US2017367648A1PendingUtilityA1

Methods for determining total body skeletal muscle mass

Assignee: GLAXOSMITHKLINE LLCPriority: Dec 7, 2011Filed: Jul 10, 2017Published: Dec 28, 2017
Est. expiryDec 7, 2031(~5.4 yrs left)· nominal 20-yr term from priority
G01N 30/7233H01J 49/004G01N 33/493A61B 10/007A61B 5/15H01J 49/0036A61B 5/4519A61B 5/4869A61B 5/107G01N 33/70
66
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

The present invention is based on the finding that enrichment of D3-creatinine in a urine sample following; oral administration of a single defined dose of D3-creatine can be used to calculate total-body creatine pool size and total body skeletal muscle mass in a subject. The invention further encompasses methods for detecting creatinine and D3-creatinine in a single sample. The methods of the invention find use, inter alia, in diagnosing disorders related to skeletal muscle mass, and in screening potential therapeutic agents to determine their effects on muscle mass.

Claims

exact text as granted — not AI-modified
1 . A method of determining total body skeletal muscle mass in a subject, comprising:
 (a) orally administering D 3 -creatine to a subject, wherein the D 3 -creatine dilutes in the total body skeletal muscle pool of creatine and reaches isotopic steady-state in the total body skeletal muscle pool of creatine;   (b) obtaining a biological sample comprising creatinine and D 3 -creatinine from the subject, wherein the biological sample is selected from the group consisting of a blood sample, a serum sample, a plasma sample, and a tissue sample;   (c) detecting creatinine and D 3 -creatinine in the biological sample by a method selected from the group consisting of HPLC/MS, HPLC/MS/MS, LCMS, LC/MS/MS, and isotope ratio mass spectrometry (IRMS);   (d) measuring enrichment ratio of D 3 -creatinine in the biological sample at a time t based on the creatinine and D 3 -creatinine detected in (c);   (e) measuring a total amount of urinary D 3 -creatinine from administration of the D 3 -creatine to the time t;   (f) determining total-body creatine pool size in the subject by the formula   
       
         
           
             
               
                 
                   
                     
                       
                         
                           [ 
                           
                             
                               Amount 
                                
                               
                                   
                               
                                
                               of 
                                
                               
                                   
                               
                                
                               
                                 D 
                                 3 
                               
                                
                               
                                 - 
                               
                                
                               creatine 
                                
                               
                                   
                               
                                
                               dosed 
                                
                               
                                   
                               
                                
                               
                                 ( 
                                 g 
                                 ) 
                               
                             
                             - 
                           
                         
                       
                     
                     
                       
                         
                           
                             Total 
                              
                             
                                 
                             
                              
                             amount 
                              
                             
                                 
                             
                              
                             of 
                              
                             
                                 
                             
                              
                             urinary 
                              
                             
                                 
                             
                              
                             
                               D 
                               3 
                             
                              
                             
                               - 
                             
                              
                             creatine 
                              
                             
                                 
                             
                              
                             
                               ( 
                               
                                 o 
                                 - 
                                 t 
                               
                               ) 
                             
                              
                             
                               ( 
                               g 
                               ) 
                             
                           
                           ] 
                         
                       
                     
                   
                   
                     enrichment 
                      
                     
                         
                     
                      
                     ratio 
                      
                     
                         
                     
                      
                     
                       ( 
                       t 
                       ) 
                     
                   
                 
                 = 
                 
                   total 
                    
                   
                     - 
                   
                    
                   body 
                    
                   
                       
                   
                    
                   creatine 
                    
                   
                       
                   
                    
                   pool 
                    
                   
                       
                   
                    
                   size 
                 
               
               ; 
             
           
         
       
       and
 (g) determining total body skeletal muscle mass in the subject based on the formula 
 
       
         
           
             
               
                 Total 
                  
                 
                     
                 
                  
                 body 
                  
                 
                     
                 
                  
                 skeletal 
                  
                 
                     
                 
                  
                 muscle 
                  
                 
                     
                 
                  
                 mass 
               
               = 
               
                 
                   ( 
                   
                     
                       the 
                        
                       
                           
                       
                        
                       total 
                        
                       
                         - 
                       
                        
                       body 
                        
                       
                           
                       
                        
                       creatine 
                        
                       
                           
                       
                        
                       pool 
                        
                       
                           
                       
                        
                       size 
                     
                     
                       creatine 
                        
                       
                           
                       
                        
                       concentration 
                        
                       
                           
                       
                        
                       in 
                        
                       
                           
                       
                        
                       skeletal 
                        
                       
                           
                       
                        
                       muscle 
                     
                   
                   ) 
                 
                 . 
               
             
           
         
       
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the biological sample is a blood sample. 
     
     
         4 . The method of  claim 1 , wherein 5-250 mg D 3 -creatine or a salt or hydrate thereof are administered. 
     
     
         5 . The method of  claim 1 , wherein the D 3 -creatine administered is a hydrate of D 3 -creatine. 
     
     
         6 . The method of  claim 5 , wherein the D 3 -creatine is D 3 -creatine monohydrate. 
     
     
         7 . The method of  claim 1 , wherein the biological sample is obtained at least 24 hours after administration of the D 3 -creatine. 
     
     
         8 . The method of  claim 7 , wherein the biological sample is obtained at least 36 hours after administration of the D 3 -creatine. 
     
     
         9 . The method of  claim 7 , wherein the biological sample is obtained at least 48 hours after administration of the D 3 -creatine. 
     
     
         10 . The method of  claim 7 , wherein the biological sample is obtained at least 60 hours after administration of the D 3 -creatine. 
     
     
         11 . The method of  claim 7 , wherein the biological sample is obtained at least 72 hours after administration of the D 3 -creatine. 
     
     
         12 . The method of  claim 1 , wherein the D 3 -creatine is administered to the subject such that the spillage of D 3 -creatine into the urine is minimized, wherein greater than 99% of the administered D 3 -creatine dilutes in the total body skeletal muscle pool of creatine and reaches isotopic steady-state in the total body skeletal muscle pool of creatine. 
     
     
         13 . The method of  claim 1 , wherein the creatine concentration in skeletal muscle is 4.3 g/kg. 
     
     
         14 . The method of  claim 1 , wherein the biological sample is selected from the group consisting of a blood sample, a serum sample, and a plasma sample

Join the waitlist — get patent alerts

Track US2017367648A1 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.