KR20210074770A - Composition for inducing alteration of surrounding environment of a aged cell - Google Patents

Abstract

Provided are a composition for promoting the induction of environmental changes around aging skin cells, comprising a compound represented by the chemical formula 1, a derivative thereof, or a cosmetically acceptable salt thereof as an active ingredient. In the chemical formula 1, each substituent is the same as defined in the specification.

Description

A composition for promoting induction of environmental changes around aging skin cells {COMPOSITION FOR INDUCING ALTERATION OF SURROUNDING ENVIRONMENT OF A AGED CELL}

The present disclosure relates to a composition that promotes the growth of only human-derived young skin cells.

The skin, the largest organ of the human body, has a function to protect the body from external physical and chemical stimuli and to maintain homeostasis such as humidity and body temperature. However, as the person ages or is continuously exposed to external stimuli, the skin is damaged and the physiological function is deteriorated, and the skin aging proceeds rapidly. Such skin aging is a natural phenomenon that inevitably occurs with aging, or the demand for quality of life is increasing due to the improvement of living standards. measures are urgently required.

Skin aging is affected by various factors such as genetics and environmental factors, and it is largely divided into natural aging or intrinsic aging and extrinsic aging. Natural aging or intrinsic aging is an aging phenomenon that occurs over time according to genetic information, and is mainly observed in skin that is not exposed to sunlight, and is characterized by fine wrinkles and reduced skin elasticity, and artificially difficult to control. Extrinsic aging is an aging phenomenon caused by external environmental factors, especially UV rays present in sunlight. Also called photoaging, it appears in areas exposed to a lot of sunlight, deep wrinkles, rough skin texture, and pigmentation. , skin tone and skin elasticity are reduced, and artificial adjustment is easy. Therefore, research to prevent extrinsic aging has been continued, and in particular, research on the prevention of wrinkle formation due to exogenous photoaging that is progressed by long-term UV exposure is attracting attention (Gilchre st BA, J. Am. Acad. Dermatol., 1989). :21:610-613).

Therefore, the term aging used in cosmetic compositions up to now means all extrinsic aging, especially skin aging caused by extrinsic photoaging, and anti-aging refers to a process in which cells aged by external environmental factors are removed (suppressed aging) or rejuvenated. It was meant to show a recovery phenomenon (cell rejuvenation). And this concept of anti-aging was based on what was secured through the improvement of aging factors of individual cells. However, it is true that it did not achieve the desired actual effect in various applications including the clinical part. According to the recent trend of the Dermatological Society, research that pursues changes in the overall environment rather than inhibition of aging or cell rejuvenation through the anti-aging mechanism of individual cells is trending. mentioned as important.

Therefore, the present inventors are not limited by the definition of aging used in conventional cosmetic compositions, and can be applied to a wide range of aging (endogenous aging and exogenous aging), and instead of inhibiting aging or cell rejuvenation, cells that are already aged in an aged environment are intact It led to the development of a composition capable of changing an aged environment into a non-aging environment by promoting only the growth of young cells that have not yet aged.

This completely deviates from the conventional concept of anti-aging, and changing the aging environment into a non-aging environment by specifically increasing the number of young cells around while leaving the senescent cells as they are is the existing anti-aging mechanism ( It is expected to have a mechanism completely different from the mechanism of aging inhibition or cell rejuvenation).

One embodiment is a mechanism of relatively significantly increasing the number of young cells than the number of senescent cells by specifically promoting the growth of only young cells that have not yet aged while maintaining the number of senescent cells in an already aged environment Through this, it is intended to provide a composition that can change the aging environment.

According to one embodiment, human skin containing a compound represented by the following Chemical Formula 1, a derivative thereof, or a cosmetically acceptable salt thereof as an active ingredient, and not stained with SA-β-gal (senescence associated-beta galactosidase) To provide a composition for promoting changes in the environment around aging skin cells, which promotes only the growth of cells.

[Formula 1]

In Formula 1,

R ¹ and R ² are each independently a hydroxyl group or a carboxyl group,

n is an integer from 1 to 3.

The compound represented by Formula 1 may be represented by Formula 1-1 below.

[Formula 1-1]

In Formula 1-1,

R ¹ is a hydroxyl group,

R ² is a carboxyl group.

The compound represented by Formula 1 may be included in an amount of 0.01 wt% to 5 wt% based on the total amount of the composition.

The skin cells may be pigment-forming cells.

The skin cells may be fibroblasts.

The composition increases the number of human-derived young skin cells that are not stained with SA-β-gal (senescence associated-beta galactosidase), and human-derived senescent cells that are stained with SA-β-gal (senescence associated-beta galactosidase). The number of cells can be maintained as it is.

The composition may be a cosmetic composition.

The composition according to an embodiment of the present invention specifically grows only the number of young cells while maintaining the number of senescent cells and non-aging young cells constituting the aged skin, thereby removing the aged cells or aging. It can improve the aging skin environment without returning old cells to young cells.

1 is an optical micrograph showing the morphology and cell number of pigment-forming cells before and after UVB treatment.
2 is an optical micrograph of observation of changes in the morphology and number of UVB-treated pigment-forming cells according to an increase in the concentration of the compound represented by Formula E. FIG.
3 is a graph showing the ratio of the total number of pigment-forming cells, the number of senescent pigment-forming cells, and the number of senescent pigment-forming cells to the total number of pigment-forming cells, for each concentration of the compound represented by Formula E.
4 is an optical micrograph showing the morphology and cell number of fibroblasts before and after UVB treatment.
5 is an optical micrograph of observation of changes in the morphology and cell number of UVB-treated fibroblasts according to an increase in the concentration of the compound represented by Formula E. FIG.
6 is a graph showing the ratio of the number of senescent fibroblasts to the total number of fibroblasts, the number of senescent fibroblasts, and the total number of fibroblasts for each concentration of the compound represented by Formula E.

Hereinafter, embodiments of the present invention will be described in detail so that those of ordinary skill in the art to which the present invention pertains can easily implement them. However, the present invention may be embodied in many different forms and is not limited to the embodiments described herein.

As used herein, senescent cells refer to cells that are stained with SA-β-gal (senescence associated-beta galactosidase), and young cells refer to cells that are not stained with SA-β-gal (senescence associated-beta galactosidase). do.

In the present specification, when a part such as a layer, film, region, plate, etc. is "on" another part, it includes not only the case where the other part is "directly on" but also the case where there is another part in the middle. Conversely, when we say that a part is "just above" another part, we mean that there is no other part in the middle.

Unless otherwise defined herein, "combination" means mixing or copolymerization. In addition, "copolymerization" means block copolymerization or random copolymerization, and "copolymer" means block copolymerization or random copolymerization.

Hereinafter, a composition for promoting growth of young skin cells derived from the human body that is not stained with SA-β-gal (senescence associated-beta galactosidase) according to an embodiment will be described.

A composition for promoting environmental change around aging skin cells that promotes only the growth of human-derived skin cells that are not stained with SA-β-gal (senescence associated-beta galactosidase) according to an embodiment includes a compound represented by the following Chemical Formula 1, A derivative or a cosmetically acceptable salt thereof is included as an active ingredient.

[Formula 1]

In Formula 1,

R ¹ and R ² are each independently a hydroxyl group or a carboxyl group,

n is an integer from 1 to 3.

For example, the compound represented by Formula 1 may be represented by Formula 1-1 below.

[Formula 1-1]

In Formula 1-1,

R ¹ is a hydroxyl group,

R ² is a carboxyl group.

The present application is an invention that focuses on changes in the environment, unlike existing anti-aging technologies that focus on inhibiting aging of individual cells or improving individual aging factors. Although the recovery phenomenon in which senescent cells are removed or rejuvenated by UV is not shown herein, the growth of young cells (cells in which the aging factor is not revealed) among senescent cells is a compound represented by Formula 1, its A composition containing a derivative or a cosmetically acceptable salt thereof as an active ingredient has a concentration-dependent increase characteristic, replacing the aging phenomenon with a completely different mechanism of existing anti-aging.

The compound represented by Formula 1 selectively promotes growth of only unsenescent young pigment-forming cells between senescent human-derived primary melanocytes (MC) and non-senescent human-derived primary melanocytes. can

The compound represented by Formula 1 can selectively promote growth of only unsenescent young fibroblasts between aged human-derived fibroblasts (FB) and non-senescent human-derived fibroblasts (primary fibroblasts).

That is, the skin cells may be pigment-forming cells or fibroblasts.

In the composition, the compound represented by Formula 1, a derivative thereof, or a cosmetically acceptable salt thereof may be included in a content range of 0.01 wt% to 5 wt% based on the total amount of the composition. When the compound represented by Formula 1, a derivative thereof, or a cosmetically acceptable salt thereof is used in an amount of less than 0.01% by weight, the content is too low among senescent cells (cells in which the aging factor is not exposed) The effect of accelerating the growth of cells is very insignificant, and when used in an amount of more than 5 wt%, even a content of 5 wt% or less has the effect of promoting the growth of already young cells (cells in which the aging factor is not revealed). It can be uneconomical.

That is, since the composition according to one embodiment contains the compound represented by Formula 1, a derivative thereof, or a cosmetically acceptable salt thereof as an active ingredient, SA-β-gal (senescence associated-beta galactosidase) staining is not performed. It is possible to increase the number of human-derived young skin cells only, and to maintain the number of human-derived senescent cells that are stained with SA-β-gal (senescence associated-beta galactosidase).

As used herein, the term "cosmetically effective amount" refers to an amount sufficient to exhibit the desired physiological or cosmetic activity when the physiologically active ingredient is administered to an animal or human. However, the cosmetically effective amount may be appropriately changed depending on the severity of symptoms, the age, weight, health status, sex, administration route and period of use of the patient.

In addition, as used herein, "cosmetically acceptable" means that it is physiologically acceptable and does not normally cause allergic reactions such as skin troubles or dizziness or similar reactions when administered to humans.

Meanwhile, the composition may further include a carrier, excipient, diluent, and the like, and examples thereof include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In addition, fillers, anti-agglomeration agents, lubricants, wetting agents, fragrances, emulsifiers and preservatives may be further included.

For example, the composition may be a cosmetic composition.

In the present specification, "cosmetics" may refer to all substances that may have additional medical functions in addition to cosmetic functions as well as cosmetic functions.

The formulation of the cosmetic composition is not particularly limited, and may be appropriately selected according to the purpose.

For example, the cosmetic composition is formulated as a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray. may be, but is not limited thereto. More specifically, cosmetic compositions such as detergents, tonics, hair dressings, nutrient lotions, essences, serums, treatments, conditioners, shampoos, lotions, hair or hair dyes, oil-in-water (O/W) type, water-in-oil (O/W) It can be formulated as a basic cosmetic such as W) type. For example, the composition may include skin lotion, skin toner, astringent, lotion, milk lotion, moisture lotion, nourishing lotion, massage cream, nourishing cream, moisture cream, hand cream, ointment, foundation, essence, nourishing essence, pack, soap, cleansing It may have one formulation selected from the group consisting of foam, cleansing lotion, cleansing cream, body lotion, body cleanser, lotion, ointment, gel, cream, patch and spray. In addition, the composition, in each formulation, other components other than the above-mentioned essential components can be appropriately selected and formulated by those skilled in the art without difficulty depending on the type or purpose of use of other external preparations. For example, it may further include a sunscreen, a hair conditioning agent, a fragrance, and the like.

The cosmetic composition may contain a cosmetically acceptable medium or base. It is in any formulation suitable for topical application, for example solutions, gels, solid or kneaded dry products, emulsions obtained by dispersing the oily phase in an aqueous phase, suspensions, microemulsions, microcapsules, microgranules or ionic (liposomes) and/or It may be provided in the form of a non-ionic vesicular dispersant, or in the form of a cream, skin, lotion, powder, ointment, spray or concealer stick. These compositions can be prepared according to conventional methods in the art.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizer or emulsifier is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butylglycol oil, glycerol fatty esters, fatty acid esters of polyethylene glycol or sorbitan.

When the formulation of the present invention is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystals Adult cellulose, aluminum metahydroxide, bentonite, agar or tracanth may be used.

When the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component. can

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and in particular, in the case of a spray, additional chlorofluorohydrocarbon, propane /may contain propellants such as butane or dimethyl ether.

In one embodiment of the present invention, the cosmetic composition may additionally contain a thickener. The thickener included in the cosmetic composition of the present invention is methyl cellulose, carboxy methyl cellulose, carboxy methyl hydroxy guanine, hydroxy methyl cellulose, hydroxyethyl cellulose, carboxy vinyl polymer, polyquaternium, cetearyl alcohol, stearic acid, Carrageenan and the like may be used, and preferably, at least one of carboxymethyl cellulose, carboxyvinyl polymer, and polyquaternium may be used, and most preferably, carboxyvinyl polymer may be used.

In one embodiment of the present invention, the cosmetic composition may contain various suitable bases and additives as necessary, and the types and amounts of these components can be easily selected by the inventor. It may contain acceptable additives as necessary, for example, may further include components such as preservatives, pigments, and additives conventional in the art.

Specifically, the preservative may be phenoxyethanol or 1,2-hexanediol, and the fragrance may be an artificial fragrance.

And, in one embodiment of the present invention, the cosmetic composition may include a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingolipids, and seaweed extract. Other ingredients that may be added include oils and fats, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, disinfectants, antioxidants, plant extracts, pH adjusters, alcohols, colorants, fragrances, A blood circulation promoter, a cooling agent, an anti-inflammatory agent, purified water, etc. are mentioned.

In addition, the compounding component which may be added other than this is not limited to this, Moreover, any said component can be mix|blended within the range which does not impair the objective and effect of this invention.

When the cosmetic composition is formulated as a cosmetic, it may contain known dermatologically acceptable excipients that act as carriers for active ingredients, and specifically, International cosmetic ingredient dictionary, 6th ed., The cosmetic, Toiletry and Fragrance Association, Inc., Washington, 1995 may be referred to. These documents are incorporated as part of this specification.

Furthermore, the cosmetic composition according to an embodiment may be used as a pharmaceutical composition or as a health functional food. For example, it can be easily utilized as a main raw material of food, an auxiliary raw material, a food additive, a functional food or a beverage.

The "food" means a natural product or processed product containing one or more nutrients, and preferably means a state that can be eaten directly through some processing process, and in a conventional sense, food , which includes all food additives, functional foods and beverages.

Foods to which the composition for food can be added include, for example, various foods, beverages, gum, tea, vitamin complexes, functional foods, and the like. In addition, special nutritional foods (eg, formula milk, young, baby food, etc.), processed meat products, fish meat products, tofu, jelly, noodles (eg, ramen, noodles, etc.), breads, health supplements, seasoned foods (eg, soy sauce) , soybean paste, red pepper paste, mixed paste, etc.), sauces, confectionery (eg snacks), candy, chocolate, gum, ice cream, dairy products (eg fermented milk, cheese, etc.), other processed foods, kimchi, pickled foods (various kimchi) , pickles, etc.), beverages (eg, fruit beverages, vegetable beverages, soy milk, fermented beverages, etc.), and natural seasonings (eg, ramen soup, etc.), but are not limited thereto. The food, beverage or food additive may be prepared by a conventional manufacturing method.

In addition, the term "functional food" or "health functional food" refers to a food group or food composition in which added values are added to the food to act and express the function of the food for a specific purpose using physical, biochemical, or bioengineering methods, etc. It refers to food that is designed and processed to sufficiently express the body control functions related to defense rhythm control, disease prevention and recovery, etc. to the living body. Specifically, it may be a health functional food. The functional food may include a food supplementary additive that is pharmaceutically acceptable, and may further include an appropriate carrier, excipient and diluent commonly used in the manufacture of functional food.

The type of the dietary supplement is not limited thereto, but may be in the form of powder, granule, tablet, capsule or beverage.

Advantages and features of the present invention, and methods for achieving them, will become apparent with reference to the embodiments described below in detail. Hereinafter, the present invention will be described in detail by way of Examples. However, these examples are for describing the present invention in detail, and the scope of the present invention is not limited to these examples.

(Example)

Test Example 1: Changes in pigment-forming cell morphology and cell number by UVB treatment

UVB was induced to the pigment-forming cells to age the pigment-forming cells, and as a result, the appearance of the cells was changed morphologically. . Thereafter, a compound represented by the following Chemical Formula E (Sigma-Aldrich) was treated. As a result, it was confirmed that the number of cells increased again in a concentration-dependent manner of the compound represented by Formula E (see FIGS. 1 and 2). In addition, by measuring the total number of cells ((A) in FIG. 3) and the number of senescent cells ((B) in FIG. 3), the ratio of the number of senescent cells stained with SA-β-gal to the total number of cells (FIG. 3) (C)) was calculated, and it was confirmed that the ratio of the number of aged cells to the total number of cells decreased in a concentration-dependent manner of the compound represented by Formula E (see FIG. 3).

[Formula E]

Test Example 2: Change in the number of fibroblast cells after UVB treatment

UVB was induced to fibroblasts to age the fibroblasts, and as a result, the morphological appearance of the cells was changed, and it was confirmed that about 60% of the cells were killed due to apoptosis of the cells due to abrupt aging. Thereafter, the compound represented by Formula E was treated. As a result, it was confirmed that the number of cells increased again in a concentration-dependent manner of the compound represented by Formula E (see FIGS. 4 and 5). In addition, by measuring the total number of cells ((A) in Fig. 6) and the number of senescent cells stained with SA-β-gal ((B) in Fig. 6), the ratio of the number of senescent cells to the total number of cells (Fig. 6) (C)) was calculated, and it was confirmed that the ratio of the number of aged cells to the total number of cells decreased in a concentration-dependent manner of the compound represented by Formula E (see FIG. 6 ).

Although preferred embodiments of the present invention have been described in detail above, the scope of the present invention is not limited thereto, and various modifications and improvements by those skilled in the art using the basic concept of the present invention defined in the following claims are also present. It belongs to the scope of the invention.

Claims (7)

A compound represented by the following formula (1), a derivative thereof, or a cosmetically acceptable salt thereof, as an active ingredient,
It promotes only the growth of human-derived skin cells that cannot be stained with SA-β-gal (senescence associated-beta galactosidase).
A composition for promoting induction of environmental changes around aging skin cells:
[Formula 1]

In Formula 1,
R ¹ and R ² are each independently a hydroxyl group or a carboxyl group,
n is an integer from 1 to 3. In claim 1,
The compound represented by the formula (1) is represented by the following formula (1-1), a composition for promoting environmental change around aging skin cells:
[Formula 1-1]

In Formula 1-1,
R ¹ is a hydroxyl group,
R ² is a carboxyl group. In claim 1,
The compound represented by Formula 1 is included in an amount of 0.01% to 5% by weight based on the total amount of the composition, a composition for promoting environmental change around aging skin cells. In claim 1,
Wherein the skin cells are pigment-forming cells, a composition for promoting changes in the environment around aging skin cells. In claim 1,
The skin cells are fibroblasts, a composition for promoting environmental change around aging skin cells. In claim 1,
The composition is
Increases the number of cells only in young skin cells derived from the human body that cannot be stained with SA-β-gal (senescence associated-beta galactosidase);
A composition for promoting changes in the environment around aging skin cells, maintaining the number of human-derived senescent cells that are stained with SA-β-gal (senescence associated-beta galactosidase). In claim 1,
The composition is a cosmetic composition, a composition for promoting changes in the environment around aging skin cells.

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