In the case of severely injured or weak patients, one of the most difficult problems to physicians is the management of pressure sores. It is generally known, however, that severely injured deep pressure sores extended to the bones are cured only by surgical treatment.
On the other hand, it has been reported that sugar promotes granulation of tissues and thus cures wounds. We examined the effect of sugar mixed with povidone-iodine or silver-sulfadiazine ointment on the deep pressure sores of Grade 3/4 (Shea 1975). Within the first week of sugar therapy, the color of the ulcers turned to fresh pink, thus indicating that the circulation of the sore and its surrounding were improved. Then the ulcers gradually disappeared and filled with pink granulation tissue. However, long-term application of povidone-iodine sugar sometimes caused infection with Pseudomonas aeruginosa, resulting in retardation of healing. Use of silver-sulfadiazine sugar cured the infection and promoted granulation of tissues. Finally the ulcers were covered with skin. But duration of the therapy depended upon the degree of the sores as well as of the conditions of patients. Thus, it seems that sugar therapy is a useful means for the treatment of severe pressure sores.

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The in vitro dissolution rate of 3 commercial phenytoin (PHT) products with different particle sizes (PHT A-1, A-2 from manufacturer A, and PHT B from manufacturer B) was examined by USP rotating basket method. The difference of the dissolution rate was due to the difference in particle sizes. Particularly in the 1st fluid, 2nd fluid and borate buffer with 0.1% Polysorbate 80, the dissolution rate was significantly enhanced in the order of PHT A-l<PHT A-2< PHT B. The quantity of Polysorbate 80 was related to the dissolution rate of PHT B, but not of PHT A-1 and PHT A-2. These findings should have resulted from the difference in the pharmaceutical factors.

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Compatibility tests of 1.5% lysozyme chloride dry syrup with 46 other drugs in solution were made. 3 g of a lysozyme preparation was mixed with 1/2 to 1/3 of daily dose of each drug, diluted with water to 30 ml and examined over 28 days at 4 different temperatures (5±1°C, 15±2°C, 25±2°C, 30±1°C) for changes in appearance, odor, redispersion and lysozyme activity. Both the Atarax-P syrup and Bisolvon syrup solutions immediately yielded nondispersive precipitates. The Inolin syrup mixture decreased to 75% in residual activity after 3 days a, t 15°C. Therefore, we concluded that the above-mentioned combinations are not feasible, and that attention must be paid when mixng this preparation with 7 other drugs.
Most of the combinations could be preserved for 28 days at 5°C. However, in the case of suspension mixtures, the lysozyme chloride may be absorbed and cause coprecipitation, thus making it necessary to take the mixture immediately after thorough shaking.

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Compatibility tests of 1.5% lysozyme chloride dry syrup with 59 other drugs were made. 3g of a powdered lysozyme preparation was mixed with 1/2 to 1/3 of daily dose of each drug, and wrapped in polyethylene glassine or polyethylene sheets. Each test was continued over 28 days under 3 different conditions (5±1°C, RH 45-50%; 25±2°C, RH 70-75%; 30±1°C, RH 90-92%) to check changes in apPearance and lysozyme activity.
Very little change was, observed in the tests made under the 25±2°C condition, but the possibility remains that the lysozyme activity may decrease when mixed with Vibramycin dry syrup, Panacid dry syrup or Baktar Granules. Although there may be no change in appearance, care must be exercised when the lysozyme preparation is compounded with aspirin, sulpyrine and alkaline agents, because the compounds may lose their lysozyme activity.

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Compatibility tests of 20 lysozyme chloride fine granules with 64 other drugs were made. The mixtures wrapped in polyethylene glassine or polyethylene sheets were examined over 28 days under 3 different conditions (5±1°C, RH 45-50%; 25±2°C, RH 70-75%; 30±1°C, RH 90-92%) to check the changes in appearance and lysozyme activity. Under the 25±2°C condition, only Resmit fine granules have proved incompatible because the mixture resulted in a color change on the 7th day of the test. This change in color resulted from the action of Resmit fine granules on lysozyme chloride fine granules, but this phenomenon did not occur under the 5±1°C condition. We also concluded that attention must be paid when mixing this 20% lysozyme chloride fine granules with Combipenix granules, Panacid dry syrup, and Baktar granules.
However, 20% lysozyme chloride fine granules, when wrapped in polyethylene, can be mixed with 35 other drugs (about 55%) even in the 30±1°C condition. Mixtures with other drugs cannot be preserved for a long period of time, primarily due to changes in appearance caused by moisture. Thus we have concluded that lysozyme chloride fine granules are a stable preparation and can be mixed with the majority of other drugs if exposure to moisture is avoided.

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In order to prevent cross-contamination caused by the mixing apparatus for dispensing powders, we proposed use of polyethylene bag which is disposable at each occasion of dispensing and is usable as a mixing apparatus. The degree of mixing of this bag was investigated using lactose powder and eosin-colored lactose powder, and efficiency of the bag was compared with that of an automatic dispensing mixer. As an index of the degree of mixing, coefficients of variation (C. V.) obtained from the concentrations of eosin were used. C. V. values not more than 6.08 was judged to be “good mixing.” As a result, good mixing in the disposable bag with total contents of 20 to 80 g was obtained by more than 40-time shaking. Mixing ratio of the 2 kinds of powder did not affect the degree of mixing. No differences were found between the disposable bag and automatic dispensing mixer. The above results indicated that the mixing procedure using the polyethylene bag is practically useful for powder dispensing.

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The L-DOPA levels in plasma were determined by high performance liquid chromatography. Separation of L-DOPA from plasma was achieved by alumina adsorption using tris-HCI buffer (pH 8.6) without deproteinization. Adsorption of L-DOPA onto alumina showed liquid-solid equilibriums with constant rates at both adsorption and extraction steps. For this reason, the recovery of L-DOPA from plasma varied with alumina amounts, acidity and volume of the eluate used. Maximal recovery (89%) was achieved when 50 mg of alumina and 1ml of eluate of 1 M AcOH were used. Norepinephrine and epinephrine, as well as L-DOPA, were assayed by this method, and linear caribration curves were obtained as little as 2000pg/ ml for norepinephrine and epinephrine, and 5μg/ ml for L-DOPA. Reproducibility was demonstrated by a day-to-day coefficient of variation based on the change of assay value for standard plasma sample containing 1μg/ ml of L-DOPA. The day-to-day coefficient of variation was less than 4%, and the within-run coefficient of variation was less than 3%.
The interference by other probable. catechols in plasmt such as dopamine and carbidopa which is often administered with L-DOPA were not found. The method involving alumina extraction established in this study has general applicability in very accurately determining L-DOPA, norepinephrine and epinephrine in plasma.

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In order to obtain information on the stability of Lacretin dry syrup (long-acting antihistamine preparation), we studied its compatibility with drugs in common use. Two presentations of the mixtures were investigated: powder and liquid preparations. 34 kinds of powder preparations were selected for the compatibility study, and change in appearance was examined bysensory evaluation method. Under severe conditions (30°C, RH 92%), these samples began to change in appearance 5 days after the start of the test, and 30 samples showed an apparent change after 14 days. Under moderate conditions (20°C, RH 75%), only 3 samples produced a change in appearance. Under favorable conditions (5°C, RH 52%), no changes were observed.
30 kinds of liquid preparations were investigated for change in appearance and pH. Further, 9 samples in the state of suspension at the time of preparation were tested for redispersion. Formerly, in accordance with the test method based on the criterion on compatibility of internal liquid medicines proposed by the JPA Preparation Technique Committee, we had a trouble to manipulate test tubes at 5-second intervals. In the present experiment, we used a new automatic instrument with good reproducibility. In the redispersion test, 4 samples were found to be incompatible.

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High performance liquid chromatography (HPLC) was used in determination of betamethasone-17-valerate (BM-V) incommercial ointment. The conditions of HPLC were as follows-model: Shimadzu LC-4A; detector: SPD-2SA; wavelength: 239nm; column: Zorbax ODS (4.6×250mm); short guard-column: Zorbax ODS (4.0×50mm); mobile phase: MeOH: H₂O= 75: 25 (v/v); flow rate: 1ml/ min; pressure: 100kg/cm² (at 40°C). BM-V in commercial ointment and other ointment or cream admixture was also measured by the present HPLC method. BM-V ointment or admixture was dissolved or suspended into cyclohexane, and then MeOH: H₂O (9: 1 or 8: 2) was used to extract BM-V from cyclohexane. Naphthalene was used as an internal standard material. 10μl of extract solution was directly injected into HPLC column. The amount of BM-V was determined by comparing the peak height of BM-V to that of naphthalene on the chromatogram.
The results showed the possibility that compatibility of BM-V ointment admixed with other ointment or cream can be studied with the present method.

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In an attempt to improve the anticonvulsant therapy, the serum concentration of phenobarbital (PB), valproic acid (VPA) and phenytoin (PHT) was assessed in 62 pediatric patients who were treated with these drugs administered alone or concomitantly. The serum concentration of PB was higher when administered concomitantly with PHT or VPA as compared with that when administered alone. Conversely, the serum concentration of VPA tended to be lowered when administered in conjunction with PB. Good correlations were demonstrated between the determined concentration of PB or VPA and those predicted by the pharmacokinetic calculation.
A case report was described referring to the therapeutic schedule of PB and PHT, their serum concentrations, occurrence of adverse effects and the symptoms. It was indicated that determination of serum concentration of administered anticonvulsants may prevent the possible adverse effects and be useful for improving the therapeutic schedule.

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Seven species of bacteria, viz. Leucosporidium spp., Micrococcus luteus, Staphylococcus epidermidis, Staphylococcus aureus, Planococcus citreus, Micrococcus varians and Bacillus cereus, were incubated with resuspended red blood cells, and were examined for their growth at 4°, 157deg;, 25° and 37°. No bacterial growth was observed in the resuspended red blood cells at the temperatures up to 15°, but S. aureus and B. cereus showed a rapid growth at 25° and 37°C. Thus, in ordor to minimize bacterial contamination, it is important to reduce the incubation time as much as possible when blood cell preparations are incubated at 37°C for transfusion.

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Polyethylene bottles are used as containers for syrup or liquid medicines. Easiness of pouring syrup out of a bottle or measurement of syrup depends on viscosity of the syrup on the container surface and on wetting between the syrup and the container surface. We studied the rheological property of some syrups by measuring their viscosity with rheometer and by plotting the quantitative changes in abhesion. The results were as follows:
1) Adhesion of syrups on the surface of polyethylene containers was less than that on glass containers. 2) Most commercial syrup products showed the property of non-Newtonian fluid, and the refractions in the plot Wt^-2 against t were observed. 3) There was little difference of adhesion among several commercial syrup products in polyethylene containers.

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