METHOD AND PHARMACEUTICAL COMPOSITION FOR INHIBITING PREMATURE RAPTURE OF FETAL MEMBRANES, RIPENING OF UTERINE CERVIX AND PRETERM LABOR IN MAMMALS

• US 20090081206A1
• Filed: 12/02/2008
• Published: 03/26/2009
• Est. Priority Date: 11/24/1997
• Status: Abandoned Application

• Current Assignee: Shamir Leibovitz
• Original Assignee: Shamir Leibovitz
• Inventors: Leibovitz, Shamir
• Application Number:
  US12/326,121
• Publication Number:
  US 20090081206A1
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 38/4813 Exopeptidases (3.4.11. to 3.4.19)
• CPC Class Codes: A61K 38/57 from animals; from humans A61K38/553, A61K38/556 take precedence
• CPC Class Codes: C07K 16/244 Interleukins [IL]

Abstract

A method and a pharmaceutical composition for inhibiting premature rapture of the fetal membranes, ripening of the uterine cervix and preterm labor of female mammals including human. The method includes the step of administering compounds for reversing at least two biochemical conditions being associated with the above processes. The pharmaceutical composition includes compounds for reversing at least two biochemical conditions being associated with the above processes.

Claims

1. A method of treating or preventing premature ripening of the cervix, premature rupture of fetal membranes and preterm labor in a pregnant female comprising administering to the pregnant female:

N-acetyl-cysteine; and

a compound for reversing a low ratio of progesterone effect versus estrogen effect;

thereby treating or preventing premature ripening of the cervix, premature rupture of fetal membranes and/or preterm labor in the pregnant female mammal.

2. The method of claim 1, wherein said compound for reversing said low ratio of progesterone effect versus estrogen effect is selected from the group consisting of progesterone, a progesterone receptor agonist and an estrogen receptor antagonist.

3. The method of claim 1, further comprising administering a conventional treatment for preventing ripening of the cervix and preterm labor.

4. The method of claim 3, wherein said conventional treatment is selected from the group consisting of treatment with MgSO₄, beta mimetic, Ca blocker, Atosiban and antibiotics.

5. The method of claim 4, wherein said beta mimetic is selected from the group consisting of salbutamol and ritodrin.

6. The method of claim 1, wherein said administration for said N-acetyl-cysteine and/or said compound is effected via a route selected from the group consisting of subcutaneously, intravenously, intramuscularly, orally, intracervically, intramniotically, extramniotically and intravaginally.

7. The method of claim 1, wherein said N-acetyl-cysteine and/or said compound are administered in a form selected from group consisting of cream, ointment, gel, liquid, spray, powder, pill, suppository, capsule and patch.

8. A pharmaceutical composition for treating or preventing premature ripening of the cervix, premature rupture of fetal membranes and/or preterm labor in a pregnant female pharmaceutical composition comprising, as active ingredients, N-acetyl-cysteine and a compound for reversing a low ratio of progesterone effect versus estrogen effect, the pharmaceutical composition further comprising a pharmaceutically acceptable carrier.

9. The pharmaceutical composition of claim 8, wherein said compound for reversing a low ratio of progesterone effect versus estrogen effect is selected from the group consisting of progesterone, a progesterone receptor agonist and an estrogen receptor antagonist.

10. The pharmaceutical composition of claim 8, further comprising a compound used in conventional treatment for preventing ripening of the cervix and preterm labor.

11. The pharmaceutical composition of claim 10, wherein said compound used in conventional treatment is selected from the group consisting of MgSO₄, beta mimetic, Ca blocker, Atosiban and antibiotics.

12. The pharmaceutical composition of claim 10, wherein said beta mimetic is selected from the group consisting of salbutamol and ritodrin.

13. The pharmaceutical composition of claim 8, formulated for intravenous administration.

14. The pharmaceutical composition of claim 8, formulated for intravaginal administration.

15. The pharmaceutical composition of claim 8, formulated as a cream, ointment, gel, liquid, spray, powder, pill, suppository, capsule or patch.

16. A method of treating or preventing premature ripening of the cervix, premature rupture of fetal membranes and preterm labor in a pregnant female comprising administering to the pregnant female:

an inhibitor of cervical collagenase; and

a compound for reversing a low ratio of progesterone effect versus estrogen effect;

thereby treating or preventing premature ripening of the cervix, premature rupture of fetal membranes and/or preterm labor in the pregnant female mammal.

17. The method of claim 16, wherein said inhibitor of cervical collagenase is selected from a group consisting of caffeic acid, hydroxyquinoline, collagenase-inhibiting hydroxyquinoline derivative, phosphonepeptide, bencarbonyl-specified peptide sequence, a collagenase-inhibiting peptide sequence, anticollagenase antibodies, a collagenase-inhibiting tripeptide hydroxamic acid derivative, CaNa₂EDTA, alpha-2-macroglobulin, alpha-1-antitrypsin, a metalloprotease inhibitor, a cysteine proteinase inhibitor, N-acetyl-cysteine, N-acetylhomocysteine, N,N′

-diacetylcysteine, L-arginine, guanido-substituted arginines or homoarginines, a collagenase inhibiting L-arginine N^G alkyl derivative, glycerol trinitrate and tissue inhibitor of matrix protease.

19. The pharmaceutical composition of claim 17, wherein said inhibitor of cervical collagenase is selected from a group consisting of caffeic acid, hydroxyquinoline, collagenase-inhibiting hydroxyquinoline derivative, phosphonepeptide, bencarbonyl-specified peptide sequence, a collagenase-inhibiting peptide sequence, anticollagenase antibodies, a collagenase-inhibiting tripeptide hydroxamic acid derivative, CaNa₂EDTA, alpha-2-macroglobulin, alpha-1-antitrypsin, a metalloprotease inhibitor, a cysteine proteinase inhibitor, N-acetyl-cysteine, N-acetylhomocysteine, N,N′

-diacetylcysteine, L-arginine, guanido-substituted arginines or homoarginines, a collagenase inhibiting L-arginine N^G alkyl derivative, glycerol trinitrate and tissue inhibitor of matrix protease.

18. A pharmaceutical composition for treating or preventing premature ripening of the cervix, premature rupture of fetal membranes and/or preterm labor in a pregnant female pharmaceutical composition comprising, as active ingredients, an inhibitor of cervical collagenase and a compound for reversing a low ratio of progesterone effect versus estrogen effect, the pharmaceutical composition further comprising a pharmaceutically acceptable carrier.