USOO8802596B2 (12) United States Patent (10) Patent No.: US 8,802,596 B2 Rogers et al. (45) Date of Patent: Aug. 12, 2014 (54) MULTI-FUNCTIONAL IONIC LIQUID (58) Field of Classification Search COMPOSITIONS FOR OVERCOMING None POLYMORPHISMAND IMPARTING See application file for complete search history. IMPROVED PROPERTIES FORACTIVE PHARMACEUTICAL, BIOLOGICAL, NUTRITIONAL AND ENERGETIC (56) References Cited INGREDIENTS U.S. PATENT DOCUMENTS Inventors: (75) Robin D. Rogers, Tuscaloosa, AL (US); 1943,176 A 1/1934 Graenacher Daniel T. Daly, Tuscaloosa, AL (US); 3,223,704 A 12, 1965 Shibe Richard P. Swatloski, Tuscaloosa, AL 3,344,018 A 9, 1967 Shibe (US); Whitney L. Hough-Troutman, 3.414,569 A 12/1968 Wieden Tuscaloosa, AL (US); James Hilliard 3.47 1423 A 10, 1969 Elmer 4,097.666 A 6, 1978 Johnson et al. Davis, Jr., Mobile, AL (US); Marcin 4,104,368 A 8, 1978 Lala et al. Smiglak, Tuscaloosa, AL (US); Juliusz 4,188,263. A 2, 1980 Hulsmann et al. Pernak, Pozan (PL); Scott K. Spear, 4,224,319 A 9, 1980 Marcadet Bankston, AL (US) 4,228, 162 A 10, 1980 Luzzi et al. 4,491,574 A 1/1985 Seifter et al. (73) Assignee: Board of Trustees of the University of 4,520,105 A 5, 1985 Sinner et al. Alabama, Tuscaloosa, AL (US) 4,637,830 A 1/1987 Dyer et al. 4,761,164 A 8, 1988 Pez et al. (*) Notice: Subject to any disclaimer, the term of this 4,973,456 A 1 1/1990 Quinn et al. patent is extended or adjusted under 35 5,175,353 A 12/1992 Jones et al. U.S.C. 154(b) by 0 days. 5,221,758 A 6/1993 Maynard 5,246,716 A 9, 1993 Sedun et al. (21) Appl. No.: 13/491,053 5,275,820 A 1/1994 Chang 5,428,000 A 6/1995 Innami et al. (22) Filed: Jun. 7, 2012 5,654,337 A 8, 1997 Roentsch et al. (65) Prior Publication Data 5,679,146 A 10, 1997 Kalt et al. 5,683,832 A 11/1997 Bonhote et al. US 2012/O264605 A1 Oct. 18, 2012 (Continued) Related U.S. Application Data FOREIGN PATENT DOCUMENTS (62) Division of application No. 1 1/545,938, filed on Oct. 10, 2006, now Pat. No. 8,232,265. CA 2619367 T 2009 (60) Provisional application No. 60/764,850, filed on Feb. DE 93-43O8410 3, 1993 2, 2006, provisional application No. 60/724,604, filed (Continued) on Oct. 7, 2005, provisional application No. 60/724,605, filed on Oct. 7, 2005. OTHER PUBLICATIONS Int. C. Office Action for Application No. JP 2008-534766 dated Sep. 13, (51) 2012. AOIN 57/18 (2006.01) Avent et al., Evidence for hydrogen bonding in solutions of 1-Ehtyl AOIN 43/707 (2006.01) 3-imidazolium Halides, and its implications for ambient temperature AOIN 43/66 (2006.01) Halogenoaluminate (III) ionic liquids, J. Chem. Soc. Dalton Trans. AOIN 43/68 (2006.01) 3405-3413 (1994). AOIN 43/58 (2006.01) Bates et al., CO2 capture by a task-specific ionic liquid, J. Am. Chem AOIN 43/82 (2006.01) Soc., 124(6):926-927 (2002). AOIN 43/78 (2006.01) AOIN 43/76 (2006.01) (Continued) AOIN 43/80 (2006.01) AOIN 43/653 (2006.01) Primary Examiner — Alton Pryor AOIN 43/10 (2006.01) (74) Attorney, Agent, or Firm — Meunier Carlin & Curfman, AOIN37/00 (2006.01) LLC AOIN37/18 (2006.01) AOIN33/18 (2006.01) AOIN 43/90 (2006.01) (57) ABSTRACT AOIN 43/54 (2006.01) Disclosed are ionic liquids and methods of preparing ionic AOIN 43/40 (2006.01) liquid compositions of active pharmaceutical, biological, AOIN 43/42 (2006.01) nutritional, and energetic ingredients. Also disclosed are AOIN 43/48 (2006.01) methods of using the compositions described herein to over (52) U.S. C. come polymorphism, overcome solubility and delivery prob USPC ........... 504/206:504/229; 504/231:504/232: lems, to control release rates, add functionality, enhance effi 504/236:504/238; 504/262:504/267: 504/270; cacy (synergy), and improve ease of use and manufacture. 504/271; 504/272; 504/289; 504/307: 504/334; 504/347; 504/241; 504/243; 504/244; 504/247; 504/253: 504/255 13 Claims, 6 Drawing Sheets US 8,802,596 B2 Page 2 (56) References Cited Bernstein, Crystal structure prediction and polymorphism, ACA Transactions, 39:14-23 (2004). U.S. PATENT DOCUMENTS Black et al., Increased chemical purity using a hydrage, Crystal Growth & Design, 4(3):539-544 (2004). 5,731, 101 A 3, 1998 Sherifet al. Bonhote et al., Hydrophobic, highly conductive ambient-temperature 5,792,399 A 8, 1998 Miester et al. 5,827,602 A 10, 1998 Koch et al. molten salts, Inorg. Chem., 35:1 168-1178 (1996). 5,856,513 A 1/1999 Ueet al. Bowlas et al., Liquid crystalline ionic liquids, Chem. Comm., 1625 5,908,697 A 6, 1999 Roux et al. 1626 (1996). 6,759,544 B2 7/2004 Burgard Browning et al., Relationships between antiseptic action and chemi 6,774,240 B2 8, 2004 Seddon et al. cal constitution with special reference to compounds of the pyridine, 6,808,557 B2 10/2004 Holbrey et al. quinoline, acridine and phenazine seriers, Proc. Royal Soc. London, 6,824,599 B2 11/2004 Swatloski et al. 6,846,926 B1 1/2005 Koppes et al. 93(653):329-366 (1922). 6,906,004 B2 6, 2005 Parrish et al. Browning et al., The antiseptic properties of the amino derivatives of 6,939,882 B1 9, 2005 Cooke et al. styryl and anil quinoline, Proc. Royal Soc. London, 100(703):293 6,939,974 B2 9, 2005 Earle et al. 325 (1926). 2002/0010291 A1 1/2002 Murphy Butcher et al., Initial Screening trials of some quaternary ammonium 2002/0019314 A1 2/2002 Frisch et al. .................. 504,358 compounds and amine salts as wood preservatives, For. Prod. J., 2002fO115569 A1 8, 2002 Schnabel et al. 2002/0161261 A1 10, 2002 Bahrmann et al. 27:19-22 (1977). 2003, OO73604 A1 4/2003 McGolfetal. Butcher et al., Efficacy of acidic and alkaline solutions of alkylam 2004.0007693 A1 1/2004 Moulton monium compounds as wood preservatives, J. Forestry Sci., 8:403 2004/0026666 A1 2, 2004 Chauvin et al. 409 (1978). 2004/O146549 A1 7/2004 Ben-Sesson et al. Campanella et al., Benzylpenicillin PVC membrane electrode for the 2004/0234966 A1 1 1/2004 Bryning et al. determination of antibiotics in formulations, J. Pharm. Biomed. 2005/OO587O2 A1 3/2005 Ben-Sasson et al. Analysis, 6(3):299-305 (1988). 2005. O136103 A1 6/2005 Ben-Sasson et al. 2005, 0194561 A1 9, 2005 Davis Campanella et al., Polymeric membrane electrodes for drug analysis, 2005/0232981 A1 10, 2005 Ben-Sasson J. Pharm Biomed. Analysis, 6:717-723 (1988). 2006/01 18755 A1 6/2006 Fujioka et al. Carmichael. A solution in sight, Chem. Britia, 36 (2000). 2006, O159632 A1 7/2006 Ishibashi et al. Carter et al., Sweet Success: Ionic liquids derived from non-nutritive 2007/0053939 A1 3/2007 Yokoyama et al. Sweeteners, Chem. Comm., 630-631 (2004). 2007/0054952 A1 3/2007 Hamamoto et al. Chawala et al., Challenges in polymorphism of pharmaceuticals, 2008. O190013 A1 8/2008 Argyropoulos 2008/0207452 A1* 8, 2008 Kramer et al. ................ 504,127 CRISPS, 5(1):9-12 (2004). 2009,0264664 A1 10, 2009 Endo et al. Cole et al., Novel Bronstead acidic ionic liquids and their use as dual 2010, 0004608 A1 1/2010 Hamamoto et al. solvent catalysts, J. Am. Chem. Soc., 124:5962-5963 (2002). 2010.00297.04 A1 2/2010 Hanma et al. Cuppen et al., Crystal structure and growth behavior of aspartame 2010/0280090 A1 11/2010 Hamamoto et al. form I-A, Crystal Growth & Design, 5(3):917-923 (2005). Davis et al. Thiazolium-ion based organic ionic liquids (OILS). FOREIGN PATENT DOCUMENTS Novel OILs which promote the benzoinc condensation, Tetrahedron Lett., 40: 1621-1622 (1999). ES 8406412 4f1983 Davis et al., From curiosities to commodities: Ionic liquids begin the FR 1404697 5, 1965 transformation, Chem. Comm. 1209-1212 (2003). GB 869149 5, 1961 Domagk, A new class of disinfectants, Deut. Med. Wochenschr, GB 1067094 5, 1964 GB 1473.603 5, 1977 61:829-832 (1935). JP 61-236818 10, 1986 Dupont et al., Room temperature molten salts: Neuteric "Green” JP 62-198609 9, 1987 Solvents for chemical reactions and processes, Braz. Chem. Soc. JP 63-0565O1 3, 1988 11(4):337-344 (2000). JP 2OO1525820 3, 2005 Elaiwi et al., Hydrogen bonding in Imidazolium salts and its impli JP 2005082512 3, 2005 cations for ambient-temperature Halogenoaluminate (III) ionic liq NL 3O2478 10, 1965 uids, J. Chem. Soc. Dalton Trans., 3467-3472 (1995). WO 91f13552 9, 1991 Extended European Search Report for Application No. 06774039.9 WO 95/21806 8, 1995 dated Jul. 8, 2011. WO 95/21871 8, 1995 Fannin et a. Properties of 1,3-Dialkylimidazolium chloride-alumi WO 95/21872 8, 1995 num chloride ionic liquids. 2. Phase transitions, densities, electrical WO 96.06593 3, 1996 WO 97,43012 11, 1997 conductivities, and viscosities, J. Phys. Chem.88:2614-2621 (1984). WO 98.51283 11, 1998 Fraga-Dubreuil et al., Grafted ionic liquid-phase-supported synthesis WO O3,O29329 4/2003 of small organic molecules, Tetrahedron Lett., 42:6097-6100 (2001). WO 2004 O75877 9, 2004 Freemantle, Ionic liquids show promise for clean separation technol WO 2005/0284.46 3, 2005 ogy, Chem. Eng. New, 76(34): 12 (1998). WO 2005/097731 10/2005 Freemantle, Eyes on ionic liquids, Chem.