Dual-chamber carpule with attachment

Abstract

The invention relates to a dual-chamber carpule comprising a cylinder comprising a bypass, a central plug and an end plug, and an attachment; the invention further relates to a method for producing and filling said dual-chamber carpule.

1 . A two-chamber carpule comprising
 a) a cylinder containing
 an end plug, which is positioned at the proximal end of the cylinder, 
 optionally a stop ( 13 ) at the proximal end ( 9 ), 
 an intermediate plug ( 6 ), 
 a bypass ( 3 ), 
 a distal end ( 8 ) for connecting to the attachment, 
   b) an attachment comprising
 a closure with a distal opening suitable for piercing with an application needle and optionally a needle holder, 
 one or more sealing elements for sealing the distal end of the closure and for sealing the connection between the closure and the cylinder. 
   
     
     
         2 . The two-chamber carpule as claimed in  claim 1 , the closure being of a one-piece configuration 
     
     
         3 . The two-chamber carpule as claimed in  claim 2 , the closure being formed by an integrated closure cap with or without a head part. 
     
     
         4 . The two-chamber carpule as claimed in  claim 2 , the attachment comprising a one-piece, integrated closure cap ( 22 ) with a distal opening, a sealing element for sealing the distal end of the integrated closure cap ( 22 ) and optionally (with preference) a further sealing element ( 7 ) for sealing the connection between the integrated closure ( 22 ) and the cylinder ( 1 ). 
     
     
         5 . The two-chamber carpule as claimed in  claim 2 , the attachment comprising a one-piece closure element ( 16 ) with a distal opening, a sealing element ( 15 ) for sealing the distal end of the closure element ( 16 ) and for sealing the connection between the closure element ( 16 ) and the cylinder ( 1 ). 
     
     
         6 . The two-chamber carpule as claimed in  claim 1 , the closure being of a two-piece configuration. 
     
     
         7 . The two-chamber carpule as claimed in  claim 6 , the attachment comprising a head ( 2 ) and a closure cap ( 5 ) with a distal opening suitable for piercing with an application needle and optionally a needle holder, a sealing element for sealing the connection between the head ( 2 ) and the closure cap ( 5 ) and optionally a further sealing element ( 7 ) for sealing the connection between the head ( 2 ) and the cylinder ( 1 ). 
     
     
         8 . The two-chamber carpule as claimed in  claim 1 , the closure being of a three-piece configuration. 
     
     
         9 . The two-chamber carpule as claimed in  claim 8 , the attachment comprising a head ( 2 ), a head holder ( 19 ) and a closure cap ( 5 ) with a distal opening suitable for piercing with an application needle and optionally a needle holder, a sealing element for sealing the connection between the head ( 2 ) and the closure cap ( 5 ) and optionally a further sealing element ( 7 ) for sealing the connection between the head ( 2 ) and the cylinder ( 1 ). 
     
     
         10 . The two-chamber carpule as claimed in  claim 6 , the proximal end of the head ( 2 ) or the distal end of the cylinder ( 1 ) having an axial groove ( 11 ) on the inner side of the receiving component. 
     
     
         11 . The two-chamber carpule as claimed in  claim 6 , the proximal end of the head ( 2 ) or the distal end of the cylinder ( 1 ) having an axial groove ( 11 ) on the inner side of the receiving component, and the proximal end of the cylinder ( 1 ) having a stop ( 13 ). 
     
     
         12 . The two-chamber carpule as claimed in  claim 1 , the medicaments to the administered being a peptide for the treatment of Diabetes mellitus or complications of Diabetes mellitus. 
     
     
         13 . The two-chamber carpule as claimed in  claim 12 , the peptide being exendin-4(1-39) or a peptide selected from the group comprising
 H-(Lys) 4 -des Pro 36 , des Pro 37  exendin-4(1-39)-NH 2 ,   H-(Lys) 5 -des Pro 36 , des Pro 37  exendin-4(1-39)-NH 2 ,   des Pro 36  [Asp 28 ] exendin-4(1-39),   des Pro 36  [IsoAsp 28 ] exendin-4(1-39),   des Pro 36  [Met(O) 14 , Asp 28 ] exendin-4(1-39),   des Pro 36  [Met(O) 14 , IsoAsp 28 ] exendin-4(1-39),   des Pro 36  [Trp(O 2 ) 25 , Asp 28 ] exendin-4(1-39),   des Pro 36  [Trp(O 2 ) 25 , IsoAsp 28 ] exendin-4(1-39),   des Pro 36  [Met(O) 14  Trp(O 2 ) 25 , Asp 28 ] exendin-4(1-39),   des Pro 36  [Met(O) 14  Trp(O 2 ) 25 , IsoAsp 28 ] exendin-4(1-39),   H-(Lys) 6 -des Pro 36  [Asp 28 ] exendin-4(1-39)-Lys 6 -NH 2 ,   des Asp 28  Pro 36 , Pro 37 , Pro38exendin-4(1-39)-NH 2 ,   H-(Lys) 6 -des Pro 36 , Pro 38  [Asp 28 ] exendin-4(1-39)-NH 2 ,   H-Asn-(Glu) 5 des Pro 36 , Pro 37 , Pro 38  [Asp 28 ] exendin-4(1-39)-NH 2 ,   des Pro 36 , Pro 37 , Pro 38  [Asp 28 ] exendin-4(1-39)-(Lys) 6 -NH 2 ,   H-(Lys) 6 -des Pro 36 , Pro 37 , Pro 38  [Asp 28 ] exendin-4(1-39)-(Lys) 6 -NH 2 ,   H-Asn-(Glu) 5 -des Pro 36 , Pro 37 , Pro 38  [Asp 28 ] exendin-4(1-39)-(Lys) 6 -NH 2 ,   H-(Lys) 6 -des Pro 36  [Trp(O 2 ) 25 , Asp 28 ] exendin-4(1-39)-Lys 6 -NH 2 ,   H-des Asp 28  Pro 36 , Pro 37 , Pro 38  [Trp(O 2 ) 25 ] exendin-4(1-39)-NH 2 ,   H-(Lys) 6 -des Pro 36 , Pro 37 , Pro 38  [Trp(O 2 ) 25 , Asp 28 ] exendin-4(1-39)-NH 2 ,   H-Asn-(Glu) 5 -des Pro 36 , Pro 37 , Pro 38  [Trp(O 2 ) 25 , Asp 28 ] exendin-4(1-39)-NH 2 ,   des Pro 36 , Pro 37 , Pro 38  [Trp(O 2 ) 25 , Asp 28 ] exendin-4(1-39)-(Lys) 6 -NH 2 ,   H-(Lys) 6 -des Pro 36 , Pro 37 , Pro 38  [Trp(O 2 ) 25 , Asp 28 ] exendin-4(1-39)-(Lys) 6 -NH 2 ,   H-Asn-(Glu) 5 -des Pro 36 , Pro 37 , Pro 38  [Trp(O 2 ) 25 , Asp 28 ] exendin-4(1-39)-(Lys) 6 -NH 2 ,   H-(Lys) 6 -des Pro 36  [Met(O) 14 , Asp 28 ] exendin-4(1-39)-Lys 6 -NH 2 ,   des Met(O) 14  Asp 28  Pro 36 , Pro 37 , Pro 38  exendin-4(1-39)-NH 2 ,   H-(Lys) 6 -desPro 36 , Pro 37 , Pro 38  [Met(O) 14 , Asp 28 ] exendin-4(1-39)-NH 2 ,   H-Asn-(Glu) 5 -des Pro 36 , Pro 37 , Pro 38  [Met(O) 14 , Asp 28 ] exendin-4(1-39)-NH 2 ,   des Pro 36 , Pro 37 , Pro 38  [Met(O) 14 , Asp 28 ] exendin-4(1-39)-(Lys) 6 -NH 2 ,   H-(Lys) 6 -des Pro 36 , Pro 37 , Pro 38  [Met(O) 14 , Asp 28 ] exendin-4(1-39)-(Lys) 6 -NH 2 ,   H-Asn-(Glu) 5  des Pro 36 , Pro 37 , Pro 38  [Met(O) 14 , Asp 28 ] exendin-4(1-39)-(Lys) 6 -NH 2 ,   H-Lys 6 -des Pro 36  [Met(O) 14 , Trp(O 2 ) 25 , Asp 28 ] exendin-4(1-39)-Lys 6 -NH 2 ,   H-des Asp 28  Pro 36 , Pro 37 , Pro 38  [Met(O) 14 , Trp(O 2 ) 25 ] exendin-4(1-39)-NH 2 ,   H-(Lys) 6 -des Pro 36 , Pro 37 , Pro 38  [Met(O) 14 , Asp 28 ] exendin-4(1-39)-NH 2 ,   H-Asn-(Glu) 5 -des Pro 36 , Pro 37 , Pro 38  [Met(O) 14 , Trp(O 2 ) 25 , Asp 28 ] exendin-4(1-39)-NH 2 ,   des Pro 36 , Pro 37 , Pro 38  [Met(O) 14 , Trp(O 2 ) 25 , Asp 28 ] exendin-4(1-39)-(Lys) 6 -NH 2 ,   H-(Lys) 6 -des Pro 36 , Pro 37 , Pro 38  [Met(O) 14 , Trp(O 2 ) 25 , Asp 28 ] exendin-4(S1-39)-(Lys) 6 -NH 2 ,   H-Asn-(Glu) 5 -des Pro 36 , Pro 37 , Pro 38  [Met(O) 14 , Trp(O 2 ) 25 , Asp 28 ] exendin-4(1-39)-(Lys) 6 -NH 2 ;   
       or
 des Pro 36  [Asp 28 ] exendin-4(1-39), 
 des Pro 36  [IsoAsp 28 ] exendin-4(1-39), 
 des Pro 36  [Met(O) 14 , Asp 28 ] exendin-4(1-39), 
 des Pro 36  [Met(O) 14 , IsoAsp 28 ] exendin-4(1-39), 
 des Pro 36  [Trp(O 2 ) 25 , Asp 28 ] exendin-4(1-39), 
 des Pro 36  [Trp(O 2 ) 25 , IsoAsp 28 ] exendin-4(1-39), 
 des Pro 36  [Met(O) 14  Trp(O 2 ) 25 , Asp 28 ] exendin-4(1-39), 
 des Pro 36  [Met(O) 14  Trp(O 2 ) 25 , IsoAsp 28 ] exendin-4(1-39), 
 the group -Lys 6 -NH 2  being linked with the C-terminus of the exendin-4 derivative; 
 
       or a pharmaceutically acceptable salt or solvate thereof. 
     
     
         14 . An applicator including a two-chamber carpule as claimed in  claim 1 . 
     
     
         15 . A method for producing and filling a two-chamber carpule as claimed in  claim 1 , wherein
 a) a cylinder containing a bypass is provided with a middle plug between the bypass and the proximal end;   b) the chamber between the middle plug and the proximal end is filled with a liquid component;   c) the chamber containing the liquid component is closed with an end plug;   d) a liquid component, or with preference solid component, is filled into the chamber between the middle plug and the distal end of the cylinder; and   e) the distal end of the cylinder is closed with an attachment.