KR20030059951A - Composition containing an extract of sopungsungi-won crude drug complex for preventing and treating diabetes mellitus - Google Patents

Abstract

PURPOSE: A composition containing as an effective ingredient Sopungsungiwon(prescribed according to the representative oriental medical publications of "Dong-I Bogam") is provided. The composition reduces blood sugar, neutral lipid in blood and free fatty acid, inhibits the release of albumin and sugar and recovers a pancreatic β-cell function. Therefore, it can be used as a drug and a health supplementary food for prevention and treatment of diabetes and complications associated with diabetes. CONSTITUTION: A pharmaceutical composition contains 0.5 to 50% by weight of Sopungsungiwon(prescribed according to the representative oriental medical publications of "Dong-I Bogam") and a pharmaceutically acceptable carrier, based on the total weight of the composition. To prepare Sopungsungiwon, Rhei Rhizoma is mixed with a mixture of Plantago asiatica L., Prunus japonica Thunb., Areca catechu L., Cannabis sativa L., Cuscuta japonica Choisy., Achyranthes japonica Nakai, Dioscorea batatas Decne. and Cornus officinalis Sieb. et Zucc. and a mixture of Poncirus trifoliata Rafin., Ledebouriella seseloides and Aralia cordata Thunb. in a weight ratio of about 1 to 10:1 to 5:1 and then extracted. The complications associated with diabetes are caused by increase of neutral lipid, cholesterol and high-density lipid.

Description

COMPOSITION CONTAINING AN EXTRACT OF SOPUNGSUNGI-WON CRUDE DRUG COMPLEX FOR PREVENTING AND TREATING DIABETES MELLITUS}

It is an object of the present invention to provide a pharmaceutical composition and dietary supplement showing the effect of preventing and treating diabetes and its complications.

The present invention relates to a composition for the prevention and treatment of diabetes, including extracts from the excipient net origin herbal medicines.

Type 2 diabetes, also known as insulin-independent diabetes, is a disease that occurs in middle-aged adults, and in Western society, about 2 to 6% of adults suffer from this disease. Insufficiency of insulin secretion due to insulin resistance and disrupted pancreas leads to metabolic diseases causing hyperglycemia. It is reported that such diabetes can inhibit the onset and progression of diabetic disease through thorough urine glucose control and control (Diabetes Controlled Clinical Research Association, N. Eng. J. Med., 329 , p977-986, 1993). Hyperglycemia can also be caused by various pathologies such as hyperosmolarity, oxidant formation, abnormal metabolism of sorbitol and myoinositol, and activation of diacylglycerol (DAG) -protein kinase C (PKC). It has been reported in Brownlee et al . (Brownlee et al: J. Engl. J. Med. 318 , p1315-1321, 1998), and diabetic nephropathy is a late stage. Renal disease (ESRF) is a typical etiology and the early stages of diabetic nephropathy are characterized by glomerular epilepsy, accumulation of extracellular matrix, and increased urinary albumin excretion. Obvious nephropathy clinically causes proteinuria, hypertension and progressive renal failure.

High levels of blood glucose pose a risk to nonenzymatic and enzymatic mechanisms, including major signal transduction processes and regulation of hypertrophic and prefibrous cytokine transforming growth factors (TGF-β), according to Sharma et al. Sharma K and Ziyadeh FN: Semin.Neprol. 17 , p 80-92, 1997). Concerning the cellular signaling process, high concentrations of glucose increase DAG neosynthesis with PKC activation, according to Craven PA and De Rubertis FR: J. Cln. Invest. 83 , p1667. -1675, 1989), the activation of PKC is an important intracellular mediator of diabetic complications, and the use of nonspecific and specific inhibitors for PKC isozyme has been shown to result in high concentrations in in vitro and in vivo tests of diabetic kidney disease. Inhibiting the transformation of glucose-induced cellular function has been reported in Studer et al. (Studer RK, et al: Diabetes 42 , p118-126, 1993).

More recently, extracellular signal-regulated kinase-1 / 2 (ERK 1/2 or p42 / 44 MAPK), stress-activated C-Jun N-amino terminal kinase (JNK / Stress-activated protein kinase or SAPK) and p38 Three groups of mitogen-activated protein kinases (MAPKs), such as MAPK, have been identified and isolated, and these enzymes can be activated by a variety of external stimuli, including growth factors and environmental stresses. It has been reported in Segar et al. (Segar R and Krebs EG: FASEB J. Jun, 9 (9) , p726-35, 1995), which plays a key role in the signaling system that drives transformation.

In relation to diabetes, ERK is known to be activated not only in glomerular stromal cells cultured in hyperglycemic state but also in glomeruli of diabetic rats, and ERK activation in these cells is generated through PKC-dependent mechanisms (Haneda et al. Haneda M et al: Diabetes 46 (5) p847-53, 1997), Igarashi et al. , Igarashi M et al. , Found that P38 MAPK is activated by relatively high blood sugar levels in various cells, including glomerular interstitial cells. et al: J. Clin. Invest. 103 (2) p185-95, 1999). In contrast to these two kinases, JNK is not activated in the glomeruli of diabetic rats, Since it is not stimulated, the ERK activation process may be involved in intracellular signaling systems that cause cellular dysfunction in diabetes mellitus, for example ERK is a three-dimensional complex One of them is Janknecht, R et al: EMBO J , which activates Elk-1 and induces c-fos transcription to induce subsequent production of activator protein-1 (AP-1) transfer factor complexes. . Dec (15), it has been reported in 12 (13), p5097-104, 1993 ).

In order to examine the mechanism of drug efficacy, the pancreas, insulin-dependent tissues (muscles, fat, liver, etc.), small intestine, kidneys, etc. were extracted from the experimental animals to check the targets of the cause of diabetes one by one, and then insulin secretion and glucose into the tissues. The effects on influx, carbohydrate metabolism or uptake can be identified using biochemical and molecular biological techniques at the tissue or cellular level.

Various types of conventional diabetes treatments have a function of inhibiting hyperglycemia to some extent, but many patients with type 2 diabetes have difficulty controlling blood sugar and are known to progress to serious complications. Common uses for the treatment of diabetes include oral hypoglycemic agents and insulin administration.

The present invention was to search for a natural herbal complex composition effective for such diabetes.

Excursion Soon Ki-won (疏風 順 氣 元) is stated in Huh Jun's consent and use as a laxative to soften the stool, mainly in the elderly (see agreement, Huh Jun, stool in the inner diameter), the composition of the prescription is rhubarb, Document of the secondary electron, Wook Reinforced, betel, etc. as soon as the, tosaja, wooseul, Yam, Cornus officinalis, jisil, wind, consists of 12 herbal of Aralia cordata, jeongboseop (jeongboseop, sinmingyo low, hyangyak Dictionary, Younglim Inc., 1998 According to)

Rhubarb refers to the roots of Rheum undulatum L., R. officinale B., R. coreanum Nakai, and R. palmatum L. , Antibacterial effect, anti-tumor effect, etc., and its components are known as anthraquinone derivatives such as emodin (emodin), aloe emodin (aloeemodin) (p327-328),

Chason refers to seeds of Plantago asiatica D., P. camtschatica C., P. depressa W. and P. japonica F. It is known to have a therapeutic effect on diuresis, arthritis, etc., and its components are known as aucubin, plantaginin, and ursolic acid (p1004-1006). ,

As a seed of Prunus japonica Thunb var Nakai, P. triloba var truncata Kom, P. tomentosa Thunb, and P. ishidoyana Nakai , Constipation treatment, and its components are known components such as amygdalin (amygdalin), fatty oil, oleic acid (p627-628),

Betel nut is a seed of betel nut ( Areca catechu L.), and its insecticidal effect is known, and its ingredients are known as alkaloids such as arecoline, guvacine and arecolidine. ,

Mazarin (麻子 仁) is a seed of hemp ( Cannabis sativa L.), and it is known to treat constipation, and its components include fatty oil, oleic acid, and linolenic acid (p548-550).

Earthworms are the seeds of Cuscuta japonica Choisy, C. australis R. and C. chinensis Lam, which are known as potents and tonics, and include resin glycosides and vitamin A. Components are known (p882-883),

Root is the root of Achyranthus japonica Nakai and A. bidentata Bl. It is known to have diuretic and analgesic effects. Its components include ecdysone and ecdys Components such as ecdysterone and triterpenoid saponin are known (p340-341),

The mountain medicine is a tuber of hemp ( Dioscaa batatas Decne) and Yam ( D. japonica Thunb), and it is known as a tonic and tonic tablet, and its components include saponin, cholie, starch, and apsisin. Abscisin) are known (p147-149),

Cornus of the Cornus officinalis Sieb is used as a tonic and tonic, and its constituents include cornin, tannin and vitamin A (p448-449).

Fruits are young fruits of Citrus aurantium L., and are known for their effects on gastrointestinal diseases and uterine contractions. Flavonoid glycosides and vitamin C are known as ingredients (p779-). 780),

Windproof (防風) is the root of Windproof ( Ledebouriella seseloides Wolf.) And Root Sprouts ( Pusedanum japonicum Thunb), known for its antipyretic and analgesic effects. (p428-429),

Toxic activity uses the root and muscle of Aralia cordata Thunb, and is known to be effective in sweating, fever, diuresis, and pain, and its components include limonene and sabinene. Essential oil components such as these are known (p435-436).

However, there have been no reports of the therapeutic effect of diabetes mellitus, which is a combination of the herbal medicines, until now.

The inventors of the present invention, extracts of complex herbal medicine consisting of rhubarb, charcoal, charcoal, urine, betel nut, mother's fruit, earth and sand, hyssop, powder, cornus, fruit and vegetable, windproof, poisonous, have a therapeutic effect on diabetes and its complications. Discover the excellence and complete the present invention.

It is an object of the present invention to provide a pharmaceutical composition and dietary supplement showing the effect of preventing and treating diabetes and its complications.

1 is a graph showing the weight change of ZDF rats to which the excipient net origin complex of the present invention was administered, the mean ± SE of each value. (○) is the control group, (▲) is the sample (200 mg / kg) Treatment group, (■) sample (500 mg / kg) treatment group, (●) indicates the control drug logiglitazone (10 μmol / kg) treatment group. Compared with the control group, P value is 0.05 or less, * 0.01 or less, ** and 0.001 or less are marked with ***.

Figure 2 is a test of the effect of the sample and the control drug on the blood glucose of the ZDF rat, the meaning of (○), (▲), (■), (●) and the significance sign is the same as the meaning in FIG.

Figure 3 is a test of the effect of the sample group and the control drug on the blood glycated hemoglobin (HbA1c) in ZDF mice, the meaning of (○), (▲), (■), (●) and significance indicator is shown in Figure 1 Same as meaning.

Figure 4 is a diagram showing the insulin level in the blood at 0 to 8 weeks of treatment of the sample and the control, the circle represents the insulin value of each individual, the line represents the mean of each group. C represents a ZDF control, SP2 is a sample (200 mg / kg) treatment group, SP5 is a sample (500 mg / kg) treatment group, RSG is a control drug treatment group. The meaning of the significance indication is the same as the meaning in FIG.

5 is a 100-fold magnification of staining with hematoxylin and eosin in pancreas of ZDF rats treated with a sample and a control drug, 5A is a control rat, 5B is a sample (200 mg / kg) treated rat, 5C is a sample (500 mg / kg) treated rat, 5D is a control drug treated rat.

6 is a 100-fold magnification of immunostaining with insulin antibodies in pancreas of ZDF rats treated with a sample and a reference drug, 5A is a control rat, 5B is a sample (200 mg / kg) treated rat, 5C is Sample (500 mg / kg) treated rats, 5D, were control drug treated rats.

7 is a diagram showing the effect on urinary glucose excretion by treatment of the sample and the control drug for 0, 4 and 8 weeks, (□) ZDF control; (*), 200 mg / kg sample treatment group; (■), 500 mg / kg sample treatment group; (Iii), the control drug treatment group and the meaning of the significance label is the same as the meaning in FIG.

FIG. 8 is a diagram showing the effect on urinary albumin secretion by treatment of samples and control drugs for 0, 4 and 8 weeks, and the meanings of (□), (▒), (■), and (▨) are shown in FIG. 7 and FIG. The meaning of the significance indication is the same as that in FIG.

9 is a diagram showing the effect on the concentration of triglycerides in the blood of the sample and the reference drug, and the meaning of (○), (▲), (■), (●) and significance mark is the same as the meaning in FIG. .

10 is a view showing the effect on the concentration of free fatty acids in the blood of the sample and the control, the meaning of (○), (▲), (■), (●) and significance is the same as the meaning in FIG.

In accordance with the above object, the present invention is a picnic pure source, ie rhubarb, chacha, wooryin, betel nut, mazain, earthenware, dew, powder, cornus, fruit juice, windproof, poisonous extract including diabetes prevention and treatment thereof It is to provide a composition for.

The composition for treating diabetes mellitus of the present invention comprises 0.5-50% by weight of the extract of excipient net origin based on the total weight of the composition.

Each herbal medicine of the present invention includes all the herbal medicines derived from the same plant, but the composition ratio of the individual compositions is not limited in the present invention, but preferably, rhubarb and tea, urine, betel, mazain, earth and sand, and dew The weight composition ratio of the three herbal medicines such as medicinal herbs, eight herbal medicines of cornus oil, lychee, windproof and poisonous bowel is about 1 to 10: 1 to 5: 1, more preferably about 3 to 7: 2 to 4: 1, even more preferred. For example, the composition ratio is about 5: 2.5: 1.

The combined herbal extracts of the present invention are all dried and then crushed in the case of seeds, chopped in the case of root or rhizome, and then water of about 1 to 15 times, preferably about 5 to 10 times the volume of the herbal medicine, Lower alcohol or a mixed solvent having a mixing ratio of about 1: 0.1 to 1:10, preferably 1: 1 to 1: 3, at a extraction temperature of 20 to 100 ° C, preferably 70 to 100 ° C, for about 1 hour to It can be obtained by extraction methods such as ultrasonic extraction, reflux extraction and the like on 2 days, preferably about 2 hours to 1 day.

The present invention provides a composition for the prevention and treatment of diabetes mellitus and its complications, including the water extract obtained in the extraction process, the lower alcohol extract, and soluble extracts according to a mixed solvent thereof.

The composition comprising the complex herbal extract of the present invention may further comprise a suitable carrier, excipient and diluent according to conventional methods.

Carriers, excipients and diluents that may be included in the composition comprising the complex herbal extract of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin , Calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

The composition comprising the herbal extract extract according to the present invention is in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories, and sterile injectable solutions, respectively, according to a conventional method. Can be formulated and used.

The amount of the combined herbal extract of the present invention may vary depending on the age, sex, and weight of the patient, but may be administered once to several times daily in an amount of 0.1 to 500 mg / kg. In addition, the dosage of the extract can be increased or decreased depending on the route of administration, the degree of disease, sex, weight, age and the like. Therefore, the above dosage does not limit the scope of the present invention in any aspect.

The composition comprising the complex herbal extract of the present invention may be used in various forms such as pharmaceuticals, foods and beverages for the prevention and treatment of diabetes and its complications. Examples of the food to which the herbal extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health supplements.

The herbal extracts of the present invention are medicaments that can be used with confidence even when taken for long periods of time, as they have little toxicity and side effects.

The complex herbal extract of the present invention may be added to food or beverage for the purpose of preventing diabetes and its complications. At this time, the amount of the complex herbal extract in the food or beverage is generally added to the health food composition of the present invention 0.1 to 15% by weight, preferably 1 to 10% by weight of the total food weight, the food health beverage composition is It can be added at a ratio of 1 to 30 g, preferably 3 to 10 g based on 100 m1.

The health beverage composition of the present invention is not particularly limited in the liquid component except for containing the extract as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates, etc. as additional ingredients, as in general beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.), and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The ratio of said natural carbohydrate is generally about 1-20 g, preferably about 5-12 g per 100 m1 of the composition of the present invention.

In addition to the above, the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and salts thereof. , Organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. The compositions of the present invention may also contain pulp for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

As a result of the preliminary experiments, the composition of the present invention has been observed that the excipient net source of blood sugar lowering action and triglyceride reduction effect is excellent. Based on this, the two-dose excipient net extracts were administered in a dry powder state for 8 weeks, using a Zucker Diabetic Fatty rat. The dose-dependent hypoglycemic activity and triglyceride And it was confirmed that the cholesterol reducing activity is excellent.

The present invention is described in more detail based on the following examples, although the present invention is not limited thereto.

Example 1 Preparation of Extracts of Picnic Soon Gi Won Medicinal Herbs

937.5g of dried rhubarb purchased from Yeongdong Market in Gyeongdong Market, tea, urinary, fruit, mazain, earthenware, hyssop, acid and corn, 375g each, Jisil, windproof, poisonous water 187.5g each Was added and the extract obtained by heating under reflux at a temperature of 80-100 ° C. for 2 hours was lyophilized with a lyophilizer (FN-5N, EYELA, Japan) to use 120 g of an excipient net source complex herbal dried product as a sample ( Yield: 8.31%).

Reference Example 1. Preparation and Pretreatment of Experimental Materials

Laboratory Animals and Comparative Drugs

Male ZDF (Zucker Diabetic Fatty) rats used in this experiment were analyzed by Genetic Models Ins. (Indianapolis, IN, USA). Rosiglitazone used as a comparative drug was supplied from Glaxo-SmithKline.

Blood index analysis method

Blood glucose levels were measured weekly using a TRinder solution (Sigma Diagnostics, USA) using the glucose oxidase method. Blood glycated hemoglobin concentration was measured using glycated hemoglobin HbA1 kit (Sigma) by cation exchange method in blood collected from rats reared for 8 weeks. Blood insulin levels were measured at 415 nm using a kit by insulin radioimmunoassay in blood prior to and 8 weeks of administration. Blood triglyceride levels were measured using the GPO-Trinder kit (Sigma) and free fatty acid concentrations were measured using the NFAZYME-S kit using the acyl-CoA oxidase method. AST and ALT were also analyzed in each kit, and urinary albumin excretion was measured using an albumin solution (Yongdong Pharm., Korea).

Statistical processing method

All experimental results were expressed as mean ± SE, and statistical processing was performed by the Student t-test to determine the significance based on P <0.05.

Experimental Example 1: Weight change and hematuria index change experiment

Seven-week-old ZDF rats were purchased and acclimated to the laboratory for one week, and then the samples were administered to the eight-week-old ZDF for eight weeks. The experimental animals were bred in a kennel maintained at a humidity of 50% and a temperature of 24 ~ 26 ℃, and water was supplied for free intake. Seven groups of blood glucose and body weight were divided into four groups before the administration of the sample as follows: The control group was supplied with a rat rat general feed (Samyangsa, Korea), and the picnic group received two doses per kg body weight. The excipient was fed to feed so that 200 mg or 500 mg intake. In addition, the comparative drug group was supplied with rosiglitzone mixed with feed so that the intake amount per kg body weight was 10 μM. Sample dose was determined by examining the dietary amount for 3 days before starting the administration, and the sample volume was changed every two weeks according to the weight and diet.

Changes in body weight were measured weekly, and blood obtained by orbital blood collection with heparinized capillaries was centrifuged to store plasma at -20 ° C. From this, glucose, triglyceride, and free fatty acid concentrations were measured. Blood collection was performed at 3 pm. After anesthesia, blood was collected through the orbital vein and centrifuged at 5,000 rpm for 10 minutes to use the obtained plasma. For urinary index analysis, rats were transferred to metabolic cages and urine collected for 24 hours to measure glucose and albumin excretion in urine collected before and after 4 and 8 weeks of administration of samples and controls. In the blood obtained at the last week of administration, the concentrations of glycated hemoglobin, insulin, cholesterol, HDL, ALT, and AST were measured.

Results of dietary and water intake and weight change among groups

In the case of dietary intake, the control group and the excursion While there was no difference between the administration group (SP2: 200 mg / kg treated sample, SP5: 500 mg / kg treated sample), the control group, the rosiglitazone-treated group, was significantly reduced compared to the control group. For 8 weeks, the weight gain of the control group increased by 135 g, while the SP2 increased by 186 g, SP5 by 185 g, and the control by 332 g. When the dietary efficiency (weight gain divided by total dietary intake) was calculated and the control group was 100%, SP2 was 143%, SP5 was 137%, and the control group was 294%. As shown in FIG. 1, the control group showed a tendency to decrease slightly rather than increasing weight from 6 weeks (14 weeks after birth), whereas the sample administration group showed a tendency to increase gradually little by little. Compared with the control group, the sample-administered group showed no difference in dietary intake, but the weight increased compared to the control group. Regardless of the sample dose, the dietary efficiency was 37-43% higher than the control group. In contrast, the control group showed a significant increase in body weight compared to the amount eaten at 294%. From the 4th week of control drug administration, body weight was significantly increased compared to the control group. On the other hand, when comparing the water intake between the groups, as shown in Table I, compared with the control group showed a reduction rate of 40%, 44%, 55% in the order of SP2, SP5, control drug administration group, respectively. The dose group reduced water intake in a dose-dependent manner, suggesting that there was activity to improve diabetic symptoms. Feed and water intake were examined at the last week of treatment and data were mean ± SE compared to control. *P<0.05, **P<0.01, ***P<0.001.

Control sample Reference drug 200 mg / kg 500 mg / kg 10 μM / kg Dietary Amount (g / rat / day) 33.0 ± 0.7 33.4 ± 0.7 33.5 ± 1.3 35.4 ± 0.8 * Drinking water amount (ml / rat / day) 111.0 ± 3.5 70.3 ± 3.8 ^*** 62.7 ± 4.0 ^*** 63.2 ± 1.2 ^***

Comparison of Geological Changes Between Groups

Table 2 shows the results of examining the effect on blood lipids of each sample. As shown in Table 2, the sample-administered group showed the activity of improving total cholesterol, HDL, and triglyceride levels at the 500 mg / kg dose, while the control group did not affect the total cholesterol or HDL, while it significantly lowered triglycerides. Indicated. Compared with the control group, 51% of SP5 group and 84% of control group showed triglyceride-reducing activity. In the case of the control drug or the sample administration group in Figure 1, while the weight is steadily increased, triglyceride in the blood shows a low inverse correlation. These samples are thought to have an effect of lowering triglycerides by affecting the absorption, metabolism or excretion of triglycerides. Data are expressed as mean ± SE and show * P <0.05, ** P <0.01 *** P <0.001 compared to control.

Control sample Reference drug 200 mg / kg 500 mg / kg 10 μmol / kg Triglyceride concentration (mg / dL) 650 ± 70 658 ± 50 319 ± 34 ^*** 107 ± 8 ^*** Free Fatty Acid Concentration (mEq / L) 1.69 ± 0.05 1.56 ± 0.06 1.07 ± 0.07 ^*** 0.39 ± 0.08 ^*** Total Cholesterol (mg / dL) 134.5 ± 4.1 123.9 ± 3.5 ^* 107.7 ± 4.3 ^*** 137.3 ± 14.1 HDL (% of total cholesterol) 22.0 ± 1.2 20.0 ± 1.4 26.6 ± 1.6 * 19.0 ± 1.5

Comparison of blood glucose, blood insulin and glycated hemoglobin changes among groups

Figure 2 is the result of observing the change in blood glucose during 8 weeks of sample administration. In all samples, the blood glucose increase was suppressed from 1 week of administration compared with the control group. Especially, SP5 and the control group showed distinct blood glucose increase inhibitory activity with almost no blood glucose increase during 8 weeks. In the pre-administration period, the SP2 and SP5 groups showed differences in blood glucose levels up to 3 weeks after administration, but no significant difference was found between the two doses after 4 weeks of administration. At 15 weeks of age (the last week of administration), the blood glucose level of the ZDF control group was 404 mg / dl, whereas the SP2, SP5, and control groups were 162, 116, and 107 mg / dl, respectively. Zucker lean fa / + or + / +, the same age) blood sugar level of 90 mg / dl was almost the same level of activity.

Figure 3 is a result of comparing the glycated hemoglobin in blood between groups. Glycated hemoglobin is a measure of long-term changes in blood glucose, which is 4-6% normal. As shown in FIG. 3, the ZDF control group showed an average glycated hemoglobin level of 6.85%, which was higher than that of the normal group, while the sample administration group was 6.26%, 5.64%, and 5.25%, respectively, in the order of SP2, SP5, and control drug. This result is in agreement with the result of the blood glucose raising inhibitory activity of the sample of FIG. In the case of SP5 administration group, the glycated hemoglobin level was decreased by 1.21% compared with the control group. When the sample is administered for 8 weeks and the glycated hemoglobin level is decreased by more than 1%, it is usual to determine that the blood glucose lowering activity of the sample is clear, and thus the result indicates that the sample is steadily controlling blood glucose. Although the control group showed the highest activity in the sample by reducing the glycated hemoglobin by 1.6%, the RSG dose used in this experiment was likely to cause liver toxicity. While showing a similar size to the activity, the toxicity was found to be less advantage.

As shown in Figure 4, parallel with the induction of hyperglycemia of ZDF control rats showed a marked lowering effect of plasma insulin concentration of 26.1 μU / ㎖ in 7-week-old mice, 14.8 μU / ㎖ in 15-week old mice. However, the blood insulin concentration did not decrease in the sample treatment group, whereas the SP5 group (31.9 μU / ml) showed a significant increase in insulin compared to the ZDF control rat (14.8 μU / ml).

Urinary Glucose and Protein Excretion Between Groups

As shown in FIG. 7, more than 3.3 g of glucose per day is typically excreted in the urine as hyperglycemic symptoms progress in ZDF control rats. On the other hand, in the sample treatment group, diabetes mellitus was reduced in dose-dependent manner, and the control group was hardly detected.

As diabetes mellitus progresses, ZDF control rats develop kidney glomerular defects. As shown in FIG. 8, proteinuria begins to occur from the first month of the test, and at 2 months, the ZDF control secretes 64.2 mg of protein per day. Samples were found to inhibit urinary albumin secretion after 4 weeks of treatment and to reduce albumin secretion by 29% (SP2) and 44% (SP5), respectively, at the end of treatment.

Changes in Serum Lipid Levels between Groups

There is a significant correlation between obesity and dyslipidemia, and normalization of lipid dyslipidemia in blood is normal because insulin levels in circulating free fatty acids and triglycerides are associated with progression of insulin resistance in muscle and adipose tissue. Is expected to improve insulin sensitivity. Therefore, as a result of examining the effects on blood triglyceride and free fatty acid levels of the sample administration group and the control drug group once a week, as shown in Figure 9 maintained at 500 to 800 mg / dL level in the ZDF control and sample treatment group SP2 However, triglyceride levels decreased after 1 week of treatment in the SP5 group. At the end of the treatment, SP5 reduced triglycerides by 51% compared to the ZDF control rats.

In addition, the free fatty acid level was 1.5-2.5 mEq / L during the experimental period in the ZDF control rats and SP2 treated rats, as shown in FIG. 10, but the free fatty acid level was significantly higher in the SP5 and control drug treated groups from 2 weeks of treatment. Decreased.

Experimental Example 2: Experiment of Morphological Changes of the Pancreas

To examine the morphological changes of the ZDF pancreas after 8 weeks of sample treatment, anesthesia was performed with urethane (0.9 ml / 100 g body weight), and then the pancreas was taken and fixed in 4% formaldehyde solution overnight, and the adipose tissue was removed. Fixed. Tightly fixed pancreas tissue was finely cut to remove paraffin and stained with hematoxylin and eosin.

As a result, in parallel with the progression of hyperglycemia in the ZDF control rats, as shown in FIG. 5A, the destruction of pancreatic islet cells of the ZDF control rats was observed and morphological changes were observed. In FIGS. 5B and 5C, As shown in the blood insulin data, SP2-treated mice showed less progression of islet cell destruction than the control group, and SP5-treated mice showed that the islet cells remained intact.

Experimental Example 3: Immune Tissue Staining with Insulin Antibody

0.1 M phosphate buffer (pH 7.4) was flowed through the heart of the anesthetized rat to remove blood and perfused 4% paraformaldehyde. The pancreas was taken and fixed overnight with the same fixative, infiltrated with paraffin to solidify, cut to 7 μm thick with a microtome (802 microtom, American Optical, USA), and then attached to a gelatin-coated slide. Paraffin was removed from the tissue sections and heated in 0.01 M / L citrate buffer (pH 6.0) for 10 minutes. Pancreatic tissue sections were reacted with monoclonal antibodies against insulin (Neomarker, Insulin) and then reacted for 1.5 hours with biotinylated secondary antibody (US Vector). After washing, the peroxidase was reacted with 0.02% DAB (3, 3'-diaminobenzidine tetrachloride) containing 0.01% hydrogen peroxide for about 3 minutes and the slides were observed.

As a result, depletion of the amount of pancreatic insulin in the treated rats (FIGS. 6B, C, D) was not observed as compared with the ZDF control rats (FIG. 6A). Consistent with the experimental results, it was confirmed that β-cell destruction was suppressed in a dose-dependent manner.

Hereinafter, the preparation example of the pharmaceutical composition will be described, but the present invention is not intended to be limited thereto, but is intended to be described in detail.

Formulation Example 1 Preparation of Powder

According to the preparation method of powder in the pharmacopeia formulation, it is prepared in the following ingredient content per one packet.

Example 1 Dried Powder 300 mg

Lactose · ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ 100 mg

Talc 10 mg

Formulation Example 2 Preparation of Tablet

According to the preparation method of tablets in the pharmacopeia formulation, it is prepared in the following component content per tablet.

Example 1 Dry Powders 300 mg

Corn starch ㆍ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ 100 mg

Lactose · ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ 100 mg

Magnesium Stearate 2 mg

Formulation Example 3 Preparation of Capsule

According to the preparation method of capsules in the pharmacopeia formulation, it is prepared in the following component content per capsule.

Example 1 Dry Powder 300 mg

Corn starch ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ 100 mg

Lactose ····················· 100 mg

Magnesium stearate 2 mg

Formulation Example 4 Preparation of Injection

According to the preparation method of injection in the pharmacopeia formulation, it is prepared in the following component content per ampoules (2 ml).

Example 1 Dry Powder 300 mg

Sterile distilled water for injection ㆍ ·············

pH regulator ㆍ ··················

Formulation Example 5 Preparation of Liquid

According to the preparation method of the liquid formulation in the Pharmacopoeia General Formulation, it is prepared in the following component content per 100 ml of the liquid formulation.

Example 1 Dry Powder... 1 g

Heterosaccharides ················· 10 g

Mannitol ···················· 5 g

Purified water ㆍ ···················

In addition, the health beverage is prepared as follows.

5-10% of sugar, 0.05-0.3% citric acid, 0.005-0.02% caramel, 0.1-1% of vitamin C are mixed, and 79-94% of purified water is mixed to make syrup, and the syrup is 85-98 ° C. Sterilized at 20 ~ 180 seconds in a mixture of cooling water and a ratio of 1: 4, and then prepared a carbonated beverage containing an excursion net source dry water extract by injecting carbon dioxide gas 0.5 ~ 0.82%.

Instant sterilization by homogeneously mixing the minor ingredients such as liquid fructose (0.5%), oligosaccharide (2%), sugar (2%), salt (0.5%), water (75%) and tasteless dry extract , Packed in a small packaging container such as plastic bottles to prepare a healthy beverage.

Although the composition ratio is a composition suitable for a preferred beverage in a preferred embodiment, the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and use purpose.

The composition comprising the extract of Pung Soon Ki Won inhibits the rise in blood sugar caused by diabetes and suppresses the excretion of albumin and glucose due to diabetes, the functional recovery effect of pancreatic beta cells, and elevated levels of total cholesterol, triglycerides and free fatty acids. Since it has a lowering activity and shows the prevention and treatment effect of diabetes mellitus and its complications, it can be usefully used as a preventive and therapeutic agent for diabetes.

Claims (8)

Diabetes and tooth made by extract of rhubarb, charcoal, urine, betel nut, mazain, earthenware, hyssop, powder, cornus, fruit, wind, poisonous compound herbal medicines as an active ingredient and mixed with conventional pharmaceutically acceptable carrier Pharmaceutical compositions for the treatment of complications caused. The method of claim 1, Complications caused by diabetes are diseases caused by excretion of albumin, dysfunction of pancreatic beta cells, elevated blood levels of triglycerides, cholesterol, and low density lipids. The method of claim 1, Composition comprising 0.5 to 50% by weight of the composite herbal extract based on the total weight of the composition. The method of claim 1, Composition with weight ratios of rhubarb, tea, Uri-ri, betel nut, mazain, earth and sand, hyaluronic acid, eight herbal medicines of wild corn, and wild fruit, windproof and poisonous herbal medicines of about 1 to 10: 1 to 5: 1 . The method of claim 3, wherein Composition with weight composition of rhubarb, tea, Uri-ri, betel nut, mazain, earthenware, hyssop, 8 herbs of wild corn, wild corn, and fruit, windproof, poisonous herbal of about 3-7: 2-4: 1 The method of claim 4, wherein The composition of rhubarb and tea, Uri-ri, betel nut, mazain, earthenware, hyssop, eight herbs of wild corn and wild corn, and three wild herbs of Jisil, windproof and poisonous are about 5: 2.5: 1. The method of claim 1, A pharmaceutical composition for treating diabetes, wherein the pharmaceutical form is pharmaceutically selected from powders, granules, tablets, capsules, liquids, and injections. Contains extracts of rhubarb, charcoal, urine, betel nut, mazain, earthenware, hyssop, powder, cornus, fruit juice, windproof, poisonous compound, and food-acceptable food additives Health supplement food.