薬理と治療

Objective　There is currently insufficient guidance regarding how to deal with sick days in patients with diabetes. The purpose of this study was to evaluate the usefulness of drug-administration guidance using a Sick-day Manual. Methods　We obtained consent from 40 patients who were admitted for diabetes education. The patients confirmed their understanding of and completed a questionnaire survey twice: once at the time of admission and once at discharge. Results　The degree of interest in and understanding of sick days increased significantly. In the overall evaluation, a score of 4 or 5 accounted for 86.5％ of the outcomes. As a result of the customer satisfaction analysis, the importance and satisfaction of the instruction regarding the medicine adjustment method on sick days were the highest. Conclusion　These results indicate that we were able to establish a high degree of satisfaction regarding sick day education and to develop drug-administration guidance that significantly increased the degree of interest in, and the understanding of, sick days. （UMIN000036247）

SUPREP® is a sulfate-based bowel cleaning solution for preparation of colonoscopy developed in the United States, has been marketed widely in US, Europe and other regions. However, SUPREP® is not currently marketed in Japan. In this study, we imported and used SUPREP® for NPF-08 to assess the safety and efficacy in Japanese healthy adult male subjects. This study consisted of 4 steps. In Steps 1 to 3, to assess safety and pharmacokinetics of sulfate ion, 50 subjects were administered from 480 mL up to 960 mL of NPF-08 and a double volume of water in one day（Same-day dose regimen）or 480 mL of NPF︱08 and 960 mL of water on the first day and up to 480 mL of NPF︱08 and a double volume of water on the second day（Two-day split-dose regimen）. In Step 4, to assess safety, 40 subjects were administered under Same-day dose regimen on the day of colonoscopy or under Two-day split-dose regimen until the stool becomes clear. To assess the bowel cleaning efficacy, the subjects underwent colonoscopy. There were no serious adverse events, and all subjects completed the study drug administration except one who had vomiting. The subject who had vomiting dropped out but recovered immediately without treatment. No abnormalities in the pharmacokinetics and no accumulation of sulfate ions were observed. The bowel cleansing efficacy rate was 100.0％（40/40）on both Same-day dose regimen and Two-day split-dose regimen. Based on the above results, NPF-08 is a safe and useful bowel cleaning preparation for colonoscopy. （ClinicalTrials.gov Identifer：NCT03423771）

Objectives　The objective of the present study was to compare the pharmacokinetics of compound comprising Isoquercitrin included by γ-Cyclodextrin（C-IQC-CD）, and the physically mixed quercetin and dextrin（C-QD）in healthy adult male subjects. Methods　Healthy male volunteers（8 subjects）aged between 22 to 51 years were performed in a non-randomized, double-blind, crossover controlled study, and ingested 1.1 g of C-IQC-CD（i. e. 220 mg Isoquercitrin）or 1.1 g of C-QD（i. e. 143 mg quercetin）with 100 mL water. Blood samples were collected at 0, 0.5,1 , 2, 3, 6, 8, and 24 h after the supplementations. Results　In this crossover study, the overall kinetic behavior of total quercetin metabolites differed remarkably after the ingestion of either C-IQC-CD or C-QD. The area under the curve （AUC）of plasma concentration from 0 to 3 h of C-IQC-CD（15.92±2.15μM・h）was more than 48 times higher compared to C-QD（0.33±0.11μM・h）. and AUC0-24 of C-IQC-CD （36.81±4.3μM・h）was more than 10 times higher compared to C-QD（3.47±1.12μM・h）. Also, the Cmax of C-IQC-CD（10.19±1.52μM）was found about 29 times higher than C-QD （0.35±0.07μM）.Conclusion　Compound comprising Isoquercitrin included by γ-Cyclodextrin（C-IQC-CD） with improved solubility of Isoquercitrin showed a dramatically higher bioavailability than physically mixed quercetin and dextrin（C-QD）. It implies that C-IQC-CD could have the ability to show various biological effects on human health. Their results could be applied to functional foods health supplements, and complementary and alternative medicines after further investigations（. UMIN ID: UMIN000038580）

Objectives　To evaluate the therapeutic potentials of a salt resistance plant-derived lactic bacterium（SR-PDLB）against mild symptoms of anemia, we designed a randomized double-blind placebo-controlled methodology and discussed the clinical efficacy/safety of the SR-PDLB-containing functional food. Methods　Forty female healthy participants ranging in age from 28 to 55（three subjects in their 20 s, seven subjects in their 30 s, twenty-one subjects in their 40 s, and nine subjects in their 50 s）took part in our clinical trial equipped with the above-mentioned methodology. We divided them into two groups（n＝20）：placebo-control group（mean age±SD：43.5±7.9） and test group（mean age±SD：43.6±6.9）. As the test food, a round tablet（0.3 g）containing Tetragenococcus halophilus［a lactic acid bacterium KURAHANA, strain no. LTK-1］（5.0×1011 cells, 0.125 g）and dextrin（0.117 g）was used for oral ingestion of the tablet to the test subjects, two drops a day（total：0.6 g test food）for 12 weeks. On the other hand, the control experiment was performed in the same manner（total：0.6 g placebo）, except ingesting a colorized round tablet（0.3 g）containing approximately twice the amount of dextrin（0.239 g）and a caramel colorant（6.0 mg）. As a proof-of-concept proposal, we investigated the effects of the test food on measurements of our primary╱secondary endpoints for anemia therapy. Results　According to the overall result of the primary ╱ secondary endpoints, it was pretty obvious that the test︱food intake revealed outstanding increases in both Hb and Ht values, as contrasted to the placebo control. But as a point worthy of special mention, the subjectsʼ feelings to their skin conditions in the test group were significantly greater, depending on the questionnaire scores about their subjective symptoms for anemia. That is why we have great concern that the improvement of skin condition might be caused by consuming the test-food for a prospective effective blood flow, regardless of whether the anemia is iron-deficiency or pernicious. Conclusions　All through this trial, we keenly realized again the importance of consuming the functional KURAHANA from miso in a symbiotic manner. Our experimental results support the fact that daily ingestion of SR-PDLB-containing functional foods can reveal a kind of anti-anemia action, taking advantage of significant increases in Hb concentration, Ht volume, and so on（. UMIN ID: UMIN000037688）

Background　Human face plays important roles in the identification and communication. Face changes with age, and the wrinkles around eyes are common age-related symptoms. In this study, we examined the effect of a face wash containing placenta extracts, which has anti-inflammatory and whitening effects, on these facial wrinkles. Methods　The study was carried out with 15 healthy female subjects with age ranging between 30 and 59 years. They used White Clay Savon Mask, containing placenta extracts （provided by Mʼz Science Corporation, Fukuoka, Japan）, only to one side of their faces twice a day for 4 weeks. Both sides of their faces were taken by the photo, and the wrinkles were evaluated by a single blind method, judged by the special inspectors according to the wrinkle grade established by Japanese Cosmetic Science Society. Skin condition of both side of their faces was also examined by the questionnaire. Results　The wrinkles only on the side of the faces using the face wash containing placenta extracts were significantly improved from the judgement by the special inspectors, while no significant changes were recognized on the other side of the faces. Statistical comparison of the changes in the wrinkle grade between the two sides of the faces also supports the improvement of the wrinkles around eyes by using the face wash. Moreover, result of the questionnaire indicated that almost all the subjects of this experiment realized the improvement effects in the skin condition, such as clarity, moisture, softness, and gloss. Conclusions　Significant effects of a face wash containing placenta extracts on the facial wrinkles around eyes and the improvement in the skin condition were statistically confirmed from the study. We assume that various bioactive substrates contained in placenta extracts are responsible for these antiaging effects on the skin（. UMIN ID: UMIN000039283）

Objectives　The objective of this study was to investigate the effect of shark liver oil vs vitamin C diet on infectious diseases of influenza virus. Methods　An assigned alternately was conducted in 110 subjects. They were assigned to 2 groups and received either shark liver oil containing 500 mg or vitamin C 990 mg from the start of the test ingested every day. The efficacies were evaluated by analyzing influenza morbidity comparing the change between the test period shark liver oil and vitamin C groups. Results　The shark liver oil groups significantly lowered influenza morbidity（. χ2＝41509, P＜0.05）Next, in the subject（n＝55）with influenza vaccine ingestors, there were none in shark liver oil group and 3 people in vitamin C group. Conclusions　The shark liver oil containing diet may have benefits in lower infectious diseases of influenza virus morbidity.

Objective　The aim of this study is to clarify the effects of β-carotene on the nasal symptoms of perennial allergic rhinitis（PAR）in subjects without seasonal allergic rhinitis（SAR）symptoms. Methods　We conducted a randomized, double-blind, placebo-controlled, parallel-group comparative study in ninety-six subjects with mild to moderate PAR symptoms, but without SAR symptoms. They were randomly divided into two groups and ingested a mixed vegetable and fruit juice containing β-carotene（β-carotene group）or a placebo juice（placebo group） for 8 weeks. The symptoms of PAR were assessed by classification of the severity of allergic rhinitis symptoms（CSARS）and Japanese allergic rhinitis standard quality of life questionnaire （JRQLQ）. The serum concentrations of β-carotene, vitamin A （retinol）and IgE which was reported to be suppressed by vitamin A were measured. Results　The changes of“sneezing”and“nasal symptoms”in CSARS at week 2, and the change of“sneezing”in JRQLQ symptoms scores at week 8 were significantly larger in β-carotene group than in placebo group. In QOL scores of JRQLQ, “ social life”and “sleep”scores at week 8 were significantly lower in β-carotene group than in placebo group. The serum concentration of β-carotene at week 4 and 8 were significantly higher in β-carotene group than in placebo group. On the other hand, there were no significant differences in the serum concentration of retinol and IgE between groups. Conclusions　These results suggest that β-carotene could improve nasal symptoms of PAR and QOL in subjects without SAR symptoms. These effects would be due to β-carotene, not vitamin A, a metabolic product of β-carotene. （UMIN：UMIN000037921

Objective　This study aimed to assess benefit of a Lactobacillus paracasei subsp. paracasei NY1301-containing beverage on intestinal health. Methods　A randomized, placebo-controlled, double blind, parallel-group study was conducted in constipated subjects who consumed placebo（n＝49）or active food（containing 1×1011 cells of NY1301 daily）（n＝50）for 2 weeks after a 1-week pre-observation period. The changes in parameters of defecation and intestinal flora population were assessed. Results　Active food group had significantly higher lactobacillus occupancy among stool eubacteria than placebo group. The difference was found in all of the subject subpopulations stratified on basis of age and stool frequency. In addition, defecation frequency was significantly higher in younger subjects（aged 24-36）in active food group than the corresponding population in placebo group. There were no adverse events related to the investigational food intake. Conclusion　The intake of the L. paracasei subsp. paracasei NY1301 can benefit intestinal environment. （UMIN ID: UMIN000035202）

A placebo-controlled, randomized, parallel-group, double-blind human clinical study was performed in 90 healthy mid- to senior age adults. Participants were orally administered a placebo or a composite dietary supplement containing propolis extract, Gingko biloba extract, phosphatidylserine and curcumin（active）for 12 weeks. Cognitive function evaluated by MCI screening and Cognitrax, and various blood or urine markers were measured at pre- and post-administration. Data from 82 subjects（placebo 40, active 42）who completed the study and were eligible were analyzed. Compared to the placebo group, the active group showed significant improvement in Stroop（ST）commission errors which indicate attention, concentration, and judging ability in Cognitrax; MPI score which is an indicator of verbal memory and attention in MCI screen; and three immediate recall task score in MCI screen. Blood levels of TNF-α and AST were lowered, and subjective symptoms of sleep quality and Social Functioning in SF-36 were significantly improved compared to placebo. Furthermore, Cognitrax scores from 20 subjects whose BDNF were less than the first quartile were analyzed. Compared to the placebo group, the active group showed a significant improvement in neurocognitive index which is the total score, as well as indications for attention, concentration, and judgment, namely“, cognitive flexibility, executive function and Shifting attention（SAT）correct response”. No severe adverse events were observed in any of the groups. This study demonstrates that the intake of composite dietary supplement safely improves cognitive functions, such as verbal memory, attention, concentration, and judgement, sleep quality and liver function through anti-inflammation. （UMIN 000038465）