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

• US 20100217173A1
• Filed: 05/28/2009
• 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 8,206,330 B2
• Time in Patent Office: Days
• US Class Current: 604/5.10
• 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. Extracorporeal 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

1-38. -38. (canceled)

39. A method for treating an inflammatory disease or condition in a subject comprising:

providing an extracorporeal device including a treatment chamber configured to receive peripheral blood of the subject through a flow route, the treatment chamber including one or more reactive biological or chemical compounds that alter the functional structure of one or more inflammatory mediators in the peripheral blood.

40. The method of claim 39, wherein the one or more reactive biological or chemical compounds includes a denaturing agent, a degradative agent or a binding agent.

41. The method of claim 39, wherein the one or more reactive biological or chemical compounds decreases 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, MIP-1, MCP-1, C3-a, C5-a, exotoxin, or endotoxin.

42. The method of claim 39, wherein the one or more reactive biological or chemical compounds modulates an activity of an intermediate that modulates 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.

43. The method of claim 42, wherein the one or more reactive biological or chemical compounds increases an activity of an intermediate that 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.

44. The method of claim 42, wherein the one or more reactive biological or chemical compounds decreases an activity of an intermediate that 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.

45. The method of claim 40, wherein the one or more reactive biological or chemical compounds decreases an activity of one or more of anaphylatoxins, cytokines, chemokines, leukotrienes, prostaglandins, complement, coagulation factors, or proinflammatory cytokines.

46. The method of claim 40, wherein the denaturing agent includes an acid, base, solvent, cross-linking agent, chaotropic agent, disulfide bond reducer, enzyme, drug, cell, or radical ion.

47. The method of claim 40, wherein the degradative agent includes at least one of an enzyme, coenzyme, enzyme complex, catalytic antibody, proteasome, strong acid, strong base, radical, photoactivatable agent, drug, cell, or radical ion.

48. The method of claim 47, wherein the catalytic antibody generates the radical ion.

49. The method of claim 40, 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.

50. The method of claim 40, 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.

51. The method of claim 39, further including a sensor configured to detect the one or more inflammatory mediators in the peripheral blood.

52. The method of claim 51, further including a controller in communication with the sensor and configured to adjust the one or more reactive biological or chemical compounds to achieve a target value of the detected one or more inflammatory mediators in the peripheral blood of the subject.

53. The method of claim 64, wherein the controller is configured to control the interaction by modulating blood flow into the treatment chamber.

54. The method of claim 64, wherein the controller is configured to control the interaction by modulating release of the one or more biological or chemical compounds into the treatment chamber.

55. The method of claim 52, wherein the target value includes a desired concentration of the one or more inflammatory mediators in the peripheral blood.

56. The method of claim 52, wherein the target value includes a desired range of concentrations of the one or more inflammatory mediators in the peripheral blood.

57. The method of claim 52, wherein the target value includes a desired ratio of concentrations of two or more inflammatory mediators in the peripheral blood.

58. The method of claim 52, wherein the target value includes a desired ratio of levels of two or more inflammatory mediators in the peripheral blood.

59. The method of claim 52, wherein the sensor and the controller are configured to control levels of the one or more inflammatory mediators to substantially attain the target value.

60. The method of claim 52, 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.

61. The method of claim 60, wherein the deviation is determined by a weighted least squares fit.

62. The method of claim 51, wherein the sensor is configured to target the device to a site of inflammation in the subject.

63. The method of claim 51, wherein the sensor is configured to target the device to the site of inflammation and to an elevated level of the inflammatory mediators.

64. The method of claim 52, wherein the controller is configured to control interaction between the one or more reactive components and the one or more inflammatory mediators in the treatment chamber.

65. The method of claim 64, wherein the controller is configured to control access to the treatment chamber by the peripheral blood.

66. The method of claim 51, wherein the sensor includes a biosensor, chemical sensor, physical sensor, or optical sensor.

67. The method of claim 66, wherein the sensor includes one or more of an aptamer, antibody, or receptor.

68. The method of claim 66, 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.

69. The method of claim 68, wherein the genetically-modified cells include receptor-linked signaling by fluorogen-activating proteins.

70. The method of claim 51, wherein the sensor is configured to target the device to a site having an elevated level of the inflammatory mediators.

71. The method of claim 51, wherein the sensor is configured to detect cytokines, T-lymphocytes, B-lymphocytes, or antibodies.

72. The method of claim 51, wherein the sensor is configured to detect body temperature, vital signs, edema, oxygen level, or pathogen/toxin level of the subject.

73. The method of claim 51, wherein the sensor is configured to detect anaphylatoxins, chemokines, leukotrienes, prostaglandins, complement, coagulation factors, or proinflammatory cytokines.

74. The method of claim 73, wherein the sensor is configured to detect 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, exotoxins or endotoxins.

75-93. -93. (canceled)

94. A system comprising:

at least one computer program included on a computer-readable medium for use with at least one computer system wherein the computer program includes a plurality of instructions including, one or more instructions for determining at least one treatment of peripheral blood of a subject through an extracorporeal device including a treatment chamber configured to receive a peripheral blood through a flow route, the treatment chamber including one or more reactive biological or chemical compounds that alter a functional structure of one or more inflammatory mediators in the peripheral blood of the subject;

one or more instructions for receiving data including data from a sensor configured to detect the one or more inflammatory mediators in the peripheral blood; and

one or more instructions for receiving data including data from a controller for receiving the output of the sensor and configured to control interaction between the one or more biological or chemical compounds and the one or more inflammatory mediators in the treatment chamber;

wherein the sensor and the controller function relative to a target value of at least one of the one or more inflammatory mediators in the peripheral blood.

95. The system of claim 94, further including one or more instructions for sending or receiving data including data to or data from the controller informed by the sensor and configured to control interaction between the one or more reactive components and the one or more inflammatory mediators in the treatment chamber.

96. The system of claim 94, wherein the controller is configured to control the interaction by modulating blood flow into the treatment chamber.

97. The system of claim 94, wherein the controller is configured to control the interaction by modulating release of the one or more biological or chemical compounds into the treatment chamber.

98. The system of claim 94, wherein the one or more reactive biological or chemical compounds includes a denaturing agent, a degradative agent or a binding agent.

99. The system of claim 94, wherein the one or more reactive biological or chemical compounds decreases 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, MIP-1, MCP-1, C3-a, C5-a, exotoxin, or endotoxin.

101. The system of claim 94, wherein the one or more reactive biological or chemical compounds increases an activity of an intermediate that 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.

102. The system of claim 94, wherein the one or more reactive biological or chemical compounds decreases an activity of an intermediate that 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.

104. The system of claim 94, wherein the controller is configured to control interaction between the one or more reactive components and the one or more inflammatory mediators in the treatment chamber.

105. The system of claim 104, wherein the controller is configured to control the interaction by modulating blood flow into the treatment chamber.

106. The system of claim 104, wherein the controller is configured to control the interaction by modulating release of the one or more biological or chemical compounds into the treatment chamber.

107. The system of claim 94, wherein the target value includes a desired concentration of the one or more inflammatory mediators in the peripheral blood.

108. The system of claim 94, wherein the target value includes a desired range of concentrations of the one or more inflammatory mediators in the peripheral blood.

109. The system of claim 94, wherein the target value includes a desired ratio of concentrations of two or more inflammatory mediators in the peripheral blood.

110. The system of claim 94, wherein the target value includes a desired ratio of levels of two or more inflammatory mediators in the peripheral blood.

111. The method of claim 94, wherein the sensor and the controller are configured to control levels of the one or more inflammatory mediators to substantially attain the target value.

112. The method of claim 94, 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.

113. The method of claim 104, wherein the controller is configured to control access to the treatment chamber by the peripheral blood.

100. (canceled)

103. (canceled)