KR20170025351A - Composition for improving skin - Google Patents
Composition for improving skin Download PDFInfo
- Publication number
- KR20170025351A KR20170025351A KR1020150121692A KR20150121692A KR20170025351A KR 20170025351 A KR20170025351 A KR 20170025351A KR 1020150121692 A KR1020150121692 A KR 1020150121692A KR 20150121692 A KR20150121692 A KR 20150121692A KR 20170025351 A KR20170025351 A KR 20170025351A
- Authority
- KR
- South Korea
- Prior art keywords
- skin
- composition
- extract
- active ingredient
- effects
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- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
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- A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
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Abstract
Description
The present invention relates to a skin improving composition exhibiting skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, antioxidant, anti-inflammatory, atopic improvement, skin moisturizing, skin texture improvement and stem cell activity promoting effect.
Collagen is a major substrate protein produced in fibroblasts of the skin and exists in extracellular epilepsy. Its important functions are mechanical rigidity of skin, resistance of connective tissues and binding force of tissues, support of cell adhesion, division of cells and differentiation Growth or wound healing) are known. Such collagen is reduced by aging and photo aging caused by ultraviolet irradiation, which is known to be closely related to the wrinkling of the skin. Also, in recent years, extensive research on skin aging has developed, and important functions of collagen in skin have been revealed.
Effective ingredients promoting collagen synthesis and exhibiting wrinkle-reducing effects are known. For example, retinoic acid, transforming growth factor (TGF) [non-patent document 1], animal placenta-derived protein [Patent document 1], betulinic acid [Patent document 2], chlorella extract [ Patent Documents 3 and 4] are known as collagen synthesis promoting substances. However, the above-mentioned effective ingredients are limited in the use amount due to safety problems such as irritation and redness when applied to the skin, or have insufficient effect, so that the effect of improving the skin function by promoting the collagen synthesis of the skin can not be expected.
On the other hand, active oxygen introduced from the outside of the living body or generated in the living body causes many problems such as promoting aging of the living body, cancer, and the like. Therefore, the development and research of antioxidants that inhibit oxidation by active oxygen have been performed. Antioxidants are widely distributed in copper and plants. Many phenolic compounds, flavonoids, tocopherols, vitamin C and selenium are known in fruits and vegetables. However, the antioxidant substances present in nature can not be expected to have practically sufficient effects in skin application. Therefore, although synthetic antioxidants having excellent antioxidant ability and low cost are widely used, their use is restricted due to safety concerns such as human side effects.
In addition, inflammation is an immune response of a human body in response to a wound or disease, and oxidative stress such as ultraviolet rays, active oxygen, free radicals, etc. activate inflammatory factors and cause aging of various diseases and skin. The vasoactive polypeptide, kinin, plasmin and complement, have vasodilatory and contraction and chemotaxis effects, as well as lymphokines such as interleukin-6 (IL-6) Phosphorus and arachidonic acid are responsible for inflammation. Arachidonic acid is metabolized through inflammatory mediators such as prostaglandin and lukotrienes via two pathways: cyclooxygenase or lipooxygenase, mediating a variety of inflammatory responses.
On the other hand, in order to eliminate inflammation, elimination of inflammation source, reduction of vital reaction and symptoms is called anti-inflammatory. To date, substances used for antiinflammatory purposes include flutenamic acid, ibuprofen, benzydamine, indomethacin, and steroids, prednisolone, , Dexamethasone, and the like. It is also known that allantoin, azene, hydrocortisone and the like are effective for antiinflammation. However, these materials are limited in their use due to safety of skin, .
In addition, the epidermis located at the outermost part of the skin protects against various external physical, chemical and mechanical stimuli and protects against excessive divergence of body water through the skin. This protective function is possible by normally forming and maintaining the stratum corneum composed of keratinocytes. The keratinocyte is a cell formed by a stepwise change in morphology and function while a basal cell that continuously proliferates in the stratum basale moves to the stratum corneum, Forming cells are removed from the skin and the new keratinocytes from the epidermis's bottom layer repeat the process of epidermis differentiation or keratinization replacing its function. In this keratinization process, keratinocytes produce intercellular lipids such as natural moisturizing factors (NMF) and ceramides, cholesterol, and fatty acids, which act as barrier layers to the outside, As shown in Fig.
In addition, skin dryness, which is considered to be one of the major diseases of modern society, is one of the symptoms caused by skin barrier function abnormality. Recently, environmental pollution, increase in dry environment such as apartments and high rise building, increase in social stress, Of excessive bathing, skin aging, and the like, and the cases of severe symptoms and the need for treatment are also increasing steadily.
Atopic dermatitis, which is present in 10% of children in recent years, is also known to be a cause of dry skin syndrome, and more fundamentally, abnormal skin barrier function. In order to treat such atopic dermatitis, studies have been carried out in order to supply water from the outside or minimize water loss from the body by focusing on proper moisture retention in the skin in the past. Actually, ceramide or derivatives thereof have been developed and are widely used in the pharmaceutical or cosmetic field.
However, the use of such a moisturizing agent is not only a fundamental treatment but a temporary symptom relief, and thus has not shown sufficient effect for treatment of dry skin and skin barrier function including atopic dermatitis. Therefore, it is urgent to develop a substance that can restore the damaged skin barrier fundamentally.
Recently, it has been known that PPAR alpha (peroxisome proliferator activated receptor-alpha) present in keratinocyte cells is activated by binding to its ligand, thereby promoting the differentiation of keratinocytes and reconstructing damaged skin barrier. In the case of applying Clofibrate (non-patent document 2) or WY 14643 (non-patent document 3), which is an agonist of known PPAR alpha, to the skin of which skin barrier is damaged, differentiation of keratinocytes is promoted And recovery of the skin barrier is promoted.
In addition, it is the desire of everyone to have a whiter skin. It is genetically determined by the concentration and distribution of melanin in human skin, but is also influenced by environmental or physiological conditions such as sunlight, fatigue, and stress. Melanin is produced by a nonenzymatic oxidation reaction after tyrosine, an amino acid, is converted to DOPA or dopaquinone by an enzyme called tyrosinase. Thus, the pathway through which melanin is made is known, but the mechanism by which melanin synthesis, the previous step in which tyrosinase acts, is not yet elucidated.
On the other hand, commonly known whitening ingredients include substances inhibiting the activity of tyrosinase enzymes such as kojic acid and arbutin, hydroquinone, vitamin C (L-Ascorbic acid) There are plant extracts. By inhibiting the synthesis of melanin pigment, they can brighten the skin tone to realize skin whitening, and it is possible to improve skin hypercholesterolemia such as stain or freckles due to ultraviolet rays, hormones or heredity. However, when applied to skin, there is a problem that the use amount is limited due to safety problems such as irritation and redness, or the effect is insignificant so that a substantial effect can not be expected.
In addition, the skin texture, which is the shape of the skin surface, is characterized by a three-dimensional microstructure formed by fine lines and is significantly different according to age and site. The skin texture is divided into primary (about 20-100 μm), secondary (about 5-40 μm), and tertiary (about 0.5 μm) lines depending on the depth of the line. And has a distinctive polygonal shape and star formation due to the contact of the lines [Non-Patent Document 4].
However, as the age increases or the skin becomes damaged, the network structure of the dense fine lines collapses and fine lines (secondary, tertiary, etc.) disappear and the primary lines become deeper and wrinkles are known to be produced 5,6]. In other words, wrinkles, a typical sign of skin aging, are accumulations of minute changes that have already occurred over a long period of time.
Embryologically, all components of human skin are known to originate from ectoderm or mesodermal lobe. Epidermis, hair follicles, sebaceous glands and glands are originated from ectoderm, and melanocytes, nerves and special sensory receptors are derived from neuroepithelial cells. According to the developmental stage, the embryonic stem cells are repeatedly differentiated and become cells with the characteristics of each tissue function. After the embryo, a certain number of stem cells remain in the tissue. . The first is in the hair follicle. It is known to play an important role in the regeneration of the epidermis into cells before cell differentiation occurs, and plays an important role in hair regeneration and growth. The second is the basal layer of the epidermis. The stem cells found here play an important role in maintaining skin health by administering not only the epidermis but also the fibroblasts of the dermal layer. The stem cells here are relatively large in quantity and easy to obtain, making them widely used in the study of skin stem cells. The skin is constantly renewed, and stem cells present in the epithelium of the skin, that is, epidermal stem cells of the skin, are involved in the repair of the epithelium after injury [Non-Patent Document 7]. The epithelial stem cells of the skin are also referred to as skin stem cells. When the skin stem cells are activated, it is possible to treat skin wounds such as trauma, promote wound healing, have. Integrin β1 and integrin α6 are used as indicators of dermal stem cells, and maintenance of skin stem cells necessary for epithelial morphogenesis and differentiation has been reported to be regulated by p63 protein.
Dermal stem cells play an important role in maintaining the health and physiological and biochemical homeostasis of the skin. Stem cells present in the skin are also abnormally functioned due to the effect of aging, and thus various problems arise as the homeostasis of the skin is broken. Therefore, it is possible to improve various phenomena of skin aging through the activation of stem cells [Non-Patent Document 8].
In addition, it is more effective than a substance that is safe in the living body, stable in its active ingredient, and most of all has the effect of regenerating skin, improving wrinkles, improving elasticity, skin whitening, antioxidation, antiinflammation, Development of ingredients having skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, antioxidant, anti-inflammation, atopic improvement, skin moisturizing and skin tone improving activity is urgently required.
On the other hand, Mohwangryun (황 황 련 또는 또는 풀 풀) et Hook. Or Plagiorhegma dubium Maxim, a Berberidaceae plant, whose roots are used as medicinal plants and distributed in the central, northern part of Korea, and northeastern part of China. The main components include alkaloids and saponins. Representative alkaloids include berberin, palmatine, and the like. Mohwangryun has been used in oriental medicine for a long time. Human safety has already been confirmed by ingestion. It is an extremely safe plant with little irritation to the skin and mucous membranes. In addition, in patients with bronchial asthma, bronchial asthma is effective for inflammation, sedation, nervous anxiety, hyperemia and inflammation. It is also known to be effective for dyspepsia and gastritis as well as for strong infestation. "Ingredients and Usage of Herbs", Jan.
Accordingly, the present inventors have found that the extracts of the present invention promotes the proliferation of skin stem cells, promotes skin regeneration, promotes collagen synthesis of fibroblasts of the skin to improve wrinkles, improve elasticity, inhibit melanin synthesis, It exhibits antioxidative effect by eliminating free radicals, has an anti-inflammatory effect by inhibiting NO production, has excellent activity of PPAR alpha, has an effect of improving atopy, exhibits skin moisturizing effect due to increased expression of filar green, The present invention has been accomplished by confirming the effect of stimulating stem cell activity because it promotes the proliferation of skin stem cells and exhibits a stem cell maintenance effect.
Accordingly, it is an object of the present invention to provide a composition for improving skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, antioxidation, anti-inflammation, atopic improvement, skin moisturization and skin texture improvement,
Another object of the present invention is to provide a composition for promoting stem cell activity comprising the following extract as an active ingredient.
As a means for solving the above-mentioned problems, the present invention provides a method for producing a medicament, a cosmetic preparation or a food, comprising the steps of: skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, antioxidant, antiinflammation, A composition for skin moisturization and skin texture improvement.
As another means for solving the above-mentioned problems, the present invention provides a composition for stimulating stem cell activity, comprising an extract of Lycoris chejuensis as an active ingredient, for the production of cosmetic formulations.
The extract according to the present invention promotes the proliferation of skin stem cells to promote regeneration of skin, promotes collagen synthesis of fibroblasts of the skin to improve wrinkles, improve elasticity, inhibit melanin synthesis, exhibit a whitening effect , Anti-inflammatory effect by suppression of free radicals by exhibiting antioxidative effect by abolishing free radicals, anti-inflammatory effect by PPAR alpha activity, improvement of atopy, improvement of skin moisturization by increase of fila green expression, improvement of skin brightness And thus can be used for the manufacture of medicines, cosmetics or foods.
In addition, the extract of Lycoris chejuensis promotes proliferation of dermal stem cells and exhibits a stem cell-retaining effect, so that it can be used in the production of cosmetic formulations for promoting stem cell activity.
Hereinafter, the configuration of the present invention will be described in detail.
To regenerate skin, improve wrinkles, improve skin elasticity, whitening skin, antioxidant, anti-inflammation, atopic skin, skin moisturizing and improving skin texture, It exhibits the activity of improving elasticity, skin whitening, antioxidation, anti-inflammation, atopic improvement, skin moisturizing and skin tone improving activity and is excellent in ability to permeate and absorbed through the skin and is excellent in skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, Is low in volatility so as to be able to stay for a sufficient time to exhibit inflammation, atopic improvement, skin moisturizing and skin texture improving effect, and stably maintains the active ingredient on the composition or skin and is easy to manufacture into medicines, It is also preferred that it is skin-safe. However, the components satisfying all of the above-mentioned characteristics among the known components are not common. For example, some skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, antioxidant, antiinflammatory, atopic improvement, skin moisturizing and skin tone improving ingredients can be used for skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening , Antioxidant, antiinflammation, atopic improvement, skin moisturizing and skin texture improving activity, but it is difficult to apply to the actual skin because of its ability to be absorbed through the skin. Other active ingredients have low hydrophilicity, making them difficult to formulate into medicines, cosmetics, and foods. In addition, some of the skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, antioxidant, anti-inflammatory, atopic improvement, skin moisturizing and skin tone improving ingredients may cause the active ingredient to decompose when exposed to heat, light, In some cases, the effect disappears before it is deformed and applied to the skin.
As can be seen in the following examples, the extract of Mohwangryun extract has remarkably excellent proliferation promoting effect on collagen synthesis, melanin formation inhibitory effect, antioxidative effect, anti-inflammatory effect, PPAR alpha activity effect, Cosmetic composition or food composition for skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, antioxidation, anti-inflammation, atopic improvement, skin moisturization and skin texture improvement have.
Accordingly, the present invention provides a composition for improving skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, antioxidation, antiinflammation, atopic improvement, skin moisturization and skin texture improvement,
In the present invention, the term " mother < RTI ID = 0.0 > et Hook. Or Plagiorhegma dubium Maxim, a Berberidaceae plant, also known as pre-fermented or ginger
The extract can be extracted by a method known in the art, and the method is not particularly limited. Alternatively, commercially available extracts can be used.
Preferably, the extract of the present invention may be an extract obtained by extracting a parent strain with water and / or an organic solvent. The organic solvent may be a polar organic solvent, a nonpolar organic solvent or a mixture thereof. The polar organic solvent may be a lower alcohol having 1 to 5 carbon atoms, ethyl acetate or acetone, and the nonpolar organic solvent may be ether, chloroform, benzene, hexane or dichloromethane. For example, the lower alcohol having 1 to 5 carbon atoms may be methanol, ethanol, propanol, butanol or isopropanol.
In one embodiment, the extract may contain a fraction obtained by fractionating the primary extract extracted using the above-described extraction solvent with an extraction solvent having a different polarity. For example, the extract may be a fraction obtained by extracting with an alcohol having 1 to 5 carbon atoms and then fractionating again with a solvent having a different polarity such as ether, benzene or hexane. Two or more kinds of solvents may be used for the fractionation, and the solvent extracts may be sequentially used or mixed according to the polarity of the solvent.
In the present invention, the extracted extract or the fraction obtained by performing the fractionation process may be filtered, concentrated or dried to remove the solvent, and the filtration, concentration, and drying may all be performed. Specifically, the filtration can be performed using a filter paper or a vacuum filter, and the concentration can be reduced by using a reduced pressure concentrator or the like, and the freeze-drying method can be carried out for drying.
The fractions obtained by performing the above-described extract or the fractionation process can be further purified by silica gel column chromatography, thin layer chromatography or high performance liquid chromatography Further purification can be achieved by purification using various chromatographic techniques.
The compositions of the present invention may be used for the manufacture of pharmaceutical formulations.
The pharmaceutical formulations may be in the form of solutions, suspensions or emulsions in oils or aqueous media, or in the form of excipients, powders, granules, tablets or capsules.
In addition, the composition may further contain one or more active ingredients showing the same or similar functions. For example, it may contain known skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, antioxidation, antiinflammation, atopic improvement, skin moisturizing and skin texture improving ingredients. When the composition of the present invention contains the ingredient for improving skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, antioxidant, anti-inflammation, atopic improvement, skin moisturizing and skin texture improvement, skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, , Anti-inflammation, atopic improvement, skin moisturizing and skin texture improving effect can be further enhanced. When the above ingredients are added, skin safety, easiness of formulation, and stability of effective ingredients can be considered according to the combined use. In one embodiment of the present invention, the composition is a skin regeneration component known in the art comprising retinoic acid, TGF, protein from animal placenta, betulinic acid and chlorella extract, antioxidant components known in the art, such as tocopherol, selenium , Vitamin C and phenolic compounds, whitening ingredients known in the art, substances inhibiting the activity of tyrosinase enzymes such as kojic acid and arbutin, hydroquinone, vitamin C (L- Ascorbic acid, derivatives thereof, and various plant extracts. The additional ingredient may be contained in an amount of 0.0001 to 10% by weight based on the total weight of the composition, and the content range may be adjusted according to requirements such as skin safety and ease of formulation of the extract.
In addition, the composition of the present invention may further comprise a pharmaceutically acceptable carrier.
Pharmaceutically acceptable carriers may contain a variety of ingredients such as buffer, injectable sterile water, normal saline or phosphate buffered saline, sucrose, histidine, salts and polysorbates, and the like.
The composition of the present invention can be administered orally or parenterally, and can be administered in the form of a general pharmaceutical preparation, for example, various forms of oral and parenteral administration at the time of clinical administration. In the case of formulation, a filler, , A binder, a wetting agent, a disintegrant, a surfactant, and the like.
Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like. These solid preparations can be prepared by mixing the pharmaceutical composition of the present invention with at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin and the like can be prepared.
In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Examples of liquid formulations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used.
Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
In the present invention, the term 'skin regeneration effect' refers to the recovery of skin tissue against damage caused by external or internal causes of skin as the activity of skin stem cells is promoted. At this time, the damage caused by the external cause may include ultraviolet rays, external pollutants, wound or trauma, and the damage caused by the internal cause may be stress.
In the present invention, the term " wrinkle-reducing effect " refers to inhibiting or inhibiting the generation of wrinkles on the skin, or alleviating already-generated wrinkles.
In the present invention, the 'elasticity-enhancing effect' refers to an increase in elasticity to the skin, which suppresses or inhibits the loss of elasticity of the skin, or alleviates the already-reduced elasticity.
In the present invention, the 'whitening effect' refers to not only brightening the skin tone by inhibiting the synthesis of the melanin pigment but also improving skin hypercholesterolemia due to ultraviolet rays, hormones or heredity, such as spots or freckles.
In the present invention, the term 'antioxidative effect' refers to the action of free radicals or reactive oxygen species (ROS), which are highly reactive according to oxidative stress caused by intracellular metabolism or ultraviolet rays, Refers to inhibition of oxidation, and includes removal of free radical or reactive oxygen species, thereby reducing damage to the cells.
In the present invention, the term 'anti-inflammatory effect' refers to inhibition of inflammation. The inflammation is one of defensive responses of biological tissues to certain stimuli, and involves three types of tissue degeneration, circulatory disorder, exudate, and tissue proliferation Complex lesions. More specifically, inflammation is part of congenital immunity and, like in other animals, human congenital immunity recognizes a pattern of cell surfaces that are specifically present in a pathogen. Phagocytes recognize cells with such surfaces as non-magnetic and attack pathogens. If pathogens break through the physical barriers of the body, an inflammatory reaction occurs. Inflammation is a nonspecific defense that creates hostile environments for microorganisms entering the wound. In the inflammatory response, white blood cells that are responsible for the early stage of immune response, when wounded or infected, enter the body to express cytokines. Therefore, the expression level of intracellular cytokine is an index of inflammatory response activation. Examples of skin diseases associated with inflammation include atopic dermatitis, psoriasis, radiation, chemical substances, inflammatory diseases caused by burns, acid burns, vesicular dermatosis, visceral type diseases, itching due to allergies, seborrheic eczema, rose acne, Inflammatory hair loss such as pemphigus vulgaris, polymorphous exudative erythema, erythema nodosum, erythematosus, pharyngitis, alopecia areata, skin T-cell lymphoma, and the like.
In the present invention, the term 'atopic improvement effect' refers to the effect of preventing and treating skin diseases such as atopy and dry skin, and is to inhibit, inhibit, or alleviate atopic symptoms.
In the present invention, the term 'moisturizing effect' refers to inhibiting or reducing the reduction of moisture in the skin, or increasing the moisture content of the skin to smooth and smooth the surface of the skin.
In the present invention, the term " skin texture improving effect " refers to smoothing the skin surface, imparting gloss, and brightening the skin tone by inhibiting or inhibiting roughness of the skin surface due to aging, stress, .
In the present invention, the term "effective amount" refers to an amount effective for promoting regeneration of damaged skin, improving wrinkles, improving elasticity, exhibiting a whitening effect, inhibiting or alleviating oxidation of cells, Refers to the amount of the extract which can improve the skin dryness such as atopy, or can improve the moisturizing effect and skin texture. When the composition of the present invention contains an effective amount of the extract of the present invention, it is preferable that the skin regeneration effect, the wrinkle improvement effect, the elasticity enhancement effect, the skin whitening effect, the antioxidative effect, the antiinflammatory effect, the atopy improvement effect, Can be provided. The effective amount of the extract of the present invention contained in the composition of the present invention will vary depending on the form in which the composition is commercialized, the manner in which the compound is applied to the skin, and the time on the skin. For example, when the composition is commercialized as a pharmaceutical formulation, it may contain the extract of the present invention at a higher concentration than that of a cosmetic product applied to skin on a daily basis. Accordingly, the daily dose is 0.1 to 100 mg / kg, preferably 30 to 80 mg / kg, more preferably 50 to 60 mg / kg, and 1 to 6 mg / ≪ / RTI >
The composition of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.
The pharmaceutical formulations of the present invention may include external preparation for skin.
When the extract of the present invention is used as an external preparation for skin, it may further contain at least one selected from the group consisting of fatty substances, organic solvents, solubilizers, thickening agents and gelling agents, softening agents, antioxidants, suspending agents, stabilizers, foaming agents, For example, water, ionic or nonionic emulsifiers, fillers, sequestering agents and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or external preparations for skin And any other ingredients used, such as those commonly used in the field of dermatology. The components can also be introduced in amounts commonly used in the field of dermatology.
When the extract is provided as an external preparation for skin, it may have a formulation such as, but not limited to, an ointment, a patch, a gel, a cream or a spray.
Furthermore, the composition for improving skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, antioxidation, anti-inflammation, atopic improvement, skin moisturizing and skin texture improvement of the present invention can be used for the production of cosmetic formulations.
The cosmetic formulation may be in the form of a conventional emulsion formulation and a solubilized formulation. For example, creams, essences, cosmetic creams, sprays, gels, packs, sunscreens, make-up bases, liquids such as lotions such as lotion, facial lotion, body lotion, A powder, a cleansing lotion, a makeup removing agent such as a cleansing oil, a cleansing foam, a soap, a body wash, and the like.
In addition, the cosmetic product may further contain a lipid component, an organic solvent, a solubilizing agent, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, As used herein means any emulsion or emulsion which is commonly used in emulsifying or emulsifying agents, fillers, sequestering and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or cosmetics Adjuvants commonly used in the cosmetics field, such as other ingredients.
The cosmetic formulation may contain a relatively high concentration of the extract of the present invention in the case of a wash-off type cosmetics such as a make-up remover, a detergent, etc. in which the active ingredient remains on the skin in a short period of time. On the other hand, in the case of leave-on type cosmetics such as lotion, cream, essence and the like in which the active ingredient remains on the skin for a long period of time, It may be possible. In one embodiment of the present invention, but not limited thereto, the composition may comprise from 0.0001% to 10% by weight (preferably 0.0001% to 1% by weight) have. When the composition of the present invention contains less than 0.0001% by weight of the extract of the present invention, sufficient skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, antioxidation, antiinflammation, atopic improvement, skin moisturizing, If it is contained in an amount of more than 10% by weight, it is intended to prevent an undesired reaction such as allergy or a problem of skin safety.
Also, the composition for skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, antioxidant, anti-inflammation, atopic improvement, skin moisturizing and skin texture improvement of the present invention can be used for manufacturing food formulations.
The food formulation refers to a food prepared by adding the above extract to a food material such as beverage, tea, spice, gum, confectionery, or the like, or encapsulating, pulverizing, or suspending.
Since the food preparation can be taken on a daily basis, it is very useful because it can expect high skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, antioxidation, antiinflammation, atopic improvement, skin moisturization and skin texture improvement.
When the extract is used as a food additive, the extract may be added as it is or may be used together with other food or food ingredients, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to its intended use (prevention, health or therapeutic treatment). Generally, the composition of the present invention is added in an amount of not more than 15 parts by weight, preferably not more than 10 parts by weight, based on the raw material, when the food or beverage is produced. However, in the case of long-term consumption intended for health and hygiene purposes or for health control purposes, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range .
There is no particular limitation on the kind of the food. Examples of foods to which the above substances can be added include dairy products including meats, sausages, breads, chocolates, candies, snacks, confections, pizza, ramen noodles, gums, ice cream, soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include health foods in a conventional sense.
When the food is a beverage, various flavors or natural carbohydrates may be added as an additional ingredient such as a normal drink. The above-mentioned natural carbohydrates are sugar alcohols such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the composition of the present invention.
In addition to the above, the food formulations may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, And the like. Other food formulations may contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
The present invention also provides a composition for stimulating stem cell activity, comprising the above extracts as an active ingredient.
The term 'stem cell' in the present invention is a cell capable of cell division by itself and capable of differentiating into a very specific type of specific cell type. The type of such stem cells is not particularly limited, and in one embodiment, the stem cells may be dermal stem cells. The term 'dermal stem cells' refers to stem cells that can be differentiated into cells constituting the skin (epidermis, dermis and subcutaneous fat layer). The cells that make up the skin include keratinocytes, melanocytes, and fibroblasts (mainly responsible for biosynthesis of collagen and elastin) present in the epidermis.
The kind of the skin stem cell is not particularly limited. The dermal stem cells used in the present invention can be used irrespective of where they originate from. For example, dermal stem cells may be obtained from a known source of dermal stem cells, e. G., From the basal layer of hair follicles or epidermis, and the animal to be harvested may be a mammal. In one embodiment, the mammal may include, but is not limited to, a human, a mouse, a rat, a guinea pig, a rabbit, a monkey, a pig, a horse, a cattle, a sheep, Preferably the mammal can be human. Such methods of obtaining dermal stem cells from dermal stem cell sources are well known in the art.
In the present invention, the term 'promoting effect on stem cell activity' refers to an effect of promoting stem cell proliferation and / or an effect of maintaining stem cell characteristics, which is a specific indicator molecule and a self-cleaving property of stem cells.
In addition, the compositions of the present invention can be used for the production of cosmetic formulations. These cosmetic formulations are the same as those described in the description of cosmetic formulations including the extract of Mochujiri extract.
Hereinafter, the present invention will be described in detail with reference to examples. However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.
Manufacturing example One: Mohwang Preparation of extract
The extracts were washed and powdered, and then cooled in a 10-fold volume of ethanol for 5 days. The extract solution was filtered and concentrated to obtain an extract. To this was added a mixed solution of purified water and ethanol to dissolve and then filtered to prepare a final extract.
Manufacturing example 2: Serum-free Under medium conditions Of dermal stem cells culture
Human epidermal stem cells purchased from Cellntec were added to 48-well plates (6 × 10 3 cells / well), supplemented with BPE (bovine pituitary extract) similar to fetal bovine serum And cultured for 24 hours at 5% CO 2 and 37 ° C using CNT-57 medium (Cellntec). Then, the removal through the medium-introducing tube, and then, PBS solution used to remove the medium components the (GibcoBRL Co.), and the process the parent goldthread extract 5ug / ml in the CNT-57 medium that does not include BPE 5% CO 2, and And cultured at 37 ° C for 72 hours.
Experimental Example One: CCK -8 Through evaluation method Dermal stem cells Proliferation promoting effect
The skin stem cells cultured in Preparation Example 2 were evaluated for CCK-8 (Cell counting kit-8). The CCK-8 assay is an indirect method of measuring the density of living cells by measuring the absorbance of Formazan, a dehydrogenase in the intracellular electron transport system, produced by the decomposition of tetrazolium salt.
Cells were treated spectrophotometrically by treating CCK-8 solution (treated with 1/10 of the medium volume) at 37 ° C for 2 hours and then measuring the absorbance at 450 nm. From the measured absorbance value, the proliferation rate (%) of the stem cell of the extract was determined according to the following equation (1) in comparison with the control group (CNT-57 medium supplemented with BPE) and the value thereof is shown in Table 1 below.
[Equation 1]
Growth rate (%) = (absorbance of sample-treated group / absorbance of control group) x 100
As shown in Table 1, the skin stem cells under the medium conditions treated with the extract of Lycopersicon esculentum showed an excellent proliferation promoting effect.
Experimental Example 2: Of dermal stem cells Stem cell ( stemness ) Confirm maintenance effect
The expression level of p63 was evaluated in order to confirm the stem cell maintenance effect of the dermal stem cells cultured in Production Example 2 above. p63 is an intracellular transcription factor and is well known as a maintenance marker for dermal stem cells. Cells were isolated and cDNA was synthesized. Then, real-PCR was performed with Taqman staining solution to measure the expression level of p63. The concentration of RNA in this experiment was normalized to S16 ribosomal RNA.
The experimental results are shown in Table 2 below. In Table 2 below, the numerical value of the increase in p63 is a multiple of the control group (CNT-57 medium supplemented with BPE).
As shown in Table 2, the medium conditions treated with the extracts of Pseudomonas aeruginosa promoted the expression of p63 in the skin stem cells, and thus the stem cell maintenance effect was excellent.
Example 1: Promoting collagen synthesis
The extracts of Mohwangryeon were added to the culture medium of human - derived fibroblasts to examine the promoting effect of collagen synthesis at the cellular level. The biocompatible collagen was quantitated using a PICP EIA kit (Procollagen Type I C-Peptide Enzyme Immunoassay Kit).
(7 × 10 4 cells / cm 2 ) with vitamin C and a control (no supplement) to a final concentration of 10 μg / mL and 20 μg / mL, respectively. After culturing for one day, the culture broth was taken and the degree of collagen biosynthesis at each concentration was measured at 450 nm using a spectrophotometer with a PICP EIA Kit. The collagen biosynthesis performance was calculated by the relative performance relative to the control group and the results are summarized in Table 3 below.
As shown in Table 3, the extract of Mohwangryun extract has excellent collagen synthesis ability against human-derived fibroblasts, and it is possible to obtain a better collagen synthesis effect at a lower concentration than that of vitamin C, which is generally known to have collagen synthesis ability .
Example 2: Whitening effect - Confirmation of melanin formation inhibitory effect
(Lotan R., Lotan D. Cancer Res. 40: 3345-3350, 1980) was added to the culture of mouse melanoma cells (B-16 mouse melanoma cell) . At this time, the toxicity of the melanoma cells of the rats before the experiment was evaluated, and the whitening evaluation was performed by selecting the concentration without toxicity.
The control group, arbutin, was added to the medium to a final concentration of 200 μg / mL, and treated with B-16 melanoma cells for 3 days. The final concentration was 10 μg / mL and 20 μg / mL, Lt; / RTI >
Cells were then trypsinized, detached from the culture, centrifuged, and extracted with melanin. The removed cells were incubated with 1 mL of sodium hydroxide solution (1N), boiled for 10 minutes to dissolve melanin, and the absorbance was measured at 400 nm using a spectrophotometer to measure the amount of melanin produced.
The amount of melanin was measured by an absorbance of 10 6 cells per unit cell, and the amount of melanin produced relative to the control group was calculated as inhibition (%). The results are summarized in Table 4 below.
As shown in Table 4, it can be seen that the extracts of Panax notoginseng extract have remarkably superior melanin production inhibitory effect on the melanoma cells of the rat cultured as compared with the known whitening substance albutin.
Example 3: Antioxidant effect - Free radical scavenging rate
Free radical scavenging activity was measured to confirm the antioxidative activity of the extracts. Free radical scavenging activity was measured using DPPH. DPPH was purchased from Sigma Co. (Sigma Co., Ltd, USA) and used.
First, a standard DPPH ethanol solution of 1.5 mM (0.06 mg / mL) was prepared. Then, ethanol was added to the ascorbic acid, an antioxidant, as a reference substance and a reference material, respectively, to prepare samples at concentrations of 50 μg / mL, 25 μg / mL, 12.5 μg / mL, 6.25 μg / mL and 3.125 μg / mL. Then, the sample and standard DPPH solution were added at the same ratio, stirred well, reacted at 37 ° C for 30 minutes, and absorbance was measured at 520 nm. At this time, ethanol was added instead of the sample to give a control group. Free radical scavenging activity and the results are obtained for the IC 50 half maximal inhibitory concentration (median inhibition) shown in Table 5. IC 50 is a common method of expressing the free radical scavenging ability as a concentration of ascorbic acid and the extracts of Phellinus linteus, which are required to remove 50% of the free radicals of the no-added control group.
As shown in Table 5, it can be seen that the extracts of Pseudomonas aeruginosa exhibit antioxidative effects because they exhibit higher activity than ascorbic acid, a known antioxidant.
Example 4: Anti-inflammatory effect -NO generation inhibitory effect
In order to confirm the anti-inflammatory effect and the skin troubles of the extracts of Mohwangryeon, nitric oxide (NO) formation inhibition experiment was performed by GRIESS using RAW264.7 cell line (ATCC number: CRL-2278).
Specifically, RAW264.7 cells, macrophages of mice, were subcultured several times, placed in 24-well plates at 3 × 10 5 per well, and cultured for 24 hours. Subsequently, the cell lysate extract was diluted with the concentrations shown in Table 6 below and replaced with the cell culture medium. At this time, 20 μg / mL of L-NMMA (L-NG-Monomethylarginine), which is an inhibitor of NO production, was treated with a positive control and cultured for 30 minutes. Lipopolysaccharide (LPS) Lt; / RTI > 100 μl of the supernatant was transferred to a 96-well plate, and 100 μl of the GRIESS solution was added thereto at room temperature for 10 minutes. The absorbance at 540 nm was measured to determine the NO inhibitory effect of Compound 1, Table 6 shows the results.
As shown in Table 6, it can be seen that the extract of Lycoris chejuensis has an inhibitory effect on NO production equivalent to that of L-NMMA, a known anti-inflammatory substance.
Example 5: PPAR Verification of Alpha Activation Promotion Effect
In order to confirm the promoting effect of PPAR alpha activation on the extracts, C2C12 cells (ATCC CRL-1772), a mouse myoblast cell line, were subcultured in DMEM (Dulbecco's Modified Eagle's Medium) medium containing 10% fetal bovine serum. As the vector used herein,
1) A DNA fragment encoding GAL4-DBD (DNA Binding Domain), which is a transcription factor of yeast, and Ser 167 to Tyr 468 in human PPAR alpha LBD (Ligand Binding Domain), into a SV40 promoter of pZEO vector (Invitrogen) NM 005036);
2) a GAL4 response sequence inserted into a multiple restriction enzyme recognition site of a pGL3 vector (Promega) expressing luciferase and 3) a vector inserted into a transfection internal control with? -Galactosidase β-galactodisase) was used.
The cultured cells were plated on a 24-well plate at a concentration of 4 × 10 4 and cultured for 12 hours. The three types of plasmid genes were transiently transfected using lipopectamine . After 8 hours, the extracts were treated for 12 hours, washed with 1 x PBS, lysed with 1 × reporter lysis buffer, and luciferase assay kit (Promega) and β The activity of luciferase was measured using a galactosidase assay kit (Promega). That is, the PPAR alpha activity was measured as " luciferase activity / beta -galactose activity ".
Wy-14,643 (Calbiochem), the most potent ligand of PPAR alpha, was used as a positive control in this experiment, and DMSO 0.05% was used as a negative control.
According to the above experimental method, the activity of PPARalpha according to the concentration was examined by treating the extract of Wakanthiae radix with C2C12 cells. The results are shown in Table 7 below. The values of PPAR alpha activity in Table 7 below represent percentages relative to the negative control (0.05% DMSO).
As shown in Table 7, compared with the positive control group, the extracts of P. vivax showed very strong PPAR alpha activity.
Example 6: Filaggrin's Promoting effect of expression
After incubation for 1 day, the cell RNA was isolated and cDNA was synthesized. The cDNA was synthesized by Taqman staining solution and Real (5 μg / mL, 10 μg / mL) was added to the culture media of human keratinocyte HaCaT cells. -time PCR was performed. The RNA concentration was normalized to S16 ribosomal RNA.
As shown in Table 8, the extracts of Phellodendron chrysanthemum extract have the ability to promote pilar green expression of human horny cell line HaCaT cells.
Example 7: On the turn-over improvement Efficacy
About the nutritional cream of the following formulation example 2, the effect of the improvement of the exfoliation of the skin in the healthy twenties to 50 women was tested as follows.
Twenty of 20 women aged 20 to 50 years were given a 1.5% solution of DHA (Dihydroxyacetone, Sigma Aldrich, USA) for 8 hours, followed by deposition. The preparation cream was applied twice daily to the test site. After 4 days of application, 8 days after application, 12 days after application, photographs were taken using instrument Chromameter CR-400 (Minolta, Japan) and skin lightness of DSLR and DSLR. The measured values were evaluated by three mean values excluding the maximum value and the minimum value. The higher the improvement in the skin brightness of the deposition site, the better the improvement of the exfoliation. The results are shown in Table 9 below.
As shown in Table 9, when the nutritional cream according to the present invention was used, it was found that the exfoliation of the skin was improved.
Formulation example 1: Manufacture of pharmaceutical preparations
1. Preparation of tablets
Mohwangryun extract 0.2mg
100 mg of corn starch
100 mg of milk
2 mg of magnesium stearate
After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.
Formulation example 2: Manufacture of cosmetics
1. Manufacture of nutritional cream
As shown in the following composition, a nutritional cream containing an extract of Lycoris chejuensis as an active ingredient was prepared by a conventional method.
0.2%
Beta-1,3-glucan 5.0 wt%
Wax 10.0 wt%
Polysorbate 60 1.5 wt%
≪ tb > < tb > < tb >
0.5% by weight of sorbitan sesquioleate
Liquid paraffin 10.0 wt%
Squalane 5.0 wt%
Caprylic / capric triglyceride 5.0 wt%
Glycerin 5.0 wt%
3.0% by weight of butylene glycol
3.0% by weight of propylene glycol
0.2% by weight triethanolamine
Preservative 0.05 wt%
0.05% by weight of pigment
0.05% by weight fragrance
Purified water to 100%
Formulation example 3: Preparation of external preparation for skin
1. Manufacture of ointment
As shown in the following composition, an ointment containing an extract of Lycoris chejuensis as an active ingredient was prepared according to a conventional method.
0.5 wt%
Beta-1,3-glucan 10.0 wt%
Wax 10.0 wt%
Polysorbate 60 5.0 wt%
≪ tb > < tb > < tb >
0.5% by weight of sorbitan sesquioleate
Vaseline 5.0 wt%
Liquid paraffin 10.0 wt%
Squalane 5.0 wt%
SHARE BUTTER 3.0 wt%
Caprylic / capric triglyceride 5.0 wt%
Glycerin 10.0 wt%
Propylene glycol 10.2 wt%
0.2% by weight triethanolamine
Preservative 0.05 wt%
0.05% by weight of pigment
0.05% by weight fragrance
Purified water to 100%
Claims (21)
The extract of Mohwangryun Extract is an extract obtained by extracting Mohwangryun with at least one selected from the group consisting of water and an organic solvent.
The organic solvent may be a polar solvent containing a lower alcohol having 1 to 5 carbon atoms, ethyl acetate, or acetone; A nonpolar solvent comprising ether, chloroform, benzene, hexane or dichlorohexane; Or a mixed solvent thereof.
Wherein the composition is for the manufacture of a medicament for skin regeneration, a cosmetic preparation or a food product.
Wherein the composition is for the manufacture of a medicament for the enhancement of skin elasticity or wrinkle, a cosmetic preparation or a food product.
Wherein the composition is for skin whitening medicines, cosmetics or foods.
Wherein the composition is for the production of antioxidant medicines, cosmetics or foods.
Wherein the composition is for the manufacture of an anti-inflammatory medicament, a cosmetic or food product.
Wherein the composition is for the manufacture of a medicament for the improvement of atopy, a cosmetic preparation or a food product.
Wherein the composition is for skin moisturizing medicines, cosmetics or foods.
Wherein the composition is for the manufacture of a medicament for the improvement of skin texture, a cosmetic preparation or a food product.
Wherein the composition is for promoting stem cell proliferation or stem cell retention.
Wherein the composition is for the production of a cosmetic for promoting stem cell activity.
Priority Applications (1)
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Applications Claiming Priority (1)
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KR1020150121692A KR20170025351A (en) | 2015-08-28 | 2015-08-28 | Composition for improving skin |
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Family
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Country Status (1)
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KR (1) | KR20170025351A (en) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH08208424A (en) | 1994-12-20 | 1996-08-13 | Unilever Nv | Cosmetic composition containing betulinic acid |
JPH08231370A (en) | 1995-02-23 | 1996-09-10 | Taiyo Kagaku Co Ltd | Skin cosmetic |
JPH0940523A (en) | 1995-07-28 | 1997-02-10 | Ichimaru Pharcos Co Ltd | Fibroblast proliferation promoter containing water extract form chlorella |
JPH1036283A (en) | 1996-07-18 | 1998-02-10 | Ichimaru Pharcos Co Ltd | Fibroblast proliferation promoting agent |
-
2015
- 2015-08-28 KR KR1020150121692A patent/KR20170025351A/en unknown
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH08208424A (en) | 1994-12-20 | 1996-08-13 | Unilever Nv | Cosmetic composition containing betulinic acid |
JPH08231370A (en) | 1995-02-23 | 1996-09-10 | Taiyo Kagaku Co Ltd | Skin cosmetic |
JPH0940523A (en) | 1995-07-28 | 1997-02-10 | Ichimaru Pharcos Co Ltd | Fibroblast proliferation promoter containing water extract form chlorella |
JPH1036283A (en) | 1996-07-18 | 1998-02-10 | Ichimaru Pharcos Co Ltd | Fibroblast proliferation promoting agent |
Non-Patent Citations (8)
Title |
---|
Cardinale G. et al, Adv. Enzymol., 41, p. 425, 1974 |
Epidermal Stem Cells of the Skin, Cedric Blanpain, Elaine Fuchs, Annual Review of Cell and Developmental Biology, November 2006, Vol. 22, Pages 339-373 |
Feingold 외, J. Invest. Dermatol., 110, pp 368-375, 1998. |
Feingold 외, J. Invest. Dermatol., 115, pp 353-360, 2000. |
Human skin stem cells and the ageing process, Catherin Niemann, Stem Cell Aging and Regenerative Medicine, November 2008, Pages 986-997 |
Journal of the European Academy of Dermatology and Venereology. 12:103-114, 1999 |
Skin research and technology.5:189-194, 1999 |
The British journal of dermatology. 110: 129-138, 1984 |
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