WO2013073763A1 - 피부 미백 활성을 갖는 나이아신-펩타이드 및 그의 용도 - Google Patents
피부 미백 활성을 갖는 나이아신-펩타이드 및 그의 용도 Download PDFInfo
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- WO2013073763A1 WO2013073763A1 PCT/KR2012/006674 KR2012006674W WO2013073763A1 WO 2013073763 A1 WO2013073763 A1 WO 2013073763A1 KR 2012006674 W KR2012006674 W KR 2012006674W WO 2013073763 A1 WO2013073763 A1 WO 2013073763A1
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- nicotineoyl
- nicotinoyl
- peptide
- niacin
- nicotinyl
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
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- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
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- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06052—Val-amino acid
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- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
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- C07K5/06—Dipeptides
- C07K5/06104—Dipeptides with the first amino acid being acidic
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- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
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- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06156—Dipeptides with the first amino acid being heterocyclic and Trp-amino acid; Derivatives thereof
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- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06165—Dipeptides with the first amino acid being heterocyclic and Pro-amino acid; Derivatives thereof
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- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
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- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
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- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/081—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing O or S as heteroatoms, e.g. Cys, Ser
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- C07K5/08—Tripeptides
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- C07K5/08—Tripeptides
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
- C07K5/0823—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp and Pro-amino acid; Derivatives thereof
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- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/1008—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
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- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/1013—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing O or S as heteroatoms, e.g. Cys, Ser
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- C07K5/10—Tetrapeptides
- C07K5/1019—Tetrapeptides with the first amino acid being basic
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- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
Definitions
- Niacin-peptides having skin whitening activity and uses thereof
- the present invention relates to niacin-peptides having skin lightening activity and uses thereof.
- Human skin color depends on several factors, in particular season, race, and sex, mainly determined by the amount of melanin, carotene, and hemoglobin, of which melanin is the most decisive factor.
- Melanin is synthesized in melanocytes present in the basal layer of the skin and metastasizes to the surrounding keratinocytes to indicate human skin color.
- Abnormally low melanin causes skin lesions such as vitiligo, and on the contrary, when produced excessively, it is known to form spots and blemishes.
- Melanin is a type of amino acid tyrosine (tyrosin) acts tyrosinase (tyrosinase), because the tyrosinase is more activated by ultraviolet light, so the skin turns black when exposed to a lot of sunlight.
- tyrosinase tyrosinase
- raw materials formulated in whitening cosmetics as active inhibitors of tyrosinase include ascorbic acid (vitamin C) and derivatives thereof, lettuce extract, green tea extract, aloe extract, golden extract, kojic acid, Arbutin, oil-soluble licorice extract and niacinamide.
- vitamin C ascorbic acid
- lettuce extract green tea extract
- aloe extract aloe extract
- golden extract kojic acid
- Arbutin oil-soluble licorice extract
- niacinamide oil-soluble licorice extract
- Niacinamide is a water-soluble vitamin B3, also known as nicotinamide, a whitening functional agonist recently approved by the Food and Drug Administration. It is essential for our body and is included in foods such as green vegetables and cereals. The need for niacinamide for healthy skin has been recognized since the early 20th century. The lack of vitamin B3 in the diet leads to pellagra, an infectious disease that causes severe skin lesions. Niacinamide has been known as a vitamin (Vitamin PP) that prevents it.
- niacinamide did not show inhibition of tyrosinase and opaoxidase, and did not show melanin synthesis inhibition as measured by melanocyte culture.
- Melanosomes loaded with melanin synthesized in located melanocytes are known to have a function of transferring from melanocytes to keratinocytes through dendrites and eventually blocking the movement to the skin surface.
- Niacinamide is responsible for the transfer of melanin from these melanocytes to keratinocytes.
- niacin acetate which is used as an intermediate in the production of niacin amide, is known to remain at a certain level even after high purity of niacin amide in the process (around 20-100 PPM).
- the present inventors have tried to find a peptide that exhibits a whitening effect in a library of peptides with niacin, and found that some peptides with niacin have an effect on skin whitening by inhibiting melanin production.
- the present invention has been completed by selecting these excellent peptides.
- an object of the present invention is to provide a peptide for skin whitening.
- Another object of the present invention to provide a cosmetic composition for skin whitening.
- Another object of the present invention is to provide a skin whitening method.
- the present invention provides nicotinyl-PS, nicotinyl-EQ, nicotinoyl-ET, nicotinoyl-FP, nicotinoyl-NI, nicotinoyl-NL, nicotinoyl -NP, Nicotineoyl NY NY Nicotineoyl -PG, Nicotineoyl -QI, Nicotineoyl -VA, Nicotineoyl -VF Nicotineoyl -VS, Nicotineoyl -VT, Nicotineoyl -WM, Nicotine Tinoyl -YR, Nicotineoyl -YT, Nicotineoyl -AHK, Nicotineoyl -FWY Nicotineoyl -GHR Nicotineoyl -GPHyp, Nicotineoyl -TYR, Nicotineoyl -YGY Nicotineoyl -PLG, Nicotineoyl
- the present inventors have tried to find a peptide that exhibits a whitening effect in the peptide library in which niacin is bound, and found that some peptides in which niacin is bound have an effect on skin whitening by inhibiting melanin production.
- the present inventors provide a peptide of the present invention by preparing various peptide libraries containing niacin at the N-terminus and preparing candidate peptides, and then screening peptides excellent in melanogenesis inhibitory activity among candidate peptides.
- peptide refers to a linear molecule formed by binding amino acid residues to each other by peptide bonds
- niacin-peptide refers to a form in which niacin is bonded to the N-terminus of the peptide.
- Peptides of the invention can be prepared according to chemical synthesis methods known in the art, in particular solid-phase synthesis techniques (Merrifield, J. Amer. Chem. Soc. 85: 2149-54 (1963) Stewart, et al., Solid Phase Peptide Synthesis, 2nd.ed., Pierce Chem. Co .: Rockford, 111 (1984)).
- the peptide of the present invention can induce modification by binding niacin to the N-terminus.
- the peptide of the present invention may have high half-life due to increased stability upon in vivo administration.
- an amino group (-N3 ⁇ 4) may be bonded to the C-terminus of the peptide to induce modification. Modification of the above-mentioned amino acid serves to greatly improve the stability of the peptide of the present invention.
- stability herein means not only in vivo stability but also storage stability (eg, room temperature storage stability).
- the protecting group described above serves to protect the template of the present invention from the attack of protein cleavage enzymes in vivo.
- the peptide of the present invention does not show toxicity to human-derived cells and thus has high utility as a peptide for skin whitening.
- the present invention as a result of treatment of niacin-peptide to HaCat cells and NIH3T3 cells at a concentration of 10 ng / m 1-100 ug / ml, no significant cytotoxicity was measured and even when the cell morphology was visually confirmed. No change was observed (FIG. 9),
- the niacin-peptide exhibits excellent thermal stability even at a temperature of 40 ° C. (FIG. 3), and has higher stability in serum (FIG. 4) than the peptide without niacin attached (FIG. 4). Therefore, the peptide of the present invention can be advantageously applied to products requiring long-term storage, such as pharmaceuticals, quasi-drugs and cosmetics.
- the peptide of the present invention has melanin production inhibitory ability.
- the melanin cells were treated with ⁇ -MSH to induce melanin production, and then the melanin production was compared after incubation with the peptides of the present invention. It was inhibited about 4-44% (Table 1). More specifically, the inhibition of melanin production was 403 ⁇ 4 when treated with nicotinyl-ET, 30% when treated with nicotinyl-PG, 44% when treated with nicotinyl-PS, and nicotinyl-VS. When treated, it was found to be 353 ⁇ 4.
- the peptides of the invention increase the production of melanin concentration-dependently.
- niacin-peptide (NA-PS) and niacin-binding peptides were treated to cells at different concentrations (1 ug / ml, 10 ug / ml, 100 ug / ml, 250 yg / ml).
- concentration-dependent treatment with niacin-peptide FIG. 5
- niacin-peptide (nicotinoyl-PG ⁇ nicotinoyl— PS Nicotinoyl-ET, Nicotinoyl-VS), niacin-binding peptide (PG, PS, ET, VS), arbutin and M2G by concentration (1 ug / ml, 10 ug / ml, 100 ug / ml, 250 yg / ml) and incubated for 3 days, the absorbance of the culture was measured at 490 nm. As a result, it was confirmed that melanin production was significantly reduced in niacin-peptide compared to the peptide to which niacin was not bound. (FIG. 6).
- the peptide of the present invention inhibits the activity of tyrosinase.
- the absorbance was measured at 475 nm to confirm the inhibition rate for tyrosinase
- niacin-peptide showed a significant inhibitory effect on tyrosinase activity compared to the peptide and arbutin to which niacin is not bound (FIG. 7).
- the peptide of the present invention is TRP-1 (tyros inase-related protein-1), TRP ⁇ 2 (tyrosinase one related protein-2) and MITF (Mi crophthalmi a-associ ated transcription factor) Inhibits the expression).
- Melanin is produced by a series of enzymatic reactions such as tyrosinase, TRP-1, TRP-2 (Olivares et al,, Pigment Cell Melanoma Res 22 (6): 750-760 (2009)),
- the mechanism is the proliferation of melanocytes and an increase in tyrosinase enzyme activity.
- the most important enzyme in melanogenesis is tyrosinase, a rate-regulating factor that catalyzes the early stages of melanin biosynthesis by tyrosine 3,4-dihydroxyphenylphenyl alanine (DOPA) and D0PA quinones.
- Red eumelanin and brown pheomelanin are synthesized (Lopezet et al., J Biol Chem 267: 381-390 (1992)).
- Two other important enzymes for eumelanin formation are TRP-1 and TRP-2.
- MI crophthalmi a-associated transcription fact is a major factor responsible for the transcription of tyrosinase and related enzymes (TRPs), and melanin production is inhibited when MITF, T P-1 and TRP-2 expression is suppressed. It can be said that it is suppressed.
- melanocytes have a— MSH and peptides (PG, PS, ⁇ , VS) or ⁇ -MSH and niacin-peptides (nicotinoyl-PG, nicotinoyl-PS, nicotinoyl-ET, nicotine).
- Tinoyl-VS was treated by concentration (1 g / ml, 10 ug / ml, 50 U g / ml) and cultured for 4 days, and then mRNA was obtained from the cells to perform reverse transcriptase polymerase chain reaction.
- the present invention provides nicotinyl-PS, nicotinyl-EQ, nicotinoyl-ET, nicotinoyl-FP, nicotinoyl-NI, nicotinoyl-NL, nicotinoyl -Nicotineoyl -NY, Nicotineoyl -PG, Nicotineoyl -QI, Nicotineoyl-VA, Nicotineoyl -VF, Nicotineoyl -VS, Nicotineoyl -VT, Nicotineoyl- ⁇ , Nicotineoyl -YR, Nicotineoyl _YT, Nicotineoyl - ⁇ , Nicotineoyl -FY, Nicotineoyl -GHR, Nicotineoyl -GPHyp, Nicotineoyl -TYR, Nicotineoyl -YGY, Nicotineo Days -PLG, nicotin
- composition of the present invention can be made into a cosmetic composition.
- Niacin -peptide used as an active ingredient in the composition of the present invention is composed of 2 to 6 amino acid residues very small molecular weight is very excellent skin penetration rate. Therefore, topically application of the composition of the present invention to the skin High skin penetration rates can achieve skin whitening effects. Since the composition of the present invention inhibits the production of melanin, the skin color is brightened and the skin tone is constant, and it is effective for removing skin pigments and removing blotch. The niacin-peptide of the present invention suppresses the production of melanin pigment in keratinocytes by various processes and exerts the effect of brightening the color of the skin keratinocyte layer by preventing or attenuating the release of melanin previously produced from keratinocytes.
- the components included in the cosmetic composition of the present invention include components conventionally used in cosmetic compositions in addition to nicotinyl-peptide as an active ingredient, and conventional auxiliaries such as stabilizers, solubilizers, vitamins, pigments and flavorings, and Carrier.
- the cosmetic composition for skin whitening of the present invention may be prepared in any formulation commonly prepared in the art, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactants It may be formulated as a containing cleansing oil, powder foundation, emulsion foundation, wax foundation, spray, and the like, but is not limited thereto. More specifically, it may be prepared in the form of a flexible lotion, nutrition lotion, nutrition cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder.
- the carrier components include animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide. Can be used.
- the carrier component is lactose, talc, silica, aluminum hydroxide .
- Calcium silicate or polyamide powder may be used, and especially in the case of a spray, may additionally include propellants such as chlorofluorohydrocarbons, propane / butane or dimethyl ether.
- a solvent, a solubilizer or an emulsifier is used as the carrier component, for example water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl Benzoate, propylene glycol, 1,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid ester.
- the carrier component is water, a liquid diluent such as ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspending agent such as polyoxyethylene sorbitan ester and polyoxyethylene sorbitan ester, Microcrystalline cellulose, aluminum metahydroxy bentonite, agar or tracant and the like can be used.
- the carrier component is an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, isethionate, an imidazolinium derivative, a methyltaurate, a sarcosinate, a fatty acid amide.
- Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters, etc. may be used.
- the present invention is effective Nicotineoyl-PS, Nicotineoyl-EQ Nicotineoyl-ET, Nicotineoyl-FP, Nicotineoyl-NI, Nicotineoyl-NL Nicotineoyl-NP, Nicotineoyl-NY, Nicotineo Sun -PG, Nicotineoyl -QI Nicotineoyl -VA, Nicotineoyl- VF, Nicotineoyl- VS, Nicotineoyl -VT Nicotineoyl— ⁇ , Nicotineoyl -YR, Nicotineoyl -YT, Nicotineoyl -AHK Nicotineoyl— FWY, Nicotineoyl -GHR, Nicotineoyl -GPHyp : Nicotineoyl -TYR Nicotineoyl -YGY, Nicotineoyl- PLG, Nicotineoyl — PLG-NH 2 , Nicotinyl-beta-AHSH
- niacin-peptide of the present invention exhibits an excellent effect on skin whitening by inhibiting melanin production.
- the peptide of the present invention is very excellent in stability and skin permeability.
- the cosmetic composition comprising the peptide of the present invention exhibits very good efficacy on skin whitening.
- Figure 2 is a graph showing the results of high performance liquid chromatography analysis on niacin-peptide.
- Figure 3 is a graph showing the results of measuring the thermal stability of niacin-peptide.
- FIG. 4 is a graph showing a result of comparing and measuring the stability of niacin-peptide in human serum.
- FIG. 5 is a picture comparing the effect of reducing the melanogenesis of melanocytes after treatment with niacin-peptide to ⁇ -MSH treated B16F10 cells.
- Figure 6 is a graph confirmed by measuring the melanin reduction after treatment with niacin-peptide to a-MSH treated B16F10 cells.
- FIG. 7 is a graph showing the results of measuring the activity of tyrosinase after treatment with niacin-peptide in a-MSH-treated B16F10 cells.
- FIG. 8 after treatment with niacin-peptide in a-MSH treated B16F10 cells, mRNA extraction and reverse transcription using melanin marker marker primers The figure shows the result of polymerase chain reaction.
- FIG. 9 is a graph showing the results of cytotoxicity by treating niacin-peptide to NIH3T3, HaCat and B16F10 cells. [Specific contents for implementation of the invention]
- Fmoc-amino acids Fmoc ⁇ Ala, Fmoc— Arg (pbf), Fmoc—Asp (OtBu), Fmoc—As (trt), Fmoc—Gly, Fmoc-Glu (OtBu) to synthesize a library of peptides.
- the prepared niacin-peptidyl resin was washed three times with DMF, MC, and methanol, dried by slowly blowing nitrogen air, and dried completely under reduced pressure under vacuum under P 2 0 5 .
- a fugitive solution in the prepared resin [trifluoroacetic acid (1 1 ⁇ 0 ⁇ acid: TFA) 81.5%, distilled water 5%, thioanisole (5%), phenol 5%, EDT (1,2-Ethanedi thiol ) 2.5% and 1% of TIS (Triisopropylsilane)] was added to 30 ml, and then shaken occasionally at room temperature to maintain a reaction for 1 hour in an ice bath.
- the whitening peptide was searched for by using the niacin-peptide (NA—peptide) library synthesized in Example 1 to reduce the production of melanin pigment.
- Activity detection of whitening was carried out by culturing B16F10 (Korea Cell Line Bank) melanin cells and inducing melanin production with ⁇ -MSH (a ⁇ melanocyte stimulating hormone (Sigma)), and then inhibiting melanin production against the library peptide.
- the melanocytes of the mice were cultured at 37 ° C. and 5% CO 2 with medium containing 10% fetal bovine serum (Sigma) in DMEMGXilbecco's modified Eagle's media (Sigma).
- the control group was treated with nothing but the solvent, and the positive control group received ⁇ -MSH. 20 ⁇ / ⁇ 1 and the rest of the dish were treated with a _MSH 20 g / nil and 10 ng / ml of peptide. Incubated for 3 days. After removing the culture medium by centrifugation, the melanin production of the cells was visually confirmed.
- Inhibition rate of melanin production for each peptide synthesized in Example 1 Measured at UV490. Calculation of the inhibition rate is shown in Table 1 the difference in melanin absorbance of the peptides measured based on the melanin absorbance of the positive control treated with a-MSH only.
- Candidate peptides that showed good titer by screening were divided into separate groups and synthesized in large quantities in 100 umole units. 1 shows the results of screening niacin—peptide.
- Figure 2a-c is a result of high performance liquid chromatography and MALDI-Tof mass spectrometry for NA-VS, NA-PS and NA-ET in the library peptide showing the whitening effect, on the other hand, to confirm the stability of the prepared peptide, HPLC
- the peptide was dissolved in a 50 mM Tris-HCKpH 8.0) complete solution so that 98% or more of high purity nicotinyl-VS, nicotinyl-PS and nicotinoyl-ET peptides purified purely were 100 yg / ml.
- niacin-peptide was stored at 40 ° C for 7, 14, 21, 28, 35, 42 and 60 days and the heat loss was measured. It was confirmed that it has a high stability in the storage period (Fig. 3).
- niacin-peptide was in human serum. The amount of peptide remaining in the serum after treatment with niacin-peptide (nicotinoyl-PS, 100 ug / ml) or peptide without niacin (PS, 100 yg / ml) in human serum and incubated for 10 hours. was measured hourly.
- niacin-peptide After treating niacin-peptide by concentration, melanin production inhibitory effect was measured.
- Melanocytes in mice are found in DMEM (Dulbecco's modified Eagle's). media, Sigma) was incubated at 37 ° C, 5% C0 2 conditions with the addition of 10% fetal bovine serum (Sigma).
- the control group was treated with nothing but the solvent, and the positive control group received ⁇ -MSH 20 g / ml, and the rest of the dish contains a-MSH 20 yg / nil and niacin-peptide (NA-PG, NA-PS, NA-ET, NA-VS) and Arbutin and AA2G as controls, 1 g / ml, 10 pg It was treated to a concentration of / ml, 100 ug / ml, 250 g / ml. Each dish was added with test substance and incubated for 3 days. After 3 days, the culture was removed by centrifugation, and the melanin production of the cells was visually confirmed.
- 5 is a photograph of the generated melanocytes confirming the rate of decrease in melanin production according to each treatment concentration for the peptide of NA-PS and PS, the cell number is relatively reduced compared to the treatment with a-MSH, arbutin At the same concentration, the number of cells decreased rapidly. The color of the medium became clear compared to the number of cells, indicating that the melanin production was inhibited.
- the tyrosinase enzyme was extracted from mushrooms, and a sigma company was used. First, L-tyrosine, a substrate, was dissolved in a phosphate buffer solution (0.05 M, pH 6.8) to a concentration of 1.5 mM. Then, 0.01 ml of this solution was added to a 0.3 ml volumetric spectrophotometer cuvette and a cofactor. Phosphorus waveguide was added at a concentration of 0.06 mM and 0.01 ml. The peptide of the present invention was added thereto, and the phosphate complete solution was added to make 0,1 ml. An enzyme in which tyrosinase was dissolved at 60 U / mL in a phosphate buffer solution.
- the reaction was advanced by adding 0.1 ml of the solution. And arbutin and nicotinoyl -PS and PS peptides were used by 100 ppm each compared to the experiment. At this time, as a control (blank), only 0.1 ml of buffer instead of tyrosinase was added.
- TRP-Ktyrosinase—related protein-1 (TPP), tyrosinase-related protein— 2) and RNA production of mi crophthalmi a-associated transcript ion factor (MITF) was confirmed by real-time reverse transcriptase polymerase chain reaction (qRT-PCR).
- TRP-1 is FTTGG CCC AGG ATC AGT AGG T) / R (CAT CAA CAC TTC CAG CA)
- TRP-2 is F (GGC TAC AAT TAC GCC GTT G) / R (CAC TGA GAG AGT TGT GGA CCA A)
- MITF F (CTT AAC TCC AAC TGT GAA AAA GAG G) / R (CAT ACC TGG GAC TCA CTC TO
- standard gene is GAPDH
- F (GAG CCA AAC GGG TCA TCA) / R (CAT ATT CG TGG TTC ACA CC) was used.
- the experimental results confirmed that the niacin-peptide of the present invention concentration-dependently inhibited the expression of TRP-1, TRP
- keratinocyte toxicity to the peptide of the present invention, refer to the method of Rigino et al. (Rizzino, et al. Cancer Res., 48: 4266 (1988)), HaCat cells (Korean cell line). MTT assay using NIH3T3 cells (Korea Cell Line Bank). Each cell line was cultured using EMEM (Eagle's minimal essential media, Gibco) containing 10% FBS (fetal bovine serum). The cultured cell line was removed from the bottom of the culture vessel with 0.25% trypsin solution and centrifuged to collect only cell precipitates.
- EMEM Eagle's minimal essential media, Gibco
- FBS fetal bovine serum
- Nicotinoyl -VS, nicotinoyl- showing the efficacy of whitening in the above embodiment 50 mg of PS, nicotinoyl-ET and nicotinoyl-PG peptides were accurately quantified and dissolved by diluting with 500 ml of distilled water.
- the niacin-peptide solution was mixed with 5 g of hydrolyzed lecithin and a slight oil phase, and then adjusted to distilled water so that the total amount was 1 L, and then emulsified using a high pressure microfluidizer to a size of about 100 nm.
- Nanosomes were prepared. The prepared nanosomes were used for cosmetic production with a final concentration of about 50 ppm.
- Example 9 flexible cosmetics
- Niacin-peptide-like nanosomes prepared in Example 2 containing one or a plurality, and the flexible cosmetics made of the following composition was prepared according to a general lotion preparation method.
- Example 10 nourishing cream
- Niacin-peptide-like nanosomes prepared in Example 2 containing one or a plurality, nutrition cream consisting of the following composition was prepared according to the general nutrition cream manufacturing method. [Table 3]
- Example 11 nutrient lotion
- Niacin-peptide-like nanosomes prepared in Example 2 containing one or a plurality, nutrient cosmetics consisting of the following composition was prepared according to a general lotion manufacturing method.
- Niacin-peptide-like nanosomes prepared in Example 2 comprising one or a plurality, essence consisting of the following composition was prepared according to the general essence preparation method.
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US14/359,114 US9456972B2 (en) | 2011-11-18 | 2012-08-22 | Niacin-peptide having skin whitening activity and use for same |
CN201280056913.4A CN103957914A (zh) | 2011-11-18 | 2012-08-22 | 具有皮肤美白效果的烟酸-肽和其用途 |
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KR1020110121135A KR101167285B1 (ko) | 2011-11-18 | 2011-11-18 | 피부 미백 활성을 갖는 나이아신-펩타이드 및 그의 용도 |
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US9456972B2 (en) | 2011-11-18 | 2016-10-04 | Sung-Ae Choi | Niacin-peptide having skin whitening activity and use for same |
WO2017116138A1 (ko) * | 2015-12-28 | 2017-07-06 | 주식회사 젬백스앤카엘 | 멜라닌 억제 기능성 펩티드 및 이를 포함하는 조성물 |
US10729628B2 (en) | 2015-12-24 | 2020-08-04 | Conopco, Inc. | Tyrosinase inhibitors |
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- 2012-08-22 CN CN201280056913.4A patent/CN103957914A/zh active Pending
- 2012-08-22 CN CN201510536542.5A patent/CN105085611B/zh active Active
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US20150037268A1 (en) | 2015-02-05 |
CN105085611A (zh) | 2015-11-25 |
US9456972B2 (en) | 2016-10-04 |
KR101167285B1 (ko) | 2012-07-23 |
CN105085611B (zh) | 2019-07-19 |
CN103957914A (zh) | 2014-07-30 |
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