Lysophosphatidylcholine (LPC), which is a major component of oxidized low-density lipoprotein, is known to have relatively beneficial effects on sepsis by activating various immunocompetent cells including monocytes, phagocytes, and neutrophilic leukocytes. In addition, it is known that the administration of LPC significantly lowers mortality due to peritonitis in peritonitis animal models and cecal ligation and puncture (CLP) animal models, and produces effects on the treatment of various bacterial infection diseases, including peritonitis, pneumonia, osteomyelitis, cellulites, osteomyelitis, and the like, through inherent immunity enhancement (Korean Patent Nos. 10-0842160 and 10-0849448). In addition, it is known that LPC can be used as a therapeutic agent for acute respiratory distress syndromes and multiple organ dysfunction syndromes (Korean Patent No. 10-0842159).
However, due to very low solubility in the aqueous phase, LPC compounds have limits in the development of stable pharmaceutical formulations, for example, the in vivo bioavailability of the LPC compounds is low when they are dissolved in the aqueous phase for preparing medicinal products, such as sterile water, injectable water, deionized water, and buffer solvent and then administered, or the LPC compounds are precipitated in the body fluid and tissues immediately after the in vivo administration even though they are solubilized formulations. Moreover, LPC compounds induce hemolysis and erythrocyte aggregation (Tanaka Y. et al., J Biochem. 94(3):833-40 (1983)), and exhibit remarkable local irritation of LPC itself at the time of subcutaneous administration in animal experiments (Ryborg A K, et al., Acta Derm Venereol. 80(4):242-6 (2000)). Therefore, the development of novel formulations for overcoming such defects is required.
Throughout the entire specification, many papers and patent documents are referenced and their citations are represented. The disclosure of cited papers and patent documents are entirely incorporated by reference into the present specification, and the level of the technical field within which the present invention falls, and details of the present invention are explained more clearly.
USPTO Backgrounds
USPTO Backgrounds