Anti-inflammatory compositions and methods

• US 20100135984A1
• Filed: 12/02/2008
• Published: 06/03/2010
• Est. Priority Date: 12/02/2008
• Status: Abandoned Application

• Current Assignee: Searete LLC (Intellectual Ventures LLC)
• Original Assignee: Searete LLC (Intellectual Ventures LLC)
• Inventors: Wood, Lowell L. JR., Hyde, Roderick A., Sweeney, Elizabeth A., Malaska, Stephen L.
• Application Number:
  US12/315,515
• Publication Number:
  US 20100135984A1
• Time in Patent Office: Days
• US Class Current: 424/94.630
• CPC Class Codes: A61K 31/145 having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2) isothiourea A61K31/155
• CPC Class Codes: A61K 31/428 condensed with carbocyclic rings
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/4706 4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 33/06 Antimalarials
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Certain embodiments disclosed relate to compositions, including therapeutic compositions, methods, devices, and systems that modulate at least one inflammatory response or reaction. According to various embodiments, the compositions, methods, devices, and systems relate to modulating one or more of Toll-like receptors, Src family kinases, NF-kB molecules, proteases, or proteasomes.

Claims

1. A therapeutic composition, comprising:

at least one first agent configured to modulate the activity of one or more Toll-like receptors;

at least one second agent configured to modulate the activity of one or more NF-κ

B molecules; and

at least one pharmaceutically-acceptable carrier or excipient.

5. The therapeutic composition of claim 1, wherein the at least one first agent modulates the activity of MyD88.

7. The therapeutic composition of claim 1, wherein the at least one first agent inhibits the activity of one or more Toll-like receptors.

8. The therapeutic composition of claim 1, wherein the at least one second agent inhibits the activity of one or more NF-κ

B molecules.

11. The therapeutic composition of claim 1, wherein the at least one first agent includes at least one of chloroquine, M62812, or quinine.

16. The therapeutic composition of claim 1, wherein the at least one second agent includes one or more of disulfiram, ditiocarb, sulindac, sulfasalazine, or bortezomib.

17. The therapeutic composition of claim 1, further comprising at least one third agent configured to modulate the activity of one or more Src family kinases.

24. The therapeutic composition of claim 17, wherein the at least one third agent includes one or more of dasatinib, nilotinib, BMS-268770, UR-12947, aztreonam, MZ-338, riluzole, meloxicam, pramipexole, CBS-113-A, AZD0530, INNO-406, MK-0457, cediranib, sunitinib, bosutinib, axitinib, erlotinib, gefitinib, lapatinib, lestaurtinib, semaxanib, or imatinib.

27. The therapeutic composition of claim 1, further comprising at least one fourth agent configured to modulate the activity of at least one protease or proteasome.

29. The therapeutic composition of claim 27, wherein the at least one fourth agent includes one or more of saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir, or darunavir.

31. The therapeutic composition of claim 27, wherein the at least one fourth agent includes dichloroisocoumarin or bortezomib.

43. The therapeutic composition of claim 1, wherein the therapeutic composition is configured to modulate the production of at least one cytokine.

47. The therapeutic composition of claim 43, wherein the at least one cytokine includes one or more chemokines.

50. The therapeutic composition of claim 1, further comprising at least one of sulfadoxine-pyrimethamine, mefloquine, doxycycline, and atovaquone-proguanil, artemether, arteether, artelinic acid, artemotil, dihydroartemisin, dihydroartemisin-piperaquine, amodiaquine, lumefantrine, artesunate, artemisinin, or primaquine.

2-4. -4. (canceled)

6. (canceled)

9-10. -10. (canceled)

12-15. -15. (canceled)

18-23. -23. (canceled)

25-26. -26. (canceled)

28. (canceled)

30. (canceled)

32-42. -42. (canceled)

44-46. -46. (canceled)

48-49. -49. (canceled)

51-54. -54. (canceled)

55. A therapeutic composition comprising:

at least one of chloroquine, M62812, or quinine;

at least one of disulfiram, ditiocarb, sulindac, sulfasalazine, or bortezomib; and

at least one pharmaceutically-acceptable carrier or excipient.

56. The therapeutic composition of claim 55, further comprising one or more of dasatinib, nilotinib, BMS-268770, UR-12947, aztreonam, MZ-338, riluzole, meloxicam, pramipexole, CBS-113-A, AZD0530, INNO-406, MK-0457, cediranib, sunitinib, bosutinib, axitinib, erlotinib, gefitinib, lapatinib, lestaurtinib, semaxanib, or imatinib.

57. The therapeutic composition of claim 55, further comprising Cathepsin K.

58. The therapeutic composition of claim 55, further comprising dichloroisocoumarin or bortezomib.

59. The therapeutic composition of claim 55, further comprising at least one of sulfadoxine-pyrimethamine, mefloquine, doxycycline, atovaquone-proguanil, artemether, arteether, artelinic acid, artemotil, dihydroartemisin, dihydroartemisin-piperaquine, amodiaquine, lumefantrine, artesunate, artemisinin, or primaquine.

60. (canceled)

61. A method of modulating at least one immune response of one or more cells of a subject, comprising:

administering to the subject an effective amount of at least one therapeutic composition, including

at least one first agent configured to modulate the activity of one or more Toll-like receptors;

at least one second agent configured to modulate the activity of one or more NF-kB molecules; and

at least one pharmaceutically-acceptable carrier or excipient.

64. The method of claim 61, wherein the at least one first agent modulates the activity of MyD88.

70. The method of claim 61, wherein the at least one first agent includes at least one of cloroquine or quinine.

75. The method of claim 61, wherein the at least one second agent includes at least one of disulfiram, ditiocarb, sulindac, sulfasalazine, or bortezomib.

76. The method of claim 61, further comprising at least one third agent configured to modulate the activity of one or more Src family kinases.

83. The method of claim 76, wherein the at least one third agent includes one or more of dasatinib, nilotinib, BMS-268770, UR-12947, aztreonam, MZ-338, riluzole, meloxicam, pramipexole, CBS-113-A, AZD0530, INNO-406, MK-0457, cediranib, sunitinib, bosutinib, axitinib, erlotinib, gefitinib, lapatinib, lestaurtinib, semaxanib, or imatinib.

85. The method of claim 61, further comprising at least one fourth agent configured to modulate the activity of at least one protease or proteasome.

103. The method of claim 61, wherein the therapeutic composition is configured to modulate the production of at least one cytokine.

107. The method of claim 103, wherein the at least one cytokine includes one or more chemokines.

110. The method of claim 61, further comprising at least one of sulfadoxine-pyrimethamine, mefloquine, doxycycline, and atovaquone-proguanil, artemether, arteether, artelinic acid, artemotil, dihydroartemisin, dihydroartemisin-piperaquine, amodiaquine, lumefantrine, artesunate, artemisinin, or primaquine.

62-63. -63. (canceled)

65-69. -69. (canceled)

71-74. -74. (canceled)

77-82. -82. (canceled)

84. (canceled)

86-102. -102. (canceled)

104-106. -106. (canceled)

108-109. -109. (canceled)

111-131. -131. (canceled)

132. A method of modulating the activity of one or more Toll-like receptors and one or more NF-kB molecules of a subject, comprising:

administering to the subject an effective amount of at least one therapeutic composition, including at least one first agent configured to modulate the activity of one or more Toll-like receptors,

at least one second agent configured to modulate the activity of one or more NF-kB molecules; and

at least one pharmaceutically-acceptable carrier or excipient.

135. The method of claim 132, wherein the at least one first agent modulates the activity of MyD88.

136. The method of claim 135, wherein the at least one first agent inhibits the activity of MyD88.

141. The method of claim 132, wherein the at least one first agent includes at least one of chloroquine, M62812, or quinine.

146. The method of claim 132, wherein the at least one second agent includes one or more of disulfiram, ditiocarb, sulindac, sulfasalazine, or bortezomib.

147. The method of claim 132, further comprising at least one third agent configured to modulate the activity of one or more Src family kinases.

154. The method of claim 132, wherein the at least one second agent includes one or more of dasatinib, nilotinib, BMS-268770, UR-12947, aztreonam, MZ-338, riluzole, meloxicam, pramipexole, CBS-113-A. AZD0530, INNO-406, MK-0457, cediranib, sunitinib, bosutinib, axitinib, erlotinib, gefitinib, lapatinib, lestaurtinib, semaxanib, or imatinib.

156. The method of claim 132, further comprising at least one fourth agent configured to modulate the activity of at least one protease or proteasome.

174. The method of claim 132, wherein the therapeutic composition is configured to modulate the production of at least one cytokine.

178. The method of claim 174, wherein the at least one cytokine includes one or more chemokines.

181. The method of claim 132, further comprising at least one of sulfadoxine-pyrimethamine, mefloquine, doxycycline, and atovaquone-proguanil, artemether, arteether, artelinic acid, artemotil, dihydroartemisin, dihydroartemisin-piperaquine, amodiaquine, lumefantrine, artesunate, artemisinin, or primaquine.

133-134. -134. (canceled)

137-140. -140. (canceled)

142-145. -145. (canceled)

148-153. -153. (canceled)

155. (canceled)

157-173. -173. (canceled)

175-177. -177. (canceled)

179-180. -180. (canceled)

182-208. -208. (canceled)

209. A method of treating a subject afflicted with or suspected of being afflicted with malaria, comprising:

administering to a subject an effective amount of at least one therapeutic composition, including

at least one of chloroquine, M62812, or quinine;

at least one of disulfiram, ditiocarb, sulindac, sulfasalazine, or bortezomib; and

at least one pharmaceutically-acceptable carrier or excipient.

210. The method of claim 209, wherein the at least one therapeutic composition further includes one or more of dasatinib, nilotinib, BMS-268770, UR-12947, aztreonam, MZ-338, riluzole, meloxicam, pramipexole, CBS-113-A, AZD0530, INNO-406, MK-0457, cediranib, sunitinib, bosutinib, axitinib, erlotinib, gefitinib, lapatinib, lestaurtinib, semaxanib, or imatinib.

211. The method of claim 209, wherein the at least one therapeutic composition further includes Cathepsin K.

212. The method of claim 209, wherein the at least one therapeutic composition further includes dichloroisocoumarin or bortezomib.

213. The method of claim 209, wherein the at least one therapeutic composition further includes at least one of sulfadoxine-pyrimethamine, mefloquine, doxycycline, atovaquone-proguanil, artemether, arteether, artelinic acid, artemotil, dihydroartemisin, dihydroartemisin-piperaquine, amodiaquine, lumefantrine, artesunate, artemisinin, or primaquine.

214-215. -215. (canceled)