CN114588068B - Composition with skin whitening and freckle removing effects - Google Patents
Composition with skin whitening and freckle removing effects Download PDFInfo
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- CN114588068B CN114588068B CN202210324558.XA CN202210324558A CN114588068B CN 114588068 B CN114588068 B CN 114588068B CN 202210324558 A CN202210324558 A CN 202210324558A CN 114588068 B CN114588068 B CN 114588068B
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- 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
- A61K8/676—Ascorbic acid, i.e. vitamin C
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
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- 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
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- 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
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- 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
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
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- 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
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
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- 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
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/59—Mixtures
- A61K2800/592—Mixtures of compounds complementing their respective functions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention discloses a composition with skin whitening and freckle fading effects, and relates to the technical field of cosmetics; the invention discloses application of a combination of tranexamic acid, ascorbyl glucoside, nicotinamide and hydroxyethyl piperazine ethane sulfonic acid in preparing a composition with skin whitening and freckle fading effects. The invention discovers that the combination of the tranexamic acid, the ascorbyl glucoside, the nicotinamide and the hydroxyethyl piperazine ethane sulfonic acid is added into a pharmaceutical composition or a cosmetic composition, so that the skin melanin generation amount can be effectively reduced, the skin pigmentation can be improved, and the effects of whitening and brightening the skin can be realized. Compared with the prior art, the combination has synergistic whitening effect, and simultaneously has better stability and efficacy than the prior art.
Description
Technical Field
The invention relates to the technical field of cosmetics, in particular to a composition with skin whitening and freckle fading effects.
Background
With the progress and development of society, the living standard of people is higher and higher, skin care products are more popular, and the whitening and anti-aging requirements in the efficacy of the skin care products are particularly vigorous.
Skin tone is primarily determined by the various pigments of the skin, of which melanin plays a major role. Skin darkening, spots, etc. are caused by excessive melanin secretion by melanocytes or uneven melanin distribution. So the modern skin care products mainly aim at melanin to realize the effects of whitening and spot-lightening.
The skin is exposed to ultraviolet radiation and the key enzyme for melanin production, tyrosinase, is activated, thereby promoting melanin production. Therefore, tyrosinase inhibitors are the focus of research in inhibiting melanogenesis. Another key component of skin pigmentation is the transport of melanosomes. Mature melanosomes are redistributed on the top layer of the skin by melanocyte dendrite mediated transport to surrounding keratinocytes and concomitant migration of keratinocytes. By promoting the exfoliation of the horny layer, the metabolism of melanin contained in horny cells can be promoted, and problems such as skin dullness and color spots can be improved. Therefore, melanin transport and metabolism are also the directions of interest for skin whitening research.
The skin whitening agents commonly used at present mainly comprise arbutin, kojic acid and derivatives thereof, ascorbic acid and derivatives thereof, hydroquinone, nicotinamide, tretinoin, fruit acid, azelaic acid, various herbal extracts and the like. The above components have whitening effect, but the mechanisms of the components are different, and the components have advantages and disadvantages when being singly used. Although there are whitening products with multiple whitening components on the market, the whitening products basically stay in the simple superposition of the components with the same mechanism, have insignificant advantages compared with the single components, or lack definite synergistic effect.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides a composition with the effects of whitening skin and lightening spots. The combination of the tranexamic acid, the ascorbyl glucoside, the nicotinamide and the hydroxyethyl piperazine ethane sulfonic acid provided by the invention can act on melanin generation, transportation and metabolism channels, has a synergistic whitening effect, and is superior to the prior art in stability and efficacy.
In order to solve the problems, the invention provides the following technical scheme:
in a first aspect, the present invention provides the use of a combination of tranexamic acid, ascorbyl glucoside, nicotinamide and hydroxyethylpiperazine ethane sulphonic acid in the preparation of a composition having skin whitening and spot lightening efficacy.
The compositions described herein include, but are not limited to, pharmaceutical compositions and cosmetic compositions, particularly cosmetic compositions, more particularly skin care cosmetic compositions.
Further, in the composition, the content of the tranexamic acid is 0.1-4%, the content of the ascorbyl glucoside is 0.01-2%, the content of the nicotinamide is 1-8%, and the content of the hydroxyethyl piperazine ethane sulfonic acid is 0.1-1%, based on the total weight of the composition.
Preferably, the composition comprises 0.4-3% of tranexamic acid, 0.1-2% of ascorbyl glucoside, 1-5% of nicotinamide and 0.5-1% of hydroxyethyl piperazine ethane sulfonic acid, based on the total weight of the composition.
The second hair side, the invention provides a composition with the effects of whitening skin and lightening spots, wherein the composition comprises a combination of tranexamic acid, ascorbyl glucoside, nicotinamide and hydroxyethyl piperazine ethane sulfonic acid.
The compositions described herein include, but are not limited to, pharmaceutical compositions and cosmetic compositions, particularly cosmetic compositions, more particularly skin care cosmetic compositions.
Specifically, in the composition of the invention, tranexamic acid, ascorbyl glucoside, nicotinamide and hydroxyethyl piperazine ethane sulfonic acid are used as whitening and spot-lightening compositions, wherein the tranexamic acid has the effects of inhibiting tyrosinase activity and inhibiting melanin generation. The external tranexamic acid (2-5%) has good tolerance and no serious side effects; the ascorbyl glucoside has the same physiological activity as L-ascorbic acid, can effectively remove ROS and inhibit melanin generation; nicotinamide acts on pigmentation mainly by inhibiting melanosome transport; hydroxyethyl piperazine ethane sulfonic acid can activate the activity of horny layer protease, mildly promote the exfoliating of horny layer, and further promote the melanin metabolism. According to the invention, experiments show that the combination of the tranexamic acid, the ascorbyl glucoside, the nicotinamide and the hydroxyethyl piperazine ethane sulfonic acid can effectively reduce the generation amount of skin melanin and improve skin pigmentation, so that the effects of whitening and brightening skin are realized. The composition of the present invention can significantly improve the efficacy of reducing skin melanin production compared to any three or two of tranexamic acid, ascorbyl glucoside, nicotinamide and hydroxyethylpiperazine ethane sulfonic acid, or to existing whitening spot-lightening compositions, indicating that the combination of tranexamic acid, ascorbyl glucoside, nicotinamide and hydroxyethylpiperazine ethane sulfonic acid has a synergistic effect, and also that the combination is not a simple replacement or superposition between existing whitening components.
Further, in the composition, the content of the tranexamic acid is 0.1-4%, the content of the ascorbyl glucoside is 0.01-2%, the content of the nicotinamide is 1-8%, and the content of the hydroxyethyl piperazine ethane sulfonic acid is 0.1-1%, based on the total weight of the composition.
Preferably, the composition comprises 0.4-3% of tranexamic acid, 0.1-2% of ascorbyl glucoside, 1-5% of nicotinamide and 0.5-1% of hydroxyethyl piperazine ethane sulfonic acid, based on the total weight of the composition.
When the composition of the present invention is a cosmetic composition, the composition of the present invention may optionally contain, in addition to the above-mentioned components, usual ingredients of the cosmetic composition including vehicles, surfactants, skin care active ingredients, cosmetic adjuvants and the like any ingredient known in the art, and the type and amount thereof may be selected according to specific needs. Typically, the usual ingredients are present in an amount of 1 to 95% by weight, based on the total weight of the composition.
In the present invention, such vehicles are known in the art and include, but are not limited to, diluents, dispersants or carriers, etc., including, but not limited to, ethanol, butylene glycol, dipropylene glycol, pentylene glycol, etc. The type and amount thereof can be selected by those skilled in the art according to actual needs. Typically, in the compositions of the present invention, the vehicle comprises 1-20% by weight of the total weight of the usual ingredients.
The surfactant is any type of surfactant commonly used in cosmetics and is used for reducing the surface tension of an interface, and the surfactant can achieve the purposes of cleaning, emulsifying and stabilizing a system. The surfactants include, but are not limited to, fatty acid soaps (e.g., sodium laurate, sodium palmitate, etc.), higher alkyl sulfates (e.g., sodium lauryl sulfate, etc.), N-acyl sarcosins (e.g., sodium lauroyl sarcosinate, etc.), higher fatty acid amide sulfonates (e.g., sodium lauryl methyl taurate, etc.), alkylbenzenesulfonates, higher fatty acid ester sulfates (e.g., sodium hardened coconut oil fatty acid glycerol sulfate, etc.), N-acyl glutamates, lauryl dimethylaminoacetic betaine, alkyl betaines, amidobetaines, sorbitan fatty acid esters (e.g., sorbitan monooleate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, glycerol polyglyceryl fatty acid esters (e.g., glyceryl monoerucate, glyceryl monostearate, glyceryl malate, etc.), PEG-fatty acid esters (e.g., PEG-distearate, ethylene glycol distearate, etc.), PEG-alkyl ethers (e.g., PEG-2-octyl ether), sucrose esters, etc., or a combination of more than one or more of these. For a particular surfactant, the type and amount thereof can be selected by one skilled in the art as desired. Typically, in the compositions of the present invention, the surfactant comprises from 0.5 to 50% by weight of the total weight of the usual ingredients.
Such skin care actives are known in the art and include, but are not limited to, moisturizers, skin conditioners, emollients, and the like. The humectants include, but are not limited to, one or more of glycerol, trehalose, sucrose, panthenol, propylene glycol, 1, 2-pentanediol, mannitol, glycerol polyether-26, rhamnose, raffinose, erythritol, polyethylene glycol-8, polyethylene glycol-32, methyl glucitol polyether-10, methyl glucitol polyether-20, PEG/PPG-17/6 copolymer, sodium polyglutamate, xylitol, urea, hydrolyzed ringlet, sodium polyglutamate, glycerol glucoside, PPG-10 methyl glucether, pullulanase polysaccharide, tremella polysaccharide, PPG-20 methyl glucether, and the like. Typically, in the compositions of the present invention, the humectant comprises from 1 to 35% by weight of the total weight of the usual ingredients.
The skin conditioner can be used for moisturizing, anti-wrinkle, freckle removing, acne removing, oil controlling and the like. The skin conditioning agents include, but are not limited to, one or more combinations of phytosterol/octyldodecanol lauroyl glutamate, turmeric root extract, ceramide 2, ceramide 3, hydrolyzed sodium hyaluronate, cholesterol, allantoin, birch bark extract, hydrogenated lecithin, arbutin, acetylphytosphingosine, resveratrol, pterocarpus marsupium bark extract, coleus forskohlii root extract, bisabolol, panthenol, allantoin, tetraisopalmitate ascorbate, piper nigrum seed extract, oxyphenyl propionamide benzoic acid, ubiquinone, pyridoxine dipalmitate, pyridoxine dioctate, retinol palmitate, tocopheryl acetate, oat kernel extract, and the like. Typically, in the compositions of the present invention, the skin conditioning agent comprises from 0.05 to 50% by weight of the total weight of the usual ingredients.
The emollients include, but are not limited to, one or more combinations of tri (ethylhexanoate), isopropyl lauroyl sarcosinate, caprylic/capric triglyceride, grape seed oil, white pool seed oil, shea butter, cetyl alcohol, dimethicone, pentaerythritol tetra (ethylhexanoate), olive oil, avocado oil, corn oil, dioctyl carbonate, homosalate, squalane, stearyl alcohol, isopropyl myristate, myristyl alcohol, hydrogenated polydecene, mao Ruilv fruit oil, sunflower seed oil, isohexadecane, jojoba oil, lanolin, paraffin, microcrystalline wax, beeswax, and the like. Typically, in the compositions of the present invention, the emollient comprises 0.05 to 50% of the total weight of the usual ingredients.
The cosmetic adjuvants include, but are not limited to, emulsifiers, thickeners, preservatives, fragrances, pH adjusters, and the like.
The emulsifier includes, but is not limited to, one or more of sorbitan olive oleate, stearyl polyether-21, PEG-60 hydrogenated castor oil, glyceryl stearate/PEG-100 stearate, PPG-13-decyltetradecylether-24, cetostearyl glucoside, polyglyceryl-10 myristate, cetostearyl glucoside, polyglyceryl-10 stearate, polyglyceryl-10 dioleate, and the like. The type and amount thereof can be specifically selected by those skilled in the art as desired.
The thickener includes, but is not limited to, one or more combinations of hydroxyethylcellulose, hydroxypropylcellulose, carbomer, xanthan gum, acacia, polyethylene glycol-14M, polyethylene glycol-90M, succinoglycan, acrylic/C10-30 alkanol acrylate cross-linked polymer, and the like. The type and amount thereof can be specifically selected by those skilled in the art as desired.
The preservative includes, but is not limited to, one or more of methylparaben, propylparaben, phenoxyethanol, benzyl alcohol, phenethyl alcohol, potassium sorbate, sodium benzoate, chlorpheniramine, and the like, and other preservative enhancers such as pentanediol, hexanediol, octanediol, p-hydroxyacetophenone, and the like. Typically, in the compositions of the present invention, the preservative comprises from 0.01 to 5% by weight of the total weight of the usual ingredients.
The pH adjuster includes, but is not limited to, one or more combinations of citric acid, sodium citrate, arginine, sodium hydroxide, potassium hydroxide, tromethamine, aminomethylpropanol, and the like. The type and amount thereof can be selected by one skilled in the art according to specific needs.
When the composition of the present invention is a pharmaceutical composition, the composition of the present invention may optionally contain, in addition to the above-mentioned components, usual ingredients of the pharmaceutical composition including any ingredients known in the art such as pharmaceutically active ingredients, and the type and amount thereof may be selected according to specific needs. The pharmaceutically active ingredient is an ingredient known in the art for whitening and lightening the spots. Typically, in the compositions of the present invention, the pharmaceutically active ingredient comprises from 0.05 to 85% by weight of the total weight of the usual ingredients.
The compositions of the present invention may be prepared by any suitable method known in the art. For example, the liquid may be prepared using a container such as a dissolution tank, an emulsifying pot, a disperser, or a transfer pump, which are commonly used in the art. During preparation, water-soluble substances are firstly put into a water-phase dissolution kettle, oil-soluble substances are put into an oil-phase dissolution kettle, and the temperatures of the two kettles are respectively heated to about 80 ℃, wherein the raw materials which are easy to agglomerate can be pre-dispersed by a disperser. After the dissolution is completed, the oil phase and the water phase are conveyed into an emulsifying pot, and are homogenized and emulsified for about 5 to 15 minutes. After the emulsification is completed, the temperature of the material is reduced to normal temperature, essence, preservative and the like are optionally added, and a proper amount of pH regulator is added to adjust the pH of the product as required. And filling and discharging after the relevant detection indexes are qualified.
The preparation method can be deleted or regulated according to the requirements of the dosage form. The cosmetic composition can be prepared into various dosage forms such as liquid, emulsion, cream or gel or various forms such as whitening and freckle-removing toning lotion, whitening and freckle-removing spray, whitening and freckle-removing emulsion, whitening and freckle-removing essence, whitening and freckle-removing BB cream, whitening and freckle-removing sun cream and the like.
In a third aspect, the present invention also provides a method for improving the whitening and spot-lightening efficacy of a composition, specifically: a combination of tranexamic acid, ascorbyl glucoside, nicotinamide and hydroxyethylpiperazine ethane sulfonic acid is added to the composition.
The method can remarkably improve the effect of the composition in reducing skin melanin generation.
The compositions described herein include, but are not limited to, pharmaceutical compositions and cosmetic compositions, particularly cosmetic compositions, more particularly skin care cosmetic compositions.
Compared with the prior art, the invention has the following beneficial effects:
the invention discloses application of a combination of tranexamic acid, ascorbyl glucoside, nicotinamide and hydroxyethyl piperazine ethane sulfonic acid in preparing a composition with skin whitening and freckle fading effects. The invention discovers that the combination of the tranexamic acid, the ascorbyl glucoside, the nicotinamide and the hydroxyethyl piperazine ethane sulfonic acid is added into a pharmaceutical composition or a cosmetic composition, so that the skin melanin generation amount can be effectively reduced, the skin pigmentation can be improved, and the effects of whitening and brightening the skin can be realized. Compared with the prior art, the combination has synergistic whitening effect, and simultaneously has better stability and efficacy than the prior art.
Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this application, illustrate and do not limit the invention, and together with the description serve to explain the principle of the invention:
FIG. 1 is a schematic representation of a sample of composition 3, compositions 7-9 of the present invention prior to illumination;
FIG. 2 is a schematic representation of the sample of composition 3, compositions 7-9 of the present invention after 1 month of illumination.
Detailed Description
The technical solutions in the embodiments will be clearly and completely described below with reference to the accompanying drawings and specific embodiments. It will be apparent that the embodiments described below are only some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
It should be understood that the terms "comprises" and "comprising," when used in this specification and the appended claims, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.
It is also to be understood that the terminology used in the description of the embodiments of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of embodiments of the invention. As used in the specification of the embodiments of the invention and the appended claims, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.
The components in the embodiment of the invention are calculated according to weight percentage; the starting materials in the examples of the present invention are all commercially available.
Specifically, the whitening and freckle-removing effect of the invention adopts a 3D skin model to verify the whitening effect, and the skin model and specific reagents adopted in the invention are as follows:
MelaKutis 3D melanin skin model (lot number: MS 220101), skin model culture broth (M-TA), supplied by Guangdong Boxi Biotechnology Co., ltd; PBS, bordetella bioengineering limited; sodium hydroxide, diethyl ether, absolute ethyl alcohol, national pharmaceutical group pharmaceutical company, inc; DMSO (dimethyl sulfoxide), sigma reagent company;
whitening and spot-removing composition: tranexamic acid, hunan Dongting pharmaceutical Co., ltd; nicotinamide, dissmann nutrition products Co., ltd; ascorbyl glucoside, hayashibiara co., LTD; hydroxyethyl piperazine ethane sulfonic acid, TAIWAN HOPAX CHEMS.MFG.CO., LTD.
Testing sample matrix composition: glycerol, feng Yi oil technologies (Dongguan); methylparaben, a company of chemical industry, clariant, china; carbomers, lu Bo, advanced materials company; isopropyl lauroyl sarcosinate, AJINOMOTO co., INC; tromethamine, ANGUS CHEMICAL COMPANY.
3-o-ethyl ascorbic acid, COSMOL co., LTD; sodium ascorbyl phosphate, ascorbic acid, dissman nutrition products Co., ltd; salicyl phytosphingosine wins the company special chemistry (Shanghai) limited; kojic acid, shanghai Source leaf Biotechnology Co.
Instrument: CO 2 Incubator (Thermo Fisher, 150I), ultra clean bench (SW-CJ-1F, antai air technologies Co., ltd., suzhou), UVB lamp (Philips), colorimeter (Dermalab, DSM II), digital display thermostat water bath (HH-4A, hezhou national electric appliance Co., ltd.), enzyme label instrument (BioTek, epoch), homogenizer, ai Ka instrument device Co., ltd.).
As described above, the whitening and spot-lightening effect of the present invention uses a 3D skin model to perform whitening efficacy verification, and the whitening efficacy verification is specifically an effect of improving the L-value of the skin and reducing the melanin content in the skin model.
Example 1: preparation of samples from the experimental and control groups
In this example, composition samples having the following formulations were prepared, respectively, wherein compositions 1 to 3, which are experimental groups of the present invention, and compositions 4 to 6, which are control group samples, and the specific compositions are shown in Table 1.
Table 1: composition 1-6 components and amounts (%)
Note that: AA2G is ascorbyl glucoside, HEPES is hydroxyethyl piperazine ethane sulfonic acid, tromethamine is used as a pH regulator to regulate the pH of the product, and the dosage can be regulated according to specific needs by a person skilled in the art; the water is deionized water commonly used in the cosmetic field.
The preparation method of the composition comprises the following steps:
1) 3g of glycerol and 0.2g of methylparaben are heated to 80 ℃ to dissolve the methylparaben completely; after cooling, adding 0.4g carbomer while stirring until the carbomer swells well; adding tranexamic acid, nicotinamide and HEPES according to the actual proportion of each test group composition, stirring and dissolving;
2) Preparing a 10% aqueous AA2G solution;
3) Adding 6g of isopropyl lauroyl sarcosinate into 1) the aqueous phase, and homogenizing for 3min while adding; adding the AA2G prepared in the step 2) according to the actual adding proportion of the composition of the test group, and continuing to homogenize for 2min;
4) Adjusting the pH of the final system to about 6 by using tromethamine; adding water to make up 100g, stirring uniformly and taking out the sample.
The whitening efficacy of compositions 1-6, specifically the effect of increasing the L-value of the skin and reducing the melanin content in the skin model, was verified.
The verification step of the whitening efficacy verification is as follows (the following example also employs the whitening efficacy verification method):
1. skin model preparation
Preparing a 6-well plate, adding 3.7mL of M-TA culture solution into each well, and transferring the model on Day3 (TA 3) of gas-liquid level culture, namely on the Day0 of model receiving, into the marked 6-well plate; each test groupRequiring 6 models, transferring all 6-well plates with models to CO 2 Culturing in incubator (37 ℃ C., 5% CO) 2 )。
UVB stimulation and sample treatment
From the Day of model reception (Day 0), the negative control group and the sample group (compositions 3 to 6) were subjected to UVB irradiation treatment (50 mJ/cm) daily 2 ) The blank group was not subjected to UVB irradiation, and only the culture medium was changed every day. The sample groups were treated twice at Day3 and Day5 respectively in such a manner that the skin model surface was uniformly smeared with a smear volume of 10 μl/time. After the model is continuously cultured for 7 days (Day 7), samples are collected and tested.
3. Test index and test method
1) L value test
The value L is white balance, the larger the value, the more white the color is biased. And detecting the L-value of the model after the apparent chromaticity detection is finished. The specific detection operation is as follows: the model is placed on a flat and hard white plane, the stratum corneum is placed upwards, a detection hole of the color difference meter is vertically aligned with the surface of the model for detection, reading is repeated three times for each model, and an average value is taken as the reading of the L-value of a single model.
2) Melanin content detection
Placing the model with the measured L value in a 1.5mL centrifuge tube, adding 1mL PBS buffer solution, vibrating for 3min by a vortex oscillator, centrifuging for 10min by a low-temperature high-speed centrifuge at 2000r/min, and discarding the supernatant; sequentially adding 200 mu L of distilled water, 500 mu L of absolute ethyl alcohol and 500 mu L of diethyl ether into a 1.5mL centrifuge tube, fully and uniformly mixing, standing at room temperature for 20min, centrifuging at 3000r/min for 5min, and discarding the supernatant; 1mL of 1mol/L NaOH aqueous solution containing 10% DMSO is added, and the mixture is heated in a water bath at 80 ℃ for 40min; 200 mu L of suspension is sucked into a 96-well plate by a pipette, and the absorbance value is detected at the wavelength of 405nm on an ELISA detector; and (3) using melanin with different concentrations as a standard substance, drawing a standard curve, and calculating the melanin content in the models of different sample groups.
4. Statistical analysis of results
Comparisons between groups were performed using t-test statistical analysis. Statistical analysis was double tailed. P <0.05 was considered to have significant differences (labeled as x), and P <0.01 was considered to have very significant differences (labeled as x).
The experimental results are shown in table 2.
Table 2: whitening efficacy test results of compositions 3-6
As shown by the test results in table 2, compared with the negative control, the composition 3 of the present invention can significantly increase the value of L of skin, reduce the melanin content in the skin model (p < 0.01), and meanwhile, the effect of the composition 3 of reducing the melanin content in the skin model is significantly better than that of the composition 4-6 (p < 0.01), which indicates that 4 components in the composition of the present invention have synergistic effects of synergistic whitening. Meanwhile, the composition 3 of the invention is obviously better than the effect of the combination of the tranexamic acid, the nicotinamide and the HEPES (composition 5), and the composition has a synergistic effect by adopting the combination of the tranexamic acid, the ascorbyl glucoside, the nicotinamide and the hydroxyethyl piperazine ethane sulfonic acid, and the combination is not simple superposition among the existing whitening components.
Of particular note, composition 3 of the present invention is a preferred embodiment of the present invention, but compositions 1-2 also significantly improved skin L values, reduced melanin content in skin models, and compositions 1-2 also significantly improved melanin content in skin models over compositions 4-6, as compared to compositions 4-6.
Example 2: in this example, in order to further verify that the whitening and spot-fading components of the present invention have a synergistic effect, control samples having the following formulations were prepared, respectively; wherein, compositions 7-9 are prepared by substituting AA2G in composition 3 of the invention with ascorbic acid or other ascorbic acid derivatives, and the specific compositions are shown in Table 3.
Table 3: the components and amounts (%)
The preparation method of the composition comprises the following steps:
1) 3g of glycerol and 0.2g of methylparaben are heated to 80 ℃ to dissolve the methylparaben completely; after cooling, 0.4g carbomer was added while stirring until the carbomer swelled well. Adding tranexamic acid, nicotinamide and HEPES according to the actual proportion of each test group composition, stirring and dissolving;
2) 10% aqueous 3-o-ethyl ascorbic acid solution, 10% aqueous sodium ascorbyl phosphate solution and 10% aqueous ascorbic acid solution were prepared, respectively.
3) 6g of isopropyl lauroyl sarcosinate was added to 1) the aqueous phase and homogenized for 3min while adding. Adding the ascorbic acid or ascorbic acid derivative solution prepared in the step 2) according to the actual adding proportion of the test composition, and continuing to homogenize for 2min;
4) Adjusting the pH of the final system with tromethamine; compositions 7 and 9 have a final pH of about 5; the final pH of the composition 8 is about 7 (the pH is adjusted according to the optimal pH of each component), 100g of water is added to be added, and the mixture is stirred uniformly and then discharged.
The stability and whitening efficacy of compositions 3, 7-9 were verified.
The stability verification steps are as follows:
samples of inventive compositions 3, 7-9 were placed in a window for 1 month (1W) of illumination, and the stability of the samples was observed. Specifically the color change of the composition, and the test results are shown in fig. 1 and 2.
As can be seen from fig. 1 and 2, the cosmetic composition 3 (sample 3) of the present invention did not undergo a significant change in color after 1 month of illumination; while both composition 7 (sample 7) and composition 8 (sample 8) turned significantly yellow (not visible in fig. 2 due to the grey scale treatment required for the picture), composition 9 (sample 9) turned reddish brown and the material was significantly thinner in constitution. The AA2G employed in the present invention is shown to have superior stability compared to ascorbic acid or other ascorbic acid derivatives, and is more suitable for cosmetic formulation applications.
In conclusion, the combination of the tranexamic acid, the ascorbyl glucoside, the nicotinamide and the hydroxyethyl piperazine ethane sulfonic acid has a synergistic effect, is not simple replacement of the existing whitening components, and has more excellent stability.
Example 3: in this example, in order to further verify that the whitening and spot-fading components of the present invention have a synergistic effect, control samples having the following formulations were prepared, respectively; wherein, composition 10 is prepared by substituting AA2G in composition 3 of the invention with kojic acid, composition 11 is prepared by substituting tranexamic acid in composition 3 of the invention with salicyl phytosphingosine, and the ratio of composition 11 is properly adjusted, and the specific compositions are shown in Table 4.
Table 4: composition 3, 10-11 and the amount (%)
Note that: the tranexamic acid, nicotinamide, HEPES and kojic acid in the composition 10 are the whitening efficacy compositions in certain whitening essence.
A method of preparing composition 10 comprising the steps of:
1) 3g of glycerol and 0.2g of methylparaben are heated to 80 ℃ to dissolve the methylparaben completely; after cooling, stirring, and scattering 0.4g carbomer until the carbomer swells well; adding tranexamic acid, nicotinamide and HEPES according to the actual proportion of the composition of the test group, stirring and dissolving;
2) Preparing 10% of a kojic acid aqueous solution;
3) Adding 6g of isopropyl lauroyl sarcosinate into 1) the aqueous phase, and homogenizing for 3min while adding; adding the kojic acid prepared in the step 2) according to the actual adding proportion of the composition of the test group, and continuing to homogenize for 2min;
4) The pH of the final system is adjusted to about 6 by using tromethamine, water is added to make up 100g, and the mixture is stirred uniformly to obtain a sample.
A method of preparing composition 11 comprising the steps of:
1) 3g of glycerol and 0.2g of methylparaben are heated to 80 ℃ to dissolve the methylparaben completely; after cooling, stirring, and scattering 0.4g carbomer until the carbomer swells well; nicotinamide and HEPES are added according to the actual proportion of the composition of the test group, and stirred for dissolution.
2) Preparing a 10% aqueous AA2G solution;
3) Heating 0.1G of salicyl phytosphingosine and 6G of isopropyl lauroyl sarcosinate to 40 ℃ and uniformly mixing, adding 1) the aqueous phase, homogenizing for 3min while adding, adding 2) the prepared AA2G according to the actual adding proportion of the composition of the test group, and continuously homogenizing for 2min;
4) The pH of the final system is adjusted to about 6 by using tromethamine, water is added to make up 100g, and the mixture is stirred uniformly to obtain a sample.
The whitening efficacy of compositions 3, 10-11 was verified.
Verification of whitening efficacy the procedure is described in example 1.
The experimental results are shown in tables 5 and 6.
Table 5: whitening efficacy test results of compositions 3 and 10
| Composition 3 | Composition 10 | |
| Tranexamic acid | 3 | 3 |
| AA2G | 1 | - |
| Nicotinamide | 2 | 2 |
| HEPES | 0.5 | 0.5 |
| Kojic acid | - | 1 |
| Melanin content | 12.21 | 22.29 |
| p-value vs composition 3 | - | 0.0001** |
| Value of L | 71.45 | 70.31 |
From the test results in table 5, it can be seen that the effect of the composition 3 of the present invention is significantly better than the whitening efficacy composition in the competitive whitening refinement in terms of reducing the melanin content (p < 0.01) and increasing the L value (p < 0.05).
Table 6: whitening efficacy test results of compositions 3 and 11
As can be seen from the test results of table 6, composition 3 of the present invention was significantly better than composition 11 (p < 0.01) of AA2G, nicotinamide, HEPES and salicyl phytosphingosine in comparative document 3 in terms of efficacy in reducing melanin content in skin model, while composition 3 also had better efficacy in increasing L values than composition 11.
In summary, the invention employs a combination of tranexamic acid, ascorbyl glucoside, nicotinamide and hydroxyethylpiperazine ethane sulfonic acid to have a synergistic effect, which is not a simple replacement between existing whitening components.
It is particularly noted that the composition of the present invention can also be prepared into cosmetics in other dosage forms, such as various dosage forms of whitening and spot-lightening lotion, whitening and spot-lightening spray, whitening and spot-lightening emulsion, whitening and spot-lightening essence, whitening and spot-lightening BB cream, whitening and spot-lightening sun cream, etc., and the effects of the cosmetics or pharmaceutical compositions in other dosage forms are the same as those demonstrated in the examples.
The foregoing has described in detail the technical solutions provided by the embodiments of the present invention, and specific examples have been applied to illustrate the principles and implementations of the embodiments of the present invention, where the above description of the embodiments is only suitable for helping to understand the principles of the embodiments of the present invention; meanwhile, as for those skilled in the art, according to the embodiments of the present invention, there are variations in the specific embodiments and the application scope, and the present description should not be construed as limiting the present invention.
Claims (5)
1. A composition having skin whitening and spot-lightening effect, characterized in that the composition contains 0.1 to 4% of tranexamic acid, 0.01 to 2% of ascorbyl glucoside, 1 to 8% of nicotinamide, and 0.1 to 1% of hydroxyethylpiperazine ethanesulfonic acid, based on the total weight of the composition, and the composition uses only tranexamic acid, ascorbyl glucoside, nicotinamide and hydroxyethylpiperazine ethanesulfonic acid as active substances having skin whitening and spot-lightening effect.
2. The composition according to claim 1, wherein the tranexamic acid is present in the composition in an amount of 0.4 to 3%, the ascorbyl glucoside is present in an amount of 0.1 to 2%, the nicotinamide is present in an amount of 1 to 5%, and the hydroxyethylpiperazine ethanesulfonic acid is present in an amount of 0.5 to 1%, based on the total weight of the composition.
3. The composition according to any one of claims 1-2, wherein the composition is a pharmaceutical composition or a cosmetic composition.
4. A method for improving the whitening and spot-lightening efficacy of a composition, characterized in that 0.1 to 4% of tranexamic acid, 0.01 to 2% of ascorbyl glucoside, 1 to 8% of nicotinamide and 0.1 to 1% of hydroxyethylpiperazine ethane sulfonic acid are added to the composition based on the total weight of the composition, and the composition uses only tranexamic acid, ascorbyl glucoside, nicotinamide and hydroxyethylpiperazine ethane sulfonic acid as active substances having the whitening and spot-lightening efficacy.
5. The method of claim 4, wherein the tranexamic acid is present in the composition in an amount of 0.4-3% based on the total weight of the composition; the content of the ascorbyl glucoside is 0.1-2%; the content of nicotinamide is 1-5%; the content of the hydroxyethyl piperazine ethane sulfonic acid is 0.5-1%.
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