Areas covered: The current review covers patent literature published between January 2012 and May 2018. Queries were performed on Espacenet, SciFinder, clinicaltrials.gov, pharmacodia.com, and the websites of pharmaceutical companies.
Expert opinion: Several novel therapeutic applications have been proposed for 5-HT1AR ligands, i.e. prostate cancer treatment, gastrointestinal and cardiopulmonary disorders, facilitation of urination and defecation, and L-DOPA-induced dyskinesia. Interestingly, no patent application has been filed by big pharma companies, while numerous researches are being conducted in smaller companies and academia. 相似文献
Research design and methods: Multicenter survey, open-label study of 49 Japanese COPD patients aged ≥ 40 years; outpatients with >10 pack years of smoking history; ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 70%; predicted FEV1 < 80%; treated with bronchodilators and/or inhaled corticosteroids as maintenance therapy until week 48.
Main outcome measures: The primary endpoint was change in pulmonary function (trough FEV1, trough FVC); secondary endpoints were QOL and physical activity at 48 weeks after initiation of therapy.
Results: Airway reversibility was confirmed in untreated patients. Significant changes over time were not observed for FEV1 and FVC, indicating lung function at initiation of treatment was maintained during the observation period. COPD assessment test scores showed statistical and clinical improvements. Cough, sputum, breathlessness, and shortness of breath were significantly improved.
Conclusions: Lung function and QOL of untreated Japanese COPD patients improved and improvements were maintained by performing a therapeutic intervention that conformed to published guidelines. 相似文献
Objective: Identification of compounds from C. rotundus rhizomes responsible for the inhibition of α-glucosidase and α-amylase.
Materials and methods: Compounds were identified by a phytochemical investigation using combined chromatographic and spectroscopic methods. α-glucosidase and α-amylase inhibitory activities were evaluated by in vitro enzyme inhibition assays.
Results: A new (2RS,3SR)-3,4′,5,6,7,8-hexahydroxyflavane (1), together with three known stilbene dimers cassigarol E (2), scirpusin A (3) and B (4) were isolated. Compound 2 inhibited both α-glucosidase and α-amylase activities while the flavane 1 only showed effect on α-amylase, and compounds 3 and 4 were active on α-glucosidase. All four compounds showed significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity.
Discussion: The inhibitory activities against α-amylase and α-glucosidase of the C. rotundus rhizomes were reported for the first time. Stilbene dimers are considered as potent inhibitors of α-glucosidase and promising antihyperglycemic agents.
Conclusion: The isolated compounds may contribute to the antidiabetic property of C. rotundus. 相似文献
Methods: Healthy male subjects (N = 91) were randomized 1:1:1 to receive a single intravenous infusion of 1 mg/kg of BI 695502 or US- or EU-approved Avastin. An interim analysis was planned when ~50% of subjects were evaluable for the primary end point to determine if the prespecified criteria for bioequivalence were achieved; if demonstrated, the study could be stopped early. The primary end point was area under the concentration–time curve (AUC) of the analyte in plasma from time zero extrapolated to infinity (AUC0–∞). Other pharmacokinetic (PK) parameters, safety, and in vitro binding affinity were also evaluated.
Results: The interim analysis demonstrated three-way bioequivalence for all comparisons. The confidence intervals around the geometric mean ratios of the primary and secondary PK parameters were within the predefined acceptance ranges. Study drugs were well tolerated with no clinically relevant differences in safety.
Conclusion: BI 695502 and US- and EU-approved Avastin showed three-way bioequivalence with similar safety profile.
Clinical trial registration: NCT01608087. 相似文献
Methods: N-glucuronidation potential of four piperazine-containing drugs, namely two antihistamines (i.e. cyclizine and chlorcyclizine) and two tetracyclic antidepressants (i.e. mirtazapine and mianserin), was determined by using expressed UDP-glucuronosyltransferase (UGT) enzymes and liver microsomes from both human and animals.
Results: Among 13 expressed UGT enzymes, only UGT1A4 and UGT2B10 showed conjugating activities toward these four drugs. Reaction phenotyping, chemical inhibition, and activity correlation analysis revealed that UGT2B10 was a high-affinity enzyme and mainly responsible for hepatic N-glucuronidation of all drugs except mianserin. Both UGT1A4 and UGT2B10 were important contributors to mianserin N-glucuronidation. Moreover, significant species differences were observed in N-glucuronidation of all test drugs. In particular, liver microsomes from four experimental animals (i.e. mouse, rat, dog, and monkey) showed none or negligible activity in catalyzing N-glucuronidation of four drugs.
Conclusions: UGT2B10 plays a critical role in N-glucuronidation of piperazine-containing drugs. Also, conventional experimental animals might be inappropriate models for studying human N-glucuronidation.
Abbreviations: CLint: intrinsic clearance; CLmax: maximal clearance; HLM: human liver microsomes; Km: Michaelis–Menten constant; Ki: substrate inhibition constant; MS: mass spectroscopy; NNAL: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol; QTOF: Quadrupole time-of-flight; S50: the substrate concentration resulting in 50% of Vmax; UDP-GlcA: uridine diphosphoglucuronic acid; UGT: UDP-glucuronosyltransferase; UPLC: ultra performance liquid chromatography; Vmax: maximal velocity. 相似文献
Objective: This review analyzes and summarizes the ethnopharmacological applications, phytochemistry, and pharmacological activities and molecular mechanisms of L. coreana.
Methods: Related literature (from 1998 to 2016) was obtained and compiled via searching databases including Scopus, Web of Science, Google Scholar, CNKI and PubMed. Keywords (Litsea coreana, hawk tea, eagle tea and laoying cha) were used to select the articles.
Results: Studies indicate that L. coreana contains characteristic polysaccharides, polyphenols, essential oils, and numerious flavonoids, which exhibit remarkable bioactivities, such as hepatoprotection, hyperglycaemia, anti-inflammation, antioxidation and antibacterial, through multiple molecular mechanisms.
Conclusion: This paper provides a systematic review on the phytochemicals and pharmacological activities of L. coreana which should be useful for further study and application of this medicinal herb. 相似文献
Objective: This study aimed to determine the protective effects of the osmolyte taurine against blue light-induced apoptosis in retinal neuronal cells in vitro.
Methods: Real-time PCR was used to measure osmolyte transport. Radioimmunoassays were performed to measure osmolyte uptake. Cell Counting Kit-8 assays were conducted to measure cellular viability. Flow cytometry analysis was used to measure apoptosis.
Results: Compared with normotonic stress, hypertonic stress-induced uptake of osmolytes, including betaine, myoinositol, and taurine, into the retinal neuronal cells. Blue light increased osmolyte transporter mRNA expression together with osmolyte uptake. Furthermore, taurine significantly suppressed blue light-induced retinal neuronal cell apoptosis.
Conclusion: The compatible osmolyte taurine may have an important role in cell resistance to blue light and cell survival. 相似文献
Methods: This post-hoc pooled analysis used data from two Phase III clinical studies involving 702 Japanese patients. We evaluated teneligliptin as monotherapy and combined with a sulfonylurea, glinide, biguanide, or α-glucosidase inhibitor. Safety measures included adverse events (AEs), adverse reactions and hypoglycemia. The main efficacy measure was the change in glycated hemoglobin (HbA1c) from baseline.
Results: Incidences of AEs and adverse reactions were similar among the teneligliptin monotherapy group and all combination therapy groups except the combination with sulfonylurea. Hypoglycemia was more frequent in the sulfonylurea combination therapy group than in other groups. Teneligliptin administered once daily as monotherapy or combination therapy resulted in a decrease in HbA1c, which was maintained for 52 weeks. Bodyweight showed no change or a slight increase at the end of 52 weeks in all groups.
Conclusions: This pooled analysis provides evidence for the safety and efficacy of long-term use of teneligliptin as monotherapy or combination therapy in Japanese T2DM patients. 相似文献
Objective: This review aims to synthesize recent developments in Echinacea biotechnology and to identify promising applications for these advances in the industry.
Methods: A comprehensive survey of peer-reviewed publications was carried out, focusing on Echinacea biotechnology and impacts on phytochemistry. This article primarily covers research findings since 2007 and builds on earlier reviews on the biotechnology of Echinacea.
Results: Bioreactors, genetic engineering and controlled biotic or abiotic elicitation have the potential to significantly improve the yield, consistency and overall quality of Echinacea products. Using these technologies, a variety of new applications for Echinacea can be realized, such as the use of seed oil and antimicrobial and immune boosting feed additives for livestock.
Conclusions: New applications can take advantage of the well-established popularity of Echinacea as a NHP. Echinacea presents a myriad of potential health benefits, including anti-inflammatory, anxiolytic and antibiotic activities that have yet to be fully translated into new applications. The distinct chemistry and bioactivity of different Echinacea species and organs, moreover, can lead to interesting and diverse commercial opportunities. 相似文献
Objective: To isolate and identify bioactive constituents from the whole herb of V. axillare.
Materials and methods: Ethanol extract of the whole herb of V. axillare was subjected to successive column chromatography. Chemical structures of the compounds were elucidated by detailed spectroscopic analyses on the basis of NMR, IR and HR-MS data.
Results: A new monoterpenoid, axillacetal A (1) and a known analogue, tarumal (2), were isolated from the whole herb of V. axillare. The structure of tarumal (2) was also revised according to our NMR data.
Discussion and conclusion: This is the first report on the isolation and authentication of novel chemical constituents from V. axillare. 相似文献
Areas covered: This review summarizes the available data for orally administered antimicrobials routinely used as monotherapy for MRSA infections. We make recommendations and highlight the current gaps in the literature. A PubMed (1966 – Present) search was performed to identify relevant literature for this review.
Expert commentary: There is a vast divide in the amount of pharmacokinetic/pharmacodynamic data to guide dosing decisions for older MRSA agents compared with the oxazolidenones.
Five-year view: Additional retrospective data will become available for the older MRSA agents in severe MRSA infections. 相似文献
Research design and methods: The single-center, open-label, randomized, three-period, three-sequence, reference-replicated, cross-over study included 38 healthy subjects under fed conditions. In each study period (separated by a 14-day washout), a single oral dose of the test (T) or reference (R) product was administered. Blood samples were collected at pre-dose and up to 72.0 h after administration. The calculated pharmacokinetic parameters, based on the plasma concentrations of itraconazole and hydroxy itraconazole, were AUC0-72h, AUC0-∝, Cmax, Tmax, T1/2 and Kel.
Results: The 90% CI for the test/reference geometric means ratio for the parent compound, itraconazole, was in the range from 85.29% to 116.07% for AUC0-72h. Since the coefficient of variation (CV) for the reference product was 44.95% for Cmax, the 90% CI for this parameter for itraconazole was 93.49–133.78%, which was within the proposed limits of the EMA for bioequivalence of 72.15–138.59%. During the study, 4 subjects encountered a total of 14 mild adverse events.
Conclusions: The use of the reference-scaling approach with 3-period design (TRR, RTR, and RRT) was an efficient way to demonstrate that two commercially available oral itraconazole formulations met the predetermined bioequivalence criteria. 相似文献
Methods: In a randomized clinical trial 44 patients with acute bacterial meningitis were randomly assigned to the conventional- or high-dose vancomycin groups. Clinical and laboratory parameters were used for evaluation of response to the treatment regimens.
Results: In the high-dose group, leukocytosis and fever resolved significantly faster than those in the conventional group. Furthermore, the length of hospitalization was shorter and Glasgow Coma Scale at the end of 10th day was significantly lower in the high dose compared to the conventional group. Trend of creatinine clearance changes did not differ significantly between the two groups.
Conclusion: In comparison to the conventional-dose regimen, the high-dose vancomycin regimen was associated with significantly more favorable clinical response without increase in the incidence of nephrotoxicity in patients with acute bacterial meningitis. 相似文献
Objective: We investigated the effect of UV light on the histamine content of pollen and examined if an irradiation of pollen affects the viability and proliferation of conjunctival cells.
Materials and methods: Alder (Alnus glutinosa) and hazel (Corylus avellana) pollen were irradiated for different time periods with sunlight, UV-A or UV-B light and the histamine content was analysed and compared with non-irradiated pollen. Conjunctival epithelial cells (CHANG cells) were exposed to irradiated and non-irradiated pollen followed by an assessment of cell viability with the colorimetric MTS test and the impedance-based measurement of cell proliferation using the xCELLigence real-time analysis system.
Results: UV light irradiation increased the histamine level of alder and hazel pollen in a dose-dependent manner. CHANG cells treated with irradiated pollen induced a statistically significant higher decrease of cell viability than treatment with non-irradiated pollen.
Discussion and conclusions: Our results indicate that UV light is able to alter pollen thus making them more harmful for conjunctival cells. 相似文献
Areas covered: This article reviews the pathophysiology as well as pharmacological aspects of PONV prophylaxis and treatment. Relevant strategic aspects for pharmacological prophylaxis of PONV are discussed and clinical standard operating procedures are presented.
Expert opinion: The expert opinion focuses on poor implementation of actual PONV guidelines and future considerations. 相似文献
Objective: The present review compiles and summarizes the chemical compositions, biological properties and clinical efficacy of mulberry leaves that are related to the amelioration of cardiometabolic risks.
Methods: Published English literature from the PubMed, Science Direct and Google Scholar databases was searched by using ‘mulberry leaves’ ‘Morus spp.’, ‘hyperglycemia’, ‘hyperlipidemia’, ‘obesity’, ‘hypertension’, ‘oxidative stress’, ‘atherosclerosis’ and ‘cardiovascular diseases’ as the keywords. The relevant articles published over the past two decades were identified and reviewed.
Results: Mulberry leaves contain numerous chemical constituents. 1-Deoxynojirimycin (DNJ), phenolics and flavonoids are the prominent functional compounds. Preclinical and clinical studies showed that mulberry leaves possessed various beneficial effects against cardiometabolic risks, including antihyperglycaemic, antihyperlipidaemic, antiobesity, antihypertensive, antioxidative, anti-inflammatory, anti-atherosclerotic and cardioprotective effects.
Conclusions: Mulberry leaves could be a promising therapeutic option for modulating cardiometabolic risks. However, further investigations should be performed to substantiate the potential of mulberry leaves in practical uses. 相似文献
Methods: Safety was assessed in two controlled and two open-label studies in blind individuals with Non-24 and in two controlled studies of primary insomnia. Periodic assessments included collection of adverse events (AEs), laboratory testing, electrocardiograms (ECGs), vital sign monitoring, physical examinations and assessment for the potential for suicide. One study included additional assessments for endocrine function.
Results: A total of 184 blind individuals with Non-24 received tasimelteon nightly with a median exposure > 1 year. In placebo-controlled studies, 387 patients with insomnia and 42 patients with Non-24 received tasimelteon nightly for 4 – 26 weeks. The total patient years exposure for the six studies assessed here is 258.64 patient years. Discontinuations due to AEs were similar across treatment groups. Overall in the clinical studies described here, AEs attributable to tasimelteon treatment were headache, diarrhea, dry mouth, alanine aminotransferase increased, somnolence, dizziness and nightmare/abnormal dreams. There were no clinically significant differences in treatment group with ECGs, vital signs, withdrawal, endocrine function and suicidality assessments.
Conclusion: Long-term tasimelteon administration was safe and well-tolerated. This is supported by placebo-controlled data in both Non-24 and insomnia patients. 相似文献
Objective: To describe the first case of a patient with a spontaneous corneal perforation associated with mucocutaneous ulcerations while taking Nicorandil.
Materials and methods: A 81-year-old patient, with no past history of ocular disease but a long past history of cardiovascular disease, presented with a spontaneous paracentral corneal perforation. This was consecutive to 5 months of recurrent keratoconjunctivitis and mucocutaneous ulcerations resistant to conventional therapy. (He was taking nicorandil for 5 years.) A penetrating keratoplasty was performed in emergency.
Results: Inflammatory and infectious causes of spontaneous corneal perforation were ruled out. After initial uneventful post-operative wound healing, an epithelial ulcer appeared on the graft. Dermatologists suggested the iatrogenic role of nicorandil and the drug was discontinued. Both mucocutaneous and corneal ulcerations resolved rapidly.
Discussion: Although mucocutaneous ulcerations have been attributed several times to nicorandil, this is, to our knowledge, the first major corneal damage due to this antianginal drug. Timing, pattern of illness, absence of other aetiology, recurrence of epithelial ulceration on the corneal graft and its spontaneous healing after nicorandil discontinuation make it highly apparent probable that nicorandil was directly involved in this corneal perforation.
Conclusion: Ophthalmologists and dermatologists should be aware of the risk of severe but reversible corneal ulcerations in patients treated with nicorandil. A pharmacovigilance warning statement should be compulsory. 相似文献
Objective: A double-blind, placebo-controlled, comparative study of 473 pediatric PAR patients (7 – 15 years old) to determine the superiority and safety of bepotastine besilate (10 mg twice daily) relative to placebo for improved total and individual nasal symptom scores compared with baseline.
Research design and methods: Subjects were randomized to placebo (n = 233) or bepotastine besilate (n = 240, 10 mg orally twice daily for 2 weeks). Interference of daily life by PAR was assessed by measuring change in individual nasal symptom scores from baseline.
Results: Bepotastine besilate was superior to placebo in terms of total nasal symptom scores, with improved overall nasal symptoms of PAR compared with baseline values. Subgroup analyses demonstrated bepotastine besilate was effective irrespective of age, sex or body weight. No clinically significant adverse drug reactions often observed with first-generation antihistamines were reported and no difference in adverse events between groups was observed.
Conclusions: Bepotastine besilate is effective and safe for pediatric PAR patients aged 7 – 15 years, and has a significant clinical impact on PAR. Clinical trial registration: ClinicalTrials.gov identifier: NCT01861522 (https://clinicaltrials.gov/ct2/show/NCT01861522). 相似文献