TW200927158A - A medicament composition capable of lowering blood lipid, anti-high uric acid, and anti-diabetes - Google Patents

Abstract

A medicament composition capable of lowering blood lipid, anti-high uric acid, and anti-diabetes, which comprises the extract of the Cordia dichotoma leaf and the medically-acceptable carrier; the extract of the Cordia dichotoma leaf is extracted by using water as the extracting solvent in the ratio of leaf to solvent from 10:1 to 1:10 (weight volume ratio, w/v) under 30 DEG C to 121 DEG C for 30 minutes to 5 hours, and then followed by separation of the leaf residue to obtain the extract solution of the Cordia dichotoma leaf. The extract solution of the Cordia dichotoma leaf can be further concentrated or dried, or without carrying out concentration or drying, and then combined with the medically-acceptable carrier to be made into various types of preparations.

Description

200927158 IX. DESCRIPTION OF THE INVENTION: TECHNICAL FIELD The present invention relates to a pharmaceutical composition for reducing blood fat, anti-hyperuric acid and anti-diabetes, in particular to a water extract containing a leaf of Forst f. Medical composition. [Prior Art] In recent years, due to stable economic development and affluent life, the dietary habits of Chinese people have changed from coarse tea to high-oil and high-calorie exquisite cuisine. Together with the convenience of life, the amount of activity is no longer the same as in the traditional agricultural society. With it, it is the bloody disease, blood lipids, diabetes, cancer, gout and other civilized diseases. § Stomach horse dyslipidemia refers to an increase in blood cholesterol (TC) or tnacylglycerol (TG) than normal. In 1996, the Department of Health of the Executive Yuan of China set the classification criteria for dyslipidemia in Chinese, and classified dyslipidemia into three categories: hypercholesterolemia (hypercholesterolemia), TC concentration greater than 200 mg/dL, and high-density lipoprotein cholesterol-free yeast (high- The concentration of density-lipoprctein-cholesterol, HDL-C) is less than 35 mg/dL, or the concentration ratio of TC/HDL-C is greater than 5; (2) hypertriglyceridemia: TG concentration is greater than 2〇〇mg/ dL; (3) mixed type (4) xedtype): TC and TG concentrations are greater than 2〇〇mg/dL °. Facial dyslipidemia is a common disease--the cause of Gu Da is due to abnormal fat metabolism. In the middle-aged people, the common diseases that are mainly caused are atherosclerosis (4) art cl_is) and cardiovascular disease (嶋卿如如. dyslipidemia, regardless of 200927158 疋 胆 _ 、 、 、 、 、 、 、 、 、 、 Symptoms or mixed type, are the main cause of atherosclerosis, will increase the risk of coronary heart disease, the gallbladder _ value is too high, usually does not appear obvious symptoms, reported many people often neglect, blood in the turn If the long-term is too high, you can On the inner wall of the blood s, these blood vessels become narrow or even slender, resulting in myocardial infarction «Don'· _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Health Statistics Information Network of the Hospital Health Department.): The disease of canned disease and cerebral blood is the second and second of the main deaths of the Nana in Taiwan. First place. General people, Huang Shi, δ, Qian Xin, Yang Huiting, Liu and Xie Mingzhe, genus, daring _ diet added

The total cholesterol in the blood should be low as mg/dL, but there is a small amount of money between the people. Although it is not necessary to make (four) substances to regulate blood lipids, it must be strictly controlled and often exercise to reduce its concentration. It is more ideal to ride the _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Diabetes is a disease in which the body's metabolism is impaired; * The pancreas in the human body cannot produce enough silk fibroin', causing (4) sugar not to fully enter the cells, and blood bribes will rise to form diabetes. Diabetes can be divided into two types: _ is insulin-dependent diabetes mellitus (ID), also known as type-type diabetes, formerly known as juvenile-type diabetes; due to congenital constitution and acquired detoxification or chemical miscellaneous At the time of the job, the beta cells of insulin were destroyed by the autoimmune machine, and as a result, the foot_insulin could not be secreted. The other type of diabetes is non-Tengsu-dependent diabetes (n〇n_insuiin_depen (jent diabetes 6 200927158 mellitus 'NIDDM)', also known as type 2 diabetes, formerly known as adult-type diabetes; it is caused by the innate constitution, plus The factors of the environment of the day after tomorrow: obesity, lack of exercise, stress, etc., lead to abnormal insulin or Wei, the body can effectively make the island, this situation is called (insulin resistance) (Wahab ΝΑ, Weston BS, Roberts T. and

Mason R.M., 2002, Connective tissue growth factor and regulation of the mesangial cell cycle: role in cellular hypertrophy. J. Am. Soc. Nephrol. 13: 2437-2445). Because diabetes is an extremely chronic disease, its terrible thing is that it can cause a variety of serious complications including dysplasia: the complications of New Zealand are the most serious coma, and most of the diabetes occurs in treatment; Between dyeing, bribery, and hands, the patient will be tired, weak, thirsty, and polyuria. Nausea and other prodromal symptoms, followed by oliguria, coma, deep breathing, breathing with a strange smell, blood pressure drop, etc., this is - _ emergency, if the patient does not receive proper treatment, the coma will deepen and die . 0 In terms of pain, 'anyone who has diabetes symptoms and has a blood stasis value higher than 200 mg/dL or fasting blood glucose higher than just mg/dL at any time indicates diabetes; if there is diabetes, but the blood is lower than the above The standard should be tested for sugar tolerance ((10)] coffee _t〇ier_cafe, 0GTT).目 • The urinalysis still cannot be completely treated by drugs. It must be controlled by diet, exercise and drugs at the same time. It is possible to effectively stabilize blood sugar to avoid or delay the occurrence of complications (Zhou Xin·, job 'd' lbeT n lyr, C ~ 〇n diabetes C〇mpllCati〇nS and 〇n the diabetes, Clm. Diabetes 22: 162-198). Due to the side effects and discomfort caused by the use of chemically synthesized western medicine, many people have turned back to seek to have lions, to treat these sensational traits, and to turn to the locals. Among them, the broken 7 200927158 cloth is a cure for hypertension. Local health care plants with functions such as antitussive and detoxification. The rag is belonging to the genus (10) genus, the scientific name is c_w__FOTstf, the English name is _mingCOTdia' SebastanPlumC〇rdia, the alias is broken, the tree is broken, and the fruit is for many years. The deciduous small tree or small shrub is native to Guangdong, Fujian, Hainan, China. The island, as well as Taiwan and other places, - distributed throughout Taiwan, China, the Philippines, Malaysia, India, Ceylon and Southeast Asian countries; Taiwan is distributed below the low altitude of 1000 meters to the flat. Faced in the early days of #湾, Qianpei, with the county's change, spread over the fields, hillsides and ® vacant land. Because of its vitality, unmanageable management and practical value, it is the fruit of Taiwan's ancient trees. When the fruit is ripe, the fruit is picked, soaked in water and washed, placed in steel about 5~6 small B. 'When cooked, list it', add salt, garlic, tomb and other ingredients, and then put it in the container. In 10 days, it becomes a good meal with a good flavor and has the effect of spleen and stomach. According to the medicinal botany published by the National Institute of Chinese Medicine, the efficacy of the rags is divided into three parts: 1. Bark · Indications for uterine inflammation, uterus prolapse, long-term injury, pulmonary hemorrhage, and elimination; Root: can stop sweat, cure high blood pressure; and ® 3_ fruit: with antitussive, slowing down, detoxification, and intestinal function. In the chemical composition, three alkaloids and n flavonoids and their glycosides were separated from the rags. · The five flavonoids of the towel were identified as isoflavone s〇rh_etin and kaempferol. ), quercetin (Quercetin), 5,6,4,_trihydroxy-3,-nonoxylated flavonoids _7_〇-mouse' plumose glucose bud (5,6,4, de ydroxyd^methoxyflmmeKX rhamnosylglucoside ), and 5,6,8,4'-tetramyl flavonoid _7_〇_rhamnoside (5,6,8,4'-tetramethoxyflavone-7-0-riiamnoside). 8 200927158 Flavonoids have been shown to have natural antioxidant functions, and can regulate immunity, which has inhibitory effects on cancer cells; according to Lin Zhengwei's research (Min 94, deletion promotion, although the induction of breast cancer cell proliferation by sex is discussed: Study on the activity of the structurally similar class of Huangqi compounds, Master's thesis of Erbei Medical University) 'Investigate the inhibition of breast cancer cell proliferation between different structures from the similarity of the twenty-sugar composition_yellow compound. The experimental results found that 3_〇h Huang Wei (10) η

Intestinal (4), Lingshi aempfe spider material domain, expected to destroy m) and bark flavin (querce (4) can effectively block the male cellulite growth factor (E2/Peng) induced by human breast cancer cell line mcf_7 (10) protein expression Inhibition of cell proliferation and malignant transformation; and Guo Baochen pointed out in his research (Min 92, the expression of Μη protein in human lung cancer cells and chicks: - the oxygen seam supplier has no nucleus side, Guida (four) scholar paper), When treated with quercetin (q臓etin) _ 〇 )) for 24 hours, the concentration of lung cancer cells decreased with the increase of concentration, and the cell growth and cell growth were inhibited. In addition, xanthine compounds have the effect of scavenging free radicals, resisting free radical damage to cells, and preventing cardiovascular diseases; high materials indicate in their research (Min%, isoflavones on the proliferation and migration mechanism of diabetic vascular smooth muscle cells) : Comprehensive review, Fu Jen University master's thesis), 70-80% of adults with diabetes die from diabetes complications - atherosclerosis, and the migration of vascular smooth muscle cells is an important factor in the development of arteriosclerosis, smoothing the residual cells The twins are regulated by the blood-stained scorpion and (10) _ _, _ Mitogen aetiyity prctein (MAPK) pathway can upregulate platelet growth factor and endothelin; and isoflavones are naturally occurring urethane receptor inhibitors, research It is shown that isoflavones can inhibit the conduct of the road grip, 9 200927158 For patients with diabetic cardiovascular disease, isozyme may inhibit the smooth proliferation and migration of blood t smooth muscle caused by platelet biosynthesis and endothelin by inhibiting the sputum conduction pathway. , thus reducing the rate of morbidity and mortality. Further, step by step, Astragalus compounds have also been found to have menopausal women's menopausal symptoms, prevent osteoporosis; according to Wu Kewei's research (Republic of China 92, to explore the growth of osteoblasts and bone cells of the same name, The influence of differentiation and physiological activity, Kaohsiung Medical University master's illusion, three kinds of different huangqiqi (four) fine η or daidzem, bl〇ch_ A or three isoflavin combined drug concentration, can promote the proliferation of osteoblasts before the cells and Differentiate the mature osteoblasts and promote the osteogenic effect of mature osteoblasts; and the three isoflavones can inhibit the growth and differentiation of the pre-existing cells and inhibit the formation of the susceptor. In addition, the three kinds of isoflavin can promote the osteogenic cell mineralization at the drug concentration of 1〇-6 M. The effect of 实验 他 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Three different yellow countries The following is the tendency to promote cell migration of osteoblasts before the cells; this study confirmed that isoflavin can promote osteoblast proliferation and maturation and inhibit the formation of rhythm cells to achieve the role of regulating bone metabolism. Zhang Yuyu, Li Pei Duan (Republic of China 77, Broken Cloth Hypoglycemic Effect and Chemical Composition) The chemical composition of the root side of the broken cloth includes p sitosterol > Bio Silk 'tang_' and can significantly reduce blood sugar and sputum in rats. Fat; and Huang Wenqi's 200927158 study pointed out that (Republic of China 69, analysis of the composition of rags and its cytotoxicity on the uterus, National Taiwan University Master's thesis), in the cell culture study also confirmed that the rags bark indeed Inhibition of the growth of cancer cells; in addition, Xiao Huimei et al. used water and methanol extracts of rags leaves to culture human hepatoma cell lines (HepG2), respectively, and found that the two extracts were at high concentrations (0_1 mg/mL methanol). Both the extract and the 〇·5 mg/mL water extract significantly reduced the cell viability of the liver cancer cell line (HepG2). Xu food contains important ingredients of soybeans labeled "beneficial cardiovascular health" 'Isoflavones can effectively lower low-density cholesterol (LDL) in the blood, and it is an indisputable fact to increase high-density cholesterol (HDL); thus, it can be seen that it contains a large number of The rags of the composition also have the potential to be used in the treatment of cardiovascular diseases and other related diseases. In the actual system, Mr. Rong (Mr. Rong) in the practical Taiwan group to discuss the method of taking the rags, in the treatment of uric acid, The domain service party and the post-service party are in the service part: you need to first put the broken cloth in the belly of the chicken, add water, drink soup and eat meat, and even serve h

After the service, the latter is: the rags roots and the chicken are simmered, ~ drink L meat, served until the record. In addition, the wrong money, miscellaneous, cloth cloth roots, arrest: root, Bai Xu breast milk, stinky jasmine root, corn must - boil, water ^ z ~ 'slag with water 5 bowls of 1 bowl of 'two decoction combined Divide three times for each meal; the part of ^_Μ ' needs to break the fabric with a layer of skin, white rough, pearl grass, three grass, shame root, white horse teeth together..., water 8 bowls Fry 3 bowls, add the pork chop meat to the slag, and take it in three times. ‘,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, And on 11 200927158, the rags of the rags are rarely mentioned by the world, only the rags are effective for acute nephritis. This shows that the method of knowing the gambling of the rags and descending the record is complicated, the steps are complicated, and the gamma-breaking cloth and the bark are caused by the growth of the leg and the age of the plant. Due to the rise of light food and vegetarian food, the value of Wei Wei breaking the cloth, and repositioning it, and driving the axis of silk rags, more and more people are eating, the area of the area is increasing year by year, and the price of the product is also increasing. Therefore, if you can develop the most suitable and least affected parts of the cloth plant to achieve antihypertensive, high uric acid and diabetes, it will make the application of rags more The industrial value, the cost can be high and low, 'will benefit more people suffering from high blood pressure and disease. It can be seen that there are still many shortcomings in the above-mentioned formula for treating high blood pressure, high uric acid and diabetes by using a rag plant, which is not a designer of goodness, but is improved. The inventor of this case secretly made the above-mentioned rags plant to treat high blood pressure, high uric acid and diabetes, and it was a new one. After many years of painstaking research, he finally succeeded in research and development. A medical composition that can reduce the body weight, reduce uric acid and prevent diabetes. SUMMARY OF THE INVENTION The purpose of the present invention is to reduce blood lipids. The purpose of the present invention is to provide a pharmaceutical composition for obtaining high-uric acid and anti-diabetes. This is the second month of the month - the purpose is to provide a pharmaceutical composition that is low in cost and effective in reducing blood fat, anti-hyperuric acid and anti-diabetes. 12 200927158 Achieving the New Zealand (4)--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ...the dapped leaf extract is fine as the solvent, at the appropriate temperature, the 咕 布 蝴 蝴 _ __ to η 嶋 percentage bones / dish can be 30 〇: to 121t, extraction The time is from % minutes to μ hours, and the detached leaves extract is obtained. ❹

The detached leaf extract can be directly used as a pharmaceutical composition for reducing blood fat, anti-hyperuric acid and anti-diabetes of the present invention, or with a pharmaceutically acceptable carrier such as a diluent, an excipient or a carrier. Formulated into various forms, such as: tablets, capsules, granules, solutions, sugar-polymerizing agents, etc.; in addition, the rag-packed extract can be further concentrated or dried, and then combined with pharmaceutically acceptable _, to f into each lion-type preparation. 5H diluent can be a polar solvent, such as: water, alcohols, ketones, esters or a combination thereof, preferably water, alcohol, water / alcohol mixture, physiological saline, buffered aqueous solution, buffered saline Wait. The excipient or carrier may be in liquid or solid form, such as: lactose, dextrin, starch, corn flour, sodium stearate, etc. The liquid excipient or carrier includes water, salad oil, wine, fruit juice and the like. [Embodiment] Example 1 Extraction of the leaf extract of the rags and preparation of the capsules The 120 kg rag leaves were washed with water and immersed in 2000 L of water at 1 Torr. (: 8 hours of extraction) and then separated by filtration to obtain the extract of the burr leaf. After concentrating the obtained burr leaf extract to 3.1 Kg, 'mix the appropriate proportion of the excipient (corn starch) and spray granulator The powder is prepared, and magnesium stearate is mixed, and filled into a rag fabric leaf extract capsule by a capsule filling machine 13 200927158. Example 2 Fragment analysis of the rag fabric leaves The component of the detached cloth leaf extract capsule is analyzed, and the component analysis result is obtained. As shown in the table, the results show that the rag extract has five major nutrients · protein, sugar, lipids, vitamins and minerals, and its mineral potassium content is as high as 5290 PPm, which shows that the leaves of the rags have diuretic effect. A broken cloth leaf extract composition analysis results 检 check g-test results unit test method heat

ND(MDL=2) 5290 ppm Analytical Coupled Spectrometer (ICP/OES) for Inductively Coupled Spectrometer (ICP/OES) Analysis to Inductively Coupled Spectrometer (ICP/OES) Analysis of Calcium 5270 ppm ND (MDL =2) ppm Analytical coupling of copper spectrometer copper tortoise 4.50 ppm (ICP/OES) for inductive coupling. Spectrometer (ICP/OES) analysis of 13.2 ppm for inductive coupling. Spectrometer (ICP/OES) analysis of ND (MDL) =2) ppm Phosphorus Inductively Coupled Spectrometer (ICP/OES) Analyze 664 ppm to Inductively Coupled Spectrometer (ICP/OES) Analyze Magnesium 553 ppm to Inductively Coupled Spectrometer (ICP/OES) Analyze Cadmium ND (MDL) =2) ppm Analyze the spectrometer (ICP/OES) by inductively coupled electricity 14 200927158 Ο

Inspection item test result unit test method iron 45.1 ppm Inductive coupling electric spectrometer (ICP/OES) is divided into sulfur 518 ppm to induce coupling electric spectrometer (ICP/OES) to divide citrus moth ND (MDL=2) PPm to induce coupling Electric spectrometer (ICP/OES) split vitamin A ND (MDL-3) ppm Remarks Vitamin C 16.2 ppm Remarks Vitamin D 62.93 mg/lOOg Remarks Carotene 66.3 ppm Remarks Folic acid 0.29 ppm Remarks Vitamin 0.4 PPm Remarks Vitamin b2 6.5 ppm Remarks Vitamin b6 ND (MDL=1) ppm Remarks Dietary fiber 10.36 % Remarks Vitamin Ε-α 33.7 PPm Remarks Vitamin Ε-/3 9.21 ppm Remarks Vitamin Ε-γ 11.1 ppm Remarks Vitamin Ε-δ 11.4 ppm —---- Remarks Acid test 16.7 ppm Remarks Organic acid (oxalic acid) 0.06 g/l〇〇g Remarks Chlorine ND: Below the method detection electrode (MDL). The measured value of the limit of 25.97 is expressed as "ND" mg/lOOg, and the test result is remarked -_1 3 δ Mainly its method detection limit Remarks: Water threat white i 豕 standard cns 5Q33臓4, 1984 food moisture Testing method". m China National Standard cns 5〇35 N6u6, 1986 "Inspection of crude protein in foods CNS 3449N6065, 1988 "Determination of dairy products - Quantitative analysis of protein non-poor goods J and crude fat · Reference Chinese national standard CNS 5〇36 N6n7, 1984 “Grey: refer to the Chinese national standard CNS5〇34N6ii5, contact: such as the test method of the month.” Carbonization, substances: According to the “Inspection Method for Food Camps in Taiwan” by the Department of Health of the Executive Yuan. Deducting the content of water, crude protein, crude fat and ash, etc." 100g edible portion sample 15 200927158 Heat · According to the "Taiwan Regional Food Nutrition Database" of the Department of Health of the Executive Yuan, according to the sample of 100g of crude protein The fat and carbohydrate content are multiplied by their individual known caloric coefficients of 4, 9, and 4. 'Sodium: Refer to China's national standard CNS 12869 N6231, 1991 r. Test methods for minerals in infant formulas - copper, iron, money, fierce, _, nano, resignation test." Vitamin A: 1. Standards Inspection Bureau of the Ministry of Economic Affairs of the Executive Yuan, 1990, Determination of vitamin A in infant formula. 2. CNS 8859 n6168, 1982. Vitamin B (Vitamin B!): 1. AOAC, 1984, Thiamine (Vitamin B〇in Grain products Fluorometric (Rapid) Method Final Action, pp. 837=838. 2. Analytical procedures for the Determination of vitamins in Multivitamin preparations, Fluorimetric Determination of vitamin Bi (Thiochrome Method pp 35-36, ROCHE). Vitamin B2 (Vitamin B2) . Analytical procedures for the Determination of vitamins in

Multivitamin preparations, Fluorimetric Determination of vitamin B2, pp. 39-40 ROCHE. ’ 'Vitamin B6: USP version 21 ρ· 276. ASSAY FOR Pyridoxine Hydrochloride. Vitamin C: Xiaogao, Daozizi, Shijialong, Ueno Gentleman, Suda consumption, 1985, Quantification of vitamin C, Vitamin 59451-457 曰本日本昭昭电工股份有限公司. Vitamin E: Speek, A.J., J. Schrijver and W.H.P. Schreurs, 1985, “Vitamin E Determination of some Sedd Oils as Determined by High Performance Liquid Chromatography with

Fluorometric Detection", J. of Food Sci., Vol. 50, pp. 121-124. Vitamin D: Detemiined by Folch, et al. (1956) fat extraction method, NaOH saponification and BSTFA dericatization and GC-MS determination. -Carotene: Journal of Food Protection, Vol. 56, NO. 1 Page 51-54 (January 1993) Quantification of Provitammin A Compounds in Chinese Vegetables by High-Performance Liquid Chromatography. Final Acid (Niacin): AO AC, 1984 , Niacin and Niacinamide in Drugs, Foods, and Feeds colorimetric Method pp. 841-842. Folic acid: according to a. AOAC, 1990, Folic acid (Pteroylglutamic acid) in Vitamin Preparations, Microbiological Methods, Sec. 944, 12,1082-1083 b. Kirsch, AJ and Chen TS (1984) Comparison of conjugase treatment procedures in the microbiological assay of food folacin. J. Food. Sci. 49: 94-98. c. Ball, GF.M. (1994). Water -soluble vitamin assays in human nutrition, pp. 351-355. Oxalic acid, gas: commissioned by the Food Industry Development Research Institute of the consortium. The nutrient content of the food and other common foods is shown in Table 2; compared with these common fruits and vegetables and food, the nutrient content of the leaf extract of the rags is significantly higher than that of these foods, as shown in Table 3; For example, the potassium content of the extract of the burr leaf is 16 times that of sapwood in 200927158, 48 times of Wendan, 4.4 times of lycopene, 44 times of lemon, 4.4 times of 8.1 L of grape, and watermelon. 5 3 times, 3 5 times of the music, and 2.9 times of the 5.29 times of the carambola; the leaf extract of the rag is rich in nutrients. ❹ φ Table 2 ingredient content table (unit: mg)

Leaf extract nutrient composition is a comparison table of other foods. Table 3 Broken cloth

(Unit: multiple) Zinc Iron Vitamin Β 2 Dietary fiber 13 132 45.1 32.5 10.36 17 200927158

The rag aggregate extract prepared by the example was supplied to a tester having diabetes. After paying 4 _ days), after taking the test subject's technical solution, _ after eating blood > T, t «m^t^CGluoose fasting);; after the fasting, the glucose concentration in the liquid is attacking mg/dL After the test, the blood concentration in the blood after the fasting was 135 mg/dL, indicating that the drug composition provided by the bribe can reduce blood fat, anti-hyperuric acid and anti-diabetes, and indeed has blood sugar lowering. effect. Example 4: Adjusting Blood Glucose Function Test _ Animal Test 1. Test Materials and Test Methods This test is based on the "Test Method for Evaluating Blood Glucose Function of Healthy Foods" published by the Department of Health of the Executive Yuan, using Wistar rats as test animals, and Hyperglycemia was induced by Nicotinamide and Streptozotocin (STZ) (non-insulin-dependent (type 2) sugar 18 200927158 urinary animal); after successful induction, Example 1 was administered daily. The obtained burr leaf extract (ie, test substance) was continued for 8 weeks; by observing items such as fasting recording, glutamate, glycosylated hemoglobin (HbAlc) or other biochemical analysis, and each data was verified by spss biostatistics. The number of Owy ANOVA in the software ^Dunean, s shouted as (four) Qing _ test method to compare the difference between the test group and the control group 'to assess whether the test substance has the effect of adjustment record. U test animals and breeding environment: 1-1.1 Test animals: Wistar rats 1丄2 Animal source: National Taiwan University School of Medicine Experimental Animal Center 1.1.3 Animal Sex: Male 1.1.4 Feeding conditions: a. Temperature: 22 soil 2 0C b · Relative humidity: 55 ± 5% c · Illumination: 12 hours of light and dark cycle (〇7: 〇〇~19: 〇〇) d· Feeding conditions: 2 cages U.5 Drinking water: free to drink I.2 Induction of Type 2 Diabetes: Eight-week-old rats were fasted for 15·24 hours, and then weighed separately, each of which was given 200 mg/kg of the amine by abdominal cavity/shot ( s chat ac., general), after 15 minutes, then the main = her succession _; after the butterfly period, the wooden test in the air for 24 hours) blood sugar value, if the super (four) ball is considered to induce success, 19 200927158 The test substance can be started to be administered.

The dose per kilogram of body weight of the rat = the recommended dosage of the human body is calculated by the Department of Health's formula. The rat dose is 〇.1〇4 g/kg. Set (60kg) X 6.25. Take per person per day

1-4 Animal observation, test items and methods: 1A1 clinical symptom observation: daily clinical observation during the test, and record whether the animal has different symptoms or death. (4) Dynamic _ heavy: The domain circumference and the amount of t-days are recorded in the weight of the shaft. 1A3 feed consumption: fixed weekly during the test period. I·4.4 Sample collection and treatment: After 8 weeks of age, the animals were sacrificed. The animals were fasted (10) hours before sacrifice, and their blood was sacrificed and analyzed. 1.5 Glycated hemoglobin detection and analysis: Glycated hemoglobin is the peak evaluation of the urinary hamster 8 _ domain control succession monitoring indicators. The blood sample is injected into a collection tube containing acetaminophentetraacetic acid Α anti-coagulant ▲ agent, such as ❿ 似, and then measured by high-performance liquid riding method (HPLC; BiG_RadVariantll). 1.6 Blood glucose measurement: use Bayer's AscensiaTM Fan^#2/ CONFIRM/ Glucometer® Melon Blood Glucose Analyzer. After blood collection, use the capillary tube for 20 200927158 to use the blood sample to enter the test strip; the money sample __ difficult test strip of Portuguese The heterogeneous oxidase potassium ferricyanide reacts with Wei, and produces (4) New Zealand (10) (4) the concentration of sugar is proportional. 1.7 Glucose tolerance test (OGTT). Before the start of the experiment, the rat silk food for 15 24 hours. After the amount is recorded, the rats are given 0.5 g/kg glucose, and then the blood content of the tail of the rat is given to change the blood glucose levels at the first, sixth, 120 and 180 minutes after the sugar. <1 Φ 2 Test results 2.1 § Effect of test substance on body weight and intake: The results in Table 4 show that during the 8 weeks of feeding, the daily intake of the control group was 45 〇 〇 · 8 g, and the test group's feed per The daily intake is 44·3 g, and the intake between each group is mutual There was no significant difference (p>aG5); and there was no difference in animal body weight and body weight loss between the two groups. 〇〇5). After 8 weeks of examination, the change in body weight and intake amount ~ ' ----- - . -_____________ - smoked (g) end weight (g) weight loss (8) control group 45. 〇-^^7 " 241.8, 9.9 _5 type test group 44.3 i 〇, 8 980 δ 〇 - 1 > i ^ * * Note: The S7 data are all -3 234.5 ± 18.9 55.3 ±6.9 2.2 The effect of the test substance on the glycated gray pigment. According to the test of Table 5, <4, the fruit is not after 8 weeks of feeding period. The glycated hemoglobin in the experimental group was 6 4.2% and there was no significant difference compared with the glycated hemoglobin 3 soil (4) in the control group ^ > 0·05) 〇21 200927158 The five white rats were fed with different concentrations of substances for 8 weeks, and the glycated hemoglobin Shadow group animal number

II --------—-—J-- HbAlc (%) Control Group 17.6 12.6

III

IV

Mean ± SD rate of change (%) a --------- 15.9 11.4 23.2 11.3 17.3 ±2.2 17.6 ± 4.2 18.3 29.3 11 - Test 2.3 Effect of test substance on fasting blood glucose values: +1.4 Table 6 results are shown in At the 4th, 6th and 8th week of feeding, the fasting blood glucose level of the test animals was measured. 'The ingestion of the test substance for 8 weeks was the same as that of the control group. The test group decreased by 3 8%. However, there is no statistically significant difference 〇〇5).

❹

Effects of fasting blood glucose levels on white rats at different concentrations for 8 weeks. Animal number / mg/dL π ΠΙ iv Mean ±SD rate of change (〇/0); ❹ 234 292 295 234 402 400 305 311 309.0 ± 34.7 309.3 ± 34.4 +1.4 284 394 374 338 400 396 388.5 ± 5.9 337 399 367·0 ± 17· 1 -5.5 434 330 449 399 403.0 ±26.5 •2.9 386 389 377 414 391.5 ±7.9 391 392 362

363 346 377.0 ± 8.4 362.8 ±7.8 -3.8 22 200927158 2.4 Effect of test substances on sugar tolerance test: In the 8 week feeding period, the test animals were measured at 4, 6 and 8 weeks, respectively, and the test group and (4) group (10)) (4) Wide re-entry: The area under the rising curve is recorded, and the glucose uptake curve is observed at 4, 6 and 8 weeks for the animals ingesting the test substance. The area under the lower than the control group decreased by 8.1%, 2.3% and 1.6% respectively. 3. Summary: ❹ The results of this test showed that the daily intake of 伽. 15 g/kg of test rats fm After 8 weeks of burr leaf extract, there was a downward trend in the online blood test and the test for the test of the amine and the chain of sputum (the second type (non-filament) induced by Qing. The burlap leaf extract shown under the conditions of this test has a partial blood sugar-regulating ability. Example 5: Reducing uric acid function test _ human test The example - obtained rag fabric leaf extract is provided to two persons with uric acid High testers (testers A, B) take 4 weeks (28 days) The urine samples of the test subjects A and B were tested to measure the uric acid concentration in the urine; the results are shown in Table 7. The test subjects A before the test (test day), the urine The concentration of uric acid was 13 tons 胤. After 4 weeks of testing, the urinary g of the K solution was 7.9 mg/dL, while the subject B was in the urine before the test (test day). The concentration of uric acid was 7.8 mg/dL. After 4 weeks of testing, the concentration of uric acid in the urine was 63 mg/dL. It shows that the pharmaceutical composition of the present invention which can reduce blood fat, anti-hyperuric acid and anti-diabetes does have Reduce the effect of uric acid. 23 200927158 Table 7 Broth-leaf leaf extracts reduce the result of uric acid test uric acid concentration (mg / dL)

Tester A Tester B Before the test (day 0 of the test) After the test (day 28 of the test) 13 7.8 7.9 6.3 ❹

Total cholesterol before (test day 0) test (tests 28th, 318 186)

Test Materials and Test Methods Example 6 Test for lowering blood fat function - human test The shredded leaf extract obtained in Example 1 was supplied to a tester having hypertension. Because of the high total cholesterol and triglyceride, it is an important risk factor for cardiovascular diseases such as coronary heart disease, stroke, and hypertension. Therefore, the subject is administered the pharmaceutical composition of the present invention. After the week (28 days), the blood of the test subject was fasted, and the concentration of total gallbladder ' and triglyceride in the liquid solution was measured to evaluate the antihypertensive effect of the pharmaceutical composition of the present invention; As shown in Table 8, the subjects' blood total cholesterol and triglyceride concentration were 318 mg/dL and 胤 前 before the test (the first day of the test), and the blood was tested after the test 4 The concentrations of total cholesterol and triglyceride are 186 mg/dL and mg/dL, respectively. The pharmaceutical composition of the present invention for lowering blood fat, anti-hyperuric acid and anti-diabetes has the potential to reduce the risk of hypertension. Factors and the role of antihypertensive. Table 8: Results of uric acid test by burlap leaf extracts Blood fat concentration (mg/dL) 24 200927158 This test is based on the “Evaluation method for regulating blood lipid function of healthy foods” published by the Department of Health of the Executive Yuan. The hamsters were employed as the test animals, and the serum lipid value of the animal induced by the 胄 饲料 饲料 ' 钢 钢 钢 钢 钢 所得 所得 所得 所得 所得 所得 所得 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 Blood lipids, and the data are carried out by 〇ne_way an〇va. First, there is a significant difference in the appearance of the ten-knife, and then Duncan, s mu〗tiple_range is used to compare the differences between the groups. The face change was used to evaluate the effect of the test article on regulating blood lipids. 1.1 Test animals and breeding environment: 1.1.1 Test animals: Syrian hamster (Syrian hamster) 1.12 Animal source: National Experimental Animal Center of the National Experimental Research Institute of the Foundation 1 · 1.3 Test animal strain selection Reasons: The role of hamsters in liver lipid metabolism The human body is the most consistent' and is the experimental animal recommended in the specification of the Department of Health's "Evaluation Method for Adjusting the Money of the Foods". 1.1.4 Animal sex: Male 1丄5 Feeding conditions:

a. Temperature: 22 ± 2 〇C b. Relative humidity: 55 ± 5% c · Illumination: 12 hours of light and dark cycle (〇7: 〇〇~19: 〇〇) d· Feeding status: 2 1 cage U .6 Feed··Control group ie the test group (containing 〇.3% test substance) The feed composition and preparation are as shown in Table IX. Modified with a fine _93M based feed formula, 25 200927158 modified the taste to 1G% soybean oil and added α2% biliary domain to provide animal essential fat ', 'the experimental animal produces 6 blood wax, the added fat from the Deducted from the percentage of corn house powder in the original application-through feed. Table 9 Table of feed ingredients

Feed ingredient group------_ test substance control group------- test group 0.30 Cornstarch 40.369 40.08 Dextrinized Cornstarch 15.5 15.5 Casein 14.0 13.992 Sucrose 10.0 10.0 Soybean oil 10.0 9.997 Alphacel, non-nutritive bulk 5.0 5.0 AIN-93M-MX 3.5 3.5 AIN-93M-VX 1.0 1.0 ' Choline bitartrate 0.25 0.25 L-Cystine 0.18 0.18 Tert-Butylhydroquinone 0.001 0.001 Cholesterol 0.2 0.2 Total 100.0 ~—--- 100.0 1. The feed formula is based on ΑΙΝ-93Μ, Used in caries experimental animals (Reeves, 1997). 1.1.7 Drinking water: Free to drink. 1.2 Test substance dose and test group: Test group feed type a Feed food quality dose (%) ' ~~_ Only control group high fat feed --_ 4 Test group high fat feed test substance 0.3b ~---- 26 200927158 a : Modified with AI^3^ basic thank-you formula, the fat was modified to 1〇% soybean oil to become oyster sauce, drink & to induce high blood lipids in the test animals. The added fat, deducted from the percentage of pre-powder. After 6 weeks of experiment, sacrifice animals to carry out various points. The original amount of 93 Μ feed b: dose ^ 士 · calculated by the adult per serving dry weight 500 g, with the recommended intake per person as the benchmark '? The amount of food intake. The lion's χ 1〇〇% = 〇.3%. 0.3% of the test substance was added too much, and the corn house powder in the control group feed was replaced by its composition. "Feed Animal Observation, Test Items and Methods: 1.3.1 Clinical Symptom Observation: Clinical observations were made daily during the trial and animals were recorded for abnormal bed symptoms or death. 1.3.2 Animal Weighing. Animal weight was measured and recorded weekly and on the day of sacrifice during the trial. Ο

1.3.3 Feed consumption: The feed consumption was recorded periodically during the test period. 1.3.4 Sample collection and treatment. After 6 weeks of feeding, the animals were sacrificed and the animals were fasted for i2_i6 hours before sacrifice. Sacrifice to collect blood and analyze it. 1.3.5 Analysis of blood lipids: a. Serum triacylglycerol (TG): A reagent group for measuring serum triglyceride (purchased from RANDOX Laboratories Ltd.) was used, which was determined by the enzyme coloring method. The principle is as follows: (K〇ditschek & Umbrd, 1969): The product of triglyceride hydrolysis by lipolysis (iipase), ruthenium peroxide 2〇2), followed by catalysis by oxidase (peroxidase), with 4-aminophenazone and 4 -chlorophenol reaction, which produces a purple-red occupational-addition compound, and then uses an ELISA reader to measure the absorbance at a wavelength of 500 nm. Finally, the concentration of the serum triglyceride is converted by the absorbance of the standard. The formula is as follows: Mg/dL)=

Standard OD - Blank OD Sample OD - Blank OD Standard Concentration (mg/dL) 27 200927158 b. serum total cholesterol (TC): a reagent group (purchased from RANDOX Laboratories Ltd.) using serum total cholesterol The enzyme coloring method is used for the following principle. Ch()lesteiOl Educational Program Expert Panel, 1988): Peroxidase (H2〇2), a product of serum total cholesterol hydrolyzed and oxidized by enzymes, and then subjected to peroxidase. Catalytic reaction with 4-aminophenazone and 4-chlorophenol to produce a purplish red quioneimine compound, using an ELISA reader at a wavelength of 500 nm

The absorbance is measured, and finally the total cholesterol concentration is converted from the absorbance of the standard. The formula is as follows: Sample concentration (mg/dL) =

Standard OD - Blank OD Sample OD - Blank OD x standard concentration (mg/dL) c• serum high-density-lipoprotein-cholesterol (HDL-C) · Determination of enzyme action and colorimetry The principle is to first take a quantitative amount of serum and add the appropriate sinking agent. The chylomicrons, VLDL and LDL are immersed in the temple. After the action is completed, the centrifugation is performed, and the quantitative supernatant is taken and added to the reagent for measuring cholesterol, and the wavelength is determined at a wavelength of 5 〇〇 nm. The absorbance value 'Compared with the standard' is calculated to obtain the concentration of HDL_c. d·serum i〇w_density-lipoprotein-cholesterol (LDL-C): Using the principle of enzyme action and colorimetric determination, a certain amount of serum is added to the appropriate sinking agent to precipitate LDL. After the action is completed, centrifuge it, take the quantitative supernatant and add the reagent for measuring cholesterol in 200927158. Measure the absorbance at the wavelength nm, compare it with the standard product, and after calculation, turn the total coffee to check the red clear _ turn Value, the available concentration 2. Test results: 2.1 § The effect of the test substance on body weight, intake: Table 10 results show that in the 6 weeks of feeding, the control group of animals (4) daily intake Ο W. 7 soil 0_4 g 'and the daily intake of the test group was 5·5 ± g 4 §, the intake difference between the two groups was statistically not significantly different from each other> (9) 5); and each group _ body weight and weight There is no statistical difference in the amount of increase, etc. (p>〇〇5). Table 10 hamster meals (test group) / no silver food (group 4) test substance for 6 weeks, for body weight and intake

Amount of change

: All data are expressed by Mean Shi SE (n=4) b : It is a good repair of high-fat feed. Based on the L5 g test substance for the intake of dry weight per adult, the product accounts for (1·5/500) χ 100/〇 = 0.3% of the daily food intake. Therefore, this test is to add the test group feed 〇 3% of the test substance 0 2.2 test substance on serum lipids: The test results in Table 11 show that after the 6-week feeding period, the test group of serum triacid The concentration of glycerol (TG) was 146.7 ± 6.4 mg/dL 'Compared with the serum triglyceride (TG) concentration of the control group of 158.7 ± 16·2 mg/dL, 'in absolute value decreased by 7.6%, but statistically There was no significant difference (p>〇_〇5). 29 200927158 Table 11 hamsters foraging test substances after 6 weeks, the effect on serum biochemical values Animal number I II ΙΠ IV Mean ± SD rate of change (%) b TG (mg / dL) c -- ^ . 丨 ~ control group 134.4 167.4 165.8 167.2 158.7 i 16 2 Test group 141.5 154.5 141.3 149.4 146.7±6 4 -7.6 TC (mg/dL) 1——— Control group 317.3 371.2 306.8 319.2 328.6 i 28.9 Test □ 299.0 310.6 298.1 334.6 310.3 i 17 〇- 5.5 LDL-C (mg/dL) —1 — Control group 133.6 143.6 121.5 136.1 133.7 ±9.2 Test group 125.5 112.5 121.0 125.7 121·2±26Π -9.4 HDL-C (mg/dL) —- Control group 131.8 68.2 102.3 162.8 116.3 ±40.5 Test group 114.7 82.2 82.2 51.26 -29.0 LDL-C/HDL-C ----- Control group 1.0 2.1 1.2 0.8 1.3 : b〇.6 Test group 1.1 1.4 1.5 2.5 1-6 ina +23.1 500 g calculation The recommended daily intake of 1.5 g of test substance per person as the standard food, J intake frequency W) X dirty = 0.3%. The test is called the test group b: rate of change = (control group - test group) / control group X 100%. ❹ ❹ C month cholestyramine; TC: total biliary sputum; LDL_C: Jianlin egg _; HDLC: high density from the test results of Table 10 - shows the serum total cholesterol of the test group after 6 weeks of feeding period ( TC) concentration S 310.6 ± 17. 〇 mg / dL, and control, group Jinqing total cholesterol (TC) concentration of 328.6 ± 28.9 mg / dL after the ratio 'has a 5.5% decline, but statistically No significant difference ^ > 30 200927158 0.05). From the test data in Table 11, the serum low density lipoprotein cholesterol (LDL-C) of the test group was 121.2 ± 6.2 mg/dL ' compared with 133.7 soil 9·2 mg/dL of the control group, although there was a 9.4% decrease. The situation was statistically not significantly different (p >〇.〇5); serum high-density lipoprotein cholesterol (HDL-C) concentrations were 82.6 ± 26.0 and 116.3 ± 40.5 mg in the test and control groups, respectively. /dL 'The results show no significant difference 7> 0 05). The LDL-C/HDL-C ratios for the atherosclerotic risk factors were further calculated in the control group and the experimental group, which were 1.3 ± 0.6 and 1.6 soil 0.6, respectively, but there was no statistically significant difference b > 0.05) 〇 3 Summary: The results of this test showed that hamsters ingested 0.3% of the test substance (ie, the dipper leaf extract obtained in the example) for a period of 6 weeks, which slightly reduced serum triglyceride (TG). The total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) decreased by 7.6, 5_5, and 9.4%, respectively, but there was no significant difference in the increase of serum high-density lipoprotein cholesterol; therefore, in this test The burr leaf extract under conditions has the ability to partially regulate lipids in the blood. The invention provides a pharmaceutical composition for reducing blood fat, anti-hyperuric acid and anti-diabetes, which has the following advantages when compared with the conventional formula: 1. The invention provides the blood fat reduction and anti-reduction The high-uric acid and anti-diabetic pharmaceutical composition is made of rags, so it does not have the destructive influence of roots and bark-like wood growth, and the material is fresher than the roots and bark, which can save labor. Therefore, the cost of materials can be greatly reduced. 31 200927158 2. The invention provides a pharmaceutical composition for lowering blood fat, anti-hyperuric acid and anti-diabetes, which has the effect of partially regulating grees, uric acid and blood sugar without the need of other prescriptions. It has the potential to develop scientific towel medicines for antihypertensive, high uric acid and diabetes. - i 顺 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ It should be included in the patent scope of this case. ''r, Shangshang 4' This case is for the sake of 1 - can reduce the blood lion, anti-caries and anti-diabetes medicine _ things are indeed _ 'and the stomach ship said that the body sweater effect, should have fully met the new Sexual and progressive statutory invention patent requirements, 提出 apply in accordance with the law, and ask your bureau to approve the invention patent application, in order to invent invention, to the sense of virtue. [Simple description of the diagram] ® - The effect of the test substance containing the uncontrolled substance on the glucose tolerance after 4, 6 and 8 weeks: _ 4 weeks __ the results of the test group; the 6-week control group The results of the sugar tolerance test of the sputum test group; (the results of the sugar tolerance test of the control group and the test group at the 8th week.) Figure 2 shows the rats under the control of the blood glucose rise curve after 4, 6 and 8 weeks. Area representation. [Main component symbol description] No 32

Claims (1)

200927158 X. Patent application scope: 1. A pharmaceutical composition that can reduce blood fat's resistance to high uric acid and anti-diabetes, including: CoWiWc/zotomaForstf· leaf extract and pharmaceutically acceptable carrier. 2. A pharmaceutical composition for lowering blood fat, anti-hyperuric acid and anti-diabetes as described in the first paragraph of the patent application, wherein the detached leaf extract is treated with an appropriate proportion of water as a solvent, at a suitable temperature It is obtained by extracting for a while. Ο 3. The therapeutic composition for lowering blood fat, anti-hyperuric acid and anti-diabety according to item 2 of the patent application scope, wherein the ratio of the leaf of the rags to the solvent is 1 〇: ! to ^ : Chuan (weight volume) Ratio, w/v) 〇 patent application fine as described in item 2 can reduce blood fat, anti-hyperuric acid and private 4. such as music composition, wherein the extraction temperature is 3 〇. 〇 to 121 it. 5. "Please refer to the second paragraph of the patent scope to reduce blood fat, anti-hyperuric acid and anti-diabetic pharmaceutical composition, wherein the extraction time is from 3 minutes to 5 hours. ^Applicable to the patent described in item i Reducing blood fat, anti-hyperuric acid and anti-diabetic medical pro-forms, wherein the rags and leaves can be taken in a step-by-step manner, and then combined with the music-acceptable surface to prepare various forms of preparations. 7. (4) Na Gang 6 side of the end of the $, anti-Qianqing urinary medical composition, which can be tablets, capsules, tablets, solutions, difficult agents, etc. • ^ Sina (4) red Electrolyzed, degraded and anti-diabetic composition, wherein the carrier which is simply acceptable is dilute, excipient or carrier. 4 Lina 8 pays for the rest of the body, the medicine of the filthy urine 200927158 A pharmaceutical composition, wherein the diluent is a polar solvent, including water, physiological saline, a buffered aqueous solution, a buffered saline solution, an alcohol, a ketone, an ester, or a combination thereof. 10. As claimed in claim 8 a medical-drug composition capable of lowering blood fat, anti-hyperuric acid and anti-diabetes, wherein the excipient Or the carrier may be in a solid form, including lactose, dextrin, starch, • sodium stearate, etc. 11. The pharmaceutical composition for reducing blood fat, high uric acid resistance and glycocalyx resistance as described in claim 8 And the excipient or carrier may be in liquid form, including water, salad oil, wine, mashed juice, etc. ❿ 34