Complex of human growth hormone and zinc and use

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Hormones – e.g. – prolactin – thymosin – growth factors – etc.

Reexamination Certificate

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C530S399000, C530S839000, C514S012200, C514S021800, C424S423000, C424S426000, C424S502000, C424S489000, C424S494000, C424S641000, C424S078310, C424S078340

Reexamination Certificate

active

06429296

ABSTRACT:

The present invention relates to a complex of human growth hormone and zinc containing human growth hormone and zinc at a molar ratio of about 1:1.6 to about 1:2.4, a sustained-release preparation which comprises the complex of human growth hormone and zinc and a biodegradable polymer, and so on.
BACKGROUND ART
In recent years, human growth hormone (hereinafter abbreviated as GH) has been produced on a large scale by utilizing genetic engineering technology, and is used widely, for example, being clinically applied to Turner's syndrome, infantile chronic renal diseases, achondroplasia and adult GH hyposecretion as well as pituitary dwarfism. Further, applications for osteoporosis in an aging society and static heart diseases are expected.
Since GH is usually administered by intramuscular or subcutaneous injection repeatedly and over a long term, due to consideration of stability in the body, a significant physical burden on patients is a problem. For instance, in the case of pituitary dwarfism, a daily subcutaneous administration to infants or young patients over a long period of time ranging from a few months to at least 10 years is practiced. On the one hand, development of a sustained-release preparation containing GH, which is medicinally effective with an administration ranging from once every few weeks to few months, has been reported (S.T.P. Pharma. Sci., 4(6), pages 437-441, 1994; Nature Med., 2(7), pages 795-799, 1996; J.Pharm.Exp.Ther., 281, pages 1431-1439, 1997,; WO 94/12158; WO 95/29664; WO 97/01331).


REFERENCES:
patent: 5654010 (1997-08-01), Johnson
patent: 6191107 (2001-02-01), Yamagata
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patent: 94/12158 (1994-06-01), None
patent: 95/29664 (1995-11-01), None
patent: 96/07399 (1996-03-01), None
patent: WO92/17200 (1996-10-01), None
patent: 96/40072 (1996-12-01), None
patent: WO96/40074 (1996-12-01), None
patent: 97/01331 (1997-01-01), None
patent: WO97/03692 (1997-02-01), None
patent: 98/27980 (1998-07-01), None
O. L. Johnson et al., “A month-long effect from a single injection of microencapsulated human growth hormone”, Nature Medicine, vol. 2, No. 7, pp. 795-799, Jul. 1996.
R. B. Aisina et al., “Microencapsulation of somatotropic growth hormone”, S.T.P. Pharma Sciences, vol. 4, No. 6, pp. 437-441, 1994.
H. Lee et al., “In vivoCharacterization of Sustained-Release Formulations of Human Growth Hormone”, The Journal of Pharmacology and Experimental Therapeutics, vol. 281, No. 3, pp. 1431-1439, 1997.

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