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(12) United States Patent (10) Patent No.: US 7.416,744 B2 Rubin Et Al

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(12) United States Patent (10) Patent No.: US 7.416,744 B2 Rubin Et Al USOO741674.4B2 (12) United States Patent (10) Patent No.: US 7.416,744 B2 Rubin et al. (45) Date of Patent: *Aug. 26, 2008 (54) EXTRACTS, COMPOUNDS AND 5,252,572 A 10, 1993 Hermecz et al. PHARMACEUTICAL COMPOSITIONS 5,270,342 A 12/1993 Brittain et al. HAVING ANT-DABETIC ACTIVITY AND 5,364,636 A 11, 1994 Ochi THEIR USE 5.430,060 A 7/1995 Brittain et al. 5.447,946 A 9, 1995 Kurono et al. 5,504,078 A 4/1996 Ducepetal. (75) Inventors: Ian Duncan Rubin, Nottingham (GB); 5,516,516 A 5/1996 Cherksey Jasjit Singh Bindra, Groton, CT (US); 5,605,698 A 2, 1997 Ueno Michael Anthony Cawthorne, Milton 5,693,327 A 12, 1997 Shah Keynes (GB) 5,698,199 A 12/1997 Mori et al. 5,728,704 A 3/1998 Mylarietal. (73) Assignee: Conopco, Inc., Englewood Cliffs, NJ 5,798, 101 A 8, 1998 Haveson (US) 5,824,668 A 10, 1998 Rubinfeld et al. 5,866.578 A 2/1999 Mylarietal. (*) Notice: Subject to any disclaimer, the term of this 5,908,609 A 6/1999 Lee et al. patent is extended or adjusted under 35 6,100,048 A 8, 2000 Cone et al. 6,309,853 B1 10/2001 Friedman et al. U.S.C. 154(b) by 0 days. 6,376,657 B1 4/2002 Van Heerden et al. 6,488.967 B1 12/2002 Hakkinen et al. This patent is Subject to a terminal dis 7,033,616 B2 * 4/2006 Rubinet al. claimer. 2002/0146468 A1 10, 2002 Rubin et al. (21) Appl. No.: 11/248,614 FOREIGN PATENT DOCUMENTS EP OOO69439 1, 1983 (22) Filed: Oct. 13, 2005 EP 010 1383. A 2, 1984 EP O123456 10, 1984 (65) Prior Publication Data EP O154639 9, 1985 US 2006/O159779 A1 Jul. 20, 2006 EP O21895.3 4f1987 (Continued) Related U.S. Application Data OTHER PUBLICATIONS (62) Division of application No. 09/891,615, filed on Jun. The Merck Manual of Diagnosis and Therapy, 17" Edition, 1999. 27, 2001, now Pat. No. 7,033,616. Editor, Keryn A.G. Lane. Merck & Co., Inc., Chapter 13, "Disorders of Carbohydrate Metabolism', pp. 165-185; and p. 1902.* (30) Foreign Application Priority Data Habeck M. Drug Discovery Today (Mar. 1, 2002), 7(5): 280-281. A Jun. 30, 2000 (GB) ................................. OO16213.1 succulent cure to end obesity.* Davies MJ et al., Diabetic Medicine (May 2004), 21(5): 403-414. (51) Int. Cl. Prevention of Type 2 diabetes mellitus. A review of the evidence and AOIN 65/00 (2006.01) its application in a UK setting. Sturis, Jet al., American Jof Physiology (1995), 269(4Pt 1):E786-92. C07. 4I/00 (2006.01) Prevention of diabetes does not completely prevent insulin secretion (52) U.S. Cl. ............................ 424/725; 514/866; 536/5 defects in the ZDF rat. (58) Field of Classification Search ....................... None Namiki et al., “Studies on the alpha-glucoside hydrolase inhibitor, See application file for complete search history. adiposin'. J. Antiobiotics, 35, pp. 1234-1236, (1982). J. B. Clarket al., “The diabetic Zucker fatty rat'. Proc. Soc. Exp. Biol. (56) References Cited Med. 173, pp. 68-75, (1983). Richard G. Peterson, “alpha-Glucosidase inhibitors in diabetes: les U.S. PATENT DOCUMENTS Sons from animal studies'. European Journal of Clinical Investiga 4,062,950 A 12/1977 Frommer et al. tion, 24. Suppl. 3, 11-18 (1994). 4,185,116 A 1, 1980 Barnish et al. J. H. Johnson et al., “Underexpression of beta cell high K, glucose 4,302.447 A 11, 1981 Horrobin transporters in non-insulin dependent diabetes'. Science, 250, pp. 4,302.477 A 1 1/1981 Mendy et al. 546-549, (1990). 4,393,049 A 7, 1983 Horrobin (Continued) 4,584.289 A 4, 1986 Jarreau et al. 4,652,553 A 3/1987 Hagmann et al. Primary Examiner Michele C. Flood 4,882,315 A 11, 1989 Chiodini et al. (74) Attorney, Agent, or Firm Morgan, Lewis & Bockius 4,883,410 A 11, 1989 Goddard et al. LLP 4,931,463 A 6, 1990 Barbier et al. 5,037,831 A 8, 1991 Malamas (57) ABSTRACT 5,066,659 A 1 1/1991 Lipinski 5,091,418 A 2f1992 Sawada et al. The invention relates inter alia to pharmaceutical composi 5,091,524 A 2/1992 Vértesy et al. tions containing an extract obtainable from a plant of the 5,157,116 A 10/1992 Ducep et al. genus Trichocaulon or Hoodia having anti-diabetic activity; 5,175,154 A 12/1992 Schwartz et al. and to the use of such extracts and to compound (1) as herein 5,175,186 A 12/1992 Barbier et al. defined and its analogues for the manufacture of medica 5, 192,772 A 3, 1993 Yoshikuni et al. ments having anti-diabetic activity. 5,217,877 A 6, 1993 Sawada et al. 5,246,960 A 9, 1993 Barbier et al. 1 Claim, No Drawings US 7.416,744 B2 Page 2 FOREIGN PATENT DOCUMENTS The Merck Manual of Diagnosis and Therapy, 17th Edition, 1999, Editor, Keryn A.G. Lane, Merck & Co., Inc., Chapter 13, Disorders of EP O219 156 4f1987 Carbohydrate Metabolism, pp. 165-185 and p. 1902. EP O2241.51 6, 1987 Thunberg, Charles Peter “Travels in Europe, Africa and Asia made EP O296.574 12, 1988 between the years 1770 and 1779.” vol. 2., F. and C. Rivington 1795, EP O749657 12/1996 pp. 140, 171. EP O7O3731 4f1998 Warburg, Otto “Die Pflazenwelt, Dritter Band” Bibliographisches EP 1 O99 444 A1 5, 2001 Institut Leipzig 1922, p. 146 (translation of highlighted section FR 2771 105 5, 1999 attached). HU P99 O2670 A 2, 2000 Marloth, R. “The Flora of South Africa with synopsis of the South HU P98 O3039 A 9, 2000 African genera of Phanerogamous plants' vol. III, pp. 1000-1002, JP 58194818 11, 1983 Wheldon & Wesley, London 1932. JP 8832O28 12/1996 Peterson, Richard G., “The Zucker diabetic fatty (ZDF) rat.” Lessons WO WO 85 OO970 3, 1985 from animal diabetes, V. Ed. E. Shafrir, pp. 225-230, (1995). WO WO90 14827 12/1990 Dohm, G. Lynis, et al., "Acarbose Treatment of Non-Insulin-Depen WO WO9424149 10, 1994 dent Diabetic Fatty (ZDF/Drtifa) Rats Restores Expression of Skel WO WO95 OOO41 1, 1995 etal Muscle Glucose Transporter GLUT4.” Drugs in Development, WO WO95 OO161 1, 1995 vol. I, O-Glucosidase Inhibition. Potential Use in Diabetes, pp. 173 WO 96.39384 12/1996 180 (1993). WO WO 97 15671 5, 1997 Tschesche et al. (1964) Uber Digitanolglykoside—IX (1) Zur WO WO97 47316 12/1997 Konstitution des Digipurpurogenin, Tetrahedron Letters 9:473-480. WO WO981.0068 3, 1998 Smith, C. (1996) Common Names of South African Plants; Botanical WO WO98 20121 5, 1998 Survey Memoir No.35, pp. 34-38 (Ed. E. Percy Phillips, Estelle Van WO WO98 27113 6, 1998 Hoepen) Department of Agricultural Technical Services (Republic of WO WO98 28335 7, 1998 South Africa). WO WO9842747 10, 1998 Okietal. (1968) Intramolecular interaction between hydroxyl groups WO WO98,46243 10, 1998 and carbonyl moiety in keto-alcohols, Bulletin of the Chemical Soci ety of Japan 41: 176-182. OTHER PUBLICATIONS Hill, B.C.F. (1969) Hoodia Gordonii, Nat. Cact, and Succ. Journal Y. Lee et al., “Beta-cell lipotoxicity in the pathogenesis of non 24(3):69-70. insulin dependent diabetes mellitus of obese rats: impairment in Millspaugh, C.F. (1974) American Medicinal Plants, pp. 534-543, adipocyte-beta-cell relationships'. Proc. Natl. Acad. Sci. USA, Dover Publications, Inc., New York. 91(23), pp. 10878-10882, (1994). Coombes, A.J. (1985) Dictionary of Plant Names, p. 31. Timber Press J. L. Milburn et al., “Beta-cell GLUT-2 loss and non-insulin depen Inc., Portland, Oregon. dent diabetes mellitus: current status of the hypothesis”. (Review) Foster et al. (1990) A Field Guide to Medicinal Plants, Eastern and Diabetes Metab, Rev. 9(3), pp. 231-236, (1993). Central North America, pp. 136-154, Houghton Mifflin Company, T. R. Pieber et al., “Amylin-insulin relationships in insulin resistance Boston. with and without diabetic hyperglycemia', Am. J. Physiol. 265(3 Pt. Bruyns, P. (1993) New combinations in Hoodia and Lavrania 1), pp. E446-E453, (1993). (Ascelpiadaceae Stapelieae), South African Journal of Botany L. J. Slieker et al., “Glucose transporter levels in tissues of sponta 59(3):342. neously diabetic Zucker falfa rat (ZDF/Drt) and viable yellow mouse Swarupanandan et al.(1996) The subfamilial and tribal classification (Ayy4), Diabetes, 41, pp. 187-193, (1992). of the family Asclepiadaceae, Botanical Journal of the Linnaean J. Sturis et al., “Alterations in pulsatile insulin secretion in the Zucker Society 120:327-369. diabetic fatty rat'. Am. J. Physiol. (267 Endocrinol. Metab. 30), Douketis et al.(1999) Periodic health examination, 1999 update: I. E250-259, (1994). Detection, prevention and treatment of obesity, Canadian Medical J.E. Friedman et al., “Altered expression of muscle glucose trans Association Journal 160(4):513-525. porter GLUT4 in diabetic fatty Zucker rats (ZDF/Drt-fa).” Am. J. Kopelman, P. (1999) Prescribing for obesity, Journal of the Royal Physiol., 261 (Endocrinol. Metab. 24), E782-788 (1991). College of Physicians of London 33(1):31-32. M. Ohneda et al., “Caloric restriction in obese pre-diabetic rats pre Pappe, L. “A description of South African forest trees and arborescent vents beta-cell depletion, loss of beta-cell GLUT-2 and glucose shrubs used for technical and economical purposes' 1862 Ward & incompetence”. Diabetologia, 38(2), pp. 173-179, (1995). Co., London. Smith, Christo Albertyn "Common Names of South African Plants.” Laidler, P.W.
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