KR20160128764A - Composition for improving skin - Google Patents
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- KR20160128764A KR20160128764A KR1020150060634A KR20150060634A KR20160128764A KR 20160128764 A KR20160128764 A KR 20160128764A KR 1020150060634 A KR1020150060634 A KR 1020150060634A KR 20150060634 A KR20150060634 A KR 20150060634A KR 20160128764 A KR20160128764 A KR 20160128764A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4913—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
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Abstract
The present invention relates to a composition for improving skin. Indirubin according to the present invention can be used for skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening and skin tone improvement pharmacology, cosmetic treatment for improving skin elasticity by promoting collagen synthesis, melanin synthesis promoting effect, , Food or skin external preparation formulations. In addition, it promotes proliferation of dermal stem cells and exhibits a stem cell-retaining effect, and thus can be used for the production of cosmetic formulations for promoting stem cell activity.
Description
The present invention relates to a skin improving composition exhibiting skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, 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. In addition, 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 Literature 5]. 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 6]. 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, various phenomena of skin aging can be improved through the activation of stem cells [Non-Patent Document 7].
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.
Accordingly, the present inventors have found that Indirubin promotes collagen synthesis of fibroblasts of the skin and promotes proliferation of skin stem cells to promote skin regeneration, improve wrinkles, improve elasticity, inhibit melanin synthesis, The present invention has been accomplished by confirming the effect of stimulating stem cell activity by promoting the proliferation of skin stem cells and exhibiting stem cell maintenance effect in addition to skin texture improving effect due to improvement of skin brightness.
Accordingly, an object of the present invention is to provide a composition for skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening and skin texture improvement, which comprises a compound represented by the following formula 1 as an active ingredient:
[Chemical Formula 1]
Another object of the present invention is to provide a composition for stimulating stem cell activity comprising a compound represented by the following formula (1) as an active ingredient:
[Chemical Formula 1]
As a means for solving the above-mentioned problems, the present invention provides a method for skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening and skin whitening comprising a compound represented by the following formula (1) as an active ingredient for the manufacture of pharmaceutical, cosmetic, A composition for improving skin texture is provided:
[Chemical Formula 1]
As another means for solving the above problems, the present invention provides a composition for promoting stem cell activity comprising, as an active ingredient, a compound represented by the following formula (1) for the production of a cosmetic formulation:
[Chemical Formula 1]
Indirubin according to the present invention promotes collagen synthesis of fibroblasts of the skin and promotes proliferation of skin stem cells to promote skin regeneration, improve wrinkles, improve elasticity, inhibit melanin synthesis, And exhibits an effect of improving the skin texture due to the improvement of the skin brightness, so that it can be used in the manufacture of pharmaceuticals, cosmetics, food or skin external preparation formulations.
In addition, Indirubin 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 elasticity, whitening skin, and improve skin texture, it is necessary to improve skin regeneration, wrinkle improvement, elasticity improvement, skin whitening and skin tone improving activity at low concentration And is low in volatility so as to be able to stay for a sufficient time to exhibit skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening and skin texture improving effect, and the active ingredient is stable And it is easy to formulate into pharmacy, cosmetics, food, skin external agent and the like, and it is preferable that it is safe for skin. 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 and skin tone improving ingredients are excellent in skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening and skin tone improving activity even at low concentration in in vitro test, It is difficult to apply to real skin because of its ability to permeate and absorb. Other active ingredients have low hydrophilicity, making them difficult to formulate into medicines, cosmetics, and foods. In addition, some skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, and skin tone improvement components may be decomposed or otherwise converted to other compounds when exposed to heat, light, or oxygen, There are also cases.
As can be seen from the following examples, indirubin exhibits excellent collagen synthesis promotion effect, melanin formation inhibition effect and skin brightness improvement effect at a low concentration, so that skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, Cosmetics, food, skin external agent, and the like.
Accordingly, the present invention provides a composition for improving skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening, and skin texture improvement comprising a compound represented by the following formula (1) as an active ingredient.
[Chemical Formula 1]
The compound of Chemical Formula 1 is named 3- (1,3-dihydro-3-oxo-2H-indol-2-ylidene) -1,3-dihydro-2H- 1,3-dihydro-3-oxo-2H-indol-2-ylidene) -1,3-dihydro-2H-indol-2-one] and is also called indirubin.
The compound of formula (1) may be synthesized or a commercially available compound may be used.
The compositions of the present invention may be used for the manufacture of pharmaceutical formulations.
Accordingly, the composition of the present invention may comprise a pharmaceutically acceptable salt of the compound of formula (1).
The pharmaceutically acceptable salt of the compound of Formula 1 may be an acid addition salt formed using an organic acid or an inorganic acid, and the organic acid may be, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid The organic acid may be selected from the group consisting of hydrochloric acid, hydrobromic acid, hydrochloric acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic acid, , Benzenesulfonic acid, p-toluenesulfonic acid and methanesulfonic acid-based salts, and the inorganic acid includes, for example, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid and boric acid-based salts. Preferably in the hydrochloride or acetate form, more preferably in the hydrochloride form.
The above-mentioned acid addition salts may be obtained by a) directly mixing the compound of formula 1 and an acid, or b) dissolving and mixing one of them in a solvent or a water solvent, or c) Lt; RTI ID = 0.0 > acid < / RTI > in a solvent and mixing them.
In addition to the above, additionally saltable forms include, but are not limited to, the salts of gabapentin, pregabalin, nicotinate, adipate, hemimarate, cysteine, acetylcysteine, methionine, arginine, Aspartate and the like.
The composition may further contain one or more active ingredients exhibiting the same or similar functions. For example, it may contain known skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening and skin tone improving ingredients. Wrinkle improvement, skin elasticity enhancement, skin whitening, and skin tone improving composition, the effect of the composition of the present invention on skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening 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 invention, the composition is a skin regeneration component known in the art, including retinoic acid, TGF, animal placenta-derived protein, betulinic acid and chlorella extract, (Hydroquinone), vitamin-C (L-ascorbic acid) and derivatives thereof, and various plant extracts, such as kojic acid and arbutin, Or may further comprise two or more components. The additional component may be included 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, ease of formulation of the compound of Formula 1 .
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, which may be formulated with the composition of the present invention in combination with at least one excipient such as starch, calcium carbonate, (Sucrose), lactose, gelatin and the like.
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 restoration of skin tissue against damage caused by external or internal causes of the skin. Damage due to external causes may include ultraviolet rays, external contaminants, wound, trauma, etc. The damage caused by the internal causes 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 " 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" means an amount of a compound capable of promoting regeneration of damaged skin, improving wrinkles, improving elasticity, exhibiting a whitening effect, or improving skin texture. When the composition of the present invention contains an effective amount of the compound of Formula 1, it is possible to provide desirable skin regeneration effect, wrinkle improving effect, elasticity improving effect, skin whitening effect and skin texture improving effect. An effective amount of the compound of formula (1) contained in the composition of the present invention will vary depending on the form in which the composition is commercialized, how the compound is applied to the skin, and the time on the skin. For example, when the composition is produced into a pharmaceutical formulation, it may contain the compound of Formula 1 at a higher concentration than when it is commercialized as cosmetics that are routinely applied to the skin. Accordingly, the daily dosage is 0.1 to 100 mg / kg, preferably 30 to 80 mg / kg, more preferably 50 to 60 mg / kg, based on the amount of the compound of formula (1) 6 times a day.
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.
Further, the composition for improving skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening and skin texture improvement of the present invention can be used for the preparation of external preparation for skin.
When the compound of formula (1) is used as an external preparation for skin, it may further comprise at least one selected from the group consisting of fatty substances, organic solvents, solubilizers, thickeners and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, , Water, ionic or nonionic emulsifiers, fillers, sequestering agents and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or external preparations for skin And any other ingredients used in the skin sciences. The components can also be introduced in amounts commonly used in the field of dermatology.
When the compound of Formula 1 is provided as an external preparation for skin, it may have a formulation such as, but not limited to, ointments, patches, gels, creams or sprays.
Further, the composition for improving skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening 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.
The cosmetic composition may further contain, in addition to the compound of Formula 1, a lipid, 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, , Ionic or nonionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, barrier agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or cosmetics And may contain adjuvants commonly used in the cosmetics field, such as any of the other ingredients.
The cosmetic formulation may contain a relatively high concentration of the compound of formula (1) in the case of a wash-off type cosmetic such as a makeup 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, etc., in which the active ingredient remains on the skin for a long period of time, It may be included. In one embodiment of the present invention, although not limited thereto, the composition may contain 0.0001 wt% to 10 wt% (preferably 0.0001 wt% to 1 wt%) of the compound of Formula 1 based on the total weight of the composition . When the composition of the present invention contains less than 0.0001% by weight of the compound of the formula 1, sufficient skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening and skin texture improving effect can not be expected, In this case, it is intended to prevent an allergic reaction such as an unwanted reaction or a skin safety problem.
Further, the composition for improving skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening and skin texture improvement of the present invention can be used for manufacturing food formulations.
The food formulation refers to food prepared by adding the compound of Formula 1 to food materials such as beverage, tea, spice, gum, confectionery, etc., or by encapsulation, powdering, suspension or the like.
Since the food preparation can be routinely ingested, it is very useful because high skin regeneration, wrinkle improvement, elasticity enhancement, skin whitening and skin texture improving effect can be expected.
When the compound of Chemical Formula 1 is used as a food additive, the compound of Chemical Formula 1 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 promoting stem cell activity comprising the compound of Formula 1 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, 'stem cell activity promoting effect' refers to a stem cell proliferation promoting effect and / or a stem cell maintaining effect.
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 compound of formula (1).
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.
Reference Example One: Indy Rubin ( Indirubin ) Material information
[Chemical Formula 1]
CAS No .: 479-41-4
Where to buy: Sichuan Hongjie Import & Export CO., LTD
Reference Example 2: Serum-free Under medium conditions Cultivation of dermal stem cells
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). Thereafter, the culture medium was removed through a suction tube, and the medium was removed using a PBS solution (GibcoBRL). 1 / / mL of the compound of the formula (1) was treated with CNT-57 medium containing no BPE, 2 and 37 < 0 > C for 72 hours.
Experimental Example One: CCK Promoting the proliferation of skin stem cells through the -8 evaluation method
The skin stem cells cultured in Reference 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. The proliferation rate (%) of the compound of the formula (1) was determined from the measured absorbance value according to the following equation (1) with respect to the control group (CNT-57 medium supplemented with BPE) .
[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 condition treated with the compound of the formula (1) showed an excellent proliferation promoting effect.
Experimental Example 2: Stem Cellularity of Dermal Stem Cells 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 Reference 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 condition treated with the compound of Formula 1 promotes the expression of p63 in dermal stem cells, and thus has excellent stem cell retention effect.
Example 1: Promoting collagen synthesis
The compound of Chemical Formula 1 was added to the culture medium of human fibroblasts to examine the effect of promoting collagen synthesis at the cellular level. The biocompatible collagen was quantitated using a PICP EIA kit (Procollagen Type I C-Peptide Enzyme Immunoassay Kit).
The compound of formula (1) was added to the culture medium of human fibroblasts (7 x 10 4 cells / cm 2 ) together with vitamin C and a control (no addition) to give final concentrations of 10 μg / mL and 20 μg / After culturing for 1 day, the culture broth was taken and the degree of collagen biosynthesis at each concentration was measured at 450 nm using a spectrophotometer with 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 compound of Chemical Formula 1 has excellent collagen synthesis ability against human-derived fibroblasts, and has 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
The compound of Chemical Formula 1 was added to the culture of mouse melanoma cell (B-16 mouse melanoma cell) to test the whitening effect at the cellular level (Lotan R., Lotan D. Cancer Res. 40: 3345-3350, 1980 ). 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 compound of Chemical Formula 1 was added to the culture medium to a final concentration of 10 μg / mL and 20 μg / mL, and the control group, arbutin, was added to the medium to a concentration of 200 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, the compound of formula (I) has remarkably superior melanin production inhibitory activity against melanoma cells of rat melanoma cells cultured in comparison with albutin, which is a known whitening substance.
Example 3: To improve the turn-over of the skin About 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 5 below.
As shown in Table 5, 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: Preparation of pharmaceutical preparations
1. Preparation of tablets
0.2 mg of the compound of formula (1)
100 mg of corn starch
100 mg of milk
Stearic acid Magnesium 2 mg
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
A nutritional cream containing the compound of formula (1) as an active ingredient was prepared according to a conventional method, as shown below.
0.2% by weight of the compound of formula (1)
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
An ointment containing the compound of formula (I) as an active ingredient was prepared according to a conventional method, as shown below.
0.5% by weight of the compound of formula (1)
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 (11)
[Chemical Formula 1]
A composition for skin regeneration or wrinkle improvement, wherein the composition is for the manufacture of a pharmaceutical, cosmetic, food or external preparation for skin regeneration or wrinkle improvement.
[Chemical Formula 1]
Wherein the composition is for the preparation of a pharmaceutical composition for promoting skin elasticity, a cosmetic composition, a food or an external preparation for skin.
[Chemical Formula 1]
Wherein the composition is for the preparation of a skin whitening pharmacy, cosmetic, food, or external preparation for skin.
[Chemical Formula 1]
Wherein the composition is for the manufacture of a pharmaceutical, cosmetic, food or skin topical formulation for improving skin texture.
[Chemical Formula 1]
Wherein the composition is for promoting stem cell proliferation or stem cell retention.
Wherein the composition is for the production of a cosmetic preparation for promoting stem cell activity.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150060634A KR20160128764A (en) | 2015-04-29 | 2015-04-29 | Composition for improving skin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150060634A KR20160128764A (en) | 2015-04-29 | 2015-04-29 | Composition for improving skin |
Publications (1)
| Publication Number | Publication Date |
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| KR20160128764A true KR20160128764A (en) | 2016-11-08 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| KR1020150060634A KR20160128764A (en) | 2015-04-29 | 2015-04-29 | Composition for improving skin |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020009503A1 (en) * | 2018-07-06 | 2020-01-09 | 주식회사 씨케이바이오텍 | Pharmaceutical composition comprising indirubin derivative as active ingredient |
| KR20200005188A (en) * | 2018-07-06 | 2020-01-15 | 주식회사 씨케이바이오텍 | composition for preventing or treating of wound comprising Indirubin derivative compound |
| JP2021523156A (en) * | 2018-05-07 | 2021-09-02 | マイケル アインジガー， | A photoprotective composition containing a compound derived from Malassezia and / or a chemical analog thereof. |
| US11202748B2 (en) * | 2018-08-24 | 2021-12-21 | Versicolor Technologies, Llc | Photoprotective compositions containing malassezia-derived compounds and/or chemical analogs thereof |
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 |
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2015
- 2015-04-29 KR KR1020150060634A patent/KR20160128764A/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., vol. 41, pp. 425, 1974 |
| Epidermal Stem Cells of the Skin, Cedric Blanpain, Elaine Fuchs, Annual Review of Cell and Developmental Biology, November, vol. 22, pp. 339-373, 2006 |
| Feingold 외, J. Invest. Dermatol., vol. 110, pp. 368-375, 1998 |
| Feingold 외, J. Invest. Dermatol., vol. 115, pp. 353-360, 2000 |
| Human skin stem cells and the ageing process, Catherin Niemann, Stem Cell Aging and Regenerative Medicine, pp. 986-997, 2008. 11 |
| Journal of the European Academy of Dermatology and Venereology, vol. 12, pp. 103-114, 1999 |
| Skin research and technology, vol. 5, pp. 189-194, 1999 |
| The British journal of dermatology, vol. 110, pp. 129-138, 1984 |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2021523156A (en) * | 2018-05-07 | 2021-09-02 | マイケル アインジガー， | A photoprotective composition containing a compound derived from Malassezia and / or a chemical analog thereof. |
| WO2020009503A1 (en) * | 2018-07-06 | 2020-01-09 | 주식회사 씨케이바이오텍 | Pharmaceutical composition comprising indirubin derivative as active ingredient |
| KR20200005188A (en) * | 2018-07-06 | 2020-01-15 | 주식회사 씨케이바이오텍 | composition for preventing or treating of wound comprising Indirubin derivative compound |
| CN112334131A (en) * | 2018-07-06 | 2021-02-05 | Ck生物技术公司 | Pharmaceutical composition comprising indirubin derivative as active ingredient |
| US11773081B2 (en) | 2018-07-06 | 2023-10-03 | Ck Regeon Inc. | Pharmaceutical composition for preventing or treating wound, comprising indirubin derivative as active ingredient |
| CN112334131B (en) * | 2018-07-06 | 2024-04-05 | Ck生物技术公司 | Pharmaceutical composition comprising indirubin derivative as active ingredient |
| US11202748B2 (en) * | 2018-08-24 | 2021-12-21 | Versicolor Technologies, Llc | Photoprotective compositions containing malassezia-derived compounds and/or chemical analogs thereof |
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