JP2021175715A - Ages formation inhibitory composition - Google Patents

Abstract

To provide AGEs formation inhibitory compositions having excellent safety and usability.SOLUTION: AGEs formation inhibitory compositions contain, as an active ingredient, celery extract and rutin.SELECTED DRAWING: None

Description

The present invention relates to a composition for suppressing AGEs formation, and more particularly to an agent for suppressing AGEs formation, particularly an external preparation for suppressing AGEs formation.

AGEs (abbreviation for Advanced Glycation End Products) is a general term for products produced by the glycation reaction of proteins, and is called advanced glycation end products or late glycation products. It has been reported that AGEs accumulate in the body and cause or exacerbate various symptoms related to age-related chronic diseases such as diabetes, arteriosclerosis, and neurological diseases, and their involvement in aging has been pointed out. ing.

FIG. 1 is a cross-sectional view schematically showing the mechanism of hair growth. The dermal papilla cells at the base of the hair send nutrients and hair growth factors that grow the hair to the hair matrix cells. Hair matrix cells are cells that surround the dermal papilla cells and actively undergo cell division to make hair. Therefore, the hair growth factor is firmly received by the hair matrix cells, so that the hair growth is maintained. On the contrary, if the cooperative relationship between the dermal papilla cells and the hair matrix cells is not good, the hair becomes thin.

Our recent research (Non-Patent Document 1) has revealed that when AGEs accumulate at the dermal papilla cells, inflammatory substances that disrupt the cooperative relationship between the two cells emerge from the dermal papilla cells. As a result, cell division of hair matrix cells is impaired and hair growth is suppressed.

Eur J Dermatol. 2015 Jul-Aug; 25 (4): 359-61 Matsui T, Yamagishi S, et al. Immunol Lett. 2015 Oct; 167 (2): 141-6

In such cases, the hair becomes thinner and thinner as a whole, so it seems that AGEs are related to the diffuse thinning hair on the crown (top of the head), which is more common in women. In addition, in order for AGEs to act on dermal papilla cells, AGEs must fit into the keyway existing in the cells. The hole into which these AGEs fit is called the AGEs receptor, and is called RAGE in English. In other words, AGEs were involved not only in wrinkles and sagging, but also in thinning hair.

The present invention solves the above problems, and an object of the present invention is to provide a composition for suppressing the formation of AGEs, which is excellent in safety and usefulness.

The present invention provides a composition for suppressing the formation of AGEs containing celery extract and rutin as active ingredients. The composition containing celery extract and rutin may be hereinafter referred to as "CR2".

In one form, the celery extract is a water extract of celery.

In one form, the ratio of weight of celery to volume of water is 1/5 to 1 / 0.2.

In one form, celery comprises the celery stalk.

The present invention also provides an AGEs formation inhibitor containing any of the above compositions for suppressing AGEs formation.

The present invention also provides the above-mentioned AGEs formation inhibitor, which is an external preparation.

The present invention also provides the above-mentioned AGEs formation inhibitor, which is a shampoo, conditioner or hair restorer.

According to the present invention, a composition for suppressing the formation of AGEs, which is excellent in safety and usefulness, is provided.

It is sectional drawing which shows typically the mechanism of hair growth. It is a graph which showed how the amount of production of AGEs from albumin and glyceraldehyde is changed in the presence of celery extract, rutin, or both. It is a graph which showed how the oxidative stress level by albumin of a human endothelial cell changes in the presence of a celery extract. It is a graph which showed how the RAGE gene expression level by albumin of a human endothelial cell changes in the presence of a celery extract.

<Celery extract>
"Celery" has a scientific name of "Apium graveolens var. Dulce" and is a plant of the Umbelliferae family. Celery is categorized as light-colored vegetables, and roughly classified into four varieties: intermediate varieties, green varieties, yellow varieties, and oriental native varieties. In the present invention, celery stems, leaves, or stems and leaves are used. Celery extract refers to a liquid component obtained by removing a water-insoluble component from the stem or leaf of celery.

The celery extract can be produced by preparing celery as a raw material and performing crushing, squeezing, filtration, solid-liquid separation, and purification if necessary. A solvent may be added to the crushed celery during squeezing. As a result, the liquid component can be efficiently extracted from celery.

As the solvent for extracting the liquid component from celery, water, 1,3-butylene glycol, or another organic solvent can be used (including water containing an organic solvent). Examples of the organic solvent include methanol and ethanol, but a wide range of known organic solvents such as acetone, diethyl ether, ethyl acetate and hexane are included. When water is used as the extraction solvent, a phosphate buffer solution is preferably used from the viewpoint of stabilizing the pH of the obtained celery extract.

For example, a predetermined amount of water is added to a predetermined amount of celery, the celery is crushed with a mixer, filtered and centrifuged, and then a transparent supernatant is collected to obtain a celery extract. The amount of celery and water used is, for example, an amount in which the ratio of the weight of the celery pulverized product to the volume of water is 1/5 to 1 / 0.2. By keeping the amount of celery and water used in this range, the stability of the obtained celery extract is improved. The ratio of the weight of the celery pulverized product to the volume of water is preferably 1/2 to 1 / 0.5, more preferably 1 / 1.5 to 1 / 0.7.

Concentrated celery juice or reduced celery juice may be used as the raw material for the celery extract, thereby eliminating the steps of preparing, crushing and squeezing the celery. A celery extract commercially available as a quasi-drug may be used.

The amount of celery extract used is 0.2 to 5.0% by weight based on the volume of the composition for suppressing AGEs formation. By setting the amount of celery extract used within the above range, the effect of suppressing the formation of AGEs is improved. The amount of the celery extract used is preferably 0.4 to 3.0% by weight, more preferably 0.7 to 2.0% by weight, based on the volume of the composition for suppressing the formation of AGEs.

<Rutin>
Rutin is one of the tasteless and odorless flavonoids widely contained in higher plants, vegetables and fruits, and has the effect of reinforcing and improving the fragile capillaries together with vitamin C for a long time. It is of interest as a natural extract with many functions, including antioxidant activity, and is a proven substance for use as pharmaceuticals and raw materials for pharmaceuticals.

Rutin can be produced, for example, by extracting from a rutin-rich plant such as a sprout of buckwheat. As the rutin, for example, commercially available ones can be used. Rutin may be rutin modified to increase water solubility. Specific examples of such water-soluble rutin include α-glucosylated rutin.

The amount of rutin used is 20 to 500 μM (micromol / liter) based on the volume of the composition for suppressing AGEs formation. By setting the amount of rutin used in the above range, the effect of suppressing the formation of AGEs is improved. The amount of rutin used is preferably 50 to 250 μM, more preferably 80 to 150 μM, based on the volume of the composition for suppressing AGEs formation.

<Composition for suppressing AGEs formation>
The composition for suppressing AGEs formation of the present invention exhibits an excellent effect of suppressing AGEs formation as an AGEs formation inhibitor. The composition for suppressing AGEs formation of the present invention not only suppresses the formation of AGEs in the scalp, but also supports hair growth by suppressing endothelial cell damage and inflammatory reaction due to AGEs already present in the scalp and dermal papilla. .. The composition for suppressing the formation of AGEs of the present invention is extremely useful when it is contained in soaps and cosmetics and used as an external preparation, especially when it is contained in shampoos, rinses and hair growth agents and used as an external preparation. high.

<Regarding the action of CR2 (celery extract + rutin)>
Using quasi-drugs, medicated soap, shampoo, conditioner, depilatory, hair restorer, other medicated cosmetics, axillary odor inhibitor, contraindicated agent, and two ingredients recognized as bathing agents, celery extract and rutin. , AGEs formation inhibitory effect, and oxidative stress production and RAGE gene expression inhibitory effect by AGEs were investigated. First, 50 ml of phosphate buffer was added to 50 g of fresh celery, pulverized with a mixer, filtered with a case, centrifuged, and then a clear supernatant was collected and used as a celery extract in an experiment. Rutin was purchased from Wako Pure Chemical Industries, Ltd. with a purity of 90%.

1) AGEs formation inhibitory effect: 25 mg / ml bovine serum albumin and 2 mM glyceral dehide (reducing sugar) in a 0.2 M phosphate buffer (pH 7.4) solution with a final concentration of 1% celery extract and a final concentration of 100 μM rutin. Incubated at 37 ° C for 1 day in the absence of. Then, the sample was dialyzed against a phosphate buffer, and the amount of AGEs-ized albumin was measured by the ELISA method using a monoclonal antibody against AGEs as previously reported (Reference: Non-Patent Document 2). The 50% inhibition concentration of AGEs-ized albumin on the standard curve was defined as 1 U.

Results: When AGEs derived from glyceraldehyde were specifically measured by the ELISA method, the formation of AGEs tended to be suppressed by the administration of rutin and celery extract alone, but the effect was statistical. Was not significant. However, it was found that the formation of AGEs was significantly suppressed in the coexistence of the final concentration of 1% celery extract and the final concentration of 100 μM rutin (Fig. 2, N = 5 in each group, the result was mean ± standard deviation. Statistics. Was analyzed by the Student t test. *, P <0.05).

2) Oxidative stress production in endothelial cells and action on induction of expression of RAGE gene, which is an AGEs receptor After treatment with control albumin (hereinafter referred to as albumin), oxidative stress production was analyzed 30 minutes later, and RAGE gene expression was analyzed 4 hours later by the fluorescent reagent method and the RT-PCR method, respectively.

Results: It was clarified that 1% celery extract suppressed the production of oxidative stress by AGEs and the induction of RAGE gene expression in endothelial cells (Figs. 3 and 4, oxidative stress was N = 12 in each group, RAGE gene). Expression was N = 5 in each group, results were mean ± standard deviation. Statistics were analyzed by Student t test. *, P <0.05, **, p <0.01, albumin + 2 mM glyceraldide (1 day)) ..

<Discussion>
In this study, it was revealed for the first time in the world that the formation of AGEs was significantly suppressed by combining two quasi-drugs, celery extract and rutin (CR2). Furthermore, it was shown that celery extract reduces the reactivity to AGEs in endothelial cells through antioxidant and RAGE expression inhibitory effects. From the above, it is considered that CR2 not only suppresses the formation of AGEs in the scalp, but also suppresses the endothelial cell damage and inflammatory reaction caused by AGEs already present in the scalp and dermal papilla to support hair growth. .. Considering the adverse effects on beauty such as wrinkles, age spots, and thinning hair of AGEs-RAGE, CR2 is expected to be a combination of ingredients that are extremely useful as shampoo / rinse and hair restorer.

The amount of celery extract used is 0.2 to 5.0% by weight based on the weight of the composition for suppressing AGEs formation. By setting the amount of celery extract used within the above range, the effect of suppressing the formation of AGEs is improved. The amount of the celery extract used is preferably 0.4 to 3.0% by weight, more preferably 0.7 to 2.0% by weight, based on the volume of the composition for suppressing AGEs formation.

Claims (7)

A composition for suppressing the formation of AGEs containing celery extract and rutin as active ingredients. The composition for suppressing the formation of AGEs according to claim 1, wherein the celery extract is a water extract of celery. The composition for suppressing AGEs formation according to claim 1 or 2, wherein the ratio of the weight of celery to the volume of extracted water is 1/5 to 1 / 0.2. The composition for suppressing the formation of AGEs according to any one of claims 1 to 3, wherein the celery contains a celery stem. An AGEs formation inhibitor containing the composition for suppressing AGEs formation according to any one of claims 1 to 4. The AGEs formation inhibitor according to claim 5, which is an external preparation. The AGEs formation inhibitor according to claim 5, which is a shampoo, conditioner or hair restorer.

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