JP2014129252A - Skin function improving agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide food products and pharmaceuticals which include extracts of plants of the genus Hibiscus in the family Malvaceae as active ingredients, wherein the food products and pharmaceuticals are MMP-1 production inhibitors, and antiinflammatory agents, and have the action to keep skin firmness and the action to prevent wrinkles, and further are effective in improvement of scleroderma.SOLUTION: This invention provides skin function improving agents, antiinflammatory agents, anti-wrinkle agents, and anti-scleroderma agents which include extracts of plants of the genus Hibiscus in the family Malvaceae as active ingredients.

Description

  The present invention relates to a skin function-improving agent containing an extract of a Mulberry family such as Roselle. More specifically, it contains an extract having an anti-inflammatory action derived from a plant of the family Hyacinthaceae as an active ingredient, maintains skin tension, has an anti-wrinkle effect, and prevents skin disorders such as scleroderma. It relates to an anti-inflammatory agent that improves.

  IL-1β is usually a precursor (proIL-1β) that is present in the cell, but is cleaved by activation of Caspase-1 accompanying inflammasome activation, becomes a mature form, and is secreted outside the cell. Secreted IL-1β acts on various cells to mainly induce Th1-type inflammatory reaction and migration of neutrophils to the infected area. Known diseases caused by an increase in IL-1β include hepatitis, alcoholic hepatitis, spinal cord disease, rheumatoid arthritis and the like.

  It is known that IL-1β production increases due to the stimulation of ultraviolet irradiation, and induces collagenase production (Non-patent Document 1). Collagenase is an enzyme that specifically cleaves collagen protein. It causes skin wrinkles and viscoelasticity due to aging and ultraviolet rays, metabolic diseases such as osteoporosis, epidermolysis varicella, corneal ulcer, root disease, etc. It is involved in many diseases such as arthritic diseases such as rheumatoid arthritis and osteoarthritis. Therefore, these relaxations can be achieved by inhibiting collagenase.

  Especially in collagenase, MMP-1 is an enzyme that degrades type I, II, and III collagens. In recent years, autoantibodies against MMP-1 have emerged in systemic scleroderma and can suppress MMP-1 activity. It has been suggested that the anti-MMP-1 antibody may be involved in fibrosis (Non-patent Document 2). For this reason, suppressing the production of MMP-1 also contributes to disease prevention.

  From the above, many collagenase inhibitors have been developed so far. Collagenase inhibitors based on plant extracts such as lychee seeds and extracts thereof (Patent Document 1) and merbou heartwood extract (Patent Document 2) have been developed. But there is nothing about hibiscus. Regarding hibiscus, hyaluronidase activity inhibitory action and histamine release inhibitory action (Patent Document 3), activation of fibroblast proliferation, promotion of extracellular matrix production (Patent Document 4), and improvement of skin tension and wrinkles Although the effect (Patent Document 5) is known, it is not known to act directly on the activity of collagenase.

  Furthermore, hibiscus flowers are used as cosmetics having an anti-inflammatory effect (Patent Document 6), but only a subjective evaluation and no specific anti-inflammatory effect is shown. Hibiscus is an extremely safe substance with sufficient food experience such that Roselle extract is used as herbal tea.

JP 2003-63926 A JP 2004-269448 A JP-A-9-87188 Japanese Patent Laid-Open No. 9-295928 JP 2005-112742 A JP 2000-7545 A

Hasegawa Ikuo, “Changes in cytoskeleton and membrane proteins of cultured human gingival epithelial cells by addition of IL-1β”, Journal of Japanese Society of Periodontology, Vol. 40, No. 2, 1998, pp. 188-197 Tomimura, Saori; ogawa, Fumihide; Iwata, Yohei; Komura, Kazuhiro; Hara, Toshihide; Muroi, Eiji; Takenaka, Motoi; Shimizu, Kazuhiro; Hasegawa, Minoru; Fujimoto, Manabu; Sato, Shinichi, "Autoantibodies against matrix metalloproteinase- 1 in patents with localized scleroderma ", Journal of Dermatologic science, 52 (1), 2008, pp. 199 47-54

  The present invention contains an extract of a plant belonging to the family Hyacinthaceae as an active ingredient, and as a MMP-1 production inhibitor and anti-inflammatory agent, as an agent that maintains skin tension and has an anti-wrinkle effect. It aims at providing the pharmaceutical as an agent effective in improvement of dermatosis.

  The present inventors have found that a hibiscus extract has a collagenase inhibitory activity and an anti-inflammatory activity such as skin, and has completed the following invention.

(1) A skin function-improving agent comprising an extract of a plant belonging to the genus Fuaceae as an active ingredient.
(2) The skin function-improving agent according to (1), wherein the extract of a plant belonging to the genus Hyacinthaceae is an extract of Hibiscus sabdariffa.
(3) The skin function-improving agent according to (1) or (2), wherein a plant belonging to the genus Hyacinth is a flower part extract.

(4) The skin function-improving agent according to any one of items (1) to (3), which contains the extract of the plant of the genus Hyacinthaceae as a collagenase production-suppressing component.
(5) The skin function according to any one of (1) to (3), wherein the extract of the plant belonging to the genus Hyacinthaceae is contained as a production inhibitory component of MMP-1 (matrix metalloproteinase-1). Improver.

(6) The skin function-improving agent according to any one of (1) to (3), which contains an extract of the plant belonging to the genus Hyacinthaceae as an anti-inflammatory component.

(7) The skin according to any one of items (1) to (3), which contains the extract of the plant of the genus Hyacinthaceae as a component that maintains skin tension and suppresses the generation of wrinkles. Function improver.
(8) The skin function-improving agent according to any one of (1) to (3), which contains an extract of the plant of the genus Hyacinthaceae as an anti-scleroderma component.

(9) A collagenase production inhibitor comprising, as an active ingredient, an extract of the plant of the genus Hyacinthaceae according to any one of items (1) to (3).
(10) An MMP-1 production inhibitor comprising, as an active ingredient, the extract of the plant of the family Mallowaceae according to any one of (1) to (3).

(11) An anti-inflammatory agent comprising, as an active ingredient, the extract of the plant of the genus Hyacinthaceae according to any one of the items (1) to (3).
(12) An anti-wrinkle agent comprising, as an active ingredient, the extract of the plant of the genus Hyacinthaceae according to any one of (1) to (3).
(13) An anti-scleroderma agent comprising, as an active ingredient, the extract of the plant of the genus Hyacinthaceae according to any one of the above items (1) to (3).

  According to the present invention, there is provided a pharmaceutical composition containing an anti-inflammatory active substance derived from a natural product as an active ingredient. The composition of the present invention has collagenase production inhibitory activity, has an effect of maintaining skin tension and suppressing the generation of wrinkles, and can be expected to have an effect of preventing and improving scleroderma.

It is a figure which shows an example of the MMP-1 production inhibitory effect of the extract of this invention.

The present invention relates to a skin function-improving agent having an anti-inflammatory action, which comprises an extract of a plant of the family Hyacinthaceae as an active ingredient.
The plant of the genus Hyacinthus used in the skin function improving agent having anti-inflammatory action of the present invention is Roselle (Hibiscus sabadariffa).

  The method for producing the extract of the plant belonging to the genus Hyacinthaceae used in the present invention is not particularly limited. For example, it can be obtained by heat-sterilizing the plant of the family Hyacinthaceae and extracting with hot water. it can. In addition, it can be obtained by employing water extraction and ethanol extraction. The extract can be used as a liquid as it is or in a liquid state that is further concentrated to contain the active ingredient in a high content, and can also be used in the state of being dried to a solid.

  The extract of the plant of the family Hyacinthaceae has an excellent anti-inflammatory action, in particular, an anti-inflammatory action on the skin. Therefore, administration of an effective amount of a plant extract of the genus Hyacinthaceae can promote an anti-inflammatory effect particularly on the skin. The skin function-improving agent of the present invention containing an extract of a plant belonging to the genus Hyacinthaceae as an active ingredient can be used as a pharmaceutical or food (pharmaceutical composition or food composition) itself, It can be used as an active ingredient of a food composition.

  In the present invention, the term “anti-inflammatory action” refers to the action of suppressing the production of collagenase induced by stimulation of the cytokine IL-1β in the living body, in particular, the production of MMP-1 to suppress inflammation caused by the enzyme. Is included. Therefore, the skin function-improving agent of the present invention is useful as a component of pharmaceuticals and foods that suppress collagenase production, in particular, suppress MMP-1 production, maintain skin tension and prevent wrinkles. It is also useful as an active ingredient in foods or pharmaceuticals for improving scleroderma.

  For example, the skin function improving agent of the present invention such as an anti-inflammatory agent for skin can be formulated according to a conventional method. The preparation may be a solid preparation or a liquid preparation. Examples of such preparations include tablets, pills, granules, dragees, capsules, emulsions, solutions, gels, syrups, slurries, suspensions, and the like. Moreover, in formulation, additives, such as an excipient | filler, can be added as needed on a formulation. As the excipient, fillers, binders, coagulants, slipping agents, disintegrating agents, pigments, sweeteners, fragrances, coating agents and the like can be used alone or in combination depending on the purpose.

  The content of the extract of the plant of the genus Hyacinthaceae in the skin function improving agent having anti-inflammatory action of the present invention varies depending on the form of the preparation, but is usually 0.01 to 90% by mass with respect to the whole preparation, Preferably it is 1-70 mass%, More preferably, it is 5-50 mass%.

  In the case where the extract of the plant of the genus Hyacinthaceae having the anti-inflammatory action of the present invention is constituted as a food, there is no particular limitation on the aspect thereof, in addition to general processed food, health food, functional food, concentrated liquid food , Foods and drinks including nutritional supplements, beverages and foods, or additives thereof. Specifically, an extract of a plant belonging to the genus Hyacinthaceae can be added to supplements and soft drinks, but is not particularly limited. In addition, the extract of the plant belonging to the genus Hyacinth may be added to the food as it is, or may be processed and added as a raw material of the food.

  Examples of the form of the food of the present invention include liquid, gel, powder, and solid foods. Specific examples of the food of the present invention include beverages (sports drinks, tea, soups, etc.), jelly beverages, yogurt, frozen yogurt, seasonings (dressing, mayonnaise, sprinkles, miso, soy sauce, grilled meat sauce, etc.), noodles, Processed livestock fish, processed food (ham, sausage, etc.), jam, dairy products (milk, cream, butter, cheese, margarine, etc.), bread, confectionery (jelly, ice cream, sorbet, pudding, etc.) It is not limited to.

  A food containing an extract of a plant of the genus Hyacinthaceae may contain other additives depending on the form of the food. Examples of such additives include excipients, extenders, binders, moisture-proofing agents, preservatives, reinforcing agents, thickeners, emulsifiers, food additives, seasonings and the like. Examples of food additives include vitamins, minerals, chitin, chitosan, lecithin, royal jelly and the like. Examples of the seasoning include sweeteners such as granulated sugar, honey, and sorbit; alcohols; acidulants such as citric acid, malic acid, and aragonic acid; fragrances; pigments, and the like. Can be used to adjust. Moreover, you may use together the well-known raw material relevant to the objective of this invention.

  The food containing the extract of the plant of the genus Hyacinthaceae of the present invention can be produced by a method usually performed by those skilled in the art. For example, in order to obtain a food in powder form, an excipient such as dextrin, cyclodextrin, starch, maltose, etc. is added to the extract of the plant of the family Hyacinthaceae as needed, and then freeze-dried, spray-dried, etc. It can obtain by making it powder by the drying method. In addition to excipients, vitamins, minerals, fats and oils of animals and plants, fish and shellfish, proteins, carbohydrates, pigments, fragrances, and other edible additives can be further added as necessary.

  The food containing the extract of the plant of the genus Hyacinthaceae of the present invention may be combined with other physiologically active substances or health food materials. Examples of such substances include green juice, healthy vinegar, healthy tea, royal jelly, aloe, blueberry, propolis, isoflavone, noni, nucleic acid, garlic, turmeric, enzyme, ginseng, millet, natto, ginkgo biloba, germinated brown rice , Maca, Meshimakobu, Grape Seed, Spirulina, Tomorrow, Fucoidan, Oyster, Horse Oil, Mulberry Leaves, Salacia, Hanabiratake, Tabuchi Carrot, Cassis, Shijimi, Kikuimo, Collagen, Chlorella, Glucosamine, Chitosan, Carnitine, CoQ10, Ceramide And octacosanol.

  The extract of the plant of the family Hyacinthaceae is an extremely safe substance with sufficient eating experience. Since the plants of the genus Aoiaceae are widely distributed as edible herbs, it is considered that the intake of the food of the present invention is not strictly limited. The lower limit of the intake amount is set to the minimum amount that can exert an effect according to the purpose, and the upper limit can be set on the basis of an actual amount from the viewpoint of ease of intake, economy, and the like. In the case of oral administration, usually about 10 mg to about 5 g, preferably about 10 mg to about 1 g, of an extract of the plant of the family Hyacinthaceae may be taken per day for an adult. Of course, it can also be changed according to the age, weight, symptom, duration of treatment, course of treatment, etc. of the person who takes it. The daily dose can be taken in several divided doses.

  When the extract of the plant of the genus Hyacinthaceae of the present invention is constituted as a pharmaceutical product, in one embodiment, the pharmaceutical product is suitably formulated for oral administration. A formulation suitable for oral administration is a solution obtained by dissolving an effective amount of an extract of a mallow family plant in a dilute solution such as water or physiological saline, and an effective amount of an extract of an Mallow family plant. Capsules, granules, powders or tablets contained as solids or granules, suspensions in which an effective amount of the extract of a mallow family plant is suspended in an appropriate dispersion medium, an effective amount of a mallow family An emulsion or the like in which a solution in which an extract of a genus plant is dissolved is dispersed in an appropriate dispersion medium and emulsified.

  In the pharmaceutical product of the present invention, the dose of the extract of the plant of the genus Hyacinthaceae, which is an active ingredient, varies depending on the administration form, the type of administration subject, the administration route, the administration period, the body weight, the age, etc. It can be made the same range as the amount of food intake. Of course, as described above, the dosage varies depending on various conditions, so that an amount smaller than the above dosage may be sufficient, or it may be necessary to administer beyond the range.

  In the present invention, the inhibitory effect of MMP-1 is shown as an anti-inflammatory index. When it has an excellent MMP-1 inhibitory effect, it can be expected to improve scleroderma caused by anti-MMP-1 antibody in the skin. In addition, it is expected that the effect will be exerted even in combination with existing therapeutic agents.

  EXAMPLES Hereinafter, although an Example and a comparative example demonstrate this invention concretely, the technical scope of this invention is not limited by the following Examples etc. In the following examples and the like, “%” represents “mass%”.

(Preparation of extract)
A hibiscus (Hibiscus sabdariffa) flower (5 g) was sterilized by autoclaving (121 ° C., 20 minutes), extracted with 100 mL of hot water at 80 ° C. for 1 hour, and filtered to obtain an extract. The extract obtained was concentrated by evaporation to prepare a test extract having an evaporation residue of 1%.

<Test example>
The following tests were conducted using human normal dermal fibroblasts (Fibroblasts: RIKEN GENE BANK: NB1RGB).
The number of cells was suspended in a medium (10% FBS-DMEM) so as to have a count of 1 × 10 ⁵ / mL. The cell suspension medium was seeded at 2 mL / well in a 6-well plate and cultured in a 37 ° C., 5% CO ₂ incubator for 24 hours. After the culture, the test extract having the evaporation residue of 1% was added at 50 μL / welI, and further cultured at 37 ° C. in a 5% CO ₂ incubator for 24 hours.
After culture, 50 μL / well of 0.1 μg / mL humanIL-1β (genzyme) was added, and the cells were cultured in a 37 ° C., 5% CO ₂ incubator for 4 hours to induce inflammation.
After culturing, the cells were collected by ISOGEN treatment, and mRNA extraction and cDNA preparation were performed according to a standard method. Then, the expression level of mRNA was quantified by RT-PCR method.
A similar test was performed on test extracts prepared from “lavender” and “jasmine” by the same extraction method as that for the extract from the hibiscus flower.
In addition, as control, control (+) indicates that inflammation is caused in the absence of the test substance (extract), and control (control) indicates that the test substance (extract) is not added and causes no inflammation. -). The results are shown in FIG.
In the statistical processing, after examining the variance by F test, T test was performed.
There was a significant difference at p <0.05.

As shown in FIG. 1, cultured cells to which a test extract obtained from Hibiscus sabdariffa flower was added showed that MMP-1 was in comparison with control (+) even when IL-1β caused inflammation. The expression level of mRNA was suppressed.
This was remarkably suppressed as compared with the case where the test extract prepared from “lavender” and “jasmine” was added.
From this, it can be expected that the extract obtained from hibiscus has an anti-inflammatory effect that suppresses inflammation of human normal skin fibroblasts (NBlRGB) by IL-1β.

  From the above experimental results, the test extract obtained from hibiscus effectively suppresses collagenase production and degrades arthritis and human normal skin fibroblasts (NBlRGB) due to collagen degradation due to increased collagenase production. Prevents dermatitis caused by MMP-1, especially scleroderma caused by MMP-1 and inflammation such as arthritis, and also prevents spontaneous progression of dermatitis such as developed arthritis and scleroderma It is expected to exhibit an effect that promotes recovery.

  As mentioned above, it prevents the onset of human scleroderma, the onset of inflammation such as dermatitis and arthritis, and the occurrence of wrinkles on the skin, and also suppresses the increase in inflammation and wrinkles that occurred after the onset The hibiscus extract of the present invention, which is expected to promote natural healing, prevents the onset of various inflammations such as skin and internal organs caused by the increase in IL-1β in the body, and prevents the progression after the onset to naturally It is useful as an anti-inflammatory component for promoting healing.

In addition, since it is a substance composed of ingredients that have been conventionally drunk as herbal teas, the extract can be formulated as an anti-inflammatory agent for internal use and has various anti-inflammatory effects, wrinkles It is also useful as an additive for health foods that are expected to have a preventive effect.
Furthermore, it is useful as an active ingredient of external preparations and can be expected to be used as an additive for cosmetics.

Claims (6)

  An agent for improving skin function, comprising an extract of a plant of the genus Fuaceae as an active ingredient.   The skin function-improving agent according to claim 1, wherein the extract of a plant of the family Hyacinthaceae is a flower extract of Hibiscus sabdariffa.   The skin function-improving agent according to claim 1 or 2, comprising an extract of the plant belonging to the genus Hyacinthaceae as an ingredient for inhibiting MMP-1 (matrix metalloproteinase-1) production.   The skin function-improving agent according to claim 1 or 2, which contains an extract of the plant of the genus Hyacinthaceae as an anti-inflammatory component.   The skin function-improving agent according to claim 1 or 2, comprising an extract of the plant belonging to the genus Hyacinthae as an anti-wrinkle component.   The skin function-improving agent according to claim 1 or 2, comprising an extract of the plant belonging to the genus Fuaceae as an anti-scleroderma component.

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