Medicament for treating meniere's disease and use thereof

Abstract

The present application relates to a kind of drug for treating Meniere's disease and its application, it includes active ingredient ebselen and acetazolamide, wherein the weight ratio of ebselen and acetazolamide is 8-12:1.The present application can effectively improve the treatment or relieve Meniere's disease by using acetazolamide and ebselen in a certain proportion, by synergism, especially, can simultaneously relieve the rotation caused by Meniere's disease, nystagmus and head left and right swing.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a drug for treating Meniere's disease and its application. Background Technology

[0002] Meniere's disease (MD), defined as a triad of episodic vertigo, hearing loss, and tinnitus, was first described by a French physician in 1861. Patients frequently report ear pressure or aural fullness, and most auditory and vestibular symptoms fluctuate in frequency and intensity. While the etiology of MD is unknown, it is associated with endolymphatic edema, the swelling of the endolymphatic compartments of the inner ear. Following an acute phase characterized by vertigo, a chronic phase develops, in which hearing loss and tinnitus become the most common features, although balance disturbances are frequently reported.

[0003] Because the etiology and pathogenesis of Meniere's disease are unclear, there is currently no cure. Treatment primarily involves medication and surgery to regulate autonomic nerve function, improve inner ear microcirculation, and relieve endolymphatic hydrops.

[0004] Drug treatment includes: (1) Vestibular nerve inhibitors are mostly used in the acute phase to weaken the activity of the vestibular nuclei and control vertigo. Commonly used ones include diazepam, diphenhydramine, and diphenidol. (2) Anticholinergic drugs such as anisodamine and scopolamine can relieve symptoms such as nausea and vomiting. (3) Vasodilators can change the metabolism of ischemic cells and selectively dilate blood vessels in the ischemic area to relieve local ischemia. Commonly used ones include flunarizine (Sibelium), betahistine, and ginkgo biloba tablets. (4) Diuretics can change the fluid balance of the inner ear, reduce endolymph, and control vertigo. Commonly used ones include hydrochlorothiazide and acetazolamide. (5) Glucocorticoids are based on the theory of immune response and can be used to treat vertigo with dexamethasone, prednisone, etc. (6) Vitamins can be used to treat vertigo caused by metabolic disorders or vitamin deficiency. Commonly used vitamins include vitamin B1, B12, and vitamin C.

[0005] Ebselen (EbSe) is a synthetically produced, lipid-soluble, selenium-containing organic small molecule compound with a wide range of physiological and pharmacological activities. As a typical representative of selenium-containing compounds, EbSe has been the subject of the most in-depth research. Early studies demonstrated that EbSe can maintain the physiological activity of various tissues by scavenging intracellular oxygen free radicals and inhibiting lipid peroxidation. Recent studies have found that the selenium-containing group of EbSe can affect the activity of protein cysteine ​​residues in its substrates, continuously expanding its potential applications and showing excellent potential for treatment in multiple human systems. Furthermore, the latest research confirms that EbSe also exhibits potent activity against multidrug-resistant bacterial infections.

[0006] Chinese patent application CN109475518A discloses a novel method and composition for treating MD and / or endolymphatic edema. The composition comprises ebuselenol and optionally one or more glutathione peroxidase (GPx) regulators or analogs and / or one or more prescription diuretic compounds.

[0007] For those skilled in the art, further research is needed on Meniere's disease to obtain more drugs that can effectively alleviate its symptoms. This invention is the result of research conducted to this purpose. Summary of the Invention

[0008] Based on the above background technology, the technical problem to be solved by the present invention is to provide a drug for treating Meniere's disease and its application. To achieve the objective of the present invention, the following technical solution is proposed:

[0009] One aspect of the present invention relates to a medicament for treating Meniere's disease, comprising the active ingredients ebuselenol and acetazolamide, wherein the weight ratio of ebuselenol to acetazolamide is 8 to 12:1; preferably 10:1.

[0010] In a preferred embodiment of the present invention, the drug may or may not contain other active ingredients.

[0011] In a preferred embodiment of the present invention, the drug is an oral preparation. The oral preparations of the present invention include, but are not limited to, tablets, capsules, and syrups. However, tablets are preferred.

[0012] In a preferred embodiment of the present invention, the excipients of the tablet include starch, croscarmellose sodium, and magnesium stearate.

[0013] Another aspect of the present invention relates to the application of the aforementioned drug for treating or alleviating Meniere's disease.

[0014] In a preferred embodiment of the invention, the drug is used to relieve rotational tremors, nystagmus, and / or head swaying caused by Meniere's disease.

[0015] Beneficial effects

[0016] This invention combines acetazolamide and ebuselenium in a certain ratio, which can effectively improve the treatment or relief of Meniere's disease through synergistic effects. In particular, it can simultaneously relieve rotation, nystagmus and head swaying caused by Meniere's disease. Detailed Implementation

[0017] To further understand the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0018] Unless otherwise specified, all reagents involved in the embodiments of this invention are commercially available products and can be purchased through commercial channels.

[0019] Example 1: Preparation of pharmaceutical formulation

[0020] Take 100g of ebuselenium and 10g of acetazolamide, add 80g of starch, 30g of croscarmellose sodium and 3g of magnesium stearate, and compress them into tablets containing 4mg ebuselenium / tablet.

[0021] Comparative Example 1:

[0022] Using the same formulation as in Example 1, except that 10g of acetazolamide was not added, positive control group 1 was prepared.

[0023] Comparative Example 2:

[0024] The same formulation as in Example 1 was used, except that 100g of ebuseline was completely replaced with 100g of acetazolamide, thus obtaining positive control group 2.

[0025] Comparative Example 3:

[0026] As a placebo, a placebo of the same tablet size as in Example 1 was prepared without the addition of the active ingredients ebuselenline and acetazolamide.

[0027] Example 2: Pharmacodynamic Experiment for Treating Meniere's Symptoms

[0028] Fifty experimental guinea pigs, weighing 240-300 grams each, half male and half female, were randomly divided into groups of 10. The guinea pigs were fasted for 12 hours prior to the experiment but allowed free access to water. Each guinea pig in the placebo group, positive control group, and experimental group was administered one tablet via gavage. The model group received no medication. The experiment was conducted 4 hours after administration.

[0029] 20 μL of chloroform was accurately injected deep into the external auditory canal using a microsyringe through a thin plastic tube. Clinical symptoms generally appeared about 10 minutes after administration: rapid rotation of the whole body towards the administration side, usually appearing 15-20 minutes after chloroform administration, followed by intermittent rotation, ceasing at approximately 60-80 minutes; this was the most severe symptom, and the number of rotations was recorded over 2 hours. Nystagmus and head swaying from side to side were secondary symptoms; the latter two indicators were counted at 20 and 40 minutes after chloroform administration, and the mean between groups was used as the index. The experimental results are shown in Table 1.

[0030] Table 1. Effects of drugs on Meniere's disease induced by chloroform in guinea pigs.

[0031]

[0032] The results showed that the placebo group had no substantial effect on symptom improvement. While positive control groups 1 and 2 could alleviate symptoms to some extent, the experimental group showed a significant reduction in vertigo and a marked improvement in nystagmus and head swaying. This demonstrates that the drug of this invention can simultaneously relieve multiple symptoms and has a good therapeutic effect on the Meniere's disease pathological model.

[0033] The preferred embodiments of the present invention have been described above, but are not intended to limit the invention. Those skilled in the art can make modifications and variations to the embodiments disclosed herein without departing from the scope and spirit of the invention.

Claims

1. A medicament for treating Meniere's disease, comprising the active ingredients ebuselenol and acetazolamide, wherein the weight ratio of ebuselenol to acetazolamide is 8-12:1; the medicament does not contain other active ingredients; the medicament is an oral preparation.

2. The drug according to claim 1, wherein the oral preparation is a tablet, capsule, or syrup.

3. The medicament according to claim 1, wherein the oral formulation is a tablet.

4. The medicament according to claim 3, wherein the excipients of the tablet include starch, croscarmellose sodium, and magnesium stearate.

5. The use of the medicament according to any one of claims 1-4, wherein the medicament is used to prepare a medicament for treating or alleviating Meniere's disease.

6. The use of the medicament according to any one of claims 1-4, wherein the medicament is used to prepare a medicament for relieving rotation, nystagmus and / or head swaying caused by Meniere's disease.

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