WO2017142158A1 - Composition for skin anti-aging and wrinkle reduction, containing medicinal herb mixture extract as active ingredient - Google Patents

Abstract

The present invention relates to a composition for skin wrinkle reduction and anti-aging, containing, as an active ingredient, a mixture of extracts of ginger, Atractylodes lancea, Curcuma longa and Cinnamomum cassia and, specifically, a mixture of extracts, obtained by mixing the extracts of ginger, Atractylodes lancea, Curcuma longa and Cinnamomum cassia in a ratio of 1 : 2.5-6.5 : 2.5-6.5 : 1 by weight, inhibits cell damage caused by UV radiation and remarkably inhibits the expression of MMP-1. The composition of the present invention can be used as cosmetics, dietary supplements and pharmaceutical compositions and, particularly, has a remarkable skin wrinkle reduction effect on soeum type among sasang constitutions classified in traditional Korean medicine.

Description

Composition for improving skin aging and wrinkles containing herbal extract as an active ingredient

The present invention relates to a composition for improving skin aging and wrinkles, which contains a herb extract as an active ingredient, and specifically, a ginger mixed with a weight ratio of 1: 3 to 6: 6 to 3: 1, creation, turmeric and broiler mixture. It relates to a skin aging and wrinkle improvement composition containing the extract as an active ingredient.

The skin protects the organs of the body from stimulation of the external environment and plays an important role in maintaining homeostasis such as temperature control. The skin is aged by various internal and external factors, and is classified into endogenous aging due to genetic causes and exogenous aging due to environmental causes. Among these, photoaging means aging by ultraviolet (UV). Recently, ozone layer destruction due to environmental pollution has increased the amount of ultraviolet rays, and thus, research on photoaging has been focused (Wang SQ et al., 2010, Dermatol. Ther. 23 (1): 31-47). In photo-aged skin, cosmetic features such as roughness, loss of elasticity, wrinkles and irregular pigmentation are observed. Among them, the main research field of photo-aging is about the change of skin wrinkles. A number of studies have been reported on basic physiological metabolic changes such as collagen, a major component of skin, and water content, regarding the formation of skin wrinkles by photoaging (Brenneisen et al., 2002, Ann.NY Acad. Sci., 973: 31-43). In particular, UV radiation increases the production of reactive oxygen species and disrupts the enzymatic and non-enzymatic antioxidant defenses of the skin, leading to increased collagen degradation and biosynthesis, which significantly reduces collagen in the dermal layer (Bickers DR , Athar M, 2006, J. Invest.Dermatol., 126 (12): 2565-2575). Significant effects on collagen reduction are collagen degrading enzymes (MMPs), which are involved in the degradation of extracellular matrix and basement membrane. It has been reported that the enzyme increases the activity by ultraviolet light and inhibits the increase in skin thickness and wrinkle formation induced by ultraviolet light (Inomata S et al., 2003, J. Invest. Dermatol., 120 (1): 128-134). Therefore, it is known to control MMPs for the prevention and treatment of photoaging.

On the other hand, ginger (Zingiber officinale) has been used as a food ingredient in the home because of its unique aroma and spicy, it is used a lot in all herbal prescriptions because of its various activities. The raw materials of Chinese herbal medicines are used in various ways. The harvested rhizome is called ginger, and the steamed or boiled ginger dried is called health (乾薑), and the roasted and dried is called black river. Ginger secretes digestive juices to promote appetite, promote gastrointestinal motility, aid in digestion and absorption, and is also used for asthma at the same time as it eliminates phlegm, lowers energy, stops vomiting, removes cold and boils (Clinical Traditional) Herbalogy, Younglimsa, 1997, 293-296; and above, Herbal Science, 1981, 203-204). It is also used for antipyretic drugs, blood circulation disorders, cold and cold. Aromatherapy ingredients increase blood circulation and body temperature, and take honey mixed with ginger juice to treat colds and coughs. On the other hand, health is used when metabolic function is lowered and is used as a treatment for cough, dizziness, cold hands and feet, low back pain, diarrhea and vomiting. It is also used for planting, boosting sheep and removing cold of five viscera.

In addition, Atractylodes lancea ) is a root stem in the genus (Compositae) and plant, which is distributed in North China, Shanxi, etc., and is irregularly bent cylindrical shape of 3 ~ 10cm long and 10 ~ 25mm in diameter, and the outer surface is made by dark ash. There is a point, pharmacological action is known to have a healthy, diuretic, sweating, sedative, hypoglycemic, tonic action. Creation is a perennial herb, which grows in mountains all over the country. In the fall, it is cut and washed in water to trim fine roots and to dry in the sun. There are about 1.5% essential oils, carotene, inulin, gum and alkaloid reactions, and outposts have saponin and coumarin reactions. It is sweet and spicy, warm and has sedation, hematopoiesis, and urinary action.In motion therapy, when the urine is low due to renal dysfunction caused by emphysema, gastroenteritis, swelling, dizziness and peeing when the whole body hurts, sweating medicine, etc. It is a very important medicine that is formulated in agreement.

Curcuma longa , also known as horseshoe turmeric, is cultivated in the sub-central part of Korea, and the roots are washed in water in autumn and boiled or steamed to dry. The taste is spicy, bitter and very warm. Promotes circulation and blood circulation, eliminates blood, eases pain and smoothes menstruation. In pharmacological experiments, it has been known that biliary tract function, liver detoxification function, analgesic action, uterine contraction action antibacterial action. It is used for amenorrhea, bleeding, and chest and stomach aches, swelling of arms, hepatitis, cholelithiasis, and bruising carbuncles.

In addition, broilers ( Cinnamomum cassia ) may have different plant origins and different qualities depending on the region. Since the sampling age and processing method differ from region to region, product specifications also include relatively many types such as variometers, relations, plates, chains, and chains. It is tubular or rolled into stem shell, 5 ~ 50cm long, 1.5 ~ 5cm in diameter, and 0.1 ~ 0.5cm thick. The outer side is dark reddish brown and the inner side is reddish brown and smooth. It is easy to bend and its face is reddish brown with a thin layer of light brown color and slightly fibrous. It has a peculiar smell, tastes slightly sweet and very, later slightly mucus and astringent.

On the other hand, ideology has been recognized through the four categories of personality, body type, physiology, pathology, mental psychology, and the entire universe through clinical observation. . In ideology, constitution is considered to be immutable once innate, and classified into four types of sun person, Taein person, Soyangin, and noise person according to the characteristics that determine characteristics, temperament, and personality aptitude. The disease can be prevented in advance, or when you get sick, depending on their constitution, the treatment is different. Therefore, even the same cosmetics, food or drugs may be beneficial or harmful depending on the constitution.

Among these Sasang constitution, the noise person is weak in spleen and stomach, and the kidney is faithful, so the shape of the body is well-balanced up and down. The woman is well-framed, dense, cute and charming. Forehead comes out a little, eyes, nose, mouth is not big, and the eyes are young and regular (이라 的) can be called. The skin is so soft and dense that there is little sweat, and a woman does not lose her hands even when working in winter.

Examples of known ginger, creation, turmeric and broiler mixed extract and skin wrinkle improvement or skin aging related technology cosmetic composition comprising a product dermis and ginger mixed extract having antioxidant and anti-aging effects in Korean Patent No. 1118765 And a method of manufacturing the same, a cosmetic composition for improving wrinkles is known from Korean Patent Publication No. 2008-0094457, and a cosmetic composition containing broiler extract is disclosed in Korean Patent Publication No. 2001-0055960. 0891986 discloses a herbal cosmetic composition containing a herbal extract and a herbal powder, but it is mentioned with respect to the cosmetic composition for skin wrinkle improvement and anti-aging containing the ginger, creation, turmeric and broiler mixed extract of the present invention as an active ingredient No bar

The present invention is derived from the above demands, ginger ( Zingiber officinale), Creation ( Atractylodes) lancea ), Curcuma Longa ) and Cinnamomum cassia ( Cinnamomum cassia ) relates to a composition for improving skin wrinkles and anti-aging containing the extract as an active ingredient, in particular ginger, creation, turmeric and broiler extract 1: 2.5 ~ 6.5: 2.5 ~ 6.5: 1 The mixed extract mixed in a weight ratio suppresses cellular damage by ultraviolet irradiation, significantly suppresses the expression of MMP-1, and in particular, confirms that there is an antiwrinkle effect on the noise person, thereby completing the present invention.

In order to achieve the above object, the present invention provides a cosmetic composition for skin wrinkle improvement and anti-aging containing ginger, creation, turmeric and broiler mixed extract as an active ingredient.

The present invention also provides a functional food composition for improving skin wrinkles and anti-aging containing ginger, creation, turmeric and broiler mixed extract as an active ingredient.

In another aspect, the present invention provides a pharmaceutical composition for preventing and treating skin wrinkles containing ginger, creation, turmeric and broiler mixed extract as an active ingredient.

The present invention relates to a composition for improving skin wrinkles and anti-aging containing ginger, creation, turmeric and broiler mixed extract as an active ingredient, in detail, the ginger, creation, turmeric and broiler extract 1: 2.5 ~ 6.5: 2.5 ~ 6.5 Mixed extracts mixed at a weight ratio of 1 to 1 inhibit cellular damage by UV irradiation and significantly inhibit the expression of MMP-1. When the blending ratio of ginger, crude, turmeric and broiler extracts is 1: 2.5 to 6.5: 2.5 to 6.5: 1 by weight, it is more effective to irradiate with ultraviolet rays than to mix with other blending ratios or to use ginger, crude, turmeric or broiler extracts alone. It suppresses cellular damage by and significantly suppresses the expression of MMP-1. The active ingredient of the present invention is effective to improve the skin wrinkles to the noise person in the Sasang constitution classified in the oriental medicine can be usefully used as a cosmetic composition, health functional food composition and pharmaceutical composition of the noise person.

1 is a concentration of each sample for 24 hours in HaCaT cells (human keratinocytes) in order to determine the cell survival rate by the mixing ratio (mixing according to the weight ratio) of ginger, creation, turmeric and broiler mixed extract of the present invention ( 50 μg / ml and 100 μg / ml), irradiated with ultraviolet (UV Crosslinker, UltR5 Lum) for 30 minutes, followed by an MTS assay.

Figure 2 is a result confirming the expression amount of MMP-1 by the mixing ratio (mixing according to the weight ratio) of the ginger, creation, turmeric and broiler mixed extract of the present invention.

3 is a definition and diagram of the wrinkle parameters used in replica analysis.

Figure 4 is a result of the analysis of the R1 parameter of the replica wrinkle effect between the test group and the control group using a product containing ginger, the production, turmeric and broiler mixed extract in a weight ratio of 1: 6: 3: 1 . (A) shows R1 values measured before use (0W), after 4 weeks of use (4W), after 8 weeks of use (8W) and after 12 weeks of use (12W). The change rate of R1 is shown based on the previous (0W). * Means that there is a statistically significant difference compared to before using the product according to the present invention (week 0), † means that there is a statistically significant difference between the test group and the control group, * And † indicate that the p value is less than 0.05.

Figure 5 is a result of the analysis of the R4 parameter of the replica wrinkle effect between the test group and the control group using a product containing ginger, the production, turmeric and broiler mixed extract in a weight ratio of 1: 6: 3: 1 . (A) shows R4 values measured before use (0W), after 4 weeks of use (4W), after 8 weeks of use (8W) and after 12 weeks of use (12W). The change rate of R4 is shown based on the previous (0W).

* Means that there is a statistically significant difference compared to before using the product according to the present invention (week 0), † means that there is a statistically significant difference between the test group and the control group, * And † indicate that the p value is less than 0.05.

The present invention relates to a cosmetic composition for improving skin wrinkles and anti-aging containing ginger, extract, turmeric and broiler mixed extract as an active ingredient.

The ginger, creation, turmeric and broiler extract is preferably extracted using at least one solvent selected from water, C ₁ ~ C ₄ lower alcohol, propylene glycol, ethyl acetate, butylene glycol, glycerin, ether and chloroform, more Preferably hot water extraction is not limited to this.

 The mixing ratio of the ginger, creation, turmeric and broiler extract is preferably 1: 2.5 to 6.5: 2.5 to 6.5: 1 weight ratio, more preferably 1: 2.5 to 3.5: 5.5 to 6.5: 1 or 1: 5.5 to 6.5 : 2.5 to 3.5: 1 by weight, most preferably 1: 5.5 to 6.5: 2.5 to 3.5: 1 by weight, but not limited thereto, and when mixed in the above 1: 2.5 to 6.5: 2.5 to 6.5: 1 weight ratio, The effect of improving wrinkles is superior to using alone or mixing in different weight ratios.

The cosmetic composition is characterized in that the noise is cited in the filamentous constitution, and whether or not the noise in the present invention is most preferably diagnosed by a medicinal doctor, the teacher is clinical character, body shape, physiology, pathology and mental psychology and According to the criteria classified as ideology, which is theorized by disease prevention, treatment and philosophy through the framework of four classifications (sun, lunar, literacy, noise) all over the universe, the noise person is short. He often walks in a poor and prone position, and his lower body is relatively developed, but overall he is dwarf, weak, and has a pretty face. Strongly feminine, calm, attentive, well cared for, thoughtful and prudent, but attentive and discreet, too timid, adventurous, and introverted , Selfishness and jealousy a lot, even small things are hurt and not easily released. Kidneys and bladder function is good, but the stomach is weak because it does not digest food well.

The cosmetic composition is effective in preventing skin aging and improving skin wrinkles by inhibiting the expression of MMP-1.

In the cosmetic composition according to an embodiment of the present invention, the skin wrinkle improvement and anti-aging cosmetic composition is an external skin ointment, cream, supple cosmetics, nourishing cosmetics, packs, essences, hair tonic, shampoo, conditioner, hair conditioner, hair Treatment, Gel, Skin Lotion, Skin Softener, Skin Toner, Astringent, Lotion, Milk Lotion, Moisture Lotion, Nutrition Lotion, Massage Cream, Nutrition Cream, Moisture Cream, Hand Cream, Foundation, Nutrition Essence, Sunscreen, Soap, Cleansing It may have any one formulation selected from the group consisting of foam, cleansing lotion, cleansing cream, body lotion and body cleanser, but is not limited thereto. The cosmetic composition consisting of each of these formulations may contain various bases and additives necessary for the formulation of the formulation and are suitable, and the type and amount of these components can be easily selected by those skilled in the art.

When the formulation of the cosmetic composition of the present invention is a paste, cream or gel, the carrier component is animal fiber, vegetable fiber, wax, paraffin, starch, tragacanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide. And the like can be used.

If the formulation of the cosmetic composition of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as the carrier component, and in particular, in the case of a spray, further chlorofluoro Propellants such as hydrocarbon, propane-butane or dimethyl ether.

When the formulation of the cosmetic composition of the present invention is a solution or emulsion, a solvent, solvating agent or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene. Fatty acid esters of glycol, 1,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan.

When the formulation of the cosmetic composition of the present invention is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Microcrystalline cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.

When the formulation of the cosmetic composition of the present invention is a surfactant-containing cleansing agent, the carrier component is an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, acethionate, an imidazolinium derivative, a methyltaurate, or a sarcosinate. Fatty acid amide ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.

The cosmetic composition of the present invention may further contain an excipient including a fluorescent substance, a fungicide, a caustic agent, a moisturizer, a fragrance, a fragrance carrier, a protein, a solubilizer, a sugar derivative, a sunscreen agent, a vitamin, a plant extract, and the like. .

In addition, the present invention relates to a functional food composition for skin wrinkle improvement and anti-aging containing ginger, creation, turmeric and broiler mixed extract as an active ingredient.

 The mixing ratio of the ginger, creation, turmeric and broiler extract is preferably 1: 2.5 to 6.5: 2.5 to 6.5: 1 weight ratio, more preferably 1: 2.5 to 3.5: 5.5 to 6.5: 1 or 1: 5.5 to 6.5 It is a weight ratio of 1: 2.5 to 3.5: 1, and most preferably 1: 5.5 to 6.5: 2.5 to 3.5: 1, but it is not limited thereto, and it is characterized by being a noise cited among filamentous constitutions.

When the health functional food composition of the present invention is used as a food additive, the health functional food composition may be added as it is or used with other foods or food ingredients, and may be appropriately used according to a conventional method. Mixed amounts of active ingredients may be suitably used depending on the purpose of use (prevention or improvement). In general, in the preparation of food or beverages, the nutraceutical composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less with respect to the raw material. However, in the case of long-term intake for health purposes, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.

There is no particular limitation on the type of dietary supplement. Examples of foods to which the health functional food composition may be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products, including ice cream, various soups, drinks, tea Drinks, alcoholic beverages, vitamin complexes, and the like, and include all health foods in the conventional sense.

In addition, the nutraceutical composition of the present invention may be prepared as a food, in particular a functional food. Functional foods of the present invention include ingredients that are commonly added in food production, and include, for example, proteins, carbohydrates, fats, nutrients and seasonings. For example, when prepared with a drink, natural carbohydrates or flavors may be included as additional ingredients in addition to the active ingredient. The natural carbohydrates may be monosaccharides (e.g. glucose, fructose, etc.), disaccharides (e.g. maltose, sucrose, etc.), oligosaccharides, polysaccharides (e.g., dextrins, cyclodextrins, etc.), or sugar alcohols ( For example, xylitol, sorbitol, erythritol and the like) are preferable. The flavourant may be a natural flavourant (eg, taumartin, stevia extract, etc.) and a synthetic flavourant (eg, saccharin, aspartame, etc.).

Various nutritional supplements, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonic acid The carbonation agent etc. which are used for a drink can be contained further. Although the ratio of the above-mentioned ingredients is not critical, it is generally selected from 0.01 to 0.1 parts by weight based on 100 parts by weight of the health functional food composition of the present invention.

In addition, the present invention relates to a pharmaceutical composition for preventing and treating skin wrinkles, which contains ginger, extract, turmeric and broiler mixed extract as active ingredients. The mixing ratio of the ginger, creation, turmeric and broiler extract is preferably 1: 2.5 to 6.5: 2.5 to 6.5: 1 weight ratio, but is not limited thereto, and is characterized by noise citation in filamentous constitution.

The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier in addition to the active ingredient, which is commonly used in the preparation of lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, Calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and minerals Oils and the like, but are not limited thereto. In addition to the above components, the pharmaceutical composition of the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences, 19th ed., 1995.

Suitable dosages of the pharmaceutical compositions according to the present invention vary depending on factors such as the formulation method, mode of administration, age, weight, sex, morbidity, food, time of administration, route of administration, rate of excretion and response to response of the patient. Can be. On the other hand, the dosage of the pharmaceutical composition of the present invention is preferably 0.0001 to 100 mg / kg (body weight) per day.

The pharmaceutical composition of the present invention can be administered orally or parenterally, and in the case of parenteral administration, it can be administered topically to the skin, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration and the like.

The concentration of the active ingredient included in the pharmaceutical composition of the present invention can be determined in consideration of the purpose of treatment, the condition of the patient, the period of time, etc., and is not limited to a specific range of concentration.

The pharmaceutical compositions of the present invention may be prepared in unit dosage form by formulating with a pharmaceutically acceptable carrier or excipient according to methods which can be easily carried out by those skilled in the art. It can be prepared by incorporation into a dose container. In this case, the formulation may be prepared in any one formulation selected from injections, creams, patches, sprays, ointments, warnings, lotions, linings, pastas and cataplasmas, and may further include a dispersant or stabilizer. Can be.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for explaining the present invention in more detail, it is obvious to those skilled in the art that the scope of the present invention is not limited by them.

[Materials and methods]

1. Preparation of Herbal Extracts

Herbal medicine was purchased from OmniHub, and each sample was stored in a herbal storage refrigerator maintaining a temperature of 5.5 ± 0.3 ℃ and humidity of 55 ± 5%. Ginger, creation, turmeric and broiler extracts were extracted by refluxing twice with reflux for 3 hours by adding water corresponding to 10 times the total weight of each of ginger, creation, turmeric and broilers. The extract was prepared by removing the solvent.

2. Cell experiment

1) Cell Culture

HaCaT cells (human keratinocyte line) were 10% fetal bovine serum (FBS, Gibco) and 1% penicillin-streptomycin (PS, Gibco) in Dulbecco's Modified Eagle Medium (DMEM, Gibco). The medium was incubated at 37 ℃, 5% CO ₂ conditions.

2) Cell survival rate analysis

Each sample was diluted with HaCaT cells (human keratinocyte cell line) for 24 hours, and irradiated with UV Crosslinker (Ultra Lum) for 30 minutes, followed by MTS assay (CellTiter Aqueous One Solution Cell proliferation assay kit, 3). -(4,5-dimethylthiazol-2-yl) -5- (3-carboxymethoxyphenyl) -2- (4-sulfophynyl) -2H-tetrazolium, inner salt; MTS, Promega Co. Madison, WI, USA) Viability was tested by measuring with a microplate reader (Molecular Devices, Sunnyvale, CA, USA) at 490 nm.

3) Expression level analysis of MMP-1

Each sample was treated with HaCaT cells (human keratinocyte cell line) for 24 hours and irradiated with UV crosslinker (Ultra Lum) at 20 mJ / cm ² , followed by MMP-1 ELISA kit (R & D Systems, Inc., Minneapolis, MN). , USA) was used to measure the expression level of MMP-1.

Specifically, after the HaCaT cells were plated in 96-well plates, ginger, extract, turmeric and broiler mixture extracts of the present invention were treated for various mixing ratios. Thereafter, ultraviolet (UV) irradiation, the supernatant of the culture was collected and centrifuged for 5 minutes at 13,000 rpm. Then, the supernatant was taken and subjected to fluorescence assay using an ELISA kit to quantitatively analyze the expression level of MMP-1.

3. Human application test

1) Test purpose

The purpose of this study is to evaluate the effect of wrinkle improvement and skin safety on 12 weeks of use of the test product for women whose wrinkles are starting to occur or who are already aged 30-65 years old. (Clinical Study No .: DEF-HSWIT001 ( 4) -14060).

2) test products

-Product Name: KIOM SY (2015SY 1-1)

Test group (A): 1.0% mixture of ginger extract (0.09g), extract extract (0.55g), turmeric extract (0.27g), broiler extract (0.09g)

-Control group (B): Ginger extract, creation extract, turmeric extract, broiler extract free

-Appearance of product: Cream

-Storage of the product: Store at room temperature

-Active ingredient of the product: 1.0% mixture of ginger extract (0.09g), extract extract (0.55g), turmeric extract (0.27g), broiler extract (0.09g)

-How to use: After washing twice a day for 12 weeks, skin A and B were applied to the left and right eye areas and absorbed after the next step. Subjects were divided into two groups according to the double-blind method and randomization. Group A had the test group (product A) on the left side and control group (product B) on the right side, and group B had the control group (product B) on the left side and the right side. A test group (product A) was used.

3) test method

All subjects were cleaned at each visit, and then placed in a constant temperature and humidity room (22 ± 2 ° C, 50 ± 5%) and rested for 30 minutes before participating in the test.

The evaluation is performed on the skin safety through visual evaluation, skin wrinkle parameter measurement, questionnaire evaluation by the subject and observation and questionnaire at each time before and after use of the product (week 0 and week 4, 8, 12). It was.

① Subject Selection

Constitution using the SCAT program (Korea Patent Publication No. 2012-0034475, JH DO. Et.al 2012, Development of an intefrated Sasang constitution diagnoisis method using face, body shape, voice, and questionnaire information 12:85) Screening was performed according to the identified clinical subject selection procedure.

The study recruited noisy women between the ages of 30 and 65 and recruited 22 noisy female subjects who met the subject selection criteria and did not meet the exclusion criteria. Their age ranged from 35 to 54 years (mean age: 45.2). ± 5.2 years old).

Skin wrinkles are tested by dermapro dermatological research institutes who have started to produce wrinkles or who have already participated in this study. A participation agreement was written and the participants participated in the test.

In addition, before the test, BMI measurement (Inbody 330, Biospace, Korea), body circumference measurement, photography and Sasang Constitution Diagnosis Questionnaire Evaluation were conducted to determine the noise factor. The noise factor was selected using (SCAT, Sasang Constitutional Analysis Tool).

-The primary filtering of the clinical subjects was carried out using 2-3 questions that can roughly classify the constitution.

-The constitution was diagnosed through SCAT in the first filtered subjects, and the constitution factor, which is the noise according to the present invention, was selected.

-22 patients who exceeded the skin clinical baseline of 20 were selected as the final clinical trial subjects.

The highest constitution value (max (TE, SE, SY)) and second highest constitution value (median (TE) SE, SY)) were selected in order of big difference, and 22 people (including one dropout) who were judged as noise noise were selected.

[Subject selection criteria]

Candidates who met the conditions as described below were selected as test subjects.

-A person who has wrinkles on the test site according to the judgment of the main investigator by the noise person (diagnosis by SCAT program) of 30 ~ 65 years old

-Healthy person without grade and chronic physical disease including skin disease

-Applicants who have fully explained the purpose and content of the examination prior to the examination and voluntarily signed the written consent.

-Those who can follow up during the test

[Subject exclusion criteria]

Applicants corresponding to the items listed below were excluded from the test group.

-If you are planning to become pregnant, during lactation or within 6 months

-If the skin steroid containing steroids is used for more than 1 month to treat skin disease

-6 months have passed since participating in the same exam

-If you have sensitive or sensitive skin

-If there are any abnormalities on the test site such as spots, acne, erythema, and capillary dilatation

-When the same or similar cosmetics or medicines are used at the test site within 3 months of starting the test

-If you have undergone a procedure (dermabrasion, botox, other skin care, etc.) at the test site or plan within 6 months

-Have chronic wasting diseases (asthma, diabetes, high blood pressure, etc.)

-If it is judged difficult by other principal investigator's judgment

 [Subject Restrictions]

Subjects should not mix with functional cosmetics or medicines other than the test product.The basic cosmetics used outside the test product are only skins and lotions without functional ingredients. Sun cream products should be used when going out. At the time of visit (measurement), the visit was made without color makeup.

[Number of subjects and the rationale for this]

The number of subjects was tested by selecting 20 or more subjects according to guidelines for evaluating the effectiveness of functional cosmetics (2003, 2005), and guidelines for test methods for cosmetic labeling and advertisement (2013).

② Visual evaluation of skin wrinkles

Visual evaluation was independently performed by two test subjects under certain illumination according to the wrinkle evaluation criteria for wrinkles of both eyes. For each evaluation time point, the grade of wrinkles was recorded in 10 steps (0.5 point units), and the average value of two testers was analyzed (Table 1).

Visual wrinkle criterion modified from Daniel's criteria

score	Wrinkle Evaluation Criteria
0	There are no wrinkles on the skin and the skin texture is delicate.
One	Shallow wrinkles begin to appear on the skin.
2	Shallow wrinkles appear on the skin.
3	Many wrinkles or normal wrinkles begin to appear.
4	Usually wrinkles appear on the skin.
5	It has normal wrinkles but no deep wrinkles.
6	Usually wrinkles or deep wrinkles begin to appear.
7	Deep wrinkles appear on the skin.
8	There are many deep wrinkles on the skin.
9	There are many deep wrinkles on the skin.

③ Evaluation of skin wrinkle parameter using replica

Skin wrinkles were evaluated by analyzing skin replica images using Visioline® VL650 (C + K, Germany) at each time point. When the device is irradiated with light, the intensity of transmitted light varies depending on the thickness of the replica according to the shape of the skin.

R1 is the difference between the highest peak and the lowest valley of the wrinkle profile, and R2 equals five wrinkle profiles to get five R1 values, which is the largest of them. . R3 is an arithmetic mean of five consecutive R1 values by equalizing five wrinkle profiles, resulting in the removal of artifacts compared to R1 and R2. R1, R2, and R3 can be understood as values representing the depth of wrinkles. R4 is the average depth of skin wrinkles by drawing the horizontal line at the top of the profile and integrating the area with the profile divided by the length of the midline of the profile. R5 is the mean roughness of the skin divided by the length of the midline of the profile by integrating the area between the midline of the profile and the profile (FIG. 3).

Based on this principle, there are three methods for measuring R1, R2, R3, R4, and R5: horizontal, vertical, and circular. Was measured in a circular manner.

④ Take a picture

At each evaluation point, facial left and right sides were photographed using a facial skin imaging device (VISIA® CR, Canfield, USA).

⑤ Survey evaluation by subject

The questionnaire about the efficacy of the product was conducted by the subject at the 4, 8, and 12 weeks of product use.The subjects were assessed at the 5-point scale (1, not at all; 2, not at all; 3. no difference; 5. Very much). In addition, the questionnaire on product usability was assessed on a five-level scale (1, not at all; 2, not good; 3, moderate; 4, good; 5, very good) at the time of evaluation 12 weeks after product use. The positive responses (4, good; 5, very good) written by the subjects were analyzed.

⑥ Skin safety assessment

Subjective skin irritation and objective skin irritation were assessed through questionnaires and observations at 4, 8 and 12 weeks after product use.

4) Statistical Analysis

All data were verified statistical significance using SPSS package program (IBM, USA) .In case of visual evaluation, intraclass correlation coefficient (ICC) analysis was performed by inter-tester reliability analysis. It was analyzed by applying the average value of the investigator. In addition, normality was verified by kurtosis and skewness, and prior homogeneity was verified by paired t-test.

Repeated Measures ANOVA was applied to identify interdependence (interaction), cross-group comparison, and before and after changes in time-point data in the same subject. The comparison between groups at each time point and the change before and after each time point were performed using the Mann-Whitney U-test under the condition that the values before and after the use of the product were used. The product usability questionnaire was analyzed using the Chi-Square test. . Each statistical significance level was considered to be significant that the p value is less than 0.05.

Example  Ginger, creation, curcuma  And a mixture of broiler extracts

As described in [Materials and Methods], ginger, creation, turmeric and broiler extracts were prepared, and the weight ratio of ginger: creation: turmeric: chicken was 1: 1: 1: 1, 1: 2: 2: 1,1 The mixed extracts were prepared by mixing 1: 3: 3: 1, 1: 3: 6: 1, 1: 6: 3: 1.

In the following examples, the cell viability and MMP-1 expression levels were analyzed using the mixed extract prepared in Example 1, and the most effective mixed extract was selected to analyze the wrinkle improvement effect on 21 people with noise.

Example  2. ginger, creation, curcuma  And cell for broiler mixed extract Survival rate  analysis

The weight ratio of 1: 1: 1: 1, 1: 2: 2: 1, 1: 3: 3: 1, 1: 3: 6: 1 and 1: 6: 3: 1 prepared in Example 1 The mixed ginger, extract, turmeric, and broiler mixed extracts were treated with HaCaT cells (human keratinocyte line) for 24 hours, irradiated with ultraviolet (UV Crosslinker, Ultra Lum) for 30 minutes, and then subjected to MTS assay. As shown in Figure 1, the cell survival rate was different according to the mixing ratio of the ginger, the production, turmeric and broiler mixture extract, the cell survival was reduced to 51.09% by UV irradiation, the mixing ratio 1: 6: 3: The cell survival rate was 74.85% when treated with 50 μg / ml of ginger, production, turmeric and broiler mixed extract of 1, and the cell survival rate was 80.99% when treated with 100 μg / ml. The cell survival rate was 93.93% when treated with ginger, production, turmeric and broiler extracts 3: 3: 1, and the cell viability was 94.11 when treated with 100 μg / ml. Appeared in%.

On the other hand, when the ginger, the production, turmeric and broiler extracts were treated alone, the cell survival rate was lower or almost similar to that of the UV irradiation alone.

Example 3 Effect of Ginger, Produced, Turmeric and Broiler Mixture Extracts on Expression of MMP- 1

Collagen degrading enzymes (MMPs) are enzymes that affect collagen reduction by being involved in the degradation of extracellular matrix and basement membrane.

In Example 3, the effect of improving wrinkles of a mixture of ginger, creation, turmeric and broiler extracts, which are active ingredients of the present invention, was analyzed by analyzing the change in the expression level of collagen degrading enzymes (MMPs; matrix metalloproteinases), which have a significant effect on collagen reduction Check whether there is.

As shown in FIG. 2, although the expression level of MMP-1 was very low in the cells not irradiated with ultraviolet rays, it was confirmed that the expression of MMP-1 was significantly increased by ultraviolet irradiation. In the case of treatment with the ratio of the production, turmeric and broiler extracts, the expression level (ng / ml) of MMP-1 was significantly reduced compared to the case of ultraviolet irradiation. In particular, when ginger, extract, turmeric and broiler extracts are mixed at a weight ratio of 1: 6: 3: 1, by confirming that the expression level of MMP-1 is very low, it is determined that the active ingredient of the present invention is effective in improving wrinkles. It was.

Example 4 Clinical Trials Using Test Products Containing Ginger, Produce, Turmeric, and Broiler Mixture Extracts Mixed in a Weight Ratio of 1: 6: 3: 1

In Example 4, based on the results of Examples 2 and 3, to prepare a test product containing a mixture of ginger, creation, turmeric and broiler mixed extract in a weight ratio of 1: 6: 3: 1, the most effective We conducted a clinical trial that applied it to 21 noisy patients.

In this test, 22 female subjects aged 30 to 65 who met the exclusion criteria and selection criteria participated, but one (# 8; individual) drop out and 21 subjects (mean 45.2 ± 5.2 years old) were completed. The whole process was faithfully carried out. The skin characteristics of the subjects were examined by questionnaire.

Group 21 is a test group containing ginger, extract, turmeric and broiler mixed extract of 1: 6: 3: 1, which is an active ingredient of the present invention, and group B is a control group that does not contain the active ingredient of the present invention. The group that used the product. Tables 2 to 4 below disclose information, skin types and skin conditions of test groups (A) and control groups (B) participating in clinical trials.

Information from test group (A) and control group (B) (N = 22)

NO	name	age	Classification by Sasang Constitution	group	Dropout
One	L * J	48	Noisemaker	A
2	O * S	48	Noisemaker	B
3	A * J	47	Noisemaker	B
4	I * E	39	Noisemaker	A
5	L * Y	48	Noisemaker	A
6	H * S	41	Noisemaker	A
7	K * J	50	Noisemaker	B
8	J * J	57	Noisemaker	B	personal issues
9	K * S	54	Noisemaker	A
10	L * S	45	Noisemaker	B
11	Y * S	50	Noisemaker	A
12	P * S	38	Noisemaker	B
13	K * J	36	Noisemaker	A
14	K * S	45	Noisemaker	B
15	Y * Y	35	Noisemaker	B
16	K * H	47	Noisemaker	A
17	K * J	45	Noisemaker	A
18	J * S	53	Noisemaker	B
19	J * S	41	Noisemaker	B
20	L * H	46	Noisemaker	A
21	K * S	49	Noisemaker	A
22	J * H	45	Noisemaker	A
Mean age ± standard deviation: 45.2 ± 5.2 years (excluding dropout subjects)

Skin type of test and control group (N = 21)

Item	Classification	Number of testers (N)	ratio(%)
Age	30 spaces	4	19.05
	40 spaces	13	61.90
	50 spaces	4	19.05
Skin type	inattention	10	47.62
	neutrality	6	28.57
	Intelligence	2	9.52
	Guernsey	3	14.29
	Problem skin	0	0.00

Skin condition of test and control groups (N = 21)

Item	Classification	Number of testers (N)	ratio(%)
Hydration		Moist	0	0.00
	usually	11	52.38
	lack	10	47.62
Oil	Bundle	One	4.76
	usually	11	52.38
	lack	9	42.86
Surface	Soft	5	23.81
	usually	13	61.90
	coarseness	3	1.29
Thickness	Thin	8	38.10
	usually	12	57.14
	Thick	One	4.76
Duration of UV exposure	in 1 hour	6	28.57
	1-3 hours	10	47.62
	More than 3 hours	5	23.81
Sleeping hours	5 hours or less	One	4.76
	5-8 hours	18	85.71
	More than 8 hours	2	9.52
Smoking	Do not smoke.	21	100.00
	Within 10 pieces	0	0.00
	More than 10	0	0.00
Irritability	Yes	3	14.29
	no	18	85.71
Stinging	Yes	2	9.52
	no	19	90.48
Adverse reaction	Yes	0	0.00
	no	21	100.00

1) Visual evaluation of skin wrinkles

In the present embodiment, as described above, the skin of the test group and the control group was visually analyzed using RM ANOVA before, after 4 weeks, after 8 weeks, and after 12 weeks of application.

As a result, the visual evaluation did not show a significant difference between the test group and the control group (Table 5).

Statistical significance (p value) for visual evaluation of test group (A) and control group (B) using a cream-type product containing ginger, crude, turmeric and broiler mixed extracts

Group comparison (N = 21)	4 Weeks	8 Weeks	12 Weeks
Test group vs. Control	-	-	0.329

2) Skin wrinkle parameter analysis using replica

The R1 and R4 parameters were found to be significantly improved in the test group compared to the control group at 12 weeks after product use (Table 6, Figures 4 and 5).

Statistical significance (p value) for replica analysis of test group (A) and control group (B) using a cream type product containing ginger, crude, turmeric and broiler mixed extracts

parameter	group	4 Weeks	8 Weeks	12 Weeks
R1	Test group vs. Control	0.262	0.259	0.000 *
R2	Test group vs. Control	0.275	0.085	0.215
R3	Test group vs. Control	0.410	0.623	0.149
R4	Test group vs. Control	0.104	0.110	0.024 *
R5	Test group vs. Control	0.148	0.077	0.052

*: p value is less than 0.05, which means that there is a significant difference between the test group and the control group.

3) Skin safety assessment

No skin adverse events were observed in all subjects during this study. Therefore, the active ingredient of the present invention was determined to have no toxicity or side effects (Table 7).

Evaluation of Skin Safety on Skin Adverse Events in Test Group (A) and Control Group (B) Using Cream-Type Products Containing Ginger, Produce, Turmeric and Broiler Mixture Extracts

Symptom		4 Weeks		8 Weeks		12 Weeks
		A	B	A	B	A	B
Subjective irritation		Itching	0	0	0	0	0	0
	Sick like a needle stab (Prickling)	0	0	0	0	0	0
	Tickling	0	0	0	0	0	0
	Burning (Burning)	0	0	0	0	0	0
	Stinging	0	0	0	0	0	0
	Stiffness	0	0	0	0	0	0
	Tightening	0	0	0	0	0	0
	Miscellaneous	0	0	0	0	0	0
Objective Irritation		Erythema	0	0	0	0	0	0
	Edema	0	0	0	0	0	0
	Scale	0	0	0	0	0	0
	Papule	0	0	0	0	0	0
	Miscellaneous	0	0	0	0	0	0
Total number of subjects		0	0	0	0	0	0

Claims (10)

1. A cosmetic composition for improving skin wrinkles and anti-aging, comprising ginger, extract, turmeric and broiler mixed extract as active ingredients.
2. The method of claim 1, wherein the ginger, extract, turmeric and broiler mixed extract using at least one solvent selected from water, C ₁ ~ C ₄ lower alcohol, propylene glycol, ethyl acetate, butylene glycol, glycerin, ether and chloroform Skin wrinkle improvement and anti-aging cosmetic composition, characterized in that extracted by.
3. According to claim 1, wherein the blending ratio of the ginger, creation, turmeric and broiler extract is 1: 2.5 to 6.5: 2.5 to 6.5: 1 weight ratio characterized in that the cosmetic composition for skin wrinkle improvement and anti-aging.
4. The cosmetic composition for improving skin wrinkles and anti-aging according to claim 1, wherein the cosmetic composition is used for noise in the filamentous constitution.
5. The cosmetic composition for improving skin wrinkles and anti-aging according to claim 1, wherein the cosmetic composition inhibits the expression of MMP-1.
6. According to claim 1, wherein the cosmetic composition is an external skin ointment, cream, supple cosmetics, nourishing cosmetics, pack, essence, hair tonic, shampoo, conditioner, hair conditioner, hair treatment, gel, skin lotion, skin softener, skin toner , Astringent, Lotion, Milk Lotion, Moisture Lotion, Nutrition Lotion, Massage Cream, Nutrition Cream, Moisture Cream, Hand Cream, Foundation, Nutrition Essence, Sunscreen, Soap, Cleansing Foam, Cleansing Lotion, Cleansing Cream, Body Lotion and Body Cleanser Wrinkle improvement or anti-aging cosmetic composition, characterized in that any one selected from the group consisting of.
7. Health functional food composition for skin wrinkle improvement and anti-aging containing ginger, creation, turmeric and broiler mixed extract as an active ingredient.
8. According to claim 7, wherein the mixing ratio of the ginger, the production, turmeric and broiler extract is 1: 2.5 ~ 6.5: 2.5 ~ 6.5: 1 weight ratio, the skin functional improvement food for skin wrinkle improvement and anti-aging, characterized in that the noise is cited in filamentous constitution Composition.
9. Pharmaceutical composition for the prevention and treatment of skin wrinkles containing ginger, creation, turmeric and broiler mixed extract as an active ingredient.
10. The pharmaceutical composition according to claim 9, wherein the mixing ratio of the ginger, the extract, the turmeric and the broiler extract is 1: 2.5 to 6.5: 2.5 to 6.5: 1 by weight and is used for noise in filamentous constitution.

Images