• YAKHAK HOEJI
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• v.35 no.2
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• pp.135-141
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• 1991

The general pharmacological tests with rhGM-CSF indicated that it had no influences on rotarod and locomotor activity tests, but shortened hexobarbital-sleeping time at the large dose of 3 mg/kg s.c. in mice. It elicited no hypothermic, analgesic and antiepileptic action. No influences on blood pressure and respiration in rabbits were observed at the dose of 1 mg/kg, i.v. and it did neither affect the receptors of adrenaline, acetylcholine, serotonin, histamine, kinin and oxytocin, nor antagonize the actions of histamine, serotonin and oxytocin at its concentrations of 1$\times$$10^{-6}$g/ml. However, this substance was demonstrated to stimulate the formation of leucocytes in rats.

• Bulletin of the Korean Chemical Society
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• v.35 no.12
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• pp.3489-3494
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• 2014

In search of new antileukopenia agents, twenty dithiolopyrrolone derivatives were synthesized and evaluated for their leukocyte-increasing activities in normal mice. Among the synthesized compounds 4-23, compounds 5 and 6 showed significant leukocyte-increasing activity ( p < 0.01), and compounds 4, 9 and 16 had a moderate effect ( p < 0.05). Compound 5 also displayed stronger leukocyte-increasing activity than that of the positive recombinant human granulocyte colony stimulating factor (rhG-CSF). Above all, compound 5 would be a potential antileukopenia agent which deserved further research.

• Biomolecules & Therapeutics
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• v.2 no.3
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• pp.270-280
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• 1994

This study was conducted to evaluate the repeated dose toxicity of DA-3030, a recombinant human granulocyte colony stimulating factor(rhG-CSF), in rats. DA-3030 was administered intravenously once a day for 4 weeks to 20 males and 20 females per group at doses of 0(control), 115 and 1150 $\mu\textrm{g}$/kg, and to 15 males and 15 females per group at doses of 1.15 and 11.5$\mu\textrm{g}$/kg. After the administration period, 5 males and 5 females per group in the 0,115 and 1150 $\mu\textrm{g}$/kg groups were placed on withdrawal for 2 weeks. Through-out the study, all the rats survived. The administration of DA-3030 induced, a marked increase in the number of peripheral neutrophils, elevation of serum alkaline phosphatase activity, and splenomegaly in the rats of both sexes receiving 115 or 1150 $\mu\textrm{g}$/kg. Histopathologic examination revealed extramedullary granulopoiesis in spleen and liver, and increase in the number of activated macrophages in spleen in rats of both sexes in 115 and 115 $\mu\textrm{g}$/kg groups, and increased M/E ratio in 11.5, 115 and 1150$\mu\textrm{g}$/kg groups. Most of the changes produced by DA-3030 were thought to be attributable to exaggerated pharmacological effect of the drug, and subsided or disappeared after the recovery period. Under the present condition, no effect dose of DA-3030 is estimated at 1.15 $\mu\textrm{g}$/kg/day.

• Korean Journal of Food Science and Technology
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• v.37 no.1
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• pp.67-72
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• 2005

Antioxidative activity of crude saponin fraction (CSF) prepared from Basidiomycota cultured with fresh ginseng (Panax ginseng C.A. Meyer) as substrate was investigated by analyzing CSFs for ginsenoside and phenolic compounds. On TLC chromatogram, ginsenosides such as $Rg_{2},\;Rg_{3}$, and $Rh_{1}$ which were rare in fresh ginseng, were identified. CSF of Phellinus linteus culture product showed the highest total phenolic content and electron donating ability (EDA), suggesting phenolic compounds contribute to EDA. In vitro lipid peroxidation was inhibited most by CSF of Ganoderma lucidum, indicating that the highest EDA does not imply highest inhibition against lipid peroxidation. Tyrosinase was also inhibited mostly by CSF of G. lucidum. These results suggest culture of Basidiomycota with fresh ginseng has more active substances than fresh ginseng alone.

• Toxicological Research
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• v.31 no.4
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• pp.371-392
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• 2015

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of $1000{\mu}g/kg/day$. Rats received TS-DP2 intravenously at doses of 250, 500, and $1000{\mu}g/kg/day$ once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 $500{\mu}g/kg/day$ and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was $250{\mu}g/kg/day$, and no observed adverse effect level (NOAEL) in females was $250{\mu}g/kg/day$ in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures ($AUC_{0-24h}$ and $C_0$) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

• 대한임상약리학회:학술대회논문집
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• 1998.12a
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• pp.72-72
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• 1998

• Biomolecules & Therapeutics
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• v.6 no.4
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• pp.400-405
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• 1998

The pharmacokinetics of CJ-50001 (recombinant human granulocyte-colony stimulating factor, developed by R&D center of Cheil Jedang Corp.) were investigated in rats and dogs. The serum concentrations of CJ-50001 were measured by a sandwich enzyme immunoassay. After single intravenous (iv) administration of Cf-50001 to rats at a dose of 5 $\mu$g/kg, the mean terminal half-life and area under the concentration-time curve (AUC) were 0.96 h and 124.497g . h/ml, respectively. After single subcutaneous (sc) administration at the same dose, maximum serum concentration was observed at about 2 hours after administration, and the mean terminal half-life, AUC and the bioavailability were 1.11 h,63.58$\mu$g . h/ml and 51.07%, respectively. In repeated dosing studies, CJ-50001 was administered iv and sc to rats at a daily dose of 5$\mu$g/kg for 7 days. The pharmacokinetic parameters, such as mean AUC and terminal half-life, were no significantly different from those of single administration. Following single iv and sc administration of CJ-50001 to dogs at a dose of 5 $\mu$g/kg, mean AUCs were much higher than those of rats, due to the decreased clearence (CL). After sc administration to dogs, maximum serum concentration was observed at 2~4 hours after administration and the bioavailability was 54.60%.

• Biomolecules & Therapeutics
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• v.10 no.4
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• pp.268-273
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• 2002

Mutagenic potential of HM10411 (recombinant human granulocyte colony stimulating factor) was evaluated by bacterial reverse mutation test, in vitro chromosome aberration test and in vivo micronucleus test. The bacterial reverse mutation test was performed using the histidine auxotroph strains of Salmonella typhimurium TA100, TA1535, TA98, TA1537 and tryptophan auxotroph strain of Escherichia coli WP2 uvrA. The negative results of the bacterial reverse mutation test suggest that HM10411 does not induce mutation, in the genome of Salmonella typhimurium and E. coli under the conditions used. In addition, it has little clastogenicity either in vitro chromosome aberration test or in vivo micronucleus test. For in vitro chromosomal aberration test, Chinese hamster lung(CHL) cells were exposed to HM10411 of 23, 46 or 92 $\mu\textrm{g}$/ml for 6 or 24 hours in the absence and for 6 hours in the presence of metabolic activation system. There was no significant increase in the number of aberrant metaphase in HM 10411-treated groups at any dose levels both in the presence and absence of metabolic activation system. The micronucleus test was carried out using specific pathogen free(SPF) 7-week old male ICR mice, The test item, HM10411 was intraperitoneally administered at 1150, 2300 or 4600 $\mu\textrm{g}$/kg once a day for 2 consecutive days. There was no significant increase in the frequencies of micronucleated polychromatic erythrocytes(PCEs) at any treated groups compared with negative control group. Therefore, these results demonstrate that the test item, HM10411, was not mutagenic under the condition of these studies.