• Biomolecules & Therapeutics
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• v.3 no.4
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• pp.251-255
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• 1995

DA-3002 is a genuine human growth hormone produced by Dong-A Pharm. Co. Ltd. research laboratory using recombinant DNA technic. In this study, antigenic potential of DA-3002 was examined by active systemic anaphyaxis(ASA) in guinea pigs, mouse-rat passive cutaneous anaphylaxis(PCA) and passive hemagglutination(PHA) test as a part of safety research. DA-3002 induced anaphylactic shock in ASA test using guinea pigs Immunized with DA-3002 alone or DA-3002 incoporated into Freund's complete adjutant(FCA) when challenged with 10 times higher dose of anticipated clinical dose of DA-3002. In the mouse-rat PCA and PHA test, DA-3002 also showed positive results. DA-3002, therfore, was considered to produce IgE, IgG, and/or IgM in mice. The results of this study were similar to those of the other human growth hormones and these positive results were thought to be caused due to the fact that both DA-3002 and the other human growth hormones were heterogenous proteins to guinea pigs and mice. Considering the fact that DA-3002 is a genuine human growth hormone of which structure is identical with indigenous human growth hormone, DA-3002 is thought not to cause immunological problems in clinical use.

• Biomolecules & Therapeutics
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• v.3 no.1
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• pp.63-71
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• 1995

The local irritation studies of DA-3002, an authentic recombinant human growth hormone (rhGH), were carried out in rabbits after the following treatment ; application into the conjunctival sac of the eye (single), single subcutaneous and intramuscular injection, 7-day repeated subcutaneous and intramuscular injection. The results obtained were as follows. In the result of ocular irritation test, 0.16% solution of DA-3002 could be considered as a non-irritating material. In single subcutaneous and intramuscular irritation test, the irritancy of 0.16% DA-3002 solution was not so much different from that of saline. The local irritation of DA-3002 by 7-day repeated injection was negligible and similar to that of saline by both subcutaneous and intramuscular routes. These results suggest that DA-3002 has no irritating activity when injected through subcutaneous or intramuscular route for clinical practice as 0.16% solution.

• Biomolecules & Therapeutics
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• v.3 no.4
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• pp.294-300
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• 1995

DA-3002, an authentic recombinant human growth hormone(rhGH), was examined for mutagenicity in the reverse mutation test on bacteria, in the chromosomal aberration test on cultured mammalian cells and in the micronucleous test on mice. The reverse mutation test was performed by a plate incorporation method with or without a metabolic activation system(S9 Mix) using Salmonella typhimurium strain TA100, TA1535, TA98 and TA1537. DA-3002 did not significantly increase revertant colonies in any of the test strains under any conditions at dose levels ranging from 0.0125 to 0.4 IU/plate, compared with the vehicle control. In the chromosomal aberration test using cultured Chinese hamster lung(CHL) cells, DA-3002 did not increase the number of aberrant cells in the presence or absence of S9 mix at concentrations of 0.0125 IU/mι to 0.4 IU/mι, compared with the vehicle control. In the micronucleus test, male ICR mice were given DA-3002 intraperitoneally at a dose level of 20, 40 and 80 lU/kg. The incidence of bone marrow micronucleated polychromatic erythrocytes in the DA-3002 treated mice did not differ from that of the vehicle control. These results indicate that DA-3002 doesn't have mutagenic potential under the present test conditions.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.161-172
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• 1994

This study was conducted to examine DA-3002, a biosynthetic human growth hormone, for its acute and subacute toxicities in mice and rats. The drug was administered subcutaneously and orally at a dose level of 1.0, 3.0, 8.9, 26.7 or 80.0 lU/kg once for single dose toxicity and given subcutaneously at a dose level of 0.34, 1.7 or 8.4 lU/kg daily for 13 weeks to investigate repeated dose toxicity. In the acute toxicity study, doses up to 80 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal changes which could be attributed to toxic effect of DA-3002. In the subacute toxicity study, the growth hormone was tolerated well in broth mice and rats. No drug related deaths occurred and all animals appeared to be normal throughout the dosing period. Increases in body weight gain, food utilisation and absolute organ weights were observed in the rats in the high dose group. Mild changes in the blood chemical parameters were also seen in the treated groups. Histopathologically, however, no abnormal changes were observed in any organ. The changes noted during the treatment periods presumably represent exaggerated pharmacological effects of the growth hormone, and no observed adverse effect level (NOAEL) was considered to be more than 8.4 lu/kg/day.