The morphological and structural characteristics of aqueous sodium dibutyl phosphate (DBP) have been investigated at all levels from molecular to superstructural by using polarized microscopy, light scattering, small-angle X-ray scattering, and nuclear magnetic resonance techniques. Above a certain concentration, the aqueous solutions separated into two liquid phases, one of which was spontaneously birefringent. The birefringent phase first separated in the form of spherulites, in which the hydrocarbon chains are oriented parallel to the radial direction. With increasing concentration, a transition from spherulitic to rodlike texture occurred and the system finally became a continuous birefringent phase. The spherulitic and/or rodlike textures were gradually destroyed with increasing temperature and disappeared at 55 degrees C. However, the X-ray scattered intensity distribution indicated that despite the disruption of superstructures at 70 degrees C, the bilayer blocks (assemblies) are maintained without separating into bilayer micell units which can be regarded as two weakly interacting monolayer composed of DBP. Above a critical concentration, the longitudinal and transverse relaxation times predicted that the motion of carbons is strongly restricted by hydrocarbon chain interaction.

The anti-pyretic activity of alminoprofen (AP), a non-steroidal anti-inflammatory agent, and its mode of action were investigated in conscious febrile rabbits. A fever was evoked by i.v. injection of lipopolysaccharide (LPS), intracisternal (i.c.) injection of leukocytic pyrogen (LP) or i.c. injection of arachidonic acid (AA). The amount of PGE2 or AP in the cerebrospinal fluid (CSF) after i.v. LPS was estimated using an RIA or HPLC method. AP (3-30 mg/kg, p.o.) dose-dependently inhibited the LPS (0.5 micrograms/kg, i.v.)-induced fever; AP, ibuprofen, indomethacin and pranoprofen had ED50 values of 9.64, 26.45, 4.41 and 11.91 mg/kg, p.o., respectively. PGE2 in the CSF was markedly increased during the elevation of body temperature after i.v. LPS (0.5 microgram/kg). AP (30 mg/kg, p.o.) markedly inhibited the increase in PGE2 that was observed in the CSF during fever developed in response to i.v. LPS (0.5 micrograms/kg). The AP concentration in the CSF 2 hr after AP (30 mg/kg, p.o.) was 2.86 x 10(-6) (1.15-4.57 x 10(-6) M, a concentration too low to inhibit PG synthesis. A dose-dependent fever was observed after i.c. LP (1-8 unit) or AA (10-100 micrograms). AP (30 mg/kg, p.o.) shifted the dose-response curves for the i.c. LP-induced fever to the right, but did not have any effect on the i.c. AA-induced fever. These results suggest that AP has a relatively potent anti-pyretic activity, and its mechanism of action involves competition with LP at a site in the CNS, but does not involve an inhibition of cyclooxygenase at a central site, which has been considered as an anti-pyretic mechanism of nonsteroidal anti-inflammatory drugs.

Effects of alminoprofen (AP), a non-steroidal anti-inflammatory agent, were investigated using several experimental gouty models. AP (3-30 mg/kg, p.o.) dose-dependently inhibited urate crystal-induced rat paw edema. AP (3-30 mg/kg, p.o.) inhibited the accumulation of exudate and decreased the total counts of leukocytes and the amount of PGE2 in a dose-dependent manner in sodium urate crystal-induced pleuritic rats. AP (0.3-10 mg/kg, p.o.) showed a dose-related analgesic activity on the pain response in sodium urate crystal-induced arthritic rats. AP (10(-5)-10(-3)M) inhibited the sodium urate crystal-induced beta-glucuronidase release from guinea pig neutrophils at more than 10(-4) M. AP (10(-5)-10(-3)M) did not inhibit the sodium urate crystal-induced production of O2- from guinea-pig neutrophils. AP (10(-6)-10(-4) M) inhibited dose-dependently the chemotaxis of leukocytes induced by chemotactic factors from guinea pig neutrophils stimulated with sodium urate crystals. AP (10(-6)-10(-4) M) inhibited the sodium urate crystal-induced production of PGE2 from rat peritoneal leukocytes in a dose-related manner. These results suggest that AP has a potent anti-inflammatory and analgesic activity in sodium urate crystal-induced inflammations, and these effects are exerted through its combined inhibitions of PGE2 synthesis, leukocyte chemotaxis and lysosomal enzyme release.

This study was conducted to clarify the antiinflammatory profile of EB-382, comparing it with those of ibuprofen and other antiinflammatory agents. EB-382 had a more potent inhibition on the acetic acid-induced intensive mouse intraperitoneal vascular permeability and carrageenin-induced rat hind paw edema, but a less potent inhibition on the ultraviolet-induced guinea-pig erythema and the prostaglandin biosynthesis in vitro than ibuprofen. The inhibition by EB-382 was equipotent to that of indomethacin on carrageenin-induced rat pleurisy and the zymosan air pouch, and it demonstrated a strong inhibition on the kallikrein and zymosan-induced intensive guinea-pig skin vascular permeability. EB-382 had a more effective activity on paper disk-induced granuloma and adjuvant arthritis, and it had a less potent action on the gastric mucosal membrane than ibuprofen. EB-382 had a weak action on histamine-induced rat back skin vascular permeability and heat-induced protein denaturation and hemolysis in vitro, as also shown by other test agents. The above results indicate that EB-382 will be useful as an antiinflammatory agent with a new pharmacological effectiveness besides possessing properties common to other acidic non-steroidal antiinflammatory agents in clinical studies.