JP2021100975A - Agent for periodontal tissue regeneration, method for periodontal tissue regeneration, agent for periodontal tissue proliferation and activation, and antiaging agent for periodontium - Google Patents
Agent for periodontal tissue regeneration, method for periodontal tissue regeneration, agent for periodontal tissue proliferation and activation, and antiaging agent for periodontium Download PDFInfo
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- JP2021100975A JP2021100975A JP2021062793A JP2021062793A JP2021100975A JP 2021100975 A JP2021100975 A JP 2021100975A JP 2021062793 A JP2021062793 A JP 2021062793A JP 2021062793 A JP2021062793 A JP 2021062793A JP 2021100975 A JP2021100975 A JP 2021100975A
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- periodontal tissue
- periodontal
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- extract
- tissue regeneration
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
Description
本発明は、歯周組織再生剤、歯周組織再生方法、歯周組織増殖・活性化剤及び歯周組織アンチエージング剤に関する。 The present invention relates to a periodontal tissue regeneration agent, a periodontal tissue regeneration method, a periodontal tissue growth / activator, and a periodontal tissue anti-aging agent.
歯周病を患うと歯周組織の崩壊が生じ、歯のぐらつきや口臭といったＱＯＬの低下が起こる。また、生活習慣や加齢により歯肉（歯茎）の後退（退縮）が起こることも知られている。上記歯周組織は歯肉（歯茎）と歯槽骨（歯を支える骨組織）、歯根（歯の根元）を覆うセメント質、歯根と歯槽骨をつなぐ歯根膜等からなり、歯を正しい位置にしっかり付着固定するための強固な構造を備えている。しかし、いろいろな理由で歯と歯肉の間に細菌が住み着いて歯垢（デンタルプラーク）がたまると、そこに炎症が引き起こされる。これが歯周病の始まりとなる。歯周病の治療は病状によるが、上記炎症が歯茎の奥深くまで進行し、歯周組織の破壊がひどい場合には、歯周組織を回復させるための歯周組織再生手術が必要となる。この歯周組織再生手術では、歯周組織が破壊されて空洞となった部分に人工の膜を挿入する必要がある。 When suffering from periodontal disease, periodontal tissue collapses, resulting in a decrease in QOL such as tooth wobbling and bad breath. It is also known that the gingiva (gingiva) recedes (regresses) due to lifestyle and aging. The periodontal tissue consists of gingiva (gingiva) and alveolar bone (bone tissue that supports the tooth), cementum that covers the tooth root (root of the tooth), periodontal ligament that connects the tooth root and alveolar bone, etc., and firmly adheres the tooth to the correct position. It has a strong structure for fixing. However, when bacteria settle between the teeth and gums for various reasons and plaque (dental plaque) accumulates there, inflammation is caused there. This is the beginning of periodontal disease. Treatment of periodontal disease depends on the medical condition, but if the inflammation progresses deep into the gums and the periodontal tissue is severely destroyed, periodontal tissue regeneration surgery is required to restore the periodontal tissue. In this periodontal tissue regeneration surgery, it is necessary to insert an artificial membrane into the portion where the periodontal tissue is destroyed and becomes hollow.
一方、歯のエナメル質を形成する作用のあるエナメルタンパク質調製物が、歯周組織の誘導・再生にも関わっていることから、このエナメルタンパク質調製物を歯周病治療における歯根膜再生のために使うことが臨床的に行われている。しかし、実際の治療時に歯根膜再生が必ずしも期待されるレベルの結果に達しないケースも少なくないこと、エナメルタンパク質調製物としては、ブタの幼若エナメル質基質からの抽出物が使われるため、未同定ウイルス感染の危険性も指摘されている等の不都合がある。また、上記エナメルタンパク質調製物の一成分であるシースリンタンパクや、それに由来するペプチドに歯周組織再生作用があることが知られている（特開２０１１−２２５５１９号公報参照）。また、インスリン様成長因子−1及びトランスフォーミング成長因子−β１を有効成分として含む組織再生用組成物も知られている（特開２０１４−１５６４１０号公報参照）。しかし、これらの物質の歯周組織再生作用は十分とは言えず、またタンパクやペプチド性の物質であるため動物由来成分の混入等の可能性も指摘され、人に対して用いる場合には安全性面で注意を要する。 On the other hand, since the enamel protein preparation that has the effect of forming tooth enamel is also involved in the induction and regeneration of periodontal tissue, this enamel protein preparation is used for periodontal ligament regeneration in the treatment of periodontal disease. It is clinically used. However, there are many cases in which periodontal ligament regeneration does not always reach the expected level of results during actual treatment, and as the enamel protein preparation, an extract from porcine immature enamel substrate is used, so it has not been achieved. There are inconveniences such as the risk of identification virus infection being pointed out. Further, it is known that the sheath phosphorus protein, which is one component of the above enamel protein preparation, and a peptide derived from the sheath phosphorus protein have a periodontal tissue regeneration action (see Japanese Patent Application Laid-Open No. 2011-225519). Further, a composition for tissue regeneration containing insulin-like growth factor-1 and transforming growth factor-β1 as active ingredients is also known (see JP-A-2014-156410). However, the periodontal tissue regeneration action of these substances is not sufficient, and since they are protein and peptide substances, the possibility of contamination with animal-derived components has been pointed out, and they are safe when used for humans. Be careful about sexuality.
本発明は、上述のような状況の中、手術等を要することなく、より効果的に且つ安全に歯周組織の再生を促す歯周組織再生剤、この歯周組織再生剤を用いた歯周組織再生方法、歯周組織増殖・活性化剤及び歯周組織アンチエージング剤を提供することを目的とする。 The present invention is a periodontium regenerating agent that promotes periodontium regeneration more effectively and safely without requiring surgery or the like under the above-mentioned circumstances, and a periodontium using this periodontium regenerating agent. An object of the present invention is to provide a method for tissue regeneration, a periodontium growth / activator, and a periodontium anti-aging agent.
上記課題を解決するために、本発明者が種々検討した結果、従来、保湿作用、美白作用、増粘作用、抗菌作用、抗ウイルス作用等を有する成分として知られており、歯周組織の再生とは何ら無縁であった物質の中に、優れた歯周組織再生能を有するものがあることを初めて見出した。歯周組織とは、歯の周辺組織であり、歯根膜、歯槽骨、歯肉（歯茎）、セメント質、細胞外マトリックスを意味する。本願発明の歯周組織再生剤等は、これらの歯周組織を再生等させるものである。すなわち本発明の要旨は、以下の通りである。 As a result of various studies by the present inventor in order to solve the above problems, it has been conventionally known as a component having a moisturizing effect, a whitening effect, a thickening effect, an antibacterial effect, an antiviral effect, and the like, and regenerates periodontium. For the first time, we found that some substances that had nothing to do with the periodontium had excellent periodontal tissue regeneration ability. Periodontal tissue is the tissue surrounding the tooth and means periodontal ligament, alveolar bone, gingiva (gingiva), cementum, and extracellular matrix. The periodontal tissue regenerating agent and the like of the present invention regenerate these periodontal tissues. That is, the gist of the present invention is as follows.
＜１＞ハッカ油、ユリエキス、真珠タンパク質エキス、アロエエキス、グリチルリチン酸二カリウム、カンゾウエキス、イソ吉草酸イソアミル、ウイキョウ油、クエン酸ナトリウム、Ｌ−グルタミン酸塩酸塩、セバシン酸ジエチル、チモール、濃グリセリン、ハチミツ、ヘスペリジン、ペパーミントエッセンス、ベンジルアルコール、Ｄ−マンニトール、メチルセルロース、及びカルバゾクロムからなる群より選択される少なくとも一種を含有する、歯周組織再生剤。 <1> Peppermint oil, lily extract, pearl protein extract, aloe extract, dipotassium glycyrrhizinate, licorice extract, isoamyl isovalerate, syrup oil, sodium citrate, L-glutamate, diethyl sebacate, timol, concentrated glycerin, A periodontal tissue regenerating agent containing at least one selected from the group consisting of honey, hesperidin, peppermint essence, benzyl alcohol, D-mannitol, methyl cellulose, and carbazochrome.
＜２＞上記歯周組織が、歯茎及び／又は歯根膜である、＜１＞記載の歯周組織再生剤。 <2> The periodontal tissue regenerating agent according to <1>, wherein the periodontal tissue is the gum and / or periodontal ligament.
＜３＞上記歯周組織が、歯根膜である、＜１＞又は＜２＞記載の歯周組織再生剤。 <3> The periodontal tissue regenerating agent according to <1> or <2>, wherein the periodontal tissue is periodontal ligament.
＜４＞歯周組織の修復のために用いられる、＜１＞〜＜３＞のいずれか記載の歯周組織再生剤。 <4> The periodontal tissue regenerating agent according to any one of <1> to <3>, which is used for repairing periodontal tissue.
＜５＞歯周病の治療のために用いられる、＜１＞〜＜４＞のいずれか記載の歯周組織再生剤。 <5> The periodontal tissue regenerating agent according to any one of <1> to <4>, which is used for the treatment of periodontal disease.
＜６＞歯周病により崩壊した歯根膜の治療のために用いられる、＜５＞記載の歯周組織再生剤。 <6> The periodontal tissue regenerating agent according to <5>, which is used for treating periodontal ligament that has collapsed due to periodontal disease.
＜７＞＜１＞〜＜６＞のいずれか記載の歯周組織再生剤を含有する、口腔用組成物。 <7> An oral composition containing the periodontal tissue regenerating agent according to any one of <1> to <6>.
＜８＞＜１＞〜＜６＞のいずれか記載の歯周組織再生剤を含有する、歯周組織再生キット。 <8> A periodontal tissue regeneration kit containing the periodontal tissue regeneration agent according to any one of <1> to <6>.
＜９＞＜１＞〜＜６＞のいずれか記載の歯周組織再生剤を含有する、細胞培養用培地。 <9> A cell culture medium containing the periodontal tissue regenerating agent according to any one of <1> to <6>.
＜１０＞＜１＞〜＜６＞のいずれか記載の歯周組織再生剤を用いる、歯周組織再生方法。 <10> A method for regenerating periodontal tissue using the periodontal tissue regenerating agent according to any one of <1> to <6>.
＜１１＞ハッカ油、ユリエキス、真珠タンパク質エキス、アロエエキス、グリチルリチン酸二カリウム、カンゾウエキス、イソ吉草酸イソアミル、ウイキョウ油、クエン酸ナトリウム、Ｌ−グルタミン酸塩酸塩、セバシン酸ジエチル、チモール、濃グリセリン、ハチミツ、ヘスペリジン、ペパーミントエッセンス、ベンジルアルコール、Ｄ−マンニトール、メチルセルロース、及びカルバゾクロムからなる群より選択される少なくとも一種を含有する、歯周組織増殖・活性化剤。 <11> Peppermint oil, lily extract, pearl protein extract, aloe extract, dipotassium glycyrrhizinate, licorice extract, isoamyl isovalerate, syrup oil, sodium citrate, L-glutamate, diethyl sebacate, timol, concentrated glycerin, A periodontal tissue growth / activator containing at least one selected from the group consisting of honey, hesperidin, peppermint essence, benzyl alcohol, D-mannitol, methyl cellulose, and carbazochrome.
＜１２＞ハッカ油、ユリエキス、真珠タンパク質エキス、アロエエキス、グリチルリチン酸二カリウム、カンゾウエキス、イソ吉草酸イソアミル、ウイキョウ油、クエン酸ナトリウム、Ｌ−グルタミン酸塩酸塩、セバシン酸ジエチル、チモール、濃グリセリン、ハチミツ、ヘスペリジン、ペパーミントエッセンス、ベンジルアルコール、Ｄ−マンニトール、メチルセルロース、及びカルバゾクロムからなる群より選択される少なくとも一種を含有する、歯周組織アンチエージング剤。 <12> Peppermint oil, lily extract, pearl protein extract, aloe extract, dipotassium glycyrrhizinate, licorice extract, isoamyl isovalerate, syrup oil, sodium citrate, L-glutamate, diethyl sebacate, timol, concentrated glycerin, A periodontal tissue anti-aging agent containing at least one selected from the group consisting of honey, hesperidin, peppermint essence, benzyl alcohol, D-mannitol, methyl cellulose, and carbazochrome.
＜１３＞ハッカ油、ユリエキス、真珠タンパク質エキス、アロエエキス、グリチルリチン酸二カリウム、カンゾウエキス、イソ吉草酸イソアミル、ウイキョウ油、クエン酸ナトリウム、Ｌ−グルタミン酸塩酸塩、セバシン酸ジエチル、チモール、濃グリセリン、ハチミツ、ヘスペリジン、ペパーミントエッセンス、ベンジルアルコール、Ｄ−マンニトール、メチルセルロース、及びカルバゾクロムからなる群より選択される少なくとも一種を含有する、歯根膜再生剤。 <13> Peppermint oil, lily extract, pearl protein extract, aloe extract, dipotassium glycyrrhizinate, licorice extract, isoamyl isovalerate, syrup oil, sodium citrate, L-glutamate, diethyl sebacate, timol, concentrated glycerin, A root membrane regenerating agent containing at least one selected from the group consisting of honey, hesperidin, peppermint essence, benzyl alcohol, D-mannitol, methyl cellulose, and carbazochrome.
＜１４＞ハッカ油、ユリエキス、真珠タンパク質エキス、アロエエキス、グリチルリチン酸二カリウム、カンゾウエキス、イソ吉草酸イソアミル、ウイキョウ油、クエン酸ナトリウム、Ｌ−グルタミン酸塩酸塩、セバシン酸ジエチル、チモール、濃グリセリン、ハチミツ、ヘスペリジン、ペパーミントエッセンス、ベンジルアルコール、Ｄ−マンニトール、メチルセルロース、及びカルバゾクロムからなる群より選択される少なくとも一種を含有する、歯根膜修復剤。 <14> Peppermint oil, lily extract, pearl protein extract, aloe extract, dipotassium glycyrrhizinate, licorice extract, isoamyl isovalerate, syrup oil, sodium citrate, L-glutamate, diethyl sebacate, timol, concentrated glycerin, A root membrane repair agent containing at least one selected from the group consisting of honey, hesperidin, peppermint essence, benzyl alcohol, D-mannitol, methyl cellulose, and carbazochrome.
＜１５＞ハッカ油、ユリエキス、真珠タンパク質エキス、アロエエキス、グリチルリチン酸二カリウム、カンゾウエキス、イソ吉草酸イソアミル、ウイキョウ油、クエン酸ナトリウム、Ｌ−グルタミン酸塩酸塩、セバシン酸ジエチル、チモール、濃グリセリン、ハチミツ、ヘスペリジン、ペパーミントエッセンス、ベンジルアルコール、Ｄ−マンニトール、メチルセルロース、及びカルバゾクロムからなる群より選択される少なくとも一種を含有し、歯周病により崩壊した歯根膜の再生・修復のために用いられる、歯周病の治療及び／又は改善剤。 <15> Peppermint oil, lily extract, pearl protein extract, aloe extract, dipotassium glycyrrhizinate, citrus extract, isoamyl isovalerate, oyster oil, sodium citrate, L-glutamate salt, diethyl sebacate, timol, concentrated glycerin, A tooth containing at least one selected from the group consisting of honey, hesperidin, peppermint essence, benzyl alcohol, D-mannitol, methyl cellulose, and carbazochrome, and used for regeneration and restoration of root membrane collapsed due to periodontal disease. Treatment and / or ameliorating agent for periodontal disease.
本発明の歯周組織再生剤によると、歯周病や事故等により崩壊した歯根膜を効果的に再生し、手術等を要することなく歯周組織を修復することができる。また、本発明の歯周組織再生剤等は、歯根膜、歯茎等の歯周組織を再生・修復することによって、歯周病等で崩壊した歯周組織を蘇らせる、修繕する、補修する、復活させる、蘇生させる、復元させる、生まれ変わらせる、健康な状態に向けて回復させる、又は治癒させる等の効果を奏する。さらに、本発明の歯周組織再生剤等が有効成分として含む成分は、すでに安全性が確認された成分であるため、人に対して安心して使用することができ、特に日常的な使用に好適である。 According to the periodontal tissue regenerating agent of the present invention, the periodontal ligament collapsed due to periodontal disease, accident, or the like can be effectively regenerated, and the periodontal tissue can be repaired without requiring surgery or the like. Further, the periodontal tissue regenerating agent or the like of the present invention regenerates, repairs, or repairs periodontal tissue that has collapsed due to periodontal disease or the like by regenerating and repairing periodontal tissue such as periodontal ligament and gum. It has the effects of reviving, reviving, restoring, reborn, recovering to a healthy state, or healing. Furthermore, since the component contained in the periodontal tissue regenerating agent or the like of the present invention as an active ingredient has already been confirmed to be safe, it can be safely used by humans and is particularly suitable for daily use. Is.
以下、本発明について詳細に説明する。 Hereinafter, the present invention will be described in detail.
［歯周組織再生剤］
本発明の歯周組織再生剤は、植物抽出エキス、グルタミン酸（Ｌ−グルタミン酸塩酸塩）等の植物由来成分、真珠タンパク質エキス等の動物性成分、Ｄ−マンニトール、濃グリセリン、ベンジルアルコール等の1つ以上の水酸基を有するアルコール類（糖アルコール、芳香族アルコール、多価アルコール）、クエン酸ナトリウム等のｐＨ調整剤、及びカルバゾクロム等の止血剤からなる群より選択される少なくとも１種を有効成分として含む。本発明の歯周組織再生剤は、これらのいずれかを歯周組織再生のための有効成分として含むことで、歯根膜を再生させ、歯周病等により崩壊した歯周組織を再生及び／又は修復することができる。また、本発明の歯周組織再生剤は、歯根膜、歯茎等の歯周組織を再生・修復することによって、歯周病等で崩壊した歯周組織を蘇らせる、修繕する、補修する、復活させる、蘇生させる、復元させる、生まれ変わらせる、健康な状態に向けて回復させる、又は治癒させる等の効果を奏することができる。本発明の歯周組織再生剤は、上記有効成分以外に、本発明の効果を損なわない範囲で、他の任意成分を含んでいてもよい。以下、それぞれの成分について説明する。なお、本発明の歯周組織再生剤は、歯周組織、即ち、歯根膜、歯槽骨、歯肉（歯茎）、セメント質、細胞外マトリックスのいずれかを再生及び／又は修復するという効果を有するものである。本発明の歯周組織再生剤は、歯茎、歯根膜の再生作用に特に優れ、その他の歯周組織については再生作用を有するか、又は歯茎、歯根膜の再生に引き続き起こる二次的な再生作用を有するものである。即ち、歯茎、歯根膜細胞の再生に引き続き起こる細胞外マトリックスの形成等も広く歯周組織再生作用に含まれる。また、本発明の歯周組織再生剤は、特に歯根膜再生剤、歯根膜修復剤、歯根膜・歯茎等の歯周組織を再生・修復するための歯周病の治療及び／又は改善剤としても用いることができる。
[Periodontal tissue regeneration agent]
The periodontal tissue regenerating agent of the present invention is one of a plant extract, a plant-derived component such as glutamic acid (L-glutamate salt salt), an animal component such as a pearl protein extract, D-mannitol, concentrated glycerin, and benzyl alcohol. The active ingredient contains at least one selected from the group consisting of alcohols having the above hydroxyl groups (sugar alcohols, aromatic alcohols, polyhydric alcohols), pH adjusters such as sodium citrate, and hemostatic agents such as carbazochrome. .. The periodontal tissue regenerating agent of the present invention contains any of these as an active ingredient for periodontal tissue regeneration to regenerate the periodontal ligament and regenerate and / or regenerate the periodontal tissue disintegrated due to periodontal disease or the like. Can be repaired. In addition, the periodontal tissue regenerating agent of the present invention regenerates, repairs, repairs, and restores periodontal tissue that has collapsed due to periodontal disease, etc. by regenerating and repairing periodontal tissues such as periodontal ligament and gums. It can exert effects such as rejuvenating, reviving, restoring, reborn, recovering to a healthy state, or healing. The periodontal tissue regenerating agent of the present invention may contain other optional ingredients in addition to the above active ingredients as long as the effects of the present invention are not impaired. Hereinafter, each component will be described. The periodontal tissue regenerating agent of the present invention has the effect of regenerating and / or repairing any of the periodontal ligament, that is, periodontal ligament, alveolar bone, gingiva (gingiva), cementum, and extracellular matrix. Is. The periodontal tissue regenerating agent of the present invention is particularly excellent in the regenerating action of the gingiva and periodontal ligament, has a regenerating action for other periodontal tissues, or has a secondary regenerating action following the regeneration of the gingiva and periodontal ligament. It has. That is, the formation of extracellular matrix following the regeneration of gum and periodontal ligament cells is also widely included in the periodontal tissue regeneration action. Further, the periodontal tissue regenerating agent of the present invention is particularly used as a periodontal disease regenerating agent, a periodontal ligament restoration agent, and a treatment and / or ameliorating agent for periodontal disease for regenerating and repairing periodontal tissues such as periodontal ligament and gum. Can also be used.
（植物由来成分）
本発明の歯周組織再生剤が含む植物由来成分としては、例えば、ウイキョウ油（製造元：山本香料、司生堂製薬、小川香料など）、ハッカ油（製造元：長岡香料、高砂香料、小城製薬、東洋薄荷工業、もしくは日局のもの）、ペパーミントエッセンス（製造元：高砂香料、池田物産など）、カンゾウエキス（抽出方法を限定するものではないが、好ましくはエタノール抽出）、アロエエキス（抽出方法を限定するものではないが、好ましくはエタノール抽出）、ユリエキス（抽出方法を限定するものではないが、好ましくはブチレングリコール抽出）等の植物抽出エキス；イソ吉草酸イソアミル（製造元：井上香料）、チモール（製造元：大阪化成）、ヘスペリジン（製造元：アルプス薬品工業）、グリチルリチン酸二カリウム（製造元：アルプス薬品工業、丸善製薬など）、セバシン酸ジエチル（製造元：日光ケミカルズ、日本精化など）、ハチミツ（製造元：一丸ファルコス、小城製薬、塩野香料、小堺製薬、丸石製薬、日研化成、純正化学など）、メチルセルロース（製造元：信越化学工業）等、グルタミン酸（Ｌ−グルタミン酸塩酸塩）（製造元：協和発酵、味の素、日理科学、旭化成ケミカルズなど）等の植物含有成分が挙げられる。ここで、本明細書において植物由来成分とは、植物から抽出されるエキス、植物から分離・精製される成分、又はこれらを原料として生成される成分のことをいう。
(Plant-derived ingredients)
Examples of plant-derived components contained in the periodontal tissue regenerating agent of the present invention include mint oil (manufacturer: Yamamoto fragrance, Shiseido Pharmaceutical, Ogawa fragrance, etc.), mint oil (manufacturer: Nagaoka fragrance, Takasago fragrance, Koshiro Pharmaceutical, etc.) Toyo Lightweight Industry or Japan Bureau), Peppermint Essence (Manufacturer: Takasago Fragrance, Ikeda Bussan, etc.), Kanzo Extract (Extracting method is not limited, but preferably ethanol extraction), Aloe Extract (Extracting method is limited) Plant extracts such as but not limited to ethanol extraction, preferably lily extract (preferably butylene glycol extraction, although the extraction method is not limited); isoamyl isovalerate (manufacturer: Inoue fragrance), Timor (manufacturer) : Osaka Kasei), Hesperidin (Manufacturer: Alps Pharmaceutical Industry), Dipotassium glycyrrhizinate (Manufacturer: Alps Pharmaceutical Industry, Maruzen Pharmaceutical Co., Ltd.), Diethyl sebacate (Manufacturer: Nikko Chemicals, Nippon Seika, etc.), Honey (Manufacturer: Ichimaru) Falcos, Koshiro Pharmaceutical, Shiono Fragrance, Kosakai Pharmaceutical, Maruishi Pharmaceutical, Nikken Kasei, Genuine Chemical, etc.), Methylcellulose (Manufacturer: Shinetsu Chemical Industry), etc., Glutamic acid (L-glutamate) (Manufacturer: Kyowa Hakko, Ajinomoto, Nihon Plant-containing components such as physics and science, Asahi Kasei Chemicals, etc.). Here, the plant-derived component as used herein refers to an extract extracted from a plant, a component separated / purified from a plant, or a component produced from these as a raw material.
これらのうち、歯周組織再生能に優れる観点から、植物抽出エキス、グリチルリチン酸二カリウム、チモール、メチルセルロース、イソ吉草酸イソアミル、ヘスペリジン、セバシン酸ジエチル、ハチミツ、グルタミン酸（Ｌ−グルタミン酸塩酸塩）が好ましく、中でも、ハッカ油、カンゾウエキス、アロエエキス、ユリエキス、ペパーミントエッセンス、グリチルリチン酸二カリウム、チモール、ハチミツ、セバシン酸ジエチル、メチルセルロース、グルタミン酸（Ｌ−グルタミン酸塩酸塩）がより好ましく、ハッカ油、カンゾウエキス、アロエエキス、ユリエキス、グリチルリチン酸二カリウム、チモール、メチルセルロース、グルタミン酸（Ｌ−グルタミン酸塩酸塩）がさらに好ましい。 Of these, plant extracts, dipotassium glycyrrhizinate, timol, methylcellulose, isoamyl isovalerate, hesperidin, diethyl sebacate, honey, and glutamate (L-glutamate) are preferable from the viewpoint of excellent periodontal tissue regeneration ability. Among them, peppermint oil, citrus extract, aloe extract, lily extract, peppermint essence, dipotassium glycyrrhizinate, timole, honey, diethyl sebacate, methyl cellulose, glutamate (L-glutamate) are more preferable, and peppermint oil, mint extract, Aloe extract, lily extract, dipotassium glycyrrhizinate, timol, methylcellulose and glutamic acid (L-glutamate) are more preferred.
植物抽出エキスは、植物からの粗抽出液を用いても、また、粗抽出液から分離精製したものを用いてもよい。その他の植物由来成分は、植物抽出エキスから分離、精製、単離したものを用いても、このようにして得られる物質と同等の物質を化学的に合成して用いてもよい。 As the plant extract, a crude extract from a plant may be used, or a crude extract separated and purified may be used. As the other plant-derived components, those separated, purified, and isolated from the plant extract may be used, or a substance equivalent to the substance thus obtained may be chemically synthesized and used.
植物抽出エキスを得る方法としては、特に限定されず、通常の抽出法が採用される。粗抽出液は、例えば植物の全体あるいはそれらの特定の部位を裁断機・スライサー・カッター・ピーラー等で細断したものを、水、熱水あるいは有機溶媒を単独あるいは組み合わせて得られる溶媒を用いて抽出することにより得ることができる。有機溶媒としては、メタノール、エタノール、１−プロパノール、２−プロパノール、１−ブタノール、２−ブタノール等のアルコール類、酢酸メチル、酢酸エチル等のエステル類、アセトン等のケトン類、ホルムアルデヒド、ジメチルスルホキシド等を挙げることができる。 The method for obtaining the plant extract is not particularly limited, and a usual extraction method is adopted. The crude extract is prepared by, for example, chopping the whole plant or a specific part thereof with a cutting machine, slicer, cutter, peeler, etc., and using a solvent obtained by using water, hot water, or an organic solvent alone or in combination. It can be obtained by extracting. Examples of the organic solvent include alcohols such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol and 2-butanol, esters such as methyl acetate and ethyl acetate, ketones such as acetone, formaldehyde, dimethyl sulfoxide and the like. Can be mentioned.
溶媒は、室温又は常温の溶媒を用いることもできるが、加熱溶媒や熱溶媒（溶媒を沸点付近に加熱したもの）を用いることもできる。 As the solvent, a solvent at room temperature or normal temperature can be used, but a heating solvent or a heat solvent (a solvent heated to near the boiling point) can also be used.
植物抽出エキスは、酸、アルカリの条件下で抽出する事もできる。酸としては、塩酸、硫酸、硝酸、リン酸等の無機酸、又は、酢酸、クエン酸、シュウ酸、コハク酸、ギ酸、プロピオン酸等の有機酸が挙げられる。アルカリとしては、アルカリ無機塩が好ましく用いられ、水酸化カリウム、水酸化ナトリウム等が挙げられる。 The plant extract can also be extracted under acid and alkaline conditions. Examples of the acid include inorganic acids such as hydrochloric acid, sulfuric acid, nitrate and phosphoric acid, and organic acids such as acetic acid, citric acid, oxalic acid, succinic acid, formic acid and propionic acid. As the alkali, an alkali-inorganic salt is preferably used, and examples thereof include potassium hydroxide and sodium hydroxide.
また、凍結乾燥粉末化法、高圧法や超高圧法を利用する事も可能である。 It is also possible to use the freeze-drying powder method, the high-pressure method, and the ultra-high pressure method.
粗抽出物の抽出条件の一例を以下に挙げる。抽出溶媒が有機溶媒の場合、溶媒の沸点以下であればよく抽出温度は特に制限はないが、好ましくは１℃〜１００℃、より好ましくは２０℃〜１００℃の範囲で、１時間〜２４時間、好ましくは１時間〜１０時間撹拌しながら行う。また、抽出溶媒が水の場合、抽出時の温度は特に限定されないが、加圧熱水による抽出方法を利用する場合もあるため、０℃〜２００℃が好ましく、２０℃〜１３０℃がより好ましい。また、反応時間も特に限定するものではないが、好ましくは数秒間〜数日間であり、更に好ましくは３０分〜２４時間である。なお、反応温度及び反応時間は、溶媒の種類と濃度により適宜選択することができる。 An example of the extraction conditions for the crude extract is given below. When the extraction solvent is an organic solvent, the extraction temperature is not particularly limited as long as it is equal to or lower than the boiling point of the solvent, but is preferably 1 ° C. to 100 ° C., more preferably 20 ° C. to 100 ° C. for 1 hour to 24 hours. , Preferably for 1 to 10 hours with stirring. When the extraction solvent is water, the temperature at the time of extraction is not particularly limited, but since an extraction method using pressurized hot water may be used, 0 ° C. to 200 ° C. is preferable, and 20 ° C. to 130 ° C. is more preferable. .. The reaction time is also not particularly limited, but is preferably several seconds to several days, and more preferably 30 minutes to 24 hours. The reaction temperature and reaction time can be appropriately selected depending on the type and concentration of the solvent.
得られた抽出物を遠心分離してその上清を、抽出液として得る。このように抽出されたものであれば、歯周組織再生能を有する成分を十分に含むことができる。かかる抽出液に水可溶性、酸性可溶性、アルカリ可溶性、あるいは有機溶媒可溶性の多糖画分が含まれる。 The obtained extract is centrifuged to obtain the supernatant as an extract. If it is extracted in this way, it can sufficiently contain a component having a periodontal tissue regeneration ability. Such extracts include water-soluble, acidic-soluble, alkali-soluble, or organic solvent-soluble polysaccharide fractions.
粗抽出物から植物抽出エキスを分離精製する方法としては、例えば、塩化セチルピリジニウム等の４級アンモニウム塩を添加し、藻類または植物の抽出物を沈殿させ、アルコール溶液で洗浄する方法やＤＥＡＥセルロース等の陰イオン交換樹脂等を用いたクロマトグラフィーを用いる方法もある。 Examples of the method for separating and purifying the plant extract from the crude extract include a method of adding a quaternary ammonium salt such as cetylpyridinium chloride to precipitate an algae or plant extract and washing with an alcohol solution, DEAE cellulose and the like. There is also a method of using chromatography using an anion exchange resin or the like.
このように抽出、精製した植物抽出エキスは、そのまま用いることもできる他、稀釈液で希釈したり、濃縮してエキスとして用いることもでき、さらには、凍結乾燥等により乾燥粉末物としたり、ペースト状に調製して用いることもできる。 The plant extract extracted and purified in this way can be used as it is, diluted with a dilute solution, concentrated and used as an extract, and further, it can be made into a dry powder by freeze-drying or the like, or a paste. It can also be prepared and used.
本発明では、このように抽出、精製した植物抽出エキスとして、そのままの状態で用いることもできるが、有機溶媒が含まれている場合には減圧蒸留等により有機溶媒を除去することが好ましい。また、本発明において、この抽出液は、液状のものを使用してもよいが、必要に応じて、減圧乾燥、凍結乾燥、噴霧乾燥等の乾燥処理を行って液体分を低減又は除去することにより、濃縮液状、半固形状、固形状、又は粉末状にしたものを使用してもよい。 In the present invention, the plant extract extracted and purified in this way can be used as it is, but when an organic solvent is contained, it is preferable to remove the organic solvent by vacuum distillation or the like. Further, in the present invention, a liquid extract may be used, but if necessary, a drying treatment such as vacuum drying, freeze drying, spray drying or the like is performed to reduce or remove the liquid content. Depending on the above, concentrated liquid, semi-solid, solid, or powdered products may be used.
本発明における植物抽出エキスとしては、市販品を用いることもできる。 As the plant extract in the present invention, a commercially available product can also be used.
（動物性成分）
本発明の歯周組織再生剤が含む動物性成分としては、例えば、真珠タンパク質エキス、コラーゲン、ラクトフェリン、ＤＨＡ（ドコサヘキサエン酸）等が挙げられる。ここで、本明細書において動物性成分とは、魚介類等の動物から抽出されるエキス、動物組織やミルク等の動物由来の物質から分離・精製される成分、又はこれらを原料として生成される成分のことをいう。
(Animal ingredient)
Examples of the animal component contained in the periodontium tissue regenerating agent of the present invention include pearl protein extract, collagen, lactoferrin, DHA (docosahexaenoic acid) and the like. Here, the animal component in the present specification is an extract extracted from an animal such as fish and shellfish, a component separated / purified from an animal-derived substance such as animal tissue or milk, or a component produced from these as a raw material. It refers to an ingredient.
これらのうち、歯周組織再生能に優れる観点から、真珠タンパク質エキスが好ましい。 Of these, the pearl protein extract is preferable from the viewpoint of excellent periodontal tissue regeneration ability.
真珠タンパク質エキスは、例えば、アコヤ貝の貝殻又は真珠を微細な粉末とし、これを化学的に処理（例えば、酸を加えてカルシウムを除去し、蛋白質を加水分解する等）して得られる蛋白分解物の水抽出液で、種々のアミノ酸とポリペプタイドを含有するものである。 The pearl protein extract is a protein decomposition obtained by, for example, making fine powder of Akoya shellfish or pearls and chemically treating the pearls (for example, adding an acid to remove calcium and hydrolyzing the protein). A water extract of a substance containing various amino acids and polypeptides.
（アルコール類）
本発明の歯周組織再生剤が含むアルコール類としては、例えば、糖アルコール、芳香族アルコール、多価アルコール等が挙げられ、歯周組織再生能に優れる観点から、これらのうち、Ｄ−マンニトール、濃グリセリン、ベンジルアルコールが好ましい。
(Alcohol)
Examples of alcohols contained in the periodontium regenerating agent of the present invention include sugar alcohols, aromatic alcohols, polyhydric alcohols, etc. From the viewpoint of excellent periodontal tissue regenerating ability, among these, D-mannitol and Concentrated glycerin and benzyl alcohol are preferable.
（ｐＨ調整剤）
本発明の歯周組織再生剤が含むｐＨ調整剤としては、例えば、各種有機酸又はその塩等として、クエン酸、グルコン酸、コハク酸、クエン酸ナトリウム、グルコン酸ナトリウム、コハク酸ナトリウム等が挙げられ、歯周組織再生能に優れる観点から、これらのうち、クエン酸、クエン酸ナトリウムが好ましく、クエン酸ナトリウムがより好ましい。
(PH regulator)
Examples of the pH adjuster contained in the periodontal tissue regenerating agent of the present invention include citric acid, gluconic acid, succinic acid, sodium citrate, sodium gluconate, sodium succinate and the like as various organic acids or salts thereof. Of these, citric acid and sodium citrate are preferable, and sodium citrate is more preferable, from the viewpoint of excellent periodontal tissue regeneration ability.
（その他の成分）
本発明の歯周組織再生剤が含む有効成分としてのその他の成分としては、歯周組織再生能に優れる観点から、例えば止血剤が挙げられ、このうちカルバゾクロム（和光純薬工業）が好ましい。
(Other ingredients)
Examples of other components as active ingredients contained in the periodontium regenerating agent of the present invention include hemostatic agents from the viewpoint of excellent periodontal tissue regenerating ability, of which carbazochrome (Wako Pure Chemical Industries, Ltd.) is preferable.
本発明の歯周組織再生剤中のこれらの有効成分の含有量は、概ね、０．０００００１質量％〜１２質量％であり、歯周組織再生能に優れる観点から、０．０００００１質量％〜５質量％であることが好ましく、０．００００１質量％〜３質量％であることがより好ましく、０．０００１質量％〜２質量％であることがさらに好ましく、０．０００５質量％〜１質量％であることが特に好ましく、０．００１質量％〜０．５質量％であることがより特に好ましい。なお、上述した各有効成分は、１種単独で用いてもよいし、２種以上を組み合わせて用いてもよい。 The content of these active ingredients in the periodontal tissue regeneration agent of the present invention is approximately 0.000001% by mass to 12% by mass, and from the viewpoint of excellent periodontal tissue regeneration ability, 0.000001% by mass to 5%. It is preferably by mass%, more preferably 0.00001% by mass to 3% by mass, further preferably 0.0001% by mass to 2% by mass, and 0.0005% by mass to 1% by mass. It is particularly preferable that the amount is 0.001% by mass to 0.5% by mass. Each of the above-mentioned active ingredients may be used alone or in combination of two or more.
本発明の歯周組織再生剤は、上記有効成分に加えて、他の任意成分として薬理学的又は生理学的に許容される一種又は二種以上の担体、賦形剤、結合剤、崩壊剤、滑沢剤、分散剤、界面活性化剤、可塑剤、懸濁剤、乳化剤、希釈剤、緩衝剤、抗酸化剤、細菌抑制剤等を含有していてもよい。さらに必要に応じて他の有効成分を含有していてもよい。 In addition to the above active ingredients, the periodontal tissue regenerating agent of the present invention includes one or more carriers, excipients, binders, disintegrants, which are pharmacologically or physiologically acceptable as other optional ingredients. It may contain a lubricant, a dispersant, a surfactant, a plasticizer, a suspending agent, an emulsifier, a diluent, a buffer, an antioxidant, a bacterial inhibitor and the like. Further, other active ingredients may be contained if necessary.
本発明の歯周組織再生剤は、医薬品、医薬部外品、食品等の分野において従来公知の任意の方法により製造することができる。その製造過程において、上記有効成分、その他の任意成分を公知のいかなる方法で添加・混合してもよい。 The periodontal tissue regenerating agent of the present invention can be produced by any conventionally known method in the fields of pharmaceuticals, quasi-drugs, foods and the like. In the manufacturing process, the above active ingredient and other optional ingredients may be added and mixed by any known method.
本発明の歯周組織再生剤は、歯周組織に対する再生及び／又は修復効果を有する。即ち、本発明の歯周組織再生剤は、歯周組織を構成する細胞を増殖、活性化させることができ、それにより歯周組織を再生及び／又は修復することができる。本発明の歯周組織再生剤は、歯周組織のうち、歯茎、歯根膜に対してより優れた効果を示し、特に歯根膜に対してさらに優れた効果を示す。そのため、本発明の歯周組織再生剤は、歯周病によって崩壊した歯周組織を効果的に再生及び／又は修復することができ、歯周病の治療のために好適に用いられる。特に、歯周病によって崩壊した歯根膜に対する再生及び／又は修復効果に優れるため、歯周病における歯根膜治療により好適に用いることができる。従って、本発明の歯周組織再生剤は、特に歯根膜再生剤、歯根膜修復剤、歯根膜・歯茎等の歯周組織を再生・修復するための歯周病の治療及び／又は改善剤としてより好適に用いることができる。さらに、本発明の歯周組織再生剤は、歯周病が進行し、歯根膜の崩壊が起こっている対象に対して、歯根膜再生剤、歯根膜修復剤、歯根膜・歯茎等の歯周組織を再生・修復するための歯周病の治療及び／又は改善剤として特に優れた効果を奏する。 The periodontal tissue regenerating agent of the present invention has a regenerating and / or repairing effect on the periodontal tissue. That is, the periodontal tissue regenerating agent of the present invention can proliferate and activate the cells constituting the periodontal tissue, thereby regenerating and / or repairing the periodontal tissue. The periodontal tissue regenerating agent of the present invention shows a more excellent effect on the gingiva and periodontal ligament among the periodontal tissues, and particularly shows a further excellent effect on the periodontal ligament. Therefore, the periodontal tissue regenerating agent of the present invention can effectively regenerate and / or repair the periodontal tissue disintegrated by periodontal disease, and is suitably used for the treatment of periodontal disease. In particular, since it has an excellent regeneration and / or restoration effect on the periodontal ligament collapsed due to periodontal disease, it can be suitably used for periodontal ligament treatment in periodontal disease. Therefore, the periodontal tissue regenerating agent of the present invention is particularly used as a periodontal disease regenerating agent, a periodontal ligament repairing agent, and a treatment and / or ameliorating agent for periodontal disease for regenerating and repairing periodontal tissues such as periodontal ligament and gum. It can be used more preferably. Further, the periodontal tissue regenerating agent of the present invention is used for periodontal diseases such as periodontal disease, periodontal ligament restoration agent, periodontal ligament, periodontal ligament, etc. It is particularly effective as a treatment and / or ameliorating agent for periodontal disease for regenerating and repairing tissues.
本発明の歯周組織再生剤の用途は特に限定されないが、例えば、上述のような歯周病治療薬、歯根膜治療薬等の医薬として、また、練歯磨等の歯磨類、洗口剤、マウスウォッシュ等の口腔用洗浄剤、歯茎に適用する美容液、トローチ、チューインガム等、歯周組織を構成する細胞の培養に用いることができる細胞培養用培地等に含有させて用いることができる。また、本発明の歯周組織再生剤の用法等も特に限定されず、例えば、１日数回（例えば、１〜４回程度、好ましくは２〜３回程度）、歯根膜や歯茎等の歯周組織に適量を塗布、塗擦、噴霧等して適用することで用いることができる。 The use of the periodontal tissue regenerating agent of the present invention is not particularly limited, but for example, as a medicine such as a periodontal disease therapeutic agent and a periodontal ligament therapeutic agent as described above, and as a toothpaste such as toothpaste and a mouthwash. It can be used by being contained in an oral cleaning agent such as mouthwash, a beauty liquid applied to the gums, a troche, a chewing gum, or a cell culture medium that can be used for culturing cells constituting the periodontal tissue. Further, the usage of the periodontal tissue regenerating agent of the present invention is not particularly limited, and for example, several times a day (for example, about 1 to 4 times, preferably about 2 to 3 times), periodontal diseases such as periodontal ligament and gums. It can be used by applying an appropriate amount to the tissue by applying, rubbing, spraying or the like.
［口腔用組成物］
本発明の歯周組織再生剤を含有する口腔用組成物も本発明の範囲である。本発明の口腔用組成物の形態としては、口中に適用できるものであれば特に制限されず、練り歯磨剤や粉歯磨剤等の歯磨組成物、洗口剤や液状歯磨剤等の液体口腔用組成物等として用いることができる。
[Oral composition]
Oral compositions containing the periodontal tissue regenerating agent of the present invention are also within the scope of the present invention. The form of the oral composition of the present invention is not particularly limited as long as it can be applied to the mouth, and is used for dentifrices such as dentifrices and powdered dentifrices, and for liquid oral cavity such as mouthwashes and liquid dentifrices. It can be used as a composition or the like.
口腔用組成物は、本発明の歯周組織再生剤以外に、本発明の効果を阻害しない範囲で、ポリエチレングリコール、１，３-ブチレングリコール、ジプロピレングリコール等のグリセリン以外の湿潤剤；サッカリンナトリウム、スクラロース等の甘味剤；メントール、アネトール等の香料；グリセリン脂肪酸エステル、ポリオキシエチレン硬化ヒマシ油等の非イオン性界面活性化剤；ラウリル硫酸ナトリウム等の陰イオン性界面活性化剤；上記有効成分以外のｐＨ調整剤、殺菌剤、抗炎症剤、防腐剤、着色剤、研磨剤、ビタミン剤、溶剤（エタノール等）等の、従来口腔用組成物において用いられる成分を含有することができる。 In addition to the periodontal tissue regenerating agent of the present invention, the oral composition is a wetting agent other than glycerin such as polyethylene glycol, 1,3-butylene glycol and dipropylene glycol; Sweeteners such as sclarose; Fragrances such as menthol and anetol; Nonionic surfactants such as glycerin fatty acid ester and polyoxyethylene hydrogenated castor oil; Anionic surfactants such as sodium lauryl sulfate; Other than the above active ingredients It can contain components conventionally used in oral compositions such as pH adjusters, bactericides, anti-inflammatory agents, preservatives, colorants, abrasives, vitamins, solvents (ethanol, etc.).
本発明の口腔用組成物が歯磨組成物である場合、保形性や使いやすさ、保存安定性の観点から粘結剤、増粘性シリカ等を含むことが好ましい。 When the oral composition of the present invention is a dentifrice composition, it preferably contains a binder, thickening silica and the like from the viewpoint of shape retention, ease of use and storage stability.
本発明の口腔用組成物における、植物由来成分、動物性成分等の歯周組織再生能を示す有効成分の最終的な含有量としては、成分毎に至適含有量は異なるものの、概ね、０．０００００１質量％〜１２質量％であり、０．０００００１質量％〜５質量％が好ましく、０．００００１質量％〜３質量％であることが好ましく、０．０００１質量％〜２質量％がより好ましく、０．０００５質量％〜１質量％がより好ましく、０．００１質量％〜０．５質量％が更に好ましい。上記有効成分の含有量が上記範囲内であると、本発明の口腔用組成物は歯周組織再生効果に優れると共に安全性にも優れるため、本発明の口腔用組成物を日常的に使用して、歯周組織を再生し、健康な口腔内環境を実現することが可能となる。 The final content of the active ingredient exhibiting the ability to regenerate periodontal tissue, such as a plant-derived ingredient and an animal ingredient, in the oral composition of the present invention is generally 0, although the optimum content differs for each ingredient. It is 0.000001% by mass to 12% by mass, preferably 0.000001% by mass to 5% by mass, preferably 0.00001% by mass to 3% by mass, and more preferably 0.0001% by mass to 2% by mass. , 0.0005% by mass to 1% by mass, more preferably 0.001% by mass to 0.5% by mass. When the content of the active ingredient is within the above range, the oral composition of the present invention is excellent in periodontium regeneration effect and also excellent in safety. Therefore, the oral composition of the present invention is used on a daily basis. Therefore, it is possible to regenerate the periodontium and realize a healthy oral environment.
本発明の口腔用組成物は、歯磨組成物、液体口腔用組成物等における従来公知の任意の方法により製造することができる。その製造過程において、上記有効成分、その他の成分を公知のいかなる方法で添加・混合してもよい。 The oral composition of the present invention can be produced by any conventionally known method for toothpaste compositions, liquid oral compositions and the like. In the manufacturing process, the above active ingredient and other ingredients may be added and mixed by any known method.
［歯周組織再生キット］
本発明は、本発明の歯周組織再生剤を含有する歯周組織再生キットも含む。歯周組織再生キットは、歯周病によって崩壊した歯周組織を効率的に再生・修復させるために、本発明の歯周組織再生剤を効果的に作用させるべく、複数の基材を予め組合せたものである。この基材としては特に限定されないが、例えば口腔洗浄剤、抗菌剤、薬剤塗布用基材等が挙げられる。また、歯ブラシ、マッサージ用の指サック等のデバイスと組み合わせることができる。
[Periodontal tissue regeneration kit]
The present invention also includes a periodontal tissue regeneration kit containing the periodontal tissue regeneration agent of the present invention. The periodontal tissue regeneration kit is a combination of a plurality of base materials in advance so that the periodontal tissue regeneration agent of the present invention can effectively act in order to efficiently regenerate and restore the periodontal tissue collapsed due to periodontal disease. It is a thing. The base material is not particularly limited, and examples thereof include an oral detergent, an antibacterial agent, and a base material for applying a drug. It can also be combined with devices such as toothbrushes and finger cots for massage.
［細胞培養用培地］
本発明は、本発明の歯周組織再生剤を含有する細胞培養用培地も含む。本発明の細胞培養用培地は、歯周組織を構成する細胞の増殖をより促進させることができる。そのため、歯根膜を構成する歯根膜線維芽細胞等をこの培地中で培養して細胞シートとし、歯周病で崩壊した歯根膜の代替として移植することも可能である。本発明の細胞培養用培地は、歯周組織再生剤に加えて、通常の細胞培養用の培地成分と同様の成分を含むことができる。
[Medium for cell culture]
The present invention also includes a cell culture medium containing the periodontal tissue regenerating agent of the present invention. The cell culture medium of the present invention can further promote the proliferation of cells constituting the periodontium. Therefore, periodontal ligament fibroblasts and the like constituting the periodontal ligament can be cultured in this medium to form a cell sheet, which can be transplanted as a substitute for the periodontal ligament that has collapsed due to periodontal disease. In addition to the periodontium tissue regenerating agent, the cell culture medium of the present invention can contain components similar to those of a normal cell culture medium.
［歯周組織再生方法］
本発明は、本発明の歯周組織再生剤を用いる歯周組織再生方法も含む。本発明の歯周組織再生方法は、本発明の歯周組織再生剤を用いることで、歯周病等により崩壊した歯根膜等の歯周組織を効率的に再生及び／又は修復することができる。
[Periodontal tissue regeneration method]
The present invention also includes a periodontal tissue regeneration method using the periodontal tissue regeneration agent of the present invention. The periodontal tissue regeneration method of the present invention can efficiently regenerate and / or repair periodontal tissue such as periodontal ligament that has collapsed due to periodontal disease or the like by using the periodontal tissue regeneration agent of the present invention. ..
［歯周組織増殖・活性化剤］
本発明の歯周組織増殖・活性化剤は、植物抽出エキス等の植物由来成分、真珠タンパク質エキス等の動物性成分、Ｄ−マンニトール、クエン酸ナトリウム、Ｌ−グルタミン酸塩酸塩、ベンジルアルコール、カルバゾクロム、濃グリセリン等のその他の成分のいずれかを有効成分として含む。本発明の歯周組織増殖・活性化剤は、これらのいずれかを有効成分として含むことで、歯根膜等の歯周組織を構成する細胞を増殖・活性化させ、歯周病等により損傷を受けた歯周組織を回復させることができる。本発明の歯周組織増殖・活性化剤が含む各成分については、本発明の歯周組織再生剤における説明を適用できる。
[Periodontal tissue growth / activator]
The periodontal tissue growth / activator of the present invention includes plant-derived components such as plant extract, animal components such as pearl protein extract, D-mannitol, sodium citrate, L-glutamate salt salt, benzyl alcohol, carbazochrome, and the like. Contains any of the other ingredients, such as concentrated glycerin, as the active ingredient. The periodontal tissue growth / activator of the present invention proliferates / activates cells constituting the periodontal tissue such as periodontal ligament by containing any of these as an active ingredient, and damages due to periodontal disease or the like. The received periodontal tissue can be restored. The description of the periodontal tissue regenerating agent of the present invention can be applied to each component contained in the periodontal tissue growth / activator of the present invention.
［歯周組織アンチエージング剤］
本発明の歯周組織アンチエージング剤は、植物抽出エキス等の植物由来成分、真珠タンパク質エキス等の動物性成分、Ｄ−マンニトール、クエン酸ナトリウム、Ｌ−グルタミン酸塩酸塩、ベンジルアルコール、カルバゾクロム、濃グリセリン等のその他の成分のいずれかを有効成分として含む。本発明の歯周組織アンチエージング剤は、これらのいずれかを有効成分として含むことで、歯根膜等の歯周組織を構成する細胞を増殖・活性化させ、老化等により衰えた歯周組織を復活させたり、年齢と共に気になる歯茎下がりを改善して、歯茎のハリやふっくら感を改善したり、それにより歯に食べ物が詰まり易くなる症状を改善したりして、老化を防止したりすることができる。本発明の歯周組織アンチエージング剤が含む各成分については、本発明の歯周組織再生剤における説明を適用できる。
[Periodontal tissue anti-aging agent]
The periodontal tissue anti-aging agent of the present invention includes plant-derived components such as plant extract, animal components such as pearl protein extract, D-mannitol, sodium citrate, L-glutamate salt salt, benzyl alcohol, carbazochrome, and concentrated glycerin. Any of the other ingredients such as, etc. is included as an active ingredient. The periodontal tissue anti-aging agent of the present invention contains any of these as an active ingredient to proliferate and activate the cells constituting the periodontal ligament such as the periodontal ligament, and to remove the periodontal tissue that has deteriorated due to aging or the like. Prevents aging by reviving, improving the periodontal ligament that is worrisome with age, improving the firmness and plumpness of the gums, and thereby improving the symptoms that make it easier for teeth to get clogged with food. be able to. The description of the periodontal tissue regenerating agent of the present invention can be applied to each component contained in the periodontal tissue anti-aging agent of the present invention.
以下に本発明を実施例に基づいて更に詳細に説明するが、本発明はこれら実施例に限定されるものではない。なお、各表中の数値の単位は、特に断りがない限り質量％である。 Hereinafter, the present invention will be described in more detail based on Examples, but the present invention is not limited to these Examples. The unit of the numerical value in each table is mass% unless otherwise specified.
［歯周組織再生剤の調製］
下記の表１に記載の処方に従い、常法にて、実施例１〜２３及び比較例１〜７の歯周組織再生剤を調製した。各歯周組織再生剤について下記試験を行い、評価した。
[Preparation of periodontal tissue regeneration agent]
The periodontal tissue regenerating agents of Examples 1 to 23 and Comparative Examples 1 to 7 were prepared by a conventional method according to the formulations shown in Table 1 below. The following tests were performed on each periodontal tissue regenerating agent and evaluated.
［評価］
（１）歯根膜線維芽細胞増殖評価
歯根膜線維芽細胞（Ｈｕｍａｎ Ｐｅｒｉｏｄｏｎｔａｌ Ｌｉｇａｍｅｎｔ Ｆｉｂｒｏｂｌａｓｔ：以下ＨＰＤＬＦと略す、ＳｃｉｅｎＣｅｌｌ Ｒｅｓｅａｒｃｈ Ｌａｂｏｒａｔｏｒｉｅｓ製）を１０％ＦＢＳ含有ＤＭＥＭ（Ｌｉｆｅ Ｔｅｃｈｎｏｌｏｇｉｅｓ製 Ｐｒｏｄｕｃｔ＃１１９９５−０６５）に懸濁し、９６ウェルプレート（Ｃｏｒｎｉｎｇ製 ＣｅｌｌＢＩＮＤ（登録商標） Ｐｒｏｄｕｃｔ＃３３００）に５×１０３ｃｅｌｌｓ／ウェルとなるように播種した。３７℃ ５％ＣＯ２で一晩培養し、翌日上清を除き、上記調製した歯周組織再生剤に交換した。３７℃ ５％ＣＯ２で４８〜７２時間培養後、上清を除き、ＦＢＳを含まないＤＭＥＭ（同上）で１度洗浄し、Ｃｅｌｌ Ｃｏｕｎｔｉｎｇ Ｋｉｔ−８（Ｄｏｊｉｎｄｏ製 Ｐｒｏｄｕｃｔ＃ＣＫ０４）試薬を１０％含有するＤＭＥＭ（同上）に交換した。３７℃で１時間〜３時間培養後、４５０ｎｍの吸光度を測定した。その結果を図１〜５に示す。
[Evaluation]
(1) periodontal ligament fibroblast growth evaluation periodontal ligament fibroblasts (H uman P erio d ontal L igament F ibroblast: hereinafter abbreviated as HPDLF, ScienCell Research Laboratories Ltd.) containing 10% FBS DMEM (Life Technologies Ltd. Product # 11995 It was suspended in −065) and seeded in a 96-well plate (CellBIND® Product # 3300 manufactured by Corning) at 5 × 10 3 cells / well. The cells were cultured overnight at 37 ° C. and 5% CO 2 , the supernatant was removed the next day, and the cells were replaced with the periodontal tissue regenerating agent prepared above. After culturing in 5% CO 2 at 37 ° C. for 48 to 72 hours, the supernatant is removed, washed once with DMEM (same as above) containing no FBS, and containing 10% of Cell Counting Kit-8 (Product # CK04 manufactured by Dojindo) reagent. It was replaced with DMEM (same as above). After culturing at 37 ° C. for 1 to 3 hours, the absorbance at 450 nm was measured. The results are shown in FIGS. 1 to 5.
図１より、イソ吉草酸イソアミル、ウイキョウ油、グリチルリチン酸二カリウム、Ｌ−グルタミン酸塩酸塩、セバシン酸ジエチル、チモール、濃グリセリン、ハチミツ、ハッカ油、ヘスペリジン、ペパーミントエッセンス、ベンジルアルコール、Ｄ−マンニトール、メチルセルロース、カルバゾクロムに、口腔の歯根膜線維芽細胞を増殖させる作用を持つことが判明した。
また、図２、図３、図４、図５より、アロエエキス、真珠タンパクエキス、ユリエキス、ハッカ油にも歯根膜線維芽細胞増殖作用があることが分かった。
歯周組織の修復・再生は、歯根膜細胞の増殖から始まり、細胞外マトリックスが形成されていくと考えられるため、上記の素材は歯根膜・歯周組織の修復・再生を促すと考えられる。
From FIG. 1, isoamyl isovalerate, uikyo oil, dipotassium glycyrrhizinate, L-glutamate salt salt, diethyl sebacate, timole, concentrated glycerin, honey, peppermint oil, hesperidin, peppermint essence, benzyl alcohol, D-mannitol, methylcellulose. , Carbazochrome was found to have the effect of proliferating oral periodontal ligament fibroblasts.
Further, from FIGS. 2, 3, 4, and 5, it was found that aloe extract, pearl protein extract, lily extract, and mentha oil also have a periodontal ligament fibroblast proliferation effect.
Since it is considered that the repair / regeneration of periodontal tissue begins with the proliferation of periodontal ligament cells and the extracellular matrix is formed, the above-mentioned material is considered to promote the repair / regeneration of periodontal ligament / periodontal tissue.
（２）歯根膜線維芽細胞浸潤効果の評価
歯根膜線維芽細胞（Ｈｕｍａｎ Ｐｅｒｉｏｄｏｎｔａｌ Ｌｉｇａｍｅｎｔ Ｆｉｂ
ｒｏｂｌａｓｔ：以下ＨＰＤＬＦと略す、ＳｃｉｅｎＣｅｌｌ Ｒｅｓｅａｒｃｈ Ｌａ
ｂｏｒａｔｏｒｉｅｓ製）を１０％ＦＢＳ含有ＤＭＥＭ（Ｌｉｆｅ Ｔｅｃｈｎｏｌｏｇ
ｉｅｓ製 Ｐｒｏｄｕｃｔ＃１１９９５−０６５）に懸濁したものを、３５ｍｍディッシュに０．９×１０６個となるように播種し、３７℃、５％ＣＯ２条件下で２４時間培養を行った。ピペットチップ（ＢＭ Ｂｉｏ ＢＭＴ−２００ＲＳ）を用いてディッシュ中央に創傷ライン（創傷部分）を作製し、次いで、同時にコントロール（０．２％ＦＢＳ含有ＤＭＥＭにＤＭＳＯを１％となるように加えたもの）又は０．２％ＦＢＳ含有ＤＭＥＭにユリエキスを１％加えたものに交換した。その直後及びそれから３時間ごとに、３７℃、５％ＣＯ２条件下で、タイムラプス（三洋電機株式会社製、ＭＵＬＴＩ ＣＥＬＬ−ＩＭＡＧＩＮＧ ＩＮＣＵＢＡＴＯＲ ＭＣＯＫ−５Ｍ）により、創傷ラインへの細胞の浸潤の撮影を行った。２１時間後に撮影した写真を、以下の図６に示す。また、２１時間後の創傷部分への細胞浸潤率（％）をコントロールと比較したグラフを図７に示す。
(2) Evaluation of periodontal ligament fibroblast infiltration effect Periodontal ligament fibroblast (Human Periodontal Ligament Fib)
roblast: Hereinafter abbreviated as HPDLF, SienCell Research La
DMEM (Life Technology) containing 10% FBS (manufactured by bovine serum)
those suspended in ies made Product # 11995-065), were seeded such that 0.9 × 10 6 cells in 35mm dishes, 37 ° C., were cultured for 24 hours under 5% CO 2. A wound line (wound portion) was created in the center of the dish using a pipette tip (BM Bio BMT-200RS), and then simultaneously controlled (DMEM containing 0.2% FBS plus 1% DMSO). Alternatively, it was replaced with DMEM containing 0.2% FBS plus 1% of lily extract. Immediately after that and every 3 hours thereafter, under the condition of 37 ° C. and 5% CO 2 , the infiltration of cells into the wound line was photographed by time lapse (MULTI CELL-IMAGING INCUBATOR MCOK-5M, manufactured by Sanyo Electric Co., Ltd.). It was. The photograph taken 21 hours later is shown in FIG. 6 below. In addition, a graph comparing the cell infiltration rate (%) to the wound portion after 21 hours with the control is shown in FIG.
図６及び７に示す通り、ユリエキスには創傷ラインへの細胞の浸潤を促進する効果が見られた。 As shown in FIGS. 6 and 7, the lily extract had an effect of promoting cell infiltration into the wound line.
歯根膜線維芽細胞（Ｌｏｎｚａ製）を１０％ＦＢＳ含有ＤＭＥＭ（Ｌｉｆｅ Ｔｅｃｈｎｏｌｏｇｉｅｓ製 Ｐｒｏｄｕｃｔ＃１１９９５−０６５）に懸濁したものを９６ウェルプレート（ｃｏｓｔａｒ３３００）に３．２×１０４個となるように播種し、３７℃、５％ＣＯ２条件下で２４時間培養を行った。ウェル中央に創傷ラインを作製し、次いでコントロール（ＤＭＳＯを０．１％となるよう０．２％ＦＢＳ含有ＤＭＥＭに添加したもの）またはハッカ油（ＤＭＳＯで１０％溶液となるよう溶解し、０．２％ＦＢＳ含有ＤＭＥＭに最終濃度が０．００４％となるよう添加したもの）に交換した。この時点で０時間の画像をＩｍａｇｅ Ｘｐｒｅｓｓ Ｍｉｃｒｏ ＸＬを用いて撮影し（Ｍｏｌｅｃｕｌａｒ Ｄｅｖｉｃｅｓ）、３７℃、５％ＣＯ２条件下で１８時間培養した後、更に撮影を行った。画像はＷｉｎＲＯＯＦを用いて解析を行った。 Periodontal ligament fibroblasts (manufactured by Lonza) suspended in DMEM (Product # 11995-055 manufactured by Life Technologies) containing 10% FBS were seeded on a 96-well plate (coster3300) so as to have 3.2 × 10 4 cells. Then, the cells were cultured at 37 ° C. under 5% CO 2 conditions for 24 hours. A wound line was made in the center of the well, followed by control (DMSO added to DMEM containing 0.2% FBS to 0.1%) or peppermint oil (dissolved in DMSO to a 10% solution, 0. It was replaced with DMEM containing 2% FBS (added so that the final concentration was 0.004%). At this point, a 0-hour image was taken using Image Xpress Micro XL (Molecular Devices), cultured at 37 ° C. under 5% CO 2 conditions for 18 hours, and then further photographed. Images were analyzed using WinROOF.
図８及び９に示す通り、ハッカ油には創傷ラインへの細胞の浸潤を促進する効果が見られた。 As shown in FIGS. 8 and 9, mint oil was found to have the effect of promoting cell infiltration into the wound line.
本発明の歯周組織再生剤、口腔用組成物、歯周組織増殖・活性化剤、及び歯周組織アンチエージング剤の製剤実施例を以下に示す。 Examples of the preparations of the periodontal tissue regenerating agent, the oral composition, the periodontal tissue growth / activator, and the periodontal tissue anti-aging agent of the present invention are shown below.
（製剤実施例１：口腔用軟膏剤）
Ａ
マクロゴール４００ 残量
マクロゴール４０００ ２５ｇ
ポリオキシエチレン硬化ヒマシ油６０ １ｇ
トコフェロール酢酸エステル ２ｇ
Ｂ
セチルピリジニウム塩化物水和物 ０．０５ｇ
アラントイン ０．３ｇ
グリチルリチン酸ジカリウム ０．４ｇ
カルバゾクロム ０．０２ｇ
Ｃ
ハッカ油 １ｇ
メントール １ｇ
ヒノキチオール ０．１ｇ
チモール ０．１ｇ
合計 １００ｇ
先ず、８０℃で上記Ａ成分を混合・溶解する。その溶解後、上記Ｂ成分を添加し、撹拌混合し十分に分散させ、冷却する。５０℃まで冷却してから上記Ｃ成分を添加し、撹拌混合して冷却することにより、本発明の口腔用軟膏剤を調製できる。
(Pharmaceutical Example 1: Oral ointment)
A
Macrogol 400 Remaining amount Macrogol 4000 25g
Polyoxyethylene hydrogenated
Tocopherol acetate 2g
B
Cetylpyridinium chloride hydrate 0.05g
Allantoin 0.3g
Dipotassium glycyrrhizinate 0.4g
Carbazochrome 0.02g
C
Mentha oil 1g
Menthol 1g
Hinokitiol 0.1g
Thymol 0.1g
100g in total
First, the component A is mixed and dissolved at 80 ° C. After its dissolution, the above component B is added, stirred and mixed, sufficiently dispersed, and cooled. The oral ointment of the present invention can be prepared by cooling to 50 ° C., adding the above-mentioned component C, stirring and mixing, and cooling.
（製剤実施例２：口腔用軟膏剤）
Ａ
ワセリン 残量
パラフィン １０ｇ
サラシミツロウ １０ｇ
セタノール １０ｇ
ポリオキシエチレン硬化ヒマシ油６０ １ｇ
トコフェロール酢酸エステル ２ｇ
Ｂ
濃グリセリン １ｇ
パンテノール ０．３ｇ
Ｃ
セチルピリジニウム塩化物水和物 ０．１ｇ
アラントイン ０．３ｇ
グリチルリチン酸ジカリウム ０．４ｇ
メチルセルロース ０．８ｇ
Ｄ
ハッカ油 １ｇ
ヒノキチオール ０．１ｇ
合計 １００ｇ
先ず、８０℃で上記Ａ成分を混合・溶解する。別途、上記Ｂ成分を混合しておく。溶解後のＡ成分に、Ｂ成分の混合物及び上記Ｃ成分を添加し、撹拌混合して十分に分散させ、冷却する。その後５０℃まで冷却してから上記Ｄ成分を添加し、撹拌混合し冷却することにより、本発明の口腔用軟膏剤を調製できる。
(Pharmaceutical Example 2: Oral ointment)
A
Vaseline remaining paraffin 10g
Sarashi beeswax 10g
Cetanol 10g
Polyoxyethylene hydrogenated
Tocopherol acetate 2g
B
Concentrated glycerin 1g
Panthenol 0.3g
C
Cetylpyridinium chloride hydrate 0.1g
Allantoin 0.3g
Dipotassium glycyrrhizinate 0.4g
Methyl cellulose 0.8g
D
Mentha oil 1g
Hinokitiol 0.1g
100g in total
First, the component A is mixed and dissolved at 80 ° C. Separately, the above B component is mixed. A mixture of the B component and the above C component are added to the A component after dissolution, and the mixture is stirred and mixed to sufficiently disperse and cool. After that, the oral ointment of the present invention can be prepared by cooling to 50 ° C., adding the above D component, stirring and mixing, and cooling.
（製剤実施例３：口腔用軟膏剤）
Ａ
流動パラフィン 残量
ポリエチレン末 ６ｇ
パルミチン酸デキストリン １ｇ
マイクロクリスタリンワックス ７ｇ
ポリオキシエチレン硬化ヒマシ油６０ １ｇ
Ｂ
セチルピリジニウム塩化物水和物 ０．０５ｇ
アラントイン ０．３ｇ
グリチルリチン酸ジカリウム ０．４ｇ
カルボキシビニルポリマー ２ｇ
ヒプロメロース １ｇ
軽質無水ケイ酸 ２ｇ
Ｃ
ウイキョウ油 １ｇ
ヒノキチオール ０．１ｇ
合計 １００ｇ
先ず、１００℃で上記Ａ成分を混合・溶解する。その溶解後に上記Ｂ成分を添加し、撹拌混合して十分に分散させ、冷却する。その後５０℃まで冷却してから上記Ｃ成分を添加し、撹拌混合して冷却することにより、本発明の口腔用軟膏剤を調製できる。
(Pharmaceutical Example 3: Oral ointment)
A
Liquid paraffin Remaining polyethylene powder 6g
Dextrin palmitate 1g
Microcrystalline wax 7g
Polyoxyethylene hydrogenated
B
Cetylpyridinium chloride hydrate 0.05g
Allantoin 0.3g
Dipotassium glycyrrhizinate 0.4g
Carboxyvinyl polymer 2g
Hypromellose 1g
Light anhydrous silicic acid 2g
C
Fennel oil 1g
Hinokitiol 0.1g
100g in total
First, the above component A is mixed and dissolved at 100 ° C. After the dissolution, the above component B is added, stirred and mixed to sufficiently disperse, and cooled. After that, the oral ointment of the present invention can be prepared by cooling to 50 ° C., adding the above-mentioned component C, stirring and mixing, and cooling.
（製剤実施例４：歯磨組成物）
Ａ
精製水 残量
グリチルリチン酸二カリウム ０．０５ｇ
Ｌ−グルタミン酸塩酸塩 ０．５ｇ
カルボキシメチルセルロース １ｇ
濃グリセリン ５ｇ
香料 ０．２５ｇ
ソルビトール液 ３０ｇ
Ｂ
イソプロピルメチルフェノール ０．１ｇ
酢酸トコフェロール ０．１ｇ
プロピレングリコール １０ｇ
ハッカ油 ０．５ｇ
Ｃ
シリカ ８ｇ
ラウレス硫酸酸ナトリウム ２ｇ
合計 １００ｇ
先ず、上記Ａ成分を撹拌・溶解後、６０℃で加熱溶解した上記Ｂ成分を投入する。その後、上記Ｃ成分を投入し撹拌することにより、本発明の歯磨組成物を調製できる。
(Pharmaceutical Example 4: Toothpaste composition)
A
Purified water remaining amount Dipotassium glycyrrhizinate 0.05 g
L-Glutamic acid salt 0.5g
Carboxymethyl cellulose 1g
Concentrated glycerin 5g
Fragrance 0.25g
Sorbitol solution 30g
B
Isopropylmethylphenol 0.1g
Tocopherol acetate 0.1g
Propylene glycol 10g
Mentha oil 0.5g
C
Silica 8g
Sodium Laureth Sulfate 2g
100g in total
First, the component A is stirred and dissolved, and then the component B heated and dissolved at 60 ° C. is added. Then, the toothpaste composition of the present invention can be prepared by adding the above-mentioned component C and stirring the mixture.
（製剤実施例５：洗口剤（洗口液））
Ａ
精製水 残量
グリチルリチン酸二カリウム ０．０５ｇ
酢酸トコフェロール ０．０５ｇ
濃グリセリン １０ｇ
クエン酸 ０．１ｇ
クエン酸ナトリウム ０．２５ｇ
フェノキシエタノール ０．３ｇ
香料 ０．１ｇ
ハチミツ ０．０１ｇ
Ｂ
イソプロピルメチルフェノール ０．０５ｇ
ポリオキシエチレン硬化ヒマシ油６０ ２．５ｇ
チモール ０．０１ｇ
ｌ−メントール ０．５ｇ
合計 １００ｇ
上記Ａ成分を溶解後、６０℃で加熱溶解した上記Ｂ成分を上記Ａ成分に添加し撹拌することにより、本発明の洗口剤を調製できる。
(Formulation Example 5: Mouthwash (mouthwash))
A
Purified water remaining amount Dipotassium glycyrrhizinate 0.05 g
Tocopherol acetate 0.05g
Concentrated glycerin 10g
Citric acid 0.1g
Sodium citrate 0.25g
Phenoxyethanol 0.3g
Fragrance 0.1g
Honey 0.01g
B
Isopropylmethylphenol 0.05g
Polyoxyethylene hydrogenated
Thymol 0.01g
l-menthol 0.5g
100g in total
The mouthwash of the present invention can be prepared by adding the component B, which has been dissolved by heating at 60 ° C. to the component A, and stirring the mixture.
（製剤実施例６：洗口剤(洗口液)）
Ａ
精製水 残量
塩化セチルピリジニウム ０．０５ｇ
ε−アミノカプロン酸 ０．０５ｇ
ポリエチレングリコール １０ｇ
Ｄ−マンニトール ０．５ｇ
クエン酸 ０．１ｇ
クエン酸ナトリウム ０．２５ｇ
メチルパラベン ０．２ｇ
香料 ０．１ｇ
ペパーミントエッセンス ０．０５ｇ
アロエエキス ０．１ｇ
カンゾウエキス ０．０１ｇ
合計 １００ｇ
上記各成分の全量を撹拌溶解することにより、本発明の洗口剤を調製できる。
(Pharmaceutical Example 6: Mouthwash (mouthwash))
A
Purified water remaining amount Cetylpyridinium chloride 0.05g
ε-aminocaproic acid 0.05g
Polyethylene glycol 10g
D-mannitol 0.5g
Citric acid 0.1g
Sodium citrate 0.25g
Methylparaben 0.2g
Fragrance 0.1g
Peppermint Essence 0.05g
Aloe extract 0.1g
Licorice extract 0.01g
100g in total
The mouthwash of the present invention can be prepared by stirring and dissolving the entire amount of each of the above components.
（製剤実施例７：歯茎マッサージジェル）
Ａ
精製水 残量
グリチルリチン酸二カリウム ０．０３ｇ
ソルビトール １０ｇ
濃グリセリン １０ｇ
エタノール ５ｇ
クエン酸 ０．０５ｇ
クエン酸ナトリウム ０．２ｇ
香料 ０．４ｇ
真珠タンパク質エキス ０．０５ｇ
ユリエキス ０．０５ｇ
加水分解コラーゲン ０．０１ｇ
Ｂ
ポリオキシエチレン硬化ヒマシ油６０ ２ｇ
イソプロピルメチルフェノール ０．００５ｇ
酢酸トコフェロール ０．０１ｇ
ハッカ油 ０．１ｇ
ｌ−メントール ０．２ｇ
Ｃ
ポリエチレングリコール４００ １０ｇ
キサンタンガム １ｇ
ヒアルロン酸ナトリウム ０．０５ｇ
合計 １００ｇ
上記Ａ成分を溶解後、５０℃で加熱溶解した上記Ｂ成分を添加して撹拌溶解させる。その後、上記Ｃ成分を撹拌分散したものを添加して撹拌することにより、本発明の歯茎マッサージジェルを調製できる。
(Pharmaceutical Example 7: Gingival massage gel)
A
Purified water remaining amount Dipotassium glycyrrhizinate 0.03 g
Sorbitol 10g
Concentrated glycerin 10g
Ethanol 5g
Citric acid 0.05g
Sodium citrate 0.2g
Fragrance 0.4g
Pearl protein extract 0.05g
Yuri extract 0.05g
Hydrolyzed collagen 0.01g
B
Polyoxyethylene hydrogenated castor oil 602 g
Isopropylmethylphenol 0.005g
Tocopherol acetate 0.01g
Mentha oil 0.1g
l-menthol 0.2g
C
Polyethylene glycol 400 10g
Xanthan gum 1g
Sodium hyaluronate 0.05g
100g in total
After the component A is dissolved, the component B that has been heated and dissolved at 50 ° C. is added and dissolved by stirring. Then, the gum massage gel of the present invention can be prepared by adding and stirring the above-mentioned C component.
Claims (1)
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| JP6257549B2 (en) * | 2015-03-25 | 2018-01-10 | サンスター株式会社 | Aqueous oral composition |
| JP7105057B2 (en) | 2016-12-05 | 2022-07-22 | ロート製薬株式会社 | oral composition |
| JP7466884B2 (en) * | 2017-08-30 | 2024-04-15 | 丸善製薬株式会社 | Type I collagen production promoter in normal human gingival fibroblasts |
| JP6449398B2 (en) * | 2017-09-14 | 2019-01-09 | サンスター株式会社 | Aqueous oral composition |
| JP2020094029A (en) * | 2018-06-25 | 2020-06-18 | ロート製薬株式会社 | Oral composition |
| JP2020019713A (en) * | 2018-07-30 | 2020-02-06 | ライオン株式会社 | Gum cell proliferation promoter |
| JP2022526636A (en) * | 2019-04-16 | 2022-05-25 | ザ プロクター アンド ギャンブル カンパニー | A kit containing an electromagnetic radiation source and a semi-solid polyphase oral composition comprising hydrophilic bleach particles. |
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| JP2023017035A (en) | 2023-02-02 |
| JP2016153396A (en) | 2016-08-25 |
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