Purified phospholipid-non-steroidal anti-inflammatory drug associated compositions and methods for preparing and using same
View Patent ↗A new pharmaceutical composition is disclosed comprising a purified phospholipid-selective and/for nonselective non-steroidal, anti-inflammatory drug associated complex and methods for making and using same. A screening method for identifying compounds that form phospholipid associated complexes is also disclosed.
1. A method of preparing a phospholipid-non-steroidal anti-inflammatory drug composition comprising purified phospholipid-non-steroidal anti-inflammatory drug associated complexes comprising the steps of:
contacting a selective or nonselective non-steroidal anti-inflammatory drug (sns-NSAID) with an amount of phospholipid (PL) at a temperature between 40° C. and 60° C. in a polar solvent to produce a solution including the PL-sns-NSAID associated complexes, where the amount of the PL is in excess of an amount of the PL normally soluble in the solvent in the absence of the sns-NSAID and where the amount of the excess PL is below an amount based on the amount of sns-NSAID where the PL begins to precipitate out of the solution; and
substantially removing the polar solvent by evaporation to form a phospholipid-non-steroidal anti-inflammatory drug associated composition comprising purified PL-sns-NSAID associated complexes in the form of a homogenous oil; wherein a weight ratio of sns-NSAID to PL in the purified phospholipid-non-steroidal anti-inflammatory drug associated composition is between 1:2 and 1:4;
wherein the sns-NSAID is selected from the group consisting of ibuprofen, aspirin, salicylic acid, naproxen, indomethacin, diclofenac, fluobiprofen flurbiprofen, ketoprofen and mixtures or combinations thereof; and
wherein the polar solvent is acetone.
2. The method of claim 1 , wherein the phospholipid is one or more compounds of the general formula:
where R 1 and R 2 are saturated or unsaturated substitutions ranging from 8 to 32 carbon atoms; R 3 is H or CH 3 , and X is H or COOH; and R 4 is ═O or H 2 .
3. The method of claim 1 wherein the phospholipid is selected from the group consisting of phosphatidylcholine (PC), dipaimitoylphosphatidylcholine (DPPC), other disaturated phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositol, phosphatidyl serines sphingomyelin or other ceramides, lecithin oils derived from soy beans, dimyristoyl phosphatidylcholine, distearoylphosphatidylcholine, dilinoleoyiphosphatidylcholine (DLL-PC), soy phophatidylchioine (Soy-PC or PCs), egg phosphatidycholine (Egg-PC or PC), and mixtures or combinations thereof.
4. The method of claim 1 , further comprising:
prior to the removing step, cooling the solution for a cooling time and at a cooling temperature, where the cooling time and cooling temperature are sufficient to precipitate any PL not associated with the sns-NSAID or any PL in excess of an associated amount;
if a precipitate forms, centrifuging the cooled solution to form a precipitate and a supernatant; and
separating the precipitate from the supernatant.