-
The Journal of Sexual Medicine Jun 2024
Topics: Humans; Testosterone; Male; Fertility Preservation; Hormone Replacement Therapy
PubMed: 38945687
DOI: 10.1093/jsxmed/qdae046 -
Journal of Thrombosis and Haemostasis :... Jul 2024
Topics: Humans; Vitamin K; Perioperative Care; Anticoagulants; Blood Coagulation
PubMed: 38945667
DOI: 10.1016/j.jtha.2024.04.012 -
Annales Pharmaceutiques Francaises Jun 2024Nanosuspensions have emerged as a promising avenue in pharmaceutical innovation, particularly for enhancing the bioavailability of poorly soluble medications. This... (Review)
Review
INTRODUCTION
Nanosuspensions have emerged as a promising avenue in pharmaceutical innovation, particularly for enhancing the bioavailability of poorly soluble medications. This article explores the transformative potential of nanosuspensions, emphasizing the critical role of particle size reduction through nanonization techniques. With conventional approaches often falling short in addressing the bioavailability challenges of hydrophobic drugs, nanosuspensions offer multifaceted applications and distinctive advantages in drug delivery.
METHODS
The study delves into various nanosuspension preparation techniques, including high-pressure homogenization, media milling, emulsification-solvent evaporation, precipitation, and supercritical fluid processes. Each method brings unique advantages and limitations, contributing to the expanding repertoire of nanosuspension formulation methods. The article emphasizes the necessity for meticulous planning, evaluation, and ongoing research across different drugs to optimize their use effectively.
RESULTS
Nanosuspensions exhibit versatility in administration routes, spanning parenteral, peroral, ocular, and pulmonary pathways, making them applicable across diverse dosage forms. Current efforts are directed towards furthering their application in site-specific medication administration, indicating their potential in tailored therapeutic strategies. Nanosuspensions offer a promising solution for enhancing drug solubility and bioavailability, addressing the persistent challenge of poor solubility in pharmaceutical compounds.
DISCUSSION
The significance of careful formulation and stabilization using polymers and surfactants is underscored, ensuring the efficacy and safety of nanosuspensions. By discussing the benefits, drawbacks, and nuances of each preparation technique, the article aims to simplify future research endeavors in the field of nanosuspensions. Additionally, a comprehensive overview of nanosuspensions, including their preparation methods, benefits, characterization, patents, marketed products, and intended uses, sheds light on this evolving domain in pharmaceutical sciences.
CONCLUSION
Nanosuspensions represent a promising approach for overcoming bioavailability challenges associated with poorly soluble medications. The article highlights their transformative potential in pharmaceutical innovation, emphasizing the importance of continued research and optimization to harness their benefits effectively. Nanosuspensions offer a viable solution for enhancing drug solubility and bioavailability, with implications for improving therapeutic outcomes in various medical conditions.
PubMed: 38945393
DOI: 10.1016/j.pharma.2024.06.003 -
Annales Pharmaceutiques Francaises Jun 2024The present work represents a reverse-phase high-performance liquid chromatography method in addition to stability studies for sequential estimation of Remogliflozin...
OBJECTIVE
The present work represents a reverse-phase high-performance liquid chromatography method in addition to stability studies for sequential estimation of Remogliflozin Etabonate, Vildagliptin, and Metformin HCl in tablet formulation.
METHOD
The mentioned method utilizes a Phenomenex Luna C18 column (250 × 4.6 mm, 5 μm). It consists of a column oven's temperature of 35 ͦ C. Mobile phase includes a mixture of 50% Phosphate buffer (pH - 6.8) and 50% Acetonitrile along with a flow rate of 0.8 mL/min and 20 minutes of run time. The injection volume was 20 μL. 217 nm is a detection wavelength, and a PDA detector is used for detection.
RESULTS
The suggested technique was proven and validated per the ICH Q2(R1) guideline. The combination was put under stress conditions that included acid, base, thermal, photolytic, and oxidative degradation. The combination was considerably degraded under oxidative, acidic, and basic circumstances for deterioration, and the degradation results were accurately identified from the observed peaks, demonstrating the method's effectiveness in detecting stability.
CONCLUSION
The technique was quick, precise, sensitive, and accurate; as a result, it may be used in quality control laboratories and the pharmaceutical industry for routine quality monitoring of tablets containing all three medications.
PubMed: 38945392
DOI: 10.1016/j.pharma.2024.06.006 -
International Journal of Antimicrobial... Jun 2024Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore...
PURPOSE
Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore potential factors to influence its effectiveness and safety.
METHODS
A Model-Based Meta-Analysis (MBMA) of 96 articles was conducted, focusing on factors like dosage, bacterial species, and combined antibiotic therapy. The analysis evaluated mortality rates and incidence rate of renal dysfunction, also employing parametric survival models to assess 30-day survival rates.
RESULTS
In the study involving 96 articles and 9,716 patients, polymyxin B's daily dose showed minimal effect on overall mortality, with high-dose group mortality at 33.57% (95% CI: 29.15-38.00) compared to the low-dose group at 35.44% (95% CI: 28.99-41.88), p=0.64. Mortality significantly varied by bacterial species, with Pseudomonas aeruginosa infections at 58.50% (95% CI: 55.42-63.58). Monotherapy exhibited the highest mortality at 40.25% (95% CI: 34.75-45.76), p<0.01. Renal dysfunction was more common in high-dose patients at 29.75% (95% CI: 28.52-30.98), with no significant difference across antibiotic regimens, p=0.54. The 30-day Overall Survival rate for monotherapy therapy was 63.6% (95% CI: 59.3-67.5) and 70.2% (95% CI: 64.4-76.2) for association therapy with β-lactam drugs.
CONCLUSIONS
The dosage of Polymyxin B doesn't significantly change death rates, but its effectiveness varies based on the bacterial infection. Certain bacteria like Pseudomonas aeruginosa are associated with higher mortality. Combining Polymyxin B with other antibiotics, especially β-lactam drugs, improves survival rates. Side effects depend on the dose, with lower doses being safer. These findings emphasize the importance of customizing treatment to balance effectiveness and safety.
PubMed: 38945178
DOI: 10.1016/j.ijantimicag.2024.107262 -
Ultrasonics Sonochemistry Jun 2024The study aimed to extract and encapsulate betalain pigment from prickly pear (Opuntia ficus-indica) using ultrasound-assisted extraction and eco-friendly glycerol....
The study aimed to extract and encapsulate betalain pigment from prickly pear (Opuntia ficus-indica) using ultrasound-assisted extraction and eco-friendly glycerol. Subsequent analysis encompassed assessing its thermal stability, shelf-life, bio-accessibility, and biological properties. The process optimization employed Response Surface Methodology (RSM), focusing on glycerol concentration (20-50 %), sample to solvent ratio (1:10-1:20), temperature (30-60 °C), and time (10-30 min). Optimal conditions were determined as 23.15 % glycerol, 1:10 sample to solvent ratio, 10.43 min treatment time, and 31.15 °C temperature. Under these conditions, betalain content reached 858.28 mg/L with a 93.76 % encapsulation efficiency. Thermal stability tests (80-180 °C; 30 & 60 min) showed degradation of betalain with higher temperatures and longer durations, affecting the visual aspect (ΔE) of the pigment. Encapsulated betalain exhibited favorable shelf stability, with optimal storage life of 404.27 days at 4 °C in amber conditions, compared to 271.99 days at 4 °C without amber, 141.92 days at 25 °C without amber, and 134.22 days at 25 °C with amber. Bio-accessibility of encapsulated betalain was significantly higher (2.05 ± 0.03 %) than conventionally extracted pigment (1.03 ± 0.09 %). The encapsulated pigment displayed strong anti-inflammatory properties in dosages of 2-20 µL, with no cytotoxic effects. Additionally, incorporation into gummies was successful and visually approved by sensory panellists. Glycerol proved to be a green encapsulating agent for betalain, offering high shelf life and bio-accessibility, making it suitable for food industry applications. The encapsulated pigment demonstrated robust thermal stability and shelf life, making it suitable for food industry applications. This study highlights glycerol's potential as a sustainable alternative for natural pigment extraction.
PubMed: 38945052
DOI: 10.1016/j.ultsonch.2024.106975 -
Nihon Yakurigaku Zasshi. Folia... 2024Inclisiran sodium (Brand name: LEQVIO for s.c. injection syringe 300 mg, hereinafter referred to as inclisiran), a small interfering ribonucleic acid (siRNA)...
Inclisiran sodium (Brand name: LEQVIO for s.c. injection syringe 300 mg, hereinafter referred to as inclisiran), a small interfering ribonucleic acid (siRNA) product that targets the mRNA that encodes the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein was approved on September 25, 2023 for the indication of "Familial hypercholesterolemia, hypercholesterolemia" in Japan. Inclisiran is conjugated on the sense strand with triantennary N-acetylgalactosamine to facilitate uptake by hepatocytes. In vitro and in vivo pharmacology studies demonstrated the lowering effects of PCSK9 and LDL-C in hepatocytes and cynomolgus monkeys. It was considered unlikely to cause clinically significant risks due to toxicities arising from complementary binding to non-target RNA sequences (hybridization-dependent off-target effects). Clinical trials conducted globally including Japan in patients with familial hypercholesterolemia and hypercholesterolemia who did not reach the LDL-C target showed that inclisiran sodium 300 mg dosed at Day 1, Day 90 and then every 6 months demonstrated significant LDL-C reduction and the efficacy sustained long. The majority of patients achieved the guideline recommended LDL-C targets. Inclisiran sodium 300 mg was well tolerated and there were no specific safety concerns. Therefore, inclisiran is expected to be a new therapeutic option for the patients with familial hypercholesterolemia and hypercholesterolemia.
Topics: Humans; Cholesterol, LDL; Animals; RNA, Small Interfering; Proprotein Convertase 9; Hypercholesterolemia; Hyperlipoproteinemia Type II
PubMed: 38945909
DOI: 10.1254/fpj.24018 -
Nihon Yakurigaku Zasshi. Folia... 2024Pertuzumab and trastuzumab are anti-HER2 humanized monoclonal antibodies with different mechanisms of action. Their combination is expected to suppress intracellular... (Review)
Review
[Pharmacological properties and clinical development overview of pertuzumab (genetical recombination), trastuzumab (genetical recombination) and vorhyaluronidase alfa (genetical recombination) (PHESGO combination for subcutaneous injection MA, IN)].
Pertuzumab and trastuzumab are anti-HER2 humanized monoclonal antibodies with different mechanisms of action. Their combination is expected to suppress intracellular HER2 signaling additively or synergistically. Their combination is widely recommended worldwide and has been established as a standard of care for HER2-positive breast cancer. However, improvement is required because of the prolonged time of intravenous infusion. Vorhyaluronidase alfa (rHuPH20) depolymerizes hyaluronan in the subcutaneous connective tissue. It's reported to increase the permeability and absorption levels of drugs. PHESGO combination for subcutaneous injection MA/IN (PHESGO) is a fixed-dose combination of pertuzumab, trastuzumab, and rHuPH20. A confirmatory phase III study (FeDeriCa) was conducted following a dose-finding phase I study (BO30185). Patients with HER2-positive early breast cancer were randomly assigned to receive either intravenous infusion of pertuzumab and trastuzumab or subcutaneous injection of PHESGO, in combination with chemotherapy, to compare the pharmacokinetics (PK), efficacy and safety. A phase II study (PHranceSCa) was also conducted to assess patients' preference and satisfaction. Based on these results, population PK analysis, and other data, PHESGO obtained marketing approval in Japan in September 2023 with indications for "HER2-positive breast cancer" and "advanced or recurrent HER2-positive colorectal cancer that has progressed following cancer chemotherapy and is not amenable to curative resection". By reducing the administration time, PHESGO is expected to contribute to various needs of patients and improvement of their daily lives. Since drug preparation is not required, it can provide convenience to healthcare professionals, leading to stress reduction of medical resources as well.
Topics: Humans; Trastuzumab; Antibodies, Monoclonal, Humanized; Hyaluronoglucosaminidase; Injections, Subcutaneous; Breast Neoplasms; Drug Combinations; Clinical Trials as Topic; Receptor, ErbB-2; Female; Recombinant Proteins; Cell Adhesion Molecules
PubMed: 38945908
DOI: 10.1254/fpj.24022 -
Journal of Nutritional Science and... 2024Excessive immune response and inflammation are associated with an increased risk of various diseases. In particular, excessive myeloperoxidase (MPO) activity in... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Excessive immune response and inflammation are associated with an increased risk of various diseases. In particular, excessive myeloperoxidase (MPO) activity in neutrophils causes inflammatory reactions and lifestyle-related diseases. Adlay has a long history of being used as a traditional Chinese medicine. Polyphenols present in adlay seeds are expected to have the effect of suppressing excessive immune and inflammatory responses. Here, we conducted a randomized, double-blind, parallel group, placebo-controlled study was conducted to evaluate the suppressing effects of adlay seeds extract on excessive immune responses. One hundred and twenty adults participated in the study and they were equally divided into an adlay tea intake group and a placebo group. MPO activity was significantly elevated in the placebo group after 8-wk ingestion, while no significant change was observed in the adlay group. Vascular endothelial functions improved in the adlay group, especially in subjects over 40 y old. These results indicate that adlay tea intake may suppress an excessive immune and inflammatory responses, and improve arterial stiffness. Since caffeic acid, p-coumaric acid, and ferulic acid detected in adlay tea are known to inhibit MPO activity, these polyphenols may be the major functional molecules. Collectively, adlay tea is considered to have a preventative effect against lifestyle-related diseases through improving vascular endothelial function by effects to maintain immune homeostasis of the contained polyphenols. This trial was registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000032263).
Topics: Humans; Double-Blind Method; Male; Female; Adult; Tea; Homeostasis; Middle Aged; Endothelium, Vascular; Polyphenols; Peroxidase; Seeds; Plant Extracts; Inflammation; Caffeic Acids; Medicine, Chinese Traditional
PubMed: 38945894
DOI: 10.3177/jnsv.70.280 -
Journal of Nutritional Science and... 2024The purpose of this study was to examine whether 4 wk of daily ingestion of milk fat globule membrane (MFGM) combined with exercise training improves physical... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of Milk Fat Globule Membrane Supplementation Following Exercise Training on Physical Performance in Healthy Young Adults: A Randomized Double-Blind, Placebo-Controlled Pilot Trial.
The purpose of this study was to examine whether 4 wk of daily ingestion of milk fat globule membrane (MFGM) combined with exercise training improves physical performance-muscle strength, agility and muscle power-in healthy young adults. The study was designed as a randomized, double-blind, and placebo-controlled trial. Twenty healthy young adults received either an MFGM powder containing 1.6 g of fat and 160 mg of sphingomyelin or an isocaloric placebo powder daily throughout 4 wk of power or agility training. Physical performance tests and body composition measurements were conducted before and after the 4-wk intervention. Ingestion of MFGM did not affect isometric or isokinetic muscle strength, but it was associated with a greater increase in vertical jump peak power compared with placebo. There were no significant changes in body weight or lean body mass during the intervention period in either group, and no significant differences between groups. We conclude that daily MFGM supplementation combined with exercise training has the potential to improve physical performance in young adults; however, further studies with larger sample sizes should be conducted to obtain more evidence supporting achievement of improved physical performance through MFGM supplementation.
Topics: Humans; Double-Blind Method; Glycolipids; Lipid Droplets; Glycoproteins; Male; Young Adult; Female; Dietary Supplements; Muscle Strength; Body Composition; Exercise; Pilot Projects; Adult; Physical Functional Performance; Body Weight; Sphingomyelins; Muscle, Skeletal
PubMed: 38945893
DOI: 10.3177/jnsv.70.273