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The aim of this study was to evaluate patient satisfaction and usability scores of different tape treatments and examine the scores in relation to the mechanical characteristics of the tape formulation. A questionnaire for the assessment of comfort level and satisfaction with two brand-name (Naboal, Voltaren) and four generic tapes (Yutoku, Teikoku, Rakool, Towa) containing sodium diclofenac was developed and then applied to 12 healthy volunteers. Results showed that Voltaren was difficult to apply to the skin and easier to peel off the skin than Naboal (p0.01). Moreover, Rakool was easier to peel than Naboal (p0.05). The mechanically measured peeling force was associated with pain during peeling off (r = -0.65), and the measured value of bending rigidity was associated with ease of peeling off (r = -0.97). The knowledge obtained regarding the influence of pharmaceutical properties on the degree of satisfaction with and usability of different tape formulations may be useful for supporting the selection of generic tapes tailored to individual needs or pharmacist preferences, and thus improve treatment adherence and clinical outcomes.

The detergency of special electrolytic-reduction ion water (S-100) was evaluated in comparison with typical synthetic surfactants. Furthermore, to examine the cleaning mechanism of S-100, various physicochemical characteristics of S-100 were measured and a comprehensive evaluation of cleaning was performed. S-100 (10%) had a detergency comparable to that of various surfactants, such as sodium dodecyl sulfate and sodium dodecyl benzene sulfonate, which are generally blended or mixed in residential detergents. In addition, concentrated aqueous solutions of 10% or more of S-100 showed stronger detergency. The cleaning mechanism of S-100 is mainly attributed to the effect of surface tension reduction due to dissolved hydrogen or hydrogen nanobubbles in S-100, and the alkalinity generated by electrolysis charged the surface of the dirt or adherend, resulting in a peeling effect.

Background Intravenous (IV) infusions of volatile anesthetics in lipid emulsion may increase blood lipid concentration, potentially altering the anesthetic agent's blood solubility and blood-gas partition coefficient (BGPC). We examined the influence of a low-lipid concentration 20% sevoflurane emulsion on BGPC, and the anesthetic potency of this emulsion using dogs. Methods We compared BGPC and anesthetic characteristics in 6 dogs between the IV anesthesia of emulsion and the sevoflurane inhalation anesthesia in a randomized crossover substudy. Minimum alveolar concentrations (MACs) were determined by tail-clamp stimulation by using the up-and-down method. Blood sevoflurane concentration and partial pressure were measured by gas chromatography; end-tidal sevoflurane concentration was measured using a gas monitor. The primary outcome was BGPC at the end of IV anesthesia and inhalation anesthesia. Secondary outcomes were time to loss/recovery of palpebral reflex, finish intubation and awakening, MAC, blood concentration/partial pressure at MAC and awakening, correlation between blood partial pressure and gas monitor, and the safety of emulsions. Results BGPC showed no difference between IV and inhaled anesthesia (0.859 [0.850-0.887] vs 0.813 [0.791-0.901]; P = .313). Induction and emergence from anesthesia were more rapid in IV anesthesia of emulsion than inhalation anesthesia. MAC of emulsion (1.33% [1.11-1.45]) was lower than that of inhalation (2.40% [2.33-2.48]; P = .031), although there was no significant difference in blood concentration. End-tidal sevoflurane concentration could be estimated using gas monitor during IV anesthesia of emulsion. No major complications were observed. Conclusions IV anesthesia with emulsion did not increase the BGCP significantly compared to inhalation anesthesia. It was suggested that the anesthetic potency of this emulsion may be equal to or more than that of inhalation.

We compared the pharmaceutical properties, such as surface tension, drop volume, nozzle inner diameter, and force to push the drug product out of the container (squeeze force), of purified sodium hyaluronate eye drops preparations of one brand-name (Hyalein) and 11 generic drugs used for treatment of keratoconjunctiva epithelial disorders, and examined product selection based on the needs of the patient. The surface tension of Nissin (51.0 dyn/cm) and Nitten (52.3 dyn/cm) was significantly lower than that of Hyalein (62.8 dyn/cm), whereas Nitten PF (69.5 dyn/cm) was significantly higher than Hyalein. The drop volume of Tearbalance (42.4 mg), Nissin (43.7 mg), and Nitten (42.7 mg) was significantly lower than that of Hyalein (50.4 mg). We compared the squeeze force using a wearable touch sensor (Haptic Skill Logger: HapLog®) and digital force gauge (DF). The squeeze force of HapLog® showed values of about 1.7- to 3.5-fold higher than that of DF. Moreover, the squeeze force of Eyecare (34.0 N), Kyorin (35.4 N), and Nitten PF (44.3 N) by HapLog® was significantly higher than that of Hyalein (10.5 N). In contrast, the squeeze force of Kyorin (20.8 N) and Nitten PF (25.0 N) by DF was significantly higher than that of Hyalein (12.2 N). Two questionnaire surveys on the feeling of instillation of eye drops revealed a strong negative correlation between feeling of use and squeeze force.

The inhibitory activity of electrolyzed reduced water (ERW) against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which is the etiological agent responsible for coronavirus disease 2019 (COVID-19), was tested in vitro on Vero E6 cells using a plaque assay. Infectious virus titers of cells treated with ERW 100%, 50% and 33.3% solutions and phosphate buffered saline (PBS, negative control) and exposed to the virus suspension for 60 seconds were 2.25, 2.65, 3.21 and 7.38, respectively. ERW has a high pH and low surface tension. It is considered that the alkaline property of ERW breaks down phospholipids and proteins of envelopes. The role of pH and reducibility on the virucidal effect of ERW should be further evaluated. This study provides a foundation for utilizing ERW as an effective antiviral aqueous solution in a variety of applications.

Tape products containing ketoprofen have transdermal analgesic and anti-inflammatory effects. We compared the physicochemical properties (water-vapor permeability, peel force, peel force-time curve) between one brand-name product and eight generic products. Regarding the measurement of water-vapor permeability, the formulations using methacrylic acid n-butyl acrylate copolymer (MBA) adhesives showed higher water-vapor permeability than those using styrene isopropyl styrene block copolymer (SIS) adhesives. In the case of the formulation using SIS adhesive, the central part of the formulation had higher water-vapor permeability than both ends. In the 90-degree peel test using the methods of adhesion testing, significant differences were observed between the products, especially as the various application times (5 min, 30 min, 9 h and 24 h) increased. This may be because the longer the time of attachment to the adherend, the more the adhesive force with the adherend increased due to the "anchoring effect" of the adhesive. The measurement of the peel force-time curve showed different curves among the products, especially in the peel force curve of Teikoku after 24 h, which showed two characteristic peak curves. Furthermore, when the peel forces at 25°C and 40°C were compared, Mohrus and Toko showed significantly higher values at 40°C compared to 25°C. This study showed that there are many generic drugs with formulation characteristics different from those of brand-name drugs, and that there is a large difference among the products in terms of adhesion and detachment.

We compared the pharmaceutical properties, such as surface tension, drop volume, nozzle inner diameter, and force to push the drug product out of the container (squeeze force), of purified sodium hyaluronate eye drops preparations of one brand-name (Hyalein) and 11 generic drugs used for treatment of keratoconjunctiva epithelial disorders, and examined product selection based on the needs of the patient. The surface tension of Nissin (51.0 dyn/cm) and Nitten (52.3 dyn/cm) was significantly lower than that of Hyalein (62.8 dyn/cm), whereas Nitten PF (69.5 dyn/cm) was significantly higher than Hyalein. The drop volume of Tearbalance (42.4 mg), Nissin (43.7 mg), and Nitten (42.7 mg) was significantly lower than that of Hyalein (50.4 mg). We compared the squeeze force using a wearable touch sensor (Haptic Skill Logger: HapLog

We investigate the compositions of vesicle formulation by assembling phase diagrams of the ternary components of lauroyl-glutamyl-lysil-lauroyl-glutamate (C12-GLG-C12) peptide-based gemini-type amphiphile/citric acid/water using visual and microscopic observations. To clarify interactions between C12-GLG-C12 and citric acid, turbidity and zeta potential of the mixtures were investigated. To improve the stability of metastable vesicles, appropriate additives were examined by measuring particle size and zeta potential, visual observation and transmission electron microscopy. The turbidity increased and the absolute value of zeta potential decreased with increasing citric acid concentration in C12-GLG-C12/citric acid solutions. Then, a metastable γ region having vesicles was formed. The stability of vesicles increased with increasing cholesterol concentrations. This result suggests that a coacervation has occurred due to the effective cross-sectional area decreasing with increasing C12-GLG-C12 hydrophobicity, which was derived from inhibition of the carboxyl group dissociation. Furthermore, we hypothesized that the orientation of cholesterol between vesicle membranes is a contributing factor to improve the vesicle stability. From transmission electron microscopic observations, it was made clear that the vesicles consisting of cholesterol and C12-GLG-C12 at a molar ratio of 2:1 showed multilayered structures. The vesicles consisting of C12-GLG-C12, cholesterol and citric acid are expected to be used as transdermal drug delivery system carriers, as they can be easily prepared using biocompatible compounds without the use of organic solvents such as chloroform.

With respect to diclofenac sodium-containing tape preparations of nonsteroidal antiphlogistic drug, we compared the pharmaceutical properties (pH, elongatedness, water-vapor permeability, adhesive force, and peeling-force) of 11 medicinal drugs (2 brand-name and 9 generic drugs) to obtain evidence for product selection in line with the needs of the patient. The elongatedness of the generic drugs Teikoku (1.39), Yutoku (1.40), and Nippon-zoki (1.43) were significantly higher than the brand-name drug Voltaren® (1.22). The adhesive force was measured using the probe tack test and the inclined ball tack test. The probe tack test results of Naboal® (6.8 N/cm2), Teikoku (6.1 N/cm2), Yutoku (5.9 N/cm2), Nippon-zoki (6.2 N/cm2), and Rakool (6.2 N/cm2) were higher than that of Voltaren (2.0 N/cm2). The inclined ball tack test results of Naboal (18.0), Teikoku (24.0), Yutoku (21.5), and Nippon-zoki (22.7) were also higher than that of Voltaren (7.2). Concerning peeling-force measurement, the 90° peeling-forces of Naboal (0.95 N), Teikoku (0.96 N), Yutoku (0.94 N), and Nippon-zoki (1.01 N) were higher than that of Voltaren (0.68 N). These results show that there were marked differences in the feeling of use of each product between the brand-name and generic drugs. The pharmacist indicates the basis for selection of a preparation according to the feeling of use desired by each patient. It has become possible to recommend products suitable for each patient, which will allow pharmacists to provide products according to the needs of each patient when a brand-name drug is changed to a generic one.

The mean diameter of emulsion droplets prepared using three different emulsifiers (egg yolk lecithin alone, egg yolk lysolecithin alone, and a mixture of egg yolk lecithin and lysolecithin) was investigated. Considering the nasal administration of enteral nutrients or that through gastric/jejunal fistulae, the stability of each emulsion with artificial gastric fluid (pH 1.2) or intestinal fluid (pH 6.8) was investigated. When adding artificial intestinal fluid, all emulsions prepared with various emulsifiers (egg yolk lecithin, egg yolk lysolecithin, soybean lecithin, soybean lysolecithin, DK ester® F-140, and Sunsoft® A-141E) were stable. On the other hand, when adding artificial gastric fluid, emulsions prepared with egg yolk lysolecithin or Sunsoft® A-141E were stable, but there was a reduction in the stability of emulsions prepared with the other emulsifiers, with an increase in the particle size. Based on these results, we prepared an emulsion using a natural component-derived emulsifier for ...

The physicochemical properties (pH, yield value, and squeeze force) of a drug for dermatomycosis, a terbinafine hydrochloride-containing cream (a brand-name product), and 12 over-the-counter drugs (OTCs) were measured and compared to ascertain the characteristics of each product. The pH of the brand-name product, Lamisil, was 4.1, and that of the OTC products ranged from 4.2 to 7.6; Lamisil Plus (7.6) had a significantly higher pH. Moreover, the yield value for Lamisil, as an index of cream ductility, was 128 dyn/cm2, and that for the OTC products ranged from 110 to 887 dyn/cm2. In particular, the OTC products Damalin (887 dyn/cm2), Barriact (512 dyn/cm2), and Exiv Deep (663 dyn/cm2) had a significantly higher yield value. In addition, the squeeze force was measured by attaching a HapLog® to the thumb and second finger. The squeeze force for Lamisil was 12.9 N, and that for the OTC products ranged from 1.8 to 14.6 N. The OTC product Bilumon (1.8 N) had a significantly lower squeeze force. These results indicated that there were marked differences in the pharmaceutical properties of brand-name and OTC products. External preparations are characterized by their feel during use. Based on the current results, the pharmaceutical characteristics of drugs resulted in differences in their feel during use, suggesting that products appropriate for individual patients can be recommended.

We measured and compared the physicochemical properties (pH, yield value, and squeeze force) of a drug for dermatomycosis, terbinafine hydrochloride-containing cream (brand-name product), and 12 generic products to clarify the characteristics of each product. On pH measurement, the pH value of the brand-name product, Lamisil, was 4.8, and those of the generic products ranged from 4.3 to 5.5, showing no marked difference. Furthermore, the yield value of Lamisil, as an index of cream ductility, was 122.2 dyn/cm2, and those of the generic products ranged from 42.1 to 1,621.5 dyn/cm2. In particular, the value of a generic product, Taiyo (42.1 dyn/cm2), was significantly lower, whereas that of another one, Viras (1,621.0 dyn/cm2), was significantly higher. In addition, the squeeze force was measured by attaching a HapLog® to the thumb and second finger. The value of Lamisil was 12.9 N, and those of the generic products ranged from 8.0 to 15.4 N. The values of generic products, Mylan (8.6 N), Tebinaceil (9.0 N), and Kelger (8.0 N), were significantly lower, whereas that of another one, Viras (15.4 N), was significantly higher. These results showed that there were marked differences in the pharmaceutical properties between the generic and brand-name products. The above pharmaceutical characteristics of drugs facilitated the presentation of reasons for differences in the sense of use, which characterizes external preparations, suggesting that products appropriate for individual patients can be recommended.

The pH, osmotic pressure (cryoscopy), viscosity, squeeze force, spray angle, and spraying frequency of nasal spray containing ketotifen fumarate (1 brand-name product and 8 generic products) were measured. Based on the results of pH measurement, all products were weakly acidic (4.0 to 5.1). For all products, the osmotic pressure ratio to physiological saline was approximately 1. The viscosity of various products ranged from approximately 1.0 to 1.5 mPa·s. The spray angle of drug solution differed among the products: minimum, 46 degrees (Sawai and Fusachol); and maximum, 68.7 degrees (Sekiton). In particular, TOA, Sawai, Fusachol, and TYK showed significantly smaller angles compared to Zaditen (brand-name product). Container properties varied among the products: minimum squeeze force, 19.0 N (Sekiton); and maximum squeeze force, 43.1 N (Sawai). Based on these results, although all the above products are identical in dosage form and active ingredient, the differences in pharmaceutical properties, such as container operations and drug-solution spraying/attachment, may markedly influence patients' subjective opinions.

We measured the pH, water-vapor permeability, adhesive force, peeling-force, elongation rate, support flexibility, and peeling time of medicinal and over-the-counter (OTC) tape preparations containing felbinac. When measuring the pH of each preparation, Felnabion (pH 4.5) was weakly acidic, and EMEC and Tokuon (pH 7.0) were neutral. When measuring the water-vapor permeability of each preparation, that of a generic product, EMEC (380 g/m2/24h), was twice as high as that of a brand-name product, Seltouch (189 g/m2/24 h). The adhesive force was measured using the ball tack test. The adhesive forces of OTC drugs, Salomethyl, Homepass, and Tokuhon (1.04 g), were higher than that of Seltouch (0.06 g). Concerning peeling-force measurement, the peeling-forces of a generic product, Falzy (4.15 N), and an OTC drug, Omuneed (4.89 N), were higher than that of Seltouch (0.91 N). The elongation rates of a generic product, Sumilu (319%), and OTC drugs, Nabolin (298%) and Homepass (299%), were higher than that of Seltouch (251%), but that of Tokuhon (72%) was lower. The support flexibilities of EMEC (150 degrees) and Tokuhon (131 degrees) were higher than that of Seltouch (96 degrees). In addition, the peeling time of Seltouch was 120 min or more, whereas those of EMEC and Nabolin were 1.4 and 0.2 min, respectively. These results suggest that the differences in pharmaceutical properties, such as the pH, water-vapor permeability, adhesive force, peeling-force, elongation rate, support flexibility, and peeling time, among the preparations markedly influence patients' subjective comfortableness. The results of this study facilitated individuals' comfortableness-matched drug selection.

This study was conducted in order to establish a health management method for the elderly in a community through follow-ups of bone mineral density (BMD) measurement results over a 1-year period based on BMD measurements performed by pharmacists and a guidance program. Regarding BMD measurement results, the percent young adult mean (%YAM: mean BMD in healthy persons of the same sex aged between 51 and 82 years old) significantly increased in Period I, during which the intervention by pharmacists was performed (6 months after the start of measurements), but significantly decreased in Period II, during which this intervention was not performed (between 7 and 12 months after the start of measurements). Based on these results, lifestyle improvements were effective in Period I regardless of sex or age; however, it may be important to maintain an improved diet and subject motivation in the future. The results of this study suggest that community pharmacists play an important role in community medicine through positive intervention for local residents' health support.

Ternary phase diagrams of gelatin-water-methanol, gelatin-water-ethanol, and gelatin-water-propanol systems were prepared to evaluate optimal coacervation. The results of their evaluation suggested that the optimal coacervation region expands with the hydrophobicity of the added poor solvent (methanol, ethanol, 1-propanol, and 2-propanol). Microcapsules prepared based on the optimal coacervation region differed in controlled drug release among poor solvents used even when the concentration of gelatin, a membrane component, is the same. Compared with microcapsules prepared using the gelatin-water-ethanol system, those prepared using the gelatin-water-propanol system showed a 34% decrease in the drug release rate 24h after the initiation of the drug release test. These results suggested that microcapsules prepared using gelatin-water-various lower alcohol systems can readily control drug release and can be a useful drug delivery system (DDS).

The presence/absence of adsorption of 9 representative types of antimicrobial agent used in combination with a polymyxin-B immobilized fiber (PMX-F) were determined and the degree of adsorption to PMX-F was quantitatively evaluated. Various antimicrobial agents were dissolved at appropriate concentrations, and PMX-F was added to each solution and incubated at 37°C. Antimicrobial solutions without PMX-F were also similarly incubated as controls. After 2 and 4h, the concentration of each antimicrobial agent was determined using HPLC. To produce an environment closer to the in vivo state, albumin or serum was added, and similar evaluation was performed. In the presence of albumin, the rate of adsorption to PMX-F was relatively high for Cefmetazon(®), Pentcillin(®), Ciproxan(®) and Zyvox(®). In the presence of serum, the adsorption rate was 4.02±2.83% for Pentcillin(®), 5.59±1.00% for Ciproxan(®), and 22.12±3.23% for Zyvox(®). The results of this study suggest that adequate caution is necessary on the clinical use of Zyvox(®), which was adsorbed in the presence of serum as an environment close to the in vivo environment, but the use of other antimicrobial agents in combination with PMX-F may have only slight influences on adsorption to PMX-F.

As typical periodontopathic bacteria, Porphyromonas gingivalis (P. gingivalis) and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) were exposed to electrolyzed ion-reduced water (ERI) and ERI containing 1% sodium carboxymethylcellulose (CMC-Na) (ERI-1% CMC-Na), and the time course of their bactericidal action was evaluated. More than 99% of each bacteria species were killed after exposure to each solution for 15 sec. In addition, 1% CMC-Na, which was added to prolong bactericidal action, did not affect the bactericidal action of ERI. Its bactericidal action was concentration-dependent. No viable P. gingivalis bacteria were observed at a concentration of 15% of the undiluted solution and no viable A. actinomycetemcomitans bacteria were observed at a concentration of 50%, indicating differences in the bactericidal action of ERI for the two bacteria species. These results suggest that ERI may be extremely useful in preventing and treating periodontal diseases.

We examined the pharmacokinetics of edaravone when edaravone/hydroxypropyl-β-cyclodextrin (HPβCD) complex solution, including L-cysteine (L-Cys) and sodium hydrogen sulfite (SHS), was administered intravenously, rectally and via the oral mucosa. In oral mucosal administration, atomized edaravone/HPβCD complex solution that contained L-Cys and SHS was sprayed into the mouth of Wistar rats. Oral mucosal and rectal administration of edaravone/HPβCD complex solution that contained L-Cys and SHS was compared with that for edaravone/HPβCD complex solution without L-Cys and SHS. When edaravone 0.25–1.0 mg was administered intravenously, C₀ and AUC0–60 were linear. In oral mucosal and rectal administration, Cmax and AUC0–60 of edaravone/HPβCD with L-Cys and SHS were significantly higher than those of edaravone/HPβCD without L-Cys and SHS. On the other hand, bioavailability of oral mucosal, rectal and oral administration was about 100, 63.5 and 26.6%, respectively. This study suggested that L-Cys and SHS were useful for the oral mucosal and rectal administration of edaravone.

We produced gels using electrolytic-reduction ion water and magnesium aluminum silicates (smectone), and evaluated in detail gel properties in the presence of various types of salt (NaCl, KCl, CaCl(2), MgCl(2), and AlCl(3)). Each salt was added to deionized-distilled water or electrolytic-reduction ion water, and phase diagrams for the smectone concentration (2.0-4.0%) were produced. The areas of the three phases of smectone (gel, sol, and separation) at each salt concentration were expressed as percentages of the total area. As a result, uni- and polyvalent cations (excluding Ca(2+) ions) affected the stability of gels produced using electrolytic-reduction ion water, and, particularly, univalent cations (Na(+), K(+)) markedly improved gel stability. Using electrolytic-reduction ion water as a dispersal medium, drug delivery systems (DDS) that can maintain the gelling state can be prepared. Thus, gel preparations with maintained functions or controlled-release transdermal drugs can be obtained.

We examined the effects of metabolic inhibitors on skin permeation of edaravone. SKF-525A, diclofenac sodium (DIC) and indomethacin (IND) were added to supernatant fluid (SF) of hairless rat (HR) skin homogenate. L-Cysteine (L-Cys) and benzotriazole (BTA), as pharmaceutical additives, were added to HR skin homogenate SF, and incubated at 37 degrees C for 30 min. K(m) and V(max) values were calculated. For determination of edaravone skin permeation from edaravone/hydroxypropyl-beta-cyclodextrin (HPbetaCD) complex solution, HR skin was placed in a Franz diffusion cell, and kept at 37 degrees C. Edaravone/HPbetaCD solution that contained L-Cys was put into the donor side. The relative activity in skin homogenate SF after co-treatment with IND and SKF-525A decreased to 40.8% of the control. However, DIC and IND had a weak inhibitory effect. For inhibition of edaravone metabolism, L-Cys and BTA had no effect on K(m) value, but V(max) was significantly decreased compared with controls (*P

The stochastic properties of the daily variations in drug sales at a community pharmacy in the season of 2004/2005 are studied by a factor analysis. The four factors which can closely be related to chronic diseases, common cold, influenza and allergies are extracted fro mt hedata of 31 drugs. For most of the drugs, the sales time series can approximately be represented by the four factors alone. Similar results are obtained from the same pharmacy in the 2003/2004 season and also from two other pharmacies. Interestingly, the classification of drugs according to the factor analysis corresponds to their medicinal actions.

We investigated the skin metabolism of edaravone as a radical scavenger in Wistar and hairless rat skin. Approximately 1 g of abdominal skin was excised from 10-week-old Wistar and hairless rats, homogenized in 10 ml saline, and centrifuged at 10000 g for 20 min. The supernatant fluid was used for the examination of edaravone metabolism in the skin, and we also used supernatant fluid that was heated at 80 degrees C. Edaravone solution (0.05 ml, 2.4 micromol/ml) was added to 0.95 ml Wistar rat and hairless rat skin homogenate supernatant fluids. In Wistar rats, the residual amount of edaravone in skin homogenate supernatant fluid at 37 degrees C after 0, 5, 10, 20 and 30 min was 61.58+/-1.65, 41.84+/-8.52, 35.54+/-8.62, 19.73+/-5.99 and 13.89+/-4.40%, respectively. In hairless rats, the residual amount of edaravone in skin homogenate supernatant fluid at 37 degrees C after 0, 5 and 10 min was 50.19+/-14.17, 6.71+/-5.82 and 0.89+/-0.80%, respectively, and edaravone was not detected after 20 min. Although it was thought that metabolic enzyme activity in skin homogenate supernatant fluid was lost following heat treatment at 80 degrees C, the residual amount of edaravone in our skin homogenate supernatant fluid decreased with time. It is suggested that edaravone metabolism in the skin is necessary for non-enzymatic reactions.

Since early morning hypertension is closely related to cardiovascular risks,the regular measurement of blood pressure is very important.In the present study,we performed a questionnaire survey of 443 patients taking depressors regarding possession of a home sphygmomanometer,explanation received when it was purchased,status of its use,and awareness of hypertension.The survey was performed at the time medicines were administered by pharmacists in the outpatient department.Of the patients surveyed,330 had a home sphygmomanometer,but only about 33% of them used it on a daily basis.Evaluation by the F test suggested that the patients who used a home sphygmomanometer daily were well informed about hypertension,while those who rarely used it knew less about hypertension.This suggests that the frequency of blood pressure measurement using a home sphygmomanometer varies with the amount of knowledge of the disease,and that it is important make patients receiving depressors more aware of the disease they have.

The aim of this paper is to compare the geographical routes and speeds of influenza propagation in and around Tokyo, including Kanagawa, Saitama, Tochigi and Fukushima prefectures, in the seasons of 2003/2004, 2004/2005 and 2005/2006. Each season ranges from November 1st to October 31st. The propagation pattern is estimated from the daily variations in the sales amount of anti-influenza drug at about 30 pharmacies in the area. The time lags (day) of influenza infection periods between distant pharmacies are calculated by the cross-correlation functions of the drug sales at the pharmacies. We conclude that the influenza infection spread from the urban area of Tokyo to its suburbs (Saitama and Kanagawa) along the railway systems in all the seasons examined. However, no definite infection routes can be found in Tochigi and Fukushima. The infection periods of adults are contrasted with those of children in individual observation sites.

Halogenated volatile anesthetics can be safely and rapidly administered to animals and humans using emulsion formulations. However, they must be administered simultaneously with a high dose of lipids. Increasing the concentration of volatile anesthetics may solve this clinical issue. Moreover, careful observation is needed when the emulsion is injected because anaphylactic reactions have been reported.We prepared a 20% sevoflurane lipid emulsion and administered it to 69 male Sprague-Dawley rats via the tail vein. The median effective dose (ED50) for the loss of righting reflex and the median lethal dose (LD50) were determined. ED50 and LD50 values were calculated using nonlinear regression, and data were fitted with a cumulative Gaussian model using GraphPad Prism. Measurements of vital signs and evaluation of the presence of adverse effects associated with continuous infusion of emulsions were verified. Stability of the emulsion was assessed by measuring particle size at 365 days and sevoflurane concentrations after opening the vial at 180 minutes.The ED50 and LD50 were 0.47 mL/kg (95% confidence interval [CI], 0.46-0.48) and 1.13 mL/kg (95% CI, 1.07-1.18), respectively. The therapeutic index (LD50/ED50) was 2.41 (95 CI%, 2.23-2.59), which compares favorably with therapeutic index of a fluoropolymer-based emulsion of sevoflurane, propofol, and thiopental. There were no adverse effects associated with the continuous infusion of emulsions. Particle size of the emulsion at 365 days after preparation was 78.9 ± 3.8 nm (±SD), and sevoflurane concentration at 180 minutes after opening the vial was 19.0% ± 0.6% (±SD).We prepared a 20% sevoflurane lipid emulsion using caprylic triglyceride (i.e., medium-chain triglyceride). In rats, this emulsion was an effective anesthetic and was not associated with adverse events. The emulsion was stable after consecutive evaluation for 365 days and for 180 minutes after the vial was opened.

The cross-correlation functions between the time series of drug sales at community pharmacies have been used for the epidemiological understanding of influenza propagation process. The aim of this paper is to examine the methods of smoothing for determining the maximum position (time lag) of the cross-correlation function. The moving average method with a window of seven days is taken to eliminate the hebdomadal frequencies originating from the life style of people around the pharmacies, or rather, purchasers. Based on the smoothed data of influenza anti-viral agents for adults and children at pharmacies in Tokyo and its vicinity, this paper tries to give an answer to the question of which are earlier infected with influenza, adults or children, in the limited areas.

Here we show a quantitative, spatial interpretation of influenza propagation process in Tokyo and its environs in the season from November 1st, 2004 to October 31st, 2005. The time lags (day) of influenza propagation between distant sites are calculated by the cross-correlation functions of the daily variations in the amount of drug sale at community pharmacies. The influenza infection appears to have spread from the urban area of Tokyo to its suburbs in the season of 2004-05. From the time lags and distances of the pharmacy locations, the mean propagation speed is estimated to be 3.5 km/day.

The characteristics of mixed phospholipids were examined when used as dispersing agents and emulsifiers. Synthesized phospholipids were mixed to investigate the potential effects of different hydrophilic or lipophilic groups on emulsification and dispersion. To examine the effects of the hydrophilic polar head group on the dispersing or emulsifying potency of phospholipids, l-alpha-phosphatidylcholine dimyristoyl (DMPC) and l-alpha-phosphatidylethanolamine dimyristoyl (DMPE) were mixed in various ratios. Moreover, all combinations of two kinds of phosphatidylcholines (PCs) out of l-alpha-phosphatidylcholine dilauroyl (DLPC), DMPC, l-alpha-phosphatidylcholine dipalmitoyl (DPPC) and l-alpha-phosphatidylcholine distearoyl (DSPC) were tested (50:50, w/w) to examine the effects of the hydrophobic carbon chains on the dispersing or emulsifying potency of phospholipids. Mean diameters of vesicles and O/W emulsions prepared by sonication were measured. Vesicles prepared with DMPC-DMPE mixtures gave larger particle sizes than those of DMPC alone. Particle sizes of vesicles prepared with a mixture of two kinds of PCs increased when adding a PC with a longer carbon chain, while particle sizes in a mixture with a PC having a shorter carbon chain was comparable to those in pure PC. In vesicles that were generated by hydration of phospholipids and had a bilayer form, the physical form of the phospholipids consisting of bilayers was thought to be an important factor influencing particle sizes. Among the emulsions, DMPC-DMPE mixtures gave a similar droplet size to DMPC alone. Droplet size in emulsions prepared with a mixture of two kinds of PCs had a strong positive correlation with the total number of carbons, which corresponds to hydrophilic-lipophilic balance (HLB). In O/W emulsions, in which phospholipids were absorbed at water-oil interfaces and which have a single layer form, HLB was thought to be a major factor in the determination of particle size; likewise with non-ionic emulsifiers.

We investigated characteristics of various phosphatidylcholines (PCs) used as dispersing agents and emulsifiers. Six PCs with different lengths of acyl hydrocarbon chains and different degrees of unsaturated acyl hydrocarbon chains were selected to examine influences of a lipophillic part of phosphatidylcholines in emulsion and dispersion systems. Vesicles and oil-in-water emulsions were prepared by sonication under several ambient temperature conditions. Mean diameters of vesicles and oil droplets in emulsions were measured by a submicron particle sizer. In vesicles that are generated by hydration of the PCs and have a bilayer form, particle size was influenced by length and degree of unsaturation of acyl hydrocarbon chains of a PC. PCs with shorter acyl hydrocarbon chains or unsaturated bonds are considered more potent dispersing agents. Preparation temperature of the PC is also a factor affecting potency of dispersion. In O/W emulsions in which PCs were absorbed at water–oil interfaces and which have a single layer form or liquid-crystal layer form, particle size was also influenced by length and degree of unsaturation of acyl hydrocarbon chains of a PC. PCs with shorter and saturated acyl hydrocarbon chains are considered more potent emulsifiers. Unsaturation of acyl hydrocarbon chains weaken the ability of emulsification due to vulnerable double bonds. For stable emulsions, it is considered beneficial for PCs to form small oil droplets and lamellae liquid-crystal phase. From this perspective, saturated PCs with short hydrocarbon chains, i.e., DLPC and DMPC, may have advantages in preparing a stable emulsion not only by giving a smaller droplet size but also by forming lamellae liquid-crystal phase. When considering characteristics of PCs as emulsifiers, their characteristics as dispersing agents is also useful information.

Hemolysis caused by the interaction between rabbit erythrocytes and oil-in-water emulsions (e.g., fat emulsions or drug carrier emulsions for intravenous injections) prepared with various oil concentrations was investigated. In emulsions prepared with oil concentrations in the range of 2.5-12.5%, the percentage of both hemolysis and free purified egg yolk lecithins (PEL) in the water phase of the emulsions decreased with the increased oil concentration and became constant above 12.5% oil concentration. The change in free PEL percentage in the water phase of the emulsions prepared with various oil concentrations showed the same relationship as that of the percentage hemolysis caused by the interaction between rabbit erythrocytes and emulsions prepared with various oil concentrations. No hemolysis caused by an interaction between rabbit erythrocytes and vesicles prepared with PEL at a concentration of 0.012% was observed. However, hemolysis levels of 64.2% and 91.1% were observed at PEL concentrations of 0.12% and 1.2%, respectively. These results led to the conclusion that hemolysis caused by the interaction between erythrocytes and emulsions was due to PEL vesicles in the water phase of the emulsions.

The formation of higher order aggregates in aqueous media from naturally occurring surfactants (biosurfactants) and its mechanism have been studied. A liposome (vesicle), as a kind of artificial cell, is prepared according to a newly developed microencapsulation technique from phospholipids by mimicking the molecular structure of biomembranes. Secondly, the surface active properties of alkaline salts of spiculisporic acid depend on the kinds of alkali as its gegen ions; these have been studied for the purpose of a detailed understanding of vesicle formation of the alkylamine salts of spiculisporic acid in the binary system consisting of spiculisporates and water. Thirdly, the solution behavior of the ternary system of spiculisporates-oil-water is examined. Divalent cationic salts of spiculisporic acid formed oil-in-water (O/W) emulsion gels due to ionic-bonding network formation of spiculisporates around emulsified oil droplets and these are important for their gelling properties. These gelling systems ma...

We performed a systematic review of the effectiveness of anti-emetics for prophylaxis of cisplatin-induced delayed emesis using meta-analysis. We selected 12 reports of randomized controlled trials from MEDLINE (1966-2003. 4) and The Cochrane Library Issue 1, 2003. Nine of these reports were evaluated as high quality and the others as low quality according to the evaluation criteria of Jadad et al., and only the high-quality reports were subjected to meta-analysis. The statistical results obtained from all 12 reports were also compared with those obtained from the 9 reports of high quality. Corticosteroids significantly reduced the occurrence of delayed emesis. Metoclopramide tended to reduce the occurrence of delayed emesis, although not to a significant extent. In contrast, 5-HT3 receptor antagonists did not show a significant prophylactic effect on delayed emesis. Combination treatments using corticosteroids with metoclopramide or 5-HT3 receptor antagonists did not show significant additional benefits over corticosteroids alone. In conclusion, treatment with corticosteroids without additional metoclopramide or 5-HT3 receptor antagonists appears to be preferable for the prevention of delayed emesis induced by cisplatin.

The composition of vehicle on the reversible sol-gel transition temperature in a ternary system made up of methylcellulose (MC), polyethylene glycol (PEG), and citric acid (SC) was investigated. The properties of the in situ gelling system were estimated by rheological measurement. When PEG (4000) concentration was varied from 0% to 10% while MC (SM25) and SC concentrations were kept constant at 1.5% and 3.5%, respectively, the reversible sol-gel transition temperature lowered from 38 °C to 26 °C with increasing PEG concentration. However, the extent of lowering in temperature was not influenced by the molecular weight of PEG. The reversible sol-gel transition temperature shifted towards the lower temperature with increasing MC concentration, and towards the higher temperature with decreasing pH. Comparison of rheological properties between the present thermo-setting in situ gelling solution and a conventional one, such as gellan gum solution or Poloxamer 407 solution, revealed that the present solution radically differed from the conventional solutions in the incipient gelling mechanism. These findings suggest that the ternary system in this study would be useful as a drug delivery system for instillation of drugs into the eye.

We examined hydrogenated purified egg yolk lecithins, having practical advantages over non-hydrogenated ones, as liposomal membrane materials. Liposomes were prepared by the microencapsulation vesicle (MCV) method in which liposomes are formed through two-step emulsification and dispersion. Three types of purified egg yolk lecithins with different iodine values were examined after being dissolved in one of three lipid solvents. The liposome size increased as the temperature during the second emulsification increased, being closer to the boiling temperature of the solvent. The preparation temperature in relation to the transition temperature of each lecithin was also a factor affecting liposome sizes. As for the encapsulation efficiencies of the model compound calcein in liposomes, they differed mainly depending on the solubility of each lecithin in a lipid solvent and it was more obvious in hydrogenated lecithins. A high preparation temperature resulted in lower encapsulation efficiencies, suggesting that leakage of encapsulated calcein was facilitated at high temperature in the MCV methods. There was a significant correlation between liposome sizes and encapsulation efficiencies in non-hydrogenated purified egg yolk lecithin but not in hydrogenated ones. When using hydrogenated purified egg yolk lecithins as liposomal membrane materials, it was suggested that a lipid solvent should be chosen so that a lecithin completely dissolves under the preparation condition in order to achieve a higher encapsulation efficiency. Smaller liposome particles were obtained when the second emulsification was performed at a lower temperature compared with the boiling point of the lipid solvent. These findings can be applied to control encapsulation efficiencies and particle sizes in each particular liposome preparation enclosing therapeutic agents.

The effect of alcohol and electrolytes on simple coacervation in the phospholipid−water−alcohol system is described in detail. The optimal coacervation conditions for formation of lipid vesicles in the phospholipid−water−alcohol system were examined by the triangular phase diagram. Three different alcohols, methanol, ethanol, and 1-propanol, were used as a lipid solvent. Water and various electrolyte solutions such as sodium chloride, ammonium chloride, magnesium chloride, calcium chloride, and sodium sulfate were used as a poor solvent for the lipids. When methanol and 1-propanol were used as lipid solvents, the entire phase resulted in a transparent, highly viscous gel phase. On the other hand, the profile of the coacervate precipitation of the phospholipid was observed when ethanol was used as a lipid solvent. Moreover, when 1-propanol was used as a lipid solvent, a large volume of water phase was required to induce the coacervation in the systems in comparison with methanol or ethanol. The coacervatio...

We have developed a new method to determine the marker calcein encapsulated in liposomes using ethanol or propanol instead of Triton X-100. Calcein in ethanol solution was estimated by fluorophotometry with excitation and emission wavelengths of 490 nm and 520 nm, respectively. The fluorescence intensity of calcein solubilized by ethanol was linear in the range of 10 −6−10 −4 mol/L with a correlation coefficient of 0.999. The proposed method, which was accurate and reproducible, was successfully applied to determine the amounts of ethanol-soluble drugs in liposomes.

Postoperative nausea and vomiting (PONV) with morphine therapy develops in more than 60% of patients after surgery, markedly reducing patient QOL. The prophylactic effect of several antiemetics has already been studied, but evaluations, and even those using the same drug, are not uniform. The present research involved a meta-analysis of randomized controlled trials on prophylactic drug therapy for PONV in patients receiving morphine for the treatment of postoperative pain. The efficacy of the prophylactic administration of the drugs was examined. As a result, meta-analysis of five drugs was possible and the evidence of efficacy was shown for three drugs ranked in order of an increasing odds ratio (OR) and confidence interval (CI): dexamethasone (OR: 0.23, 95% CI: 0.15-0.35, p < 0.00001), droperidol (OR: 0.27, 95% CI: 0.21-0.34, p < 0.00001), and metoclopramide (OR: 0.48, 95% CI: 0.30-0.75, p < 0.001). These results suggest that the three drugs are effective in prophylactic treatment for PONV. Of them, dexamethasone used as a prophylactic drug for PONV provided the best results. Dexamethasone was shown to reduce the incidence of PONV from 66-80% to 16-50% with a dose of 1.25 to 10 mg and to be suitable as a first drug of choice.

Novel methods and properties of liposome using various microencapsulation techniques were described. Vesicle-forming materials from biological origins, and the constitution of liposomal sensor system and functional liposomal ones capable of controlled release were also reviewed.

The properties of phospholipids as emulsifiers, stabilisers, or dispersing agents in micro- or nanoparticulate drug carriers were reviewed. Three types of purified egg yolk lecithins (PELs) with different iodine values (IV), (i.e., PEL [IV = 76], R-20 [IV = 20], and R-5 [IV = 2]) were examined to investigate differences in liposome size and the encapsulation efficiency. Encapsulation efficiencies of calcein in liposomes differed mainly depending on the solubility of each lecithin in a lipid solvent, and it was more obvious in hydrogenated lecithins. There was a significant correlation between liposome sizes and encapsulation efficiencies in nonhydrogenated PEL but not in hydrogenated R-20 and R-5. When using hydrogenated PELs as liposomal membrane materials, it was suggested that a lipid solvent should be chosen so that a lecithin completely dissolves under the preparation condition to achieve higher encapsulation efficiency. Properties of various phosphatidylcholines (PCs) used as dispersing agents and emulsifiers were examined. PCs with different lengths of acyl hydrocarbon chains and different degrees of unsaturated acyl hydrocarbon chains were selected to examine influences of a lipophilic part of PCs in emulsion and dispersion systems. For stable emulsions, it is considered beneficial for PCs to form small oil droplets and lamellae liquid crystal phase. From this perspective, saturated PCs with short hydrocarbon chains (i.e., phosphatidylcholine dilauroyl and phosphatidylcholine dimyristoyl) may have advantages in preparing stable emulsion not only by giving a smaller droplet size, but also by forming a lamellae liquid crystal phase. Compared with conventional emulsions used with PEL, emulsions prepared with PC-LM had desirable physicochemical properties in terms of the mean diameter and the stability. PC-LM will be more suitable as an emulsifier or a pharmaceutics material than lecithin used in conventional products when used for intravenous injections. The results of this study will be useful for preparation of fat emulsions and lipid emulsions in drug delivery systems.

Fluorescent probes are useful to monitor the polarity and fluidity of microenvironments. Therefore, a new amphiphilic fluorescent probe, the pyrenacylester of Rhamnolipid B, was prepared from biosurfactant (Rhamnolipid B) and pyrene. As a result of its surface activity, this probe was expected to be able to penetrate into various kinds of microdomains such as the environments of organic solvents, emulsions, dispersions, surfaces of biomembranes and polymers.

Surfactant-free emulsions by adding jojoba oil, squalane, olive oil, or glyceryl trioctanoate (medium chain fatty acid triglycerides, MCT) to electrolytic-reduction ion water containing lithium magnesium sodium silicate (GE-100) were prepared, and their physiochemical properties (thixotropy, zeta potential, and mean particle diameter) were evaluated. At an oil concentration of 10%, the zeta potential was ‒22.3 ‒ ‒26.8 mV, showing no marked differences among the emulsions of various types of oil, but the mean particle diameters in the olive oil emulsion (327 nm) and MCT emulsion (295 nm) were smaller than those in the other oil emulsions (452-471 nm). In addition, measurement of the hysteresis loop area of each type of emulsion revealed extremely high thixotropy of the emulsion containing MCT at a low concentration and the olive emulsion. Based on these results, since surfactants and antiseptic agents markedly damage sensitive skin tissue such as that with atopic dermatitis, surfactant- and antiseptic-free emulsions are expected to be new bases for drugs for external use.