherein the means for modulating a physiological effect of the one or more inflammatory mediators includes one or more reactive components configured to alter a functional structure of the one or more inflammatory mediators in the peripheral blood, wherein the one or more reactive components is configured to modulate an activity of one or more of anaphylatoxins, cytokines, chemokines, leukotrienes, prostaglandins, complement, coagulation factors, or proinflammatory cytokines.

40. The device of claim 7, wherein the one or more reactive components increases an activity of an intermediate which decreases the activity of one or more of TNF-α

, IL-1, IL-1β

, IL-6, IL-8, IL-10, IL-12, LPB, IFN-γ

, LIF, MIF, MIP-1, MCP-1, C3-a, C5-a, exotoxin, or endotoxin.

41. The device of claim 7, wherein the one or more reactive components decreases an activity of an intermediate which decreases the activity of one or more of TNF-α

, IL-1, IL-1β

, IL-6, IL-8, IL-10, IL-12, LPB, LIF, MIF, MIP-1, MCP-1, C3-a, C5-a, exotoxin, or endotoxin.

42. The device of claim 7, wherein the one or more reactive components is configured to modulate an activity of one or more of anaphylatoxins, cytokines, chemokines, leukotrienes, prostaglandins, complement, coagulation factors, or proinflammatory cytokines.

43. The device of claim 1, wherein the one or more reactive components configured to alter a functional structure of the one or more inflammatory mediators in the peripheral blood includes an acoustic energy source or an electronic energy source.

44. The device of claim 43, wherein the energy source includes ultrasound.

46. The device of claim 4, wherein the energy source includes at least one of microwave irradiation, gamma irradiation, electron beam irradiation, vibrational/frequency irradiation, or atmospheric pressure glow discharge.

47. The device of claim 46, wherein the vibrational/frequency irradiation includes a set of differing energy inputs specifically directed to the one or more inflammatory mediators, wherein the set of differing energy inputs selectively resonates a plurality of resonant structures in the one or more inflammatory mediators, and wherein the resonance controllably alters or reduces the activity of the one or more inflammatory mediators in the peripheral blood of the subject.

48. The device of claim 47, wherein the one or more inflammatory mediators are modified with a functional group configured to be responsive to the set of differing energy inputs.

52. The device of claim 4, wherein the one or more degradative agents include at least one of an enzyme, coenzyme, enzyme complex, catalytic antibody, proteasome, strong acid, strong base, radical, photoactivatable agent, drug, cell, or radical ion.

54. The device of claim 7, wherein the one or more degradative agents include at least one of an enzyme, coenzyme, enzyme complex, catalytic antibody, proteasome, strong acid, strong base, radical, photoactivatable agent, drug, cell, or radical ion.

63. The device of claim 2, wherein the treatment chamber includes a source for producing the one or more reactive components.

64. The device of claim 63, wherein the source includes at least one reservoir and at least one producer.

65. The device of claim 64 wherein the at least one producer includes at least one encapsulated cell.

66. The device of claim 65, wherein the at least one encapsulated cell produces the one or more reactive components.

74. The device of claim 2, wherein the treatment chamber includes one or more reservoirs including one or more reactive components.

75. The device of claim 4, wherein the one or more reactive components include at least one modulator of the one or more inflammatory mediators configured to alter the functional structure of the one or more inflammatory mediators in the peripheral blood of the subject.

80. The device of claim 7, wherein the one or more reactive components include at least one modulator of the one or more inflammatory mediators configured to alter the functional structure of the one or more inflammatory mediators in the peripheral blood of the subject.

87. The device of claim 1, wherein the device is intracorporeal.

91. The device of claim 1, wherein the device is extracorporeal.

25. (canceled)

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