JP2016502539A - 心臓疾患の予防又は治療用組成物 - Google Patents
心臓疾患の予防又は治療用組成物 Download PDFInfo
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- JP2016502539A JP2016502539A JP2015545368A JP2015545368A JP2016502539A JP 2016502539 A JP2016502539 A JP 2016502539A JP 2015545368 A JP2015545368 A JP 2015545368A JP 2015545368 A JP2015545368 A JP 2015545368A JP 2016502539 A JP2016502539 A JP 2016502539A
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
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- 235000010355 mannitol Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
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- 229920000609 methyl cellulose Polymers 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229940111688 monobasic potassium phosphate Drugs 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000003680 myocardial damage Effects 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
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- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229940020573 plavix Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000001107 psychogenic effect Effects 0.000 description 1
- 230000010349 pulsation Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
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- 230000003938 response to stress Effects 0.000 description 1
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- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 description 1
- 235000019173 retinyl acetate Nutrition 0.000 description 1
- 239000011770 retinyl acetate Substances 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
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- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
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- 229960003080 taurine Drugs 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
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- 230000002792 vascular Effects 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
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- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
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Abstract
Description
本発明は、他の観点において、対象に前記一般式1で示される化合物、その誘導体又は薬学的に許容し得るその塩を有効量投与し、心臓疾患を予防又は治療する方法に関するものである。
(-)-シリンガレシノールを合成する段階を示すと、次の反応式のとおりである。
窒素雰囲気でシリンガアルデヒド(syringaldehyde)(化合物1)(3g、16.47mmol)と炭酸カリウム(6.83g、49.4mmol)をDMF(16mL)に溶かした後、臭化ベンジル(2.94mL、24.7mmol)を入れ、室温で一晩中攪拌する。TLCで反応終結を確認した後、反応溶液を水とエチルアセテートで抽出する。抽出した有機層を水で3回洗浄し、無水MgSO4で脱水してからフィルターでろ過する。ろ過液を濃縮し、カラムクロマトグラフィー(5:1ヘキサン/EtOAc)で精製して白色固体の化合物20(4.45g、99.2%)を収得した。化合物2のNMRデータは、下記のとおりである。
窒素雰囲気で前記収得した化合物2(4.04g、14.8mmol)を無水THF(30mL)に溶かした後、−78℃に温度を下げる。臭化ビニルマグネシウム(17.8mLの1M THF溶液)を入れ、−78℃で10分間攪拌した後、0℃に温度を上げて、再び2時間攪拌する。TLCで反応終結を確認した後、反応溶液を飽和NH4Cl水溶液でクエンチングし(quenching)、エチルアセテートで抽出する。抽出した有機層を水で3回洗浄し、無水MgSO4で脱水してからフィルターでろ過する。ろ過液を濃縮し、カラムクロマトグラフィー(4:1ヘキサン/EtOAc)で精製して薄い黄色固体の化合物21(3.97g、89.1%)を収得した。化合物3のNMRデータは下記のとおりである。
窒素雰囲気でdried powdered 4Åモレキュラーシーブ(molecular sieve)(10.5g)に無水塩化メチレン(45mL)を入れ、−20℃に温度を下げる。これに(+)-DIPT(diisopropyltryptamine)(1.18mL、5.99mmol)を入れた後、チタンイソプロポキシド(titanium isopropoxide)(1.48mL、4.99mmol)をゆっくり入れて30分間攪拌する。30分後、クメンヒドロキシド(cumene hydroxide)(1.85mL、80%、5.99mmol)を入れて30分間攪拌する。次いで、無水塩化メチレン(10mL)に溶かした化合物3(3g、9.99mmol)をゆっくり一滴ずつ添加(dropwise addition)する。−20℃で5時間攪拌した後、0℃に温度を上げて一晩中攪拌する。TLCで反応を確認した後、10%NaOH溶液(30mL、in飽和NaCl溶液)を入れて3時間攪拌した後、フィルターでろ過する。ろ過液を塩化メチレンで抽出し、ブライン(brine)溶液で洗浄する。無水Na2SO4で脱水し、フィルターでろ過した後、該ろ過液を濃縮し、カラムクロマトグラフィー(3:1ヘキサン/EtOAc)で精製して化合物4(1.65g、55.0%、赤色オイル)および化合物5(1.06g、33.5%、赤色オイル)を収得した。化合物5のNMRデータは下記のとおりである。
窒素雰囲気で活性亜鉛粉(activated zinc dust)(0.146g、4.44mmol)が入っているフラスコにTHF(20mL)に溶かしたCp2TiCl2(0.182g、1.463mmol)を入れ、化合物7(0.19g、0.635mmol)をTHF(16mL)に溶かしてから、60℃に合わせた後、先に製造したCp2TiCl溶液をカニューレ(cannula)にて20分間加える。20分間攪拌した後、THF(4mL)に溶かしたI2(0.105g、0.825mmol)を付加し、反応溶液を1時間攪拌する。TLCで反応終結を確認した後、反応溶液に飽和NH4Cl水溶液を入れて反応を終結させ、ジエチルエーテルで抽出する。抽出した有機層を3回10% Na2S2O3溶液およびブライン溶液で洗浄し、無水Na2SO4で脱水してから、フィルターでろ過する。ろ過液を濃縮し、カラムクロマトグラフィー(3:1ヘキサン/EtOAc)で精製して薄い赤色オイルの化合物8(62mg、32.6%)を収得した。化合物8のNMRデータは下記のとおりである。
化合物8(90mg、0.152mmol)をエタノール/THF(1:1)(9mL)に溶かした後、温度を65℃に合わせる。これにラネーニッケル(Raney nickel)(0.15g)を入れ、65℃で1時間攪拌する。TLCで反応終結を確認した後、反応溶液をアセトンとセライト(celite)を用いてろ過してから、ろ過液を濃縮し、カラムクロマトグラフィー(1:1ヘキサン/EtOAc)で精製して薄い黄色固体の化合物(50mg、78.7%)を収得した。収得した化合物が(8S、8'S)-(-)-シリンガレシノールであることは、下記のようなNMRデータおよび[α]D値が−38.5°(c 0.1,CHCl3)であることから確認できる。
(+)-シリンガレシノールを合成する段階を示すと、次の反応式のとおりである。
比較例の化合物5を製造する方法に比べて、(+)-DIPTの代わりに(-)-DIPTを用いることを除いては、実質的に同法によって化合物3〜化合物10を製造した。化合物10のNMRデータは下記のとおりである。
比較例の化合物7を製造する方法と実質的に同法によって化合物6と化合物10とを反応させて化合物11を収得した。化合物11のNMRデータは下記のとおりである。
比較例の化合物8を製造する方法と実質的に同法によって化合物11から化合物12を収得した。化合物12のNMRデータは下記のとおりである。
1H NMR (300 MHz, CDCl3) δ3.11 (m, 2H), 3.84 (s, 12H), 3.93 (dd, J = 9.4, 3.6 Hz, 2H), 4.31 (dd, J= 9.3, 7.2 Hz, 2H), 4.75 (d, J = 3.9 Hz, 2H), 4.99 (s, 4H), 6.57 (s, 4H), 7.28-7.51 (m, 10H); 13C NMR (75 MHz, CDCl3) δ54.3, 56.2, 72.0, 75.0, 86.0, 103.0, 127.8, 128.1, 128.4, 136.8, 137.8, 153.7.
比較例の(-)-シリンガレシノールを製造する方法と実質的に同法によって化合物12から(+)-シリンガレシノールを製造した。製造した化合物が(8R、8'R)-(+)-シリンガレシノールであることは、下記のようなNMRデータおよび[α]D値が+40.9°(c 0.1,CHCl3)であることから確認できる。
一方、化合物6(臭化シンナミル)は、シリンガアルデヒド(1)の化合物2をHorner−Wadsworth−Emmonsオレフィン化させて不飽和エステル基を有する化合物(13)にした後、DIBAL−Hで還元させて不飽和アルコール基を有する化合物(14)にし、再びPBr3にてOHをBrに置換させて製造することができる。具体的な化学反応式は下記を参考する。
二種のシリンガレシノールの光学異性体に対し、マウスの心筋細胞でのSIRT 1遺伝子発現促進効果を評価するために、下記のような実験を行なった。
実験例1と実質的に同法によって分離、培養した心筋細胞を、血清を除去した培地で250mM濃度の過酸化水素水(H2O2)にて2時間処理して活性酸素による細胞死滅を誘導した。2時間後、培地を除去し、PBSで洗浄してから5,20,50mM濃度の(+)-シリンガレシノールと(-)-シリンガレシノールを24時間処理した。各細胞に3−[4,5−ジメチル−2−チアゾリル]−2,5−ジフェニルテトラゾリウムブロミド(MTT、Sigma)溶液を入れ、37℃で4時間培養し、これにジメチルスルホキシドを入れて溶かした後、ELISAリーダー(サーモマックス、モレキュラーデバイス社製)を利用して540nmの波長で形成されたホルマザンダイの光学的濃度(OD)を測定した結果、図3を得た。図3は、過酸化水素水(H2O2)を処理した心筋細胞に(+)-シリンガレシノール[syn(+)]または(-)-シリンガレシノール[syn(-)]を処理し、ELISAリーダー(サーモマックス、モレキュラーデバイス社製)を利用して540nmの波長で形成されたホルマザンダイの光学的濃度(OD)を測定した結果である。
1.エゾウコギの前処理
エゾウコギを収獲し、その皮をむいてエゾウコギ皮を製造した。
製造されたエゾウコギ皮5gにメタノール3mLを加えてエゾウコギ抽出物1ml(エゾウコギM)を得た。これに対してエチルアセテートを処理して分離した後(エゾウコギM-e)、HPLCで分析した。前記分離・精製方法を図式化して図4に示し、HPLC結果を図5に示した。
試料をメタノールに溶かし、超臨界流体クロマトグラフィー(SFC:Supercritical fluid chromatography)法を用いてキラルカラム(chiral column, Chiralpak IB column)にて分離し、UV210nmで検出した。
1.ジンセンベリー(高麗人参の実)の前処理
生ジンセンベリーを収獲し、種子を分離して除去した後、ジンセンベリーの果皮を除去し果肉だけを日光乾燥または熱風乾燥して高麗人参実果肉乾燥物を製造した。
前記製造したジンセンベリー果肉乾燥物1kgに水又はアルコール3Lを加えて室温又は還流抽出し、ろ過した後、40〜45℃で減圧濃縮してジンセンベリー果肉抽出物300gを得た。抽出物にエーテルを処理して脂溶性成分を除去した後、ブタノールで粗サポニンを抽出および濃縮した。これを分離・精製してシリンガレシノールを得、その具体的な方法は次のとおりである。
試料をメタノールに溶かし、超臨界流体クロマトグラフィー(SFC:Supercritical fluid chromatography)法を用いてキラルカラム(Chiralpak IB column)にて分離し、UV210nmで検出した。
(+)-シリンガレシノール................... 1000mg
ビタミン混合物
ビタミンAアセテート....................... 70μg
ビタミンe................................. 1.0mg
ビタミンB1............................... 0.13mg
ビタミンB2............................... 0.15mg
ビタミンB6............................... 0.5mg
ビタミンB12............................. 0.2μg
ビタミンC................................. 10mg
ビオチン................................... 10μg
ニコチン酸アミド........................... 1.7mg
葉酸....................................... 50μg
パントテン酸カルシウム..................... 0.5mg
無機質混合物
硫酸第一鉄................................. 1.75mg
酸化亜鉛................................... 0.82mg
炭酸マグネシウム........................... 25.3mg
第一リン酸カリウム......................... 15mg
第二リン酸カルシウム....................... 55mg
クエン酸カリウム........................... 90mg
炭酸カルシウム............................. 100mg
塩化マグネシウム........................... 24.8mg
(+)-シリンガレシノール................... 1000mg
クエン酸................................... 1000mg
オリゴ糖................................... 100g
タウリン................................... 1g
精製水..................................... 残量
(+)-シリンガレシノール100mg、大豆抽出物50mg、葡萄糖100mg、紅参抽出物50mg、澱粉96mg、およびマグネシウムステアレート4mgを混合し、30%エタノールを40mg添加して顆粒を形成した後、60℃で乾燥し、打錠機を利用して打錠して得る。
(+)-シリンガレシノール100mg、大豆抽出物50mg、葡萄糖100mg、および澱粉600mgを混合し、30%エタノールを100mg添加して顆粒を形成した後、60℃で乾燥して顆粒を形成し、それを包みに充填して得る。
下記の表1に表した組成により通常の方法にて軟膏を製造した。
窒素雰囲気でシリンガアルデヒド(syringaldehyde)(化合物1)(3g、16.47mmol)と炭酸カリウム(6.83g、49.4mmol)をDMF(16mL)に溶かした後、臭化ベンジル(2.94mL、24.7mmol)を入れ、室温で一晩中攪拌する。TLCで反応終結を確認した後、反応溶液を水とエチルアセテートで抽出する。抽出した有機層を水で3回洗浄し、無水MgSO4で脱水してからフィルターでろ過する。ろ過液を濃縮し、カラムクロマトグラフィー(5:1ヘキサン/EtOAc)で精製して白色固体の化合物2(4.45g、99.2%)を収得した。化合物2のNMRデータは、下記のとおりである。
窒素雰囲気で前記収得した化合物2(4.04g、14.8mmol)を無水THF(30mL)に溶かした後、−78℃に温度を下げる。臭化ビニルマグネシウム(17.8mLの1M THF溶液)を入れ、−78℃で10分間攪拌した後、0℃に温度を上げて、再び2時間攪拌する。TLCで反応終結を確認した後、反応溶液を飽和NH4Cl水溶液でクエンチングし(quenching)、エチルアセテートで抽出する。抽出した有機層を水で3回洗浄し、無水MgSO4で脱水してからフィルターでろ過する。ろ過液を濃縮し、カラムクロマトグラフィー(4:1ヘキサン/EtOAc)で精製して薄い黄色固体の化合物3(3.97g、89.1%)を収得した。化合物3のNMRデータは下記のとおりである。
窒素雰囲気でdried powdered 4Åモレキュラーシーブ(molecular sieve)(10.5g)に無水塩化メチレン(45mL)を入れ、−20℃に温度を下げる。これに(+)-DIPT(diisopropyltryptamine)(1.18mL、5.99mmol)を入れた後、チタンイソプロポキシド(titanium isopropoxide)(1.48mL、4.99mmol)をゆっくり入れて30分間攪拌する。30分後、クメンヒドロペルオキシド(cumene hydroperoxide)(1.85mL、80%、5.99mmol)を入れて30分間攪拌する。次いで、無水塩化メチレン(10mL)に溶かした化合物3(3g、9.99mmol)をゆっくり一滴ずつ添加(dropwise addition)する。−20℃で5時間攪拌した後、0℃に温度を上げて一晩中攪拌する。TLCで反応を確認した後、10%NaOH溶液(30mL、in飽和NaCl溶液)を入れて3時間攪拌した後、フィルターでろ過する。ろ過液を塩化メチレンで抽出し、ブライン(brine)溶液で洗浄する。無水Na2SO4で脱水し、フィルターでろ過した後、該ろ過液を濃縮し、カラムクロマトグラフィー(3:1ヘキサン/EtOAc)で精製して化合物4(1.65g、55.0%、赤色オイル)および化合物5(1.06g、33.5%、赤色オイル)を収得した。化合物5のNMRデータは下記のとおりである。
Claims (10)
- 下記の一般式1で示される化合物、その誘導体又は薬学的に許容し得るその塩を有効成分として含む心臓疾患の予防又は治療用組成物。
- 前記化合物は(+)-シリンガレシノールである、請求項1に記載の心臓疾患の予防又は治療用組成物。
- 前記心臓疾患は心血管疾患である、請求項1に記載の心臓疾患の予防又は治療用組成物。
- 前記心血管疾患は、脳梗塞、脳出血、高血圧、虚血性心疾患、心筋梗塞、心不全、および動脈硬化からなる群より選ばれた一つ以上を含む、請求項3に記載の心臓疾患の予防又は治療用組成物。
- 前記組成物は、該組成物の総重量を基準に0.001重量%〜80重量%の(+)-シリンガレシノールを含む、請求項1に記載の心臓疾患の予防又は治療用組成物。
- 前記有効成分はSIRT(SIRTuin) 1の発現を促進する、請求項1に記載の心臓疾患の予防又は治療用組成物。
- 前記有効成分は心筋細胞の死滅を抑制する、請求項1に記載の心臓疾患の予防又は治療用組成物。
- 前記組成物は(-)-シリンガレシノールをさらに含み、
(+)-シリンガレシノールの重量が(-)-シリンガレシノールの重量の2倍以上である、請求項1に記載の心臓疾患の予防又は治療用組成物。 - 前記組成物は食品組成物である、請求項1乃至8のいずれか1項に記載の心臓疾患の予防又は治療用組成物。
- 前記組成物は薬学組成物である、請求項1乃至8のいずれか1項に記載の心臓疾患の予防又は治療用組成物。
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Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6330416A (ja) * | 1986-07-24 | 1988-02-09 | Wakunaga Pharmaceut Co Ltd | 脳循環代謝改善剤 |
JPH08268887A (ja) * | 1995-02-01 | 1996-10-15 | Suntory Ltd | 高血圧症又はそれに起因する医学的症状の予防又は改善剤 |
JP2004352652A (ja) * | 2003-05-29 | 2004-12-16 | Minabegawamura | ヘリコバクターピロリの運動能阻害剤 |
JP2007302644A (ja) * | 2006-05-08 | 2007-11-22 | Rooman Kogyo:Kk | Ap−1モチーフを介する遺伝子発現抑制剤 |
JP2009263359A (ja) * | 2008-03-31 | 2009-11-12 | Shiseido Co Ltd | 血管の成熟化・正常化・安定化剤 |
JP2010528108A (ja) * | 2007-05-28 | 2010-08-19 | アモーレパシフィック コーポレイション | 高麗人参の実抽出物を含有する血行促進、血管新生促進及び虚血性心疾患治療用、皮膚美容増進用並びに男性性機能改善用組成物 |
JP2011509996A (ja) * | 2008-01-18 | 2011-03-31 | ヤン ジ ケミカル カンパニー リミテッド | ダンコウバイ抽出物を含む心血管系疾患の予防および治療用の組成物 |
WO2012141876A1 (en) * | 2011-04-15 | 2012-10-18 | Nestec S.A. | Methods for regulating sirtuin gene expression |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030144216A1 (en) * | 2002-01-25 | 2003-07-31 | Mikko Unkila | Method for prevention of diseases in coeliac patients |
KR20040033983A (ko) * | 2002-10-16 | 2004-04-28 | 학교법인 상지학원 | 항염증 및 항침해수용 활성을 갖는 리리오덴드린을 함유한가시오가피 수피의 추출물 및 이를 함유하는 조성물 |
KR20040050396A (ko) | 2002-12-10 | 2004-06-16 | 한국식품개발연구원 | 천궁을 이용한 일산화질소 생성제 조성물 및 이를 이용한약품 조성물 |
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Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6330416A (ja) * | 1986-07-24 | 1988-02-09 | Wakunaga Pharmaceut Co Ltd | 脳循環代謝改善剤 |
JPH08268887A (ja) * | 1995-02-01 | 1996-10-15 | Suntory Ltd | 高血圧症又はそれに起因する医学的症状の予防又は改善剤 |
JP2004352652A (ja) * | 2003-05-29 | 2004-12-16 | Minabegawamura | ヘリコバクターピロリの運動能阻害剤 |
JP2007302644A (ja) * | 2006-05-08 | 2007-11-22 | Rooman Kogyo:Kk | Ap−1モチーフを介する遺伝子発現抑制剤 |
JP2010528108A (ja) * | 2007-05-28 | 2010-08-19 | アモーレパシフィック コーポレイション | 高麗人参の実抽出物を含有する血行促進、血管新生促進及び虚血性心疾患治療用、皮膚美容増進用並びに男性性機能改善用組成物 |
JP2011509996A (ja) * | 2008-01-18 | 2011-03-31 | ヤン ジ ケミカル カンパニー リミテッド | ダンコウバイ抽出物を含む心血管系疾患の予防および治療用の組成物 |
JP2009263359A (ja) * | 2008-03-31 | 2009-11-12 | Shiseido Co Ltd | 血管の成熟化・正常化・安定化剤 |
WO2012141876A1 (en) * | 2011-04-15 | 2012-10-18 | Nestec S.A. | Methods for regulating sirtuin gene expression |
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Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20171205 |