薬理と治療

慢性便秘症治療薬の処方実態と患者の服薬意識を把握するため，アンケートデータ，調剤レセプトデータおよび薬歴データをマッチングさせたハイブリッド調査を行った。その結果，非刺激性下剤が定期処方される患者は高齢で，生活習慣病を合併している多剤併用例が多かった。また，薬剤師は非刺激性下剤が定期処方される患者に対してケア計画を立案し，不定期処方される患者に対して副作用に関する指導を行うケースが多かった。さらには，定期処方群では医師の指示どおりに服用する患者が多かったのに対して，不定期処方群では減らして服用する患者が多かった。以上のことから，非刺激性下剤が処方される患者の背景と薬学的介入内容が明らかとなり，患者の服薬習慣や服薬意識が非刺激性下剤の処方に影響を及ぼすことが示唆された。【利益相反】本研究を行うにあたり，㈱社会情報サービスはマイランEPD 合同会社の資金提供を受けた。その他の筆者については，開示するべき利益相反はない。

Background Infection︱induced septic disseminated intravascular coagulation （DIC）is a lethal condition. Recombinant human soluble thrombomodulin（rTM）has gained considerable attention as an anticoagulant treatment. Therefore, this study evaluated the therapeutic efficacy of rTM for DIC. Methods This retrospective study evaluated 77 cases that were diagnosed with DIC（using the standard criteria for acute DIC）and treated using rTM. Sixty-two cases were diagnosed as infection-induced septic DIC（62╱77; 80.5％）. In addition to rTM, these 62 patients received various blood products as therapy for septic DIC（antithrombin Ⅲ, 23 cases; fresh frozen plasma, 26 cases; and heparin, 23 cases）. Results There were significant differences in the pre- and post-rTM treatment scores for acute DIC（except for the Ministry of Health, Labour and Welfare score）, Acute Physiology and Chronic Health EvaluationⅡ, Sequential Organ Failure Assessment, and lung injury. The DIC resolution rate and 28-day survival rate after rTM treatment were 72.7％（56╱77）and 64.9％（50╱77）, respectively. When we evaluated the 62 cases of infection-induced septic DIC, the DIC resolution rate and 28-day survival rate were 75.8％（47╱62）and 69.3％（43╱62）, respectively. Compared to the group that did not receive antithrombin Ⅲ, the group that received antithrombin Ⅲ with rTM（n＝23）exhibited significantly differences in platelet count, prothrombin time-international normalized ratio, antithrombin Ⅲ levels, and D-dimer levels. Conclusions Treatment with rTM is appropriate for DIC, and this studyʼs findings suggest that rTM is effective for infection-induced septic DIC.

Objectives As there has been no report on the effect of isomaltodextrin（IMD）on bowel movements in humans, we performed a study to examine the effect in adult women who have 2 to 4 defecations per week. Methods A double-blind, placebo-controlled, crossover study was conducted. Nine subjects were assigned to two groups so that each group had the same number of defecations per week. The subjects received 15 g of IMD（test substance）or 15 g of maltodextrin（MD） （control substance）once daily for 4 weeks, each separated by a 4-week washout period. The water content, pH, and short chain fatty acids（SCFAs）in subjectsʼ feces were determined before intake, and at weeks 2 and 4 during the intake. The subjects filled in a questionnaire on defecation and symptoms. Results The number of days of defecations was significantly higher in IMD intake than in MD intake at week 4. A significant improvement by IMD intake was also noted in a Visual Analog Scale questionnaire on defecation. Furthermore, the amount of total SCFAs in feces was increased after the intake of IMD with a significantly higher Δ value（change from the baseline）in IMD intake than in MD intake at week 2. Conclusions Based on the above, the intake of IMD（15 g╱day）is considered to improve bowel movements.

Objective A randomized, double-blind, placebo-controlled study was conducted to assess the effects of freeze-dried aronia tablets including anthocyanin on eye fatigue in healthy subjects. Methods Twenty-six healthy adult participants who worked with VDTs and have eye fatigue were screened by an ophthalmologist. Participants were allocated to either an aronia group（n＝13）or a placebo group（n＝13）, who ingested 5 aronia or placebo tablets, respectively, per day for 4 weeks. Eye fatigue asperity was measured at 0 and 4 weeks by accommodative function test, flicker test, and subjective symptom analysis. Safety was evaluated by physical examination, urinalysis, blood test, and ophthalmologic examination. Results Of the 26 participants, 2 subjects from the aronia group dropped out of the study because of the lack of test food intake. Therefore, the final analysis included 11 and 13 participants in the aronia and placebo groups, respectively. After intake of the appropriate test food, the accommodative function after 45 min of VDT load was significantly improved in the aronia group compared with that in the placebo group（P＜0.05）. The assessment of flicker test and subjective symptoms related to eye fatigue were not different between groups. No medical changes or safety concerns were observed by physical examination, urinalysis, blood test, or ophthalmologic examination. Conclusion These results suggest that the intake of freeze-dried aronia tablets improve eye fatigue after VDT load in healthy Japanese adults. In addition, the intake of aronia tablets was safe under the conditions used in this study.

Objective The purpose of this study was to examine the effects of β-cryptoxanthin-containing paprika oleoresin on the quality of life（QOL）of healthy subjects with mild knee pain. In addition, we evaluated the safety of β-cryptoxanthin-containing paprika oleoresin as our second aim. Methods This clinical study was conducted as a randomized, double-blind, placebo-controlled, parallel-group comparison trial in healthy adult volunteers with mild knee pain. In total, 32 volunteers were randomly divided into two groups, ingesting either test capsules containing 20 mg of paprika oleoresin（paprika group）or placebo capsules（placebo group）for 12 consecutive weeks. In this study, QOL was evaluated using the Japanese Knee Osteoarthritis Measure（JKOM）at 0, 6, and 12 weeks after the first ingestion. Plasma interleukin-6（IL-6） levels, serum high-sensitivity C-reactive protein levels, and serum carotenoid levels were measured at 0 and 12 weeks. To evaluate the safety of β-cryptoxanthin-containing paprika oleoresin, we conducted hematological, blood chemical, and urine analyses. Results Visual analog scale and JKOM scores were significantly reduced in both groups after 6 and 12 weeks of ingestion, and no significant differences were seen between the two groups. However, general activities, which are subscales of JKOM, showed significantly lower scores in the paprika group than in the placebo group. Moreover, the plasma IL-6 levels were significantly decreased in the paprika group, and the serum β-cryptoxanthin levels were higher in the paprika group than in the placebo group after 12 weeks of ingestion. No adverse effects associated with paprika extract intake were observed during the safety evaluation.Conclusion These results suggest that β-cryptoxanthin-containing paprika oleoresin improves QOL related to joint health.

Objectives We developed a fermented tea by mixing of camellia leaves and third crop green tea leaves at the ratio of 1：9. Feeding a freeze-dried fermented tea extract suppressed white adipose tissue weight and serum and hepatic triglyceride concentrations in SD rats. We investigated the effect of long-term feeding the mixed fermented tea on serum triglyceride levels in dialysis patients. Methods All subjects were dialysis patients. In the first experiment, 11 subjects were divided into the two groups, and 8 subjects were fed the fermented tea extracted 0.5％ tea leaves with hot water and 3 subjects were fed green tea or brown rice tea for 3 months. In the second experiment, 27 subjects were fed the fermented tea for 1 month. The amount of the fermented tea leaves used in experiment 2 was 1.5 times higher than that of tea leaves used in experiment 1.Results The concentrations of serum triglyceride were lower, but not significant, in the subjects fed the fermented tea than in those fed green tea or brown rice tea during 3 months. Feeding the 1.5 times stronger fermented tea significantly reduced serum triglyceride level at 1 month after the start of feeding fermented tea. Conclusions These results suggest that a fermented tea made by mixing camellia leaves and third crop green tea leaves has the lowering activity of serum triglyceride concentration in dialysis patients.

Background The aim of this study was to demonstrate the effects of this combination on serum liver enzymes, emotional states, and inflammatory markers to clarify the contribution of systemic inflammation to serum liver enzymes and emotional states. Methods Eighty healthy participants with moderately high body mass index were assigned to a 12-week treatment with a combination of hot water extract of Curcuma longa（400μg as bisacurone）and curcumin（30 mg）or placebo in a randomized, double-blind, placebo-controlled design. Results For all participants, serum liver enzyme levels did not significantly differ between the combination and the placebo groups. However, for participants whose serum liver enzyme levels were in the borderline range, decreases in serum liver enzymes （alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase）were significantly greater in the combination group than in the placebo group（P＝0.047, 0.035, and 0.0014, respectively）. Although there were no significant differences in changes in inflammatory marker levels between the placebo and the combination groups, these levels showed a significant decrease in participants whose serum liver enzyme levels had improved. The combination group showed a significantly greater decrease in fatigue scores on the Profile of Mood States（POMS）than the placebo group（P＝0.0007）. Conclusions This study showed that a combination of hot water extract of Curcuma longa and curcumin significantly decreased serum liver enzyme levels of participants with borderline serum liver enzyme levels, possibly through the suppression of systemic inflammation. Additionally, the combination significantly decreased POMS fatigue scores.

Objective The study aimed to verify the efficacy on knee joint and safety of dietary supplement containing Proteoglycan complex 80 derived from salmon nasal cartilage. Methods A randomized, double-blind, placebo-controlled, parallel-group study was conducted for 60 participants（51.7±6.9 years）who ingested dietary supplement containing 40 mg of Proteoglycan complex 80 produced from salmon nasal cartilage or placebo for 12 weeks. The Japanese Orthopaedic Association（JOA）score, Japanese Knee Osteoarthritis Measure（JKOM）score, Knee Society Score（KSS）, and Visual Analogue Scale（VAS）questionnaire were used for evaluation of knee joint function. Results The JOA and JKOM scores, KSS and the results of VAS questionnaire were significantly improved between dietary supplement and placebo after 12 weeks. Side effects related to intake of Proteoglycan complex 80 were not confirmed on this study. Conclusion These results strongly suggest that the dietary supplement containing Proteoglycan complex 80 from salmon nasal cartilage is effective for improving knee joint functions and safe.

Objective The oyster drink“Watanabe Oyster Drink”contains essential amino acids and trace metals as well as 3,5-dihydroxy-4-methoxybenzyl alcohol（DHMBA）, a phenolic antioxidant. The aim of this study was to examine the effects of the intake of the oyster extracts on stress, fatigue, and sleep conditions in adult volunteers who felt stress and fatigue. Methods Adult volunteers（84 subjects）were enrolled in a randomized, double-blind, placebo controlled, parallel-group study. Subjects ingested 2 bottles of either DHMBA-containing oyster extract drink or placebo drink daily for 4 weeks. The conditions of stress, fatigue, and sleep were evaluated by the Short form of Profile of Mood States（POMS-S）, the Japanese version of the Pittsburgh Sleep Quality Index （PSQI︱j）, and the Athens Insomnia Scale（AIS）. Results In POMS-S, the changes from pre-trial values of depression score at week 3 and week 4（－17.5±13.4 and －19.0±11.8）and fatigue score at week 2（－15.1±11.1）in oyster extract drink group were significantly lower than those in placebo group（－11.1 ±12.2, －13.6±11.0, －9.9±10.0, respectively；P＜0.05）. The sleep efficiency in PSQI︱j was significantly better in DHMBA-containing oyster extract drink group compared to placebo drink group. There were no adverse events related to the intake of the test drinks. Conclusions Our results suggest that the intake of DHMBA-containing oyster extract drink alleviates mental stress and fatigue, and improves sleep.

Objectives We investigated changes in physical functions（i.e., agility, balance, strength, and gait）of healthy middle-aged adults consuming milk-derived milk-fat globule membrane （MGFM）containing sphingomyelin. Methods A randomized, double-blind, placebo-controlled study was conducted with 56 healthy middle-aged adults（age range 50-69 years）. The subjects were asked to consume either MFGM tablets（MFGM containing 33 mg of sphingomyelin, 1 g╱day）or placebo tablets （whole milk powder, 1 g╱day）during the 8-week study period and to participate in a light exercise program（3-3.5 Mets）for 30 min twice a week. Physical performance（10-sec step counts, one-leg standing duration, and chair stand counts）and walking performance（10-m walking speed and obstacle walking speed）, and questionnaires（MOS 36-Item Short-Form Health Survey ［SF-36］and“Daily life physical function questionnaire”）were evaluated. Results In the MFGM group, changes from week 0 to week 8 of 10-sec step counts, one-leg standing duration, chair stand counts, 10-m walking speed, and obstacle walking speed were significantly improved. Improvement of obstacle walking speed and one-leg standing duration were significantly different between MFGM group and placebo group. These findings suggest that MFGM ingestion leads to better balance and faster walking time. Findings from the questionnaire suggest that subjects in the MFGM group noticed the improvements in physical and walking function（especially walking and stair-climbing performance）. Conclusions MFGM containing sphingomyelin improved physical balance and walking function of healthy middle-aged adults. Thus, MFGM may be helpful for improving locomotive syndrome.