KR20200094513A - Composition for promoting collagen synthesis comprising albiflorin as an effective ingredient - Google Patents

Abstract

A composition for promoting collagen synthesis is disclosed in the present specification. In one aspect, an active ingredient of the present invention, albiflorin, a salt, isomer, hydrate or solvate thereof, has an advantage of maintaining a balance between generation and decomposition of collagen fibers that occupy most of the extracellular matrix of the skin, and particularly promoting synthesis of collagen fibers by promoting synthesis of collagen precursors.

Description

Composition for promoting collagen synthesis comprising albiflorin as an effective ingredient}

Disclosed herein is a composition for promoting collagen synthesis.

Collagen is a major matrix monovalence produced by fibroblasts in the skin. It exists in the extracellular epilepsy, and is an important protein that accounts for 30% of the total weight of biological proteins, and has a solid triple helix structure. The main functions are known as mechanical firmness of the skin, resistance of connective tissue and tissue, and adhesion of cells, support of cell adhesion, induction of cell division and differentiation (when growth or healing of wounds). It is known that such collagen is reduced by aging and photoaging by ultraviolet irradiation. In general, the skin thickness is reduced by 65% compared to the age of 20 at 80, and this phenomenon is known to be closely related to the formation of wrinkles on the skin. . Of collagen, type I procollagen, which consists of two alpha chains and one other alpha chain, is a major component of bone, skin, and tendons.

Accordingly, the present inventors were exploring a method capable of promoting the synthesis of collagen, and confirmed that albiflorin is effective in promoting collagen synthesis according to the synthesis of collagen precursor, and completed the present invention.

KR Registered Patent Publication No. 10-1702389 KR Publication No. 10-2012-0095296

In one aspect, an object of the present invention is to provide a composition for promoting collagen synthesis.

In order to achieve the above object, in one aspect the present invention provides a composition for promoting collagen synthesis comprising albiflorine, a salt thereof, an isomer, a hydrate or a solvate as an active ingredient.

In one aspect, the active ingredient of the present invention, albiflorine, salts, isomers, hydrates or solvates thereof, can maintain the balance of production and degradation of collagen fibers that occupy most of the extracellular matrix of the skin, and in particular according to the synthesis of collagen precursors. It has the advantage that it can promote the synthesis of collagen.

1 is a view showing the results confirming the effect of promoting the synthesis of collagen precursor.
2 is a view showing the results confirming the proliferation effect of fibroblasts producing collagen.
3 is a view showing the results of confirming the change in MMP-1 expression.

In one aspect, the present invention provides a composition for promoting synthesis of collagen comprising albiflorine, a salt, isomer, hydrate or solvate thereof as an active ingredient.

It will be described in detail below.

In the present specification,'albiflorin (albiflorin)' is a substance having a molecular weight of 480 of molecular formula C ₂₃ H ₂₈ O ₁₁ and is represented by the following Chemical Formula 1. The density is 1.6±0.1 g/cm ³ .

In the present specification,'salt' is a concentration having a relatively non-toxic and harmless effect on an individual, and any side effects resulting from the salt of albiflorin do not degrade any beneficial organic or inorganic addition salts. It includes all salts of acidic or basic groups which may be present in the compound represented by albiflorin. Examples include acid addition salts formed by free acids or metal salts formed by bases.

For example, inorganic acids and organic acids may be used as the free acid, hydrochloric acid, hydrobromic acid, bromic acid, sulfuric acid, hydrochloric acid, sulfuric acid, sulfurous acid, nitric acid or phosphoric acid may be used as the inorganic acid, acetic acid, propionic acid, etc. Hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl) benzoic acid, cinnamic acid, mandelic acid , Methanesulfonic acid, ethanesulfonic acid, 2-ethane-disulfonic acid 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-tuluenesulfonic acid, camphorsulfonic acid , 4-methylbicyclo[2,2,2]-oct-2-ene-1-carboxylic acid, glucohamtonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert-7butylacetic acid, lauryl sulfate, Gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, humaic acid or citric acid can be used. As an example, the metal salt is an alkali metal salt or an alkaline earth metal salt.

As used herein,'isomer' refers to optical isomers, ie, essentially pure enantiomers, essentially pure diastereomers or mixtures thereof, as well as one or more chemical bonds thereof. The concept includes conformational isomers and positional isomers that differ only in angles, and the positional isomers include geometric isomers such as tautomers or cis-trans isomers. do. The'essentially pure', for example, when used in connection with an enantiomer or a partial isomer, a specific compound that can exemplify an enantiomer or a partial isomer is about 90% or more, 91% or more, 92% or more, 93 % Or more, 94% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more, or 99.5% or more (w/w).

In the present specification,'hydrate' refers to a compound to which water is attached, and is a broad concept including an inclusion compound having no chemical bonding force between water and the compound.

In the present specification, the term'solvate' means a higher-order compound formed between molecules or ions of a solute and molecules or ions of a solvent.

In one aspect, the albiflorine of the present invention, salts, isomers, hydrates or solvates thereof can be used by purchasing a commercially available material, or by synthesizing them or the like.

In this specification,'dose' means to provide the composition of the present invention to a subject in any suitable way. Any mode of administration can be envisaged, for example, can be administered orally or transdermally, and the administration can include providing a functional cosmetic product in a broad sense. In one aspect, the dosage of albiflorine, salt, isomer, hydrate or solvate thereof is 0.001 or more, 0.002 or more, 0.003 or more, 0.004 or more, 0.005 or more, 0.006 or more, 0.007 or more, 0.008 or more, 0.009 or more, 0.01 or more , 0.02 or more, 0.03 or more, 0.04 or more, 0.05 or more, 0.06 or more, 0.07 or more, 0.08 or more, 0.09 or more, 0.1 or more, 0.2 or more, 0.3 or more, 0.4 or more, 0.5 or more, 0.6 or more, 0.7 or more, 0.8 or less, 0.9 Or less, 1 or less, 1.1 or less, 1.2 or less, 1.3 or less, 1.4 or less, 1.5 or less, 1.6 or less, 1.7 or less, 1.8 or less, 1.9 or less, 2 or less, 2.1 or less, 2.2 or less, 2.3 or less, 2.4 or less, 2.5 or less, 2.6 or less, 2.7 or less, 2.8 or less, 2.9 or less, 3 or less, 4 or less, 5 or less, 6 or less, 7 or less, 8 or less, 9 or less, 10 or less, 11 or less, 12 or less, 13 or less, 14 or less, 15 or less , 16 or less, 17 or less, 18 or less, 19 or less, 20 or less, 25 or less, 30 or less, 35 or less, 40 or less, 45 or less, 50 or less, 55 or less, 60 or less, 65 or less, 70 or less, 75 or less, 80 Hereinafter, it may be 85 or less, 90 or less, 95 or less, 100 or less mg/kg/day, but is not limited thereto, and may vary according to various factors such as age, skin condition, health condition, and complications of the subject to be administered.

In one aspect, albiflorine, a salt, isomer, hydrate or solvate thereof is 0.000001 or more, 0.000005 or more, 0.00001 or more, 0.00005 or more, 0.0001 or more, 0.0005 or more, 0.001 or more, 0.005 or more, 0.01 or more, based on the total weight of the composition 0.03 or more, 0.05 or more, 0.08 or more, 0.1 or more, 0.3 or more, 0.5 or more, 0.8 or more, 1 or more, 1.3 or more, 1.5 or more, 1.8 or more, 2 or more, 2.3 or more, 2.5 or more, 2.8 or more, 3 or more, 3.3 or more , 3.5 or more, 3.8 or more, 4 or more, 4.3 or more, 4.5 or more, 4.8 or more, 5 or less, 5.3 or less, 5.5 or less, 5.8 or less, 6 or less, 6.3 or less, 6.5 or less, 6.7 or less, 7 or less, 7.3 or less, 7.5 Or less, 7.8 or less, 8 or less, 8.3 or less, 8.5 or less, 8.8 or less, 9 or less, 9.3 or less, 9.5 or less, 9.8 or less, but may be included in 10% by weight, but is not limited thereto.

In one aspect,'collagen' is a fibrous protein that is shaped like a rope twisted by triplets of three molecules. For example, the collagen may be collagen in the skin, and more preferably, collagen in the skin extracellular matrix.

In one aspect, the composition may promote the synthesis of a collagen precursor, for example, the collagen precursor may be type I procollagen.

In one aspect, promoting collagen synthesis may mean promoting collagen precursor synthesis.

In one aspect, promoting collagen synthesis may mean promoting fibroblast proliferation to produce collagen.

In one aspect, the composition may be to promote skin elasticity.

In one aspect, the composition may be to improve skin wrinkles.

In one aspect, the composition may have a purpose of preventing or improving aging according to promoting collagen synthesis. The aging may be endogenous or exogenous aging.

In the present specification,'prevention' may mean all actions that inhibit the occurrence of a preventive object or delay the occurrence of a preventive object by administration of a composition.

In the present specification,'improvement' is to improve the condition of the subject to be prevented by administration of the composition. For example, the improvement used in the present invention reduces the number of wrinkles due to aging or makes the skin surface more elastic. It can mean anything you do to make your skin look younger.

In one aspect, the composition may be for MMP-1 inhibition.

In one aspect, the composition of the present invention may be a cosmetic composition.

In the present specification, the'cosmetic composition' is a concept including all things that make the appearance of the human body beautiful, and the cosmetic composition for improving skin elasticity or improving skin wrinkles of the present invention is a physiological phenomenon according to the biorhythm and adversely affects the skin. The concept refers to an object that suppresses the appearance of the human body to be beautiful, but is not limited thereto.

In one aspect, the cosmetic composition is a conventional auxiliaries and carriers, such as antioxidants, stabilizers, solubilizers, vitamins, pigments, fragrances, etc., commonly used in cosmetic compositions in addition to albiflorine, salts, isomers, hydrates or solvates thereof. It may be further included. For example, the cosmetic composition may further include auxiliary components such as glycerin, butylene glycol, polyoxyethylene cured castor oil, tocopheryl acetate, citric acid, panthenol, squalane, sodium citrate, allantoin, and the like. .

In one aspect, since the cosmetic composition is basically applied to the skin, it can be prepared in any formulation that is conventionally prepared with reference to cosmetic compositions in the art. As an example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations and sprays, etc. It is not limited. More specifically, it can be prepared in the form of a flexible lotion, nutrition lotion, nutrition cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, mask pack, spray or powder.

In one aspect, when the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc as carrier components, Zinc oxide, and the like.

In one aspect, when the formulation of the present invention is a powder or a spray, as a carrier component, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, etc. may be included, and particularly in the case of a spray, additional chloro And propellants such as fluorohydrocarbon, propane/butane, and dimethyl ether.

In one aspect, when the formulation of the present invention is a solution or emulsion, a carrier component may include a solvent, a solubilizing agent, an emulsifying agent, etc., specifically water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol , Benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, fatty acid ester of sorbitan, and the like.

In one aspect, when the formulation of the present invention is a suspension, a liquid diluent such as water, ethanol, propylene glycol as a carrier component; Suspension agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester; Microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, trakant, and the like.

In one aspect, when the formulation of the present invention is a surfactant-containing cleansing, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, as a carrier component Sarcosinates, fatty acid amide ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, ethoxylated glycerol fatty acid esters, and the like.

In one aspect, the composition of the present invention may be a dietary supplement composition.

In this specification, the'health functional food composition' is a food group or food composition that provides added value to act and express the function of the food for a specific purpose by using physical, biochemical, or biotechnological techniques on the food, or a biodefense rhythm of the food composition. It is a processed food designed to sufficiently express the body's regulation functions for regulation, disease prevention and recovery, etc., and should be harmless to the human body when taken for a long time.

In one aspect, the dietary supplement may include a food-acceptable food supplement additive, and may further include suitable carriers, excipients, and diluents commonly used in the manufacture of dietary supplements.

In one aspect, the dietary supplement composition may be used as a food additive, in which case the composition may be added as such or used with other food or food ingredients according to conventional methods. The mixing amount of the active ingredient can be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment).

In one aspect, examples of types of health functional foods include dairy products including ice cream, various soups, beverages, teas, drinks, alcoholic beverages, and vitamin complexes, and the function of the food in a general sense to a specific purpose. It includes all foods that are designed to fully express to the living body the functions of controlling the body, such as control of the biological defense rhythm, disease prevention and recovery of the food group or food composition that has added value to action and expression.

In one aspect, the dietary supplement composition is a variety of nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives , Glycerin, alcohol, carbonic acid used in carbonated beverages, and the like.

Duplicate contents are omitted in consideration of the complexity of the present specification, and terms that are not otherwise defined herein have meanings commonly used in the technical field to which the present invention pertains. Also, as used herein,'or' is a concept including'and' unless expressly stated to the contrary.

Hereinafter, examples and manufacturing examples will be described in detail to help understanding of the present invention. However, the following examples and manufacturing examples are only illustrative of the contents of the present invention, and the scope of the present invention is not limited to the following examples and manufacturing examples. Examples and manufacturing examples of the present invention are provided to more fully describe the present invention to those skilled in the art.

Example 1. Confirmation of the effect of promoting collagen precursor biosynthesis by albiflorin

In order to confirm the collagen fiber regeneration effect, a change in the content of collagen precursor type I procollagen was confirmed. Specifically, the fibroblasts obtained from ATCC were dispensed into a medium containing 10% (v/v) FBS, and then cultured for 24 hours at 37°C and 5% CO ₂ conditions. Then, independently treated with 0.2 μg/ml, 1 μg/ml, or 5 μg/ml of Albiflorin (Chem Faces), and cultured for 72 hours. After 72 hours, only the culture medium was partially separated, and PIP ELISA (Takara) was performed in a manner commonly used in the art. On the other hand, albiflorin or TGF-β was not treated as a negative control, and 5 ng/ml of transforming growth factor beta (TGF-β) was added to the positive control instead of albiflorin.

Subsequently, the culture medium was separated and the remaining cells were pulverized to extract type I procollagen protein, and the total amount of protein was measured by performing BCA (Bicinchoninic acid) analysis in a manner commonly used in the art. The result obtained by performing the PIP ELISA was corrected. The results are shown in FIG. 1.

As shown in FIG. 1, it was confirmed that the rate of promoting the production of type I procollagen by albiflorin was about 32-44%. This indicates that albiflorin has excellent procollagen precursor biosynthesis promotion and thus collagen synthesis promotion effect.

Example 2. Confirmation of the effect of promoting proliferation of fibroblasts by albiflorin

In order to confirm the collagen fiber regeneration effect, changes in cell proliferation of fibroblasts synthesizing collagen were confirmed. Specifically, the fibroblasts obtained from ATCC were dispensed into a medium containing 10% (v/v) of FBS, and then cultured for 24 hours under 37°C and 5% CO ₂ conditions. Then, Albiflorin (Chem Faces) was treated independently with 5 μg/ml, 10 μg/ml, or 20 μg/ml, and then cultured for 72 hours. After 72 hours, a cell count kit-8 (CCK8) analysis was performed in a manner commonly used in the art to measure cell viability, that is, cell proliferation rate. The results are shown in FIG. 2.

As shown in Fig. 2, it was confirmed that the proliferation rate of fibroblasts by albiflorin was about 7-14%. This indicates that Albiflorin has an excellent fibroblast proliferation promoting effect and thus a collagen synthesis promoting effect.

Example 3. Confirmation of the inhibitory effect of MMP-1 by Albiflorin

In order to confirm the effect of reducing the degradation of collagen fibers, changes in MMP-1 expression were confirmed. Specifically, the fibroblasts obtained from ATCC were dispensed into a medium containing 10% (v/v) FBS, and then cultured for 24 hours at 37°C and 5% CO ₂ conditions. Then, independently treated with 0.2 μg/ml, 1 μg/ml, or 5 μg/ml of Albiflorin (Chem Faces), and cultured for 24 hours. After 24 hours, the cells were collected and RNA was extracted using a method commonly used in the art, and real-time RT-PCR was performed using human MMP-1 primer (MMP1 Hs00899658_m1, Life technology). . On the other hand, albiflorin or TGF-β was not treated as a negative control, and 5 ng/ml of TGF-β was added to the positive control instead of albiflorin. As a control gene (Enogenous Control), human RPLP0 (Large Ribosomal Protein) was used to obtain the total expression of the MMP-1 gene. The results are shown in FIG. 3.

As shown in Fig. 3, it was confirmed that the inhibition rate of MMP-1 expression by albiflorine was about 38-50%. This indicates that Albiflorin has excellent MMP-1 expression inhibition and thus a synthetic collagen maintenance effect.

Formulation Example 1. Preparation of cosmetic preparation

1-1. Flexible cosmetic production

Albiflorin 0.1 wt%, 1,3-butylene glycol 5.2 wt%, oleyl alcohol 1.5 wt%, ethanol 3.2 wt%, polysorbate 20 3.2 wt%, benzophenone-9 2.0 wt%, carboxyl vinyl polymer 1.0 By weight%, glycerin 3.5% by weight, a small amount of fragrance, a small amount of preservatives and the remaining amount of purified water were mixed to prepare softened cosmetic water in a conventional manner.

1-2. Milk lotion manufacturing

Albiflorin 0.1% by weight, glycerine 5.1% by weight, propylene glycol 4.2% by weight, tocopheryl acetate 3.0% by weight, liquid paraffin 4.6% by weight, triethanolamine 1.0% by weight, squalane 3.1% by weight, macadamia nut oil 2.5% by weight, polysol Bait 60 1.6% by weight, sorbitan sesquirolate 1.6% by weight, propylparaben 0.6% by weight, carboxyvinyl polymer 1.5% by weight, trace amount of fragrance, trace amount of preservative, and residual amount of purified water to mix the milk lotion It was prepared.

1-3. Nutrition cream manufacturing

Albiflorin 0.5 wt%, Glycerin 4.0 wt%, Vaseline 3.5 wt%, Triethanolamine 2.1 wt%, Liquid Paraffin 5.3 wt%, Squalane 3.0 wt%, Beeswax 2.6 wt%, Tocopheryl Acetate 5.4 wt%, Polysorbate 60 3.2 A nutritional cream was prepared in a conventional manner by mixing weight percent, carboxyl vinyl polymer 1.0 weight percent, sorbitan sesquioleate 3.1 weight percent, trace amounts of fragrance, trace amounts of preservatives and residual amount of purified water.

Formulation Example 2. Preparation of food preparation

2-1. Health food manufacturing

Albiflorin 100mg, vitamin mixture proper amount, vitamin A acetate 70g, vitamin E 1.0mg, vitamin B1 0.13mg, vitamin B2 0.15mg, vitamin B6 0.5mg, vitamin B12 0.2g, vitamin C 10mg, biotin 10g, nicotinamide 1.7 ㎎, folic acid 50g, calcium pantothenate 0.5mg, mineral mixture amount, ferrous sulfate 1.75mg, zinc oxide 0.82mg, magnesium carbonate 25.3mg, potassium phosphate 15mg, dicalcium phosphate 55mg, potassium citrate 90mg, After mixing 100 mg of calcium carbonate and 24.8 mg of magnesium chloride, granules were prepared and healthy foods were prepared according to a conventional method.

2-2. Health drink manufacturing

Albiflorin 100mg, vitamin C 15g, vitamin E (powder) 100g, iron lactate 19.75g, zinc oxide 3.5g, nicotinic acid amide 3.5g, vitamin A 0.2g, vitamin B1 0.25g, vitamin according to normal health drink manufacturing method After mixing 0.3 g of B2 and a fixed amount of water and stirring and heating at 85° C. for about 1 hour, the resulting solution was filtered, obtained in a sterilized 2 L container, sealed and sterilized, and then refrigerated to prepare a health drink.

Claims (10)

Albiflorin (albiflorin), a salt, isomer, hydrate or solvate composition for promoting collagen synthesis comprising as an active ingredient. According to claim 1,
A composition in which the dosage of albiflorine, salt, isomer, hydrate or solvate thereof is 0.001 to 100 mg/kg/day. According to claim 1,
Albiflorin, its salt, isomer, hydrate or solvate composition comprising 0.000001 to 10% by weight based on the total weight of the composition. According to claim 1,
The collagen is a composition that is collagen in the skin. According to claim 1,
The composition is a composition that promotes the synthesis of collagen precursor. According to claim 1,
The composition is a composition that promotes fibroblast proliferation. According to claim 1,
The composition is a composition that promotes skin elasticity. According to claim 1,
The composition is a composition for improving skin wrinkles. According to claim 1,
The composition is a cosmetic composition. According to claim 1,
The composition is a health functional food composition.

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