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celecoxib + tramadol HCl (MR308 / Velyntra / Seglentis)

✓ Approved

Kowa · OPRM1 · 小分子

什么是 celecoxib + tramadol HCl？

celecoxib + tramadol HCl 是一种小分子，由Kowa研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名MR308, Velyntra, Seglentis
公司Kowa
药物类别小分子
分子靶点OPRM1, PTGS2, SLC6A2, SLC6A4
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Kowa

作用机制

分子靶点

celecoxib + tramadol HCl 作用于 4 个分子靶点：

OPRM1opioid receptor mu 1 (MOP, M-OR-1)
PTGS2prostaglandin-endoperoxide synthase 2 (PHS-2, PGG/HS)
SLC6A2solute carrier family 6 member 2 (NAT1, NET)
SLC6A4solute carrier family 6 member 4 (SERT1, 5-HTTLPR)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

celecoxib + tramadol HCl 针对 2 个适应症，涉及 2 个治疗领域。

治疗领域疾病/病症分期
Gastrointestinal disordersAbdominal pain✓ Approved
Injury, poisoning and procedural complicationsProcedural painPhase III

相关研究文献

PubMedArthritis & rheumatology (Hoboken, N.J.)2026-10-27

Comparative risks of mortality and fractures in patients with osteoarthritis initiating tramadol versus other opioids.

Sreedharas Sushama Kattinakere SK, Bea Sungho S, Huybrechts Krista F KF, Khan Nazleen F NF et al.

Tramadol is commonly used to manage pain in patients with osteoarthritis, but its comparative safety in this population remains largely unknown. The study aimed to evaluate the risks of all-cause mortality and fracture among patients with osteoarthritis initiating tramadol versus other prescribed opioids. We conducted a retrospective cohort study using Optum Clinformatics® Data Mart (2005-2021). Adults aged ≥50 years with osteoarthritis initiating tramadol, codeine, hydrocodone, or oxycodone were included. Outcomes were all-cause mortality and fractures. Propensity score weighting balanced baseline characteristics, and weighted Cox proportional hazards models estimated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Among 1,057,635 patients (mean age 69.1 years; 62.5% female), 294,760 initiated tramadol, 97,048 codeine, 474,733 hydrocodone, and 191,094 oxycodone. During follow-up, 9,988 deaths and 10,455 fractures occurred. Tramadol showed similar mortality risk to codeine (HR 0.93, 95% CI 0.73-1.19), but lower risk compared with hydrocodone (HR 0.81, 95% CI 0.70-0.93) and oxycodone (HR 0.40, 95% CI 0.34-0.47). Fracture risk was comparable to codeine (HR 1.10, 95% CI 0.96-1.25) and lower than hydrocodone (HR 0.91, 95% CI 0.83-0.98) and oxycodone (HR 0.83, 95% CI 0.75-0.93). In adults aged 50 years or older with osteoarthritis initiating an opioid, tramadol initiation was associated with lower risks of mortality and fractures compared with hydrocodone and oxycodone, and similar risks compared with codeine. These findings suggest that tramadol may be a comparatively favorable option when opioid therapy is necessary, although its longer-term comparative safety remains uncertain.

PMID 42935370
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PubMedPharmaceutics2026-10-27

Engineering Chitosan-Coated PLGA Nanoparticles for Sustained Bupivacaine Delivery: Physicochemical Performance and a Preliminary Fibroblast Cytocompatibility Assessment.

Çamlik Gamze G, Kuşman Sayği Tuba T, Nalci Kemal Alp KA

Background/Objectives: Bupivacaine hydrochloride (Bupi-HCl) is a widely used local anesthetic; however, rapid diffusion from the site of administration and concentration-dependent cytotoxicity may limit its local therapeutic efficacy. This study aimed to develop chitosan-coated poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles for sustained Bupi-HCl delivery and to evaluate their physicochemical properties, release behavior, long-term stability, and cytocompatibility with fibroblasts. Methods: Bupi-HCl-loaded chitosan-coated PLGA nanoparticles (Bupi-CS-PLGA NPs) were prepared using a modified double-emulsion solvent-evaporation method and characterized by TEM, DLS, FTIR, DSC, XRD, encapsulation efficiency (EE), drug loading (DL), in vitro release, release kinetic modeling, 12-month physicochemical stability, and a preliminary MTT-based fibroblast cytocompatibility assessment. Results: Bupi-CS-PLGA NPs exhibited a predominantly spherical morphology, a mean particle size of 175.13 ± 8.10 nm, a PDI of 0.195 ± 0.026, and a zeta potential of +24.86 ± 1.90 mV. EE and DL were 80.00 ± 2.14% and 2.60 ± 0.11%, respectively. FTIR findings were consistent with physical incorporation of Bupi-HCl within the PLGA/chitosan matrix without evidence of new chemical bond formation, while DSC demonstrated differences in the thermal profiles of the nanoparticle formulations and XRD showed that Bupi-HCl was not detectable as a separate crystalline phase. The nanoparticles provided sustained Bupi-HCl release over 72 h, reaching approximately 79-80% cumulative release compared with 97-98% for free Bupi-HCl. Among the evaluated kinetic models, Modified Langmuir and RRSBW yielded the highest coefficients of determination (R2 = 0.9958 and 0.9952, respectively), while RRSBW showed the lowest total residual value (19.5851). Physicochemical characteristics were maintained during 12 months of storage at refrigerated and room temperatures. Within one experimental run, empty CS-PLGA NPs showed no decrease in MTT-derived signal across the tested concentration range. Bupi-CS-PLGA NPs showed lower MTT-derived signal at 250 and 500 µg/mL than at the two lower particle concentrations (62.5 and 125 µg/mL); particle-related assay interference was not excluded. Because free and encapsulated Bupi-HCl were not evaluated at dose-equivalent concentrations, their cytotoxic potency could not be directly compared, and these single-experiment findings are reported as a preliminary assessment. Conclusions: Bupi-CS-PLGA NPs provided sustained drug release and long-term physicochemical stability, together with a preliminary, assay-limited fibroblast MTT assessment. These findings support further evaluation of this biodegradable nanoparticle system for sustained local delivery of Bupi-HCl.

PMID 42942855
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PubMedDalton transactions (Cambridge, England : 2003)2026-10-27

Acid medium effects on scandium extraction and coordination chemistry with an amine-triamide extractant for red mud processing.

Wang Xueyu X, Li Shimeng S, Yu Qiao Q, Wang Yiting Y et al.

The recovery of scandium from red mud meets two intertwined challenges: the overwhelming abundance of coexisting impurities, which renders conventional extractants poorly selective, and the lack of a systematic understanding of how the acid medium modulates extractant coordination chemistry and, consequently, separation efficiency. To address this, we comprehensively investigated the extraction and coordination of Sc3+ with the tripodal amine-triamide extractant NTAamide (n-Oct) (denoted as L) in HNO3, HCl, and H2SO4 media. Slope analysis and spectroscopic titration consistently confirm the formation of stable 1 : 2 Sc : L complexes in all three systems. Mechanistic studies further reveal that the ligand affinity toward Sc3+ decreases in the order NO3- > Cl- > SO42-, which originates from the varying strength of Sc3+-anion interactions, and together with differences in anion hydration energies, leads to the extraction efficiency sequence of HNO3 > HCl > H2SO4. Notably, in the most favorable HNO3 system, the separation factors of Sc3+ over common impurities (Na+, Mg2+, Al3+, Ca2+, Ti4+, Mn2+, Fe3+, and Y3+) reach 102-104 at 0.01 mol L-1 HNO3 and remain remarkably high even at 5.0 mol L-1, substantially outperforming conventional extractants. To fill this critical knowledge gap, we establish, for the first time, a direct correlation between the acid medium, the coordination chemistry of N,O-donor extractants, and the resulting extraction performance, thereby providing a rational and predictive framework for selecting optimal acid media for this class of extractants in red mud processing.

PMID 42937519
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PubMedPharmaceutics2026-10-27

Spray-Dried Chitosan-Clay Nanocomposite Gels as Binders: Enhanced Compressibility and Micromeritic Properties of Lactose-Based Granules for Poorly Compressible Drug Tablets.

Jarungsirawat Rapee R, Tabboon Peera P, Jaipakdee Napaphak N, Sakloetsakun Duangkamon D et al.

Background/Objectives: Nanocomposites of chitosan (CH) and magnesium aluminum silicate (MAS) clay can be produced by spray drying. This study aimed to characterize and evaluate spray-dried chitosan (SDCH) and SDCH-MAS nanocomposites, which were prepared using CH with MWs of 400 kDa (4M) and 800 kDa (8M), as binders of lactose granules containing propranolol HCl (PPN) and crude powder from Andrographis paniculata (ADP) intended for tablet formulation. Methods: Lactose granules were produced using SDCH and SDCH-MAS composites via wet granulation, and the granule properties were compared with those obtained using polyvinylpyrrolidone (PVP K30). The lactose granules incorporating PPN and ADP crude powder were also prepared and compressed into tablets. The physical properties of both granules and tablets were evaluated. Results: SDCH-MAS composites formed intercalated or exfoliated nanocomposites, as proved by PXRD, and rapidly hydrated in water to form gels that functioned as binders. Lactose granules prepared with SDCH and SDCH-MAS composites exhibited fair to good flowability and demonstrated lower yield pressure and yield strength during plastic deformation than those prepared with PVP K30. Moreover, granules loaded with PPN offered acceptable flowability and could be compressed into tablets. Increasing MAS content reduced the disintegration time of tablets in 0.1 N HCl. The use of SD4MCH in tablets could retard PPN release, while the addition of MAS accelerated drug release. For ADP crude tablets with a 75:25 ADP-to-lactose ratio, acceptable hardness and friability were achieved when SD4MCH-MAS 1:0.6 composites and PVP K30 were used, and 75% of andrographolide dissolved within 30 min. Conclusions: SDCH-MAS nanocomposite gels are effective binders for lactose granules in wet-granulated tablets.

PMID 42942795
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PubMedPolymers2026-10-27

Ultrasound-Assisted Recovery of Pectic Fractions from Grape Pomace: Combined Effects of Acid Type, pH, and Temperature on Physicochemical and Antioxidant Properties.

Brahmi Mohamed M, Moumnassi Sara S, Gharsallaoui Adem A

Grape pomace represents an underexploited source of pectic polysaccharides whose properties are strongly influenced by extraction conditions. This study investigated the combined effects of acid type (citric acid or HCl), pH (1.5, 2.0 and 3.0), and temperature (55, 65 and 85 °C) on pectic fractions recovered from grape pomace using sequential ultrasound-assisted extraction followed by dynamic maceration. A 2 × 3 × 3 full-factorial design was applied, combining citric acid or hydrochloric acid, three pH values (1.5, 2.0 and 3.0) and three temperatures (55, 65 and 85 °C), resulting in 18 extraction conditions. The recovered fractions were characterized in terms of extraction yield, degree of esterification (DE), methoxyl content (MeO), anhydrouronic acid content (AUA), molecular weight (Mw), apparent viscosity, carbohydrate and protein contents, color, FTIR profile, total phenolic content (TPC) and antioxidant activity. Extraction yield ranged from 1.12 to 7.88%, with the highest recovery obtained using citric acid at pH 3.0 and 55 °C. DE varied markedly from 14.89 to 63.63%, with citric acid consistently yielding low-methoxyl fractions under all conditions, whereas HCl at pH 1.5 yielded high-methoxyl fractions. MeO varied accordingly from 1.66 to 7.65%, while AUA remained within a comparatively narrow range of 63.27-69.24%, close to that measured for commercial citrus pectin (67.21%). Molecular weight ranged from 22.7 to 607 kDa, and increasing extraction temperature generally reduced both Mw and apparent viscosity, indicating greater structural modification under harsher conditions. FTIR spectra confirmed the preservation of the characteristic pectic polysaccharide framework while revealing differences in the carboxyl and fingerprint regions among extraction conditions. The recovered fractions contained 180.22-310.78 mg glucose eq./g total carbohydrate and 8.56-32.83 mg BSA eq./g protein. Phenolic compounds were also retained, with TPC values of 9.50-14.29 mg GAE/g and ABTS IC50 values ranging from 4.26 to 10.38 mg/mL. The factorial analysis demonstrated significant interactions among acid type, pH, and temperature for the main physicochemical and functional responses. Overall, the results demonstrate that these extraction variables can be adjusted to recover grape pomace pectic fractions with distinct esterification, molecular and antioxidant profiles.

PMID 42942586
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PubMedClinical and molecular hepatology2026-10-27

O-GlcNAcylation of GSDMD promotes mitochondrial dysfunction and hepatocyte injury in MASLD.

Wang Xue X, Jiang Mingzuo M, Xie Ning N, Chen Xinyu X et al.

Cell-membrane gasdermin D (GSDMD) plays a key role as a pyroptosis executor of metabolic dysfunction-associated steatohepatitis (MASH). However, the mitochondrial translocation of GSDMD occurs even during the metabolic dysfunction-associated steatotic liver (MASL) phase, which involves mainly hepatic steatosis without tremendous inflammatory responses or sustainable hepatic cell death; the underlying mechanism is unknown. We investigated the role of GSDMD in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). Liver tissues from patients with MASLD and control subjects were obtained to evaluate GSDMD expression and distribution. GSDMD△hep mice and their floxed littermate controls, GSDMDfl/fl mice, were fed a high-fat, high-cholesterol diet (HFHCD) for 4 and 12 weeks to develop MASL or MASH, respectively. Additionally, GSDMD△hep mice were administered an adeno-associated virus 8 (AAV8) vector expressing wild-type GSDMD (GSDMD-WT) or GSDMD O-GlcNAcylation site mutants (GSDMD-T174/S178A) and were provided with an HFHCD or a methionine-choline-deficient diet. GSDMD expression and mitochondrial translocation were increased in patients and experimental mice with MASLD. The translocation of GSDMD-NT to mitochondria impaired the mitochondrial membrane potential and promoted the leakage of cytochrome c and mitochondrial DNA, thus inducing early hepatocyte apoptosis, and was required for pyroptosis in MASLD. O-GlcNAcylation at T173/T175 (in humans) or T174/S178 (in mice) of GSDMD was responsible for GSDMD mitochondrial translocation and mitochondrial dysfunction. Targeting O-GlcNAcylation with Celecoxib suppressed GSDMD mitochondrial translocation and the development of MASLD. Targeting mitochondrial GSDMD-mediated programed cell death (PCD) pathways may provide new insights into the potential theoretical basis for MASLD interventions.

PMID 42935237
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