KR20180132571A - A composition comprising extract of ligularia fischeri and momordica charantia for preventing and treating and manufacturing method thereof - Google Patents

Abstract

The present invention discloses a composition containing a Ligularia fischeri extract and a Momordica charantia extract, and a production method thereof. According to an embodiment of the present invention, a pharmaceutical composition containing the Ligularia fischeri extract and the Momordica charantia extract in a weight ratio of 9 : 1-1 : 9, so as to prevent and treat diseases selected from the group consisting of diabetes, non-alcoholic fatty liver disease, renal failure, and hyperlipemia.

Description

FIELD OF THE INVENTION [0001] The present invention relates to a composition for preventive and therapeutic treatment,

The present invention relates to a composition for preventive and therapeutic treatment, which comprises an extract of Ganoderma Lucidum and an extract of Ganoderma lucidum, and a method for preparing the same, and more particularly, to a method for the preparation of a composition for preventing and treating Ganoderma lucidum extract and Ganoderma lucidum extract from the group consisting of diabetic, non- To a composition for the prevention and treatment of selected diseases and a method for producing the same.

Due to recent rapid improvement in living standards, adult diseases such as hypertension, diabetes, obesity, and hyperlipemia are increasing due to excessive intake of high-calorie foods, lack of exercise, and stress due to the advancement of the industrial society. It is becoming a cause.

Diabetes mellitus is the most common non-communicable disease among modern people. It is a disease caused by insufficient secretion of insulin secreted from the pancreas, or insulin receptor abnormality and cells can not use insulin. This type of diabetes is known to be associated with genetic factors, such as obesity, dietary habits, lack of exercise, and stress. It is known that diabetes itself is not a major disease but rather a complication that occurs due to long- For example, diabetic neuropathy, dyslipidemia and resulting non-alcoholic fatty liver disease, retinopathy, cataract, nephropathy, and the like. It is a societal problem because patients can not only lead normal life, but they can also lead to fatal consequences to death. In particular, dyslipidemia, including hyperlipidemia in diabetic patients, is one of the most common diabetic complications and may be accompanied by symptoms of vascular disorders such as cerebral infarction and myocardial infarction. In addition, 50 to 75% of type 2 diabetic patients have hyperlipidemia (Akbar et al., 2003), which is associated with non-alcoholic fatty liver accumulation in the liver. In addition, end stage renal disease (ESRD) is the most important complication that leads to death among diabetic microvascular complications. Recently, diabetes is the most important and common cause in the world. 20% of diabetic patients in Korea have microalbuminuria And 14.0% were reported to present with proteinuria (Lee et al., 1995).

People with diabetes and diabetic complications should be able to slowly absorb the carbohydrates of the food they eat so as to prevent the rapid increase in blood sugar, or to improve the function of the insulin secretion and promote the glucose utilization of the cells.

Meanwhile, diabetes causes various causes, but any type of diabetes, the basic principles for the improvement of symptoms or healing is to increase the rate at which cells in each tissue are absorbed into the body after a meal, , Which is commonly applied to drugs or natural materials. For this purpose, glucagon-like peptide-1, a hormone that inhibits α-glucosidase that regulates the uptake of glucose in the small intestine or increases insulin secretion, 1, GLP-1) secreted by the mouse. In particular, the activation of glucagon-like peptide-1 has an effect of increasing insulin secretion in the body, as well as proliferation of beta cells of the pancreas, suppression of secretion of glucagon, inhibition of appetite, excellent blood pressure and lipid- For example, it is attracting attention as a next-generation diabetic therapeutic agent capable of improving hyperlipemia and non-alcoholic fatty liver disease caused thereby, and renal failure due to microvascular complications.

Meanwhile, up to now, the medical goal of medical treatment is to maintain normal blood glucose level, but various therapies have been tried in addition to diet therapy and exercise therapy, which are supplementary therapies. However, patients are increasing rapidly and their prevalence is also prolonged. As a result, the national and individual economic losses are so great that there is no scientific cure for diabetes.

Korean Patent Registration No. 10-1118451 entitled " Composition for reducing blood glucose level, which contains the extract of Tohoku Bokryei, Yeoju and Cordyceps sinensis as an active ingredient " Korean Patent Publication No. 10-1536974, "Food Composition for Preventing and Improving Diabetes Containing Mixed Extract of Yeast, Cornus oil, Omiza and Jujube," Korean Patent Registration No. 10-1686898, "Food Composition for Prevention and Improvement of Diabetes Mellitus using Yeoju, Korean Patent Publication No. 10-1688090, "antidiabetic composition containing porcine potato, rice bran, omija, Korean Patent Publication No. 10-0862096, "An antidiabetic composition comprising beta-glucan and Yejoo extract as an active ingredient"

The present invention provides a pharmaceutical composition for preventing and treating diseases selected from the group consisting of diabetic, non-alcoholic fatty liver, renal failure, and hyperlipidemia, which comprises a ginger extract and a mallow extract.

The present invention is to provide a health functional food composition for preventing and treating diseases selected from the group consisting of diabetic, non-alcoholic fatty liver, renal failure and hyperlipemia, which comprises an extract of Ganoderma lucidum and an extract of Lilac.

The present invention provides a method for preparing a pharmaceutical composition for preventing and treating diseases selected from the group consisting of diabetes mellitus, nonalcoholic fatty liver disease, renal failure and hyperlipidemia, as an active ingredient,

The present invention provides a method for preparing a health functional food composition for preventing and treating diseases selected from the group consisting of diabetes mellitus, nonalcoholic fatty liver disease, renal failure and hyperlipidemia, as an active ingredient.

The pharmaceutical composition for prevention and treatment of diseases selected from the group consisting of diabetic, non-alcoholic fatty liver, renal failure, and hyperlipidemia, which comprises an extract of Ganoderma lucidum and an extract of Ganoderma lucidum according to an embodiment of the present invention is selected from the group consisting of Ligularia fischeri extract, Momordica charantia) extract in a weight ratio of 9: 1 to 1: 9.

The pharmaceutical composition may contain the scaly extract and the rumen extract in a weight ratio of 3: 7.

The above extract and the extract of Ganoderma lucidum may increase the expression of GLP-1 (Glucagon-like peptide 1).

The ginger extract may be in the form of a liquid extract or a powder in which the liquid extract is lyophilized.

The yeast extract may be in the form of a liquid extract or a powder in which the liquid extract is lyophilized.

The pharmaceutical composition may further comprise an Olea europaea leaf extract or Rosemarinus officinalis leaf extract.

The composition may be formulated into any one of a tablet, a capsule, a powder, a granule, a pill, a liquid agent and a suspension.

The health functional food composition for prevention and treatment of diseases selected from the group consisting of diabetic, non-alcoholic fatty liver, renal failure and hyperlipidemia, which comprises the extract of Ganoderma lucidum and Lycoris chejuensis according to the embodiment of the present invention, (Momordica charantia) extract in a weight ratio of 9: 1 to 1: 9.

The method for preparing a pharmaceutical composition for prevention and treatment of diseases selected from the group consisting of diabetes mellitus, nonalcoholic fatty liver disease, renal failure and hyperlipidemia, which comprises extracts of Mugwort extract and mugwort extract according to an embodiment of the present invention, Extracting with an aqueous solution of water, an alcohol having 1 to 5 carbon atoms, or a mixed solvent thereof; Extracting the yeast with water, an alcohol having 1 to 5 carbon atoms, a alcohol or a mixed solvent thereof at 0 캜 to 90 캜 to prepare a yeast extract; And a step of preparing a mixture comprising the gherkass extract and the ganoderma extract at a weight ratio of 9: 1 to 1: 9.

The pharmaceutical composition may further comprise an olive leaf extract or a rosemary leaf extract.

The olive leaf extract or the rosemary leaf extract may be extracted at 0 캜 to 90 캜 with water, an alcohol having 1 to 5 carbon atoms, or a mixed solvent thereof.

The composition according to embodiments of the present invention may be used in combination with an extract of Ganoderma lucidum var. Sp. Having an alpha-glucosidase inhibition, a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist activity or GLP-1 (Glucagon-like peptide- It is possible to prevent and treat diseases selected from the group consisting of diabetes mellitus, non-alcoholic fatty liver disease, renal failure and hyperlipemia using natural materials.

Compositions in accordance with embodiments of the present invention can simultaneously prevent and treat type 2 diabetes by having both alpha-glucosides inhibition, PPAR gamma agonist efficacy and GLP-1 receptor agonist efficacy.

The composition according to the embodiments of the present invention can increase the expression of GLP-1 by including a ginger extract and a ganoderma extract.

The composition according to the embodiments of the present invention can reduce the blood glucose elevation, decrease the blood glycosylated hemoglobin, and reduce the triglyceride and cholesterol in the blood by including the ginger extract and Yeast extract.

The composition according to the embodiments of the present invention increases the expression of GLP-1, thereby promoting insulin secretion, thereby consuming sugars and fat accumulated in the liver, thereby suppressing non-alcoholic fatty liver.

The composition according to embodiments of the present invention can increase the expression of GLP-1, increase the excretion of sodium in the kidney, and reduce the rate of nephropathy filtration, thereby preventing and treating renal failure.

Figure 1 shows changes in GLP-1 receptor content in each group.
Figure 2 shows the amount of fat accumulation in liver cells in each group.
FIG. 3A is a graph showing a change amount of blood urea nitrogen (BUN) in each group, FIG. 3B is a graph showing a change amount of serum creatine according to an extract, FIG. And the amount of uric acid in the urine.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings and accompanying drawings, but the present invention is not limited to or limited by the embodiments.

The terminology used herein is for the purpose of illustrating embodiments and is not intended to be limiting of the present invention. In the present specification, the singular form includes plural forms unless otherwise specified in the specification. &Quot; comprises "and / or" comprising ", as used herein, does not exclude one or more other elements.

As used herein, the terms "embodiment," "example," "side," "example," and the like should be construed as advantageous or advantageous over any other aspect or design It does not.

Also, the term 'or' implies an inclusive or 'inclusive' rather than an exclusive or 'exclusive'. That is, unless expressly stated otherwise or clear from the context, the expression 'x uses a or b' means any of the natural inclusive permutations.

Also, the phrase "a" or "an ", as used in the specification and claims, unless the context clearly dictates otherwise, or to the singular form, .

It will also be understood that when an element such as a film, layer, region, configuration request, etc. is referred to as being "on" or "on" another element, And the like are included.

The pharmaceutical composition for prevention and treatment of diseases selected from the group consisting of diabetic, non-alcoholic fatty liver, renal failure, and hyperlipidemia, which comprises an extract of Ganoderma lucidum and an extract of Ganoderma lucidum according to an embodiment of the present invention is selected from the group consisting of Ligularia fischeri extract, Momordica charantia) extract.

It is a perennial plant of chrysanthemum as a perennial plant. Goryeo is a kind of bract which is characterized by broad leaves. It is mainly taken in the form of herbs, raw vegetables, and wrapped in Korea.

Vitamin A (780 RE / 100 g), β-carotene (4681), and β-carotene are the most commonly found in the nutrients, especially vitamin A, B1, B2, B3 and C and β-carotene. It is known that the contents of calcium (241 mg / 100 g), fibrin (1.7 g / 100 g) and iron (5.7 mg / 100 g) are relatively higher than those of other vegetables It is evaluated as high value.

In addition, it has been reported that the ginseng has various nutritional components, especially vitamin A, B1, B2, C, E, beta carotene and niacin, which are relatively higher than other hay and are highly effective in inhibiting carcinogenic substances.

It can be used without restriction, such as cultivated or marketed.

The extract can be extracted by adding an extracting solvent, and the extracting solvent used for the production of the extract is not limited thereto, but may be selected from water, an organic solvent or a mixture thereof.

The organic solvent may be a polar solvent such as an alcohol having 1 to 5 carbon atoms, ethyl acetate or acetone, a nonpolar solvent such as ether, chloroform, benzene, hexane or dichloromethane, or a mixture thereof. For example, the alcohol having 1 to 5 carbon atoms may be selected from methanol, ethanol, propanol, butanol, isopropanol, and the like.

Preferably, water, an alcohol having 1 to 5 carbon atoms, or a mixed solvent thereof may be used as the extraction solvent used for the preparation of the ginger extract.

The method of extracting a ginger extract can be carried out by a method using an extraction device such as hot water extraction, immersion extraction, reflux cooling extraction, supercritical extraction, subcritical extraction, high temperature extraction, high pressure extraction, ultrasonic extraction, or adsorption resin containing XAD and HP- Or the like may be used. Preferably, the method for extracting a ginger extract may be obtained by treating the extract solvent with hot water and concentrating it under reduced pressure.

In addition, the ginger extract may be in the form of a powder in which the liquid extract or the liquid extract is lyophilized.

A pharmaceutical composition containing an extract of Ganoderma lucidum according to the present invention can be used for the treatment of angioma, angiofibroma, arthritis, diabetic retinopathy, retinopathy of prematurity, neovascular glaucoma, corneal disease caused by neovascularization, degeneration reaction, degeneration of spot, pterygium, The present invention can be used as an agent for preventing or treating diseases caused by angiogenesis including cancer, hyperplasia, granulomatous conjunctivitis, psoriasis, capillary dilatation, pyogenic granuloma, seborrheic dermatitis, acne and the like, or cancer metastasis inhibitor.

In addition, in the present invention, the ginger extract provides the therapeutic effect of diabetic complications. Diabetic complications are diabetic complications that lead to hyperglycemia and protein reactions that irreversibly progress to produce advanced glycation endproducts (AGEs) that cross-link with other proteins in the blood or tissue.

Specifically, in the present invention, the diabetic complication having the therapeutic effect of the extract of Gramineae extract may be diabetic vascular disorder, diabetic neuropathy or diabetic infection, and preferably diabetic retinopathy, diabetic cataract, diabetic retinopathy, cataract, diabetic nephropathy, diabetic neuropathy, diabetic vascular complications, and the like, more preferably diabetic retinopathy, diabetic cataract or diabetic nephropathy.

The diabetic complication therapeutic activity of the present invention was tested by inhibiting the formation of Advanced Glycation Endproducts (AGEs) and inhibiting Aldose reductase.

Momordicacharantia is a fruit of the vine plant of cucurbitaceae, also called bitter melon in English name. In addition, Yeoju contains 120 mg of 100 g of vitamin C, which is significantly higher than 80 mg of strawberry, 40 mg of cabbage, and 90 mg of lemon, and Vitamin C in Yeoju is contained in juicy pulp Even if heated, it is hardly destroyed.

As described above, since the yeast used in the present invention is a food material used for edible purposes, it has no adverse effect on long-term ingestion and is a natural material which does not cause tolerance of the patient.

The part of the yeast extract which can be separated is not particularly limited, but may be at least one selected from the group consisting of leaves, stems, fruits and seeds of Yeoju. Preferably, berries are selected. More preferably, it is preferable that the fruity portion of the fruity green with the green skin is selected.

Yeoju can be extracted by adding an extraction solvent. The extraction solvent used for the preparation of the yeast extract may be any solvent selected from water, organic solvents, spirits, or mixtures thereof, although not limited thereto.

The organic solvent may be a polar solvent such as an alcohol having 1 to 5 carbon atoms, ethyl acetate or acetone, a nonpolar solvent such as ether, chloroform, benzene, hexane or dichloromethane, or a mixture thereof. For example, the alcohol having 1 to 5 carbon atoms may be selected from methanol, ethanol, propanol, butanol, isopropanol, and the like.

Preferably, water, an alcohol having 1 to 5 carbon atoms, alcohol, or a mixed solvent thereof may be used as an extraction solvent used for the production of a ginger extract.

The method of extracting Yuzu extract can be carried out by a method using an extraction device such as hot water extraction, immersion extraction, reflux cooling extraction, supercritical extraction, subcritical extraction, high temperature extraction, high pressure extraction and ultrasonic extraction, or a method using XAD and HP- Or the like may be used. Preferably, the method for extracting Y. japonica extract can be obtained by treating with an extraction solvent, extracting it by hot water, and concentrating it under reduced pressure.

In addition, the Yeast extract may be in the form of a powder in which the liquid extract or the liquid extract is lyophilized.

In the pharmaceutical composition according to the embodiment of the present invention, the Ganoderma lucidum extract and the Lilac extract are contained in a weight ratio of 9: 1 to 1: 9.

The extract of Ganoderma lucidum and Lycium chinense is contained in a weight ratio of 9: 1 to 1: 9, thereby having an effect of inhibiting blood glucose.

Table 1 is a table showing the inhibition rate of blood glucose increase according to the mixing ratio of Ganoderma lucidum extract and Yeast extract.

Gijux: Yeoju 0 weeks 4 weeks Inhibition rate Control group 370 ± 31.2 504 ± 43.9 - 10: 0 (stand alone) 376 ± 100.5 473 ± 78.3 6.1 9: 1 357 ± 48.1 465 ± 71.7 7.7 7: 3 352 ± 62.2 421 ± 70.5 16.4 5: 5 369 ± 61.5 433 ± 83.6 14.0 3: 7 341 ± 51.6 393 + - 71.0 22.1 1: 9 367 ± 40.2 435 ± 28.5 13.6 0:10 (Yeoju only) 363 ± 47.5 444 ± 53.5 12.0

In Table 1, the composition containing only the ginger extract alone (10: 0) was prepared in the same manner as in Comparative Example 6, and the composition containing only the extract of Yejoo extract (0:10) was the same as that of Comparative Example 7 , And the extract of Ganoderma lucidum / L. ganoderma containing Ganoderma lucidum L. at a weight ratio of 3: 7 was prepared in the same manner as in Preparation Example 1 below.

In addition, except for changing the weight ratio of ganoderma lucidum: luteum in Preparation Example 1 below, the weight ratio of Ganoderma lucidum to Ganoderma lucidum containing 9: 1, 7: 3, 5: 5 and 1: Was prepared in the same manner.

Table 1 shows the blood glucose lowering efficacy in diabetic mice induced by high fat diet and streptozotocin to determine the mixing ratio of ginger extract and goat juice extract. The extracts of Ganoderma lucidum and Lycium chinense were mixed at a weight ratio of 0:10 ~ 10: 0, and the final concentration was 100 mg / kg. After oral administration for 4 weeks, the blood glucose lowering effect was measured.

As shown in Table 1, the inhibition rate of glucose uptake was increased in the mice administered with the extract of Ganoderma lucidum extract and L. rhamnosus extract, compared with the mice administered alone with the Ganoderma lucidum extract or L. japonica extract. The highest inhibition rate of glucose uptake was 22.1% in mice administered with extracts.

On the other hand, the mixed extract of Ganoderma lucidum / L. ganoderma L. containing L. japonica at a weight ratio of 9: 1 showed lower inhibition rate of blood glucose increase than a composition containing L. japonicus extract alone, The extract of Ganoderma lucidum / L. ganoderma has an inhibitory effect on alpha-glucosidase which is not exhibited in the composition containing L. japonica extract alone. Therefore, it can have an effect of controlling blood glucose control better than a composition containing L. japonica extract alone.

Therefore, preferably, the pharmaceutical composition according to the embodiment of the present invention may contain the ginger extract and the ganoderma extract at a weight ratio of 3: 7.

A composition comprising a ginger extract and a ganoderma lucidum extract comprises a ginger extract and a ganoderma extract having an alpha-glucosides inhibitory effect, a PPAR gamma agonist activity effect or a GLP-1 receptor agonist agonist effect, Renal failure and hyperlipemia can be prevented and treated.

The ginger extract contained in the pharmaceutical composition according to the embodiment of the present invention has an excellent alpha-glucosidase inhibitory effect.

Alpha-Glucosidase enzyme is an enzyme that hydrolyzes oligosaccharide, which is digested by meals into small intestine, into monosaccharide. This enzyme inhibitor slows the postprandial increase of blood sugar by delaying the absorption of carbohydrates. Examples of such alpha-glucosidase inhibitors include acarbos and miglitol, which were developed by Bayer, Germany in 1977. They were developed as diabetic and obesity treatment agents, .

In addition, the extract of Yeast extract contained in the pharmaceutical composition according to the embodiment of the present invention has a superior peroxisome proliferator activated receptor-gamma (PPARγ) agonist effect.

PPARγ, a member of the nuclear hormone receptor family, is known to be a receptor for the Thiazolidinedione (TZD) family, which increases insulin sensitivity in energy metabolism. PPARγ plays an important role in the lipid metabolism of adipose tissue depending on the nutritional status. In particular, the expression of PPARγ is increased in the postprandial state, thereby increasing the activity of the gene that carries the absorption and capture of the fatty acid. Insulin resistance patients are difficult to use glucose. In order to increase the energy efficiency in the body, free fatty acids are released from adipocytes. Thiazolidinediones absorb and capture these free fatty acids to lower the free fatty acid concentration in the body , And increases insulin sensitivity.

In addition, the pharmaceutical composition according to the embodiment of the present invention can increase the expression of GLP-1 (Glucagon-like peptide 1) by including both the extract of Ganoderma lucidum and the extract of Lilac.

GLP-1 is an inhibitor of insulin secretion stimulated by intestinal nutrients or blood sugar concentrations. It stimulates insulin secretion and stimulates insulin secretion. It promotes insulin secretion, not inhibiting glucose uptake And thus it is in the spotlight as a next-generation therapeutic agent for the treatment of type 2 diabetes. The activation of GLP-1 not only has an effect of increasing insulin secretion in the body but also has effects such as proliferation of beta cells of pancreas, suppression of secretion of glucagon, inhibition of appetite, and other effects of improving blood pressure and lipid.

Accordingly, the pharmaceutical composition according to the present invention increases the expression of GLP-1 (Glucagon-like peptide 1), thereby strongly promoting insulin secretion stimulation in the pancreas, thereby enhancing insulin secretion, Can be prevented and treated.

Type 2 diabetes mellitus is favored by a combination of diabetes treatment with other mechanisms rather than monotherapy, which is clinically treated with one drug, due to the specificity of the disease. In particular, glucagon-like peptide-1 receptor agonists can reduce the dosage when administered with a combination of a glycoprotein inhibitor (metformin family), a digestive enzyme inhibitor (acarbos family), and an insulin resistance improving (thiazolidinedione family) Can be further strengthened.

Accordingly, the pharmaceutical composition according to the embodiments of the present invention can simultaneously prevent and treat type 2 diabetes by having alpha-glucosides inhibition, PPAR gamma agonist efficacy and GLP-1 receptor agonist efficacy.

The pharmaceutical composition according to the embodiments of the present invention can reduce the increase of blood glucose, reduce the triglyceride in blood, and reduce the cholesterol and the glycated hemoglobin.

That is, the pharmaceutical composition according to the embodiments of the present invention, which includes both the extract of Ganoderma Lucidum and the extract of Ganoderma lucidum, can treat, prevent or ameliorate diseases in which blood glucose lowering is required.

More specifically, GLP-1 is secreted from the small intestine by the ingestion of food to promote postprandial insulin secretion and inhibit appetite. GLP-1 is secreted by the sugar in patients with fatty liver disease, and GLP-1 analogue promotes insulin secretion and slows gastric emptying time, thereby improving ALT improvement and liver tissue abnormalities.

Accordingly, the pharmaceutical composition according to the present invention increases the expression of GLP-1 (Glucagon-like peptide 1), thereby promoting insulin secretion, thereby consuming glucose and fat accumulated in the liver, Can be suppressed.

In addition, GLP-1 can reduce the renal sphericity filtration rate by stimulating sodium excretion in the kidneys. In other words, GLP-1 agonists can reduce proteinuria and albuminuria.

Accordingly, the pharmaceutical composition according to the present invention increases the expression of GLP-1 (Glucagon-like peptide 1), thereby increasing the excretion of sodium in the kidney and decreasing the gonadal sperm filtration rate, Can be treated.

In addition, GLP-1 receptor agonists have been shown to improve blood vessels in many clinical trials and can improve blood lipid levels by increasing energy metabolism.

Accordingly, the pharmaceutical composition according to the present invention increases the expression of GLP-1 (Glucagon-like peptide 1), thereby improving lipid in blood, thereby preventing and treating hyperlipemia.

In addition, the pharmaceutical composition according to an embodiment of the present invention may further include an Olea europaea leaf extract or Rosemarinus officinalis leaf extract.

Olive leaves are obtained from olive trees. Oleuropein, the main detectable material in olive leaves, can improve hypotension, coronary dilating and arrhythmia.

It can also improve the antihypertensive, diuretic, anti-atherosclerotic, antioxidant and hypoglycemic effects of triterpenoids extracted from olive (Olea europea) leaves. The olive leaf extract also contains other ascending phytochemicals, including rutin and hesperidin. This is essential for the ability to increase the strength of the capillary (blood vessel) and to control its permeability.

In the pharmaceutical composition according to the embodiment of the present invention, olive leaves may contain 10 parts by weight of the total composition, thereby enhancing the expression of GLP-1.

The effect of mixing less than 10 parts by weight of the olive leaf in the pharmaceutical composition of the present invention is insufficient, and when the mixture is mixed with 10 parts by weight or more, the relative ratio of the ginger extract and the yeast extract is lowered, and the effect of GLP- .

In the pharmaceutical composition according to the embodiment of the present invention, rosemary leaves may contain 10 parts by weight of the total composition, thereby enhancing the expression of GLP-1.

In the pharmaceutical composition according to the embodiment of the present invention, when the rosemary leaves are mixed in an amount of 10 parts by weight or less, the effect is not enhanced. When the mixture is mixed with 10 parts by weight or more of rosemary leaves, Is low.

The pharmaceutical composition according to an embodiment of the present invention may be prepared in any one of formulations selected from tablets, capsules, powders, granules, pills, liquid agents and suspensions.

In addition, the health functional food composition for prevention and treatment of diseases selected from the group consisting of diabetic, non-alcoholic fatty liver, renal failure and hyperlipidemia, which comprises the extract of Ganoderma lucidum and Lycium chinense according to the embodiment of the present invention, And Momordica charantia extract in a weight ratio of 9: 1 to 1: 9.

The health functional food composition according to an embodiment of the present invention may have the same substance, method, content and effect as the pharmaceutical composition according to the embodiment of the present invention.

The term "health functional food" in the present invention refers to a food prepared and processed in the form of tablets, capsules, powders, granules, liquids and circles by using raw materials and components having useful functions in the human body. Here, the term "functionality" means that the structure and function of the human body are controlled to obtain nutritional effects or effects useful for health use such as physiological actions.

The health functional food of the present invention can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and ingredients that are conventionally added in the art. In addition, unlike general medicines, there is an advantage that there is no side effect that may occur when a medicine is taken for a long time by using a food as a raw material, and it is excellent in portability and the health functional food of the present invention is improved in diabetes, non- It can be ingested as an adjuvant to enhance the effect.

The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). The health food of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary foods. The above-mentioned natural carbohydrates are sugar saccharides such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and xylitol, sorbitol and erythritol. As the sweetening agent, natural sweetening agents such as tau Martin and stevia extract, synthetic sweetening agents such as saccharine and aspartame, and the like can be used.

In addition, the health functional food according to the present invention may include a proper food auxiliary additive. The term "food supplementary additive " in the present invention means a component which can be added to foods in a supplementary manner, and it can be appropriately selected and used by those skilled in the art as added to produce health functional foods of each formulation. Examples of food-aid additives include flavors such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, , a pH adjusting agent, a stabilizer, a preservative, a glycerin, an alcohol, and a carbonating agent used in a carbonated drink. However, the types of the food auxiliary additives of the present invention are not limited by these examples.

The method for preparing a pharmaceutical composition according to an embodiment of the present invention comprises the steps of: (a) preparing an extract of Ajiuchi sativa, by extracting the sea tangle with water, a C1-5 alcohol or a mixed solvent thereof at 0 ° C to 90 ° C; ) Extracting the yeast extract with water, an alcohol having 1 to 5 carbon atoms, a alcohol or a mixed solvent thereof at 0 캜 to 90 캜, and (c) By weight of the mixture.

In one embodiment of the present invention, step (a) can be conducted by extracting the sea tangle with water, an alcohol having 1 to 5 carbon atoms, or a mixed solvent thereof at 0 캜 to 90 캜.

There is a problem that the efficacy component can not be extracted when the temperature for producing an extract of Ganoderma lucidum is 0 ° C or less, and the efficacy component is destroyed when the temperature exceeds 90 ° C.

In addition, the ginger extract may be in the form of a powder in which the liquid extract or the liquid extract is lyophilized.

In one embodiment of the present invention, step (b) can be carried out by extracting the yeast extract with water, an alcohol having 1 to 5 carbon atoms, a alcohol or a mixed solvent thereof at 0 ° C to 90 ° C.

There is a problem that the efficacious ingredient can not be extracted when the temperature for preparing the extract is less than 0 ° C, and when the temperature exceeds 90 ° C, the efficacious ingredient is destroyed and the efficacy is deteriorated.

In addition, the Yeast extract may be in the form of a powder in which the liquid extract or the liquid extract is lyophilized.

In one embodiment of the present invention, the step (c) can produce a mixture comprising a scaly extract and a raspberry extract at a weight ratio of 9: 1 to 1: 9.

Preferably, a mixture comprising a ginger extract and a ganoderma extract at a weight ratio of 3: 7 can be prepared.

Also, in the method for preparing a pharmaceutical composition according to an embodiment of the present invention, a mixture including olive leaf extract and rosemary leaf extract may be prepared in step (c).

The olive leaf extract or the rosemary leaf extract can be extracted at 0 캜 to 90 캜 with water, an alcohol having 1 to 5 carbon atoms, or a mixed solvent thereof.

Preferably, the alcohol having 1 to 5 carbon atoms may include at least one selected from methanol, ethanol, isopropanol, propanol and butanol.

When the temperature for producing olive leaf extract or rosemary leaf extract is below 0 ° C, there is a problem in that the efficacious ingredient can not be extracted. When the temperature exceeds 90 ° C, the efficacious ingredient is destroyed and the efficacy is deteriorated.

In addition, the olive leaf extract or the rosemary leaf extract may be in the form of a powder in which the liquid extract or the liquid extract is lyophilized.

A method for preparing a health functional food composition according to an embodiment of the present invention comprises the steps of: (a) preparing an anthocyanin extract by extracting a green tea with water, an alcohol having 1 to 5 carbon atoms, or a mixed solvent thereof at 0 to 90 ° C (b) extracting the yeast extract with water, an alcohol having 1 to 5 carbon atoms, a alcohol or a mixed solvent thereof at 0 to 90 ° C, and (c) Lt; RTI ID = 0.0 > weight / 9. ≪ / RTI >

The method for preparing a health functional food composition according to an embodiment of the present invention may have the same materials, methods, contents, and effects as those of the pharmaceutical composition according to the embodiments of the present invention.

Production Example 1

10 kg of leaves were extracted 2 ~ 5 times at 80 ℃ for 5 hours using 30% alcohol, concentrated, and lyophilized to produce a ginger extract. Ten kilograms of lily of the valley was repeatedly extracted 2 ~ 5 times at 80 ℃ for 5 hours using a 30% alcohol, concentrated and lyophilized to prepare a lute juice extract. The mixture of 300 g of the ginger extract thus obtained and 700 g of the Yeoju extract was mixed to prepare a 3: 7 weight ratio mixture.

Production Example 2

10 kg of olive leaf was extracted repeatedly 2 to 5 times at 80 ° C for 5 hours using a 30% alcohol, and 110 g of concentrated and lyophilized olive leaf extract was added to the mixture prepared in [Preparation Example 1].

Production Example 3

10 kg of rosemary leaves were repeatedly extracted 2 to 5 times at 80 ° C for 5 hours using a 30% alcohol, and 110 g of concentrated and lyophilized rosemary leaf extract was added to the mixture prepared in [Preparation Example 1].

Experimental group and ingestion method

For this experiment, six C57BL / 6J male mice were prepared for 7 weeks of age. After the adaptation period of 1 week, the mice were separated from each other and cultivated at 12 hours intervals (7 ~ 17 hours) . 3) "Streptozotocin-treated group," 4) "Control group," 5) "Banaba leaf extract-treated group," and 6) 9) "Ganoderma lucidum extract / mixture mixture group + olive leaf extract group", 10) "Ganoderma lucidum / Luteolus extract mixture group + Rosemary extract / Lantus extract extract group" Leaf extract administration group ", which was divided into 10 groups, and was orally administered once a day for 10 weeks at a fixed time (10:00 am).

1) Dietary intake group (Comparative Example 1)

0.5 mL of saline was administered.

2) High-fat diet group (Comparative Example 2)

0.5 mL of saline was administered.

3) Streptozotocin-treated group (Comparative Example 3)

0.5 mL of saline was administered.

4) Control (Comparative Example 4)

0.5 mL of saline was administered.

5) Group treated with extract of banaba leaf (Comparative Example 5)

The leaf extract of Barnabas was dissolved in 0.5 ml of saline at a concentration of 100 mg / kg.

6) The group of the extracts of the ginger extract (Comparative Example 6)

The extracts were dissolved in 0.5 ml of saline at a concentration of 100 mg / kg.

7) Administration group of Yejoo extract (Comparative Example 7)

Yeoju extract was dissolved in 0.5 ml of saline at a concentration of 100 mg / kg.

8) Administration group of Ganoderma lucidum / Luteolus extract (Example 1)

The mixture prepared in [Preparation Example 1] was dissolved in 0.5 ml of saline at a concentration of 100 mg / kg.

9) a mixture of ginger extract / lucerne extract + olive leaf extract (Example 2)

The mixture prepared in [Preparation Example 2] was dissolved in 0.5 ml of saline at a concentration of 100 mg / kg.

10) Mixture of ginger and leek extract + rosemary leaf extract administration group (Example 3)

The mixture prepared in [Preparation Example 3] was dissolved in 0.5 ml of saline at a concentration of 100 mg / kg.

Effect of GLP-1 (Glucagon-like peptide 1) receptor on extract

Figure 1 shows changes in GLP-1 receptor content in each group.

Referring to FIG. 1, Examples 1 to 3 exhibited higher expression levels than Comparative Examples 1 to 7. In addition, the highest expression level of GLP-1 receptor was shown in Example 2, which further included olive leaf extracts of Examples 1 to 3, and Example 3, which further included rosemary leaf extract.

The alpha - Glucosides  Inhibitory effect

Table 2 is a table showing the inhibition rate of alpha-glucosidate according to the mixed extract of Ganoderma sp.

Concentration of extract (/ / mL) Alpha- Glucosides  Inhibition rate % ) Comparative Example  6 Comparative Example  7 Example  One Acabos 100 44.40 ± 1.51 no effect 44.24 + - 1.01 48.87 ± 1.05 50 41.77 ± 1.80 no effect 39.02 + - 0.61 38.20 ± 1.41 25 23.98 ± 0.89 no effect 27.91 + - 0.98 32.70 +/- 1.65 12.5 6.84 ± 2.43 no effect 23.84 ± 0.79 23.66 ± 0.92 6.25 1.99 ± 1.53 no effect 24.97 ± 1.88 31.81 ± 3.31

Table 2 compares the composition of the Gramineae / L. mixture according to Example 1 of the present invention with a composition containing only a ginger extract (Comparative Example 6) and a composition containing only a Ginger extract (Comparative Example 7) as a comparative example.

In Table 2, Acabos is a representative alpha-glucosidase inhibitor developed by Bayer, Germany in 1977.

As shown in Table 2, Comparative Example 6 (extract of Gramineae) inhibited alpha-glucosidase by 44.4% at a concentration of 100 mu g / mL, which showed similar effects to acarbose, whereas Comparative Example 7 Glucosidase inhibitory effect was not exhibited. In addition, the alpha-glucosidase inhibitory effect was similar to that of the ginger extract alone, and the alpha-glucosidase inhibitory effect was not found when the ginger extract and the yuzu extract were mixed.

PPARγ agonist effect of extract

Table 3 is a table showing the differentiation rate of adipocytes according to the mixed extract of Ganoderma lucidum / Yeoju.

Concentration of extract (/ / mL) Differentiation rate of adipocyte (%) Comparative Example  6 Comparative Example 7 Example 1 Rosiglitazone 100 no effect 60.73 ± 1.17 112.54 + - 3.72 323.53 + - 0.71 50 no effect 42.97 + - 6.73 78.79 ± 1.60 269.24 ± 1.88 25 12.12 ± 0.80 32.75 + - 2.66 72.51 + - 1.70 259.97 + - 7.77 12.5 24.36 + - 4.32 35.60 ± 3.68 18.05 ± 1.95 234.06 ± 0.53 6.25 26.51 ± 1.18 6.00 + - 5.33 29.94 + - 6.49 245.47 ± 5.75

Table 3 compares the composition of the present invention with that of the gruel / lute juice extract according to the present invention, using a composition containing only a ginger extract (Comparative Example 6) and a composition containing only a ginger extract (Comparative Example 7) as a comparative example.

In Table 3, Rosiglitazone is Avandia ™ (the active ingredient loggitazone), which is marketed as a diabetic drug developed by the GlaxoSmithKline Pharmaceutical Company of the United Kingdom.

As shown in Table 3, in Comparative Example 6 (extract of Ganoderma lucidum) did not show any effect on adipocyte differentiation, Comparative Example 7 (extract of Yejoo) increased the adipocyte differentiation rate by 60.73% at 100 ㎍ / mL concentration as compared with the control group . In addition, Example 1 (ginseng / Yejoo mixed extract) showed 85.3% (112.54%) enhancement of adipocyte differentiation compared with Yeoju extract alone.

Given that the positive differentiation of rosiglitazone in adipocytes is 323.53%, the efficacy of Example 1 (ginseng / Yejoo mixed extract) was reduced by 65.2%.

In addition, it was found that Avandia ™ (active ingredient roglitazone), which is commercially available as a diabetic drug, has a high ability to differentiate into adipocytes and thus has an effect as a PPARγ agonist. As a result, Example 1 . ≪ / RTI >

Therefore, the extracts of Ganoderma lucidum and Ganoderma lucidum / Yeoju have inhibitory effect on alpha - glucosidase, and the extracts of Ganoderma lucidum and Ganoderma lucidum / Day and the activity to increase PPARy at the same time.

Effect of Extract on Diabetes

Table 4 is a table showing the diabetic improvement effect according to the gingko extract / Yeoju mixture extract.

division Postprandial glucose
(mg / dL) Weight (g) Dietary intake
(g / day) A negative intake
(mL / day) Fasting blood sugar
(mg / dL) Glycosylated hemoglobin  (%) Comparative Example 1 133 ± 9.1 ** 40.3 ± 1.72 ** 4.6 ± 0.30 ** 4.5 ± 0.37 ** 56 ± 11.7 ** 4.1 ± 0.19 ** Comparative Example 2 151 ± 16.7 * 46.0 ± 6.38 ** 3.5 ± 0.27 ** 4.3 ± 0.58 ** 85 ± 12.2 ** 4.2 ± 0.41 Comparative Example 3 219 ± 114.6 36.6 ± 1.71 ** 5.3 ± 0.37 ** 6.2 ± 1.36 ** 99 ± 16.8 ** 5.4 ± 0.80 ** Party
Urine
U
foot
group Comparative Example 4 519 ± 63.6 31.7 ± 1.55 8.3 ± 0.69 13.9 ± 1.34 519 ± 48.8 8.9 ± 0.96 Comparative Example 6 419 ± 69.1 * 30.8 ± 2.65 9.1 ± 0.95 13.6 ± 1.29 399 ± 63.3 ** 7.5 ± 0.78 * Comparative Example 7 452 ± 55.1 31.8 ± 2.98 8.3 ± 0.68 ** 10.9 ± 1.39 408 ± 57.3 ** 7.6 ± 1.01 ** Example 1 392 ± 58.7 ** 32.2 ± 5.12 8.2 ± 0.57 ** 11.6 ± 1.37 382 ± 54.9 ** 7.0 ± 0.75 ** Example 2 365 ± 96.4 33.2 ± 4.98 8.5 ± 0.88 * 11.0 ± 1.56 371 ± 61.3 ** 6.6 ± 0.55 ** Example 3 370 ± 81.9 32.1 ± 5.05 8.3 ± 0.60 ** 11.3 ± 1.29 380 ± 56.8 ** 6.9 ± 0.81 * Comparative Example 5 365 ± 64.6 ** 33.1 ± 2.47 8.3 ± 0.71 ** 10.0 + 1.07 350 ± 58.7 ** 5.2 ± 0.57 ** * p < 0.05, ** p < 0.01

Table 4 shows that the postprandial blood glucose and the negative intake were decreased in all the administration groups as compared to the control group 4 (control group), and in particular, the administration of Example 1 (control group) (Glycyrrhiza uralensis extract) showed better postprandial hypoglycemic effect.

In addition, compared with Comparative Example 4, Comparative Example 6, Comparative Example 7 and Example 1 show a remarkably improved effect on fasting blood glucose content and HbA 1c in serum. Particularly, compared with Comparative Example 6 and Comparative Example 7, the fasting blood glucose level and the glycated hemoglobin level were significantly lower in Example 2 (the mixture of Ganoderma lucidum / Lentinula extract + olive leaf extract) and Example 3 (Lentinus edulis extract + rosemary leaf extract group) Effectively.

Non-Alcoholic Fatty Liver Inhibitory Effect of Extracts

Figure 2 shows the amount of fat accumulation in liver cells in each group.

FIG. 2 is a graph showing changes in the concentration of the extract of Ganoderma lucidum / L. japonica at a concentration of 50 mg / kg, 100 mg / kg (Example 1) and 200 mg / kg.

Referring to FIG. 2, Example 1 decreased the fat accumulation amount of hepatocytes. In particular, Comparative Example 7, which contained only the extract of Yuzu extract, increased the fat accumulation amount of hepatocytes. However, in Example 1, both of the extract of Ganoderma Lucidum and the extract of Yuzu .

In addition, 200 mg / kg of the extract of Ganoderma lucidum / L. japonica showed the most effective reduction of fat accumulation.

Improvement of renal failure in extract

FIG. 3A is a graph showing a change amount of blood urea nitrogen (BUN) in each group, FIG. 3B is a graph showing a change amount of serum creatine according to an extract, FIG. And the amount of uric acid in the urine.

FIGS. 3A to 3C are graphs showing changes in the concentrations of the extracts of Ganoderma lucidum / Ganoderma lucidum at a concentration of 50 mg / kg, 100 mg / kg (Example 1) and 200 mg / kg, and the normal group is a mouse showing no renal failure.

Referring to FIGS. 3A to 3C, Example 1 effectively reduced the concentrations of blood urea nitrogen, creatinine, and uric acid in serum in an animal model of induction of renal failure by cisplatin.

In addition, when 200 mg / kg of the mixed extract of Ganoderma lucidum / L. japonica were consumed, the concentration of blood urea nitrogen, creatine and uric acid in the serum were most effectively reduced.

Effect of extracts on hyperlipemia

Table 5 shows the improvement effect of hyperlipidemia according to the mixed extract of Ganoderma lucidum / L. japonica.

division Triglyceride
(mg / dL) Total cholesterol
(mg / dL) Comparative Example 1 67 ± 9.4 ** 158 ± 6.9 ** Comparative Example 2 64 ± 7.3 183 ± 17.2 ** Comparative Example 3 50 ± 8.7 152 ± 16.9 Party
Urine
U
foot
group Comparative Example 4 137 ± 22.2 277 ± 24.8 Comparative Example 6 103 ± 14.0 * 153 ± 12.1 ** Comparative Example 7 127 ± 17.6 193 ± 20.0 ** Example 1 119 ± 32.2 168 ± 18.4 ** Example 2 92 ± 21.9 144.5 ± 15.3 Example 3 102 ± 25.3 151 ± 13.2 Comparative Example 5 98 ± 10.1 ** 196 ± 11.6 ** * p < 0.05, ** p < 0.01

Referring to Table 5, Compared with Comparative Example 4, Comparative Example 6, Comparative Example 7 and Example 1 showed a remarkably improved effect on total cholesterol and triglyceride contents in serum. In particular, Example 2 and Example 3 effectively reduced total cholesterol and triglyceride compared to Comparative Example 6 and Comparative Example 7.

While the invention has been shown and described with reference to certain preferred embodiments thereof, it will be understood by those of ordinary skill 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. This is possible.

Therefore, the scope of the present invention should not be limited to the described embodiments, but should be determined by the equivalents of the claims, as well as the claims.

Claims (5)

The prevention of diabetes and diabetic complications including a liquid extract or Ligularia fischeri extract and a liquid extract in the form of a lyophilized powder of the liquid extract or a Momordica charantia extract in the form of a lyophilized powder of the liquid extract, In the therapeutic pharmaceutical composition,
The composition is prepared by dissolving the liquid extract or the liquid extract of Olea europaea or the lyophilized powder of Rosemarinus officinalis leaf extract in the form of a lyophilized powder of the liquid extract into 10 Further comprising a weight portion,
The Ligularia fischeri extract and the Momordica charantia extract are controlled to a weight ratio of 9: 1 to 1: 9 to control the inhibition of blood glucose increase,
Wherein the composition increases the expression of GLP-1 (Glucagon-like peptide 1), and a composition for preventing and treating diabetes and diabetic complications.
The method according to claim 1,
Wherein said pharmaceutical composition comprises said scaly extract and said rumen extract in a weight ratio of 3: 7.
The method according to claim 1,
Wherein the pharmaceutical composition is prepared by any one of formulations selected from tablets, capsules, powders, granules, pills, liquids and suspensions.
For prevention of diabetes and diabetic complications including extracts of Ligularia fischeri and liquid extract or liquid extract of Momordica charantia which is in the form of lyophilized powder of the above liquid extract, In a health functional food composition,
The composition is prepared by dissolving the liquid extract or the liquid extract of Olea europaea or the lyophilized powder of Rosemarinus officinalis leaf extract in the form of a lyophilized powder of the liquid extract into 10 Further comprising a weight portion,
The Ligularia fischeri extract and the Momordica charantia extract are controlled to a weight ratio of 9: 1 to 1: 9 to control the inhibition of blood glucose increase,
Wherein said composition increases the expression of GLP-1 (Glucagon-like peptide 1), and prevents diabetes and diabetic complications.
The prevention of diabetes and diabetic complications including a liquid extract or Ligularia fischeri extract and a liquid extract in the form of a lyophilized powder of the liquid extract or a Momordica charantia extract in the form of a lyophilized powder of the liquid extract, A method for preparing a therapeutic pharmaceutical composition,
Extracting the sea tangle with water, an alcohol having 1 to 5 carbon atoms or a mixed solvent thereof at 0 캜 to 90 캜;
Extracting the yeast with water, an alcohol having 1 to 5 carbon atoms or a mixed solvent thereof at 0 캜 to 90 캜 to prepare a yeast extract; And
Preparing a mixture comprising the ginger extract and the ganoderma extract at a weight ratio of 9: 1 to 1: 9; And
(Olea europaea) leaf extract or a liquid extract or a lyophilized powder of rosemary (Rosemarinus officinalis) leaf extract in the form of a powder obtained by lyophilizing the liquid extract or the liquid extract, A step further comprising a weight part
Lt; / RTI &gt;
Controlling the rate of inhibition of the increase in blood glucose by controlling the weight ratio of the above-mentioned ginger extract to the above-
Wherein said composition increases the expression of GLP-1 (Glucagon-like peptide 1).

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