Intranasal administration of polypeptides in powdered form

Abstract

Pharmaceutical compositions or biologically active polypeptides in powder form suitable for nasal administration, comprising a therapeutically effective amount of a biologically active polypeptide and a water-soluble polysaccharide.

1 - 10 . (canceled)  
     
     
         11 . A powdered pharmaceutical composition for the intranasal administration of an LHRH analogue selected from the group consisting of 
 N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-D-Tyr-Leu-Deh-Pro-D-AlaNH 2 ;    N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-D-Tyr-Leu-Mbh-Pro-D-AlaNH 2 ;    N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-D-Tyr-Leu-Bth-Pro-D-AlaNH 2 ;    N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Tyr-D-Tyr-Leu-Pha-Pro-D-AlaNH 2 ;    N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Nal(2)-Leu-Deh-Pro-D-AlaNH 2 ;    N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Nal(2)-Leu-Mbh-Pro-D-AlaNH 2 ;    N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Nal(2)-Leu-Bth-Pro-D-AlaNH 2 ;    N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Nal(2)-Leu-Pha-Pro-D-AlaNH 2 ;    N-Ac-D-Nal(2)-D-αMe,pCl-Phe-D-Pal(3)-Ser-Arg-D-Pal(3)-Leu-Bth-Pro-D-AlaNH 2 ;    N-Ac-D-Nal(2)-D-αMe,pCl-Phe-D-Pal(3)-Ser-Tyr-D-Pal(3)-Leu-Bth-Pro-D-AlaNH 2 ;    N-Ac-D-Nal(2)-D-αMe,pCl-Phe-D-Trp-Ser-Arg-D-Trp-Leu-Bth-Pro-D-AlaNH 2 ;    N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Tyr-D-Glu(AA)-Leu-Bth-Pro-D-AlaNH 2 ;    N-Ac-D-Nal(2)-D-pCl-Phe-D-Pal(3)-Ser-Arg-D-Glu(AA)-Leu-Bth-Pro-D-AlaNH 2 ;    N-Ac-D-Nal(2)-D-pCl-Phe-D-Trp-Ser-Arg-D-Glu(AA)-Leu-Bth-Pro-D-AlaNH 2 ;    N-Ac-D-pCl-Phe-D-Phe-D-Phe-Ser-Phe-D-Lys(Nic)-Nle-Bth-Pro-GlyNH 2 ;    N-Ac-Δ 3,4 Pro-D-Nal(2)-D-Pal(3)-Ser-Pal(3)-D-Lys(pyridylacetyl)-Phe-Mpa-D-AlaNH 2 ;    N-Ac-Pro-D-pNO 2 -Phe-D-Trp-Ser-Phe-D-Lys(Nic)-Leu-Ppa-Pro-D-LeuNH 2 ;    N-Ac-D-pF-Phe-D-pF-Phe-D-Trp-Ser-Tyr-D-Tyr-Trp-Bth-Pro-AZaGlyNH 2 ;    N-Ac-D-Nal(1)-Dpg-D-Pal(3)-Ser-Tyr-D-Pal(3)-Nal(2)-Bth-Pro-D-AlaNH 2 ; and    N-Ac-D-Tmp-D-pF-Phe-D-Pal(3)-Ser-Tyr-D-Lys(Nic)-Nal(2)-Bth-Pro-NHEt;    or a pharmaceutically acceptable salt thereof to an animal in need of such a treatment, which composition comprises a therapeutically effective amount of the LHRH analogue or pharmaceutically acceptable salt thereof in intimate admixture with a high molecular weight, water-soluble polysaccharide having a molecular weight greater than about 2000 Daltons.    
     
     
         12 . A pharmaceutical composition of  claim 11  comprising from about 2 to about 8 weight percent LHRH analogue and from about 98 to about 92 weight percent water soluble polysaccharide.  
     
     
         13 . The composition of  claim 11  wherein the water-soluble polysaccharide is dextran.  
     
     
         14 . The composition of  claim 13  wherein the pharmaceutically acceptable salt is the acetate.  
     
     
         15 . A pharmaceutical composition for the systemic administration of the LHRH analogue of  claim 11  to an animal in need of such a treatment, which composition consists essentially of a therapeutically effective amount of the LHRH analogue in intimate admixture with dextran, the admixture being in a powder form, wherein a least 75% of the particles of the powder form have diameters of between about 60 microns and 100 microns.  
     
     
         16 . The composition of  claim 11  wherein the powder form includes an absorption enhancer.  
     
     
         17 . The composition of  claim 16  wherein the absorption enhancer is a bile acid surfactant.  
     
     
         18 . The composition of  claim 16  wherein the absorption enhancer is sodium glycocholate.  
     
     
         19 . A method for the systemic administration of a biologically active polypeptide comprising contacting the nasal passages of an animal in need of treatment with a biologically effective amount of the composition of  claim 11 .  
     
     
         20 . A method of systemic administration of the LHRH analogue of  claim 11  to an animal, which method consists essentially of contacting with the nasal passages of the animal an intimate admixture of a therapeutically effective amount of the LHRH analogue and dextran T70, the admixture being in a powder form, wherein at least 75% of the particles of the powder form have a diameter of between 60 microns and 100 microns.