KR20180097876A - Composition containing 1,5-isoquinolinediol for anti-aging and anti-winkle of skin - Google Patents

Abstract

The present invention relates to a cosmetic composition for preventing skin aging and wrinkles and a composition for preventing hair loss, which comprise 1,5-isoquinoline diol as an active ingredient. The composition of the present invention can prevent the skin and scalp from aging by exhibiting antioxidative effect and suppressing effect of photoaging due to ultraviolet rays of the 1,5-isoquinoline diol, thereby suppressing collagenase and alleviating wrinkles of the skin.

Description

TECHNICAL FIELD The present invention relates to a composition for preventing skin aging and improving wrinkles, which comprises 1,5-isoquinoline diol. BACKGROUND OF THE INVENTION 1. Field of the Invention [0001]

The present invention relates to a cosmetic composition for preventing skin aging and wrinkles containing 1,5-isoquinoline diol and a composition for preventing hair loss.

Skin is located at the outermost part of the body and plays the most fundamental and important role in protecting the body against various factors from the outside. To this end, the skin is composed of various layers and cells. The skin is largely divided into the epidermis and the dermis. The epidermis consists of keratinocytes, melanin-forming cells and immune cells, and functions as a skin barrier. The dermis has dermal fibroblasts, which regulate skin elasticity and wrinkles .

The dermal fibroblasts present in the dermis are the most important factors for the skin wrinkles by allowing the fibrous proteins collagen and elastin to be expressed in the elasticity and flexibility of the skin. There are 14 types of collagen in total, and type I collagen (type Ⅰ collagen) mainly exists in the skin. Collagen is produced by twining two α1 and one α2 chains into a triple helix, and these chains are expressed from the Col1A1 and Col1A2 genes. The collagen produced in the cells is secreted out of the cell and combined with each other in the extracellular matrix to form a collagen fiber. Such collagen synthesis is reduced by the external environment such as ultraviolet rays or aging of the skin, and promotes collagen degradation by increasing the activity of matrix metalloproteases, a collagenase that expresses dermal fibroblasts, And the elasticity and flexibility of the skin are reduced. As such, skin problems on the epidermis and dermis can not be solved by cosmetics such as moisturizers alone, and they can restore the function of keratinocytes and dermal fibroblasts, which play an important role in each skin area need.

Also, hair follicles and hair are maintained by repeating hair growth and hair loss around the cycle of growth, regenerator, and rest period. However, people with alopecia of hair, hair on the scalp to stop the activity of the papillae, the hair on the scalp to stay on the hair in the state of the appearance of hair loss appears. Minoxidil and pinasteride, approved by the US Food and Drug Administration (FDA), are the only hair growth agents used to overcome this problem. However, there is a report that minoxidil induces stickiness and skin irritation, and pinastaride is reported to have side effects of sexual dysfunction. Also, it is known that it is effective only when steady dose is taken, which makes it inconvenient to use.

Korean Patent Publication No. 10-2005-0019918

The inventors of the present invention have confirmed that 1,5-isoquinoline diol has an effect of preventing aging of the skin, in particular of preventing photoaging and improving skin wrinkles, thus completing the present invention.

In order to achieve the above object, the present invention provides a cosmetic composition for preventing skin aging and wrinkles comprising 1,5-isoquinoline diol or a pharmaceutically acceptable salt thereof as an active ingredient.

The present invention also provides a composition for preventing hair loss comprising 1,5-isoquinoline diol or a pharmaceutically acceptable salt thereof as an active ingredient.

The present invention firstly proves the use of 1,5-isoquinoline diol to prevent skin aging and improve wrinkles. It suppresses active oxygen species generated by ultraviolet rays and suppresses photoaging, thereby effectively suppressing aging of skin or scalp have. In addition, the composition of the present invention can prevent and improve skin aging and wrinkle formation by inhibiting collagenase, elastinase and the like.

1 is a graph showing the cytotoxicity evaluation results of 1,5-isoquinoline diol.
2 is a graph showing the antioxidative effect of 1,5-isoquinoline diol.
FIG. 3 is a graph showing the results of measurement of the beta-galactosidase inhibitory activity of 1,5-isoquinoline diol.
4 is a graph showing the results of measurement of the (a) collagenase inhibitory activity and (b) elastinase inhibitory activity of 1,5-isoquinoline diol.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. In the following description, detailed description of known techniques well known to those skilled in the art may be omitted. In the following description of the present invention, a detailed description of known functions and configurations incorporated herein will be omitted when it may make the subject matter of the present invention rather unclear. Also, terminologies used herein are terms used to properly represent preferred embodiments of the present invention, which may vary depending on the user, intent of the operator, or custom in the field to which the present invention belongs.

Therefore, the definition of these terms should be based on the contents throughout this specification. Throughout the specification, when an element is referred to as "comprising ", it means that it can include other elements as well, without excluding other elements unless specifically stated otherwise.

In the present specification, the term " 1,5-isoquinoline diol " means PARP-1 (poly (ADPribose) polymerase) inhibitor and has the following structure and is known to be involved in cell protection and survival.

The present invention relates to a cosmetic composition for preventing skin aging and improving wrinkles comprising 1,5-isoquinoline diol (chlorphenesin) or a pharmaceutically acceptable salt thereof as an active ingredient.

In one embodiment of the present invention, the 1,5-isoquinoline diol is used at a concentration of 0.1 μM to 10 μM, for example, 0.1 μM to 10 μM, 0.1 μM to 5 μM, 0.1 μM to 1 μM, 0.1 μM ~ 0.5 μM, 0.5 μM to 10 μM, 1 μM to 10 μM, or 5 μM to 10 μM.

In one embodiment of the present invention, the content of the 1,5-isoquinoline diol may be controlled depending on the form of the composition, for example, 0.001 to 30% by weight, 0.01 to 30% by weight, From 0.1 to 30 wt%, from 1 to 30 wt%, from 5 to 30 wt%, from 10 to 30 wt%, from 15 to 30 wt%, from 0.001 to 20 wt%, from 0.001 to 15 wt%, from 0.001 to 10 wt% 5% by weight, and 0.001% by weight to 1% by weight.

The cosmetic composition comprising the 1,5-isoquinoline diol of the present invention is effective for effectively inhibiting the production of reactive oxygen species (ROS) that cause aging of the skin, and is effective in reducing collagenase, elastinase And the like. In particular, it suppresses the beta-galactosidase activity, which is increased in photoaging of skin caused by ultraviolet rays, and is effective for inhibiting photoaging due to ultraviolet rays or the like.

The present invention also provides a composition for preventing hair loss comprising 1,5-isoquinoline diol or a pharmaceutically acceptable salt thereof as an active ingredient.

In one embodiment of the present invention, the 1,5-isoquinoline diol is used at a concentration of 0.1 μM to 10 μM, for example, 0.1 μM to 10 μM, 0.1 μM to 5 μM, 0.1 μM to 1 μM, 0.1 μM ~ 0.5 μM, 0.5 μM to 10 μM, 1 μM to 10 μM, or 5 μM to 10 μM.

In one embodiment of the present invention, the composition can be used without limitation as long as it is a general formulation of an anti-alopecia composition, and examples thereof include solutions, suspensions, pastes, gels, powders, shampoos, rinses, oils, waxes, Lt; / RTI > The amount of the 1,5-isoquinoline diol may be controlled depending on the form of the formulation. For example, the content of the 1,5-isoquinoline diol may be 0.001 to 30% by weight, 0.01 to 30% by weight, 0.1 to 30% by weight, %, 5 to 30 wt%, 10 to 30 wt%, 15 to 30 wt%, 0.001 to 20 wt%, 0.001 to 15 wt%, 0.001 to 10 wt%, 0.001 to 5 wt%, 0.001 to 1 wt% .

The composition for preventing alopecia suppresses the aging and damage of the scalp due to photoaging such as ultraviolet rays, thereby preventing hair loss.

The cosmetic composition or composition for preventing hair loss of the present invention may contain not only the above-mentioned 1,5-isoquinoline diol but also components commonly used in cosmetic compositions such as antioxidants, stabilizers, solubilizers, vitamins, pigments and Customary adjuvants such as perfumes, and carriers.

In addition to the above-mentioned 1,5-isoquinoline diol, the composition of the present invention may be used in combination with an organic UV blocking agent that has been conventionally used as long as it does not impair the skin protecting effect by reacting with 1,5-isoquinoline diol have.

Organic UV protectors include, but are not limited to, glyceryl paraben, drometrizol trisiloxane, drometrizole, dipaloyyl trioleate, disodium phenyldibenzimidazole tetrasulfonate, diethylhexylbutamidotriazone, Benzoylhexyl benzoate, di-methoxy cinnamate, a mixture of Rawson and dihydroxyacetone, methylenebis-benzotriazolyltetramethylbutylphenol, 4-methylbenzylidene camphor, menthyl anthranilate, benzophenone- Benzophenone-3 (oxybenzone), benzophenone-4, benzophenone-8 (dioxyphenylbenzene), butylmethoxydibenzoylmethane, bishexylhexyloxyphenol methoxyphenyltriazine, synoxate, Octyl-p-methoxycinnamate, polysilicon-15 (dimethicone-ethylbenzylphthalate, ethylhexylmethoxycinnamate, ethylhexylmethoxycinnamate, ethylhexylsalicylate, ethylhexyltriazone, isoamyl- Yeah At least one selected from the group consisting of terephthalylidene dicam persulfonic acid and salts thereof, tiei-salicylate and aminobenzoic acid (parabe) can be used.

In addition, the cosmetic composition of the present invention may be prepared in any form conventionally produced in the art, and examples thereof include solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactants- Containing cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray, but is not limited thereto. More specifically, the cosmetic composition of the present invention can be manufactured in the form of a soft lotion, a nutritional lotion, a nutritional cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray or a powder.

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

When the formulation of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.

In the case where the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.

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. In the case of a spray, in particular, / Propane or dimethyl ether.

When the formulation of the present invention is a surfactant-containing cleansing, the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide ether Aliphatic alcohols, fatty acid glycerides, fatty acid diethanol amides, vegetable oils, lanolin derivatives, or ethoxylated glycerol fatty acid esters can be used.

The cosmetic composition of the present invention may be used alone or in combination, or may be used in combination with other cosmetic compositions other than the present invention. In addition, the cosmetic composition according to the present invention can be used according to a conventional method of use, and may be used in a different number of times depending on the skin condition or taste of the user.

When the cosmetic composition of the present invention is a soap, a surfactant-containing cleansing formulation or a surfactant-free cleansing formulation, it may be applied to the skin and then wiped off, washed or rinsed with water. The surfactant-containing cleansing formulation may be a cleansing foam, a cleansing water, a cleansing towel and a cleansing pack. The surfactant-free cleansing formulation may be a cleansing cream, , Cleansing lotion, cleansing water and cleansing gel, but is not limited thereto.

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

[Example]

HaCaT cells and NIH3T3 cells were purchased from Korean Cell Line Bank and cultured in Dulbecco's modified Eagle medium (DMEM; Hyclone) containing 10% fetal bovine serum (FBS) and 2% penicillin / streptomycin. 1,5-isoquinoline diol (IQD, CID: 1340) was purchased from ChemBridge (CA, US), and EGCG and ursolic acid were purchased from Sigma Aldrich (US).

Example 1. Assessment of cytotoxicity

Cell viability was evaluated using MTT [3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium Bromide] assay (Promega, Ltd.). HaCaT cells and NIH3T3 cells were inoculated into 96-well plates at a concentration of 4 × 10 ³ cells per well, treated with 1,5-isoquinoline diol (24 h, 0.1 to 10 μM concentration), and the cells were treated with 5 mg / mL And incubated with MTT for 4 hours. Then, the medium was removed and 150 μL of the solubilization solution and the stop solution were added and incubated at 37 ° C. for 4 hours, and then the absorbance of the reaction solution was measured at 570 nm. Cell growth inhibition rates were normalized according to the following equation: (1-experimental group absorbance / control absorbance) x 100%.

As can be seen in Fig. 1, it was observed that in both HaCaT cells and NIH3T3 cells, there was no toxicity at a concentration of 10 μM or less for 1,5-isoquinoline diol.

Example 2. Inhibition of ROS production

(ROS) production was measured by carboxy-H2DCFDA (5- and 6-carboxy-2 ', 7'-dichlorodihydrofluorescein diacetate (Molecular Probes, Eugene, OR, USA) HaCaT cells were dispensed into 96-well plates at a density of 3 × 10 ³ , pre-treated with 1,5-isoquinoline diol (0.1, 1, 10 μM), and irradiated with UV at 60 mJ / cm ² The fluorescence intensity was then measured after 12 hours of incubation with DCFH-DA at a concentration of 10 [mu] M for 5 minutes and the fluorescence intensity was measured. The DCF fluorescence was measured using a Wallac 1420 VICTOR3 multilabel at excitation 485 nm, counter (PerkinElmer Life Sciences, Turku, Finland).

As can be seen from FIG. 2, when the UV treatment is performed, the concentration of ROS is increased by about 4 times as compared to when the UV treatment is not performed (-), but when 1,5-isoquinoline diol is treated, .

Example 3. Inhibition of beta-galactosidase activity

To evaluate the senescence-associated beta-galactosidase (SA-beta-Gal) activity during senescence, senescent cell staining kit (Sigma, USA) was used. HaCaT cells and NIH3T3 cells were inoculated in a 35 mm culture dish at 1 × 10 ⁵ cells, respectively, and then 1,5-isoquinoline diol (0.1, 1, 10 μM) was added and incubated for 6 hours. UV irradiation of 60 mJ / cm ^2, and removing the cell death after 12 hours and then washing the remaining cells on the bottom dish with phosphate buffered saline (PBS), 0.2 % in PBS the cells at room temperature, glutaraldehyde and 2 % Formaldehyde for 15 minutes. Then, the cells were washed with PBS and fixed cells were incubated with 1 mg / mL X-gal staining solution (5-bromo-4-chloro-3-indolyl beta-D-galactopyranoside) at 37 ° C for 24 hours. Thereafter, the number of blue-stained cells was calculated using an optical microscope using a 200X objective lens. The measurements were taken at four different fields of view and averaged, and the results are shown in FIG.

As can be seen from Fig. 3, it was confirmed that beta-galactosidase was inhibited by the concentration of 1,5-isoquinoline diol even upon UV irradiation.

Example 4. Inhibition of collagenase activity

The degree of inhibition of collagenase activity was measured to confirm the skin aging inhibitory effect. Collagenase type 1 was used and the substrate was FALGPA (N- (3- [2-Furyl] acryloyl) -Leu-Gly-Pro-Ala). 30 μl of 1,5-isoquinoline diol, 10 μl of collagenase, and 60 μl of tricine buffer were reacted at 37 ° C for 20 minutes, followed by addition of 20 μl of substrate and further reaction for 20 minutes. The absorbance was then measured at 340 nm. The collagenase inhibitory activity was expressed as the absorbance reduction rate of the sample solution and the no-added solution. EGCG (epigallocatechin gallate, 10 μM) was used as a positive control.

As can be seen in FIG. 4A, inhibition of collagenase by HaCaT cells and NIH3T3 cells was significantly observed depending on the concentration of 1,5-isoquinoline diol.

Example 5 Elastinase Inhibition

The amount of p-nitroanilide produced was measured at 37 ° C for 30 minutes using N-succinyl- (L-Ala) 3-p-nitroanilide as a substrate to confirm the effect of wrinkle improvement. Activity was confirmed. 0.05 ml of an elastinase, pancreatic solution (Type I: derived from pancreas, 0.6 units / ml) dissolved in 50 mM Tris-HCl buffer (pH 8.6) was added to 0.1 ml of 1,5-isoquinoline diol, 0.1 ml of N-succinyl- (L-Ala) 3-p-nitroanilide (1 mg / ml) dissolved in 50 mM Tris-HCl buffer (pH 8.6) was added and reacted at 37 ° C for 30 minutes. The absorbance was then measured at 410 nm using a microplate reader. Elastinase inhibitory activity was expressed as the absorbance reduction ratio of the sample solution and the non-added sample. As a positive control, ursolic acid 250 μg / ml was used.

As can be seen in Figure 4b, inhibition of elastinase was significantly observed in both HaCaT and NIH3T3 cells depending on the concentration of 1,5-isoquinoline diol.

The present invention has been described with reference to the preferred embodiments. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is defined by the appended claims rather than by the foregoing description, and all differences within the scope of equivalents thereof should be construed as being included in the present invention.

Claims (9)

1,5-isoquinoline diol or a pharmaceutically acceptable salt thereof as an active ingredient. 2. The composition of claim 1, wherein the 1,5-isoquinoline diol is at a concentration of 0.1 [mu] M to 10 [mu] M. The composition according to claim 1, wherein the composition has an antioxidative effect and a photoaging inhibitory effect. The composition according to claim 1, wherein the 1,5-isoquinoline diol is contained in an amount of 0.001 to 30% by weight based on the total weight of the cosmetic composition. The cosmetic composition according to claim 1, wherein the cosmetic composition is a solution, suspension, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing oil, powder foundation, emulsion foundation, wax foundation, Lt; RTI ID = 0.0 > of: < / RTI > 1,5-isoquinoline diol or a pharmaceutically acceptable salt thereof as an active ingredient. 7. The composition of claim 6, wherein the composition inhibits photoaging of the scalp to prevent hair loss. 7. The composition of claim 6, wherein the 1,5-isoquinoline diol is in a concentration of 0.1 μM to 10 μM. The composition according to claim 6, wherein the 1,5-isoquinoline diol is contained in an amount of 0.001 to 30% by weight based on the total weight of the composition for preventing hair loss.

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