KR101733618B1 - Curcumin-tripeptide complexes and Anti-aging, Anti-oxidation, or Skin-improvement Composition for skin external application comprising the Same - Google Patents
Curcumin-tripeptide complexes and Anti-aging, Anti-oxidation, or Skin-improvement Composition for skin external application comprising the Same Download PDFInfo
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- KR101733618B1 KR101733618B1 KR1020150060177A KR20150060177A KR101733618B1 KR 101733618 B1 KR101733618 B1 KR 101733618B1 KR 1020150060177 A KR1020150060177 A KR 1020150060177A KR 20150060177 A KR20150060177 A KR 20150060177A KR 101733618 B1 KR101733618 B1 KR 101733618B1
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- curcumin
- skin
- tripeptide
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Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
- C07C49/255—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
Abstract
The present invention relates to a novel curcumin-tripeptide complex and an antioxidant and skin external composition for skin improvement comprising the same. More particularly, the present invention relates to a novel curcumin-tripeptide complex having excellent efficacy for wrinkle improvement and skin aging prevention, Skin improvement, and antioxidant skin external application composition.
The curcumin-tripeptide complex according to the present invention has antioxidant and collagen biosynthesis promoting ability, and has an excellent effect on skin wrinkle improvement and skin aging prevention.
Description
The present invention relates to a novel curcumin-tripeptide complex and an antioxidant and skin external composition for skin improvement comprising the same. More particularly, the present invention relates to a novel curcumin-tripeptide complex having excellent efficacy for wrinkle improvement and skin aging prevention, Skin improvement, and antioxidant skin external application composition.
The cosmetics industry is a technology-intensive, high-value-added industry in which basic science and applied technologies such as chemistry, biology, physiology, and pharmacy are applied in a technical aspect. Today, cosmetics are products that are directly used on human skin. They should have safety, efficacy and ease of use for skin. They should not only provide aesthetic functions to maintain beauty, but also to protect skin, clean, moisturize, It should also have the function. Due to changes in the living environment caused by the development of advanced industries, troublesome skin and skin diseases are increasing, and they are more severe in infants than adults. For this reason, in the cosmetics and bio industry, various efforts are being made to research, develop and commercialize highly functional cosmetics that maintain, enhance or restore the skin's health and induce improvement or mitigation of various skin diseases, in the classical cosmetic functions of protecting and nurturing the beauty of skin . In particular, the development of biotechnology enables the development and production of various physiologically active materials capable of satisfying the high level of functionality required along with the recent well-being culture, and the demand for high-performance semi-therapeutic cosmetics will surge . Especially, as the national income increases, consumers' interest in health is increasing. Particularly, interest in anti-aging and whitening is a major concern not only to many researchers but also to the general public. Although aging is a biological phenomenon commonly occurring in all the organs of the body, the appearance first appears on the skin, especially the skin. Therefore, many researches have been carried out in the field of cosmetics as well as biotechnology in order to delay or prevent such aging. Especially in Korea, the Cosmetic Functional Law is being implemented, and the function of cosmetics is one step further in the role of skin protection or moisturizing, and product development emphasizing functionalities such as whitening and wrinkle prevention is actively being carried out.
A peptide material is one of the high-functional biomaterials that have recently been in compliance with this trend. The development of such peptide materials has resulted not only in the import substitution effect in the high performance and high value added cosmetics market such as cosmetics and cosmeceuticals where almost all peptide derivative materials and products utilizing them are imported, It is possible to accumulate the technology for mass production of derivatives and it can be applied to the development of other biological materials in the future. In addition, it can be applied to the development of semi-therapeutic products for improving wrinkles, whitening, troublesome skin and skin diseases, and it is expected to have excellent industrial utility value.
In the case of curcumin, there is an example in which hexapeptide is conjugated to be used as a cosmetic composition or used for the purpose of treating eye diseases or skin diseases (Patent Document 1)
Our researchers have developed antioxidant and skin safety by developing a new material that combines curcumin and tripeptide (GHK), a powerful natural antioxidant found in Ulgum. Antioxidant ability was confirmed.
Accordingly, an object of the present invention is to provide a novel curcumin-tripeptide complex and a composition for external application for skin containing the same.
In order to accomplish the above object, the present invention provides a gene encoding a curcumin-tree, wherein the tripeptide having the amino acid sequence of GHK is bound to the N-terminus of curcumin through a linker compound, and the C- terminus of the GHK tripeptide is acetamide. Peptide complexes.
The present invention also provides an antioxidant or skin external composition for skin improvement comprising the curcumin-tripeptide complex as an active ingredient.
The term "1, 7-bis- (4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5-dione" is used herein to refer to turmeric ). ≪ / RTI > Curcumin can be obtained from a variety of sources, for example, chemically synthesized, and can be isolated from plants. For the purposes of the present invention, the curcumin also includes derivatives thereof which exhibit substantially the same activity as curcumin (for example, antioxidant ability).
As used herein, the term "tripeptide" or "functional peptide" refers to a tripeptide having wrinkle-reducing activity and having an amino acid sequence of Gly-His-Lys-NH2 (C-terminal acetamide).
The curcumin-tripeptide complexes according to the present invention include the above-mentioned curcumin, tripeptides, and linker compounds linking them. According to one embodiment of the present invention, the linker compound is a biodegradable linker compound. According to one particular example, the linker compound forms an ester bond with curcumin and can be hydrolyzed by an esterase in the body.
According to one embodiment of the present invention, the linker compound is glutarate. The glutarate linker can form a curcumin-tripeptide complex by covalently binding to the N-terminus of the curcumin functional group (e.g., OH group) and the tripeptide, respectively.
According to one embodiment of the present invention, the linker compound is bound to curcumin by an ester bond, and bound to a tripeptide by a peptide bond. For example, when glutarate is used as the linker compound, the linker compound binds to the OH group of curcumin by a condensation reaction (ester linkage), and binds (peptide bond) to the N-terminus of the tripeptide by a condensation reaction A curcumin-tripeptide complex is formed.
The synthesis process is schematically described as follows:
1. Curcumin-GHK synthesis
1) Trt resin swelling (Trt resin swelling)
- Swell rink amide resin (1.2 mmol / g) with a DMF (30 min)
- 2 washings of resin with DMF
2) Fmoc-Lys (boc) -OH loading (22 < 0 > C)
- Dissolve Fmoc-Lys (boc) -OH and DIEA in DMF
- The reaction time is 20 hours.
- Calculate substitution of loaded resin
3) Fmoc-His (trt) -OH coupling (22 < 0 > C)
- Remove Fmoc group of the resin using 20% piperidine / DMF solution
- 4 times resin wash with DMF
- Dissolve Fmoc-His (trt) -OH, HOBt, and DIC in DMF
- The reaction time is 4 hours.
4) Fmoc-Gly-OH coupling (24 ° C))
- Remove Fmoc group of the resin using 20% piperidine / DMF solution
- Resin cleaning with
- Dissolve Fmoc-Gly-OH, HOBt, and DIC in DMF
- The reaction time is 4 hours.
5) Glutaric anhydride coupling (23 ° C))
- Remove Fmoc group of the resin using 20% piperidine / DMF solution
- 4 times resin wash with DMF
- Dissolve Glutaric anhydride and DIEA in DMF
- The reaction time is 4 hours.
6) Curcumin coupling (23 ° C))
- 3 times resin wash with DMF
- Dissolve Curcumin, DMAP, and DIC in DMF
- The reaction time is 6 hours.
2. Cleavage
1) Resin react cleavage with solution of 70% TFA / 29% DCM / 1% H2O during for 3hr
2) Crystallize
3. HPLC purification
1) HPLC grade program: Acetonitile 30-40%, 10minute
2) Flow 14 ml / min, Absorbance 215 nm
4. Freeze-dried
5. Obtain final product
As shown in the following examples, the curcumin-tripeptide complex does not exhibit cytotoxicity, exhibits a strong antioxidative activity equivalent to that of vitamin C, inhibits cellular lipid peroxidation to prevent aging, highly promotes collagen biosynthesis . In particular, the cosmetic composition (external preparation for skin) comprising the curcumin-tripeptide complex of the present invention can exhibit superior efficacy in improving wrinkles.
In the present invention, the term "containing as an active ingredient" means a composition capable of exhibiting a whitening effect by reducing skin melanin synthesis and exhibiting collagen synthesis or antioxidative activity associated with wrinkle- ≪ / RTI > The content of the curcumin-tripeptide derivative in the composition is in the range of 0.1 to 10% by weight based on the whole composition.
In the present invention, the skin improvement includes the improvement of the skin condition, including the prevention of skin aging including the improvement of skin wrinkles, the improvement of elasticity, and the improvement of whitening function.
In the present invention, the composition for external application for skin may be a cosmetic composition or a pharmaceutical composition.
The cosmetic composition of the present invention may contain an acceptable carrier in cosmetic preparations. Herein, "an acceptable carrier for a cosmetic preparation" is a known or used compound or composition that can be contained in a cosmetic preparation, or a compound or composition to be developed in the future, which is toxic, instable or irritating It says nothing.
The carrier may be included in the skin topical composition of the present invention in an amount of from about 1% by weight to about 99.99% by weight, preferably from about 90% by weight to about 99.99% by weight of the composition, based on the total weight thereof. However, since the ratio varies depending on the formulations described below in which the composition for external application for skin of the present invention is prepared, and its specific application site (face, neck, etc.) or its preferable application amount and the like, And should not be construed as limiting the scope of the invention.
Examples of the carrier include an alcohol, an oil, a surfactant, a fatty acid, a silicone oil, a wetting agent, a moisturizer, a viscous modifier, an emulsifier, a stabilizer, an ultraviolet scattering agent, an ultraviolet absorber, a coloring agent and a perfume. It is possible to use the above alcohol, oil, surfactant, fatty acid, silicone oil, humectant, humectant, viscosifier, emulsion, stabilizer, ultraviolet scattering agent, ultraviolet absorber,
The compounds / compositions and the like that can be used are well known in the art, and those skilled in the art can select and use appropriate substances / compositions. In addition, conventionally known organic / inorganic UV blocking agents and natural products known to have ultraviolet shielding function may be additionally included.
In an embodiment of the present invention, the composition for external application for skin according to the present invention may contain glycerin, butylene glycol, propylene glycol, polyoxyethylene hardened castor oil, ethanol, triethanolamine and the like in addition to the tripeptide complex, , Antioxidants, coloring agents, purified water and the like may be included as needed.
The composition for external application for skin according to the present invention can be prepared in various forms such as lotion, essence, gel, emulsion, lotion, cream (underwater type, water type, multiphase), solution, suspension ), Capsules (soft capsules, hard capsules) having a coating such as anhydrous products (oil and glycol), gel, mask, pack, powder or gelatin.
The method for preparing the external composition for skin containing a tripeptide complex according to the present invention is not limited to the method disclosed in the embodiments, and any person skilled in the art may make modifications The composition for external application for skin containing the curcumin tripeptide complex according to the present invention can be prepared.
In particular, the composition for external application for skin may be prepared in the form of a general emulsified formulation and a solubilized formulation, by a known manufacturing method, in addition to the manufacturing method specifically disclosed in the present invention.
When the cosmetic composition is manufactured from a cosmetic composition, the cosmetic composition of the emulsified formulation includes nutritional lotion, cream, essence and the like. It can also be prepared in the form of adjuvants which can be applied topically or systemically, which are conventionally used in the field of dermatology by containing a dermatologically acceptable medium or base.
In addition, suitable cosmetic formulations include, for example, solutions, gels, solid or kneaded anhydrous products, emulsions obtained by dispersing an oil phase in water, suspensions, microemulsions, microcapsules, microgranules or ionic forms (liposomes) May be provided in the form of a follicular dispersing agent of the type, cream, skin, lotion, powder, ointment, spray or conical stick. It can also be prepared in the form of a foam or an aerosol composition further containing a compressed propellant.
In addition, the composition for external application for skin of the present invention may further comprise at least one selected from the group consisting of fatty substances, organic solvents, solubilizers, thickeners and gelling agents, softening agents, antioxidants, suspending agents, stabilizers, foaming agents, A lipid vesicle or a cosmetically active agent, a lipid vesicle or a cosmetically active agent, a lipid vesicle or a cosmetically active agent, a stabilizer, a stabilizer, Such as other ingredients of the cosmetic or dermatological science. And, the above ingredients can be introduced in amounts commonly used in the field of dermatology.
The composition for external application for skin according to the present invention includes functional cosmetics capable of antioxidant ability and antioxidant function according to collagen synthesis promoting ability.
Such a pharmaceutical composition may contain, in addition to the active ingredient, a "pharmaceutically acceptable carrier" which may be selected from the group consisting of diluents, lubricants, binders, disintegrants, sweeteners, stabilizers and preservatives. The pharmaceutical composition may further comprise an additive. The additives may include flavoring agents, vitamins, and antioxidants. Examples of the diluent include lactose, dextrin, tapioca starch, corn starch, soybean oil, microcrystalline cellulose or mannitol as a carrier, magnesium stearate or talc as a lubricant, , And the binding agent may be polyvinylpyrrolidone or hydroxypropylcellulose. Examples of the disintegrant include carboxymethylcellulose calcium, sodium starch glycolate, polacrilin potassium, or crospovidone; examples of sweeteners include white sugar, fructose, sorbitol, or aspartame; stabilizers include sodium carboxymethylcellulose, Or xanthan gum, and the preservative may be methyl paraoxybenzoate, propyl p-hydroxybenzoate, or potassium sorbate.
The pharmaceutical composition may be formulated into conventional pharmaceutical formulations known in the art. The pharmaceutical composition may be formulated and administered in the form of an oral administration preparation, an injection preparation, a suppository, a transdermal preparation, and a dosage form. For example, the formulations may be formulated for oral administration, such as solutions, suspensions, powders, granules, tablets, capsules, pills, or expanses.
Such a composition according to the present invention includes forms of functional cosmetics such as skin wrinkle improvement, anti-aging and the like.
The curcumin-tripeptide complex according to the present invention has a strong antioxidative ability and promoting collagen biosynthesis, and has excellent efficacy in the prevention of skin wrinkles and anti-aging.
FIG. 1 is a flow chart showing a process of synthesizing a curcumin-tripeptide complex according to the present invention.
Figure 2 shows the chemical structure of the curcumin-tripeptide complex of the present invention.
Figure 3 shows the HPLC purification results of the curcumin-tripeptide complex of the present invention.
Fig. 4 shows the results of skin cell safety test results of the curcumin-tripeptide complex. The safety of skin cells was tested by the MTT assay, and the concentration was diluted 2 times at a maximum of 100 M and treated to a minimum of 6.25 M. (A: keratinocyte, B: fibroblast).
Figure 5 shows the results of the antioxidant test effect of vitamin and curcumin. (A: vitamins, B: curcumin).
Figure 6 shows the results of the antioxidant test effect of the curcumin-tripeptide complex.
Figure 7 shows the lipid peroxidation inhibitory activity of the curcumin-tripeptide complex.
Fig. 8 shows the result of collagen biosynthesis test of the curcumin-tripeptide complex. (1: untreated test group, 2: curcumin alone treated group, 3: retinol treated group, 4: curcumin-tripeptide complex treated group).
FIG. 9 is a graph showing the wrinkle-improving ability of the curcumin-tripeptide complex. FIG.
Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for illustrating the present invention and that the scope of the present invention is not construed as being limited by these embodiments.
Preparation of novel curcumin-tripeptide complex
Raw materials used
Materials such as Fmoc-Gly-OH, Fmoc-His (trt) -OH and Fmoc-Lys (boc) -OH were purchased from GLS, curcumin was purchased from TCI, glutarate was purchased from Sigma, (DMF, DIEA, NMP, DCM) were purchased from purified water.
Fmoc deprotection
The deprotection of Fmoc was performed using 20% piperidine / DMF and washing was carried out for 5 minutes using DCM (Dichloromethane), DMF (dimethylformamide) and the like.
Amino acid bond
Amino acids were sequentially coupled to the GHK sequence by the solid phase synthesis method using HOBT / DIC (Hydroxybenzotriazole / diisopropylcarbodiimide) as a coupling reagent. The reaction time was 4 hours or more, and the synthesis temperature was 30.
Cleavage
After completion of the reaction, the total separation was carried out using a 70% TFA / DCM solution for 2 hours, extracted in ether and dried to obtain a non-purified peptide.
Synthesis of curcumin-tripeptide complex
The resin was swelled in a DMF solvent for 1 hour, then Fmoc was washed twice with 10% piperidine for 10 minutes and then washed with DMF for 6 minutes for 6 times. To the amide resin, Fmoc-Lys (boc) -OH was completely dissolved in DMF and then put into resin. HOBT and DIC were added as coupling reagents according to the equivalents of amino acids. Thereafter, synthesis was carried out for 4 hours or longer using an ultrasonic wave synthesizer (Sonicator, manufactured by Anisen).
When the reaction was completed, the solvent was vented and washed with clean DMF for 6 minutes for 2 minutes. Subsequently, coupling was performed with amino acids of Fmoc-His (trt) -OH and Fmoc-Gly-OH in the same manner as the above method. After washing, 3 equivalents of glutaric anhydride was added to the synthesized resin, and the reaction was carried out for 2 hours with a self-made high-capacity ultrasonic synthesizer using DIEA. Then, the above material was synthesized using 3 equivalents of DMAP and curcumin in the same manner as above. After completion of the synthesis, the mixture was separated for 2 hours using 70% TFA / DCM solution. The obtained crude product was purified by HPLC to obtain a curcumin-tripeptide (GHK) material.
The specific synthetic process conditions were as follows:
A. Resin substitution ratio: 1.2 mmol / g
B. Amino acids: Fmoc-Lys (Boc) -OH, Fmoc-His (trt) -OH, Fmoc-Gly-OH
C. Coupling Reagents: HOBt, DIC, DMAP
D. Coupling time: 4 hr
E. Coupling temperature: 30 DEG C
F. Isolation: 70% TFA in DCM
refine
The obtained peptide was purified by HPLC under gradient conditions under the following conditions and then lyophilized to obtain the desired peptide.
A. Instrument: Shimadzu 8A (5 cm * 25 cm) / 8 A (prep (
B. Composition of solvent: Buffer A = 0.1% TFA / acetonitrile, buffer B = 0.1% TFA / H2O
C. Flow rate: 14 / min
D. Column: Silicagel C18 reverse phase
E. Gradient: Acetonitile 30-40%, 10minute
Based on the results obtained from the synthesis of the medium scale (10 mmole) peptide, a large scale (100 mmole) synthesis of the peptide drug substance was carried out and scale-up was carried out. The synthesized crude peptide was purified by HPLC purification conditions to produce the final product (FIG. 3). The schematic synthesis process of the curcumin-GHK complex and its chemical formulas are shown in FIGS. 1 and 2.
Experimental Example 1: Cytotoxicity test of the curcumin-tripeptide complex
In order to examine the safety and cytotoxicity of HaCaT cell line and CCD-986sk, which are cell lines for keratinocyte and fibroblast, against curcumin-GHK, human skin constituent cells (keratinocyte and fibroblast) Respectively. For this, human horny cell line HaCaT cells and fibroblast CCD-986sk Cells were cultured in a 24-well plate at 5 × 10 3 cells / well and 5 × 10 4 cells / well using a heamacytometer and cultured for 48 hours in DMEM containing 10% FBS. To < RTI ID = 0.0 > 50%, < / RTI > cultured for 24 hours in medium containing curcumin-GHK complex at an appropriate concentration. After incubation, 50 μl of a solution of 2.5 mg / ml 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide (MTT, Sigma M5655, USA) was added and cultured for additional 3 hours. 100 μl aliquots were transferred into 96 wells and eluted with Enzyme-Linked Immunosorbent Assay (ELISA) at 570 cells / well. The cell lysates were discarded and 200 μl of dimethyl sulfoxide (DMSO, Sigma D2650, USA) nm absorbance was measured. The extent of promoting toxicity or proliferation to cells was expressed as a percentage based on the absorbance intensity of the control using pure water.
As a result, as shown in Fig. 4, it was confirmed that there was no cytotoxicity up to a treatment concentration of 100 uM and that cell proliferation was affected. In particular, fibroblast activated cell proliferation by about 60% or more compared to the control group, which means that it is highly effective in improving wrinkles.
Experimental Example 2: Antioxidant test of curcumin-tripeptide complex
A reactive oxygen species (ROS), also known as a toxic oxygen species, is a cell-generated toxic substance produced by physiological actions such as respiration and is constantly produced and extinguished, with 3-5% in normal conditions . These reactive oxygen species are free radicals such as superoxide radicals (O 2- ), hydroxyl radicals (HO + ), free radicals (such as atoms that are not paired chemically with the outermost electron orbits (Which is highly unstable and highly reactive with molecules) or in the form of compounds with paired electrons such as hydrogen peroxide (H 2 O 2 ) or singlet radical ( 1 O 2 ) exist. Active oxygen has the advantage of biologically protecting bacteria in the physiological system, but generally causes oxidation in vivo, causing harmful effects that cause disease. It is also reported that these reactive oxygen species attack biological molecules, damaging cells and tissues, and causing various diseases related to aging and diseases of various adult diseases. Studies on antioxidants capable of inhibiting oxidation by active oxygen have been actively conducted in the beauty industry, and research and development of natural materials and substances having strong antioxidant power have been attracting attention as anti-aging substances.
This test method can test the direct action of antioxidant effect on free radicals generated by 1,1-Diphenyl-2-picryhydrazyl (DPPH, Sigma D9132-1G) on ethanol.
[Equation 1]
Free radical activity inhibition (%) = 100 - {(Reactive absorbance of each sample liquid / Reaction absorbance of the blank) X100}
As a result, when curcumin, which is known to have antioxidant power, was compared with vitamins, curcumin showed similar antioxidative effects to vitamins (FIG. 5). Curcumin-GHK also has an antioxidant effect that is very superior to that of the control group (Fig. 6). This indicates that the antioxidant activity of curcumin-GHK is similar to that of vitamin C, while being stable to skin cells and highly valuable as an anti-aging cosmetic ingredient.
Experimental Example 3: Lipid peroxidation test of curcumin-tripeptide complex
Lipid peroxidation is well known as a mechanism of cell damage in animals and plants. In other words, intracellular lipid peroxidation is a direct cause of cell damage, and therefore inhibiting intracellular lipid peroxidation means reducing cell damage and protecting against aging or disease.
Lipid peroxidation test was conducted to confirm that the curcumin-tripeptide complex according to the present invention has the lipid peroxidation inhibiting ability. Specifically, it was tested using the Thiobarbituric Acid Reactive Substance (TBARS) kit (Oxiselect TBARS assay kit). Lipid peroxidate is an indicator of oxidative stress in cells and is degraded by forming more complex and reactive substances such as MDA or 4-hydorxynonenal (4-HNE), two natural products of lipid peroxidation. The TBARS kit is a technique for directly measuring malondialdehyde (MDA). As a specific experimental method, a suitable concentration of curcumin-Argireline was treated in a human keratinocyte cell line and the culture was obtained and used. The test method was as follows: 100 μl of sample and MDA standard were dispensed into E-tube and 100 μl of SDS Lysis solution was added. The mixture was lightly mixed and reacted at room temperature for 5 minutes. 250 ul of TBA reagent was added to each well, and the lid of the E-tube was closed and reacted at 95 ° C for 45-60 minutes. After the reaction was completed, the reaction was further added to ice for 5 minutes, centrifuged at 3,000 rpm for 15 minutes, and the supernatant was analyzed. Then, 200 ul of the supernatant was transferred to 96 wells and read at 532 nm.
As a result, it was confirmed that curcumin-GHK reduced lipid peroxidation by about 20% or more when treated with 100 uM (FIG. 7).
Experimental Example 4: Test for improving collagen biosynthesis of curcumin-tripeptide complex
The various collagens secreted by fibroblasts that make up human skin are closely related to the aging process and wrinkling. The anti-wrinkle activity of the test substance can be verified through the degree of collagen synthesis using fibroblasts. In order to confirm the degree of synthesis of collagen, procollagen type I C-peptide EIA Kit (Precoated, Korea) was used as a comparative test for the increase of intracellular collagen production by treatment with 25 uM of curcumin-GHK in human fibroblast (CCD986- Takara Biomedical Co.). As a positive control for wrinkle-improving physiological activity, KFDA assessed whether collagen biosynthesis is more effective than retinol, using retinol certified as wrinkle-reducing function.
As a result, as shown in Fig. 8, when the untreated control group was set as the reference (100%, test group 1), the curcumin treatment group was 68% (test group 2), the retinol treatment group ) Was 110% higher than that of untreated control group, while that of curcumin-GHK complex (test group 4) was increased about 134% as compared to untreated control group.
Experimental Example 5: Efficacy test of external preparation for skin containing curcumin-tripeptide complex
In order to confirm the efficacy of the composition containing curcumin-GHK, cosmetics were prepared by applying 100 ppm of curcumin-GHK to the formulation of Essence (Table 1) which is one of commonly used cosmetic formulations. The manufacturing method of this formulation is briefly as follows. To prepare the essence,
(100 ppm)
The results were as follows:
As a result of a human body test using a cosmetic composition containing 100 ppm (0.01%) of a curcumin-GHK peptide complex and a control composition containing no R-value, the results of Table 2 and FIG. As shown in Fig. 9, R1 of the parameters was significantly lower in the test group (p <0.05) than the control group at 12 weeks after using the product. In addition, it was confirmed that the skin adverse reaction was not observed in all the subjects who participated in the experiment and it was very safe.
The effect of reducing the wrinkles of the skin caused by curcumin-GHK was as shown in Table 2 above.
Preparation of cosmetic composition
Cosmetics such as lotion, cream, and the like were prepared with cosmetics containing the curcumin-tripeptide complex of the present invention as an active ingredient.
Production Example 2-1: Lotion
According to the following formulation, it was prepared according to the conventional lotion preparation method.
Production Example 2-2: Lotion
According to the following formulation, it was prepared according to a conventional lotion preparation method.
Production Example 2-3: Cream
According to the following formulation, it was prepared according to a conventional cream production method.
While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will appreciate that such specific embodiments are merely preferred embodiments and that the scope of the invention is not limited thereby. It will be obvious. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.
Claims (5)
Wherein the linker compound is glutarate,
The linker compound is ester-bonded to curcumin, peptide-bound to the N-terminus of the tripeptide,
Wherein the curcumin-tripeptide complex is contained at a concentration of 6.25 uM to 100 uM.
Wherein the linker compound is glutarate,
The linker compound is ester-bonded to curcumin, peptide-bound to the N-terminus of the tripeptide,
Wherein the curcumin-tripeptide complex is contained at a concentration of 100 ppm or less.
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