薬理と治療
Volume 48, Issue 5, 2020
Volumes & issues:
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扉・目次
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TOPIC 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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- シンポジウム12 /まわりの人が協力的に動いてくれる? CRC の調整力─院内外のコーディネーションのアイデア─
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SYMPOSIUM
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イノベーティブな医薬品の評価と新たな薬価システムの枠組みの検討
48巻5号(2020);View Description Hide DescriptionBackground In recent years, a number of innovative drugs have emerged that show innovative evidence of effectiveness. Both of them meet the medical needs of the patients, but they often involve high drug priced and high volumes, especially in the short-term increase in drug costs immediately after launch, and the financial impact to budget in government. The Japanese market must be stable and attractive in order for Japan to continue to be the first in the world to provide innovative medicines with priority and continuity. Methods In order to specify and discuss the issues, a workshop entitled“Workshop on the Significance and Challenges of Pharmaceutical Innovation Evaluation”was held in August and December 2019. Furthermore, in order to visualize the current situation and identify budget impacts, we analyzed data with Japanese high priced and high-volume drugs. Results The issues were specified, and the evaluation of innovative drugs within the available financial resources and the introduction of a drug pricing system based on the evaluation were examined. We considered incentives to reflect the value of pharmaceuticals, setting special priority for innovative drugs, macroeconomic slides to secure resources for special priority, limiting drug costs, and adjusting allocation ratios. Conclusion We discussed the drug price system in different shades, such as the establishment of special priority subject to appropriate valuation and restrictions on the scale of drug costs. We hope that this issue and discussion will be discussed in more places, and in addition to how insurance benefits should be provided, based on the opinions of the public.
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ORIGINAL ARTICLES
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All—trans—Retinoic Acid Prevents Colorectal Carcinogenesis in Mice with Ulcerative Colitis
48巻5号(2020);View Description Hide DescriptionObjectives Retinoids have indicated efficacy for treating acute promyelocytic leukemia. The retinoids have proven to be effective in inducing cellular differentiation and suppressing proliferation in numerous tumor cell lines. An increased incidence of colorectal carcinoma is known to occur in patients with ulcerative colitis, which displays a cycle of recurrence-remission, i.e. periods of ulceration and regeneration of the colorectal mucosa. Methods Three-time administrations of 3% dextran sulfate sodium subsequent to a single intraperitoneal injection of azoxymethane induce a chronic ulcerative colitis resulting in an increase of high-grade dysplasia and submucosal-invasive adenocarcinomas in the mouse colorectum. Hence, the effects of all-trans retinoic acid, one of retinoids, on colorectal carcinogenesis in mice with ulcerative colitis were investigated. Results Additive treatment with all-trans retinoic acid prevented shrinkage of the colorectum, which was affected by a cycle of recurrence-remission in colorectal mucosa, resulting in a reduced incidence of colorectal dysplasia and a reduced expression of thymidine kinase mRNA in the colorectum. Conclusion The findings may suggest that all︱trans retinoic acid inhibit colorectal inflammation and/or carcinogenesis and its development as an inhibitor of colorectal epithelial cell proliferation and the neoplastic process, or as a promoter of cellular differentiation. -
緑藻 クロレラChlorella pyrenoidosa より得られたペプチドヘテログリカンのヒト癌型K—ras 遺伝子発現誘導型肺腺癌マウスにおける抗癌効果
48巻5号(2020);View Description Hide DescriptionBackground In the present study, we investigated the antitumor effect of a peptidoheteroglycan prepared from Chlorella pyrenoidosa(Chlorophyceae)on oncogenic K-rasG12V mediated lung adenocarcinoma formation in mice. Methods We examined on the antitumor effect and immune-histopathological test by the intraperitoneal administration using oncogenic K-rasG12V driven lung adenocarcinoma genesis bearing mice. Results The tumor was demonstrated to be oncogenic K-rasG12V driven lung adenocarcinoma. In the group intraperitoneal administration with peptidoheteroglycan 20 mg/kg every other day, a highly significant inhibition was observed as compared with the control group and complete regression of the tumor occurred in 20%. Conclusions It is known that human oncogenic K-rasG12V are detected 25-30% in lung, 70-90% in pancreas, and -50% in colon with cancer patients. It was suggested that intraperitoneal administration of peptidoheteroglycan may have a tumor suppressive effect on lung adenocarcinoma, pancreas and colon cancers in cancer patients by this experiment. -
ピセアタンノールおよびコラーゲンペプチド,エラスチンペプチド,ヒアルロン酸4 糖との組合わせが線維芽細胞でのヒアルロン酸合成へ与える影響
48巻5号(2020);View Description Hide DescriptionObjective The aim of this study was to investigate whether piceatannol(PIC) induces hyaluronan synthesis in cultured fibroblasts. In addition, the effect of treatment with combination of PIC, collagen-derived dipeptide prolyl-hydroxyproline(Pro-Hyp), elastin-derived dipeptide prolyl-glycine(Pro-Gly)and hyaluronan tetrasaccharide(HA4)on hyaluronan synthesis in cultured fibroblasts was evaluated. Methods The mRNA expression level of hyaluronan synthase 1(HAS1)and hyaluronan synthase 3(HAS3)in cultured fibroblasts after treatment with PIC were evaluated by quantitative real-time PCR. The mRNA expression level of HAS1 in cultured fibroblasts after treatment with combination of PIC, Pro-Hyp, Pro-Gly and HA4 was also investigated. Results The mRNA expression of HAS1 and HAS3 were upregulated by PIC in cultured fibroblasts. In addition, treatment with combination of PIC, Pro-Hyp, Pro-Gly and HA4 upregulated HAS1 mRNA expression. Conclusions These results suggest that PIC, Pro-Hyp, Pro-Gly and HA4 might affect skin moisture by inducing hyaluronan synthesis in dermal fibroblasts. -
Regular Use of Laxatives Influence Dose of Dopaminergic Medication in Patients with Parkinsonism
48巻5号(2020);View Description Hide DescriptionPatients with neurodegenerative parkinsonian diseases often take medications for constipation. Thus far, few studies have investigated the association between the regular use of constipation medications and the use of dopaminergic medication in patients with neurodegenerative parkinsonian diseases. In addition, no reports have classified constipation medications according to the mechanism of action and evaluated the levodopa equivalent dose(LED). This study analyzed 163 patients with neurodegenerative parkinsonian diseases who had been taking levodopa at the time of admission to the Department of Neurology, Fukuoka University Hospital from January 2016 to December 2018. Patients who regularly used constipation medications were defined as constipation medication users. Ninety-two patients (56.4%)who had neurodegenerative parkinsonian diseases regularly used constipation medications. The regular use of constipation medications was associated with the number of medications taken(odds ratio 1.292, 95% confidence interval 1.121︱1.490). The LED of neurodegenerative parkinsonian disease patients who regularly used stimulant laxatives was significantly higher in comparison to those who did not regularly use constipation medications(P<0.05). Further studies should be performed to investigate whether stimulant laxatives affect the absorption of therapeutic agents due to hypofunction of the intestinal tract. -
焙煎コーヒー(高クロロゲン酸類含有コーヒー)による内臓脂肪減少効果および安全性の検討
48巻5号(2020);View Description Hide DescriptionThe chlorogenic acids had been reported as the polyphenols in coffee that decrease visceral fat. Therefore, that will effect to treat metabolic syndrome. Then, we made the chlorogenic acids-enriched ground coffee by specific roasting technique, and examined the efficacy in reducing visceral fat and the safety in healthy but obese volunteers. In this study, 48 healthy volunteers were divided into two groups by double blind method and each group took a cup of coffee every day that contained either low dose(0-50 mg)as control coffee group or high dose(270-330 mg)of chlorogenic acids as active coffee group for 12 weeks. Before and 12 weeks later of this study, biochemical blood tests and urine tests were examined. Every 4 weeks, anthropometry(BMI, visceral fat area and waist size)was measured. On every visit, healthy condition, meal analysis and major events in each 4 weeks was checked by medical staffs. As the results, in the high dose group, serum triglyceride decreased significantly after 12 weeks, and visceral fat area significantly decreased on 4th week and 12th week. In the blood and urine examination, blood pressure, heart rate and subjective symptom did not show adverse effects. In conclusion, compared with control coffee, the chlorogenic acids︱enriched coffee was significantly effective and safe to decrease visceral fat and serum triglyceride. -
桑の葉エキス含有食品の反復摂取による血糖上昇抑制効果確認試験―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5号(2020);View Description Hide DescriptionObjectives The aim of this study was to evaluate the effect of a food containing Mulberry leaf extract on blood glucose level. Methods A randomized double-blind placebo-controlled parallel group study was conducted in sixty healthy volunteers. The volunteers were randomly assigned to three groups and given test beverage containing 0, 250, 500 mg mulberry leaf extract daily for 12 weeks. For the efficacy assessment, the volunteers ingested 200 g rice with test beverages and the postprandial blood glucose level was measured. Moreover, insulin, hemoglobin A1c (HbA1c), homeostasis model assessment for insulin resistance(HOMA-IR), 1, 5-anhydroglucitol (1.5AG), as indicators for glucose metabolism. Results Ingestion of the test food containing mulberry leaf extract inhibited the elevation of postprandial blood glucose. But, this time, it was not possible to confirm the effect of lowering fasting blood glucose level and improvement in glucose metabolism by continuous ingestion of mulberry leaf extract. Conclusions This study suggests that ingestion of test foods containing mulberry leaf extract reduce the postprandial blood glucose level. (UMIN 000034752) -
Effect of Water—soluble Dietary Fiber from Candida utilis on Postprandial Serum Triglyceride and Safety Evaluation of Long—term and Excessive Intake of C. utilis Extract in Healthy Subjects―Randomized, Double—blind, Placebo—controlled, Crossover and Parallel Group Study―
48巻5号(2020);View Description Hide DescriptionObjectives Here, we investigated whether the water-soluble Candida utilis cell wall (TPF) could suppress the postprandial elevation of serum triglyceride(TG)levels and evaluated the safety of excessive and long-term intake of glucanase-treated yeast(TP). Methods To test the effects of TPF intake, a randomized double-blind placebo-controlled crossover study was performed in 42 healthy adults. The subjects ingested a solution containing 900 mg of TPF or dextrin(placebo)with high fat meal(containing 46.4 g fat). Blood samples were taken before and 1, 2, 3, 4, 5, and 6 h after food ingestion and serum TG were measured. To evaluate the safety of long-term and excessive intake of TP in healthy adult subjects, a randomized double-blind placebo-controlled parallel-group study was performed. For the long-term intake trial, the subjects were given 5 g of TP or casein protein each day for 12 weeks. For the excessive intake trial, the subjects were given 15 g of TP or casein protein each day for 4 weeks. Results Postprandial serum TG levels were significantly suppressed at 3, 4, and 5 h after the ingestion of TPF with a high fat meal compared with those of placebo(P<0.05). TPF intake significantly lowered the area under the curve of postprandial serum TG(P<0.05). Adverse effects and clinically relevant changes in blood and urinary parameters were not observed during these safety evaluations. Conclusions These results suggest that water-soluble dietary fiber from C. utilis has an inhibitory effect on elevated postprandial serum TG levels and is safe for human consumption. -
Monoglucosyl Rutin Facilitates Recovery from Eyestrain in Visual Display Terminal Users―A Randomized, Placebo—controlled, Double—blind, Crossover Study―
48巻5号(2020);View Description Hide DescriptionBackground Eyestrain is a serious quality of life problem, especially in the workplace. In particular, work at visual display terminals(VDTs)is a common cause of eyestrain. Monoglucosyl rutin(MGR)is a highly water-soluble α-glucose adduct of rutin. Previous studies have demonstrated that rutin improved dry eye. Thus, we hypothesized that MGR could alleviate eyestrain caused by work at VDTs. In this clinical study, we evaluated whether MGR could improve eyestrain in healthy adults.Method This study was designed as a randomized, placebo-controlled, double-blind, crossover study. Twenty healthy Japanese adults who tended to feel eyestrain were recruited to participate. During the first test period, the participants were asked to drink either a test food containing 352 mg of MGR or a placebo food without MGR. After the food intake, the participants did personal computer work at VDT for 30 min and then relaxed for 20 min. We evaluated the participantsʼ eyestrain using an objective parameter(high-frequency component 1, HFC1)and subjective parameters(visual analog scale). After 7 days, for the second test period, the participants consumed an alternate food following the same protocol as during the first test period. Results The objective parameter of eyestrain(HFC1)was significantly lower in the MGR group than that in the placebo group. The subjective parameters of eyestrain and waist stiffness were improved in the MGR group in comparison with those in the placebo group. Conclusion MGR supplementation has the effect to objectively and subjectively improve eyestrain symptoms due to VDT use. Trial registration UMIN000026566 -
The Effect of Food Containing Pueraria Flower Extract on Energy Metabolism―A Randomized, Double—blind, Placebo—controlled, Parallel—group Study―
48巻5号(2020);View Description Hide DescriptionObjectives We performed a randomized, double-blind, placebo-controlled, parallel-group study in healthy males who were asked to ingest food containing Pueraria flower extrac(t PFE) to investigate the effects of the oral intake of Pueraria thomsonii flower isoflavones tectorigenin, tectoridin, and tectorigenin 7-O-xylosylglucoside(PFIF)on energy metabolism in healthy adults. Methods Eighty healthy men aged 30-39 years, whose body mass indexes(BMI)were ≥20 and <25 were enrolled in the study and randomly divided into two groups: those who ingested a food with(active group)or without(placebo group)PFE over an 8-week period. The effects of exercise on energy metabolism were evaluated in an examination at the start of ingestion(0-week examination)and at post-ingestion(8-week examination). Results Changes in energy expenditure(EE)at 8 weeks after ingestion[(8-week examination)-(0-week examination)], i.e. ΔEE was significantly increased in the active group compared with that in the placebo group(P<0.05). There were no adverse events related to the test food during the study. Conclusions Overall, these results indicate that intake of PFIF can increase EE on energy metabolism in healthy adults. (UMIN-CTR ID: UMIN000036693) -
トマト由来食物繊維の食後血糖値に対する有効性検証およびその構成糖の解析―プラセボ対照クロスオーバー比較試験―
48巻5号(2020);View Description Hide DescriptionObjective Tomato-derived dietary fiber(TDF)is suggested to attenuate postprandial blood glucose elevation by suppressing or delaying absorption of glucose, but the patterns of effects were inconsistent between previous 2 studies. Here, we conducted an intervention study with a TDF-fortified test beverage to confirm the effect. We also analyzed the constituent sugars in TDF to clarify the qualitative characteristics. Methods A placebo-controlled, crossover study was conducted. Placebo(P)and TDF-fortified beverage(T)were used. Fifty healthy subjects consumed either of the 2 beverages at immediately before eating 150 g of cooked rice. Blood glucose levels, maximum concentration of Δblood glucose levels (ΔCmax), incremental area under the curve(IAUC)were compared between P and T group. Also, the constituent sugars in dietary fibers extracted from 7 tomato products and 5 other vegetables and fruit(carrot, petit vert, kale, red bell pepper, lemon)were analyzed by HPLC. Results T suppressed blood glucose levels at 15, 30, and 45 min, ΔCmax, IAUC60 min, IAUC90 min, and IAUC120 min compared with P. The effects were clearer than that in the previous studies. The main constituent sugar in TDF was glucose, and it also contained xylose and mannose at a constant ratio. This was clearly different from the other dietary fibersʼsugar composition. Conclusions The clinical study clearly shows the suppressive effects of TDF on postprandial blood glucose. Also, the constituent sugar composition of TDF is suggested to be distinctive compared with other vegetables/fruits-derived dietary fibers. (UMIN ID: UMIN000039601) -
A Study on the Effect of Food Containing Pine Bark Extract on Vascular Endothelial Function―A randomized, Double—blind, Placebo—controlled, Parallel—group Study―
48巻5号(2020);View Description Hide DescriptionObjectives A randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate the effect of food containing pine bark extract(PBE)on vascular endothelial function in healthy subjects. Methods Forty healthy subjects with a body mass index(BMI)<30 were enrolled in the present study. The subjects were randomly divided into two groups and ingested either a food containing pine bark extract or a food without pine bark extract(placebo)for 8 weeks. Vascular endothelial function was evaluated by flow-mediated dilation(FMD)measured before, and at 4 and 8 weeks following ingestion. Results After 8 weeks, FMD improved significantly in the PBE group compared with the placebo group(P<0.05). Conclusions These results indicate that the food containing pine bark extract improves the vascular endothelial function in healthy subjects. (UMIN-CTR ID: UMIN000036602) -
桑葉粉末摂取による食後血糖値上昇抑制効果の検証―ランダム化プラセボ対照二重盲検クロスオーバー試験―
48巻5号(2020);View Description Hide DescriptionObjectives Mulberry leaves have been used as feed for silkworms and consumed as a beverage or health food. This plant is characterized by containing immino-sugars. We evaluated effects of low dose immino-sugars on postprandial blood glucose levels. Methods A randomized, placebo controlled, double-blind, crossover study was conducted for 22 healthy adult volunteers(10 males and 12 females aged from 21 to 64 years)with fasting blood glucose levels less than 126 mg/dL. Subjects consume either placebo or test food, followed by carbohydrate loading diet, and the levels of blood glucose and insulin were determined after 30-120 min. Results Intake of the test food significantly suppressed the elevation of postprandial blood glucose levels compared to that in the placebo group. The value at 30 min after the intake of test food(114.9±15.7 mg/dL)was significantly lower than that of placebo(128.2 ±15.7 mg╱dL, P<0.01). Total area under the curve of blood glucose level was 12,8385±1508 mg・min╱dL in the test group and 13,143±1742 mg・min╱dL in the placebo group(P<0.01). Conclusions These results suggested that low dose immino-sugars had suppression effect on the elevation of postprandial blood glucose level. -
Effects of Solid, Lipid Curcumin Particles on Alcohol Metabolism―An Exploratory and a Randomized, Double—blind, Placebo—controlled, Parallel—group Crossover Study―
48巻5号(2020);View Description Hide DescriptionIntroduction This study examined effects of Longvida® Optimized Curcumin®, with various probable physiological activity effects, on alcohol metabolism. Methods A randomized, double-blind, placebo-controlled, parallel-group crossover study was conducted in healthy Japanese males. The alcohol patch test was used to select a total of 15 subjects who did not exhibit extremely low alcohol tolerance. Subjects were divided into two groups: test food group(containing Longvida®)and placebo food group. The primary and secondary outcomes were assessed before and up to 180 min after alcohol loading. The primary outcomes were measured with blood alcohol and acetaldehyde levels and breath alcohol levels. The secondary outcomes were determined by a questionnaire survey. Results One subject withdrew consent during the study; thus, 14 subjects were included in the final analysis. No significant differences were found between the groups regarding blood or breath alcohol levels. Blood acetaldehyde level in the test food group 180 min after alcohol loading was significantly lower than that in the placebo food group. Conclusion The results of this study suggest that Longvida® Optimized Curcumin® enhances the metabolism of blood acetaldehyde after alcohol consumption. Traial Registration Japan Primary Registries Network UMIN000014995
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CASE REPORT
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COLUMN
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INFORMATION
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