Application of mouse nerve growth factor in preparation of medicine for treating animal inflammation and medicine

Abstract

The invention belongs to the technical field of biological medicine, and particularly relates to application of a mouse nerve growth factor in preparation of a medicine for treating animal inflammation and the medicine. Wherein the application refers to the application of the mouse nerve growth factor in preparation of drugs for treating animal inflammation including chronic gingival stomatitis, and the active ingredient of the drugs is the mouse nerve growth factor; the medicine has the function of treating animal inflammations including chronic gingival stomatitis; the medicine for treating chronic gingival stomatitis of animals is prepared by using simple and easily available mouse nerve growth factors as active substances, the curative effect is remarkable, and the living quality of sick cats is finally improved.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedicine, and specifically relates to the application of mouse nerve growth factor in preparing a drug for treating animal inflammation and a drug. Background Art

[0002] Murine nerve growth factor (mNGF) is a potent neurotrophic factor in the neurotrophic factor family and has received widespread attention from the scientific community for its diverse biological activities and therapeutic potential. This protein plays a key role in the development, maintenance and repair of the nervous system, especially in promoting neuronal survival, differentiation and neural connection formation. mNGF exerts its effects by binding with high affinity to its receptor tropomyosin receptor kinase A (TrkA), triggering a series of intracellular signaling pathways, regulating gene expression, and ultimately affecting neuronal function and plasticity. For example, Chinese invention patent application No. CN202311159241.6 discloses a pharmaceutical composition for preventing and treating sequelae of facial nerve paralysis and its application.

[0003] Mouse nerve growth factor (mNGF) is a freeze-dried product of nerve growth factor isolated and purified from mouse submandibular gland. Its traditional preparation process is: homogenize mouse submandibular gland tissue to obtain homogenate supernatant; then centrifuge the homogenate supernatant, remove the precipitate, and perform ion exchange chromatography to collect the flow-through; acidify the flow-through and centrifuge to obtain acid hydrolysis supernatant; perform ion exchange chromatography on the acid hydrolysis supernatant to collect the target protein peak to obtain the nerve growth factor stock solution; then add excipient mannitol and stabilizer human serum albumin, sterilize and filter, divide and freeze-dry to obtain the product. CN200810071315.X invention patent application discloses a preparation method of mouse nerve growth factor (NGF) and a preparation method of mouse nerve growth factor for injection. It adds 100KD and 5KD ultrafiltration membrane filtration and pasteurization technology to the traditional process, which can effectively filter large molecular viruses. At the same time, it further inactivates potential viruses such as pseudorabies virus (PRV), Sindbis virus, encephalomyocarditis (EMC) virus through pasteurization. It does not introduce any foreign organic solvents, detergents and other pollutants, while maintaining the high purity, high specific activity and high safety of mouse nerve growth factor.

[0004] It can be seen that the preparation method of mouse nerve growth factor (mNGF) obtained by separation and purification from mouse submandibular gland is becoming mature, can be mass-produced, and has high activity, safety and stability. The mouse nerve growth factor drug on the market is an intramuscular injection drug. It has been reported in the prior art that the drug form and function of the mouse nerve growth factor drug have been studied.

[0005] In order to develop topical drugs, Chinese patent No. CN200310120873.8 provides a topical nerve growth factor agent that overcomes the disadvantages of antibiotic drugs, such as cream, emulsion and hyaluronic acid gel and its preparation method. Its NGF topical agent has an effective rate of 87.5% for scalp psoriasis, gynecological pruritus, lichen sclerosus malnutrition, and hypertrophic malnutrition; 100% effective rate for acute and chronic eczema; 100% effective rate for chapped skin.

[0006] Chinese patent No. CN201711452347.X discloses a hydrogel containing nerve growth factor and its preparation method, which is used for the treatment of refractory ulcers such as pressure ulcers. Pressure ulcers (PU), also known as bedsores, are local ischemic damage to the skin and the tissues below due to the obstruction of blood and lymph flow caused by external pressure. It is one of the most common complications in clinical practice. The nerve growth factor in the nerve growth factor solution is a drug active ingredient that promotes the healing of wounds and ulcers and accelerates the formation of new blood vessels.

[0007] At the same time, in terms of regulating the growth of bone and / or gingival tissue, the invention patent application No. CN201880035580.4 provides a biocompatible composition comprising a biocompatible polymer matrix and an adjusted cell culture medium, wherein the adjusted cell culture medium comprises: i) a cell culture medium and ii) one or more agents synthesized and secreted by one or more cells cultured in the cell culture medium, and its therapeutic use, especially in regulating the growth of bone and / or gingival tissue. In the embodiment provided by the invention application technology, the composition is used to maintain or increase bone mass, maintain or increase bone density, maintain or increase gingival tissue, or any combination thereof. In another embodiment, an effective amount of a) promoting gingival and / or bone growth and / or b) a therapeutic agent that inhibits gingival erosion and / or bone resorption is administered to the subject.

[0008] In summary, mouse nerve growth factor (mNGF) has been used in existing technologies to reduce nerve damage and promote neuron regeneration; promote wound and ulcer healing, accelerate neovascularization; maintain or increase bone mass, maintain or increase bone density, and maintain or increase gingival tissue.

[0009] Chronic feline gingivostomatitis (FCGS) is a serious oral inflammatory disease that is highly disabling and characterized by persistent pain and considerable oral discomfort in affected cats. This condition manifests itself in a range of clinical manifestations that severely compromise the quality of life and life expectancy of affected cats. Symptoms include, but are not limited to, moderate to severe pain symptoms, often accompanied by excessive salivation (typically), halitosis and other noxious breath odors, progressive weight loss due to difficulty eating, extreme irritability caused by pain, and a significant decrease in physical activity and overall health. The complexity of the pathogenesis of FCGS itself and other multifaceted causes in the husbandry process constitute a huge obstacle to the implementation and realization of clear and effective clinical management strategies. Although it has been previously reported that tooth extraction surgery can significantly improve the clinical manifestations of FCGS in many cases, a considerable number of affected cats still require long-term analgesic and immunosuppressive drug interventions to control inflammation. Given the heavy burden that FCGS places on affected cats and their owners and caregivers, research exploring new therapeutic agents and treatment modalities is urgently needed. These efforts must be aimed at reducing inflammation and ultimately improving the quality of life of affected cats. The design and validation of these treatment strategies has the potential to transform the clinical management of FCGS and bring hope to affected cats and their owners.

[0010] FCGS makes it impossible for cats to eat or drink, and the owner must help (force) feed them or use parenteral nutrition to maintain their lives. FCGS makes it impossible for cats to open their mouths, so they cannot complete social activities such as grooming and vocalizing. It meets the condition of physical and mental damage caused by the disease, resulting in loss of living and social abilities. In addition to FCGS, other inflammatory diseases in cats, dogs, and other animals include otitis externa, otitis media, and otitis interna, which seriously affect the normal daily activities of animals.

[0011] Therefore, there is an urgent need to develop a drug that can effectively control inflammation in animals. Summary of the invention

[0012] To solve the above problems, the purpose of the present invention is to provide an application of mouse nerve growth factor in the preparation of drugs for treating animal inflammation and a drug, that is, using the simple and easily available mouse nerve growth factor as an active substance to prepare drugs for treating inflammatory diseases such as chronic gingivostomatitis in animals, and ultimately improving the quality of life of sick animals.

[0013] To achieve the above-mentioned purpose, the technical solution adopted by the present invention is: application of mouse nerve growth factor, wherein the application is application of mouse nerve growth factor in the preparation of a drug for treating animal inflammation.

[0014] Optimized, the application is the use of mouse nerve growth factor in the preparation of a drug for treating chronic gingivostomatitis in animals.

[0015] Optimized, the application is the use of mouse nerve growth factor in the preparation of a drug for treating chronic gingivostomatitis in domestic cats.

[0016] Optimally, the mouse nerve growth factor is separated and purified from the mouse submandibular gland; the drug also includes other pharmaceutically acceptable carriers and excipients.

[0017] Optimally, the drug also includes sodium dihydrogen phosphate, disodium hydrogen phosphate, human serum albumin, and mannitol; and the drug is administered by injection.

[0018] Optimally, the single administration dose of the drug is 0.3-27 micrograms / kg / day.

[0019] Optimally, the single administration dose of the drug is 0.9-2.7 micrograms / kg / day.

[0020] The present invention provides a medicine, the active ingredient of which is mouse nerve growth factor; the function of the medicine is to treat animal inflammation.

[0021] The function of the drug is to treat chronic gingivostomatitis in domestic cats; the drug also includes sodium dihydrogen phosphate, disodium hydrogen phosphate, human serum albumin, and mannitol; the drug is administered by injection; and the single dose of the drug is 0.3-27 micrograms / kg / day.

[0022] Optimally, the single administration dose of the drug is 0.9-2.7 micrograms / kg / day.

[0023] The present invention adopts mouse nerve growth factor as an active substance to prepare a drug for treating inflammatory diseases such as chronic gingivostomatitis in animals. The mechanism is as follows: from the perspective of molecular biology, mNGF reduces inflammation in cat oral mucosa and the like and plays a role in molecular pathways and cell targets. Because a variety of cytokines involved in inflammation, such as IL-1β, TNF-α, and IL-6, are promoting factors of a variety of mNGFs. And mNGF regulates inflammatory responses through a variety of pathways. For example, mNGF can inhibit cell apoptosis by activating the TrkA pathway and then regulating the expression of Bcl-2, Bcl-xl, and Bfl-1. TrkA is stably expressed in blood monocytes, thymocytes, human B lymphocytes and T lymphocytes, monocytes, mast cells, basophils, eosinophils, and neutrophils. Under inflammatory conditions, it will additionally induce immune cells to synthesize neuropeptides with immunoregulatory functions. mNGF can also promote the secretion of p75NTR (p75 neurotrophic factor receptor), which is widely expressed in lymphoid organs, promotes the maturation and differentiation of T cells and B cells, and then participates in immune and inflammatory regulation. In addition, it reduces the production of inflammatory factors by reducing interferon-γ, increasing IL-10, weakening TLR signal transduction, and downregulating NF-κB.

[0024] The beneficial effects of the present invention are:

[0025] 1. Animal inflammatory diseases such as feline chronic gingivostomatitis (FCGS), also known as feline stomatitis, are a common and disabling inflammatory disease that affects the oral health of domestic cats and is a major challenge for the veterinary community. The present invention aims to provide the use of mouse nerve growth factor (mNGF) as an active ingredient in the preparation of drugs for the treatment of inflammatory diseases such as chronic gingivostomatitis in animals. The present invention conducted a comprehensive clinical evaluation, including weight loss monitoring, symptom assessment, quantification of inflammatory responses, hematological and biochemical analysis, and histological examination of inflammatory tissue changes. The results showed that the clinical parameters of cats treated with mNGF were significantly improved compared with the FCGS group. These results collectively indicate that mNGF is a very promising candidate therapeutic drug for the treatment of FCGS in domestic cats, providing a safe and effective alternative to traditional treatment options; that is, the present invention has developed a new application of mouse nerve growth factor as an active substance to reduce inflammation and ultimately improve the quality of life of sick animals / cats.

[0026] 2. The preparation method of mouse nerve growth factor (mNGF) separated and purified from mouse submandibular gland is mature, can be mass-produced, and has high activity, safety and stability. Mouse nerve growth factor drugs are easy to obtain for intramuscular injection.

[0027] 3. Furthermore, the present invention studies and obtains the single dosage and treatment course of mouse nerve growth factor for treating FCGS in domestic cats.

[0028] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] The present invention is further described below in conjunction with the accompanying drawings and embodiments;

[0030] Figure 1 This is a diagram showing the weight loss of animals during the experiment in a specific embodiment of the present invention;

[0031] Figure 2 This is a comparison of histological staining of inflammatory reactions in a specific embodiment of the present invention - a treatment group diagram;

[0032] Figure 3 This is a comparison of histological staining of inflammatory response in a specific embodiment of the present invention and a healthy control group;

[0033] Figure 4 This is a group of pictures of FCGS, a comparison of histological staining of inflammatory reactions in a specific embodiment of the present invention;

[0034] Figure 1 Indicates the weight loss of animals. The three bars in the figure represent the treatment group, FCGS (stomatitis) group and healthy (control) group from top to bottom. The weight loss of the treatment group was within 0.5kg, the weight loss of the FCGS (stomatitis) group was within 1.5kg, and the weight gain of the healthy control group was within 0.5kg.

[0035] Figure 4 It means that after the infiltration of inflammatory factors, cells are damaged, die, and disintegrate, which causes macroscopic destruction of tissue continuity, ulcers, erosions, bleeding, etc. Figure 4 The circled area in the middle is the area of ​​tissue destruction and ablation. DETAILED DESCRIPTION

[0036] This section will describe in detail the specific embodiments of the present invention. The preferred embodiments of the present invention are shown in the accompanying drawings. The purpose of the accompanying drawings is to supplement the description of the text part of the specification with graphics, so that people can intuitively and vividly understand each technical feature and the overall technical solution of the present invention, but it cannot be understood as a limitation on the scope of protection of the present invention.

[0037] The technical solution adopted in this embodiment is: application of mouse nerve growth factor, and the application is application of mouse nerve growth factor in the preparation of drugs for treating animal inflammation.

[0038] Among them, the application is the application of mouse nerve growth factor in the preparation of drugs for treating chronic gingivostomatitis in animals.

[0039] Among them, the application is the application of mouse nerve growth factor in the preparation of a drug for treating chronic gingivostomatitis in domestic cats.

[0040] The mouse nerve growth factor is separated and purified from the mouse submandibular gland; the drug also includes other pharmaceutically acceptable carriers and excipients.

[0041] The medicine also includes sodium dihydrogen phosphate, disodium hydrogen phosphate, human serum albumin and mannitol; the medicine is administered by injection.

[0042] Wherein, the single dosage of the drug is 0.3-27 micrograms / kg / day.

[0043] Wherein, the single dosage of the drug is 0.9-2.7 micrograms / kg / day.

[0044] This embodiment provides a drug, wherein the active ingredient of the drug is mouse nerve growth factor; the function of the drug is to treat animal inflammation.

[0045] The function of the drug is to treat chronic gingivostomatitis of domestic cats; the drug also includes sodium dihydrogen phosphate, disodium hydrogen phosphate, human serum albumin, and mannitol; the drug is administered by injection; and the single dose of the drug is 0.3-27 micrograms / kg / day.

[0046] Wherein, the single dosage of the drug is 0.9-2.7 micrograms / kg / day.

[0047] In this embodiment, the experimental animals were grouped and treated with mNGF as follows:

[0048] Domestic cats were divided into 3 groups: healthy group, FCGS group and treatment group. Healthy cats were negative for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV), without any systemic diseases (diabetes, inflammatory bowel disease), and without taking antibiotics or immunomodulatory drugs within one month before sampling. These cats were considered clinically oral healthy without any signs of oral diseases (n=10). The FCGS group indicated that the cats were diagnosed with FCGS. The treatment group was given mNGF subcutaneously at the back of the neck once a day for 23 consecutive days. A gradual increase in dosage and maintenance treatment after reaching a certain dose was adopted. From the first to the ninth day of medication, the starting dose was 0.3 micrograms / kg body weight / day (μg / kg / day), and the dose was increased by 0.3 micrograms / kg body weight / day (μg / kg / day) every day. After increasing to 2.7 micrograms / kg body weight / day (μg / kg / day) on the ninth day, the dose was maintained for 14 days, with a total treatment cycle of 23 days. The general information of all clinical validation samples, including age, gender, weight, and medication dosage, are summarized in Table 1, Table 2-1, and Table 2-2.

[0049] Table 1

[0050]

[0051] Table 2-1

[0052]

[0053] Table 2-2

[0054]

[0055] In this embodiment, the administration of mNGF / administration of mNGF drug treatment / mNGF treatment described above and in this patent refers to the use of the commercially available Sutepsen mouse nerve growth factor drug for injection produced by Shutaishen (Beijing) Biopharmaceutical Co., Ltd., whose active ingredient is the nerve growth factor (mNGF) extracted and purified from the submandibular gland of mice, which is a biologically active protein with a molecular weight of 26.5KD, and the names of the excipients are: sodium dihydrogen phosphate, disodium hydrogen phosphate, human serum albumin, mannitol. In this embodiment, the "drug (dose) amount" of the administration of mNGF / administration of mNGF drug treatment / mNGF treatment and the "single dose of the drug" in this patent all refer to the amount of the commercially available Sutepsen mouse nerve growth factor drug for injection produced by Shutaishen (Beijing) Biopharmaceutical Co., Ltd. Because each bottle of Sutepsen is 30 micrograms (powder) / bottle, the amount of mouse nerve growth factor (mNGF) contained in each bottle of standard weight mixture is 15000U, that is, 1 microgram = 500U. Therefore, the amount of the active ingredient mouse nerve growth factor in the dosage is, from the first day to the ninth day, with a starting dose of 150U / kg body weight / day, increased by 150U / kg body weight / day every day, and after increasing to 1350U / kg body weight / day on the ninth day, maintained at this dose for 14 days of treatment, with a total treatment cycle of 23 days.

[0056] The analysis items of the above experiment in this embodiment are as follows:

[0057] Blood analysis: 0.25 ml of blood was drawn and transferred into a glass container pre-filled with 0.5 μl of EDTA, which was then sealed and marked for identification. Blood samples were stored in tubes with 10% EDTA for hematological evaluation. The Sysmex XN1000 hematology analyzer was used to determine the counts of red blood cells, white blood cells, and platelets.

[0058] Clinical evaluation: A clinical assessment of the trauma area was performed by two independent assessors. The objectives were to determine the presence of lesions, quantify the size of the lesions with a probe, and classify the occurrence and intensity of FCGS according to the following modified classification system:

[0059] 1. Normal

[0060] 2. Erythema

[0061] 3. Epithelial shedding

[0062] 4.25% of surface ulcers

[0063] 5. Surface ulcers more than 25% to 50%

[0064] 6. Surface ulcers above 50% to 75%

[0065] 7. Surface ulcers more than 75%

[0066] This adaptive classification, derived from the works of Ottaviani et al., Patel, Biswas, Shoja, Ramalingayya, and Nandakumar, ensures a standardized approach to the assessment of oral conditions following trauma.

[0067] Histological evaluation: After clinical examination, ulcer tissue was carefully excised from each animal by surgery. The excised tissue was immersed in 10% formaldehyde solution for 24 hours, and then the sample was embedded in paraffin for histological processing, and three consecutive sections were produced for each sample, each with a thickness of 3 microns. These sections were carefully prepared and then stained with hematoxylin and eosin (HE) staining technique.

[0068] Microscopic evaluation was performed using an Olympus binocular microscope, and the area with the most obvious inflammatory response was scored according to the following criteria:

[0069] 1. None: No inflammation

[0070] 2. Mild: sparse monocytes

[0071] 3. Moderate: mononuclear infiltration and / or sparse neutrophils and eosinophils

[0072] 4. Severe: Polymorphonuclear infiltration of neutrophils and eosinophils

[0073] Statistical analysis: SPSS 17.0 software was used to tabulate and evaluate the data. Variance analysis and Tukey test were performed.

[0074] The analysis results are as follows:

[0075] The results of the weight change analysis of cats were as follows: In this study, the researchers selected 10 healthy cats and 20 cats diagnosed with FCGS as research subjects, so the number of cats in the healthy group, FCGS group, and treatment group was 10, respectively. Table 1 comprehensively records the baseline weight of these diseased cats. During the experimental period, healthy cats showed significant weight gain after two weeks, which was attributed to adequate nutritional intake. In contrast, the FCGS cohort showed significant weight loss due to feeding difficulties and decreased appetite caused by the disease.

[0076] After treatment with mouse nerve growth factor (mNGF), all cats affected by FCGS showed a reduction in weight loss compared with the untreated FCGS group. Figure 1 Although the magnitude of weight changes in the treatment groups was not completely consistent with that observed in the healthy control group, these findings preliminarily suggest that mNGF has the potential to mitigate weight loss associated with FCGS. Figure 1 As shown in the results, the weight of the healthy group increased, and the weight of the FCGS group and the treatment group decreased to varying degrees. The stomatitis group showed a significant weight loss compared with the healthy control group (P less than 0.01), and the treatment group also showed a weight loss compared with the healthy control group (p less than 0.01), but the weight loss of the treatment group was significantly smaller than that of the FCGS group.

[0077] The results of the clinical evaluation and analysis were as follows: In the investigation and study of the present invention, a strict and standardized protocol was used to evaluate the post-traumatic oral condition of cats. As shown in Table 3, the control group consisting only of healthy cat subjects was always clustered in the lowest grade (grade 1), showing a pristine oral mucosa without any identifiable surface damage. In sharp contrast, the FCGS cohort fell mainly in grades 5 to 7, with a specific distribution of 3, 3, and 4 cats, respectively. This stratification emphasizes the severity of oral ulcers, with 3 cats having ulcer areas exceeding 25% to 50% of the oral surface, 3 cats having ulcer areas exceeding 50% to 75%, and 4 cats having ulcer areas exceeding 75%. This degree of ulceration is a major challenge in treatment, which seriously disrupts the normal feeding pattern of cats and has subsequent effects on their growth and development.

[0078] After intervention with murine nerve growth factor (mNGF), varying degrees of improvement in oral health were observed in the FCGS group. Of note, although 1–2 cats still exhibited grade 4 and 5 mucosal destruction, we hypothesize that this persistence may be attributed to individual differences between cats or differences in individual dietary preferences.

[0079] Table 3

[0080]

[0081] Note:

[0082] 1. Normal

[0083] 2. Erythema

[0084] 3. Epithelial shedding

[0085] 4.25% of surface ulcers

[0086] 5. Surface ulcers more than 25% to 50%

[0087] 6. Surface ulcers above 50% to 75%

[0088] 7. Surface ulcers more than 75%

[0089] The results of blood analysis are as follows: Table 4 is a comprehensive analysis of red blood cell, white blood cell and platelet counts at the end of a total of 23 days of treatment, stratified by experimental group. The results showed that the red blood cell (healthy group: 9.21±0.75; FCGS group: 8.61±0.30; treatment group: 8.85±0.12) and white blood cell (healthy group: 6.45±1.23; FCGS group: 10.84±0.59; treatment group: 6.15±1.18) and platelet counts (healthy group: 1560.25±105.8; FCGS group: 1630.11±99.0; treatment group: 1414.11±106.8) in the healthy control group, FCGS group and treatment group were significantly increased compared with the healthy control group, which is consistent with the inflammatory disease model, where white blood cells undergo rapid activation to counteract inflammatory stimuli. Notably, the rapid decline and eventual normalization of leukocyte counts after mNGF administration emphasizes the excellent anti-inflammatory potential of mNGF and highlights its therapeutic significance.

[0090] Table 4

[0091]

[0092] The results of inflammatory response and histological analysis were as follows: After completing the 23-day treatment regimen, the inflammatory response scores of the three different groups of cat subjects were carefully evaluated, as shown in Table 5. The healthy control group had no inflammatory response, and the FCGS group showed a significant inflammatory response. After administering mNGF treatment and monitoring the progression of inflammation severity, we observed a significant decrease in the inflammatory score in the mNGF-treated group, showing a transition from severe to mild or moderate. Specifically, after treatment, 4 cats showed mild inflammation and 6 cats showed moderate inflammation.

[0093] Table 5

[0094]

[0095]

[0096] Note:

[0097] 1. None: No inflammation

[0098] 2. Mild: sparse monocytes

[0099] 3. Moderate: mononuclear infiltration and / or sparse neutrophils and eosinophils

[0100] 4. Severe: Polymorphonuclear infiltration of neutrophils and eosinophils

[0101] In order to further understand the histopathological changes, the present invention adopts HE staining. Figure 2-4 The results showed that in the FCGS group before treatment, there was a significant inflammatory infiltrate, mainly composed of polymorphonuclear cells, indicating severe inflammation with edema and ulceration. In contrast, after mNGF intervention, microscopic examination showed that the inflammatory infiltrate was mainly composed of mononuclear cells, mixed with neutrophils and a small number of eosinophils, indicating that the inflammatory process was alleviated to moderate inflammation with epithelial ulceration.

[0102] The overall therapeutic effect of mNGF treatment was highlighted by the results of HE staining analysis, which showed a substantial reduction in overall inflammation. Although residual inflammation was still present in individual treated cats, the overall inflammatory status was significantly improved, highlighting the potential of mNGF as a therapeutic agent to alleviate inflammatory conditions. Figure 2-4 The following are histological staining comparisons of inflammatory reactions. In the healthy group, the microphotographs showed sparse mononuclear cells, indicating no inflammation or mild inflammation (HE, 100×); in the FCGS group, the microphotographs showed polymorphonuclear cell inflammatory infiltration, indicating severe inflammation, edema and ulceration (HE, 100×); in the treatment group, the microphotographs showed mononuclear cell inflammatory infiltration, accompanied by sparse neutrophils and eosinophils, indicating moderate inflammation with epithelial ulceration (HE, 100×).

[0103] The above studies found that mNGF has the potential to treat FCGS in animals / domestic cats, including providing increasing evidence for the multifaceted role of neurotrophic factors in regulating oral inflammatory processes. First, the present invention observed improvements in clinical symptoms in cats treated with mNGF, emphasizing that the drug has a significant therapeutic effect in treating FCGS. Clinical evaluations and owner reports demonstrated weight loss, inflammation, and tissue ulcers, indicating that mNGF has a direct or indirect effect on the underlying pathological mechanisms of FCGS and reduces inflammation.

[0104] In summary, the present invention has developed the potential of mNGF as an active pharmaceutical ingredient for the treatment of FCGS in domestic cats. The improvements in clinical symptoms and blood biochemistry observed in the present invention suggest that mNGF provides a new and effective treatment option for this disabling disease.

[0105] The embodiments of the present invention are described in detail above with reference to the accompanying drawings. However, the present invention is not limited to the above embodiments. Various changes can be made within the knowledge scope of ordinary technicians in the technical field without departing from the purpose of the present invention.

Claims

1. The application of mouse nerve growth factor is characterized by: The application is the application of mouse nerve growth factor in preparing medicine for treating animal inflammation.

2. The use of mouse nerve growth factor according to claim 1, characterized in that: The application is the application of mouse nerve growth factor in preparing medicine for treating chronic gingivostomatitis in animals.

3. The use of mouse nerve growth factor according to claim 2, characterized in that: The application is the application of mouse nerve growth factor in preparing medicine for treating chronic gingivostomatitis of domestic cats.

4. The use of the mouse nerve growth factor according to any one of claims 1 to 3, characterized in that: The mouse nerve growth factor is separated and purified from the mouse submandibular gland; the medicine also includes other pharmaceutically acceptable carriers and auxiliary materials.

5. The use of mouse nerve growth factor according to claim 4, characterized in that: The medicine also includes sodium dihydrogen phosphate, disodium hydrogen phosphate, human serum albumin and mannitol; the medicine is administered by injection.

6. The use of mouse nerve growth factor according to claim 5, characterized in that: The single administration dose of the drug is 0.3-27 micrograms / kg / day.

7. The use of mouse nerve growth factor according to claim 5, characterized in that: The single administration dose of the drug is 0.9-2.7 μg / kg / day.

8. A medicine, characterized in that: The active ingredient of the medicine is mouse nerve growth factor; the function of the medicine is to treat animal inflammation.

9. A medicine according to claim 8, characterized in that: The function of the medicine is to treat chronic gingivostomatitis inflammation of domestic cats; the medicine also includes sodium dihydrogen phosphate, disodium hydrogen phosphate, human serum albumin, and mannitol; the administration method of the medicine is injection; the single administration dose of the medicine is 0.3-27 micrograms / kg / day.

10. A medicine according to claim 9, characterized in that: The single administration dose of the drug is 0.9-2.7 μg / kg / day.

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