JP5099617B2 - Periodontal disease preventive and therapeutic agent - Google Patents
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本発明は、β−クリプトキサンチンやβ−クリプトキサンチン含有組成物を有効成分とする歯周病の予防あるいは症状改善効果を発揮しうる歯周病の予防・治療剤や、β−クリプトキサンチンを有効成分として含有する歯周病の予防・治療用の口腔用組成物に関する。 The present invention is effective for the prevention and treatment of periodontal disease that can exhibit periodontal disease prevention or symptom improvement effect, and β-cryptoxanthin, which comprises β-cryptoxanthin or a composition containing β-cryptoxanthin as an active ingredient. It relates to oral compositions for the prevention and treatment of periodontal disease containing as an ingredient.
歯周病は、歯の表面についた汚れ（プラーク）により、歯を支えている歯ぐきや骨が、化膿したり破壊されたりする病気であり、日本国民の８割が罹患する国民病疾患である。高齢化社会を迎えたわが国において、歯周病は中高年齢者が歯を失う主な原因となっており、歯を健康に保つことは国内外を問わず健康上の重要な課題となっている。歯周病の治療方法としては外科的治療方法や、ペリオクリンやファンキゾンという抗生物質による薬物治療法や、チアゾール化合物もしくはその薬学的に許容される塩からなる骨粗鬆症、骨折、歯周病等、種々の骨疾病・障害の治療薬（例えば、特許文献１参照）や、抗ＣＤ１４抗体を有効成分として含有する歯周病治療薬（例えば、特許文献２参照）や、血管内皮細胞増殖因子／血管透過性因子（ＶＥＧＦ／ＶＰＦ）に対する抗体を含む製剤からなることを特徴とする歯周病治療薬（例えば、特許文献３参照）等が知られている。 Periodontal disease is a disease in which the gums and bones supporting the teeth are suppurated or destroyed by dirt (plaque) on the tooth surface, and is a national disease that affects 80% of the Japanese population. . Periodontal disease is a major cause of losing teeth among middle-aged and elderly people in Japan, which is facing an aging society, and keeping teeth healthy is an important health issue both in Japan and overseas . Various treatment methods for periodontal diseases include surgical treatment methods, drug treatment methods using antibiotics such as periocrine and funkisone, osteoporosis, fractures and periodontal diseases consisting of thiazole compounds or pharmaceutically acceptable salts thereof. A therapeutic agent for bone diseases / disorders (for example, see Patent Document 1), a therapeutic agent for periodontal disease containing an anti-CD14 antibody as an active ingredient (for example, see Patent Document 2), vascular endothelial growth factor / vascular permeability A therapeutic agent for periodontal disease (for example, see Patent Document 3) characterized by comprising a preparation containing an antibody against a factor (VEGF / VPF) is known.
また、歯周病の予防や治療に有用な物質を評価する方法としては、歯垢が付着しやすくなるように、動物の歯の周りに糸を巻いて装着し、数ヶ月放置して歯周病を発症させ、その後、歯周組織を摘出して切片を作製し、形態学的に観察して評価する、自然発症モデルを用いる方法（例えば、非特許文献１参照）や、ヒト歯周病菌の生きた菌を動物に投与して感染させて発症させる歯周病菌を投与する方法（例えば、非特許文献２参照）等が報告されている。 In addition, as a method for evaluating substances useful for the prevention and treatment of periodontal disease, a thread is wound around an animal's tooth so that plaque easily adheres to it, and it is left for several months. A method using a spontaneous onset model (see, for example, Non-Patent Document 1) or a human periodontal disease bacteria that develops a disease, then extracts a periodontal tissue to prepare a section, and observes and evaluates morphologically A method of administering periodontal disease bacteria that develop by infecting animals by infecting them with live bacteria (for example, see Non-patent Document 2) has been reported.
他方、β−クリプトキサンチン（β-cryptoxanthine；分子量５５２）はエタノール溶解性のカロテノイドとして知られ、カンキツ類の中では温州みかんに圧倒的に多く含まれ、果実１個に１〜２ｍｇ含まれている。このβ−クリプトキサンチンは、栄養成分としてプロビタミンＡの特性を備えているだけでなく、最近の抗癌性物質の研究においては、人参等の緑黄色野菜に含有されているカロチノイドであるβ−カロチンよりも高い抗癌作用を有することが明らかになり関心を集めている（例えば、非特許文献３参照）。 On the other hand, β-cryptoxanthine (β-cryptoxanthine; molecular weight 552) is known as an ethanol-soluble carotenoid, and is predominantly contained in Citrus unshiu and 1-2 mg per fruit. This β-cryptoxanthin not only has the characteristics of provitamin A as a nutritional component, but in recent research on anticancer substances, β-carotene is a carotenoid contained in green-yellow vegetables such as carrots. It has become clear that it has a higher anti-cancer effect than that (see Non-Patent Document 3, for example).
一方、マウス骨髄細胞培養系にβ−クリプトキサンチンを添加すると様々な骨吸収因子による破骨細胞の形成をβ−クリプトキサンチンが抑制すること（例えば、非特許文献４参照。）や、積極的に骨形成を促進して骨疾患を予防・治療することができる顕著な効果を有する骨形成促進剤や、骨形成促進作用と骨吸収抑制作用の両作用を有する骨粗鬆症等の骨疾患の予防・治療薬や、骨形成促進作用と骨吸収抑制作用の両作用を有する化合物をリード化合物とする骨疾患に対する予防・治療のための有効成分のスクリーニング方法（例えば、非特許文献５参照。）、骨粗鬆症モデル動物である卵巣摘出ラットにβ−クリプトキサンチンを経口投与すると骨粗鬆症の発症が改善すること（例えば、非特許文献６参照。）が報告されている。 On the other hand, when β-cryptoxanthin is added to the mouse bone marrow cell culture system, β-cryptoxanthin suppresses the formation of osteoclasts by various bone resorption factors (see, for example, Non-Patent Document 4) or actively. Prevention and treatment of bone diseases such as osteoporosis, which has both a bone formation promoting action and a bone resorption inhibiting action, and a bone formation promoting agent that has a remarkable effect that can promote bone formation and prevent or treat bone disease A method for screening active ingredients for prevention and treatment of bone diseases using a drug or a compound having both bone formation promoting action and bone resorption inhibiting action as a lead compound (see, for example, Non-Patent Document 5), osteoporosis model It has been reported that when β-cryptoxanthin is orally administered to an ovariectomized rat, which is an animal, the onset of osteoporosis is improved (for example, see Non-patent Document 6).
このようにβ−クリプトキサンチンは発癌抑制成分として、また骨形成促進・骨吸収抑制成分として重要であることから、β−クリプトキサンチンを強化した柑橘系統や柑橘加工食品の開発に役立てるため、温州みかんに匹敵するβ−クリプトキサンチン含量の高品質柑橘類作出や、β−クリプトキサンチンを合成する遺伝子の単離（例えば、特許文献４、特許文献５参照。）や、β−クリプトキサンチンを柑橘類から大量に分離する技術の開発などが行われている。 Thus, β-cryptoxanthin is important as a carcinogenesis-inhibiting ingredient, and as an ingredient to promote bone formation and bone resorption. Therefore, in order to contribute to the development of citrus strains and processed citrus foods with enhanced β-cryptoxanthin, Production of high-quality citrus fruits with a β-cryptoxanthin content comparable to those of citrus fruits, isolation of genes that synthesize β-cryptoxanthin (see, for example, Patent Literature 4 and Patent Literature 5), and large amounts of β-cryptoxanthin from citrus fruits Development of technology for separation is underway.
また、β−クリプトキサンチンの温州みかん等の柑橘類からの分離法はよく知られており（例えば、非特許文献７、非特許文献８、非特許文献９参照。）、最近、みかん果汁を圧搾して得られた原料沈澱物等からβ−クリプトキサンチンを含有する溶剤抽出分を得、これを加水分解した後、この加水分解物を一次展開溶媒と共に平均粒子径１０〜８０μｍのシリカ粉末が充填された第１カラムに線速度２ｃｍ／分以上の流速で導入してβ−クリプトキサンチンを含むフラクションを分離し、脱溶媒した後に、この分離物を二次展開溶媒と共に平均粒子径１０〜８０μｍのオクタデシルシランシリカが充填された第二カラムに線速度２ｃｍ／分以上の流速で導入して、β−クリプトキサンチンを９５重量％以上の量で含有するフラクションを分離する高純度β−クリプトキサンチンの製造方法（例えば、特許文献６参照。）や、柑橘類の果実を搾汁、ろ過又は篩別後、遠心分離して得られる沈殿物に酵素剤を添加して凍結し、解凍した後、脱水することを特徴とするカロチノイド高含有パルプの製造方法、上記カロチノイド高含有パルプを加水して脱水する操作を繰り返した後、乾燥、粉砕するカロチノイド、β−クリプトキサンチン等の含有率が増強されたカロチノイド高含有パルプ及びその粉末の製造方法（例えば、特許文献７参照。）が提案されている。 In addition, a method for separating β-cryptoxanthin from citrus fruits such as Unshu mandarin orange is well known (see, for example, Non-Patent Document 7, Non-Patent Document 8, and Non-Patent Document 9), and recently squeezed orange juice. After obtaining the solvent extract containing β-cryptoxanthin from the obtained raw material precipitate, etc., and hydrolyzing this, the hydrolyzate is filled with silica powder having an average particle size of 10 to 80 μm together with the primary developing solvent. The fraction containing β-cryptoxanthin was introduced into the first column at a linear velocity of 2 cm / min or more, and after removing the solvent, the separated product was mixed with the secondary developing solvent to form octadecyl having an average particle size of 10 to 80 μm. A fraction containing β-cryptoxanthin in an amount of 95% by weight or more is separated by introducing into a second column packed with silane silica at a linear velocity of 2 cm / min or more. A method for producing high-purity β-cryptoxanthin (see, for example, Patent Document 6), and citrus fruits are squeezed, filtered or sieved, and then centrifuged to obtain a precipitate, which is then added with an enzyme agent and frozen. , A method for producing a carotenoid-rich pulp, which is dehydrated after being thawed, and a carotenoid, β-cryptoxanthin, and the like that are dried and pulverized after repeated operations of adding and dehydrating the above carotenoid-rich pulp A carotenoid-rich pulp with enhanced rate and a method for producing the powder thereof (for example, see Patent Document 7) have been proposed.
本発明の課題は、歯周病の予防あるいは症状改善効果を発揮しうる歯周病の予防・治療剤や、歯周病の予防・治療用の口腔用組成物を提供することにある。 An object of the present invention is to provide a periodontal disease preventive or symptom improvement periodontal disease preventive and therapeutic agent capable of exhibiting a and oral compositions for the prevention and treatment of periodontal disease.
本発明者らが確立したマウスを用いて歯周病の発症を簡便かつ迅速に評価する系を用い、マウス歯槽骨器官培養系及び歯周病モデルマウスにβ−クリプトキサンチンを適用したところ、歯周病の原因物質であるリポポリサッカライド（ＬＰＳ）による歯槽骨の破壊を抑制し、歯周病の発症を予防しうることを見い出し、本発明を完成するに至った。 Using the mouse established by the present inventors using a system for simply and rapidly evaluating the onset of periodontal disease, and applying β-cryptoxanthin to mouse alveolar bone organ culture system and periodontal disease model mice, It has been found that the destruction of alveolar bone by lipopolysaccharide (LPS), which is a causative agent of periodontal disease, can be prevented and the onset of periodontal disease can be prevented, and the present invention has been completed.
すなわち本発明は、（１）β−クリプトキサンチンを有効成分として含有する歯周病の予防・治療用の口腔用組成物に関する。
That is, this invention relates to the composition for oral cavity for the prevention and treatment of periodontal disease which contains (1) ( beta ) -cryptoxanthin as an active ingredient .
本発明の歯周病の予防・治療剤や、歯周病の予防・治療用の口腔用組成物を用いると、歯周病の予防あるいは症状改善効果を得ることができる。 When the preventive / therapeutic agent for periodontal disease or the oral composition for preventing / treating periodontal disease of the present invention is used, the effect of preventing periodontal disease or improving symptoms can be obtained.
本発明の歯周病予防・治療薬としては、β−クリプトキサンチンやβ−クリプトキサンチン含有組成物を有効成分とするものであれば特に制限されるものではなく、また、本発明の歯周病の予防・治療用の口腔用組成物としては、β−クリプトキサンチンを有効成分として含有するものであれば特に制限されるものではなく、また、歯周病の予防・治療とは、歯周病の予防あるいは症状改善効果を発揮しうることをいう。 The periodontal disease preventive / therapeutic agent of the present invention is not particularly limited as long as it contains a β-cryptoxanthin or a β-cryptoxanthin-containing composition as an active ingredient, and the periodontal disease of the present invention. the oral compositions for the prophylaxis or treatment, beta-as long as it contains cryptoxanthin as an active ingredient is not particularly limited, or, the prevention and treatment of periodontal disease, periodontal It means that it can prevent disease or improve symptoms.
β−クリプトキサンチンやβ−クリプトキサンチン含有組成物の製法としては、柑橘類から抽出・生成する方法や、β−クリプトキサンチン産生酵素をコードする遺伝子を利用する方法など公知の方法を含め特に制限されないが、その給源として、１個当たり１〜２ｍｇ含まれ、オレンジ類、グレープフルーツ、レモンなど他の柑橘類の６０倍以上のβ−クリプトキサンチンを含有する温州みかんを用いることが好ましく、温州みかんの中でも、果皮（フラベド）１００ｇ当たり約８ｍｇ、果汁１００ｇ当たり約１ｍｇのβ−クリプトキサンチンを含有する杉山温州等の高β−クリプトキサンチン含有品種の温州みかんや、温州みかんとの交配により作出された高β−クリプトキサンチン含有品種を用いることが好ましい。ここで、β−クリプトキサンチン含有組成物とは、人為的にβ−クリプトキサンチン含量が高められたβ−クリプトキサンチンの混在物をいう。また、温州みかんを処理してβ−クリプトキサンチン含有組成物を得る方法としては特に制限されず、例えば、前述の特許文献６、７の他、非特許文献７〜９に記載の処理方法を挙げることができる。 The method for producing β-cryptoxanthin and β-cryptoxanthin-containing compositions is not particularly limited, including known methods such as a method of extracting and generating from citrus fruits, and a method of using a gene encoding a β-cryptoxanthin producing enzyme. As the supply source, it is preferable to use Unshu mandarin, which contains 1 to 2 mg per piece, and contains β-cryptoxanthin more than 60 times that of other citrus fruits such as oranges, grapefruits and lemons. (Flaved) About 8 mg per 100 g and about 1 mg of β-cryptoxanthin per 100 g of fruit juice Sugiyama Wenzhou and other high β-cryptoxanthin-containing varieties Wenzhou mandarin and high β-crypt produced by crossing with Wenzhou It is preferable to use a xanthine-containing variety. Here, the β-cryptoxanthin-containing composition refers to a mixture of β-cryptoxanthin in which the β-cryptoxanthin content is artificially increased. Moreover, it does not restrict | limit especially as a method of processing a Satsuma mandarin and obtaining a beta-cryptoxanthin containing composition, For example, the processing method of nonpatent literature 7-9 other than the above-mentioned patent documents 6 and 7 is mentioned. be able to.
本発明の歯周病の予防・治療剤には、消炎・抗炎症薬や植物からの抽出物を併用することもできる。上記鎮痛・消炎・抗炎症薬としては、イブプロフェンピコノール、インドメタシン、ウフェナマート、ケトプロフェン、グリチルレチン酸、ジクロフェナクナトリウム、スプロフェン、ピロキシカム、フェルビナク、ブフェキサマク、フルルビプロフェン、ペンダザック、ジフェンヒドラミン、ラウリル硫酸ジフェンヒドラミン、アムシノニド、吉草酸酢酸プレドニゾロン、吉草酸ジフルコルトロン、吉草酸デキサメタゾン、吉草酸ベタメタゾン、酢酸ジフロラゾン、酢酸ヒドロコルチゾン、ジフルプレドナート、ジプロピオン酸ベタメタゾン、デキサメタゾン、トリアムシノロンアセトニド、ハルシノニド、ピバル酸フルメタゾン、フランカルボン酸モメタゾン、フルオシノニド、フルオシノロンアセトニド、フルドロキシコルチド、プレドニゾロン、プロピオン酸アルクロメタゾン、プロピオン酸クロベタゾール、プロピオン酸デキサメタゾン、プロピオン酸デプロドン、プロピオン酸ベクロメタゾン、酪酸クロベタゾン、酪酸ヒドロコルチゾン、酪酸プロピオン酸ヒドロコルチゾン、酪酸プロピオン酸ベタメタゾン、酢酸プレドニゾロンなどを挙げることができる。また、候補薬剤としての上記抗生物質としては、塩酸オキシテトラサイクリン、塩酸テトラサイクリン、ゲンタマイシン、フラジオマイシン、エリスロマイシン、ピマリシン、硫酸ブレオマイシン、合成ペニシリン、合成セファロスポリン、バンコマイシンなどを挙げることができる。さらに、植物からの抽出物としては、柑橘類由来のポリメトキシフラボノイド類であるノビレチン、タンゲレチン、ナリルチン、シネンセチンなどを挙げることができ、またこれらのポリメトキシフラボノイドに代えて、シークヮーサーエキスなどのポリメトキシフラボノイド類を含む柑橘類由来のエキス類を用いることもできる。 In the preventive / therapeutic agent for periodontal disease of the present invention, an anti-inflammatory / anti-inflammatory drug or an extract from a plant can be used in combination. Examples of the analgesic / anti-inflammatory / anti-inflammatory drugs include ibuprofen piconol, indomethacin, ufenamate, ketoprofen, glycyrrhetinic acid, diclofenac sodium, suprofen, piroxicam, felbinac, bufexamac, flurbiprofen, pendazac, diphenhydramine, diphenhydramine lauryl sulfate, Prednisolone valerate acetate, diflucortron valerate, dexamethasone valerate, betamethasone valerate, diflorazone acetate, hydrocortisone acetate, diflupredonate, betamethasone dipropionate, dexamethasone, triamcinolone acetonide, halsinonide, flumetasone pivalate, mometasone furanate , Fluocinonide, fluocinolone acetonide, fludroxycortide, pre Nizoron, alclometasone propionate, clobetasol propionate, can be given dexamethasone propionate, deprodone propionate, beclomethasone propionate, clobetasone butyrate, hydrocortisone butyrate, butyrate propionate, hydrocortisone, betamethasone butyrate propionate, acetate and the like prednisolone. Examples of the antibiotics as candidate drugs include oxytetracycline hydrochloride, tetracycline hydrochloride, gentamicin, fradiomycin, erythromycin, pimaricin, bleomycin sulfate, synthetic penicillin, synthetic cephalosporin, vancomycin and the like. Furthermore, examples of plant extracts include citrus-derived polymethoxyflavonoids such as nobiletin, tangeretin, nariltin, and synencetin. In addition to these polymethoxyflavonoids, polymethoxyflavonoids such as seeker extract Extracts derived from citrus fruits including citrus can also be used.
本発明の歯周病の予防・治療剤を、医薬用の治療剤として経口的に用いる場合は、薬学的に許容される通常の担体、結合剤、安定化剤、賦形剤、希釈剤、ｐＨ緩衝剤、崩壊剤、可溶化剤、溶解補助剤、等張剤などの各種調剤用配合成分や、香料、甘味剤、風味調味料等の成分を添加することができ、化粧料・塗布薬等として経皮的に用いる場合は、保湿剤、界面活性剤、防腐・殺菌・抗菌剤、油分、アルコール類、酸化防止剤、増粘剤、キレート剤、ｐＨ調整剤、ビタミン類、アミノ酸類、香料、色素、水等、血行促進剤などの各種配合成分を添加することができる。例えば、粉末、顆粒、錠剤、カプセル剤、シロップ剤、懸濁液、ドリンク剤等の剤型で経口的に投与することができ、また、軟膏、クリーム、乳液、ローション、パック、リップ、入浴剤、ヘアートニック、ヘアーローション、石鹸、ボディシャンプー等の剤型で経皮的に投与することができる。 Periodontal disease preventive and therapeutic agent of the present invention, when used as a pharmaceutical therapeutic agent orally, the usual carriers, binders pharmaceutically acceptable stabilizing agents, excipients, diluents Ingredients for various preparations such as agents, pH buffering agents, disintegrants, solubilizers, solubilizers, isotonic agents, and ingredients such as fragrances, sweeteners, flavor seasonings can be added. Moisturizer, surfactant, antiseptic / bactericidal / antibacterial agent, oil, alcohol, antioxidant, thickener, chelating agent, pH adjuster, vitamins, amino acids Various blending components such as scents, perfumes, pigments, water, and blood circulation promoters can be added. For example, it can be administered orally in dosage forms such as powders, granules, tablets, capsules, syrups, suspensions, drinks, and ointments, creams, emulsions, lotions, packs, lips, baths It can be administered transdermally in dosage forms such as hair nick, hair lotion, soap, body shampoo.
本発明の歯周病の予防・治療用の口腔用組成物は、歯磨き、口腔内軟膏剤、口中洗浄剤等として使用することができ、β−クリプトキサンチン以外にも通常の口腔用組成物に配合される成分を配合することができる。例えば、湿潤剤、防腐剤、研磨剤、粘稠剤、粘結剤、甘味剤、界面活性剤、香味剤、保存剤、着色剤、ｐＨ調整剤、賦形剤、酵素剤等を適宜に配合することができる。なお、歯周病の予防・治療用とは、歯磨きや口中洗浄剤の包装容器や説明書等に、歯周病の予防や治療に有効である旨表示されている場合などを意味する。 The composition for oral cavity for the prevention and treatment of periodontal disease of the present invention can be used as a toothpaste, an oral ointment, a mouth rinse, etc., and in addition to β-cryptoxanthin, Components to be blended can be blended. For example, wetting agents, preservatives, abrasives, thickeners, binders, sweeteners, surfactants, flavoring agents, preservatives, colorants, pH adjusters, excipients, enzyme agents, etc. can do. The term "for prevention / treatment of periodontal disease" means a case where it is indicated that it is effective for prevention or treatment of periodontal disease on a toothbrush or a packaging container for a mouth rinse or a manual.
以下、実施例により本発明をより具体的に説明するが、本発明の技術的範囲はこれらの例示に限定されるものではない。 EXAMPLES Hereinafter, although an Example demonstrates this invention more concretely, the technical scope of this invention is not limited to these illustrations.
（β−クリプトキサンチンによる歯槽骨破壊の改善）
６週齢のｄｄｙ系マウスより下顎を採取し、実体顕微鏡下において、臼歯及び切歯を抜歯したものを歯槽骨とした。４８ウェルプレートを用い、１ｍｇ／ｍｌＢＳＡ含有のＢＧＪｂ（ペニシリン６３．２ｍｇ／ｌ及びストレプトマイシン１００ｍｇ／ｌ含有）培養液２００μｌにて３７℃で２４時間培養した。その後、上記１ｍｇ／ｍｌＢＳＡ含有のＢＧＪｂ培養液２００μｌにＬＰＳ（１０μｇ／ｍｌ；Ｓｉｇｍａ社製）を単独添加し、あるいは、ＬＰＳ（１０μｇ／ｍｌ）及びβ−クリプトキサンチン（２．５μＭ）を併用添加し、培養４日目における培養上清中のＣａ濃度を、カルシウムＣテストワコー（和光社製）により測定した（ｎ＝４）。また、上記１ｍｇ／ｍｌＢＳＡ含有ＢＧＪｂ培養液２００μｌに、ＬＰＳとβ−クリプトキサンチンを添加しない場合を対照（Control）とした。結果を図１に示す。
(Improvement of alveolar bone destruction by β-cryptoxanthin)
The lower jaw was collected from a 6-week-old ddy mouse, and the molar and incisor extracted under a stereomicroscope were used as alveolar bone. Using a 48-well plate, 1 mg / ml BSA-containing BGJb (containing penicillin 63.2 mg / l and streptomycin 100 mg / l) culture was cultured at 37 ° C. for 24 hours. Thereafter, LPS (10 μg / ml; manufactured by Sigma) is added alone to 200 μl of the BGJb culture solution containing 1 mg / ml BSA, or LPS (10 μg / ml) and β-cryptoxanthin (2.5 μM) are added in combination. The Ca concentration in the culture supernatant on the 4th day of culture was measured with Calcium C Test Wako (Wako) (n = 4). Moreover, the case where LPS and β-cryptoxanthin were not added to 200 μl of the above 1 mg / ml BSA-containing BGJb culture solution was used as a control. The results are shown in FIG.
本実験の結果、処理後４日目、ＬＰＳ添加によって歯槽骨の破壊が進み骨吸収活性の上昇が認められたが、β−クリプトキサンチン併用添加により骨吸収活性が有意に抑制された（図１中、＊；Ｐ＜０．０１ ｖｓ Control、＃；Ｐ＜０．０５ ｖｓ ＬＰＳ）。すなわち、歯槽骨器官培養系において、β−クリプトキサンチンは歯周病の原因物質であるＬＰＳによる歯槽骨の破壊を予防した。 As a result of this experiment, on the 4th day after the treatment, alveolar bone destruction progressed and the increase of bone resorption activity was observed by addition of LPS, but the bone resorption activity was significantly suppressed by the combined use of β-cryptoxanthin (FIG. 1). *, P <0.01 vs Control, #; P <0.05 vs LPS). That is, in the alveolar bone organ culture system, β-cryptoxanthin prevented the destruction of alveolar bone by LPS, which is a causative agent of periodontal disease.
（β−クリプトキサンチンによる歯周病の予防）
６週齢のｄｄｙ系マウスの下顎臼歯外側の歯肉に溶媒（ＤＭＳＯ／ＰＥＧ３００ １：４）を投与したマウスを対照（Control）群、ＬＰＳ（５０μｇ／ｂｏｄｙ／ｄａｙ）を投与したマウスをＬＰＳ群、ＬＰＳ（５０μｇ／ｂｏｄｙ／ｄａｙ）及びβ−クリプトキサンチン（１２μｇ／ｂｏｄｙ／ｄａｙ）を混合した液を投与したマウスを併用投与群、β−クリプトキサンチンのみを投与したマウスをβ−クリプトキサンチン群として、１日おきにマウスに３回投与した。３回目投与の３日後に歯槽骨を摘出し、抜歯の後、ＤＥＸＡ（dual energy X-ray absorptiometry：Ａｌｏｋａ社製）法により歯槽骨の骨密度（ＢＭＤ）を測定した（ｎ＝４）。結果を図２に示す。
(Prevention of periodontal disease by β-cryptoxanthin)
Mice administered solvent (DMSO / PEG300 1: 4) to the gingiva of the lower molars of 6-week-old ddy mice were given control (control) group, and mice given LPS (50 μg / body / day) were LPS group, Mice administered with a mixture of LPS (50 μg / body / day) and β-cryptoxanthin (12 μg / body / day) combined administration group, mice administered with β-cryptoxanthin only as β-cryptoxanthin group, Mice were administered 3 times every other day. Three days after the third administration, the alveolar bone was extracted, and after extraction, the bone density (BMD) of the alveolar bone was measured by the DEXA (dual energy X-ray absorptiometry: Aloka) method (n = 4). The results are shown in FIG.
本実験の結果、ＬＰＳ投与により誘導された歯周病モデルマウスにおける歯槽骨の密度低下はβ−クリプトキサンチンの併用投与により予防された（図２中、＊；Ｐ＜０．０５ｖｓ Control、＃；Ｐ＜０．０５ ｖｓ ＬＰＳ）。以上よりβ−クリプトキサンチンが歯周病の予防に有効性を示すことが明らかとなった。 As a result of this experiment, the decrease in alveolar bone density in periodontal disease model mice induced by LPS administration was prevented by the combined administration of β-cryptoxanthin (in FIG. 2, *; P <0.05 vs Control, #; P <0.05 vs LPS). From the above, it was revealed that β-cryptoxanthin is effective in preventing periodontal disease.
Claims (1)
An oral composition for the prevention and treatment of periodontal disease containing β-cryptoxanthin as an active ingredient.
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