KR20170080090A - Composition for improving skin conditions comprising eupalinolide A - Google Patents
Composition for improving skin conditions comprising eupalinolide A Download PDFInfo
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- KR20170080090A KR20170080090A KR1020150191294A KR20150191294A KR20170080090A KR 20170080090 A KR20170080090 A KR 20170080090A KR 1020150191294 A KR1020150191294 A KR 1020150191294A KR 20150191294 A KR20150191294 A KR 20150191294A KR 20170080090 A KR20170080090 A KR 20170080090A
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- skin
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- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
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- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
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- A—HUMAN NECESSITIES
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- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
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Landscapes
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Abstract
The present invention relates to a cosmetic composition, a pharmaceutical composition and a health food which have excellent effects on skin antihalation, wrinkle improvement or elasticity improvement. The composition of the present invention exhibits excellent effects on skin elasticity enhancement, skin wrinkle improvement, or skin moisturization. The compound of Chemical Formula (1), which is an active ingredient of the composition of the present invention, can be used as a cosmetic raw material, a pharmaceutical ingredient or a health food raw material which is safe for skin and has excellent skin condition improving effect.
Description
More particularly, the present invention relates to a cosmetic composition, a pharmaceutical composition, and a health food which have excellent effects on skin antihalation, wrinkle improvement or elasticity improvement.
Collagen is a major substrate protein produced in the fibroblasts of the skin and exists in extracellular epilepsy. Its important functions are mechanical durability of the skin, resistance of connective tissues and binding force of tissues, support of cell adhesion, cell division and differentiation (Induction of growth of an organism or wound healing) are known. Such collagen is reduced by photoaging by age and ultraviolet irradiation, and collagenase activity, which degrades collagen, promotes collagen reduction. This is known to be closely related to the formation of wrinkles in the skin.
In addition, Elastin fiber forms crosslinks with collagen and is a skin constituent important for wrinkle formation involved in skin elasticity. The deficiency and aggregation of elastin fibers and the marked increase in the activity of the elastin degrading enzyme Elastase have been found to be one of the causes of skin wrinkles. It is known that Elastase is the only enzyme capable of degrading elastin, and its inhibition can fundamentally reduce the wrinkles of the skin.
On the other hand, collagen and elastin fibers are substrate proteins that play an important role in water retention in the dermal layer. These protein proteins adsorb moisture and increase the water holding capacity inside the structure, thereby allowing the skin to maintain proper moisture content. And it is known to be involved in maintaining the elasticity of the skin.
In addition, the elastic fiber produced in the fibroblast of the skin forms a cross-link with collagen, and is a skin constituent important for wrinkle formation which is involved in skin elasticity. Deficiency and decomposition of elastic fibers were found to be one of the main factors of skin wrinkle formation and elasticity reduction.
Presently, retinoids, adenosine, animal placenta-derived proteins, chlorella extract, and the like are known to improve wrinkles. The best known retinol promotes collagen synthesis and inhibits elastase enzymes, but it is unstable. When applied to the skin, it has a limited use due to safety problems such as irritation and redness, and chlorella extract has little effect, It is known that it is difficult to expect a wrinkle-improving effect.
Glycation generally refers to a reaction in which a simple sugar such as glucose or fructose forms a covalent bond to a protein or fat that occurs without involvement of the enzyme. Saccharification takes place through a series of complex chemical reactions known as Amadori rearrangement, Maillard reaction, which results in the formation of advanced glycation endproducts (AGEs).
On the other hand, the glycation process of the protein does not involve the enzymatic action, so it occurs slowly, and as a result, the protein having a longer half-life such as collagen has more influence. Analysis of the final glycation products revealed that the more aged the glycated collagen was accumulated, the accumulation of the final glycated product changed the protein to a harder and more brittle state, and the glycated collagen was found in the extracellular matrix of the dermal layer (Dyer, DG et al. , The Journal of Clinical Investigation, 9, p. 2463, 1993), by inhibiting collagen from forming a proper structure and thereby reducing skin elasticity and promoting wrinkle formation.
Also, it is known that the final saccharification product produced by saccharification is a brownish substance and accumulates on the dermal layer as the skin ages. It is believed that as the aging of the skin progresses gradually, the face light turns yellow and it is known that the reflection light reflected from the skin decreases as the specific final saccharification product accumulates. While the amount of melanin pigment in the skin is weakly related to skin aging, the final glycation product accumulated in the dermal layer of the skin gradually increases in amount as the skin ages, and the skin color becomes dull (Hiroshi, O. et al . Skin Research and Technology, 15, p. 496, 2009).
Aminoguanidine, pyridoxamine, and aspirin are known to inhibit glycosylation. However, these substances are limited in their use due to the safety of the skin, There is a problem that can not be expected.
Accordingly, it is desired to provide a composition which is safe in the living body, has an effective component that is safe to the skin and has high stability, and most of all has antihalation, wrinkle improvement or elasticity improvement effect in skin. Development is urgently required.
Therefore, a problem to be solved by the present invention is to solve the above-mentioned problems, and to provide a new active ingredient which is low in side effects and safe to human body and excellent in skin antihalation, wrinkle improvement or elasticity improvement effect, .
In other words, a problem to be solved by the present invention is to provide a composition comprising an active ingredient having excellent efficacy as an active ingredient.
In order to solve the above problems, the present invention provides a composition for enhancing skin elasticity, for improving wrinkles of skin or for moisturizing skin comprising Eupalinolide A as an active ingredient, preferably a cosmetic composition, Provide health food.
That is, the present invention provides a new use for the skin elasticity enhancement, the skin wrinkle improvement, or the skin moisturization of yupallinolide a.
The inventors of the present invention have found that yupallinolide ai promotes skin collagen production and inhibits the activity of elastase, thereby improving the wrinkles and elasticity of the skin, thus completing the present invention. In addition, the yupallinolide ai exhibits an antihyperglycosylation effect, and acts as an auxiliary to improve skin wrinkles and skin elasticity, thus exhibiting a synergistic effect.
In the present invention, the term 'improving elasticity or skin elasticity' means reducing the degree to which the skin is stuck or stretched. In addition, the elasticity means that elasticity of the skin is maintained in a state where elastin and collagen are sufficiently present.
In the present invention, "improving wrinkles" refers to preventing, suppressing or inhibiting the generation of wrinkles on the skin, or alleviating wrinkles that have already been formed.
In the present invention, the term 'moisturizing or skin moisturizing' means increasing the skin moisture and maintaining a moist state. Skin moisturizing effect can help to improve wrinkles and elasticity of skin.
In the present invention, the 'antagonism' effect means preventing the collagen from being saccharified in the extracellular matrix of the dermal layer, thereby enhancing elasticity of the skin and preventing wrinkle formation. That is, in the present invention, the antihyperglycosylation effect may cause a synergistic effect on skin elasticity enhancement and wrinkle improvement.
In order to solve the above-mentioned problems and to achieve the object of the present invention, the present invention provides a composition comprising a compound represented by the following general formula (1).
[Chemical Formula 1]
The compound represented by the formula (1) has a molecular formula C 24 H 30 O 9 , a molecular weight of 462.4896, and is named Eupalinolide A.
The present invention is not particularly limited to the method for obtaining the above-mentioned yupallinolide ai, and can be chemically synthesized by a known method in the field of the present invention, or a commercially available material can be used.
In the cosmetic composition, the pharmaceutical composition and the health food according to the present invention, the content of the yupallinolide ame is preferably 0.00001 to 10% by weight relative to the total weight of the cosmetic composition, the pharmaceutical composition and the health food.
The eupholinolide a of the present invention may exist in solvated as well as unsolvated forms, including forms such as hydrates, ethoxylates, and the like. The yulpalinolide a of the present invention may exist in a crystalline or amorphous form, and all such physical forms are included within the scope of the present invention.
The composition for skin elasticity enhancement, skin wrinkle improvement or skin moisturizing composition according to the present invention can be used as a solution for ointment, external ointment, cream, foam, nutrition lotion, softening water, pack, soft water, lotion, makeup base, essence, From a group consisting of a bath, a sunscreen cream, a sun oil, a suspension, an emulsion, a paste, a gel, a lotion, a powder, a soap, a surfactant-containing cleansing oil, a powder foundation, an emulsion foundation, a wax foundation, But are not limited thereto.
In addition, the cosmetic composition of the present invention may further comprise at least one cosmetically acceptable carrier compounded in a cosmetic composition for general skin, and examples thereof include oil, water, a surfactant, a moisturizer, a lower alcohol, A thickening agent, a chelating agent, a coloring matter, an antiseptic, a perfume, and the like may be appropriately compounded, but the present invention is not limited thereto.
The cosmetically acceptable carrier contained in the cosmetic composition of the present invention varies depending on the formulations. When the formulation of the present invention is an ointment, a paste, a cream or a gel, the carrier component may be an animal oil, a vegetable oil, a wax, a paraffin, a starch, a tracer, a cellulose derivative, polyethylene glycol, silicon, bentonite, silica, talc, zinc oxide Mixtures of these may be used.
When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder or a mixture thereof may be used as the carrier component, Propellants such as fluorohydrocarbons, propane / butane or dimethyl ether.
When the formulation of the present invention is a solution or an emulsion, a solvent, a solubilizing agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl benzoate, -Butyl glycol oil, and in particular fatty acid esters of cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerol aliphatic esters, polyethylene glycols or sorbitan.
When the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspension such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Crystalline cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.
When the formulation of the present invention is a soap, alkali metal salts of fatty acids, fatty acid hemiesters, fatty acid protein hydrolizates, isethionates, lanolin derivatives, aliphatic alcohols, vegetable oils, glycerol, sugars and the like are used as carrier components .
The present invention also provides a skin elasticity enhancement, skin wrinkle improvement or skin moisturizing method comprising the step of applying the compound represented by the above formula (1) to the individual's skin. The subject includes, without limitation, mammals including rats, livestock, humans, and the like.
According to another embodiment of the present invention, there is provided a pharmaceutical composition for improving skin elasticity, improving skin wrinkles or moisturizing skin, which comprises the compound of formula (1) as an active ingredient.
The composition comprising the compound of the present invention may be various oral or parenteral formulations, but may preferably be a parenteral agent. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like are also used. Liquid preparations 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. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, and emulsions. 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.
The present invention can also be provided as a formulation for external skin application for skin elasticity enhancement, skin wrinkle improvement or skin moisturizing comprising the compound of formula (1) as an active ingredient.
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.
The pharmaceutical composition of the present invention is particularly preferably used as a parenteral preparation. For example, the external preparation for skin may be a pharmaceutically acceptable base such as vaseline or stearyl alcohol; Suitable pharmaceutically acceptable surfactants such as polysorbate, sorbitan sesquioleate, and the like; A suitable pharmaceutically acceptable humectant such as glycerin; A suitable pharmaceutically acceptable solvent; And a conventional external preparation for skin preparation in which a flavoring agent, a coloring agent, a stabilizer, a tackifier and the like are homogeneously mixed.
When the compound of Chemical Formula 1 of the present invention is used as a medicine, it may further contain one or more active ingredients showing the same or similar functions. For example, it may contain known components for skin elasticity enhancement, skin wrinkle improvement, or skin moisturizing. The skin elasticity enhancement, skin wrinkle improvement or skin moisturizing effect of the composition of the present invention may be further enhanced if the skin elasticity enhancing agent, the skin wrinkle improving agent or the skin moisturizing agent is included. 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 elasticity or wrinkle improving ingredient known in the art and includes retinoic acid, TGF, animal placenta-derived proteins, betulinic acid and chlorella extract; Examples of moisturizing ingredients known in the art include petrolatum, mineral oil, silicone, triglycerides, essential fatty acids such as gamma linolenic acid (evening primrose oil), GGF, amino acids, provitamin B5, hyaluronic acid, γ-glutamic acid, Lipidure PMB, ceramide, cholesterol, fatty acids; And derivatives thereof, and various plant extracts. ≪ Desc / Clms Page number 2 > The additional ingredients may be included in an amount of 0.0001 to 10% by weight based on the total weight of the composition, and the content may be adjusted according to requirements such as skin safety, ease of formulation of the compound of Formula 1, and the like.
The pharmaceutical composition of the present invention can provide skin elasticity enhancement, skin wrinkle improvement or skin moisturizing effect when the compound of Formula 1 is contained in an effective amount. In the present invention, the term "effective amount" means the amount of a compound capable of sufficiently exhibiting skin elasticity enhancement, skin wrinkle improvement, or skin moisturizing 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 commercialized as a pharmaceutical product, the compound of Formula 1 may be contained at a higher concentration than that of a cosmetic product that is routinely applied to 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.
According to still another embodiment of the present invention, there is provided a health food for skin elasticity enhancement, skin wrinkle improvement or skin moisturization comprising the compound of formula (1).
The term 'health food' as used herein means a food prepared by adding the compound of formula (1) to food materials such as beverage, tea, spice, gum and confectionery, or by encapsulation, powdering or suspension, But it has the advantage that there are no side effects that can occur when a drug is used for a long period of time using a food as a raw material. The health food of the present invention obtained in this way can be taken on a daily basis and is thus very useful because it can be expected to exert excellent effects on skin elasticity enhancement, skin wrinkle improvement or skin moisturization.
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 the food to which the above substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include health foods in a conventional sense. The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. 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 health food of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, , A carbonating agent used in carbonated drinks, and the like. In addition, the health food of the present invention may contain flesh for the production of natural fruit juice, fruit juice drink and vegetable drink. 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.
In one embodiment of the present invention, the composition may contain 0.00001 wt% to 10 wt% of the compound of Formula 1 based on the weight of the entire composition.
The composition containing the euphiolinoidoe of the present invention exhibits excellent effects on skin elasticity enhancement, skin wrinkle improvement or skin moisturization.
The composition containing the yupallinolide A of the present invention can be used as a raw material for cosmetics, a pharmaceutical ingredient, or a health food, which is safe for skin and has excellent skin condition improving effect.
Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the embodiments described below. The embodiments of the present invention are provided by way of example to facilitate a specific understanding of the present invention.
Reference Example One: Yupalinolide a( Eupalinolide A) Material information
[Chemical Formula 1]
Material name: Eupalinolide A
CAS No. : 877822-41-8
Molecular formula: C 24 H 30 O 9
Molecular weight: 462.4896
Where to buy: Shanghai Tauto Biotech Co., Ltd
Experimental Example 1: promoting the synthesis of type I collagen in human fibroblasts
The compound of Chemical Formula 1 was added to the culture medium of human-derived fibroblasts to confirm the promoting effect of type I collagen synthesis at the cellular level. The synthesized collagen was quantitated using a PICP EIA kit (Procollagen Type I C-Peptide Enzyme Immuno Assay Kit). To measure the amount of collagen synthesis, the compound of formula (1) was added to a culture medium of fibroblasts (DMEM medium) and cultured for 48 hours. The culture broth was taken and the degree of type 1 collagen synthesis was measured by a PICP EIA kit using a spectrophotometer And measured at 450 nm.
For the comparison of the effects, the degree of collagen synthesis was measured in the same manner for the samples in which the culture medium of the untreated fibroblasts (negative control) and vitamin C (positive control) were added to a final concentration of 52.85 / / ml. The increase rate of collagen production was calculated as a ratio of relative collagen production to the control group, and the results are shown in Table 1 below.
Promoting collagen synthesis of the compound of formula (1) (number of repeats = 4)
(Vitamin C, 52.85ppm)
As can be seen from the results of Table 1, when the compound of Chemical Formula 1 was treated, the amount of collagen synthesis was increased in a concentration-dependent manner. In the case of vitamin C, which is generally known to induce collagen synthesis, Synthesis effect.
Experimental Example 2: Ella Stays Active inhibitory effect
The activity inhibitory effect of Elastase, an enzyme that degrades elastin, was confirmed as follows.
Elastase used Elastase from human leukocyte cells and MeOSuc-Ala-Ala-Pro-Val-pNA as synthetic substrate for Elastase. The buffer solution used was 100 mM Tris (pH 7.5) solution. Finally, 0.2 mU was used for the ELASTASES using a buffer solution. In addition, the synthetic substrate of Elastase was diluted with buffer solution to make a final concentration of 0.5 mM by making a 100 mM solution using DMSO. At this time, the positive control group was set to contain 10 ppm of quercetin, which is known as an ELASTIC inhibitor. Ella stase inhibition candidates were added to give a final concentration of 10, 20 ppm. The reaction was carried out in a 96-well plate and allowed to react at room temperature for 20 minutes. Absorbance was measured at 405 nm using a spectrophotometer at intervals of 1 minute, and the slope of the absorbance versus time was determined as the activity of the enzyme. Ella stasis inhibition rates were calculated as follows.
Elastase activity inhibitory effect (number of repeats = 3) of the compound of formula (1)
As can be seen from the results in Table 2, the compound of Chemical Formula 1 showed a somewhat lower inhibitory effect on the enzyme activity at a concentration of 10 ppm compared to the positive control, quercetin. However, at a concentration of 20 ppm, And the compound of the formula (1) was found to be excellent in the effect of inhibiting the enzyme activity. Thus, it has been found that the compound of formula (I) can be effectively used for skin elasticity and wrinkle improvement.
Experimental Example 3: Glycation The anti- glycation ) effect
In order to confirm the anti-glycation effect, the saccharification inhibitory activity was measured using L-arginine and glucose.
First, 1 M L-arginine and 1 M glucose were prepared by dissolving 1 M phosphoric acid buffer (pH 7.4) and diluted to 50 ppm and 100 ppm using 1M phosphate buffer solution. 1M L-arginine and 1M phosphate buffer solution were mixed at a ratio of 1: 4, and then 80 [mu] l each was added to a 96-well plate. To each sample, 100 μl of 0.01 M aminoguanidine to be used as a positive control and a sample diluted to 50 ppm and 100 ppm, respectively, were added. These samples were mixed well and finally glucose diluted with 1M phosphate buffer solution was added to the final concentration of glucose to 0.1 M and reacted at 70 ° C for 4 hours. The degree of saccharification was measured by measuring the absorbance of the 96-well plate at 420 nm using a spectrophotometer.
Glycation group of the following formula was an experimental group in which 1M L-arginine and 1M glucose were added to induce glycation. Absorbance was measured at 420 nm by adding 1M L-arginine and sample alone without glucose to measure the absorbance of the sample itself. The saccharide inhibitory activity can be obtained by the following formula.
The antagonism effect of the compound of formula (1)
As can be seen from the results shown in Table 3, the compound of Chemical Formula 1 was found to be more excellent in antagonism effect as compared with aminoguanidine known as an antagonist. That is, the compound of the formula (1) exhibits an excellent antihyperglycosylating effect, and antiherating effect plays an auxiliary role in improving the wrinkles and elasticity of the skin, and a synergistic effect can be expected.
Claims (6)
[Chemical Formula 1]
[Chemical Formula 1]
[Chemical Formula 1]
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| KR1020150191294A KR20170080090A (en) | 2015-12-31 | 2015-12-31 | Composition for improving skin conditions comprising eupalinolide A |
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| KR1020150191294A KR20170080090A (en) | 2015-12-31 | 2015-12-31 | Composition for improving skin conditions comprising eupalinolide A |
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