ジゴキシン 化学特性,用途語,生産方法
外観
白色～ほとんど白色粉末～結晶
性質
C41H64O14(780.94)．ジゴキシンは，ゴマノハグサ科ケジギタリスDigitalis lanata Ehrh.やD.orientalis Lam.より得られる二次配糖体．酸によりジゴキシゲニン1分子とジギトキソース3分子に加水分解される．無色の結晶．融点約265 ℃(分解)．[α]D＋11°．エタノール，ピリジンに可溶，エーテル，アセトン，クロロホルムに不溶．肺水腫，心臓性喘息などのうっ血性心不全に有効である．LD50 0.23 mg/kg(ネコ)．森北出版「化学辞典（第2版）
用途
ジゴキシン（Digoxin）とはジギタリス属植物であるケジギタリスの葉から抽出される強心配糖体である。作用はジギトキシンより強く、作用時間が長い。ジゴキシンのアグリコン（非糖部）に相当する化合物はジゴキシゲニン (Digoxigenin) である。糖部であるジギトキソース (Digitoxose) は呈色反応であるケラー–キリアニ反応に対して陽性を示す。
ジゴキシンは細胞膜に存在するNa+/K+-ATPaseを阻害することによって細胞内Na+濃度の上昇をもたらす。結果、Na+を細胞へ取り込み、代わりにCa2+排出する経路として存在するNa+-Ca2+-交換体が抑制され、心筋細胞内Ca2+濃度の増加を引き起こし、心筋の収縮力の増加（陽性変力作用）、心拍数の減少（陰性変時作用）および心筋における神経興奮伝導速度の低下（陰性変伝導作用）を引き起こす。主に狭心症および心房細動に対して用いられる。副作用として嘔吐、不整脈などがある。
医薬用
ジゴキシンは，ゴマノハグサ科のケジギタリスから得られる二次配糖体。強心剤の一つ。消化吸収は 60～85%，作用発現は 15～30分，強心作用はジギトキシンより速く，ストロファンチンより遅い。生物学的半減期は 36時間，作用持続は中間型を示す。排泄は腎臓の糸球体ろ過により，尿細管再吸収は少い。一般のジギタリス製剤と同様，飽和と維持で心不全の治療をする。成人の総飽和量は経口投与で2～3mg，静脈注射で 0.75～1.5mg，維持量は経口投与，静脈注射とも1日あたり 0.25～0.5mgを目安とする。ジゴキシンの体内蓄積性を下げ，消化管吸収をよくしたβ-メチルジゴキシンが開発されている。
効能
強心薬
商品名
ジゴキシン (アルフレッサファーマ); ジゴキシン (ニプロ); ジゴキシン (京都薬品工業); ジゴシン (太陽ファルマ); ジゴシン (太陽ファルマ); ジゴシン (太陽ファルマ)
説明
Digoxin, 3β,14β-dihydroxy-5β-card-20(22)-enolide-3-rigitoxide, is also
a glycoside isolated from various types of foxgloves. It differs from digitoxin in that it has
an additional hydroxyl group at C16 of the steroid skeleton. It is extracted form the leaves
of Digitalis lanta, Digitalis orientalis, or Scrophulariaceae.
化学的特性
White Crystalline Powder
物理的性質
Appearance: white crystals or crystalline powder, odorless. Solubility: easily dissolved in pyridine, slightly soluble in dilute alcohol, slightly soluble in chloroform,
insoluble in water and ethyl ether. Specific optical rotation: +9.5 to +12.0°. Melting
point: 248–250?°C.
使用
Digoxin exhibits strong systolic action and slows heart rate. It is removed from the organism
faster than digitoxin. It is used from chronic cardiac insufficiency in decompensated
valvular disease of the heart, myocardium overload in arterial hypertension, tachycardia,
ventricular fibrillation, and other analogous situations.
定義
ChEBI: A cardenolide glycoside that is digitoxin beta-hydroxylated at C-12. A cardiac glycoside extracted from the foxglove plant, Digitalis lanata, it is used to control ventricular rate in atrial fibrillation and in the management
of congestive heart failure with atrial fibrillation, but the margin between toxic and therapeutic doses is small.
適応症
Digoxin is used for congestive heart failure (CHF), paroxysmal supraventricular
tachycarelia, atrial fibrillation, and atrial flutter.
一般的な説明
Digitalis (Crystodigin) is isolated fromD. lanata and D. purpurea among other Digitalis spp., and isthe chief active glycoside in digitalis leaf, with 1 mg digitoxinequal to 1 g of digitalis leaf therapy. In patients who missdoses, digitalis is very useful for maintenance therapy becauseof the longer half-life it provides. The longer durationand increased half-life are a result of the lack of the C-12hydroxy that is present in digoxin. In digoxin, this hydroxyplays two roles: (a) it serves as a site for metabolism, whichreduces the compound’s half-life; and (b) it gives more hydrophiliccharacter, which results in greater water solubilityand ease in renal elimination.
健康ハザード
Material is a digitalis glycoside. Ingestion can cause death. Material is considered super toxic; probable human oral lethal dose is less than 5 mg/kg, a taste (less than 7 drops) for a 70 kg (150 lb.) person. Persons at risk include those taking drugs for thyroid and renal diseases. Quinidine and diuretics taken concurrently with DIGOXIN can be hazardous. It should be used with extreme care during pregnancy and in nursing mothers.
火災危険
Avoid light.
安全性プロファイル
A deadly poison by
most routes. Human systemic effects by
ingestion: anorexia, cardlac arrhythmias,
nausea and vomiting, visual field changes,
pulse rate decrease, fall in blood pressure.
An experimental teratogen. When heated to
decomposition it emits acrid and irritating
fumes. See also DIGITALIS.
環境運命予測
Molecular weight: Digitoxin, 764.96; Digoxin, 780.96.
Cardiac glycosides have a characteristic chemical structure
called an aglycone ring. This is coupled with one or more
sugars. The aglycone portion of the glycoside includes
a steroid nucleus and a lactone ring at the C17 position.
Hydroxyl groups, oriented to the beta position, are present at
the C3 and C14 positions. Increases in numbers of hydroxyl
groups cause an increase in polarity and decrease in lipid
solubility. Increases in numbers of sugars also increase
polarity and reduce lipid solubility. Sugars are attached to the
steroid nucleus through a hydroxyl group at the C3 position
and influences solubility, absorption, toxicity, and other
pharmacological parameters.
純化方法
Crystallise digoxin from aqueous EtOH, aqueous pyridine, EtOH/CHCl3, and dry it in a vacuum at 100o. The melting point depends on heating rate, but when placed in a bath at 260o and heated slowly it decomposes at 265o. In EtOH it has max at 220nm ( 12,800). [Smith J Chem Soc 508 1930, X-ray: Go et al. Cryst Struct Commun 8 149, 1031 1979, Beilstein 18/4 V 381.] HIGHLY TOXIC.
ジゴキシン 上流と下流の製品情報
原材料
準備製品