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Details for Patent: 4,743,589

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Details for Patent: 4,743,589

Title: Treatment of endometriosis
Abstract:A novel method of treating prostate adenocarcinoma, prostate benign hypertrophia, endometriosis, dysmenorrhea, hirsuitism, hormono-dependant mammary tumors, treatment and prevention of precocious puberty, induction of a retardation of the appearance of puberty and treatment of acne of mammals comprising administering to warm-blooded animals an effective amount of a peptide of the formula wherein (a) Z is Gly-NH.sub.2, Y is Leu and X is Gly, (b) Z is Gly-NH.sub.2, Y is Leu, X is DN Leu, DN Val, D Abu (.beta.-aminobutyric acid), D Phe, D Ser, D Thr, D Met, D Pgl, D Lys, Leu, Ile, Nle, Val, N Val, Met, Phe, D Leu, D Arg, D Ser (tbu), D Thr (tbu), D Cys (tbu), D Asp (O tbu), D Glu (Otbu), D Orn (boc), D Lys (boc), D Trp, Trp, 2-methyl Ala, D Tyr, .epsilon.lauryl -D Lys, .epsilon.-dextran-D Lys, (c) Z is NH-cyclopropyl-or NH-Alk wherein Alk is alkyl or 1 to 3 carbon atoms, Y is Leu and X is D Ser (tbu), D Thr (tbu), D Asp (Otbu), D Glu (Otbu), D Orn (boc), D Lys (boc), (d) Z is --NH--CH.sub.3, --NH--CH.sub.2 --CH.sub.3, NH--CH.sub.2 --CH.sub.2 --CH.sub.3, --NH--CH.sub.2 --CH.sub.2 --OH, ##STR1## Y is Leu and X is Gly, (e) Z is --NH--CH.sub.2 --CH.sub.3, Y is Leu and X is D Trp, D Leu, D Ala, D Ser (tbu), D Tyr, D Lys, Ala, (f) Z is Gly-NH.sub.2 or --NH--CH.sub.2 --CH.sub.3, Y is N.alpha.Me Leu and X is Gly, (g) Z is --NH--cyclopropyl, Y is Leu and X is D Leu or (h) Z is Gly-NH.sub.2, --NH-cyclopropyl or -NHAlk' where Alk' is alkyl of 1 to 3 carbon atoms, Y is Ser (but), Cys (but), Asp (Obut), Glu (Obut), Orn (boc), Lys (boc) and X is Gly.
Inventor(s): Labrie; Fernand (Quebec, CA), Raynaud; Jean-Pierre (Paris, FR)
Assignee: Roussel UCLAF (Paris, FR)
Filing Date:Jun 18, 1984
Application Number:06/621,421
Claims:1. A method for the treatment of endometriosis in female mammals consisting essentially of administering to female mammals an amount of a peptide of the formula

wherein (a) Z is Gly-NH.sub.2, Y is Leu and X is Gly, (b) Z is Gly-NH.sub.2, Y is Leu, X is DN Leu, DN Val, D Abu (.alpha.-aminobutyric acid), D Phe, D Ser, D Thr, D Met, D Pgl, D Lys, Leu, Ile, Nle, Val, N Val, Met, Phe, D Leu, D Arg, D Ser (tbu), D Thr (tbu), D Cys (tbu), D Asp (O tbu), D Glu (Otbu), D Orn (boc), D Lys (boc), D Trp, Trp, 2-methyl Ala, D Tyr, .epsilon.-lauryl-D Lys, a-dextran-D Lys, (c) Z is NH-cyclopropyl-or NH-Alk wherein Alk is alkyl of 1 to 3 carbon atoms, Y is Leu and X is D Ser (tbu), D Thr (tbu), D Asp (Otbu), D Glu (Otbu), D Orn (boc), D Lys (boc), (d) Z is --NH--CH.sub.3, --NH--CH.sub.2 --CH.sub.3, NH--CH.sub.2 --CH.sub.2 --CH.sub.3, --NH--CH.sub.2 --CH.sub.2 --OH, ##STR3## Y is Leu and X is Gly, (e) Z is --NH--CH.sub.2 --CH.sub.3, Y is Leu and X is D Trp, D Leu, D Ala, D Ser (tbu), D Tyr, D Lys, Ala, (f) Z is Gly-NH.sub.2 or --NH--CH.sub.2 --CH.sub.3, Y is N.alpha.Me Leu and X is Gly, (g) Z is --NH--cyclopropyl, Y is Leu and X is D Leu or (h) Z is Gly--NH.sub.2, --NH--cyclopropyl or NHAlk' wherein Alk' is alkyl of 1 to 3 carbon atoms, Y is Ser (but), Cys (but), Asp (Obut), Glu (Obut), Orn (boc), Lys (boc) and X is Gly sufficient to treat endometriosis.

2. The method of claim 1 wherein Z is --NH--CH.sub.2 --CH.sub.3, Y is Leu and X is D Trp, D Leu, D Ala, D Ser (tbu), D Tyr, D Lys, Ala.

3. The method of claim 1 wherein the peptide is [D Ser (tub).sup.6 des Gly NH.sub.2.sup.10 ] LH-RH ethylamide.

4. The method of claim 1 wherein the peptide is [D Ser (tbu).sup.6 des Gly NH.sub.2.sup.10 ]LH-RH ethylamide and is administered parenterally at a daily dose of 10 to 200 .mu.g.

5. The method of claim 1 wherein the peptide is [D Ser (tbu).sup.6 des Gly NH.sub.2.sup.10 ]LH-RH ethylamide and is administered intranasally at a daily dose of 100 to 2000 .mu.g.

6. The method of claim 4 wherein the peptide is administered once or twice a day each day.

7. The method of claim 5 wherein the peptide is administered once or twice a day each day.

8. The method of claim 4 wherein the peptide is administered once or twice a day with intervals of several days.

9. The method of claim 5 wherein the peptide is administered once or twice a day with intervals of several days.

10. A method for the treatment of endometriosis in female mammals consisting essentially of administering to female mammals an amount of [D Ser (tbu).sup.6 des Gly NH.sub.2.sup.10 ]LH-RH ethylamide sufficient to treat endometriosis.
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