Apoptosis-mimicking synthetic entities and use thereof in medical treatment

Abstract

Synthetic and semisynthetic bodies having a three-dimensional structure, sized and shaped to resemble apoptotic cells and apoptotic bodies, and having phosphatidyl serine (PS) molecules on the surface thereof, are administered to a patient, to alleviate a variety of disorders such as T-cell mediated disorders (autoimmune conditions). The bodies are believed to trigger an apoptosis-like mechanism in the patient.

1 - 46 . (canceled)  
     
     
         47 . A method for treating an inflammatory disorder comprising administering to a mammalian patient a non-toxic effective inflammatory disorder-treating amount of PS-carrying bodies, wherein progression of the inflammatory disorder is inhibited and/or the symptoms of the disorder are reduced.  
     
     
         48 . The method of  claim 47  wherein the inflammatory disorder is selected from the group consisting of inflammatory allergic reactions, organ and cell transplantation reaction disorders, microbial infections giving rise to inflammatory disorders, oxidative stress and/or ischemia reperfusion injury, ingestion of poisons, exposure to toxic chemicals, radiation damage, exposure to airborne and water-borne irritant substances that cause damaging inflammation, inflammatory disorders of internal organs, and allergic disorders of internal organs.  
     
     
         49 . The method of  claim 48  wherein the inflammatory disorder is an inflammatory or allergic disorder of the kidney, the liver, or the heart.  
     
     
         50 . The method of  claim 48  wherein the amount of PS-carrying bodies administered is from about 500 to about 500,000,000 bodies.  
     
     
         51 . The method of  claim 50  wherein the amount of PS-carrying bodies administered is from about 10,000 to about 10,000,000 bodies.  
     
     
         52 . The method of  claim 50  wherein the amount of PS-carrying bodies administered is from about 200,000 to about 2,000,000 bodies.  
     
     
         53 . The method of  claim 48  wherein the PS-carrying bodies comprise from about greater than 65% PS.  
     
     
         54 . The method of  claim 53  wherein the PS-carrying bodies comprise from about 65% to about 90% PS.  
     
     
         55 . The method of  claim 53  wherein the PS-carrying bodies comprise from about 70% to about 80% PS.  
     
     
         56 . The method of  claim 53  wherein the PS-carrying bodies comprise about 75% PS.  
     
     
         57 . The method of  claim 53  wherein the PS-carrying bodies are liposomes.  
     
     
         58 . The method of  claim 53  wherein said PS-carrying bodies are biocompatible non-liposomal synthetic bodies.  
     
     
         59 . A method for treating an endothelial function disorder comprising administering to a mammalian patient a non-toxic effective endothelial function disorder-treating amount of PS-carrying bodies, wherein progression of the endothelial function disorder is inhibited and/or the symptoms of the disorder are reduced.  
     
     
         60 . The method of  claim 59  wherein the endothelial function disorder is selected from the group consisting of cardiovascular diseases, vasospastic disorders, and damage resulting from ischemia.  
     
     
         61 . The method of  claim 59  wherein the endothelial function disorder is selected from the group consisting of atherosclerosis, peripheral arterial or arterial occlusive disease, congestive heart failure, cerebrovascular disease (stroke), myocardial infarction, angina, and hypertension.  
     
     
         62 . The method of  claim 59  wherein the endothelial function disorder is selected from the group consisting of Raynaud's disease, cardiac syndrome X, and migraine.  
     
     
         63 . The method of  claim 59  wherein the endothelial function disorder is ischemic injury or ischemia-reperfusion injury.  
     
     
         64 . The method of  claim 59  wherein the amount of PS-carrying bodies administered is from about 500 to about 500,000,000 bodies.  
     
     
         65 . The method of  claim 59  wherein the amount of PS-carrying bodies administered is from about 10,000 to about 10,000,000 bodies.  
     
     
         66 . The method of  claim 59  wherein the amount of PS-carrying bodies administered is from about 200,000 to about 2,000,000 bodies.  
     
     
         67 . The method of  claim 59  wherein the PS-carrying bodies comprise from about greater than 65% PS.  
     
     
         68 . The method of  claim 67  wherein the PS-carrying bodies comprise from about 65% to about 90% PS.  
     
     
         69 . The method of  claim 67  wherein the PS-carrying bodies comprise from about 70% to about 80% PS.  
     
     
         70 . The method of  claim 67  wherein the PS-carrying bodies comprise about 75% PS.  
     
     
         71 . The method of  claim 67  wherein the PS-carrying bodies are liposomes.  
     
     
         72 . The method of  claim 67  wherein said PS-carrying bodies are biocompatible non-liposomal synthetic bodies.  
     
     
         73 . A method for treating an immune system disorder characterized by an inappropriate cytokine expression comprising administering to a mammalian patient a non-toxic effective inappropriate cytokine expression-treating amount of PS-carrying bodies, wherein progression of the disorder is inhibited and/or the symptoms of the reduced.  
     
     
         74 . The method of  claim 73  wherein the immune system disorder characterized by an inappropriate cytokine expression is a neurodegenerative disease or a neurological disorder.  
     
     
         75 . The method of  claim 74  wherein the neurodegenerative disease or neurological disorder is selected from the group consisting of Down's syndrome, senile dementia, depression, multiple sclerosis, Huntingtdon's disease, peripheral neuropathies, spinal cord disease, neuropathic joint diseases, chronic inflammatory demyelinating disease, neuropathies including mononeuropathy, polyneuropathy, symmetrical distal sensory neuropathy, neuromuscular junction disorders, myasthenias and amyotrophic lateral sclerosis (ALS).  
     
     
         76 . The method of  claim 74  wherein the neurodegenerative disease is Alzheimer's disease or Parkinson's disease.  
     
     
         77 . The method of  claim 74  wherein the amount of PS-carrying bodies administered is from about 500 to about 500,000,000 bodies.  
     
     
         78 . The method of  claim 74  wherein the amount of PS-carrying bodies administered is from about 10,000 to about 10,000,000 bodies.  
     
     
         79 . The method of  claim 74  wherein the amount of PS-carrying bodies administered is from about 200,000 to about 2,000,000 bodies.  
     
     
         80 . The method of  claim 74  wherein the PS-carrying bodies comprise from about greater than 65% PS.  
     
     
         81 . The method of  claim 80  wherein the PS-carrying bodies comprise from about 65% to about 90% PS.  
     
     
         82 . The method of  claim 80  wherein the PS-carrying bodies comprise from about 70% to about 80% PS.  
     
     
         83 . The method of  claim 80  wherein the PS-carrying bodies comprise about 75% PS.  
     
     
         84 . The method of  claim 74  wherein the PS-carrying bodies are liposomes.  
     
     
         85 . The method of  claim 74  wherein said PS-carrying bodies are biocompatible non-liposomal synthetic bodies.  
     
     
         86 . A pharmaceutical composition comprising a pharmaceutical carrier and biocompatible non-liposomal synthetic bodies for administration to a mammalian patient wherein the non-liposomal biocompatible synthetic bodies comprise pharmaceutically acceptable bodies have a conformation and size corresponding to mammalian apoptitic bodies wherein the surface of said pharmaceutically acceptable body has been modified to contain a plurality of ligands for one or more phosphatidylserine receptors; which biocompatible synthetic bodies are capable of binding to a phosphatidylscrine receptor on an antigen presenting cell when administered to the mammalian patient.  
     
     
         87 . The pharmaceutical composition of  claim 86  wherein the biocompatible non-liposomal synthetic body is selected from hydroxyethylcellulose, polyethylene glycol, hydroxethyl starch, polyvinylpyrrolidone, polysaccharides, polystyrene and agarose.  
     
     
         88 . The pharmaceutical composition of  claim 86  wherein said biocompatible non-liposomal synthetic bodies have a diameter of about 50 nanomenters—500 microns.  
     
     
         89 . The pharmaceutical composition of  claim 88  wherein said biocompatible non-liposomal synthetic bodies have a diameter of about 50 nanomenters—1000 nanometers.  
     
     
         90 . The pharmaceutical composition of  claim 86  comprising a unit dosage form.  
     
     
         91 . A process for alleviating the symptoms of a disorder in a mammalian patient, which comprises administering to the patient an effective amount of PS-carrying bodies as defined herein, wherein the disorder is an inflammatory disorder, an endothelial dysfunction disorder or an inappropriate cytokine expression disorder.  
     
     
         92 . Lyophilized or freeze dried PS-carrying bodies.  
     
     
         93 . A kit of parts comprising the lyophilized or freeze dried PS-carrying bodies of claim  46  and a pharmaceutically acceptable carrier.  
     
     
         94 . The kit of  claim 93  wherein the pharmaceutically acceptable carrier is selected from physiological sterile saline, sterile water, pyrogen-free water, isotonic saline, and phosphare buffer solution.