カフェイン 化学特性,用途語,生産方法
外観
白色の結晶性粉末
定義
本品は、次の化学式で表される複素環式化合物である。
溶解性
水 (2.1g/100ml), エタノールに微溶, エーテルに難溶。水、エタノール及びアセトンにやや溶けにくい。
解説
1,3,7-trimethylxanthine．C8H10N2O2(194.19)．テイン(theine)ともいう．カフェイン，茶の葉，コーヒー豆，カカオの種子などに含まれる．構造上プリンアルカロイドの一つ．無色の柱状晶(昇華により精製)．融点238 ℃，昇華点178 ℃．水，エタノール，クロロホルム，エーテル，アセトン，ベンゼンに可溶．石油エーテル，リグロインに難溶．普通は一水和物で，絹糸状の光沢のある結晶体．苦味がある．興奮剤，利尿剤，強心剤として用いられる．茶の葉を熱湯で浸出し，塩基性酢酸鉛を加えてタンパク質，タンニンなどを沈殿させ，過剰の鉛を硫酸で除去し，その濾液からクロロホルムで抽出し，蒸発結晶させると得られる．テオフィリン，テオブロミンはともに茶の葉などに含まれ，利尿剤として用いられる．LD50 200 mg/kg(ネズミ，経口)．森北出版「化学辞典（第2版）
薬品
日本薬局方には、カフェインと無水カフェインが収載されている。1820年にコーヒー豆より発見され、1899年ドイツの有機化学者E・フィッシャーにより全合成された。現在では、天然物から抽出したものよりも合成品がよく用いられている。習慣作用が多少認められ、過量に摂取すると、集中力がなくなり、不眠、不安感、耳鳴りなどを訴える。劇薬。承認投与量の上限は、1回0.3グラム、1日2～3回経口投与。常用量は1回0.2グラム、1日0.5グラム経口投与される。
用途
薬理、生理作用研究用。有機合成原料。
用途
食品添加物(コーヒー飲料,コーヒー含有飲料),医薬 、飲料の興奮剤、食品のフレーバー成分、大脳に作用し呼吸器や循環器を刺激する。
食品
食品中では茶、コーヒーに多く含まれていて、これらにほろ苦いよい味を与えている味の成分であるとともに、興奮作用に役だっている。茶葉では高級なものほど多く含まれていて、玉露3.5％、抹茶(まっちゃ)3.2％、煎茶(せんちゃ)2.3％である。そのほか紅茶2.9％、インスタントコーヒー4.0％である。カフェインは、茶やコーヒーの抽出液に浸出され、その量は浸出条件（茶葉の量、湯の量や温度、浸出時間など）で異なるが、茶では初回の一煎がもっとも多く、二煎、三煎になるほど浸出量は減少する。
『L・F・フィーザー他著、後藤俊夫訳『有機化学実験』（1989・丸善）』▽『生田哲著『脳と心をあやつる物質――微量物質のはたらきをさぐる』（1999・講談社）』▽『ジョン・エムズリー、ピーター・フェル著、渡辺正訳『からだと化学物質――カフェインのこわさを知ってますか？』（2001・丸善）』▽『栗原久著『カフェインの科学――コーヒー、茶、チョコレートの薬理作用』（2004・学会出版センター）』▽『ベネット・アラン・ワインバーグ、ボニー・K・ビーラー著、別宮貞徳監訳『カフェイン大全――コーヒー・茶・チョコレートの歴史からダイエット・ドーピング・依存症の現状まで』（2006・八坂書房）』
化粧品の成分用途
皮膚コンディショニング剤、香料
効能
中枢神経刺激薬, アデノシン受容体拮抗薬, ホスホジエステラーゼ阻害薬
商品名
レスピア (ノーベルファーマ); 無水カフェイン (小堺製薬)
確認試験
(１) 本品の水溶液(1→500)2mLにタンニン酸試液を滴加
するとき，白色の沈殿を生じ，この沈殿は更にタンニン酸試
液を滴加するとき溶ける．
(２) 本品0.01gに過酸化水素試液10滴及び塩酸1滴を加え
て水浴上で蒸発乾固するとき，残留物は黄赤色を呈する．ま
た，これをアンモニア試液2～3滴を入れた容器の上にかざ
すとき，赤紫色に変わり，その色は水酸化ナトリウム試液2
～3滴を加えるとき，消える．
(３) 本品0.01gを水に溶かし50mLとする．この液5mLに
薄めた酢酸(31)(3 → 100)3mL 及び薄めたピリジン(1 →
10)5mLを加えて混和した後，薄めた次亜塩素酸ナトリウム
試液(1→5)2mLを加え，1分間放置する．これにチオ硫酸ナ
トリウム試液2mL及び水酸化ナトリウム試液5mLを加える
とき，黄色を呈する．
定量法
本品を乾燥し，その約0.4gを精密に量り，無水酢酸／
酢酸(100)混液(6：1)70mLに溶かし，0.1mol/L過塩素酸で滴
定する(指示薬：クリスタルバイオレット試液3滴)．
ただし，滴定の終点は液の紫色が緑色を経て黄色に変わると
きとする．同様の方法で空試験を行い，補正する．
0.1mol/L過塩素酸1mL＝19.42mg C
8H
10N
4O
2
純度試験
(１) 塩化物 本品2.0gを熱湯80mLに溶かし，20℃
に急冷し，水を加えて100mLとし，試料溶液とする．試料
溶液40mLに希硝酸6mL及び水を加えて50mLとする．これ
を検液とし， 試験を行う． 比較液には0.01mol/L 塩酸
0.25mLを加える(0.011％以下)．
(２) 硫酸塩 (1)の試料溶液40mLに希塩酸1mL及
び水を加えて50mLとする．これを検液とし，試験を行う．
比較液には0.005mol/L硫酸0.40mLを加える(0.024％以下)．
(３) 重金属〈1.07〉 本品2.0gをとり，第2法により操作し，
試験を行う．比較液には鉛標準液2.0mLを加える(10ppm以
下)．
(４) 類縁物質 本品0.10gをクロロホルム10mLに溶かし，
試料溶液とする．この液1mLを正確に量り，クロロホルム
を加えて正確に100mLとする．この液1mLを正確に量り，
クロロホルムを加えて正確に10mLとし，標準溶液とする．
これらの液につき，薄層クロマトグラフィーにより
試験を行う．試料溶液及び標準溶液10μLずつを薄層クロマ
トグラフィー用シリカゲル(蛍光剤入り)を用いて調製した薄
層板にスポットする．次にクロロホルム／エタノール(95)混
液(9：1)を展開溶媒として約10cm展開した後，薄層板を風
乾する．これに紫外線(主波長254nm)を照射するとき，試料
溶液から得た主スポット以外のスポットは，標準溶液から得
たスポットより濃くない．
(５) 硫酸呈色物 本品0.5gをとり，試験を行う．
液の色は色の比較液Dより濃くない．
貯法
容器 気密容器．
乾燥減量
0.5％以下(1g，80℃，4時間)．
強熱残分
0.1％以下(0.5g)．
説明
Caffeine is an alkaloid purine belonging to the group of organic compounds called methylxanthines. Pure caffeine is a white, crystalline, bitter-tasting compound. Caffeine is found in a number of plants, principally coffee and tea plants, as well as cola and cacao nuts. In plants, caffeine functions as a natural pesticide to deter insects.
化学的特性
Caffeine is the alkaloid 1,3,7-trimethylxanthine. It is one of the xanthine derivatives present up to 1.5% in seeds of
coffee (Coffea arabica L.) and up to 5% in the leaves of tea (Camelia sinensis). It is a component of the beverages made from these
plants. Caffeine is also a component of chocolate (Theobroma cacao) and the cola nut (Cola acuminata Schott and Endel. and related
species), the extract of which is used in cola drinks. It is virtually odorless. Caffeine is added to cola-type beverages for its enhancement
of flavor. Subtle and subliminal flavors are widely appreciated by consumers and caffeine has a modifying effect on other components
of the beverage. The threshold for detecting the presence of caffeine in liquid foods varies depending on the nature of other
substances present, but lies close to the level characteristic of currently produced cola-type beverages. The threshold for detection of
caffeine in water has been shown to be 0.0095%; in liquid foods, 0.0184%. In one study, panelists could distinguish a solution containing
0.0058% caffeine from the control. The threshold for detecting taste difference between an aqueous solution of caffeine and
a water control was also shown to be 0.005% caffeine and to distinguish bitterness, 0.011% caffeine. In aqueous solutions containing
threshold and subthreshold concentrations of caffeine, sucrose, citric acid and salt, all compounds depressed the taste intensity of
each other.*
物理的性質
Appearance: odorless silky needle-like crystal or crystal powder with the color of
white or a little yellowish green. Solubility: weathering, easily dissolved in water or
chloroform and slightly soluble in water, ethanol, or acetone, very slightly dissolved
in ether. Melting point: 235–238?°C.
天然物の起源
Reported found in coffee and guarana.
来歴
Runge isolated caff eine from coffee in 1819. Caffeine derives its name from the Kaffa region of Ethiopia. Caffeine comes from the German kaffeine, which in turn is derived from the German word for coffee, kaffee. In 1827, a compound isolated from tea was named theine, but this was eventually shown to be caffeine.
使用
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug and a reversible acetylcholinesterase inhibitor. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants.
In humans, caffeine acts as a central nervous system stimulant, temporarily warding off drowsiness and restoring alertness. Caffeine is a cardiac and respiratory stimulant; diuretic. Caffeine is toxic at sufficiently high doses.
定義
ChEBI: A trimethylxanthine in which the three methyl groups are located at positions 1, 3, and 7. A purine alkaloid that occurs naturally in tea and coffee.
適応症
This product is included in the Pharmacopoeia of the People’s Republic of China
(2015), the British Pharmacopoeia (2017), the United States Pharmacopeia (40), the
Japanese Pharmacopoeia (17th ed.), the European Pharmacopoeia (9.0th ed.), the
Indian Pharmacopoeia (2010), and the International Pharmacopoeia (5th ed.).
Commonly used dosage forms of caffeine include tablet, powder, and injection.
Mainly used dosage forms in the market include caffeine citrate tablets, amidopyrine caffeine tablets, amidopyrine caffeine, children acetaminophen aspirin caffeine
tablets, ergotamine caffeine tablets, caffeine sodium benzoate injection, cafe bromine agent, etc.
一般的な説明
Odorless white powder or white glistening needles, usually melted together. Bitter taste. Solutions in water are neutral to litmus. Odorless.
空気と水の反応
Efflorescent in air. Water soluble.
反応プロフィール
Caffeine may be hygroscopic. Aqueous solutions (1.12 mg/mL) are stable for three weeks at 41° F if protected from light. In normal room lighting and at room temperature, solutions are stable for 3 days. Solutions of Caffeine in water, DMSO, 95% ethanol or acetone should be stable for 24 hours under normal lab conditions. REACTIVITY: Caffeine may react with strong oxidizing agents. Caffeine is also incompatible with iodine, silver salts and tannins. Caffeine is a very weak base. Caffeine is decomposed by strong solutions of caustic alkalis.
危険性
One grain or more is toxic, 200 μg/m L has
been found to inhibit activity of the enzyme DNA
polymerase. Use in soft drinks not to exceed 0.02%.
Questionable carcinogen.
健康ハザード
Caffeine is a stimulant of the central nervoussystem. It eliminates fatigue and drowsiness. However, high doses cause gastrointestinal motility, restlessness, sleeplessness,nervousness, and tremor. Acute poisoningeffects include nausea, vomiting, headache,excitability, tremor, and sometimes, convulsive coma. Other symptoms may be respiratory depression, muscle contraction, distortedperception, and hallucination. Ingestion of15–20 g may be fatal to humans.
LD50 value, oral (mice): 127 mg/kg
LD50 value, oral (rabbits): 224 mg/kg
Animal studies indicate that caffeine athigh doses produces adverse reproductiveeffects, causing developmental abnormalities. It tested negative in the histidine reversion–Ames and TRP reversion tests.
火災危険
Flash point data for Caffeine are not available; however, Caffeine is probably combustible.
生物活性
Central nervous system stimulant. Antagonist at A 1 and A 2A adenosine receptors and inhibitor of cyclic nucleotide phosphodiesterases. Mobilises calcium from intracellular stores and inhibits benzodiazepine binding to GABA receptors.
臨床応用
The commonly used clinical preparations include caffeine sodium benzoate and
ergotamine caffeine. The preparation of caffeine sodium benzoate (injection) is constituted of 0.12?g/ml of caffeine, 0.13?g/ml of sodium benzoate, and cafe bromine
mixture (oral liquid). Clinically, it can be used for migraine headaches, cerebral artery dilated headache, or headache caused by histamine. However,
it is invalid in the prevention of headaches. The adverse reactions include nausea,
vomiting, abdominal pain, and fatigue. Other common symptoms include numbness
and tingling of the hands, toes, and face and swelling of the foot and lower limb.
Overdose causes severe poisoning, mental disorder, ataxia, convulsions, gray chills
of the hand and foot, sensory disturbance, and even death due to coma and respiratory paralysis. Caffeine citrate preparation, including injection and oral solution,
is the only internationally approved drug for the treatment of premature infant
apnea.
安全性プロファイル
A human poison by
ingestion. An experimental poison by
ingestion, subcutaneous, intraperitoneal,
intramuscular, rectal, and intravenous
routes. Human systemic effects: ataxia,
blood pressure elevation, change in heart
rate, changes in tubules, convulsions or
effect on seizure threshold, dtarrhea,
distorted perceptions, hallucinations,
hypermotility, muscle contraction,
musculoskeletal tumors, nausea or vomiting,
toxic psychosis, tremors. A human teratogen
causing developmental abnormalities of the
craniofacial and musculoskeletal systems,
pregnancy termination (abortion), and
stillbirth. Human maternal effects include an
unspecified effect on labor or chddbirth.
Human mutation data reported. An
experimental teratogen. Other experimental
reproductive effects. Questionable
carcinogen with experimental carcinogenic
data. Large doses (above 1.0 g> cause
palpitation, excitement, insomnia, dtzziness,
headache, and vomiting. Continued
excessive use of caffeine in tea or coffee
may lead to digestive disturbances,
constipation, palpitations, shortness of
breath, and depressed mental states. It is
also implicated in cardiac disorders under
those condttions. When heated to
decomposition it emits toxic fumes of NOx
環境運命予測
Caffeine can have profound effects on the cardiovascular
system. At least four mechanisms have been proposed for the
pro-arrhythmic potential of caffeine in overdose. First,
caffeine increases circulating catecholamines. Second, caffeine
inhibits phosphodiesterase. Increased circulating catecholamines
after caffeine overdose increase b1-receptor stimulation.
Stimulation of b1-receptors increases intracellular cAMP
by G protein stimulation of adenylate cyclase. The activity of
cAMP is prolonged due to its decreased metabolism as
phosphodiesterase is inhibited by caffeine. Subsequently,
b1-receptor effects are exaggerated and tachydysrhythmias are
induced. Third, caffeine increases myocardial intracellular calcium. Caffeine both induces release of calcium from the
sarcoplasmic reticulumand blocks calcium’s reuptake into the
sarcoplasmic reticulum. This resulting increase in cytosolic
calcium may provoke dysrhythmias. Fourth, caffeine blocks
cardiac adenosine receptors, which have been shown to be
antiarrhythmic.
The hypotension that has been noted with overdoses of
caffeine is due primarily to two mechanisms. First, caffeineinduced
tachydysrhythmias lead to inadequate filling of the
heart and subsequent decrease in cardiac output. Second,
caffeine augments β2-effects and causes subsequent vasodilation
with resulting hypotension.
純化方法
Caffeine crystallises from water or absolute EtOH. [Beilstein 26 III/IV 2338.]
カフェイン 上流と下流の製品情報
原材料
準備製品