参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 美国食品药品监督管理局批准的药物标签用于研究药物诱导的肝损伤，《药物发现今日》，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按人类发展药物诱导肝损伤风险排名的最大参考药物清单。《药物发现今日》2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
◉ Summary of Use during Lactation:Because sevelamer is not orally absorbed, sevelamer does not reach the breastmilk or adversely affect the breastfed infant after maternal administration. A suspension of sevelamer has been added directly to breastmilk to lower the phosphorus concentration of milk. This could be a useful maneuver for breastmilk use in infants with renal impairment; however, clinical use has not been reported. In addition to lowering average phosphorus content by 65% to over 80%, the calcium content of breastmilk was reduced by almost as much and the casein content also decreased somewhat. With sevelamer hydrochloride, the chloride content increased by 60% and the pH changed from 6.8 to 7.8, although pH appears to rebound over time. Addition of large amounts of sevelamer to artificial formula also lowers the copper, magnesium, manganese, potassium, sulfur and zinc concentrations by about 20%. Similar reductions might occur with breastmilk.
◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
Not absorbed following oral administration, however no absorption studies have been performed in patients with renal disease. Sevelamer may bind to dietary phosphates and prevent its gastrointestinal absorption when sevelamer is administered in combination with food.
Six rats received a single oral dose of ((3)H)sevelamer and six rats were pretreated with unlabelled sevelamer in the diet for 28 days followed by a single dose of ((3)H)sevelamer on day 29. Total urine and feces were collected at intervals up to 72 hours post dose, and tissues were obtained at the time of sacrifice. In the clinical trial, subjects received a single oral dose of (14)C sevelamer following 28 days of pretreatment with unlabelled sevelamer. Blood, urine and feces samples were collected at intervals up to 96 hours. In the rat study, no significant urinary excretion of radioactivity was observed. The average recovery of radioactivity in the feces was 98% in the single-dose group and greater than 100% in the group pretreated with unlabelled sevelamer for 28 days. A total of less than 0.1% of the dose was found in the tissues. In the human study, no detectable amount of (14)C was found in the blood of any subject at any time. The majority of subjects had no detectable amounts of (14)C recovered in the urine. In subjects where (14)C was recovered in the urine, less than 0.02% was detected, a level equivalent to the free (14)C detected in the [(14)C]sevelamer preparation. On average, greater than 99% of the administered dose was recovered in the feces of the subjects. These studies demonstrate that sevelamer is a non-absorbed compound.
A mass balance study using (14)C-sevelamer hydrochloride in 16 healthy male and female volunteers showed that sevelamer hydrochloride is not systemically absorbed. No absorption studies have been performed in patients with renal disease.
The present invention relates to a process for the preparation of sevelamer, in particular sevelamer hydrochloride and sevelamer carbonate/bicarbonate, by means of a process that allows sevelamer to be obtained with good yields and using conventional reactors, without requiring to use specific and expensive equipment.
The present invention relates to crosslinked polyamine particles and/or pharmaceutical compositions comprising, at least in part, crosslinked polyamine particles and aggregates of such particles (including cured aggregates of crosslinked polyamine particles). The compositions may be in the form of tablets comprising, for example, particles larger than 500 μm particles and used for treating patients, for example, patients with hyperphosphatemia.
Process For The Preparation Of Colesevelam Hydrochloride
申请人：Patel Mahendra R.
公开号：US20150080532A1
公开（公告）日：2015-03-19
A novel process of manufacturing colesevelam hydrochloride including the steps of alkylating polyallylamine with n-decylbromide and 6-bromohexyl trimethyl ammonium bromide, followed by cross-linking the alkylated polyallylamine with epichlorohydrin in an aqueous medium, and adding a suitable chloride ion source to obtain colesevelam hydrochloride.
The present invention relates to crosslinked polyamine particles and/or pharmaceutical compositions comprising, at least in part, crosslinked polyamine particles and aggregates of such particles (including cured aggregates of crosslinked polyamine particles). The compositions may be in the form of tablets comprising, for example, particles larger than 500 μm, and used for treating patients, for example, patients with hyperphosphatemia.
Oral pharmaceutical composition for drugs with a high-dosage regimen
申请人：LABORATORIOS RUBIO, S.A.
公开号：US10413568B2
公开（公告）日：2019-09-17
The present invention relates to an oral pharmaceutical composition for drugs with a high dosage regimen, specifically, ion exchange resins and bulk-forming laxatives. Said composition comprises the combination of a liquid oily component and a texturizing agent, giving the composition good organoleptic properties that allow taking drugs with a high dosage regimen without the usual problems associated with their poor palatability. The invention also relates to a method for preparing said composition and to the use thereof for the treatment of various pathologies. Furthermore, the invention also relates to an adduct formed between a polyol and an ion exchange resin, to a method for preparing it, and to the use thereof to improve resin palatability.
