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(12) Patent Application Publication (10) Pub. No.: US 2016/0220627 A1 MELNICK Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2016/0220627 A1 MELNICK Et Al US 2016O220627A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0220627 A1 MELNICK et al. (43) Pub. Date: Aug. 4, 2016 (54) EXTRACTS OF CURCUMAAMADA AND (57) ABSTRACT USES THEREOF (71) Applicants: DHARMA BIOMEDICAL, LLC, The invention concerns carbon dioxide extracts of Curcuna Miami, FL (US); FLAVEX amada (mango ginger), including Supercritical carbon diox NATUREXTRAKTE GMBH, ide extracts of Canada; methods for their production; com Rehlingen (DE) positions comprising the extracts; methods for treating or (72) Inventors: STEVEN J. MELNICK, CORAL delavingR E. (th OSUt Oof conditiN 1OS i h in 11 pproliferati GABLES, FL (US); KARL-WERNER IN inst l 1. al Ion, ec In 'E, 1p1 QUIRIN, BECKINGEN (DE); emia, nypercno esterolem1a, ypertrig yceridemia, nyperg CHEPPAIL RAMACHANDRAN, lycemia, platelet hyper-aggregation, immune disorder Such MIAMI, FL (US); MELVIN as autoimmune disorder, or neurodegenerative condition; and ROTHBERG, WESTON, FL (US) methods for inhibiting expression of Bcl-2. Bak, and p53 9. enes; inhibitingg expressioneXp of the COX-2 and NF-kB genes,9. (21) Appl. No.: 15/011,628 inhibiting production of phosphorylated target of rapamycin 1-1. (TOR), modulating AMP-activated protein kinase (AMPK), (22) Filed: Jan. 31, 2016 inhibiting protein kinase B (AKT) signaling, modulating the Related U.S. Application Data RaS/PI3K/PTENEMSso mTOR signalingRNA. andpathway. tly Another R (60) Eyal application No. 62/110,062, filed on Jan. aspect of the invention concerns a method for inhibiting con s tamination, comprising applying the extract or composition Publication Classification of the invention to a surface. Another aspect of the invention concerns a method for ppromoting glongeV1ty longevity of a cell invitro or (51) Int. Cl. in Vivo, comprising contacting a target cell in vitro or in vivo A6 IK36/9066 (2006.01) with an effective amount of the extract or composition of the A6 IK 45/06 (2006.01) invention. Another aspect of the invention concerns a method A6 IK3I/05 (2006.01) for promoting longevity of a subject, comprising administer SE 3. ing an effective amount of the extract or composition of the A6 IK3I/II 30 6. 8: invention. Another aspect of the invention concerns a method (52) U.S. Cl for inhibiting9. the metabolism of a cancer cell, comprisinpr1S1ng CPC - - - - - - - - A61K 36/9066 (2013.01): A0IN 65/48 contacting the target cancer cell in vitro or in vivo with an (2013.01); A61 K3I/II (2013.01); A61 K effective amount of the extract or composition of the inven 31/015 (2013.01); A61 K3I/01 (2013.01); tion. Another aspect of the invention concerns a kit including A61K 45/06 (2013.01); A61 K 2236/37 the extract or composition; a container containing the extract (2013.01) or composition; and packaging material. Patent Application Publication Aug. 4, 2016 Sheet 1 of 33 US 2016/0220627 A1 cities: o 8. 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S. o Patent Application Publication Aug. 4, 2016 Sheet 32 of 33 US 2016/0220627 A1 we'r'e'r'r'e'r'r'e'r'r'e'e'r:::::::::::::::::::::::::::::::::::::::::..................kssississississississississississississississississississ : : 8 $ 3 8 : 8 . x------------------------------------------------------------------------------------------------------------------------------------------------------------------ &83. 838. 8:::::::::S FIG. 35A Patent Application Publication Aug. 4, 2016 Sheet 33 of 33 US 2016/0220627 A1 : : & -Y FG. 35B US 2016/0220627 A1 Aug. 4, 2016 EXTRACTS OF CURCUMAAMADA AND Policegoudra et al. 2010) have identified difurocumenonol, a USES THEREOF new antimicrobial compound from mango ginger rhizome. The major chemical components of mango ginger rhizome CROSS-REFERENCE TO RELATED that have been reported include (E)-labda-8(17), 12-diene APPLICATION 15, 16 dial (Singh et al. 2010; Sheeja and Nair 2014), starch, phenolic acids, Volatile oils, curcuminoids and terpenoids 0001. The present application claims the benefit of U.S. like difurocumenonol, amadannulen and amadaldehyde (Po Provisional Application Ser. No. 62/110,062, filed Jan. 30, licegoudra et al. 2011). However, it is not clear whether 2015, which is hereby incorporated by reference herein in its curcuminoids are in fact a constituent of mango ginger rhi entirety, including any figures, tables, nucleic acid sequences, Zome which has a pale yellow color similar to ginger and not amino acid sequences, or drawings. orange as in turmeric. Discrepancies in the literature may occur, due in part to misidentification of raw materials. For BACKGROUND OF THE INVENTION example, species such as Curcoma mangga referred to as 0002 The genus Curcuma contains over 80 species of mango-like turmeric contains curcuminoids and (E)-labda rhizomatous herbs of which many have significant value as 8(17), 12-diene-15, 16 dial (Malek et al. 2011). Compounds medicines, dyes and spices (Islam 2004). Curcuma amada Such as difurocumenonol and amadaldehyde have been dem Roxb. is an important member of the genus commonly known onstrated to possess anticancer activity (Policegoudra et al. as mango ginger due to the raw mango-like aroma of the 2010; Gonzalzezet al. 2010). rhizome. It has a morphological and phylogenic resemblance with ginger (Zingiber officinale) but imparts mango BRIEF SUMMARY OF THE INVENTION (Mangifera indica) flavor. Mango flavor is in part attributed to 0004. The inventors have determined that a supercritical cis-ocimene among the 68 volatile aroma components carbon dioxide (CO) extract (CA) prepared from mango present in the essential oil of mango ginger rhizome (Achut ginger of (Curcuna amada) rhizomes has Superioranticancer and Bandyopadhyaya 1984; Srinivas et al.
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