JPH11504023A - Novel use of (S) -adenosyl-L-methionine (SAMe) - Google Patents
Novel use of (S) -adenosyl-L-methionine (SAMe)Info
- Publication number
- JPH11504023A JPH11504023A JP8532131A JP53213196A JPH11504023A JP H11504023 A JPH11504023 A JP H11504023A JP 8532131 A JP8532131 A JP 8532131A JP 53213196 A JP53213196 A JP 53213196A JP H11504023 A JPH11504023 A JP H11504023A
- Authority
- JP
- Japan
- Prior art keywords
- same
- focal
- adenosyl
- methionine
- ischemia
- 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
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
(57)【要約】 病巣性の持続的虚血により誘発される障害の腸管外処置のために、ＳＡＭｅ及びその生理学的に認容性の塩を患者１日当たり２０００ｍｇより多い適用量で使用すること。 (57) [Summary] Use of SAMe and its physiologically tolerated salts at a dosage of more than 2000 mg per patient per day for parenteral treatment of lesions induced by focal persistent ischemia.
Description
【発明の詳細な説明】 （Ｓ）−アデノシル−Ｌ−メチオニン（ＳＡＭｅ）の 新規使用 （Ｓ）−アデノシル−Ｌ−メチオニン（ＳＡＭｅ）及びその塩は、既に公知で ある（ＥＰ−ＰＳ １６２３２３参照）。既に、ＳＡＭｅが原則的に抗虚血作用 を有することは記載されている(Eur.J.Pharmacol．144: 211,1987;Jpn．J．Phar macol,46:225,1988; Eur．J．Pharmacol．166:231,1989;Jpn．J．Pharmacol．52 :141,1990)。特許（ＪＰ−ＰＳ）第１６８６９４７号明細書によれば、ＳＡＭｅ は、中枢障害に関連している種々の適応症において使用できる。この文献中には 、１００ｍｇ〜１５５０ｍｇの１日適用量が記載されている。 Atti e Memorie della Societe Medica del Lazio，Anno I,Nr．3，1983,1-14 から、神経障害を有する患者に３又は５ｇ／ｄａｙのＳＡＭｅ−適用量で処置 することが公知である。 Japan,J.Pharmacol．49,119-124(1989)中には、ラッテにおける一時的虚血の 後の１００ｍｇ／ｋｇの適用量でのＣａ−含量及びグルコース代謝に対する及び 死亡率に対するＳＡＭｅの作用が記載されている。 しかしながら、ＳＡＭｅの抗虚血作用は、全体的( global)の、かつ一時的な脳性虚血の処置の場合にのみ明らかにされていた。全 体的な脳性虚血は、例えば心臓停止の間に現れるような脳性の血液供給の完全な 障害に基因している。全体的な虚血の際の１物質の治療効果は、脳の他の種類の 虚血性疾患に転用可能ではなく、殊に例えば頭蓋内の血管の閉塞に基因する病巣 性(fokale)虚血には転用できないことは公知である（Cerebrovasc.Brain Metab. Rev.2:1,1990）。 その障害の際に致死的結果にまで至りうる病巣性虚血の重要な病因は、次のも のである −急性塞栓性虚血、例えば心臓塞栓、脂肪−、空気塞栓、 −血栓性虚血、いわゆる脳性ミクロ又はマクロ血管病がこれに属する、 −血流力学的な、例えば病巣性の血管痙攣に基因する虚血、 −免疫学的な炎症性メカニズムにより誘発される虚血。止血学的及び免疫学的全 身性疾患により誘発される病巣性虚血もこれに属する、 −血管プロセスの特別な形及び他の通常でない原因と関連している病巣性虚血、 −直接的又は間接的に病巣性虚血をもたらす外傷性脳障害及び脊髄障害（例えば 空間を要する脳内、硬膜下の、硬膜外の出血、脳挫傷及び裂傷）。 本発明の課題は、ＳＡＭｅ及びその生理学的に認容 性の塩を、少なくとも２０００ｍｇ／ｄａｙ／患者の適用量で、病巣性の持続的 虚血により誘発される障害の腸管外処置のために使用することである。 ＳＭＡｅは、生理学的に認容性の酸との塩の形で使用するのが有利である。好 ましい酸は塩酸、硫酸、燐酸、ギ酸、酢酸、クエン酸、酒石酸、メタンスルホン 酸、ｐ−トルエンスルホン酸及びブタンジスルホン酸である。 ＳＭＡｅ又はその塩は、前記の症状に対して少なくとも２０００ｍｇ／ｄａｙ ／患者、殊に少なくとも３０００ｍｇ／ｄａｙ／患者の適用量、かつ有利には少 なくとも７０００ｍｇ／ｄａｙ／患者の適用量が推奨される。本発明による高い 適用量の記載は、医薬品の明らかな準備の際の重要な指示である。 ＳＡＭｅは、通常は腸管外（静脈、動脈内又は筋肉内）で適用され、この際、 静脈内適用が最も有利な適用形である。前記の量は、患者に１〜２４時間にわた り数日間注入することができる。 ＳＡＭｅ又はその塩は、慣用の製剤学的適用形で液状で使用することができ、 例えば、溶液として使用することができる。この適用形は、作用物質を通常は１ 〜５０％、有利に５〜２０％の量で含有している。 本発明の使用のためには、ＳＡＭｅ６〜１８重量％をリジンと一緒に水中に含 有している適用形が特に好適である。このような適用形は、例えば次の組成を有 していてよい：ＳＡＭｅ４００ｍｇ、Ｌ−リジン３２４.３ｍｇ、ＮａＯＨ１１. ５ｍｇ及び注射用水４７２.１ｍｇ。 意外にも、病巣性虚血の治療において２０００ｍｇより多い適用範囲でＳＡＭ ｅを使用する場合には、他の治療に比べて、死亡率低下作用を示すことが明らか なった。 病巣性虚血による障害の際のＳＡＭｅの死亡率を低まる作用を、次の脳の臨床 検査の例で示す： 障害のある患者で、二重盲検条件下に２つのプラセボ（偽薬）対照検査を行っ た。真薬(Verum)群の患者を１日当たりＳＡＭｅ２４００ｍｇ又は３２００ｍｇ で１４日間静脈注射処置した。この条件下に認め得る程度の副作用は現れなかっ た。第１表から明らかなように、ＳＡＭｅでの処置は、プラセボ群中におけるよ りもよりも著しく低い死亡率を双方の真薬群でもたらした。この研究の特別性は 、患者を一般に虚血発作の後に１２〜２４時間の間に処置開始しでき、即ち血流 障害の開始の後、数時でにも臨床的作用がまなお立証できることである。 Detailed description of the invention Novel use of (S) -adenosyl-L-methionine (SAMe) (S) -adenosyl-L-methionine (SAMe) and its salts are already known (see EP-PS 162323). . It has already been described that SAMe basically has an anti-ischemic effect (Eur. J. Pharmacol. 144: 211, 1987; Jpn. J. Pharmacol, 46: 225, 1988; Eur. J. Pharmacol). 166: 231, 1989; Jpn. J. Pharmacol. 52: 141, 1990). According to the patent (JP-PS) 1686947, SAMe can be used in various indications related to central disorders. This document describes a daily application dose of 100 mg to 1550 mg. Atti e Memorie della Societe Medica del Lazio, Anno I, Nr. From 3,1983,1-14 it is known to treat patients with neuropathy with a SAMe-dose of 3 or 5 g / day. Japan, J. Pharmacol. 49,119-124 (1989) describe the effect of SAMe on Ca-content and glucose metabolism at a dose of 100 mg / kg after transient ischemia in Latte and on mortality. However, the anti-ischemic effect of SAMe has only been demonstrated in the treatment of global and transient cerebral ischemia. Global cerebral ischemia is due to complete impairment of the cerebral blood supply, such as occurs during cardiac arrest. The therapeutic effect of one substance during global ischemia is not divertible to other types of ischemic diseases of the brain, especially to fokale ischemia due to, for example, obstruction of intracranial blood vessels. It is known that can not be diverted (Cerebrovasc. Brain Metab. Rev. 2: 1, 1990). The important etiologies of focal ischemia that can lead to fatal consequences upon its injury are: acute embolic ischemia, such as cardiac emboli, fat, air embolism, thrombotic ischemia, The so-called cerebral micro- or macrovascular diseases belong to this group:-ischemia due to hemodynamic, for example focal, vasospasm;-ischemia induced by immunological inflammatory mechanisms. Also included are focal ischemia induced by hemostatic and immunological systemic diseases,-focal ischemia associated with special forms of vascular processes and other unusual causes,-direct or Traumatic encephalopathy and spinal cord disorders that indirectly result in focal ischemia (eg, intracerebral, subdural, epidural hemorrhage, brain contusion and tears requiring space). The object of the present invention is to use SAMe and its physiologically tolerable salts at a dosage of at least 2000 mg / day / patient for the parenteral treatment of lesions induced by focal persistent ischemia. That is. SMAe is advantageously used in the form of a salt with a physiologically tolerable acid. Preferred acids are hydrochloric, sulfuric, phosphoric, formic, acetic, citric, tartaric, methanesulfonic, p-toluenesulfonic and butanedisulfonic acids. For SMAe or its salts, a dosage of at least 2000 mg / day / patient, especially at least 3000 mg / day / patient, and advantageously at least 7000 mg / day / patient is recommended for the above-mentioned conditions. The description of the high dosage according to the invention is an important indication in the clear preparation of the medicament. SAMe is usually applied parenterally (intravenously, intraarterially or intramuscularly), with intravenous application being the most advantageous application form. Such an amount can be infused into the patient for several days over a period of 1 to 24 hours. SAMe or a salt thereof can be used in a liquid form in a conventional pharmaceutical application form, for example, as a solution. This application form contains the active ingredient usually in an amount of 1 to 50%, preferably 5 to 20%. For the use according to the invention, application forms containing 6 to 18% by weight of SAMe in water together with lysine are particularly preferred. Such an application form may, for example, have the following composition: 400 mg SAMe, 324.3 mg L-lysine, 11.5 mg NaOH and 472.1 mg water for injection. Surprisingly, it has been shown that the use of SAMe in the treatment of focal ischemia in a range of more than 2000 mg has a mortality-reducing effect compared to other treatments. The effects of SAMe on reducing mortality during lesions due to focal ischemia are shown in the following brain laboratory examples: In a disabled patient, two placebo (placebo) controls under double blind conditions An inspection was performed. Patients in the true drug (Verum) group were treated intravenously with 2400 mg or 3200 mg of SAMe per day for 14 days. No appreciable side effects appeared under these conditions. As is evident from Table 1, treatment with SAMe resulted in significantly lower mortality in both true drug groups than in the placebo group. The particularity of this study is that patients can generally begin treatment between 12 and 24 hours after an ischemic attack, i.e., the clinical effects can still be demonstrated several hours after the onset of impaired blood flow. is there.
───────────────────────────────────────────────────── フロントページの続き (81)指定国 ＥＰ(ＡＴ，ＢＥ，ＣＨ，ＤＥ， ＤＫ，ＥＳ，ＦＩ，ＦＲ，ＧＢ，ＧＲ，ＩＥ，ＩＴ，Ｌ Ｕ，ＭＣ，ＮＬ，ＰＴ，ＳＥ)，ＵＡ(ＡＭ，ＡＺ，ＢＹ ，ＫＧ，ＫＺ，ＭＤ，ＲＵ，ＴＪ，ＴＭ)，ＡＵ，ＢＧ ，ＢＲ，ＣＡ，ＣＮ，ＣＺ，ＨＵ，ＪＰ，ＫＲ，ＭＸ， ＮＯ，ＮＺ，ＰＬ，ＲＯ，ＳＧ，ＳＩ，ＳＫ，ＴＲ，Ｕ Ａ，ＵＳ (72)発明者 ラースロー ソボー ドイツ連邦共和国 Ｄ−69221 ドッセン ハイム ブーヘンヴェーク 38 (72)発明者 ゲルハルト グロス ドイツ連邦共和国 Ｄ−67346 シュパイ ヤー ヴィムプヘリングシュトラーセ ５────────────────────────────────────────────────── ─── Continuation of front page (81) Designated countries EP (AT, BE, CH, DE, DK, ES, FI, FR, GB, GR, IE, IT, L U, MC, NL, PT, SE), UA (AM, AZ, BY) , KG, KZ, MD, RU, TJ, TM), AU, BG , BR, CA, CN, CZ, HU, JP, KR, MX, NO, NZ, PL, RO, SG, SI, SK, TR, U A, US (72) Inventor Larslow Sobo Germany D-69221 Dossen Heim Buchenweg 38 (72) Inventor Gerhard Gross Germany D-67346 Spey Jah Wimpuheringstrasse 5
Claims (1)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19515275.1 | 1995-04-26 | ||
| DE19515275A DE19515275A1 (en) | 1995-04-26 | 1995-04-26 | New use of (S) -denosyl-L-methionine (SAMe) |
| PCT/EP1996/001570 WO1996033727A1 (en) | 1995-04-26 | 1996-04-13 | NOVEL USE OF (S)-ADENOSYL-L-METHIONINE (SAMe) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH11504023A true JPH11504023A (en) | 1999-04-06 |
Family
ID=7760373
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8532131A Pending JPH11504023A (en) | 1995-04-26 | 1996-04-13 | Novel use of (S) -adenosyl-L-methionine (SAMe) |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP0822820A1 (en) |
| JP (1) | JPH11504023A (en) |
| KR (1) | KR19990008061A (en) |
| CN (1) | CN1182367A (en) |
| AR (1) | AR001687A1 (en) |
| AU (1) | AU5646396A (en) |
| CA (1) | CA2216854A1 (en) |
| CZ (1) | CZ330597A3 (en) |
| DE (1) | DE19515275A1 (en) |
| HR (1) | HRP960196A2 (en) |
| IL (1) | IL117844A0 (en) |
| MX (1) | MX9707735A (en) |
| NO (1) | NO974941D0 (en) |
| WO (1) | WO1996033727A1 (en) |
| ZA (1) | ZA963296B (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE37913B1 (en) * | 1972-08-02 | 1977-11-09 | Bioresearch Sas | Salt of s-adenosyl-l-methionine |
| JPS59139319A (en) * | 1983-01-31 | 1984-08-10 | Fuji Kagaku Kogyo Kk | Remedy for body dysfunction caused by cerebral disorder |
| JPH02290896A (en) * | 1989-04-28 | 1990-11-30 | Fuji Kagaku Kogyo Kk | Novel s-adenosylmethionine derivative |
| DE4425280C2 (en) * | 1994-07-16 | 1997-05-07 | Knoll Ag | Use of (S) -denosyl-L-methionine and its physiologically tolerable salts for the treatment of reperfusion damage that is triggered after temporary focal ischemia |
-
1995
- 1995-04-26 DE DE19515275A patent/DE19515275A1/en not_active Withdrawn
-
1996
- 1996-04-08 IL IL11784496A patent/IL117844A0/en unknown
- 1996-04-13 AU AU56463/96A patent/AU5646396A/en not_active Abandoned
- 1996-04-13 MX MX9707735A patent/MX9707735A/en unknown
- 1996-04-13 WO PCT/EP1996/001570 patent/WO1996033727A1/en not_active Application Discontinuation
- 1996-04-13 KR KR1019970707585A patent/KR19990008061A/en not_active Application Discontinuation
- 1996-04-13 JP JP8532131A patent/JPH11504023A/en active Pending
- 1996-04-13 CN CN96193498A patent/CN1182367A/en active Pending
- 1996-04-13 CZ CZ973305A patent/CZ330597A3/en unknown
- 1996-04-13 CA CA002216854A patent/CA2216854A1/en not_active Abandoned
- 1996-04-13 EP EP96913500A patent/EP0822820A1/en not_active Withdrawn
- 1996-04-23 AR AR33625596A patent/AR001687A1/en unknown
- 1996-04-24 HR HR19515275.1A patent/HRP960196A2/en not_active Application Discontinuation
- 1996-04-25 ZA ZA9603296A patent/ZA963296B/en unknown
-
1997
- 1997-10-24 NO NO974941A patent/NO974941D0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AR001687A1 (en) | 1997-11-26 |
| KR19990008061A (en) | 1999-01-25 |
| CA2216854A1 (en) | 1996-10-13 |
| MX9707735A (en) | 1997-12-31 |
| ZA963296B (en) | 1997-10-27 |
| IL117844A0 (en) | 1996-08-04 |
| NO974941L (en) | 1997-10-24 |
| NO974941D0 (en) | 1997-10-24 |
| EP0822820A1 (en) | 1998-02-11 |
| HRP960196A2 (en) | 1998-02-28 |
| CZ330597A3 (en) | 1998-02-18 |
| CN1182367A (en) | 1998-05-20 |
| WO1996033727A1 (en) | 1996-10-31 |
| AU5646396A (en) | 1996-11-18 |
| DE19515275A1 (en) | 1996-10-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7235267B1 (en) | Brain cell or nerve cell-protecting agents comprising medicinal ginseng | |
| Xu et al. | Wogonin prevents TLR4-NF-κB-medicated neuro-inflammation and improves retinal ganglion cells survival in retina after optic nerve crush | |
| JP2020514391A (en) | Ultra long chain polyunsaturated fatty acids, erovanoid hydroxylated derivatives, and methods of use | |
| US9402818B2 (en) | Use of amides of mono- and dicarboxylic acids in the treatment of renal diseases | |
| JPH11505244A (en) | Treatment of mania and bipolar disorder | |
| PT792160E (en) | NEUROTROPHIC FACTOR DERIVED FROM GLIAL CELLS USED AS A NEUROPROTECTOR AGENT | |
| US6090775A (en) | Treatment of neurological conditions by an interleukin-1 inhibiting compound | |
| CN113546082B (en) | Application of telaprevir in preparation of medicine for treating ischemia/reperfusion injury and cytoprotective medicine | |
| KR100696417B1 (en) | Cerebrovascular regeneration/reconstruction-promoting agents and secondary nervous tissue degeneration-inhibiting agents comprising ginsenoside Rb1 | |
| US8097640B2 (en) | Prophylactic or therapeutic agent for diabetic maculopathy | |
| JP2017524727A (en) | SOCS1-derived peptides for use in chronic complications of diabetes | |
| JPH11504023A (en) | Novel use of (S) -adenosyl-L-methionine (SAMe) | |
| JP2001139483A (en) | Protecting agent for brain cell or nerve cell, consisting of ginseng | |
| CN113975276B (en) | Application of cobicistinib in preparation of medicines for treating ischemia/reperfusion injury and cytoprotective medicines | |
| Mubarak et al. | Effect of caffeine on serum tumour necrosis factor alpha and lactate dehydrogenase in Wistar rats exposed to cerebral ischaemia-reperfusion injury | |
| KR102089376B1 (en) | Composition comprising diamine derivatives for preventing or treating stroke, damage of nerve cells, parkinson's disease or amyotrophic lateral sclerosis | |
| KR100757226B1 (en) | A pharmaceutical composition comprising adatanserin for the treatment of neurodegenerative conditions | |
| KR20240024083A (en) | How to Control Neuropathy | |
| US20050130978A1 (en) | Novel crystal of quinoxalinedione derivative anhydride | |
| CN114617865A (en) | Application of acetyl L-carnitine in preparing medicine for preventing or treating venous outflow obstruction diseases | |
| US20080207631A1 (en) | Methods for the treatment and prevention of neurodegenerative conditions | |
| DE3402058A1 (en) | MEDICINE AGAINST CEREBRAL APOPLEXIA | |
| JPS59134722A (en) | Preventive and remedy for hemorrhagic infarction | |
| AU4752099A (en) | Treatment of neurological conditions by an interleukin-1 inhibiting compound |