CN104257515B - Glycine derivate having function of inhibiting melanogenesis and whitening composition using same - Google Patents
Glycine derivate having function of inhibiting melanogenesis and whitening composition using same Download PDFInfo
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- CN104257515B CN104257515B CN201410448969.5A CN201410448969A CN104257515B CN 104257515 B CN104257515 B CN 104257515B CN 201410448969 A CN201410448969 A CN 201410448969A CN 104257515 B CN104257515 B CN 104257515B
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Abstract
The invention discloses a glycine derivate having a function of inhibiting melanogenesis. The glycine derivate has the following structure shown in a general formula (I) in the specification, wherein R1 represents C1 to C4 alkyl, R2 represents hydrogen atoms or methyl, and n represents an integer from 1 to 6. The glycine derivate can be used as an effective component for whitening skins and can be applied to various whitening formula compositions; moreover, the glycine derivate is high in stability and is particularly applied to water-based cosmetic care product formulas with transparent appearances.
Description
The present invention is application number 201080002871.7, entitled " to there is the glycine for suppressing melanin to generate to spread out
It is biological and using its whitening constituent " application case divisional application, the applying date of original female case is on October 22nd, 2010.
Technical field
The present invention is with regard to a kind of glycine derivant, especially with regard to a kind of with the glycine for suppressing melanin to generate
Derivant and the whitening constituent using which.
Background technology
The generting machanism of general melanin (melanin), is considered as relevant with Tyrosinase (tyrosinase).Epidermis is thin
In born of the same parents, naturally occurring has Tyrosine (tyrosine), melanic predecessor, via Tyrosine → DOPA (Dopa) → DOPA quinone
(Dopaquinone) → dopachrome (Dopachrome) → melanin, in melanin reaction of formation process, Tyrosinase is attached most importance to
The ferment wanted, makes Tyrosine be converted into DOPA by the activity of its hydroxylase, is converted into DOPA by oxidasic activity many
Bar quinone.As long as epidermal melanocytes therefore can be effectively acted on, suppress melanic generation (melanogenesis),
Or suppress the material of melanic biosynthetic arbitrary process, you can as the effective ingredient of skin-whitening.Melanin is generated
First step for starting is to form DOPA quinone by Tyrosinase catalysis tyramine acid oxidase, as long as the activity for suppressing Tyrosinase is
The a series of reaction that whole melanin can be suppressed to generate, Tyrosinase inhibitor become one of effective ingredient of skin-whitening.
However, the effective ingredient of various skin-whitenings, which suppresses the mechanism that melanin is generated, and it is also not complete to be not quite similar
All clear Chu.The whitening main constituent being generally known, such as kojic acid (Kojic acid), vitamin C derivatives (ascorbic acid
) and arbutin (arbutin) etc. is all the compound of the known function of having and suppress Tyrosinase activity derivatives.
Kojic acid is unstable in the solution, and the program for causing formula manufacture is complicated (to be chatted with reference to United States Patent (USP) US6,306,376
State), and the allergy of skin can be caused when being applied to skin care product (with reference to Contact Dermatitis, Jan 95, Vol.42
(1), Page 9～13), the above all limits the application of its whitening formula.
Vitamin C is highly unstable, easily oxidation deterioration, therefore is usually used in whitening formula ascorbic derivative
Thing is lifting the stability of formula.But, remain a need for adding such as sodium sulfite (sodium hydrogen in its formula
Sulfite tranquilizer) or allotment buffer solution are mitigating the degree of formula oxidation stain.(U.S. Patent No. 6 is referred to,
The embodiment of 801, No. 050) however, product is easily caused as tranquilizer using sulfide the problem (reference of sharp aroma
The narration of US 6,020,367), therefore the method does not solve whitening formula simultaneously for requirement and the problem of color and abnormal smells from the patient.
Though arbutin has whitening effect, because its structure is the candy derivant (Glycosylated of hydroquinone
Hydroquinone), still easily change colour because fragrance phenolic group is aoxidized in formula, and cause the difficulty in formula manufacture.This
Outward, arbutin dissolubility in water is low and cause to apply the concentration in formula low, and the whitening effect for actually producing is low (to refer to day
This patent JP 2009-67691 publications), how the motion of Japanese Patent Laid-Open 2009-67691 publications uses arbutin
Rice dispersed particle, but it is more difficult in manufacture, and and product is inconvenient to use, but also is have be difficult to be absorbed by the skin to ask
Topic.
In U.S. Patent No. 6365135, disclose using amido phenol amide (amino phenol amide) derivant
As whitening agent, in addition in Japanese Patent Laid-Open 07-061905 and Unexamined Patent 07-233022, amido phenol amide is also disclosed
As whitening composition, derivant infers in document that because of Tyrosinase be a kind of polyphenol oxidase (polyphenol of cupric
Oxidase), these have phenol structure compound may be suppress Tyrosinase activity effective ingredient, may be with Tyrosine
The structural similarity of enzyme is relevant.But, its structure is with oxidizable fragrance phenolic group and its derivant.
In Japanese Laid-Open Patent Unexamined Patent 5-032533 publications, Unexamined Patent 6-345797 publications, Unexamined Patent
5-170637 publications etc., disclose the various two peptides with whitening effect.In document, the amino acid side chain for being constituted all has
Mercapto and its derivant or aromatic group or fragrance phenolic group and its derivant, disclosed two peptide is for melanic
Suppression mechanism is unclear, such as the two disclosed victory in the table 1 of Japanese Laid-Open Patent Unexamined Patent 5-170637 publications
Difference of the peptide to Tyrosinase suppression ratio, can from 3%～56%, as long as therefore not two peptide class compound, you can into
For good whitening effective ingredient.
However, when manufacturing in practice and applying skin-care product formula, in addition to considering the effectiveness of its whitening main constituent,
Need to consider which has stability in formula simultaneously, it is to avoid and the solvent in formula and other additives produce reciprocal action and lead
Cause formula to go bad, produce the problem of color and taste.There are mirror the problems referred to above, it is still necessary to the new whitening effective ingredient of exploitation, fits
Share in various skin-care product, such as cream, emulsion, gel, astringent etc., and there is in formula stability, to accord with
The demand of conjunction industry.
The content of the invention
In view of above-mentioned background of invention, in order to meet the requirement in industry, the one of the purpose of the present invention is to provide a kind of
Glycine derivant, which has the function of suppressing melanin to generate, can be applicable to various as the effective ingredient of skin-whitening
Whitening constituent.
And, an object of the present invention is to provide a kind of glycine derivant, and its structure does not have aromatic group, virtue
Fragrant phenol and its derivatives group, mercaptan and its derivatives group, and there is no optical activity, it is one possess oxidation stability and list
The derivant structure of one physiologically active.And there is in formula good color stability.
An embodiment of the invention, discloses a kind of glycine derivant, and which has the knot shown in following general formula (I)
Structure：
Wherein R1Represent the alkyl of C1～C4, R2Hydrogen atom or methyl are represented, and n represents 1～6 integer.
In one embodiment, above-mentioned glycine derivant is 3 (2- acetamidos-acetamido)-propanoic acid (3 (2-
Acetylamino-acetylamino)-propionic acid or Acetyl-Glycine- β-Alanine), with following institute
The structure of the chemical formula (II) shown：
In one embodiment, above-mentioned glycine derivant is 4- (2- acetamidos-acetamido) butanoic acid (4- (2-
Acetylamino-acetylamino)-butyric acid) or Acetyl-Glycine- γ-aminobutyric acid),
Structure with chemical formula (III) shown below：
In one embodiment, above-mentioned glycine derivant is [(2- acetamidos-acetyl group)-methyl-amido] acetic acid
([(2-Acetylamino-acetyl)-methyl-amino]-acetic acid) or Acetyl-Glycine-
Sarcosine), the structure with chemical formula (IV) shown below：
In one embodiment, it is added with the aqueous solution of 0.05～10wt% (weight ratio) glycine derivant and its buffers molten
Liquid, the light transmittance in the wave-length coverage of 420～500nm is more than 97%.Above-mentioned buffer solution is citric acid and its esters institute
Into.The above-mentioned aqueous solution and its buffer solution for being added with 0.05～10wt% (weight ratio) glycine derivant, in specific wavelength
During 440nm, its light transmittance is more than 98%.
According to another embodiment of the present invention, a kind of whitening constituent is disclosed, which is by addition 0.05wt%～10wt%
The above-mentioned glycine derivant institute of (weight ratio) is into the function of suppressing melanin to generate.More preferably constitute for above-mentioned whitening
Thing be by addition 0.5wt%～2wt% (weight ratio) above-mentioned glycine derivant institute into.
Glycine derivant of the invention, although do not know which suppresses the mechanism that melanin is generated, but test confirmation
With the function of suppressing melanin to generate.And, because its structure does not have aromatic group, fragrant phenol and its derivatives group, sulfur
Alcohol and its derivatives group, are a derivant structure for possessing oxidation stability, in whitening formula manufacture application and storage not
It is oxidizable rotten, it is with colour stability, and without obvious cytotoxicity, harmless for human body, and it is convenient to whitening constituent
Manufacture, application and storage, can lift the stability of formula.The glycine derivant of the present invention does not have optical activity (no in addition
Enantiomer), this represents that the glycine derivant of the present invention will not be caused because of the impurity for having other optical isomeric compounds
Physiologically active difference, the composition of all additions are all effective ingredient.Glycine derivant of the invention is particularly suitable for
It is applied to the aqueouss cosmetics formula of appearance transparent.
Description of the drawings
Nothing
Specific embodiment
For the present invention aforementioned and other technology contents, feature and effect, coordinate with reference to the preferable of schema following
In the detailed description of embodiment, clearly can present.In order to be able to thoroughly understand the present invention, will propose in following description
Detailed step and its composition.It is apparent that the execution of the present invention is not limited to the specific details is familiar with by this those skilled in the art.It is another
Aspect, it is thus well known that composition or step are not described in details, with the restriction for avoiding causing the present invention unnecessary.The present invention
Preferred embodiment will be described in detail it is as follows, but except these detailed description in addition to, the present invention widely can also be implemented in
In other embodiments, and the scope of the present invention is not limited, and which is defined by the scope of the claims afterwards.
The present invention is with regard to the compound as whitening effective ingredient.According to the research of the present inventor etc., two peptide is found
Whitening effect difference it is very big, although existing document discloses various (such as Japanese Laid-Open Patents of the two peptide with whitening effect
Unexamined Patent 5-032533 publications, Unexamined Patent 6-345797 publications, Unexamined Patent 5-170637 publications etc.), but
Because two peptide is combined into by 2 amino acids, the suppression carbonyl of two peptide is found containing a victory peptide bond, the present inventor etc.
The function of change, candy, oxidation etc., it is different with its structure, particularly in the activity or suppression polyphenol oxidase for suppressing Tyrosinase
Activity on, it is impossible to be only is determined by victory peptide bond, that is, the structure actually with two peptide, i.e. 2 amine of composition two peptide
The characteristic of base acid is relevant, it is impossible to merely judge that two peptide has the function of suppressing melanin to generate.Such as carnosine
(carnosine) antioxidant is known as, but does not have the effect for suppressing melanin to generate.
Additionally, such as non-patent literature Ge Ruili et al. (Inhibition of polyphenol oxidases
activity by various dipeptides,A.Girelli,E.Mattei,A.Messina,and A.Tarola,J.of
Agricultural and Food Chemistry, 2004,52.2741-2745) various two peptides are disclosed for polyphenol oxidase
The inhibitory action of the activity of enzyme, its result find that not all of two peptide all has to the activity of polyphenol oxidase and suppress to make
With.Furthermore, such as, in Japanese Laid-Open Patent Unexamined Patent 5-170637 publications, learn the two peptide of exposure to cheese by its table 1
The difference of amino acid enzyme inhibition rate, can be from 3%～56%, therefore the suppression Tyrosine enzyme viability of two peptide, not by victory peptide
Key determined, actually depends on the structure of two peptide compound.
An embodiment of the invention, discloses a kind of glycine derivant, and which has the knot shown in following general formula (I)
Structure：
Wherein R1Represent the alkyl of C1～C4, R2Hydrogen atom or methyl are represented, and n represents 1～6 integer.
In one embodiment, above-mentioned glycine derivant is 3 (2- acetamidos-acetamido)-propanoic acid (3 (2-
Acetylamino-acetylamino)-propionic acid) or Acetyl-Glycine- β-Alanine), with following
The structure of shown chemical formula (II)：
In one embodiment, above-mentioned glycine derivant is 4- (2- acetamidos-acetamido) butanoic acid (4- (2-
Acetylamino-acetylamino)-butyric acid) or Acetyl-Glycine- γ-aminobutyric acid),
Structure with chemical formula (III) shown below：
In one embodiment, above-mentioned glycine derivant is [(2- acetamidos-acetyl group)-methyl-amido] acetic acid
([(2-Acetylamino-acetyl)-methyl-amino]-acetic acid) or Acetyl-Glycine-
Sarcosine), the structure with chemical formula (IV) shown below：
In one embodiment, be added with 0.05～10wt% (weight ratio) present invention glycine derivant aqueous solution and
Its buffer solution, is more than 97% in the light transmittance of the wave-length coverage of 420～500nm.
Above-mentioned this is added with the aqueous solution and its buffer solution of 0.05～10wt% (weight ratio) glycine derivant, Yu Te
During a length of 440nm of standing wave, its light transmittance is more than 98%.
According to another embodiment of the present invention, a kind of whitening constituent is disclosed, which is by addition 0.05wt%～10wt%
The glycine derivant institute of the invention of (weight ratio) is into the function of suppressing melanin to generate.Above-mentioned whitening composition
Thing is by adding the glycine derivant of the invention institute of 0.1wt%～2wt% (weight ratio) into more preferable.
Glycine derivant of the invention, via cell experiment, learns with the effect for suppressing melanin to generate.
When being applied to skin, the glycine derivant of the present invention has the characteristic of low-molecular-weight, easily by percutaneous absorption, of the invention in addition
Glycine derivant there is no optical activity (no enantiomer), this represents that the glycine derivant of the present invention will not be because
There is the impurity of other optical isomeric compounds and cause physiologically active difference, the composition of all additions is all effective ingredient.
Below by example, the present invention is specifically described in more detail.First, the method that explanation prepares glycine derivant.
Example one, prepare 3 (2- acetamidos-acetamido)-propanoic acid (3 (2-acetylamino-acetylamino)-
Propionic acid or Acetyl-Glycine- β-Alanine)
By acetyl glycine (a；Ac-Gly-OH；3.77g, 32.2 mMs) and triethylamine (triethylamine；
6.7 milliliter；48.1 mMs) it is dissolved in 160 milliliters of tetrahydrofuran (THF), after being cooled to -10 DEG C, addition chloro-carbonic acid is different
Butyl ester (isobutylchloroformate；5.02g, 38.6 mMs).Mixed solution is stirred 1 hour at -10 DEG C.Separately
It is outer by β-alanine benzene methyl tosilate (e；H-β-Ala-OBzl.PTSA；11.26g, 32.0 mMs) and triethyl group
Amine (triethylamine；6.7 milliliter；48.1 mMs) be dissolved in 160 milliliters of tetrahydrofuran (THF) after, be added into
In above-mentioned mixed acid anhydride solution.Reactant mixture is stirred at room temperature overnight.Salt therein is filtered, to be vacuum dried removing
THF.By residue with tubing string chromatography purification, using ethyl acetate and heptane as eluant (eluent), obtain about
The intermedium f (Ac-Gly-beta-Ala-OBzl) of 5.95g.
After intermedium f is dissolved in 200 milliliters of tetrahydrofuran, add palladium-carbon catalyst (10wt%Pd/C), will be mixed
Compound is stirred overnight in the hydrogen gas atmosphere.Then, by Filtration of catalyst, by filtrate to be evaporated in vacuo, obtain about 2.49g
White powder g (yield 41.0%, purity>95%).The compound (hereinafter referred to as compound (II)) of gained is common with hydrogen-nuclear-magnetism
Vibration Meter is analyzed, and as a result obtains H1-NMR spectrum (1.84, s, 3H；2.35-2.38,t,2H；3.27-3.31,m,2H；3.61,d,
2H；7.85-7.87,t,1H；8.03-8.05,t,1H；12.22, s, 1H), confirm as 3 (2- acetamidos-acetamido)-the third
Sour (3 (2-acetylamino-acetylamino)-propionic acid), with the structure shown in above-mentioned chemical formula (II).
Example two, prepare 4- (2- acetamidos-acetamido) butanoic acid (4- (2-Acetylamino-acetylamino)-
Butyric acid) or Acetyl-Glycine- γ-aminobutyric acid)
By acetyl glycine (a；Ac-Gly-OH；2.52g, 21.6 mMs) and triethylamine (triethylamine；
5.0 milliliter；36.1 mMs) it is dissolved in 100 milliliters of tetrahydrofuran (THF), after being cooled to -10 DEG C, addition chloro-carbonic acid is different
Butyl ester (isobutylchloroformate；3.2g, 23.8 mMs).Mixed solution is stirred 1 hour at -10 DEG C.In addition
By γ-butylamine acid benzene methyl tosilate (e；H-γAbu-OBzl.PTSA；7.6g, 20.8 mMs) and triethylamine
(triethylamine；5.0 milliliter；36.1 mMs) be dissolved in 90 milliliters of tetrahydrofuran (THF) after, at -5 DEG C will
In its above-mentioned mixed acid anhydride solution of addition.Reactant mixture is stirred overnight at room temperature.Salt therein is filtered, it is dry with vacuum
Dry removing THF.By residue with tubing string chromatography purification, using ethyl acetate and heptane as eluant (eluent),
Obtain the intermedium i (Ac-Gly-GABA-OBzl) of about 2.6g.
After 2.6g intermedium i (Ac-Gly-GABA-OBzl) that purification is crossed is dissolved in 100 milliliters of tetrahydrofuran, add
Plus palladium-carbon catalyst (5wt%Pd/C, 0.26g), mixture is stirred overnight in the hydrogen gas atmosphere.Then, by being filtered to remove
Catalyst, by filtrate to be evaporated in vacuo, obtains white powder j (yield 43.3%, purity>95%).The compound of gained is (below
Referred to as compound (III)) with hydrogen-nuclear magnetic resonance analyser analysis, as a result obtain H1- NMR spectra (1.58-1.64, m, 2H；1.85,
s,3H；2.19-2.22,t,2H；3.04-3.08,m,2H；3.61-3.62,d,2H；7.81-7.83,t,1H；8.02-8.04,t,
1H；12.04, s, 1H), confirm as 4- (2- acetamidos-acetamido) butanoic acid (4- (2-Acetylamino-
Acetylamino)-butyric acid) or Acetyl-Glycine- γ-aminobutyric acid), with above-mentioned chemistry
Structure shown in formula (III).
Example three, preparation [(2- acetamidos-acetyl group)-methyl-amido] acetic acid ([(2-Acetylamino-
Acetyl)-methyl-amino]-acetic acid) or Acetyl-Glycine-Sarcosine)
By acetyl glycine (a；Ac-Gly-OH；4.10g, 35.0 mMs), alanine benzene methyl tosilate
(b；sarcosine benzyl ester p-toluenesulfonate；Sar-OBzl.PTSA；11.71g, 33.3 mmoles
You), triethylamine (triethylamine；5.58 milliliter；40.0 mMs), N- hydroxybenzotriazole (N-
hydroxybenzotriazole；HOBt；1.35g, 10.0 mMs) and N, N '-Dicyclohexylcarbodiimide (N, N '-
dicyclohexyl carbodimide；DCC；8.25g, 40.0 mMs) mixing in 200 milliliters of the tetrahydrofurans (THF)
It is stirred overnight.Mixed solution is filtered to remove into 1,3-Dicyclohexylurea (dicyclohexylurea；DCU), being vacuum dried removing
THF.Residue is dissolved in into 100 milliliters of ethyl acetate, using the aqueous cleaning 2 times of 100 milliliters of 10% citric acids,
The aqueous cleaning of 100 milliliters of 5% sodium bicarbonate 2 times, it is after 100 milliliters of saline (brine) cleans 2 times, dry with magnesium sulfate
It is dry, it is evaporated in vacuo, obtains the faint yellow oily intermedium c (c of about 9g；Ac-Gly-Sar-OBzl).
After oily intermedium c is dissolved in 200 milliliters of tetrahydrofuran, add palladium-carbon catalyst (10wt%Pd/
C), mixture is stirred overnight in the hydrogen gas atmosphere.Then, add methanol lysate, by Filtration of catalyst, then
Solvent is removed in vacuum.Concentrated residues thing is recrystallized with tetrahydrofuran, about 4.49g white powder d (yields are obtained
71.6%, purity>95%).The compound (hereinafter referred to as compound (IV)) of gained is analyzed with hydrogen-nuclear magnetic resonance analyser, as a result
H-NMR spectrum are obtained, peak value is as follows：(Major:1.86,s,3H；2.99,s,3H；3.96,d,2H；3.99,s,2H；
7.94,s,1H；12.6-12.9,m,1H.Minor:1.85,s,3H；2.81,s,3H；3.82,d,2H；4.10,s,2H；7.93,
s,1H；12.6-12.9, m, 1H), confirm as [(2- acetamidos-acetyl group)-methyl-amido] acetic acid ([(2-
Acetylamino-acetyl)-methyl-amino]-acetic acid) or Acetyl-Glycine-Sarcosine), tool
The structure having shown in above-mentioned chemical formula (IV), mixing of the gained compound for rotational isomeric thing (rotational isomers)
Thing.
The various characteristic tests of compound (II), (III) or (IV) are carried out below.
Cell white-skinned face function tests (Melaninogenesis inhibition test):
Cell white-skinned face function is tested using kojic acid (Kojic acid) as positive control group, and to compound (II), (III)
And (IV) and vitamin C derivatives carry out white-skinned face function assessment under the concentration of no cytotoxicity, test which and melanin is generated
Rejection ability.
Cytotoxicity is estimated using MTT Assay modes, all compounds for carrying out white-skinned face function test its for
3T3 fibroblasts and its half lethal dose of B16-F10 cells (LD50) are all higher than 5000mg/kg, its compound (II),
(III) and the safety in utilization of (IV) is equal to known using vitamin C derivatives of the safety without anxiety, belong to without obvious cell toxicant
Property, harmless compound
By mouse melanin tumor metastasiss cell (Mus musculus skin melanoma；B16-F10 96 holes) are flow into
In disk (96-well plate), contain 5000 cells (5000cells/well) in making every hole, 5% is incubated at 37 DEG C
CO2And 10% hyclone culture fluid (Fetal Bovine Serum Dulbecco'smodified Eagle's
medium；FBS DMEM).
Melanin production rate is defined as follows：
Wherein ODTRepresent the light absorption value that test sample solution under wavelength 405nm is measured using spectrophotometer, i.e. OD
(optical density) value, that is, using light absorption value during compound (II), (III) or (IV), ODBRepresent wavelength 405nm
The light absorption value of lower blank control group (blank control), ODNRepresent the light absorption value of negative control group under wavelength 405nm.Background control
Processed group of (negative control；Negative control group) comprising 0.1mg/ml Tyrosines (tyrosine) and 1 μM of melanotropin (α-
MSH, α-melanocyte stimulating hormone), blank control group includes 0.1mg/ml Tyrosines (tyrosine)
But α-MSH are not contained, test sample solution is first stored in the compound (II), (III) or (IV) of 5wt% without phenol red culture fluid
In (phenol red free DMEM), prepare the 5wt% containing 0.1mg/ml Tyrosines (tyrosine) and 1 μM of melanotropin
FBS culture fluid (5wt%FBS DMEM), (because 0.1mg/ml Tyrosines can be caused after being filtered with 0.22 μm of filter
Culture fluid supersaturation, so needing centrifugal filtration), test sample is prepared in the culture fluid, obtain test sample solution.
After cell converges (confluence) completely, be separately added in each hole 100 μ L test sample solution or
Reference sample (blank control group and background control group), after processing 3 days, adds the 1N sodium hydroxide (NaOH) of 100 μ L, concussion 10
After minute, the light absorption value (OD values) under its wavelength 405nm is measured.
Which is positives to control group for kojic acid (Kojic acid), (concentration 500ppm), with statistical method (Student ' s
T-test) analytical data, its P value are less than 0.05.Test result is shown in table one.
Table one
Kojic acid (positive control group 500ppm)：Melanin production rate %=33%
In table one, ascorbate glucoside represents ascorbic acid 2-glucoside (or AA2G), and ethyl is anti-bad
Hematic acid represents ethyl ascorbic acid, and ascorbic acid -2- magnesium phosphate represents ascorbic acid 2-phosphate
magnesium。
Color stability tests (Color stability test)
By testing sample (compound (II), (III) and (IV)) and reference sample be dissolved separately in water and pH value be 6 it is slow
Rush in liquid, become the solution containing 0.5wt% samples.PH value is the 0.1M citric acids and 16.2 that 6 buffer uses 3.8 milliliters
The mixed solution of the citrate of milliliter.Again 25 milligrams of sample is dissolved in wherein, is prepared containing the molten of 0.5wt% samples
Liquid.Color stability accelerated test is carried out in being then placed into 45 DEG C of baking ovens, ripple is measured with spectrophotometer after 14 days and 28 days
The light transmission rate of long 440nm, after testing 28 days and with efficient liquid phase chromatographic analyses instrument (HPLC/DAD (Diode array
Detection)) absorption intensity of the analysis of compounds (II), (III) and (IV) in 400～500nm wave-length coverages, its result show
Show.Table two represents that sample is dissolved in the result of water, table three represent sample be dissolved in pH value be 6 it is slow
Rush the result of liquid.
Table two
Table three
Hereinafter, illustrate the application of compound of the invention, but the invention is not restricted to those to match somebody with somebody using formulation Example
Square embodiment.
Formulation Example one is the following example for becoming astringent.
Astringent
Glycerol polymethacrylates：Glyceryl Polymethacrylate
Propylene Glycol：Propylene Glycol
PVM/MA：Polyvinyl methyl ethermaleic anhydride
Decadiene crosslinked polymer：Decadiene Crosspolymer
The poly- candy in Portugal：Sclerotium Gum
Hyaluronic acid sodium：Sodium Hyaluronate
Glycerol：Glycerin
Hydrolysis Lepidinm meyenii Walp root：Hydrolyzed Lepidium Meyenii Root
Methylisothiazolinone：Methylisothiazolinone
Octyl phenol polyethers -11：Octoxynol-11
Polysorbate20：Polysorbate 20
The mode of mixing, it is possible to use existing known method, such as first by the constituent mix homogeneously in A, then divide
Constituent that Jia Ru be in B, after stirring, the constituent in the C being pre-mixed is added in the mixture of A and B, is stirred
Mix uniform.
Formulation Example two is the following example for becoming whitening elite dew.
Whitening elite dew
Hydroxyethyl cellulose：Hydroxyethylcellulose
Flos Matricariae chamomillae extracts：Chamomilla Recutita(Matricaria)Flower Extract
The mode of mixing, it is possible to use existing known method, such as first by the constituent mix homogeneously in A, then divide
Constituent in C, D for being pre-mixed respectively, after stirring, is added the mixing of A and B by constituent that Jia Ru be in B
In thing, stir.
Formulation Example three is the following example for becoming skin youth emulsion (skin rejuvenation lotion).
Skin youth emulsion (skin rejuvenation lotion)
Spermol：Cetyl Alcohol
Glyceryl stearate：Glyceryl Stearate
PEG-75 stearates：PEG-75Stearate
Ceteth 20：Ceteth-20
Stereth -20：Steareth-20
Myristyl alcohol myristinate：Myristyl Myristate
Di-n-octyl sebacate：Dioctyl Sebacate
Different n-nonanoic acid Octyl Nitrite：Ethylhexyl Isononanoate
Macadimia nut oil：Macadamia Integrifolia Nut Oil
The mode of mixing, it is possible to use existing known method, for example, be first separately heated to the constituent in A and B
80 DEG C, stir, then the mixture of the constituent of B added the mixture of the constituent of A, stirring was lowered the temperature after 5 minutes,
Add sodium hydroxide to be neutralized, after temperature is down to 45 DEG C, adds the constituent in C one by one, stir.
In sum, glycine derivant of the invention, can be used as the effective ingredient for suppressing melanin to generate, can be with
It is matched with various skin care product, cosmetics, can is such as various kenels such as cream, emulsion, gel, astringent, as
The effective ingredient of whitening, its Efficacy experiments confirm the function of generating with suppression melanin, and because its structure does not have aromatic radical
Group, fragrant phenol and its derivatives group, mercaptan and its derivatives group, are a derivant structure for possessing oxidation stability, in
Oxidation deterioration is difficult when whitening formula manufacture application and storage, the stability with color and abnormal smells from the patient, and without obvious cytotoxicity,
It is harmless for human body.Additionally, the glycine derivant of the present invention does not have optical activity (no enantiomer), this represents this
The glycine derivant of invention will not cause physiologically active difference because of the impurity for having other optical isomeric compounds, Suo Youtian
Plus composition be all effective ingredient.And the manufacture storage in whitening formula product is used, the glycine derivant of the present invention all has
Standby good stability, is especially applicable to the aqueouss cosmetics formula of appearance transparent.
The above, is only presently preferred embodiments of the present invention, not makees any pro forma restriction to the present invention, though
So the present invention is disclosed above with preferred embodiment, but is not limited to the present invention, any to be familiar with this professional technology people
Member, in the range of without departing from technical solution of the present invention, when making a little change or modification using the technology contents of the disclosure above
For the Equivalent embodiments of equivalent variations, as long as being the content without departing from technical solution of the present invention, the technical spirit of the foundation present invention
Any simple modification, equivalent variations and the modification made to above example, still falls within the range of technical solution of the present invention.
Claims (7)
1. it is a kind of using the whitening constituent with the glycine derivant for suppressing melanin to generate, it is characterised in that its glycine
The addition percentage by weight of derivant is 0.05wt%～10wt%, wherein described glycine derivant is 3- (2- acetamides
Base-acetamido)-propanoic acid, the structure with chemical formula (II) shown below
2. it is a kind of using the whitening constituent with the glycine derivant for suppressing melanin to generate, it is characterised in that its glycine
The addition percentage by weight of derivant is 0.05wt%～10wt%, wherein described glycine derivant is 4- (2- acetamides
Base-acetamido) butanoic acid, the structure with chemical formula (III) shown below
3. it is a kind of using the whitening constituent with the glycine derivant for suppressing melanin to generate, it is characterised in that its glycine
The addition percentage by weight of derivant is 0.05wt%～10wt%, wherein described glycine derivant is [(2- acetamides
Base-acetyl group)-methyl-amido] acetic acid, the structure with chemical formula (IV) shown below
4. the use according to claim 1,2 or 3 has the whitening composition of the glycine derivant for suppressing melanin to generate
Thing, it is characterised in that the whitening constituent is 0.5wt%～2wt% as in claims 1 to 3 comprising addition percentage by weight
Glycine derivant described in any claim, the whitening constituent have the function of suppressing melanin to generate.
5. the use according to claim 1,2 or 3 has the whitening composition of the glycine derivant for suppressing melanin to generate
Thing, it is characterised in that：The whitening constituent also includes citric acid and its esters.
6. a kind of whitening of the non-therapeutic use using the whitening constituent with the glycine derivant for suppressing melanin to generate
Method, it is characterised in that：Using the whitening constituent as described in any claim in Claims 1 to 5 on the surface of skin.
7. according to claim 6 using the non-of the whitening constituent with the glycine derivant for suppressing melanin to generate
The method for whitening of therapeutic use, it is characterised in that：Whitening constituent as described in any claim in Claims 1 to 5
Form is selected from cream, emulsion, gel and astringent.
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| CN201410448969.5A CN104257515B (en) | 2010-10-22 | 2010-10-22 | Glycine derivate having function of inhibiting melanogenesis and whitening composition using same |
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| CN201080002871.7A CN103298778B (en) | 2010-10-22 | 2010-10-22 | Glycin derivatives inhibiting melanin production and whitening composition thereof |
| CN201410448969.5A CN104257515B (en) | 2010-10-22 | 2010-10-22 | Glycine derivate having function of inhibiting melanogenesis and whitening composition using same |
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| CN201080002871.7A Division CN103298778B (en) | 2010-10-22 | 2010-10-22 | Glycin derivatives inhibiting melanin production and whitening composition thereof |
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| JPH05170637A (en) * | 1991-12-25 | 1993-07-09 | Narisu Keshohin:Kk | Beautifying and whitening cosmetic |
| US6159485A (en) * | 1999-01-08 | 2000-12-12 | Yugenic Limited Partnership | N-acetyl aldosamines, n-acetylamino acids and related n-acetyl compounds and their topical use |
| RU2217196C2 (en) * | 2002-02-28 | 2003-11-27 | Небольсин Владимир Евгеньевич | Method for induction of cells differentiation |
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