Methods for using LHRH antagonists with low histamine release

US5763404A · kind A · utility

Inventors

• Karl Folkers · Austin, US
• Cyril Y. Bowers · New Orleans, US
• Anders Ljungqvist · Austin, US
• Pui-Fun L. Tang · Sha Tin, CN
• Minoru Kubota · Austin, US
• Dong-Mei Feng · Harleysville, US

Key dates

• Filing date: Jun 6, 1995
• Grant date: Jun 9, 1998
• Expiry date: Jun 6, 2015

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y10S930/13
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Antide is the decapeptide, N-Ac-D-2-Nal,D-pClPhe, D-3-Pal, Ser,NicLys, D-NicLys, Leu, ILys, Pro, D-Ala,NH.sub.2 which is an antagonist of luteinizing hormone releasing hormone (LHRH). This decapeptide, like others of the present invention, has high antiovulatory activity (AOA) and releases negligible histamine. Antide is scheduled for scale-up, safety testing and evaluation in the experimental primate and in clinical medicine. Numerous other peptides having structures related to Antide were prepared and tested. These peptides had variations primarily in positions 5, 6, 7, and 8. Of these, N-Ac-D-2-Nal, D-pClPhe,D-3-Pal,Ser,PicLys,cis-DPzACAla,Leu,ILys,Pro,D-Ala-NH.sub.2 was one of the most potent and had higher antiovulatory activity than Antide, i.e. 73%/0.25 ug and 100%/0.5 ug vs. 36%/0.5 ug and 100%/1.0 ug. Antide showed significant, (p<0.001) duration of action, when injected at a dose of 10 ug, 44 hours before 50 ng of the agonist, D-3-Qal.sup.6 !-LHRH. Antide showed oral AOA at 600 ug (73%) and at 1200 ug (100%) with negligible difference being found between water and corn oil oral formulations. In the antagonists prepared according to the present invention, arginine and its …