ビンクリスチン硫酸塩 化学特性,用途語,生産方法
外観
白色～わずかにうすい褐色, 結晶性粉末～粉末
溶解性
水に可溶
用途
キインドールアルカロイドで
す。より強い毒性を示します。β- チューブ
リンに結合することにより、チューブリンの
重合を阻害し、微小管形成阻害作用を示しま
す。
用途
インドールアルカロイドで
す。β- チューブリンに結合することにより、
チューブリンの重合を阻害し、微小管形成阻
害作用を示します。
効能
抗悪性腫瘍薬, 微小管重合阻害薬
商品名
オンコビン (日本化薬)
使用上の注意
不活性ガス封入
化学的特性
Crystalline Solid
使用
Vincristine sulfate, is used as an anticancer agent, microtubule disrupter, Induces apoptosis in human lymphoma cells. Other applications include as a cell cycle arresting, apoptotic inducing alkaloid.
一般的な説明
Vincristine sulfate appears as an anticancer drug. White to slightly yellow, amorphous or crystalline powder. Sensitive to light. Odorless. pH (0.1% solution) 3.5 - 4.5. (NTP, 1992)
空気と水の反応
Very hygroscopic. Water soluble.
反応プロフィール
Sensitive to hydrolysis, oxidation and heat. Incompatible with strong oxidizing agents. .
火災危険
Flash point data for Vincristine sulfate are not available; however, Vincristine sulfate is probably combustible.
生物活性
Anticancer agent; microtubule disrupter. Induces apoptosis in human lymphoma cells.
臨床応用
Vincristine sulfate is available as a 1-mg/mL solution in 1-,2-, and 5-mL vials for IV administration in acute leukemiaand as part of a multidrug regime for Hodgkin’s and neuroblastoma, Ewing sarcoma, Wilms tumor, soft tissuesarcoma, testicular cancer, liver cancer, and head and neckcancers. It has also been utilized in treating pediatric cancer.
代謝
Vincristine is metabolised in the liver by the cytochrome P450 isoenzymes CYP3A4 and CYP3A5 and excreted mainly in the bile; about 70-80 % of a dose is found in faeces, as unchanged drug and metabolites (40-50 %), while 10-20 % appears in the urine.
Vincristine is highly protein bound (75%) and may also bindto platelets that contain large amounts of tubulin. Numerousmetabolites have been detected and several have been identified,one of which is the 4-O-desacetyl derivative. The metabolismthat does occur is believed to largely be mediatedby CYP3A. Elimination occurs primarily in the bile with aterminal elimination half-life of 23 to 85 hours.
純化方法
The salt is recrystallised from MeOH. It has UV max at 220, 255 and 296nm (log 4.65, 4.21 and 4.18). It is a monoamine oxidase inhibitor and is used in cancer research [Son et al. J Med Chem 33 1845 1990, Horio et al. Proc Natl Acad Sci USA 85 3580 1988].
Mode of action
Vincristine Sulfate is the sulfate salt of a natural alkaloid isolated from the plant Catharanthus roseus (Vinca rosea L.) with antimitotic and antineoplastic activities. Vincristine binds irreversibly to microtubules and spindle proteins in S phase of the cell cycle and interferes with the formation of the mitotic spindle, thereby arresting tumor cells in metaphase. This agent also depolymerizes microtubules and may also interfere with amino acid, cyclic AMP, and glutathione metabolism; calmodulin-dependent Ca(2+)-activated ATPase activity; cellular respiration; and nucleic acid and lipid biosynthesis.
Toxicity evaluation
The mostcommonly seen toxicity for vincristine is a dose-limitingneurotoxicity caused by effects on axonal microtubules.Symptoms are variable and include peripheral neuropathy,ataxia, seizure, bone pain, and coma. Constipation is also acommonly seen toxicity, and laxatives may be used prophylactically.Other toxicities include alopecia, skin rash, mildmyelosuppression, secretion of antidiuretic hormone,azospermia, and amenorrhea.
ビンクリスチン硫酸塩 上流と下流の製品情報
原材料
準備製品