Wrinkle-Improving Effect of Novel Peptide That Binds to Nicotinic Acetylcholine Receptor.

Wrinkles, one of the most common signs of aging, are primarily caused by the continuous contraction of muscles. Muscle contraction is induced by the binding of acetylcholine (ACh), released at the neuromuscular junction, to nicotinic acetylcholine receptor (nAChR) present on the muscle cell surface. In this study, we aimed to develop a wrinkle-improving peptide that inhibits the binding of ACh to nAChR using peptide phage display technology. Our peptide showed a remarkably high binding affinity to nAChR subunit α1, with a value below 1 µM, and was found to inhibit the action of ACh through its interaction with these receptors. Furthermore, it increased collagen synthesis in skin cells and upregulated the expression of the aquaporin-3 (AQP3) and hyaluronan synthase-2 (HAS2) genes. These results confirm that the peptide effectively inhibits muscle contraction and enhances skin elasticity and hydration, contributing to its wrinkle-reducing effects. Clinical studies on humans observed significant improvement in wrinkles after three weeks of use, with substantial reduction observed after six weeks. In conclusion, these findings demonstrate the efficacy of the peptide (named Medipep) in reducing wrinkles.

A randomized, open-label, crossover study to compare the safety and pharmacokinetics of two tablet formulations of tenofovir (tenofovir disoproxil and tenofovir disoproxil fumarate) in healthy subjects.

PURPOSE: This study was performed to compare the pharmacokinetic properties and assess bioequivalence for the test formulation (HUG116 tablet; tenofovir disoproxil) and reference formulation (Viread tablet; tenofovir disoproxil fumarate). MATERIALS AND METHODS: A randomized, open-label, single-dosing, two-treatment, two-period, two-sequence cross-over study was conducted in 50 healthy subjects. All subjects were randomly assigned to one of the two sequences, and they received a single dose of test or reference formulation in the first period and the alternative formulation during the next period under fasting conditions. Serial blood samples for pharmacokinetic evaluation were collected up to 72 hours post dose, and the pharmacokinetic parameters were estimated by noncompartmental methods. Throughout the study, tolerability was assessed based on adverse events, vital signs, and clinical laboratory tests. RESULTS: The test formulation showed similar pharmacokinetic profiles to those of the reference formulation. The geometric mean ratio and 90% confidence interval (CI) of the test formulation to the reference formulation for maximum plasma concentration (Cmax) was 0.93 (0.87 - 0.99), and the corresponding value for the area under the concentration-time curve from time zero to time of last quantifiable concentration (AUCt) was 0.94 (0.89 - 0.99). Both CIs were within the conventional bioequivalence range of 0.8 - 1.25. The tolerability profile was not significantly different between the test and reference formulations. CONCLUSION: This study found that the PKs of the test formulation (HUG116 tablet; tenofovir disoproxil) and reference formulation (Viread tablet; tenofovir disoproxil fumarate) were similar, and the test formulation met the regulatory criteria for assuming bioequivalence with the reference formulation.

Bioequivalence for a Fixed-Dose Combination Formulation of Bazedoxifene and Cholecalciferol Compared With the Corresponding Single Entities Given Together.

A fixed-dose combination (FDC) formulation of bazedoxifene 20 mg and cholecalciferol 8 mg was developed to increase medication compliance and convenience for osteoporosis patients. This study was conducted to demonstrate bioequivalence by comparing the pharmacokinetic (PK) profiles and tolerability of an FDC tablet and the individual component tablets. A randomized, open-label, single-dosing, 2-treatment, 2-period, 2-sequence crossover study was conducted in 52 healthy subjects. All subjects were randomly assigned to 2 sequences, and they received FDC tablets of bazedoxifene and cholecalciferol and individual component tablets. Serial blood samples for PK evaluation were collected up to 24 hours predose and 120 hours postdose, and the PK parameters were estimated by noncompartmental methods. Throughout the study, tolerability was assessed based on adverse events, vital signs, and clinical laboratory tests. Of the enrolled 52 subjects, 47 subjects completed the study. The results, the geometric mean ratios (GMRs) and 90% confidence intervals (90%CIs), of bazedoxifene Cmax and AUC0-t for FDC to single entities given together were 0.98 (0.91-1.05) and 1.02 (0.97-1.07), respectively. The GMRs (90%CIs) of cholecalciferol Cmax and AUC0-t for FDC to single entities given together were 0.96 (0.91-1.00) and 0.94 (0.90-0.99), respectively. Overall, the GMRs (90%CIs) of the PK parameter of bazedoxifene and cholecalciferol fell within the conventional bioequivalence range of 0.8-1.25. There were no clinically significant differences in the safety profile between the 2 treatments. In conclusion, this study confirmed the development of a new FDC drug by demonstrating that the FDC formulation of bazedoxifene and cholecalciferol is biologically equivalent to the coadministered individual formulations.

Pseudoceramide-containing physiological lipid mixture reduces adverse effects of topical steroids.

PURPOSE: Various therapeutic approaches have been suggested for preventing or reducing the adverse effects of topical glucocorticoids, including skin barrier impairment. Previously, we have shown that impairment of skin barrier function by the highest potency topical glucocorticoid, clobetasol 17-propinate (CP), can be partially prevented by co-application of a physiological lipid mixture containing pseudoceramide, free fatty acids, and cholesterol (multi-lamellar emulsion [MLE]). Skin atrophic effects of CP were also partially reduced by MLE. In this study, the preventive effects of MLE on the lowest potency topical glucocorticoid, hydrocortisone (HC), were investigated using animal models. METHODS: Anti-inflammatory activity of topical HC was evaluated using a 12-O-tetradecanoylphobol-13-acetate-induced skin edema model. Topical steroid induced adverse effects were evaluated using hairless mouse. RESULTS: The results showed that the anti-inflammatory activity was not altered by co-application of either MLE or hydrobase. However, co-application of MLE and 1.0% HC showed less impairment in the epidermal permeability barrier function, skin hydration, and skin surface pH compared with hydrobase. Stratum corneum integrity, evaluated by measuring trans-epidermal water loss after repeated tape stripping, showed less damage with MLE co-application. Long-term application of topical HC induced skin atrophy, measured by a reduction in skinfold and epidermal thickness and in the number of epidermal proliferating cell nucleus antigen (PCNA)-positive keratinocytes. Co-application of MLE did not affect the skinfold or epidermal thickness, but the number of PCNA-positive keratinocytes was less decreased with MLE use. CONCLUSIONS: These results suggest that co-application of MLE is effective in reducing the local adverse effects of low-potency topical glucocorticoids and supports the therapeutic efficacy of physiological lipid mixtures on skin barrier function.

A Case of Retroperitoneal Castleman's Disease / 대한비뇨기과학회지

Castleman's disease (angiofollicular lymph node hyperplasia) is a large benign tumor. Most of the lesion are located in mediastinum, but some presents as an isolated retroperitoneal mass radiographically indistinguishable from retroperitoneal malignancy. We report a case of the hyaline-vascular variant of Castleman's disease presenting as a palpable abdominal mass.