薬理と治療
Volume 44, Issue 2, 2016
Volumes & issues:
-
扉・目次
-
-
-
TOPIC 第15回CRCと臨床試験のあり方を考える会議 2015 in KOBE
-
- 受賞演題
-
-
-
-
Global Project REPORT
-
-
アカデミア主導国際共同臨床試験の推進プロジェクト− OECD によるグローバルヘルスリサーチイニシアチブ−
44巻2号(2016);View Description Hide Description
-
-
ORIGINAL ARTICLES
-
-
慢性閉塞性肺疾患の気道閉塞性障害に伴う諸症状の緩解を目的にオーキシス(R) 9μg タービュヘイラー(R) を使用した場合の安全性の検討―オーキシス(R) 9μg タービュヘイラー(R) 使用成績調査結果―
44巻2号(2016);View Description Hide Description目的オーキシス(R)9μg タービュヘイラー(R)(ホルモテロールフマル酸塩水和物吸入剤)の製造販売後のCOPD の長期管理薬としての使用実態下における副作用の発現状況を確認するため,本剤をはじめて使用するCOPD 患者を対象に使用成績調査を実施した。方法内科,呼吸器科を中心とした全国の医療機関の患者をプロスペクティブな中央登録方式で登録し,観察期間は12 週間とした。本剤の投与開始時の患者背景,観察期間中の投与状況,副作用・感染症および重篤な有害事象の種類別発現状況,β2刺激薬の薬理作用に関連すると考えられる副作用,重篤な心血管系有害事象,COPD 増悪発現例について調査した。結果安全性解析対象症例369 例中,副作用は11 例(3.0%),13 件に認められた。副作用の内訳は食欲減退および悪心の各2 例,咽頭炎,高カリウム血症,味覚異常,不安定狭心症,不整脈,動悸,喉頭不快感,倦怠感および口渇の各1 例であり,食欲減退および不安定狭心症の各1 例以外はいずれも非重篤な副作用であった。重篤な有害事象は9 例(2.4%),18 件に認められたが,食欲減退および不安定狭心症の各1 例を除いて因果関係は否定された。β2刺激薬の薬理作用に関連すると考えられる副作用として非重篤な不整脈および動悸の各1 例(0.3%),重篤な心血管系有害事象として不安定狭心症および心筋梗塞の各1 例(0.3%)が報告された。COPD 増悪例は1 例(0.3%)で報告されたが,転帰は回復であった。結論オーキシス(R) 9μg タービュヘイラー(R) の使用実態下での使用成績調査において,副作用発現率は承認時までの臨床試験とほぼ同程度であり,重篤な副作用や有害事象,β2刺激薬の薬理作用に関連すると考えられる副作用,重篤な心血管系有害事象およびCOPD 増悪例は少なく,特記すべき問題点は認められなかった。【利益相反】本調査はMeiji Seika ファルマ㈱へ委託のもと,アストラゼネカ㈱が実施した使用成績調査(Clinical Trials.gov 登録番号:NCT01749462)で,本剤は今後再審査申請を行います。本稿の作成には,アストラゼネカ㈱の資金提供によりELMCOMTM/Elsevier Japan K. K. が関与しました。【謝辞】本調査にご協力いただきました医師の方々ならびに関係者の皆さまに深謝いたします。 -
BPSD モデル(チアミン欠乏)ラットにおける精神神経症状および消化器症状に対する抑肝散と抑肝散加陳皮半夏の効果
44巻2号(2016);View Description Hide Description本稿で著者らは,抑肝散および抑肝散に陳皮と半夏が加味された抑肝散加陳皮半夏の薬理作用解明の一環として,認知機能障害に加えBPSD(behavioraland psychological symptoms of dementia)様症状を示す動物モデルとして,慢性的にチアミン(ビタミンB1)を欠乏させた(TD)ラットを用い,TD により誘発される攻撃性行動や記憶障害などの精神神経症状および摂餌量低下や胃排出能低下,糞便減少などの消化器症状に対する両漢方薬の効果を比較検討した。レジデント・イントルーダー試験により攻撃性行動を評価したところ,抑肝散および抑肝散加陳皮半夏はTD ラットが呈する攻撃性行動の増加を抑制した。また,ステップ・スルー型受動回避課題にて記憶保持能を検討したところ,両漢方薬はTD による記憶保持能の低下を改善した。さらに,記憶保持能力改善作用の機序として,海馬歯状回における神経新生に与える影響を検討したところ,両漢方薬はTD による海馬歯状回顆粒細胞下帯におけるBrdU陽性細胞数の低下を改善した。消化器症状に関しても,両漢方薬はTD による体重および摂餌量の低下を改善した。さらに,両漢方薬はTD ラットで認められた胃排出遅延や糞便量の低下に対して改善傾向を示した。すべての薬効において,両漢方薬間に有意差は認められなかった。以上の結果から,抑肝散と抑肝散加陳皮半夏はTD ラットが呈する精神神経症状および消化器症状を同程度改善することが明らかとなった。抑肝散加陳皮半夏も抑肝散と同様に,消化器症状を伴う認知症の周辺症状に有効な薬剤である可能性が示唆された。 -
鶏冠由来ヒアルロン酸含有加工食品の膝関節の自覚症状に対する長期摂取時の有効性および安全性の評価―プラセボ対照ランダム化二重盲検並行群間比較試験―
44巻2号(2016);View Description Hide DescriptionObjectives The aim of this study was to evaluate the effect and safety of a dietary supplement (Kojun premium(R))containing hyaluronic acid derived from chicken combs on knee pain, stiffness and discomfort. Methods We conducted a randomized, double-blind, placebo-controlled, parallel-group comparison study. The subjects, 80 adults whose Kellgren-Lawrence classification of osteoarthritis of the knee corresponded to 0-Ⅱ and who were not suffering from the disease, were randomly divided into two groups: the test product(chicken comb extract-containing supplement) group and the control product(placebo)group. Knee pain and discomfort were evaluated using a visual analogue scale(VAS). The subjects were given each product for 12 weeks. Blood and urine samples were tested to evaluate the safety of the test product. Results Significant positive results demonstrating the effectiveness of the chicken comb extract-containing supplement appeared 4︱12 weeks after the intake as demonstrated by the VAS scores. The blood test results did not indicate any health hazard from the use of these supplements. Conclusion These results indicate that an intake of hyaluronic acid-containing supplements derived from chicken combs is safe and effective in managing knee pain, stiffness and discomfort. -
Inhibition of Melanin Synthesis and Skin Whitening Effect by Heat—induced Yeast Extract(Cerepron(R))
44巻2号(2016);View Description Hide DescriptionObjectives The aim of this study is to investigate the effect of a newly developed heat-induced yeast extract(Cerepron(R))on melanin synthesis and on human skin whitening. Methods The heat-induced yeast extract(Cerepron(R))was added to mouse melanoma B16 cells, and the inhibitory effect on melanin synthesis was evaluated. To elucidate its inhibitory mechanism on melanogenesis, tyrosinase assay and quantitative real-time RT-PCR for tyrosinase gene expression were carried out. Then, the skin whitening effect of the yeast extract was evaluated in a clinical trial. Results The heat-induced yeast extract inhibited melanin synthesis in a concentration-dependent manner (1-5 mg╱mL). The yeast extract did not inhibit the enzymatic activity of mushroom-derived tyrosinase up to 2 mg╱mL, but did suppress the expression of tyrosinase mRNA in a concentration-dependent manner (1-5 mg╱mL). In the clinical trial, the daily intake of 100 mg of the yeast extract for 8 weeks exhibited significant skin whitening effect. Conclusions The newly-developed heat-induced yeast extract (Cerepron(R))has inhibitory effect on melanin synthesis by suppressing tyrosinase gene expression, which leads to human skin whitening effect. Therefore, Cerepron(R) as a promising skin whitening material can serve both for cosmetic and dietary supplements. -
運動中の分岐鎖アミノ酸(BCAA)とクエン酸摂取による疲労軽減効果
44巻2号(2016);View Description Hide DescriptionFor players to exert their maximum athletic performance, it is crucial for them to recover promptly from exhausted status caused by exercise, and to regain appropriate physical condition. It has been reported that BCAA(branched-chain amino acids)and citric acid have fatigue-reducing effect for athletes. Based on this report, this research was conducted to explore the possibility of the synergistic fatigue-reducing effect of citric acid and BCAA on exhausted athletes. Forty-four American football players were divided into three groups, and each group was administered BCAA, both citric acid and BCAA, and placebo, in double-blinded manner. The interventional examination was conducted from May 15, 2012 to May 17, and the each group member was applied 120%- strength exercise, compared with the normal training, for 3 and 5 hours╱day. Blood sample were collected from the players 3 weeks prior to, and a day after the examination, and the serum level of CPK activity was compared. Muscle fatigue Test(VAS) and mental fatigue Test (CR-10)Tests were also conducted during the examination to estimate the subjective fatigue level of the players. The blood CPK level which is indicator of muscle injury, increased in all players after the exercise. In addition, the CPK level in citric acid+BCAA group, showed significant lower than that in placebo group(P<0.05). In the CR-10 Test, the mental fatigue level of subject was shown to be lower in citric acid+BCAA group compared with placebo group. These data indicate that simultaneous intake of citric acid and BCAA contribute to the reduction of fatigue caused by exercise. -
血中トリグリセリド濃度が正常かまたは軽度上昇している日本人中高年者における精製魚油含有食品の血中トリグリセリド,血圧および認知機能に及ぼす効果―無作為化,二重盲検,プラセボ対照,並行群間比較試験―
44巻2号(2016);View Description Hide DescriptionObjective Hypertriglyceridemia or elevated blood levels of triglycerides(TG)is a leading risk factor for developing atherosclerotic cardiovascular diseases. A randomized, double-blind, placebo-controlled, 12 week, parallel-group trial was designed primarily to investigate the effects of purified fish oil-containing capsular diet(FO diet)on serum TG in middle-aged Japanese men and women with normal or mildly high serum TG. Besides, as fish oil and its principal bioactive ingredients n-3 polyunsaturated fatty acids(mainly DHA and EPA)have been claimed to improve blood pressure and cognitive function, the effects of FO diet on blood pressure and a certain aspect of cognition were also assessed. Methods Sixty-six subjects were allocated at random to receive either FO diet containing 603.2 mg n-3 fatty acids (544 mg DHA and 59.2 mg EPA)or placebo once daily for 12 weeks. Assessments were carried out at baseline and after 4, 8 and 12 weeks of intervention for serum TG and at baseline and after 12 weeks of intervention for blood pressure, as well as for cognitive function, by the use of Stroop test. The efficacies of FO diet intake were evaluated by comparing the change from baseline between the FO diet and placebo groups. Results The FO diet significantly lowered serum TG subsequent to 8 and 12 weeks of sup-plementation. No significant modification of both systolic and diastolic blood pressures was seen after the 12-week supplementation with the FO diet, although the sub-group analysis showed that supplementation with the FO diet significantly lowered the systolic blood pressure in subjects with normal-high and mildly hypertensive systolic blood pressures(130-159 mmHg). The FO diet was not found to improve significantly the over-all results of the Stroop test, except one of eight outcome parameters of the test(the number of incorrect answer on the Subscale 3)that was improved to a significant level. No untoward side effect nor laboratory abnormality was observed in both groups throughout the 12-week intervention period. Conclusions The FO diet may have benefits in lowering a risk for developing atherosclerotic diseases mainly through reducing serum TG in middle-aged Japanese men and women with normal or slightly high serum TG. -
Long—term Intake of Glucosylceramide Extracted from Pineapple―Safety Evaluation in Healthy Adults―
44巻2号(2016);View Description Hide DescriptionObjective The objective of this study was to investigate the safety of long-term oral intake of glucosylceramide extracted from pineapple(PGC: 1.2 mg╱day)in healthy volunteers. Methods A double-blind randomized controlled study was conducted in 48 healthy volunteers (24 males, 24 females)to evaluate the safety of long-term PGC intake. Volunteers were randomly assigned to two groups and given either 1.2 mg╱day of PGC or placebo for 12 weeks. Body weight, body mass index (BMI), body fat percentage, blood pressure, heart rate, blood parameters, urine parameters, and subjective symptoms were recorded throughout the study. Results No clinically concerning changes in body weight, BMI, body fat percentage, blood pressure, heart rate, blood parameters, and urine parameters were found throughout the study. Conclusions The results indicated that PGC was safe for consumption in the healthy volunteers. -
Excessive Intake of Glucosylceramide Extracted from Pineapple―Safety Evaluation in Healthy Adults―
44巻2号(2016);View Description Hide DescriptionObjective We aimed to investigate the safety of excessive intake of glucosylceramide extracted from pineapple(PGC: 6.0 mg╱day)in healthy adult volunteers. Methods Twenty-two healthy volunteers(10 males, 12 females; mean age, 44.1±13.0 years) were given five tablets containing PGC(1.2 mg╱tab)daily for 4 weeks. Body weight, body mass index(BMI), body fat percentage, blood pressure(BP)and heart rate(HR), blood and urine parameters, and subjective symptoms were recorded throughout the study. Results No clinically significant changes in body weight, BMI, body fat percentage, BP, HR, and blood and urine parameters were found throughout the study. Conclusions The present study indicated that the excessive intake of PGC(6.0 mg╱day for 4 weeks)was found to be safe in healthy Japanese volunteers. -
難消化性デキストリン含有茶飲料摂取による食後血中中性脂肪上昇抑制―無作為化プラセボ対照二重盲検クロスオーバー試験―
44巻2号(2016);View Description Hide DescriptionObjective The aim of this study was to evaluate the effectiveness of indigestible dextrin-containing tea beverage on the postprandial increase in serum triglyceride level in subjects with moderately high fasting serum triglyceride levels. Methods Volunteers(79 subjects)with their fasting serum triglyceride levels of 120-199 mg╱dL were enrolled in a randomized, placebo-controlled, double-blind, crossover study. Subjects ingested a high-fat meal(44.3 g fat)together with either a test beverage containing 5 g(as dietary fiber)of indigestible dextrin or a placebo beverage without indigestible dextrin. Serum lipids were determined before and 2, 3, 4, and 6 hours after the high-fat meal ingestion. Results When the subjects ingested test beverage, postprandial increases in the levels of serum triglyceride and remnant-like lipoprotein particle cholesterol(RLP-cholesterol)were low compared to those when the subjects ingested placebo beverage. The area under the curve (AUC)for serum triglyceride levels was 1504±478 mg・h╱dL for test beverage and 1593±509 mg・h╱dL for placebo; P=0.044 and the AUC for serum RLP-cholesterol was 83.8±26.8 mg・h╱dL for test beverage and 89.6±29.5 mg・h╱dL for placebo; P=0.038. Conclusions The ingestion of indigestible dextrin-containing tea beverage suppresses the increase in the postprandial serum triglyceride and remnant︱like lipoprotein particle cholesterol levels in subjects with moderately high fasting serum triglyceride levels. -
難消化性デキストリン含有茶飲料摂取の食後血糖値上昇抑制効果―無作為化プラセボ対照二重盲検クロスオーバー試験―
44巻2号(2016);View Description Hide DescriptionObjectives The aim of this study was to evaluate the effectiveness of indigestible dextrin-containing tea beverage on the postprandial increase in blood glucose level in subjects with relatively higher postprandial blood glucose levels in a randomized, placebo-controlled, double-blind, crossover study. Methods The trial was conducted with 60 Japanese subjects with fasting glucose levels less than 126 mg╱dL and a 30-min postprandial blood glucose level ranging 140-199 mg╱dL. Subjects consumed either a test beverage containing 5 g(as dietary fiber)of indigestible dextrin or a placebo beverage without indigestible dextrin together with a high carbohydrate meal, and the levels of blood glucose and insulin were determined before and 30-120 min after the meal. Results When the subjects ingested test beverage, postprandial increase in the level of blood glucose was low compared to that when the subjects ingested placebo beverage. The area under the curve(AUC)for blood glucose levels was 288.6±43.4 mg・h╱dL for test beverage and 299.6±37.1 mg・h╱dL for placebo; P=0.048, and the maximum blood glucose level between 0 and 120 min following the test meal was 171.8±27.1 mg╱dL for test beverage and 178.8± 24.5 mg╱dL for placebo(P=0.035). There was no serious adverse event related to the ingestion of test beverage. Conclusions Our findings suggest that the consumption of test beverage containing 5 g(as dietary fiber)of indigestible dextrin suppresses postprandial increase in blood glucose level in subjects with relatively higher fasting blood glucose levels.
-
-
INFORMATION
-
-