KR100492470B1 - Composition for treating and preventing gout - Google Patents

Abstract

The present invention relates to a new therapeutic agent and health supplement foods capable of treating and preventing gout, the gout treatment of the present invention comprising a purified fish oil, green tea extract, western lioness extract, kelp extract, sanjoin extract and ginkgo biloba extract as essential components and The prophylactic composition can be useful for the prevention and treatment of gout by suppressing the production of uric acid and facilitating excretion.

Description

Composition for the treatment and prevention of gout {COMPOSITION FOR TREATING AND PREVENTING GOUT}

The present invention is a composition comprising fish oil and herbal ingredients, and relates to a novel therapeutic and dietary supplement capable of treating and preventing gout.

Gout is a disease known as caesarean and luxury disease for a long time. Westerners say, "Oh! When I have the gout, I feel as if I was walking on my eyeball." ), And Asians have arthritis that complains of severe pain without distinguishing between East and West. Recently, the diagnosis of uric acid in the joint fluid through polarized light microscopy enables accurate diagnosis.

Gout is a metabolic disease in which crystals of uric acid, which are formed long-lived with high levels of uric acid in the blood, are deposited on various tissues and cause various symptoms. Determination of uric acid in patients with gout can be deposited on all organs, and can be divided into hyperuricemia, gouty arthritis, gout renal disease, and gout nephrolithiasis, depending on the stage of disease and the organs involved. However, gout is a well-controlled disease, because its mechanism and treatment are relatively well known.

Increased uric acid in the blood may be due to (1) excessive production of uric acid, or (2) due to abnormalities in the excretion process through the kidneys. However, a temporary higher than normal level of uric acid in the blood does not cause gout soon.The higher the level of uric acid in the blood, the easier it is to form crystals of uric acid and deposit in many tissues. Several triggers cause gout symptoms. Therefore, gout symptoms usually indicate abnormally high levels of uric acid in the blood from 10 to 20 years ago.

Gout is common in men between 40 and 50 years of age, but in recent years, as civilization develops and dietary conditions change, the age at which it occurs is decreasing. Women rarely develop before menopause, but women who are taking long-term immunosuppressants, long-term diuretics, or reduced renal function after organ transplantation are prone to gout at childbearing age. The frequency is about 7 men and 1 woman.

As for gout and hereditary factors, the occurrence of gout due to the lack of specific enzymes involved in uric acid metabolism is inherited depending on the sex chromosomes or autosomal, but most gout patients have high blood pressure or diabetes. It can occur in a family under the influence of various factors, such as how it is inherited. The incidence of familial outbreaks in all patients usually tends to be hereditary between 30 and 40%. Therefore, if one of the family members has higher than normal gout or blood uric acid, family members need to test for uric acid by blood test.

Indeed gout is more important than the accompanying disease, rather than itself. In other words, hypertension, hyperlipidemia, arteriosclerosis, diabetes mellitus accompany well, and obesity, heavy drinking, overeating occurs well. In addition, the cause of death of gout patients is more often caused by complications of such accompanying diseases, such as heart disease, cerebrovascular disorders than gout itself.

In order to explain the cause of the ventilation, it is necessary to first examine the production and discharge of uric acid. Our body is made up of numerous cells, and every cell has a nucleic acid that contains genetic information, and the nucleic acid is also a purine and pyrimidine body. All cells in the human body are destroyed at the end of their life, and the final product of the breakdown of purine in the nucleus is uric acid. Uric acid in the blood is largely produced by two supply pathways, one is exogenous uric acid derived from the purine body contained in the ingested food, and the other is intrinsic from cells destroyed in the patient's own body. Uric acid. Here, since the change in blood uric acid level due to food is not so large, the amount of uric acid naturally occurring in the body is more important for the maintenance of uric acid in the blood. Most of the uric acid produced by this process is excreted in the urine through a complex process in the kidneys. When uric acid is balanced, production of uric acid can maintain blood uric acid at normal levels. Blood uric acid levels in normal adult males are 7-8 mg / dl or less, females are 6 mg / dl or less, and women have lower levels than men. Although there is an individual difference in blood uric acid level, when it exceeds 8 mg, pain appears and there is a risk of causing vascular disorders of the heart, kidney, and brain, and when more than 10 mg, seizures occur. After menopause, men and women are almost the same, or the differences between men and women change to a very small extent.

Looking at the symptoms of gout, acute seizures can be mistaken for diseases such as osteomyelitis or infectious arthritis, because acute attacks usually cause sudden swollen joints, pain and edema, and a reddish tint. Symptoms are usually good at night, and most of them are painful enough to touch your fingers. Factors causing acute seizures may include drinking, surgery, bleeding, infection, taking some medications, treating cancer with radiation, overeating and overwork, and severe exercise or severe bruises. Almost all patients are characterized by the loss of joint symptoms on their own within a few days to ten days. In the early stages, the frequency of recurrences usually increases with time, and the higher the uric acid level in the blood, the higher the number of relapses. In about 10% of patients, severe fever develops and polyarthritis occurs in multiple joints at once.

(1) Acute gout (limb edema)

Gouty arthritis is a representative arthritis in which about 85% to 90% of the patients initially develop acute arthritis in one joint. It usually occurs primarily in the joints of the lower extremities such as the big toe, ankle and knee. In particular, the big toe is the most characteristic involvement of the joint because it involves more than 90% of patients with pregout. Long-term symptoms can involve joints in the upper limbs, such as elbows and fingers, and the synovial sac around the elbows (a pocket with slippery, sticky fluid that softens the joint's movement).

(2) chronic gout (arthritis)

After a long time without treatment of gouty arthritis, the crystals of uric acid form a lump, which is deposited on the subcutaneous tissue and takes the form of a hard bump. These tissues can occur anywhere in the body, including the ear wheels, and even gout nodules are found on the valves of the heart. If the nodules spread systemically, these nodules also exist in the joints, resulting in chronic joint symptoms, resulting in chronic joint pain, dyskinesia, and joint deformation, which makes it difficult to treat. It is desirable to start treatment.

Gout is the most common arthritis, but crystals of uric acid may deposit in the kidneys, resulting in acute or chronic renal impairment. Renal lesions are mostly chronic kidney lesions except when acute renal failure develops, and severe dysfunction of kidney function is rare enough for hemodialysis. In addition, there are many reasons for the excretion of uric acid through the urine can cause stones in the kidneys or urinary tract. The kidney and urinary stones are mostly calcium, but recently, uric acid-induced kidney stones are on the rise.

Koyosan (高 尿 酸) is very easy to control, so you only need to take the medicine properly, and be careful not to become obese. According to the statistics of death caused by gout, 1024 of 1600 deaths cause heart failure and renal failure, and the vascular disorders of the heart account for 60%. This high uric acid level is one of the causes of vascular disorders of the heart and brain, so removing one risk factor is a gout treatment.

As a gout treatment, in the case of acute gouty arthritis, early treatment is more effective, so the involvement joint is stabilized and anti-inflammatory drugs are administered promptly. There are usually three types, colchicine, nonsteroidal anti-inflammatory drugs, and steroids. Colchicine is commonly used in cases where the diagnosis of gout is unclear, and 0.6 mg is used up to 10 times an hour, until pain is relieved, or until side effects such as abdominal pain, diarrhea, nausea and vomiting appear. Nonsteroidal anti-inflammatory drugs are used when there are no complications and the diagnosis is clear, but peptic ulcers, renal dysfunction, and edema may worsen. Steroids are used for intraarticular injections or intramuscular injections in single arthritis.

Antihyperacid therapy is used for two or more episodes of acute gouty arthritis or chronic goutnoarthritis, aiming to maintain blood uric acid levels below 6.4 mg / dl. Antihyperacids include the uric acid production inhibitor "allopurinol (gyroic)" and "probeneside" to promote the excretion of uric acid. It should be noted that when using antihyperacids, acute arthritis may occur due to a sudden drop in uric acid. It should be prevented with colchicine or nonsteroidal anti-inflammatory drugs until blood uric acid levels are below normal or there is no acute onset for 3 to 6 months after the start of treatment.

The effect of food on blood uric acid during gout treatment is not so large that it is not necessary to be tied to a diet. For example, even a purine-free purine-free meal, blood uric acid can only drop about 1 mg / ㎗, and in fact, a meal without purine at all is difficult to continue for a long time. However, even if medication is continued, blood uric acid does not go down well, and if arthritis keeps recurring, or people who have arthritis immediately after overeating, or those with acute symptoms, limit the diet of group 3 with very high purine. It is good. According to the content of purine, food is divided into three groups as follows. When there are no symptoms, it is better to consume nucleic acid foods belonging to the three groups as appropriately. In addition, by increasing the intake of water to increase the amount of urine to about 2 ℓ is also effective in controlling uric acid and preventing urinary stones caused by uric acid to some extent. In addition to the general food, alcohol must be prohibited in principle, because alcohol increases the synthesis of uric acid in the blood and suppresses excretion in the urine, thereby increasing the incidence of acute attacks. Among alcoholic drinks, beer is no better than alcoholic drinks because of the more pronounced increase in uric acid because of the purinche contained in it.

Classification of foods according to the content of purine

(1) 1st group (0-15 mg): food which can be eaten

Eggs, cheese, milk, cereals (except oatmeal and whole grains), bread, most vegetables, fruits, sugar

(2) 2nd group (50-150 mg): food which can be eaten after recovery

Meat, poultry, fish, shellfish, beans, spinach, mushrooms, asparagus

(3) 3rd group (150-800 mg): food to be avoided

Internal organs (heart, liver, spleen, kidneys, tongue, brain, etc.), juicy, goose, sardines, herring, anchovies, mackerel, meju, yeast, bacon

On the other hand, patients with gout have some cautions besides medication to prevent intermittent acute attacks. For example, abstain from taboo foods such as alcohol and avoid overwork. In addition, diabetic, hypertension, obesity, hyperlipidemia, arteriosclerosis, which are frequently associated with gout, excessive weight, hyperlipidemia, which is a common problem, should be controlled with proper diet and exercise. Smoking is not related to gout itself, but it is a rule to stop smoking if you have any of the above conditions. Excessive exercise or lack of moisture can also encourage gout attacks.

That is, gout is a metabolic and chronic disease, so it is impossible to cure it once or twice. But if you continue your medications, it's easy to control the disease well enough to prevent it from happening again.

As discussed above, an imbalance in the production or excretion of uric acid in the human body may cause excessive uric acid concentrations in the blood and eventually cause gout, and in particular, intake of foods rich in nucleic acids may increase uric acid in the blood. have. Uric acid can be produced from xanthine by the enzyme xanthine oxidase, so administration of xanthine oxidase inhibitor allopurinol may inhibit the production of uric acid. It has severe side effects such as nephritis, allergies and gastrointestinal disorders. In addition, colchicine is also used, this also has side effects such as abdominal pain, diarrhea nausea, vomiting, and when using nonsteroidal anti-inflammatory drugs, there is a problem that peptic ulcer, kidney dysfunction, edema may worsen.

In the present invention, an object of the present invention is to provide a new therapeutic agent and dietary supplement that can treat and prevent gout without the side effects mentioned above.

The gout treatment and prevention composition of the present invention for achieving the above object, the purified fish oil, green tea extract, hawthorn extract, kelp extract, sanjoin extract and ginkgo leaf extract as essential components.

Here, the composition for gout treatment and prevention of the present invention, purified fish oil 60-80%, green tea extract powder 5-15%, Western Lioness extract powder 3-10%, kelp extract powder 2-6%, Sanzoin extract powder 1 It is preferable to use -5% and 1-5% of ginkgo biloba extract powder as essential components, 70% refined fish oil, 10% green tea extract powder, 6% western hawthorn extract powder, 4% kelp extract powder, 3% sanjoin extract powder And 3% of the ginkgo biloba extract powder as the essential component.

Here, the refined fish oil includes DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid), and green tea, hawthorn, kelp, sanjoin and ginkgo biloba extracts refer to their methanol extracts.

Refined fish oil (containing DHA & EPA) in the composition of the present invention enhances blood circulation to promote excretion of uric acid. In addition, herbal extracts of green tea, western hawthorn, kelp, sanjoin and ginkgo biloba extracts inhibit the xanthine oxidase involved in the production of uric acid, lowering the concentration of uric acid in the blood, and improving blood circulation to help excrete uric acid.

Specifically, green tea (綠茶) refers to tea made by using non-fermented tea leaves, and tea-plant ( Thea sinensis ) is an evergreen tree or shrub of the dicotyledonous plant-membranous tea tree. Tea contains tannic acid, caffeine, and amino acids. Tannin acid is associated with astringent taste, astringent and hemostatic effect, and caffeine is a bitter ingredient that stimulates nerves to promote blood circulation and diuretic effect. It is effective in recovery and amino acids are related to the sweetness of tea. Green tea, in particular, is known for its high levels of vitamin C (Doosan World White and EnCyber).

Craze oxycantha is produced in Europe, North Africa, and West Asia, and is a good cardiovascular agent for myocardial weakness caused by the elderly and acute infectious diseases. In addition, lowering peripheral resistance lowers blood pressure and is effective for the heart with hypertension, obesity, and early arteriosclerosis. This effect of western hawthorn is known to be due to the flavonoids (flavonoids) recently (published by the journal of modern biopharmaceuticals, herbal medicine research, Hakchangsa).

Laminaria is a genus of brown seaweed kelp, kelp, and carbohydrates such as carotene, xanthophylls, and chlorophyll. Contains a lot of amino acids, such as iodine, vitamin B2, glutamic acid. In particular, since there are many inorganic salts such as iodine, potassium, and calcium, it is good to eat kelp a little more often for the supply of inorganic salts, and the amino acid called laminin in kelp is known to lower blood pressure (Doosan World White and EnCyber). ).

Sanzoin (Zizyphi Spinosi Semen) is the seed of Zizyphus jujuba Miller, whose water-soluble fraction has a hypnotic effect, prolongs defensive conditional reflection, has a sustained lowering and calming effect on blood pressure. The saponin fraction of Sanjoin and the physiological activity of C-flavonoid are recognized, and it has been applied to sleep insomnia, anti-writhing behavior activity, sedative effect, insomnia, soothing, palpitation, etc. ).

In addition, the ginkgo biloba extract is a leaf extract of Ginkgo biloba Linn, and is known to be used in the treatment of brain improvement (nootropic), vascular insufficiency, and the like.

These herbal extracts, as found in the effect test example of the present invention, by inhibiting xanthine oxidase involved in the production of uric acid lowers the concentration of uric acid in the blood, and promotes blood circulation to help excretion of uric acid. Therefore, it may be useful in the prevention and treatment of gout included in the composition of the present invention together with purified fish oil (containing DHA & EPA) to enhance the blood circulation to promote the excretion of uric acid.

The composition of the present invention is prepared as follows.

First, extract powder of each herbal medicine is prepared. That is, green tea, wild lion, kelp, sanjoin, and ginkgo biloba each are powdered, 6-12 times the weight of each herbal powder is added to extract methanol for 20-25 to 23-25 hours, and the filtrate is concentrated under reduced pressure and dried. To extract powder. At this time, the amount of the dried herbal extract powder may vary depending on the ratio of the raw herbal medicine and the extract, extraction time, etc., but in general, green tea is about 9 ± 3 g with respect to 100 g of raw herbal medicine, and in case of western mountain lions, raw herbal medicine 100 About 14 ± 2 g for g, about 12 ± 3 g for 100 g of raw herbal medicine for kelp, about 13 ± 3 g for 100 g of raw herbal medicine for sanjoin, and about 100 g of raw herbal medicine for bank 10 ± 3 g are obtained.

Next, these herbal extract powders are mixed with other ingredients, such as 70% refined fish oil, 10% green tea extract powder, 6% hawthorn extract powder, 4% kelp extract powder, 3% sanjoin extract powder and 3% ginkgo leaf extract powder. The composition of the present invention is prepared by mixing in proportion, and adding appropriate amounts of various vitamin mixtures such as vitamin A, B1, B2, B6, B12, C, vitamin E, and egg yolk lecithin as necessary.

The composition of the present invention thus prepared may be mixed with conventional excipients as needed to prepare the respective formulations according to conventional powder, granule, capsule and tablet preparation methods.

The composition of the present invention can be administered orally by dividing the amount of 2-3g per day 1-3 times in adults.

Preferably, a capsule is prepared from a capsule containing 500 mg of the composition of the present invention per capsule, and in the case of an adult, two capsules are taken two to three times a day.

Hereinafter, the preparation method and the effect of the herbal composition of the present invention will be described in detail through Examples.

Preparation Example

Green tea, wild lion, kelp, sanjoin, and ginkgo biloba each were powdered, about 7 times the weight of each herbal powder was added to extract methanol for 23 to 24 hours, and the filtrate was vacuum dried to prepare extract powder of each herbal medicine. At this time, the amount of each herbal extract powder obtained was 8.5 g for 100 g of raw herbal medicine for green tea, 14.1 g for 100 g of raw herbal medicine for western mountain lions, 10.2 g for 100 g of raw herbal medicine for kelp, and sanjoin It was 13.5 g for 100 g of crude herbal medicine and 9.8 g for 100 g of crude herbal medicine.

Next, these herbal extract powders were mixed with refined fish oil and other ingredients according to the composition of Table 1 below, and then filled into capsules to prepare capsules having a content of 500 mg.

Component content(%) Refined fish oil (DHA 27%, EPA 5%) 70 Green Tea Extract Powder 10 Western Lioness Extract Powder 6 Kelp Extract Powder 4 Sanjoin Extract Powder 3 Ginkgo Leaf Extract Powder 3 Vitamin mixtures (vitamins A, B ₁ , B ₂ , B ₆ , B ₁₂ , C, etc.) 1.5 Egg yolk lecithin 1.5 Vitamin E 0.01

Effect Test Example

500 mg of the capsules and the raw herbal extract powders prepared in the above Preparation Example were used for the next test.

(1) Xanthin oxidase inhibition

Xanthine oxidase inhibition efficacy was measured at 295 nm using a spectrophotometer.

Xanthine solution (0.15 mM) was dissolved in xanthine (Sigma Co.) in a small amount of NaOH, adjusted to pH 7.5, and dissolved in 50 mM potassium phosphate buffer (xanthine oxidase solution). Final concentration: 0.2 U / mL).

The reaction solution comprises 0.25 ml (0.4 mg / ml in 50 mM potassium phosphate buffer, pH 7.5), 0.385 ml of 50 mM potassium phosphate buffer (pH 7.5), and 0.330 ml of xanthine solution, The final composition concentration was such that 100 μg of composition was included per ml of assay solution.

The reaction was started by adding 0.035 ml of xanthine oxidase solution to the reaction solution, and the absorbance (Absorbance, Ab) at 295 nm was measured after the reaction for 3 minutes at room temperature. Allopurinol at a concentration of 100 μg / ml was used as a standard inhibitor, and its inhibitory effect was measured as follows.

Inhibition (%) = (1-B / A) x 100

From here,

A is a change in Ab concentration in the absence of the composition (Ab with enzyme-Ab without enzyme),

B is Ab with enzyme-Ab without enzyme in the presence of the composition.

Table 2 shows the xanthine oxidase inhibitory effect of each herbal component in the composition of the present invention.

Herbal ingredient in the composition of the present invention control(%) Green Tea Extract Powder 92 Western Lioness Extract Powder 85 Kelp Extract Powder 68 Sanjoin Extract Powder 64 Ginkgo Leaf Extract Powder 78

As shown in Table 2, the herbal composition extracts of the present invention, green tea, hawthorn, kelp, sanjoin, ginkgo biloba, etc. effectively inhibit xanthine oxidase, and thus inhibit the production of uric acid. This effect is probably due to flavonoids, polyphenols, coumarins, or tannins in plant components. These compounds in plants are already well known as inhibitors of xanthine oxidase, and the compositions of the present invention in addition have the effect of clearing blood and inhibiting fat absorption.

(2) Measurement of uric acid in the blood

Since gout is a metabolic disease that occurs more frequently in men than in women, we tested five male patients with gout and five normal subjects. That is, the composition of the present invention is ingested three times a day (once a day for two capsules) for 5 days. Blood was collected, serum was obtained by centrifugation, and blood uric acid was analyzed by an Olympus AU600 analyzer.

The following table shows the changes in serum uric acid concentration (unit: mg / dl) according to the administration of the composition of the present invention, Table 3 is the change of uric acid concentration in gout patients and Table 4 is the change of uric acid concentration in normal people . In addition, Figure 1 is a graph showing the change in serum uric acid concentration according to administration of the composition of the present invention in gout patients and normal people.

Gout patient 0 days 1 day 3 days 6 days One 10.21 7.31 5.52 4.76 2 9.57 7.45 4.32 5.34 3 9.89 6.56 4.67 4.39 4 9.71 5.78 5.45 5.12 5 11.11 6.15 4.42 5.23 Average 10.10 6.65 4.88 4.97

Normal people 0 days 1 day 3 days 6 days One 4.31 3.45 3.12 3.76 2 6.34 5.32 4.37 4.64 3 5.67 4.58 3.67 4.72 4 3.81 3.39 3.44 3.12 5 5.34 4.15 3.42 4.23 Average 5.10 4.18 3.60 4.09

As shown in Table 3 above, the uric acid concentration before administration of the composition of the present invention in gout patients was 10.1 mg / dl, but decreased to 6.65 mg / dl after one day and further decreased to 4.88 mg / dl after three days. The uric acid concentration was slightly increased to 4.97 mg / dL as measured on day 5 of the dosing and on the last 6 days of the day. On the other hand, as shown in Table 4, the uric acid concentration was 5.10 mg / dL before administration of the composition of the present invention, but 4.18 mg / dL on day 1, 3.60 mg / dL after 3 days, and 6 days after 5 days of administration. At day 4.09 mg / dl. These results suggest that the composition of the present invention inhibits xanthine oxidase involved in uric acid production and eventually lowers blood concentration of uric acid.

On the other hand, unsaturated fatty acids DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) contained in the fish oil of the composition of the present invention is known as a substance that suppresses the formation of blood clots and helps blood circulation, thereby increasing the excretion of uric acid It is feed. Therefore, it can be seen that the present invention composition comprising fish oil and herbal extracts is very effective in the treatment and prevention of gout by being involved in the formation and excretion of uric acid in combination.

As described above, the composition of the present invention can be usefully used for the prevention and treatment of gout by inhibiting the production of uric acid and facilitating excretion.

1 is a graph showing the change in serum uric acid concentration according to the administration of the composition of the present invention in gout patients and normal people.

Claims (5)

A purified fish oil, green tea extract, hawthorn extract, kelp extract, sanjoin extract and ginkgo leaf extract as essential components, gout treatment and prevention composition. According to claim 1, 60 to 80% of purified fish oil, 5 to 15% of green tea extract powder, 3 to 10% of Western Lioness extract powder, 2 to 6% of kelp extract powder, 1 to 5% of sanjoin extract powder and 1 ginkgo leaf extract powder 1 A composition containing -5% as an essential component. The composition according to claim 1, wherein the composition comprises 70% purified fish oil, 10% green tea extract powder, 6% hawthorn extract powder, 4% kelp extract powder, 3% sanjoin extract powder and 3% ginkgo leaf extract powder. The composition of claim 1, wherein the purified fish oil comprises docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). The composition according to any one of claims 1 to 3, wherein the green tea, hawthorn, kelp, sanjoin and ginkgo biloba extracts are methanol extracts thereof.