JPH0516413B2 - - Google Patents
Info
- Publication number
- JPH0516413B2 JPH0516413B2 JP60011679A JP1167985A JPH0516413B2 JP H0516413 B2 JPH0516413 B2 JP H0516413B2 JP 60011679 A JP60011679 A JP 60011679A JP 1167985 A JP1167985 A JP 1167985A JP H0516413 B2 JPH0516413 B2 JP H0516413B2
- Authority
- JP
- Japan
- Prior art keywords
- japanese knotweed
- houtt
- substance
- reynoutria
- reynoutria japonica
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 240000001341 Reynoutria japonica Species 0.000 claims description 31
- 235000018167 Reynoutria japonica Nutrition 0.000 claims description 31
- 208000007536 Thrombosis Diseases 0.000 claims description 22
- -1 stilbene compound Chemical class 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 12
- PJANXHGTPQOBST-VAWYXSNFSA-N Stilbene Natural products C=1C=CC=CC=1/C=C/C1=CC=CC=C1 PJANXHGTPQOBST-VAWYXSNFSA-N 0.000 claims description 8
- 235000021286 stilbenes Nutrition 0.000 claims description 8
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 claims description 5
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 claims description 5
- HSTZMXCBWJGKHG-OUUBHVDSSA-N piceide Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(C=CC=2C=CC(O)=CC=2)=C1 HSTZMXCBWJGKHG-OUUBHVDSSA-N 0.000 claims description 5
- 235000021283 resveratrol Nutrition 0.000 claims description 5
- 229940016667 resveratrol Drugs 0.000 claims description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 3
- 239000004615 ingredient Substances 0.000 claims description 3
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical class CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 239000000843 powder Substances 0.000 description 10
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- 102000003820 Lipoxygenases Human genes 0.000 description 7
- 108090000128 Lipoxygenases Proteins 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
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- KGIJOOYOSFUGPC-MSFIICATSA-N 5-Hydroxyeicosatetraenoic acid Chemical compound CCCCCC=CCC=CCC=C\C=C\[C@@H](O)CCCC(O)=O KGIJOOYOSFUGPC-MSFIICATSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 208000025865 Ulcer Diseases 0.000 description 3
- 230000017531 blood circulation Effects 0.000 description 3
- 238000013329 compounding Methods 0.000 description 3
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- 239000000047 product Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- XNRNNGPBEPRNAR-JQBLCGNGSA-N thromboxane B2 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1OC(O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O XNRNNGPBEPRNAR-JQBLCGNGSA-N 0.000 description 3
- 231100000397 ulcer Toxicity 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 2
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- 206010061218 Inflammation Diseases 0.000 description 2
- 241000219050 Polygonaceae Species 0.000 description 2
- 244000269722 Thea sinensis Species 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 210000003989 endothelium vascular Anatomy 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 150000002617 leukotrienes Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 238000011282 treatment Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- ZNHVWPKMFKADKW-UHFFFAOYSA-N 12-HETE Chemical compound CCCCCC=CCC(O)C=CC=CCC=CCCCC(O)=O ZNHVWPKMFKADKW-UHFFFAOYSA-N 0.000 description 1
- ZNHVWPKMFKADKW-ZYBDYUKJSA-N 12-HETE Natural products CCCCC\C=C/C[C@@H](O)\C=C\C=C/C\C=C/CCCC(O)=O ZNHVWPKMFKADKW-ZYBDYUKJSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 244000184734 Pyrus japonica Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000227654 Reynoutria Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 238000007602 hot air drying Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 238000004451 qualitative analysis Methods 0.000 description 1
- 239000000941 radioactive substance Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000007395 thrombosis prophylaxis Methods 0.000 description 1
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- 210000001519 tissue Anatomy 0.000 description 1
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Landscapes
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
（産業上の利用分野）
この発明は血栓等予防物質に係り、その目的は
血栓の症状悪化原因である５−HETE等アラキ
ドン酸のリポキシゲナーゼ代謝物の産出を阻害し
て、抗血栓効果を期待できる血栓等予防物質の提
供にある。
（発明の背景）
一般に、血栓とは血管内で血液が固まつた状態
をいい、血管内皮の損傷、炎症、潰瘍等の現象が
あることによつてその箇所に血小板、栓球、白血
球、フイブリン、赤血球等が集まり、膠着血栓を
生じ、内腔狭窄や閉塞を生じる。
この血栓は、赤血球増加、水分欠乏、貧血、出
血、悪性潰瘍、肥満等の原因で生じ、静脈で生じ
た場合には血流の変化と血流鬱血が生じ、動脈で
生じた場合には末梢血行障害、組織の壊死等の状
態にいたるものと言われている。
この血栓は生化学的に見ると血管内皮の損傷、
炎症、潰瘍等の現象があることによつてその箇所
に血小板等の凝集が開始されるとアラキドン酸の
代謝物であるTXB2、HHTが遊離されこの
TXB2、HHTが更に血液の凝集を相乗的に促進
すると考えられている。
このアラキドン酸の代謝物であるTXB2、
HHTはシクロオキシゲナーゼの代謝によつて血
管壁を保護する作用をもつロイコトリエンへと変
換されるものであるが、一方アラキドン酸はリポ
キシゲナーゼにより５−HETE、12−HETEへ
と代謝されロイコトリエンの拮抗物質であるプロ
スタグラジンへと代謝されるため、このアラキド
ン酸のリポキシゲナーゼ代謝物の産出を阻害す
る、即ちアラキドン酸の代謝酵素であるリポキシ
ゲナーゼの活性を特異的（選択的）に阻害するも
のは前記血栓症の予防能が極めて高いと考えられ
ている。
（従来技術及びその欠点）
従来のこのような血栓症に対するは治療法とし
ては、酸性ムコ多糖類であるヘパリンの投与等が
行われているが、通常は外科的手法でしか現在の
ところ有効な治療法はないとされている。
（発明の経過）
そこでこの発明者は、上記従来の欠点を悉く解
消するため前記したリポキシゲナーゼの特異的
（選択的）な阻害剤の発見につとめたところ、従
来葉が煙草の代用として用いられていたりあるい
は茶用に喫飲されていたタデ科植物であるイタド
リ（Reynoutria japonica Houtt）にその作用が
あることを見いだし、このイタドリ
（Reynoutria japonica Houtt）及び／又はこの
イタドリから抽出された抽出物を医薬品或いは食
品として施用させると前記血栓症状等の予防、解
消に効果をもつことを見いだし、この発明に到達
した。
（解決手段）
即ち、この発明ではイタドリ（Reynoutria
japonica Houtt）及び／又はこのイタドリ
（Reynoutria japonica Houtt）から抽出された
抽出物、特にこのイタドリから抽出された抽出物
が下記構造式(1)で示されるスチルベン化合物を含
むことを特徴とする血栓等予防物質を提供するこ
とにより前記従来の課題を悉く解消する。
［R1＝R2＝Ｈのときはレスベラトロール、R1
＝Ｄ−グルコース、R2＝Ｈのときはピセイド、
R1＝Ｈ、R2＝０−Ｄ−グルコースのときは２，
３，５，4′−テトラヒドロキシスチルベン−２−
０−Ｄ−グルコサイド］
（発明の構成）
この発明で使用するイタドリ（Reynoutria
japonica Houtt）とは全てタデ科の多年草であ
り、この全部位（地上部または地下部（塊根、根
底、根）、あるいは種子などが限定されることな
く好適に使用できるが、中でも特に根を原材料と
して好適に使用できる。
この発明において、イタドリの乾燥粉末を得る
には、まず公知の天然乾燥、熱風乾燥、あるいは
凍結乾燥のいずれかの手段で乾燥させ、該乾燥物
を公知の機械粉砕（ボールミル・スクリユー）に
よつて粉末化する。この発明においてはこの粉末
も必須配合成分として有効に利用できる。
次いで上記乾燥粉末からその抽出物を以下のよ
うにして得る。
まず、非乾燥イタドリを細切りし、この細切り
物又は前記乾燥粉末を低級脂肪族アルコールで抽
出する。
この抽出液を濃縮するか又は乾固して使用すれ
ばこの発明に係る血栓等予防物質の必須成分とす
ることができる。
或いは、前記細切り物又は前記乾燥粉末をアセ
トン−メタノールで抽出し、濾過し、濾液を更に
エチルエーテルで抽出し、このエチルエーテル難
溶部分をカラムクロマトで精製及びエタノールで
再精製すれば、下記スチルベン化合物が無色の結
晶状で得られる。
勿論、必ずしもスチルベン化合物にまで精製し
なくとも、前記エチルエーテル難溶部分を単に蒸
発乾固させてもこの発明に係る血栓等予防食品の
構成成分とすることができる。
この発明においてはこの濃縮液の段階でも必須
配合成分として利用できるし、又乾固物の段階で
も配合成分とすることができる。
この様にして得られたスチルベン化合物とは次
式(1)にて示されるレスベラトロール、ピセイド、
２，３，５，4′−テトラヒドロキシスチルベン−
２−０−Ｄ−グルコサイドからなる化合物であ
る。
［R1＝R2＝Ｈのときはレスベラトロール、R1
＝Ｄ−グルコース、R2＝Ｈのときはピセイド、
R1＝Ｈ、R2＝０−Ｄ−グルコースのときは２，
３，５，4′−テトラヒドロキシスチルベン−２−
０−Ｄ−グルコサイド］
以上の様なイタドリ（Reynoutria japonica
Houtt）の乾燥粉末あるいはこのイタドリ
（Reynoutria japonica Houtt）から抽出された
抽出物（必須に応じて精製されたスチルベン化合
物）を必須成分として、この発明に係る血栓等予
防物質とするには、通常被用者が一日に200mg乃
至1000mg程度のイタドリ等乾燥粉末を施用できる
様な任意の医薬品、食品形態とすればよい。
その形態例を具体的に例示すると、散剤、果粒
剤、錠剤、内服液、清涼飲料水、菓子等が挙げら
れる。
この発明においては、このような任意の医薬
品、食品形態とするに際して、常法に準じ、賦形
剤、増量剤、甘味料、香料を添加して調製すれば
良い。
（発明の効果）
以上の如くこの発明に係る血栓等予防物質は、
イタドリ（Reynoutria japonica Houtt）及び／
又はこのイタドリ（Reynoutria japonica
Houtt）から抽出された抽出物を必須成分として
なる血栓等予防物質であるから、血栓症の症状悪
化原因である５−HETE等のアラキドン酸のリ
ポキシゲナーゼ代謝物の産出を下記試験例の如く
特異的（選択的）に阻害することができ、従つて
血栓症の予防能が極めて高い食品である。
尚、この発明に係る血栓等予防物質を食品形態
に調製した場合には、医薬品でないので治療にあ
たつて医師の診断と指示を仰ぐ必要がなく、家庭
で手軽に施用できる効果を奏する。
以下この発明に係る血栓等予防物質の実施例及
び試験例を記載することにより、この発明の効果
をより一層明確なものとする。
（実施例）
イタドリ（Reynoutria japonica Houtt）の根
茎、根の乾燥粉砕物15Kgをｎ−ヘキサン10で２
回脱脂し脱脂後のイタドリ根13.2Kgをアセトン−
メタノール（１：１）20で抽出した。
この抽出液を0.5に濃縮した後、この濃縮物
をエチルエーテル５で抽出し、抽出残査をケイ
酸カラムでエタノールを用いて、白色結晶を得
た。
この結果は600g得られた。
この結晶を薄層クロマトグラフで定性分析した
ところ、レスベラトロール、ピセイド、２，３，
５，4′−０−Ｄ−グルコサイドであつた。
（試験例）
ウイスター系♂ラツトを使用し、このラツト腹
腔内多核白血球をHEPS−生食緩衝液（PH7.4）
で洗浄し、同緩衝液に懸濁、超音波処理を行なつ
たものをアラキドン酸代謝の酵素液として用い
た。この血小板ホモジネイトと各スチルベン化合
物及びイタドリ粉末さらにはブランクのそれぞれ
のサンプルを次表に示す種々の濃度に調製し、37
℃、５分間保温し、その後〔１−14C〕アラキド
ン酸（0.05μCi）を加え五分間インキユベイトし
た。
終了後、反応をギ酸で止め（PH３）アラキドン
酸代謝産物を酢酸エチルで抽出し、シリカゲル薄
層クロマトグラフイ（TLC）で分離して定量し
た（展開液：石油エーテル：エーテル：酢酸＝
50：50：１、Ｖ／Ｖ、TLCはメルク5748）。放射
活性物質はオートラジオグラフイで検出し、その
スポツトを切取り、放射活性を液体シンチレーシ
ヨンカウンターで定量した。
以下、試験結果を第１乃至第２表にまとめて示
す。
(Industrial Application Field) This invention relates to a substance that prevents thrombosis, etc., and its purpose is to inhibit the production of lipoxygenase metabolites of arachidonic acid such as 5-HETE, which are the cause of worsening symptoms of thrombosis, so that an antithrombotic effect can be expected. The goal is to provide substances that prevent blood clots. (Background of the Invention) Generally, a thrombus is a state in which blood clots within a blood vessel, and due to phenomena such as damage to the vascular endothelium, inflammation, or ulcer, platelets, thrombocytes, white blood cells, and fibrin are present at the site. , red blood cells, etc. gather and form a sticky thrombus, resulting in lumen narrowing and occlusion. This thrombus occurs due to causes such as increased red blood cells, water deficiency, anemia, bleeding, malignant ulcers, and obesity.When it occurs in a vein, it causes changes in blood flow and blood flow congestion, and when it occurs in an artery, it causes peripheral blood clots. It is said to lead to conditions such as blood circulation disorders and tissue necrosis. From a biochemical perspective, this thrombus is caused by damage to the vascular endothelium.
When platelets, etc. start aggregating at the site due to a phenomenon such as inflammation or ulcer, TXB2 and HHT, which are metabolites of arachidonic acid, are released.
TXB2 and HHT are also thought to synergistically promote blood aggregation. TXB2, a metabolite of this arachidonic acid,
HHT is converted by cyclooxygenase into leukotrienes that protect blood vessel walls, while arachidonic acid is metabolized by lipoxygenase into 5-HETE and 12-HETE, which are antagonists of leukotrienes. Since it is metabolized to prostaglandin, substances that inhibit the production of lipoxygenase metabolites of arachidonic acid, that is, those that specifically (selectively) inhibit the activity of lipoxygenase, which is an enzyme metabolizing arachidonic acid, are required to prevent the above-mentioned thrombosis. It is considered to have extremely high preventive ability. (Prior art and its drawbacks) Conventional treatments for such thrombosis include administration of heparin, an acidic mucopolysaccharide, but currently only surgical methods are effective. There is said to be no cure. (Progress of the Invention) Therefore, in order to eliminate all of the above-mentioned conventional drawbacks, the inventor endeavored to discover a specific (selective) inhibitor of lipoxygenase, and found that the leaves had not been previously used as a substitute for cigarettes. It was discovered that Japanese knotweed (Reynoutria japonica Houtt), a plant of the Polygonaceae family that was consumed as tea or as a tea, had this effect. Alternatively, it was discovered that when applied as a food, it is effective in preventing and eliminating the thrombotic symptoms, etc., and the present invention was achieved. (Solution) That is, in this invention, Japanese knotweed (Reynoutria
japonica Houtt) and/or an extract extracted from this Japanese knotweed (Reynoutria japonica Houtt), particularly a thrombus characterized in that the extract extracted from this Japanese knotweed contains a stilbene compound represented by the following structural formula (1). By providing a preventive substance, all of the above-mentioned conventional problems are solved. [When R 1 = R 2 = H, resveratrol, R 1
= D-glucose, when R 2 = H, piceide,
2 when R 1 = H, R 2 = 0-D-glucose,
3,5,4'-tetrahydroxystilbene-2-
0-D-glucoside] (Structure of the invention) Japanese knotweed (Reynoutria) used in this invention
japonica Houtt) is a perennial plant of the Polygonaceae family, and all parts of this plant (above-ground parts, underground parts (tubers, basal roots, roots), seeds, etc.) can be suitably used without limitation, but especially roots can be used as raw materials. In the present invention, in order to obtain a dry powder of Japanese knotweed, it is first dried by any of known natural drying, hot air drying, or freeze drying, and then the dried product is pulverized by a known mechanical pulverization (ball mill). - Screw). In this invention, this powder can also be effectively used as an essential compounding ingredient. Next, the extract is obtained from the above dry powder as follows. First, non-dried Japanese knotweed is cut into small pieces. This shredded product or the dried powder is extracted with a lower aliphatic alcohol. If this extract is concentrated or dried and used, it can be used as an essential component of the thrombosis prevention substance according to the present invention. , the shredded material or the dried powder is extracted with acetone-methanol, filtered, the filtrate is further extracted with ethyl ether, and the ethyl ether hardly soluble portion is purified by column chromatography and repurified with ethanol to obtain the following stilbene compound. is obtained in the form of colorless crystals.Of course, without necessarily refining it to a stilbene compound, the ethyl ether hardly soluble portion can be simply evaporated to dryness and used as a component of the food for preventing blood clots, etc. according to the present invention. In this invention, it can be used as an essential compounding component even at the stage of this concentrated liquid, and it can also be used as a compounding component at the stage of a dry product.The stilbene compound obtained in this way has the following formula (1 ), resveratrol, piceide,
2,3,5,4'-tetrahydroxystilbene-
It is a compound consisting of 2-0-D-glucoside. [When R 1 = R 2 = H, resveratrol, R 1
= D-glucose, when R 2 = H, piceide,
2 when R 1 = H, R 2 = 0-D-glucose,
3,5,4'-tetrahydroxystilbene-2-
0-D-Glucoside] Japanese knotweed (Reynoutria japonica) as shown above
In order to use the dry powder of Reynoutria japonica Houtt or the extract (stilbene compound purified as required) from this Japanese knotweed (Reynoutria japonica Houtt) as an essential ingredient, the substance for preventing blood clots, etc. according to the present invention must be prepared by a normal employee. It may be in any pharmaceutical or food form that allows for the application of dry powder such as Japanese knotweed in an amount of about 200 mg to 1000 mg per day. Specific examples of the form include powders, granules, tablets, oral solutions, soft drinks, and confectionery. In the present invention, any pharmaceutical or food form may be prepared by adding excipients, fillers, sweeteners, and flavors according to conventional methods. (Effect of the invention) As described above, the substance for preventing blood clots, etc. according to the present invention is as follows:
Japanese knotweed (Reynoutria japonica Houtt) and/
Or this Japanese knotweed (Reynoutria japonica)
Since it is a thrombosis preventive substance that contains an extract extracted from Houtt as an essential component, it specifically inhibits the production of lipoxygenase metabolites of arachidonic acid such as 5-HETE, which are the cause of worsening symptoms of thrombosis, as shown in the test example below. Therefore, it is a food with extremely high ability to prevent thrombosis. Furthermore, when the thrombus prevention substance according to the present invention is prepared in the form of a food, it is not a pharmaceutical, so there is no need to seek diagnosis and instructions from a doctor for treatment, and the effect can be easily applied at home. The effects of the present invention will be made clearer by describing Examples and Test Examples of the substance for preventing thrombosis, etc. according to the present invention. (Example) 15 kg of dried pulverized rhizomes and roots of Japanese knotweed (Reynoutria japonica Houtt) was mixed with 10 ml of n-hexane.
13.2Kg of Japanese knotweed roots after being defatted and defatted are mixed with acetone.
Extracted with 20 methanol (1:1). After concentrating this extract to a concentration of 0.5, this concentrate was extracted with ethyl ether 5, and the extraction residue was passed through a silicic acid column using ethanol to obtain white crystals. The result was 600g. Qualitative analysis of this crystal by thin layer chromatography revealed that resveratrol, piceide, 2,3,
It was 5,4'-0-D-glucoside. (Test example) Wistar male rats were used, and their intraperitoneal polynuclear leukocytes were collected in HEPS-saline buffer (PH7.4).
The sample was washed with water, suspended in the same buffer, and subjected to ultrasonication, and used as an enzyme solution for arachidonic acid metabolism. Samples of this platelet homogenate, each stilbene compound, Japanese knotweed powder, and a blank were prepared at various concentrations shown in the table below.
C. for 5 minutes, then [ 1-14 C] arachidonic acid (0.05 μCi) was added and incubated for 5 minutes. After completion, the reaction was stopped with formic acid (PH3), and arachidonic acid metabolites were extracted with ethyl acetate, separated and quantified by silica gel thin layer chromatography (TLC) (developing solution: petroleum ether: ether: acetic acid =
50:50:1, V/V, TLC is Merck 5748). Radioactive substances were detected by autoradiography, the spots were excised, and the radioactivity was quantified using a liquid scintillation counter. The test results are summarized in Tables 1 and 2 below.
【表】【table】
【表】【table】
【表】【table】
【表】
以上の結果明らかな如く、この発明で使用する
イタドリ粉末及びスチルベン化合物はリポキシゲ
ナーゼの酵素活性を阻害するものとして優れた効
果を奏し、即ちこの発明に係る血栓等予防物質は
血栓等予防効果に優れた効果を奏すことが判る。[Table] As is clear from the above results, the Japanese knotweed powder and the stilbene compound used in this invention have excellent effects as inhibitors of lipoxygenase enzyme activity. It turns out that it has an excellent effect.
Claims (1)
び／又はこのイタドリ（Reynoutria japonica
Houtt）から抽出された抽出物を必須成分として
なる血栓等予防物質。 ２ 前記イタドリ（Reynoutria japonica
Houtt）から抽出された抽出物が下記構造式(1)で
示されるスチルベン化合物を含有してなることを
特徴とする特許請求の範囲第１項記載の血栓等予
防物質。 ［R1＝R2＝Ｈのときはレスベラトロール、R1
＝Ｄ−グルコース、R2＝Ｈのときはピセイド、
R1＝Ｈ、R2＝０−Ｄ−グルコースのときは２，
３，５，4′−テトラヒドロキシスチルベン−２−
０−Ｄ−グルコサイド］[Scope of Claims] 1 Japanese knotweed (Reynoutria japonica Houtt) and/or this Japanese knotweed (Reynoutria japonica
A substance that prevents blood clots, etc., whose essential ingredient is an extract extracted from Houtt. 2 The Japanese knotweed (Reynoutria japonica)
2. The substance for preventing thrombosis, etc. according to claim 1, characterized in that the extract extracted from A. Houtt contains a stilbene compound represented by the following structural formula (1). [When R 1 = R 2 = H, resveratrol, R 1
= D-glucose, when R 2 = H, piceide,
2 when R 1 = H, R 2 = 0-D-glucose,
3,5,4'-tetrahydroxystilbene-2-
0-D-glucoside]
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60011679A JPS61171427A (en) | 1985-01-24 | 1985-01-24 | Substance for preventing thrombosis or the like |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60011679A JPS61171427A (en) | 1985-01-24 | 1985-01-24 | Substance for preventing thrombosis or the like |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61171427A JPS61171427A (en) | 1986-08-02 |
| JPH0516413B2 true JPH0516413B2 (en) | 1993-03-04 |
Family
ID=11784678
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60011679A Granted JPS61171427A (en) | 1985-01-24 | 1985-01-24 | Substance for preventing thrombosis or the like |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61171427A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011089168A2 (en) | 2010-01-21 | 2011-07-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Special composition for the use thereof as a drug |
| WO2019016153A1 (en) | 2017-07-17 | 2019-01-24 | L'oreal | Aqueous cosmetic composition comprising a pyridinedicarboxylic acid derivative and a hydroxystilbene |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1256354B (en) * | 1992-08-31 | 1995-12-01 | Francesca Pelizzoni | ANTI-TUMORAL ACTIVITIES OF COMBRETASTATINA AND PROCEDURE FOR THEIR PREPARATION |
| FR2766176B1 (en) * | 1997-07-15 | 1999-10-29 | Caudalie | COMPOSITIONS BASED ON RESVERATROL DERIVATIVES |
| FR2778337B1 (en) * | 1998-05-05 | 2001-08-31 | Inst Nat Sante Rech Med | ARYLHYDROCARBON RECEPTOR LIGAND ANTAGONISTS |
| AU2003268599B2 (en) * | 1998-05-05 | 2007-03-15 | Casper, Robert Frederic | Arylhydrocarbon Receptor Ligand Antagonists |
| AU4084599A (en) * | 1998-05-18 | 1999-12-06 | Oklahoma Medical Research Foundation | Resveratrol inhibition of myeloperoxidase |
| EP1147207A1 (en) * | 1999-01-29 | 2001-10-24 | The Samuel Roberts Noble Foundation, Inc. | Transgenic plants modified to contain resveratrol glucoside and uses thereof |
| US6974895B1 (en) | 1999-01-29 | 2005-12-13 | The Samuel Roberts Noble Foundation, Inc. | Transgenic legume plants modified to produce resveratrol glucoside and uses thereof |
| AU7596100A (en) | 1999-09-21 | 2001-04-24 | Rutgers, The State University | Resveratrol analogs for prevention of disease |
| CN1090603C (en) * | 1999-09-24 | 2002-09-11 | 四川省凉山州生物研究所 | Process for extracting resveratrol from Chinese medicine giant knotweed root |
| CN1398838A (en) | 2001-07-26 | 2003-02-26 | 中国人民解放军军事医学科学院放射医学研究所 | Diphenylethylene compound and its prepn and application in preventing and treating diabetes |
| CN105726508B (en) * | 2016-01-12 | 2019-02-15 | 中国人民解放军第四军医大学 | Novel stilbene glycoside sustained and controlled release preparation and preparation method thereof |
| KR102040763B1 (en) * | 2017-10-27 | 2019-11-05 | 한약진흥재단 | Anti-thrombus agent comprising extract of Polygonum cuspidatum Sieb. et Zucc. and Cinnamomum cassia Blume |
| CN107722079A (en) * | 2017-10-31 | 2018-02-23 | 桂林纽泰生物科技有限公司 | The method that Stibene-glucoside is extracted from the fleece-flower root |
| CN107903292B (en) * | 2017-12-26 | 2020-10-30 | 四川文理学院 | Method for extracting stilbene glucoside from polygonum multiflorum |
| KR102305237B1 (en) * | 2019-07-29 | 2021-09-29 | 재단법인 경기도경제과학진흥원 | Compositions for Improving Skin Wrinkles and Skin Whitening Using an Extract of Persicaria filiforme |
-
1985
- 1985-01-24 JP JP60011679A patent/JPS61171427A/en active Granted
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011089168A2 (en) | 2010-01-21 | 2011-07-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Special composition for the use thereof as a drug |
| WO2019016153A1 (en) | 2017-07-17 | 2019-01-24 | L'oreal | Aqueous cosmetic composition comprising a pyridinedicarboxylic acid derivative and a hydroxystilbene |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61171427A (en) | 1986-08-02 |
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