CN105362088A

CN105362088A - A kind of polypeptide composition for whitening, lightening skin and lightening spots

Info

Publication number: CN105362088A
Application number: CN201510974505.2A
Authority: CN
Inventors: 丁文锋
Original assignee: SHENZHEN WINKEY MEDICAL RESEARCH DEVELOPMENT CO LTD
Current assignee: Yupi Biology (dongguan) Co Ltd
Priority date: 2015-12-22
Filing date: 2015-12-22
Publication date: 2016-03-02
Anticipated expiration: 2035-12-22
Also published as: CN105362088B; CN109998938B; CN109998938A

Abstract

The present invention provides a group of polypeptide compositions for whitening and removing spots, comprising a combination of MC1-R antagonists (i.e., α-MSH competitive antagonists) and/or polypeptides that inhibit α-MSH expression and/or tyrosinase inhibitors, the polypeptide compositions can reduce the production of melanin, help brighten the skin tone, achieve the purpose of lightening spots (chloasma, butterfly spots, freckles, etc.), improving dullness, and whitening skin quality. The concentration of each polypeptide is 0.0001%-5%, and the composition of the present invention can be prepared into various beauty and skin care products and medical products.

Description

A kind of peptide composition for the light speckle of the bright skin of whitening

Technical field

The invention belongs to medical cosmetic product field, relate to a kind of peptide composition for the light speckle of the bright skin of whitening, adopt the method for composite reactive polypeptide to prepare various dosage form and comprise cream, essence, emulsion, lyophilized powder, facial film etc., be used for the treatment of mottle (chloasma, butterfly spot and freckle etc.) problem, low and deep to reach improvement, brighten the object of skin quality.

Background technology

The background information comprised understanding the present invention and coming in handy below is described.But neither admit that any information provided at this is the present invention claimed at present or the prior art about application, any concrete or implicit disclosed prior art related to neither be admitted.

Melanin has the greatest impact to skin color, forms route in skin as follows: ultraviolet radiation, the angle albuminous cell of induced skin epidermis can produce melanotropin precursor (POMC)/melanotropin (a-MSH) and interleukin.A-MSH is a kind of endogenous neural peptide, after combining with melanocyte surface melanocortin receptor-1 (MC1-R), the generation of modulating melanin, its process is: a-MSH is in conjunction with after MC1-R, activated adenyl cyclase, then cause cAMP in cell to increase, the further activated protein kinase C of cAMP (PKC) of increase, by the tyrosine kinase in the final activation of melanocyte of PKC.Under the effect of tyrosine kinase, generation DOPA, DOPA quinone finally form melanin.Melanin along with the metabolism arrival skin surface of horn cell, thus causes skin surface color burn, or speckle appears in local.

Early stage for the oxidant (sodium hypochlorite and hydrogen peroxide) in freckle removing and whitening though, mercurous material and hydroquinone Be very effective, its toxic and side effects is eliminated comparatively greatly.Existing widely used is Arbutin, kojic acid, vitamin C derivatives and some Chinese medicine extract etc., and its principle is as tyrosinase inhibitor, stops melanic accumulation, thus reaches the effect of desalination skin color.But vitamin C is unstable, is not easily absorbed by the skin, is difficult to extensive use; Arbutin is a kind of compound containing phenolic group, although safety, slow to the depression effect of tryrosinase, and light absorptive is good, is not suitable for using daytime; Kojic acid is the most obvious composition of existing whitening and speckle dispelling effect, obtaining, containing certain toxicity, not advising life-time service by refining in the fermentation liquid of Eurotium and Penicillium; Chinese medicine extract is then still needed and more to be furtherd investigate drug effect; Symwhite-337 is a kind of compound found in recent years, and its restraint of tyrosinase active effect is stronger than kojic acid/Arbutin.

On market, the large portion of the product of whitening is tyrosinase inhibitor, and melanic the way of production is very complicated, and the effect of light speckles, beautification and white is not also very desirable.Then a lot of at the product ground, such as prior art CN101631532A is supplied to a kind of whitening combination, and it at least comprises: MC1-R acceptor inhibitor; The tyrosinase inhibitor that vitamin C is derivative; Dark volume is transferred to Keratinocytic inhibitor; The invention still further relates to its in cosmetics and dermatological in application, for the preparation of the depigmentation compositions making skin whitening and/or light.CN101917961A provides a kind of topical cosmetic composition, it is characterized in that, it comprises at cosmetics carrier: the medicament of at least one restriction α-MSH and MC-1 receptors bind, the medicament of at least one restriction ET-1 synthesis, at least one suppresses the medicament of SCF synthesis, and at least one suppresses the medicament of tyrosine activity.

Research worker, on the basis of improving existing whitening composition deficiency, is continually developed the product of novel whitening, speckle dispelling, is become focus with the new product development that biological polypeptide and modern high and new technology combine.Polypeptide is the natural active matter be connected to form by covalent peptide bonds by two or more aminoacid, be a kind of material be between amino acid and protein, with body substance homology, and molecular weight is little, its biochemical physiological mechanism is clear and definite, is to generally acknowledge safer beauty and skin care raw material at present.The present invention is then the difference in functionality utilizing polypeptide, as the material of expressing as MC1-R antagonist (i.e. α-MSH competitive antagonist), tyrosinase inhibitor, suppression α-MSH/generating, be combined to form polypeptide complex, give full play to the impact of polypeptide in melanin generates, to reach the effect of whitening and speckle dispelling.

Summary of the invention

Based on prior art Problems existing, the present invention is the principle generated according to melanin, in view of the existing whitening and speckle dispelling product in market, the applicant is by a large amount of experiments, adopt one or more polypeptides in combination that tool MC1-R antagonist (i.e. α-MSH competitive antagonist) and/or tyrosinase inhibitor and/or α-MSH express/generate, reach the effect of whitening and speckle dispelling from each approach of check melanin generation in more fully mode.

The invention provides a kind of peptide composition for whitening and speckle dispelling, it is characterized in that, one or more polypeptide comprising MC1-R antagonist (i.e. α-MSH competitive antagonist) and one or more polypeptide suppressing α-MSH to express/generate combine, or one or more polypeptide of MC1-R antagonist (i.e. α-MSH competitive antagonist) and one or more polypeptide of tyrosinase inhibitor combine, or one or more polypeptide of MC1-R antagonist (i.e. α-MSH competitive antagonist), one or more polypeptide three combination that one or more polypeptide of tyrosinase inhibitor and suppression α-MSH express/generate, all kinds of polypeptide is as follows:

(1), one or more following polypeptide of MC1-R antagonist (i.e. α-MSH competitive antagonist) are selected from,

Include but not limited to nonapeptide-1, six peptides-2;

(2), be selected from one or more following polypeptide of tyrosinase inhibitor, include but not limited to decapeptide-12;

(3), be selected from one or more the following polypeptide suppressing α-MSH to express/generate, include but not limited to tetrapeptide-27;

Wherein, the mass concentration of each component materials is 0.0001%-5%.

The present invention, from chromogenesis principle on, researches and develops a kind of product of whitening and speckle dispelling, mainly acts on bright color, desalinates mottle on the face, and described peptide composition can be following combination:

Peptide composition of the present invention can be that nonapeptide-1 and tetrapeptide-27 combine, and nonapeptide-1 and decapeptide-12 combine, nonapeptide-1 and the combination of six peptides-2;

Peptide composition of the present invention can be the combination of nonapeptide-1, tetrapeptide-27 and decapeptide-12;

Peptide composition of the present invention can be the combination of nonapeptide-1, tetrapeptide-27, six peptides-2 and decapeptide-12;

Peptide composition of the present invention can add the polypeptide of some inhibiting expression of tyrosinase gene, and as oligopeptide-68, polypeptide moiety mass concentration is 0.0001%-5%.

In the present invention, peptide composition also can add some other tyrosinase inhibitors, and (commodity are called to comprise Symwhite-337 377), Arbutin, kojic acid, vitamin C derivatives, mass concentration is 0.001%-5%.

The present invention adds a kind of other skin care actives, mass concentration is 0.001%-5%, and described active substance is selected from and extracts lipid and/or synthesis lipid, gelling with polymer that is thickness, surface-active and emulsibility, water or fat-soluble active ingredient, plant extract, tissue extract, marine extracts, sintetics, sunscreen products, antioxidant, wetting agent and screening agent and/or make skin reply the active substance of vigor.

The present invention includes interpolation wetting agent, preferably as glycerol, Aloe glue, hyaluronic acid etc.; Many alcohols antiseptic, preferred caprylyl glycol; Comprise the comprehensive reagent that anti-microbial type maintains stable components, preferably 1,2-hexanediol; The mass concentration of each component is 0.001%-5% (w/w) etc. above.

The present invention includes pH adjusting agent, described pH adjusting agent is selected from: triethanolamine, sodium bicarbonate, potassium bicarbonate, preferred triethanolamine; Composition pH scope is 3.0 ~ 8.0, preferred 5.0-7.0.

The present invention adopts composite polypeptide compositions, can be applied to the reparation that after shining, the colour of skin highlights, the treatment of various mottle (chloasma, butterfly spot and freckle etc.).

Peptide composition of the present invention can make various dosage form, as development dosage form mainly contains essence, powder (capsule, lyophilized powder), Emulsion, cream, gel, facial film, dressing etc.; Product can be facial masks for whitening faces and removing spots, whitening and moisturizing elite, eye or face's speckle dispelling elite, whitening cream etc.

Understand the present invention to more be conducive to, the mechanism of action principle of each peptide species is as follows:

Nonapeptide-1 is a kind of bionical polypeptide to anti alpha-MSH mechanism of action, by with α-MSH competition binding MC1-R, thus reduce melanin generation, melanin is stoped excessively to produce, for MC1-R inhibitor, i.e. α-MSH competitive inhibitor, the product of reference is Melanostatin-5, is market uses the most much higher peptide product of the most extensive popularity for Whitening, spot.

Six peptides-2 are a kind of polypeptide with whitening effect obtained by synthesis, by with α-MSH competition binding MC1-R, thus reduce melanic generation, form product Dermostatyl at present ^tMiS.The local color of existing patent of invention CN1494886A is adjusted in one of shallow compositions and is added six peptides-2 as the competitive antagonist of a-MSH, and skin color is shoaled.Six peptides-2 are also MC1-R inhibitor, i.e. α-MSH competitive inhibitor,

Decapeptide-12 is a kind of synthetic peptides comprising arginine, lysine, tryptophan, tyrosine, serine, can remarkable restraint of tyrosinase activity.The people such as AbuUbeid have confirmed that decapeptide-12 is a kind of tyrosinase inhibitors more more effective than hydroquinone, and do not produce toxicity like hydroquinone to melanocyte.The people such as AndreaT.Kassim at Open-labelevaluationoftheskin-brighteningefficacyofaskin-brighteningsystemusingdecapeptide-12, J, JournalofCosmeticandLaserTherapy, 2012; Also confirm in 14:117 – 121 that decapeptide-12 is by the activity of restraint of tyrosinase thus the generation of check melanin.

Tetrapeptide-27 can suppress because of ultraviolet radiation induction α-MSH/POMC and interleukin express, thus make melanin generate reduce, reach whitening effect, formation product is Tego-pep-4Even.

The present invention comprises relative to the beneficial effect acquired by prior art:

The present invention finds in clinical trial, the bionical polypeptide of some antagonisms a-MSH mechanism of action, as nonapeptide-1, can with a-MSH competitive binding MC1-R, thus reduce melanin generate, be MC1-R antagonist (i.e. a-MSH competitive antagonist).Other polypeptide can the activity of restraint of tyrosinase, as decapeptide-12, is tyrosinase inhibitor, has white-skinned face function.So a kind of desirable whitening and speckle dispelling product composition, the approach that should generate from melanin, both containing a-MSH competitive antagonist composition, the composition again containing tyrosinase inhibitor, had reached the effect of whitening and speckle dispelling from each approach of check melanin generation.Clinical data shows, and these combinations have more effective whitening and speckle dispelling effect than single polypeptide, and show obvious synergism, this will make up the deficiency of whitening and speckle dispelling product.

In embodiment of the present invention tyrosine test experiments, embodiment 1, embodiment 2, embodiment 3, embodiment 4 peptide composition group and comparative example 1 is adopted to show in tryrosinase testing experiment, peptide composition group, than the better effects if of single polypeptide restraint of tyrosinase activity, shows obvious synergism.Its mechanism is, these different polypeptide, from the complicated approach of B16 cell, the reaction terminating in downstream is caused with α-MSH competitive binding MC1-R, or suppress α-MSH express/generate so that reduce in conjunction with MC1-R, reduce the physiological reaction in downstream, thus the activity of further restraint of tyrosinase; Or directly act on tryrosinase and suppress it active.In clinical experiment, volunteer adopts the polypeptide of embodiment 1, embodiment 2, embodiment 3, embodiment 4 peptide composition group and comparative example 1 respectively, every day smears twice, 28 days and within 56 days, carry out the detection of skin colorimetric parameter, discovery effectively can desalinate mottle, and its peptide composition group has more obvious effect than single polypeptide.

Accompanying drawing explanation

Fig. 1 is the schematic diagram suppressing tyrosine activity for Whitening, spot;

Fig. 2 is the schematic diagram (28 days) for the clinical real test desalination mottle of Whitening, spot;

Fig. 3 is the schematic diagram (56 days) for the clinical real test desalination mottle of Whitening, spot.

Detailed description of the invention

For a better understanding of the present invention, below in conjunction with embodiment and accompanying drawing, invention is described in detail, but has more than and be limited to following embodiment.

Embodiment 1 Whitening, spot essence

Prescription (1 kilogram of essence):

Collocation method:

Be added to the water by the hyaluronate sodium of formula ratio, stir and make mix homogeneously, be then heated to 80 ~ 85 DEG C, insulated and stirred makes it be uniformly dispersed.Temperature drops to less than 40 DEG C, adds glycerol, Aloe glue, nonapeptide-1, decapeptide-12, Symwhite-337, hyaluronate sodium, caprylyl glycol and 1,2-hexanediol, stirs.Adjust the pH value to 5.5 of solution with 15% triethanolamine about.

Embodiment 2

Prescription (1 kilogram of essence):

Collocation method:

Be added to the water by the hyaluronate sodium of formula ratio, stir and make mix homogeneously, be then heated to 80 ~ 85 DEG C, insulated and stirred makes it be uniformly dispersed.Temperature drops to less than 40 DEG C, adds glycerol, Aloe glue, nonapeptide-1, tetrapeptide-27, Symwhite-337, hyaluronate sodium, caprylyl glycol and 1,2-hexanediol, stirs.Adjust the pH value to 5.5 of solution with 15% triethanolamine about.

Embodiment 3

Prescription (1 kilogram of essence):

Collocation method:

Be added to the water by the hyaluronate sodium of formula ratio, stir and make mix homogeneously, be then heated to 80 ~ 85 DEG C, insulated and stirred makes it be uniformly dispersed.Temperature drops to less than 40 DEG C, adds glycerol, Aloe glue, nonapeptide-1, tetrapeptide-27, oligopeptide-68, Symwhite-337, hyaluronate sodium, caprylyl glycol and 1,2-hexanediol, stirs.Adjust the pH value to 5.5 of solution with 15% triethanolamine about.

Embodiment 4

Prescription (1 kilogram of essence):

Collocation method:

Be added to the water by the hyaluronate sodium of formula ratio, stir and make mix homogeneously, be then heated to 80 ~ 85 DEG C, insulated and stirred makes it be uniformly dispersed.Temperature drops to less than 40 DEG C, adds glycerol, Aloe glue, nonapeptide-1, tetrapeptide-27, oligopeptide-68, six peptides-2, decapeptide-12, Symwhite-337, hyaluronate sodium, caprylyl glycol and 1,2-hexanediol, stirs.Adjust the pH value to 5.5 of solution with 15% triethanolamine about.

Comparative example 1

Prescription (1 kilogram of essence):

Collocation method:

Be added to the water by the hyaluronate sodium of formula ratio, stir and make mix homogeneously, be then heated to 80 ~ 85 DEG C, insulated and stirred makes it be uniformly dispersed.Temperature drops to less than 40 DEG C, adds glycerol, Aloe glue, nonapeptide-1, Symwhite-337, hyaluronate sodium, caprylyl glycol and 1,2-hexanediol, stirs.Adjust the pH value to 5.5 of solution with 15% triethanolamine about.

Embodiment 5 tryrosinase test experiments

Material: melanocyte, CO ₂incubator, enzyme-linked immunosorbent assay instrument, centrifuge; Levodopa (L-Dopa), dimethyl sulfoxide (DMSO), trypsin, TtitonX-100, be Sigma product.

Experimental procedure: melanocyte is cultivated 4 days with embodiment 1, embodiment 2, embodiment 3, embodiment 4 respectively together with comparative example 1, adds normal saline group as baseline group.Albumen in isolated cell also marks with levodopa (L-Dopa).The light absorption value of L-Dopa is surveyed, assessment tyrosinase activity at 405nm place.

Tyrosinase activity=amountofL-DOPA tyrosinase activity=levodopa amount

Data show, and the effect of peptide composition group restraint of tyrosinase of the present invention, as shown in Figure 1, is better than single peptide composition group, and this display peptide composition group shows obvious synergism.

Embodiment 6 clinical trial---white-skinned face function is tested

Choose 150 volunteers, the age, everyone had a dark speckle on the face at least between 33-55 year.Use embodiment 1, embodiment 2, embodiment 3, embodiment 4 and comparative example 1 for one day twice, often organize 30 people, continuous 58 days.

Colorimetric measurement method: with spectrophotometer in D0, D28, D56 analyzing skin colorimetric parameter (L*)

Skin colorimetric parameter (L*): refer to and to contrast with pure white object of reference, the brightness value that subject observes, wherein L* (brightness) namely refers to the brightness range from black (L=0) to pure white (L=100).

Data show, 100% experimenter's colour of skin luminance raising, and after surrounding, bright skin effect is obvious especially, and the percentage ratio that each group colour of skin brightens is as Fig. 2 and Fig. 3.Use after 56 days, the effect that skin brightens is more obvious than 28 days.

Above content is the further detailed description done the present invention in conjunction with concrete preferred implementation, but does not represent that specific embodiment of the invention is confined to these explanations.Belonging to the present invention, restrain the those of ordinary skill led, without departing from the inventive concept of the premise, some simple deductions or replacement can also be made, all should be considered as belonging to protection scope of the present invention.

Claims

1. A polypeptide composition for whitening and freckle removal, characterized in that it comprises: one or more polypeptides of MCl-R antagonists (i.e. α-MSH competitive antagonists) and inhibitors of α-MSH expression/generation A combination of one or more polypeptides, or both one or more polypeptides of an MCl-R antagonist (i.e. α-MSH competitive antagonist) and one or more polypeptides of a tyrosinase inhibitor A combination, or one or more polypeptides of an MCl-R antagonist (i.e., an α-MSH competitive antagonist), one or more polypeptides of a tyrosinase inhibitor, and one or more polypeptides that inhibit α-MSH expression/production or a combination of multiple peptides, the various types of peptides are as follows:

(1) One or more of the following polypeptides selected from MCl-R antagonists (ie α-MSH competitive antagonists), including but not limited to nonapeptide-1, hexapeptide-2;

(2), one or more of the following polypeptides selected from tyrosinase inhibitors, including but not limited to decapeptide-12;

(3), selected from one or more of the following polypeptides that inhibit the expression/production of α-MSH, including but not limited to tetrapeptide-27;

Wherein the mass concentration of the above polypeptide components is 0.0001%-5%.

2. according to the composition described in claim 1, it is characterized in that, described polypeptide composition can be nonapeptide-1 and tetrapeptide-27 combination, nonapeptide-1 and decapeptide-12 combination, nonapeptide-1 and A combination of hexapeptide-2; or a combination of nonapeptide-1, tetrapeptide-27 and decapeptide-12; or a combination of nonapeptide-1, tetrapeptide-27, hexapeptide-2 and decapeptide-12; each The mass concentration of the polypeptide component is 0.0001%-5%.

3. The composition according to claim 1, characterized in that, some polypeptides that inhibit tyrosinase gene expression can be added, such as oligopeptide-68, and the mass concentration of the polypeptide components is 0.001%-5%; or one or Several other components of tyrosinase inhibitors, such as phenylethylresorcinol, arbutin, kojic acid, and vitamin C derivatives, have their respective mass concentrations ranging from 0.001% to 5%.

4. Composition according to any one of claims 1 to 2, characterized in that an additional skin care active substance may be added in a mass concentration range of 0.001% to 5%, said active substance being selected from the group consisting of extracts Lipids and/or synthetic lipids, gelling and viscous, surface-active and emulsifying polymers, water- or fat-soluble active ingredients, plant extracts, tissue extracts, marine extracts, synthetic products, Sunscreens, antioxidants, moisturizers and sunscreens and/or skin rejuvenating actives.

5. By the composition of any one of claims 1 to 2, it is characterized in that a moisturizing agent can be added, the mass concentration range is 0.001%-5%, such as glycerin, aloe gel, hyaluronic acid, preferably hyaluronic acid acids; polyol preservatives, preferably caprylyl glycol.

6. The composition according to any one of claims 1 to 2, characterized in that it includes a comprehensive reagent for maintaining the stability of the antibacterial components, and the mass concentration range is 0.001%-5%, preferably 1,2-hexane diol.

7. The composition according to any one of claims 1 to 6, characterized in that it also includes a pH regulator selected from triethanolamine, sodium bicarbonate, potassium bicarbonate; preferably triethanolamine; the pH range of the composition 3.0 to 8.0, preferably 5.0 to 7.0.

8. The composition according to any one of claims 1 to 6, wherein the dosage form of the composition includes but not limited to essence, powder (capsule, lyophilized powder), emulsion, cream, gel, etc. Gels, masks, dressings.

9. The composition according to any one of claims 1-6, characterized in that, the composition products include but not limited to whitening and freckle mask, whitening and moisturizing essence, eye or face freckle essence, whitening cream , Medical dressings.

10. The composition according to any one of claims 1-6, characterized in that the composition is mainly used to prepare skin care products and medical products for external use on the skin.