JPH0830077B2 - Ischemic disease therapeutic agent - Google Patents
Ischemic disease therapeutic agentInfo
- Publication number
- JPH0830077B2 JPH0830077B2 JP62102583A JP10258387A JPH0830077B2 JP H0830077 B2 JPH0830077 B2 JP H0830077B2 JP 62102583 A JP62102583 A JP 62102583A JP 10258387 A JP10258387 A JP 10258387A JP H0830077 B2 JPH0830077 B2 JP H0830077B2
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- Japan
- Prior art keywords
- tanshinone
- heart
- therapeutic agent
- myocardial
- ischemic disease
- 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.)
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- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】 （発明の利用分野） 本発明は、漢薬「丹参」中のジテルペン成分タンシノ
ンＩ（TanshinoneI）を有効成分とする虚血性疾患治療
剤に関する。TECHNICAL FIELD The present invention relates to a therapeutic agent for ischemic disease containing, as an active ingredient, the diterpene component Tanshinone I in the Chinese medicine “Dansin”.
（従来の技術とその問題点） 狭心症や心筋梗塞のような虚血性疾患は、主として冠
状動脈の狭窄による心筋への血行障害により起こり、
癌、心不全と共に致死的成人病中重要な位置を占めてい
る。しかしこれまで本症の治療に用いられてきた薬剤
は、コレステロール低下剤や血管拡張剤が主流であっ
て、心筋細胞膜障害の抑制や虚血時における心筋保護を
意図した薬剤は開発されていない。(Prior art and its problems) Ischemic diseases such as angina and myocardial infarction occur mainly due to impaired blood circulation to the myocardium due to stenosis of coronary arteries.
It is important in fatal adult diseases along with cancer and heart failure. However, most of the drugs that have been used for the treatment of this disease so far are cholesterol-lowering drugs and vasodilators, and no drugs intended to suppress myocardial cell membrane damage or protect myocardium during ischemia have been developed.
近来に至り、古来の和漢薬の効果が見直され、植物由
来の漢薬の中、狭心痛の緩解及び冠状動脈の拡張に基づ
く心機能の回復や自覚症状（目まい、立ちくらみ、手足
の冷感）の改善効果を奏するとされるものも多数報告さ
れているが、それらの病態生理学的・薬理学的評価は乏
しく、とりわけそれらに含まれる心筋梗塞、狭心症等の
虚血性疾患に対する活性物質に関する研究は皆無に均し
い。In recent years, the effects of ancient Japanese herbs have been reviewed, and among the Chinese herbs derived from plants, recovery of anginal pain and recovery of heart function due to dilation of coronary arteries and subjective symptoms (dizziness, lightheadedness, cold sensation of limbs) ) Have been reported, but their pathophysiological and pharmacological evaluations are poor, and in particular, they are active substances for myocardial infarction, angina and other ischemic diseases. There is no research on it.
（発明の背景） 漢薬「丹参」（又は紫参）はシソ科（Labiatae）の植
物Salvia miltiorrhiza Bga.の根の乾燥物であって、従
来から漢方における理血薬（血行改善剤）として狭心
症、心筋梗塞の治療に利用されてきたが、その有効成分
に関してはこれまで知られていなかった。然るに本発明
者らは研究の結果、丹参中から単離されたタンシノンＩ
（Tanshinone I）、タンシノンII（Tanshinone II）、
ジヒドロタンシノン（Dihydrotanshinone）及びクリプ
トタンシノン（Cryptotanshinone）の四種のテルペノイ
ドその他の諸成分の中、独りタンシノンＩのみが虚血性
心疾患病態モデルによる検索の結果、再正常化時の心筋
収縮力回復の促進、冠状動脈血管の拡張及びATP代謝産
物の遊離抑制等の有意義な対虚血性疾患的薬理作用を有
すること、並びにその他の単離成分は、無効であるか又
は冠状動脈の収縮など、却って毒性作用を有する事実を
見出した。本発明はこれらの知見に基づくものである。(Background of the Invention) The Chinese medicine "Tan ginseng" (or purple ginseng) is a dried root of Salvia miltiorrhiza Bga., Which is a plant of Labiatae, and has been used as a blood medicine (blood circulation improving agent) in traditional Chinese medicine. It has been used for the treatment of cardiomyopathy and myocardial infarction, but its active ingredient has not been known so far. However, as a result of the research conducted by the present inventors, tanshinone I isolated from Danshenchu
(Tanshinone I), Tanshinone II (Tanshinone II),
Of the four terpenoids and other components of dihydrotanshinone and Cryptotanshinone, only tanshinone I alone was found in a model of ischemic heart disease, and as a result, recovery of myocardial contractile force during renormalization It has a significant anti-ischemic pharmacological action such as promotion of cerebral coronary artery, dilation of coronary blood vessels and inhibition of release of ATP metabolites, and other isolated components are ineffective or contraction of coronary arteries, etc. We have found the fact that it has a toxic effect. The present invention is based on these findings.
（発明の目的） 従って、本発明は丹参中の有効成分タンシノンＩを提
供することによって、虚血性心疾患の救急、治療及び予
防のため有効な手段を開発するのを目的とする。(Object of the Invention) Therefore, the present invention aims to develop an effective means for the rescue, treatment and prevention of ischemic heart disease by providing the active ingredient Tanshinone I in Danshen.
（目的達成のための手段） 以上の目的を達成するため、本発明の要旨は、タンシ
ノンＩ（Tanshinone I）を有効成分とする虚血性疾患治
療剤に存する。以下、発明に関連する重要な事項に付き
記載する。(Means for Achieving Object) In order to achieve the above object, the gist of the present invention resides in a therapeutic agent for ischemic disease containing Tanshinone I as an active ingredient. The important matters related to the invention will be described below.
［タンシノンＩの単離］ タンシノンＩは、市販の丹参（Salvia miltiorrhiza
Bge.の根の乾燥物）を原料として、例えばこれをヘキサ
ンで前抽出して不純物を除去した後、酢酸エチル、メタ
ノール等の溶媒で抽出し、次いでシリカゲルクロマト等
の慣用の精製手段を用いて精製することにより得られる
（第１図参照）。目的のタンシノンＩの他、類似構造を
有するタンシノンII、ジヒドロタンシノン及びクリプト
タンシノンが夫々単離、同定された。[Isolation of Tanshinone I] Tanshinone I is commercially available Danshen (Salvia miltiorrhiza).
Bge. Root dry matter) as a raw material, for example, this is pre-extracted with hexane to remove impurities, then extracted with a solvent such as ethyl acetate or methanol, and then using a conventional purification means such as silica gel chromatography. It is obtained by purification (see FIG. 1). In addition to the desired tanshinone I, tanshinone II, dihydrotanshinone and cryptotanshinone having similar structures were isolated and identified, respectively.
［タンシノンＩの構造、物理・化学的性状］ （Ａ）使用試薬及び機器 TLC-1（クロロホルム）、TLC-2（ヘキサン：酢酸エチル
＝8:2）、TLC-3（クロロホルム：メタノール＝1:1;セフ
ァデックスLH20（Pharmacia）． シリカゲル：キーゼルゲル60（70-230メッシュ）メル
ク；融点測定：柳本融点測定器、1HNMRJEOL PMX 60;MS
測定：島津質量分析計GCMS-6020、IR測定:Shimadzu IR-
420、UV測定:Shimadzu分光光度計UV-260。[Structure, physical and chemical properties of tanshinone I] (A) Reagents and equipment used TLC-1 (chloroform), TLC-2 (hexane: ethyl acetate = 8: 2), TLC-3 (chloroform: methanol = 1: 1) 1; Sephadex LH20 (Pharmacia) Silica gel: Kieselgel 60 (70-230 mesh) Merck; Melting point measurement: Yanagimoto melting point meter, 1 HNMRJEOL PMX 60; MS
Measurement: Shimadzu mass spectrometer GCMS-6020, IR measurement: Shimadzu IR-
420, UV measurement: Shimadzu spectrophotometer UV-260.
（Ｂ）構造式 下式で示される通り、フェナントレン環のＣ環にフラ
ン環が共軛したフラノフェナントレンキノンであって、
正規の化学名は、1,6−ジメチルフェナントロ［1,2−
ｂ］フラン−10,11−ジオンである。参考までに、同時
に単離されたタンシノンII、ジヒドロタンシノン及びク
リプトタンシノンの化学構造式を併せて並記する。(B) Structural Formula As shown by the following formula, a furanophenanthrenequinone in which a C ring of a phenanthrene ring and a furan ring coexist,
The canonical chemical name is 1,6-dimethylphenanthro [1,2-
b] Furan-10,11-dione. For reference, the chemical structural formulas of tanshinone II, dihydrotanshinone, and cryptotanshinone that are simultaneously isolated are also shown together.
（Ｃ）物理・化学的性状 色：橙赤色結晶 融点:235〜237℃ 分子式：C18H12O3 紫外部吸収:UVλmax（nm）（log ε）:247.7（3.6
6）,325.3（3.30）,421.3（3.00）． 1592,1430,1190,1170,910,830,790,760. マススペクトル:MS m/z:276（M+）,248（M+‐CO）178,1
65,152. 核磁気共鳴スペクトル：1HNMR（CDCl3）δ:2.32（3H,s,
C1‐CH3）,2.80（3H,s,6-CH3）,7.30-8.00（（4H,C
2,5,7,8‐Ｈ）,8.30（1H,m,C4‐Ｈ）,9.30（1H.m,C9‐
Ｈ）． ［低酸素化心筋モデルに対するタンシノンＩの作用］ （１） 実験方法 実験には、ラット（ウィスター系、♂、体重150〜200
g）の摘出心臓を用い、ランゲンドルフ（Langendorff）
法により灌流し、搏動状態を維持させた。灌流液にはク
レブス−ヘンセライト（Krebs-Henseleit）液（1.20mM
KH2PO4,1.25mM CaCl2,1.20mM MgSO4,4.80mM KCl,120mM
NaCl,2.5mM NaHCO3）に、11mMのグルコースを添加し、9
5％酸素及び５％二酸化炭素を、又は11mMのマンニトー
ルを添加し、95％窒素及び５％二酸化炭素を夫々飽和さ
せたものを使用した。予備灌流及び再酸素化には前者の
液を、低酸素負荷には後者の液を、夫々使用した。摘出
心臓は7ml/分の条件で灌流し、270心拍／分の割合で駆
動させた。心収縮力、灌流圧等のパラメーターは日本光
電製ポリグラフにより記録した。 (C) Physical / Chemical properties Color: Orange red crystal Melting point: 235-237 ° C Molecular formula: C 18 H 12 O 3 Ultraviolet absorption: UVλ max (nm) (log ε): 247.7 (3.6
6), 325.3 (3.30), 421.3 (3.00). 1592,1430,1190,1170,910,830,790,760. Mass spectrum: MS m / z: 276 (M + ), 248 (M + -CO) 178,1
65,152. Nuclear magnetic resonance spectrum: 1 HNMR (CDCl 3 ) δ: 2.32 (3H, s,
C 1- CH 3 ), 2.80 (3H, s, 6-CH 3 ), 7.30-8.00 ((4H, C
2,5,7,8 -H), 8.30 (1H, m, C 4 -H), 9.30 (1H.m, C 9 -
H). [Effect of tanshinone I on hypoxic myocardial model] (1) Experimental method Rats (Wistar strain, ♂, body weight 150-200) were used for the experiment.
g) Using the isolated heart, Langendorff
Was perfused by the method to maintain the beating state. For the perfusate, Krebs-Henseleit solution (1.20 mM
KH 2 PO 4 , 1.25 mM CaCl 2 , 1.20 mM MgSO 4 , 4.80 mM KCl, 120 mM
NaCl, 2.5 mM NaHCO 3 ) and 11 mM glucose added to
5% oxygen and 5% carbon dioxide or 11 mM mannitol were added and saturated with 95% nitrogen and 5% carbon dioxide, respectively. The former solution was used for preperfusion and reoxygenation, and the latter solution was used for low oxygen loading. The isolated heart was perfused under the condition of 7 ml / min and driven at a rate of 270 heartbeats / min. Parameters such as cardiac contractility and perfusion pressure were recorded on a Nihon Kohden polygraph.
被検薬剤の投与法：各薬剤（1.80×10-4Ｍ〜10
-3Ｍ）を10〜106倍に希釈し、これらの希釈液を30〜100
μｌづつ灌流液中に投与した。なお、薬剤は10〜50％の
プロピレングリコールに溶かし、これを更に水で希釈し
た。投与にはインヒュージョンポンプ（テルモ製モデル
STC521）を用い、0,1ml/分の割合で灌流液中へ投与し
た。Administration method of test drug: Each drug (1.80 × 10 -4 M ~ 10
The -3 M) was diluted to 10 to 10 6 times, these dilutions 30-100
Each μl was administered into the perfusate. The drug was dissolved in 10 to 50% propylene glycol and further diluted with water. Infusion pump (Terumo model)
STC521) was used to administer into the perfusate at a rate of 0.1 ml / min.
低酸素負荷及び再酸素化法：摘出心臓への低酸素負
荷は、上記マンニトール加、95％窒素及び５％二酸化炭
素飽和クレブス−ヘンゼライト液を15分間灌流して行っ
た。また再酸素化による心機能回復操作は45分間実施し
た。Hypoxia load and reoxygenation method: Hypoxia load to the isolated heart was performed by perfusing the above-mentioned mannitol-added solution with Krebs-Henseleit solution saturated with 95% nitrogen and 5% carbon dioxide for 15 minutes. Cardiac function recovery by reoxygenation was performed for 45 minutes.
モニタリング：低酸素負荷及び再酸素化時には、心臓
の収縮力、静止張力及び冠灌流圧を連続記録した。ま
た、心筋細胞透過性亢進の指標として、心筋組織からの
ATP代謝産物の遊離状態を把握するため、心臓からの流
出液を経時的に採取し、250nmにおける吸光度を分光光
度計を用いて測定した。Monitoring: During hypoxia and reoxygenation, cardiac contractile force, resting tension and coronary perfusion pressure were continuously recorded. In addition, as an index of increased cardiomyocyte permeability,
To understand the free state of ATP metabolites, the effluent from the heart was collected over time and the absorbance at 250 nm was measured using a spectrophotometer.
（２） タンシノンＩの薬理作用 （Ａ）摘出灌流心臓への薬剤の直接作用 タンシノンIIは4.25ピコモル、ジヒドロタンシノンは
18.0フェムトモル、ヘキサン抽出画分（第７図参照）に
は55.0ピコモルで強い冠血管収縮作用が観察された（第
２図〜第４図参照）。低酸素負荷時の心臓には、冠血管
拡張により心筋への酸素及びエネルギー供給量を代償的
に増加させようとする性質があるので、この自律作用に
反して冠血管収縮作用を起こす上記二物質は、目的上不
適当であると判断された。なお、両メタノール抽出画分
（Ｍ−１及びＭ−２）は何れも明確な対心臓薬理作用を
示さなかった（第５図参照）。(2) Pharmacological action of tanshinone I (A) Direct action of drug on isolated perfused heart Tanshinone II is 4.25 pmol, dihydrotanshinone is
A strong coronary vasoconstrictor action was observed at 55.0 picomoles in the 18.0 femtomolar and hexane extracted fractions (see FIG. 7) (see FIGS. 2 to 4). Since the heart under low oxygen load has the property of compensatingly increasing the oxygen and energy supply to the myocardium by coronary vasodilation, the above-mentioned two substances that cause coronary vasoconstriction in contrast to this autonomic effect. Was judged to be inappropriate for the purpose. Both methanol-extracted fractions (M-1 and M-2) did not show a clear pharmacological effect on the heart (see FIG. 5).
（Ｂ）低酸素負荷心臓に対する薬理作用 摘出灌流心臓に低酸素負荷をかけると、負荷をかけた
直後より心収縮力が速やかに減少すると同時に、静止張
力が上昇し始め、そして心収縮力の消失後、静止張力及
び灌流圧の急激な上昇が観察された。再酸素化により灌
流圧は低酸素負荷前のレベルに戻る傾向があるが、心収
縮力及び静止張力は再酸素化45分後でも殆ど回復せず、
心機能は停止したままとなる。この病態モデルでは、再
酸素化45分後の心収縮力は、初期値の16.6％、灌流圧
は、同じく205.6％、静止張力は、同じく146.7％であっ
た。また、低酸素負荷及び再酸素化期間中における心筋
組織からのATP代謝産物遊離量（イノシン量として換
算）は、1314ナノモル／グラム湿心筋量であった（夫々
の値は四例の平均値）。(B) Pharmacological effect on hypoxia-loaded heart When a hypoxic load is applied to the isolated perfused heart, the systolic force immediately decreases immediately after the stress is applied, at the same time the resting tension starts to rise, and the systolic force disappears. After that, a rapid increase in resting tension and perfusion pressure was observed. Reoxygenation tends to return perfusion pressure to pre-hypoxic levels, but systolic and resting tensions do not recover much after 45 minutes of reoxygenation,
The heart function remains stopped. In this pathological model, the systolic force 45 minutes after reoxygenation was 16.6% of the initial value, the perfusion pressure was 205.6%, and the resting tension was 146.7%. In addition, the amount of ATP metabolite released from myocardial tissue (calculated as the amount of inosine) during the hypoxic load and reoxygenation period was 1314 nmol / g wet myocardial volume (each value is the average of four cases). .
ところがタンシノンＩを低酸素化と同時に灌流液中に
添加すると、第６図及び第７図（四例の平均値）に示す
ように、7.23ピコモル／分の連続注入で心筋力の有意な
回復が見られ、これは本薬剤の低酸素負荷時における心
筋保護作用を示すものと解される。However, when tanshinone I was added to the perfusate at the same time as hypoxia, a continuous infusion of 7.23 pmol / min resulted in a significant recovery of myocardial strength, as shown in FIGS. 6 and 7 (mean value of 4 cases). This is seen, and it is considered that this drug exhibits a myocardial protective action during hypoxic loading.
即ち、タンシノンＩは、7.23ピコモル／分の連続注入
により心収縮力を33％回復させ（第６図）、かつ灌流液
中へのATP代謝物遊離を無投与の場合に比較して有意に
抑制した（第７図）。但し、静止張力上昇度合いや灌流
圧の上昇抑制は認められなかった。That is, tanshinone I restored the systolic force by 33% by continuous infusion of 7.23 pmol / min (Fig. 6), and significantly suppressed the release of ATP metabolites into the perfusate compared with the case of no administration. (Fig. 7). However, neither the increase in resting tension nor the suppression of increase in perfusion pressure was observed.
低酸素負荷による心筋細胞障害の大きさは、灌流液中
にATP代謝産物の量により推測されることが竹尾らによ
り報告されている（S.Takeo and M.Sakanishi,J.Mol.Ce
ll Cardiol.15,577-594,1983）。恐らく、タンシノンＩ
は、低酸素負荷時に細胞膜に直接作用することにより、
ATP再生に必要な基質の遊離を抑制し、これにより再酸
素化時における心筋のエネルギー産生を促進する作用を
奏するのであろう。It has been reported by Takeo et al. That the magnitude of hypoxia-induced cardiomyocyte damage is estimated by the amount of ATP metabolites in the perfusate (S. Takeo and M. Sakanishi, J. Mol. Ce.
ll Cardiol.15,577-594,1983). Probably Tanshinone I
By directly acting on the cell membrane during hypoxia,
It may suppress the release of the substrate required for ATP regeneration, and thereby promote the myocardial energy production during reoxygenation.
（Ｃ）結論 以上の実験事実から、本発明の薬剤は、冠動脈血管の
慢性的な狭窄又は急激な攣縮による虚血状態に対し、予
防、治療乃至救急的効果を奏する薬剤として効果が期待
される。投与方法としては、動脈内への注射乃至静脈へ
の点滴が適当である。(C) Conclusion From the above experimental facts, the drug of the present invention is expected to be effective as a drug having a prophylactic, therapeutic or rescue effect against ischemic conditions due to chronic stenosis or rapid spasm of coronary artery blood vessels. . As an administration method, injection into an artery or infusion into a vein are appropriate.
（実施例） 日本薬局方製剤総則注射剤の項（A-107）に準じて２
％のタンシノンＩを含む10ml入り注射用及び20ml入り点
滴用各薬剤を調製した。(Example) In accordance with the Japanese Pharmacopoeia General Rules for Injection (A-107) 2
10 ml injections and 20 ml infusions containing% tanshinone I were prepared.
以上の薬剤は、通常、注射用の場合は虚血性疾患に対
し一回１筒を静脈内に、点滴用の場合は１〜２筒を輸液
中に混ぜて投与する。The above drugs are usually administered by injecting one cylinder once for an ischemic disease in the case of injection, and mixing one or two cylinders in the case of infusion during infusion.
（発明の効果） 以上説明したように、本発明は、これまで漢方における
理血薬（血行改善剤）として、伝統的に狭心症、心筋梗
塞の治療に利用されて来たとは言いながら、その薬理的
評価が不明であった丹参の有効成分を解明し、かつその
有毒成分を除いた薬効成分のみの臨床的応用を可能なら
しめたことにより、人類の健康維持乃至増進に寄与しう
る。(Effects of the Invention) As described above, the present invention has been traditionally used for the treatment of angina pectoris and myocardial infarction as a blood-treatment drug (blood circulation-improving agent) in Kampo, By elucidating the active ingredient of Danshen whose pharmacological evaluation was unknown and enabling clinical application of only the medicinal ingredient excluding its toxic ingredient, it can contribute to the maintenance or promotion of human health.
【図面の簡単な説明】 第１図は、タンシノンＩ及びその関連物質の製造工程の
一例を示す工程図、第２図は、タンシノンIIの濃度対灌
流圧及び心筋収縮力の相関を示すグラフ、第３図は、ジ
ヒドロタンシノンの第２図と同様のグラフ、第４図は、
ヘキサン抽出画分の第２図と同様のグラフ、第５図はＭ
−１及びＭ−２画分の濃度と心筋収縮力回復の関係を示
すグラフ、第６図は、タンシノンＩの心筋収縮力回復作
用を示すグラフ、第７図は、タンシノンＩによるATP代
謝産物の遊離抑制作用を示すグラフである。BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a process diagram showing an example of a process for producing tanshinone I and its related substances, and FIG. 2 is a graph showing the correlation between tanshinone II concentration versus perfusion pressure and myocardial contractile force. FIG. 3 is a graph similar to FIG. 2 for dihydrotanshinone, and FIG. 4 is
A graph similar to Fig. 2 of the hexane extracted fraction, and Fig. 5 shows M
-1 and a graph showing the relationship between the concentrations of M-2 fraction and myocardial contractile force recovery, Fig. 6 is a graph showing the myocardial contractile force recovery action of tanshinone I, and Fig. 7 shows the ATP metabolites of tanshinone I. It is a graph which shows a release suppression effect.
Claims (1)
とする虚血性疾患治療剤。1. A therapeutic agent for ischemic disease containing Tanshinone I as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62102583A JPH0830077B2 (en) | 1987-04-24 | 1987-04-24 | Ischemic disease therapeutic agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62102583A JPH0830077B2 (en) | 1987-04-24 | 1987-04-24 | Ischemic disease therapeutic agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63267798A JPS63267798A (en) | 1988-11-04 |
| JPH0830077B2 true JPH0830077B2 (en) | 1996-03-27 |
Family
ID=14331251
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62102583A Expired - Fee Related JPH0830077B2 (en) | 1987-04-24 | 1987-04-24 | Ischemic disease therapeutic agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0830077B2 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20000027306A (en) * | 1998-10-28 | 2000-05-15 | 황규언 | Medicinal composition for treating hepatitis b |
| US6589572B2 (en) * | 2001-06-14 | 2003-07-08 | Medvill Co., Ltd. | Hypertension-treatment and cholesterol-depressant composition comprising extract from mixture of Panax notoginseng and Salvia miltiorrhiza and method of preparing the same |
| KR20030091465A (en) * | 2002-05-28 | 2003-12-03 | 학교법인 경희대학교 | Composition comprising an extract of Salviae Miltiorrhizae BGE having neuro-protective activity |
| US20040191334A1 (en) * | 2003-03-24 | 2004-09-30 | Pang-Chui Shaw | Use of transhinone derivates as cholinesterase inhibitors in treating related diseases |
| KR100687246B1 (en) | 2005-06-15 | 2007-02-26 | 원광대학교산학협력단 | Composition comprising Tanshinone? for treating and preventing liver disease |
| CN101394860B (en) * | 2006-01-13 | 2013-05-29 | 范斯坦医药研究院 | Inhibition of inflammatory cytokine production with tanshinones |
| GB201421479D0 (en) * | 2014-12-03 | 2015-01-14 | Phynova Ltd | A plant extract and compounds for use in wound healing |
| CN107158347A (en) * | 2017-06-12 | 2017-09-15 | 北京京师脑力科技有限公司 | A kind of pharmaceutical composition and preparation method and purposes for treating heart disease |
-
1987
- 1987-04-24 JP JP62102583A patent/JPH0830077B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPS63267798A (en) | 1988-11-04 |
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