Amphotericin B trihydrate (amphotericin B trihydrate)

目录号: V34809 纯度: ≥98%
两性霉素 B 三水合物是一种多烯抗生素,最初从发酵菌株结节链霉菌中提取,具有抗利什曼原虫活性。
Amphotericin B trihydrate (amphotericin B trihydrate) CAS号: 1202017-46-6
产品类别: Bacterial
产品仅用于科学研究,不针对患者销售
规格 价格
500mg
1g
Other Sizes

Other Forms of Amphotericin B trihydrate (amphotericin B trihydrate):

  • Amphotericin B-13C6 (amphotericin B-13C6)
  • Amphotericin B methyl ester hydrochloride (盐酸两性霉素B甲酯)
  • 两性霉素B
点击了解更多
InvivoChem产品被CNS等顶刊论文引用
产品描述
两性霉素 B 三水合物是一种多烯抗生素,最初从发酵菌株结节链霉菌中提取,具有抗利什曼原虫活性。
生物活性&实验参考方法
靶点
Leishmania Plasmodium
体外研究 (In Vitro)
两性霉素 B 与胆固醇(哺乳动物细胞膜中发现的主要甾醇)相互作用,由于其相对较高的毒性而限制了该药物的实用性。在亚相中,两性霉素 B 以高度聚集的形式或以前胶束状态分布[4]。 B 仅在形成可渗透微小阳离子和阴离子的水孔时消除单细胞利什曼原虫前鞭毛体 (LP)。两性霉素 B (0.1 mM) 在负载 KCl 的脂质体中诱导极化电位,并悬浮在等渗蔗糖溶液中,表明 K+ 渗漏。当添加两性霉素 B (0.05 mM) 时,负膜电位几乎完全崩溃,显示 Na+ 渗透到细胞中[3]。
体内研究 (In Vivo)
在仓鼠痒病模型中,两性霉素 B 会延长潜伏期并减少 PrPSc 的积累。在患有传染性亚急性海绵状脑病 (TSSE) 的小鼠中,两性霉素 B 显着降低 PrPSc 水平[4]。 Amphotericin B 直接影响恶性疟原虫,并对寄生虫血症、鼠疟疾宿主存活以及受感染红细胞的红细胞凋亡产生影响。在感染伯氏疟原虫的小鼠中,两性霉素 B 往往会推迟寄生虫血症的发生,并大大推迟宿主死亡[5]。
药代性质 (ADME/PK)
Absorption, Distribution and Excretion
The pharmacokinetics of amphotericin B vary substantially depending on whether the drug is administered as conventional amphotericin B (formulated with sodium desoxycholate), amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, or amphotericin B liposomal, and pharmacokinetic parameters reported for one amphotericin B formulation should not be used to predict the pharmacokinetics of any other amphotericin B formulation.
Amphotericin B is poorly absorbed from the GI tract and must be given parenterally to treat systemic fungal infections. In one study, immediately after completion of iv infusion of 30 mg of amphotericin B (administered over a period of several hours), average peak serum concentrations were about 1 ug/ml; when the dose was 50 mg, average peak serum concentrations were approximately 2 ug/ml. Immediately after infusion, no more than 10% of the amphotericin B dose can be accounted for in serum. Average minimum serum concentrations (recorded just prior to the next drug infusion) of approximately 0.4 ug/ml have been reported when doses of 30 mg were given daily or when doses of 60 mg were given every other day.
Information on the distribution of amphotericin B is limited, although distribution is apparently multicompartmental. The volume of distribution of the drug following administration of conventional amphotericin B has been reported to be 4 L/kg; the volume of distribution at steady state after administration of amphotericin B cholesteryl sulfate is reported to be 3.8-4.1 L/kg. Amphotericin B concentrations attained in inflamed pleura, peritoneum, synovium, and aqueous humor following IV administration of conventional amphotericin B reportedly are about 60% of concurrent plasma concentrations; the drug also is distributed into vitreous humor, pleural, pericardial, peritoneal, and synovial fluid. Amphotericin B reportedly crosses the placenta and low concentrations are attained in amniotic fluid.
Following IV administration of conventional amphotericin B, CSF concentrations of the drug are approximately 3% of concurrent serum concentrations. To achieve fungistatic CSF concentrations, the drug must usually be administered intrathecally. In patients with meningitis, intrathecal administration of 0.2-0.3 mg of conventional amphotericin B via a subcutaneous reservoir has produced peak CSF concentrations of 0.5-0.8 ug/mL; 24 hours after the dose, CSF concentrations were 0.11-0.29 ug/mL. Amphotericin B is removed from the CSF by arachnoid villi and appears to be stored in the extracellular compartment of the brain, which may act as a reservoir for the drug.
For more Absorption, Distribution and Excretion (Complete) data for AMPHOTERICIN B (14 total), please visit the HSDB record page.
Biological Half-Life
Amphotericin B cholesteryl sulfate complex has a distribution half-life of 3.5 minutes and an elimination half-life of 27.5-28.2 hours. /Amphotericin B cholesteryl sulfate complex/
Following IV administration of conventional amphotericin B in patients whose renal function is normal prior to therapy, the initial plasma half-life is approximately 24 hours. After the first 24 hours, the rate at which amphotericin B is eliminated decreases and an elimination half-life of approximately 15 days has been reported.
Elimination, half life: Neonates: Variable (range, 18 to 62.5 hours). Children: Variable (range, 5.5 to 40.3 hours). Adults: Approximately 24 hours. Terminal half life: Approximately 15 days. NOTE: There is large interindividual variation among neonates in the elimination of amphotericin B. Amphotericin B may persist in the circulation of neonates for up to 17 days after it has been discontinued.
. The half life of elimination of amphotericin B from the lungs /of rats/ was 4.8 days according to serial sacrifices done after a single dose of 3.2 mg of aerosol doses of amphotericin B per kg.
毒性/毒理 (Toxicokinetics/TK)
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Although no information exists on the milk excretion of amphotericin B, it is highly protein bound, has a large molecular weight, is virtually unabsorbed orally and has been use directly in the mouths of infants; therefore, most reviewers consider it acceptable to use in nursing mothers.
◉ 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.
参考文献

[1]. Amphotericin B Appl Microbiol Biotechnol. 2005 Aug;68(2):151-62.

[2]. In-vitro and in-vivo antileishmanial activity of inexpensive Amphotericin B formulations: Heated Amphotericin B and Amphotericin B-loaded microemulsion. Exp Parasitol. 2018 Sep;192:85-92.

[3]. Amphotericin B kills unicellular leishmanias by forming aqueous pores permeable to small cations and anions. J Membr Biol. 1996 Jul;152(1):65-75.

[4]. Pharmacological studies of a new derivative of amphotericin B, MS-8209, in mouse and hamster scrapie. J Gen Virol. 1994 Sep;75 (Pt 9):2499-503.

[5]. Amphotericin B encapsulated in micelles based on poly(ethylene oxide)-block-poly(L-amino acid) derivatives exerts reduced in vitro hemolysis but maintains potent in vivo antifungal activity. Biomacromolecules. 2003 May-Jun;4(3):750-7.

其他信息
(1R,3S,5R,6R,9R,11R,15S,16R,17R,18S,33R,35S,36R,37S)-33-[(2R,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid has been reported in Trichoderma brevicompactum, Trichoderma virens, and other organisms with data available.
Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela.
See also: Amphotericin B (annotation moved to).
Mechanism of Action
Amphotericin B usually is fungistatic in action at concentrations obtained clinically, but may be fungicidal in high concentrations or against very susceptible organisms. Amphotericin B exerts its antifungal activity principally by binding to sterols (e.g., ergosterol) in the fungal cell membrane. As a result of this binding, the cell membrane is no longer able to function as a selective barrier and leakage of intracellular contents occurs. Cell death occurs in part as a result of permeability changes, but other mechanisms also may contribute to the in vivo antifungal effects of amphotericin B against some fungi. Amphotericin B is not active in vitro against organisms that do not contain sterols in their cell membranes (eg, bacteria).
Binding to sterols in mammalian cells (such as certain kidney cells and erythrocytes) may account for some of the toxicities reported with conventional amphotericin B therapy. At usual therapeutic concentrations of amphotericin B, the drug does not appear to hemolyze mature erythrocytes, and the anemia seen with conventional IV amphotericin B therapy may result from the action of the drug on actively metabolizing and dividing erythropoietic cells.
...Nephrotoxicity associated with conventional IV amphotericin B appears to involve several mechanisms, including a direct vasoconstrictive effect on renal arterioles that reduces glomerular and renal tubular blood flow and a lytic action on cholesterol-rich lysosomal membranes of renal tubular cells. ...
*注: 文献方法仅供参考, InvivoChem并未独立验证这些方法的准确性
化学信息 & 存储运输条件
分子式
C47H79NO20
分子量
978.12
CAS号
1202017-46-6
相关CAS号
Amphotericin B;1397-89-3;Amphotericin B-13C6
PubChem CID
14956
外观&性状
Deep yellow prisms or needles from n,n-dimethylformamide
YELLOW TO ORANGE POWDER
熔点
170 °C (gradual decomposition)
氢键供体(HBD)数目
12
氢键受体(HBA)数目
18
可旋转键数目(RBC)
3
重原子数目
65
分子复杂度/Complexity
1670
定义原子立体中心数目
19
HS Tariff Code
2934.99.9001
存储方式

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

运输条件
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
溶解度数据
溶解度 (体外实验)
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
溶解度 (体内实验)
注意: 如下所列的是一些常用的体内动物实验溶解配方,主要用于溶解难溶或不溶于水的产品(水溶度<1 mg/mL)。 建议您先取少量样品进行尝试,如该配方可行,再根据实验需求增加样品量。

注射用配方
(IP/IV/IM/SC等)
注射用配方1: DMSO : Tween 80: Saline = 10 : 5 : 85 (如: 100 μL DMSO 50 μL Tween 80 850 μL Saline)
*生理盐水/Saline的制备:将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中,得到澄清溶液。
注射用配方 2: DMSO : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (如: 100 μL DMSO 400 μL PEG300 50 μL Tween 80 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如: 100 μL DMSO 900 μL Corn oil)
示例: 注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液,加到 900 μL Corn oil/玉米油中, 混合均匀。
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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如:100 μL DMSO 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备(4°C,储存1周):将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中,得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如: 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精) 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如: 50 μL DMSO 100 μL PEG300 200 μL Castor oil 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (如: 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如: 100 μL EtOH 900 μL Corn oil)
注射用配方 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (如: 100 μL EtOH 400 μL PEG300 50 μL Tween 80 450 μL Saline)


口服配方
口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中,得到0.5%CMC-Na澄清溶液;然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中,得到悬浮液。
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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合


注意: 以上为较为常见方法,仅供参考, InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型,对于某些尚未有文献报道溶解方法的化合物,需通过前期实验来确定(建议先取少量样品进行尝试),包括产品的溶解情况、梯度设置、动物的耐受性等。

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。
制备储备液 1 mg 5 mg 10 mg
1 mM 1.0224 mL 5.1118 mL 10.2237 mL
5 mM 0.2045 mL 1.0224 mL 2.0447 mL
10 mM 0.1022 mL 0.5112 mL 1.0224 mL

1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;

2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;

3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);

4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。

计算器

摩尔浓度计算器可计算特定溶液所需的质量、体积/浓度,具体如下:

  • 计算制备已知体积和浓度的溶液所需的化合物的质量
  • 计算将已知质量的化合物溶解到所需浓度所需的溶液体积
  • 计算特定体积中已知质量的化合物产生的溶液的浓度
使用摩尔浓度计算器计算摩尔浓度的示例如下所示:
假如化合物的分子量为350.26 g/mol,在5mL DMSO中制备10mM储备液所需的化合物的质量是多少?
  • 在分子量(MW)框中输入350.26
  • 在“浓度”框中输入10,然后选择正确的单位(mM)
  • 在“体积”框中输入5,然后选择正确的单位(mL)
  • 单击“计算”按钮
  • 答案17.513 mg出现在“质量”框中。以类似的方式,您可以计算体积和浓度。

稀释计算器可计算如何稀释已知浓度的储备液。例如,可以输入C1、C2和V2来计算V1,具体如下:

制备25毫升25μM溶液需要多少体积的10 mM储备溶液?
使用方程式C1V1=C2V2,其中C1=10mM,C2=25μM,V2=25 ml,V1未知:
  • 在C1框中输入10,然后选择正确的单位(mM)
  • 在C2框中输入25,然后选择正确的单位(μM)
  • 在V2框中输入25,然后选择正确的单位(mL)
  • 单击“计算”按钮
  • 答案62.5μL(0.1 ml)出现在V1框中
g/mol

分子量计算器可计算化合物的分子量 (摩尔质量)和元素组成,具体如下:

注:化学分子式大小写敏感:C12H18N3O4  c12h18n3o4
计算化合物摩尔质量(分子量)的说明:
  • 要计算化合物的分子量 (摩尔质量),请输入化学/分子式,然后单击“计算”按钮。
分子质量、分子量、摩尔质量和摩尔量的定义:
  • 分子质量(或分子量)是一种物质的一个分子的质量,用统一的原子质量单位(u)表示。(1u等于碳-12中一个原子质量的1/12)
  • 摩尔质量(摩尔重量)是一摩尔物质的质量,以g/mol表示。
/

配液计算器可计算将特定质量的产品配成特定浓度所需的溶剂体积 (配液体积)

  • 输入试剂的质量、所需的配液浓度以及正确的单位
  • 单击“计算”按钮
  • 答案显示在体积框中
动物体内实验配方计算器(澄清溶液)
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
第二步:请输入动物体内配方组成(配方适用于不溶/难溶于水的化合物),不同的产品和批次配方组成不同,如对配方有疑问,可先联系我们提供正确的体内实验配方。此外,请注意这只是一个配方计算器,而不是特定产品的确切配方。
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计算结果:

工作液浓度 mg/mL;

DMSO母液配制方法 mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。

体内配方配制方法μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL ddH2O,混匀澄清。

(1) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
            (2) 一定要按顺序加入溶剂 (助溶剂) 。

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