KR20180037496A - Composition for preventing, improving or treating hyperuricemia or metabolic disorders associated with hyperuricemia comprising Dryopteris crassirhizpma extract as effective component - Google Patents
Composition for preventing, improving or treating hyperuricemia or metabolic disorders associated with hyperuricemia comprising Dryopteris crassirhizpma extract as effective component Download PDFInfo
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- KR20180037496A KR20180037496A KR1020160127732A KR20160127732A KR20180037496A KR 20180037496 A KR20180037496 A KR 20180037496A KR 1020160127732 A KR1020160127732 A KR 1020160127732A KR 20160127732 A KR20160127732 A KR 20160127732A KR 20180037496 A KR20180037496 A KR 20180037496A
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- Prior art keywords
- hyperlipidemia
- extract
- gouty
- metabolic disorders
- preventing
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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Abstract
The present invention relates to a composition for preventing, ameliorating or treating hyperlipidemia or hyperlipidemia-related metabolic disorders comprising an extract of a spectator as an active ingredient. The spectral extract of the present invention not only inhibits the activity of xanthine oxidase, Which is an effective ingredient derived from a natural product, and thus can be widely used in industries related to hyperlipidemia or hyperlipidemia-related metabolic disorders, because it is relatively easy to supply raw materials. In particular, it can be effectively used for preventing, ameliorating or treating gout or gouty arthritis.
Description
The present invention relates to a composition for preventing, ameliorating or treating hyperlipidemia or hyperlipidemia-related metabolic disorders containing an extract of a spectator as an active ingredient.
Hyperuricemia is defined by serum uric acid levels in men over 6.8 to 7.0 mg / dL or in women over 6 mg / dL. Hyperlipidemia and hyperlipidemia-related metabolic disorders (for example, 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 white people. Gout and hyperuricemia are also prevalent in China, Japan, Polynesia and sub-Saharan Africa. The incidence of gout between 1990 and 2010 has nearly doubled, and the number of domestic gout patients has increased by an average of 14% per year .
Metabolic disorders associated with hyperlipidemia include not only gout but also acute, single arthritic, painful seizures of inflammatory arthritis, urinary stone calculus, nephrolithiasis and gout, due to uric acid crystals, deposits of intraurethral crystalloid crystals, Includes nephropathy. Long-term nephrolithiasis and gouty nephropathy are known to increase the risk of kidney damage and renal failure. Among the metabolic disorders associated with hyperlipidemia, gout is caused by uric acid (uric acid in the blood, body fluids, and joint fluids in the form of urate salt) as the concentration of uric acid (the product of metabolism of the substance called purine, ) Crystals are deposited on cartilage, tendons and surrounding tissues of joints. This phenomenon causes inflammation of the joints, resulting in recurrent seizures accompanied by severe pain. Deformations and deformities of the joints occur when the gouty nodules (tophi) due to urate crystals are deposited. In addition to abnormalities of the joints, kidney disease (kidney stones) that cause kidney disease and kidney stones caused by uric acid may occur.
In addition, gout occurs through stages such as asymptomatic hyperuricemia, acute gouty arthritis, intermittent gout, and chronic nodular gout. In early asymptomatic hyperuricemia, the concentration of serum uric acid increased, but symptoms such as arthritic symptoms, gouty nodules, and uric acid keratosis were not observed. Acute gouty arthritis is a stage of gouty episodes or kidney acrosis that occurs after a period of at least 20 years of hyperuricemia. Acute episodes of acute episodes of painful arthritis are characterized by a joint It is invasive and has no systemic symptoms, but gradually invades the joints and accompanies the fever. Intermittent gout refers to a period of time without symptoms between gout attacks. Most of them experience a second seizure between 6 months and 2 years after the first seizure, . Chronic nodular gout appears to resemble other types of arthritis when it is in a period of chronic nodular ventilation past a ventilated intermittent device. There is progressive stiffness and constant pain in the joints of the affected area.
Gout is known to be a clear and successful treatment of the disease, but it is often accompanied by other diseases such as hypertension and chronic renal failure. Therefore, side effects of medication should be carefully considered, and lifestyle changes Patients' efforts are essential to improve prognosis in long-term treatment. Gout and hyperuricemia are not included in the diagnostic criteria for metabolic syndrome, which is a complex disorder with hypertension, hyperlipidemia, hyperglycemia, abdominal obesity, and clinical manifestations that increase the risk of adult diseases such as arteriosclerotic heart disease and type 2 diabetes The metabolic syndrome is thought to be closely related. In Korea, it was reported that 44% of patients with gout were accompanied by metabolic syndrome. Gout usually occurs in the form of acute monoarthritis, but may involve small joints or rarely joints. Non-steroidal anti-inflammatory drugs (NSAIDs), which are used in the treatment of acute gout, are known to inhibit the inflammatory response and are known to inhibit the activity and migration of leukocytes, ), Steroids are all drugs that can effectively treat gout attacks, and selective cyclooxygenase (COX-2) inhibitors are known to have the same effects as the existing non-steroidal anti-inflammatory drugs.
In addition, maintaining the serum uric acid concentration below the saturation level for a prolonged period of time can reduce the size of already existing ventilated nodules (tophi) as well as prevention of acute gouty arthritis. In the chronic phase of gout, uric acid is lowered in the blood, and the uric acid lowering agent is classified into xanthine oxidase (XO) inhibitor and uricosuric agent according to the mechanism. Allopurinol and febuxostat, which was recently developed as a new drug. Allopurinol is a xanthine oxidase (XO) inhibitor that can be effectively used regardless of the cause of hyperuricemia, but the most serious side effect of allopurinol is hypersensitivity syndrome, Eosinophilia, hepatitis, kidney failure, etc., are known to be at risk of death. Unlike xanthine oxidase inhibitor or allopurinol, febuxostat is also a non-purine selective blocker, which is metabolized mainly in the liver to form glucuronide. Most cases of gout are chronic, and even if there are no symptoms, treatment is done to lower the anti - inflammatory drug and uric acid concentration prophylactically. These preventive treatments should be used after the disease has been maintained for a period of time in a calm state, otherwise the ventilation will recur more severely. However, there is a lot of controversy about the proper period of the illness, and it is also difficult to prevent the acute onset of the gout, which is intermittently recurrent, and the gout is caused by natural products. Inhibition of the enzyme, an oxidase, is still insufficient.
Meanwhile, the crowd ( Dryopteris crassirhizpma ) grows in the shade of the mountain tree. Root stems are 8 ~ 10mm in diameter and they are oblique, 25cm long, with leaves. The petiole is 10 ~ 25cm long, much shorter than the leaf, and the scales are closely packed. Scales are basal, 10 ~ 25mm long, glossy, yellowish brown or blackish brown, with pointed ends and long ridges on the edges. The leaves are inverted and bell-shaped, and are deeply cracked twice. Leaf pieces are 20 ~ 30 pairs, with a bar-like shape of a line, without a bag, with a pointed end, and scaly scales on both sides. Leaf pieces in the middle part of the leaf blade are the largest, and the leaves are small in size and spaced apart at the bottom. The split pieces of the leaf sculpture are long elliptical, dull end, dull sawtooth on the edge, and leaf vein from the central vein are usually divided into Y-shaped. The sporophyll group ruptures in two lines near the central vein of the leaf blade of the upper part of the leaf blade, and the apical membrane is round kidney-shaped, with irregular edges and cracked irregularly. Edible young leaves. In one room, rootstock is used as a medicinal material. It removes parasites, has a fever and detoxification effect, and has a hemostatic effect. In both cases, the ingredients are extracted to make drugs such as cottonseed. They are distributed in Korea, Japan, Sakhalin, Kuril Islands, and northeast China.
Korean Patent No. 1486523 discloses a pharmaceutical composition or health functional food composition for prevention or treatment of thrombosis, which comprises an extract of a spectator or a fraction thereof as an active ingredient. Patent Publication No. 2015-0073261 discloses a pharmaceutical composition for preventing and treating degenerative brain diseases comprising an extract of a spectator as an active ingredient, and Korean Patent Laid-Open Publication No. 2016-0080654 discloses a mixture for diets containing an extract of a crowd. .
However, a composition for preventing, ameliorating, or treating hyperlipidemia or hyperlipidemia-related metabolic disorders containing the extract of the present invention as an active ingredient has not been disclosed.
The present invention provides a composition for preventing, ameliorating or treating hyperlipidemia or hyperlipidemia-related metabolic disorders comprising an extract of a spectator as an active ingredient, The present inventors have completed the present invention by confirming that the spectral extract inhibits the activity of xanthine oxidase and reduces the uric acid in the serum of the animal model.
In order to achieve the above object, the present invention provides a health functional food for preventing or ameliorating hyperlipidemia or hyperlipidemia-related metabolic disorders containing an extract of a spectator as an active ingredient.
In addition, the present invention provides a pharmaceutical composition for preventing or treating hyperlipidemia or hyperlipidemia-related metabolic disorders containing an extract of a spectator as an active ingredient.
The present invention relates to a composition for preventing, ameliorating or treating hyperlipidemia or hyperlipidemia-related metabolic disorders containing an extract of a spectator as an active ingredient, which is effective for inhibiting the activity of xanthine oxidase, , Hyperuricemia or hyperlipidemia-related metabolic disorders. In particular, it can be effectively used for preventing, ameliorating or treating gout or gouty arthritis.
FIG. 1 shows the result of confirming a reduction in the urinary output of serum after administering the spectral extract of the present invention to a normal SD-rat animal model. The normal group means the normal animal model group, and the 200 mg / kg of the audience means the animal model group to which 200 mg / kg of the spectral extract was administered to the normal animal model.
FIG. 2 shows the results of confirming the decrease in the urinary output in the serum after administering the spectral extract of the present invention to an animal model of SD-lact that induces hyperlipemia. The normal group represents the normal animal model group, and the hyperacidemic group refers to the animal model group that induced hyperlipidemia by administering 150 mg / kg of potassium oxonate.
The present invention relates to a health functional food for preventing or ameliorating hyperlipidemia or hyperlipidemia-related metabolic disorders containing an extract of a spectator as an active ingredient.
Preferably, the hyperlipidemia-related metabolic disorder is any one selected from acute or chronic gout, gouty redness, gouty arthritis, gouty nephrolithiasis, and gouty nephropathy, but the present invention is not limited thereto. The gustatory redness is a symptom of reddening due to inflammation due to gout.
Preferably, the above-mentioned tube extract is extracted using a lower alcohol of C 1 -C 4 , water or a mixture thereof as a solvent, more preferably ethanol is used as a solvent, and still more preferably 70% (v / v) of ethanol as a solvent, but the present invention is not limited thereto.
The health functional food for preventing or ameliorating hyperlipidemia or hyperlipidemia-related metabolic disorders containing the above-mentioned spectral extract as an active ingredient may be manufactured from any one selected from beverage, ring, tablet, capsule and acid, Food or food, and can be suitably prepared according to a conventional method.
Examples of foods to which the spectral extract of the present invention can be added include meat products, sausages, breads, chocolate, candies, snacks, confectionery, pizza, ramen noodles, other noodles, dairy products including ice- Tea, a drink, an alcoholic beverage, and a vitamin complex, and includes all health foods in a conventional sense.
The health functional foods include various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, colorants and enhancers (cheese, chocolate etc.), pectic acid and its salts, alkynic acid and its salts, , pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. It may also contain flesh for the production of natural fruit juices and vegetable drinks. These components may be used independently or in combination.
The health functional food of the present invention may contain various flavors or natural carbohydrates as an additional ingredient. The natural carbohydrates are sugar monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetening agent, natural sweetening agents such as tau Martin and stevia extract, synthetic sweetening agents such as saccharine and aspartame, and the like can be used.
In addition, the present invention relates to a pharmaceutical composition for preventing or treating hyperlipidemia or hyperlipidemia-related metabolic disorders containing an extract of a spectator as an active ingredient.
In the above pharmaceutical composition, the hyperlipidemia-related metabolic disorder is preferably, but not limited to, any one selected from acute or chronic gout, gouty redness, gouty arthritis, gouty nephrolithiasis and gouty nephropathy. The gustatory redness is a symptom of reddening due to inflammation due to gout.
In addition to the above-mentioned effective ingredients, the composition may further include an uric acid salt lowering agent. The preferred urate reducing agent is at least one selected from xanthine oxidase inhibitor, uricosuric agent, urate oxydase, urine alkalizing agent and phenobibrate And may further comprise, in addition to the above-mentioned spectral extract, a further pharmaceutically acceptable carrier, excipient or diluent.
The pharmaceutical composition of the present invention may be 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 formulations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be 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 sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like. Examples of suppositories include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
The composition of the present invention may be administered orally or parenterally, and it is preferable to select the intraperitoneal, rectal, rectal, intravenous, intramuscular, subcutaneous, intrauterine or intracerebral injection methods during parenteral administration.
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 will depend on the type of disease, severity, , Sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention can be administered as an individual therapeutic agent or in combination with other therapeutic agents, and can be administered sequentially or simultaneously with conventional therapeutic agents, and can be administered singly or in multiple doses. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art.
The dosage of the composition of the present invention may be varied depending on the patient's body weight, age, sex, health condition, diet, administration time, administration method, excretion rate, and severity of disease.
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 merely illustrative of the present invention and that the scope of the present invention is not limited thereto.
Example 1. Preparation of spectral ethanol extracts
70% of 15ℓ relative to 1kg of the crowd (v / v) was added to ethanol, and then extracted in 85 ℃ for 3 hours under reduced pressure to filter a liquid at 50 ℃ concentrated and dried to afford the 26.3 g spectators extract of (confirmation required) Respectively.
Example 2. Spectral Ethanol Extract Xanthine Oxidase ( Xanthine oxidase ) Inhibitory activity
The inhibitory activity of xanthine oxidase was analyzed using the ethanol extracts prepared in Example 1 of the present invention. The inhibitory activity of Xanthine oxidase was analyzed by the method of Sirpe and Della corte [Stirpe F, Della Corte E. 1969. The regulation of rat liver xanthine oxidase. J Biol Chem 244: 3855-3563].
0.1 ml of the ethanol extract of 500 占 퐂 / ml of the spectrophotometer prepared in Example 1 and 0.2 ml of the substrate solution in which 2 mM of xanthine had been dissolved were added to 0.6 ml of 0.1 M potassium phosphate buffer (pH 7.5) . 0.1 ml of Xanthine oxidase (0.2 U / ml) was added thereto, followed by reaction at 37 ° C for 5 minutes. After the reaction was stopped by adding 1 ml of 1N HCl, the uric acid produced in the reaction solution was added, Was measured at an absorbance of 292 nm. The inhibitory activity of xanthine oxidase on the ethanol extracts of the cells was expressed as percentage (%). As a result, it was confirmed that xanthine oxidase was inhibited by treatment with ethanol extracts from the cells (Table 1) .
Example 3. Normal SD- Lette Identification of the decrease in uric acid contained in the blood in animal models
The 200mg / kg spectral extract and the positive control 50mg / kg allophilin were suspended in 0.01M phosphate buffered saline (PBS) buffer containing 0.1% polyoxyethylene sorbitane monooleate, The animals were orally administered once to an SD-rat model.
After 2 hours of oral administration, blood was taken after anesthetizing with ethyl ether and the amount of uric acid was measured using uric acid assay kit (ab65344, abcam, USA).
As shown in Fig. 1, the results of the measurement of the urine output of the blood showed that the uric acid amount was decreased to about 1.0 mg / dl by the administration of the spectral extract and that the blood uric acid was decreased by about 50% Respectively.
Example 4. Reduced effect of uric acid contained in serum in hypercalcemic-induced animal model
To induce hyperuricemia in the SD-rat, which is an animal model inducing hypercalcemia, it was dissolved in a 0.5% sodium carboxymethylcellulose (CMC-Na, pH 5.0) solution containing 0.1 M sodium acetate And 150 mg / kg of potassium oxonate was intraperitoneally injected.
After 24 hours, urine samples (ab65344, abcam, USA) were used to urinate and the model animals with hyperuricemia induced were selected. To the selected model animals, 200 mg / kg of spectral extract and positive control 50 mg / kg of allophilin were dissolved in 0.01 M phosphate buffered saline buffer solution containing 0.1% polyoxyethylene sorbitane monooleate Solution for 3 days and fasted for 16 hours on the day before the autopsy. Two hours after the last oral administration, blood was taken after anesthetizing with ethyl ether, and the amount of urine acid was measured using a uric acid assay kit (ab65344, abcam, USA).
As shown in FIG. 2, the uric acid amount in the serum was increased to about 3.2 mg / dl by the administration of potassium oxonate. The extract of the present invention was administered at a dose of 200 mg / kg / day As a result, it was confirmed that the amount of uric acid in serum decreased by about 40.66%.
Claims (8)
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| PCT/KR2017/011041 WO2018066952A1 (en) | 2016-10-04 | 2017-09-29 | Composition comprising crassirhizomae rhizoma extract as active ingredient for preventing, alleviating, or treating hyperuricemia or hyperuricemia-related metabolic disorders |
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| KR101590842B1 (en) * | 2014-05-23 | 2016-02-01 | 한국과학기술연구원 | Aster glehni extracts, fractions or compounds isolated therefrom for the treatment or prevention of Hyperuricemia or Gout |
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