JP2017222601A - Neurodegenerative disease therapeutic agent - Google Patents
Neurodegenerative disease therapeutic agent Download PDFInfo
- Publication number
- JP2017222601A JP2017222601A JP2016119085A JP2016119085A JP2017222601A JP 2017222601 A JP2017222601 A JP 2017222601A JP 2016119085 A JP2016119085 A JP 2016119085A JP 2016119085 A JP2016119085 A JP 2016119085A JP 2017222601 A JP2017222601 A JP 2017222601A
- Authority
- JP
- Japan
- Prior art keywords
- lactic acid
- strain
- acid bacteria
- lactobacillus
- fermented
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
Description
本発明は神経変性疾患の予防又は治療剤に関する。 The present invention relates to a preventive or therapeutic agent for neurodegenerative diseases.
神経変性疾患は、系統的な神経細胞の変性、脱落に基づく神経回路網の破綻により引き起こされる病態である。代表的な疾患として、アルツハイマー型認知症（アルツハイマー病）、パーキンソン病、筋萎縮性側索硬化症、緑内障が知られているほか、自閉症との関連性も議論されている。
このうち、アルツハイマー型認知症は初老期に発病する進行性の神経変性疾患であり、認知症の５０％を占めるとされ、近年、その患者数は高齢者人口の増加とともに増え、わが国の６５歳の高齢者の１４％ほどが現在認知症を患っており、社会的に重要な疾患となっている。
A neurodegenerative disease is a pathological condition caused by the breakdown of a neural network based on systematic degeneration and loss of nerve cells. As typical diseases, Alzheimer-type dementia (Alzheimer's disease), Parkinson's disease, amyotrophic lateral sclerosis, glaucoma are known, and the relationship with autism is also discussed.
Among them, Alzheimer's dementia is a progressive neurodegenerative disease that develops in early age and is said to account for 50% of dementia. In recent years, the number of patients has increased with the increase in the elderly population, and 65 years old in Japan. About 14% of elderly people currently have dementia, which is a socially important disease.
神経変性疾患の原因である神経変性死のメカニズムには多くの分子群が複雑に関与し、それらの発現、機能異常が生じているものと予想される。しかしながら、その分子病態については解明されたものはほとんどなく、有効な神経変性の抑制方法も確立されていない。アルツハイマー病の発症機序として現在最も有力な説は、ベータアミロイドタンパク質が脳内に異常沈着することにより神経変性が誘導され、その結果認知障害を発症するというものである。 Many molecular groups are involved in the mechanism of neurodegenerative death, which is a cause of neurodegenerative diseases, and their expression and dysfunction are expected to occur. However, little has been elucidated about the molecular pathology, and no effective method for suppressing neurodegeneration has been established. The most promising theory for the pathogenesis of Alzheimer's disease is that neurodegeneration is induced by abnormal deposition of beta-amyloid protein in the brain, resulting in cognitive impairment.
アルツハイマー病治療薬の代表的なものとして現在コリンエステラーゼ阻害を主作用に持つドネペジル等が上市されているが、当該薬剤は記憶学習機能に関連するコリン作動性神経を賦活することにより一過的に症状を緩和するいわば対処療法的な位置づけにあり、神経の変性の進行抑制ないしは神経再生を誘導する機序やアルツハイマー病発症原因自体を取り除く原因療法的治療薬は未だ存在していないのが現状である。 Donepezil, which has cholinesterase inhibition as its main action, is currently on the market as a representative drug for Alzheimer's disease, but the drug temporarily causes symptoms by activating cholinergic nerves related to memory learning function. In other words, it is positioned as a coping therapy, and there are currently no causative therapies to suppress the progression of nerve degeneration or to induce nerve regeneration and to eliminate the cause of Alzheimer's disease .
したがって、中枢神経系の神経細胞に作用し、神経細胞を活性化し、神経突起の萎縮を抑制或いは神経突起の形成を促進させて神経変性を抑制し、それに伴う病態や臨床症状を予防もしくは治療することができる神経変性疾患剤の開発が切望されている。 Therefore, it acts on neurons in the central nervous system, activates neurons, suppresses neurite atrophy or promotes neurite formation, suppresses neurodegeneration, and prevents or treats pathological conditions and clinical symptoms associated therewith Development of a neurodegenerative disease agent that can be performed is eagerly desired.
例えば、特許文献１では、アルツハイマー病、パーキンソン病等の神経変性疾患の治療、予防のために、海馬BDNF発現を増加させる目的で、ビフィドバクテリウム・ロンガムATCC BAA-９９９を含む食用組成物、健康補助食品、医療用組成物が提案されている。
また、特許文献２では、乳酸菌の表面にワクチン抗原たるＡβ（アミロイドβ）分子種を発現する乳酸菌を固体に投与することにより抗アミロイドβ抗体を誘導し、アミロイドβに対する免疫を固体に誘導してアルツハイマー病の予防、治療方法が提案されている。
また、特許文献３では、抗アルツハイマー用組成物及び食品として、大豆を納豆菌等で発酵させた発酵物の抽出物を含む組成物が提案されている。
また、特許文献４では、酸化及び抗老化機能及び認知症改善効果を有する新規の乳酸菌として、キムチから分離したラクトバチルス・ペントーサス変種プランタルム（Lactobacillus pentosus var. plantarum）Ｃ２９ ＫＣＣＭ１１２９１Ｐ及びラクトバチルス・カルバタス（Lactobacillus curvatus）Ｃ３ ＫＣＣＭ４３０００９を有効成分として含む抗酸化及び抗老化薬学組成物及び健康機能食品、認知症予防または治療用組成物及び認知症予防または改善用健康機能食品、Ｃ２９またはＣ３菌株で発酵した発酵組成物を有効成分として含む認知症の予防または治療用組成物が提案されている。
また、非特許文献１では、柑橘類の成分ノビレチンや生薬エキスにNGF（nerve growth factor）神経突起伸展作用を増強する効果のあることが報告されている。
For example, Patent Document 1 discloses an edible composition containing Bifidobacterium longum ATCC BAA-999 for the purpose of increasing hippocampal BDNF expression for the treatment and prevention of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Health supplements and medical compositions have been proposed.
Further, in Patent Document 2, anti-amyloid β antibody is induced by administering lactic acid bacteria expressing Aβ (amyloid β) molecular species, which are vaccine antigens, on the surface of lactic acid bacteria, and immunity against amyloid β is induced solidly. Methods for preventing and treating Alzheimer's disease have been proposed.
Moreover, in patent document 3, the composition containing the extract of the fermented material which fermented soybean with natto bacteria etc. as an anti-Alzheimer composition and food is proposed.
In Patent Document 4, as a novel lactic acid bacterium having an oxidative and anti-aging function and a dementia improving effect, Lactobacillus pentosus var. Plantarum C29 KCCM11291P and Lactobacillus carbatus (Lactobacillus) isolated from kimchi curvatus) Antioxidant and anti-aging pharmaceutical composition containing C3 KCCM430009 as an active ingredient, health functional food, composition for preventing or treating dementia, health functional food for preventing or improving dementia, fermented composition fermented with C29 or C3 strain A composition for preventing or treating dementia has been proposed which comprises a product as an active ingredient.
Further, Non-Patent Document 1 reports that citrus component nobiletin and herbal extracts have an effect of enhancing NGF (nerve growth factor) neurite extension action.
一方、八朔（学名：Citrus hassaku Hort．）は、元々は広島が原産のミカン科の常緑高木で、柑橘類の一つである。また、その果皮は、芳香性の健胃薬として腹痛、膨満感、便秘等の治療又は予防に使用され、また咳又は痰を鎮めるためにも使用される。さらに、八朔中に含まれるノビレチンにはアンドロゲン受容体結合阻害作用があり、男性型禿頭、多毛症、脂漏症等に有効であることが報告されている（特許文献５）。
また、田七人参、杜仲、甘草及び黄精を含む生薬組成物（例えば、「養生片仔廣」（登録商標）」）は、血中ＧＰＴ（ＡＬＴとも呼ぶ）及びＧＯＴ（ＡＳＴ）を正常化し、肝機能改善作用を有するサプリメントとして知られ、肝癌に対する抑制作用を有すること（特許文献６）や、コレステロール血症、高血圧症等の生活習慣病の改善に（特許文献７）に有効であることも報告されている。
On the other hand, Yawata (scientific name: Citrus hassaku Hort.) Was originally an evergreen Takagi of the citrus family native to Hiroshima and is one of the citrus fruits. Further, the pericarp is used as an aromatic stomachic medicine for the treatment or prevention of abdominal pain, bloating, constipation, etc., and also used to calm cough or sputum. Furthermore, nobiletin contained in Yawata has an androgen receptor binding inhibitory action and has been reported to be effective for male type baldness, hirsutism, seborrhea (Patent Document 5).
In addition, a herbal composition containing ginseng, ginseng, licorice and yellow spirit (for example, “cured piece pupa” (registered trademark)) normalizes blood GPT (also called ALT) and GOT (AST), It is also known as a supplement having a function-improving action and has an inhibitory action on liver cancer (Patent Document 6) and is also effective for improving lifestyle-related diseases such as cholesterolemia and hypertension (Patent Document 7). Has been.
しかしながら、八朔や田七人参、杜仲、甘草及び黄精を含む生薬組成物を含む培地で乳酸菌培養して得られた発酵物が、神経変性疾患に有効であることは、これまで全く知られていない。 However, it has never been known that a fermented product obtained by culturing lactic acid bacteria in a medium containing a herbal composition including yam, ginseng, carrot, licorice and yellow spirit is effective for neurodegenerative diseases. .
本発明は、神経突起の形成を促進し、アルツハイマー病、パーキンソン病、緑内障等の神経変性疾患の予防又は治療に有効な手段を提供することを目的とする。 An object of the present invention is to provide neurite formation and provide an effective means for preventing or treating neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and glaucoma.
本発明者らは、上記課題に鑑み、鋭意研究を重ねた結果、酒粕を含む八朔果汁を培地とした植物乳酸菌発酵物又は田七人参、杜仲、甘草及び黄精を含む生薬組成物の植物乳酸菌発酵物に、神経突起形成促進作用があり、これらが神経変性疾患の予防又は治療に有用であることを見出した。 In light of the above-mentioned problems, the present inventors have conducted extensive research, and as a result, fermented plant lactic acid bacteria using yam juice containing sake lees, or plant lactic acid bacteria fermentation of herbal medicine composition containing ginseng, ginseng, licorice and yellow spirit. It has been found that these products have a neurite formation promoting action and are useful for the prevention or treatment of neurodegenerative diseases.
すなわち、本発明は、以下の１）〜４）に係るものである。
１）八朔の植物乳酸菌発酵物、又は田七人参、杜仲、甘草及び黄精から選ばれる１種以上を含有する生薬組成物の植物乳酸菌発酵物を有効成分とする神経変性疾患の予防又は治療剤。
２）植物乳酸菌が、ラクトバチルス プランタラム、ラクトバチルス ブレビス、ペディオコッカス ペントサセウス、及びラクトバチルス ロイテリから選ばれる１種以上である１）に記載の神経変性疾患の予防、改善又は治療剤。
３）植物乳酸菌が、ラクトバチルス プランタラムＳＮ１３Ｔ株、ラクトバチルス プランタラムＳＮ３５Ｎ株、ぺディオコッカス ペントサセウスＬＰ２８株及びラクトバチルス ブレビス１７４Ａ株及びラクトバチルス ロイテリＢＭ５３−１株から選ばれる１種以上である１）に記載の神経変性疾患の予防、改善又は治療剤。
４）生薬組成物が、田七人参、杜仲、甘草及び黄精の全てを含む１）〜３）のいずれかの神経変性疾患の予防又は治療剤。
That is, the present invention relates to the following 1) to 4).
1) A prophylactic or therapeutic agent for a neurodegenerative disease comprising as an active ingredient a fermented lactic acid bacterium of Yahata, or a fermented lactic acid bacterium of a herbal composition containing at least one selected from the seven ginsengs, Tochu, licorice and yellow spirit.
2) The preventive, ameliorating, or therapeutic agent for neurodegenerative diseases according to 1), wherein the plant lactic acid bacterium is at least one selected from Lactobacillus plantarum, Lactobacillus brevis, Pediococcus pentosaceus, and Lactobacillus reuteri.
3) The plant lactic acid bacteria is one or more selected from Lactobacillus plantarum SN13T strain, Lactobacillus plantarum SN35N strain, Pediococcus pentosaceus LP28 strain, Lactobacillus brevis 174A strain and Lactobacillus reuteri BM53-1 strain 1) Or a preventive, ameliorating or treating agent for neurodegenerative diseases.
4) The preventive or therapeutic agent for a neurodegenerative disease according to any one of 1) to 3), wherein the herbal medicine composition includes all of ginseng, ginseng, licorice and yellow spirit.
本発明の神経変性疾患の予防又は治療剤によれば、特定の神経細胞の変性、脱落を伴うアルツハイマー病、パーキンソン病等の予防、改善又は治療が可能となる。 According to the preventive or therapeutic agent for neurodegenerative diseases of the present invention, it becomes possible to prevent, improve or treat Alzheimer's disease, Parkinson's disease and the like accompanied by degeneration and loss of specific nerve cells.
本発明の植物乳酸菌発酵物は、「八朔（ハッサク）」又は「田七、杜仲、甘草及び黄精を含む生薬組成物」を植物乳酸菌で発酵させた発酵物である。 The plant lactic acid bacteria fermented product of the present invention is a fermented product obtained by fermenting “Hassaku” or “herbal medicine composition containing Tabana, Tochu, Licorice and Yellow Seyce” with plant lactic acid bacteria.
「八朔」は、広島県が原産で、和歌山県等で盛んに栽培されているミカン科の常緑高木であり、その学名は「Citrus hassaku Hort．」である。
乳酸菌発酵に供する部位は、果実、果皮等が挙げられるが、果実が好ましい。
“Yawata” is an evergreen Takagi of the citrus family that is native to Hiroshima Prefecture and is actively cultivated in Wakayama Prefecture, etc., and its scientific name is “Citrus hassaku Hort.”.
Examples of the site to be subjected to lactic acid bacteria fermentation include fruit and pericarp, but fruit is preferred.
本発明において、八朔は、ミキサー等を用いて摩砕し、必要に応じて発酵に適した形状、例えばピューレ状（果皮を含む）、搾汁、八朔抽出液（八朔を水等の抽出溶媒で抽出した液）、若しくはこれらの濃縮液、又は八朔の果皮を粉末化したものをそのまま、或いはこれらを蒸留水等で適当な濃度に希釈して発酵原料とすることができる。 In the present invention, Yawata is ground using a mixer or the like, and, if necessary, a shape suitable for fermentation, such as puree (including fruit skin), squeezed, Yawata extract (yawata with an extraction solvent such as water) Extracted liquids), or concentrated liquids thereof, or those obtained by pulverizing Yawata peels as they are, or these can be diluted to an appropriate concentration with distilled water or the like to obtain fermentation raw materials.
本発明において、田七人参、杜仲、甘草及び黄精から選ばれる１種以上を含有する生薬組成物（以下、「生薬組成物」とも称する）としては、田七人参、杜仲、甘草及び黄精の一種以上を組み合わせて用いることができるが、田七人参、杜仲、甘草及び黄精の４種を含むものが好ましい。田七人参、杜仲、甘草及び黄精を含む生薬組成物としては、好適には、組成物中に、田七を１０〜９０質量％、好ましくは３０〜９０質量％、杜仲を１０〜９０質量％、好ましくは１０〜７０質量％、より好ましくは４０〜９０質量％、甘草を４〜１５質量％、より好ましくは６〜１１重量％、黄精を４〜２０質量％、好ましくは６〜１２質量％を含有する組成物が挙げられ、さらに高麗人参（朝鮮人参）を５〜２０質量％含有するもの、さらには、蜂蜜を３０質量％以下で含むものが好適に例示される。より具体的には、田七５５質量％、杜仲２５質量％、黄精１０質量％、甘草５質量％、高麗人参３質量％、及び蜂蜜２質量％を含有する組成物が例示できる。 In the present invention, the herbal medicine composition (hereinafter also referred to as “herbal medicine composition”) containing at least one selected from Tannan ginseng, Tochu, licorice and yellow spirit is a kind of Tannin ginseng, Tochu, licorice and yellow spirit. Although the above can be used in combination, those containing four kinds of ginseng, ginseng, licorice and yellow spirit are preferred. As a herbal medicine composition containing ginseng, ginseng, licorice and yellow spirit, 10 to 90% by mass, preferably 30 to 90% by mass, and 10 to 90% by mass of ginseng in the composition. , Preferably 10 to 70% by weight, more preferably 40 to 90% by weight, licorice 4 to 15% by weight, more preferably 6 to 11% by weight, yellow spirit 4 to 20% by weight, preferably 6 to 12% by weight Preferred examples include those containing 5 to 20% by mass of ginseng (Ginseng), and further containing 30% by mass or less of honey. More specifically, there can be exemplified a composition containing 55% by mass of Tanada, 25% by mass of Tochu, 10% by mass of yellow spirit, 5% by mass of licorice, 3% by mass of ginseng, and 2% by mass of honey.
ここで、「田七人参」は、三七人参とも呼ばれ、中国原産のサンシチニンジン Panax pseudo-ginseng Wall.の根を、「杜仲」は、トチュウ科のトチュウ Eucommiae ulmoidesの樹皮の乾燥物を、「黄精」は、Polygonati Rhizoma又はSiberian Solomonseal Rhizomeとも称され、Polygonatum属の起源植物の根茎の乾燥物を、「甘草」は、マメ科のGlycyrrhiza属植物であるGlycyrrhiza glabra Linnの根及び走茎の乾燥物を、それぞれ意味する。 Here, “Tanachi Ginseng” is also called “Ginseng Ginseng”, the root of Panax pseudo-ginseng Wall., Which is native to China, and “Shunchu” is the dried bark of Eucommiae ulmoides. `` Yellow '' is also called Polygonati Rhizoma or Siberian Solomonseal Rhizome. Each means dry matter.
上記生薬組成物は、田七人参、杜仲、黄精及び甘草の各熱水抽出物を乾燥させたエキスに、適宜高麗人蔘エキスや蜂蜜を加えて混合し、粉末状又は粉末顆粒状とすることにより調製することができる。
本発明の生薬組成物としては、田七人参、杜仲、黄精及び甘草を含有する市販の「養生片仔廣（登録商標）」（株式会社 協通事業）を用いることもできる。
The above herbal composition should be powdered or granulated by adding ginseng extract or honey as appropriate to the dried extract of hot water extract of ginseng, Tochu, yellow spirit and licorice. Can be prepared.
As the herbal medicine composition of the present invention, commercially available “cured cocoon candy (registered trademark)” (Kyoto Business Co., Ltd.) containing ginseng, ginseng, yellow spirit and licorice can also be used.
本発明において、植物乳酸菌とは植物由来の乳酸菌をいい、例えば穀物、野菜、果物、あるいはこれらを原材料に含む発酵食品から分離されたものを使用することができる。具体的には、ラクトバチルス プランタラムＳＮ１３Ｔ株（分離源：ソーセージ）、ラクトバチルス プランタラムＳＮ２６Ｔ株（分離源：ソーセージ）、ラクトバチルス プランタラムＳＮ３５Ｎ株（分離源：ナシ）、ラクトバチルス プランタラムＪＣＭ １１４９株（分離源：塩漬キャベツ）、ラクトバチルス プランタラムＪＣＭ ８３４８株（分離源：コメ）、ラクトバチルス プランタラムＩＦＯ３０７０株（ＪＣＭ １０５７株）、ラクトバチルス カゼイＫ−１株（分離源：亀田 植物乳酸菌ヨーグルト）、ラクトバチルス カゼイＪＣＭ ８１３６株（分離源：不明）、ペディオコッカス ペントサセウス（分離源：大塚 野菜の戦士）、ペディオコッカス ペントサセウスＬＰ２８株（分離源：ロンガン）、ペディオコッカスＪＣＭ ５８８５株（分離源：酒もろみ）、ラクトバチルス プランタラムＳＮ３５Ｍ株（分離源：メロン）、ラクトコッカス ラクティス サブスペシース ラクティス ＳＮ２６Ｎ株（分離源：ナシ）、エンテロコッカス スペシースＳＮ２１Ｉ株（分離源：イチジク）及びエンテロコッカス ムンヅティＳＮ２９Ｎ株（分離源：ナシ）ラクトバチルス ブレビス１７４Ａ株（分離源：伊予柑 ＮＩＴＥ ＡＰ−００２２４７）のほか、ラクトバチルス ヒルガルディＮＢＲＣ１５８８６（分離源：ワイン）等が挙げられ、このうち、ラクトバチルス プランタラム、ラクトバチルス ブレビス、ペディオコッカス ペントサセウス、ラクトバチルス ロイテリＢＭ５３−１（ＮＩＴＥ Ｐ−０２１２８）が好ましい。
中でも、本発明者により分離され、独立行政法人産業技術総合研究所特許生物寄託センターへ寄託されている、ラクトバチルス プランタラムＳＮ１３Ｔ株(ＮＩＴＥ Ｐ−７)、ラクトバチルス プランタラムＳＮ３５Ｎ株(ＮＩＴＥ Ｐ−６)、ディオコッカス ペントサセウスＬＰ２８株（ＮＩＴＥ ＢＰ−７００）及びラクトバチルス ブレビス１７４Ａ株 （ＮＩＴＥ ＡＰ−００２２４７）、ラクトバチルス ロイテリＢＭ５３−１（ＮＩＴＥ Ｐ−０２１２６）がより好ましい。
In the present invention, a plant lactic acid bacterium refers to a plant-derived lactic acid bacterium, such as cereals, vegetables, fruits, or those isolated from fermented foods containing these as raw materials. Specifically, Lactobacillus plantarum SN13T strain (separation source: sausage), Lactobacillus plantarum SN26T strain (separation source: sausage), Lactobacillus plantarum SN35N strain (separation source: pear), Lactobacillus plantarum JCM 1149 Strain (source: salted cabbage), Lactobacillus plantarum JCM 8348 strain (source: rice), Lactobacillus plantarum IFO 3070 strain (JCM 1057 strain), Lactobacillus casei K-1 strain (source: Kameda plant lactic acid bacteria Yogurt), Lactobacillus casei JCM 8136 strain (source: unknown), Pediococcus pentosaceus (source: Otsuka vegetable warrior), Pediococcus pentosaceus LP28 strain (source: Longan), Pediococcus JCM 5858 (Segregation source: Sake moromi), Lactobacillus plantarum SN35M strain (Separation source: Melon), Lactococcus lactis subspecies lactis SN26N strain (separation source: pear), Enterococcus speces SN21I strain (separation source: fig) and Enterococcus munsii SN29N Strain (source: pear) Lactobacillus brevis 174A strain (source: Iyokan NITE AP-002247), Lactobacillus hirugardi NBRC15886 (separation source: wine) and the like, among which Lactobacillus plantarum, lacto Bacillus brevis, Pediococcus pentosaceus, Lactobacillus reuteri BM53-1 (NITE P-02128) are preferred.
Among them, the Lactobacillus plantarum SN13T strain (NITE P-7), the Lactobacillus plantarum SN35N strain (NITE P-), which have been isolated by the present inventor and deposited at the National Institute of Advanced Industrial Science and Technology (AIST). 6), Diococcus pentosaceus LP28 strain (NITE BP-700), Lactobacillus brevis 174A strain (NITE AP-002247), and Lactobacillus reuteri BM53-1 (NITE P-02126) are more preferable.
八朔や生薬組成物に植物乳酸菌を接種する方法は特に制限されず、例えば上記の発酵に適した形状にした八朔や生薬組成物に菌体を混合する方法、発酵に適した形状の八朔や生薬組成物を溶解又は懸濁した水に菌体を混合する方法、菌体を適当な液体培地（例えば、ＭＲＳ培地）で培養した培養液を、発酵に適した形状の八朔や生薬組成物に接触させる方法、発酵に適した形状の八朔や生薬組成物を溶解又は懸濁した上記液体培地で植物乳酸菌を培養する方法などである。ここで、培養に際しては、酒粕を添加するのが当該植物乳酸菌の増殖を促進させる点から好ましい。特に八朔の植物乳酸菌発酵物を製造する場合には、酒粕の存在下で培養することが必要である。酒粕の添加量は、培地中に好ましくは０．０１〜５質量％、より好ましくは０．０５〜２質量％、さらに好ましくは０．０５〜１質量％である。 The method of inoculating the plant lactic acid bacteria into the yam or the herbal medicine composition is not particularly limited. A method of mixing cells in water in which the composition is dissolved or suspended, and contacting a culture solution obtained by culturing the cells in an appropriate liquid medium (for example, MRS medium) with a yam or a herbal medicine composition in a shape suitable for fermentation And a method of cultivating plant lactic acid bacteria in the above liquid medium in which a yam or a herbal composition having a shape suitable for fermentation is dissolved or suspended. Here, in culturing, it is preferable to add sake lees to promote the growth of the plant lactic acid bacteria. In particular, when producing a fermented lactic acid bacterium of Yawata, it is necessary to culture in the presence of sake lees. The amount of sake lees added in the medium is preferably 0.01 to 5% by mass, more preferably 0.05 to 2% by mass, and still more preferably 0.05 to 1% by mass.
発酵に際しては、植物乳酸菌の一白金耳を種培養培地に接種することにより所定時間培養して種培養液とするが、本培養では本培養培地容量に対して１％〜２％程度の種培養液を接種後、３０〜４５℃の温度で１２〜７２時間、好ましくは１０時間〜３６時間培養することで乳酸菌発酵液を得る。発酵過程では発酵液のｐＨが徐々に低下するが、ｐＨが４．５以下になるまで発酵させることが好ましく、４．２以下がより好ましい。また、発酵は、好気発酵、嫌気発酵のいずれでも可能であり、好ましくは嫌気発酵である。好気発酵の場合には撹拌発酵よりも静置発酵が好ましい。
得られた発酵物は、必要に応じて加熱殺菌（通常、６０〜８５℃で２〜６０分間）した後、そのまま用いることができるが、遠心分離等の手段により、該発酵物から不溶物を除去して、その上清を用いることもできる。さらに、ろ過により菌体等を除いた上清を用いることもできる。
During fermentation, a platinum loop of plant lactic acid bacteria is inoculated into a seed culture medium and cultured for a predetermined time to obtain a seed culture solution. In the main culture, the seed culture is about 1% to 2% with respect to the main culture medium volume. After inoculating the solution, a lactic acid bacteria fermentation solution is obtained by culturing at a temperature of 30 to 45 ° C. for 12 to 72 hours, preferably 10 to 36 hours. In the fermentation process, the pH of the fermentation solution gradually decreases, but it is preferably fermented until the pH reaches 4.5 or less, more preferably 4.2 or less. Moreover, fermentation can be carried out by either aerobic fermentation or anaerobic fermentation, preferably anaerobic fermentation. In the case of aerobic fermentation, stationary fermentation is preferable to stirring fermentation.
The obtained fermented product can be used as it is after sterilization by heating (usually 2 to 60 minutes at 60 to 85 ° C.) as necessary, but insoluble matter is removed from the fermented product by means such as centrifugation. The supernatant can be used after removal. Furthermore, a supernatant obtained by removing cells by filtration can be used.
斯くして得られる本発明の植物乳酸菌発酵物は、後記実施例に示すように、ラット由来のＰＣ−１２細胞における神経突起の形成を促進することから、神経新生促進作用及び／又は神経再生促進作用を有すると考えられる。したがって、本発明の植物乳酸菌発酵物は、神経変性疾患の予防又は治療剤となり得、神経変性疾患の予防又は治療のために使用することができる。神経変性疾患の予防又は治療剤は、神経変性疾患の予防又は治療に有効な医薬品又は食品として、又は医薬品又は食品に配合する素材として使用可能である。
ここで、食品は、神経変性疾患の予防又は改善をコンセプトとし、その旨を表示した保険機能食品、例えば機能性表示食品、特定保健用食品、栄養機能食品等とすることが可能である。
Since the plant lactic acid bacteria fermented product of the present invention thus obtained promotes neurite formation in rat-derived PC-12 cells as shown in the Examples below, it promotes neurogenesis and / or promotes nerve regeneration. It is considered to have an action. Therefore, the plant lactic acid bacteria fermented product of the present invention can be a preventive or therapeutic agent for neurodegenerative diseases and can be used for the prevention or treatment of neurodegenerative diseases. The preventive or therapeutic agent for a neurodegenerative disease can be used as a drug or food effective for the prevention or treatment of a neurodegenerative disease or as a material to be blended in a drug or food.
Here, the food is based on the concept of prevention or improvement of a neurodegenerative disease, and can be an insurance functional food that indicates the fact, such as a functional display food, a food for specified health use, a nutritional functional food, or the like.
本発明において、「神経変性疾患」としては、特定の神経細胞の変性、脱落に基づく神経回路網の破綻により引き起こされる病態をいい、例えば、アルツハイマー病、パーキンソン病、筋萎縮性側索硬化症、小脳性運動失調症、脊髄性筋萎縮症、進行性核上麻痺、ハンチントン病等を挙げることができる。 In the present invention, the “neurodegenerative disease” refers to a condition caused by the degeneration of specific nerve cells, the breakdown of the neural network based on loss, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Cerebellar ataxia, spinal muscular atrophy, progressive supranuclear palsy, Huntington's disease and the like.
本発明の植物乳酸菌発酵物を含む医薬品として用いる場合の投与形態としては、例えば錠剤、カプセル剤、顆粒剤、散剤、シロップ剤等による経口投与又は注射剤、坐剤、吸入薬、経皮吸収剤、外用剤等による非経口投与が挙げられるが、好ましい形態は経口投与である。
このような種々の剤型の医薬製剤は、本発明の植物乳酸菌発酵物の作用を妨げない範囲で、他の薬学的に許容される賦形剤、結合剤、増量剤、崩壊剤、界面活性剤、滑沢剤、分散剤、緩衝剤、保存剤、嬌味剤、香料、被膜剤、担体、希釈剤等を適宜組み合わせることにより調製できる。
Examples of the dosage form when used as a pharmaceutical product containing the plant lactic acid bacteria fermented product of the present invention include oral administration such as tablets, capsules, granules, powders, and syrups, or injections, suppositories, inhalants, and transdermal absorption agents. In addition, parenteral administration by an external preparation or the like can be mentioned, but a preferred form is oral administration.
Such pharmaceutical preparations of various dosage forms can be used for other pharmaceutically acceptable excipients, binders, extenders, disintegrants, surfactants, as long as they do not interfere with the action of the fermented plant lactic acid bacteria of the present invention. It can be prepared by appropriately combining agents, lubricants, dispersants, buffers, preservatives, flavoring agents, fragrances, coating agents, carriers, diluents and the like.
また、本発明の植物乳酸菌発酵物を含む食品の形態としては、果汁又は野菜汁飲料、炭酸飲料、茶系飲料、乳飲料、発酵乳、発酵果汁、発酵野菜汁、アルコール飲料、清涼飲料等の飲料や、ゼリー状食品や各種スナック類、焼き菓子、ケーキ類、チョコレート、ジャム、パン、ガム、飴、スープ類、漬物、佃煮などの各種食品組成物の他、サプリメントの如く上述した経口投与製剤と同様の形態（錠剤、カプセル剤、シロップ等）が挙げられる。 Moreover, as a form of food containing the plant lactic acid bacteria fermented product of the present invention, fruit juice or vegetable juice beverage, carbonated beverage, tea-based beverage, milk beverage, fermented milk, fermented fruit juice, fermented vegetable juice, alcoholic beverage, soft drink, etc. In addition to various food compositions such as beverages, jelly-like foods, various snacks, baked goods, cakes, chocolate, jam, bread, gum, rice cakes, soups, pickles, boiled foods, orally administered preparations as described above like supplements And the like (tablets, capsules, syrups, etc.).
上記医薬品や食品における本発明の植物乳酸菌発酵物の含有量は、特に限定されず一日投与量等に合わせて適宜調節すれば良い。一例として、経口投与用製剤として用いる場合の該製剤中の含有量は、乾燥固形分として０．０１〜５０重量％、好ましくは０．０５〜１０重量％が良い。 The content of the fermented plant lactic acid bacteria of the present invention in the above pharmaceuticals and foods is not particularly limited, and may be appropriately adjusted according to the daily dose. As an example, when used as a preparation for oral administration, the content in the preparation is 0.01 to 50% by weight, preferably 0.05 to 10% by weight as a dry solid content.
上記医薬品や食品の摂取又は投与対象者としては、神経機能の低下した者、神経機能低下のリスクが高い者、例えばアルツハイマー病の患者、アルツハイマー病の疑いがある患者等が挙げられる。 Examples of the subjects of intake or administration of the above-mentioned pharmaceuticals and foods include those who have reduced nerve function, those who have a high risk of nerve function reduction, such as patients with Alzheimer's disease and patients suspected of having Alzheimer's disease.
本発明の神経変性疾患の予防又は改善剤は、１日１回又は数回に分けて投与することができ、投与量は特に制限されない。
以下、本発明を具体的に説明するが、本発明は下記の例に限定されるものではない。
The agent for preventing or ameliorating a neurodegenerative disease of the present invention can be administered once or several times a day, and the dosage is not particularly limited.
Hereinafter, the present invention will be specifically described, but the present invention is not limited to the following examples.
製造例１ 八朔の植物乳酸菌発酵物の調製
八朔濃縮果汁（株式会社ヒロシマ・コープ、広島県三原市）をBrix 17.0に合わせ、炭酸水素ナトリウムでpH5.2に調整した。その後、1% になるよう酒粕粉末を加え、100℃で10分間の熱処理により殺菌した。 準備した本培養培地に以下に示す植物乳酸菌株の前培養液を1%になるように加え、37℃で48時間の静置培養を行った。培養終了後、培養液を遠心し、その培養液上清を5N NaOHでpH5.5に調整後、フィルター殺菌したものを、八朔の植物乳酸菌発酵物として得た。
Production Example 1 Preparation of Yawata Plant Lactic Acid Bacteria Fermented Product Yawata concentrated fruit juice (Hiroshima Corp., Mihara City, Hiroshima Prefecture) was adjusted to Brix 17.0 and adjusted to pH 5.2 with sodium bicarbonate. Thereafter, sake lees powder was added to 1% and sterilized by heat treatment at 100 ° C. for 10 minutes. To the prepared main culture medium, a pre-culture solution of the plant lactic acid bacterial strain shown below was added to 1%, and stationary culture was performed at 37 ° C. for 48 hours. After completion of the culture, the culture broth was centrifuged, and the supernatant of the culture broth was adjusted to pH 5.5 with 5N NaOH and then sterilized with a filter to obtain a fermented lactic acid bacterium of Yawata.
植物乳酸菌：ラクトバチルス プランタラムＳＮ１３Ｔ株、ラクトバチルス プランタラムＳＮ３５Ｎ株、ぺディオコッカス ペントサセウスＬＰ２８株及びラクトバチルス ブレビス１７４Ａ株、ラクトバチルス ロイテリ ＢＭ５３−１株 Plant lactic acid bacteria: Lactobacillus plantarum SN13T strain, Lactobacillus plantarum SN35N strain, Pediococcus pentosaceus LP28 strain and Lactobacillus brevis 174A strain, Lactobacillus reuteri BM53-1 strain
製造例２ 田七人参、杜仲、甘草及び黄精の４種を含む生薬組成物「養生片仔廣（登録商標）の植物乳酸菌発酵物の調製
「養生片仔廣（登録商標）」（株式会社 協通事業製；「ＹＨＫ」と略す」）のタブレット錠剤（0.25g重量/ 錠）を乳鉢ですり潰し、得られた粉末を20 (w/v) % となるよう蒸留水に懸濁し、60℃で, 4時間, 撹拌した。得られた懸濁液を遠心し、その上清を5% になるようMRS培地に加え, 121℃, 15分間の熱処理により殺菌した。これを培地として以下に示す植物乳酸菌株の前培養液（スターター）を1%になるように加え, 37℃, 48時間の静置培養を行った。培養終了後、培養液を遠心し、その培養液上清を5N NaOHでpH5.5に調整後、フィルター（0.22 μｍ 直径, アドバンテック）で濾過滅菌したものを生薬組成物の植物乳酸菌発酵物として得た。
Production Example 2 Preparation of Fermented Plant Lactic Acid Bacteria of Cured Kappo Koji (Registered Trademark) “Kyoju Kappa Koji (Registered Trademark)” (Kyoto Business Co., Ltd.) (Abbreviated as “YHK”)) is crushed in a mortar and the resulting powder is suspended in distilled water to a concentration of 20 (w / v)% at 60 ° C., 4 Stir for hours. The obtained suspension was centrifuged, and the supernatant was added to MRS medium to 5% and sterilized by heat treatment at 121 ° C. for 15 minutes. Using this as a medium, the following pre-culture solution (starter) of the plant lactic acid strain was added to 1%, and stationary culture was performed at 37 ° C. for 48 hours. After completion of the culture, the culture solution is centrifuged, and the culture supernatant is adjusted to pH 5.5 with 5N NaOH and then sterilized by filtration with a filter (0.22 μm diameter, Advantech) to obtain a plant lactic acid bacteria fermentation product of the herbal medicine composition. It was.
植物乳酸菌：ラクトバチルス プランタラムＳＮ１３Ｔ株、ラクトバチルス プランタラムＳＮ３５Ｎ株、ディオコッカス ペントサセウスＬＰ２８株及びラクトバチルス ブレビス１７４Ａ株、ラクトバチルス ロイテリ ＢＭ５３−１株 Plant lactic acid bacteria: Lactobacillus plantarum SN13T strain, Lactobacillus plantarum SN35N strain, Diococcus pentosaceus LP28 strain and Lactobacillus brevis 174A strain, Lactobacillus reuteri BM53-1 strain
試験例１ 神経突起形成促進作用
１．方法
ラット副腎髄質褐色腫由来細胞（ＰＣ−１２細胞）の培養には、10%FBS及び抗生物質（ペニシリンおよびストレプトマイシン）を含有するDMEMを用いた。100 mm 組織培養皿 (Falcon) に PC-12 細胞を播種した後，CO2 インキュベーターを用い、 37℃，5% CO2条件下で培養した． なお、3日に一度、 Trypsin-EDTA 処理して継代した。さらに、神経突起形成実験には、PC12細胞を、6ｘ105 cells/well になるように24-ウェルプレートへ播種し、24 時間培養した。培養終了後、培養液を除去し、1% FBS/ DMEM を加え6−8時間スタベーションを行った。そのあと、製造例１で調製した八朔の植物乳酸菌発酵物及び未発酵のサンプル（乳酸菌を接種しない八朔果汁）、製造例２で調製した生薬組成物の植物乳酸菌発酵物及び未発酵のサンプル（乳酸菌を接種しなかった培地のみ）を最終濃度5%になるよう加え、さらに4-5日間培養した。
Test Example 1 Neurite formation promoting action Method DMEM containing 10% FBS and antibiotics (penicillin and streptomycin) was used for culture of rat adrenal medulla melanoma-derived cells (PC-12 cells). After seeding PC-12 cells in a 100 mm tissue culture dish (Falcon), the cells were cultured using a CO 2 incubator at 37 ° C and 5% CO 2 . In addition, it was passaged by Trypsin-EDTA treatment once every 3 days. Furthermore, in the neurite formation experiment, PC12 cells were seeded in a 24-well plate at 6 × 10 5 cells / well and cultured for 24 hours. After completion of the culture, the culture solution was removed, 1% FBS / DMEM was added, and starvation was performed for 6 to 8 hours. Thereafter, the fermented lactic acid bacteria and unfermented samples of Yahata prepared in Production Example 1, the fermented plant lactic acid bacteria of the herbal medicine composition prepared in Production Example 2, and the unfermented samples (lactic acid bacteria) Was added to a final concentration of 5% and further cultured for 4-5 days.
２．結果
図１（１）の写真のように, ラクトバチルス プランタルム ＳＮ３５Ｎ株をＭＲＳ培地で培養し, 得られた培養液上清は, PC-12細胞の突起形成を引き起こさない。また、図１（２）のようにＹＨＫを含むMRS培地（乳酸菌培養なし）、及び図１（４）のように八朔果汁（乳酸菌培養なし）にはPC-12細胞の突起形成能は存在しない。
しかしながら、ＹＨＫの植物乳酸菌（ＳＮ３５Ｎ株）発酵物（図１（３））や、八朔果汁の植物乳酸菌（ＳＮ３５Ｎ株）発酵物（図１（５））ではＰＣ−１２細胞の突起形成を著しい促進が認められた。
尚、図１には、ラクトバチルス プランタルム ＳＮ３５Ｎ株を用いて発酵した発酵物の結果を示したが、製造例１及び２で示した植物乳酸菌株を用いた発酵物にはいずれも突起形成促進効果が認められ、そのうち、ラクトバチルス プランタルム ＳＮ３５Ｎ株とペディオコッカス ペントサセウス ＬＰ２８株はより効果が高かった。
2. Results As shown in the photograph of FIG. 1 (1), Lactobacillus plantarum SN35N strain was cultured in MRS medium, and the obtained culture supernatant did not cause PC-12 cell protrusion formation. Moreover, the projection formation ability of PC-12 cells does not exist in the MRS medium (without lactic acid bacteria culture) containing YHK as shown in FIG. 1 (2) and the Yahata fruit juice (without lactic acid bacteria culture) as shown in FIG. 1 (4). .
However, YHK plant lactic acid bacteria (SN35N strain) fermented product (FIG. 1 (3)) and Yawata fruit juice plant lactic acid bacteria (SN35N strain) fermented product (FIG. 1 (5)) remarkably promote the formation of protrusions of PC-12 cells. Was recognized.
In addition, in FIG. 1, although the result of the fermented material fermented using the Lactobacillus plantarum SN35N strain | stump | stock was shown, all the fermented products using the plant lactic acid strain shown in manufacture example 1 and 2 have a projection formation promotion effect. Among them, Lactobacillus plantarum SN35N strain and Pediococcus pentosaceus LP28 strain were more effective.
実施例２ 神経突起誘導能促進作用
１．方法
neurogenin-1は転写調節因子の１つであり、この発現量が多ければ神経突起誘導能が高いと判断できる。そこで、定量ＰＣＲ（Ｑ−ＰＣＲ）を用いて、neurogenin-1の発現量を測定した。すなわち、製造例２と同様に、ＹＨＫを添加したＭＲＳ培地で３種類の植物乳酸菌（Lb. brevis 174A; Lb. plantarum SN35N; P. pentosaceus LP28)を培養し、得られた各培養液上清（YHKの植物乳酸菌発酵物）をＰＣ−１２培養細胞に添加し、その神経細胞で発現するneurogenin-1をQ-PCRで定量した。
Example 2 Neurite inducing ability promoting action Method
Neurogenin-1 is one of the transcriptional regulatory factors, and if this expression level is large, it can be judged that neurite inducing ability is high. Therefore, the expression level of neurogenin-1 was measured using quantitative PCR (Q-PCR). That is, in the same manner as in Production Example 2, three types of plant lactic acid bacteria (Lb. brevis 174A; Lb. plantarum SN35N; P. pentosaceus LP28) were cultured in MRS medium supplemented with YHK. YHK plant lactic acid bacteria fermented product) was added to PC-12 cultured cells, and neurogenin-1 expressed in the neurons was quantified by Q-PCR.
２．結果
未醗酵のＹＨＫ含有培地のみを添加した場合におけるＰＣ−１２細胞のneurogenin-1転写量を１としたときの、３種の各乳酸菌によるＹＨＫの発酵物を添加した際に誘導されるneurogenin-1転写量を図２に示した。
その結果、何れの植物乳酸菌発酵物においてもneurogenin-1の発現量が増加したが、特にＬＰ２８による発酵物においてneurogenin-1の発現量が高かった。
2. Results Neurogenin- induced when the fermentation of YHK by each of the three types of lactic acid bacteria is added, assuming that the amount of neurogenin-1 transcription of PC-12 cells is 1 when only unfermented YHK-containing medium is added. One transfer amount is shown in FIG.
As a result, the expression level of neurogenin-1 increased in any fermented lactic acid bacteria of the plant, but the expression level of neurogenin-1 was particularly high in the fermented material by LP28.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2016119085A JP6898628B2 (en) | 2016-06-15 | 2016-06-15 | Neurodegenerative disease therapeutic agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2016119085A JP6898628B2 (en) | 2016-06-15 | 2016-06-15 | Neurodegenerative disease therapeutic agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2017222601A true JP2017222601A (en) | 2017-12-21 |
| JP6898628B2 JP6898628B2 (en) | 2021-07-07 |
Family
ID=60686249
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016119085A Active JP6898628B2 (en) | 2016-06-15 | 2016-06-15 | Neurodegenerative disease therapeutic agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP6898628B2 (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019011305A (en) * | 2016-08-25 | 2019-01-24 | 心範 謝 | Crude drug composition used for preventing or treating dementia or neurodegenerative diseases |
| JP2019178123A (en) * | 2018-03-30 | 2019-10-17 | 丸善製薬株式会社 | Glycyrrhiza extract fermented product, whitening agent, anti-aging agent, skin cosmetic and food and drink |
| JP2021004214A (en) * | 2019-06-27 | 2021-01-14 | 株式会社再春館製薬所 | Combinational fermented product |
| WO2021015288A1 (en) * | 2019-07-24 | 2021-01-28 | 雪印メグミルク株式会社 | Composition for maintenance and/or improvement of memory/learning ability, and food, medicine and feed each containing said composition |
| CN112841641A (en) * | 2021-01-26 | 2021-05-28 | 宁波健安进生物科技有限公司 | Instant polygonatum sibiricum crisp chips and preparation method thereof |
| CN114786693A (en) * | 2019-12-02 | 2022-07-22 | 生活质量研究所 | Agent for preventing or improving orthostatic hypotension and composition containing same |
| US11602552B2 (en) * | 2018-02-02 | 2023-03-14 | Kobiolabs, Inc. | Lactobacillus plantarum KBL396 strain and use thereof |
| US11660319B2 (en) | 2017-06-14 | 2023-05-30 | 4D Pharma Research Limited | Compositions comprising bacterial strains |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996009061A1 (en) * | 1994-09-19 | 1996-03-28 | Yukinari Kaya | Antiinfective agent, cerebral metabolism activator, and process for producing the same |
| JP2000139405A (en) * | 1998-11-13 | 2000-05-23 | Shinhan Sha | Food additive and health food |
| JP2005526077A (en) * | 2002-03-15 | 2005-09-02 | サマリタン・ファーマシューティカルズ・インコーポレイテッド | Neuroprotective spirostenol pharmaceutical composition |
| JP2006117588A (en) * | 2004-10-22 | 2006-05-11 | Shinhan Sha | Crude medicine composition |
| JP2006526008A (en) * | 2003-05-19 | 2006-11-16 | ホングリム トレーディング カンパニー リミテッド | Composition for protecting brain cells containing ginsenoside Rh2 as an active ingredient |
| WO2008155999A1 (en) * | 2007-06-21 | 2008-12-24 | Nagase & Co., Ltd. | Gabaergic neuron activator |
| JP2011012048A (en) * | 2009-06-03 | 2011-01-20 | Fuji Sangyo Kk | Koji mold-fermented composition of citrus fruit rind |
| JP2014111664A (en) * | 2010-02-26 | 2014-06-19 | Kotaro Kanpo Seiyaku Kk | Dried plant tissue and plant tissue extract for ameliorating central nervous system degenerative diseases accompanied by learning/memory disorders, movement disorders and the like, and pharmaceutical agent and food comprising the same |
| KR20140094962A (en) * | 2013-01-23 | 2014-07-31 | 계명대학교 산학협력단 | Composition Comprising Licochalcone A for prevention or treatment of Neurodegenarative Diseases |
| JP2015526085A (en) * | 2012-08-16 | 2015-09-10 | ユニバーシティ−インダストリー コオペレーション グループ オブ キョン ヒ ユニバーシティＵｎｉｖｅｒｓｉｔｙ−Ｉｎｄｕｓｔｒｙ Ｃｏｏｐｅｒａｔｉｏｎ Ｇｒｏｕｐ Ｏｆ Ｋｙｕｎｇ Ｈｅｅ Ｕｎｉｖｅｒｓｉｔｙ | Lactic acid bacteria having preventive and / or therapeutic activity for aging and dementia |
-
2016
- 2016-06-15 JP JP2016119085A patent/JP6898628B2/en active Active
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996009061A1 (en) * | 1994-09-19 | 1996-03-28 | Yukinari Kaya | Antiinfective agent, cerebral metabolism activator, and process for producing the same |
| JP2000139405A (en) * | 1998-11-13 | 2000-05-23 | Shinhan Sha | Food additive and health food |
| JP2005526077A (en) * | 2002-03-15 | 2005-09-02 | サマリタン・ファーマシューティカルズ・インコーポレイテッド | Neuroprotective spirostenol pharmaceutical composition |
| JP2006526008A (en) * | 2003-05-19 | 2006-11-16 | ホングリム トレーディング カンパニー リミテッド | Composition for protecting brain cells containing ginsenoside Rh2 as an active ingredient |
| JP2006117588A (en) * | 2004-10-22 | 2006-05-11 | Shinhan Sha | Crude medicine composition |
| WO2008155999A1 (en) * | 2007-06-21 | 2008-12-24 | Nagase & Co., Ltd. | Gabaergic neuron activator |
| JP2011012048A (en) * | 2009-06-03 | 2011-01-20 | Fuji Sangyo Kk | Koji mold-fermented composition of citrus fruit rind |
| JP2014111664A (en) * | 2010-02-26 | 2014-06-19 | Kotaro Kanpo Seiyaku Kk | Dried plant tissue and plant tissue extract for ameliorating central nervous system degenerative diseases accompanied by learning/memory disorders, movement disorders and the like, and pharmaceutical agent and food comprising the same |
| JP2015526085A (en) * | 2012-08-16 | 2015-09-10 | ユニバーシティ−インダストリー コオペレーション グループ オブ キョン ヒ ユニバーシティＵｎｉｖｅｒｓｉｔｙ−Ｉｎｄｕｓｔｒｙ Ｃｏｏｐｅｒａｔｉｏｎ Ｇｒｏｕｐ Ｏｆ Ｋｙｕｎｇ Ｈｅｅ Ｕｎｉｖｅｒｓｉｔｙ | Lactic acid bacteria having preventive and / or therapeutic activity for aging and dementia |
| KR20140094962A (en) * | 2013-01-23 | 2014-07-31 | 계명대학교 산학협력단 | Composition Comprising Licochalcone A for prevention or treatment of Neurodegenarative Diseases |
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019011305A (en) * | 2016-08-25 | 2019-01-24 | 心範 謝 | Crude drug composition used for preventing or treating dementia or neurodegenerative diseases |
| JP7005825B2 (en) | 2016-08-25 | 2022-02-10 | 株式会社協通事業 | Herbal composition for the prevention or treatment of dementia or neurodegenerative diseases |
| US11779613B2 (en) | 2017-06-14 | 2023-10-10 | Cj Bioscience, Inc. | Compositions comprising a bacterial strain of the genus Megasphera and uses thereof |
| US11660319B2 (en) | 2017-06-14 | 2023-05-30 | 4D Pharma Research Limited | Compositions comprising bacterial strains |
| US11602552B2 (en) * | 2018-02-02 | 2023-03-14 | Kobiolabs, Inc. | Lactobacillus plantarum KBL396 strain and use thereof |
| JP2019178123A (en) * | 2018-03-30 | 2019-10-17 | 丸善製薬株式会社 | Glycyrrhiza extract fermented product, whitening agent, anti-aging agent, skin cosmetic and food and drink |
| JP7458660B2 (en) | 2018-03-30 | 2024-04-01 | 丸善製薬株式会社 | Profilaggrin mRNA expression promoter, serine palmitoyltransferase mRNA expression promoter, and hyaluronic acid synthase 3 mRNA expression promoter |
| JP2022125278A (en) * | 2018-03-30 | 2022-08-26 | 丸善製薬株式会社 | PROFILAGGRIN mRNA EXPRESSION PROMOTER, SERINE PALMITOYL TRANSFERASE mRNA EXPRESSION PROMOTER, HYALURONIC ACID SYNTHASE 3 mRNA EXPRESSION PROMOTER, AND ANTI-AGING AGENT |
| JP7153899B2 (en) | 2018-03-30 | 2022-10-17 | 丸善製薬株式会社 | Whitening agents and skin cosmetics |
| JP2021004214A (en) * | 2019-06-27 | 2021-01-14 | 株式会社再春館製薬所 | Combinational fermented product |
| WO2021015288A1 (en) * | 2019-07-24 | 2021-01-28 | 雪印メグミルク株式会社 | Composition for maintenance and/or improvement of memory/learning ability, and food, medicine and feed each containing said composition |
| CN114786693A (en) * | 2019-12-02 | 2022-07-22 | 生活质量研究所 | Agent for preventing or improving orthostatic hypotension and composition containing same |
| CN112841641B (en) * | 2021-01-26 | 2022-03-15 | 宁波健安进生物科技有限公司 | Instant polygonatum sibiricum crisp chips and preparation method thereof |
| CN112841641A (en) * | 2021-01-26 | 2021-05-28 | 宁波健安进生物科技有限公司 | Instant polygonatum sibiricum crisp chips and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP6898628B2 (en) | 2021-07-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6898628B2 (en) | Neurodegenerative disease therapeutic agent | |
| JP6630388B2 (en) | Lactobacillus plantarum TCI378 and its use in reducing fat and improving gastrointestinal function | |
| KR20050109985A (en) | Antiallergic composition | |
| KR101252639B1 (en) | Composition for Prevention or Treatment of Osteoporosis Comprising Ssanghwatang and Fermentation Product Thereof with Lactic Acid Bacteria | |
| KR101778839B1 (en) | Pharmaceutical composition for preventing or treating dementia comprising an fermented extract of aronia | |
| KR20150110378A (en) | Composition comprising extract post-fermented tea | |
| KR101851195B1 (en) | Fermented mulberry leaves, femented mulberry leaves extract and use there of | |
| KR20230005057A (en) | Anti-aging composition using combination therapy comprising Lactobacilli us sp. and oriental medicine | |
| KR101709281B1 (en) | Composition for Prevention or Treatment of Osteoporosis Comprising Herbal Extract and Fermentation Product thereof with Lactic acid Bacteria | |
| KR102302933B1 (en) | Preparation of fermented garlic mixture and manufacturing method of composition effective for cardiovascular disease | |
| JP6458059B2 (en) | Composition for improving constipation, treating or preventing constipation comprising fermented lactic acid bacteria as active ingredient and method for producing the same | |
| KR20200008977A (en) | Composition for preventing, treating sarcopenia or muscle strengthening containing a fermented soybean | |
| KR102420930B1 (en) | Composition for preventing and treating of obesity comprising powder of lactic acid cell lysate | |
| KR101950969B1 (en) | Composition with Yak-Kong soybean (Glycine max) fermented by lactic acid bacteria for protecting brain neuronal cells and improving memory | |
| TWI734322B (en) | Kimchi for prevention or treatment of disease related to helicobacter pylori | |
| KR102275055B1 (en) | Composition comprising scutellaria alpina extract | |
| KR20160060834A (en) | Compositions for culture media of Kefir grain comprising plant extract and compositions for improving skin conditions comprising fermented products using the same | |
| KR101683030B1 (en) | A composition comprising the extract of fermented Curcuma longa L. and the compound extracted therefrom for preventing and treatment of cancer | |
| KR20230095471A (en) | Composition for improving muscle strength comprising fermented Schisandra chinensis fruit byproduct and method for preparing the same | |
| KR101973514B1 (en) | Prebiotics Containing Grape seed flour | |
| KR101608502B1 (en) | Composition for prevention or treatment of cardiovascular diseases comprising fermentation product of garlic | |
| KR101577732B1 (en) | Pharmaceutical composition comprising ferment of Phellodendron amurensis as an active ingredient for prevention or treatment of metabolic bone disease or climacteric disease | |
| KR20170029103A (en) | Food composition comprising fermented herb extract for preventing or improving of immunity, dyspepsia, diarrhea and constipation | |
| KR102552609B1 (en) | Composition for improving memory and learning ability and relieving stress | |
| KR20200047939A (en) | Anti-diabetic and Anti-obese Fermented Composition Comprising Fermented Hot Pepper and Fermented Hot Pepper Paste |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190425 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200225 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20200221 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200423 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200625 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20201110 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20210104 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210212 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20210601 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210604 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6898628 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |