KR102002298B1 - Compositions for preventing, ameliorating or treating hyperuricemia or metabolic disorders associated with hyperuricemia comprising herbal extracts - Google Patents

Abstract

The present invention relates to a composition for preventing, ameliorating or treating hyperlipidemia or hyperlipidemia-related metabolic disorders including herbal extracts, and more particularly, to a composition for preventing, ameliorating or treating hyperlipidemia or hyperlipidemia- Or a pharmaceutical composition for preventing or treating hyperlipidemia-related metabolic disorders and / or a health functional food composition for prevention or improvement. The herbal medicine extract combination of the present invention is excellent in the effect of suppressing edema, reducing inflammatory cytokine and decreasing blood uric acid concentration in a uric acid crystal (MSU) -induced gout animal model, thus preventing or improving hyperlipidemia or hyperlipidemia-related metabolic disorders Or can be used therapeutically.

Description

[0001] The present invention relates to a composition for preventing, ameliorating or treating hyperlipemia or metabolic disorders associated with hyperlipemia associated herbal extracts,

The present invention relates to a composition for preventing, ameliorating or treating hyperlipidemia or hyperlipidemia-related metabolic disorders including herbal extracts, and more particularly, to a composition for preventing, ameliorating or treating hyperlipidemia or hyperlipidemia- Or a pharmaceutical composition for preventing or treating hyperlipidemia-related metabolic disorders and / or a health functional food composition for prevention or improvement. The herbal medicine extract combination of the present invention is excellent in the effect of suppressing edema, reducing inflammatory cytokine and decreasing blood uric acid concentration in a uric acid crystal (MSU) -induced gout animal model, thus preventing or improving hyperlipidemia or hyperlipidemia-related metabolic disorders Or can be used therapeutically.

Hyperuricemia refers to an abnormally increased concentration of uric acid in the blood. This occurs when the concentration of urate crystals in the serum exceeds the limited solubility limit. 37, the uric acid saturation of plasma is about 7 mg / dL, and when it exceeds this concentration, it becomes physico-chemically supersaturated. The serum uric acid concentration is known to be relatively high when the serum uric acid concentration is higher than the normal serum uric acid concentration of normal persons by more than +2 standard deviation. In most epidemiological studies, the upper limit of the male is 6.8 to 7.0 mg / dL, to be. For this reason, the actual upper limit level of hyperlipidemia is defined as 7.0 mg / dL or more.

Hyperlipidemia and hyperlipidemia-related metabolic disorders occur in 3 to 5 million people in the United States, and African Americans are twice as likely to have hyperaemia-related metabolic disorders than white people. Hyperuricemia is also prevalent in China, Japan, Polynesia and sub-Saharan Africa.

Therapeutic agents for hyperuricemia include 1) xanthine oxidase inhibitors (alopurinol, bevacostat), 2) uric acid excretion promoters (sulfinpyrazone, benzbromarone, provenecid), 3) urate oxydase (NSAIDs), such as NSAIDs, have been used for the treatment of hyperlipidemia-related metabolic disorders, including: 1) nonsteroidal antiinflammatory drugs (NSAIDs); 2) corticosteroids, and 3) anti-inflammatory drugs (colchicine). These treatments function to lower the uric acid level in the blood, and by using therapeutic agents, restoring the blood uric acid level to the normal range can prevent other metabolic disorders related to hyperuricemia.

However, many of the therapeutic agents used in hyperlipidemia or hyperlipidemia-related metabolic disorders are known to have various side effects. For example, xanthine oxidase inhibitors such as allofurinol are associated with hypersensitivity vasculitis, Stevens-Johnson syndrome, desquamative dermatitis, aplastic anemia and hepatic dysfunction. Urinary excretion enhancers, such as probenecid and benzbromarone, have side effects such as gastrointestinal disorders, urinary tract necrosis, and fulminant hepatic insufficiency in patients with idiopathic hypertension. In addition, long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) can lead to side effects, including ulcerative perforation and upper gastrointestinal bleeding.

Therefore, the development of novel agents for the prevention and treatment of hyperlipidemia and hyperlipidemia-related metabolic disorders is still required, and studies using natural products are underway. Korean Patent Laid-Open Publication No. 10-2015-0135037 discloses an extract of Mulberry japonica extract effective for hyperuricemia or gout, fractions thereof and active compounds isolated therefrom, and Korean Patent Publication No. 10-2010-0117979 discloses a black onion extract The present invention provides a composition for preventing or treating gout or hyperlipidemia comprising an effective ingredient of the present invention. However, the therapeutic effect on hyperlipidemia or hyperlipidemia-related metabolic disorders of the extracts, habits, dermis, licorice, health and / There is no bar.

The present inventors have conducted studies to develop a therapeutic agent for hyperlipidemia or hyperlipidemia-related metabolic disorders, which are safe for the human body and have no side effects by combining various herbal medicines, inhibit swelling, suppression of edema of health and / or jujube extract, The effect of reducing the inflammatory cytokine and the effect of decreasing the uric acid concentration in the blood were confirmed and the present invention was completed.

Accordingly, it is an object of the present invention to provide a composition for preventing, ameliorating or treating hyperlipidemia or hyperlipidemia-related metabolic disorders using the extract, bark, dermis, licorice and health extract.

In order to achieve the above object, the present invention provides a method for treating acute gouty arthritis (GSS) caused by hyperuricemia, gout, deposition of urate crystals in the joints, deposition of urate crystals, , Urinary incontinence, urinary incontinence, urinary incontinence, urinary incontinence, urinary incontinence, urinary incontinence, urinary incontinence, urinary incontinence, urinary incontinence, urinary incontinence, urinary incontinence, urinary incontinence,

According to a preferred embodiment of the present invention, the composition may contain the extracts of Creation, Lilac, Dermatophyte, Licorice and Health Extract in a weight ratio of 5-10: 1 ~ 7: 3 ~ 8: 1 ~ 4: 2-8 .

According to another preferred embodiment of the present invention, the composition may further comprise jujube extract.

According to another preferred embodiment of the present invention, the composition comprises 5 to 10: 1 to 7: 3 to 8: 1 to 4: 2 to 8: 2 to 10: 1, 6 by weight.

The composition comprising the active ingredient as the active ingredient, the composition of the present invention, the composition of the present invention, the composition of the present invention, the composition of the present invention, the composition of the dermis, the dermis, the licorice and the health extract, , Inflammatory cytokine expression suppressing effect and pain suppressing effect, and exhibits excellent blood uric acid reducing effect in a low animal animal model, so as to prevent, ameliorate or treat hyperuricemia or hyperuricemia related metabolic disorders, quasi-drugs and health function Food and the like.

Brief Description of the Drawings Figure 1 is a schematic representation of the gouty arthritis mouse model and drug treatment schedule used in the present invention.
FIG. 2 shows the results of a mouse model of MSU-induced gouty arthritis mice, in which 300 mg / kg of water extracts were individually administered or in combination with water extracts of Chinese cabbage, Chinese cabbage, dermis, licorice, The composition (F055-1) of the herbal medicine water extract (F055-1) mixed with the herbal medicine extract (F055) and the herbal medicine extract obtained by mixing the herbal medicine, extract, dermis, licorice and health were respectively administered at a concentration of 300 mg / ( P <0.0001 vs. con mice, * p <0.05, ** p <0.01, *** p <0.001 vs. MSU-induced mice).
FIG. 3 is a graph showing the effect of a water extract of 300 mg / kg on the MSU-induced gouty arthritis mouse model alone, herbal, dermis, licorice and health water extracts, (F055-1) was administered at a concentration of 150 or 300 mg / kg, and folds of the mouse sole of each group were folded on the basis of Con group (#### p <0.0001 vs. con mice , * p < 0.05, vs. MSU-induced mice).
FIG. 4 shows the results of a mouse model of an MSU-induced gouty arthritis mouse in which 300 mg / kg of water extracts of each of the extracts, creams, dermis, licorice, health and jujube were administered alone or in combination, The composition of herbal medicine water extract (F055-1), which is a mixture of herbal medicine extract (F055) and a herbal medicine extract (F055-1), which is a mixture of herbaceous fungi, dermis, licorice and health, was administered at a concentration of 300 mg / kg, measuring the expression level of the protein -1β then the IL-1β protein expression level of vehicle control group (MSU) to the 100% reference shows the IL-1β protein expression levels in each treatment group, expressed as a percentage (* p <0.05 vs. MSU-induced mice).
FIG. 5 is a graph showing the effect of the extract of herbal medicine on the MSU-induced gouty arthritis mouse model alone or in combination with the production of 300 mg / kg of the herb extract, herb extract, dermis, licorice extract and health extract, after the composition (F055-1) was administered at 150 or 300 mg / kg concentration was collected from the mouse tissue shows a comparison graph by measuring the expression level of IL-1β protein (** p <0.01, vs. MSU- Induced mice).
FIG. 6 shows the composition of herbal medicine ethanol extract (F055E) and herbal medicine extract obtained by mixing the herb extract, herb, dermis, licorice and health in a MSU-induced gouty arthritic mouse model (* P < 0.05, ** p < 0.05), respectively, after administration of the composition (F055E-1) at a concentration of 300 mg / kg and a solvent control (MSU) 0.01, **** p < 0.0001 vs. MSU-induced mouse)
FIG. 7 shows the composition of herbal medicine ethanol extract (F055E) and herbal medicine extract obtained by mixing the herbaceous, flax, dermis, licorice and health compositions of herbal medicine ethanol extracts mixed with MSU-induced gouty arthritis mouse model, (# P < 0.05 vs. Con Mice) (F055E-1) at a concentration of 300 mg / kg, , ** p < 0.01 vs. MSU-induced mice)
8 shows a composition (F055E) of a herbal medicine ethanol extract obtained by mixing a herbicide, a dandelion, a licorice, a healthy and a jujube in a model of hyperuricemia and a composition of a herbal medicine ethanol extract obtained by mixing the herb, -1) at a dose of 400 mg / kg, respectively.

As described above, there is a continuing need for a therapeutic agent for hyperlipidemia and its associated metabolic disorders, which is safe for human body and has no side effects. Accordingly, various herbal medicine extracts with high human safety are used to treat hyperlipidemia and related metabolic disorders An attempt has been made to develop a high- The present inventors have sought a solution to the above-mentioned problem by providing a mixed herbal medicine extract using Creation, Lychee, Dermis, Licorice, Health and / or Jujube Extract. The composition comprising the active ingredient as the active ingredient, the composition of the present invention, the composition of the present invention, the composition of the present invention, the composition of the present invention, the composition of the dermis, the dermis, the licorice and the health extract, , Inflammatory cytokine expression suppressing effect and pain suppressing effect, and exhibits excellent blood uric acid reducing effect in a low animal animal model, so as to prevent, ameliorate or treat hyperuricemia or hyperuricemia related metabolic disorders, quasi-drugs and health function Food and the like.

The terms used in the present invention are defined as follows.

The term &quot; pharmaceutical composition &quot; is intended to encompass a generic herbal extract comprising the extract of the present invention, a mixed herbal extract comprising the extract, a dermis, a licorice and a health extract or a mixed herbal extract comprising the extract, &Lt; / RTI &gt; diluent or carrier.

The term &quot; carrier &quot; is defined as a compound that facilitates the addition of a compound into a cell or tissue. For example, dimethylsulfoxide (DMSO) is a commonly used carrier that facilitates the introduction of many organic compounds into cells or tissues of an organism.

The term &quot; diluent &quot; is defined as a compound that not only stabilizes the biologically active form of the compound of interest, but also dilutes in water to which the compound is dissolved. Salts dissolved in buffer solutions are used as diluents in the art. A commonly used buffer solution is phosphate buffered saline, since it mimics the salt state of the human solution. Since buffer salts can control the pH of the solution at low concentrations, buffer diluents rarely modify the biological activity of the compounds.

The term &quot; treatment &quot; means an approach to obtaining beneficial or desired clinical results. For purposes of the present invention, beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, reduction in the extent of disease, stabilization (i.e., not worsening) of the disease state, (Either partially or totally), detectable or undetected, whether or not an improvement or temporary relief or reduction Also, &quot; treatment &quot; may mean increasing the survival rate compared to the expected survival rate when not receiving treatment. &Quot; Treatment &quot; refers to both therapeutic treatment and prophylactic or preventative measures. Such treatments include treatments required for disorders that have already occurred as well as disorders to be prevented. "Alleviating" a disease may result in a reduction in the extent of the disease state and / or undesirable clinical symptoms and / or a slower or longer time course of the progression, It means to lose.

All technical terms used in the present invention are used in the sense that they are generally understood by those of ordinary skill in the relevant field of the present invention unless otherwise defined. Also, preferred methods or samples are described in this specification, but similar or equivalent ones are also included in the scope of the present invention.

Hereinafter, the present invention will be described in more detail.

The present invention provides a pharmaceutical composition for the prophylaxis or treatment of at least one disease selected from the group consisting of hyperuricacidemia and related metabolic disorders including Creation, Glucose, Dermis, Licorice and Healthy Extracts as active ingredients.

Creation (蒼朮) is a plant of Asteraceae, Atractylodes koreana Kitam. and sparrow A. japonica Koidz. And dried roots of the same plant, the taste is very high and the nature is warm. It acts on the nerves (脾 经), the stomach (胃 经), menopause (肺 经), and the colonoscope (肠 经), eliminating the ux (濕 邪), strengthening the spleen, perspiration, And brightens the eyes. In pharmacological experiments, diuretic, hematopoietic stimulation, and stomach action have been found.

Magnolia and Magnolia officinalis Rehd. It dried the roots and roots of et Wils. The taste is spicy and the quality is warm. It acts on the nerves (脾 经), the stomach (胃 经). It promotes circulation of the stomach, heals the stomach of the stomach, warms the stomach, removes the stomach, and removes the stomach. It has been shown that pharmacological experiments show antimicrobial activity and weak diuretic action. It is caused by a cold swallowing of the 脾 胃 (寒 濕 邪), and it is full of digestive disorder, vomiting, diarrhea, gastroenteritis, stomach cramps, coughing and breathing, bronchitis and bronchial asthma.

Dandelion (陳皮) is the mature peel of citrus (Citrus unshiu Markovich) or related plants in Korea. In Japan, Citrus unshiu Markovich (Citrus reticulata Blanco: 柑) is used as a dermis and Citrus tachibana (Makino Tanaka: 橘 柑) is used as a citrus peel. Citrus reticulata Blanco : 柑) and its cultivar varieties as dermis. It has a peculiar odor, is slightly irritating, it is spicy and spicy, and its quality is warm. Pharmacological action has been reported to cause the digestive tract stimulation, digestion promotion, geomorphic, anti-ulcer, antidiarrheal secretion, hypertension, elevated blood pressure, antiallergic, bile secretion promotion, uterine smooth muscle suppression,

Liquorice is licorice, licorice licorice belonging to the bean family, roots of the manchurian licorice and its plants, and liquiritigenin, glucose, mannitol, malic acid, l-asparagine, There are pharmacological effects such as viewing (补气) and detoxification (.) As the main ingredients. It is the main ingredient of detoxification, and the licorice is used to stimulate the nervousness as a symptom of relaxation and adjustment.

Health (生.) Is a perennial plant with ginger root, ginger, ginger, and is used as a medicinal plant in dried herbs. It treats chills, fever, headache, vomiting, seawater and sputum caused by cold. It is also effective in abdominal pain and diarrhea caused by food poisoning. Pharmacological action to promote gastric secretion, digestive power, cardiac excitement, blood circulation promotion, and bacillary action have been reported.

The produce, buckwheat, dermis, licorice, and health used in the present invention may be purchased commercially, sold or cultivated directly in nature.

In the composition of the present invention, the hyperlipidemia and hyperlipidemia-related metabolic disorders are caused when the uric acid is higher than the normal level and the ability of the kidney to excrete the uric acid is decreased, so that extra uric acid remains in the blood and the uric acid level in the blood increases Disease or disease.

Specifically, the hyperlipidemia-related metabolic disorders include acute arthritic arthritis, arthritic arthritis, painful seizures of inflammatory arthritis, urinary incontinence, urinary incontinence due to gout, uric acid crystals, deposition of urate crystals, Sickle cell disease and gouty nephropathy. Long-term nephrolithiasis and gouty nephropathy are known to increase the risk of kidney damage and renal failure.

The gout is usually a medical condition characterized by a recurrent seizure of acute inflammatory arthritis and is common in the mid-phalangeal joints of the base of the big toe. In addition, gout is caused by blood uric acid crystallized and deposited in the joints, tendons and surrounding tissues, and may be present as gout, kidney stones, or urate nephropathy.

In one embodiment of the present invention, the extracts were prepared after mixing the extracts, horseradish, dermis, licorice and health.

The extract of the present invention is preferably extracted with water, C ₁ to C ₄ lower alcohols or a mixture thereof, and the lower alcohol is preferably ethanol, methanol or butanol.

The extract is preferably, but not exclusively, prepared by a process comprising the steps of:

1) Extracting, extracting, extracting from the dermis, licorice, or health by adding an extraction solvent;

2) filtering the extract of step 1); And

3) Concentrating the filtered extract of step 2) under reduced pressure and drying.

In the above method, the extraction method of step 1) may be a conventional method in the art such as filtration, hot water extraction, immersion extraction, reflux cooling extraction, and ultrasonic extraction.

In the above method, it is preferable to use a vacuum decompression concentrator or a vacuum rotary evaporator for the decompression concentration in step 3), but it is not limited thereto. The drying is preferably performed under reduced pressure, vacuum drying, boiling, spray drying or freeze drying, but is not limited thereto.

The above-described creams, dandruff, licorice and health extracts may be mixed in a specific weight ratio to achieve optimal effects for treating hyperuricemia or related metabolic disorders. For example, the extract may be mixed at a weight ratio of 5 to 10: 1 to 7: 3 to 8: 1 to 4: 2 to 8, more preferably 6 to 8 : 2.5 to 5: 4 to 7: 1.5 to 3.5: 2.5 to 5.5. When the mixing ratio is out of the above range, the synergistic effect is decreased and the optimum activity can not be exhibited. In one embodiment of the present invention, the extracts were prepared in a weight ratio of 7.5: 3.75: 5.25: 2.25: 3.75.

The pharmaceutical composition of the present invention may further comprise a jujube extract in addition to the extracts, creams, dermis, licorice and health extracts.

The jujube is the jujube tree Zizyphus There is JuJuba Miller. inermis Rehder or Bojang Jujube Trees Zizyphus jujuba Miller var. hoonensis TB Lee (ripe berries and Rhamnaceae), ripe fruit, used in diuretics, strengths and emollients.

The jujube used in the present invention may be purchased commercially, or may be directly harvested or cultivated in nature, and jujube extract may be prepared by the above-described production method.

In the pharmaceutical composition of the present invention, when the jujube extract is added, the content of the extract is from 5 to 10: 1 to 7: 3 to 8: 1 to 4: 2 to 8: 2 to 5: 6, and more preferably 6: 8: 2.5 to 5: 4 to 7: 1.5 to 3.5: 2.5 to 5.5: 2.5 to 5, and the weight ratio When mixed, the synergistic effect is reduced and the optimum activity can not be exhibited. In one embodiment of the present invention, the extracts were used in a weight ratio of 7.5: 3.75: 5.25: 2.25: 4: 3.75.

As shown in FIG. 2, in the case of the MSU-induced gouty arthritic animal model, the effect of suppressing edema by the single water extract was excellent in the licorice water extract and the jujube water extract, and the composition of the mixed herbal medicine water extract was F055-1 Respectively. Despite the absence of jujube water extract which showed superior edema suppression effect in single water extract, it was unexpectedly confirmed that F055-1 was superior to F055 in edema suppression effect. As shown in FIG. 3, no significant swelling inhibition effect was observed in the experimental group administered with F055-1 at a concentration of 150 mg / kg, but the positive control group treated with colchicine (Col ) Than the control group.

In addition, as shown in FIG. 4, in the MSU-induced gouty arthritic animal model, the inhibitory effect of IL-1β protein on the expression of IL-1β by the single water extract was superior to that of jujube water extract (71.80%) and produced extract (74.62% The composition of herbal medicine water extract was more excellent than F055 (40.01%) than F055 (69.21%) as well as the edema suppression effect. Despite the absence of the jujube extract which showed the best inhibitory effect of IL-1β protein in the single water extract, it was confirmed that the inhibitory effect of F055-1 on IL-1β protein expression was superior to that of F055. In the case of the inhibitory effect of IL-1β protein expression, F055-1 showed a significant inhibitory effect even at a concentration of 150 mg / kg (FIG. 5).

In addition, the present inventors have found that a herbal medicine ethanol composition (F055E) comprising an MSU-induced gouty arthritic animal model and a mixture of herbaceous, flax, dermis, licorice, health and jujube extracts and a herbal medicine Ethanol composition (F055E-1) was confirmed to suppress the edema and the pain-suppressing effect according to the weight-bearing ratio. As a result, as shown in FIG. 6, F055E-1 (82.2%) showed a better swelling suppression effect than F055E (92.7%), and the MSU induction weight- 10%, but in the F055E-treated group, the weight-bearing ratio was increased to 45.6%, and in the F055E-1-treated group, the weight-bearing ratio was increased to the normal level.

In addition, as shown in Fig. 8, when F055E and F055E-1 were administered to an animal model in which hyperlipidemia was induced, the blood urine output decreased by 25.58% and 25.45%, respectively, compared with the group administered with potassium oxonate (PO) Effect.

The pharmaceutical compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.

The pharmaceutical composition according to the present invention can be formulated in the form of oral, granule, tablet, capsule, suspension, emulsion, syrup, aerosol or the like oral preparation, external preparation, suppository and sterilized injection solution according to a conventional method Can be used.

Examples of carriers, excipients and diluents that may be contained in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin , Calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

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 at least one excipient such as starch, calcium carbonate, sucrose or lactose , Gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included .

Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount.

The term "pharmaceutically effective amount " as used herein 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 species and severity, age, sex, The activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And can be administered singly or multiply.

The composition can be administered to mammals such as rats, mice, livestock, humans, and the like in a variety of routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection.

The present invention also provides a health functional food composition for preventing or ameliorating at least one disease selected from the group consisting of hyperuricacidemia and related metabolic disorders including Creation, Glucose, Dermis, Licorice and Health Extract as an active ingredient.

The health functional food composition may further comprise a jujube extract.

The above description of the above-mentioned health functional food composition, which is made with respect to the bark, dandelion, licorice, health and jujube extracts, is the same as that described above, so that description thereof will be omitted in order to avoid the excessive complexity of the present specification.

Likewise, the description of hyperlipidemia and its associated metabolic disorders in the health functional food composition is the same as described above, so that the description thereof is omitted in order to avoid the excessive complexity of the present specification according to the overlapping description.

In the present invention, the term &quot; health functional food &quot; refers to foods manufactured and processed using raw materials or ingredients having useful functions in accordance with Law No. 6727 on Health Functional Foods. Or to obtain a beneficial effect in health use such as physiological action.

The health functional foods of the present invention may contain conventional food additives and, unless otherwise specified, whether or not they are suitable as food additives are classified according to the General Rules for Food Additives approved by the Food and Drug Administration, Standards and standards.

Examples of the items listed in the above-mentioned "food additives" include chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; Natural additives such as persimmon extract, licorice extract, crystalline cellulose, high color pigment and guar gum; L-glutamic acid sodium preparations, noodle-added alkalis, preservative preparations, tar coloring preparations and the like.

The health functional food composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient as well as ordinary food compositions.

Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. The above-described flavors can be advantageously used as natural flavorings (tau martin), stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.).

The health functional food composition of the present invention can be formulated in the same manner as the above pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, meat, chocolates, foods, confectionery, pizza, ram noodles, other noodles, gums, candy, ice cream, alcoholic beverages, vitamin complexes, .

For example, the health functional food in the form of tablets may be prepared by granulating a mixture obtained by mixing the active ingredient of the present invention with an excipient, a binder, a disintegrant and other additives, granulating the mixture in a conventional manner, The mixture can be directly compression molded. In addition, the health functional food of the tablet form may contain a mating agent or the like if necessary.

The hard capsule of the capsule type health functional food can be prepared by filling a normal hard capsule with a mixture of an extract of the present invention and an additive such as an excipient. The soft capsule contains the active ingredient as an excipient such as an excipient, And filling the mixed mixture into a capsule base such as gelatin. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative and the like, if necessary.

The ring-shaped health functional food can be prepared by molding a mixture of a mixed herbal medicine extract, an active ingredient of the present invention, an excipient, a binder, a disintegrant, and the like by a conventionally known method and, if necessary, Or it may be coated with a material such as starch, talc.

The granular health functional food may be prepared by granulating a mixed herbal medicine extract, an active ingredient of the present invention, excipient, binder, disintegrant, etc., into granules by a known method, and if necessary, adding a flavoring agent, And the like.

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 examples are for illustrative purposes only and that the scope of the present invention is not construed as being limited by these examples.

Preparation of mixed herbal extracts

1-1. Preparation of F055-1 Composition

After grinding, 30 g, 15 g of ginger, 21 g of dermis, 9 g of licorice and 15 g of health were weighed into an extractor, and 1.5 L of distilled water was added to the extractor for 3 hours And extracted. The extracts were filtered using filter paper and then lyophilized for 4 days using a freeze dryer.

One- 2.F055  Preparation of composition

Weighing 30 g, 15 g, 15 g dermis, 21 g dermis, 9 g licorice, 15 g health, and 15 g jujube were weighed and added to the extractor, and then 1.5 L of distilled water And extracted for 3 hours. The extracts were filtered using filter paper and then lyophilized for 4 days using a freeze dryer.

1-3. F055E -1 composition

After the crushing, 30 g, 30 g, 30 g of ethanol, 15 g of dough, 21 g of dermis, 9 g of licorice and 15 g of health were weighed, Lt; / RTI &gt; The extracts were filtered using filter paper and then lyophilized for 4 days using a freeze dryer.

One- 4.F055E  Preparation of composition

After grinding, weighing 30 g, 15 g, 15 g dermis, 21 g dermis, 9 g licorice, 15 g health, and 15 g jujube were weighed and placed in an extractor, and then 30% ethanol 1.5 L was added and the mixture was extracted for 3 hours. The extracts were filtered using filter paper and then lyophilized for 4 days using a freeze dryer.

Evaluation of F055-1 and F055 Efficacy in Gouty Arthritis Animal Model

2-1. Identification of edema inhibition effect

In order to confirm the therapeutic effect of the mixed herbal medicine extract of the present invention on gouty arthritis, a maleate crystal (MSU) -induced gouty arthritis mouse model was used.

Specifically, the F055-1 composition and the F055 composition prepared in Examples 1-1 and 1-2 were orally administered to 7 week old C57 / BL6 mice (Orient Bio), respectively. After 1 hour, 4 mg of urate MSUs were suspended in 50 μl of PBS containing 2.5% Tween 80 and injected into the right foot tissue to induce gouty arthritis. After the experimental drug was administered once a day for 4 days to the mouse model, the edema was mitigated by measuring the sole thickness using a vernier scale on the fifth day (Fig. 1).

The effects of 300 mg / kg of the extracts obtained from the same extraction methods as in Examples 1-1 and 1-2, respectively, were separately administered to each of the extracts, (F055-1) or a composition of water extract (F055-1) containing 300 mg / kg of a composition of herbal medicine extract (F055) mixed with dermis, licorice, Was administered at a dose of 150 or 300 mg / kg to confirm the synergistic effect.

The normal control group (Con) was administered 0.25% of carboxymethyl cellulose (CMC) to MSU-untreated mice and the solvent control group (MSU) was administered 0.25% of CMC to MSU-induced gouty arthritis mice. The control group (Col) administered colchicine to mice that induced gouty arthritis with MSU.

The foot thickness of each treated group was measured based on the thickness of the sole of the normal control (Con), and the results are shown in Fig. 2 as folds. As shown in FIG. 2, when the single extract and mixed herbal extracts were administered at a concentration of 300 mg / kg, the edible extract and the jujube extract were superior to the F055, -1 was better. Despite the fact that the jujube extract showed no superior edema inhibitory effect in the single extract, the suppression effect of F055-1 on swelling was superior to that of F055, unexpectedly.

In addition, as shown in FIG. 3, no significant swelling suppression effect was observed in the experimental group administered with F055-1 at a concentration of 150 mg / kg, but the positive control group treated with colchicine at the concentration of 150 mg / (Col).

2-2. Identification of the inhibitory effect of inflammatory cytokine expression

The mouse model of Example 2-1 was autopsied on day 5, foot tissue was collected, immersed in RIPA buffer solution, and the tissue was disrupted to measure the expression level of IL-1β protein, an inflammatory indicator, in the supernatant by ELISA.

The level of IL-1 beta protein expression in each treatment group was shown in percentage as a percentage based on 100% of the IL-1 beta protein expression level of the solvent control (MSU). The lower the%, the better the IL-1 beta protein expression inhibitory effect .

As shown in FIG. 4, the inhibitory effect of IL-1β on the expression of IL-1β by the single extract was higher than that of jujube extract (71.80%) and produced extract (74.62%), ), And mixed herbal medicine extracts showed better F055-1 (40.01%) than F055 (69.21%) as well as the edema suppression effect. Despite the fact that the jujube extract showed no inhibitory effect on the expression of IL-1β in the single extract, the inhibitory effect of F055-1 on IL-1β protein expression was superior to F055, unexpectedly.

In addition, as shown in Fig. 5, in the experimental group in which F055-1 was administered at a concentration of 150 mg / kg, an excellent inhibitory effect of IL-1?

As a result of the above results, the mixed herbal extracts F055 and F055-1 showed more excellent effect in treatment of gouty arthritis due to the synergistic effect than the single extract treatment group, and especially the effect of F055-1 You can see the best.

Gouty arthritis in animal models F055E  And F055E -1 efficacy evaluation

3-1. Identification of edema inhibition effect

In this example, the effect of suppressing edema of the F055E composition and F055E-1 composition prepared in Examples 1-3 and 1-4 was confirmed in the animal model of gouty arthritis by the same method as described in Example 2-1.

(F055E) containing 300 mg / kg of the herbal medicine ethanol composition (F055E) prepared by mixing the herbal medicine ethanol extract (F055E) and the herbal medicine ethanol composition 1) was administered at a dose of 300 mg / kg.

Solvent control (MSU) was administered 0.25% of CMC to MSU induced gouty arthritis, and positive control (Col) was administered colchicine to MSU induced gouty arthritis.

The thickness of the sole of each treatment group was measured based on 100% of the sole thickness of the solvent control (MSU) and expressed as a percentage in FIG. 6, and the lower the%, the better the suppression effect of edema.

As shown in FIG. 6, F055E-1 (82.2%) was more effective than F055E (92.7%) in suppressing the edema inhibition by administering ethanol extract of mixed herbal medicine at a concentration of 300 mg / kg. As a result, it was confirmed that F055E-1, which does not contain jujube extract, excellently suppresses edema in ethanol extracts as in water extracts.

3-2. On the weight bearing ratio  Identification of pain relief effect

The mouse model of Example 3-1 was administered with a F055E composition and a F055E-1 composition once a day for 4 days, followed by a dynamic weight bearing (DWB) device (Bioseb, Boulogne, France) ) Was used to determine the pain relief effect by measuring the weight of the hind legs (Fig. 7).

While the mouse was moving freely within the measuring device, the camera was attached to the top of the measuring device, and then the front and back legs of the mouse were recognized using the software, and the measured values of the load ratios of the respective feet were analyzed. Gout-induced arthritis-induced mice were reluctant to use MSU-administered normal feet for pain, so that the weight of both feet was not balanced and the weight of MSU-treated feet was relatively light. Using the measured foot weight (g), the body weight load ratio (%) was calculated. The above-mentioned weight load is a force to support and push on the foot. In normal case, the weight of both feet is balanced so that the weight load ratio (%) of one foot is 50%, but as the pain is increased, the weight load ratio .

Weight load ratio (%) = [weight of hind legs induced by ventilation / (total weight of hind legs)] × 100

As a result, as shown in FIG. 7, it was confirmed that the MSU induction resulted in a 40% reduction in the body weight load rate by about 10%, which was statistically significant. In contrast, in the F055E-treated group, the weight-bearing ratio was increased to 45.6% and in the F055E-1-treated group, the normal weight-bearing ratio was confirmed.

Goyosan  In an animal model F055E  And F055E -1 efficacy evaluation

Confirming the effect of serum uric acid reduction

(CMC-Na, pH 5.0) solution containing 0.1 M sodium acetate in SD-LETT (Orient Bio) in order to induce hyperuricemia. And 150 mg / kg of potassium oxonate was intraperitoneally injected. After 1 hour of administration of potassium oxonate, the 400 mg / kg F055E and F055E-1 compositions prepared in Examples 1-3 and 1-4 and the positive control 50 mg / kg Benzbromarone were added to 0.5% Of buffered saline (PBS) buffer solution containing carboyxlmethyl cellulose. The suspension was orally administered once. Two hours after the last oral administration, samples were anesthetized with ethyl ether. Blood was collected and the urine output was measured using a Biovision assay kit (USA).

As shown in FIG. 8, uric acid amount was increased to about 3.64 mg / dl by the administration of potassium oxonate (PO), and 2.50 mg / dl and F055E-1 (PO), and 25.58% and 25.45%, respectively, compared with the control group (PO).

Formulation Example 1. Preparation of a pharmaceutical composition

1-1. Manufacture of Powder

Creation, mixture of dandelion, dandelion, licorice and health extract 300 mg

Lactose 1000 mg

Talc 100 mg

The above components are mixed and filled in airtight bags to prepare powders.

1-2. Manufacture of tablets

Creation, mixture of dandelion, dandelion, licorice and health extract 300 mg

Corn starch 1000 mg

Lactose 1000 mg

Magnesium stearate 20 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

1-3. Preparation of capsules

Creation, mixture of ginger, dandelion, licorice and health extract 150 mg

Crystalline cellulose 30 mg

Lactose 148 mg

Magnesium stearate 2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

1-4. Injection preparation

Creation, mixture of ginger, dandelion, licorice and health extract 150 mg

180 mg mannitol

Sterile sterilized water for injection 2974 mg

Na ₂ HPO ₄ 2H ₂ O 26 mg

(2 ml) per 1 ampoule in accordance with the usual injection preparation method.

1-5. Manufacture of liquid agent

Creation, mixture of dandelion, dandelion, licorice and health extract 300 mg

10 g per isomer

5 g mannitol

Purified water quantity

Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.

Formulation Example 2. Preparation of Food Composition

2-1. Manufacture of health food

Creation, mixture of ginger, dandelion, licorice and health extract 150 mg

Vitamin mixture quantity

70 [mu] g of vitamin A acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

0.15 mg of vitamin B2

Vitamin B6 0.5 mg

0.2 [mu] g vitamin B12

Vitamin C 10 mg

Biotin 10 μg

Nicotinic acid amide 1.7 mg

50 ㎍ of folic acid

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

2-2. Manufacture of health drinks

Creation, a mixture of ginger, dandelion, licorice and health extract 100 mg

Vitamin C 15 g

Vitamin E (powder) 100 g

19.75 g of ferrous lactate

3.5 g of zinc oxide

Nicotinic acid amide 3.5 g

Vitamin A 0.2 g

Vitamin B1 0.25 g

Vitamin B2 0.3 g

Water quantification

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 for about 1 hour. The resulting solution was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, &Lt; / RTI &gt;

Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

Claims (8)

6 to 8: 2.5 to 5: 4 to 7: 1.5 to 3.5: 2.5 to 5.5 weight ratio, hyperactivity, hyperpigmentation, dermatitis, licorice and health extracts, A method for preventing or treating at least one disease selected from the group consisting of acute gouty arthritis caused by deposition of crystals, urinary incontinence, nephrolithiasis, and gouty nephropathy. delete delete delete 6 to 8: 2.5 to 5: 4 to 7: 1.5 to 3.5: 2.5 to 5.5 weight ratio, hyperactivity, hyperpigmentation, dermatitis, licorice and health extracts, Wherein the composition is for preventing or ameliorating at least one disease selected from the group consisting of acute gouty arthritis, urinary incontinence, nephrolithiasis, and gouty nephropathy caused by deposition of crystals. delete delete delete

Images