WO2021045554A1 - Pharmaceutical composition comprising processed fish product and/or processed soybean product as active ingredient - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating at least one disease selected from hyperlipidemia, dyslipidemia, hypercholesterolemia, hypertriglyceridemia, hypertension, arteriosclerosis, coronary heart disease, stroke, fatty liver, thrombosis, and obesity, the pharmaceutical composition comprising active ingredients contained in a processed fish product and/or processed soybean product.

Description

Pharmaceutical composition comprising processed fish and/or processed soybean as an active ingredient

The present invention relates to a pharmaceutical composition comprising an anchovy processed product and/or a soybean processed product as an active ingredient, and more specifically, a fish processed product and/or a soybean processed product containing the active ingredient, hyperlipidemia, dyslipidemia, high cholesterol It relates to a pharmaceutical composition for the prevention or treatment of one or more diseases selected from bloodemia, hypertriglyceridemia, hypertension, arteriosclerosis, coronary heart disease, stroke, fatty liver, thrombosis and obesity.

In modern society, metabolic diseases are increasing due to a convenient living environment due to rapid automation, excessive nutritional intake due to an increase in processed pharmacies and eating out, and a decrease in physical activity.

On the other hand, blood circulation means that blood moves to each part of the body through blood vessels, and blood supplies oxygen and nutrients to each tissue of the body, and removes waste products created by cells.

In addition, it carries hormones necessary for our body, protects cells from external harmful substances, maintains proper body temperature, and maintains homeostasis in the body, such as hemostasis.

Therefore, smooth blood flow is very important to maintain body functions, and it is known that the incidence of cerebrovascular diseases such as arteriosclerosis and stroke increases when such blood flow is impaired.

The main factors affecting blood flow include chronic diseases such as high blood pressure and diabetes, diet, lifestyle, and genetic factors. As the standard of living increases and the diet becomes westernized, the incidence of cerebral cardiovascular diseases related to blood circulation disorders increases. This is causing socioeconomic problems.

On the other hand, hyperlipidemia refers to a condition in which lipids such as free cholesterol, cholesterol esters, phospholipids, and triglycerides are abnormally increased in the blood.

Hyperlipidemia usually does not show symptoms by itself, but if there is a lot of fat in the blood, it sticks to the walls of blood vessels and causes atherosclerosis, which can lead to coronary heart disease, cerebrovascular disease, and peripheral blood vessel obstruction. Yes (Non-Patent Document 1).

In addition, excessive fat components as described above are accumulated in the liver tissue, which may cause fatty liver.

In the above, fatty liver refers to a state in which the ratio of fat to the weight of the liver exceeds 5%, and may be caused not only by intake of excessive fat components but also by intake of alcohol.

On the other hand, as a method of reducing blood lipid concentration, diet, exercise, and drug therapy are recommended to suppress the intake of pharmaceuticals containing a lot of cholesterol or saturated fatty acids and reduce caloric intake.

However, diet or exercise therapy is difficult to strict management and implementation, and its effectiveness is often limited.

Lipid concentration reducing agents developed to date include bile acid binding resins, HMG-CoA reductase inhibitors, drugs that lower cholesterol such as neomycin, probucol, and fibric acid derivatives. Drugs that lower triglyceride content such as nicotinic acid have been developed and are being used as therapeutic agents.

However, these drugs have side effects such as hepatotoxicity, gastrointestinal disorders, and carcinogenicity.Therefore, studies on natural products that can prevent or treat hyperlipidemia, arteriosclerosis and fatty liver by reducing excessive lipid concentration in the blood are safe for the human body without side effects. It's going on.

For example, it has been reported that the methanol extract of tissue cultured wild ginseng has the activity of lowering total cholesterol and LDL-cholesterol levels and increasing HDL-cholesterol levels in hyperlipidemic rats induced by a high fat diet (Non-Patent Document 2). , It has been reported that the petroleum ether extract of ginseng and panaxydol, a component contained in the extract, have the activity of inhibiting cholesterol absorption (Patent Document 1), and the cholesterol-lowering effect of shiitake, ganoderma lucidum, and oyster mushroom powders Has been reported (Patent Document 2).

Under this background, the present inventors have made intensive research efforts to develop a pharmaceutical composition having an effect of improving blood circulation, improving blood triglycerides, improving blood cholesterol, and anti-obesity. As a result, fish processed products and/or soybean processed products improve blood circulation, blood triglycerides. It was confirmed that the improvement, blood cholesterol improvement, and anti-obesity effect were shown, and the present invention was completed.

{Prior technical literature}

{Patent Literature}

(Patent Document 1) Korean Registered Patent Publication No. 10-1691605

(Patent Document 2) Republic of Korea Patent Publication No. 10-2013-0107659

{Non-patent literature}

(Non-Patent Document 1) Circulation 92, 657-671, (1995)

(Non-Patent Document 2) Kor. J. Pharmacogn. 34(2): 179-184 (2003)

The present invention was invented to solve the above problems, and an object of the present invention is to improve blood circulation, improve blood triglycerides, improve blood cholesterol, and a pharmaceutical composition comprising a processed fish and/or a processed soybean product having an anti-obesity effect as an active ingredient Is to provide.

Another object of the present invention is one or more diseases selected from hyperlipidemia, dyslipidemia, hypercholesterolemia, hypertriglyceridemia, hypertension, arteriosclerosis, coronary heart disease, stroke, fatty liver, thrombosis and obesity comprising the active ingredient. It is to provide a pharmaceutical composition for prophylaxis or treatment.

In order to achieve the above object, the present invention comprises as an active ingredient at least one selected from processed fish and processed soybeans, hyperlipidemia, dyslipidemia, hypercholesterolemia, hypertriglyceridemia, hypertension, arteriosclerosis, It provides a pharmaceutical composition for preventing or treating at least one disease selected from coronary heart disease, stroke, fatty liver, thrombosis and obesity.

The pharmaceutical composition comprising as an active ingredient at least one selected from fish processed products and soybean processed products according to the present invention exhibits improved blood circulation, improved blood triglycerides, improved blood cholesterol, and anti-obesity effects.

Therefore, the present invention is for preventing or treating cardiovascular diseases such as hyperlipidemia, dyslipidemia, hypercholesterolemia, hypertriglyceridemia, hypertension, arteriosclerosis, coronary heart disease, stroke, thrombosis, and one or more diseases selected from fatty liver and obesity. It has a very useful effect as a pharmaceutical composition.

In addition, the pharmaceutical composition according to the present invention can exhibit the above-described effects without side effects such as hepatotoxicity, gastrointestinal disorders and carcinogenicity by using natural fish resources widely used as food, and various capsules, tablets, solutions, suspensions or By exerting the above-described effect manufactured as an injection or the like, there is an excellent effect that can increase national health and reduce social and economic expenditures resulting therefrom.

1 shows the results of evaluating the blood coagulation inhibitory activity related to the improvement of blood circulation of the pharmaceutical composition according to the present invention.

As for terms used in the present invention, general terms that are currently widely used are selected, but in certain cases, some terms are arbitrarily selected by the applicant. In this case, the meanings described or used in the specific contents for carrying out the invention are not just the names of terms. The meaning should be grasped in consideration of.

The present invention comprises as an active ingredient at least one selected from fish, particularly fish processed products of herring and soybean products, as an active ingredient, hyperlipidemia, dyslipidemia, hypercholesterolemia, hypertriglyceridemia, hypertension, arteriosclerosis, coronary heart disease It relates to a pharmaceutical composition for preventing or treating one or more diseases selected from stroke, fatty liver, thrombosis and obesity.

The processed fish included in the pharmaceutical composition of the present invention is preferably herring fish, more preferably sardine family fish, and most preferably anchovy processed products may be used. Such processed fish may be, for example, one or more selected from dried fish, semi-dried fish dried to a certain moisture content or less, pulverized raw fish, fish meal meju containing fish, and fish sauce.

According to a preferred embodiment of the present invention, the processed fish may be more preferably at least one selected from dried fish, semi-dried fish dried to a certain moisture content or less, pulverized raw fish, fish meal meju and fish sauce. Applicable to fish or fish sauce used herein is meant to include fish and shellfish including fish, shellfish, and crustaceans, preferably, for example, herring fish, more preferably sardines, and most preferably anchovies.

According to a preferred embodiment of the present invention, preferably, the processed fish and/or soybean may be fermented fermented products.

The dried fish that may be included in the pharmaceutical composition of the present invention generally refers to general dried fish including natural drying, and the semi-dried fish may be semi-dried to a moisture content of 55% or less, and the fish meal meju During molding, it may contain not more than 20% by weight, preferably not more than 0.01% to 20% by weight of fishmeal based on the total weight of the meju.

The fish meal contained in the meju may include herring fish, preferably sardine family fish, and most preferably powder of anchovy, such as anchovy, anchovy, herring, canary, saury, gulbi, blacktail, and horse mackerel. Powder derived from one or more fish species selected from, preferably anchovy powder may be used.

It is assumed that the fish sauce of the present invention that can be included in the pharmaceutical composition of the present invention may contain shellfish in addition to simple fish. That is, the fish sauce as the processed fish product of the present invention includes those to which the fish sauce is applied substantially.

The fish sauce may be more precisely referred to as a fish sauce fish sauce, wherein the fish and shellfish are preferably herring order, more specifically, sardine family, and most preferably, anchovy fish sauce, such as anchovy, octopus, squid, One or more fish sauces selected from sardines, blacktail, herring, herring, mackerel, mackerel, smelt, canary, yellowtail, skate, tuna, horse mackerel, saury, konjac, badorachi, gulbi, pollock, yangmiri, mussels, clams, shrimp, and blue crab It may be, and most preferably, anchovy fish sauce or gulbi fish sauce may be used.

At this time, the processed fish may be prepared and prepared through various methods, but according to an embodiment of the present invention, it may be prepared through the following method.

The method of manufacturing the semi-dried fish product includes preparing raw fish.

At this time, as the raw fish, at least one selected from dried fish, semi-dried fish dried to a certain moisture content, crushed raw fish, fish meal meju and fish sauce is used, and the fish used as the prepared raw fish is brine And washing with.

Next, the pharmaceutical composition using the processed fish according to the embodiments of the present invention as an active ingredient may include removing salt water from the washed raw fish and drying it.

At this time, the step of removing the brine may be performed through various methods, but in embodiments of the present invention, the brine contained in the washed raw fish is removed using a network such as a centrifuge, a tunnel type vibrator, and a stationary type. do.

At this time, the moisture content of the raw fish from which the brine has been removed is maintained at 60-80%, preferably 70-75%. Such fish can be cut, ground or crushed by a conventional method to be used as raw fish or dried.

On the other hand, the drying of the raw fish from which the salt water has been removed is semi-drying so that the moisture content of the raw fish is within 55% by using any one method selected from methods including hot air, cold air, pre-heat drying, and natural drying. I can.

The reason for semi-drying the raw fish is to increase the concentration of protein contained in the raw fish by semi-drying the raw fish.

On the other hand, the pharmaceutical composition comprising the processed fish according to the embodiments of the present invention as an active ingredient may further include processing the semi-dried raw fish, at this time referred to as processing the semi-dried raw fish. Crushing semi-dried raw fish to a certain particle size, liquefying or using a specific solvent to improve blood circulation contained in the raw fish, improve blood triglycerides, improve blood cholesterol, and extract active ingredients related to anti-obesity, etc. It may include.

The soybean processed product included in the pharmaceutical composition of the present invention may be at least one selected from fermented soybeans, meju, miso, and soy sauce, but is not limited thereto. According to a preferred embodiment of the present invention, preferably, the soybean processed product may be fermented fermented product.

Beans applied to the processed soybeans that may be included in the pharmaceutical composition of the present invention include, for example, one or more selected from kidney beans, mung beans, soybeans, eastern beans, peanuts, lentils, lima beans, peas, etc., preferably It may be soybean, but is not limited thereto.

The soybean is rich in high-quality vegetable protein and fat enough to be called'meat of the field', and is used as a raw material for soy sauce and soybean paste that we encounter every day, and as a source of essential foods such as tofu and bean sprouts, meat and There are a lot of high-quality proteins that are comparable to that, and isoflavones help calcium absorption to help prevent osteoporosis, and saponins act as antioxidants. In addition, there is a relatively advantageous aspect of securing raw materials.

The fermented beans that may be included in the pharmaceutical composition of the present invention are, for example, soaked in water for 1 to 10 hours, preferably 2 to 5 hours, and then boiled, and then boiled at 35 to 50°C, preferably at 40 to 45. It can be obtained by fermenting for 1 to 5 days at °C, preferably for 1 to 3 days, but is not limited thereto.

The meju, which may be included in the pharmaceutical composition of the present invention, refers to used as a raw material for soy sauce, soybean paste, and red pepper paste as a raw material for boiling and pounding soybeans and then floating and drying soybeans. , Bean-al meju, noodle-type meju, and the like, but are not limited thereto.

The fish meal meju that may be included in the pharmaceutical composition of the present invention can be applied as a processed fish oil, but may be classified as a processed soybean product. Such fish meal meju may contain 20% by weight or less, preferably 0.01% to 20% by weight or less of fishmeal based on the total weight of the meju when forming the meju.

The fish meal may be powder derived from one or more fish species selected from the group consisting of anchovy, anchovy, herring, canary, saury, blackfish and horse mackerel, preferably anchovy powder, but is not limited thereto.

The fish meal may be prepared through raw material selection, boiling, pressing, oil-water separation, drying, and pulverization, but is not limited thereto.

As an example of the present invention, the boiling process of soybeans is an important process and becomes a pretreatment of the oil-water separation process of disinfecting products and separating water-soluble and fat-soluble proteins. After the boiling process is finished, it is separated again by a compression process, the remaining solids undergo a solid compression process, and the water-soluble part undergoes a purification process through centrifugation.

After the refining process is finished, it may be pulverized to a predetermined size through a drying process, but is not limited thereto.

The soybean paste that may be included in the pharmaceutical composition of the present invention includes soybean paste made from ingredients left after scooping the soybean paste by soaking it with meju. It may include, but is not limited to, opening, flour paste, barley paste, and the like.

The soy sauce, which may be included in the pharmaceutical composition of the present invention, is a soy sauce, preferably soybeans, soybeans, preferably soybeans, soy sauce, soy sauce, soy sauce, soy sauce, soy sauce, and enzymes. It may include improved soy sauce such as decomposed soy sauce and mixed soy sauce, but is not limited thereto.

The soy sauce according to an embodiment of the present invention may be prepared by using pre-prepared meju and sea salt, optionally adding fish sauce, and stirring the soy sauce, but is not limited thereto.

At this time, the meju can be prepared by steaming the beans, cooling the steamed beans to a certain temperature or less, and inoculating a specific strain cultured on the steamed beans.

At this time, the strain can be used as well as various strains, in the present invention Bacillus bacteria, preferably Bacillus subtilis (Bacillus subtilis) or Bacillus velezensis (Bacillus velezensis) can be inoculated, but limited thereto. It does not become.

Thereafter, the beans inoculated with the Bacillus bacteria are molded into a general meju shape using a molding machine, and then fermented to prepare them.

Meanwhile, the soy sauce may be fermented under certain conditions and filtered after stirring the meju, sea salt, and fish sauce.

Thereafter, after adding specific lactic acid bacteria to the filtered mixture, fermentation and sterilization are performed again to prepare the soy sauce.

At this time, since it is sufficient to use what is widely known in the art as the lactic acid bacteria, specific types thereof will be omitted.

The pharmaceutical composition of the present invention may contain 99% by weight or less, preferably 0.01 to 99% by weight, more preferably 0.1 to 50% by weight, based on the total weight of the fish product and/or soybean product, It is not limited thereto.

The pharmaceutical composition of the present invention may be provided in any suitable form without particular limitation, according to a predetermined purpose. For example, it may be provided in a form suitable for administration to a subject in need thereof by oral administration, transdermal administration, or injection administration (including intravenous injection, intramuscular injection, subcutaneous injection, etc.), but is limited thereto. no.

As the form for oral administration, the pharmaceutical composition of the present invention may contain any pharmaceutically acceptable carrier that will not negatively affect the desired effect of the active ingredient (ie, protein fermentation product). Examples of such carriers include water, saline, dextrose, glycerol, ethanol or analogs thereof, oils (e.g. olive oil, castor oil, cottonseed oil, peanut oil, corn oil, germ oil), starch, polyethylene glycol, kaolinite, bentonite, citric acid. Sodium, gelatin, agar, carboxymethylcellulose, gum arabic, algin and salts thereof, glyceryl monostearate, calcium stearate, and combinations of one or more thereof, but are not limited thereto.

The pharmaceutical composition of the present invention may be in any suitable form for oral administration by any suitable method, such as tablets (e.g., sugar-coated tablets), pills, capsules, granules, powders, flow extracts, solutions, syrups. , May be provided in the form of a suspension, tincture, etc.

As a form for transdermal administration, any pharmaceutically acceptable carrier that will not negatively affect the desired effect of the active ingredient may be included. Examples of such a carrier include water, mineral oil, and hyaluronic acid, but are not limited thereto.

The pharmaceutical composition of the present invention may be provided in any suitable form for transdermal administration by any suitable method, such as a patch (eg, a microneedle patch), but is not limited thereto.

The pharmaceutical composition of the present invention is in the form of an injection or intravenous administration device suitable for the injection administration, isotonic solution, salt-buffered saline (e.g., phosphate buffered saline or citrate buffered saline), hydrotropic agent, emulsifier, 5 % Sugar solution and one or more ingredients such as intravenous infusion, emulsified intravenous infusion, powder for injection, suspension for injection or other carriers for providing pharmaceutical compositions as powder suspension for injection.

The pharmaceutical composition of the present invention may be administered at various administration frequencies, for example, once a day, several times a day, or once every several days, depending on the needs of the subject, age, weight, and health condition. In addition, the concentration of the protein fermentation product in the pharmaceutical composition may be adjusted according to actual application requirements.

In addition, the pharmaceutical composition may optionally further enhance the effect, or additionally one or more other active ingredients (e.g., antihypertensive agents, lipid-lowering agents, hypoglycemic agents, etc.) in order to improve the application flexibility and applicability of the provided formulation. It may be included, or may be used in combination with a drug containing one or more other active ingredients, but is not limited thereto.

The pharmaceutical composition of the present invention may further include a carrier, examples of the carrier include excipients, diluents, adjuvants, stabilizers, absorption delaying agents, disintegrants, lubricants, hydrotropic agents, emulsifiers, antioxidants, adhesives, and binders. , A tackifier, a dispersant, a suspending agent, a lubricant, a desiccant, and the like, but are not limited thereto.

In the pharmaceutical composition of the present invention, the active ingredient contained in the processed fish or soybeans as the active ingredient, such as processed fish or soybean extract, is administered in the range of 1 mg/kg to 100 mg/kg per day based on an adult body weight of 60 kg. It can be adjusted within, preferably 10mg / kg.

In addition, the type of disease, the severity of the disease, the content of active ingredients and other ingredients contained in the composition, the type of formulation, and the age, weight, general health condition, sex and diet of the patient, administration time, administration route and minutes of the composition. It can be adjusted according to a variety of factors, including the rate, duration of treatment, and drugs used simultaneously.

The pharmaceutical composition of the present invention may exhibit at least one activity selected from improvement of blood circulation, inhibition of blood triglycerides, inhibition of blood cholesterol, and inhibition of angiotensin converting enzyme.

On the other hand, the pharmaceutical composition of the present invention has the effect of improving blood circulation as described above, and the effect of improving the blood circulation is that the active ingredient of the anchovy processed product and/or soybean processed product of the present invention inhibits the formation of blood clots in the blood or generated blood clots. By decomposing or suppressing the contraction of the blood vessel wall, the effect of improving blood circulation can be exhibited.

In addition, the active ingredient of the processed fish and/or the processed soybean may exhibit an effect of improving blood triglycerides by inhibiting the differentiation of adipocytes.

In addition, the active ingredient of the processed fish and/or the processed soybean may reduce the total cholesterol content in the blood.

On the other hand, according to an embodiment of the present invention, in order to confirm the effect of improving blood circulation of the pharmaceutical composition, evaluation of platelet aggregation inhibition, evaluation of blood coagulation inhibition, measurement of procoagulant activity in red blood cells, and shear stress Platelet and red blood cell activation induced by the evaluation was performed, and vasoconstriction-relaxation function evaluation was performed to confirm the effect of improving blood circulation through the inhibition of vasoconstriction of the present invention.

In addition, arterial thrombosis was evaluated in parallel, and the fibrin plate method was modified to evaluate thrombus resolution, and a commercially available control plasma (MD Pacific Technology Co. Ltd, Huayuan Industrial Area, China) was used as plasma. Thrombin time, prothrombin time and AP time were measured.

As a result of evaluation and measurement, all of the pharmaceutical compositions containing the processed fish according to the embodiments of the present invention as an active ingredient showed excellent blood circulation improvement effects.

On the other hand, in order to improve blood triglycerides or to confirm the anti-obesity effect of the pharmaceutical composition according to the present invention, various in-vivo tests were performed to confirm the inhibition of triglyceride cell differentiation. In the step of differentiating from preadipocytes to adipocytes, in order to confirm whether the pharmaceutical composition of the present invention is effective in reducing adipocytes, a test was performed to measure the amount of produced adipocytes, and all results of the results were excellent in improving triglycerides. Appeared to be.

In addition, tributyrin (Tributyrin) tributyrin (Tributyrin) as a result of performing the triglyceride inhibitory ability analysis, it was confirmed that the pharmaceutical composition of the present invention exhibits a high triglyceride inhibitory ability.

In addition, in order to confirm the effect of improving blood cholesterol of the pharmaceutical composition according to the present invention, an in-vivo test was performed in which animals ingested the pharmaceutical composition of the present invention, normal animals, and animals ingested a high cholesterol diet as controls. As a result of comparing total cholesterol content in serum and HDL/LDL/VLDL cholesterol content in serum, both showed excellent cholesterol improvement effect.

In particular, as a result of measuring the content of lipid peroxide in parallel, it was confirmed that the pharmaceutical composition of the present invention has an excellent effect in improving cholesterol.

As a result, the pharmaceutical composition according to the present invention has improved blood circulation, improved blood triglycerides, improved blood cholesterol, and anti-obesity through the above-described technical configurations, and based on these mechanisms of action, hyperlipidemia, dyslipidemia, hypercholesterolemia, hyperlipidemia It can be applied as a pharmaceutical composition effective in preventing or treating one or more diseases selected from triglyceridemia, hypertension, arteriosclerosis, coronary heart disease, stroke, fatty liver, thrombosis and obesity.

In particular, the composition of the present invention can exhibit the above-described effects without side effects such as liver toxicity, gastrointestinal disorders and carcinogenicity by using natural fish resources, and is prepared in various capsules, tablets, liquids, suspensions or injections, etc. It has an excellent effect that can increase national health and reduce social and economic expenditures.

As described above, the present invention has been described with reference to a preferred embodiment, but it is not limited to the above-described embodiment, and within the scope of the technical spirit of the present invention, by those of ordinary skill in the art. It will be said that various changes and modifications are possible.

<Example 1> Blood circulation improvement effect

(1) ACE inhibitory activity evaluation

The results of measuring the ACE inhibitory activity of the pharmaceutical composition of the present invention are shown in Table 1 below.

Angiotensin converting enzyme (Kinase peptidyldipeptide hydrolase, EC 34151) cleaves the C-terminal dipeptide (His-Leu) of angiotensin, an inactive decapeptide, and strong blood pressure by actions such as contraction of blood vessel wall smooth muscle. It is known that it plays a role in raising blood pressure by inactivating bradykinin, a nonapeptide having a strong vasodilating action, while producing angiotensin, an octapeptide that exhibits synergistic action.

In the mechanism of hypertension, the renin-angiotensin system plays a very important role in blood pressure regulation.

In particular, ACE is an enzyme involved in the final step of synthesizing angiotensin, an octapeptide that acts as a vasoconstrictor by hydrolyzing the C-terminal dipeptide from the decapeptide angiotensin produced by renin.

The generated angiotensin promotes the secretion of aldosterone in the adrenal cortex, inhibits the excretion of water and sodium, and suppresses bradykinin, a nonapeptide that has a vasodilating effect, and consequently increases blood pressure.

Therefore, the ACE inhibitory action prevents blood vessel constriction and water retention in the body, thereby lowering blood pressure and improving blood circulation.

The ACE inhibitory activity was calculated according to Equation 1 below.

[Equation 1]

In Equation 1, A is the absorbance of the group to which the pharmaceutical composition is added, B is the absorbance of the group to which the pharmaceutical composition is not added, and A and B are values excluding the absorbance of the control group.

sample	IC 50 (㎍/mL)
Developed Product 1	392.15±2.20
Developed Product 2	556.21±3.38
Developed Product 3	713.58±2.26
Control	1003.35±3.04
IC 50 (Half maximal inhibitory concentration): ACE inhibition value by sample

* The above values are expressed as mean±standard deviation (n=3).

_{Referring to Table 1 above, IC 50} of the developed product 1 (salted anchovy + soy sauce), developed product 2 (salted anchovy), and developed product 3 (soy sauce using general meju) of the present invention is applied to the control to which the developed product is not added. Compared to this, it showed a significantly lower value, and thus, it was found that the aforementioned effect of preventing blood vessel contraction and improving blood circulation accordingly was excellent.

(2) Evaluation of vasoconstriction relaxation function

In this regard, the descending thoracic aorta of the rat was excised to evaluate the contraction/relaxation response of the blood vessel by the developed product according to the present invention in an organ bath system.

At this time, phenylephrine is used for the contraction of blood vessels, and the degree of contraction caused by the cumulative dose is determined, and the relaxation of the blood vessels is phenylephrine, which causes the same degree of contraction in the blood vessels of each treatment group. Thereafter, it was induced by additionally adding acetylcholine, and the result of relaxation was calculated as the relaxation rate for contraction of phenylephrine and compared with the control.

At this time, the control means a state in which the pharmaceutical composition according to the present invention is not added.

In this regard, referring to FIG. 1, it was confirmed that when the developed product (anchovy sauce + soy sauce) according to the present invention was added, blood vessel contraction was suppressed in a concentration-dependent manner compared to the control without the addition.

<Example 2> Blood triglyceride improvement effect

In order to measure blood triglycerides, a normal control group, a negative control group (hyperlipidemia induction group), Experimental Example 1 (hyperlipidemia induction + liver), Experimental Example 2 (hyperlipidemia induction + fish sauce) and experiment Blood of ICR mice by Example 3 (hyperlipidemia induction + (fish sauce + liver)) was centrifuged at 1,500 X g (Sorvall ^TM Legend ^TM Micro 17 Micro centrifuge, Thermo Scientific Inc., Waltham, MA, USA) to obtain plasma. Separated.

The blood cells and separated plasma were transferred to a sterilized tube and used to measure blood triglycerides.

The blood triglyceride was measured using a Triglyceride colorImetric assay kit (Cayman, Ann Arbor, MI, USA), and each absorbance was measured with a SpectraMax 340PC384 Microplate Reader (Molecular Devices, Sunnyvale, CA, USA). The results are shown in Table 2 below.

At this time, the induction of hyperlipidemia was performed by supplying a fixed amount of diet and drinking water having a 5-week-old ICR mouse (25±2g) / 45% fat content sufficiently, and each of the experimental groups was constant temperature (25±2°C) and humidity (50 ±5%) and negative/positive 12 hours conditions were maintained.

division	Triglyceride (mg/dL)
Normal control	90.18±4.22
Negative control	137.80±5.86
Laboratory Example 1	110.88±6.02
Laboratory example 2	102.50±5.24
Laboratory Example 3	88.69±4.62

Referring to Table 2, it can be seen that the samples of the laboratory examples 1 to 3 according to the present invention exhibit higher triglyceride inhibitory ability compared to the negative control group.

<Example 3> Blood cholesterol improvement effect

In order to measure blood cholesterol, a normal control group, a negative control group (hyperlipidemia induction group), Experimental Example 1 (hyperlipidemia induction + liver), Experimental Example 2 (hyperlipidemia induction + fish sauce), and experiments were conducted. ^{Plasma by centrifugation (Sorvall TM} Legend ^TM Micro 17 Micro centrifuge, Thermo Scientific Inc., Waltham, MA, USA) of ICR mouse blood by Example 3 (hyperlipidemia induction + developed product (fish sauce + liver)) at 1,500 X g Separated.

The blood cells and separated plasma were transferred to a sterilized tube and used to measure blood cholesterol.

The blood cholesterol was measured using an EnzyChrom HDL and LDL/VLDL assay kit (Bioassay system, Hayward, CA, USA), and each absorbance was SpectraMax 340PC384 Microplate Reader (Molecular Devices, Sunnyvale, CA, USA). The results measured by are shown in Table 3 below.

At this time, the induction of hyperlipidemia was performed by supplying a fixed amount of diet and drinking water having a 5-week-old ICR mouse (25±2g) / 45% fat content sufficiently, and each of the experimental groups was constant temperature (25±2°C) and humidity (50 ±5%) and negative/positive 12 hours conditions were maintained.

division	Total cholesterol (mg/dL)	HDL-cholesterol (mg/dL)	LDL/VLDL cholesterol (mg/dL)
Normal control	113.85±1.45	82.78±1.04	23.86±0.49
Negative control	149.08±0.69	114.35±1.46	40.39±1.49
Laboratory Example 1	129.65±1.13	88.96±1.25	29.88±0.73
Laboratory example 2	124.39±2.35	86.59±1.30	28.22±0.72
Laboratory Example 3	114.77±1.94	81.77±1.37	25.24±0.39

Referring to Table 3, when the samples of Experimental Examples 1 to 3 were applied, the concentration of blood cholesterol was found to be significantly lower than that of the negative control group, and thus, it was found to have an excellent effect on lowering the concentration of blood cholesterol.

As a result, a pharmaceutical composition using a processed fish and/or a processed soybean according to an embodiment of the present invention has the ability to improve blood circulation, improve blood triglycerides, improve blood cholesterol and/or inhibit angiotensin converting enzyme through the above-described technical configuration Is confirmed.

In addition, with respect to toxicity, the composition of the present invention can exert the above-described effects without side effects such as liver toxicity, gastrointestinal disorders and carcinogenicity by using natural fish resources used as daily foods.

As described above, the present invention has been described with reference to preferred embodiments of the present invention, but those of ordinary skill in the art of the present invention can see the present invention within the scope not departing from the spirit and scope of the invention described in the following claims. It will be appreciated that various modifications and changes can be made to the invention.

Claims (9)

1. Hyperlipidemia, dyslipidemia, hypercholesterolemia, hypertriglyceridemia, hypertension, arteriosclerosis, coronary heart disease, stroke, fatty liver, thrombosis and obesity, including at least one selected from fish processed products and soybean processed products as active ingredients Pharmaceutical composition for the prevention or treatment of one or more selected diseases.
2. The pharmaceutical composition according to claim 1, wherein the processed fish is at least one selected from dried fish, semi-dried fish, crushed raw fish, fish meal meju and fish sauce.
3. The pharmaceutical composition of claim 1, wherein the fish product is a fermented product.
4. The pharmaceutical composition according to claim 2, wherein the fish meal meju contains 20% by weight or less of fish meal based on the total weight of the meju when the meju is molded.
5. The method of claim 1, wherein the fish are anchovies, octopus, squid, sardines, cutlass, herring, trouts, mackerel, smelt, canary, yellowtail, skates, tuna, horse mackerel, saury, konja, badorachi, gulbi, pollock, yangmiri, A pharmaceutical composition, characterized in that at least one selected from mussels, clams, shrimp and blue crab.
6. The pharmaceutical composition according to claim 1, wherein the soybean processed product is at least one selected from fermented soybeans, meju, fish meal meju, miso and soy sauce.
7. The pharmaceutical composition of claim 1, wherein the soybean processed product is a fermented fermented product.
8. The pharmaceutical composition according to claim 1, which is provided in a dosage form for oral administration, transdermal administration, or injection administration.
9. The pharmaceutical composition according to any one of claims 1 to 8, wherein the pharmaceutical composition has at least one activity selected from improving blood circulation, inhibiting blood triglycerides, inhibiting blood cholesterol, and inhibiting angiotensin converting enzyme.

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