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(12) United States Patent (10) Patent No.: US 9,526,718 B2 Lee Et Al

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(12) United States Patent (10) Patent No.: US 9,526,718 B2 Lee Et Al USO09526718B2 (12) United States Patent (10) Patent No.: US 9,526,718 B2 Lee et al. (45) Date of Patent: Dec. 27, 2016 (54) COMBINATION OF EFFECTIVE (56) References Cited SUBSTANCES CAUSING SYNERGISTC EFFECTS OF MULTIPLE TARGETING AND U.S. PATENT DOCUMENTS USE THEREOF 2003/0235589 A1* 12/2003 Demopulos .......... A61K9/0019 424,178.1 (75) Inventors: Doo Hyun Lee, Seoul (KR); Sunyoung 2007/O123544 A1* 5/2007 Plourde et al. ............ 514,2611 Cho, Gyeonggi-do (KR) 2008/0242682 A1 10/2008 Hirai et al. 2010/0311674 A1 12/2010 Zhang 2011/O152205 A1* 6/2011 Liang ................... A61K 31,352 (73) Assignee: VIVOZON, INC., Seoul (KR) 514, 23 (*) Notice: Subject to any disclaimer, the term of this FOREIGN PATENT DOCUMENTS patent is extended or adjusted under 35 CN 101721589 A * 6, 2010 U.S.C. 154(b) by 277 days. JP 2005-526O79. A 9, 2005 JP 2008-531714 A 8, 2008 (21) Appl. No.: 14/128,616 KR 10-2007-0079497 A 7/2007 KR 10-2007-0085973 A 8, 2007 KR 10-2009-01-13462 A 2, 2009 (22) PCT Filed: Jun. 28, 2012 KR 10-2010-00091206. A 8, 2010 WO O3O77897 A1 9, 2003 (86). PCT No.: PCT/KR2O12/OOS145 WO 2006096434 A2 9, 2006 S 371 (c)(1), (2), (4) Date: Jan. 16, 2014 OTHER PUBLICATIONS Houghton et al., a GlyT2 inhibitor, Org 25543, reduces mechanical (87) PCT Pub. No.: WO2013/002584 allodynia in neuropathic rats. Society for Neuroscience Abstracts, PCT Pub. Date: Jan. 3, 2013 (2001) vol. 27, No. 1, pp. 741.* Baek, N., et al., “Effects of Several Medicinal Plants on the Activity (65) Prior Publication Data of GABA-metabolizing Enzymes”, “Kor. J. Pharmacogn.”. 2000, pp. 23-27, vol. 31, No. 1. US 2015/O29O181 A1 Oct. 15, 2015 Baik, E., et al., “Peripheral norepinephrine exacerbates neuritis induced hyperalgesia”, “Journal of Pain', 2003, pp. 212-221 (Eng (30) Foreign Application Priority Data lish Abstract), vol. 4. No. 4. Cavadas, C., et al., “In vitro study on the interaction of Valeriana Jun. 28, 2011 (KR) ........................ 10-2011-0063289 officinalis L. extracts and their amino acids on GABAA receptor in rat brain”, “Arzneimittelforschung'. Jul. 1995, pp. 753-755 (Eng lish Abstract), vol. 45, No. 7. (51) Int. Cl. Chairungsrillerd, N., et al., “Gamma-mangostin, a novel type of A6 IK 36/00 (2006.01) 5-hydroxytryptamine 2A receptor antagonist'. "Naunyn A6 IK 3/445 (2006.01) Schmiedebergs Arch Pharmacol', Jan. 1998, pp. 25-31 (English A61O 19/00 (2006.01) Abstract), vol. 357, No. 1. A6 IK 45/06 (2006.01) (Continued) A6 IK 8/4I (2006.01) A6 IK 8/49 (2006.01) A6 IK3I/I66 (2006.01) Primary Examiner — Qiuwen Mi A6 IK3I/98 (2006.01) (74) Attorney, Agent, or Firm — Hultquist, PLLC; Steven A 6LX 3L/505 (2006.01) J. Hultquist A6 IK 36/884 (2006.01) A6 IK 36/38 (2006.01) A6 IK 36/69 (2006.01) (57) ABSTRACT A6 IK 36/744 (2006.01) Disclosed are a combination of active components inducing A6 IK 36/40 (2006.01) synergistic effects of multi-targeting and a use thereof. More (52) U.S. Cl. particularly, disclosed are a functional food composition, a CPC .............. A6 IK3I/445 (2013.01); A23L 33/10 cosmetic composition, a pain-suppressive composition, and (2016.08); A61K 8/41 (2013.01); A61K 8/4953 a composition for treatment or prevention of pruritus or (2013.01); A61K 31/166 (2013.01); A61 K atopic dermatitis, which comprise as active components, two 31/198 (2013.01); A61K 3 1/505 (2013.01); or more components selected from a group consisting of (a) A61K 36/38 (2013.01); A61K 36/40 (2013.01); a 5-hydroxytryptamine subtype 2 (5-HT2) receptor antago A61K 36/69 (2013.01); A61K 36/744 nist; (b) a P2X receptor antagonist, and (c) any one of a (2013.01); A61K 36/884 (2013.01); A61 K glycine receptor agonist, a glycine transporter (GlyT) 45/06 (2013.01); A61O 19/00 (2013.01); A61 K antagonist, a gamma-aminobutyric acid (GABA) receptor 2800/10 (2013.01) agonist, and a GABA transporter 1 (GAT1) antagonist. (58) Field of Classification Search None See application file for complete search history. 4 Claims, 5 Drawing Sheets US 9,526,718 B2 Page 2 (56) References Cited Relevant Receptors in the Rat Bladder”, “Yakugaku Zasshi'. May 14, 2009, pp.957-964, vol. 129, No. 8. Jung, J., et al., “The Anxiolytic-like Effects of Scutellaria OTHER PUBLICATIONS baicalensis. Using Elevated Plus-Maze in Rats”, “Kor. J. Pharmacogn.”. 2004, pp. 22-27, vol. 35. No. 1. Chaplan, S., et al., “Quantitative assessment of tactile allodynia in Kim, S., et al., “An experimental model for peripheral neuropathy the rat paw”, “Journal of Neuroscience Methods”, 1994, pp.55-63, produced by segmental spinal nerve ligation in the rat”. “Pain'. Sep. vol. 53. 1992, pp. 355-363 (Abstract), vol. 50, No. 3. Cho, H., et al., “Inhibitory Effects of Extracts from Traditional Kim, M., et al., “Functional and Chemical Composition of Herbal Drugs on 5-Hydroxytryptamine Uptake in Primary Cultured Hwanggumkong, Yakong, and Huktae'. “Korean J. Food Cookery Rat Brainstem Neurons”, “Kor. J. Pharmacogn”, 1995, pp. 349 354, vol. 26, No. 4. Sci., Dec. 2005, pp. 844-850, vol. 21, No. 6. Choe, J., et al., “The Chemical Composition of Barley and Wheat Kim, W., et al., “Anxiolytic-like effects of extracts from Albizzia Varieties”, “J. Korean Soc. Food. Sci. Nutr.”, Feb. 2005, pp. julibrissin bark in the elevated plus-maze in rats”, “Life Sciences'. 223-229, vol. 34, No. 2. 2004, pp. 2787-2795, vol. 75. Choi, J., et al., “Effects of Silk Fibroin Powder on Lipofuscin, Lee, J., et al., “Comparison of Nelumbinis Semen Extract with Acetylcholine and Its Related Enzyme Activities in Brain of SD Hypericum Perforatum and Fluoxetine in Animal Model of Depres Rats”, “Korean J. Seric. Sci.”, 2000, pp. 120-125, vol. 42, No. 2. sion”, “Korean J. Oriental Physiology and Pathology', 2006, pp. Chueh, F., et al., “Hypotensive and Bradycardic Effects of dil 830-843, vol. 20, No. 4. Tetrahydropalmatine Mediated by Decrease in Hypothalamic Sero Lee, K., et al., “Studies on Industrial Utilization of Silk Protein', tonin Release in the Rat”, “Jpn. J. Pharmacol.”. 1995, pp. 177-180, “Kor. J. Food Sci. Ind., 2003, pp. 25-37 (Only p. 1 Available), vol. vol. 69. 36, No. 3. Chung, I., et al., “Behavioural pharmacology of polygalasaponins Moon, J., et al., “Nutrient Composition and Physicochemical Prop indicates potential antipsychotic efficacy”. “Pharmacology, Bio erties of Korean Taro Flours According to Cultivars”, “Korean J. chemistry and Behavior', 2002, pp. 191-195, vol. 71. Food Sci. Technol”, Oct. 2010, pp. 613-619, vol. 42, No. 5. Dixon, W., “Efficient Analysis of Experimental Observations'. Purves, D., et al., “GABA and Glycine”, “Neuroscience 2nd Edi “Ann. Rev. Pharmacol. Toxicol.”. 1980, pp. 441-462, vol. 20. tion', 2001, p. 1, (accessed via http://www.ncbi.nlm.nih.gov/books/ Huang, N., et al., “Gastrodia elata prevents rat pheochromocytoma NBK11084), Publisher: Sinauer Associates, Published in: cells from serum-deprived apoptosis: the role of the MAPK family”. Sunderland, MA. “Life Sciences”, 2004, pp. 1649-1657, vol. 75. Xu, X., et al., “Protective Effects of Gastrodin on Hypoxia-Induced Hwang, K., et al., “Screening of Inhibitory Activity of Edible Toxicity in Primary Cultures of Rat Cortical Neurons”, “Planta Mushrooms on the Monoamine Oxidase', 'Korean J. Food Sci. Med”, Jun. 22, 2007, pp. 650-654, vol. 73. Technol.”, 1997, pp. 156-160, vol. 29, No. 1. Yu, H. et al., “Involvement of 5-HT1A and GABAA receptors in the Hwang, J., et al., “Survey for Amino Acid of Medicinal Herbs”. anxiolytic-like effects of Cinnamomum cassia in mice”, “Pharma “Korean Food Sci. Technol.”, 1998, pp. 35-41, vol. 30, No. 1. cology, Biochemistry and Behavior', 2007, pp. 164-170, vol. 87. Hwang, K., et al., “Inhibitory Activity of the Fruit Extract of Mingorance-Le Meur, A., et al., “Reversible inhibition of the Gardenia jasminoides on Monoamine Oxidase”, “Kor. J. glycine transporter GlyT2 circumvents acute toxicity while preserv Pharmacogn.”. 2007, pp. 108-112, vol. 38, No. 2. ing efficacy in the treatment of pain”, “British Joumal of Pharma Imamura, T., et al., “An Extract (THC-002) of Ba-Wei-Die-Huang cology”, Nov. 2013, pp. 1053-1063, vol. 170, No. 5. Wan Inhibits Expression of Tachykinins, and P2X3 and TRPV1 Sang, M., et al., “Foundation review: A Series of case studies: Receptors, and Inhibits ATP-Induced Detrusor Overactivity in practical methodology for identifying antinociceptive multi-target Spontaneously Hypertensive Rats”, “Neurourology and Urodynam drugs”, “Drug Discovery Today'. May 2012, pp. 425-434, vol. 17. ics”, 2009, pp. 529-534, vol. 28. No. 9/10. Ito, Y, et al., “Pharmacological Effects of Hachi-mi-jio-gan Extract (Harncare) on the Contractle Response and on Pharmacologically * cited by examiner U.S. Patent Dec. 27, 2016 Sheet 1 of 5 US 9,526,718 B2 FIG & is 8:3 is 53 milies :::: a cais: : ::::::::::: aaaaaaaaaaaaaaaaaaaaa-aaaaaaaaaaaaaaaaaaaaaaaaaaaa-aaaaaaaaaaaaaaaaaaaaa s U.S. Patent Dec. 27, 2016 Sheet S of 5 US 9,526,718 B2 FG 6 ) : 8x8 x 8xxxx x8xxx xxx: x: 88 8: : Weice - Il of magstee (=3) + 1 g of Palmihag Pills 28 8 x x xxxx xxxxx xxxxx is: Wehicle 0.5g of Palmijiwhang Pills 1 g of Palmijiwhang Pills (-4) (=) =4) US 9,526,718 B2 1. 2 COMBINATION OF EFFECTIVE vention, improvement in atopic dermatitis, skin health, Scalp SUBSTANCES CAUSING SYNERGISTC health, pain control, refreshment, and the like. In addition to EFFECTS OF MULTIPLE TARGETING AND Such functional foods, cosmetic compositions have been USE THEREOF continuously researched and developed to achieve an aes thetic purpose, a therapeutic purpose, and a preventive CROSS-REFERENCE TO RELATED purpose in the fields of skin whitening, antiwrinkle, skin APPLICATIONS elasticity, hair, and Scalp.
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