JP2015021002A - Agent for suppressing blood pressure elevation of fermented laminaria angustata kjellman obtained by using genus lactobacillus - Google Patents

Agent for suppressing blood pressure elevation of fermented laminaria angustata kjellman obtained by using genus lactobacillus Download PDF

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JP2015021002A
JP2015021002A JP2013161787A JP2013161787A JP2015021002A JP 2015021002 A JP2015021002 A JP 2015021002A JP 2013161787 A JP2013161787 A JP 2013161787A JP 2013161787 A JP2013161787 A JP 2013161787A JP 2015021002 A JP2015021002 A JP 2015021002A
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濱田 奈保子
Nahoko Hamada
奈保子 濱田
奈々子 二瓶
Nanako Nihei
奈々子 二瓶
矢澤 一良
Kazuyoshi Yazawa
一良 矢澤
宏 三沢
Hiroshi Misawa
宏 三沢
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NIPPON BIO CO Ltd
Shonan Inst For Medical & Preventive Science
Shonan Institute for Medical and Preventive Science
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NIPPON BIO CO Ltd
Shonan Inst For Medical & Preventive Science
Shonan Institute for Medical and Preventive Science
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Abstract

PROBLEM TO BE SOLVED: To provide an agent or a composition for suppressing blood pressure elevation containing, as an active ingredient, fermented Laminaria angustata Kjellman which is fermented by using genus Lactobacillus, the fermented Laminaria angustata Kjellman as well as Laminaria angustata Kjellman are traditionally eaten and safe.SOLUTION: There are provided: functional food, food materials and pet food, for preventing or improving blood pressure elevation containing, as an active ingredient, fermented Laminaria angustata Kjellman obtained by using genus Lactobacillus; and, as internal agents, compositions for pharmaceuticals (including pharmaceuticals for animals), for drink and food, and for feeding stuff, given to humans or non-human animals.

Description

本発明はLactobacillus属を用いた発酵ヒダカコンブを有効成分として含有する血圧上昇抑制作用に関する。
本発明は、血圧上昇抑制機能性食品または食品素材、内服剤として、ヒト若しくはヒト以外の動物に与えられる医薬品(動物用治療薬も含む)用、飲食品用、および飼料用またはペットフードの組成物を意味する。
The present invention relates to an antihypertensive action containing fermented hedaka kumbu using Lactobacillus genus as an active ingredient.
The present invention relates to a blood pressure increase-suppressing functional food or food material, or an internal preparation for pharmaceuticals (including animal therapeutics) given to humans or animals other than humans, for foods and drinks, and for feeds or pet foods. Means a thing.

高血圧は生活習慣病の一つである。高血圧は原因が分かっている二次性高血圧と原因がわからない本態性高血圧の二つがあるが、日本における高血圧患者の約90%が本態性高血圧である。血圧は、心拍出量と末梢血管抵抗その他さまざまな因子によって調節されており、なかでも、レニン・アンジオテンシン系は、血圧の制御に関して大きな役割を担っている。肝臓でアンジオテンシノーゲンが合成され、アンジオテンシノーゲンは腎臓で合成されるレニンによってアンジオテンシンIに変換さる。さらにアンジオテンシン変換酵素(ACE)によってアンジオテンシンIIへと変換される。アンジオテンシンIIがアンジオテンシンII受容体に結合することで、血管平滑筋が収縮し、結果として血圧が上昇する。高血圧は自覚症状がないため、放置してしまうことが多く、動脈硬化、心臓病、脳卒中を引き起こすことがある。Hypertension is one of lifestyle-related diseases. There are two types of hypertension: secondary hypertension whose cause is known and essential hypertension whose cause is unknown. About 90% of hypertensive patients in Japan have essential hypertension. Blood pressure is regulated by various factors such as cardiac output, peripheral vascular resistance, and the renin-angiotensin system plays a major role in controlling blood pressure. Angiotensinogen is synthesized in the liver, and angiotensinogen is converted to angiotensin I by renin synthesized in the kidney. Furthermore, it is converted into angiotensin II by angiotensin converting enzyme (ACE). By binding angiotensin II to the angiotensin II receptor, vascular smooth muscle contracts, resulting in an increase in blood pressure. Hypertension has no subjective symptoms and is often left unattended, which can cause arteriosclerosis, heart disease, and stroke.

前述の高血圧については、これを解消するための医療品が種々提案され、既に数多く市販されている。治療剤としては、腎臓でのナトリウムと水の再吸収を抑制し循環血液量を減少させて血圧を下げる利尿薬、交感神経のα受容体の血管収縮作用を遮断し血管を拡張させ血圧を下げるα遮断薬、交感神経のβ受容体の心臓収縮力強化や昇圧ホルモン産生などの作用を遮断して血圧を下げるβ遮断薬、カルシウムイオンの細胞内への取り込みを抑制し血管を拡張することで血圧を下げるカルシウム拮抗薬、強力な昇圧ホルモンであるアンジオテンシンIIの生産を減少させ、血圧を下げるアンジオテンシン変換酵素(ACE)阻害薬、昇圧ホルモンであるアンジオテンシンIIが作用する受容体の働きを阻害することで血圧を下げるアンジオテンシンII受容体阻害薬(ARB)が用いられるが、これら医療用合成製剤は、処方箋を必要とするため、簡易には入手できないばかりか、製剤の投与又は服用により種々の副作用を伴うことがある。従って、高血圧の治療に使用される抗高血圧剤として、入手が容易でかつ副作用ができるだけ少ない天然物起源のものが求められている。
天然物起源の高血圧の改善剤としては、ACE阻害を示すノリ、カツオ、ワカメなどのペプチド、副交感神経を刺激し血管平滑筋が弛緩され血圧が降下作用を示す杜中葉抽出物、ノルアドレナリンの分泌を抑制し血圧降下作用を示すγ−アミノ酪酸を配合特定保健用食品が知られており、これらは特定保健用食品としての承認を得ている。
Regarding the above-mentioned hypertension, various medical products for solving this problem have been proposed and many are already on the market. Therapeutic agents are diuretics that suppress the reabsorption of sodium and water in the kidneys and reduce the blood circulation to lower blood pressure, block the vasoconstrictive action of sympathetic alpha receptors and dilate blood vessels to lower blood pressure. α-blocker, β-blocker that lowers blood pressure by blocking the effects of sympathetic β-receptor enhancement of cardiac contraction and production of pressor hormones, suppresses calcium ion uptake into cells and dilates blood vessels Inhibiting the action of receptors acting on angiotensin II, an angiotensin II that lowers blood pressure, angiotensin-converting enzyme (ACE) inhibitor that lowers blood pressure, and reduces the production of calcium antagonist that lowers blood pressure, a powerful pressor hormone Angiotensin II receptor blocker (ARB) that lowers blood pressure is used, but these medical preparations require a prescription Not only not available easily, it may be accompanied by various side effects by administration or dosing of the formulation. Accordingly, natural anti-hypertensive agents used for the treatment of hypertension are demanded that are easily available and have as few side effects as possible.
As a natural hypertension ameliorating agent, peptides such as glue, bonito and seaweed that show ACE inhibition, parasympathetic nerves, vascular smooth muscles relax, blood pressure lowering action, noradrenaline secretion Specified health foods containing γ-aminobutyric acid that suppress and exhibit a blood pressure lowering action are known, and these have been approved as foods for specified health use.

本発明の課題は、日常の食生活において容易に入手および摂取でき、血圧上昇を抑制することができる、副作用の少ない予防・改善用機能性食品又は食品素材や、飼料を提供することにある。An object of the present invention is to provide a functional food or food material for prevention and improvement, which can be easily obtained and ingested in daily eating habits, and can suppress an increase in blood pressure, or a feed material, and feed.

本発明者は、上述の目的を達成するために、ヒダカコンブの機能性成分とLactobacillus属の機能性に着目し、鋭意研究を行った結果、Lactobacillus属を用いた発酵ヒダカコンブ80%EtOH抽出物に血圧上昇抑制作用があることを見出すに至った。In order to achieve the above-mentioned object, the present inventor has paid attention to the functional components of Hidaka Kombu and the functionality of the genus Lactobacillus, and as a result of intensive studies, the present inventors have determined that blood pressure is applied to an 80% EtOH extract of the fermented Hedaka Kombu using the Lactobacillus genus. It came to discover that there is an increase suppression effect.

本発明は、このような知見に基づいて完成されたものである。すなわち、本発明の血圧上昇抑制作用は、いずれも発酵ヒダカコンブを有効成分することを特徴とするものである。The present invention has been completed based on such findings. That is, the antihypertensive action of the present invention is characterized in that any fermented hawkweed is an active ingredient.

Lactobacillus属を用いた発酵ヒダカコンブに含まれる血圧上昇抑制作用を有する物質がいかなる化合物であるかについては、未だその詳細は不明であるが、発酵ヒダカコンブから80%EtOH抽出により溶出させた成分が血圧上昇抑制作用を発揮することは実験的に確かめられている。したがって、Lactobacillus属を用いた発酵ヒダカコンブは、そのまま本発明の血圧上昇抑制作用の構成成分とすることで予防・改善が発現する。Although it is still unclear what kind of compound the substance having an inhibitory effect on blood pressure increase contained in fermented hawkweed using Lactobacillus genus is, the components eluted from the fermented hawkweed by 80% EtOH extraction increased blood pressure. It has been experimentally confirmed that it exhibits an inhibitory action. Accordingly, fermented hawkweed using Lactobacillus genus can be prevented or improved by using it as a constituent component of the blood pressure elevation inhibiting action of the present invention as it is.

即ち本発明が提供するのは以下の通りである。That is, the present invention provides the following.

[1]Lactobacillus属を用いた発酵ヒダカコンブを有効成分として含有する。[1] A fermented hawk moth using Lactobacillus genus is contained as an active ingredient.

[2]Lactobacillus属を用いた発酵ヒダカコンブを含有する組成物を有効成分として含有する血圧上昇抑制剤。[2] An antihypertensive agent comprising, as an active ingredient, a composition containing fermented hidaka kombu using Lactobacillus genus.

[3][1]または[2]に記載の血圧上昇抑制剤からなる機能性食品。[3] A functional food comprising the antihypertensive agent according to [1] or [2].

[4][1]または[2]に記載の血圧上昇抑制剤からなる食品素材。[4] A food material comprising the antihypertensive agent according to [1] or [2].

[5][1]または[2]に記載の血圧上昇抑制剤からなるペットフード。[5] A pet food comprising the antihypertensive agent according to [1] or [2].

[6][1]または[2]に記載された血圧上昇抑制剤からなる飼料。[6] A feed comprising an antihypertensive agent described in [1] or [2].

[7][1]〜[4]に記載の血圧上昇抑制剤を含有する飲食用組成物。[7] A food and beverage composition containing the blood pressure elevation inhibitor according to [1] to [4].

[8][1]〜[4]に記載の血圧上昇抑制剤を含有する医薬用組成物。[8] A pharmaceutical composition containing the blood pressure elevation inhibitor according to [1] to [4].

本発明の血圧上昇抑制剤、またはこれを含有する組成物は、体内でアンジオテンシンIを、昇圧作用を持つアンジオテンシンIIに変換するACEの活性を抑制することから、血圧上昇抑制作用が期待できる。従って、血圧上昇抑制に有用である。さらに、食経験のある材料から本発明の剤または組成物を製造することが可能であるので、摂取しても安全である。The antihypertensive agent of the present invention or a composition containing the antihypertensive agent suppresses the activity of ACE that converts angiotensin I into angiotensin II having an antihypertensive action in the body, and therefore an antihypertensive action can be expected. Therefore, it is useful for suppressing an increase in blood pressure. Furthermore, since it is possible to produce the agent or composition of the present invention from ingredients with food experience, it is safe to take.

本明細書の血圧上昇抑制剤は、Lactobacillus属を用いた発酵ヒダカコンブを有効成分として含有するACE害作用を有する剤および組成物である。上記の化合物の含有量は限定されないが、血圧上昇抑制作用を発揮できる範囲で含まれていれば良い。The antihypertensive agent of the present specification is an agent and a composition having an ACE harmful effect, which contains fermented hidaka kombu using Lactobacillus genus as an active ingredient. Although content of said compound is not limited, it should just be contained in the range which can exhibit the blood pressure rise inhibitory effect.

本発明の飲食用組成物は、上記の血圧上昇抑制剤を含有する組成物であり、これらを一般的な食品に混合したものである。また、公知の食品として適当な担体や助剤などを使用してカプセル剤、錠剤、顆粒剤など服用しやすい形態にしたものでもよい。ここに言う飲食用とは、例えば、一般食品、保健機能食品(特定保健用食品、栄養機能食品)、健康食品、栄養補助食品、ペットフードなどである。ここにいう一般食品とは、飲料、乳製品、発酵乳、乳酸菌飲料、加工乳、コーヒー飲料、ジュース、アイスクリーム、飴、ビスケット、ウェハース、ゼリー、スープ、麺類、を含むがそれに限定されるものではない。好ましくは飲料、乳製品、加工乳、発酵乳、乳酸菌飲料、ウェハース、ゼリーを含む。The composition for eating and drinking of the present invention is a composition containing the above-mentioned blood pressure increase inhibitor, and these are mixed with general foods. Further, capsules, tablets, granules and the like that are easy to take may be used by using appropriate carriers and auxiliaries as known foods. The food and drink here refers to, for example, general foods, health functional foods (special health foods, nutritional functional foods), health foods, nutritional supplements, pet foods, and the like. General food as used herein includes, but is not limited to, beverages, dairy products, fermented milk, lactic acid bacteria beverages, processed milk, coffee beverages, juices, ice creams, strawberries, biscuits, wafers, jellies, soups, and noodles. is not. Preferably, beverages, dairy products, processed milk, fermented milk, lactic acid bacteria beverages, wafers, and jelly are included.

本発明の医薬用組成物は、上記の血圧上昇抑制剤を含有する組成物であり、上記剤そのものであってもよいし、所望により医薬的に許容される担体を含有する組成物であってもよい。その用途は限定されず、例えば一般用医薬品(OTC)など容易に入手可能な医薬品又は医薬部外品などが挙げられる。医薬用組成物の形態は限定されず、例えば、丸薬剤、液剤、粉末剤、顆粒剤、錠剤、カプセル錠剤、トローチ剤、シロップ剤、ドライシロップ剤などである。好ましくはカプセル剤、液剤、エリクシル、錠剤、カシェ、座薬などとするほうが良い。また医薬的に許容される担体とは、経口、経腸、経皮、および皮下投与のために好適である任意の材料であり、例えば水、ゼラチン、アラビアガム、ラクトース、微結晶性セルロース、スターチ、ナトリウムスターチグリコレート、燐酸水素カルシウム、ステアリン酸マグネシウム、タルク、コロイド性二酸化ケイ素などが挙げられる。The pharmaceutical composition of the present invention is a composition containing the above antihypertensive agent, may be the above agent itself, or a composition containing a pharmaceutically acceptable carrier as desired. Also good. The use is not limited, and examples thereof include readily available drugs such as over-the-counter drugs (OTC) or quasi drugs. The form of the pharmaceutical composition is not limited, and examples thereof include pills, solutions, powders, granules, tablets, capsule tablets, troches, syrups, and dry syrups. Preferably, capsules, liquids, elixirs, tablets, cachets, suppositories and the like are used. A pharmaceutically acceptable carrier is any material suitable for oral, enteral, transdermal, and subcutaneous administration, such as water, gelatin, gum arabic, lactose, microcrystalline cellulose, starch. Sodium starch glycolate, calcium hydrogen phosphate, magnesium stearate, talc, colloidal silicon dioxide and the like.

Lactobacillus属を用いた発酵ヒダカコンブならびに該組成物は、血圧上昇抑制剤の有効成分として配合されるが、血圧上昇抑制剤として製剤化する場合、剤形としては、粉末状、顆粒状、錠剤状等、任意の剤形を採用することができる。その際、保存や取り扱いを容易にするために、デキストリン、シクロデキストリン等のキャリヤ、保存料、その他任意の助剤を必要に応じて配合することができる。またその形態は限定されず、飲食用組成物、医薬用組成物を含む。これらの含有量は限定されないが、血圧上昇抑制作用に対して効果が発揮できる範囲で含まれていれば良い。The fermented hedaka kumbu using Lactobacillus genus and the composition are blended as an active ingredient of an antihypertensive agent, but when formulated as an antihypertensive agent, the dosage form includes powder, granules, tablets, etc. Any dosage form can be employed. At that time, in order to facilitate storage and handling, carriers such as dextrin and cyclodextrin, preservatives and other optional auxiliaries can be blended as necessary. Moreover, the form is not limited, The composition for food and drink and the composition for medicine are included. Although these content is not limited, it should just be contained in the range which can exhibit an effect with respect to a blood pressure rise inhibitory effect.

前記血圧上昇抑制剤は、ACEの活性を阻害してアンジオテンシンIIが生成されないようにする。The antihypertensive agent inhibits the activity of ACE so that angiotensin II is not generated.

Lactobacillus属を用いた発酵ヒダカコンブを有効成分として含有する本発明の血圧上昇の予防・改善用機能性食品又は食品素材は、前記本発明の血圧上昇の予防・改善剤を飲食品原料の一部として用いたり、あるいは製造工程又は製造後に添加・配合することにより得ることができる。かかる機能性食品としては特に制限されるものではなく、調味類、ふりかけ類、菓子類、スナック類、麺類、魚肉練り製品、乳製品、飲料などを具体的に例示することができる。The functional food or food material for preventing or improving blood pressure increase according to the present invention containing fermented hedaka kombu using Lactobacillus genus as an active ingredient, the blood pressure increase preventive / ameliorating agent according to the present invention as a part of a raw material for food and drink It can be obtained by use, or by adding and blending after the production process or production. Such functional foods are not particularly limited, and specific examples include seasonings, sprinkles, confectionery, snacks, noodles, fish paste products, dairy products, beverages, and the like.

実施例1
以下に本発明をより詳細に説明する為に実施例を挙げるが、本発明はこれらによって何ら限定されるものではない。
Example 1
Examples are given below to describe the present invention in more detail, but the present invention is not limited by these.

サンプルは500μm程度に粉砕したヒダカコンブ粉末5gを100mlのpH5.0の1/30Mリン酸緩衝液に加え、pHを5.0に調整後、50mgのセルラーゼを加え45℃、120rpmで振とう処理を行った。1〜2日間処理した後に、pH6.8に調整し加圧加熱滅菌を行った。海藻酵素処理液にLactobacillus属を1ml植菌し、37℃で静置培養した。4日間培養後凍結乾燥を行い、発酵ヒダカコンブ1gに100mlのエタノールを添加し、室温で3時間振とうしたものの上清をサンプルとした。For the sample, add 5 g of Hidaka Kombu powder pulverized to about 500 μm to 100 ml of 1/30 M phosphate buffer with a pH of 5.0, adjust the pH to 5.0, add 50 mg of cellulase, and shake at 45 ° C. and 120 rpm. went. After treatment for 1 to 2 days, the mixture was adjusted to pH 6.8 and sterilized under pressure and heat. 1 ml of Lactobacillus genus was inoculated into the seaweed enzyme-treated solution, followed by stationary culture at 37 ° C. After culturing for 4 days, freeze-drying was carried out, and 100 ml of ethanol was added to 1 g of fermented hidingweed kombu and shaken at room temperature for 3 hours to obtain a supernatant.

Lactobacillus属を用いた発酵ヒダカコンブのACE活性阻害作用に関する検討
Lactobacillus属を用いた発酵ヒダカコンブのACE活性への影響について、試験管内での酵素反応系を用いて検討した。蒸留水で希釈した各濃度のサンプル溶液10μlを添加し全量を130μl/反応ウェルとした。
Study on the ACE activity inhibitory action of fermented hawkweed using Lactobacillus genus The influence on the ACE activity of fermented hawkweed using genus Lactobacillus was examined using an enzyme reaction system in a test tube. 10 μl of sample solution of each concentration diluted with distilled water was added to make a total volume of 130 μl / reaction well.

本試験は(株)同仁化学研究所のACE Kit−WSTを使用した。本試験の反応に用いた溶液(A〜C液)は、以下のとおり調製した。A液はキット付属のSubstrate bufferである。B液はキット付属のEnzyme Bを2mlの蒸留水で溶解し、溶解した酵素液1.5mlをキット付属品のEnzyme Aに加え溶解した。C液はキット付属のEnzyme Cを3mlの蒸留水で溶解した。同じくキット付属のCoenzymeを3mlの蒸留水で溶解した。溶解したEnzyme CとCoenzymeをそれぞれ2.8mlずつキット付属のIndicator solutionに添加した。This test used ACE Kit-WST of Dojindo Laboratories. The solutions (A to C solutions) used for the reaction in this test were prepared as follows. A liquid is Substrate buffer attached to the kit. For solution B, Enzyme B attached to the kit was dissolved in 2 ml of distilled water, and 1.5 ml of the dissolved enzyme solution was dissolved in Enzyme A attached to the kit. The solution C was obtained by dissolving Enzyme C attached to the kit with 3 ml of distilled water. Similarly, Coenzyme included in the kit was dissolved in 3 ml of distilled water. Each 2.8 ml of dissolved Enzyme C and Coenzyme was added to the Indicator solution included in the kit.

プレート内でのACE反応は、各濃度に希釈したサンプル10μl、A液10μlとB液10μlを混合し、37℃で1時間プレインキュベーションした。次にC液100μlを加えて室温で10分間インキュベーションすることで実施させた。その後、450nmの吸光度を測定することでACE活性阻害を評価した。コントロールは、サンプルの代わりに各サンプルと同等の80%エタノールを添加した。各試験区には、B液の代わりにA液を添加したブランクを設定した。
阻害率は以下の計算式から求めた。阻害率=1−(サンプルの吸光度−サンプルのブランクの吸光度)/(コントロールの吸光度−コントロールのブランクの吸光度)。コントロールを100として溶媒と濃度に関連して、相対的のACE阻害率を図1に示した。
In the ACE reaction in the plate, 10 μl of sample diluted to each concentration, 10 μl of solution A and 10 μl of solution B were mixed and preincubated at 37 ° C. for 1 hour. Next, 100 μl of solution C was added and incubated at room temperature for 10 minutes. Thereafter, inhibition of ACE activity was evaluated by measuring absorbance at 450 nm. As a control, 80% ethanol equivalent to each sample was added instead of the sample. In each test group, a blank in which solution A was added instead of solution B was set.
The inhibition rate was calculated from the following calculation formula. Inhibition rate = 1- (absorbance of sample-absorbance of sample blank) / (absorbance of control-absorbance of control blank). The relative ACE inhibition rate in relation to the solvent and concentration is shown in FIG.

ACE阻害率をもとに50%阻害濃度であるIC50値を算出した。その結果を表1に表す。Based on the ACE inhibition rate, an IC 50 value that is a 50% inhibition concentration was calculated. The results are shown in Table 1.

表1からLactobacillus属を用いた発酵ヒダカコンブにACE活性阻害が認められた。なかでも最もACE活性阻害が高かったのはLactobacillus casei(L.casei)を用いた発酵ヒダカコンブで、IC50は、63μg/mlであった。また発酵前のヒダカコンブ80%エタノール抽出物におけるIC50は、690μg/mlであった。したがって、Lactobacillus属を用いた発酵ヒダカコンブはACE活性の阻害に有効であることが実証された。From Table 1, inhibition of ACE activity was observed in fermented hawkweeds using Lactobacillus genus. Among them, the highest inhibition of ACE activity was fermented hawkweed using Lactobacillus casei (L. casei), and the IC 50 was 63 μg / ml. Further, the IC 50 in the 80% ethanol extract of Hidaka Kumbu before fermentation was 690 μg / ml. Therefore, it has been demonstrated that fermented hawkweed using Lactobacillus genus is effective in inhibiting ACE activity.

L.caseiを用いた発酵ヒダカコンブによる効果を示すグラフであり、コントロールを100とする相対的ACE阻害率を示した。L. It is a graph which shows the effect by fermented hedaka kumbu using casei, and showed the relative ACE inhibition rate which makes control 100. アンジオテンシンIを負荷させたマウスに本発明の発酵ヒダカコンブ(2000mg/kg)を投与したときの血圧上昇値を示す図である。It is a figure which shows the blood-pressure raise value when the fermented hedaka kumbu (2000 mg / kg) of this invention is administered to the mouse | mouth which loaded angiotensin I. アンジオテンシンIを負荷させたマウスに本発明の発酵ヒダカコンブ(1000、2000、4000mg/kg)を投与したときの血圧上昇値を示す図である。It is a figure which shows the blood-pressure rise value when the fermented hedaka-comb (1000, 2000, 4000 mg / kg) of this invention is administered to the mouse | mouth which loaded angiotensin I. SHRに本発明の発酵ヒダカコンブを投与したときの血圧変化を示す図である。It is a figure which shows a blood pressure change when the fermented hedaka kumbu of this invention is administered to SHR.

実施例2
マウスに発酵ヒダカコンブを単回投与したときの血圧上昇抑制効果
条件:6週齢のddYマウス(雄性)を用い、1群8匹で単回投与を実施した。試料は発酵ヒダカコンブを2000mg/kg体重となるように調製した。試料を経口投与し、投与30分後にアンジオテンシンI(150μg/kg;和光純薬工業)を腹腔内に投与した。
Example 2
Suppressive effect on increase in blood pressure when a single dose of fermented hida kumbu was administered to mice: Six-week-old ddY mice (male) were used, and a single administration was carried out with 8 mice per group. The sample was prepared such that fermented hedaka kumbu was 2000 mg / kg body weight. The sample was orally administered, and 30 minutes after administration, angiotensin I (150 μg / kg; Wako Pure Chemical Industries) was intraperitoneally administered.

試料の調製法は以下の通りである。L.caseiを用いて4日間発酵させた発酵ヒダカコンブを凍結乾燥し、その乾燥粉末を80%エタノールで振盪させながら3時間抽出した。その抽出液からエタノールを除去したものを蒸留水に溶解させ濃度を調整した。The sample preparation method is as follows. L. The fermented hawkweed fermented with casei for 4 days was lyophilized, and the dried powder was extracted for 3 hours while shaking with 80% ethanol. The extract from which ethanol was removed was dissolved in distilled water to adjust the concentration.

血圧測定には、マウス・ラット用無加温型非観血式血圧計(BLOOD PRESSURE MONITOR FOR MICE&RAT Model MK−2000)を使用し、マウスの尾動脈収縮期血圧(SBP)を測定した。マウスの尾部をカフで締め付け、Tail−cuff法によりSBPを6回測定し、その平均値を求めた。アンジオテンシンI投与前後のSBPの差から、血圧上昇値を求めた。For blood pressure measurement, an unheated non-invasive blood pressure monitor for mice and rats (BLOOD PRESURE MONITOR FOR MICE & RAT Model MK-2000) was used to measure the tail artery systolic blood pressure (SBP) of the mouse. The tail of the mouse was clamped with a cuff, and SBP was measured 6 times by the tail-cuff method, and the average value was obtained. From the difference in SBP before and after angiotensin I administration, an increase in blood pressure was determined.

試料2000mg/kg投与時において、発酵ヒダカコンブ投与群は蒸留水投与のコントロール群に対して有意(p<0.001)にアンジオテンシンI負荷による血圧上昇を抑制した(図2)。また試料を0、1000、2000、4000mg/kgに調製し、同様に収縮期血圧上昇値を求めたところ、2000、4000mg/kgにおいて有意(p<0.05)に血圧上昇を抑制し、濃度依存性もみられた(図3)。At the time of administration of the sample of 2000 mg / kg, the fermented hidaka-comb administration group significantly (p <0.001) suppressed the increase in blood pressure due to angiotensin I load compared to the control group administered with distilled water (FIG. 2). Samples were prepared at 0, 1000, 2000, and 4000 mg / kg, and similarly, the systolic blood pressure increase value was obtained. At 2000 and 4000 mg / kg, the blood pressure increase was significantly suppressed (p <0.05), and the concentration was increased. Dependence was also seen (Figure 3).

実施例3
高血圧自然発症ラット(SHR)に発酵ヒダカコンブを連続投与したときの血圧変化
条件:6週齢のSHR(雄性)を用い、1群6匹で連続投与を実施した。飼料に5%の発酵ヒダカコンブを混ぜて自由摂取させ、35日間飼育した。対照群、発酵ヒダカコンブ群とともに飼料には食塩を1%となるように添加した。今回調製した発酵ヒダカコンブを投与することにより、投与35日目には有意(p<0.001)に血圧上昇を抑制していることがわかった(図4)。
Example 3
Blood pressure change conditions when fermented hidaka kumbu was continuously administered to spontaneously hypertensive rats (SHR): 6 weeks old SHR (male) was used, and 6 groups were continuously administered. The feed was admixed with 5% fermented hidakakonbu and allowed to freely ingest, and was bred for 35 days. Salt was added to the feed so as to be 1% together with the control group and the fermented hida kumbu group. It was found that administration of the fermented hedaka kumbu prepared this time significantly suppressed the increase in blood pressure on the 35th day of administration (p <0.001) (FIG. 4).

Claims (8)

Lactobacillus属を用いた発酵ヒダカコンブを有効成分として含有する血圧上昇抑制剤。An antihypertensive agent comprising fermented hedaka kumbu using Lactobacillus genus as an active ingredient. Lactobacillus属を用いた発酵ヒダカコンブを含有する組成物を有効成分として含有する血圧上昇抑制剤。An antihypertensive agent comprising, as an active ingredient, a composition containing fermented hidaka kombu using Lactobacillus genus. [1]または[2]に記載の血圧上昇抑制剤からなる機能性食品。A functional food comprising the antihypertensive agent according to [1] or [2]. [1]または[2]に記載の血圧上昇抑制剤からなる食品素材。A food material comprising the antihypertensive agent according to [1] or [2]. [1]または[2]に記載の血圧上昇抑制剤からなるペットフード。A pet food comprising the antihypertensive agent according to [1] or [2]. [1]または[2]に記載された血圧上昇抑制剤からなる飼料。A feed comprising the blood pressure increase inhibitor described in [1] or [2]. [1]〜[4]に記載の血圧上昇抑制剤を含有する飲食用組成物。A composition for eating and drinking containing the blood pressure elevation inhibitor according to [1] to [4]. [1]〜[4]に記載の血圧上昇抑制剤を含有する医薬用組成物。[1] A pharmaceutical composition comprising the blood pressure elevation inhibitor according to [4].
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