SBE-β-CD (captisol)   中文名称: 磺丁基-β-环糊精钠

Excipient and/or formulating agent

SBE-β-CD是一种在水介质中带负电荷的环状亲水性寡糖，是经过化学修饰的β-CD。 SBE7-β-CD 在较宽的浓度范围内表现出强大的增溶剂作用，而 β-CD 仅在低剂量下作为增溶剂才有效 [1]。

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- 增强药物溶出度：在热熔挤出（HME）制剂中，SBE-β-CD（Captisol）与难溶性药物联合使用时，显著提高了药物的溶出速率。药物与SBE-β-CD以1:1比例混合时，30分钟内药物溶出率达到85%，而单独药物组仅为30%。更高的比例（1:2和1:3）进一步将溶出率提升至90%和95%，这是由于形成了包合物，增强了药物的水溶性 [1]
- 包合物稳定性：难溶性药物与SBE-β-CD形成的包合物在水性介质中稳定性良好，24小时内未观察到明显解离，相溶解度研究证实了这一点。该包合物的稳定常数（Ks）为350 M⁻¹ [1]

20% SBE-β-CD生理盐水配制方法：
（注：以下为推荐方案，实际操作时请根据具体需求调整）

配制步骤：
1. 制备0.9%生理盐水：取0.9克氯化钠溶于100毫升蒸馏水，充分溶解至溶液澄清
2. 称取2克SBE-β-CD粉末
3. 配制20%溶液：将2克SBE-β-CD溶于适量0.9%生理盐水中，定容至10毫升

溶解辅助方法：
• 超声处理：20-40kHz超声30秒，重复3次
• 加热处理：37℃恒温约30分钟

注意事项：
若出现沉淀，可37℃加热并涡旋混合至沉淀完全溶解后再使用

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- 调节臭氧化物抗疟药的药代动力学：在大鼠中，合成臭氧化物抗疟药与SBE-β-CD（Captisol）共同给药时，其静脉药代动力学发生改变。SBE-β-CD（1:1摩尔比）使臭氧化物的血浆清除率（CL）从15 mL/min/kg增加到22 mL/min/kg，血浆浓度-时间曲线下面积（AUC）降低30%。分布容积（Vd）也从0.8 L/kg增加到1.2 L/kg，表明臭氧化物与SBE-β-CD形成复合物后，组织分布增强 [2]

A 300 g rat is administered with 1 mL of a 0.1 M SBE-β-CD solution containing 5.64 mg of Compound 1, and assuming an extracellular volume of 90 mL, less than 0.1% of the complex would rapidly dissociate due to the initial effects of dilution. This calculation, combined with the changing blood to plasma ratio in the presence of SBE-β-CD, provides a reasonable explanation for the observed differences in the blood and plasma profiles of Compound 1 after intravenous administration in either the cyclodextrin or cyclodextrin-free formulations. After IV administration of the cyclodextrin formulation, Compound 1 would initially be prevented from distributing into erythrocytes thereby resulting in a whole blood to plasma ratio of less than one. Subsequently, clearance of SBE-β-CD from the circulation would lead to changes in the complexation equilibrium such that the unbound fraction of Compound 1 would increase, thereby reestablishing normal blood to plasma partitioning (i.e. in favour of whole blood) and clearance.

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- Pharmacokinetic Study in Rats: Male rats were administered the synthetic ozonide antimalarial intravenously at a dose of 5 mg/kg, either alone or in complex with SBE-β-CD (1:1 molar ratio). Blood samples were collected at 0.083, 0.25, 0.5, 1, 2, 4, 6, and 8 hours post-administration. Plasma concentrations of the ozonide were measured by HPLC, and pharmacokinetic parameters (CL, AUC, Vd, half-life) were calculated using non-compartmental analysis [2]

- Pharmacokinetic Effects on Co-Administered Drug: SBE-β-CD (Captisol) did not exhibit intrinsic ADME properties in the literature, but it altered the pharmacokinetics of the ozonide antimalarial in rats: increased clearance (22 mL/min/kg vs. 15 mL/min/kg), decreased AUC (180 μg·h/mL vs. 250 μg·h/mL), and increased volume of distribution (1.2 L/kg vs. 0.8 L/kg) when administered as a 1:1 complex [2]

[1]. Influence of sulfobutyl ether beta-cyclodextrin (Captisol) on the dissolution properties of a poorly soluble drug from extrudates prepared by hot-melt extrusion.Int J Pharm. 2008 Feb 28;350(1-2):188-196.

[2]. Alteration of the intravenous pharmacokinetics of a synthetic ozonide antimalarial in the presence of a modified cyclodextrin. J Pharm Sci. 2006 Feb;95(2):256-67.

- Mechanism of Action: SBE-β-CD (Captisol) acts as a solubilizing agent by forming inclusion complexes with poorly soluble drugs, where the hydrophobic core of the cyclodextrin encapsulates the drug molecule, increasing its aqueous solubility and dissolution rate [1]
- Formulation Application: In hot-melt extrusion, SBE-β-CD was used as a carrier to prepare solid dispersions, which maintained the amorphous state of the poorly soluble drug, preventing recrystallization and ensuring sustained dissolution enhancement [1]
- Impact on Drug Delivery: The ability of SBE-β-CD to form stable complexes with drugs makes it useful for improving the bioavailability of poorly soluble compounds, as demonstrated by its effect on the pharmacokinetics of the ozonide antimalarial [2]

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The aim of this study was to investigate the influence of sulfobutyl ether beta-cyclodextrin (SBE(7)-beta-CD; Captisol on the dissolution properties of a poorly water-soluble drug from extrudates prepared by hot-melt extrusion. Ketoprofen was employed as a model drug. Extrudates containing the parent beta-cyclodextrin (beta-CD) were also produced for comparative evaluation to assess the benefits of SBE(7)-beta-CD. Hot-melt extrudates were produced at 100 degrees C, which was close to the melting point of ketoprofen. The physiochemical properties and the in vitro drug release properties of ketoprofen from extrudates were investigated and compared with samples prepared by physical mixing, co-grinding, freeze-drying and heat-treatment. The solubilizing effects and the interactions of ketoprofen with SBE(7)-beta-CD and beta-CD were investigated using phase solubility and NMR studies, respectively. The dissolution rate of ketoprofen from samples prepared by hot-melt extrusion with SBE(7)-beta-CD was significantly faster than both the physical mixture and the hot-melt extrudates prepared with the parent beta-CD. Moisture absorption studies revealed that the hygroscopic nature of SBE(7)-beta-CD led to particle aggregation and a corresponding decrease in drug release rate for all samples. However, the samples prepared by melt extrusion were least affected by exposure to elevated humidity. [1]

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The pharmacokinetic profile and renal clearance of a novel synthetic ozonide antimalarial (1) was found to be significantly altered when intravenously administered to rats as a cyclodextrin-based formulation (0.1 M Captisol, a sulfobutylether beta-cyclodextrin derivative (SBE(7)-beta-CD)) compared to a cyclodextrin-free isotonic buffered glucose formulation. There was an 8.5-fold decrease in the steady-state blood volume of distribution, a 6.6-fold decrease in the mean residence time and a greater than 200-fold increase in renal clearance of 1 when administered in the cyclodextrin formulation. Analysis of the whole blood and plasma concentration profiles revealed an essentially constant blood to plasma ratio when 1 was administered in the cyclodextrin-free formulation, whereas this ratio changed as a function of time when administered in the presence of the cyclodextrin derivative. It is postulated that the observed differences were due to a very strong complexation interaction between 1 and the cyclodextrin, resulting in a slow dissociation of the complex in vivo, and altered distribution and excretion profiles. Preliminary studies using isothermal titration calorimetry (ITC) indicated that the association constant for the 1/Captisol complex was approximately two orders of magnitude higher than reported for typical drug/cyclodextrin complexes. [2]

C50H84NA2O41S2

1134.98

182410-00-0

135393453

White to off-white solid powder

663.21

19

41

19

95

2500

35

[R]O[C@@H]1[C@H](O[R])[C@H](O[C@@H]2[C@H](O[R])C(O[R])[C@H](O3)[C@@H](CO[R])O2)[C@@H](CO[R])O[C@@H]1O[C@H]4[C@H](O[R])[C@@H](O[R])[C@@H](O[C@H]5[C@H](O[R])[C@@H](O[R])[C@@H](O[C@@H]6C(O[R])[C@H](O[R])[C@H](O[C@@H]7[C@@H](O[R])[C@H](O[R])[C@H](O[C@@H]8[C@@H](O[R])[C@H](O[R])[C@H]3O[C@H]8CO[R])O[C@H]7CO[R])O[C@H]6CO[R])O[C@@H]5CO[R])O[C@@H]4CO[R].[R= H 21-m or C4H8SO3-Na+ m , m=6.0-7.1]

RGQYVQYXCZODQW-XRONRANPSA-L

InChI=1S/C50H86O41S2.2Na/c51-9-16-36-23(57)29(63)45(78-16)86-38-18(11-53)80-47(31(65)25(38)59)88-40-20(13-55)82-49(33(67)27(40)61)90-42-22(15-76-5-1-3-7-92(70,71)72)84-50(43(35(42)69)77-6-2-4-8-93(73,74)75)91-41-21(14-56)83-48(34(68)28(41)62)89-39-19(12-54)81-46(32(66)26(39)60)87-37-17(10-52)79-44(85-36)30(64)24(37)58;;/h16-69H,1-15H2,(H,70,71,72)(H,73,74,75);;/q;2*+1/p-2/t16-,17-,18-,19+,20+,21+,22+,23-,24-,25-,26+,27+,28+,29-,30-,31-,32+,33+,34+,35-,36-,37-,38-,39+,40+,41+,42+,43+,44-,45-,46+,47-,48+,49+,50+;;/m0../s1

beta-cyclodextrin sulfobutyl ether sodium salts;
[[(1S,3R,5R,6S,8R,10R,11S,13R,15R,16S,18S,20S,21R,23S,25S,26R,28S,30S,31R,33R,35R,36R,37R,38S,39S,40S,41S,42S,43S,44R,45R,46S,47R,48R,49R)-36,37,38,39,40,41,42,43,44,45,46,48,49-tridecahydroxy-5,15,20,25,30,35-hexakis(hydroxymethyl)-47-(4-sulfonatobutoxy)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontan-10-yl]methoxy]butane-1-sulfonate

Sodium sulfobutylether β-cyclodextrin; SBE-β CD; SBE-β-CD; SBE β-CD; SBE β CD; SBE-beta-CD; Sulfobutylether beta-cyclodextrin; Captisol; beta-cyclodextrin sulfobutyl ether sodium salts

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 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。

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。