JPS63154624A - Remedy for jaundice - Google Patents
Remedy for jaundiceInfo
- Publication number
- JPS63154624A JPS63154624A JP30250486A JP30250486A JPS63154624A JP S63154624 A JPS63154624 A JP S63154624A JP 30250486 A JP30250486 A JP 30250486A JP 30250486 A JP30250486 A JP 30250486A JP S63154624 A JPS63154624 A JP S63154624A
- Authority
- JP
- Japan
- Prior art keywords
- bucladesine
- liver
- jaundice
- increased
- administration
- 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.)
- Granted
Links
- 206010023126 Jaundice Diseases 0.000 title claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 8
- 239000004480 active ingredient Substances 0.000 claims abstract description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 229960005263 bucladesine Drugs 0.000 abstract description 14
- 208000019423 liver disease Diseases 0.000 abstract description 5
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 abstract description 4
- 210000004369 blood Anatomy 0.000 abstract description 3
- 239000008280 blood Substances 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000000843 powder Substances 0.000 abstract description 3
- 239000000243 solution Substances 0.000 abstract description 3
- 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 abstract description 2
- 208000019425 cirrhosis of liver Diseases 0.000 abstract description 2
- 230000029142 excretion Effects 0.000 abstract description 2
- 239000008103 glucose Substances 0.000 abstract description 2
- 230000002440 hepatic effect Effects 0.000 abstract description 2
- 208000006454 hepatitis Diseases 0.000 abstract description 2
- 231100000283 hepatitis Toxicity 0.000 abstract description 2
- 238000000034 method Methods 0.000 abstract description 2
- 230000001603 reducing effect Effects 0.000 abstract description 2
- CJGYSWNGNKCJSB-YVLZZHOMSA-N bucladesine Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](OC(=O)CCC)[C@@H]2N1C(N=CN=C2NC(=O)CCC)=C2N=C1 CJGYSWNGNKCJSB-YVLZZHOMSA-N 0.000 abstract 4
- 210000005229 liver cell Anatomy 0.000 abstract 1
- 239000008354 sodium chloride injection Substances 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 210000003462 vein Anatomy 0.000 abstract 1
- KRBZRVBLIUDQNG-JBVYASIDSA-M Bucladesine sodium Chemical compound [Na+].C([C@H]1O2)OP([O-])(=O)O[C@H]1[C@@H](OC(=O)CCC)[C@@H]2N1C(N=CN=C2NC(=O)CCC)=C2N=C1 KRBZRVBLIUDQNG-JBVYASIDSA-M 0.000 description 11
- 238000001356 surgical procedure Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 4
- 230000000740 bleeding effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 230000000241 respiratory effect Effects 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 206010067125 Liver injury Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 231100000234 hepatic damage Toxicity 0.000 description 2
- 230000008818 liver damage Effects 0.000 description 2
- 230000005976 liver dysfunction Effects 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 201000001231 mediastinitis Diseases 0.000 description 2
- 235000003715 nutritional status Nutrition 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 210000000115 thoracic cavity Anatomy 0.000 description 2
- 102000003914 Cholinesterases Human genes 0.000 description 1
- 108090000322 Cholinesterases Proteins 0.000 description 1
- 206010009192 Circulatory collapse Diseases 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000588772 Morganella morganii Species 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 208000003734 Supraventricular Tachycardia Diseases 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000003872 anastomosis Effects 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940048961 cholinesterase Drugs 0.000 description 1
- 229960004912 cilastatin Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000013110 gastrectomy Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 206010047302 ventricular tachycardia Diseases 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 238000004383 yellowing Methods 0.000 description 1
Landscapes
- Saccharide Compounds (AREA)
- 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〕 本発明は新規な黄疸治療剤に関する。[Detailed description of the invention] [Industrial application field] The present invention relates to a novel therapeutic agent for jaundice.
黄疸は肝炎、術後肝障害、肝硬変及び薬剤性肝障害等に
伴って発生する。Jaundice occurs with hepatitis, postoperative liver damage, liver cirrhosis, drug-induced liver damage, etc.
しかし、これまでに、黄疸の治療に優れた効果を示す薬
剤はなく、その開発が望まれていた。However, until now, there has been no drug that has been shown to be highly effective in treating jaundice, and the development of one has been desired.
斯かる実状において、本発明者は鋭意研究を行った結果
、Ｎ’、２’−０−シブチリルアデノシン−３７、Ｓ／
−サイクリックホスフェート（以下、「ブクラデシン」
と称する）が優れた黄疸治療効果を有することを見出し
、本発明を完成した。Under such circumstances, the present inventor conducted intensive research and found that N',2'-0-sibutyryl adenosine-37, S/
−Cyclic phosphate (hereinafter referred to as “bucladesine”)
The present invention has been completed based on the discovery that the compound (referred to as ``2000'') has an excellent therapeutic effect on jaundice.
すなわち、本発明は、ブクラデシン又はその塩を有効成
分として含有する黄疸治療剤を提供するものである。That is, the present invention provides a therapeutic agent for jaundice containing bucladesine or a salt thereof as an active ingredient.
ブクラデシンは、すでに公知の化合物で、そのナトリウ
ム塩は商品名「アクトシン」なる名称にて急性循環不全
の治療剤として上布されている〔医学のあゆみ１２３．
１０９９〜１１１４ （１９８２）、ファルマシア２１
（７） ６５７〜６６１ （１９８５）、製造法：特公
昭５２−１６１１９号、特公昭５２−８３７４号、特公
昭６０−２４１１８号、特公昭６゜−２４１１９号、特
公昭６０−３５３５４号および特公昭６０−３５３５５
号公報参照〕。Bucladesine is already a well-known compound, and its sodium salt has been marketed as a therapeutic agent for acute circulatory failure under the trade name "Actosin" [Medical History 123.
1099-1114 (1982), Pharmacia 21
(7) 657-661 (1985), manufacturing method: Special Publication No. 52-16119, Special Publication No. 52-8374, Special Publication No. 60-24118, Special Publication No. 60-24119, Special Publication No. 60-35354, and Special Publication No. 60-35354. Kosho 60-35355
Please refer to the publication].
ブクラデシンナトリウムの静脈投与による急性毒性（Ｌ
Ｄ５０ ）は、マウｘ５４５ｍｇ／ｋｉｐ、ラツ）４５
９１ｒＬｇ／に９と低いので、広い範囲の投与量で使用
することができる。Acute toxicity due to intravenous administration of bucladesine sodium (L
D50) is mouse x 545 mg/kip, rat) 45
Since it is as low as 91 rLg/9, it can be used in a wide range of dosages.
本発明の黄疸治療剤の投与方法としては、例えばブクラ
デシン粉末または凍結乾燥品を生理食塩液、ブドウ糖液
、その他の輸液中に加えて静脈内に投与するのが適当で
ある。投与量としては成人１日当、９１００〜１２００
ｍｇ、通常は３００〜６００ ｍｇが適当であシ、症状
等によシ適宜増減する。従ってその製剤としては、例え
ばブクラデシンナトリウム３００ｍｇ／アンプルの凍結
乾燥品が好ましい。As a method for administering the therapeutic agent for jaundice of the present invention, for example, it is appropriate to add bucladesine powder or a lyophilized product to a physiological saline solution, glucose solution, or other infusion solution and administer it intravenously. The dosage is 9100 to 1200 per day for adults.
mg, usually 300 to 600 mg, and may be increased or decreased as appropriate depending on symptoms, etc. Therefore, the preferred formulation is, for example, a lyophilized product containing 300 mg/ampule of bucladesine sodium.
本発明の黄疸治療剤の作用機序の詳細は必ずしも明らか
でないが、ブクラデシンの投与により肝血流量が増加し
、かつ肝細胞内エネルギーレベルの上昇のためビリルビ
ン排泄能が増加し、減黄に効果があるものと思われる。Although the details of the mechanism of action of the jaundice treatment agent of the present invention are not necessarily clear, administration of bucladesine increases hepatic blood flow and increases bilirubin excretion capacity due to the increase in hepatocyte intracellular energy level, which is effective in reducing yellowing. It seems that there is.
次に実施例を挙げて説明する。 Next, an example will be given and explained.
実施例１
ブクラデシンナトリウム凍結乾燥品３００ｍｇのアンゾ
ルを生理食塩液５ ｍ／に溶解する。Example 1 300 mg of lyophilized bucladesine sodium Anzol was dissolved in 5 m/ml of physiological saline.
これを３００〜５００ｄの生理食塩液に加えて、６〜２
４時間かけて点滴静注する。Add this to 300 to 500 d of physiological saline and add 6 to 2
Administer intravenously over 4 hours.
（１）症例１：５６歳、男性
昭和６０年９月頃よシ啄下困難感が出現し、下部食道癌
の診断を受け、１０月９日に食道全摘胸骨後胃管食道吻
合術を施行された。(1) Case 1: 56-year-old male. Around September 1985, he developed a feeling of difficulty in swallowing, was diagnosed with lower esophageal cancer, and underwent total esophagectomy and retrosternal gastroesophageal anastomosis on October 9. It was done.
術前には肝機能障害はなく、栄養状態は良好で体重減少
もなかった。手術はＮＬＡ麻酔下に行われ、手術時間１
０時間、出血９００＋ｗＪ’に対し、４．Ｑツクの濃厚
赤血球が輸血された。Before surgery, the patient had no liver dysfunction, was in good nutritional status, and had no weight loss. The surgery was performed under NLA anesthesia, and the operation time was 1.
0 hours, bleeding 900+wJ', 4. Qtsuku's concentrated red blood cells were transfused.
術後呼吸管理を目的としてＩＣＵに転科されたが、第２
病日には気管内チューブが抜去され、肺・循環系機能は
良好でらった。第３病日よシ右肺野に異常陰影が出現し
、右胸腔内感染が疑われた。異常陰影は次第に増強し、
胸腔ドレンよ、り Ｍｏｒｇａｎｅｌｌａ Ｍｏｒｇａ
ｎｉｉ菌が検出された。第５病日よシ黄疸が出現し次第
に増強し、第１４病日には、Ｔ、Ｂ１１．１０ ■／ｄ
ｉ 、 Ｄ、Ｂｉｌ、 ７． Ｉ Ｑ／ｄｉ 、 １．
Ｄ、Ｂｊｌ、 ２．９ ｙｒＱ／Ωまで上昇した。第１
５病日よシブクラデシン９００■／日の静脈内投与を開
始したところ、第１７病日よシビリルビン値の低下を認
め、第２７病日にはＴ、Ｂ目、３．ｇａｇ７ｄｌ 、
Ｄ。He was transferred to the ICU for postoperative respiratory management, but the second
On the day of his illness, the endotracheal tube was removed, and his pulmonary and circulatory system functions were good. On the third hospital day, an abnormal shadow appeared in the right lung field, and infection within the right thoracic cavity was suspected. The abnormal shadow gradually strengthens,
Chest cavity drain Morganella Morga
nii bacteria was detected. On the 5th day of illness, jaundice appeared and gradually worsened, and on the 14th day of illness, T, B11.10 ■/d
i, D, Bill, 7. I Q/di, 1.
D, Bjl, increased to 2.9 yrQ/Ω. 1st
Intravenous administration of sibucladesine 900 μ/day was started on the 5th hospital day, and a decrease in sibilirubin levels was observed on the 17th day, and on the 27th day, T, B, and 3. gag7dl,
D.
Ｂｉｌ、 ２．９ ｍｇ／ ｄｌ 、 １．Ｄ、Ｂｉｌ
、 １．０１１１９／ ｄｌまで減少した。肝機能の指
標の一つとされるへ、ｅシラスチンテストも、投与前５
８％から投与中止時の９５％まで上昇した。Bil, 2.9 mg/dl, 1. D. Bill
, decreased to 1.01119/dl. The e-cilastin test, which is considered to be one of the indicators of liver function, also requires
The rate increased from 8% to 95% at the time of discontinuation of administration.
（１１）症例２：６３歳、男性
昭和５８年５月に食道全摘術を施行され、同年８月に放
射線療法を行埴経過観察中であつだが、昭和６０年６月
より縦隔内胃管よυの出血が始まシ、１１月には出血が
大量となり、胃管全摘術、食道疼造設術を施行された。(11) Case 2: A 63-year-old man who underwent total esophagectomy in May 1980, underwent radiotherapy in August of the same year, and was currently under follow-up observation, but since June 1985 he has been diagnosed with a mediastinal gastric tube. The patient started bleeding profusely, and in November, the bleeding became profuse, and a total gastrectomy and esophageal angioplasty were performed.
術前検査テはＴ、ｎ＋ｘ、 １．４ ｍｇ ／ ｄｉ
、 Ａ、ＬＰ ２５７ＩＵ／ｌ 、ＬＤＨ２７４７ＩＵ
／ｌ、ＣｈＥｏ、３０ΔＰＨと肝機能の低下を思わせ、
栄養状態も悪く、Ｔ、Ｐ、 ４．７ ｒ／ｃ＃ 、 Ａ
ＬＢ ２．８５１／ｄｌ。Preoperative test: T, n+x, 1.4 mg/di
, A, LP 257IU/l, LDH2747IU
/l, ChEo, 30ΔPH, suggesting a decline in liver function,
Poor nutritional status, T, P, 4.7 r/c#, A
LB 2.851/dl.
Ｔ、ｅｈｏｌ ８５ ｍｇ／ ｄｌであった。T, ehol was 85 mg/dl.
手術はＮＬＡ麻酔麻酔性われ、手術時間５時間２０分、
出血量２７００ｍ／に対し１２ノＱツクの保存血輸血が
行われた。術後ＩＣＵに２日間入室後、状態も安定して
いたため病棟へ転科したが１手術後９病日までに黄疸が
増強しく Ｔ、 Ｂ目、 ６． ｓ ｍｇ／
ｄｉ 、 Ｄ、Ｄｌｌ、 ３． ９ ｍｇ／ｄ
ｉ 。The surgery was performed under NLA anesthesia, and the operation time was 5 hours and 20 minutes.
For a blood loss of 2,700 m/cm, 12 Qts of preserved blood was transfused. After staying in the ICU for 2 days after surgery, the patient's condition was stable and he was transferred to the hospital ward, but by the 9th hospital day after the first surgery, his jaundice had worsened. smg/
di, D, Dll, 3. 9 mg/d
i.
１、Ｄ、Ｂ１１ 、２．９ ｍｇ ／ ｄｉ ）呼吸状
態も悪化したため、肝機能障害および縦隔炎の疑いにて
ＩＣＵＩ／Ｃ再転科した。転科後、呼吸管理、栄養管理
を開始し、縦隔炎によると思われる上室・心室性頻脈に
対してβ−ブロッカ−を投与した。ＩＣＵ転科後第６病
日にはＴ、Ｂ１１゜１６．５ｍｇ／＃まで上昇し、へ／
ｅシラスチンテストは２０％であった。ブクラデシン６
００■／日の静脈内投与を開始し、第１１病日にはＴ、
Ｂｉｌ、 １１．８１１！ｇ／ ｄｌまで減少し、ヘノ
Ｑシラスチンテストは５９％まで上昇した。1, D, B11, 2.9 mg/di) As his respiratory condition worsened, he was transferred to ICUI/C again on suspicion of liver dysfunction and mediastinitis. After transferring to another hospital, respiratory and nutritional management was started, and β-blocker was administered for supraventricular/ventricular tachycardia, which was thought to be caused by mediastinitis. On the 6th hospital day after being transferred to the ICU, T and B11 levels increased to 16.5 mg/#, and
eCilastin test was 20%. Bucladesine 6
00■/day intravenous administration was started, and on the 11th hospital day, T,
Bill, 11.811! g/dl and the HenoQ cillastin test increased to 59%.
以−ヒの実施例から明らかな如く、ヘノＱシラスチン及
びコリンエステラーゼ値も上昇していることから、ブク
ラデシンは症状としての黄痘の治療に有用であるのみな
らず、肝臓の予備能を改善しているということができ、
肝−８＝
炎等の各種肝疾患の治療にも有用である。As is clear from the examples below, bucladesine is not only useful for the treatment of jaundice as a symptom, but also improves the reserve capacity of the liver, as the levels of heno-Q cillastin and cholinesterase are also increased. It can be said that there is
Liver-8 = It is also useful in the treatment of various liver diseases such as inflammation.
以上that's all
Claims (1)
５′−サイクリックホスフェート又はその塩を有効成分
として含有する黄疸治療剤。1, N^■,2'-O-dibutyryladenosine-3',
A therapeutic agent for jaundice containing 5'-cyclic phosphate or a salt thereof as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP30250486A JPH0759514B2 (en) | 1986-12-18 | 1986-12-18 | Jaundice remedy |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP30250486A JPH0759514B2 (en) | 1986-12-18 | 1986-12-18 | Jaundice remedy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63154624A true JPS63154624A (en) | 1988-06-27 |
| JPH0759514B2 JPH0759514B2 (en) | 1995-06-28 |
Family
ID=17909757
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP30250486A Expired - Fee Related JPH0759514B2 (en) | 1986-12-18 | 1986-12-18 | Jaundice remedy |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0759514B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5405838A (en) * | 1990-09-28 | 1995-04-11 | Daiichi Pharmaceutical Co., Ltd. | Topical powder compositions containing a cyclic AMP derivative |
-
1986
- 1986-12-18 JP JP30250486A patent/JPH0759514B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5405838A (en) * | 1990-09-28 | 1995-04-11 | Daiichi Pharmaceutical Co., Ltd. | Topical powder compositions containing a cyclic AMP derivative |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0759514B2 (en) | 1995-06-28 |
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