KR101621061B1 - Compositions for antioxidation or improvement of skin conditions comprising curcumin-hexapeptide complexes - Google Patents

Abstract

The present invention relates to a composition for improving antioxidant or skin conditions comprising curcumin-hexa peptide complex as an active ingredient. The composition of the present invention can exhibit very good antioxidation and skin condition improving activity due to the synergistic effect between curcumin and the functional peptide. The composition of the present invention can be usefully used for the purpose of antioxidation, skin wrinkle improvement, skin elasticity improvement and skin aging prevention.

Description

TECHNICAL FIELD The present invention relates to a composition for curative antioxidation or improvement of skin condition comprising curcumin-hexapeptide complex,

The present invention relates to a composition for improving antioxidant or skin conditions comprising curcumin-hexa peptide complex as an active ingredient.

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 function to maintain beauty, but also protect skin, clean, moisturize, It should also have biological functions.

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 adults and children than in adults. For this reason, in the cosmetics and bio industry, various researches for the research and development and commercialization of high-functional cosmetics that maintain, enhance or restore the skin's health and improve or mitigate various skin diseases in the classical cosmetic function that protects and nourishes the beauty of the skin It is actively proceeding. In particular, the development of biotechnology has enabled 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-function semi-therapeutic cosmetics Is expected to surge.

As the national income increases, consumers' interest in health is increasing. In particular, interest in anti - aging and whitening is of great interest not only to 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. Particularly, in Korea, the Cosmetic Functional Law is enacted, and the function of the cosmetic is merely one step further in the role of skin protection or moisturizing, whitening (Patent No. 10-1257641, No. 10-1251040), Wrinkle prevention , Registered trademark 10-0890492, and registered trademark 10-0628518) have been actively developed.

A peptide material is one of the high-functional biomaterials that have recently been in compliance with this trend. Peptide production and application technology did not increase the specific synthetic technical altitude after the development of the solid phase peptide synthesis technique in the 1970s. However, since the sequence and structure of the amino acid sequence in the peptide have physiological activity in vivo or in the skin, (Patent No. 10-1527280, Patent No. 10-1410589) and pharmaceutical material (Patent No. 10-1375026, Patent No. 10-1437599).

Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to better understand the state of the art to which the present invention pertains and the content of the present invention.

Under these circumstances , the inventors of the present invention found that curcumin-hexapeptide fusion (a fusion of curcumin, a natural antioxidant component mainly present in Curcuma longa and acetyl hexapeptide-3 (argireline) The present inventors have developed a new material and confirmed synergistic skin physiological activity and confirmed that the external preparation for skin containing the same is very effective for improving wrinkles in particular.

Accordingly, an object of the present invention is to provide a cosmetic composition for improving antioxidant or skin condition.

Another object of the present invention is to provide a pharmaceutical composition for antioxidant or skin condition improvement.

Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.

According to one aspect of the present invention, the present invention provides a composition comprising curcumin; And a hexapeptide of the first sequence of SEQ ID NO: 1, which is bound to the N-terminal through the linker compound with the curcumin, wherein the C-terminal of the hexapeptide is acetamide, and the curcumin-hexapeptide complex is contained as an active ingredient And to provide an antioxidant or skin condition improving cosmetic composition.

According to another aspect of the present invention, the present invention provides a composition comprising curcumin; And a hexapeptide of the first sequence of SEQ ID NO: 1, which is bound to the N-terminal through the linker compound with the curcumin, wherein the C-terminal of the hexapeptide is acetamide, and the curcumin-hexapeptide complex is contained as an active ingredient And a pharmaceutical composition for improving the antioxidant or skin condition.

The present inventors have developed a curcumin-hexapeptide fusion new material which is a fusion of curcumin, a natural antioxidant component mainly present in Curcuma longa , and acetyl hexapeptide-3 (argireline), which is a functional peptide effective for improving wrinkles And its synergistic skin physiological activity was confirmed, and it was confirmed that the external preparation for skin containing the same was very effective for improving wrinkles in particular, thereby completing the present invention.

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).

The term "hexa-peptide" or "functional peptide" as used herein has an anti-wrinkle activity, the amino acid sequence of Glu-Glu-Met-Gln- Arg-Arg-NH 2 ( SEQ ID NO: 1, the C- terminal acetamide Amide). ≪ / RTI > If the N- terminus of SEQ ID NO hexapeptide of claim 1 having the sequence acetyl known as (Ac-Glu-Glu-Met -Gln-Arg-Arg-NH 2), azido relrin (Argireline, acetyl hexapeptide-3) Anti-wrinkle Functional peptide.

The curcumin-hexapeptide complex, which is an active ingredient contained in the composition of the present invention, includes the curcumin, the hexapeptide, and the linker compound 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-hexapeptide complex by covalently bonding to the N-terminus of the curcumin functional group (e.g., OH group) and the hexapeptide, respectively.

According to one embodiment of the present invention, the linker compound is bound by an ester linkage with curcumin and by a peptide linkage with a hexapeptide linkage. For example, when glutarate is used as the linker compound, the linker compound is bound to the OH group of curcumin by a condensation reaction (ester bond), and is bound (peptide bond) to the N-terminus of the hexapeptide by a condensation reaction A curcumin-hexapeptide complex is formed. The formula of the curcumin-hexapeptide complex is shown in FIG.

According to one embodiment of the present invention, the skin condition improvement is skin wrinkle improvement, skin elasticity improvement or skin aging prevention. As shown in the following examples, the curcumin-hexapeptide complex does not exhibit cytotoxicity (see FIG. 3), exhibits a strong antioxidative activity equivalent to that of vitamin C (see FIGS. 4 and 5), inhibits intracellular lipid peroxidation To prevent aging (see FIG. 6), and can greatly promote collagen biosynthesis (see FIG. 7). In particular, the cosmetic composition (external preparation for skin) comprising the curcumin-hexapeptide complex of the present invention can exhibit superior efficacy in improving wrinkles (see Tables 7 to 10).

The components contained in the cosmetic composition of the present invention include components commonly used in cosmetic compositions in addition to the curcumin-peptide complex as an active ingredient, and include conventional additives such as antioxidants, stabilizers, solubilizers, vitamins, , And a carrier.

The cosmetic composition of the present invention can be prepared into any of the formulations conventionally produced in the art and can be used as a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, , Oil, powder foundation, emulsion foundation, wax foundation and spray, but is not limited thereto. More specifically, it can be manufactured into a formulation of lotion (convergent lotion, soft lotion, etc.), cream, lotion, serum, essence, nutritional gel or massage cream.

When the formulation of the present invention is a paste, cream or gel, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .

In the case where the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. Especially, in the case of a spray, a mixture of chlorofluorohydrocarbons, propane / Propane or dimethyl ether.

When the formulation of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.

In the case where the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.

When the formulation of the present invention is an interfacial active agent-containing cleansing, the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, or ethoxylated glycerol fatty acid esters.

Meanwhile, when the composition of the present invention is manufactured from a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. The pharmaceutically acceptable carriers to be contained in the pharmaceutical composition of the present invention are those conventionally used in the formulation and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, But are not limited to, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrups, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. It is not. The pharmaceutical composition of the present invention may further contain a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).

The pharmaceutical composition of the present invention can be administered orally or parenterally, and in the case of parenteral administration, it can be administered by intravenous injection, subcutaneous injection, muscle injection, intraperitoneal injection, transdermal administration or the like. According to one embodiment of the invention, the pharmaceutical composition of the present invention is administered transdermally.

The appropriate dosage of the pharmaceutical composition of the present invention may vary depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate, . The dosage of the pharmaceutical composition of the present invention is within the range of 0.0001-100 mg / kg on an adult basis.

The pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container. The formulations may be in the form of solutions, suspensions, syrups or emulsions in oils or aqueous media, or in the form of excipients, powders, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.

The features and advantages of the present invention are summarized as follows:

(i) The present invention provides a composition comprising a curcumin-functional hexapeptide fusion-enhancing material.

(ii) The composition of the present invention can exhibit excellent antioxidation and skin condition improving activity simultaneously due to the synergistic effect between curcumin and the functional peptide.

(iii) The composition of the present invention can be usefully used for the purpose of antioxidation, skin wrinkle improvement, skin elasticity improvement and skin aging prevention.

Figure 1 shows the chromatographic results of the curcumin-hexapeptide complex produced through the purification process of the present invention.
Figure 2 shows a schematic synthesis process of a curcumin-hexapeptide complex.
3 shows the skin cell safety test results of the curcumin-hexapeptide complex. The safety of skin cells was tested by MTT assay, and the concentration was diluted 2 times at a maximum of 100 μM to a minimum of 6.25 μM. A: keratinocyte, B: fibroblast.
Fig. 4 shows the antioxidative effect of vitamin and curcumin. A: Vitamin, B: Curcumin.
Figure 5 shows the antioxidant effect of the curcumin-hexapeptide complex.
Figure 6 shows the lipid peroxidation inhibitory activity of the curcumin-hexa peptide complex.
Figure 7 shows the effect of promoting collagen biosynthesis of the curcumin-hexapeptide complex.

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 describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .

Throughout this specification, the term "%" used hereinbelow refers to the concentration of a specific substance. Solid / solid (weight / weight)%, solid / liquid (weight / The liquid / liquid is (vol / vol)%.

Example

Production example. Preparation of Curcumin-Hexapeptide Complex Using Ultrasonic Synthesizer

Raw materials used

Materials such as Fmoc-Glu (tbu) -OH, Fmoc-Met-OH, Fmoc-Gln (Trt) -OH and Fmoc-Arg (Pbf) -OH were purchased from GLS, curcumin purchased from TCI, The rate was purchased from Sigma, and the raw materials (DMF, DIEA, NMP, DCM) were purchased from purified gold.

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 amino acid sequence of Sequence Listing Sequence 1 by sequential 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 ° C.

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-hexapeptide complex

NH ₂ (amide resin) was swelled in a DMF solvent for 1 hour. Fmoc was then washed with 20% piperidine twice for 10 minutes, and then washed with DMF for 6 minutes for 6 times. Fmoc-Arg (pbf) -OH was completely dissolved in DMF in the amide resin and then put into the 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. Then, Fmoc-Arg (pBf) -OH, Fmoc-Gln (Trt) -OH, Fmoc-Met-OH, Fmoc-Glu Lt; / RTI > amino acid. 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-fabricating high-capacity ultrasonic synthesizer using DIEA. The reaction was carried out at a temperature of 35 ° C. 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 using a 70% TFA / DCM solution for 2 hours. The obtained crude product was purified by HPLC to obtain a curcumin-hexapeptide (Argireline) material. The specific synthesis process was as follows.

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 (dia 5 cm))

B. Composition of solvent: Buffer A = 0.1% TFA / acetonitrile, buffer B = 0.1% TFA / H ₂ O

C. Flow rate: 50-140 ml / min

D. Column: Silicagel C18 reverse phase

E. Gradient Table

On the basis of the results obtained from the synthesis of the medium scale (10 mmole) peptide, large-scale (100 mmole) synthesis of the peptide drug substance was performed and the scale-up was carried out. The synthesized crude peptide was purified by HPLC purification conditions to produce the final product (FIG. 1). A schematic synthesis process of the curcumin-azirrelin complex and its formula is shown in Fig.

Example 1. Human skin cell safety test of curcumin-hexapeptide complex

The MTT assay was performed to examine the presence or absence of safety or cytotoxicity of HaCaT cell line and CCD-986sk, which are cell lines for keratinocyte and fibroblast, against the curcumin-azirrelin complex. Respectively. For this, human keratinocyte HaCaT cells and fibroblast CCD-986sk were counted in a 24-well plate using 5 × 10 ³ cells / well and 5 × 10 ⁴ cells / well using a hemocytometer, Lt; / RTI > After culturing for 48 hours in DMEM containing 10% FBS and culturing to 50% of the culture vessel surface area, the culture was further cultured for 24 hours in a medium containing an appropriate concentration of curcumin-azirrelin complex. After incubation, 50 μl of MTT (3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide, Sigma M5655) solution (2.5 mg / ml) was added and further cultured for 3 hours. Then, 200 μl of dimethyl sulfoxide (DMSO, Sigma D2650) was treated with 200 μl of each well, and then 100 μl of each was taken at 96 wells, followed by enzyme-linked immunosorbent assay (ELISA) at 570 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 shown in Figure 3, the curcumin-azirrelin complex was not cytotoxic up to a treatment concentration of 100 [mu] M. In particular, fibroblasts showed about 20% cell proliferative activity at 50 μM of the curcumin-azirrelin complex, which promotes the proliferation of fibroblasts producing skin collagen without cytotoxicity as a cosmetic raw material, (FIG. 3B).

Example 2. Antioxidant test of curcumin-hexapeptide complex

A reactive oxygen species (ROS), also called a toxic oxygen species, is a toxic substance produced by cells due to physiological actions such as respiration and is produced and extinguished in a continuous state. do. These reactive oxygen species are free radicals such as superoxide radicals (O ^{2 -} ) and hydroxyl radicals (HO ⁺ ), which are not chemically coupled to the outermost electron orbit (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. Research on antioxidants capable of inhibiting oxidation by active oxygen has been actively carried out 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 DPPH (1,1-Diphenyl-2-picryhydrazyl, Sigma D9132-1G) on ethanol. Compound DPPH generates free radicals in ethanol, and it was mixed with a certain concentration of the sample, and the amount of free radicals was reduced to some extent. Specifically, 0.5 ml of a 0.1 mM DPPH solution and 0.1 ml of an extract diluted to a predetermined concentration were added to 0.4 ml of ethanol, vortexed vigorously for 10 seconds, and reacted in a dark place for 30 minutes. Absorbance was measured at 517 nm using ELISA and the degree of antioxidant activity was expressed as a percentage based on the absorbance of the ethanol-based control (negative control).

[Equation 1]

Free radical activity inhibition rate (%) = 100 - {(Reactive absorbance of each sample liquid / Reactive absorbance of the blank) X 100}

The antioxidant test of the curcumin-azirrelin complex was confirmed by the DPPH test. As a result, when curcumin was compared with vitamins, curcumin showed antioxidative effects similar to those of vitamins (FIG. 4). The curcumin-azirrelin complex also has a very good antioxidant activity against the control (FIG. 5). In the case of the curcumin-azirrelin complex, it reached a peak at 50 [mu] M, confirming synergy (Fig. 5). These results indicate that they have a similar antioxidant power to vitamin C, but are stable to skin cells and thus highly valuable as anti-aging cosmetic ingredients.

Example 3. Lipid peroxidation test method

Lipid peroxidation is well known as a mechanism of cell damage in animals and plants. Therefore, this lipid peroxidation was tested using a TBARS (Thiobarbituric Acid Reactive Substance) kit. Lipid peroxidation is an indicator of oxidative stress in the cell, which degrades to form more complex and reactive substances such as MDA or 4-HNE (4-hydorxynonenal), the two natural products of lipid peroxidation. The TBARS kit directly measures MDA (Malondialdehyde). As a specific experimental method, a human keratinocyte cell line was treated with an appropriate concentration of curcumin-azirrelin complex, and the culture was obtained and used. The test method was as follows. 100 μl of sample and MDA standard were dispensed into the E-tube and 100 μl of SDS lysis solution was added. After light mixing, the reaction was allowed to proceed at room temperature for 5 minutes, 250 μl of TBA reagent was added to each well, the lid of the E-tube was closed, and the reaction was allowed to proceed at 95 ° C for 45-60 minutes. After the reaction was completed, the mixture was further reacted on ice for 5 minutes, centrifuged at 3,000 rpm for 15 minutes, and the supernatant was analyzed. 200 [mu] l was transferred to 96 wells and read at 532 nm.

Intracellular lipid peroxidation is a direct cause of cell damage. Therefore, inhibiting intracellular lipid peroxidation means reducing cell damage and protecting against aging or disease. Experiments on the lipid peroxidation of the curcumin-azirrelin complex showed that the lipid peroxidation was reduced by about 20% or more when 100 μM of curcumin-azirrelin was treated (FIG. 6).

Example 4. Confirmation of collagen biosynthesis improvement of curcumin-hexapeptide complex

The various collagens secreted by fibroblasts that make up human skin are closely related to the aging process and wrinkle formation. 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 (Procollagen type I C-peptide) was used to compare the degree of increase of intracellular collagen production by treatment with 25 μM of curcumin-peptide complex when cultured human fibroblast Precoated, Takara Biomedical Co.). As a positive control for wrinkle-improving physiological activity, we evaluated whether the collagen biosynthesis promoting effect of retinol was 30% or more than that of retinol by using the wrinkle-improving functional retinol from Korea Food and Drug Administration (KFDA).

The collagen biosynthesis of the curcumin-azirrelin complex was measured by an ELISA kit, and it was confirmed that the curcumin-azirrelin complex promoted collagen biosynthesis in about 30% or more of the control group (FIG. 7).

Example  5. Curcumin - Hexapeptide  Complex-containing Cosmetics  Evaluation of efficacy of composition

In order to confirm the efficacy of the composition containing the curcumin-azirrelin complex in which the skin physiological activity has been confirmed by the above-mentioned experiments, lotion (Table 3), lotion (Table 4), cream ) And essence (Table 6) were applied 0.5% (5 g / kg) of curcumin-azirrelin complex. The manufacturing method of each formulation was as follows. To prepare the lotion, components 2, 3, 4 and 8 were added in order to component 11 of Table 1 and dissolved by stirring (lysate 1). 5 was dissolved by heating at about 60 ° C, and 10 times of the solution was dissolved therein (Lysate 2). The melt 2 was introduced into the melt 1. Finally, 1, 6, 7 and 9 were added and agitated after sufficient stirring.

Ingredients 10, 11, 13 and 16 in Table 2 were heated at 80-85 DEG C while mixing and stirring to put them in the manufacturing section and then emulsified to obtain 2, 3, 4, 5, 6, 7, 8, 9 and 12 were melted by heating at 80-85 DEG C and then emulsified. After completion of the emulsification, the mixture was cooled to 50 캜 with stirring using an agitator, and then the mixture was cooled to 45 캜 and then added at a temperature of 35 캜. The mixture was cooled to 25 캜 and aged.

To prepare the cream, ingredients 12, 13, 14 and 16 of Table 3 were heated at 80-85 DEG C while being mixed and stirred, put into a manufacturing part, emulsified, and then emulsified at 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11 were melted by heating at 80-85 DEG C, and then 15 parts were added and stirred. Then, the resultant was put into a manufacturing part and emulsified. After completion of the emulsification, the mixture was cooled to 35 DEG C with stirring using an agitator, and the mixture was cooled to 25 DEG C by the addition of No. 1, followed by aging.

To prepare the essence, Components 2, 3, 4, 5 and 6 of Table 4 were homogenized at a constant temperature to obtain nonionic amphipathic lipids. The non-ionic amphiphilic lipids 1, 7, 8, and 14 were mixed, homogenized at a constant temperature, passed through a microfluidizer, and then 9 was slowly added at a constant temperature to homogenize the microfluid. I passed it again. Then, 10, 11, 12 and 13 were added, dispersed, stabilized and aged.

In order to test the effect of wrinkle improvement on human skin with the prepared compositions, 16 healthy adult men and women over 50 years old were divided into two groups: compositions containing two kinds of curcumin-azirrelin complexes for 14 days and compositions The test was performed by applying 1 g (or ml) twice a day to the eye wrinkles. After 14 days of application, the improvement effect was evaluated by the satisfaction level of the degree of improvement of the wrinkles in the eyes.

number Raw material Content (% by weight) One Curcumin-azirrelin complex 0.5% 2 glycerin 3.0% 3 Butylene glycol 2.0% 4 Propylene glycol 2.0% 5 Polyoxyethylene hardened castor oil 1.0% 6 ethanol 10.0% 7 Triethanolamine 0.1% 8 antiseptic a very small amount 9 Pigment a very small amount 10 thurible a very small amount 11 Purified water up to 100%

number Raw material Content (% by weight) One Curcumin-azirrelin complex 0.5% 2 Wax 1.0% 3 Polysorbate 60 1.5% 4 Sorbitan sesquioleate 0.5% 5 Liquid paraffin 10.0% 6 Sorbitan stearate 1.0% 7 Pro-type glycerin monostearate 0.5% 8 Stearic acid 1.5% 9 Glyceryl stearate / FG-400 stearate 1.0% 10 Propylene glycol 3.0% 11 Carboxy polymer 0.1% 12 Triethanolamine 0.2% 13 antiseptic a very small amount 14 Pigment a very small amount 15 thurible a very small amount 16 Purified water up to 100%

number Raw material Content (% by weight) One Curcumin-azirrelin complex 0.5% 2 Stearic acid 2.0% 3 Cetyl alcohol 2.0% 4 Glyceryl monostearate 2.0% 5 Polyoxyethylene sorbitan monostearate 0.5% 6 Sorbitan sesquioleate 0.5% 7 Glyceryl monostearate / glyceryl stearate / polyoxyethylene stearate 1.0% 8 Wax 1.0% 9 Liquid paraffin 4.0% 10 Squalane 4.0% 11 Caprylic / capric triglyceride 4.0% 12 Carboxyvinyl polymer 0.3% 13 Butylene glycol 5.0% 14 glycerin 3.0% 15 Triethanolamine 0.5% 16 Purified water up to 100%

number Raw material Content (% by weight) One Curcumin-azirrelin complex 0.5% 2 Sitosterol 1.7% 3 Polyglyceryl 2-oleate 1.5% 4 Ceramide 0.7% 5 Steareth-4 1.2% 6 cholesterol 1.5% 7 Dicetyl phosphate 0.4% 8 Concentrated glycerin 5.0% 9 Macadamia oil 15.0% 10 Carboxyvinyl polymer 0.2% 11 Xanthan gum 0.2% 12 antiseptic a very small amount 13 Spices a very small amount 14 Purified water up to 100%

As a result, as shown in Tables 7 to 10, the wrinkle-improving effect was confirmed in the use groups of the composition containing the curcumin-azirrelin complex. Specifically, the compositions used as controls did not exhibit noticeable wrinkle-reducing effects, whereas compositions with curcumin-azirrelin complex 0.5% consistently exhibited wrinkle-improving effects. In particular, the percentage of respondents who said they were very effective in cream and essence formulations exceeded 50% of total use (Tables 7-10).

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

<110> AnyGen Co., Ltd.          BIO FD & C Co., Ltd. <120> Compositions comprising curcumin-hexapeptide complexes <130> PN130219 <160> 1 <170> Kopatentin 2.0 <210> 1 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> hexapeptide <400> 1 Glu Glu Met Gln Arg Arg   1 5

Claims (6)

Curcumin; And a hexapeptide of the first sequence of SEQ ID NO: 1 to which the N-terminal is bonded through the linker compound with curcumin, wherein the C-terminus of the hexapeptide is acetamide. Wherein the improvement of the skin condition is improvement of skin wrinkles or improvement of skin elasticity.
The cosmetic composition according to claim 1, wherein the linker compound is glutarate.
The cosmetic composition according to claim 1, wherein the linker compound is ester-bonded to curcumin and peptide-bonded to the N-terminal of hexapeptide.
delete The cosmetic composition according to claim 1, wherein the cosmetic composition is a formulation selected from the group consisting of lotion, cream, lotion, serum and essence.
delete

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