Use of serine in the preparation of a medicament for preventing or treating intervertebral disc degeneration

Abstract

The application discloses application of serine or a pharmaceutically acceptable salt thereof in preparation of a medicine for preventing or treating intervertebral disc degeneration, and a medicine composition containing the active ingredient, and belongs to the technical field of biological medicine. The application takes serine as the active ingredient, provides application of the serine in preparation of the medicine for treating intervertebral disc degeneration, the medicine can supplement serine exogenously, corrects redox imbalance of nucleus pulposus cells, reverses cell aging, and thus can improve the intervertebral disc degeneration process. The application further provides a corresponding medicine composition, which can be prepared into a local injection preparation or an oral preparation, wherein the local injection preparation can be combined with a biomaterial to construct a slow-release delivery system, so that long-acting targeted drug delivery is achieved.

Description

Technical Field

[0001] This application relates to the field of biomedical technology, and in particular to the use of a serine or a pharmaceutically acceptable salt thereof in the preparation of a drug for the prevention or treatment of intervertebral disc degeneration. Background Technology

[0002] Intervertebral disc degeneration (IVDD) is a common degenerative disease of the spine in clinical practice. Its pathogenesis is complex and is closely related to the aging of nucleus pulposus cells, imbalance between the synthesis and degradation of extracellular matrix, and abnormal redox stress response. With the increasing aging of the population and the prevalence of unhealthy lifestyle habits such as prolonged sitting and overuse, the incidence of IVDD is rising year by year. It can cause symptoms such as low back pain, radiating pain in the lower limbs, and neurological dysfunction, seriously reducing patients' quality of life and placing a huge burden on the medical system.

[0003] Currently, treatment options for IVDD mainly include conservative treatment (such as analgesics and physical therapy) and surgical treatment (such as discectomy and spinal fusion). Conservative treatment can only relieve symptoms and cannot reverse the pathological process of disc degeneration; while surgical treatment can relieve nerve compression, it has problems such as large trauma, high risk of postoperative complications, and accelerated degeneration of adjacent intervertebral discs after fusion.

[0004] Therefore, developing novel therapeutic drugs that can reverse the aging of nucleus pulposus cells and correct redox imbalance is of great clinical significance and social value for the precise and non-invasive treatment of IVDD. Summary of the Invention

[0005] This invention aims to address the shortcomings of existing treatments for intervertebral disc degeneration, which can only relieve symptoms but cannot reverse the pathological process, and surgical treatment is highly invasive and has many complications. It provides a new serine-based approach for the prevention or treatment of intervertebral disc degeneration, which reverses the aging of nucleus pulposus cells and corrects the redox imbalance through a clear mechanism of action, providing a new drug option for the treatment of IVDD.

[0006] The technical solution provided by this invention is as follows: In one aspect, this application provides the use of serine or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the prevention or treatment of intervertebral disc degeneration.

[0007] In some embodiments, the serine includes L-serine.

[0008] In some embodiments, the drug includes at least one of a locally injectable formulation and an oral formulation.

[0009] In some embodiments, the locally injectable formulation is an intradiscal injection formulation selected from at least one of aqueous solutions, suspensions, in-situ hydrogels, and sustained-release microspheres.

[0010] In some embodiments, the locally injectable formulation comprises a locally sustained-release delivery system made of biomaterials.

[0011] In some embodiments, the intervertebral disc degeneration is accompanied by nucleus pulposus cell senescence and / or intracellular redox imbalance.

[0012] Secondly, this application provides a pharmaceutical composition for the prevention or treatment of intervertebral disc degeneration, wherein the pharmaceutical composition has serine or a pharmaceutically acceptable salt thereof as the active ingredient and contains pharmaceutically acceptable excipients or biological sustained-release carriers.

[0013] In some embodiments, the pharmaceutical composition is configured to be administered via local intradiscal injection.

[0014] Thirdly, this application provides a kit for treating intervertebral disc degeneration, comprising the pharmaceutical composition and injection device described above.

[0015] Compared with existing technologies, the beneficial effects of this application are: (1) Target-specific, reversing aging from the root of metabolism: Based on the novel RFBOX2-PHGDH-SSP axis pathogenesis mechanism, this application directly supplements the downstream key metabolite serine, achieving precise repair of damaged redox balance, and has the potential to promote aging reversal through disease modification therapy.

[0016] (2) Excellent drug-like properties and high safety: Serine, as a naturally occurring non-essential amino acid in the human body, has extremely high biocompatibility and safety, with no obvious toxic side effects. Compared with complex gene therapy or macromolecular protein drugs, serine is inexpensive, stable, and easy to industrialize and process.

[0017] (3) Significant therapeutic effect: In animal models, local supplementation with serine can significantly restore the vitality of intervertebral disc cells and matrix synthesis, showing great potential for clinical translation. Attached Figure Description

[0018] To more clearly illustrate the technical solutions in the embodiments of this application, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0019] Figure 1 A schematic diagram illustrating the molecular mechanism by which exogenous serine supplementation targets and regulates the SSP pathway and reverses nucleus pulposus cell senescence, as provided in the embodiments of this application.

[0020] Figure 2This is a graph showing the effect of serine intervention in Example 1 of this application on the improvement of GSH / ROS redox balance and aging phenotype (SA-β-gal staining) of senescent nucleus pulposus cells in vitro (* indicates P<0.05; **** indicates P<0.0001).

[0021] Figure 3 The images are comparative images of rat intervertebral disc degeneration model after local injection of serine in Example 2 of this application (* indicates P<0.05; ** indicates P<0.01; **** indicates P<0.0001; ns indicates no statistical difference).

[0022] Figure 4 The image shows a comparison of pathological staining and degeneration scores of rat intervertebral disc tissue in Example 2 of this application (** indicates P<0.01; *** indicates P<0.001; **** indicates P<0.0001; ns indicates no statistical difference). Detailed Implementation

[0023] To make the objectives, technical solutions, and advantages of this application clearer, the technical solutions of this application will be clearly and completely described below in conjunction with the embodiments of this application. Obviously, the described embodiments are only some, not all, of the embodiments of this application. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0024] Intervertebral disc degeneration (IVDD) is a major cause of low back pain and related degenerative spinal diseases. As the disease progresses, its most prominent pathological feature is the extensive senescence of nucleus pulposus cells (NPCs). Currently, clinical treatments for IVDD primarily focus on symptom relief, such as conservative treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics, or surgical interventions like spinal fusion in the later stages of the disease. In the area of ​​potential drug development targeting the underlying cause, existing research strategies largely focus on anti-inflammatory effects or stimulating cell proliferation through growth factors to improve the condition.

[0025] However, current clinical treatments cannot reverse the pathological process of intervertebral disc degeneration, and there is currently a lack of effective targeted drugs for the fundamental cause of nucleus pulposus cell senescence.

[0026] The applicant's research found that during intervertebral disc degeneration, the expression level of RNA-binding protein RBFOX2 (Fox-1 homolog 2) is significantly downregulated, which in turn inhibits the expression of PHGDH, a key rate-limiting enzyme in the serine synthesis pathway (SSP). This ultimately leads to the depletion of intracellular serine and glycine levels, a decrease in glutathione (GSH) synthesis, and further exacerbation of intracellular redox imbalance, ultimately driving senescence in nucleus pulposus cells.

[0027] In view of this, the present invention aims to address the technical shortcomings of existing treatments for intervertebral disc degeneration, which can only relieve symptoms and cannot reverse the pathological process, and surgical treatment is highly invasive and has many complications. It provides a new serine-based approach for the prevention or treatment of intervertebral disc degeneration, which reverses the aging of nucleus pulposus cells and corrects the redox imbalance through a clear mechanism of action, providing a new drug option for the treatment of IVDD.

[0028] In one aspect, this application provides the use of serine or a pharmaceutically acceptable salt thereof in the preparation of a medicament for the prevention or treatment of intervertebral disc degeneration.

[0029] In some embodiments provided in this application, the serine includes L-serine. L-serine, as a naturally occurring active form, has higher bioavailability and activity, and can more effectively prevent or treat intervertebral disc degeneration.

[0030] In some embodiments provided in this application, the drug corrects the redox imbalance in nucleus pulposus cells and reverses cell senescence by exogenously supplementing serine. Specifically, this invention discloses that impaired endogenous serine synthesis pathway is one of the key inducing factors leading to redox imbalance and cell senescence in nucleus pulposus cells. During intervertebral disc degeneration, the expression of RNA-binding protein RBFOX2 is downregulated, inhibiting the expression of PHGDH, a key rate-limiting enzyme in the serine synthesis pathway (SSP), resulting in a decrease in intracellular serine levels, impaired glutathione (GSH) synthesis, and exacerbation of redox imbalance, ultimately driving nucleus pulposus cell senescence.

[0031] Based on the above mechanism, see Figure 1 This application addresses the issue of serine deficiency by directly bypassing the endogenous serine synthesis pathway by supplementing serine exogenously, restoring serine levels in nucleus pulposus cells, and activating glutathione synthesis. This corrects redox imbalance and reverses the aging phenotype of nucleus pulposus cells. This strategy can enhance the antioxidant capacity of nucleus pulposus cells from a metabolic perspective, delaying or even reversing the pathological process of intervertebral disc degeneration.

[0032] In some embodiments provided in this application, the drug includes at least one of a locally injectable formulation and an oral formulation. Different administration methods can be adapted to different clinical scenarios. Local injection can achieve targeted drug delivery and reduce systemic adverse reactions; oral formulations are convenient to take and suitable for long-term management of patients with mild symptoms. The appropriate dosage form can be selected according to the patient's actual condition.

[0033] In some embodiments provided in this application, the locally injected formulation is an intradiscal injection formulation selected from at least one of aqueous solution, suspension, in-situ hydrogel, and sustained-release microspheres. These formulations can be directly injected into the diseased intervertebral disc, precisely targeting the nucleus pulposus cells, increasing local drug concentration, enhancing therapeutic efficacy, and simultaneously reducing the impact of the drug on surrounding normal tissues.

[0034] In some embodiments provided in this application, the locally injected formulation comprises a locally sustained-release delivery system made of biomaterials. This sustained-release delivery system can prolong the residence time of the drug in the intervertebral disc, achieving continuous and stable release of serine, avoiding frequent dosing, improving patient medication compliance, and simultaneously maintaining stable blood and local tissue drug concentrations, ensuring the continuity of therapeutic effects.

[0035] In some embodiments provided in this application, the intervertebral disc degeneration is accompanied by nucleus pulposus cell senescence and / or intracellular redox imbalance. The drug application of this invention achieves precise treatment of IVDD by targeting and regulating the senescence and redox state of nucleus pulposus cells, and is suitable for patients with intervertebral disc degeneration accompanied by the above-mentioned pathological characteristics.

[0036] Secondly, the present invention also provides a pharmaceutical composition for the prevention or treatment of intervertebral disc degeneration, the pharmaceutical composition having serine or a pharmaceutically acceptable salt thereof as the active ingredient, and comprising pharmaceutically acceptable excipients or biological sustained-release carriers.

[0037] In some embodiments provided in this application, the pharmaceutical composition is configured for administration via local intradiscal injection. Local injection delivers the active ingredient directly to the lesion site, avoiding drug concentration dilution due to systemic metabolism and improving treatment efficiency.

[0038] Thirdly, the present invention also provides a kit for treating intervertebral disc degeneration, the kit comprising the pharmaceutical composition and injection device as described in the second aspect.

[0039] This invention's kit combines a pharmaceutical composition containing serine or its pharmaceutically acceptable salts with a dedicated injection device. It retains the core therapeutic mechanisms of exogenous serine supplementation, bypassing endogenous synthesis barriers, restoring serine levels in nucleus pulposus cells, activating glutathione synthesis, correcting redox imbalance, and reversing nucleus pulposus cell senescence. Furthermore, the compatible injection device enables precise intradiscal targeted drug delivery. It allows for flexible selection of various sustained-release delivery methods, such as aqueous solutions, in-situ hydrogels, and sustained-release microspheres, extending the drug's residence time and duration of action within the intervertebral disc, reducing the frequency of administration and the risk of systemic adverse reactions. This significantly improves the targeting, effectiveness, and patient compliance of intervertebral disc degeneration treatment, providing a convenient and standardized integrated tool for precise and long-term clinical treatment of intervertebral disc degeneration.

[0040] The present invention will be further described in detail below with reference to the embodiments and accompanying drawings, but the embodiments of the present invention are not limited thereto.

[0041] Unless otherwise specified, the experimental materials used in the examples and comparative examples were prepared according to the following methods or purchased from conventional commercial channels: Primary nucleus pulposus cells: Human NP tissue was obtained from 8 patients with thoracic and lumbar vertebral fractures, scoliosis, or lumbar disc herniation who underwent spinal surgery. The extraction method is described in the literature Liang H, Luo R, Li G, Zhang W, Zhu D, Wu D, Zhou X, Tong B, Wang B, Feng X, Wang K, Song Y, Yang C. Lysine methylation of PPP1CA by the methyltransferase SUV39H2 disrupts TFEB-dependent autophagy and promotes intervertebral disc degeneration. Cell Death Differ. 2023 Sep;30(9):2135-2150. doi: 10.1038 / s41418-023-01210-4. Epub 2023 Aug 21. PMID: 37605006;PMCID: PMC10482945.

[0042] L-Serine: Purchased from MedChemExpress LLC, purity ≥99%, catalog number: HY-N0650.

[0043] Serine hydrochloride: purchased from Shanghai Yuanye Biotechnology Co., Ltd., purity ≥99%, product number: S45281.

[0044] tert-butyl hydroperoxide (TBHP): purchased from Sigma-Aldrich, product number: A13926.

[0045] RBFOX2-siRNA: Purchased from General Biotechnology (Anhui) Co., Ltd., its designed and synthesized sequences are shown in SEQ ID NO: 1 and SEQ ID NO: 2: SEQ ID NO: 1:GCAAAUGGUUGGAAAUUAATT; SEQ ID NO: 2: UUAAUUUCCAACCAUUUGCTT.

[0046] Experimental animals: SPF-grade male SD rats, 8 weeks old, weighing 200-250g, purchased from Hubei Beinte Biotechnology Co., Ltd.

[0047] GSH test kit: purchased from Shanghai Beyotime Biotechnology Co., Ltd., product number: S0053.

[0048] ROS detection kit: purchased from Shanghai Beyotime Biotechnology Co., Ltd., product number: S0033S.

[0049] 1. Cell-level experiments Example 1 This embodiment provides a method for in vitro intervention of senescent nucleus pulposus cells, including the following steps: (1) Establishment of a cellular senescence model: Primary nucleus pulposus (NPCs) extraction: Collected nucleus pulposus tissue was minced, seeded, and expanded in DMEM medium containing F12 nutrient mixture (Cytiva, SH30023.01) and 10% fetal bovine serum (Hyclone, SH30406.05). Cells were cultured at 37°C and 5% CO2, and second-generation cells were used for subsequent experiments. NPCs were treated with 100 μM TBHP (Sigma-Aldrich, A13926) for 24 hours, followed by continued culture under normal conditions to induce and construct an in vitro cell senescence model.

[0050] (2) Serine treatment: exogenous L-serine solution (MedChemExpress, HY-N0650) was added to the cell culture medium for intervention, wherein the effective intervention concentration of serine was set to 1.0 mM.

[0051] (3) Effectiveness evaluation: Intracellular ROS level detection: After a certain period of culture, intracellular reactive oxygen species (ROS) were labeled using a reactive oxygen species (ROS) detection kit (Beyotime, S0033S) according to the instructions, and the fluorescence signal level of ROS was quantitatively detected by flow cytometry or fluorescence microscopy.

[0052] GSH content detection: Cells were collected, and the absorbance was detected using an ELISA reader according to the instructions of the GSH detection kit (Beyotime, S0053), and the relative change in intracellular glutathione (GSH) content was calculated.

[0053] SA-β-gal staining: After cell treatment, the cells were fixed, washed, and permeabilized. They were then stained using a senescence β-galactosidase staining kit (Beyotime, C0602), and the proportion of positive cells was observed and counted under a microscope.

[0054] Western blot analysis: Total cellular protein was extracted using RIPA lysis buffer (Beyotime, P0013B) supplemented with protease and phosphatase inhibitors. After separation by SDS-PAGE electrophoresis, the protein was transferred to a PVDF membrane. Primary antibodies against aging-related proteins P53 (Proteintech, 60283-2-Ig), P21 (Proteintech, 10355-1-AP), and the internal control GAPDH (Proteintech, 60004-1-Ig) were added, and the membrane was incubated overnight at 4°C. After washing, the membrane was incubated for 1 hour at room temperature with HRP-conjugated secondary antibody (Proteintech, SA00001-2 / 1). Finally, the membrane was detected using ECL imaging buffer (Affinity, KF001) in a chemiluminescence imaging system, and semi-quantitative analysis of protein expression was performed using ImageJ software.

[0055] Figure 2 The results showed that serine treatment significantly increased GSH levels (P<0.01) and significantly decreased ROS levels (P<0.01); the proportion of SA-β-gal positive cells was significantly reduced (P<0.01), and the expression levels of p53 and p21 proteins were downregulated. These results indicate that exogenous serine can effectively correct the redox imbalance in senescent nucleus pulposus cells and reverse the cellular senescence phenotype.

[0056] Example 2 Example 2 used the same cell source as Example 1, but the senescence model was established differently: an SSP pathway-damaged cell senescence model was established by knocking down RBFOX2 expression through transfection with RBFOX2-siRNA, instead of using TBHP induction. The serine treatment method was the same as in Example 1.

[0057] Example 3 Example 3 uses the same cell source, aging model establishment method and intervention steps as Example 1, the difference being that serine is replaced by serine hydrochloride.

[0058] 2. Animal-level experiments Example 4 This embodiment provides a method for treating lumbar intervertebral disc degeneration in rats by local injection of serine, including the following steps: (1) Animal model establishment: Eight-week-old SPF-grade male SD rats (weighing 200-250g) were selected. Anesthesia was performed via intraperitoneal injection of 3% sodium pentobarbital. After successful anesthesia, the rats were placed in a prone position with their tails fixed. Percutaneous punctures were performed at the Co7-8 and Co8-9 segments of the caudal vertebrae using a 20G needle. The needle was inserted at a 45° angle to the vertical to avoid caudal vessels. After passing through the center of the intervertebral disc, the needle was rotated 360° and held for 30 seconds before being slowly withdrawn to establish an in vivo IVDD model.

[0059] (2) Experimental grouping and drug intervention: Rats that successfully established the model were randomly divided into a model control group and a serine treatment group. A 31G needle was used to inject a small amount of serine solution into the center of the degenerated intervertebral disc. The serine treatment group received a local injection of 10 μL of 100 mM L-serine solution periodically (e.g., on days 1, 7, 14, and 21) after model establishment; the model control group received an equal volume of physiological saline. The needle was kept in the intervertebral disc for 10 seconds during injection to prevent leakage of the drug solution.

[0060] (3) Evaluation of therapeutic effect: Imaging examinations: Four weeks after intervention, rats underwent MRI, X-ray, and Micro-CT scans. MRI parameters were set as follows: repetition time (TR) 2000 ms, echo time (TE) 36 ms, matrix 256×256. Pfirrmann degeneration grade was assessed using T2-weighted signal intensity and nucleus pulposus water content. Micro-CT parameters were set as follows: voltage 70 kV, current 200 μA, resolution 18 μm, used to detect disc height index (DHI) and endplate bone mineral density changes.

[0061] Histological assessment: After sampling, the intervertebral disc tissue was fixed overnight in 4% paraformaldehyde, decalcified, dehydrated, and embedded in paraffin before being sectioned. H&E staining, Safranin O-Fixed Green (SO-FG) staining, and Masson staining were performed to observe the morphology of nucleus pulposus cells, the distribution of extracellular matrix (such as collagen and proteoglycans), and the degree of tissue fibrosis. The Masuda histological scoring system was used to quantify the degree of degeneration.

[0062] Figure 3 and Figure 4The results showed that the MRI signal of the intervertebral discs of rats in the serine treatment group was significantly preserved, and the histological degeneration score was significantly lower than that in the saline control group, proving that it has excellent repair-promoting effects in vivo.

[0063] Example 5 This embodiment 5 provides a method for treating lumbar intervertebral disc degeneration in rats by local injection of serine-loaded thermosensitive hydrogel, including the following steps: (1) Preparation of serine-loaded injectable hydrogel: Under sterile conditions, a pharmaceutically acceptable thermosensitive polymer matrix, chitosan-sodium glycerophosphate system, was slowly dissolved in sterile PBS and continuously stirred at 4°C until completely dissolved to prepare a hydrogel precursor solution. Subsequently, L-serine was added to the precursor solution in a predetermined ratio and mixed thoroughly to achieve a final concentration of 100 mM. The solution was then stored at 4°C for later use. The system is an easily injectable liquid at refrigeration and room temperature, and can rapidly undergo a phase transition to form a solid gel at a body temperature of 37°C.

[0064] (2) Animal model establishment: Eight-week-old SPF-grade male SD rats (weighing 200-250g) were selected. After intraperitoneal anesthesia with 3% sodium pentobarbital, the rats were placed in a prone position and fixed. At the Co7-8 and Co8-9 segments of the caudal vertebrae, a 20G puncture needle was inserted into the center of the intervertebral disc at a 45° angle, avoiding the caudal blood vessels. The needle was rotated 360° and held for 30 seconds before being slowly withdrawn to establish an in vivo IVDD model.

[0065] (3) Experimental grouping and drug intervention: Rats that successfully developed the model were randomly divided into a model control group and a hydrogel treatment group, with 6 rats in each group. Using a 31G microsyringe, on the first day after modeling, 10 μL of serine-loaded thermosensitive hydrogel, kept in a liquid state, was slowly injected into the center of the degenerated intervertebral disc in the hydrogel treatment group. After injection, the needle remained in place for 2 minutes to allow the hydrogel to cross-link in place under the action of body temperature (37°C) and seal the needle path to prevent drug leakage; the model control group was injected with an equal amount of blank hydrogel without drug. Thanks to the sustained-release properties of the hydrogel, only a single dose was required for the entire treatment course.

[0066] (4) Evaluation of efficacy and sustained release: After 4 weeks of intervention, rats underwent small animal MRI and Micro-CT scans. The Pfirrmann degeneration grade was assessed using T2-weighted signal intensity and nucleus pulposus water content, and the intervertebral disc height index (DHI) was calculated. After sampling, the intervertebral disc tissue was fixed, decalcified, and embedded in paraffin. H&E staining, Safranin O-Fix Green (SO-FG) staining, and Masson staining were performed to assess extracellular matrix remodeling and fibrosis reversal, confirming that the serine-loaded hydrogel could achieve long-term targeted release in vivo, continuously correct the redox imbalance of nucleus pulposus cells, and significantly reverse their aging process.

[0067] In the description of this specification, the references to terms such as "one embodiment / mode," "some embodiments / modes," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment / mode or example is included in at least one embodiment / mode or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment / mode or example. Moreover, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments / modes or examples. Furthermore, without contradiction, those skilled in the art can combine and integrate the different embodiments / modes or examples described in this specification, as well as the features of different embodiments / modes or examples.

[0068] It should be noted that in this application, relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element. In this application, "a plurality of" means at least two, such as two, three, etc., unless otherwise expressly specified.

[0069] The above description is merely a specific embodiment of this application, enabling those skilled in the art to understand or implement this application. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of this application. Therefore, this application is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features claimed herein.

Claims

1. The use of serine or a pharmaceutically acceptable salt thereof in the preparation of drugs for the prevention or treatment of intervertebral disc degeneration.

2. Use according to claim 1, wherein The serine includes L-serine.

3. The application as described in claim 1, characterized in that, The drug includes at least one of a locally injectable formulation and an oral formulation.

4. The application as described in claim 3, characterized in that, The local injection formulation is an intradiscal injection formulation selected from at least one of aqueous solution, suspension, in-situ hydrogel, and sustained-release microspheres.

5. The application as described in claim 3, characterized in that, The locally injectable formulation comprises a locally sustained-release delivery system made of biomaterials.

6. The application as described in claim 1, characterized in that, The intervertebral disc degeneration is accompanied by nucleus pulposus cell senescence and / or intracellular redox imbalance.

7. A pharmaceutical composition for the prevention or treatment of intervertebral disc degeneration, characterized in that, The pharmaceutical composition uses serine or a pharmaceutically acceptable salt thereof as the active ingredient and contains pharmaceutically acceptable excipients and / or a biological sustained-release carrier.

8. The pharmaceutical composition according to claim 7, characterized in that, The pharmaceutical composition is formulated for administration via local intradiscal injection.

9. A kit for the prevention or treatment of intervertebral disc degeneration, characterized in that, Includes the pharmaceutical composition and injection device as described in claim 7 or 8.

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