JPH02264719A - Anticonvulsant - Google Patents
AnticonvulsantInfo
- Publication number
- JPH02264719A JPH02264719A JP8629689A JP8629689A JPH02264719A JP H02264719 A JPH02264719 A JP H02264719A JP 8629689 A JP8629689 A JP 8629689A JP 8629689 A JP8629689 A JP 8629689A JP H02264719 A JPH02264719 A JP H02264719A
- Authority
- JP
- Japan
- Prior art keywords
- anticonvulsant
- active ingredient
- epigallocatechin
- anticonvulsant agent
- oral
- 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.)
- Pending
Links
- 239000001961 anticonvulsive agent Substances 0.000 title claims abstract description 12
- 230000001773 anti-convulsant effect Effects 0.000 title claims abstract description 8
- 229960003965 antiepileptics Drugs 0.000 title claims description 4
- XMOCLSLCDHWDHP-IUODEOHRSA-N epi-Gallocatechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@H]2O)=CC(O)=C(O)C(O)=C1 XMOCLSLCDHWDHP-IUODEOHRSA-N 0.000 claims abstract description 27
- 239000004480 active ingredient Substances 0.000 claims abstract description 11
- 229940125681 anticonvulsant agent Drugs 0.000 abstract description 8
- 238000002347 injection Methods 0.000 abstract description 6
- 239000007924 injection Substances 0.000 abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 abstract description 5
- 239000001301 oxygen Substances 0.000 abstract description 5
- -1 oxygen free radical Chemical class 0.000 abstract description 4
- 229920001864 tannin Polymers 0.000 abstract description 4
- 239000001648 tannin Substances 0.000 abstract description 4
- 235000018553 tannin Nutrition 0.000 abstract description 4
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 238000007911 parenteral administration Methods 0.000 abstract description 3
- LSHVYAFMTMFKBA-TZIWHRDSSA-N (-)-epicatechin-3-O-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=CC=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 LSHVYAFMTMFKBA-TZIWHRDSSA-N 0.000 abstract description 2
- 241000196324 Embryophyta Species 0.000 abstract description 2
- 239000002775 capsule Substances 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 239000006187 pill Substances 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 abstract description 2
- 239000000470 constituent Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 229940126701 oral medication Drugs 0.000 abstract 1
- XMOCLSLCDHWDHP-UHFFFAOYSA-N L-Epigallocatechin Natural products OC1CC2=C(O)C=C(O)C=C2OC1C1=CC(O)=C(O)C(O)=C1 XMOCLSLCDHWDHP-UHFFFAOYSA-N 0.000 description 11
- 206010010904 Convulsion Diseases 0.000 description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 7
- 230000036461 convulsion Effects 0.000 description 6
- 229910052742 iron Inorganic materials 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 241000700159 Rattus Species 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 241001122767 Theaceae Species 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 210000003710 cerebral cortex Anatomy 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical class O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 description 1
- 108010029908 3-oxo-5-alpha-steroid 4-dehydrogenase Proteins 0.000 description 1
- 102000001779 3-oxo-5-alpha-steroid 4-dehydrogenase Human genes 0.000 description 1
- 229940113178 5 Alpha reductase inhibitor Drugs 0.000 description 1
- 239000002677 5-alpha reductase inhibitor Substances 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 241000238557 Decapoda Species 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001765 catechin Chemical class 0.000 description 1
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 1
- 235000005487 catechin Nutrition 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229920002770 condensed tannin Polymers 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 208000028329 epileptic seizure Diseases 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 230000007760 free radical scavenging Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、所謂茶タンニンの主構成分である茶カテキン
類の（−）エピガロカテキンを有効成分とする抗けいれ
ん剤に関するものである。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to an anticonvulsant agent containing (-)epigallocatechin, a tea catechin class, as an active ingredient, which is a main component of so-called tea tannins.
けいれんの発現機構に関しては、現在まで様々な研究が
行われているが、外傷性けいれんについては、頭部外傷
後の脳内出血時に、鉄イオンにより活性酸素フリーラジ
カルが発生し、これが原因となってけいれんが発生する
との発表がある〔プレイ゛ン リサーチ （Ｂｒａｉｎ
、 Ｒｅｓ、 ）２２７．３９３ （１９８３＞、病態
生理、 ：３．８５６（１９８４） ）。Various studies have been conducted to date regarding the mechanism of convulsions, but the cause of traumatic convulsions is that active oxygen free radicals are generated by iron ions during intracerebral hemorrhage after head trauma. There is an announcement that convulsions occur [Brain Research (Brain Research)]
, Res, ) 227.393 (1983>, Pathophysiology, : 3.856 (1984)).
また、本発明者等は先に天然植物中のタンニン化合物が
強力な活性酸素フリーラジカル消去作用を有することを
見出し、縮合型タンニンを佇効成分とする活性酸素フリ
ーラジカル消去剤を発明した【特開昭６４−２５７２６
号公報）
更に、茶カテキン類の（−）エピガロカテキンはダラム
陰性菌阻害抗菌剤（特開昭６１−１０６５１０号公報）
、皮膚常在菌に対して抑制効果を示す抗菌剤（特開昭６
２−１４５０１６号公報）、テストステロン５α−レダ
ククーゼ阻害剤（特開昭６２−８４０２１号公報）とし
てそれぞれ開示されている。In addition, the present inventors have previously discovered that tannin compounds in natural plants have a strong active oxygen free radical scavenging effect, and have invented an active oxygen free radical scavenger containing condensed tannin as an active ingredient. Kaisho 64-25726
In addition, (-)epigallocatechin of tea catechins is an antibacterial agent that inhibits Durham-negative bacteria (Japanese Patent Application Laid-open No. 106510/1982).
, an antibacterial agent that shows an inhibitory effect on resident bacteria on the skin (Unexamined Japanese Patent Publication No. 6
2-145016) and a testosterone 5α-reductase inhibitor (Japanese Unexamined Patent Publication No. 62-84021).
従来、けいれんに対し有効でしかも副作用のない抗けい
れん剤はなく、強く要望されている。So far, there has been no anticonvulsant agent that is effective against convulsions and has no side effects, and there is a strong demand for such agents.
本発明はこの要望に適合した抗けいれん剤を提供するこ
とを目的とするものである。The object of the present invention is to provide an anticonvulsant that meets this need.
本発明者等は活性酸素フリーラジカルを消去する作用を
有する天然随物中のタンニン化合物中、特に茶タンニン
の構成分である（−）エビがロカテキンが抗けいれん作
用を顕著に有することを見出し本発明を完成した。The present inventors discovered that among the tannin compounds in natural substances that have the effect of scavenging active oxygen free radicals, locatechin in (-) shrimp, which is a component of tea tannin, has a remarkable anticonvulsant effect. Completed the invention.
本発明は（−）エピガロカテキンを有効成分とする抗け
いれん剤である。The present invention is an anticonvulsant agent containing (-)epigallocatechin as an active ingredient.
本発明の有効成分である（−）エピガロカテキン（以下
ＥＧＣと称す）はケミカル アンド ファーマシューテ
イ力ル ブレチア （Ｃｈｅｍ、Ｐｈａｒｍ。(-)Epigallocatechin (hereinafter referred to as EGC), which is the active ingredient of the present invention, is available from Chemical and Pharmacy Co., Ltd. (Chem, Pharm).
Ｂｕｌｌ）３］ 、３９０６． （１９８３）により製
造される公知物質である。Bull) 3], 3906. (1983).
本発明の有効成分であるＥＧＣを抗けいれん剤として人
に投与する場合は、経口的及び非経口的の何れによって
もよく、その製剤形態は錠剤、丸剤、カプセル剤、液剤
等の経口剤、注射剤等の非経口剤に通常の医薬品の製剤
に用いられる担体、補助剤等を用いて通常の製剤法によ
り得ることができる。When administering EGC, which is the active ingredient of the present invention, to humans as an anticonvulsant agent, it may be administered either orally or parenterally, and its formulation may include oral preparations such as tablets, pills, capsules, and liquid preparations. It can be obtained by a normal formulation method using carriers, adjuvants, etc. used in the formulation of ordinary pharmaceuticals for parenteral preparations such as injections.
ＥＧＣの投与中は、症状の程度により適宜勘案して決め
られるが、通常、経口的には２０〜２００ｍｇ、非経口
的には１０〜１００ｍｇ程度が適当である。The dosage of EGC is determined by taking into account the severity of the symptoms, but the appropriate dosage is usually 20 to 200 mg for oral administration and 10 to 100 mg for parenteral administration.
Ｅ Ｇ Ｃの毒性は、急性毒性試験で、ｄｄｙ系雄性マ
ウス（体重：２０〜３０ｇ）にＥＧＣを経口投与した場
合、５０００ｍｇ／ｋｇ においても、１週間経過後死
亡例はなかった。Regarding the toxicity of EGC, in an acute toxicity test, when EGC was orally administered to ddy male mice (body weight: 20 to 30 g), there was no death after one week even at a dose of 5000 mg/kg.
また、ＥＧＣを腹腔内投与した場合、１０００ｍｇ／ｋ
ｇにおいても、１週間経過後死亡例はなかった。In addition, when EGC is administered intraperitoneally, 1000 mg/k
There were no cases of death after 1 week in G.
本発明の有効成分であるＥ Ｇ Ｃの抗けいれん作用を
示す試験例を挙げる。A test example showing the anticonvulsant effect of EGC, which is the active ingredient of the present invention, will be given below.
試験例 鉄イオン誘発けいれん抑制作用試験（方法）
体重２５０〜３５０ｇのＳ、 Ｄ、系雄性ラットをサタ
ンニルコリンで非動化し、人工呼吸下に試験を行った。Test Example Iron ion-induced convulsion suppression effect test (method) S, D, male rats weighing 250 to 350 g were immobilized with satanylcholine and tested under artificial respiration.
左右前頭部及び左右後頭部に硬膜外ビス電極を植立し、
脳波記録用とした。Epidural screw electrodes were implanted in the left and right frontal regions and the left and right occipital regions,
It was used for electroencephalogram recording.
塩化第二鉄の溶液（１００ｍ Ｍ ） をプレグ７
（ｂｒｅｇｍａ）より左方１ｍｍ、後方１ｍｍの大脳皮
質感覚運動野に５μβを注入し、その後２５〜５０ｍｇ
／ｋｇのＥＧＣを１＋ｎｊ！の生理食塩水に溶解し、大
腿静脈から０．２ｍ７！／ｍｉｎの速度で注入した。対
照群のラットには、鉄注入後に５０ｍｇ／ ｋｇのショ
糖を含む生理食塩水を注入し、脳波を観察した。Preg 7 with a solution of ferric chloride (100 mM)
Inject 5μβ into the sensorimotor cortex of the cerebral cortex 1mm left and 1mm behind (bregma), then 25-50mg
/kg of EGC is 1+nj! Dissolved in physiological saline, 0.2 m7 from the femoral vein! The injection was performed at a rate of /min. Rats in the control group were injected with physiological saline containing 50 mg/kg of sucrose after iron injection, and their brain waves were observed.
（結果）
対照群のラット脳波には、鉄注入３０〜６０分後より鉄
投与側よりＨａ（ｓｐ ＋ ｋｅ） が出現し始め、
１．０〜ｌ、５時間後より大脳皮質の両側からてんかん
発作パターンが５〜１０分間隔で繰り返し出現した。(Results) In the brain waves of rats in the control group, Ha(sp + ke) began to appear from the iron-administered side 30 to 60 minutes after iron injection.
From 1.0 to 1.5 hours later, epileptic seizure patterns appeared repeatedly at 5 to 10 minute intervals from both sides of the cerebral cortex.
扶投与直後に５０ ｍｇ／ ｋｇのＥ Ｇ Ｃを投与す
ると、３．０〜３．５時間の間輔波活動は見ろれなかっ
た。また、２５ ｍｇ／ ｋｇの投与でも練液活動は殆
ど認められなかった。When 50 mg/kg of EGC was administered immediately after administration of EGC, no electromagnetic wave activity was observed for 3.0 to 3.5 hours. Furthermore, even after administration of 25 mg/kg, almost no liquid elaboration activity was observed.
これを図面に示すと、第１図の通りである。This is illustrated in FIG. 1.
次に本発明の実施例を示す。Next, examples of the present invention will be shown.
例 Ｉ
８６０５０ｇ
乳 糖 ３００ｇ
酒石酸 １０ｇ
ステアリン酸マグネシウム ２ｇ
以上をとり、結合剤として５％搬粉糊液を使用し、湿式
法で顆粒を製し、これを打錠機により打錠して錠剤１０
００個を得た。Example I: Take 86050 g of lactose, 300 g of tartaric acid, 2 g of magnesium stearate, prepare granules using a wet method using 5% starch paste as a binder, and press the granules with a tablet machine to make 10 tablets.
Obtained 00 pieces.
例 ２
ＥＧＣ５（ｌｎｇを注射用蒸留水２０ｍ１に溶かし、凍
結乾燥して静脈注射剤とした。Example 2 EGC5 (lng) was dissolved in 20 ml of distilled water for injection and lyophilized to prepare an intravenous injection.
本発明は極めて優れた抗けいれん作用を有し、しかも毒
性のない有用な抗けいれん剤である。The present invention is a useful anticonvulsant that has extremely excellent anticonvulsant effects and is not toxic.
【図面の簡単な説明】
第１図は本発明の有効成分であるＥＧＣの鉄イオン誘発
けいれんを抑制する試験結果を図示したものである。
特許出願人 祐徳薬品工業株式会社BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 illustrates the test results of EGC, which is the active ingredient of the present invention, in suppressing convulsions induced by iron ions. Patent applicant Yutoku Pharmaceutical Co., Ltd.
Claims (1)
ん剤。1.An anticonvulsant containing (-)epigallocatechin as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8629689A JPH02264719A (en) | 1989-04-04 | 1989-04-04 | Anticonvulsant |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8629689A JPH02264719A (en) | 1989-04-04 | 1989-04-04 | Anticonvulsant |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH02264719A true JPH02264719A (en) | 1990-10-29 |
Family
ID=13882874
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8629689A Pending JPH02264719A (en) | 1989-04-04 | 1989-04-04 | Anticonvulsant |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02264719A (en) |
-
1989
- 1989-04-04 JP JP8629689A patent/JPH02264719A/en active Pending
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