KR101203752B1 - Composition comprising Chioneceter japonicur for preventing and treating obesity or hyperlipidemia and atherosclerotic-vascular diseases - Google Patents

Abstract

The present invention relates to a composition for the prevention and treatment of obesity or hyperlipidemia and atherosclerotic vascular disease containing red crab as an active ingredient. Specifically, the red crab of the present invention is a lipid in liver tissue and feces in an animal model causing hyperlipidemia. Pharmaceuticals that are useful for the prevention and treatment of obesity or hyperlipidemia and atherosclerotic vascular disease have been found to reduce content, decrease triglycerides, cholesterol, phospholipids, lipid peroxide and Hydroxyl radical content in serum, and enhance SOD activity in serum. It can be used in the composition and dietary supplements.

Description

Composition comprising Chioneceter japonicur for preventing and treating obesity or hyperlipidemia and atherosclerotic-vascular diseases}

The present invention relates to a composition for the prevention and treatment of obesity or hyperlipidemia and atherosclerotic vascular disease containing red crab as an active ingredient.

[Document 1] 厚生 省 保健 醫療 局.地域 保健 健康 增進 榮 養 課 生活 習慣 病 對策 室. 1999 Lifestyle disease の し お り.東京.日本: 株式會社 社會 保險 出版社. (1999)

[Document 2] 厚生 統計 協會.國民 衛生 の 動向 Welfare Service 臨 時 增刊 44 券 9. 東京.日本. 1997

[Reference 3] Kang Jin-kyung's concept of lifestyle disease. Korean Medical Association. March 2004 issue. 188-190 (2004)

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Applegate, W.B., Hughes, J.P and Zwaag, R.V .: Case control study of oronary heart disease risk factors in elderly, J. Clin. Epidemiol, 44 (2): 409-415 (1991)

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[19] Mc Growan, M.w., Artiss, J.D and Stramdbergh, D.R .: Aperoxid ase-coupled method for the colorimetric determination of serum triglycerides, Clin. Chem., 29, 538 (1983)

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The concept of geriatric disease, which explained the conventional chronic degenerative disease that people know about everyday, introduced the concept of "life sickness" at the Japanese Ministry of Health, Public Welfare and Public Health in 1996 (1). A group of diseases related to the onset and progression of lifestyle such as 'lifestyle disease' was defined (2). Therefore, lifestyle disease is the primary preventive concept that can prevent the development and progression of disease through improvement of lifestyle, and the concept that lifestyle should be corrected from childhood (3, 4).

Smoking, hypertension, obesity, and hyperlipidemia are risk factors for atherosclerosis. Among these, hyperlipidemia refers to abnormally elevated levels of triglycerides and cholesterol in blood, ie, higher levels of serum lipids than normal (5, 6). The hyperlipidemia and hypertriglyceridemia are classified according to the type of increased lipid. Hyperlipidemia is mainly caused by excessive intake of lipid-rich diets (7, 8). The more precise cause is not due to excessive intake of meat, but an increase in blood lipids due to hyperglycemia or metabolic abnormalities of ingested lipids. It is caused by tissue damage caused by peroxidation (9, 10). Hyperlipidemia is one of the most important independent risk factors of cardiovascular disease, especially coronary artery disease, and elevated levels of cholesterol or triglycerides above normal increase arteriosclerosis, but decrease blood cholesterol levels, especially LDL-cholesterol levels or HDL- It is well known that increasing cholesterol reduces coronary artery disease (11). Hypertension, diabetes mellitus, hypercholesterolemia, smoking, obesity, and lack of exercise are pointed out as risk factors for coronary artery disease (12, 13), and dietary factors, including fat intake, have a significant effect on hypercholesterolemia and coronary artery disease It is said to be crazy (14). Hyperlipidemia drug therapy reported that there are two main guidelines for treating hyperlipidemia: lifestyle therapy (meal therapy to reduce saturated fat and cholesterol intake, weight loss, exercise therapy, etc.) and drug therapy. Among them, the synthetic drug used as a pharmacotherapy decreases LDL-cholesterol or triglyceride level, but has side effects such as abdominal pain, indigestion, hyperglycemia, retinopathy, insomnia and myopathy (15).

Red crab is scientific name Chioneceter japanicur , usually called crab or red crab in Korea. Because of its unique flavor and aroma, red crab is used by many people as a delicacy and in the manufacture of processed foods such as meat and gratin. The red crab is about 15% used for food and the remaining 85% is discarded as processed by-product. In this study, we tried to verify the physiological activity through animal experiments by dividing each part without extracting it by using red crab which is a special product of the east coast and extracting them with solvent.

Therefore, the present inventors studied the composition of the prevention and treatment of anti-obesity, hyperlipidemia, and atherosclerotic vascular disease of red crabs, and induced obesity and dietary hyperlipidemia by raising a sample prepared with the addition of an obesity inducing ingredient (beef tallow). It was confirmed that the blood crab administration group in the animal model reduced blood triglyceride and cholesterol content, and decreased the lipid content in liver tissue and feces in the animal model in which hypercholesterol induced by high cholesterol diet and triglyceride, cholesterol, phospholipid in serum To reduce the lipid peroxide and Hydroxyl radical content, and enhance the SOD activity in the serum, the present invention was confirmed to be useful for the prevention and treatment of obesity or hyperlipidemia and atherosclerotic vascular disease.

In order to accomplish the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of obesity or hyperlipidemia and atherosclerotic vascular disease containing red crab as an active ingredient.

The present invention also provides a health functional food for the prevention and improvement of obesity or hyperlipidemia and atherosclerotic vascular disease containing red crab as an active ingredient.

The red crab as defined herein includes a dry powder, a polar solvent soluble extract, or a polar solvent insoluble extract form.

The red crab as defined herein includes a red crab meat, a red crab leg shell or a red crab trunk shell, and preferably (1) the red crab dried powder is dried and powdered by conventional drying methods such as sun drying, natural drying and forced drying. Red crab dried powder (hereinafter referred to as “CJ-B”); (2) The red crab polar solvent soluble extract is a red crab extracted by a conventional extraction process using a polar solvent such as water, methanol, ethanol, butanol and the like, and a mixture thereof, preferably a mixed solvent of water and ethanol. Polar solvent soluble extract (hereinafter referred to as “CJ-1”); And (3) Hongge polar solvent insoluble extract (hereinafter referred to as "CJ-P") which is an insoluble residue in the polar solvent.

Hyperlipidemia and atherosclerotic vascular diseases as defined herein are specifically hyperlipidemia, arteriosclerosis, heart failure, hypertensive heart disease, arrhythmia, congenital heart disease, myocardial infarction, angina pectoris, stroke or peripheral vascular disease, preferably hyperlipidemia or arteriosclerosis to be.

Hereinafter, a method for obtaining a red crab polar solvent soluble extract and a red crab polar solvent insoluble extract of the present invention will be described in detail.

For example, a vacuum-frozen red crab sample is placed in a flask, followed by lower alcohols such as water, methanol, ethanol, butanol, and mixtures thereof, preferably a mixed solvent of water and ethanol, more preferably 80 to 100% ethanol. 10 to 50 minutes at 1 ° C. to 50 ° C., preferably 5 ° C. to 45 ° C. after addition of 1 to 20 times (w / v), preferably 2.5 to 10 times (w / v) of the sample amount. A first step of dividing into a red crab polar solvent soluble extract and a red crab polar solvent insoluble extract which is insoluble in the polar solvent, after ultrasonic extraction for 20 minutes to 40 minutes, followed by filtration using a vacuum filter; The second step of removing the solvent of each extract obtained above, concentrated at 5 ℃ to 45 ℃ with a rotary vacuum concentrator, lyophilized and stored at -5 ℃ to -60 ℃, preferably -10 ℃ to -50 ℃ Hong crab polar solvent soluble extract of the present invention through the manufacturing process of the, and the remaining residues can be dried to obtain a red crab polar solvent insoluble extract.

In the first step, the red crab is a red crab (Chioneceter japanicur).

The pharmaceutical composition of the present invention comprises the red crab in an amount of 0.1 to 50% by weight based on the total weight of the composition.

However, the composition is not limited thereto, and may vary depending on the condition of the patient, the type of disease, and the progress of the disease.

Since the red crab itself of the present invention has little toxicity and side effects, it is a drug that can be used safely even when taken for long periods of time.

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

The composition of the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions, Examples of carriers, excipients and diluents that can be included in the composition containing the extract 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 preparations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid preparations contain at least one excipient such as starch, calcium carbonate and sucrose in the powder. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium stearate 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. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

The preferred dosage of the composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the red crab of the present invention is preferably administered at 0.5 g / kg to 5 g / kg, preferably at 1 g / kg to 3 g / kg. The administration may be carried out once a day or divided into several doses. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.

The composition of the present invention may be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.

The present invention also provides a health functional food for the prevention and improvement of obesity or hyperlipidemia and atherosclerotic vascular disease containing red crab as an active ingredient.

The composition comprising the red crab of the present invention can be used in various ways, such as drugs, foods and beverages for the prevention and improvement of obesity or hyperlipidemia and atherosclerotic vascular disease. Foods to which the red crab of the present invention may be added include, for example, various foods, beverages, gums, teas, vitamin complexes, health supplements, and the like, and may be used in the form of powders, granules, tablets, capsules, or beverages. have.

The red crab of the present invention may be added to food or beverage for the purpose of preventing and improving obesity or hyperlipidemia and atherosclerotic vascular disease. At this time, the amount of the red crab in the food or beverage is generally added to the health food composition of the present invention to 1 to 5% by weight of the total food weight, the health beverage composition is 0.02 to 10 g based on 100 ml, preferably Can be added in a ratio of 0.3 to 1 g.

In addition to containing the red crab as an essential ingredient in the indicated ratio, the health beverage composition of the present invention is not particularly limited in the liquid component, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like Sugar, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of said natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 mL of the composition of the present invention.

In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

The red crab of the present invention reduces the lipid content of liver tissue and feces in the hyperlipidemia-induced animal model, reduces triglyceride, cholesterol, phospholipid, lipid peroxide and Hydroxyl radical content in serum, and enhances SOD activity in serum. It can be used in pharmaceutical compositions and health functional foods useful for the prevention and treatment of obesity or hyperlipidemia and atherosclerotic vascular disease.

Hereinafter will be described in detail by the reference examples, examples and experimental examples of the present invention.

However, the following Reference Examples, Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following Reference Examples, Examples and Experimental Examples.

Example 1 Preparation of Extracts and Extraction Residues

Vacuum frozen red crab (50g as dry weight) purchased from Seongjin Co., located in Sokcho-si, was placed in a 500mL Erlenmeyer flask, followed by adding 95% ethanol to 250mL of 5 times the sample volume (w / v), followed by 30 ℃. Ultrasonic extraction for 30 minutes at and filtered using a vacuum filter to divide the extracted extract and the residue. The extracted residue was stored at -20 ° C after removing ethanol at room temperature, and the ethanol extract was used for experimental analysis while removing the ethanol at 40 ° C with a reduced pressure concentrator and stored below -40 ° C. In the experiment (1) red crab ethanol extract (hereinafter referred to as "CJ-1A") and red crab ethanol extract residue (hereinafter referred to as "CJ-1AR") (2) red crab leg shell ethanol extract (hereinafter, " CJ-1B ”) and red crab leg ethanol extract residue (hereinafter referred to as“ CJ-1BR ”), (3) red crab trunk ethanol extract (hereinafter referred to as“ CJ-1C ”) and red crab trunk ethanol Extract residues (hereinafter referred to as “CJ-1CR”) were each obtained (see Table 1).

From dried red crab  Obtained extract yield
( Unit  g / 100 g) sample Red crab meat (g) Red crab leg shell (g) Red crab shell (g) Red crab 2.97 0.12 0.15

Reference Example  1. Preparation for Experiment

1-1. Animals & Aid

The SPF male 140 ± 10g Sprague-Dawley (SD) rats used in this study were purchased from [Hyochang Science Co., Ltd.] and used only for healthy animals after 1 week through quarantine, purification and breeding. . The breeding environment of this test was conducted in a laboratory animal breeding room (TECNIPLAST, Italy) set at a temperature of 22 ± 3 ℃, a relative humidity of 50 ± 10%, and an illumination time of 12 hours (07: 00 ~ 19: 00). Feed was freely ingested for drinking water, which was a solid feed for animals (Central Experimental Animal, Seoul). 24 hours before the experiment time only watering and fasting. At this time, the experimental animals were treated within a certain time (10:00 AM ~ 12:00 AM) in consideration of the daily variation of enzyme activity.

1-2. Animal diet administration method of experimental feed

Each sample was administered with oral needle zonde to each experimental group for 4 weeks at 200 mg / kg dose using 4% tween 80 diluted with physiological saline.

1-3. Statistical analysis

The results obtained in this experiment were expressed as mean ± standard deviation, and statistical significance was verified by Duncan's multiple range test.

Experimental Example  1. Hyperlipidemia experiment

1-1. Induction of hyperlipidemia

Induction of dietary hyperlipidemia in experimental animals is shown in Table 2. That is, a preparation sample containing beef tallow was raised for 6 weeks (see Table 2).

Foundation and Hyperlipidemic  Configuration Configuration Basic diet
(%) Hyperlipidemia
(%) Casein 20.0 20.0 DL - Methionine 0.3 0.3 Corn Starch 15.0 15.0 Sucrose 50.0 34.5 Fiber ^{One )} 5.0 5.0 Corn oil 5.0 - AIN - mineral Mixture ^{2 )} 3.5 3.5 AIN - vitamin Mixture ^{3 )} 1.0 1.0 Choline Bitartate 0.2 0.2 Beef Tallow - 20.5 ^One) Cellulose  : Sigma Co . LTD ., USA
²⁾ Rogers and Haper The mineral mixture according to the method of (1965) is as follows (g / kg diet ): Calcium phosphate divalent 500.0, sodium chloride 74.0, calcium citrate A mustache  220.0, calcium sulfate 52.0, magnesium oxide 24.0, magnesium carbonate 3.5, iron citrate 6.0, Zinc carbonate 1 .6, cupuric carbonate 0.3, potassium Iodide  0.01, chromium potassium sulfate 0.55, finely powdered with sucrose, adjusted to 1,000
³⁾ Vitamin mixture (g / kg diet ): Thiamine HCl  0.6, biotin 0.02, riboflavin 0.6, Cyanocobalamin  0.001, pyridoxine HCl  0.7, Retinyl  Acetate 0.8, nicotinic acid 3.0, DL Tocopherol 3.8, Ca - Pantothenate  1.6, 7- Dihydrocholesterol  0.0025, folic acid 0.2, methionine 0.005, with sucrose Fine powder  To 1,000

1-2. Serum and Enzyme  pharmacy

After the sample was injected, the animal was lightly anesthetized with CO ₂ , and blood was collected from the abdominal aorta. The collected blood was left for 30 minutes and centrifuged at 3,000 rpm for 10 minutes to separate serum and lipid, lipid peroxide, hydroxyl radical. The content and superoxide dismutase activity were measured.

1-3. Body weight and fat tissue weight measurement

Body weight change was measured every week from the start of the experiment, the weight of the adipose tissue was calculated by taking the fat around the abdominal cavity and testicles.

1-4. Liver tissue  And Feces  Lipid content measurement

Liver tissue was weighed and stored frozen at -70 ℃, feces collected for the last 4 days. Triglyceride and cholesterol were measured according to the method of Folch (16). In other words, the stools were lyophilized and ground to be powdered. The liver tissues were cut and then ground with a teflon homogenizer. 10 times the amount of solvent (chloroform: methanol = 2: 1) was added to the sample, and the lipids were repeatedly extracted. The filtrate was put in a water container and concentrated under reduced pressure to obtain lipids. Methanol was added thereto to dissolve well, and then quantified using a kit using an enzyme method.

1-5.Total Lipids Total lipid ) Content measurement

By the method of Fringe and Dunn (1980) using the principle of the sulfo-phospho-vanillin reaction, the absorbance was measured at 540 nm for the pink color, which was heated with concentrated sulfuric acid and added with vanillin phosphate. The blood content was expressed in mg / dl according to the standard calibration curve.

1-6. Total cholesterol ( Total cholesterol ) Content measurement

Experiments were carried out using a kit (AM 202-K, Asan) prepared by an enzyme method such as Richmond (18). Enzyme reagents (containing 20.5 U / l cholesterol, oxidase 10.7 U / l, and sodium hydroxide 1.81 g / l) were dissolved in enzyme reagent solution (potassium phosphate monobasic 13.6 g / l, phenol 1.88 g / l). 3.0 ml of the enzyme solution prepared in 20 μl of the sample was added to the dissolved solution, followed by incubation at 37 ° C. for 5 minutes, and the absorbance was measured at a wavelength of 500 nm based on the reagent blank. The blood content was expressed in mg / dl according to the standard calibration curve.

1-7. Triglyceride ( Triglyceride ) Content measurement

Experiments were performed using a kit (AM 157S-K, Asan) prepared according to the method of McGowan et al. (19). Enzyme reagent (containing lipoprotein lipase 10800U, glycerol kinase 5.4U, peroxidase 135000U, and L-α-glycero phosphooxidase 160U) in ice cold phase was dissolved in enzyme reagent [N, N-bis (2-hydroxyethyl) -2-aminomethane sulfonic acid 0.427 g / dl containing 3.0 ml of the enzyme solution prepared in 20 μl of the sample was added to the solution, and then incubated at 37 ° C. for 10 minutes to measure absorbance at a wavelength of 550 nm based on a reagent blank. The blood content was expressed in mg / dl according to the standard calibration curve.

1-8. Phospholipids ( Phospholipid ) Content measurement

Experiments were carried out using a kit (Iatron Chem. Co.) prepared by the enzyme method of Chen et al. (20). In an ice cold solution, 20 µl of enzyme reagent (containing phospholipase 3.9U, choline oxidase 5.6U, peroxidase 3.6U, 4-aminoantipyrine 0.3252 mg) dissolved in enzyme reagent solution [containing tris (hydroxymethyl) -aminomethane 6.057 mg]. 3.0 ml of the prepared enzyme solution was added and incubated at 37 ° C. for 20 minutes to measure absorbance at a wavelength of 500 nm. The content was expressed in mg / dl according to the standard calibration curve.

1-9. High density lipoprotein - cholesterol ( HDL -C) content determination

The experiment was carried out using a kit (AM 203-K, Asan) prepared by the enzyme method of Noma et al. (21). 0.2 ml of sedimentation reagent (containing dextran sulfate 0.1% and magnesium chloride 0.1M) was added to 20 µl of serum and mixed well. 0.1 ml of the supernatant was mixed well with 3.0 ml of enzyme solution, incubated at 37 ° C. for 5 minutes, and the absorbance was measured at a wavelength of 500 nm using the reagent blank as a control. The content was expressed in mg / dl according to the standard calibration curve.

1-10. LDL - cholesterol  Content measurement

Low density lipoprotein-cholesterol (LDL-C) content was calculated by Equation 1 according to the method of Fridewald (22).

1-11. Blood Lipid peroxide  Content measurement

According to the method of Yagi et al. (23), 4.0 ml of 1 / 12N H ₂ SO ₄ was added to 20 µl of serum, mixed with 0.5 ml of 10% phosphotungstic acid, and allowed to stand at room temperature for 5 minutes, followed by centrifugation to take only precipitated serum protein. Then, 2.0 ml of 1 / 12N H ₂ SO ₄ and 0.3 ml of 10% phosphotungstic acid were added thereto, followed by centrifugation. 1.0 ml of a solution of 4.0 ml of distilled water, a mixture of 0.67% thiobarbituric acid and acetic acid in a 1: 1 manner was added thereto, and the mixture was reacted at 95 ° C. for 60 minutes, cooled at room temperature, and 5.0 ml of n-BuOH was added. After centrifugation for a minute, the resulting red n-BuOH was taken and the absorbance was measured using a spectrofluorometer (Ex: 515 nm, Em: 553 nm). The absorbance was measured by reacting tetraethoxypropane 0.5 nmole with the standard solution in the same manner, and the serum lipid peroxide content was calculated by Equation 2 below.

1-12. Blood Hydroxyl radical  Content measurement

According to the method of Kobatake et al. (24), it was added to 34.8 μl of serum to 333.3 μl as 0.54 M NaCl, 0.1 M potassium phosphate buffer (pH 7.4), 10 mM NaN ₃ , 7 mM deoxyribose, 5 mM ferrous ammonium sulfate, and distilled water. The mixture was allowed to stand at 37 ° C. for 15 minutes. 67 μl of serum was taken and mixed with 75 μl of 8.1% sodium dodecyl sulfate, 500 μl of 20% acetic acid and 25 μl of distilled water. 333 μl of 1.2% thiobarbituric acid was added thereto, followed by heating in a water bath (100 ° C.) for 30 minutes, cooling at room temperature, and centrifugation at 700 × g for 5 minutes to measure absorbance at a wavelength of 532 nm. The content of hydroxyl radical (nmole / mg protein) was quantified by the calibration curve.

1-13. Blood Superoxide dismutase ( SOD ) Active measurement

It was quantified according to the method of Oyanagui (25). The serum was diluted 100-fold with potassium phosphate buffer and 100 μl of this was added to the test tube, where 500 μl of re-distilled water, 200 μl of reagent A (3 mM hydroxylamine / 3 mM hypoxanthine) and reagent B (7.5 mU / ml xanthine oxidase (XO) with Add 200µl of 0.1mM EDTA-2Na), mix well, and let stand for 40 minutes in 37 ℃ water bath. 2.0 ml of Reagent C (300 of sulfanilic acid / 5.0 mg N-1-naphthyl-ethylenediamine in 500 ml of 16.7% acetic acid) was added to the reaction solution, which was allowed to stand at room temperature for 20 minutes, and then the absorbance was measured at 550 nm. The superoxide dismutase activity in serum was measured. Enzyme activity was expressed as U / mg protein of superoxide dismutase. One unit of SOD was calculated as 50% inhibition of adrenochrome production.

1-14. Protein quantification

Protein content was measured using bovine serum albumin (Sigma, Fr. V) as a standard according to the method of Lowry (26).

2. Experimental results

2-1. Weight change

Body weight was measured every week from the start of the experiment, and the weight of the adipose tissue was measured after taking the abdominal cavity and the peri testicular fat on the last day of the experiment and are shown in Table 3 (see Table 3). As a result, 6 weeks of high cholesterol diet intake of hyperlipidemia induced 6 weeks of body weight was 325.4 ± 21.6g compared to normal group (6 weeks, 210.6 ± 19.7g) of about 54% weight It was confirmed that the increase. In addition, as a result of administering the red crab fraction to the hyperlipidemic test animals, the weight gain phenomenon was alleviated in the experimental group administered with the red crab fraction compared to the hyperlipidemic diet group, and the red crab shell portion was more effective than the red crab meat, especially the red crab trunk ethanol extract cup. It was confirmed that the object administration group showed the best effect as 280.5 ± 14.7g. In addition, as shown in Table 4, compared with the hyperlipidemia diet group, all the experimental groups of the red crab fraction administration group were able to confirm the reduction effect of the abdominal cavity and peritesticular fat tissue weight. Yes, it was confirmed (see Table 4). It is thought that red crab shell powder (chitin) has the same water retention as water-soluble fiber, which increases the time spent on the stomach, thus providing a feeling of satiety and delaying digestive absorption of nutrients (27).

Normal and 4 weeks High-fat diet  Ingested Rat  Effect of Individual Red Crab on Weight Treatment Dose
( mg Of kg ) Weight loss One 2 3 4 5 6 Normal 72.9 ± 7.25 b 110.8 ± 12.3 b 139.6 ± 19.4 b 176.4 ± 21.4 b 203.5 ± 22.5 c 210.6 ± 19.7 e Control group 83.7 ± 8.16 a 151.4 ± 11.7 a 211.8 ± 20.7 a 251.6 ± 19.8 a 310.6 ± 25.4 a 325.4 ± 21.6 a Red crab meat 200 78.2 ± 7.11 ab 148.6 ± 13.5 a 212.3 ± 19.8 a 248.7 ± 21.8 a 298.2 ± 19.1 ab 315.6 ± 18.9 abc CJ-1A 200 81.6 ± 6.45 ab 149.2 ± 13.9 a 209.6 ± 21.7 a 253.9 ± 13.7 a 295.4 ± 20.6 ab 320.3 ± 17.7 ab CJ-1AR 200 75.4 ± 6.52 ab 150.3 ± 14.8 a 210.7 ± 18.8 a 249.2 ± 16.4 a 297.1 ± 14.7 ab 315.8 ± 15.2 abc Hong crab leg shell 200 73.7 ± 8.17 ab 151.7 ± 12.6 a 213.6 ± 22.6 a 241.6 ± 18.6 a 286.5 ± 21.6 ab 296.5 ± 18.3 CD CJ-1B 200 75.4 ± 6.47 ab 149.8 ± 13.4 a 217.4 ± 21.3 a 250.3 ± 17.3 a 294.2 ± 13.2 ab 300.6 ± 19.8 bcd CJ-1BR 200 76.2 ± 7.42 ab 153.6 ± 12.9 a 212.6 ± 21.5 a 237.8 ± 19.2 a 273.3 ± 18.6 b 280.5 ± 14.7 d Hong crab shell 200 73.4 ± 8.06 b 150.9 ± 14.1 a 211.3 ± 23.4 a 243.2 ± 18.5 a 290.2 ± 14.5 ab 300.9 ± 18.6 bcd CJ-1C 200 80.6 ± 8.25 ab 148.7 ± 13.7 a 210.2 ± 21.8 a 248.5 ± 20.1 a 298.6 ± 16.2 ab 295.4 ± 14.9 CD CJ-1AR 200 81.1 ± 7.26 ab 151.2 ± 14.0 a 216.4 ± 22.2 a 240.5 ± 16.4 a 281.9 ± 15.4 b 285.2 ± 15.6 d 6 weeks On high paper  Obese by Rat is  Each day for 4 weeks, Oral level After 24 hours of last treatment of each site, red crabs were killed. The essay process is an experimental method Is described .
The figures are expressed as mean ± S.D of the six experiment results. Figures that follow the same letter Significantly  Not different (p <0.05).

I added the red crab sample for 4 weeks Dietary  Effect of Abdominal and Epididymal Adipose Tissue Weight on Rats Treatment Dose
( mg Of kg ) Abdominal cavity Epididymis mg  / g of body weight Normal 6.73 ± 2.12 e 8.27 ± 1.83 d Control group 14.6 ± 3.16 a 12.8 ± 2.11 a Red crab meat 200 13.9 ± 2.62 ab 12.5 ± 1.42 ab CJ -1A 200 13.7 ± 1.87 abc 12.1 ± 1.36 ab CJ -One AR 200 14.1 ± 1.42 ab 12.3 ± 1.25 ab Hong crab leg shell 200 11.3 ± 2.61 bcd 10.9 ± 1.47 abc CJ -1B 200 13.5 ± 1.38 abc 12.1 ± 1.63 ab CJ -One BR 200 9.62 ± 2.25 d 9.43 ± 1.42 CD Hong crab shell 200 12.5 ± 2.10 abc 11.4 ± 1.37 ab CJ -1C 200 13.4 ± 2.13 abc 12.3 ± 1.45 ab CJ -One CR 200 10.9 ± 1.92 CD 10.5 ± 1.38 bc The essay process is an experimental method Is described . The figures are expressed as mean ± S.D of the six experiment results. Figures that follow the same letter Significantly  Not different (p <0.05).

2-2. Lipids in serum ( lipid ) content

As shown in Table 5, the blood lipid levels of hyperlipidemic rats were 18% phospholipid and 172% triglyceride compared to the rats fed the normal diet, and the increase in triglyceride levels was particularly high (see Table 5). The amount of phospholipids in the experimental group treated with the red crab fraction did not show a significant difference compared to the hyperlipidemia diet and the experimental group, but the neutral lipid content alleviated the increase in the experimental group. In particular, it was confirmed that the extract of Hong crab trunk bark showed the highest reduction rate by about 26% reduction compared to the content of triglyceride in the hyperlipidemia diet group.

Sample red crab for 4 weeks After oral administration Serum Lipids  Concentration change result Treatment Dose
( mg Of kg ) Phospholipid Triglyceride mg  Of dl Normal 127.7 ± 20.3 a 71.3 ± 7.43 f Control group 151.3 ± 18.7 a 194.5 ± 10.6 a Red crab meat 200 149.8 ± 14.2 a 182.3 ± 9.7 abc CJ -1A 200 147.3 ± 18.9 a 186.7 ± 11.3 ab CJ -One AR 200 150.6 ± 19.6 a 180.4 ± 10.8 bc Red crab meat  Leg shell 200 150.8 ± 16.5 a 163.9 ± 10.1 bc CJ -1B 200 148.3 ± 17.3 a 185.2 ± 9.9 ab CJ -One BR 200 146.2 ± 18.8 a 142.9 ± 11.3 e Red crab meat  Torso 200 149.3 ± 15.4 a 170.7 ± 14.6 CD CJ -1C 200 148.1 ± 16.1 a 182.4 ± 10.8 abc CJ -One CR 200 147.1 ± 14.5 a 151.3 ± 10.4 e The essay process is an experimental method Is described .
The figures are expressed as mean ± S.D of the six experiment results. Figures that follow the same letter Significantly  Not different (p <0.05).

2-3. Serum cholesterol ( cholesterol ) Content change and arteriosclerosis index

The results of investigating the effect of the red crab fraction on the change of serum cholesterol content and arteriosclerosis index in rats induced by hyperlipidemia due to high cholesterol diet (see Table 6) are shown. The total cholesterol content in the blood increased to 88.7 ± 5.25mg / dL due to the induction of hyperlipidemia. In particular, the ethanol extract residue of Hongge crab shell was 65.8 ± 4.37mg / dL (about 26%), and the highest reduction was confirmed. There are studies showing that chitin affects blood lipid concentrations (28, 29). Compared with these previous studies, the diet of red crab shell powder has a lowering effect on plasma cholesterol levels. It seems to have played a role in inhibiting the absorption of. The HDL-cholesterol and LDL-cholesterol levels were not significantly different between the hyperlipidemic group and the red crabmeat group, but the red crab shells increased the HDL-cholesterol level and lowered the LDL-cholesterol level. Proved effective. Atherosclerotic index (AI) was 1.72 ± 0.11mg / dL in hyperlipidemic rats, and there was no significant difference between the groups of red crab meat and red crab shell ethanol extract. The arterial stiffness index of the administration group was lowered, and the ethanol extract residue of the red crab body shell was the lowest with 0.70 ± 0.12mg / dL. It was found out.

Effect of Red Crab Sample on Serum Cholesterol Content and Atherosclerosis Index after Oral Administration for 4 Weeks Treatment Dose
( mg Of kg ) Cholesterol ( mg  Of dl ) Total HDL LDL AI Normal 56.4 ± 6.13 e 41.8 ± 3.14 a 2.47 ± 0.92 d 0.35 ± 0.07 f Control group 88.7 ± 5.25 a 32.6 ± 2.96 de 7.83 ± 1.11 a 1.72 ± 0.11 b Red crab meat 200 87.3 ± 6.18 ab 30.3 ± 3.18 e 7.69 ± 0.83 a 1.88 ± 0.09 a CJ -1A 200 86.9 ± 4.17 ab 31.8 ± 2.17 e 7.77 ± 0.75 a 1.73 ± 0.13 b CJ -One AR 200 85.2 ± 5.06 ab 32.5 ± 3.25 de 7.65 ± 0.65 a 1.62 ± 0.08 b Hong crab leg shell 200 71.3 ± 4.25 ed 36.3 ± 2.25 bc 6.32 ± 0.61 b 0.96 ± 0.10 d CJ -1B 200 84.6 ± 5.19 ab 32.4 ± 2.37 de 7.53 ± 0.76 a 1.61 ± 0.05 b CJ -One BR 200 65.8 ± 4.37 d 38.6 ± 1.98 b 5.25 ± 0.63 c 0.70 ± 0.12 e Hong crab shell 200 73.8 ± 5.19 c 35.2 ± 2.08 CD 6.53 ± 0.58 b 1.10 ± 0.15 c CJ -1C 200 81.9 ± 4.92 b 31.3 ± 1.83 e 7.58 ± 0.70 a 1.62 ± 0.13 b CJ -One CR 200 67.7 ± 5.06 CD 37.5 ± 2.11 bc 5.87 ± 0.52 bc 0.81 ± 0.14 e The essay process is an experimental method Is described . The figures are expressed as mean ± S.D of the six experiment results. Figures that follow the same letter Significantly  Not different (p <0.05).
AI ( Atheroscrelosis Index ) = ( total cholesterol  - HDL cholesterol ) Of HDL  cholesterol

2-4. Lipids in liver tissue ( lipid ) And cholesterol ( cholesterol Change in content

The results of experiments on the change of lipid and cholesterol content in hepatic tissues after oral administration of red crab fractions to rats induced dietary hyperlipidemia are shown in Table 7 (see Table 7). In rats fed dietary hyperlipidemia with oral administration of the red crab fraction, the total lipid, triglyceride, and cholesterol contents in the liver tissues were significantly different between the red crab meat and the red crab skin ethanol extract compared with the hyperlipidemic diet group. However, the content of the red crab shell and the red crab shell ethanol extract residue was low. This suggests that the administration of the red crab shell and the ethanol extract of the red crab shell affects the lipid metabolism of the liver tissue, and indirectly proves that it is also effective in diseases such as hyperlipidemia. It was similar to the cholesterol lowering effect in liver (30, 31).

Effect of Lipid and Cholesterol Contents in Liver Tissues after Oral Administration of Red Crab Samples for 4 Weeks Treatment Dose
( mg Of kg ) Total lipid Triglyceride Cholesterol mg  / g of tissue Normal 16.4 ± 2.16 g 10.2 ± 0.98 g 2.97 ± 0.38 d Control group 32.8 ± 3.17 a 26.8 ± 1.43 a 6.52 ± 0.92 a Red crab meat 200 32.9 ± 2.13 a 25.4 ± 1.37 abc 6.37 ± 0.83 a CJ -1A 200 31.4 ± 1.97 a 25.8 ± 1.45 ab 6.25 ± 0.72 a CJ -One AR 200 31.5 ± 2.11 a 24.3 ± 1.97 bcd 6.31 ± 0.87 a Hong crab leg shell 200 25.7 ± 1.86 de 20.6 ± 1.41 e 4.63 ± 0.46 bc CJ -1B 200 28.8 ± 2.06 bc 24.8 ± 1.36 bc 5.88 ± 0.53 a CJ -One BR 200 20.9 ± 1.43 f 17.4 ± 1.28 f 3.92 ± 0.48 c Hong crab shell 200 27.3 ± 1.82 CD 22.7 ± 1.25 d 5.1 ± 0.39 b CJ -1C 200 30.7 ± 1.77 ab 23.9 ± 1.30 CD 6.04 ± 0.47 a CJ -One CR 200 23.5 ± 1.63 e 19.2 ± 1.31 e 4.42 ± 0.35 bc The essay process is an experimental method Is described . The figures are expressed as mean ± S.D of the six experiment results. Figures that follow the same letter Significantly  Not different (p <0.05).

2-5. Blood MDA Change in the content of, hydroxyl radical  Generated and superoxide dismutase ( SOD ) activation

As a result, as shown in Table 8, the content of MDA, a lipid peroxidation product, in the serum of the hyperlipidemia-induced hypercholesterolemic rats after 4 weeks of high cholesterol diet was lower than the hyperlipidemic group, especially in the crab body. The MDA content of the skin ethanol extract residue was low (see Table 8). Hydroxyl radical in the hyperlipidemia diet group was 5.73 ± 0.52nmole / mg, which was about doubled compared to the normal diet (2.87 ± 0.49nmole / mg). Compared with the group, it was confirmed that the reduction of the hydroxyl radical in the serum was less. In addition, it was confirmed that the superoxide dismutase (SOD) activity to remove the active oxygen was significantly enhanced in all the administration group, especially the active oxygen removal capacity of the ethanol extract residue of the red crab body shell was the most enhanced.

The lipid peroxidation product in the serum of rats fed the red crab sample for four weeks. MDA Content of Treatment Dose
( mg Of kg ) TBARS Hydroxy radical SOD MDA nmol Of mg protein nmol Of mg protein Unit Of mg protein Normal 28.1 ± 2.92 f 2.87 ± 0.49 c 3.56 ± 0.36 a Control group 52.9 ± 2.48 a 5.73 ± 0.52 a 1.77 ± 0.27 d Red crab meat 200 48.3 ± 3.11 b 5.39 ± 0.39 ab 1.87 ± 0.29 d CJ -1A 200 48.7 ± 2.73 b 5.47 ± 0.31 ab 1.88 ± 0.30 d CJ -One AR 200 47.8 ± 2.62 b 5.51 ± 0.25 ab 1.92 ± 0.43 d Hong crab leg shell 200 43.2 ± 2.53 d 5.07 ± 0.26 ab 2.25 ± 0.35 bcd CJ -1B 200 47.5 ± 2.48 d 5.45 ± 0.39 ab 1.98 ± 0.34 CD CJ -One BR 200 39.9 ± 2.51 e 4.69 ± 0.42 ab 2.58 ± 0.22 b Hong crab shell 200 43.9 ± 2.37 CD 5.19 ± 0.35 ab 2.11 ± 0.36 bcd CJ -1C 200 46.8 ± 2.46 bc 5.41 ± 0.28 ab 1.92 ± 0.25 d CJ -One CR 200 41.6 ± 2.33 de 4.87 ± 0.33 ab 2.43 ± 0.28 bc The essay process is an experimental method Is described . The figures are expressed as mean ± S.D of the six experiment results. Figures that follow the same letter Significantly  Not different (p <0.05).
Unit  : SOD The unit of about 50% in the blood Alkaline DMSO -Brokerage adrechrome It is defined as the suppression of reduction of.

Hereinafter, the formulation examples of the composition including the red crab of the present invention will be described, but the present invention is not intended to limit the present invention but is only intended to be described in detail.

Formulation example  One. Sanje  Produce

CJ-1 20 mg

Lactose 100 mg

Talc 10 mg

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

Formulation example  2. Preparation of tablets

CJ-1A 10 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

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

Formulation example  3. Preparation of capsules

CJ-1C 10 mg

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 0.2 mg

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

Formulation example  4. Preparation of injections

CJ-1B 10 mL

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na ₂ HPO ₄ , 12H ₂ O 26 mg

(2 ml) per 1 ampoule according to the usual injection preparation method.

Formulation example  5. Liquid  Produce

CJ-1 20 mL

10 g of isomerized sugar

5 g of mannitol

Purified water

Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, 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 adjusted to 100 ml with purified water, And sterilized to prepare a liquid preparation.

Formulation example  6. Manufacture of health food

CJ-P 1000 mL

Vitamin mixture proper amount

70 μg of Vitamin A Acetate

Vitamin E 1.0 mg

0.13 mg vitamin B1

0.15 mg of vitamin B2

0.5 mg vitamin B6

0.2 μg of vitamin B12

Vitamin C 10 mg

10 μg biotin

Nicotinic acid amide 1.7 mg

50 μg folic acid

Calcium pantothenate 0.5 mg

Mineral mixture

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

15 mg of potassium phosphate monobasic

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.

Formulation example  7. Manufacture of health drinks

CJ-1 1000 mL

Citric acid 1000 mg

100 g oligosaccharides

Plum concentrate 2 g

1 g of taurine

Add 900 ml of purified water

After mixing the above components according to a conventional healthy beverage production method, and then stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained by sterilization in a sterilized 2 L container, sealed sterilized and then stored in the present invention For the preparation of healthy beverage compositions.

Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.

Claims (8)

A pharmaceutical composition for the prevention and treatment of obesity, hyperlipidemia, or atherosclerosis, which contains a polar solvent insoluble extract of a red sea crab (Chioneceter japonicur) leg shell or a red sea crab (Chioneceter japonicur) body shell as an active ingredient. delete delete delete delete delete Health functional food for the prevention and improvement of obesity, hyperlipidemia, or atherosclerosis, which contains a polar solvent insoluble extract of red crab (Chioneceter japonicur) leg shell or red crab (Chioneceter japonicur) body shell as an active ingredient. delete