Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1994-02-17
1996-01-09
Warden, Jill
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 21, 530303, 530399, A61K 3800, C07K 1300
Patent
active
054829267
DESCRIPTION:
BRIEF SUMMARY
The present invention; relates to the use of IGF-II or effective analogues thereof for the manufacture of a medicament for prevention or treatment of nutritional or gastrointestinal disorders and for promoting human or animal neonatal growth. It also relates to composition comprising exogenous human or animal IGF-II or effective analogues thereof in a therapeutically effective amount together with a pharmaceutically acceptable carrier or diluent or foodstuff, preferably in admixture with artificial or natural milk or colostrum. The invention may be applied both in man and in animals.
INTRODUCTION AND PRIOR ART
Insulin-like growth factor 2 (IGF-II) is a peptide present in plasma and other body fluids. Its primary sequences shows 64% homology to IGF-I and comprises 67 amino acids, including 3 disulphide bonds. It can stimulate growth of a wide range of cell types. IGF-II have been purified from human plasma and the complete amino acid sequence is known. Sequences with extensive homologies to human IGF-II are present in IGF-II purified from plasma of other species. IGF-II has systemic and local effects and appear mostly associated with different specific binding problems, six of which are sequenced and are termed IGFBP1, IGFBP2, IGFBF3, IGFBP4, IGFBP5 and IGFBP6. These appear to modulate the biological functions and availability of IGF-II in both a positive and negative manner. IGF-II appears to act mainly by interactions with the IGF-type 1 receptor exposed on the outer surface of plasma membranes in many different cell types--however relative specificity of action rosy be found because of the influence of binding proteins. IGF-II may also have distinct actions as it binds to a distinct and unrelated type 2 receptor also found on cell membranes. Moreover, binding of IGF-II to insulin receptors also seems to be of importance. Because of the scarcity of purified plasma IGF-II there was a great necessity to develop methodology for the commercial scale production of IGF-II. Nowadays such large scale production can readily be achieved by using recombinant DNA techniques. IGF-II has been shown to experimentally reduce the catabolic state in starved animals and to antagonise some metabolic actions of IGF-I (Koea et al Endocrinology 1992, 130, 2423-2425). These observations of Koea et al plus the different range of receptor specificities of IGF-II to that of IGF-I mean that there is no obviousness to any action of IGF-II on the gastrointestinal tract.
It has previously been demonstrated that both type I and type 2 IGF receptors are present in the gastrointestinal tract and that oral IGF-I and IGF-II affect jejunal enzymes following repeated administration in older suckling rats, but no effect on intestinal growth was observed. (Young et al. Digestion 46, (1990), Suppl. 2, 240-252). Ballard et al , WO 91/12018 have disclosed the therapeutic use of IGF-I for gastrointestinal disease or the treatment of the shortened gut after surgery. Ballard provide no evidence of activity following oral administration.
Heinze-Erian et al, Endocrinology, (1991) Vol 129, No 4, 1769, reports that there is an essential role for both IGF receptors in the regulation of cell mitogenesis and growth.
Grey Vet al, Mol-Cell-Endocrinol, 1991, Mar, Vol 75 (3), 221-7 suggests that IGF-II/man-6-P receptor may play a role in the adaptive regenerative response of the intestinal epithelium.
There was however not a priori reason to believe that IGF-II might be efficacious in the normal gut in the premature or immediately neonatal gut and the prior art does not demonstrate any known action of IGF-II on the gastrointestinal system.
No studies of the effects of oral administration of the IGF-II on the neonatal gastrointestinal system, nutritional status or growth have been previously suggested.
There is a need for a medicament for prevention or treatment of nutritional or gastrointestinal disorders.
It has now surprisingly been found that IGF-II or effective analogues thereof can be used for the manufacture of such a medicament which also can be used
REFERENCES:
Heinz-Erian et al., Eudocmnology, 1991 p. 1769.
Shober et al., Endocruology, vol. 126(2), Feb. 1990, pp. 1125-1132.
Young, et al., Insulin-Like Growth Factors and the Developing and Mature Rat Small Intestine: Receptors and Biological Actions, Digestion, 1990, (46, Supplement 2), pp. 240-252.
Dialog Information Services, File 155, Medline, Dialog No. 07566682 1966-1994.
Grey, et al., Insulin-like Growth Factor II/Mannose-t-Phosphate Receptors Are Transiently Increased in the Rat Distal Intestinal Epithelium After Resection, Molecular and Cellular Endocrinology, 1991 (75), pp. 221-227.
Heinz-Erian, et al., Identification and In Situ Localization of the Insulin-Like Growth Factor-II, Endocrinology, 1991, p. 1769.
Rivard, et al., Negative Control by Sandostatin on Pancreatic and Doudenal Growth: A Possible Implication of Insulin-Like Growth Factor I, Regul-Pept., 1991, Jun. 11, vol. 34 (11), PP. 13-23 (Abstract).
Koenuma, et al., Insulin and Insulin-Like Growth Factor 1 Stimulate Proliferation of Metastatic Variants of Colon Carcinoma 26, Japan J. Cancer Res. 1989, Jan., vol. 80(1), pp. 51-58 (Abstract).
Culouscou, et al., Purification of a Colon Cancer Cell Growth Inhibitor and its Identification as an Insulin-Like Growth Factor Binding Protein, Cancer Res. 1991, Jun. 1, vol:51(11), pp. 2813-2819 (Abstract).
Gluckman Peter D.
Mellor David J.
Pharmacia AB
Touzeau P. Lynn
Warden Jill
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