薬理と治療

Objectives　This study aimed to evaluate pharmacotherapy pattern of MOVICOL®（macrogol＋electrolytes（E））, to evaluate risk factors associated with macrogol＋E discontinuation, and to evaluate the pattern of concomitant use of stimulants or saline laxatives during macrogol＋E treatment in a real–world setting using an extensive electronic medical records database that primarily includes data from acute care hospitals. Methods　Data of patients prescribed for macrogol＋E from April 1, 2018, to March 31, 2022, were extracted from the database. The discontinuation of macrogol and stimulant or saline laxatives during macrogol＋E treatment was evaluated using the Kaplan–Meier method. The Cox proportional hazards model evaluated risk factors associated with laxative discontinuation. Results　In total, 8233 patients were evaluated. Higher retention with PEG＋E was observed in patients diagnosed with constipation, pediatric patients younger than 12 years, patients with Parkinsonʼs Disease, patients suffering from dementia, those patients with previous laxative treatment as well as constipated psychiatry patients. The prescription rate of stimulants and saline laxatives markedly decreased after macrogol initiation; furthermore, nearly half of the patients who were continuously prescribed macrogol＋E discontinued these laxatives within 360 days. Conclusions　Observing the pharmacotherapy patterns for macrogol＋E, valuable insight in duration of therapy and concomitant medication amongst various patient groups has been obtained. Furthermore, it has been observed that the concomitant use of stimulants and/or saline laxatives decreased to manage the treatment of（chronic）constipation. it seemed to be useful for the control of the chronic constipation. （UMIN000048352）（Jpn Pharmacol Ther 2024；52：253‒67）

Background　Atopic dermatitis（AD）is a multifocal disease with a complex pathogenesis such as exposome. The use of topical sunscreens to reduce skin exposure to solar radiation is an integral part of the strategy to suppress the exacerbation of signs and symptoms of AD patients. Objectives　To assess the safety and protecting effect of a new sunscreen in infants and children with AD applying on face at least 4 days a week in consecutive 4 weeks. Methods　Thirty infants and children aged between 2 months and under 6 years old with AD were enrolled（5 months―5 years and 6 months, average 3.47 years old）. Their severity index of AD was ranked as mild or moderate. Skin symptoms（dryness/desquamation, erythema, papule, infiltration, scratch marks, lichenification）, subjective symptoms（skin irritation and itching）and adverse events were examined on week 0, 2 and 4 by dermatologists. Results　Safety of the sunscreen was confirmed to every subject（30/30 judged as safe）with the evaluation of skin symptoms, subjective symptoms and adverse events. No adverse reaction was observed. One subject was dropped out because of a fever by cold and excluded from usefulness assessment. Skin symptoms and subjective symptoms were mostly stable without exacerbation during 4 weeks in the residual all 29 subjects. Although explicit improvements were rare, stable findings on these skin symptoms would suggest that the sunscreen played a pivotal role in skin protection. Conclusions　The new sunscreen is safe for infants and children with mild to moderate AD and available for skin protection to sun exposure. （UMIN000051240）（Jpn Pharmacol Ther 2024；52：269‒80）

The objective of this study was to evaluate the effect of oral ingestion of FlαX®–Iso, a formula of Peucedanum japonicum Thunb. leaf extract standardized by isosamidin concentration and highly–oxidation–resistant flaxseed oil, on the improvement of overactive bladder（OAB）symptoms in Japanese OAB patients in 8–week, randomized, double–blind, placebo controlled, parallel clinical trial. Eighty–eight patients were divided into 2 groups（FlαX®–Iso and placebo）and overactive bladder symptom score（OABSS, at baseline, 4th, and 8th week）, overactive bladder questionnaire（OAB–q, at baseline, 1st, 2nd, 4th, and 8th week）, and frequency of urination（at baseline and every week during the study period）were compared. After 1–week of administration, for OAB–q, the change in score of symptom bother, impact on quality of life （QOL）, concern/worry, and sleep（both subitem of impact on QOL）were significantly better and this was kept until 8–week. For the frequency of urination, daytime frequency and 24h frequency were significantly improved after 8–week. For OABSS, we couldnʼt observe any significant improvement. No adverse events were observed. In summary, FlαX®–Iso improved the objective and subjective parameters of OAB symptoms in OAB patients and also demonstrated that this may act good alternative medicine for individuals with OAB.（Jpn Pharmacol Ther 2024；52：281‒94）

Objective　This study aimed to verify the effects of consuming food containing high–（108.0 mg/day）or low–dose（36.0 mg/day）of seabuckthorn pulp oil for 8 weeks on skin environment in healthy adult Japanese women. Methods　This randomized, double–blind, placebo–controlled, parallel–group comparative study enrolled 99 participants who met eligibility criteria, among the 141 individuals who provided informed consent. The participants were randomly assigned to one of the three groups （allocation ratio 1：1：1）using a computer. Participants in placebo, low–dose, and high–dose groups were instructed to take four capsules containing 0 mg/day, 36.0 mg/day, and 108.0 mg/ day doses of seabuckthorn pulp oil, respectively, with water per day for 8 weeks. Participants were evaluated based on parameters, such as skin moisture（cheek; Corneometer® CM 825）, transepidermal water loss（cheek; Tewameter® TM300）, skin elasticity（cheek; Cutometer® dual MPA 580）, sebum amount（cheek; Sebumeter® SM815）, and subjective skin symptoms. The primary outcome was skin moisture after the 8–week intervention. Results　All participants completed this study and were included in the “intention–to–treat” analysis. While no significant effects on skin moisture were observed, temporary improvements in skin flexibility, shape resilience, and elasticity and some subjective skin symptoms were noted in the low–and high–dose groups after 4 weeks of intake. Although the precise effect of oral seabuckthorn pulp oil intake remains unclear from this study alone, it is suggested that it helps maintain skin elasticity. Conclusions　The consumption of 36.0 or 108.0 mg/day of seabuckthorn pulp oil could be useful for maintaining a healthy skin environment in healthy adult Japanese women aged 25–72 by having beneficial effects on skin elasticity. Trial registration　UMIN000048541 Foundation　Gifu Shellac Manufacturing Co., Ltd.（Jpn Pharmacol Ther 2024；52：295‒309）

Objective　To examine the effects of foods containing matured red ginseng extract（MRGE）on the sleep quality of healthy Japanese adults with poor sleep quality. Methods　A randomized, placebo–controlled, double–blind, parallel–group comparison study was conducted on a total of 108 participants who were randomly assigned in a 1：1：1 ratio to MRGE–216 mg/day group, MRGE–324 mg/day group, or placebo group via a computer generated random number. The participants were asked to consume two tablets per day of food containing MRGE or a placebo with water at any time of the day for 12 weeks. The primary outcome was“sleepiness on rising”as assessed using the OSA Sleep Study MA（OSA–MA） after the 12–week intervention. Results　The efficacy dataset was the per protocol set, with 35 participants in each of the MRGE–216 mg/day and placebo groups and 36 participants in the MRGE–324 mg/day group. Compared to the placebo group, the primary outcome of OSA–MA, “sleepiness on rising,”significantly improved in both MRGE groups, while“sleep length”significantly improved only in the MRGE–216 mg/day group. In addition, some of the subcategories of“sleepiness on rising” and“sleep length”improved in the MRGE–216 mg/day and 324 mg/day groups compared to the placebo group. Conclusions　These results indicated that 12–week daily consumption of a food containing MRGE improved sleep quality（waking up refreshed, sense of having slept longer, and sleep satisfaction）in healthy Japanese adults with poor sleep quality. Trial registration　UMIN000047707 Foundation　KIMʼs Korean Ginseng Co., Ltd.（Jpn Pharmacol Ther 2024；52：311‒29）

Objective　To examine the effects of consuming foods containing matured red ginseng extract （MRGE）on fatigue and stress in healthy Japanese adults with subjective fatigue and stress on a daily basis. Methods　This randomized, placebo–controlled, double–blinded, and parallel–grouped comparison study involved 111 participants. The participants were randomly assigned with computer generator to MRGE–216 mg/day group, MRGE–324 mg/day group, and placebo group, in a 1：1：1 ratio. Each day for 12 weeks, participants consumed two tablets of food containing MRGE or placebo with water at any time of the day. The assessment items were subjective fatigue quantified using a visual analog scale, autonomic function tests, and oxidative stress–related biomarkers. The difference in subjective fatigue before and after the mental fatigue load with the Uchida–Kraepelin test was the primary outcome. Results　The efficacy data set was per protocol set（PPS）, including 36 participants from the placebo, 34 from the MRGE–216 mg/day, and 37 from the MRGE–324 mg/day groups. Compared to the placebo group, both MRGE groups showed a significant improvement in subjective fatigue before and after the mental fatigue load. The MRGE–324 mg/day group also showed significant improvement in subjective fatigue after the mental fatigue load. In the PPS and＜43 years old subgroups, the biological antioxidant potential, which indicates antioxidant capacity, was significantly improved in both MRGE groups compared to the placebo group. Conclusions　These results demonstrate that 12–week daily consumption of MRGE–containing foods temporarily improves subjective fatigue（e.g., general malaise, lethargy, weakness, tiredness）in healthy Japanese adults. Trial registration　UMIN000047704 Foundation　KIMʼs Korean Ginseng Co., Ltd. （Jpn Pharmacol Ther 2024；52：331‒56）

Objective　To examine the effects of matured red ginseng extrac（t MRGE）–containing food on improvement body temperature in healthy Japanese adults with cold hypersensitivity in hands and feet. Methods　This randomized, placebo–controlled, double–blind, parallel–group comparison study included 56 participants, randomly assigned in a ratio of 1: 1 to MRGE（216 mg/day）or placebo groups via a computer–generated random number. The participants consumed two tablets of MRGE–containing food or a placebo daily with water at any time of the day for 12 weeks. Palm skin surface temperature and blood flow before and after cold–water load, and subjective symptoms related to cold hypersensitivity in the hands and feet were evaluated. Cold–water loading was immersing hands in approximately 15℃ water at for 1 min. The primary outcome included the area under the curve（AUC）of the palm skin surface temperature, immediately to 30 min after the cold–water load. Results　The efficacy dataset was the per protocol set, with 26 participants in each of the MRGE and placebo groups. The MRGE 216 mg/day group demonstrated a significantly higher AUC immediately to 30 min after the cold–water load at 12 weeks after intake, and marginally improved coldness of fingertips than in the placebo group. No adverse events were observed. Conclusions　The 12–week intake of MRGE–containing food significantly increased palm skin surface temperature restoration in response to the cold–water load, significantly suppressed the decrease in palmar surface temperature, and markedly reduced the subjective fingertip coldness. These results demonstrate that thermoregulatory effect of MRGE maintains the warm surface temperature of the fingertips. Trial registration　UMIN000047708 Foundation　KIMʼs Korean Ginseng Co., Ltd.（Jpn Pharmacol Ther 2024；52：359‒91）

Objective　To investigate the effects of matured red ginseng extract（MRGE）on subjective shoulder stiffness symptoms in healthy Japanese adults. Methods　A double–blind, placebo–controlled, randomized, parallel–group comparison trial was conducted in 56 participants randomly assigned, via computer, to one of two groups（28 participants per group）. The participants were instructed to consume either MRGE（216 mg/day）–containing food（MRGE group）or a placebo（placebo group）for 12 weeks. The assessment items included a questionnaire to evaluate subjective symptoms（including“My shoulder and neck are stiff”and“My eyes are tired”）associated with visual display terminals（VDT）operation, conducted before and after VDT workload with 60 min. The primary outcome measure was“My shoulder and neck are stiff”following VDT workload at the post–intervention assessment. Results　The efficacy analysis dataset comprised 25 participants from the MRGE and 27 participants from the placebo groups. Compared to the placebo group“, My shoulder and neck are stiff”was significantly lower in the MRGE group, both before and after VDT workload. Moreover, in participants aged≥31 years“, My eyes are tired”was significantly lower in the MRGE group compared to the placebo group following VDT workload. These findings suggest that MRGE effectively alleviated subjective symptoms. No adverse events were observed. Conclusions　The consumption of MRGE significantly alleviated subjective symptoms of shoulder stiffness in healthy Japanese adults experiencing shoulder stiffness due to VDT work （i.e., tasks requiring focus and intensity）.Trial registration　UMIN000047710 Foundation　KIMʼs Korean Ginseng Co., Ltd.（Jpn Pharmacol Ther 2024；52：393‒411）

Objectives　We conducted a cross–sectional study to examine the relationship between immunological parameters and lifestyles by healthy adults. Methods　Salivary secretory immunoglobulin A（sIgA）concentrations, sIgA secretion rates, Natural Killer（NK）cell activities, and lifestyle questionnaires were examined to 542 subjects in Japanese men and women more than 20 years old. The questionnaire included questions on exercise, diet, and other lifestyle habits, such as drinking and smoking. Results　No correlations were found between salivary sIgA and lifestyles in full analysis set. Salivary sIgA secretion rates were negatively correlated age（Spearman rank correlation coefficient, r＝－0.1063, P＝0.019）in analysis set on excluding outliers. 　　Multiple regression models showed that higher NK cell activity was significantly associated with intake of yogurt（P＝0.010）, and men（P＝0.010）. Conclusions　These results suggest that intake of yogurt helps to improve the decline in immune function associated with aging. （Jpn Pharmacol Ther 2024；52：413‒34）

Objectives　An additional study was conducted using samples from a previously published randomized, double–blind, placebo–controlled, parallel–group study to evaluate the effects of food containing heat–killed Lactobacillus rhamnosus CRL1505（HkLr05）on the immune functions of healthy participants. In this study, we aimed to evaluate the expression levels of interferon–alpha（IFN–α）, a potent indicator of immune cell activation that reflects the primary function of plasmacytoid dendritic cells（pDCs）, and the antiviral gene MX dynamin–like GTPase 1（Mx1）, an indicator of antiviral activity. Methods　An efficacy study was conducted on 80 healthy participants. The participants were randomly divided into two groups and administered either food containing HkLr05 or placebo for 8 weeks. Their immune functions were evaluated by determining the expression levels of IFN–α and Mx1 in peripheral blood mononuclear cells（PBMCs）at baseline and 4 and 8 weeks after ingestion. Results　After 8 weeks, IFN–α and Mx1 expression levels were significantly higher in the HkLr05 group than in the placebo group（P＜0.05）. Conclusions　These results indicate that HkLr05–containing food induces plasmacytoid dendritic cell activation and the antiviral immune response. （UMIN–CTR ID: UMIN000046351, UMIN000052860）（Jpn Pharmacol Ther 2024；52：435‒41）

誤差と残差はほぼ同じ意味で使われることもあり，混乱することも大変多い用語です。本来はどのように違うのかを考えてみたいと思います。