• Toxicological Research
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• v.8 no.1
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• pp.17-27
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• 1992

Antigenicity of Recombinant Granulocyte macrophage colony stimulating factor(LBD-005), a newly developed drug for hematopoietic growth, was investigated in mice and guinea pigs. 1. Mice showed production of antibodies against LBD-005 (100mg/kg) with alumin]m hydroxide gel(alum) as an adjuvant, judged by the heterologous anaphylaxis(PCA) test using rats. On the other hand, antibodies against ovalbumin(OVA) inoculated with alum were definitely detected. 2. In the studies with guinea pigs, both the inoculation of LBD-005 only and of LBD-005 with complete Freund's adjuvant(CFA) as an adjuvant did not produce positive reactions in homologous passive cutaneous anaphylaxis (PCA).

• Toxicological Research
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• v.8 no.1
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• pp.29-40
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• 1992

The recombinant glycoprotein, LBD-005 (Lucky R & D Center, Biotechnology)stimulates the growth of stem cells and activates the development of the hematopoietic cell in a similar manner to the naturally occurring GM-CSF. This test was conducted to investigate if LBD-005 had any effect on fertility in male and female rats. Sprague-Dawley rats(88 of each sex) bred at KRICT, were dosed subcutaneously, at a volume of 2ml/kg body weight with LBD-005 at 0, 250, 500 or 1, 000mg/kg body weight. The male rats were dosed, from 6 weeks of asge, for 60 days prior to mating.

• Toxicological Research
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• v.9 no.1
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• pp.69-72
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• 1993

LBD-005, a newly developed recombinant granulocyte-macrophage colony stimulating factor, was tested for primary skin irritation in male New Zealand White rabbits. In the primary skin irritation test, LBD-005 was applied to intact and abraded skins for 24 hours. Primary irritation index was "0" in test and control sites of all animals' thus LBD-005 was evaluated as a non-irritatant on the basis of the criteria of Draize et al. (1994).l. (1994).

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.307-307
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• 1994

본 실험에서는 유전자 재조합으로 제조한 〔$^{125}$/I〕-labeled human GM-CSF를 사용하여 GM-CSF의 HL-60 cell의 표면에 존재하는 GM-CSF 수용체의 특성을 밝히고 수용체에 대한 binding parameter를 확인하고 Immunex(미국) 사에서 제조한 Prokine(Sargramostim)과 Sigma사에서 구입한 GM-CSF(C-9666)를 표준물질로 하여 (주) Lucky에서 제조한 GM-CSF(LBD-005)의 수용체에 대한 결합율을 측정, 각각 비교하고자 하였다. 한편 LBD-005는 glycosylation된 form과 안된 form의 혼합물이므로 당화의 정도가 수용체에 대한 결합에 미치는 영향을 알아보기 위해 glycosylated form과 혼합물(LBD-005)의 수용체에 대한 결합율을 측정 비교하였다.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.270-274
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• 1993

The acute toxicity of a recombinant granulocyte-macrophage colony stimulating factor (code name: LBD-005) was evaluated in both sexes of ICR mice, 5~6 weeks old, by the oral, subcutaneous and intravenous routes of administration. Based on the results of the acute toxicity study, LBD-005 was not considered to induce any toxic effect on the mice in mortalities, clinical findings, body weights and gross findings. It is suggested that $LD_50$ values in mice would be >48 mg/kg in the oral route and >24 mg/kg in the subcutaneous or intravenous route.

• Toxicological Research
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• v.8 no.1
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• pp.41-48
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• 1992

The actue toxicity of a recombinant granulocyte macrophage colony-stimulating factor (code name: LBD-005) was evaluated in both sexes of Sprague-Dawley rats, 4 weeks old, by the oral, subcutaneous and intravenous routes of administration. LBD-005 in the acute toxicity study in the rats was not considerde to induce any toxicological effect on the rats in mortalities, clinical findings, body weights and gross findings. It is suggested that $LD_{50}$ values in rats would be >48 mg/kg in the oral route and >12 mg/kg in the subcutaneous or intravenous route.

• Toxicological Research
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• v.9 no.1
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• pp.61-67
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• 1993

LBD-005, a newly developed recombinant granulocyte-macrophage colony-stimulating factor, was at dose levels of 0, 20, 80 and 320ng/kg/day administered subcutaneously to pregnat New Zealand White rabbits during the organogenetic period. The dams were subjected to caesarean section on day 28 of pregnancy. Effects of test substance on dams and embryonal development of fetuses were examined. No treatment-related changes in clinical signs and necropsy findings of dams were observed in all groups. At 80 and 320 ng/kg, a significant decrease in food consumption followed by a loss in body weight was found.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.188-188
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• 1994

GM-CSF는 생체내에서 백혈구의 형성을 조절하는 인자이기 때문에 골수이식을 한 환자 및 화학요법이나 방사선 치료를 받은 암환자에게서 발생하는 백혈구의 감소현상을 완화시키는 역활을 한다. 항암 보조 치료제로서 의학적 효능을 나타낼 것으로 간주되는 인체의 GM-CSF를 유전자 재조합 기술로 효모에서 발현, 정제하여 물리화학적 특성을 밝히고 역가를 측정하고자 하였다. 효모로부터 rhGM-CSF의 발현율을 상승시키기 위해 초 분비 돌연변이 균주를 선별하였고 발효 배지 조성의 차이에 따른 발현율도 비교 측정하였다. 정제된 rhGM-CSF(LBD-005)는 여러 물리화학적 특성조사를 통해 구조나 역가면에서 상대치와 거의 일치함을 보여주었다. LBD-005는 당화된 GM-CSF와 당화되지 않은 형태의 혼합물이므로 Con-A column등을 사용하여 분리하고자 하였다. 당화된 GM-CSF와 혼합물의 물리화학적 특성을 각각 조사하였으나 유사하였고 당화에 따른 역가의 차이도 없었음을 알 수 있었다.

• Toxicological Research
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• v.8 no.1
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• pp.49-61
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• 1992

Recombinant granulocyte-macrophage colony stimulating factor was subcutaneously administered to both sexes of Sprague-Dawley rats at the doses of 0, 0.5, 1 and 2mg/kg of body weight five days per week for 4 weeks to evaluate the subchronic toxicity. There were decreased 1 and 2 mg/kg. In the serum, changes were decreased alkaline phostatase(ALP) in the female groups dosed at 1 and 2mg/kg, and increased glutamic oxaloacetic transaminiase (GOT)in the male groups dosed at 0.5 and 2.0mg/kg.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.314-314
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• 1994

대상환자는 15예로, 14예에서 평가 가능하였으며 남녀비는 8:6, 중앙연령 32세(10-70세) 이었고, 대상질환은 악성골옥종 7예, 악성임파종 2예, 위암 2예, 폐암 2예, 그리고 자궁평활근육종 1예였다. rhGM-CSF 50 $\mu\textrm{g}$/$m^2$ 3예, 100 $\mu\textrm{g}$/$m^2$ 3예, 150 $\mu\textrm{g}$/$m^2$ 3예, 250 $\mu\textrm{g}$/$m^2$ 3예, 350 $\mu\textrm{g}$/$m^2$ 3예, 500 $\mu\textrm{g}$/$m^2$ 6예, 700 $\mu\textrm{g}$/$m^2$ 용량 3예에서 시행되었다. 1주기 시행한 환자는 7예, 2주기 5예, 3주기, 4주기 각각 1예씩 있다. 부작용은 50-150 $\mu\textrm{g}$/$m^2$에서 WHO grade I의 발열, 전신쇠약, 식용부진등이 관찰되었으나 grade II이상의 부작용은 없었다. 250 $\mu\textrm{g}$/$m^2$이상의 용량에서도 grade II의 발열이 관찰되었을 뿐 다른 중증의 부작용은 관찰되지 않았다. 최고용량인 700 $\mu\textrm{g}$/$m^2$ 에서도 grade II의 발열외의 중한 부작용은 관찰되지 않았다. 각 용량에 따른 백혈구 증가율(%투여제2일/투여제1일)은 130-500% 이었다. rhGM-CSF는 투여 2-4 시간후 혈중최고치 (0.42-15.4 ng/ml)가 관찰되었으며 투여 12시간까지 0.2-2 ng/ml 의 농도가 지속되었다. 소변내 rh GM-CSF 배설량은 총투여량의 1% 미만이었다.