Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan最新文献

Introduction: This study examines current OTC pharmaceuticals in Japan categorized as potential substances for abuse and discusses future initiatives for drug abuse prevention.

Methods: The Pharmaceuticals and Medical Devices Agency package inserts search function was used to identify OTC pharmaceuticals containing substances prone to abuse. Subsequently, the corresponding OTC pharmaceuticals containing the designated ingredients were investigated, analyzing their therapeutic and risk categories.

Results: In total, 1427 (13.9%) OTC pharmaceuticals contained the designated ingredients, with those containing methylephedrine and dihydrocodeine accounting for the majority (1245/1427, 87.2%). Among the therapeutic categories, oral cold medicines were predominant at 564, followed by antitussives and expectorants at 213, and oral rhinitis medicines at 100. Regarding risk categories, designated schedule II pharmaceuticals predominated in 9 out of 11 therapeutic category classifications.

Conclusion: Designated schedule II pharmaceuticals, such as oral cold medicines, antitussives and expectorants, and oral rhinitis medicines, pose a high risk of drug abuse. Addressing this challenge necessitates collaboration between pharmacists and registered sales clerks to implement preventive measures aligned with current trends in drug abuse.

This review highlights the author's research conducted at Mukogawa Women's University from April 2002 to March 2024. The work is categorized into following three areas: (1) Evaluation of the bitterness of oral medications using a taste sensor, (2) Development of drug delivery systems utilizing poly(lactic-co-glycolic acid) (PLGA), and (3) Clinical pharmaceutical evaluation of various injectable formulations. In section (1), the bitterness of oral medications, both alone and in combination with food or beverages, was quantitatively assessed. The taste sensor demonstrated high predictive accuracy, with a significant correlation observed between the sensor's bitter-sensitive outputs and the human taste receptor hT2R14, as documented in BitterDB. Recently, an innovative taste sensor featuring lipid/polymer membranes modified with 2,6-dihydroxybenzoic acid (2,6-DHBA), based on an allosteric mechanism, was developed to improve the detection of bitterness in non-charged compounds. In section (2), PLGA microspheres were engineered for the sustained release of prostaglandin derivatives over one month. Furthermore, polymeric micelles under 100 nm in diameter, composed of PLGA and LL-12 (a mutated fragment of human cathelicidin peptide), exhibited potent antibacterial activity and inhibited the proliferation of various cancer cells. Section (3) focuses on injectable formulations, including the development of a quantitative predictive system to evaluate the risk of insoluble particle formation when mixing ceftriaxone with calcium-containing injections. Additionally, the use of minimum inhibitory concentration (MIC) values and nomograms was explored to predict the clinical efficacy of imipenem derivatives. This research significantly contributes to enhancing the safety and efficacy of clinical treatments for patients.

G-quadruplex (G4) is a unique nucleic acid structure that formed when a four-stranded structure is produced within a single-stranded guanine-rich sequence. Four guanine molecules form a square planar arrangement, termed G-quartet, which are stacked on top of each other to form the G4 structure in DNA (G4DNA) and in RNA (G4RNA). Recent studies have revealed that G4DNA and G4RNA are folded in cells, which suggested their biological and pharmacological significance in DNA replication, transcription, epigenetic modification, and RNA metabolism. In this review, I will provide an overview of G4, its identification methods, and the biological functions "G4 biology" that have been reported, as well as its relevance to the neurological diseases that we have reported. 1) we found a neuropathogenic mechanism, "G4 prionoids" in a CGG triplet repeat disease, Fragile X-associated tremor/ataxia syndrome (FXTAS). 2) G4 is a target of cognitive function therapy for ATR-X intellectual disability syndrome, in which mutations are found in a G4 binding protein ATRX. 3) 5-aminolevulinic acid is a potential candidate drug for treating some neurological diseases through the G4 binding ability.

Creosote, a derivative of coal tar, is used as a wood preservative. In Japan, regulations govern three specific polycyclic aromatic hydrocarbons (PAHs) present in creosote and creosote-treated wood: benzo[a]pyrene, benz[a]anthracene, and dibenz[a,h]anthracene. However, the existing standardized analytical methods in Japan have raised concerns regarding the safety of reagents employed and insufficient purification processes. To overcome these challenges, we developed an analytical method incorporating effective purification techniques, such as centrifugation, silica gel cartridges, and anion exchange cartridges, while eliminating the use of potentially carcinogenic dichloromethane. The validity of this method was evaluated through interlaboratory collaborative tests involving seven institutions. The analysis focused on 10 PAHs, including the three compounds regulated in Japan, across three concentration levels that encompassed current regulatory values. Validation results demonstrated that the method met the trueness and repeatability criteria, established at 70-120% and <10%, respectively. Most reproducibility data satisfied the <15% requirement. Exceptions were observed for two non-regulated compounds in Japan, as well as for samples with high matrix components spiked with the low concentrations of target analytes. The inherent difficulty of analyzing trace compounds in complex matrix components likely contributed to these unsatisfactory results. Despite these limitations, the developed method was validated as suitable for the analysis of at least three regulated PAHs in Japan.

Understanding the molecular-level properties of pharmaceutical formulations is essential for optimizing drug dissolution, stability, and delivery performance. In recent years, the structural complexity of formulations has increased significantly, incorporating multiple functional excipients. In this context, NMR spectroscopy has emerged as a powerful tool for evaluating the physicochemical behavior of active pharmaceutical ingredients (APIs) and excipients across diverse formulation platforms. NMR enables non-destructive, high-resolution analysis of molecular states under various physical conditions, including solids, solutions, and suspensions. Through techniques such as NMR relaxometry, pulsed-field gradient (PFG) NMR, and advanced pulse sequences, NMR provides insight into molecular mobility, miscibility, intermolecular interactions, and phase behavior. These molecular characteristics are closely related to key formulation attributes such as physical stability, dissolution performance, and bioavailability. This review outlines the principles and methodological advances in applying NMR to pharmaceutical formulation research, emphasizing its ability to quantify and differentiate complex coexisting states in situ. By offering direct access to critical molecular information, NMR serves as a diagnostic tool and a foundation for rational formulation design and quality control. As formulation strategies continue to evolve, the role of NMR in guiding the development and evaluation of innovative drug delivery systems is expected to become increasingly important.

Irritable bowel syndrome (IBS) constitutes a chronic functional gastrointestinal disorder characterized by abdominal pain and irregular bowel habits. Diagnosis typically hinges upon symptomatology, following the exclusion of organic pathologies such as intestinal inflammation and malignancies. IBS manifests with diverse symptoms attributable to aberrant intestinal function, including diarrhea, constipation, and bloating, stratified into four types based on the predominance of diarrhea versus constipation. Radical treatment for IBS remains elusive due to its unknown pathology and etiology, thereby necessitating symptom-focused therapeutic approaches. Certain conditions such as psychiatric disorders, intestinal inflammation, food sensitivities, and Small Intestinal Bacterial Overgrowth (SIBO) exhibit overlaps with or correlations to symptoms of IBS, suggesting that treatment targeting these conditions may ameliorate symptoms of IBS. Emotional stress emerges as a principal risk factor for IBS, precipitating alterations in stress hormone levels and intestinal motility, thereby instigating a spectrum of symptoms associated with the disorder. Additional risk factors for IBS exhibit considerable variability among individuals, encompassing dietary factors that stimulate or influence intestinal function, gluten, the presence of fermentable carbohydrates (fermentable oligosaccharides disaccharides monosaccharides and polyols: FODMAPs), and aspects of the intestinal microbiota and its metabolites. Notably, individuals with IBS demonstrate distinctive alterations in gut microbiota composition compared to healthy controls, indicative of dysbiosis. Furthermore, changes in metabolites such as short-chain fatty acids (SCFAs) in some IBS patients are recognized. In summary, while the precise etiology and underlying pathology of IBS remain elusive, management typically necessitates a multifaceted approach involving lifestyle modifications, targeted symptom therapies, occasional psychological support, and adjunctive measures to regulate the intestinal environment.

The escalating crisis of antimicrobial resistance poses a grave threat to global health and medicine in the 21st century. Phage therapy has emerged as a promising alternative to conventional antibiotics in addressing this urgent issue. Phages, unlike traditional antibiotics, leave the healthy microbiome largely undisturbed by selectively targeting and infecting their bacterial host. Additionally, phages can be readily genetically engineered to enhance their efficacy against specific bacterial strains. While some countries are slowly developing new regulations and implementing phage therapy in the clinic, widespread societal adoption remains limited. Phage therapy has the potential to revolutionize infection treatment; however, the unique biological properties of phages necessitate a multifaceted approach for the societal implementation of phage therapy. Recent research has focused on genetically engineering phages to enhance their capabilities or confer novel functions. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have facilitated the development of phages that target specific genes. Furthermore, the emergence of tRNA-carrying phages and phages that inhibit bacterial defense systems represents new classes of genetically engineered phages with enhanced bactericidal properties.

Enantiomers of a chiral compound often exhibit distinct physiological activities, making enantioselective synthesis of chiral molecules a critical challenge in drug discovery. This study explored a novel strategy for converting racemic compounds into a single enantiomer using enzymes, with a focus on developing a methodology to access both enantiomers of chiral esters using a single lipase and enantioconvergent reactions of tertiary alcohols. The desired transformations were achieved by designing multi-catalytic systems that enabled lipases to combine with otherwise incompatible catalysts and reactants using Pickering emulsions as compartmentalized reaction media.

Pesticides, veterinary drugs, and feed additives (hereinafter referred to as "pesticides") can remain in foods when used in agricultural and livestock products. Since consuming a variety of foods every day can result in ingesting trace amounts of these pesticides, which may be harmful to health, risk management for residual pesticides in foods is necessary to prevent adverse effects. Based on the Food Sanitation Act, the Ministry of Health, Labour and Welfare (MHLW) has established maximum residue limits (MRLs) for each pesticide and each food type. Currently, approximately 770 pesticides have MRLs set. Since May 2006, Japan has implemented a positive list system, prohibiting the distribution of food containing residual pesticides exceeding the MRLs or uniform limit of 0.01 ppm for pesticides without established MRLs. Appropriate analytical methods are required to determine whether pesticides exceed the MRLs or uniform limit. Currently, MHLW has notified ten simultaneous analytical methods and approximately 350 individual analytical methods. However, many pesticides still lack developed analytical methods. These methods should be simple, quick, and accurate, but developing them is challenging. The National Institute of Health Sciences, in cooperation with local health institutes, registered conformity assessment bodies, and universities, is working on developing these analytical methods. This lecture introduces an overview and the challenges of analytical methods for detecting residual pesticides.

Mycotoxins, toxic secondary metabolites produced by fungi, are present in food and feed worldwide. Acute and chronic dietary exposures can induce adverse health effects in humans and animals. Among the various mycotoxins, aflatoxins pose significant health concerns to the general public. In the early 1960s, a total of more than 100000 turkey poults died from an unknown turkey "X" disease in England. The disease was associated with Brazilian groundnut meal contaminated by Aspergillus flavus, from which aflatoxins were first isolated from the fungal culture broth. Subsequent studies revealed that aflatoxin B₁ (AFB₁) is the most potent carcinogen among all aflatoxins, affecting both humans and various animal species. The International Agency for Research on Cancer has classified AFB₁ as a Group 1 human carcinogen. Aflatoxins are present in a wide variety of food items, including cereals, nuts, fruits, and spices. A survey conducted in Japan between 2004 and 2006 revealed that peanut products, cacao products, peppers, and Job's tears were contaminated with aflatoxins. To reduce exposure, Japan has set a regulatory limit of 10 µg/kg for total aflatoxins [sum of AFB₁, aflatoxin B₂ (AFB₂), aflatoxin G₁ (AFG₁), and aflatoxin G₂ (AFG₂)] for all food items. The National Institute of Health Sciences has developed official analytical methods for determining aflatoxins in foods which are used for quarantine inspection of imported foods. In this symposium, the regulations and analytical methods for aflatoxins are introduced.