• Title/Summary/Keyword: rhG-CSF

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Therapeutic Effect of Different Doses of Recombinant Human Granulocyte Colony-Stimulating Factor(rhG-CSF) on Neonatal Sepsis Complicated by Neutropenia (호중구 감소증이 합병된 신생아 패혈증에서 Recombinant Human Granulocyte Colony-Stimulating Factor(rhG-CSF)의 투여 용량에 따른 치료 효과)

  • Choi, Moon Young;Jung, Yeon Sook;Son, Dong Woo;Ahn, Hyo Seop
    • Clinical and Experimental Pediatrics
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    • v.45 no.4
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    • pp.439-448
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    • 2002
  • Purpose : The aim of this study is to determine and compare the effects of adjunctive therapy with different doses of recombinant human granulocyte-colony stimulating factor(rhG-CSF) on reversing sepsis-associated neonatal neutropenia, and their survival rate in a group I/II-type trial. Methods : RhG-CSF was injected subcutaneously to 10 septic-neutropenic neonates with doses of $10{\mu}g/kg$ from Oct. 1995 to Sep. 1996, and was administered to another 12 septic-neutropenic neonates with doses of $5{\mu}g/kg$ from Oct. 1996 to Sep. 1997. Neutrophilic responses and the outcomes of both groups were compared. Results : In the rhG-CSF $10{\mu}g/kg$ treated group and in the $5{\mu}g/kg$ treated group, the absolute neutrophil count(ANC) was $1,065{\pm}89$($mean{\pm}SEM$) and $1,053{\pm}131$, respectively. The only difference between the two groups was the peak ANC at 48 hours. Eight patients from the remaining nine of rhG-CSF $10{\mu}g/kg$ treated group(88.9%) and ten in $5{\mu}g/kg$ treated group(83.3%) survived the sepsis and were discharged without any problems. Conclusions : RhG-CSF can increase the neutrophil count in critically ill septic neutropenic neonats. The survival rate of both groups were up to 90%. This finding suggests that both doses of rhG-CSF may be effective in a therapeutically useful time frame to treat septic neonates with neonatal neutropenia attributable to bone marrow supression or neutrophil consumption.

Pharmacokinetics of Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) Following Intravenous, Intramuscular and Subcutaneous Administration of HM10411 and Filgrastim to Rats and Mice (인과립구 콜로니 자극인자 제제인 HM10411와 필그라스팀의 정맥, 근육 및 피하 주사시 흰쥐와 마우스에서의 약물 동태)

  • Kim, In-Wha;Lee, Sang-Hoon;Kim, Young-Min;Jung, Sung-Youb;Kwon, Se-Chang;Lee, Gwan-Sun;Chung, Suk-Jae;Shim, Chang-Koo
    • Journal of Pharmaceutical Investigation
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    • v.31 no.2
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    • pp.89-94
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    • 2001
  • The pharmacokinetics of recombinant human granulocyte colony stimulating factor (rhG-CSF) following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration of HM1041l-lyo and HM10411-liq (lyophilized and liquid formulations of rhG-CSF, recently under development by Hanmi Pharmaceutical Company) were studied in rats, and compared with that of Filgrastim (conventional formulation of rhG-CSF on market). The plasma concentration of rhG-CSF was quantified using a specific ELISA. The pharmacokinetic parameters of rhG-CSF, after i.v., i.m. and s.c. administration of Filgrastim, HM1041l-lyo and HM1041l-liq to rats at a rhG-CSF dose of $10\;{\mu}g/kg$, were almost identical among the three formulations. No dose-dependency was observed in the pharmacokinetic parameters of rhG-CSF following i.v. administration in the dose range of $5{\sim}100\;{\mu}g/kg$. rhG-CSF, after i.v. administration of the three preparations at a dose of $10\;{\mu}g/kg$ to rats, was detected at low levels in all of the body tissues with highest tissue/plasma ratio of $0.46{\sim}0.51$ for the kidney at 30 min after the administration. The pharmacokinetics of rhG-CSF, after i.v. administration to mice at a dose of $10\;{\mu}g/kg$, were comparable among the three formulations. In conclusion, HM10411-lyo and HM10411-liq exhibited similar pharmacokinetics for rhG-CSF with Filgrastim regandless of animal species. Considering the fact that HM10411 series, contrary to Filgrastim, are proteins lacking a methionine residue, the methionine moiety in rhG-CSF molecule does not appear to influence the pharmacokinetics of the protein significantly.

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Long-acting Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) with a Trimer-Structured Polyethylene Glycol

  • Jo, Yeong-Woo;Lee, Mee-Yong;Choi, Yun-Kyu;Lee, Sung-Hee;Kang, Soo-Hyoung;Na, Kun;Youn, Yu-Seok;Choi, Eung-Chil
    • Journal of Pharmaceutical Investigation
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    • v.40 no.6
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    • pp.379-386
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    • 2010
  • Mono PEGylated rhG-CSF (PEG-G-CSF) prepared by utilizing unique PEG was purified and characterized by cation-exchange chromatography. A unique, trimer-structured PEG was chosen for PEGylation of rhG-CSF among various PEG moieties. The in-vitro bioactivity, stability, and pharmacokinetics of mono-PEG-G-CSF were examined and compared to those of native rhG-CSF. Mono PEG-G-CSF exhibited reduced in-vitro bioactivity to native rhG-CSF but showed an excellent in-vivo bioactivity and stability. Furthermore, it showed markedly reduced clearance in rats, thereby increasing the biological half-life by about 4.5-fold compared to that of native rhG-CSF. The results suggest that this unique, trimer-structured 23 kDa PEG can provide advantages to improve the bioactivity of therapeutic proteins in clinical use.

Production of Soluble Recombinant Human Granulocyte Colony Stimulating Factor in E. coli by Control of Growth Rate. (대장균에서 증식속도 조절에 의한 수용성 재조합 인간 과립구 콜로니 촉진인자의 생산)

  • 박세철;고인영;강희일
    • Microbiology and Biotechnology Letters
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    • v.32 no.2
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    • pp.135-141
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    • 2004
  • Human granulocyte colony-stimulating factor (hG-CSF) is a hematopoiesis agent that principally affects the differentiation of neutrophils in the bone marrow. At present, recombinant hG-CSF is used successfully in the treatment of chemotheraphy-induced neutropenia and its indication has been expanded to bone marrow transplantation and aplastic anemia. In this study, we have constructed rhG-CSF secretion plasmid pYRC1 in which OmpA signal sequence/hG-CSF gene was expressed under the control of the T7 promoter. rhG-CSF produced in E. coli BL21 (pYRC1) grown at $37{\circ}C$ was found in aggregates. However, 15% of the periplasmic protein was soluble rhG-CSF when the E. coli BL21 (pYRC1) was cultured at $25^{\circ}C$ for 7 h in the modified MBL medium containing 10 g/$\ell$ glucose with 10 $\mu$M IPTG induction. The production of soluble rhG-CSF in E. coli BL21 (pYRC1) using fed batch culture was also studied. In the fed batch culture system, the final yield of rhG-CSF produced from E. coli BL21 (pYRC1) was increased from 4.4 mg/$\ell$to 24 mg/$\ell$by controlling the specific growth rate from $0.43 h^{-1}$ to $0.14 h^{-1}$, and optimizing the time of induction.

Local Irritation Test of HM10411 (rhG-CSF) in Rabbits (인과립구 콜로니 자극인자 제제인 HM10411 (rhG-CSF)의 국소자극성)

  • 차신우;한정희;김충용;서정은;김종춘;권세창
    • Biomolecules & Therapeutics
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    • v.10 no.3
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    • pp.170-174
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    • 2002
  • The local irritation study (skin and occular irritation tests) of HM10411, a rhG-CSF (recombinant human granulocyte-colony stimulating factor) was carried out in New Zealand White rabbits. HM10411 was applied to the bare skin at a dose of 2.5 mg/rabbit (5.0 mg/ml, 0.5 ml) and to the conjunctival sac of eye at a dose of 0.5 mg/rabbit (5.0 mg/ml, 0.1 ml) , respectively. In this study, there were no clinical signs which were related to HM10411 compared with those of control group. From above results, HM10411 has not any irritating activity to skin and eye in rabbits.

Mutagenicity Study of DA-3030, A New Recombinant Human G-CSF(rhG-CSF) (새로운 재조합 인 과립구 콜로니 자극인자 DA-3030의 변이원성연구)

  • 강경구;최성학;김옥진;안병옥;백남기;김계원;김원배;양중익
    • Biomolecules & Therapeutics
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    • v.2 no.3
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    • pp.286-291
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    • 1994
  • The mutagenicity of DA-3030(rhG-CSF)was studied by reverse mutation test, chromosome aberration test and micronucleus test. The reverse mutatuon test in bacteria was performed using salmonella typhimurium strain TA100, TA98, TA1535 and TA1537 with rhG-CSF in any of the concentrations(150, 75, 37.5, 18.75, 9.375 and 4,6875 $\mu\textrm{g}$/plate), no increase in the number of revertant colonies in each strain was observed, irrespective of treatment with the metabolic activation system(S-9 mix) The chromosome aberration test was carried out using CHL cells, cell line from chinese hamster lung. With 4 doses(75, 37.5, 18.75 and 9.375 $\mu\textrm{g}$/ml) of rhG-/CSF the cells were treated for 24 or 48 hours in the direct method or for 6 hours followed by 18 hour-expression time in the metabolic activation method. Results of the study showed, by the direct method or metabolic activation method, no trend toward increase in the number of aberrant metaphase. The micronucleus test was carried out using ICR mice at the age of 8 weeks. Three doses(862.5, 1725 and 3450 $\mu\textrm{g}$/kg) of DA-3030 were admintstered intraperitoneally with single shot and bone marrow cells were sampled at 24 hours after administration. Neither the number of polychromatic erythrocytes with micronuclei nor the ratio of normochromatic erythrocytes to polychromatic erythrocytes increased singinficantly in each dose, compared with a vehicle control. These results indicate that rhG-CSF has not mutagenic potential under the condiions.

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A Study of Peripheral Blood and Bone Marrow Responses Depends on the Frequency of rhG-CSF Administration in Dogs (개에서 재조합 과립구 자극 인자 (rh G-CSF)의 투여 간격에 따른 말초혈액과 골수의 반응에 대한 연구)

  • Kim, Ji-Hyun;Jee, Cho-Hee;Won, Jin-Hee;Jung, Hae-Won;Moon, Jong-Hyun;Cho, Kyu-Woan;Kang, Byeong-Teck;Jung, Dong-In
    • Journal of Veterinary Clinics
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    • v.31 no.2
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    • pp.77-84
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    • 2014
  • The present study evaluated that responses of peripheral and bone marrow depends on the frequency of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration in dogs. The rhG-CSF has been revealed that have a beneficial effect for dogs with myelosuppression secondary to chemotherapy or radiation but there were no studies about the frequency of administration in dogs. In this research, rhG-CSF was administrated $5{\mu}g/kg$ subcutaneously for each two-dogs group as follows: (1) every day for trial, (2) every other day for trial, (3) every third day for trial. The peripheral blood analysis including direct microscopic differential counts of one hundred cells was performed every day. Bone marrow aspiration was performed before administration of rh G-CSF, on the day of 0, 3, 9 and when the WBC counts were decreased within the normal range (day 12 or 13). Rh G-CSF was well-tolerated and showed no side effects in all dogs. According to the present study, $5{\mu}g/kg$ administration of rhG-CSF have cell-specific, frequency-related effect on bone marrow and peripheral blood. Furthermore, the effects of rhG-CSF administration on bone marrow sustained during the study and prolonged at least 3 days after discontinuing of rhG-CSF treatment.

General Pharmacology of Recombinant Human Granulocyte-colony Stimulating Factor DA-3030 Expressed in E. coli (유전자 재조합 인형 과립구 콜로니 자극인자 DA-3030의 일반약리작용)

  • 배은주;신명수;김순회;강수형;김원배;양중익
    • Biomolecules & Therapeutics
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    • v.2 no.3
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    • pp.281-285
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    • 1994
  • Neutropenia is a major dose-limiting factor in cancer chemotherapy diminishing its usefulness and increase patient's susceptibility to infectious disease. Some recombinant human granulocyte colony stimulating factors(rhG-CSFs) are in use to reduce the risk of this serious side effect. In this study, we examined the pharmacological properties of DA-3030, a rhG-CSF expressed in E. coli. DA-3030 100 and $\mu\textrm{g}$/kg, i. v., had no significant effect on the central nervous, gastrointestinal system in mice and cardiovascular system in rabbits, but it slightly inhibited the spontaneous motility of isolated nonpregnant uterus in rats. It also had no influence on excretion of urinary electrolytes. DA-3030 administered for successive 3 days increased the blood WBC count in zymosan air pouch inflammed rats and in normal rats. These results indicate that DA-3030 has little side effects in animals.

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Effects of Recombinant truman Granulocyte Colony-Stimulating Factor(rhG-CSF) on Cyclophosphamide-induced Neutropenic Mice (호중구 감소증을 유도한 마우스에서의 유전자 재조합 인과립구 콜로니자극인자의 효과)

  • 조명행;유아선;방명주;곽형일;성하정;안길환
    • Biomolecules & Therapeutics
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    • v.6 no.2
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    • pp.145-150
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    • 1998
  • Administration of 3 type KGCs [recombinant human granulocyte colony-stimulating factor (rhG-CSF)] to mice with cyclophosphamide (CPA)-induced neutropenia for 4 consecutive days from the day after the CPA dosing (100 mg/kg) resulted in a dose dependent increase in the peripheral blood neutrophil count 6 hours after the final KGC injection. Within the KGC dose range of 0.1 to 40$\mu$g Per mouse Per day, there was a sigmoidal relationship between the logarithm of the dose and the peripheral blood neutrophil count (relative value for neutrophil count of the basal dose) in the treated mice. The sigmoidal relationship of test KGC preparations shows that there is a saturation point in terms of efficacy. Compared with e(fact of KGC-Orange, Green, and Blue, KGC-Orange recovers neutrophils more effectively than the others do.

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Synthesis of Dithiolopyrrolone Derivatives and Their Leukocyte-Increasing Activities

  • Li, Chungang;Sun, Yiping;Wang, Guoping;Tan, Xiangduan
    • 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.