Rat intestinal maltase was shown to be active against isomalt, alpha-O-D-glucopyranosyl-1,6-D-sorbitol, and alpha-O-D-glucopyranosyl-1,6-D-mannitol, but the rates of hydrolysis were slow. The ratio of the rates of hydrolysis of sucrose, isomaltulose, and isomalt by rat intestinal alpha-glucosidases was 100:30:12. Similarly, sucrose was hydrolysed about 20 times faster than alpha-O-D-glucopyranosyl-1,6-D-sorbitol or alpha-O-D-glucopyranosyl-1,6-D-mannitol by disaccharidases from the small intestine of the pig, and the relative rates of hydrolysis of maltose, sucrose, isomaltulose and isomalt by human intestinal alpha-glucosidases were 100:25:11:2.
The fate of isomalt in the gastrointestinal tract of female rats that had been adapted to the compound was investigated by increasing its dietary concentration from 10% to 34.5% over a period of 3-4 weeks. After administration of 1.7 g isomalt in 5 g feed, the contents of the stomach, small intestine, cecum, and large intestine were examined at intervals up to 6 hr. From the content of alpha-O-D-glucopyranosyl-1,6-D-sorbitol, alpha-O-D-glucopyranosyl-1,6-D-mannitol, sorbitol, mannitol, and sucrose found in these organs, the authors concluded that alpha-O-D-glucopyranosyl-1,6-D-sorbitol and alpha-O-D-glucopyranosyl-1,6-D-mannitol were only partially hydrolyzed by the carbohydrases in the small intestine, while a substantial proportion of these compounds reached the cecum where further hydrolysis of glycosidic bonds occurred. Fermentation of the liberated hexitols occurred in the cecum, which was enlarged, and only small amounts of alpha-O-D-glucopyranosyl-1,6-D-sorbitol, alpha-O-D-glucopyranosyl-1,6-D-mannitol, and hexitols reached the large intestine.
Dental caries and periodontal disease are wide-spread oral illnesses whose etiology is intimately associated with the consumption of carbohydrate sweeteners....Human clinical trials and several animal experiments have shown promising clinical results obtained by replacing sucrose with certain sugar alcohols (polyols). Among the sugar alcohols, the best results so far have been obtained with xylitol, which is chemically a pentitol containing five carbon atoms. Chewing gums containing xylitol have been shown to be strong instruments against caries in caries-active age-groups and in high-risk subjects. More research is needed to assess the ability of mixtures of xylitol with sorbitol, palatinit, maltitol, other sugar alcohols, and intense sweeteners to prevent oral plaque diseases. Although thorough clinical trials on the relationship between carbohydrate sweeteners and periodontal diseases have not been performed, the available data indicate that dietary polyols may have a restricted dampening effect on periodontal and gingival inflammations.
/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 as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on 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. /Higher alcohols (>3 carbons) and related compounds/
/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 necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . Monitor for pulmonary edema 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. Administer activated charcoal ... . /Higher alcohols (>3 carbons) and related compounds/
/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 ... . 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 (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Consider vasopressors if patient is hypotensive with a normal fluid volume. Watch for signs of fluid overload ... . Monitor for signs of hypoglycemia (decreased LOC, tachycardia, pallor, dilated pupils, diaphoresis, and/or dextrose strip or glucometer readings below 50 mg) and administer 50% dextrose if necessary ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Higher alcohols (>3 carbons) and related compounds/
/HUMAN EXPOSURE STUDIES/ The polyol isomalt (Palatinit) is a well established sugar replacer. The impact of regular isomalt consumption on metabolism and parameters of gut function in nineteen healthy volunteers was examined in a randomised, double-blind, cross-over trial with two 4-week test periods. Volunteers received 30 g isomalt or 30 g sucrose daily as part of a controlled diet. In addition to clinical standard diagnostics, biomarkers and parameters currently discussed as risk factors for CHD, diabetes or obesity were analysed. Urine and stool Ca and phosphate excretions were measured. In addition, mean transit time, defecation frequency, stool consistency and weight were determined. Consumption of test products was affirmed by the urinary excretion of mannitol. Blood lipids were comparable in both phases, especially in volunteers with hyperlipidaemia, apart from lower apo A-1 (P=0.03) for all subjects. Remnant-like particles, oxidised LDL, NEFA, fructosamine and leptin were comparable and not influenced by isomalt. Ca and phosphate homeostasis was not affected. Stool frequency was moderately increased in the isomalt phase (P=0.006) without changes in stool consistency and stool water. This suggests that isomalt is well tolerated and that consumption of isomalt does not impair metabolic function or induce hypercalciuria. ...
The in vivo metabolism of isomalt in the large intestine was simulated in an in vitro fermentation study to investigate its degradation using chyme from pigs as a basic substrate additionally inoculated with feces. In the first week, the fermentation of isomalt (3.65%) by non-adapted microflora was investigated. In the second week, isomalt fermentation by adapted microflora taken from pigs fed a basic diet supplemented with isomalt was studied. In the third week, both /non-adapted and adapted/ flora were studied in fermentation experiments with a high concentration of isomalt (7.30%). Isomalt was degraded to lactic acid, volatile fatty acids, and gases (CO2, CH4, and hydrogen). ...
Fistulated and normal pigs were fed 10% sucrose between meals, 5 or 10% isomalt between meals, or 10% isomalt with meals. The passage and absorption rate of these substances were determined at the terminal ileum (10 pigs per treatment) or over the whole distance of the digestive tract (4 pigs per treatment). Ten percent sucrose was completely digested and absorbed in the small intestine. In the 3 isomalt treatments, 61-64% of the ingested compound passed the terminal ileum in the form of intact isomalt plus free sorbitol, free mannitol, and free glucose. None of these sugars were excreted in the feces, indicating that isomalt and its constituents passing the terminal ileum are completely broken down in the large intestine.
Renal clearance studies were conducted in adult female rats (250 g b.w.) infused with 1.8 g isomalt, alpha-O-D-glucopyranosyl-1,6-D-sorbitol, or alpha-O-D-glucopyranosyl-1,6-D-mannitol over a period of 3 hours. Maximum plasma concentrations of 25 mM were obtained. These compounds were readily cleared and urinary concentrations of up to 100 mg/mL were recorded, which compares with a maximum urinary concentration of 0.6 mg/mL in rats receiving 5 g isomalt per day orally. After the infusion of either isomalt or alpha-O-D-glucopyranosyl-1,6-D-sorbitol, free sorbitol was not detected in blood or urine, and blood glucose concentrations were unchanged, demonstrating the metabolic inertness of these disaccharide alcohols. From the infusion and excretion rates and the plasma concentrations that were observed, the authors concluded that alpha-O-D-glucopyranosyl-1,6-D-sorbitol is distributed in extracellular water, but does not reach the intracellular compartments.
When isomalt was fed to rats for several weeks it was observed that fecal excretion declined steadily, while the cecum enlarged. The authors concluded that this resulted from adaptation and metabolism by the gut microflora. Similarly, during a 17-day feeding period in which 6 female rats received 3.5 g isomalt daily, the fecal content fell from 25% of the dose at the beginning to 1% at the end.
Sequential Removal of Monosaccharides from the Reducing End of Oligosaccharides. 2. Fundamental Studies of a Reaction between Hydrazino Compounds and Sugars Having a Glycosyl Moiety on a Carbon Atom Adjacent to a Carbonyl Group
摘要：
Hydrazine and certain hydrazino derivatives react with sugars having a glycosidic substituent, where the glycosyl moiety is located on a carbon atom adjacent to an aldehyde or keto group of the aglycon, resulting in cleavage of the glycosidic linkage. The reaction proceeds whether the glycon is of the alpha or beta configuration. The released glycosyl moiety, in the presence of excess hydrazino compound, reacts further to give a hydrazone derivative. Removal of the hydrazone group gives the reducing sugar derived from the glycon.
Selective and Scalable Synthesis of Sugar Alcohols by Homogeneous Asymmetric Hydrogenation of Unprotected Ketoses
作者：Daniel J. Tindall、Steffen Mader、Alois Kindler、Frank Rominger、A. Stephen K. Hashmi、Thomas Schaub
DOI：10.1002/anie.202009790
日期：2021.1.11
with none to low stereoselectivities. Now, we present a homogeneous system based on commercially available components, which not only increases the overall yield, but also allows a wide range of unprotected ketoses to be diastereoselectively hydrogenated. Furthermore, the system is reliable on a multi‐gram scale allowing sugar alcohols to be isolated in large quantities at high atom economy.
[EN] TYROSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE TYROSINE KINASE
申请人：MERCK SHARP & DOHME
公开号：WO2011084402A1
公开（公告）日：2011-07-14
The present invention relates to pyridazin-4(1H)-one derivatives, that are useful for treating cellular proliferative diseases, for treating disorders associated with MET activity, and for inhibiting the receptor tyrosine kinase MET. The invention also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.
The present invention relates to an improved process for the manufacture of Isomaltitol by hydrogenation of Isomaltulose. According to the process, a solution of Isomaltulose having a concentration in the range of between 20% to 50% by weight, is hydrogenated at a temperature in the range of between 80.degree. C. to 130.degree. C., using a catalyst selected from Ruthenium, Nickel and mixtures thereof on an inert support at a pressure below 50 atmospheres, the pH being maintained in the range of 3 to 8. The resulted product is substantially free from other polymers, Among the advantages of the process it should be mentioned the fact that it enables to achieve the desired ratio between the two isomers .alpha.-Glucopyranosyl-1,1-Mannitol (GPM) and .alpha.-Glucopyranosyl-1,6-D-Sorbitol (GPS).
A detergent or cleaning agent comprising a dispersion of solid particles in a dispersion agent wherein the dispersion is comprised of, based on the total weight of the dispersion (a) from 10 to 65 wt % dispersing agent and (b) from 30 to 90 wt % of dispersed materials, wherein the dispersed materials are comprised of from 0.1 to 50 wt % of an anionic and/or cationic and/or amphoteric polymer based on the total weight of the dispersed materials. This composition can be easily formed into tablets.
