WO2017102589A1 - Composition comprising niacinamide and alpha-arbutin for skin lightening - Google Patents

Composition comprising niacinamide and alpha-arbutin for skin lightening Download PDF

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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
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WO
WIPO (PCT)
Prior art keywords
alpha
arbutin
skin
niacinamide
range
Prior art date
Application number
PCT/EP2016/080465
Other languages
French (fr)
Inventor
Remo CAMPICHE
Volker Rosenberger
Kerstin Schenk
Original Assignee
Dsm Ip Assets B.V.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dsm Ip Assets B.V. filed Critical Dsm Ip Assets B.V.
Priority to KR1020187019772A priority Critical patent/KR20180094964A/en
Priority to CN201680072501.8A priority patent/CN108366952A/en
Publication of WO2017102589A1 publication Critical patent/WO2017102589A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60Sugars; Derivatives thereof
    • A61K8/602Glycosides, e.g. rutin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/02Preparations for care of the skin for chemically bleaching or whitening the skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67Vitamins
    • A61K8/673Vitamin B group
    • A61K8/675Vitamin B3 or vitamin B3 active, e.g. nicotinamide, nicotinic acid, nicotinyl aldehyde
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; 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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Abstract

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 the use of niacinamide to synergistically enhance the skin lightening activity of alpha-arbutin.

Description

COMPOSITION COMPRISING NIACINAMIDE AND ALPHA-ARBUTIN FOR
SKIN LIGHTENING
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.
There is a growing demand in the industry, and a growing market need for skin lightening products that are stable, safe, and cost efficient.
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.
Thus, there is still an ongoing need for improved skin lightening products overcoming the drawbacks of the prior art. Surprisingly, it has been found that niacinamide synergistically enhances the skin- lightening efficacy of alpha-arbutin resulting in an efficacy comparable to kojic acid. This finding now allows the formulation of highly efficient, cost-effective skin-lightening compositions as only low amounts of alpha-arbutin have to be employed. The term "skin lightening" as referred to herein 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.
In a preferred embodiment, 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.
Thus, in a particular advantageous embodiment, 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. In an even more advantageous embodiment 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.
The term "topical" 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.
Preferably, the topical composition is a cosmetic composition or a pharmaceutical composition. Most preferably, it is a cosmetic composition.
As the 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. In particular, the physiologically acceptable medium is a cosmetically acceptable carrier.
The term "cosmetically acceptable 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.
In a particular embodiment, the topical compositions according to the invention are skin care preparations, such as milks, lotions, hydrodispersions, foundations, creams, creamgels, serums, toners, masks or gels.
The topical 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. oil-in-water-in oil (0/W/O) or water-in-oil-in-water (W/O/W) type), pickering emulsion, hydrogel, alcoholic gel, lipogel, one- or multiphase solution or vesicular dispersion or other usual forms, which can also be applied by pens, as masks or as sprays. In one embodiment, 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. The preparation of such O/W emulsions is well known to a person skilled in the art. If 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, Ceteth-10, Isosteareth- 20, Ceteareth-20, Oleth-20, Steareth-20, Steareth-21 , Ceteth-20, lsoceteth-20, Laureth- 23, Steareth-100, Glyceryl Stearate Citrate, Glyceryl Stearate SE (self-emulsifying), stea- ric acid, salts of stearic acid, polyglyceryl-3-methylglycosedistearate. Further suitable 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. Further suitable emulsifiers are sorbitan oleate, sorbitan sesquioleate, sorbitan isostearate, sorbitan trioleate, Cetearyl Glucoside, Lauryl Glucoside, Decyl Glucoside, Sodium Stearoyl Glutamate, Sucrose Polystearate and Hydrated Polyisobuten. Furthermore, one or more synthetic polymers may be used as an emulsifier. For example, 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.
Further suitable 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.
Particularly preferred according to the present invention is PEG-100 Stearate sold under the tradename Arlacel™ 165 (INCI Glyceryl Stearate (and) PEG-100 Stearate) by Croda.
Another particular suitable class of 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.
In particular embodiment, 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 (including the carrier) 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. In accordance with the present invention, 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.
Examples of cosmetic excipients, 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
(http://www.personalcarecouncil.org/), accessible by the online INFO BASE
(http://online.personalcarecouncil.org/jsp/Home.jsp), without being limited thereto.
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.
The cosmetically active ingredients useful herein can in some instances provide more than one benefit or operate via more than one mode of action. Of course, 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. Preferably 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.
Yet in another embodiment, 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.
Furthermore, it also 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. Preferably, 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 μg to about 200 μg of niacinamide and alpha-arbutin, (calculated as the sum of the amount of both compounds), are applied per square centimeter of skin per day.
The following examples are provided to further illustrate the compositions and effects of the present invention. These examples are illustrative only and are not intended to limit the scope of the invention in any way.
Examples: Method and Results 3D epidermal model
Cell culture
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 25μΙ_ 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% C02 atmosphere.
Determination of cytotoxicity
In brief, MTT stock solution (5mg/ml_) was diluted to 1 mg/mL in PBS. 300μΙ_ 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, 800μΙ_ 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, 700μΙ_ 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. The tissues were then pierced with a tip and the solutions were homogenized by pipetting up and down. Three times 200μΙ_ of this extraction solutions were then transferred per well into a 96-well plate. 2-Propanol was used as blank. OD was read in an absorbance reader at a wavelength of 570nm. Cytotoxicity was evaluated as single value using only one tissue insert with vehicle control as comparison. Detection of Melanin with Fontana-Masson-Method
3-5μηι thick paraffin sections on silane coated slides were deparaffinised and rehydrated, the slides were incubated with 5% ammoniacal silver nitrate solution in a humidified chamber for 30 min at 56°C. Washed well in several changes of distilled water. Sections were treated with 5% aqueous sodium thiosulfate for 1 minute and washed subsequently in running tap water for 2-3minut.es. Nuclei were stained with hematoxylin for 5 minutes and again washed well in running tap water for 5 minutes. Slides were dehydrated and mounted with cover slips in the presence of Entellan. Melanin content was quantified by measuring melanin area per micrometer of tissue section using cellSense software by Olympus.
Table 1 : Results of Melanin staining and quantification
Compound Melanin content Melanin content
[arbitrary units] [%]
Vehicle 0.23 100% alpha-Arbutin 0.2% 0.23 100% alpha-Arbutin 0.4% 0.05 21 % Niacinamide 1 .8% 0.61 265% alpha-Arbutin 0.2% + Niacinamide 1 .8% 0.03 13%
Kojic acid 0.4% 0.02 9%
Significance (t-test):
Vehicle vs alpha-Arbutin 0.4%, p<0.01
Vehicle vs alpha-Arbutin 0.2% + Niacinamide 1 .8%, p<0.01
alpha-Arbutin 0.4% vs alpha-Arbutin 0.2% + Niacinamide 1 .8%, p<0.05
As can be retrieved from the data presented in table 1 , 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.

Claims

Claims
1 . A topical composition, characterized in that 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.
2. The topical composition according to claim 1 , characterized in that 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.
3. The topical composition according to any of the claims 1 to 2, characterized in that it is a cosmetic composition.
4. The topical composition according to claim 3, characterized in that the cosmetic composition is a skin care preparation.
5. The topical composition according to claim 3 or 4, characterized in that the cosmetic composition is in the form of a milk, lotion, hydrodispersion, foundation, cream, creamgel, serum, toner, mask or gel.
6. Use of niacinamide and alpha-arbutin for skin lightening, characterized that the weight-ratio of niacinamide to alpha-arbutin is selected in the range of 15 to 6, and more advantageously in the range of 12 to 8.
7. The use according to claim 6 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.
8. Use of niacinamide for enhancing the skin lightening activity of alpha-arbutin.
9. A method of lightening human skin, which comprises topically administering an effective amount of a topical composition according to any one of claims 1 to 5 to the appropriate skin area of a person in need of such treatment.
10. The method according to claim 9 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.
1 1 . A method of treating or preventing pigmentation disorders, which comprises topically administering an effective amount of a topical composition according to any one of claims 1 to 5 to the appropriate skin area of a person in need of such treatment.
12. The method as in claim 9 to 1 1 wherein from about 0.2 μg to about 200 μg of niacinamide and alpha-arbutin are applied per square centimeter of skin per day.
13. Niacinamide and alpha-arbutin for use in a topical pharmaceutical composition for the treatment and prevention of skin pigmentation disorders, characterized in that the amount of alpha-arbutin is selected in the range of 0.1 to 0.3 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 15 to 6.
PCT/EP2016/080465 2015-12-14 2016-12-09 Composition comprising niacinamide and alpha-arbutin for skin lightening WO2017102589A1 (en)

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102165565B1 (en) * 2019-07-22 2020-10-14 주식회사 오퍼스아시아 Cosmetic composition with excellent blemish and blemishes
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2522329A1 (en) * 2011-05-09 2012-11-14 DSM IP Assets B.V. Use of resveratrol and arbutin
CN103598993A (en) * 2013-11-05 2014-02-26 苏州冉新生物技术有限公司 Anti-freckle cosmetic
CN103919714A (en) * 2014-04-30 2014-07-16 广州品赫化妆品有限公司 Skin whitening composition

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104434705A (en) * 2014-12-26 2015-03-25 青蛙王子(中国)日化有限公司 Wash-free whitening mask cream for pregnant woman and preparation method of wash-free whitening mask cream

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2522329A1 (en) * 2011-05-09 2012-11-14 DSM IP Assets B.V. Use of resveratrol and arbutin
CN103598993A (en) * 2013-11-05 2014-02-26 苏州冉新生物技术有限公司 Anti-freckle cosmetic
CN103919714A (en) * 2014-04-30 2014-07-16 广州品赫化妆品有限公司 Skin whitening composition

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
"Gold caviar uv white lotion", GNPD; MINTEL, November 2009 (2009-11-01), XP002673825 *
DSM NUTRITIONAL PRODUCTS AG: "Alpha arbutin - Superior skin lightening enhancer for a perfect even skin tone", 20 June 2014 (2014-06-20), XP002759275, Retrieved from the Internet <URL:http://www.centerchem.com/Products/DownloadFile.aspx?FileID=6902> [retrieved on 20160628] *
NICO SMIT1 ET AL: "The Hunt for Natural Skin Whitening Agents", INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL, BASEL, CH, vol. 10, no. 12, 10 December 2009 (2009-12-10), pages 5326 - 5349, XP002656718, ISSN: 1422-0067, DOI: 10.3390/IJMS10125326 *
WENYUAN ZHU ET AL: "The Use of Botanical Extracts as Topical Skin-Lightening Agents for the Improvement of Skin Pigmentation Disorders", JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS. 75TH., vol. 13, no. 1, April 2008 (2008-04-01), US, pages 20 - 24, XP055284215, ISSN: 1087-0024, DOI: 10.1038/jidsymp.2008.8 *

Cited By (7)

* Cited by examiner, † Cited by third party
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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
CN115252899B (en) * 2022-09-13 2024-03-26 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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