KR20210003530A - Composition for preventing, ameliorating or treating hyperuricemia or metabolic disorders associated with hyperuricemia comprising egg shell membrane as effective component - Google Patents

Abstract

The present invention relates to a composition for preventing, alleviating or treating hyperuricemia or hyperuricemia-associated metabolic disorders, containing eggshell membrane as an active component. The eggshell membrane, which is the active component of the present invention, has effects of reducing the amount of uric acid in the serum, increasing the amount of uric acid to be excreted into the urine, and reducing the amounts of BUN and creatinine in the serum. Therefore, the composition of the present invention can be used as a health functional food or medicine for preventing, alleviating or treating hyperuricemia or hyperuricemia-associated metabolic disorders.

Description

Composition for preventing, ameliorating or treating hyperuricemia or metabolic disorders associated with hyperuricemia comprising egg shell membrane as effective component}

The present invention relates to a composition for preventing, improving or treating metabolic disorders related to hyperuricemia or hyperuricemia, containing the egg shell membrane as an active ingredient.

Hyperuricemia is defined by blood uric acid values greater than 6.8-7.0 mg/dL in men or greater than 6 mg/dL in women. Hyperuricemia and hyperuricemia related metabolic disorders (eg gout) occur in 3 to 5 million people in the United States. In the United States, African-Americans are twice as likely to have gout than whites. In addition, gout and hyperuricemia are prevalent in China, Japan, Polynesia, and urban sub-Saharan Africa, and the incidence of gout approximately doubled between 1990 and 2010, and the number of gout patients in Korea increased by an annual average of 14%. It is a trend.

Metabolic disorders related to hyperuricemia include gout, as well as uric acid crystals, deposits of urate crystals in the joints, acute, monoarticular, inflammatory arthritis pain attacks due to deposits of urate crystals in the kidneys, urolithiasis, nephrolithiasis and gout. This includes nephropathy. Long-term nephrolithiasis and gouty nephropathy are known to increase the risk of kidney damage and kidney failure. Among metabolic disorders related to hyperuricemia, gout is a form of urate (uric acid is present in the blood, body fluids, and joint fluids) as the concentration of uric acid (a product left after the body metabolizes a substance called purine ingested through food) increases in the blood. It is a disease in which crystals are deposited on the cartilage, tendons, and surrounding tissues of the joint. This phenomenon induces joint inflammation and causes recurrent seizures accompanied by extreme pain, and as tophi is deposited by urate crystals, joint deformity and disability occur. In addition to joint abnormalities, nephroolithiaisis (nephrolithiasis), which causes various kidney diseases and stones in the kidneys due to uric acid, may also appear.

In addition, gout appears through stages such as asymptomatic hyperuricemia, acute gouty arthritis, intermittent gout, and chronic nodular gout. Asymptomatic hyperuricemia, which appears in the early stages, increased serum uric acid concentration, but symptoms such as arthritis, gout nodules, and uric acid renal disease have not yet been observed. Acute gouty arthritis is a stage in which gout attacks or kidney stones develop, usually after hyperuricemia, which lasts for at least 20 years, and the most characteristic symptom is an acute attack of very painful arthritis. It is invasive, and there are no systemic symptoms, but it gradually invades several joints and accompanies fever. Intermittent gout refers to the period without symptoms between gout attacks. Most of them experience a second attack between 6 months and 2 years after the first attack, depending on the treatment, but gradually increase in frequency and multiple joints. Will invade. Chronic nodular gout appears similar to other types of arthritis when the period of chronic nodular gout passes through an intermittent period without gout. Progressive stiffness and persistent pain occur in the joint at the affected site.

Gout is known for its clear and successful treatment, but it is often accompanied by other diseases such as high blood pressure and chronic kidney failure, so it is often necessary to carefully consider the side effects of drugs, and as a non-drug treatment, lifestyle changes are made. Efforts of the patient to be given are essential to a good prognosis for long-term treatment. Gout and hyperuricemia show clinical features such as high blood pressure, hyperlipidemia, increased blood sugar, and abdominal obesity, and do not meet the diagnostic criteria for metabolic syndrome, which is a complex condition that increases the risk of adult diseases such as atherosclerotic heart disease and type 2 diabetes. Metabolic syndrome is thought to have a close relationship. In Korea, it was reported that 44% of gout patients had metabolic syndrome. Gout usually appears in the form of acute monoarthritis, but it may involve minor joints or, rarely, multiple joints. Non-steroidal anti-inflammatory drugs (NSAIDs) used in the treatment of acute gout are well known to inhibit inflammatory reactions, and colchicine, which exhibits anti-inflammatory effects by inhibiting the activity and movement of leukocytes. , Steroids are all drugs that can effectively treat gout attacks, and selective cyclooxygenase (COX-2) inhibitors are also known to have the same effects as conventional nonsteroidal anti-inflammatory drugs.

On the other hand, the egg shell membrane is the membrane on the inside of the egg shell of the bird, and consists of two inside and outside, the outer shell membrane is in close contact with the inner surface of the egg shell, and the inner shell membrane encloses the egg white. The egg shell membrane is made of a strong fibrous protein, and is mainly composed of ovo keratin and ovo mucin. Eggshell membranes are known to have a function of promoting skin regeneration, as they have been used for measures such as abrasions in a wrestling room for a long time. Recently, the production of (III) type collagen, also called fetal collagen. It has been reported to have an action to promote.

Korean Patent Application Publication No. 2015-0116913 discloses the use of an egg shell membrane preparation for relieving joint pain, and Korean Patent Application Publication No. 2018-0063091 discloses the nuclear factor kappa-light chain of activating B cell regulation disorder using the egg shell composition. A method for activating the enhancer (NF-κB) in a host requiring it is disclosed, and in Korean Patent No. 1894478, a scrub cosmetic composition comprising a quail egg shell membrane pulverized product, and a quail egg shell membrane pulverized product for a scrub cosmetic A method and a pulverized product of quail egg shell membrane for a scrub cosmetic according thereto are disclosed. However, there is no disclosed composition for the prevention, improvement or treatment of metabolic disorders related to hyperuricemia or hyperuricemia containing the egg shell membrane of the present invention as an active ingredient.

The present invention provides a composition for preventing, improving or treating metabolic disorders related to hyperuricemia or hyperuricemia containing the egg shell membrane as an active ingredient, and the egg shell membrane as an active ingredient of the present invention By reducing the amount of uric acid in the blood, increasing the amount of uric acid excreted into urine, and confirming that there is an effect of reducing the amount of blood BUN and creatinine, the present invention was completed.

In order to achieve the above object, the present invention provides a health functional food composition for preventing or improving hyperuricemia or metabolic disorders related to hyperuricemia, comprising an egg shell membrane as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of metabolic disorders related to hyperuricemia or hyperuricemia comprising the egg shell membrane as an active ingredient.

The present invention relates to a composition for preventing, improving or treating metabolic disorders related to hyperuricemia or hyperuricemia, containing the egg shell membrane as an active ingredient. The egg shell membrane, an active ingredient of the present invention, has the effect of reducing the content of uric acid in the serum and increasing the amount of uric acid excreted into the urine, and has the effect of reducing the content of BUN and creatinine in the serum.

1 is a result of confirming the amount of uric acid in serum after oral administration of the egg shell membrane of the present invention once. Normal: Normal group, Control: Control group (150mg/kg potassium oxonate administration group), EM 100mg/kg, EM 200mg/kg: 100mg/kg or 200mg/kg egg shell membrane administration group, Allopurinol 10mg/kg: 10mg/kg as positive control This is the allopurinol administration group. ### indicates that the amount of uric acid in the serum of the control group was statistically significantly increased compared to the normal group, p<0.001, and *** indicates that the amount of uric acid in the serum of the egg shell membrane administration group or the positive control group was statistically significantly decreased compared to the control group. , p<0.001.
2 is a result of confirming the amount of uric acid in the serum after oral administration of the egg shell membrane of the present invention for 5 days. Normal: Normal group, Control: Control group (150mg/kg potassium oxonate administration group), EM 100mg/kg, EM 200mg/kg: 100mg/kg or 200mg/kg egg shell membrane administration group, Allopurinol 10mg/kg: 10mg/kg as positive control Allopurinol administration group of, Benzbromarone 50mg/kg is a positive control group, and 50mg/kg benzobromarone administration group. ## indicates that the amount of uric acid in the serum of the control group was statistically significantly increased compared to the normal group, p<0.01, and *, **, *** indicates the amount of uric acid in the serum of the egg shell membrane administration group or the positive control group compared to the control group. Decreased, * is p<0.05, ** is p<0.01, and *** is p<0.001.
3 is a result of confirming the amount of uric acid in urine after oral administration of the egg shell membrane of the present invention for 5 days. Normal: Normal group, Control: Control group (150mg/kg potassium oxonate administration group), EM 100mg/kg, EM 200mg/kg: 100mg/kg or 200mg/kg egg shell membrane administration group, Allopurinol 10mg/kg: 10mg/kg as positive control Allopurinol administration group of, Benzbromarone 50mg/kg is a positive control group, and 50mg/kg benzobromarone administration group. # Represents a statistically significant decrease in the amount of uric acid in the urine of the control group compared to the normal group, p<0.05, and * represents a statistically significant increase in the amount of uric acid in the urine of the egg shell membrane administration group or the positive control group compared to the control group, p<0.05 to be.
4 is a result of confirming the BUN content in serum after oral administration of the egg shell membrane of the present invention for 5 days. Normal: Normal group, Control: Control group (150mg/kg potassium oxonate administration group), EM 200mg/kg: 200mg/kg egg shell membrane administration group, Allopurinol 10mg/kg: 10mg/kg allopurinol administration group as a positive control, Benzbromarone 50mg/kg Is a positive control group administered with 50 mg/kg of benzobromarone. # Is a statistically significant increase in the serum BUN content of the control group compared to the normal group, p<0.05, *, ** indicates that the serum BUN content of the egg shell membrane administration group or the positive control group was statistically significantly decreased compared to the control group. Where * is p<0.05, ** is p<0.01.
5 is a result of confirming the content of creatinine in serum after oral administration of the egg shell membrane of the present invention for 5 days. Normal: Normal group, Control: Control group (150mg/kg potassium oxonate administration group), EM 200mg/kg: 200mg/kg egg shell membrane administration group, Allopurinol 10mg/kg: 10mg/kg allopurinol administration group as a positive control, Benzbromarone 50mg/kg Is a positive control group administered with 50 mg/kg of benzobromarone. * Indicates that the serum creatinine content of the egg shell membrane administration group or the positive control group was statistically significantly decreased compared to the control group, p<0.05.

The present invention relates to a health functional food composition for preventing or improving hyperuricemia or metabolic disorders related to hyperuricemia comprising the egg shell membrane as an active ingredient.

The hyperuricemia-related metabolic disorder is preferably any one selected from acute or chronic gout, gouty redness, gouty arthritis, gouty nephrolithiasis, and gouty nephropathy, but is not limited thereto.

The egg shell membrane may be an algae shell membrane, and is preferably an egg shell membrane obtained from at least one selected from eggs, quail eggs, duck eggs and ostrich eggs, but is not limited thereto. Although the egg shell membrane is not particularly distinguished, it is a membrane inside the egg shell, and is preferably used in the form of powder, but is not limited thereto.

The composition is preferably prepared in any one formulation selected from powder, granule, pill, tablet, capsule, candy, syrup and beverage, but is not limited thereto.

Examples of foods to which the egg shell membrane of the present invention can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea , Drinks, alcoholic beverages, and may be in any one form selected from a vitamin complex, and includes all health foods in the usual sense.

The health functional food includes various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, coloring agents and enhancers (cheese, chocolate, etc.), pectic acid and salts thereof, alkynic acid and salts thereof, organic acids, protective colloid thickeners. , pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonates used in carbonated beverages, and the like. In addition, it may contain pulp for the manufacture of natural fruit juices and vegetable beverages. These components may be used independently or in combination.

The health functional food of the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients. The natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetener, natural sweeteners such as taumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame may be used.

In addition, the present invention relates to a pharmaceutical composition for the prevention or treatment of metabolic disorders related to hyperuricemia or hyperuricemia comprising the egg shell membrane as an active ingredient.

In the pharmaceutical composition, the metabolic disorder related to hyperuricemia is preferably any one selected from acute or chronic gout, gouty redness, gouty arthritis, gouty nephrolithiasis, and gouty nephropathy, but is not limited thereto. The gouty redness refers to a symptom of redness due to inflammation caused by gout.

In addition to the active ingredient, a urate-lowering agent may additionally be included, and the preferred urate-lowering agent is one or more selected from a xanthine oxidase inhibitor, a uric acid excretion accelerator, a urate oxidase, a urine alkalizing agent, and fenofibrate, but is not limited thereto. In addition to the egg shell membrane, a pharmaceutically acceptable carrier, excipient, or diluent may be further included.

The pharmaceutical composition of the present invention may be in various oral or parenteral dosage forms. In the case of formulation, it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants that are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient in one or more compounds, such as starch, calcium carbonate, sucrose, or lactose ( lactose), gelatin, etc. In addition, in addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, syrups, etc.In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweetening agents, fragrances, and preservatives may be included. have. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin, glycerol, gelatin, and the like may be used.

The composition of the present invention may be administered orally or parenterally, and when administered parenterally, it is preferable to select an injection method for external use of the skin or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injection.

The composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is the type of disease, severity, and drug activity of the patient. , Sensitivity to drugs, time of administration, route of administration and rate of excretion, duration of treatment, factors including drugs used concurrently, and other factors well known in the medical field. The composition of the present invention may be administered as an individual therapeutic agent or administered in combination with other therapeutic agents, may be administered sequentially or simultaneously with a conventional therapeutic agent, and may be administered single or multiple. It is important to administer an amount capable of obtaining the maximum effect in a minimum amount without side effects in consideration of all the above factors, and this can be easily determined by a person skilled in the art.

The dosage of the composition of the present invention can be used in various ranges according to the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate, and severity of disease.

Hereinafter, the present invention will be described in more detail using examples. These examples are only for describing the present invention in more detail, and it is apparent to those of ordinary skill in the art that the scope of the present invention is not limited thereto.

Example One. Koyosan Blood uric acid lowering effect in animal model

(1) Eggshell membrane administration 1 day

In order to induce hyperuricemia in an animal model, a solution of 0.5% sodium carboxymethylcellulose (CMC-Na, pH 5.0) containing 0.1M sodium acetate was added to a 7-week-old male SD-rat. Dissolved 150mg/kg of potassium oxonate was injected intraperitoneally. 1 hour after intraperitoneal injection of potassium oxonate, 100 mg/kg or 200 mg/kg of egg shell powder and 10 mg/kg of allopurinol as a positive control were added to 0.01 M PBS containing 0.1% of polyoxyethylene sorbitane monooleate. (phosphate buffered saline) was suspended in a buffer solution and administered orally once. Two hours after oral administration, after anesthesia with an anesthetic (Entoval), blood was taken and the amount of uric acid was measured using a uric acid assay kit (Biovision, USA).

As a result, as disclosed in FIG. 1, the amount of uric acid in the serum of the potassium oxonate-administered group was significantly increased, and in the group to which the egg corneal powder and allopurinol (positive control) of the present invention were administered orally, statistically significantly decreased.

(2) 5 days of egg shell membrane administration

In order to induce hyperuricemia in an animal model, a solution of 0.5% sodium carboxymethylcellulose (CMC-Na, pH 5.0) containing 0.1M sodium acetate was added to a 7-week-old male SD-rat. Dissolved 150mg/kg of potassium oxonate was injected intraperitoneally. 1 hour after intraperitoneal injection of potassium oxonate, 100 mg/kg or 200 mg/kg of egg shell powder, positive control 10 mg/kg of allopurinol and 50 mg/kg of Benzbromarone 0.1% polyoxyethylene sorbitan monooleate (Polyoxyethylene sorbitane monooleate) was suspended in a 0.01 M phosphate buffered saline (PBS) buffer solution and oral administration was performed once daily for 5 days. Two hours after the final oral administration, after anesthesia with an anesthetic (Entoval), blood was taken and the amount of uric acid was measured using a uric acid assay kit (Biovision, USA).

As a result, as disclosed in FIG. 2, the amount of uric acid in the serum of the potassium oxonate-administered group was significantly increased, and the egg shell membrane powder, allopurinol, and benzbromarone (positive control) of the present invention were orally administered for 5 days. It was confirmed that it decreased significantly.

Example 2. Koyosan Measurement of uric acid in urine in animal models

In order to induce hyperuricemia in an animal model, a solution of 0.5% sodium carboxymethylcellulose (CMC-Na, pH 5.0) containing 0.1M sodium acetate was added to a 7-week-old male SD-rat. Dissolved 150mg/kg of potassium oxonate was injected intraperitoneally. One hour after intraperitoneal injection of potassium oxonate, 100 mg/kg or 200 mg/kg of egg shell powder and positive control 10 mg/kg of allopurinol and 50 mg/kg of Benzbromarone were added to 0.1% of polyoxyethylene sorbitan monooleate. It was suspended in a 0.01M phosphate buffered saline (PBS) buffer solution containing (polyoxyethylene sorbitane monooleate) and administered orally for 5 days.

Thereafter, in order to measure the amount of uric acid in urine, as described above, an experimental animal administered with potassium oxonate and egg shell membrane powder was placed in a metabolic cage to collect urine for 24 hours, and a uric acid assay kit (ab65344, abcam, USA) was used. The amount of uric acid was measured using.

As a result, as disclosed in FIG. 3, the amount of uric acid in the urine of the potassium oxonate-administered group was statistically significantly reduced, compared to the control group (potassium oxonate-administered group), 200 mg/kg of egg shell membrane administration group and 50 mg/kg of Benz according to the present invention. Urinary uric acid levels of Benzbromarone were significantly increased.

Example 3. Koyosan BUN (Blood Urea Nitrogen) and creatinine ( creatinine ) Content analysis

In order to induce hyperuricemia in an animal model, a solution of 0.5% sodium carboxymethylcellulose (CMC-Na, pH 5.0) containing 0.1M sodium acetate was added to a 7-week-old male SD-rat. Dissolved 150mg/kg of potassium oxonate was injected intraperitoneally. 1 hour after intraperitoneal injection of potassium oxonate, 200 mg/kg of egg shell powder and positive control 10 mg/kg of allopurinol and 50 mg/kg of Benzbromarone were added to 0.1% of polyoxyethylene sorbitane monooleate. ) Was suspended in a 0.01M phosphate buffered saline (PBS) buffer solution and orally administered for 5 days. Thereafter, in order to measure the content of BUN and creatinine in the blood, blood was collected 2 hours after the final oral administration and serum was separated.

As a result, the change in the content of BUN in blood was statistically significantly increased in the potassium oxonate-administered group compared to the normal group, and 200 mg/kg of egg shell powder according to the present invention and 10 mg of the positive control group /kg of allopurinol and 50mg/kg of Benzbromarone were statistically significantly decreased compared to the control group.

On the other hand, the change in the content of creatine is compared to the control group (potassium oxonate administration group) as shown in Figure 5, the 200mg / kg of the egg shell membrane administration group, 10mg / kg of allopurinol and 50mg / kg of Benzbromarone according to the present invention. The content of creatinine in blood was significantly reduced.

Claims (8)

Health functional food composition for the prevention or improvement of metabolic disorders related to hyperuricemia or hyperuricemia comprising the egg shell membrane as an active ingredient. The prevention of hyperuricemia or hyperuricemia-related metabolic disorder according to claim 1, wherein the hyperuricemia-related metabolic disorder is any one selected from acute or chronic gout, gouty redness, gouty arthritis, gouty nephrolithiasis, and gouty nephropathy. Or a health functional food composition for improvement. The health functional food composition for preventing or improving hyperuricemia or metabolic disorders related to hyperuricemia according to claim 1, wherein the egg shell membrane is an avian egg shell membrane. The method of claim 1, wherein the composition is prepared in any one formulation selected from powders, granules, pills, tablets, capsules, candy, syrup, and beverages for the prevention or improvement of metabolic disorders related to hyperuricemia or hyperuricemia. Health functional food composition. A pharmaceutical composition for the prevention or treatment of metabolic disorders related to hyperuricemia or hyperuricemia comprising the egg shell membrane as an active ingredient. The pharmaceutical composition for preventing or treating hyperuricemia or metabolic disorders related to hyperuricemia according to claim 5, further comprising a carrier, an excipient, or a diluent in addition to the active ingredient. [6] The pharmaceutical composition for preventing or treating hyperuricemia or metabolic disorders related to hyperuricemia according to claim 5, further comprising a urate-lowering agent in addition to the active ingredient. The method of claim 7, wherein the urate-lowering agent is at least one selected from xanthine oxidase inhibitors, uric acid excretion promoters, urate oxidase, urine alkalinizing agents, and fenofibrate. Pharmaceutical composition for prophylaxis or treatment.

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