A low molecular mass gelator can form soft solids in a variety of organic liquids and vegetable oils. These soft solids are generally called organogels. ...This study /examined organogel prepared/ using 12-hydroxystearic acid (12-HSA) as a gelator for soybean oil and investigated its characteristics as a controlled release formulation for lipophilic compounds. The release rate of ibuprofen, a model lipophilic compound, from organogel decreased with the increase of 12-HSA concentration in the formulation; however, the difference in the concentration of 12-HSA in the formulation did not affect the diffusivity of ibuprofen in the organogel. The erosion constant of organogel in the intestinal tract was examined by using simulated gastric fluid and intestinal fluid. Regardless of 12-HSA concentration in the formulation, organogel is very stable in the simulated gastric fluid. On the other hand, the erosion constant of organogel in the simulated intestinal fluid increased with the decreasing concentration of 12-HSA. Therefore, it is speculated that the difference in the release rate of ibuprofen among organogels with various concentrations of 12-HSA was mainly caused by the difference in the erosion rate. To characterize the organogel effect in vivo, ibuprofen was orally administered to rats in an aqueous suspension or organogel. Ibuprofen concentration in plasma rapidly increased after administration with an aqueous suspension, whereas organogel suppressed the rapid absorption. In conclusion, organogel is clearly useful as an oral controlled release formulation for lipophilic compounds.
/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/
/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",最小流量/。如果出现低血容量的迹象,使用0.9%的生理盐水(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/
/HUMAN EXPOSURE STUDIES/ The skin irritation potential of four antiperspirant prototype formulations ... containing 7% hydroxystearic acid was evaluated using 35 healthy adult volunteers between the ages of 8 and 65 years old (33 females; 2 males). The four formulations were applied to the back of each subject (in vertical rows over the scapulae areas) in occlusive and semiocclusive patch tests. Prior to patch application, test sites on the back were wiped with a pad containing 70% isopropyl alcohol. Each formulation was applied to a patch by wiping the antiperspirant stick across the patch approximately five times. The quantity of test material applied per patch application (occlusive and semiocclusive) was in the range of 0.05 to 0.1 g. The semiocclusive patches were applied to the left side of the back three times, each for 48 hours (total of three 48-hour applications per test site). Occlusive patches were applied to the right side of the back (total of three 24-hours applications per test site). Both semiocclusive and occlusive patches were reinforced with strips of tape. Following patch removal, subjects were instructed to rinse the test sites with warm water. Patches were also removed by laboratory personnel, and were not reapplied to anysite that was assigned a score of 2 or greater. Test sites were evaluated for skin irritation within 24 hours after patch removal according to the following scale: 0 (no visible erythema) to 3 (severe erythema, very intense redness). Reactions to semiocclusive patches were scored on days 4, 7, and 10; occlusive patch test reactions were scored on days 4, 6, and 8. ... Semioccluded patches produced reactions in as many as nine of the subjects, whereas occluded patches produced reactions in as many as 17 individuals. Only two reactions were noted in the semioccluded patch controls and only one in the occluded patch controls. Although the formulations reportedly contained the same concentration of Hydroxystearic Acid, there were small differences in the numbers of individuals reacting to each.
The distribution and metabolism of 12-hydroxystearic Acid were evaluated using 90 young male albino rats (Slonaker substrain of Wistar strain; weights = 43 to 83 g). The rats were divided into groups of six and fed the following diets over a period of 16 weeks: 20% corn oil (control diet); 1 % hydrogenated castor oil and 19% corn oil; and 10% hydrogenated castor oil and 10% corn oil. Laboratory chow accounted for 80% of each diet. The fatty acid composition of hydrogenated castor oil that was added to the diet was as follows: 86.5% 12-hydroxystearic acid, 10.3% nonoxygenated acids, and 3.2% 12-ketostearic acid. Therefore, the actual dietary concentrations of 12-hydroxystearic acid that were fed to experimental animals were 0.87% (in 1% hydrogenated castor oil diet) and 8.7% (in 10% hydrogenated castor oil diet). At 8 weeks after the initiation of feeding, half of the groups were fed a corn oil diet for the remainder of the 16-week study. ... Lipids were extracted from adipose tissue samples and carcasses (three rats on each diet) after 8, 12, and 16 weeks The number of rats on each experimental diet that were alive at 4, 8, 12, and 16 weeks was 33, 30, 12, and 6 rats, respectively. The number of control rats that were alive at 4, 8, 12, and 16 weeks was 15, 15, 12, and 6, respectively. ... 12-Hydroxystearic acid was deposited in abdominal fat, as well as other body lipids, along with its metabolites (hydroxypalmitic acid, hydroxymyristic acid, and hydroxylauric acid). The percent composition of hydrogenated castor oil-derived hydroxy fatty acids in rat lipids was 81% 12-hydroxystearic acid, 17% 10-hydroxypalmitic acid, 1.6% 8-hydroxymyristic acid, and 0.4% 6-hydroxylauric acid. The greatest content of hydroxy acids in lipids was 4.4% in abdominal fat obtained from rats after four weeks of feeding of the 8.7% 12-hydroxystearic acid diet. This concentration decreased during the following weeks, and, at 16 weeks, was less than 2% (approximately the same concentration that was detected in carcass lipids). Hydroxy acids (as % of dry carcass weight) increased during weeks 8 to 16 in rats on both diets, 0.87% and 8.7% 12-hydroxystearic acid. After the diet for half of the experimental rats was changed to corn oil (control diet) at 8 weeks, the tissue content of hydroxy fatty acids decreased rapidly.
When 12-hydroxystearate was added to the diet of one dog (weight not stated) in the amount of 2.2 g/day, 12-hydroxystearic acid accounted for 46% of the total fecal fatty acids. When the amount added to the diet was increased to 8.8 g/day, 12-hydroxystearic acid accounted for 60.2% of the total fecal fatty acids.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
12-羟基硬脂酸喂养正常狗后,并未产生脂肪泻,且其吸收量与未取代硬脂酸相似。
12-Hydroxystearic acid fed to normal dogs, steatorrhea was not produced & absorption in amt similar to that of unsubstituted stearic acid was observed.
The present invention relates to oligoesters and their use or the creation of additives. Oligoester containing additives and/or oligoesters themselves may be used for formulating pharmaceutical preparations, cosmetics or personal care products such as shampoos and conditioners. These oligoesters are particularly useful for the creation of multi-purpose additives that can impart conditioning, long substantivity and/or UV protection. Individual oligoesters and oligoester mixtures are described.
[EN] LYMPHATIC SYSTEM-DIRECTING LIPID PRODRUGS<br/>[FR] PROMÉDICAMENTS LIPIDIQUES ORIENTANT VERS LE SYSTÈME LYMPHATIQUE
申请人:ARIYA THERAPEUTICS INC
公开号:WO2019046491A1
公开(公告)日:2019-03-07
The present invention provides lymphatic system-directing lipid prodrugs, pharmaceutical compositions thereof, methods of producing such prodrugs and compositions, as well as methods of improving the bioavailability or other properties of a therapeutic agent that comprises part of the lipid prodrug. The present invention also provides methods of treating a disease, disorder, or condition such as those disclosed herein, comprising administering to a patient in need thereof a provided lipid prodrug or a pharmaceutical composition thereof.
[EN] VALSARTAN DERIVATIVES CARRYING NITROGEN OXIDE DONORS FOR THE TREATMENT OF VASCULAR AND METABOLIC DISEASES<br/>[FR] DÉRIVÉS DE VALSARTAN PORTANT DES DONNEURS D'OXYDE D'AZOTE DANS LE TRAITEMENT DE MALADIES VASCULAIRES ET MÉTABOLIQUES
申请人:CARDIOLYNX AG
公开号:WO2011131613A1
公开(公告)日:2011-10-27
Nitrate esters and diazeniumdiolate derivatives of valsartanamide are described. They have valuable properties in the treatment of vascular and metabolic diseases.
硝酸酯和缬沙坦胺的重氮二醇酯衍生物被描述。它们在治疗血管和代谢性疾病方面具有宝贵的特性。
N-(HETERO)ARYL-PYRROLIDINE DERIVATIVES OF PYRAZOL-4-YL-PYRROLO[2,3-d]PYRIMIDINES AND PYRROL-3-YL-PYRROLO[2,3-d]PYRIMIDINES AS JANUS KINASE INHIBITORS
申请人:Rodgers James D.
公开号:US20100298334A1
公开(公告)日:2010-11-25
The present invention relates to N-(hetero)aryl-pyrrolidine derivatives of Formula I:
which are JAK inhibitors, such as selective JAK1 inhibitors, useful in the treatment of JAK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer.
Schmidt reaction by sulfonium ions is described. General primary, secondary, and tertiary alkyl azides were converted to the corresponding carbonyl or imine compounds without any trace of the activators. This bond scission reaction through 1,2-migration of C–H and C–C bonds was accessible to the one-pot substitution reaction.