果阿胶

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 果阿胶
• 中文别名: 瓜尔胶；瓜尔豆胶；胍尔豆胶；关华豆胶
• 英文名称: Disodium;[[[5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]oxy-methoxyphosphoryl]oxy-oxidophosphoryl] hydrogen phosphate
• 英文别名: disodium;[[[5-(6-aminopurin-9-yl)-3-hydroxyoxolan-2-yl]oxy-methoxyphosphoryl]oxy-oxidophosphoryl] hydrogen phosphate
• 化学式: C10H14N5Na2O12P3
• 分子量: 535.15
• InChiKey: LUSTYMNNBDCASM-UHFFFAOYSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -7.24
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  254
• 氢给体数：
  3
• 氢受体数：
  16

ADMET

毒理性

• 毒性总结

识别和用途：瓜尔豆胶是一种白色至淡黄色的自由流动粉末，无味，口感平淡。它有多种用途，包括作为保护胶体、稳定剂、增稠剂和成膜剂用于奶酪、沙拉酱、冰淇淋、汤；作为片剂制剂中的粘合剂和崩解剂；在药物果冻制剂中使用；在纳米颗粒悬浮液、乳液、乳膏、面霜、牙膏中使用；在采矿工业中作为絮凝剂、过滤剂；在污水处理中作为助凝剂。它通常以部分水解的形式用作膳食纤维。它也用于水力压裂作为凝胶剂。人类暴露和毒性：瓜尔豆胶被认为是相当无毒的。五名志愿者每天服用一克瓜尔豆粉胶囊，持续10天，没有明显的影响。富含不可吸收碳水化合物（“纤维”）如瓜尔豆胶的饮食被提倡用于治疗非胰岛素依赖型糖尿病（NIDDM）。8名患有NIDDM的成年人至少连续16周每天摄入30克瓜尔豆胶，血液学、肝功能或肾功能没有变化。血清学筛查显示脂质、蛋白质或矿物质代谢没有变化，电解质平衡也没有变化。结论是，每天摄入30克瓜尔豆胶，长期服用没有严重后果。有过敏反应导致并发症的案例。瓜尔豆胶曾导致食管阻塞。一例死亡归因于使用一种瓜尔豆胶片剂产品，该产品在食道中膨胀，间接导致并发症，导致死亡。一名男性在食用含有瓜尔豆胶的代餐“Gerlina”后几分钟内出现严重的过敏性反应：胸痛和上腹痛、突然虚弱、呼吸急促和循环衰竭。皮肤测试和放射变应原吸附测试对代餐和瓜尔豆胶、角豆胶呈阳性，显示IgE介导的机制。使用肾上腺素和皮质类固醇注射治疗有效。瓜尔豆胶在人类胚胎肺细胞（WI-38）中引起了染色体畸变。动物研究：在13周内，给每性别/种类的10只大鼠和小鼠喂食含有0、6,300、12,500、25,000、50,000或100,000 ppm瓜尔豆胶的饮食，没有观察到与化合物相关的临床体征或组织病理学效应。在给大鼠和小鼠喂食含有25,000或50,000 ppm瓜尔豆胶的饮食103周后，瓜尔豆胶并未表现出致癌性。在20周的小鼠和40周的大鼠之后，高剂量雌性的平均体重低于未处理对照组。没有观察到与化合物相关的临床体征或对生存的负面影响。给药的大鼠和小鼠的饲料消耗量低于对照组。在没有代谢激活的情况下进行测试时，瓜尔豆胶对酿酒酵母D-3具有致突变性，但对鼠伤寒沙门氏菌TA 1530或G-46则无致突变性。瓜尔豆胶不具有致畸性。在雄性和雌性大鼠在交配前13周、交配期间和整个妊娠期间自由摄取含有0、1、2、4、7.5或15%瓜尔豆胶的饲料，对胎儿发育或性别分布没有与化合物相关的影响。

IDENTIFICATION AND USE: Guar gum is a white to yellowish-white free flowing powder that is odorless and has a bland taste. It has many uses including as a protective colloid, stabilizer, thickening and film forming agent for cheese, salad dressings, ice cream, soups; as binding and disintegrating agent in tablet formulations; in pharmaceutical jelly formulations; in nanoparticle suspensions, emulsions, lotions, creams, toothpastes; in the mining industry as a flocculants, as a filtering agent; and in water treatment as a coagulant aid. It is often used as a dietary fiber in the partially hydrolyzed form. It is also used in hydraulic fracturing as a gelling agent. HUMAN EXPOSURE AND TOXICITY: Guar gum is considered fairly non-toxic. Five volunteers ingested 1 g of guar flour in a capsule per day for 10 days without any apparent effect. The use of diets rich in unabsorbable carbohydrate ("fiber") such as guar gum has been advocated for the treatment of noninsulin-dependent diabetes mellitus (NIDDM). 8 adults with NIDDM consumed at least 30 grams of guar gum for at least 16 weeks without any change in hematologic, hepatic, or renal function. Serologic screening revealed no change in lipid, protein or mineral metabolism, and no change in electrolyte balance. It is concluded that consumption of 30 grams of guar gum per day for prolonged periods is without serious consequences. There are cases of complications due to allergic reactions to guar gum. Guar gum was blamed in causing esophageal obstruction. A death has been attributed to the use of one guar gum tablet product, which apparently swelled in the esophagus, indirectly resulting in complications that caused the fatality. A male presented severe anaphylactic reaction: chest and epigastric pain, sudden weakness, breath shortness and circulatory collapse a few minutes after eating "Gerlina", a meal substitute which contains guar gum. Skin tests and radioallergosorbent tests were positive for the meal substitute, and for guar and carob gums with evidence of an IgE-mediated mechanism. Treatment with shots of adrenaline and corticoids was effective. . Guar gum caused chromosome aberrations in human embryonic lung cells (WI-38). ANIMAL STUDIES: No compound related clinical signs or histopathological effects were observed in rats and mice (10 per sex/per species) fed Diets containing 0, 6,300, 12,500, 25,000, 50,000, or 100,000 ppm guar gum for 13 weeks. Guar gum was not carcinogenic in rats or mice fed diets containing 25,000 or 50,000 ppm guar gum for 103 weeks. After week 20 in mice and week 40 in rats, mean body weights of high-dose females were lower than those of the untreated controls. No compound-related clinical signs or adverse effects on survival were observed. Feed consumption by dosed rats and dosed mice of either sex was lower than that of the controls. When tested without metabolic activation, guar gum was mutagenic for Saccharomyces cerevisiae D-3, but not for Salmonella typhimurium TA 1530 or G-46. Guar gum is not teratogenic. There was no compound-related effect on fetal development or sex distribution in male and female rats with 0, 1, 2, 4, 7.5 or 15% guar gum available in feed ad lib. for 13 weeks before mating, during mating and throughout gestation.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

预计将开发表面改性的瓜尔胶纳米颗粒（GGNP），并带有叶酸（FA）负载甲氨蝶呤（MTX），以专门针对结肠。通过乳液交联法已制备了负载MTX的FA功能化GGNP（MTX-FA-GGNP）。将这些表面改性的纳米颗粒与未改性的负载MTX的GGNP（MTX-GGNP）进行了比较。对开发配方的粒径和粒径分布、zeta电位、差示扫描量热法（DSC）、释放曲线和摄取研究进行了评估。纳米颗粒的平均直径为325纳米，多分散性指数（PDI）为0.177，表明颗粒单一分散。颗粒的zeta电位为-36.9 mV。与MTX-GGNP相比，MTX-FA-GGNP对Caco 2细胞的生长抑制百分比更高，表明是叶酸受体介导的摄取。MTX-GGNP在上消化道中保护MTX的释放，而在pH 6.8的模拟结肠液中MTX的最大释放发生。体内摄取研究显示纳米颗粒配方在结肠中的优先摄取。这些研究表明，MTX-FA-GGNP有望针对过度表达叶酸受体的结直肠癌。这种原型配方具有双重优势，即在结肠中释放药物的趋势，并且在结直肠癌的条件下，由于叶酸受体的过度表达，它可以更好地定位和靶向，从而改善治疗效果。/改性瓜尔胶纳米颗粒/

It was envisaged to develop surface modified Guar Gum Nanoparticles (GGNP) with Folic acid (FA) charged with methotrexate (MTX) to target the colon specifically. The MTX loaded FA functionalized GGNP (MTX-FA-GGNP) have been prepared by emulsion crosslinking method. These surface modified nanoparticles were compared with unmodified MTX loaded GGNP (MTX-GGNP). The developed formulations were evaluated for size and size distribution, zeta potential, Differential Scanning Calorimetry (DSC), release profile and uptake studies. The nanoparticles have been found to have average size of 325 nm in diameter having polydispersity index (PDI) 0.177 indicating mono-disperse particles. The zeta potential of the particles was found to be -36.9 mV. The percent growth inhibition of Caco 2 cells with MTX-FA-GGNP was found to be better than MTX-GGNP indicating folate receptor mediated uptake. The MTX-GGNP protects the release of MTX in upper gastrointestinal tract while maximum release of MTX occurred in simulated colonic fluids of pH 6.8. The in vivo uptake studies revealed preferential uptake of nanoparticles formulation in the colon. These studies provide evidences that MTX-FA-GGNP holds promise to address colorectal cancer over-expressing folate receptors. This prototype formulation enjoys dual advantage of having propensity to release the drug in the colon and in the conditions of colorectal carcinoma; it could be better localized and targeted with improved therapy due to over-expression of folate receptors. /Modified Guar Gum Nanoparticles/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

5-氟尿嘧啶(5-FU)化疗常伴有腹泻。我们比较了两种基于5-FU的方案以及乳酸杆菌和纤维补充对治疗耐受性的影响。确诊为结直肠癌的患者(n=150)被随机分配接受每月一次的5-FU和亚叶酸钙静脉注射（梅奥方案）或每两个月一次的5-FU静脉注射加持续输注（简化德格拉蒙方案），持续24周作为术后辅助治疗。根据随机分配，研究参与者在化疗期间是否接受乳酸杆菌GG补充剂（每天1-2 x 10(10)）和纤维（每天11克瓜尔胶）。接受乳酸杆菌的患者3级或4级腹泻较少（22%对37%，P=0.027），报告的腹部不适较少，需要的医院护理较少，因肠毒性导致的化疗剂量减少也较少。没有检测到与乳酸杆菌相关的毒性。瓜尔胶补充剂对化疗耐受性没有影响。与梅奥方案相比，简化德格拉蒙方案与较少的3级或4级不良反应（45%对89%）和较少的腹泻相关。我们得出结论，乳酸杆菌GG补充剂具有良好的耐受性，可能减少与基于5-FU的化疗相关的严重腹泻和腹部不适的频率。

5-Fluorouracil (5-FU)-based chemotherapy is frequently associated with diarrhoea. We compared two 5-FU-based regimens and the effect of Lactobacillus and fibre supplementation on treatment tolerability. Patients diagnosed with colorectal cancer (n=150) were randomly allocated to receive monthly 5-FU and leucovorin bolus injections (the Mayo regimen) or a bimonthly 5-FU bolus plus continuous infusion (the simplified de Gramont regimen) for 24 weeks as postoperative adjuvant therapy. On the basis of random allocation, the study participants did or did not receive Lactobacillus rhamnosus GG supplementation (1-2 x 10(10) per day) and fibre (11 g guar gum per day) during chemotherapy. Patients who received Lactobacillus had less grade 3 or 4 diarrhoea (22 vs 37%, P=0.027), reported less abdominal discomfort, needed less hospital care and had fewer chemotherapy dose reductions due to bowel toxicity. No Lactobacillus-related toxicity was detected. Guar gum supplementation had no influence on chemotherapy tolerability. The simplified de Gramont regimen was associated with fewer grade 3 or 4 adverse effects than the Mayo regimen (45 vs 89%), and with less diarrhoea. We conclude that Lactobacillus GG supplementation is well tolerated and may reduce the frequency of severe diarrhoea and abdominal discomfort related to 5-FU-based chemotherapy.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

简介：益生元对肠道微生物群组成产生积极影响，从而改善肠道功能。这些特性可能对治疗便秘有益。目标：本研究评估了益生元菊粉/部分水解瓜尔胶混合物（I-PHGG）在治疗女性便秘方面的耐受性和有效性，以及其对肠道微生物群组成和短链脂肪酸产生的影响。方法：我们的研究招募了60名便秘的女性健康工作者志愿者。参与者的每周排便次数少于3次。志愿者被随机分配接受益生元或安慰剂治疗。治疗包括3周的补充，每天15克I-PHGG（纤维组）或麦芽糊精（安慰剂组）。通过每日问卷记录和每周访谈评估腹部不适、腹胀、大便一致性和排便情况。通过实时PCR和气相色谱分别评估粪便细菌种群和短链脂肪酸的变化。结果：纤维组和安慰剂组的每周排便频率和患者满意度都有所增加，但差异无统计学意义。纤维组中的总梭菌数量显著减少（p = 0.046），而安慰剂组中增加（p = 0.047）。粪便短链脂肪酸谱没有变化。结论：I-PHGG的消耗在便秘女性中产生了与安慰剂相当的疗效，并且通过减少Clostridium属的有害细菌数量，对肠道微生物群产生了额外的保护作用。/部分水解瓜尔胶/

INTRODUCTION: Prebiotics positively affect gut microbiota composition, thus improving gut function. These properties may be useful for the treatment of constipation. OBJECTIVES: This study assessed the tolerance and effectiveness of a prebiotic inulin/partially hydrolyzed guar gum mixture (I-PHGG) for the treatment of constipation in females, as well as its influence on the composition of intestinal microbiota and production of short chain fatty acids. METHODS: Our study enrolled 60 constipated female health worker volunteers. Participants reported less than 3 bowel movements per week. Volunteers were randomized to treatment with prebiotic or placebo. Treatment consisted of 3 weeks supplementation with 15 g/d IPHGG (fiber group) or maltodextrin (placebo group). Abdominal discomfort, flatulence, stool consistency, and bowel movements were evaluated by a recorded daily questionnaire and a weekly interview. Changes in fecal bacterial population and short chain fatty acids were assessed by real-time PCR and gas chromatography, respectively. RESULTS: There was an increased frequency of weekly bowel movements and patient satisfaction in both the fiber and placebo groups with no significant differences. Total Clostridium sp significantly decreased in the fiber group (p = 0.046) and increased in the placebo group (p = 0.047). There were no changes in fecal short chain fatty acid profile. CONCLUSIONS: Consumption of I-PHGG produced clinical results comparable to placebo in constipated females, but had additional protective effects on gut microbiota by decreasing the amount of pathological bacteria of the Clostridium genera. /partially hydrolyzed guar gum/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

目标：估计部分水解瓜尔胶（PHGG）对女性受试者因摄入足够量的麦芽糖醇或乳糖醇而引发的暂时性腹泻的抑制效果。 设计：首先，分别估计每个受试者引发暂时性腹泻的麦芽糖醇和乳糖醇的最小剂量水平。给每个受试者依次增加5克，从10克到45克，直到出现腹泻。此后，观察在受试者摄入5克PHGG和最小剂量水平的麦芽糖醇或乳糖醇混合物后对腹泻的抑制效果。 地点：长崎市西博德公共卫生营养实验室，营养与健康科学系。 受试者：34名正常女性受试者（年龄21.3±0.9岁；体重49.5±5.3公斤）。 主要结果测量：摄入麦芽糖醇或乳糖醇引起的腹泻发生率，以及通过添加PHGG对腹泻的抑制比率。 结果：摄入最多45克的麦芽糖醇，34名受试者中有29名（85.3%）出现腹泻，而摄入乳糖醇则在100%的受试者中引起腹泻。在麦芽糖醇引起的腹泻中，有28名受试者中的10名通过向最小剂量引起的腹泻中添加5克PHGG得到改善，而乳糖醇引起的腹泻中有19名受试者中的7名得到改善。添加10克PHGG强烈抑制了由麦芽糖醇引起的腹泻，累积抑制率为82.1%（23/28）。 结论：由摄入麦芽糖醇或乳糖醇引起的暂时性腹泻通过添加PHGG得到了明显的抑制。这些结果强烈表明，由摄入足够量的非消化糖替代品引起的腹泻可以通过添加膳食纤维来抑制。/部分水解瓜尔胶/

OBJECTIVES: To estimate the suppressive effect of partially hydrolyzed guar gum (PHGG) on transitory diarrhea induced by ingestion of a sufficient amount of maltitol or lactitol in female subjects. DESIGN: The first, the minimal dose level of maltitol and lactitol that would induce transitory diarrhea was estimated separately for each subject. Individual subject was administered a dose that increased by 5 g stepwise from 10 to 45 g until diarrhea was experienced. Thereafter, the suppressive effect on diarrhea was observed after each subject ingested a mixture of 5 g of PHGG and the minimal dose level of maltitol or lactitol. SETTING: Laboratory of Public Health Nutrition, Department of Nutrition and Health Sciences, Siebold University of Nagasaki. SUBJECTS: Thirty-four normal female subjects (21.3+/-0.9 years; 49.5+/-5.3 kg). MAIN OUTCOME MEASUREMENT: Incidence of diarrhea caused by the ingestion of maltitol or lactitol and the ratio of suppression achieved by adding PHGG for diarrhea. RESULTS: The ingestion of amounts up to 45 g of maltitol, diarrhea caused in 29 of 34 subjects (85.3%), whereas the ingestion of lactitol caused diarrhea in 100%. The diarrhea owing to maltitol was improved in 10 of 28 subjects by the addition of 5 g of PHGG to minimal dose-induced diarrhea, and that owing to lactitol was in seven of 19 subjects. Adding 10 g of PHGG strongly suppressed the diarrhea caused by maltitol, and the cumulative ratio was 82.1% (23/28). CONCLUSION: The transitory diarrhea caused by the ingestion of maltitol or lactitol was clearly suppressed by the addition of PHGG. These results strongly suggest that diarrhea caused by the ingestion of a sufficient amount of non-digestible sugar substitute can be suppressed by the addition of dietary fiber. /partially hydrolyzed guar gum/

来源:Hazardous Substances Data Bank (HSDB)