アセチルサリチル酸 化学特性,用途語,生産方法
外観
白色の結晶
溶解性
水に難溶。エタノール, アセトンに易溶。水に難溶、エタノール, アセトンに易溶、エーテル, 水酸化ナトリウム溶液に可溶。エタノール及びアセトンに溶けやすく、水に溶けにくい。
解説
アセチルサリチル酸の別名で，サリチル酸の酢酸エステル。1899年ドレーザーDreserによって導入された古い医薬であるが，今日でも緩和な作用ながら抗炎症?解熱?鎮痛などの作用にもとづいて広く使用されている。白色の結晶または粉末で，わずかに酸味がある。アスピリンの薬理作用のメカニズムは，1982年度にノーベル賞を受けたイギリスのベーンJ.R.Vaneが1971年に発表した学説によって明らかになった。それは発熱，末梢血管拡張，痛みの感受性増大などの作用をもつ局所ホルモンであるプロスタグランジンE(prostaglandin E)などの生合成に関与する基本的な酵素(シクロオキシゲナーゼ)の働きを抑えることによるものである。
用途
鎮痛剤、解熱剤、抗リウマチ剤、血小板集合抑制剤。
用途
プロスタグランジンに関する研究、血小板の寿命を測定する"アスピリン法"、潰瘍誘発剤。
用途
サリチル酸系化合物です。シ
クロオキシゲナーゼ1（COX-1）を選択的に
阻害します。
用途
シクロオキシゲナーゼ1
（COX-1）を選択的に阻害し、プロスタグラ
ンジン生合成阻害作用を示します。
用途
サリチル酸の誘導体であるアセチルサリチル酸のこと。もともとはバイエル社の商品名であるが，今では非ステロイド性抗炎症剤の名として一般的である。主として皮膚の血管を拡張して熱の拡散を早めるので，鎮痛，解熱，抗炎症剤としてよく知られている。
効能
鎮痛薬, 抗炎症薬, 解熱薬, 抗リウマチ薬, 抗血小板薬, シクロオキシゲナーゼ阻害薬
商品名
アスピリン (バイエル薬品); アスピリン (マイラン製薬); アスピリン (丸石製薬); アスピリン (健栄製薬); アスピリン (吉田製薬); アスピリン (小堺製薬); アスピリン (山善製薬); アスピリン (日医工)
概要
アセチルサリチル酸（アセチルサリチルさん、英: acetylsalicylic acid）は、代表的な消炎鎮痛剤のひとつで非ステロイド性抗炎症薬の代名詞とも言うべき医薬品。ドイツのバイエル社が名付けた商標名のアスピリン（独: Aspirin）がよく知られ、日本薬局方ではアスピリンが正式名称になっている。
説明
Acetylsalicylic acid is a white crystalline powder commonly known by its common name as aspirin or ASA. Aspirin is the most widely used medication in the world.
化学的特性
Acetylsalicylic acid is a white crystalline solid with a slightly bitter taste. It is odorless but hydrolyzes in moist air to give an acetic acid odor
物理的性質
Acetylsalicylic acid, an acetyl derivative of salicylic acid, is a white, crystalline, weakly acidic substance, with a melting point of 136 °C , and a boiling point of 140 °C .
Synthesis The synthesis of aspirin is classified as an esterification reaction. Salicylic acid is treated with acetic anhydride, an acid derivative, causing a chemical reaction that turns salicylic acid's hydroxyl group into an ester group (R-OH → R-OCOCH
3). This process yields aspirin and acetic acid, which is considered a byproduct of this reaction.
Polymorphism Polymorphism, or the ability of a substance to form more than one crystal structure, is important in the development of pharmaceutical ingredients. Many drugs are receiving regulatory approval for only a single crystal form or polymorph. For a long time, only one crystal structure for aspirin was known. That aspirin might have a second crystalline form was suspected since the 1960s. The elusive second polymorph was first discovered by Vishweshwar and coworkers in 2005 , and fine structural details were given by Bond et al. .
来歴
The use of Acetylsalicylic acid goes back thousands of years, and there are numerous accounts of the medicinal properties of plants from the Salix (willow) and Myrtaceae (Myrtle) families. Writings from ancient civilizations indicate the use of willow bark in Mesopotamia and myrtle leaves in Egypt as medicines existing several thousand years b.c.e. Hippocrates (460–377 b.c.e. ) and the ancient Greeks used powdered willow bark and leaves to reduce fever (antipyretic) and as a pain reliever (analgesic). Willow and oil of wintergreen was used as medications by native Americans.
The chemical responsible for the medicinal properties in willow and oil of wintergreen are forms of salicylates, a general name to describe compounds containing the general structure of salicylic acid. Willows (genus Salix) contain salicin and oil of wintergreen contains methyl salicylate. Although the use of willow bark and oil of wintergreen as an accepted antipyretic and analgesic has occurred for at least 2,000 years, by the 19th century medicines were starting to be synthesized in chemical laboratories.
使用
Acetylsalicylic acid is the prototypical analgesic used in the treatment of mild to moderate pain. Acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Acetylsalicylic acid also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Along with sodium salicylate (sc-3520), aspirin has been shown to block the long terminal repeat from the human immunodeficiency virus and the Ig κ enhancer from NFκB dependent transcription.
適応症
Acetylsalicylic acid is available as capsules, tablets, enteric-coated
tablets (Ecotrin), timed-release tablets (ZORprin),
buffered tablets (Ascriptin, Bufferin), and as rectal suppositories.
Sodium salicylate is available generically.
Other salicylates include choline salicylate (Arthropan),
choline magnesium trisalicylate (Trilisate), and magnesium
salicylate (Momentum).
定義
ChEBI: A member of the class of benzoic acids that is salicylic acid in which the hydrogen that is attached to the phenolic hydroxy group has been replaced by an acetoxy group. A non-steroidal anti-inflammatory drug with moA cyclooxygenase inhibitor activity.
世界保健機関（WHO）
Acetylsalicylic acid, a nonsteroidal anti-inflammatory, analgesic and
antipyretic agent, was introduced into medicine in 1899 and has since been widely
available in over-the-counter preparations. Recent studies carried out in the USA
have shown an association between acetylsalicylic acid consumption in children and
the development of Reye's syndrome (a rare condition characterized by a
combination of encephalopathy and liver disorder and usually preceded by an acute
viral illness, such as influenza, diarrhoea, or chickenpox). Many drug regulatory
authorities have acted to caution against the use of the drug in children and young
adults with febrile conditions. Even within this group the risk of exposure is remote
and has been estimated to be of the order of 1.5 per million. This warning also
concerns products containing other salicylates. The new indication of acetylsalicylic
acid - prophylaxis of myocardial infarction due to its antithrombotic effect - requires
loneterm use and may lead to serious adverse reactions, including cerebral
haemorrhage. Acetylsalicylic acid retains a valuable place in medicine and remains in
the WHO Model List of Essential Drugs.
生物学の機能
Acetylsalicylic acid is one of the most important NSAIDs because
it decreases pain at predominantly peripheral
sites with little cortical interaction and thus has few
CNS effects. The prototypical COX-2 inhibitors are
celecoxib (Celebrex) and its chemical cousin, rofecoxib
(Vioxx). In addition to a role in inflammatory processes,COX-2 seems to play a role in colon cancer and
Alzheimer’s disease, providing potential additional uses
for COX-2-selective drugs.
獲得抵抗性
Acetylsalicylic acid is rapidly absorbed in the stomach and quickly degraded by plasma cholinesterases
(half-life, 15–20 min). A once-daily dose of 160 mg of aspirin, which is much lower than dosages
needed for its anti-inflammatory/analgesic actions, is sufficient to completely inactivate platelet
COX-1 irreversibly. Higher doses of aspirin only contribute to its side effects, especially
internal bleeding and upper gastrointestinal irritations.
一般的な説明
Acetylsalicylic acid (Aspro, Empirin), was introducedinto medicine by Dreser in 1899.Acetylsalicylic acid occurs as white crystals or as a white crystallinepowder and must be kept under dry conditions. It is not advisableto keep Acetylsalicylic acid products in the kitchen or bathroomcabinets, because Acetylsalicylic acid is slowly decomposed into aceticand salicylic acids in the presence of heat and moisture.Several proprietaries (e.g., Bufferin) use compounds such as sodium bicarbonate, aluminum glycinate, sodium citrate,aluminum hydroxide, or magnesium trisilicate to counteractAcetylsalicylic acid’s acidic property. One of the better antacids is dihydroxyaluminumaminoacetate. Acetylsalicylic acid is unusually effectivewhen prescribed with calcium glutamate. The more stable,nonirritant calcium acetylsalicylate is formed, and theglutamate portion (glutamic acid) maintains a pH of 3.5 to5. Practically all salts of Acetylsalicylic acid, except those of aluminumand calcium, are unstable for pharmaceutical use. Thesesalts appear to have fewer undesirable side effects and induceanalgesia faster than Acetylsalicylic acid. A timed release preparationof Acetylsalicylic acid is available. It does not appear to offer anyadvantages over Acetylsalicylic acid, except for bedtime dosage.
空気と水の反応
Slowly hydrolyzes in moist air. Has been involved in dust cloud explosions. Water insoluble. Solution in water is acid to methyl red indicator.
反応プロフィール
The active ingredient in common aspirin. Incompatible with oxidizers and strong acids. Also incompatible with strong bases. May react with water or nucleophiles (e.g. amines and hydroxy groups). May also react with acetanilide, amidopyrine, phenazone, hexamine, iron salts, phenobarbitone sodium, quinine salts, potassium and sodium iodides, alkali hydroxides, carbonates, stearates and paracetanol.
危険性
An allergen; may cause local bleeding espe-
cially of the gums; 10-g dose may be fatal. May
cause excessive biosynthesis of prostaglandins.
Dust dispersed in air is serious explosion risk. Skin
and eye irritant.
火災危険
Acetylsalicylic acid is combustible.
薬理学
Acetylsalicylic acid is a weak acid, and very little of it is ionized in the stomach after oral administration. Acetylsalicylic acid is poorly soluble in the acidic conditions of the stomach, which can delay absorption of high doses for eight to 24 hours. The increased pH and larger surface area of the small intestine causes aspirin to be absorbed rapidly there, which in turn allows more of the salicylate to dissolve. Owing to the issue of solubility, however, aspirin is absorbed much more slowly during overdose, and plasma concentrations can continue to rise for up to 24 hours after ingestion.
副作用
ContraindicationsAcetylsalicylic acid should not be taken by people who are allergic to ibuprofen or naproxen , or who have salicylate intolerance[70][71] or a more generalized drug intolerance to NSAIDs, and caution should be exercised in those with asthma or NSAID - precipitated bronchospasm.
GastrointestinalAcetylsalicylic acid use has been shown to increase the risk of gastrointestinal bleeding . Although some enteric-coated formulations of Acetylsalicylic acid are advertised as being "gentle to the stomach", in one study, enteric coating did not seem to reduce this risk. Combining Acetylsalicylic acid with other NSAIDs has also been shown to further increase this risk.
Central effectsLarge doses of salicylate, a metabolite of Acetylsalicylic acid, have been proposed to cause tinnitus (ringing in the ears) based on experiments in rats, via the action on arachidonic acid and NMDA receptors cascade.
Reye syndrome Reye syndrome, a rare but severe illness characterized by acute encephalopathy and fatty liver, can occur when children or adolescents are given Acetylsalicylic acid for a fever or other illnesses or infections.
安全性プロファイル
Poison by ingestion, intraperitoneal, and possibly other routes. Human systemic effects by ingestion: acute pulmonary edema, body temperature increase, changes in kidney tubules, coma, constipation, dehydration, hematuria, hepatitis, nausea or vomiting, respiratory stimulation, somnolence, tinnitus, decreased urine volume. Implicated in aplastic anemia. A 10 gram dose to an adult may be fatal. A human teratogen. Human reproductive effects by ingestion and possibly other routes: menstrual cycle changes, parturition, various effects on newborn including Apgar score, developmental abnormalities of the cardlovascular and respiratory systems. Experimental animal reproductive effects. Human mutation data reported. An allergen; skin contact, inhalation, or ingestion can cause asthma, sneezing, irritation of eyes and nose, hves, and eczema. Combustible when exposed to heat or flame. When heated to decomposition it emits acrid smoke and fumes.
職業ばく露
Used as an over-the counter and proprietary pharmaceutical and veterinary drug. Those engagedin manufacture of aspirin or, more likely, in its consumption in widespread use as an analgesic, antipyretic, and antiinflammatory agent
環境運命予測
The toxicity of Acetylsalicylic acid is multifactorial. Gastrointestinal symptoms such as nausea, vomiting, and abdominal pain occur as a result of both local gastric irritation and stimulation of the medullary chemoreceptor trigger zone. Salicylates directly stimulate the respiratory drive in the brain stem, leading to hyperventilation and respiratory alkalosis. Anion gap metabolic acidosis occurs from a buildup of organic acids as well as the uncoupling of oxidative phosphorylation, which results in an imbalance in ATP consumption and production, resulting in a net buildup of hydrogen ions. Therefore, Acetylsalicylic acid often causes a mixed acid–base status. Furthermore, the uncoupling of oxidative phosphorylation results in failure to produce ATP despite increased oxygen utilization, which leads to heat production and hyperthermia. Acetylsalicylic acid interferes with glucose metabolism and gluconeogenesis, and can cause profound decreases in cerebrospinal fluid glucose concentrations despite normal blood glucose concentrations.
輸送方法
UN2811 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required
純化方法
Crystallise aspirin twice from toluene, wash it with cyclohexane and dry it at 60o under vacuum for several hours [Davis & Hetzer J Res Nat Bur Stand 60 569 1958]. It has been recrystallised from isopropanol and from diethyl ether/pet ether (b 40-60o). It crystallises from EtOH (m 143-144o), *C6H6 (m 143o), hexane (m 115o and 128o), octane (m 121o), and has m 110o after sublimation. It has pK2 6 3.69(H2O), 4.15(20% aqueous EtOH), 4.47(30% aqueous EtOH) and 4.94(40% aqueous EtOH). It is an analgesic. [Beilstein 10 H 67, 10 II 41, 10 III 102, 10 IV 138.]
不和合性
Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides, carbonates, moisture. Dust dispersed in air is explosive
廃棄物の処理
May be flushed to sewer with large volumes of water.
アセチルサリチル酸 上流と下流の製品情報
原材料
準備製品