薬理と治療

Background Although various factors are considered while assessing the pathogenesis of gastroesophageal reflux disease（GERD）, it has been well known that increased gastric acid secretion, reflux, and esophageal clearance dysfunction are particularly important onset mechanisms. Rikkunshito is a Japanese traditional medicine widely prescribed for the various symptoms of GERD. In the current study, we examined salivary secretion as a possible mechanism of rikkunshito administration for the symptoms of GERD. Methods Rikkunshito（250 and 500 mg╱kg）was intraduodenally administered to normal and GERD model rats. The oral fluid was collected using a cotton ball placed in the oral cavity at an interval of every 30 min after rikkunshito administration. The amount of fluid was assessed by the change in the weight of the cotton ball, and the pH of the fluid was also measured. Results Rikkunshito increased the oral fluid weight in normal rats. GERD model rats exhibited a decreased in the pH of the oral fluid, which may be closely related to the reflux of gastric acid. Rikkunshito administration suppressed the decrease in pH and increased the oral fluid weight in GERD model rats. Conclusion It is conceivable that rikkunshito inhibits the pH decrease of the oral fluid in GERD model rats via increase in salivary secretion. Our findings support the possibility that increased salivary secretion may be the one of the action mechanisms for beneficial effects of rikkunshito on some symptoms of GERD patients.

In earlier reports, we developed a novel amino acid（AA）mixture comprised of arginine, alanine, and phenylalanine（A-mix）, and suggested that pre-exercise ingestion of A-mix increases levels of blood ketone bodies and glycerol both during exercise（Ex）and following a bout of Ex by increasing secretion of adrenalin and glucagon. However, it is unclear whether this acute response induced by ingestion of A-mix combined with Ex is sustained if the supplement is ingested for several weeks. Herein, we explored the long-term effects of A-mix with Ex on the development of obesity in C57BL╱6 mice that were fed a high-fat diet （HF）. We compared the effects over a 5-week period utilizing treadmill-running Ex with or without A-mix（1 g╱kg╱day）supplementation. We found that HF＋A-mix suppressed HF-induced bodyweight gain by 19％, and found that the weight of mesenteric fat was significantly reduced in the group that received the A-mix supplement. Moreover, levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha（PGC1-α）in brown adipose tissue（BAT）were significantly increased in the HF＋A-mix group. Taken together, these results suggest that dietary A-mix supplementation, in combination with continuous Ex, attenuates diet-induced obesity by modulating levels of PGC1-α in BAT, which is involved in mitochondrial biogenesis and function.

Objective The aim of this study was to evaluate the effects of intake of heat-killed Lactobacillus casei subsp. casei 327（327 strain）on young womenʼs skin conditions. Methods A randomized, double-blind, placebo-controlled, parallel-group study was conducted for 60 young women. The volunteers were administered test food containing 50 mg （approximately 1*10 11 bacteria）of heat-killed 327 strain or placebo food for 6 weeks. The levels of stratum corneum hydration and transepidermal water loss（TEWL）and score of skin surface texture were measured at the right cheek. Results Data of 54 subjects（n＝27 each）were obtained and analyzed. No clear statistically significant differences were observed in both groups. But TEWL of 327 strain intake group showed a lower tendency than that of placebo food group. In analysis subcategory with high level of TEWL, the TEWL of 327 strain intake group（n＝10）was significantly lower than that of placebo food group（n＝14）at 4 weeks. Conclusions Intake of 327 strain seems to have a skin dryness inhibiting effect.

Objectives To evaluate the effect of tablets containing lactononadecapeptide （NIPPLTQTPVVVPPFLQPE） on cognitive function in healthy middle-aged and senior adults. Methods We conducted a randomized, double-blind, placebo-controlled trial in 72 healthy Japanese subjects. Subjects were randomly divided into test and placebo groups before ingesting 2.1 mg╱day lactononadecapeptide or the equivalent in placebo tablets for 12 weeks. Cognitive function and quality of life（QOL）were measured using the Mini-Mental State Examination（MMSE）, the Uchida-Kraepelin test, the recognition memory test and SF-36, at baseline and after 12 weeks of supplementation. Results Changes in the number of correct answers on the Uchida-Kraepelin test from baseline to 12 weeks were significantly different between the test and placebo groups. There were a statistically significant improvement in the social functioning, vitality and mental component summary of the SF-36 after 12 weeks intake of lactononadecapeptide tablets. There were no significant improvement in these scores in the placebo group. There were no adverse events attributed to lactononadecpeptide tablets, and no marked changes were observed in the blood and urinary analysis. Conclusion Supplementation of healthy middle-aged and senior adults with lactononadecapeptide tablets for 12 weeks improved cognitive abilities, including attention and speed of information processing.

目的アサヒビール社が有するビール酵母Saccharomycespastorianus より製造した細胞壁（ビール酵母細胞壁SP-1，以下SP-1 と略す）の保健機能を評価するため，疲労感が強く，NK 細胞活性が低値の男性勤労者を対象とした無作為化プラセボ対照二重盲検並行群間比較試験を実施した。方法日中に事務作業に従事する40～60 歳の男性を対象にスクリーニングを行い，調査票Profile ofMood States（POMS）短縮版の疲労スコアが60 以上，かつNK 細胞活性が低値の者を被験者として選定した。試験はプラセボ群，SP-1 低用量群，およびSP-1 高用量群の3 群を設け，1 群15 名の計45 名とした。低用量群は，錠剤化したSP-1 を1 日1500mg，高用量群は1 日3000 mg をそれぞれ8 週間継続摂取させた。なお，プラセボ群はデキストリンを1500 mg 同様に摂取させた。試験開始時，4 週間後，および8 週間後に採血，および各種調査票によるアンケートを実施し，疲労感，各種免疫マーカーの変動を調査した。結果SP-1 摂取群で試験開始時と比較して調査票POMS短縮版における疲労スコアの有意な改善が認められた。この疲労感軽減効果は職業性ストレス簡易調査票でも同様に確認された。血液中の各種免疫マーカーでは，試験開始8 週間後の白血球中NK 細胞率・数を試験開始時からの変化量で群間比較したところ，NK 細胞率はSP-1 両群で，NK 細胞数はSP-1 高用量群でプラセボ群に対して有意に高値を示した。一方，好中球の貪食活性・呼吸バースト，NK 細胞活性，リンパ球の幼若化能においては，SP-1 摂取による変化は認められなかった。なお，試験期間を通じて，低用量群，高用量群ともにSP-1 摂取による異常は認められず，安全性を確認した。結論これらの結果から，SP-1 を継続摂取することで，勤労者の疲労感を軽減するとともに，白血球中のNK 細胞数を増加させることが示唆された。【利益相反】本研究はアサヒグループホールディングス㈱の資金提供を受けて実施された。著者のうち，指原浩一，前川祥太郎，水谷由布，小谷哲司，田頭素行，中村康則はアサヒグループホールディングス㈱の従業員である。

Background Chicken collagen hydrolysate（2.9 g daily）has been reported to have a hypotensive effect and to improve brachial-ankle pulse wave velocity（baPWV）, an indicator of arterial stiffness, in subjects with high-normal blood pressure or stageⅠ hypertension. Objective The aim of this randomized, double-blind, parallel-group, placebo-controlled study was to evaluate the dose-related effects of a food containing chicken collagen hydrolysate on blood pressure and vascular endothelial function. Methods/study design A total of 75 volunteers with high-normal blood pressure（systolic blood pressure［SBP］130-139 mmHg╱diastolic blood pressure［DBP］85-89 mmHg）or stageⅠ hypertension（SBP 140 -159 mmHg╱DBP 90-99 mmHg）were randomly allocated to 3 groups receiving either a placebo（group P）, low-dose（1.7 g daily）chicken collagen hydrolysate（group L）, or high-dose（2.9 g daily）chicken collagen hydrolysate（group H）. The period of intake was 12 weeks. Blood pressure was evaluated and vascular endothelial function was measured by flow︱mediated dilatation（FMD）. Results Consumption of chicken collagen hydrolysate vs. placebo significantly improved blood pressure, but not FMD. Change in SBP was significantly lower at the 8th week in the L group（－5.20±8.93 mmHg）and 12th week（－5.69±13.20 mmHg）than in the placebo group（＋1.32±7.96 mmHg and ＋2.08±11.33 mmHg, respectively）（P＜0.01 and P＜0.05, respectively）and significantly lower at the 8th week in the H group（－4.90±11.97 mmHg） than in the placebo group（P＜0.05）. No serious adverse event was observed during this study. Conclusion These results indicate that daily intake of 1.7-2.9 g of chicken collagen hydrolysate benefits persons with high-normal blood pressure or stageⅠ hypertension.

背景　腸溶性製剤は，有効成分を胃内で放出させず，小腸内で放出するように設計された製剤であり，有効成分が胃で分解されるのを防ぎ，また胃に対しての刺激を低減するなどの目的で利用される。三生医薬㈱は，ソフトカプセルの皮膜に腸溶性の機能を付与した『E-カプセルクリア（ノンコート）』（E-カプセル）を開発した。これはコーティング不要の腸溶性製剤である。　目的　このE-カプセルが，設計どおりに胃では溶けず，小腸で溶解することをヒトの体内で直接的に観察することで，腸溶性製剤としての機能を実証する。　方法　開発した腸溶性カプセルに硫酸バリウムを充填し，摂取後の経時的なX 線撮影によってカプセルのヒト体内における挙動を観察した。　結果　腸溶性カプセルを摂取した被験者全員において，胃での溶解はみられず，摂取後40 分から80 分後に小腸での溶解が確認された。　結論　E-カプセルはヒト体内においても腸溶性としての機能性を有することが実証された。【COI】本試験は，三生医薬㈱が㈱TTC に委託し実施した。委託の際に試験に使用した試験カプセルと試験実施費用を㈱TTC に提供した。

BARLEYmax の摂取量として12 g╱day に設計した食品（ショートバー形態）の経口摂取が睡眠改善に及ぼす影響を検討するために，不眠に悩みのある日本人女性21 名（36.59±4.45 歳）を被験者として試験を開始し，体調不良とアンケート記載漏れにより最終的には18 名のデータで解析を行った。本試験は，摂取期間4 週間で摂取前後比較法にて実施した結果，BARLEYmax の摂取量として12 g╱day で，睡眠改善において効果が確認された。本試験結果よりBARLEYmaxの摂取は，不眠に悩みのある成人女性に対する睡眠改善効果が示唆された。

Objectives This study elucidated the effects of food containing Euglena gracilis on improvement in constipation. Methods This open study included 20 healthy adult volunteers（females, n＝20, 20︱60 years） who consumed a placebo or test food（low dose, medium dose, high dose）for 8 weeks. For the main evaluation items, defecation frequency, defecation days, excretion amount are used. We examined times per day for stool frequency. The defecation days counted the number of days during which one week defecation occurred. For the secondary evaluation, the shape of the stool, color of the stool, smell of feces, sensation after defecation were used. In addition, when defecation occurred more than once a day, the above contents were investigated at each defecation. Results The number of defecation days and defecation frequency in test food group were significantly different to those in the placebo group after 8 weeks of intake. In the other hand, no fluctuation due to intake of the test meal was observed in the feces shape, the color of the stool, the smell of feces, and the sensation after defecation. Conclusions Food containing Euglena gracilis can suppress on improvement in constipation.

Objectives A randomized, double-blind, placebo-controlled, cross-over study was conducted to evaluate the effects of food containing Terminalia bellirica extract on postprandial blood glucose levels. Methods Forty-eight volunteer subjects with borderline diabetes were selected. These subjects had fasting blood glucose levels between 110 and 125 mg╱dL or 2-hour glucose values between 140 and 199 mg╱dL in a 75︱g oral glucose tolerance test. The subjects were randomly divided into two groups who ingested either test food containing Terminalia bellirica extract （containing 20.8 mg gallic acid）or a placebo food, before ingesting the loading diet. Blood glucose levels were measured before and 30, 60, 90, and 120 minutes after ingestion. Results Compared to placebo food, the test food showed significantly decreased postprandial blood glucose areas under the curve after the loading diet was ingested（P＜0.05）. In addition, a decrease was also observed in the blood glucose levels measured 30 and 60 minutes after ingestion（P＜0.1）. During this study period, no abnormal changes were observed that were attributed to the test food. Conclusions These results indicated that ingesting food containing Terminalia bellirica extract before a meal has an inhibitory effect on elevation of postprandial blood glucose levels.