Particulate agents

Abstract

A novel means of pharmaceutical delivery for therapy of prophylaxis or to assist surgical or diagnostic operations on the living body is provided by neuronal endocytosis and axonal transport following pharmaceutical administration into vascularized, peripherally innervated tissue, e.g., intramuscular injections of a nerve adhesion molecule in coupled particle comprising a physiologically active substance or a diagnostic marker.

1 . A method of treatment of the living human or non-human body to effect a desired therapeutic or prophylactic treatment or assist diagnostic investigation or surgical treatment thereof, said method comprising administering into a vascularized peripherally innervated tissue site or into other tissue sites innervated by a spinal root a particulate pharmaceutical agent comprising a nerve adhesion moiety serving to promote neuronal endocytosis of said agent and a physiologically active or diagnostic marker moiety capable of axonal transport from said tissue site.  
     
     
         2 . The use of a particulate pharmaceutical agent comprising a nerve adhesion moiety serving to promote neuronal endocytosis of said agent and a physiologically active or diagnostic marker moiety capable of axonal transport following neuronal endocytosis of said agent for the preparation of a therapeutic, prophylactic or diagnostic composition for use on administration into a vascularized peripherally innervated tissue site or into other tissue sites innervated by a spinal root in a method of treatment of the living human or non-human body to effect a desired therapeutic or prophylactic treatment or assist diagnostic investigation or surgical treatment thereof.  
     
     
         3 . A pharmaceutical agent comprising a nerve adhesion molecule coupled to an optionally-coated, particulate, physiologically active or diagnostically marked substance, with the provisos that for diagnostically marked substances the substance is a metal oxide, metal sulphide or alloy.  
     
     
         4 . A composition as claimed in  claim 3  wherein said particles have a mean particle size of 10-50 nm.  
     
     
         5 . A composition as claimed-in either of claims  3  and  4  wherein said particles have a spinel structure.  
     
     
         6 . A composition as claimed in any one of  claims 3  to  5  wherein said particles are superparamagnetic.  
     
     
         7 . A composition as claimed in many one of  claims 3  to  6  wherein said particles incorporate radionuclides.  
     
     
         8 . A physiologically tolerable particulate metal oxide, metal sulphide or alloy with incorporated therein a positron emitter radionuclide.  
     
     
         9 . A particulate metal oxide, metal sulphide or alloy as claimed in  claim 8  further containing atoms of an element having a higher positron affinity than iron.  
     
     
         10 . A particulate metal oxide, metal sulphide or alloy as claimed in  claim 9  containing lithium or zinc.  
     
     
         11 . A particulate metal oxide as claimed in any one of  claims 8  to  10  having a spinel or garnet structure.  
     
     
         12 . A particulate metal oxide as claimed in  claim 11  being a ferrite.  
     
     
         13 . A particulate metal oxide, metal sulphide or alloy as claimed in any one of  claims 8  to  12  containing Mn 52 , Fe 52  or Sc 43 .  
     
     
         14 . A particulate metal oxide as claimed in any one of  claims 8  to  13 ,for use in medicine.  
     
     
         15 . A physiologically tolerable particulate garnet or spinel with incorporated therein atoms of scandium, of a radioactive yttrium isotope of a sixth period metal of a high MR receptivity nuclide or of an element which on particle degradation has a desired therapeutic or prophylactic activity.  
     
     
         16 . A particulate spinel or garnet as claimed in  claim 15  containing atoms of scandium.  
     
     
         17 . A particulate spinel or garnet as claimed in either of claims  15  and  16  containing atoms of a lanthanide.  
     
     
         18 . A particulate spinel or garnet as claimed in any one of  claims 15  to  16  having a mean particle size of less than 100 nm and containing on average at least 100 atoms of scandium or a sixth period element per particle.  
     
     
         19 . A particulate spinel or garnet as claimed in any one of  claims 15  to  18  for use in medicine.  
     
     
         20 . A process for the preparation of a particulate pharmaceutical agent as claimed in  claim 8  which process comprises conjugating a NAM to an optionally coated particulate physiologically active or diagnostically marked substance.  
     
     
         21 . A process as claimed in  claim 20  wherein dextran coated particles are conjugated to a NAM.  
     
     
         22 . A process as claimed in  claim 21  wherein said dextran coated particles are subjected to periodation prior to conjugation to the NAM.  
     
     
         23 . A process as claimed in any one of  claims 20  to  22  wherein the NAM is WGA.  
     
     
         24 . A process as claimed in any one of  claims 20  to  23  wherein the NAM-conjugated particles are subjected to repeated size separations and at least one affinity separation.  
     
     
         25 . A process for the preparation of a physiologically tolerable marked metal oxide, metal sulphide or alloy as claimed in  claim 15  which comprises precipitating a said metal oxide or sulphide from a solution containing a positron emitter nuclide and if desired reducing the precipitate.  
     
     
         26 . A process for the preparation of a modified spinel or garnet particle as claimed in  claim 15  which process comprises precipitating di and trivalent metal ions of ionic radii such as to permit crystals of spinel or garnet structure to form, said precipitation being from a solution containing scandium, a radioactive yttrium isotope, a sixth period metal, a high MR receptivity nuclide or an element having a desired therapeutic or prophylactic activity.  
     
     
         27 . A process as claimed in either of claims  25  and  26  wherein the element to be included in the precipitated particles is provided in seed crystals which become incorporated in the precipitated particles.  
     
     
         28 . A radiotherapeutic composition comprising a cell adhesion moiety-coupled radionuclide and a tissue glue.  
     
     
         29 . A method of producing a physiologically tolerable particulate metal oxide, said method comprising precipitating said oxide from a biologically tolerable, physiological pH buffered solution, optionally containing a coating agent whereby coated particles are formed.