OBJECTIVE To establish a determination method for the related substances of LPM3480392, a novel Gi protein-biased opioid receptor(MOR) agonist. METHODS The separation was carried out with Waters Symmetry Shield RP18 (150 mm×4.6 mm, 3.5 μm) by gradient elution method, using a mixture of 0.002 5 mol·L–1 sodium 1-octanesulfonate monohydrate in 0.01 mol·L–1 potassium dihydrogen phosphate-water solution(containing 0.1% triethylamine, adjusted pH to 2.50 with phosphate acid) and acetonitrile as the mobile phase at a flow rate of 1.0 mL·min–1 and the UV detection wavelength was set at 210 nm. RESULTS The chromatographic peaks of LPM3480392 and impurity A, impurity B, impurity C, impurity E and impurity F could be completely separated, the linear relationship of LPM3480392 was good in 0.064 9−5.191 2 μg·mL–1, while impurity A, impurity B, impurity C, impurity E and impurity F showed good linear relationship within 0.066 6−7.610 4 μg·mL–1, 0.166 0−3.794 0 μg·mL–1, 0.209 2−4.463 2 μg·mL–1, 0.167 9−7.672 6 μg·mL–1 and 0.016 4−7.505 7 μg·mL–1, respectively. The recovery rate was within 93.0%−103.2%. CONCLUSION The method is suitable for the determination of related substances in LPM3480392, and can provide valuable reference for the follow-up research and development of LPM3480392.

Objective To investigate the efficacy of 0.3%sodium hyaluronate combined with carbomer in the treatment of patients with dry eye.Methods A total of 80 patients with dry eye treated in Zhoushan Hospital from January 2019 to January 2022 were selected and divided into study group and control group according to random number table method,with 40 cases in each group.Patients in control group were treated with 0.3%sodium hyaluronate,and patients in study group were treated with carbomer on this basis.Ocular surface disease index(OSDI),visual function score,Schirmer test,inflammatory factors,and adverse reactions were compared between two groups.Results The total effective rate in study group was significantly higher than that in control group(χ2=4.804,P=0.028).After treatment,OSDI,visual function score,interleukin(IL)-6,tumor necrosis factor-α(TNF-α),and IL-1β of the patients in both groups were significantly lower than before treatment,and volume of tear secretion was significantly higher than before treatment(P<0.05).OSDI,visual function score,IL-6,TNF-α and IL-1β of study group were significantly lower than those of control group,and volume of tear secretion was significantly higher than that of control group(P<0.05).There was no significant difference in adverse reactions between two groups(χ2=0.180,P=0.671).Conclusion 0.3%sodium hyaluronate combined with carbomer has good efficacy in the treatment of dry eye disease,can improve the stability of tear film,enhance visual function,reduce the expression of inflammatory factors in tear,and has good safety.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

In this study, physical fingerprint and multivariate statistical analysis was applied to characterize the quality consistency of different sources of carboxymethylcellulose sodium, and the visualization of R language was used to explore the intrinsic correlation on its performances, and we drew contour maps between independent variables and flowability of powder to find the design space. Through the physical fingerprint and multivariate statistical analysis, it was found that there were differences in the powder properties of carboxymethylcellulose sodium from different sources, and its moisture content, bulk density and tapped density have a great influence on the fluidity. The fillibility was positively correlated with flowability, both negatively correlated with compressibility by R intelligent visualization analysis, which was statistically significant (P < 0.01). When the angle of repose is 30° - 40°, the appropriate design space was found as 5.092 2% < moisture content < 7.006 7%, 0.560 2 g·cm^-3 < bulk density < 0.579 9 g·cm^-3, and 0.646 3 g·cm^-3 < tapped density < 0.816 5 g·cm^-3. The results show that it is scientific and feasible to evaluate the quality consistency of pharmaceutical excipients by using the physical fingerprint, multivariate statistical analysis and visualization methods, which provides new ideas for the production and quality evaluation of excipients and the development of generic prescriptions.