Hex(?1-4)[Hex(?1-6)]Hex(?1-4)Hex | 119400-89-4

• 物质功能分类: 生物化工 - 糖类化合物 - 多糖
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Hex(?1-4)[Hex(?1-6)]Hex(?1-4)Hex
• 英文别名: 2-[[4,5-dihydroxy-3-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-2-yl]methoxy]-6-(hydroxymethyl)oxane-3,4,5-triol
• CAS: 119400-89-4；9005-79-2；337376-15-5
• 化学式: C₂₄H₄₂O₂₁
• 分子量: 666.6
• InChiKey: BYSGBSNPRWKUQH-UHFFFAOYSA-N

物化性质

• 熔点：
  270-280 °C (dec.)
• 比旋光度：
  D25 +196 to +197°
• 密度：
  1.629 g/cm3(Temp: -5 °C)
• 溶解度：
  H2O：20 mg/mL，清澈至浑浊，淡黄色
• LogP：
  -5.590 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  -8.5
• 重原子数：
  45
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  348
• 氢给体数：
  14
• 氢受体数：
  21

ADMET

代谢

艾考葡萄糖是经过α-淀粉酶代谢成低度聚合的寡糖，包括麦芽糖、麦芽三糖、麦芽四糖以及更高分子量的物种。

Icodextrin is metabolized by alpha-amylase into oligosaccharides with a lower degree of polymerization), including maltose, maltotriose, maltotetraose, and higher molecular weight species.

来源:DrugBank

代谢

艾考葡萄糖苷被α-淀粉酶代谢成聚合度较低的寡糖，包括麦芽糖（DP2）、麦芽三糖（DP3）、麦芽四糖（DP4）以及更高分子量的物种。在一项单次剂量研究中，DP2、DP3和DP4在血浆中的浓度逐渐上升，其曲线与总艾考葡萄糖苷相似，在留置结束时达到峰值，之后下降。

Icodextrin is metabolized by alpha-amylase into oligosaccharides with a lower degree of polymerization (DP), including maltose (DP2), maltotriose (DP3), maltotetraose (DP4), and higher molecular weight species. In a single dose study, DP2, DP3 and DP4 showed a progressive rise in plasma concentrations with a profile similar to that for total icodextrin, with peak values reached by the end of the dwell and declining thereafter.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在植入腹膜导管的雄性Wistar大鼠中，每天两次连续3周灌注20毫升7.5%的基于艾考淀粉的腹膜透析液（IPDF；ICO组，n=12）或3.86%的基于葡萄糖的腹膜透析液（GLU组，n=11）。在第10天（D1）和第21天（D2）的ICO和GLU组中，使用30毫升IPDF进行了4小时的留腹研究。使用放射性标记血清白蛋白（RISA）作为大分子体积标记物。透析液样本在3、15、30、60、90、120和240分钟时收集。血液样本在留腹开始前和结束时抽取。在所有留腹研究中，由于高分子量（MW）组分减少，透析液中总艾考淀粉浓度降低，而艾考淀粉低MW代谢物显著增加。α-淀粉酶活性在透析液中增加，在血浆中减少。在大约4小时的留腹期间，约有60%的艾考淀粉从腹腔中被吸收。低MW艾考淀粉代谢物在透析液中已经出现在3分钟时，麦芽糖（G2）、麦芽三糖（G3）、麦芽四糖（G4）和麦芽五糖（G5）逐渐增加，在60分钟时达到最大浓度。麦芽六糖（G6）和麦芽七糖（G7）在3分钟时就已经被检测到，但在留腹期间没有显著变化。在两次4小时留腹研究（D1和D2）期间，ICO组和GLU组透析液中的总艾考淀粉和艾考淀粉代谢物浓度以及α-淀粉酶活性在D1或D2期间没有差异。在留腹结束时，血浆中没有检测到艾考淀粉代谢物。在两次4小时留腹期间，ICO和GLU组透析液中的α-淀粉酶活性增加了六到八倍，而血浆中的α-淀粉酶活性下降了21%-26%；在D1或D2期间，ICO和GLU组之间没有显著差异。透析液中的α-淀粉酶活性与艾考淀粉从腹腔消失的速率以及透析液中G2、G3、G6和G7的浓度强烈相关。透析液中高分子量组分浓度的下降和艾考淀粉低分子量代谢物的增加表明，腹膜内的α-淀粉酶介导了艾考淀粉的代谢，以及主要是较小艾考淀粉代谢物从透析液中的运输。然而，在这些非尿毒症大鼠的血浆中没有检测到艾考淀粉，这表明它被代谢并通过肾脏排泄了。...

Male Wistar rats with implanted peritoneal catheters were infused twice daily for 3 weeks with 20 mL 7.5% icodextrin-based peritoneal dialysis fluid (IPDF; ICO group, n = 12) or 3.86% glucose-based peritoneal dialysis fluid (GLU group, n = 11). A 4-hour dwell study using 30 mL IPDF was performed on day 10 (D1) and day 21 (D2) in both the ICO and the GLU groups. Radiolabeled serum albumin (RISA) was used as a macromolecular volume marker. Dialysate samples were collected at 3, 15, 30, 60, 90, 120, and 240 minutes. Blood samples were drawn before the start and at the end of the dwell. During all dwell studies, the dialysate concentrations of total icodextrin decreased due to decrease in high molecular weight (MW) fractions, whereas there was a marked increase in icodextrin low MW metabolites. alpha-Amylase activity increased in dialysate and decreased in plasma. About 60% of the total icodextrin was absorbed from the peritoneal cavity during the 4-hour dwells. Low MW icodextrin metabolites were present in the dialysate already at 3 minutes, and maltose (G2), maltotriose (G3), maltotetraose (G4), and maltopentaose (G5) increased progressively, reaching maximum concentrations at 60 minutes. Maltohexaose (G6) and maltoheptaose (G7) were also detected already at 3 minutes but did not change significantly during the dwells. During the two 4-hour dwell studies (D1 and D2), the concentrations of total icodextrin and icodextrin metabolites and alpha-amylase activity in dialysate did not differ between the ICO and GLU groups, during either D1 or D2. No icodextrin metabolites were detected in plasma at the end of the dwells. alpha-Amylase activity in the dialysate increased six- to eightfold whereas plasma alpha-amylase activity decreased by 21% - 26% during the two 4-hour dwells in both the ICO and the GLU groups; there were no significant differences between the ICO and the GLU groups during either D1 or D2. alpha-Amylase activity in the dialysate correlated strongly with the disappearance rate of icodextrin from the peritoneal cavity during the 4-hour dwells, and with the concentrations of G2, G3, G6, and G7 in dialysate. The decline in the dialysate concentrations of high MW fractions and the increase in low MW metabolites of icodextrin suggest intraperitoneal alpha-amylase mediated the metabolism of icodextrin and the transport of predominantly the smaller icodextrin metabolites from dialysate. However, no icodextrin could be detected in plasma, suggesting that it was metabolized and excreted by the kidney in these nonuremic rats. ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下），以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，协助通气。通过非重复呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预期癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污染后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

人类暴露研究... 本研究的目的是检查接受标准葡萄糖和含艾考淀粉的溶液进行连续非卧床腹膜透析（CAPD）患者的胰岛素抵抗。我们中心的所有非糖尿病CAPD患者都被研究了：总共44名患者，平均CAPD治疗时间为36.2 ± 23.7个月。其中27名（11名男性和16名女性）平均年龄为46 ± 16岁，接受标准葡萄糖溶液治疗（葡萄糖组）。另外17名患者（10名男性和7名女性）平均年龄为49 ± 16岁，白天接受标准葡萄糖溶液治疗，晚上使用艾考淀粉滞留，中位时间为12 ± 6.3个月（艾考淀粉组）。葡萄糖组的早晨空腹血清胰岛素水平为20.59 ± 17.86，艾考淀粉组为10.15 ± 6.87（p = 0.0001）。葡萄糖组的稳态模型评估方法（HOMA）得分显著高于艾考淀粉组（4.8 ± 4.1 对 2.3 ± 1.7；p = 0.025）。在HOMA（IR+）患者中，发现HOMA评分与胰岛素、空腹血浆葡萄糖和甘油三酯水平有显著正相关。艾考淀粉组中有20名患者（74%）和葡萄糖组中有15名患者（88%）患有高血压，但两组之间没有统计学上的显著差异（p = 0.13）。两组在体重指数和血清葡萄糖、总胆固醇、LDL胆固醇、VLDL胆固醇、HDL胆固醇、甘油三酯、完整的甲状旁腺激素（iPTH）和纤维蛋白原水平方面没有显著差异。总之，长期夜间滞留使用艾考淀粉可以减少CAPD患者的血清胰岛素水平并增加胰岛素敏感性。

/HUMAN EXPOSURE STUDIES/ ... The purpose of this study was to examine the insulin resistance in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with standard glucose and icodextrin containing solutions. The entire non diabetic CAPD patients of our center were studied: forty-four patients in all who were on CAPD treatment for 36.2 +/- 23.7 months. Twenty-seven of them (11 male and 16 female) with a mean age of 46 +/- 16 years were treated with standard glucose solutions (glucose group). The other 17 patients (10 male and 7 female) with a mean age of 49 +/- 16 years were treated with standard glucose solutions during the day and icodextrin dwell during the night, for a median of 12 +/- 6.3 months (icodextrin group). Morning fasting serum insulin levels were 20.59 +/- 17.86 in the glucose group and 10.15 +/- 6.87 in the icodextrin group (p = 0.0001). Homeostasis Model Assessment Method scores of the glucose group were significantly higher (4.8+/-4.1 vs 2.3+/- 1.7; p = 0.025) than the icodextrin group. A significant positive correlation of HOMA score with insulin, fasting plasma glucose, and triglyceride levels were found in HOMA (IR+) patients. Twenty patients of the icodextrin group (74%) and 15 patients of the glucose group (88%) were hypertensive, but there was no statistically significant difference between the two groups (p = 0.13). The groups showed no significant differences for body mass index and serum levels of glucose, total cholesterol, LDL cholesterol, VLDL cholesterol, HDL cholesterol, triglyceride, intact parathyroid hormone (iPTH), and fibrinogen. In conclusion, the use of icodextrin in the long nighttime dwell can reduce serum insulin levels and increase insulin sensitivity in CAPD patients.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

EXTRANEAL的过量经验数据尚不可用。预期EXTRANEAL过量会导致血清中异麦芽糖和代谢物水平升高，但尚不清楚超出临床试验中使用的暴露量可能会导致哪些体征或症状。如果发生EXTRANEAL过量，应继续提供基于葡萄糖的腹膜透析液进行腹膜透析。

/SIGNS AND SYMPTOMS/ No data are available on experiences of overdosage with EXTRANEAL. Overdosage of EXTRANEAL would be expected to result in higher levels of serum icodextrin and metabolites, but it is not known what signs or symptoms might be caused by exposure in excess of the exposures used in clinical trials. In the event of overdosage with EXTRANEAL, continued peritoneal dialysis with glucose-based solutions should be provided.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

在12小时的停留期间，注入的艾考淀粉糖有40%从腹膜溶液中被吸收。

40% of instilled icodextrin was absorbed from the peritoneal solution during a 12-hour dwell.

来源:DrugBank

吸收、分配和排泄

从腹膜腔吸收艾考糖肽遵循零级动力学，与通过腹膜淋巴途径的对流传输一致。在一项使用艾考糖肽（EXTRANEAL）的单剂量药代动力学研究中，在12小时的停留期间，从腹膜溶液中吸收了大约40%（60克）的注入艾考糖肽。艾考糖肽的血浆水平在停留期间上升，在引流后下降。艾考糖肽及其代谢物（中位Cpeak 2.2克/升）的血浆峰值水平在长时间停留交换结束时观察到（中位Tmax = 13小时）。

Absorption of icodextrin from the peritoneal cavity follows zero-order kinetics consistent with convective transport via peritoneal lymphatic pathways. In a single-dose pharmacokinetic study using EXTRANEAL (icodextrin), a median of 40% (60 g) of the instilled icodextrin was absorbed from the peritoneal solution during a 12-hour dwell. Plasma levels of icodextrin rose during the dwell and declined after the dwell was drained. Peak plasma levels of icodextrin plus its metabolites (median Cpeak 2.2g/L) were observed at the end of the long dwell exchange (median Tmax = 13 hours).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在稳态下，icodeextrin及其代谢物的平均血浆水平约为5克/升。在多次给药研究中，icodeextrin的稳态水平在一周内达到。在停止icodeextrin给药后，大约两周内，icodeextrin及其代谢物的血浆水平恢复到基线值。

At steady-state, the mean plasma level of icodextrin plus its metabolites was about 5 g/L. In multidose studies, steady-state levels of icodextrin were achieved within one week. Plasma levels of icodextrin and metabolites return to baseline values within approximately two weeks following cessation of icodextrin administration.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

稳态血浆中碘克酸代谢物的水平在一周内达到，并且在长期给药期间观察到稳定的血浆水平。

Steady-state plasma levels of icodextrin metabolites were achieved within one week and stable plasma levels were observed during long-term administration.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

艾考昔亭通过肾脏排泄，与残余肾功能水平成正比。艾考昔亭的小分子代谢物也可能在艾考昔亭全身吸收和代谢后，从血浆扩散到腹膜腔。

Icodextrin undergoes renal elimination in direct proportion to the level of residual renal function. Diffusion of the smaller icodextrin metabolites from plasma into the peritoneal cavity is also possible after systemic absorption and metabolism of icodextrin.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes

制备方法与用途

生物活性

Glycogen 是糖酵解的中间产物和高能磷酸盐，它是人类、动物、真菌和细菌的能量储存形式。

靶点

Human Endogenous Metabolite

生产方法：

存在于肝和肌肉中，也存在于昆虫及低等植物中。可由肝脏用 30% 氢氧化钠处理，再加乙醇沉淀而制得。

文献信息

• [EN] FILM-FORMING COMPOSITION CONTAINING GELLAN GUM AND STARCH, AND APPLICATION IN SOFT CAPSULE<br/>[FR] COMPOSITION FILMOGÈNE CONTENANT DE LA GOMME GELLANE ET DE L'AMIDON, ET APPLICATION EN CAPSULE MOLLE<br/>[ZH] 含结冷胶和淀粉的成膜组合物及在软胶囊中应用
  申请人：SIRIO PHARMA CO LTD

  公开号：WO2021136169A1

  公开（公告）日：2021-07-08

  提供了淀粉成膜组合物，其包含：A、第一胶凝剂；B、淀粉；C、增塑剂；D、水；所述第一胶凝剂为具有两个凝胶温度的结冷胶，其中第一凝胶温度为51—75℃且第二凝胶温度为40℃—50℃。涉及食品或药物原料领域。该组合物用于制备软胶囊时胶皮强度、韧性和成型粘合方面明显优于现有技术，完全满足软胶囊工业化生产要求，可以作为软胶囊技术的备选替代。
• STILLAGE SOLIDS CONCENTRATION
  申请人：General Electric Company

  公开号：US20200080035A1

  公开（公告）日：2020-03-12

  Stillage solids concentration methods are disclosed wherein a solids concentration aid is added to a process stream mixture in a corn to ethanol process. The solids concentration aid may comprise a cationic polymer coagulant or flocculant or both, a starch based coagulant or flocculant or a biologically derived (i.e., plant or animal origin) coagulant or flocculant. Acrylamide/quaternary ammonium copolymers and homopolymeric polydiallyldimethyl ammonium chloride polymers are noteworthy examples of suitable solids concentration aids.
• FILM-FORMING COMPOSITION CONTAINING GELLAN GUM AND STARCH, AND APPLICATION IN SOFT CAPSULE
  申请人：SIRIO PHARMA CO., LTD.

  公开号：US20220226478A1

  公开（公告）日：2022-07-21

  Provided is a starch film-forming composition, comprising: A, a first gelling agent; B, starch; C, a plasticizer; D, water; wherein the first gelling agent is a gellan gum with two gel temperatures, wherein the first gel temperature is 51 to 75° C. and the second gel temperature is 40° C. to 50° C. The present application relates to the field of food or pharmaceutical raw materials. The composition is obviously superior to the prior art in terms of rubber strength, toughness and forming bonding when used in preparation of soft capsules, can fully meet the requirements for industrial production of soft capsules and can be used as an alternative in soft capsule technology.

表征谱图