KR20210157522A - Composition for preventing, ameliorating or treating diabetic nepropathy comprising bangpungtongseongsan extract as effective component - Google Patents

Abstract

The present invention relates to a composition for preventing, alleviating or treating diabetic nephropathy comprising an extract of Bojungikgi-Tang as an active ingredient. More particularly, the present invention relates to a pharmaceutical composition for preventing or treating diabetic nephropathy, and a food composition for preventing or alleviating diabetic nephropathy, which comprises an extract of Bojungikgi-Tang consisting of Astragalus Membranaceus, ginseng, Atractylodis rhizoma, licorice, Angelica gigas, Citrus unshiu, Cimicifuga heracleifolia Komarov, Bupleurum falcatum, dried root of Zingiber officinale, and jujube as active ingredients. A composition containing an extract of Bojungikgi-Tang according to the present invention reduces blood urea nitrogen and creatinine levels and alleviates kidney tissue damage and kidney fibrosis when applied to an animal model of type 2 diabetic nephropathy, and thus can be advantageously used for pharmaceuticals, food and the like for preventing, alleviating or treating diabetic nephropathy.

Description

A composition for preventing, improving or treating diabetic nephropathy comprising an extract of Bojungikgi-tang as an active ingredient TECHNICAL FIELD

The present invention relates to a composition for preventing, improving or treating diabetic nephropathy, comprising the extract of Bojungikgi-tang as an active ingredient. More specifically, a pharmaceutical composition for preventing or treating diabetic nephropathy comprising an extract of bojungikgi-tang consisting of astragalus, ginseng, baekchul, licorice, angelica, dermis, horseback riding, shiho, health and jujube as an active ingredient, and diabetes It relates to a food composition for preventing or improving sexual nephropathy.

When diabetes persists for a long time, small blood vessels in the body are damaged. When blood vessels in the kidney are damaged, the glomeruli responsible for blood filtration are damaged, resulting in proteinuria, which leads to a decrease in kidney function, which is called diabetic nephropathy (DN). Diabetic nephropathy is one of the serious problems in diabetic people, and about 10-30% of patients diagnosed with diabetes after the age of 30 develop renal failure in which the kidneys do not function properly 20 years after diagnosis.

Since diabetic nephropathy starts with the onset of hyperglycemia and progresses very slowly, the patient himself/herself may not feel any special symptoms even if it has progressed to some extent. When diabetic nephropathy is advanced and proteinuria is detected severely in urinalysis, swelling of the face, eyes, hands, and ankles, or frequent urination at night are often accompanied. When diabetic nephropathy worsens and progresses to end-stage renal failure, in which the kidneys almost lose their ability to filter waste from the body, the level of waste products, urea nitrogen and creatinine, in the blood rises as the renal function declines. Patients experience symptoms such as nausea, vomiting, loss of appetite, weakness, fatigue, itchiness, and muscle cramps.

In the treatment of diabetic nephropathy, since a cell or tissue disorder due to a chronic hyperglycemic state is the root cause of the disease, strict blood sugar control is first performed with various oral hypoglycemic agents.

In addition, it is known that diabetic nephropathy involves various mechanisms related to disorders of cells or kidney tissues caused by hyperglycemia. As mechanisms that may be involved, polyol metabolic pathway, hexosamine pathway, protein kinase C pathway, oxidative stress and final glycation products have been reported in the intracellular metabolic level, and renin angiotensin system (RAS) in kidney tissue , TGF-β, etc. have been reported. Since various mechanisms or factors are related to form the condition of diabetic nephropathy, it is considered that these mechanisms or factors are likely to be therapeutic targets in the treatment of diabetic nephropathy.

On the other hand, Bojungikgi-tang (補中益气湯) is described as follows as three different ingredients in the Dictionary of Oriental Medicine.

), 일련의 출혈 등에 쓸 수 있다. 위의 약을 1첩으로 하여 물에 달여서 먹거나 가루 내어 꿀로 환제를 만들어 한 번에 8~12g씩 하루 3번 먹기도 한다.① Hwangki (黃耆) 6g, ginseng (人參), baekchul (白朮), licorice (甘草) 4g each, Angelica root, dermis 2g each, horseback riding (升麻), Shiho (柴胡) 1.2 each It is composed of g (Donguibogam (東醫寶鑑)) and the whole body is tired from giheo fever (气虛發熱), a slight fever every afternoon, a cold sweat, a headache, loss of appetite, severe cold, or中气下陷) with the above-mentioned symptoms, the lower abdomen is dull and often watery stools, prolapse, uterine prolapse, etc. is used. Chronic wasting disease including tuberculosis disease, visceral sewage including gastritis, summer riding, chronic colitis, umbilical cord (

), a series of bleeding, etc. can be used. You can take the above medicine by decocting it in water or making powdered pills with honey, 8~12g at a time, 3 times a day.

② Ginseng, Saengjihwang (生地黃), Hwanggi (黃耆), Angelica (當歸), Cheongung (Stream), Shiho (柴胡), Dermal (陳皮), Ganghwa (羌活), Baekchul (白朮), Windbreak Consists of 2.8g each, finestain (細辛), licorice (甘草) 2g each, ginger (生薑) 3 cloves, and contrasting (大棗) 2 pieces (Donguibogam), qi blood血) is not enough, I have a cold, a fever, a headache, a cold sweat, it's cold, I'm very tired and I don't have energy. Take 1 tablet of the above medicine, decocted in water. It is also called Dosibojungikgitang (陶氏補中益气湯).

③ Ginseng (人參), Hwanggi (黃耆) 12g each, Baekchul (白朮), Angelica (當歸), ginseng (陳皮), licorice (甘草) 4g each, Perilla leaves, Kwakhyang 2g each (Sasang Medical Clinic), as a prescription for soeumin (少陰人), in the early days of mangyang for sun-disease, and the body is very tired and low in energy, but the body is weak. It is used for fever, chest tightness, and cold sweats while doing this. Take 1 tablet of the above medicine, decocted in water.

In addition, Korean Patent No. 10-1332829 discloses a composition for treating lung cancer containing Bojungikgi-tang, and Korean Patent Registration No. 10-1740021 discloses a composition for enhancing the therapeutic effect of thyroid dysfunction including Bojungikgi-tang. and Korean Patent No. 10-1866553 discloses a composition for treating dementia comprising Bojungikgi-tang, and Korean Patent Publication No. 10-2004-0103984 discloses a composition containing an extract of Bojungikgi-tang or an extract of Gagam-Bojungikgi-tang. Disclosed is a pharmaceutical composition for the treatment of inflammation. However, there is no disclosure of a composition for preventing, improving or treating diabetic nephropathy comprising the Bojungikgi-tang extract of the present invention as an active ingredient.

Korean Patent Registration No. 10-1332829 (2013.11.27. Announcement) Korean Patent Registration No. 10-1740021 (2017.05.25. Announcement) Korean Patent Registration No. 10-1866553 (2018.07.17. Announcement) Korean Patent Publication No. 10-2004-0103984 (published on Dec. 10, 2004)

An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of diabetic nephropathy comprising the extract of Bojungikgi-tang as an active ingredient.

Another object of the present invention is to provide a food composition for preventing or improving diabetic nephropathy comprising the extract of Bojungikgi-tang as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical for the prevention or treatment of diabetic nephropathy comprising, as an active ingredient, a bojungikgi-tang extract consisting of astragalus, ginseng, baekchul, licorice, angelica, dermis, horseback riding, shiho, health and jujube. Provides an enemy composition.

In addition, the present invention provides a food composition for preventing or improving diabetic nephropathy comprising, as an active ingredient, a bojungikgi-tang extract consisting of astragalus, ginseng, baekchul, licorice, angelica, dermis, horseback riding, shiho, health and jujube.

The composition comprising the Bojungikgi-tang extract of the present invention, more specifically, the Bojungikgi-tang water extract consisting of astragalus, ginseng, baekchul, licorice, angelica, dermis, horseback riding, shiho, health and jujube as an active ingredient, is an animal with type 2 diabetes complications. When applied to the model, it reduces the concentration of blood urea nitrogen and creatinine, and improves kidney tissue damage and kidney fibrosis, so it can be usefully used in pharmaceuticals and foods for the prevention, improvement or treatment of diabetic nephropathy.

1 is a road showing the effect of the Bojungikgi-tang water extract of the present invention on the renal function index in an animal model of type 2 diabetes complications, and the concentration of creatinine (A) and blood urea nitrogen (B) using a blood biochemical analyzer. It is a graph showing the measurement.
2 is a road showing the effect of the Bojungikgi-tang water extract of the present invention on damage to kidney tissue in an animal model of complications of type 2 diabetes, and is a micrograph of the degree of damage to kidney tissue by H&E staining.
Figure 3 is a road showing the effect of the Bojungikgi-tang water extract of the present invention on renal fibrosis in an animal model of type 2 diabetes complications. A micrograph and image of the degree of renal fibrosis by staining with Peak Serious Red. Stained with the J program. This is a histogram displayed by analyzing color intensity.

As a result of the present inventors diligent efforts to find a natural product with few side effects while exhibiting a preventive, ameliorating or therapeutic effect on diabetic nephropathy, the concentration of blood urea nitrogen and creatinine was reduced when the Bojungikgi-tang water extract was applied to an animal model of type 2 diabetes complications. By confirming the improvement or therapeutic effect of diabetic nephropathy, such as improving renal tissue damage and renal fibrosis, the present invention has been completed.

As an aspect, the present invention provides a pharmaceutical for preventing or treating diabetic nephropathy, comprising, as an active ingredient, a bojungikgi-tang extract consisting of astragalus, ginseng, baekchul, licorice, angelica, dermis, horseback riding, shiho, health and jujube. A composition is provided.

As used herein, the term "Bojungikgi-tang (防防防通性散)" is a herbal prescription for decoction and drinking together with astragalus, ginseng, baekchul, licorice, angelica, dermis, horseback riding, shiho, health and jujube.

The term "diabetic nephropathy" is one of the chronic microvascular complications of diabetes, in which small blood vessels of the kidney are damaged and proteins are excreted in the urine, and as it progresses further, waste products cannot be gradually excreted, leading to chronic renal failure. it's sick Progression to chronic renal failure is characterized by end-stage changes, nephron destruction and fibrosis. It is also known that when diabetic nephropathy worsens and progresses to end-stage renal failure, in which the kidneys almost lose their ability to filter out wastes in the body, the levels of urea nitrogen and creatinine, which are waste products in the blood, increase as the renal function declines.

The term "extract" in the present invention refers to a liquid component obtained by immersing a target substance in various solvents and then extracting it for a certain time at room temperature or in a heated state, and a solid obtained by removing the solvent from the liquid component. results, etc. In addition, in addition to the result, it can be comprehensively interpreted as including all of the dilutions of the results, their concentrates, their preparations, and their purified products.

In the present invention, the extract means a bojungikgi-tang extract consisting of astragalus, ginseng, baekchul, licorice, angelica, dermis, horseback riding, shiho, health and jujube.

The bojungikgi-tang extract is not limited thereto, but 22 to 26% by weight of astragalus, 15 to 18% by weight of ginseng, 15 to 18% by weight of baekchul, 15 to 18% by weight of licorice, 7 to 9% by weight of angelicasis, 7 to 9% by weight of dermis It may be a mixed extract of 4 to 5.5% by weight of horseback riding, 4 to 5.5% by weight of Shiho, 2 to 4 pages of health, and 1 to 3 jujubes.

The bojungikgi-tang extract is preferably 23 to 26% by weight of Astragalus, 15.5 to 17% by weight of ginseng, 15.5 to 17% by weight of baekchul, 15.5 to 17% by weight of licorice, 7.5 to 8.5% by weight of Angelica Root, 7.5 to 8.5% by weight of dermis, It may be a mixed extract of 4.5 to 5.5% by weight of horseback riding, 4.5 to 5.5% by weight of Shiho, 2 to 4 pages of health, and 1 to 3 jujubes.

The Bojungikgi-tang extract is more preferably 24 to 25% by weight of astragalus, 16 to 17% by weight of ginseng, 16 to 17% by weight of baekchul, 16 to 17% by weight of licorice, 8 to 8.5% by weight of angelicasis, 8 to 8.5% by weight of dermis It may be a mixed extract of 3% by weight, 4.6 to 5.2% by weight of horseback riding, 4.6 to 5.2% by weight of Shiho, 3 pyeonyi and 2 jujubes.

The bojungikgi-tang extract is more preferably astragalus 24.6% by weight, ginseng 16.4% by weight, baekchul 16.4% by weight, licorice 16.4% by weight, Angelica 8.2% by weight, dermis 8.2% by weight, horseback riding 4.9% by weight, Shiho 4.9% by weight It may be a mixed extract of 3 p. , health and 2 jujubes.

The Bojungikgi-tang extract can be obtained by extraction with water or various organic solvents. At this time, the organic solvent used is not particularly limited as long as an extract having a preventive or therapeutic effect for diabetic nephropathy can be obtained, but preferably water, a polar solvent or a non-polar solvent, and more preferably may be water, a lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol or butanol, etc.), a mixed solvent thereof, etc., and most preferably water.

In addition, the method for obtaining the extract is also not particularly limited thereto, as long as an extract having a preventive or therapeutic effect for diabetic nephropathy can be obtained, but preferably the astragalus, ginseng, baekchul, licorice, angelica, dermis , horseback riding, shiho, health and jujube, immersed in the solvent, that is, water, and heated to 90 to 110 ℃, preferably 105 ℃ heat extraction method can be used for extraction. On the other hand, the extraction time is preferably 3 to 12 hours, more preferably 4 to 8 hours, and most preferably 5 hours, but is not limited thereto. In addition, the number of extractions is preferably 1 to 5 times, more preferably repeating extraction 1 to 3 times, and most preferably 2 times, but is not limited thereto.

The obtained Bojungikgi-tang hot water extract is not limited thereto, but may be concentrated under reduced pressure using a vacuum concentrator or a vacuum rotary evaporator. In addition, after concentration under reduced pressure, but not limited thereto, it may be dried through freeze drying, reduced pressure drying, vacuum drying, boiling drying, or spray drying.

The term "prevention" in the present invention means any action that inhibits or delays the onset of diabetic nephropathy by administration of the pharmaceutical composition according to the present invention, and "treatment" means diabetes by administration of the pharmaceutical composition. It refers to any action in which the symptoms of the suspected or affected individual of sexual nephropathy are improved or are changed to a beneficial effect.

In the present invention, the prevention or treatment of diabetic nephropathy reduces the concentration of blood urea nitrogen and creatinine in an animal model of type 2 diabetic complications by the extract, and significantly reduces kidney tissue damage and kidney fibrosis. may be achieved by

The term “fibrosis” refers to the hardening of a part of an organ. Renal fibrosis is a common phenomenon seen in all kidney diseases transitioning to chronic kidney disease. It is known to be caused by proteolytic regulatory enzymes and the like.

As described above, the Bojungikgi-tang extract provided by the present invention can reduce the concentrations of blood urea nitrogen and creatinine in an animal model of type 2 diabetes complications, and improve kidney tissue damage and kidney fibrosis.

In one embodiment of the present invention, in order to confirm the improvement or therapeutic effect of the water extract of Bojungikgi-tang for diabetic nephropathy, the concentration of blood urea nitrogen and creatinine in the animal model of type 2 diabetes complications; In addition, as a result of analyzing the extent of kidney tissue damage and renal fibrosis through H&E staining and Picro sirius red staining, respectively, the results showed that Bojungikgi-tang water extract reduced the concentration of blood urea nitrogen and creatinine, and It was found that damage and renal fibrosis were significantly improved ( FIGS. 1 to 3 ).

In addition to the Bojungikgi-tang extract, which is the active ingredient of the composition of the present invention, other useful diabetic nephropathy treatment drugs, such as hypoglycemic agents, angiotensin converting enzyme inhibitors, and the like may be formulated and administered in a mixed formulation.

The composition of the present invention may be used alone or in combination with methods such as hemodialysis or peritoneal dialysis for the prevention or treatment of diabetic nephropathy.

The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier, excipient and diluent. As used herein, the term “pharmaceutically acceptable” refers to exhibiting non-toxic properties to cells or humans exposed to the composition. The carrier may be used without limitation as long as it is known in the art, such as buffers, preservatives, pain relievers, solubilizers, isotonic agents, stabilizers, bases, excipients, lubricants, and the like.

In addition, the pharmaceutical composition of the present invention is formulated in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups and aerosols, external preparations, suppositories, and sterile injection solutions according to conventional methods, respectively. can be used Carriers, excipients and diluents that may be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, it is prepared using commonly used diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid preparations include at least one excipient in the Bojungikgi-tang extract, for example, starch, calcium carbonate, sucrose It is prepared by mixing sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid formulations for oral use include suspensions, solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients, for example, wetting agents, sweeteners, fragrances, preservatives, etc. may be included. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As a base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like can be used.

On the other hand, the pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. As used herein, the term "administration" means introducing a predetermined substance to an individual by an appropriate method, and the administration route of the composition may be administered through any general route as long as it can reach a target tissue. Intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, topical administration, intranasal administration, intrapulmonary administration, may be administered intrarectally, but is not limited thereto.

The term “individual” refers to all animals including humans, mice, mice, and livestock. Preferably, it may be a mammal including a human.

The term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment and not to cause side effects, and the effective dose level is determined by the patient's gender, age, and weight. , health condition, disease type, severity, drug activity, sensitivity to drug, administration method, administration time, administration route, and excretion rate, treatment period, factors including drugs used in combination or concomitantly, and other medical fields. It can be readily determined by one of ordinary skill in the art according to known factors. However, for a desirable effect, for adults, the composition of the present invention may contain 1 to 4000 mg/kg (body weight) as a single dose. For administration, the recommended dosage may be administered once a day, or may be administered in several divided doses.

Meanwhile, the Bojungikgi-tang extract in the composition may be included in an amount of 100 to 2000 mg/kg, 120 to 1500 mg/kg, or 150 to 1500 mg/kg based on oral administration to a mouse.

The above dosage does not limit the scope of the present invention in any way.

As another aspect, the present invention is a food for preventing or improving diabetic nephropathy, comprising, as an active ingredient, a bojungikgi-tang extract consisting of astragalus, ginseng, baekchul, licorice, angelica, dermis, horseback riding, shiho, health and jujube. A composition is provided.

The bojungikgi-tang extract is not limited thereto, but 22 to 26% by weight of astragalus, 15 to 18% by weight of ginseng, 15 to 18% by weight of baekchul, 15 to 18% by weight of licorice, 7 to 9% by weight of angelicasis, 7 to 9% by weight of dermis It may be a mixed extract of 4 to 5.5% by weight of horseback riding, 4 to 5.5% by weight of Shiho, 2 to 4 pages of health, and 1 to 3 jujubes.

The bojungikgi-tang extract is preferably 23 to 26% by weight of Astragalus, 15.5 to 17% by weight of ginseng, 15.5 to 17% by weight of baekchul, 15.5 to 17% by weight of licorice, 7.5 to 8.5% by weight of Angelica Root, 7.5 to 8.5% by weight of dermis, It may be a mixed extract of 4.5 to 5.5% by weight of horseback riding, 4.5 to 5.5% by weight of Shiho, 2 to 4 pages of health, and 1 to 3 jujubes.

The Bojungikgi-tang extract is more preferably 24 to 25% by weight of astragalus, 16 to 17% by weight of ginseng, 16 to 17% by weight of baekchul, 16 to 17% by weight of licorice, 8 to 8.5% by weight of angelicasis, 8 to 8.5% by weight of dermis It may be a mixed extract of 3% by weight, 4.6 to 5.2% by weight of horseback riding, 4.6 to 5.2% by weight of Shiho, 3 pyeonyi and 2 jujubes.

The bojungikgi-tang extract is more preferably astragalus 24.6% by weight, ginseng 16.4% by weight, baekchul 16.4% by weight, licorice 16.4% by weight, Angelica 8.2% by weight, dermis 8.2% by weight, horseback riding 4.9% by weight, Shiho 4.9% by weight It may be a mixed extract of 3 p. , health and 2 jujubes.

The Bojungikgi-tang extract can be obtained by extraction with water or various organic solvents. At this time, the organic solvent used is not particularly limited as long as an extract having a preventive or therapeutic effect for diabetic nephropathy can be obtained, but preferably water, a polar solvent or a non-polar solvent, and more preferably may be water, a lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol or butanol, etc.), a mixed solvent thereof, etc., and most preferably water.

The Bojungikgi-tang extract and the improvement effect thereof on diabetic nephropathy are the same as described above, and when the composition of the present invention is used as a food additive, the Bojungikgi-tang extract can be added as it is or used with other foods or food ingredients, , can be appropriately used according to a conventional method. The mixing amount of the active ingredient may be suitably determined according to the purpose of use (prevention, health or therapeutic treatment), and may further include a food pharmaceutically acceptable food supplement additive. Since the composition of the present invention uses an extract derived from a natural product and a fraction thereof as an active ingredient, there is no problem in terms of stability, so there is no great limitation on the mixing amount.

The food composition of the present invention may include all foods in a conventional sense, and may be used interchangeably with terms known in the art, such as functional food and health functional food.

As used herein, the term "functional food" refers to food manufactured and processed using raw materials or ingredients useful for the human body according to Health Functional Food Act No. 6727, and "functionality" refers to the structure of the human body. And it means ingestion for the purpose of obtaining useful effects for health purposes such as regulating nutrients for function or physiological action.

In addition, the term "health functional food" as used in the present invention refers to a food manufactured and processed using a specific ingredient as a raw material or by extracting, concentrating, refining, or mixing a specific ingredient contained in the food raw material for the purpose of health supplementation, It refers to a food designed and processed to sufficiently exert biological control functions such as biological defense, regulation of biological rhythm, prevention and recovery of disease, etc., by the above ingredients, and the composition for health food is used for prevention of diseases and prevention of diseases. It can perform functions related to recovery, etc.

There is no limitation on the kind of food in which the composition of the present invention can be used. In addition, the composition comprising the Bojungikgi-tang extract of the present invention as an active ingredient can be prepared by mixing other suitable auxiliary ingredients that may be contained in food and known additives according to the selection of those skilled in the art. Examples of foods that can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages and There are vitamin complexes and the like, and it can be prepared by adding the extract according to the present invention and a fraction thereof as a main component to juice, tea, jelly, juice, and the like.

In addition, foods that can be applied to the present invention include, for example, special nutritional foods (eg, formula milk, infant food, etc.), processed meat products, fish meat products, tofu, jelly, noodles (eg, ramen, noodles, etc.), health supplements , Seasoned foods (eg soy sauce, soybean paste, red pepper paste, mixed soy sauce, etc.), sauces, sweets (eg snacks), dairy products (eg fermented milk, cheese, etc.), other processed foods, kimchi, pickled foods (various kimchi, pickles, etc.) ), beverages (eg, fruit, vegetable beverages, soy milk, fermented beverages, etc.), and natural seasonings (eg, ramen soup, etc.).

When the health functional food composition of the present invention is used in the form of a beverage, it may contain various sweetening agents, flavoring agents, or natural carbohydrates as additional ingredients, as in a conventional beverage. In addition to the above, the health functional food composition of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin , alcohol, a carbonation agent used in carbonated beverages, and the like. In addition, it may contain the pulp for the production of natural fruit juice, fruit juice beverage and vegetable beverage.

Since the Bojungikgi-tang extract of the present invention, and more specifically, the Bojungikgi-tang water extract is made from natural medicinal plants, even when used as a pharmaceutical composition or food composition, it may have fewer side effects compared to general synthetic compounds, so it can be safely contained and usefully used. have.

Hereinafter, the configuration and effects of the present invention will be described in more detail through examples. These examples are only for illustrating the present invention, and the scope of the present invention is not limited by these examples.

Example 1: Preparation of Experimental Materials and Experimental Methods

Example 1-1: Preparation of Bojungikgi-tang extract

The medicinal crops used in the present invention were purchased from Gwangmyeongdang Pharmaceutical Wholesale (onherb) certified by the Ministry of Food and Drug Safety's good manufacturing practice (GMP) on the basis of the Korean Pharmacopoeia. After washing all medicinal crops individually at the content (wt%) shown in Table 1 below, water 10 times the sample weight (513.1 g) was added, and then using the reflux cooling extraction method at 105 ° C. for 5 hours, twice. Repeatedly, hot water extraction was performed. The extracted sample was concentrated at 55°C using a large rotary vacuum concentrator (Eyela, NVC-2200, ToKyo, Japan), and then filtered using a filter paper (filter paper; Thermo, Waltham, MA, USA). The filtered Bojungikgi-tang extract (BPS) was dried using a freeze dryer.

Components and content ratio (wt%) constituting the Bojungikgi-tang extract ingredient scientific name content (g) weight Astragalus Astragalus membranaceus Bunge 5.62 24.6 Ginseng Panax ginseng C. A. Meyer 3.75 16.4 Baekchul Atractylodis Rhizoma Alba 3.75 16.4 licorice Glycyrrhizae Radix et Rhizoma 3.75 16.4 donkey Angelicae Gigantis Radix 1.875 8,2 dermis Fraxini Cortex 1.875 8.2 riding Cimicifugae Rhizoma 1.12 4.9 Shiho Bupleuri Radix 1.12 4.9 health Zingiber officinale Roscoe page 3 jujube Zizyphi Fructus 2 Sum 22.86 100

163 g of the test material was obtained, confirming a yield of about 31.8%, and the dried powder was dissolved in 0.5% carboxymethyl cellulose (CMC, Sigma, St. Louis, MO, USA) before use.

Example 1-2: Experimental animals and treatment

Male 7-week-old BKS.Cg-m+/Leprdb/+/J and BKS.Cg-m+/Leprdb/db/J mice were purchased from Orient Bio (Jeongeup, Korea), and were divided into 6 groups of 5 mice in each group. Divided into 2 and tested.

group medication number of individuals NOR (normal control) unprocessed 5 CON (Negative Control) sterile tertiary distilled water 5 POS (positive control) 10 mg/kg sitagliptin and
20mg/kg metformin administration 5 BJL 150mg/kg Bojungikgi-tang water extract administration 5 BJM 500mg/kg Bojungikgi-tang water extract administration 5 BJH 1000mg/kg Bojungikgi-tang water extract administration 5

The composition of Bojungikgi-tang used in the animal experiment was referenced in the Dictionary of Oriental Medicine (Kim, 2001), and the ADI (Acceptable Daily Intake) calculation method was used to calculate the allowable daily intake for the concentration of one tablet based on an adult body weight of 70 kg. applied to experiments (Nestmann ER. et.al. , Regulatory Toxicology and Pharmacology , 47(3):232-239, 2007).

The test period was 13 weeks, and the positive control group combined 10 mg/kg sitagliptin and 20 mg/kg metformin with reference to other research results related to type 2 diabetes. During oral administration (Hayes J. et al ., Drug Design, Development and Therapy , 10:2263-2270, 2016). The Bojungikgi-tang water extract administration group was orally administered at a concentration of 150 mg/kg, 500 mg/kg, or 1000 mg/kg, respectively. After the end of the experiment, all experimental animals were euthanized by hyperventilation of _{CO 2} according to the laboratory animal management standards of the Institutional Animal Care and Use Committee (IACUC).

Example 1-3: Blood biochemical analysis

The collected whole blood was centrifuged at 3,000 rpm for 10 minutes, and then serum was collected and used. Blood urea nitrogen (BUN) and creatinine (Creatinine, Crea) were analyzed using a FUJI DRI-CHEM 4000i (Fujifilm, Dokyo, Japan) blood biochemistry analyzer.

Example 1-4: hematoxylin and eosin staining

The excised kidneys were fixed in 10% neutral buffered formalin (NBF) and embedded in paraffin through tissue processing. After the embedding, sections were made with a thickness of 5㎛, and hematoxylin (Dako Mayer' Hematoxylin; Agilent, Santa clara, California, USA) and eosin Y (Eosin Y; Sigma, St. Louis, Missouri, USA) were used. After staining using a light microscope, it was observed.

Example 1-5: Staining with Pipro Serious Red

The excised kidneys were fixed in 10% NBF and embedded in paraffin through tissue processing. After the embedding was completed, sections were prepared with a thickness of 5 μm, and after staining using a Picro sirius red stain kit (Abcam, Cambridge, United kingdom), they were observed under an optical microscope. The degree of fibrosis was expressed as a histogram by measuring the intensity of the dyeing color using the Image J program.

Example 1-6: Statistical processing

Statistical processing was performed using SPSS (Chicago, IL, USA), and the mean value and standard deviation were calculated. After one-way ANOVA was performed to verify the mean difference between the experimental groups, statistical differences were evaluated at the significance level p < 0.05 using the Tukey-Kramer Multiple Comparison Test. verified.

Example 2: Analysis of the effect of Bojungikgi-tang on kidney function indicators in an animal model of type 2 diabetes complications

The db/db mouse is a strain with a mutation in the gene that produces the receptor for leptin, a hormone involved in diet and energy homeostasis, and is commonly used in research on various metabolic diseases related to diabetes. Renal damage such as nephropathy is known to occur (Bruke SJ. et. al., J Diabetes Res., 2017:8503754, 2017; Sharma K. et. al., Am J Physiol Renal Physiol., 284(6) :F1138-1144, 2003). Accordingly, an experiment was conducted to find out what effect Bojungikgi-tang had on the renal function index.

As a result of measuring the Cre concentration, the Cre concentration of the normal control group was 0.4±0.2 mg/dL, and that of the negative control group was 1.4±0.2 mg/dL. The positive control group was 0.5±0.1 mg/dL, which was significantly reduced compared to the negative control group. /dL and 0.6±0.2 mg/dL (FIG. 1(A)).

The BUN concentration was 15.0±5.0 mg/dL in the normal control group and 47.7±8.6 mg/dL in the negative control group. The positive control group was 18.7±7.1 mg/dL, which was decreased compared to the negative control group, and the 100 mg/kg, 500 mg/kg, or 1000 mg/kg Bojungikgi-tang water extract group received 31.3±6.5 mg/dL and 24.7±5.0 mg/dL, respectively. dL and 23.0±5.3 mg/dL (FIG. 2(B)). It was confirmed that BUN and Cre concentrations were normally improved in all groups to which Bojungikgi-tang was administered, thereby improving the renal function deterioration caused by type 2 diabetes.

Example 3: Analysis of the effect of Bojungikgi-tang on kidney tissue damage in an animal model of type 2 diabetes complications

As a result of checking the kidney tissue to measure the kidney tissue damage in each experimental group, compared with the normal control group (NOR), the negative control group (CON) showed loss of brush border (yellow), tissue damage (blue), and glomeruli. Atrophy (black) and glomerular hypertrophy (red) appeared, but damage to kidney tissue was blocked in the positive control group and the experimental group administered with Bojungikgi-tang (FIG. 2).

Example 4: Analysis of the effect of Bojungikgi-tang on renal fibrosis in an animal model of complications of type 2 diabetes

In order to measure renal fibrosis in each experimental group, type 1 and type 3 collagens were stained with a peak of the kidney tissue using picro sirius red staining. It has been reported that the synthesis of type 1 and type 3 collagen is increased when tissue fibrosis progresses. Accordingly, as a result of confirming the collagen in the kidney tissue, the degree of renal fibrosis was severe in the negative control group (CON) compared to the normal control group (NOR), but renal fibrosis was blocked in the positive control group and the experimental group administered with Bojungikgi-tang (Fig. 3).

Summarizing the above series of results, when the Bojungikgi-tang water extract was applied to an animal model of type 2 diabetes complications, the concentrations of blood urea nitrogen and creatinine were reduced (FIG. 1), kidney tissue damage (FIG. 2), and renal fibrosis (FIG. 3), it was found that the Bojungikgi-tang extract can be usefully used to prevent or treat diabetic nephropathy.

Preparation Example 1: Preparation of a pharmaceutical composition for preventing or treating diabetic nephropathy containing Bojungikgi-tang extract as an active ingredient

Preparation Example 1-1: Preparation of powder

1 g of lactose was mixed with 2 g of the Bojungikgi-tang water extract of the present invention, and the powder was prepared by filling in an airtight bag.

Preparation Example 1-2: Preparation of tablets

100 mg of Bojungikgi-tang water extract of the present invention, 100 mg of corn starch, 100 mg of lactose and 2 mg of magnesium stearate were mixed, and then tableted according to a conventional tablet manufacturing method to prepare tablets.

Preparation Example 1-3: Preparation of capsules

100 mg of Bojungikgi-tang water extract of the present invention, 100 mg of corn starch, 100 mg of lactose and 2 mg of magnesium stearate were mixed, and then filled into gelatin capsules according to a conventional capsule preparation method to prepare capsules.

Preparation Example 1-4: Preparation of a ring

After mixing 1 g of the Bojungikgi-tang water extract of the present invention, 1.5 g of lactose, 1 g of glycerin and 0.5 g of xylitol, it was prepared so as to be 4 g per ring according to a conventional method.

Preparation Example 1-5: Preparation of granules

After mixing 150 mg of Bojungikgi-tang water extract of the present invention, 50 mg of soybean extract, 200 mg of glucose and 600 mg of starch, 100 mg of 30% ethanol was added and dried at 60° C. to form granules, and then filled in a bag. .

Preparation Example 2: Preparation of food for preventing or improving diabetic nephropathy containing Bojungikgi-tang extract as an active ingredient

Preparation Example 2-1: Preparation of wheat flour food

0.5 to 5.0 parts by weight of the water extract of Bojungikgi-tang of the present invention was added to wheat flour, and breads, cakes, cookies, crackers and noodles were prepared using this mixture.

Preparation Example 2-2: Preparation of soups and gravies

By adding 0.1 to 5.0 parts by weight of the water extract of Bojungikgi-tang of the present invention to soup and broth, processed meat products for health promotion, soup and broth of noodles were prepared.

Preparation 2-3: Preparation of ground beef

Ground beef for health promotion was prepared by adding 10 parts by weight of the water extract of Bojungikgi-tang of the present invention to ground beef.

Preparation Example 2-4: Preparation of dairy products

5-10 parts by weight of the water extract of Bojungikgi-tang of the present invention was added to milk, and various dairy products such as butter and ice cream were prepared using the milk.

Preparation Example 2-5: Preparation of wire

Brown rice, barley, glutinous rice, and barley radish were pregelatinized by a known method and dried, and then roasted and prepared as a powder having a particle size of 60 mesh with a grinder.

Black soybeans, black sesame, and perilla were also steamed and dried by a known method, and then roasted and prepared into powder having a particle size of 60 mesh with a grinder.

The water extract of Bojungikgi-tang of the present invention was concentrated under reduced pressure in a vacuum concentrator, and the dried product obtained by drying with a spray and hot air dryer was pulverized to a particle size of 60 mesh with a pulverizer to obtain a dry powder.

The grains, seeds and water extract of the present invention were prepared by mixing the above-prepared Bojungikgi-tang in the following ratio:

Grains (30 parts by weight of brown rice, 15 parts by weight of barley radish, 20 parts by weight of barley), seeds (7 parts by weight of perilla, 8 parts by weight of black beans, 7 parts by weight of black sesame), Bojungikgi-tang water extract of the present invention (3 parts by weight) , Reishi (0.5 parts by weight), Rehmannia (0.5 parts by weight).

Preparation Example 2-6: Preparation of health drinks

Instant sterilization is achieved by homogeneously mixing 5 g of Bojungikgi-tang water extract of the present invention with auxiliary materials such as high fructose (0.5%), oligosaccharide (2%), sugar (2%), salt (0.5%), and water (75%). After this, it was prepared by packaging it in a small packaging container such as a glass bottle or a plastic bottle.

Preparation Example 2-7: Preparation of vegetable juice

Vegetable juice was prepared by adding 5 g of the Bojungikgi-tang water extract of the present invention to 1,000 ml of tomato or carrot juice.

Preparation Example 2-8: Preparation of fruit juice

Fruit juice was prepared by adding 1 g of the Bojungikgi-tang water extract of the present invention to 1,000 ml of apple or grape juice.

Claims (5)

A pharmaceutical composition for the prevention or treatment of diabetic nephropathy, comprising a bojungikgi-tang extract consisting of astragalus, ginseng, baekchul, licorice, angelica, dermis, horseback riding, shiho, health and jujube as an active ingredient.
The method of claim 1, wherein the bojungikgi-tang extract is 22 to 26% by weight of astragalus, 15 to 18% by weight of ginseng, 15 to 18% by weight of baekchul, 15 to 18% by weight of licorice, 7 to 9% by weight of angelicasis, 7 to 9% by weight of dermis Weight%, horseback riding 4 to 5.5% by weight, Shiho 4 to 5.5% by weight, health 2 to 4, and a mixed extract of 1 to 3 jujubes, a pharmaceutical composition for preventing or treating diabetic nephropathy.
The pharmaceutical composition for preventing or treating diabetic nephropathy according to claim 1, wherein the extraction solvent of the Bojungikgi-tang extract is water, C ₁ to C _{4 lower alcohol or a mixture thereof.}
A food composition for preventing or improving diabetic nephropathy, comprising, as an active ingredient, a bojungikgi-tang extract consisting of astragalus, ginseng, baekchul, licorice, angelica, dermis, horseback riding, shiho, health and jujube.
According to claim 4, wherein the bojungikgi-tang extract is 22 to 26% by weight of astragalus, 15 to 18% by weight of ginseng, 15 to 18% by weight of baekchul, 15 to 18% by weight of licorice, 7 to 9% by weight of angelicasis, 7 to 9% by weight of dermis Weight%, horse riding 4 to 5.5% by weight, Shiho 4 to 5.5% by weight, health 2 to 4, and a mixed extract of 1 to 3 jujubes, a food composition for preventing or improving diabetic nephropathy.

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