KR101017734B1 - A composition comprising the dried powder of Squid fraction or the extract thereof for preventing and treating hyperlipidemia - Google Patents

Abstract

The present invention relates to a composition for the prevention and treatment of hyperlipidemia comprising a squid fraction dry powder or extract as an active ingredient. Specifically, the dried squid fraction dry powder or extract of the present invention has a significant content of triglyceride in blood of an animal model of hyperlipidemia. Since the antihyperlipidemic effect is reduced by reducing the composition, the composition may be usefully used as a pharmaceutical composition or health functional food for the prevention and treatment of hyperlipidemia.

Squid, Blood Triglyceride, Cholesterol, Hyperlipidemia, Poloxamer-407

Description

Composition for preventing and treating hyperlipidemia comprising squid fraction dry powder or extract as an active ingredient {A composition comprising the dried powder of Squid fraction or the extract conjugate for preventing and treating hyperlipidemia}

The present invention relates to a pharmaceutical composition or health functional food for the prevention and treatment of hyperlipidemia containing a squid fraction dry powder or extract as an active ingredient.

[Document 1] Ki-Wan Lee and 4, Evaluation of 100 Years of Korean Dietary Life (Ⅰ), Shinkwang Publishing Co., 1998

[Document 2] Eun-Kyung Kim et al. 4, Life Cycle Nutrition, Shinkwang Publisher, 2005

[Reference 3] Cho Seong-hee, Geology and Atherosclerosis, Korean Journal of Nutrition and Nutrition, 23 (1) , pp.170-179, 1994

[Reference 4] Korea Food Industry Association Food Research Institute, A Study on the Relationship between Nutrition and Special Diseases, 1988

[Reference 5] 山 本 章, The Journal of Nihon Keinuke, 內科, 81 (2) , pp.237-242

S. Urano et al., Vitamin E and the susceotibility of erythocytes and reconstituted liposomes to oxidative stress in aged diabtices, Lipid . 26 , pp. 58-61, 1991

RS Sohal & R, G. Allen, Oxidative stress as a casual factor in determination and again (A unifying hypothesis.Exp), Gerontol, 25 , pp. 499-522, 1990

Schoen FJ et al., Robbins pathologic basis of disease, 5th ed. , pp. 473-484, 1994

Keys A. et al., Serum cholesterol respone to change in the diet, Metabolism 14 , pp. 747-758, 1965

Document 10 Sander. TAB et al., Conflicting roles of poly-unsaturated fatty acid, Lancet, I, pp.645-657, 1980

[11] Sander. TAB et al., Effect or blood lipids and haemostasis of a supplement of cod liver oil, rich in EPA and DHA in healthy young man, Clin. Sci, 61 , pp. 317-324, 1981

[Reference 12] Kyusan Mountain, 魚油, そ の 營養 と 復 權, pp.1-27, 1982

Dyerberg J., in "Nutritional evaluation of long-chain fatty acids in fish oil" (Barlow and Stans by by ed.) Academic Press, New York, pp. 245-261, 1982

Document 14 Bang. HO et al., The composition of food consumed by greenl and Eskimos, Acta Med Scand, 200 , pp.69-73, 1976

Reference 15 Hirai. A. et al., Eicosapentaenoic acid and platelet function in Japanese, Lancet, II. pp. 1132-1133, 1980

[Reference 16] Tawasawa, 藤田 孝天 E, PA の 生理 活性 果, 食品 工業, 9 下 , pp.53-59, 1985

Bronsgeest-Schoute, H. et al., The effect of varions intakes of ω3 fatty acids on the blood lipid composition in healthy human subjects, Am, J. clin Nuitr, 34 , pp.1752-1757, 1981

18 O'Dea, K., and A. J. Sinclair, Increased propotion of arachidonic acid in plasma lipids after 2 weeks on a diet of tropical seafood, 1982

[Ref. 19] Kook Seung-rae et al., Journal of Family Medicine, 18 (3) , pp.317-327, 1997

20 Ham IH et al., Kor. J. Herbology, 20 , pp. 45-52, 2005

[21] Lee HH et al., Kor. J. Anesthesiol, 40 , pp. 515-521, 2001

22 J Choi et al., J. Kor. Pharm. Sci., 18 , pp. 240-241, 1988

23 K Kim et al., J. Kor. Pharm. Sci., 28 , pp. 15-23, 1998

24 Nash VJ et al., Pharmacotherapy, 16 , pp. 10-15, 1996

25. Stellato C. et al., Br. J. Anaesth., 67 , pp. 751-758, 1991

26 Wout GM et al., J. Paren. Sci. Technol., 46 , pp. 192-200, 1992

[Article 27] Lee, Yeon-Sil et al. 3, Effect of the extract of the seaweed algae on lipid metabolism. Journal of Biochemistry, 35 (2) , pp.143-146, 2004

28. McGowan, MW et al., A peroxidase-coupled method for the colorimetric determination of serum triglycerides. Clin. Chem. 29 , pp. 538-542, 1983

Disease is a part of human life, and its pattern has changed with age. The economic development and high industrialization, rapid population growth and densification, environmental and health hygiene, and the development of new therapies that our society has experienced over the past 100 years have changed the disease structure of our people more than ever before. Brought. Korea's disease structure is shifting from infectious disease to adult disease, and the morbidity and mortality are changing accordingly (Kiwan et al., 4, 100-year evaluation of Koreans' diet (I), Shinkwang Publishing Co., 1998) In terms of structure, tuberculosis, bronchitis, gastroenteritis, etc. occupied the upper ranks before the 1950s. ) Accounted for 23.4% of all deaths (Kim Eun-kyeong et al. 4, Life Cycle Nutrition. Shinkwang Publishing Co., 2005). Cardiovascular disease is a major cause of premature mortality worldwide and is a multifactorial disease caused by genetics and other environmental factors. It has been reported to be closely related to lipid nutrition (Cho Sung-Hee, Lipid and Arteriosclerosis, Korea Nutrition) Korean Journal of Food Science and Technology 23 (1) , pp.170-179, 1994; Korean Food Industry Association Food Research Institute, A Study on the Relationship between Nutrition and Special Diseases, 1988).

Hyperlipidemia is the case where the concentration of serum lipids is higher than normal (山 本章, 의 學, 內科, 81 (2) , pp.237-242). Hyperglycemia or metabolic abnormalities of ingested lipids result in increased blood lipids or tissue damage due to lipid peroxidation (S. Urano et al., Vitamin E and the susceotibility of erythocytes and reconstituted liposomes to oxidative stress in aged diabtices, Lipid, 26 , pp. 58-61, 1991; RS Sohal & R, G. Allen, Oxidative stress as a casual factor in determination and again (A unifying hypothesis.Exp), Gerontol, 25 , pp. 499-522 , 1990).

In hyperlipidemia, the major components of increased serum lipid components are composed of fat-soluble substances such as cholesterol, triglycerides, phospholipids, and free fatty acids, and hypercholesterinemia, depending on which of these lipid substances increases mainly. It is called hypertriglyceridemia. Increased serum cholesterol and triglycerides are the most common causes of hyperlipidemia. Accumulation of excess fat causes blood circulation disorders and microcirculation failure, resulting in atherosclerosis, ischemic heart disease, cerebral infarction, hypertension, obesity and diabetes. (Schoen FJ et al., Robbins pathologic basis of disease, 5th ed. , Pp . 473-484, 1994).

In fact, cholesterol is an essential ingredient for normal functioning of the human body, a nutrient necessary for making cells, and a component of various hormones such as corticosteroids, male hormones, and female hormones. do. In addition, cholesterol is a nutrient necessary for the human body such as being used as a constituent of biological membranes and as a starting material for hormonal synthesis. However, excessive cholesterol intake is known to accumulate in blood vessels and cause cardiovascular diseases.There is no preventive method except low-cholesterol diet, and taking drugs such as cholesterol-lowering drugs is effective. Use is extremely limited due to reasons such as causing side effects such as liver dysfunction.

Since dietary cholesterol and saturated fatty acids raise blood cholesterol, unsaturated fatty acids, especially ω-6 linoleic acid, have been reported to lower blood cholesterol, limiting the intake of cholesterol and increasing the intake of unsaturated fatty acids. Ancel Keys has reported that it is very important for the treatment of cancer (Keys A. et al., Serum cholesterol respone to change in the diet, Metabolism 14 , pp. 747-758, 1965). The new evaluation of the so-called "back blue fish" has taken place because of increased interest in the nutritional value and physiological activity of polyunsaturated fatty acids, which are widely distributed in these red meat lipids (Sander. TAB et al., Conflicting roles). of poly-unsaturated fatty acid, Lancet, I, pp.645-657, 1980; Sander.TAB et al., Effect or blood lipids and haemostasis of a supplement of cod liver oil, rich in EPA and DHA in healthy young man, Clin.Sci , 61 , pp.317-324, 1981; K.S.O., ,, そ の 營養 と 復 權, pp.1-27, 1982; Dyerberg J., in "Nutritional evaluation of long-chain fatty acids in fish oil (Barlow and Stans by by ed.) Academic Press, New York, pp. 245-261, 1982; Bang.HO et al., The composition of food consumed by greenl and Eskimos. Acta Med Scand, 200 , pp.69 -73, 1976; Hirai.A. Et al., Eicosapentaenoic acid and platelet function in Japanese, Lancet, II, pp. 1132-1133, 1980). These lipids are characterized by containing large amounts of ω-3 polyunsaturated fatty acids with 20 or more carbon atoms, the main ones being eicosapentaenoic acid (20: 5, ω-3) and DHA (dicosahexaenoic acid, 20: 6, ω- 3) and other long chain monoene acids. In vivo, EPA and DHA have been known to convert into bioactive substances such as prostaglandin (PG) and leukotrien (LT) to prevent adult diseases such as thrombosis and myocardial infarction (泰和 彦, 藤田 孝天 E, PA の 生理 活性 果, 食品 工業, 9 下 , pp.53-59, 1985), This fact is described by Greenberg Eskimo (Dyerberg J., in "Nutritional evaluation of long-chain fatty acids in fish oil" (Barlow and Stans by by ed.) Academic Press, New York, pp. 245-261, 1982; Bang; HO. Et al., The composition of food consumed by greenl and Eskimos, Acta Med Scand, 200 , pp.69-73, 1976) Results of fish oil intake (Sander. TAB et al., Effect or blood lipids and haemostasis of a supplement of cod liver oil, rich in EPA and DHA in healthy young man, Clin.Sci , 61 , pp.317-324, 1981; Bronsgeest-Schoute, H. et al., The effect of varions intakes of ω3 fatty acids on the blood lipid composition in healthy human subjects, Am, J. clin Nuitr, 34 , pp.1752-1757, 1981; O'Dea, K., and AJ Sinclair, Increased propotion of arachidonic acid in plasma lipids after 2weeks on a diet of tropical seafood, 1982) And epidemiological studies on Japanese fishing villages (Hirai. A. et al., Eicosapentaenoic acid and platelet function in Japanese, Lancet, II. Pp . 1132-1133, 1980).

Hyperlipidemia drugs are used to lower levels of excess blood lipids, especially cholesterol and triglycerides. Major drugs used in lipid metabolism include statins, bile acid blockers and fibric acid derivatives, each of which acts as a different mechanism. The choice of therapeutic agents for hyperlipidemia may be a combination of these drugs, depending on the type of lipoproteins that have been increased, and they require long-term oral daily use. These drugs effectively lower cholesterol and blood lipid levels, but have the disadvantage of having side effects. Statins can cause nausea, headache, abdominal pain and diarrhea or constipation, which can cause muscle inflammation, and bile acid blockers can reduce the intestinal absorption of vitamins A, D, and K. And fibric acid derivatives are unsuitable drugs for kidney disease, liver disease or gallbladder disease. Therefore, there is a growing demand for the development of medicines and functional foods containing natural products in place of these preparations (Kook Seung-rae et al., Journal of Family Medicine, 18 (3) , pp.317-327, 1997).

The pathological model of experimental hyperlipidemia is divided into exogenous model and endogenous model. Exogenous hyperlipidemic condition models include hypercholesterolemia-induced models caused by high cholesterol dietary load, that is, hyperlipidemia by administration of vitamin D, cholesterol, olive oil, corn oil, etc., and endogenous hyperlipidemia models include fructose administration and WR. Models by administration of -1339 (Tripton WR-1339) (Ham IH et al., Kor. J, Herbology, 20 , pp. 45-52, 2005). Among them, poloxamer 407 is an anesthetic emulsifier (Lee HH et al., Kor. J. Anesthesiol, 40 , pp. 515-521, 2001), poorly soluble drug solubilizer (Choi JY et al., J. Kor. Pharm. Sci., 18 , pp. 240-241, 1988), skin ointments (Kim KK et al., J. Kor. Pharm. Sci., 28 , pp. 15-23, 1998) and the like. However, when administered in humans, lipids are increased, and in particular, triglycerides are increased, causing hyperlipidemia. Free fatty acid is produced in adipocytes for at least 24 hours after poloxamer injection (Nash VJ et al., Pharmacotherapy, 16 , pp.10-15, 1996), and the action of lipoprotein lipase (LPL) Decreases the rate of degradation of triglycerides that interfere with it (Stellato C. et al., Br. J. Anaesth., 67 , pp.751-758, 1991), and increases blood cholesterol and triglycerides in the liver. This is because it lowers the activity of hydroxy-3-methylglutaryl coenzyme A (HMG-CoA; 3-hydroxy-3-methylglutaryl CoA) (Wout GM et al., J. Paren. Sci. Technol., 46 , pp. 192-200, 1992).

On the other hand, squid is a mollusk belonging to the cephalopods Deungmok (十 脘 目), also known as Ogi (烏賊 魚). Squid is low in fat and carbohydrates and contains vitamin A, vitamin B1 and vitamin B2. There is a lot of calcium in the mineral, the protein content is about 17% of the total component. Squid proteins are known to contain amino acids such as taurine and histidine. In addition, squid nucleic acid is an important substance that regulates the body's cellular activity, has a pharmacological effect to prevent aging, and contains selenium, an essential mineral element in human cell metabolism.

Recently, a large amount of chemicals are being developed to treat hyperlipidemia, but their misuse may cause other side effects. As a countermeasure, there are active studies to find a cure from the natural foods we consume every day. It is done.

Therefore, the present inventors divided each part into three parts and the whole, ie, four parts (whole body, meat + fin, soy sauce, head + leg + bone) without discarding the squid, and the hyperlipidemic animal model. The present invention was completed by confirming that anti-lipidemia effect was shown by significantly reducing blood lipid content in.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of hyperlipidemia containing a squid fraction dry powder or extract as an active ingredient.

In addition, the present invention provides a health functional food for the prevention and improvement of hyperlipidemia containing the squid fraction dry powder or extract as an active ingredient.

A "squid fraction" as defined herein is one or more selected from the group consisting of the entire torso, meat, fins, soy, head, legs, bones, shells and eyes of the cuttlefish, preferably the entire torso, meat, fins, soy And from at least one selected site from the group consisting of head, legs and bones, more preferably from the entire torso or from the flesh and fins.

The extract as defined herein is a solvent selected from water, including purified water, a lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, preferably water, ethanol or a mixed solvent thereof, more preferably water and ethanol 50 to 99% Mixed solvents, even more preferably water and extracts soluble in 70-99% mixed solvents of ethanol.

Hereinafter, the present invention will be described in detail.

Squid fraction dry powder or extract of the present invention can be obtained by the following process.

Squid fraction dry powder of the present invention comprises the first step of washing and removing foreign substances and salts of squid captured in nearby waters such as the East Sea, South Sea, West Sea or the oceans such as the Pacific Ocean, the Atlantic Ocean; A second step of obtaining each fraction through a process of dividing the cuttlefish into whole body, meat, fin, soy sauce, bone, head, leg, skin, and eyes; A third step of performing each drying method of the fractions such as vacuum freeze drying method and sun drying method; Through the manufacturing method comprising a fourth step of grinding can be obtained squid fraction dry powder of the present invention.

In addition, the squid fraction extract of the present invention is a solvent selected from water containing purified water, lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, preferably water, ethanol or a mixed solvent thereof, more preferably water And 50 to 99% mixed solvent of ethanol, more preferably water and 70 to 99% mixed solvent of ethanol at 10 to 100 캜, preferably 15 to 50 캜 for 1 to 24 hours, preferably 3 to 10 hours. A first step of extracting hot or cold needles; The squid fraction extract of the present invention can be obtained through a manufacturing method comprising a second step of concentrating the same under reduced pressure and freeze-drying.

The present invention provides a pharmaceutical composition for the prevention and treatment of hyperlipidemia, which contains the dried squid fraction dry powder or extract obtained by the above method as an active ingredient.

The pharmaceutical composition for the prevention and treatment of hyperlipidemia containing the dried squid fraction dry powder or extract of the present invention as an active ingredient, comprises 0.1 to 50% by weight of the dry powder or extract based on the total weight of the composition.

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

The compositions of the present invention can be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral formulations, external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods. Carriers, excipients and diluents that may be included in the composition comprising the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations may include at least one excipient such as starch, calcium carbonate, sucrose in the extract. Or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium styrate 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. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. 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 composition of the present invention is preferably administered at 0.1 to 100 mg / kg per day. 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 can be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.

In another aspect, the present invention provides a health functional food for the prevention and improvement of hyperlipidemia containing the squid fraction dry powder or extract obtained by the above manufacturing process as an active ingredient.

The composition comprising the dry powder or extract of the present invention may be used in various ways, such as drugs, foods and beverages for the prevention and improvement of hyperlipidemia. Foods to which the dry powder or extract of the present invention may be added include, for example, various foods, beverages, gums, teas, vitamin complexes, health supplements, and the like, which are powders, granules, tablets, capsules, or beverages. Can be used as

The amount of the dry powder or extract in the food or beverage of the present invention may generally be added to 0.01-15% by weight of the total food weight of the health food composition of the present invention, the health beverage composition is 0.02 to 10 g based on 100 ml Preferably, it can be added in the ratio of 0.3-1 g.

The health beverage composition of the present invention contains the dried squid fraction dry powder or extract as an essential ingredient in the indicated ratio, and there are no particular limitations on the liquid component. It may contain. 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 mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, 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 present invention relates to a composition for the prevention and treatment of hyperlipidemia comprising a dried squid fraction dry powder or extract as an active ingredient. Specifically, the dried squid fraction dried powder or extract of the present invention significantly increases the blood lipid content of an animal model of hyperlipidemia. By reducing the anti-hyperlipidemic effect, the composition can be usefully used as a pharmaceutical composition or health functional food for the prevention and treatment of hyperlipidemia.

Hereinafter, the present invention will be described in detail by the following Examples, Reference Examples and Experimental Examples.

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

Example 1 Preparation of Sample

1-1. Preparation of Squid Fraction Dry Powder

Squid was 25.2 ± 0.7cm in length and 359.5 ± 41.3g in weight and was caught on October 23, 2007 on the east coast of Korea. After thawing the frozen squid, the foreign body and salt are washed and removed, and then divided into four parts each of the whole body, meat + fin, soy sauce, head + leg + bone, and then vacuum-dried for 48 hours at -80 ° C. (Vaccum Freeze Dryer, PVIFD30A, Korea Ilsan Co., Ltd.), and crushed into 50 mesh using a crusher (Hanil, HMF-1100) to cut the whole body of squid, meat + fins, soy, and head + legs + bones. 100g, 50g, 11.4g and 38.7g of dried powder were obtained and used in the following experimental example (hereinafter, squid whole body dry powder 'S-1', meat + fin dry powder 'S-2', soy sauce drying The powder is called 'S-3' and the hair + legs + bone dry powder is called 'S-4').

1-2. Preparation of Squid Fraction Extract

200 g of 97% ethanol was added to 100 g, 50 g, 11.4 g, and 38.7 g of S-1, S-2, S-3, and S-4 obtained in Example 1-1, respectively, three times at 20 ° C. for 5 hours. Extracted. The resultant was concentrated under reduced pressure and freeze-dried (Vaccum Freeze Dryer, PVIFD30A, Korea Ilsan) to obtain 18.3 g, 18.6 g, 4.9 g and 14.9 g of squid whole body, meat + fins, soy sauce and head + leg + bones, respectively. (Hereinafter, squid whole body extract 'SE-1', meat + fin extract 'SE-2', soy sauce extract 'SE-3', head + leg + bone extract 'SE-4').

Reference Example 1. Preparation of Experimental Animals and Experimental Diet

Healthy animals that have been adapted for 1 week after 200 ± 5g SPF Sprague Dawley (SD) rats and 200 ± 5g ICR male mice were purchased from Daehan Biolink. Bay was used for the experiment. The breeding environment of this experiment was used in experimental animal breeding room (TECNIPLAST, Italy) of Kyungsung University College of Pharmacy with temperature 22 ± 3 ℃, relative humidity 50 ± 10%, lighting time 12 hours (07: 00 ~ 19: 00). Solid feed (Samyang feed, Daejeon) and tap water (negative) were ingested freely. 24 hours before the start of the experiment only watered and fasted. 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.

The experimental animals were divided into 10 groups of 5 animals per group, the control group fed the normal feed, the negative control group administered with poloxamer-407 to cause hyperlipidemia, S-1, S-2, S-3 And S-4 administration test groups. S-1, S-2, S-3 and S-4 were suspended in 10% Tween 80 and 100 and 200 mg / kg of the animals were ingested for 4 weeks once a day using oral zones. .

Experimental Example 1. Measurement of Triglyceride Content Inhibition Effect in Hyperlipidemic Animals Induced by Poloxamer-407

S-1 and S-2 obtained in Example 1-1 according to the method of Wout et al. (Wout et al., J. Paren. Sci. & Technol, 46 , pp.192-200, 1992) on the day of the experiment . Poloxamer-407 (300 mg / kg), known as a substance that causes hypertriglyceridemia at the last dose of S-3 and S-4, was physiologically treated in an ice bath. dissolved in saline solution was measured in the blood triglyceride content of queries to administration and blood sampling after 48 hours into the abdominal cavity (the outer yiyeonsil 3, the effect of the extract of algae in water rail on lipid metabolism, Biochemical Journal, 35 (2), pp.143- 146, 2004).

Experiments were conducted as described below by applying the method described in the literature in order to measure the blood triglyceride content of each fraction of the squid (McGowan, MW et al., A peroxidase-coupled method for the colorimetric determination of serum triglycerides. Clin Chem. 29 , pp538-542, 1983).

Experiments were carried out using kits prepared according to the method of McGowan et al. (AM 157S-K, Asan). In other words, the enzyme reagent (containing lipoprotein lipase 10800U, glycerol kinase 5.4U, peroxidase 135000U, L-α-glycero phosphooxidase 160U) was dissolved in an enzyme reagent [N, N-bis (2-hydroxyethyl) -2-aminomethane sulfonic acid dissolved in 0.427 g / dl], 3.0 ml of the enzyme reagent prepared in 20 µl of the sample was added and incubated at 37 ° C. for 10 minutes to measure absorbance at a wavelength of 550 nm. According to the standard calibration curve, the blood triglyceride content is shown in Table 1 below in mg / dl.

As shown in Table 1, the blood triglyceride content of the control group was 1040.02 ± 159.25 mg / dL, which is about 10 times higher than the 113.20 ± 25.4 mg / dL of the normal group, and the content of triglyceride in the blood was significantly increased by poloxamer-407. Could confirm. When different concentrations of 100 and 200 mg / kg of S-1 (squid whole body fraction), S-2 (squid meat + fin fraction) and S-4 (squid head + leg + bone fraction) were administered, The levels of neutral lipids in the blood were 916.27 ± 79.82 mg / dL, 858.56 ± 37.84 mg / dL, 889.82 ± 73.55 mg / dL, 821.53 ± 36.61 mg / dL, and 900.85 ± 66.40 mg / dL and 875.88 ± 95.36 mg / dL, respectively. By confirming, the increased content of triglycerides in the blood due to poloxamer-407 treatment was S-1 (squid whole body fraction), S-2 (squid meat + fin fraction) and S-4 (squid head + leg + bone fraction). It can be seen that by the administration of all fractions showed a significant inhibitory effect with increasing concentration. In particular, the S-2 (squid meat + fin fraction) was found to have the best inhibitory effect of blood triglyceride content in a concentration-dependent manner. On the contrary, in the case of S-3 (squid liver fraction), it was confirmed that the inhibition rate of the triglyceride content increased by poloxamer-407 treatment was not only the smallest, but also showed no significance according to the concentration.

Therefore, the experimental groups to which each of the four squid fraction dry powders were administered were treated with poloxamer-407 (poloxamer-407), which significantly increased blood triglyceride content in S-1, S-2, S-3 and The effect of inhibiting significantly (p <0.05) was confirmed in S-4, and in the case of S-1, S-2, and S-4 except S-3, the higher the dose concentration, the more neutral lipid content was suppressed. It was confirmed that the superiority.

Treated group Dose
(mg / kg) Triglyceride mg / dl Control 113.20 ± 25.4 ^d Negative Control (Poloxamer-407) 1040.02 ± 159.25 ^a S-1
(Whole body) 100 916.27 ± 79.82 ^bc 200 858.56 ± 37.84 ^bc S-2
(6 + fins) 100 889.82 ± 73.55 ^bc 200 821.53 ± 36.61 ^c S-3
(Soy sauce) 100 924.93 ± 71.12 ^abc 200 959.23 ± 120.91 ^ab S-4
(Head + leg + bone) 100 900.85 ± 66.40 ^bc 200 875.88 ± 95.36 ^bc Mean ± Standard deviation. Values marked with the same letter are not significantly different from each other (p <0.05, Duncan's multiple range test)

It describes a formulation example of a composition comprising a dry powder or an extract of the present invention, the present invention is not intended to limit it, but is intended to explain in detail only.

Formulation Example 1 Preparation of Powder

S-1 20 mg

Lactose 100 mg

Talc 10 mg

The above ingredients are mixed and filled in an airtight cloth to prepare a powder.

Formulation Example 2 Preparation of Tablet

S-2 10 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets are usually prepared by tableting according to the method for preparing tablets.

Formulation Example 3 Preparation of Capsule

S-3 10 mg

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 0.2 mg

According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.

Formulation Example 4 Preparation of Injection

S-4 10 mg

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

_{Na 2 HPO 4 · 12H 2 O} 26 mg

It is usually prepared in the above ingredient content per ampoules (2 ml) according to the preparation method of the injection.

Formulation Example 5 Preparation of Liquid

S-1 20 mg

10 g of isomerized sugar

5 g of mannitol

Purified Water Proper Amount

Normally, each component is added to the purified water to dissolve according to the preparation method of the liquid solution, lemon flavor is added, the above ingredients are mixed, purified water is added, the whole is adjusted to 100 ml by the addition of purified water, and then filled into a brown bottle and sterilized. To prepare a liquid solution.

Formulation Example 6 Preparation of Health Functional Food

S-2 1000 mg

Vitamin mixture proper amount

70 μg of Vitamin A Acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

0.2 μg of vitamin B12

Vitamin C 10 mg

10 μg biotin

Nicotinamide 1.7 mg

50 μg folic acid

Calcium Pantothenate 0.5 mg

Mineral mixture

Ferrous Sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

15 mg potassium monophosphate

Dicalcium 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 mixtures is a composition that is relatively suitable for the health functional food, the composition is mixed in a preferred embodiment, but the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health functional food manufacturing method. Then, the granules may be prepared and used for preparing the nutraceutical composition according to a conventional method.

Formulation Example 7 Preparation of Healthy Drink

S-3 1000 mg

Citric acid 1000 mg

100 g oligosaccharides

Plum concentrate 2 g

1 g of taurine

900 ml of purified water whole

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

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 (6)

A pharmaceutical composition for the prevention and treatment of hyperlipidemia, which contains dried squid meat and fin fractions as an active ingredient. delete delete delete Health functional food for the prevention and improvement of hyperlipidemia containing squid meat and fin fraction dry powder as an active ingredient. delete