JP5751849B2 - Dysphagia improving agent - Google Patents

Dysphagia improving agent Download PDF

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JP5751849B2
JP5751849B2 JP2011018030A JP2011018030A JP5751849B2 JP 5751849 B2 JP5751849 B2 JP 5751849B2 JP 2011018030 A JP2011018030 A JP 2011018030A JP 2011018030 A JP2011018030 A JP 2011018030A JP 5751849 B2 JP5751849 B2 JP 5751849B2
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JP2012158537A (en
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康英 日比野
康英 日比野
飯塚 博
博 飯塚
真理 岡崎
真理 岡崎
広和 松崎
広和 松崎
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野田食菌工業株式会社
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本発明は、高齢者や脳卒中既往者など、飲食物を噛み下したり飲み込んだりすることに支障のある者の障害を改善するための嚥下障害改善剤に関する。   The present invention relates to a dysphagia improving agent for improving a disorder of a person who has difficulty in biting or swallowing food or drink such as an elderly person or a person who has a history of stroke.

高齢者などは、飲食物を噛み下したり飲み込んだりする際にむせたり誤嚥を起すことがあり、これにより、往々にして、日常の食事の快適性が損なわれるという問題があった。そして老化の進行や病気などに起因して障害が進行すると、通常のように口から食事をするのが困難な症状となり、窒息を起こす危険もあった。また、脳卒中既往者においては、嚥下障害が30〜50%と高率で認められ、嚥下性の肺炎がリスクファクターとなって、脳卒中による合併症の中でも肺炎が死亡率の高いものの1つであった。従来、これら嚥下障害を改善するための改善剤への要望は高い。   The elderly and the like sometimes suffer from aspiration or aspiration when biting or swallowing food and drink, and this often causes a problem that the comfort of daily meals is impaired. When the disorder progressed due to the progress of aging or illness, it became difficult to eat from the mouth as usual, and there was a risk of suffocation. In patients with a history of stroke, dysphagia was observed at a high rate of 30 to 50%, swallowing pneumonia was a risk factor, and pneumonia was one of the most common complications due to stroke. It was. Conventionally, there is a high demand for an improving agent for improving these dysphagia.

一方、キノコ類の抽出物等を、嚥下に支障のある者に適した飲食品等に配合することが行われている。例えば、特許文献1には、茶を主な成分とする飲料に関し、とくに飲料の嚥下に支障のある高齢者にとって容易に飲用することができるようなゼリー状の飲料に関する発明が開示され、茶粉、茶抽出液、マッシュルーム抽出物及びゲル化剤が水に混合されているゼリー飲料を提供することが記載されている。(特許文献1の請求項3参照)。また、特許文献2には、咀嚼や嚥下等の生理機能が低下した高齢者でも容易に食することができ、さらにきのこ独特の風味をそのまま残した、リオフィラム属きのこ由来の食品素材を提供することを目的とする発明が開示され、脱脂処理することなく抽出されたリオフィラム属きのこ子実体由来の熱水抽出物であって、4℃で24時間放置した際に破断応力が1×10Pa以上のゲルを形成する熱水抽出物又はその乾燥物を提供することが記載されている。(特許文献2の請求項1参照)。また、特許文献3には、油脂含有量が製品に対して5%以下であり、魚介類エキス及び/又はきのこ類エキスを含有し、粘度が1〜30Pa・sであることを特徴とする咀嚼・嚥下機能低下者用酸性調味料の発明が開示されている(特許文献3の請求項1参照)。 On the other hand, mushroom extracts and the like are blended into foods and drinks suitable for those who have difficulty in swallowing. For example, Patent Document 1 discloses an invention relating to a beverage containing tea as a main ingredient, and in particular, an invention relating to a jelly-like beverage that can be easily consumed by elderly people who have trouble swallowing the beverage. It provides a jelly beverage in which a tea extract, a mushroom extract and a gelling agent are mixed in water. (See claim 3 of Patent Document 1). Patent Document 2 provides a food material derived from a lyophilum genus that can be eaten easily even by elderly people who have decreased physiological functions such as chewing and swallowing, and that still retains the unique flavor of mushrooms. Is a hot water extract derived from a lyophilum genus mushroom fruit body that has been extracted without degreasing and has a breaking stress of 1 × 10 3 Pa or more when left at 4 ° C. for 24 hours It is described to provide a hot water extract or a dried product thereof that forms a gel of (See claim 1 of Patent Document 2). Patent Document 3 discloses a mastication characterized in that the fat content is 5% or less based on the product, contains a seafood extract and / or a mushroom extract, and has a viscosity of 1 to 30 Pa · s. -The invention of the acidic seasoning for persons with reduced swallowing function is disclosed (see claim 1 of Patent Document 3).

特開2001−299297号公報JP 2001-299297 A 特開2004−215663号公報JP 2004-215663 A 特開2006−174830号公報JP 2006-174830 A

しかしながら、キノコ類の抽出物等を、嚥下に支障のある者に適した飲食品等に配合するだけでは、必ずしも嚥下障害を改善する効果が十分とはいえなかった。   However, the effect of improving dysphagia has not always been sufficient only by adding an extract of mushrooms or the like to a food or drink suitable for those who have difficulty in swallowing.

したがって、本発明は、キノコ類等の担子菌由来成分を有効成分とし、副作用なく安全に服用できる嚥下障害改善剤であって、嚥下障害を改善する効果の高いものを提供することにある。   Accordingly, the present invention is to provide a dysphagia improving agent that has a basidiomycete-derived component such as mushrooms as an active ingredient and can be safely taken without side effects, and has a high effect of improving dysphagia.

上記目的を達成するため、本発明は、植物繊維質原料を含む培地を用いて担子菌の菌糸体を培養し、その培養物から抽出して得た、糖質、蛋白質、及び水溶性リグニンを含む抽出物を有効成分として含有することを特徴とする嚥下障害改善剤を提供するものである。   In order to achieve the above object, the present invention cultivates mycelia of basidiomycetes using a medium containing plant fiber raw materials, and extracts carbohydrates, proteins, and water-soluble lignin obtained by extraction from the culture. The present invention provides an agent for improving dysphagia characterized by containing an extract containing it as an active ingredient.

本発明の嚥下障害改善剤においては、前記抽出物は、前記培養物から、担子菌の自己消化を行って得られたものであることが好ましい。   In the dysphagia improving agent of the present invention, the extract is preferably obtained by autolysis of basidiomycetes from the culture.

また、前記植物繊維質原料が、禾本科植物から調製されたものであることが好ましく、バガス、トウモロコシの茎葉、小麦ふすま、米糠、稲藁、茅、熊笹、及び竹から選ばれた1種又は2種以上から調製されたものであることがより好ましい。   In addition, the plant fiber raw material is preferably prepared from a plant family plant, one selected from bagasse, corn stover, wheat bran, rice bran, rice bran, rice bran, bear cocoon, and bamboo or More preferably, it is prepared from two or more.

更に、前記担子菌が、マンネン茸、ブクリョウ、コフキサルノコシカケ、カワラ茸、椎茸、ヒラ茸、マイ茸、エノキ茸、シメジ茸、ヤマブシ茸、及びアガリクスから選ばれたものであることが好ましい。   Furthermore, it is preferable that the basidiomycete is selected from mannenpox, bukkyou, kofukisarokoshikake, kawara mushroom, shiitake mushroom, hira mushroom, mai mushroom, enoki mushroom, shimeji mushroom, yamabushi mushroom, and agaricus.

植物繊維質原料を含む培地を用いて担子菌の菌糸体を培養すると、培地中に含まれるセルロース、ヘミセルロース、リグニンなどが、培養期間中に担子菌の菌糸体が生産するセルラーゼ、フェノールオキシダーゼ、ラッカーゼ、パーオキシダーゼ、プロテアーゼなどの酵素により、消化、分解、及び縮合を起こしてペントース主体のプロテオグリカンを生成する。また、水溶性化した変性水溶性リグニンが生成する。本発明によれば、このように培養培地からの成分を複合的に含む抽出物を有効成分とすることにより、優れた嚥下障害改善剤を提供することができる。また、その有効成分は天然物から得られた抽出物であり、日常的に、副作用なく安全に服用することができる。   When a mycelium of basidiomycetes is cultured using a medium containing plant fiber raw materials, cellulose, hemicellulose, lignin, etc. contained in the medium are cellulase, phenol oxidase, and laccase produced by mycelia of basidiomycetes during the culture period. Pentose-based proteoglycans are produced by digestion, degradation, and condensation with enzymes such as peroxidase and protease. Moreover, the water-soluble modified water-soluble lignin is generated. According to the present invention, an excellent dysphagia-improving agent can be provided by using, as an active ingredient, an extract containing the components from the culture medium in a complex manner. Moreover, the active ingredient is an extract obtained from a natural product, and can be safely taken on a daily basis without side effects.

試験例1の結果を示す図表である。6 is a chart showing the results of Test Example 1. 試験例2の結果を示す図表である。10 is a chart showing the results of Test Example 2. 試験例3において測定した筋電図の例を示す図表である。10 is a chart showing an example of an electromyogram measured in Test Example 3. 試験例3の結果を示す図表である。10 is a chart showing the results of Test Example 3. 試験例4の結果を示す顕微鏡写真である。6 is a photomicrograph showing the results of Test Example 4.

本発明に用いられる担子菌としては、特に限定されず、例えば、マンネン茸、ブクリョウ、コフキサルノコシカケ、カワラ茸などの薬用茸や、椎茸、ヒラ茸、マイ茸、エノキ茸、シメジ茸、ヤマブシ茸、アガリクスなどの食用茸など各種のものが挙げられる。この中でも、特にマンネン茸、椎茸が好ましく採用される。   The basidiomycetes used in the present invention are not particularly limited, for example, medicinal mushrooms such as mannen mushrooms, bukkyou, kofukisarokoshikake, kawara mushrooms, shiitake mushrooms, Japanese cypress mushrooms, mai mushrooms, enoki mushrooms, shimeji mushrooms, yamabushi mushrooms, Various foods such as edible rice cakes such as Agaricus are listed. Among these, mannen mushrooms and shiitake mushrooms are particularly preferably employed.

本発明では、これらの担子菌の菌糸体を、植物繊維質原料を含む培地を用いて培養し、その培養物から有効成分を抽出する。この場合、培地としては、固体培地、液体培地の何れも使用できる。培地に用いる植物繊維質原料としては、リグニンを含有する植物から調製されたものが好ましく用いられる。リグニンを含有する植物としては、禾本科植物、例えばバガス(さとうきびの搾り粕)、トウモロコシの茎葉、小麦ふすま、米糠、稲藁、茅などが好ましく用いられる。この他に、熊笹、竹なども使用できる。特に好ましくは、バガス、熊笹の茎葉、とうもろこしの茎から選ばれた少なくとも1種と、米糠とを含む培地が用いられる。また、培地には、必要に応じて他の栄養成分として、酵母エキス、乾燥酵母、クロレラ、スピルリナ、コーンミール、おからなどを添加混合してもよい。   In the present invention, mycelia of these basidiomycetes are cultured using a medium containing plant fiber raw material, and active ingredients are extracted from the culture. In this case, either a solid medium or a liquid medium can be used as the medium. As the plant fiber raw material used for the medium, those prepared from plants containing lignin are preferably used. As the lignin-containing plant, a plant family such as bagasse (squeezed sugar cane), corn stover, wheat bran, rice bran, rice straw, and straw are preferably used. In addition, bears, bamboo, etc. can be used. Particularly preferably, a culture medium containing at least one selected from bagasse, bear stems and corn stalks and rice bran is used. In addition, yeast extract, dry yeast, chlorella, spirulina, corn meal, okara, and the like may be added and mixed with the medium as other nutritional components as necessary.

担子菌の菌糸体の培養は、上記のような植物繊維質原料を含む培地に、前記担子菌の菌糸を接種して行う。固体培地の場合は、水分が60〜80%となるように調製し、常法に従い高圧蒸気滅菌した後、菌糸を接種し、例えば温度が18〜25℃に空調された培養室で3〜6か月培養する。こうして菌糸体が蔓延した培地は、温度処理室に移して変温処理を行うことが好ましい。変温処理は、例えば最初に30〜34℃で24〜48時間加温し、次に低温室に移して3〜5日間処理する。その後培養室に移すと子実体の発生が始まるが、この時点で培養を終了し、培養物を破砕機で破砕する。   The mycelium of basidiomycetes is cultured by inoculating the mycelium of basidiomycetes in a medium containing the above-mentioned plant fiber raw material. In the case of a solid medium, the water content is adjusted to 60 to 80%, sterilized by autoclaving according to a conventional method, inoculated with mycelia, and, for example, 3 to 6 in a culture room conditioned at a temperature of 18 to 25 ° C. Incubate for months. The medium in which the mycelium has spread is preferably transferred to a temperature treatment chamber and subjected to a temperature change treatment. In the temperature change treatment, for example, the mixture is first heated at 30 to 34 ° C. for 24 to 48 hours, and then transferred to a low temperature chamber and treated for 3 to 5 days. After that, when it is transferred to a culture chamber, the generation of fruiting bodies starts.

一方、液体培地の場合は、上記のような植物原料を細かく破砕し、必要に応じて米糠等の他の栄養成分を加え、原料が5〜20質量%となるように培地を調製した後、通気攪拌培養もしくは振盪培養により、好ましくは20〜28℃の温度で1週間〜2か月間程度培養を行う。培養は培地のpHが3.5〜5に低下し、培地中に菌糸が蔓延した状態で終了する。   On the other hand, in the case of a liquid medium, after pulverizing the plant raw material as described above, adding other nutritional components such as rice bran as necessary, and preparing the medium so that the raw material is 5 to 20% by mass, The culture is preferably carried out by aeration and agitation culture or shaking culture at a temperature of 20 to 28 ° C. for about 1 week to 2 months. The culture is terminated when the pH of the medium is lowered to 3.5 to 5 and the mycelium is prevalent in the medium.

培養終了後培養物を抽出する。その好ましい方法としては、菌糸体に内在する酵素を利用して菌糸体を自己消化させると共に培養物を抽出するようにすることが好ましい。   After completion of the culture, the culture is extracted. As a preferable method, it is preferable to self-digest the mycelium and extract the culture using an enzyme present in the mycelium.

具体的には、固体培地の場合は培養が終了した培養物を破砕し、必要に応じて少量の水を加え、30〜60℃で3〜6時間処理し、菌糸体の酵素反応を進め、自己消化させる。次いで、この破砕物を50℃以上の温水又は熱水に浸潤させ、有効成分を抽出する。抽出は、例えば1.2kg/cmの蒸気圧下で120℃というような加圧高温下で行うこともできる。こうして得られた抽出懸濁液を、好ましくは濾過または遠心分離して濾液又は上清を採取することにより、培地の分解物、菌糸体の代謝産物及び菌糸体細胞の分解物などを含む抽出物を得ることができる。 Specifically, in the case of a solid medium, the culture after culturing is crushed, a small amount of water is added as necessary, and the mixture is treated at 30 to 60 ° C. for 3 to 6 hours to advance the mycelial enzyme reaction, Let yourself digest. Subsequently, this crushed material is infiltrated with warm water or hot water of 50 ° C. or higher, and an active ingredient is extracted. The extraction can also be carried out under a high pressure such as 120 ° C. under a vapor pressure of 1.2 kg / cm 2 , for example. The extract suspension thus obtained is preferably filtered or centrifuged, and the filtrate or supernatant is collected to obtain an extract containing a degradation product of the culture medium, a mycelium metabolite, a mycelium cell degradation product, and the like. Can be obtained.

一方、液体培養の場合は、培養物全体を30〜60℃で3〜6時間処理し、菌糸体を自己消化させ、液体の懸濁培養物を得る。次いで、必要に応じて少量の水を加え、50℃以上、場合によっては高圧条件下(例えば1.2kg/cmの蒸気圧下)に加熱し、抽出物を採取する。この抽出物を、必要に応じて濾過又は遠心分離して濾液又は上清を採取することにより、培地の分解物、菌糸体の代謝産物及び菌糸体細胞の分解物などを含む抽出物を得ることができる。 On the other hand, in the case of liquid culture, the whole culture is treated at 30 to 60 ° C. for 3 to 6 hours to self-digest the mycelium to obtain a liquid suspension culture. Then, if necessary, a small amount of water is added, and the mixture is heated to 50 ° C. or higher, possibly under high pressure (for example, under a vapor pressure of 1.2 kg / cm 2 ), and the extract is collected. By filtering or centrifuging the extract as necessary, and collecting the filtrate or supernatant, an extract containing a degradation product of a medium, a mycelium metabolite, a mycelium cell degradation product, or the like is obtained. Can do.

こうして得られた抽出物は、液状のものをそのまま又は濃縮して利用することもできるが、凍結乾燥や噴霧乾燥などの手段によって粉末化して利用することもできる。抽出物として液状のものをそのまま又は濃縮して利用する場合には、例えば液状又はゼリー状のドリンクタイプの製品とすることもできる。抽出物を粉末化して利用する場合には、常法によって、粉末、顆粒、錠剤、カプセル剤等として製品化することができる。 The extract thus obtained can be used as it is or after being concentrated, but can also be used by pulverizing it by means such as freeze drying or spray drying. When using those liquid as such or concentrated to as extract, Ru can also be, for example, a liquid or jelly drink type products. When utilizing the extract was triturated a conventional method by, powders, granules, tablets, Ru can be manufactured as capsules and the like.

本発明の有効成分である上記抽出物(植物繊維質原料を含む培地に担子菌の菌糸体を培養して得られた培養物から抽出された成分)は、糖質を主体とした物質であるが、次のような物理化学的性質を有していることが好ましい。   The above extract, which is an active ingredient of the present invention (a component extracted from a culture obtained by culturing mycelia of basidiomycetes in a medium containing plant fiber raw material) is a substance mainly composed of carbohydrates. However, it is preferable to have the following physicochemical properties.

(1) 分子量:100万以下
(2) 化学組成:
・糖質:30〜50質量%
・蛋白質:8〜20質量%
・水溶性リグニン:20〜40質量%
(1) Molecular weight: 1 million or less (2) Chemical composition:
・ Sugar: 30-50% by mass
・ Protein: 8-20% by mass
Water-soluble lignin: 20-40% by mass

なお、上記抽出物中の糖質、蛋白質、及び水溶性リグニンの組成の範囲を特定するためには、それぞれフェノール硫酸法、セミミクロケルダール法、アセチルブロマイド法で測定して求められる質量組成で特定することが好ましい。   In addition, in order to specify the range of the composition of the saccharide, protein, and water-soluble lignin in the above extract, it is specified by the mass composition obtained by measurement by the phenol sulfate method, the semi-micro Kjeldahl method, and the acetyl bromide method, respectively It is preferable.

マンネン茸を用いて得られた上記培養抽出物(粉末)について安全性を試験した結果は次の通りである。   The results of testing the safety of the above culture extract (powder) obtained using mannen koji are as follows.

(A) 急性毒性試験(最小致死量)
・ラット単回経口投与 雄:22,500mg/Kg 以上
雌:22,500mg/Kg 以上
・マウス単回経口投与 雄:2,000mg/Kg 以上
雌:2,000mg/Kg 以上
(B) ラット3か月反復経口投与試験(最大無作用量)
雄:3,610mg/Kg
雌:4,190mg/Kg
(A) Acute toxicity test (minimum lethal dose)
・ Rat single oral administration Male: 22,500mg / Kg or more
Female: 22,500 mg / Kg or more ・ Single mouse oral administration Male: 2,000 mg / Kg or more
Female: 2,000 mg / Kg or more (B) Rat 3-month repeated oral administration test (maximum no-effect level)
Male: 3,610 mg / Kg
Female: 4,190mg / Kg

本発明の嚥下障害改善剤の有効投与量は、上記抽出物の固形分換算で、経口摂取において成人1日当たり1〜10gである。投与量がこれよりも少ないと、嚥下障害を改善する効果が十分に得られず、投与量がこれよりも多いと、軟便又は腹部膨満感が生じることがある。ただし、投与量が上記より多くても安全性には問題がない。   The effective dose of the agent for improving dysphagia of the present invention is 1 to 10 g per day for an adult in terms of solid intake in terms of solid content. If the dosage is smaller than this, the effect of improving dysphagia cannot be obtained sufficiently, and if the dosage is larger than this, loose stool or abdominal bloating may occur. However, there is no problem in safety even if the dose is larger than the above.

以下実施例を挙げて本発明を具体的に説明するが、これらの実施例は本発明の範囲を限定するものではない。   EXAMPLES Hereinafter, the present invention will be specifically described with reference to examples, but these examples do not limit the scope of the present invention.

(1)培養培地抽出物の調製例
<調製例1>(バガスを用いたマンネン茸菌の固体培養)
バガス90質量部と、脱脂米糠10質量部とを配合し、水分70%となるように調整して固形培地を作り、常法通り高圧蒸気滅菌した。この固体培地にマンネン茸の菌糸を接種し、25℃に温度調節した培養室内で3か月培養し、培地中に菌糸体が蔓延した後、温度処理室に移して35℃で24時間加温し、次いで10℃の低温室で3日間処理した。その後、上記培養室で3日間培養し、培地を破砕機で親指程度の大きさに破砕した。破砕した培地を40℃で6時間処理し、自己消化を促進させた後、抽出タンクに詰め、60℃の温水を循環させながら16時間抽出した。得られた抽出液をカートリッジフィルターで濾過し、更にメンブランフィルターで濾過除菌後、濃縮し、凍結乾燥により褐色の粉末を得た。その成分を分析した結果は以下の通りであった。
(1) Preparation Example of Culture Medium Extract <Preparation Example 1> (Solid culture of N. gonorrhoeae using bagasse)
90 parts by mass of bagasse and 10 parts by mass of defatted rice bran were mixed, adjusted to a moisture content of 70%, a solid medium was prepared, and autoclaved as usual. This solid medium is inoculated with mycelium of mannen moth and cultured in a culture chamber adjusted to 25 ° C. for 3 months. After the mycelium spreads in the medium, it is transferred to a temperature treatment chamber and heated at 35 ° C. for 24 hours. Then, it was treated in a low temperature room at 10 ° C. for 3 days. Then, it culture | cultivated for 3 days in the said culture room, and crushed the culture medium in the magnitude | size about the thumb with the crusher. The crushed medium was treated at 40 ° C. for 6 hours to promote autolysis, then packed in an extraction tank, and extracted for 16 hours while circulating 60 ° C. warm water. The obtained extract was filtered through a cartridge filter, further sterilized by filtration through a membrane filter, concentrated, and freeze-dried to obtain a brown powder. The results of analyzing the components were as follows.

・糖質 :40質量%(フェノール硫酸法)
・蛋白質 :12質量%(セミミクロケルダール法)
・水溶性リグニン :30質量%(アセチルブロマイド法)
・無機質 :13質量%(直接灰化法)
・ Sugar: 40% by mass (phenol sulfate method)
・ Protein: 12% by mass (semi-micro Kjeldahl method)
・ Water-soluble lignin: 30% by mass (acetyl bromide method)
・ Inorganic: 13% by mass (direct ashing method)

(2)動物試験
上記調製例1の方法で得たマンネン茸の菌糸体培養培地抽出物(以下、「MAK」という。)について、ラット(Sprague-Dawley、三協ラボサービス)を利用した動物試験により、その嚥下障害の改善の効果を検討した。
(2) Animal test The animal test using the rat (Sprague-Dawley, Sankyo Lab Service) for the mycelium culture medium extract (hereinafter referred to as "MAK") of mannen koji obtained by the method of Preparation Example 1 above. Thus, the effect of improving the dysphagia was examined.

まず、ラットをハロタン麻酔し、その頸部を正中切開し両側の総頚動脈を迷走神経より剥離し、これを結紮する手術を施すことにより、嚥下能力の低下したラットを作出した。一方、頸部切開および両側総頚動脈の剥離のみの手術を施したラットを、偽手術群とした。その手術の2週間後又は4週間後に、Kajii らの方法(Kajii et al., (2002) Physiology & Behavior 77 321- 325)を参考に、嚥下測定のための処置を施した。具体的には、ウレタン麻酔下、口腔内にポリエチレン製ガイドカニューレを挿入、固定し、そのガイドカニューレを介してポリエチレン製カニューレを咽頭に留置した。これにより、そのカニューレを通じて咽喉頭部に刺激用の試験液を直接注入することができるようにした。また、顎舌骨筋に筋電図用の電極を刺入し、嚥下に伴う筋収縮を記録できるようにした。   First, rats were anesthetized with halothane, a midline incision was made in the neck, the common carotid arteries on both sides were detached from the vagus nerve, and ligation was performed to create rats with reduced swallowing ability. On the other hand, rats subjected to surgery only for neck incision and exfoliation of both common carotid arteries were set as a sham operation group. Two or four weeks after the operation, treatment for swallowing was performed with reference to the method of Kajii et al. (Kajii et al., (2002) Physiology & Behavior 77 321-325). Specifically, a polyethylene guide cannula was inserted and fixed in the oral cavity under urethane anesthesia, and the polyethylene cannula was placed in the pharynx through the guide cannula. As a result, the stimulation test solution can be directly injected into the throat through the cannula. In addition, an electromyographic electrode was inserted into the hyoid hyoid muscle to record the muscle contraction associated with swallowing.

MAKを投与する場合には、嚥下能力を低下させるための手術の終了後から嚥下測定まで2週間、1g/kgの投与量3mL/kgの容量で、ラットに1日1回経口ゾンデにて投与した。また、対照として蒸留水を、同様に手術終了後から嚥下測定までの2週間投与した。   When MAK is administered, rats are administered once daily with an oral sonde at a dose of 3 mL / kg at a dose of 3 g / kg for 2 weeks from the end of surgery to reduce swallowing ability until measurement of swallowing. did. Moreover, distilled water was similarly administered as a control for 2 weeks from the end of the surgery until swallowing measurement.

以下、試験例1では基礎検討として各種の試験液で刺激したとき嚥下回数を測定し、試験例2では目視により測定した嚥下回数と筋電図を用いた嚥下に伴う筋収縮回数との相関について検討し、試験例3においてMAK投与の効果を調べた。   Hereinafter, in Test Example 1, the number of swallows was measured as a basic study when stimulated with various test solutions, and in Test Example 2, the correlation between the number of swallows measured visually and the number of muscle contractions associated with swallowing using an electromyogram The effect of MAK administration was examined in Test Example 3.

<試験例1>
基礎検討として蒸留水、クエン酸(1、3、又は10mM)、又はカプサイシン(100nM)の溶液を注入して咽喉頭を刺激したとき嚥下回数を、目視により測定した。すなわち、刺激用ポリエチレン製カニューレをマイクロシリンジポンプ(KD SCIENTIFIC社)につなげて流速を調整し、3.3μL/秒の流速で各試験液50μLを注入し、それを3回繰り返して、その間の嚥下回数を目視により観察した。試験では、同じラットに対し、試験液を、蒸留水、1mMクエン酸、3mMクエン酸、10mMクエン酸、100nMカプサイシンの順番で繰り返し注入して、それぞれの試験液による刺激に対する嚥下回数を測定した。
<Test Example 1>
As a basic study, the number of swallowing was visually measured when a solution of distilled water, citric acid (1, 3, or 10 mM) or capsaicin (100 nM) was injected to stimulate the pharynx. In other words, a polyethylene cannula for stimulation was connected to a micro syringe pump (KD SCIENTIFIC) to adjust the flow rate, and 50 μL of each test solution was injected at a flow rate of 3.3 μL / sec. The number of times was observed visually. In the test, the test solution was repeatedly injected into the same rat in the order of distilled water, 1 mM citric acid, 3 mM citric acid, 10 mM citric acid, and 100 nM capsaicin, and the number of swallows in response to stimulation with each test solution was measured.

その結果、図1に示すように、総頚動脈を結紮しない偽手術群(図中、「1」又は「2」で示す。)においては、その手術後2週間と4週間において、蒸留水、1mMクエン酸、3mMクエン酸、10mMクエン酸、100nMカプサイシンの順で、刺激による嚥下回数が増加した。一方、両側総頚動脈に結紮を施した手術群(図中、「3」又は「4」で示す。)においても、同様に、水、1mMクエン酸、3mMクエン酸、10mMクエン酸、100nMカプサイシンの順で、刺激による嚥下回数が増加したが、各試験液における嚥下回数は、偽手術群に比べて顕著に低下していた。なお、手術後4週間の10mMクエン酸と100nMカプサイシンの嚥下回数は、手術後2週間に比べて増加していた。これは、自然治癒的に嚥下の能力が一部回復したためであると考えられた。   As a result, as shown in FIG. 1, in the sham operation group (indicated by “1” or “2” in the figure) in which the common carotid artery is not ligated, distilled water, 1 mM was obtained at 2 weeks and 4 weeks after the operation. The number of swallows by stimulation increased in the order of citric acid, 3 mM citric acid, 10 mM citric acid, and 100 nM capsaicin. On the other hand, in the surgical group (indicated by “3” or “4” in the figure) in which the bilateral common carotid artery was ligated, water, 1 mM citric acid, 3 mM citric acid, 10 mM citric acid, and 100 nM capsaicin were similarly produced. In order, the number of swallows by stimulation increased, but the number of swallows in each test solution decreased significantly compared to the sham operation group. It should be noted that the number of swallows of 10 mM citric acid and 100 nM capsaicin 4 weeks after surgery was increased compared to 2 weeks after surgery. This was thought to be due to a partial recovery of swallowing ability spontaneously.

<試験例2>
目視により測定した嚥下回数と筋電図を用いた嚥下に伴う筋収縮回数との相関について検討した。そのために、手術後2週間のラットに対して、試験例1と同様にして、蒸留水、クエン酸(1、3、又は10mM)、又はカプサイシン(100nM)の溶液を注入して咽喉頭を刺激し、各試験液において、目視により測定した嚥下回数と、筋電図に基づく筋収縮回数との測定結果を比較した。
<Test Example 2>
We investigated the correlation between the number of swallows measured visually and the number of muscle contractions associated with swallowing using electromyography. To this end, rats that were 2 weeks after surgery were injected with distilled water, citric acid (1, 3, or 10 mM) or capsaicin (100 nM) in the same manner as in Test Example 1 to stimulate the pharynx. In each test solution, the measurement results of the number of swallows measured visually and the number of muscle contractions based on the electromyogram were compared.

その結果、図2に示すように、目視により測定した嚥下回数(図中、「1」又は「3」で示す。)と、筋電図に基づく筋収縮回数(図中、「2」又は「4」で示す。)とは、ほぼ良好に相関していた。   As a result, as shown in FIG. 2, the number of swallows measured visually (indicated by “1” or “3” in the figure) and the number of muscle contractions based on the electromyogram (in the figure, “2” or “ 4 ”)).

<試験例3>
MAK投与の効果を調べた。そのために、総頚動脈を結紮しない偽手術を施してその後2週間蒸留水を投与したラットと、両側総頚動脈に結紮を施してその手術後2週間蒸留水を投与したラットと、両側総頚動脈に結紮を施してその手術後2週間MAKを投与したラットに対して、試験例1と同様にして、蒸留水、クエン酸(1、3、又は10mM)、又はカプサイシン(100nM)の溶液を注入して咽喉頭を刺激し、各試験液における嚥下回数を測定した。
<Test Example 3>
The effect of MAK administration was examined. For this purpose, a sham operation without ligating the common carotid artery and rats administered with distilled water for 2 weeks, a rat ligated to the bilateral common carotid artery and administered with distilled water for 2 weeks after the surgery, and ligated to the bilateral common carotid artery In the same manner as in Test Example 1, a solution of distilled water, citric acid (1, 3, or 10 mM), or capsaicin (100 nM) was injected into rats administered MAK for 2 weeks after the surgery. The larynx was stimulated and the number of swallows in each test solution was measured.

図3には、総頚動脈を結紮しない偽手術を施してその後2週間蒸留水を投与したラット(図中、「1」で示す。)と、両側総頚動脈に結紮を施してその手術後2週間蒸留水を投与したラット(図中、「2」で示す。)と、両側総頚動脈に結紮を施してその手術後2週間MAKを投与したラット(図中、「3」で示す。)について、蒸留水(図中、「a」で示す。)、3mMクエン酸(図中、「b」で示す。)、又は100nMカプサイシン(図中、「c」で示す。)の溶液を注入して咽喉頭を刺激したときのそれぞれの筋電図の一例を示す。すなわち合計9例の筋電図を示す。また図中上段には、各試験液による刺激での筋収縮のシグナルについて、その強度(縦軸)と時間(横軸)のスケールを拡大した筋電図を示す。   FIG. 3 shows a rat (indicated by “1” in the figure) that had undergone a sham operation without ligating the common carotid artery and then administered distilled water for 2 weeks, and ligated to the bilateral common carotid artery for 2 weeks after the operation. For rats administered with distilled water (indicated by “2” in the figure) and rats ligated to the bilateral common carotid artery and administered MAK for 2 weeks after the surgery (indicated by “3” in the figure). A solution of distilled water (indicated by “a” in the figure), 3 mM citric acid (indicated by “b” in the figure), or 100 nM capsaicin (indicated by “c” in the figure) was injected into the throat. An example of each electromyogram when a head is stimulated is shown. That is, a total of 9 electromyograms are shown. Moreover, the electromyogram which expanded the scale of the intensity | strength (vertical axis) and time (horizontal axis) about the signal of the muscle contraction by the stimulus by each test solution is shown in the upper part of the figure.

図3に示されるように、総頚動脈を結紮しない偽手術を施したラットであって蒸留水を投与したもの(図中、「1」で示す。)においては、試験液として蒸留水、3mMクエン酸、100nMカプサイシンの順で、これらの刺激による筋収縮回数が増加した。一方、両側総頚動脈に結紮を施したラットであって蒸留水を投与したもの(図中、「2」で示す。)においては筋収縮回数が減り、100nMカプサイシンでの刺激による筋収縮回数の減少が特に顕著であった。これに対して、両側総頚動脈に結紮を施したラットであってMAKを投与したもの(図中、「3」で示す。)においては、偽手術群であって蒸留水を投与したラット(図中、「1」で示す。)の場合と同程度にまで、筋収縮回数が回復した。   As shown in FIG. 3, in rats subjected to sham surgery without ligating the common carotid artery and administered with distilled water (indicated by “1” in the figure), distilled water, 3 mM citric acid as a test solution. In the order of acid and 100 nM capsaicin, the number of muscle contractions by these stimuli increased. On the other hand, in rats with ligated bilateral common carotid arteries administered with distilled water (indicated by “2” in the figure), the number of muscle contractions is reduced, and the number of muscle contractions is reduced by stimulation with 100 nM capsaicin. Was particularly prominent. In contrast, in the rat ligated to the bilateral common carotid arteries and administered with MAK (indicated by “3” in the figure), the rats in the sham operation group and administered with distilled water (see FIG. The number of muscle contractions recovered to the same level as in the case of “1”.

図4には全ての結果をまとめたグラフを示す。なお結果は、目視により測定した嚥下回数又は筋電図に基づく筋収縮回数の総計で示した。   FIG. 4 shows a graph summarizing all the results. The results are shown as the total number of swallows or muscle contractions based on electromyogram measured visually.

図4に示されるように、総頚動脈を結紮しない偽手術を施したラットであって蒸留水を投与したもの(図中、「1」で示す。)においては、試験液として蒸留水、1mMクエン酸、3mMクエン酸、10mMクエン酸、100nMカプサイシンの順で、これらの刺激による嚥下又は筋収縮の回数が増加した。一方、両側総頚動脈に結紮を施したラットであって蒸留水を投与したもの(図中、「2」で示す。)においては嚥下又は筋収縮の回数が顕著に減少した。これに対して、両側総頚動脈に結紮を施したラットであってMAKを投与したもの(図中、「3」で示す。)においては、偽手術群であって蒸留水を投与したラット(図中、「1」で示す。)の場合と同程度にまで、各試験液での刺激による嚥下又は筋収縮の回数が回復した。   As shown in FIG. 4, in a rat subjected to a sham operation without ligating the common carotid artery and administered with distilled water (indicated by “1” in the figure), distilled water, 1 mM citric acid was used as a test solution. In the order of acid, 3 mM citric acid, 10 mM citric acid, and 100 nM capsaicin, the number of swallowing or muscle contraction by these stimuli increased. On the other hand, the number of swallowing or muscle contraction was significantly reduced in rats ligated to the bilateral common carotid artery and administered with distilled water (indicated by “2” in the figure). In contrast, in the rat ligated to the bilateral common carotid arteries and administered with MAK (indicated by “3” in the figure), the rats in the sham operation group and administered with distilled water (see FIG. The frequency of swallowing or muscle contraction by stimulation with each test solution was recovered to the same extent as in the case of “1”.

以上から、MAKの投与によって、嚥下障害が改善されることが明らかとなった。   From the above, it has become clear that administration of MAK improves dysphagia.

<試験例4>
総頚動脈結紮による嚥下障害にはチロシンヒドロキシラーゼ(ドパミン神経系)が関与しているとの報告がある。そこで本試験では、総頚動脈を結紮しない偽手術を施してその後2週間蒸留水を投与したラット(図中、「1」で示す。)と、両側総頚動脈に結紮を施してその手術後2週間蒸留水を投与したラット(図中、「2」で示す。)と、両側総頚動脈に結紮を施してその手術後2週間MAKを投与したラット(図中、「3」で示す。)について、線条体を含む脳冠状切片を作成し、免疫組織染色法により、チロシンヒドロキシラーゼの発現の状態を調べた。具体的には、正常ヤギ血清でブロッキングを行った後抗チロシンヒドロキシラーゼ抗体 (1:1,000希釈, Chemicon社製) と反応させ、アビジン・ビオチンペルオキシダーゼ法にて二次抗体反応を行い、ジアミノベンチジンにて発色させ、顕微鏡観察した。図5にその顕微鏡写真を示す。
<Test Example 4>
It has been reported that tyrosine hydroxylase (dopamine nervous system) is involved in dysphagia caused by ligation of the common carotid artery. Therefore, in this study, a sham operation without ligating the common carotid artery was performed, and then distilled water was administered for 2 weeks (indicated by “1” in the figure), and ligation was performed on the bilateral common carotid artery for 2 weeks after the operation. For rats administered with distilled water (indicated by “2” in the figure) and rats ligated to the bilateral common carotid artery and administered MAK for 2 weeks after the surgery (indicated by “3” in the figure). A coronal section containing the striatum was prepared, and the expression state of tyrosine hydroxylase was examined by immunohistochemical staining. Specifically, after blocking with normal goat serum, it was reacted with an anti-tyrosine hydroxylase antibody (1: 1,000 dilution, manufactured by Chemicon), followed by a secondary antibody reaction by avidin-biotin peroxidase method, and diaminobenzidine. The color was developed with a microscope and observed under a microscope. The micrograph is shown in FIG.

その結果、両側総頚動脈に結紮を施してその手術後2週間蒸留水を投与したラット(図中、「2」で示す。)では、総頚動脈を結紮しない偽手術を施してその後2週間蒸留水を投与したラット(図中、「1」で示す。)に比べ、線条体でのチロシンヒドロキシラーゼの発現量が減少していた。一方、両側総頚動脈に結紮を施してその手術後2週間MAKを投与したラット(図中、「3」で示す。)では、その発現量が偽手術ラットと同程度まで回復していた。したがって、チロシンヒドロキシラーゼの発現量の減少がMAK投与により正常に近づいたことが、嚥下障害改善効果の一端を担っていると考えられた。   As a result, in rats (shown as “2” in the figure) in which bilateral common carotid arteries were ligated and administered distilled water for 2 weeks after the surgery, sham surgery without ligating the common carotid artery was performed, and then distilled water was used for 2 weeks. The amount of tyrosine hydroxylase expressed in the striatum was decreased compared to the rat administered with (1) in the figure. On the other hand, in the rats (indicated by “3” in the figure) in which bilateral common carotid artery was ligated and MAK was administered for 2 weeks after the operation, the expression level was restored to the same level as in the sham-operated rats. Therefore, it was considered that the decrease in the expression level of tyrosine hydroxylase approached normal by MAK administration was partly responsible for the effect of improving dysphagia.

(3)培養培地抽出物のその他の調製例
<調製例2>(バガスを用いた椎茸菌の固体培養)
バガス80質量部と、脱脂米糠20質量部とを配合し、水分70%となるように調整して固体培地を作り、常法通り高圧蒸気滅菌した。この固体培地に椎茸の菌糸を接種し、22〜24℃に温度調節した培養室内で4か月間培養し、培地中に菌糸体が蔓延した後、温度処理室に移して32〜34℃で24時間加温し、次いで10℃の低温室で5日間処理した。その後、上記培養室で2日間培養し、培地を破砕機で2回破砕した。破砕した培地を50℃で4時間処理し、自己消化を促進させた後、抽出タンクに詰め、60℃の温水を循環させながら16時間抽出した。得られた抽出液を珪藻土のフィルターケーキで予備濾過し、更にメンブランフィルターで濾過除菌後、濃縮し、凍結乾燥により褐色の粉末を得た。その成分を分析した結果は以下の通りであった。
(3) Other Preparation Examples of Culture Medium Extract <Preparation Example 2> (Solid culture of Shiitake mushroom using bagasse)
80 parts by mass of bagasse and 20 parts by mass of defatted rice bran were blended, adjusted to a moisture content of 70%, a solid medium was prepared, and autoclaved as usual. This solid medium was inoculated with shiitake mycelia and cultured for 4 months in a culture chamber adjusted to a temperature of 22 to 24 ° C. After the mycelium invaded in the medium, it was transferred to a temperature treatment chamber at 24 to 34 ° C. Warm for hours and then treat in a cold room at 10 ° C. for 5 days. Then, it culture | cultivated for 2 days in the said culture room, and the culture medium was crushed twice with the crusher. The crushed medium was treated at 50 ° C. for 4 hours to promote autolysis, then packed in an extraction tank, and extracted for 16 hours while circulating 60 ° C. warm water. The obtained extract was pre-filtered with a filter cake made of diatomaceous earth, further filtered and sterilized with a membrane filter, concentrated, and freeze-dried to obtain a brown powder. The results of analyzing the components were as follows.

・糖質 :35%(フェノール硫酸法)
・蛋白質 :12%(セミミクロケルダール法)
・水溶性リグニン :35%(アセチルブロマイド法)
・無機質 :13%(直接灰化法)
・ Carbohydrate: 35% (phenol sulfate method)
・ Protein: 12% (semi-micro Kjeldahl method)
・ Water-soluble lignin: 35% (acetyl bromide method)
・ Inorganic: 13% (direct ashing method)

<調製例3>(トウモロコシの茎を用いた椎茸菌の固体培養)
トウモロコシの茎を水洗いし乾燥した後、破砕し、米糠を質量比で2割加え、水分70%となるように調整して固体培地を作り、常法通り高圧蒸気滅菌した。この固体培地に椎茸の菌糸を接種し、調製例2と同様にして培養抽出物を得た。その成分を分析した結果は以下の通りであった。
<Preparation Example 3> (Solid culture of Shiitake mushroom using corn stalk)
Corn stalks were washed with water, dried, crushed, and rice bran was added at a mass ratio of 20%, adjusted to 70% moisture, a solid medium was prepared, and autoclaved as usual. Shiitake mycelium was inoculated into this solid medium, and a culture extract was obtained in the same manner as in Preparation Example 2. The results of analyzing the components were as follows.

・糖質 :40%(フェノール硫酸法)
・蛋白質 :12%(セミミクロケルダール法)
・水溶性リグニン :35%(アセチルブロマイド法)
・無機質 :12%(直接灰化法)
・ Sugar: 40% (phenolic sulfuric acid method)
・ Protein: 12% (semi-micro Kjeldahl method)
・ Water-soluble lignin: 35% (acetyl bromide method)
・ Inorganic: 12% (direct ashing method)

<調製例4>(熊笹を用いたマンネン茸菌の固体培養)
熊笹の色素、香りをエチルアルコールで抽出した繊維残渣を破砕したものに米糠を質量比で1割加え、水分70%となるように調整して固体培地を作り、常法通り高圧蒸気滅菌した。この固体培地にマンネン茸の菌糸を接種し、調製例2と同様にして培養抽出物を得た。その成分を分析した結果は以下の通りであった。
<Preparation Example 4> (Solid culture of N. gonorrhoeae using Kumagusu)
10% by mass of rice bran was added to the crushed fiber residue obtained by extracting the pigment and scent of kumabuchi with ethyl alcohol, and a solid medium was prepared by adjusting the water content to 70%, followed by high-pressure steam sterilization as usual. This solid medium was inoculated with mycelium of mannen koji, and a culture extract was obtained in the same manner as in Preparation Example 2. The results of analyzing the components were as follows.

・糖質 :30%(フェノール硫酸法)
・蛋白質 :15%(セミミクロケルダール法)
・水溶性リグニン :35%(アセチルブロマイド法)
・無機質 :10%(直接灰化法)
・ Sugar: 30% (phenolic sulfuric acid method)
・ Protein: 15% (semi-micro Kjeldahl method)
・ Water-soluble lignin: 35% (acetyl bromide method)
・ Inorganic: 10% (direct ashing method)

<調製例5>(バガスを用いた椎茸菌の液体培養)
水1L(リットル)に対し、ミキサーで細かく破砕したバガス60g、乾燥オカラ20g、米糠20g、イーストエキス2gを加え、常法通り高圧蒸気滅菌した。この液体培地に椎茸の菌糸を接種し、23℃で3週間通気培養した後、培養液を60℃で1時間、80℃で2時間加温し、菌糸の酵素による自己消化反応を進行させると共に代謝物を抽出させた。培養液は3,000rpmで30分間遠心分離し、沈殿物を除き、褐色の液を得た。この抽出液を凍結乾燥し、分析した結果は、以下の通りであった。
<Preparation Example 5> (Liquid culture of Shiitake mushroom using bagasse)
To 1 L (liter) of water, 60 g of bagasse finely crushed with a mixer, 20 g of dried okara, 20 g of rice bran, and 2 g of yeast extract were added, followed by high-pressure steam sterilization as usual. This liquid medium is inoculated with mycelia of shiitake mushrooms and aerated for 3 weeks at 23 ° C., and then the culture solution is heated at 60 ° C. for 1 hour and at 80 ° C. for 2 hours to promote the self-digestion reaction of the mycelium enzyme Metabolites were extracted. The culture solution was centrifuged at 3,000 rpm for 30 minutes, the precipitate was removed, and a brown solution was obtained. The extract was lyophilized and analyzed, and the results were as follows.

・糖質 :38%(フェノール硫酸法)
・蛋白質 :16%(セミミクロケルダール法)
・水溶性リグニン :35%(アセチルブロマイド法)
・その他 :11%
・ Carbohydrate: 38% (phenol sulfate method)
・ Protein: 16% (semi-micro Kjeldahl method)
・ Water-soluble lignin: 35% (acetyl bromide method)
・ Other: 11%

<調製例6>(熊笹を用いたマンネン茸菌の液体培養)
熊笹の色素、香りをエチルアルコールで抽出した繊維残渣をミキサーで細かく破砕したものを水1Lに対し90g、米糠10g、イーストエキス5gを加え、常法通り高圧蒸気滅菌した。この液体培地にマンネン茸の菌糸を接種して、23℃で2週間通気培養を行った。培養物は、調製例4と同様の方法で加熱、遠心処理し、濃褐色の液を得た。この抽出液を凍結乾燥し、分析した結果は、以下の通りであった。
<Preparation Example 6> (Liquid culture of gonococcus manneum using bear candy)
90 g, 10 g of rice bran, and 5 g of yeast extract were added to 1 L of water and the fiber residue obtained by extracting the pigment residue and fragrance of Kumagusu with ethyl alcohol finely with a mixer was sterilized under high pressure steam as usual. This liquid medium was inoculated with mycelium of mannen koji, and aerated at 23 ° C. for 2 weeks. The culture was heated and centrifuged in the same manner as in Preparation Example 4 to obtain a dark brown liquid. The extract was lyophilized and analyzed, and the results were as follows.

・糖質 :33%(フェノール硫酸法)
・蛋白質 :18%(セミミクロケルダール法)
・水溶性リグニン :40%(アセチルブロマイド法)
・その他 : 9%
・ Carbohydrate: 33% (phenol sulfate method)
・ Protein: 18% (semi-micro Kjeldahl method)
・ Water-soluble lignin: 40% (acetyl bromide method)
・ Others: 9%

<調製例7>(バガスを用いたヤマブシ茸の固体培養)
バガス65質量部、小麦ふすま20質量部、米糠10質量部、乾燥イースト5質量部を配合し、水分70%となるように調整して固体培地を作り、常法通り高圧蒸気滅菌した。この固体培地にヤマブシ茸の菌糸を接種し、調製例2と同様にして培養抽出物を得た。その成分を分析した結果は以下の通りであった。
<Preparation Example 7> (Solid culture of Yamabushi persimmon using bagasse)
65 parts by mass of bagasse, 20 parts by mass of wheat bran, 10 parts by mass of rice bran, and 5 parts by mass of dry yeast were mixed, adjusted to a moisture of 70%, a solid medium was prepared, and autoclaved as usual. This solid medium was inoculated with mycelium of Yamabushi mushroom, and a culture extract was obtained in the same manner as in Preparation Example 2. The results of analyzing the components were as follows.

・糖質 :43%(フェノール硫酸法)
・蛋白質 :12%(セミミクロケルダール法)
・水溶性リグニン :28%(アセチルブロマイド法)
・無機質 :10%
・ Carbohydrate: 43% (phenol sulfuric acid method)
・ Protein: 12% (semi-micro Kjeldahl method)
・ Water-soluble lignin: 28% (acetyl bromide method)
・ Inorganic: 10%

Claims (2)

バガス及び米糠を含む培地を用いてマンネン茸の菌糸体を培養し、その培養物から抽出して得た、糖質、蛋白質、及び水溶性リグニンを含む抽出物を有効成分として含有することを特徴とする嚥下障害改善剤。 It is characterized by containing, as an active ingredient, an extract containing saccharides, proteins and water-soluble lignin obtained by culturing mycelium of mannen koji using a medium containing bagasse and rice koji and extracting from the culture. A dysphagia improving agent. 前記抽出物は、前記培養物から、担子菌の自己消化を行って得られたものである請求項1記載の嚥下障害改善剤。   The dysphagia improving agent according to claim 1, wherein the extract is obtained by performing autolysis of basidiomycetes from the culture.
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