Kits for dhea and dhea-sulfate for the treatment of chronic obstructive pulmonary disease

Abstract

Kits for treating or preventing chronic obstructive pulmonary disease (COPD) by using as active agent a non-glucorticoid steroid, analogue thereof, such as dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S), or their salts, in an amount effective for preventing or treating COPD.

1 . A delivery kit for the treatment of COPD comprising, in separate containers, an active agent selected from a non-glucocorticoid steroid having the chemical formula: 
     
       
         
         
             
             
         
       
       wherein the broken line represents a single or a double bond; R is hydrogen or a halogen; the H at position 5 is present in the alpha or beta configuration or the compound of chemical formula I comprises a racemic mixture of both configurations; 
       and R 1  is hydrogen or SO 2 OM, wherein M is selected from the group consisting of H, Na, sulfatide 
     
     
       
         
         
             
             
         
       
       wherein R 2  and R 3 , which may be the same or different, are straight or branched (C 1 -C 14 ) alkyl or glucuronide 
     
     
       
         
         
             
             
         
       
       or a non-glucocorticoid steroid of the chemical formula 
     
     
       
         
         
             
             
         
       
       wherein R1, R2, R3, R4, R5, R7, R8, R9, R10, R12, R13, R14 and R19 are independently H, OR, halogen, (C 1 -C 10 ) alkyl or (C 1 -C 10 ) alkoxy, R5 and R11 are independently OH, SH, H, halogen, pharmaceutically acceptable ester, pharmaceutically acceptable thioester, pharmaceutically acceptable ether, pharmaceutically acceptable thioether, pharmaceutically acceptable inorganic esters, pharmaceutically acceptable monosaccharide, disaccharide or oligosaccharide, spirooxirane, spirothirane, —OSO2R20, —OPOR20R21 or (C 1 -C 10 ) alky, R5 and R6 taken together are ═O, R10 and R11 taken together are ═O; R15 is (1) H, halogen, (C 1 -C 10 ) alkyl, or (C 1 -C 10 ) alkoxy when R16 is —C(O)OR22, (2) H, halogen, OH or (C 1 -C 10 ) alkyl when R16 is halogen, OH or (C 1 -C 10 ) alkyl, (3) H, halogen, (C 1 -C 10 ) alkyl, (C 1 -C 10 ) alkenyl, (C 1 -C 10 ) alkynyl, formyl, (C 1 -C 10 ) alkanoyl or epoxy when R16 is OH, (4) OR, SH, H, halogen, pharmaceutically acceptable ester, pharmaceutically acceptable thioester, pharmaceutically acceptable ether, pharmaceutically acceptable thioether, pharmaceutically acceptable inorganic esters, pharmaceutically acceptable monosaccharide, disaccharide or oligosaccharide, spirooxirane, spirothirane, —OSO2R20 or —OPOR20R21 when R16 is H, or R15 and R16 taken together are ═O; R17 and R18 are independently (1) H, —OH, halogen, (C 1 -C 10 ) alkyl or —(C 1 -C 10 ) alkoxy when R6 is H, OR, halogen, (C 1 -C 10 ) alkyl or —C(O)OR22, (2) H, ((C 1 -C 10 ) alkylamino, ((C 1 -C 10 ) alkyl)n amino-(C 1 -C 10 ) alkyl, (C 1 -C 10 ) alkoxy, hydroxy-(C 1 -C 10 ) alkyl, (C 1 -C 10 ) alkoxy-(C 1 -C 10 ) alkyl, (halogen)m (C 1 -C 10 ) alkyl, (C 1 -C 10 ) alkanoyl, formyl, (C 1 -C 10 ) carbalkoxy or (C 1 -C 10 ) alkanoyloxy when R15 and R16 taken together are ═O, (3) R17 and R18 taken together are ═O; (4) R17 or R18 taken together with the carbon to which they are attached form a 3-6 member ring containing 0 or 1 oxygen atom; or (5) R15 and R17 taken together with the carbons to which they are attached form an epoxide ring; R20 and R21 are independently OH, pharmaceutically acceptable ester or pharmaceutically acceptable ether; R22 is H, (halogen) m  (C 1 -C 10 ) alkyl or (C 1 -C 10 ) alkyl; n is 0, 1 or 2; and m is 1, 2 or 3; or pharmaceutically or veterinarily acceptable salts thereof; and 
       a delivery device. 
     
   
   
       2 . The delivery kit of  claim 1 , wherein the active agents is provided as an inhalable, respirable, intrapulmonary or nasal formulation, and the delivery device comprises an inhaler provided with an aerosol or spray generating means that delivers particles about 0.05 to about 10 micron in size or about 10 to about 100 micron in size. 
   
   
       3 . The delivery kit of  claim 2 , wherein the delivery device delivers individual pre-metered doses of the formulation. 
   
   
       4 . The delivery kit of  claim 1 , wherein the delivery device comprises an inhaler. 
   
   
       5 . The delivery kit of  claim 4 , wherein the inhaler comprises a nebulizer or insufflator. 
   
   
       6 . The delivery kit of  claim 1 , wherein the delivery device comprises a compression inhaler, and the active agent is provided as an inhalable or respirable formulation comprising a suspension or solution in an aqueous or non-aqueous liquid or an oil-in-water or water-in-oil emulsion. 
   
   
       7 . The delivery kit of  claim 1 , wherein the active agent is provided as a formulation in a pierceable or openable capsule or cartridge. 
   
   
       8 . The delivery kit of  claim 1 , wherein the active agent is provided in a single-dose or multi-dose form. 
   
   
       9 . The delivery kit of  claim 8 , wherein the active agent is provided in sealed ampoules or vials. 
   
   
       10 . The delivery kit of  claim 8 , wherein the active agent is provided freeze-dried or lyophilized. 
   
   
       11 . The delivery kit of  claim 6 , wherein the inhaler comprises an ultrasonic nebulizer. 
   
   
       12 . The delivery kit of  claim 11 , wherein the formulation comprises an aqueous suspension