• The Korean Journal of Pharmacology
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• v.16 no.2 s.27
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• pp.55-70
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• 1980

The pharmacological and microbiological studies of Cefoperazone (T-1551, Toyama Chemical Co., Japan) were conducted in vitro and in vivo. The studies included stability and physicochemical characteristics, antimicrobial activity, animal and human pharmacokinetics, animal pharmacodynamics and safety evaluation of Cefoperazone sodium for injection. 1) Stability and physicochemical characteristics. Sodium salt of cefoperazone for injection had a general appearance of white crystalline powder which contained 0.5% water, and of which melting point was $187.2^{\circ}C$. The pH's of 10% and 25% aqueous solutions were 5.03 ana 5.16 at $25^{\circ}C$. The preparations of cefoperazone did not contain any pyrogenic substances and did not liberate histamine in cats. The drug was highly compatible with common infusion solutions including 5% Dextrose solution and no significant potency decrease was observed in 5 hours after mixing. Powdered cefoperazone sodium contained in hermetically sealed and ligt-shielded container was highly stable at $4^circ}C{\sim}37^{\circ}C$ for 12 weeks. When stored at $4^{\circ}C$ the potency was retained almost completely for up to one year. 2) Antimicrobial activity against clinical isolates. Among the 230 clinical isolates included, Salmonella typhi was the most susceptible to cefoperazone, with 100% inhibition at MIC of ${\leq}0.5{\mu}g/ml$. Cefoperazone was also highly active against Streptococcus pyogenes(group A), Kletsiella pneumoniae, Staphylococcus aureus and Shigella flexneri, with 100% inhibition at $16{\mu}g/ml$ or less. More than 80% of Escherichia coli, Enterobacter aerogenes and Salmonella paratyphi was inhibited at ${\leq}16{\mu}/ml$, while Enterobacter cloaceae, Serratia marcescens and Pseudomonas aerogenosa were somewhat less sensitive to cefoperagone, with inhibitions of 60%, 55% and 35% respectively at the same MIC. 3) Animal pharmacokinetics Serum concentration, organ distritution and excretion of cefoperazone in rats were observed after single intramuscular injections at doses of 20 mg/kg and 50 mg/kg. The extent of protein binding to human plasma protein was also measured in vitro br equilibrium dialysis method. The mean Peak serum concentrations of $7.4{\mu}g/ml$ and $16.4{\mu}/ml$ were obtained at 30 min. after administration of cefoperazone at doses of 20 mg/kg and 50 mg/kg respectively. The tissue concentrations of cefoperazone measured at 30 and 60 min. were highest in kidney. And the concentrations of the drug in kidney, liver and small intestine were much higher than in blood. Urinary and fecal excretion over 24 hours after injetcion ranged form 12.5% to 15.0% in urine and from 19.6% to 25.0% in feces, indicating that the gastrointestinal system is more important than renal system for the excretion of cefoperazone. The extent of binding to human plasma protein measured by equilibrium dialysis was $76.3%{\sim}76.9%$, which was somewhat lower than the others utilizing centrifugal ultrafiltration method. 4) Animal pharmacodynamics Central nervous system : Effects of cefoperazone on the spontaneous movement and general behavioral patterns of rats, the pentobarbital sleeping time in mice and the body temperature in rabbits were observed. Single intraperitoneal injections at doses of $500{\sim}2,000mg/kg$ in rats did not affect the spontaneous movement ana the general behavioral patterns of the animal. Doses of $125{\sim}500mg/kg$ of cefoperazone injected intraperitonealy in mice neither increased nor decreased the pentobarbital-induced sleeping time. In rabbits the normal body temperature was maintained following the single intravenous injections of $125{\sim}2,000mg/kg$ dose. Respiratory and circulatory system: Respiration rate, blood pressure, heart rate and ECG of anesthetized rabbits were monitored for 3 hours following single intravenous injections of cefoperazone at doses of $125{\sim}2,000mg/kg$. The respiration rate decreased by $3{\sim}l7%$ at all the doses of cefoperazone administered. Blood pressure did not show any changes but slight decrease from 130/113 to 125/107 by the highest dose(2,000 mg/kg) injected in this experiment. The dosages of 1,000 and 2,000 mg/kg seemed to slightly decrease the heart rate, but it was not significantly different from the normal control. All the doses of cefoperazone injected were not associated with any abnormal changes in ECG findings throughout the monitering period. Autonomic nervous system and smooth muscle: Effects of cefoperazone on the automatic movement of rabbit isolated small intestine, large intestine, stomach and uterus were observed in vitro. The autonomic movement and tonus of intestinal smooth muscle increased at dose of $40{\mu}g/ml$ in small intestine and at 0.4 mg/ml in large intestine. However, in stomach and uterine smooth muscle the autonomic movement was slightly increased by the much higher doses of 5-10 mg/ml. Blood: In vitro osmotic fragility of rabbit RBC suspension was not affected by cefoperazone of $1{\sim}10mg/ml$. Doses of 7.5 and 10 mg/ml were associated with 11.8% and 15.3% prolongation of whole blood coagulation time. Liver and kidney function: When measured at 3 hours after single intravenous injections of cefoperaonze in rabbits, the values of serum GOT, GPT, Bilirubin, TTT, BUN and creatine were not significantly different from the normal control. 5) Safety evaluation Acute toxicity: The acute toxicity of cefoperazone was studied following intraperitoneal and intravenous injections to mice(A strain, 4 week old) and rats(Sprague-Dawler, 6 week old). The LD_(50)'s of intraperitonealy injected cefoperazone were 9.7g/kg in male mice, 9.6g/kg in female mice and over 15g/kg in both male and female rats. And when administered intravenously in rats, LD_(50)'s were 5.1g/kg in male and 5.0g/kg in female. Administrations of the high doses of the drug were associated with slight inhibition of spontaneous movement and convulsion. Atdominal transudate and intestinal hyperemia were observed in animals administered intraperitonealy. In rats receiving high doses of the drug intravenously rhinorrhea and pulmonary congestion and edema were also observed. Renal proximal tubular epithelial degeneration was found in animals dosing in high concentrations of cefoperazone. Subacute toxicity: Rats(Sprague-Dawley, 6 week old) dosing 0.5, 1.0 and 2.0 g/kg/day of cefoperazone intraperitonealy were observed for one month and sacrificed at 24 hours after the last dose. In animals with a high dose, slight inhibition of spontaneous movement was observed during the experimental period. Soft stool or diarrhea appeared at first or second week of the administration in rats receiving 2.0g/kg. Daily food consumption and weekly weight gain were similar to control during the administration. Urinalysis, blood chemistry and hematology after one month administration were not different from control either. Cecal enlargement, which is an expected effect of broad spectrum antibiotic altering the normal intestinal microbial flora, was observed. Intestinal or peritoneal congestion and peritonitis were found. These findings seemed to be attributed to the local irritation following prolonged intraperitoneal injections of hypertonic and acidic cefoperazone solution. Among the histopathologic findings renal proximal tubular epithelial degeneration was characteristic in rats receiving 1 and 2g/kg/day, which were 10 and 20 times higher than the maximal clinical dose (100 mg/kg) of the drug. 6) Human pharmacokinetics Serum concentrations and urinary excretion were determined following a single intravenous injection of 1g cefoperazone in eight healthy, male volunteers. Mean serum concentrations of 89.3, 61.3, 26.6, 12.3, 2.3, and $1.8{\mu}g/ml$ occured at 1,2,4,6,8 and 12 hours after injection respectively, and the biological half-life was 108 minutes. Urinary excretion over 24 hours after injection was up to 43.5% of administered dose.

• Journal of Food Hygiene and Safety
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• v.27 no.1
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• pp.42-49
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• 2012

This study was carried out to investigate the toxicity of food Red No.2 in the Sprague-Dawley (SD) female rat for 4 weeks. SD rats were orally administered for 28 days, with dosage of 500, 1,000, 2,000 mg/kg/day. Animals treated with food Red No.2 did not cause any death and show any clinical signs. They did not show any significant changes of body weight, feed uptake and water consumption. There were not significantly different from the control group in urinalysis, hematological, serum biochemical value and histopathological examination. In conclusion, 4 weeks of the repetitive oral medication of food Red No.2 has resulted no alteration of toxicity according to the test materials in the group of female rats with injection of 2,000 mg/kg. Therefore, food Red No.2 was not indicated to have any toxic effect in the SD rats, when it was orally administered below the dosage 2,000 mg/kg/day for 4 weeks.

• Journal of the Korean Wood Science and Technology
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• v.2 no.2
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• pp.8-12
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• 1974

1. If one unity is given to the prongs whose ends touch each other for estimating the internal stresses occuring in it, the internal stresses which are developed in the open prongs can be evaluated by the ratio to the unity. In accordance with the above statement, an equation was derived as follows. For employing this equation, the prongs should be made as shown in Fig. I, and be measured A and B' as indicated in Fig. l. A more precise value will result as the angle (J becomes smaller. $CH=\frac{(A-B') (4W+A) (4W-A)}{2A[(2W+(A-B')][2W-(A-B')]}{\times}100%$ where A is thickness of the prong, B' is the distance between the two prongs shown in Fig. 1 and CH is the value of internal stress expressed by percentage. It precision is not required, the equation can be simplified as follows. $CH=\frac{A-B'}{A}{\times}200%$ 2. Under scheduled drying condition III the kiln, when the weight of a sample board is constant, the moisture content of the shell of a sample board in the case of a normal casehardening is lower than that of the equilibrium moisture content which is indicated by the Forest Products Laboratory, U. S. Department of Agriculture. This result is usually true, especially in a thin sample board. A thick unseasoned or reverse casehardened sample does not follow in the above statement. 3. The results in the comparison of drying rate with five different kinds of wood given in Table 1 show that the these drying rates, i.e., the quantity of water evaporated from the surface area of I centimeter square per hour, are graded by the order of their magnitude as follows. (1) Ginkgo biloba Linne (2) Diospyros Kaki Thumberg. (3) Pinus densiflora Sieb. et Zucc. (4) Larix kaempheri Sargent (5) Castanea crenata Sieb. et Zucc. It is shown, for example, that at the moisture content of 20 percent the highest value revealed by the Ginkgo biloba is in the order of 3.8 times as great as that for Castanea crenata Sieb. & Zucc. which has the lowest value. Especially below the moisture content of 26 percent, the drying rate, i.e., the function of moisture content in percentage, is represented by the linear equation. All of these linear equations are highly significant in testing the confficient of X i. e., moisture content in percentage. In the Table 2, the symbols are expressed as follows; Y is the quantity of water evaporated from the surface area of 1 centimeter square per hour, and X is the moisture content of the percentage. The drying rate is plotted against the moisture content of the percentage as in Fig. 2. 4. One hundred times the ratio(P%) of the number of samples occuring in the CH 4 class (from 76 to 100% of CH ratio) within the total number of saplmes tested to those of the total which underlie the given SR ratio is measured in Table 3. (The 9% indicated above is assumed as the danger probability in percentage). In summarizing above results, the conclusion is in Table 4. NOTE: In Table 4, the column numbers such as 1. 2 and 3 imply as follows, respectively. 1) The minimum SR ratio which does not reveal the CH 4, class is indicated as in the column 1. 2) The extent of SR ratio which is confined in the safety allowance of 30 percent is shown in the column 2. 3) The lowest limitation of SR ratio which gives the most danger probability of 100 percent is shown in column 3. In analyzing above results, it is clear that chestnut and larch easly form internal stress in comparison with persimmon and pine. However, in considering the fact that the revers, casehardening occured in fir and ginkgo, under the same drying condition with the others, it is deduced that fir and ginkgo form normal casehardening with difficulty in comparison with the other species tested. 5. All kinds of drying defects except casehardening are developed when the internal stresses are in excess of the ultimate strength of material in the case of long-lime loading. Under the drying condition at temperature of $170^{\circ}F$ and the lower humidity. the drying defects are not so severe. However, under the same conditions at $200^{\circ}F$, the lower humidity and not end coated, all sample boards develop severe drying defects. Especially the chestnut was very prone to form the drying defects such as casehardening and splitting.

• The Korean Journal of Air & Space Law and Policy
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• v.32 no.1
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• pp.225-285
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• 2017

In regard to the regulations related to the RPA(Remotely Piloted Aircraft), which is sometimes called in other countries as UA(Unmanned Aircraft), ICAO stipulates the regulations in the 'RPAS manual (2015)' in detail based on the 'Chicago Convention' in 1944, and enacts provisions for the Rules of UAS or RPAS. Other contries stipulates them such as the Federal Airline Rules (14 CFR), Public Law (112-95) in the United States, the Air Transport Act, Air Transport Order, Air Transport Authorization Order (through revision in "Regulations to operating Rules on unmanned aerial System") based on EASA Regulation (EC) No.216/2008 in the case of unmanned aircaft under 150kg in Germany, and Civil Aviation Act (CAA 1998), Civil Aviation Act 101 (CASR Part 101) in Australia. Commonly, these laws exclude the model aircraft for leisure purpose and require pilots on the ground, not onboard aricraft, capable of controlling RPA. The laws also require that all managements necessary to operate RPA and pilots safely and efficiently under the structure of the unmanned aircraft system within the scope of the regulations. Each country classifies the RPA as an aircraft less than 25kg. Australia and Germany further break down the RPA at a lower weight. ICAO stipulates all general aviation operations, including commercial operation, in accordance with Annex 6 of the Chicago Convention, and it also applies to RPAs operations. However, passenger transportation using RPAs is excluded. If the operational scope of the RPAs includes the airspace of another country, the special permission of the relevant country shall be required 7 days before the flight date with detail flight plan submitted. In accordance with Federal Aviation Regulation 107 in the United States, a small non-leisure RPA may be operated within line-of-sight of a responsible navigator or observer during the day in the speed range up to 161 km/hr (87 knots) and to the height up to 122 m (400 ft) from surface or water. RPA must yield flight path to other aircraft, and is prohibited to load dangerous materials or to operate more than two RPAs at the same time. In Germany, the regulations on UAS except for leisure and sports provide duty to avoidance of airborne collisions and other provisions related to ground safety and individual privacy. Although commercial UAS of 5 kg or less can be freely operated without approval by relaxing the existing regulatory requirements, all the UAS regardless of the weight must be operated below an altitude of 100 meters with continuous monitoring and pilot control. Australia was the first country to regulate unmanned aircraft in 2001, and its regulations have impacts on the unmanned aircraft laws of ICAO, FAA, and EASA. In order to improve the utiliity of unmanned aircraft which is considered to be low risk, the regulation conditions were relaxed through the revision in 2016 by adding the concept "Excluded RPA". In the case of excluded RPA, it can be operated without special permission even for commercial purpose. Furthermore, disscussions on a new standard manual is being conducted for further flexibility of the current regulations.