Application of nitazoxanide and pharmaceutically acceptable salt thereof in preparation of glazed cell type craniopharyngeal tubuloma resisting medicine

Abstract

The invention relates to the technical field of medicine, in particular to application of nitazoxanide and pharmaceutically acceptable salt thereof in preparation of a medicine for resisting glazing cell type craniopharyngeal tubuloma. The invention provides application of nitazoxanide and pharmaceutically acceptable salt thereof in preparation of a medicine for resisting glazing cell type craniopharyngeal tubuloma. The nitazoxanide and the pharmaceutically acceptable salt thereof can inhibit proliferation and clone formation ability of glazed cell type craniopharyngeal tubuloma organs by promoting degradation of beta-catenin, and are targeted drugs capable of effectively preventing a beta-catenin activation pathway. The pharmaceutical composition has a good treatment effect and application prospect on the glazed cell type craniopharyngeal tubuloma, and solves the problem of lack of targeted drugs for treating the glazed cell type craniopharyngeal tubuloma.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and in particular to the use of nitazoxanide and its pharmaceutically acceptable salts in the preparation of drugs for treating adamantinomatous craniopharyngioma. Background Art

[0002] Nitazoxanide (NTZ) is a tetrahydrothiazole compound with diverse biological activities. It can effectively combat a variety of intestinal parasites in the human body, specifically including: Giardia lamblia, Entamoeba histolytica, Cryptosporidium parvum, Cyclospora cayetanensis, Trichomonas vaginalis, Encephalitozoon intestinalis, Sphaerospora beckeri, Blastocystis hominis, Balantidium coli, Ascaris lumbricoides, Enterocytozoon bieneusi, Taenia saginata, Hymenolepis nana, Hymenolepis diminuta, Giardia, Leishmania, Fasciola hepatica, etc.

[0003] Nitazoxanide was first marketed as an anti-parasitic drug in Mexico in 1996, with the English trade names Daxon and Colufas. The US Food and Drug Administration (FDA) approved the drug for the treatment of intestinal protozoal diseases such as cryptosporidiosis and giardiasis in children aged 1 to 11 years in December 2002, and it was launched in the US market under the trade name Alinia oral suspension.

[0004] The mechanism of action of nitazoxanide against protozoa and anaerobic bacteria may be that it inhibits the key enzyme in the anaerobic energy metabolism process - pyruvate ferredoxin oxidoreductase (PFOR); ferredoxin oxidoreductase PFOR, PFOR can catalyze the oxidative dehydrogenation of pyruvate and produce acetyl coenzyme A and CO 2 , in terms of structure, NTZ has a certain similarity to the cofactor thiamine pyrophosphate (TPP) of PFOR. Therefore, NTZ hinders the binding of pyruvate to TPP, further inhibiting the energy metabolism of anaerobic microorganisms and protozoa, etc., thereby exerting the effects of anti-protozoa and anaerobic bacteria.

[0005] Currently, adamantinomatous craniopharyngioma (ACP) is a common intracranial tumor in children that occurs in the sellar region and 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 projections" and invades important nerve structures around the hypothalamus, which may cause extensive nervous system damage and poor prognosis; the main symptoms of adamantinomatous craniopharyngioma include endocrine dysfunction, visual impairment, and increased intracranial pressure.

[0006] There are no effective targeted therapeutic drugs for ameloblastic craniopharyngioma. Clinically, surgical resection is mainly used. Due to the special location, the surgical technique requirements are high, it is not easy to completely remove, and recurrence often occurs easily after surgery, and the surgical complications are serious.

[0007] In view of this, this invention is specifically proposed. Summary of the Invention

[0008] The first object of the present invention is to provide the use of nitazoxanide and its pharmaceutically acceptable salts in the preparation of drugs for treating ameloblastic craniopharyngioma.

[0009] The second object of the present invention is to provide the use of a pharmaceutical composition containing at least one of nitazoxanide and its pharmaceutically acceptable salts in the preparation of drugs for treating ameloblastic craniopharyngioma.

[0010] The third object of the present invention is to provide a pharmaceutical preparation.

[0011] In order to achieve the above objects of the present invention, the following technical solutions are specifically adopted:

[0012] The present invention provides the use of nitazoxanide and its pharmaceutically acceptable salts in the preparation of drugs for treating ameloblastic craniopharyngioma.

[0013] Further, the pharmaceutically acceptable salts include inorganic acid salts and / or organic acid salts.

[0014] Further, the pharmaceutically acceptable salts include hydrochloride salts and / or acetate salts.

[0015] The present invention also provides the use of a pharmaceutical composition containing at least one of nitazoxanide and its pharmaceutically acceptable salts in the preparation of drugs for treating ameloblastic craniopharyngioma.

[0016] Further, the pharmaceutical composition containing at least one of nitazoxanide and its pharmaceutically acceptable salts further includes pharmaceutically acceptable excipients.

[0017] Further, the pharmaceutically acceptable excipients include at least one of pharmaceutical solvents, binders, disintegrants, flavoring agents, coloring agents, and preservatives.

[0018] The present invention also provides a pharmaceutical preparation, including the pharmaceutical composition containing at least one of nitazoxanide and its pharmaceutically acceptable salts as described above.

[0019] Further, the pharmaceutical preparation includes oral preparations and / or injection preparations.

[0020] Further, the oral preparations include at least one of tablets, capsules, granules, pills, and solutions.

[0021] Furthermore, the injection preparation includes at least one of an emulsion type, an oil suspension type, and a water suspension type.

[0022] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0023] The application of nitazoxanide and its pharmaceutically acceptable salts provided by the present invention in the preparation of drugs for treating ameloblastic craniopharyngioma solves the problem of the lack of targeted drugs for treating ameloblastic craniopharyngioma; nitazoxanide and its pharmaceutically acceptable salts can inhibit the proliferation and clonogenic ability of ameloblastic craniopharyngioma organoids by promoting the degradation of β-catenin, and 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. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following will briefly introduce the drawings required for the embodiments. It should be understood that the following drawings only show some embodiments of the present invention, and therefore should not be regarded as limiting the scope. For those of ordinary skill in the art, other related drawings can be obtained based on these drawings without creative efforts.

[0025] Figure 1 It is the growth situation of the ACP organoid tissue culture of the present invention;

[0026] Figure 2 It is the identification situation of the ACP organoid tissue culture of the present invention; Figure 2 In which A is the HE staining picture, Figure 2 In which B is the expression picture of cytokeratin (CK) of tumor cells, Figure 2 In which C is the co-staining picture of S100 calcium-binding protein A8 / A9 (S100A8 / A9), β-catenin and leukemia inhibitory factor (LIF), Figure 2 In which D is the co-staining picture of leukemia inhibitory factor receptor (LIFR) and LIF, Figure 2 In which E is the expression picture of CD44 standard subtype (CD44s), Figure 2 In which F is the expression picture of CD44 variant subtype (CD44v6);

[0027] Figure 3 It is the cell morphological changes after the ACP organoid tissue is intervened by nitazoxanide of the present invention;

[0028] Figure 4This is the drug dose-effect curve (A) and cell viability (B) after nitazoxanide intervention on ACP organoids in the present invention;

[0029] Figure 5 This is the mass spectrum of nitazoxanide (A) and the mass spectrum of tizoxanide (B) in the present invention;

[0030] Figure 6 This is the expression of β-catenin in the nucleus of breast cancer cells in the present invention and the cell viability of breast cancer after 72 h of intervention with nitazoxanide and tizoxanide; Figure 6 In A, it is the expression of β-catenin in the nucleus of MDA-MB-231 (human-derived) and 4T1 (mouse-derived) breast cancer cells, Figure 6 In B and C, they are the dose-effect curve and cell viability of MDA-MB-231 (human-derived) breast cancer after 72 h of treatment with nitazoxanide (NTZ) and tizoxanide (TIZ), Figure 6 In D and E, they are the dose-effect curve and cell viability of 4T1 (mouse-derived) breast cancer cells after 72 h of treatment with nitazoxanide (NTZ) and tizoxanide (TIZ). Detailed implementation manners

[0031] The technical solutions of the present invention will be clearly and completely described below in conjunction with the accompanying drawings and specific implementation manners. However, those skilled in the art will understand that the following described embodiments are some embodiments of the present invention, rather than all embodiments, and are only used to illustrate the present invention and should not be regarded as limiting the scope of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts belong to the scope of protection of the present invention. For those conditions not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. For reagents or instruments not specified by the manufacturer, they are all conventional products that can be obtained through commercial purchase.

[0032] The application of a nitazoxanide and its pharmaceutically acceptable salts in the preparation of drugs for treating adamantinomatous craniopharyngioma (ACP) of the present invention will be specifically described below.

[0033] In some embodiments of the present invention, there is provided an application of a nitazoxanide and its pharmaceutically acceptable salts in the preparation of drugs for treating adamantinomatous craniopharyngioma (ACP).

[0034] The chemical formula of nitazoxanide is

[0035] Adamantinomatous craniopharyngioma is a highly inflammatory tumor caused by single-gene mutations induced by the Wnt / β-catenin pathway, leading to abnormal activation of the β-catenin pathway. It is an intracranial tumor that commonly occurs in the sellar region and is more prevalent in children.

[0036] Based on the targeted therapy of the mutant gene Wnt / β-catenin signal transduction pathway in adamantinomatous craniopharyngioma, the present invention provides a targeted drug that can effectively block the β-catenin activation pathway.

[0037] Nitazoxanide and its pharmaceutically acceptable salts can inhibit the proliferation and clonogenic ability of the organoids of adamantinomatous craniopharyngioma by promoting the degradation of β-catenin. Nitazoxanide and its pharmaceutically acceptable salts have good therapeutic effects and application prospects for adamantinomatous craniopharyngioma, providing a targeted drug for the treatment of adamantinomatous craniopharyngioma.

[0038] In some embodiments of the present invention, the pharmaceutically acceptable salts include inorganic acid salts and / or organic acid salts.

[0039] In some embodiments of the present invention, the pharmaceutically acceptable salts include hydrochloride salts and / or acetate salts.

[0040] According to the chemical preparation process, clinical medicine, and / or pharmaceutical needs of nitazoxanide, the pharmaceutically acceptable salts involved in the present invention are salts formed from non-toxic organic acids or inorganic acids. The term "pharmaceutically acceptable" means that the substance or composition must be suitable chemically or toxicologically and is related to the composition of the drug.

[0041] In some embodiments of the present invention, there is also provided the use of a pharmaceutical composition containing at least one of nitazoxanide and its pharmaceutically acceptable salts in the preparation of a drug for treating adamantinomatous craniopharyngioma.

[0042] The pharmaceutical composition of the present invention refers to a collective of compounds containing one or more of nitazoxanide and its pharmaceutically acceptable salts as active ingredients.

[0043] The pharmaceutical composition of the present invention can be used to prepare a drug for treating adamantinomatous craniopharyngioma and has excellent therapeutic effects on adamantinomatous craniopharyngioma.

[0044] In some embodiments of the present invention, the pharmaceutical composition containing at least one of nitazoxanide and its pharmaceutically acceptable salts further includes pharmaceutically acceptable excipients.

[0045] Pharmaceutically acceptable excipients generally refer to other substances in the preparation of drugs, in addition to the active pharmaceutical ingredients. They include functional excipients and non-functional excipients. These excipients play important roles in the production, preparation, stability, etc. of drugs.

[0046] In some embodiments of the present invention, the pharmaceutically acceptable excipients include at least one of medicinal solvents, binders, disintegrants, flavoring agents, coloring agents, and preservatives.

[0047] A medicinal solvent refers to a solvent required to dissolve or disperse solids, and plays various roles in the preparation of pharmaceutical preparations, such as dissolving drugs, diluting solutions, preparing emulsions, suspensions, etc.; it includes but is not limited to water, glycerol, and ethanol.

[0048] Binders can bond substances together, and include at least one of hydroxypropyl methylcellulose, sodium carboxymethylcellulose, corn starch, polyvinylpyrrolidone, polyethylene glycol, ethyl cellulose, and polyvinyl alcohol.

[0049] A disintegrant refers to a substance that can break a whole sheet-like substance into many fine particles, so that the active ingredient can be quickly dissolved, absorbed, and quickly play its role; disintegrants include but are not limited to at least one of dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, and cross-linked polyvinylpyrrolidone.

[0050] Flavoring agents are pharmaceutically acceptable excipients used to improve or mask the unpleasant odor and taste of drugs, making it difficult for patients to detect the strong bitter taste (or other unpleasant odors such as spicy, irritating, etc.) of the drugs; they mainly improve the patient's medication experience by changing the taste and smell of the drugs. There are various types of flavoring agents, including sweeteners, aromatics, mucilages, and effervescent agents, etc.; flavoring agents include but are not limited to at least one of sucrose, simple syrup, aromatic syrup, and spices.

[0051] Coloring agents are mainly used to improve the appearance of substances, increase the acceptance of patients, or facilitate identification by pharmacists, physicians, nurses, and patients during use. In pharmacy, coloring agents are mostly pigments, including natural pigments and synthetic pigments.

[0052] Preservatives are a class of additives that can prevent or inhibit the growth of microorganisms to ensure the quality of substances; there are many types of medicinal preservatives, including but not limited to at least one of benzoic acid, sodium benzoate, p-hydroxybenzoate esters, sorbic acid, and potassium sorbate.

[0053] In some embodiments of the present invention, a pharmaceutical preparation is also provided, which comprises a pharmaceutical composition containing at least one of nitazoxanide and its pharmaceutically acceptable salts; administering a therapeutic dose of the pharmaceutical preparation of the present invention to a patient can effectively treat the patient with ameloblastic craniopharyngioma; and the problem of lack of targeted drugs for treating ameloblastic craniopharyngioma is solved.

[0054] The term "therapeutic dose" refers to the amount of a compound that is sufficient to be effective in treating a disease when administered to a patient for treating the disease and can vary with the compound, the disease and its severity, and the condition, age, weight, and sex of the patient to be treated.

[0055] Treatment means administering a therapeutic dose of the pharmaceutical preparation of the present invention to a patient to improve a disease or disorder (i.e., slow down or arrest or alleviate the development of the disease or at least one of its clinical symptoms); or,

[0056] Treatment means administering a therapeutic dose of the pharmaceutical preparation of the present invention to a patient to mitigate or improve at least one physical parameter, including physical parameters that may not be perceptible to the patient; or,

[0057] Treatment means administering a therapeutic dose of the pharmaceutical preparation of the present invention to a patient to regulate a disease or disorder physically (e.g., stabilizing perceptible symptoms) or physiologically (e.g., stabilizing physical parameters) or both; or,

[0058] Treatment means administering a therapeutic dose of the pharmaceutical preparation of the present invention to a patient to prevent or delay the onset, occurrence, or worsening of a disease or disorder.

[0059] In some embodiments of the present invention, the pharmaceutical preparation includes an oral preparation and / or an injection preparation.

[0060] In some embodiments of the present invention, the oral preparation includes at least one of tablets, capsules, granules, pills, and solutions.

[0061] In some embodiments of the present invention, the injection preparation includes at least one of an emulsion type, an oil suspension type, and a water suspension type.

[0062] The usage method of the pharmaceutical preparation related to the present invention will be described below.

[0063] The usage method of the pharmaceutical preparation of the present invention in the treatment of ameloblastic craniopharyngioma is: administering to the diseased part of the patient a pharmaceutical preparation comprising a pharmaceutical composition containing at least one of a therapeutic dose of nitazoxanide and its pharmaceutically acceptable salts.

[0064] The pharmaceutical preparation of the present invention can be manufactured according to conventional methods in the disclosed technical field, and the pharmaceutical preparation is a target dosage form suitable for therapeutic purposes. Nitazoxanide and its pharmaceutically acceptable salts are administered in different dosage forms with suitable pharmaceutically acceptable excipients selected according to the form of administration and conventional pharmaceutical practice.

[0065] The oral pharmaceutical preparations are used for the treatment of ameloblastic craniopharyngioma, including but not limited to oral preparations such as tablets, capsules, granules, pills, and solutions. The pharmaceutical preparation of the present invention is administered to patients in the oral form.

[0066] The injectable pharmaceutical preparations are used for the treatment of ameloblastic craniopharyngioma, including but not limited to injectable preparations such as emulsions, oil suspensions, and aqueous suspensions. The pharmaceutical preparation is injected into the patient by a professional using injection-specific equipment.

[0067] The dosing regimen of the pharmaceutical preparation of the present invention will vary with various known factors, such as the pharmacokinetic characteristics of the specific agent, its mode and route of administration; the type, age, and weight of the patient; the nature and degree of the symptoms; the type of concurrent treatment; the frequency of the therapeutic drug; the route of administration and the desired therapeutic effect. A doctor can make a decision and prescribe an effective amount of the drug to prevent, arrest, alleviate, or slow down the development of the disease symptoms.

[0068] Test Example 1

[0069] Culture and identification of ameloblastic craniopharyngioma (ACP) organoids:

[0070] The residual preservation solution of the ACP tissue sample was removed with pre-cooled PBS, and the blood was removed by digestion and washing with red blood cell lysate for 5 min; the tumor tissue was cut into small pieces of 1 - 3 mm 3 , 5 mL of tumor tissue digestive solution was added and mixed evenly, and it was placed in a constant temperature shaker at 37 °C and 100 rpm for oscillating digestion; when a large number of dissociated cell clusters could be observed under microscopy in the digestion supernatant, an equal volume of organoid culture medium containing 5% FBS was added to terminate the digestion; the cell suspension was filtered through a cell sieve and collected, centrifuged at 4 °C and 250 g for 5 min, and the supernatant was removed; the concentrated cell suspension and Matrigel were thoroughly mixed at a ratio of 1:4 (vol / vol), and inoculated into a 24-well cell culture plate at a dose of 50 μL per well, and incubated at 37 °C and 5% CO2 for 30 min; after the Matrigel droplet solidified, 500 μL of craniopharyngioma organoid medium was carefully added along the well wall, and it was placed back into the CO 2 incubator for culture; the culture medium was renewed every 3 days, and the growth of organoids could be seen. The growth of ACP organoid tissue culture is as Figure 1 shown.

[0071] After successful passage, hematoxylin and eosin (HE) staining and fluorescence staining of related indicators were performed on ACP organoid tissues, and the results are as Figure 2 shown. Figure 2 In [Figure], A is the HE staining image, Figure 2 in which B is the expression image of cytokeratin (CK) in tumor cells, Figure 2 in which C is the co-staining image of S100 calcium-binding protein A8 / A9 (S100A8 / A9), β-catenin and leukemia inhibitory factor (LIF), Figure 2 in which D is the co-staining image of leukemia inhibitory factor receptor (LIFR) and LIF, Figure 2 in which E is the expression image of CD44 standard isoform (CD44s), Figure 2 in which F is the expression image of CD44 variant isoform (CD44v6).

[0072] It can be seen from Figure 2 that characteristic structural cell clusters (Cell cluster), wet keratin, calcified crystals and palisade epithelium (PE) consistent with ACP tissues are also shown; 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 demonstrated.

[0073] Nitazoxanide was purchased from MedChemExpress, USA, with a purity of 99.95%. It was prepared into a 10 mM stock solution using DMSO and stored at -20 °C. Before use, the 10 mM nitazoxanide stock solution was diluted to concentrations of 2 mM, 1 mM, 500 μM, 250 μM, and 125 μM with ACP organoid culture medium. The diluted nitazoxanide stock solution was added to the organoid suspension at a ratio of 1:9, that is, the intervention concentrations of nitazoxanide were: 200 μM, 100 μM, 50 μM, 50 μM, 25 μM, and 12.5 μM. After intervening in ACP organoid culture tissues, the cell viability of each intervention concentration group was detected, and a dose-effect curve of nitazoxanide was plotted. The results are as Figure 3 and Figure 4 shown. Figure 3 are the cell morphological changes of ACP organoid tissues intervened with nitazoxanide for 48 h, 72 h, and 96 h. Figure 4 In [Figure], A is the drug dose-effect curve of ACP organoid tissues intervened with nitazoxanide for 96 h, Figure 4 in which B is the cell viability ( ***P < 0.001 vs Control).

[0074] From Figure 4 It can be seen that nitazoxanide can effectively reduce the cell viability of ACP organoids.

[0075] Nitazoxanide is metabolized in vivo to tizoxanide (TIZ) and exerts its effect. By establishing LC-MS / MS to measure the concentrations of nitazoxanide and TIZ in the organoid culture medium, the results are as Figure 5 shown. Figure 5 In which A is the mass spectrum of nitazoxanide, Figure 5 and B in it is the mass spectrum of tizoxanide.

[0076] From Figure 5 It can be seen that in the organoid culture medium, NTZ can also be converted into TIZ and play a role in inhibiting ACP organoids.

[0077] To determine the druggability of nitazoxanide in ACP, breast cancer without the β-catenin pathway was selected as the control group, and the results are as Figure 6 shown. Figure 6 In which A shows the expression of β-catenin in the nuclei of MDA-MB-231 (human) and 4T1 (mouse) breast cancers, Figure 6 and B and C in it show the dose-response curves and cell viability of MDA-MB-231 (human) breast cancer after 72 h of treatment with nitazoxanide (NTZ) and tizoxanide (TIZ) (NTZ: * P < 0.05, *** P < 0.001, **** P < 0.0001 vs Control; TIZ: # P < 0.05, #### P < 0.0001 vs Control), Figure 6 and D and E in it show the dose-response curves and cell viability of 4T1 (mouse) breast cancer cells after 72 h of treatment with nitazoxanide (NTZ) and tizoxanide (TIZ) (NTZ: * P < 0.05, **** P < 0.0001 vs Control; TIZ: ## P < 0.01, ### P < 0.001 vs Control).

[0078] From Figure 6It can be seen that there is no β-catenin accumulation in the nuclei of MDA-MB-231 (human-derived) and 4T1 (mouse-derived) breast cancer cells, indicating that there is no aggregation of the β-catenin pathway in the nuclei of this breast cancer. The IC50 values of NTZ for MDA-MB-231 (human-derived) and 4T1 (mouse-derived) cells at 72 h were 73.94 μM and 111.5 μM, respectively; the IC50 values of TIZ for MDA-MB-231 (human-derived) and 4T1 (mouse-derived) cells at 72 h were 47.47 μM and 143.7 μM, respectively. However, in the study on ACP organoids, the IC50 value of NTZ after 96 h of action was 24.77 μM, which revealed that nitazoxanide has a high sensitivity to craniopharyngioma cells.

[0079] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present disclosure, and are not intended to limit them; although the present disclosure has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements on some or all of the technical features; and these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present disclosure.

Claims

1. Use of nitazoxanide and a pharmaceutically acceptable salt thereof in the preparation of an anti-ameloblastic craniopharyngioma drug.

2. The use according to claim 1, characterized in that: The pharmaceutically acceptable salts include inorganic acid salts and / or organic acid salts.

3. The use according to claim 1, characterized in that: The pharmaceutically acceptable salts include hydrochloride and / or acetate.

4. Use of a pharmaceutical composition containing at least one of nitazoxanide and a pharmaceutically acceptable salt thereof in the preparation of a drug for treating ameloblastic craniopharyngioma.

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

6. The use according to claim 5, characterized in that: The pharmaceutically acceptable excipients include at least one of a pharmaceutical solvent, a binder, a disintegrant, a flavoring agent, a colorant and a preservative.

7. A pharmaceutical preparation, characterized in that A pharmaceutical composition comprising at least one of nitazoxanide and a pharmaceutically acceptable salt thereof as claimed in any one of claims 4 to 6.

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

9. The pharmaceutical preparation according to claim 8, characterized in that The oral preparation includes at least one of tablets, capsules, granules, pills and solutions.

10. The pharmaceutical preparation according to claim 8, 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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