Type i collagen production promoter and oral agent in normal human gingival fibroblast

Abstract

To provide type I collagen production promoters with high safety in normal human gingival fibroblasts having excellent type I collagen production promoting action in normal human gingival fibroblasts, and to provide oral agents with high safety having excellent type I collagen production promoting action in normal human gingival fibroblasts.SOLUTION: The present invention provides a type I collagen production promoter in normal human gingival fibroblasts containing at least one selected from the group consisting of dipotassium glycyrrhizinate, Lycium chinense Miller extract, Scutellaria baicalensis extract, Glycyrrhiza uralensis Fisch. extract, Lonicera japonica extract, Royal jelly extract, Guttiferae extract, Mulberry bark extract, and Rubus suavissimus S. Lee extract, and an oral agent containing the type I collagen production promoter in normal human gingival fibroblasts.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an agent for promoting type I collagen production in normal human gingival fibroblasts and an oral preparation. [Background technology]

[0002] Gums are one of the periodontal tissues that support the teeth, and surround the roots of the teeth. Gums are made up of two layers: epithelial tissue that is in contact with the outside world, and dermal tissue underneath the epithelial tissue. It is said that about 60% of the gingiva is collagen, which is responsible for the elasticity and adhesion of the gums.

[0003] Gingival fibroblasts are present in the dermis tissue, and are known to produce type I collagen. It is also known that the production of type I collagen in gingival fibroblasts decreases with age and due to toxins released by bacteria causing periodontal disease. Therefore, in order to improve the health of periodontal tissues, it is thought that promoting the production of type I collagen in gingival fibroblasts is necessary.

[0004] To date, compositions have been proposed for medicinal use to maintain and improve gums, including compositions that contain astaxanthin and / or fatty acid esters of astaxanthin as active ingredients and that suppress and prevent apoptosis of gingival cells (see, for example, Patent Document 1). However, the above proposal does not promote the production of type I collagen in gingival fibroblasts.

[0005] Therefore, there is currently a strong demand for the rapid development of a highly safe substance that has excellent type I collagen production promoting activity in normal human gingival fibroblasts. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] JP 2015-110526 A Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention aims to solve the above-mentioned conventional problems and achieve the following objectives: That is, the present invention aims to provide a type I collagen production promoter in normal human gingival fibroblasts that has an excellent type I collagen production promoting effect in normal human gingival fibroblasts and is highly safe. Another object of the present invention is to provide an oral preparation which has an excellent effect of promoting type I collagen production in normal human gingival fibroblasts and is highly safe. [Means for solving the problem]

[0008] As a result of intensive research conducted by the present inventors in order to solve the above-mentioned problems, it was found that at least one selected from the group consisting of dipotassium glycyrrhizinate, wolfberry extract, Scutellaria root extract, licorice extract, carrot extract, royal jelly extract, Hypericum perforatum extract, Sophora japonica extract and sweet tea extract has an excellent effect of promoting type I collagen production in normal human gingival fibroblasts, and the present invention was completed based on this finding.

[0009] The present invention is based on the above findings of the present inventor, and the means for solving the above problems are as follows. <1> This is a type I collagen production promoter in normal human gingival fibroblasts, characterized by containing at least one selected from the group consisting of dipotassium glycyrrhizinate, wolfberry extract, Scutellaria root extract, licorice extract, carrot extract, royal jelly extract, Hypericum perforatum extract, Sophora japonica extract, and sweet tea extract. <2> The above <1> The oral preparation is characterized by containing the promoter for type I collagen production in normal human gingival fibroblasts described in the above. Effect of the Invention

[0010] The type I collagen production promoter in normal human gingival fibroblasts of the present invention solves the above-mentioned conventional problems, and provides a type I collagen production promoter in normal human gingival fibroblasts that has excellent type I collagen production promoting effect in normal human gingival fibroblasts and is highly safe. The oral preparation of the present invention solves the above-mentioned conventional problems, and provides an oral preparation that has an excellent type I collagen production promoting effect in normal human gingival fibroblasts and is highly safe. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] (Promotes type I collagen production in normal human gingival fibroblasts) The type I collagen production promoter of the present invention in normal human gingival fibroblasts contains at least one selected from the group consisting of dipotassium glycyrrhizinate, wolfberry extract, Scutellaria root extract, licorice extract, carrot extract, royal jelly extract, Hypericum perforatum extract, Sophora japonica extract and sweet tea extract, and further contains other ingredients as necessary.

[0012] It was not previously known that dipotassium glycyrrhizinate, wolfberry extract, Scutellaria root extract, licorice extract, carrot extract, royal jelly extract, Hypericum perforatum extract, Sophora japonica extract and sweet tea extract have excellent type I collagen production promoting effects in normal human gingival fibroblasts and are useful as type I collagen production promoters in normal human gingival fibroblasts, and this is a new discovery by the present inventors.

[0013] The dipotassium glycyrrhizinate, wolfberry extract, Scutellaria root extract, licorice extract, carrot extract, royal jelly extract, Hypericum perforatum extract, Sophora japonica extract and sweet tea extract may be used alone or in combination of two or more.

[0014] <Dipotassium glycyrrhizinate> Dipotassium glycyrrhizinate is C 42 H 60 K2O16 It is a compound with a molecular weight of 899.1. Dipotassium glycyrrhizinate used may be prepared by chemical synthesis or may be a commercially available product. The method of chemical synthesis is not particularly limited and can be appropriately selected depending on the purpose. For example, there is a method of reacting glycyrrhizinic acid with potassium hydroxide (KOH) or the like.

[0015] The method for obtaining the glycyrrhizinic acid is not particularly limited and can be appropriately selected depending on the purpose. Examples include a method using a commercially available product, and a method for obtaining the glycyrrhizinic acid by at least one of isolation and purification from a plant extract containing glycyrrhizinic acid.

[0016] The plant extract containing glycyrrhizinic acid may be an extract obtained using a plant containing glycyrrhizinic acid as an extraction raw material, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, or a crude or purified product thereof. The plant extract containing glycyrrhizic acid can be obtained by a method generally used for extracting plants. An example of a plant containing glycyrrhizic acid is licorice.

[0017] <Wolfberry extract> Wolfberry (scientific name: Lycia in Chinese or Lycia barbarian ) is a plant belonging to the genus Lycium in the family Solanaceae, is widely distributed in East Asia, and can be easily obtained in these areas.

[0018] The wolfberry extract may be prepared from the part of the wolfberry used as the extraction raw material, or a commercially available product may be used. The part of the wolfberry to be extracted is not particularly limited and can be appropriately selected depending on the purpose, but the leaves are preferred. The method for preparing the wolfberry extract is not particularly limited and can be appropriately selected depending on the purpose. For example, the wolfberry extract can be prepared by the method for preparing extracts of natural products described below.

[0019] <Scutellaria root extract> Scutellaria (herbal medicine name) is a perennial plant belonging to the Scutellaria genus of the Lamiaceae family that is distributed in northern and northeastern China, Mongolia, etc. Skullcap Baikal Scutellaria Baicalensis is the root of Scutellaria Baicalensis, which is easily available in these areas. Scutellaria Baicalensis has traditionally been used as a stomachic, antiallergic, etc.

[0020] The Scutellaria root extract may be prepared from the roots of Scutellaria baicalensis or may be a commercially available product. The method for preparing the Scutellaria root extract is not particularly limited and may be appropriately selected depending on the purpose. For example, the extract may be prepared by a method for preparing extracts of natural products, which will be described later.

[0021] <Licorice extract> Licorice (Glycyrrhiza glabra) is a member of the legume family Glycyrrhiza Licorice Licorice is a perennial herb belonging to the genus Glycyrrhiza and has been used as a medicinal or sweetener ingredient since ancient times. Glycyrrhiza hairless ), Glycyrrhiza inflata ( Glycyrrhiza inflated ), Glycyrrhiza uralensis ( Glycyrrhiza Ural ), Glycyrrhiza aspera ( Glycyrrhiza rough ), Glycyrrhiza eurycarpa ( Glycyrrhiza Eurycarpa ), Glycyrrhiza pallidiflora ( Glycyrrhiza pale-flowered ), Glycyrrhiza yunnanensis ( Glycyrrhiza from Yunnan ), Glycyrrhiza lepidota ( Glycyrrhiza elegant ), Glycyrrhiza echinata ( Glycyrrhiza horsetail), Glycyrrhiza acanthocarpa ( Glycyrrhiza acanthocarpa ) and many other types.

[0022] The licorice extract may be prepared from the part of the plant used as the raw material for extraction, or a commercially available product may be used. The type of licorice used as the raw material for extraction is not particularly limited and can be appropriately selected depending on the purpose. The part of licorice to be extracted is not particularly limited and may be appropriately selected depending on the purpose, and examples thereof include leaves, branches, bark, trunks, stems, fruits, seeds, flowers and other above-ground parts, roots, rhizomes, and mixtures of these parts. Among these, roots, leaves, and rhizomes are preferred. The method for preparing the licorice extract is not particularly limited and can be appropriately selected depending on the purpose. For example, the licorice extract can be prepared by a method for preparing extracts of natural products, which will be described later.

[0023] <Honey extract> Ninja (scientific name: Honeysuckle Japanese ) is a plant belonging to the Caprifoliaceae family that grows in various parts of China, Korea, and Japan and can be easily obtained from these areas.

[0024] The above-mentioned ginseng extract may be prepared from the extraction part used as the extraction raw material, or a commercially available product may be used. The part of the plant from which the extract is made is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include flower buds, leaves, branches, seeds, bark, roots, stems, and mixtures of these parts. Among these, leaves and stems are preferred. The method for preparing the ginseng extract is not particularly limited and can be appropriately selected depending on the purpose. For example, the extract can be prepared by a method for preparing an extract of a natural product, which will be described later.

[0025] <Royal jelly extract> Royal jelly is produced by the European honeybee (scientific name: Apis moniliformes), which belongs to the genus Apis and family Apidae and is distributed in Europe, Africa, etc. Bee honey-bearing L., also known as Western honeybee) or Eastern honeybee (scientific name: Bee eleven It is a secretion from the pharyngeal glands of young worker bees (Radoszkowski) that is used to feed the future queen bees and the adult queen bees.

[0026] The royal jelly extract to be used may be one prepared from royal jelly, or a commercially available product may be used. The method for preparing the royal jelly extract is not particularly limited and can be appropriately selected depending on the purpose. For example, the royal jelly extract can be prepared by the method for preparing extracts of natural products described below.

[0027] <Hypericum extract> Hypericum ( Hypericum erect , Hypericum perforated ) is a perennial herb belonging to the genus Hypericum in the family Hypericaceae, which grows wild in Honshu, Shikoku, Kyushu, etc. and can be easily obtained from these areas.

[0028] The Hypericum extract may be prepared from the part of the plant used as the raw material for extraction, or a commercially available product may be used. The part of Hypericum to be extracted is not particularly limited and may be appropriately selected depending on the purpose, and examples thereof include leaves, stems, roots, flowers, above-ground parts, and mixtures of these parts. Among these, above-ground parts and the whole plant are preferred. The method for preparing the Hypericum extract is not particularly limited and can be appropriately selected depending on the purpose. For example, the extract can be prepared by a method for preparing an extract of a natural product, which will be described later.

[0029] <Moroccanus arbutus extract> Sohakuhi (herbal medicine name) is a deciduous tree found in China and other parts of the world that belongs to the genus Mulberry in the family Mulberry. Mulberry white The root bark of Morus albicans L. is easily available in these areas. Morus albicans has traditionally been used as an anti-inflammatory, diuretic, antipyretic, and analgesic drug.

[0030] The above-mentioned Morus alba extract may be prepared from the root bark of Morus alba or may be a commercially available product. The method for preparing the Morus albicans extract is not particularly limited and may be appropriately selected depending on the purpose. For example, the extract may be prepared by a method for preparing an extract of a natural product, which will be described later.

[0031] <Sweet tea extract> Sweet tea ( Blackberry most sweet Rubus fragilis is a shrub belonging to the genus Rubus in the family Rosaceae, and grows naturally in southern China, where it can be easily obtained. Tiancha extract has been used as an antiallergic agent.

[0032] The sweet tea extract may be prepared from the part of the tea plant used as the raw material for extraction, or a commercially available product may be used. The part of the sweet tea to be extracted is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include above-ground parts such as leaves, stems, flowers, and fruits, underground parts such as roots, and mixtures of these parts. Among these, leaves are preferred. The method for preparing the sweet tea extract is not particularly limited and can be appropriately selected depending on the purpose. For example, the extract can be prepared by a method for preparing an extract of a natural product, which will be described later.

[0033] -Method for preparing extracts from natural products- The above-mentioned wolfberry extract, Scutellaria root extract, licorice extract, honeysuckle extract, royal jelly extract, Hypericum extract, Sophora japonica extract and sweet tea extract (hereinafter sometimes referred to as "extracts of various natural products") can be easily obtained by utilizing a method generally used for plant extraction. The extracts of various natural products include extracts of various natural products, dilutions or concentrates of the extracts, dried products of the extracts, or crude or purified products thereof.

[0034] The method for preparing the extracts from the various natural products is not particularly limited and can be appropriately selected depending on the purpose. For example, the extract can be obtained by drying the raw material for extraction, and then subjecting it to extraction with an extraction solvent, either directly or after crushing using a crusher. The drying can be performed in the sun or using a commonly used dryer. In addition, the extract may be used after pretreatment such as degreasing with a non-polar solvent such as hexane. By carrying out pretreatment such as degreasing, extraction with a polar solvent can be carried out efficiently.

[0035] The extraction solvent is not particularly limited and can be appropriately selected depending on the purpose. Examples of the extraction solvent include water, a hydrophilic organic solvent, and a mixture thereof.

[0036] The water that can be used as the extraction solvent is not particularly limited and can be appropriately selected depending on the purpose, and includes, for example, pure water, tap water, well water, mineral water, hot spring water, spring water, fresh water, etc., as well as water that has been subjected to various treatments. Examples of treatments that can be applied to water include purification, heating, sterilization, filtration, ion exchange, adjustment of osmotic pressure, buffering, etc. Therefore, water that can be used as the extraction solvent also includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered physiological saline, etc.

[0037] The hydrophilic organic solvent that can be used as the extraction solvent for the plant is not particularly limited and can be appropriately selected depending on the purpose. Examples of the hydrophilic organic solvent include lower alcohols having 1 to 5 carbon atoms, such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones, such as acetone and methyl ethyl ketone; and polyhydric alcohols having 2 to 5 carbon atoms, such as 1,3-butylene glycol, propylene glycol, and glycerin. Mixtures of these hydrophilic organic solvents with water can also be used.

[0038] When using a mixed solvent of water and the hydrophilic organic solvent, the mixing ratio is not particularly limited and can be appropriately selected depending on the purpose. For example, in the case of a mixed solvent of water and a lower alcohol, the mixing ratio of water to the lower alcohol is preferably 9:1 to 1:9 (volume ratio), more preferably 8:2 to 2:8 (volume ratio). In addition, in the case of a mixed solvent of water and a lower aliphatic ketone, the mixing ratio of water to the lower aliphatic ketone is preferably 9:1 to 2:8 (volume ratio). In addition, in the case of a mixed solvent of water and a polyhydric alcohol, the mixing ratio of water to the polyhydric alcohol is preferably 5:5 to 1:9 (volume ratio).

[0039] The extraction solvent is preferably used at room temperature or at a temperature below the boiling point of the solvent.

[0040] The extraction method is not particularly limited and can be appropriately selected depending on the purpose. For example, the extraction raw material is immersed in an extraction solvent having an amount (mass ratio) of 5 to 15 times the amount of the extraction raw material, and soluble components are extracted at room temperature or under reflux heating, and then the extraction residue is removed by filtration to obtain an extract. Next, the solvent is distilled off from the extract to obtain a paste-like concentrate, and this concentrate is further dried to obtain a dried product. The conditions for the extraction are not particularly limited and can be appropriately selected depending on the purpose.

[0041] In addition, the obtained extracts of the various natural products may be subjected to treatments such as dilution, concentration, drying, purification, etc. according to conventional methods in order to obtain diluted products, concentrates, dried products, crude products, purified products, etc. of the extracts of the various natural products. The above-obtained extracts of various natural products can be used as they are as promoters of type I collagen production in normal human gingival fibroblasts, but the above-mentioned concentrated solutions and dried products are preferred in terms of ease of use. In obtaining the dried products, carriers such as dextrin and cyclodextrin may be added to improve hygroscopicity.

[0042] The content of at least one type of type I collagen production promoter in normal human gingival fibroblasts selected from the group consisting of dipotassium glycyrrhizinate, wolfberry extract, Scutellaria root extract, licorice extract, carrot extract, royal jelly extract, Hypericum perforatum extract, Sophora japonica extract, and sweet tea extract is not particularly limited and can be appropriately selected depending on the purpose.

[0043] <Other ingredients> The other components are not particularly limited and can be appropriately selected depending on the purpose. Examples of the other components include excipients, moisture-proofing agents, preservatives, strengthening agents, thickeners, emulsifiers, antioxidants, sweeteners, acidulants, seasonings, colorants, fragrances, whitening agents, moisturizers, oily components, UV absorbers, surfactants, alcohols, powder components, colorants, aqueous components, water, and skin nutrients. The content of the other components in the promoter for type I collagen production in normal human gingival fibroblasts is not particularly limited and can be appropriately selected depending on the purpose.

[0044] The above dipotassium glycyrrhizinate, wolfberry extract, Scutellaria root extract, licorice extract, carrot extract, royal jelly extract, Hypericum perforatum extract, Sophora japonica extract and sweet tea extract have excellent type I collagen production promoting effects in normal human gingival fibroblasts, and therefore can be used as active ingredients of type I collagen production promoters in normal human gingival fibroblasts.

[0045] <Application> The use of the type I collagen production promoter in normal human gingival fibroblasts of the present invention is not particularly limited and can be appropriately selected depending on the purpose. For example, it can be suitably used as an oral preparation as described below, and its content, method of use and dosage form can be appropriately selected depending on the purpose of use.

[0046] (Oral preparations) The oral preparation of the present invention contains the promoter of type I collagen production in normal human gingival fibroblasts of the present invention, and further contains other ingredients as required.

[0047] The content of the promoter for type I collagen production in normal human gingival fibroblasts in the oral preparation is not particularly limited and can be appropriately selected depending on the purpose. The oral preparation may consist only of the promoter for type I collagen production in normal human gingival fibroblasts.

[0048] The other components in the oral preparation are not particularly limited and can be appropriately selected depending on the purpose. For example, main components, auxiliary components or other components used in the production of ordinary oral preparations can be used in combination. More specific examples include abrasives such as calcium hydrogen phosphate, calcium carbonate, insoluble sodium metaphosphate, aluminosilicate, anhydrous silicic acid, and resin; surfactants such as long-chain sodium alkyl sulfate, sodium lauryl sulfoacetate, lauryl diethanolamide, and sucrose fatty acid esters; binders such as carboxymethylcellulose (CMC), hydroxyethylcellulose, alginates, carrageenan, gum arabic, and polyvinyl alcohol; thickeners such as polyethylene glycol, sorbitol, glycerin, and propylene glycol; sweeteners such as saccharin, steviosides, glycyrrhizic acid, and thaumatin; preservatives such as dehydroacetic acid and sodium dehydroacetate; fragrances such as menthol, carvone, eugenol, anethole, peppermint oil, spearmint oil, peppermint oil, eucalyptus oil, ginger oil, and anise oil; and various pigments. These may be used alone or in combination of two or more. The contents of other ingredients in the oral preparation are not particularly limited and may be appropriately selected depending on the purpose.

[0049] Since the oral preparation of the present invention has excellent type I collagen production promoting properties in normal human gingival fibroblasts, it can be suitably used, for example, for promoting collagen regeneration in periodontal tissues.

[0050] The form of the oral preparation is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include toothpaste, mouthwash, lozenges, gum massage cream, gargle, and mouth freshener.

[0051] The type I collagen production promoter in normal human gingival fibroblasts and the oral preparation of the present invention are preferably applied to humans, but can also be applied to animals other than humans as long as their respective functional effects are achieved. EXAMPLES

[0052] Hereinafter, manufacturing examples and test examples of the present invention will be described, but the present invention is not limited to these manufacturing examples and test examples.

[0053] The materials used in Test Examples 1-1 and 1-2 described below are as follows. (1) Dipotassium glycyrrhizinate (external glycyrrhizinate dipotassium, manufactured by Maruzen Pharmaceutical Co., Ltd.) (2) Scutellaria root extract (Scutellaria root extract BG-LC (extraction raw material: Scutellaria root (root), extraction solvent: 50% by volume 1,3-butylene glycol), manufactured by Maruzen Pharmaceutical Co., Ltd.) (3) Licorice extract (Licorice extract (extraction raw material: licorice (root), extraction solvent: water), manufactured by Maruzen Pharmaceutical Co., Ltd.) (4) Panax ginseng extract (Panax ginseng extract-J (extraction raw material: Panax ginseng (leaves), extraction solvent: 90% ethanol by volume), manufactured by Maruzen Pharmaceutical Co., Ltd.) (5) Royal jelly extract (Royal jelly extract BG (extraction solvent: 50% by volume 1,3-butylene glycol), manufactured by Maruzen Pharmaceutical Co., Ltd.) (6) Hypericum extract (Hypericum extract-J (extraction raw material: Hypericum perforatum (flowers, leaves and stems), extraction solvent: 90% by volume ethanol), manufactured by Maruzen Pharmaceutical Co., Ltd.) (7) Sophora umbellata extract (Sophora umbellata extract BG (extraction raw material: mulberry (root bark), extraction solvent: 50% by volume 1,3-butylene glycol), manufactured by Maruzen Pharmaceutical Co., Ltd.) (8) Sweet tea extract (Tencha extract BGW (extraction raw material: sweet tea (leaves), extraction solvent: 50% by volume 1,3-butylene glycol), manufactured by Maruzen Pharmaceutical Co., Ltd.) (9) Wolfberry extract (see Preparation Examples 1 to 3 below)

[0054] (Production Examples 1 to 3) -Manufacturing of wolfberry extract- 20 g of dried wolfberry leaves were added with 10 times the amount of solvent (see Table 1 below) and refluxed for 2 hours. After filtration under reduced pressure, the solvent was removed to obtain each extract. The yields are also shown in Table 1.

[0055]

Table 1

[0056] (Test Example 1-1) <Test for promoting the production of type I collagen in NHGF cells> Using each of the above-mentioned materials as a test sample, the promoting effect on the production of type I collagen in NHGF cells was tested by the following test method.

[0057] Normal Human Gingival Fibroblasts were cultured using low-serum medium for normal human fibroblast proliferation (LFK-LS1038), and then the cells were collected by trypsin treatment. The collected cells were diluted with LFK-LS1038 medium to a concentration of 1.6×10 5 cells / mL, and then seeded at 100 μL per well in a 96-well plate and cultured for 1 day. After the culture was completed, 100 μL of the test sample dissolved in serum-free medium for normal human fibroblast proliferation (LFK-LS1010) (see Tables 2-1 and 2-2 below for the sample concentration) was added to each well and cultured for 3 days. As a control, the same culture was performed using LFK-LS1010 medium without the sample. After the culture was completed, the amount of type I collagen in the medium of each well was measured by the ELISA method. From the measurement results, the promotion rate of type I collagen production (%) was calculated by the following formula 1. The results are shown in the upper rows of Tables 2-1 and 2-2. <Formula 1> Promotion rate of type I collagen production (%) = A / B × 100 In formula 1, "A" represents "the amount of type I collagen when the test sample is added", and "B" represents "the amount of type I collagen when the sample is not added".

[0058] (Test Example 1-2) <Test for promoting the production of type I collagen in NB1RGB cells> Using each of the above-mentioned materials as a test sample, the promoting effect on the production of type I collagen in NB1RGB cells was tested by the following test method.

[0059] Normal human skin fibroblasts (NB1RGB cells) were cultured in Dulbecco's MEM medium containing 10% FBS, and then the cells were harvested by trypsinization. The harvested cells were collected at a concentration of 1.6 × 10 5 After diluting with the above medium to a concentration of cells / mL, 100 μL was seeded per well of a 96-well plate and cultured overnight. After the culture was completed, the medium was removed, and 150 μL of the test sample dissolved in 0.25% FBS-containing Dulbecco's MEM medium (see Tables 2-1 and 2-2 below for sample concentration) was added to each well and cultured for 3 days. As a control, culture was performed in the same manner using 0.25% FBS-containing Dulbecco's MEM medium without the addition of sample. After the culture was completed, the amount of type I collagen in the medium of each well was measured by ELISA. From the measurement results, the type I collagen production promotion rate (%) was calculated using the following formula 2. The results are shown in the lower part of Tables 2-1 and 2-2. <Expression 2> Type I collagen production promotion rate (%) = C / D x 100 In formula 2, "C" represents the "amount of type I collagen when a test sample is added," and "D" represents the "amount of type I collagen when no sample is added."

[0060] [Table 2-1]

[0061] [Table 2-2]

[0062] The results in Tables 2-1 and 2-2 show that in normal human skin fibroblasts, the rate of promotion of type I collagen production was at most about 114%. On the other hand, when the same type and concentration of material was used, the rate of type I collagen production promotion in normal human gingival fibroblasts was at least higher than the rate of type I collagen production promotion in normal human skin fibroblasts. Therefore, it was confirmed that dipotassium glycyrrhizinate, wolfberry extract, Scutellaria root extract, licorice extract, honeysuckle extract, royal jelly extract, Hypericum perforatum extract, Sophora japonica extract and sweet tea extract exhibit excellent type I collagen production promoting effects specifically in normal human gingival fibroblasts, and these materials are considered to be excellent type I collagen production promoters in normal human gingival fibroblasts and active ingredients for oral preparations.

[0063] (Combination example 1) A mouthwash having the following composition was prepared by a conventional method. Dipotassium glycyrrhizinate 0.2 parts by mass (External spec dipotassium glycyrrhizinate, manufactured by Maruzen Pharmaceutical Co., Ltd.) Dicalcium phosphate 45.0 parts by mass Sodium carboxymethylcellulose 1.0 part by weight Glycerin 20.0 parts by weight Sodium lauryl sulfate 2.0 parts by weight · Flavoring 1.0 parts by mass · Purified water 30.0 parts by mass

[0064] (Combination example 2) A mouthwash having the following composition was prepared by a conventional method. Scutellaria root extract 0.2 parts by weight (Scutellaria root extract BG-LC, manufactured by Maruzen Pharmaceutical Co., Ltd.) Dicalcium phosphate 45.0 parts by mass Sodium carboxymethylcellulose 1.0 part by weight Glycerin 20.0 parts by weight Sodium lauryl sulfate 2.0 parts by weight · Flavoring 1.0 parts by mass · Purified water 30.0 parts by mass

[0065] (Combination example 3) A mouthwash having the following composition was prepared by a conventional method. Licorice extract 0.2 parts by weight (Licorice extract, manufactured by Maruzen Pharmaceutical Co., Ltd.) Dicalcium phosphate 45.0 parts by mass Sodium carboxymethylcellulose 1.0 part by weight Glycerin 20.0 parts by weight Sodium lauryl sulfate 2.0 parts by weight · Flavoring 1.0 parts by mass · Purified water 30.0 parts by mass

[0066] (Combination example 4) A mouthwash having the following composition was prepared by a conventional method. · Ninja extract 0.2 parts by mass (Nindou Extract-J, manufactured by Maruzen Pharmaceutical Co., Ltd.) Dicalcium phosphate 45.0 parts by mass Sodium carboxymethylcellulose 1.0 part by weight Glycerin 20.0 parts by weight Sodium lauryl sulfate 2.0 parts by weight · Flavoring 1.0 parts by mass · Purified water 30.0 parts by mass

[0067] (Combination example 5) A toothpaste having the following composition was prepared in a conventional manner. Royal jelly extract 0.1 parts by weight (Royal jelly extract BG, manufactured by Maruzen Pharmaceutical Co., Ltd.) Calcium carbonate 39.0 parts by mass Sorbitol 22.0 parts by weight Carboxymethyl cellulose 1.1 parts by weight Sodium lauryl sulfate 1.3 parts by weight Saccharin 0.1 parts by weight · Flavoring 1.0 parts by mass Chlorhexidine hydrochloride 0.01 parts by weight · Purified water 35.0 parts by mass

[0068] (Combination example 6) A toothpaste having the following composition was prepared in a conventional manner. Hypericum extract 0.1 parts by weight (Hypericum extract-J, manufactured by Maruzen Pharmaceutical Co., Ltd.) Calcium carbonate 39.0 parts by mass Sorbitol 22.0 parts by weight Carboxymethyl cellulose 1.1 parts by weight Sodium lauryl sulfate 1.3 parts by weight Saccharin 0.1 parts by weight · Flavoring 1.0 parts by mass Chlorhexidine hydrochloride 0.01 parts by weight · Purified water 35.0 parts by mass

[0069] (Combination example 7) A toothpaste having the following composition was prepared in a conventional manner. 0.1 parts by weight of Morus alba extract (Moroccanus sieboldii extract BG, manufactured by Maruzen Pharmaceutical Co., Ltd.) Calcium carbonate 39.0 parts by mass Sorbitol 22.0 parts by weight Carboxymethyl cellulose 1.1 parts by weight Sodium lauryl sulfate 1.3 parts by weight Saccharin 0.1 parts by weight · Flavoring 1.0 parts by mass Chlorhexidine hydrochloride 0.01 parts by weight · Purified water 35.0 parts by mass

[0070] (Combination example 8) A toothpaste having the following composition was prepared in a conventional manner. · Sweet tea extract 0.1 part by mass (Tencha extract BGW, manufactured by Maruzen Pharmaceutical Co., Ltd.) Calcium carbonate 39.0 parts by mass Sorbitol 22.0 parts by weight Carboxymethyl cellulose 1.1 parts by weight Sodium lauryl sulfate 1.3 parts by weight Saccharin 0.1 parts by weight · Flavoring 1.0 parts by mass Chlorhexidine hydrochloride 0.01 parts by weight · Purified water 35.0 parts by mass

[0071] (Combination example 9) A mouthwash having the following composition was prepared by a conventional method. Wolfberry extract 0.2 parts by weight (Hot water extract of wolfberry leaves of Production Example 1) Dicalcium phosphate 45.0 parts by mass Sodium carboxymethylcellulose 1.0 part by weight Glycerin 20.0 parts by weight Sodium lauryl sulfate 2.0 parts by weight · Flavoring 1.0 parts by mass · Purified water 30.0 parts by mass

[0072] (Combination example 10) A toothpaste having the following composition was prepared in a conventional manner. Wolfberry extract 0.1 parts by weight (50% by volume ethanol extract of wolfberry leaves, Production Example 2) Calcium carbonate 39.0 parts by mass Sorbitol 22.0 parts by weight Carboxymethyl cellulose 1.1 parts by weight Sodium lauryl sulfate 1.3 parts by weight Saccharin 0.1 parts by weight · Flavoring 1.0 parts by mass Chlorhexidine hydrochloride 0.01 parts by weight · Purified water 35.0 parts by mass

[0073] (Combination example 11) A toothpaste having the following composition was prepared in a conventional manner. Wolfberry extract 0.1 parts by weight (80% by volume ethanol extract of wolfberry leaves, Production Example 3) Calcium carbonate 39.0 parts by mass Sorbitol 22.0 parts by weight Carboxymethyl cellulose 1.1 parts by weight Sodium lauryl sulfate 1.3 parts by weight Saccharin 0.1 parts by weight · Flavoring 1.0 parts by mass Chlorhexidine hydrochloride 0.01 parts by weight · Purified water 35.0 parts by mass

Claims

1. A promoter for type I collagen production in normal human gingival fibroblasts, comprising an extract of Panax ginseng.

2. An oral preparation used to promote type I collagen production in normal human gingival fibroblasts, comprising:

2. An oral preparation comprising the promoter for type I collagen production in normal human gingival fibroblasts according to claim 1.

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