Therapeutic preparations for inhalation

Abstract

The present invention relates to compositions and methods for pulmonary administration of full-length parathyroid hormone to mammalian hosts for the treatment of osteoporosis. Thus there is provided a therapeutic preparation comprising a human full-length parathyroid hormone, or homologues thereof, in the form of a dry powder suitable for inhalation in which at least 50% of said dry powder consists of (a) particles having a diameter of up to 10 microns; or (b) agglomerates, of such particles.

1 . A dry powder inhaler device containing a preparation consisting of a dry powder comprising (i) a parathyroid hormone (PTH), and (ii) a substance that enhances the absorption of PTH in the lower respiratory tract, wherein at least 50% of (i) and (ii) consists of primary particles having a diameter of up to 10 microns, and wherein the substance is selected from the group consisting of a salt of a fatty acid, a bile salt or derivative thereof, a phospholipid, and a cyclodextrin or derivative thereof.  
     
     
         2 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 1 .  
     
     
         3 . The dry powder inhaler device of  claim 1 , wherein the dry powder further comprises a pharmaceutically acceptable carrier.  
     
     
         4 . The dry powder inhaler device of  claim 3 , characterized in that said carrier consists essentially of particles having a diameter of up to 10 microns such that at least 50% of said dry powder consists of, said primary particles being optionally agglomerated primary particles having a diameter of up to 10 microns.  
     
     
         5 . The dry powder inhaler device of  claim 4 , in which at least 50% of the dry powder consists of primary particles having a diameter of between 1 and 6 microns, said primary particles being optionally agglomerated.  
     
     
         6 . The dry powder inhaler device of  claim 3 , characterized in that said carrier consists essentially of coarse particles, such that an ordered mixture may be formed between said active compounds and the carrier.  
     
     
         7 . The dry powder inhaler device of  claim 1 , in which at least 50% of the total mass of parathyroid hormone in the dry powder consists of primary particles having a diameter of between 1 and 6 microns.  
     
     
         8 . The dry powder inhaler device of  claim 7 , characterized in that the parathyroid hormone is a human parathyroid hormone which comprises at least amino acids 1 to 34 of SEQ ID NO: 1.  
     
     
         9 . The dry powder inhaler device of  claim 8 , characterized in that the parathyroid hormone is a human parathyroid hormone which comprises amino acids 1-84 of SEQ ID NO: 1.  
     
     
         10 . The dry powder inhaler device of  claim 3 , characterized in that the carrier is selected from mono-, di-, and polysaccharides, sugar alcohols and polyols.  
     
     
         11 . The dry powder inhaler device of  claim 3 , characterized in that the carrier is lactose.  
     
     
         12 . The dry powder inhaler device of  claim 3 , characterized in that the parathyroid hormone is a human parathyroid hormone which comprises at least amino acids 1 to 34 of SEQ ID NO:1.  
     
     
         13 . The dry powder inhaler device of  claim 4 , characterized in that the parathyroid hormone is a human parathyroid hormone which comprises at least amino acids 1 to 34 of SEQ ID NO: 1.  
     
     
         14 . The dry powder inhaler device of  claim 5 , characterized in that the parathyroid hormone is a human parathyroid hormone which comprises at least amino acids 1 to 34 of SEQ ID NO: 1.  
     
     
         15 . The dry powder inhaler device of  claim 6 , characterized in that the parathyroid hormone is a human parathyroid hormone which comprises at least amino acids 1 to 34 of SEQ ID NO: 1.  
     
     
         16 . The dry powder inhaler device of  claim 7 , characterized in that the parathyroid hormone is a human parathyroid hormone which comprises at least amino acids 1 to 34 of SEQ ID NO: 1.  
     
     
         17 . The dry powder inhaler device of  claim 4 , characterized in that the parathyroid hormone is a human parathyroid hormone which comprises at least amino acids 1 to 84 of SEQ ID NO: 1.  
     
     
         18 . The dry powder inhaler device of  claim 5 , characterized in that the parathyroid hormone is a human parathyroid hormone which comprises at least amino acids 1 to 84 of SEQ ID NO: 1.  
     
     
         19 . The dry powder inhaler device of  claim 6 , characterized in that the parathyroid hormone is a human parathyroid hormone which comprises at least amino acids 1 to 84 of SEQ ID NO: 1.  
     
     
         20 . The dry powder inhaler device of  claim 7 , characterized in that the parathyroid hormone is a human parathyroid hormone which comprises at least amino acids 1 to 84 of SEQ ID NO: 1.  
     
     
         21 . The dry powder inhaler device of  claim 1 , wherein the substance is a salt of a fatty acid.  
     
     
         22 . The dry powder inhaler device of  claim 21 , wherein the salt of a fatty acid is sodium caprate.  
     
     
         23 . The dry powder inhaler device of  claim 1 , wherein the substance is a bile salt.  
     
     
         24 . The dry powder inhaler device of  claim 23 , wherein the bile salt is sodium taurocholate.  
     
     
         25 . The dry powder inhaler device of  claim 1 , wherein the substance is a phospholipid.  
     
     
         26 . The dry powder inhaler device of  claim 1 , wherein the substance is a cyclodextrin.  
     
     
         27 . The dry powder inhaler device of  claim 1 , wherein the primary particles are agglomerated.  
     
     
         28 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 3 .  
     
     
         29 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 4 .  
     
     
         30 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 5 .  
     
     
         31 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 6 .  
     
     
         32 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 7 .  
     
     
         33 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 8 .  
     
     
         34 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 9 .  
     
     
         35 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 10 .  
     
     
         36 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 11 .  
     
     
         37 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 12 .  
     
     
         38 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 13 .  
     
     
         39 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 14 .  
     
     
         40 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 15 .  
     
     
         41 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 16 .  
     
     
         42 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 17 .  
     
     
         43 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 18 .  
     
     
         44 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry power from the dry powder inhaler device of  claim 19 .  
     
     
         45 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 20 .  
     
     
         46 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 21 .  
     
     
         47 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 22 .  
     
     
         48 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 23 .  
     
     
         49 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 24 .  
     
     
         50 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 25 .  
     
     
         51 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 26 .  
     
     
         52 . A method of delivering parathyroid hormone to a mammal, the method comprising causing the mammal to inhale the dry powder from the dry powder inhaler device of  claim 27 .  
     
     
         53 . A dry powder inhaler device containing a preparation consisting of a dry powder comprising (i) a full-length parathyroid hormone (PTH), and (ii) a substance which enhances the absorption of PTH in the lower respiratory tract, wherein at least 50% of (i) and (ii) consists of primary particles having a diameter of up to 10 microns.  
     
     
         54 . The dry powder inhaler device of  claim 53 , wherein the dry powder further comprises a pharmaceutically acceptable carrier.  
     
     
         55 . The dry powder inhaler device of  claim 54 , characterized in that said carrier consists essentially of particles having a diameter of up to 10 microns such that at least 50% of said dry powder consists of primary particles having a diameter of up to 10 microns said primary particles being optionally agglomerated.  
     
     
         56 . The dry powder inhaler device of  claim 55 , in which at least 50% of the dry powder consists essentially of primary particles having a diameter of between 1 and 6 microns said primary particles being optionally agglomerated.  
     
     
         57 . The dry powder inhaler device of  claim 54 , characterized in that said carrier consists essentially of coarse particles, such that an ordered mixture may be formed between said active compounds and the carrier.  
     
     
         58 . The dry powder inhaler device of  claim 53 , in which at least 50% of the total mass of parathyroid hormone in the dry powder consists of primary particles having a diameter of between 1 and 6 microns.  
     
     
         59 . The dry powder inhaler device of  claim 53 , characterized in that the full-length parathyroid hormone is a human full-length parathyroid hormone.  
     
     
         60 . The dry powder inhaler device of  claim 54 , characterized in that the carrier is selected from mono-, di-, and polysaccharides, sugar alcohols, and polyols.  
     
     
         61 . The dry powder inhaler device of  claim 54 , characterized in that the carrier is lactose.  
     
     
         62 . The dry powder inhaler device of  claim 53 , wherein the substance is a salt of a fatty acid.  
     
     
         63 . The dry powder inhaler device of  claim 62 , wherein the salt of a fatty acid is sodium caprate.  
     
     
         64 . The dry powder inhaler device of  claim 53 , wherein the substance is a bile salt.  
     
     
         65 . The dry powder inhaler device of  claim 64 , wherein the bile salt is sodium taurocholate.  
     
     
         66 . The dry powder inhaler device of  claim 53 , wherein the substance is a phospholipid.  
     
     
         67 . The dry powder inhaler device of  claim 53 , wherein the substance is a cyclodextrin.  
     
     
         68 . The dry powder inhaler device of  claim 53 , wherein the primary particles are agglomerated.