Tiotropium Bromide hydrate (BA-679 BR)   中文名称: 噻托溴铵

体外活性：噻托溴铵是一种有效的毒蕈碱拮抗剂，对 M1、M2 和 M3 受体具有相同的亲和力，其效力比异丙托溴铵强约 10 倍。噻托溴铵对胆碱能神经引起的豚鼠和人呼吸道收缩具有有效的抑制作用，其起效比阿托品或异丙托溴铵慢。噻托溴铵、异丙托溴铵和阿托品都会增加神经刺激时乙酰胆碱的释放，并且对于三种拮抗剂来说，这种作用同样会很快消失。噻托溴铵与 M3 受体（气道平滑肌上）缓慢解离，但与 M2 自身受体（胆碱能神经末梢）快速解离。 Tiotropium 显着抑制 AM、MonoMac6 和 A549 细胞释放趋化物质。噻托溴铵抑制 PBMC 产生 Th2 细胞因子。激酶测定：噻托溴铵水合物是一种抗胆碱能药和支气管扩张药以及毒蕈碱受体拮抗剂。目标：mAChR 噻托溴铵 (Ba 679 BR) 是一种新型强效且持久的毒蕈碱拮抗剂，已开发用于治疗慢性阻塞性气道疾病 (COPD)。 [3H]噻托溴铵在人肺中的结合研究证实，这是一种有效的毒蕈碱拮抗剂，对 M1、M2 和 M3 受体具有相同的亲和力，并且比异丙托溴铵的效力大约高 10 倍。体外噻托溴铵对胆碱能神经引起的豚鼠和人气道收缩具有有效的抑制作用，其起效比阿托品或异丙托溴铵慢。噻托溴铵与 M3 受体（气道平滑肌上）缓慢解离，但与 M2 自身受体（胆碱能神经末梢）快速解离。噻托溴铵是一种季铵衍生物，可与毒蕈碱受体结合。然而，尽管噻托溴铵以高亲和力与 M1、M2 和 M3 亚型毒蕈碱受体结合，但它与 M1 和 M3 受体的解离速度非常慢，但与 M2 受体的解离速度更快，从而赋予其独特的动力学选择性。

在急性和慢性哮喘小鼠模型中，Tiotropium bromide 显着减少气道炎症和支气管肺泡灌洗液 (BALF) 中 Th2 细胞因子的产生。噻托溴铵显着降低哮喘小鼠模型中的杯状细胞化生、气道平滑肌厚度和气道纤维化。在慢性模型中，噻托溴铵可降低 BALF 中 TGF-β1 的水平。噻托溴铵可抑制持续性过敏性哮喘豚鼠模型中气道平滑肌质量、肌球蛋白表达和收缩力的增加。在慢性阻塞性肺疾病 (COPD) 豚鼠模型中，噻托溴铵可消除 LPS 诱导的中性粒细胞、杯状细胞、胶原蛋白沉积和肌肉化微血管的增加，但对肺气肿没有影响。

Respir Med.2007 Nov;101(11):2386-94;Clin Exp Allergy.2010 Aug;40(8):1266-75.

C19H22NO4S2.BR.XH2O

490.43

139404-48-1

136310-93-5 [Tiotropium Bromide (BA679 BR)]

C[N+]1([C@@H]2CC(C[C@H]1[C@H]3[C@@H]2O3)OC(=O)C(C4=CC=CS4)(C5=CC=CS5)O)C.[Br-]

DQHNAVOVODVIMG-RGECMCKFSA-M

InChI=1S/C19H22NO4S2.BrH/c1-20(2)12-9-11(10-13(20)17-16(12)24-17)23-18(21)19(22,14-5-3-7-25-14)15-6-4-8-26-15;/h3-8,11-13,16-17,22H,9-10H2,1-2H3;1H/q+1;/p-1/t11?,12-,13+,16-,17+;

(1R,2R,4S,5S,7s)-7-(2-hydroxy-2,2-di(thiophen-2-yl)acetoxy)-9,9-dimethyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-9-ium bromide

BA 679BR; PUR-0200; BA 679BR; BA-679BR; BA679BR; PUR0200; PUR 0200; Tiotropium bromide, trade name: Spiriva.

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)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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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。