G551D-CFTR (EC50: 100 nM), F508del-CFTR (EC50: 25 nM)

Ivacaftor (10 µM) 使 ABCB4-G535D 的 PC 分泌活性增强 3 倍，对于 ABCB4-G536R 增强 13.7 倍，对于 ABCB4-S1076C 增强 6.7 倍，对于 ABCB4-S1176L 增强 9.4 倍，对于 ABCB4-G1178S 增强 5.7 倍。 Ivacaftor 修复了 ABCB4 突变体的功能缺陷[1]。与 R1162X CFTR 细胞相比，Ivacaftor (10 μM) 显着增强 W1282X 表达细胞中的 CFTR 活性[2]。尽管测试了 160 个靶点，包括 GABAA 苯二氮卓类药物，ivacaftor 没有表现出明显的活性。与 F508del HBE 相比，ivacaftor 的效力变化了 10 倍，增加了氯离子分泌，EC50 为 0.236 ± 0.200 μM[3]。 VX-770 提高重组细胞中 G551D 门控突变和 F508del 加工突变的 CFTR 通道开放概率 (Po)。在 EC50 为 25 nM 时，VX-770 在温度校正的 F508del-FRT 细胞中将毛喉素刺激的 IT 增强约 6 倍[4]。

在大鼠中，Ivacaftor（100–200 mg/kg，口服）具有良好的口服生物利用度[3]。 在一项大鼠剂量比例研究中，以1至200mg/kg的剂量在悬浮液中口服（VX-770，ivacaftor）后，AUC和Cmax呈线性增加（3、10、30和100为中等剂量）。在比格犬中观察到类似的趋势，将口服剂量从3 mg/kg增加到80 mg/kg（10、30和60为中等剂量），证实了高水平的口服吸收。 使用四种物种的异速生长标度法预测的（VX-770，ivacaftor）的人体肝脏清除率为4.7 mL min-1 kg-1，约占肝血流量的23%。基于其效力、选择性和良好的药代动力学特征，化合物48（VX-770，ivacaftor）被选为进一步的（预）临床评估，并最终被美国食品药品监督管理局批准用于治疗携带G551D突变的6岁及以上CF患者。[3]

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囊性纤维化跨膜电导调节因子（CFTR）基因中的过早终止密码子（PTCs）导致CFTR蛋白无功能，是约11%CF致病等位基因的直接原因。众所周知，氨基糖苷和其他新型药物可以诱导PTCs的翻译再通，这是一种潜在的治疗方法。在PTCs中，W1282X CFTR是独一无二的，因为它是一种C末端CFTR突变，即使在截短状态下也能表现出部分活性。增效剂（VX-770）已被批准用于治疗G551D和其他门控突变的CF患者。基于先前的研究证明了ivacaftor对体外再通后PTC突变的有益作用，我们假设ivacaftor可能会增强表达W1282X CFTR的CF患者的CFTR活性，并且可以通过再通进一步增强。与R1162X CFTR细胞相比，Ivacaftor显著增加了W1282X表达细胞中的CFTR活性，并且通过氨基糖苷类G418的读取进一步增强。来自W1282X纯合子患者的原代鼻上皮细胞在ivacaftor (VX-770)存在下显示出CFTR功能的改善。同一患者服用依伐他汀后，肺部加重频率、BMI和胰岛素需求量显著改善，而FEV1在3年内保持稳定。这些研究表明，ivacaftor可能通过刺激截短蛋白的残余活性，对W1282X CFTR突变表达保持的患者具有中度临床益处，这表明需要进一步研究，包括添加有效的readthrough药物[2]。

用于检测F508del CFTR增效剂活性的膜电位光学测定法[3] 为了鉴定F508del CFTR的增效剂，使用FLIPR III荧光板读取器开发了利用荧光电压传感探针的HTS测定格式。将稳定表达F508del CFTR的NIH-3T3细胞在27°C下孵育16-24小时，以纠正错误折叠的F508del CF TR。然后用浴溶液（160mM NaCl、4.5mM KCl、2mM CaCl2、1mM MgCl2、10mM HEPES，用NaOH的pH 7.4）洗涤细胞，并用与测试化合物（或DMSO载体对照）组合的荧光电压传感染料在室温下处理30分钟。该测定在FLIPR III上进行，使用含有毛喉素的无Cl浴溶液的单一液体添加步骤。检测到的膜电位变化是由于测试化合物对通过F508del CFTR的Cl–阴离子通量的增效剂活性。

Ussing Chamber Recordings[3]
除非另有说明，否则在记录之前，所有细胞都生长在保持在37°C的Costar Snapwell细胞培养插入物上。将细胞培养插入物安装到Using室（VCC MC8）中，以在电压钳模式（Vhold＝0mV）下记录ISC。为了测量ISC，基底外侧浴溶液含有以下物质（以mM为单位）：135 NaCl、1.2 CaCl2、1.2 MgCl2、2.4 K2HPO4、0.6 KH2PO4、10 N-2-羟乙基哌嗪-N′-2-乙磺酸（HEPES）和10葡萄糖（用NaOH滴定至pH 7.4）。用等摩尔Na+葡萄糖酸盐（用NaOH滴定至pH 7.4）代替顶端的NaCl。对于HBE细胞，在存在基底外侧至顶端Cl–梯度的情况下测量ISC。正常Cl–溶液含有以下物质（单位：mM）：145 NaCl、0.83 K2HPO4、3.3 KH2PO4、1.2 MgCl2、1.2 CaCl2、10葡萄糖、10 HEPES（用NaOH将pH调节至7.35）。低Cl–溶液含有以下物质（单位：mM）：145葡萄糖酸钠、1.2 MgCl2、1.2 CaCl2、10葡萄糖、10 HEPES（用NaOH将pH调节至7.35）。ISC是使用获取和分析软件以数字方式获取的。[3]
cAMP测量[3]

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施用测试化合物后FRT细胞中的总cAMP浓度（细胞和分泌的）根据制造商指示使用cAMP Screen 96孔免疫测定系统测定。简言之，将FRT细胞与测试化合物一起孵育15分钟，然后裂解并转移到提供有试剂盒的96孔测定板上。将板在室温下孵育1小时，之后将其显影，并使用LJL Biosystems的Acquest 384.1536测量发光。使用存在于每个平板中的cAMP标准曲线来测定cAMP浓度。

In Vivo Pharmacokinetic Experiments [3]
Male mouse, Sprague–Dawley rats, beagle dog, and cynomolgus monkeys (n = 3/group) were administered a single iv dose of compound formulated in dimethyl isosorbide/ethanol/PEG400/5% dextrose in water (D5W) (10%/15%/35%/40%) at the nominal dose indicated in a dose volume of 1 mL/kg. Blood samples (0.3 mL, sodium heparin anticoagulant) were collected from an indwelling carotid cannula at the following nominal time points: at predose, 5, 15, 30, and 45 min and 1, 2, 4, 6, 8, 12, 24, 36, and 48 h following iv administration and at predose, 0.25, 0.50, 1, 1.5, 2, 4, 8, 12, and 24 h following oral administration. The concentration of compound in the plasma samples was determined with a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method, which had a lowest limit of quantitation (LLOQ) of 1 ng/mL and a linearity range between 1 and 2500 ng/mL. The mean plasma concentration–time profiles and the measured dose values were used to estimate the pharmacokinetic parameters using noncompartmental analysis modules in WinNonlin Professional Edition software, version 4.0.1.

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1-200 mg/kg, p.o.

Rats

Ivacaftor is well absorbed in the gastrointestinal tract. Following administration of ivacaftor with fat-containing foods, peak plasma concentrations were reached at 4 hours (Tmax) with a maximum concentration (Cmax) of 768 ng/mL and AUC of 10600 ng * hr/mL. It is recommended that ivacaftor is taken with fat-containing foods as they increase absorption by approximately 2.5- to 4-fold.
After oral administration, ivacaftor is mainly eliminated in the feces after metabolic conversion and this elimination represents 87.8% of the dose. From the total eliminated dose, the metabolites M1 and M6 account for the majority of the eliminated dose, being 22% for M1 and 43% for M6. Ivacaftor shows negligible urinary excretion as the unchanged drug.
After oral administration of 150 mg every 12 hours for 7 days to healthy volunteers in a fed state, the mean (±SD) for apparent volume of distribution was 353 (122) L.
The CL/F (SD) for the 150 mg dose was 17.3 (8.4) L/hr in healthy subjects.

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Ivacaftor is extensively metabolized in humans. In vitro and clinical studies indicate that ivacaftor is primarily metabolized by CYP3A. From this metabolism, the major formed metabolites are M1 and M6. M1 is considered pharmacologically active even though it just presents approximately one-sixth the effect of the parent compound ivacaftor. On the other hand, M6 is not considered pharmacologically active as it represents less than one-fiftieth of the effect of the parent compound.

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In a clinical study, the apparent terminal half-life was approximately 12 hours following a single dose of ivacaftor. One source mentions the half-life ranges from 12 to 14 hours.

◉ Summary of Use during Lactation
Maternal ivacaftor therapy produce low levels in milk and very low levels in the serum of breastfed infants. An international survey of cystic fibrosis centers found no adverse effects in breastfed infants of mothers taking these drugs and a task force respiratory experts from Europe, Australia and New Zealand found that these drugs are probably safe during breastfeeding. One breastfed infant had transient elevations in bilirubin and liver enzymes during maternal therapy that could not definitively be attributed to the drugs in breastmilk. Until more data are available, monitoring of infant bilirubin and liver enzymes might be advisable during breastfeeding with maternal ivacaftor therapy. Congenital cataracts in breastfed infants has been reported in the infants of mothers who took the drug during pregnancy, so examination of breastfed infants for cataracts has been recommended. Anecdotal evidence indicates that the drugs in breastmilk may moderate cystic fibrosis in breastfed infants.
◉ Effects in Breastfed Infants
A woman with cystic fibrosis was treated with lumacaftor and ivacaftor during pregnancy and postpartum. Her infant was fully breastfed until day 29 postpartum when elevated direct and indirect bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase were found to be elevated. All values had been normal on days 1 and 14. The fraction of breastmilk the infant received was reduced to 25% and all values were normal on day 37. The fraction of breastfeeding was increased to 50% and then to 100%. On day 135, the infant's direct bilirubin was elevated during concurrent maternal levofloxacin and trimethoprim-sulfamethoxazole therapy. The fraction of breastfeeding was decreased to 75% and the direct bilirubin was normal on day 154. The authors noted that the abnormal test results could not definitively be attributed to lumacaftor and ivacaftor therapy.
A survey was sent to lead clinicians of adult CF centers in Europe, the United Kingdom, United States of America, Australia and Israel requesting anonymized data on pregnancy outcomes in women using CFTR modulators during pregnancy and lactation. Responses were received from 31 centers and one woman with CF for a total of 64 pregnancies in 61 women resulting in 60 live births. Thirteen infants were breastfed on ivacaftor alone, 9 infants were breastfed on lumacaftor and ivacaftor, and 5 infants were breastfed on tezacaftor and ivacaftor for a total of 27 infants exposed to ivacaftor in breastmilk, all with no reported complications. The extent of breastfeeding was not reported. An updated survey by the same authors asked CF clinicians to report on pregnant women exposed to the elexacaftor, tezacaftor and ivacaftor combination during pregnancy and breastfeeding. Twenty-six infants were breastfed (extent not stated) during maternal use of the combination. No adverse effects were reported in the breastfed infants.
An infant was born to a mother taking elexacaftor, ivacaftor and tezacaftor for cystic fibrosis. The infant was breastfed (extent not stated). Although the infant had cystic fibrosis-causing CFTR mutations, the infant was healthy and tested negative for cystic fibrosis on newborn screening. The authors expressed concern that the drugs received transplacentally and in breastmilk caused a false negative screening test.
A mother who was a heterozygous carrier of the F508del gene became pregnant with a homozygous infant. At 32 weeks of pregnancy, the mother began elexacaftor, ivacaftor and tezacaftor in the usual adult dosage to treat her fetus who had evidence of meconium ileus. The infant was born at 36 weeks and given pancreatic enzyme replacement therapy with breastfeeding while maternal treatment continued. The infant’s fecal elastase, transaminases and bilirubin were normal at about 1 month of age. The infant’s sweat chloride, although low, was nearer to normal than was expected. The authors hypothesized that the medications received in breastmilk moderated the disease process in the infant.
Three women with cystic fibrosis were taking elexacaftor, ivacaftor and tezacaftor in unspecified dosages during pregnancy and postpartum while breastfeeding. On routine visual examinations between 8 days and 6 months postpartum, their infants were found to have small (<1.0 mm) bilateral cataracts, in the central area in one and outside the visual axis in the other two. Breastfeeding was discontinued after diagnosis at 16 days, 9 weeks and 6 months postpartum. The contribution of breastfeeding to the cataracts could not be determined.
Two women were reported by the British Columbia cystic fibrosis clinic who became pregnant and breastfed their infants. One took ivacaftor and breastfed (extent not stated) for 42 months. Her infant was physically normal and healthy, but had speech delay. The other woman took Tricafta (ivacaftor, elexacaftor, and tezacaftor). She breastfed (extent not stated) her infant for 6 months and her infant had no complications.
A woman with cystic fibrosis took ivacaftor 150 mg, tezacaftor 100 mg and elexacaftor 200 mg in the morning and ivacaftor 150 mg at night during pregnancy and breastfeeding (extent not stated). The infant had not regained his birthweight at 10 days postpartum, his stools had a greasy rim and he had pancreatic elastase levels below levels for pancreatic sufficiency but higher than usually expected for newborns homozygous for this mutation. The infant was started on pancreatic enzymes and by day 20, he had normal elastase levels. By day 45 of life was gaining weight and stools were normal. At 6 months of age the infant was still being breastfed and doing well. The authors felt that when breastfeeding is stopped, a rebound in symptoms might occur because the infant will no longer be receiving small amounts of the mother’s medications through milk.
A woman with cystic fibrosis received elexacaftor 100 mg, tezacaftor, 50 mg, ivacaftor 75 mg and additional ivacaftor 150 mg daily from 12 weeks of pregnancy and postpartum. The mother exclusively breastfed her infant while continuing therapy, and no significant side effects related were observed in the infant up to at least 3 months of age.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.hrAbout 99% of ivacaftor is bound to plasma proteins, primarily to alpha 1-acid glycoprotein and albumin.

[1]. Functional defect of variants in the adenosine triphosphate-binding sites of ABCB4 and their rescue by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770). Hepatology. 2017 Feb;65(2):560-570.

[2]. Therapeutic benefit observed with the CFTR potentiator, ivacaftor, in a CF patient homozygous for the W1282X CFTR nonsense mutation. J Cyst Fibros. 2017 Jan;16(1):24-29.

[3]. Discovery of N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, ivacaftor), a potent and orally bioavailable CFTR potentiator. J Med Chem. 2014 Dec 11;57(23):9776-9.

[4]. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18825-30.

Ivacaftor is an aromatic amide obtained by formal condensation of the carboxy group of 4-oxo-1,4-dihydroquinoline-3-carboxylic acid with the amino group of 5-amino-2,4-di-tert-butylphenol. Used for the treatment of cystic fibrosis. It has a role as a CFTR potentiator and an orphan drug. It is a quinolone, a member of phenols, an aromatic amide and a monocarboxylic acid amide.
Ivacaftor (also known as Kalydeco or VX-770) is a drug used for the management of Cystic Fibrosis (CF). It is manufactured and distributed by Vertex Pharmaceuticals. It was approved by the Food and Drug Administration on January 31, 2012, and by Health Canada in late 2012. Ivacaftor is administered as a monotherapy and also administered in combination with other drugs for the management of CF. Cystic Fibrosis is an autosomal recessive disorder caused by one of several different mutations in the gene for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, an ion channel involved in the transport of chloride and sodium ions across cell membranes. CFTR is active in epithelial cells of organs such as of the lungs, pancreas, liver, digestive system, and reproductive tract. Alterations in the CFTR gene result in altered production, misfolding, or function of the protein and consequently abnormal fluid and ion transport across cell membranes. As a result, CF patients produce thick, sticky mucus that clogs the ducts of organs where it is produced making patients more susceptible to complications such as infections, lung damage, pancreatic insufficiency, and malnutrition. Prior to the development of ivacaftor, management of CF primarily involved therapies for the control of infections, nutritional support, clearance of mucus, and management of symptoms rather than improvements in the underlying disease process or lung function (FEV1). Notably, ivacaftor was the first medication approved for the management of the underlying causes of CF (abnormalities in CFTR protein function) rather than control of symptoms.
Ivacaftor is a Cystic Fibrosis Transmembrane Conductance Regulator Potentiator. The mechanism of action of ivacaftor is as a Chloride Channel Activation Potentiator, and Cytochrome P450 2C9 Inhibitor, and P-Glycoprotein Inhibitor, and Cytochrome P450 3A Inhibitor.
See also: Ivacaftor; lumacaftor (component of); Elexacaftor, ivacaftor, tezacaftor; ivacaftor (component of); Ivacaftor; ivacaftor, tezacaftor (component of).

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When used as monotherapy as the product Kalydeco, ivacaftor is indicated for the treatment of cystic fibrosis (CF) in patients aged one month and older who have one mutation in the CFTR gene that is responsive to ivacaftor potentiation based on clinical and/or _in vitro_ assay data. When used in combination with the drug [lumacaftor] as the product Orkambi, ivacaftor is indicated for the management of CF in patients aged one year and older who are homozygous for the _F508del_ mutation in the CFTR gene. If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the _F508del_ mutation on both alleles of the CFTR gene. When used in combination with [tezacaftor] in the product Symdeko, it is used to manage CF in patients 12 years and older who have at least one mutation in the CFTR gene or patients aged 12 or older who are shown to be homozygous for the F508del mutation. When used in combination with tezacaftor and [elexacaftor] in the product Trikafta, it is indicated for the treatment of cystic fibrosis in patients 12 years of age and older who have at least one _F508del_ mutation in the CFTR gene.
Kalydeco tablets are indicated: As monotherapy for the treatment of adults, adolescents, and children aged 6 years and older and weighing 25 kg or more with cystic fibrosis (CF) who have an R117H CFTR mutation or one of the following gating (class III) mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R (see sections 4. 4 and 5. 1). In a combination regimen with tezacaftor/ivacaftor tablets for the treatment of adults, adolescents, and children aged 6 years and older with cystic fibrosis (CF) who are homozygous for the F508del mutation or who are heterozygous for the F508del mutation and have one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272 26A→G, and 3849+10kbC→T. In a combination regimen with ivacaftor/tezacaftor/elexacaftor tablets for the treatment of adults, adolescents, and children aged 6 years and older with cystic fibrosis (CF) who have at least one F508del mutation in the CFTR gene (see section 5. 1). Kalydeco granules are indicated for the treatment of infants aged at least 4 months, toddlers and children weighing 5 kg to less than 25 kg with cystic fibrosis (CF) who have an R117H CFTR mutation or one of the following gating (class III) mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R (see sections 4. 4 and 5. 1). In a combination regimen with ivacaftor/tezacaftor/elexacaftor for the treatment of cystic fibrosis (CF) in paediatric patients aged 2 to less than 6 years who have at least one F508del mutation in the CFTR gene.
Treatment of cystic fibrosis

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A wide variety of CFTR mutations correlate to the Cystic Fibrosis phenotype and are associated with differing levels of disease severity. The most common mutation, affecting approximately 70% of patients with CF worldwide, is known as F508del-CFTR or delta-F508 (ΔF508), in which a deletion in the amino acid phenylalanine at position 508 results in impaired production of the CFTR protein, thereby causing a significant reduction in the amount of ion transporter present on cell membranes. Ivacaftor as monotherapy has failed to show a benefit for patients with delta-F508 mutations, most likely due to an insufficient amount of protein available at the cell membrane for interaction and potentiation by the drug. The next most common mutation, G551D, affecting 4-5% of CF patients worldwide is characterized as a missense mutation, whereby there is sufficient amount of protein at the cell surface, but opening and closing mechanisms of the channel are altered. Ivacaftor is indicated for the management of CF in patients with this second type of mutation, as it binds to and potentiates the channel opening ability of CFTR proteins on the cell membrane. Ivacaftor exerts its effect by acting as a potentiator of the CFTR protein, an ion channel involved in the transport of chloride and sodium ions across cell membranes of the lungs, pancreas, and other organs. Alterations in the CFTR gene result in altered production, misfolding, or function of the protein and consequently abnormal fluid and ion transport across cell membranes. Ivacaftor improves CF symptoms and underlying disease pathology by potentiating the channel open probability (or gating) of CFTR protein in patients with impaired CFTR gating mechanisms. The overall level of ivacaftor-mediated CFTR chloride transport is dependent on the amount of CFTR protein at the cell surface and how responsive a particular mutant CFTR protein is to ivacaftor potentiation.

C₂₄H₃₀N₂O₄

410.51

410.221

1134822-07-3

Ivacaftor;873054-44-5;Ivacaftor-d4;Ivacaftor benzenesulfonate;1134822-09-5;Ivacaftor-d19;1413431-22-7

78357769

Typically exists as solid at room temperature

5.089

91.42

4

5

4

30

671

0

O([H])C1C([H])=C(C(=C([H])C=1C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])N([H])C(C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C2C1=O)=O.O([H])[H]

MYELKYHBCRDZNH-UHFFFAOYSA-N

InChI=1S/C24H28N2O3.H2O/c1-23(2,3)16-11-17(24(4,5)6)20(27)12-19(16)26-22(29)15-13-25-18-10-8-7-9-14(18)21(15)28;/h7-13,27H,1-6H3,(H,25,28)(H,26,29);1H2

N-(2,4-ditert-butyl-5-hydroxyphenyl)-4-oxo-1H-quinoline-3-carboxamide;hydrate

VX770 hydrate; VX 770 hydrate; VX-770; Ivacaftor hydrate; 1134822-07-3; Ivacaftor (hydrate); VX-770 hydrate; N-(2,4-ditert-butyl-5-hydroxyphenyl)-4-oxo-1H-quinoline-3-carboxamide;hydrate; Kalydeco hydrate; SCHEMBL2100895; Ivacaftor hydrate; Trade name: KALYDECO.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

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。

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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 : PEG300 ：Tween 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: 以注射用配方 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 : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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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: 以口服配方 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

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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。

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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。