ナイスタチン

解説

C47H75NO17(926.11)．Streptomyces nourseiやその他の放線菌の培養液から単離されるポリエン系抗生物質．白色～淡黄色の結晶．160 ℃ から徐々に，250 ℃ までに分解する．[α]²⁵_D＋21°(ピリジン)．λmax 290，307，322 nm(エタノール)．水，エタノールに難溶，DMFに可溶．熱，光，空気に不安定である．酸，アルカリにより分解される．抗真菌剤で消化管カンジダ症治療薬として使用される．LD50  ＞ 9000 mg/kg(マウス，経口)．森北出版「化学辞典（第2版）

用途

細胞生物学の研究では、ナイスタチンは哺乳動物細胞の脂質ラフトカベオラ（英語版）エンドサイトーシス経路の阻害剤として、3μg/mL前後の濃度で使用されている。 特定の場合、ナイスタチンは美術品の防黴に応用される。 ナイスタチンは電気生理学の分野では細胞の穿孔パッチクランプ記録法に利用される。

用途

ナイスタチンは，マイコスタチンともいう。真菌症治療用抗生物質である。クリプトコッカス，ヒストプラスマ，ブラストマイセスなどに対し，1.5～6.5 μg/ml で効力を示す。耐薬性は通常みられない。消化管，皮膚，粘膜から吸収されないので，局所に適用する。経口投与では，副作用として胃腸障害，過敏症状がみられることがある。

効能

抗生物質, 抗真菌薬

説明

Nystatin was found in the mycelium of Streptomyces noursei in 1950 and produced on an industrial scale by Squibb & Sons Co. in 1954. This antibiotic was used orally and topically as the first clinically applied polyene macrolide with antifungal properties. Nystatin shows activity against Candida and filamentous fungi and is used to treat Candida infections of the mouth, digestive organs, and vagina. The application of nystatin in combination with gentamicin and vancomycin to sterilize the gut in perioperation of bone-marrow transplantation has been developed recently.

化学的特性

This substance is a yellow or yellow-brown powder with a unique smell and the ability to absorb moisture. It dissolves to a small extent in water, methanol, and ethanol, but cannot dissolve in acetone, ether, or chloroform. It is not stable when exposed to air, light, heat, water, acid, or alkali.

使用

Polyene antifungal antibiotic complex containing 3 biologically active components, A1, A2, A3. Increases the permeability of the cell membrane of sensitive fungi by binding to sterols. Cell culture tested. Growth promotant. Nystatin A1 is shown.

定義

ChEBI: A polyene macrolide antibiotic; part of the nystatin complex produced by several Streptococcus species. The keto-form of nystatin A1.

適応症

Nystatin (Mycostatin) is a polyene antifungal drug with a ring structure similar to that of amphotericin B and a mechanism of action identical to that of amphotericin B. Too toxic for systemic use, nystatin is limited to the topical treatment of superficial infections caused by C. albicans. Infections commonly treated by this drug include oral candidiasis (thrush), mild esophageal candidiasis, and vaginitis.

一般的な説明

Nystatin (Mycostatin) is a polyene antibiotic that was first isolated in 1951 from a strain of the actinomycete Streptomyces noursei by Hazen and Brown.33 It occurs as a yellow to light tan powder. Nystatin is very slightly soluble in water and sparingly soluble in organic solvents. The compound is unstable to moisture, heat, and light. The aglycone portion of nystatin is called nystatinolide. The complete structure of nystatin has been determined by chemical degradation and x-ray crystallography.35 Nystatin is not absorbed systemically when administered by the oral route. It is nearly insoluble under all conditions. It is also too toxic to be administered parenterally. Hence, it is used only as a topical agent. Nystatin is a valuable agent for the treatment of local and gastrointestinal monilial infections caused by C. albicans and other Candida species. For the treatment of cutaneous and mucocutaneous candidiasis, it is supplied as a cream, an ointment, and a powder. Vaginal tablets are available for the control of vaginal candidiasis. Oral tablets and troches are used in the treatment of gastrointestinal and oral candidiasis. Combinations of nystatin with tetracycline can be used to prevent monilial overgrowth caused by the destruction of bacterial microflora of the intestine during tetracycline therapy.

薬理学

Nystatin is stereoisomeric 33-[(3-amino-3,6-dideoxy-β-D-mannopyranosyl) oxy]-1,3,4,7,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo [33.3.1] nonatriaconta-19,21,25,27,29,31-hexaen-36-carboxylic acid (35.1.2). Nystatin was isolated in 1949 from the products of the vital activity of the actinomycete Streptomyces noursei, and it was the first antifungal antibiotic to be discovered. This polyene antibiotic is structurally similar to amphotericin B. It has a broad spectrum of activity. The mechanism of antifungal activity is similar to the mechanism of action of amphotericin B. It is used for preventing and treating candida infections of the skin and mucous membranes. In terms of preventative action, it is used for preventing the development of candidomycosis during prolonged treatment with penicillin drugs and antibiotics of other group, especially during oral use of tetracycline antibiotics, levomecytin, and others. Synonyms of this drug are biofanal, moronal, nicporil, fazigin, candex, and others.

臨床応用

Nystatin, the first clinically useful polyene antifungal antibiotic, is a conjugated tetraene isolated from cultures of the bacterium Streptomyces noursei in 1951. Nystatin is an effective topical antifungal against a wide variety of organisms and is available in a variety of creams and ointments. Nystatin is too toxic to be used systemically, but because very little drug is absorbed following oral administration, it may be administered by mouth to treat fungal infections of the mouth and gastrointestinal tract.

安全性プロファイル

Poison by intraperitoneal and intravenous routes. Moderately toxic by subcutaneous route. Mildly toxic by ingestion. An experimental teratogen. Mutation data reported. An antibiotic. When heated to decomposition it emits toxic fumes of NOx.

純化方法

Nystatin is a light yellow powder with the following solubilities at ~28o: MeOH (1.1%), ethylene glycol (0.9%), H2O (0.4%), CCl4 (0.12%), EtOH (0.12%), CHCl3 (0.05%) and *C6H6 (0.03%). It has been precipitated from MeOH solution by addition of H2O. Aqueous suspensions of this macrolide antifungal antibiotic are stable at 100o/10minutes at pH 7.0 but decompose rapidly at pH <2 and >9, and in the presence of light and O2. [Birch et al. Tetrahedron Lett 1491, 1485 1964, Weiss et al. Antibiot Chemother 7 374 1957.] It may contain a mixture of components A1, A2 and A3. [Beilstein 18 III/IV 7480.]