JP6908968B2 - Topical skin anti-wrinkle agent and sRAGE production promoter in fibroblasts - Google Patents

Description

The present invention relates to an external preparation for skin, and more particularly to an external preparation for skin containing a component that prevents skin aging.

In recent years, glycation is said to be the cause of various diseases including diabetes. Glycation is a phenomenon in which proteins and excess sugars bind to each other in the body to denature and deteriorate the proteins. When the glycation reaction proceeds, AGEs (advanced glycation end products) are finally produced. (Generation of AGEs).

In addition, AGEs form crosslinks between AGEs or between AGEs and biological proteins (crosslink formation of AGEs). Then, the crosslinked AGEs aggregate and are less likely to be decomposed (suppression of decomposition of AGEs).

In particular, as an effect on the skin, glycation of proteins constituting skin tissue such as keratin, collagen, and elastin causes aging (wrinkles, dullness, etc.) of the skin. Therefore, it is important to develop an external preparation for skin containing a component (anti-glycation component) for preventing skin aging due to saccharification.

External skin preparations containing anti-glycation components are widely used. Such external preparations for skin are disclosed, for example, in JP-A-2003-212794 (Patent Document 1) and JP-A-2011-246353 (Patent Document 2).

Patent Document 1 discloses an AGEs production inhibitor and a skin external preparation containing the same. More specifically, Patent Document 1 discloses an AGEs production inhibitor composed of one or more components such as a plant extract of the genus Peony, a plant extract of the genus Skullcap, and an extract of the genus Melissa. ..

Further, as a plant of the genus Peony (Paeonia L.), a button (Paeonia sufruticosa Andr.) And a peony (Paeonia lactiflora Pall.) Are exemplified as preferable examples.

Further, Patent Document 2 discloses an AGEs decomposing agent suitable for an external preparation for skin such as a whitening cosmetic. More specifically, in Patent Document 2, the AGEs decomposing agent includes not only a component having an action of decomposing the produced AGEs but also a component having an action of suppressing the formation of AGEs. The AGEs decomposing agent is described as, for example, a component that cleaves the CC bond (crosslink formation) of the α-diketone of AGEs. As the AGEs decomposing agent, plants of the genus Olive of the family Oleaceae, the genus Saxifraga of the family Saxifraga, and the genus Potentilla of the family Rosaceae are exemplified.

Japanese Unexamined Patent Publication No. 2003-212794 Japanese Unexamined Patent Publication No. 2011-246353

The above-mentioned Patent Document 1 and Patent Document 2 describe a component that suppresses the formation of AGEs and a component that cuts the cross-linking of AGEs. However, in Patent Document 1 and Patent Document 2, there is no disclosure or suggestion of a component that suppresses the formation of crosslinks of AGEs. Therefore, in Patent Documents 1 and 2, the components (anti-glycation components) for preventing aging due to saccharification are insufficient, and it is desired to develop a component capable of suppressing the formation of crosslinks of AGEs.

Therefore, in view of such circumstances, the inventors have obtained new findings regarding a component capable of suppressing the formation of crosslinks of AGEs as a result of repeated diligent studies. An object of the present invention is to provide an external preparation for skin that prevents skin aging due to glycation and more effectively improves wrinkles and dullness by containing a component that suppresses the formation of crosslinks of AGEs.

The external preparation for skin of the present invention is characterized by containing a component that suppresses the formation of crosslinks of AGEs.

According to the external preparation for skin having the above constitution, since the component that suppresses the cross-linking formation of AGEs is contained, the component that suppresses the cross-linking formation of AGEs suppresses the cross-linking formation of AGEs, thereby facilitating the decomposition of AGEs and saccharification. It is possible to prevent skin aging due to (advanced glycation end formation of AGEs) and more effectively improve wrinkles and dullness.

As one aspect of the present invention, the component that suppresses the cross-linking formation of the AGEs is preferably magnesium aspartate, zinc gluconate, or copper gluconate.

According to the external preparation for skin having the above constitution, the components that suppress the cross-linking formation of AGEs are magnesium aspartate, zinc gluconate, and copper gluconate. Therefore, these components suppress the cross-linking formation of AGEs, thereby AGEs. Is easily decomposed, aging of the skin due to glycation (crosslink formation of AGEs) can be prevented, and wrinkles and dullness can be improved more effectively.

As another aspect of the present invention, it is preferable to further contain a component that suppresses the formation of the AGEs.

According to the external preparation for skin having the above constitution, since the component that suppresses the production of AGEs is further contained, the component that suppresses the production of AGEs prevents the skin from aging due to the increase in the production of AGEs, and makes wrinkles and dullness more effective. Can be improved.

As yet another aspect of the present invention, it is preferable to further include a component that cleaves the crosslinks of the AGEs.

According to the external preparation for skin having the above constitution, since the component that cleaves the crosslink of AGEs is further contained, even if the crosslink of AGEs is formed, the crosslink of AGEs is cleaved by the component that cleaves the crosslink of AGEs, and the AGEs are decomposed. It is possible to prevent skin aging due to an increase in cross-linking formation of AGEs (suppression of decomposition of AGEs) and to improve wrinkles and dullness more effectively.

As yet another aspect of the present invention, it is preferable that the component that suppresses the production of the AGEs is at least one selected from the group consisting of the pecan shell extract and the peanut seed coat extract.

According to the external preparation for skin having the above constitution, the component that suppresses the production of AGEs is at least one selected from the group consisting of pecan shell extract and lacquer seed coat extract, and therefore any one of these components is used. By suppressing the production of AGEs, it is possible to prevent skin aging due to an increase in the production of AGEs and to more effectively improve wrinkles and dullness.

As yet another aspect of the present invention, it is preferable that the component that cleaves the crosslinks of the AGEs contains a peony root extract.

According to the external preparation for skin having the above constitution, the component that cleaves the crosslinks of AGEs contains a crosslink of AGEs. Therefore, even when the crosslinks of AGEs are formed, the crosslinks of AGEs are cleaved by the crosslinks of AGEs, and AGEs are released. It becomes easy to be decomposed, aging of the skin due to an increase in cross-linking formation of AGEs (suppression of decomposition of AGEs) can be prevented, and wrinkles and dullness can be improved more effectively.

As yet another aspect of the present invention, magnesium aspartate, zinc gluconate, copper gluconate as components that suppress the cross-linking formation of the AGEs, and pecan shell extract and peanut seed coat as components that suppress the formation of the AGEs. It preferably contains at least one selected from the group consisting of extracts.

According to the external preparation for skin having the above constitution, magnesium aspartate, zinc gluconate, and copper gluconate suppress the formation of crosslinks of AGEs, and at least one of them selected from the group consisting of pecan shell extract and lacquer seed coat extract. By one, the production of AGEs is suppressed, the aging of the skin due to saccharification (crosslinking of AGEs and the production of AGEs) can be prevented, and wrinkles and dullness can be improved more effectively.

As yet another aspect of the present invention, magnesium aspartate, zinc gluconate, copper gluconate as components that suppress the cross-linking formation of the AGEs, and pecan shell extract and lacquer seed coat as components that suppress the formation of the AGEs. It is preferable to include at least one selected from the group consisting of extracts and a syrup root extract as a component for cleaving the cross-linking of the AGEs.

According to the external preparation for skin having the above constitution, magnesium aspartate, zinc gluconate, and copper gluconate suppress the formation of crosslinks of AGEs and at least one selected from the group consisting of pecan shell extract and lacquer seed coat extract. By one, the production of AGEs is suppressed, and the cross-linking of AGEs is cleaved by the sardine root extract, thereby preventing skin aging due to glycation (cross-linking of AGEs, production of AGEs and suppression of decomposition of AGEs), and wrinkles. The dullness can be improved even more effectively.

As described above, according to the present invention, it is possible to obtain an excellent effect such as being able to provide an external preparation for skin that prevents aging of the skin due to saccharification and more effectively improves wrinkles and dullness.

Hereinafter, the external preparation for skin according to the embodiment of the present invention will be described in detail.

The external preparation for skin according to the present embodiment is for preventing skin aging due to saccharification and more effectively improving wrinkles and dullness.

As described above, the inventors have obtained new findings regarding a component capable of suppressing the formation of crosslinks of AGEs. Therefore, the inventors have constructed a new anti-glycation theory for the mechanism of anti-glycation. More specifically, the inventors classified the anti-glycation mechanism into three major steps, and considered the components in each step. That is, the anti-glycation mechanism is classified into the following steps.

Step (A) ... Suppresses the formation of AGEs.

Step (B) ... Suppresses the formation of crosslinks between AGEs or between AGEs and proteins.

Step (C) ... Cleaves the crosslinks between the produced AGEs or between the AGEs and the protein.

Then, by including components related to the three steps in anti-glycation of the skin (a component that suppresses the formation of crosslinks of AGEs, a component that suppresses the formation of AGEs, and a component that cuts the crosslinks of AGEs), aging due to saccharification is prevented. , Wrinkles and dullness of the skin will be improved more effectively.

The external preparation for skin according to the present embodiment contains a component that suppresses the formation of crosslinks of AGEs (step (B)).

In the present embodiment, the components that suppress the cross-linking formation of AGEs are magnesium aspartate, zinc gluconate, and copper gluconate.

More specifically, in the external preparation for skin according to the present embodiment, SEPITONIC M3 (manufactured by SEPPIC), which contains magnesium aspartate, zinc gluconate, and copper gluconate as active ingredients as components that suppress the formation of crosslinks of AGEs. Is used. The manufacturer names and ingredients of the products are shown in Table 1 below. The results of screening experiments for components that suppress the formation of crosslinks of AGEs will be described later.

Among the products containing an ingredient that suppresses the cross-linking formation of AGEs as an active ingredient, SEPITONIC M3 harmlessly converts RAGE (advanced glycation end receptor), which causes cell death, inflammation, and abnormal collagen / elastin accumulation, into AGEs. It has been found that it converts to bindable sRAGE (solvable RAGE) and promotes the production of sRAGE.

RAGE is a transmembrane receptor that is present in various cells and is present on the surface of the cell membrane. AGEs bind to the extracellular region of RAGE existing on the surface of the cell membrane and transmit various information into the cell via RAGE.

The SEPITONIC M3 cuts the extramembrane region of the RAGE to generate the sRAGE. Then, it is considered that the generated sRAGE binds to AGEs to suppress the formation of crosslinks between AGEs or between AGEs and proteins.

The external preparation for skin according to the present embodiment further contains a component that suppresses the production of AGEs (step (A)).

In the present embodiment, the component that suppresses the production of AGEs is at least one selected from the group consisting of pecan shell extract and peanut seed coat extract.

More specifically, in the external preparation for skin according to the present embodiment, pecan nut extract BG (manufactured by Nichiyu Co., Ltd.) and peanut seed coat extract containing pecan shell extract as an active ingredient as containing an ingredient that suppresses the production of AGEs. A nut peel extract (manufactured by Katakura Chikkarin Co., Ltd.) containing the above as an active ingredient is used. The manufacturer name and ingredients of each product are shown in Table 2 below. The results of screening experiments for components that suppress the production of AGEs will be described later.

The external preparation for skin according to the present embodiment further contains a component that cleaves the crosslinks of AGEs (step (C)).

In the present embodiment, the component that cleaves the crosslinks of AGEs includes peony root extract.

More specifically, in the external preparation for skin according to the present embodiment, a peony liquid (manufactured by Ichimaru Falcos) containing a peony root extract as an active ingredient is used as a component containing a component that cleaves the crosslinks of AGEs. The manufacturer names and ingredients of the products are shown in Table 3 below. The results of screening experiments for components that cleave the crosslinks of AGEs will be described later.

In the present embodiment, the peony liquid is considered to cleave the crosslinks between the produced AGEs or between the AGEs and the protein.

Alternatively, in the present embodiment, magnesium aspartate, zinc gluconate, copper gluconate, and sardine root extract as a component that cleaves the cross-linking of AGEs can be included as a component that suppresses the formation of crosslinks of AGEs.

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.
<(1) Ingredients that suppress the formation of AGEs>

[Screening of components that suppress the production of AGEs]
(Screening method)
First, a glucose-added solution was prepared for each of the screening targets as follows. More specifically, the screening target was placed in a mixed solution of 100 μl of 4 mg / ml bovine serum albumin (manufactured by Wako Pure Chemical Industries, Ltd.), 250 μl of 100 μM sodium hydrogen phosphate (manufactured by Wako Pure Chemical Industries, Ltd.), and 90 μl of purified water. After addition so that the final concentration was 2%, 50 μl of 2M glucose (manufactured by Wako Pure Chemical Industries, Ltd.) was added. Next, the prepared glucose-added solution was saccharified by reacting at 60 ° C. for 24 hours. To 100 μl of each reaction solution, 10 μl of trichloroacetic acid (manufactured by Wako Pure Chemical Industries, Ltd.) was added and stirred, and the resulting precipitate was separated and then dissolved in an alkaline phosphate buffer solution (manufactured by Wako Pure Chemical Industries, Ltd.). The fluorescence intensity of the solution was measured using PowerScan HT (manufactured by Sumitomo Dainippon Pharma, Inc.) at an excitation wavelength of 360 nm and a fluorescence wavelength of 460 nm.

In this screening, the amount of fluorescent AGEs, FFI (2- (2-fluoroyl) -4 (5)-(2-furanyl) -1H-imidazole), was evaluated as an index of the amount of AGEs. The FFI production inhibition rate was calculated from the fluorescence intensity of FFI obtained by PowerScan HT (saccharification inhibition rate). The saccharification inhibition rate is 0% for a sample (positive control) that has undergone a saccharification reaction without adding a screening target. In addition, in order to eliminate the influence of fluorescence absorption (quenching effect) by the screening target itself, the quenching rate was measured by measuring the FFI amount of the quenching evaluation sample in which 2 μl of the screening target was added to 98 μl of the saccharification reaction solution of the positive control. Was calculated. Then, by subtracting the quenching rate from the FFI production inhibition rate, this was set as the true glycation inhibition rate.

(Screening result (AGEs production suppression rate))
Screening experiments were performed using the method described above. The results are shown in Table 4.

As a result of diligent examination, among the screening targets, pecan nut extract BG (manufactured by NOF Corporation) and nut peel extract (manufactured by Katakura Chikkarin) have a suppression rate of 50% or more (about 69% and about 50%, respectively). showed that.

In addition, when considering whether there is a common ingredient among the above-mentioned two ingredients showing an AGEs production suppression rate of 50% or more, pecan nut extract BG (manufactured by Nichiyu Co., Ltd.): active ingredient ( Pecan husk extract) and nut peel extract (manufactured by Katakura Chikkarin Co., Ltd.): There was no common ingredient among the active ingredients (laccasei seed coat extract).

Therefore, it is considered that each of the pecan shell extract and the peanut seed coat extract has an action as a component that suppresses the production of AGEs.
<(2) Components that suppress the formation of crosslinks of AGEs>

[SRAGE AGEs crosslink formation inhibitory effect evaluation test (collagen gel contraction activity experiment)]
(Collagen gel production)
Specifically, a collagen gel was prepared on a 12-well microplate using a collagen gel culture kit (manufactured by Nitta Gelatin). Next, 700 μl of 100 mM glucose 6-phosphate (manufactured by Sigma-Aldrich) and 63 μl of 200 μg / mls RAGE were added to each of the prepared collagen gels, and the mixture was reacted at 37 ° C. for 10 to 14 days.
(Measurement of collagen gel area)
After the reaction, the prepared collagen gel was washed with PBS (-), and normal human fetal skin-derived fibroblasts were seeded on the ^{collagen gel at 4.5 × 10 4 cells / well.} After 1 hour, the collagen gel was separated from each well, and after another 2 hours, the area of each collagen gel was measured. The contractile activity of each collagen gel was obtained by setting the contractile activity of the collagen gel of the control group (without addition of glucose 6-phosphate) to 100%. The results are shown in Table 5.

(Measurement result of collagen gel area)
As shown in Table 5, the contractile activity of the collagen gel supplemented with glucose 6-phosphate was reduced to about 78% as compared with the control group. On the other hand, in the collagen gel to which glucose 6-phosphate and sRAGE were added, the decrease was suppressed to about 95% as compared with the control group.

From the above results, in the collagen gel to which sRAGE was added, the added sRAGE bound to AGEs to block the cross-linking formation and structural abnormality of collagen due to AGEs, and good collagen gel contraction activity was obtained. it is conceivable that.

[Experiment of suppressing lysozyme binding of sRAGE to AGEs-formed elastin]
When AGEs are produced in elastin, AGEs-formed elastin easily binds to lysozyme and is less susceptible to the effects of elastin-degrading enzymes. As a result, it is known that elastin aggregates abnormally and deposits on the skin (J Invest Dermatol. 2012 Feb; 132 (2): 315-23). The inventors argued that the action of sRAGE on AGEs-ized elastin may suppress the binding between AGEs and lysozyme. Therefore, the effect of sRAGE on lysozyme binding to AGEs-modified elastin was verified according to the following experimental method. The results are shown in Table 6.

(experimental method)
The experimental protocol for the lysozyme binding inhibition experiment of sRAGE for AGEs-modified elastin is as follows.

100 μl of 2 mg / ml soluble elastin (manufactured by Wako Pure Chemical Industries, Ltd.) was added to a 96-well ELISA plate (manufactured by Nunc) and reacted at 4 ° C. overnight to immobilize elastin on the plate. After removing the excess solution, 100 μl of 0.2M ribose (manufactured by Tokyo Chemical Industry Co., Ltd.) was added and reacted at 37 ° C. for 2 weeks to prepare elastin AGEs. After 2 weeks, ribose was removed, washed with PBS (−), 10 μg or 20 μg of sRAGE was added, and the mixture was reacted at room temperature for 1 hour. After removing sRAGE and washing with PBS (−), 10 μg of lysozyme was reacted at room temperature for 1 hour. Then, it was washed with PBS (−), and the lysozyme antibody (manufactured by AbD Serotec) was subjected to a primary antibody reaction at room temperature for 1 hour. The cells were washed with PBS-T, and Goat anti-mouse IgG was subjected to a secondary antibody reaction at room temperature for 1 hour. Further, it was washed with PBS-T, and the color-developing reagent TMB (3,3', 5,5'-tetramethylbenzine) (manufactured by Sigma-Aldrich) was reacted for 30 minutes with 2N sulfuric acid (manufactured by Wako Pure Chemical Industries, Ltd.). The reaction was stopped. Absorbance was measured and evaluated with A450 / A630.

(Experimental result)
The amount of lysozyme bound was suppressed to 83% when 10 μg of sRAGE was added as compared with the case where sRAGE was not added (control group). Furthermore, when 20 μg of sRAGE was added, it was suppressed to 75%.

From the above results, it was shown that the binding of sRAGE to AGEs suppresses the binding of AGEs and lysozyme in elastin. It is considered that AGEs-modified elastin is normally metabolized by degrading enzymes without being affected by lysozyme by sRAGE, and as a result, the decrease in skin elasticity due to abnormal aggregation of elastin is suppressed.

[Screening of components that suppress the formation of crosslinks of AGEs (sRAGE production promoting components)]
(Screening method)
1. 1. Culturing of Mouse Fetal Derived Fibroblast Cell Strain (NIH3T3) Mouse fetal derived fibroblast cell line (NIH3T3) was cultured in Dulvecco's Modified Eagle's Medium (DMEM) medium (manufactured by Thermo Fisher Scientific).
2. Measurement of the amount of sRAGE in the culture supernatant The cultured cells in the DMEM medium described above were collected by trypsin treatment ^{, seeded on a 96-well microplate at 3 × 10 3} cells / well, and cultured in the DMEM medium for 24 hours. Subsequently, using Lipofectamine 2000 (manufactured by Thermo Fisher Scientific) and Opti-MEM medium (manufactured by Thermo Fisher Scientific), the RAGE plasmid (manufactured by Thermo Fisher Scientific) and the RAGE plasmid (manufactured by HMG Biotech) and the transfection of the pmaxGFP plasmid (manufactured by Lonza) were simultaneously transfected. Incubated for 5 hours. Then, the medium was replaced with DMEM medium, and the cells were cultured for another 24 hours. Each screening target was added at a predetermined concentration of 0.05 to 0.1%, cultured for 24 hours, and then the culture supernatant was collected, and the amount of sRAGE in the culture supernatant obtained above was measured by Human RAGE Quantikine. The measurement was performed using an ELISA Kit (manufactured by R & D). The amount of sRAGE showed a value corrected by the amount of intracellular GFP. The results are shown in Table 7.

(Screening result of sRAGE production promoting component (sRAGE production promoting effect))
As a result of diligent examination, a remarkable sRAGE production promoting effect was observed in SEPITONIC M3 (manufactured by SEPPIC) (about 175%) among the screening subjects.
<(3) Components that cleave the crosslinks of AGEs>

[Screening of components that cleave the crosslinks of AGEs]
(Collagen gel production)
First, a collagen gel was prepared on a 12-well microplate using a collagen gel culture kit (manufactured by Nitta Gelatin). Next, 700 μl of 100 mM glucose 6-phosphate (manufactured by Sigma-Aldrich) was added to the prepared collagen gel and reacted at 37 ° C. for 30 days to prepare a glycated collagen gel.

(Measurement of collagen gel area)
After 30 days, the prepared collagen gel was washed with PBS (−). Then, the screening target was added at a predetermined concentration of 1% and reacted at 37 ° C. for 3 days. After 3 days, the screening target was removed, washed with PBS (−), and then normal human fetal skin-derived fibroblasts ^{were seeded at 4.5 × 10 4} cells / well. After 1 hour, the collagen gel was separated from each well, and after another 2 hours, the area of each collagen gel was measured. Each collagen gel contractile activity was obtained by setting the contractile activity of the collagen gel of the control group (without addition of glucose 6-phosphate) to 100%. The results are shown in Table 8.

(Measurement result of collagen gel area)
As shown in Table 8, as a result of diligent examination, a remarkable effect of improving collagen gel contraction activity was observed in peony liquid (manufactured by Ichimaru Falcos) (about 96%). Compared with the control group, the collagen gel to which glucose 6-phosphate was added reduced the contractile activity to about 79%. On the other hand, in the collagen gel to which the peony liquid was further added, the decrease was suppressed to about 96% as compared with the control group.

From the above results, as shown in Table 8, when Shakuya Liquid is added to the collagen gel saccharified with glucose 6-phosphate, the added Shakuya Liquid causes cross-linking between the produced AGEs or between AGEs and proteins. It is considered that good collagen gel contraction activity was obtained by cleavage.

[Combination effect experiment of peony liquid and sRAGE (SEPITONIC M3)]
As described above, in SEPITONIC M3 (manufactured by SEPPIC), a remarkable sRAGE production promoting effect was observed. That is, this component converts RAGE into sRAGE and promotes the production of sRAGE, so that the produced sRAGE binds to AGEs and suppresses the formation of crosslinks between AGEs or between AGEs and proteins. Do you get it.

Further, as described above, the peony liquid cleaved the crosslinks between the produced AGEs or between the AGEs and the protein, and good collagen gel contraction activity was observed.

Therefore, the inventors of the peony liquid and sRAGE to confirm whether the peony liquid can prevent the recrosslinking of AGEs by cleaving the cross-linking of AGEs and promoting the production of sRAGE from RAGE by SEPITONIC M3. The combined effect was carried out by a collagen gel contraction activity experiment.

(Collagen gel contraction activity experiment)
More specifically, a collagen gel was prepared by the same method as described above, and used in a combined effect experiment of peony liquid and sRAGE. Each collagen gel was subjected to the treatments (1) to (6) shown below in Table 9. The results are shown in Table 9.

(1) PBS (-) treatment (control group)
(2) Treatment with glucose 6-phosphate (saccharification treatment)
(3) Treat the saccharified gel (2) with peony liquid (4) After removing the peony liquid from the gel of (3), treat with PBS (5) After removing the peony liquid from the gel of (3), again , Glucose 6-phosphate treatment (reglycation treatment)
(6) After removing the peony liquid from the gel of (3), it was treated with sRAGE and glucose 6-phosphate (collagen gel contraction activity experimental results).
As shown in Table 9, the contractile activity was reduced to 54% when the saccharification treatment was performed as in (2) as compared with the control group treated in (1). Furthermore, by treating the saccharified gel as in (3) with peony liquid, the contractile activity was suppressed to a decrease of about 68%.

Further, as in (4), when the peony liquid was removed from the collagen gel to which the peony liquid was added and replaced with PBS (−), the collagen gel contractile activity was maintained even 4 days after the replacement.

When the AGEs cross-linking was cleaved with peony liquid and then re-glycated with glucose 6-phosphate as in (5), the collagen gel contraction activity decreased from about 68% to 52%. On the other hand, as in (6), by adding sRAGE during the re-glycation treatment, the collagen gel contraction activity was suppressed to a decrease of about 60%.

From the above results, as shown in Table 9, it was confirmed that the recrosslinking of AGEs can be prevented and good collagen contractile activity can be obtained by using sRAGE in combination with the crosslinking and cleavage action of AGEs of the peony liquid. Was done. From this, by using peony liquid and SEPITONIC M3 that promotes the production of sRAGE in combination, AGEs cross-linking in the biological protein is cleaved, and AGEs or AGEs and proteins are prevented from being re-crosslinked due to the effect of sRAGE. It is thought that it can be done.

As described above, according to the external skin preparation according to the present embodiment, magnesium aspartate, zinc gluconate, and copper gluconate suppress the formation of crosslinks of AGEs, so that AGEs are easily decomposed and the crosslinks of AGEs are easily formed. It can prevent skin aging due to formation and more effectively improve wrinkles and dullness.

In addition, at least one selected from the group consisting of pecan shell extract and peanut seed coat extract suppresses the production of AGEs, thereby preventing skin aging due to an increase in the production of AGEs and making wrinkles and dullness more effective. Can be improved.

Further, even when the cross-linking of AGEs is formed, the cross-linking of AGEs is cleaved by the shakuyaku root extract, but excess sugar is always present in the aged skin, and re-cross-linking of AGEs occurs. The combined use of shark root extract and magnesium aspartate, zinc gluconate, and copper gluconate cleaves the crosslinks of AGEs, prevents recrosslinking of AGEs, facilitates the decomposition of AGEs, and increases the formation of crosslinks of AGEs (AGEs). It is possible to prevent skin aging due to (advanced glycation end) and improve wrinkles and dullness more effectively.

It should be noted that the external preparation for skin of the present invention is not limited to the above-described embodiment, and of course, it can be appropriately modified without departing from the gist of the present invention.

In the above embodiment, as a component that suppresses the formation of crosslinks of AGEs, magnesium aspartate, zinc gluconate, copper gluconate, and as a component that suppresses the production of AGEs, it is selected from the group consisting of pecan shell extract and peanut seed coat extract. It is also possible to include at least one of them.

Alternatively, in the above embodiment, as a component that suppresses the formation of crosslinks of AGEs, as a component that suppresses the formation of magnesium aspartate, zinc gluconate, copper gluconate, and as a component that suppresses the production of AGEs, it is selected from the group consisting of pecan shell extract and lacquer seed coat extract. It is also possible to include at least one of the above and a syrup root extract as a component for cleaving the cross-linking of AGEs.

The form of the external preparation for skin according to the present embodiment is not particularly limited, and various forms used for general external preparation for skin, cosmetics, etc. are adopted as long as the effects of the present invention are not impaired. be able to.

For example, the form of the external preparation for skin may be a liquid, a gel, a milky lotion, a cream, an ointment, a semi-solid, an oil gel, a sheet or the like. In addition, for example, oils, pigments, preservatives, surfactants, fragrances, pigments and the like can be appropriately blended according to the dosage form of the external preparation for skin according to the present embodiment.

The external preparation for skin of the present invention is effectively used as an external preparation for skin that more effectively improves wrinkles and dullness of the skin due to saccharification.

Claims (7)

As a component that suppresses the formation of crosslinks of AGEs, an sRAGE production promoter in fibroblasts is provided.
The sRAGE production promoter is a skin external preparation for preventing wrinkles of the skin, which comprises magnesium aspartate, zinc gluconate, and copper gluconate. Further comprising a component to suppress generation of A GES, prevent skin external agent skin wrinkles according to claim 1. Further comprising a component to cut the cross-linking of A GES, prevent skin external agent skin wrinkles according to claim 1 or 2. It said components suppress Generating AGEs is at least any one selected from the group consisting of pecan shells extract and peanut seed coat extract, anti-skin agent for external use skin wrinkles according to claim 2. Component to cut the cross-linking of the AGEs include peony root extract, anti-skin agent for external use skin wrinkles according to claim 3. Wherein at least any one selected from the group consisting of pecan shells extract and peanut seed coat extract for suppressing component Generating AGEs,
As a component for cutting the cross-linking of AGEs including peony root equi scan, prevent skin external agent skin wrinkles according to claim 1. An agent for promoting the production of sRAGE in fibroblasts , which comprises magnesium aspartate, zinc gluconate, and copper gluconate.