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clodronate disodium (Abioklad / Mebonat / Ostac)

✓ Approved

Abiogen Pharma S.p.A. · SLC17A9 · 小分子

什么是 clodronate disodium？

clodronate disodium 是一种小分子，由Abiogen Pharma S.p.A.研发。该药已获批，用于治疗相关适应症，给药途径：Injectable (Others)、Intraarterial Injection、Intramuscular (IM) Injection。

药物档案

商品名Abioklad, Mebonat, Ostac
公司Abiogen Pharma S.p.A.
药物类别小分子
分子靶点SLC17A9
给药途径Injectable (Others), Intraarterial Injection, Intramuscular (IM) Injection
状态Approved
来源： ClinicalTrials.gov, Abiogen Pharma S.p.A.

作用机制

分子靶点

clodronate disodium 作用于 1 个分子靶点：

SLC17A9solute carrier family 17 member 9 (POROK8, VNUT)
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

clodronate disodium 针对 6 个适应症，涉及 3 个治疗领域。

治疗领域疾病/病症分期
Endocrine disordersHypercalcaemia of malignancy✓ Approved
Musculoskeletal and connective tissue disordersMusculoskeletal pain✓ Approved
Musculoskeletal and connective tissue disordersOsteoarthritis✓ Approved
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Cancer pain✓ Approved
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Breast cancerPhase III

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相关研究文献

PubMedFrontiers in bioengineering and biotechnology2026-08-06

Evaluation of the effects of a high-efficiency decontamination solution for sodium contamination on sodium burn wounds in rat skin.

Jiang Shen S, Zhang Teng T, Gu Xiaona X

To prepare a compound irrigation formulation for sodium contamination and evaluate its effects on wound pH regulation and early repair outcomes in a rat model of sodium-induced skin injury. A compound irrigation formulation for sodium contamination was prepared using glycine and ethylenediaminetetraacetic acid disodium salt as the principal formulation components. Sixty Sprague-Dawley rats were randomly assigned to five groups: no-irrigation group (NI), water irrigation group (WI), boric acid irrigation group (BA), Diphoterine irrigation group (DP), and decontamination solution group (DS), with 12 rats in each group. At 3 min after sodium contamination, wounds were treated with the corresponding interventions and irrigated for 15 min. Wound pH was monitored during irrigation, and wound healing was evaluated on day 14. Histopathological changes were assessed by hematoxylin and eosin (H&E) staining and semi-quantitative injury scoring, and collagen deposition was evaluated by Masson staining. The expression of PCNA, VEGF, α-SMA, and CD31 was detected by immunohistochemistry, and the levels of IL-1β, IL-6, IL-10, and TNF-α were measured by ELISA. The DS group showed a rapid reduction in wound alkalinity, and wound pH shifted toward a near-neutral range after 15 min of irrigation. Compared with the NI, WI, and BA groups, the DS group had a significantly higher wound healing rate on day 14 (P < 0.05). Histological analysis and semi-quantitative injury scoring showed better tissue preservation, reduced inflammatory cell infiltration, a lower histopathological injury score, and increased collagen deposition in the DS group. PCNA expression did not differ significantly among groups, whereas the expression levels of the angiogenesis- and repair-associated markers VEGF, α-SMA, and CD31 were increased in the DS group compared with the NI and WI groups (P < 0.05). In addition, IL-1β and TNF-α levels were decreased in the DS group compared with the NI and WI groups (P < 0.05), IL-6 was decreased compared with the NI group (P < 0.05), and IL-10 was increased compared with all other groups (P < 0.05). The compound irrigation formulation rapidly reduced wound alkalinity and was associated with improved early repair outcomes, including increased collagen deposition, enhanced angiogenesis-related marker expression, and a more favorable local inflammatory profile in sodium-induced skin wounds in rats. These findings suggest its potential as an emergency irrigation formulation for sodium contamination, although direct sodium removal and the independent contribution of each component require further investigation.

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PubMedSoft matter2026-08-04

Collagen type II dynamics and assembly in anisotropic porous polyacrylamide hydrogels.

Tsai Mario M, Adedeji Adediwura Deborah AD, Suresh Sneha S, Morozova Svetlana S

Inspired by liquid crystallinity and hierarchical organization in natural systems, we fabricate anisotropic polyacrylamide (PAAm) networks by templating polymerization around disodium cromoglycate (DSCG) liquid crystal phases. These anisotropic porous networks act as scaffolds that guide collagen fiber alignment, recapitulating key aspects of extracellular matrix (ECM) organization in biological tissues. The pore morphology and characteristic length scales are tuned by varying the modulus of the PAAm network, while polymerization at different temperatures induces distinct DSCG phases and corresponding pore anisotropies. Network architecture is characterized by confocal microscopy. The hydrogels are subsequently swollen in 1 mg mL-1 collagen solutions prepared in 0.012 M HCl, followed by fibril formation triggered in a neutral pH buffer. Collagen localization within the pore walls and voids is visualized, and collagen dynamics are quantified using confocal microscopy and differential dynamic microscopy (DDM), respectively. As the gel concentration increases, collagen mobility is progressively slowed and the distribution within the gel depends on the morphology and the local acrylamide concentration in pores. In networks polymerized at 30 °C, collagen localizes exclusively within the pore walls. In contrast, in gels polymerized at -20 °C collagen freely diffuses and assembles within the anisotropic pores, yielding highly aligned structures at higher collagen concentrations. Together, these results provide insight into self-assembly within crowded, elastic environments and establish a strategy for engineering biomimetic ECM scaffolds.

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PubMedInflammation and regeneration2026-08-04

Allogeneic skin transplantation induces transient fibrosis that undergoes spontaneous regression in newts.

Hosomi Kento K, Nagata Maya M, Okada Mika M, Hirano Kodai K et al.

In humans, large skin defects require tissue transplantation because adult skin lacks full regenerative capacity. However, allogeneic grafts are typically rejected due to strong immune responses, whereas autologous grafts often result in severe fibrosis and permanent scarring. In contrast, regenerative vertebrates such as newts can restore tissues with minimal scarring, suggesting the presence of distinct mechanisms regulating tissue repair. How such organisms respond to immune activation induced by non-self tissue transplantation remains unclear. In this study, we aimed to determine how adult newts respond to allogeneic skin transplantation and to examine whether fibrosis induced under such conditions is sustained or resolved. We established an allogeneic skin graft model in adult Japanese fire-bellied newts and compared it with autologous grafting. Graft fate, tissue morphology, fibrosis, and immune cell dynamics were analyzed histologically over time. To assess the contribution of macrophage-lineage cells, animals were treated with clodronate liposomes prior to transplantation. In contrast to mammals, allogeneic grafts did not exhibit typical features of acute rejection and did not show apparent graft loss. Following transplantation, grafts exhibited a characteristic sequence of changes: initial vascular integration, subsequent loss of detectable perfusion, and progressive remodeling of graft appearance. At the donor-host interface, a distinct collagen-rich fibrotic tissue formed, accompanied by marked leukocyte infiltration. This tissue appeared at 2 weeks, reached maximal thickness at 4 weeks, and regressed by 8 weeks. During this period, the graft surface gradually acquired host-like pigmentation, while structural elements of donor tissue remained detectable histologically. Iba1-positive macrophage-lineage cells accumulated within the graft during the fibrotic phase and decreased as the tissue regressed. Depletion of these cells did not prevent fibrosis formation but delayed its regression and prolonged graft thickening. Allogeneic skin transplantation in adult newts induces a distinct response in which non-self tissue is not completely lost and a collagen-rich fibrotic tissue forms transiently and subsequently undergoes resolution. These findings suggest that fibrosis induced under non-self immune activation is not necessarily a terminal state but may represent a dynamically regulated process capable of resolution.

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PubMedBone & joint research2026-08-03

Tibial cortex transverse transport accelerates diabetic wound healing via systemic mobilization of non-classical monocytes : an animal study.

Yang Yongkang Y, Jiang Zhaowei Z, Ouyang Kan K, Li Yucong Y et al.

To clarify the immunomodulatory mechanisms by which tibial cortex transverse transport (TTT) accelerates wound healing in a type 2 diabetic rat model, with particular focus on the dynamics of subsets of monocytes and macrophages. A total of 186 male Sprague-Dawley rats were induced as diabetic via a high-fat diet and streptozotocin. A full-thickness skin defect was created on the dorsum of the foot immediately following standard TTT surgery. Wound closure was monitored photographically. At defined timepoints (days 3 to 21), wound tissues underwent histological and immunofluorescence staining (haematoxylin and eosin, Masson's trichrome, picrosirius red, CD68/iNOS/mannose) to assess re-epithelialization, collagen organization, and M1/M2 macrophage populations. Flow cytometry of bone marrow and peripheral blood (CD43 and CD172a markers) quantified classical and non-classical monocyte subsets. Monocyte/macrophage involvement was probed by depleting these cells with clodronate liposomes versus phosphate-buffered saline liposomes. TTT-treated rats achieved complete wound closure by day 21, markedly faster than fixator or sham controls. Histology revealed enhanced re-epithelialization, a thicker epidermis, well-organized type III collagen, and normalized collagen fibre directionality. Immunofluorescence demonstrated a rapid decline in proinflammatory M1 and an increase in reparative M2 macrophages from day 5 onward. Flow cytometry showed a pronounced surge of non-classical monocytes in bone marrow on day 3, followed by elevated circulating levels on days 3 to 6. Monocyte/macrophage depletion markedly delayed healing and disrupted collagen deposition. TTT is associated with accelerated diabetic wound repair, accompanied by preferential mobilization of non-classical monocytes and increased M2 macrophage polarization at the wound site. These findings are consistent with a mechanically induced immunomodulatory process that may contribute to improved healing outcomes.

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Hedyotis diffusa Willd-Scutellaria barbata herbal pair suppresses triple-negative breast cancer metastasis by targeting the tumor-associated macrophage-driven OPN-CD44 signaling axis.

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Triple-negative breast cancer (TNBC) is characterized by a high propensity for metastatic relapse and a robust infiltration of tumor-associated macrophages (TAMs), which orchestrate a pro-metastatic microenvironment. Hedyotis diffusa Willd-Scutellaria barbata (HS), a classical herbal pair, exhibits potent antitumor activities; however, its specific role in modulating TAM-dependent metastasis remains unclear. This study investigated whether HS suppresses TNBC metastasis by modulating the functional state of TAMs, and sought to define the bioactive constituents and their molecular targets. The anti-metastatic activity of HS was assessed in a 4T1-luc orthotopic tumor model and a non-contact co-culture system. Macrophage depletion with clodronate liposomes was used to assess the contribution of macrophages to HS efficacy. Single-cell RNA sequencing analysis was performed to characterize macrophage-tumor cell communication. High-resolution LC-MS, molecular docking, surface plasmon resonance (SPR), and cellular thermal shift assays (CETSA) were integrated to identify HS derived constituents and validate their target engagement. HS reduced orthotopic tumor growth and distant metastatic burden in vivo. HS also reduced F4/80 positive macrophage accumulation and CD206 positive TAM associated signals in tumor tissues, and suppressed IL-4/IL-13 induced macrophage polarization in vitro. In co-culture models, HS pretreated macrophages showed a reduced ability to promote TNBC cell migration, invasion, epithelial-mesenchymal transition, and clonogenic growth. Macrophage depletion attenuated the antitumor effects of HS and apigenin (API), supporting a macrophage-dependent mechanism. Single-cell analysis identified macrophage-associated OPN and its interaction with tumor-cell CD44 as a candidate paracrine signaling axis. HS reduced macrophage OPN expression and attenuated CD44-MEK/ERK signaling in TNBC cells. API was identified as an OPN-binding constituent of HS and disrupted macrophage-derived OPN-mediated CD44-MEK/ERK activation. In vivo, API suppressed orthotopic tumor growth and reduced lung metastatic lesions. This study demonstrates that the HS herbal pair suppresses TNBC metastasis by remodeling the macrophage functional state and disrupting the signaling axis between OPN and CD44 driven by TAMs. The identification of API as an OPN binding constituent provides a mechanistic basis for further investigation of compounds derived from HS that target macrophage-tumor crosstalk in TNBC.

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Potential therapeutic targets for obstructive sleep Apnea were identified through network pharmacology, WGCNA, machine learning, immune infiltration analysis, and ceRNA network.

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