Treatment or prevention of hypertensive disorders of pregnancy or fetal growth retardation
The present invention relates to the use of a steroid in the manufacture of a pharmaceutical composition for use in the therapeutic or prophylactic treatment of a hypertensive disorder of pregnancy (HDP) or fetal growth retardation, said treatment comprising administering to a female mammal a steroid selected from the group consisting of: substances represented by the following formula (formula I) in which formula R 1 , R 2 , R 3 , R 4 independently are a hydrogen atom, a hydroxyl group or an alkoxy group with 1-5 carbon atoms; each of R 5 , R 6 , R 7 is a hydroxyl group; no more than 3 of R 1 , R 2 , R 3 , R 4 are hydrogen atoms; precursors of such substances; and mixtures of one or more of the aforementioned substances and/or precursors.
1. A method of treating a hypertensive disorder of pregnancy (HDP) or fetal growth retardation, said method comprising administering to a female mammal a steroid selected from the group consisting of:
(a) substances represented by the following formula
in which formula R 1 , R 2 , R 3 , R 4 independently are a hydrogen atom, a hydroxyl group or an alkoxy group with 1-5 carbon atoms; each of R 5 , R 6 , R 7 is a hydroxyl group; no more than 3 of R 1 , R 2 , R 3 , R 4 are hydrogen atoms;
(b) precursors capable of liberating a substance according to the aforementioned formula when used in the present method, which precursors are derivatives of the aforementioned steroids wherein the hydrogen atom of at least one of the hydroxyl groups has been substituted by an acyl radical of a hydrocarbon carboxylic, sulfonic or sulfamic acid of 1-25 carbon atoms; tetrahydrofuranyl; tetrahydropyranal; or a straight or branched chain glycosidic residue containing 1-20 glycosidic units per residue; and
(c) mixtures of one or more of the aforementioned substances and/or precursors.
2. The method according to claim 1 , wherein R 3 represents a hydroxyl group or an alkoxy group.
3. The method according to claim 1 , wherein at least 3 of the groups R 1 , R 2 , R 3 and R 4 represent hydrogen atoms.
4. The method according to claim 1 , wherein the hypertensive disorder of pregnancy is selected from the group consisting of preeclampsia, eclampsia, HELLP syndrome and gestational hypertension.
5. The method according to claim 3 , wherein the hypertensive disorder of pregnancy is preeclampsia.
6. The method according to claim 3 , wherein the steroid is administered within 24 hours of diagnosis of hypertension.
7. The method according to claim 1 , wherein the administering is intravenous, intravaginal, rectal, subcutaneous, intramuscular, intra-uterine or oral.
8. The method according to claim 1 , wherein the female mammal is pregnant.
9. The method according to claim 7 , wherein the female mammal is at least 20 weeks pregnant.
10. The method according to claim 1 , wherein the treatment does not comprise co-administration of progestogens, cyclooxygenase inhibitors, nitric oxide donors, nitric oxide substrates, endothelin antagonist, endothelin synthase inhibitor, prostacyclin, prostacylin analog, citrulline or citrulline analog.
11. The method according to claim 9 , wherein the treatment does not comprise co-administration of another pharmaceutically active component besides the steroid.
12. The method according to claim 1 , wherein the steroid is administered in a dosage of at least 2.5 μg per kg of bodyweight.
13. The method according to claim 11 , wherein the steroid is administered in a dosage of at least 5 μg per kg of bodyweight.
14. A method of lowering the risk of a hypertensive disorder of pregnancy (HDP) or fetal growth retardation, comprising administering to a female mammal a steroid selected from the group consisting of:
(a) substances represented by the following formula
in which formula R 1 , R 2 , R 3 , R 4 independently are a hydrogen atom, a hydroxyl group or an alkoxy group with 1-5 carbon atoms; each of R 5 , R 6 , R 7 is a hydroxyl group; no more than 3 of R 1 , R 2 , R 3 , R 4 are hydrogen atoms;
(b) precursors capable of liberating a substance according to the aforementioned formula when used in the present method, which precursors are derivatives of the aforementioned steroids wherein the hydrogen atom of at least one of the hydroxyl groups has been substituted by an acyl radical of a hydrocarbon carboxylic, sulfonic or sulfamic acid of 1-25 carbon atoms; tetrahydrofuranyl; tetrahydropyranal; or a straight or branched chain glycosidic residue containing 1-20 glycosidic units per residue; and
(c) mixtures of one or more of the aforementioned substances and/or precursors.
15. The method according to claim 14 , wherein the hypertensive disorder of pregnancy is selected from the group consisting of preeclampsia, eclampsia, HELLP syndrome and gestational hypertension.