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Composition for treating osteomyelitis and application thereof

A composition and osteomyelitis technology, applied in the field of medicine, can solve the problems of affected joints, re-infection, and infected limbs, and achieve the effect of restoring bactericidal ability, killing pathogens, and reducing the recurrence of infection

Pending Publication Date: 2021-11-26
NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Disadvantages of Existing Technology: For osteomyelitis, current treatment options are surgical excision of infected tissue and stringent antibiotic therapy to minimize bacterial load
However, due to the enhanced resistance of bacteria embedded in biofilms to most antibiotics, the decrease of host innate immunity caused by S.aureus infection, and the presence of dormant bacteria in biofilms, bone niches and / or host cells, treatment methods Often incomplete clearance of pathogen and reinfection frequently occurs
Ultimately, this can lead to non-union bone defects, stiffness in the affected joints and even amputation of infected limbs

Method used

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  • Composition for treating osteomyelitis and application thereof
  • Composition for treating osteomyelitis and application thereof
  • Composition for treating osteomyelitis and application thereof

Examples

Experimental program
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Embodiment 1

[0052] A mouse model of S.aureus infectious osteomyelitis was made, and mice were treated with gentamicin (4mg / ml, 0.1ml, intraperitoneal injection, once a day) on the first day after surgery, combined with PD-1 or PD - Mice in the L1 neutralizing antibody treatment group were given PD-1 neutralizing antibody (Anti-PD-1Ab, #BE0146, Bio X Cell, NH, USA) (200 μg / mouse, once every 3 days) on the 5th day after operation ) or PD-L1 neutralizing antibody (Anti-PD-L1 Ab, #BE0101, Bio X Cell, NH, USA) (200μg / mouse, once every 3 days), while the mice in the non-treatment group were injected with isotype control Antibody (Isotype control antibody, #BE0083, Bio X Cell, NH, USA) (200 μg / monkey, once every 3 days), and bone tissue samples on the side of the operation were collected on the 14th day after operation. The soft tissue attached to the bone tissue was removed, the implanted nail was taken out, the bone tissue was weighed and crushed, and PBS solution was added at a ratio of 10 μL...

Embodiment 2

[0055] Raw264.7 mouse macrophage cell line was cultured at 1×10 5 CFU / cm 2 Inoculate a 6-well plate at a density, infect cells with S.aureus at an MOI of 10 (ratio of bacterial CFU to cell number) and treat with neutralizing antibodies to PD-1 (10 μg / mL) or PD-L1 (10 μg / mL) , and the control group was treated with an equal volume of isotype control antibody. After 1 hour, 20 μg / mL lysostaphin and 50 μg / mL gentamicin were used to incubate at 37°C to remove extracellular bacteria. Rinse the cells with sterile PBS solution twice, then lyse the cells, and dilute the cell lysate in gradients, the dilution times are 1×, 10×, 100×, 500×, 1000×, 2000×, see Figure 7 , spread agar plate culture, and calculate the bacterial load in each cell to reflect the phagocytosis. In order to study the effect of neutralizing antibodies against PD-1 or PD-L1 on the bactericidal ability of cells, continue to culture in growth medium and treat with neutralizing antibodies against PD-1 or PD-L1 for...

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Abstract

The invention discloses a composition for treating osteomyelitis and application thereof. The composition for treating osteomyelitis consists of antibiotics and a PD-1 / PD-L1 inhibitor. According to the findings of the invention, a PD-L1 / PD-1 neutralizing antibody drug can assist the antibiotics in the treatment of acute and chronic infectious osteomyelitis. Starting with activation of innate immunity, the PD-L1 / PD-1 neutralizing antibody is applied for partially relieving the innate immune inhibition state in acute and chronic infectious osteomyelitis to recover sterilization capability of macrophages, thereby assisting the antibiotics to achieve better pathogen killing effect to reduce infection recurrence and improve bone healing.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a composition for treating osteomyelitis and its application. Background technique [0002] Infectious osteomyelitis is an inflammation of bone and bone marrow caused by pathogenic bacteria, characterized by severe local inflammation and progressive bone destruction, and is often secondary to infection caused by open trauma of long bones or internal fixation of fractures. In recent years, the incidence of trauma and fractures caused by traffic accidents and falls has continued to increase, and the number of patients with infectious osteomyelitis has increased year by year. Infectious osteomyelitis has always been a difficult problem in orthopedic clinical treatment at home and abroad. The conventional treatment options such as thorough debridement, systemic and local antibiotics usually have limited curative effect, and the infection is often protracted and has a high recurrence...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K39/395A61K31/7036A61K31/7088A61P31/04A61P19/08A61P7/00
CPCA61K45/06A61K39/3955A61K31/7036A61K31/7088A61P31/04A61P19/08A61P7/00A61K2300/00
Inventor 余斌张先荣李凯群陈昱辉
Owner NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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