CN100389743C - Thermal shock protein generation promotion component and skin beauty and white applicat composition - Google Patents
Thermal shock protein generation promotion component and skin beauty and white applicat composition Download PDFInfo
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- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
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Abstract
A composition for external application to the skin is characterized by containing a component accelerating the formation of heat shock protein, and 3,4,5-trimethoxycinnamic acid thymolester of the formula(1) as a component inhibiting the formation of melanin, as well as a component inhibiting the inflammation caused by ultraviolet rays.
Description
Technical field
The present invention relates to a kind of heat shock protein and generate the promotion composition, and a kind of skin-whitening preparation composition for external use, the effective ingredient of this skin-whitening preparation composition for external use comprise above-mentioned heat shock protein generate promote composition, as the following Chemical formula 1 that is used to suppress to form the melanic composition of skin pigment material represent 3,4,5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester and being used to suppresses the skin irritation that ultraviolet causes or the composition of inflammation.
Chemical formula 1
Dermatologic preparation composition provided by the invention, comprise and be used for suppressing to form melanic composition, be used to suppress the composition of inflammation and be used to promote the synthetic composition of heat shock protein, therefore have the more outstanding effect of improving cutaneous pigmentation than including only the skin preparations for extenal use that suppresses the melanic composition of formation.
Technical background
The skin-color of human body is according to as melanin, and the human body constituent of colors such as carotene and hematochrome decides, wherein melanic contribution maximum.Melanin is the pigment cell that basal layer exists in the epidermis of skin--synthetic in the-melanocyte, and in the horn cell around transferring to by the form of melanosome and show skin color.The melanin of Sheng Chenging is distributed to the epidermis of skin equably and cuts off ultraviolet like this, and the following skin organ of protection corium is controlled the free radical of generation in the skin organism etc. simultaneously, range protein and cytogenetics in the protection skin.
But, by staying in the skin in the certain hour of melanin before the keratinization process by Skin Cell drops to the outside that various skin harmful factors are generated, so meetings such as melanotic nevus that the too much melanin that generates such as a lot of people note or freckle bring worry to the people.What take place in skin is melanic synthetic by being plain aminoacid of the happy mattress of Thailand or dihydroxyphenylalanine (DOPA) in the catalyst and the oxidizing process manufacturing as substrate by enzymes such as tryrosinases, can more increase this melanic generation when generating a lot of free radicals on the skin or inflammatory reaction is arranged or be subjected to ultraviolet infringement etc.
Being used for suppressing to form melanic composition is as benzene phosphorus diphenol, the polyhydroxy benzenes phenolic compounds of resorcinol etc., kojic acid, vitamin E, ascorbic acid usp/bp, hydroquinone etc.But its major part is to make the effect that participates in forming melanic tryrosinase invalid and make the inhibitory action of enzymatic activity be applicable to skin together by self antioxidant activity, can have chafe simultaneously or make to occur toxic shortcoming on the Skin Cell.Especially, the polyhydroxy benzenes phenolic compounds generates benzoquinone owing to after the easy oxidation of tryrosinase, so occur fatal toxicity on the Skin Cell.And foregoing chemical compound with antioxidant activity actually can not be guaranteed the safety of material itself when being applicable to the external preparation for skin dosage form and has the problem of tone variations or flavor change.
On the other hand, organism is during by thermal shock, and organism responds to it by its physiological change.Promptly, needed physiological change takes place in order to overcome new pressure environment, embody by adjusting total hereditary son, just restore in the time of restoring endoglobular degeneration albumen (denatured protein), the variation that the back is given back normal condition cell takes place in the time of can not restoring to decompose.At this moment the protein of Sheng Chenging be called heat shock protein (heat shock protein, HSP) or stress protein (stress protein) (Crit.Rev.Biochem., 18,239 (1985), Microbiol.Rev., 57,402 (1993)).To be subjected to heat be high-temperature to cell then; oxidisability pressure (Proc.Natl.Acad.Sci.USA.; 83; 8059 (1986)); nutrient restriction (J.Bacteriol.; 172; 7157 (1990)); (Arch.Microbiol. is impacted in infiltration; 150; 564 (1988)); heavy metal; ultraviolet radiation; DNA damage agent (Proc.Natl.Acad.Sci.USA.; 78; 5749 (1981)) and during the pressure of viral infection etc.; cell in order to protect own from coliform; bacillus subtilis prokaryotes such as (BacillusSubtilis) is to yeast; fruit bat; very general manufacturing heat shock protein (The biology of heat shock proteins and molecular chaperones.ColdSpring Harbor Laboratory Press till the high biology such as people; (1994); Stress proteins in biology and medicine; Cold Spring Harbor Laboratory Press; (1990); Cell Biology and Toxicology; 11,161 (1995)).Heat shock protein exists in all organisms very at large, some heat shock proteins are not only also dynamic equilibrium and the metabolism that keeps cell to be played very important (Proc.Natl.Acad.Sci.USA. under pressure environment but also under normal condition, 82,6455 (1985)).The main kind of heat shock protein comprises HSP 100 sections, HSP 90 sections, HSP 60 sections, HSP 47, HSP 33 and HSP 70 sections, wherein said HSP (the Trends Biochem.Sci. of 100 sections, 21,289 (1996)) be responsible for pyritous patience (thermostability), promote the decomposition (protein decompositions) of substrate in the cell and adjustment function such as to transcribe; Described HSP (the The biology of heat shock proteins and molecularchaperones.Cold Spring Harbor Laboratory Press of 90 sections, (1994)) in Cytoplasm and retinoic acid (retinoic acid), steroid receptor form complex, relevant with the mechanism of action of these signaling molecules (signal molecules), work with the function of adjusting the several tyrosine kinase (tyrosinekinase) that are encoded according to oncogene and the adjustment factor of detoxify protein process; Described HSP 60 sections (Nature, 355,33 (1992)) form in organelle and participate in Protein Folding and combination in the oligomer process after the synthetic protein transduction of Cytoplasm moves on to mitochondrion; Described HSP 47 (Lasers Med.Sci.16,192 (2001)) participates in the set and the transmission of collagen; Described HSP 33 (FEBS Lett., 489,19 (2001)) just makes induction when increasing active oxygen in cell, the protein that discharges according to active oxygen optionally in conjunction with after with its repairing; Described HSP 70 sections (EMBO J.20,446 (2001)) work by pressure sensitive, and the communicating path of inducing cell increment signal is worked as a kind of brake.Derivative maximum heat shock protein is HSP 72 when being stressed, its carry out proteinic synthetic, organella is passed on proteinic effect in cell.But along with the inducibility of the increase HSP 72 at age can reduce (Br.J.Dermatol., 134,1035 (1996)) gradually.HSP 72 is used to prevent proteinic cohesion and Denatured protein is returned to normal condition.The HSP 72 that is reported as too much production in a lot of papers can cut off according to thermal shock, chemical stimulation, ultraviolet radiation, active oxygen, the inductive apoptosis of TNF-α (Mol.Cell Biol., 22,7721 (2002)).
Summary of the invention
For this reason, inventor's conduct of the present invention obviously improves skin irritation and the cytotoxicity and the instable countermeasure of solution in the cosmetics dosage form of existing whitening agent, developed and comprised and do not rely on antioxidant effect and performance whitening effect and doing one's utmost suppresses the chemical compound 3 that melanin generates, 4,5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester several new materials such as (Chemical formula 1s).Further, illustrated in these chemical compounds especially 3,4, though 5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester has outstanding inhibition to form the melanin effect, but different with existing whitening agent, not to suppress to form melanin, but embody (International Pigment Cell Conference by restraint of tyrosinase itself by antioxidation, Netherlands, 2002).
When but skin formed melanin, the unlike signal that stimulates for the melanocyte synthesis of melanin worked, thus unsuitable control these the time be difficult to the resultful whitening effect of expectation.Especially reactive very high active oxygen (ROS; Reactive Oxygen Species) and the bio-tissue of radical damage such as cell membrane or DNA, can bring out and stimulate and inflammation.
The factor of mainly carrying disease germs of bringing out inflammation is interleukin-1 (IL-1), interleukin 8 (IL-8), prostaglandin (Prostaglandin), also has histamine (Histamine) etc., these also are to stimulate melanocyte and bring out melanic generation, recently to as to cross like this research of pigment heavy outstanding (PostinflammatoryHyperpigmentation) after the inflammation also very active.Therefore, be, use the Fructus Rubi corchorifolii Immaturus extract the result who suppresses or weaken the active component broad research of inflammation, the blue berry extract, the blackberry extract, when cranberry extract, Fructus Fragariae Ananssae extract etc., finding that the improvement that stimulates and inflammation generate suppresses excellent.
On the other hand; heat shock protein is when cell suffers heat to be the pressure of high temperature, oxidisability pressure, nutrient restriction, infiltration impact, heavy metal, ultraviolet etc.; cell is protein (Cell Biology and Toxicology, 11,161 (1995)) that make in order to protect own.Maximum inductive heat shock proteins are HSP 72 when being stressed, it carries out the proteinic effect of synthesizing, protein being communicated to organella in the cell, and prevent proteinic cohesion and Denatured protein be returned to normal condition, too much the HSP 72 that produces can cut off thermal shock, chemical stimulation, ultraviolet radiation, according to the inductive apoptosis of TNF-α (apoptosis) etc.
Therefore, need research when skin is exposed at as strong pressures such as ultraviolet, to forming the generation of the burn cell of following (sun burn cell) or the active component that apoptosis can be responded effectively with melanin.This is studied the heat shock protein generation that obtains widely promotes the result of composition to be ectoin, Salix alba extract; yeast extract, Semen Pisi sativi extract, kayasenegalensis extract; caffeic acid, p-coumaric acid etc. can promote the synthetic of heat shock protein and the protection Skin Cell.
And, the present inventor is studying effective method for whitening and is whitening with in the compositions, as 3 of Melanin inhibitor, 4, additional composition that is used to suppress skin irritation or inflammation and heat shock protein generate discovery when promoting to use behind the composition can to increase the sense of stability and the whitening effect of skin also unexpectedly good in the 5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester.
Therefore, one object of the present invention is to provide the material that can protect cell when skin suffers as ultraviolet or thermal pressure--the generation of-heat shock protein promotes composition.
Another object of the present invention is to provide and contains 3,4,5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester, the composition that suppresses skin irritation or inflammation and heat shock protein generate and promote skin-whitening preparation composition for external use composition, that have more outstanding whitening effect.
The invention provides a kind of when skin suffers as ultraviolet or thermal pressure; can respond effectively with melanin and form the generation of the burn cell (sun burn cell) follow or apoptosis and protect the cell activity material; be that thermal shock protein generates the promotion composition; it comprises being selected from by ectoin of more than one, Salix alba extract, yeast extract; Semen Pisi sativi extract; the kayasenegalensis extract, the component in the group that caffeic acid and p-coumaric acid are formed.
And, the invention provides a kind of above-mentioned heat shock protein generation promotion composition, 3 that comprises, 4,5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester and skin-whitening preparation composition for external use composition, that can improve whitening function that is used to suppress skin irritation or inflammation.
As the effective ingredient that promotes that heat shock protein generates, it comprises ectoin, Salix alba extract, yeast extract, Semen Pisi sativi extract, kayasenegalensis extract, caffeic acid, p-coumaric acid etc. according to of the present invention.
And, according to according to the present invention as the effective ingredient that suppresses synthesis of melanin, comprise that following Chemical formula 1 represents 3,4,5-trimethoxy cinnamic acid thymol ester compounds.
[Chemical formula 1]
In addition, comprise especially with 3,4 as effective ingredient at the composition that is used for suppressing or weaken skin irritation or inflammation, the Fructus Rubi corchorifolii Immaturus extract that 5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester is complementary, blue berry extract, blackberry extract, cranberry extract, Fructus Fragariae Ananssae extract etc.
The gross weight of relative compositions contains the heat shock protein generation promotion composition of 0.0001～20 weight % in the skin-whitening preparation composition for external use provided by the invention, preferably contains 0.001～5 weight %.Can not generate heat shock protein effectively during less than 0.0001 weight %, can not keep stable dosage form when surpassing 20 weight % and be not suitable for.
In addition, as represent with Chemical formula 13,4,5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester, the relative gross weight of compositions, its content is 0.0001～5 weight %, preferred 0.001～1 weight %.Can not suppress melanic formation effectively during less than 0.0001 weight %, bring out cytotoxicity when surpassing 5 weight % and be not suitable for.
In addition, as the composition of skin irritation that suppresses to bring out and inhibition inflammation by ultraviolet, the gross weight of relative compositions, its content is 0.0001～30 weight %, preferred 0.001～10 weight %.Can not suppress inflammation effectively during less than 0.0001 weight %, bring out as variable color and dosage form stability problem such as spoiled being not suitable for when surpassing 30 weight %.
The specific embodiment
Below, illustrate in greater detail the present invention.
Generate the ectoin that promotes composition and use according to the present invention as heat shock protein; the Salix alba extract; yeast extract; Semen Pisi sativi extract; the kayasenegalensis extract, caffeic acid, p-coumaric acid etc.; when cell suffers various pressure, promote heat shock protein synthetic in order to protect cell.Especially the cell of young healthy is made the very capable of heat shock protein; oneself avoid external impact so can protect; but it makes the ability reduction of heat shock protein old and feeble cell; can increase UV-induced melanin and form and damaging cells, also bring out (Photo-ageing) problem of promotion " photoaging " thus.Though cytoprotective Research on effect and the skin aging correlational study to heat shock protein occurs with the important research theme recently, up to the present also do not deliver the result of study relevant with the effect that helps to whiten.
And, form 3 of inhibition composition use according to the present invention as melanin, 4,5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester is different with the existing whitening agent that depends on antioxidation, it is to suppress the new mechanism material that melanin generates as the embodiment that is used for that suppresses to participate in the synthetic tryrosinase of melanin.Therefore, when existing a lot of whitening agents took place as variable color or physical change such as spoiled, in contrast, the present invention can make the dosage form of relative improvement stability.Moreover, also confirm as can not bring out cytotoxicity or skin irritation, sensitization, variability etc. to the very safe composition of skin.
In addition, by screening the raw material of about kind more than 350, consequently, suppress the Fructus Rubi corchorifolii Immaturus extract that composition uses, blue berry extract, blackberry extract according to of the present invention as skin irritation and inflammation, cranberry extract, Fructus Fragariae Ananssae extract etc. are judged as skin irritation and inflammation alleviation effects fitst waterly, the Kallidin I (Bradykinin) of especially suppress to participate in pain, erythema, itching etc. and the effect of P material (Substance P).In detail, these extracts can be suppressed at the secretion according to Kallidin I (Bradykinin) and P material (Substance P) excretory inflammatory cytokine (Cytokine) IL-6 and IL-8 of Skin Cell and neuronal cell line.Wherein the Fructus Rubi corchorifolii Immaturus extract can suppress the erythema phenomenon that vitamin A causes, also can relax the skin irritation of the lactic acid (Lactic acid) of one of the surfactant SLS (sodium lauryl sulphate) that is used in detergent and 'alpha '-hydroxy acids.On the other hand, according to the result of nearest research, the new research field that stimulates the cutaneous pigmentation phenomenon that occurs is in succession received much concern, but utilize the exploitation of the skin-whitening external agent of these phenomenons also not carry out actively.
In the present invention, heat shock protein generates and promotes composition, melanin to form inhibition composition 3,4,5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester and inflammation are suppressed to phase-splitting and join mutually, therefore use 3 with compositions than only as whitening, 4, the whitening effect during 5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester is more outstanding.
Skin-whitening preparation composition for external use of the present invention not only embodies as restraint of tyrosinase when suppressing the melanin generation; and can prevent the skin irritation of external pressures such as ultraviolet and the pigmentation of inflammation; promote the synthetic and protection cell of heat shock protein and use with the purpose of healthy skin; therefore without particular limitation to its dosage form; it for example can be toner/smoothing toner; the nutrition astringent, massage cream, nourishing cream; nutritional solution; foundation cream, water-setting reveals; the cosmetic material dosage form of protective skin cream or facial film form also can be as skin care liquid; ointment; gelinite, vanishing cream, the percutaneous dosage form of muffin or spray form.
And in the preparation composition for external use of each dosage form, other compositions beyond the above-mentioned required composition add according to the cooperation that the dosage form or the application target of external agent can be suitable.
Below, enumerate some test examples and dosage form example and illustrate in greater detail the present invention.But the present invention not merely is limited in these example scopes.
" test example 1 " synthetic increase effect of heat shock protein in keratinocyte
The proteinic synthetic degree of thermal shock is to measure according to Western blotting (Westernblot) method in the keratinocyte.Put into 5 * 10 from the isolating keratinocyte of people's epidermal tissue in the lining, each hole (well) of 6-culture vessel (well plate)
5The cells of quantity (cell) cultivated 24 hours in keratinocyte culture fluid (Keratinocyte growth media, Clonetics, BioWhittacker company, MD, the U.S.) lining the back.After getting rid of culture medium, above-mentioned keratinocyte is changed with the culture medium that comprises 7 kinds of substances of putting in order as following table 1.And, for relatively, in 44 ℃ of in the past heat shock protein formation conditions to keratinocyte heating 30 minutes.After 24 hours, in cell, add cytolysis buffer agent (Lysis buffer, 20mM Tris-HCl, pH7.5,150mM NaCl, 1mM Na after getting rid of culture medium and using the PBS washed twice
2EDTA, 1mM EGTA, 1%Triton, 2.5mM Sodiumpyrophosphate, 1mM β-glycerophosphate, 1mM Na
3VO
4, 1 μ g/ml leupeptin, 1mM PMSF) and dissolving.Dissolve and carried out ultrasonic grinding in back about 10 seconds, at 4 ℃, 10,000G carries out centrifugalize in five minutes, and after obtaining supernatant, determines proteinic amount.Lining, polyacrylamide gel body 10% (SDS-PAGE gel) each hole, lining (well) adds the protein of 10 μ g and is launching (running) in the 125V after 90 minutes, separated protein is moved on to nitrocellulose filter membrane (NitrocelluloseMembrane), at Tris buffer solution (TBST, Tris-Buffered Saline containing 0.05%Tween 20) lining is reacted more than one hour with the first antibody (primary antibody) of suitably dilution, described Tris buffer solution comprises polysorbas20 (the Tween 20) (Tween20 that contains 5% skim milk (nonfat milk), Uniqema company, Britain).After TBST washing three times, in conjunction with the horseradish peroxidase (HRP that suitably dilutes; Horse radish peroxidase) second antibody (secondary antibody) was reacted more than one hour.After TBST washing three times, add suitable substrate (substrate) color development.The color development degree is to use densimeter (Densitometer) to measure its area, uses with the fiducial value of matched group and represents.With the heat shock protein synthetic ratio of the keratinocyte that do not heat is 100% to show relative synthetic ratio.
[table 1]
| Substances | Concentration (%) | Heat shock protein synthetic ratio (% contrast) |
| Heat (Heat) | - | 272 |
| Ectoin | 0.20 | 168 |
| The Salix alba extract | 0.01 | 143 |
| Yeast extract | 0.10 | 223 |
| Semen Pisi sativi extract | 0.10 | 180 |
| The kayasenegalensis extract | 0.10 | 209 |
| Caffeic acid | 0.001 | 140 |
| The p-coumaric acid | 0.001 | 151 |
Can confirm ectoin from above-mentioned table 1, the Salix alba extract, yeast extract, Semen Pisi sativi extract, kayasenegalensis extract, caffeic acid, has the heat shock protein synthetic effect with the p-coumaric acid, especially yeast extract, the kayasenegalensis extract, the synthetic effect of the heat shock protein of Semen Pisi sativi extract is very outstanding.
Melanin in " test example 2 " melanin cellulation generates and suppresses effect
3,4, melanin generation inhibition degree is to measure according to the Dooley method in the cell of 5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester.Used cell is to use the Mel-Ab cell line that obtains from the pigment cell of skin of C57BL/6.Cultivation is to contain 10% Bovine Placenta serum, 100nM 12-O-14 (alkane) acyl Phobol-13-acetate (12-O-Tetradecanoyl Phobol-13-Acetate), in the DMEM culture medium of 1nM cholera toxin (Cholera Toxin) 37 ℃, 5%CO
2Carry out under the condition.The Mel-Ab cell of cultivating is used same numeral (1 * 10 after with insulin (Trypsin)-EDTA separation of 0.25% again
5Cells/well) be attached to 24-culture vessel (well plate) lining, changed with the culture medium that contains this chemical compound of 0.01% in continuous three days since second day then.And, for relatively, in the past the whitening agent composition---kojic acid is tested, also carry out to 3,4 the test that 5-trimethoxy cinnamic acid and thymol (Thymol) are handled respectively.Handled with 1N NaOH later in the 5th day and melt the melanin that comprises in the cell, by determine melanic amount at the absorbance measurement of 400nm, its result is as shown in table 2 below.
[table 2]
| Substances | Melanin production rate (% contrast) |
| Kojic acid | 75.0 |
| 3,4, the 5-trimethoxy cinnamic acid | 96.3 |
| Thymol | 94.5 |
| 3,4,5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester | 47.8 |
Can confirm 3,4 from above-mentioned table 2, it is very outstanding that the melanin of 5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester generates the inhibition effect.
" test example 3 " to be U373MG Rigen at the neural horn cell of Fructus Rubi corchorifolii Immaturus extract etc. suppress effect according to the IL-6 biosynthesis of P material incentive
Is people's neural horn cell that U373MG is with comprising 10% fetal bovine serum (FBS; Fetalbovine serum) MEM (Minimum Essential Media, GIBCO BRL, LifeTechnologues company) culture medium adheres to 2 * 10 in the lining, each hole (well) of 96-culture vessel (well plate)
4Cultivated 24 hours behind the cells.Get rid of after the culture medium phosphate buffered solution (PBS with 200 μ l; Phosphate Buffered Saline) washs once, and do not containing 5 kinds of extracts that use following table 3 to be put in order in the 200 μ lMEM culture medium of FBS.Get the culture fluid of 25 μ l and measure the free effect that suppresses according to the IL-6 of Substance P by IL-6ELISA (Pharmingen company uses OptEIA Human IL-6/IL-8set).The IL-6 biosynthesis suppression ratio of following table 3 is as criterion calculation the difference of the IL-6 growing amount of the U373 cell of the U373 cell of the P material that is untreated and processing P material.
[table 3]
| Composition | Extract concentrations | IL-6(pg/10 5cells) | IL-6 biosynthesis suppression ratio (%) |
| (-) P material (1M) | - | 10.5±32 | - |
| (+) P material (1M) | - | 981.4±61 | - |
| (+) P material (1M)+stirrup is from extract | 0.01％ | 505.7±41 | 49.0 |
| (+) P material (1M)+blue berry extract | 0.01％ | 582.5±65 | 41.1 |
| (+) P material (1M)+blackberry extract | 0.01％ | 697.4±53 | 29.3 |
| (+) P material (1M)+cranberry extract | 0.01％ | 658.9±38 | 33.2 |
| (+) P material (1M)+Fructus Fragariae Ananssae extract | 0.01％ | 738.1±45 | 25.1 |
*(+): P material (Substance P) is handled, and (-): P material (Substance P) is untreated
Can confirm the Fructus Rubi corchorifolii Immaturus extract from above-mentioned table 3, the blue berry extract, the blackberry extract, cranberry extract, it is very outstanding that Fructus Fragariae Ananssae extract etc. have the biosynthetic effect, especially the Fructus Rubi corchorifolii Immaturus extract that suppress the IL-6 that the P material causes and a blue berry extract in people's neural horn cell U373 IL-6 biosynthesis suppresses effect.
The IL-6 that " test example 4 " Fructus Rubi corchorifolii Immaturus extract etc. stimulate according to Kallidin I skin fiber archeocyte Rigen, the biosynthetic inhibition effect of IL-8
To separate in people's the epidermal tissue, cultured skin fibroblast (Fibroblast) is with the DMEM (Dulbecco ' s Modified Eagle ' s Media that comprises 10% FBS, GIBCO BRL, LifeTechnologues company) culture medium adheres to 2 * 10 on each hole (well) of 96-culture vessel (well plate)
4Cultivated 24 hours behind the cells.After cell culture is about 24 hours, handle the extract that in test example 3, uses with the DMEM that does not put into FBS, cultivate and get culture fluid is carried out IL-6 and IL-8 to each 25 μ l culture fluid ELISA after five hours with the DMEM that contains 1% fetal bovine serum.Begin to estimate IL-6 according to Kallidin I from this experiment, the biosynthesis of IL-8 hinders usefulness.Tabulate down 4 IL-6, the biosynthesis of IL-8 hinder usefulness be the skin fiber archeocyte of the Kallidin I that is untreated and handle the IL-6 of skin fiber archeocyte of Kallidin I or the difference of IL-8 growing amount as criterion calculation.
[table 4]
| Composition | Extract concentrations | IL-6 (pg/10 5cells) | The IL-6 biosynthesis hinders usefulness (%) | IL-8 (pg/10 5cells) | The IL-8 biosynthesis hinders usefulness (%) |
| (-) Kallidin I | - | 0.86±0.27 | - | 2.93±0.99 | - |
| (+) Kallidin I | - | 2.63±0.32 | - | 6.71±1.37 | - |
| (+) Kallidin I+Fructus Rubi corchorifolii Immaturus extract | 0.01％ | 1.57±0.13 | 59.9 | 5.62±0.07 | 28.8 |
| (+) Kallidin I+blue berry extract | 0.01％ | 1.46±0.05 | 66.1 | 5.23±0.38 | 39.2 |
| (+) Kallidin I+blackberry extract | 0.01％ | 1.62±0.18 | 57.1 | 5.92±0.26 | 20.9 |
| (+) Kallidin I+cranberry extract | 0.01％ | 1.70±0.10 | 52.5 | 5.87±0.48 | 22.2 |
| (+) Kallidin I+Fructus Fragariae Ananssae extract | 0.01％ | 1.68±0.25 | 53.7 | 5.80±0.19 | 24.1 |
*(+): Kallidin I (Bradykinin) is handled, and (-): Kallidin I (Bradykinin) is untreated
Can confirm the Fructus Rubi corchorifolii Immaturus extract from above-mentioned table 4, the blue berry extract, the blackberry extract, cranberry extract, Fructus Fragariae Ananssae extract etc. have inhibition in the skin fiber archeocyte to suppress effect according to the IL-6 of biosynthetic effect, especially the Fructus Rubi corchorifolii Immaturus extract of the IL-6 and the IL-8 of Kallidin I and blue berry extract and IL-8 biosynthesis very outstanding.
" test example 5 " suppresses effect the keratinocyte Rigen of Fructus Rubi corchorifolii Immaturus extract etc. according to the prostaglandin biosynthesis that ultraviolet stimulates
Isolating keratinocyte in people's epidermal tissue is put into 5 * 10 in the lining, each hole (well) of 24-culture vessel (well plate)
4Cultivated 24 hours behind the cells.For ultimate density becomes 500mM, in the activity of eliminating the prostaglandin biosynthetic enzyme (Prostaglandin H2synthetase, the perhaps following COX of Cyclooxygenase) that exists in the keratinocyte in the above-mentioned keratinocyte with aspirin (Aspirin) processing.After two hours the PBS washed twice is used in each hole (well) that keratinocyte is housed with the aspirin processing, the PBS of 100 μ l is put in lining, each hole (well) then.Utilize UV-B lamp (F15T8, UVB15W, Sankyo Dennki company, Japan), irradiation ultraviolet radiation 30mJ/cm on these keratinocytes
2, take out PBS then and add 250 μ l keratinocyte culture fluid (Keratinocyte growth media, Clonetics, BioWhittacker company, MD, the U.S.) in lining, each hole (well).After this natural extract that will estimate is handled by the concentration of table 5 arrangement, cultivated 16～20 hours.Through after the certain hour, suitably take out the culture fluid upper strata and quantitatively through 16～20 hours biosynthetic PGE2s (PGE2), and judge the inhibition effect of natural extract prostaglandin.The amount of PGE2 is to utilize enzyme immunoassay (Enzyme immunoassay) quantitative.5 the prostaglandin biosynthesis suppression ratio of tabulating down is that the difference of PGE2 growing amount of keratinocyte of the keratinocyte of not irradiation ultraviolet radiation and irradiation is as criterion calculation.
[table 5]
| Composition | Extract concentrations | PGE2(pg/10 5cells) | Prostaglandin biosynthesis suppression ratio |
| (-)UV B | - | 37.5±8.5 | - |
| (+)UV B | - | 287.4±18.6 | - |
| (+) UV B+ Fructus Rubi corchorifolii Immaturus extract | 0.01％ | 84.7±15.2 | 81.1 |
| (+) UV B+ blue berry extract | 0.01％ | 105.1±20.7 | 72.9 |
| (+) UV B+ blackberry extract | 0.01％ | 114.9±27.3 | 69.0 |
| (+) UV B+ cranberry extract | 0.01％ | 121.6±21.9 | 66.3 |
| (+) UV B+ Fructus Fragariae Ananssae extract | 0.01％ | 118.8±31.1 | 67.5 |
* (+): UVB irradiation, (-): UVB does not shine
From the result of above-mentioned table 5 Fructus Rubi corchorifolii Immaturus extract as can be known, the blue berry extract, the blackberry extract, cranberry extract, Fructus Fragariae Ananssae extract etc. effectively suppress the generation according to ultraviolet prostaglandin in low-down concentration, especially prostaglandin is mainly according to the manufacturing of COX-2 enzyme, so above natural extract suppresses the inducing action or the activity of COX-2 enzyme.
" test example 6 " is to the whitening effect test of human body skin
12 healthy men are adhered to the opaque adhesive plaster with diameter 1.5cm hole as object on tester's upper arm position, shine each tester's minimal erythema dose (MED then; Minimumerythma dose) UV-B about 1.5～2 times and induce the melanism of skin.Behind the irradiation ultraviolet radiation, a part as four kinds of lightening compositions of following table 6 use the solvent 1,3 butylene glycol respectively: ethanol=7: 3 was coated with for 8 weeks with 1% concentration and the parts be left are not coated with anything.With a week is that unit measures with chromatograph (Chromameter) CR2002 (Japan, Minolta company), estimates and be not coated with the poor of " L " value partly,, estimates increase degree (Δ L) that is.And, for relatively, also be coated with 1% the kojic acid (Kojic acid) and the test of excipient (Vehicle) simultaneously.Its result is as shown in table 7 below.
[table 6]
| Active component | Lightening compositions 1 | Lightening compositions 2 | Lightening compositions 3 | Lightening compositions 4 |
| 3,4,5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester | 5.0 | 5.0 | 5.0 | 5.0 |
| The Fructus Rubi corchorifolii Immaturus extract | 50.0 | - | - | 20.0 |
| The blue berry extract | - | 50.0 | - | 20.0 |
| The blackberry extract | - | - | 50.0 | 15.0 |
| Yeast extract | 45.0 | - | - | 15.0 |
| Semen Pisi sativi extract | - | 45.0 | - | 15.0 |
| The kayasenegalensis extract | - | - | 45.0 | 10.0 |
[table 7]
| Substances | Skin-color brightness (Δ L) |
| Excipient (Vehicle) | 0.50±0.15 |
| Kojic acid | 0.99±0.11 |
| Lightening compositions 1 | 1.61±0.25 |
| Lightening compositions 2 | 1.57±0.13 |
| Lightening compositions 3 | 1.39±0.11 |
| Lightening compositions 4 | 1.78±0.18 |
Can confirm that lightening compositions 1～4 obviously has the increase of the L-value that embodies skin-color brightness than the kojic acid of in the past whitening composition and very outstanding from above-mentioned table 7 to the whitening effect of skin.
" dosage form example 1～5 and comparison dosage form example 1 "
In order to estimate the clinical whitening effect of the dosage form that contains The compounds of this invention, by implementing dosage formization as following table 8 usefulness skin preparations for extenal use.At first raw material A, B and C group respectively quantitatively after, in the B group, slowly add the A group and utilize homogenizer (Homogenizer) to carry out softening first time, slowly add the C group again and implement the softening second time, stir then and cool off and obtain final dosage form.
" the test example 7 " clinical effectiveness of whitening
On the face just like the pigment of nevus and 70 of worried testers as object, will contain the dosage form example 1～5 of lightening compositions of the present invention and contain the typical whitening agent of extensively knowing--each was coated in the position that nevus is arranged of face in one time three months to the comparison dosage form example 1 of-kojic acid sooner or later.And, organize the dosage form that does not contain any active component of whitening in contrast and also estimate.
[table 8]
" evaluation methodology "
Use the later pigment of above-mentioned dosage form to improve degree according to following standard determination, the average result of the decision content of 10 user is illustrated in down 9 li of tabulations.
Effect brilliance (3): almost can't see pigment.
(2) produce effect: pigment is very light.
Some effects (1) are arranged: pigment is lighter.
To no effect (0): do not have any variation.
[table 9]
| Substances | Whitening effect is judged meansigma methods |
| Matched group | 0.4±0.12 |
| Compare dosage form example 1 | 1.2±0.21 |
| Dosage form example 1 | 1.8±0.22 |
| Dosage form example 2 | 2.3±0.10 |
| Dosage form example 3 | 2.3±0.38 |
| Dosage form example 4 | 2.1±0.14 |
| Dosage form example 5 | 2.6±0.23 |
Can confirm from above-mentioned table 9, the skin preparations for extenal use that contains The compounds of this invention, include only 3,4, the dosage form of 5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester also embodies more outstanding whitening effect than the dosage form that contains kojic acid, contains the composition of inhibition skin irritation identical with dosage form example 5 or inflammation especially together and promotes the dosage form of heat shock protein synthetic ingredient to have classic whitening effect.
" test example 8 " human body skin hypersensitive test
Up to the present skin irritation not being had the empirical mean age of irritated reaction is that 30 of 25.3 years old health female and male are as object, according to CTFA Guideline (The Cosmetic, Toiletry andFragrance Association, Inc.Washington, D.C.20036,1991) human body skin is carried out following irritant test as object.At first, be contained in the substances that contains 1 weight % compositions 1～4 respectively 20 μ l that press the basic prescriptions that tabulation 10 forms in the Finn chamber after, attached on test position forearm (forearm) skin and fix with little adhesive tape.Carried out skin anaphylactic test in 24 hours, get rid of Finn chamber and use marking pen (marking pen) expression test position later on, the position is respectively tested in one hour and later observation in 24 hours.Press the reaction of tabulation 11 evaluating skins, its result is illustrated in down in the tabulation 12.
[table 10]
[table 11]
| Grade | Mark | Criterion |
| 0 1 2 3 4 | - ± + ++ +++ | Non-stimulated (No visible reactions) weak to stimulate (Mild erythema) strong stimulation (Intense erythema) with the strong stimulation (Intense erythema with edema) of the edema strong stimulation (Intense erythema with edema﹠vesicle) with blister, edema |
[table 12]
[mathematical formulae 1]
The average response degree that obtains according to mathematical formulae 1 is also in table 12 li expression.From above-mentioned table 12 as can be seen, the average response degree value that skin-whitening of the present invention carries out human body irritant test result with preparation composition for external use all is shown as 0～0.83 and non-stimulated 1 littler than being judged to be usually, so can become the compositions to human body safety.
Industrial applicability
As mentioned above; heat shock protein of the present invention generates and promotes composition can respond such as ultraviolet ray or the external pressure such as hot and effective Cell protection; but and not only establishment melanin generation of lightening compositions of the present invention; and can suppress or relax skin irritatin or inflammation; further having increases from the synthetic effect of the heat shock protein of various external pressure Cell protections; the Dermatologic preparation composition that contains these compositions can improve the pigmentation of skin; embody outstanding whitening effect; skin without any stimulation, therefore be can be used as the skin-whitening external preparation and uses.
Claims (4)
1. skin-whitening preparation composition for external use, it is characterized by: it comprises that heat shock protein generates the promotion composition, following Chemical formula 1 represent 3,4,5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester, and the composition that suppresses skin irritation or inflammation, the composition of described inhibition skin irritation or inflammation comprises and being selected from by the Fructus Rubi corchorifolii Immaturus extract, the blue berry extract, cranberry extract, one or more components in the group that blackberry extract and Fructus Fragariae Ananssae extract are formed, described heat shock protein generates and promotes composition to comprise to be selected from by Yi Keduoyin, the Salix alba extract, yeast extract, Semen Pisi sativi extract, the cailcedra bark extract, one or more components in the group that caffeic acid and p-coumaric acid are formed
Chemical formula 1
2. skin-whitening preparation composition for external use as claimed in claim 1, it is characterized by: the described preparation composition for external use of relative 100 weight %, described preparation composition for external use comprises 3 of 0.0001～5 weight %, 4,5-trimethoxy cinnamic acid Herba thymi vulgaris phenolic ester, 0.0001 generating, the heat shock protein of the inhibition skin irritation of～30 weight % or the composition of inflammation and 0.0001～20 weight % promotes composition.
3. skin-whitening preparation composition for external use as claimed in claim 1 is characterized by: described preparation composition for external use is liquor, unguentum, powder agent or facial film.
4. skin-whitening preparation composition for external use as claimed in claim 1 is characterized by: described preparation composition for external use is a skin care liquid, ointment, gelinite, vanishing cream, the percutaneous dosage form of muffin or spray form.
Applications Claiming Priority (3)
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| KR10-2002-0080368 | 2002-12-16 | ||
| KR10-2002-0080368A KR100507293B1 (en) | 2002-12-16 | 2002-12-16 | Component accelerating formation of heat shock protein and composition for external application to the skin with whitening effect containing thereof |
| KR1020020080368 | 2002-12-16 |
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| CN100389743C true CN100389743C (en) | 2008-05-28 |
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Cited By (1)
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| EP4285889A3 (en) * | 2022-05-10 | 2024-03-20 | Amorepacific Corporation | A composition for use in suppressing skin irritation or suppressing sebum secretion |
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| JP4160964B2 (en) * | 2005-04-01 | 2008-10-08 | 株式会社ファンケル | Sweet pea extract-containing cosmetics |
| US8080265B2 (en) * | 2009-02-20 | 2011-12-20 | Johnson & Johnson Consumer Companies, Inc. | Compositions and methods for treating signs of skin aging |
| CN105707469A (en) * | 2016-03-04 | 2016-06-29 | 湖南晶天科技实业有限公司 | Thymol ester, feed additive and feed |
| CN108261379B (en) * | 2018-04-26 | 2020-11-20 | 合肥中科华燕生物技术有限公司 | Facial mask and preparation method thereof |
| CN112007036B (en) * | 2019-05-29 | 2022-01-21 | 百岳特生物科技（上海）有限公司 | Application of compound and composition thereof in preparing medicine for relieving lung epithelial cell inflammation |
| CN110964066B (en) * | 2019-12-26 | 2020-12-01 | 上海澄穆生物科技有限公司 | Salidroside derivative, preparation method and application thereof in whitening cosmetics |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1195285A (en) * | 1995-07-07 | 1998-10-07 | C3D公司 | Depigmenting cosmetic skin-care composition and use thereof |
| CN1203525A (en) * | 1995-11-06 | 1998-12-30 | 普罗克特和甘保尔公司 | Topical compositions for regulating oily/shiny appearance of skin |
| CN1261268A (en) * | 1997-08-01 | 2000-07-26 | 朗开斯特集团有限公司 | Shellac-containing cosmetic product |
| JP2001151633A (en) * | 1999-11-26 | 2001-06-05 | Noevir Co Ltd | Preparation for external use for skin |
| JP2001151631A (en) * | 1999-11-22 | 2001-06-05 | Noevir Co Ltd | Preparation for external use for skin |
| JP2001261570A (en) * | 2000-03-22 | 2001-09-26 | Nisshin Oil Mills Ltd:The | Skin care preparation |
-
2002
- 2002-12-16 KR KR10-2002-0080368A patent/KR100507293B1/en active IP Right Grant
-
2003
- 2003-12-16 CN CNB200310118463XA patent/CN100389743C/en not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1195285A (en) * | 1995-07-07 | 1998-10-07 | C3D公司 | Depigmenting cosmetic skin-care composition and use thereof |
| CN1203525A (en) * | 1995-11-06 | 1998-12-30 | 普罗克特和甘保尔公司 | Topical compositions for regulating oily/shiny appearance of skin |
| CN1261268A (en) * | 1997-08-01 | 2000-07-26 | 朗开斯特集团有限公司 | Shellac-containing cosmetic product |
| JP2001151631A (en) * | 1999-11-22 | 2001-06-05 | Noevir Co Ltd | Preparation for external use for skin |
| JP2001151633A (en) * | 1999-11-26 | 2001-06-05 | Noevir Co Ltd | Preparation for external use for skin |
| JP2001261570A (en) * | 2000-03-22 | 2001-09-26 | Nisshin Oil Mills Ltd:The | Skin care preparation |
Non-Patent Citations (4)
| Title |
|---|
| 植物的应激反应和应激蛋白. 王三根.生命的化学，第15卷第1期. 1995 |
| 植物的应激反应和应激蛋白. 王三根.生命的化学，第15卷第1期. 1995 * |
| 豌豆中可与Gro EL抗体发生免疫学反应的热激诱导蛋白. 陈忠等.植物学报，第40卷第10期. 1998 |
| 豌豆中可与Gro EL抗体发生免疫学反应的热激诱导蛋白. 陈忠等.植物学报，第40卷第10期. 1998 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4285889A3 (en) * | 2022-05-10 | 2024-03-20 | Amorepacific Corporation | A composition for use in suppressing skin irritation or suppressing sebum secretion |
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| KR20040053907A (en) | 2004-06-25 |
| CN1520804A (en) | 2004-08-18 |
| KR100507293B1 (en) | 2005-08-09 |
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