Pharmaceutical composition for the prevention or treatment of hearing loss, containing ammonium lactate as an active ingredient.

Abstract

The present invention relates to a pharmaceutical composition for the prevention or treatment of hearing loss containing ammonium lactate as an active ingredient. It has been confirmed that treating hair cells damaged by gentamicin with ammonium lactate increases the number of normal hair cells, and therefore, a pharmaceutical composition containing ammonium lactate as an active ingredient can be used to prevent or treat hearing loss, a side effect of using the antibiotic ammonium lactate.

Description

Technical Field

[0001] The present invention relates to a pharmaceutical composition for preventing or treating hearing loss, comprising ammonium lactate as an active ingredient.

Background Art

[0002] Gentamicin has been widely used as an excellent antibiotic for a long time and is a drug approved by the US Food and Drug Administration. It is an aminoglycoside antibiotic produced by Micromonospora purpurea and Micromonospora echinospora and is a mixture of gentamicin C1, C2, and C1a. Among Gram-positive bacteria, it is effective against staphylococci, and among Gram-negative bacteria, it is effective against Escherichia coli, Salmonella, Proteus, and Pseudomonas aeruginosa. Gentamicin is also used in the treatment of enterococcal endocarditis together with penicillin and ampicillin. It is administered by non-oral methods or widely used as a topical agent.

[0003] Recently, according to research publications, it is said that gentamicin can completely block the progression of Duchenne muscular dystrophy in which the drug effect is seen through the administration of antibiotics. However, it is known that typical side effects include permanent hearing loss and kidney damage.

[0004] Ototoxic hearing loss is a side effect caused by the use of ototoxic drugs, and aminoglycoside antibiotics and some anticancer drugs are known to induce ototoxicity. Aminoglycoside antibiotics exert their antibacterial effect by binding to bacterial 30s ribosome subunits and inhibiting protein synthesis. If such aminoglycoside antibiotics are continuously exposed to cochlear cells, outer hair cells and sensory hair cells of the organ of Corti will apoptosis. The mechanism of cell death is known to be due to reactive oxygen species (ROS) formed by the aminoglycoside antibiotic and Ca++ complex.

[0005] Most protective drugs for ototoxic hearing loss that have been developed and are currently undergoing clinical trials rely on blocking reactive oxygen species. Drugs that block reactive oxygen species have potent nuclei and have the efficacy of suppressing the generation of reactive oxygen species by forming complex compounds with antibiotics. However, this also reduces the effectiveness of the antibiotics, and they have a fundamental limitation in that their effect is minimal due to a nonspecific mechanism.

[0006] Therefore, there is a need to develop therapeutic agents that do not inhibit the effects of antibiotics and are effective in treating ototoxic hearing loss. [Overview of the Initiative] [Problems that the invention aims to solve]

[0007] The object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of hearing loss, comprising ammonium lactate as an active ingredient.

[0008] Another object of the present invention is to provide a health functional food composition for the prevention or improvement of hearing loss, comprising ammonium lactate as an active ingredient. [Means for solving the problem]

[0009] To achieve the aforementioned objective, the present invention provides a pharmaceutical composition for the prevention or treatment of hearing loss, comprising ammonium lactate as an active ingredient.

[0010] Furthermore, the present invention provides a health functional food composition for preventing or improving hearing loss, which contains ammonium lactate as an active ingredient. [Effects of the Invention]

[0011] This invention relates to a pharmaceutical composition for the prevention or treatment of hearing loss containing ammonium lactate as an active ingredient. It has been confirmed that treating hair cells damaged by gentamicin with ammonium lactate increases the number of normal hair cells, and therefore, a pharmaceutical composition containing ammonium lactate as an active ingredient can be used to prevent or treat hearing loss, a side effect of using the antibiotic ammonium lactate. [Brief explanation of the drawing]

[0012] [Figure 1] This is a diagram showing the molecular structure of ammonium lactate. [Figure 2] This is the result of checking the number of hair cells in zebrafish after administration of ammonium lactate. [Figure 3] This study confirmed the survival rate of hair cells in zebrafish after administration of ammonium lactate. [Modes for carrying out the invention]

[0013] The present invention will be described in more detail below.

[0014] The present invention provides a pharmaceutical composition for the prevention or treatment of hearing loss, comprising ammonium lactate as an active ingredient.

[0015] The aforementioned hearing loss is one or more of the following: ototoxic hearing loss, sudden hearing loss, noise-induced hearing loss, and age-related hearing loss.

[0016] The aforementioned ototoxic hearing loss is also hearing loss caused by anticancer drugs or aminoglycoside antibiotics.

[0017] The aforementioned anticancer drug is also cisplatin or carboplatin.

[0018] The aminoglycoside antibiotic may be selected from the group consisting of amikacin, arbekacin, kanamycin, gentamicin, neomycin, netilmicin, dibekacin, sisomycin, streptomycin, tobramycin, livodomycin, and paromomycin.

[0019] In other specific examples of the present invention, the pharmaceutical composition may further include one or more additives selected from the group consisting of carriers, excipients, disintegrants, sweeteners, coatings, leavening agents, lubricants, slicks, flavoring agents, antioxidants, buffers, bacteriostatic agents, diluents, dispersants, surfactants, binders, and lubricants, which are commonly used in the manufacture of pharmaceutical compositions. Specifically, the carrier, excipients, and diluents can be lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginic acid, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, amorphous cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. Solid formulations for oral administration include tablets, pills, powders, granules, and capsules. Such solid formulations can be prepared by mixing the composition with at least one excipient, such as starch, calcium carbonate, sucrose, or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc can also be used. Liquid formulations for oral administration include suspensions, oral solutions, emulsions, and syrups. In addition to commonly used simple diluents such as water and liquid paraffin, various excipients are included, such as humectants, sweeteners, fragrances, and preservatives. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, and suppositories. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases include witepsol, macrogol, tween 61, cocoa butter, lauric butter, and glycerogenous gelatin. According to one embodiment of the present invention, the pharmaceutical composition can be administered to a subject in a conventional manner via intravenous, intra-arterial, intraperitoneal, intramuscular, intrasternal, transdermal, nasal, inhalation, topical, rectal, oral, intraocular, or intradermal routes.The dosage of the active ingredient according to the present invention varies depending on the condition and weight of the subject, the type and severity of the disease, the drug form, the route of administration, and the duration, and is appropriately selected by those skilled in the art. The daily dose is 0.01 to 200 mg / kg, preferably 0.1 to 200 mg / kg, and more preferably 0.1 to 100 mg / kg. The drug can be administered once a day or in several divided doses, and this does not limit the scope of the present invention.

[0020] Furthermore, the present invention provides a health functional food composition for preventing or improving hearing loss, which contains ammonium lactate as an active ingredient.

[0021] The health functional food can contain various nutritional agents, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and fillers (such as cheese and chocolate), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, it can contain pulp for the production of natural fruit juices, synthetic fruit juices and vegetable beverages. Such components can be used independently or in combination. Also, the health functional food composition can be in any one form of meats, sausages, bread, chocolate, candies, snacks, confectioneries, pizza, ramen, gums, ice creams, soups, drinking water, tea, functional water, drink agents, alcohol and vitamin complexes. Further, the health functional food can further contain food additives, and the suitability as a "food additive" is determined by the standards and criteria for the relevant item according to the general rules and general test methods of the Food Additive Codex approved by the Food and Drug Safety Office, unless otherwise specified. Examples of the items listed in the "Food Additive Codex" include chemically synthesized products such as ketones, glycine, potassium citrate, nicotinic acid, cinnamic acid, natural additives such as indigo pigment, licorice extract, crystalline cellulose, gardenia pigment, guar gum, and mixed preparations such as sodium L-glutamate preparations, alkaline agents added to noodles, preservative preparations, tar pigment preparations, etc. At this time, the active ingredients added to the food in the process of manufacturing the health functional food can be appropriately adjusted in content as necessary, and preferably, they are added so as to be contained in 1 to 90 parts by weight per 100 parts by weight of the food.

[0022] Hereinafter, in order to assist in the understanding of the present invention, examples and the like will be given and described in detail. However, the following examples and the like illustrate the content of the present invention, and the scope of the present invention is not limited to the following examples and the like. The examples and the like of the present invention are provided to more fully explain the present invention to those skilled in the art.

[0023]

[0024] <Experimental Example 1> Rearing of Zebrafish Zebrafish larvae (wild type, Brn3c:EGFP, etc.) were cultured in the breeding room of this research institution. Each larva was cultured in embryo medium (15 mM NaCl, 0.5 mM KCl, 1 mM CaCl2, 1 mM MgSO4, 0.15 mM KH2PO4, 0.05 mM NH2PO4, and 0.7 mM NaHCO3).

[0025] <Experimental Example 2> Analysis of Hair Cells in Zebrafish After fertilization, gentamicin, an ototoxic inducer, was administered to zebrafish at around 5 days old to calculate the concentration (LC 50) and time of cisplatin that induces damage to about 50% of the hair cells in the lateral line of zebrafish. From the research results, when 50 μM of gentamicin was administered for 1 hour, about 50% of the hair cells were damaged, and this was selected. Thus, when ammonium lactate was simultaneously administered at 10 μM, 100 μM, 500 μM, and 1000 μM to 50 μM of gentamicin for 1 hour, its effect could be confirmed.

[0026] The positions of the hair cells in zebrafish are at four locations: the orbit (SO1 and SO2), the ear (O1), and the larynx (OC1). The number of hair cells was analyzed through a microscope (fluorescence microscope, confocal microscope, etc.). Candidate substances that can suppress the damage of hair cells by gentamicin were administered to zebrafish larvae at different concentrations, and their effects were compared and analyzed.

[0027] <Example 1> Verification of the Protective Effect of Ammonium Lactate on Hair Cells of Zebrafish To verify the protective effect of ammonium lactate on the hair cells of zebrafish, ammonium lactate and gentamicin were co-administered to zebrafish, and the survival rates of the control group and the hair cells were compared.

[0028] As a result, as shown in Figures 2 and 3, the number of hair cells in the untreated control group was 53. In the control group administered only 50 μM of gentamicin without ammonium lactate, there were 26 hair cells, and the survival rate decreased by 50%. Subsequently, it was confirmed that the survival rate of hair cells increased in a concentration-dependent manner in the groups administered 10 μM, 100 μM, 500 μM, and 1000 μM of ammonium lactate together with 50 μM of gentamicin. In particular, with 100 μM and 500 μM of ammonium lactate, there were 28 and 29 hair cells, respectively, and the survival rate increased by approximately 10%, while with 1000 μM of ammonium lactate, there were a total of 42 hair cells, and the survival rate increased by more than 60%.

[0029] Therefore, we were able to confirm that ammonium lactate has a protective effect on hair cells.

[0030] The above description of the present invention is illustrative, and those skilled in the art will understand that it can be easily modified into other specific forms without altering the technical idea or essential features of the invention. Therefore, it should be understood that the above-described embodiments are illustrative in all respects and not limiting.

[0031] The scope of this invention is defined by the claims described below, and all modified or altered forms derived from the meaning and scope of the claims and the concept of equivalents thereof should be interpreted as being included within the scope of this invention.

Claims

1. A pharmaceutical composition for the prevention or treatment of hearing loss, comprising ammonium lactate as an active ingredient.

2. The pharmaceutical composition according to claim 1, characterized in that the hearing loss is one or more of the group consisting of ototoxic hearing loss, sudden hearing loss, noise-induced hearing loss, and age-related hearing loss.

3. The pharmaceutical composition according to claim 2, characterized in that the ototoxic hearing loss is caused by an anticancer agent or an aminoglycoside antibiotic.

4. The pharmaceutical composition according to claim 3, characterized in that the anticancer agent is cisplatin or carboplatin.

5. The pharmaceutical composition according to claim 3, characterized in that the aminoglycoside antibiotic is one or more selected from the group consisting of amikacin, arbekacin, kanamycin, gentamicin, neomycin, netylmycin, dibekacin, shisomycin, streptomycin, tobramycin, ribodomycin, and paromomycin.

6. A health functional food composition containing ammonium lactate as an active ingredient for the prevention or improvement of hearing loss.

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