薬理と治療
Volume 48, Issue 4, 2020
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TOPIC
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COS-COVIDの紹介と解説─新型コロナウイルス感染症に対する臨床研究のコア・アウトカム・セットのコンセンサス会議─
48巻4号(2020);View Description Hide Description
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TOPICS 第19回CRCと臨床試験のあり方を考える会議 2019 in YOKOHAMA
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- 受賞演題
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REVIEW
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ORIGINAL ARTICLES
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SGLT2 阻害薬ルセオグリフロジンの長期使用における安全性と有効性の検討―長期使用に関する特定使用成績調査(中間報告)―
48巻4号(2020);View Description Hide DescriptionObjectives To investigate the safety and efficacy of long-term use of the sodium-glucose cotransporter 2(SGLT2)inhibitor luseogliflozin in clinical practice as a specific surveillance of clinical use. This report presents interim results of the surveillance. Methods In luseogliflozin naive patients with type 2 diabetes mellitus (September 2014- May 2016), a specific surveillance was conducted to assess the practical long︱term use of luseogliflozin. The observation period was determined as 36 months from the start of administration. Results In this surveillance, 12,507 patients were included in the safety analysis set, and 12,433 patients were included in the efficacy analysis set. The mean age of the subjects in the safety analysis set (12,507 patients)was 58.6 years. Patients aged<65 years accounted for 65.0%, and patients aged≥65 years accounted for 35.0%. The mean duration of diabetes mellitus was 7.50 years. The mean baseline hemoglobin A1c(HbA1c)was 8.02%, the mean body mass index(BMI)was 28.35, and the mean estimated glomerular filtration rate(eGFR)was 80.93 mL/min/1.73 m2. The mean daily dose of luseogliflozin during the observation period was 2.79 mg, and the mean duration of administration was 702.6 days. As for the status of concomitant use of other antihyperglycemic agents at the start of luseogliflozin treatment, 57.9% of the patients concomitantly used 2 or less antihyperglycemic agents and 22.7% of the patients used none. Adverse reactions occurred in 1197 of the 12,507 subjects in the safety analysis set, with an incidence rate of 9.57%. According to the results from clinical study prior to the approval of this drug, adverse reactions occurred in 236 of 1262 patients, with an incidence rate of 18.7%. Patients were also stratified by eGFR at the start of the treatment, and changes in eGFR were evaluated over time; no significant worsening of eGFR was observed in any patient group. In the subjects in the efficacy analysis(12,433 patients)set, a significant decrease was observed in HbA1c, fasting blood glucose, and body weight. Conclusion The clinical use of SGLT2 inhibitor luseogliflozin was carefully observed over the two-year period, during which no additional safety or efficacy problems were claimed. The interim results of this specific surveillance did not provide additional safety information requiring precaution. In terms of efficacy, the results were similar to the clinical study data obtained prior to the approval of this drug. This surveillance is ongoing, and the results of the final data aggregation and analysis on the long-term use over the three-year period are awaited. -
鮫肝油および乳酸菌の抗インフルエンザウイルス効果―マウスの症状,NK 活性および サイトカイン測定による検討―
48巻4号(2020);View Description Hide DescriptionObjectives This study aimed to investigate the effects of shark liver oil(SLO)and lactic acid bacteria(LAB)on natural killer(NK)activity and cytokine production in mice infected with the influenza A virus. Methods Female BALB/cCrSlc mice were allocated to the control, SLO and LAB groups, and treated orally with water for injection at 0.2 mL/mouse, SLO at 0.2 mL/mouse, and LAB at 2.5 mg/0.2 mL/ mouse, respectively, twice a day for 17 days. On the day 15, influenza A virus PR╱8╱34(H1N1)was nasally infected to the mice. Observation of general signs (once a day)and body weight measurement(twice a week)were conducted until the day 18. On the day 18, spleen was extracted from mice and dispersed. NK activity against YAC-1 cells(mouse leukemia cell line)and cytokines(IL-4, IFN-γ)in culture supernatant of the splenocytes were measured. Results After infection, slight piloerection and hyperpnea were observed in the control and LAB groups. In the SLO group, slight piloerection was observed during administration period. Body weight of the mice in the LSO group significantly increased on the day 18 compared with the control group. As for NK activity, the cytotoxicity of the SLO group was slightly higher than the control group whereas the effect was not statistically significant. The cytotoxicity of the LAB group was comparable to that of the control group. There was no significant difference between the groups as to the IL-4 concentration. The IFN-γ concentration in the LSO group but not of the LAB group was significantly higher than that of the control group. Conclusions It was suggested that the SLO might alleviate the symptoms of influenza virus infection via the facilitation of cytokine production. -
健康な成人におけるぶどう糖ラムネ菓子摂取によるワーキングメモリーと注意力の改善―ランダム化二重盲検プラセボ対照クロスオーバー比較試験―
48巻4号(2020);View Description Hide DescriptionObjective The aim of this study was to investigate the effect of oral ingestion of fizzy candy (Ramune candy)on cognitive function on healthy subjects. Methods A randomized, double-blind, placebo-controlled cross-over, comparison study was conducted in 14 healthy subjects(Mean±SD 33.9±1.3, Median 35.5 years old). The subjects were given either the test product(29 g Ramune candy containing 26 g hydrous crystal glucose, Morinaga & Co., Ltd., Tokyo)or the control product (placebo candy not containing glucose)30 min before the Japanese version of the CNS Vital Signs(Cognitrax). Results The cognitrax individual tests scores of 4-part continuous performance test related to working memory and sustained attention were significantly improved in the Ramune group compared to the placebo group. Conclusions The results suggested that oral ingestion of 26 g hydrous crystal glucose may be effective for cognitive function. (UMIN-CTR000036893) -
加熱殺菌した乳酸菌Enterococcus faecalis KH2株の摂取が健常な日本人成人の腸内環境に及ぼす影響と安全性の検討―ランダム化二重盲検プラセボ対照並行群間比較試験―
48巻4号(2020);View Description Hide DescriptionObjective We assessed heat treatment Enterococcus faecalis strain KH2 in terms of safety and efficacy for increasing amount of defecation in a randomized placebo controlled double-blind paralleled study. Methods This study included a total of 30 healthy Japanese adult volunteers 30-59 aged years who were selected by defecation frequency two to five times a week. Subjects were randomly assigned to two groups(KH2 group or placebo group). Subjects consumed powder preparation containing of 100 mg KH2 and 900 mg dextrin mixture or 1000 mg dextrin daily for 1 week. Intestinal microflora was assessed using terminal restriction fragment length polymorphism analysis(T-RFLP)at baseline and one week after the start of administration KH2 or placebo. Results A total of 25 subjects(KH2 group, n=10;placebo group, n=15)completed the study. At one week after the start of the test-food consumption, the primary endpoint, amount of defecation which was evaluated by using Japanese version of constipation assessment scale (CAS-MT), was significantly high in KH2 group(P=0.01). The secondary endpoint, the change amount of occupying rate of Clostridium cluster Ⅳ in intestinal microflora was also significantly high in KH2 group(P=0.003). Safety parameters and incidence of adverse events did not differ significantly between two groups. Conclusion These results indicate that promoting defecation by ingestion of KH2 and improving the intestinal environment. Conclusion These results indicate that promoting defecation by ingestion of KH2 and improving the intestinal environment. -
コーヒー豆由来クロロゲン酸の単回摂取が健常男性の冷えに及ぼす影響―プラセボ対照ランダム化二重盲検クロスオーバー群間比較試験―
48巻4号(2020);View Description Hide DescriptionObjectives The aim of this study was to examine the effect of ingesting coffee chlorogenic acid(CGA)on skin temperature after cold water stress in healthy Japanese males. Methods A randomized, double-blind, placebo-controlled, crossover intervention study was conducted on 24 healthy Japanese males who were cold-sensitive. A cold stress test(exposure to water temperature at 15℃ for 5 minutes)was performed on both hands after acclimating them in a 33℃ water bath for 30 minutes. Each subject ingested a test beverage(CGA-270 mg, CGA-135 mg or a placebo)45 minutes before the cold stress test with a one-week washout period between them. Skin temperature of the hands was measured before ingesting each beverage and at 2.5 minute intervals for 30 minutes immediately after the cold stress test. As an index of CGA efficacy, the recovery rate of skin temperature was calculated based on the skin temperature before and after the cold stress test. Results Twenty-two subjects completed this study. The recovery rate of skin temperature after the cold stress test was significantly improved in subjects who ingested CGA-270 mg compared with the placebo(P=0.003). No significant difference was observed in subjects who ingested CGA-135 mg compared with the placebo. Conclusions A single ingestion of CGA-270 mg improved skin temperature after a cold stress test in healthy Japanese males and CGA is expected to improve the QOL that was reduced by cold. This study is registered with UMIN Clinical Traials registry(ID:UMIN000029931) -
桑の葉エキス配合飲料摂取による食後血糖値上昇抑制効果検証試験―ランダム化二重盲検プラセボ対照クロスオーバー比較試験―
48巻4号(2020);View Description Hide DescriptionObjectives The aim of this study was to evaluate an effect of the beverage containing mulberry leaf extract on the postprandial blood glucose level. Methods Seventy six volunteers were randomly assigned to 2 groups and conducted as a randomized double-blind placebo-controlled cross-over study. The volunteers ingested 200 g rice with a test beverage containing 500 mg mulberry leaf extract or a placebo beverage. The blood glucose levels and insulin levels were measured before and 30, 60, 90, 120 and 180 minutes after the intake of the test beverage. The GLP-1 levels were measured before and 30, 60 minutes after the intake of the test beverage. Results Ingestion of the test beverage containing mulberry leaf extract inhibited the elevation of postprandial blood glucose levels. Conclusions This study suggested that ingestion of the test beverage containing mulberry leaf extract reduced the postprandial blood glucose levels. UMIN000037576 -
Maltobionic Acid Enhances Absorption of Minerals in Healthy Humans―A Randomized Double—blind Placebo—controlled Crossover Study(Part 1)―
48巻4号(2020);View Description Hide DescriptionBackground/Objectives This study investigated the effects of maltobionic acid (corn syrup containing maltobionic acid)ingestion on mineral absorption in healthy Japanese adult males and females. Methods This was a randomized, double-blind, placebo-controlled, crossover study. Thirty-five healthy Japanese adult males and females were allocated into three groups: Test food 1 (corn syrup containing maltobionic acid 2 g, maltose syrup 2 g), Test food 2(corn syrup containing maltobionic acid 4 g), and Placebo food(maltose syrup 4 g). Intestinal mineral absorption was assessed by calculating the change in the serum and urinary mineral content and the percentage of retained minerals in the body during the study period. Safety was assessed by physical examination and physician interview. Results The final efficacy analyzer was the full analysis set, with a total of 29 subjects(16 males and 13 females). After maltobionic acid ingestion, the change from before to after intake in urinary excretion of calcium, magnesium, iron, and sodium was significantly higher than that after the ingestion of placebo, indicating an intervention effect. Maltobionic acid appears to efficiently promote mineral absorption in the whole intestine, both the small and large intestine, by maintaining the solubilization state of the mineral in the intestine unlike the mineral absorption promotion effect which depends on the large intestine fermentation. Conclusions Intake of maltobionic acid in healthy Japanese adult males and females may contribute to the efficient bioavailability of minerals by maintaining the solubilization of minerals and rapidly and persistently exerting mineral absorption-promoting effects in the intestinal tract.(UMIN-CTR ID: 000034976) -
Maltobionic Acid Enhances Absorption ofMinerals in Healthy Humans―A Randomized Double—blind Placebo—controlledCrossover Study(Part 2)―
48巻4号(2020);View Description Hide DescriptionBackground/Objectives In this study, we aimed to investigate the effects of ingestion of maltobionic acid(corn syrup containing maltobionic acid)on mineral absorption in healthy Japanese adult men and women. Methods Thirty-five healthy Japanese adult men and women were tested through a randomized, double-blind, placebo-controlled, crossover study. They were allocated into three groups:Test food 1(corn syrup containing maltobionic acid 2 g, maltose syrup 2 g); Test food 2 (corn syrup containing maltobionic acid 4 g); Placebo food(maltose syrup 4 g). Intestinal mineral absorption was assessed by calculating the change in the serum and urinary mineral content, and the percentage of retained minerals. Safety was assessed through physical examination and physician interviews. Here, we report comparisons between Test food 2 and Placebo food. Results The final efficacy was assessed with a total of 29 subjects(16 males and 13 females). The intake of maltobionic acid resulted in increased calcium and magnesium in the urine. Maltobionic acid seemed to efficiently carry out intestinal absorption(throughout the small intestine and large intestine)of minerals by maintaining the solubilization state of the minerals in the intestine, unlike the mineral absorption promotion effect that depends on large intestine fermentation. Conclusions Thus, the intake of maltobionic acid may contribute to the efficient bioavailability of minerals by maintaining the solubilization of minerals while rapidly and persistently exerting mineral absorption promoting effects in the intestinal tract in healthy Japanese adult men and women. (UMIN-CTR ID: 000034976) -
ユーグレナグラシリスEOD—1 株含有食品の長期摂取安全性試験―ランダム化二重盲検プラセボ対照並行群間比較試験―
48巻4号(2020);View Description Hide DescriptionObjective The aim of this study was to evaluate the safety of the long-term intake of food containing Euglena gracilis EOD-1. Methods A randomized, double-blind, placebo-controlled, parallel-group comparison study was conducted in healthy adults(n=40)as to the safety of long-term intake. The subjects ingested either a placebo or a test food containing 500 mg of E. gracilis EOD-1 daily for 12 weeks. Results No unusual changes related to the intake of E. gracilis EOD-1 were observed in physical, blood, and urinary examinations. Side effects and adverse events related to the intake of E. gracilis EOD-1 were not observed. Conclusions These results indicated that the long-term ingestion of 500 mg/day of E. gracilis EOD/1 was safe. (UMIN-CTR ID: UMIN000036101) -
大豆由来フォスファチジルセリン含有サプリメント飲用による健常高齢者の認知機能改善―ランダム化プラセボ対照二重盲検並行群間比較試験―
48巻4号(2020);View Description Hide DescriptionBackground It is important to establish the methods to prevent aging-related deterioration of cognitive functions by daily taking of functional foods or supplements in the current aging society. Phosphatidylserine is a phospholipid abundantly contained in the cell membrane, and plays important roles in neuronal functions in brain. Though effects of the oral intake of phosphatidylserine have been investigated in the past few decades, conditions of these reports, including the amount, base material of phosphatidylserine and the tests to evaluate cognitive functions, were varied, and their effects on cognitive functions remained still unclear. Methods We performed a randomized, double-blind, placebo-controlled parallel-group comparative study to evaluate the improvement of cognitive functions of 40 elderly persons over the age of 60, by daily intake of phosphatidylserine supplement from soybean(126 mg/day)for 6 weeks, by using following three tests, generally used for the cognitive functions: Mini Mental State Examination(MMSE), Benton visual retention test, and Standard verbal paired-associate learning test. Results After the daily intake of phosphatidylserine supplement from soybean for 6 weeks, total score of MMSE and the score in the calculation showed significantly improvement in the test product group, while placebo group showed no significant improvements. Scores in other tests did not showed significant statistical differences in both groups, with the exception that the score of unrelated dialogue in the standard verbal paired-associate learning test showed significant decreased only in the placebo group. Conclusion Our results indicate that regular intake of the phosphatidylserine supplement from soybean is effective for the improvement of specific cognitive functions of elderly persons, especially for the performance using working memories. -
健常者および軽度認知障害者に対するエルゴチオネイン含有食品の認知機能改善効果―ランダム化プラセボ対照二重盲検並行群間比較試験―
48巻4号(2020);View Description Hide DescriptionObjective Ergothioneine is a hydrophilic amino acid that is abundantly contained in mushrooms, and reported to have an antioxidant effect, a neurogenic effect, and a memory improvement effect. The purpose of this study is to evaluate the effect of ergothioneine on cognitive function in humans. Methods We conducted a randomized, placebo-controlled, double-blind, parallel-group study for 52 healthy volunteers(18 men and 34 women, including those with mild cognitive impairment).Subjects consumed either a tablet containing 5 mg ergothioneine as the test food (provided by LS Corporation Co., Ltd.)or a tablet not containing ergothioneine as the placebo. Cognitrax test was used to assess cognitive function before and 4, 8, and 12 weeks after consumption of the test food. Results The consumption of ergothioneine significantly improved Psychomotor Speed compared with the placebo group. In addition, stratified results for subjects in the cognitive function domain of Foods with Function Claims showed significant improvements in Verbal Memory, Simple Attention, and Sustained Attention compared with the placebo group. No adverse events attributable to the test food were observed in any subjects during the study. Conclusion These results indicate that continuous intake of ergothioneine improves cognitive function in healthy subjects(normal subjects and those with mild cognitive impairment). (UMIN 000034386) -
自立高齢者に対する栄養調整食品の継続摂取による栄養改善効果に関する検討
48巻4号(2020);View Description Hide DescriptionObjective We investigated the effect of oral enteral nutrition on nutritional status in non-institutionalized elderly participants. Methods We examined the effects of a 12-week intervention of the enteral nutrition on the nutritional status in 82 non-institutionalized elderly participants in the Asuke Hospital. Results The MNA®-SF score at the end of this study was significantly increased compared to the score at the start of intervention. The improvement in the MNA®-SF score was greater in malnourished participants and participants at risk for malnutrition during the study period, than in well-nourished participants. In addition, triceps skin fold thickness (TSF)was significantly increased during the study period in malnourished participants and participants at risk for malnutrition. Conclusions These findings suggest that the 12-week nutrition intervention improves the nutritional status in non-institutionalized elderly participants. -
Fat—burning Effect of OleaVita® Consumption―A Randomized, Placebo—controlled, Double—blind,Parallel—group Comparison Study―
48巻4号(2020);View Description Hide DescriptionObjective We examined the effects of an ethanol/water extract of olive leaves (EEO, trade name: OleaVita®), which has a fat-reducing effect, on human energy metabolism. Methods A randomized, placebo-controlled, double-blind, parallel-group comparison study was conducted from February to April 2019 in healthy Japanese adults with a body mass index of≥23 to<30 without an excessive daily exercise routine. The subjects were randomly assigned to an EEO or placebo group (n=20 per group)and each group took either one EEO capsule(OleaVita®)or placebo capsule daily for 8 weeks. The primary outcomes were body weight, waist diameter, fatigue visual analog scale(VAS), and respiratory quotient(RQ). Results The final efficacy analysis involved 19 subjects each in the EEO and placebo groups. In the subgroup analysis, the subjects in a per-protocol se(t PPS)whose low-density lipoprotein cholesterol level at screening was≤139 mg/dL were extracted. The PPS revealed no significant differences between groups. In the subgroup analysis, the change in RQ between the rest time and after the 30-min-exercise-load in the EEO group was significantly lower than that in the placebo group at 8 weeks after intake(P=0.008). No adverse events attributable to the test food were observed. Conclusions The results suggest that continuous intake of an EEO for 8 weeks increases fat-burning efficiency. Clinical trial registration number UMIN-CTR: UMIN000035750. Funder Nutrition Act Co., Ltd.
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BRIEF COMMUNICATION
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加熱殺菌した乳酸菌Enterococcus faecalis のクロストリディオイデス・ディフィシルに対する増殖抑制効果
48巻4号(2020);View Description Hide DescriptionObjectives In this study, we evaluated the effect of a Heat-killed lactic acid bacteria Enterococcus faecalis(HkEf)for inhibiting the proliferation of Clostridioides difficile(C. difficile). A in vitro study was performed to assess the direct effect between HkEf and C. difficile. Methods C. difficile was co-cultured with HkEf(0.64 mg/mL or 64 mg/mL)in an anaerobic condition, the amount of viable bacteria was estimated by counting the number of colonies immediately after incubated, after12h, 14h and 48h. Results Under the both condition, the number of C. difficile are significantly decreased at 12h, 14h and 48h after incubated, compared to the control group. The number of viable bacteria colonies at 48h after incubated, are decreased to about 1╱1000(HkEf:0.64 mg╱mL)and to about 1╱10,000(HkEf:64 mg╱mL), compared to the control group. Conclusions The results suggested that HkEf has a direct effect to inhibit the proliferation of C. difficile.
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