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.

We claim: 
     
         1 . A method for desensitizing patients to an allergen by delivering one or more antigens through hollow microneedles by application of high pressure. 
     
     
         2 . The method of  claim 1  wherein the antigen is one or a combination of peanut flour,  Arachis hypogaea  1 (Ara h1),  Arachis hypogaea  2 (Ara h2), Fel D1, Fel D2, Fel D3, Fel D4, cat IgA, DER p1, DER p2, Bet v1, Bet v2, PLA2, bee sting allergen, wasp allergen, cockroach calyx, penicillin, enteroviruses, sulfonamides, salicylates, albumen, pollen, house dust endotoxin or their derivatives. 
     
     
         3 . A method for desensitizing patients to an allergen by delivering one or more antigens in suspension or solution by application of high pressure. 
     
     
         4 . The method of  claim 1  wherein the allergen is delivered as a population of microparticles wherein at least seventy, more preferably eighty, and most preferably ninety percent of the microparticles are one to ten microns in equivalent circle diameter. 
     
     
         5 . The method of  claim 1  wherein the allergen is delivered as a population of microparticles having a mean equivalent circle diameter in the range of one to ten microns, more preferably two to nine microns, most preferably three to six microns. 
     
     
         6 . The method of  claim 1  wherein the microparticles release less than twenty five percent, more preferably less than fifteen percent, and most preferably less than ten percent of the antigen within forty eight hours. 
     
     
         7 . The method of  claim 1  comprising delivering one or more microencapsulated antigens in solution intradermally through hollow microneedles by application of high pressure. 
     
     
         8 . The method of  claim 1  comprising delivering one or more microencapsulated antigens in suspension intradermally through hollow microneedles by application of high pressure. 
     
     
         9 . The method of  claim 1  wherein the antigen is microencapsulated in a polymer matrix or shell, wherein the polymer is water soluble, pH sensitive, biodegradable, bioadhesive, or cleaved by an enzyme or enzymes found predominantly within the lysosomes of macrophages or dendritic cells. 
     
     
         10 . The method of  claim 9  wherein the polymer is one or a combination of polyamino acids. 
     
     
         11 . A method for desensitizing patients to an allergen by delivering one or more antigens in biodegradable or water soluble polymer barbs delivered intradermally via a solid microneedle array, wherein the antigen-containing barbs are attached to a backing and supporting microstructure. 
     
     
         12 . The method of  claim 11 , wherein at least approximately seventy percent, more preferably eighty percent, most preferably ninety percent or the antigen-containing barbs remain in the dermis after the backing and supporting microstructures have been removed. 
     
     
         13 . The method of  claim 11  wherein at least seventy percent, more preferably eighty percent, most preferably ninety percent of the population of barbs that remain in the dermis after application have an equivalent circle diameter between one and ten microns, more preferably between two and nine microns, and most preferably between three and six microns. 
     
     
         14 . Method for desensitizing patients to an allergen by delivering one or more antigens as a dry powder or in suspension orally within an enterically coated capsule or tablet. 
     
     
         15 . Method for desensitizing patients to an allergen by exposing macrophages acquired from a patient in whole or fractionated blood to antigen microparticles then reintroduced into the patient by injection or intravenous infusion. 
     
     
         16 . Method for desensitizing patients to an allergen by exposing macrophages acquired from a patient in whole or fractionated blood to microencapsulated antigen microparticles then reintroduced into the patient by injection or intravenous infusion. 
     
     
         17 . The method of any one of  claims 1  to  16  wherein a net charge altering agent is added to promote macrophage engulfment. 
     
     
         18 . The method of  claim 17  wherein the net charge altering agent is one or a combination of charged amino acids. 
     
     
         19 . A method for desensitizing patients to an allergen by delivering the antigen to the lymphatic system of any of any one of  claims 1  to  18  comprising administering the allergen once every fourteen days for a period of 168 days, more preferably 84 days, and most preferably 42 days, or once monthly for a period of three to twelve months, more preferably three to six months, and most preferably three months. 
     
     
         20 . A method for desensitizing patients to an allergen by delivering the antigen to the lymphatic system of any one of  claims 1  to  19  comprising administering the allergen in a single dose or using a controlled release formulation that achieves the therapeutic benefit of the multiple dose scheme. 
     
     
         21 . A method for desensitizing patients to an allergen by delivering the antigen to the lymphatic system by the method of any one of  claims 1  to  20  wherein there is a more than a three fold increase in immunoglobulin G levels without increasing immunoglobulin E levels by more than two fold. 
     
     
         22 . A composition for use in the any of the methods of  claims 1  to  21 .