JP7002799B1 - Preventive or therapeutic agent for Alzheimer's disease - Google Patents
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Abstract
【課題】新規なジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤の提供。【解決手段】白金コロイドとパラジウムコロイドとを含有する、ジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤。【選択図】なしPROBLEM TO BE SOLVED: To provide a prophylactic or therapeutic agent for a disease caused by a novel Porphyromonas gingivalis and / or Streptococcus mutans. SOLUTION: A preventive or therapeutic agent for a disease caused by Gingivalis bacterium and / or mutans bacterium, which contains a platinum colloid and a palladium colloid. [Selection diagram] None
Description
本発明は、ジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤に関する。本発明は、より詳細には、アルツハイマー型認知症の予防又は治療剤に関する。 The present invention relates to a prophylactic or therapeutic agent for diseases caused by Porphyromonas gingivalis and / or Streptococcus mutans. The present invention, in more detail, relates to a prophylactic or therapeutic agent for Alzheimer's disease.
ポルフィロモナス・ジンバリス（Ｐｏｒｐｈｙｒｏｍｏｎａｓ ｇｉｎｇｉｖａｌｉｓ。以下、「ジンジバリス菌」ともいう。）は、ヒトの口腔内に存在する細菌である。ジンジバリス菌は、重要な歯周病源細菌として知られているが、歯周病以外の疾患との関連も注目されている。例えば、非特許文献１では、ジンジバリス菌は、アルツハイマー病の脳における病原体の最有力候補の一つであり、アルツハイマー病を引き起こす一連の事象に関与している可能性が指摘されている。また、ジンジバリス菌等の歯周細菌が心血管疾患発症の要因である可能性があること（非特許文献２）、及びジンジバリス菌による内皮細胞への侵入及び寄生がアテローム性動脈硬化症という炎症反応を悪化させる可能性があること（非特許文献３）も指摘されており、さらに、脳膿瘍からジンジバリス菌が検出され、口腔領域からの感染が強く疑われた事例（非特許文献４）も報告されている。 Porphyromonas gingivalis (hereinafter, also referred to as "Gingivalis bacterium") is a bacterium present in the human oral cavity. Porphyromonas gingivalis is known as an important source of periodontal disease, but its association with diseases other than periodontal disease has also attracted attention. For example, Non-Patent Document 1 points out that Porphyromonas gingivalis is one of the leading candidates for pathogens in the brain of Alzheimer's disease and may be involved in a series of events that cause Alzheimer's disease. In addition, periodontal bacteria such as Porphyromonas gingivalis may be a factor in the onset of cardiovascular disease (Non-Patent Document 2), and invasion and infestation of endothelial cells by Porphyromonas gingivalis is an inflammatory reaction called atherosclerosis. It has also been pointed out that there is a possibility of worsening the disease (Non-Patent Document 3), and a case in which Gingivalis bacteria were detected in a brain abscess and infection from the oral region was strongly suspected (Non-Patent Document 4) was also reported. Has been done.
また、ストレプトコッカス・ミュータンス（Ｓｔｒｅｐｔｏｃｏｃｃｕｓ ｍｕｔａｎｓ。以下、「ミュータンス菌」ともいう。）も、人の口腔内に存在する細菌であり、虫歯（う歯）の代表的な原因菌として知られている。 In addition, Streptococcus mutans (hereinafter, also referred to as "mutans bacterium") is a bacterium existing in the human oral cavity and is known as a typical causative bacterium of dental caries (dental caries). ..
ジンジバリス菌及びミュータンス菌と様々な疾患との関連が指摘される中で、ジンジバリス菌及び／又はミュータンス菌に作用して、上記のような疾患を予防又は治療することのできる予防又は治療剤への需要が高まっている。これに対し、例えば、特許文献１には、粒度分布における最頻値が１．０μｍ以下である乳酸菌を有効成分として含有することを特徴とする口腔用組成物が、う蝕関連細菌のミュータンス菌や歯周病関連細菌のジンジバリス菌類に対して、選択的に作用を示し、それゆえ口腔内フローラを良い環境に導くことが記載されている。 While the association between Porphyromonas gingivalis and mutans and various diseases has been pointed out, a preventive or therapeutic agent capable of acting on porphyromonas gingivalis and / or mutans to prevent or treat the above-mentioned diseases. Demand for is increasing. On the other hand, for example, in Patent Document 1, the oral composition characterized by containing lactic acid bacteria having a most frequent value of 1.0 μm or less in the particle size distribution as an active ingredient is a mutans of caries-related bacteria. It has been described that it acts selectively on bacteria and periodontal disease-related bacteria, Streptococcus chinensis, and therefore leads to a favorable environment for the oral flora.
本発明は、新規なジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤の提供を目的とする。 An object of the present invention is to provide a prophylactic or therapeutic agent for a disease caused by a novel Porphyromonas gingivalis and / or Streptococcus mutans.
本発明者らは、白金コロイドとパラジウムコロイドとを共に用いることでジンジバリス菌及び／又はミュータンス菌の増殖を抑制できることを見出し、本発明を完成するに至った。 The present inventors have found that the growth of gingivalis and / or mutans can be suppressed by using both platinum colloid and palladium colloid, and have completed the present invention.
すなわち、本発明は、以下の各発明に関する。
［１］白金コロイドとパラジウムコロイドとを含有する、ジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤。
［２］疾患がアルツハイマー型認知症、歯周病、心血管疾患、アテローム性動脈硬化症、脳膿瘍、及び虫歯からなる群より選択される１種以上である、［１］に記載の予防又は治療剤。
［３］疾患がアルツハイマー型認知症である、［２］に記載の予防又は治療剤。
［４］疾患が歯周病である、［２］に記載の予防又は治療剤。
［５］疾患が脳膿瘍である、［２］に記載の予防又は治療剤。
［６］疾患が虫歯である、［２］に記載の予防又は治療剤。
［７］白金コロイドの濃度が０．０８～１６ｍＭの液剤である、［１］～［６］のいずれかに記載の予防又は治療剤。
［８］パラジウムコロイドに対する白金コロイドのモル比が、１／３０～１０／１である、［１］～［７］のいずれかに記載の予防又は治療剤。
［９］パラジウムコロイドの濃度が０．１～３０ｍＭの液剤である、［１］～［８］のいずれかに記載の予防又は治療剤。
That is, the present invention relates to each of the following inventions.
[1] A prophylactic or therapeutic agent for diseases caused by gingivalis and / or mutans, which contains platinum colloid and palladium colloid.
[2] The prevention or prevention according to [1], wherein the disease is one or more selected from the group consisting of Alzheimer-type dementia, periodontal disease, cardiovascular disease, atherosclerosis, brain abscess, and tooth decay. Therapeutic agent.
[3] The prophylactic or therapeutic agent according to [2], wherein the disease is Alzheimer's disease.
[4] The prophylactic or therapeutic agent according to [2], wherein the disease is periodontal disease.
[5] The prophylactic or therapeutic agent according to [2], wherein the disease is a brain abscess.
[6] The prophylactic or therapeutic agent according to [2], wherein the disease is dental caries.
[7] The prophylactic or therapeutic agent according to any one of [1] to [6], which is a liquid preparation having a platinum colloid concentration of 0.08 to 16 mM.
[8] The prophylactic or therapeutic agent according to any one of [1] to [7], wherein the molar ratio of platinum colloid to palladium colloid is 1/30 to 10/1.
[9] The prophylactic or therapeutic agent according to any one of [1] to [8], which is a liquid preparation having a palladium colloid concentration of 0.1 to 30 mM.
本発明によれば、新規なジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤の提供が可能となる。 According to the present invention, it is possible to provide a novel prophylactic or therapeutic agent for diseases caused by Porphyromonas gingivalis and / or Streptococcus mutans.
以下、本発明の好適な実施形態について詳細に説明する。ただし、本発明は以下の実施形態に限定されるものではない。 Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the following embodiments.
本実施形態に係るジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤は、白金コロイドとパラジウムコロイドとを含有する。当該予防又は治療剤は、白金コロイドとパラジウムコロイドとを含有する液剤であってよい。 The preventive or therapeutic agent for diseases caused by Zingivalis and / or mutans according to the present embodiment contains platinum colloid and palladium colloid. The preventive or therapeutic agent may be a liquid agent containing platinum colloid and palladium colloid.
白金コロイドは、水にコロイド状に分散する白金粒子である。白金コロイドは、公知の方法（例えば、特公昭５７－４３１２５号公報、特公昭５９－１２０２４９号公報、特公平２－４３８０１号公報、特開平９－２２５３１７号公報、特開平１０－１７６２０７号公報等に記載の方法）により製造することができる。白金コロイドの製造方法としては、薬理学的又は生理学的に許容されるものであれば、特に制限されないが、例えば、沈殿法又は金属塩還元反応法として知られる化学的な方法、あるいは燃焼法として知られる物理的な方法等を利用することができる。白金コロイドの製造方法としては、ジンジバリス菌及び／又はミュータンス菌の増殖抑制作用をより有効に奏するという観点から、燃焼法を用いることが好ましい。 Platinum colloids are platinum particles that are colloidally dispersed in water. Platinum colloids can be prepared by known methods (for example, Japanese Patent Application Laid-Open No. 57-43125, Japanese Patent Application Laid-Open No. 59-120249, Japanese Patent Application Laid-Open No. 2-435801, Japanese Patent Application Laid-Open No. 9-225317, Japanese Patent Application Laid-Open No. 10-176207, etc. It can be manufactured by the method described in 1). The method for producing the platinum colloid is not particularly limited as long as it is pharmacologically or physiologically acceptable, and is, for example, as a chemical method known as a precipitation method or a metal salt reduction reaction method, or a combustion method. Known physical methods and the like can be used. As a method for producing a platinum colloid, it is preferable to use a combustion method from the viewpoint of more effectively suppressing the growth of gingivalis and / or mutans.
燃焼法としては、例えば、塩化白金酸溶液及び低級アルコールの混合溶液、並びに、水素ガスを、それぞれ別の供給系から送出し、燃焼させた水素ガス炎と、上記混合溶液とを混合させ８３０～８７０℃で燃焼させ、燃焼火炎をコロイド生成槽中の槽底近くに達する渦流を生じさせた液体分散媒中に吹き込むこと等によって、白金コロイドを製造する方法が挙げられる。 As a combustion method, for example, a mixed solution of a platinum chloride solution and a lower alcohol, and hydrogen gas are sent from different supply systems, and the burned hydrogen gas flame is mixed with the above mixed solution to 830 to. Examples thereof include a method of producing a platinum colloid by burning at 870 ° C. and blowing a combustion flame into a liquid dispersion medium that has generated a vortex that reaches near the bottom of the colloid generation tank.
予防又は治療剤が液剤である場合において、白金コロイドの濃度は特に限定されず、使用される白金コロイドの種類、予防又は治療剤の用途、製剤形態、使用方法等によって適宜設定される。液剤における白金コロイドの濃度は、ジンジバリス菌及び／又はミュータンス菌の増殖抑制作用をより有効に奏するという観点から、液剤全量に対して、０．０８～１６ｍＭであることが好ましく、０．１～１０ｍＭであることが好ましく、０．４～８ｍＭであることがさらに好ましい。 When the prophylactic or therapeutic agent is a liquid agent, the concentration of the platinum colloid is not particularly limited, and is appropriately set depending on the type of platinum colloid used, the use of the prophylactic or therapeutic agent, the pharmaceutical form, the method of use, and the like. The concentration of platinum colloid in the liquid preparation is preferably 0.08 to 16 mM with respect to the total amount of the liquid preparation, preferably 0.1 to 16 mM, from the viewpoint of more effectively suppressing the growth of gingivalis and / or mutans bacteria. It is preferably 10 mM, more preferably 0.4 to 8 mM.
パラジウムコロイドは、水にコロイド状に分散するパラジウム粒子である。パラジウムコロイドは、公知の方法（例えば、特公昭５７－４３１２５号公報、特公昭５９－１２０２４９号公報、特公平２－４３８０１号公報、特開平９－２２５３１７号公報、特開平１０－１７６２０７号公報等に記載の方法）により製造することができる。パラジウムコロイドの製造方法としては、薬理学的又は生理学的に許容されるものであれば、特に制限されないが、例えば、沈殿法又は金属塩還元反応法として知られる化学的な方法、あるいは燃焼法として知られる物理的な方法等を利用することができる。パラジウムコロイドの製造方法として、白金の酸化による劣化を防止するという観点から、燃焼法を用いることが好ましい。 Palladium colloids are palladium particles that are colloidally dispersed in water. Palladium colloids can be prepared by known methods (for example, Japanese Patent Application Laid-Open No. 57-43125, Japanese Patent Application Laid-Open No. 59-120249, Japanese Patent Application Laid-Open No. 2-435801, Japanese Patent Application Laid-Open No. 9-225317, Japanese Patent Application Laid-Open No. 10-176207, etc. It can be manufactured by the method described in 1). The method for producing the palladium colloid is not particularly limited as long as it is pharmacologically or physiologically acceptable, and is, for example, as a chemical method known as a precipitation method or a metal salt reduction reaction method, or a combustion method. Known physical methods and the like can be used. As a method for producing a palladium colloid, it is preferable to use a combustion method from the viewpoint of preventing deterioration due to oxidation of platinum.
燃焼法としては、例えば、塩化パラジウム溶液及び低級アルコールの混合溶液、並びに、水素ガスを、それぞれ別の供給系から送出し、燃焼させた水素ガス炎と、上記混合溶液とを混合させ６３０～６７０℃で燃焼させ、燃焼火炎をコロイド生成槽中の槽底近くに達する渦流を生じさせた液体分散媒中に吹き込むこと等によって、パラジウムコロイドを製造する方法が挙げられる。 As a combustion method, for example, a mixed solution of a palladium chloride solution and a lower alcohol, and hydrogen gas are sent from different supply systems and burned, and the hydrogen gas flame and the above mixed solution are mixed and 630 to 670. Examples thereof include a method of producing a palladium colloid by burning at ° C. and blowing a combustion flame into a liquid dispersion medium that has generated a vortex that reaches near the bottom of the colloid-forming tank.
予防又は治療剤が液剤である場合において、パラジウムコロイドの濃度は特に限定されず、使用されるパラジウムコロイドの種類、併用される白金コロイドの種類及び濃度、予防又は治療剤の用途、製剤形態、使用方法等によって適宜設定される。液剤におけるパラジウムコロイドの濃度は、白金の酸化による劣化を防止し、かつ継続投与した場合にも副作用を起こりにくくするという観点から、液剤全量に対して、０．１～３０ｍＭであることが好ましく、０．４～１６ｍＭであることがより好ましく、０．８～１２ｍＭであることがさらに好ましい。 When the prophylactic or therapeutic agent is a liquid, the concentration of the palladium colloid is not particularly limited, and the type and concentration of the palladium colloid used, the type and concentration of the platinum colloid used in combination, the use of the prophylactic or therapeutic agent, the formulation form, and the use. It is set appropriately depending on the method and the like. The concentration of palladium colloid in the liquid preparation is preferably 0.1 to 30 mM with respect to the total amount of the liquid preparation from the viewpoint of preventing deterioration due to oxidation of platinum and preventing side effects even when continuously administered. It is more preferably 0.4 to 16 mM, and even more preferably 0.8 to 12 mM.
パラジウムコロイドに対する白金コロイドのモル比（パラジウムに対する白金のモル比（Ｐｔ／Ｐｄ））は、特に制限されず、使用される白金コロイド及びパラジウムコロイドの種類及び濃度、該ＮＫ細胞活性化剤の用途、製剤形態、使用方法等に応じて適宜設定される。パラジウムコロイドに対する白金コロイドのモル比は、ジンジバリス菌及び／又はミュータンス菌の増殖抑制作用をより有効に奏するという観点から、好ましくは１／３０～１０／１であり、より好ましくは１／９～３／１である。 The molar ratio of platinum colloid to palladium colloid (molar ratio of platinum to palladium (Pt / Pd)) is not particularly limited, and the type and concentration of platinum colloid and palladium colloid used, the use of the NK cell activator, and the use of the NK cell activator. It is appropriately set according to the formulation form, usage method, and the like. The molar ratio of platinum colloid to palladium colloid is preferably 1/30 to 10/1, more preferably 1/9 to 1, from the viewpoint of more effectively suppressing the growth of gingivalis and / or mutans. It is 3/1.
本実施形態に係るジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤は、界面活性剤をさらに含有していてもよい。界面活性剤としては、薬理学的又は生理学的に許容されるものであれば特に制限されず、非イオン性界面活性剤、両性界面活性剤、陰イオン性界面活性剤、陽イオン性界面活性剤のいずれであってもよい。本実施形態に係るジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤は、ジンジバリス菌及び／又はミュータンス菌の増殖抑制作用をより有効に奏するという観点から、界面活性剤として、非イオン性界面活性剤を含有することが好ましい。 The prophylactic or therapeutic agent for diseases caused by Gingivalis and / or mutans according to the present embodiment may further contain a surfactant. The surfactant is not particularly limited as long as it is pharmacologically or physiologically acceptable, and is a nonionic surfactant, an amphoteric surfactant, an anionic surfactant, or a cationic surfactant. It may be any of. The preventive or therapeutic agent for diseases caused by gingivalis and / or mutans according to the present embodiment can be used as a surfactant as a surfactant from the viewpoint of more effectively suppressing the growth of gingivalis and / or mutans. It preferably contains a nonionic surfactant.
非イオン性界面活性剤としては、例えば、モノラウリン酸ＰＯＥ（２０）ソルビタン（ポリソルベート２０）、モノパルミチン酸ＰＯＥ（２０）ソルビタン（ポリソルベート４０）、モノステアリン酸ＰＯＥ（２０）ソルビタン（ポリソルベート６０）、トリステアリン酸ＰＯＥ（２０）ソルビタン（ポリソルベート６５）、モノオレイン酸ＰＯＥ（２０）ソルビタン（ポリソルベート８０）等のＰＥＯソルビタン脂肪酸エステル；ＰＯＥ（４０）硬化ヒマシ油（ポリオキシエチレン硬化ヒマシ油４０）、ＰＯＥ（６０）硬化ヒマシ油（ポリオキシエチレン硬化ヒマシ油６０）等のＰＯＥ硬化ヒマシ油；ＰＯＥ（９）ラウリルエーテル等のＰＯＥアルキルエーテル；ＰＯＥ（２０）ＰＯＰ（４）セチルエーテル等のＰＯＥ－ＰＯＰアルキルエーテル；ＰＯＥ（１９６）ＰＯＰ（６７）グリコール（ポロクサマー４０７、プルロニック（登録商標）Ｆ１２７）、ＰＯＥ（２００）ＰＯＰ（７０）グリコール等のポリオキシエチレン・ポリオキシプロピレンブロックコポリマー；ポリオキシエチレンヒマシ油３５、ポリオキシエチレンヒマシ油４０、ポリオキシエチレンヒマシ油５０、ポリオキシエチレンヒマシ油６０等の酸化エチレンの平均付加モル数が３０を上回るポリオキシエチレンヒマシ油等が挙げられる。本実施形態に係るジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤において、上記非イオン性界面活性剤を、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。
Examples of the nonionic surfactant include monolauric acid POE (20) sorbitan (polysorbate 20), monopalmitic acid POE (20) sorbitan (polysorbate 40), monostearate POE (20) sorbitan (polysorbate 60), and birds. PEO sorbitan fatty acid esters such as POE stearate (20) sorbitan (polysorbate 65), POE monooleic acid (20) sorbitan (polysorbate 80); POE (40) hardened castor oil (polyoxyethylene hydrogenated castor oil 40), POE ( 60) POE hardened castor oil such as cured castor oil (polyoxyethylene hydrogenated castor oil 60); POE alkyl ether such as POE (9) lauryl ether; POE-POP alkyl ether such as POE (20) POP (4) cetyl ether Polyoxyethylene / polyoxypropylene block copolymers such as POE (196) POP (67) glycol (Poroxummer 407, Pluronic® F127), POE (200) POP (70) glycol; Polyoxyethylene castor oil 35, Examples thereof include polyoxyethylene glycol oils such as polyoxyethylene glycol oil 40,
本実施形態に係るジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤は、固体（例えば、粉末）、液体、ペースト等のいずれの形状であってもよく、タブレット（素錠、糖衣錠、発泡錠、フィルムコート錠、チュアブル錠、トローチ剤等を含む。）、カプセル剤、丸剤、粉末剤（散剤）、細粒剤、顆粒剤、液剤（懸濁液、乳濁液、シロップ等を含む。）、ペースト等の形態であってもよい。これらの各種製剤は、薬理学的又は生理学的に許容されるものであれば、賦形剤、滑沢剤、結合剤、崩壊剤、安定剤、懸濁化剤等の添加剤を混合し、周知の方法で製造することができる。 The prophylactic or therapeutic agent for diseases caused by gingivalis and / or mutans according to the present embodiment may be in any form such as solid (for example, powder), liquid, paste, etc., and is a tablet (uncoated tablet, etc.). Includes sugar-coated tablets, effervescent tablets, film-coated tablets, chewable tablets, troches, etc.), capsules, rounds, powders (powder), fine granules, granules, liquids (suspensions, emulsions, syrups) Etc.), may be in the form of a paste or the like. These various preparations are mixed with additives such as excipients, lubricants, binders, disintegrants, stabilizers and suspending agents as long as they are pharmacologically or physiologically acceptable. It can be manufactured by a well-known method.
本実施形態に係るジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤は、医薬品、医薬部外品、食品組成物及び飼料組成物等の製品として、又はこれら製品の成分として使用することができる。当該食品組成物は、例えば、健康食品、機能性表示食品、特別用途食品、栄養補助食品、サプリメント及び特定保健用食品であってもよい。食品組成物の具体例としては、例えば、飲料等が挙げられる。上記製品は、ジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療用であってよい。ジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療用製品における白金コロイド及びパラジウムコロイドそれぞれの濃度は、上記例示したとおりであってよい。 The prophylactic or therapeutic agent for diseases caused by gingivalis and / or mutans according to the present embodiment is used as a product such as a pharmaceutical product, a quasi drug, a food composition and a feed composition, or as a component of these products. can do. The food composition may be, for example, a health food, a food with a functional claim, a food for special use, a dietary supplement, a supplement, and a food for specified health use. Specific examples of the food composition include beverages and the like. The product may be for the prevention or treatment of diseases caused by Gingivalis and / or mutans. The concentrations of the platinum colloid and the palladium colloid in the preventive or therapeutic products for diseases caused by Zingivalis and / or mutans may be as exemplified above.
本実施形態に係るジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤によれば、ジンジバリス菌及び／又はミュータンス菌の増殖を抑制することにより、ジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療が可能となる。ジンジバリス菌及び／又はミュータンス菌に起因する疾患としては、例えば、歯周病、アルツハイマー病（アルツハイマー型認知症）、心血管疾患、アテローム性動脈硬化症、脳膿瘍、虫歯（う歯）等が挙げられる。本実施形態に係る予防又は治療剤は、歯周病、アルツハイマー病（アルツハイマー型認知症）、心血管疾患、アテローム性動脈硬化症、脳膿瘍、及び虫歯（う歯）からなる群より選択される１種以上の予防剤又は治療剤であってよい。 According to the prophylactic or therapeutic agent for diseases caused by gingivalis and / or mutans according to the present embodiment, gingivalis and / or mutans by suppressing the growth of gingivalis and / or mutans. It is possible to prevent or treat diseases caused by. Diseases caused by Gingivalis and / or mutans include, for example, periodontal disease, Alzheimer's disease (Alzheimer's disease), cardiovascular disease, atherosclerosis, cerebral abscess, dental caries (dental caries) and the like. Can be mentioned. The prophylactic or therapeutic agent according to the present embodiment is selected from the group consisting of periodontal disease, Alzheimer's disease (Alzheimer-type dementia), cardiovascular disease, atherosclerosis, brain abscess, and dental caries (dental caries). It may be one or more prophylactic or therapeutic agents.
心血管疾患とは、心臓と血管に関する疾患である。心血管疾患としては、例えば、狭心症、心筋梗塞等の冠状動脈性心疾患；脳梗塞、脳出血等の脳血管疾患；末梢動脈疾患；リウマチ性心疾患；深部静脈血栓症；肺塞栓症等が挙げられる。アテローム性動脈硬化症は、動脈硬化症の最も一般的な形態であり、動脈硬化性心疾患、冠状動脈性心疾患、末梢血管疾患、脳血管疾患等を引き起こす原因となる。 Cardiovascular disease is a disease related to the heart and blood vessels. Examples of cardiovascular diseases include coronary heart disease such as angina and myocardial infarction; cerebrovascular disease such as cerebral infarction and cerebral hemorrhage; peripheral arterial disease; rheumatic heart disease; deep venous thrombosis; pulmonary embolism and the like. Can be mentioned. Atherosclerosis is the most common form of arteriosclerosis and causes arteriosclerotic heart disease, coronary arterial heart disease, peripheral vascular disease, cerebrovascular disease and the like.
本実施形態に係るジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤は、ヒトに投与又は摂取されても、非ヒト哺乳動物に投与又は摂取されてもよい。本実施形態に係るジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤の投与量（摂取量）は、白金コロイドの質量に換算して、成人１日あたり、例えば、０．０６～６ｍｇであることが好ましく、０．１～４ｍｇであることがより好ましく、０．３～３ｍｇであることがさらに好ましい。投与量は、個体の状態、年齢等に応じて適宜決定することができる。 The prophylactic or therapeutic agent for diseases caused by Zingivalis and / or mutans according to the present embodiment may be administered or ingested to humans or may be administered or ingested to non-human mammals. The dose (intake) of the prophylactic or therapeutic agent for diseases caused by Gingivalis and / or mutans according to the present embodiment is converted into the mass of platinum colloid, for example, 0.06 per adult day. It is preferably to 6 mg, more preferably 0.1 to 4 mg, and even more preferably 0.3 to 3 mg. The dose can be appropriately determined according to the condition, age, etc. of the individual.
本実施形態に係るジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤は、経口投与（摂取）されてもよく、非経口投与されてもよいが、経口投与されることが好ましい。ジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤は、１日あたりの白金コロイドの質量に換算した値が上記範囲内にあれば、１日１回投与されてもよく、１日複数回に分けて投与されてもよい。 The prophylactic or therapeutic agent for diseases caused by gingivalis and / or mutans according to the present embodiment may be orally administered (ingested) or parenterally, but is preferably orally administered. .. The prophylactic or therapeutic agent for diseases caused by gingivalis and / or mutans may be administered once a day as long as the value converted to the mass of platinum colloid per day is within the above range. It may be administered in multiple divided doses daily.
本実施形態に係るジンジバリス菌及び／又はミュータンス菌に起因する疾患の予防又は治療剤は、１週間以上継続して投与されてよく、２週間以上継続して投与（摂取）されてよく、３週間以上継続して投与（摂取）されてよく、４週間以上継続して投与（摂取）されてよい。 The prophylactic or therapeutic agent for diseases caused by Gingivalis and / or mutans according to the present embodiment may be continuously administered for 1 week or longer, and may be continuously administered (ingested) for 2 weeks or longer. 3 It may be continuously administered (ingested) for a week or longer, and may be continuously administered (ingested) for 4 weeks or longer.
以下に、実施例を挙げて本発明をさらに詳細に説明する。 Hereinafter, the present invention will be described in more detail with reference to examples.
検体として、株式会社東洋厚生製薬所製の白金パラジウムコロイド溶液（ＰＡＰＬＡＬ（登録商標）水）を準備した。当該白金パラジウムコロイド溶液は、６ｍｌの水溶液（液剤）中、白金コロイドを１．２ｍｇ、パラジウムコロイドを１．８ｍｇ含む。 As a sample, a platinum-palladium colloidal solution (PAPLAL® water) manufactured by Toyo Kosei Pharmaceutical Co., Ltd. was prepared. The platinum-palladium colloid solution contains 1.2 mg of platinum colloid and 1.8 mg of palladium colloid in a 6 ml aqueous solution (solution).
〔ジンジバリス菌及びミュータンス菌に対する増殖抑制効果の検証〕
（コロニー形成阻害試験）
まず、ジンジバリス菌及びミュータンス菌を継代培養した。培養は、ジンジバリス菌には変法ＧＡＭ寒天培地を、ミュータンス菌にはＭＳ寒天培地をそれぞれ用いて、３７℃のインキュベーター内にて前者は嫌気的、後者は好気的環境下で行った。
[Verification of growth inhibitory effect on gingivalis and mutans bacteria]
(Colonization inhibition test)
First, gingivalis and mutans were subcultured. The culture was carried out in an anaerobic environment in the incubator at 37 ° C. in an anaerobic environment and in an aerobic environment, using a modified GAM agar medium for gingivalis bacteria and an MS agar medium for mutans bacteria.
培養したジンジバリス菌を変法ＧＡＭ寒天培地上に、ミュータンス菌をＭＳ寒天培地上に、それぞれコンラージ棒を用いて均一に塗布した。それぞれの表面に、上記の検体を染み込ませたディスクと、後述する３種の対照ディスクを設置し、３７℃のインキュベーター内にて、ジンジバリス菌は嫌気的環境下、ミュータンス菌は好気的環境下で２４時間培養した。３種の対照ディスクとしては、対照１：リン酸緩衝液を染み込ませたディスク、対照２：パラジウムコロイド溶液（パラジウムコロイド濃度０．３ｇ／Ｌの水溶液）を染み込ませたディスク、及び、対照３：白金コロイド溶液（白金コロイド濃度０．２ｇ／Ｌの水溶液）を染み込ませたディスクを用いた。培養後のサンプルを撮影した画像を図１（ジンジバリス菌）及び図２（ミュータンス菌）に示す。 The cultured Gingivalis bacterium was uniformly applied onto the modified GAM agar medium, and the mutans bacterium was uniformly applied onto the MS agar medium using a spreader. A disc impregnated with the above sample and three types of control discs, which will be described later, were placed on each surface, and in an incubator at 37 ° C, gingivalis bacteria were in an anaerobic environment and mutans bacteria were in an aerobic environment. Incubated under 24 hours. The three control discs include control 1: a disc impregnated with a phosphate buffer, control 2: a disc impregnated with a palladium colloid solution (an aqueous solution having a palladium colloid concentration of 0.3 g / L), and control 3: A disk impregnated with a platinum colloid solution (an aqueous solution having a platinum colloid concentration of 0.2 g / L) was used. Images of the sample after culturing are shown in FIGS. 1 (Gingivalis bacterium) and FIG. 2 (Mutans bacterium).
図１、図２の各画像中に見られる４つのディスクは、上から時計回りに、対照１、対照２、対照３、及び検体を染み込ませたディスクである。図１、図２のとおり、ジンジバリス菌とミュータンス菌のどちらについても、対照１のディスクの周囲では、ディスクから離れた場所と同様にコロニーが形成されていたのに対して、検体、対照２、及び対照３のディスクの周囲では、ディスクから離れた場所と比較してコロニーが少ない傾向にあり、検体、対照２、及び対照３に、ジンジバリス菌及びミュータンス菌に対する増殖抑制効果があることが確認された。 The four discs seen in each of the images of FIGS. 1 and 2 are discs impregnated with control 1, control 2, control 3, and a sample clockwise from the top. As shown in FIGS. 1 and 2, for both Porphyromonas gingivalis and Streptococcus mutans, colonies were formed around the disc of control 1 as in the place away from the disc, whereas the specimen and control 2 were formed. , And around the disc of control 3, there is a tendency for fewer colonies compared to a place away from the disc, and the specimen, control 2, and control 3 have a growth inhibitory effect on gingivalis and mutans. confirmed.
（ＳＥＭ観察）
上記の検体を５０％又は１００％添加した培養液を用意し、上記のコロニー形成阻害試験と同様にして培養したジンジバリス菌を当該培養液に播種して、３７℃のインキュベーター内にて嫌気的環境下で２４時間培養した。また、対照として、検体と蒸留水のどちらも添加しない培養液、及び、検体に変えて蒸留水を５０％又は１００％添加した培養液を用いて、同様にジンジバリス菌の培養を行った。培養後の菌の形態像を走査型電子顕微鏡（ＳＥＭ）にて観察した。検体と蒸留水のどちらも添加しない培養液、５０％蒸留水添加培養液、５０％ＰＡＰＬＡＬ（登録商標）水添加培養液、１００％蒸留水添加培養液、及び１００％ＰＡＰＬＡＬ（登録商標）水添加培養液を用いた場合のＳＥＭ像を、それぞれ図３～図７に順に示す。
(SEM observation)
A culture solution containing 50% or 100% of the above sample was prepared, and the gingivalis bacterium cultured in the same manner as in the above colony formation inhibition test was inoculated into the culture solution, and the anaerobic environment was placed in an incubator at 37 ° C. Incubated under 24 hours. Further, as a control, the gingivalis bacterium was similarly cultured using a culture solution to which neither the sample nor distilled water was added, and a culture solution to which 50% or 100% of distilled water was added instead of the sample. The morphological image of the bacterium after culturing was observed with a scanning electron microscope (SEM). A culture solution to which neither a sample nor distilled water is added, a culture solution to which 50% distilled water is added, a culture solution to which 50% PAPLAL (registered trademark) water is added, a culture solution to which 100% distilled water is added, and 100% PAPLAL (registered trademark) water addition. The SEM images when the culture solution is used are shown in order in FIGS. 3 to 7, respectively.
図５、図７のとおり、検体を添加した培養液では、破壊されている菌体が数多く見られた。特に、検体を１００％添加した培養液では、溶菌も数多く見られた。 As shown in FIGS. 5 and 7, many cells were destroyed in the culture medium to which the sample was added. In particular, in the culture solution to which 100% of the sample was added, many lysates were also observed.
（検体中の生菌数の変化）
まず、ジンジバリス菌を５％馬脱繊維血液加Ｂｒｕｃｅｌｌａ Ａｇａｒ（ＢＤ ＢＢＬ（登録商標））で３５℃±１℃、４～７日間嫌気培養した後、生理食塩水に浮遊させ、菌数が１０８～１０９／ｍＬとなるように調製して、試験菌液を作製した。
(Changes in the number of viable bacteria in the sample)
First, gingivalis bacteria were anaerobically cultured in Brucella Agar (BD BBL (registered trademark)) with 5% horse defibered blood at 35 ° C ± 1 ° C for 4 to 7 days, and then suspended in physiological saline to increase the number of bacteria to 108 . A test bacterial solution was prepared by adjusting the content to ~ 109 / mL.
上記の検体１０ｍｌに試験菌液０．１ｍｌを接種して試験液を作製し、室温で１分、３分、及び５分保存後の試験液中の生菌数を測定した。生菌数の測定は、５％馬脱繊維血液加Ｂｒｕｃｅｌｌａ Ａｇａｒ（ＢＤ ＢＢＬ（登録商標））を用いた平板塗抹培養法（３５℃±１℃、５～７日間嫌気培養）により行った。なお、生菌数の測定にあたり、検体の影響を受けずに生菌数の測定ができるように、試験液をＳＤＣＬＰ培地（日本製薬株式会社製）で１０倍に希釈した。また、対照として、検体に変えて生理食塩水を用いて同様の試験を行った。結果を表１に示す。 A test solution was prepared by inoculating 10 ml of the above sample with 0.1 ml of the test bacterial solution, and the viable cell count in the test solution after storage at room temperature for 1 minute, 3 minutes, and 5 minutes was measured. The viable cell count was measured by a plate smear culture method (35 ° C ± 1 ° C, anaerobic culture for 5 to 7 days) using Brucella Agar (BD BBL (registered trademark)) with 5% horse defibered blood. In measuring the viable cell count, the test solution was diluted 10-fold with SDCLP medium (manufactured by Nihon Pharmaceutical Co., Ltd.) so that the viable cell count could be measured without being affected by the sample. In addition, as a control, a similar test was conducted using physiological saline instead of the sample. The results are shown in Table 1.
Claims (8)
前記疾患がアルツハイマー型認知症、歯周病、脳膿瘍、及び虫歯からなる群より選択される１種以上である、予防又は治療剤。 A prophylactic or therapeutic agent for diseases caused by gingivalis and / or mutans, which contains platinum colloid and palladium colloid.
A prophylactic or therapeutic agent, wherein the disease is one or more selected from the group consisting of Alzheimer-type dementia, periodontal disease, brain abscess, and dental caries .
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2004073723A1 (en) | 2003-02-20 | 2004-09-02 | She Tec Co., Ltd. | Medical drug containing fine particle of noble metal |
| JP2005139157A (en) | 2003-11-07 | 2005-06-02 | Shetech:Kk | Medicine for preventing and/or treating cerebral infarction |
| CN102335110A (en) | 2010-07-19 | 2012-02-01 | 金基暎 | Powder toothpaste combination comprising Au particles and manufacturing method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2004073723A1 (en) | 2003-02-20 | 2004-09-02 | She Tec Co., Ltd. | Medical drug containing fine particle of noble metal |
| JP2005139157A (en) | 2003-11-07 | 2005-06-02 | Shetech:Kk | Medicine for preventing and/or treating cerebral infarction |
| CN102335110A (en) | 2010-07-19 | 2012-02-01 | 金基暎 | Powder toothpaste combination comprising Au particles and manufacturing method thereof |
| JP2014034538A (en) | 2012-08-08 | 2014-02-24 | Ibio Epoch:Kk | Tooth paste and its production method, and dental rinse |
Non-Patent Citations (4)
| Title |
|---|
| Toyama Medical Journal，2015年，Vol.26, No.1，p.45-49 |
| 実験医学，2019年，Vol.37, No.2(増刊)，p.110-117 |
| 小児口腔外科，2020年，Vol.30, No.1，p.32-36 |
| 日本歯周病学会会誌，2017年，Vol.59(suppl-1)，p.123 |
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