KR20130109495A - Composition for preventing or treating renal disease - Google Patents

Abstract

PURPOSE: A composition containing Dendrobium moniliforme for preventing or treating renal diseases is provided to lessen side effects when the composition is applied to human body and to show less resistance even after long-term use. CONSTITUTION: A composition for preventing or treating renal diseases contains 0.001-10 wt% of a Dendrobium moniliforme extract as an active ingredient. The extract is a C1-C6 alcohol extract of Dendrobium moniliforme. C1-C6 alcohol is methanol or ethanol. The composition is used for reducing serum creatinine. [Reference numerals] (AA) Sell survival rate (%); (BB) Dendrobium monile

Description

Technical Field [0001] The present invention relates to a composition for preventing or treating kidney disease,

The present invention relates to a composition for preventing or treating renal disease, comprising a bark extract as an active ingredient.

The kidneys are the excretory organs of vertebrates that filter out waste products in the blood and send them out in the form of urine.

There are many different toxins that cause kidney toxicity. Chemicals known to cause renal toxicity include antisteroidal antipyretic analgesic anti-inflammatory agents such as phenacetin, aspirin and indomethacin, puromycin, daunomycin, cyclophosphamide, penicillamine, adriamycin, and cisplatin. , Immunosuppressive agents, aminoglycoside antibiotics such as amikacin, gentamycin, gentamycin, kanamycin, neomycin, sisomycin, streptomycin, tobramycin, cephalosporin antibiotics, carbapenem antibiotics, such as mefenenem, Heavy metals such as cadmium, lead, mercury, chromium, and inorganic and organic heavy metal compounds, chloroform, compounds such as D-serine, sulfonamide, 2-bromoethylene, hydrobromide, and mold toxins such as ocaratoxin and citrinin. In most cases, the exact mechanism by which a drug or drug causes kidney toxicity is not known. Many.

Kidneys are the target of toxic substances because the normal adult adult is likely to accumulate toxic substances in the blood because a large amount of blood flows through about 180 L of blood per day. In addition, in the production of urine, urine is temporarily stored in the kidneys, so toxic substances are concentrated and targeted.

Many synthetic preparations have been developed for the prevention or treatment of diseases caused by renal toxicity, but the importance of preparations derived from natural products has been highlighted due to stability issues such as the possibility of side effects occurring in the human body for a long time. .

Accordingly, the inventors of the present invention have found that a natural product, bark, is effective for the prevention or treatment of kidney disease, and the present invention has been completed.

Kumarappan et al., Ren. Fail., V. 30 (3), p. 307-322, 2008

It is an object of the present invention to provide a composition for the prevention or treatment of natural kidney diseases.

In order to accomplish the above object, the present invention provides a composition for preventing or treating kidney disease, comprising a bark extract as an active ingredient.

The composition according to the present invention includes a natural product obtained from nature as an active ingredient, as well as less side effects when applied to the human body, and is unlikely to develop resistance due to long-term use. In particular, since the composition of the present invention has excellent efficacy in the protection of kidney cells, it can be usefully used in the prevention or treatment of kidney disease.

Figure 1 shows the antioxidant activity of the bark extract.
Fig. 2 is an evaluation of the ability of the bark extract to protect kidney cells.

In one aspect, the present invention relates to a composition for preventing or treating renal disease, which comprises a bark extract as an active ingredient.

Herein seokgok (Dendrobium moniliforme ) refers to perennial herbaceous plants belonging to the Orchidaceae family. It grows to 20 to 50 cm and grows in Korea, Japan, and China. In oriental medicine, the whole plant except the root is called Seokgok, and when it blooms in summer, it cuts out the outpost and dries it in the sun and uses it as a medicinal herb. The bark used in the present specification may be contained in the form of an extract, or may be contained as a pulverized product of the herbal medicine itself, or as a dried pulverized product of a herbal medicine, but is not limited thereto. The grains used in the present invention are not limited to the method of obtaining the grains, and may be cultivated or used by purchasing commercially available grains. Some or all of the ground portions of the herbal can be used, and preferably all of the ground portions can be used have.

In the composition for preventing or treating kidney disease, which is an aspect of the present invention, the bark extract may contain a bark-C ₁ -C ₆ alcohol extract, and may be a bark-methanol extract or a bark-ethanol extract .

As used herein, the bark extract may be a crude extract of a solvent selected from the group consisting of water, C ₁ -C ₆ alcohols, and combinations thereof. The C ₁ -C ₆ alcohol may specifically be methanol or ethanol. When extracting the gravel with a solvent, it is preferable to extract by adding a solvent corresponding to about 5 to 15 times of the gravel, and specifically, about 10 times the amount of the solvent is preferably added, but the present invention is not limited thereto. The extraction may be a heat extraction, cold extraction, reflux cooling extraction, or ultrasonic extraction, and the like, there is no limitation if the extraction is obvious to those skilled in the art. The extraction may be performed at room temperature, but for more efficient extraction, the extraction may be performed under heating conditions, preferably at about 40 to 100 ° C., more preferably at about 80 ° C., but is not limited thereto. It is not. The extraction time is preferably about 2 to 4 hours, more preferably about 3 hours, but is not limited thereto, and may vary depending on conditions such as extraction solvent and extraction temperature. The extraction may be extracted one or more times several times in order to obtain a larger amount of the active ingredient, preferably one to five times, more preferably three times the continuous extraction can be used combined extract.

In this specification, the bark extract may contain a crude extract of bark, as described above, and may be included as a soluble fraction of an organic solvent obtained by further extracting the crude extract with an organic solvent having a low polarity. Examples of the organic solvent include, but are not limited to, hexane, methylene chloride, ethyl acetate, n-butanol, and the like. The extract or the soluble fraction of the extract may be used as it is, or may be used as an extract form by concentration after filtration, and may be used as a form of a lyophilizate by concentration and freeze-drying.

In the composition for preventing or treating kidney disease according to one aspect of the present invention, the bark extract may be contained in an amount of 0.001 to 10% by weight based on the total weight of the composition. If the bark extract is contained in an amount of less than 0.001% by weight based on the total weight of the composition, the effect on the kidney disease is insignificant, and if it exceeds 10% by weight, the content of other constituents on the drug is limited. In such a viewpoint, the bark extract may contain 0.0011 to 9 wt%, 0.0012 to 8 wt%, 0.0013 to 7 wt%, 0.0014 to 6 wt%, 0.0015 to 5 wt%, 0.0016 to 4 wt% %, 0.0017 to 3 wt.%, 0.0018 to 2 wt.% Or 0.0019 to 1 wt.%, And more specifically 0.002 wt.%, But not limited thereto.

In the composition for preventing or treating kidney disease, which is an aspect of the present invention, the composition may include lowering creatinine in the blood.

In the present specification, creatinine is a substance generated from creatine present in muscle, and the daily output is constant in proportion to the amount of muscle. Urinary excretion of creatinine is proportional to glomerular filtration, and blood concentration of creatinine can be used as an indicator of renal function. The normal value is about 1 mg / dl. In kidney disease, the level of creatinine in the blood rises. In the present specification, lowering the creatinine level in blood means normally lowering the level higher than the normal creatinine level.

In the composition for preventing or treating kidney disease, which is an aspect of the present invention, the kidney disease may be a disease induced by renal toxicity due to oxidative stress. In the present specification, the oxidative stress may be due to oxidative damage caused by free radicals and / or deterioration of an antioxidant defense system in vivo. In the present specification, the kidney disease may be a disease according to kidney toxicity caused by destruction of kidney cells due to oxidative stress.

In the composition for the prevention or treatment of kidney disease, which is an aspect of the present invention, the kidney disease is nephritis, pyelonephritis, nephrotic syndrome, kidney cancer, acute pyelonephritis, chronic pyelonephritis, kidney tuberculosis, urinary tract infection, urolithiasis, ureteral stone , Acute renal failure, chronic renal failure, diabetic nephropathy, chronic glomerulonephritis, acute progressive nephritis, neproje syndrome, microglomerulosclerosis, mesothelial nephropathy, or membranous proliferative glomerulonephritis.

In a composition for preventing or treating renal disease, which is an aspect of the present invention, the composition may be for antioxidation. The composition of the present invention may be an antioxidant for preventing the oxidation of kidney cells and preventing the destruction of kidney cells.

In the composition for preventing or treating kidney disease, which is an aspect of the present invention, the composition may be a health food composition.

The composition may be processed into a drink, fermented milk, cheese, yogurt, juice, probiotic agent, and health supplement food or the like, and may be used in various other food additives.

In one embodiment, the composition may contain other ingredients and the like that can give a synergistic effect to the main effect within a range that does not impair the main effect of the present invention. For example, additives such as perfume, coloring agent, bactericide, antioxidant, preservative, moisturizing agent, thickening agent, inorganic salt, emulsifier and synthetic polymer substance may be further added for improvement of physical properties. In addition, supplementary ingredients such as water soluble vitamins, oil soluble vitamins, polymer peptides, polymer polysaccharides and seaweed extract may be further included. The above components may be mixed and selected without difficulty by those skilled in the art depending on the purpose of formulation or use, and the amount thereof may be selected within a range that does not impair the objects and effects of the present invention.

The composition according to the present invention may be in various forms such as a solution, an emulsion, a viscous mixture, a tablet, a powder, etc., and may be administered by various methods such as simple drinking, injection administration, spraying or squeezing.

In the composition for the prevention or treatment of kidney disease, which is an aspect of the present invention, the composition may be a pharmaceutical composition.

In one embodiment, the pharmaceutical composition may be a pharmaceutical composition effective for kidney disease, and specifically, may be a pharmaceutical composition effective for kidney disease caused by oxidative stress. Specifically, the pharmaceutical composition is nephritis, pyelonephritis, nephrotic syndrome, kidney cancer, acute pyelonephritis, chronic pyelonephritis, kidney tuberculosis, urinary tract infections, urinary tract stones, ureteral stones, acute kidney failure, chronic kidney failure, diabetic nephropathy, chronic glomeruli It may be a pharmaceutical composition effective for the prevention, alleviation or treatment of symptoms of nephritis, including nephritis, acute progressive nephritis, nephropathy syndrome, microglomerular sclerosis, mesothelial nephropathy, or mesenchymal glomerulonephritis.

When the composition according to the present invention is applied to medicines, it may be formulated into an oral or parenteral dosage form in the form of solid, semi-solid or liquid by adding an inorganic or organic carrier to the composition as an active ingredient.

Examples of the preparation for oral administration include tablets, pills, granules, soft and hard capsules, powders, fine granules, powders, emulsions, syrups, pellets, and the like. Can be mentioned. In addition, preparations for parenteral administration include injections, drops, ointments, lotions, sprays, suspensions, emulsions, suppositories, and the like. In order to formulate the active ingredient of the present invention, it can be easily formulated according to the conventional method, and surfactants, excipients, coloring agents, spices, preservatives, stabilizers, buffers, suspensions, and other commonly used auxiliaries can be suitably used.

The pharmaceutical composition according to the present invention may be administered orally, parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously and the like.

In addition, the dosage of the active ingredient will vary depending on the age, sex and weight of the subject to be treated, the specific disease or pathology to be treated, the severity of the disease or pathology, the route of administration and the judgment of the prescriber. Dosage determinations based on these factors are within the level of those skilled in the art. Typical dosages are from 0.001 [mu] g / kg / day to 2000 [mu] g / kg / day, more specifically from 0.5 [mu] g / kg / day to 1500 [mu] g / kg / day.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for illustrating the present invention and that the scope of the present invention is not construed as being limited by these embodiments.

[ Example  One] Seokgok  Preparation of extract

The gypsum used in the present invention was purchased and used on herbal medicines in Kyungdong market, Seoul, Korea.

[ Example  1-1] Seokgok - Preparation of water extract

4 Kg of granite ground was immersed in 40 L of water and sonicated for 3 hours. The extraction was repeated three times. The extract was dried under reduced pressure and concentrated to give 195 g of concentrate.

[ Example  1-2] Seokgok - Preparation of methanol extract

4 Kg of granite ground parts were soaked in 40 L of 100% methanol and ultrasonically extracted for 3 hours. The extraction was repeated three times. The extract was dried under reduced pressure and concentrated to give 220 g of concentrate.

[ Example  1-3] Seokgok - Preparation of ethanol extract

4 Kg of the tops of the granite trees were soaked in 40 L of 100% ethanol and ultrasonically extracted for 3 hours. The extract obtained by repeating this three times was dried under reduced pressure and concentrated to obtain 205 g of a concentrate.

[ Example  2] Seokgok  Extract Antioxidant ability  evaluation

DPPH (α-α-diphenyl-β-picrylhydrazyl) radical scavenging activity was measured for the methanol extract of bark. The DPPH radical scavenging activity measurement method is a stable free radical having nonspecific electrons. When DPPH exhibiting the maximum absorption value at around 517 nm receives electrons or hydrogen, the absorbance decreases around 517 nm. Therefore, it is measured to measure antioxidative activity and other radicals (Hatano et al., Chem. Pharm. Bull., 38 (5), pp1224-1229, 1990).

100 μL of 60 μM DPPH (α-α-diphenyl-β-picrylhydrazyl) was added to 100 μL of the bovine methanol extract prepared at concentrations of 6.25, 12.5, 25, 50 and 100 μg / mL. After stirring for 30 minutes, absorbance at 540 nm Were measured. The antioxidative activity (electron donating ability) was confirmed by measuring the absorbance reduction rate of the control group in which nothing was treated and the extract of bamboo grass methanol produced according to Example 1-2.

As a result (FIG. 1), the methanol extract of bark showed excellent DPPH radical scavenging ability in a concentration dependent manner, and thus the composition according to the present invention was confirmed to have excellent electron donating ability.

[ Example  3] Seokgok  Extract kidney cells Protection ability  evaluation

The LLC-PK1 cell line, which is a kidney cell, is susceptible to oxidative damage. A radical scavenger, AAPH (2,2'-Azobis (1-aminopropane) dihydrochloride), binds very rapidly with oxygen molecules to form peroxyl radical (Miki et al., Arch. Biochem. Biophy., 258 (2), 373-380, 1987) by inducing lipid peroxidation. Renal protective activity can be assessed using oxidative damage of LLC-PK1 cell lines using AAPH. In this example, kidney cells (LLC-PK1) were used to evaluate the protective effect against renal toxicity according to the following experimental methods reported in the literature (Yokozawa et al., Food Chem., 48, pp5068-5073, 2000) .

First, LLC-PK1 cells were treated with 5% fetal bovine serum (Gibco BRL Life Technologies), penicillin G 50 units / ml (Gibco BRL Life Technologies) and streptomycin (Grepcocin B. Incubated in a 95% air / 5% carbon dioxide incubator maintained at 37 ° C using DMEM / F12 (Gibco BRL Life Technologies, Grand Island, NY, USA) medium added. Cultured LLC-PK1 cells were introduced 10 ^{4 4} into 96-well culture plates and allowed to stabilize for 2 hours.

Subsequently, the extract of bovine methanol (1, 10 μg / m 2) prepared according to Example 1-2 and a radical generating reagent (10 mM AAPH dissolved in the medium) were added and cultured for 24 hours. Then 50 μl of MTT / mL) reagent was added to each well, followed by incubation at 37 ° C. After 4 hours, the medium containing MTT was removed and 100 μl of dimethylsulfoxide was added thereto. The absorbance was measured using a 540 nm detection wavelength in a SPECTRAmax 340PC (Molecular Devices, Sunnyvale, Calif., USA) microplate reader And the survival rate of the cells was measured.

As a result (Fig. 2), treatment with 10 mM AAPH reduced the number of LLC-PK1 cells to 72% of the AAPH-untreated group, whereas the bark extract of methanol inhibited such cell damage. At a concentration of 10 μg / mL AAPH decreased the number of cells to normal levels.

These results indicate that bark extracts can protect kidney cell damage caused by oxidative stress.

[ Example  4] Seokgok  Blood creatinine of the extract Descent  evaluation

[ Example  4-1] Experimental group  Set

After 7 weeks of high - fat diet using C57BL / 6 mouse (SPL), effects of each drug used as a herb extract and control group on the metabolic enhancement efficacy were evaluated. Metformin was used as a positive control.

(AIN-76A, 40%). The mice were divided into 5 groups after 1 week of adaptation in the laboratory. The mice were divided into two groups: ⅰ) normal diet (Purina rat diet, beef tallow), and iii) metformin group and metformin group (500 mg / Kg) were given high-fat diet, and iv) high-fat diet and 200 mg / kg of bark extract obtained in Example 1 The group was made into the Kogok group. Each drug was suspended orally in 0.8% methylcellulose solution and administered orally every day for 8 weeks.

[ Example  4-2] Analysis of blood creatinine concentration

 Serum creatinine concentration is the most important indicator of renal function and is widely used clinically. Mice in each group fasted for 16 hours after the administration according to Example 4-1 were anesthetized with ether, and whole blood was obtained through the abdominal artery. Serum creatinine concentration was then measured using plasma. Serum creatinine concentration was measured using the rate blank Jaffe Kinetic method, creatinine (Roche, USA) reagent and hitachi modular (Japan) instrument.

As a result (Table 1), it was confirmed that the herbaceous group lowered the serum creatinine level by 23% or more compared to the high-fat diet group.

Volume
(mg / kg body-weight / day)
Creatinine (mg / dL)
Untreated group - 0.10 0.02
It's a high-fat diet. - 0.18 ± 0.01 Metformin group 500 0.11 + - 0.01 Seokgok-gun 200 0.14 ± 0.01

Examples of the formulation of the composition will be described below, but are not intended to limit the present invention but merely to be described in detail.

Formulation Example 1 Soft Capsule

A soft capsule filling liquid is prepared by mixing 80 mg of bark extract, 9 mg of vitamin E, 9 mg of vitamin C, 2 mg of palm oil, 8 mg of vegetable hardening oil, 4 mg of yellowing powder and 9 mg of lecithin and mixing them according to a conventional method. 400 mg per capsule is filled to prepare a soft capsule. In addition, a soft capsule sheet is prepared at a ratio of 66 parts by weight of gelatin, 24 parts by weight of glycerine, and 10 parts by weight of sorbitol solution and filled with the filler to prepare a soft capsule containing 400 mg of the composition according to the present invention.

[Formulation Example 2] Tablets

After mixing with 80 mg of bark extract, 9 mg of vitamin E, 9 mg of vitamin C, 200 mg of galactooligosaccharide, 60 mg of lactose and 140 mg of maltose, granulate using a fluid bed drier and add 6 mg of sugar ester. Tablets are prepared by tableting 500 mg of these compositions in a conventional manner.

[Formulation Example 3] Drinks

After mixing 80 mg of bark extract, 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, 300 ml of purified water is added and filled 200 ml each bottle. After filling the bottle sterilized for 4-5 seconds at 130 ℃ to prepare a drink.

[Formulation Example 4]

80 mg of bark extract, 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 using a fluidized bed granulator and filled in a vial to prepare granules.

Formulation Example 5 Injection

Bark extract .................................. 20 mg

Sterile Distilled Water for Injection ...

pH adjuster ...

Injections are prepared in the above amounts per ampoule (2 ml) according to the conventional method for preparing injections.

Those skilled in the art will appreciate that various modifications, additions and substitutions are possible, without departing from the scope and spirit of the invention as disclosed in the accompanying claims.

Preparation Example 6 Preparation of Healthy Drinks

Calyx extract ................................... 1000 mg

Citric acid ................................................. ... 1000 mg

oligosaccharide................................................. .... 100 g

Plum concentrate ................................................ ..... 2 g

Taurine ................................................. ........... 1 g

Purified water was added to the mixture to complete 900 ml

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, ≪ / RTI >

Although the composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and use purpose. Those skilled in the art to which the present invention pertains will be able to perform various applications and modifications within the scope of the present invention based on the above contents.

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. something to do. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (10)

A composition for the prevention or treatment of kidney disease comprising a stone extract as an active ingredient. The composition for preventing or treating kidney disease of claim 1, wherein the Seokgok extract is Seokgok-C ₁ ~ C ₆ alcohol extract. The composition for preventing or treating kidney disease of claim 2, wherein the alcohol is methanol or ethanol. The composition for preventing or treating kidney disease according to claim 1, wherein the stone extract is contained in an amount of 0.001 to 10% by weight based on the total weight of the composition. The composition for preventing or treating kidney disease according to claim 1, wherein the composition is for lowering creatinine in the blood. According to claim 1, wherein the kidney disease is a disease induced by renal toxicity caused by oxidative stress, composition for the prevention or treatment of kidney disease. According to claim 6, The kidney disease is nephritis, pyelonephritis, nephrotic syndrome, kidney cancer, acute pyelonephritis, chronic pyelonephritis, kidney tuberculosis, urinary tract infections, urinary tract stones, ureteral stones, acute kidney failure, chronic kidney failure, diabetic nephropathy, A composition for the prophylaxis or treatment of kidney disease, including chronic glomerulonephritis, acute progressive nephritis, nephropathy syndrome, microglomerulosclerosis, mesothelial nephropathy, or membranous proliferative glomerulonephritis. The composition for preventing or treating kidney disease according to claim 1, wherein the composition is for antioxidant. The composition for preventing or treating kidney disease according to any one of claims 1 to 8, wherein the composition is a health food composition. The composition for preventing or treating kidney disease according to any one of claims 1 to 8, wherein the composition is a pharmaceutical composition.

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