JPH0212449B2 - - Google Patents
Info
- Publication number
- JPH0212449B2 JPH0212449B2 JP15917582A JP15917582A JPH0212449B2 JP H0212449 B2 JPH0212449 B2 JP H0212449B2 JP 15917582 A JP15917582 A JP 15917582A JP 15917582 A JP15917582 A JP 15917582A JP H0212449 B2 JPH0212449 B2 JP H0212449B2
- Authority
- JP
- Japan
- Prior art keywords
- cholesterol
- prosapogenin
- ginseng
- arteriosclerosis
- carrot
- 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
Links
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000003524 antilipemic agent Substances 0.000 claims description 3
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 22
- 235000012000 cholesterol Nutrition 0.000 description 10
- 240000004371 Panax ginseng Species 0.000 description 6
- 235000008434 ginseng Nutrition 0.000 description 6
- 150000007949 saponins Chemical class 0.000 description 6
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 5
- 235000003140 Panax quinquefolius Nutrition 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 229930182490 saponin Natural products 0.000 description 5
- 235000017709 saponins Nutrition 0.000 description 5
- 206010003210 Arteriosclerosis Diseases 0.000 description 3
- 244000000626 Daucus carota Species 0.000 description 3
- 235000002767 Daucus carota Nutrition 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- YDQIRODFTJGGMP-UHFFFAOYSA-N Prosapogenin Chemical compound C12CC(C)(C)CCC2(C(=O)OC2C(C(O)C(O)C(CO)O2)O)CCC(C2(CCC34)C)(CO)C1=CCC2C3(C)CC(O)C(O)C4(C)C(=O)OC1OC(CO)C(O)C(O)C1O YDQIRODFTJGGMP-UHFFFAOYSA-N 0.000 description 2
- ZNFRITHWVZXJRK-UHFFFAOYSA-N Vitalboside A Natural products C12CC(C)(C)CCC2(C(O)=O)CCC(C2(CCC3C4(C)C)C)(C)C1=CCC2C3(C)CCC4OC1OC(CO)C(O)C(O)C1O ZNFRITHWVZXJRK-UHFFFAOYSA-N 0.000 description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 description 2
- VTXFLUJNMHWAAT-UHFFFAOYSA-N alternoside VII Natural products CC1(C)CC(O)C2(CO)C(O)CC3(C)C(=CCC4C5(C)CCC(OC6OC(C(O)C(OC7OC(CO)C(O)C(O)C7O)C6O)C(=O)O)C(C)(C)C5CCC34C)C2C1 VTXFLUJNMHWAAT-UHFFFAOYSA-N 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 229940099112 cornstarch Drugs 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229930182494 ginsenoside Natural products 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- OILHVNROWDFZDW-UHFFFAOYSA-N prosapogenin Natural products CC1(C)CCC2(C(O)CC3(C)C(=CCC4C5(C)CCC(OC6OC(CO)C(O)C(O)C6O)C(C)(C=O)C5CCC34C)C2C1)C(=O)O OILHVNROWDFZDW-UHFFFAOYSA-N 0.000 description 2
- IAGSHEHQJJTLLR-UHFFFAOYSA-N sapindoside B Natural products OC1C(C)OC(OC2C(OCC(O)C2O)OC2C(C3C(C4C(C5(CCC6(CCC(C)(C)CC6C5=CC4)C(O)=O)C)(C)CC3)(C)CC2)(C)CO)C(O)C1OC1OCC(O)C(O)C1O IAGSHEHQJJTLLR-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- PYXFVCFISTUSOO-HKUCOEKDSA-N (20S)-protopanaxadiol Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@H]([C@@](C)(O)CCC=C(C)C)[C@H]4[C@H](O)C[C@@H]3[C@]21C PYXFVCFISTUSOO-HKUCOEKDSA-N 0.000 description 1
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- 206010065559 Cerebral arteriosclerosis Diseases 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 241000725101 Clea Species 0.000 description 1
- 229930183217 Genin Natural products 0.000 description 1
- 108010023302 HDL Cholesterol Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 238000008214 LDL Cholesterol Methods 0.000 description 1
- 108010028554 LDL Cholesterol Proteins 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
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 235000002789 Panax ginseng Nutrition 0.000 description 1
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
- 206010038372 Renal arteriosclerosis Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 230000001315 anti-hyperlipaemic effect Effects 0.000 description 1
- PYXFVCFISTUSOO-UHFFFAOYSA-N betulafolienetriol Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC(C(C)(O)CCC=C(C)C)C4C(O)CC3C21C PYXFVCFISTUSOO-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000006345 epimerization reaction Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- GZYPWOGIYAIIPV-JBDTYSNRSA-N ginsenoside Rb1 Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)O[C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)CC[C@]4(C)[C@H]3C[C@H]2O)C)(C)CC1)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GZYPWOGIYAIIPV-JBDTYSNRSA-N 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 201000005851 intracranial arteriosclerosis Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- SWQINCWATANGKN-UHFFFAOYSA-N protopanaxadiol Natural products CC(CCC=C(C)C)C1CCC2(C)C1C(O)CC1C3(C)CCC(O)C(C)(C)C3CCC21C SWQINCWATANGKN-UHFFFAOYSA-N 0.000 description 1
- 230000000384 rearing effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
Description
本発明はニンジン―C20―プロサポゲニンを有
効成分とする抗高脂血症剤に関する。
本発明の有効成分であるニンジン―C20―プロ
サポゲニンは薬用人参（Panax ginseng C.A.
Meyerの根部）に含まれる各種サポニンのうちジ
ンセノサイドRb1，Rb2，Rb3，Rc，Rdを酸加水
分解してC20位のグリコシド結合を開裂すること
によつて得られるものである。
この酸加水分解ではエピメリ化が生起し、２種
の立体異性体C20R―およびC20S―体が生成す
る。C20R―プロサポゲニンおよびC20S―プロサ
ポゲニンはニンジンサポニンの酸加水分解反応系
のなかから本発明者等によつて単離され、化学構
造が確認されたもので、勿論天然には存在しない
ものである。［アルツナイミツテル フオルシユ
ンク第30巻936頁1980年（Arzneim Forsch.30，
936（1980））］
従来、薬用人参には多岐にわたる薬理作用が知
られている。また、最近薬用人参の各種成分が分
離され漸次薬効との関係が解明されつつある。本
発明者等に、先に各種のニンジンサポニン成分を
純粋に単離し、ジンセノサイドRb1についてコレ
ステロール低下作用（抗高脂血作用）を有するこ
とを見出した（日本薬学会第102年会（1982））。
しかし単離されるニンジンサポニンの全てにかゝ
る薬理作用が認められるわけではなく、化学構造
と薬理作用との関係もほとんど解明されていな
い。
本発明者等は、今回ニンジンサポニンのうちジ
ンセノサイドRb1，Rb2，Rb3，Rc，Rd（C20S―
プロトパナキサジオールをゲニンとするサポニン
群）のC20位の糖鎖が解裂されて生じたC20―プ
ロサポゲニンに顕著な血中コレステロール低下作
用を認めたものである。
ニンジンサポニンの糖鎖が部分的に開裂された
プロサポゲニンで、殊に天然に存在しないC20R
型異性体の薬理作用は全く予想外のことである。
本発明で使用されるプロサポゲニンの上記薬理
作用を調べる方法としては、ラツトの血清中のコ
レステロール含量を測定する方法が採用される。
以下測定結果を試験方法とともに示す。
実験１ 高脂食飼育ラツトの血清コレステロール
濃度上昇抑制試験
Wistar系雄ラツト（体重100ｇ前後）を用い、
固型飼料（日本クレア製CE―２）で予備飼育後、
実験飼料はCE―２粉末飼料にコレステロールと
コール酸をそれぞれ1.0％、0.5％添加した食餌
（１％コレステロール食）で、毎日定時に与え、
自由摂取として６日間飼育した。ニンジン―
C20R―プロサポゲニンはコレステロール食飼育
期間中の後半３日間に腹控内投与した。飼育室は
恒温恒湿（25℃、相対湿度60％）に保ち、12時間
毎の明暗サイクルとした。最終投与した20時間後
に頚動脈より採血し、冷却遠心分離により血清を
得た。血清中の総コレステロールはcholesterol
Ｂ―Test wako、遊離コレステロールは遊離コ
レステロール測定用cholesterol―Test wako補
助試薬で遊離コレステロールを沈澱分離後
cholesterol Ｂ―Test wakoを用いて比色定量し
た。LDL―コレステロールとHDL―コレステロ
ールは野間らの方法〔クリニカルケミストリー第
24巻1504頁1978年、同書第25巻1480頁1979年
（A.Noma et al.Clin.Chem.，24，1504（1978），
ibid.25，1480（1979））〕で定量した。
The present invention relates to an antihyperlipidemic agent containing ginseng-C20-prosapogenin as an active ingredient. Ginseng-C20-prosapogenin, the active ingredient of the present invention, is derived from medicinal ginseng (Panax ginseng CA).
It is obtained by acid hydrolyzing ginsenosides Rb 1 , Rb 2 , Rb 3 , Rc, and Rd among various saponins contained in Meyer's root (Meyer's root) to cleave the glycosidic bond at the C20 position. This acid hydrolysis causes epimerization, producing two stereoisomers, C20R- and C20S-. C20R-prosapogenin and C20S-prosapogenin were isolated by the present inventors from the acid hydrolysis reaction system of carrot saponin, and their chemical structures were confirmed, and of course they do not exist in nature. [Arzneim Forsch. 30, vol. 30 , p. 936, 1980.
936 (1980))] Medicinal ginseng has been known to have a wide variety of pharmacological actions. In addition, various components of medicinal ginseng have been recently isolated, and their relationship with medicinal efficacy is gradually being clarified. The present inventors previously isolated various ginseng saponin components and discovered that ginsenoside Rb 1 has a cholesterol-lowering effect (antihyperlipidemic effect) (102nd Annual Meeting of the Pharmaceutical Society of Japan (1982)) ).
However, not all isolated ginseng saponins have such pharmacological effects, and the relationship between chemical structure and pharmacological effects is also poorly understood. The present inventors have investigated the effects of ginsenosides Rb 1 , Rb 2 , Rb 3 , Rc, and Rd (C20S-
C20-prosapogenin, which is produced by the cleavage of the sugar chain at the C20 position of the saponin group whose genin is protopanaxadiol, has been found to have a significant blood cholesterol-lowering effect. Prosapogenin is a partially cleaved sugar chain of carrot saponin, especially C20R, which does not exist in nature.
The pharmacological effects of the type isomers are completely unexpected. As a method for examining the above-mentioned pharmacological action of prosapogenin used in the present invention, a method of measuring cholesterol content in rat serum is employed.
The measurement results are shown below along with the test method. Experiment 1 Test for suppressing increase in serum cholesterol concentration in rats fed a high-fat diet Using Wistar male rats (body weight around 100 g),
After preliminary rearing on solid feed (CE-2 manufactured by Clea Japan),
The experimental feed was a CE-2 powdered feed supplemented with 1.0% and 0.5% cholesterol and cholic acid (1% cholesterol diet), which was given at a fixed time every day.
The animals were kept for 6 days with free access. carrot-
C20R-prosapogenin was administered intraperitoneally during the latter three days of the cholesterol diet feeding period. The breeding room was kept at constant temperature and humidity (25°C, relative humidity 60%) with a 12-hour light/dark cycle. Blood was collected from the carotid artery 20 hours after the final administration, and serum was obtained by cold centrifugation. Total cholesterol in serum is cholesterol
B-Test wako, free cholesterol is precipitated and separated using cholesterol-Test wako auxiliary reagent for measuring free cholesterol.
Colorimetric determination was performed using cholesterol B-Test wako. LDL-cholesterol and HDL-cholesterol were measured using the method of Noma et al. [Clinical Chemistry Vol.
Volume 24, page 1504, 1978, Volume 25, page 1480, 1979 (A.Noma et al.Clin.Chem., 24 , 1504 (1978),
ibid. 25 , 1480 (1979)].
【表】
実験２ 急性毒性試験
ニンジン―C20R―プロサポゲニンを生理食塩
液に懸濁しICR系マウス（７週令 雄）３匹に
500mg／Kg腹控内投与し、７日間観察したが死亡
例はなかつた。
以上の実験から明らかなように、ニンジンサポ
ニン―C20R―プロサポゲニンの投与により、血
清中のコレステロールの増加が顕著に抑制され
る。したがつて本剤の投与は高コレステロール症
など高脂血症の改善に有効であり、動脈硬化の予
防と治療上有用である。
コレステロール（脂質）の血中濃度の増加は動
脈硬化症の重要な発症原因であることはすでに定
説であり、冠状動脈硬化症、脳動脈硬化症、腎動
脈硬化症、末梢動脈硬化症など重篤な病状への予
防、ならびに治療のために本剤の投与は有用であ
る。
本発明で用いられるC20―プロサポゲニンは、
それ自体あるいは、適宜製剤用の担体、賦形剤希
釈剤と混合し、粉末、顆粒、錠剤、カプセル、注
射剤などの形態で経口的または非経口的に投与す
ることができる。
投与量は、たとえば成人の場合は、１日30〜
1000mg、好ましくは50〜300mgを１〜３回に分け
て内服、注射するが、年齢、体重、症状により、
投与量が増減されることはいうまでもない。
つぎに、本発明の抗高脂血症剤を経口投与する
際の細粒の調製例を記す。
ニンジン―C20R―プロサポゲニン100mg、乳糖
616mgおよびコーンスターチ264mgを均一に混和
し、これに10％ハイドロキシプロピルセルロース
（HPC）水溶液を糊剤として、日本薬局方製剤総
則顆粒剤の項に準じて顆粒剤を製す。[Table] Experiment 2 Acute toxicity test Carrot-C20R-prosapogenin was suspended in physiological saline and administered to three ICR mice (7 weeks old, male).
500mg/Kg was administered intraperitoneally and observed for 7 days, but there were no deaths. As is clear from the above experiments, administration of carrot saponin-C20R-prosapogenin significantly suppresses the increase in serum cholesterol. Therefore, administration of this drug is effective in improving hyperlipidemia such as hypercholesterolemia, and is useful in preventing and treating arteriosclerosis. It is already well-established that an increase in the blood concentration of cholesterol (lipids) is an important cause of arteriosclerosis, and it is believed to be an important cause of arteriosclerosis, which can lead to serious diseases such as coronary arteriosclerosis, cerebral arteriosclerosis, renal arteriosclerosis, and peripheral arteriosclerosis. Administration of this drug is useful for the prevention and treatment of various medical conditions. C20-prosapogenin used in the present invention is
It can be administered orally or parenterally by itself or mixed with appropriate pharmaceutical carriers, excipients, and diluents in the form of powder, granules, tablets, capsules, injections, and the like. For adults, the dosage is, for example, 30 to 30 mg per day.
1000mg, preferably 50 to 300mg, is administered orally or injected in 1 to 3 doses, depending on age, weight, and symptoms.
Needless to say, the dose may be increased or decreased. Next, an example of preparing fine particles for oral administration of the antihyperlipidemic agent of the present invention will be described. Carrot-C20R-prosapogenin 100mg, lactose
616 mg of cornstarch and 264 mg of corn starch are mixed uniformly, and a 10% aqueous hydroxypropyl cellulose (HPC) solution is used as a sizing agent to prepare granules according to the Japanese Pharmacopoeia General Rules for Preparations Granules section.
Claims (1)
とする抗高脂血症剤。1. An antihyperlipidemic agent containing ginseng-C20-prosapogenin as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15917582A JPS5948421A (en) | 1982-09-13 | 1982-09-13 | Antilipemic agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15917582A JPS5948421A (en) | 1982-09-13 | 1982-09-13 | Antilipemic agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5948421A JPS5948421A (en) | 1984-03-19 |
| JPH0212449B2 true JPH0212449B2 (en) | 1990-03-20 |
Family
ID=15687929
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15917582A Granted JPS5948421A (en) | 1982-09-13 | 1982-09-13 | Antilipemic agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5948421A (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61109155A (en) * | 1984-11-01 | 1986-05-27 | Mitsubishi Electric Corp | Parity detecting circuit |
| JP2002322068A (en) * | 2001-02-26 | 2002-11-08 | Japan Science & Technology Corp | Vascular regeneration promoter |
| DE10154221A1 (en) * | 2001-11-07 | 2003-05-15 | Max Delbrueck Centrum | Agent for the treatment of lesions of the nervous system |
| JP5546851B2 (en) | 2009-12-21 | 2014-07-09 | ライオン株式会社 | Anemia ameliorating agent and anemia ameliorating composition |
-
1982
- 1982-09-13 JP JP15917582A patent/JPS5948421A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5948421A (en) | 1984-03-19 |
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