JP2017078061A - Scalp agents - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide means to soften the scalp, and to provide materials that suppress collagen overproduction by fibroblasts.MEANS FOR SOLVING THE PROBLEM: We found that Aspalathus linearis, Ginkgo biloba, Oryza sativa, Curcuma longa, Citrus unshiu, Coptis japonica, Uncaria gambir, Rubus, Cinchona, Sophora angustifolia, Cinnamomum cassia, Geranium thunbergii, Crataegus cuneata Sieb.et Zucc., Zingiber officinale, Hypericum perforatum, Aesculus hippocastanum, Rosa centifolia, Syzygium aromaticum, Rubus suavissimus, Houttuynia cordata, Rosa multiflora Thunb, hamamelis, Plectranthus japonicus, Fucus, Vitis, Humulus lupulus, Morus alba, Eucalyptus, Betula pubescens and Sanguisorba officinalis have excellent overproduction inhibition effect of collagen, and completed the present invention. The scalp softening agent containing the collagen overproduction inhibitor of the present invention can be provided as a cosmetic product, a quasi-drug, a medical product or the like.SELECTED DRAWING: Figure 2

Description

  The present invention relates to a scalp softener comprising a collagen overproduction inhibitor.

  Collagen produced by fibroblasts is important for maintaining skin elasticity. However, when fibroblasts are stimulated by inflammation such as TGF-β due to inflammation, collagen production becomes excessive and fibrosis characterized by collagen deposition and fibroblast proliferation occurs (Non-patent Document 1). Fibrotic skin loses flexibility and hardens (Non-patent Document 1).

  TGF-β1 is also known as a hair loss factor secreted from hair follicle dermal papilla cells (Patent Document 1). TGF-β1 also increases when fibroblasts are stimulated with male hormones and enhances collagen production (Non-patent Document 2). Actually, in the scalp of a male pattern baldness patient, fibrosis is observed around the hair follicle in the hair loss region (Patent Document 2, Non-Patent Documents 3 to 5). The fibrotic region becomes a physical barrier for hair follicle elongation, and the treatment responsiveness of the hair growth agent is reduced (Non-Patent Document 4), the blood flow of the scalp is decreased, the activity of hair matrix cells is decreased (Patent Document 2) ) Is suggested. Therefore, development of the component which prevents or improves the fibrosis of a scalp and softens the scalp is anticipated (patent document 2).

  In order to soften the scalp, it is effective to suppress the abnormal accumulation of collagen and eliminate fibrosis (Patent Document 2). Until now, in order to soften the scalp, a method of infiltrating steam into the stratum corneum of the skin has been performed (Patent Document 3), but the method of infiltrating steam does not necessarily have an action of inhibiting collagen overproduction. is not. In addition, for example, anti-inflammatory drugs have been used for the treatment of fibrotic tissues (Non-patent Document 6). However, the anti-inflammatory component does not necessarily have an anti-fibrotic effect (Non-patent Document 7), and the fibrosis prevention or improvement effect of known anti-inflammatory components is not sufficient. Pirfenidone is an anti-fibrotic drug, which improves fibrosis by suppressing collagen overproduction of fibroblasts stimulated with TGF-β1 (Non-patent Document 8). However, from the viewpoint of side effects, development of safer ingredients is desired.

JP2004-248632. Patent No. 2869168. JP2013-244079.

Yokozaki, Y. et al. General Health Science. 2012 28: 81-86. Yoo HG. Et al. Biol Pharm Bull. 2006 29 (6): 1246-1250. Mahe YF. Et al. Int J Dermatol. 2000 39 (8): 576-584. Hideo Uno. Clinical and research. 2000 77: 1117-1124. Sueki H. et al. Acta Derm Venereol. 1999 79 (5): 347-350. Tatsuya Okamoto, Takashi Tsujimori. Journal of Japanese Society of Internal Medicine 2005 94 (6): 1075-1081. Okuji, Shigenobu Semori. Separate volume BIO Clinica 2011 26 (12): 50-55. Drug interview form Pirfenidone tablets `` Pirespa tablets 200 mg ''.

  An object of the present invention is to provide a material that suppresses collagen overproduction of fibroblasts. Furthermore, it is providing the raw material which suppresses the collagen overproduction of the fibroblast of the hair follicle part of a scalp. Another object of the present invention is to provide a scalp softening agent containing a collagen overproduction inhibitor.

  In order to solve the above-mentioned problems, the inventors have conducted intensive studies, and as a result, asparagus linen alice, ginkgo, rice, turmeric, unshimikan, auren, gambel, raspberry, linden, clara, cinani silicate, geno shoko, hawthorn, ginger, hypericum perforatum. At least one kind of plant selected from the group consisting of: horse chestnut, rose, clove, tencha, dokudami, rose, clam, tomato, shiba, grape, hop, mugwa, eucalyptus, birch and walnut It has been found that it has an overproduction inhibitory action, and the present invention has been completed.

That is, the present invention
(1) Asparagus Linea Alice, Ginkgo, Rice, Turmeric, Satsuma Mandarin, Auren, Gambirium, Raspberry, Kinera, Clara, Sinanikei, Genpoko, Hawthorn, Ginger, Hypericum perforatum, Horse Chestnut, Rose of Rose, Clove, Tencha, Rose A collagen overproduction inhibitor characterized by containing at least one plant selected from the group consisting of: Hamelis, Hikikoshi, Hibamata, grapes, hops, mugwa, eucalyptus, European birch and walnut mulberry, or an extract thereof,
(2) The collagen overproduction inhibitor according to (1), which is applied to the scalp,
(3) A scalp softener comprising the collagen overproduction inhibitor according to (1) or (2),
(4) Based on a collagen overproduction inhibitor or a collagen overproduction inhibitory action, using as an index the addition of a test substance to fibroblasts whose collagen production increased by TGF-β stimulation and suppressing collagen overproduction A method for screening scalp softener,
It is.

  According to the present invention, a collagen overproduction inhibitor and a scalp softener containing the same can be provided.

FIG. 1 shows the amount of collagen produced in Test Example 1, and shows the amount of collagen produced by the TGF-β1 stimulation group and the amount of collagen produced by the non-stimulation group. Fig. 2 shows asparagus linen alice, ginkgo, turmeric, mandarin orange, auren, ganbeeroki, raspberry, linden, clara, gentian, hawthorn, hypericum perforatum, horse chestnut, rose, tencha, green rose, hamamelis, hikimoko, grape, hibamata, grape It is the figure which showed the collagen overproduction inhibitory effect of the extract (solvent: 0.1% 1, 3- butylene glycol) of a hop, a mugwa, a eucalyptus, a European birch, and a bitumen. FIG. 3 is a diagram showing the collagen overproduction inhibitory effect of rice and dokudami extract (solvent: 0.3% 1,3-butylene glycol). FIG. 4 is a diagram showing the collagen overproduction inhibitory effect of Cinani silicate and ginger extract (solvent: 0.1% ethanol). FIG. 5 is a diagram showing the collagen overproduction inhibitory effect of clove extract (solvent: 0.5% ethanol).

  Asparagus Linea Alice, Ginkgo, Rice, Turmeric, Unshimikan, Auren, Gambirium, Raspberry, Kinaki, Clara, Cinnamon, Genius, Hawthorn, Ginger, Hypericum perforatum, Horse Chestnut, Rose Rose, Clove, Tencha, Dokudami, Table 1 shows the scientific names and sites of use of Neubara, Hamamelis, Hikikoshi, Hibamata, grapes, hops, mugwa, eucalyptus, European birch, and bituminous. Although each site | part used for this invention can use arbitrary site | parts, it is preferable to use the site | part described in Table 1. FIG.

  Each plant used in the present invention may be, for example, a powdery dried product obtained by further finely pulverizing a dried chopped product, or an extracted extract, but it is preferable to use an extracted extract. The plant extract of the present invention may be extracted by any method, for example, water, lower aliphatic alcohol (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohol (propylene glycol, 1,3-butylene glycol, glycerin). , Dipropylene glycol and the like), and an extract extracted with a solvent such as a lower aliphatic ketone (acetone and the like) can be used.

  When the plant of the present invention is extracted with a solvent composed of water and ethanol, the ethanol content in the solvent is preferably 30 to 90% by volume, and when extracted with a solvent composed of water and 1,3-butylene glycol, the solvent The content of 1,3-butylene glycol is preferably 30 to 70% by volume.

  In addition, the form of the plant extract of the present invention is not particularly limited, and dry extract powder, extract powder, soft extract, fluid extract, etc. can be used by heat treatment, freeze drying or reduced pressure drying. . In addition, none of the plant extracts used in the present invention is known about the collagen overproduction inhibitory action or scalp softening action of the present invention.

  The collagen overproduction inhibitor of the present invention can be provided as a cosmetic, quasi-drug, or pharmaceutical product. The dosage form is for external application applied to the scalp. In addition, it can be used as a reagent.

  Examples of the dosage form when the present invention is applied externally include shampoos, conditioners, lotions, liquids, creams, ointments, gels, sprays, soaps and the like. These can be produced by known methods. In production, various additives that can be contained in cosmetics, quasi-drugs, pharmaceuticals, or reagents can be blended within a range that does not impair the effects of the present invention.

  Further, the collagen overproduction inhibitor of the present invention includes assembly extract, carrot extract, capsicum tincture, ginger tincture, loquat leaf extract, glycyrrhetinic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, pantothenic acid, panthenol, vitamin E and its Derivatives, hinokitiol, salicylic acid, piroctone olamine, minoxidil, adenosine, t-flavanone, cytopurine, pentadecanoic acid glyceride, allantoin, and nicotinic acid amide can also be used in combination.

  The blending amount of the plant or plant extract of the present invention is 0.000001 to 10% by mass, preferably 0.0001 to 5% by mass, more preferably, when provided as a cosmetic, quasi-drug, pharmaceutical or reagent. 0.001 to 1% by mass.

  In addition, the present invention provides a method for screening an excellent collagen overproduction inhibitor, and also provides a method for screening a scalp softener based on a collagen overproduction inhibitory action.

  The present invention adds a test substance or material to fibroblasts stimulated with TGF-β to enhance collagen production, and suppresses collagen overproduction as an index, and is used as a collagen overproduction inhibitor or collagen overproduction. This is a method for screening a scalp softener based on an inhibitory action. The scalp softener screened by the present invention is based on a new mechanism of action that suppresses overproduction of collagen by TGF-β stimulation and softens the scalp.

  Although a test example is given to the following and this invention is demonstrated more concretely, this invention is not limited to a test example.

(Test Example 1) Evaluation of collagen overproduction inhibitory action on human fibroblasts stimulated with TGF-β1 <Test method>
Human fibroblasts (Kurashikibo Co., Ltd.) were seeded in a 96-well plate at a density of 1 × 10 ⁴ cells / hole and pre-cultured for 24 hours in an incubator set at 37 ° C. and 5% CO ₂ . FibroLife BM basal medium (Kurashikibo Co., Ltd.) containing serum (2% by volume), L-glutamine and penicillin / streptomycin was used as the medium. After the preculture, the cell surface was washed with PBS, and then the medium was added as follows. A serum-free medium containing a solvent was added to the unstimulated group so that the final concentration of the solvent (1,3-butylene glycol or ethanol) was the same as that of each plant extract group. To the TGF-β1 stimulation (control) group, TGF-β1 (10 ng / mL) was added to enhance collagen production, and the final concentration of the solvent (1,3-butylene glycol or ethanol) was different from that of each plant extract group. A serum-free medium with a solvent added so as to be identical was added. To each plant extract group, a plant extract (10 μg / mL) was added as a material for evaluating the collagen overproduction inhibitory effect, and a serum-free medium added with TGF-β1 (10 ng / mL) was further added. After changing the medium, the cells were cultured for 72 hours. Thereafter, the medium was collected and used for measurement of collagen production. M-PER Mammalian Protein Extraction Reagent (Thermo Fisher Scientific Co., Ltd.) was added to the cells after collecting the medium, and the cell lysate was collected and used for the measurement of cell protein mass. Collagen production was measured using a Procollagen type I C-peptide (PIP) EIA Kit (Takara Bio Inc.) according to the instructions in the instruction manual. Cell protein mass was measured using a BCA protein assay reagent kit (Thermo Fisher Scientific Co., Ltd.) according to the instructions in the instruction manual. The measured value of collagen production was the amount of PIP per mass of cell protein (ng / μg protein). From the measured value of the amount of collagen production in each hole, the average value and standard error of 3 holes in each group were calculated. The final concentrations of 1,3-butylene glycol and ethanol were both 0.5% by volume or less so as not to be toxic to cells.

<Result>
FIG. 1 is a graph showing collagen production in the TGF-β1 stimulation (control) group and collagen production in the non-stimulation group. The measured value of collagen production (ng / μg protein) was 12.35 ± 0.62 in the unstimulated group, 26.79 ± 0.69 in the TGF-β1 stimulated (control) group, and the collagen production was significant in the TGF-β1 stimulated (control) group. Increase was observed.
2-5 is a figure which showed the collagen excessive production inhibitory effect of each plant extract of this invention. In FIG. 2, the collagen overproduction suppression effect is shown as a relative value (average value ± standard error) of the collagen production amount of each plant extract group, with the collagen production amount of the TGF-β1 stimulation (control) group as 100% ( Solvent: 0.1% 1,3-butylene glycol). The measured value (ng / μg protein) of collagen production in the TGF-β1 stimulation (control) group shown in FIG. 1 is 26.79 ± 0.69, and the collagen production in the TGF-β1 stimulation (control) group is 100%. It is shown in FIG. As is clear from FIG. 2, each plant extract showed an effect of suppressing collagen overproduction.
In FIG. 3, the collagen overproduction inhibitory effect is shown as a relative value (average value ± standard error) of the collagen production amount of each plant extract group, assuming that the collagen production amount of the TGF-β1 stimulation (control) group is 100% ( Solvent: 0.3% 1,3-butylene glycol). As is clear from FIG. 3, the rice and dokudami extracts showed the effect of inhibiting collagen overproduction. The measured value of collagen production (ng / μg protein) is 8.77 ± 0.08 (ng / μg protein) in the non-stimulated group and 12.97 ± 1.11 (ng / μg protein) in the TGF-β1 stimulated (control) group. In the TGF-β1-stimulated (control) group, a significant increase in collagen production was observed.
In FIG. 4, the collagen overproduction inhibitory effect is shown as a relative value (average value ± standard error) of collagen production in each plant extract group, with the collagen production in the TGF-β1 stimulation (control) group being 100% ( Solvent: 0.1% ethanol). As is clear from FIG. 4, the extract of Sinanikei and ginger showed an effect of suppressing collagen overproduction. The measured value of collagen production (ng / μg protein) was 7.12 ± 0.81 in the unstimulated group, 13.63 ± 1.13 in the TGF-β1 stimulation (control) group, and collagen production in the TGF-β1 stimulation (control) group. A significant increase was observed.
In FIG. 5, the collagen overproduction inhibitory effect is shown as a relative value (average value ± standard error) of the collagen production amount of each plant extract group, assuming that the collagen production amount of the TGF-β1 stimulation (control) group is 100% ( Solvent: 0.5% ethanol). As is clear from FIG. 5, the clove extract showed an inhibitory effect on collagen overproduction. The measured value of collagen production (ng / μg protein) was 8.59 ± 0.26 in the unstimulated group, 12.77 ± 1.54 in the TGF-β1 stimulation (control) group, and collagen production in the TGF-β1 stimulation (control) group. Increased.

  Table 2 shows the test results. Each plant extract significantly suppressed collagen production of fibroblasts compared to the TGF-β1 stimulation (control) group.

  From the above results, asparagus linen alice, ginkgo, rice, turmeric, unshimikan, auren, ganbei, kistrawberry, linden, clara, cinnamon kei, genus shochu, hawthorn, ginger, hypericum perforatum, horse chestnut, rose rose, clove, tencha, dokudami It has been clarified that the extract of Neubara, Hamamelis, Hikikoshi, Hibamata, grape, hop, mugwa, eucalyptus, European birch or walnut mushroom has an effect of suppressing collagen overproduction in fibroblasts. Based on the results of this test, the collagen overproduction inhibitor of the present invention, when applied to the hair follicle of the scalp, is considered to suppress excessive collagen production of fibroblasts by TGF-β stimulation. , Rice, turmeric, mandarin orange, auren, ganbeioki, raspberry, linden, clara, cinnanikkei, genus shochu, hawthorn, ginger, hypericum periwinkle, horse chestnut, rose, choji, tencha, dokudami, nebara, hamamelis, hibiko, grape It is speculated that hop, mugwa, eucalyptus, European birch and bitumen extract have a scalp softening effect.

  Asparagus Linea Alice, Ginkgo, Rice, Turmeric, Citrus unshiu, Auren, Gambirium, Raspberry, Kinaki, Clara, Cinnaike, Gentian pepper, Hawthorn, Ginger, Hypericum perforatum, Horse chestnut, Rose rose, Clove, Tencha, Red rose , Hamamelis, Hikikoshi, Hibamata, grapes, hops, mugwa, eucalyptus, European birch and valerian extract have the effect of suppressing excessive collagen production of fibroblasts, especially those caused by TGF-β stimulation, thus softening the scalp It can be used in the fields of cosmetics, quasi-drugs, pharmaceuticals and the like. Further, the scalp softening agent containing the collagen overproduction inhibitor of the present invention can be used as a positive control agent when performing material screening or the like.

Claims (3)

  Asparagus Linea Alice, Ginkgo biloba, Rice, Turmeric, Citrus unshiu, Auren, Gambirium, Raspberry, Kinera, Clara, Sinanikei, Gentian Ginger, Hawthorn, Ginger, Hypericum perforatum, Pteropia japonica, Rose, Clove, Tencha, Butterflies, Wildflower A collagen overproduction inhibitor characterized by containing at least one plant selected from the group consisting of hikiokoshi, hibamata, grapes, hops, mugwa, eucalyptus, european birch, and bitumen, or an extract thereof.   The collagen overproduction inhibitor according to claim 1, which is applied to the scalp. A scalp softening agent comprising the collagen overproduction inhibitor according to claim 1 or 2.

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