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(12) United States Patent (10) Patent No.: US 9,125,936 B2 Meyer Et Al

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(12) United States Patent (10) Patent No.: US 9,125,936 B2 Meyer Et Al US009 125936 B2 (12) United States Patent (10) Patent No.: US 9,125,936 B2 Meyer et al. (45) Date of Patent: Sep. 8, 2015 (54) GINGER EXTRACT FOR THE PROTECTION A61O 15/00 (2013.01); A61 O 19/02 (2013.01); OF STEM CELLS A61 O 19/06 (2013.01); A61 O 19/08 (2013.01) (58) Field of Classification Search (71) Applicant: Symrise AG, Holzminden (DE) None See application file for complete search history. (72) Inventors: Imke Meyer, Bodenwerder (DE); Martina Herrmann, Hameln (DE); (56) References Cited Dominik Stuhlmann, Düsseldorf (DE); Holger Joppe, Dassel (DE) U.S. PATENT DOCUMENTS (73) Assignee: Symrise AG, Holzminden (DE) 2011/02809766,541,046 A1B2 * 11,4/2003 2011 WeiCastor et al. ...................... 424,756 (*) Notice: Subject to any disclaimer, the term of this OTHER PUBLICATIONS patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days. Kawai (Planta Med (1994), vol. 60, pp. 17-20).* http://www.quackwatch.com/01OuackeryRelatedTopics/ (21) Appl. No.: 14/185,157 antiagingpp.html accessed May 20 14. Jolad et al: "Fresh organically grown ginger (Zingiber officinale): (22) Filed: Feb. 20, 2014 composition and effects on LPS-induced PGE2 production.” 9 Phytochemistry vol. 65, pp. 1937-1954 (2004). O O Lee et al: “Protective Effects of Ginger Supercritical Extract against (65) Prior Publication Data Oxidative Damage in L6 Muscle Cells,” J. Korean Soc. Appl. Biol. US 2014/0242020 A1 Aug. 28, 2014 Chem. 54(5), pp. 790-794 (2011). Guahket al: "Zingiber officinale Protects HaCaT cells and C57BL/6 (30) Foreign Application Priority Data Mice from Ultraviolet B-Induced Inflammation.” J. Med. Food 13(3), pp. 673-680 (2010). Feb. 27, 2013 (EP) ..................................... 13156,979 Nakatani et al: "Antioxidants in Ginger Family.” Quality Manage s ment of Nutraceuticals vol. 803, pp. 230-240 (Dec. 17, 2001). (51) Int. Cl Martinez: Stical El Extraction of Nutraceuticals and we Bioactive Compounds.” Taylor & Francis Group, LLC, pp. 337-366 A6K 36/968 (2006.01) (2008). p y p pp A6 IK3I/2 (2006.01) Yoneietal: “Extraction of Ginger Flavor with Liquid or Supercritical A 6LX8/97 (2006.01) Carbon Dioxide.” The Journal of Supercritical Fluids vol. 8, pp. A6 IK 8/35 (2006.01) 156-161 (1995). A61O 19/00 (2006.01) A61O 700 (2006.01) * cited by examiner A61 O 19/08 (2006.01) A61 O5/00 (2006.01) Primary Examiner — Susan Hoffman A61O 5/12 (2006.01) (74) Attorney, Agent, or Firm — Dilworth & Barrese, LLP A61O 15/00 (2006.01) A61 O 19/02 (2006.01) (57) ABSTRACT A61 O 19/06 (2006.01) Ginger extract compositions containing 25 to 30% b.w. 6 (52) U.S. Cl. gingerol, 5 to 10% b.w. 8-gingerol, 5 to 10% b.w. 10 CPC ............... A6 IK36/9068 (2013.01); A6 IK 8/35 gingerol, 1.5 to 4% b.w. 6-shogaol, 0.3 to 1.3% b.W. 8 (2013.01); A61K 8/97 (2013.01); A61 K3I/12 shogaol, 0.03 to 1% b.w. 10-shogaol and 0.01 to 1% b.w. (2013.01); A61O 700 (2013.01); A61O 19/00 Zingerone, with the amount of gingerols totaling 35 to 50% (2013.01); A61 K 2236/37 (2013.01); A61 K b.w.. and the amount of shogaols totaling 1.5 to 6% b.w. 2236/39 (2013.01); A61 K 2800/75 (2013.01); A61O5/006 (2013.01); A61 O 5/12 (2013.01); 15 Claims, 1 Drawing Sheet U.S. Patent Sep. 8, 2015 US 9,125,936 B2 DAD1E, Sig=280.8Ref=550, 100 (SCREENBIO911A2D) mAU 400 300 200 i s 100 US 9,125,936 B2 1. 2 GNGER EXTRACT FOR THE PROTECTION feeling older, weaker and less attractive (Pickard-Holley, OF STEM CELLS Sem. Oncol. Nurs. 1995, 11, 235-238). Agents which are able to stimulate hair growth by prolong FIELD OF INVENTION ing the phase of production of hair material and/or shortening the resting phase of hair follicles as well as to slow down or The present invention belongs to the area of cosmetics and reduce hair loss are known as a cure for alopecia. Examples refers to new ginger extracts in particular useful for skin and for agents stimulating hair growth by altering the hair follicle hair care products. cycle are e.g. drugs; including Minoxidil (Rogaine), Finas teride (Propecia) and Dutasteride (Avodart) are approved STATE OF THE ART 10 treatments for hair loss. However, they require medical pre Scription, and are active only on a certain percentage of the The stem cells, which are located near the hair follicles, are population. Moreover, Some of these drugs are not permitted responsible for the gradually slowing down of the skin to be used by females because of hormonal effects. Thus, renewal system with aging. As a consequence the skin com premenopausal women should not take Finesteride due to the plexion changes from a luminous shine to a dull appearance, 15 risk of abnormalities in male fetus when becoming pregnant from a smooth to a wrinkled Surface, from dense to thin skin (Krus et al., J. Appl. Cosmetol. 2007, 25, 59-74). (Grove et al., J Gerontol 1983,38(2):137-42). The hair as an Minoxidil is a drug that is effective in inducing hair growth appendage of the skin is also affected by the aging of the stem for a small percentage of patients and will re-grow hair only cells: The hair colour is becoming grey to white, the hair on top of the scalp. Adverse effects when taken orally are structure is changing to a thin and fragile structure, the hair tachycardia, angina pectoris and fluid retention. When renewal is decreasing resulting in hair loss and baldness. It applied topically adverse effects are mainly dermatologic, i.e. took years of research to locate the particular stem cell niches, local irritation, itching, dryness and erythema. to identify mechanism leading to a stem cell fade and to Other medical treatments available to treat hair loss include develop first ideas to protect the maintenance of these pro drastic Surgical techniques such as Scalp reduction, Scalp flaps genitor cells to proliferate and differentiate. 25 or follicular unit transplantation. These Surgeries carry the The hair follicle is a mini-organ which hosts four different risk of complications such as elevation of hairline associated stem cell populations in overlapping niches to keep a homeo with donor region, possibility of necrosis and unnatural Stasis in skin and hair integrity (Hodgkinson et al., Expert Rev appearance of hair growth direction, anesthesia and post-op Med Devices 2009, 6(6): 621-40). To ensure the maintenance care, not to mention high costs. of the stem cell populations the microenvironment of these 30 The alteration of the hair follicle cycle helps to retard the niches is multi-faceted and can change Suddenly due to injury hair loss. But to protect from hair loss, hair thinning, baldness but also progressively with cumulative alterations in conse and alopecia the protection of the stem cell population is a quence of UV irradiation and other external stressors (Fuchs, Sustainable mechanism. The onset of hair loss, hair thinning, Cell StemCell 2009, 4(6): 499-502). baldness and alopecia is delayed when the epithelial stem cell In the hair follicle, epithelial stem cells, in principle mul 35 population maintains the capacity to proliferate and differen tipotent stem cells, are located in the bulge, forming hair tiate, also known as Sternness of the stem cells. follicle, epidermis, sebaceous gland, and apocrine gland An incomplete maintenance of melanocyte stem cells in (Tiede et al., Eur J Cell Biol 2007, 86(7): 355-76). Directly the bulge-Subbulge area was shown to cause physiologic hair adherent to the epithelial stem cell population is the melano greying/canities through the loss of the differentiated progeny cyte stem cell population residing in the hair follicle bulge 40 with aging (Nishimura et al., Science 2005, 307(5710): 720 subbulge area, the lower permanent portion of the hair fol 4). A disturbed homeostasis of the melanocyte stem cell licle, to serve as a melanocyte reservoir for skin and hair population is also known to result in pigmentation disorders pigmentation (Nishimura, Pigment Cell Melanoma Res like vitiligo and leucoderma although the mechanisms are not 2011, 24(3): 401-10). identified in detail. But it was already shown that the repig Keeping the stem cells of the skin, especially the stem cells 45 mentation of skin affected by the hypopigmentation disorder of the bulge and bulge-subbulge area of the hair follicle, in a vitiligo is possible by the transplantation of functional hair healthy status guarantees the maintenance of these stem cell follicle melanocyte stem cells (Vanscheidt etal, Dermatology populations to proliferate and differentiate and by this the 2009; 218(4): 342-3) to the affected skin. maintenance of the skin and hair renewal system. By keeping stem cells in a healthy status and protect them The hair follicle undergoes cyclical bouts of regeneration 50 against intrinsic and extrinsic stress factors, in particular by (anagen), degeneration (catagen), and rest (telogen) phase. protecting them against apoptosis, the skin and hair are pro The epithelial stem cell population in the bulge is synchro tected against aging and the hair against loss and greying. nized with these phases forming the hair itself and the follicle Therefore, the object of the present invention has been devel channel. By the protection of the epithelial stem cell popula oping a new active that simultaneously protect stem cells in tion the homeostasis of the hair follicle is given and aging 55 particular against damaging by UV radiation, and is useful for phenomenons like hair loss, hair thinning, baldness and fighting the ageing of skin and hair, in particular against skin alopecia are prevented.
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