JP7421463B2 - Scalp preparation - Google Patents

Description

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

Collagen produced by fibroblasts is important for maintaining skin elasticity. However, when fibroblasts are stimulated by TGF-β or the like due to inflammation, collagen production becomes excessive, resulting in fibrosis characterized by collagen deposition and fibroblast proliferation (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 dermal papilla cells of hair follicles (Patent Document 1). TGF-β1 also increases when fibroblasts are stimulated with male hormones and enhances collagen production (Non-Patent Document 2). In fact, in the scalps of patients with androgenetic alopecia, fibrosis is observed around the hair follicles in the hair loss area (Patent Document 2, Non-Patent Documents 3 to 5). The fibrotic area acts as a physical barrier to hair follicle elongation, resulting in decreased treatment response to hair growth agents (Non-Patent Document 4), decreased blood flow in the scalp, decreased activity of hair matrix cells, etc. (Patent Document 2). ). Therefore, the development of a component that prevents or improves scalp fibrosis and softens the scalp is expected (Patent Document 2).

In order to soften the scalp, it is effective to suppress abnormal accumulation of collagen and eliminate fibrosis (Patent Document 2). Until now, methods have been used to infiltrate the stratum corneum of the skin with steam in order to soften the scalp (Patent Document 3), but methods of infiltrating steam do not necessarily have the effect of suppressing collagen overproduction. isn't it. Furthermore, anti-inflammatory drugs, for example, have been used to treat fibrotic tissues (Non-Patent Document 6). However, anti-inflammatory components do not necessarily have anti-fibrotic effects (Non-Patent Document 7), and the effects of known anti-inflammatory components to prevent or improve fibrosis are not sufficient. Pirfenidone is an anti-fibrotic drug that improves fibrosis by suppressing collagen overproduction in TGF-β1-stimulated fibroblasts (Non-patent Document 8). However, from the viewpoint of side effects, it is desired to develop even safer ingredients.

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

Yasuyuki Yokozaki et al. Comprehensive 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 Suga. Journal of the Japanese Society of Internal Medicine 2005 94(6):1075-1081. Okukushi, Shigenobu Semori. Bessatsu BIO Clinica 2011 26(12):50-55. Pharmaceutical Interview Form Pirfenidone Tablets ``Pirespa Tablets 200mg''.

An object of the present invention is to provide a material that suppresses collagen overproduction by fibroblasts. Another object of the present invention is to provide a material that suppresses collagen overproduction by fibroblasts in the hair follicles of the scalp. Another object of the present invention is to provide a scalp softener containing a collagen overproduction inhibitor.

In order to solve the above problems, the inventors conducted extensive studies and found that asparagus linearis, ginkgo biloba, rice, turmeric, mandarin orange, orientalis, gambier tree, raspberry, cinchona, clara, chinensis, cinchona, hawthorn, ginger, St. John's wort , horse chestnut, Japanese rose, clove, tencha, Houtodyami, Japanese rose, Hamamelis, Hikiokoshi, Fucus, grape, hop, Magwa, eucalyptus, European birch, and Komori, or extracts of these plants have excellent collagen. They discovered that it has an effect of suppressing overproduction, leading to the completion of the present invention.

That is, the present invention
(1) Aspalathus linearis, ginkgo, rice, turmeric, mandarin orange, orensis, gambier tree, bramble, cinchona, clara, chinensis, genus shoko, hawthorn, ginger, hypericum perforatum, horse chestnut, western rose, clove, tencha, dokudami, wild rose , a collagen overproduction inhibitor characterized by containing at least one plant selected from the group consisting of hamamelis, fucus, fucus, grape, hop, magwa, eucalyptus, European birch, and ficus spp., or an extract thereof;
(2) The collagen overproduction inhibitor according to (1), which is applied to the scalp;
(3) A scalp softener containing the collagen overproduction inhibitor according to (1) or (2);
(4) Adding a test substance to fibroblasts whose collagen production has increased due to TGF-β stimulation, and using inhibition of collagen overproduction as an indicator, based on a collagen overproduction inhibitor or collagen overproduction inhibitory effect. How to screen scalp softeners,
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 collagen production amount in Test Example 1, and is a diagram showing the collagen production amount in the TGF-β1 stimulation group and the collagen production amount in the non-stimulation group. Figure 2 shows aspalathus linearis, ginkgo, turmeric, mandarin orange, orientalis, gambier tree, bramble, cinchona, clara, genus shoko, hawthorn, hypericum perforatum, horse chestnut, horse chestnut, rose, tencha, wild rose, hamamelis, hikiokoshi, fucus, grape, FIG. 2 is a diagram showing the collagen overproduction inhibitory effects of hop, magwa, eucalyptus, European birch, and silverypsum extracts (solvent: 0.1% 1,3-butylene glycol). FIG. 3 is a diagram showing the inhibitory effect of rice and Houtyami extract (solvent: 0.3% 1,3-butylene glycol) on collagen overproduction. FIG. 4 is a diagram showing the effect of suppressing collagen overproduction of extracts (solvent: 0.1% ethanol) of Cinnamon chinensis and ginger. FIG. 5 is a diagram showing the inhibitory effect of clove extract (solvent: 0.5% ethanol) on collagen overproduction.

Aspalathus linearis, ginkgo, rice, turmeric, mandarin orange, orensis, gambier tree, bramble, cinchona, clara, chinensis, perforatum, hawthorn, ginger, hypericum perforatum, horse chestnut, western rose, clove, tencha, dokudami, Table 1 shows the scientific names and used parts of Japanese rose, Hamamelis, Hikiokoshi, Fucus, grape, hop, Magawa, Eucalyptus, European birch, and Ficus spp. Although any part of each plant used in the present invention can be used, it is preferable to use the parts listed in Table 1.

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

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

Further, the form of the plant extract of the present invention is not particularly limited, and dry extract powder, extract powder, soft extract, liquid extract, etc. can be used by processing such as heat treatment, freeze drying, or vacuum drying. . Note that none of the plant extracts used in the present invention is known to have the collagen overproduction suppressing effect or scalp softening effect of the present invention.

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

Examples of dosage forms for external application of the present invention include shampoos, conditioners, lotions, liquids, creams, ointments, gels, sprays, and soaps. These can be manufactured by known methods. During production, various additives that can be included in cosmetics, quasi-drugs, pharmaceuticals, or reagents can be blended within a range that does not impair the effects of the present invention.

Furthermore, the collagen overproduction inhibitor of the present invention includes Jasmine japonica extract, carrot extract, capsicum tincture, ginger tincture, loquat leaf extract, glycyrrhetinic acid, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, pantothenic acid, panthenol, vitamin E and its It can also be used in combination with hair growth substances including derivatives, hinokitiol, salicylic acid, piroctone olamine, minoxidil, adenosine, t-flavanone, cytopurin, pentadecanoic acid glyceride, allantoin, nicotinamide.

When provided in cosmetics, quasi-drugs, pharmaceuticals, or reagents, the 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, and more preferably 0.000001 to 5% by mass based on the entire composition. It is 0.001 to 1% by mass.

The present invention also provides a method for screening for an excellent collagen overproduction inhibitor, and also provides a method for screening a scalp softener based on its collagen overproduction inhibitory effect.

The present invention uses a collagen overproduction inhibitor or collagen overproduction by adding a test substance or material to fibroblasts that have been stimulated with TGF-β to increase collagen production, and using the inhibition of collagen overproduction as an indicator. This is a method of screening scalp softeners based on their inhibitory effects. The scalp softeners screened by the present invention are based on a new mechanism of action that suppresses collagen overproduction caused by TGF-β stimulation and softens the scalp.

The present invention will be explained in more detail by giving test examples below, but the present invention is not limited to the test examples.

(Test Example 1) Evaluation of inhibitory effect on collagen overproduction on TGF-β1 stimulated human fibroblasts <Test method>
Human fibroblasts (Kurashiki Boseki Co., Ltd.) were seeded in a 96-well plate at a density of 1×10 ⁴ cells/well, and precultured for 24 hours in an incubator set at 37° C. and 5% CO ₂ . The medium used was FibroLife BM basal medium (Kurashiki Boseki Co., Ltd.) containing serum (2% by volume), L-glutamine, and penicillin/streptomycin. After preculture, the cell surface was washed with PBS, and then a 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 stimulated (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. Serum-free medium with added solvent was added to make the same amount. To each plant extract group, a plant extract (10 μg/mL) was added as a material for evaluating the inhibitory effect on collagen overproduction, and a serum-free medium containing TGF-β1 (10 ng/mL) was added. After replacing the medium, the cells were cultured for 72 hours. Thereafter, the culture medium was collected and used to measure collagen production. After collecting the medium, M-PER Mammalian Protein Extraction Reagent (Thermo Fisher Scientific Co., Ltd.) was added to the cells to collect a cell lysate, which was used to measure the amount of cellular protein. The collagen production amount was measured using Procollagen type I C-peptide (PIP) EIA Kit (Takara Bio Inc.) according to the instructions in the instruction manual. The amount of cellular protein was measured using a BCA protein reagent kit (Thermo Fisher Scientific Co., Ltd. assay) according to the instructions in the instruction manual. The collagen production amount was measured as the amount of PIP per amount of cellular protein (ng/μg protein). The average value and standard error of three wells in each group were calculated from the measured value of collagen production in each well. 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.

<Results>
FIG. 1 is a diagram showing the amount of collagen produced in the TGF-β1 stimulated (control) group and the amount of collagen produced in the non-stimulated group. The measured value of collagen production (ng/μg protein) was 12.35 ± 0.62 in the unstimulated group and 26.79 ± 0.69 in the TGF-β1 stimulated (control) group, indicating a significant increase in collagen production in the TGF-β1 stimulated (control) group. An increase was observed.
FIGS. 2 to 5 are diagrams showing the effect of each plant extract of the present invention on suppressing collagen overproduction. In Figure 2, the collagen overproduction inhibitory effect is shown as the relative value (mean value ± standard error) of the collagen production amount of each plant extract group, with the collagen production amount of the TGF-β1 stimulated (control) group set as 100% ( Solvent: 0.1% 1,3-butylene glycol). The measured value (ng/μg protein) of collagen production in the TGF-β1 stimulated (control) group shown in Figure 1 was 26.79 ± 0.69, taking the collagen production of the TGF-β1 stimulated (control) group as 100%. It is shown in Figure 2. As is clear from FIG. 2, each plant extract exhibited the effect of suppressing collagen overproduction.
In Figure 3, the collagen overproduction inhibitory effect is shown as the relative value (mean value ± standard error) of the collagen production amount of each plant extract group, with the collagen production amount of the TGF-β1 stimulated (control) group set as 100% ( Solvent: 0.3% 1,3-butylene glycol). As is clear from FIG. 3, the extracts of rice and Houtyami showed an effect of suppressing collagen overproduction. The measured value of collagen production (ng/μg protein) was 8.77 ± 0.08 (ng/μg protein) in the unstimulated group and 12.97 ± 1.11 (ng/μg protein) in the TGF-β1 stimulated (control) group. , a significant increase in collagen production was observed in the TGF-β1 stimulated (control) group.
In Figure 4, the effect of suppressing collagen overproduction is shown as the 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 stimulated (control) group set as 100% ( Solvent: 0.1% ethanol). As is clear from FIG. 4, the extracts of Cinnamon chinensis and ginger exhibited the effect of suppressing collagen overproduction. The measured value of collagen production (ng/μg protein) was 7.12 ± 0.81 in the non-stimulated group and 13.63 ± 1.13 in the TGF-β1 stimulated (control) group, indicating that collagen production was significantly lower in the TGF-β1 stimulated (control) group. A significant increase was observed.
In Figure 5, the effect of suppressing collagen overproduction is shown as the 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 stimulated (control) group set as 100% ( Solvent: 0.5% ethanol). As is clear from FIG. 5, the clove extract showed an effect of suppressing collagen overproduction. The measured value of collagen production (ng/μg protein) was 8.59 ± 0.26 in the unstimulated group and 12.77 ± 1.54 in the TGF-β1 stimulated (control) group. An increase in the number of patients was observed.

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

From the above results, Aspalathus linearis, Ginkgo biloba, rice, turmeric, Citrus mandarin orange, Oriental japonica, Gambir tree, Rubus, Cinchona, Clara, Chinese Nikkei, Gennoshoko, Hawthorn, Ginger, St. John's wort, Horse chestnut, Western rose, Clove, Tencha, Hokudyami. It has been revealed that extracts of , Japanese rose, hamamelis, cypress, fucus, grape, hop, magwa, eucalyptus, European birch, or silver moth have the effect of suppressing collagen overproduction in fibroblasts. Based on the results of this test, the collagen overproduction inhibitor of the present invention is thought to inhibit excessive collagen production by fibroblasts stimulated by TGF-β when applied to scalp hair follicles. , rice, turmeric, mandarin orange, orientale, gambier tree, raspberry, cinchona, clara, chinensis, genus shoko, hawthorn, ginger, hypericum perforatum, horse chestnut, rose, clove, tencha, dokudami, wild rose, hamamelis, hikiokoshi, fucus, grape Extracts of , hops, magwa, eucalyptus, birch, and silverberry are thought to have a scalp softening effect.

Aspalathus linearis of the present invention, ginkgo, rice, turmeric, mandarin orange, orensis, gambier tree, bramble, cinchona, clara, chinensis, genus shoko, hawthorn, ginger, hypericum perforatum, horse chestnut, western rose, clove, tencha, dokudami, wild rose Extracts of Hamamelis, Hikiokoshi, Fucus, Grape, Hop, Magwa, Eucalyptus, Birch, and Cucumber have the effect of suppressing excessive collagen production by fibroblasts, especially that caused by TGF-β stimulation, so they soften the scalp. It can be used in the fields of cosmetics, quasi-drugs, or pharmaceuticals to transform the product. Further, the scalp softener containing the collagen overproduction inhibitor of the present invention can be used as a positive control drug when performing material screening and the like.

Claims (2)

A collagen overproduction inhibitor characterized by containing Citrus mandarin orange or its extract as an active ingredient (However, (1) hair growth serum dipotassium glycyrrhizinate with the following formulation, carrot extract, Japanese cabbage extract, orange juice, orange oil, Yuzu extract, Unshu tangerine peel extract, orange peel extract, loquat leaf extract, Oshimazakura leaf extract, aloe extract, ethoxylated hydrogenated castor oil (hydrolyzed), lemongrass extract, orange flower water, peppermint oil, water, butylene glycol, Sodium citrate, glucosylhesperidin, phenoxyethanol, alcohol,
and 2) Conditioner with the following formulation: piroctone olamine, water, cationized guar gum-2, lipase, bentonite, glycerin (cosmetic grade), citric acid, cetearyl alcohol, hydrogenated polyisobutene (hydrolyzed), panthenol, palmitic acid Cetyl, phenoxyethanol, polyglyceryl diisostearate, l-menthol, eucalyptus oil, peppermint oil, orange oil, dipentaerythrityl (hydroxystearate/isostearate), cetrimonium bromide, ilopropyl alcohol, betaine lauryldimethylaminoacetate, sodium chloride, birch Extract, alcohol, citrus fruit, butylene glycol, mandarin orange peel extract, cherry leaf extract, Japanese japonica extract, carrot extract, cetanol, stearyl alcohol, octadecyloxypropyltrimethylammonium chloride, capsicum tincture, parabens,
except for). The collagen overproduction inhibitor according to claim 1, which is applied to the scalp.