Application of carbasalate calcium in preparation of medicine for treating hydrocephalus

Abstract

The invention discloses application of carbaspillin calcium in preparation of a medicine for treating hydrocephalus, belongs to the technical field of medicines for treating hydrocephalus, and particularly relates to application of carbaspillin calcium in preparation of a medicine for treating hydrocephalus, and the medicine takes carbaspillin calcium as a unique or main effective component. The effect of carbaspillin calcium in treating hydrocephalus is found for the first time, the fourth ventricle area of the hydrocephalus model zebrafish can be remarkably reduced, and the swimming distance, swimming time, swimming speed and rotational motion frequency of the hydrocephalus model zebrafish can be remarkably increased; experimental data provided by the invention show that the carbaspillin calcium has a huge application prospect in treatment of hydrocephalus, and an effective candidate drug is provided for relieving the treatment pain of a patient with hydrocephalus and reducing the treatment risk and cost; and the action range of the carbaspirin calcium is widened.

Description

Technical Field

[0001] The invention relates to the technical field of hydrocephalus therapeutic drugs, in particular to application of carbaspirin calcium in preparing hydrocephalus therapeutic drugs. Background Art

[0002] Hydrocephalus is a condition in which cerebrospinal fluid accumulates abnormally in the skull, usually due to cerebrospinal fluid circulation disorders, absorption disorders, or excessive secretion. According to the causes of formation, hydrocephalus is mainly divided into two categories: obstructive hydrocephalus and communicating hydrocephalus. Obstructive hydrocephalus is caused by obstruction of the circulation path of cerebrospinal fluid, which can be caused by congenital defects (such as Chiari malformation), tumors, infections (such as meningitis), bleeding (such as blood clots after subarachnoid hemorrhage), or other inflammatory diseases. The obstruction may occur somewhere in the ventricles, such as the pores between the ventricles or the passage from the ventricles to the subarachnoid space. Communicating hydrocephalus is a condition in which the circulation path of cerebrospinal fluid is not physically blocked, but the accumulation of cerebrospinal fluid is caused by absorption disorders. It may be caused by meningeal inflammation, head trauma, treatment of certain types of brain tumors (such as radiotherapy), or decreased cerebrospinal fluid absorption capacity during natural aging. In addition, hydrocephalus may also be related to genetic factors, congenital defects, or certain disease states.

[0003] Hydrocephalus can occur at any age, from newborns (infantile hydrocephalus) to the elderly. Existing statistics show that the incidence of hydrocephalus is about 1‰ in children and about 2‰ in the elderly. Hydrocephalus may cause increased intracranial pressure and trigger a series of neurological symptoms and signs. The specific symptoms vary depending on the patient's age, cause and severity of the disease. Common symptoms include headache, vomiting, optic disc edema (causing vision problems), difficulty walking, cognitive impairment, and abnormal increase in head circumference in children.

[0004] Traditional treatments for hydrocephalus mainly include the following: 1) Shunt surgery, which is the most common treatment method. A catheter (shunt) is placed inside or outside the ventricle of the brain through surgery to drain excess cerebrospinal fluid to other parts of the body, usually the abdominal cavity (called ventriculoperitoneal shunt), and sometimes to the atrium or chest cavity. The shunt is equipped with a valve that can adjust the flow rate of cerebrospinal fluid to maintain normal intracranial pressure. 2) Endoscopic surgery. With the development of neuroendoscopic technology, endoscopic third ventriculostomy (ETV) or endoscopic choroid plexus coagulation can be used to treat certain types of obstructive hydrocephalus, especially hydrocephalus caused by stenosis or obstruction. ETV surgery is to create a small hole at the bottom of the third ventricle through an endoscope to allow cerebrospinal fluid to flow directly into the subarachnoid space, thereby restoring the normal circulation of cerebrospinal fluid. 3) Drug treatment. Although drugs cannot cure hydrocephalus, in some cases, such as mild or temporary hydrocephalus, or as an adjunct to surgery, drugs may be used to reduce the production of cerebrospinal fluid or help control patient symptoms. Currently, commonly used drugs are diuretics.

[0005] Shunt surgery and endoscopic surgery have certain risks and complications, including infection, catheter blockage, and excessive drainage. Currently, there is no drug approved by the National Medical Products Administration for the treatment of human hydrocephalus.

[0006] The main ingredients of carbaspirin calcium are aspirin and calcium salt. It combines the antipyretic, analgesic and anti-inflammatory effects of aspirin with the calcium supplementation function. It is mainly used clinically for fever caused by the common cold or influenza, and is also used to relieve mild to moderate pain, such as headache, joint pain, migraine, toothache, muscle pain, neuralgia, and dysmenorrhea. Summary of the invention

[0007] The purpose of the present invention is to provide an application of carbaspirin calcium in the preparation of a drug for treating hydrocephalus, so as to solve the problem that hydrocephalus can only be treated by surgery which is expensive and has high risks of infection and complications, and to provide an effective candidate drug for treating hydrocephalus, thereby alleviating the pain of treatment for patients and reducing treatment risks and costs.

[0008] To achieve the above object, the present invention provides the use of carbaspirin calcium in the preparation of a drug for treating hydrocephalus, wherein the drug contains carbaspirin calcium as the sole or main active ingredient.

[0009] Preferably, the drug further comprises a pharmaceutically acceptable carrier.

[0010] Preferably, the effective amount of carbaspirin calcium is 75-1000 mg / day.

[0011] Preferably, the effective amount of carbaspirin calcium is 150-500 mg / day.

[0012] Preferably, the carbaspirin calcium is taken orally in the treatment of hydrocephalus.

[0013] Carbaspirin calcium targets MMP9 as a potential therapeutic target for hydrocephalus.

[0014] The present invention uses a zebrafish hydrocephalus model to screen out an active compound, carbaspirin calcium, which can significantly reduce the fourth ventricle area of ​​zebrafish with hydrocephalus and can be used to prevent and / or treat zebrafish hydrocephalus.

[0015] Therefore, the use of carbaspirin calcium provided by the present invention in the preparation of a drug for treating hydrocephalus has the following specific technical effects:

[0016] (1) The present invention first discovered the effect of carbaspirin calcium in treating hydrocephalus, which can significantly reduce the area of ​​the fourth ventricle of hydrocephalus model zebrafish and significantly improve the swimming distance, swimming time, swimming speed and rotational movement frequency of hydrocephalus model zebrafish;

[0017] (2) The experimental data provided by the present invention show that carbaspirin calcium has great application prospects in the treatment of hydrocephalus, and provides an effective candidate drug for alleviating the pain of hydrocephalus patients and reducing treatment risks and costs; and broadens the scope of action of carbaspirin calcium.

[0018] The technical solution of the present invention is further described in detail below through the accompanying drawings and embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings required for use in the description of the embodiments of the present invention will be briefly introduced below. Obviously, the accompanying drawings in the following description are only some embodiments of the present invention. For ordinary technicians in this field, other accompanying drawings can be obtained based on these accompanying drawings without paying creative labor.

[0020] Figure 1 This is a schematic diagram of the experimental process of Example 1 of the present invention;

[0021] Figure 2 The statistical results of the swimming distances of zebrafish fry in different treatment groups developed to 4 dpf in Example 1 of the present invention;

[0022] Figure 3 The swimming speed statistics of zebrafish fry in different treatment groups developed to 4 dpf in Example 1 of the present invention;

[0023] Figure 4 The swimming time statistics of zebrafish fry in different treatment groups developed to 4 dpf in Example 1 of the present invention;

[0024] Figure 5 is the rotational movement frequency of zebrafish fry in different treatment groups in Example 1 of the present invention when they develop to 4 dpf;

[0025] Figure 6 The statistical results of the swimming distances of zebrafish fry in different treatment groups developed to 4 dpf in Example 2 of the present invention;

[0026] Figure 7 The swimming speed statistics of zebrafish fry in different treatment groups in Example 2 of the present invention when they develop to 4 dpf;

[0027] Figure 8 The swimming time statistics of zebrafish fry in different treatment groups developed to 4 dpf in Example 2 of the present invention;

[0028] Fig. 9 is the rotational movement frequency of zebrafish fry in different treatment groups in Example 2 of the present invention when they develop to 4 dpf;

[0029] Fig.10 The statistical results of the swimming distances of zebrafish fry in the blank control group, hydrocephalus group, hydrocephalus+carbaspirin calcium group and carbaspirin calcium group developed to 4 dpf in Example 2 of the present invention;

[0030] Fig.11 The swimming speed statistics of zebrafish fry in the blank control group, hydrocephalus group, hydrocephalus+carbaspirin calcium group and carbaspirin calcium group developed to 4 dpf in Example 2 of the present invention;

[0031] Fig.12 The swimming time statistics of zebrafish fry in the blank control group, hydrocephalus group, hydrocephalus+carbaspirin calcium group and carbaspirin calcium group developed to 4 dpf in Example 2 of the present invention;

[0032] Fig.13 The statistical results of the rotational movement frequency of zebrafish fry in the blank control group, hydrocephalus group, hydrocephalus+carbaspirin calcium group and carbaspirin calcium group in Example 2 of the present invention when they developed to 4 dpf;

[0033] Fig.14 This is a schematic diagram of the experimental process of Example 3 of the present invention;

[0034] Fig.15 Stereo microscope photos of zebrafish larvae in the blank control group (A), hydrocephalus group (B), hydrocephalus + carbaspirin calcium group (C) and carbaspirin calcium group (D) in Example 3 of the present invention;

[0035] Fig.16 The statistical results of the fourth ventricle area of ​​zebrafish juveniles in the blank control group, hydrocephalus group, hydrocephalus+carbaspirin calcium group and carbaspirin calcium group developed to 72 hpf in Example 3 of the present invention;

[0036] Fig.17 The statistical results of the number of apoptotic cells in the fourth ventricle of zebrafish larvae in the blank control group, hydrocephalus group, hydrocephalus+carbaspirin calcium group and carbaspirin calcium group developed to 72 hpf in Example 4 of the present invention;

[0037] Fig.18 A Venn diagram of drug-related targets and hydrocephalus-related targets generated in Example 5 of the present invention;

[0038] Fig.19 The statistical results of the fourth ventricle area of ​​zebrafish fry in the blank control group, hydrocephalus group, hydrocephalus+MMP-9-IN-9 group and MMP-9-IN-9 group developed to 72 hpf in Example 5 of the present invention;

[0039] Fig. 20 These are the statistical results of the fourth ventricle area of ​​zebrafish fry in the blank control group, hydrocephalus group, hydrocephalus+MMP-9-IN-1 group and MMP-9-IN-1 group in Example 5 of the present invention when they developed to 72 hpf. DETAILED DESCRIPTION

[0040] The technical solution of the present invention is further described below through the accompanying drawings and embodiments.

[0041] In order to make the purpose, technical scheme and advantages of the present application clearer, more thorough and more complete, the technical scheme of the present invention is clearly and completely described below through the accompanying drawings and examples. The following detailed descriptions are all descriptions of the embodiments, and are intended to provide further detailed descriptions of the present invention. Unless otherwise specified, all technical terms used in the present invention have the same meaning as those generally understood by those skilled in the art to which the present application belongs.

[0042] The instruments, equipment, reagents and materials used in the examples were all obtained through commercial channels, wherein the zebrafish fry used were zebrafish embryos 6 hours after birth; GRI977143 was purchased from Med Chem Express, carbaspirin calcium was purchased from MedChem Express, tricaine was purchased from SIGMA, PTU was purchased from SIGMA, AO stock solution was purchased from SIGMA, MS-222 was purchased from Med Chem Express, stereo microscope was purchased from Nikon, zebrafish behavior recorder was purchased from Noldus, and upright fluorescence microscope was purchased from OLYMPUS.

[0043] The experimental steps not described in detail in the examples are all routine methods in the art.

[0044] Embodiment 1

[0045] To investigate the effect of carbaspirin calcium on hydrocephalus in zebrafish larvae, the flow chart is as follows Figure 1 As shown, the specific steps are as follows:

[0046] (1) Preparation of zebrafish larvae

[0047] Wild-type zebrafish were obtained from the China Zebrafish Resource Center and maintained at 28±0.5℃, 14h light / 10h dark. Zebrafish embryos were obtained after natural mating of wild-type zebrafish. The obtained zebrafish embryos were washed and stored in E3 culture medium containing 2mg / L methylene blue. The pH of the culture medium was maintained at 7.1, and the culture medium was replaced every day.

[0048] E3 culture medium consists of 5 mM NaCl, 0.17 mM KCl, 0.33 mM CaCl2 and 0.33 mM MgSO4.

[0049] (2) Experimental groups and treatments

[0050] a. Blank control group: zebrafish embryos at 6 hours postnatal (6 hpf) were randomly transferred to a 24-well cell culture plate, with 15 zebrafish embryos per well. 1 mL of E3 culture medium was added so that all 6 hpf zebrafish embryos were in E3 culture medium. The culture medium was replaced every 24 hours.

[0051] b. Hydrocephalus group (Hydro): 6 hpf zebrafish embryos were randomly transferred to a 24-well cell culture plate, with 15 6 hpf zebrafish embryos in each well. Then 5 μg / mL of GRI977143 solution was added to expose all 6 hpf zebrafish embryos to the solution to induce hydrocephalus in zebrafish. The GRI977143 solution was replaced every 24 hours.

[0052] c. Hydrocephalus + carbaspirin calcium group: 6 hpf zebrafish embryos were randomly transferred to a 24-well cell culture plate, with 15 6 hpf zebrafish embryos in each well, and then 5 μg / mL GRI977143 solution was added to expose all 6 hpf zebrafish embryos to the solution. When the embryos developed to 24h (24hpf), carbaspirin calcium solution was added to make the carbaspirin calcium concentrations of 5 μM, 10 μM, and 20 μM, respectively. The concentration of GRI977143 solution was maintained at 5 μg / mL, and the solution was replaced every 24h.

[0053] d. Carbaspirin calcium group: 6 hpf zebrafish embryos were randomly transferred to a 24-well cell culture plate, with 15 6 hpf zebrafish embryos in each well. When the embryos developed to 24h (24hpf), carbaspirin calcium solution was added to make the carbaspirin calcium concentrations 5μM, 10μM, and 20μM, respectively. The solution was replaced every 24h.

[0054] (3) Zebrafish behavioral testing

[0055] When the embryos developed to 72h (72hpf), the zebrafish larvae in each group were subjected to zebrafish behavioral testing. Zebrafish embryos at the 4th day of development (4dpf) were placed in a 48-well plate, one per well, and 1000μL of E3 culture medium was added. After 20min of adaptation using a DanioVision (Noldus) recorder, the data were recorded for 1h with a 10min / 10min light / dark cycle. The statistical results of the swimming distance, swimming time, swimming speed, and rotational movement frequency of 4dpf zebrafish larvae are shown below. Figure 2-5 As shown, the swimming distance, swimming time, swimming speed and rotational movement frequency of zebrafish in the hydrocephalus group were significantly decreased compared with those in the blank control group; after treatment with carbaspirin calcium (20 μM), the swimming distance, swimming time, swimming speed and rotational movement frequency were significantly increased; the swimming distance, swimming time, swimming speed and rotational movement frequency of zebrafish in the carbaspirin calcium group without inducing hydrocephalus were not significantly different from those in the blank control group.

[0056] Embodiment 2

[0057] To investigate the optimal therapeutic concentration of carbaspirin calcium solution, the specific steps are as follows:

[0058] (1) The preparation of zebrafish fry is the same as in Example 1.

[0059] (2) Experimental groups and treatments

[0060] a. Blank control group: zebrafish embryos at 6 hours postnatal (6 hpf) were randomly transferred to a 24-well cell culture plate, with 15 zebrafish embryos per well. 1 mL of E3 culture medium was added so that all 6 hpf zebrafish embryos were in E3 culture medium. The culture medium was replaced every 24 hours.

[0061] b. Hydrocephalus group (Hydro): 6 hpf zebrafish embryos were randomly transferred to a 24-well cell culture plate, with 15 6 hpf zebrafish embryos in each well. Then 5 μg / mL of GRI977143 solution was added to expose all 6 hpf zebrafish embryos to the solution to induce hydrocephalus in zebrafish. The GRI977143 solution was replaced every 24 hours.

[0062] c. Hydrocephalus + carbaspirin calcium group: 6 hpf zebrafish embryos were randomly transferred to a 24-well cell culture plate, with 15 6 hpf zebrafish embryos in each well, and then 5 μg / mL GRI977143 solution was added to expose all 6 hpf zebrafish embryos to the solution. When the embryos developed to 24h (24hpf), carbaspirin calcium solution was added to make the carbaspirin calcium concentrations 10μM, 15μM, 20μM, and 25μM, respectively. The concentration of GRI977143 solution was maintained at 5μg / mL, and the solution was replaced every 24h.

[0063] d. Carbaspirin calcium group: 6 hpf zebrafish embryos were randomly transferred to a 24-well cell culture plate, with 15 6 hpf zebrafish embryos in each well. When the embryos developed to 24 h (24 hpf), carbaspirin calcium solution was added to make the carbaspirin calcium concentrations 10 μM, 15 μM, 20 μM, and 25 μM, respectively. The solution was replaced every 24 h.

[0064] (3) Zebrafish behavioral detection is the same as in Example 1

[0065] The statistical results of swimming distance, swimming time, swimming speed and rotational movement frequency of 4dpf zebrafish larvae are as follows: Figure 6-9 As shown, the swimming distance, swimming time, swimming speed and rotational movement frequency of zebrafish in the hydrocephalus group were significantly decreased compared with those in the blank control group; compared with the zebrafish larvae treated with 10μM, 15μM and 25μM carbaspirin calcium concentrations, the swimming distance, swimming time, swimming speed and rotational movement frequency of zebrafish larvae treated with 20μM carbaspirin calcium increased more significantly; there was no significant difference in the swimming distance, swimming time, swimming speed and rotational movement frequency of zebrafish in the group without inducing hydrocephalus but adding 20μM carbaspirin calcium compared with the blank control group.

[0066] Therefore, the optimal concentration of carbaspirin calcium is 20 μM. The statistical results of the swimming distance, swimming time, swimming speed and rotational movement frequency of zebrafish larvae under the optimal concentration of carbaspirin calcium are as follows: Figure 10-13 shown.

[0067] Embodiment 3

[0068] To image the zebrafish ventricle using a stereomicroscope, follow these steps:

[0069] (1) The preparation of zebrafish fry is the same as in Example 1.

[0070] (2) Experimental grouping and treatment were the same as in Example 2, except that the E3 culture medium was replaced with PTU solution. PTU (phenylthiourea) is a Tyr (tyrosinase) inhibitor that can inhibit the growth of melanin in zebrafish embryos, increase the optical transparency of zebrafish embryos, and facilitate the acquisition of better images under a microscope for research. The concentration of carbaspirin calcium in the hydrocephalus + carbaspirin calcium group and the carbaspirin calcium group was 20 μM.

[0071] (3) Zebrafish ventricle imaging

[0072] When the zebrafish embryos develop to 72h (72hpf), each group of embryos is embedded in low melting point agarose and set aside. After the stereo microscope is debugged, the zebrafish ventricle images are obtained respectively. The flow chart is as follows Fig.14 Some stereo microscope photos are shown in Fig.15 The size of the ventricles was measured using Image J software, and the statistical results of 13 replicates are shown in Fig.16 As shown, the fourth ventricle area of ​​zebrafish in the hydrocephalus group was significantly increased compared with the blank control group; after treatment with carbaspirin calcium, the fourth ventricle area was significantly restored; there was no significant difference in the fourth ventricle area of ​​zebrafish in the group without inducing hydrocephalus but adding carbaspirin calcium compared with the blank control group.

[0073] Embodiment 4

[0074] The number of apoptotic cells in the fourth ventricle of zebrafish was counted using an upright fluorescence microscope. The specific steps are as follows:

[0075] (1) The preparation of zebrafish fry is the same as in Example 1.

[0076] (2) Experimental grouping and treatment are the same as in Example 3.

[0077] (3) Statistical analysis of apoptotic cells in the fourth ventricle of zebrafish

[0078] Acridine orange (AO) is a stain used to identify cell apoptosis. AO stock solution (1 mg / mL, prepared with pure water) was diluted with E3 culture medium at a ratio of 1:200 to a final concentration of 5 μg / mL. Twelve larvae (72 hpf) were randomly selected from different treatment groups, rinsed with E3 culture medium to remove residual exposure solution, and placed in a centrifuge tube. Then 1 mL of diluted AO dye was added and incubated at 28±0.5℃ for 20 minutes and kept in a dark environment to prevent fluorescence quenching. After the incubation, the larvae were washed with E3 solution for 5 minutes to remove the AO dye that did not enter the cells, and then the larvae were anesthetized with 0.01% MS-222 for 3 minutes. The apoptotic cells in the zebrafish were photographed using an upright fluorescence microscope (filter: GFP, wavelength: 470±20 nm). Imaris was used to count the number of apoptotic cells in the fourth ventricle of each larvae. The statistical results of 12 replicates are shown in Figure 2. Fig.17 As shown, the number of apoptotic cells in the fourth ventricle of zebrafish in the hydrocephalus group was significantly increased compared with the blank control group; after treatment with carbaspirin calcium, the number of apoptotic cells decreased; there was no significant difference in the number of apoptotic cells in the fourth ventricle of zebrafish in the group without inducing hydrocephalus but adding carbaspirin calcium compared with the blank control group.

[0079] Embodiment 5

[0080] The specific steps for determining the potential therapeutic target of carbaspirin calcium for hydrocephalus are as follows:

[0081] The keyword "Hydrocephalus" was used to retrieve hydrocephalus-related targets in GeneCards (https: / / www.genecards.org / ), OMIM (https: / / www.omim.org / ), and DisGeNET (https: / / disgenet.com / ). The search results of the three databases were integrated and duplicate gene targets were removed to obtain hydrocephalus-related targets and construct a hydrocephalus disease target library.

[0082] The zebrafish larvae samples from the blank control group and the hydrocephalus group were sent to BioMed for transcriptome sequencing analysis to obtain the differentially expressed genes between the blank control group and the hydrocephalus group and to construct a transcriptome target library.

[0083] Keywords "GRI977143" and "Carbasalatumcalcicum" were used in SwissTargetPrediction (http: / / swisstargetprediction.ch / index.php), PharmMapping (https: / / www.lilab-ecust.cn / pharmmapper / ) and Similarity ensembleapproach (http: / / sea.bkslab.org / ) to retrieve drug-related targets. The search results of the three databases were integrated and duplicate gene targets were removed to obtain drug-related targets. The GRI977143 target library and carbasalatumcalcicum target library were constructed.

[0084] The Venn diagram was generated by importing drug-related targets and hydrocephalus-related targets into the Venny 2.1.0 web platform (https: / / bioinfogp.cnb.csic.es / tools / venny / index.html), as shown in Fig.18 , the search intersection target is mmp9.

[0085] Subsequently, the mmp9 inhibitor was applied to zebrafish larvae to verify whether mmp9 is a therapeutic target of carbaspirin calcium. The specific steps are as follows:

[0086] (1) The preparation of zebrafish fry is the same as in Example 1.

[0087] (2) Experimental grouping and treatment were the same as in Example 2, except that carbaspirin calcium was replaced by mmp9 inhibitors (MMP-9-IN-9, MMP-9-IN-1).

[0088] (3) Imaging of zebrafish ventricles using a stereomicroscope is the same as in Example 3

[0089] Compared with the blank control group, the fourth ventricle area of ​​zebrafish in the hydrocephalus group increased significantly; after the action of MMP inhibitor, the fourth ventricle area was significantly restored. Figure 19-20 .

[0090] Therefore, a potential therapeutic target of carbapenem calcium is MMP9.

[0091] Therefore, the present invention first discovered the effect of carbaspirin calcium in treating hydrocephalus, which can significantly reduce the area of ​​the fourth ventricle of the zebrafish with hydrocephalus model, significantly increase the swimming distance, swimming time, swimming speed, and rotational movement frequency of the zebrafish with hydrocephalus model, and significantly reduce the number of apoptotic cells in the fourth ventricle of the zebrafish with hydrocephalus model; its potential therapeutic target is mmp9. The experimental data provided by the present invention show that carbaspirin calcium has great application prospects in the treatment of hydrocephalus, and provides an effective candidate drug for alleviating the pain of hydrocephalus patients, reducing treatment risks and costs; and broadens the scope of action of carbaspirin calcium.

[0092] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that they can still modify or replace the technical solution of the present invention with equivalents, and these modifications or equivalent replacements cannot cause the modified technical solution to deviate from the spirit and scope of the technical solution of the present invention.

Claims

1. The use of carbaspirin calcium in the preparation of a drug for treating hydrocephalus, characterized in that: The medicine uses carbaspirin calcium as the only or main active ingredient.

2. The use of carbaspirin calcium according to claim 1 in the preparation of a drug for treating hydrocephalus, characterized in that: The medicament further includes a pharmaceutically acceptable carrier.

3. The use of carbaspirin calcium according to claim 1 in preparing a drug for treating hydrocephalus, characterized in that: The effective dosage of carbaspirin calcium is 75-1000 mg / day.

4. The use of carbaspirin calcium according to claim 1 in the preparation of a drug for treating hydrocephalus, characterized in that: The effective dosage of carbaspirin calcium is 150-500 mg / day.

5. The use of carbaspirin calcium according to claim 1 in preparing a drug for treating hydrocephalus, characterized in that: The carbaspirin calcium is taken orally in the treatment of hydrocephalus.

6. The potential therapeutic target of carbaspirin calcium for hydrocephalus is MMP9.

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