GABA reuptake

（R） N-[4,4-双（3-甲基-2-噻吩基）丁-3-烯-1-基]尼泊金酸（Tiagabine/NO 328）先前已被证明是小鼠和大鼠的强效抗惊厥药。在这里，我们报告说，NO 328是大鼠前脑突触体制剂（IC50=67 nM）以及神经元和星形胶质细胞原代培养物中γ-[3H]氨基丁酸[（3H]GABA）摄取的强效抑制剂。当NO 328在[3H]GABA摄取之前预孵育时，NO 328对[3H]GABA摄取的抑制显然是混合型的；在没有预孵育的情况下，抑制作用显然是竞争性的。NO 328本身不是GABA摄取载体的底物，但Tiagabine是[3H]GABA摄取的选择性抑制剂。与苯二氮卓受体、组胺H1受体和5-羟色胺1A受体的结合被5-30微M的NO 328抑制，而其他几种受体和摄取位点不受影响。[3H]NO 328在NaCl存在下与大鼠脑膜显示出可饱和和可逆的结合。[3H]NO 328的特异性结合被已知的[3H]GABA摄取抑制剂抑制；然而，GABA和环状氨基酸GABA摄取抑制剂的效力低于预期。这表明结合位点与摄取载体的GABA识别位点不同，而是重叠。[3H]NO 328结合的亲和力常数为18 nM，Bmax为669 pmol/g原始大鼠前脑组织。NaCl依赖性[3H]NO 328结合的区域分布遵循突触体[3H]GABA摄取的区域分布[1]。

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我们在体外研究了Tiagabine对大鼠皮质星形胶质细胞基因组DNA的影响。为了评估DNA损伤，我们使用了一种相对简单的技术，称为单细胞凝胶电泳或彗星测定。Tiagabine溶解于培养液中，分别以1、10、20、50 μg/ml的浓度加入培养12 d的星形胶质细胞。替加滨浓度分别为1和10 μg/ml， 48 h后未见DNA损伤。暴露于20 μg/ml抗癫痫药物的细胞出现中度DNA损伤。50 μg/ml替加滨处理后，DNA断裂更为明显。我们得出结论，在通常推荐的剂量下，替加滨似乎不会对皮质大鼠星形胶质细胞产生负面影响，只有在非常高的浓度下才会诱导DNA断裂。[4]

γ-氨基丁酸（GABA）与包括恐慌在内的焦虑症的病理生理学有关。Tiagabine是一种选择性GABA再摄取抑制剂（SGRI），已被证明可以减轻焦虑症状。这项初步研究评估了噻加宾治疗惊恐障碍患者的疗效和安全性。年龄在18-64岁之间，经DSM-IV诊断为严重至中度惊恐障碍（有或没有广场恐怖症）的男性和女性门诊患者接受了2-20mg/天的开放标签噻加宾治疗，持续10周。结果评估包括Sheehan惊恐障碍量表（SPS）、惊恐障碍严重程度量表（PDSS）、Bandelow恐慌和恐惧症量表（PAS）、汉密尔顿焦虑评定量表（HAM-A）、21分临床医生总体改善量表（CGI-21）、21点患者总体改善（PGI-21）和Sheehan残疾量表（SDS）。在基线时记录得分，此后每周记录一次。在整个研究过程中监测不良事件。在参与该研究的28名患者中，23名患者进行了一次基线后随访，可用于LOCF结果分析。尽管所有结果指标都观察到与基线相比有统计学上的显著降低，但单个量表的百分比改善仅在25-32%的范围内，这在临床上并不显著。Tiagabine通常耐受性良好；最常见的不良反应是恶心、头晕和头痛。只有一名患者因不良事件而停药。这些发现表明，服用噻加宾对惊恐障碍患者可能没有什么好处。[2]

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噻加滨对灰色和白色结构中GABA摄取的影响[3]
为了确定参与白质高亲和力GABA摄取的GABA转运蛋白的类型，我们研究了GABA摄取对Tiagabine的敏感性。Tiagabine是GAT-1 GABA转运蛋白的选择性抑制剂，Ki为∼0.1μM（Thomsen等人，1997），可抑制颞叶皮层和白色结构中的高亲和力GABA摄取（图1B）。在0.1μM时，由颞皮层制成的蛋白脂质体中的高亲和力GABA摄取被抑制了约50%。在白色结构中，0.1μM的噻加宾引起了60-68%的抑制，这明显大于颞叶皮层中的抑制（图1B）。即使在0.33μM的浓度下，与颞叶皮层相比，噻加宾在胼胝体、锥体束和枕叶皮层下的白质中的高亲和力GABA摄取受到的抑制程度略高（图1B）。

以1±2日龄Wistar大鼠为材料制备星形胶质细胞原代培养物，将其去头，并按照Cardile等人的描述获得细胞。星形胶质细胞在含有10%胎牛血清、1 mM l -谷氨酰胺和抗生素的Dulbecco's modi®ed Eagle's培养基/F12培养基中培养，并在湿度为5% CO2/ 95%的环境中于378C培养。在第12天，分别考虑不同的细胞板，作为未处理的对照或Tiagabine处理的星形胶质细胞。为了评估细胞的星形胶质性质，在治疗开始前进行glial®briral酸性蛋白检测。在本研究中，仅考虑了胶质®briral酸性蛋白免疫染色显示90±95%的细胞为星形胶质细胞的培养数据。根据Singh等人的方法使用Comet测定法，很少使用莫迪离子。单层星形胶质细胞（未处理对照和不同Tiagabine处理48 h）用pH 7.4的磷酸盐缓冲盐水（PBS）洗涤两次，用橡胶警棍刮碟悬浮在2ml PBS中，800 g离心15分钟。将球团重新悬浮在小体积PBS中，将细胞的等分物与0.4%台锥蓝溶液混合并计数。剩余的细胞考虑进行彗星试验。显微镜载玻片用100%甲醇清洗，风干，用1% （w/v）标准熔点琼脂糖（NMA）和solidi®ed溶液冲洗。10微升细胞悬液（0.8±1磅105个细胞）与75毫升0.5%低熔点琼脂糖（LMA）混合，并在载玻片上染色。然后加入第三层85 ml LMA。在48℃的低温裂解液（N-laurosil-sarcosine 1%, NaCl 2.5 M, Na2EDTA 10 mM, Triton X-100 1%, DMSO 10%, (pH 10)）中浸泡1小时，在高pH缓冲液（NaOH 300 mM, Na2EDTA 1 mM）中变性20分钟，在25 V的冰浴和半暗条件下在相同的缓冲液中运行25分钟。电泳结束时，载玻片在中和缓冲液（Tris±HCl 0.4 M, (pH 7.5)）中轻轻洗涤三次，用100 ml溴化乙啶（2mg /ml）染色10分钟，并用18磅18毫米的盖玻片覆盖；过量的染料被吸收了。这些载玻片要么立即进行评分，使用与计算机连接的雷茨荧光显微镜。[4]

High-affinity uptake of [3H]GABA into proteoliposomes and fresh homogenates [3]
Plasma membrane transporters for GABA were reconstituted in proteoliposomes according to the method of Danbolt et al. (1990) as described (Trotti et al., 1995, Hassel et al., 2003), starting from 10% homogenates (w/v) in sucrose, 0.32 M. These proteoliposomes have an internal buffer of KCl, 140 mM. Uptake of [3H]GABA, 0.5 μM, final specific activity 5.6 mCi/μmol, was performed in triplicates in the presence of NaCl, 150 mM, and valinomycin, 1 μM, for 15 min at 30 °C; the sequestered radioactivity was trapped on filter paper and quantified by scintillation counting. Blanks were run in duplicates for each structure and were obtained by keeping the samples on ice and adding the sodium ionophore nigericin, 1 μM. Uptake was linear with time for at least 20 min. Previously, uptake by proteoliposomes made from frozen brain tissue has been shown to be the same as for fresh brain homogenates when [3H]glutamate was the transported compound (Hassel et al., 2003), suggesting that freezing does not affect transport activities.
The sensitivity of high-affinity GABA uptake to Tiagabine was investigated in temporal cortex and white structures. Tiagabine, a selective inhibitor of the GAT-1 GABA transporter, with a Ki of 0.1 μM (Thomsen et al., 1997), was added during incubation at 0.1 or 0.33 μM.

Absorption, Distribution and Excretion
Tigaben is almost completely absorbed (>95%). After oral administration, approximately 2% of tigaben is excreted unchanged, with 25% and 63% of the remaining dose excreted in urine and feces, respectively, primarily as metabolites. 109 mL/min [Healthy Subjects] Tigaben is rapidly absorbed, reaching peak plasma concentrations approximately 45 minutes after oral administration on an empty stomach. Tigaben is almost completely absorbed (>95%), with an absolute oral bioavailability of approximately 90%. High-fat meals may decrease the absorption rate of tigaben (mean time to peak is prolonged to 2.5 hours, and mean peak concentration is reduced by approximately 40%), but do not affect its extent of absorption (area under the curve). The pharmacokinetics of tigaben are linear over a single dose range of 2 to 24 mg. Steady state is reached within 2 days after multiple administrations.
Tigaben binds to human plasma proteins in 96% of cases, primarily serum albumin and α1-acid glycoprotein, at concentrations ranging from 10 ng/mL to 10,000 ng/mL. While the relationship between tiagaben plasma concentrations and clinical efficacy is currently unclear, trough concentrations observed at daily doses of 30 to 56 mg ranged from <1 ng/mL to 234 ng/mL in controlled clinical trials.
A diurnal rhythm effect was observed in the pharmacokinetics of tiagaben. The mean steady-state Cmin value was 40% lower in the evening than in the morning. The steady-state AUC value was also 15% lower after evening administration of tiagaben compared to morning administration.
For more complete data on the absorption, distribution, and excretion of tiagabens (9 in total), please visit the HSDB record page.
Metabolism/Metabolites

Tigaben is likely primarily metabolized by the 3A subfamily of hepatocyte pigment P450.
Although the metabolism of tiagabe is not fully elucidated, in vivo and in vitro studies have identified at least two metabolic pathways in humans: 1) epoxidation of thiophene to 5-oxo-tiagabe; 2) glucuronidation. The 5-oxo-tiagabe metabolite does not participate in the pharmacological activity of tiagabe.
Based on in vitro data, tiagabe is likely primarily metabolized by the hepatic cytochrome P450 3A subfamily (CYP 3A), but the possibility that CYP 1A2, CYP 2D6, or CYP 2C19 may also be involved in tiagabe metabolism cannot be ruled out.
Tiagabe is likely primarily metabolized by the hepatic cytochrome P450 3A subfamily.
Elimination pathway: After oral administration of tiagabe, approximately 2% is excreted unchanged, and the remaining 25% and 63% are excreted in urine and feces, respectively, primarily as metabolites.
Half-life: 7-9 hours

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Biological half-life
7-9 hours
……In healthy subjects, the mean elimination half-life of tiagabe is 7 to 9 hours. Compared with patients with hepatic enzyme-induced epilepsy who did not experience it, the elimination half-life in patients with hepatic enzyme-induced epilepsy was shortened by 50% to 65%.
Its half-life is approximately 8 hours, but when used in combination with hepatic enzyme-inducing drugs such as phenobarbital, phenytoin, or carbamazepine, the half-life can be shortened by 2 to 3 hours.

Toxicity Summary
While the exact mechanism of action of tiagabine in humans is unclear, it appears to be a selective GABA reuptake inhibitor. Hepatotoxicity
Limited data exist regarding tiagabine hepatotoxicity. In clinical trials, tiagabine treatment was not associated with elevated serum transaminases or an increased incidence of hepatotoxicity. No case reports of liver injury caused by tiagabine have been published, and its use has not been found to be associated with hypersensitivity syndromes or autoimmune diseases. However, its overall use is limited. Probability Score: E (Unlikely a cause of clinically apparent liver injury). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Infants should be monitored for lethargy, weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using anticonvulsants or psychotropic drugs in combination. Due to very limited experience with tiagabine use during lactation, alternative medications may be preferred, especially in breastfed newborns or preterm infants.
◉ Effects on Breastfed Infants
One mother breastfed her infant while taking tiagabine 24 mg/day, then reduced to 20 mg/day.
Ten newborns aged 4 to 23 days were breastfed while their mothers were taking levetiracetam 1000 to 3000 mg daily, with no adverse reactions reported. One mother was concurrently taking tiagabine 30 mg/day, clobazian 45 mg/day, and oxcarbazepine 600 mg/day.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

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Protein Binding
96%Interaction
/Concomitant use of tiagabine with alcohol or central nervous system depressants may exacerbate central nervous system depression.
In patients taking carbamazepine, phenobarbital, phenytoin, or primidone, tiagabine clearance is increased by 60%.
Tigaben causes a slight decrease (approximately 10%) in the steady-state concentration of valproic acid; in vitro studies have shown that valproic acid can reduce the protein binding rate of tiagaben from 96.3% to 94.8%, resulting in an increase in the concentration of free tiagaben by approximately 40%; the clinical significance of this finding is unclear.
Concomitant use of cimetidine (800 mg/day) in patients taking tiagaben long-term has no effect on the pharmacokinetics of tiagaben.
For more complete data on drug interactions of tiagaben (13 items in total), please visit the HSDB record page.

[1]. (R)-N-[4,4-bis(3-methyl-2-thienyl)but-3-en-1-yl]nipecotic acid binds with high affinity to the brain gamma-aminobutyric acid uptake carrier. J Neurochem. 1990 Feb;54(2):639-47.
[2]. An open-label study of tiagabine in panic disorder. Psychopharmacol Bull, 2007. 40(3): p. 32-40.
[3]. High-affinity GABA uptake and GABA-metabolizing enzymes in pig forebrain white matter: a quantitative study. Neurochem Int, 2007. 50(2): p. 365-70.
[4]. Tiagabine treatment and DNA damage in rat astrocytes: an in vitro study by comet assay. Neurosci Lett. 2001 Jun 22;306(1-2):17-20.

Tiagabine is a piperidine monocarboxylic acid, a derivative of (R)-nipoic acid, in which the hydrogen atom on the nitrogen atom is replaced by 1,1-bis(3-methyl-2-thienyl)but-1-en-4-yl. It is a GABA reuptake inhibitor, usually used in the form of hydrochloride to treat epilepsy. It is both a GABA reuptake inhibitor and an anticonvulsant. Tiagabine is a piperidine monocarboxylic acid, β-amino acid, thiophene compound, and tertiary amine compound. It is functionally related to (R)-nipoic acid. It is the conjugate base of tiagabine (1+). Tiagabine is an anticonvulsant. It is also used to treat panic disorder, like some other anticonvulsants. Although the exact mechanism by which tiagabine works in the human body is not fully understood, it appears to be a selective GABA reuptake inhibitor. Tiagabine is an antiepileptic drug. The physiological effect of tiagabine is achieved by reducing disordered electrical activity in the central nervous system. Tiagabine is a unique anticonvulsant primarily used as adjunctive therapy in the treatment of partial seizures in adults or children. Tiragbin treatment does not cause elevated serum transaminases, and there are no reports of clinically significant liver damage caused by tiragbin; even if it occurs, it is certainly very rare. Tiragbin is an anticonvulsant. Like some other anticonvulsants, it is used to treat panic disorders. Although the exact mechanism of action of tiragbin in the human body is unclear, it appears to be a selective GABA reuptake inhibitor. Tiragbin is a nipoise derivative that acts as both a GABA reuptake inhibitor and an anticonvulsant. It is used to treat epilepsy, particularly refractory partial seizures. See also: tiragbin hydrochloride (in salt form). Tiragbin hydrochloride monohydrate (its active ingredient).

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Drug Indications
For the treatment of partial seizures
FDA Label

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Mechanism of Action
Although the exact mechanism of action of tiragbin in the human body is unclear, it appears to be a selective GABA reuptake inhibitor. Although the exact mechanism of action of tiagabe is not fully understood, this drug enhances GABA-mediated inhibitory neurotransmission. Tiagabe increases GABA levels in the extracellular spaces of the globus pallidus, ventral globus pallidus, and substantia nigra, suggesting a GABA-mediated anticonvulsant mechanism (i.e., inhibition of nerve impulse transmission leading to seizures). Tiagabe inhibits the reuptake of GABA by presynaptic neurons and glial cells and increases the amount of GABA available for postsynaptic receptor binding. The drug does not stimulate GABA release and, at concentrations inhibiting GABA uptake, is inactive at other receptor binding and uptake sites. Tiagabe selectively blocks presynaptic GABA uptake by reversibly and saturatingly binding to recognition sites associated with GABA transporters on neuronal and glial cell membranes. In vitro binding studies have shown that thiagaben has no significant inhibitory effect on the uptake of dopamine, norepinephrine, serotonin, glutamate, or choline, and its binding to dopamine D1 or D2 receptors, cholinergic muscarinic receptors, and serotonergic type 1A, 2, or 3 receptors (5HT1A, 5HT2, or 5HT3, respectively) is also insignificant. It also binds to α1- or α2-adrenergic receptors; β1- or β2-adrenergic receptors; histamine H2 or H3 receptors; adenosine A1 or A2 receptors; opioid μ or κ1 receptors; glutamate N-methyl-D-aspartate (NMDA) receptors; or GABAA receptors. Furthermore, thiagaben has very low or no affinity for sodium or calcium channels. Thiagabe binds to histamine H1 receptors, 5-HT1B receptors, benzodiazepine receptors, and chloride channel receptors at concentrations 20-400 times higher than those inhibiting GABA uptake.

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Therapeutic Use
Thiagabe is indicated as adjunctive therapy to other antiepileptic drugs for the treatment of partial seizures in adults and children aged 12 years and older. /US Product Label Content/

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Drug Warnings
While thiagbene can reduce the frequency of seizures in patients with epilepsy, its use has been associated with ambivalent seizures in patients without a history of epilepsy.
Post-marketing reports have shown that thiagbene use has been associated with new-onset epilepsy and status epilepticus in patients without a history of epilepsy. Dosage may be a significant triggering factor for seizures, although seizures have been reported in patients taking as little as 4 mg of thiagbene daily. In most cases, patients are taking other medications (antidepressants, antipsychotics, stimulants, anesthetics) that are thought to lower the seizure threshold. Some seizures occur before or after dose increases, even when the previous dose was stable. The current label dosage recommendations for tiagabine in treating epilepsy are based on use in patients aged 12 years and older with partial seizures, most of whom are taking enzyme-inducible antiepileptic drugs (AEDs; such as carbamazepine, phenytoin sodium, primidone, and phenobarbital), which reduce tiagabine's plasma concentration by inducing its metabolism. When tiagabine is used alone without combination with an AED, plasma concentrations are approximately twice those observed in studies on which the current dosage recommendations are based. The safety and efficacy of tiagabine have not been established, and its indication is limited to adjunctive therapy for partial seizures in adults and children aged 12 years and older. For more complete data on drug warnings for tiagabine (19 in total), please visit the HSDB record page.

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Pharmacodynamics
Tiagabine is primarily used as an anticonvulsant for adjunctive treatment of epilepsy. The exact mechanism by which tiagabe exerts its antiepileptic effect is unclear, but it is believed to be related to its ability to enhance the activity of γ-aminobutyric acid (GABA, the main inhibitory neurotransmitter in the central nervous system). Tiagabe binds to recognition sites associated with GABA uptake carriers. It is speculated that tiagabe blocks the uptake of GABA by presynaptic neurons through this action, thereby making more GABA available to bind to receptors on the postsynaptic cell surface. Based on our current and previous findings, we can conclude that tiagabe does not appear to have a negative effect on rat cortical astrocytes at commonly recommended doses, and only induces DNA fragmentation at very high concentrations. However, since astrocytes are more resistant to oxidative stress than neurons, the possibility that tiagabe may also induce neuronal DNA fragmentation at lower concentrations cannot be ruled out. [4]

C20H28CLNO3S2

430.024222373962

429.119

145821-57-4

Tiagabine hydrochloride;145821-59-6;Tiagabine;115103-54-3

67065562

Typically exists as solid at room temperature

98

3

6

6

27

474

1

CC1=C(SC=C1)C(=CCCN2CCC[C@H](C2)C(=O)O)C3=C(C=CS3)C.O.Cl

KOZCGZMZXXVHCF-GGMCWBHBSA-N

InChI=1S/C20H25NO2S2.ClH.H2O/c1-14-7-11-24-18(14)17(19-15(2)8-12-25-19)6-4-10-21-9-3-5-16(13-21)20(22)23;;/h6-8,11-12,16H,3-5,9-10,13H2,1-2H3,(H,22,23);1H;1H2/t16-;;/m1../s1

(3R)-1-[4,4-bis(3-methylthiophen-2-yl)but-3-enyl]piperidine-3-carboxylic acid;hydrate;hydrochloride

NO050328 hydrochloride hydrate; NNC-05-0328; NNC-050328; NO 329; NO-05-0328; NO329; trade name Gabitril

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)

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

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。