KR20190050074A - Composition for protecting kidney containing chalcone derivatives - Google Patents

Abstract

The present invention relates to a composition for protecting a kidney or a composition for alleviating kidney diseases which contains a chalcone derivative. When the compound according to the present invention is used, the kidney can be protected from nephrotoxicity due to drugs and the like. Therefore, by utilizing the present specification, it is possible to make a great contribution to fields of patient treatment and welfare.

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for protecting kidneys containing chalcone derivatives,

The present invention relates to a composition for protecting kidneys containing a chalcone derivative or a composition for improving a kidney disease.

Kidney is an important excretory organ that excretes urine in the body. Several medicines and environmental pollutants are toxic to the kidneys. Typical drugs causing renal toxicity include non-steroidal anti-inflammatory analgesics such as phenacetin, aspirin, and indomethacin; Anticancer agents such as puromycin, daunomycin, cyclophosphamide, penicillamine, adriamycin and cisplatin, immunosuppressants, amikacin, gentamycin, kanamycin, neomycin, sisomycin, streptomycin, tobramycin Aminoglycoside antibiotics; Cephalosporin antibiotics; Carbapenem antibiotics such as imipenem and melopenem; Heavy metals such as cadmium, lead, mercury, and chromium; And inorganic and organic heavy metal compounds, compounds such as chloroform, D-serine, sulfonamide, 2-bromoethylene and hydrobromide, or fungal toxins such as okara-toxin and citrinin. Renal diseases caused by nephrotoxicity to these drugs include nephritis, pyelonephritis, nephrotic syndrome, renal cancer, acute pyelonephritis, chronic pyelonephritis, renal tuberculosis, urinary tract infection, urinary stone, ureter stones, acute renal failure, chronic renal failure, Diabetic nephropathy, chronic glomerulonephritis, acute progressive nephritis, nephrotic syndrome, pancreatic glomerulosclerosis, membranous sinusitis, or membranous proliferative glomerulonephritis.

Therefore, studies are being conducted to prevent or treat the above diseases. However, commercialization of a kidney protective substance that can effectively prevent or treat renal toxicity caused by a renal toxicity-inducing substance has not been satisfactory compared to the demand.

Korean Patent Publication No. 10-2014-0037633 (Apr. 31, 2014)

It is an object of the present invention to provide a material for renal protection and improvement of kidney disease which is insufficient in comparison with demand, to prevent drug side effects and the like and to achieve the therapeutic purpose of related patients early.

In order to solve the above problems, the present invention provides a chalcone derivative having the structure of the following formula (16), an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof.

[Chemical Formula 16]

According to one embodiment, R ₁ is H, OH or OC _n H _{2n +1} (n is an integer selected from 1 to 5) and R ₂ is H, OH or C _n H _{2n +1} (n is an integer selected from 1 to 5), R ₃ is H, OC _n H _{2n +1} (n is an integer selected from 1 to 5) or a halogen group, R ₄ is H, OH Or C _n H _{2n + 1} , wherein n is an integer selected from 1 to 5, and R ₅ is H, OH or C _n H _{2n +1} (n is an integer selected from 1 to 5) R ₆ is H or a halogen group, R ₇ is H, a methyl group or an ethyl group, R ₈ is H, OC _n H _{2n +1} (n is an integer selected from 1 to 5) ₉ may be H, OH or C _n H _{2n + 1} , where n is an integer selected from 1 to 5.

The present invention also provides a composition for the prevention of renal diseases, composition for preventing or treating renal disease, or a composition for preventing or treating renal disease, which comprises the chalcone derivative, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof as an active ingredient.

The use of the compound according to the present invention can protect the kidney from nephrotoxicity and can effectively improve the kidney disease associated with the drug, so that the present invention can be utilized to make a great contribution in the field of patient treatment and welfare There will be.

FIGS. 1A to 1C are graphs showing the new preservation efficacy of the chalcone derivatives 1 to 15 according to one aspect of the present invention.
FIG. 2 is an image analysis of the new preservation efficacy of Chalcone Derivative 3 (Compound 3) according to one aspect of the present invention.

As used herein, the term "platinum-based anticancer agent" refers to an anticancer agent containing a platinum Pt atom, and includes a platinum derivative series and a platinum complex series. Types of platinum-based anticancer drugs include cisplatin, oxaliplatin, and carboplatin.

As used herein, " alkyl " means a monovalent saturated aliphatic hydrocarbon chain. The hydrocarbon chain can be linear or branched. In one aspect of the present invention "alkyl" are one to six carbon atoms ( "C ₁ to C ₅ alkyl") can have, and from 1 to 5 carbon atoms ( "C ₁ to C ₅ alkyl." In one aspect ), From 1 to 4 carbon atoms ("C ₁ to C ₄ alkyl"), and in yet another aspect from 1 to 3 carbon atoms ("C ₁ to C ₃ alkyl"). Specifically, "alkyl" includes but is not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, tert-butyl or t-amyl.

As used herein, the term " isomers " refers in particular to optical isomers (for example, essentially pure enantiomers, essentially pure diastereomers or mixtures thereof) as well as morphological isomers (i. e., isomers differing only in the angle of one or more chemical bonds), position isomers (especially tautomers) or geometric isomers (e.g., cis-trans isomers) do.

As used herein, " essentially pure ", when used in reference to an enantiomer or partial isomer, means that at least about 90%, preferably at least about 95%, of a specific compound, such as an enantiomer or partial isomer, , More preferably at least about 97% or at least about 98%, even more preferably at least about 99%, even more preferably at least about 99.5% (w / w).

As used herein, the term " pharmaceutically acceptable " refers to the approval of a government or equivalent regulatory agency that can be used on animals, and more specifically on humans, by avoiding significant toxic effects when used in conventional medicinal dosage Received, approved, or listed in pharmacopoeia or other general pharmacopoeia.

As used herein, the term " pharmaceutically acceptable salt " refers to a concentration that is relatively non-toxic and harmless to the patient and has a beneficial effect, and that side effects due to the salt do not detract from the beneficial effects of the compound represented by formula Means any and all organic or inorganic addition salts of such compounds having the desired pharmacological activity of the parent compound.

The salt may be (1) formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like; (3-hydroxybenzoyl) benzoic acid, or an acetic acid, propionic acid, hexanoic acid, cyclopentenepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, Benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4- chlorobenzenesulfonic acid, 2- 4-methylbicyclo [2,2,2] -oct-2-en-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert Acid addition salts formed with organic acids such as butylacetic acid, laurylsulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid; Or (2) salts formed when the acidic proton present in the parent compound is substituted.

The acid addition salt is prepared by a conventional method, for example, by dissolving the compound in an excess amount of an acid aqueous solution, and precipitating the salt using a water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. The same molar amount of the compound and the acid or alcohol (e.g., glycol monomethyl ether) in water may be heated and then the mixture may be evaporated to dryness, or the precipitated salt may be subjected to suction filtration.

As the free acid, organic acids and inorganic acids can be used. As the inorganic acids, hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid and the like can be used. Examples of the organic acids include methanesulfonic acid, p- toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, citric acid, lactic acid, glycollic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid and the like can be used , But are not limited to these.

In addition, bases can be used to make pharmaceutically acceptable metal salts. The alkali metal salt or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess amount of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the non-soluble salt salt, and evaporating and drying the filtrate. At this time, it is pharmaceutically acceptable to produce sodium, potassium, or calcium salt, but not limited thereto. The corresponding silver salt can also be obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (e.g., silver nitrate).

As used herein, " hydrate " means a compound to which water is bound, and is a broad concept that includes an inclusion compound having no chemical bonding force between water and the compound.

As used herein, " solvate " means a higher order compound formed between a molecule or ion of a solute and a molecule or ion of a solvent.

In one aspect, the present invention can be a chalcone derivative having the structure of the following formula (16), an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof.

[Chemical Formula 16]

Wherein R ₁ is H, OH or OC _n H _{2n +1} (n is an integer selected from 1 to 5) and R ₂ is H, OH or C _n H _{2n +1} is an integer) is selected from, R ₃ is _{H, OC n H 2n +1 (} n is an integer selected from 1 to 5) or a halogen group, R ₄ is H, OH or C _n H _{2n + 1} , wherein n is an integer selected from 1 to 5, and R ₅ is H, OH or C _n H _{2n +1} (n is an integer selected from 1 to 5), R ₆ is H, or ( _Wherein n is an integer selected from 1 to 5) or a halogen group, and R ₉ is H, OH or a halogen group, R ₇ is H, a methyl group or an ethyl group, R ₈ is H, OC _n H _{2n +1} C _n H _{2n +1} (n is an integer selected from 1 to 5).

In one embodiment, when at least one of R ₃ , R _6, and R ₈ is a halogen group, the halogen group may be F, Cl, or Br.

In another embodiment, the chalcone derivative is (E) -3- (2-bromo-4,5-dimethoxyphenyl) -1-phenylprop-2-en-1-one; (E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (3,4-dimethoxyphenyl) prop-2-en-1-one; E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2-hydroxy-5-methylphenyl) prop-2-en-1-one; (E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2,6-dihydroxyphenyl) prop-2-en-1-one; (E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2-hydroxy-4,6-dimethoxyphenyl) propo-2-en-1-one; (E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2-hydroxyphenyl) propo-2-en-1-one; (E) -3- (4-chlorophenyl) -1-phenylprop-2-en-1-one; (E) -3- (4-chlorophenyl) -1- (3,4-dimethoxyphenyl) propo-2-en-1-one; (E) -3- (4-chlorophenyl) -1- (2-hydroxy-5-methylphenyl) propo-2-en-1-one; (E) -1- (4-bromophenyl) -3- (4-chlorophenyl) prop-2-en-1-one; (E) -3- (4-chlorophenyl) -1- (2,6-dihydroxyphenyl) propo-2-en-1-one; (E) -3- (4-chlorophenyl) -1- (2-hydroxy-4,6-dimethoxyphenyl) propo-2-en-1-one; (E) -3- (4-chlorophenyl) -1- (2-hydroxyphenyl) propo-2-en-1-one; (E) -1,3-bis (4-chlorophenyl) prop-2-en-1-one; And (E) -3- (4-chlorophenyl) -1- (4-fluorophenyl) propo-2-en-1-one.

In one aspect, the present invention can be a composition for protecting elongation comprising chalcone derivative having the structure of the following formula (16), an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof as an active ingredient.

[Chemical Formula 16]

Wherein R ₁ is H, OH or OC _n H _{2n +1} (n is an integer selected from 1 to 5) and R ₂ is H, OH or C _n H _{2n +1} is an integer) is selected from, R ₃ is _{H, OC n H 2n +1 (} n is an integer selected from 1 to 5) or a halogen group, R ₄ is H, OH or C _n H _{2n + 1} wherein n is an integer selected from 1 to 5, and R ₅ is H, OH or C _n H _{2n + 1} (n is an integer selected from 1 to 5), R ₆ is H, or ( _Wherein n is an integer selected from 1 to 5) or a halogen group, and R ₉ is H, OH or a halogen group, R ₇ is H, a methyl group or an ethyl group, R ₈ is H, OC _n H _{2n +1} C _n H _{2n +1} (n is an integer selected from 1 to 5).

In another aspect, the present invention may be a composition for improving kidney disease comprising chalcone derivative having the structure of Chemical Formula 16, an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof as an active ingredient. In one embodiment, the improvement includes treatment, prevention, symptom relief, and the like.

In one aspect, when at least one of R ₃ , R _6, and R ₈ is a halogen group, the halogen group may be F, Cl, or Br.

In another aspect, the pharmaceutically acceptable salts of the chalcone derivatives include salts of acidic or basic groups that may be present in the chalcone derivatives, unless otherwise indicated. For example, pharmaceutically acceptable salts may include sodium salts, calcium salts and potassium salts of hydroxy groups and the like. Other pharmaceutically acceptable salts of amino groups include hydrobromides, sulfates, hydrogen sulfates, phosphates, (Mesylate), and p-toluenesulfonate (tosylate) salts, which are known in the art, such as hydrogen phosphate, dihydrogen phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate Can be prepared via known methods for preparing salts.

In another aspect, the chalcone derivative is (E) -3- (2-bromo-4,5-dimethoxyphenyl) -1-phenylprop-2-en-1-one; (E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (3,4-dimethoxyphenyl) prop-2-en-1-one; (E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2-hydroxy-5-methylphenyl) prop-2-en-1-one; (E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2,6-dihydroxyphenyl) prop-2-en-1-one; (E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2-hydroxy-4,6-dimethoxyphenyl) propo-2-en-1-one; (E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2-hydroxyphenyl) propo-2-en-1-one; (E) -3- (4-chlorophenyl) -1-phenylprop-2-en-1-one; (E) -3- (4-chlorophenyl) -1- (3,4-dimethoxyphenyl) propo-2-en-1-one; (E) -3- (4-chlorophenyl) -1- (2-hydroxy-5-methylphenyl) propo-2-en-1-one; (E) -1- (4-bromophenyl) -3- (4-chlorophenyl) prop-2-en-1-one; (E) -3- (4-chlorophenyl) -1- (2,6-dihydroxyphenyl) propo-2-en-1-one; (E) -3- (4-chlorophenyl) -1- (2-hydroxy-4,6-dimethoxyphenyl) propo-2-en-1-one; (E) -3- (4-chlorophenyl) -1- (2-hydroxyphenyl) propo-2-en-1-one; (E) -1,3-bis (4-chlorophenyl) prop-2-en-1-one; And (E) -3- (4-chlorophenyl) -1- (4-fluorophenyl) propo-2-en-1-one.

In another aspect, the concentration of the chalcone derivative, its isomer, its pharmaceutically acceptable salt, its hydrate or solvate thereof in the composition may be from 0.001 μM to 5M. In one embodiment, the concentration is at least about 0.001 M, at least 0.01 M, at least 0.1 M, at least 1 M, at least 10 M, at least 25 M, at least 50 M, at least 100 M, at least 125 M, at least 150 M, at least 200 M, at least 250 M, at least 300 M, 500 μM or more, 1 mM or more, 50 mM or more, 100 mM or more, 500 mM or more, 1 M or more, or 5 M or more. In other embodiments, the concentration may be less than or equal to 5M, less than or equal to 1M, less than or equal to 500mM, less than or equal to 100mM, less than or equal to 50mM, less than or equal to 1mM, less than or equal to 500MM, less than or equal to 400MM, less than or equal to 300MM, less than or equal to 250MM, less than or equal to 200MM, less than or equal to 150MM, Less than or equal to 25 μM, less than or equal to 10 μM, less than or equal to 1 μM, less than or equal to 0.1 μM, less than or equal to 0.01 μM, or less than or equal to 0.005 μM.

In another aspect, the dosage of the chalcone derivative, its isomer, its pharmaceutically acceptable salt, its hydrate or its solvate may be from 0.0001 mg / kg / day to 80 mg / kg / day. In one embodiment, the dose is at least 0.0001 mg / kg / day, at least 0.001 mg / kg / day, at least 0.01 mg / kg / day, at least 0.1 mg / kg / day, more than 5 mg / kg / day, greater than 10 mg / kg / day, greater than 20 mg / kg / day, greater than 30 mg / kg / day, greater than 50 mg / kg / day, greater than 60 mg / / kg / day. In another embodiment, the dosage is less than or equal to 80 mg / kg / day, less than or equal to 70 mg / kg / day, less than or equal to 60 mg / kg / day, less than or equal to 50 mg / kg / day, less than or equal to 40 mg / Kg / day, up to 10 mg / kg / day, up to 5 mg / kg / day, up to 3 mg / kg / day, up to 1 mg / kg / day, up to 0.5 mg / Day or less, 0.01 mg / kg / day or less, 0.005 mg / kg / day or less, 0.001 mg / kg / day or less, or 0.0005 mg / kg / day or less.

In one embodiment, the composition may be a pharmaceutical composition or a food composition.

In another embodiment, the kidney protection may be kidney protection from nephrotoxicity by the drug. In one aspect, the nephrotoxicity may be nephrotoxicity due to oxidative stress.

In another embodiment, the kidney disease may be a kidney disease due to adverse drug reactions.

In one aspect of the invention, the medicament is a non-steroidal analgesic anti-inflammatory agent such as phenacetin, aspirin, indomethacin and the like; Aminoglycoside antibiotics such as puromycin, daunomycin, cyclophosphamide, penicillamine, adriamycin, amikacin, gentamicin, kanamycin, neomycin, sisomycin, streptomycin and tobramycin; Cephalosporin antibiotics; Carbapenem antibiotics such as imipenem and melopenem; Immunosuppressants; Heavy metals such as cadmium, lead, mercury, and chromium; And inorganic and organic heavy metal compounds, chloroform, D-serine, sulfonamide, 2-bromoethylene, and hydrobromide; Or a fungal toxin such as okarotoxin, citrinin.

In one embodiment, the drug may be an anti-cancer agent.

In one aspect, the anticancer agent may be a platinum-based anticancer agent. The platinum-based anticancer agent may be at least one selected from the group consisting of cisplatin, oxaliplatin, and carboplatin, for example.

In another aspect, the renal disease is selected from the group consisting of nephritis, pyelitis, nephrotic syndrome, renal cancer, acute pyelonephritis, chronic pyelonephritis, renal tuberculosis, urinary tract infection, urinary stone, ureter stones, acute renal failure, chronic renal failure, Nephritis, nephritis, acute progressive nephritis, nephrotic syndrome, pancreatic glomerulosclerosis, membranous sinusitis, and membranoproliferative glomerulonephritis. In one embodiment, the disease may be a disease as a side effect of a drug or an anti-cancer agent.

In one aspect of the present invention, nephrotoxicity may be characterized by neurotoxicity due to a drug. Specifically, in one aspect of the present invention, nephrotoxicity may be nephrotoxicity induced by an anticancer agent, i.e., as an anticancer agent adverse effect.

The pharmaceutical compositions according to the present disclosure may be of various oral or parenteral formulations. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid form preparations for oral administration include tablets, pills, powders, granules, soft or hard capsules, etc. These solid preparations may contain one or more excipients such as starch, calcium carbonate, sucrose, Or lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.

The pharmaceutical dosage forms of the compositions of the present invention may be used in the form of their pharmaceutically acceptable salts, and may be used alone or in combination with other pharmaceutically active compounds as well as in suitable aggregates. The salt is not particularly limited as long as it is pharmaceutically acceptable so long as it is pharmaceutically acceptable and includes, for example, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, hydrobromic acid, formic acid acetic acid, tartaric acid, lactic acid, citric acid, fumaric acid, , Benzenesulfonic acid, toluenesulfonic acid, and naphthalenesulfonic acid.

The composition of the present invention may be administered parenterally or orally, and may be administered once to several times a day, as desired. The dosage for a particular patient may vary depending on the patient's body weight, age, sex, health condition, diet, time of administration, administration method, excretion rate, severity of disease, and the like.

The pharmaceutical composition according to the present invention can be administered orally or parenterally in the form of powders, granules, tablets, soft or hard capsules, oral preparations such as suspensions, emulsions, syrups and aerosols, external preparations such as ointments and creams, Sterile injection solutions, and the like, and may be formulated in any form suitable for pharmaceutical preparations.

The composition according to the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like by various routes such as parenteral, oral, and the like, and any manner of administration can be expected. For example, Rectal administration, intravenous, intramuscular, subcutaneous injection, and the like.

Meanwhile, since the composition according to the present invention has no serious toxicity and side effects, it can be safely used for prolonged use for preventive purposes.

The formulation of the food composition according to the present specification is not particularly limited, but may be formulated into, for example, tablets, granules, powders, liquid preparations such as a drink, caramels, gels, bars and the like. The food composition of each formulation can be mixed with the ingredients commonly used in the field in addition to the chalcone derivative without difficulty by those skilled in the art depending on the purpose of formulation or use, and synergistic effect can be obtained when they are applied simultaneously with other ingredients.

In the food composition according to the present invention, the determination of the dose of the chalcone derivative is within the level of those skilled in the art, and may vary depending on various factors such as the age, health condition, and complication of the subject to be administered.

The food composition according to the present invention may be used as a food or beverage such as various foods such as chewing gum, caramel product, candy, ice cream, confectionery, beverage such as soft drink, mineral water, alcoholic beverage, healthful food including vitamins and minerals .

The beverage containing the chalcone derivative according to one aspect of the present invention is not particularly limited to the other ingredients other than the chalcone derivative as an essential ingredient in the indicated ratios and may contain various flavors or natural carbohydrates such as ordinary beverages, As shown in FIG.

In addition to the above, the health food composition of the present invention may further contain various additives such as various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate etc.), pectic acid and its salts, A salt thereof, an organic acid, a protective colloid thickener, a pH adjusting agent, a stabilizer, a preservative, a glycerin, an alcohol, a carbonating agent used in a carbonated drink, and the like. In addition, the functional food compositions of the present invention may comprise natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally included in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

Hereinafter, the method of the present invention will be specifically described by way of Examples, Experimental Examples, Formulation Examples and the like. However, the following examples are intended to illustrate only one aspect of the present invention, and the scope of the present invention is not limited to these examples.

Example 1 Synthesis of (E) -3- (2-bromo-4,5-dimethoxyphenyl) -1-phenylprop-2-en-

The general process for preparing the chalcone derivative according to one aspect of the present invention is shown in the following figure.

That is, Compound 1 (1 in the above figure) and Compound 2 (2 in the above figure) were dissolved in ethyl alcohol and reacted by treating with 8 N sodium hydroxide solution. Compound 3 (3 in the figure) was obtained by column chromatography I will. The equipment to be used at this time may suffice to use those conventionally used in the art.

The obtained compound 3 is treated with 1N HCl / MeOH and refluxed, and then purified by column chromatography to obtain compound 4 (4 in the figure).

(E) -3 (2-bromo-4,5-dimethoxyphenyl) -1-phenylprop-2-en-1-one represented by the following formula - (2-bromo-4,5-dimethoxyphenyl) -1-phenylprop-2-en-1-one)

[Chemical Formula 1]

Specifically, acetophenone (40 mg, 0.33 mmol) was dissolved in ethyl alcohol (4 ml), followed by addition of 2-bromo-4,5-dimethoxyphenylaldehyde (80.52 mg, 0.33 mmol) followed by addition of 8N sodium hydroxide ml) was treated and stirred at room temperature for 24 hours. After the reaction was completed, the pH was adjusted to 7.0, and the mixture was extracted with ethyl acetate. The extract was purified by using a silica gel column and ethyl acetate: hexane = 1: 5 to obtain Compound 1 (42 mg, 37.8%).

Detailed NMR data are shown below.

¹ H-NMR (CDCl 3): 8.07 ppm (d, J = 15.6 Hz, 1H), 8.04 ppm-7.98 ppm (m, 2H), 7.63 ppm-7.55 ppm 2H), 7.29 ppm (d, J = 15.2 Hz, 1H), 7.20 (s, 1H), 7.09 (s, 1H), 3.95 ppm (s, 3H), 3.92 ppm (s, 3H).

ESI-MS: m / z calcd for C 17 H 16 BrO 3 [M + H] = 347.02 found 347.0.

[Example 2] (E) -3- (2-Bromo-4,5-dimethoxyphenyl) -1- (3,4-dimethoxyphenyl) Synthesis of 2-bromo-4,5-dimethoxyphenyl) -1- (3,4-dimethoxyphenyl) prop-2-en-

4-dimethoxyacetophenone (30 mg, 0.167 mmol) was dissolved in ethyl alcohol (4 ml), and then 2-bromo-4,5-dimethoxyphenylaldehyde (40.7 mg, 0.167 mmol) A solution of sodium hydroxide (0.5 ml) was treated and stirred at room temperature for 24 hours. Thereafter, the pH was adjusted to 7.0, extracted with ethyl acetate, and then purified on a silica gel column and ethyl acetate: hexane = 1: 5 to obtain Compound 2 (38.2 mg, 56.3%) represented by the following formula (2).

(2)

Detailed NMR data are shown below.

¹ H-NMR (CDCl ₃ ): 8.05 ppm (d, J = 15.6 Hz, 1H), 7.66 ppm (dd, J = 8.4 Hz, 2 Hz, 1H) (S, 3H), 3.95 ppm (s, 3H), 3.95 ppm (s, 1H) ), 3.92 ppm (s, 3H).

ESI-MS: m / z calcd for C 19 H 20 BrO 5 [M + H] = 407.04 found 407.0.

[Example 3] (E) -3- (2-Bromo-4,5-dimethoxyphenyl) -1- (2-hydroxy-5-methylphenyl) Synthesis of 3-bromo-4,5-dimethoxyphenyl-1- (2-hydroxy-5-methylphenyl) prop-2-en-

After dissolving 2-hydroxy-5-methylacetophenone (30 mg, 0.2 mmol) in ethyl alcohol (4 ml), 2-bromo-4,5-dimethoxyphenylaldehyde (48.8 mg, 0.2 mmol) 8N sodium hydroxide (0.5 ml) was treated and stirred at room temperature for 24 hours. Thereafter, the pH was adjusted to 7.0, and the mixture was extracted with ethyl acetate. The extract was purified by a silica gel column and ethyl acetate: hexane = 1: 5 to obtain 42.1 mg (56.0%) of a compound 3 represented by the following formula 3.

(3)

Detailed NMR data are shown below.

¹ H-NMR (CDCl ₃ ): 12.60 ppm (s, 1H), 12.6 ppm (s, 1H), 8.20 ppm (d, J = 15.2 Hz, CH = 1H), 7.41 ppm (d, J = 15.2 Hz, 1H), 7.32 ppm (dd, J = 8.4 ppm, ), 6.94 ppm (d, J = 8.4 Hz, 1H), 3.98 ppm (s, 3H), 3.93 ppm (s, 3H). ESI-MS: m / z calcd for C 18 H 18 BrO 4 [M + H] = 377.04 found 377.0.

Example 4 Synthesis of (E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2,6-dihydroxyphenyl) Synthesis of 4- (2-bromo-4,5-dimethoxyphenyl) -1- (2,6-dihydroxyphenyl) prop-2-en-

After dissolving 1- (2,6-bis (methoxymethoxy) acetophenone (48 mg, 0.2 mmol) in ethyl alcohol (4 ml), 2-bromo-4,5-dimethoxyphenylaldehyde (48.8, 0.2 After adjusting the pH to 7.0, the mixture was extracted with ethyl acetate and purified by silica gel column and ethyl acetate: hexane = 1: 5. The residue was dissolved in a 1N hydrochloric acid solution (1.5 ml) / methanol (5 ml) and refluxed for 1 hour. The residue was purified by a silica gel column using ethyl acetate: hexane = 1: 2, 4 (42.1 mg, 55.7%).

[Chemical Formula 4]

Detailed NMR data are shown below.

_{^{1 H-NMR (CDCl 3)}} : 9.56 ppm (s, 2H), 8.16 ppm (d, J = 15.6 Hz, 1H), 7.85 ppm (d, J = 15.2 Hz, 1H), 7.25 ppm (m, 1H) , 7.19 ppm (s, 1H), 7.09 ppm (s, 1H), 6.44 ppm (d, J = 8 Hz, 2H), 3.92 ppm (s, 3H), 3.91 ppm (s, 3H). ESI-MS: m / z calcd for C 17 H 16 BrO 5 [M + H] = 379.04 found 379.0.

[Example 5] (E) -3- (2-Bromo-4,5-dimethoxyphenyl) -1- (2-hydroxy-4,6-dimethoxyphenyl) prop- Synthesis of (E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2-hydroxy-4,6-dimethoxyphenyl) prop-2-en-

2-Bromo-4,5-dimethoxyphenylaldehyde (48.8 mg, 0.2 mmol) was dissolved in ethyl alcohol (4 ml) And the mixture was treated with 8N sodium hydroxide (0.5 ml) and stirred at room temperature for 24 hours. The pH was adjusted to 7.0, extracted with ethyl acetate, and purified using a silica gel column and ethyl acetate: hexane = 1: 5 to obtain 48.6 mg (57.6%) of a compound 5 represented by the following formula 5.

[Chemical Formula 5]

Detailed NMR data are shown below.

¹ H-NMR (CDCl ₃ ): 14.28 ppm (s, 1H, phenolic OH), 8.07 ppm (d, J = 15.6 Hz, J = 2.4 Hz, 1H), 3.93 ppm (s, 1H), 7.17 ppm (s, 3H), 3.92 ppm (s, 3H), 3.90 (s, 3H), 3.84 ppm (s, 3H). ESI-MS: m / z calcd for C 19 H 20 BrO 6 [M + H] = 423.04 found 423.0.

Example 6 Synthesis of (E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2-hydroxyphenyl) prop- Synthesis of 3- (2-bromo-4,5-dimethoxyphenyl) -1- (2-hydroxyphenyl) prop-2-en-

2-Bromo-4,5-dimethoxyphenylaldehyde (48.8 mg, 0.2 mmol) was added to the solution, and then 8N sodium hydroxide ( 0.5 ml) was treated and stirred at room temperature for 24 hours. The pH was adjusted to 7.0 and then extracted with ethyl acetate. The residue was purified using a silica gel column and ethyl acetate: hexane = 1: 5 to obtain Compound 6 (36.9 mg, 51.0%) represented by the following Formula 6.

[Chemical Formula 6]

Detailed NMR data are shown below.

_{^{1 H-NMR (CDCl 3)}} : 12.8 ppm (s, 1H), 8.24 ppm (d, J = 15.2 Hz, 1H), 7.93 ppm (d, J = 8.0 Hz, 1H), 7.52 ppm (m, 1H) , 7.99 (d, J = 15.2 Hz, 1H), 7.28 ppm (s, 1H), 7.10-7.00 ppm (m 2H), 6.97 ppm , 3.93 ppm (s, 3H). ESI-MS: m / z calcd for C 17 H 16 BrO 4 [M + H] = 363.02 found 263.0.

[Example 7] (E) -3- (4-chlorophenyl) -1-phenylprop-2-ene -1-one) (7) Synthesis of

4-Chlorophenyl aldehyde (28 mg, 0.2 mmol) was added to the solution, and then 8N sodium hydroxide (0.5 ml) was added thereto. The mixture was stirred at room temperature for 24 hours, Respectively. The pH of the mixture was adjusted to 7.0, extracted with ethyl acetate (100 ml), and then purified using a silica gel column and ethyl acetate: hexane = 1: 5 to obtain 22.1 mg (49.3% .

(7)

Detailed NMR data are shown below.

¹ H-NMR (CDCl ₃ ): 8.40 ppm-7.99 ppm (m, 2H), 7.76 ppm (d, J = 15.6 Hz, -7.46 ppm (m, 3H), 7.44 ppm- 7.37 ppm (m, 2H). ESI-MS: m / z calcd for C 15 H 12 ClO [M + H] = 243.06 found 243.1.

[Example 8] (E) -3- (4-chlorophenyl) -1- (3,4-dimethoxyphenyl) ) -1- (3,4-dimethoxyphenyl) prop-2-en-1-one) (8)

4-Chlorophenyl aldehyde (28 mg, 0.22 mmol) was added to a solution of 3,4-dihydroxyacetophenone (36 mg, 0.22 mmol) in ethyl alcohol (4 ml), followed by the addition of 8N sodium hydroxide And the mixture was stirred at room temperature for 24 hours. The pH was adjusted to 7.0 and then extracted with ethyl acetate. The residue was purified using a silica gel column and ethyl acetate: hexane = 1: 5 to obtain Compound 8 (38.2 mg, 63.24%) represented by the following formula 8.

[Chemical Formula 8]

Detailed NMR data are shown below.

_{^{1 H-NMR (CDCl 3)}} : 7.74 ppm (d, J = 15.6 Hz, 1H), 7.67 ppm (dd, J = 8.4 Hz, 2.0 Hz, 1H), 7.62 ppm (d, J = 1.6 Hz, 1H) , 7.59 ppm-7.48 ppm (m, 3H), 7.38 ppm (d, J = 8.4 Hz, 2H), 6.62 ppm (d, J = 8.4 Hz, 1H), 3.97 ppm (s, 6H). ESI-MS: m / z calcd for C 17 H 15 ClO 3 [M + H] = 303.08 found 303.1.

Example 9 Synthesis of (E) -3- (4- (4-fluorophenyl) -5-methylphenyl) chlorophenyl) -1- (2-hydroxy-5-methylphenyl) prop-2-en-1-one)

2-Hydroxy-5-methylacetophenone (38.8 mg, 0.2 mmol) was dissolved in ethyl alcohol (4 ml), followed by addition of 4-chlorophenylaldehyde (29.4 mg, 0.2 mmol) followed by the addition of 8N sodium hydroxide And the mixture was stirred at room temperature for 24 hours. The pH was adjusted to 7.0, extracted with ethyl acetate, and purified using a silica gel column and ethyl acetate: hexane = 1: 5 to obtain Compound 9 (31.7 mg, 58.2%) represented by the following formula 9.

[Chemical Formula 9]

Detailed NMR data are shown below.

¹ H-NMR (CDCl ₃ ): 12.56 ppm (s, 1 H), 7.86 ppm (d, J = 15.6 Hz, ), 7.45 ppm-7.40 ppm (m, 2H), 7.33 ppm (dd, J = 8.4 Hz, 2.4 Hz, 1H), 6.94 ppm (d, J = 8.4 Hz, 1H), 2.36 ppm (s, 3H). ESI-MS: m / z calcd for C 16 H 14 ClO 2 [M + H] = 273.07 found 273.1.

Example 10 Synthesis of (E) -1- (4-bromophenyl) -3- (4-chlorophenyl) Synthesis of 3- (4-chlorophenyl) prop-2-en-1-one) (10)

4-Bromoacetophenone (39.6 mg, 0.2 mmol) was dissolved in ethyl alcohol (4 ml), followed by addition of 4-chlorophenylaldehyde (28 mg, 0.2 mmol) followed by treatment with 8N sodium hydroxide (0.5 ml) Lt; / RTI > The pH was adjusted to 7.0, extracted with ethyl acetate (100 ml), and purified by silica gel column and ethyl acetate: hexane = 1: 6 to obtain Compound 10 represented by the following formula 10 (42.6 mg, 66.56% .

[Chemical formula 10]

Detailed NMR data are shown below.

¹ H-NMR (CDCl ₃ ): 7.88 ppm (ddd, J = 8.8 Hz, 4.4 Hz, 2.4 Hz, 1H), 7.77 ppm (d, J = 16 Hz, 2H), 7.61 ppm-7.55 ppm (m, 2H), 7.45 ppm (d, J = 16 Hz, 1H, CH = CH), 7.48 ppm- 7.380 ppm (m, 2H). ESI-MS: m / z calcd for C 15 H 11 ClO [M + H] = 320.97 found 320.9.

Example 11 Synthesis of (E) -3- (4-fluorophenyl) propano-2-en-1- chlorophenyl) -1- (2,6-dihydroxyphenyl) prop-2-en-1-one) (11)

4-Chlorophenyl aldehyde (28 mg, 0.2 mmol) was added to the solution, and then 8N sodium hydroxide (0.5 ml) was added thereto. And the mixture was stirred at room temperature for 24 hours. The pH of the mixture was adjusted to 7.0, and the mixture was extracted with ethyl acetate (110 ml). The extract was purified by a silica gel column and ethyl acetate: hexane = 1: 5 to obtain Compound 11 represented by the following formula 11 (34.5 mg, 62.9% .

(11)

Detailed NMR data are shown below.

¹ H-NMR (CDCl ₃ ): 9.36 ppm (s, 2H), 7.99 ppm (d, J = 15.6 Hz, 1H, CH = CH), 7.80 ppm (d, J = , 7.55 ppm (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.25 ppm (m, 1H), 6.44 ppm (d, J = 8.0 Hz, 2H). ESI-MS: m / z calcd for C 15 H 12 ClO 3 [M + H] = 275.05 found 275.1.

Example 12 Synthesis of (E) -3- (4-chlorophenyl) -1- (2-hydroxy-4,6-dimethoxyphenyl) prop- - (4-chlorophenyl) -1- (2-hydroxy-4,6-dimethoxyphenyl) prop-2-en-1-one)

4-Chlorophenyl aldehyde (28 mg, 0.2 mmol) was added to the solution, and then 8N sodium hydroxide (0.5 mg, 0.2 mmol) was added to the solution. ml) was treated and stirred at room temperature for 24 hours. The pH was adjusted to 7.0, extracted with ethyl acetate, and then purified on a silica gel column and ethyl acetate: hexane = 1: 5 to obtain Compound 12 (41.5 mg, 65.3%) represented by the following Formula 12.

[Chemical Formula 12]

Detailed NMR data are shown below.

¹ H-NMR (CDCl ₃ ): 14.2 ppm (s, 1H), 7.86 ppm (d, J = 15.6 Hz, 1 H, CH = CH), 7.72 ppm (d, J = , 7.53 ppm (d, J = 8.6 Hz, 2H), 7.38 ppm (d, J = 8.8 Hz, 1H), 6.12 ppm ), 3.92 (s, 3H), 3.84 ppm (s, 3H). ESI-MS: m / z calcd for C 17 H 16 ClO 4 [M + H] = 319.07 found 319.1.

[Example 13] (E) -3- (4-chlorophenyl) -1- (2-hydroxyphenyl) Synthesis of 1- (2-hydroxyphenyl) prop-2-en-1-one) (13)

2-Hydroxyacetophenone (27.2 mg, 0.2 mmol) was dissolved in ethyl alcohol (4 ml), followed by addition of 4-chlorophenylaldehyde (28 mg, 0.2 mmol) followed by treatment with 8N sodium hydroxide (0.5 ml) Lt; / RTI > The pH of the mixture was adjusted to 7.0 and then extracted with ethyl acetate. The extract was purified by a silica gel column and ethyl acetate: hexane = 1: 5 to obtain Compound 13 (38.7 mg, 75.0%) represented by the following formula 13.

[Chemical Formula 13]

Detailed NMR data are shown below.

¹ H-NMR (CDCl ₃ ): 12.78 ppm (s, 1H), 7.93 ppm (dd, J = 8 Hz, 1.2 Hz, 1H), 7.99 (d, J = 15.2 Hz, 1H) J = 15.2 Hz, 1H), 7.62 ppm (d, J = 8.4 Hz, 2H), 7.54 ppm (t, J = 8.4 Hz, 1H), 7.43 ppm dd, J = 8.4 Hz, 0.8 Hz, 1H), 6.98 ppm (t, J = 8.0 Hz, 0.8 Hz, 1H). ESI-MS: m / z calcd for C 15 H 12 ClO 2 [M + H] 259.04, found 259.0.

[Example 14] (E) -1,3-bis (4-chlorophenyl) prop-2-ene -1-one) (14) Synthesis of

4-Chloroacetophenone (30.8 mg, 0.2 mmol) was dissolved in ethyl alcohol (4 ml), followed by addition of 4-chlorophenylaldehyde (28 mg, 0.2 mmol) followed by 8 N sodium hydroxide (0.5 ml) Stir at room temperature. The pH was adjusted to 7.0, extracted with ethyl acetate, and then purified on a silica gel column and ethyl acetate: hexane = 1: 6 to obtain Compound 14 (32.8 mg, 59.4%) represented by the following Formula 14.

[Chemical Formula 14]

Detailed NMR data are shown below.

_{^{1 H-NMR (CDCl 3)}} : 7.96 ppm (d, J = 8.8 Hz, 2H), 7.77 ppm (d, J = 16.0 Hz, 1H), 7.58 ppm (d, J = 8.8 Hz, 2H), 7.52 ppm -7.43 ppm (m, 3H), 7.43 ppm-7.38 ppm (m, 2H). ESI-MS: m / z calcd for C 15 H 11 Cl 2 O [M + H] = 277.02 found 277.0.

[Example 15] (E) -3- (4-chlorophenyl) -1- (4-fluorophenyl) Synthesis of 1- (4-fluorophenyl) prop-2-en-1-one) (15)

4-Fluoroacetophenone (27.6 mg, 0.2 mmol) was dissolved in ethyl alcohol (4 ml), followed by addition of 4-chlorophenylaldehyde (28 mg, 0.2 mmol) followed by treatment with 8N sodium hydroxide (0.5 ml) Lt; / RTI > The pH was adjusted to 7.0, extracted with ethyl acetate, and then purified on a silica gel column and ethyl acetate: hexane = 1: 6 to obtain Compound 15 (31.3 mg, 60.2%) represented by the following formula (15).

[Chemical Formula 15]

Detailed NMR data are shown below.

_{^{1 H-NMR (CDCl 3)}} : 8.08 ppm-8.03 ppm (m, 2H), 7.76 ppm (d, J = 15.6 Hz, 1H, CH = CH), 7.57 (d, J = 8.36 Hz, 2H), 7.48 ppm (d, J = 15.6 Hz, 1H, CH = CH), 7.40 ppm (d, J = 8.4 Hz, 2H), 7.18 ppm (m, 2H). ESI-MS: m / z calcd for C 15 H 11 ClFO [M + H] = 261.05 found 261.1.

[Experimental Example 1] Renal cell survival rate experiment

Pancreatic kidney epithelial cells (LLC-PK1, ATCC) were subcultured at 37 ^° C and 5% CO ₂ in DMEM medium, 10% fetal bovine serum and 1% penicillin-streptomycin.

After 5000 cells were injected per well into a 96-well plate, the cells were cultured for 24 hours. Then, the compounds of the above experimental examples were treated with a sample, treated with 25 μM cisplatin, and cultured for 24 hours. Cell viability was confirmed with MTT reagent.

As a result, as shown in FIG. 1, the chalcone derivatives represented by the above Chemical Formulas 1 to 15 (1 to 15 in FIG. 1, respectively) (98% cell viability at 50 μM compared to other derivatives). (In FIG. 1, the X-axis values of each graph represent the dose of each compound and the unit is μM.) The Y axis The values represent cell viability (%). Specific values are shown in Table 1 below. The numbers of chalcone derivatives in the following Table 1 represent the compounds according to the respective formula numbers according to the above examples. (For example, " 1 " represents the compound represented by the formula (1) in the above embodiment)

Chalcone derivative Concentration (μM) activation(%) One 0 60 10 76 25 78 50 79 100 38 200 34 2 0 62 10 63 25 67 50 68 100 64 200 65 3 0 60 10 68 25 79 50 98 100 36 200 32 4 0 60 10 58 25 60 50 82 100 98 200 97 5 0 60 10 60 25 61 50 63 100 67 200 72 6 0 62 10 63 25 60 50 59 100 58 200 57 7 0 60 10 78 25 79 50 58 100 10 200 8 8 0 60 10 62 25 67 50 67 100 82 200 10 9 0 62 10 63 25 74 50 76 100 76 200 78 10 0 61 10 61 25 78 50 78 100 80 200 98 11 0 60 10 62 25 61 50 63 100 65 200 73 12 0 62 10 63 25 60 50 59 100 58 200 59 13 0 60 10 60 25 60 50 26 100 20 200 20 14 0 60 10 70 25 70 50 72 100 80 200 79 15 0 60 10 62 25 70 50 75 100 82 200 61

That is, the chalcone derivative according to one aspect of the present invention has been shown to inhibit kidney damage caused by an anticancer agent. As a result, it was found that the chalcone derivative according to one aspect of the present invention effectively protects the kidney cells from nephrotoxicity caused by the anticancer agent, and these results show that chalcone derivatives protect the kidney cell damage caused by oxidative stress It is also meant to be.

[Experimental Example 2] Image-based cell viability determination

500,000 cells were added to a 10-cm culture plate of the porcine epithelial cells (LLC-PK1) as in Experimental Example 1, and cultured for 24 hours. Then, the compound of Experimental Example was treated as a sample for each concentration and after 2 hours, Lt; / RTI > After that, the cells were stained with PI (propidium iodide) and Annexin V, and the survival rate of the cells was confirmed.

Because PI stained dead cells and annexin V stained live cells, the number of PI cells stained was confirmed and the number of dead cells was confirmed. The results are shown in FIG. 2, which shows that 33% of the cells killed without treatment of the sample were 17% when treated with 25 uM and 7% with 50 uM. That is, it can be clearly seen that when Compound 3 is treated, the light green point tends to decrease.

Hereinafter, a pharmaceutical composition for reducing nephrotoxicity or a formulation example of a food composition containing the chalcone derivative according to one aspect of the present invention will be described in more detail. However, the present invention is not limited thereto. The invention is not limited to the following examples.

[Formulation Example 1] Soft capsule

The soft capsule filling liquid is prepared by mixing 8 mg of the chalcone derivative of the above embodiment, 9 mg of vitamin E, 9 mg of vitamin C, 2 mg of palm oil, 8 mg of vegetable hardened oil, 4 mg of yellow radish and 9 mg of lecithin. 400 mg per capsule is filled to prepare a soft capsule. Separately from this, a soft capsule sheet was prepared in a ratio of 66 parts by weight of gelatin, 24 parts by weight of glycerin and 10 parts by weight of sorbitol, and filled with the filling solution to prepare a soft capsule containing 400 mg of the composition of the present invention.

[Formulation Example 2] Tablets

8 mg of the chalcone derivative of the example, 9 mg of vitamin E, 9 mg of vitamin C, 200 mg of galactooligosaccharide, 60 mg of lactose and 140 mg of maltose were mixed and granulated using a fluidized bed drier, and 6 mg of sugar ester was added. 500 mg of these compositions are tabletted by conventional methods to prepare tablets.

[Formulation Example 3] Drinking agent

8 mg of the chalcone derivative of the example, 9 mg of vitamin E, 9 mg of vitamin C, 10 g of glucose, 0.6 g of citric acid, and 25 g of liquid oligosaccharide are mixed, and 300 ml of purified water is added thereto to fill 200 ml of each bottle. It is filled in a bottle and sterilized at 130 ° C for 4 to 5 seconds to prepare a drink.

[Formulation Example 4]

8 mg of the chalcone derivative of the example, 9 mg of vitamin E, 9 mg of vitamin C, 250 mg of anhydrous crystalline glucose and 550 mg of starch are mixed and formed into granules by using a fluidized bed granulator and filled in a bag to prepare granules.

[Formulation Example 5]

Injection was prepared according to a conventional method according to the composition shown in Table 2 below.

Compounding ingredient content The chalcone derivative of the embodiment 10-50 mg Sterile sterilized water for injection Suitable amount pH adjusting agent Suitable amount

[Formulation Example 6] Health functional food

Health functional foods were prepared according to the compositions shown in Table 3 below by a conventional method.

Compounding ingredient content The chalcone derivative of the embodiment 20 mg Vitamin A acetate 70 μg Vitamin E 1.0 mg Vitamin B1 0.13 mg Vitamin B2 0.15 mg Vitamin B6 0.5 mg Vitamin B12 0.2 μg Vitamin C 10 mg Biotin 10 μg Nicotinic acid amide 1.7 mg Folate 1 50 μg Calcium pantothenate 0.5 mg Ferrous sulfate 1.75 mg Zinc oxide 0.82 mg Magnesium carbonate 25.3 mg Potassium monophosphate 15 mg Dicalcium phosphate 55 mg Potassium citrate 90 mg Calcium carbonate 100 mg Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a component suitable for a health functional food as a preferred embodiment, the compounding ratio may be arbitrarily modified.

[Formulation Example 7] Health drinks

Health drinks were prepared in a conventional manner according to the composition shown in Table 4 below.

Compounding ingredient content The chalcone derivative of the embodiment 1000 mg Citric acid 1000 mg oligosaccharide 100 g Taurine 1g Purified water Balance

The above components are mixed according to a conventional health drink manufacturing method, and the mixture is stirred and heated at 85 DEG C for about 1 hour, and the solution thus prepared is then filtered to sterilize.

Claims (16)

A chalcone derivative having a structure represented by the following formula (16), an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof
[Chemical Formula 16]

Wherein R ₁ is H, OH or OC _n H _{2n + 1} , wherein n is an integer selected from 1 to 5,
R ₂ is H, OH or C _n H _{2n +1} (n is an integer selected from 1 to 5)
R ₃ is H, OC _n H _{2n +1} (n is an integer selected from 1 to 5) or a halogen group,
R ₄ is H, OH or C _n H _{2n +1} (n is an integer selected from 1 to 5)
R ₅ is H, OH or C _n H _{2n +1} (n is an integer selected from 1 to 5)
R ₆ is H or a halogen group,
R ₇ is H, a methyl group or an ethyl group,
R ₈ is H, OC _n H _{2n +1} (n is an integer selected from 1 to 5) or a halogen group,
R ₉ is H, OH or C _n H _{2n + 1} , wherein n is an integer selected from 1 to 5. The method according to claim 1, wherein when at least one of R ₃ , R ₆ and R ₈ is a halogen group, said halogen group is F, Cl, or Br, a chalcone derivative, an isomer thereof, a pharmaceutically acceptable salt thereof, Its solvate. The method according to claim 1,
(E) -3- (2-bromo-4,5-dimethoxyphenyl) -1-phenylprop-2-en-1-one;
(E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (3,4-dimethoxyphenyl) prop-2-en-1-one;
(E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2-hydroxy-5-methylphenyl) prop-2-en-1-one;
(E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2,6-dihydroxyphenyl) prop-2-en-1-one;
(E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2-hydroxy-4,6-dimethoxyphenyl) propo-2-en-1-one;
(E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2-hydroxyphenyl) propo-2-en-1-one;
(E) -3- (4-chlorophenyl) -1-phenylprop-2-en-1-one;
(E) -3- (4-chlorophenyl) -1- (3,4-dimethoxyphenyl) propo-2-en-1-one;
(E) -3- (4-chlorophenyl) -1- (2-hydroxy-5-methylphenyl) propo-2-en-1-one;
(E) -1- (4-bromophenyl) -3- (4-chlorophenyl) prop-2-en-1-one;
(E) -3- (4-chlorophenyl) -1- (2,6-dihydroxyphenyl) propo-2-en-1-one;
(E) -3- (4-chlorophenyl) -1- (2-hydroxy-4,6-dimethoxyphenyl) propo-2-en-1-one;
(E) -3- (4-chlorophenyl) -1- (2-hydroxyphenyl) propo-2-en-1-one;
(E) -1,3-bis (4-chlorophenyl) prop-2-en-1-one; And
(E) -3- (4-chlorophenyl) -1- (4-fluorophenyl) propo-2-en-1-one, an isomer thereof, Acceptable salts, hydrates thereof or solvates thereof. A composition for protecting kidneys comprising chalcone derivatives having the structure of formula (16), isomers thereof, pharmaceutically acceptable salts thereof, hydrates thereof or solvates thereof as an active ingredient
[Chemical Formula 16]

Wherein R ₁ is H, OH or OC _n H _{2n + 1} , wherein n is an integer selected from 1 to 5,
R ₂ is H, OH or C _n H _{2n +1} (n is an integer selected from 1 to 5)
R ₃ is H, OC _n H _{2n +1} (n is an integer selected from 1 to 5) or a halogen group,
R ₄ is H, OH or C _n H _{2n +1} (n is an integer selected from 1 to 5)
R ₅ is H, OH or C _n H _{2n +1} (n is an integer selected from 1 to 5)
R ₆ is H or a halogen group,
R ₇ is H, a methyl group or an ethyl group,
R ₈ is H, OC _n H _{2n +1} (n is an integer selected from 1 to 5) or a halogen group,
R ₉ is H, OH or C _n H _{2n + 1} , wherein n is an integer selected from 1 to 5. A composition for improving kidney disease comprising chalcone derivative having the structure of formula (16), an isomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof as an active ingredient
[Chemical Formula 16]

Wherein R ₁ is H, OH or OC _n H _{2n + 1} , wherein n is an integer selected from 1 to 5,
R ₂ is H, OH or C _n H _{2n + 1} , wherein n is an integer selected from 1 to 5,
R ₃ is H, OC _n H _{2n +1} (n is an integer selected from 1 to 5) or a halogen group,
R ₄ is H, OH or C _n H _{2n + 1} , wherein n is an integer selected from 1 to 5,
R ₅ is H, OH or C _n H _{2n + 1} , wherein n is an integer selected from 1 to 5,
R ₆ is H or a halogen group,
R ₇ is H, a methyl group or an ethyl group,
R ₈ is H, OC _n H _{2n +1} (n is an integer selected from 1 to 5) or a halogen group,
R ₉ is H, OH or C _n H _{2n + 1} , wherein n is an integer selected from 1 to 5. The composition of claim 4 or 5, wherein when at least one of R ₃ , R ₆ and R ₈ is a halogen group, the halogen group is F, Cl, or Br. The method according to claim 4 or 5,
(E) -3- (2-bromo-4,5-dimethoxyphenyl) -1-phenylprop-2-en-1-one;
(E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (3,4-dimethoxyphenyl) prop-2-en-1-one;
(E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2-hydroxy-5-methylphenyl) prop-2-en-1-one;
(E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2,6-dihydroxyphenyl) prop-2-en-1-one;
(E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2-hydroxy-4,6-dimethoxyphenyl) propo-2-en-1-one;
(E) -3- (2-bromo-4,5-dimethoxyphenyl) -1- (2-hydroxyphenyl) propo-2-en-1-one;
(E) -3- (4-chlorophenyl) -1-phenylprop-2-en-1-one;
(E) -3- (4-chlorophenyl) -1- (3,4-dimethoxyphenyl) propo-2-en-1-one;
(E) -3- (4-chlorophenyl) -1- (2-hydroxy-5-methylphenyl) propo-2-en-1-one;
(E) -1- (4-bromophenyl) -3- (4-chlorophenyl) prop-2-en-1-one;
(E) -3- (4-chlorophenyl) -1- (2,6-dihydroxyphenyl) propo-2-en-1-one;
(E) -3- (4-chlorophenyl) -1- (2-hydroxy-4,6-dimethoxyphenyl) propo-2-en-1-one;
(E) -3- (4-chlorophenyl) -1- (2-hydroxyphenyl) propo-2-en-1-one;
(E) -1,3-bis (4-chlorophenyl) prop-2-en-1-one; And
(E) -3- (4-chlorophenyl) -1- (4-fluorophenyl) propo-2-en-1-one. 6. The composition according to claim 4 or 5, wherein the concentration of said chalcone derivative, its isomer, its pharmaceutically acceptable salt, its hydrate or solvate thereof in said composition is from 0.001 μM to 5M. 6. The composition according to claim 4 or 5, wherein the dose of said chalcone derivative, its isomer, its pharmaceutically acceptable salt, its hydrate or its solvate is 0.0001 mg / kg / day to 80 mg / kg / day. 6. The pharmaceutical composition according to claim 4 or 5, wherein the composition is a pharmaceutical composition or a food composition. 5. The composition of claim 4, wherein said kidney protection is kidney protection from nephrotoxicity by a drug. 12. The composition of claim 11 wherein the nephrotoxicity is nephrotoxic by oxidative stress. 6. The composition of claim 5, wherein the renal disease is a renal disease caused by a drug adverse effect. 14. The composition of claim 11 or 13, wherein the drug is an anti-cancer agent. 15. The composition according to claim 14, wherein the anticancer agent is a platinum-based anticancer agent. 6. The method of claim 5,
The kidney disease is selected from the group consisting of nephritis, pyelonephritis, nephrotic syndrome, renal cancer, acute pyelonephritis, chronic pyelonephritis, renal tuberculosis, urinary tract infection, urinary stone, ureter stones, acute renal failure, chronic renal failure, Nephritis, Nephrotic syndrome, pituitary glomerulosclerosis, membranous sinusitis, and membranoproliferative glomerulonephritis.

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