CN109789081A - The method of skin lightening compositions comprising TNFRSF14 inhibiting substances and screening TNFRSF14 inhibiting substances - Google Patents
The method of skin lightening compositions comprising TNFRSF14 inhibiting substances and screening TNFRSF14 inhibiting substances Download PDFInfo
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Abstract
The invention discloses the methods of the expression of composition for whitening skin and screening TNFRSF14 or activity inhibitor matter comprising TNFRSF14 expression or activity inhibitor matter as active constituent.Composition comprising TNFRSF14 expression or activity inhibitor matter as active constituent can reduce the melanin content in skin, to provide excellent whitening effect.It, can easily screening skin-whitening substance by confirming relative expression's inhibition level of TNFRSF14 gene also, according to the screening method.
Description
Technical field
The present invention relates to composition for whitening skin and for the method for screening skin-whitening substance.
Background technique
The melanin that the effect of the various enzymes such as tyrosinase generates in melanocyte in human body is to determine human skin color
Most important factor will induce such as chloasma, freckle and mole pigmentation when it is excessively more than to need that melanin, which generates,
Disease is cosmetically bringing undesirable consequence.Also, because the melanin that the stress stimulation in the inside and outside portion of skin generates is passing through skin
Skin keratinization discharge before, will not with stress disappearance and disappear.
Therefore, carrying out inhibiting the research of this melanin production, and in cosmetics and drug with the use of anti-
Bad hematic acid, kojic acid, arbutin, quinhydrones, glutathione or derivatives thereof or the substance inhibited tyrosinase activity.But due to
Insufficient whitening effect of these substances and safety problem to skin, cause their use to be restricted.
[related fields bibliography]
[patent document]
(patent document 1) Korean Patent Publication No. 10-2013-0025768 (2013.03.12)
Summary of the invention
Technical problem
In one aspect, the object of the present invention is to provide a kind of for adjusting the novel skin of the B16 cell in skin
Whitening material identifies marker.
On the other hand, the object of the present invention is to provide a kind of composition for whitening skin, the composition includes
The expression for being used to that the skin-whitening substance to be inhibited to identify marker or active substance as active constituent.
On the other hand, carry out screening skin using skin-whitening substance identification marker the object of the present invention is to provide a kind of
The method of skin whitening material..
On the other hand, the object of the present invention is to provide one kind identifies marker by using the skin-whitening substance to examine
The compositions or agents box of the relevant skin condition of off-color element.
On the other hand, the object of the present invention is to provide one kind identifies marker by using the skin-whitening substance to examine
The essential information providing method of the relevant skin condition of off-color element.
Technical solution
On the one hand, the present invention provides a kind of composition for whitening skin, and the composition includes as active constituent
For inhibit TNFRSF14 (TNF receptor superfamily member 14) expression or active substance.
On the one hand, the present invention provides a kind of screening method of skin-whitening substance, includes the following steps:
(a) test substances are handled to melanocyte；With
(b) confirm whether the test substances inhibit TNFRSF14 in melanocyte (TNF receptor superfamily member 14)
Expression.
On the one hand, the present invention is provided to diagnose the composition of the relevant skin condition of pigment, the composition includes to be used for
Detect the reagent of the mRNA or TNFRSF14 protein of TNFRSF14.
On the one hand, the present invention is provided to diagnose the kit of the relevant skin condition of pigment, which includes to be used for
Detect the reagent of the mRNA or TNFRSF14 protein of TNFRSF14.
On the one hand, the present invention is provided to diagnose the method for the essential information of the relevant skin condition of pigment offer, the party
Method includes the mRNA or protein expression level that TNFRSF14 is confirmed from the Skin Cell that subject separates.
Beneficial effect
Novel skin whitening material according to an aspect of the present invention, which identifies marker TNFRSF14, to be reduced in skin
The synthesis of melanin.Therefore, comprising as active constituent for inhibit the TNFRSF14 expression or active substance
Composition is effectively used for skin-whitening.In addition, according to an aspect of the present invention, skin-whitening substance screening method is to pass through
Test substances are handled in skin to and are confirmed relative expression's inhibition level of TNFRSF14 gene, to be easy, effectively identify skin
Skin whitening material.The according to an aspect of the present invention compositions or agents box for diagnosing the relevant skin condition of pigment, with
And the essential information providing method for diagnosing the relevant skin condition of pigment, it can be by the TNFRSF14 for including in skin
Gene is detected, and quickly and easily to diagnose the relevant skin condition of pigment, or can provide relevant rudimentary information.
Detailed description of the invention
Fig. 1 is to compare figure according to the relative amount of melanin in the melanocyte of TNFRSF14 gene expression inhibition degree.
Specific embodiment
Hereinafter, the present invention is described in detail.
In the present specification, term " skin " refers to the organ outside covering organism, by epidermis, corium and subcutaneous rouge
Fat layer composition, being not only includes the tissue covered outside entire face or body, further includes the broadest general of scalp and hair
It reads.
One embodiment of the present of invention can provide for skin-whitening method comprising to needing the object of skin-whitening to apply
With for inhibiting the expression of TNFRSF14 or the step of active substance.
Another embodiment can provide composition for whitening skin, and it includes be used to inhibit as active constituent
The expression of TNFRSF14 or active substance.
Another embodiment can provide expression for inhibiting TNFRSF14 or active substance in preparation for skin
Purposes in the composition of whitening.
In addition, another embodiment can provide the expression or active inhibiting substances of the TNFRSF14 for skin-whitening.
In one embodiment of the invention, the expression for inhibiting TNFRSF14 or active substance can be use
In the substance for inhibiting TNFRSF14 mRNA translation, at least partly combined more specifically, may include with TNFRSF14 mRNA
Oligonucleotides.
Although whether the TNFRSF14 and B16 cell have relationship also unclear, the present inventor passes through
The study found that in the adjustable melanocyte in skin of TNFRSF14 melanin synthesis.More specifically, it has already been proven that work as skin
When the expression of TNFRSF14 described in the melanocyte of skin or activity inhibited or reduction, melanin generates quantitative change and reduces.
In one embodiment of the invention, the oligonucleotides can be any one in siRNA, shRNA and miRNA
Kind is a variety of.The expression for inhibiting TNFRSF14 or active substance can interfere (RNAi) phenomenon to can induce RNA
SiRNA, shRNA and miRNA in any one or more.One embodiment of the present of invention can be by can induce
The RNAi phenomenon of TNFRSF14mRNA interference inhibits the mRNA of TNFRSF14 gene to express.
MiRNA is a kind of tiny RNA (endogenous tiny RNA) being present in cell, derives from and does not synthesize protein
DNA is generated by hairpin transcript (hairpin-shaped transcript).Pass through the 3'-UTR's of miRNA and said target mrna
Complementary series combines, and to inhibit translation or the induction stabilization removal of mRNA, inhibits the egg of said target mrna eventually as inhibiting factor
White matter synthesis.It is known that a miRNA targets several mRNA, and mRNA can also be by the adjusting of several miRNA.Induce RNAi phenomenon
Other RNA have the short interfering rna (siRNA) of the short rna as 19-27mer, and there is short hair clip (short hairpin)
The shRNA of structure.
In one embodiment of the invention, the oligonucleotides is double-strand, specifically, can for siRNA, shRNA or
Any one in miRNA, and include nucleotide sequence shown in SEQ ID NO:1 and with the interfertile core of SEQ ID NO:1
Nucleotide sequence.
5'-GUGUGGUGUUUAGUGGAUA-3'(SEQ ID NO:1)
In one embodiment, the oligonucleotides is double-strand, specifically, can be in siRNA, shRNA and miRNA
It is any, and include nucleotide sequence shown in SEQ ID NO:1 and SEQ ID NO:2, and can be by SEQ ID NO:1 and SEQ
Nucleotide sequence shown in ID NO:2 is through hybridizing.
Justice: 5'-GUGUGGUGUUUAGUGGAUA-3'(SEQ ID NO:1)
Antisense: 5'-UAUCCACUAAACACCACAC-3'(SEQ ID NO:2)
In one embodiment, the oligonucleotides is double-strand, specifically, can be in siRNA, shRNA or miRNA
It is any, and include nucleotide sequence shown in SEQ ID NO:3 and with the interfertile nucleotide sequence of SEQ ID NO:3.
5'-CAGGUUAUCGUGUGAAGGA-3'(SEQ ID NO:3)
In one embodiment, the oligonucleotides is double-strand, specifically, can be in siRNA, shRNA and miRNA
It is any, and include nucleotide sequence shown in SEQ ID NO:3 and SEQ ID NO:4, and can be by SEQ ID NO:3 and SEQ
Nucleotide sequence shown in ID NO:4 is through hybridizing.
Justice: 5'-CAGGUUAUCGUGUGAAGGA-3'(SEQ ID NO:3)
Antisense: 5'-UCCUUCACACGAUAACCUG-3'(SEQ ID NO:4)
The oligonucleotides according to an embodiment of the invention can be trapped in liposome or be inserted in carrier
Form be included.
In one embodiment, the concentration of the oligonucleotides can be 1-200nM.More specifically, the oligonucleotides
Concentration can be 5-50nM.
The concentration of the oligonucleotides can for 1nM or more than, 2nM or more than, 3nM or more than, 5nM or more than, 7nM or with
Upper, 9nM or more than, 11nM or more than, 15nM or more than, 16nM or more than, 17nM or more than, 18nM or more than, 19nM or more than,
20nM or more than, 21nM or more than, 22nM or more than, 23nM or more than, 24nM or more than, 25nM or more than or 50nM or more.
In addition, the concentration of the oligonucleotides can be 200nM or following, 190nM or following, 180nM or following, 170nM
Or following, 150nM or following, 130nM or following, 100nM or following, 80nM or following, 50nM or following, 40nM or following,
30nM or following, 29nM or following, 28nM or following, 27nM or following, 26nM or following, 25nM or following, 24nM or following,
23nM or following, 22nM or following, 21nM or following, 20nM or following, 19nM or following, 18nM or following, 17nM or following,
16nM or following, 15nM or following, 14nM or following, 13nM or following, 12nM or following, 11nM or following or 10nM or following.
The concentration of the oligonucleotides within the above range when, the expression inhibiting excellent effect of TNFRSF14, and being suitble to
For skin-whitening.
In one embodiment, the mRNA sequence of the TNFRSF14 (TNF receptor superfamily member 14) is NCBI reference
Sequence NM_003820.3 (NCBI Reference Sequence NM_003820.3), more specifically, can be expressed as following
The nucleotide sequence of SEQ ID NO:5.
(http://www.ncbi.nlm.nih.gov/nuccore/NM_003820.3? report=GenBank)
The composition according to an embodiment of the invention may include the 0.00001-30 weight for accounting for composition total weight
The expression for inhibiting TNFRSF14 of amount % or active substance.
In addition, the composition according to an embodiment of the invention can be Dermatologic preparation composition, more specifically
Ground may include cosmetic composition or pharmaceutical composition.
In one embodiment, the cosmetic composition can provide as all formulations suitable for part.For example, can mention
For being mutually dispersed in the lotion obtained in water phase for solution, by oil, the lotion for obtaining Aqueous dispersions in oily phase, suspension, consolidating
The dosage form of body, gel, powder, paste, foam or aerosol composition.Such preparation can be prepared according to the conventional method of this field
Composition.
In one embodiment, the cosmetic composition in addition to the foregoing, in the model for not damaging main effect
In enclosing, it is preferable that can also include the other compositions that can generate synergistic effect with main effect.Cosmetics according to the present invention
Composition may include the substance in vitamin, macromolecule peptide, macromolecule polysaccharide and sphingolipid.In addition, in one embodiment
In, the cosmetic composition may include moisturizer, lubricant, interfacial agent, ultraviolet absorbing agent, preservative, fungicide,
Antioxidant, pH adjusting agent, organic and inorganic pigment, fragrance, coolant, antiperspirant.Those skilled in the art can not damage
The content of mentioned component is readily selected in the range of evil the object of the invention and effect, which can account for composition total weight
0.01-5 weight % specifically can account for 0.01-3 weight %.
In addition, in one embodiment, described pharmaceutical composition can provide as all formulations suitable for part.For example,
It can be administered by oral, transdermal, vein, muscle, subcutaneous injection.In one embodiment, described pharmaceutical composition can be
Injection, externally used liquid for skin, suspension, lotion, gel, patch or spray, but not limited to this.The preparation can be according to this
The conventional method in field is easily prepared, and interfacial agent can be suitably used, excipient, wetting agent, emulsification promoter, hang
Floating agent, the salt for controlling osmotic pressure or buffer, colorant, fragrance, stabilizer, preservative, preservative agent or it is other commonly use it is auxiliary
Auxiliary agent.
Age of the effective component of pharmaceutical composition according to an embodiment of the invention according to object, gender, weight, disease
The judgement of reason situation and severity, administration route or prescriber and change.According to these because usually determining dosage in this field
In the level of those of ordinary skill, for example, its daily dose can be -5000mg/kg/ days 0.1mg/kg/ days, more specifically,
It can be -500mg/kg/ days 50mg/kg/ days, but not limited to this.
Another embodiment of the invention can provide the side of the screening skin-whitening substance by using the TNFRSF14
Method.
In one embodiment, it the described method comprises the following steps: test substances processing (a) being carried out to melanocyte；With
And (b) whether exact p-value substance inhibits the expression of TNFRSF14 in melanocyte.Here, in the step (b) whether suppression
The expression of TNFRSF14 processed can be whether to inhibit the translation of TNFRSF14 mRNA.
In one embodiment, the step (b) may include before and after handling melanocyte test substances
The step of relative expression's inhibition level of FRSF14 confirms.In addition, the step (b) may include to through handling test substances
Melanocyte and relative expression's inhibition levels of melanocyte of untreated test substances the step of confirming.
In addition, one embodiment may further include: by the determination of the step (b) as a result, working as the tester
When matter inhibits the expression of TNFRSF14, the step of test substances are skin-whitening substance is determined.
In this specification, term " relative expression's inhibition level " can be in the melanocyte before handling test substances
The expression of TNFRSF14 is compared with the expression for handling the TNFRSF14 in the melanocyte after test substances, table
Up to repressed degree.Alternatively, " relative expression's inhibition level " can be the TNFRSF14 of the melanocyte through handling test substances
Expression compared with the expression of the TNFRSF14 of the melanocyte of untreated test substances when expression pressed down
The degree of system.The expression may include expression quantity and expression quality.In addition, expression is for example, it may include protein
Expression.More specifically, the expression may include the degree of the B16 cell in melanocyte.
In one embodiment of the present of invention, the step of being determined as the skin-whitening substance can include: when " relative expression's suppression
When processing procedure degree " is twice or twice or more, then it is determined as skin-whitening substance.That is, the melanocyte before processing test substances is thin
The expression phase of the expression of TNFRSF14 in born of the same parents and the TNFRSF14 in the melanocyte after processing test substances
Than can determine that as skin-whitening substance when expression is suppressed about 1.1-2 times or more.Alternatively, when through processing test substances
The expression phase of the expression of TNFRSF14 and TNFRSF14 in the melanocyte of untreated test substances in melanocyte
Than can determine that as skin-whitening substance when expression is suppressed about 1.1-2 times or more.
For example, the relative expression of the TNFRSF14 presses down after processing test substances compared with before processing test substances
Processing procedure degree can be 1.1 times or more, 1.2 times or more, 1.3 times or more, 1.4 times or more, 1.5 times or more, 1.6 times
Or above, 1.7 times or more, 1.8 times or more, 1.9 times or more or 2 times or more, but not limited to this.The expression water
Flat is the result measured in the case where ensuring statistical significance.The concept of statistical significance includes being analyzed by biometric
The case where significant difference that method is shown, by situation of the p value less than 0.05 when including quantitative.
In the step of according to one embodiment (a), the test substances can be transfected into the liposome or carrier of cell
In, and cell can be melanocyte, i.e. melanocyte.The transfection can be total by using microinjection, calcium phosphate
The precipitation method, electroporation or liposome are carried out using method etc., but not limited to this.
In addition, in one embodiment, the expression of the TNFRSF14 can be determined using known technology, for example,
RT-PCR method, ELISA method, western blot method or immunoblotting (immune blot) method, but not limited to this.
In addition, one embodiment of the present of invention can provide the biomarker for diagnosing the relevant skin condition degree of pigment
Object.In addition, one embodiment of the present of invention can provide by being used to diagnose the relevant skin of pigment using the biomarker
The composition of skin state, or the kit for diagnosing the relevant skin condition of pigment.Another embodiment of the invention can mention
For the diagnosis side of essential information providing method or the relevant skin condition of pigment for diagnosing the relevant skin condition of pigment
Method.
Specifically, one embodiment of the present of invention can provide mRNA the or TNFRSF14 protein detection comprising TNFRSF14
The composition for being used to diagnose the relevant skin condition of pigment of reagent.
In addition, another embodiment of the invention can provide mRNA the or TNFRSF14 protein detection reagents of TNFRSF14
Preparing the purposes in the composition for diagnosing the relevant skin condition of pigment.
In addition, another embodiment of the invention can provide the TNFRSF14's for diagnosing the relevant skin disorder of pigment
MRNA or TNFRSF14 protein assay reagent.
In addition, another embodiment of the invention can provide, for diagnosing the essential information of the relevant skin condition of pigment
Providing method or method for diagnosing the relevant skin condition of pigment comprising right from the Skin Cell that subject separates
The step of expression quantity of TNFRSF14 is confirmed.At this point, in one embodiment, TNFRSF14 expression quantity can be
The expression quantity of the mRNA or TNFRSF14 protein of TNFRSF14, and the Skin Cell isolated from subject and normal
The Skin Cell of control group can be melanocyte.
In one embodiment, for diagnosing the essential information providing method of the relevant skin condition of pigment or for diagnosing color
The method of the relevant skin condition of element further includes, by the TNFRSF14 expression quantity from the Skin Cell that subject separates and just
The step of TNFRSF14 expression quantity is compared in normal control group Skin Cell.In addition, in one embodiment, the method is also
Including when the TNFRSF14 expression quantity from the Skin Cell that subject separates is higher than normally in group photograph Skin Cell
When TNFRSF14 expression quantity, exist with the relevant skin condition of pigment abnormal come the step of providing information or diagnose.For example, such as
From the TNFRSF14 expression quantity in the Skin Cell that subject separates than in Normal group Skin Cell described in fruit
At about high 1.1-2 times or more of the expression quantity of TNFRSF14, it is abnormal to can determine whether that the relevant skin condition of pigment exists.More specifically
Ground, for example, the expression quantity and Normal group Skin Cell phase from the TNFRSF14 in the Skin Cell that subject separates
Than, high 1.1 times or more, 1.2 times or more, 1.3 times or more, 1.4 times or more, 1.5 times or more, 1.6 times or more,
At 1.7 times or more, 1.8 times or more, 1.9 times or more or 2 times or more, it can determine whether that the relevant skin condition of pigment is deposited
In exception.The expression quantity is the result measured in the case where ensuring statistical significance.The concept of statistical significance includes logical
The case where crossing the significant difference that biology is shown, by situation of the p value less than 0.05 when including quantitative.
In addition, another embodiment of the invention can provide mRNA the or TNFRSF14 protein detection comprising TNFRSF14
The kit for being used to diagnose the relevant skin condition of pigment of reagent, the kit may further include specification, the explanation
Book describes above-mentioned for diagnosing the essential information providing method of the relevant skin condition of pigment, or skin relevant to pigment
The diagnostic method of state.
In addition, in one embodiment, the composition for being used to diagnose the relevant skin condition of pigment, or for diagnosing
The TNFRSF14 mRNA detection reagent for including in the kit of the relevant skin condition of pigment may include and TNFRSF14 is specific
In conjunction with one of primer and probe or a variety of.In one embodiment, the TNFRSF14 protein detection reagents can wrap
Containing one of antibody and probe specifically bound with TNFRSF14 or a variety of.
Hereinafter, composition and effect of the invention is described in more details in reference implementation example.But reality below
It applies example to be only used for helping to understand the present invention, is not intended to limit scope of the invention and range.
[experimental example 1]
By carrying out following experiments, it is identified through the formation for inhibiting the expression of TNFRSF14 to reduce pigment.
Prepare the primary melanocyte of the pigmented people of moderate (moderately pigmented Human primary
Melanocyte) (Thermofisher, https: //www.thermofisher.com/order/catalog/ are purchased from
Product/C1025C? ICID=search-product).
In order to reduce the expression of TNFRSF14 in the melanocyte, introducing shows TNFRSF14 mRNA sequence
Following two TNFRSF14 siRNA of specificity.
Embodiment 1:si-TNFRSF14#1
Justice: 5'-GUGUGGUGUUUAGUGGAUA-3'(SEQ ID NO:1)
Antisense: 5'-UAUCCACUAAACACCACAC-3'(SEQ ID NO:2).
Embodiment 2:si-TNFRSF14#2
Justice: 5'-CAGGUUAUCGUGUGAAGGA-3'(SEQ ID NO:3)
Antisense: 5'-UCCUUCACACGAUAACCUG-3'(SEQ ID NO:4).
Specifically, on the primary melanocyte of the people as melanocyte strain, by the embodiment 1
TNFRSF14siRNA by using liposome transfection to intracellular, up to TNFRSF14 siRNA concentration reaches 20nM.The rouge
Plastid using Lipofectaminer RNAiMAX reagent (Thermo Fisher Scientific, https: //
www.thermofisher.com/order/catalog/product/13778150).The TNFRSF14 of the embodiment 2
SIRNA is transfected into the cell also by method identical with above-described embodiment 1 using liposome (liposome), until
TNFRSF14 sIRNA concentration reaches 20nM.
Using any gene for not reducing the mankind is functionally proved to be, i.e., using cell proliferation and to cell activity
Influence minimum siRNA Silencer Select Negative Control No.1siRNA (Thermo
Fisher Scientific, https: //www.thermofisher.com/order/catalog/product/4390843?
ICID=searc h-product) it is used as negative control group.
By each transfection Examples 1 and 2, negative control group cell at 37 DEG C, 5%CO2About 7 are cultivated in incubator
It.
After each cell is washed twice with PBS buffer solution (5ml), 1ml PBS buffer solution is added, is then scraped with scraper plate
Under all cells, be centrifuged 5 minutes, be made cell granulations (cell pellet) with the speed of 13000rpm, and pass through observation cell
The color of particle come compare pigment formation degree.
As a result as shown in Figure 1, it may be determined that in 1 He of embodiment for the expression for inhibiting TNFRSF14 using TNFRSF14 siRNA
2 with negative control phase group ratio, and the melanin amount contained in melanocyte is significant to reduce about 1.5 times or more.It means that when suppression
In skin processed when the expression or activity of TNFRSF14, skin whitening effects can be shown.
The preparation embodiment of composition according to an embodiment of the invention is described below, can also be applied various in it
His preparation, its object is to the present invention is described in detail, but are not intended to limit the present invention.
[preparation embodiment 1] nutrition toner
According to the conventional method of cosmetic field, according to proportion preparation nutrition toner shown in following [table 1].
[table 1]
[preparation embodiment 2] nutritional emulsions
According to the conventional method of cosmetic field, nutritional emulsions are prepared according to proportion shown in following [table 2].
[table 2]
[preparation embodiment 3] nourishing cream
According to the conventional method of cosmetic field, nourishing cream is prepared according to proportion shown in following [table 3].
[table 3]
[preparation embodiment 4] injection
According to the conventional method of cosmetic field, injection is prepared according to proportion shown in following [table 4].
[table 4]
| Raw material name content | Weight ratio (every 1ml) |
| Sodium chloride | 9.0mg |
| Sodium carboxymethylcellulose | 30.0mg |
| Polysorbas20 | 1.0mg |
| Liposome comprising embodiment 1 or 2 | 1.0mg |
| Distilled water for injection | In right amount |
[preparation embodiment 5] ointment
According to the conventional method of cosmetic field, ointment is prepared according to proportion shown in following [table 5].
<110>Amorepacific Corporation
<120>method of skin lightening compositions and screening TNFRSF14 inhibiting substances comprising TNFRSF14 inhibiting substances
<130> OF17P112PCT
<150> KR 10-2016-0122318
<151> 2016-09-23
<160> 5
<170> KoPatentIn 3.0
<210> 1
<211> 19
<212> RNA
<213> Artificial Sequence
<220>
<223> sense siRNA of TNFRSF14 #1
<400> 1
gugugguguu uaguggaua 19
<210> 2
<211> 19
<212> RNA
<213> Artificial Sequence
<220>
<223> antisense siRNA of TNFRSF14 #1
<400> 2
uauccacuaa acaccacac 19
<210> 3
<211> 19
<212> RNA
<213> Artificial Sequence
<220>
<223> sense siRNA of TNFRSF14 #2
<400> 3
cagguuaucg ugugaagga 19
<210> 4
<211> 19
<212> RNA
<213> Artificial Sequence
<220>
<223> antisense siRNA of TNFRSF14 #2
<400> 4
uccuucacac gauaaccug 19
<210> 5
<211> 3519
<212> RNA
<213> Artificial Sequence
<220>
<223> mRNA of TNFRSF14
<400> 5
tccttcatac cggcccttcc cctcggcttt gcctggacag ctcctgcctc ccgcagggcc 60
cacctgtgtc ccccagcgcc gctccaccca gcaggcctga gcccctctct gctgccagac 120
accccctgct gcccactctc ctgctgctcg ggttctgagg cacagcttgt cacaccgagg 180
cggattctct ttctctttct ctttctcttc tggcccacag ccgcagcaat ggcgctgagt 240
tcctctgctg gagttcatcc tgctagctgg gttcccgagc tgccggtctg agcctgaggc 300
atggagcctc ctggagactg ggggcctcct ccctggagat ccacccccaa aaccgacgtc 360
ttgaggctgg tgctgtatct caccttcctg ggagccccct gctacgcccc agctctgccg 420
tcctgcaagg aggacgagta cccagtgggc tccgagtgct gccccaagtg cagtccaggt 480
tatcgtgtga aggaggcctg cggggagctg acgggcacag tgtgtgaacc ctgccctcca 540
ggcacctaca ttgcccacct caatggccta agcaagtgtc tgcagtgcca aatgtgtgac 600
ccagccatgg gcctgcgcgc gagccggaac tgctccagga cagagaacgc cgtgtgtggc 660
tgcagcccag gccacttctg catcgtccag gacggggacc actgcgccgc gtgccgcgct 720
tacgccacct ccagcccggg ccagagggtg cagaagggag gcaccgagag tcaggacacc 780
ctgtgtcaga actgcccccc ggggaccttc tctcccaatg ggaccctgga ggaatgtcag 840
caccagacca agtgcagctg gctggtgacg aaggccggag ctgggaccag cagctcccac 900
tgggtatggt ggtttctctc agggagcctc gtcatcgtca ttgtttgctc cacagttggc 960
ctaatcatat gtgtgaaaag aagaaagcca aggggtgatg tagtcaaggt gatcgtctcc 1020
gtccagcgga aaagacagga ggcagaaggt gaggccacag tcattgaggc cctgcaggcc 1080
cctccggacg tcaccacggt ggccgtggag gagacaatac cctcattcac ggggaggagc 1140
ccaaaccact gacccacaga ctctgcaccc cgacgccaga gatacctgga gcgacggctg 1200
ctgaaagagg ctgtccacct ggcggaacca ccggagcccg gaggcttggg ggctccgccc 1260
tgggctggct tccgtctcct ccagtggagg gagaggtggg gcccctgctg gggtagagct 1320
ggggacgcca cgtgccattc ccatgggcca gtgagggcct ggggcctctg ttctgctgtg 1380
gcctgagctc cccagagtcc tgaggaggag cgccagttgc ccctcgctca cagaccacac 1440
acccagccct cctgggccag cccagagggc ccttcagacc ccagctgtct gcgcgtctga 1500
ctcttgtggc ctcagcagga caggccccgg gcactgcctc acagccaagg ctggactggg 1560
ttggctgcag tgtggtgttt agtggatacc acatcggaag tgattttcta aattggattt 1620
gaattcggct cctgttttct atttgtcatg aaacagtgta tttggggaga tgctgtggga 1680
ggatgtaaat atcttgtttc tcctcaaact gtcacctccc ggtgtttctt gctgaacaag 1740
gagttccagg atggctgctg ggctgttcgg gggacccctg ccctcctccc gtcatgcctg 1800
ggggttcact ccacccagag aggagccctg gccgcccctt catatcccaa cagctgagct 1860
ctcagtgggc tcttctgacc tctgtggctc cgtccgaggc tattgctgtg gattctgatg 1920
ctcaaatggt gtcagatttg cccagtaaaa accccagatc tacatctgac ctacacttcc 1980
cagctgtgtc caccgagaaa ccccagtatc agtgacgcct gctgtgccca gccctctcca 2040
cctgctccgg gaacccgcca ggcccaggtc ccgctggcag gggcttcacc aggcctctga 2100
gccacacatt catttaatgg tcgggatgag gcccctttcc ccacatctga agttagaagc 2160
ggtgagggga atgaccctgc agccatgcca tgaggatgga ggccacatag cccctccgag 2220
catgcccgct ccaccccgcc ctaccccctc tcctttcctt gtcacctgcc tccagcagag 2280
cccccaggct gagccaccca ccccaactcc tctcctgcca ccccttgtcc tgtggaagct 2340
ttggcttagc gtcctggggt gtggagaggc ccatgcaggc caggtggagc cctgggcccc 2400
tagaaagcag cacttctggc tgccccaccc cgtgtcaccc tctccccaac tggaggcgtg 2460
gtctccaggg accacgggcc tccctgtgca tggaccggct cctgaccacc gtccagggtc 2520
attgccaggg taccttttca gaggctgacc ccatagacct ggctgccccc cagtgctaga 2580
tgggagccaa gcacagcctg cccttctgcc cacagtcccg ggggcaggtg ggagcatggg 2640
gccatggagt gagcgggcag gggtggcaga gggctccctg gtcaggggcc ccaacttccc 2700
ttcccccagg gaggccacct gacatctggg ctccaggcac agcaggaagc ccacctgccc 2760
caacctgtag ctcctcctcc tgggaggagc catggatcct ggaaaagctc tggggccacc 2820
tcccaggttt ggggggacag agctccaaga gacgacggct ggggacacga gccctcatgg 2880
ggccgctgtg tgctcacccc ttgattttct tcttttcatg catgagatta ggccaagtgt 2940
ggagaaatca atgatgttga cgatgaggct ccctgagaga aatcacaccc agcgggagct 3000
gctgctccca ggtctggcct cggtcaccag ccacctgctg catccgcggg agtggggccg 3060
aggacatggg agtggcaggt gcagcccccg gtactcactc agccccaggg agtgtccctg 3120
gctcccaggg ctctgggagg tgagggcagg tcccggggga ggctgggtta gtggcagctc 3180
cgggatgaga cctcagaggt ctgtctgact tgtccaagcc cggctatggg gaggtggggg 3240
gaaggaagga agaggagaga aataaggaga ggctgggcaa agaagacagg acggcagagg 3300
gagaggggag agaagtggga ggcagccagc agcgcagggc cctgagagta tttcagcggc 3360
accgctgtcc tgggccgccc ggtgccacat ctttgaaaac agttgtttaa tttaagcttg 3420
tccactcagt agctgttgaa tgtgggaggt tatcttgttc tattcaagtt gctataaaaa 3480
taaaaactac catagactgg gaaaaaaaaa aaaaaaaaa 3519
Claims (23)
1. a kind of composition for whitening skin, the composition includes as effective component for inhibiting TNFRSF14 (TNF
Receptor superfamily member 14) expression or active substance.
2. composition for whitening skin according to claim 1, which is characterized in that described for inhibiting TNFRSF14
Expression or active substance include substance for inhibiting the translation of TNFRSF14 mRNA.
3. composition for whitening skin according to claim 2, which is characterized in that described for inhibiting TNFRSF14
Expression or active substance include the oligonucleotides that is at least partly combined with TNFRSF14 mRNA.
4. composition for whitening skin according to claim 3, which is characterized in that the oligonucleotides be siRNA,
Any one or more in shRNA or miRNA.
5. composition for whitening skin according to claim 3, which is characterized in that the oligonucleotides be double-strand and
Comprising nucleotide sequence shown in SEQ ID NO:1 and with the interfertile nucleotide sequence of the SEQ ID NO:1.
6. composition for whitening skin according to claim 3, which is characterized in that the oligonucleotides be double-strand and
Comprising nucleotide sequence shown in SEQ ID NO:1 and SEQ ID NO:2, by the SEQ ID NO:1 and SEQ ID NO:2 institute
The nucleotide sequence shown is through hybridizing.
7. composition for whitening skin according to claim 3, which is characterized in that the oligonucleotides be double-strand and
Comprising nucleotide sequence shown in SEQ ID NO:3 and with the interfertile nucleotide sequence of SEQ ID NO:3.
8. composition for whitening skin according to claim 3, which is characterized in that the oligonucleotides be double-strand and
Comprising nucleotide sequence shown in SEQ ID NO:3 and SEQ ID NO:4, by the SEQ ID NO:3 and SEQ ID NO:4 institute
The nucleotide sequence shown is through hybridizing.
9. the composition for whitening skin according to any one of claim 3-8, which is characterized in that widow's core
Thuja acid is to be trapped in liposome or be inserted in the form in carrier and be included.
10. composition for whitening skin according to claim 1, which is characterized in that the composition is cosmetics
Composition.
11. composition for whitening skin according to claim 1, which is characterized in that the composition is medicine group
Close object.
12. composition for whitening skin according to claim 1, which is characterized in that the composition includes to account for institute
State the 0.00001-30 weight % of composition total weight for inhibit TNFRSF14 expression or active substance.
13. a kind of screening method of skin-whitening substance, includes the following steps:
(a) test substances are handled to melanocyte；With
(b) confirm whether the test substances inhibit the table of the NFRSF14 (TNF receptor superfamily member 14) in melanocyte
It reaches.
14. the screening method of skin-whitening substance according to claim 14, which is characterized in that in the step (b)
Whether inhibit the expression of TNFRSF14 refers to the translation for whether inhibiting TNFRSF14 mRNA.
15. the screening method of skin-whitening substance according to claim 13, which is characterized in that the step (b) includes
The step of relative expression's inhibition level of FRSF14 before and after handling test substances to melanocyte confirms.
16. the screening method of skin-whitening substance according to claim 13, which is characterized in that the step (b) includes
Relative expression's inhibition level of the melanocyte of melanocyte and untreated test substances through handling test substances is carried out true
The step of recognizing.
17. the method for screening skin-whitening substance according to claim 15, which is characterized in that further comprise through determination
After the result of the step (b), when the test substances inhibit the expression of TNFRSF14, determine that test substances are skin beauty
The step of white substance.
18. a kind of for diagnosing the composition of the relevant skin condition of pigment, the composition includes for detecting TNFRSF14's
The reagent of mRNA or TNFRSF14 protein.
19. a kind of for diagnosing the essential information providing method of the relevant skin condition of pigment, this method includes confirming from tested
The step of TNFRSF14 expression quantity in the Skin Cell of person's separation, wherein the TNFRSF14 expression quantity is TNFRSF14
The expression quantity of mRNA or TNFRSF14 protein.
20. it is according to claim 19 for diagnosing the essential information providing method of the relevant skin condition of pigment, it is special
Sign is, this method further comprise by the TNFRSF14 expression quantity from the Skin Cell that subject separates with it is normally right
The step of being compared according to TNFRSF14 expression quantity in group Skin Cell.
21. it is according to claim 20 for diagnosing the essential information providing method of the relevant skin condition of pigment, it is special
Sign is that this method further comprises: when the TNFRSF14 expression quantity from the Skin Cell that subject separates is higher than just
When often to the TNFRSF14 expression quantity in group photograph Skin Cell, the relevant skin condition of pigment is provided and there is abnormal information.
22. the kit for diagnosing the relevant skin condition of pigment, which includes the mRNA for detecting TNFRSF14
Or the reagent of TNFRSF14 protein.
23. according to claim 22 for diagnosing the kit of the relevant skin condition of pigment, which is characterized in that the examination
Agent box further includes the specification for method described in any one of 9-21 according to claim 1.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020160122318A KR20180032955A (en) | 2016-09-23 | 2016-09-23 | A composition for skin brightening comprising TNFRSF14 inhibiting materials and a method for screening TNFRSF14 inhibiting materials |
| KR10-2016-0122318 | 2016-09-23 | ||
| PCT/KR2017/008922 WO2018056581A1 (en) | 2016-09-23 | 2017-08-17 | Composition for skin whitening comprising tnfrsf14-inhibiting material, and method for screening tnfrsf14-inhibiting material |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109789081A true CN109789081A (en) | 2019-05-21 |
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ID=61689888
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201780058733.2A Pending CN109789081A (en) | 2016-09-23 | 2017-08-17 | The method of skin lightening compositions comprising TNFRSF14 inhibiting substances and screening TNFRSF14 inhibiting substances |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JP2019529462A (en) |
| KR (1) | KR20180032955A (en) |
| CN (1) | CN109789081A (en) |
| WO (1) | WO2018056581A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102371420B1 (en) * | 2017-06-27 | 2022-03-08 | (주)아모레퍼시픽 | Composition for skin whitening comrpising tnfsf14 protein |
| CN110343755B (en) * | 2018-04-03 | 2022-08-09 | 伽蓝（集团）股份有限公司 | Method for screening active substance for regulating skin pigmentation and application thereof |
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|---|---|
| WO2018056581A1 (en) | 2018-03-29 |
| JP2019529462A (en) | 2019-10-17 |
| KR20180032955A (en) | 2018-04-02 |
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