JP3388778B2 - Cerebrovascular dementia improving agent - Google Patents
Cerebrovascular dementia improving agentInfo
- Publication number
- JP3388778B2 JP3388778B2 JP13760792A JP13760792A JP3388778B2 JP 3388778 B2 JP3388778 B2 JP 3388778B2 JP 13760792 A JP13760792 A JP 13760792A JP 13760792 A JP13760792 A JP 13760792A JP 3388778 B2 JP3388778 B2 JP 3388778B2
- Authority
- JP
- Japan
- Prior art keywords
- improving agent
- cerebrovascular dementia
- agent according
- improvement
- symptom
- 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 - Fee Related
Links
Landscapes
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明は、下記式（１）で示され
るＮ−（２，６−ジメチルフェニル）−２−（２−オキ
ソ−１−ピロリジニル）アセタミド（以下、化合物Ａと
記す）又はその塩を有効成分とする脳血管性痴呆精神症
状改善剤に関する。The present invention relates to N- (2,6-dimethylphenyl) -2- (2-oxo-1-pyrrolidinyl) acetamide represented by the following formula (1) (hereinafter referred to as compound A) Or cerebrovascular dementia psychosis containing the salt as an active ingredient
It relates to a condition improver.
【０００２】[0002]
【化１】 [Chemical 1]
【０００３】[0003]
【従来の技術】脳血管性痴呆は、日本では老令人口比の
急増と共に、その患者数が近年増加しており、本疾病に
対する適切な治療法が確立していないことから、本疾病
の治療及び介護が大きな社会問題としてとりあげられて
いる。このような状況下で、本疾病に対し有効な薬剤を
見い出すべく様々な薬剤が検討されてきたが、臨床上満
足すべき程度に有用と判断されるものは何ら見い出され
ていない。2. Description of the Related Art Cerebrovascular dementia has been treated in Japan because the number of patients has been increasing in recent years with the rapid increase in the proportion of the elderly population, and an appropriate treatment method for this disease has not been established. And nursing care is taken up as a big social problem. Under such circumstances, various drugs have been studied in order to find an effective drug for this disease, but none have been found to be clinically satisfactory.
【０００４】一方、化合物Ａは、動物実験において、血
中酸素減少に基づく生存時間延長効果や脳障害後の記銘
力改善効果を有することが知られている（特公昭６２−
５４０４号参照）。しかし、本化合物の脳血管性痴呆精
神症状に対する臨床上の改善効果は知られていない。On the other hand, compound A is known to have an effect of prolonging survival time based on decrease in blood oxygen and an effect of improving memory after brain injury in animal experiments (Japanese Patent Publication No. 62-62-62).
5404). However, cerebrovascular dementia rectification of the compound
The clinical improvement effect on divine symptoms is unknown.
【０００５】本発明者等は、化合物Ａを脳血管性痴呆の
患者に投与した結果、従来では全く考えられなかった痴
呆精神症状の優れた改善効果が得られることを見い出
し、本発明を完成した。The present inventors have found that, as a result of administering Compound A to a patient with cerebrovascular dementia, an excellent effect of improving dementia and psychiatric symptoms, which has never been considered in the past, was obtained, and the present invention was completed. .
【０００６】[0006]
【発明の構成】本発明は、化合物Ａ又はその塩を有効成
分とする脳血管性痴呆精神症状改善剤に関する。化合物
Ａは、経口又は非経口投与され、その投与量は経口投与
の場合、成人に対し６０ｍｇ／日〜９００ｍｇ／日の範
囲である。化合物Ａを含有する製剤型としては錠剤、カ
プセル剤、丸剤、乳剤、懸濁剤、細粒剤等をあげること
ができ、これらの製剤は、通常の賦形剤と共に、公知の
製剤技術を用いて製造することができる。The present invention relates to a cerebrovascular dementia psychiatric symptom improving agent containing compound A or a salt thereof as an active ingredient. Compound A is orally or parenterally administered, and the dose is, when orally administered, in the range of 60 mg / day to 900 mg / day for an adult. Examples of the formulation type containing the compound A include tablets, capsules, pills, emulsions, suspensions, fine granules, etc. Can be manufactured using.
【０００７】化合物Ａは、安全性の高い化合物であり、
その急性毒性（ＬＤ50）は、マウスの雄では２００５ｍ
ｇ／ｋｇ（経口投与）で、同種の雌では１９４０ｍｇ／
ｋｇ（経口投与）であり、又臨床上でも安全性の高いこ
とが確認された。Compound A is a highly safe compound,
Its acute toxicity (LD 50 ) is 2005 m in male mice.
g / kg (orally), 1940 mg / in females of the same species
It was confirmed that the dose was kg (oral administration) and that it was clinically highly safe.
【０００８】[0008]
【発明の効果】化合物Ａは、脳血管性痴呆の患者の中核
症状である見当識障害（時間、場所）等の知的機能低下
及び周辺症状の自発性低下、情緒障害、対人接触障害、
問題行動等の精神症候全般に対し優れた改善効果が認め
られた。従って、化合物Ａは、脳血管性痴呆精神症状の
改善剤として極めて優れたものである。以下、本発明を
更に実施例により説明するが、本発明はこれに限定され
るものではない。EFFECTS OF THE INVENTION Compound A is a core symptom of cerebrovascular dementia, which is a decrease in intellectual function such as disorientation (time, place) and a spontaneous decrease in peripheral symptoms, emotional disorder, interpersonal contact disorder,
An excellent improving effect was observed on all mental symptoms such as problematic behavior. Therefore, Compound A is extremely excellent as an agent for improving psychiatric symptoms of cerebrovascular dementia. Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.
【０００９】[0009]
【実施例】ＣＴ（Ｘ線断層撮影）で梗塞、もしくは出血
巣を認め、痴呆の簡易診断に繁用されている長谷川式簡
易知能診査スケールの得点で２２点未満の脳血管性痴呆
患者１４５例に化合物Ａを１日量として１５０〜４５０
ｍｇを８週間経口投与した。投与患者については、投与
前ならびに投与後４週及び８週に脳機能改善薬に繁用さ
れている症状評価尺度、長谷川式簡易知能診査スケール
（ＨＤＳ）により痴呆の臨床症状を評価した。さらに、
これらの所見を勘案して全般改善度（ＦＧＩＲ）、概括
安全度（ＯＳＲ）を評価した。[Examples] 145 patients with cerebrovascular dementia who have an infarction or hemorrhagic foci on CT (X-ray tomography) and have a score of less than 22 on the Hasegawa-type simplified intelligence examination scale that is frequently used for simple diagnosis of dementia Compound A as daily dose of 150-450
Oral administration of mg for 8 weeks. For the treated patients, the clinical symptoms of dementia were evaluated by the Hasegawa-type simplified intelligence examination scale (HDS), which is a symptom rating scale commonly used for cerebral function-improving drugs before and 4 and 8 weeks after the administration. further,
Considering these findings, the overall improvement level (FGIR) and general safety level (OSR) were evaluated.
【００１０】ＦＧＩＲ及びＯＳＲの結果を表１に、症状
別の改善度（％）を表２に示した。The results of FGIR and OSR are shown in Table 1, and the degree of improvement (%) for each symptom is shown in Table 2.
【００１１】[0011]
【表１】 [Table 1]
【００１２】〔ＦＧＩＲ〕Ｉ：著明改善、II：中等度改
善、III ：軽度改善、IV：不変、Ｖ：悪化、ＤＰ：脱落
〔ＯＳＲ〕 Ｉ：安全（副作用なし）、II：ほぼ安全、
III ：安全性に問題あり、IV：安全でない[FGIR] I: marked improvement, II: moderate improvement, III: mild improvement, IV: unchanged, V: worse, DP: dropout [OSR] I: safe (no side effects), II: almost safe,
III: There is a problem with safety, IV: Not safe
【００１３】[0013]
【表２】 [Table 2]
【００１４】上表から明かな如く、化合物Ａは脳血管性
痴呆患者の自発性低下、情緒障害、対人接触障害、知的
機能低下、問題行動といった精神症候について改善効果
を示し、これらの症状の推移を総合的に評価した全般改
善度は７２．７％と優れた成績であった。As is clear from the above table, Compound A has an improving effect on mental symptoms such as spontaneous hypoactivity, emotional disorder, interpersonal contact disorder, intellectual function decline and problem behavior in patients with cerebrovascular dementia. The overall improvement, which was evaluated comprehensively, was 72.7%, which was an excellent result.
【００１５】一般に脳血管性痴呆では、その前段階にあ
る脳血管障害後遺症に比べ薬物治療効果は劣るとされて
いる。化合物Ａの脳血管性痴呆の全般改善は７２．７％
と脳血管障害後遺症に対する従来の脳機能改善薬の改善
度（約７０％）と比べても同等以上である。更に痴呆の
中核症状である知的機能低下に対する薬物療法の有用性
は疑問視されているが、化合物Ａのこれに対する改善度
は４６％で、プラセボの２５％、他の脳機能改善剤の３
５％程度に比べても高い。一方、安全性については、４
例（３％）に一過性の副作用が認められたのみで、概括
安全度は９７．９％と安全性は極めて高いことが確認さ
れた。以上の結果から、化合物Ａの脳血管性痴呆に対す
る改善効果は従来本疾患に対して投与されてきた薬剤に
比べ極めて優れたものであった。In general, cerebrovascular dementia is considered to be inferior in drug treatment effect to the sequelae of cerebrovascular accident in the preceding stage. Overall improvement of cerebrovascular dementia with Compound A was 72.7%.
And the degree of improvement (about 70%) of the conventional cerebral function-improving drugs for the sequelae of cerebrovascular accidents is at least equivalent. Further, the usefulness of drug therapy for intellectual impairment, which is a core symptom of dementia, has been questioned. However, the degree of improvement of Compound A is 46%, that of placebo is 25%, and that of other brain function improving agents is 3%.
It is higher than 5%. On the other hand, regarding safety, 4
Only one case (3%) had a transient side effect, and it was confirmed that the overall safety was 97.9% and the safety was extremely high. From the above results, the improving effect of the compound A on cerebrovascular dementia was extremely superior to the drugs conventionally administered to the present disease.
───────────────────────────────────────────────────── フロントページの続き (56)参考文献 Ａｄｖ．Ｂｅｈａｖ．Ｂｉｏｌ．, （1990），38Ｂ（Ｂａｓｉｃ，Ｃｌｉ ｎ．，Ｔｈｅｒ．Ａｓｐｅｃｔｓ Ａｌ ｚｈｅｉｍｅｒ’ｓ Ｐａｒｋｉｎｓｏ ｎ’ｓ Ｄｉｓ．，Ｖｏｌ．２），ｐ 371−374 (58)調査した分野(Int.Cl.7，ＤＢ名) A61K 31/40 C07D 207/27 ＣＡ（ＳＴＮ) ＲＥＧＩＳＴＲＹ（ＳＴＮ)─────────────────────────────────────────────────── ─── Continuation of the front page (56) References Adv. Behav. Biol. , (1990), 38B (Basic, Clin., Ther. Aspects Al zheimer's Parkinson's Dis., Vol. 2), p 371-374 (58) Fields investigated (Int. Cl. 7 , DB). Name) A61K 31/40 C07D 207/27 CA (STN) REGISTRY (STN)
Claims (7)
−（２−オキソ−１−ピロリジニル）アセタミド又はそ
の塩を有効成分とする脳血管性痴呆精神症状改善剤。1. N- (2,6-dimethylphenyl) -2
A cerebral vascular dementia psychiatric symptom improving agent comprising-(2-oxo-1-pyrrolidinyl) acetamide or a salt thereof as an active ingredient.
る特許請求の範囲第１項記載の改善剤。2. The improving agent according to claim 1, wherein the object of improvement is psychiatric symptoms of cerebrovascular dementia.
る特許請求の範囲第１項記載の改善剤。3. The improving agent according to claim 1, wherein the object of improvement is a core symptom of cerebrovascular dementia.
の範囲第１項又は３項記載の改善剤。4. The improving agent according to claim 1 or 3, wherein the core symptom is a decline in intellectual function.
求の範囲第１項又は４項記載の改善剤。5. The improving agent according to claim 1 or 4, wherein the decline in intellectual function is a disorientation.
る特許請求の範囲第１項記載の改善剤。6. The improving agent according to claim 1, wherein the object of improvement is peripheral symptoms of cerebrovascular dementia.
接触障害及び問題行動のいずれかである特許請求の範囲
第１項又は６項記載の改善剤。7. The improving agent according to claim 1 or 6, wherein the peripheral symptom is any of spontaneous deterioration, emotional disorder, interpersonal contact disorder and problematic behavior.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP13760792A JP3388778B2 (en) | 1991-05-02 | 1992-05-01 | Cerebrovascular dementia improving agent |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3-229818 | 1991-05-02 | ||
| JP22981891 | 1991-05-02 | ||
| JP13760792A JP3388778B2 (en) | 1991-05-02 | 1992-05-01 | Cerebrovascular dementia improving agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH05163145A JPH05163145A (en) | 1993-06-29 |
| JP3388778B2 true JP3388778B2 (en) | 2003-03-24 |
Family
ID=26470857
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP13760792A Expired - Fee Related JP3388778B2 (en) | 1991-05-02 | 1992-05-01 | Cerebrovascular dementia improving agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3388778B2 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU727482B2 (en) | 1996-10-01 | 2000-12-14 | Daiichi Pharmaceutical Co., Ltd. | Mitochondrial membrane stabilizer |
| KR20010021897A (en) | 1997-07-15 | 2001-03-15 | 스즈키 다다시 | Prophylactic or Therapeutic Agent for Amnesia |
| JPH1180027A (en) * | 1997-09-12 | 1999-03-23 | Dai Ichi Seiyaku Co Ltd | Intellect activator |
| DE60138733D1 (en) | 2000-12-28 | 2009-06-25 | Hamilton Pharmaceuticals Inc | MEDICAMENT FOR TREATMENT AND PREVENTION OF NEUROGENIC PAIN |
| WO2003018005A1 (en) * | 2001-08-22 | 2003-03-06 | Daiichi Pharmaceutical Co., Ltd. | use of nefiracetam for treating neurodegeneration |
-
1992
- 1992-05-01 JP JP13760792A patent/JP3388778B2/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| Ａｄｖ．Ｂｅｈａｖ．Ｂｉｏｌ．，（１９９０），３８Ｂ（Ｂａｓｉｃ，Ｃｌｉｎ．，Ｔｈｅｒ．Ａｓｐｅｃｔｓ Ａｌｚｈｅｉｍｅｒ’ｓ Ｐａｒｋｉｎｓｏｎ’ｓ Ｄｉｓ．，Ｖｏｌ．２），ｐ３７１−３７４ |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH05163145A (en) | 1993-06-29 |
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