Patent RU-2716257-C1 (RU)
Title: Active component, pharmaceutical composition and drug preparation for hiv and aids therapy
Inventor: IVASHCHENKO ALEKSANDR VASILEVICH
IPC: A61K31/18
Filed: 2019-04-30
Granted: 2020-03-11
Abstract: FIELD: chemistry. 
     SUBSTANCE: invention relates to micronized monoclinic symmetry crystals (MMSC) with average particle diameter of ≤130 mcm sodium {[4-({[4-bromo-3-(3-chloro-5-cyanophenoxy)-2-fluorophenyl]acetyl}amino)-3-chlorophenyl]-sulphonyl}(propanoyl)azanide - of formula Ib, sodium {[4-({[4-bromo-3-(3-chloro-5-cyanophenoxy)-2-fluorophenyl]acetyl}amino)-3-chlorophenyl]-sulphonyl}(propanoyl)azanide of formula Ib. Crystals are an active component of a pharmaceutical composition and a medicinal agent for use in therapy of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS). Micronized crystals of the compound of formula Ib 
     
       
     
     have the following crystal characteristics: 
     
       
         
               
               
             
                 crystalline form 
                 monoclinic 
               
                 Z 
                 1h 
               
                 spatial group 
                 P21/c 
               
                 a 
                 15.0367(4)Å 
               
                 b 
                 25.2592(6)Å 
               
                 c 
                 6.89727(19)Å 
               
                 α 
                 - 
               
                 β 
                 91.216(2)° 
               
                 γ 
                   
               
                 V, Ά 
                 2623.79(12) Å 3   
               
           
              
              
              
              
              
              
              
              
              
              
             
          
         
       
     
     and indicators powder X having interplanar spacings (D) and relative intensities (I rel  = I/I o  × 100) diffraction peaks of the monoclinic phase of the sample in angle region 2θ° 6°–30°: 
     
       
         
               
               
             
                 (D) 
                 I/I o ×100 
               
                 7.6 
                 29 
               
                 7.2 
                 100 
               
                 6.5 
                 37 
               
                 4.7 
                 67 
               
                 4.1 
                 70 
               
                 3.9 
                 85 
               
           
              
              
              
              
              
              
              
             
          
         
       
     
     MMSC with said monoclinic crystal structure have DSC values within 244–253.5 °C with peak of 250 °C. Average particle diameter is from 10 to 130 mcm. Pharmaceutical composition has a solid form and additionally contains as excipients at least lactose monohydrate, sodium croscarmellose, povidone and magnesium stearate. Medicinal preparation is used in the form of an oral form. 
     EFFECT: comparative data on use of micronized and non-micronized particles (Ib and Ia, respectively) show that micronized particles increase exposure time of compound Ib in blood plasma. 
     17 cl, 4 dwg, 2 tbl, 8 ex