Methods for effectively and rapidly desensitizing allergic patients

Abstract

Methods and compositions for delivering antigens to the lymphatic system in doses that desensitize patients to future exposure to antigens have been developed. Rapid desensitization is achieved by introducing small quantities of antigen into the lymphatic system. In preferred embodiments, the compositions are administered to yield therapeutically effective levels of antigen within the lymph, where macrophages reside in the greatest concentration, by intradermal administration, using for example, microneedles or microparticles, oral administration, using for example, enteric coated capsules or tablets, or autologous transfusion. In some embodiments, the methods and compositions for delivering antigens orally achieve uptake by the Peyer's patches of the small intestines.

1 - 22 . (canceled) 
     
     
         23 . A method for selective delivery of therapeutically effective levels of one or more antigens to the lymphatic system, said method comprising the step of administering to a patient by intradermal injection of microparticles comprising one or more antigens through hollow microneedles, the microparticles having a mean equivalent circle diameter in a range of one to ten microns and comprising chitosan or a chitosan derivative, that is an enzymatically cleavable polymer that is sensitive to degradation by macrophage lysosomal enzymes, wherein less than twenty-five percent of the one or more antigens is released from the microparticles within forty-eight hours of administration prior to uptake by macrophages in the lymphatic system. 
     
     
         24 . The method of  claim 23 , wherein the antigen is one or a combination of peanut flour allergen,  Arachis hypogaea  (ARA h1),  Arachis hypogaea  2 (Ara h2, Fel D1, Fel D2, Fel D3, Fel D4, DER p1, DER p2, Bet v 1, Bet v2, PLA2, bee sting allergen, wasp allergen, cockroach calyx allergen, penicillin allergen, sulfonamides, pollen allergen or house dust allergen. 
     
     
         25 . The method of  claim 23 , wherein the microparticles are administered in suspension. 
     
     
         26 . The method of  claim 23 , wherein at least seventy percent of the microparticles are between three and six microns in equivalent circle diameter. 
     
     
         27 . The method of  claim 23 , comprising delivering the microparticles through the hollow microneedles by application of high pressure. 
     
     
         28 . The method of  claim 23 , wherein the microparticles release less than ten percent of the one or more antigens within forty-eight hours prior to uptake by macrophages in the lymphatic system. 
     
     
         29 . The method of  claim 23 , wherein the microparticles are comprised of chitosan crosslinked with sodium tripolyphosphate. 
     
     
         30 . The method of  claim 23 , comprising administering the microparticles for a period selected from the group consisting of once every fourteen days for a period of between 42 and 168 days, and once monthly for a period of between three and twelve months. 
     
     
         31 . The method of  claim 23 , wherein there is more than a three-fold increase in immunoglobulin G levels without increasing immunoglobulin E levels by more than two fold in the patient following administration.