JP4707839B2 - Diabetes prevention and treatment - Google Patents
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Description
【０００１】
【発明の属する技術分野】
本発明は、糖尿病を発症した患者の食餌療法等による治療、及び糖尿病の危険因子を有する者の糖尿病発症の予防を目的とした糖尿病予防治療剤に関する。
【０００２】
更に詳しくは、本発明は、炭素数２０のモノエン酸及び／又はその誘導体、並びに炭素数２２のモノエン酸及び／又はその誘導体を有効成分として含有する糖尿病予防治療剤に関するものである。
【０００３】
【従来の技術】
従来、生活習慣病の一種である糖尿病を発症した患者用の栄養組成物の脂肪源として、オレイン酸等の単不飽和脂肪酸（モノエン酸）を含有する高オレインひまわり油等を使用することが知られている（特開平８−６７６３０号公報。以下、従来技術１と記載する。）。
しかしながら、これらの従来技術には、次に記載するとおりの不都合があった。
【０００４】
【発明が解決しようとする課題】
前記従来の技術に開示されているとおり、モノエン酸を含有する糖尿病患者用の栄養組成物が開発されていた。しかしながら、従来技術１には、モノエン酸に糖尿病の予防及び治療効果があることについては開示されていない。更に、従来技術１の糖尿病患者用の栄養組成物は、モノエン酸として、炭素数１８のオレイン酸を主に含有する油脂を使用しており、糖尿病の予防及び治療に、高級モノエン酸である炭素数２０のモノエン酸及び／又はその誘導体、並びに炭素数２２のモノエン酸及び／又はその誘導体を組み合わせて使用すること、更にこれらを特定の重量比で使用することは、一切検討されていなかった。
【０００５】
本発明者らは、前記従来技術に鑑みて、糖尿病の予防及び治療効果の高いモノエン酸の種類及びその組み合わせを見い出し、糖尿病予防治療剤を開発することを目的とし、種々のモノエン酸について試験を行った。
【０００６】
その結果、炭素数２０のモノエン酸及び／又はその誘導体、並びに炭素数２２のモノエン酸及び／又はその誘導体を組み合わせて使用することが、後記する試験例の結果からも明らかなとおり、従来の比較的低級なモノエン酸である炭素数１８のオレイン酸を主に含有する油脂を使用する場合に比較して、糖尿病の予防及び治療効果が高いことを見い出し、本発明を完成した。
本発明の目的は、新規な糖尿病の予防剤及び治療剤を提供することである。
【０００７】
【課題を解決するための手段】
前記課題を解決する本発明は、炭素数２０のモノエン酸と、炭素数２０のモノエン酸とアルカリ金属との塩と、炭素数２０のモノエン酸と低級脂肪族アルコールとのエステルと、炭素数２０のモノエン酸のモノ、ジ又はトリグリセライドとからなる群から選択される少なくとも１種、並びに炭素数２２のモノエン酸と、炭素数２２のモノエン酸とアルカリ金属との塩と、炭素数２２のモノエン酸と低級脂肪族アルコールとのエステルと、炭素数２２のモノエン酸のモノ、ジ又はトリグリセライドとからなる群から選択される少なくとも１種を有効成分として含有する糖尿病予防治療剤であり、炭素数２０のモノエン酸と、炭素数２０のモノエン酸とアルカリ金属との塩と、炭素数２０のモノエン酸と低級脂肪族アルコールとのエステルと、炭素数２０のモノエン酸のモノ、ジ又はトリグリセライドとからなる群から選択される少なくとも１種１重量部に対し、炭素数２２のモノエン酸と、炭素数２２のモノエン酸とアルカリ金属との塩と、炭素数２２のモノエン酸と低級脂肪族アルコールとのエステルと、炭素数２２のモノエン酸のモノ、ジ又はトリグリセライドとからなる群から選択される少なくとも１種の比率が、０．３乃至１７重量部であること（以下、態様１と記載する。）を望ましい態様としてもいる。
【０００８】
【発明の実施の形態】
次に、本発明について詳細に説明する。
本発明の糖尿病予防治療剤の有効成分である炭素数２０のモノエン酸及び／又はその誘導体、並びに炭素数２２のモノエン酸及び／又はその誘導体は、具体的には、炭素数２０のゴンドイン酸（ゴンドウ酸）、ガドレイン酸、５−イコセン酸等のイコセン酸（エイコセン酸）及び／又はその誘導体、並びに炭素数２２のエルカ酸（エルシン酸）、セトレイン酸、５−ドコセン酸等のドコセン酸及び／又はその誘導体である。
【０００９】
本発明に使用される高級モノエン酸である炭素数２０のモノエン酸、並びに炭素数２２のモノエン酸は、医薬的又は食品的に許容されるものであれば特に制限はなく、これらの高級モノエン酸の含有量が多い天然油脂、例えば、さめ肝油、鯨油、たら肝油、なたね油、からし油、キャベツ種子油、ホホバ油、メドウフォーム油等を、そのまま又は適宜組み合わせて使用することが可能であり、また、これらの天然油脂から、イコセン酸又はドコセン酸を常法、例えば分別蒸留、結晶化、溶媒抽出、尿素包接化、又はクロマトグラフィーにより抽出、精製して使用することも可能である。尚、簡便には、市販のゴンドイン酸、又はエルカ酸（いずれもシグマ社製）を使用することができる。
【００１０】
本発明に使用される高級モノエン酸である炭素数２０のモノエン酸、並びに炭素数２２のモノエン酸の誘導体、いわゆる高級モノエン酸の誘導体には、高級モノエン酸の塩のほか、種々のエステル等の誘導体を包含する。具体的には、ナトリウム、カリウム等のアルカリ金属との塩、メタノール、エタノール等の低級脂肪族アルコールとのエステル、モノ、ジ、又はトリグリセライド等を例示することができる。
【００１１】
また、本発明の態様１に示すとおり、炭素数２０のモノエン酸及び／又はその誘導体１重量部に対して、炭素数２２のモノエン酸及び／又はその誘導体を０．３乃至１７重量部の重量比（以下、特定範囲の重量比と記載することがある。）で含有する油脂を有効成分とすることが、後記する試験例の結果からも明らかなとおり、特定範囲の重量比でない場合に比較して、糖尿病の予防及び治療効果が高いことから望ましい。
【００１２】
本発明の糖尿病予防治療剤は、投与方法として、例えば、静注、経口、経管、及び経腸によりヒト又は動物に投与することができ、これらの投与方法及び治療目的に応じて、一般的な医薬製剤の形態である各種の剤形が選択可能である。その代表的なものとして錠剤、丸剤、散剤、液剤、懸濁剤、乳剤、顆粒剤、カプセル剤、注射剤（液剤、懸濁剤等）等を例示することができる。
【００１３】
また、本発明の糖尿病予防治療剤は、食事療法用として、一般的な飲食品の形態である栄養組成物として摂食することができる。
【００１４】
本発明の糖尿病予防治療剤の有効投与量は経口投与の場合（食事療法の場合も同じ。）、マウスによる試験結果から、炭素数２０のモノエン酸及び／又はその誘導体、並びに炭素数２２のモノエン酸及び／又はその誘導体（以下、高級モノエン酸類と記載することがある。）からなる有効成分の量を基準として５〜４００ｍｇ／体重ｋｇ／１日であることが判明した。
【００１５】
また、本発明の糖尿病予防治療剤の有効成分である高級モノエン酸類は、マウスを用いた経口投与による急性毒性試験の結果、毒性が極めて低く、ＬＤ50は１０ｇ／体重ｋｇ以上であり、ヒト又は動物に対して安全に、かつ副作用が極めて少ない状態で使用することができる。
【００１６】
更に、本発明の糖尿病予防治療剤は、他のモノエン酸、多価不飽和脂肪酸等の糖尿病の予防及び治療効果を有する物質と組み合わせて使用することも可能である。特に、炭素数２４のモノエン酸及び／又はその誘導体を含有することが、糖尿病の予防及び治療効果を相乗的に高めることから望ましい。
【００１７】
また、炭素数２４のモノエン酸及び／又はその誘導体の含有量は、本発明の態様１の糖尿病予防治療剤中の炭素数２０のモノエン酸及び／又はその誘導体１重量部に対して、炭素数２４のモノエン酸及び／又はその誘導体０．１乃至１０重量部の重量比で含有することが、糖尿病の予防及び治療効果を相乗的に一層高めることから望ましい。即ち、炭素数２０のモノエン酸及び／又はその誘導体１重量部に対して、炭素数２２のモノエン酸及び／又はその誘導体を０．３乃至１７重量部、並びに炭素数２４のモノエン酸及び／又はその誘導体０．１乃至１０重量部の重量比で含有する油脂を有効成分とする糖尿病予防治療剤が糖尿病の予防及び治療効果を一層高めることから望ましい。
【００１８】
尚、炭素数２４のモノエン酸及び／又はその誘導体は、具体的には、炭素数２４のネルボン酸（セラコレイン酸、鮫油酸）等のテトラコセン酸及び／又はその誘導体である。
【００１９】
次に試験例を示して本発明を詳細に説明する。
試験例１
この試験は、血糖値を指標として、従来技術と本発明を比較するために行った。
（１）試料の調製
市販のマウス用飼料（ＣＲＦ−１。オリエンタル酵母工業社製）に、次の各試験試料に示す成分を１％（重量。以下、特に断りのない限り同じ。）の割合で添加し、１２種類の試料を調製した。
試料１：本発明の炭素数２０のモノエン酸であるゴンドイン酸１重量部及び炭素数２２のモノエン酸であるエルカ酸１重量部からなる高級モノエン酸混合物
試料２：ゴンドイン酸
試料３：エルカ酸
試料４：炭素数１８のオレイン酸
試料５：オレイン酸１重量部及びエルカ酸１重量部からなるモノエン酸混合物
試料６：オレイン酸１重量部及びゴンドイン酸１重量部からなるモノエン酸混合物
試料７：従来技術１のオリーブ油
試料８：従来技術１のキャノラ油
試料９：従来技術１の高オレイン紅花油
試料10：従来技術１の高オレインひまわり油
試料11：従来技術１の大豆油
試料12：対照としてのラード
尚、ゴンドイン酸、エルカ酸、及びオレイン酸はいずれも市販品（シグマ社製）を使用した。また、オリーブ油、キャノラ油、高オレイン紅花油、高オレインひまわり油、及び大豆油はいずれも市販品（日清製油社製）を使用した。更に、ラードは市販品（太陽油脂社製）を使用した。
【００２０】
（２）試験方法
糖尿病モデル動物として、食欲中枢異常により、過食による高血糖値を示すことが知られているＣ５７ＢＬ／ＫｓＪ−ｄｂ／ｄｂマウス（８週齢の雄。以下、ｄｂマウスと記載する。日本チャールスリバー社から入手。）を各試験群当たり７匹使用した。
【００２１】
各試験群の各マウスに前記１２種類の試料及び水を自由に摂取させ、４週間、即ち１２週齢まで飼育し、のち血液を採取し、次の方法により血糖値を測定し、試験開始時（８週齢）及び試料１２の対照群の血糖値と比較して糖尿病の予防及び治療効果を評価して試験した。
血糖値は、注射用シリンジを使用してマウス尾静脈から、少量の血液を採取し、市販のグルテストセンサー（三和化学研究所社製）を使用して測定した。
【００２２】
（３）試験結果
この試験の結果は、表１に示すとおりである。表１から明らかなとおり、本発明の高級モノエン酸混合物試料１は、試験開始時（８週齢）の血糖値（４６０ｍｇ／ｄｌ）及び試験試料としてラード（太陽油脂社製）を使用した対照群（試料12）の血糖値と比較して顕著な血糖値の低下が認められ、即ち糖尿病の予防及び治療効果が認められた。
【００２３】
また、本発明の高級モノエン酸混合物試料１は、従来技術１のモノエン酸として炭素数１８のオレイン酸を主に含有する油脂であるオリーブ油、キャノラ油、高オレイン紅花油、高オレインひまわり油、又は大豆油を使用した試料７乃至試料11に比較して、血糖値の低下作用に優れていること、即ち糖尿病の予防及び治療効果に優れていることが認められた。
【００２４】
更に、本発明の高級モノエン酸混合物試料１は、ゴンドイン酸の単独使用の試料２、エルカ酸の単独使用の試料３、及びオレイン酸の単独使用の試料４に比較して、血糖値の低下作用に優れており、また、試料１のゴンドイン酸をオレイン酸に置換したモノエン酸混合物である試料５及び試料１のエルカ酸をオレイン酸に置換したモノエン酸混合物である試料６に比較して、血糖値の低下作用に優れていることから、糖尿病の予防及び治療のためには、炭素数２０のモノエン酸であるゴンドイン酸及び炭素数２２のモノエン酸であるエルカ酸を組み合わせて使用すること、即ち、炭素数２０のモノエン酸及び／又はその誘導体、並びに炭素数２２のモノエン酸及び／又はその誘導体を組み合わせて使用することが有効であることが判明した。
【００２５】
尚、ゴンドイン酸に変えて炭素数２０のガドレイン酸、５−イコセン酸、若しくはこれらの誘導体、又はエルカ酸に変えて炭素数２２のセトレイン酸、５−ドコセン酸、若しくはこれらの誘導体を使用して試験したが、ほぼ同様の結果が得られた。また、試料１のモノエン酸の重量比を、ゴンドイン酸１重量部に対してエルカ酸０．３乃至１７重量部の範囲内で適宜変更して試験したが、ほぼ同様の結果が得られた。更に、試料５及び試料６のモノエン酸の重量比を適宜変更して試験したが、ほぼ同様の結果が得られた。
【００２６】
【表１】
試験例２
この試験は、血糖値を指標として、炭素数２０のモノエン酸及び／又はその誘導体、並びに炭素数２２のモノエン酸及び／又はその誘導体の重量比を調べるために行った。
（１）試料の調製
次に示す４種類の試料を前記試験例１と同一の方法により調製した。
試料13：炭素数２０のモノエン酸であるゴンドイン酸１重量部及び炭素数２２のモノエン酸であるエルカ酸０．２重量部からなる高級モノエン酸混合物
試料14：炭素数２０のモノエン酸であるゴンドイン酸１重量部及び炭素数２２のモノエン酸であるエルカ酸０．３重量部からなる高級モノエン酸混合物
試料15：炭素数２０のモノエン酸であるゴンドイン酸１重量部及び炭素数２２のモノエン酸であるエルカ酸１７重量部からなる高級モノエン酸混合物
試料16：炭素数２０のモノエン酸であるゴンドイン酸１重量部及び炭素数２２のモノエン酸であるエルカ酸１８重量部からなる高級モノエン酸混合物
【００２８】
（２）試験方法
各試料の糖尿病症の予防及び治療効果を、前記試験例１の試験方法により試験した。
【００２９】
（３）試験結果
この試験の結果は、表２に示すとおりである。表２から明らかなとおり、炭素数２０のモノエン酸であるゴンドイン酸１重量部に対して、炭素数２２のモノエン酸であるエルカ酸が０．３乃至１７重量部の重量比である場合に、血糖値の低下作用に一層優れていることから、糖尿病を一層有効に予防及び治療するためには、炭素数２０のモノエン酸及び／又はその誘導体１重量部に対する炭素数２２のモノエン酸及び／又はその誘導体の比率は、０．３乃至１７重量部が望ましい範囲であることが判明した。
【００３０】
尚、ゴンドイン酸に変えて炭素数２０のガドレイン酸、５−イコセン酸、若しくはこれらの誘導体、又はエルカ酸に変えて炭素数２２のセトレイン酸、５−ドコセン酸、若しくはこれらの誘導体を使用して試験したが、ほぼ同様の結果が得られた。
【００３１】
【表２】
次に実施例を示して本発明を更に詳細に説明するが、本発明は以下の実施例に限定されるものではない。
【００３３】
【実施例】
実施例１
ゴンドイン酸（シグマ社製）１５０ｇ及びエルカ酸（シグマ社製）１５０ｇの高級モノエン酸混合物３００ｇを使用して、これを日本薬局方１号ゼラチンカプセルに３００ｍｇずつ充填し、カプセルのキャップとボディーの接合部をゼラチンを用いてシールし、糖尿病予防治療用カプセル剤９００個を製造した。
得られたカプセル剤を、糖尿病の危険因子を有する社内ボランティアに１日当り１０個投与した結果、血糖値が顕著に改善された。
【００３４】
実施例２
ゴンドイン酸（シグマ社製）５００ｇ、エルカ酸（シグマ社製）１ｋｇ、及び無水エタノール（和光純薬工業社製）１．５ｋｇを混合し、均一溶媒とした。次いで、この混合溶液に炭酸カルシウム（和光純薬工業社製）８．５ｋｇを添加し、練り合わせ均一なものとしたものを４０℃で乾燥し、エタノールを除去する。
得られた組成物を打錠機（畑鉄鋼所社製）を使用して、３ｔ／ｍ2の圧力で直接打錠し、直径１０ｍｍ、重量４００ｍｇの錠剤を得た。
【００３５】
錠剤の表面を、フタル酸ヒドロキシプロピルメチルセルロース（信越化学社製）８．５ｋｇとアセトン（三井石油化学社製）１００ｋｇとの均一混合溶液で噴霧方式により被覆し、重量４４０ｍｇの糖尿病予防治療用錠剤３０，０００個を製造した。
得られた錠剤を、糖尿病の危険因子を有する社内ボランティアに１日当り３０個投与した結果、血糖値が顕著に改善された。
【００３６】
実施例３
からし油（美ノ久社製。ゴンドイン酸１４％、及びエルカ酸２１％を含有。）４．０ｋｇ及びソルビタン脂肪酸エステル（花王社製。ＨＬＢ３．８）２０ｇを添加し、均一に混合し、油相を形成した。油相をカゼインナトリウム［ニュージーランド・デイリー・ボード（New Zealand Dairy Board ）製］３．０ｋｇを溶解した水溶液９６ｋｇと混合し、該混合液をプロペラ攪拌機により７０℃で５分間予備乳化し、原料溶液約１００ｋｇを調製した。
【００３７】
次いで、該原料溶液を６０℃に加温して、ホモゲナイザー（三丸機械工業社製）で２段階均質化（１５ＭＰａ及び５ＭＰａ）し、超高温加熱殺菌機（森永乳業社製）を用いて、１３５℃で１５秒間殺菌処理し、糖尿病予防治療用合成乳約９０ｋｇを製造した。
得られた合成乳を、糖尿病の危険因子を有する社内ボランティアに１日当り２００ｍｌ給与した結果、血糖値が顕著に改善された。
【００３８】
実施例４
カゼイン［ニュージーランド・デイリー・ボード（New Zealand Dairy Board）製］４．２ｋｇ、デキストリン（参松工業社製。ＤＥ＝２７）１４．０ｋｇ、及び難消化性デキストリン（松谷化学工業社製）２．０ｋｇを水道水７５．３５ｋｇに分散し、溶解し、これに表３に示す配合量で混合されたミネラル混合物０．３ｋｇを添加して水相を形成した。水相に乳化剤としてグリセリン脂肪酸エステル（太陽化学社製）０．０３ｋｇを添加し、からし油（美ノ久社製。ゴンドイン酸１４％、及びエルカ酸２１％を含有。）４．０ｋｇと混合し、該混合液をプロペラ攪拌機により７０℃で５分間予備乳化し、原料溶液約１００ｋｇを調製した。
【００３９】
次いで、該原料溶液を高圧均質機［エイ・ピイ・ブイ・ラニエ（APV Rannie）社製］を使用し、３０ＭＰａの圧力で均質化処理した。均質化処理後、得られた乳化液に、表４に示す配合量で混合されたビタミン混合物０．０２ｋｇ及びバニラフレ−バ−（三栄源エフ・エフ・アイ社製）０．１ｋｇを添加し混合し、レトルトパウチ（東洋製罐社製）に２００ｍｌずつ充填し、密封し、栄養組成物入りレトルトパウチ４００個を製造した。該充填済レトルトパウチをレトルト殺菌機（日阪製作所社製）を使用して１２５℃で１０分間滅菌処理し、流動食としての糖尿病予防治療用栄養組成物４００個を製造した。
得られた流動食を、糖尿病の危険因子を有する社内ボランティアに使用した結果、血糖値が顕著に改善された。
【００４０】
【表３】
【表４】
【発明の効果】
以上詳記したとおり、本発明は、炭素数２０のモノエン酸及び／又はその誘導体、並びに炭素数２２のモノエン酸及び／又はその誘導体を有効成分とする糖尿病予防治療剤に関するものであり、本発明により奏せられる効果は次のとおりである。
本発明の糖尿病予防治療剤は、糖尿病を発症した患者の食餌療法等による治療、及び糖尿病の危険因子を有する者の糖尿病発症の予防に有用である。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a diabetes preventive / therapeutic agent for the purpose of treating a patient who has developed diabetes with diet therapy or the like, and preventing diabetes onset in a person having a risk factor for diabetes.
[0002]
More specifically, the present invention relates to a diabetes preventive and therapeutic agent containing a monoenoic acid having 20 carbon atoms and / or a derivative thereof, and a monoenoic acid having 22 carbon atoms and / or a derivative thereof as active ingredients.
[0003]
[Prior art]
Conventionally, it has been known that high oleic sunflower oil containing monounsaturated fatty acids (monoenoic acid) such as oleic acid is used as a fat source for nutritional compositions for patients with diabetes, a lifestyle-related disease. (JP-A-8-67630, hereinafter referred to as Prior Art 1).
However, these conventional techniques have the following disadvantages.
[0004]
[Problems to be solved by the invention]
As disclosed in the prior art, a nutritional composition for diabetic patients containing monoenoic acid has been developed. However, the prior art 1 does not disclose that monoenoic acid has an effect of preventing and treating diabetes. Furthermore, the nutritional composition for diabetic patients of the prior art 1 uses fats and oils mainly containing oleic acid having 18 carbon atoms as monoenoic acid, and carbon which is a higher monoenoic acid for the prevention and treatment of diabetes. The use of a combination of tens of monoenoic acids and / or their derivatives and monoenoic acids of 22 carbons and / or their derivatives, and the use of these in a specific weight ratio has never been studied.
[0005]
In view of the prior art, the present inventors have found a type of monoenoic acid and a combination thereof that are highly effective in preventing and treating diabetes, and have been testing various monoenoic acids for the purpose of developing a prophylactic and therapeutic agent for diabetes. went.
[0006]
As a result, the combination of the monoenoic acid having 20 carbon atoms and / or its derivative and the monoenoic acid having 22 carbon atoms and / or its derivative is compared with the conventional comparison, as is clear from the results of test examples described later. As a result, it was found that the effect of preventing and treating diabetes is higher than that in the case of using oils and fats mainly containing oleic acid having 18 carbon atoms, which is a monoenoic acid which is a low-grade monoenoic acid, and the present invention has been completed.
An object of the present invention is to provide a novel preventive and therapeutic agent for diabetes.
[0007]
[Means for Solving the Problems]
The present invention for solving the above-mentioned problems includes a monoenoic acid having 20 carbon atoms, a salt of a monoenoic acid having 20 carbon atoms and an alkali metal, an ester of a monoenoic acid having 20 carbon atoms and a lower aliphatic alcohol, and 20 carbon atoms. At least one selected from the group consisting of mono-, di-, and triglycerides of monoenoic acid, and a monoenoic acid having 22 carbon atoms, a salt of a monoenoic acid having 22 carbon atoms and an alkali metal, and a monoenoic acid having 22 carbon atoms A diabetic prophylactic and therapeutic agent comprising, as an active ingredient, at least one selected from the group consisting of an ester of a lower aliphatic alcohol and a mono-, di- or triglyceride of a monoenoic acid having 22 carbon atoms. and monoenoic acid, a salt of the monoenoic acid and alkali metal 20 carbon atoms, and esters of lower aliphatic alcohols and monoenoic acid 20 carbon atoms, charcoal Number 20 Mono monoenoic acid, against at least one 1 part by weight is selected from the group consisting of a di- or triglyceride, and monoenoic acids having 22 carbon atoms, and salts of monoenoic acid and an alkali metal having a carbon number of 22 A ratio of at least one selected from the group consisting of an ester of a monoenoic acid having 22 carbon atoms and a lower aliphatic alcohol and a mono-, di- or triglyceride of a monoenoic acid having 22 carbon atoms is 0.3 to 17 wt. Part (hereinafter referred to as aspect 1) is a desirable aspect.
[0008]
DETAILED DESCRIPTION OF THE INVENTION
Next, the present invention will be described in detail.
The monoenoic acid having 20 carbon atoms and / or its derivative, and the monoenoic acid having 22 carbon atoms and / or its derivative, which are active ingredients of the agent for preventing and treating diabetes of the present invention, specifically, gondoic acid having 20 carbon atoms ( (Gondoic acid), gadoleic acid, icosenoic acid (eicosenoic acid) such as 5-icosenoic acid and / or its derivatives, and erucic acid (erucic acid) having 22 carbon atoms, cetreic acid, docosenoic acid such as 5-docosenoic acid and / or Or a derivative thereof.
[0009]
The monoenoic acid having 20 carbon atoms and the monoenoic acid having 22 carbon atoms, which are higher monoenoic acids used in the present invention, are not particularly limited as long as they are pharmaceutically or food acceptable. Natural fats and oils, such as shark liver oil, whale oil, cod liver oil, rapeseed oil, mustard oil, cabbage seed oil, jojoba oil, meadowfoam oil, etc., can be used as they are or in appropriate combinations, It is also possible to extract and purify icosenoic acid or docosenoic acid from these natural fats and oils by conventional methods such as fractional distillation, crystallization, solvent extraction, urea inclusion, or chromatography. For convenience, commercially available gondoic acid or erucic acid (both manufactured by Sigma) can be used.
[0010]
The higher monoenoic acid used in the present invention is a monoenoic acid having 20 carbon atoms and a monoenoic acid derivative having 22 carbon atoms, so-called higher monoenoic acid derivatives, such as salts of higher monoenoic acid, various esters, etc. Includes derivatives. Specific examples thereof include salts with alkali metals such as sodium and potassium, esters with lower aliphatic alcohols such as methanol and ethanol, mono, di, and triglycerides.
[0011]
In addition, as shown in Aspect 1 of the present invention, 0.3 to 17 parts by weight of C22 monoenoic acid and / or its derivative is 1 part by weight of C20 monoenoic acid and / or its derivative. Compared to the case where the fat and oil contained in the ratio (hereinafter, sometimes referred to as a weight ratio in a specific range) as an active ingredient is not the weight ratio in the specific range, as is apparent from the results of test examples described later. Thus, it is desirable because it has a high effect of preventing and treating diabetes.
[0012]
The agent for preventing or treating diabetes according to the present invention can be administered to humans or animals by intravenous, oral, tube, or enteral administration, for example, depending on the administration method and therapeutic purpose. Various dosage forms that are forms of various pharmaceutical preparations can be selected. Representative examples thereof include tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, injections (solutions, suspensions, etc.) and the like.
[0013]
Moreover, the diabetes preventive treatment agent of this invention can be ingested as a nutritional composition which is a form of common food-drinks for the use for diet therapy.
[0014]
In the case of oral administration (the same applies to diet therapy), the effective dose of the agent for preventing and treating diabetes of the present invention is as follows. From the results of the test using mice, the monoene acid having 20 carbon atoms and / or its derivatives, and the monoene having 22 carbon atoms. It was found to be 5 to 400 mg / kg body weight / day based on the amount of the active ingredient comprising an acid and / or a derivative thereof (hereinafter sometimes referred to as higher monoenoic acids).
[0015]
In addition, the higher monoenoic acids that are the active ingredients of the diabetes preventive and therapeutic agent of the present invention have extremely low toxicity as a result of an acute toxicity test by oral administration using mice, and the LD 50 is 10 g / kg body weight or more. It can be used safely for animals and with very few side effects.
[0016]
Furthermore, the preventive / therapeutic agent for diabetes of the present invention can be used in combination with other substances having a preventive and therapeutic effect for diabetes such as monoenoic acid and polyunsaturated fatty acid. In particular, it is desirable to contain a monoenoic acid having 24 carbon atoms and / or a derivative thereof from the viewpoint of synergistically increasing the preventive and therapeutic effects of diabetes.
[0017]
The content of the monoenoic acid having 24 carbon atoms and / or the derivative thereof is the number of carbon atoms relative to 1 part by weight of the monoenoic acid having 20 carbon atoms and / or its derivative in the diabetes preventive / therapeutic agent of aspect 1 of the present invention. The inclusion of 24 monoenoic acids and / or derivatives thereof in a weight ratio of 0.1 to 10 parts by weight is desirable because the effect of preventing and treating diabetes is synergistically enhanced. That is, 0.3 to 17 parts by weight of a monoenoic acid having 22 carbons and / or a derivative thereof, and a monoenoic acid having 24 carbons and / or 1 part by weight of a monoenoic acid having 20 carbons and / or a derivative thereof. A diabetic preventive / therapeutic agent containing as an active ingredient an oil containing 0.1 to 10 parts by weight of the derivative is desirable because it further enhances the preventive and therapeutic effects of diabetes.
[0018]
The monoenoic acid having 24 carbon atoms and / or its derivative is specifically tetracosenoic acid such as nervonic acid having 24 carbon atoms (ceracoleic acid, succinic acid) and / or its derivative.
[0019]
Next, the present invention will be described in detail with reference to test examples.
Test example 1
This test was conducted to compare the prior art with the present invention using blood glucose level as an index.
(1) Preparation of sample A commercially available feed for mice (CRF-1, manufactured by Oriental Yeast Co., Ltd.) is 1% of the components shown in the following test samples (weight, hereinafter the same unless otherwise specified). 12 types of samples were prepared.
Sample 1: Higher monoenoic acid mixture composed of 1 part by weight of gondoic acid, which is a monoenoic acid having 20 carbon atoms of the present invention, and 1 part by weight of erucic acid, which is a monoenoic acid having 22 carbon atoms. Sample 2: Gondoic acid sample 3: Sample of erucic acid 4: C18 oleic acid sample 5: monoenoic acid mixture sample consisting of 1 part by weight of oleic acid and 1 part by weight of erucic acid sample 6: monoenoic acid mixture sample consisting of 1 part by weight of oleic acid and 1 part by weight of gondoic acid 7: conventional Technology 1 olive oil sample 8: Prior art 1 canola oil sample 9: Prior art 1 high oleic safflower oil sample 10: Prior art 1 high oleic sunflower oil sample 11: Prior art 1 soybean oil sample 12: As a control Lard Gondoic acid, erucic acid, and oleic acid were all commercially available products (manufactured by Sigma). Also, olive oil, canola oil, high olein safflower oil, high olein sunflower oil, and soybean oil were all commercially available products (Nisshin Oil Industries). Furthermore, lard used a commercial item (Taiyo Yushi Co., Ltd.).
[0020]
(2) Test method C57BL / KsJ-db / db mouse (8-week-old male, which is known to exhibit hyperglycemia due to overeating due to abnormal appetite as a diabetes model animal, hereinafter referred to as db mouse. (Available from Charles River Japan, Inc.) was used for each test group.
[0021]
Each mouse in each test group was allowed to freely ingest the above 12 kinds of samples and water, raised for 4 weeks, that is, up to 12 weeks of age, and then collected blood and measured blood glucose level by the following method. (8 weeks old) and the control group of sample 12 were evaluated and tested for the prevention and treatment effects of diabetes.
The blood glucose level was measured using a commercially available Glutest sensor (manufactured by Sanwa Chemical Laboratories) after collecting a small amount of blood from the tail vein of the mouse using a syringe for injection.
[0022]
(3) Test results The results of this test are as shown in Table 1. As is clear from Table 1, the higher monoenoic acid mixture sample 1 of the present invention is a control group using a blood glucose level (460 mg / dl) at the start of the test (8 weeks old) and lard (manufactured by Taiyo Oil & Fats Co., Ltd.) as the test sample. A significant decrease in blood glucose level was observed as compared with the blood glucose level of (Sample 12), that is, diabetes prevention and treatment effects were observed.
[0023]
Further, the higher monoenoic acid mixture sample 1 of the present invention is olive oil, canola oil, high oleic safflower oil, high oleic sunflower oil, or oils mainly containing oleic acid having 18 carbon atoms as the monoenoic acid of Prior Art 1. Compared to Samples 7 to 11 using soybean oil, it was confirmed that the blood glucose level was excellent, that is, the diabetes prevention and treatment effect was excellent.
[0024]
Furthermore, the higher monoenoic acid mixture sample 1 of the present invention has a blood glucose level lowering action as compared with the sample 2 using gondoic acid alone, the sample 3 using erucic acid alone, and the sample 4 using oleic acid alone. Compared with Sample 5 which is a monoenoic acid mixture obtained by substituting gonoic acid of sample 1 with oleic acid and Sample 6 which is a monoenoic acid mixture obtained by substituting erucic acid with sample oleic acid. Because of its excellent value-lowering action, for the prevention and treatment of diabetes, it is possible to use a combination of gondoic acid which is a monoenoic acid having 20 carbon atoms and erucic acid which is a monoenoic acid having 22 carbon atoms, that is, It has been found that it is effective to use a monoenoic acid having 20 carbon atoms and / or a derivative thereof and a monoenoic acid having 22 carbon atoms and / or a derivative thereof in combination.
[0025]
Note that gadolinic acid, 5-icosenoic acid, or a derivative thereof having 20 carbon atoms in place of gondonic acid, or cetoleic acid, 5-docosenoic acid having 22 carbon atoms, or a derivative thereof in place of erucic acid. Although tested, almost similar results were obtained. Further, the weight ratio of the monoenoic acid in Sample 1 was appropriately changed within the range of 0.3 to 17 parts by weight of erucic acid with respect to 1 part by weight of gondonic acid, and almost the same result was obtained. Further, the weight ratio of the monoenoic acid in Sample 5 and Sample 6 was changed as appropriate for testing, and almost the same result was obtained.
[0026]
[Table 1]
Test example 2
This test was performed in order to examine the weight ratio of monoenoic acid having 20 carbon atoms and / or its derivative and monoenoic acid having 22 carbon atoms and / or its derivative, using blood glucose level as an index.
(1) Preparation of samples The following four types of samples were prepared by the same method as in Test Example 1.
Sample 13: A higher monoenoic acid mixture composed of 1 part by weight of gonoic acid, which is a monoenoic acid having 20 carbon atoms, and 0.2 part by weight of erucic acid, which is a monoenoic acid having 22 carbon atoms. Sample 14: Gondoin, which is a monoenoic acid having 20 carbon atoms. Higher monoenoic acid mixture sample 1 consisting of 1 part by weight of acid and 0.3 part by weight of erucic acid which is a monoenoic acid having 22 carbon atoms Sample 15: 1 part by weight of gondoic acid which is a monoenoic acid having 20 carbon atoms and monoenoic acid having 22 carbon atoms Higher monoenoic acid mixture sample consisting of 17 parts by weight of erucic acid Sample 16: higher monoenoic acid mixture consisting of 1 part by weight of gondoic acid which is a monoenoic acid having 20 carbon atoms and 18 parts by weight of erucic acid which is a monoenoic acid having 22 carbon atoms ]
(2) Test Method Each sample was tested for the effect of preventing and treating diabetes by the test method of Test Example 1.
[0029]
(3) Test results The results of this test are as shown in Table 2. As is apparent from Table 2, when erucic acid, which is a monoenoic acid having 22 carbon atoms, is in a weight ratio of 0.3 to 17 parts by weight with respect to 1 part by weight of gonoic acid, which is a monoenoic acid having 20 carbon atoms, In order to prevent and treat diabetes more effectively because of its superior blood glucose level-lowering action, C22 monoene acid and / or C20 monoenoic acid and / or 1 part by weight of its derivatives It has been found that the ratio of the derivative is preferably in the range of 0.3 to 17 parts by weight.
[0030]
Note that gadolinic acid, 5-icosenoic acid, or a derivative thereof having 20 carbon atoms in place of gondonic acid, or cetoleic acid, 5-docosenoic acid having 22 carbon atoms, or a derivative thereof in place of erucic acid. Although tested, almost similar results were obtained.
[0031]
[Table 2]
EXAMPLES Next, although an Example is shown and this invention is demonstrated further in detail, this invention is not limited to a following example.
[0033]
【Example】
Example 1
Using 300 g of a higher monoenoic acid mixture of 150 g of gondoic acid (manufactured by Sigma) and 150 g of erucic acid (manufactured by Sigma), 300 mg each of this mixture was filled into a Japanese Pharmacopoeia No. 1 gelatin capsule to join the cap and body of the capsule The part was sealed with gelatin to prepare 900 capsules for the prevention and treatment of diabetes.
As a result of administering 10 capsules obtained per day to in-house volunteers having a risk factor for diabetes, blood glucose level was remarkably improved.
[0034]
Example 2
500 g of gondoic acid (manufactured by Sigma), 1 kg of erucic acid (manufactured by Sigma), and 1.5 kg of absolute ethanol (manufactured by Wako Pure Chemical Industries, Ltd.) were mixed to obtain a uniform solvent. Next, 8.5 kg of calcium carbonate (manufactured by Wako Pure Chemical Industries, Ltd.) is added to this mixed solution, and the mixture is kneaded and dried at 40 ° C. to remove ethanol.
The obtained composition was directly tableted using a tableting machine (manufactured by Hata Steel Co., Ltd.) at a pressure of 3 t / m 2 to obtain a tablet having a diameter of 10 mm and a weight of 400 mg.
[0035]
The tablet surface was coated with a uniform mixed solution of 8.5 kg of hydroxypropylmethylcellulose phthalate (manufactured by Shin-Etsu Chemical Co., Ltd.) and 100 kg of acetone (manufactured by Mitsui Petrochemical Co., Ltd.) by spraying, and the tablet 30 for diabetes prevention and treatment having a weight of 440 mg. 1,000 pieces were produced.
As a result of administering 30 of the obtained tablets to in-house volunteers having a risk factor for diabetes per day, blood glucose level was remarkably improved.
[0036]
Example 3
Mustard oil (Minohisa, Inc. containing 14% gondonic acid and 21% erucic acid) and 4.0 g of sorbitan fatty acid ester (Kao Co., Ltd., HLB3.8) were added and mixed uniformly. An oil phase formed. The oil phase was mixed with 96 kg of an aqueous solution in which 3.0 kg of sodium caseinate [manufactured by New Zealand Dairy Board] was dissolved, and the mixture was pre-emulsified with a propeller stirrer at 70 ° C. for 5 minutes, 100 kg was prepared.
[0037]
Next, the raw material solution is heated to 60 ° C., homogenized (manufactured by Sanmaru Kikai Kogyo Co., Ltd.) in two stages and homogenized (15 MPa and 5 MPa), using an ultra-high temperature heat sterilizer (manufactured by Morinaga Milk Industry Co., Ltd.) Sterilized at 135 ° C. for 15 seconds to produce about 90 kg of synthetic milk for diabetes prevention and treatment.
As a result of feeding 200 ml of the obtained synthetic milk to an in-house volunteer having a risk factor for diabetes per day, the blood glucose level was remarkably improved.
[0038]
Example 4
Casein [New Zealand Dairy Board] 4.2 kg, dextrin (Sanmatsu Kogyo Co., DE = 27) 14.0 kg, and indigestible dextrin (Matsutani Chemical Co., Ltd.) 2.0 kg Was dispersed and dissolved in 75.35 kg of tap water, and 0.3 kg of a mineral mixture mixed in the blending amounts shown in Table 3 was added thereto to form an aqueous phase. 0.03 kg of glycerin fatty acid ester (manufactured by Taiyo Chemical Co., Ltd.) is added to the aqueous phase as an emulsifier, and mixed with 4.0 kg of mustard oil (manufactured by Minohisa Co., Ltd., containing 14% gondoic acid and 21% erucic acid). The mixed solution was pre-emulsified with a propeller stirrer at 70 ° C. for 5 minutes to prepare about 100 kg of a raw material solution.
[0039]
Next, the raw material solution was homogenized at a pressure of 30 MPa using a high-pressure homogenizer (manufactured by APV Rannie). After the homogenization treatment, 0.02 kg of vitamin mixture and 0.1 kg of vanilla flavor (manufactured by San-Ei Gen FFI Co., Ltd.) mixed in the blending amounts shown in Table 4 were added to the obtained emulsion and mixed. Then, 200 ml each of retort pouches (manufactured by Toyo Seikan Co., Ltd.) were filled and sealed to produce 400 retort pouches containing a nutritional composition. The filled retort pouch was sterilized at 125 ° C. for 10 minutes using a retort sterilizer (manufactured by Nisaka Manufacturing Co., Ltd.) to produce 400 nutritional compositions for diabetes prevention and treatment as a liquid food.
As a result of using the obtained liquid food for in-house volunteers with risk factors for diabetes, blood glucose level was remarkably improved.
[0040]
[Table 3]
[Table 4]
【The invention's effect】
As described above in detail, the present invention relates to a monoenoic acid having 20 carbon atoms and / or a derivative thereof, and a preventive / therapeutic agent for diabetes comprising a monoenoic acid having 22 carbon atoms and / or a derivative thereof as an active ingredient. The effects produced by are as follows.
The agent for preventing or treating diabetes according to the present invention is useful for treating a patient who has developed diabetes with diet therapy or the like and for preventing the onset of diabetes in those who have risk factors for diabetes.
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001000320A JP4707839B2 (en) | 2000-02-07 | 2001-01-05 | Diabetes prevention and treatment |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000028641 | 2000-02-07 | ||
| JP2000-28641 | 2000-02-07 | ||
| JP2000028641 | 2000-02-07 | ||
| JP2001000320A JP4707839B2 (en) | 2000-02-07 | 2001-01-05 | Diabetes prevention and treatment |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2001294525A JP2001294525A (en) | 2001-10-23 |
| JP4707839B2 true JP4707839B2 (en) | 2011-06-22 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001000320A Expired - Lifetime JP4707839B2 (en) | 2000-02-07 | 2001-01-05 | Diabetes prevention and treatment |
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| Country | Link |
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| JP (1) | JP4707839B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003532311A (en) * | 2000-03-05 | 2003-10-28 | イトラン コミュニケーションズ リミテッド | Spread spectrum communication system using differential code shift keying |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE462723T1 (en) * | 2004-03-01 | 2010-04-15 | Pharmafrontier Co Ltd | PHARMACEUTICAL COMPOSITION FOR LOWERING BLOOD SUGAR LEVELS |
| JP5970450B2 (en) * | 2011-03-04 | 2016-08-17 | 日本水産株式会社 | Metabolic syndrome improver |
| AU2015285212A1 (en) * | 2014-07-02 | 2017-01-12 | Nippon Suisan Kaisha, Ltd | Production method of marine product-derived free monounsaturated fatty acids or lower alcohol esters thereof |
-
2001
- 2001-01-05 JP JP2001000320A patent/JP4707839B2/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003532311A (en) * | 2000-03-05 | 2003-10-28 | イトラン コミュニケーションズ リミテッド | Spread spectrum communication system using differential code shift keying |
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| Publication number | Publication date |
|---|---|
| JP2001294525A (en) | 2001-10-23 |
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