JP2019214538A - Agent for inhibiting entry of periodontal disease bacteria into gingival tissue cell - Google Patents
Agent for inhibiting entry of periodontal disease bacteria into gingival tissue cell Download PDFInfo
- Publication number
- JP2019214538A JP2019214538A JP2018113466A JP2018113466A JP2019214538A JP 2019214538 A JP2019214538 A JP 2019214538A JP 2018113466 A JP2018113466 A JP 2018113466A JP 2018113466 A JP2018113466 A JP 2018113466A JP 2019214538 A JP2019214538 A JP 2019214538A
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- JP
- Japan
- Prior art keywords
- periodontal disease
- agent
- gingival tissue
- disease bacteria
- tissue cells
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Cosmetics (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
本発明は、歯肉組織細胞への歯周病菌の侵入抑制剤に関する。 The present invention relates to an agent for inhibiting periodontal disease bacteria from entering gingival tissue cells.
歯周病はほとんどの成人に罹病する可能性があるとされており、高齢化が進む現在における罹病率は益々増加する傾向にある。歯周病は、細菌性由来の炎症性疾患であり、具体的には、細菌の組織内侵入及び感染に対する宿主応答がその原因となっている。特にポルフィロモナス・ジンジバリス（Ｐｏｒｐｈｙｒｏｍｏｎａｓ ｇｉｎｇｉｖａｌｉｓ）は、歯周病の中で最も多いとされる成人性歯周病の病原菌と有力視されている細菌である。この細菌は、マトリックスメタロプロテアーゼ等の、歯周組織のコラーゲンを分解する酵素を産生することが知られている。 It is believed that periodontal disease can affect most adults, and the morbidity at present as the population ages tends to increase. Periodontal disease is an inflammatory disease of bacterial origin, specifically due to host response to bacterial invasion and infection. In particular, Porphyromonas gingivalis is a bacterium that is considered to be the causative bacterium of adult periodontal disease, which is considered to be the most common periodontal disease. This bacterium is known to produce enzymes, such as matrix metalloproteases, that degrade collagen in periodontal tissue.
このような歯周病に対処する処方がなされた口腔用組成物が種々知られている。例えば、特許文献１には、月桂樹葉抽出物が７０〜９０％エタノールで抽出されたものであることを特徴とする抗歯周病剤が開示されている。また、特許文献２には、茶由来重合カテキンを含有するマトリックスメタロプロテアーゼ1活性阻害組成物及び／又はマトリックスメタロプロテアーゼ３活性阻害組成物が開示されている。さらに、特許文献３には、バナバ葉、土荊皮（ドケイヒ）、川揀皮（センレンヒ）、薯良（ショリョウ）、拳参（ケンジン）、白胡椒、黒胡椒、小薊（ショウケイ）、蕪夷（ブイ）よりなる群から選択される少なくとも１種の抽出エキスを含有することを特徴とする、グルコシルトランスフェラーゼ阻害作用又は歯周病原菌ポルフィロモナス・ジンジバリス（Ｐｏｒｐｈｙｒｏｍｏｎａｓ ｇｉｎｇｉｖａｌｉｓ）生育阻害作用のいずれかを有する口腔用組成物が開示されている。 There are known various oral compositions that are formulated to cope with such periodontal disease. For example, Patent Literature 1 discloses an anti-periodontal agent characterized in that laurel leaf extract is extracted with 70 to 90% ethanol. Patent Document 2 discloses a matrix metalloprotease 1 activity inhibitory composition and / or a matrix metalloprotease 3 activity inhibitory composition containing a tea-derived polymerized catechin. Further, Patent Literature 3 discloses banaba leaf, dojihi, senrenhi, senryo, shogan, kenjin, white pepper, black pepper, shokei, and turnip. Any of a glucosyltransferase inhibitory action or a periodontal pathogen Porphyromonas gingivalis growth inhibitory action, characterized by containing at least one extracted extract selected from the group consisting of buoys. Oral compositions having the same are disclosed.
一方、ヒノキチオールは、殺菌作用を有する成分として知られており、口腔用組成物に配合されることがある。例えば特許文献４及び特許文献５には、ヒノキチオールが配合された口腔用組成物が開示されている。 On the other hand, hinokitiol is known as a component having a bactericidal action, and is sometimes added to an oral composition. For example, Patent Documents 4 and 5 disclose oral compositions in which hinokitiol is blended.
ヒノキチオールは、抗菌剤として知られてはいるものの、口腔用組成物として配合される濃度において歯周病菌に対する殺菌作用は高くない。歯周病菌に対して有効な殺菌作用を生じさせるためには、ヒノキチオールに対し、その抗菌性を増強させる添加物を配合する必要がある。そのため、単に抗菌性を増強させるアプローチでは処方に制約があり、近年の多様化する口腔用組成物の処方に対応できないケースがある。 Although hinokitiol is known as an antibacterial agent, it does not have a high bactericidal effect against periodontal disease bacteria at a concentration incorporated as an oral composition. In order to produce an effective bactericidal action against periodontal disease bacteria, it is necessary to add an additive to hinokitiol to enhance its antibacterial properties. Therefore, there is a case where it is not possible to cope with the recent diversification of the formulation of the oral composition because the formulation is restricted by the approach of simply enhancing the antibacterial property.
そこで本発明は、抗菌作用とは異なる作用機序により歯周病菌にアプローチができる剤を提供することを目的とする。 Therefore, an object of the present invention is to provide an agent capable of approaching periodontal disease bacteria by an action mechanism different from the antibacterial action.
本発明者は鋭意検討の結果、ヒノキチオールに、歯肉組織細胞への歯周病菌の進入を抑制する作用があることを見出した。本発明は、この知見に基づいてさらに検討を重ねることにより完成したものである。 As a result of intensive studies, the present inventor has found that hinokitiol has an effect of suppressing the invasion of periodontal disease bacteria into gingival tissue cells. The present invention has been completed by further study based on this finding.
即ち、本発明は、下記に掲げる態様の発明を提供する。
項１． ヒノキチオールを含有することを特徴とする、歯肉組織細胞への歯周病菌の侵入抑制剤。
項２． 更にシャクヤクエキスを含有する、項１に記載の歯肉組織細胞への歯周病菌の侵入抑制剤。
項３． 前記シャクヤクエキスの含有量が０．０００１〜０．０５重量％である、項２に記載の歯肉組織細胞への歯周病菌の侵入抑制剤。
項４． 前記ヒノキチオール１重量部当たりの前記シャクヤクエキスの含有量が、０．０１〜１重量部である、項２又は３に記載の歯肉組織細胞への歯周病菌の侵入抑制剤。
項５． 液体歯磨剤、液状歯磨剤、練歯磨剤、洗口液、口中清涼剤、又は口腔用軟膏剤からなる群より選択される口腔用組成物である、項１〜４のいずれかに記載の歯肉組織細胞への歯周病菌の侵入抑制剤。
That is, this invention provides the invention of the aspect hung up below.
Item 1. An agent for suppressing invasion of periodontal disease bacteria into gingival tissue cells, comprising hinokitiol.
Item 2. Item 3. The agent for suppressing invasion of periodontal disease bacteria into gingival tissue cells according to Item 1, further comprising a peony extract.
Item 3. Item 3. The agent for suppressing invasion of periodontal disease bacteria into gingival tissue cells according to Item 2, wherein the content of the peony extract is 0.0001 to 0.05% by weight.
Item 4. Item 4. The agent for suppressing invasion of periodontal disease bacteria into gingival tissue cells according to Item 2 or 3, wherein the content of the peony extract per 1 part by weight of the hinokitiol is 0.01 to 1 part by weight.
Item 5. The gingiva according to any one of Items 1 to 4, which is an oral composition selected from the group consisting of a liquid dentifrice, a liquid dentifrice, a toothpaste, a mouthwash, a mouthwash, or an oral ointment. Inhibitor of periodontal disease invasion into tissue cells.
本発明によれば、抗菌作用とは異なる作用機序により歯周病菌にアプローチができる剤として、歯肉組織細胞への歯周病菌の侵入抑制剤が提供される。 ADVANTAGE OF THE INVENTION According to this invention, the agent which can approach periodontal disease bacteria to a gingival tissue cell is provided as an agent which can approach periodontal disease bacteria by an action mechanism different from an antibacterial effect.
本発明の歯肉組織細胞への歯周病菌の侵入抑制剤は、ヒノキチオールを含有することを特徴とする。以下、本発明の歯肉組織細胞への歯周病菌の侵入抑制剤について詳述する。 The agent of the present invention for inhibiting periodontal disease bacteria from entering gingival tissue cells is characterized by containing hinokitiol. Hereinafter, the agent for inhibiting the invasion of periodontal disease bacteria into gingival tissue cells of the present invention will be described in detail.
ヒノキチオール
ヒノキチオールは、β−ツヤプリンとも呼ばれる不飽和７員環化合物であり、公知の成分である。ヒノキチオールとしては、天然物由来のものを使用してもよいし、化学合成されたものを使用してもよい。また、本発明で使用されるヒノキチオールは、精製品又は粗精製品の別を問わず、例えば、ヒノキ、ヒバ等の樹木から得られたヒノキチオール含有精油を使用することもできる。
Hinokitiol Hinokitiol is an unsaturated 7-membered ring compound, also called β-purine, and is a known component. As the hinokitiol, a natural product or a chemically synthesized product may be used. The hinokitiol used in the present invention may be a hinokitiol-containing essential oil obtained from trees such as hinoki and hiba, regardless of whether it is a purified product or a crude product.
本発明の歯肉組織細胞への歯周病菌の侵入抑制剤におけるヒノキチオールの配合量については、当該歯肉組織細胞への歯周病菌の侵入抑制剤の製剤形態や用途等に応じて適宜設定されるが、通常０．０２〜０．２重量％が挙げられる。歯肉組織細胞への歯周病菌の侵入抑制効果をより高める観点から、歯肉組織細胞への歯周病菌の侵入抑制剤におけるヒノキチオールの配合量としては、好ましくは０．０３〜０．２重量％、更に好ましくは０．０４〜０．２重量％が挙げられる。また、本発明の歯肉組織細胞への歯周病菌の侵入抑制剤は、ヒノキチオールが単独では歯周病菌に対する抗菌作用を示さない低濃度であっても、効果的に歯肉組織細胞への歯周病菌の侵入抑制作用を発揮することができる。このような本発明の効果をより好ましく得る観点から、本発明の歯肉組織細胞への歯周病菌の侵入抑制剤におけるヒノキチオールの配合量としては、好ましくは０．０２〜０．１重量％、より好ましくは０．０２〜０．０８重量％が、更に好ましくは０．０２〜０．０６重量％が挙げられる。 The amount of hinokitiol in the agent for inhibiting periodontal disease bacteria into the gingival tissue cells of the present invention is appropriately set according to the formulation form and use of the agent for inhibiting periodontal disease bacteria from entering the gingival tissue cells. And usually 0.02 to 0.2% by weight. From the viewpoint of further enhancing the effect of inhibiting the invasion of periodontal disease bacteria into gingival tissue cells, the amount of hinokitiol in the agent for inhibiting the invasion of periodontal disease bacteria into gingival tissue cells is preferably 0.03 to 0.2% by weight. More preferably, the content is 0.04 to 0.2% by weight. In addition, the inhibitor of invasion of periodontal disease bacteria into gingival tissue cells of the present invention is effective even when hinokitiol alone has a low concentration that does not show an antibacterial effect on periodontal disease bacteria, Can exert the effect of suppressing the intrusion of the particles. From the viewpoint that the effects of the present invention can be more preferably obtained, the compounding amount of hinokitiol in the agent for inhibiting invasion of periodontal disease bacteria into gingival tissue cells of the present invention is preferably 0.02 to 0.1% by weight, Preferably 0.02 to 0.08% by weight, more preferably 0.02 to 0.06% by weight.
シャクヤクエキス
シャクヤクエキスは、医薬部外品原料規格に記載されており、公知の成分である。シャクヤクエキスには、ヒノキチオールと組み合わされた場合に抗菌活性を向上させる作用はない。しかしながら、本発明の歯肉組織細胞への歯周病菌の侵入抑制剤においては、シャクヤクエキスをヒノキチオールと組み合わせることで、歯肉組織細胞への歯周病菌の侵入抑制性を向上させることができる。
Peony extract The peony extract is described in the quasi-drug raw material standard and is a known component. Peony extract has no action to improve antimicrobial activity when combined with hinokitiol. However, in the agent for inhibiting the invasion of periodontal disease bacteria into gingival tissue cells of the present invention, by combining the peony extract with hinokitiol, the ability to inhibit the invasion of periodontal disease bacteria into gingival tissue cells can be improved.
シャクヤクエキスは、具体的には、シャクヤク（Ｐａｅｏｎｉａ ａｌｂｉｆｌｏｒａＰａｌｌｓ ｖａｒ. ｔｒｉｃｈｏｃａｒｐａ Ｂｕｎｇｅ）又はその他近縁植物（Ｐａｅｏｎｉａｃｅａｅ）の根に対して抽出溶媒を用いて抽出処理することにより得ることができる。シャクヤクエキスの抽出処理に使用される抽出溶媒としては、例えば、水；エタノール等の低級アルコール；１，３−ブチレングリコール等の多価アルコール；これらの混合液等の極性溶媒が挙げられ、好ましくは水、エタノール、１，３−ブチレングリコール、又はこれらの混合溶媒が挙げられ、好ましくは水、１，３−ブチレングリコール混合溶媒が挙げられる。 The peony extract can be specifically obtained by subjecting the roots of a peony (Paeonia albifloraPalls var. Trichocarpa Bunge) or other closely related plants (Paeoniacae) to an extraction treatment using an extraction solvent. Examples of the extraction solvent used for the extraction of the peony extract include water; lower alcohols such as ethanol; polyhydric alcohols such as 1,3-butylene glycol; and polar solvents such as a mixture thereof. Examples include water, ethanol, 1,3-butylene glycol, and a mixed solvent thereof, and preferably, a mixed solvent of water and 1,3-butylene glycol.
本発明の歯肉組織細胞への歯周病菌の侵入抑制剤にシャクヤクエキスを配合させるためには、上記の抽出溶媒による抽出物を濃縮した液体エキスを用いてもよいし、当該液体エキスからさらに抽出溶媒を蒸発又は凍結乾燥して得られる乾燥エキスを用いてもよい。液体エキスとしては、例えば、乾燥エキス換算で２〜６重量％のシャクヤクエキスを含む濃度のものを用いることができる。 In order to mix the peony extract with the agent for inhibiting the invasion of periodontal disease bacteria into the gingival tissue cells of the present invention, a liquid extract obtained by concentrating the extract with the above-mentioned extraction solvent may be used, or further extracted from the liquid extract. A dried extract obtained by evaporating or freeze-drying the solvent may be used. As the liquid extract, for example, a liquid extract containing 2 to 6% by weight of a peony extract in terms of a dry extract can be used.
本発明の歯肉組織細胞への歯周病菌の侵入抑制剤におけるシャクヤクエキスの配合量については、ヒノキチオールの含有量等に応じて適宜設定すればよいが、乾燥エキス換算量で、例えば０．０００１〜０．０５重量％が挙げられる、歯肉組織細胞への歯周病菌の侵入抑制性をより良好に向上させる観点から、好ましくは０．００１〜０．０４重超％、さらに好ましくは０．００５〜０．０２重量％が挙げられる。 The amount of the peony extract in the agent for inhibiting the invasion of periodontal disease bacteria into the gingival tissue cells of the present invention may be appropriately set according to the content of hinokitiol, etc. From the viewpoint of better improving the inhibition of periodontal disease bacteria into gingival tissue cells, for example, 0.05% by weight, preferably from 0.001 to more than 0.04% by weight, more preferably from 0.005 to 0.05% by weight. 0.02% by weight.
また、本発明の歯肉組織細胞への歯周病菌の侵入抑制剤において、ヒノキチオールとシャクヤクエキスとの比率については、前述する各含有量に応じて定まるが、歯肉組織細胞への歯周病菌の侵入抑制性をより良好に向上させる観点から、ヒノキチオール１重量部当たりシャクヤクエキスの含有量として、例えば０．０１〜１重量部、好ましくは０．１〜０．５重量部、より好ましくは０．１〜０．３重量部が挙げられる。 Further, in the agent for inhibiting the invasion of periodontal disease bacteria into gingival tissue cells of the present invention, the ratio of hinokitiol to the peony extract is determined according to each of the above-mentioned contents, but the invasion of periodontal disease bacteria into gingival tissue cells is determined. From the viewpoint of better improving the inhibitory property, the content of the peony extract per 1 part by weight of hinokitiol is, for example, 0.01 to 1 part by weight, preferably 0.1 to 0.5 part by weight, more preferably 0.1 to 0.1 part by weight. To 0.3 parts by weight.
その他の成分
本発明の歯肉組織細胞への歯周病菌の侵入抑制剤は、前述する成分以外に、本発明の効果を損なわない範囲で、口腔組成物分野において通常使用される成分を含有していてもよい。このような成分としては、例えば、防腐剤、殺菌剤、抗菌剤、消炎剤、研磨剤、グルコシルトランスフェラーゼ（ＧＴａｓｅ）阻害剤、プラーク抑制剤、知覚過敏抑制剤、歯石予防剤、歯質強化／再石灰化剤、抗ヒスタミン剤、局所麻酔剤、血行促進剤、増粘剤、湿潤剤、賦形剤、香料、甘味剤、清涼化剤、色素、消臭剤、界面活性剤、溶剤、ｐＨ調整剤等が挙げられる。なお、本発明の歯肉組織細胞への歯周病菌の侵入抑制剤は、ヒノキチオールによって発揮される歯肉組織細胞への歯周病菌の侵入抑制作用を利用するものであるため、ヒノキチオール自体の抗菌活性を向上させるための抗菌活性向上剤を含んでいなくても、歯肉組織細胞への歯周病菌の侵入抑制作用を有効に発揮することができる。
Other Ingredients The inhibitor of periodontal disease bacteria into the gingival tissue cells of the present invention contains, in addition to the above-mentioned components, components commonly used in the field of oral compositions, as long as the effects of the present invention are not impaired. May be. Such components include, for example, preservatives, bactericides, antibacterial agents, anti-inflammatory agents, abrasives, glucosyltransferase (GTase) inhibitors, plaque inhibitors, hyperesthesia inhibitors, tartar preventives, tooth strengthening / rebuilding agents Calcifying agents, antihistamines, local anesthetics, blood circulation promoters, thickeners, wetting agents, excipients, flavors, sweeteners, fresheners, pigments, deodorants, surfactants, solvents, pH adjusters, etc. Is mentioned. The agent for inhibiting the invasion of periodontal bacteria into gingival tissue cells of the present invention utilizes the action of inhibiting the invasion of periodontal disease bacteria into gingival tissue cells exerted by hinokitiol, so that the antibacterial activity of hinokitiol itself is reduced. Even if it does not contain an antibacterial activity enhancer for improving, it is possible to effectively exert the effect of suppressing the invasion of periodontal disease bacteria into gingival tissue cells.
防腐剤、殺菌剤、抗菌剤としては、例えば、安息香酸類、サリチル酸類、ソルビン酸類、パラベン類、塩化デカリニウム、塩化クロルヘキシジン、グルコン酸クロルヘキシジン、イソプロピルメチルフェノール、トリクロサン、塩化リゾチーム、塩酸クロルヘキシジン、ヨウ化カリウム等が挙げられる。 Preservatives, bactericides, antibacterial agents include, for example, benzoic acids, salicylic acids, sorbic acids, parabens, decalinium chloride, chlorhexidine chloride, chlorhexidine gluconate, isopropylmethylphenol, triclosan, lysozyme chloride, chlorhexidine hydrochloride, potassium iodide And the like.
消炎剤としては、例えば、グリチルリチン酸ジカリウム、グリチルレチン酸、グリチルリチン酸メチル、グリチルリチン酸ステアリル、グリチルレチン酸ピリドキシン、グリチルレチン酸ステアリル、グリチルレチン酸グリセリル、グリチルレチン酸モノグルクロニド、アラントイン、トラネキサム酸、イプシロンアミノカプロン酸、アズレン、塩化ナトリウム、ビタミン類等が挙げられる。 Anti-inflammatory agents, for example, dipotassium glycyrrhizinate, glycyrrhetinic acid, methyl glycyrrhizinate, stearyl glycyrrhizinate, pyridoxine glycyrrhetinate, stearyl glycyrrhetinate, glyceryl glyceryl, glycyrrhetinic acid monoglucuronide, allantoin, tranexamic acid, epsilon aminocaproic acid, azulene Examples include sodium chloride and vitamins.
研磨剤としては、例えば、無水ケイ酸、含水ケイ酸、酸化アルミニウム、水酸化アルミニウム、リン酸水素カルシウム、リン酸カルシウム、ピロリン酸カルシウム、炭酸カルシウム、結晶セルロース、ポリエチレン末、炭粒等が挙げられる。 Examples of the abrasive include silicic anhydride, hydrated silicic acid, aluminum oxide, aluminum hydroxide, calcium hydrogen phosphate, calcium phosphate, calcium pyrophosphate, calcium carbonate, crystalline cellulose, polyethylene powder, charcoal particles, and the like.
ＧＴａｓｅ阻害剤としては、例えば、アカバナ科マツヨイグサ属植物の抽出物、ブドウ科ブドウ属植物の抽出物、デキストラナーゼ、ムタナーゼ、タステイン、タンニン類、エラグ酸、ポリフェノール、ウーロン茶抽出物、緑茶抽出物、センブリ、タイソウ、ウイキョウ、ゲンチアナ、センソ、龍胆、黄連等が挙げられる。 Examples of the GTase inhibitor include, for example, extracts of plants of the genus Oenothera genus, extracts of vines of the genus Grape, dextranase, mutanase, tustein, tannins, ellagic acid, polyphenol, oolong tea extract, green tea extract, Assemblies, lyophiles, fennel, gentian, senso, dragon, and oren.
プラーク抑制剤としては、例えばクエン酸亜鉛やグルコン酸等が挙げられる。 Examples of the plaque inhibitor include zinc citrate and gluconic acid.
知覚過敏抑制剤としては、例えば、硝酸カリウム、塩化ストロンチウム等が挙げられる。 Examples of the hypersensitivity inhibitor include potassium nitrate and strontium chloride.
歯石予防剤としては、例えば、ポリリン酸塩類、ゼオライト、エタンヒドロキシジホスフォネート等が挙げられる。 Examples of the tartar preventive include polyphosphates, zeolite, ethanehydroxydiphosphonate and the like.
歯質強化／再石灰化剤としては、例えば、フッ素、フッ化ナトリウム、フルオロリン酸ナトリウム、フッ化第一スズ等が挙げられる。 Examples of the tooth strengthening / remineralizing agent include fluorine, sodium fluoride, sodium fluorophosphate, stannous fluoride and the like.
抗ヒスタミン剤としては、例えば、ジフェンヒドラミン、塩酸ジフェンヒドラミン等が挙げられる。 Examples of the antihistamine include diphenhydramine and diphenhydramine hydrochloride.
局所麻酔剤としては、例えば、プロカイン、テトラカイン、ブピパカイン、メピパカイン、クロロプロカイン、プロパラカイン、メプリルカイン又はこれらの塩、オルソカイン、オキセサゼイン、オキシポリエントキシデカン、ロートエキス、ペルカミンパーゼ、テシットデシチン等が挙げられる。 Examples of the local anesthetic include procaine, tetracaine, bupivacaine, mepipacaine, chloroprocaine, proparacaine, meprilcaine or a salt thereof, orthocaine, oxesazein, oxypolyentoxydecane, funnel extract, percaminpase, tesit desitin and the like.
血行促進剤としては、例えば、ノニル酸ワニリルアミド、ニコチン酸ベンジルエステル、カプサイシン、トウガラシエキス等が挙げられる。 Examples of the blood circulation promoting agent include nonyl acid varnishylamide, nicotinic acid benzyl ester, capsaicin, and pepper extract.
増粘剤としては、例えば、プルラン、プルラン誘導体、デンプン等の多糖類；ヒドロキシプロピルセルロース、ヒドロキシエチルセルロース、ヒドロキシプロピルメチルセルロース、ヒドロキシエチルメチルセルロース、カルボキシメチルセルロース、カルボキシメチルセルロース塩類（カルボキシメチルセルロースナトリウム、カルボキシメチルセルロースカリウム等）、メチルセルロース、エチルセルロース、ポリアクリル酸、ポリアクリル酸塩（ポリアクリル酸ナトリウム、アクリル酸・アクリル酸オクチルエステル共重合体等）、メタアクリル酸類の共重合体（メタアクリル酸とアクリル酸 ｎ−ブチルの重合体、メタアクリル酸とメタアクリル酸メチルの重合体及びメタアクリル酸とアクリル酸エチルの重合体等）等のセルロース系高分子物質；カルボキシビニルポリマー、ポリエチレングリコール、ポリビニルアルコール、ポリビニルピロリドン等の合成高分子物質；レクチン、アルギン酸、アルギン酸塩（アルギン酸ナトリウム、アルギン酸カリウム、アルギン酸マグネシウム、アルギン酸プロピレングリコールエステル、アルギン酸トリエタノールアミン、アルギン酸トリイソプロパノールアミン、アルギン酸アンモニウム、アルギン酸ブチルアミン、アルギン酸ジアミルアミン等）、コンドロイチン硫酸ナトリウム、寒天、キトサン、カラギーナン等の天然系高分子物質；コラーゲン、ゼラチン等のアミノ酸系高分子物質；アラビアガム、カラヤガム、トラガカントガム、キサンタンガム、ローカストビーンガム、グアガム、タマリンドガム、ジェランガム等のゴム系高分子物質等が挙げられる。 Examples of the thickener include polysaccharides such as pullulan, pullulan derivatives and starch; hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, hydroxyethylmethylcellulose, carboxymethylcellulose, and carboxymethylcellulose salts (such as sodium carboxymethylcellulose and potassium carboxymethylcellulose). , Methylcellulose, ethylcellulose, polyacrylic acid, polyacrylate (sodium polyacrylate, acrylic acid / octyl acrylate copolymer), and methacrylic acid copolymer (methacrylic acid and n-butyl acrylate) Cellulosics such as polymers, polymers of methacrylic acid and methyl methacrylate, and polymers of methacrylic acid and ethyl acrylate) Synthetic polymer such as carboxyvinyl polymer, polyethylene glycol, polyvinyl alcohol and polyvinylpyrrolidone; lectin, alginic acid, alginates (sodium alginate, potassium alginate, magnesium alginate, propylene glycol alginate, triethanolamine alginate, alginic acid) Triisopropanolamine, ammonium alginate, butylamine alginate, diamylamine alginate, etc.), sodium chondroitin sulfate, agar, chitosan, carrageenan, etc., natural polymer materials; collagen, gelatin, etc. amino acid polymer materials; arabic gum, karaya gum, tragacanth gum, Xanthan gum, locust bean gum, guar gum, tamarind gum, gellan gum, etc. System polymer material, and the like.
湿潤剤としては、例えば、グリセリン、ソルビトール、エチレングリコール、プロピレングリコール、ポリエチレングリコール、ポリプロピレングリコール、キシリトール、マルチトール、ラクトール、エリスリトール等が挙げられる。 Examples of the humectant include glycerin, sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, xylitol, maltitol, lactol, erythritol and the like.
賦形剤としては、例えば、乳糖、白糖、マンニトール、デンプン、デキストリン、結晶セルロース、シリカ（軽質無水ケイ酸等）等が挙げられる。 Examples of the excipient include lactose, sucrose, mannitol, starch, dextrin, crystalline cellulose, silica (light silicic anhydride and the like) and the like.
香料としては、例えば、天然香料（ウイキョウ油等）、合成香料、これらの調合香料等が挙げられる。 Examples of the fragrance include natural fragrances (eg, fennel oil and the like), synthetic fragrances, and compounded fragrances.
甘味剤としては、サッカリンナトリウム、ステビオサイド、ステビアエキス、アスパルテーム、キシリトール、水飴、蜂蜜、ソルビトール、マルチトール、マンニトール、エリスリトール、糖類（乳糖、白糖、果糖、ブドウ糖等）等が挙げられる。 Examples of the sweetener include saccharin sodium, stevioside, stevia extract, aspartame, xylitol, syrup, honey, sorbitol, maltitol, mannitol, erythritol, sugars (lactose, sucrose, fructose, glucose, etc.).
清涼化剤としては、例えば、メントール、エリスリトール、カンフル、ボルネオール、ゲラニオール、これらを含む精油等が挙げられる。 Examples of the cooling agent include menthol, erythritol, camphor, borneol, geraniol, and essential oils containing these.
色素としては、例えば、天然色素、合成色素、これらの混合物が挙げられる。 Examples of the dye include a natural dye, a synthetic dye, and a mixture thereof.
消臭剤としては、例えば、塩化亜鉛、銅クロロフィリンナトリウム、コーヒー生豆抽出物、ゴボウパウダー、緑茶、焙煎米糠エキス等が挙げられる。 Examples of the deodorant include zinc chloride, sodium copper chlorophyllin, green coffee bean extract, burdock powder, green tea, roasted rice bran extract and the like.
界面活性剤としては、例えば、ポリオキシエチレンラウリルエーテル硫酸ナトリウム、ラウリル硫酸ナトリウム、ミリスチル硫酸ナトリウム、Ｎ−ラウロイルサルコシン酸ナトリウム、Ｎ−ミリストリルサルコシン酸ナトリウム、ドデシルベンゼンスルホン酸ナトリウム、水素添加ココナッツ脂肪酸モノグリセリドモノ硫酸ナトリウム、ラウリルスルホ酢酸ナトリウム、α−オレフィンスルホン酸ナトリウム、Ｎ−パルミトイルグルタルミン酸ナトリウム、Ｎ−メチル−Ｎ−アシルタウリンナトリウム等の陰イオン性界面活性剤；ポリオキシエチレン硬化ヒマシ油、ショ糖脂肪酸エステル、マルトース脂肪酸エステル、マルチトール脂肪酸エステル、ラクトール脂肪酸エステル、ソルビタン脂肪酸エステル、ポリオキシエチレンソルビタンモノステアレート、ポリオキシエチレン高級アルコールエーテル、ポリオキシエチレンポリオキシプロピレン共重合体、ポリオキシエチレンポリオキシプロピレン脂肪酸エステル、ポリグリセリン脂肪酸エステル等の非イオン性界面活性剤；ヤシ油脂肪酸アミドプロピルベタイン、ラウリルジメチルアミノ酢酸ベタイン、ラウリルジメチルアミンオキシド、２-アルキル−Ｎ−カルボキシメチル−Ｎ−ヒドロキシエチルイミダゾリウムベタイン、Ｎ−ラウリルジアミノエチルグリシン、Ｎ−ミリスチルジアミノエチルグリシン、Ｎ−アルキル−１−ヒドロキシエチルイミダゾリンベタインナトリウム等の両性界面活性剤；塩化ラウリルトリメチルアンモニウム、塩化ステアリルトリメチルアンモニウム、塩化ベンゼトニウム、塩化ベンザルコニウム、塩化ステアリルジメチルベンジルアンモニウム等の陽イオン性界面活性剤が挙げられる。 Examples of the surfactant include sodium polyoxyethylene lauryl ether sulfate, sodium lauryl sulfate, sodium myristyl sulfate, sodium N-lauroyl sarcosinate, sodium N-myristoryl sarcosine, sodium dodecylbenzenesulfonate, hydrogenated coconut fatty acid monoglyceride. Anionic surfactants such as sodium monosulfate, sodium lauryl sulfoacetate, sodium α-olefin sulfonate, sodium N-palmitoyl glutamate, sodium N-methyl-N-acyl taurate; polyoxyethylene hydrogenated castor oil, Sugar fatty acid ester, maltose fatty acid ester, maltitol fatty acid ester, lactol fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan Nonionic surfactants such as stearate, polyoxyethylene higher alcohol ether, polyoxyethylene polyoxypropylene copolymer, polyoxyethylene polyoxypropylene fatty acid ester, polyglycerin fatty acid ester; coconut oil fatty acid amidopropyl betaine, lauryl Betaine dimethylaminoacetate, lauryl dimethylamine oxide, 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolium betaine, N-lauryldiaminoethylglycine, N-myristyldiaminoethylglycine, N-alkyl-1-hydroxyethylimidazoline Amphoteric surfactants such as betaine sodium; lauryl trimethyl ammonium chloride, stearyl trimethyl ammonium chloride, benzethonium chloride, benzalkonium chloride , Cationic surfactants such as chloride stearyl dimethyl benzyl ammonium.
溶剤としては、例えば、水、エタノール、プロパノール、ブタノール、ペンタノール、ヘキサノール、イソプロパノール等の１価アルコール等が挙げられる。 Examples of the solvent include water, monohydric alcohols such as ethanol, propanol, butanol, pentanol, hexanol, and isopropanol.
ｐＨ調整剤としては、例えば、酢酸、塩酸、硫酸、硝酸、クエン酸、リンゴ酸、乳酸、リン酸、安息香酸、水酸化ナトリウム、水酸化カリウム、酢酸ナトリウム、炭酸ナトリウム、クエン酸ナトリウム、クエン酸水素ナトリウム、乳酸ナトリウム、乳酸カルシウム、リン酸ナトリウム、リン酸水素ナトリウム、安息香酸ナトリウム等が挙げられる。 Examples of the pH adjuster include acetic acid, hydrochloric acid, sulfuric acid, nitric acid, citric acid, malic acid, lactic acid, phosphoric acid, benzoic acid, sodium hydroxide, potassium hydroxide, sodium acetate, sodium carbonate, sodium citrate, and citric acid Examples thereof include sodium hydrogen, sodium lactate, calcium lactate, sodium phosphate, sodium hydrogen phosphate, and sodium benzoate.
本発明の歯肉組織細胞への歯周病菌の侵入抑制剤において、これらの成分を含有させる場合、その含有量については、当該技術分野で通常使用される範囲で適宜設定すればよい。 When these components are contained in the agent for suppressing periodontal disease into gingival tissue cells of the present invention, the content thereof may be appropriately set within a range usually used in the technical field.
ｐＨ
また、本発明の歯肉組織細胞への歯周病菌の侵入抑制剤のｐＨについては、口腔内への適用が許容される範囲で適宜設定すればよいが、例えば、４〜８、好ましくは５〜７．５、更に好ましくは６〜７が挙げられる。ここで、ｐＨとは、２５℃の温度条件下で測定される値である。
pH
Further, the pH of the agent for inhibiting the invasion of periodontal disease bacteria into the gingival tissue cells of the present invention may be appropriately set within a range in which application to the oral cavity is permissible, for example, 4 to 8, preferably 5 to 5. 7.5, and more preferably 6 to 7. Here, the pH is a value measured under a temperature condition of 25 ° C.
製剤形態
本発明の歯肉組織細胞への歯周病菌の侵入抑制剤の形状については、特に制限されず、液状、固形状、半固形状（ゲル状、軟膏状、ペースト状）等のいずれであってもよい。
Formulation Form The shape of the agent for inhibiting the invasion of periodontal disease bacteria into the gingival tissue cells of the present invention is not particularly limited, and may be any of liquid, solid, semi-solid (gel, ointment, paste) and the like. May be.
本発明の歯肉組織細胞への歯周病菌の侵入抑制剤は、口腔内に適用されて口腔内で一定時間滞留し得る口腔用組成物である限り、可食性、非可食性の別を問わない。本発明の歯肉組織細胞への歯周病菌の侵入抑制剤は、例えば、口腔衛生剤、食品（機能性食品、健康保健用食品、病者用食品等を含む）、医薬品（医薬部外品を含む）、化粧品等のいずれの形態であってもよい。本発明の歯肉組織細胞への歯周病菌の侵入抑制剤の製剤形態として、具体的には、液体歯磨剤、液状歯磨剤、練歯磨剤、潤製歯磨剤、粉歯磨剤、洗口剤（マウスウォッシュ）、マウスリンス、含嗽剤、口中清涼剤（マウススプレー等）、口腔用パスタ剤、歯肉マッサージクリーム、口腔咽候薬（トローチ剤等）等の口腔衛生剤；可食性フィルム、チューインガム、キャンディ、グミキャンディ、タブレット、顆粒、細粒、粉末、カプセル等の可食性口腔用剤；口腔用軟膏剤、口腔内付着錠剤等の医薬品等が挙げられる。これらの中でも、口腔衛生剤及び医薬品は、歯肉組織に対して、ヒノキチオールに基づく歯周病菌の侵入抑制作用を付与し易く、好適な製剤形態である。口腔衛生剤の中でも、好ましくは液体歯磨剤、液状歯磨剤、練歯磨剤、洗口液、口中清涼剤が挙げられ、医薬品の中でも、好ましくは口腔用軟膏剤が挙げられる。 The agent for inhibiting the invasion of periodontal disease bacteria into the gingival tissue cells of the present invention is not limited to edible or non-edible as long as it is an oral composition that can be applied to the oral cavity and stay in the oral cavity for a certain period of time. . The agent of the present invention for inhibiting the invasion of periodontal disease bacteria into gingival tissue cells includes, for example, oral hygiene agents, foods (including functional foods, foods for health and health, foods for the sick, etc.), pharmaceuticals (quasi-drugs). And cosmetics and the like. Specific examples of the formulation of the agent of the present invention for inhibiting the invasion of periodontal disease bacteria into gingival tissue cells include liquid dentifrice, liquid dentifrice, toothpaste, lubricating dentifrice, powder dentifrice, mouthwash ( Mouthwash), mouth rinse, mouthwash, mouthwash (mouth spray, etc.), oral pasta, gingival massage cream, oropharyngeal medicine (troche, etc.); oral hygiene; edible film, chewing gum, candy Edible oral preparations such as gummy candy, gummy candy, tablets, granules, fine granules, powders, capsules and the like; and pharmaceuticals such as oral ointments and intraorally adhered tablets. Among these, oral hygiene agents and pharmaceuticals are easy to impart to gingival tissue an action of inhibiting the invasion of periodontal disease bacteria based on hinokitiol, and are in a preferred formulation. Of the oral hygiene agents, liquid dentifrices, liquid dentifrices, toothpastes, mouthwashes, mouth fresheners are preferable, and among pharmaceuticals, oral ointments are preferable.
製造方法
本発明の歯肉組織細胞への歯周病菌の侵入抑制剤は、前述するヒノキチオール、及び必要に応じて配合されるシャクヤクエキス、並びに必要に応じて配合される他の成分を配合して、その製剤形態に応じた所定の形状に調製することによって製造できる。
The method for inhibiting the invasion of periodontal disease bacteria into the gingival tissue cells of the production method of the present invention comprises the above-mentioned hinokitiol, and the peony extract that is blended if necessary, and other components that are blended if necessary. It can be manufactured by preparing into a predetermined shape according to the formulation.
用途
本発明の歯肉組織細胞への歯周病菌の侵入抑制剤は、歯肉組織細胞への歯周病菌の侵入抑制を目的として使用することができる。具体的には、歯周病の予防及び治療に使用することができる。また、本発明の歯肉組織細胞への歯周病菌の侵入抑制剤は、ヒノキチオールが単独では歯周病菌に対する抗菌作用を示さない低濃度であっても、効果的に歯肉組織細胞への歯周病菌の侵入抑制作用を発揮することができるため、抗菌性の強い口腔用組成物を忌避する人に対しては、人体に優しい成分でありながらも歯周病の予防及び治療が可能となる点で特に好適に使用される。
Use The agent for inhibiting the invasion of periodontal disease bacteria into gingival tissue cells of the present invention can be used for the purpose of suppressing the invasion of periodontal disease bacteria into gingival tissue cells. Specifically, it can be used for prevention and treatment of periodontal disease. In addition, the inhibitor of invasion of periodontal disease bacteria into gingival tissue cells of the present invention is effective even when hinokitiol alone has a low concentration that does not show an antibacterial effect on periodontal disease bacteria, Because it can exert the effect of inhibiting the invasion of, for those who repel the oral composition having a strong antibacterial property, it is possible to prevent and treat periodontal disease while being a component friendly to the human body. Particularly preferably used.
本発明の歯肉組織細胞への歯周病菌の侵入抑制剤の用量としては、製剤形態及び適用する症状の程度等に応じて適宜設定すればよい。例えば、口腔用衛生剤の場合、１日数回、通常の口腔用衛生剤と同様に口腔内に適用することができる。また、医薬品の場合、１回当たり、ヒノキチオールが０．０６〜０．６ｍｇとなる量で、１日１〜数回程度の頻度で適用することができる。 The dose of the agent for inhibiting the invasion of periodontal disease bacteria into the gingival tissue cells of the present invention may be appropriately set depending on the form of the preparation, the degree of symptoms to be applied, and the like. For example, in the case of an oral hygiene, it can be applied to the oral cavity several times a day in the same manner as a normal oral hygiene. In addition, in the case of pharmaceuticals, hinokitiol can be applied in an amount of 0.06 to 0.6 mg per time, at a frequency of about one to several times a day.
以下に実施例を示して本発明をより具体的に説明するが、本発明はこれらに限定されるものではない。 Hereinafter, the present invention will be described more specifically with reference to Examples, but the present invention is not limited thereto.
試験例１
表１に示す組成の被験試料を歯肉組織細胞への歯周病菌の侵入抑制剤として調製した。シャクヤクエキス凍結乾燥粉末として、丸善製薬社製（シャクヤク抽出物ＢＧ−ＪＣ）を用いた。歯肉組織細胞として、Ｊａｐａｎｅｓｅ Ｃｏｌｌｅｃｔｉｏｎ ｏｆ Ｒｅｓｅａｒｃｈ Ｂｉｏｒｅｓｏｕｃｅｓ（ＪＣＲＢ）細胞バンクより入手した歯肉上皮細胞Ｃａ９−２２を用い、試験菌として、Ｐｏｒｐｈｙｒｏｍｏｎａｓ ｇｉｎｇｉｖａｌｉｓ（ＪＣＭ １２２５７；以下においてＰ．ｇ．菌と記載する）を用い、以下の方法によって、歯肉組織細胞への歯周病菌の侵入抑制の程度を評価した。
Test example 1
A test sample having the composition shown in Table 1 was prepared as an agent for suppressing invasion of periodontal disease bacteria into gingival tissue cells. As a lyophilized powder of a peony extract, a product of Maruzen Pharmaceutical Co., Ltd. (Peony extract BG-JC) was used. As gingival tissue cells, gingival epithelial cells Ca9-22 obtained from the Japan Collection of Research Bioresources (JCRB) cell bank were used, and Porphyromonas gingivalis (JCM 12257; hereinafter referred to as Pg bacteria) was used as a test bacterium. The degree of suppression of invasion of periodontal disease bacteria into gingival tissue cells was evaluated by the following method.
１．歯肉上皮細胞を、ＣＯ2インキュベーターを用い、５ｖ／ｖ％ＣＯ2の雰囲気下、ＭＥＭ培地（Ｇｉｂｃｏ）にて３７℃で１日間インキュベートした。
２．Ｐ．ｇ．菌をＭＥＭ培地に懸濁して被験試料と混合したものを、歯肉上皮細胞に添加し、２時間インキュベートした。
３．上清を除去し、抗菌剤処理にて細胞に付着した菌を除去した。
４．細胞を破裂させ、細胞内に侵入した菌を取り出し、段階希釈後、寒天培地にて３７℃で混釈培養した。
５．２週間培養後の寒天培地で生育したコロニー形成単位（ＣＦＵ）をカウントした。
1. Gingival epithelial cells were incubated for 1 day at 37 ° C. in MEM medium (Gibco) using a CO 2 incubator under an atmosphere of 5 v / v% CO 2 .
2. P. g. A mixture of the bacteria suspended in a MEM medium and a test sample was added to the gingival epithelial cells and incubated for 2 hours.
3. The supernatant was removed, and the bacteria attached to the cells were removed by the antibacterial treatment.
4. The cells were ruptured, the bacteria that had entered the cells were taken out, serially diluted, and then pour-cultured at 37 ° C. on an agar medium.
5. The number of colony forming units (CFU) grown on the agar medium after culturing for 2 weeks was counted.
結果を表１に示す。表１において、コロニー形成単位は、２回の試験の平均値である。表１から明らかなとおり、ヒノキチオールを含まない比較例（コントロール）と比べ、ヒノキチオールを含む実施例１及び２では、歯肉上皮細胞へ侵入したＰ．ｇ．菌の数が顕著に減少していた。つまり、ヒノキチオールによる、Ｐ．ｇ．菌の歯肉上皮細胞への顕著な抑制効果が認められた。また、Ｐ．ｇ．菌の歯肉上皮細胞への侵入抑制効果は、ヒノキチオール濃度の濃度がより低い０．０２重量％、０．０３重量％、及び０．０４重量％の場合でも認められ、これらの中では、０．０３重量％、及び０．０４重量％の場合に良好に認められた。さらに、０．０３重量％、及び０．０４重量％の中では、０．０４重量％の場合に一層良好に認められ、０．０４重量％の場合における効果の程度は、ヒノキチオールが０．０５重量％の実施例１と同程度であった。さらに、ヒノキチオールを含む実施例１と比べ、更にシャクヤクエキスを含む実施例２では、歯肉上皮細胞へ侵入したＰ．ｇ．菌の数の更に顕著な減少が認められた。なお、ヒノキチオールにシャクヤクエキスを組み合わせても、Ｐ．ｇ．菌の殺菌作用を向上させる効果は認められなかった。しかしながら、実施例２に示す通り、ヒノキチオールにシャクヤクエキスを組み合わせることで歯肉組織細胞への侵入抑制性を顕著に向上させることが可能であり、歯肉組織細胞への歯周病菌の侵入抑制剤として一層好適であることが示された。 The results are shown in Table 1. In Table 1, the colony forming units are the average of two tests. As is clear from Table 1, in Examples 1 and 2 containing hinokitiol as compared with the comparative example (control) not containing hinokitiol, P. invaginated into gingival epithelial cells. g. The number of bacteria was significantly reduced. That is, P. by hinokitiol. g. A remarkable inhibitory effect of the bacteria on gingival epithelial cells was observed. Also, P.I. g. The effect of inhibiting the invasion of bacteria to the gingival epithelial cells is observed even when the hinokitiol concentration is lower, at 0.02% by weight, 0.03% by weight, and 0.04% by weight. It was well recognized at 03% by weight and 0.04% by weight. Further, among 0.03% by weight and 0.04% by weight, the case of 0.04% by weight is better recognized, and the degree of the effect at 0.04% by weight is as follows. % By weight. Furthermore, as compared with Example 1 containing hinokitiol, in Example 2 further containing a peony extract, P. invaginated into gingival epithelial cells. g. A further significant decrease in the number of bacteria was observed. In addition, even if the peony extract is combined with hinokitiol, P. g. No effect of improving the bactericidal action of the bacteria was observed. However, as shown in Example 2, the combination of hinokitiol with a peony extract can significantly improve the ability to inhibit invasion into gingival tissue cells, and as a suppressant for periodontal disease invasion into gingival tissue cells. It has been shown to be suitable.
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| JP7204846B1 (en) | 2021-08-31 | 2023-01-16 | サンスター株式会社 | Hinokitiol-containing composition |
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