Pharmazie最新文献

Zinc is an essential microelement, and its deficit causes various diseases and symptoms. In adults, especially in elderly individuals, zinc shortage can cause symptoms such as taste disorder, dermatitis, and susceptibility to infection. In children, zinc deficiency can lead to growth retardation. In 2017, the indication for zinc acetate dihydrate (NOBELZIN^®) was expanded from Wilson's disease to include hypozincemia, leading to wider use of zinc acetate dihydrate. At five years after this broadening of use, we conducted a post-marketing study (PMS) to investigate the utilization, safety, and effectiveness of zinc acetate dihydrate. Over 52 weeks, the overall incidence of adverse drug reactions (ADRs) was 9.4% (87/928). The most common ADR was copper deficiency (2.4%), followed by nausea (1.4%). Among 928 patients, 19 (2%) developed serious ADRs. Of the patients with copper deficiency, 92% were >65 years of age, and all had comorbidities at baseline. Physicians evaluated the effectiveness of zinc acetate dihydrate using three categories: "effective", "not effective", and "indeterminate". The overall efficacy rate was 83.0%. The average serum zinc levels were elevated from 50-60 μg/dL to >90 μg/dL within 12 weeks, and were maintained up to 52 weeks after administration. Among the symptomatic sub-categories, the efficacy rate was highest in pressure ulcer (96.2%; 25/26), followed by in stomatitis (87.5%; 42/48), and taste disorder (87.4%; 181/207). Among pediatric patients with developmental symptoms, an efficacy rate of 66% was achieved. In conclusion, zinc acetate dihydrate has been safely used, and has produced beneficial effects on various diseases and symptoms.

New anti- Toxoplasma gondii agents are in demand due to the emergence of high toxicity. Ginseng polysaccharides and saponins can be used to treat the replication of Toxoplasma gondii in an attempt to determine whether the medicinal uses of ginseng are supported by pharmacological effects. Anti- Toxoplasma gondii activities of ginseng polysaccharides and saponins were examined in vitro and in vivo. The findings are the survival time and rate of Toxoplasma gondii infected mice after the intake of the total polysaccharides and saponins increased compared to untreated control mice. The survival rate of mice treated with ginseng saponins was the highest at 83.3%, the phenomenon of splenomegaly of mice was decreased especially ( p < 0.05) treated with ginseng polysaccharides. Accordingly, ginseng polysaccharides and saponins have a potential application in anti-Toxoplasma gondii treatments.

The global pandemic of COVID-19 disease is caused by the pathogenic factor called SARS-CoV-2. Meanwhile, a series of vaccines and small-molecule drugs, including the mRNA vaccines and Paxlovid^®, have been approved, but their efficacy is decreased significantly due to the constant emergence of mutant viral strains. The R&D of host-directed therapeutics has great potential to overcome such limitations and provide new prevention and therapy options for patients with COVID-19 or high-risk group for SARS-CoV-2 infections. Transmembrane serine protease 2 (TMPRSS2) is belonging to a protein family with highly conserved serine protease domain whose crucial role in viral entry is to activate the spike protein of viruses to induce the fusion between host cells and viruses. In this review, we sketch the critical position of TMPRSS2 in the SARS-CoV-2 viral entry and summarize the advanced research and development of TMPRSS2 inhibitors, including repurposed drugs, as a new way to fight COVID-19.

Objective: Magnesium oxide is widely used for treating opioid-induced constipation, a serious analgesic-associated problem. Opioid analgesic users are often prescribed non-steroidal anti-inflammatory drugs, which are sometimes combined with acid suppressants to prevent gastrointestinal adverse events. Magnesium preparations combined with acid suppressants may diminish magnesium preparations' laxative effect. This study was aimed at evaluating the effect of magnesium preparations combined with acid suppressants on the incidence of opioid-induced constipation by using the Food and Drug Administration Adverse Event Reporting System. Methods: Adverse events were defined per the Medical Dictionary for Regulatory Activities; the term 'constipation (preferred term code: 10010774)' was used for analysis. After adjusting for patient background factors using propensity score matching, acid suppressants' effect on constipation incidence was evaluated in opioid users prescribed magnesium preparations alone as laxatives by using a test for independence. Key Findings: The Food and Drug Administration Adverse Event Reporting System contains 14,475,614 reports for January 2004 to December 2021. Significantly increased constipation incidence was related to magnesium preparations combined with acid suppressants, especially proton pump inhibitors (P < 0.0001, McNemar's test). Conclusion: Magnesium preparations combined with acid suppressants may diminish magnesium preparations' laxative effect; healthcare professionals should pay attention to this issue.

In patients with type 2 diabetes mellitus (T2DM), controlling serum uric acid (SUA) and blood glucose levels is important. Moreover, sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease SUA levels by accelerating urinary uric acid excretion. We investigated the effect of baseline urinary glucose levels on the relationship between SGLT2 inhibitors and SUA levels. We conducted a retrospective observational study using the electronic medical records of patients with T2DM of Kindai University Nara Hospital (April 2013 to March 2022). We divided the patients into two groups according to their baseline urinary glucose levels: the N-UG group, which included patients with negative urinary glucose strip test results (-), and the P-UG group, which included patients with positive urinary glucose strip test results (± or more). The changes in SUA levels before and after SGLT2 inhibitor administration were investigated. For comparison, the changes in SUA levels before and after the prescription of antidiabetic agents, excluding SGLT2 inhibitors, were also investigated. Our results revealed that SGLT2 inhibitors significantly decreased the SUA levels in patients in the N-UG group but tended to decrease its levels in those in the P-UG group. Regardless of the urinary glucose status at baseline, the administration of SGLT2 inhibitors may be useful for patients with T2DM to prevent the complications of hyperuricemia.

Immunoglobulin replacement therapy (IgRT) has advanced over the years and is used to treat many patients with primary immunodeficiencies reducing the number of infections and the burden of disease. We investigated the perception of IgRT in two patient groups (UKPIPS and PID UK) and their condition through a short survey. The survey was a multiple-choice short survey consisting of 20 questions completed either online or on paper. Data analysis was performed using SAS analysis software using regression analysis, correlation analysis and t-tests. Statistical significance was considered with p<0.05. 278 surveys were analysed which showed that the majority of participants were satisfied with the immunoglobulin therapy they received (n=225, 80.9%). However, there was a small but significant number of participants (n=19, 6.9%) that still experienced severe and very severe infections despite adequate IgRT. 236 (84.9%) participants reported limitations in daily life due to infections. The dissatisfied participants (n=55, 18.3%) had more non-routine visits to healthcare providers, higher numbers of antibiotic treatments and more days absent from school, work, university or equivalent than the satisfied participants.

Bisphosphonate (BPN) therapy, which mainly targets osteoporosis, evolves rapidly, leaving patients and physicians with a substantial collection of BPN regimen options. In this study, we aimed to clarify BPN medication adherence between weekly and monthly regimens using a nationwide claims database in Japan. We analyzed 5,016 patients with a screening period of 3 months and a 12 month observation period who started using BPN. We used propensity score matching with baseline patient background after dividing the patients into two groups: weekly and monthly BPN users. Medication adherence was calculated using proportion days cover (PDC). A PDC of > 80% was 55.9% and 52.5% in monthly and weekly formulas, respectively, during the 12 months after initiating BPN treatment. PDC-based BPN medication adherence was higher in monthly regimens than in weekly regimens (66.3±34.0 vs. 64.1±36.8%). No differences were found in the proportion of patients with > 80% medication adherence between the monthly and weekly regimens after stratifying patient background using propensity score matching. Our clinical findings highlight the importance of closely monitoring BPN medication adherence, particularly during the initial year of therapy. Notably, half of the patients with osteoporosis exhibited low medication adherence. Therefore, prioritizing monthly regimens over weekly regimens is crucial to promote BPN adherence and ensure optimal treatment outcomes.

Endoplasmic reticulum stress (ER stress) is suggested to promote cardiomyocyte apoptosis and ultimately lead to ischemic injury. Inhibition of ER stress-induced apoptosis may be a therapeutic strategy for MI injury. Astragaloside-IV (AST) from Astragalus membranaceus (Fisch) Bge, was reported to have cardioprotective properties. In this study, we investigated the protective effect of AST on cardiomyocytes against hypoxia injury by regulating ER stress and inhibiting apoptosis. H9c2 cardiomyocytes were divided into three groups, normal group, hypoxia group and AST group. Cell viability was determined by CCK-8 assay. Intracellular reactive oxygen species (ROS) production was detected by DCFH-DA (2,7- dichloro-dihydrofluorescein diacetate) florescent staining. The study showed that AST treatment could significantly increase the cell viability of H9c2 cells exposed to hypoxia. Furthermore, AST could restrain cell apoptosis and decrease the production of ROS. Compared with normal group, the protein levels of Bax, caspase-3, caspase-9, GRP78, p-eIF2α, and CHOP were enhanced in the hypoxia group, whereas the protein level of Bcl-2 was dramatically reduced. Compared with hypoxia group, AST markedly inhibited the phosphorylation of eIF2α and the expression of caspase-3, caspase-9 and CHOP, and promoted the protein expression of Bcl-2. Thus, AST can inhibit the ER stress-mediated apoptosis, partly through the eIF2α/CHOP pathway suppression to inhibit ER stress.

The antitumor drug candidate X-05 is being developed as an innovative anti-lung cancer drug candidate due to its excellent antitumour activity. A Caco-2 cell permeability study and solubility study confirmed that X-05 belonged to BCS class or compounds. Therefore, the main challenge is to develop appropriate preparations for preclinical studies and further clinical phase research. By evaluating the preliminary results of kinetic solubility in biorelevant media and the structural analysis of X-05 and polymers, three polymers PVP K30, PVP VA 64 and HPMCAS, which may have intermolecular interactions with X-05, were chosen to select the optimal carrier for X-05 to prepare amorphous solid dispersions (ASDs). ASD X-05-PVP VA 64 was selected as the optimal polymer by evaluating its kinetic solubility in biorelevant media and solid stability. The physical and chemical properties of ASD X-05-PVP VA 64 remain stable when the drug loading is as high as 50%. The drug-polymer interactions of ASD X-05-PVP VA 64 were studied by ultraviolet spectrophotometry, nuclear magnetic resonance spectrometry, infrared and Raman spectrophotometry, and the results indicated that the intermolecular hydrogen bond interaction between the drug and polymer was the foundation of the solubilization and stabilization of X-05 in PVP VA 64.

Free amino acids constitute the largest portion (40%) of the natural moisturizing factor. Their level might decline and cause dry skin condition. The treatment strategy involves the replenishment of these components to the skin, and, to our knowledge, there are no reports that involve dermal delivery of free amino acids. The purpose of the current study was therefore to prepare and characterize different micro-emulsions, micro-emulsion-based hydrogels, and hydrophilic creams loaded with free amino acids for dermal delivery. Oil-in-water microemulsions were prepared using carefully selected formulation components. Poloxamer^® 407 and carbopol^® 934 were used to prepare the hydrogels. All the formulations were characterized for physico-chemical, permeation and cytotoxicity properties. The results showed that the prepared microemulsions had desired droplet size, size distribution, zeta potential, refractive index, and pH. In the gel preparations, the elastic properties prevailed over the viscous behavior. The hydrogels had non-Newtonian shear-thinning behavior with some thixotropic properties. The free amino acids permeated into the deeper layers of the stratum corneum from the microemulsions, and microemulsion-based hydrogels as compared to conventional hydrophilic cream. The hydrogels were more effective than the microemulsions to deliver the FAAs to the desired site of the skin in a sustained manner. Poloxamer-based hydrogel permeated into deeper skin layers than Carbopol-based hydrogel. Formulations prepared using standard free amino acids and those extracted and purified from oyster mushroom had similar characteristics. All the formulations were stable and safe to be applied topically. In conclusion, microemulsions and microemulsion-based hydrogels can be considered as safe carrier systems for dermal delivery of free amino acids.