Use of a benzimidazolone compound for the preparation of a medicament for the treatment of intervertebral disc degeneration

Abstract

The application discloses application of a benzimidazolone compound in preparation of a medicine for treating intervertebral disc degeneration. 11 H 14 N4O2, and has a CAS number of 881591-33-9. The application provides an innovative treatment strategy capable of intervening in an early stage of the disease and influencing disease progression from a cause level by targeting activation of SOD1 activity which is a newly found pathogenic link of intervertebral disc degeneration.

Description

Technical Field

[0001] This invention belongs to the field of chemical drug technology, and provides the application of benzimidazole one compound in the preparation of drugs for treating intervertebral disc degeneration. Background Technology

[0002] Intervertebral disc degeneration (IVDD) is a major pathological basis for low back pain and spine-related diseases, severely impacting patients' quality of life and imposing a significant socioeconomic burden. The development of IVDD is a complex pathological process, primarily characterized by a reduction in nucleus pulposus cells and degradation of the extracellular matrix. Recent studies have shown that oxidative stress plays a central driving role in the development and progression of IVDD. Under microenvironmental stimulation such as mechanical load, inflammatory factors, or nutrient deprivation, excessive reactive oxygen species (ROS) are produced within nucleus pulposus cells, exceeding the cells' own clearance capacity. Excessive ROS accumulation not only directly damages mitochondrial function but also activates downstream apoptosis signaling pathways and the expression of matrix metalloproteinases, accelerating nucleus pulposus cell aging and apoptosis, ultimately leading to the loss of intervertebral disc structure and function. Therefore, clearing excess ROS through antioxidant strategies and restoring redox balance is considered an effective treatment approach to slow the progression of IVDD.

[0003] Superoxide dismutase 1 (SOD1), a major first-line antioxidant enzyme in cells, plays a crucial role in defending against ROS damage and maintaining the homeostasis of the intervertebral disc microenvironment. Studies have found that SOD1 expression and activity are often significantly reduced in degenerated intervertebral disc tissue, leading to the collapse of the cellular antioxidant defense system. While direct supplementation of exogenous SOD1 protein is theoretically feasible, its clinical application is greatly limited due to limitations such as short half-life, immunogenicity risks, and difficulty in penetrating the dense intervertebral disc matrix. In contrast, the search for small molecule compounds that can specifically target and enhance endogenous SOD1 activity holds promise, but their application in IVDD therapy has not yet been extensively reported.

[0004] Against this background, the present invention utilizes computer-aided drug design (CADD) technology to screen a novel small molecule compound with potential SOD1 activation activity through high-throughput virtual screening based on the active center region of SOD1. The invention also evaluates the compound's efficacy in inhibiting oxidative stress and IVDD in vivo and in vitro, and assesses its biosafety. This provides a new lead compound for the treatment of IVDD and a new theoretical basis for the development of antioxidant drugs based on structural biology. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to provide an application of benzimidazole compounds in the preparation of drugs for treating intervertebral disc degeneration, aiming to overcome the limitations of existing treatment strategies for intervertebral disc degeneration, namely, that current clinical interventions are mostly focused on symptom relief and late-stage structural repair, lacking etiological treatments targeting key pathogenic mechanisms in the early stages of the disease, and thus failing to effectively block or reverse the disease process.

[0006] To achieve the above objectives, the present invention provides the following technical solution:

[0007] This invention provides the use of a benzimidazolone compound or a pharmaceutically acceptable salt thereof in the preparation of a drug for treating intervertebral disc degeneration. The benzimidazolone compound has the Chinese name N-[(1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)methyl]urea, and the English name Urea, N-[(2,3-dihydro-1,3-dimethy-2-oxo-1H-benzimidazol-5-y)methyl]- (AC), with the molecular formula C2. 11 H 14 N4O2 has the following chemical structural formula:

[0008] .

[0009] As one of the preferred technical solutions, the benzimidazole compound or its pharmaceutically acceptable salt is used as an SOD1 agonist for the treatment of intervertebral disc degeneration.

[0010] As a further preferred technical solution, the benzimidazole compound or its pharmaceutically acceptable salt binds to the Lys123 site of the active site of SOD1, wherein the Lys123 site is the lysine residue at position 123 of the wild-type SOD1 protein as shown in SEQ ID NO.1.

[0011] As one of the preferred technical solutions, the benzimidazole compound or its pharmaceutically acceptable salt has the following effects:

[0012] (A) Activates SOD1 enzyme activity in nucleus pulposus cells;

[0013] (B) Inhibits the accumulation of superoxide anions in nucleus pulposus cells;

[0014] (C) Inhibits DNA damage and γ-H2AX accumulation in nucleus pulposus cells;

[0015] (D) Inhibits ROS accumulation in nucleus pulposus cells.

[0016] The present invention also provides the use of pharmaceutical compositions comprising benzimidazole compounds or pharmaceutically acceptable salts thereof in the preparation of medicaments for treating intervertebral disc degeneration.

[0017] The present invention also provides an intervertebral disc puncture injection, the active ingredient of which is a benzimidazole compound or a pharmaceutically acceptable salt thereof.

[0018] The beneficial effects of this invention are:

[0019] This invention provides the application of a benzimidazolone compound in the preparation of a drug for treating intervertebral disc degeneration. The benzimidazolone compound is a small molecule compound with the molecular formula C2. 11 H 14 N4O2, CAS number 881591-33-9. This invention starts from the fundamental molecular mechanism of intervertebral disc degeneration and provides an innovative treatment strategy that can intervene in the early stage of the disease and affect the progression of the disease at the etiological level by targeting and activating the newly discovered pathogenic link of SOD1 activity.

[0020] Specifically, the present invention solves the following technical problems:

[0021] 1. Screening of compounds that target and regulate SOD1 activity: Using the ChemDIV compound library and computer-aided virtual screening, compounds that can target and bind to the active site of SOD1 and regulate SOD1 activity are screened.

[0022] 2. To reveal the effects of the compound on inhibiting oxidative stress and intervertebral disc degeneration in nucleus pulposus cells, and to evaluate the therapeutic effects of the compound in in vitro cultured nucleus pulposus cells and in vivo animal models of intervertebral disc degeneration.

[0023] 3. Assess the biosafety of compound therapy for intervertebral disc degeneration by evaluating the biosafety of the compound therapy process using indicators such as blood routine tests.

[0024] This invention has the following advantages:

[0025] 1. Current treatments for intervertebral disc degeneration mostly target symptoms (pain) or late-stage structural damage, lacking targeted therapies for early molecular events. Commonly used drugs (such as NSAIDs) only relieve inflammation without altering the disease progression. This invention is the first to use SOD1 enzyme activity as a therapeutic target and intervene in the core driving factor of intervertebral disc degeneration (oxidative stress).

[0026] This invention discloses for the first time the small molecule compound C 11 H 14 The effectiveness of N4O2 as a specific SOD1 agonist provides a novel targeted solution for the treatment of intervertebral disc degeneration. Previously, there was no information regarding C... 11 H 14 Reports on N4O2 in pharmaceutical applications.

[0027] 2. Commonly used antioxidants (such as vitamins C and E) lack specificity and have limited effects; some small molecule drugs have off-target effects; systemic administration leads to adverse reactions. 11 H 14 Intradiscal injection of N4O2 demonstrates good biocompatibility, laying the foundation for its future translation. Furthermore, C... 11 H 14 N4O2 specifically activates SOD1, with a well-defined structure, small molecular weight, and stable structure; local action: intradiscal administration, minimal systemic exposure, and low systemic toxicity.

[0028] 3. The technical means employed in this invention have high specificity, high sensitivity, and repeatability, and the screened SOD1 specific activator C 11 H 14 N4O2 can serve as a potential treatment strategy for IVDD, providing a new technical direction and experimental basis for the precision diagnosis and treatment of IVDD.

[0029] Other advantages, objectives, and features of the invention will be set forth in part in the description which follows, and in part will be apparent to those skilled in the art from the following examination, or may be learned from practice of the invention. The objectives and other advantages of the invention can be realized and obtained through the following description. Attached Figure Description

[0030] To make the objectives, technical solutions, and advantages of the present invention clearer, the preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings, wherein:

[0031] Figure 1 : Schematic diagram of the high-throughput virtual screening experiment (A) and the top 10 compounds with the highest scores (B).

[0032] Figure 2 The graph shows the results of SOD1 enzyme activity detection; the bar chart with the top 10 compounds directly interfering with SOD1 enzyme activity represents SOD1 enzyme activity on the ordinate, error bars represent standard deviation, and **** indicates P < 0.001; the results show that SOD1 enzyme activity in nucleus pulposus cells decreased significantly after lactate treatment, while lactate + compound 3 (chemical formula C) 11 H 14 The SOD1 enzyme activity in the N4O2-treated group was significantly restored, confirming that C 11 H 14 N4O2 can effectively activate the SOD1 enzyme activity in nucleus pulposus cells.

[0033] Figure 3 Compound C 11 H 14 The molecular formula of N4O2 and its SOD1 molecular docking scheme.

[0034] Figure 4 Lactate and C in nucleus pulposus cells 11 H 14 The results of superoxide anion content detection after N4O2 treatment (DHE probe method) are shown in the figure. The figure includes cell imaging under a fluorescence microscope (A) and the corresponding quantitative analysis bar chart (B). In the imaging, the red fluorescence intensity represents the superoxide anion content, the vertical axis of the bar chart represents the probe fluorescence intensity, the error bar represents the standard deviation, and **** indicates P < 0.001. The results show that after lactate treatment, the red fluorescence intensity of nucleus pulposus cells is significantly enhanced, indicating an increase in superoxide anion content, while lactate + C... 11 H 14 The DHE fluorescence intensity of the N4O2-treated group was significantly reduced, confirming that C 11 H 14 N4O2 can effectively inhibit the accumulation of superoxide anions in nucleus pulposus cells.

[0035] Figure 5 Lactate and C in nucleus pulposus cells 11 H 14 The results of γ-H2AX content detection after N4O2 treatment are shown in the figure; the figure includes a cell nuclear imaging image under a fluorescence microscope (A) and the corresponding quantitative analysis bar chart (B); the red fluorescence intensity in the imaging image represents the γ-H2AX content, the vertical axis of the bar chart is the γ-H2AX fluorescence intensity, the error bar represents the standard deviation, and **** indicates P<0.001; the results show that the red fluorescence intensity of nucleus pulposus cells was significantly enhanced after lactate treatment, and the γ-H2AX content increased, while lactate + C 11 H 14 The γ-H2AX fluorescence intensity of the N4O2-treated group was significantly reduced, confirming that C 11 H 14 N4O2 can effectively inhibit DNA damage and γ-H2AX accumulation in nucleus pulposus cells.

[0036] Figure 6 Lactate and C in nucleus pulposus cells 11 H 14 The results of ROS content detection after N4O2 treatment (flow cytometry detection method) are shown in the figure. The figure includes a ROS flow cytometry plot (A) and a corresponding quantitative analysis bar chart (B). In Figure A, the vertical axis represents the ROS fluorescence intensity, and the horizontal axis represents the number of cells containing ROS fluorescence. In the bar chart of Figure B, the vertical axis represents the average fluorescence intensity of ROS, the error bar represents the standard deviation, and **** indicates P < 0.001. The results show that the ROS fluorescence intensity of nucleus pulposus cells is significantly enhanced after lactate treatment, while lactate + C 11 H 14 The ROS fluorescence intensity of the N4O2-treated group was significantly reduced, confirming that C 11 H 14 N4O2 can effectively inhibit the accumulation of ROS in nucleus pulposus cells.

[0037] Figure 7 Rats in sham-operated group, PIDD group and C 11 H 14 SO & FG staining images of the PIDD group treated with N4O2; the images include SO & FG staining images of intervertebral disc tissue (A) and corresponding histological score bar charts (B); the vertical axis of the bar chart represents the histological score, the error bar represents the standard deviation, and **** indicates P<0.001; the results show that after acupuncture modeling treatment, the nucleus pulposus tissue was significantly reduced, the intervertebral height was significantly decreased, the histological score was significantly increased, and the intervertebral disc degeneration was obvious, while C 11 H 14 The degree of intervertebral disc degeneration in the N4O2 treatment group was similar to that in the C 11 H 14 The concentration of N4O2 is inversely proportional to the concentration of C, confirming that in a rat acupuncture degeneration model, C 11 H 14 N4O2 treatment can effectively inhibit intervertebral disc degeneration. Scale bar = 500μm.

[0038] Figure 8 :C 11 H 14 Biocompatibility of N4O2 in treating intervertebral disc degeneration; error bars represent standard deviation, ns represents no significant change; (AE) Received different concentrations of C 11 H 14 Organ index values ​​in the N4O2 intradiscal injection group (n = 6 rats); (FK) differences in major blood routine indicators (RBC: red blood cells; WBC: white blood cells; PLT: platelets; HGB: hemoglobin; MCV: mean corpuscular volume; MCH: mean corpuscular hemoglobin) (n = 6 rats individually); (LM) liver function indices (ALT: alanine aminotransferase; AST: aspartate aminotransferase) (n = 6 rats). Detailed Implementation

[0039] The present invention will be further described below with reference to specific embodiments. The accompanying drawings are for illustrative purposes only, representing schematic diagrams rather than actual physical objects, and should not be construed as limiting the scope of this patent. To better illustrate the embodiments of the present invention, some components in the drawings may be omitted, enlarged, or reduced, and do not represent the actual dimensions of the product. It is understandable to those skilled in the art that some well-known structures and their descriptions may be omitted in the drawings.

[0040] I. Preparation of Experimental Materials

[0041] 1. Cells: Rat nucleus pulposus cells were extracted from the caudal intervertebral discs of SD rats using the method described in the applicant's reference "Isolation, Culture and Identification of Rat Caudal Intervertebral Disc Nucleus Pulsus Cells, 2016, 35, (1-6)". The cells were cultured in DMEM / F12 medium containing 10% fetal bovine serum (FBS, Gibco brand) and 1% penicillin-streptomycin mixture (solarbio brand) and were routinely cultured in a 37℃, 5% CO2 incubator. Cells in the logarithmic growth phase were selected for subsequent experiments.

[0042] 2. Tissue Sample Source: Thirty healthy SPF-grade male SD rats (8 weeks old, weighing 200-220g) were purchased from Chengdu Dashuo Experimental Animal Technology Co., Ltd. The rats were randomly divided into 5 groups: sham-operated group, PBS group, low-dose C group, and [other groups not specified in the original text]. 11 H 14 N4O2 group, medium dose C 11 H 14 N4O2 group, high-dose C 11 H 14 The N4O2 group consisted of 6 rats per group. After effective anesthesia, the rats in the model group were fixed in a prone position. The intervertebral disc at the 6th-7th segment of the caudal vertebrae was located, and a sterile 21G needle was used to vertically puncture the center of the intervertebral disc to a depth of 5 mm. After 30 seconds, the needle was slowly withdrawn to establish a rat caudal intervertebral disc degeneration model. Subsequently, PBS (0.01M, pH=7.4) and C were injected using a 26-gauge needle and a micro-syringe, respectively. 11 H 14 N4O2 (5μM, 25μM, 50μM) was applied to the intervertebral disc between the 6th and 7th vertebrae of the caudal vertebrae. All rats were routinely housed for 4 weeks post-surgery at an ambient temperature of 22-25℃ and humidity of 50%-60%, with free access to food and water. After 4 weeks, the rats were anesthetized again, and the intervertebral disc between the 6th and 7th vertebrae of the caudal vertebrae was dissected and separated. This experimental protocol was approved by the Laboratory Animal Ethics Committee of our institution (Ethics Approval No.: AMUWEC20235167), and the experimental process strictly adhered to animal welfare and ethical guidelines.

[0043] 3. Main reagents and instruments: C 11 H 14N4O2 compound (MedChemExpress); trypsin (Promega brand); SOD enzyme activity assay kit, total antioxidant capacity (T-AOC) assay kit, superoxide anion assay kit (DHE probe method, all purchased from Beyotime), modified SO2 & FG staining kit (Solarbio, catalog number G1371). Inverted microscope (Olympus CKX53), Gallios flow cytometer (Beckman), molecular dynamics simulation: software: Gromacs2018.4, force field: Amber14SB, water model: TIP3P; virtual screening platform: software: Schrödinger Maestro11.4, module: Glide (HTVS / SP / XP).

[0044] II. Specific Implementation Steps

[0045] 1. Establishment of cell model

[0046] 1.1: Isolation of primary nucleus pulposus cells: Rat caudal nucleus pulposus tissue was obtained, digested with 0.2% type II collagenase at 37°C for 2 hours, centrifuged at 400×g for 5 minutes, and cultured with DMEM / F12 + 10% FBS + 1% double antibiotics.

[0047] 1.2 Lactic acid treatment model: When cells were passaged to the second generation, the culture medium was changed to one containing lactate (2mM, 6mM, 10mM), and the medium was changed every 3 days for 7 days. The control group was treated with normal culture medium.

[0048] 2. High-throughput virtual screening

[0049] 2.1 Protein Structure Preparation: The crystal structure of human SOD1 protein (PDB ID: 1PU0) was obtained from the RCSB Protein Data Bank. The electrostatic loop region (residues 122–144, conserved between humans and rats) containing lysine 123 (Lys123) at the active site was selected. This region is involved in guiding superoxide anion (O2) ions... - The protein structure was transferred to the SOD1 active site (copper ion binding site). The Protein Preparation Wizard module of the Schrödinger Maestro software was used to perform hydrogen atom addition, charge distribution, water molecule removal, and energy minimization to obtain an optimized structure suitable for molecular docking.

[0050] 2.2: Compound library screening: ChemDIV compound library (1.6 million small molecules); the LigPrep module of Schrödinger was used to optimize the structure of the compounds, including: generating possible three-dimensional conformations; optimizing hydrogen bond networks; predicting ionization states (pH 7.0±2.0); assigning appropriate charges (OPLS4 force field); removing repetitive structures; and retaining compounds with good drug-like properties and structural diversity for subsequent virtual screening.

[0051] 2.3: Three-level molecular docking screening ( Figure 1 (A)

[0052] 2.3.1 Preliminary screening: The Glide module was used to perform preliminary docking on all pretreated compounds, and the 10% of compounds with the strongest binding ability to the Lys123 site of the SOD1 active site were screened out.

[0053] 2.3.2 Standard Precision Screening: The compounds obtained from the initial screening were subjected to Glide Standard Precision docking to further evaluate binding affinity and conformational stability, and the top 10% of compounds were selected to proceed to the next round.

[0054] 2.3.3 High-precision screening: The remaining compounds were finely docked using the Glide Extra Precision mode to evaluate key parameters such as binding free energy, hydrogen bond network, and hydrophobic interactions.

[0055] 2.3.4 Result Ranking and Candidate Compound Selection: The compounds were ranked according to the GlideScore (binding energy score), and the top 10 compounds with the highest scores were selected as potential activator candidates. Figure 1 (B)

[0056] 3.3 Verification of SOD1 Enzyme Activity Recovery: An SOD1 activity assay kit was used to detect whether the catalytic activity of SOD1 in NPCs was restored after compound treatment. Cell lysis and quantification were performed using the BCA method. SOD activity assay kit procedure: WST-8 working solution was added, followed by enzyme working solution, incubation at 37°C for 30 minutes, and absorbance was measured at 450 nm. Results: Compound No. 3, chemical formula C... 11 H 14 N4O2 restores SOD1 activity to 80% of normal levels. Figure 2 ).

[0057] 3.4. Analysis of binding modes: Thr40, His44, Lys123, and Asn140 are key binding residues ( Figure 3 ).

[0058] 3. Cellular experiments to verify C 11 H14 N4O2 effect

[0059] 3.1 Cell model construction: Rat nucleus pulposus cells (NPCs) were used as an in vitro model, and SOD1 oxidative stress injury was induced by lactate treatment.

[0060] 3.4 Detection of Oxidative Stress Indicators: ROS Detection: Total ROS detection kit, flow cytometry analysis; O2 - Detection: Dihydroethidium (DHE) fluorescence staining (10 μM DHE, incubated at 37°C in the dark for 30 minutes), observation by confocal microscopy and quantification by fluorescence spectrophotometer; Results: C 11 H 14 N4O2 reduces ROS by 50-60%.

[0061] 3.5 Cell damage assessment: DNA damage: γ-H2AX immunofluorescence staining, positive cell count; Cell senescence: β-galactosidase staining, positive rate calculation; Results: C 11 H 14 N4O2 reduces the expression of DNA damage and cellular senescence markers.

[0062] 4. In vivo experimental verification of C 11 H 14 N4O2 effect ( Figure 7 )

[0063] 7.1 PIDD model: Male SD rats (2 months old, 200-220g) were anesthetized with isoflurane inhalation. The caudal vertebral intervertebral space 5-6 was located (by palpation or X-ray). A 21G needle (with a depth limiter) was vertically inserted to a depth of 5mm, rotated 360°, and held for 30 seconds. Postoperative disinfection and analgesic antibiotic treatment were administered for 3 days.

[0064] 7.2: Grouping and Treatment: Control group: sham surgery (acupuncture only); Model group: PIDD + PBS injection; Treatment group 1: PIDD + low-dose vitamin C 11 H 14 N4O2 injection (5μM), Treatment group 2: PIDD + medium-dose C 11 H 14 N4O2 injection (25μM), Treatment group 3: PIDD + high-dose C 11 H 14 N4O2 injection (50μM).

[0065] 7.3 Administration regimen: Direct injection: After model establishment, C was injected into the puncture site using a 26G needle and a Hamilton microsyringe. 11 H 14 N4O2, administration frequency: once a week for 4 consecutive weeks.

[0066] 7.4 Evaluation of Treatment Efficacy:

[0067] Histological evaluation: Animals were euthanized, intervertebral disc tissue was obtained, fixed in 4% paraformaldehyde for 48 hours, decalcified with EDTA for 2 weeks, embedded in paraffin, sectioned at 5 μm, stained with modified SO & FG, and histologically scored by three researchers in a blinded manner.

[0068] Results: The treatment group showed a 30-50% improvement in the three-point score.

[0069] 8. Biosafety assessment ( Figure 8 )

[0070] 8.1 In vivo safety:

[0071] Continuous drug administration monitoring: The therapeutic dose (50 μM) was injected weekly for 4 consecutive weeks, and body weight and food intake were monitored. Results: Steady weight gain with no abnormalities; Hematological tests: Blood was collected 24 hours after the last administration, and a complete blood count was performed using a fully automated hematology analyzer; liver function was measured using a biochemical analyzer.

[0072] Results: All indicators were within the normal range. Histopathology: Heart, liver, spleen, lung, and kidney samples were taken, fixed in 4% paraformaldehyde, sectioned in paraffin, stained with hematoxylin and eosin (HE), and evaluated by a blinded pathologist. Results: No pathological changes were found in the major organs, and no inflammation or necrosis was observed at the injection site.

[0073] Summary of Experimental Results

[0074] This implementation scheme successfully identified the small molecule compound C through the above series of experiments. 11 H 14 N4O2 specifically activates SOD1 activity, enhancing the total antioxidant capacity of nucleus pulposus cells and inhibiting superoxide anion accumulation, thereby reducing oxidative stress damage to nucleus pulposus cells and effectively alleviating the pathological process of IVDD. The experimental procedures in this implementation scheme are clear and highly reproducible. The attached figures visually verify the core conclusions of this invention, providing a reliable experimental basis for the development of subsequent IVDD treatment strategies.

[0075] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. The use of a benzimidazolone compound or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating intervertebral disc degeneration, characterized in that, The Chinese name of this benzimidazolone compound is N-[(1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)methyl]urea, and its molecular formula is C2. 11 H 14 N4O2 has the following chemical structural formula: 。 2. The use of a pharmaceutical composition comprising a benzimidazolone compound or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating intervertebral disc degeneration, characterized in that, The Chinese name of this benzimidazolone compound is N-[(1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)methyl]urea, and its molecular formula is C2. 11 H 14 N4O2 has the following chemical structural formula: 。 3. A disc puncture injection agent, characterized in that, Its active ingredient is the benzimidazolone compound of claim 1 or a pharmaceutically acceptable salt thereof. The Chinese name of the benzimidazolone compound is N-[(1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)methyl]urea, and its molecular formula is C1. 11 H 14 N4O2 has the following chemical structural formula: 。

Images