The novel positively charged pro-drugs of NSAIAs in the general formulas (1,2a, 2b, 2c, or 2d) "Structure 1, 2a, 2b, 2c, or 2d" were designed andsynthesized. The compounds of the general formulas (1, 2a, 2b, 2c, or 2d) "Structure1, 2a, 2b, 2c, or 2d" indicated above can be prepared from metal salts, organicbase salts, or immobilized base salts of NSAIAs with suitable halide compounds.The positively charged amino groups in the pro-drugs in this invention largelyincrease the solubility of the drugs in water and will bond to the negative chargeon the phosphate head group of membrane. Thus, the local concentration of theoutside of the membrane or skin will be very high and will facilitate the passageof these pro-drugs from a region of high concentration to a region of low concentration.This bonding will disturb the membrane a little bit and may make some room for thelipophilic portion of the pro-drug. When the molecules of membrane move, themembrane may "crack" a little bit due to the bonding of the pro-drug.This will let the pro- drug insert into the membrane. At pH 7.4, only about 99% ofthe amino group is protonated. W hen the amino group is not protonated, the bondingbetween the amino group of the pro-drug and the phosphate head group of the membranewill disassociate, and the pro-drug will enter the membrane completely. Whenthe amino group of the pro-drug flips to the other side of the membrane and thusbecomes protonated, then the pro-drug is pulled into the cytosol, a semi- liquidconcentrated aqueous solution or suspension. These pro-drugs can be used fortreating and preventing diabetes (type I or/and type II), abnormal blood glucoseand lipid levels, stroke, heart attack, and other heart and vascular diseasesAlzheimer's diseases, Parkinson's diseases and other neurodegenerativediseases, psoriasis, discoid lupus erythematosus, systemic lupus erythematosus(SLE), autoimmune
