グリセロールトリニトラート 化学特性,用途語,生産方法
解説
ニトログリセリン,グリセリンの硝酸エステル。NGと略記される。1846年イタリアのソブレロによって初めて合成された。ソブレロ自身は、ニトログリセリンの爆発性があまりに激しいので使い物にならないと考えた。しかし、この強力な爆発威力に注目した人々によって鉱山で発破(はっぱ)用に使われていたが、たいへん敏感な液体で、岩の割れ目に流れ込んだりして予期しない爆発事故をおこした。また、凝固点が低いので冬には凍結し、それを溶かすときにも爆発事故をおこした。
ニトログリセリンは、それまで使われてきた黒色火薬の7倍の爆破威力があったが、黒色火薬と違って、導火線で点火したのでは燃えるだけで確実に爆発させることはできなかった。スウェーデンのノーベルは、ニトログリセリンを確実に爆発させるために雷管を発明（1864）して、ニトログリセリンおよびそれに続くダイナマイトの爆破薬としての用途を確立した。
ニトログリセリンはそのもの単独では危険すぎたので、ノーベルはそれを安全にして使える珪藻土(けいそうど)ダイナマイトおよびゼラチンダイナマイトを発明して、ニトログリセリンの爆薬原料としての用途を確立した。また、ニトログリセリンを窒素量12％前後のニトロセルロースと混ぜて高性能のダブルベース無煙火薬（バリスタイト）を発明した。このように、ニトログリセリンを実用化するためにノーベルの果たした役割は大きい。
用途
ダイナマイトの基材、狭心症の薬。液体のままニトログリセリンが工場外にでることはなく、工場内でダイナマイトに変えられる。また無煙火薬の主剤とする
効能
血圧降下薬, 冠血管拡張薬
商品名
ニトロダーム (サンファーマ); バソレーター (三和化学研究所); ミオコール (トーアエイヨー); ミニトロ (キョーリンリメディオ); ミニトロ (キョーリンリメディオ); ミリス (日本化薬); ミリスロール (日本化薬); ミリスロール (日本化薬); メディトランス (トーヨーケム)
性質
ニトログリセリンは無色透明の液体で甘味をもつ。水に難溶であるが有機溶媒に溶ける。窒素量12％前後のニトロセルロースを混合して膠化(こうか)し、ニトログリセリンの打撃や摩擦に対する感度を低下させて用いる。水酸化ナトリウム（カ性ソーダ）のアルコール溶液で分解し非爆発性となる。開放状態では少量のニトログリセリンは点火しただけでは爆発しないで燃えるだけである。密閉したり、大量であると爆発に移行する。ニトログリセリンの1滴を200℃付近の鉄板上に落とすと爆発するが、400℃付近では燃えるだけである。爆速は毎秒7500～8000メートルの高速爆速と、1500～2000メートルの低速爆速がある。
現在ダイナマイト原料のニトログリセリンとしては、ニトログリコールとの混合物が用いられている。ニトログリコールはニトログリセリンの不凍剤として用いられるようになったが、膠化促進剤としての役割も認められている。しかし、蒸気圧が高くて毒性も強く、過去にダイナマイト製造工場ではニトログリコール中毒事故をおこしたことがあった。そのため、日本では、ニトログリセリンとニトログリコールの混合液中のニトログリコール混合割合は最大38％に抑えられている。なお、ニトログリコールを取り扱う工程では、十分に換気を行い、また、皮膚接触を避ける方策が講じられている。
説明
Nitroglycerin is an oily, poisonous, clear to pale yellow, explosive liquid.Nitroglycerin is made by nitrating glycerol. Early industrial processes used a batch process
in which glycerol was added to a mixture with approximately equal volumes of nitric acid
and sulfuric acid.The sulfuric acid serves to ionize the nitric acid and removes water formed
in the nitration process.
化学的特性
Nitroglycerin is a pale yellow liquid or crystalline
solid (below 13℃).
来歴
It was first prepared
in 1846 by the Italian chemist Ascanio Sobrero (1812–1888), who nitrated glycerol using a
mixture of nitric acid and sulfuric acid. Sobrero, who was injured in an explosion doing his
research, realized the compound’s danger and abandoned work on nitroglycerin. Twenty years
after Sobrero’s discovery, Alfred Nobel (1833–1896) developed its use commercially. Nobel
mixed nitroglycerin with other substances, searching for a safe way to transport it and make it less sensitive to heat and pressure.
nitroglycerin when it was first marketed,and Nobel continued to experiment with methods to
make nitroglycerin safer.One of these was mixing nitroglycerin with materials to make a solid
form of nitroglycerin. Nobel discovered that when nitroglycerin was mixed with a silica-based
diatomaceous earth material called kieselguhr,a relatively stable product resulted.The mixture
produced a paste that Nobel could pack into cardboard tubes;these could then be inserted
into holes drilled into rock structures and detonated.In 1867,Nobel patented his mixture and
called it dynamite,a name derived from the Greek word dunamis, meaning power.Nobel also
perfected a blasting cap made from mercury fulminate (Hg(ONC)2) and potassium chlorate
(KClO3) to detonate the nitroglycerin.
使用
Nitroglycerin has medicinal use as a vasodilator. The main medical use of nitroglycerin is to treat angina pectoris. Nitroglycerin was first used to treat this condition in the late 19th century. It is prescribed today in various forms (tablet, ointment, patches, and injection) for patients who suffer from angina pectoris. Nitroglycerin is marketed under various trade names: Nitro-Dur, Nitrostat, Nitrospan, Nitro-Bid, and Tridil. When used in medications, the name glyceryl trinitrate is often used instead of nitroglycerin.
定義
ChEBI: A nitroglycerol that is glycerol in which the hydrogen atoms of all three hydroxy groups are replaced by nitro groups. It acts as a prodrug, releasing nitric oxide to open blood vessels and so alleviate heart pain.
調製方法
Nitroglycerin is made by nitrating glycerol.Early industrial processes used a batch processin which glycerol was added to a mixture with approximately equal volumes of nitric acidand sulfuric acid.The sulfuric acid serves to ionize the nitric acid and removes water formedin the nitration process.Removing the water formed in nitration increases the yield of nitroglycerin.Acids and water must be removed from the desired nitroglycerin through a washingprocess. The production of nitroglycerin is highly exothermic,and it is important to keepthe temperature below room temperature to prevent an explosion. Early production methodsused cooling coils in the nitration vessels to regulate the temperature.During the latter halfof the 20th century, safer continuous production methods replaced batch processes.In thesemethods much smaller reactors are required,as glycerol is reacted with the acids.
適応症
Nitroglycerin (also isosorbide nitrate) relaxes isolated
strips of human corpus cavernosum. Its mechanism
involves the stimulation of guanylate cyclase.
Clinically, nitroglycerin has been of limited use in the
treatment of ED.
医薬用
狭心症の発作の予防に古くから用いられている。希釈された場合には爆発力はない。舌下錠として口腔(こうくう)粘膜から吸収させて適用する。刺すような味を呈する。本剤は揮発性で、綿花、塩化ビニルなどのプラスチックに吸着されると効果が低下するので、保管にはガラス容器を用い、密栓する。最近では軟膏(なんこう)、プラスター（貼付(ちょうふ)薬）ができ、塗布または貼付して狭心症の予防に用いられる。さらに注射液として血圧降下の目的で点滴静脈注射で用いられる。
一般的な説明
Colorless to pale-yellow, viscous liquid or solid (below 56°F). (Note: An explosive ingredient in dynamite (20-40%) with ethylene glycol dinitrate (80-60%).).
空気と水の反応
Highly flammable.
反応プロフィール
Nitroalkanes, such as NITROGLYCERIN, range from slight to strong oxidizing agents. If mixed with reducing agents, including hydrides, sulfides and nitrides, they may begin a vigorous reaction that culminates in a detonation. Nitroalkanes are milder oxidizing agents, but still react violently with reducing agents at higher temperature and pressures. Nitroalkanes react with inorganic bases to form explosive salts. The presence of metal oxides increases the thermal sensitivity of nitroalkanes. Nitroalkanes with more than one nitro group are generally explosive. Nitroalkanes are insoluble in water. Flammable/combustible material. May be ignited by heat, sparks or flames. Nitroglycerin is incompatible with the following: Heat, ozone, shock, acids. Note: An OSHA Class A Explosive (1910.109). .
危険性
Severe explosion risk, highly sensitive to
shock and heat. Toxic by ingestion, inhalation, and
skin absorption. Toxic by skin absorption. Vasodilator.
健康ハザード
Severe acute poisoning may result from ingestion of nitroglycerine or inhalation of its dust. The acute toxic symptoms include headache, nausea, vomiting, abdominal pain, tremor, dyspnea, paralysis, and convulsions. In addition, methemoglobinemia and cyanosis may occur. Ingestion of a relatively smallamount, 1.5-2.0 g, could be fatal to humans. Inhalation of its vapors or dust at 0.3 mg/m
3 concentration in air produced an immediate fall in blood pressure and headache in human volunteers (ACGIH 1986). Chronic poisoning may produce headache and hallucination.
LD50 value, oral (rats): 105 mg/kg.
火災危険
HIGHLY FLAMMABLE: Will be easily ignited by heat, sparks or flames. Vapors may form explosive mixtures with air. Vapors may travel to source of ignition and flash back. Most vapors are heavier than air. They will spread along ground and collect in low or confined areas (sewers, basements, tanks). Vapor explosion hazard indoors, outdoors or in sewers. Runoff to sewer may create fire or explosion hazard. Containers may explode when heated. Many liquids are lighter than water.
接触アレルゲン
Nitroglycerin is an explosive agent contained in dynamite
and an antianginal and vasodilator treatment
available in systemic and topical forms. It is a well known irritant agent in dynamite manufacture. It can
also cause allergic reactions in employees of explosives
manufacturers and in the pharmaceutical industry.
Transdermal systems are the main source of
iatrogenic sensitization. Nitroglycerin can cross-react
with isosorbide dinitrate.
作用機序
Nitroglycerine reduces the load on the heart by dilating peripheral veins, reducing the
myocardial need for oxygen, and facilitating redistribution of coronary blood flow in the
region of the myocardium with reduced blood flow.
臨床応用
Nitroglycerin is used extensively as an explosive in dynamite.A solution of the ester, if spilled or allowed to evaporate,will leave a residue of nitroglycerin. To prevent anexplosion of the residue, the ester must be decomposed byadding alkali. Even so, the material dispensed is so dilutethat the risk of explosions does not exist. It has a strong vasodilatingaction and, because it is absorbed through theskin, is prone to cause headaches among workers associatedwith its manufacture. This transdermal penetration is whynitroglycerin is useful in a patch formulation. In medicine, ithas the action typical of nitrites, but its action develops moreslowly and is of longer duration. Of all the known coronaryvasodilatory drugs, nitroglycerin is the only one capable ofstimulating the production of coronary collateral circulationand the only one able to prevent experimental myocardialinfarction by coronary occlusion.
副作用
Vascular headache, postural hypotension, and reflex
tachycardia are common side effects of organic nitrate
therapy. Fortunately, tolerance to nitrate-induced headache
develops after a few days of therapy. Postural hypotension
and tachycardia can be minimized by proper
dosage adjustment and by instructing the patient to sit down when taking rapidly acting preparations. An effective
dose of nitrate usually produces a fall in upright
systolic blood pressure of 10 mm Hg and a reflex rise in
heart rate of 10 beats per minute. Larger changes than
these should be avoided, because a reduction in myocardial
perfusion and an increase in cardiac oxygen requirements
may actually exacerbate the angina.
Since nitrite ions oxidize the iron atoms of hemoglobin
and convert it to methemoglobin, there may be a
loss in oxygen delivery to tissues. While methemoglobinemia
does not follow therapeutic doses of organic nitrates,
it can be observed after overdosage or accidental
poisoning.
安全性プロファイル
Human poison by an
unspecified route. Poison experimentally by
ingestion, intraperitoneal, subcutaneous, and
intravenous routes. An experimental
teratogen. Other experimental reproductive
effects. A skin irritant. Questionable
carcinogen with experimental tumorigenic
data. Mutation data reported. It can cause
respiratory difficulties and death due to
respiratory paralysis by ingestion. The acute
symptoms of nitroglycerin poisoning are
headaches, nausea, vomiting, abdominal
cramps, convulsions, methemoglobinemia,
circulatory collapse and reduced blood
pressure, excitement, vertigo, fainting,
respiratory rales, and cyanosis. Toxic effects
may occur by ingestion, inhalation of dust,
or absorption through intact skin. Human
systemic effects by intravenous route:
encephalitis, miosis, corneal damage. Used
as a vasodilator and as an explosive.
A very dangerous fire hazard when
exposed to heat, flame, or by spontaneous
chemical reaction. A severe explosion
hazard when shocked or exposed to 03 ,
heat, or flame. Nitroglycerin is a powerful
explosive, very sensitive to mechanical
shock, heat, or UV radiation. Small
quantities of it can readily be detonated by a
hammer blow on a hard surface, particularly
when it has been absorbed in filter paper. It
explodes when heated to 215°C. Frozen
nitroglycerin is somewhat less sensitive than
the liquid. However, a half-thawed or
partially thawed mixture is more sensitive
than either one. When heated to
decomposition it emits toxic fumes of NOx.
職業ばく露
An explosive ingredient in dynamite
(20-40%) with ethylene glycol dinitrate (80-60%). It is also used in making other explosives, rocket propellants;
and medicine (vasodilator).
代謝
Nitroglycerin is a lipid-soluble substance that is rapidly
absorbed across the sublingual or buccal mucosa. Its onset
of action occurs within 2 to 5 minutes, with maximal
effects observed at 3 to 10 minutes. Little residual activity
remains 20 to 30 minutes after sublingual administration.
The plasma half-life of nitroglycerin, given sublingually or by spray, is estimated to be 1 to 3 minutes.
Nitroglycerin and other organic nitrate esters undergo
first-pass metabolism and are rapidly metabolized
in the liver by the enzyme glutathione organic
nitrate reductase.
輸送方法
UN1204 Nitroglycerin solution in alcohol with
not .1% nitroglycerin, Hazard Class: 3; Labels:
3-Flammable liquid. UN3064 Nitroglycerin, solution in
alcohol with .1% but not .5% nitroglycerin, Hazard
Class: 3; Labels: 3-Flammable liquid. UN0143
Nitroglycerin, desensitized with not ,40% nonvolatile,
water-insoluble phlegmatizer, by mass. It falls in Hazard
Class 1.1D (subsidiary hazard: 6.1).
不和合性
Heat, ozone, shock, acids. An OSHA
Class A Explosive (1910.109). Heating may cause violent
combustion or explosion. May explosively decompose on
shock, friction, or concussion. Reacts with ozone causing
explosion hazard.
廃棄物の処理
Do not wash into sewer.
Consult with environmental regulatory agencies for guidance
on acceptable disposal practices. Generators of waste
containing this contaminant (≥100 kg/mo) must conform
with EPA regulations governing storage, transportation,
treatment, and waste disposal.
グリセロールトリニトラート 上流と下流の製品情報
原材料
準備製品