Nystatin   中文名称: 制霉菌素

Anti-fungal

制霉菌素（Candex；Mycostatin；Barstatin 100；Biofanal；AI3-26526）可显着减少所有六种念珠菌属的颊上皮细胞粘附[1]。制霉菌素是一种抗生素，可增加质膜对小单价离子（包括氯离子）的渗透性。制霉菌素将顶端氯离子通透性增加至跨上皮氯离子转运受到穿过气管上皮细胞基底外侧膜的转运的限制，这主要反映了协同转运蛋白的活性。制霉菌素 (400 单位/mL) 使跨上皮 36Cl 通量的基础水平增加约 1.5 倍，并消除该通量的 UTP 刺激。制霉菌素治疗还消除了 UTP 对可饱和基底外侧 [3H] 布美他尼结合的刺激，这是这些细胞中 Na-K-Cl 协同转运蛋白功能的衡量标准。制霉菌素治疗仅轻度抑制异丙肾上腺素结合刺激[2]。制霉菌素通过将内皮抑素内化主要转变为网格蛋白介导的途径，显着增强内皮细胞对内皮抑素的摄取。制霉菌素增强内皮抑素的内化也增加了其对内皮细胞管形成和迁移的抑制作用[3]。

制霉菌素 (Candex;Mycostatin; Barstatin 100; Biofanal; AI3-26526) 与内皮抑素联合选择性增强内皮抑素在肿瘤血管和肿瘤组织中的摄取和生物分布，但不在荷瘤小鼠的正常组织中，最终提高抗血管生成和抗肿瘤功效体内内皮抑素的研究[3]。脂质体制霉菌素，剂量低至 2 毫克/公斤体重/天，与不治疗、生理盐水或生理盐水治疗组相比，在 50 天时间点以统计学上显着的方式保护中性粒细胞减少小鼠免受曲霉菌诱导的死亡。空脂质体组[4]。

Absorption, Distribution and Excretion
Systemic absorption of nystatin is minimal following oral administration, and no detectable plasma concentrations are attained following topical or vaginal administration.
The majority of orally administered nystatin is eliminated unchanged in the feces.
Nystatin is not absorbed into the systemic circulation and thus does not undergo distribution.
Nystatin penetrates eye poorly.
Nystatin is poorly absorbed from the GI tract, and detectable blood concentrations are not obtained after usual doses. Following oral administration, nystatin is excreted almost entirely in feces as unchanged drug.
In healthy individuals, mean salivary nystatin concentrations in excess of those required in vitro for growth inhibition of clinically important Candida persist for approximately 2 hours after the beginning of oral dissolution of two nystatin lozenges (400,000 units) administered simultaneously.
Not absorbed following topical application to intact skin or mucous membranes.
For more Absorption, Distribution and Excretion (Complete) data for NYSTATIN (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
Because nystatin undergoes little-to-no systemic absorption it is not metabolized to any appreciable extent.

Hepatotoxicity
Nystatin therapy has been associated with a low rate of serum enzyme abnormalities, although it has been difficult to attribute these elevations to nystatin. Despite its use for several decades, there have been no convincing cases of acute hepatic injury linked to nystatin therapy. While nystatin is usually is not normally absorbed, low concentrations may enter the circulation in patients with inflammation and damage to the gastrointestinal tract. Nevertheless, nystatin is considered very safe and is unlikely to cause hepatic injury.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Although no information exists on the milk excretion of nystatin, it is virtually unabsorbed orally, therefore most reviewers and clinicians consider it acceptable for use in nursing mothers, including topical application to the nipples. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking. Any excess cream should be removed from the nipples before nursing. Nystatin is less effective than other topical agents for the treatment of thrush.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Nystatin is not absorbed into the systemic circulation and is therefore not subject to plasma protein binding.

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Non-Human Toxicity Values
LD50 Mouse ip 200 mg/kg

[1]. Adhesion of oral Candida species to human buccal epithelial cells following brief exposure to nystatin. Oral Microbiol Immunol. 1999 Dec;14(6):358-63.

[2]. Na-K-Cl cotransport in nystatin-treated tracheal cells: regulation by isoproterenol, apical UTP, and [Cl]i. Am J Physiol. 1994 May;266(5 Pt 1):C1440-52.

[3]. Cholesterol sequestration by nystatin enhances the uptake and activity of endostatin in endothelium via regulating distinct endocytic pathways. Blood. 2011 Jun 9;117(23):6392-403.

[4]. Activity of liposomal nystatin against disseminated Aspergillus fumigatus infection in neutropenic mice. Antimicrob Agents Chemother. 1997 Oct;41(10):2238-43.

[5]. Oxaliplatin enhances TRAIL-induced apoptosis in gastric cancer cells by CBL-regulated death receptor redistribution in lipid rafts.FEBS Lett. 2009 Mar 4;583(5):943-8.

Therapeutic Uses
Antibiotics, Antifungal; Antibiotics, Macrolide; Ionophores
MEDICATION (VET):Antifungal; growth promotant
MEDICATION (VET): /Used in treatment of/ intestinal mycosis due to Candida albicans in poultry; occasionally orally in cats and dogs in suspected Candida intestinal overgrowth following antibiotic therapy, and also topically ... as cream or ointment on skin lesions ...
Nystatin vaginal tablets are used as lozenges to treat oropharyngeal candidiasis since their slow dissolution rate provides prolonged oral contact. /NOT included in US product labeling/
For more Therapeutic Uses (Complete) data for NYSTATIN (9 total), please visit the HSDB record page.

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Drug Warnings
Since it is not known whether nystatin is distributed into human milk, the drug should be used with caution in nursing women.
Adverse effects occur infrequently with oral nystatin therapy. Mild and transitory nausea, vomiting, GI distress, and diarrhea have occurred; high oral doses (e.g., greater than 5 million units daily) are most likely to produce these adverse GI effects. Hypersensitivity reactions have been reported very rarely.
Patients should be instructed to contact their physician if symptoms of irritation or sensitization occur during nystatin therapy. Patients should be warned against interrupting or discontinuing vaginal nystatin therapy during a prescribed regimen, even during menstruation or if symptomatic relief occurs after only a few days of therapy, unless otherwise instructed by their physician. Patients should be advised that adjunctive measures such as therapeutic douches are not necessary and may be inadvisable during vaginal nystatin therapy; however, cleansing douches may be used in nonpregnant women, if desired, for aesthetic effect.
Adverse reactions to topically applied nystatin are very infrequent, even during prolonged use. Irritation has occurred rarely. Hypersensitivity reactions to nystatin have been reported only rarely; however, preservatives (eg, ethylenediamine, parabens, thimerosal) in some of the formulations are associated with a high incidence of contact dermatitis. An acneiform eruption has occurred rarely following topical application of nystatin and triamcinolone acetonide.
For more Drug Warnings (Complete) data for NYSTATIN (9 total), please visit the HSDB record page.

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Pharmacodynamics
Nystatin is an antifungal that is both fungistatic and fungicidal in vitro against a wide variety of yeasts and yeast-like fungi. It exerts its antifungal effects via disruption of the fungal cell membrane. Resistance to nystatin is minimal in _Candida albicans_, but tends to develop in other species of _Candida_. Nystatin carries no significant activity against bacteria, protozoa, or viruses. It carries significant systemic toxicity and is currently unavailable in a formula appropriate for systemic use - its efficacy is currently restricted, therefore, to topical, oral, and gastrointestinal infections.

C47H75NO17

926.110

276.208

C, 60.96; H, 8.16; N, 1.51; O, 29.37

1400-61-9

11286230

Light yellow to khaki solid powder

0.9±0.1 g/cm3

400.2±14.0 °C at 760 mmHg

>155°C (dec.)

297.0±15.2 °C

0.0±2.0 mmHg at 25°C

1.504

6.14

327.45

12

18

3

65

1620

19

O1C2([H])C([H])([H])C([H])(C([H])=C([H])C([H])=C([H])C([H])=C([H])C([H])=C([H])C([H])([H])C([H])([H])C([H])=C([H])C([H])=C([H])[C@@]([H])(C([H])([H])[H])[C@@]([H])([C@]([H])(C([H])([H])[H])[C@@]([H])(C([H])([H])[H])OC(C([H])([H])C([H])(C([H])([H])C([H])(C([H])([H])C([H])(C([H])([H])C([H])([H])C([H])(C([H])(C([H])([H])[C@]1(C([H])([H])C([H])(C2([H])C(=O)O[H])O[H])O[H])O[H])O[H])O[H])O[H])O[H])=O)O[H])O[C@@]1([H])[C@@]([H])([C@@]([H])([C@]([H])([C@]([H])(C([H])([H])[H])O1)O[H])N([H])[H])O[H] |c:9,13,17,21,31,35|

VQOXZBDYSJBXMA-JKMCSYCMSA-N

InChI=1S/C47H75NO17/c1-27-17-15-13-11-9-7-5-6-8-10-12-14-16-18-34(64-46-44(58)41(48)43(57)30(4)63-46)24-38-40(45(59)60)37(54)26-47(61,65-38)25-36(53)35(52)20-19-31(49)21-32(50)22-33(51)23-39(55)62-29(3)28(2)42(27)56/h5-6,8,10-18,27-38,40-44,46,49-54,56-58,61H,7,9,19-26,48H2,1-4H3,(H,59,60)/b6-5-,10-8+,13-11+,14-12+,17-15+,18-16+/t27-,28-,29-,30+,31+,32+,33-,34+,35+,36-,37-,38-,40-,41-,42+,43+,44-,46+,47+/m0/s1

(1S,3S,4R,7R,9R,11S,15S,16R,17R,18S,19E,21E,25Z,27E,29E,31E,33S,35S,36S,37S)-33-(((2S,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyltetrahydro-2H-pyran-2-yl)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-hexaene-36-carboxylic acid

Nystatin; Mycostatin. AI3-26526; Barstatin 100; Biofanal; Candex; Candex Lotion; Candio-hermal; Diastatin; Fungicidin; Herniocid; HSDB 3138; Korostatin; Moronal; Myconystatin; Mycostatin; Nilstat; Nistatin; Nistatina; NSC 150817; Nyamyc; Nyotran; Nysert; Nystan; Nystatin; Nystatine; Nystavescent; Nystex; Nystop; O-V Statin; Stamycin; Zydin E

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： (1). 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮和光照。  (2). 该产品在溶液状态不稳定，请现配现用。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~53.99 mM)

配方 1 中的溶解度: 2.5 mg/mL (2.70 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浮液；超声助溶。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (2.70 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (2.70 mM) (饱和度未知) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。