Use of nitazoxanide and pharmaceutically acceptable salt thereof in preparation of Anti-adamantinomatous craniopharyngioma drug

Abstract

The present disclosure relates to the technical field of medicines, and in particular relates to the use of nitazoxanide and a pharmaceutically acceptable salt thereof in the preparation of an anti-adamantinomatous craniopharyngioma drug. Provided in the present disclosure is the use of nitazoxanide and a pharmaceutically acceptable salt thereof in the preparation of an anti-adamantinomatous craniopharyngioma drug. Nitazoxanide and the pharmaceutically acceptable salt thereof are capable of inhibiting the proliferation and colony formation ability of adamantinomatous craniopharyngioma organoids by means of promoting the degradation of a β-catenin, are targeted drugs capable of effectively blocking an activation pathway of the β-catenin, have good therapeutic efficacy and application prospects for adamantinomatous craniopharyngioma, and solve the problem of lack of targeted drugs for treating adamantinomatous craniopharyngioma.

Description

Use of nitazoxanide and pharmaceutically acceptable salts thereof in the preparation of a drug for resisting adamantinomatous craniopharyngioma

[0001] Cross-reference to Related Applications

[0002] The present disclosure claims priority to the application No. 2024107364252, filed on June 7, 2024, with the Chinese Patent Office, and entitled "Use of nitazoxanide and pharmaceutically acceptable salts thereof in the preparation of a drug for resisting adamantinomatous craniopharyngioma", the entire content of which is incorporated herein by reference. TECHNICAL FIELD

[0003] The present disclosure relates to the technical field of medicine, in particular to the use of nitazoxanide and pharmaceutically acceptable salts thereof in the preparation of a drug for resisting adamantinomatous craniopharyngioma. BACKGROUND

[0004] Nitazoxanide (NTZ) is a tetrahydrothiazole compound with diverse biological activities. It can effectively resist a variety of intestinal parasites in the human body, including intestinal lamblia, amoeba, cryptosporidium, cyclospora, trichomonas, encephalitozoon intestinal microsporidium, beaver spore ball, human blastocystis, colon pouch, human roundworm, bich intestinal microsporidium, beef tapeworm, short membrane shell tapeworm, micro membrane shell tapeworm, giardia, leishmania, liver fluke, etc.

[0005] Nitazoxanide was first marketed in Mexico in 1996 as an antiparasitic drug, with the English trade name Daxon and Colufas. The U.S. Food and Drug Administration (FDA) approved the drug for the treatment of intestinal protozoan diseases such as cryptosporidiosis and blue giardia lamblia in children aged 1-11 in December 2002, and launched the Alinia oral suspension in the U.S. market.

[0006] The mechanism of action of nitazoxanide against protozoa and anaerobes may be that it inhibits the key enzyme in the anaerobic energy metabolism process, pyruvate ferredoxin oxidoreductase (PFOR). PFOR can catalyze the oxidative dehydrogenation of pyruvate and produce acetyl-CoA and CO2. In structure, NTZ has certain similarity with the cofactor of PFOR, thiamine pyrophosphate (TPP), therefore, NTZ hinders the binding of pyruvate and TPP, further inhibiting the energy metabolism of anaerobic microorganisms and protozoa, thereby playing an anti-protozoan and anaerobic role.

[0007] Currently, adamantinomatous craniopharyngioma (ACP) is a common intracranial tumor in children that occurs in the sellar region, which originates from the degenerated residual craniopharyngeal duct epithelium (also known as Rathke's pouch). At the junction of the tumor and the brain tissue, the tumor epithelium forms "finger-like protrusions" and invades the important neural structures around the hypothalamus, which can cause extensive neurological damage and poor prognosis; the main symptoms of adamantinomatous craniopharyngioma include endocrine dysfunction, visual impairment, and intracranial pressure elevation.

[0008] Adamantinomatous craniopharyngioma has no effective targeted therapeutic drugs, and the main clinical treatment is surgical resection. Due to the special location, high technical requirements, and difficulty in complete removal, postoperative recurrence and serious surgical complications often occur.

[0009] Therefore, the present application is proposed. SUMMARY

[0010] The first object of the present disclosure is to provide a use of nitazoxanide and a pharmaceutically acceptable salt thereof in the preparation of an adamantinomatous craniopharyngioma-resistant drug.

[0011] The second object of the present disclosure is to provide a use of a pharmaceutical composition containing at least one of the drugs nitazoxanide and a pharmaceutically acceptable salt thereof in the preparation of an adamantinomatous craniopharyngioma-resistant drug.

[0012] The third object of the present disclosure is to provide a pharmaceutical preparation.

[0013] In order to achieve the above objects of the present disclosure, the following technical solutions are adopted:

[0014] The present disclosure provides a use of nitazoxanide and a pharmaceutically acceptable salt thereof in the preparation of an adamantinomatous craniopharyngioma-resistant drug.

[0015] Further, the pharmaceutically acceptable salt includes inorganic acid salt and / or organic acid salt.

[0016] Further, the pharmaceutically acceptable salt includes hydrochloride and / or acetate.

[0017] The present disclosure also provides a use of a pharmaceutical composition containing at least one of nitazoxanide and a pharmaceutically acceptable salt thereof in the preparation of an adamantinomatous craniopharyngioma-resistant drug.

[0018] Further, the pharmaceutical composition containing at least one of nitazoxanide and a pharmaceutically acceptable salt thereof further includes a pharmaceutically acceptable excipient.

[0019] Further, the pharmaceutically acceptable excipient includes at least one of a medicinal solvent, a binder, a disintegrant, a flavoring agent, a coloring agent, and a preservative.

[0020] The present disclosure also provides a pharmaceutical preparation including the pharmaceutical composition containing at least one of nitazoxanide and pharmaceutically acceptable salts thereof as described above.

[0021] Further, the pharmaceutical preparation includes an oral preparation and / or an injection preparation.

[0022] Further, the oral preparation includes at least one of a tablet, a capsule, a granule, a pill, and a solution.

[0023] Further, the injection preparation includes at least one of an emulsion type, an oil suspension type, and a water suspension type.

[0024] Compared with the prior art, the present disclosure has the following beneficial effects:

[0025] The present disclosure provides the use of nitazoxanide and pharmaceutically acceptable salts thereof in the preparation of an anti-ameloblastic craniopharyngioma drug, which solves the problem of the lack of targeted drugs for treating ameloblastic craniopharyngioma. Nitazoxanide and pharmaceutically acceptable salts thereof can inhibit the proliferation and clonogenic ability of ameloblastic craniopharyngioma organoids by promoting the degradation of β-catenin (β-catenin), and is a targeted drug that can effectively block the β-catenin activation pathway, and has good therapeutic effect and application prospect for ameloblastic craniopharyngioma. BRIEF DESCRIPTION OF DRAWINGS

[0026] In order to more clearly illustrate the technical solutions of the embodiments of the present disclosure, the following will briefly introduce the drawings needed to be used in the embodiments. It should be understood that the following drawings only show some embodiments of the present disclosure, and therefore should not be considered as limiting the scope. For those skilled in the art, other related drawings can also be obtained from these drawings without creative labor.

[0027] FIG. 1 is a growth situation of ACP organoid tissue culture according to the present disclosure;

[0028] Figure 2 is the identification of ACP organoids tissue culture of the present disclosure; Figure 2A is a HE staining diagram, Figure 2B is a tumor cell Cytokeratin (CK) expression diagram, Figure 2C is a S100 calcium binding protein A8 / A9 (S100A8 / A9), β-catenin and Leukemia inhibitory factor (LIF) co-staining diagram, Figure 2D is a Leukemia inhibitory factor receptor (LIFR) and LIF co-staining diagram, Figure 2E is a CD44 standard subtype (CD44s) expression diagram, and Figure 2F is a CD44 variant subtype (CD44v6) expression diagram.

[0029] Figure 3 is the cell morphology change after nitazoxanide intervention on ACP organoids tissue of the present disclosure.

[0030] Figure 4 is the drug dose-effect curve and cell activity after nitazoxanide intervention on ACP organoids tissue of the present disclosure.

[0031] Figure 5 is the mass spectrum of nitazoxanide and tizoxanide of the present disclosure.

[0032] Figure 6 is the expression of β-catenin in breast cancer cell nucleus and cell activity of breast cancer after 72h intervention of nitazoxanide and tizoxanide of the present disclosure; Figure 6A is the expression of β-catenin in MDA-MB-231 (human) and 4T1 (murine) breast cancer cell nucleus, Figure 6B and 6C are the dose-effect curve and cell activity of MDA-MB-231 (human) breast cancer after 72h intervention of nitazoxanide (NTZ) and tizoxanide (TIZ), and Figure 6D and 6E are the dose-effect curve and cell activity of 4T1 (murine) breast cancer after 72h intervention of nitazoxanide (NTZ) and tizoxanide (TIZ). DETAILED DESCRIPTION

[0033] The technical solutions of the present disclosure will be described clearly and completely in combination with the drawings and specific embodiments, but those skilled in the art will understand that the following described embodiments are part of the embodiments of the present disclosure, not all the embodiments, and are only used to illustrate the present disclosure, and should not be regarded as limiting the scope of the present disclosure. Based on the embodiments in the present disclosure, all other embodiments obtained by those skilled in the art without creative labor are within the scope of protection of the present disclosure. The specific conditions are not specified in the embodiments, and are carried out according to the conventional conditions or the conditions recommended by the manufacturer. The reagents or instruments used are not specified by the manufacturer, and are conventional products that can be purchased on the market.

[0034] The application of nitazoxanide and pharmaceutically acceptable salts thereof in the preparation of an anti-Adamantinomatous craniopharyngioma drug is specifically described below.

[0035] The application of nitazoxanide and pharmaceutically acceptable salts thereof in the preparation of an anti-Adamantinomatous craniopharyngioma (ACP) drug is provided in some embodiments of the present disclosure.

[0036] The chemical formula of nitazoxanide is

[0037] Adamantinomatous craniopharyngioma is a highly inflammatory tumor caused by abnormal activation of the β-catenin pathway induced by Wnt / β-catenin pathway mutations, and is an intracranial tumor that often occurs in the sellar region and often occurs in children.

[0038] The present disclosure provides a targeted drug that can effectively block the activation of the β-catenin pathway based on the targeted treatment of the mutant gene Wnt / β-catenin signal transduction pathway of Adamantinomatous craniopharyngioma.

[0039] Nitazoxanide and pharmaceutically acceptable salts thereof can inhibit the proliferation and clonogenicity of Adamantinomatous craniopharyngioma organoids by promoting the degradation of β-catenin, and nitazoxanide and pharmaceutically acceptable salts thereof have good therapeutic effect and application prospect for Adamantinomatous craniopharyngioma, and provide a targeted drug for treating Adamantinomatous craniopharyngioma.

[0040] In some embodiments of the present disclosure, the pharmaceutically acceptable salt includes an inorganic acid salt and / or an organic acid salt.

[0041] In some embodiments of the present disclosure, the pharmaceutically acceptable salt includes a hydrochloride salt and / or an acetate salt.

[0042] According to the chemical preparation process, clinical medicine and / or pharmacy of nitazoxanide, the pharmaceutically acceptable salt involved in the present disclosure is a salt formed by a non-toxic organic acid or inorganic acid. The term "pharmaceutically acceptable" means that the substance or composition must be suitable for chemistry or toxicology, and related to the composition of the drug.

[0043] The application of a pharmaceutical composition containing at least one of nitazoxanide and pharmaceutically acceptable salts thereof in the preparation of an anti-Adamantinomatous craniopharyngioma drug is also provided in some embodiments of the present disclosure.

[0044] The pharmaceutical composition of the present disclosure refers to a compound group containing one or more than one nitazoxanide and pharmaceutically acceptable salts thereof as an effective ingredient.

[0045] The pharmaceutical composition of the present disclosure can be used for preparing a medicine for treating adamantinomatous craniopharyngioma, and has excellent therapeutic effect on adamantinomatous craniopharyngioma.

[0046] In some embodiments of the present disclosure, the pharmaceutical composition containing at least one of nitazoxanide and pharmaceutically acceptable salts thereof further comprises a pharmaceutically acceptable excipient.

[0047] The pharmaceutically acceptable excipient generally refers to other substances in addition to the active pharmaceutical ingredients in the preparation process of the drug, which includes functional excipients and non-functional excipients. These excipients play an important role in the production, preparation, stability, etc. of the drug.

[0048] In some embodiments of the present disclosure, the pharmaceutically acceptable excipient includes at least one of a pharmaceutical solvent, a binder, a disintegrant, a flavoring agent, a coloring agent, and a preservative.

[0049] The pharmaceutical solvent refers to a solvent required for dissolving or dispersing solids, which plays multiple roles in the preparation process of the pharmaceutical preparation, such as dissolving drugs, diluting solutions, preparing emulsions, suspensions, etc.; including but not limited to water, glycerol, ethanol.

[0050] The binder can make substances adhere together, including but not limited to at least one of hydroxypropyl methylcellulose, sodium carboxymethylcellulose, corn starch, polyvinylpyrrolidone, polyethylene glycol, ethyl cellulose, and polyvinyl alcohol.

[0051] The disintegrant refers to a substance that can break the tablet of the whole substance into many small particles, so as to enable the active ingredient to be rapidly dissolved, absorbed, and quickly act; the disintegrant includes but is not limited to at least one of dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, and cross-linked polyvinylpyrrolidone.

[0052] The flavoring agent refers to a pharmaceutical excipient used to improve or mask the unpleasant odor and taste of the drug, so that the patient cannot easily perceive the strong bitter taste (or other odors such as pungent, irritating, etc.) of the drug; they mainly improve the patient's experience by changing the taste and odor of the drug. The types of flavoring agents are diverse, including sweeteners, aromatic agents, gum agents, and effervescent agents, etc.; the flavoring agent includes but is not limited to at least one of sucrose, monosaccharide syrup, aromatic sugar syrup, and spice.

[0053] The coloring agent is mainly to improve the appearance of the substance, increase the acceptance of the patient, or facilitate the identification of pharmacists, doctors, nurses, and patients when in use. In pharmacy, coloring agents are mainly pigments, including natural pigments and synthetic pigments.

[0054] The preservative is a kind of additive that can prevent or inhibit the growth of microorganisms to ensure the quality of the material. The types of medicinal preservatives include, but are not limited to, at least one of benzoic acid, sodium benzoate, p-hydroxybenzoic acid esters, sorbic acid and potassium sorbate.

[0055] In some embodiments of the present disclosure, a pharmaceutical preparation is also provided, which comprises a pharmaceutical composition containing at least one of nitazoxanide and pharmaceutically acceptable salts thereof; a therapeutic dose of the pharmaceutical preparation of the present disclosure can be effectively administered to a patient to treat the patient's adamantinomatous craniopharyngioma; and the problem of lack of targeted drugs for treating adamantinomatous craniopharyngioma is solved.

[0056] The term "therapeutic dose" refers to the amount of a compound that is sufficient to have an effect on the treatment of a disease when administered to a patient for the treatment of the disease and can vary depending on the compound, the disease and the severity, and the condition, age, weight, gender of the patient to be treated.

[0057] Treatment refers to the improvement of a disease or condition (i.e., slowing or halting the development of the disease or at least one of its clinical symptoms) in a patient by administering to the patient a therapeutic dose of the pharmaceutical preparation of the present disclosure; or,

[0058] Treatment refers to the alleviation or improvement of at least one physical parameter in a patient by administering to the patient a therapeutic dose of the pharmaceutical preparation of the present disclosure, including physical parameters that can not be perceived by the patient; or,

[0059] Treatment refers to the modulation of a disease or condition in a patient physically (e.g., stabilizing a perceived symptom) or physiologically (e.g., stabilizing a parameter of the body) or both by administering to the patient a therapeutic dose of the pharmaceutical preparation of the present disclosure; or,

[0060] Treatment refers to the prevention or delay of the onset, occurrence or aggravation of a disease or condition in a patient by administering to the patient a therapeutic dose of the pharmaceutical preparation of the present disclosure.

[0061] In some embodiments of the present disclosure, the pharmaceutical preparation comprises an oral preparation and / or an injection preparation.

[0062] In some embodiments of the present disclosure, the oral preparation comprises at least one of tablets, capsules, granules, pills and solutions.

[0063] In some embodiments of the present disclosure, the injection preparation comprises at least one of emulsion type, oil suspension type and water suspension type.

[0064] The use of the pharmaceutical preparation involved in the present disclosure is described below.

[0065] The pharmaceutical preparation of the present disclosure is applied to a method for using against adamantinomatous craniopharyngioma, and the method is to administer the pharmaceutical preparation including a pharmaceutical composition containing a therapeutic dose of at least one of nitazoxanide and a pharmaceutically acceptable salt thereof to a patient's affected site.

[0066] The pharmaceutical preparation of the present disclosure can be manufactured according to the conventional methods in the field of the present technology disclosed, and the pharmaceutical preparation is a target dosage form suitable for the purpose of treatment. Nitazoxanide and a pharmaceutically acceptable salt thereof are administered in different dosage forms with suitable pharmaceutically acceptable excipients selected according to the form of administration and conventional pharmaceutical practice.

[0067] The pharmaceutical oral preparation is used for the treatment of adamantinomatous craniopharyngioma, including but not limited to oral preparations such as tablets, capsules, granules, pills, solutions, and the pharmaceutical preparation of the present disclosure is administered to a patient in the form of oral administration.

[0068] The pharmaceutical injection preparation is used for the treatment of adamantinomatous craniopharyngioma, including but not limited to injection preparations such as emulsion type, oil suspension type, and water suspension type, and the pharmaceutical preparation is injected into a patient by a professional technician using injection equipment.

[0069] The administration regimen of the pharmaceutical preparation of the present disclosure will vary depending on various known factors, such as the pharmacokinetic characteristics of the specific agent and its mode and route of administration; the species, age, and body weight of the patient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; the route of administration; and the therapeutic effect desired. A physician can make a decision and prescribe an effective amount of the drug to prevent, arrest, alleviate, or slow the development of symptoms of the disease.

[0070] Test Example 1

[0071] Adamantinomatous craniopharyngioma (ACP) organoid culture and identification:

[0072] The ACP tissue sample was cleaned with pre-cooled PBS to remove the residual preservative solution, and red blood cell lysis solution was used to digest and clean for 5 min to remove blood; the tumor tissue was cut into 1-3 mm 3Small pieces of ACP tissue were added with 5 mL of tumor tissue digestion solution and mixed well, and then placed in a constant temperature shaker at 37°C and 100 rpm for digestion; when a large number of dissociated cell clusters were observed under a microscope, the digestion was terminated by adding an equal volume of 5% FBS-containing organoid culture solution; the cell suspension was filtered with a cell strainer and centrifuged at 4°C and 250g for 5 min, and the supernatant was removed; the concentrated cell suspension and Matrigel were mixed well at a ratio of 1:4 (vol / vol), and 50 μL of the mixture was inoculated into each well of a 24-well cell culture plate, and then incubated at 37°C and 5% CO2 for 30 min; after the Matrigel droplet solidified, 500 μL of craniopharyngioma organoid culture medium was carefully added along the wall of the well, and then placed in a CO2 incubator for culture; the culture medium was replaced every 3 days, and the growth of the organoids was observed. The growth of the ACP organoid tissue culture is shown in FIG. 1.

[0073] After successful subculture, the ACP organoid tissue was subjected to hematoxylin-eosin (HE) and fluorescence staining of related indicators, and the results are shown in FIG. 2. FIG. 2A is an HE staining diagram, FIG. 2B is a tumor cell keratin (Cytokeratin, CK) expression diagram, FIG. 2C is a co-staining diagram of S100 calcium-binding protein A8 / A9 (S100A8 / A9), β-catenin and leukemia inhibitory factor (Leukemia inhibitory factor, LIF), FIG. 2D is a co-staining diagram of leukemia inhibitory factor receptor (Leukemia inhibitory factor receptor, LIFR) and LIF, FIG. 2E is a CD44 standard subtype (CD44s) expression diagram, and FIG. 2F is a CD44 variant subtype (CD44v6) expression diagram.

[0074] As can be seen from FIG. 2, the characteristic structural cell clusters, wet keratin, calcified crystals and palisade epithelium (PE) consistent with the ACP tissue are embodied; the co-staining of CK, S100A8 / A9, β-catenin and LIF, the co-staining of LIFR and LIF, and the expression of CD44s and CD44v6 are also embodied.

[0075] Nitazoxanide was purchased from MedChemExpress, USA, with a purity of 99.95%, and was prepared into a 10 mM stock solution with DMSO and stored at -20 degrees. Before use, the 10 mM nitazoxanide stock solution was diluted to 2 mM, 1 mM, 500 μM, 250 μM, and 125 μM with the ACP organoid culture solution. The above diluted nitazoxanide stock solution was added to the organoid suspension at a ratio of 1:9, i.e. the intervention concentration of nitazoxanide was 200 μM, 100 μM, 50 μM, 50 μM, 25 μM, and 12.5 μM. After intervention of the ACP organoid culture tissue, the cell activity of each intervention concentration group was detected, and the dose-effect curve of nitazoxanide was drawn, as shown in Figures 3 and 4. Figure 3 shows the cell morphological changes of ACP organoid tissue after 48 h, 72 h, and 96 h of intervention with nitazoxanide. Figure 4A shows the drug dose-effect curve of ACP organoid tissue after 96 h of intervention with nitazoxanide, and Figure 4B shows the cell activity of ACP organoid tissue after 96 h of intervention with nitazoxanide (NTZ: P < 0.001 vs Control). *** P < 0.001 vs Control.

[0076] As can be seen from Figure 4, nitazoxanide can effectively reduce the cell activity of ACP organoid tissue.

[0077] Nitazoxanide is metabolized into tizoxanide (TIZ) in vivo to exert its effect. We established an LC-MS / MS method to determine the concentration of nitazoxanide and TIZ in the organoid culture solution, and the results are shown in Figure 5. Figure 5A is the mass spectrum of nitazoxanide, and Figure 5B is the mass spectrum of tizoxanide. The results of Figure 5 show that NTZ can also be converted into TIZ in the organoid culture solution and play a role in inhibiting ACP organoids.

[0078] To determine whether nitazoxanide has drug properties in ACP, we selected breast cancer without the β-catenin pathway as the control group, and the results are shown in Figure 6. Figure 6A shows the expression of β-catenin in the nuclei of MDA-MB-231 (human) and 4T1 (murine) breast cancer cells. Figure 6B and C show the dose-effect curve and cell activity of MDA-MB-231 (human) breast cancer after 72 h of intervention with nitazoxanide (NTZ) and tizoxanide (TIZ) (NTZ: P < 0.05, * P < 0.05, *** P < 0.001, **** P < 0.0001 vs Control; TIZ: P < 0.05, # P < 0.05, #### P < 0.0001 vs Control), and Figure 6D and E show the dose-effect curve and cell activity of 4T1 (murine) breast cancer cells after 72 h of intervention with nitazoxanide (NTZ) and tizoxanide (TIZ) (NTZ: P < 0.05,* P<0.05, **** P < 0.0001 vs Control; TIZ: ## P<0.01, ### P < 0.001 (vs Control).

[0079] As shown in Figure 6, no β-catenin accumulation was observed in the nuclei of MDA-MB-231 (human) and 4T1 (mouse) breast cancer cells, indicating the absence of β-catenin pathway aggregation in the nuclei of these breast cancer cells. NTZ's effect on the IC50 of MDA-MB-231 (human) and 4T1 (mouse) cells at 72 h was also discussed. 50 The values ​​were 73.94 μM and 111.5 μM, respectively; the IC50 values ​​of TIZ on MDA-MB-231 (human) and 4T1 (mouse) cells at 72 h were... 50 The values ​​were 47.47 μM and 143.7 μM, respectively. However, in studies targeting ACP organoids, NTZ showed a lower IC50 concentration after 96 hours of treatment. 50 The value was 24.77 μM, which reveals that nitrozonide has high sensitivity to craniopharyngioma cells.

[0080] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this disclosure, and are not intended to limit them. Although this disclosure has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this disclosure. Industrial applicability

[0081] This disclosure provides the use of nitrozonide and its pharmaceutically acceptable salts in the preparation of drugs for ameloblastic craniopharyngioma. Nitrozonide and its pharmaceutically acceptable salts can inhibit the proliferation and colony formation of ameloblastic craniopharyngioma organoids by promoting the degradation of β-catenin. It is a targeted drug that can effectively block the β-catenin activation pathway and has good therapeutic effects and application prospects for ameloblastic craniopharyngioma, and has good industrial applicability.

Claims

1. Use of nitazoxanide and a pharmaceutically acceptable salt thereof in the preparation of a medicine for resisting adamantinomatous craniopharyngioma.

2. Use according to claim 1, characterized in that, The pharmaceutically acceptable salt includes an inorganic acid salt and / or an organic acid salt.

3. Use according to claim 1 or 2, characterized in that, The pharmaceutically acceptable salt includes a hydrochloride and / or an acetate.

4. Use of a pharmaceutical composition containing at least one of nitazoxanide and a pharmaceutically acceptable salt thereof in the preparation of a medicine for resisting adamantinomatous craniopharyngioma.

5. Use according to claim 4, characterized in that, The pharmaceutical composition containing at least one of nitazoxanide and a pharmaceutically acceptable salt thereof further includes a pharmaceutically acceptable excipient.

6. Use according to claim 5, characterized in that, The pharmaceutically acceptable excipient includes at least one of a medicinal solvent, a binder, a disintegrant, a flavoring agent, a coloring agent, and a preservative.

7. A pharmaceutical preparation, characterized by, The pharmaceutical composition containing at least one of nitazoxanide and a pharmaceutically acceptable salt thereof according to any one of claims 4 to 6.

8. The pharmaceutical preparation according to claim 7, characterized in that, The pharmaceutical preparation includes an oral preparation and / or an injection preparation.

9. The pharmaceutical preparation according to claim 8, characterized in that, The oral preparation includes at least one of a tablet, a capsule, a granule, a pill, and a solution.

10. The pharmaceutical preparation according to claim 8 or 9, characterized in that, The injection preparation includes at least one of an emulsion type, an oil suspension type, and a water suspension type.

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