Multiple Active Ingredients Research Articles

Preparation of multilayered polymeric structures using a novel four-needle coaxial electrohydrodynamic device.

Coaxial four-needle electrohydrodynamic forming is applied for the first time to prepare layered structures in both particle and fiber form. Four different biocompatible polymers, polyethylene glycol, poly (lactic-co-glycolic acid), polycaprolactone, and polymethylsilsesquioxane, are used to generate four distinct layers confirmed using transmission and scanning electron microscopy combined with focused ion beam milling. The incorporation and release of different dyes within the polymeric system of four layers are demonstrated, something that is much desired in modern applications such as the polypill where multiple active pharmaceutical ingredients can be combined to treat numerous diseases.

Impact of Chinese Herbal Medicine on American Society and Health Care System: Perspective and Concern

Many Americans, not completely satisfied with traditional western medicine, have turned to alternative and complementary medicine which explains the increasing popularity of the herbal products and the Chinese herbal medicine. The lack of government regulations and the increasing advertisements by the manufactures have created an impression to the common public that the natural herbal remedies are inherently safer and cheaper than conventional medicine. The skyrocketing rise of healthcare cost and the adverse reaction and side effects incurred from the prescribed drugs have both reinforced such an impression. Herbs in the USA and in many European countries have been prepared as capsules, tablets, teas, lozenges, juice extracts, tincture, and ointments. Most of the herbs are administered as a single herb in the USA and Europe. However, the traditional Chinese herbal medicine contains multiple active ingredients from various herbs and is prepared as concoctions by simmering them for hours to produce pharma-therapeutic properties useful for the treatment of a particular disease. Those prepared concoctions are taken gingerly with specific treatment purposes. In the USA and some European counties, herbs are distributed and labeled as dietary supplements and are taken by many individuals for a long period of time creating some medical and dental complex problems among them, especially in terms of anesthesia-surgery complications. This paper provides insight into basic differences in how herbs are prepared before administration to the patients in China versus a single unprepared herb sold in the USA and Europe. Also addressed are the interdisciplinary issues with health professionals, the proper regulations for better quality control of imported herbs, and the proper warning on the labels of the herbs.

Efficacy and safety of medicinal plants used in the management of diabetes mellitus.

Efficacy and safety of medicinal plants used in the management of diabetes mellitus.

Fungicide Efficacy Against Calonectria pseudonaviculata, Causal Agent of Boxwood Blight.

Calonectria pseudonaviculata causes leaf spot and stem lesions resulting in defoliation and dieback of boxwood. Fungicides representing 20 different active ingredients from 13 different Fungicide Resistance Action Committee groups were evaluated for their effects on conidial germination and mycelial growth using in vitro assays, and the concentration that suppressed fungal growth to 15% of that on unamended media (EC85) values were determined. A number of fungicides strongly inhibited mycelial growth of C. pseudonaviculata. Four demethylation inhibitor fungicides had EC85 values of 1.2 μg a.i./ml or less. Thiophanate-methyl, fludioxonil, pyraclostrobin, trifloxystrobin, kresoxim-methyl, mancozeb, and chlorothalonil also had activity against mycelial growth. Fludioxonil + cyprodinil had a lower EC85 than the same rate of fludioxonil alone, suggesting that cyprodinil had activity against mycelial growth. Fungicides that inhibited C. pseudonaviculata conidial germination include pyraclostrobin, trifloxystrobin, and kresoxim-methyl as well as fludioxonil, mancozeb, chlorothalonil, and boscalid. Quinoxyfen, etridiazole, fenhexamid, hymexazol, famoxadone, and cymoxanil did not inhibit either C. pseudonaviculata conidial germination or mycelial growth. In comparison with values found in the literature, EC50 values for kresoxim-methyl were up to 10 times higher than reported previously, suggesting that fungicide insensitivity may have developed. Protectant fungicides with activity against conidial germination and systemic fungicides with activity against mycelial growth, such as those identified here, may be complementary to achieve the high levels of pathogen management required for control of this disease. In addition, multiple fungicide active ingredients from different mode-of-action groups used in mixtures or over time may also act to slow selection for fungicide insensitivity.

Design of multiligand inhibitors for the swine flu H1N1 neuraminidase binding site

Viral neuraminidase inhibitors such as oseltamivir and zanamivir prevent early virus multiplication by blocking sialic acid cleavage on host cells. These drugs are effective for the treatment of a variety of influenza subtypes, including swine flu (H1N1). The binding site for these drugs is well established and they were designed based on computational docking studies. We show here that some common natural products have moderate inhibitory activity for H1N1 neuraminidase under docking studies. Significantly, docking studies using AutoDock for biligand and triligand forms of these compounds (camphor, menthol, and methyl salicylate linked via methylene bridges) indicate that they may bind in combination with high affinity to the H1N1 neuraminidase active site. These results also indicate that chemically linked biligands and triligands of these natural products could provide a new class of drug leads for the prevention and treatment of influenza. This study also highlights the need for a multiligand docking algorithm to understand better the mode of action of natural products, wherein multiple active ingredients are present.

OTC combination products in pharmacistassisted self-care

Over-the-counter (OTC) medicines provide a convenient, costeffective means to treat self-identifi ed symptoms and help to lessen the burden on the health care system by reducing the number of doctor visits and associated prescription costs. Containing either a single active ingredient or a combination of multiple active ingredients, OTC medicines are used by consumers for a number of reasons, including familiarity with self-treatment, perception that symptoms can be managed without health care provider intervention, and time and money savings. There are more than 80 therapeutic categories of nonprescription—or OTC—products available today. Common uses of OTC medicines include treatment of symptoms associated with the common cold, allergies, constipation, diarrhea, heartburn, mild pain, hemorrhoids, dental caries, smoking cessation, weight loss, emergency contraception, and most recently, overactive bladder control. 1 This article will review the benefi ts associated with OTC combination products surrounding cost, ease of dosing, and adherence.

Direct analysis in real time mass spectrometry with collision‐induced dissociation for structural analysis of synthetic cannabinoids

The emergence of numerous cannabinoid designer drugs has been tied to large spikes in emergency room visits and overdoses. Identifying these substances is difficult for the following reasons: (1) the compounds are novel, closely structurally related, and do not usually test positive in drug screens; (2) novel analogs rapidly appear on the market; (3) no standard protocols exist for their identification; and (4) customized and extensive sample preparation/extraction and analysis procedures are required to demonstrate their presence. Direct analysis in real time mass spectrometry (DART-MS) employing collision-induced dissociation (CID) provided confirmatory structural information that was useful in characterizing the various cannabinoid analogs, including those contained in mixtures. CID analysis illustrated that, although closely related compounds fragment in a similar fashion, their structural differences still resulted in multiple diagnostic peaks that provided additional confidence towards structural identification. DART-MS spectra were acquired under CID conditions to rapidly differentiate among five synthetic cannabinoids contained within 'herbal' products purchased locally in New York State (USA). The spectra exhibited [M+H](+) ions and product ions unique to each cannabinoid that corresponded to major structural features. Five different cannabinoid analogs, alone and as mixtures of at least two cannabinoids, were identified in six herbal products and differentiated by their CID product ion patterns. Illicit synthetic cannabinoid products continue to be readily available despite national and international restrictions. These products contain a wide range of active components, and, in many cases, multiple active ingredients. DART-MS allows rapid analyses of these synthetic cannabinoids based on the exact masses of their [M+H](+) ions and product ion peaks generated using CID.

Análisis de la sensibilidad de biotipos de Lolium multiflorum a herbicidas inhibidores de la enzima ALS, ACCasa y Glifosato

A pesar de los avances logrados en el control de las malezas con el uso de herbicidas, el manejo de las mismas no se simplificó, sino que, al contrario, surgieron nuevos desafíos, como la aparición de resistencia a herbicidas. En 2007, se reportó en Lolium multiflorum el segundo caso de resistencia a glifosato detectado en Argentina. En el sudeste de la provincia de Buenos Aires se registraron fallas de control a campo en poblaciones de Lolium multiflorum debido a su resistencia a distintos herbicidas de las familias de los inhibidores de ALS y de ACCasa y al herbicida glifosato. El objetivo de este estudio fue caracterizar el nivel de resistencia a ciertos herbicidas inhibidores de la ALS y de la ACCasa y al glifosato en una población de L. multiflorum de Lobería (Bs As, Argentina) supuestamente resistente (LmR). Se realizaron bioensayos en cajas de Petri y se determinó la GR50 mediante la variación en la longitud de coleoptile. Las curvas de dosis-respuesta se obtuvieron por medio de la ecuación log-logística. El biotipo LmR presentó resistencia múltiple a herbicidas con tres modos de acción diferentes: glifosato, inhibidores de ALS y de ACCasa. Dicho ensayo demostró la aparición de un biotipo de L. multiflorum con resistencia a múltiples principios activos.

Challenges and Opportunities in Achieving Bioequivalence for Fixed-Dose Combination Products

Fixed-dose combination (FDC) products are becoming a popular treatment option because of increased patient compliance and convenience, improved clinical effectiveness, and reduced cost to the patient, among several other reasons. A commonly applied approach for approval of a FDC product is demonstrating bioequivalence between the FDC and co-administration of individual mono-products, provided that there is adequate safety and efficacy data for co-administration of the individual agents. However, achieving bioequivalence between the FDC and individual mono-products can be very challenging, and sometimes not possible since combining multiple active ingredients, especially insoluble molecules, in a single drug product could complicate its biopharmaceutical and pharmacokinetic behavior. In this review, some of the major challenges often encountered while assessing bioequivalence during FDC development will be presented along with discussion of future opportunities to facilitate FDC development and approval.

Mosquito vector management with botanicals–the most effective weapons in controlling mosquito–borne diseases

Dear editor, Mosquito-borne diseases, viz., malaria, filariasis, dengue hemorrhagic fever, chikungunya, Japanese encephalitis etc., created huge impact on humans over the world, and the chemical insecticides remain the mainstay of effective control. But, indiscriminate and rampant use of the chemical insecticides in controlling mosquito vectors, in order to prevent diseases vectored by them, has resulted problems related to the adverse environmental effects for their (insecticides) potential toxicity, high operational cost, community acceptance, and the development of insecticide resistance among the vectors. The factors mentioned above prompted the search for new means of control strategies. Currently, the botanicals (viz., plant extracts, essential oils and phytochemicals) with mosquitocidal potential are recognized as potent alternatives to replace the synthetic insecticides in mosquito control programs due to their larvicidal, pupicidal and adulticidal properties; these also have excellent oviposition inhibiting, repellent or insect growth regulatory effects, and are found environmentally safe, degradable and target specific. Several authors, from different parts of India, timely reported the potential role of various plants extracts[1]–[4], since these contain multiple active ingredients with different modes of action, and thus lessening the chance of resistance development in mosquito populations. Govindarajan et al[1], from Tamilnadu (India), reported the ovicidal and repellent activity of Ervatamia coronaria (E. coronaria) and Caesalpinia pulcherrima (C. pulcherrima) leaf extract against Culex quinquefasciatus (Cx. quinquefasciatus), Aedes aegypti (Ae. aegypti) and Anopheles stephensi (An. stephensi), the eggs of which lost 100% hatchability due to E. coronaria, at concentrations of 250, 200 and 150 ppm, respectively, while C. pulcherrima exerted zero hatchability (100% mortality) at 375, 300 and 225 ppm, respectively against the mosquitoes. E. coronaria, which was found to have greater repellency than C. pulcherrima, provided 100% protection for 150, 180 and 210 min at 5 mg/cm2. Prabhu et al[2], from Coimbatore (India), studied the larvicidal activity of Moringa oleifera extract against larvae and pupa of An. stephensi, and recorded LC50 (57.79–78.93 ppm) and LC90 (125.93–143.20 ppm) values for larvae; the LC50 and LC90 for the pupae were 67.77 ppm and 141.00 ppm, respectively. Kumar et al[3], from New Delhi (India), nicely documented the larvicidal and repellent potential of Mentha piperita essential oil against Ae. Aegypti; the 24 h LC50 and LC90 values against the larvae were 111.90 and 295.18 ppm, respectively, and against the adults the agent showed 100% protection for 150 min. The repellent activity of Eucalyptus and Azadirachta indica (A. indica) seed oil has been evaluated against Cx. quinquefasciatus, and it has been recorded that there was zero bite for 120 and 180 min, respectively due to Eucalyptus and A. indica seed oil, and thus 100% protection from Cx. quinquefasciatus bite was achieved[4]. The botanicals might be used as an alternative to other insecticides for the control of mosquito and thus mosquito-borne diseases, and hence, such studies would be helpful in developing plant-based anti-mosquito agents. However, further investigation is required in order to quantify and determine contribution of the active ingredients, because this may lead to the discovery of novel compounds having desired mosquitocidal activities.

The Greening of Pesticide–Environment Interactions: Some Personal Observations

Background: Pesticide–environment interactions are bidirectional. The environment alters pesticides by metabolism and photodegradation, and pesticides in turn change the environment through nontarget or secondary effects.Objectives: Approximately 900 currently used commercial pesticides of widely diverse structures act by nearly a hundred mechanisms to control insects, weeds, and fungi, usually with minimal disruption of nature’s equilibrium. Here I consider some aspects of the discovery, development, and use of ecofriendly or green pesticides (i.e., pesticides that are safe, effective, and biodegradable with minimal adverse secondary effects on the environment). Emphasis is given to research in my laboratory.Discussion: The need for understanding and improving pesticide–environment interactions began with production of the first major insecticide approximately 150 years ago: The arsenical poison Paris Green was green in color but definitely not ecofriendly. Development and use of other pesticides has led to a variety of problems. Topics considered here include the need for high purity [e.g., hexachlorocyclohexane and polychloroborane isomers and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)], environmental degradation and the bioactivity of resulting photoproducts and metabolites, pesticide photochemistry (including the use of structural optimization, photostabilizers, and photosensitizers to achieve suitable persistence), the presence of multiple active ingredients in botanical insecticides, the need to consider compounds with common mechanisms of action, issues related to primary and secondary targets, and chemically induced or genetically modified changes in plant biochemistry. Many insecticides are bird, fish, and honeybee toxicants, whereas herbicides and fungicides pose fewer environmental problems.Conclusion: Six factors have contributed to the greening of pesticide–environment interactions: advances in pesticide chemistry and toxicology, banning of many chlorinated hydrocarbons, the development of new biochemical targets, increased reliance on genetically modified crops that reduce the amount and variety of pesticides applied, emphasis on biodegradability and environmental protection, and integrated pest- and pesticide-management systems.

Suppression of Monilinia Blight: Strategies for Today and Potential Fungicide Options for Tomorrow

Fungicide efficacy field trials were conducted in Nova Scotia and Prince Edward Island during the 2009 growing season to address concerns over: (i) the possible tolerance of the fungal pathogen [Monilinia vaccinii-corymbosi (Reade) Honey] causing Monilinia blight or mummy berry to presently registered fungicides; (ii) increasing scrutiny of specific fungicides by end users; and (iii) the challenge of trying to apply a curative fungicide in a timely manner after an infection period has likely occurred. Results indicated that the active ingredients propiconazole (Topas® and Orbit®), prothioconazole (Proline®), and penthiopyrad (LEM17) were very effective in suppressing Monilinia blight, tolerance to propiconazole did not appear to be present, and the use of multiple active ingredients with different modes of action and persistence also provided excellent suppression. In addition, the treatments had a profound influence on berry yield with the propiconazole, prothioconazole, and penthiopyrad treatments having berry yields that were 73.6, 111, and 112% greater than the untreated control, respectively, at the Nova Scotia site. However, these berry yield results need to be viewed with caution given the known suppressive attributes of some of these fungicides to other diseases present during Monilinia infection periods.

Development of Non-Natural Flavanones as Antimicrobial Agents

With growing concerns over multidrug resistance microorganisms, particularly strains of bacteria and fungi, evolving to become resistant to the antimicrobial agents used against them, the identification of new molecular targets becomes paramount for novel treatment options. Recently, the use of new treatments containing multiple active ingredients has been shown to increase the effectiveness of existing molecules for some infections, often with these added compounds enabling the transport of a toxic molecule into the infecting species. Flavonoids are among the most abundant plant secondary metabolites and have been shown to have natural abilities as microbial deterrents and anti-infection agents in plants. Combining these ideas we first sought to investigate the potency of natural flavonoids in the presence of efflux pump inhibitors to limit Escherichia coli growth. Then we used the natural flavonoid scaffold to synthesize non-natural flavanone molecules and further evaluate their antimicrobial efficacy on Escherichia coli, Bacillus subtilis and the fungal pathogens Cryptococcus neoformans and Aspergillus fumigatus. Of those screened, we identified the synthetic molecule 4-chloro-flavanone as the most potent antimicrobial compound with a MIC value of 70 µg/mL in E. coli when combined with the inhibitor Phe-Arg-ß-naphthylamide, and MICs of 30 µg/mL in S. cerevesiae and 30 µg/mL in C. neoformans when used alone. Through this study we have demonstrated that combinatorial synthesis of non-natural flavonones can identify novel antimicrobial agents with activity against bacteria and fungi but with minimal toxicity to human cells.

Herbal Remedies Supply a Novel Prospect for the Treatment of Atherosclerosis: A Review of Current Mechanism Studies

Atherosclerosis (AS) is a systemic cardiovascular disease with complicated pathogenesis involving oxidative stress, endothelial dysfunction and chronic inflammation. Increasing lines of evidence have questioned the statins-dominated treatment for AS, including their dangerous side-effects such as the breakdown of muscle when taken in larger doses. A multifaceted approach that addresses all major risk factors or pathological targets may provide an ideal treatment for AS. Studies of the herbal remedies on the prevention and treatment of AS have received much attention in recent years. This review summarizes some important experimental findings regarding their mechanisms of action on AS. Using the pre-set PUBMED searching syntax and inclusion criteria, representative citations published in English concerning the experimental studies of 14 herbal materials were included. We found that many extracts and (or) single compounds from these herbal materials, such as Salvia miltiorrhiza, Curcuma longa, Rheum undulatum and Panax notoginseng, could regulate multiple key targets involved in the initiation and propagation of AS. Some important findings about the effects of herbal formulations on AS were also reviewed. Given the complicated nature of AS and the holistic, combinational approach of herbal remedies, we propose that mixed herbal preparations with multiple active ingredients may be preferable for the prevention and treatment of AS. Further rigorously designed pharmacological evaluation and multi-centred clinical trials are warranted.

The importance of considering community-level effects when selecting insecticidal malaria vector products

BackgroundInsecticide treatment of nets, curtains or walls and ceilings of houses represent the primary means for malaria prevention worldwide. Direct personal protection of individuals and households arises from deterrent and insecticidal activities which divert or kill mosquitoes before they can feed. However, at high coverage, community-level reductions of mosquito density and survival prevent more transmission exposure than the personal protection acquired by using a net or living in a sprayed house.MethodsA process-explicit simulation of malaria transmission was applied to results of 4 recent Phase II experimental hut trials comparing a new mosaic long-lasting insecticidal net (LLIN) which combines deltamethrin and piperonyl butoxide with another LLIN product by the same manufacturer relying on deltamethrin alone.ResultsDirect estimates of mean personal protection against insecticide-resistant vectors in Vietnam, Cameroon, Burkina Faso and Benin revealed no clear advantage for combination LLINs over deltamethrin-only LLINs (P = 0.973) unless both types of nets were extensively washed (Relative mean entomologic inoculation rate (EIR) ± standard error of the mean (SEM) for users of combination nets compared to users of deltamethrin only nets = 0.853 ± 0.056, P = 0.008). However, simulations of impact at high coverage (80% use) predicted consistently better impact for the combination net across all four sites (Relative mean EIR ± SEM in communities with combination nets, compared with those using deltamethrin only nets = 0.613 ± 0.076, P < 0.001), regardless of whether the nets were washed or not (P = 0.467). Nevertheless, the degree of advantage obtained with the combination varied substantially between sites and their associated resistant vector populations.ConclusionProcess-explicit simulations of community-level protection, parameterized using locally-relevant experimental hut studies, should be explicitly considered when choosing vector control products for large-scale epidemiological trials or public health programme procurement, particularly as growing insecticide resistance necessitates the use of multiple active ingredients.

Stability-indicating HPLC method for simultaneous determination of terbutaline sulphate, bromhexine hydrochloride and guaifenesin

The aim of the present study was the development and subsequent validation of a simple, precise and stability-indicating reversed phase HPLC method for the simultaneous determination of guaifenesin, terbutaline sulphate and bromhexine hydrochloride in the presence of their potential impurities in a single run. The photolytic as well as hydrolytic impurities were detected as 3,5-dihydroxybenzoic acid, 3,5-dihydroxybenzaldehyde, 1-(3,5-dihydroxyphenyl)-2-[(1,1-dimethylethyl) amino]-ethanone from terbutaline, 2-methoxyphenol and an unknown impurity identified as (2RS)-3-(2-hydroxyphenoxy)-propane-1,2-diol from guaifenesin. The chromatographic separation of all the three active components and their impurities was achieved on Wakosil II column, using phosphate buffer (pH 3.0) and acetonitrile as mobile phase which was delivered initially in the ratio of 80:20 (v/v) for 18 min, then changed to 60:40 (v/v) for next 12 min, and finally equilibrated back to 80:20 (v/v) for 10 min. Other HPLC parameters were: Flow rate at 1.0 ml/min, detection wavelengths 248 and 280 nm, injection volume 10 μl. The calibration graphs plotted with five concentrations of each component were linear with a regression coefficient R2 >0.9999. The limit of detection and limit of quantitation were estimated for all the five impurities. The established method was then validated for linearity, precision, accuracy, and specificity and demonstrated to be applicable to the determination of the active ingredients in commercial and model cough syrup. No interference from the formulation excipients was observed. These results suggest that this LC method can be used for the determination of multiple active ingredients and their impurities in a cough and cold syrup.

Controlled liquid antisolvent precipitation using a rapid mixing device

Particle formation by the liquid antisolvent (LAS) process involves two steps: mixing of solution–antisolvent streams to generate supersaturation and precipitation (which includes nucleation and growth by coagulation and condensation) of particles. Uniform mixing conditions ensure rapid and uniform supersaturation, making it a precipitation controlled process where the particle size is not further affected by mixing conditions and results in precipitation of ultra-fine particles with narrow particle size distribution (PSD). In this work, we demonstrate that the use of an ultrasonically driven T-shaped mixing device significantly improves mixing of solution and antisolvent streams for precipitation of ultra-fine particles in a continuous operation mode. LAS precipitation of ultra-fine particles of multiple active pharmaceutical ingredients (APIs) such as itraconazole (ITZ), ascorbyl palmitate (ASC), fenofibrate (FNB), griseofulvin (GF), and sulfamethoxazole (SFMZ) in the size range 0.1–30 μm has been carried out from their organic solutions in acetone, dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), and ethanol (EtOH). Classical theory of homogeneous nucleation has been used to analyze the result, which suggests that higher nucleation rate results in finer particle size. Interestingly, experimental determination of degree of supersaturation indicates that higher supersaturation does not necessarily result in higher nucleation rate and nucleation rates can be correlated to solvent polarity.

The Research Progress of Antitumorous Effectiveness of Stichopus japonicus Acid Mucopolysaccharide in North of China

The sea cucumbers growing in the estuary of the Pohai of northern China are called Stichopus japonicus and are the orthodox holothurians in traditional Chinese medicine. There are multiple biological active ingredients in S. japonicus, and S. japonicus acid mucopolysaccharide (SJAMP) is one of the important ingredients. SJAMP has multiple pharmacologic actions, such as antitumor, immunologic regulation, anticoagulated blood, and antivirus. The research on antitumor has been carried out by way of animal experiments aiming at studying internal tumor-inhibiting effect of SJAMP, and the route of administration is usually peritoneal or intragastric. Additionally, sea cucumbers have been widely recognized and applied as medicated food or therapeutic prescriptions during and after the treatment of some tumors.

Rikkunshito, an Herbal Medicine, Suppresses Cisplatin-Induced Anorexia in Rats Via 5-HT2 Receptor Antagonism

Chemotherapy with an anticancer agent generally causes gastrointestinal tract disorders such as vomiting and anorexia, but the mechanism remains unclear. Rikkunshito, a kampo preparation, is known to alleviate such adverse reactions. In this study, we attempted to clarify the mechanism. We investigated the decreases of plasma acylated-ghrelin level and food intake caused by cisplatin, serotonin (5-HT), 5-HT agonists, and vagotomy as well as the decrease-suppressing effects of rikkunshito and 5-HT antagonists. In addition, binding affinities of rikkunshito components were determined in receptor-binding assays using 5-HT2B and 5-HT2C receptors. Cisplatin, 5-HT, BW723C86 (5-HT2B-receptor agonist), and m-chlorophenylpiperazine HCl (5-HT2C agonist) markedly decreased plasma acylated-ghrelin levels, although 5-HT3 and 5-HT4 agonists had no effect. In contrast, 5-HT2B and 5-HT2C antagonists suppressed the cisplatin-induced decrease of plasma acylated-ghrelin level and food intake. Administration of rat ghrelin improved the cisplatin-induced decrease in food intake. Vagotomy decreased the plasma acylated-ghrelin level, which was decreased further by cisplatin. Rikkunshito suppressed such cisplatin-induced decreases of plasma acylated-ghrelin level and food intake. The suppressive effect of rikkunshito was blocked by a ghrelin antagonist. Components of rikkunshito, 3,3',4',5,6,7,8-heptamethoxyflavone, hesperidin, and iso-liquiritigenin showed a 5-HT2B-antagonistic effect in vitro, and oral administration of rikkunshito suppressed the cisplatin-induced decrease in the plasma acylated-ghrelin level. The cisplatin-induced decreases of the plasma acylated-ghrelin level and food intake are mediated by 5-HT2B/2C receptors and suppressed by flavonoids in rikkunshito.

Treatment of mild to moderate seborrhoeic dermatitis with MAS064D (Sebclair®), a novel topical medical device: results of a pilot, randomized, double‐blind, controlled trial

MAS064D (Sebclair) is a novel steroid-free cream containing multiple active ingredients. Objective of this pilot study was to evaluate the efficacy and safety of MAS064D in the treatment of mild to moderate SD of the face. Patients (n = 60) with SD were randomized to receive MAS064D (n = 40) or a matching vehicle (n = 20). The primary study endpoint was investigators' global assessment (IGA) score at day 28, compared with baseline. Secondary endpoints included: IGA score at day 14; investigators' assessment of erythema and scaling; patients' assessment of burning/stinging, pruritus and global response to MAS064D; resort to rescue medication; quality of life. Use of MAS064D for 4 weeks was associated with a higher percentage of success in the MAS064D group than in the vehicle group (approximately 68% vs 11%, P < 0.0001). The effects of MAS064D were significantly better than those of vehicle for investigator-assessed erythema and scaling, and patients' assessed pruritus and global response to MAS064D (P 0.01). No patient in the MAS064D group required rescue medication, compared with two patients in the vehicle group. Four patients (two each in the MAS064D and vehicle groups) reported a total of six non-serious adverse events. MAS064D appears to be an effective and well tolerated cream for the treatment of mild to moderate SD of the face. Further clinical evaluation of MAS064D in SD is warranted.