CN-122005569-A - Application of lurasidone or pharmaceutically acceptable salt thereof in preparation of drugs for preventing and/or treating bone injury healing disorder of diabetic individual

Abstract

The invention provides application of lurasidone or pharmaceutically acceptable salt thereof in preparing a medicament for preventing and/or treating bone injury healing disorder of a diabetic individual. The hyperglycemic environment results in excessive secretion of lipocalin-2 (LCN 2) by activating the pentose phosphate pathway of neutrophils, thereby inhibiting osteogenic differentiation of skeletal stem cells. The lurasidone or the pharmaceutically acceptable salt thereof provided by the invention is applied to the preparation of a medicament for preventing and/or treating the bone injury healing disorder of a diabetic individual, and in the application provided by the invention, the lurasidone can specifically inhibit the metabolic pathway and the secretion of LCN2, remodel the immune microenvironment which is favorable for repairing, obviously accelerate poroma formation under the condition of diabetes and improve the bone mineral density.

Inventors

• SHI JUNYU
• CHEN RUIYING
• LAI HONGCHANG
• ZHANG XIAOMENG
• LV XIAOLEI
• DING XINXIN

Assignees

• 上海交通大学医学院附属第九人民医院

Dates

Publication Date

20260512

Application Date

20260331

Claims (7)

1. 1. Use of lurasidone or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the prevention and/or treatment of a bone injury healing disorder in a diabetic individual.
2. 2. The use according to claim 1, wherein the diabetic individual has a bone injury healing disorder comprising delayed healing of fractures in diabetic and hyperglycemic environments, bone nonunion, pseudoarthroplasty, poor repair of bone defects, osteoporotic fractures, and bone regeneration disorders following orthopedic surgery.
3. 3. The use according to claim 1, wherein the medicament has the use of promoting healing of bone lesions by improving the local immune microenvironment of lesions in diabetic individuals.
4. 4. Use according to claim 3, characterized in that said improving the immune microenvironment, in particular modulating the function of neutrophils, comprises: inhibit the metabolic activity of pentose phosphate pathway in neutrophils, And/or the number of the groups of groups, Inhibit the secretion of lipocalin-2 in neutrophils.
5. 5. A pharmaceutical composition for promoting fracture healing in diabetic environments, comprising lurasidone or a pharmaceutically acceptable salt thereof according to any one of claims 1-4, and a pharmaceutically acceptable carrier.
6. 6. A bone repair material for promoting fracture healing in a diabetic environment, comprising a biocompatible scaffold and lurasidone or a pharmaceutically acceptable salt thereof supported on the scaffold.
7. 7. The bone repair material of claim 6, wherein the biocompatible scaffold is selected from at least one of a hydrogel, bone cement, collagen sponge, nanofiber scaffold, microsphere, or 3D printed bone scaffold.

Description

Application of lurasidone or pharmaceutically acceptable salt thereof in preparation of drugs for preventing and/or treating bone injury healing disorder of diabetic individual Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to application of lurasidone or pharmaceutically acceptable salts thereof in preparation of medicines for preventing and/or treating bone injury healing disorder of diabetic individuals. Background Diabetes is a chronic metabolic disease characterized by hyperglycemia and impaired insulin levels or function, and is also one of the major health challenges facing the world in the 21 st century. Epidemiological data indicate that about 5.89 million adults worldwide are affected by this pathology in 2024, and that it is expected that the number of ill persons will reach 8.53 million in 2050. Clinical studies show that the fracture incidence rate of diabetics is obviously higher than that of healthy people, and the fracture healing process is often accompanied by obvious delay or damage, so that serious consequences such as bone nonunion, malformation healing and the like are extremely easy to cause, thereby not only increasing the disability rate of the patients, but also bringing heavy burden to medical systems. Fracture healing is a complex and delicate biological process involving a high degree of coordination of various cells, particularly immune cells. The process begins at the moment of injury, with neutrophils acting as a "pioneer" for innate immunity, rapidly infiltrating into the hematoma area within hours after fracture. They not only clear necrotic tissue and pathogens, but more importantly recruit monocytes/macrophages to the site of injury by secreting cytokines such as interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and stromal cell derived factor-1 alpha (SDF-1 alpha/CXCL 12), thereby initiating a repair cascade. Subsequently, macrophages switch locally from a pro-inflammatory M1 phenotype to an anti-inflammatory/reparative M2 phenotype at the lesion, releasing TGF- β, VEGF, IGF-1 and other factors, directly regulating bone stem cell/mesenchymal stem cell osteogenic differentiation and vascularization. It can be said that initiating inflammation from the neutral granulocytes, phenotype transformation of macrophages, and driving stem cell osteogenesis by immune factors, a cascade of sequential participation of immune cells is an integral part of bone regeneration. However, in diabetic pathological conditions, the delicate "immune-skeletal" dialogue described above is deeply and extensively disrupted. The persistent hyperglycemic environment directly compromises the initiation of the immune response-i.e., the function of neutrophils, including their ability to chemotaxis, phagocytose and form extracellular traps. At the same time, metabolic disorders (e.g., accumulation of advanced glycation end products) hinder the functional phenotype of neutrophils and macrophages, allowing them to remain in a pro-inflammatory state for a long period of time, resulting in local formation of chronic, non-regressive low-inflammatory microenvironments in the lesion. This toxic microenvironment severely inhibits the osteogenic activity and survival of skeletal stem cells, and severely impairs the formation of new blood vessels that provide nutrition for repair. At present, the prior art schemes aiming at the diabetic fracture healing disorder mainly comprise the following categories, but certain limitations exist: Blood glucose control and basal therapy, intensive insulin therapy, while being a management matrix, improves metabolic environment and partially promotes bone healing, often relies on patient long-term compliance and has difficulty in completely reversing the localized microenvironment lesions that have formed with limited effectiveness for the healing disorder that has occurred. Surgical and biological material interventions such as bone grafting, bone cement filling, biological scaffolds, and the like. These methods mainly provide mechanical support or passive filling, while attempting to provide a physical framework for bone regeneration, in cases of severe immune microenvironment, insufficient blood supply, caused by diabetes, the integration rate of the implant material is low and high risk of infection is encountered. The medicine therapy comprises the use of bisphosphonates, teriparatide and other anti-osteoporosis medicines. These drugs are not specifically designed for diabetic fractures, bisphosphonates may excessively inhibit bone remodeling, whereas teriparatide stimulates bone formation but fails to address the upstream immunomodulation problem. Recently emerging growth factor patches for soft tissue healing and the like, applications in bone repair remain to be explored further. Local cytokine therapy, such as the use of Platelet Rich Plasma (PRP) or Bone Morphogenic Proteins (BMPs). Such strate