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sitagliptin phosphate + ipragliflozin L-proline (Sujanu / MK0431J)

✓ Approved

Kotobuki Pharmaceutical Co., Ltd. · DPP4 · 小分子

什么是 sitagliptin phosphate + ipragliflozin L-proline？

sitagliptin phosphate + ipragliflozin L-proline 是一种小分子，由Kotobuki Pharmaceutical Co., Ltd.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Sujanu, MK0431J
公司Kotobuki Pharmaceutical Co., Ltd.
药物类别小分子
分子靶点DPP4, SLC5A2
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Kotobuki Pharmaceutical Co., Ltd.

作用机制

分子靶点

sitagliptin phosphate + ipragliflozin L-proline 作用于 2 个分子靶点：

DPP4dipeptidyl peptidase 4 (CD26, DPPIV)
SLC5A2solute carrier family 5 member 2 (SGLT2)
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

sitagliptin phosphate + ipragliflozin L-proline 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Metabolism and nutrition disordersType 2 diabetes mellitus✓ Approved

相关研究文献

PubMedFrontiers in pediatrics2026-09-11

Association between serum phosphate levels and outcome among critically ill newborns: a retrospective cohort study.

Bao Lisha L, Liu Xiaohui X, Zhao Caixia C, Li Jing J et al.

This study aimed to explore the relationship between serum phosphate levels and clinical outcomes in critically ill neonates. A retrospective cohort study was conducted using the Pediatric Intensive Care (PIC) database from (2010- 2018.) Multivariable regression models, generalized additive models, and threshold effect analysis were adopted to evaluate the relationship between serum phosphate levels within 24 h of ICU admission (Pi24) and neonatal outcomes. A total of 1,902 critically ill neonates were enrolled. Pi24 was stratified into three tertile groups (Q1-Q3). Baseline characteristics and Kaplan-Meier curves showed that higher Pi24 correlated with higher 28-day mortality, peaking at 11% in the Q3 group. Multivariate Cox proportional hazards regression analysis revealed that, Q3 neonates had a 76% increased risk of 28-day mortality compared with Q1(HR = 1.76, 95%CI:1.08∼2.88, P = 0.025), Multivariate logistic regression indicated an 80% higher odds of in-hospital death in Q3 vs. Q1(OR = 1.80, 95%CI: 1.1-2.95, P = 0.019). Within Pi24 ranged from 1.76 to 4.37 mmol/L, each 1.0 mmol/L elevation in serum phosphate level increased in-hospital death risk by 45.6% (OR = 1.456, 95% CI: 1.039-2.039, P = 0.029). Multivariate linear regression analysis revealed that Q1 neonates had significantly longer hospital LOS than Q3 (β = -4.68, 95% CI: -7.84∼-1.53, P = 0.004). Threshold effect analysis further demonstrated that when serum phosphate was < 2.5 mmol/L, each 1.0 mmol/L reduction prolonged hospital LOS by 6.89 days (β = -6.892, 95% CI: -10.801∼-2.983, P = 0.001). Elevated Pi24 levels were associated with increased risks of 28-day mortality and in-hospital death in critically ill neonates, while lower Pi24 levels independently predict prolonged hospital LOS Pi24 may represent a valuable prognostic biomarker for this population.

PMID 42723969
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PubMedFrontiers in endocrinology2026-09-11

Pre-treatment serum phosphate as a metabolic correlate of live birth after IVF/ICSI: a retrospective cohort study.

Wang Zhilong Z, Shen Xiaoyue X, Shi Qingqing Q, Yan Yuan Y et al.

Oocyte developmental competence is influenced by the systemic metabolic milieu during folliculogenesis. Inorganic phosphate is essential for ATP synthesis, nucleic acid metabolism, and phosphorylation-dependent signalling, but its relationship with assisted reproductive technology outcomes remains unclear. We investigated whether pre-treatment fasting serum phosphate was associated with live birth after first IVF/ICSI fresh embryo transfer. This retrospective cohort study included 2, 226 women aged 20-42 years undergoing their first IVF/ICSI cycle with fresh embryo transfer between January 2022 and June 2024. Serum phosphate was measured before ovarian stimulation and analysed as quartiles and per 1-SD increase (0.146 mmol/L). Multivariable logistic regression assessed associations with live birth, adjusting for demographic, ovarian reserve, metabolic, and treatment-related factors. Restricted cubic splines evaluated dose-response relationships. Measurement-window analyses stratified participants by the interval between biochemistry assessment and oocyte retrieval. The overall live birth rate was 60%, increasing from 56% in the lowest phosphate quartile to 66% in the highest (P for trend = 0.003). Each 1-SD increase in serum phosphate was associated with higher odds of live birth (adjusted OR 1.15, 95% CI 1.06-1.26; P = 0.002), with a linear dose-response (P for non-linearity = 0.305). Serum phosphate was not associated with MII oocyte count or usable embryo count. In measurement-window analyses, the association was consistent in the 60-120 day window (n = 1, 485; adjusted OR 1.18, 95% CI 1.03-1.35) and the 120-180 day window (n = 637; adjusted OR 1.16, 95% CI 1.01-1.34). The 0-60 day stratum was underpowered (n = 104). Additional adjustment for calcium, alkaline phosphatase, fasting glucose, and trigger-day progesterone did not materially alter the results. Higher pre-treatment serum phosphate was associated with higher odds of live birth after IVF/ICSI, independent of oocyte yield. External validation and mechanistic studies are required before clinical application.

PMID 42723787
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PubMedThe Journal of dairy research2026-09-11

Whole-genome safety assessment of Loigolactobacillus coryniformis WBB05 and identification of a candidate gene for aerobic reuterin production.

Tsuda Harutoshi H

This study reports on the safety profile of Loigolactobacillus coryniformis WBB05 for food industry applications and identifies glycerol-3-phosphate oxidase (GlpO) as a candidate gene associated with aerobic reuterin production. The safety of L. coryniformis WBB05 was evaluated through whole-genome sequencing, phenotypic analysis of haemolytic activity and determination of minimum inhibitory concentrations (MICs) of antibiotics. Comparative genomic analysis was performed to identify candidate genetic determinants for aerobic reuterin production. The draft genome (2.83 Mb, 179 contigs) harboured no known virulence factors, acquired antimicrobial resistance (AMR) genes or biogenic amine biosynthetic genes. Prophage analysis identified only one incomplete prophage region, and four CRISPR-Cas systems (212 spacers) were consistent with phage defence capacity. Secondary metabolite analysis revealed biosynthetic gene clusters encoding a coagulin-like bacteriocin. No β-haemolytic activity was observed. The MICs of all antibiotics tested were below the European Food Safety Authority cut-off values except for kanamycin (128 mg/L), although no acquired AMR genes were detected. Comparative genomic analysis revealed that L. coryniformis WBB05 possesses two putative copies of GlpO, a gene not detected in publicly available genomes of Limosilactobacillus reuteri, which produces reuterin only under anaerobic conditions. These findings support the use of L. coryniformis WBB05 as a safe adjunct culture for dairy applications and highlight GlpO as a candidate determinant of aerobic reuterin production. Further studies comparing GlpO-positive and GlpO-negative strains under aerobic and anaerobic conditions are warranted to confirm the role of GlpO.

PMID 42723509
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PubMedJournal of thoracic disease2026-09-11

Hybrid chest wall reconstruction using a composite scaffold and mesh: a surgical technique.

Borges Enzo Campedelli EC, D'Ambrosio Paula Duarte PD, Marchesi Alana Cozzer AC, Macedo João Paulo JP et al.

Chest wall reconstruction after oncologic resection or for congenital defects such as Poland syndrome poses significant technical challenges. Available reconstructive options present distinct limitations: synthetic meshes provide immediate mechanical support but are biologically inert, rigid prostheses carry higher infection risk and limited adaptability, and biologic matrices may lack early structural rigidity. Here, we describe a hybrid reconstruction technique that combines a double-layer Marlex® mesh (Davol Inc., Cranston, RI, USA) with a Vitagraft® bioactive scaffold (DMC Equipamentos, São Carlos, SP, Brazil)-composed of β-tricalcium phosphate and poly-L-lactic acid. The technique was initially developed for Poland syndrome and is equally applicable to oncologic full-thickness chest wall resections. The Marlex mesh is shaped to the defect and anchored circumferentially to the rib margins with nonabsorbable interrupted sutures, providing immediate mechanical stability. Vitagraft blocks are softened in sterile water at 70 ℃, custom-molded to the defect-with the possibility of reheating two to three times for progressive adjustment-and fixed over the mesh using the same cardinal sutures. Direct scaffold-to-rib-bone-edge contact (avoiding costal cartilage) is essential to promote osteoconductive integration and biological incorporation. The reconstruction is covered with a vascularized muscle flap, typically pectoralis major or serratus anterior, followed by layered closure over submuscular drains. In congenital cases with muscle aplasia, subcutaneous tissue may be used for coverage. Institutional experience confirms reproducible and safe results after overcoming the initial learning curve. This hybrid technique offers an anatomically adaptable, biologically active solution for complex chest wall defects across oncologic and congenital indications, combining the mechanical strength of Marlex mesh with the osteoconductive potential of the Vitagraft scaffold.

PMID 42724271
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PubMedBMC sports science, medicine & rehabilitation2026-09-11

Comparative effects of long- and short-interval aerobic high-intensity interval training on glycemic control among individuals with type 2 diabetes: a network meta-analysis.

Hu Xuanming X, Wen Meilin M, Liu Shunfang S

This study aimed to systematically compare and rank the relative efficacy of moderate-intensity continuous training (MICT), short-interval high-intensity interval training (HIIT-S), and long-interval HIIT (HIIT-L) on glycemic control among individuals with type 2 diabetes (T2D) using a network meta-analysis (NMA). Following the PRISMA-NMA guidelines, we searched PubMed, Embase, Cochrane Library, and Web of Science from database inception to October 24, 2025. Randomized controlled trials (RCTs) comparing the effects of HIIT, MICT, or non-exercise control (CON) on glycemic outcomes among individuals with T2D were included. Based on the intensity of training and durations of each high-intensity interval, aerobic HIIT was further classified into HIIT-S (≤ 60 s) and HIIT-L (≥ 2 min). The primary outcomes were glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG). The homeostatic model assessment for insulin resistance (HOMA-IR) was included post hoc as an exploratory secondary outcome. A Bayesian NMA using random-effects models was implemented using the gemtc package in R. Effect sizes were expressed as mean differences (MDs) with 95% credible intervals (CrIs), and interventions were ranked through the Surface Under the Cumulative Ranking curve (SUCRA). This study was prospectively registered on PROSPERO (CRD420251175046). In total, sixteen RCTs involving 744 participants with T2D were included. Among them, fifteen studies reported HbA1c, thirteen reported FPG, and seven reported HOMA-IR. For HbA1c, MICT (MD = - 0.47, 95% CrI: -0.77 to - 0.17), HIIT-S (MD = - 0.50, 95% CrI: -0.84 to - 0.18), and HIIT-L (MD = - 0.85, 95% CrI: -1.16 to - 0.55) all significantly reduced HbA1c levels relative to CON. Moreover, HIIT-L was significantly more effective than MICT (MD = - 0.38, 95% CrI: -0.76 to - 0.01), whereas no significant difference was observed between HIIT-L and HIIT-S (MD = - 0.34, 95% CrI: -0.76 to 0.08). However, the HIIT-L versus MICT comparison was no longer statistically significant in a sensitivity analysis excluding Winding et al. (MD = - 0.35, 95% CrI: -0.74 to 0.05). For FPG, MICT (MD = - 0.77, 95% CrI: -1.10 to - 0.43), HIIT-S (MD = - 0.85, 95% CrI: -1.21 to - 0.52), and HIIT-L (MD = - 1.12, 95% CrI: -1.54 to - 0.70) all significantly reduced FPG levels relative to CON, whereas no significant differences were observed among the active exercise interventions. Based on the SUCRA rankings, HIIT-L ranked highest for both HbA1c (97.41%) and FPG (92.31%). For HOMA-IR, only HIIT-L showed a significant reduction compared with CON (MD = - 0.84, 95% CrI: -1.74 to - 0.06), whereas MICT and HIIT-S did not. However, because HOMA-IR was included post hoc as an exploratory outcome, and because the available evidence was limited and produced wide credible intervals, these findings should be interpreted cautiously. Current evidence indicates that MICT, HIIT-S, and HIIT-L are all associated with reductions in HbA1c and FPG compared with CON among individuals with T2D. HIIT-L had the highest ranking probabilities and the largest point estimates for both outcomes. Although the primary analysis suggested a greater reduction in HbA1c with HIIT-L than with MICT, this comparison was not robust to the exclusion of Winding et al. HIIT-S also improved glycemic control and may represent a practical alternative because each high-intensity work interval is shorter, although its feasibility and tolerability require direct evaluation. Future high-quality, volume-matched RCTs directly comparing HIIT-S and HIIT-L are needed to clarify the clinical utility of different aerobic HIIT protocols for T2D. PROSPERO CRD420251175046.

PMID 42723103
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PubMedIranian journal of pharmaceutical research : IJPR2026-09-11

Integrative Network Analysis of Bioactive Compounds from Punica granatum L. Peel: Multi-Target Mechanisms in Wound Healing.

Shokri Seyyed Shahab SS, Salimi Sabour Ebrahim E, Hosseini Seyed Morteza SM, Shateri Hossein Reza HR

Wound-healing agents often have limited efficacy and require prolonged recovery times, prompting growing interest in developing herbal-based formulations. Among these, Punica granatum L. has attracted considerable attention because of its high polyphenolic content. Despite its widespread use, the precise pharmacological targets underlying its wound-healing effects remain poorly understood and require systematic investigation. This study aimed to elucidate the underlying pharmacological mechanisms of the topical wound-healing properties of P. granatum L. using a network pharmacology approach. Bioactive compounds of P. granatum L. and their potential target genes were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Similarity Ensemble Approach (SEA), and SwissTargetPrediction databases. Wound healing-related genes were retrieved from the GeneCards database. Genes intersecting P. granatum L. targets and wound healing-associated genes were subjected to functional enrichment analyses, including protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The PPI network was further analyzed using Cytoscape, and the phytoconstituent-target interaction network was visualized using Gephi. These findings were validated using molecular docking. A total of 40 intersecting genes were identified as potential P. granatum L. targets involved in wound healing. Among these, EGFR, PTPN11, HRAS, IGF1R, and ESR1 were identified as key hub genes. Functional enrichment analysis indicated that the most significantly enriched signaling pathways included the MAPK, PI3K-Akt, EGFR tyrosine kinase inhibitor resistance, focal adhesion, and FoxO signaling pathways. Molecular docking analysis confirmed favorable binding of quercetin and ellagic acid to the hub targets EGFR, IGF1R, and ESR1. These findings elucidate the pharmacological pathways underlying P. granatum-mediated wound healing and suggest that P. granatum L. acts as a multi-target modulator in the wound-healing process.

PMID 42724347
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