Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1997-05-28
1999-07-13
Tsang, Cecilia J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
530399, A61K 3830, C07K 1465
Patent
active
059226730
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a method of treating high blood pressure or a tendency to be hypertensive in pregnant mammals including humans which aids fetal development.
BACKGROUND ART
Hypertension in pregnancy is, both in man and in other mammals, associated with impaired fetal growth. In man it is frequently associated with a syndrome of proteinuria and edema which is termed "toxaemia of pregnancy" or preeclampsia These pregnancies are complicated by insufficiency and fetal growth retardation. Current therapy is essentially restricted to common anti-hypertensive agents and bed rest which, while reducing the risk of hypertensive crises in the mother, do not correct the fetal growth retardation and reduce the consequent risk of fetal death, stillbirth and the neonatal complications of intrauterine growth retardation. The essence of this invention is that we have found that the administration of IGF-1 in pregnant hypertensive mammals reduces maternal blood pressure and improves placental function and fetal development.
We have previously disclosed that the administration of IGF-1 through part or whole of pregnancy to a maternal mammal overcomes maternal constraint on fetal growth (IGF-1 in Pregnancy: PCT Europe 91912874.4, USA 07/969229, Japan 3-511969, Australia 82052/91, Canada 2087030). We have observed such administration of IGF-1 promoting fetal growth and placental function. However there is nothing in the prior art that would have led us to conclude that there would be a lowering effect on blood pressure. Elsewhere we have disclosed that in non-pregnant animals IGF-1 promotes cardiac output (Ambler et al J Cardiovascular Research 27 1368-1373 1993) and this is associated with maintenance of blood pressure.
In pregnant mammals with hypertension and a predisposition to give birth to growth retarded fetuses with disproportionately large placentas, we have now observed that IGF-1 administration to the mother reverses these changes.
SUMMARY OF INVENTION
In a first aspect the present invention consists in a method of treatment by which IGF-1 is administered to pregnant mammals with hypertension to promote fetal growth and placental function.
In a further aspect the invention consists in a method of treatment by which IGF-1 is administered to pregnant mammals with hypertension to reduce maternal blood pressure.
In still a further aspect the invention consists in a method of treatment by which maternal levels of IGF-1 are elevated either directly by administration of IGF-1 or indirectly by the admission of other hormones which elevate mammal IGF-1 such as growth hormone.
In yet a further aspect the invention consists in a method of treatment where preferably the IGF-1 administered is recombinant human IGF-1 or one of its analogues with alterations to the amino terminal (eg des 1-3 N IGF-1).
In yet a further aspect the invention consists in a method of treatment where the IGF-1 may be administer alone or in combination with binding proteins to alter its half life and bioavailability or in combination with growth hormone.
In still after aspect the present invention consists in a method of treatment where IGF-1 is administered during the latter phase of pregnancy when hypertension is present.
In yet a further aspect the invention consists in a method of treatment where IGF-1 is administered at a dose of 40 to 2000 .mu.g/kg body weight per day to a pregnant mammal and preferentially in humans at a dose of 40 to 200 .mu.g/kg/body weight per day.
In yet a further aspect the invention consists in a mode of treatment by which the IGF-1 is administered to a pregnant mammal either continuously by implant or intermittently by subcutaneous or intramuscular, intranasal or oral routes of administration.
In still a further aspect the invention consists in a method of treatment where preferably IGF-1 itself is administered subcutaneously but forms of IGF-1 with increased stability may be given by oral or intranasal route.
In yet a further aspect the invention consists in a mode of treatment where
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Bassett Nicole Susan
Gluckman Peter David
Johnston Barbara Madeleine
Chiron Corporation
Gupta Anish
Tsang Cecilia J.
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