WO2012021014A2

WO2012021014A2 - Composition for preventing or treating diabetes or diabetes complications, containing composite composition of angelicae gigantis radix extract and wild garlic leaves extract as active ingredient

Info

Publication number: WO2012021014A2
Application number: PCT/KR2011/005914
Authority: WO
Inventors: 김명화; 구세광; 예인해; 이한창
Original assignee: 제일약품주식회사
Priority date: 2010-08-11
Filing date: 2011-08-11
Publication date: 2012-02-16
Also published as: WO2012021014A3

Abstract

The present invention relates to a pharmaceutical composition and a dietary supplement composition containing a composite composition comprising an Angelicae gigantis Radix extract and a wild garlic leaves extract. The composite composition comprising an Angelicae gigantis Radix extract and a wild garlic leaves extract of the present invention shows excellent anti-obesity effects , a blood sugar lowering effect, anti-hyperlipidemia, a liver protecting effect and a kidney protecting effect, and thus can be used as a composition for preventing, treating or improving diabetes, and diabetes complications such as diabetic obesity, an increase of blood sugar, hyperlipidemia, hypertension, arteriosclerosis, apoplexy, liver injury, kidney injury, immunosuppression, eye injury, and the like. In addition, the composite composition has excellent anti-obesity effects, and thus can be used as a composition for preventing, treating or improving obesity.

Description

【Specification】

[Name of invention]

Composition for the prevention or treatment of diabetes or complications of diabetes mellitus containing a complex composition of Angelica extract and acid garlic extract as an active ingredient

Technical Field

The present invention relates to a composition for preventing or treating diabetes mellitus or diabetic complications comprising a composite composition of Angelica extract and acid garlic extract as an active ingredient.

Background Art

Diabetes is one of the representative chronic adult diseases. Diabetes patients in Korea are estimated to be at least 2.5 million, about 5% of the total population.

Diabetes is a disease in which sugar in the blood remains in the blood and cannot be used as energy due to lack of insulin secretion or lack of insulin action or function. The causes of diabetes include westernization of diet, obesity, lack of exercise, and stress. Currently, developed countries such as the United States, Europe, and Japan have tremendous socio-economic consequences of increased obesity and diabetes.In Korea, economic development has led to a rapid increase in diabetes, with more than 300 million patients by 2025. (Kim, Y., Diabetes Care, 1995, 18: 545-548). Diabetes can be broadly divided into insulin-dependent type 1 diabetes and non-dependent type 2 diabetes. Type 1 diabetics rarely secrete insulin due to genetic causes or viral infections, and type 2 diabetics have normal amounts of insulin. In many cases, type 2 diabetes with obesity is caused by insulin resistance caused by an increase in fatty acids in the blood, resulting in abnormalities in glucose metabolism, resulting in higher blood glucose in the blood. It is also thought that abnormalities in insulin secretion and abnormal signal transduction are causes of type 2 diabetes. Insulin resistance is a major factor in the etiology of type 2 diabetes, which appears in more than 90% of people with type 2 diabetes and is thought to precede years of hyperglycemia (Haffner SM, et al. JAMA, 1990, 263: 2893-). 2898). Insulin resistance and thus a combination of metabolic and vascular abnormalities are called insulin resistance syndrome or metabolic syndrome. Insulin Resistance and Metabolic Syndrome It is associated with an increased risk of coronary artery disease, especially coronary artery disease (Isomaa B, et al. Diabetes Care, 2001, 24: 683-9), and metabolic syndrome is reported to triple the risk and mortality of coronary artery disease. (Lakka H, et al. JAMA, 2002, 288: 2709-2716). Metabolic syndrome refers to a condition in which various diseases such as diabetes, hypertension, hyperlipidemia, obesity, coronary or arteriosclerosis, which occur due to chronic metabolic disorders, occur simultaneously. Reaven (Reaven GM, Diabetes, 1988, 37 (1595-1607) for the first time. Metabolic syndrome is characterized by insulin resistance, hypertension, dyslipidemia, and mostly accompanied by overweight or obesity. Metabolic syndrome is also a risk factor for cardiovascular disease and has been reported to be associated with death from all causes. Unlike the type 1 diabetes, the type 2 diabetes patients are reported to have a higher prevalence of metabolic syndrome, and it is known that mortality increases when the patients with type 2 diabetes are accompanied by metabolic syndrome (Bonora E, et al. Diabet Med., 2004, 21: 52-8; Ford ES, Diabetes Care., 2005, 28: 1769-78; Alexander CM, et al. Diabetes, 2003, 52: 1210-1214). In addition, studies have been published on the association between the major and microvascular complications of crab type 2 diabetes and the components of metabolic syndrome such as hypertension and dyslipidemia (Mykkanen L, et al. Diabetologia., 1993, 36: 553-559; Haffner SM, et al. Diabetes, 1992, 41: 715-722). The most serious problems of metabolic syndrome are the development of chronic complications such as diabetic retinopathy, nephropathy, neuropathy, hyperlipidemia, and cardiovascular diseases (stroke, angina, myocardial infarction, peripheral vascular disease) (Wolf SP, Br Med Bull., 1993 , 49: 642-652). Most of these chronic complications go through an irreversible process once they occur, and until now there is no way to completely block this process, which can lead to serious symptoms and death if not properly treated. Therefore, in order to effectively manage or treat metabolic syndrome with complex symptoms, it is ideal to have a hypoglycemic effect to maintain normal blood sugar and to treat nephropathy, liver disease, hyperlipidemia, etc. They are taking blood sugar lowering, blood pressure lowering, and cholesterically. To herbal composition for the prevention and treatment of conventional diabetes or diabetic complications The composition for the prevention or treatment of obesity and metabolic syndrome (Metabolic Syndrome or Syndrome X) containing a complex extract of Evodiae Fructus, White Root (Imperatae Rhizoma) and Cirrus Unshiu Markovich as an active ingredient It is disclosed in the Republic of Korea Patent Publication No. 2009-0114093, the Republic of Korea Patent Publication No. 2010-0956278 is a composite containing Yeoju, Dongeohacho, phalanges, Sangbaekpi, jeonseuneun root, Hwangjeong, Baekchul, Mcmundong, Cornus, Ginseng Disclosed is a composition for the treatment or prevention of diabetes or diabetic complications using the herbal extract as an active ingredient.

In addition, Korean Patent Publication No. 2006-0025990 discloses Baekgangjam, Red Ginseng, Pageukcheon, Donkey God, Gugija, Bokbunja, Jahanggi, Breeding, Gupan, Keel, Choeyang, Hwangjeong, Jiji, Gokjeongcho, Dragon Meat, Sujijihwang, Wooseol, Blush Disclosed is a composition for preventing diabetes light containing a complex herbal extract consisting of a powder, aspirations, schisandra, baekpanxin, fasting, itinerary, chajeonja, antler, hippocampus, and clam.

Furthermore, Korean Patent Laid-Open Publication No. 2003-0059952 discloses a composition comprising an extract consisting of a peritropic excipient pure herbal medicine compound, ie, rhubarb, tea, earth and sand, fruit, wind and poison.

However, there is still a need for the development of substances that can more effectively prevent or treat diabetes or diabetes complications. Angelica gigas Nakai is a naturalized plant that is cultivated in Korea, and the Korean Angelica is known as a true donkey. It is a perennial herb that is native to Japan and is 60-90 cm high, and its flowers are white in August-September. Running at the end, the fruit is flat long oval with narrow wings at the edge. The root is called Angelica, which has the effect of blood, so there is no blood on the face, dizziness is frequent, and it is known to be effective for people who have no gloss on eyes and lips. Head weakness of the body, women's menstrual control is excellent because it is often used in various prenatal or postpartum diseases, and it cures menstrual irregularities and abdominal pain. It is effective in treating constipation due to weak gastrointestinal function (Bae-Hwan Bae, Health guidebook based on folk remedies and herbal remedies, 2003, 102-103).

As far as is known, coumarine-based decursin, decursinol, decursinol, nodakenetin, umbel liferon, and nodakenin Beta-sitosterol, angelan-I and angelan-Π. Isolated decusin and decosinol have been shown to paralyze the rabbit extraction intestine, inhibit the frog extraction heart, and breathe rabbit Inhibition and hypotension have been reported, and there have been reports of inhibition of spontaneous action in mice (Journal of Pharmacognosy 1970, 1, 1: 25-32). In addition, antithrombotic action, hematopoietic action, cardiac contractile action, vascular relaxation action, atherosclerosis suppression effect through lowering blood lipid concentration, immunomodulation action, anticancer action and anti-inflammatory action have been reported (Chung BS, et. al,

Hyangyak Daesacheon: Youngrimsa, 1998, 406-408. Recently, it has been found that decusin enhances the activity of protein kinase C, and pectin polysaccharides Angelan-I and Angelan-Π are effective as anticancer agents or immune enhancers (Korean Patent Publication). No. 1999-0031277), as a nephrotoxic inhibitor that can effectively reduce the renal toxicity, it has been reported that it can be particularly useful in anticancer drugs or diabetes therapeutic composition (Korean Patent Publication No. 2001-0080265).

In addition, Angelica extracts were induced by diabetes by promoting the activation of 5 'AMP-activated protein kinase (AMP') and glucose uptake in the C2C12 myotube, a mouse skeletal muscle cell. It has been reported that various diseases can be prevented (Korean Patent Publication No. 2005-0111657), and lipid metabolism is improved to decrease blood concentration of trigyceride and increase blood concentration of HDL cholesterol in diabetic disease. It is also known to work (Korean Patent Publication No. 2009-0078267). Mountain garlic (Allium victor ial is subsp.platyphyl lum) is a perennial herb belonging to the monocotyledonous liliaceae, which is distributed throughout the region. The extract of each part of mountain garlic is edible and has been traditionally used in one room for cold, antibacterial, digestive and dry stomach. In addition, sulfur compounds with potential antithrombotic action and antiplatelet cell activity have been reported (Wijaya, CH et al., Nat. Prod. Sci., 1996, 2, 37-42; Li akopou 1 ou-Kyr i ak i des, M. et al., Phytochem., 1985, 24, 600-601). In addition, the effects of the acid garlic extract has been widely studied, the composition for the prevention or treatment of atherosclerosis and hypercholesterolemia containing acid garlic extract as an active ingredient (Korean Patent Publication No. 2002-0050362), liver protection or Compositions for the prevention or treatment of liver disease (Korea Patent Publication No. 2005-0102572), compositions for the prevention or treatment of diabetic disease (Korea Patent Publication No. 2005-0043092), and the like have recently been reported. Antimicrobial composition (Korean Patent Publication No. 2009-0100732), restoring the inhibition of gap junctional intercellular communication (GJIC), a pathology that occurs during cancer development or progression, to prevent cancer or Therapeutic composition Water (Korean Patent Publication No. 2009-0100573) and the like have been reported. Accordingly, the present inventors have studied to find an effective substance for diabetic or diabetic complications in natural products, and as a result, a composite composition of a mixture of Angelica extract and acid garlic has a synergistic effect than the sum of the individual extracts to treat and improve diabetes or diabetic complications. Confirmed to exhibit an excellent effect to complete the present invention.

[Detailed Description of the Invention]

[Technical problem]

An object of the present invention to provide a pharmaceutical composition for the prevention or treatment of diabetes mellitus or diabetic complications containing a complex composition of the Angelica extract and acid garlic extract as an active ingredient.

Another object of the present invention to provide a pharmaceutical composition for the prevention or treatment of obesity diseases containing a complex composition of Angelica extract and acid garlic extract as an active ingredient.

Another object of the present invention to provide a health food composition for the prevention or improvement of diabetes mellitus or diabetic complications containing a complex composition of the Angelica extract and acid garlic extract as an active ingredient.

Another object of the present invention to provide a health food composition for the prevention or improvement of obesity diseases containing a complex composition of Angelica extract and acid garlic extract as an active ingredient.

Technical Solution

In order to achieve the above object, the present invention provides a method for preventing diabetes or diabetic complications comprising a composite composition in which the mixed weight ratio of Angelica extract and acid garlic extract is 1: 4-6 or 2-4: 1 as an active ingredient. Provided is a therapeutic pharmaceutical composition.

In another aspect, the present invention provides a pharmaceutical composition for the prevention or treatment of obesity diseases containing a complex composition of the mixed weight ratio of Angelica extract and acid garlic extract 1: 1: 6-6 or 2-4: 1 as an active ingredient. .

Furthermore, the present invention is a health food composition for preventing or improving diabetes or diabetic complications containing a composite composition of the mixed weight ratio of Angelica extract and acid garlic extract is 1: 4-6 or 2-4: 1 as an active ingredient To provide. In addition, the present invention provides a health food composition for the prevention or improvement of obesity diseases containing a complex composition of the mixed weight ratio of Angelica extract and acid garlic extract 1: 4-6 or 2-4: 1 as an active ingredient. .

Advantageous Effects

In the case where the composition ratio of the composite composition of Angelica extract and acid garlic extract according to the present invention is 1: 4-6 or 2-4: 1, better anti-obesity, hypoglycemia, and anti-obesity than the sum of the effects of the individual extracts Prevents, treats or improves diabetic and diabetic obesity, hyperglycemia, hyperlipidemia, hypertension, atherosclerosis, stroke, liver damage, kidney damage, immunosuppression, eye damage It can be usefully used as a composition for the composition, and because it is excellent in anti-obesity effect, it can be usefully used as a composition for preventing, treating or improving obesity.

[Brief Description of Drawings]

1 is a graph showing the weight gain for the administration group according to an embodiment of the present invention.

Figure 2 is a view showing the change in the diameter of the ovarian peripheral fat cells and abdominal wall fat cells diameter for the administration group according to an embodiment of the present invention.

[Best form for implementation of the invention]

The present invention provides a pharmaceutical composition for preventing or treating diabetic or diabetic complications, which contains a complex composition of the Angelica extract and acid garlic extract as an active ingredient.

Hereinafter, the present invention will be described in detail. In the pharmaceutical composition according to the present invention, the Angelica extract and the garlic extract is preferably a weight ratio of 1: 4-6 or 2-4: 1, more preferably 1: 4 or 4: 1, Most preferred is 4: 1. In addition, the pharmaceutical composition according to the present invention exhibits anti-obesity activity, and thus may be usefully used for preventing or treating diabetic obesity disease, which is a complication from diabetes. Specifically, the effects of the pharmaceutical composition according to the present invention on the body weight, changes in the ovarian fat weight, changes in the ovarian fat cell diameter and changes in abdominal wall fat cell diameter, weight loss, ovary It has excellent effects on reducing peripheral fat weight, decreasing ovarian fat cell size, and reducing abdominal wall fat cell size, and thus can be usefully used for preventing or treating diabetic obesity diseases (see Examples 1 and 6 and FIGS. 1-2). . Furthermore, the pharmaceutical composition according to the present invention exhibits hypoglycemic activity, and thus may be useful for preventing or treating diabetes or complications caused by diabetes.

Specifically, as a result of performing an experiment on the effect of the pharmaceutical composition on the blood sugar according to the present invention, since the effect of lowering blood sugar, it can be useful to prevent or treat diabetes or diabetic complications (Example 2 And 7). In addition, the pharmaceutical composition according to the present invention exhibits anti-hyperlipidemic activity, and thus may be useful for preventing or treating diabetes or complications caused by diabetes.

Specifically, experiments were performed to measure changes in total cholesterol and blood triglyceride content, low blood density lipoprotein (LDL) and high density lipoprotein (HDL) content in blood for the pharmaceutical composition according to the present invention. Results: decreased total cholesterol in blood, decreased blood triglyceride content, decreased blood LDL content and increased HDL content in blood (see Examples 3 and 8), increased number of pancreatic islets, increased pancreatic islet diameter and pancreatic islet. As the number of endogenous glucagon immune response cells decreases, the protective effect against pancreatic B cells (see Example 11) is excellent, and thus can be useful for preventing or treating diabetes or diabetic complications. Furthermore, the pharmaceutical composition according to the present invention may be useful for preventing or treating diabetes mellitus or complications caused by diabetes by showing liver protective activity.

Specifically, as a result of experiments for measuring the change in liver weight of the pharmaceutical composition according to the present invention, the change in the content of aspartame aminotransferase (AST) and alanine aminotransferase (ALT) in the blood, the liver weight increase , Blood AST content decrease and blood ALT content Its excellent reducing effect can be used to prevent or treat diabetes or diabetic complications (see Examples 4 and 9). In addition, the pharmaceutical composition according to the present invention exhibits renal protective activity and can be usefully used for preventing or treating diabetes or complications caused by diabetes.

Specifically, as a result of the experiment to measure the change in the blood urea nitrogen (BUN) and creatinine content and the change in the number of denatured tubules for the pharmaceutical composition according to the present invention, reduced blood BUN content, reduced blood creatinine content, degeneration It is excellent in reducing the number of tubules and reducing the kidney weight, and thus can be usefully used for preventing or treating diabetes or diabetic complications (see Examples 5, 10 and 12). Furthermore, the pharmaceutical composition according to the present invention can be usefully used for preventing or treating diabetes or complications caused by diabetes by showing an immunoactive effect.

Specifically, 가슴 change of thymus gland weight, change of spleen weight, change of total thickness of thoracic lobule, change of thickness of thyroid cortex, change of total thickness of spleen for the pharmaceutical composition according to the present invention As a result of experiments to measure the change, the weight of the thymus gland increased, the spleen weight increased, the total thickness of the thymus lobules, the thickness of the thymus cortex increased, the total thickness of the spleen, and the mean diameter of the splenic white medulla. It can be usefully used to prevent or treat complications (see Example 13). In addition, the pharmaceutical composition according to the present invention exhibits an ocular protective activity, and can be usefully used for preventing or treating diabetes or complications caused by diabetes.

Specifically, the change of the cataract visual acuity, the change of the cataract quantitative image value, the change of the lens damage value, the change of the thickness of the lens damage region, the change of the total thickness of the retina, the frozen layer in the retina Experiments measuring the change in thickness, the thickness of the nuclear layer in the retina, and the number of hematopoiesis present in the perilimbary membrane resulted in decreased cataract visual acuity, quantitative cataract image, decreased lens injuries, and lens injuries. Decreased thickness of the area ， increased total thickness of the retina ， frozen Since it is excellent in increasing the thickness of the base layer, increasing the thickness of the nucleus in the retina and reducing the number of blood cells present in the inner boundary membrane, it can be usefully used for preventing or treating diabetes or diabetic complications (see Example 14). Therefore, the composite composition of the Angelica extract and acid garlic extract of the present invention shows a very excellent effect in obesity, diabetes mellitus, hyperglycemia, liver damage, kidney damage, immune activity and eye protection caused by diabetes or diabetes. Therefore, it can be usefully used for diabetes or diabetic complications. Furthermore, the diabetes which can be prevented or treated by the pharmaceutical composition according to the present invention is type 2 diabetes, and the diabetic complications include diabetic nephropathy, diabetic liver cirrhosis, hypertension, atherosclerosis, stroke, Heart failure, immunosuppression and diabetic retinopathy may be further included. The present invention also provides a method for treating diabetes mellitus or diabetic complications comprising the step of administering an effective amount of the composite composition of the Angelica extract and acid garlic extract to a subject in need thereof. In the treatment method according to the present invention, the Angelica extract and the garlic extract is preferably a weight ratio of 1: 4-6 or 2-4: 1, more preferably 1: 4 or 4: 1, 4: Most preferably, it is 1. In addition, in the treatment method according to the present invention, the complex composition exhibits an anti-obesity effect by reducing weight, reducing ovarian peripheral fat weight, decreasing ovarian peripheral fat cell size, and reducing abdominal wall fat cell size. Complications caused by treatment can be treated (see Examples 1 and 6 ′ FIGS. 1-2). Furthermore, in the treatment method according to the present invention, the complex composition exhibits a hypoglycemic effect, thereby treating diabetes or complications caused by diabetes (see Examples 2 and 7). In addition, in the treatment method according to the invention, the complex composition is hypercholesterol total cholelate It has been shown to decrease sterol content, blood triglyceride content, and blood low density lipoprotein (LDL) content, and increase blood high density lipoprotein (HDL) content (see Examples 3 and 8). Since the diameter is increased and the number of glucagon immune response cells in the pancreatic islets is excellent, the protective effect against pancreatic B cells (see Example 11) is excellent, thereby treating complications caused by diabetes or diabetes. Furthermore, in the treatment method according to the present invention, the complex composition exhibits a hepatoprotective effect by reducing liver weight, decreasing blood aspartame aminotransferase (AST) content and decreasing blood aminotransferase (ALT) content. , Diabetes or complications caused by diabetes can be treated (see Examples 4 and 9). In addition, in the treatment method according to the present invention, the complex composition exhibits a renal protection effect by reducing the content of urea nitrogen (BUN) and creatinine in the blood, reducing the number of denatured tubules, and reducing kidney weight. Diabetes or complications caused by diabetes can be treated (see Examples 5, 10 and 12). Furthermore, in the treatment method according to the present invention, the complex composition is effective in increasing the thymus gland weight, increasing the spleen weight, increasing the total thickness of the thymus lobule, increasing the thickness of the thyroid cortex, increasing the total thickness of the spleen, and increasing the mean diameter of the splenic white medulla. By exhibiting an active effect, diabetes or complications arising from diabetes can be treated (see Example 13). In addition, in the treatment method according to the present invention, the composite composition is a cataract visual acuity reduction, cataract quantitative image number reduction, lens damage value reduction, lens damage area thickness reduction, retinal thickness increase, retinal freezing layer thickness increase And an increase in the thickness of the nuclear layer in the retina and a decrease in the number of hematopoiesis present in the inner layer of the membrane, thereby exhibiting an ocular protective activity, thereby treating complications caused by diabetes or diabetes (see Example 14). Therefore, in the treatment method according to the present invention, the composite composition of the Angelica extract and wild garlic extract of the present invention is a combination of diabetes mellitus or diabetes mellitus obesity, increased blood sugar, hyperlipidemia, liver damage, kidney damage, immune activity and eye Very good in protection Because of its numerous effects, it can treat diabetes or diabetic complications. The present invention also provides a pharmaceutical composition for the prevention or treatment of obesity diseases, containing a complex composition of the Angelica extract and acid garlic extract as an active ingredient.

In the pharmaceutical composition according to the present invention, the Angelica extract and the garlic extract is preferably a weight ratio of 1: 4-6 or 2-4: 1, more preferably 1: 4 or 4: 1, 4: 1 is most preferable.

As described above, the pharmaceutical composition of the present invention is excellent in weight loss, peripheral ovarian fat weight reduction, ovarian fat cell size reduction, abdominal wall fat cell size reduction effect, so as well as diabetic obesity diseases caused by diabetes, It can be useful for preventing or treating obesity diseases. In another aspect, the present invention provides a method for treating obesity diseases comprising the step of administering to the subject in need thereof a complex composition comprising a mixture of the Angelica extract and acid garlic extract.

In the treatment method according to the present invention, the Angelica extract and acid garlic extract is preferably a weight ratio of 1: 4-6 or 2-4: 1, more preferably 1: 4 or 4: 1, 4: Most preferably, it is 1.

In addition, in the treatment method according to the present invention, the complex composition exhibits an anti-obesity effect by reducing the weight, decreasing the ovarian fat weight, reducing the size of the peripheral fat cells, reducing the size of the abdominal wall fat cells, thereby producing obesity diseases. Can be treated (see Examples 1 and 6, FIGS. 1-2). Furthermore, the present invention provides a health food composition for preventing or improving diabetic or diabetic complications, which contains a complex composition of the Angelica extract and acid garlic extract as an active ingredient.

In the health food composition according to the present invention, the Angelica extract and the acid garlic extract is preferably a weight ratio of 1: 4-6 or 2-4: 1, more preferably 1: 4 or 4: 1. 4: 1 is most preferable. In addition, the health food composition according to the present invention shows a weight loss, ovarian fat weight reduction, ovarian fat cell size reduction, abdominal wall fat cell size reduction effect Since it appears to have a fish tank obesity effect, it can be usefully used to prevent or ameliorate diabetes or diabetes-caused complications (see Examples 1 and 6 and FIGS. 1-2). Furthermore, since the health food composition has been shown to have a hypoglycemic effect, it may be usefully used for preventing or improving complications caused by diabetes or diabetes mellitus (see Examples 2 and 7). In addition, the health food composition has a blood total cholesterol content, blood triglyceride content, blood low density lipoprotein (LDL) content reduction effect, blood high density lipoprotein (HDL) content increase effect (Examples 3 and 8) ), The number of pancreatic islets, the diameter of the pancreatic islets, and the number of glucagon immune reaction cells in the pancreatic islets are reduced, so the protective effect against pancreatic B cells is excellent (see Example 11). It can be usefully used for prevention or improvement. Furthermore, the health food composition shows a liver protection effect by reducing liver weight, decreasing blood aspartameaminotransferase (AST) content and decreasing blood aminotransferase (ALT) content, which is caused by diabetes or diabetes mellitus. It can be usefully used to prevent or ameliorate complications (see Examples 4 and 9). In addition, the health food composition exhibits a kidney protective effect by reducing the content of urea nitrogen (BUN) and creatinine in the blood, reducing the number of denatured tubules, and reducing kidney height, thereby improving the diabetic or diabetic complications. It can be usefully used to prevent or improve (see Examples 5, 10 and 12). Furthermore, since the health food composition shows an effect of increasing the thymus gland weight, increasing the spleen weight, increasing the total thickness of the thymus lobule, increasing the thickness of the thyroid gland, increasing the total thickness of the spleen, and increasing the mean diameter of the splenic white medulla, It can be usefully used to prevent or ameliorate diabetes or complications caused by diabetes (see Example 13). In addition, the health food composition is a cataract visual acuity reduction, cataract quantitative image Eye protection due to decreased numbers, decreased lens injuries, reduced thickness of the lens injured area, increased retinal thickness, increased thickness of the frozen layer in the retina, increased thickness of the nuclear layer in the retina, and a decrease in the number of blood in the boundary layer. Since it appears to have an active effect, it can be usefully used to prevent or ameliorate diabetes or complications caused by diabetes (see Example 14). Therefore, the composite composition of the Angelica extract and acid garlic extract of the present invention has a very excellent effect in obesity, increased blood sugar, hyperlipidemia, liver damage, kidney damage, immune activity and eye protection caused by diabetes or diabetes. It can be usefully used to improve diabetes or diabetic complications of diabetes mellitus or diabetic complications. Furthermore, the diabetes that can be prevented or improved by the health food composition according to the present invention is type 2 diabetes, and the complications of diabetes include diabetic nephropathy, diabetic liver cirrhosis, hypertension, atherosclerosis, stroke, and heart failure. ， Immunosuppression and diabetic retinopathy may further include. In another aspect, the present invention provides a health food composition for preventing or improving obesity diseases containing a composite composition of the Angelica extract and acid garlic extract as an active ingredient.

In the health food composition according to the present invention, the Angelica extract and the acid garlic extract is preferably a weight ratio of 1: 4-6 or 2-4: 1, more preferably 1: 4 or 4: 1. , 4: 1 is most preferred.

The health food composition of the present invention is excellent in weight loss, peripheral ovarian fat weight reduction, ovarian fat cell size reduction, abdominal wall fat cell size reduction effect to prevent diabetic obesity diseases caused by diabetes as well as normal obesity diseases Or it can be useful for treatment. In addition, the composition according to the present invention exhibits an excellent anti-obesity, antihyperlipidemia, hypoglycemic effect, hepatoprotective effect, renal protective effect and immunoprotective effect depending on the dose.

Furthermore, the composition according to the present invention exhibits an equivalent or better effect than the double-dose control group in the combination-complex group with the control drug, and is superior by the combination of the composition with various other drugs. Anti-obesity It was confirmed that there is a possibility of hypoglycemia, hypoglycemic effect, hepatoprotective effect, renal protection effect, immune activity effect and eye protection effect. In addition, the composition according to the present invention was not recognized as a result of a single oral dose toxicity test in rats up to the limit dose of 2000 mg / kg, the micronucleus test using mouse bone marrow cells was observed to be negative , It was confirmed that the composition is safe for use in health food and food jars (see Examples 15 and 16). In the composite composition containing the Angelica extract and acid garlic extract according to the present invention, the Angelica and acid garlic can be used without limitation, such as cultivated, harvested or commercially available. The donkey and mountain garlic can use the entire plant, preferably using a leaf, stem or root, but is not limited thereto. The Angelica and live garlic can be used at any stage of the growth stage.

Extraction solvents for extracting Angelica and oleracea are preferably water, alcohols or mixtures thereof, preferably water, lower alcohols of d ₄ , or mixtures thereof, and it is more preferable to extract methane or ethanol. Preferably, but not limited to.

The amount of the extraction solvent is preferably 2-30 times the dry weight of Angelica and dry garlic, and more preferably 20 times, but is not limited thereto.

The method of extracting the Angelica extract and acid garlic extract is a method using an extraction device such as hot water extraction, dipping extraction, supercritical extraction, subcritical extraction, high temperature extraction, high pressure extraction, reflux angle extraction and ultrasonic extraction or XAD and HP Conventional extraction methods in the art can be used, such as the use of adsorption resins containing -20, and is preferably heated, reflux extraction or phase extraction from, but is not limited thereto. Extraction times of the sugar ear extract and the garlic extract is preferably 1-5 times, more preferably three times repeated extraction is not limited thereto. It may be extracted once -5 times by the ultrasonic extraction method. Silver extraction is preferably 10 ^° C-100 ^° C and more preferably room temperature, but is not limited thereto. The extraction time is preferably 1 day -7 days, more preferably 3 days -7 days, but is not limited thereto.

Concentration under reduced pressure after extraction is preferred, but is not limited thereto.

At this time, the vacuum concentration is preferably a vacuum rotary evaporator, but is not limited thereto. In addition, the drying is vacuum drying, boiling drying, spray drying, It is preferable to perform warm or lyophilization, but not always limited thereto. Specifically, the composite composition according to the present invention may be prepared in powder form by concentrating under reduced pressure at a temperature of 60-70 ^° C, or by lyophilization or drying using a spray dryer or fluid bed granulator. The composition comprising the Angelica extract and acid garlic extract of the present invention preferably comprises 0.1-50% by weight of the composition relative to the total weight of the composition, but is not limited thereto. The composite composition of the Angelica extract and acid garlic extract according to the present invention may further include a suitable carrier, excipient and diluent commonly used in the manufacture of a medicament.

The composition according to the present invention can be used in the form of oral formulations, external preparations, suppositories, and sterile injectable solutions, such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, respectively, according to conventional methods. Can be. Carriers, excipients and diluents which may be included in the compositions of the present invention include lactose, dextrose, sucrose, sorbbi, manny, xylly, erythri, malty, starch, acacia rubber, alginate, gelatin, Calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyridone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. have.

In the case of formulation, it is prepared by using commonly used layering agents, extenders, binders, wetting agents, disintegrating agents, and diluents or excipients. High brothers for oral administration include tablets, pills, powders, granule capsules, and the like, and such solid preparations include at least one excipient in the composition of the present invention, for example, starch, calcium carbonate, sucrose It is prepared by mixing sucrose, lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups. In addition to commonly used simple diluents, water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives can be included. have. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as evolved oil, and injectable esters such as ethyl oleate. Can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerin gelatin and the like can be used. The compositions of the present invention may be administered orally or parenterally, for example, orally, sublingually, nasal, rectally or subcutaneously.

Preferred dosages of the compositions of the present invention vary depending on the condition and weight of the patient, the severity of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the composition of the present invention may be administered in divided doses -3 times a day within the range of 10-1000 mg dose based on the normal person (standard weight 60 kg), but is not necessarily limited thereto. The amount does not limit the scope of the present invention in any aspect. The composite composition combining the Angelica extract and acid garlic extract according to the present invention may be added to the health supplements such as food, beverages and the like for the purpose of preventing or improving diabetes disease, diabetes complications or obesity.

There is no particular limitation on the kind of food. Examples of foods to which the above substances can be added include dairy products, including soups, meat sausages, breads, biscuit cakes, chocolate candy snacks, confectionery, pizza, ramen, other noodles, ¾, ice creams, various soups, beverages , Alcoholic beverages, dairy products and dairy products, and the like, and may include all of the health functional foods in the conventional sense.

Angelica extract and acid garlic extract of the present invention may be added to the food as it is, or used with other food or food ingredients, and may be appropriately used according to conventional methods. The mixing amount of the active ingredient can be suitably determined according to the purpose of use (prevention or improvement). In general, the amount of the composite composition in the health food can be added to 0.1-90 parts by weight of the total food weight. However, in the case of long-term intake for health and hygiene or health control purposes, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.

The health functional beverage composition of the present invention is not particularly limited to other ingredients except for containing the complex composition as essential ingredients in the indicated ratios, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. . Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disa Carbides such as maltose, sucrose and the like; And sugars such as conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like, and xylitol, sorbitol, erythritol and the like. As flavoring agents other than those mentioned above, natural flavoring agents (tautin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 mi of the composition of the present invention.

In addition to the above, the Angelica extract and acid garlic extract of the present invention are various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors such as flavoring agents, coloring agents and neutralizing agents (cheese, chocolate, etc.), pectic acid And salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks and the like. In addition, the Angelica extract and acid garlic extract of the present invention may contain a pulp for the production of natural fruit juice and fruit juice beverage and vegetable beverage.

These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected in the range of 0.1 to about 20 parts by weight per 100 parts by weight of Angelica extract and acid garlic extract of the present invention.

[Form for implementation of invention]

Hereinafter, the present invention will be described in detail by production examples and examples.

However, the following Preparation Examples and Examples are merely to illustrate the present invention, the content of the present invention is not limited to the following Preparation Examples and Examples.

Preparation Example 1 Preparation of Angelica Extract and Mountain Garlic Extract

In this experiment, Angelica gigas (Angelica Gigas Radix) was collected from Pyeongchang, Gangwon-do, and Wild Garlic Leaves were used from Namwon, Jeollanam-do. First, 50% ethane was added to 100 g of the Angelica and 50 g of garlic, and 2.7 mg of the Angelica was extracted using a water bath (East-West Science DS—SWB-4) for 3 hours at 60 ° C. Garlic was extracted at 80 ° C for 3 hours, and the filtrate was filtered under reduced pressure using a filter paper to obtain a concentrate using a vacuum evaporator (BUCHI Rotavapor R— 144, swizerland). Got. As a result, Angelica obtained 32 g of lyophilized extract in 32% yield and 10.8 g of acid garlic in 18% yield. The freeze-dried extract powder is 10 mg / mi concentration in distilled water Were dissolved and stored in a -20 freezer, light brown and dark brown, respectively, shielded from light and denaturation.

Example 1 Effect of Complex Composition Composed of Angelica Extract and Mountain Garlic Extract on Obesity

Preparation of Animal Models of Diabetes

The mice fed high fat diet (HFD) prepared to investigate the anti-obesity, hypoglycemia, anti-hyperlipidemia, hepatoprotective and renal protective effects of diabetic or diabetic complications of the Angelica extract and acid garlic extract of the present invention are diabetic and As the most widely used animal model for developing related metabolic syndrome therapies (Sone H et al., Trends Mol Med. 2001, 7: 320-2; Park SH et al., J Ethnopharmacol., 2005, 102: 326-35) , It is known that obesity is caused by high fat feeding, and in general hyperglycemia, insulin resistance, fatty liver, kidney degeneration and hyperlipidemia (Surwit RS et al., Diabetes., 1988, 37: 1163-7; Thupari JN et al., Aw J Physiol Endocrinol Me tab. 2004, 287-97-E104; Yun SN et al., Arch Pharm Res., 2004, 27: 790-6). In the present invention, a total of 18 groups (126 horses) were used, with 7 mice per group as one group, and the group fed normal rodent feed (superfeed Co., Korea) and the 45 / Kcal high fat feed. (D12451; Diet reserch, PA, USA) divided into groups (Control) fed. During the experiment, the feed and water were freely ingested during the day, the animal room was kept at a temperature of 20-25 ^° C, the humidity was maintained at 40-45 ^° C, and the day and night were repeated every 12 hours. It was used after adjusting the light-dark cycle. The components of the general feed and high fat feed are described in Table 1 below. Table 1

Preparation of Test Substance

A total of 11 kinds of composite compositions were prepared by mixing the Angelica extract and acid garlic extract of the preparation example in the weight ratio of Table 2.

Simvastatin (Wha Pharm. Ind. Co., Ltd., Korea), silymarin (Sigma, MO, USA), metformin (Wako Pure Chemical, Osaka, Japan) were used as control drugs. The reference drug was kept in a block so that light and moisture were blocked.

Table 2

Administration of Test Substance

The prepared composite composition was used directly dissolved in distilled water, high fat feed After 1 week, 7 animals per group were divided into 18 groups and orally administered at 10 / kg once a day for 84 days. Eleven complex compositions and two single extracts were administered at 100 mg / kg and simvastatin, silymarin and metformin at 10 100 250 mg / kg, respectively. At the end of drug administration, two animals with large standard deviations of body weight were excluded from each group. Table 3 shows the composition and administration group of the substances together.

[Table 3]

In all high fat feed (HFD) feeding groups of the present invention, the weight intake was significantly reduced compared to the normal control group. However, in terms of calories, the calorie (4.73 kcal / g) of the high fat feed used in this experiment was the normal feed (0.21). kcal / g) is approximately 20 times higher (see Table 1), so it does not seem to have a significant effect on the induction of obesity.

In addition to the significant increase in feed intake in the sub-composite-administered group, no significant change in feed intake compared to the HFD control group was observed in all the administered groups, so the pharmacological effects recognized in the present invention were not due to reduced feed intake. It is judged. Effect of Complex Composition of Angelica Extract and Mountain Garlic Extract on Obesity Fat accumulation is the most common phenomenon caused by obesity and is known to cause fat cell hypertrophy during histopathological examination (DiGirolamo M et al., Physiol , 1998, 274: R1460-7; Morange PE et al., Arterioscler Thromb Vase Biol., 2000, 20: 1150-4). Adipose tissue is an organ that performs both endocrine and secretion as well as a simple energy store, and is known to secrete adipokine, a bioactive substance secreted from adipocytes (Fuji ta H et al., Endocr). J. 2005, 52: 427-33). Changes in the secretion of adipokine are known to lead to complex diseases such as obesity and insulin resistance (Mitchell M et al., Reproduction., 2005, 130: 583-97).

(1) effect on weight

In order to examine the effect of the composite composition consisting of Angelica extract and acid garlic extract of the present invention on obesity, the weight change of the mice administered the composite composition is shown in Figure 1 and Table 4.

Table 4

Weight gain

Classification Hero Period Duration HFD Control

% Compared to (7¾) (84)

Control Normal Group 1.56 ± 0.08 3.24 ± 3.94

HFD 4.50 ± 1.77 22.56 ± 7.44 596.30 (relative to normal group) Simvastatin 5.54 ± 3.67 15.76 ± 7.22 -30.14

Reference Drug Silymarin 5.62 ± 3.07 15.50 ± 13.21 -31.29

Administration group metformin 3.58 ± 1.95 9.00 ± 3.00 -60.11

Isolated Angelica 6.16 ± 1.78 12.64 ± 6.86 -43.97

Administered acid garlic 5.70 ± 1.58 13.02 ± 2.39 -42.29

1: 1 4.38 ± 1.49 15.66 ± 8.55 -30.59

Angelica: Wild Garlic 1: 2 5.32 ± 2.24 16.62 ± 7.04 -26.33

1: 4 4.50 ± 0.77 10.34 ± 6.07 -54.17

Compound 1: 6 5 · 18 ± 1 · 32 11.76 ± 4.73 -47.87

Composition 1: 8 3.40 ± 2/78 13.74 ± 1.83 -39.10

Administration group 1:10 4 · 38 ± 0 · 94 13.76 ± 4.10 -39.01

2: 1 5 · 19 ± 1.22 11.81 ± 4.82 -47.65

(mg / mg)

4: 1 5.16 ± 1.28 9.24 ± 3.15 -59.04

6: 1 4.24 ± 1.36 24.36 ± 4.70 7.98

8: 1 5.40 ± 2.41 19.88 ± 2.62 -11.88

10 ： 1 5.72 ± 1.57 16.44 ± 5.99 -27.13

As shown in Table 4, the mice fed the high fat diet used as the high fat diet (HFD) control group gained 596.30% higher body weight than the mice fed the normal diet used as the normal control group. Angelica excluding the group consisting of simvastatin, silymarin and metformin, donkey extract or wild garlic extract alone, and weight gain similar to HFD control group: 6) The combination composition of the extract and the acid garlic extract showed 11.88-54.17% of weight loss compared to the HFD control group, and when the ratio of donkey: acid garlic was 1: 4-6 and 2-4: 1, 47.65—59.04% Remarkably, the weight ratio of the composite composition was 54.17% and 59.04%, respectively, and the weight ratio of the composite composition was excellent. Are shown to be better than the weight loss of the ear when administered alone (43.97%) and garlic acid when administered alone (42.29%) effect.

Particularly, when the weight ratio of Angelicae: Mountain garlic is 4: 1, the weight loss effect was higher than that of HFD control group. The best result was 59.04%, which showed anti-obesity effect. (2) Change of fat weight around the ovary

In order to examine the effect of the composite composition consisting of Angelica extract and acid garlic extract of the present invention on obesity, the experimental results are measured by measuring the change in the fat weight around the ovary of the mice administered the composite composition is shown in Table 5 below It was.

Table 5

As shown in Table 5, the mice fed the high fat feed used as the high fat feed OFD) control group had a 503.32% increase in the weight of the ovary fat compared to the normal fed mice used as the normal control. And donkey chu The group administered with simvastatin, silymarin, and metformin used as a control drug except the composite composition group having a composition ratio of 6: 1 in which the relative composition to the body weight of the extract and the acid garlic extract were increased, the donkey extract or the acid garlic It was confirmed that the fat weight around the ovary was reduced by 24.51-57.58% compared to the HFD control group in the single administration group and the 10 Angelica extract and the composite composition administration group of acid garlic.

When the weight ratio of donkey: acid garlic is 1: 2-6, 2-4: 1 and 10: 1 in the administration group, the weight of fat around the ovary is 38.45-57.58%, which is more than that of the Angelica extract or the acid garlic extract alone. Among them, the weight ratio of the composite composition was 54.28% and 57.58% in the group of 1: 4 and 4: 1, respectively, and the ovarian fat weight reduction was excellent. And when it was administered alone with the garlic (29.54%) was found to be much better than the ovarian fat weight reduction effect.

Particularly, when the weight ratio of donkey: acid garlic was 4: 1, it was confirmed that the weight loss effect around the ovary was the best as 57.5¾ compared to the control group, which showed anti-obesity effect.

(3) change in the diameter of adipocytes around the ovary

In order to examine the effect of the composite composition consisting of Angelica extract and acid garlic extract of the present invention on obesity, the experimental results were measured by measuring the change in the diameter of the adipocyte around the ovary of the mouse to which the composite composition was administered. Indicated.

Table 6

As shown in Table 6, the mice fed the high fat diet used as the high fat diet (HFD) control group increased 225.05% in diameter of the adipocytes around the ovary compared to the mice fed the normal diet used as the control group. In the group administered simvastatin, silymarin, metformin, the group administered with Angelica extract or acid garlic extract alone, and the group administered with the composite composition of Angelica extract and acid garlic decreased 13.48-61.90%.

When the weight ratio of the composite composition of Angelica extract and acid garlic in the administration group is 1: 4- 6 and 2-4: 1, 54.95 diameters of adipocytes around the ovary were larger than the HFD control group and the Angelica extract or acid garlic extract alone. -61.90% reduction, of which the weight ratio of the composite composition was 60.37% and 61.90% in the 1: 4 and 4: 1 dose groups, respectively. The ovarian adipocyte diameter reduction effect was excellent, which was much better than the ovarian adipocyte administration (13.48%) and wild garlic alone administration (46.5).

Particularly, in the group where the mixing ratio of donkey and wild garlic was 4: 1, the anti-obesity effect was shown to be best suppressed by 60.90% of the increase in the diameter of ovarian adipocytes compared to the HFD control group.

(4) change in abdominal wall fat cell diameter

In order to determine the effect of the composite composition consisting of Angelica extract and acid garlic extract of the present invention on obesity, the experimental results of measuring the change in the abdominal wall fat cell diameter of the mice administered the composite composition are shown in Table 7 below. .

Table 7

As shown in Table 7, the change in the diameter of abdominal wall adipocytes was found to be increased to 242.70% in the high fat diet (HFD) control group, the control group, Angelica extract or wild garlic extract administered three control drugs. It was confirmed that the diameter of abdominal wall adipocytes was reduced to 22.58-59.94% in the group administered alone and 11 groups administered the Angelica and San garlic complex compositions.

When the weight ratio of the composite composition of Angelica extract and acid garlic in the administration group is 1: 2-6 and 2-4: 1, the effect of inhibiting the increase in the diameter of abdominal wall fat cells was 39.70-59.94% compared to the HFD control group. Among them, the weight ratio of the composite composition was 47.23% and 59.94%, respectively, in the weight ratio of 1: 4 and 4: 1, indicating that the abdominal wall adipocytes had an excellent diameter reducing effect (32.56%). ) And acid garlic alone (37.22%) showed better than abdominal wall fat cell diameter reduction effect.

In particular, in the case of the administration group of the mixed ratio of Angelica extract and acid garlic extract 4: 1, Compared with the HFD control group, abdominal wall fat cell diameter was reduced 59.94%, which was the best anti-obesity effect. Therefore, the composite composition of Angelica extract and acid garlic extract of the present invention reduces the weight gain compared to the group administered with Angelica extract or Mountain garlic extract alone as well as the high fat diet (HFD) control, and the fat weight around the ovary It is effective in reducing and increasing the diameter of peri-ovarian fat cells and abdominal wall fat cells, so that the pharmaceutical composition for the prevention or treatment of diabetes or diabetes complications, or the health function for the prevention or improvement of diabetes or diabetes complications It can be usefully used as a food.

Example 2 Effect of Complex Composition Composed of Angelica Extract and Acid Garlic Extract on Blood Glucose

Increasing blood sugar is the most basic symptom of diabetes (Sathishsekar D et al. Biol Pharm Bull., 2005, 28: 978-83), and high fat diet (HFD) fed mice are also used as a typical type 2 diabetes model. Surwit RS et al., Diabetes., 1988, 37: 1163-7; Yun SN et al., Arch Pharm Res., 2004, 27: 790-6). Therefore, in the present invention, a significant increase in blood glucose was caused by the feeding of high fat diet (HFD). In order to determine the effect of the composite composition consisting of Angelica extract and acid garlic extract of the present invention on the blood glucose, the experimental results of measuring the blood glucose change of the mice administered the composite composition prepared in Example 1 are shown in Table 8 below. Indicated.

Table 8

Feed Intake HFD Control Blood Sugar HFD Control

% relative to (g / mouse / dav)% relative to (me / dl) 6.54 ± 1.10 103.60 ± 11.84

HFD 4.67 ± 0.92 -28.59 249.80 ± 29.17 141.12

Reference drug Simvastatin 4.56 ± 0.93 -2.36 231.00 ± 31.43 -7.53

Psychological Mari 4.92 ± 0.75 5.35 199.00 ± 13.29 -20.34

Metformin 4.38 ± 0.61 -6.21 136.60 ± 11.87 -45.32 Alone Angelica 4.62 ± 0.61 -1.07 180.20 ± 14.22 -27.86 Group Garlic 4.88 ± 0.58 4.50 194.40 ± 8.02 -22.18

1: 1 4.68 ± 0.67 0.21 175.80 ± 34.74 -29.62

1: 2

Angelica Garlic 5.23 ± 0.83 11.99 186.00 ± 24.83 -25.54 Beam 1: 4 5.27 ± 0.82 12.85 147.40 ± 13.26 -40.99 ᄇ 1: 6 4.78 ± 0.78 2.36 157.60 ± 25.83 -36.91 Composition 1: 8 4.96 ± 0.70 6.21 196.80 ± 18.25 -21.22 administration group 1:10 4.58 ± 0.56 -1.93 186.80 ± 18.27 -25.22

2: 1 4.77 土 0.64 2.14 146.40 ± 15.73 -41; 39

(mg / mg)

4: 1 4.57 ± 0.90 -2.14 128.40 ± 21.62 -48.60

6: 1 5.06 ± 1.05 8.35 169.20 ± 30.87 -32.27

8: 1 5.20 ± 0.76 11.35 180.00 ± 30.85 -27.94

10: 1 4.79 ± 0.86 2.57 178.60 ± 14.10 -28.50 As shown in Table 8, mice fed high-fat diets used as high-fat diet (HFD) controls had lower blood sugar levels than those fed normal diets used as normal controls. 141.12% increased, except for the sivastatin-treated group, silymarin, metformin-treated group, donkey extract or wild garlic extract alone and 11 kinds of donkey extract and wild garlic The group receiving the complex composition was found to have a blood sugar reduction of 7.53-48.60% compared to the HFD control group.

When the weight ratio of the composite composition of Angelica extract and acid garlic in the administration group is 1: 4- 6 and 2-4: 1, it was confirmed that the blood sugar is reduced by 32.27—48.60% compared to the HFD control group, of which The weight ratio of the composite composition of 1: 4 and 4: 1 was 40.99% and 48.60%, respectively, and the effect on the hypoglycemic effect was excellent, which was when the donkey was administered alone (27.86%) and when the garlic was administered alone (22.18). Significantly better than the -Indicated.

Particularly, in the group where the mixing ratio of the Angelica extract and the garlic extract was 4: 1, the hypoglycemic effect was 48.60%. Therefore, the composite composition of the Angelica extract and acid garlic extract of the present invention is excellent in hypoglycemic effect as compared to the group administered with Angelica extract or Mountain garlic extract alone, as well as high-fat feed (HFO) control, diabetes mellitus or diabetes complications It can be usefully used as a preventive or therapeutic pharmaceutical composition for, or as a dietary supplement for the prevention or improvement of diabetes or diabetic complications.

Example 3 Effect of Complex Composition Composed of Angelica Extract and Mountain Garlic Extract on Hyperlipidemia

As hyperglycemia persists, hyperlipidemia occurs in the form of complications (Chen et al., 2005) and, in general, hyperglycemia has been a problem for reducing HDL with increasing LDL, triglycerides and total cholesterol (Milionis HJ et al. , Am Heart J., 2004, 148: 635-40; Forrester JS et al., Circulation., 2005, 111: 1847-54; Kamada T et al., Dig Liver Dis., 2005, 37: 39-43 ). Therefore, antihyperlipidemic effects on candidates are focused on increasing HDL content with decreasing blood LDL, triglyceride and total cholesterol content (Cheng JW Clin Ther., 2004, 26: 1368-87; Pirat). B et al., Anadolu Kardiyol Derg., 2004, 4: 318-22; Tan BK et al., Life Sci., 2005, 76: 2827-39).

(1) changes in blood cholesterol and triglyceride content

In order to determine the effect of the composite composition consisting of Angelica extract and acid garlic extract of the present invention on hyperlipidemia, the total cholesterol in blood to determine the abnormality of lipid metabolism of the mice administered the composite composition prepared in Example 1 Table 9 shows the change in the content of triglyceride and triglyceride content in blood.

Table 9 Gravity concentration One / dl)

Category Total Cholesterol HFD Control Triglycerides Compared to% compared to HFD Control ¾ Control Normal Group 99.00 ± 9.41 5 80 ± 17.17

HFD 219.40 ± 36.59 121.62 195.20 ± 21.31 284.25

Control drug simvasta 132.00 ± 11.02 -39.84 104.40 ± 22.20 -46.52

Psychomarin 149.20 ± 13.33 -32.00 132.60 ± 13.26 -32.07 Metformin 151.00 ± 18.03 -31.18 126.60 ± 13.99 -35.14 Alone Angelica 161.80 ± 19.12 -26.25 145.20 ± 11.69 -25.61 Administration Garlic 153.40 ± 12.95 -29.21 130.60 ± 10

1: 1 144.60 ± 8.47 -34.09 125.00 ± 17.39 -35.96 Angelica: Garlic Garlic 1: 2 141.40 ± 22.01 -35.55 123.00 ± 6.96 -36.99

1: 4 139.80 ± 12.93 -36.28 107.80 ± 8.76 -44.77 Compound 1: 6 144.80 ± 13.88 -34.00 118.20 ± 13.10 -39.40 Composition 1: 8 153.40 ± 16.62 -30.08 131.60 ± 18.09 -32.58 Dose 1:10 153.60 ± 20.77 -29.99 130.40 ± 25.50 -33.20

2: 1 141.10 ± 21.90 -35.68 120.40 ± 13.79 -38.32

(mg / mg)

4: 1 118.40 ± 15.18 -46.03 104.80 ± 15.35 -46.31

6: 1 145.40 ± 20.32 -33.73 120.60 ± 13.90 -28.22

8: 1 160.60 ± 17.94 -26.80 144.40 ± 20.32 -26.02

10: 1 152.80 ± 18.21 -30.36 145.60 ± 11.93 -25.41 As shown in Table 9, mice fed high-fat diets used as high-fat diet (HFD) controls were compared to mice fed normal diets used as normal controls. It was confirmed that the rester content was increased by 121.62% in the HFD control group compared to the normal control group, and the total cholesterol content in the blood was reduced by 26.25—46.03% in the HFD control group compared to the HFD control group.

Among the administration group, the administration group of the composite composition of Angelica extract and acid garlic weight of 1: 1-6 and 2-4: 1 is 34.00-46.03%, which is better than the HFD control group. Confirmed. Of these, 36.28% and 46.30%, respectively, in the weight ratio of 1: 4 and 4: 1 in the composite composition decreased blood total cholesterol content. It was shown that the total cholesterol in blood was better than the effect of reducing the content of Angelica alone (26.25%) and wild garlic alone (29.90%).

In particular, in the case of the administration group with the mixture ratio of Angelica extract and mountain garlic extract 4: 1, the anticholesterolemic effect was the most excellent with 46.03% of the total cholesterol reduction in blood. In addition, in the high-fat diet (HFD) control group, the blood triglyceride was increased to 284.25% compared to the normal control group, and the group Angelica extract or acid garlic extract administered simvastatin, silymarin, and metformin used as the control drug The serum triglyceride content was lowered in the 25.41-46.52% of all treatment groups, including the group administered alone and the group containing 11 kinds of Angelica extract and acid garlic complex.

When the weight ratio of the composite composition of Angelica extract and acid garlic in the administration group is 1: 4- 6 and 2-6: 1, it was confirmed that the triglyceride content in blood was reduced to 38.22-46.31% compared to the HFD control group. It became. Among them, the weight ratio of 1: 4 and 4: 1 in the composite composition was 44.77% and 46.31%, respectively.

Particularly, in the case of the administration group with the ratio of 4: 1 of Angelica extract and acid garlic extract, the triglyceride content of blood was 46.31%, showing the best antihyperlipidemic effect.

(2) changes in blood LDL and HDL

Low-density lipoprotein in blood to determine the abnormalities of lipid metabolism in mice to which the composite composition prepared in Example 1 was administered in order to examine the effect of the composite composition of Angelica extract and acid garlic extract of the present invention on hyperlipidemia ( LDL) and high density lipoprotein (HDL) were measured and shown in Table 10.

Table 10 ¾ concentration (mg / dl)

Category LDL HFD Control Group LR Control Group Normal Group 12.40 土 2.19 97.80 ± 8.41

HFD 26.40 ± 2.19 112.90 45.00 + 11.90 -53.99

Simvastarin 16.00 土 1.58 -39.39 58.40 ± 14.40 29.78 Control product silymarin 20.20 ± 3.70 -23.48 60.20 ± 5.63 33.78 Group Metformin 21.20 ± 3.27 -19.70 60.00 ± 3.54 33.33 Sole Angelica 20.80 ± 2.05 21.21 59.80 ± 3.96 32.89 Administration Group Garlic 20.40 ± 1.14 -22.73 60.40 ± 5.86 34.22

1: 1 19.00 ± 1.87 -28.03 64.20 ± 4.21 42.67 Angelica: Mountain garlic 1: 2 20.40 ± 1.67 -22.73 59.20 ± 2.49 31.56

1: 4 17.60 ± 1.67 -33.33 65.00 ± 8.80 44.44 Composite 1: 6 17.00 ± 1.58 -35.61 63.12 ± 4.12 40.26 Composition

1: 8 20.40 ± 1.67 -22.73 59.80 ± 3.27 32.89 Administration group 1:10 20.20 ± 3.11 -23.48 60.80 ± 2.68 35.11

(mg / mg) 2: 1 18.00 ± 2.24 -31.82 63.60 ± 4.34 41.33

4: 1 15.80 ± 1.92 -40.15 67.00 ± 4.85 48.89

6: 1 19.90 ± 1.41 -28.03 62.20 ± 8.04 38.22

8: 1 19.80 ± 1.92 -25.00 60.00 ± 6.44 33.33

10: 1 20.40 ± 1.44 -22.73 60.00 ± 1.87 33.33 As shown in Table 10, the blood low density lipoprotein (LDL) content is high-fat diet.

(HFD) the control group was found to increase to 112.90% compared to the normal control group, HFD in the control group, the group administered with Angelica extract or wild garlic extract alone, and the group administered the Angelica and acid garlic complex composition. It was confirmed that the blood LDL content is reduced to 19.70-40.15% than the control.

When the weight ratio of the composite composition of Angelica extract and acid garlic in the administration group is 1: 1-6 and 2-6: 1, the blood LDL content is increased to 28.03-40.15% compared to the HFD control group.

It was confirmed that there is an effect of suppressing, among which, in the administration group with the weight ratio of 1: 4 and 4: 1 of the composite composition, 33.33% and 40.15% showed the effect of reducing the low density lipoprotein content in blood, (21.21%) and acid garlic alone (22.73%) were superior to the low-density lipoprotein content of blood.

Particularly, in the case of the administration group with the ratio of 4: 1 of Angelica extract and acid garlic extract, the effect of reducing LDL content in blood was 40.15%, which showed the best antihyperlipidemic effect. In addition, the high-density lipoprotein (HDL) content in the blood was found to be 53.99% lower in the high-fat diet (HFD) control group than in the normal control group, except for the administration of simvastatin, which significantly increased the blood HDL content in comparison with the HFD control group. The rest of the administration group was confirmed to increase the blood HDL content of 29.78-48.89% compared to the HFD control group. Among the administration group, the administration group of the composite composition of Angelica extract and acid garlic was 1: 4-6 and 2-4: 1, and the HDL content was increased to 35.11-48.89% compared to the Angelica extract or acid garlic extract alone administration group. Among them, the weight ratio of 1: 4 and 4: 1 in the composite composition was 44.44% and 48.95%, respectively.

Particularly, in the case of the administration group with the ratio of 4: 1 of Angelica extract and wild garlic extract, the HDL content of the blood was increased by 48.89%, indicating that the antihyperlipidemic effect was the best. Therefore, the composite composition of the Angelica extract and acid garlic extract of the present invention is a total cholesterol content, blood triglyceride content and compared with the high-fat diet (HFD) control group, as well as the group administered Angelica extract or acid garlic extract alone It is excellent in reducing the low density lipoprotein content in blood and increasing the high density lipoprotein in blood, so it can be useful as a pharmaceutical composition for the prevention or treatment of diabetes or diabetes complications, or as a dietary supplement for the prevention or improvement of diabetes or diabetes complications. Can be.

Example 4 Effect of Complex Composition Composed of Angelica Extract and Garlic Extract

Feeding high fat feed is accompanied by hyperlipidemia and liver damage, and due to hypertrophy of liver cells caused by fatty stool, the increase of liver weight and the increase of blood AST and ALT content (Mukai M et al., Dig Dis Sci. 2002; 47: 549-55; Neves RH et al., Mem Inst Oswaldo Cruz. 2006; 101: 253-60). AST, commonly known as serum oxaltic transaminase (SG0T), and ALT, known as serum glutamic pyruvic transaminase (SGPT), are the most common hemochemical values for measuring liver damage (Sodikoff CH, A guide to laboratory diagnosis.2nd ed., Mosby: St. Louise, 1995: 1 36).

(1) change in liver weight

Changes in liver weight of mice to which the composite composition prepared in Example 1 was administered to investigate the effect of the natural product complex composition of Π species composed of Angelica extract and acid garlic extract are shown in Table 11 below. .

Table 11

Weight

Category Absolute Weight Relative Weight HFD Control

(e)% of%

Control Normal Group 1.368 ± 0.191 4.145 ± 0.138

HFD 1.698 ± 0.180 3.003 土 0.325 -27.55

(Compared to normal)

Reference drug simvastar 1.609 ± 0.232 3.319 ± 0.290 10.52

Dosing group

Psychomari 1.583 ± 0.324 3.242 ± 0.461 7.96

Metformin 1.528 ± 0.165 3.600 ± 0.433 19.88

Isolated Angelica 1.567 ± 0.146 3.356 ± 0.412 11.75

Administered acid garlic 1.435 ± 0.196 3.058 ± 0.216 1.83

1: 1 1.571 ± 0.240 3.235 ± 0.443 7.73 Angelica: Mountain garlic 1: 2 1.648 ± 0.148 3.266 ± 0.303 8.76

1: 4 1.651 ± 0.220 3.828 ± 0.503 27.47 Composite 1: 6 1.685 ± 0.340 3.675 ± 0.460 22.38

Composition 1: 8 1.457 ± 0.267 2.944 ± 0.606 -1.96

Administration group 1:10 1.467 ± 0.062 3.106 ± 0.375 3.43

2: 1 1.757 ± 0.352 3.465 ± 0.844 15.38

(mg / mg)

4: 1 1.560 ± 0.211 3.552 ± 0.303 18.28

6: 1 1.771 ± 116 3.049 ± 0.203 1.53

8: 1 1.733 ± 0.083 3.189 ± 0.098 6.19

10: 1 1.671 ± 0.156 3.313 ± 0.190 10.32 As shown in Table 11, a significant increase in absolute liver weight was recognized by high-fat feed, but a significant decrease in liver relative weight (27.55%) for more significant weight gain. Indicated. Groups receiving simvastatin and metformin used as reference drugs

， The administration of donkey alone and the composite composition with weight ratio of donkey and wild garlic were 1: 4-6 and 2-4: 1 in the group of 10.52-27.47% compared to the HFD control group. It was shown that the effect of increasing the amount, of which the weight ratio of the composite composition 1: 4 and 4: 1 in the administration group was 27.47% and 18.28%, respectively, the effect of increasing the liver relative weight was excellent.

In particular, in the case of the administration group of the combination ratio of Angelica extract and acid garlic extract 1: 4, the liver relative weight increase effect was 27.47%, it was confirmed that the liver protection effect is the most excellent.

(2) changes in blood AST and ALT

Effects of Complex Composition Containing Angelica Extracts and Mountain Garlic Extracts on Liver Damage In order to find out about the blood concentration of aspartame aminotransferase (AST) and alanine aminotransferase (ALT) the experimental results are shown in Table 12 below.

Table 12

As shown in Table 12, changes in blood concentrations of aspartame transcriptase (AST) and alanine aminotransferase (ALT), which are factors for detecting hepatocyte damage, were 145.58% higher in the HFD control group than in the normal control group, respectively. 49, 64% higher, HFD

It was confirmed that the AST concentration was reduced to 14.87-50.53% compared to the HFD control group, and the blood ALT concentration was reduced to 14.62-52.70% in all the administration groups except the control group simvastatin, which was similar to the control group. Confirmed.

Among the administration group, the administration group of the composite composition of Angelica extract and acid garlic was 1: 4-6 and 2: 1 4: 1, and the blood AST concentration was 43.05-50.53%, and the blood ALT concentration was 42.82-52.70%. It was confirmed that the AST and ALT contents in the blood were significantly reduced in comparison with the wild garlic extract alone administration group. Of these, 43.93% and 50.53% of AST concentrations were decreased in the group of the composite composition having a weight ratio of 1: 4 and 4: 1, respectively. ALT concentration reduction effects were 43.38% and 52.70%.

Particularly, in the group where the mixing ratio of Angelica extract and acid garlic extract was 4: 1, the effect of reducing the concentration of AST in blood was 50.53% and that of ALT was 52.70%, indicating the best liver protection. Therefore, the composite composition of the Angelica extract and acid garlic extract of the present invention is excellent in reducing the blood concentration of ALT and AST, which is an indicator of weight of liver and hepatocellular damage, thus preventing or treating diabetes or diabetic complications. It can be usefully used as a pharmaceutical composition or a dietary supplement for preventing or improving diabetes or diabetic complications.

Example 5 Effect of Complex Composition Composed of Angelica Extract and Garlic Extract on Kidney Damage

As the state of diabetes becomes chronic, kidney lesions are caused by glomerular atrophy and fibrosis, inflammatory cell infiltration, and tubular necrosis, and an increase in the content of urea nitrogen and creatinine in the blood, which is called diabetic nephropathy (Imaeda A). et al., Food Chem Toxicol. 200240: 1415-22; Trachtman H et al., Pediatr Nephrol. 200217: 20-9). The blood urea nitrogen (BUN) and creatinine (creatinine) content are the most representative blood chemistry of kidney status (Arch Med Res., 2004 Nov. Dec: 35 (6): 484-94). .

(1) changes in blood BUN and creatinine

Blood of the mouse to which the compound prepared in Example 1 was administered to investigate the effect of the composite composition consisting of Angelica extract and acid garlic extract Experimental results of measuring the concentration changes of heavy urea nitrogen (BUN) and blood creatinine are shown in Table 13 below.

Table 13

As shown in Table 13, mice fed the high fat diet used as a high fat diet (HFD) control group had an increase in blood urea nitrogen (BUN) content of 94.26% compared to mice fed the normal diet used as a normal control group. Except for the group that received simvastatin, a control that showed a blood BUN content similar to that of the HFD control group.

The BUN content in the blood decreased to 20.94-46.55% in the administration group.

The composite composition administration group in which the mixed weight ratio of Angelica extract and acid garlic extract in the administration group was 1: 4-6 and 2-4: 1, and the blood BUN content was lowered than the HFD control group by 35.96-46.55%. The effect of garlic alone was better than 30.33%. Among them, the weight ratio of 1: 4 and 4: 1 in the composite composition was 38.67% and 46.55%, respectively.

In particular, the composite composition administration group with the combined weight ratio of Angelica extract and wild garlic extract was 4: 1, showing 46.55% lower blood BUN content than the HFD control group. In addition, it was confirmed that the creatinine content in the HFD control group was increased by 154.29% compared to the normal control group, and the blood creatinine content was significantly different from the HFD control group in the HFD control group. It was confirmed that the creatinine content in the blood was reduced by 15.73-48.31%.

Among the administration group, the administration group of the composite composition of Angelica extract and wild garlic extract weighed 1: 4—6 and 2-4: 1 showed 35.96-48.31% to reduce blood creatinine content than the HFD control group. In the administration group with the weight ratio of the composition 1: 4 and 4: 1, the creatinine content was decreased by 35.96% and 48.31%, respectively. In particular, in the case of the administration group with the ratio of 4: 1 of Angelica extract and wild garlic extract, the creatinine content was reduced by 48.31% compared to the HFD control group, which showed the best renal protection effect. Therefore, the composite composition of the Angelica extract and acid garlic extract of the present invention is excellent in the effect of reducing blood urea nitrogen (BUN) content and blood creatinine content can be usefully used as a dietary supplement for diabetic or diabetic complications.

(2) change in the number of degenerative tubules

In order to examine the effect of the composite composition consisting of Angelica extract and acid garlic extract to determine the effect of kidney damage to the modified tubules of the mice administered with the compound prepared in Example 1 The results of the experiment in Table 14 Indicated.

Table 14

As shown in Table 14, the mice fed the high fat diet used as the high fat diet (HFD) control group showed an increase in the number of denatured tubules to 820.51% compared to the mice fed the normal feed used as the normal control group, and the HFD control group. The number of denatured tubules was reduced to 18.66-59.05% in the other groups except simvastatin, a control group that showed similar changes in the number of denatured tubules.

The combined weight ratio of Angelica extract and acid garlic extract in the administration group is 1: 1-6,

The composite composition group of 2-4: 1 was 33.70-59.05%, and the effect of reducing the number of tubules was better than that of the HFD control group, and the weight ratio of the composite composition of 1: 4 and 4: 1 group was higher. 42.34% and 59.05% showed better reduction of the number of denatured tubules, which was superior to that of Angelica alone (19.5) and acid garlic alone (27.86%).

In particular, the composite composition administration group with the combined weight ratio of Angelica extract and wild garlic extract was 4: 1, showing the best effect of reducing the number of denatured tubules (59.05¾) than the HFD control group. Therefore, the composite composition of the Angelica extract and acid garlic extract of the present invention reduces blood urea nitrogen (BUN) content and blood creatinine concentration, and has an excellent effect of reducing the number of denatured tubules for the prevention or treatment of diabetes or diabetic complications. It may be useful as a pharmaceutical composition or as a dietary supplement for the prevention or amelioration of diabetes or diabetic complications.

<Example 6> Effect of the composite composition composed of 4: 1 of the mixed weight ratio of Angelica extract and acid garlic extract on obesity

In order to determine the effect of the composite composition of the weight ratio of the Angelica extract and acid garlic extract having excellent effects on obesity, blood sugar, hyperlipidemia, liver damage and kidney damage in Examples 1 to 5 on obesity The following experiment was performed. Administration of Test Substance

The composite composition of the mixed weight ratio of the Angelica extract and acid garlic extract prepared in the same manner as in Example 1 was used by directly dissolving in distilled water, and fed a high fat feed to a total of 15 groups of 8 dogs each week from one week. Divided orally at 10 / kg once a day for 84 days. Three control drugs simvastatin, silymarin, and metformin were administered at 10, 100 and 250 mg / kg, respectively, and three types of Angelica, wild garlic and silver leaf extracts were administered at 100 mg / kg. A composite composition with a combined weight ratio of Angelica extract and Garlic extract of 4: 1 was administered at 200, 100 and 50 mg / kg. Table 15 shows the composition of the substance and the administration group.

Table 15

Effect of Mixed Weight Ratio of Angelica Extract and Garlic Extract on 4: 1 Composition

(1) effect on weight

Table 16 shows the weight change of mice to which the composite composition was administered in order to investigate the effect of the composite composition having a mixed weight ratio of 4: 1 and Angelica extract of the present invention on obesity.

Table 16

As shown in Table 16, the 84-day weight gain for the HFD control group showed a change of 190.54% compared to the normal control group. Simvastatin, silymarin, metformin and Angelica, wild garlic and Ginkgo biloba extract alone showed 33-6 weight loss compared to HFD control.

In the composite composition 200, 100 and 50 mg / kg of the composite weight ratio of Angelica extract and acid garlic extract, 4: 1, the weight loss effect was 41-55% compared to the HFD control group.

(2) Change of fat weight around the ovary

In order to investigate the effect of the composite composition of the Angelica extract and the garlic extract of the present invention in the mixed weight ratio of 4: 1 on the obesity, the experimental results were measured by measuring the change in the fat weight around the ovary of the mice to which the complex composition was administered. It is shown in Table 17 below.

Table 17

As shown in Table 17, the mice fed the high fat diet used as the high fat diet (HFD) control group showed a 1006.71% increase in the weight of the ovarian fat compared to the normal fed group. Simvastatin, silymarin, metformin and Angelica, wild garlic, and ginkgo biloba extract alone used as a control group showed a 15-76% decrease in fat weight around the ovary compared to the HFD control group.

In the composite composition 200, 100, and 50 mg / kg of the composite weight ratio of Angelica extract and acid garlic extract, 4: 1, the fat weight around the ovary was reduced to 50-76% compared to the HFD control group.

(3) change in the diameter of adipocytes around the ovary

Experimental results of measuring the change in the diameter of adipocytes around the ovary of the mice to which the composite composition was administered to investigate the effects of the composite composition of the Angelica extract and acid garlic extract of the present invention on the combined weight ratio of 4: 1 It is shown in Table 18 below.

Table 18 ^ Urn)

Category Ovary HFD Control

Fat cells (%)

Normal Control Normal Control 59.41 ± 5.84

HFD Control HFD 212.40 ± 31.18 257.52

(Compared to normal)

Simvastarin 170.53 ± 25.38 -19.71

Psychomarine 132.94 ± 13.55 -37.41

Metformin 112.96 ± 18.71 -46.82

Single dose group Angelica 165.66 ± 9.80 -22.01

Mountain scale 142.31 ± 28.42 -33.00

Milky Way ¾ 150.98 土 14.60 -28.92

Angelica: Mountain Garlic 200 me / kg 88.50 ± 14.60 -58.33

(4: 1) Composition 100 mg / kg 115.50 ± 18.30 -45.62

Administration group 50 mg / kg 139.03 ± 15.59 -34.54

As shown in Table 18, the mice fed the high fat diet used as the high fat diet (HFD) control group had a 257.52% increase in the diameter of the adipocytes around the ovary compared to the mice fed the normal diet used as the control group. Simvastatin, silymarin, metformin and Angelica, wild garlic and ginkgo biloba extract alone used as a 20-47% decrease in the diameter of the adipocytes around the ovary compared to the HFD control group.

In the composite composition 200, 100 and 50 mg / kg of the mixed weight ratio of Angelica extract and acid garlic extract, the diameter of peri-ovary fat cells was 35-58%, which was markedly reduced compared to the HFD control group.

(4) change in abdominal wall fat cell diameter

In order to examine the effects of the composite composition of the Angelica extract and the garlic extract of the present invention in a mixed weight ratio of 4: 1 on obesity, the experimental results were measured by measuring the change in the abdominal wall fat cell diameter of the mouse to which the complex composition was administered. Table 19 shows.

Table 19 ZJ- ᄇ Diameter (圆)

Bo HFD Control

Fat cell ()

Normal control group Normal group 68.96 ± 14 · 55

HFD control group HFD 20235 ± 13.68 193.41

(Compared to normal)

Simvastatin, the control group, 161.39 ± 32 · 38 -20.24

Psychology Mari 136 ・ 73 ± 30.21 -32.43

Metpo? 1 122.51 ± 9 ・ 52 -39.46

Single dose group Angelica 143.91 ± 23.96 -28.88

Mountain Garlic 139.14 ± 17.49 -31.24

Bank ¾ 153.67 ± 7.14 -24.05

Angelica: mountain garlic 200 me / ke 97.51 ± 20.60 -51.81

(4: 1) Composition 100 mg / kg 116.09 ± 21 · 25 -42.62

Administration group 50 mg / kg 133.29 ± 21 · 82 -34.13

As shown in Table 19, the mice fed the high fat diet used as the high fat diet (HFD) control group had a 193.41% increase in the diameter of abdominal wall fat cells compared to the mice fed the normal diet used as the control group. Simvastatin, silymarin, metformin and Angelica, wild garlic and ginkgo biloba extract alone administration group was found to decrease the diameter of abdominal wall fat cells by 20-39% compared to the HFD control group.

In the composite composition 200, 100 and 50 mg / kg of the composite weight ratio of Angelica extract and acid garlic extract, the diameter of abdominal wall adipocytes was 34-52%, compared with the HFD control group. Therefore, the results of the present experiment, the composite composition of the mixed weight ratio of Angelica extract and wild garlic extract 4: 1 significantly suppressed the weight gain, fat accumulation or fat cell hypertrophy of HFD fed mice in a dose-dependent manner, Angelica extract and acid The anti-obesity effect of the composite composition with a combined weight ratio of garlic extract of 4: 1 was confirmed.

Example 7 Effect of Complex Composition Composed of 4: 1 of Angelica Extract and Mountain Garlic Extract on Blood Glucose

In order to examine the effect of the composite composition of the Angelica extract and acid garlic extract of the present invention in a mixed weight ratio of 4: 1 on blood glucose, an experiment was performed by measuring the change in blood glucose of the mouse administered with the composite composition prepared in Example 6 The results are shown in Table 20 below. Table 20

As shown in Table 20, the mice fed the high fat diet used as the high fat diet (HFD) control group showed a 131.67% increase in blood glucose level compared to the mice fed the normal diet used as the normal control group. Except for simvastatin, silymarin, metformin and Angelica, wild garlic and ginkgo biloba extract alone administration group was confirmed that the blood glucose is reduced by 21-40% compared to the HFD control group.

In the composite composition 200, 100 and 50 mg / kg of the composite weight ratio of the Angelica extract and the garlic extract of 4: 1, the blood glucose was significantly reduced to 30-49% compared to the HFD control group.

<Example 8> Effect of the composite composition of 4: 1 weight ratio of Angelica extract and acid garlic extract on hyperlipidemia

(1) changes in blood cholesterol and triglyceride content

In order to examine the effects of the composite composition of the Angelica extract and acid garlic extract of the present invention in a mixed weight ratio of 4: 1 on hyperlipidemia, the lipid metabolism of mice administered with the composite composition prepared in Example 6 was examined. The changes in total cholesterol in blood and triglyceride content in blood are shown in Table 21 below. Table 21

As shown in Table 21, the mice fed the high fat diet used as the high fat diet (HFD) control group showed a 129.05% increase in the total cholesterol content compared to the mice fed the normal diet used as the normal control group. Simvastatin, silymarin, metformin, and Angelica, wild garlic and ginkgo biloba extract alone used as a total cholesterol was reduced by 22-39% compared to the HFD control group.

In the composite composition 200, 100 and 50 mg / kg of the mixed weight ratio of Angelica extract and acid garlic extract, 4: 1, the total cholesterol content was 31-47% compared to the HFD control group. In addition, in the high-fat diet (HFD) control group, the blood triglyceride was increased to 297.76% compared to the normal control group, and the simvastatin, silymarin, metformin and donkey, wild garlic, and ginkgo biloba extract alone were used as control. Compared with the HFD control group, the blood triglyceride was confirmed to be reduced by 23-35%.

In the composite composition 200, 100 and 50 mg / kg of the mixed weight ratio of Angelica extract and acid garlic extract, the concentration of triglyceride in blood was 30-49% compared to the HFD control group. (2) changes in blood LDL and HDL

In order to examine the effects of the composite composition of the Angelica extract and acid garlic extract of the present invention in a mixed weight ratio of 4: 1 on hyperlipidemia, the lipid metabolism of mice administered with the composite composition prepared in Example 6 was examined. The low density lipoprotein (LDL) and high density lipoprotein (HDL) in blood were measured and shown in Table 22.

Table 22

As shown in Table 22, mice fed the high fat diet used as a high fat diet (HFD) control group had a 123.66% increase in low-density lipoprotein (LDL) content in the blood compared to mice fed the normal diet used as a normal control group. Simvastatin, silymarin, metformin and Angelica, wild garlic and ginkgo biloba extract alone used as a control drug showed a 22-34% decrease in LDL content compared to the HFD control group.

In the composite composition 200 100 and 50 mg / kg of the combined weight ratio of Angelica extract and acid garlic extract, the low density lipoprotein (LDL) content was 30-47%. In addition, the high-density lipoprotein (HDL) content in blood was found to be reduced by 60.13% in the high-fat diet (HFD) control group compared to the normal control group. Simvastatin, silymarin, metformin and Angelica, wild garlic and ginkgo biloba extracts were used as control drugs. It was confirmed that the high density lipoprotein (HDL) content in the blood increased by 2% by 33% compared to the HFD control group.

In the composite composition 200 100 and 50 mg / kg of the mixed weight ratio of Angelica extract and acid garlic extract, the concentration of HDL in the blood was 39-52%, compared with the HFD control group.

Example 9 The Effect of Complex Composition Composed of 4: 1 of Angelica Extract and Acid Garlic Extract on Liver Damage

(1) change in liver weight

Changes in liver weight of mice to which the composite composition prepared in Example 6 was administered to investigate the effect of the composite composition having a weight ratio of 4: 1 of the Angelica extract and acid garlic extract according to the present invention on liver damage Is shown in Table 23 below.

Table 23

As shown in Table 23, the remarkable absolute liver An increase was recognized, but liver weight showed a significant decrease (25.96%) as the weight gain was more significant. Simvastatin, silymarin, metformin and Angelica, wild garlic and ginkgo biloba extract alone used as a control group was found to increase the relative weight of the liver by 7-19% compared to the HFD control group.

In the composite composition 200, 100 and 50 mg / kg of the composite weight ratio of Angelica extract and acid garlic extract, 4: 1, the relative weight to liver weight was 14-35% compared to the HFD control group.

(2) changes in blood AST and ALT

Blood concentrations of aspartame aminotransferase (AST) and alanine aminotransferase (ALT) in order to investigate the effects of a composite composition with a weight ratio of 4: 1 of the Angelica extract and acid garlic extract according to the present invention on liver damage The experimental results are shown in Table 24 below.

Table 24

As shown in Table 24, the change in blood plasma concentrations of aspartame transcriptase (AST) and alanine aminotransferase (ALT), which are factors for detecting hepatocyte damage, was 143.63% in the high-fat diet (HFD) control group compared to the normal control group, respectively. 543.39% was high, The silymarin, metformin and Angelica, wild garlic and ginkgo biloba extract alone, except for the control group simvastatin, which were similar to the HFD control group, showed AST and ALT levels of 29-43% and 29-, respectively, compared to the HFD control group. A 44% decrease was confirmed. In the composite composition 200, 100 and 50 mg / kg of the mixed weight ratio of Angelica extract and acid garlic extract, the AST and ALT concentrations were reduced to 36-46% and 37-46%, respectively, compared to the HFD control group. Indicated.

<Example 10> Effect of the composite composition consisting of 4: 1 weight ratio of Angelica extract and acid garlic extract effect on kidney damage

(1) changes in blood BUN and creatinine

Blood urea nitrogen (BUN) of mice to which the compound prepared in Example 6 was administered to investigate the effect of the composite composition having a mixed weight ratio of 4: 1 of the Angelica extract and acid garlic extract according to the present invention on kidney damage ) And the experimental results of measuring the change in concentration of creatinine in the blood are shown in Table 25 below.

Table 25

As shown in Table 25, mice fed the high fat diet used as the high fat diet (HFD) control group were fed the mice fed the normal feed used as the normal control group. Blood urea nitrogen (BUN) content was increased to 127.62%, and silymarin, metformin and donkey, acid garlic and ginkgo biloba were excluded, except for the control group simvastatin, which showed a blood BUN content similar to the HFD control group. It was confirmed that the urea nitrogen (BUN) content in the blood alone was 27-36% lower than the HFD control group.

In the composite composition 200, 100 and 50 mg / kg of the composite weight ratio of Angelica extract and acid garlic extract, 4: 1, the blood urea nitrogen (BUN) content was 33-46%. In addition, the blood creatinine content of the HFD control group was found to increase by 157.89% compared to the normal control group. Acid garlic and ginkgo biloba extract alone administration group showed a 28-36% decrease in blood creatinine content compared to the HFD control group.

In the composite composition 200, 100 and 50 mg / kg of the composite weight ratio of Angelica extract and acid garlic extract, 4: 1, the blood creatinine content was 33-46%, which was remarkably reduced compared to the HFD control group.

(2) change in the number of degenerative tubules

Changes in the number of denatured tubules of mice to which the compound prepared in Example 6 was administered to investigate the effect of the composite composition having a mixed weight ratio of 4: 1 and Angelica extract of the present invention on kidney damage The experimental results are shown in Table 26 below.

Table 26

Classification Organization Type

Denatured tubule number compared to HFD control

C / 100 Taxiology) (%)

Normal Control Normal Control 7.25 ± 4.10

HFD Control HFD 72.13 + 11.12 894.83

(Compared to normal)

Simvastatin 71.00 ± 13.56 -1.56

Psychology Mari 41.63 ± 14.85 -42.29

Metpo? 1 48.00 土 4.69 -33.45

Single dose group Angelica 54.38 ± 8.48 -24.61

Mountain Mart 54. ⁶³ ± 8.73 -24.26

Ginkgo biloba 52.38 ± 12.03 -27.38

Angelica: Mountain Garlic 200 me / ke 23.00 ± 9.97 -68.11

(4: 1) Combination Composition 100 mg / kg 38.88 ± 12.21 -46.10 Administration Group 50 mg / kg 44.75 ± 7.85 -37.95

As shown in Table 26, the mice fed the high fat diet used as the high fat diet (HFD) control group showed an increase in the number of denatured tubules to 894.38% compared to the mice fed the normal diet used as the normal control group, and the HFD control group. In the group treated with silymarin, metformin and Angelica, wild garlic and ginkgo biloba extract alone, except for the control group simvastatin, which showed a similar number of denatured tubules, the number of denatured tubules was reduced by 24-42% compared to the HFD control group.

In the composite composition 200, 100 and 50 mg / kg of the composite weight ratio of Angelica extract and acid garlic extract, the number of denatured tubules was 38-68%, which was markedly reduced compared to the HFD control group. Therefore, the composite composition of the Angelica extract and acid garlic extract according to the present invention has a combined weight ratio of 4: 1, which shows excellent anti-obesity, anti-hyperlipidemia, hypoglycemic effect, hepatoprotective effect and kidney protection effect depending on the dose. It can be usefully used as a composition for the prevention, treatment and improvement of complications.

Example 11 Effect of a Complex Composition of 4: 1 of Angelica Extract and Acid Garlic Extract on the Diabetes of Streptozotocin (STZ) -Induced Diabetes Animal Model Streptozotocin (STZ) is a selective pancreatic islet Destroys insulin-producing B cells in the body, leading to diabetes (Hsu and Crump, Philadelphia, 1989, 186-201). It is known to cause atrophy and decrease of water due to inflammation reaction of pancreatic islet.

(Bonnevie—Nielsen et al .. Diabetes. 1981, 30, 424-9; Higdon et al., Vet Pathol. 2001, 38, 715-20), based on morphological changes in pancreatic islets and changes in insulin and glucagon producing cells (Kobayashi et al., Phyt other Res. 2002, 16, 377-82; Kavalali et al., J Ethnopharmacol. 2003, 84, 241-5; Kim et al., Biol Pharm) Bull. 2006, 29, 477-82; Kim et al., Biosci Biotechnol Biochem. 2007, 71, 1527-34). Preparation of Streptozotocin (STZ) -Induced Diabetes Animal Model

In the present invention, the pharmacological effects of diabetes mellitus and diabetic complications according to the administration dose of the composite composition of the Angelica extract and the garlic extract of 4: 1 were evaluated using stramtozotocin (STZ) -induced diabetic rats. STZ was dissolved in 50 mM complete citrate solution (pH 6.0) to induce diabetes by single intraperitoneal administration at a dose of 60 mg / kg / 5 n ^. In normal media controls, the same route of citrate complete citrate solution was used instead of STZ. Was administered. Administration of Test Substance

Divided into 6 groups of 8 animals in each group, the composite composition consisting of the weight ratio of Angelica extract and wild garlic extract was 4: 1, and dissolved in sterile distilled water at the capacity of 200, 100 and 50 mg / kg, respectively. 22 days after the administration of STZ at a concentration of 28 days orally administered, silymarin was also dissolved in sterile distilled water at a dose of 100 mg / kg was administered at 5 mt / kg. Meanwhile, sterile distilled water was administered at 5 mi / kg in the normal medium control group and the STZ control group, respectively. Table 27 shows the composition of the substances and the administration group.

Table 27

STZ 50 tns / ks Angelica: Acid garlic (4: 1) 50 ms / distilled water 5 mi A composite composition consisting of 4: 1 weight ratio of Angelica Extract and Mountain Garlic extract of Streptozotocin (STZ) -induced diabetic animal model. Impact on Diabetes

(1) Effect on blood sugar

Table 28 shows the changes in blood glucose of rats to which the composite composition was administered in order to examine the effects of the composite composition having a mixed weight ratio of 4: 1 of the Angelica extract and acid garlic extract of the present invention on STZ-induced diabetes.

Table 28

As shown in Table 28, the rats used as the STZ control group had an increase in blood sugar level of 5974.14% compared with the rats used as the normal control group, and the blood glucose reduction group of the silymarin group used as the control drug was 62.79% lower than that of the STZ control group. Indicated. In the composite composition 200, 100 and 50 mg / kg of the mixed weight ratio of Angelica extract and acid garlic extract, the blood sugar level was significantly reduced by 49-80% compared to the STZ control group and was significantly higher than the STZ control group. Reduction of blood glucose is dose dependent in all dose groups. For example, the composite composition with the combined weight ratio of Angelica extract and acid garlic extract was found to have a relatively good hypoglycemic effect.

(2) Effect on histopathological changes of pancreas

Histopathological changes in the pancreas of rats to which the composite composition was administered in order to investigate the effect of the composite composition having a combined weight ratio of 4: 1 of the Angelica extract and acid garlic extract according to the present invention on STZ-induced diabetes Is shown in Table 29.

Table 29

As shown in Table 29, the rats used as the STZ control group had a 69% decrease in the number of pancreatic islets compared to the rats used as the normal control group, and the number of 112% of the pancreatic islets in the silymarin-administered group used as the reference drug compared to the STZ control group. An increase was shown. Pancreatic islets showed a significant increase in the number of pancreatic islets in the combined composition of 200, 100 and 50 mg / kg of pancreatic extract and wild garlic extract in a ratio of 4: 1 compared to the STZ control group.

In addition, the rats used as the STZ control group showed a decrease of 77% in diameter of the pancreatic islets compared to the rats used as the normal control group, and the silymarin-administered group used as the control drug showed a 152% increase in the diameter of the pancreatic islets compared to the STZ control group. In the composition of 200, 100 and 50 mg / kg of the composite composition with the combined weight ratio of Angelica extract and acid garlic extract, 4: 1 In contrast, the diameter of the pancreatic islets was 121-208%, indicating a significant increase.

(2) Effect on the number of immune response cells in pancreatic islet

Changes in the number of immune-responsive cells in the pancreatic islet of the rats to which the complex composition was administered were examined in order to examine the effects of the combined weight ratio of the Angelica extract and the garlic extract according to the present invention on the STZ-induced diabetes of 4: 1. Table 30 shows.

Table 30

As shown in Table 30, the rats used as the STZ control group had an 82% reduction in the number of insulin immunosuppressive cells in the pancreatic islets compared to the rats used as the normal control group, and 102% compared to the STZ control group in the silymarin-administered group used as the control drug. Insulin immunoreaction cells in the pancreatic islet increased. In the composite composition 200, 100 and 50 mg / kg of the mixed weight ratio of Angelica extract and wild garlic extract, the number of insulin immune cells in the pancreatic islet was 71-212%, compared with the STZ control group. It was. In addition, as shown in Table 30, the rats used as the STZ control group had a 135% increase in the number of glucagon immune reaction cells in the pancreatic islet compared to the rats used as the normal control group, and the STZ control group in the silymarin-administered group used as the reference drug. The number of glucagon-immunoreactive cells in pancreatic islet was decreased by 46%. In the composite composition 200, 100 and 50 mg / kg of the mixed weight ratio of Angelica extract and acid garlic extract, the number of glucagon immune reaction cells in the pancreatic islet was 27-48%. . As indicated above, a decrease in the mean diameter with a decrease in the number of pancreatic islets, namely atrophy, was recognized in the STZ control group, and an increase in glucagon immune response cells was observed with a decrease in the number of insulin immunosuppressive cells in the pancreatic islets. The administration of three doses of Angelica extract and acid garlic extract composites significantly suppressed the morphological changes of the pancreas and changes in insulin and glucagon immune response cells.

Therefore, the composite composition of Angelica extract and acid garlic extract is expected to exhibit antidiabetic activity as a protective action against pancreatic B cells directly, and the composite composition of the mixed weight ratio of Angelica extract and acid garlic extract of the present invention is 4: 1. It has been shown to have an antidiabetic effect similar to that of silymarin, which is known to be effective in doses of diabetes.

<Example 12> Effect of the composite composition of the weight ratio of Angelica extract and acid garlic extract of 4: 1 on the kidney of streptozotocin (STZ) -induced diabetic animal model

(1) change in height weight

Changes in the kidney weight of rats induced with diabetes in order to investigate the effects of the composite composition of the Angelica extract and acid garlic extract according to the present invention in a mixed weight ratio of 4: 1 on kidney damage caused by STZ-induced diabetes Experimental results are shown in Table 31 below.

Table 31

As shown in Table 31, rats used as the STZ control group were the normal control group. Absolute and relative weights were increased by 96% and 275%, respectively, compared to the rats used, and silymarin-treated groups used as reference drugs showed 17 and 30% reductions in absolute weight and relative weight, respectively, compared to the STZ control group. In the composite composition 200, 100 and 50 mg / kg of the mixed weight ratio of Angelica extract and acid garlic extract, the absolute weight and the relative weight were 23-26% and 28-38%, respectively, compared to the STZ control group. Indicated.

(2) change in blood BUN

Blood Urea Nitrogen (BUN) of rats induced diabetes mellitus in order to investigate the effect of the composite composition of 4: 1 weight ratio of Angelica extract and acid garlic extract according to the present invention on kidney damage caused by STZ-induced diabetes Experimental results of measuring the change in concentration are shown in Table 32 below.

Table 32

As shown in Table 32, rats used as the STZ control group had an 8600% increase in blood urea nitrogen (BUN) content compared to the rats used as the normal control group, and 67% of the silymarin-administered group used as the control group compared to the STZ control group. It showed a decrease in blood urea nitrogen (BUN) content. In the combination composition 200, 100 and 50 mg / kg of the mixed weight ratio of Angelica extract and acid garlic extract, the concentration of urea nitrogen (BUN) was 43-87% compared to the STZ control group.

(3) changes in the content of blood creatinine Blood creatinine content in rats induced with diabetes in order to investigate the effects of a composite composition of 4: 1 of the Angelica extract and acid garlic extract according to the present invention on kidney damage caused by STZ-induced diabetes The change is measured and the experimental results are shown in Table 33 below.

Table 33

As shown in Table 33, the rats used as the STZ control group had a 1140% increase in blood creatinine content compared to the rats used as the normal control group, and in the silymarin-administered group used as the reference drug, 56% of the blood cleavage was compared to the STZ control group. It showed a decrease in the atinine content. In the composite composition 200, 100 and 50 mg / kg of the mixed weight ratio of Angelica extract and acid garlic extract, the concentration of creatinine in the blood was 44-85%.

(4) histopathological changes of kidney

In order to examine the effects of the composite composition of the Angelica extract and the garlic extract of the present invention in combination weight ratio of 4: 1 on the kidney damage caused by STZ-induced diabetes, The histopathological changes of the kidney, such as the number of tubules, are shown in Table 34 below.

Table 34 Classification Histopathological Change

Degenerated glomeruli STZ control Denatured tubules STZ control τ Contrast (%) 丁 Contrast (%)

(/ 100 (/ 100

Glomeruli) tubules)

Normal Control Normal 2.50 ± 1.69 6.88 ± 4.42

STZ Control STZ 71.50 ± 7.89 2760.00 63.63 ± 15.17 825.45

(Compared to the normal group) compared to the control group water control group Psychomari 22.88 ± 6.22 -68.01 28.13 ± 9.45 -55.80 Angelica: Mountain garlic (4: 200 ms / ke 11.25 ± 2.38 -84.27 17.88 ± 6.94 -71.91

100

1) Complex composition mg / kg 23.50 ± 8.93 -67.13 31.38 ± 7.42 -50.69 Administration group 50 mg / kg 36.25 ± 14.79 -49.30 39.25 ± 6.94 -38.31 As shown in Table 34, rats used as STZ controls were used as normal controls. The number of denatured tubules was increased by 2760% compared with rats, and the silymarin-treated group used as a control drug showed a 68% decrease in the number of denatured tubules compared to the STZ control group. In the composite composition 200, 100 and 50 mg / kg of the mixed weight ratio of Angelica extract and acid garlic extract, the number of denatured tubules was 49-84%.

In addition, as shown in Table 34, the rats used as the STZ control group had a 825% increase in the number of degenerative glomeruli compared to the rats used as the normal control group, and 56% of the denatured glomeruli in the silymarin-administered group used as the reference drug compared to the STZ control group. A decrease in number was shown. In the composite composition 200, 100 and 50 mg / kg of the composite weight ratio of Angelica extract and acid garlic extract, the number of denatured glomeruli was 38-72%. As indicated above, 21 days after STZ administration, all STZ-administered groups showed a significant increase in blood BUN and creatinine content, and it was judged that diabetic nephropathy by STZ administration was relatively well-induced before initiation of the candidate substance. Since the weight, increase in blood BUN and creatinine content, capillary dilatation glomerular atrophy and increase in degeneration tubules were significantly inhibited by administration of all doses of Angelica extract and Garlic extract complex compositions, Angelica Extract and Garlic Extract complex compositions It is believed to be a very effective suppressor of sexual nephropathy and is comparable to silymarin at the same dose It was confirmed that there is an effect on diabetic nephropathy.

Example 13 The Effects of Complex Compositions of Mixed Weight of Angelica Extract and Mountain Garlic Extract on 4: 1 on Immune Activity of Straptozotocin (STZ) —Induced Diabetes Animal Model

Significant immunosuppression occurs in diabetes mellitus, which causes secondary infections to occur easily and is considered as one of the important diabetic complications in immunosuppression. In diabetes, significant atrophy of lymphatic machines such as breast and spleen, resulting in weight loss and cytokines changes in cytokine (Tabata et al., Cell Immunol. 1984, 89, 250-8; Clary et al., Immunopharmaco 1 ogy-1990, 20, 153-64; Mic et al., Comp Med. 2007, 57, 476-81; Briede et al., Cell Biochem Funct. 2008, 26, 908-15; Rubinstein et al., Clin Exp I'unol. 2008, 154,235-46). Therefore, in the present invention, the effects of the Angelica extract and acid garlic extract complex composition on the immune activity were measured by measuring changes in the thymus and spleen of the STZ-induced diabetic animal model.

(1) change in thymus weight

To determine the effect of the composite composition of the Angelica extract and wild garlic extract according to the present invention on the immune activity of the STZ-induced diabetic animal model, the composite weight ratio of 4: 1 was determined. The change is measured and the results are shown in Table 35 below.

Table 35

As shown in Table 35, the rats used as the STZ control group had 90 and 80% reductions in the absolute and relative weights of the thymus gland compared to the rats used as the normal control group, respectively. Thyroid gland weight and bed mass increased by 217% and 166%, respectively. In the composite composition with mixed weight ratio of Angelica extract and Mountain garlic extract, 4: 1, 200, 100 and 50 mg / kg, the absolute and relative weights of the thymus gland were 214-316% and 213-243%, respectively, compared to the STZ control group. It showed an increase effect.

(2) change in spleen weight

To investigate the effect of the composite composition of the Angelica extract and wild garlic extract according to the present invention on the immune activity of the STZ-induced diabetic animal model, the composite weight ratio of 4: 1 was used. The change is measured and the experimental results are shown in Table 36 below.

Table 36

As shown in Table 36, the rats used as the STZ control group had 58 and 18% reductions in the absolute and relative weights of the spleen compared to the rats used as the normal control group, respectively. The absolute weight and phase mass of the spleen increased by 58% and 34%, respectively. In the composite composition 200, 100 and 50 mg / kg of the common weight ratio of the Angelica extract and the garlic extract, the absolute and relative weights of the spleen were 35-75% and 29-46%, respectively, compared to the STZ control group. It showed a marked increase effect.

(3) Histopathological changes of thymus

Tissues of the mammary gland of rats induced with diabetes in order to investigate the effect of the composite composition of the mixed weight ratio of Angelica extract and wild garlic extract according to the present invention on the immune activity of STZ-induced diabetic animal model The experimental results of the pathological changes are shown in Table 37 below.

Table 37

As shown in Table 37, the rats used as the STZ control group had a 56% reduction in the total thickness of the thymus lobules compared with the rats used as the normal control group, and the total thickness of the thymus lobules was 30 compared to the STZ control group in the silymarin-administered group used as the reference drug. A percentage increase was shown. In the composite composition 200, 100 and 50 mg / kg of the mixed weight ratio of Angelica extract and acid garlic extract, the total thickness of the thoracic lobule was 21-49¾>, respectively, compared to the STZ control group.

In addition, as shown in Table 37, the rat used as the STZ control group had a 62% decrease in the thickness of the thyroid cortex compared with the rat used as the normal control group, and in the silymarin-administered group used as the reference drug, the thyroid cortex thickness was lower than that of the STZ control group. 증가 2 increase was shown. In the composite composition 200, 100 and 50 mg / kg of the mixed weight ratio of Angelica extract and acid garlic extract, the thyroid cortex thickness was 59-108%, respectively, compared with the STZ control group, which showed a significant increase effect.

(4) Histopathological changes in the spleen

In order to examine the effects of the composite composition of the Angelica extract and the garlic extract of the present invention, the combined weight ratio of 4: 1 on the immune activity of STZ-induced diabetic animal model, the spleen tissue of the rat induced diabetes The experimental results of the pathological changes are shown in Table 38 below. Table 38

As shown in Table 38, the rats used as the STZ control group had a 46% reduction in the total spleen thickness compared to the rats used as the normal control group, and the total spleen thickness was 30 compared to the STZ control group in the silymarin treated group used as the control. A% increase was shown. In the composite composition 200, 100 and 50 mg / kg of the composition weight ratio of Angelica extract and acid garlic extract of 4: 1, the total spleen thickness was 21-49%, which was remarkably increased compared to the STZ control group.

In addition, as shown in Table 38, the rats used as the STZ control group had a 60% decrease in the mean diameter of the splenic white medulla compared to the rats used as the normal control group, and the silymarin-administered group used as the reference drug compared to the STZ control group. The average diameter of the white water was reduced by 56%. In the composite composition 200, 100 and 50 mg / kg of the mixed weight ratio of Angelica extract and acid garlic extract, 4: 1, the mean diameter of splenic white medulla was 44-117%, respectively, compared to the STZ control group. As indicated above, in the STZ control group, histopathological atrophy was recognized with significant reduction of thymus and spleen weight, but changes in thymus and spleen by administration of all three Angelica extracts and acid garlic extracts Dependently inhibited, Angelica extract and wild garlic extract complex composition are considered to effectively inhibit the immune immune suppression associated with diabetes mellitus, and the same dose of silymarin And similar immunological effects.

Example 14 Young Hing Effect of Combination Composition of Angelica Extract and Mountain Garlic Extract in Combination Weight Ratio 4: 1 on Eye Protection of Streptozotocin (STZ) -Induced Diabetes Animal Model:

Cataract and retinal injury are also one of the most common complications of diabetes. About 2。 of diabetic patients suffer from diabetic cataract, and eye damage caused by diabetes can be caused by various complex mechanisms. (Jarrett and Keen, Lancet. 1976, 2, 1009-12; Klein et al., Ophthalmology. 1985, 92, 1191-6; Jahn et al., Ophthalmic Res. 1986, 18, 112) 6; Brown and Bron, But t erwot h-He i nemann. 1996, 19 211; Swamy-Mruthint i et al., Curr Eye Res. 1999, 18, 423-9), oxidative ive stress Also known as one of the pathogenic mechanisms (Boscia et al., Invest Ophthalmol Vis Sci. 2000, 41, 2461-5; Spec tor, J Ocul Pharmacol Ther. 2000, 16, 193-201; Ozmen et al., Clin Biochem. 2002, 35, 69-72; Ramana et al., J Diabetes Complications. 2004, 18, 177-82). Cataract levels and histopathological changes of eyeballs have been used as a criterion for evaluating the effects of candidates on diabetic eye damage. In addition, there is a significant increase in cataracts in diabetic eye damage, and lens damage, retinal atrophy and angiogenesis are increased. (Barber et al., J Clin Invest. 1998, 102, 783-91; Yoshida et al., Biol Pharm Bull. 2004, 27, 338—44; ametaka et al., J Pharmacol Sci. 2008a, 106, 144-51; Kametaka et al., J Pharmacol Sci. 2008b, 106, 651-8; Saito et al., Biol Pharm Bull. 2008, 31, 1959-63). Therefore, in the present invention, by measuring the cataract levels and histopathological changes of eyeballs in the animal model of STZ-induced diabetes, the effects of the complex composition of Angelica extract and acid garlic extract on eye protection were as follows.

(1) changes in cataract levels

In order to investigate the effect of the composite composition consisting of Angelica extract and acid garlic extract on the eye protection of the STZ-induced diabetic animal model, the change of cataract levels in the rats induced with diabetes was measured and the results are shown in Table 39. It was.

Table 39 Category Baek ^^-Figure

Visual Value STZ Control Quantification Compared to STZ Control (%) Image-Analytical Contrast

shame (%)

Normal Control Normal Control 0.38 ± 0.52 9.29 ± 2.88

STZ control STZ 4.38 ± 0.74 1066.67 50.36 + 6.04 441.99

(Compared to the normal group (compared to the normal group)) Psychomaridae control group 2.63 ± 0.92 -40.00 31.77 ± 8.78 -36.91 Angelica: Mountain garlic (4: 200 me / ks 2.13 ± 0.64 -51.43 25.91 ± 6.98 -48.55 1) Complex composition 100 mg / kg 2 · 75 ± 0 · 89 −37.14 32.23 ± 7.50 −36.00 administration group 50 mg / kg 3.00 ± 1 · 07 −31.43 34.72 ± 10.93 −31.06 As shown in Table 39, rats used as STZ controls were normal. The cataract visual acuity was increased by 1067% compared to rats used as a control group, and the cataract visual acuity was decreased by 40¾> compared to the STZ control group in the simarin group administered as a control. In the composite composition 20 with the combined weight ratio of Angelica extract and acid garlic extract, 100- and 50 mg / kg-administered group showed a 31-51% significant reduction in cataract visual acuity compared to the STZ control group.

In addition, as shown in Table 39, the rats used as the STZ control group had a 442% increase in cataract quantitative image value compared to the rats used as the normal control group, and the quantitative image of cataracts compared to the STZ control group in the silymarin-administered group used as the reference drug. The figure showed a 37% decrease. In the 200, 100 and 50 mg / kg of the composite composition with the mixed weight ratio of Angelica extract and acid garlic extract, the cataract quantitative image value was 31-49% markedly reduced compared to the STZ control group.

(2) Histopathological changes of lens

Tissue of the lens of rats induced diabetes mellitus in order to investigate the effect of the composite composition of 4: 1 of the Angelica extract and acid garlic extract according to the present invention on the eye protection of STZ-induced diabetic animal model The experimental results of the pathological changes are shown in Table 40 below.

Table 40 Histopathological changes of the lens

Damage level STZ control Damaged area (%) Thick ("m / lens) compared to STZ control (%) Normal control Normal 0.25 + 0.46 432.95 ± 107.56

STZ Control STZ 2.25 ± 0/711 800.00 1744.33 ± 326.77 302.90

(Normal vs. (Normal vs. Non)) Psychiatric Contraceptive Groups 1.38 ± 0.74 -38.89 1096.97 ± 179.75 -37.11 Angelica: Mountain Garlic (4: 200 ms / ke 1.00 ± 0.53 -55.56 816.64 ± 301 · 07 -53.18 1) Complex composition 100 mg / kg 1.38 ± 0.52 -38.89 939.35 ± 277.97 -46.15 Administered group 50 me / ke 1.50 ± 0.53 -33.33 1162.96 ± 192.40 -33.33 As shown in Table 40, rats used as STZ controls were normal controls. Lens damage increased 800% compared to rats used, and the silymarin-treated group used as reference drug showed a 39% decrease in lens damage compared to STZ control group. In the combination composition 200, 100, and 50 mg / kg of the mixed weight ratio of Angelica extract and acid garlic extract, the ratio of lens damage was 33-56%, respectively, compared to the STZ control group.

In addition, as shown in Table 40, the rats used as the STZ control group had a 303% increase in the thickness of the lens injuries compared to the rats used as the normal control group, and the lens damage compared to the STZ control group in the silymarin-administered group used as the reference drug. The thickness of the site showed a 37% reduction. In the composite composition 200, 100 and 50 mg / kg of the composite weight ratio of Angelica extract and acid garlic extract, the thickness of the lens injury area was 33-58%, respectively, compared to the STZ control group.

(3) Histopathological changes in the retina

Tissue of Retinal Rats Induced Diabetes in order to Investigate the Effect of a Complex Composition of 4: 1 of Angelica Extract and Mountain Garlic Extract According to the Invention on Eye Protection of STZ-Induced Diabetic Animal Model The experimental results of the pathological changes are shown in Table 41 and Table 42 below.

Table 41 Histologic Changes in Tissue

Overall thickness STZ control Freeze layer thickness STZ control ("m / retina) (%) (am / retina) (%) Normal control Normal group 432.26 117.07 ± 16.24

STZ control ± 114.83

STZ 154.50 ± 31.03 -64.26 60.33 ± 11.58 -48.46

(Normal vs. Normal vs. Non) Control Psychiatric 237.65 ± 51.35 53.82 81.67 ± 14.14 35.37 Angelica: Mountain Garlic (4: 200 me / ke 296.92 ± 67.63 92.18 105.92 ± 6.50 75.57

100 mg / kg 247.38 ± 45.86 60.12 83.53 ± 13.81 38.45 1) Composite composition

Administration group 50 ms / e 223.91 ± 30.14 44.92 79.14 ± 10.29 31.18 As shown in Table 41, rats used as STZ controls had a 6 «reduction in total retinal thickness compared to rats used as controls. In the silymarin-treated group, the total thickness of the retina was increased by 5 «compared to the STZ control group. The total composition thickness of the retina was 45-92% in the composite composition 200, 100 and 50 mg / kg of the composite weight ratio of Angelica extract and acid garlic extract, respectively, compared to the STZ control group.

In addition, as shown in Table 41, the rats used as the STZ control group had a decrease in thickness of the retinal plexus layer by 48¾> compared to the rats used as the normal control group, and the retinal freezing group compared to the STZ control group in the silymarin-administered group used as the reference drug. The thickness of the worms showed a 35% increase. In the composite composition 200, 100 and 50 mg / kg of the composite weight ratio of Angelica extract and acid garlic extract, the thickness of the retinal frozen layer was 31-76%, respectively, compared to the STZ control group.

Table 42

Classification Tissue of ^t -shirt

The thickness of the nuclear layer STZ control Contrast present in the inner layer of STZ control (/ retina) compared to (>)

Vascular

Number of

retina)

Normal Control Normal Control 91.22 ± 9.07 1.25 ± 0.71

STZ control group STZ 42.45 -52.92 10.38 土 1.69 730.00

± 11.27 (compared to the normal group) compared to the control group psychotherapy 55.72 ± 8.64 29.74 5.25 ± 1.04 -49.40 Angelica sinensis: Mountain garlic (4: 200 mg / ke 68.09 ± 9.69 58.54 3.63 ± 0.74 -65.06 1) 100 mg / kg 64.36 49.86 5.13 ± 1.25 -50.60 Administration group ± 10.36

50 mg / ks 58.49 ± 8/78 36.19 5.63 ± 1.77 -45.78 As shown in Table 42, rats used as STZ controls had a 53% reduction in the thickness of the retinal nuclear layer compared to rats used as controls. In the silymarin administration group used, the thickness of the retinal nuclear layer was increased by 30% compared to the STZ control group. In the composite composition 200, 100 and 50 mg / kg of the composite weight ratio of Angelica extract and acid garlic extract, the thickness of the retinal nuclear layer was 36-59%, respectively.

In addition, as shown in Table 42, the rats used as the STZ control group had a 730% increase in the number of blood vessels present in the inner membrane of the retinal boundary membrane compared to the rats used as the normal control group. Compared to the control group, the number of blood vessels present in the inner retinal border membrane showed a 49% reduction. In the composite composition 200, 100 and 50 mg / kg of the mixed weight ratio of Angelica extract and acid garlic extract, the number of blood vessels in the inner membrane of the retinal boundary membrane was 46-65%, respectively, compared to the STZ control group. Indicated. As indicated above, typical diabetic eye damage, such as decreased retinal thickness, decreased thickness of the retinal sulcus and nucleus layer, and increased proliferation of the inner limiting membrane with increased cataract and lens injuries, was recognized in the STZ control group. Inhibition of cataract and eye damage is remarkably suppressed by the administration of all Angelica extract and Garlic extract complex It became. Therefore, the composite composition of Angelica extract and acid garlic extract according to the present invention was shown to effectively inhibit diabetic pathological ocular damage, and showed the same level of inhibitory effect on eye damage as silymarin at the same dose, thus preventing, treating and treating diabetes or diabetic complications. It can be usefully used as a composition for improvement.

In addition, the composite composition of the Angelica extract and acid garlic extract of the present invention has a relatively effective effect on diabetes and diabetic kidney damage, immunosuppression and eye damage by STZ administration, very effective in diabetes and related complications It is considered that the effective effect is recognized in the 50 mg / kg administration group, the optimal effective dose can be administered below 50 mg / kg, the composite composition of Angelica extract and acid garlic extract is equivalent to the same dose of silymarin as a whole Indicated.

Example 15 Toxicity Test of a Composite Composition Containing a Mixed Weight Ratio of Angelica Extract and Mountain Garlic Extract 4: 1

(1) experimental animals and methods

In order to obtain toxicity data for single dose oral administration of rats with a combined weight ratio of 4: 1 of Angelica extract and acid garlic extract according to the present invention, based on the Food and Drug Administration Notice 2009-116 "Toxicity of Drugs, etc." Thus, experiments were performed by setting the highest dose group for the rodent administration limit dose of 2000 mg / kg, and the 1000 and 500 mg / kg dose groups for the azeotropic ratio 2 as the medium and low dose dose groups. The experimental animals were male and female SD rats, and a total of 8 groups (including a media control group) were used for 5 animals in each group. The drug was orally administered using sterile distilled water as a solvent, and a single oral dose of 2000, 1000, 500 and 0 mg / kg.

(2) Experiment result

The results of the rat single oral administration toxicity test of the composite composition in which the combined weight ratio of the Angelica extract and the acid garlic extract according to the present invention are 4: 1 are shown below. death rate

As a result of the experiment, no deaths related to the administration of the composite composition with the combined weight ratio of the Angelica extract and the acid garlic extract of the present invention up to the 2000 mg / kg dose group of rodents did not occur during the 14-day experiment period. Weight and weight gain

In the composite composition administration group with the combined weight ratio of all donkey extract and wild garlic extract of 4: 1, significant body weight and weight gain did not occur during the pre-experiment period compared to the control group of the same gender. The change in weight gain of each group during the period is shown in Table ₄₃ below.

Table 43

Half lethal dose, rough lethal dose, target organ

In the present study, no mortality was recognized up to the 2000 mg / kg dose limit for rodents, so the single oral dose and the lethal dose for rats of the composite composition with the combined weight ratio of Angelica extract and wild garlic extract were 4: 1. Male and female were> 2000 mg / kg, and no specific clinical symptoms and target organs were observed. The results of the experiment are shown in Table 46 below.

Table 44

As shown in Table ₄ , as a result of a single oral dose toxicity test in rats of the composite composition of the Angelica extract and the garlic extract of the present invention with a combined weight ratio of 4: 1, mortality up to the 2000 mg / kg rodent dose limit was observed. In the two-week repeated dose setting experiment, the maximum dose of 2000 mg / kg was used as the highest dose, and 1000 and 500 mg / kg were used in the medium and low dose groups. It should be set as. <Example 16> micronucleus test of the composite composition of the mixed weight ratio of Angelica extract and acid garlic extract 4: 1

(1) experimental animals and methods

Mouse bone marrow cells were evaluated to evaluate the genotoxicity of a composite composition with a weight ratio of 4: 1 of the Angelica extract and acid garlic extract of the present invention selected as an optimal composition for obese diabetes and complications caused by high fat feeding. In vitro Vivo micronucleus experiments were performed.

As the experimental animals, 10 male animals were used per group of 5 male ICR mice (including the media control group and the positive control group -CPA administration group). The composite composition 2000, 1000 and 500 mg / kg of the mixed weight ratio of the Angelica extract and acid garlic extract of the present invention was 4: 1, dissolved in sterile distilled water, and orally administered once daily at 10 / kg for 2 days. Silver sterilized distilled water 10 / kg only was administered orally for 2 days, and the positive control group was intraperitoneally administered at 10m £ / k _g dissolved in 70 mg / kg CPA in saline (saline).

To date there are no oral mouse toxicity data for complex compositions of Angelica Extract and Mountain Garlic extract with a combined weight ratio of 4: 1, so the limit value for rodents (OECD Guidelines # 423, 2001; KFDA Guidelines 2009-116, 2009) mg / kg was set to the highest dose, 1000 and 500 mg / kg dose groups were set at azeotropic 2 according to KFDA Guideline (2009-116, 2009), and the appropriate dose for single oral administration of mice (Flecknell, Laboratory Animal Anesthesia, 2nd Ed, p 269, 1996) was administered orally once a day for 2 days at a dose of 10 mi / kg.

(2) Experiment result

The micronucleus test results of the composite composition with the mixed weight ratio of Angelica extract and acid garlic extract are shown below. death rate

As a result of the experiment, there were no deaths related to the administration of the composite composition of the Angelica extract and the garlic extract, and no death occurred in the control group and the CPA group. Congestion and Weight Gain No significant change in body weight and weight gain occurred in the CPA or the composite composition-administered group having a combined weight ratio of 4: 1 of the Angelica extract and acid garlic extract of the present invention. Numerical changes in micronucleus polychromatic erythrocyte (MNPCE) micronucleus tests using mouse bone marrow smears are the simplest and most reliable assessment of genotoxicity (Renner, Mutat Res. 1990; 244: 185-8). In addition, an increase in micronucleated polycytic erythrocytes represents a potential for genotoxicity. As a result of this experiment, the composite composition with the combined weight ratio of Angelica extract and wild garlic extract showed a numerical change of MNPCE similar to that of the medium control group up to 2000 mg / kg of rodent maximum dose. It was confirmed that the micronucleus experiment using the negative. The numerical changes of micronucleated red blood cells of each group are shown in Table 45 below.

Table 45

Representative drug (Grochow, Williams &Wilkins;1996; 293–316), known to cause hematopoietic and lymphoid cell damage, resulting in significant leukopenia (Angulo et al., Blood. 2000; 95; : 212-20). Alkylating nucleic acids, a metabolite of CPA (Miyauchi et al., Tohoku J Exp Med. 1990; 162: 147-67), form free-radicals and alkylate 匪 to inherit It is known to cause mutagenici ty (El-Bayoumy, Mutat Res. 2001; 475: 123-39), and is currently notified by the Korea Food and Drug Administration (Toxicological Standards of Drugs, 2009-116, 2009). Is recommended as a positive control in micronucleus testing using mouse bone marrow cells. In the present experiment, the CPA 70 mg / kg administration group showed a significant increase in micronucleitis erythrocytes compared to the medium control group, and this experiment was performed relatively well. Changes in the percentage of polyinflammatory red blood cells (PCE (PCE + NCE normochromatic erythrocyte))

The ratio of polyinflammatory erythrocytes (PCE / (PCE + NCE)) is an indicator of cytotoxicity of treated substances. (Heddle et al., Handbook of Mutagenicity Test Procedures. 2nd Edion, Elsevier, pp. 441-57, 1984). As a result of this experiment, it was found that the PCE / (PCE + NCE) ratio and PCE / (PCE + NCE) ratio were significantly reduced compared to the control group. NCE) ratio was observed above 0.47 on average (individual: above 0.44), so there is no error due to cytotoxicity. The change in the ratio of polyinflammatory red blood cells in each group is shown in Table 48 below.

Table 46

The composite composition with a common increase ratio of 4: 1 extract did not show any significant change in MNPCE up to the 2000 mg / kg rodent limit dose and was negative in micronucleus experiments using bone marrow cells. Hereinafter, the preparation examples of the pharmaceutical composition including the extract of the present invention will be described, but the present invention is not intended to be limited thereto, but is intended to be described in detail.

Preparation Example 1 Preparation of Pharmaceutical Formulation

1-1. Manufacture of powder

Angelica and Garlic Extract 500 mg

Lactose 100 mg

Talc 10 mg Powders are prepared by combining the above ingredients and filling in airtight sachets.

1-2. Manufacture of tablets

Angelica and Garlic Extract 500 mg

Corn starch 100 mg

O

100 mg per ΤΓ

2 mg magnesium stearate After mixing the above components and tableting according to the conventional manufacturing method of the tablet to prepare a tablet.

1-3. Manufacture of capsule

Angelica and Garlic Extract 500 mg

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg A capsule preparation is prepared by mixing the above ingredients according to a conventional capsule preparation method and filling into gelatin capsules.

1-4. Preparation of Injectables

Angelica and mountain garlic complex composition

Sterile Distilled Water for Injection

H Modifier According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 m ^).

1-5. Preparation of liquid

Angelica and wild garlic complex composition 100 mg

10 g of isomerized sugar

5 g of Manni

Appropriate amount of purified water Dissolve each of the ingredients in purified water according to the usual method of preparing liquid solution, add the lemon flavor appropriately, mix the above ingredients, add purified water, adjust the whole to purified water, and adjust the total amount to 100. Layered and sterilized to prepare a liquid. Preparation Example 2 Preparation of Health Food

Angelica and Garlic Extract 1000 mg

Vitamin Complex Proper

Vitamin A Acetate 70 μ

Vitamin E 1.0 mg

0.13 mg of vitamin

Vitamin 0.15 mg Vitamin B ₆ 0.5 mg Vitamin B ₁₂ 0.2 Vitamin C 10 mg

Biotin 10 iig

Nicotinamide 1.7 rag

Folic acid 50 iig

Calcium Pantothenate 0.5 mg

Mineral Mixtures Proper

Ferrous Sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

15 mg potassium monophosphate

Dicalcium Phosphate 55 mg

Potassium Citrate 90 mg

Calcium Carbonate 100 mg

Magnesium chloride 24.8 mg The composition ratio of the vitamin and mineral mixtures described above is a relatively suitable composition for the health food in a preferred embodiment, but the formulation ratio may be arbitrarily modified, according to the conventional health food manufacturing method After mixing the components, the granules may be prepared and used for preparing a health food composition according to a conventional method.

Preparation Example 3 Preparation of Healthy Drinks

Angelica and Garlic Extract 1000 mg Citric acid 1000 mg

100 g oligosaccharides

Plum concentrate 2 g

1 g of taurine

After adding purified water, the above ingredients were mixed according to the general method of preparing a healthy beverage, and then stirred and heated at 85 ^° C. for about 1 hour, and then the resulting solution was filtered and obtained in a sterilized 2I container. After sealing sterilization and refrigerated, it was used to prepare a healthy beverage composition. Although the composition ratio is a relatively suitable composition for the preferred drink in a preferred embodiment, the compounding ratio may be arbitrarily modified according to regional and national preferences such as demand hierarchy, demand country, and usage.

Preparation Example 4 Preparation of Other Health Foods

4-1. Manufacture of beverages

522 mg of honey

Chioctosanamide 5 rag

Nicotinic Acid 10 mg

Riboflavin Sodium Hydrochloride 3 mg

Pyridoxine hydrochloride 2 mg

30 nig ino city

Ort acid 50 nig

Angelica and Garlic Extract 0.48-1.28 mg

200 A beverage was prepared using conventional methods with the above composition and content.

4-2. Preparation of Chewing Gum

Gum Base 20%

Sugar 76.36-76.76%

Angelica and Mountain Garlic Composition 0.24-0.64%

1% of fruit flavor Chewing ¾ was prepared using conventional methods using the composition and content of 2%.

4-3. Candy

50-60% sugar

Starch syrup 39.26-49.66%

Angelica and Mountain Garlic Composition 0.24-0.64%

Orange Flavor 0.1% Candy was prepared using a conventional method with the composition and content. 4-4. Manufacture of Flour Food

0.5-5 parts by weight of the composite composition of Angelica and wild garlic was added to 100 parts by weight of wheat flour, and bread, cake, cookies, crackers, and noodles were prepared using the mixture to prepare health-promoting foods.

4-5. Manufacture of dairy products

5-10 parts by weight of the Angelica sinensis and wild garlic complex composition were added to 100 parts by weight of milk, and various dairy products such as butter and ice cream were prepared using the milk.

4-6. Manufacture of wire

Brown rice, barley, red rice, and yulmu were alphanized by a known method to distribute the dried ones, and then prepared into a powder having a particle size of 60 mesh. Black beans, black sesame seeds, and perilla were also roasted by steaming in a known manner, and then prepared into a powder having a particle size of 60 mesh. The grains and seeds prepared above, and the composite composition of Angelica and wild garlic of the present invention were prepared by combining the following ratios. 30% brown rice

15% rate

Barley 20%

Perilla 7% Black Bean 7% Black Sesame Soup Angelica and Mountain Garlic Composition 3% Ganoderma 0.5% Foxglove 0.5%

Claims

[Range of request]

[Claim 1]

A pharmaceutical composition for preventing or treating diabetic or diabetic complications, comprising as an active ingredient a complex herbal extract having a weight ratio of 1: 4-6 or 2-4: 1.

[Claim 2]

The pharmaceutical composition for preventing or treating diabetes or diabetic complications of claim 1, wherein the weight ratio of the Angelica extract and the garlic extract is 1: 4 or 4: 1.

[Claim 3]

The pharmaceutical composition for preventing or treating diabetes or diabetic complications according to claim 1, wherein an increase ratio of the Angelica extract and the garlic extract is 4: 1.

[Claim 4]

The pharmaceutical composition for preventing or treating diabetes or diabetic complications of claim 1, wherein the composition exhibits anti-obesity activity.

[Claim 5]

The pharmaceutical composition for preventing or treating diabetes mellitus or diabetic complications of claim 1, wherein the composition exhibits hypoglycemic activity.

[Claim 6]

The pharmaceutical composition for preventing or treating diabetes or diabetic complications according to claim U, wherein the composition exhibits antihyperlipidemic activity.

[Claim 7]

According to claim 1, wherein the composition is a pharmaceutical composition for the prevention or treatment of diabetes or diabetes complications, characterized in that hepatoprotective activity.

[Claim 8] The method of claim 1, wherein the composition is a pharmaceutical composition for the prevention or treatment of diabetes or diabetes complications, characterized in that exhibiting renal protective activity.

[Claim 9]

The pharmaceutical composition for preventing or treating diabetes or diabetic complications of claim 5, wherein the composition exhibits immunosuppressive protective activity.

[Claim 10]

The pharmaceutical composition for preventing or treating diabetes mellitus or diabetic complications according to claim U, wherein the composition exhibits eye damage protection activity.

[Claim 11]

The pharmaceutical composition for preventing or treating diabetes mellitus or diabetic complications of claim 1, wherein the diabetes is type 2 diabetes.

[Claim 12]

The method of claim U, wherein the diabetic complication is diabetes selected from the group consisting of diabetic nephropathy, diabetic liver cirrhosis, hypertension, atherosclerosis, stroke, heart failure, immunosuppression and diabetic retinopathy Pharmaceutical compositions for the prevention or treatment of diabetic complications.

[Claim 13]

A pharmaceutical composition for the prevention or treatment of obesity diseases, which contains a complex herbal extract having a weight ratio of Angelica extract and acid garlic extract at 1: 4-6 or 2-4: 1 as an active ingredient.

[Claim 14]

The pharmaceutical composition for preventing or treating obesity disease according to claim 11, wherein the weight ratio of the Angelica extract and the garlic extract is 1: 4 or 4: 1.

[Claim 15]

12. The method according to claim 11, wherein the weight ratio of Angelica extract and garlic extract is 4: 1 Pharmaceutical composition for the prevention or treatment of obesity diseases, characterized in that.

[Claim 16]

The composition of claim 1, wherein the effect of preventing or treating diabetes or diabetic complications is caused in a dose-dependent manner.

[Claim 17]

The composite composition of Angelica extract and acid garlic extract according to claim 1, wherein the prophylactic or therapeutic effect of obesity disease is caused in a dose-dependent manner.

[Claim 18]

A health food composition for preventing or improving diabetes or diabetic complications, comprising as an active ingredient a complex herbal extract having a weight ratio of Angelica extract and acid garlic extract 1: 4-6 or 2-4: 1.

[Claim 19]

15. The healthy food composition of claim 14, wherein the weight ratio of the Angelica extract and the garlic extract is 1: 4 or 4: 1.

[Claim 20]

15. The health food composition for preventing or improving diabetes or diabetes complications according to claim 14, wherein the weight ratio of the Angelica extract and the garlic extract is 4: 1.

[Claim 21]

15. The health food composition for preventing or improving diabetes or diabetic complications according to claim 14, wherein the composition exhibits anti-obesity activity.

[Claim 22]

15. The health food composition for preventing or improving diabetes or diabetic complications according to claim 14, wherein the composition exhibits hypoglycemic activity.

[Claim 23]

15. The health food composition of claim 14, wherein the composition exhibits antihyperlipidemic activity.

[Claim 24]

The health food composition for preventing or improving diabetes or diabetic complications of claim 14, wherein the composition exhibits liver protective activity.

[Claim 25]

15. The health food composition for preventing or ameliorating diabetes or diabetic complications according to claim 14, wherein the composition exhibits renal protective activity.

[Claim 26]

15. The health food composition for preventing or improving diabetes or diabetic complications of claim 14, wherein the composition exhibits immunosuppressive protective activity.

[Claim 27]

15. The health food composition of claim 14, wherein the composition exhibits eye damage protection activity.

[Claim 28]

15. The health food composition of claim 14, wherein the diabetes is crab type 2 diabetes.

[Claim 29]

15. The method according to claim 14, wherein the diabetic complication is a disease selected from the group consisting of diabetic nephropathy, diabetic liver cirrhosis, hypertension, atherosclerosis, stroke, heart failure, immunosuppression and diabetic retinopathy. Health food composition for preventing or improving diabetes complications.

[Claim 30] Health food composition for the prevention or improvement of obesity diseases containing complex herbal extracts in which the weight ratio of Angelica extract and mountain garlic extract is 1: 4-6 or 2-4: 1 as an active ingredient

[Claim 31]

The health food composition for preventing or improving obesity disease according to claim 24, wherein the weight ratio of the Angelica extract and the garlic extract is 1: 4 or 4: 1.

[Claim 32]

25. The health food composition for preventing or improving obesity disease according to claim 24, wherein the weight ratio of the Angelica extract and the garlic extract is 4: 1.

[Claim 33]

A method of treating diabetes mellitus or diabetic complications comprising administering to a subject in need thereof an effective dose of a composite herbal extract having a weight ratio of Angelica extract and acid garlic extract in a ratio of 1: 4-6 or 2-4: 1.

[Claim 34]

A method of treating obesity disorders comprising administering to a subject in need thereof an effective dose of a composite herbal extract having a weight ratio of Angelica extract and garlic extract to 1: 4-6 or 2-4: 1.