(19) TZZ ¥ ¥¥_T (11) EP 2 326 338 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 36/47 (2006.01) A61K 36/23 (2006.01) 05.08.2015 Bulletin 2015/32 A61K 36/89 (2006.01) A61K 36/37 (2006.01) A61K 36/48 (2006.01) A61K 36/906 (2006.01) (2006.01) (2006.01) (21) Application number: 09741450.2 A61K 36/29 A61K 36/22 A61K 36/72 (2006.01) A61K 36/59 (2006.01) A61K 36/899 (2006.01) (22) Date of filing: 17.09.2009 (86) International application number: PCT/IN2009/000510 (87) International publication number: WO 2010/032267 (25.03.2010 Gazette 2010/12) (54) A HERBAL FORMULATION FOR PREVENTION AND TREATMENT OF DIABETES AND ASSOCIATED COMPLICATIONS PFLANZLICHE FORMULIERUNG ZUR PRÄVENTION UND BEHANDLUNG VON DIABETES UND RELEVANTEN KOMPLIKATIONEN FORMULATION À BASE DE PLANTES POUR LA PRÉVENTION ET LE TRAITEMENT DU DIABÈTE ET DE COMPLICATIONS ASSOCIÉES (84) Designated Contracting States: GB-A- 190 505 856 JP-A- 10 127 256 AT BE BG CH CY CZ DE DK EE ES FI FR GB GR JP-A- 2000 080 044 JP-A- 2005 053 864 HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL JP-A- 2005 320 281 JP-A- 2006 008 528 PT RO SE SI SK SM TR JP-A- 2006 056 836 JP-A- 2006 104 094 JP-A- 2006 232 781 JP-A- 2007 097 500 (30) Priority: 22.09.2008 IN DE22212008 US-A- 4 826 684 US-A- 4 908 207 15.06.2009 IN DE12212009 US-A1- 2004 116 394 US-A1- 2006 018 978 15.06.2009 IN DE12222009 US-A1- 2008 206 372 15.06.2009 IN DE12232009 15.06.2009 IN DE12242009 • DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, (43) Date of publication of application: US; January 2002 (2002-01), ARUN N ET AL: 01.06.2011 Bulletin 2011/22 "Efficacy of turmeric on blood sugar and polyol pathway in diabetic albino rats" XP002572901 (73) Proprietor: Innoveda Biological Solutions (P) Ltd. Database accession no. PREV200200203967 Greater Kailash II, New Delhi-110 048 (IN) cited in the application • DATABASE EMBASE [Online] ELSEVIER (72) Inventor: KRISHNAN, G. Geetha SCIENCE PUBLISHERS, AMSTERDAM, NL; 1990, Patparganj, Delhi 110092 (IN) TANK R ET AL: "Antidiabetic activity of Curcuma longa (50% EtOh-extr.) in alloxan induced (74) Representative: Winter, Brandl, Fürniss, Hübner, diabetic rats" XP002572902 Database accession Röss, Kaiser, Polte - Partnerschaft mbB no. EMB-1990339134 Patent- und Rechtsanwaltskanzlei • DATABASE BIOSIS [Online] BIOSCIENCES Alois-Steinecker-Strasse 22 INFORMATION SERVICE, PHILADELPHIA, PA, 85354 Freising (DE) US; 15 September 1999 (1999-09-15), RANA T S ET AL: "Studies on indigenous herbal remedies (56) References cited: for diabetes mellitus in India" XP002572903 EP-A1- 1 723 960 EP-A1- 1 925 310 Database accession no. PREV200000163003 Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 326 338 B1 Printed by Jouve, 75001 PARIS (FR) (Cont. next page) EP 2 326 338 B1 • DATABASE BIOSIS [Online] BIOSCIENCES • MURALI Y K ET AL: "Antihyperglycemic effect of INFORMATION SERVICE, PHILADELPHIA, PA, water extract of dry fruits of Terminalia chebula US; April 1997 (1997-04), SHARMA S R ET AL: in experimental diabetes mellitus", MEDICINAL & "Hypoglycaemic potential of Mangifera indica AROMATIC PLANTS ABSTRACTS, SCIENTIFIC leaves in rats" XP002572904 Database accession PUBLISHERS, SCIENTIFIC PUBLISHERS, NEW no. PREV199800082356 cited in the application DELHI - INDIA, vol. 27, no. 2, 1 March 2005 • DATABASE WPI Week 200338 Thomson (2005-03-01), XP018004409, ISSN: 0250-4367 Scientific, London, GB; AN 2003-400672 • DATABASE BIOSIS [Online] BIOSCIENCES XP002575883 & RU 2 197 259 C1 (BUZLAMA V S) INFORMATION SERVICE, PHILADELPHIA, PA, 27 January 2003 (2003-01-27) US 2007 SENTHILKUMAR G P ET AL: ’Evaluation • DATABASE WPI Week 200904, Derwent of antioxidant potential of Terminalia chebula Publications Ltd., London, GB; AN 2009- A87141, fruits studied in streptozotocin- induced diabetic XP002575884 & KR 10 0 814 368 B1 (UNIV KOREA rats’Database accession no. PREV200700545382 IND & ACADEMIC COLLABORATION) 18 March & PHARMACEUTICAL BIOLOGY, vol. 45, no. 6, 2008 2007, pages 511-518, ISSN: 1388-0209, DOI: • DATABASE WPI Week 200419 Thomson 10.1080/13880200701446720 Scientific, London, GB; AN 2004-192362 XP002575885 & CN 1 444 939 A (SHENZHEN Remarks: CHINESE TRADITIONAL MEDICINE &) 1 October Thefile contains technical information submitted after 2003 (2003-10-01) the application was filed and not included in this • DATABASE WPI Week 200415 Thomson specification Scientific, London, GB; AN 2004-144588 XP002575886 & CN 1 456 259 A (MAO Y) 19 November 2003 (2003-11-19) • DATABASE WPI Week 200803, Derwent Publications Ltd., London, GB; AN 2008- A43864, XP002575904 & KR 2007 074 066 A (CHOI S G) 12 July 2007 2 1 EP 2 326 338 B1 2 Description proves the cell’s sensitivity to the presence of insulin, thereby improving the uptake of glucose into the Field of the invention cells, leading to better blood sugar control. [0001] The present invention relates to an herbal for- 5 iii) Insulin:-This is exogenously supplemented in the mulation for the prevention and treatment of diabetes and case of people suffering from both type I and type II the associated complications.. The present invention diabetes. particularlyrelates to an herbal formulation useful for con- trolling / reducing the blood glucose level significantly [0008] Diabetes is a lifestyle disease and cannot be and for the prevention / management / treatment of dia- 10 cured. The current therapies mentioned above are there- betes related complications. The formulation of the fore only a blood sugar management mechanism. As di- present invention not only efficiently controls the Type 2 abetes is a chronic, long-duration disease, these drugs diabetes but also offers reversal possibilities in predia- need to be taken on a sustained basis. Currently, avail- betes and thereby a possible preventive option for Type able synthetic drugs suffer from concomitant side effects 2 diabetes mellitus and the associated complications. 15 caused due to long duration of usage. Literature survey [0002] The present invention also relates to a herbal indicates that cardiovascular mortality was higher in pa- formulation for the prevention and tratement of diabetes tients with oral hypoglycemics than in those treated with mellitus. diet and exercise alone or with insulin. Sulphonylureas [0003] The present invention also relates to a herbal cause hypoglycemia as a side effect. Biguanides cause formulation for prevention and treatment of renal compli- 20 lactic acidosis. Oral hypoglycemia-drugs also cause GIT cations associated with diabetes consequently reducing irritation, weight gain, hypertension, etc. On continuous the serum creatinine levels, which is elevated due to rea- and constant exertion, the diabetic person is also liable sons which can be attributed to the kidneys and their for pancreatic fatigue. In addition, it is also seen that many functional and structural integrity. of the existing drugs available lead to drug resistance in [0004] The present invention also relates to a herbal 25 patients with long durations of use. formulation for the prevention and treatment of retinop- [0009] The long-term complications of diabetes are athy associated with diabetes. The formulation of the more damaging. This is caused by spikes in blood sugar present invention not only efficiently controls thein patients during the day. Increased blood sugar even progress of diabetic retinopathy but also offers reversal for short periods leads to glycosylation of Hemoglobin. possibilities in such cases. 30 Glycosylated Hemoglobin causes long-term irreversible [0005] The present invention also relates to a herbal damages to eyes, kidneys, nerves and blood vessels. formulation for prevention and treatment of oxidative [0010] A wide-spread pathological complication of Di- damage to heart and its blood vessels associated with abetes is thickening of capillary basement membrane, diabetes useful for reducing oxidative damage caused increase in vessel wall matrix and cellular proliferation to the cardiac musculature and blood vessel walls, and 35 resulting in vascular complications like lumen narrowing, treating hypertension. early atherosclerosis, and sclerosis of glomerular capil- [0006] Diabetes Mellitus is the most prevalent meta- laries, retinopathy, neuropathy and peripheral vascular bolic disorder among humans with enormous implica- insufficiency. The level of glycosylated hemoglobin tions on social health and financial wealth. This is char- (HbA1c) is also increased in diabetes and is taken as an acterized by poor regulation of blood glucose levels in 40 index of protein glycosylation. It reflects the state of gly- human beings. Other than blood glucose levels the long caemia over the preceding 2 - 3 months. As such, there term effects of the disease involves all major systems is no drug available for the treatment of diabetic compli- and organs of the body including the Heart and blood cations. vessels, Kidneys, Liver, Eyes and the nervine systems. [0011] Further, diseases of the kidneys are very com- The improper nutrition of the cells due to lack of insulin, 45 mon now a days and it also occurs as complications or leads to structural and functional irregularities in the cells, secondary to chronic diseases such as diabetes and including the waste they generate and its management. heart diseases. Elevation of serum creatinine is a major Diabetes mellitus also predisposes cardiac failure and parameter to identify the structural and functional health renal failure. of the kidneys. There are no medicines available as on [0007] Presently, this disorder is managed by taking 50 todaywhich can improve the health of thedefunct kidneys drugs falling into the following categories: and thereby decrease the creatinine levels.