New Drug Research Center Inc

Hokkaido, Japan

New Drug Research Center Inc

Hokkaido, Japan

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Ukawa Y.,Central Research Institute ITO EN Ltd. | Sagesaka Y.,Central Research Institute ITO EN Ltd. | Hatakeyama Y.,New Drug Research Center Inc. | Noro A.,New Drug Research Center Inc. | Fukuhara I.,Fukuhara Clinic
Japanese Pharmacology and Therapeutics | Year: 2013

Objective: We examined the effect of catechins with a galloyl moiety to reduce dietary lipid absorption in humans. Methods: A randomized double-blind placebo-controlled crossover study was conducted. The beverage (340 mL/bottle) contained 190.9 mg of tea catechins with a galloyl moiety. Fifteen healthy adult subjects were randomly divided into two groups. Group A was requested to consume the drinks, containing catechins with a galloyl moiety, everyday for 10 days and then the placebo for 10 days, after an 11 day interval between these intake periods. On the contrary, Group B consumed the placebo first for 10 days and then the catechin drinks for 10 days, after an 11 day interval between the periods. Each subject in the catechin group was given 3 bottles of the test beverage/day and each subject in the placebo group was given 3 bottles of the placebo beverage/day. During the treatment period, subjects were given the same menu (Male : 2244±35.6 kcal, 84±0.6 g lipids, Female : 1944±35.6 kcal, 66±0.6 g lipids) at each meal. On the last 3 days of each treatment period, feces were collected in order to measure the excretion of lipids. Results: Lipid excretion into feces was found to be significantly higher in the test beverage consumption cases than in the placebo beverage ones on third day. Serum total cholesterol and LDL cholesterol were significantly lower in the test beverage consumption cases than in the placebo beverage ones. Conclusions: Our present observations suggest that consumption of catechins with a galloyl moiety could increase lipid excretion into feces.


Badmaev V.,New Hill | Hatakeyama Y.,New Drug Research Center Inc. | Yamazaki N.,New Drug Research Center Inc. | Noro A.,New Drug Research Center Inc. | And 5 more authors.
Journal of Functional Foods | Year: 2015

The herbal compositions of Coleus forskohlii, Salacia reticulata, and Sesamum indicum, standardized for forskolin, mangiferin, and sesamin, respectively, were shown, in vitro, to inhibit pancreatic lipase with differing degrees and dynamics. In the placebo controlled six weeks clinical study the daily intake of 1000 mg C. forskohlii stand-alone standardized for 10% forskolin, showed statistically significant lowering of total body fat vs. baseline and placebo group (p < 0.05). The computerized tomography showed decrease of total body fat and visceral fat in C. forskohlii group in comparison to the baseline. The potential of three herbal extracts preventing dietary fat absorption was emphasized by the in vitro synergy between C. forskohlii and S. reticulata inhibiting pancreatic lipase at higher rate than the fat-blocking activity generated by each component alone. The in vitro addition of S. indicum to the formula was found to synergistically assist inhibition of the pancreatic lipase in a lower dose range, while moderating the pancreatic lipase inhibition in a higher dose range. This dual mechanism of S. indicum was postulated as a safety mechanism preventing any potential side effects resulting from excessive inhibition of pancreatic lipase activity. © 2015 Elsevier Ltd.


Takahashi-Niki K.,Hokkaido University | Inafune A.,New Drug Research Center Inc. | Michitani N.,New Drug Research Center Inc. | Hatakeyama Y.,New Drug Research Center Inc. | And 6 more authors.
Journal of Pharmacological Sciences | Year: 2015

Parkinson's disease (PD) is caused by dopaminergic cell death in the substantia nigra, leading to a reduced level of dopamine in the striatum. Oxidative stress is one of the causes of PD. Since symptomatic PD therapies are used, identification of compounds or proteins that inhibit oxidative stress-induced neuronal cell death is necessary. DJ-1 is a causative gene product of familial PD and plays a role in anti-oxidative stress reaction. We have identified various DJ-1-binding compounds, including compound-23, that restored neuronal cell death and locomotion defects observed in neurotoxin-induced PD models. In this study, wild-type and DJ-1-knockout mice were injected intraperitoneally with 1 mg/kg of compound-23 and then with 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at 1 h after injection. Five days after administration, the effects of compound-23 on MPTP-induced locomotion deficits, on dopaminergic cell death and on brain dopamine levels were analyzed by rotor rod tests, by staining cells with an anti-TH antibody and by an HPLC, respectively. The results showed that compound-23 inhibited MPTP-induced reduction of retention time on the rotor rod bar, neuronal cell death in the substantia nigra and striatum and dopamine content in wild-type mice but not in DJ-1-knockout mice, indicating a DJ-1-dependent effect of compound-23.


Nakao K.,NUTRI Co. | Hara K.,NUTRI Co. | Kusubata M.,Nippi Inc. | Igarashi M.,New Drug Research Center Inc. | And 2 more authors.
Japanese Pharmacology and Therapeutics | Year: 2013

Objective: Effects of collagen peptide ingestion on healing of skin wound were examined in a rat model of pressure ulcer in comparison with effects of arginine known as a good ingredient. Methods: SD rats aged 8 weeks were fed a low protein diet (AIN-93M; 10% protein), and pressure ulcers were experimentally induced at 9 weeks of age. 0.2 g/kg/day collagen peptide, or 0.1 or 0.2 g/kg/day arginine was administered twice a day, half of a total daily dose each time. Healing process was compared among the control group and the experimental groups with regard to the daily wound area ratio, sum of daily wound area ratio, time and ratio of healing of pressure ulcer, and biochemical markers of blood. Results: Wound area ratio was significantly smaller in the collagen peptide group and the arginine groups compared with the control group. Sum of daily wound area ratio was significantly smaller in the collagen peptide group but not in the arginine groups. Time and ratio of healing was significantly smaller in the collagen peptide group and the 0.2 g/kg/day arginine group. Collagen peptide-derived hydroxyprolylglycine that promotes wound healing of the skin in blood was significantly higher in the collagen peptide group. Conclusions: The ingestion of collagen peptide promotes healing of pressure ulcers with effectiveness similar to the ingestion of arginine. The action mechanism of collagen peptide may differ from that of arginine.


PubMed | Kyoto Pharmaceutical University, New Drug Research Center Inc. and Hokkaido University
Type: Journal Article | Journal: Journal of pharmacological sciences | Year: 2015

Parkinsons disease (PD) is caused by dopaminergic cell death in the substantia nigra, leading to a reduced level of dopamine in the striatum. Oxidative stress is one of the causes of PD. Since symptomatic PD therapies are used, identification of compounds or proteins that inhibit oxidative stress-induced neuronal cell death is necessary. DJ-1 is a causative gene product of familial PD and plays a role in anti-oxidative stress reaction. We have identified various DJ-1-binding compounds, including compound-23, that restored neuronal cell death and locomotion defects observed in neurotoxin-induced PD models. In this study, wild-type and DJ-1-knockout mice were injected intraperitoneally with 1mg/kg of compound-23 and then with 30mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at 1h after injection. Five days after administration, the effects of compound-23 on MPTP-induced locomotion deficits, on dopaminergic cell death and on brain dopamine levels were analyzed by rotor rod tests, by staining cells with an anti-TH antibody and by an HPLC, respectively. The results showed that compound-23 inhibited MPTP-induced reduction of retention time on the rotor rod bar, neuronal cell death in the substantia nigra and striatum and dopamine content in wild-type mice but not in DJ-1-knockout mice, indicating a DJ-1-dependent effect of compound-23.


Nagatomo A.,Morishita Jintan Co | Nishida N.,Morishita Jintan Co | Fukuhara I.,Fukuhara Clinic | Noro A.,New Drug Research Center Inc | And 3 more authors.
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy | Year: 2015

Background: Obesity has become a great problem all over the world. We repeatedly screened to find an effective food to treat obesity and discovered that rosehip extract shows potent antiobesity effects. Investigations in mice have demonstrated that rosehip extract inhibits body weight gain and decreases visceral fat. Thus, the present study examined the effect of rosehip extract on human body fat in preobese subjects. Methods: We conducted a 12-week, single-center, double-blind, randomized, placebo-controlled study of 32 subjects who had a body mass index of ≥25 but <30. The subjects were assigned to two random groups, and they received one tablet of placebo or rosehip that contained 100 mg of rosehip extract once each day for 12 weeks with no dietary intervention. Abdominal fat area and body fat percent were measured as primary outcomes. The other outcomes were body weight and body mass index. Results: Abdominal total fat area, abdominal visceral fat area, body weight, and body mass index decreased significantly in the rosehip group at week 12 compared with their baseline levels (P<0.01) after receiving the rosehip tablet intake, and the decreases in these parameters were significantly higher when compared with those in the placebo group. Additionally, body fat percent tended to decrease compared with the placebo group and their baseline level. Moreover, the abdominal subcutaneous fat area was significantly lower in the rosehip group than in the placebo group at week 12 after the initiation of intake (P<0.05). In addition, there were no abnormalities, subjective symptoms, and findings that may indicate clinical problems during the study period. Conclusion: These results suggest that rosehip extract may be a good candidate food material for preventing obesity. © 2015 Nagatomo et al.


PubMed | Morishita Jintan Co, Fukuhara Clinic and New Drug Research Center Inc.
Type: | Journal: Diabetes, metabolic syndrome and obesity : targets and therapy | Year: 2015

Obesity has become a great problem all over the world. We repeatedly screened to find an effective food to treat obesity and discovered that rosehip extract shows potent anti-obesity effects. Investigations in mice have demonstrated that rosehip extract inhibits body weight gain and decreases visceral fat. Thus, the present study examined the effect of rosehip extract on human body fat in preobese subjects.We conducted a 12-week, single-center, double-blind, randomized, placebo-controlled study of 32 subjects who had a body mass index of 25 but <30. The subjects were assigned to two random groups, and they received one tablet of placebo or rosehip that contained 100 mg of rosehip extract once each day for 12 weeks with no dietary intervention. Abdominal fat area and body fat percent were measured as primary outcomes. The other outcomes were body weight and body mass index.Abdominal total fat area, abdominal visceral fat area, body weight, and body mass index decreased significantly in the rosehip group at week 12 compared with their baseline levels (P<0.01) after receiving the rosehip tablet intake, and the decreases in these parameters were significantly higher when compared with those in the placebo group. Additionally, body fat percent tended to decrease compared with the placebo group and their baseline level. Moreover, the abdominal subcutaneous fat area was significantly lower in the rosehip group than in the placebo group at week 12 after the initiation of intake (P<0.05). In addition, there were no abnormalities, subjective symptoms, and findings that may indicate clinical problems during the study period.These results suggest that rosehip extract may be a good candidate food material for preventing obesity.


Nishimura D.,Nissei Bio Company | Nishimura D.,Gene Trophology Institute | Takahashi C.,Nissei Bio Company | Takahashi C.,Gene Trophology Institute | Kohzai Y.,New Drug Research Center Inc.
Nippon Shokuhin Kagaku Kogaku Kaishi | Year: 2015

Society as a whole is developing a more nocturnal lifestyle as a result of advances in information technology and the increasing number of nighttime jobs. These changes in lifestyle have ledto delayedbed time andd eclining hours of sleep. A relationship between sleep disturbance and the deterioration in physical and mental health has recently been reported; specifically, the negative effects of sleep disturbance on brain and/or immune functions as well as lifestyle disease pathogenesis. Furthermore, the number of individuals with sleep disorders has been increasing with aging, representing a problem that needs to be addressed. We conducted a double-blind crossover study in 10 male subjects (age range, 40-69 years) who reported dissatisfaction with their sleep. Our aim was to determine the effect of asparagus cladophylls intake on sleep disturbance. The Pittsburgh Sleep Quality Index questionnaire revealed a significant reduction in sleep disturbance in response to cladophylls intake. Thus, asparagus cladophylls intake was foundto improve sleep. Copyright © 2015, Japanese Society for Food Science and Technology.


Nakano M.,Chiyoda Corporation | Takahashi H.,New Drug Research Center Inc. | Koura S.,New Drug Research Center Inc. | Chung C.,Intertek | And 2 more authors.
Regulatory Toxicology and Pharmacology | Year: 2014

The potential use of pyrroloquinoline quinone disodium salt (BioPQQ™), as a supplemental food ingredient, was evaluated in a range of oral toxicity studies in rats including an acute study, a 14-day preliminary and a 28-day repeated-dose study, and a 13-week subchronic study. The median lethal dose of BioPQQ™ was shown to be 1000-2000. mg/kg body weight (bw) in male and 500-1000. mg/kg. bw in female rats. In the 14-day study, high doses of BioPQQ™ resulted in increases in relative kidney weights with associated histopathology in female rats only, while a follow-up 28-day study in female animals resulted in increases in urinary protein and crystals. These findings were reversible, and resolved during the recovery period. In the 13-week study, a number of clinical chemistry findings and histopathological changes were noted, which were deemed to be of no toxicological significance, as the levels were within the historical control range, were not dose-dependent, occurred at a similar frequency in control groups, or only occurred in the control group. Based on these findings, a no-observed-adverse-effect level of 100. mg/kg. bw/day was determined for BioPQQ™ in rats, the highest dose tested in the 13-week study. © 2014 .


PubMed | Chiyoda Corporation, New Drug Research Center Inc. and Intertek
Type: Journal Article | Journal: Regulatory toxicology and pharmacology : RTP | Year: 2014

The potential use of pyrroloquinoline quinone disodium salt (BioPQQ), as a supplemental food ingredient, was evaluated in a range of oral toxicity studies in rats including an acute study, a 14-day preliminary and a 28-day repeated-dose study, and a 13-week subchronic study. The median lethal dose of BioPQQ was shown to be 1000-2000mg/kg body weight (bw) in male and 500-1000mg/kgbw in female rats. In the 14-day study, high doses of BioPQQ resulted in increases in relative kidney weights with associated histopathology in female rats only, while a follow-up 28-day study in female animals resulted in increases in urinary protein and crystals. These findings were reversible, and resolved during the recovery period. In the 13-week study, a number of clinical chemistry findings and histopathological changes were noted, which were deemed to be of no toxicological significance, as the levels were within the historical control range, were not dose-dependent, occurred at a similar frequency in control groups, or only occurred in the control group. Based on these findings, a no-observed-adverse-effect level of 100mg/kgbw/day was determined for BioPQQ in rats, the highest dose tested in the 13-week study.

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