KR102655491B1 - Compositions for Improving Skin Wrinkles Using an Extract of Spiraea chinensis - Google Patents

Abstract

The present invention discloses a composition for improving skin wrinkles using a poplar tree extract showing elastase inhibitory activity.

Description

Compositions for Improving Skin Wrinkles Using an Extract of Spiraea chinensis}

The present invention relates to a composition for improving skin wrinkles using Spiraea chinensis extract.

The skin makes up about 16% of the human body, and is in direct contact with the external environment, playing an important role in protecting the human body from external harmful factors such as temperature, humidity, and ultraviolet rays. The skin is composed of the epidermis, dermis, and subcutaneous tissue under the keratin. The epidermis is a thin protective layer composed mainly of keratinocytes, which are made of keratin, melanocytes that produce and secrete melanin, immune cells such as Langerhans cells, and sensory-related cells (Merkel's copuscles). It prevents the invasion of external stimuli and pathogens, regulates body temperature, and maintains moisture and lipid components. The dermis is a connective tissue beneath the epidermis and is mostly composed of a network structure of macromolecules called extracellular matrix. This extracellular stroma is made from fibroblasts and consists of fibrous proteins such as collagen and elastin and polysaccharides such as hyaluronic acid.

As we age, skin cells are damaged due to various pollutants, strong ultraviolet rays, stress, and nutritional deficiencies, and cell proliferation is impaired, causing wrinkles, loss of elasticity, pigmentation, and keratinization in the skin. Gilchrest B.A., J. Am. Acad. Dermatol, 21, 610. 1989).

Collagen is the most important protein in maintaining skin moisture and skin flexibility and elasticity, making up 90% of the dermal layer (J Am Acad Dermatol, 17(4):610-613. 2001), and giving the skin strength and tension. This serves to protect the skin from external stimulation. In addition, elastin in the dermal layer accounts for about 2%, which is less than collagen, but plays a role in supporting collagen fibers. Many recent studies have reported that the deficiency, aggregation, and loss of elastin fibers play an important role in the skin wrinkle formation mechanism. (Weihermann AC et al., Int J Cosmet Sci. 2017 Jun;39(3):241-247; Mora Huertas AC et al., Biochimie. 2016 Sep-Oct;128-129:163-73).

Collagen and elastin are synthesized in fibroblasts and decomposed by collagenase or elastase. As we age or are exposed to ultraviolet rays, the function of fibroblasts and the number of cells decreases, resulting in a decrease in the amount of collagen or elastin synthesis and an increase in the action of collagenase or elastase, which decomposes them. Once the elasticity of the skin caused by collagen and elastin is reduced, it is very difficult to recover. Accordingly, research is being actively conducted to improve skin wrinkles by suppressing elastase activity, which increases with age.

Currently, substances that inhibit skin wrinkle formation include retinoic acid and retinol (Simon C et al., J Invest Dermatol 98: 248-260. 1992; Elaine S et al., J Invest Dermatol 96: 975-978. 1991). Its effectiveness has been proven, and it contains dehydroepiandrosterone (Shin MH et al., J Invest Dermatol 124: 315-323.2005), ginsenoside Rg3 extracted from ginseng (Kim SW et al., J Soc Cosmet Scientists Korea 30: 221-225.2004), and flavonoids ( The wrinkle improvement and skin protection effects of various substances such as Francesco B et al., Int J Pharm 145: 87-94.1996), Sorbus pear extract (Korean Patent No. 101008833), and lotus root extract (Korean Patent No. 100825450) were explored. It has been done. However, there are restrictions on the use of some substances because they have low stability or cause skin irritation, which poses safety issues. Accordingly, the search for substances with excellent anti-wrinkle activity and safety and stability continues.

The present invention discloses the skin wrinkle-improving activity of a poplar tree extract.

The purpose of the present invention is to provide a composition for improving skin wrinkles using a poplar tree extract.

Other or specific purposes of the present invention will be presented below.

The present invention was completed by confirming that the extract of the poplar tree showed elastase inhibitory activity, as confirmed in the examples and experimental examples below.

Considering the above, in one aspect, the present invention can be viewed as a composition for improving skin wrinkles containing a poplar tree extract as an active ingredient.

In this specification, the term "Sugar poplar extract" refers to the extract object, which is the leaves, stems, branches, above-ground parts, underground parts, seeds, flowers, or mixtures thereof, mixed with water and a lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, butanol, etc.). ), methylene chloride, ethylene, acetone, hexane, ether, chloroform, ethyl acetate, butylacetate, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,3-butylene glycol, propylene glycol, or It refers to extracts obtained by leaching using mixed solvents, extracts obtained using supercritical extraction solvents such as carbon dioxide and pentane, or fractions obtained by fractionating the extracts. The extraction method is determined by determining the polarity of the active substance, degree of extraction, and degree of preservation. Considering this, arbitrary methods such as cold immersion, reflux, heating, ultrasonic radiation, and supercritical extraction can be applied. In the case of a fractionated extract, the extract is suspended in a specific solvent and then mixed with a solvent of different polarity to form a fraction obtained by adsorbing the crude extract onto a column filled with silica gel and then mixed with a hydrophobic solvent, a hydrophilic solvent, or a mixture of these. It is meant to include fractions obtained using the mobile phase. In addition, the meaning of the extract includes concentrated liquid extract or solid extract from which the extraction solvent has been removed by methods such as freeze-drying, vacuum drying, hot air drying, and spray drying. Preferably, it refers to an extract obtained using water, a lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, butanol, etc.), or a mixed solvent thereof (especially 50 to 100% (v/v) ethanol) as the extraction solvent.

In addition, in this specification, “active ingredient” refers to an ingredient that exhibits the desired activity alone or can exhibit activity in combination with a carrier that is not active on its own.

In addition to the active ingredients, the composition of the present invention contains similar activities such as skin whitening activity, skin hypersensitivity inhibition activity, and skin protection activity (inhibition of skin damage caused by ultraviolet rays, skin moisturization, etc.) for the purpose of increasing and reinforcing the effect of improving skin wrinkles. In order to improve the convenience of taking, ingesting, or using by adding, any compound or natural extract that has already been proven safe in the art and is known to have the corresponding activity may be additionally included.

These compounds or extracts include the Pharmacopoeia of each country (in Korea, “Korea Pharmacopoeia”), each country’s Code of Health Functional Foods (in Korea, it is “Standards and Specifications for Health Functional Foods” notified by the Ministry of Food and Drug Safety), and the Code of Functional Cosmetics of each country (in Korea, it is the “Standards and Specifications for Health Functional Foods” notified by the Ministry of Food and Drug Safety). Compounds or extracts listed in compendial documents such as “Functional Cosmetics Standards and Test Methods”), compounds or extracts approved as items in accordance with the laws of each country governing the manufacture and sale of pharmaceuticals (in Korea, this is the Pharmaceutical Affairs Act), health Compounds or extracts recognized as functional in accordance with the laws of each country that govern the manufacture and sale of functional foods (in Korea, this is the “Health Functional Foods Act”), and the laws of each country that govern the manufacture and sale of functional cosmetics (in Korea, it is the “Cosmetics Act”) 」) includes compounds or extracts whose functionality has been recognized.

These ingredients include, for example, arbutin, niacinamide, ascorbyl glucoside, alpha-bisabolol, and oil-soluble licorice, which are recognized as skin whitening ingredients in the Cosmetics Code of Korea (Korea Ministry of Food and Drug Safety Notification, “Standards and Specifications for Functional Cosmetics”) in accordance with the Korean Cosmetics Act. Oil Soluble Licorice (Glycyrrhiza) Extract, etc., as well as retinol, retinyl palmitate, adenosine, and polyethoxylated amide, which are recognized as skin wrinkle improvement ingredients in the same Korean Cosmetic International, and UV protection in the same Korean Cosmetic International. Recognized ingredients include drometrizole, drometrizole trisiloxane, digalloyl trioleate, dimethycodiethylbenzalmalonate, diethylhexylbutamidotriazone, pine bark extract, phosphatidylserine, and finger root. Examples include extract powders, complex extracts of red ginseng and Cornus officinalis, etc. In addition, in accordance with Korea's Health Functional Foods Act, functional ingredients for 'improving sensitive skin conditions' include L. sakei Probio 65, oil containing gamma-linolenic acid, and lactic acid bacteria derived from fruit and vegetables. Examples include L.plantarum CJLP133 and probiotic ATP. One or more of these compounds or natural extracts may be included in the composition of the present invention together with the active ingredient.

The composition of the present invention may contain the active ingredient in any amount (effective amount) as long as it can exhibit the wrinkle-improving activity intended for treatment depending on the use, formulation, purpose of formulation, etc., and the typical effective amount is based on the total weight of the composition. It will be determined within the range of 0.001% by weight to 15% by weight. Here, “effective amount” means that when the composition of the present invention is administered to mammals, preferably humans, to which it is applied during the administration period recommended by medical or skin experts, it will produce the intended dermatological and medical effects, such as wrinkle improvement effects. It refers to the amount of active ingredient contained in the composition of the present invention. Such effective amounts can be determined experimentally within the scope of the ordinary ability of those skilled in the art.

In a specific aspect, the composition of the present invention can be viewed as a food composition.

The food composition of the present invention can be manufactured in any form, for example, beverages such as tea, juice, carbonated beverages, and electrolyte drinks, processed oils such as milk and yogurt, gums, rice cakes, Korean snacks, bread, snacks, noodles, etc. It can be manufactured into health functional food preparations such as foods, tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, bars, etc.

In addition, the food composition of the present invention can have any product classification in terms of legal and functional classification as long as it complies with the enforcement laws and regulations at the time of manufacture and distribution. For example, it is a health functional food in accordance with the laws of an excluded country regulating the manufacture and sale of health functional foods (in Korea, this is the “Act on Health Functional Foods”), or it is a health functional food in accordance with the laws of an excluded country regulating the manufacture and sale of food (in Korea, it is the “Act on Health Functional Foods”). According to the Food Sanitation Act (the Food Sanitation Act) (in Korea, it is the Korean Ministry of Food and Drug Safety Notification “Food Standards and Specifications”), it can be confectionery, beans, soy milk, fermented beverages, special purpose foods, etc. according to each food type.

The food composition of the present invention may contain food additives in addition to the active ingredients. Food additives can generally be understood as substances that are added to, mixed with, or infiltrated into food when manufacturing, processing, or preserving food. Since they are consumed daily and for a long period of time with food, their safety must be guaranteed. In the Food Additives Code of Laws of each country that regulates the manufacturing and distribution of food (in Korea, it is the Food Sanitation Act), food additives with guaranteed safety are limited in terms of ingredients or functions. In the Korea Food Additive Code (Ministry of Food and Drug Safety Notification “Food Additive Standards and Specifications”), food additives are classified into chemical synthetics, natural additives, and mixed preparations in terms of composition. These food additives are classified into sweeteners and flavors in terms of function. It is classified into preservatives, emulsifiers, acidulants, thickeners, etc.

Sweeteners are used to impart an appropriate sweetness to foods, and both natural and synthetic ones can be used in the composition of the present invention. Preferably, a natural sweetener is used, and natural sweeteners include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose, and maltose.

Flavoring agents can be used to improve taste or aroma, and both natural and synthetic ones can be used. Preferably, natural products are used. When using natural products, they can serve the purpose of enhancing nutrition in addition to flavor. Natural flavoring agents may be obtained from apples, lemons, tangerines, grapes, strawberries, peaches, etc., or may be obtained from green tea leaves, coriander leaves, bamboo leaves, cinnamon, chrysanthemum leaves, jasmine, etc. You can also use things obtained from ginseng (red ginseng), bamboo shoots, aloe vera, and ginkgo nuts. Natural flavoring agents may be liquid concentrates or solid extracts. In some cases, synthetic flavoring agents may be used, and the synthetic flavoring agents may include esters, alcohols, aldehydes, terpenes, etc.

Preservatives include calcium sodium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, EDTA (ethylenediaminetetraacetic acid), etc., and emulsifiers include acacia gum, carboxymethyl cellulose, xanthan gum, Examples include pectin, and acidulants include acidic acid, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, and phosphoric acid. In addition to improving taste, acidulants may be added to ensure that the food composition has an appropriate acidity for the purpose of suppressing the growth of microorganisms.

As a thickening agent, a suspending agent, settling agent, gel forming agent, bulking agent, etc. may be used.

In addition to the food additives described above, the food composition of the present invention may contain bioactive substances or minerals known in the art and whose safety is guaranteed as food additives for the purpose of supplementing and reinforcing functionality and nutrition.

Such physiologically active substances include catechins contained in green tea, vitamins such as vitamin B1, vitamin C, vitamin E, and vitamin B12, tocopherol, dibenzoylthiamine, etc., and minerals include calcium preparations such as calcium citrate and magnesium stearate. Magnesium preparations such as iron citrate, iron preparations such as chromium chloride, potassium iodine, selenium, germanium, vanadium, zinc, etc. are included.

The food composition of the present invention may contain the above-described food additives in an appropriate amount to achieve the purpose of addition depending on the product type.

Regarding other food additives that can be included in the food composition of the present invention, each country's food code or food additive code can be referred to.

The composition of the present invention may be considered a pharmaceutical composition in other specific embodiments.

The pharmaceutical composition of the present invention contains a pharmaceutically acceptable carrier in addition to the active ingredient and can be prepared into an oral formulation or a parenteral formulation depending on the route of administration by a conventional method known in the art. Here, the route of administration may be any suitable route, including topical route, oral route, intravenous route, intramuscular route, and direct absorption through mucosal tissue, and two or more routes may be used in combination. An example of a combination of two or more routes is a case where two or more dosage forms of drugs according to the administration route are combined, for example, when one drug is administered firstly through an intravenous route and the other drug is administered secondarily through a local route.

Pharmaceutically acceptable carriers are well known in the art depending on the route of administration or dosage form, and for specifics, reference can be made to each country's pharmacopoeia, including the "Korean Pharmacopoeia".

When the pharmaceutical composition of the present invention is prepared as an oral dosage form, it can be prepared as powder, granules, tablets, pills, dragees, capsules, solutions, gels, syrups, suspensions, and wafers using a suitable carrier according to methods known in the art. It can be manufactured in a dosage form such as: Examples of suitable carriers include sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol, and xylitol, starches such as corn starch, potato starch, and wheat starch, cellulose, methylcellulose, ethylcellulose, sodium carboxymethylcellulose, Cellulose such as hydroxypropylmethylcellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, polyol, vegetable oil, ethanol, grease. Serol, etc. can be mentioned. When formulating, appropriate binders, lubricants, disintegrants, colorants, diluents, etc. can be included as needed. Suitable binders include starch, magnesium aluminum silicate, starch ferrite, gelatin, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, glucose, corn sweetener, sodium alginate, polyethylene glycol, and wax, and as a lubricant, oleic acid. Examples include sodium, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, silica, talcum, stearic acid, its magnesium and calcium salts, and polydethylene glycol. Disintegrants include starch and methyl cellulose. , agar, bentonite, xanthan gum, starch, alginic acid or its sodium salt, etc. Additionally, diluents include lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycine, etc.

When the pharmaceutical composition of the present invention is prepared as a parenteral formulation, it can be formulated in the form of injections, transdermal administration, nasal inhalation, and suppositories along with a suitable carrier according to methods known in the art. When formulated as an injection, an aqueous isotonic solution or suspension can be used as a suitable carrier. Specifically, an isotonic solution such as PBS (phosphate buffered saline) containing triethanolamine, sterile water for injection, or 5% dextrose can be used. . When formulated for transdermal administration, it can be formulated in the form of ointments, creams, lotions, gels, external solutions, paste preparations, linear preparations, and aerol preparations. In the case of nasal inhalation, it can be formulated in the form of an aerosol spray using suitable propellants such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, and carbon dioxide. When formulated as a suppository, the carrier is Wethepsol ( witepsol), Tween 61, polyethylene glycols, cocoa fat, laurel paper, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, sorbitan fatty acid esters, etc. can be used.

Regarding the specific formulation of pharmaceutical compositions, it is known in the art, and references can be made to, for example, Remington's Pharmaceutical Sciences (19th ed., 1995). The above documents are considered a part of this specification.

The preferred dosage of the pharmaceutical composition of the present invention is in the range of 0.001 mg/kg to 10 g/kg per day, preferably 0.001 mg/kg to 1 g, depending on the patient's condition, weight, gender, age, patient's severity, and administration route. It may be in the /kg range. Administration can be done once a day or divided into several times. These dosages should not be construed as limiting the scope of the invention in any respect.

In another specific aspect, the composition of the present invention can be considered a cosmetic composition.

Even if the composition of the present invention is identified as a cosmetic composition, the cosmetic composition may be classified as an arbitrary product in terms of its use and by law, and is specifically a functional product with uses such as improving skin troubles, improving skin whitening, and improving atopic dermatitis. It may be cosmetics, non-functional general cosmetics, etc. The product form can take any product form, specifically solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax. It can take the form of products such as foundation or spray. Specific product forms may include softening lotion, nourishing lotion, nourishing cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray, or powder.

In addition to the active ingredient, the cosmetic composition of the present invention may contain ingredients commonly used in cosmetic compositions, such as stabilizers, solubilizers, surfactants, vitamins, conventional auxiliaries such as pigments and flavorings, and carriers.

When the formulation of the present invention is a paste, cream or gel, 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 ingredient. You can.

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder can be used as the carrier ingredient. In particular, when the formulation is a spray, chlorofluorohydrocarbon and propane may be used as carrier ingredients. /May contain propellants such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizing agent, or emulsifying agent is used as a carrier component, specifically water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, fatty acid ester of sorbitan, etc. can be used.

When the formulation of the present invention is a suspension, the carrier ingredients include water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, polyoxyethylene sorbitan ester, and microcrystals. Cellulose, aluminum metahydroxide, bentonite, agar, etc. can be used.

When the formulation of the present invention is a surfactant-containing cleansing agent, the carrier ingredients include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, and fatty acid amide. Ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester can be used.

The cosmetic composition of the present invention can be prepared according to a cosmetic composition manufacturing method commonly used in the art, except that it contains an active ingredient that exhibits skin wrinkle-improving activity.

As described above, according to the present invention, it is possible to provide a composition for improving skin wrinkles using a poplar tree extract.

This composition of the present invention can be commercialized into foods (especially functional foods), cosmetics, drugs, etc.

Figure 1 shows the results of an elastase inhibitory activity experiment.

Hereinafter, the present invention will be described with reference to examples and experimental examples. However, the scope of the present invention is not limited to these examples and experimental examples.

<Example> Preparation of poplar tree extract

Spiraea chinensis Maxim., Extraction part: leaves) 10 times the weight of 70% ethanol was added to the dried powder, leached at room temperature for 24 hours, filtered with Whatman filter paper No. 2, and the filtrate was concentrated under reduced pressure and freeze-dried. A solid extract was prepared.

<Experimental Example> Wrinkle improvement activity test - Elastase Inhibition Assay

After adding samples diluted by concentration to 0.1M Tris-Cl buffer (pH 8.5), 2.9mM N-succinyl-(Ala) ₃ -p-nitroanilide as a substrate was added to 0.1M Tris-Cl buffer (pH 8.5). 0.2U/ml PPE (porcine pancreas elastase) was added, mixed well, reacted at 37°C, and absorbance was measured using an ELISA reader at 410nm. The elastase inhibition ability was measured compared to the control group, which was an untreated sample, and is shown in Figure 1. The results are based on three repeated experiments for each concentration.

Referring to Figure 1, the extract of the example showed elastase inhibitory activity in a concentration-dependent manner.

Claims (4)

A food composition for improving skin wrinkles containing a poplar tree leaf extract as an active ingredient.
According to paragraph 1,
A composition wherein the extract is an extract of water, ethanol, or a mixed solvent thereof.
A cosmetic composition for improving skin wrinkles containing a poplar tree leaf extract as an active ingredient.
According to paragraph 3,
A composition wherein the extract is an extract of water, ethanol, or a mixed solvent thereof.