インドメタシン 化學(xué)特性,用途語,生産方法
外観
白色～うすい黃色, 結(jié)晶性粉末～粉末
溶解性
中性, 弱酸性液中では安定であるが、濃いアルカリ液中では分解がおこる。水酸化ナトリウム溶液に可溶、メタノール, エーテル, クロロホルムに難溶、水に不溶。
解説
インドメタシン，いんどめたしん．ρ-メトキシフェニルヒドラジンとアセトアルデヒドとの反応物をρ-クロロベンゾイルクロリドでアシル化し，加水分解後，レブリン酸と加熱閉環(huán)すると得られる．白色～淡黃色の微細(xì)な結(jié)晶．融點(diǎn)155 ℃ と162 ℃ の2形がある．エタノール，エーテル，アセトンに可溶，水に不溶．光によって黃褐色に著色する．シクロオキシゲナーゼを阻害することによりプロスタグランジンの生合成を抑制する．pKa 4.5．効力が強(qiáng)く，低毒性の消炎，鎮(zhèn)痛薬．関節(jié)リウマチ，痛風(fēng)発作など炎癥性疾患に用いる．LD50 50 mg/kg(マウス，経口)．
用途
薬理研究用。
用途
インドール酢酸系化合物です。
シクロオキシゲナーゼ1（COX-1）を特異的
に阻害します。
用途
インドール酢酸系化合物です。シクロオキシゲナーゼⅠを特異的に阻害する作用を示します。
用途
インドメタシン（英: indometacin）とは非ステロイド性抗炎癥薬の一つ。アラキドン酸カスケードにおけるシクロオキシゲナーゼ（COX）を阻害することによりプロスタグランジン類の生成を抑制することによって抗炎癥作用を示す。また、抗炎癥作用以外に鎮(zhèn)痛作用を持つ。
用途
インドメタシン，非ステロイド性の解熱鎮(zhèn)痛剤。慢性関節(jié)リウマチならびに関連疾患の治療薬として 1963年に開発された。インドメタシンはインドール誘導(dǎo)體であるが，作用機(jī)序はサリチル酸誘導(dǎo)體と同様，プロスタグランジン生合成阻害によると考えられている。そのため，抗炎癥作用のほかに血栓，狹心癥，心筋梗塞，月経困難癥などにも応用されはじめている。副作用として食欲不振，吐き気，腹痛，消化性潰瘍などの消化器障害が最も多く，頭痛，めまい，白血球減少癥，血小板減少などもみられることがある。
効能
鎮(zhèn)痛薬, 抗炎癥薬, 解熱薬, シクロオキシゲナーゼ阻害薬
商品名
アコニップ (テイカ製薬); アコニップ (テイカ製薬); イドメシン (興和); イドメシン (興和); インサイド (久光製薬); インテナース (東光薬品工業(yè)); インテナース (東光薬品工業(yè)); インテナース (東光薬品工業(yè)); インテバン (帝國製薬); インテバン (帝國製薬); インテバン (帝國製薬); インテバン (帝國製薬); インドメタシン (ニプロ); インドメタシン (長生堂製薬); カトレップ (帝國製薬); カトレップ (帝國製薬); コリフメシン (東和製薬－和歌山); ゼムパック (救急薬品工業(yè)); ハップスター (大石膏盛堂); ラクティオン (テイカ製薬); ラクティオン (テイカ製薬)
説明
Aqueous solutions of indomethacin are not stable because of the ease of hydrolysis of the p-chlorobenzoyl group.
The original synthesis of indomethacin by Shen et al. involved the formation of 2-methyl-5-methoxyindole acetic
acid and subsequent
acylation after protection of the carboxyl group as the t-butyl ester. It was introduced in the United States in 1965. It
is still one of the most potent NSAIDs in use. It also is a more potent antipyretic than either aspirin or
acetaminophen, and it possesses approximately 10 times the analgetic potency of aspirin.
化學(xué)的特性
Crystalline Solid
使用
Inhibits cyclooxygenase (IC50=0.1uM) selectively over liposygenases (IC50=100uM for 5-,12- and 15-LO). A clinically useful NAISD
製造方法
acylation of sodium 2-(4-
methoxyphenyl)hydrazine-1-sulfonate with
4-chlorobenzoyl chloride followed by
heating yields 1-(4- chlorobenzoyl)-1-(4-
methoxyphenyl)hydrazine. Condensation with
levulinic acid in a Fischer indole synthesis affords indomethacin.
適応癥
Indomethacin (Indocin) is used in the treatment of
acute gouty arthritis, rheumatoid arthritis, ankylosing
spondylitis, and osteoarthritis. It is not recommended
for use as a simple analgesic or antipyretic because of its
potential for toxicity.While indomethacin inhibits both
COX-1 and COX-2, it is moderately selective for COX-
1. It produces more CNS side effects than most of the
other NSAIDs. Severe headache occurs in 25 to 50% of
patients; vertigo, confusion, and psychological disturbances
occur with some regularity. GI symptoms also
are more frequent and severe than with most other NSAIDs. Hematopoietic side effects (e.g., leukopenia,
hemolytic anemia, aplastic anemia, purpura, thrombocytopenia,
and agranulocytosis) also may occur. Ocular
effects (blurred vision, corneal deposits) have been observed
in patients receiving indomethacin, and regular
ophthalmological examinations are necessary when the
drug is used for long periods. Hepatitis, jaundice, pancreatitis,
and hypersensitivity reactions also have been
noted.
定義
The antiinflammatory drug indomethacin.
世界保健機(jī)関（WHO）
Indometacin was introduced in 1963 and it is one of the first
NSAIDs. Convulsions are rarely reported in relation with the use of this group of
agents. Indometacin farnesil is a pro-drug of indometacin, and the occurrence of
gastro-intestinal adverse effects could be expected. See also under nonsteroidal
antiinflammatory agents.
生物學(xué)の機(jī)能
Indomethacin (Indocin) is an acetic acid derivative related
functionally to sulindac (Clinoril), a prodrug with
a long half-life, and etodolac (Lodine).They are metabolized
in the liver and excreted as metabolites in the bile and via the kidney. They are potent inhibitors of
COX and thus extremely effective antiinflammatory
agents.
一般的な説明
Crystals.
空気と水の反応
Practically insoluble in water. Decomposes in alkali.
反応プロフィール
A weak organic acid.
火災(zāi)危険
Non-combustible, substance itself does not burn but may decompose upon heating to produce corrosive and/or toxic fumes. Some are oxidizers and may ignite combustibles (wood, paper, oil, clothing, etc.). Contact with metals may evolve flammable hydrogen gas. Containers may explode when heated.
応用例（製薬）
Indomethacin is a nonsteroidal anti-inflammatory agent used in pain and moderate to severe
inflammation in rheumatic diseases and other musculoskeletal disorders. It is a COX (cyclooxygenase)
inhibitor and therefore interrupts the production of prostaglandins.
A series of new silicon compounds, based on the structure of indomethacin, have been synthesised and
are under investigation as novel anticancer agents. The carboxyl group of indomethacin was reacted with
a series of amino-functionalised silanes. The resulting products have been shown to be significantly more
lipophilic and more selective to COX-2. Furthermore, in vitro testing has shown an increased uptake of the
new compounds at the tumour site. The silane-functionalised indomethacin derivatives exhibited a 15-fold
increased antiproliferative effect when tested against pancreatic cancer .
生物活性
Cyclooxgenase (COX) inhibitor; displays selectivity for COX-1 (IC 50 values are 230 and 630 nM for human COX-1 and COX-2 respectively). Widely used anti-inflammatory agent.
臨床応用
Indomethacin is available for the short-term treatment of acute gouty arthritis, acute pain of ankylosing spondylitis,
and osteoarthritis. An injectable form to be reconstituted also is available as the sodium trihydrate salt for IV use in
premature infants with patent ductus arteriosus. Because of its ability to suppress uterine activity by inhibiting
prostaglandin biosynthesis, indomethacin also has an unlabeled use to prevent premature labor.
副作用
All of these drugs produce analgesic effects, antipyresis,
and antiinflammatory effects.Due to the high incidence
of gastric irritation, headache, nausea, and other side effects,
including hematological effects and coronary
vasoconstriction, they are not useful as an initial treatment
for pain. GI irritation and ulceration occur to a
lesser extent with etodolac. Indomethacin is useful in
the treatment of acute gout, osteoarthritis, ankylosing
spondylitis, and acceleration of the closure of the ductus
arteriosus in premature infants. The tocolytic effects of
indomethacin to prevent preterm labor are the result of
its effects on prostaglandin synthesis. However, the toxicity
of the drug limits such application, since it increases
fetal morbidity. Indomethacin is contraindicated
in pregnancy, in asthmatics, and in those with gastric ulcers
or other ulceration of the GI tract. Indomethacin
may increase the symptoms associated with depression
or other psychiatric disturbances and those associated
with epilepsy and Parkinson’s disease. The drug should
be used with caution in such patients.
インドメタシン 上流と下流の製品情報(bào)
原材料
準(zhǔn)備製品