奥尔梅沙坦美多克索米尔与β-环氧德克斯衍生物的宿主-客人相互作用研究
Minodora Andor1, Claudia Temereancă2, Laura Sbârcea3,4
1Faculty of Medicine, "Victor Babeş" University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041 Timisoara, Romania.
Molecules (Basel, Switzerland)
|May 25, 2024
概括
将olmesartan medoxomil (OLM) 封装成甲基化环极素,特别是随机甲基化β-环极素 (RM-β-CD),显著提高了其水溶性差. 这种分子封装改善了OLM.
科学领域:
- 制药科学 制药科学
- 物理化学 物理化学
- 材料科学 材料科学 材料科学
背景情况:
- 奥尔梅沙坦美多克索米尔 (OLM) 是一种用于高血压的血管激素II受体对抗剂.
- 较差的水溶性限制了OLM的生物可用性和治疗疗效.
- 循环德克斯 (CDs) 正在探索改善药物的溶解性和输送.
研究的目的:
- 提高OLM的可溶性和生物制药特征.
- 调查OLM在随机甲基化β-环氧化 (RM-β-CD) 和2,3,6-三-O-甲基) -β-环氧化 (TM-β-CD) 中的封装.
- 为了描述由此产生的超分子纳入复合体.
主要方法:
- 阶段溶解性研究,以确定静态度和稳定性.
- 热分析技术 (TG,DTG) 和光谱方法 (PXRD,UATR-FTIR,紫外线光谱学).
- 分子建模和和可溶性研究.
主要成果:
- 在OLM和RM-β-CD和TM-β-CD之间形成1:1的纳入复合体.
- OLM/RM-β-CD复合体表现出更高的表面稳定性.
- 二元系统的物理化学特性与母化合物有所不同,证实了复杂的形成.
- 在RM-β-CD中对OLM的分子封装显著增加了其溶解性.
结论:
- 甲基化环氧,特别是RM-β-CD,有效地提高了OLM的溶解性.
- OLM/RM-β-CD超分子引体显示出开发新型药物配方的潜力.
- 增强的溶解性表明未来的OLM药物输送系统的生物可用性得到改善.
相关概念视频
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
198
Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
198
Dose-Response Relationship: Potency and Efficacy
4.4K
The potency of a drug is the measure of its ability to produce a biological response and can be compared by looking at the half-maximum effective concentration or EC50 values of different drugs. A lower EC50 value indicates higher potency of the drug. In the dose–response curve of two antihypertensive drugs, candesartan and irbesartan, a significant difference is observed in their EC50 values. A lower EC50 value for candesartan indicates that it is more potent than irbesartan, as it...
4.4K
Depolarizing Blockers: Pharmocokinetics
319
Depolarizing blockers are administered through intravenous injection. Succinylcholine is the most common choice of depolarizing blockers in emergency clinical practices. Although they have a rapid onset, they readily diffuse away from the motor end plate into the extracellular fluid. They are metabolized by enzymes such as liver butyrylcholinesterase and plasma pseudocholinesterases. This produces a short duration of action, typically 5-10 minutes long, unlike nondepolarizing blockers, which...
319
Factors Influencing Drug Absorption: Pharmaceutical Parameters
129
Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
129
Hepatic Drug Excretion: Enterohepatic Cycling
1.5K
Enterohepatic cycling involves the active secretion of drugs and their metabolites into the bile via transporters in the canalicular membrane of hepatocytes. This secretion is an integral part of the digestive process, releasing these substances into the gastrointestinal (GI) tract.
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
1.5K
Antihypertensive Drugs: Angiotensin II Receptor Blockers
714
In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
714


