Esflurbiprofen/Mentha Oil

Smoke flavorings are mixtures generated from wood pyrolysis that are filtered to remove tar and are often considered healthier alternatives to conventional smoking processes. While the latter is mostly unregulated, smoke‐flavoring primary products (SFPPs) are undergoing the 10‐year required re‐evaluation in the European Union (EU). To comply with recent smoke flavor guidance, in vivo micronucleus studies in rats and transgenic rodent (TGR) mutation assays in Muta™Mice were conducted on three SFPPs. For most studies, typical limit doses were exceeded to comply with regulatory requests. Exposure to SFPPs by oral gavage did not result in significant increases in bone marrow micronucleus formation. Except for one group, exposure to SFPPs via feed for 28 days did not result in significant increases in mutant frequency (MF) in the glandular stomach or liver. One group exposed to a maximal feasible dietary dose of 50,000 ppm (>10,000 mg/kg bodyweight per day) exhibited a statistically significant increase in liver MF; however, the MF in all mice in this group were within the historical vehicle control 95% quantile confidence intervals and therefore not considered biologically relevant. Based on estimates of human dietary exposure to each SFPP, the margin of exposure (MOE) values in the TGR assays exceed 10,000. The MOE for one unintentionally present constituent, 2,5(H)‐furanone, also exceeds 10,000. Collectively, these data indicate that these SFPPs pose no genotoxic risk and are safe alternatives to conventional smoking.

S-flurbiprofen plaster (SFPP) is highly skin permeable and represents a new conservative treatment for knee osteoarthritis (KOA) that can attain considerably higher concentrations in the synovium than topical flurbiprofen. To date, no study has investigated the efficacy and adherence rate of SFPP in patients with end-stage KOA. This study aimed to compare the effectiveness and adherence rate of SFPP for pain management in patients with moderate and end-stage KOA.

This retrospective study included a total of 118 patients with KOA (Kellgren-Lawrence classification grades II (n = 29), III (n = 32), and IV (n = 57)). The difference in SFPP use rate, adverse drug reactions rate, whether 50% pain relief occurred, and the percentage of patients who underwent surgical treatment were calculated.

The overall SFPP use rate at one year was 61.0% (88.1% at less than one month, 79.7% at three months, and 61.0% at six months), with no significant differences among Kellgren-Lawrence grade II, III, and IV groups (p = 0.538). Adverse drug reactions such as skin rash (n = 23), skin irritation (n = 8), and gastrointestinal disorders (n = 2) were observed. The one-year SFPP use rate was significantly lower in patients in whom these side effects occurred but did not decrease in patients in whom only a skin rash occurred. Overall, 19 patients underwent surgery after discontinuation of SFPP use. Surgery was statistically selected more by the "over 71 years of age" group (p = 0.038) and the "ineffective" group (p = 0.007).

SFPP exerts a comparable therapeutic effect even in end-stage KOA and may be an effective treatment option. Even if patients have end-stage KOA, there are cases in which the patient's background does not allow for surgery positively, such as high perioperative risk or desire for conservative treatment. In such cases, SFPP may be an effective treatment option worth trying.