TW201041587A - A pharmaceutical composition for enhancing insulin sensitivity and treating diabetes - Google Patents

Abstract

The present invention provides a pharmaceutical composition for treating diabetes consisting essentially of Ramulus Cinnamomi, Radix et Rhizoma Rhei, Semen Persicae, Radix Rhizoma Glycyrrhizae, and Cordyceps. The present invention also provides a use of a composition consisting essentially of RamulusCinnamomi, Radix et Rhizoma Rhei, Semen Persicae, Radix Rhizoma Glycyrrhizae, and Cordyceps, for manufacturing a pharmaceutical composition for treating diabetes Type II.

Description

201041587 VI. Description of the Invention: [Technical Field to Which the Invention Is Present] The present invention is (iv) a composition for treating a second diuretic (IV). [Prior Art] The prevalence of disease in beans has a tendency to increase rapidly, and the proportion of increase in sputum is the highest. The second type of diabetes, Tian Shi also did not move, but one of its important characteristics is "insulin anti-Ο Ο 丄 丄 μ μ '1, type 1, urinary disease and abnormalities of the receptor gene, Islet body, endocrine hormones, etc., have recently been considered to be closely related to obesity (Oiapman MJ., Diab VaseDis fe, 2007, Suppl 3:5-8) 〇 (10) The treatment of type 1 diabetes is to control diet, exercise, and Sugar and islet storage are the main agents, but (10) island remnant (insulin ^ ί is related to abnormality of pancreatic A receptor, - general blood loss to promote the time limit of Tengdao ^ secretion, depends on ^ Weixin (insulinsens leg Milk, the study of type 1 diabetes has attracted attention from all walks of life. Eight present = available for the lion's Tengdao cut-sensitive surface ship, and the effect of the silk is not enough, especially in the long-term use of western medicine Tengdao sensitizer, It may also lead to the exhaustion of the viscera. At the same time, the side effects of the drug, such as heart failure, hepatotoxicity, and the large medical cost, have many adverse effects on the use of the patient. Therefore, the effect of the low side effect is increased. It is an important and urgent problem to treat type 2 diabetes. SUMMARY OF THE INVENTION The object of the present invention is to provide a pharmaceutical composition for treating diabetes, which is mainly composed of the following components: Guizhi (brother (10), rhubarb (such as et Rhizoma Rhef), peach kernel (semen persi'cae), sweet萆 (such 乜(乜)(10)〇Gfycyrrhizae), and 冬泰夏萆(c〇rdyCepS). According to the invention, the pharmaceutically acceptable kinetic can be added as needed. Sensitivity 'to achieve the effect of treating diabetes, especially type 2 diabetes. The present invention further provides a composition for the preparation of a pharmaceutical composition for treating diabetes, wherein the composition is mainly composed of the following components: Ramulus Cinnamomi) 'Radix et Rhizoma Rhei, Semen Persicae, Radix Rhizoma Glycyrrhizae' Cordyceps. [Embodiment]

The present invention is mainly developed as a pharmaceutical composition for treating diabetes by discovering a combination of a Chinese medicinal material and having the effect of improving insulin sensitivity without the side effects of a general insulin sensitizer. In one aspect of the invention, there is provided a pharmaceutical composition for treating diabetes, which is mainly composed of the following components as an active ingredient: Guizhi (Cinmmomi), Fading (Radix et Rhiz〇ma Rhef), Peach kernel

Persicae) 'Radix Rhizoma Glycyrrhizae, anti-winter l grass' and add a pharmaceutically acceptable carrier. According to an embodiment of the present invention, the active ingredient of the pharmaceutical composition is mainly composed of the following proportioning ingredients = 1 / 25% cassia, 30 to 40% rhubarb, 丨 5 to 25 ❶ /. Peach kernel, 15~25% licorice and 5~10% Cordyceps sinensis. According to an embodiment of the invention, the pharmaceutical composition comprises about 20% cassia twig, about 35% rhubarb, about 2 〇 〇 / 〇 peach kernel, about 2 〇% licorice and about 5% Cordyceps sinensis. w The term “diabetes” as used herein refers to type 1 diabetes, type 2 diabetes, or non-pancreatic A-dependent diabetes. According to an embodiment of the present invention, a pharmaceutical composition can be used for the treatment of type 2 diabetes, which solves the currently problematic problems. This article refers to the "improvement of insulin sensitivity" - the word refers to the combination of = pancreatic hormone and its receptor, so that silk fibrosus rides hypoglycemia, gold fat = serum protein, sugar high pancreas county, repair: increase The number of secret islands in summer, or the promotion of the skeletal muscle glucose transporter 4 (GLUT4) gene = "therapeutic / melotherapy" - the same means that the diabetic patient will receive the effective dose of 201041587 of the pharmaceutical composition of the invention, Changing, correcting, promoting or affecting the patient's diabetes mellitus and resistance can also be improved. The tendency of urinary symptoms, and insulin resistance, medicine 具有 具有 增进 增进 增进 ☆ ☆ : : : : : : : : : : : : : : : : : : : : : : : : : : 治疗 治疗 治疗 治疗 治疗 治疗 治疗 治疗 治疗 治疗 治疗 治疗In the meantime, according to an embodiment of the present invention, the ί effect is improved to improve eating, drinking, polyuria and weight loss. Ο ti tiif" Normally fine. Apparently, the pharmaceutical combination of the present invention has the effect of "diabetes the blood sugar in the serum of a diabetic patient, and is known as "Ramulus Cmnammm" applied to the pharmaceutical composition of the invention. The dry shoots of Cinnam〇mum cassiapresd are commonly used in various diseases such as colds, exogenous cold, rheumatism, neuralgia and other shoulder and joint pain, palpitations, diarrhea, weak body and weak pulse. Rhodamine (Radix et Rhei), which is suitable for use in pharmaceutical compositions, is a plant of the family Polygonaceae. It has a bitter cold and has the functions of attacking laxative, purging fire and detoxification, promoting blood circulation, dissolving heat and dampness, and modern use for viruses. Hepatitis, acute cholecystitis, pancreatitis, etc. In the present invention, rhubarb can be Rheum palmatum L., Rheum tanguticum Maxim, ex BALF> or medicinal rhubarb (Rheum officinale) Dried roots and rhizomes of Baill.) + Semen persicae suitable for use in the pharmaceutical composition of the present invention, Prunus persica (L.) Batsch or Pmnus davidiana (Carr.) Franch. Dry mature seeds The main function lies in promoting blood stasis, relieving laxatives, and is used in clinical treatment for underlying coke diseases, such as abdominal pain, vaginal discharge, irregular menstruation, etc. Modern pharmacological studies have shown that peach kernel has antihemolytic effect and weaker 5 201041587 hemolysis effect It also has a certain effect in the treatment of cough. The glycyrrhizae), ^ + used in the pharmaceutical composition of the invention is used for moisturizing and relaxing, neutralizing the remedy, relieving the main, and the bed is suspending the ulcer, dispelling the phlegm, and the second: poisoning (4) a variety of pharmacological herbs such as cough, secret, anti-oxidation, etc. The licorice used in the embodiment of the present invention is the Cordyceps sinensis which is suitable for use in the Inner Mongolian glutinous glutinous (5) Qing), is a real side of a shop, mainly found in China, the biological ergot fungus Cordyceps 'for the traditional use of nourishing life ^;:;: ί. It has Zifei Yiqi, Zengjing Bushen Blood, impotence, nocturnal emission, waist and knee soreness, virtual asthma, night sweats, ^ separation to asthma, nodules. Modern f studies from the Cordyceps sinensis, its chemical structure can be roughly divided into gland, polysaccharides, alkaloids , ring wins, mites, these active tumors, insecticides Immunomodulation, immunosuppression, anti-radiation and other pharmacological effects; used in several articles. "Cordyceps sinensis" includes natural Cordyceps, artificial cordyceps, such as quilt, spore, her *_, Aedes edulis _ ΓΓΡ) Silk body (cw township ^· coffee (4), η η mold {Paecdomyces cicadae (Mk[Uel ) s_ , the active ingredient isolated from artificial cordyceps, such as cordycepin, cordyceps sinensis, more brewing' The pharmaceutical composition of the present invention can be According to a conventionally known method, the above ingredients are treated and combined, and the addition is carried out. The term "hand-held" as used in the context of the handle" means that any standard pharmaceutically acceptable material may include, but is not limited to, saline, salt buffered sugar, water, glycerol, ethanol or combination. The pharmaceutical composition of the present invention can be prepared into any solid form suitable for oral administration 201041587, such as pills, capsules, granules, lozenges and powders; or in liquid form, for example: various drinks, solutions or suspensions in water Liquid or syrup. According to the present invention, one or more kinds of agents which are commonly used in the formulation of oral preparations, such as surfactants, solubilizers, stabilizers, emulsifiers, concentrates, pigments, sweeteners, flavor additives and preservatives, may also be added. . Anyone skilled in the art can add the appropriate excipients to the pharmaceutical compositions of the present invention in accordance with conventional techniques and knowledge. In addition, in the broad aspect of the invention, the use of the method for the treatment of a diabetes-drug composition is provided, wherein the composition is mainly composed of the following groups: ^f^fmRamuius Cinnam0mi), rhubarb (Radix et Rhizoma Rh岣) ^(Semen Persicae) > ^{Radix Rhizoma Glycyrrhizae) > ^ < Cordyceps. The "effective dose" _ word refers to the amount of use of the pharmaceutical composition of the present invention to achieve the above-mentioned one or more medical effects within the disease. The effective dosage can be formulated by a person according to the method of administration, the excipient used or the dosage of the pharmaceutical foot of the present invention for each 2 s day adult remedy:: on the other clinically used for treatment The effect of insulin sensitivity in urinary diseases can reduce the amount of diarrhea, which can reduce the side effects of western medicine. σ The present invention will be further exemplified by the following examples. $4 system, but not used to restrict the case 1 · Establish diabetes, atmospheric animals, sputum, group test animals: SDA mice, male, weight 12G~14G grams, provided by the Experimental Animal Center of Xizhou University of Traditional Chinese Medicine, = Ziyou 1223tic,: ^ Free access to food and water. / Stupidity is 40%~70%, SD rat adaptability is proud! After week, they were randomly divided into normal 201041587 group, control group, and comparison group (compared group of feeding components, including feeding Cordyceps sinensis (in this example, using Paecilomyces pallidum), rhubarb, cassia twig and peach kernel , three groups of comparison groups of rhubarb and cassia twig, peach kernel and licorice) and experimental group (one example of feeding the pharmaceutical composition of the invention: 20% cassia twig, 35% rhubarb, 20% peach kernel, 20% licorice and 5 °/ Cordyceps sinensis, divided into low dose, medium dose and high dose three groups). The normal group was fed a normal diet, and the control group and the experimental group were fed with high-fat and high-sugar diet (15% sucrose, 4% cholesterol, 0.3% cholate, 1% lard '10% egg yolk powder, 61% basic feed). After week, 30 mg/kg streptozotocin (0.25% in pH 4.2 citrate buffer, purchased from Sigma Corporation, USA) was intraperitoneally injected. After 3 days, the fasting blood glucose of 211 mmol/L rats was screened by micro-glucometer. Experimental rats. In the first phase of the experiment, except for the normal group (20 rats), the other groups from the diabetic rats were randomly selected from the control group, the comparison group and the experimental group according to the body weight and blood glucose. Two sputum double sputum (existing diabetes treatment medication) group. The subsistence tables for the experimental drugs are listed below. · Group name Gastric food (once per day/rat) One normal group (A) No control group (B) Distilled water (2 mL) Comparison group - Artificial Cordyceps group (C 4 mg Cordyceps sinensis comparison group - ventilating sputum group (D) 29 mg rhubarb comparison group - Huoxue group (E) 16.5mg cassia twig 16.5mg peach kernel comparison group - Huoxue ventilating sputum group (F) 29 mg large Yellow 16.5 mg peach kernel 16.5 mg cassia twig 16.5 mg licorice 201041587 Ο low dose experimental group (G) medium dose experimental group (Η) high dose experimental group (I) 14.5 mg rhubarb 8.25 mg peach kernel 8.25 mg cassia twig 8.25 mg licorice 2 mg Cordyceps sinensis 29 mg rhubarb 16.5 mg peach kernel 16.5 mg cassia twig 16.5 mg licorice 4 mg Cordyceps sinensis 58 mg rhubarb 33 mg peach kernel 33 mg cassia twig 33 mg licorice mg Cordyceps sinensis

The drugs for the abortion were prepared as a powder and mixed, and dissolved in a proportion of no hydrazine distilled water, and each of the doses listed in the table was once per ampere for 8 weeks. Example 2: Detection of various diabetes-related diseases improvement effects At the 8th week, each group was randomly selected to record 1 body weight, water volume, urine volume, and glucose tolerance test, and to test insulin and insulin. , glycated serum protein and blood lipid content. Basic physiological conditions The typical symptoms of diabetes are “three more and one less”, which is clinically characterized by eating more, urinating more, drinking more and losing weight. This experiment records the changes in the basic physiological conditions of the experimental rats before and after the third week of treatment. 201041587 The results are shown in L and Table II. The amount of drinking water, the amount of water in the comparison group and the experimental group were similar to those in the experimental group (P>〇.〇5); but the food intake began to increase in private 1: ~ i~ after 8 weeks of treatment, the drinking water in the control group, Urine volume, eating system fft increased 'and body weight was lower than the normal group (P < 0.01). The amount of water and urine volume of the experimental group of the same control group was increased: the amount was increased, and the body was added (corporate < 〇.〇ι). Compared with the middle dose experimental group, the comparison group found that the drinking water, urine volume, and daily intake of most rats increased: Weight reduction (/»<〇.〇. Compared with the medium-dose experimental group, the N, low-dose, metformin group had the same amount of water as the urine volume (house > 0 05); while the food intake increased, the body weight decreased (corporate <;〇.〇1 or corpse<〇.〇5). Dioxin double, compared with the medium dose experimental group, the two groups were equivalent in terms of water consumption, urine volume, food intake and body weight after treatment (p> 〇. 〇5). -A1 urinary rats in the second week and 篦8 weeks of drinking water and daily urine volume group water consumption (mL / day) urine volume (mL / day) Week 0 week 8 Week 8 of 0 week A 30.57±8.67 65.35±12.62 16.31±5.64 33.46±8.86 B 35.64士7.83 85.23±10.85# 16.84±5.26 55.67±9.19# C 37.61±7.57 68.18±11.34#aA 17.62±4.19 38.37±8.26#δΑ D 35.37±6.08 66.12±10.41#δ 15.17士4.09 40.21±10.37#αΑ E 34.68士5.92 72.38±8.19#δΑ 17.94±4.51 39.34±9.68#^a F 35.33 士8.31 68.67±11.49#δΑ 16.21±4.53 40.37±10.18 #δΑ G 35.97±9.02 65.67±12.95#δ 15.03±5_07 35.07±8.34#δ Η 36.89±7.39 63.68±13.02#δ 17.34±4·95 33.64±9.07#α I 34.51±8.62 66.54±11.18# δ 15.62±6.25 35.45±10.32#α J 37.91±7.61 65.54±10.63#δ 16.06 Soil 4.91 33.07±8.38#δ #Compared with the normal group (household <0.01) difference △Significant compared with the control group (household <〇.〇1) difference. ▲Compared with the middle dose experimental group (Ρ<〇.01) difference. 201041587 Inflammatory rats drink water and daily urine on the 8th week of the third week Quantity -___Drinking amount (mL/day)___Urine volume (mL/day) Week 8 Week 8 Week 8 Week 8 A 18.57±6.67 55.35±12.62 128.34±8.01 433.24±35.67 B 23.64±7.83 85.23 ±10.85# 126.84±39,46 358.67±27.19# C 25.64±6.57 68.18±11.34#δα 128.62土7.19 398.37±32.26#δΑ D 24.37±8.08 76.12±10.41#δ,4 124.17士8.09 385.21±29.37#δ^ E 22.68 soil 6.92 72.38±10.19#ai4 127.94士9.51 380.34±25.68#^Α F 25.33±7.31 68.67±11.49#δΑ 129.21±8.53 370.37±28.18#^Α G 24.97±8.02 65.67±12.95#^AA 126.03±9.07 405.07± 30.34#δΑ H 23.89±7.39 61.68±13.02#ώ 128.34士7.95 420.64±29.07#δ I 24.51±8.62 66.54±11.18#δα 125.62±8.25 386.06±26.32#δ^ J 24 .91±8.61 63.54±10.63#δ 129.06士 8.91 418.07±27.38#δ# There is a significant difference (/»<0.01) compared with the normal group. Ο △ was significantly different from the control group (P < 〇.01). ▲The difference was significant (p<〇 〇 1 ) compared with the middle dose experimental group. ▲ ▲ was significantly different from the medium dose experimental group (p < 〇.05). The glucose tolerance test should be kept in a fixed range of glucose. Second, it is called fasting blood glucose (FPG). After eating, the blood sugar level will increase. At this time, the post-glycemic blood glucose (PPG) is called 'but in insulin. Under the effect, the average person should return to the level of fasting blood glucose within 1 to 2 hours after eating. Diabetes patients who are unable to reduce their blood glucose levels by insulin due to insulin deficiency or insulin resistance are considered to have impaired glucose tolerance and high blood sugar. For the glucose tolerance test, the rats were bled from the eyelids for 8 hours before each sample was taken, and the FPG was measured with an Accuchek Advantage II blood glucose meter (Roche Ltd). Followed by intraperitoneal injection of glucose 2 g / kg, 2 201041587 hours of empty fruit as shown. The difference in the group's difference was significant (/><G.Gi) compared with the 1 hour blood glucose and 1 hour postprandial blood glucose. Compared with the control group and the different doses of the control group, the metformin group had the right difference, such as blood glucose and 2 hours postprandial blood glucose, which were lower than the control group, (#P<(X()1)° compared with each disassembled group, The fasting blood glucose of the dose and the group and the blood glucose after 2 hours of the meal were significantly reduced, and the ancient ones (△1). Compared with the low-dose experimental group, the fasting blood glucose in the middle and double-sputum group and the blood glucose drop after 2 hours after the meal (▲ State.01). Compared with metformin group, 'medium and high dose%> 〇; ^ low fasting blood glucose and 2 hours postprandial blood glucose effect is equivalent to wife III sugar stagnation _ rat glucose tolerance test results group FBG lh-PBG 2h -PBG (mmol/L) (mmol/L) (mmol/L) A 4.85 ± 0.65 8.56±1.07 4.68 Soil 0.57 B 11.90±1·06 16.84±3.57 16.59±3.06 C 8.65±0.84# 11.57±2.34# 10.18± 2.67# D 9.38±0.73# 11.34 士1.98# 10.34±1.67# E 9.24 士0.67# 12.86±2.67# 10.23±1.94# F 9.74 士0.84# 11.29±1.61# 10.08 士1.62# g 8.09±0.64# 10.23±1.28# 10.64±1.61# h 6.59±0.57#α^ 9.34士2.35# 8.01±1.17#aA I 6.84±〇.76#δ^ 10.06 Earth 1.54# 8.43±1.08#aA J 6.48±0.49#ΔΑ 9.75±2.6 4# 7.59±1.26#δΑ # is significantly different from the control group (i><0.01). △ is significantly different from each split group (i><〇.01). 12 201041587 ▲Low The dose test group was significantly different (p < 001) difference. Detection of gold albumin, blood lipids, insulin, glucagon and insulin sensitivity index

After the blood was taken from the abdominal aorta in the experimental rats, the content of triglyceride and triglyceride was determined by glycerol oxidase oxidase-peroxidase-4-aminoantipyrine and phenol method (Gp〇_pAp method).妩 and Wang Yusan, National Clinical Laboratory Procedures, Southeast University Press, 1997, second edition: 275, and determination of cholesterol, enzyme-peroxidase-aminoantipyrine and phenolic method (CH〇p_PAp method) Total Cholesterol Content (Recommended Method for Determination of Blood Lipid by Chinese Medical Association) (II). Determination of Serum Total Cholesterol Enzyme Method (Draft) [J]. Zhonghua Medical Heart Test Miscellaneous, 1995, 18 (3): 183-186. ). Blood was collected, and serum was isolated. Serum insulin and glucagon were detected by radioimmunoassay. The radioimmunoassay used in the test was provided by the Institute of Isotopes of the China Institute of Atomic Energy. At the same time, serum was used to detect glycated serum protein by fructosamine method (Zeng Weimin tetrazolium blue colorimetric determination of serum glycated albumin Nanjing University Press, 1995 first edition: 201-202). The insulin sensitivity index (ISI) is based on the calculation formula proposed by Li Guangwei et al. (Li Guangwei, Pan Xiaoren, Stephen L, et al., Chinese Internal Medicine 1993; 32 (10): 656-660). Insulin FIns) is expressed as the natural logarithm Un(l/FInSxFBG) of the inverse of the fasting blood glucose (FBG) product. The results of the above respective test items are shown in Table IV and Table v. In Table VI, the control group glycated serum protein: solid, were higher than the normal group, the difference was significant (suppressed. (1) ^ control, and compared with most of the split group and different dose groups, two 1, Serum serum, triglyceride, and total cholesterol were lower than 杵, and the difference was significant (#Ρ<0.01, ##/><0.05) 盥 抽 工 , , , , , , , , , , A double-pulse group glycosylated serum protein was divided into three parties and = 13 201041587 g decreased 'the difference was significant (A / x O. Ol). Compared with the low-dose experimental group than the parent 'medium, high-dose group experimental group, metformin group glycosylation serum The protein reduction was more significant (▲PcO.W, ▲▲pd.OS); while the reduction of triglyceride and total cholesterol was equivalent (/>>0.05). Table IV and rat glycosylated blood, tone Christine Glucose-containing serum triglyceride total cholesterol (mmol/L) (mm〇l/L) (mmol/L) A 1.85±0.54 — 0.82 ± 0.30 1.84 ± 0.17 B ____ 3.67 ± 1.23 2.56±〇.49 2·48±0.31 C 2.34±0.62# —----- ^54^=0-37# 2.21 Soil 0.27 D 2.43±0.71## —.一1.84 土〇·51## 1.94 ±0.37 E 2.93±0.51 — 1.51±0.67# 2.13±0.28 F 2.64±0.69## 1.43 Soil 0.53# 2,04±0.39 G 1.98±0.68# ----- 0.97 Soil 0.41# 1·74±0.26# H 1.27± 0.44#α^^ 0.86±0.48#δ 1.62±0.31# I 1.23±0.34#δΑΑ ---- 0.97±0.53#α 1.79±0.23## J 1.14±0.38#δΑΑ 0.72±0.51#Δ 1.53±0.38# # Compared with the control group, there was a significant difference (household <0.01). The material was significantly different from the control group (/><〇.05). △Compared with each split group (/>&lt ;〇.01) Difference ▲There was a significant difference (/><〇.〇1) compared with the low-dose experimental group. ▲▲ was significantly different from the low-dose experimental group (Ρ<0·05). ^ In Table V, the fasting insulin and glucagon in the control group were all in the normal group, and the difference was significant (/><〇.〇1). Compared with the control group, most of the split group And different doses of the experimental group, metformin group, fasting and gonadotropin, glucagon were lower than the control group, the difference was significant (#Ρ<〇.〇1). Compared with the comparison groups, the mid- and high-dose experimental groups and the two 201041587 plain pancreatic glucagon were significantly reduced, and the difference was = land (△ kebe). Compared with the low-dose experiment, the number of 3 Τ is significant (4):) pancreatic tissue

##/><〇 rm8 heterogeneity (#<0.01, group insulin sensitivity) ΐ ΐ 各 1 实 实 实 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、

ABCDEFG Η IJ content insulin insulin glucagon 姨 sensitivity (uIU / L) (ng / L), 14 index (ISI) 21.56 ± 3.72 34.31 ± 4.24 272.6 ± 53.4 ~ 542.7 ± 82.7 26.37 ± 2.64 # 384.4 ± 62.5 # ~25784±3.68# 423.5士54.1? 27.81±3.27# 469.1±61.8# 26.34±4.25# 427.1±51.7# -4.02±0.24 ^56±0.19~ ^3±0.32## -1Τ24±0.37~~ ^17± 0.28 -Τ〇1±0.36## _26.37±3.29# 405.4±41.8# ~23^9±2.68#δ 310.3±48.6#λ▲ 291.8±4^.1?δ-▲ 302.4±42.1^δ· 22.31 ±3.16#Α~2^Γ38±3.19#δ -4.56±0,39#α -4.37±0.34#δ -4.33±0.29#δ #Compared with the control group (Ρ<0·01) difference## There was a significant difference (Ρ<0·05) from the control group. △ is significantly different from each split group (Ρ <〇.01) difference 4.25±0.28#』 15 201041587 'Compared with low-dose experimental group (p<〇〇1) difference from Table I to Table v As a result, it can be seen that the disease of the present invention is typical of the symptoms of the disease, and can cause the blood sugar to glyceose glycosaminoglycan and cholesterol, and the blood is also significantly reduced. Among them, the medium dose and the high dose are good, and the existing urine is treated. The western medicine of the disease - metformin ", has the same effect, but does not produce any known side effects of the western medicine. Insulin resistance is one of the important targets in the treatment of diabetes, but there are currently few types of insulin sensitizers for clinical use. The high price and the side effects were not satisfactory to the patient. As observed from Table V, the insulin sensitivity index of the experimental group was more significant than the other groups, and it was found that the medical composition of the present invention can improve insulin sensitivity. Example 3: Detection of Insulin The second phase of the experiment was carried out by demonstrating the performance of the number 舆 skeletal muscle grape 裱 gene (GLUT4) to confirm that the pharmaceutical composition of the present invention has an effect of improving insulin sensitivity and treating diabetes. In the second stage experiment, 10 rats were taken as the normal group, and the animal model was established as in the example, and the body weight and blood sugar content were randomly grouped as follows (20 each): Group name stomach irrigation food (day/ Dahua) Normal group no __ control group distilled water (2mL) medium dose experimental group -----, / 29 mg rhubarb 16.5 mg peach kernel 16.5 mg cassia twig 16.5 mg licorice 4 mg bat moth Pseudomonas fuliginea stuffing 16 201041587 - -------------I--------- - Double-sputum group _14 mg metformin rats were fed once a day according to the doses listed above. The drug was continuously fed for 8 weeks. At the 8th week, rats in each group were randomly selected to detect the expression of hepatocyte membrane and the glucose transporter 4 gene. Hepatocyte membrane insulin receptor (InsR) quantitative analysis

At the 8th week after the drug was administered, the rats were sacrificed, the liver tissue was cut, and 4 volumes of homogenate (1 mmol/L NaHC03 and 0.5 mmol/L) were added.

CaC12, ρΗ7·5) A homogenate was prepared at 8000 rpm. The homogenate was diluted with 5 times homogenate, filtered through gauze, and centrifuged at 800 xg for 15 minutes. After centrifugation, the supernatant was collected and centrifuged at 27,000 xg for 20 minutes. Collect 3.5 mL of the sink sample. Add 70 g/L sucrose 7.5 mL (w/w) to make the final sucrose concentration of the sample 48 g/L. The sample was placed in the bottom of the centrifuge tube, and 9, 8, and 7 mL of sucrose solution of 45 g/L, 41 g/L, and 37 g/L were sequentially added. After centrifugation for 7 hours at 78000 xg, the 37 g/L and 41 g/L interface layers were collected, diluted with 1 mm 〇l/L sodium bicarbonate (pH 7.5), centrifuged for another 20 minutes, and the precipitate was collected and appropriately diluted. The membrane protein concentration was determined by the Lowry method (National Pharmacopoeia Commission, Third Edition of the Pharmacopoeia of the People's Republic of China [M]. 2005 edition, Beijing: Chemical Industry Press, 2005 · Appendix 30).

Receptor binding experiments were performed using a non-labeled ligand multi-point saturation method (Lowry OH, Rosebrough NJ, Farr AL, et al. Biochem, 1951; 193(1).265-275.). The experiment was carried out in an ice bath. The final concentration was 0, 0.015, 0.15, 1.5, 6, and 5 〇 nm〇i/L in the experimental tube.

Such as unlabeled insulin (Ins), each tube plus monoiodo-labeled insulin (〗 〖25 I-Ins) 83.3Bq, membrane protein 65pg' with 丨g / LBSA_〇 () 5mm 〇 1 / L • Tris-HCl The buffer is added to the reaction volume, and after mixing, it is shaken for 2 hours in ye. The multi-head cell harvester collects the receptor-ligand complex and rinses with distilled water. 17 201041587 3 times 'Radioactivity determination was performed with a γ§ decator (FJ22003150 type 'Swedish Pharmacia). Standard hs (concentration of 50nmol/L - ^ radioactivity is non-specific binding (NSB) 'The difference between sample radioactivity and NSB is specific binding (B); total radioactivity is the difference between T ' T and sample radioactivity is the free value (F) After obtaining the above values, perform data processing, first calculate B/F = (sample radioactivity - NSB) / (T-sample radioactivity). Think Y axis, RL is X axis, use SPSS statistical program computer software ... catchard fitting, respectively, to calculate the affinity constant (ΚΙ, K2) and the number of binding sites (R1, R2) of the high-affinity receptor and the low-affinity receptor on the cell membrane. The negative reciprocal of the two asymptotic slopes of the curve is the affinity constant The intercept of the asymptote on the X-axis is the amount of insulin bound by two different affinity receptors, representing the number of receptors that bind to insulin. GLUT4 gene expression measurement GLUT4 is mainly present in the cytoplasm of bone musculature, fat cells, A3, the role of glucosamine, only under the stimulation of insulin signal, to the cell membrane, to promote the sugar into the above tissue mm for g_gene secret hybrid detection, according to GLUT4 gene expression and insulin membrane receptor on the liver cell membrane number Open >, therefore understand the effect of insulin sensitivity. Diaphragm, rat, rapid separation of the double-armed quadriceps immediately placed in 4% paraformaldehyde fixed 4 small final slice is 5μηι thickness and dried.大彳nprobe and 胄(4)Wei miscellaneous 脳 脳 武汉 武汉 武汉 武汉 ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' 纽 纽 纽 纽 纽 纽 纽 纽 纽In normal.) the same, low affinity binding site pro 18 201041587 and the constant compared with the normal group helmet (wind 05), control near, the difference is not significant binding site private constant nd, low affinity transport 4 gene expression := r) The expression of the body 4 gene is high. The expression of the dimer 4 gene has no significant bone path muscle glucose transfer. GLUT^^ ::: 2 insulin sensitivity, and thus improve the insulin resistance group - eight called 'Ding, Ren Shengjiu VJLU 1 Swallow E Hepatocyte membrane insulin receptor performance ~~Guru~^ K1 mol/L (χίο·9) Κ2 mol/L (χΙΟ·8) R1 mol/mg (xlO·12) R2 mol/mg (xlO'12 ) Wu Siyi (average optical density) Normal group 13.54±4.78 14.68 ± 5.76 0·26±〇·13 3.35±1.38 0.57±0_04 Control 12_25士3.62 13.04±4.13 3.14±1.27 5.11±2.14 0.27 0.02 曱2曱曱 group 13.24±3.28 12.35 士5.02 5.57±1.54# 6.44±2.38## 〇.49±〇.〇5# medium dose experimental group 13.45±3.67 13.24±4.95 6.24±1.38# 6·69 Earth 2.13# 〇46士〇.〇4# Table VI Insulin receptor and GLUT4 gene K1: Affinity constant of 咼 affinity insulin receptor K2: Low affinity insulin receptor Affinity constant 201041587 R1: Number of high-affinity insulin receptors on the hepatocyte membrane R2: Number of low-affinity insulin receptors on the hepatocyte membrane # Significant (/><〇.〇1) difference compared with the control group. The material was significantly different from the control group (Ρ < 0.05). Example 4: Pathological observation of pancreatic sections After sacrifice of the rats in the first stage experiment, rat pancreatic tissue was taken, fixed with 10% nails, embedded in stone mortar, sliced and dried at a thickness of 5 μηι, and then subjected to General HE staining. Observing the type change of islets under the microscope and calculating the number of islet β cells, the results are shown in Table νπ. From the naked eye, it is found that the pancreas of diabetic rats is 'color pale and dark' compared with the pancreas of normal rats. The tissue is dry, and the tissue is thinned. ^Under the microscope, it can be seen that the normal rat islets are round or elliptical. The cell clusters are different in size, while the β cells are located in the center of the islets, and the nucleus is round and cytoplasm is abundant; The number of islets in the rats was significantly reduced, the remaining islets were atrophic, and the number of islet cells was reduced. Under high magnification, the islet cell nucleus was condensed and the cytoplasm was significantly reduced, which was degenerative (household <〇〇1). In the metformin group and the experimental group, the density of islets was significantly decreased, but the number of β cells was higher than that in the control group (ρ < 0·01). If the medium-dose experimental group was compared with the one-fold double-twisted group, the number of β-cells in the medium-dose experimental group was significantly increased (/»<0.01). ‘Tengdao β cells in general diabetic patients are damaged and degraded along with the disease process, resulting in insufficient insulin secretion. The pharmaceutical composition of the invention can help the repair of islet β cells, increase the secretion of insulin, and reduce the use of hypoglycemic agents. 20 201041587 Table VII Effect of islet β cell number ([士s) group number/field of view __^staining X 400 times) Normal group 58.20±15.30 Control group 35.50±13.51#A Diterpenoid group 42.17±12.06#ΔΑ Medium dose Experimental group——__45.58±15.06#Δ --------------^ 'J-1- a •K/xJTr /__\ # is significantly more significant than the normal group (p< 〇〇丨) The difference △ is significantly different from the control group (FO.〇1). ▲ The experimental group is more significant (/><〇〇)) Differences 熟知 Those skilled in the art will be able to Modifications and modifications are made in accordance with the embodiments in the spirit of the invention. It is to be noted that the invention is not limited by the scope of the invention disclosed in the appended claims. [Simple description of the diagram]

[Main component symbol description] None 21

Claims (1)

201041587 VII. Patent application scope: 1. A pharmaceutical composition for treating diabetes, which is mainly composed of the following components: MXRamulus Cinnamomi), Radix et Rhizoma Rhei, Semen Persicae, Ganzi (Radix Rhizoma Glycyrrhizae), Anti Winter & Grass (Cordyceps). 2. The pharmaceutical composition of claim 1 is mainly composed of the following components: 15 to 25% cassia twig, 30 to 40% rhubarb, 15 to 25% peach kernel, 15 to 25% licorice and 5 to 10 % Cordyceps sinensis. 3. The pharmaceutical composition of claim 1 which is mainly composed of the following ingredients: about 20% cassia twig, about 35% rhubarb, about 20% peach kernel, about 20% licorice, and about 5% Cordyceps sinensis. The pharmaceutical composition according to any one of claims 1-3, which enhances insulin sensitivity. 8. A pharmaceutical composition according to any one of claims 1-3, which increases the binding of insulin to the receptor. The pharmaceutical composition of any one of claims 1-3, which increases the absorption of glucose in skeletal muscle and fat cells and effectively reduces blood volume. 7. If the pharmaceutical compound is applied to any of the patent scopes f 1_3, the treatment of the disease is related to the improvement of insulin sensitivity. 8. If you apply for a medical composition of the __ _ _ _ _ _ ─ ─ ─ ─ ─ ─ ─ ─ ─ ─ ─ ─ ─ ─ ─ /, ° mjs: the pharmaceutical composition of any of the items - (4) paste of the pharmaceutical composition of the first item of the first item - the medicinal composition of the gamma 5 range, the pharmaceutical composition of which can be added to the first _3 shot The pharmaceutical composition of claim 9 is administered orally as a pharmaceutical composition of claim 9 in the form of a pharmaceutical composition of claim 10, which is administered orally. The composition of the composition can be used for the preparation of a medicament for treating diabetes, wherein the group is mainly composed of the following components: cassia twig (Vanix et Rhizoma Rhei), peach kernel (Semen) Persicae), Radix Rhizoma Glycyrrhizae > ^A^4(Cordyceps) For example, the application of Patent No. 4, the towel composition is mainly composed of the following % cassia twig, 30~40% rhubarb, 15 ~25 % peach kernel, Ο Ο 17. 用途 Patent scope 15 uses 'The composition is mainly composed of the following ingredients: about 20% cassia twig, % 0 / qingqing king to be about 20% licorice and about 5 % winter insect =. / ° Daqi, about % peach kernel, 18. If the patent application range is 15_17 sensitivity. Item - 'to enhance the island of Tendo 19. If the patent scope is 15_17, the combination of island and receptor The use of the item, which can increase the pancreas 20. If the application of the patent range 15_17 sugar in the skeletal muscle and fat cells ^ use, it can increase the Portuguese 21. As in the patent scope of the 15th 17th paragraph, the effective reduction of blood sugar Content. Insulin sensitivity is related to the wide range of diabetes. Treatment and increase 22. If the scope of application for patents is 15-17, C is type 2 diabetes. The use of the member, including the diabetes 23 201041587 IV. Designated representative map: (1) The representative representative of the case is: ( ). b) A brief description of the symbol of the representative figure: 5. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: