No abstract

No abstract

No abstract

No abstract

Balaglitazone (DRF-2593) is a novel partial agonist of PPAR-gamma (γ), which is developed by Dr. Reddy's laboratories India. Balaglitazone is a second generation peroxisome proliferator-activated receptor (PPAR) gamma agonist with only partial agonistic properties. Balaglitazone is currently being evaluated in phase III clinical trial in United States and Europe. Selective PPAR-γ modulators bind in distinct manners to the ligand-binding pocket of PPAR-γ, leading to alternative receptor conformations, differential cofactor recruitment/displacement, differential gene expression, and ultimately differential biological responses. Based on this concept, new and improved novel antidiabetic agents are in current development. Clinical studies conducted with 409 subjects of randomized, double blind, parallel-group placebo and active comparator-controlled subject groups to determine the efficacy and safety of Balaglitazone. The study showed that the trial met its primary endpoint. Balaglitazone treated groups shown significantly reduce of HbA1c (%), FSG (mmol/L), postprandial glucose as comparison to pioglitazone. Phase III clinical studies data clearly shows that Balaglitazone provides robust glycemic control as an add-on to insulin therapy. Balaglitazone 10 mg and 20 mg show the similar magnitudes of the effects which comparable to the effects seen in the pioglitazone 45 mg group. The incidence of fluid retention and fat accumulation fewer than those observed with pioglitazone 45 mg. Hence, Balaglitazone is prominent candidate of new glitazone which requires fewer doses as comparison pioglitazone and shows better safety profile less incidence of special adverse effect like heart failure, peripheral oedema, and myocardial infarction. Unlike other marketed PPAR gamma agonists, Balaglitazone shows less fluid retention, less heart enlargement and no reduction of bone formation than full PPAR gamma agonists in preclinical studies. In present review, we have tried to cover classification PPARs various ligands, chemistry, physical properties, commercial synthesis, current patent status, polymorphic information, receptor interaction, pharmacophore rational, mechanism, adverse effect and clinical status of Balaglitazone, giving emphasis on medicinal chemistry aspect.

In our earlier study, we demonstrated hypoglycemic activity of camel milk in diabetic rats. In continuation of that study, a further study was planned to know whether raw camel milk, pasteurized camel milk and lectoferrin added camel milk have similar response or different response in chemically pancreatectomized rats. 32 Male albino rats were rendered diabetic by a single intra peritoneal injection of streptozotocin 50mg/kg body weight. Streptozotocin induced diabetic rats were randomized to receive either raw camel milk, pasteurized camel milk, raw camel milk + lactoferrin, or cattle milk and control [non diabetic rats (n=8)] which were followed for 4 weeks. Blood glucose levels of these rats were estimated at weekly interval for four consecutive weeks. Statistical significance was tested by ANOVA with post hoc comparison between group means.Initial mean blood glucose levels of different groups i.e. Gp.I, Gp.II, Gp.III, Gp.IV and Gp.V were 169.68±28.73, 135.44±20.91, 175.04±35.98, 168.38±18.67 and 85.94±9.37 mg/dl, respectively. After four weeks of trial, mean blood glucose levels of these groups were 81. 54±11.43, 113±29.09, 93.24±11.56, 203.79±40.66 and 77.28±7.41 mg/dl, respectively. There was significant difference with raw camel milk (mean difference 88.14±17.3, p<0.02), this difference is decreased after pasteurization (mean difference 22.4±8.18, p 0.5) and there was no added advantage after adding lactoferrin (mean difference 81.8±24.42, p<0.05).The present study indicates that there was significant decrease in mean blood sugar level in diabetic rats getting raw camel milk. There were no added advantages of adding lactoferrin in raw camel milk. Hypoglycemic activity of camel milk decreases after pasteurization. Camel milk may be a therapeutic adjunctive option for diabetes mellitus in humans.

A macromolecular pro-drug of a known anti-viral agent Zidovudine (AZT) was synthesized and evaluated as a sustained drug delivery system. The pro-drug was synthesized by coupling the drug to 2-hydroxyethyl methacrylate (HEMA) through a succinic spacer to get a monomeric drug conjugate which was polymerized to obtain the polymeric pro-drug. The pro-drug was subjected for in-vitro drug release study in buffers of pH 1.2 and 7.4. The hydrolytic stability of the pro-drug to pepsin was assessed in simulated gastric fluid (SGF, pH 1.2) and to α-chymotrypsin in simulated intestinal fluid (SIF, pH 7.4). The results showed that the drug release from the polymeric backbone takes place in a sustained manner over a period of 24 h, and the amount of drug released was comparatively higher at pH 7.4. Plasmatic hydrolysis studies of succinylzidovudine showed nearly complete release of AZT. At all pH conditions in the presence and absence of α-chymotrypsin, AZT was released preferentially in comparison with the succinyl derivative. The in-vivo release studies in rabbits after oral administration of AZT conjugate demonstrated a sustained release of parent drug over a period of 24 h. The pro-drug provided a significant increase in the area under the plasma concentration time curve as compared to free drug and extended the plasma half-life from 1.06 h to 8.08 h. This study suggested that, after oral administration, the drug-polymer conjugate can release AZT for prolonged periods, thus improving the pharmacokinetics of AZT and decreasing the fluctuation in plasma drug levels that can lead to toxicity.

Objectives Barleria cristata (Family: Acanthaceae), commonly known as Philippine violet, is used in different ethnomedical systems for the treatment of a wide range of ailments. This review aimed to provide a scientific overview of B. cristata with reference to its ethnobotanical aspects, geographical distribution, medicinal uses, phytochemistry and pharmacological activity, and critical analyses research gaps and future research opportunities for investigations on this plant. Key findings Ethnomedical uses of the plant have been observed in lungs disorders, inflammatory conditions, toothache, anaemia, snake bite, diabetes and tuberculosis. The exhaustive bibliographic research carried out on this plant revealed that the plant parts are rich in various phytochemical constituents including triterpenes, phenolic compounds, glycosides and flavonoids type phenolic compounds. Furthermore, the plant was also investigated in terms of its anti-inflammatory, antibacterial, antidiabetic, antifungal, hepatoprotective and antioxidant activity. Conclusions This review confirms that B. cristata is a potential herb for the treatment of a wide range of diseases especially lung disorders and inflammatory conditions. Modern pharmacological studies have also validated many ethnobotanical uses of B. cristata, though data regarding many aspects of this plant such as mechanism of action, adverse effects of extracts and active compounds are still limited which call for additional studies.