US 20120039884Al (19) United States (12) Patent Application Publication Watson et al. (54) COMPOSITIONS AND METHODS FOR TREATING CARDIOVASCULAR DISEASE (75) Inventors: A61P 9/10 A61K 39/395 A61P 11/00 A61P 25/10 Richard L. Watson, McPherson, KS (US); Anthony B. Wood, Dallas, TX (US); Gregory J. Archambeau, Puyallup, WA (US) (10) Pub. No.: US 2012/0039884 A1 (43) Pub. Date: Feb. 16, 2012 (52) (2006.01) (2006.01) (2006.01) (2006.01) US. Cl. ................. .. 424/134.1; 424/600; 424/158.1; 424/649 (73) Assignee: Revalesio Corporation, Tacoma, WA (US) (21) Appl. No.: 13/209,154 related conditions and symptoms (e.g., cardiac arrhythmia, vascular disease, myocardial infarction, congestive heart fail (22) Filed: Aug. 12, 2011 ure, myocarditis, atherosclerosis, and restenosis), comprising Related US. Application Data administering to a subject in need thereof a therapeutically effective amount of an electrokinetically altered aqueous ?uid as described herein. In particular aspects, the electroki netically altered aqueous ?uids comprise an ionic aqueous (60) Provisional application No. 61/373,494, ?led on Aug. 13, 2010, provisional application No. 61/485,071, ?led on May 11,2011. Publication Classi?cation (51) Int. Cl. A61K 33/00 A61P 35/00 A61P 29/00 A61P 25/00 A61K 33/24 A61P 25/16 A61P 3 7/02 (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (2006.01) (57) ABSTRACT Provided are methods for treating cardiovascular diseases and solution of charge-stabilized oxygen-containing nanostruc tures predominantly having an average diameter of less than about 100 nanometers and su?icient to provide modulation of at least one of cellular membrane potential and cellular mem brane conductivity. Provided are routes of administration or formulations for the electrokinetically-altered ?uids (e. g., electrokinetically-altered gas-enriched ?uids and solutions) and therapeutic compositions, along With use of the electro kinetically altered aqueous ?uids in surgical contexts, includ ing but not limited to cardiovascular related surgeries. Addi tionally provided are methods for measuring biological activity of electrokinetically altered ?uids. Patent Application Publication Feb. 16, 2012 Sheet 1 0f 42 Za 3a Em US 2012/0039884 A1 E a; E Em w W. W N yam n aim E aim slum m km m Patent Application Publication Feb. 16, 2012 Sheet 2 0f 42 mm £2) Q QBQ @ 9 w a 53 C) (.13 a... a a z a Q US 2012/0039884 A1 Patent Application Publication Feb. 16, 2012 Sheet 3 0f 42 US 2012/0039884 A1 5ia.},ekvlhpbi w mm mm”. mm mm mm, m Patent Application Publication ogWumSMiaz2w3?oq4umnv amp amp Feb. 16, 2012 Sheet 4 0f 42 US 2012/0039884 A1 Patent Application Publication 0C) mg '33 @mw Feb. 16, 2012 Sheet 5 0f 42 cm @OOGE) O mm 3. mam Q3 2: , mm US 2012/0039884 A1 Patent Application Publication C) mgS$owWaszhno6pqu@mgwa? GS QOQDOU Feb. 16, 2012 Sheet 6 0f 42 US 2012/0039884 A1 Patent Application Publication ‘iii Q5 @ Q Feb. 16, 2012 Sheet 7 0f 42 US 2012/0039884 A1 Patent Application Publication QOUO (/23 3 Feb. 16, 2012 Sheet 8 0f 42 @309 US 2012/0039884 A1 Patent Application Publication mm” Feb. 16, 2012 Sheet 9 0f 42 US 2012/0039884 A1 Patent Application Publication Q3 @ Feb. 16, 2012 Sheet 10 0f 42 £13 £9 memooca womnw 96m mom; soc; mam 25m cm mw gm; an US 2012/0039884 A1 Patent Application Publication wmoim wow; gm; wow Feb. 16, 2012 Sheet 11 0f 42 @Q N @ “3% was“ w mum US 2012/0039884 A1 a Patent Application Publication m; C3 C3 QQOQ @Q % Feb. 16, 2012 Sheet 12 0f 42 Patent Application Publication Feb. 16, 2012 Sheet 14 0f 42 US 2012/0039884 A1 GZWS MEWS it "In WM! S AU 0"I: v 8 $6 awixmowa Q WM) NEWS WAQGGWE Emgmagma iVAGQD'WE E uwmews @QCDQUQQ mm @NWWWWN wn" c: :3 :3 an m w g; £32 Patent Application Publication S$OBALU1W6E7N5~Q0 6%BA6L1276?nG Feb. 16, 2012 Sheet 16 0f 42 US 2012/0039884 A1
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