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

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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. wrinkling, hair-greying, pigment disorders, hair loss and Genetic disposition as well as the natural aging process inflammations. and/or disease contribute to hair loss and slower hair growth in both males and females. Approximately 50% of the popu 60 DESCRIPTION OF THE INVENTION lation displays this trait to some degree by the age of 50. where thinning of the hair can begin between 12 and 40 years Object of the present invention is a new ginger extract, of age independent of gender (Otberg et al., Endocrinol comprising Metab Clin North Am. 2007, 36(2),379-398 and Price, Inves (a) 25 to 30% b.w. I6-gingerol tig Dermatol Symp Proc. 2003, 8 (1), 24-27). Studies reveal 65 (b) 5 to 10% b.w. 8-gingerol psychosocial impact with hair loss to include body image (c) 5 to 10% b.w. 10-gingerol dissatisfaction associated with negative stereotypes such as (d) 1.5 to 4% b.w. 6-shogaol US 9,125,936 B2 3 4 (e) 0.3 to 1.3% b.w. 8-shogaol; 102451 128 A1 suggests a shampoo claimed to prevent hair (f) 0.03 to 1 b.w. 10-shogaol; loss contains 5% ginger juice. JP 63 091315 A1 describes (g) 0.001 to 1% b.w. Zingerone, microcirculation enhancing ginger juice in shampoo forma on condition that the amount of gingerols Sums up to 35 to tions for hair growth stimulation. EP 1281402 B1 (Kao) 50% b.w.. and the amount of shogaols sums up to 1.5 to 6% refers to a ginger extract Substantially free of gingerols for b.w. hair growth inhibition. Another object of the present invention is directed to a Ginger oil was used as a Soothing, relaxing or warming ginger extract of the aforesaid composition, obtainable in that agent in cosmetic formulations in WO 2009 087578 A1 (Foa driedginger leaves or roots are subjected to solvent extraction mix). But the document did not disclose the composition of or supercritical extraction with carbon dioxide. 10 the ginger oil. The essential oil of ginger is known for a strong In a preferred embodiment the ginger extract shows a total pungent Smell and taste due to the Volatile constituents and is content of pungent components (gingerols--shogaols + not comparable to the gingerpungent extract according to the Zingerones) of about 42 to about 50% b.w.. preferably about present invention. 43 to 47% b.w.. and a content of essential oil of less than about The isolation of the pungent components of ginger is 5% b.w.. preferably less than about 2.5% b.w. 15 described in different documents. Ficker et al. (Phytotherapy Surprisingly the ginger (Zingiber officinale) root extract Research (2003), 17(8), 897-902) evaluated the anti-fungal characterized by a high content of pungent components activity of ginger constituents. according to the present invention is capable to protect stem The evaluation of anti-inflammatory activity of pungent cells, more particular stem cells of the hair follicle stem cell components of ginger was given in different documents, inter niche against UVB irradiation and maintain their activity. The alia by Lantz et al. (Phytomedicine (2007), 14(2-3), 123 ginger extract according to the present invention is addition 128). Additionally the anti-tumour activity and proliferation ally a potent anti-oxidant and a potent anti-irritant agent. inhibitory activity on tumour cells were evaluated by different Thus, the ginger extract according to the present invention is groups, interalia by Sang et al. (Journal of Agricultural and a protector against aging, pigmentation disorders, hair grey Food Chemistry (2009), 57(22), 10645-10650). ing and hair loss and thus an agent capable to Support well 25 In CN 1840162 A1 aginger root CO extract is described aging of skin and hair. without specifying the content of pungent components like gingerols and shogaols. The extract is disclosed as an anti BRIEF DESCRIPTION OF THE DRAWING inflammatory extract. Application examples are tablets, pills and capsules for oral consumption. Examples for topical The present invention will be described in greater detail 30 application on skin are not described. with reference to the accompanying drawing in which FIG. 1 Extraction illustrates an HPLC chromatogram obtained for a ginger The ginger extract according to the invention is preferably extract according to the present invention (ginger extract 30 extracted of the dried ginger (Zingiber officinalis) root (rhi mg/10 ml EtOH, detected at 280 nm) with peak at 27.1 min: Zome). The product is prepared by supercritical fluid extrac 6-Gingerol, peak at 33.4 min: 8-Gingerol, peak at 34.5 min: 35 tion with natural carbon dioxide or a solvent mixture of com 6-Shogaol, peak at 39.0 min: 10-Gingerol and peak at 43.0 parable polarity. Due to a fractional supercritical fluid min: 12-Gingerol. extraction the pungent components of ginger are enriched. Another object of the present invention refers to a process DESCRIPTION OF THE PREFERRED for obtaining the new ginger extract, wherein EMBODIMENTS 40 (a) ginger roots are frozen at about -10 to about -25°C., (b) the frozen roots are shredded, cut and dried at about 20 to Ginger Extracts about 50° C. for about 10 to about 30 hours, Ginger root extracts with a high content of pungent com (c) the dried roots are subjected to supercritical extraction ponents are well-known for the flavouring of food and bev with carbon dioxide at about 25 to about 90° C. and about erages. The characterization of ginger root extracts by HPLC, 45 220 to about 370 bar for up to 10 hours; and GC and other analytical methods is well-described. The quan (d) the extraction product obtained after about 3 hours is tification of pungent components like gingerols, shogaols and collected while the forerun taken from the first three hours Zingerone is good laboratory practice. But ginger extracts is dismissed. characterized by a high content of pungent components of More particular ginger root is frozen at about -15 to about 42-50% b.w.. have not been described for cosmetic applica 50 -20°C. The frozenginger is shredded and cut. Afterwards the tions before. material is dried at about 30 to about 40° C. for about 15 to The water and/or ethanol and/or waterlethanol extracts of about 25 hours using a continuous flow dryer. The Supercriti ginger root of unknown composition are described as anti cal fluid extraction is performed with carbon dioxide at about oxidants and anti-aging agents and are often disclosed as the 35 to about 50° C. and about 250 to about 350 bar for up to 10, preferred extracts for these applications. The use of these 55 preferably up to 7 hours. The flow rate is within the range of extracts is described inter alia in JP 2009 073777 A1 for the about 10 to about 20 kg CO/hkg raw material. The extract improvement of wrinkles, in JP 2000319189 A1 as elastase of the first fraction in the first 2 to 3 hours is dominated by inhibitors, by Fujimura et al. (Fragrance Journal (2002), essential oil after the de-pressurizing process. The extract of 30(6), 38-42) for wrinkle improvement by inhibition of the second fraction taken from 3 up to 7 hours from the elastase activity. In JP 2007008847 the claimed extract was 60 starting is the extract according to the present invention after prepared with 20% ethanol resulting in the concentration of the de-pressurizing process. fructosyl dipeptides as active principles. Pungent components of ginger extract are in means of the For the application to hair and scalp ginger tincture, ginger present invention gingerols, shogaols, Zingerone, gingerdi juice and the above mentioned water and/or ethanol and/or ols, dehydrogingerdiones and paradols. water/ethanol extracts of ginger root are well-known. As 65 The extract is characterized by about 42 to about 50% total activities for these extracts on hair and scalp inter alia pungent compounds mainly gingerols and shogaols with the enhanced microcirculation is described. For example. CN proviso that extract comprises less than 6% shogaols. The US 9,125,936 B2 5 6 content of Zingerone in the ginger extract according to the A. Surfactants present invention is lower than 1%. Other preferred auxiliaries and additives are anionic and/or The advantage of the ginger extract according to the amphoteric or Zwitterionic Surfactants. Typical examples of present invention is the low content of essential oil with less anionic Surfactants are soaps, alkyl benzenesulfonates, than about 5% b.w.. more preferable less than about 2.5%b.w. alkanesulfonates, olefin Sulfonates, alkylether Sulfonates, Several components of the essential oil of ginger are known glycerol ether sulfonates, methyl ester sulfonates, sulfofatty skin sensitizers, by way of example citral, citronellol, acids, alkyl Sulfates, fatty alcohol ether Sulfates, glycerol eugenol, geraniol, isoeugenol, limonene and linalool. By way ether sulfates, fatty acid ether sulfates, hydroxy mixed ether of example the skin sensitizers citral, Linalool, Citronellol Sulfates, monoglyceride (ether) sulfates, fatty acid amide 10 (ether) Sulfates, mono- and dialkyl SulfoSuccinates, mono and d-Limonene are limited due to the production procedure and dialkyl SulfoSuccinamates, Sulfotriglycerides, amide to a concentration of about 0.7% b.w..., 0.2% b.w..., 0.07% b.w. Soaps, ether carboxylic acids and salts thereof, fatty acid and 0.3%, b.w. respectively. isethionates, fatty acid sarcosinates, fatty acid taurides, Due to the low content of essential oil the ginger extract N-acylamino acids Such as, for example, acyl lactylates, acyl according to the present invention has no to negligible odour 15 tartrates, acylglutamates and acyl aspartates, alkyl oligoglu when incorporated in a cosmetic formulation in concentra coside Sulfates, protein fatty acid condensates (particularly tions sufficient to protect stem cells in the skin. wheat-based vegetable products) and alkyl(ether) phos The ginger extract according to the present invention is a phates. If the anionic Surfactants contain polyglycol ether brown clear oily liquid with negligible pungent Smell and chains, they may have a conventional homolog distribution taSte. although they preferably have a narrow-range homolog dis By the extraction procedure and the resulting enrichment tribution. Typical examples of amphoteric or Zwitterionic of pungent components a high content of lipophilic compo Surfactants are alkyl-betaines, alkylamidobetaines, amino nents is combined with a low content of essential oil. By this propionates, aminoglycinates, imidazolinium betaines and the ginger extract according to the present invention is ben Sulfobetaines. The Surfactants mentioned are all known com eficial with regard to the potent stem cell protection properties 25 pounds. Information on their structure and production can be and also with regard to negligible Smell and with regard to a found in relevant synoptic works, cf. for example J. Falbe low sensitizing potential. (ed.), “Surfactants in Consumer Products”, Springer Verlag, Cosmetic Compositions Berlin, 1987, pages 54 to 124 or J. Falbe (ed.), “Katalysa Another embodiment of the present invention refers to a toren, Tenside and Mineralóladditive (Catalysts, Surfactants cosmetic composition comprising the new ginger extract, 30 and Mineral Oil Additives)’. Thieme Verlag, Stuttgart, 1978, containing the extract in an amount of from about 0.01 to pages 123-217. The percentage content of Surfactants in the about 1, preferably from about 0.1 to about 0.5% b.w.— preparations may be from 0.1 to 10% by weight and is pref calculated on the total composition. erably from 0.5 to 5% by weight, based on the preparation. The preparations according to the invention may contain B. Oil Bodies abrasives, antiacne agents, agents against ageing of the skin, 35 Suitable oil bodies, which form constituents of the O/W anticellulitis agents, antidandruff agents, antiinflammatory emulsions, are, for example, Guerbet alcohols based on fatty agents, irritation-preventing agents, irritation-inhibiting alcohols having 6 to 18, preferably 8 to 10, carbon atoms, agents, antioxidants, astringents, perspiration-inhibiting esters of linear C-C-fatty acids with linear or branched agents, antiseptic agents, antistatics, binders, buffers, carrier C-C-fatty alcohols or esters of branched C-C-carboxy materials, chelating agents, cell stimulants, cleansing agents, 40 lic acids with linear or branched C-C-fatty alcohols, such care agents, depilatory agents, Surface-active Substances, as, for example, myristyl myristate, myristyl palmitate, myri deodorizing agents, antiperspirants, softeners, emulsifiers, styl Stearate, myristyl isoStearate, myristyl oleate, myristyl enzymes, essential oils, fibres, film-forming agents, fixatives, behenate, myristyl erucate, cetyl myristate, cetyl palmitate, foam-forming agents, foam stabilizers, Substances for pre cetyl Stearate, cetyl isostearate, cetyl oleate, cetyl behenate, Venting foaming, foam boosters, gelling agents, gel-forming 45 cetyl erucate, Stearyl myristate, Stearyl palmitate, Stearyl agents, hair care agents, hair-setting agents, hair-straighten Stearate, Stearyl isostearate, Stearyl oleate, Stearyl behenate, ing agents, moisture-donating agents, moisturizing Sub Stearyl erucate, isostearyl myristate, isoStearyl palmitate, stances, moisture-retaining Substances, bleaching agents, isostearyl Stearate, isostearyl isostearate, isostearyl oleate, strengthening agents, stain-removing agents, optically isostearyl behenate, isostearyl oleate, oleyl myristate, oleyl brightening agents, impregnating agents, dirt-repellent 50 palmitate, oleyl Stearate, oleyl isostearate, oleyl oleate, oleyl agents, friction-reducing agents, lubricants, moisturizing behenate, oleyl erucate, behenyl myristate, behenyl palmi creams, ointments, opacifying agents, plasticizing agents, tate, behenyl stearate, behenyl isostearate, behenyl oleate, covering agents, polish, gloss agents, polymers, powders, behenyl behenate, behenyl erucate, erucyl myristate, erucyl proteins, re-oiling agents, abrading agents, silicones, skin palmitate, erucyl Stearate, erucyl isostearate, erucyl oleate, Soothing agents, skin-cleansing agents, skin care agents, 55 erucyl behenate and erucylerucate. Also suitable are esters of skin-healing agents, skin-lightening agents, skin-protecting linear C-C-fatty acids with branched alcohols, in particular agents, skin-Softening agents, cooling agents, skin-cooling 2-ethylhexanol, esters of Cs-Cs-alkylhydroxy carboxylic agents, warming agents, skin-warming agents, stabilizers, acids with linear or branched C-C-fatty alcohols, in par UV-absorbing agents, UV filters, detergents, fabric condi ticular Dioctyl Malate, esters of linear and/or branched fatty tioning agents, Suspending agents, skin-tanning agents, thick 60 acids with polyhydric alcohols (such as, for example, propy eners, vitamins, oils, waxes, fats, phospholipids, Saturated lene glycol, dimerdiolor trimertriol) and/or Guerbet alcohols, fatty acids, mono- or polyunsaturated fatty acids, C-hydroxy triglycerides based on Co-Co-fatty acids, liquid mono-fcli-f acids, polyhydroxy-fatty acids, liquefiers, dyestuffs, colour triglyceride mixtures based on C-Cls-fatty acids, esters of protecting agents, pigments, anticorrosives, aromas, flavour C-C-fatty alcohols and/or Guerbet alcohols with aromatic ing Substances, odoriferous Substances, polyols, Surfactants, 65 carboxylic acids, in particular benzoic acid, esters of C-C2 electrolytes, organic solvents or silicone derivatives and the dicarboxylic acids with linear or branched alcohols having 1 like as additional auxiliaries and additives. to 22 carbonatoms or polyols having 2 to 10 carbonatoms and US 9,125,936 B2 7 8 2 to 6 hydroxyl groups, vegetable oils, branched primary (i) Partial glycerides. Typical examples of suitable partial alcohols, Substituted cyclohexanes, linear and branched glycerides are hydroxy Stearic acid monoglyceride, C-C-fatty alcohol carbonates, such as, for example, Dica hydroxy Stearic acid diglyceride, isostearic acid monoglyc prylyl Carbonate (Cetiol RCC), Guerbet carbonates, based eride, isostearic acid diglyceride, oleic acid monoglycer on fatty alcohols having 6 to 18, preferably 8 to 10, carbon 5 ide, oleic acid diglyceride, ricinoleic acid monoglyceride, atoms, esters of benzoic acid with linear and/or branched ricinoleic acid diglyceride, linoleic acid monoglyceride, C-C-alcohols (e.g. Finsolv(R) TN), linear or branched, linoleic acid diglyceride, linolenic acid monoglyceride, symmetrical or asymmetrical dialkyl ethers having 6 to 22 linolenic acid diglyceride, erucic acid monoglyceride, eru carbon atoms per alkyl group. Such as, for example, dicapry cic acid diglyceride, tartaric acid monoglyceride, tartaric 10 acid diglyceride, citric acid monoglyceride, citric acid dig lyl ether (Cetiol ROE), ring-opening products of epoxidized lyceride, malic acid monoglyceride, malic acid diglyceride fatty acid esters with polyols, silicone oils (cyclomethicones, and technical mixtures thereof which may still contain silicone methicone grades, etc.) and/or aliphatic or naph Small quantities of triglyceride from the production pro thenic hydrocarbons, such as, for example, squalane, cess. Addition products of 1 to 30 and preferably 5 to 10 squalene or dialkylcyclohexanes. 15 mol ethylene oxide onto the partial glycerides mentioned C. Emulsifiers are also suitable. Other Surfactants may also be added to the preparations as (ii) Sorbitan esters. Suitable sorbitan esters are sorbitan emulsifiers, including for example: monoisoStearate, Sorbitan sesquisostearate, Sorbitan dii products of the addition of 2 to 30 mol ethylene oxide SoStearate, Sorbitan trisoStearate, Sorbitan monooleate, and/or 0 to 5 mol propylene oxide onto linear Cs fatty Sorbitan sesquioleate, Sorbitan dioleate, Sorbitan trioleate, alcohols, onto C fatty acids and onto alkyl phenols Sorbitan monoerucate, Sorbitan sesquierucate, Sorbitan containing 8 to 15 carbon atoms in the alkyl group; dierucate, Sorbitan trierucate, Sorbitan monoricinoleate, Cs fatty acid monoesters and diesters of addition prod Sorbitan sesquiricinoleate, Sorbitan diricinoleate, Sorbitan ucts of 1 to 30 mol ethylene oxide onto glycerol: triricinoleate, Sorbitan monohydroxy Stearate, Sorbitan Ses glycerol mono- and diesters and Sorbitan mono- and 25 quihydroxy Stearate, Sorbitan dihydroxyStearate, Sorbitan diesters of saturated and unsaturated fatty acids contain trihydroxy Stearate, Sorbitan monotartrate, Sorbitan Ses ing 6 to 22 carbon atoms and ethylene oxide addition quitartrate, Sorbitan ditartrate, Sorbitan tritaritrate, Sorbitan products thereof; monocitrate, Sorbitan sesquicitrate, Sorbitan dicitrate, Sor addition products of 15 to 60 mol ethylene oxide onto bitan tricitrate, Sorbitan monomaleate, Sorbitan Ses castor oil and/or hydrogenated castor oil; 30 quimaleate, Sorbitan dimaleate, Sorbitan trimaleate and polyolesters and, in particular, polyglycerol esters such as, technical mixtures thereof. Addition products of 1 to 30 for example, polyglycerol polyricinoleate, polyglycerol and preferably 5 to 10 molethylene oxide onto the sorbitan poly-12-hydroxyStearate or polyglycerol dimerate isos esters mentioned are also suitable. tearate. Mixtures of compounds from several of these (iii) Polyglycerol esters. Typical examples of Suitable polyg classes are also Suitable; 35 lycerol esters are Polyglyceryl-2 Dipolyhydroxystearate addition products of 2 to 15 molethylene oxide onto castor (Dehymuls(R PGPH), Polyglycerin-3-Diisostearate oil and/or hydrogenated castor oil; (Lameform R) TGI), Polyglyceryl-4 Isostearate (Isolan R. partial esters based on linear, branched, unsaturated or GI 34), Polyglyceryl-3 Oleate, Diisostearoyl Polyglyc Saturated C2 fatty acids, ricinoleic acid and 12-hy eryl-3 Diisostearate (Isolan R. PDI), Polyglyceryl-3 Meth droxyStearic acid and glycerol, polyglycerol, pen 40 ylglucose Distearate (Tego Care R 450), Polyglyceryl-3 taerythritol, -dipentaerythritol, Sugar alcohols (for Beeswax (Cera BellinaR), Polyglyceryl-4 Caprate (Polyg example Sorbitol), alkyl glucosides (for example methyl lycerol Caprate T2010/90), Polyglyceryl-3 Cetyl Ether glucoside, butyl glucoside, lauryl glucoside) and poly (Chimexane(R) NL), Polyglyceryl-3 Distearate (Cremo glucosides (for example cellulose); phor RGS 32) and Polyglyceryl Polyricinoleate (AdmulR) mono-, di and trialkyl phosphates and mono-, di- and/or 45 WOL 1403), Polyglyceryl Dimerate Isostearate and mix tri-PEG-alkyl phosphates and salts thereof; tures thereof. Examples of other suitable polyolesters are wool wax alcohols; the mono-, di- and triesters of trimethylol propane or pen polysiloxane/polyalkyl polyether copolymers and corre taerythritol with lauric acid, cocofatty acid, tallow fatty sponding derivatives; acid, palmitic acid, Stearic acid, oleic acid, behenic acid mixed esters of pentaerythritol, fatty acids, citric acid and 50 and the like optionally reacted with 1 to 30 mol ethylene fatty alcohol and/or mixed esters of C-2 fatty acids, oxide. methyl glucose and polyols, preferably glycerol or (iv) Anionic emulsifiers. Typical anionic emulsifiers are ali polyglycerol, phatic C-2 fatty acids, such as palmitic acid, Stearic acid polyalkylene glycols and or behenic acid for example, and C-dicarboxylic acids, glycerol carbonate. 55 Such as azelaic acid or sebacic acid for example. The addition products of ethylene oxide and/or propylene (v) Amphoteric emulsifiers. Other suitable emulsifiers are oxide onto fatty alcohols, fatty acids, alkylphenols, glycerol amphiboteric or Zwitterionic surfactants. Zwitterionic sur mono- and diesters and Sorbitan mono- and diesters of fatty factants are surface-active compounds which contain at acids or onto castor oil are known commercially available least one quaternary ammonium group and at least one products. They are homologue mixtures of which the average 60 carboxylate and one Sulfonate group in the molecule. Par degree of alkoxylation corresponds to the ratio between the ticularly suitable Zwitterionic surfactants are the so-called quantities of ethylene oxide and/or propylene oxide and Sub betaines, such as the N-alkyl-N,N-dimethyl ammonium strate with which the addition reaction is carried out. Cas glycinates, for example cocoalkyl dimethyl ammonium fatty acid monoesters and diesters of addition products of glycinate, N-acylaminopropyl-N,N-dimethyl ammonium ethylene oxide onto glycerol are known as lipid layer enhanc 65 glycinates, for example cocoacylaminopropyl dimethyl ers for cosmetic formulations. The preferred emulsifiers are ammonium glycinate, and 2-alkyl-3-carboxymethyl-3-hy described in more detail as follows: droxyethyl imidazolines containing 8 to 18 carbon atoms US 9,125,936 B2 10 in the alkyl or acyl group and cocoacylaminoethyl example, Jaguar R. CBS, Jaguar R C-17, Jaguar R C-16 of hydroxyethyl carboxymethyl glycinate. The fatty acid Celanese, quaternized ammonium salt polymers such as, for amide derivative known under the CTFA name of Cocami example, Mirapolr A-15, Mirapolr) AD-1, Mirapolr AZ-1 dopropyl Betaine is particularly preferred. Ampholytic sur of Miranol and the various polyguarternium types (for factants are also suitable emulsifiers. Ampholytic Surfac 5 example 6, 7, 32 or 37) which can be found in the market tants are surface-active compounds which, in addition to a under the tradenames Rheocare(R) CC or Ultragel(R) 300. Css alkyl or acyl group, contain at least one free amino Suitable anionic, Zwitterionic, amphoteric and nonionic group and at least one —COOH- or —SOH- group in polymers are, for example, vinyl acetate/crotonic acid the molecule and which are capable of forming inner salts. copolymers, vinyl pyrrolidone/vinyl acrylate copolymers, Examples of suitable ampholytic surfactants are N-alkyl 10 vinyl acetate/butyl maleate/isobornyl acrylate copolymers, glycines, N-alkyl propionic acids, N-alkylaminobutyric methyl vinylether/maleic anhydride copolymers and esters acids, N-alkyliminodipropionic acids, N-hydroxyethyl-N- thereof, uncrosslinked and polyol-crosslinked polyacrylic alkylamidopropyl glycines, N-alkyl taurines, N-alkyl sar acids, acrylamidopropyl trimethylammonium chloride/acry cosines, 2-alkylaminopropionic acids and alkylaminoace late copolymers, octylacrylamide/methyl methacrylate?tert.- tic acids containing around 8 to 18 carbon atoms in the 15 butylaminoethyl methacrylate/2-hydroxypropyl methacry alkyl group. Particularly preferred ampholytic Surfactants late copolymers, polyvinyl pyrrolidone, vinyl pyrrolidone? are N-cocoalkylaminopropionate, cocoacylaminoethyl vinyl acetate copolymers, vinyl pyrrolidone/ aminopropionate and C2s acyl sarcosine. dimethylaminoethyl methacrylate/vinyl caprolactam D. Superfatting Agents and Consistency Factors terpolymers and optionally derivatized cellulose ethers and Superfatting agents may be selected from Such substances silicones. as, for example, lanolin and lecithin and also polyethoxylated G. Pearlising Waxes or acylated lanolin and lecithin derivatives, polyol fatty acid Suitable pearlising waxes are, for example, alkylene glycol esters, monoglycerides andfatty acidalkanolamides, the fatty esters, especially ethylene glycol distearate; fatty acid acid alkanolamides also serving as foam stabilizers. alkanolamides, especially cocofatty acid diethanolamide; The consistency factors mainly used are fatty alcohols or 25 partial glycerides, especially Stearic acid monoglyceride; hydroxyfatty alcohols containing 12 to 22 and preferably 16 esters of polybasic, optionally hydroxy-Substituted carboxy to 18 carbon atoms and also partial glycerides, fatty acids or lic acids with fatty alcohols containing 6 to 22 carbon atoms, hydroxyfatty acids. A combination of these substances with especially long-chain esters of tartaric acid; fatty compounds, alkyl oligoglucosides and/or fatty acid N-methylglucamides Such as for example fatty alcohols, fatty ketones, fatty alde of the same chain length and/or polyglycerol poly-12-hy 30 hydes, fatty ethers and fatty carbonates which contain in all at droxyStearates is preferably used. least 24 carbon atoms, especially laurone and distearylether; E. Thickening Agents and Rheology Additives fatty acids, such as Stearic acid, hydroxystearic acid or Suitable thickeners are polymeric thickeners, such as Aero behenic acid, ring opening products of olefin epoxides con sil.R types (hydrophilic silicas), polysaccharides, more espe taining 12 to 22 carbon atoms with fatty alcohols containing cially Xanthan gum, guar-guar, agar-agar, alginates and 35 12 to 22 carbon atoms and/or polyols containing 2 to 15 tyloses, carboxymethylcellulose and hydroxyethyl cellulose, carbon atoms and 2 to 10 hydroxyl groups and mixtures also relatively high molecular weight polyethylene glycol thereof. monoesters and diesters of fatty acids, polyacrylates (for H. Silicones example Carbopols(R) Goodrich or Synthalens(R) Sigma), Suitable silicone compounds are, for example, dimethyl polyacrylamides, polyvinyl alcohol and polyvinyl pyrroli 40 polysiloxanes, methylphenyl polysiloxanes, cyclic silicones done, Surfactants such as, for example, ethoxylated fatty acid and amino-, fatty acid-, alcohol-, polyether-, epoxy-, fluo glycerides, esters of fatty acids with polyols, for example rine-, glycoside- and/or alkyl-modified silicone compounds pentaerythritol or trimethylol propane, narrow-range fatty which may be both liquid and resin-like at room temperature. alcohol ethoxylates and electrolytes, such as sodium chloride Other suitable silicone compounds are simethicones which and ammonium chloride. 45 are mixtures of dimethicones with an average chain length of F. Polymers 200 to 300 dimethylsiloxane units and hydrogenated sili Suitable cationic polymers are, for example, cationic cel cates. A detailed overview of suitable volatile silicones can be lulose derivatives such as, for example, the quaternized found in Todd et al. in Cosm. Toil. 91, 27 (1976). hydroxyethyl cellulose obtainable from Amerchol under the I. Waxes and Stabilizers name of Polymer JR 400R, cationic starch, copolymers of 50 Besides natural oils used, waxes may also be present in the diallyl ammonium salts and acrylamides, quaternized vinyl preparations, more especially natural waxes such as, for pyrrolidone/vinyl imidazole polymers such as, for example, example, candelilla wax, carnauba wax, Japan wax, espar Luvicquat(R) (BASF), condensation products of polyglycols tograss wax, cork wax, guaruma wax, rice oil Wax, Sugarcane and amines, quaternized collagen polypeptides Such as, for wax, ouricury wax, montan wax, beeswax, shellac wax, sper example, Lauryldimonium Hydroxypropyl Hydrolyzed Col 55 maceti, lanolin (wool wax), uropygial fat, ceresine, oZocerite lagen (Lamequat R. L. Grünau), quaternized wheat polypep (earth wax), petrolatum, paraffin waxes and microwaxes; tides, polyethyleneimine, cationic silicone polymers such as, chemically modified waxes (hard waxes) such as, for for example, amodimethicone, copolymers of adipic acid and example, montan ester waxes, Sasol waxes, hydrogenated dimethylaminohydroxypropyl diethylenetriamine (Cartaret jojoba waxes and synthetic waxes such as, for example, poly ine(R), Sandoz), copolymers of acrylic acid with dimethyl 60 alkylene waxes and polyethylene glycol waxes. diallyl ammonium chloride (MerquatR 550, Chemviron), Metal salts offatty acids such as, for example, magnesium, polyaminopolyamides and crosslinked water-soluble poly aluminium and/or Zinc Stearate or ricinoleate may be used as mers thereof, cationic chitin derivatives such as, for example, stabilizers. quaternized chitosan, optionally in microcrystalline distribu J. Primary Sun Protection Factors tion, condensation products of dihaloalkyls, for example 65 Primary sun protection factors in the context of the inven dibromobutane, with bis-dialkylamines, for example bis tion are, for example, organic Substances (light filters) which dimethylamino-1,3-propane, cationic guar gum Such as, for are liquid or crystalline at room temperature and which are US 9,125,936 B2 11 12 capable of absorbing ultraviolet radiation and of releasing the N-(2 and 4)-2-(oxoborn-3-ylidene)methylbenzyl)acry energy absorbed in the form of longer-wave radiation, for lamide polymer example heat. 4,4'-(6-4-(1,1-dimethyl)aminocarbonyl)phenylamino The formulations according to the invention advanta 1,3,5-triazine-2,4-diyl)diimino-bis-(benzoic acid-2- geously contain at least one UV-A filter and/or at least one ethylhexyl ester) (Uvasorb(R) HEB) UV-B filter and/or abroadband filter and/or at least one inor benzylidene malonate polysiloxane (Parsol(R) SLX) ganic pigment. Formulations according to the invention pref glyceryl ethylhexanoate dimethoxycinnamate erably contain at least one UV-B filter or a broadband filter, dipropylene glycol salicylate more particularly preferably at least one UV-A filter and at tris(2-ethylhexyl)-4,4',4'-(1,3,5-triazine-2,4,6-triyltri 10 imino)tribenzoate (2,4,6-trianilino-(p-carbo-2'-ethyl least one UV-B filter. hexyl-1'-oxy)-1,3,5-triazine) (Uvinul RT150) Preferred cosmetic compositions, preferably topical for Broadband filters which are preferably combined with one mulations according to the present invention comprise one, or more compounds of formula (I) in a preparation according two, three or more sun protection factors selected from the to the present invention are selected from the group consisting group consisting of 4-aminobenzoic acid and derivatives, 15 of salicylic acid derivatives, benzophenone derivatives, diben 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate (Neo Helio Zoylmethane derivatives, diphenyl acrylates, 3-imidazol-4-yl pan R. 303) acrylic acid and esters thereof, benzofuran derivatives, ben ethyl-2-cyano-3,3'-diphenyl acrylate Zylidene malonate derivatives, polymeric UV absorbers con 2-hydroxy-4-methoxybenzophenone (Neo Heliopan R. taining one or more organosilicon radicals, cinnamic acid BB) derivatives, camphor derivatives, trianilino-s-triazine deriva 2-hydroxy-4-methoxybenzophenone-5-Sulfonic acid tives, 2-hydroxyphenylbenzotriazole derivatives, phenylben dihydroxy-4-methoxybenzophenone Zimidazole sulfonic acid derivatives and salts thereof, anthra 2,4-dihydroxybenzophenone nilic acid menthyl esters, benzotriazole derivatives and indole tetrahydroxybenzophenone derivatives. 25 2,2'-dihydroxy-4,4'-dimethoxybenzophenone In addition, it is advantageous to combine compounds of 2-hydroxy-4-n-octoxybenzophenone formula (I) with active ingredients which penetrate into the 2-hydroxy-4-methoxy-4'-methylbenzophenone skin and protect the skin cells from inside against Sunlight Sodium hydroxymethoxybenzophenone Sulfonate induced damage and reduce the level of cutaneous matrix disodium-2,2'-dihydroxy-4,4'-dimethoxy-5,5-disulfoben metalloproteases. Preferred respective ingredients, so called 30 Zophenone arylhydrocarbon receptor antagonists, are described in WO phenol, 2-(2H-benzotriazol-2-yl)-4-methyl-6-(2-methyl-3 2007/128723, incorporated herein by reference. Preferred is (1,3,3,3-tetramethyl-1-(trimethylsilyl)oxy)disiloxya 2-benzylidene-5,6-dimethoxy-3,3-dimethylindan-1-one. nyl) propyl) (Mexoryl(R) XL) The UV filters cited below which can be used within the 2,2'-methylene bis-(6-(2H-benzotriazol-2-yl)-4-1,1,3,3- context of the present invention are preferred but naturally are 35 tetramethylbutyl) phenol) (Tinosorb(RM) not limiting. 2.4-bis-(4-(2-ethylhexyloxy)-2-hydroxyphenyl-1,3,5-tri UV filters which are preferably used are selected from the aZ1 group consisting of 2.4-bis-((4-(2-ethylhexyloxy)-2-hydroxyphenyl]-6-(4- p-aminobenzoic acid methoxyphenyl)-1,3,5-triazine (Tinosorb(RS) p-aminobenzoic acid ethyl ester (25 mol) ethoxylated 40 2.4-bis-(4-(3-sulfonato)-2-hydroxypropyloxy)-2- (INCI name: PEG-25 PABA) hydroxyphenyl]-6-(4-methoxyphenyl)-1,3,5-triazine p-dimethylaminobenzoic acid-2-ethylhexyl ester Sodium salt p-aminobenzoic acid ethyl ester (2 mol) N-propoxylated 2.4-bis-(3-(2-propyloxy)-2-hydroxypropyloxy)-2- p-aminobenzoic acid glycerol ester hydroxyphenyl]-6-(4-methoxyphenyl)-1,3,5-triazine salicylic acid homomethyl ester (homosalates) (Neo Helio 45 2.4-bis-(4-(2-ethylhexyloxy)-2-hydroxyphenyl]-6-4- pan R HMS) (2-methoxyethyl carbonyl)phenylamino-1,3,5-triazine salicylic acid-2-ethylhexyl ester (Neo Heliopan ROS) 2.4-bis-(4-(3-(2-propyloxy)-2-hydroxypropyloxy)-2- triethanolamine Salicylate hydroxyphenyl]-6-4-(2-ethylcarboxyl)pheny 4-isopropylbenzyl salicylate lamino-1,3,5-triazine anthranilic acid menthyl ester (Neo Heliopan R MA) 50 2.4-bis-(4-(2-ethylhexyloxy)-2-hydroxyphenyl]-6-(1- diisopropyl cinnamic acid ethyl ester methylpyrrol-2-yl)-1,3,5-triazine p-methoxycinnamic acid-2-ethylhexyl ester (Neo Helio 2.4-bis-(4-tris-(trimethylsiloxysilylpropyloxy)-2- pan RAV) hydroxyphenyl]-6-(4-methoxyphenyl)-1,3,5-triazine diisopropyl cinnamic acid methyl ester 2.4-bis-(4-(2"-methylpropenyloxy)-2-hydroxyphenyl p-methoxycinnamic acid isoamyl ester (Neo Heliopan RE 55 6-(4-methoxyphenyl)-1,3,5-triazine 1000) 2.4-bis-(4-(1,1,1',3',5',5',5'-heptamethylsiloxy-2"-meth p-methoxycinnamic acid diethanolamine salt ylpropyloxy)-2-hydroxyphenyl]-6-(4-methoxyphe p-methoxycinnamic acid isopropyl ester nyl)-1,3,5-triazine 2-phenylbenzimidazole sulfonic acid and salts (Neo Helio UV-A filters filters which are preferably combined with pan R. Hydro) 60 one or more compounds of formula (I) in a preparation 3-(4-trimethylammonium)benzylidene bornan-2-one according to the present invention are selected from the group methyl sulfate consisting of beta-imidazole-4(5)-acrylic acid (urocanic acid) 4-isopropyl dibenzoyl methane 3-(4'-sulfo)benzylidene bornan-2-one and salts terephthalylidenedibornane sulfonic acid and salts (Mexo 3-(4-methylbenzylidene)-D.L-camphor (Neo Heliopan R. 65 ryl(R) SX) MBC) 4-t-butyl-4'-methoxydibenzoyl methane (avobenzone)/ 3-benzylidene-D.L-camphor (Neo Heliopan R 357) US 9,125,936 B2 13 14 phenylene bis-benzimidazyl tetrasulfonic acid disodium pigment. The preparations may be present here in various salt (Neo Heliopan RAP) forms such as are conventionally used for Sun protection 2,2'-(1,4-phenylene)-bis-(1H-benzimidazole-4,6-disul preparations. Thus, they may be in form of a solution, an fonic acid), monosodium salt emulsion of the water-in-oil type (W/O) or of the oil-in-water 2-(4-diethylamino-2-hydroxybenzoyl)benzoic acid hexyl type (O/W) or a multiple emulsion, for example of the water ester (Uvinul R A Plus) in-oil-in-water type (W/O/W), a gel, a hydrodispersion, a indanylidene compounds in accordance with DE 100 55 Solid stick or else an aerosol. 940 A1 (=WO 2002 038537 A1) Inafurther preferred embodiment a formulation according UV filters which are more preferably combined with one or to the invention contains a total amount of Sunscreen agents, more compounds of formula (I) in a preparation according to 10 i.e. in particular UV filters and/or inorganic pigments (UV the present invention are selected from the group consisting filtering pigments) so that the formulation according to the of invention has a light protection factor of greater than or equal p-aminobenzoic acid to 2 (preferably greater than or equal to 5). Such formulations 3-(4-trimethylammonium)benzylidene bornan-2-one according to the invention are particularly Suitable for pro methyl sulfate 15 tecting the skin and hair. salicylic acid homomethyl ester (Neo Heliopan R HMS) K. Secondary Sun Protection Factors 2-hydroxy-4-methoxybenzophenone (Neo Heliopan R. Besides the groups of primary Sun protection factors men BB) tioned above, secondary Sun protection factors of the antioxi 2-phenylbenzimidazole sulfonic acid (Neo Heliopan R. dant type may also be used. Secondary Sun protection factors Hydro) of the antioxidant type interrupt the photochemical reaction terephthalylidenedibornane sulfonic acid and salts (Mexo chain which is initiated when UV rays penetrate into the skin. ryl(R) SX) Typical examples are amino acids (for example glycine, his 4-tert-butyl-4'-methoxydibenzoyl methane (Neo Helio tidine, tyrosine, tryptophane) and derivatives thereof, imida pan R 357) Zoles (for example urocanic acid) and derivatives thereof, 3-(4'-sulfo)benzylidene bornan-2-one and salts 25 peptides, such as D.L-carnosine, D-carnosine, L-carnosine 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate (Neo Helio and derivatives thereof (for example anserine), carotinoids, pan R. 303) carotenes (for example alpha-carotene, beta-carotene, lyco N-(2 and 4)-2-(oxoborn-3-ylidene)methylbenzyl)acry pene) and derivatives thereof, chlorogenic acid and deriva lamide polymer tives thereof, liponic acid and derivatives thereof (for p-methoxycinnamic acid-2-ethylhexyl ester (Neo Helio 30 example dihydroliponic acid), aurothioglucose, propylthiou pan RAV) racil and other thiols (for example thioredoxine, glutathione, p-aminobenzoic acid ethyl ester (25 mol) ethoxylated cysteine, cystine, cystamine and glycosyl, N-acetyl, methyl, (INCI name: PEG-25 PABA) ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, alpha p-methoxycinnamic acid isoamyl ester (Neo Heliopan R. linoleyl, cholesteryl and glyceryl esters thereof) and their E1000) 35 salts, dilaurylthiodipropionate, distearylthiodipropionate, 2,4,6-trianilino-(p-carbo-2'-ethylhexyl-1'-oxy)-1,3,5-tri thiodipropionic acid and derivatives thereof (esters, ethers, azine (Uvinul RT150) peptides, lipids, nucleotides, nucleosides and salts) and Sul phenol, 2-(2H-benzotriazol-2-yl)-4-methyl-6-(2-methyl-3 foXimine compounds (for example butionine Sulfoximines, (1,3,3,3-tetramethyl-1-(trimethylsilyl)oxy)disiloxya homocysteine Sulfoximine, butionine Sulfones, penta-, hexa nyl) propyl) (Mexoryl(R) XL) 40 and hepta-thionine Sulfoximine) in very small compatible 4,4'-(6-4-(1,1-dimethyl)aminocarbonyl)phenylamino dosages, also (metal) chelators (for example alpha-hydroxy 1,3,5-triazine-2,4-diyl)diimino-bis-(benzoic acid-2- fatty acids, palmitic acid, phytic acid, lactoferrine), alpha ethylhexyl ester) (Uvasorb HEB) hydroxy acids (for example citric acid, lactic acid, malic 3-(4-methylbenzylidene)-D.L-camphor (Neo Heliopan R. acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, MBC) 45 EDTA, EGTA and derivatives thereof, unsaturated fatty acids 3-benzylidene camphor and derivatives thereof (for example linoleic acid, oleic acid), salicylic acid-2-ethylhexyl ester (Neo Heliopan ROS) folic acid and derivatives thereof, ubiquinone and ubiquinol 4-dimethylaminobenzoic acid-2-ethylhexyl ester (Padi and derivatives thereof, vitamin C and derivatives thereof (for mate O) example ascorbyl palmitate, Mgascorbyl phosphate, ascor hydroxy-4-methoxybenzophenone-5-sulfonic acid and Na 50 byl acetate), tocopherols and derivatives (for example vita salt min E acetate), Vitamin A and derivatives (vitamin A palmi 2,2'-methylene bis-(6-(2H-benzotriazol-2-yl)-4-1,1,3,3- tate) and coniferyl benzoate of benzoin resin, rutinic acid and tetramethylbutyl)phenol) (Tinosorb(RM) derivatives thereof, glycosyl rutin, ferulic acid, furfurylidene phenylene bis-benzimidazyl tetrasulfonic acid disodium glucitol, carnosine, butyl hydroxytoluene, butyl hydroxyani salt (Neo Heliopan RAP) 55 sole, nordihydroguaiac resin acid, nordihydroguaiaretic acid, 2,4-bis-(4-(2-ethylhexyloxy)-2-hydroxyphenyl]-6-(4- trihydroxybutyrophenone, uric acid and derivatives thereof, methoxyphenyl)-1,3,5-triazine (Tinosorb(RS) mannose and derivatives thereof. Superoxide dismutase, tita benzylidene malonate polysiloxane (Parsol R SLX) nium dioxide (for example dispersions in ethanol), Zinc and menthyl anthranilate (Neo Heliopan R MA) derivatives thereof (for example ZnO, ZnSO), selenium and 2-(4-diethylamino-2-hydroxybenzoyl)benzoic acid hexyl 60 derivatives thereof (for example selenium methionine), stil ester (Uvinul R A Plus) benes and derivatives thereof (for example stilbene oxide, indanylidene compounds in accordance with DE 100 55 trans-stilbene oxide) and derivatives of these active sub 940 (=WO 02/38537). stances Suitable for the purposes of the invention (salts, esters, Advantageous primary and also secondary Sun protection ethers, Sugars, nucleotides, nucleosides, peptides and lipids). factors are mentioned in WO 2005 123101 A1. Advanta 65 Advantageous inorganic secondary light protection pig geously, these preparations contain at least one UVA filter ments are finely dispersed metal oxides and metal salts which and/or at least one UVB filter and/or at least one inorganic are also mentioned in WO 2005 123101 A1. The total quantity US 9,125,936 B2 15 16 of inorganic pigments, in particular hydrophobic inorganic piomelanocortin peptides such as ACTH, alpha-MSH, pep micro-pigments in the finished cosmetic preparation accord tide analogues thereof and other substances which bind to the ing to the present invention is advantageously from 0.1 to melanocortin receptor, peptides such as Val-Gly-Val-Ala 30% by weight, preferably 0.5 to 10.0% by weight, in each Pro-Gly, Lys-Ile-Gly-Arg-Lys or Leu-Ile-Gly-Lys, purines, case based on the total weight of the preparation. pyrimidines, folic acid, copper salts such as copper gluconate, Also preferred are particulate UV filters or inorganic pig chloride or pyrrolidonate, 1,3,4-oxadiazole-2-thiols such as ments, which can optionally be hydrophobed, can be used, 5-pyrazin-2-yl-1,3,4-oxadiazole-2-thiol, curcumin, Zinc dig such as the oxides of titanium (TiO), Zinc (ZnO), iron lycinate (Zn(Gly)), manganese(II) bicarbonate complexes (Fe2O), Zirconium (ZrO2), silicon (SiO2), manganese (e.g. (“pseudocat-alases') as described for example in EPO 584 MnO), aluminium (Al2O), cerium (e.g. CeO) and/or mix 10 178, tetrasubstituted cyclohexene derivatives as described for tures thereof. example in WO 2005/032501, isoprenoids as described in L. Actives Modulating Skin and/or Hair Pigmentation WO 2005/102252 and in WO 2006/010661, melanin deriva Preferred active ingredients for skin and/or hair lightening tives such as Melasyn-100 and MelanZe, diacyl glycerols, are selected from the group consisting of: aliphatic or cyclic diols, psoralens, prostaglandins and ana kojic acid (5-hydroxy-2-hydroxymethyl-4-pyranone), kojic 15 logues thereof, activators of adenylate cyclase and com acid derivatives, preferably kojic acid dipalmitate, arbutin, pounds which activate the transfer of melanosomes to kera ascorbic acid, ascorbic acid derivatives, preferably magne tinocytes such as serine proteases or agonists of the PAR-2 sium ascorbyl phosphate, hydroquinone, hydroquinone receptor, extracts of plants and plant parts of the chrysanthe derivatives, resorcinol, resorcinol derivatives, preferably mum species, san-guisorba species, walnut extracts, urucum 4-alkylresorcinols and 4-(1-phenylethyl) 1,3-dihydroxyben extracts, rhubarb extracts, microalgae extracts, in particular Zene (phenylethyl resorcinol), cyclohexylcarbamates (prefer Isochrysis galbana, trehalose, erythru-lose and dihydroxyac ably one or more cyclohexyl carbamates disclosed in WO etone. Flavonoids which bring about skin and hair tinting or 2010/122178 and WO 2010/097480), sulfur-containing mol browning (e.g. quercetin, rhamnetin, kaempferol, fisetin, ecules, preferably glutathione or cysteine, alpha-hydroxy genistein, daidzein, chrysin and api-genin, epicatechin, acids (preferably citric acid, lactic acid, malic acid), salts and 25 dioSmin and dioSmetin, morin, quercitrin, naringenin, hespe esters thereof, N-acetyl tyrosine and derivatives, undecenoyl ridin, phloridzin and phloretin) can also be used. phenylalanine, gluconic acid, chromone derivatives, prefer The amount of the aforementioned examples of additional ably aloesin, flavonoids, 1-aminoethyl phosphinic acid, thio active ingredients for the modulation of skin and hairpigmen urea derivatives, elagic acid, nicotinamide (niacinamide), tation (one or more compounds) in the products according to Zinc salts, preferably Zinc chloride or Zinc gluconate, thuja 30 the invention is then preferably 0.00001 to 30 wt.%, prefer plicin and derivatives, triterpenes, preferably maslinic acid, ably 0.0001 to 20 wt.%, particularly preferably 0.001 to 5 wt. sterols, preferably ergosterol, benzofuranones, preferably %, based on the total weight of the prepa-ration. senkyunolide, vinyl guiacol, ethyl guiacol, dionic acids, pref M. Anti-Ageing Actives erably octodecene dionic acid and/or azelaic acid, inhibitors In the context of the invention, anti-ageing or biogenic of nitrogen oxide synthesis, preferably L-nitroarginine and 35 agents are, for example antioxidants, matrix-metalloprotein derivatives thereof, 2,7-dinitroindazole or thiocitrulline, ase inhibitrors (MMPI), skin moisturizing agents, gly metal chelators (preferably alpha-hydroxy fatty acids, phytic cosaminglycan stimulkators, anti-inflammatory agents, acid, humic acid, bile acid, bile extracts, EDTA, EGTA and TRPV1 antagonists and plant extracts. derivatives thereof), retinoids, Soy milk and extract, serine (i) Antioxidants. amino acids (preferably glycine, histidine, protease inhibitors or lipoic acid or other synthetic or natural 40 tyrosine, tryptophane) and derivatives thereof, imidazoles active ingredients for skin and hair lightening, the latter pref (preferably urocanic acid) and derivatives thereof, pep erably used in the form of an extract from plants, preferably tides, preferably D.L-carnosine, D-carnosine, L-carnosine bearberry extract, rice extract, papaya extract, turmeric and derivatives thereof (preferably anserine), carnitine, extract, mulberry extract, bengkoang extract, nutgrass creatine, matrikine peptides (preferably lysyl-threonyl extract, liquorice root extract or constituents concentrated or 45 threonyl-lysyl-serine) and palmitoylated pentapeptides, isolated therefrom, preferably glabridin or licochalcone A, carotenoids, carotenes (preferably alpha-carotene, beta artocarpus extract, extract of rumex and ramulus species, carotene, lycopene) and derivatives thereof, lipoic acid and extracts of pine species (pinus), extracts of vitis species or derivatives thereof (preferably dihydrolipoic acid), stilbene derivatives isolated or concentrated therefrom, saxi aurothioglucose, propylthiouracil and other thiols (prefer frage extract, scutelleria extract, grape extract and/or 50 ably thioredoxine, glutathione, cysteine, cystine, cysta microalgae extract, in particular Tetraselmis suecica Extract. mine and glycosyl, N-acetyl, methyl, ethyl, propyl, amyl. Preferred skin lighteners as component (b) are kojic acid butyl and lauryl, palmitoyl, oleyl, gamma-linoleyl, choles and phenylethyl resorcinol as tyrosinase inhibitors, beta- and teryl, glyceryl and oligoglyceryl esters thereof) and salts alpha-arbutin, hydroquinone, nicotinamide, dioic acid, Mg thereof, dilauryl thiodipropionate, distearyl thiodipropi ascorbyl phosphate and vitamin C and its derivatives, mul 55 onate, thiodipropionic acid and derivatives thereof (prefer berry extract, Bengkoang extract, papaya extract, turmeric ably esters, ethers, peptides, lipids, nucleotides, nucleo extract, nutgrass extract, licorice extract (containing glycyr sides and salts) and Sulfoximine compounds (preferably rhizin), alpha-hydroxy-acids, 4-alkylresorcinols, 4-hy buthionine Sulfoximines, homocysteine Sulfoximine, droxyanisole. These skin lighteners are preferred due to their buthionine Sulfones, penta-, hexa-, heptathionine Sulfox very good activity, in particular in combination with Sclar 60 imine) in very small tolerated doses (e.g. pmol to Lmol/kg), eolide according to the present invention. In addition, said also (metal) chelators (preferably alpha-hydroxy fatty preferred skin lighteners are readily available. acids, palmitic acid, phytic acid, lactoferrin, alpha-hy Advantageous skin and hair tanning active ingredients in droxy acids (preferably citric acid, lactic acid, malic acid), this respectare Substrates or Substrate analogues of tyrosinase humic acid, bile acid, bile extracts, tannins, bilirubin, such as L-tyrosine, N-acetyl tyrosine, L-DOPA or L-dihy 65 biliverdin, EDTA, EGTA and derivatives thereof), unsatur droxyphenylalanine, Xanthine alkaloids such as caffeine, ated fatty acids and derivatives thereof (preferably gamma theobromine and theophyl-line and derivatives thereof, proo linolenic acid, linoleic acid, oleic acid), folic acid and US 9,125,936 B2 17 18 derivatives thereof, ubiquinone and derivatives thereof, (preferably as described in WO 2005 123101 A1, incorpo ubiquinol and derivatives thereof, vitamin C and deriva rated herein by reference) as e.g. SymMatrix (company tives (preferably ascorbyl palmitate, Mg ascorbyl phos Symrise, INCI: Maltodextrin, Rubus Fruticosus (Black phate, ascorbyl acetate, ascorbyl glucoside), tocopherols berry) Leaf Extract). Preferred actives of are selected from and derivatives (preferably vitamin E acetate), vitamin A the group consisting of retinyl palmitate, ursolic acid, and derivatives (vitamin A palmitate) and coniferyl ben extracts from the leaves of the Rosaceae family, sub-family Zoate of benzoic resin, rutinic acid and derivatives thereof, Rosoideae, genistein and daidzein. flavonoids and glycosylated precursors thereof, in particu (III) Skin-moisturizing agents. Preferred skin moisturizing lar quercetin and derivatives thereof, preferably alpha-glu agents are selected from the group consisting of alkane cosyl rutin, roSmarinic acid, carnosol, carnosolic acid, res 10 Veratrol, caffeic acid and derivatives thereof, sinapic acid diols or alkane triols comprising 3 to 12 carbon atoms, and derivatives thereof, ferulic acid and derivatives thereof, preferably C-Co-alkane diols and C-Co-alkane triols. curcuminoids, chlorogenic acid and derivatives thereof, More preferably the skin moisturizing agents are selected retinoids, preferably retinyl palmitate, retinol or tretinoin, from the group consisting of glycerol. 1,2-propylene gly ursolic acid, levulinic acid, butyl hydroxytoluene, butyl 15 col, 1.2-butylene glycol. 1,3-butylene glycol, 1.2-pen hydroxyanisole, nordihydroguaiac acid, nordihydroguai tanediol. 1.2-hexanediol, 1.2-octanediol and 1.2-de aretic acid, trihydroxybutyrophenone, uric acid and deriva canediol. tives thereof, mannose and derivatives thereof, Zinc and (iv) Glycosaminoglycan stimulators. Preferred compositions derivatives thereof (preferably ZnO, ZnSO), selenium and comprise Substances stimulating the synthesis of gly derivatives thereof (preferably selenium methionine), cosaminoglycans selected from the group consisting of superoxide dismutase, stilbenes and derivatives thereof hyaluronic acid and derivatives or salts, Subliskin (Sed (preferably stilbene oxide, trans-stilbene oxide) and the erma, INCI: Sinorhizobium Meliloti Ferment Filtrate, derivatives (salts, esters, ethers, Sugars, nucleotides, Cetyl Hydroxyethylcellulose, Lecithin), Hyalufix (BASF, nucleosides, peptides and lipids) of these cited active INCI: Water, Butylene Glycol, Alpinia galanga leaf ingredients which are suitable according to the invention or 25 extract, Xanthan Gum, Caprylic/Capric Triglyceride), extracts or fractions of plants having an antioxidant effect, Stimulhyal (Soliance, INCI: Calcium ketogluconate), Syn preferably green tea, rooibos, honeybush, grape, rosemary, Glycan (DSM, INCI: Tetradecyl Aminobutyroylvalylami Sage, melissa, thyme, lavender, olive, oats, cocoa, ginkgo, nobutyric Urea Trifluoroacetate, Glycerin, Magnesium ginseng, liquorice, honeysuckle, Sophora, pueraria, pinus, chloride), Kalpariane (Biotech Marine), DC Upregulex citrus, Phyllanthus emblica or St. John’s wort, grape seeds, 30 (Distinctive Cosmetic Ingredients, INCI: Water. Butylene wheat germ, Phyllanthus emblica, coenzymes, preferably Glycol, Phospholipids, Hydrolyzed Sericin), glucosamine, coenzyme Q10, plastoquinone and menaquinone. Pre N-acetyl glucosamine, retinoids, preferably retinol and ferred antioxidants are selected from the group consisting Vitamin A, Arctium lappa fruit extract, Eriobotrya of vitamin A and derivatives, vitamin C and derivatives, japonica extract, Genkwanin, N-Methyl-L-serine, (-)-al tocopherol and derivatives, preferably tocopheryl acetate, 35 pha-bisabolol or synthetic alpha-bisabolol Such as e.g. and ubiquinone. Dragosantol and Dragosantol 100 from Symrise, oat glu (ii) Matrix-Metalloproteinase inhibitors (MMPI). Preferred can, Echinacea purpurea extract and soy protein hydroly compositions comprise matrix-metalloproteinase inhibi sate. Preferred actives are selected from the group consist tors, especially those inhibiting matrix-metalloproteinases ing of hyaluronic acid and derivatives or salts, retinol and enzymatically cleaving collagen, selected from the group 40 derivatives, (-)-alpha-bisabolol or synthetic alpha-bisab consisting of: ursolic acid, retinyl palmitate, propyl gallate, olol such as e.g. Dragosantol and Dragosantol 100 from precocenes, 6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)- Symrise, oat glucan, Echinacea purpurea extract, benzopyran, 3,4-dihydro-6-hydroxy-7-methoxy-2,2-dim Sinorhizobium Meliloti Ferment Filtrate, Calcium ketoglu ethyl-1(2H)-benzopyran, benzamidine hydrochloride, the conate, Alpinia galanga leaf extract and tetradecyl ami cysteine proteinase inhibitors N-ethylmalemide and epsi 45 nobutyroylvalylaminobutyric urea trifluoroacetate. lon-amino-n-caproic acid of the serinprotease inhibitors: (v) Anti-inflammatory agents. The compositions may also phenylmethylsulfonylfluoride, collhibin (company Pen contain anti-inflammatory and/or redness and/or itch ame tapharm; INCI: hydrolysed rice protein), oenotherol (com liorating ingredients, in particular steroidal Substances of pany Soliance, INCI: propylene glycol, aqua, Oenothera the corticosteroid type selected from the group consisting biennis root extract, ellagic acid and ellagitannins, for 50 of hydrocortisone, dexamethasone, dexamethasone phos example from pomegranate), phosphoramidone hinokitiol, phate, methyl prednisolone or cortisone, are advanta EDTA, galardin, EquiStat (company Collaborative Group; geously used as anti-inflammatory active ingredients or apple fruit extract, Soya seed extract, ursolic acid, Soya active ingredients to relieve reddening and itching, the list isoflavones and soya proteins), sage extracts, MDI (com of which can be extended by the addition of other steroidal pany Atrium; INCI: glycosaminoglycans), fermiskin 55 anti-inflammatories. Non-steroidal anti-inflammatories (company Silab/Mawi; INCI: water and lentinus edodes can also be used. Examples which can be cited here are extract), actimp 1.9.3 (company Expanscience/Rahn: oxicams such as piroxicam or tenoxicam, Salicylates Such INCI: hydrolysed lupine protein), lipobelle soyaglycone as aspirin, disalcid, Solprin or fendosal; acetic acid deriva (company Mibelle; INCI: alcohol, polysorbate 80, lecithin tives such as diclofenac, fenclofenac, indomethacin, Sulin and Soy isoflavones), extracts from green and black tea and 60 dac, tolmetin or clindanac; fenamates Such as mefenamic, further plant extracts, which are listed in WO02069992 A1 meclofenamic, flufenamic or niflumic; propionic acid (see tables 1-12 there, incorporated herein by reference), derivatives such as ibuprofen, naproxen, benoxaprofen or proteins or glycoproteins from soya, hydrolysed proteins pyrazoles such as phenylbutaZone, oxyphenylbutaZone, from rice, pea or lupine, plant extracts which inhibit febraZone oraZapropaZone. Anthranilic acid derivatives, in MMPs, preferably extracts from shitake mushrooms, 65 particular avenanthramides described in WO 2004 047833 extracts from the leaves of the Rosaceae family, sub-family A1, are preferred anti-itch ingredients in a composition Rosoideae, quite particularly extracts of blackberry leaf according to the present invention. US 9,125,936 B2 19 20 Also useful are natural or naturally occurring anti-inflam menthanecarboxylic acid amides (in this case preferably matory mixtures of substances or mixtures of substances menthanecarboxylic acid-N-ethylamide WS3 or N'-(men that alleviate reddening and/or itching, in particular thanecarbonyl)glycmethylester WS5, as described in U.S. extracts or fractions from camomile, Aloe vera, Commi Pat. No. 4,150,052, menthanecarboxylic acid-N-(4-cy phora species, Rubia species, willow, willow-herb, oats, anophenyl)amide or menthanecarboxylic acid-N-(4-cya calendula, arnica, St John's wort, honeysuckle, rose nomethylphenyl)amideas described in WO 2005049553 A1, mary, Passiflora incarnata, witch hazel, ginger or methanecarboxylic acid-N-(alkoxyalkyl)amides), menthone Echinacea; preferably selected from the group consist and menthone derivatives (for example L-menthone glycerol ing of extracts or fractions from camomile, Aloe vera, ketal), 2,3-dimethyl-2-(2-propyl)-butyric acid derivatives oats, calendula, arnica, honeysuckle, rosemary, witch 10 (for example 2,3-dimethyl-2-(2-propyl)-butyric acid-N-me hazel, ginger or Echinacea, and/or pure Substances, thylamide IWS23), isopulegol or its esters (I-(-)-isopulegol, preferably alpha-bisabolol, apigenin, apigenin-7-gluco I-(-)-isopulegolacetate), menthane derivatives (for example side, gingerols, shogaols, gingerdiols, dehydrogingerdi p-menthane-3,8-diol), cubebol or synthetic or natural mix ones, paradols, natural or naturally occurring avenan tures, containing cubebol, pyrrolidone derivatives of thramides, preferably tranilast, avenanthramide A, 15 cycloalkyldione derivatives (for example 3-methyl-2(1-pyr avenanthramide B, avenanthramide C, non-natural or rolidinyl)-2-cyclopentene-1-one) or tetrahydropyrimidine-2- non-naturally occurring avenanthramides, preferably one (for example iciline or related compounds, as described dihydroavenanthramide D, dihydroavenanthramide E. in WO 2004/026840), further carboxamides (for example avenanthramide D, avenanthramide E. avenanthramide N-(2-(pyridin-2-yl)ethyl)-3-p-menthanecarboxamide O F. boswellic acid, phytosterols, glycyrrhizin, glabridin related compounds), (1R,2S.5R)-N-(4-Methoxyphenyl)-5- and licochalcone A; preferably selected from the group methyl-2-(1-isopropyl)cyclohexane-carboxamide IWS12, consisting of alpha-bisabolol, natural avenanthramides, oxamates (preferably those described in EP 2033688A2). non-natural avenanthramides, preferably dihydroav O. Anti-Microbial Agents enanthramide D (as described in WO 2004 047833A1), Suitable anti-microbial agents are, in principle, all Sub boswellic acid, phytosterols, glycyrrhizin, and licochal 25 stances effective against Gram-positive bacteria, such as, for cone A, and/or allantoin, panthenol, lanolin, (pseudo-) example, 4-hydroxybenzoic acid and its salts and esters, ceramides preferably Ceramide 2, hydroxypropyl bis N-(4-chlorophenyl)-N'-(3,4-dichlorophenyl)urea, 2,4,4'- palmitamide MEA, cetyloxypropyl glyceryl trichloro-2'-hydroxy-diphenyl ether (triclosan), 4-chloro-3, methoxypropyl myristamide, N-(1-hexadecanoyl)-4- 5-dimethyl-phenol, 2,2'-methylenebis(6-bromo-4-chlo hydroxy-L-proline (1-hexadecyl) ester, hydroxyethyl 30 rophenol), 3-methyl-4-(1-methylethyl)phenol, 2-benzyl-4- palmityl oxyhydroxypropyl palmitamide, glycosphin chloro-phenol, 3-(4-chlorophenoxy)-1,2-propanediol. golipids, phytosterols, chitosan, mannose, lactose and 3-iodo-2-propynyl butylcarbamate, chlorhexidine, 3,4,4'- B-glucans, in particular 1,3-1,4-B-glucan from oats. trichlorocarbanilide (TTC), antibacterial fragrances, thymol, (vi) TRPV1 antagonists. Suitable compounds which reduce thyme oil, eugenol, oil of cloves, menthol, mint oil, farnesol, the hypersensitivity of skin nerves based on their action as 35 phenoxyethanol, glycerol monocaprate, glycerol monoca TRPV1 antagonists, encompass e.g. trans-4-tert-butyl prylate, glycerol monolaurate (GML), diglycerol monoca cyclohexanol as described in WO 2009 087242 A1, or prate (DMC), salicylic acid N-alkylamides, such as, for indirect modulators of TRPV1 by an activation of the L-re example, n-octylsalicylamide or n-decylsalicylamide. ceptor, e.g. acetyl tetrapeptide-15, are preferred. P. Enzyme Inhibitors (vii) Botanical extracts. The compositions may also contain 40 Suitable enzyme inhibitors are, for example, esterase various extracts of plants, such as for example extracts of inhibitors. These are preferably trialkyl citrates, such as tri Ginkgo biloba, Oleacea europensis, Glyzyrrhiza glabra, methyl citrate, tripropyl citrate, triisopropyl citrate, tributyl Vaccinium myrtillus, Trifolium pratense, Litchi Sinensis, citrate and, in particular, triethylcitrate (Hydagen CAT). The Vitis, vinifera, Brassica oleracea, Punica granatum, substances inhibit enzyme activity, thereby reducing the for Petroselinium crispum, Centella asiatica, Passiflora incar 45 mation of odour. Other substances which are suitable esterase nata, Medicago sativa, Melissa officinalis, Valeriana offi inhibitors are sterol Sulfates or phosphates, such as, for cinalis, Castanea sativa, Salix alba and Hapagophytum example, lanosterol, cholesterol, campesterol, Stigmasterol procumbens. and sitosterol Sulfate or phosphate, dicarboxylic acids and N. Cooling Agents esters thereof. Such as, for example, glutaric acid, monoethyl The compositions may also contain one or more Substances 50 glutarate, diethyl glutarate, adipic acid, monoethyl adipate, with a physiological cooling effect (cooling agents), which diethyl adipate, malonic acid and diethyl malonate, hydroxy are preferably selected here from the following list: menthol carboxylic acids and esters thereof. Such as, for example, and mentholderivatives (for example L-menthol, D-menthol, citric acid, malic acid, tartaric acid or diethyl tartrate, and Zinc racemic menthol, isomenthol, neoisomenthol, neomenthol) glycinate. menthylethers (for example (I-menthoxy)-1,2-propandiol. 55 Q. Odour Absorbers and Antiperspirant Active Agents (I-menthoxy)-2-methyl-1,2-propandiol. I-menthyl-methyl Suitable odour absorbers are substances which are able to ether), menthylesters (for examplementhylformiate, menthy absorb and largely retain odour-forming compounds. They lacetate, menthylisobutyrate, menthylactates, L-menthyl-L- lower the partial pressure of the individual components, thus lactate, L-menthyl-D-lactate, menthyl-(2-methoxy)acetate, also reducing their rate of diffusion. It is important that per menthyl-(2-methoxyethoxy-)acetate, menthylpyro 60 fumes must remain unimpaired in this process. Odour absorb glutamate), menthylcarbonates (for example menthylpropy ers are not effective against bacteria. They comprise, for leneglycolcarbonate, menthylethyleneglycolcarbonate, men example, as main constituent, a complex Zinc salt of ricinoleic thylglycerolcarbonate or mixtures thereof), the semi-esters of acid or specific, largely odour-neutral fragrances which are menthols with a dicarboxylic acid or derivatives thereof (for known to the person skilled in the art as “fixatives, such as, example mono-menthylsuccinate, mono-menthylglutarate, 65 for example, extracts of labdanum or styrax or certainabietic mono-menthylmalonate, O-menthyl Succinic acid ester-N,N- acid derivatives. The odour masking agents are fragrances or (dimethyl)amide, O-menthyl Succinic acid ester amide), perfume oils, which, in addition to their function as odour US 9,125,936 B2 21 22 masking agents, give the deodorants their respective fra LameponRUD (protein/undecylenic acid condensate), Zinc grance note. Perfume oils which may be mentioned are, for pyrithione, aluminium pyrithione and magnesium pyrithione/ example, mixtures of natural and synthetic fragrances. Natu dipyrithione magnesium Sulfate. ral fragrances are extracts from flowers, stems and leaves, S. Carriers and Hydrotropes fruits, fruit peels, roots, woods, herbs and grasses, needles Preferred cosmetics carrier materials are solid or liquid at and branches, and resins and balsams. Also Suitable are ani 25° C. and 1013 mbar (including highly viscous substances) mal products, such as, for example, civet and castoreum. as for example glycerol, 1.2-propylene glycol, 1.2-butylene Typical synthetic fragrance compounds are products of the glycol. 1,3-propylene glycol. 1,3-butylene glycol, ethanol, ester, ether, aldehyde, ketone, alcohol, and hydrocarbon type. water and mixtures of two or more of said liquid carrier Fragrance compounds of the ester type are, for example, 10 materials with water. Optionally, these preparations accord benzyl acetate, p-tert-butylcyclohexyl acetate, linallyl acetate, ing to the invention may be produced using preservatives or phenylethyl acetate, linallyl benzoate, benzyl formate, allyl solubilizers. Other preferred liquid carrier substances, which cyclohexylpropionate, Styrallyl propionate and benzyl sali may be a component of a preparation according to the inven cylate. The ethers include, for example, benzyl ethyl ether, tion are selected from the group consisting of oils such as and the aldehydes include, for example, the linear alkanals 15 Vegetable oil, neutral oil and mineral oil. having 8 to 18 carbon atoms, citral, citronellal, citronelly Preferred solid carrier materials, which may be a compo loxyacetaldehyde, cyclamen aldehyde, hydroxycitronellal, nent of a preparation according to the invention are hydrocol lilial and bourgeonal, the ketones include, for example, the loids, Such as starches, degraded starches, chemically or ionones and methyl cedryl ketone, the alcohols include anet physically modified Starches, dextrins, (powdery) maltodex hole, citronellol, eugenol, isoeugenol, geraniol, linaool, phe trins (preferably with a dextrose equivalent value of 5 to 25, nylethyl alcohol and terpineol, and the hydrocarbons include preferably of 10-20), lactose, silicon dioxide, glucose, modi mainly the terpenes and balsams. Preference is, however, fied celluloses, gum arabic, ghatti gum, traganth, karaya, given to using mixtures of different fragrances which together carrageenan, pullulan, curdlan, Xanthan gum, gellan gum, produce a pleasing fragrance note. Essential oils of relatively guar flour, carobbean flour, alginates, agar, pectin and inulin low volatility, which are mostly used as aroma components, 25 and mixtures of two or more of these solids, in particular are also suitable as perfume oils, e.g. sage oil, camomile oil, maltodextrins (preferably with a dextrose equivalent value of oil of cloves, melissa oil, mint oil, cinnamon leaf oil, linden 15-20), lactose, silicon dioxide and/or glucose. flower oil, juniperberry oil, Vetiver oil, olibanum oil, gal In addition, hydrotropes, for example ethanol, isopropyl banum oil, labdanum oil and lavandin oil. Preference is given alcohol or polyols, may be used to improve flow behaviour. to using bergamot oil, dihydromyrcenol, lilial, lyral, cit 30 Suitable polyols preferably contain 2 to 15 carbonatoms and ronellol, phenylethyl alcohol, C-hexylcinnamaldehyde, at least two hydroxyl groups. The polyols may contain other geraniol, benzylacetone, cyclamen aldehyde, linalool, bois functional groups, more especially amino groups, or may be ambrene forte, ambroxan, indole, hedione, Sandelice, lemon modified with nitrogen. Typical examples are oil, mandarin oil, orange oil, allyl amylglycolate, cyclovertal, glycerol; lavandin oil, clary sage oil, 3-damascone, geranium oil bour 35 alkylene glycols such as, for example, ethylene glycol, bon, cyclohexyl salicylate, Vertofix coeur, iso-E-super, Fix diethylene glycol, propylene glycol, butylene glycol, olide NP, evernyl, iraldeingamma, phenylacetic acid, geranyl hexylene glycol and polyethylene glycols with an aver acetate, benzyl acetate, rose oxide, romilat, irotyl and age molecular weight of 100 to 1000 Dalton; floramat alone or in mixtures. technical oligoglycerol mixtures with a degree of self Suitable astringent antiperspirant active ingredients are 40 condensation of 1.5 to 10, such as for example technical primarily salts of aluminium, Zirconium or of zinc. Such diglycerol mixtures with a diglycerol content of 40 to Suitable antihydrotic active ingredients are, for example, alu 50% by weight; minium chloride, aluminium chlorohydrate, aluminium methylol compounds such as, in particular, trimethylol dichlorohydrate, aluminium sesquichlorohydrate and com ethane, trimethylol propane, trimethylol butane, pen plex compounds thereof, e.g. with 1,2-propylene glycol, alu 45 taerythritol and dipentaerythritol; minium hydroxyallantoinate, aluminium chloride tartrate, lower alkyl glucosides, particularly those containing 1 to 8 aluminium Zirconium trichlorohydrate, aluminium Zirco carbonatoms in the alkyl group, for example methyl and nium tetrachlorohydrate, aluminium zirconium pentachloro butyl glucoside; hydrate and complex compounds thereof, e.g. with amino Sugar alcohols containing 5 to 12 carbon atoms, for acids, Such as glycine. 50 example sorbitol or mannitol, R. Film Formers and Anti-Dandruff Agents Sugars containing 5 to 12 carbon atoms, for example glu Standard film formers are, for example, chitosan, microc cose or Sucrose; rystalline chitosan, quaternized chitosan, polyvinyl pyrroli amino Sugars, for example glucamine; done, vinyl pyrrolidone/vinyl acetate copolymers, polymers dialcoholamines, such as diethanolamine or 2-aminopro of the acrylic acid series, quaternary cellulose derivatives, 55 pane-1,3-diol. collagen, hyaluronic acid and salts thereof and similar com T. Preservatives pounds. Suitable preservatives are, for example, phenoxyethanol, Suitable antidandruff agents are Pirocton Olamin (1-hy formaldehyde solution, parabens, pentanediol or Sorbic acid droxy-4-methyl-6-(2,4,4-trimethylpentyl)-2-(1H)-pyridi and the other classes of compounds listed in AppendiX 6. none monoethanolamine salt), Baypival(R) (Climbazole), 60 Parts A and B of the Kosmetikverordnung (“Cosmetics Direc Ketoconazol(R) (4-acetyl-1-4-2-(2,4-dichlorophenyl) r-2- tive”). (1H-imidazol-1-ylmethyl)-1,3-dioxylan-c-4-ylmethoxy U. Perfume Oils and Fragrances phenyl-piperazine, ketoconazole, elubiol, selenium disul Suitable perfume oils are mixtures of natural and synthetic fide, colloidal sulfur, sulfur polyethylene glycol sorbitan perfumes. Natural perfumes include the extracts of blossoms monooleate, sulfur ricinol polyethoxylate, sulfur tar distil 65 (lily, lavender, rose, jasmine, neroli, ylang-ylang), stems and late, Salicylic acid (or in combination with hexachlorophene), leaves (geranium, patchouli, petitgrain), fruits (anise, corian undecylenic acid, monoethanolamide SulfoSuccinate Nasalt, der, caraway, juniper), fruit peel (bergamot, lemon, orange), US 9,125,936 B2 23 24 roots (nutmeg, angelica, celery, cardamom, Costus, iris, cal The formulations according to the invention are preferably mus), woods (pinewood, sandalwood, guaiac wood, cedar in the form of an emulsion, e.g. W/O (water-in-oil), O/W wood, rosewood), herbs and grasses (tarragon, lemon grass, (oil-in-water), W/O/W (water-in-oil-in-water), O/W/O (oil sage, thyme), needles and branches (spruce, fir, pine, dwarf in-water-in-oil) emulsion, PIT emulsion, Pickering emulsion, pine), resins and balsams (galbanum, elemi, benzoin, myrrh, 5 emulsion with a low oil content, micro- or nanoemulsion, a olibanum, opoponax). Animal raw materials, for example Solution, e.g. in oil (fatty oils or fatty acid esters, in particular civet and beaver, may also be used. Typical synthetic perfume C-C fatty acid C-Co esters) or silicone oil, dispersion, compounds are products of the ester, ether, aldehyde, ketone, Suspension, creme, lotion or milk, depending on the produc alcohol and hydrocarbon type. Examples of perfume com tion method and ingredients, a gel (including hydrogel, pounds of the ester type are benzyl acetate, phenoxyethyl 10 hydrodispersion gel, oleogel), spray (e.g. pump spray or isobutyrate, p-tert.butyl cyclohexylacetate, linallyl acetate, spray with propellant) or a foam or an impregnating Solution dimethylbenzyl carbinyl acetate, phenyl ethyl acetate, linallyl for cosmetic wipes, a detergent, e.g. Soap, synthetic detergent, benzoate, benzyl formate, ethylmethyl phenylglycinate, allyl liquid washing, shower and bath preparation, bath product cyclohexyl propionate, Styrallyl propionate and benzyl sali 15 (capsule, oil, tablet, salt, bath salt, Soap, etc.), effervescent cylate. Ethers include, for example, benzyl ethyl ether while preparation, a skin care product such as e.g. an emulsion (as aldehydes include, for example, the linear alkanals contain described above), ointment, paste, gel (as described above), ing 8 to 18 carbon atoms, citral, citronellal, citronellyloxyac oil, balsam, serum, powder (e.g. face powder, body powder), etaldehyde, cyclamen aldehyde, hydroxycitronellal, lilial and a mask, a pencil, Stick, roll-on, pump, aerosol (foaming, non bourgeonal. Examples of Suitable ketones are the ionones, foaming or post-foaming), a deodorant and/or antiperspirant, -isomethylionone and methylcedryl ketone. Suitable alco mouthwash and mouth rinse, a foot care product (including hols are anethol, citronellol, eugenol, isoeugenol, geraniol, keratolytic, deodorant), an insect repellent, a Sunscreen, after linalool, phenylethyl alcohol and terpineol. The hydrocar Sun preparation, a shaving product, aftershave balm, pre- and bons mainly include the terpenes and balsams. However, it is aftershave lotion, a depilatory agent, a hair care product Such preferred to use mixtures of different perfume compounds 25 as e.g. shampoo (including 2-in-1 shampoo, anti-dandruff which, together, produce an agreeable perfume. Other Suit shampoo, baby shampoo, shampoo for dry scalps, concen able perfume oils are essential oils of relatively low volatility trated shampoo), conditioner, hair tonic, hair water, hair rinse, which are mostly used as aroma components. Examples are styling creme, pomade, perm and setting lotion, hair spray, sage oil, camomile oil, clove oil, melissa oil, mint oil, cinna Styling aid (e.g. gel or wax), hair Smoothing agent (detangling mon leaf oil, lime-blossom oil, juniper berry oil, Vetiver oil, 30 agent, relaxer), hair dye such as e.g. temporary direct-dyeing olibanum oil, galbanum oil, ladanum oil and lavendin oil. The hair dye, semi-permanent hair dye, permanent hair dye, hair following are preferably used either individually or in the conditioner, hair mousse, eye care product, make-up, make form of mixtures: bergamotoil, dihydromyrcenol, lilial, lyral, up remover or baby product. citronellol, phenylethyl alcohol, hexylcinnamaldehyde, The formulations according to the invention are particu geraniol, benzyl acetone, cyclamen aldehyde, linalool, Bois 35 larly preferably in the form of an emulsion, in particular in the ambrene Forte, Ambroxan, indole, hedione, Sandelice, citrus form of a W/O, O/W, W/O/W, O/W/O emulsion, PIT emul oil, mandarin oil, orange oil, allylamylglycolate, cyclovertal, Sion, Pickering emulsion, emulsion with a low oil content, lavendin oil, clary oil, damascone, geranium oil bourbon, micro- or nanoemulsion, a gel (including hydrogel, hydrodis cyclohexyl salicylate, Vertofix Coeur, Iso-E-Super, Fixolide persion gel, oleogel), a solution e.g. in oil (fatty oils or fatty NP, evernyl, iraldein gamma, phenylacetic acid, geranyl 40 acid esters, in particular C-C fatty acid C-C esters)) or acetate, benzyl acetate, rose oxide, romillat, irotyl and silicone oil, or a spray (e.g. pump spray or spray with propel floramat. lant). V. Dyes Auxiliary Substances and additives can be included in Suitable dyes are any of the substances suitable and quantities of 5 to 99%b.w.. preferably 10 to 80% b.w..., based approved for cosmetic purposes as listed, for example, in the 45 on the total weight of the formulation. The amounts of cos publication “Kosmetische Färbemittel of the Farbstoff-ko metic or dermatological auxiliary agents and additives and mmission der Deutschen Forschungsgemeinschaft, Verlag perfume to be used in each case can easily be determined by Chemie, Weinheim, 1984, pages 81 to 106. Examples include the person skilled in the art by simple trial and error, depend cochineal red A (C.I. 16255), patent blue V (C.I. 42051), ing on the nature of the particular product. indigotin (C.I. 73015), chlorophyllin (C.I. 75810), quinoline 50 The preparations can also contain water in a quantity of up yellow (C.I. 47005), titanium dioxide (C.I. 77891), indan to 99% b.w.. preferably 5 to 80% b.w..., based on the total threne blue RS (C.I. 69800) and madder lake (C.I. 58000). weight of the preparation. Luminol may also be present as a luminescent dye. Advanta Pharmaceutical Compositions geous coloured pigments are for example titanium dioxide, Another embodiment of the present invention refers to a mica, iron oxides (e.g. FeO FeO. FeC(OH)) and/or tin 55 pharmaceutical composition comprising the new ginger oxide. Advantageous dyes are for example carmine, Berlin extract, containing the extract in an amount of from about blue, chromium oxide green, ultramarine blue and/or manga 0.01 to about 1, preferably from about 0.1 to about 0.5% nese violet. b.w.—calculated on the total composition. Preferred compositions according to the present inventions Pharmaceutical compositions according to the present are selected from the group of products for treatment, pro 60 invention may include similar additives as already explained tecting, care and cleansing of the skin and/or hair or as a for the cosmetic application, Such as for example oil bodies or make-up product, preferably as a leave-on product (meaning emulsifiers and in particular co-actives Supporting the ben that the one or more compounds of formula (I) stay on the skin eficial properties of the new ginger extracts. It should also be and/or hair for a longer period of time, compared to rinse-off mentioned that several actives cited in the following can also products, so that the moisturizing and/or anti-ageing and/or 65 be incorporated in cosmetic formulations, so-called "cosme wound healing promoting action thereof is more pro ceuticals’. Therefore, the border between cosmetic and phar nounced). maceutical compositions is in flow and it should be under US 9,125,936 B2 25 26 stood that components cited for one application are Recent studies have also shown that it can be used as a mild recommended for the other mutatis-mutandis without literal anti-depressant. For respiratory tract infections, it has repetition. better coverage of atypical organisms, including Myco A. Anti-Irritation Agents plasma and legionellosis. It was first marketed by Eli An important group of co-actives encompass anti-irritant Lilly and Company, and it is today commonly known as agents such as for example steroidal anti-inflammatory Sub EES (erythromycin ethylsuccinate, an esterprodrug that stances of the corticosteroid type, Such as e.g. hydrocortisone, is commonly administered). In structure, this macrocy hydrocortisone derivatives, such as hydrocortisone 17-bu clic compound contains a 14-membered lactone ring tyrate, dexamethasone, dexamethasone phosphate, methyl with ten asymmetric centres and two Sugars (L-cladi prednisolone or cortisone; non-steroidal anti-inflammatories 10 nose and D-desosamine), making it a compound very like oxicams, such as piroXicam or tenoxicam, Salicylates, difficult to produce via synthetic methods. Erythromy Such as aspirin, Disalcid, Solprin or fendosal; acetic acid cin is produced from a strain of the actinomycete Sac derivatives, such as diclofenac, fenclofenac, indomethacin, charopolyspora erythraea (see U.S. Pat. No. Sulindac, tolmetin or clindanac; fenamates, such as mefe 2,653,899 Eli Lily). namic, meclofenamic, flufenamic or niflumic; propionic acid 15 derivatives, such as ibuprofen, naproxen or benoxaprofen, or (II) Dimetindene, also known as Fenistill (RS-dimethyl(2-(3- pyrazoles, such as phenylbutaZone, oxyphenylbutaZone, pyridin-2-yl)ethyl)-1H-inden-2-yl)ethyl)amine) is an febraZone or azapropaZone. Alternatively, natural anti-in antihistaminefanticholinergic used orally and locally as an flammatory Substances or reddening- and/or itching-alleviat antipruritic. ing Substances can be employed. Plant extracts, specific highly active plant extract fractions and highly pure active Substances isolated from plant extracts, can be employed like extracts, fractions and active substances from aloe vera, Commiphora species, Rubia species, Rubus species, willow, rose-bay, willowherb, oats, calendula, arnica, St. John's 25 wort, honeysuckle, ginger, chamomile, rosemary, sage, mel issa, Passiflora incarnata, Sophora japonica, witch hazel, Pueraria, Dianthus or Echinacea, as well as pure Substances, Such as, interalia, bisabolol, apigenin, apigenin-7-glucoside, roSmarinic acid, boswellic acid, phytosterols, glycyrrhizic 30 acid, glabridin, licochalcone A, 6-paradol, and anthranilic acid amides, such as, in particular, avenanthramides or dian thramides, are particularly preferred. The total amount of (III) Betamethasone (8S,9R,10S,11S,13S, 14S,16S,17R)-9- anti-irritants in a formulation or product according to the 35 fluoro-1 1,17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8, invention is preferably in the range of from 0.0001 to 20 wt. 9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta %, preferably from 0.0001 to 10 wt.%, in particular from (alpha)-phenanthren-3-one) is a potent glucocorticoid 0.001 to 5 wt.%, based on the total weight of the formulation steroid with anti-inflammatory and immunosuppressive or product, respectively. properties. Particular useful co-actives are selected from the group consisting of anti-mycotica and pain relief agents, and more 40 particularly the group consisting of erythromycin, dimetin dene, betamethasone, ibuprofen, ketoprofene, diclofenac, metronidazole, acyclovir, imiquimod, terbinafine, docosanol, cyclopyroxolamine, and their mixtures: (I) Erythromycin is a macrollide antibiotic that has an antimi 45 crobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillin. 50

Unlike other drugs with these effects, betamethasone does 55 not cause water retention. It is applied as a topical cream, ointment, foam, lotion or gel to treatitching. Betametha Sone sodium phosphate is sometimes prescribed as an intramuscular injection (I.M) for itching from various ailments, including allergic reactions to poison ivy and 60 similar plants (see U.S. Pat. No. 3,053,865 Merck). (IV) Ibuprofen (RS)-2-(4-(2-methylpropyl)phenyl)pro panoic acid) from the nomenclature isobutyl-propanoic phenolic acid) is a non-steroidal anti-inflammatory drug 65 (NSAID) used for relief of symptoms of arthritis, fever, as an analgesic (pain reliever), especially where there is an inflammatory component, and dysmenorrhea. US 9,125,936 B2 27 28

CH Ry O CH OH 5 - +/\

HC O tou O Metronidazole is an antibiotic, amebicide, and antiproto Ibuprofen is known to have an antiplatelet effect, though it 10 Zoal. It is the drug of choice for first episodes of mild 1S ity mild and that E.lived G R to-moderate Clostridium difficile infection. It is mar E.s Sanofiunderthe the US trade nameby Persibly Flagyl, in Pakistan andby tor, having been shown to constrict coronary arteries and Bangladesh also as Nidagyl by Star Laboratories, and in some other blood vessels mainly because it inhibits the 1s Thailand, as Mepagyl by That Nakhorn Patana. It is also vasodilating prostacyclin produced by cyclooxygenase marketed in UK by Milpharm Limited and Almus Phar 2 enzymes. Ibuprofen was derived from propanoic acid maceuticals. Metronidazole was developed in 1960. by the research arm of Boots Group during the 1960s and Metronidazole is used also as a gel preparation in the was patented in 1961. Originally marketed as Brufen, treatment of the dermatological conditions such as ibuprofen is available under a variety of popular trade- 20 rosaceae and fungating tumours (see U.S. Pat. No. marks, including Motrin, Nurofen, Advil, and Nuprin 2.944,061—Rhone Poulenc). (see U.S. Pat. No. 3,385,886 Boots). (VIII) Acyclovir or acyclovir (USAN, former BAN), chemi (V) Ketoprofen (RS)2-(3-benzoylphenyl)-propionic acid is cal name acycloguanosine (2-Amino-1,9-dihydro-9-((2- another one of the propionic acid class of non-steroidal hydroxyethoxy)methyl)-6H-Purin-6-one), abbreviated as anti-inflammatory drug (NSAID) with analgesic and anti- 25 ACV is a guanosine analogue antiviral drug, marketed pyretic effects. under trade names Such as Cyclovir, Herpex. Acivir, Acivi rax, Zovirax, and Xovir. The Solid active agent has a solu bility in water (20°dH) at 20° C. of less than 5 g/L. O CH OH 30 O

O N 35 lst Ny OH It acts by inhibiting the body's production of prostaglan- HN N -O. dins (see U.S. Pat. No. 3,641,127 Rhone-Poulenc). (VI) Diclofenac is also a non-steroidal anti-inflammatory drug (NSAID) taken to reduce inflammation and as an One of the most commonly used antiviral drugs: it is pri analgesic reducing pain in certain conditions. 40 marily used for the treatment of herpes simplex W1US infections, as well as in the treatment of varicella Zoster (chickenpox) and herpes Zoster (shingles); see also U.S. C Pat. No. 4,199,574 (Wellcome). (IX) Imiquimod (3-(2-methylpropyl)-3,5,8-triazatricyclo 45 7.4.0.0. Itrideca-1 (9).2(6),4,7,10,12-hexaen-7-amine, NH INN) is a prescription medication that acts as an immune response modifier. C OH

O 50 NH2 N1 N N The name is derived from its chemical name: 2-(2,6- 2 y dichloranilino)phenylacetic acid. In the United King- ss N dom, India, Brazil and the United States, it may be Supplied as either the Sodium or potassium salt, in China \s, most often as the sodium salt, while in Some other coun tries only as the potassium salt. Diclofenac is available as a generic drug in a number of formulations. Over-the- 60. It is marketed by Meda AB, Graceway Pharmaceuticals counter (OTC) use is approved in some countries for and iNova Pharmaceuticals under the trade names minor aches and pains and fever associated with com Aldara and Zyclara, and by Mochida as Beselna. It is mon infections (see U.S. Pat. No. 3,558,690 Ciba also referred to as R-837 (see U.S. Pat. No. 4,689.338– Geigy). Riker). (VII) Metronidazole (2-(2-methyl-5-nitro-1H-imidazol-1- 65 (X) Terbinafine, more particularly terbinafine hydrochloride yl)ethanol) is a nitroimidazole antibiotic medication used (2E)-6,6-dimethylhept-2-en-4-yn-1-yl(methyl)(naph particularly for anaerobic bacteria and protozoa. thalen-1-ylmethyl)amine) is a synthetic allylamine anti US 9,125,936 B2 29 30 fungal from Novartis. It is highly lipophilic in nature and C nerve fibres, are preferably selected from the group con tends to accumulate in skin, nails, and fatty tissues. sisting of capsaicin and derivatives thereof. Vanillyl-nonyla mid and derivatives thereof, L-carnitine, coenzymA, isofla vonoides, soy extracts, ananas extract and conjugated CH3 linoleic acid. C. Fat Enhancing Agents CH3 Formulations and products according to the present inven 2 CH3 tion may also comprise one or more fat enhancing and/or adipogenic agents as well as agents enhancing or boosting the 10 activity of fat enhancing agents. A fat enhancing agent is for example hydroxymethoxy-phenyl propylmethylmethoxy benzofuran (trade name: Sym3DR). D. Hair Growth Activators or Inhibitors 15 Formulations and products according to the present inven It is sold by the name Lamisil in Argentina, Australia, tion may also comprise one or more hair growth activators, Belgium, Brazil, Canada, Chile, Egypt, Finland, France, i.e. agents to stimulate hair growth. Hairgrowth activators are Germany, Greece, Hungary, Iceland, Ireland, Israel, preferably selected from the group consisting of pyrimidine Mexico, Pakistan, Peru, New Zealand, Norway, Roma derivatives such as 2,4-diaminopyrimidine-3-oxide (Amin nia, Russia, Slovenia, South Africa, Sweden, United exil), 2,4-diamino-6-piperidinopyrimidine-3-oxide (Minoxi Kingdom, United States and Venezuela, also sold under dil) and derivatives thereof, 6-amino-1,2-dihydro-1-hydroxy the name Corbinal and Terbisil in Turkey and under the 2-imino-4-piperidinopyrimidine and its derivatives, Xanthine name “undofen cream” in Poland. As a generic it is sold alkaloids such as caffeine, theobromine and theophylline and under the name Zabel in Australia. It is also available as derivatives thereof, quercetin and derivatives, dihydroquerce a generic medication in the United States, United King 25 tin (taxifolin) and derivatives, potassium channel openers, dom, Belgium, Switzerland and Brazil. In India, Terbin antiandrogenic agents, synthetic or natural 5-reductase afine hydrochloride is available in topical form under the inhibitors, nicotinic acid esters such as tocopheryl nicotinate, brand name Sebifin (Ranbaxy Labs), Zimig (GSK benzyl nicotinate and C1-C6 alkyl nicotinate, proteins such as Pharma) and mycoCeaze (Progres Laboratories). My for example the tripeptide Lys-Pro-Val, diphencypren, hor coVa, developed by Apricus Biosciences, is a topical nail 30 mons, finasteride, dutasteride, flutamide, bicalutamide, preg solution ofterbinafine and DDAIP which has completed name derivatives, progesterone and its derivatives, cyproter three Phase III studies for the treatment of onychomy one acetate, spironolactone and other diuretics, calcineurin cosis (see U.S. Pat. No. 4,755,534 Sandoz) inhibitors such as FK506 (Tacrolimus, Fujimycin) and its (XI) Docosanol, also known as behenyl alcohol, is a saturated derivatives, Cyclosporin A and derivatives thereof, Zinc and fatty alcohol used traditionally as an emollient, emulsifier, 35 Zinc salts, polyphenols, procyanidins, proanthocyanidins, and thickener in cosmetics, nutritional Supplement (as an phytosterols such as for example beta-sitosterol, biotin, individual entity and also as a constituent of policosanol), eugenol, (t)-beta-citronellol, panthenol, glycogen for and more recently, in a Food and Drug Administration example from mussels, extracts from microorganisms, algae, (FDA) approved pharmaceutical, Abreva, approved as an plants and plant parts of for example the genera dandelion antiviral agent for reducing the duration of cold Sores 40 (Leontodon or Taraxacum), Orthosiphon, Vitex, Coffea, caused by the herpes simplex virus. Paullinia, Theobroma, Asiasarum, Cucurbita or Styphnolo (XII) Ciclopiroxolamine (6-cyclohexyl-1-hydroxy-4-meth bium, Serenoa repens (saw palmetto), Sophora flavescens, ylpyridin-2(1H)-one) also called Batrafen, Loprox. Pygeum africanum, Panicum miliaceum, Cimicifiiga race Mycoster, Penlac and StieproX, is a synthetic antifungal mosa, Glycine max, Eugenia Caryophyllata, Cotinus coggy agent for topical dermatologic treatment of Superficial 45 gria, Hibiscus rosa-simensis, Camelia sinensis, Ilex para mycoses. guariensis, Isochrysis galbana, licorice, grape, apple, barley or hops or/nd hydrolysates from rice or wheat. Alternatively, formulations and products according to the present invention may comprise one or more hair growth 50 inhibitors (as described above), i.e. agents to reduce or pre vent hair growth. Hair growth inhibitors are preferably selected from the group consisting of activin, activin deriva tives or activin agonists, ornithine decarboxylase inhibitors Such as alpha-difluoromethylornithine or pentacyclic triter 55 penes like for example ursolic acid, betulin, betulinic acid, oleanolic acid and derivatives thereof, 5alpha-reductase inhibitors, androgen receptor antagonists, S-adenosylme It is most useful against Tinea versicolor (see U.S. Pat. No. thionine decarboxylase inhibitors, gamma-glutamyl 3,883,545 Merck). transpeptidase inhibitors, transglutaminase inhibitors, soy B. Anti-Cellulite Agents 60 bean-derived serine protease inhibitors, extracts from micro Anti-cellulite agents and lipolytic agents are preferably organisms, algae, different microalgae or plants and plant selected from the group consisting of those described in WO parts of for example the families Leguminosae, Solanaceae, 2007/077541, and beta-adrenergic receptor agonists such as Graminae, Asclepiadaceae or Cucurbitaceae, the genera Synephrine and its derivatives, and cyclohexyl carbamates Chondrus, Gloiopeltis, Ceramium, Durvillea, Glycine max, described in WO 2010/097479. 65 Sanguisorba officinalis, Calendula officinalis, Hamamelis Agents enhancing or boosting the activity of anti-cellulite virginiana, Arnica montana, Salix alba, Hypericum perfora agents, in particular agents which stimulate and/or depolarise tum or Gymnema Sylvestre. US 9,125,936 B2 31 32 E. Solutes potassium citrate, potassium nitrate, potassium chloride, Formulations and products according to the present inven strontium chloride, hydrogen peroxide, aromas, sodium tion may also comprise one or more compatible solutes. Pre bicarbonate and/or odour correctants. ferred compatible solutes are such as described in WO Formulations or products according to the invention in the 01/76572, particularly dimyo-inositol phosphate (DIP), dig form of chewing gums or, in particular, dental care chewing lycerin phospate (DGP), di-myoinositol phosphate (DIP), gums comprise chewing gum bases which comprise elas cyclic 2.3 diphosphoglycerate (cDPG), 1,1-di-glycerol phos tomers, such as, for example, polyvinyl acetates (PVA), poly phate (DGP), beta-mannosylglycerate (firoin), beta-manno ethylenes, (low or medium molecular weight) polyisobutenes sylglyceramide (firoin-A) and dimannosyl-di-inositol phos (PIB), polybutadienes, isobutene-isoprene copolymers (butyl phate (DMIP) and ectoine and ectoine-derivatives, as 10 rubber), polyvinyl ethyl ethers (PVE), polyvinylbutyl ethers, described in EP 0553 884, EPO 671 161 and WO94/15923, copolymers of vinyl esters and vinyl ethers, styrene/butadi in particular (S)-1,4,5,6-tetrahydro-2-methyl-4-pyrimidin ene copolymers (styrene/butadiene rubber, SBR) or vinyl ecarboxylic acid) and hydroxyectoine ((S,S)-1,4,5,6-tetrahy elastomers, e.g. based on vinyl acetate/vinyl laurate, vinyl dro-5-hydroxy-2-methyl-4-pyrinnidinecarboxylic acid). acetate/vinyl Stearate or ethylene/vinyl acetate, and mixtures Preferably, the total amount of compatible solutes is in the 15 of the elastomers mentioned, as described, for example, in EP range of from 0.05 to 10 wt.-%, preferably from 0.1 to 5 O 242325, U.S. Pat. No. 4,518,615, U.S. Pat. No. 5,093,136, wt.-%, based on the total weight of the formulation or prod U.S. Pat. No. 5,266,336 U.S. Pat. No. 5,601,858 or U.S. Pat. uct. No. 6,986,709. In addition, chewing gum bases comprise F. Solvents further constituents, such as, for example, Sugars, Sugar Sub The pharmaceutical compositions may contain Such as for stitutes or Sweet-tasting Substances in particular those example aliphatic alcohols or 1.2-alkandiols or of course described in WO 2009/21558, (mineral) fillers, plasticizers, simply water. Suitable aliphatic alcohols are selected from the emulsifiers, antioxidants, waxes, fats or fatty oils, such as, for group consisting of ethanol, n-propanol, isopropylalcohol, example, hardened (hydrogenated) plant or animal fats, and the isomeric butanols and their mixtures. The preferred spe mono-, di- or triglycerides. Suitable (mineral) fillers are, for cies is ethanol, in particular with a purity of at least 95%. 25 example, calcium carbonate, titanium dioxide, silicon diox Suitable 1,2-alkandiols encompass 1.2-butadiol. 1.2-pentan ide, talc, aluminium oxide, dicalcium phosphate, tricalcium diol. 1.2-hexandiol. 1.2-heptanddiol. 1.2-octandiol. 1.2- phosphate, magnesium hydroxide and mixtures thereof. Suit nonandiol. 1,2-decandiol. 1.2-undecandiol. 1.2.dodecandiol able plasticizers or agents for preventing Sticking (detackifi and their mixtures. The preferred 1,2-alkandiol is 1.2-pentan ers) are, for example, lanolin, Stearic acid, sodium Stearate, diol. 30 ethyl acetate, diacetin (glycerol diacetate), triacetin (glycerol Oral Compositions triacetate) and triethyl citrate. Suitable waxes are, for Another embodiment of the present invention refers to an example, paraffin waxes, candelilla wax, carnauba wax, oral composition comprising the new ginger extract, contain microcrystalline waxes and polyethylene waxes. Suitable ing the extract in an amount of from about 0.01 to about 1, emulsifiers are, for example, phosphatides, such as lecithin, preferably from about 0.1 to about 0.5% b.w.—calculated on 35 and mono- and diglycerides of fatty acids, e.g. glycerol the total composition. Oral compositions are intended to be mono Stearate. brought into contact with the oral cavity, for example in the Formulations or products according to the invention (in form of toothpastes, dental gels, dental creams, mouth particular those which are in the form of an oral care formu washes, Sugar-free candies for Sucking, oral sprays, dental lation or product or in the form of a formulation) preferably floss or dental care chewing gums. That is why they are also 40 additionally comprise one or more aroma and/or flavouring considered to be dental compositions. The term does not Substances, such as essential oils and extracts, tinctures and encompass food products dedicated for nutrition. balsams, such as, for example, anisole, basil oil, bergamotoil, The oral compositions of the present invention typically bitter almond oil, camphor oil, citronella oil, lemon oil: Euca comprise an abrasive system (abrasive or polishing agent), lyptus citriodora oil, eucalyptus oil, fennel oil, grapefruit oil, Such as e.g. silicas, calcium carbonates, calcium phosphates, 45 camomile oil, spearmint oil, caraway oil, lime oil, mandarin aluminium oxides and/or hydroxyapatites, Surface-active oil, nutmeg oil (in particular nutmeg blossom oil-maces oil, Substances, such as e.g. sodium lauryl Sulfate, Sodium lauryl mace oil), myrrh oil, clove oil, clove blossom oil, orange oil, sarcosinate and/or cocamidopropyl betaine, moisture-retain oregano oil, parsley (seed) oil, peppermint oil, rosemary oil, ing agents, such as e.g. glycerol and/or Sorbitol, thickening sage oil (clary sage, Dalmatian or Spanish sage oil), Star agents, such as e.g. carboxymethylcellulose, polyethylene 50 aniseed oil, thyme oil, Vanilla extract.juniper oil (in particular glycols, carrageenan and/or Laponite R, Sweeteners, such as juniper berry oil), wintergreen oil, cinnamon leaf oil; cinna e.g. saccharin, flavour correctants for unpleasant taste mon bark oil, and fractions thereof, or constituents isolated impressions, flavour correctants for further, as a rule not therefrom. unpleasant taste impressions, flavour-modulating Substances It is of particular advantage if said formulations or products (e.g. inositol phosphate, nucleotides, such as guanosine 55 comprise at least one aroma Substance, preferably 2, 3, 4, 5, 6, monophosphate, adenosine monophosphate or other Sub 7, 8, 9, 10 or more aroma substances, chosen from the fol stances, such as Sodium glutamate or 2-phenoxypropionic lowing group: menthol (preferably I-menthol and/or racemic acid), cooling active compounds, such as e.g. mentholderiva menthol), anethole, anisole, anisaldehyde, anisyl alcohol, (ra tives (e.g. L-menthyl lactate, L-menthyl alkyl carbonates, cemic) neomenthol, eucalyptol (1,8-cineol), menthone (pref menthone ketals, menthanecarboxylic acid amides), 2.2.2- 60 erably L-menthone), isomenthone (preferably D-isomen trialkylacetic acid amides (e.g. 2,2-diisopropylpropionic acid thone), isopulegol, menthyl acetate (preferably L-menthyl methylamide), icilin and icilin derivatives, stabilizers and acetate), menthyl propionate, carvone (preferably (-)-car active compounds, such as e.g. sodium fluoride, sodium vone, optionally as a constituent of a spearmint oil), methyl monofluorophosphate, tin difluoride, quaternary ammonium salicylate (optionally as a constituent of a wintergreen oil), fluorides, Zinc citrate, Zinc sulfate, tin pyrophosphate, tin 65 eugenol acetate, isoeugenol methyl ether, beta-homocycloci dichloride, mixtures of various pyrophosphates, triclosan, tral, eugenol, isobutyraldehyde, 3-octanol, dimethyl sulfide, chlorhexidine, cetylpyridinium chloride, aluminium lactate, hexanol, hexanal, trans-2-hexenal, cis-3-hexenol, 4-terpin US 9,125,936 B2 33 34 eol, piperitone, linalool, 8-ocimenyl acetate, isoamyl alcohol, TABLE 1 isovaleraldehyde, alpha-pinene, beta-pinene, linnonene (preferably D-linnonene, optionally as a constituent of an Composition of a ginger extract according essential oil), piperitone, trans-Sabinene hydrate, menthofu to the invention (content in % b.w. ran, caryophyllene, germacrene D, cinnamaldehyde, mint Component Average content Specification lactone, thymol, gamma-octalactone, gamma-nonalactone, 6-gingerol 27 25-30 gamma-decalactone, (1.3E.5Z)-undecatriene, 2-butanone, 8-gingerol 7 S-10 ethyl formate, 3-octyl acetate, isoamyl isovalerate, cis- and 10-gingerol 7 S-10 trans-carvyl acetate, p-cymol, damascenone, damascone, cis 10 Sum of gingerols 41 35-50 rose oxide, trans-rose oxide, fenchol, acetaldehyde diethyl 6-shogaol 2.5 15-4 acetal, 1-ethoxyethyl acetate, cis-4-heptenal, cis-jasmone, 8-Shogaol 1 O3-13 methyl dihydrojasmonate, 2'-hydroxypropiophenone, men 10-shogaol O.2 O.O3-1 thyl methyl ether, myrtenyl acetate, 2-phenylethyl alcohol, Sum of shogaols 3.7 less than 6 2-phenylethyl isobutyrate, 2-phenylethyl isovalerate, 15 Zingerone O.OS less than 1 geraniol, nerol and viridiflorol. Sum of pungent components 45 42-50 Medicaments As shown in the experimental part, the new extracts show various Surprising activities with regard to stem cell protec Example 2 tion, anti-oxidation and anti-inflammation. Therefore, another object of the present invention is directed to a medi Stem Cell Protection cament comprising the new ginger extract for protecting stem cells and for inhibiting the cyclooxygenase-2 (COX-2) activ In Vitro ity and prostaglandin ES release. 25 HHFSC (Human Hair Follicle Stem Cells) isolated from hair follicle bulge (Celprogen) were cultivated in culture ware INDUSTRIAL APPLICATION pre-coated with Human Hair Follicle Stem Cell Extra-cellu lar Matrix (Celprogen). The cells were incubated 2 h prior to Another object of the present invention is a therapeutical 30 and 16 h after UVB irradiation with test compounds. Cells method for preserving stem cells by oral administration of a were irradiated with 25 ml/cm UVB in the presence ofbuffer working amount of the ginger extract of claim 1 to an indi solution. Apoptosis induction was evaluated by caspase 3/7 vidual. protein expression (Caspase-Glo 3/7. Promega) and quanti Another object of the present invention is also a non-thera fied by chemiluminescence measurement. peutical method for preserving stem cells by topical admin 35 The inhibition of apoptosis induction in the presence oftest istration of a working amount of the extract of claim 1 to skin Substances was calculated according to the following equa or hair of an individual. tion: Finally, additional embodiments of the present invention are directed to the use of the new ginger extracts 40 Inhibition of apoptosis induction% = as a protection agents for stem cells. RLU test substance - RLU control without UWB as an anti-oxidants. 100- RLU control - RLU control without UWB x 100) as anti-inflammation agents. The abbreviations have the following meanings: as an anti-aging agents, particularly for skin and hair. 45 RLU test substance: RLU of the wells with test substance and with UVB irra diation EXAMPLES RLU control: RLU of the wells without test Substance, but with UVB Example 1 50 irradiation RLU control without UVB: RLU of the wells without test substance and without UVB Fresh ginger roots were frozen at -18°C. and afterwards irradiation shredded and cut. This material was dried at 30° C. for 17 The results are shown in Table 2: hours using a continuous flow dryer. The dried material was 55 subjected to supercritical extraction with carbon dioxide at TABLE 2 35° C., 250 bar and a flow rate of 10 kg CO/hkg raw material. A first fraction collected within the first three hours Inhibition of apoptosis induction relative to control of the extraction process was discarded due to the high con Concentration Inhibition of UV in tent of essential oil. A second fraction from 3 hours to 5 hours 60 Test Substance % b.w. duced apoptosis 96 from the starting was collected after de-pressurizing process Ginger pungent CO2 O.OOOS 2O2 resulting in the ginger extract according to the present inven extract (50% plungent components) tion. 32 kg dried ginger root resulted in 1 kg ginger extract Ginger CO extract O.OO2 22.6 (30% pungent components) according to the invention. 65 Ginger Hexan Isopropanol O.OO2 18.0 The composition of the extract thus obtained is presented in 8:2 extract Table 1. FIG. 1 shows a HPLC chromatogram of the extract. US 9,125,936 B2 35 36 TABLE 2-continued Example 4 Inhibition of apoptosis induction relative to control PGE2 Assay Concentration Inhibition of UV in Test Substance % b.w. duced apoptosis 96 5 Ginger ethanol/water O.OO2 18.4 In Vitro 1:1 extract Ginger water extract O.OO2 12.4 Normal human epidermal keratinocytes (Lonza) are 10 seeded in a 96-well microtiter plate at a concentration of Due to the lower concentration the ginger extract according 1.2x10 cells/well. Incubation for 20 to 24h takes place at 37° to the present invention is the most potent inhibitor of UV C., 5% CO2, saturated humidity until growth to 50-60% induced apoptosis. confluency. Various concentrations of the test Substances are applied to the cells in culture media. After incubation for 30 Example 3 15 min the stimulation with 1 uM A23 187 Calcium lonophor (except for an unstimulated control) is started. After another 30 min of incubation, 50 uL of the supernatants are taken for COX-2-Assay the quantification of PGE2 using the competitive ELISA (PGE2 Biotrak EIA System, RPN222, Fa. GE Healthcare). In Vitro The percent bound for each standard and unknown sub stance is calculated using the following equation: Cyclooxygenase-2 (COX-2) in the presence of test sub stance was mixed with the fluorometric substrate 10-acetyl Astandard or test substance Ablank 3,7-dihydroxyphenoxanin (ADHP) and Heme. The reaction % Bf Bo = x 100 was started by addition of the substrate arachidonic acid. 25 Azero standard - Ablank COX-2 converted the arachidonic acid into the prostaglan din endoperoxide G2 (PGG2). PGG2 was reduced to the corresponding alcohol PGH2. During this reaction ADHP The abbreviations have the following meanings: resulted in fluorescent resorufin. Resorufin was quantified at 30 A(standard or test Substance): an extinction wavelength of 535 nm and an emission wave Absorption of the wells with standard or test substance length of 590 nm. A(zero standard): The inhibition of COX-2 activity in the presence of test Substances was calculated according to the following equa Absorption of the wells without PGE standard tion: 35 A(blank): Absorption of the wells without antibody, without peroxi dase conjugate Inhibition of COX-2 % = 100 A standard curve is generated by plotting the percent B/B0 test substance - Resorufin control without COX-2 as a function of the log PGE2 concentration. The PGE2 x 100 40 amount in the unknown samples is calculated by interpolating Resorufin control - Resorufin control without COX-2 from the percent B/B0 values to PGE2 concentrations. The inhibition of the biosynthesis of PGE2 in the presence The abbreviations have the following meanings: of test Substances is calculated according to the following Resorufin test substance: 45 equation: Resorufin concentration of the wells with test substance and with COX-2 Inhibition of PGE2 % = Resorufin control: PGE2test substance - PGE2without cells Resorufin concentration of the wells without test Sub 50 100- ( stance, but with COX-2 PGE2control - PGE2ithout cells x100) Resorufin control without COX-2: Resorufin concentration of the wells without test substance The abbreviations have the following meanings: and without COX-2 PGE2 test substance: From the inhibition of the COX-2 % in a series of dilu 55 Amount of PGE2 of the wells with test substance and with tions of tested samples the IC50 was calculated. This was the cells concentration at which the activity of the COX-2 was inhib PGE2 control: ited by 50%. The results are shown in Table 3: Amount of PGE2 of the wells without test substance, but TABLE 3 60 with cells PGE2 without cells COX-2 inhibition (nean value of at least 2 independent tests Amount of PGE2 of the wells without cells Test Substance ICso The IC50 is calculated from the inhibition of PGE2 release Ginger extract BIO3040 O.OOOS90 65 % in a series of dilutions of tested samples. This is the concentrations at which the biosynthesis of PGE2 is inhibited 50%. The results are shown in Table 4. US 9,125,936 B2 37 38 TABLE 4 An increased level of ROS (reactive oxygen species) led to an increased amount of fluorescence. PGE2 Inhibition (mean value of at least 2 independent tests The inhibition of the oxidation in the presence of test Test Substance IC50 Substances was calculated according to the following equa 5 tion: Ginger extract BIO3040 O.OOO20% O.OOOO5%

Inhibition of oxidation% = Example 5 RFU test substance - RFUwithoutcells 10 100 X 100) ABTS-Assay ( RFUcontrol - RFUwithoutcells

In Vitro The abbreviations have the following meanings: RFU test substance: With the help of the ABTS-assay the anti-oxidative capac 15 Relative fluorescence units of the wells with test substance ity of test Substances was measured. 2,2'-azino bis-(3-ethyl and with cells benzothiazoline 6-sulfonic acid) (ABTS) was transformed by RFU control: potassium persulfate into the blue-green radical cation Relative fluorescence units of the wells without test Sub ABTS+. Through the addition of anti-oxidants (test sub stance, but with cells stances) the radical cations were reduced and discoloration RFU without cells: took place, which was determined photometrically at 734 nm. Relative fluorescence units of the wells without test Sub stance and without cells (blank) The IC50 was calculated from the inhibition% in a series A test substance 25 of dilutions of tested samples. This is the concentration at Inhibition% = 100- ( A control X 100) which the oxidation is 50% inhibited. The results are shown in Table 6: The abbreviations have the following meanings: A test Substance: TABLE 6 30 Absorption of the wells with test substance Activity based on the inhibition of oxidation A control: mean value from at least 2 independent tests Absorption of the wells without test substance Concentration Intracellular ROS From the inhibition of the radical formation% in a series Test Substance % b.w. reduction 96 of dilutions of tested samples the IC50 was calculated. This is 35 Ginger pungent CO2 extract O.OOOS 60 the concentration at which the radical formation is inhibited (50% pungent components) by 50%. The results are shown in Table 5: Ginger CO extract O.OOOS 47 (30% pungent components) TABLE 5 Ginger Hexan Isopropanol O.OOOS 49 8:2 extract 40 Ginger ethanol/water O.OOOS 32 Activity based on the inhibition of radical formation 1:1 extract mean value from at least 2 independent tests Ginger water extract O.OOOS 22 Test Substance ICso (ppm) Ginger extract BIO3040 12 The ginger extract according to the present invention is the 45 extract with the highestanti-oxidative capacity in DCF assay. Example 7 Example 6 Heme Oxygenase-1 Expression DCF Assay 50 In Vitro In Vitro NHDF (normal human dermal fibroblasts) cells were dis Primary human dermal fibroblasts (Lonza) were seeded in seminated in a 6-well plate in a concentration of 2x10 cells/ a 96-well microtiter plate at a concentration of 0.5x10" cells/ 55 well (DMEM, 10% FCS). After cultivation in fully enriched well. Cultivation took place at 37° C. and 5% CO, in DMEM, medium (DMEM, 10% FCS) for 48 h at 37° C. and 5% CO2, enriched with 10% foetal calf serum. Confluence was sup the serum content was reduced to 0.1% to synchronize the cell posed to be around 70% at the time, the incubation with the cycle. Various concentrations of the test Substances, the nega test Substances began. Various concentrations of the test Sub tive control (untreated cells) and tert-butylhydrochinon as stances were applied to the cells in DMEM. After 24 h of 60 positive control, are added and incubated for a further 24 h. incubation, 100 uL HDCF-DA-solution (10 uM) incl. DAPI The maximum concentration of the test Substances used cor (1:1000) was added to all samples (excluded the background responds to 0.2 times the value of the IC20 value of the control) and incubated for one hour to deesterify the HDCF cytotoxicity assay. After cell lysis, the protein amount was DA by cellular esterases. The resulting HDCF was thereby determined using the Biorad BCA assay. All samples were trapped inside the cell. After the incubation, the cells were 65 adjusted to the same protein level before application on a fast washed and the prooxidant challenge was set (1 mM, 1 h). The Criterion Gel (Biorad) to perform electrophoresis for 20 min resulting fluorescence was read at WeX 504 nm, Wem 524 nm. utes at 300 V. Thereafter the proteins were transferred to a US 9,125,936 B2 39 40 PVDF membrane on a semi-dry blotter (30 minutes, 25 V). The blotted membrane is blocked for 4 hours in a 5% milk Atest substance - HAwithout cells powder solution in TBST at 4°C. After washing, the mem Induction of HA 96 = ( HA control - HAwithout cells X 100) brane is incubated with the first antibody solution HO-1 from abcam (1:500 in 1% milk powder in TBST) over night. After 5 The abbreviations have the following meanings: this, washing is repeated and the membrane has to be incu HA test substance: bated for 1 h in the second antibody solution (goat anti mouse Amount of HA of the wells with test substance and with coupled to HRP; 1:800 in 1% milk powder). After washing, cells the membrane is exposed to chemiluminescence HRP-Sub 10 HA control: strate solution for 5 minutes. The resulting band pattern is Amount of HA of the wells without test substance, but with detected with a chemiluminescence sensitive camera system cells (Vilber Lou mat). The quantification was done by densitom HA without cells etry, using the Image J freeware software. The results are Amount of HA of the wells without cells shown in Table 7: 15 The results are shown in Table 8: TABLE 7 TABLE 8 HO-1 up-regulation relative to control Hyaluronic acid stimulation relative to control Concentration Concentration Test Substance % b.w. Up-regulation Test Substance % b.w. Stimulation Ginger extract BIO3040 O.OOO5% 34-fold Ginger extract BIO3040 O.OOOO1.75% 67.3% O.OOOO35% 34.4% O.OOOO7% 21.3% 25 Example 8 Formulation Examples for Skin Care Products Hyaluronic Acid Assay 9–Skin-lightening day care fluid O/W 30 10–Shaving Cream O/W In Vitro 11=After shave hydrogel 12=After-Sun spray O/W 13=Sunscreen lotion (O/W), broad-band protection NHDF (normal human dermal fibroblasts) cells were dis 14=W/O night cream seminated in a 96-well microtiter plate in a concentration of 35 15=Barrier repair cream O/W 2x10 cells/well (DMEM, 10% FCS). After cultivation in 16-Calming Balm fully enriched medium (DMEM, 10% FCS) for 48 hat 37° C. 17 Antiperspirant pump spray and 5% CO2, the serum content was reduced to 0.1% to 18–Body Wash synchronize the cell cycle. Various concentrations of the test 19–Body Oil Substances and TGF-beta1 as internal standard are added and 40 20=Anti-Cellulite Balm incubated for a further 72 h. The maximum concentration of In Examples the following two perfume oils PFO1 and the test substances used corresponds to 0.2 times the value of PFO2 were each used as fragrance (DPG 0 dipropylene gly the IC20 value of the cytotoxicity assay. Hyaluronic acid is quantified by a competitive ELISA (TE-COmedical col). TE1017). 45 TABLE I The percent bound for each standard and unknown sub stance is calculated using the following equation: Perfume oil. PFO1 with rose Smell Component?Name Parts b.w. Acetophenone, 10% in DPG 1O.OO HA ng/ml = Astandard or test substance - Ablank 50 gf Azero standard - Ablank n-Undecanal S.OO Aldehyde C14, so-called (peach aldehyde) 1S.OO Allylamylglycolate, 10% in DPG 2O.OO Amyl Salicylate 2S.OO The abbreviations have the following meanings: Benzyl acetate 60.00 Citronellol 8O.OO A(standard or test Substance): 55 d-Limonene SO.OO Absorption of the wells with standard or test substance Decenol trans-9 1S.OO Dihydromyrcenol SO.OO A(Zero standard): Dimethylbenzylcarbinyl acetate 30.00 Diphenyloxide S.OO Absorption of the wells without HA standard Eucalyptol 1O.OO A(blank): 60 Geraniol 40.00 Nerol 2O.OO Absorption of the wells without antibody, without peroxi Geranium oil 1S.OO dase conjugate Hexenol cis-3, 10% in DPG S.OO Hexenyl salicylate cis-3 2O.OO A standard curve is generated by plotting the percent B/B0 indole, 10% in DPG 1O.OO as a function of the log HA concentration. The HA amount in 65 Alpha-ionone 1S.OO the unknown samples is calculated by interpolating from the Beta-ionone S.OO percent B/B0 values to PGE2 concentrations. US 9,125,936 B2 41 42 TABLE I-continued TABLE II-continued

Perfume oil. PFO1 with rose Smell Perfume oil. PFO1 with rose Smell Component?Name Parts b.w. 5 Component?Name Parts b.w. Lilial (R) (2-methyl-3-(4-tert-butyl-phenyl)propanal) 6O.OO Globanone (R) 18O.OO Linalool 40.OO (E,Z)-8-cyclohexadecen-1-one Methylphenyl acetate 1O.OO Hedione (R) 140.00 Phenylethyl alcohol 275.00 (methyldihydrolasmonate) Styrolyl acetate 2O.OO Hexenyl salicylate, cis-3 10.00 Terpineol 3O.OO 10 Vertocitral S.OO Tetrahydrolinalool SO.OO (2,4-dimethyl-3-cyclohexenecarboxaldehyde) Cinnamyl alcohol 1O.OO Hydratropaaldehyde, 10% in DPG S.OO Sodamascone S.OO Total: 1,000.00 (1-(2,4,4-trimethyl-2-cyclohexen-1-yl)-2-buten-1-one, O% in DPG 15 Isomuscone (cyclohexadecanone) 40.00 acinthaflor (2-methyl-4-phenyl-1,3-dioxolane) 10.00 TABLE II Cis-jasmone, 10% in DPG 2O.OO Linalool SO.OO Perfume oil. PFO1 with rose Smell Linallyl acetate 30.00 Methylbenzoate, 10% in DPG 25.00 Component?Name Parts b.w. 20 para-Methylcresol, 10% in DPG 10.00 Benzyl acetate 6O.OO R 2O.OO Citronellyl acetate 6O.OO enylpropylaldehyde S.OO Cyclamenaldehyde 2O.OO 2-Phenylethyl alcohol 82.OO (2-methyl-3-(4-isopropylphenyl)propanal Tetrahydrogeraniol 13.00 Dipropylene glycol (DPG) 6O.OO 2,2-Dimethyl-3-cyclohexyl-1-propanol 80.00 Ethyllinalool 40.OO 25 Florol 30.00 Total: 1,000.00 (2-isobutyl-4-methyltetrahydro-2H-pyran-4-ol)

TABLE III Skin care compositions

Component/INCI 9 10 11 12 13 14 15 16 17 18 19 2O Ginger extract acc. O.OS O-1 O1 O.25 O1. O.15 0.1 O.2 O.O3 O.2 0.15 0.08 Invention Alpha-Bisabol 0.4 O.1 O.1 Dimethicone O.S O.S 2.0 3.0 Abi 350 Allantoin O.1 O.1 Aloe Vera Gel 1.O 3.0 Concentrate Aluminium Stearate 1.O Alugel 34TH Beta-Arbutin 1.O Laureth-2 Arlypon F Avocado oil 3.0 2.O Caffeine pure 1.O Carbomer O.2 O.2 Carbopol ETD Acrylates/C10-30 Alkyl 0.4 O.6 Acrylate Crosspolamer Carbopol Ultrez 21 Cetylhydroxyproline O.S palmitamide CeramideBio Hydroxyethyl Palmityl O.1 Oxyhydroxypropyl Palmitamide Ceramide SL Citric Acid O.3 O.2 Cocamide MEA O.S Comperlan 100 Tocopherol — 0.1 — 0.2 Cowi-Ox T-70 Cyclohexasiloxane, — 2.0 2.0 Cyclopentasiloxane Panthenol OS 1.0 1.O Glyceryl Stearate Citrate 1.5 Glyceryl Stearate 2.O Acrylates/C10-30 Alkyl 0.4 O.6 Acrylate Crosspolymer US 9,125,936 B2 43 44 TABLE III-continued Skin care compositions

Component/INCI 9 10 11 12 13 14 15 16 17 18 19 Cetylhydroxypro-line Palmitamide Hydroxyethyl Palmityl Oxyhydroxypropyl Palmitamide Citric Aci Cocamide MEA Tocophero — 0.1 Cyclohexasiloxane, — 2.0 2.0 Cyclopentasiloxane Panthenol O.S. O.1 1.O Glyceryl Stearate Citrate Dracorin CE Glyceryl Stearate 2.O Dracorin GMS Glyceryl Oleate Citrate, Caprylic Capric Triglyceride Dracorin GOC Phenoxyethanol, Methyl 0.4 paraben, Ethylparaben, Butylparaben, Propyl paraben, Sobutylparaben Dragocid Liquid Glycerin, Triticum 1.O Vulgare (Wheat) Gluten, Water (Aqua) Dragoderm Polyglyceryl-3-Polyricino eate, Sorbitanisostearate Dragonsan WO Liquid Sorbitan Isostearate, Hydrogenated Castor Oil, Ceresin, Beeswax Dragosan WOP Bisabolol Ethylhexyl 2.O Ethylisononanoate Dragoxat 89 Stearic Acid, Palmitic Acid 24.0 Edenor L2 Coconut-Palmkernel Oil Fatty Acid Edenor K12-18 Tetrasodium EDTA Disodium EDTA O.1 O.1 Potassium Cetyl Phos phate, Hydrogenated Palm Glycerides Emulsiphos Ethanol 1.O Water (Aqua), Propylene 1.O Glycol, Paulinia Cupana Seed Extract, Alcohol Extrapone Guarana Propylene Glycol, Hamamelis Virginiana (Witch Hazel) Water, Water (Aqua), Hamamelis Virginiana (Witch Hazel) Extract Extrapone Witch Hazel Glycerin, Water (Aqua), Rosmarinus officinalis (Rosemary) Leaf Extract Extrapone Rosemary GW Water (Aqua), Propylene 2.5 Glycol, Potassium Iodide, Fucus Vesiculosus Extract Extrapone Seaweed Fragrance PFO I, II O.3 1.O 0.4 Menthone Glycerin Acetal Frecolat MGA US 9,125,936 B2 45 46 TABLE III-continued Skin care compositions

Component/INCI 9 10 11 12 13 14 15 16 17 18 19 2O Menthyl Lactate O3 O.S 3.0 — Frescolat ML Sodium Laureth Sulfate 37.O - Genapol LRO Zinc Gluconate 0.5 — Givobio GZN Glycerin 3.5 2.3 - 4.7 4.7 2.0 3.0 1.7 Pentylene Glycol S.O S.O 3.0 5.0 — Water, Pentylene Glycol, 1.0 — 1.0 — Glycerin, Sodium Lactate, Lactic Acid, Serine, Urea, Sorbitol, Sodium Chloride, Allantoin Hydrolite-5 Diisopropyl Adipate 2.0 Trisononanoin 3.0 1.O — 10.0 — Sorbitol 2.0 — Xanthan Gum 0.2 — O.2 Kojic Acid O.S Cetyl Alcohol 1.5 — 1.0 — 2.0 — Cetearyl Alcohol Aluminium 16.0 Chlorohydrate Macadamia Ternifolia 0.5 — Seed Oil Magnesium Chloride 0.7 — Polyguaternium-7 0.5 — Paraffinum Liquidum 52.5 - Butyl Methoxy-dibenzoyl- 2.0 — 1.O methane Neo Heliopan 357 Disodium Phenyl – 10.0

Tetrasulfonate Neo Heliopan AP Ethylhexyl Methoxy- 7.5 3.0 cinnamate Neo Heliopan AV Benzophenone-3 3.0 Neo Heliopan BB Phenylbenzimidazole 6.7 Sulfonic Acid Neo Heliopan Hydro Homosalate 1O.O Neo Heliopan HMS 4-Methylbenzyl-idene 1.5 Camphor Neo Heliopan MBC Ethylhexyl Salicylate 5.0 — S.O Neo Heliopan OS Trideceth-9, PEG-5 1.O 2.O Ethylhexanoate, Water Neo PLC Water Soluble Caprylic Capric 3.0 - S.O 2.0 — 10.0 — Triglyceride BHT 0.1 — Diethylhexyl 0.5 — Syringylidene Malonate) Oxynex 204 PEG-26 Jojoba Acid, PEG- 1.O 26 Jojoba Alcohol Oxypon 328 Cetearyl Ethylhexoate — 4.0 3.0 — 21.0 — PCL Liquid Stearyl Heptanoate, — 0.5 1.O Stearyl Caprylate PCL Solid Cetearyl Ethylhexanoate, — 12.5 — sopropyl Myristate PCL Liquid Acrylates/C10-30 Alkyl - O.25 Acrylate Crosspolymer Pemulen TR-2 Shea Butter 0.5 — Potassium Hydroxide — 11.0 Potassium Sorbate — 0.1 US 9,125,936 B2 47 48 TABLE III-continued Skin care compositions

Component/INCI 9 10 11 12 13 14 15 16 17 18 19 2O Propylene Glycol S.O 3.0 2.0 Retinyl Palmitate O.2 — 0.05 — Polyacrylamide, C 13-14 2.0 Isoparaffin, Laureth-7 Sepigel 305 Sodium Ascorbyl 1.O Phosphate Sodium Benzoate O.S Sodium Chloride 1.O Sodium Hydroxide 1.O Sodium Hydroxide O.2 0.7 O.3 1.O PEG-40 Hydrogenated 1.5 3.0 Castor Oil, Trideceth-9, Water (Aqua) Heianthus Annuus — 5.0 (Sunflower) Seed Oil Prunus dulcis — 5.0 Hydroxymethoxyphenyl — 0.25 — Propylmethylmethoxy benzofuran

Butylene Glycol, O.2 1.O Pentylene Glycol, Hydroxyphenyl Propamidobenzoic Acid SymCalmin Dimethyl Phenyl 2- O.S Butanol SymDeo MPP 2-Hexanediol, Caprylyl 1.O — 1.0

Trimethylcyclohexyl O.1 Butylcarbamate SymFit 1617 Water (Aqua), Glycerin, 1.O Beta-Glucan SymClucan Benzylidene Dimethoxy- O.1 dimethylindanone SymHelios Maltodextrin, Rubus O2 1.0 Fruticosus (Blackberry) Leaf Extract SymMatrix Trideceth-9, PEG-5 1.O Isononanoate, Water SymMollient WIS Glycerin, Water (Aqua), S.O Myristoyl Pentapeptide-8 SymPeptie 222 Bisabolol, Zingiber O.1 Officinale Root Extract SymRelief 100 Bisabolol, O.1 O.1 Hydroxymethoxyphenyl Decanone SymRelief S Hexyldecanol, Bisabolol, 1.O Cetylhydroxyproline Palmitamide, Stearic Acid, Brassica Campestris (Rapeseed) Sterols SymRepair Aloe Barbadensis O.1 O.S SymVital Phenylethyl Resorcinol O.S SymWhite 377 Talcum 3.0 Phytosterols O.3 Water Ad 100 US 9,125,936 B2 49 50 Formulation Examples for Hair Care Products 25-Hair Setting Gel 26–Pump Hair Spray with UV Protection 21=Clear shampoo 22=Pearlized Conditioner Shampoo 27=Hair Ends Fluid without Silicon Oil 23=Hair Conditioner, Leave on 28=Anti-Dandruff Hair Tonic 24=Hair Conditioner, Rinse off 29=Aerosol Hair Spray TABLE IV

Hair care formulations

Component/INCI 21 22 23 24 25 26 27 28 29 Zingiber Officinale (Ginger) Root Extract O.2 O.OS O.OS 0.1 O.1 O.OS Water (Aqua), Butylene Glycol, Malic Acid, 1.O Actinidia Chinensis (Kiwi) Fruit Juice, Citrus Aurantium Dulcis (Orange) Juice, Citrus Paradisi (Grapefruit) Juice, Pyrus Maius (Apple) Juice, Trideceth-9, Prunus Amygdalus Dulcis (Sweet Almond) Seed Extract Actipone Alpha Pulp Aminomethylpropanol 0.7 Propylene Glycol, PEG-55 Propylene Glycol Distearate Antil 141 Liquid PEG-200 Hydrogenated Glyceryl Palmitate, PEG-7 1.5 Glyceryl Cocoate Antil 200 Carbomer 0.7 Carbopol ETD 2001 Citric aci Vincylcaprolactam?VP/Dimethylaminoethyl methacrylate Copolymer Copolymer VC 713 Climbazole O.1 Criniipan AD Cetrimonium Chloride 1.O 4.O Dehyguart A CA Cocoamidopropyl Betaine 8.0 Dehyton K Panthenol 1.O 1.O Water (Aqua), Glycerin, Avena Saiva (Oat) Kernel Extract DragoCalm Bisabolol Dragosantol Glycerin, Triticum Vulgare (Wheat) Gluten, 2.O Water Dragoderm Ethanol 84.O. 18.O 39.0 35.8 Glycol Distearate, Laureth-4, Cocoamidopropyl Betaine Euperlan PK 4000 Water (Aqua), Glycerin, Wine Extract, Alcohol Extrapone Champagne GW Menthyl Lactate FrescolatML Menthyl Ethylamido Oxalate FrescolatX-Cool Sodium Laureth Sulfate Generol LRO liquid Glycerin Cetyl Alcohol, Behentrimonium Chloride, Triticum Vulgare (Wheat) Bran Extract, Linoleic Acid Water (Aqua), Pentylene Glycol, Glycerin, 1.O Fructose, Urea, Citric Acid, Sodium Hydroxide, Maltose, Sodium PCA, Sodium Chloride, Sodium Lactate, Trehalose, Allantoin, Sodium Hyaluronate, Hydroviton Plus 2290 Cetearyl Octanoate Cetearyl Alcohol Lanette O PVP 3.0 Luviskol K30 Powder PVP/VA Copolymer Luwiskol VA37 E Polyguaterinium-7 Merquat 550 C12-15 Pareth-12 4.0 Mulsifan RT203.80 US 9,125,936 B2 51 52 TABLE IV-continued

Hair care formulations

Component/INCI 21 22 23 24 25 26 27 28 29 Hydroxyethylcellulose O.6 Notrosol 25OHHR Maltodextrin, Aspalathus Linearis Leaf Extract O.1 NeoActipone Benzophenone-3 O.3 O.2 O.2 Neo Heliopan BB Phenylbenzimidazole Sulfonic Acid O.2 Neo Heliopan Hydro Trideceth-9, PEG-5 Ethylhexanoate, Water 1.O Neo-PCL. Water Soluble N Tetrahydroxypropyl Ethylendiamine — 1.4 Neutrol TE Cetearyl Erhylhexanoate O.2 PCL Liquid 100 PEG-15 Cocopolyamine 3.0 Polyguart H-81 Propane Butane 6O.O Water (Aqua), Glycerin, PEG-40 Hydrogenated O.S Castor Oil, Rosa Damascena Flower Oil Cyclopentasiloxane, Cyclohexasiloxane O.1 Rose CL forte Sodium Chloride O.8 OS 2.0 Sodium Hydroxide O.S 0.1 — O.S PEG-40 Hydrogenated Castor Oil, Trideceth-9, 2.0 (0.8 Propylene Glycol, Water (Aqua) Pentylene Glycol, Butylene Glycol, Hydroxy- 1.O phenyl Propamidobenzoic Acid SymCalmin 2 Hexanediol, Caprylylglycol — 1.0 O.S Symdiol 68 Echinacea Purpurea Extract O.OS Symfinity 1298 Pentylene Glycol, Isochrysis Galbana Extract 0.5 — — 3.0 Sym Hair Force 1631 Trideceth-9, PEG-5 Isononaoate, Water (Aqua) 1.O SymMollient WIS Phenoxyethanol, Decylene Glycol, 1.2 Hexanediol 0.8 O.S — 1.0 1.O Symocide PS Bisabolol, Hydroxymethoxyphenyl Decanone O.OS - Sym Relief S Hexyldecanol, Bisabolol, Cetylhydroxyproline O.S Palmitamide, Stearic Acid, Brassica Campestris (Rapeseed) Sterols Sym Repair 100 Fragrance O.3 O.3 0.3 O.2 O.OS 0.2 O.S. O.1 O.2 Pentylene Glcol, 4-t-Butylcyclohexanol 1.O SymSitive 1609 Water (Aqua), Pentylene Glycol, Sodium Lauryl — 1.0 Sulfoacetate, Sodium Oleoyl Sarcosinate, Sodium Chloride, Disodium Sulfoacetate, Sodium Oleate, Sodium Sulfate SymSol PF-3 Caprylyl Glycol, 1.2-Hexanediol, Methylbenzyl O.S Alcohol SymTriol Sodium Laureth Sulfate – 10.0 Texapon N70 Wasser (Aqua) Ad 100

The invention claimed is: ss the content of shogaols Sums up to 1.5 to 6% b.W., 1. A composition comprising a ginger extract comprising the total content of pungent components sums up to about 42 to about 50% b.w.. and (a) 25 to 30% b.w. 6-gingerol; the content of essential oil is less than about 5% b.w. (b) 5 to 10% b.w. 8-gingerol; 2. The composition of claim 1, obtained by subjecting dried (c) 5 to 10% b.w.. 10-gingerol; 60 ginger leaves or roots to solvent extraction or Supercritical (d) 1.5 to 4% b.w. 6-shogaol; extraction with carbon dioxide. O J.W. s 3. A composition according to claim 1, wherein the com (e) 0.3 to 1.3% b.w. 8-shogaol; position is a cosmetic composition. (f) 0.03 to 1% b.w.. 10-shogaol; and 4. A composition according to claim 1, wherein the com 65 position is a pharmaceutical composition. (g) 0.001 to 1% b.w. Zingerone, wherein 5. A composition according to claim 1, in a form for oral the content of gingerols sums up to 35 to 50% b.w. administration. US 9,125,936 B2 53 54 6. A composition according to claim 1, wherein the com (a) ginger roots are frozen at about -10 to about -25°C.; position is a medicament for protecting stem cells. 7. A composition according to claim 1, wherein the com (b) the frozen roots are shredded, cut and dried at about 20 position is a medicament for inhibiting the cyclooxygenase-2 to about 50° C. for about 10 to about 30 hours; (COX-2) activity and prostaglandin E2 release. (c) the dried roots are subjected to supercritical extraction 8. A composition according to claim 1, wherein the ginger with carbon dioxide at about 25 to about 90° C. and extract is a protection agent for stem cells. about 220 to about 370 bar for up to 10 hours; and 9. A composition according to claim 1, wherein the ginger (d) the extraction product obtained after about 3 hours is extract is an anti-oxidant agent. collected while the forerun taken from the first three 10. A composition according to claim 1, wherein the ginger hours is dismissed. extract is an anti-inflammation agent. 14. A therapeutical method for preserving stem cells by 11. A composition according to claim 1, wherein the ginger oral administration of a working amount of the ginger extract extract is an anti-aging agent for skin and hair. of claim 1 to an individual. 12. The composition of claim 2, wherein the total content of pungent components Sums up to about 42 to about 50% 15. A non-therapeutical method for preserving stem cells b.w.. and the content of essential oil is less than about 5% b.w. 15 by topical administration of a working amount of the extract 13. A process for obtaining the ginger extract of claim 1, of claim 1 to skin or hair of an individual. wherein k k k k k