Medicament comprising ginger root CO2 extract

Abstract

The present invention belongs to the fields of pharmaceuticals and cosmetics, and concerns on the one hand a medicament for the inhibition of and refers also on the cosmetic, non-therapeutic use for the treatment of hyperpigmentation, particularly induced by sun light radiation, preferably induced by visible light radiation.

Claims

1. A method for treating hyperpigmentation in a human in need thereof consisting essentially of administering to a human in need thereof, a therapeutically effective amount of a mixture of a) at least a ginger root CO2 extract, b) at least one skin lightening agent selected from the group consisting of sclareolide and phenylethyl resorcinol and mixtures thereof, c) at least one carrier selected from the group consisting of glycerol, propylene glycol, butylene glycol, dipropylene glycol, pentylene glycol, 1,2-hexane diol, caprylyl glycol, decylene glycol and mixtures thereof, and d) a compound selected from the group consisting of homomenthyl salicylate, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate, 2-phenylbenzimidazole sulfonic acid, 2-ethylhexyl salicylate, and mixtures thereof, to effectively treat the hyperpigmentation in the human in need thereof.

2. The method claim 1, wherein the ginger root CO2 extract consists essentially of an extract I) or II) that consists essentially of: extract I): (a) 25 to 30% b.w. [6]-gingerol; (b) 5 to 10% b.w. [8]-gingerol; (c) 5 to 10% b.w. [10]-gingerol; (d) 1.5 to 4% b.w. [6]-shogaol; (e) 0.3 to 1.3% b.w. [8]-shogaol; (f) 0.03 to 1% b.w. [10]-shogaol; (g) 0.01 to 1% b.w. zingerone, wherein the amount of gingerols sums up to 35 to 50% b.w. and the amount of shogaols sums up to 1.5 t 6% b.w.; or extract II): (a) 15 to 25% b.w. [6]-gingerol; (b) 3 to 5% b.w. [8]-gingerol; (c) 3 to 8% b.w. [10]-gingerol; (d) 0.5 to 3% b.w. [6]-shogaol; (e) 0.03 to 1% b.w. [8]-shogaol; (f) 0.03 to 1% b.w. [10]-shogaol; (g) 0.01 to 1% b.w. zingerone, wherein the amount of gingerols sums up to 24 to 35% b.w. and the amount of shogaols sums up to 0.5 to 5% b.w.

3. The method of claim 1, consisting essentially of applying the mixture having (a) from 0.001 wt. % to 0.2 wt. % of said ginger root CO2 extract, (b) from 0.01 wt. % to 10 wt. % of said skin lightening agent, and (c) from 1 wt. % to 10 wt. % of said carrier, in a weight ratio of (a):(b) of 1:1 to 1:5.

4. The method of claim 1, wherein the hyperpigmentation is induced by visible light with a wavelength in the range from 400 nm to 700 nm.

Description

EXAMPLES

Example 1

(1) Human epidermal melanoma cells A375 were cultured in 6-well plates. The cells were exposed to visible light (480 J/cm2) with Hydrosun 750 equipped with KG1 filter. 48 h prior to and past to the irradiation the cells were treated with test compounds in non-cytotoxic concentrations. Melanocytes were lysed in a solution of NaOH. Melanin was quantified by measurement of absorbance at 405 nm and calculation based on a melanin standard curve.

(2) TABLE-US-00001 TABLE 1 Basal melanin formation in vitro melanin [μg] Significance untreated 0.7914 ± 0.07 0.0001% ginger root CO2 extract 0.8024 ± 0.13 no significance 0.000316% ginger root CO2 extract 0.6040 ± 0.04 no significance 0.001% ginger root CO2 extract 0.6509 ± 0.08 no significance

(3) TABLE-US-00002 TABLE 2 Visible light induced hyperpigmentation in vitro Inhibition vs melanin visible light [μg] induced [%] Significance untreated 0.4581 visible light 0.9731 ### (vs irradiated untreated) 0.0001% ginger 0.8233 29% root CO2 extract 0.000316% ginger 0.5590 80% ** (vs visible root CO2 extract light irradiated) 0.001% ginger 0.4425 103% *** (vs visible root CO2 extract light irradiated) Significance: ## p < 0.01 versus untreated; ** P < 0.01, *** p < 0.001 versus visible light irradiated

(4) It has been surprisingly shown that ginger root CO2 extract inhibits significantly the visible light induced hyperpigmentation whereas there is no effect on basal melanin formation.

Example 2

(5) The below formulations were applied on ex vivo human skin explants from abdominal surgery of a donor with phototype IV (Fitzpatrick scale). 48 h after the formulations were removed with a cotton pad. Skin explants were exposed to visible light (480 J/cm2) with Hydrosun 750 equipped with KG1 filter. Formulations were reapplied afterwards. 48 h later skin sections were prepared and melanin was stained by Fontana-Masson stain. Quantification of melanin was done by image analysis.

(6) TABLE-US-00003 TABLE 3 Formulations applied to ex vivo human skin (all amounts w/w %) Phase Ingredients INCI A B C A. H2O, demin. Water (Aqua) 84.75 84.55 84.70 Hydrolite-5 Pentyleneglycol 1.00 1.00 1.00 B. PCL liquid Cetearyl Octanoate 3.00 3.00 3.00 100 Lanette O Cetearyl Alcohol 2.00 2.00 2.00 Mineral Oil Mineral Oil 3.00 3.00 3.00 5° E Eutanol G PN Octyldodecanol 4.00 4.00 4.00 Abil 350 Dimethicone 0.50 0.50 0.50 C. Pemulen TR1 Acrylates/C10-30 0.20 0.20 0.20 Alkyl Acrylate Crosspolymer Ultrez-21 Acrylates/C10-30 0.05 0.05 0.05 Alkyl Acrylate Crosspolymer D. Sodium Sodium Hydroxide 0.50 0.50 0.50 hydroxid Sol. 10% E. Ginger Zingiber Officinale — 0.20 0.05 root CO2 (Ginger) Root extract Extract Hydrolite-5 Pentyleneglycol 1.00 1.00 1.00 Sum 100.0 100.0 100.0

(7) TABLE-US-00004 TABLE 4 Melanin formation after visible light irradiation on ex vivo human skin Inhibition vs % of melanin Placebo [%] untreated 33.22 ± 3.7 Placebo 61.68 ± 1.7 0.05% Ginger root CO2 extract 49.21 ± 2.2 43.8% 0.2% Ginger root CO2 extract 55.48 ± 3.7 21.8%

(8) The following examples show formulations for various sun protection products that contain the preparations according to the invention. All amounts are to be understood as indicating wt %.

(9) Cosmetic Sun Protection Agent

(10) TABLE-US-00005 Components Amount Ethylhexyl cinnamic acid 7.50 Benzophenone-3 2.00 Polyglyceryl dimer soyate 0.80 Sorbitan stearate 1.00 Tocopheryl acetate 0.50 Glyceryl stearate. PEG-100 Stearate 3.00 PEG-40. Hydrogenated castor oil 1.00 Titanium dioxide. Aluminum oxide hydrate. 3.00 Dimethicone/methicone copolymer Butyrospermum parkii (shea butter) 1.00 C12-15 alkyl benzoate 6.50 Butylene glycol 5.00 Xanthan gum 0.30 Disodium EDTA 0.10 Allantoin 0.10 Polyacrylamide. C13-14 isoparaffin. Laureth-7 1.00 Pentylene glycol 5.00 4-t-Butyl cyclohexanol 1.00 Ginger root CO2 extract 0.20 Benzylidene Dimethoxydimethylindanone 0.30 Preservatives (methyl, butyl, ethyl, 0.30 propylparaben, phenoxyethanol) Aqua dem. Ad 100

(11) Sun Protection Spray

(12) TABLE-US-00006 Components INCI Amount Water, demineralized Water (aqua) 69.00 Glycerol Glycerol 4.00 1,3-butylene glycol Butylene glycol 5.00 D-Panthenol Panthenol 0.50 Lara care A-200 Galactoarabinan 0.25 Baysilone oil M 10 Dimethicone 1.00 Edeta BD Disodium EDTA 0.10 Copherol 1250 Tocopheryl acetate 0.50 Cetiol OE Dicaprylyl ether 3.00 Neo Heliopan ® HMS Homosalate 5.00 Neo Heliopan ® AV Ethylhexyl methoxycinnamate 6.00 Neo Heliopan ® 357 Butyl methoxydibenzoyl methane 1.00 Corapan TQ Diethylhexylnaphthalate 2.00 Alpha Bisabolol Bisabolol 0.10 Pemulen TR-2 Acrylates/C10-30 alkyl acrylate 0.25 crosspolymer NaOH 10% Sodium hydroxide 0.60 Perfume oil Fragrance 0.20 Phenoxyethanol Phenoxyethanol 0.40 SymSave ® H Hydroxyacetophenone 0.50 Solbrol M Methylparaben 0.10 Solbrol P Propylparaben 0.10 Ginger root CO2 extract Zingiber Officinale (Ginger) 0.10 Root Extract

(13) Sun Protection Spray O/W SPF 15-20

(14) TABLE-US-00007 Components INCI Amount Dracorin ® GOC Glyceryl oleate citrate. 2.00 Caprylic/capric triglyceride Corapan ® TQ. Diethylhexyl 2,6-naphthalate 3.00 Neo Heliopan ® HMS Homosalate 7.00 Neo Heliopan ® OS Ethylhexyl salicylate 5.00 Neo Heliopan ® 357 Butyl methoxydibenzoyl methane 3.00 Isoadipate Diisopropyl adipate 6.00 Baysilone ® Oil M10 Dimethicone 1.00 Edeta ® BD Disodium EDTA 0.10 Vitamin E acetate Tocopheryl acetate 0.50 Dragosantol ® 100 Bisabolol 0.10 Pemulen ® TR-2 Acrylates/C10-30 alkyl 0.25 acrylate crosspolymer Glycerol 99.5 P Glycerol 4.00 Butylene glycol Butylene glycol 5.00 Neo Heliopan ® hydro Phenylbenzimidazole 8.00 (103089). Used as 25% sulfonic acid aq. solution neutralized with Biotive ® L-Arginine Biotive ® L-Arginine Arginine 0.55 SymWhite 377 Phenylethyl Resorcinol 0.1 Perfume oil Fragrance 0.40 Sobrol M Methylparaben 0.30 Ginger root CO2 extract Zingiber Officinale 0.20 (Ginger) Root Extract Water Water (Aqua) Ad 100

(15) Sun Protection Soft Cream W/O SPF 40

(16) TABLE-US-00008 Components INCI Amount Dehymuls PGPH Polyglyceryl-2 5.00 dipolyhydroxystearate Copherol 1250 Tocopheryl acetate 0.50 Permulgin 3220 Ozocerite 0.50 Zinc stearate Zinc stearate 0.50 Tegosoft TN C12-15 alkyl benzoate 10.00 Neo Heliopan ® E1000 Isoamyl-p-methoxycinnamate 2.00 Neo Heliopan ® 303 Octocrylene 5.00 Neo Heliopan ® MBC 4-methylbenzylidene camphor 3.00 Zinc oxide, neutral Zinc oxide 5.00 EDETA BD Disodium EDTA 0.10 Glycerol Glycerol 4.00 Magnesium sulfate Magnesium sulfate 0.50 Perfume oil P1, P2, Perfume 0.30 P3, or P4 Symdiol ® 68 1,2-hexane diol. Caprylyl glycol 0.30 Ginger root CO2 extract Zingiber Officinale 0.10 (Ginger) Root Extract Water, distilled Water (aqua) Add 100

(17) Sun Protection Lotion W/O

(18) TABLE-US-00009 Components INCI Amount Dehymuls PGPH Polyglyceryl-2 3.00 dipolyhydroxystearate Beeswax 8100 Beeswax 1.00 Monomuls 90-0-18 Glyceryl oleate 1.00 Zinc stearate Zinc stearate 1.00 Cetiol SN Cetearyl isononanoate 5.00 Cetiol OE Dicaprylyl ether 5.00 Tegosoft TN C12-15 alkyl benzoate 4.00 Vitamin E Tocopherol 0.50 Neo Heliopan ® OS Ethylhexyl salicylate 5.00 Neo Heliopan ® AV Ethylhexyl methoxycinnamate 7.50 Uvinul ® T150 Ethylhexyl triazone 1.50 Trilon BD Disodium EDTA 0.10 Glycerol Glycerol 5.00 Neo Heliopan ® Disodium phenyl 15.00 AP 10% solution. dibenzimidazole tetra- Neutralized with NaOH sulfonate Perfume oil Perfume 0.25 Alpha bisabolol Bisabolol 0.10 SymOcide ® PT Phenoxyethanol. Tropolone 0.25 Ginger root CO2 Zingiber Officinale 0.05 extract (Ginger) Root Extract Water, distilled Water (Aqua) ad 100

(19) After-Sun Gel

(20) TABLE-US-00010 Components INCI Amount SymSol ® PF-3 Water (aqua). Pentylene glycol. 3.00 Sodium lauryl sulfoacetate. Sodium oleoyl sarcosinate. Sodium chloride. Disodium sulfoacetate. Sodium oleate. Sodium sulfate Glycerol 99.5 P. Glycerol 5.00 SymUrban ® 1031 Benzylidene dimethoxy 0.10 dimethylene danone Pemulen ® TR-2 Acrylates/C10-30 alkyl 1.00 acrylate crosspolymer D-Panthenol 75 W Panthenol 0.50 SymFinity ® 1298 Echinacea purpurea extract 0.10 Extrapone ® Pearl Water (aqua). Glycerol. 1.00 GW Hydrolyzed pearl. Xanthan gum Sodium hydroxide Sodium hydroxide 2.50 10% solution Ethanol 96% Alcohol denat. 15.00 Perfume oil Perfume 0.20 SymOcide ® PS Phenoxyethanol. 1,2-Hexanediol. 0.50 Decylene glycol Ginger root CO2 Zingiber Officinale 0.10 extract (Ginger) Root Extract Water Water (aqua) Ad 100

(21) Night Recovery Cream

(22) TABLE-US-00011 Component INCI Amount Aqua/Water Aqua ad 100 SymSave ® H Hydroxyacetophenone 0.5 SymDiol ® 68 1,2-Hexanediol 0.5 Caprylyl Glycol SymVital ® AR 3040 Zingiber Officinale 0.2 (Ginger) Root Extract Edeta ® BD Disodium Edta 0.1 Emulsiphos ® Potassium Cetyl Phosphate 2.0 Hydrogenated Palm Glycerides Mango Butter Mangifera Indica 2.0 Seed Butter SymMollient ® S Cetearyl Nonanoate 1.0 Dragoxat ® 89 Ethylhexyl Isononanoate 8.5 Lanette ® 16 Cetyl Alcohol 2.0 Lanette ® 0 Cetearyl Alcohol 4.0 SymRepair ® 100 Hexyldecanol 2.0 Bisabolol Cetylhydroxyproline Palmitamide Stearic Acid Brassica Campestris (Rapeseed) Sterols Cetiol ® Ultimate Tridecane 5.0 Undecane Carbopol ® Ultrez Carbomer 0.3 10 Polymer Tapioca Pure Tapioca Starch 2.0 Fragrance Parfum 0.4 Sodium Hydroxide Aqua 0.4 10% solution Sodium Hydroxide Tocopherol alpha DL Tocopherol 0.5

(23) Fresh Watering After Sun Mousse

(24) TABLE-US-00012 Component INCI Amount Aqua/Water Aqua Ad 100 SymSol ® PF-3 Aqua 2.0 Pentylene Glycol Sodium Lauryl Sulfoacetate Sodium Oleoyl Sarcosinate Sodium Chloride Sodium Oleate Aqua Keep 10SH-NFC Sodium Acrylates 2.0 Crosspolymer-2 SymSave ® H Hydroxyacetophenone 0.5 SymDiol ® 68 1,2-Hexanediol 0.5 Caprylyl Glycol Hydrolite ® 5 Pentylene Glycol 3.0 SymVital ® AR 3040 Zingiber Officinale 0.2 (Ginger) Root Extract SymGlucan ® Aqua 1.0 Glycerin 1,2-Hexanediol Caprylyl Glycol Beta-Glucan Lanette ® 0 Cetearyl Alcohol 1.0 SymRepair ® 100 Hexyldecanol 1.0 Bisabolol Cetylhydroxyproline Palmitamide Stearic Acid Brassica Campestris (Rapeseed) Sterols SymSitive ® 1609 Pentylene Glycol 1.0 4-T-Butyl cyclohexanol Frescolat ® Ml Menthyl Lactate 1.0 SymMollient ® S Cetearyl Nonanoate 2.5 Dragoxat ® 89 Ethylhexyl Isononanoate 5.0 Isodragol ® Triisononanoin 3.0 SymUrban ™ Benzylidene 0.3 Dimethoxydimethylindanone Xiameter ® Dimethicone 1.0 Dimethiconol Fragrance Parfum 0.3

(25) Creme Gel for Face

(26) TABLE-US-00013 Component INCI Amount Aqua/Water Aqua ad 100 Symvital ® AR 3040 Zingiber Officinale 0.2 (Ginger) Root Extract Glycerin Glycerin 3.0 Dracorin ® Goc Glyceryl Oleate Citrate 0.3 Caprylic/Capric Triglyceride Jojoba Oil Simmondsia Chinensis Seed Oil 4.0 Avocado Oil Persea Gratissima Oil 4.0 Sweet Almond Oil Prunus Amygdalus Dulcis 4.0 (Sweet Almond) Oil Shea Butter Butyrospermum Parkii Butter 2.0 Symdecanox Ha Caprylic/Capric Triglyceride 1.0 Hydroxymethoxyphenyl Decanone SymWhite ® 377 Phenylethyl Resorcinol 0.2 Cosmedia Sp 1.2 Symocide ® Ps Phenoxyethanol 1.0 Decylene Glycol 1,2-Hexanediol Tapioca Pure Tapioca Starch 1.0

(27) Dreamy Fresh Body Lotion

(28) TABLE-US-00014 Component INCI Amount Emulsiphos ® Potassium Cetyl Phosphate 2.50 Hydrogenated Palm Glycerides Tegin M Glyceryl Stearate 1.20 Pci-Solid ® Stearyl Heptanoate 2.00 Stearyl Caprylate Silcare ® Silicone 41m15 Caprylyl Methicone 4.00 Tocopheryl Acetate Tocopheryl Acetate 0.25 Lanette ® 16 Cetyl Alcohol 0.50 PCL-Liquid ® 100 Cetearyl Ethylhexanoate 5.00 Xiameter ® Pmx-200 Dimethicone 2.00 Silicone Fluid 100 cs Symvital ® AR 3040 Zingiber Officinale 0.10 (Ginger) Root Extract Tego ® Feel Green Cellulose 1.00 Keltrol ® Cg-F Xanthan Gum 0.30 Extrapone ® Aqua 1.00 Watermint P Propylene Glycol Glucose Mentha Aquatica Leaf Extract Glycerin Glycerin 4.00 Extrapone ®Deep Aqua 1.00 Sea Gw Glycerin Thermus Thermophillus Ferment Symwhite Caprylic/Capric Triglycerides, 2.00 Plus ® Pentylene Glycol, Phenylethyl Resorcinol, Bisabolol, Butyl Methoxydibenzoyl Methane Hydrolite ® 5 Pentylene Glycol 4.00 Symsave ® H Hydroxyacetophenone 0.50 Colour 0.81 Dragosine ® Carnosine 0.10 Frescolat ® Ml Menthyl Lactate 0.50 Fragrance Parfum 0,50 Aqua/Water Aqua Ad 100

(29) Eye Lotion

(30) TABLE-US-00015 Component INCI Amount Amount Dracorin ® GOC Glyceryl Oleate Citrate 2.50 2.50 Caprylic/Capric Triglyceride Pci-Liquid ® 100 Cetearyl Ethylhexanoate 2.50 2.50 Isodragol ® Triisononanoin 4.00 4.00 Symmollient ® S Cetearyl Nonanoate 1.50 1.50 Xiameter ® Pmx-200 Dimethicone 1.00 1.00 Silicone Fluid 350 Cs Tocopheryl Acetate Tocopheryl Acetate 0.10 0.10 Carbopol ® Etd 2020 Polymer Acrylates/C10-30 Alkyl Acrylate Crosspolymer 0.15 0.15 Keltrol ® Cg-T Xanthan Gum 0.25 0.25 Symsave ® H Hydroxyacetophenone 0.50 0.50 Symdiol ® 68 1,2-Hexanediol 0.50 0.50 CAPRYLYL GLYCOL Sodium Hydroxide 10% Sol. Aqua, Sodium Hydroxide 0.20 0.20 Simulgel Ns Hydroxyethyl Acrylate/Sodium Acryloyldimethyl 0.60 0.60 Taurate Copolymer SQUALANE POLYSORBATE 60 Hydroviton ® Plus Aqua, Pentylene Glycol, Glycerin, 2.00 2.00 Fructose, Urea, Citric Acid, Sodium Hydroxide, Maltose, Sodium Pea, Sodium Chloride, Sodium Lactate, Trehalose, Allantoin, Sodium Hyaluronate, Glucose Sclareolide Sclareolide 0.10 — Larixol Larixol — 0.10 Ginger root CO2 extract Zingiber Officinale (Ginger) 0.20 0.10 Root Extract Symfinity ® 1298 Echinacea Purpurea Extract 0.10 0.10 Fragrance Parfum 0.30 0.30 Aqua/Water Aqua ad 100 ad 100