JP5921872B2 - Oral composition - Google Patents

Description

  An object of the present invention is to provide a novel periodontal disease inhibitor, a Candida inhibitor, and an oral composition.

  In the human oral cavity, extremely many types of bacteria exceeding 500 to 700 species have been found, and an aggregate, that is, a bacterial flora is constantly formed on the mucosal surface. This intraoral flora is maintained in balance by complex interactions, and has a function of preventing invasion, that is, imparting resistance by antagonizing foreign bacteria. However, although it causes oral infection, periodontal disease is said to be the infection with the highest number of infections.

  Periodontal diseases that develop due to infection with periodontal disease bacteria are roughly classified into gingivitis, periodontitis, and occlusal trauma. Recently, it is known that periodontal disease becomes chronic and causes infections such as respiratory diseases, heart diseases, diabetes, and premature birth due to periodontal disease bacteria. As an antibacterial agent against such periodontal disease bacteria, an agent containing cocoa contained in cacao mass as an active ingredient is known (Patent Document 1).

  The main cause of periodontal disease is bacteria in the plaque that accumulate in the periodontal pocket. Usually, Gram-positive bacteria occupy most of the periodontal pockets of healthy individuals, but as periodontal disease progresses, Porphylomonas gingivalis, Fusobacterium nucleatum, and Aggregate Gram-negative bacteria such as Aggregatibacter actinomycetemcomitans increase. Moreover, Prevotera intermedia is well known as a periodontal disease bacterium that develops female hormones such as estradiol and progesterone.

  In addition, with the recent increase in the number of elderly people, prevention of oral infections and improvement of oral hygiene among elderly people are extremely important issues. In particular, it is known that elderly people who need care, etc., cause opportunistic infections when the proportion of opportunistic bacteria such as Candida albicans detected in the oral cavity is increased compared to independent elderly people. It is known to use xylitol as a denture stabilizer for the prevention of such Candida (Patent Document 2).

  However, with regard to the prevention of periodontal disease or Candida, a number of studies have been conducted so far, and toothpastes and enamels containing antibacterial substances effective against these bacteria have been developed. However, there are few safe and effective ones, and prevention of oral diseases has become an important issue as aging progresses in the future.

International Publication No. 2003/99304 Pamphlet Japanese Patent Laid-Open No. 2000-333973

  Accordingly, an object of the present invention is to provide a novel and useful periodontal disease inhibitor, candida inhibitor, and oral composition.

  Based on the above findings, the present inventors have conducted extensive research and investigations to solve the above problems, and as a result, the present inventors have found that neem extract, datura extract, rita extract, and proteoglycan are teeth. It has been found that it has an effect of suppressing peripathogenic fungi, and in the neem extract and Rita extract, it has been found to have an effect of further suppressing Candida, and the present invention has been completed.

  ADVANTAGE OF THE INVENTION According to this invention, periodontal disease bacteria or Candida bacteria can be suppressed and an effective composition for oral cavity can be provided.

It is a figure which shows the effect | action which suppresses various periodontal disease bacteria (Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphylomonas gingivalis, Prevotera intermedia) and Candida albicans of the neem extract of this invention. It is a figure which shows the effect | action which suppresses various periodontal disease bacteria (Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphylomonas gingivalis, Prevotera intermedia), Candida albicans of the Kempo thistle extract of this invention. It is a figure which shows the effect | action which suppresses various periodontal bacteria (Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphylomonas gingivalis, Prevotera intermedia) and Candida albicans of the Rita extract of this invention. It is a figure which shows the effect | action which suppresses various periodontal disease bacteria (Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphylomonas gingivalis, Prevotera intermedia), Candida albicans of the proteoglycan of this invention.

  As used herein, the term “Indian Sendan” refers to the plant of the family Meliaceae, Azadirachta: Azadirachta indica, flower, ear, pericarp, fruit, false fruit, stem, leaf, Branches, branches and leaves, bark, rhizome, root bark, roots, seeds, aerial parts or whole plants are used.

  As used in the present invention, the “Chrysanthemum” is a plant belonging to the family Compositae or Cynara: Cynara scolymus, flower, ear, skin, fruit, fruit, stem, leaf, branch Branches, leaves, stems, bark, rhizomes, root barks, roots, seeds, aerial parts or whole plants are used.

  “Rita” used in the present invention is a plant belonging to the family Sapindaceae and Sapindus: flowers of Rita (Sapindus Trifoliatus), flower ears, pericarps, fruits, false fruits, stems, leaves, branches, branches and leaves, Use stem, bark, rhizome, root bark, root, seed, above-ground part or whole plant.

  The “Proteoglycan” used in the present invention is an extract of a complex of mucopolysaccharide and protein, and is a kind of glycoprotein. A mucopolysaccharide and protein complex has a molecular structure of about 1 to 10 million molecular weight, in which several to several tens of mucopolysaccharide chains are bound to the polypeptide chain of the protein and contain 5 to 50% protein. The acidic mucopolysaccharide-protein complex. Constituent acidic mucopolysaccharides mainly include hyaluronic acid, chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, chondroitin 6,9-sulfate, chondroitin, heparin, heparitin sulfate, keratosulfate and the like. This proteoglycan extract is present in animal (mammals: cattle, etc., fish: salmon, etc.) tissues, mainly in the extracellular matrix and cell surface, and fills the space between many tissues. Extracted from bone fluid that smoothes cement, cartilage, tendons, skin, and joints.

  Examples of the extraction solvent for obtaining each plant extract used in the present invention include water, lower alcohols such as methanol, ethanol, propyl alcohol, isopropyl alcohol, butanol and isobutanol, or hydrous lower alcohols, propylene glycol, 1,3. -Butylene glycol, 1,2-butylene glycol, 1,4-butylene glycol, 1,5-pentanediol, 1,2-pentanediol, 1,3-pentanediol, 1,4-pentanediol, 1,3, Polyhydric alcohol such as 5-pentanetriol, glycerin, polyethylene glycol (molecular weight 100 to 100,000) or hydrous polyhydric alcohol, acetone, ethyl acetate, diethyl ether, dimethyl ether, ethyl methyl ether, dioxane, acetonitrile, xylene, benzene, chloroform , Carbon tetrachloride, phenol, torr In various organic solvents, such as acids (hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, formic acid, acetic acid, etc.) and alkalis (sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonia, etc.) 1 type or 2 types or more of mixed liquids are mentioned, It is preferable to select 1 type, or 2 or more types especially chosen from water, ethanol, and 1, 3- butylene glycol. However, if it is not preferable to use a solvent depending on the application, use only water, or perform extraction with a highly volatile solvent that can be easily removed after extraction, and dissolve in water after removing the solvent. Such a method is also possible.

  Regarding the extraction method, the temperature of the solvent, the weight ratio of the solvent to the raw material, or the extraction time can be arbitrarily set for various raw materials and the solvent used. Although it can set arbitrarily as the temperature of a solvent in the range of -4 degreeC to 100 degreeC, 10-40 degreeC vicinity is preferable from the point of stability of the component contained in a raw material. Also, the weight ratio of the solvent to the raw material can be arbitrarily set, for example, in the range of the raw material: solvent 4: 1 to 1: 100, and the weight ratio of 1: 1 to 1:20 is particularly preferable.

  Each plant extract used in the present invention can be further subjected to a refining operation after solvent extraction. The refining operation includes an acid (hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, organic acid, etc.) or an alkali (water). Decomposition by adding sodium oxide, calcium hydroxide, ammonia, etc., fermentation or metabolic conversion by microorganisms, component adsorption by ion exchange resin, activated carbon, diatomaceous earth, etc., various separation modes (ion exchange, hydrophilic adsorption, hydrophobic adsorption) Fractionation using chromatography with size exclusion, ligand exchange, affinity, etc.), filtration using filter paper, membrane filter, ultrafiltration membrane, etc., pressurization or decompression, heating or cooling, drying, pH Examples include adjustment, deodorization, decolorization, and long-term stationary storage, and it is possible to arbitrarily select and combine them. The shape of each plant extract may be any shape such as liquid, solid, powder, and paste, and an optimum shape can be arbitrarily selected for carrying out the present invention.

  Periodontal disease bacteria inhibitor of the present invention, Candida fungus inhibitor, indendant extract, datura extract, Rita extract, proteoglycan content in the oral composition is not particularly limited as long as the effect can be confirmed. Generally, it is set within the range of 0.01 mg / g to 200 mg / g (the denominator indicates the weight of the preparation). The range of 0.1 mg / g to 20 mg / g is preferable.

  The shape of the periodontal disease inhibitor, candida inhibitor, and oral composition of the present invention may be any shape such as liquid, solid, powder, paste, etc., and is the optimal shape for carrying out the present invention. Can be arbitrarily selected.

  The composition for oral cavity of the present invention is prepared in various forms such as toothpaste, toothpaste, toothpaste such as liquid toothpaste, mouthwash, mouth freshener, gargle tablet, denture cleaner, troche, chewing gum and the like. Each composition can be prepared by an ordinary method according to the characteristics, using other optional components in addition to the above essential components within a range not impairing the effects of the present invention.

  It should be noted that the periodontal disease bacteria inhibitor, Candida bacteria inhibitor, and oral composition of the present invention may be arbitrarily selected and used in combination with the components and additives exemplified below within a range not impairing the effects of the present invention. It can be manufactured and can be added with more functionality. The content in the preparation is not particularly limited, but a concentration range of usually 0.0001 to 50% is preferable.

  As abrasives, for example, silica-based abrasives such as silicic anhydride, aluminum hydroxide, aluminum oxide, aluminosilicate, dicalcium phosphate, insoluble sodium metaphosphate, insoluble potassium metaphosphate, titanium oxide, synthetic resin, etc. as required Preferably used. These abrasives may be used alone or in combination of two or more (the amount is usually 3 to 90% of the total composition).

  Examples of the surfactant include water-soluble salts of higher alkyl sulfates having 8 to 18 carbon atoms in the alkyl group such as sodium lauryl sulfate and sodium myristyl sulfate, fatty acid groups such as sodium lauryl monoglyceride sulfonate and sodium coconut monoglyceride sulfonate. A water-soluble salt of higher fatty acid monoglyceride sulfonic acid having 10 to 18 carbon atoms, olefin sulfonic acid, paraffin sulfonic acid, other anionic active agents, stearyl monoglyceride, sucrose mono and dilaurate, and the like. 12-18 sucrose fatty acid ester, lactose fatty acid ester, lactitol fatty acid ester, maltitol fatty acid ester, stearic acid monoglyceride, polyoxyethylene sorbitan monolaurate Nonionic active agents such as polyoxyethylene hydrogenated castor oil, sorbitan monostearate condensate added with about 60 mol of ethylene glycol, a polymer of ethylene oxide and propylene oxide, and a derivative such as polyoxyethylene polyoxypropylene monolauryl ester, A surfactant such as an amphoteric active agent such as a betaine type or an amino acid type is used (usually 0.01 to 7% of the total composition).

  Examples of binders include carrageenan, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, cellulose derivatives such as sodium carboxymethylhydroxyethylcellulose, alkali metal alginates such as sodium alginate, propylene glycol alginate, xanthan gum, tragacanth gum, caraya gum, arabic 1 such as gums such as gums, synthetic binders such as polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, polyvinylpyrrolidone, gelling silica, gelling aluminum silica, bee gum, laponite, etc. More than one species can be blended (blend is usually 0.5-10% of the total composition).

  As the thickener, one or more of sorbit, glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, xylit, maltite, lactit and the like can be blended (blending amount is usually 1 to 50) %).

  Sweeteners such as saccharin sodium, stepioside, xylitol, neohesperidyl dihydrochalcone, glycyrrhizin, perilartine, thaumatin, aspartylphenylalanine methyl ester, p-methoxycinnamic aldehyde, sodium cyclamate, etc., p-hydroxymethylbenzoic acid as preservative , P-hydroxyethyl benzoic acid, p-hydroxypropyl benzoic acid, p-hydroxybutyl benzoic acid, sodium benzoate, lower fatty acid monoglyceride, etc. Wintergreen oil, spearmint oil, peppermint oil, sassafras oil, clove Oil, eucalyptus oil, etc. may be blended.

    Gelatin, peptone, albumin, brightener, silicone, pigment, and other components can be blended. Furthermore, fluorides such as sodium fluoride, sodium monofluorophosphate, tin fluoride, epsilon aminocaproic acid, tranexamic acid, dextranase, protease, mutanase, lysozyme, lytic enzyme, lytechenzyme, chlorhexidine salts, One or more active ingredients such as dihydrocholesterol, glycyrrhetin salts, glycyrrhetinic acid, caropeptides, vitamins, antibacterial agents, hyposensitivity agents such as potassium nitrate, and the like can be blended.

  The pH of the composition for oral cavity of the present invention is not particularly limited as long as it is in a range that does not cause safety problems in the oral cavity and the human body, but is preferably pH 6-9, more preferably 7-9. is there. If necessary, acetic acid, hydrochloric acid, sulfuric acid, nitric acid, citric acid, phosphoric acid, sodium hydroxide, potassium hydroxide, sodium acetate, sodium carbonate, sodium citrate, sodium hydrogen citrate, phosphorus An appropriate amount of sodium acid sodium, sodium hydrogen phosphate, or the like can be blended.

  Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

[Production Example 1]
100 g of neem leaves are crushed and added to 1 L of 50% 1,3-butylene glycol solution, soaked and extracted at room temperature to warm, then filtered using filter paper, dried, and neem extract About 7g was obtained.

[Production Example 2]
100 g of thistle thistle is pulverized, added to 1 L of 50% 1,3-butylene glycol solution, soaked and extracted at room temperature to warm, then filtered using filter paper, dried, and dried thistle extract About 10g was obtained.

[Production Example 3]
100g of Rita fruit is crushed, added to 1L of 50% 1,3-butylene glycol solution, soaked and extracted at room temperature to warm, then filtered using filter paper, dried, and about 9g of Rita extract Obtained.

[Production Example 4]
Nasal cartilage was collected from sputum, washed with physiological saline, and then pulverized to obtain salmon nasal cartilage mince. This minced 4% acetic acid is soaked at 4 ° C. for 48 hours and stirred to elute the crude proteoglycan. The eluate is filtered to remove insolubles, and then centrifuged and concentrated semi-solid proteoglycan is added. After being obtained, it was again immersed in 4% acetic acid to dissolve, and the resulting solution was sufficiently dialyzed to obtain a liquid proteoglycan having a high purity.

(Test 1) Inhibition test of periodontal disease bacteria and Candida bacteria "Test method and evaluation method"
Each sample is added to basal medium (Brain Heart Infusion broth (BD), supplemented hemin and menadione) to prepare a dilution series. Dispense 150 μl of each prepared medium into a well of a 96-well plate. Inoculate 10 μl each of the pre-cultured culture solution. (Inoculum number: P.gingivalis, P.intermedia, Aa is 1 × 10 ⁷ cells, F.nucleatum is 3 × 10 ⁶ cells, C.albicans is 0.5 × 10 ⁵ cells), then 37 ° C., 48 hours, Culture under aerobic (C. albicans) or anaerobic (other) conditions. The turbidity of each well was measured at 595 nm, and the results are shown in FIGS. In addition, it shows that antimicrobial power is so high that the numerical value of turbidity is low.
"Test strain"
Aggregatibacter actinomycetemcomitans Y4 strain (hereinafter abbreviated as Aa), Fusobacterium nucleatum ATCC25586 strain (hereinafter abbreviated as F. nucleatum), Porphyromonas gingivalis ATCC33277 strain (hereinafter abbreviated as P. gingivalis), Prevotella intermedia ATCC25611 strain Candida albicans ATCC18804 strain (hereinafter abbreviated as C. albicans) was used as a Candida bacterium.
"sample"
Samples include the neem extract, the thistle extract, the rita extract, and the proteoglycan of Production Examples 1 to 4 of the present invention at various concentrations (0.001 mg / ml, 00.1 mg / ml, 0.1 mg / ml, 1 mg / ml, 10 mg / ml) and added to the test.

(Test results)
The results are as shown in FIGS. 1 to 4, wherein the neem extract and Rita extract of the present invention have an inhibitory action on three types of periodontal fungi (F. nucleatum, P. gingivalis, P. intermedia). Was confirmed. In addition, it has been confirmed that the extract of thistle thistle has an inhibitory effect on all four types of periodontal disease bacteria (F. nucleatum, P. gingivalis, P. intermedia, Aa). Moreover, it was confirmed that the proteoglycan of the present invention has an action of slightly inhibiting one species (P. gingivalis) among periodontal disease bacteria. Furthermore, it was confirmed that the neem extract and the Rita extract of the present invention have an action of suppressing C. albicans.

(Prescription example) Manufacture of composition for oral cavity The preparation of various dosage forms by this invention was manufactured. The prescription example is shown below, but each prescription example may be produced by a conventional method in the production of each product, and only the blending amount is shown. The present invention is not limited to these.

(Formulation Example 1) Toothpaste
weight%
1.Dicalcium phosphate 40.0
2.Glycerin 20.0
3. Carrageenan 1.0
4.Sodium lauryl sulfate 1.5
5.Saccharin 0.2
6. Neem extract of Production Example 1 1.0
7. Chlorhexidine digluconate 0.1
8. Preservative (butyl paraoxybenzoate) appropriate amount
9. Fragrance (Apple water)
10.Coloring agent appropriate amount
11. Residue with 100 purified water

(Prescription Example 2) Toothpaste
weight%
1.Dicalcium phosphate 30.0
2.Glycerin 20.0
3.Cetylpyridinium chloride 0.2
4.Sodium lauryl sulfate 1.5
5.Saccharin sodium 0.1
6. Korean thistle extract of Production Example 2 2.0
7. Sodium monofluorophosphate 4.0
8. Preservative (methylparaben) appropriate amount
9. Fragrance (Peppermint water)
10.Coloring agent appropriate amount
11. Residue with 100 purified water

(Prescription Example 3) Toothpaste
weight%
1. Silicic anhydride 20.0
2.Sorbit liquid 50.0
3.Glycerin 10.0
4. Neem extract of Production Example 1 0.5
5. Rita extract of Production Example 3 0.5
6. Sodium lauryl sulfate 2.0
7.Saccharin sodium 0.05
8.Carboxymethylcellulose sodium 1.5
9. Fragrance (cardamon water) appropriate amount
10. Preservative (phenoxyethanol) appropriate amount
11.Coloring agent appropriate amount
12.Residue with 100 purified water

(Formulation Example 4) Mouthwash
weight%
1.Ethanol 20.0
2.Saccharin sodium 0.1
3.Sodium fluoride 0.1
4.Ascorbic acid 0.1
5.Sodium pyrithione 0.5
6.Benzethonium chloride 0.1
7. Proteoglycan of Production Example 4 1.0
8. Preservative (methylparaben) appropriate amount
9. Fragrance (Peppermint water)
10.Coloring agent appropriate amount
11. Residue with 100 purified water

(Formulation Example 5) Mouthwash
weight%
1.Ibuprofen 0.1
2.Ethanol 10.0
3.Polyoxyethylene hydrogenated castor oil 0.5
4.Sodium lauryl sulfate 0.5
5.Saccharin sodium 0.5
6.Glycerin 10.0
7. Proteoglycan of Production Example 4 3.0
8. Preservative (methylparaben) appropriate amount
9. Perfume (lime water) appropriate amount
10.Coloring agent appropriate amount
11. Residue with 100 purified water

(Formulation example 6) mouth freshener
weight%
1.Ethanol 20.0
2.Glycerin 15.0
3. Polyoxyethylene hydrogenated castor oil 1.0
4.Saccharin 0.2
5.Chlorohexidine 0.01
6. A: Neem extract of Production Example 1 B: Chrysanthemum extract of Production Example 2 C: Production Example 3 Rita extract D: Production Example 4 proteoglycan * any one of A to D 1.0
7. Grapefruit fruit hot water extract 0.5
8. Preservative (methylparaben) appropriate amount
9.Coloring agent appropriate amount
10. Residue with 100 purified water

(Formulation example 7) Chewing gum
weight%
1.Plate gum base 24.0
2. Minamata 13.0
3.Powdered sugar 60.0
4. Korean thistle extract from Production Example 2 1.0
5. Proteoglycan of Production Example 4 1.0
6. Preservative (methyl paraben) appropriate amount
7. Fragrance (Peppermint water)
8. Residue with 100 purified water

(Prescription Example 8) Candy
weight%
1.Granulated sugar 45.0
2.Water tank 41.0
3.Powdered sugar 60.0
4. Neem whole plant hot water extract 1.0
5. Preservative (methyl paraben) appropriate amount
6. Fragrance (Apple water)
7. Residue with 100 purified water

  The present invention finds that neem extract, daffodil extract, rita extract, proteoglycan inhibits periodontal disease bacteria, and, for neem extract, rita extract, further inhibits Candida, It can be applied as a periodontal disease inhibitor, a Candida inhibitor, or an oral composition.

Claims (3)

An inhibitor of periodontal disease bacteria, comprising Rita extract as an active ingredient. Periodontal pathogens include Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphylomonas gingivalis, and at least Prevotera intermedia (Prevotera intermedia) The periodontal disease bacteria inhibitor of Claim 1 which has an inhibitory action with respect to 1 or more types of periodontal disease bacteria. Oral compositions containing Rita extract as an active ingredient of periodontal bacteria suppressed.

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