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(12) United States Patent (10) Patent No.: US 9,084,726 B2 Egberg Et Al USOO9084726B2 (12) United States Patent (10) Patent No.: US 9,084,726 B2 Egberg et al. (45) Date of Patent: Jul. 21, 2015 (54) SUSPENSION COMPOSITIONS OF 6,855.359 B2 2/2005 Khare PHYSIOLOGICALLY ACTIVE PHENOLC 3: R: 658. Hy st al COMPOUNDS AND METHODS OF MAKING 8,900,635- - - B2 12/2014 Elderer, etJr. al. et al. AND USING THE SAME 2004/0164194 A1 8/2004 Reed et al. 2004/022O11.6 A1* 11/2004 Behnam .......................... 514/27 (71) Applicant: Humanetics Corporation, Eden Prairie, 2006/01 1651.0 A1 6/2006 Behnam MN (US) 2006/0292214 A1* 12/2006 Jenkins et al. ................ 424/451 2007/002O197 A1 1/2007 Galli et al. 2007.0043.121 A1 2/2007 Brown et al. (72) Inventors: David C. Egberg, Bonita Springs, FL 2007/0087104 A1* 4/2007 Chanamai ..................... 426,602 (US); Michael D. Kaytor, Maplewood, 2007,0269.526 A1 11/2007 BOS et al. MN (US); John C. Dykstra, Eden 2008/0311209 A1 12/2008 Beumer et al. Prairie, MN (US) 2009.0035336 A1* 2, 2009 Volhardt et al. ............. 424/401 2009/0035366 A1* 2/2009 Liversidge et al. ........... 424/451 (73) Assignee: Humanetics Corporation, Minneapolis, 2012fO1641902012/O121654 A1 6,5, 2012 Ei.Elder, Jr. et al.al MN (US) (*) Notice: Subject to any disclaimer,- the term of this FOREIGN PATENT DOCUMENTS patent is extended or adjusted under 35 WO WO 2012/068140 5, 2012 U.S.C. 154(b) by 0 days. OTHER PUBLICATIONS (21) Appl. No.: 14/090,864 Atkinson, et al., “The effects of phytoestrogen isoflavones on bone (22) Filed: Nov. 26, 2013 density in women: a double-blind, randomized, placebo-controlled trial'', Am. J. Clin. Nutr., vol. 79, pp. 326-333, (2004). (65) Prior Publication Data (Continued) US 2015/O147359 A1 May 28, 2015 Primary Examiner — Robert A Wax (51) Int. Cl. Assistant Examiner — Melissa Mercier 3. Ig52 R (74) Attorney, Agent, or Firm — Stoel Rives, LLP: (2006.01) Zhi-Xiang (Alex) Oh (52) U.S. Cl. CPC ................. A61 K9/10 (2013.01); A61 K3I/352 (2013.01) (57) ABSTRACT (58) Field of Classification Search The present invention is directed to compositions comprising None physiologically active phenolic compounds and methods for See application file for complete search history. making and using the same. In particular embodiments, the compositions described herein include Suspension formula (56) References Cited tions including a physiologically active phenolic compound provided as a nanoparticulate material and dispersed within U.S. PATENT DOCUMENTS an edible lipid. 4,390,559 A * 6/1983 Zilliken ........................ 426,545 5,302.401 A 4, 1994 Liversidge et al. 30 Claims, 4 Drawing Sheets Genivida (before milling) 13 Meann SizeSi :35.7961.5cm) OO 12 Median Size : 29.54557(Lm) 90 Mode Size 27.8086{um) S.P. Area :2199.7(cnicm) 80 10 SDev, : 22.1223(um) Span : OFF 70 c 8 Diameter on Cumulative%: (1)10.00(%)- 17.1811 (um) s : (2)50.00(%)-29.5456(um) 60 S. q(%) 6 ; (5)99.00(%)-SE.00%). 92,25:E) 40so Sass: : (6)99.90%)- 181,0281(lam) SS 4. 30 20 2 O O O O. 0.100 1.000 1000 1000 1000 3OOO Diameterium) US 9,084.726 B2 Page 2 (56) References Cited Si, et al., “Improving the Anti-Tumor Effect of Genistein with a Biocompatible Superparamagnetic Drug Delivery System.” Journal OTHER PUBLICATIONS of Nanoscience and Nanotechnology, vol. 10, No. 4, pp. 2325-2331, (2010). Bhathena, et al., “Beneficial role of dietary phytoestrogens in obesity Sun, et al., “Pilot Study of a Specific Dietary Supplement in Tumor and diabetes'’.” Am. J. Clin. Nutr., vol. 76, pp. 1191-1201, (2002). Bearing Mice and in Stage IIIB and IV Non-Small Cell Lung Cancer Chait, A., “Low-Density Lipoprotein Oxidation and the Pathogenesis Patients.” Nutrition and Cancer, vol.39, No. 1, pp. 85-95, (2001). of Atherosclerosis.” WJM, vol. 160, No. 2, pp. 183-184, Feb. 1994. Takimoto, et al., “Phase I Pharmacokinetic and Pharmacodynamic Clifton-Bligh, et al., “The effect of isoflavones extracted from red Analysis of Unconjugated Soy Isoflavones Administered to Individu clover (Rimostil) on lipid and bone metabolism.” Menopause: The als with Cancer.” Cancer Epidemiology, Biomarkers & Prevention, Journal of The North American Menopause Society, vol. 8, No. 4, pp. vol. 12, pp. 1213-1221, (Nov. 2003). 259-265, (2001). Cotter, et al., “Genistein Appears to Prevent Early Postmenopausal Urban, et al., “The Effect of Isolated Soy Protein on Plasma Biomark Bone Loss as Effectively as Hormone Replacement Therapy.” Nutr ers in Elderly Men with Elevated Serum Prostate Specific Antigen.” tion Reviews, vol. 61, No. 10, pp. 346-351, (2003). The Journal Urology, vol. 165, pp. 294-300, (Jan. 2001). Fitzpatrick, L.A., “Soy isoflavones: hope or hype?,” Maturitas, vol. Wei, et al., “Isoflavone Genistein: Photoprotection and Clinical 44. Suppl. 1, pp. S21-S29, (2003). Implications in Dermatology'.” The Journal of Nutrition, vol. 133, Goodman-Gruen, et al., “Usual dietary isoflavone intake and body pp. 3811S-3819S. (2003). composition in postmenopausal women. Menopause: The Journal of Zhou, et al., “Genistein Stimulates Hematopoiesis and Increases the North American Menopause Society, vol. 10, No. 5, pp. 427-432, Survival in Irradiated Mice.” J. Radiat. Res., vol. 46, pp. 425-433, (2003). (2005). Landauer, et al., “Radioprotective and Locomotor Responses of Mice Office Action issued Mar. 21, 2012 in U.S. Appl. No. 12/946,711. Treated with Nimodipine Alone and in Combination with Response to the Mar. 21, 2012 Office Action filed Jun. 21, 2012, in WR-151327.” Journal of Applied Toxicology, vol. 21, pp. 25-31, U.S. Appl. No. 12/946,711. (2001). Office Action issued Aug. 31, 2012 in U.S. Appl. No. 12,946,711. Landauer, et al., “Genistein Treatment Protects Mice from Ionizing Response to the Aug. 31, 2012 Office Action filed Feb. 14, 2013, in Radiation Injury,” Journal of Applied Toxicology, vol. 23, pp. 379 U.S. Appl. No. 12/946,711. 385, (2003). Final Rejection issued Oct. 8, 2013, in U.S. Appl. No. 12,946,711. Landauer, et al., “Prevention of Gamma Radiation-Induced Mortality Office Action issued Mar. 28, 2012 in U.S. Appl. No. 13/411,405. in Mice by the Isoflavone Genistein.” NATO RTG-099, pp. 17-1-17 Response to the Mar. 28, 2012 Office Action filed Jun. 27, 2012, in 11, (2005). Leonarduzzi, et al., “Design and Development of Nanovehicle-Based U.S. Appl. No. 13/411,405. Delivery Systems for Preventive or Therapeutic Supplementation Office Action issued Sep. 11, 2012 in U.S. Appl. No. 13/411,405. with Flavonoids.” Current Medicinal Chemistry, vol. 17, pp. 74-95, Response to the Sep. 11, 2012 Office Action filed Dec. 11, 2012, in (2010). U.S. Appl. No. 13/411,405. Magee, et al., “Phyto-Oestrogens, their mechanism of action: current Third Office Action issued Feb. 22, 2013, in U.S. Appl. No. evidence for a role in breast and prostate cancer.” British Journal of 13/411,405. Nutrition, vol. 91, pp. 513-531, (2004). International Search Report and Written Opinion issued Mar. 23. Messina, M.J., “Emerging Evidence on the Role of Soy in Reducing 2012, in International Application No. PCT/US2011/060829. Prostate Cancer Risk.” Nutrition Reviews, vol. 61, No. 4, pp. 117 International Preliminary Report on Patentability issued May 21, 131. (Apr. 2003). 2013, in International Application No. PCT/US2011/060829. Mohammad, et al., “Genistein sensitizes diffuse large cell lymphoma Young, et al., “Why are Low-Density Lipoproteins Atherogenic.” to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) WJM, vol. 160, No. 2, pp. 153-164, Feb. 1994. chemotherapy.” Molecular Cancer Therapeutics, vol. 2, No. 12, pp. Applicant Initiated Interview Summary issued Dec. 14, 2012 in U.S. 1361-1368, (2003). Appl. No. 12/946,711. Morabito, et al., “Effects of Genistein and Hormone-Replacement Office Action issued Oct. 8, 2013 in U.S. Appl. No. 12/946,711. Therapy on Bone Loss in Early Postmenopausal Women: A Random Response to the Oct. 8, 2013 Office Action filed Mar. 7, 2014 in U.S. ized Double-Blind Placebo-Controlled Study,” Journal of Bone and Appl. No. 12/946,711. 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