KR101732882B1 - Composition for preventing or treating lipid metabolism-related diseases containing extract of lily of the valley - Google Patents

Abstract

The present invention relates to a composition capable of preventing, ameliorating or treating diseases caused by abnormal fat metabolism, including the extract of Liliaceae.

Description

TECHNICAL FIELD The present invention relates to a composition for prevention or treatment of a lipodystrophy disorder, which comprises an extract of Liliaceae,

The present invention relates to a composition capable of preventing, ameliorating or treating diseases caused by abnormal fat metabolism, including the extract of Liliaceae.

Lipid metabolism is a generic term for the reaction of lipids in vivo. Cells of the body are controlled by energy consumption to inhibit energy metabolism, which is known to cause metabolic diseases related to fat metabolism disorders such as obesity and diabetes.

Although some substances have been developed for the treatment of abnormal lipid metabolism, these substances do not act on non-metabolized fat, which is the root cause of the disease, . In addition, since the therapeutic substances are resistant to long-term use and cause side effects, it is necessary to develop a substance capable of treating abnormal diseases without such limitations.

Korean Patent Publication No. 10-2007-0096434

It is an object of the present invention to provide a composition which is capable of preventing, ameliorating or treating diseases caused by fat metabolism.

In order to accomplish the above object, the present invention provides a pharmaceutical composition for preventing or treating fat metabolism disorder, comprising the extract of Liliaceae bark as an active ingredient.

The present invention also provides a health food composition for preventing or ameliorating a fat metabolism disorder disease, which comprises an extract of Liliaceae as an active ingredient.

The extract of Liliaceae, which is an active ingredient of the present invention, can lower blood lipid and blood cholesterol concentration and thus can be used for prevention, treatment or improvement of diseases caused by fat metabolism abnormality. In particular, the extract of Liliaceae, which is an active ingredient of the present invention, is useful because it can reduce LDL-cholesterol and triglyceride called bad cholesterol in vivo. In addition, the extract of Liliaceae, which is an active ingredient of the present invention, can reduce the arteriosclerosis index and thus can be usefully used for the treatment of arteriosclerosis and its complications. The composition according to the present invention also has an advantage that it is natural-friendly as well as easily obtainable in everyday life since it contains an extract derived from nature as an active ingredient. Therefore, it is useful in the prevention or treatment of a fat metabolism disorder which is hard to cure and needs to be managed for a lifetime, since the disease can be effectively treated without side effects.

FIG. 1 shows the result of blood sampling after administering the extract of Liliaceae to a mouse inducing hyperlipidemia.
FIG. 2 shows the result of confirming that the blood lipid concentration is lowered by administration of the extract of Liliaceae.
FIG. 3 shows the result of confirming that the arteriosclerosis index is lowered by administration of the Lily of the Valley.

In one aspect, the present invention relates to a pharmaceutical composition for preventing or treating fat metabolism disorder, which comprises an extract of Liliaceae as an active ingredient.

In another aspect, the present invention relates to a health food composition for preventing or ameliorating a fat metabolism disorder disease, which comprises an extract of Liliaceae as an active ingredient.

In the present specification, "lily of the valley" is a plant belonging to the family Liliaceae having the scientific name of Convallaria keiskei , and is distributed in Korea, Japan, China, and East Siberia. The lily of the valley is also called as the feast of Oryza sativa L., L. var.

In the present specification, the "lily of the valley extract" can be extracted using the ground or underground portion of the lily of the valley plant without restriction. For example, the ground portion may be, but is not limited to, flowers, stems, leaves or seeds, and the ground portion may also include roots and the like, but the present invention is not limited thereto. In addition, in the present specification, the lily of the valley may be used without limitation in the growing stage of the plant.

As used herein, the term " active ingredient "alone refers to an ingredient that exhibits the desired activity or that can exhibit activity with a carrier that is not itself active.

As used herein, the "Lily of the Valley " extract may be a crude extract of a solvent selected from the group consisting of water, alcohol, or a combination thereof, but includes any substances obtained by extracting Lily of the valley plants by an extraction method . The alcohol may be a C ₁ -C ₆ alcohol, specifically methanol or ethanol. The method for preparing the extract may be a conventional extraction method such as supercritical extraction, subcritical extraction, high-temperature extraction, high-pressure extraction, ultrasonic extraction, or the like using XAD and HP-20 adsorbent resins. Method can be used. Specifically, it may be warmed and refluxed or extracted at room temperature, but is not limited thereto. Further, after the extraction, a method such as concentration or lyophilization may be additionally carried out.

In the present specification, the "Lily of the valley extract" includes fractions obtained by concentrating the same, that is, the so-called lily of the valley.

As used herein, the term "fat metabolism" refers collectively to the reaction of synthesis and degradation of fats in vivo.

In the present specification, the term "abnormal lipid metabolism" refers to a disease caused by an abnormality in the synthesis and degradation of the in vivo fat, and refers to a disease caused by obesity and obesity (so-called complications) It will be apparent to those skilled in the art that it includes vascular diseases.

In a composition according to one aspect of the present invention, the lipid metabolic disorder is selected from obesity, hyperlipidemia, arteriosclerosis, hypertension, ischemic heart disease, coronary artery disease, angina pectoris, myocardial infarction, atherosclerosis (arteriosclerosis), stroke and arrhythmia May be one or more selected from the group.

The composition, which is an aspect of the present invention, can reduce the concentration of LDL-cholesterol and triglyceride, which are called bad lipids, generally bad cholesterol, and reduce the arteriosclerosis index, And can be usefully used for the treatment of abnormal diseases.

In one aspect of the present invention, the composition may comprise 0.0001 to 80% by weight of Liliaceae extract, based on the total weight of the composition. If the composition of one aspect of the present invention contains less than 0.0001% of the extract of Liliaceae, the effect on the treatment of fat metabolism disorder diseases is insignificant and the treatment speed may be slowed. If the composition contains more than 80% It is not appropriate. In view of the above, the composition is preferably used in an amount of 0.005 to 78 wt%, 0.01 to 76 wt%, 0.05 to 74 wt%, 0.1 to 72 wt%, 0.5 to 70 wt%, 1 to 68 wt% By weight or 5 to 66% by weight.

In the pharmaceutical composition according to one aspect of the present invention, the term "for the prevention or treatment " of the abnormal lipid metabolism includes both the prevention of the disease or the treatment of the disease. There is no limitation to the method of prevention or treatment, and the blood lipid content can be fundamentally reduced to prevent or treat the disease, but the present invention is not limited thereto.

When the composition according to the present invention is applied to a pharmaceutical composition, it can be formulated into an oral or parenteral dosage form in the form of solid, semi-solid or liquid by adding a commercially available inorganic or organic carrier using the above- have.

Examples of the agent for oral administration include tablets, pills, granules, capsules, powders, fine granules, powders, emulsions, syrups and pellets. Examples of the parenteral administration agent include injections, drops, ointments, lotions, sprays, suspensions, emulsions, suppositories, and the like. In order to formulate the active ingredient of the present invention, it can be easily formulated according to the conventional method. Surfactants, excipients, coloring agents, spices, preservatives, stabilizers, buffering agents, suspending agents and other adjuvants can be suitably used.

The pharmaceutical composition according to the present invention may be administered orally, parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously and the like.

The effective ingredients of the pharmaceutical composition of the present invention will vary depending on the age, sex, weight, pathological condition and severity of the subject to be treated, administration route or judgment of the prescriber. Determination of the amount of application based on these factors is within the level of ordinary skill in the art and its daily dose is, for example, from 0.1 mg / kg / day to 100 mg / kg / day, more specifically from 5 mg / kg / day to 50 mg / / Day, but is not limited thereto.

As used herein, the term "for the purpose of improving or preventing" is intended to include the use of lowering or alleviating the degree of the disease. Specifically, it may include lowering or alleviating the degree of already existing fat metabolism disorder, and considering that the effective ingredient of the composition of the present invention fundamentally reduces blood lipid, which is a causative substance of fat metabolism disorder disease, But is not limited thereto.

The composition may be processed into a drink, fermented milk, cheese, yogurt, juice, probiotic agent, and health supplement food or the like, and may be used in various other food additives.

In one embodiment, the composition may contain other ingredients or the like that can give synergistic effects to the main effect within a range that does not impair the intended main effect of the present invention. For example, additives such as perfume, coloring agent, bactericide, antioxidant, preservative, moisturizing agent, thickening agent, inorganic salt, emulsifier and synthetic polymer substance may be further added for improvement of physical properties. In addition, it may further contain auxiliary components such as water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymeric polysaccharides and seaweed extract. The above components may be mixed and selected without difficulty by those skilled in the art depending on the purpose of formulation or use, and the amount thereof may be selected within a range that does not impair the objects and effects of the present invention.

The composition according to the present invention may be in various forms such as a solution, an emulsion, a viscous mixture, a tablet, a powder, etc., and may be administered by various methods such as simple drinking, injection administration, spraying or squeezing.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for illustrating the present invention and that the scope of the present invention is not construed as being limited by these embodiments.

[ Example ] Preparation of Lily of the Valley

The lily of the valley was shredded and shredded, and 697 g of this ground product was refluxed three times and extracted with 70% ethanol. The extract was filtered, concentrated under reduced pressure, and lyophilized to obtain 205.57 g of a solid extract at a yield of 29.49%

[ Experimental Example  1] induction of lipid increase in mouse and administration of sample of Lily of the Valley

The following experiments were carried out in accordance with the method of Dominique H, Paul H. and David NB, "Effect of the lipase inhibitors, Triton WR-1339 and tetrahydrolipstation on the synthesis and secretion of lipids by rat hepatocytes", FEBS Letters, 286, 186-188, 1991 ) Were used.

An ICR-derived mouse was used in the experiment to produce an animal produced from Taconic (USA) in BioLink. ICR mice were orally administered once a day at a concentration of 10 mg / kg (Example 1) and 50 mg / kg (Example 2) for 2 weeks, respectively, for 2 weeks. Then, Triton WR-1339 (Sigma Aldrich, Korea) administered after fasted before 24 hours, by injection of Triton WR-1339 200 mg / kg in the mouse tail vein and causing hyperlipidemia, a CO ₂ gas after 18 hours, After anesthesia, the blood was collected from the mice. As a positive control group, mice of the same kind were injected with 200 mg / kg of Triton WR-1339 alone to induce hyperlipemia. The mice of the same kind, which were not treated with the negative control group, . Triton WR-1339 inhibits cell lipase activity and increases triglyceride and LDL in the blood and increases the concentration of high molecular weight Apo B, free or ester-bound cholesterol, phospholipid and fatty acid, and also inhibits intracellular lipase activity And increases the accumulation of intracellular triglycerides.

[Experimental Example 2] Determination of blood shape and measurement of triglyceride in a lipid-induced mouse

The negative control (Control), the positive control (Vehicle) obtained in the above-mentioned Experimental Example 1, and the test group of Example 1 and Example 2 were taken and pictures were taken. As can be seen from Fig. 1, in the positive control group, an opaque fat layer separated from the blood layer was observed, whereas in the test group of Example 1 and Example 2, it was confirmed that the opaque fat layer hardly existed I could. Particularly, in Example 2, clear plasma was observed to the extent similar to the negative control (Control).

The separated blood was centrifuged to separate blood cells and plasma. At this time, the turbidity of the separated plasma was observed, and the triglyceride was measured using a measurement kit (BioVision, USA) employing an enzyme method using glycerol oxidase. The measurement was performed by preparing an enzyme solution, reacting plasma with triglyceride standard, and measuring the absorbance at 540 nm with an ELISA reader to calculate plasma triglyceride concentration, and FIG. 2 was obtained. As a result, it was confirmed that the amount of triglyceride of the positive control vehicle (Vehicle) which rose steeply decreased in the experimental groups of Examples 1 and 2 in which the extract of L. bark extract was administered, and was controlled to a similar amount to the negative control (Control).

[Experimental Example 3] Measurement of total cholesterol, HDL-cholesterol and LDL-cholesterol in lipid-increasing mice

Total cholesterol, HDL-cholesterol, and LDL-cholesterol in each experimental group were measured using the plasma isolated in Experimental Example 2. The total cholesterol was determined by measuring the absorbance at 500 nm by reacting the plasma and cholesterol standards with the enzyme solution in the same manner as in the measurement of triglyceride using an enzyme assay kit (BioVision, USA) using cholesterol oxydase. HDL-cholesterol was measured using a kit (BioVision, USA) using Phosphotungstic acid-MgCl ₂ precipitation method. Specifically, plasma was reacted with HDL-cholesterol measurement solution and incubated for 5 minutes at 37 ° C. And the total cholesterol was quantitatively determined using the supernatant alone. LDL-cholesterol was calculated using the following equation (1) (Fridwald equation) after calculating the concentrations of triglyceride, total cholesterol, and HDL-cholesterol.

[Equation 1]

Fridwald formula: [LDL-cholesterol] = [total cholesterol] - {[HDL-cholesterol] + [triglyceride / 5]}

The concentrations of total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) in each experimental group are shown in Table 1 below.

As a result, it was confirmed that the total cholesterol and LDL-cholesterol amounts of the positive control vehicle (Vehicle) which rose steeply decreased rapidly in the experimental groups of Examples 1 and 2 administered with the extract of Liliaceae, and were adjusted to a similar amount to the negative control there was. In particular, according to the results of Example 1, it was confirmed that the concentration of HDL-cholesterol, which is a good cholesterol, increased rather than the positive control group by administering the extract of Liliaceae.

[Experimental Example 4] Measurement of atherosclerotic risk index in lipid-increasing mice

Using the results obtained in Experimental Example 3, the arteriosclerosis risk index was measured. A method for measuring the arteriosclerosis risk index was conducted by M. Doblasova in 2004 using the method of Clinical Chemistry, specifically using the following equation (2).

&Quot; (2) "

Atherogenic index = total cholesterol / HDL-cholesterol

As a result, as shown in FIG. 3, the arteriosclerosis index of the positive control vehicle (Vehicle) which rose steeply decreased rapidly in the experimental groups of Examples 1 and 2 administered with the Lolium berry extract, and was adjusted to an amount similar to the negative control I could confirm.

The composition according to the present invention can be applied to various formulations as described below, but is not limited thereto.

 [Formulation Example 1] Soft capsule

The soft capsules were prepared by mixing 330 mg of Liliaceae extract, 50 mg of red ginseng extract, 2 mg of palm oil, 8 mg of palm kernel oil, 4 mg of yellow pearls, and 6 mg of lecithin, and filling them with 400 mg per capsule according to a conventional method.

[Formulation Example 2] Tablets

Granules were formed by mixing 150 mg of Liliaceae extract, 100 mg of glucose, 50 mg of red ginseng, 96 mg of starch and 4 mg of magnesium stearate, and then 30 mg of ethanol was added thereto to form granules. The granules were then dried at 60 ° C., Lt; / RTI >

[Formulation Example 3] Granules

The granules were formed by mixing 150 mg of Liliaceae extract, 100 mg of glucose, 50 mg of red ginseng extract and 600 mg of starch and 100 mg of 30% ethanol, and dried at 60 to form granules. The final weight of the contents was 1 g.

[Formulation Example 4] Drinking agent

150 mg of Liliaceae extract, 10 g of glucose, 50 mg of red ginseng extract, 2 g of citric acid and 187.8 g of purified water were mixed and filled in a bottle. The final volume of the contents was adjusted to 200 ml.

[Formulation Example 5] Preparation of health food

Lily of the valley ................... 1000 mg

Vitamin mixture

Vitamin A Acetate ....................... 70 ㎍

Vitamin E ................................ 1.0 mg

Vitamin B1 ................................ 0.13 mg

Vitamin B2 ............................... 0.15 mg

Vitamin B6 .................................. 0.5 mg

Vitamin B12 ........................ 0.2 ㎍

Vitamin C .................................. 10 mg

Biotin ..................................... 10 μg

Nicotinic acid amide ............................ 1.7 mg

Folic acid ....................................... 50 ㎍

Calcium pantothenate .............................. 0.5 mg

Mineral mixture

Ferrous sulfate ................................ 1.75 mg

Zinc oxide .................................. 0.82 mg

Magnesium carbonate .............................. 25.3 mg

Potassium Phosphate ............................... 15 mg

Secondary calcium phosphate ............................... 55 mg

Potassium citrate ................................. 90 mg

Calcium carbonate ................................. 100 mg

Magnesium chloride .............................. 24.8 mg

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

[Formulation Example 6] Preparation of health drink

Lily of the valley ... 1000 mg

Citric acid ........................., .. 1000 mg

Oligosaccharides ........................... 100 g

Plum concentrate .......................... 2 g

Taurine .............................. 1 g

Purified water was added to the mixture to complete 900 ml

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, ≪ / RTI >

Although the composition ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the blending ratio according to the regional or national preference such as the demand level, demand country, use purpose, and the like. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. something to do. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (6)

A pharmaceutical composition for lowering blood cholesterol comprising an ethanol extract of a root of Liliaceae as an active ingredient. A health food composition for lowering blood cholesterol comprising an ethanol extract of a root of Liliaceae as an active ingredient. The method according to claim 1,
The composition may lower blood cholesterol and prevent or treat at least one selected from the group consisting of hyperlipidemia, arteriosclerosis, hypertension, ischemic heart disease, coronary artery disease, angina pectoris, myocardial infarction, atherosclerosis (arteriosclerosis), stroke and arrhythmia ≪ / RTI > or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for lowering blood cholesterol. 3. The method of claim 2,
The composition may lower cholesterol in the blood and improve one or more selected from the group consisting of hyperlipidemia, atherosclerosis, hypertension, ischemic heart disease, coronary artery disease, angina pectoris, myocardial infarction, atherosclerosis (arteriosclerosis), stroke and arrhythmia Phosphorus, and cholesterol in blood. The method according to claim 1,
Wherein the composition comprises 0.1 to 20% by weight of an ethanol extract of Liliaceae root from the total weight of the composition. 3. The method of claim 2,
Wherein the composition comprises 0.1 to 20% by weight of an ethanol extract of Liliaceae root from the total weight of the composition.

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