The delayed cutaneous hypersensitivity test with picryl chloride was used to demonstrate the effect of sonicated schizophyllan (SPG-S) on cellular immunity in mice.
The increase of ear thickness in mice treated with SPG-S (0.5-10.0mg/kg) 24 hours before the sensitization with picryl chloride proved to be significantly larger than that in untreated mice on testing with picryl chloride at 7 days following sensitization.
Mice were intramuscularly injected with SPG-S (5.0g/kg) on -48, -24, 0, +24 or +48 hours of sensitization. Remarkable stimulating effect of SPG-S on the delayed hypersensitivity was recognized in all groups of mice, being somewhat lower in the group treated with SPG-S 48 hours after the sensitization.
Stimulating effects of lipopolysaccharide, concanavalin A, pokeweed mitogen and SPG-S on the delayed hypersensitivity were compared. The effect of SPG-S was similar to that of concanavalin A, a nonspecific stimulant for T cells.

View full abstract

The general pharmacological actions of KW-1062 were investigated in order to estimate the effectson the host animals.
KW-1062 showed little or no effect on the central nervous system, cardiovascular system, smooth muscle, skeletal muscle, hemolysis, blood coagulation, dermal tissue permeability and antigenicity tests at high doses.
KW-1062 showed urinative effect and ototoxicity. But ototoxicity of KW-1062 was less potent than that of gentamicin.
KW-1062 has been proved to have a safety margin wider than that of other aminoglycoside antibiotics.

View full abstract

KW-1062 is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis which was isolated from soil collected at Sagamihara by NARA, et al. The purified antibiotic showed a close similarity to gentamicin C complex in physical and chemical properties.
The antibacterial activity of KW-1062 is broad-spectrum and almost equal to that of gentamicin C complex. KW-1062 exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. and high activity against some Pseudomonas aeruginosastrain resistant to gentamicin C_1aToxicological studies of KW-1062 were carried out for safety evaluation as follows:
1. Studies were carried out to assess acute toxicity, when administered by intravenous, intramuscular, intraperitoneal, subcutaneous and oral routes to ICR strain mice and Wistar strain rats comparing with gentamicin, and by intramuscular injection to Beagle strain dogs.
2. Studies on subacute toxicity were carried out by intramuscular administration (10, 25, 63, 156, 247mg/kg) to Wistar strain rats for 30 days comparing with gentamicin (25, 63, 156mg/kg).
3. Studies on chronic toxicity were carried out by intramuscular administration (4, 10, 25, 63, 100mg/kg) to Wistar strain rats for 180 days.
The results of studies are summarized as follows:
1. Acute toxicity of KW-1062 in both mice and rats was less than that of gentamicin. Toxicity varied with species used, and it was ranked in mice>dogs>1062 247 mg/kg and gentamicin 156mg/kg respectively. Main changes observed in subacute toxicity were renal tubular disorder, normocytic anemia and bad general conditions which were due to renal tubular disorder. These changes were observed at above the dose of KW-1062 63mg/kg and gentamicin 25 mg/kg mainly.
3. The changes in chronic toxicity were almost similar to those observed in subacute toxicity, and it was observed at above the dose of KW-1062 25mg/kg mainly.
The toxicological effects observed with KW-1062 were qualitatively similar to those observed with gentamicin and other aminoglycoside antibiotics, and were quantitatively judged to be less toxic than those observed with gentamicin.

View full abstract

Toxicological studies of KW-1062 in dogs were carried out for safety evaluation as follows.
1. Studies on subacute toxicity: Beagle strain dogs were given intramuscularly KW-1062 at the dose levels of 25, 63, 100 and 156mg/kg and gentamicin (positive control) at the dose of 63 and 100mg/kg for 30 days, respectively.
2. Studies on chronic toxicity: Beagle strain dogs were intramuscularly given KW-1062 at the dose level of 4, 10, 25 and 63mg/kg for 180 days.
The results of studies are summarized as follows:
(1) In subacute toxicity, died animals were observed at the dose levels of KW-1062 100mg/kg (3/4: three out of 4 animals),156mg/kg (4/4) and gentamicin 63mg/kg (4/4), 100mg/kg (4/4) within one month.
Main changes observed in subacute toxicity studies were renal tubular disorder, which showed a close similarity to subacute toxicity studies in rats. It was observed histologically above the dose level of KW-1062 25mg/kg, but its grade was slight at the dose level of 25mg/kg. Gentamicin produced more toxic effects than KW-1062 in subacute toxicity studies in dogs. That was the same results as subacute toxicity studies in rats.
(2) The changes observed in chronic toxicity were almost similar to those observed in subacute toxicity.
Died animals were observed at the dose level of KW-1062 10mg/kg (1/6) and 63mg/kg (2/6).
Renal tubular disorder was observed above the dose level of KW-1062 10mg/kg.

View full abstract

In previous subacute toxicity studies by intramuscular administration carried out in Beagle dogs for 30 days, its maximum safety dose was not confirmed because renal tubular disorder was observed slightly at the dose of 25mg/kg.
Therefore subacute intramuscular toxicity studies were carried out again to investigate maximum safety dose using lower doses (4, 10mg/kg).
As the result of studies, the maximum safety dose was considered to be 10mg/kg because there were no abnormal changes at both doses.

View full abstract

[in Japanese]

View full abstract

Studies were performed to observe antibiotic levels in sputum of the patients with respiratory tract infections. The amoxicillin and ampicillin levels in sputum were observed for 4 or 8 hours, and the relationship between the sputum and serum levels was observed.
The results are summarized as follows:
1) In the patients received 500mg amoxicillin orally, the purulent or mucoserous sputum levels were found to be 0.05-0.6μg/ml, while the mucopurulent or mucous sputum levels were in a low range of 0.05-0.2μg/ml.
The amoxicillin levels were higher in the sputa at the 1g dose than 500mg dose with the exception of mucous sputa. In the patients received 500 mg ampicillin orally, the purulent, mucopurulent or mucoserous sputum levels were found to be 0.04 and 0.23μg/ml, while the mucous sputum levels were in a low range of 0.03-0.14μg/ml.
Both amoxicillin and ampicillin levels were comparatively high in 4-8-hour sputum.
2) In 1-2-hour sputum from the patients received 100mg amoxicillin or 250mg ampicillin by inhalation, the amoxicillin levels were found to be 7-46μg/ml, the ampicillin levels were in a range from a few tens to more than 100μg/ml, however amoxicillin and ampicillin levels were mostly null in 6-8-hours sputum.
3) The amoxicillin or ampicillin levels in the sputa, except mucous sputum, from the patients receiving dose of 500mg or 1g orally proved to be related to the serum levels. This relationship was shown to be more significant in “long actingr” cases than “high peak” cases of serum level.
4) In serum from patients receiving 100mg amoxicillin or 250mg ampicillin by inhalation, the amoxicillin levels were between 0.02-0.1μg/ml, the ampicillin levels were in a range of 0.04-0.1 μg/ml, and there was few difference in these serum levels after 1-2 hours and 4-8 hours.
These serum levels proved to be related to the sputa levels, except mucous sputum levels.

View full abstract

[in Japanese]

View full abstract