• Biomolecules & Therapeutics
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• 제5권3호
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• pp.316-322
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• 1997

CJ-50001 is a recombinant granulocyte-colony stimulating factor (rG-CSF) synthesized by recombi-nant DNA technology using E. coli as an expression system. The general pharmacological properties of CJ-50001 were evaluated in mice, rats, dogs and isolated guinea pig ileum. The doses are 100, 300 and 1, 0007g/kg, i.v. for mice and rats, 1, 10 and 100$\mu$g/kg, 1.v. for dogs and 1 and 10$\mu$g/ml for isolated guinea pig ileum. Intravenous administration of CJ-50001 at this dose range did not affect general behavior, central nervous system, smooth muscles, gastrointestinal system, cardiovascular and respiratory system and water and electro-lytes excretion. In summary, CJ-50001 had no harmful pharmacological erect in these studies even up to the 200-fold expected clinical dose, 2507g/man.

• Biomolecules & Therapeutics
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• 제6권4호
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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%.

• Toxicological Research
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• 제13권3호
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• pp.303-306
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• 1997

Antigenic potential of genetically engineered human granulocyte colony-stimulating factor (CJ-50001) was assessed in guinea pigs and mice. In active systemic anaphylaxis (ASA) test, although CJ-50001 at 50 $\mu\textrm{g}$ /head induced anaphylactic responses, CJ-50001 5 $\mu\textrm{g}$ /head alone or 50 $\mu\textrm{g}$ / head with adjuvant did not induce anaphylactic responses. In passive systemic anaphylaxis test (PCA) or passive hemagglutination test (PHA), CJ-50001 did not induce positive responses. It is concluded that, in light of the fact that CJ-50001 was antigenic only in ASA but not in PCA or PHA and also that CJ-50001 is a foreign human recombinant protein to guinea pigs, CJ-50001 may not induce systemic allergic react-ion in its clinical use in human.

• Biomolecules & Therapeutics
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• 제6권1호
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• pp.89-94
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• 1998

CJ50001 is a recombinant human granulocyte colony-stimulating facto, (rHuG-CSF) that stimulates the formation of neutrophils from bone marrow stem cells. It was produced in E. colt and purified through refolding and several processes. We produced CS970125(300) using purified C150001 and additives in order to test the stability of CJ50001. When CS970125(300) was stored at 50'S for more than 1 week, high molecular weight proteins were formed and those proteins were detected by non-reducing SDS-PAGE, gel filtration HPLC, and Western blot. Those proteins showed single band at the same position of CJ50001 in reducing SDS-PAGE. These data indicated that those high molecular weight proteins were the multimers of C150001. In biological assays, iu viro and in viro, the multimers did not have biological activity and inhibitory action to that of CJ 50001. The mutimers did not induce toxicity in mice and rats in acute toxicity test. These results suggest that if Cs970125(300) containing CJ50001 is stored at 5$0^{\circ}C$, CJ50001 will be the multimers that do not have biological activity and inhibitory effect to CJ50001 and do not induce acute toxicity.

• Toxicological Research
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• 제13권3호
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• pp.293-296
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• 1997

The acute toxicity study of CJ-50001, a recombinant granulocyte-colony stimulating factor (rG-CSF), was performed in Sprague Dawley (SD) rats and beagle dogs. CJ-50001 was administered up to maximum dose 5,000 $\mu\textrm{g}$/kg (i.v.) and 10,000 $\mu\textrm{g}$/kg (p.o.) in SD rats and 5,000 $\mu\textrm{g}$/kg (i.v.) in beagle dogs. In these experiments, there were no death and harmful clinical changes which were related to CJ-50001. In conclusion, $LD_{50}$ of CJ-50001 is over 5,000 $\mu\textrm{g}$/kg, i.v. in SD rats and beagle dogs, and over 10,000 $\mu\textrm{g}$/kg, p.o. in SD rats.

• Toxicological Research
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• 제13권3호
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• pp.307-310
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• 1997

The local irritation study (skin & occular irritation tests) of CJ-50001, a rG-CSF (recombinant granulocyte-colony stimulating factor) was performed in Japanese White rabbits. CJ-50001 was administered at a dose of 150 $\mu\textrm{g}$/rabbit (300$\mu\textrm{g}$ /ml, 0.5 ml) to the bare skin and at a dose of 30 $\mu\textrm{g}$/rabbit (300 $\mu\textrm{g}$/ml, 0.1 ml) to the conjunctival sac of the eye, respectively. In these experiments, there were no clinical signs which were related to CJ-50001 compared with control group. In conclusion, CJ-50001 doesn't have any irritating activity to skin and eye as 0.03% solution.

• Biomolecules & Therapeutics
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• 제5권4호
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• pp.380-383
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• 1997

CJ-50001 is a recombinant granulocyte-colony stimulating factor (rG-CSF) developed by Cheil Jedang R&D Center. The effects of CJ-50001 on the increase of peripheral neutrophil count following intravenous and subcutaneous single administration at a dose of 20$\mu$g/kg in normal ICR mice and SD rats, respectively, were compared with those of Grasin, a control drug. Both CJ-50001 and Grasin significantly increased the peripheral neutrophil number in four treatment groups and the maximum number of neutrophil was achieved at 12 to 18 h in rats and mice, respectively. The dose dependency test was studied for CJ-50001 only in normal mice by intravenous or subcutaneous administration. When administered i.v or s.c at the various doses in normal mice, CJ-50001 significantly increased the neutrophil number over the dose of 160 ng/kg, compared with the vehicle control group. From these results, it was concluded that CJ-50001 showed efficacy similar to Grasin in the peripheral neutrophil count increase.

• Biomolecules & Therapeutics
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• 제5권4호
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• pp.376-379
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• 1997

The peripheral neutrophil recovery test was conducted to determine the efficacy of CJ-50001, a drug developed in Cheil Jedang R&D center as a recombinant granulocyte-colony stimulating factor (rG-CSF). Grasin was used as control drug. CJ-50001 and Gratin were subcutaneously administered to ${\gamma}$-ray irradiated mice for 21 days at a dose of 10$\mu$g/kg after bone marrow transplantation and the recovery of neutrophil number was examined on the days of 9, 13, 17, and 21 after the drug administration. It was observed that the peripheral neutrophil number of the vehicle control group was recovered to the normal level on the day of 13 after the transplantation whereas the group administered with CJ-50001 and Grasin respectively, showed the normal level of peripheral neutrophil number on 9th day after the bone marrow transplantation. The number of peripheral neutrophils reached the highest level on the 21 st day of drug administration, and was recovered to the normal level on the 4th day after ceasing of the drug administration (on the 25th day of the transplantation). Thus, it was presumed that CJ-50001 showed efficacy similar to Grasin on the peripheral neutrophil recovery after bone marrow transplantation.

• 수산해양교육연구
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• 제27권5호
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• pp.1470-1478
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• 2015

Adjuvant is an immune enhancer commonly used during vaccination to enhance the host immune response. In the present study, we produced the several recombinant protein from immune related gene of olive flounder (Paralichthys olivaceus). Especially, to produce the soluble type of recombinant protein, we constructed the MBP (Maltose binding protein) fusion G-CSF (Granulocyte colony stimulating factor) recombinant protein among the flounder immune related genes. To verify the immune stimulatory effect and safety of this recombinant protein (rPoGCSF), expression changes of several immune genes were tested using quantitative real-time PCR method with gene specific primer from flounder head kidney leukocytes. As a result, we confirmed that the rPoGCSF has an ability of immune stimulatory effect, also it has broad range of pH and temperature.

• Toxicological Research
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• 제31권4호
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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.