薬理と治療
Volume 44, Issue 9, 2016
Volumes & issues:
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扉・目次
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SERIES 機能性表示食品制度における届け出されたレビューの現状と課題
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REVIEWS
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ORIGINAL ARTICLES
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高齢2 型糖尿病患者におけるカナグリフロジンの特定使用成績調査(中間報告)―高齢者の特性をふまえて―
44巻9号(2016);View Description Hide Description目的高齢2 型糖尿病患者を対象としたカナグリフロジン(販売名カナグル® 錠)の特定使用成績調査の中間報告として,実臨床における安全性および有効性を検討した。方法販売開始3 ヵ月以内(2014 年9 月3 日~12月2 日)に本剤の投与を開始した65 歳以上の高齢2型糖尿病患者全例を対象に,中央登録方式にて特定使用成績調査を実施している。2016 年3 月までに調査票が収集された症例について中間解析を実施した。加えて,年齢(75 歳未満および75 歳以上)と投与開始時点のeGFR(60 mL╱分╱1.73 m2以上および60 mL╱分╱1.73 m2未満)による部分集団についての解析も行った。結果調査票収集症例1067 例のうち,安全性解析対象症例1060 例における副作用発現割合は8.30%(88╱1060 例)であり,おもな副作用は,便秘,口渇が7 例(0.66%),浮動性めまいが6 例(0.57%),膀胱炎,脱水,湿疹,そう痒症,発疹および頻尿が各5 例(0.47%)であった。本調査の副作用発現割合は,国内臨床試験における割合を超えるものではなかった。安全性解析対象症例のうち後期高齢者の症例は366 例(34.5%)であった。年齢別の各集団における副作用発現割合は,75 歳未満の集団が9.37%(65╱694 例),75 歳以上の集団が6.28%(23╱366 例)であり,明らかな差は認められなかった。また,eGFR 別の各集団間についても明らかな差は認められなかった。有効性解析対象症例990 例における本剤投与6 ヵ月時および12 ヵ月時のHbA1c の平均変化量はおのおの-0.64%,-0.87%であり,国内臨床試験の報告と同程度の結果が確認された。年齢およびeGFR 別のHbA1c 変化量についても各集団間で明らかな差は認められなかった。結論本調査の中間集計の結果,カナグリフロジンを投与した高齢2 型糖尿病患者において,新たに臨床上問題となる副作用は認められず,年齢およびeGFR 別の各部分集団における安全性についても各集団間で明らかな違いは認められなかった。【利益相反】本特定使用成績調査は,第一三共㈱へ一部委託のもと,田辺三菱製薬㈱が実施した(JAPIC 登録番号:JapicCTI︱153049)。筆者全員が田辺三菱製薬㈱の社員であり,利益相反に相当する事項はない。【謝辞】本調査を進めるにあたり,ご多忙のなか,ご協力をいただきました先生方に深く感謝いたします。 -
足関節固定モデルラットの痛覚過敏に対する抑肝散の効果
44巻9号(2016);View Description Hide Description目的足関節固定モデルラットの足関節可動閾(ROM)と痛覚過敏に対する抑肝散の効果について検討した。方法実験にはWistar 系雄性ラットを用いた。3%抑肝散含有固形飼料CE‒2 を実験期間中(2 週間)自由摂取させた(抑肝散2.4 g/kg/day)。効果を比較するため,pregabalin 10 mg/kg/day 腹腔内投与群とpentazocine 30 mg/kg 皮下投与群を作製した。右後足関節固定1 および2 週間後に足関節背屈ROM を測定,von Frey test とplantar test により疼痛行動を評価した。すべての結果は左足(コントロール)に対する右足の値を百分率で示した。結果足関節固定2 週間後,背屈ROM は66%と有意に制限された。この制限に薬物投与の影響はなく,いずれも67%以下を示した。足関節固定2 週間後,機械的痛覚過敏と熱刺激に対する痛み反応はそれぞれ39%,76%と有意に減少したが,抑肝散投与により,この減少は抑制された。一方,pregabalin やpentazocine 投与によってもこの痛覚過敏は抑制されたが,眠気やふらつきを観察した。結論以上の結果より,抑肝散は足関節固定モデルラットに対して痛覚過敏を抑制することが明らかとなった。眠気やふらつきを伴わない抑肝散の投与は手術や外傷に伴うギプス固定による治療後の痛みに対して有効であると考えられる。【利益相反】開示する利益相反はない。 -
感作モルモットの抗原誘発遅発型気道抵抗におけるCysLT2受容体の関与
44巻9号(2016);View Description Hide DescriptionExposure of sensitized animals to antigens brings immediate asthmatic response characterized by β2-stimulant-sensitive bronchoconstriction and late asthmatic response characterized by β2-stimulant-resistant persistent airway inflammation. To examine implication of cysteinyl leukotriene 2(CysLT2)receptors in late asthmatic response, we evaluated effects of cysteinyl leukotriene 1(CysLT1) receptor antagonist(montelukast)and CysLT1 and CysLT2 receptor dual antagonist (ONO-6950)on late phase airway resistance and pulmonary eosinophil infiltration followed by ovalbumin(OVA)challenge in actively sensitized guinea pigs. The experiments were performed with or without the treatment of S-hexyl GSH, because S-hexyl GSH can elicit CysLT2 receptor dependent airway responses in guinea pigs as we have previously reported. In non-S-hexyl GSH treated guinea pigs, ONO-6950(3 mg╱kg, p. o.)and montelukast(1 mg╱kg, p. o.)equally attenuated OVA-induced increase in late phase airway resistance. On the other hand, in S-hexyl GSH-treated guinea pigs only ONO-6950, but not montelukast, significantly inhibited OVA-induced increase in late phase airway resistance. Number of eosinophils recovered from bronchoalveolar lavage fluid 22-24 hours after OVA challenge was equally reduced by montelukast and ONO-6950 regardless of S-hexyl GSH treatment. This result suggests that CysLT2 receptors as well as CysLT1 receptors play an important role in the development of late phase airway resistance. Therefore, ONO-6950, orally active dual CysLT1╱LT2 receptor antagonist, is expected to improve airway inflammation more potently than montelukast, CysLT1 receptor antagonist. -
L—シスチンの投与は低タンパク食マウスの体毛タンパク質量を増やす
44巻9号(2016);View Description Hide DescriptionObjective L-Cystine is the oxidized dimer of cysteine in keratin from hair and nail. There are few data of the oral administration of L-Cystine to affect the quality of hair. In this study, we evaluated the oral administration of L-Cystine to increase the hair protein in low protein diet mice. Methods 6-weeks-old C3H╱HeJYokSlc male mice were divided into three groups as follows; Standard diet, Low protein diet, Low protein with L-Cystine diet. After five weeks to orally administration of test diet, hair was collected from back skin on mice. Hair protein was extracted and determined the amount of matrix and microfibril protein. The amount of matrix and microfibril protein from hair was determined with the band intensity of its SDS-PAGE. Results The amount of matrix and microfibril protein of low protein diet mice hair was lower than that of the standard diet mice hair. The protein content of low protein with L-Cystine diet mice hair was significantly increased that of low protein diet mice hair. Conclusions Oral administration of L-Cystine increased the hair protein in low protein diet mice. It is considered that the oral administration of L-Cystine increased the amount of hair protein. -
柿葉熱水抽出液の正常高値血圧者およびⅠ度高血圧者に対する8 週間摂取による血圧降下作用と安全性―プラセボ対照ランダム化単盲検並行群間比較試験―
44巻9号(2016);View Description Hide DescriptionBackground Hot water extract of persimmon leaves(traditionally called as persimmon leaf tea)has been widely consumed in Japan and has already been found to have blood pressure (BP)lowering effect through endothelium-dependent vasodilation by our in vitro and animal studies. The aim of this study was the clinical evaluation of the BP lowering efficacy and safety of the extract. Method A single-blind, randomized, placebo-controlled study for 8 weeks was conducted in 27 subjects with high-normal BP(prehypertension, systolic 130╱diastolic 85-139╱89 mmHg) and stageⅠ hypertension(140╱90-159╱99 mmHg). They were enrolled to three groups, to consume 350 mL╱day of one of either placebo, extracts from 4 g(low-dose), or extracts from 8 g(high︱dose)of dried persimmon leaves(polyphenol contents, 0, 280, and 560 mg╱day, respectively). Primary outcome measure was change in BP after 2, 4, 6, and 8-weeks of daily intake. Secondary outcome measures included changes in flow mediated dilation(FMD)and safety evaluation for 8-weeks intake. Conclusions These results suggested that the intake of persimmon leaf extract would be useful for lowering BP in subjects with high normal BP and stageⅠ hypertension and have no safety concern for long-term intake. Results High dose group was found to have trends toward lower systolic BP after 2, 6, and 8-weeks(P=0.070, 0.093, 0.070, respectively), compared with placebo group, although low dose group had no significant change. In FMD, both dose groups showed no significant change. No abnormal change caused by the test beverages was observed in the physical, biochemical and blood examinations in addition to medical interview. Conclusions These results suggested that the intake of persimmon leaf extract would be useful for lowering BP in subjects with high normal BP and stageⅠ hypertension and have no safety concern for long-term intake. -
プラセボ対照二重盲検並行群間比較試験によるOligonol(R) の耳鳴り軽減作用の検証
44巻9号(2016);View Description Hide DescriptionBackground In Japan, 10-20% of people are troubled with tinnitus. Although its mechanism is not elucidated, it is suggested that blood flow and temperature around ear auricle relate to tinnitus. Oligonol(R), a low molecular weight polyphenol from lychee fruit, is known to have the various physiological functions such as elevation of body temperature by improving blood flow. Thus, the ameliorative effect of Oligonol(R) on tinnitus was investigated. Methods A randomized, double-blind, placebo-controlled exploratory study in healthy subjects with mild tinnitus was conducted. The subjects took 100 mg╱day of either Oligonol(R) or placebo once a day for four weeks. Tinnitus Handicap Inventory(THI), Visual Analog Scale(VAS)including tinnitus symptom and quality of life(QOL), and eardrum temperature were evaluated. Results The VAS score for“coldness on the hands and feet”in the Oligonol(R) group was significantly improved compared to the placebo group. Additionally, the VAS score for“frequency of asking what has been said”in the Oligonol(R) group showed a tendency to improve compared to the placebo group. Furthermore, the VAS scores fo“r influence on sleep by ear noise”“, dizziness” and“coldness on the hands and feet”in the Oligonol(R) group were significantly improved after four weeks compared to the initial. The eardrum temperature was significantly decreased in the placebo group while the Oligonol(R) group showed no significant change in the eardrum temperature. Conclusion These results suggest that Oligonol(R) improves the condition of tinnitus and consequently enhances QOL. -
Hypotriglyceridemic Effect of Kale ―A Randomized, Double—blind, Parallel—group,Placebo—controlled Study―
44巻9号(2016);View Description Hide DescriptionBackground Kale has health-promoting potentials. Our preliminary open-label study suggested that the intake of kale lowers serum triglyceride(TG)level in subjects with baseline serum TG levels of 150-199 mg╱dL. Objective The aim of this study was to confirm hypotriglyceridemic effect of kale in a randomized, double-blind, parallel-group, placebo-controlled study. Methods/study design We enrolled 78 volunteers whose fasting serum TG levels ranged from 120-199 mg╱dL. Subjects were randomly allocated to 3 groups; placebo(group P), low-dose(7g daily)kale (group L), and high-dose(14 g daily)kale(group H). The period of intake was 12 weeks. Two subjects(1each in group P and H)dropped out, and 76 subjects completed the study. After excluding 5 subjects(2 in group P; 3 in group H)who met the exclusion criteria for efficacy analysis, data obtained with 71 subjects were analyzed for efficacy. Results There was a marginal decrease in serum TG level in group H at the 8th week in the analysis of the whole subject population. In subjects with baseline TG levels of 150-199 mg╱dL, significantly lower TG levels (P<0.01)were observed in both group L and group H (150.8±35.1 and 139.3 ±55.9 mg╱dL, respectively)compared to the level in group P(215.3 ±47.9 mg╱dL)at the 8th week. No serious adverse event was observed during this study. Conclusion Our results suggest that daily intake of 7-14 g of kale benefits persons whose serum TG level is slightly higher than the normal range. -
ラクトフェリン含有食品が健常な成人の免疫グロブリンA 分泌能,腸内環境および睡眠感に与える影響―無作為化プラセボ対照二重盲検比較試験―
44巻9号(2016);View Description Hide DescriptionObjectives Immunoglobulin A(IgA)plays a major role in a maintenance of well-balanced and diverse gut microbiota. The aim of this study was to investigate the effects of lactoferrin (LF)supplementation for 4 weeks on IgA secretion, enteric environment, sleep quality and mood states in healthy adults. Methods Sixty healthy participants aged 20-63 were enrolled in this randomized, placebo-controlled, double-blind study. Participants were randomly assigned to LLF group, (LF 270 mg╱day)or placebo group(n=30, respectively). Results The IgA secretion were greater in LLF group than those of placebo group(P<0.05). No significant differences were found in defecation frequency and fecal output between two groups. Some indices related to enteric environment such as fecal microbiota and putrefactive products were beneficially changed only in LLF group. Improving of sleep quality and reducing fatigue feeling is also confirmed in LLF group. Salivary secretory IgA secretion was positively correlated with defecation frequency and output, negatively correlated with fecal phenol in LLF group. In addition, no clinically relevant adverse events were observed during the test period.Conclusion These findings suggest that LF supplementation could increase IgA secretion and improve the enteric environment, sleep quality and daily mood.
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BRIEF COMMUNICATION
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凍り豆腐の長期摂取による糖尿病予防・改善効果
44巻9号(2016);View Description Hide DescriptionWe researched that intake of Kori-tofu have an effect on carbohydrate metabolism. Eight healthy but have high normal serum HbA1c subjects ingested 16.5 g of seasoned Kori-tofu per day for 12 weeks. Serum HbA1c and other biomarkers were measured. In the result, intake of the Kori-tofu decreased serum HbA1c level significantly. The findings indicate intake of Kori-tofu improve carbohydrate metabolism, that prevent diabetes.
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INFORMATION
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CONSORT 2010 声明-ランダム化並行群間比較試験報告のための最新版ガイドライン-(薬理と治療2010;38:939-49. より再掲載)
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