Pharmacological evaluation of Rhazya stricta root extract / Evaluación farmacológica del extracto de raíz de Rhazya stricta

The present study aimed to screen the Rhazya stricta Decne root for its antihyperglycemic and antioxidants potential through invitro assays along with phytochemical and elemental analyses. The crude extract was prepared through maceration and fractionated using solvent-solvent extraction technique. The spectroscopic studies indicated the presence of various phytochemical classes in the extract and its fractions. The antioxidant assays showed notable results along with a good concentration of phenolic and flavonoid contents. Enzyme inhibition assays demonstrated glucose-lowering effects by inhibiting the enzyme activity which could reduce post-prandial blood glucose level. The Dipeptidyl peptidase-IV (DPP-IV) inhibition assay results showed the novel DPP-IV inhibition activity of the plant extract and all fractions showed noteworthy enzyme inhibition and antihyperglycemic activity. Conclusively, the Rhazya stricta root extract displayed its antioxidant and antihyperglycemic potential due to the presence of various classes of phytochemicals and micro-nutrients.

El presente estudio tuvo como objetivo examinar la raíz de Rhazya stricta Decne por su potencial antihiperglicémico y antioxidante a través de ensayos in vitro junto con análisis fitoquímicos y elementales. El extracto crudo se preparó por maceración y se fraccionó usando una técnica de extracción solvente-solvente. Los estudios espectroscópicos indicaron la presencia de varias clases fitoquímicas en el extracto y sus fracciones. Los ensayos antioxidantes mostraron resultados notables junto con una importante concentración de contenido fenólico y flavonoide. Los ensayos de inhibición enzimática demostraron efectos reductores de la glucosa al inhibir la actividad enzimática que podría reducir el nivel de glucosa posprandial en sangre. Los resultados del ensayo de inhibición de Dipeptidyl peptidase-IV (DPP-IV) mostraron la nueva actividad de inhibición de DPP-IV del extracto de la planta y todas las fracciones mostraron una notable inhibición enzimática y actividad antihiperglicémica. En conclusión, el extracto de raíz de Rhazya stricta Decne mostró su potencial antioxidante y antihiperglicémico debido a la presencia de varias clases de fitoquímicos y micronutrientes.

Isolation and identification of unknown impurities of alogliptin benzoate / 中国药科大学学报

@#By silica gel column chromatography, solvent extraction and preparative high performance liquid chromatography (HPLC), four new related substance were isolated and purified from the mass production and preparation process of alogliptin benzoate. Then it was analyzed and confirmed by various spectrum identification methods such as nuclear magnetic resonance (NMR) spectroscopy, high-resolution mass spectrometry (HR-MS) and Fourier-transform infrared spectroscopy (FTIR) according to its physical and chemical properties. The chemical structures of the four related substances produced in each step of the synthesis process of alogliptin benzoate were determined, and they were named as impurities L, M, T, and V. These four related substances were new impurities which were found for the first time. The isolation and identification of these impurities are of great importance to the quality control of alogliptin benzoate, and the optimization of manufacturing process.

Efficacy of saxagliptin in failed glycemic control of patients with type 2 diabetes mellitus / 中国生化药物杂志

Objective To explore the efficacy of saxagliptin in the treatment of failed glycemic control of patients with type 2 diabetes mellitus on the basis of established treatments.Methods 172 cases of failed glycemic control of patients with type 2 diabetes mellitus from June 2013 to December 2014 in department of endocrinology of the first hospital of Ningbo were selected and received health education of 8 weeks, then received saxagliptin on the basis of established treatments for a consecutive treatment of 12 weeks.The HbA1c, fasting blood glucose ( FBG), 2-hours postprandial blood glucose (2hPBG), body mass index (BMI), insulin dosage and adverse event were observed.Results The FBG,HbA1c and 2hPBG after treatment of 12 weeks were significantly lower than those pre-treatment[(7.1 ±2.0)vs.(8.3 ±1.6)mmol/L,(10.2 ±2.3)vs.(15.2 ±2.9)mmol/L,(7.0 ±1.5) vs.(8.0 ±1.7)%], with significant difference (all P <0.05), while there was no significant difference in BMI between pre-and post-treatment [(24.4 ±3.0)vs.(24.9 ±2.7)kg/m2].The insulin dose after treatment of 12 weeks was significantly lower than that pre-treatment[(22.6 ±7.9)vs. (32.3 ±8.2) U/d], with significant difference (P <0.05).There were two patients dropout because of the intolerable digestive tract symptom. Conclusion The adding of saxagliptin could control FBG,2hPBG and HbA1c effectively and decrease insulin dose, without gaining weight in the treatment of failed glycemic control of patients with type 2 diabetes mellitus on the basis of established treatments.

Synthesis of saxagliptin intermediate N-BOC-3-hydroxyadamantylglycine / 中国药学杂志

OBJECTIVE: To explore a new synthesis method of the saxagliptin intermediate of the dipeptidyl peptidase IV (DPP-IV)inhibitor saxagliptin, N-BOC-3-hydroxy-1-adamantylglycine, to reduce the synthesis cost of saxagliptin. METHODS: The synthesis used 1-adamantane carboxylic acid (1) as the starting material. Through achlorination, substitution, and decarboxylation afford 1-adamantyl methyl ketone (2) was obtained, which was then converted into 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid (3)by oxidation with potassium permanganate in aqueous NaOH. Compound 3 reacted with hydroxylamine hydrochloride to give the 2-(3-hydrox-1-adamantyl)-2-hydroxyimino acetic acid(4), and then oxime 4 was reduced, and got the amino with BOC2O to afford dipeptidyl peptidase IV (DPP-IV)inhibitor saxagliptin intermediate N-BOC-3-hydroxyadamanty- lglycine(5). RESULTS: We got a new compound 4 which had not been reported. The 36% overall yield was reached. CONCLUSION: This synthetic route is simple, its reaction conditions are mild, and the raw materials are cheap and readily available, so it is suitable for manufacturing purposes.

New and emerging drugs in type 2 diabetes / 대한내과학회지

Recent advances in understanding insulin secretion, action and signaling have led to the development of new pharmacological agents. Several new emerging drugs and drug classes for the management of diabetes are under development, including the incretin mimetic agents (exenatide, dipeptidyl peptidase 4 inhibitors, and glucagon-like peptide 1 analogues), the amylin analogue pramlintide, the cannabinoid-1 receptor antagonist rimonabant, the mixed peroxisome proliferator-activated receptor agonists muraglitazar and the inhaled insulin preparation Exubera. New drugs and technologic advances being made available will help achieve the goals of treating patients with diabetes to all the appropriate metabolic targets. Longer term studies will help providers weigh the benefits, adverse effects, cost, and unknown long-term risks of these medications.