WO2017102589A1 - Composition comprising niacinamide and alpha-arbutin for skin lightening - Google Patents
Composition comprising niacinamide and alpha-arbutin for skin lightening Download PDFInfo
- Publication number
- WO2017102589A1 WO2017102589A1 PCT/EP2016/080465 EP2016080465W WO2017102589A1 WO 2017102589 A1 WO2017102589 A1 WO 2017102589A1 EP 2016080465 W EP2016080465 W EP 2016080465W WO 2017102589 A1 WO2017102589 A1 WO 2017102589A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- alpha
- arbutin
- skin
- niacinamide
- range
- Prior art date
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- HAAYBYDROVFKPU-UHFFFAOYSA-N silver;azane;nitrate Chemical compound N.N.[Ag+].[O-][N+]([O-])=O HAAYBYDROVFKPU-UHFFFAOYSA-N 0.000 description 1
- 230000008591 skin barrier function Effects 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229940045898 sodium stearoyl glutamate Drugs 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- KDHFCTLPQJQDQI-BDQAORGHSA-M sodium;(4s)-4-amino-5-octadecanoyloxy-5-oxopentanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)OC(=O)[C@@H](N)CCC([O-])=O KDHFCTLPQJQDQI-BDQAORGHSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940057429 sorbitan isostearate Drugs 0.000 description 1
- 229950004959 sorbitan oleate Drugs 0.000 description 1
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229940010735 steareth-12 Drugs 0.000 description 1
- 229940098760 steareth-2 Drugs 0.000 description 1
- 229940100459 steareth-20 Drugs 0.000 description 1
- 229940073743 steareth-20 methacrylate Drugs 0.000 description 1
- 229940100458 steareth-21 Drugs 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 230000000475 sunscreen effect Effects 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
- 238000004383 yellowing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/60—Sugars; Derivatives thereof
- A61K8/602—Glycosides, e.g. rutin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/673—Vitamin B group
- A61K8/675—Vitamin B3 or vitamin B3 active, e.g. nicotinamide, nicotinic acid, nicotinyl aldehyde
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
Definitions
- the present invention relates to a novel composition comprising niacinamide and alpha- arbutin as well as to the use of such compositions for skin lightening. More particularly, the present invention relates to use of niacinamide to synergistically enhance the skin lightening activity of alpha-arbutin.
- Synthetic skin lighteners such as hydroquinone or kojic acid are known as very effective skin-lightening ingredients, which, however, may cause skin irritation or acute dermatitis are thus not very much appreciated by the cosmetic industry anymore.
- Alpha-arbutin (4-hydroxyphenyl alpha-glucopyranoside; CAS: 84380-01 -8) is currently used as safer alternative to hydroquinone and kojic acid but needs to be applied in concentration up to 2 wt.-% to exhibit a perceivable whitening efficacy. This dosage regime results however in a significant market limitation as alpha-arbutin is therefore not very attractive when it comes to cost-in-use.
- Niacinamide (CAS 98-92-0) is said to be an amazing ingredient, which reduces fine lines and wrinkles, hyperpigmented spots, red blotchiness, skin sallowness (yellowing) and inflammation and increases elasticity, hydration and barrier function of the stratum corneum. Its skin-lightening efficacy is however very limited, and if at all, only perceivable at quite high concentration levels.
- skin lightening refers to smoothening of skin color irregularities, lightening/brightening of skin, prevention of tanning and/or prevention of re- pigmentation, protection against sun or UV-induced skin darkening as well as reducing the melanin level of human skin.
- the first object of the present invention relates to a topical composition comprising niacinamide and alpha-arbutin, characterized in that the amount of alpha-arbutin is selected in the range of 0.05 to 0.5 wt.-% based on the total weight of the topical composition and the weight-ratio of niacinamide to alpha-arbutin is selected in the range of 50 to 5.
- the amount of alpha-arbutin is selected in the range of 0.075 to 0.3 wt.-%, more preferably in the range of 0.1 to 0.25 wt.-% based on the total weight of the topical composition and the ratio of niacinamide to alpha-arbutin is selected in the range of 30 to 5, more preferably in the range of 25 to 5, most preferably in the range of 20 to 5, such as advantageously in the range of 15 to 6, and more advantageously in the range of 12 to 8.
- the amount of alpha-arbutin is selected in the range of 0.1 to 0.3 wt.-% and the weight ratio of niacinamide to alpha-arbutin is se- lected in the range of 15 to 6.
- the amount of alpha-arbutin is selected in the range of 0.15 to 0.25 wt.-% and the weight ratio of niacinamide to alpha-arbutin is selected in the range of 12 to 8.
- keratinous as used herein is understood to mean external application to keratinous substances, which are in particular the skin, scalp, eyelashes, eyebrows, nails, mucous membranes and hair.
- the topical composition is a cosmetic composition or a pharmaceutical composition. Most preferably, it is a cosmetic composition.
- compositions according to the invention are intended for topical application, they comprise a physiologically acceptable medium, that is to say a medium compatible with keratinous substances, such as the skin, mucous membranes, and keratinous fibers.
- physiologically acceptable medium is a cosmetically acceptable carrier.
- cosmetic carrier refers to all carriers and/or excipients and/or diluents conventionally used in cosmetic compositions.
- Preferred cosmetic compositions according to the invention are skin care preparations.
- Examples of skin care preparations are, in particular, skin-lightening preparations, prepa- rations for the treatment of photo-ageing, light protective preparations (sunscreens), anti- ageing preparations, treatment creams, as well as BB and CC Creams.
- topical compositions according to the invention are skin care preparations, such as milks, lotions, hydrodispersions, foundations, creams, creamgels, serums, toners, masks or gels.
- compositions according to the present invention may be in the form of a suspension or dispersion in solvents or fatty substances, or alternatively in the form of an emulsion or micro emulsion (in particular of oil-in-water (O/W) or water-in-oil (W/0)type, silicone-in-water (Si/W) or water-in-silicone (W/Si) type, PIT-emulsion, multiple emulsion (e.g.
- the topical compositions according to the present invention are advantageously in the form of an oil-in-water (O/W) emulsion comprising an oily phase dispersed in an aqueous phase in the presence of an O/W emulsifier.
- O/W oil-in-water
- the preparation of such O/W emulsions is well known to a person skilled in the art.
- the topical composition according to the invention is an O/W emulsion, then it contains advantageously at least one O/W- or Si/W-emulsifier selected from the list of PEG-30 Dipolyhydroxystearate, PEG-4 Dilaurate, PEG-8 Dioleate, PEG-40 Sorbitan Peroleate, PEG-7 Glyceryl Cocoate, PEG-20 Almond Glycerides, PEG-25 Hydrogenated Castor Oil, Glyceryl Stearate (and) PEG-100 Stearate , PEG-7 Olivate, PEG-8 Oleate, PEG-8 Laurate, PEG-60 Almond Glycerides, PEG-20 Methyl Glucose Sesquistearate, PEG-40 Stearate, PEG-100 Stearate, PEG-80 Sorbitan Laurate, Steareth-2, Steareth-12, Oleth-2, Ceteth-2, Laureth-4, Oleth-10, Oleth-10/Polyoxyl 10 Oleyl Ether
- emulsifiers are phosphate esters and the salts thereof such as cetyl phosphate (Amphi- sol ® A), diethanolamine cetyl phosphate (Amphisol ® DEA), potassium cetyl phosphate (Amphisol ® K), sodiumcetearylsulfat, sodium glyceryl oleate phosphate, hydrogenated vegetable glycerides phosphate and mixtures thereof.
- emulsifiers are sorbitan oleate, sorbitan sesquioleate, sorbitan isostearate, sorbitan trioleate, Cetearyl Glucoside, Lauryl Glucoside, Decyl Glucoside, Sodium Stearoyl Glutamate, Sucrose Polystearate and Hydrated Polyisobuten.
- one or more synthetic polymers may be used as an emulsifier.
- PVP eicosene copolymer acrylates/C 10-30 alkyl acrylate crosspolymer, acrylates/steareth-20 methacrylate copolymer, PEG- 22/dodecyl glycol copolymer, PEG-45/dodecyl glycol copolymer, and mixtures thereof.
- a particular suitable O/W emulsifier to be used in the topical compositions according to the invention is potassium cetyl phosphate e.g. commercially available as Amphisol ® K at DSM Nutritional Products Ltd Kaiseraugst.
- the at least one O/W, respectively Si/W emulsifier is preferably used in an amount of 0.5 to 10 wt. %, in particular in the range of 0.5 to 6 wt.-% such as more in particular in the range of 0.5 to 5 wt.-% such as most in particular in the range of 1 to 4 wt.-%, based on the total weight of the composition.
- O/W emulsifiers are polyethyleneglycol (PEG) esters or diesters such as e.g. [I NCI Names] PEG-100 Stearate, PEG-30 Dipolyhydroxystearate, PEG-4 Dilaurate, PEG-8 Dioleate, PEG-40 Sorbitan Peroleate, PEG-7 Glyceryl Cocoate, PEG-20 Almond Glycerides, PEG-25 Hydrogenated Castor Oil, PEG-7 Olivate, PEG-8 Oleate, PEG-8 Laurate, PEG-60 Almond Glycerides, PEG-20 Methyl Glucose Sesquistearate, PEG-40 Stearate, PEG-100 Stearate, PEG-80 Sorbitan Laurate.
- PEG polyethyleneglycol
- diesters such as e.g. [I NCI Names] PEG-100 Stearate, PEG-30 Dipolyhydroxystearate, PEG-4 Dilaurate, PEG-8 Diole
- PEG-100 Stearate sold under the tradename ArlacelTM 165 (INCI Glyceryl Stearate (and) PEG-100 Stearate) by Croda.
- O/W emulsifiers are non-ionic self-emulsifying system derived from olive oil e.g. known as (INCI Name) cetearyl olivate and sorbitan olivate (Chemical Composition: sorbitan ester and cetearyl ester of olive oil fatty acids) sold under the tradename OLIVEM 1000.
- the invention relates to topical compositions with all the definitions and preferences given herein in the form of O/W emulsions comprising an oily phase dispersed in an aqueous phase in the presence of an O/W emulsifier wherein the O/W emulsifier is potassium cetyl phosphate.
- the cosmetic compositions according to the present invention can be prepared by conventional methods in the art such as e.g. by admixing niacinamide and alpha arbutin in the respective amounts and ratios according to the present invention with the cosmetically acceptable carrier.
- the cosmetic compositions of the invention may comprise further conventional cosmetic adjuvants and additives, such as preservatives/antioxidants (e.g. sodium metabisulfite), fatty substances/oils, water, organic solvents, silicones, thickeners, softeners, emulsifiers, antifoaming agents, aesthetic components such as fragrances, sur- factants, fillers, anionic, cationic, nonionic or amphoteric polymers or mixtures thereof, propellants, acidifying or basifying agents, dyes, colorings/colorants, abrasives, absorbents, chelating agents and/ or sequestering agents, essential oils, skin sensates, astringents, pigments or any other ingredients usually formulated into such compositions.
- preservatives/antioxidants e.g. sodium metabisulfite
- fatty substances/oils water, organic solvents, silicones, thickeners, softeners, emulsifiers, antifoaming agents
- aesthetic components such as fragrances
- the cosmetic compositions according to the invention may also comprise further cosmetically active ingredients conventionally used in cosmetic compositions.
- exemplary active ingredients encompass UV-filters, agents for the treatment of hyperpigmentation; agents for the prevention or reduction of inflammation; firming, moisturizing, soothing, and/ or energizing agents as well as agents to im- prove elasticity and skin barrier.
- cosmetic excipients examples include diluents, adjuvants, additives as well as active ingredients commonly used in the skin care industry which are suitable for use in the cosmetic compositions of the present invention are for example described in the International Cos- metic Ingredient Dictionary & Handbook by Personal Care Product Council
- the necessary amounts of the active ingredients as well as the cosmetic excipients, dilu- ents, adjuvants, additives etc. can, based on the desired product form and application, easily be determined by the skilled person.
- the additional ingredients can either be added to the oily phase, the aqueous phase or separately as deemed appropriate.
- cosmetically active ingredients useful herein can in some instances provide more than one benefit or operate via more than one mode of action.
- one skilled in this art will take care to select the above mentioned optional additional compound or compounds and/or their amounts such that the advantageous properties intrinsically associated with the combination in accordance with the invention are not, or not substantially, detrimentally affected by the envisaged addition or additions.
- the topical compositions according to the invention in general have a pH in the range of 3 to 10, preferably a pH in the range of 4 to 8 and most preferably a pH in the range of 4 to 7.5.
- the pH can easily be adjusted as desired with suitable acids such as e.g. citric acid or bases such as sodium hydroxide (e.g. as aqueous solution), Triethanolamine (TEA Care), Tromethamine (Trizma Base) and Aminomethyl Propanol (AMP-Ultra PC 2000) according to standard methods in the art.
- the amount of the topical composition to be applied to the skin is not critical and can easily be adjusted by a person skilled in the art.
- the amount is selected in the range of 0.1 to 3 mg/ cm2 skin, such as preferably in the range of 0.1 to 2 mg/ cm2 skin and most preferably in the range of 0.5 to 2 mg / cm2 skin.
- a further object of the present invention is the (cosmetic) use of niacinamide and alpha- arbutin for skin lightening such as in particular for smoothening of skin color irregularities, prevention of tanning and/or prevention of re-pigmentation, protection against sun or UV- induced skin darkening as well as reducing the melanin level of human skin, characterized that the weight-ratio of niacinamide to alpha-arbutin is selected in the range of 50 to 5, preferably in the range of 30 to 5, more preferably in the range of 25 to 5, most preferably in the range of 20 to 5, such as advantageously in the range of 15 to 6, and more ad- vantageously in the range of 12 to 8.
- the invention also relates to niacinamide and alpha-arbutin for use in a topical pharmaceutical composition for the treatment and prevention of skin pigmentation disorders with all the definitions and preferences as given above for the top- ical compositions.
- Another object of the present invention is the use of niacinamide for enhancing the skin lightening activity of alpha-arbutin, whereby preferably the weight-ratio of niacinamide to alpha-arbutin is selected in the range of 50 to 5, preferably in the range of 30 to 5, more preferably in the range of 25 to 5, most preferably in the range of 20 to 5, such as advantageously in the range of 15 to 6, and more advantageously in the range of 12 to 8.
- the present invention also relates to a (cosmetic) method of lightening human skin such as in particular smoothening of skin color irregularities, prevention of tanning and/or prevention of re-pigmentation, protection against sun or UV-induced skin darkening as well as reducing the melanin level of human skin, which method comprises topically adminis- tering an effective amount of a composition according to the present invention to the appropriate skin area of a person in need of such treatment and optionally appreciating the effect.
- a (cosmetic) method of lightening human skin such as in particular smoothening of skin color irregularities, prevention of tanning and/or prevention of re-pigmentation, protection against sun or UV-induced skin darkening as well as reducing the melanin level of human skin, which method comprises topically adminis- tering an effective amount of a composition according to the present invention to the appropriate skin area of a person in need of such treatment and optionally appreciating the effect.
- composition according to the present invention relates to a method of treating or preventing pigmentation disorders which comprises topically administering an effective amount of a composition according to the present invention to the appropriate skin area of a person in need of such treatment, and optionally appreciating the effect.
- the term 'an effective amount' refers to an amount necessary to obtain a physiological ef- feet.
- the physiological effect may be achieved by one application dose or by repeated applications.
- the dosage administered may, of course, vary depending upon known factors, such as the physiological characteristics of the particular composition and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; and the effect desired and can be adjusted by a person skilled in the art.
- the amount of the topical composition to be applied to the skin is selected in the range of 0.1 to 3 mg/ cm2 skin, such as preferably in the range of 0.1 to 2 mg/ cm2 skin and most preferably in the range of 0.5 to 2 mg / cm2 skin.
- the present invention also relates to a method as described above, wherein, from about 0.2 ⁇ g to about 200 ⁇ g of niacinamide and alpha-arbutin, (calculated as the sum of the amount of both compounds), are applied per square centimeter of skin per day.
- Skin equivalents were received on agarose plaques under sterile conditions. After arrival they were transferred to 6well plates and fed with 2ml of maintenance medium overnight at 37°C to equilibrate according to the manufacturer's instructions. To start the testing, a volume of 25 ⁇ _ has been applied on top at non-toxic concentration. Dosing has been performed every second day, together with a change of medium. Skin models were kept in wells of a 6well culture plate and cultivated for a time period of 9 days in an incubator at 37°C and 5% C0 2 atmosphere.
- MTT stock solution (5mg/ml_) was diluted to 1 mg/mL in PBS. 300 ⁇ _ of the working solution was added to each well of a new 24-well plate. The tissues were then transferred into the wells and the plate was incubated for 3hrs at 37°C and 5% CO2 humidified atmosphere. After that, 800 ⁇ _ of 2-Propanol was filled into each well of a new 24-well plate and the tissues were transferred from the MTT-plate to the new plate. To cover the tissues completely with 2-Propanol, 700 ⁇ _ of 2-Propanol were added into the inserts. The plate was sealed with parafilm and incubated for 2 hrs. at room temperature with gentle agitation on a shaker.
- niacinamide itself does not result in skin lightening whereas the combination of niacinamide and alpha arbutin in a ratio of 9:1 results in a significant improvement, comparable to the effect of kojic acid.
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- Epidemiology (AREA)
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Abstract
Description
Claims
Priority Applications (2)
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KR1020187019772A KR20180094964A (en) | 2015-12-14 | 2016-12-09 | Compositions comprising niacinamide and alpha-arbutin for skin lightening |
CN201680072501.8A CN108366952A (en) | 2015-12-14 | 2016-12-09 | The composition for including niacinamide and alpha-arbutin for skin lightening |
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EP15199895.2 | 2015-12-14 | ||
EP15199895 | 2015-12-14 |
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PCT/EP2016/080465 WO2017102589A1 (en) | 2015-12-14 | 2016-12-09 | Composition comprising niacinamide and alpha-arbutin for skin lightening |
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KR (1) | KR20180094964A (en) |
CN (1) | CN108366952A (en) |
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CN108498413A (en) * | 2018-07-05 | 2018-09-07 | 上海新高姿化妆品有限公司 | A kind of cosmetic composition containing whitening compound |
CN108542831A (en) * | 2018-07-05 | 2018-09-18 | 上海新高姿化妆品有限公司 | A kind of whitening and skin-protecting water and preparation method thereof with collaboration whitening effect |
CN108619033A (en) * | 2018-07-05 | 2018-10-09 | 上海新高姿化妆品有限公司 | Whitening and skin-protecting essence and preparation method thereof with collaboration whitening effect |
CN108653092A (en) * | 2018-07-05 | 2018-10-16 | 上海新高姿化妆品有限公司 | A kind of cosmetic composition with collaboration whitening effect |
CN108653093A (en) * | 2018-07-05 | 2018-10-16 | 上海新高姿化妆品有限公司 | A kind of cosmetic composition with whitening skin lightening |
CN115252899A (en) * | 2022-09-13 | 2022-11-01 | 济南之羽医疗科技有限公司 | Freeze-dried powder containing recombinant human collagen and preparation method thereof |
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KR102165565B1 (en) * | 2019-07-22 | 2020-10-14 | 주식회사 오퍼스아시아 | Cosmetic composition with excellent blemish and blemishes |
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- 2016-12-09 WO PCT/EP2016/080465 patent/WO2017102589A1/en active Application Filing
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- 2016-12-09 CN CN201680072501.8A patent/CN108366952A/en active Pending
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