CN101249136A - Application of compound red sage root tablet in pharmacy - Google Patents

Abstract

The invention relates to a new use of compound red sage root tablet in the pharmaceutical field, the compound red sage root tablet can play a role in preventing and treating complications induced by high-level glycated hemoglobin by inhibiting the generation of the glycated hemoglobin, and can be used for preparing medicaments for preventing and inhibiting the generation of the glycated hemoglobin of diabetes and treating chronic complications induced by the glycated hemoglobin, wherein the chronic complications comprise retinopathy, cataract, atherosclerosis, myocardial infarction, cerebral apoplexy, heart failure, periodontitis and osteoporosis; can improve insulin resistance of type 2 diabetes, and inhibit development of diabetes and complications. The invention has the advantages that: the compound red sage root tablet is a Chinese patent medicine with long history and definite curative effect, has less side effect, rich resources, simple and easy preparation process and stable and controllable quality, can be used for preparing the medicine for preventing or treating chronic complications induced by the glycosylated hemoglobin of the diabetes, and has very wide market prospect.

Description

Application of Compound Danshen Tablets in Pharmaceuticals

technical field

The invention relates to the application of compound danshen tablet in the field of pharmacy.

Background technique

Compound Danshen Tablets was developed by Shanghai No. 2 Traditional Chinese Medicine Factory in 1975, and it was recorded in the 1977, 1985, 1995, 2000, and 2005 editions of the Pharmacopoeia of the People's Republic of China.

According to the records of the 2005 edition of the Pharmacopoeia, this product is composed of Danshen extract, Panax notoginseng and borneol. Among them, Salvia miltiorrhiza is bitter and slightly cold, which can promote blood circulation, unblock the veins, and remove stasis and nourish blood; The key medicine can increase coronary blood flow; borneol is pungent and cold, and it is the top grade for resuscitating the mind, clearing away heat and relieving pain. The compatibility of the above-mentioned medicines has the effects of promoting blood circulation and removing stasis, dredging the meridian and activating collaterals, regulating qi and relieving pain, refreshing and resuscitating the mind. This product is clinically used to treat chest obstruction caused by qi stagnation and blood stasis, symptoms include chest tightness, precordial tingling; coronary heart disease angina pectoris, a commonly used Chinese patent medicine. Compound Danshen Tablet has been in clinical practice for more than 30 years, and a large number of medical experiments and clinical application practices have proved that its pharmacological effects and clinical application range are far greater than the functions and indications stated in the Chinese Pharmacopoeia. The summary is as follows:

1. Compound Danshen Tablets are currently mainly found to have the following pharmacological effects

1.1 The role of dilating coronary arteries and increasing blood flow

In the article "Study on the Pharmacological Effects of Compound Danshen Tablets" (Research on Chinese Patent Medicine, 1984, (I1): 22.24), Wang Junmo and others believed that: Compound Danshen Tablets can significantly increase the coronary flow of the isolated guinea pig perfused heart, and with concentration The effect is strengthened by increasing; it also has the effect of increasing coronary flow in the perfused heart with heart failure caused by hypoxia.

1.2 Anti-myocardial ischemia effect

Pan Wenjun believed in the article "The Effect of Compound Danshen Tablets on Experimental Myocardial Infarction and Myocardial Enzyme Spectrum in Rabbits" (Journal of Shenyang Pharmaceutical University 2005, 22(1): 53-55) that: Compound Danshen Concentrated Tablets have a good inhibitory effect. Effects of myocardial infarction and improvement of myocardial enzymes in rabbits. Gao Xiumei ("Research on the Anti-Myocardial Ischemia Effect of Compound Danshen Recipe" Tianjin Traditional Chinese Medicine, 2003: (1): 23-42) used the rat model of coronary artery ligation, and used the myocardial ischemic area, myocardial enzymes, and free radicals as drugs. effectiveness indicators. To observe the anti-myocardial ischemia effect of Compound Danshen Tablets. The results showed that this product can reduce the infarct size of rats, reduce the ST segment of electrocardiogram, decrease the content of plasma LDH, and increase the content of SOD.

1.3 Antiarrhythmic effect

In the article "Study on the Pharmacological Effects of Compound Danshen Tablets" (Research on Chinese Patent Medicine, 1984, (I1): 22.24), Wang Junmo and others believed that: the compound Danshen Tablets administered to mice can significantly inhibit the chloroform-induced ventricular fibrillation in mice. , can also shorten the time of barium chloride-induced arrhythmia in rats.

1.4 Protective effect on myocardial ischemia-reperfusion injury

Zhang Yu, et al. ("Protective Effect of Compound Danshen Tablets on Myocardial Ischemia-Reperfusion Injury in Rats" Henan Journal of Traditional Chinese Medicine, 1997: 12(6): 15-17) believed that: Compound Danshen Tablets significantly shortened the rate of reperfusion in rats. The duration of arrhythmia can also reduce myocardial MDA content and increase SOD activity; suggesting that its anti-reperfusion arrhythmia effect may be related to inhibiting lipid peroxidation and reducing free radical damage. This product also significantly improved the low cardiac function caused by ischemia-reperfusion in the isolated rat heart, and the Ca2 ⁺ content in myocardial tissue was significantly reduced; suggesting that its mechanism of action may protect mitochondrial function by reducing calcium accumulation in ischemia-reperfusion myocardium And inhibit the generation of xanthine oxidase, prevent lipid peroxidation and other ways to achieve.

1.5 Mitigate the effects of antipsychotic drugs on the heart

Zhuang Jianhua believed in the article "The Effect of Compound Danshen Tablets on the Effects of Antipsychotic Drugs on the Heart" (National Medical Forum, 2000: 15(2): 40-41) that: Compound Danshen Tablets can reduce the effects of antipsychotic drugs on the heart and Toxicity, and it has a very obvious effect in improving T wave or Q-T interval prolongation caused by antipsychotic drugs.

1.6 Protective effect on cerebral ischemia

Fan Zhaodong ("Research on the Protective Effect of Compound Danshen Tablets on Experimental Cerebral Ischemia in Rats" Journal of Shanxi Staff Medical College, 2000: 10(2): 3-4) showed that Compound Danshen Tablets can reduce the cerebral Index, significantly reduce the brain water content of cerebral ischemia model rats, and significantly reduce the permeability of cerebral blood vessels, reduce cerebral edema, promote the recovery of ischemic brain tissue damage, and have obvious protective effects on ischemic brain tissue. Zhu Yonglin ("Effect of Compound Danshen Tablets on the Expression of HIF-1α in the Brain of Rats with Chronic Cerebral Ischemia" Journal of Practical Neurological Diseases 2005: 8(5): 18-19) showed that the expression of HIF-1α in the brain of rats in the treatment group Visibly enhanced. It is considered that Compound Danshen Tablets can significantly increase the expression of HIF-1α in the brain of 2VO rats, and promote the compensatory repair of chronic cerebral ischemia.

1.7 Effects on experimental thrombosis

Qu Caiqin ("Effect of Compound Danshen Tablets on Experimental Thrombosis in Rats" Hebei Traditional Chinese Medicine, 1999: 21 (4): 252) research shows that Compound Danshen Tablets significantly prolongs the time of thrombosis in rats, and the dose increases and the effect is enhanced. The author believes that: Compound Danshen Tablet has a definite preventive effect on thrombosis.

1.8 Effects on the content of amino acid neurotransmitters in the brain of Alzheimer's disease rats

In the article "The Effect of Compound Danshen Tablets on the Content of Amino Acid Neurotransmitters in the Brain of Alzheimer's Rats" (Chinese Herbal Medicine, 2004: 35 (8): 905-908), Qin Ren'an believes that: Compound Danshen Tablets can reduce excitatory amino acid Content, to resist the toxicity of excitatory amino acids, which may be one of the mechanisms of its prevention and treatment of Alzheimer's disease. At the same time, the research of Qin Ren'an "The Effect of Compound Danshen Tablets on Learning and Memory Impairment and Brain Tissue β-AP Content in Alzheimer's Disease Rats" (Chinese Journal of Traditional Chinese Medicine, 2005: 20(6): 377-378) showed that: Compound Danshen Tablets can significantly improve the learning and memory dysfunction of experimental AD rats, and can inhibit the production of β-AP in brain tissue

1.9 Anti-pulmonary fibrosis

Song Jianping ("Effects of Fufang Danshen Tablets, Shengmaiyin, and Wushe Powder on Pingyangmycin-induced Pulmonary Fibrosis Model Rats (J). Chinese Journal of Traditional Chinese Medicine, 2002: 43 (2): 142-143] used intratracheal drip The model was replicated by adding Pingyangmycin, and treated with compound Danshen tablet by gavage. The results showed that the lung coefficient, HYP content in lung tissue, alveolitis and pulmonary fibrosis were lower than those in the model control group.

2 Compound Danshen Tablets are currently mainly used to treat the following clinical diseases

2.1 Senile cardiovascular and cerebrovascular diseases

Li Zhengxi ("Observation on the Curative Effect of Compound Danshen Tablets in Treating 133 Cases of Senile Cardiovascular and Cerebrovascular Diseases" Guizhou Medicine, 1989: 13(2): 121-122) used Compound Danshen Tablets to treat 133 cases of senile cardiovascular and cerebrovascular diseases. The results showed that: Significant differences were observed in patients' electrocardiogram, cerebral blood flow diagram, liver function and blood lipid, as well as symptoms before and after treatment. It is believed that Compound Danshen Tablet has better effect on ST segment and T wave changes of subacute myocardial infarction; and the curative effect will be higher with the prolongation of the course of treatment.

2.2 Neurasthenic syndrome after traumatic brain injury

Zhang Yilu ("Compound Danshen Tablets Treating 122 Cases of Neurasthenic Syndrome after Craniocerebral Trauma", Yunnan Journal of Traditional Chinese Medicine, 1984: 5(5): 24-26) used Compound Danshen Tablets to treat 122 cases of neurasthenia syndrome after craniocerebral trauma. The efficiency reaches 90.2%. Cerebral blood flow graph indicated that the elasticity of blood vessels after treatment was better than that before treatment. It shows that Compound Danshen Tablets can increase cerebral blood flow, improve cerebral blood circulation, regulate tissue repair and regeneration, and further promote the recovery of central nervous system function.

2.3 Liver disease

2.3.1. Fatty liver

Wei Dexin believed in the article "Cloning and Compound Danshen Tablets Treating 49 Cases of Fatty Liver" (Chinese Journal of Integrated Traditional Chinese and Western Medicine 2000: 20 (10): 788-789) that: Compound Danshen Tablets can promote liver circulation and inhibit the accumulation of exogenous cholesterol. Absorption improves hepatic fat metabolism, thereby achieving the purpose of treating fatty liver.

2.3.2 Hepatitis B

Kong Wuming, Gong Jun, and Dong Lei believed in the article "The Effect of Compound Danshen Tablets Combined with Vitamin E on Hepatic Fibrosis in Chronic Hepatitis B" (Chinese Journal of Practical Internal Medicine, 2005: 25(9): 799-801) that: compound Danshen tablet combined with vitamin E has a certain blocking effect on the development of liver fibrosis, without obvious side effects. It can improve liver microcirculation, inhibit stellate cell activation and collagen formation, increase lymphocyte activity, improve liver fibrosis, and delay the pathological development of hepatitis. In addition, as a natural antioxidant, Danshen can protect the integrity and permeability of liver cell membranes and mitochondrial membranes, and one of its pharmacological effects is to scavenge cytotoxic oxygen free radicals.

3.3.3 Liver cirrhosis

Sun Quan, etc. in the article "32 cases of liver cirrhosis and ascites treated with hepatocyte growth hormone combined with compound Danshen tablet" (Journal of Integrated Traditional Chinese and Western Medicine, 1998 supplement (below): 165) believed that: the combination of hepatocyte growth hormone and compound Danshen tablet The application has a certain effect on improving microcirculation, preventing progressive necrosis of liver cells, increasing serum albumin, eliminating ascites, and restoring liver function. In the article "Gansu Granules Combined with Compound Danshen Tablets in the Treatment of 28 Cases of Liver Fibrosis" (Journal of Jiangxi University of Traditional Chinese Medicine, 2000: 12(3): 7), she believed that Gansu Granules and Salvia Miltiorrhiza have the same anti-hepatic fibrosis effect , two drugs in combination, the effect is enhanced.

2.4 Treatment of hypertension

Tan Xiao believed in the article "Clinical Analysis of Nifedipine and Compound Danshen Tablets in the Treatment of Elderly Hypertension" (Journal of Modern Medicine, 1998: 8(6): 69-70) that the combination of the two drugs can treat hypertension, coronary heart disease, and angina pectoris The effect is better, and it is especially suitable for elderly hypertensive patients with coronary heart disease, angina pectoris, and cerebrovascular disease.

In the article "Observation on the Curative Effect of Compound Danshen Tablets in Treating Convalescent Pregnancy-induced Hypertension" (Henan Journal of Practical Neurology, 2002: 5(2): 66), it is believed that the addition of compound Danshen Tablets to blood pressure-lowering drugs is effective in lowering blood pressure. , improve renal blood flow, eliminate urinary protein has a better effect, and less side effects. It is believed that Compound Danshen Tablets is a safe and effective drug in the convalescent treatment of PIH.

2.5 Other clinical applications:

Cao Yin'e used this product to treat skin pruritus in the article "Compound Danshen Tablets Treating Senile Skin Pruritus" (Shandong Medicine, 1997: 37(8): 62-63), mainly by increasing the blood supply of the skin and improving the nutritional status of the skin. Symptoms of skin itching were relieved or subsided.

Zhang Qingwen and Liu Qili believed in the article "Compound Danshen Tablets Treating Gastrointestinal Spasmodic Abdominal Pain" (Chinese Rural Medicine): Compound Danshen Tablets have the effect of calcium antagonism and improving microcirculation, thereby alleviating smooth muscle spasm abdominal pain, although the curative effect is different from that of atropine No significant, but few side effects, has clinical practical value.

In the article "Observation on the Curative Effect of Compound Danshen Tablets in Treating Colles' Fracture" (Jiaotong Medical Sciences, 1999: 13(1): 120), Li Lidong believed that on the basis of traditional methods, taking Compound Danshen Tablets for 78 patients with Cblles fractures shortened the healing time. ,Significant effect.

Ni Xiuying and Zheng Rong believed in the article "Observation on the Effect of Compound Danshen Tablets in Treating Type I Chronic Schizophrenia" (Strait Pharmacy, 2001: 13(4): 31) that it is helpful for the treatment of negative symptoms of type I chronic schizophrenia. .

In the article "New Uses of Compound Danshen Tablets" (Family Traditional Chinese Medicine), Mei Quanxi believes that this prescription can also treat: bronchial asthma; neurasthenia syndrome; dysmenorrhea; pigmented purpura skin disease; superficial scleritis; deafness in children ; Secondary epilepsy in children.

It can be seen that in addition to being mainly suitable for the prevention of cardiovascular and cerebrovascular diseases and the long-term treatment of chronic cardiovascular and cerebrovascular diseases, the scope of clinical application of Compound Danshen Tablets is gradually expanding.

Diabetes is a common metabolic endocrine disease that can cause a variety of diabetic complications, including diabetic retinopathy, diabetic cataract, diabetic skin disease, diabetic osteomyelitis, diabetic osteoarthritis, diabetic foot, etc., seriously affecting patients The harm to the human body is second only to cancer, and it is called the second killer in modern diseases. At present, there are 125 million diabetic patients in the world, and more than 300 million people in all countries are at risk of developing diabetes. The number of diabetic patients in my country has reached 40 million. For some high-end areas, the economic loss caused by diabetes may even be greater than the so-called "epidemic AIDS of the century". By 2025, 75% of people with diabetes will be in developing countries. Many people worry that urbanization and rapid cultural and social changes may be an important factor causing the increase in diabetes in developing countries. At present, diabetes tends to expand and rejuvenate, so the scope of the harmful population is increasing.

In the state of diabetes, reducing glucose and other sugars (such as fructose) can react with the ε-amino group of the side chain of amino acid residues in various proteins in the body or the α-amino group of the amino terminal to form a reversible Schiff base under non-enzymatic catalysis (several hours ), and further react to form a relatively stable but still reversible sugar-protein ketamine conjugate (several days or weeks), if it is a protein with a long half-life (such as collagen, crystal protein, elastin and nerve myelin, etc.), Then continue to undergo complex recombinant dehydrogenation to form irreversible glycation end products (AGEs). AGEs are irreversibly combined with the above-mentioned proteins in the form of covalent bonds. Even if the blood sugar is corrected, AGEs will not decrease, and will continue to accumulate with the increase of blood sugar concentration and the prolongation of the protein exposure time to glucose. It is called protein non-enzyme. saccharification. Glycosylated hemoglobin is the product of the combination of hemoglobin and blood sugar in red blood cells in human blood. The higher the glycosylated hemoglobin, the more blood sugar is combined with hemoglobin, and the diabetes is more severe. The English code name of glycosylated hemoglobin is HbA1C. Glycated hemoglobin can reflect the average level of blood sugar control in the past 2-3 months, and it is not affected by an occasional rise or fall in blood sugar. Therefore, the measurement of glycosylated hemoglobin can provide a comprehensive understanding of the blood sugar control level in the past period of time . Authoritative organizations in the world have clear control indicators for glycosylated hemoglobin. ADA (American Diabetes Association) recommends that glycosylated hemoglobin be controlled at less than 7%, and IDF (International Diabetes Federation) recommends that glycosylated hemoglobin be controlled at less than 6.5%. The control standard is set below 6.5%.

Since glycosylated hemoglobin can change the affinity of red blood cells for oxygen, it will accelerate the formation of cardiovascular and cerebrovascular complications. It can cause glomerular basement membrane thickening, induce diabetic nephropathy, and cause increased blood lipids and blood viscosity. Elevated glycosylated hemoglobin is a high-risk factor for myocardial infarction and stroke death. For every 1% increase in HbA1c, the relative risk of mortality increased by 24% in men and 28% in women. Once the glycated hemoglobin exceeds 7%, the risk of cardiovascular and cerebrovascular diseases will increase by more than 50%. Fan Quan and others from Xijing Hospital of Fourth Military Medical University found that the level of glycosylated hemoglobin is positively correlated with the degree of coronary artery disease, and is an independent risk factor for coronary heart disease. The study found that the elevated index of glycosylated hemoglobin in the simple coronary heart disease group, coronary heart disease combined with impaired glucose tolerance group, and coronary heart disease combined with type 2 diabetes group was 4.5%, 6.7% and 12.5%, respectively, and the difference was significant; the coronary artery stenosis score was 5.8 points, 7.4 points and 14.5 points, the difference is significant. The level of glycosylated hemoglobin was positively correlated with the score of coronary artery disease. The results of this study suggest that lowering the level of glycosylated hemoglobin has important clinical significance in preventing and delaying the occurrence and development of atherosclerosis and cardiovascular complications. A British prospective study confirmed that for every 1% reduction in glycated hemoglobin, diabetes-related mortality is reduced by 21%; the incidence of myocardial infarction is reduced by 14%; the incidence of stroke is reduced by 12%; the incidence of microvascular disease is reduced by 37%; cataract extraction is reduced by 19% %; amputation or death due to peripheral vascular disease decreased by 43%; the incidence of heart failure decreased by 16%.

It has also been reported that diabetes patients with a HbA1c value higher than 8% are likely to develop secondary osteoporosis; HbA1c is highly correlated with periodontal indicators, especially attachment loss (AL), and through effective control of HbAlc, AL tends to Get better and lay a good foundation for periodontal treatment. Therefore, glycosylated hemoglobin is a very important monitoring indicator for diabetic patients, and its level directly determines the occurrence and development of various chronic complications that seriously affect the quality of life of diabetic patients in the future.

At present, it is generally recognized in the academic circles that the prevention and treatment of chronic complications of diabetes is mainly through the two classic ways of inhibiting the activity of aldose reductase and reducing the end products of glycation (see "Chronic Complications of Diabetes", edited by Shen Zhizhou, Wu Songhua, Shao Fuyuan, Chen Guohui, Shanghai Medical University Press, 1999 January 1st edition of "Clinical Diabetes" edited by Ye Shandong Zhu Xixing Anhui Science and Technology Press October 2005 1st edition). For example, aminoguanidine is a kind of nucleophilic hydrazine compound, which can react with the intermediate product 3-deoxyglucosone aldehyde and the early product of the glycosylation reaction, and block the non-enzymatic early glycosylation product of the protein from further forming the glycosylation end product, obviously preventing The occurrence and development of various chronic complications of diabetes may also be partly related to the inhibition of protein non-enzymatic glycation and the reduction of free radical formation. In addition, aminoguanidine can also inhibit the oxidation of lipids and fatty acids. However, there is no report on the therapeutic effect of aminoguanidine on chronic complications of clinical diabetic patients, and its clinical efficacy and adverse reactions are yet to be evaluated.

Insulin is the only hypoglycemic hormone in the body secreted by the β cells of the human pancreas. Insulin resistance refers to the decreased sensitivity of the peripheral tissues in the body to insulin, the insensitivity of tissues to insulin, and the resistance of peripheral tissues such as muscle and fat to the role of insulin in promoting glucose uptake, so that insulin cannot normally play the function of lowering blood sugar. A large number of epidemiological data show that insulin resistance is an important reason for the development of diabetes, hypertension, hyperlipidemia and other diseases. Studies have found that insulin resistance is common in type 2 diabetes, accounting for almost 90%, and may be one of the main factors of type 2 diabetes. Therefore, the drug treatment of diabetes should be aimed at its etiology, focusing on improving insulin resistance and protecting the function of pancreatic β cells. Drugs that can improve insulin resistance must be selected. These drugs are mainly insulin sensitizers. Insulin sensitizers can increase the body's sensitivity to its own insulin, so that its own insulin can be "resurrected" and fully play its role, so that blood sugar can be re-absorbed by the body's tissue cells and Utilize it to reduce blood sugar, achieve long-term stable and comprehensive control of blood sugar, enable the human body to enjoy the insulin secreted by itself for a long time, enable diabetic patients to receive timely, effective and fundamental treatment, and prevent the occurrence and development of chronic complications of diabetes.

Modern medical research shows that insulin resistance seems to be at the core of many risk factors for cardiovascular diseases, or that insulin resistance is a common risk factor for many diseases, especially diabetes and cardiovascular diseases, and is the cause of many metabolic related diseases. common soil. In recent years, the pathogenesis of type 2 diabetes has made remarkable progress. Insulin resistance and B cell secretion defects are the two main links in its pathogenesis. B cells can still compensate for insulin resistance by increasing insulin secretion and maintain blood sugar at Relatively low levels, improve glucose tolerance and insulin tolerance, thereby inhibiting the development of diabetic complications.

Contents of the invention

The purpose of the present invention is to provide a new application of the compound danshen tablet, that is, a new application in pharmacy.

Actually, the present invention relates to the application of Compound Danshen Tablets in the preparation of medicines for preventing or inhibiting the formation of glycated hemoglobin in diabetes.

The invention relates to the application of compound danshen tablet in the preparation of medicaments for preventing or treating diabetic glycosylated hemoglobin-induced retinopathy.

The invention relates to the application of compound danshen tablet in the preparation of medicaments for preventing or treating diabetic glycosylated hemoglobin-induced cataract.

The invention relates to the application of compound Danshen tablets in the preparation of drugs for preventing or treating atherosclerosis induced by glycated hemoglobin in diabetes.

The invention relates to the application of compound danshen tablet in the preparation of medicines for preventing or treating diabetic glycated hemoglobin-induced myocardial infarction.

The invention relates to the application of compound danshen tablet in the preparation of a medicament for preventing or treating stroke induced by diabetic glycated hemoglobin.

The invention relates to the application of compound Danshen tablets in the preparation of medicines for preventing or treating heart failure induced by diabetic glycated hemoglobin.

The invention relates to the application of compound danshen tablet in the preparation of medicaments for preventing or treating diabetic glycated hemoglobin-induced periodontitis.

The invention relates to the application of compound danshen tablet in the preparation of medicaments for preventing or treating osteoporosis induced by diabetic glycated hemoglobin.

It relates to the application of compound Danshen tablet in the preparation of medicine for improving insulin resistance of type 2 diabetes.

Compound Danshen Tablets can inhibit the formation of glycosylated hemoglobin, the end product of glycation, and can be used to prevent and inhibit the formation of glycosylated hemoglobin in diabetes and the generation of chronic complications induced by it, including retinopathy, cataract, arterial Atherosclerosis, myocardial infarction, stroke, heart failure, periodontitis, osteoporosis; at the same time, Compound Danshen Tablets can improve insulin resistance in type 2 diabetes, thereby inhibiting the development of type 2 diabetes and the occurrence of complications.

In order to better understand the essence of the present invention, the application of Compound Danshen Tablets in pharmacy will be further illustrated below through experimental examples. Compound Danshen Tablets according to the present invention are used to prevent and inhibit the formation of glycated hemoglobin in diabetes and treat chronic complications induced by it and improve insulin resistance, insulin tolerance and glucose tolerance of type 2 diabetes according to the methods shown in the following examples Research. The methods involved are technical means that can be grasped and used by those skilled in the art, but the following implementation examples shall not be construed as limiting the claims of the present invention in any sense.

Implementation Example 1: Effect on Formation of Glycated Hemoglobin in Diabetic Rats

1. Experimental materials.

1. Drugs and reagents:

Compound Danshen Tablets, batch number: B7A008, Guangzhou Baiyunshan Hutchison Huangpu Traditional Chinese Medicine Co., Ltd., made into powder, dissolved in distilled water; adult dosage is 9 capsules/day, equivalent to 5.4g crude drug/day; The high and high doses are respectively 3.5, 7, and 14 times (calculated by body weight) of the human clinical administration dose, that is, about 0.3, 0.6, and 1.2 g crude drug/kg respectively.

Aminoguanidine (aminoguanidine, AG), streptozotocin (streptozotocin, STZ), Sigma company, before use, be made into a 1% STZ solution with a citric acid buffer;

Blood glucose test strips, provided by Roche Pharmaceuticals, Switzerland (lot number: 449497);

Glycosylated hemoglobin assay kit (batch number: 20070621), provided by Nanjing Jiancheng Bioengineering Institute.

2. Instrument:

Refrigerated centrifuge (J268 type): Beckman company;

Spectrophotometer (type 752): Shanghai Third Analytical Instrument Factory;

High-speed refrigerated centrifuge: eppendorfCentrifuge5417R;

Fluorescence spectrophotometer (F24000): Hitachi, Japan;

Micro shaker (MM22 type): Shanghai Xianghua Chemical Co., Ltd.

3. Experimental animals:

Clean grade Sprague-Dawley (SD) rats were provided by Guangdong Medical Experimental Animal Center.

Second, the experimental method.

1. Establishment and grouping of diabetic rat models.

Ten rats were randomly selected as the normal control group and fed with common feed. All the other rats were used as the model group, and the rats in the model group were fed with high-fat feed (1% cholesterol, 10% lard, 10% egg yolk powder, 2% sucrose, 77% basal feed), and the animals in the model group were fasted after 4 weeks. Food (without water) overnight, intraperitoneal injection of STZ solution 30mg/kg in citrate buffer (PH4.4). The normal control group was intraperitoneally injected with the same volume of citrate buffer. After 3 days, they were fasted overnight, and blood was taken from the tail vein to measure blood glucose. Whole blood glucose ≥ 11mmol/L, urine glucose +++~++++, maintained for more than 1 week was determined as a diabetic model.

2. Dosing in groups.

The diabetic rats were divided into 5 groups, namely the model group, the aminoguanidine administration group, and the high, medium and low dose groups of Compound Danshen Tablets, with 8 rats in each group, and the animals in the groups and in the groups were marked respectively. The normal control group was given normal feed and drinking tap water, and the other groups were given high-fat sugar-free feed and drinking cold boiled water. The doses of each administration group are shown in the table below. The model control group and the normal control group were fed with equal volume of distilled water once a day for 12 consecutive weeks. 2 weeks after the administration, the urine sugar of the animals was monitored every day, and the animals with urine sugar ++++ and emaciation were subcutaneously injected with insulin 0.5u/kg every day. Animal body weights were recorded weekly. After the 12th week of the experiment, the animals were fasted for 12 hours, anesthetized by intraperitoneal injection of urethane, weighed and recorded, and blood was collected from the eyes.

3. Detection indicators.

Blood glucose, glycosylated hemoglobin (using SPSS11.0 for data analysis. The data are all expressed as mean ± standard deviation ( ±s) means. One-way analysis of variance and t test were used for each index; Kruskal-Wallis H test and g test were used for data with uneven variance. ). The test results are shown in Table 1:

±s)Table 1 The levels of blood sugar and glycosylated hemoglobin in diabetic rats of different administration groups (

±s)

group Dosage (g/kg) Blood sugar (mmol/l) Glycosylated hemoglobin (mmol/mol) Normal group Model group Aminoguanidine Hydrochloride Compound Danshen Tablets Low Dose Compound Danshen Tablets Medium Dose Compound Danshen Tablets High Dose --0.10.30.61.2 6.0±1.118.1±5.6**16.2±5.915.5±6.514.4±4.512.9±5.5# 12.1±3.1121.7±3.81**17.0±3.62#18.2±2.8617.2±2.11#16.4±2.52#

Note: Compared with the blank group, *p<0.05, **p<0.01; compared with the model group: #p<0.05, ##p<0.01.

It can be seen from the above table that compared with the normal group, the levels of blood sugar and plasma glycosylated hemoglobin of the diabetic rats in the model group were significantly higher than those of the normal group (p<0.01), suggesting that the model was modeled with streptozotocin and high-fat diet. Diabetic rats have elevated blood sugar and increased glycated products. Compared with the model group, the level of glycosylated hemoglobin in the aminoguanidine administration group decreased (p<0.05), suggesting that aminoguanidine can reduce the production of glycosylation products in diabetic rats; The levels of glycosylated hemoglobin decreased in different degrees (p<0.05), suggesting that Compound Danshen Tablet has the effect of reducing glycation products in diabetic rats, and the effect of high-dose group is the most obvious. The results suggest that Compound Danshen Tablets can prevent and treat complications induced by high levels of glycosylated hemoglobin by inhibiting the formation of glycosylated hemoglobin.

Implementation Example 2: Effects on Glucose Tolerance, Insulin Tolerance, and Insulin Sensitivity Index in Type 2 Diabetic Rats

1. Experimental materials

1 Drugs and reagents:

Compound Danshen tablets, batch number: B7A008, were purchased from Guangzhou Baiyunshan Hutchison Huangpu Traditional Chinese Medicine Co., Ltd. During the test, it was ground into powder with a mortar and dissolved in distilled water; the dosage for adults was 9 capsules/day, which was equivalent to 5.4g of crude drug/day; About 0.9g crude drug/kg.

Dameikang, Tianjin Huajin Pharmaceutical Factory, batch number: 070813.

Streptozotocin (STZ), Sigma Company, was formulated with citric acid buffer solution to a concentration of 3% STZ solution before use.

Luokang blood glucose meter and blood glucose test strips are provided by Swiss Roche Pharmaceutical Company (batch number: 449497).

The insulin kit was provided by Beijing Kemei Dongya Biotechnology Co., Ltd., batch number: 20071025.

Novolin, batch number: SVG0426, produced by Novo Nordisk, Denmark.

2. Experimental equipment.

The SN-695B intelligent radio-immunity measuring instrument is produced by the Rihuan No. 1 Factory of the Shanghai Institute of Nuclear Research.

3. Experimental animals.

Clean grade Sprague-Dawley (SD) ♂ rats were provided by Guangdong Medical Experimental Animal Center.

Second, the experimental method.

1. Establishment and grouping of diabetic rat models

Six rats were randomly selected as the normal control group and fed with common feed. All the other rats were used as the model group, and the rats in the model group were fed with high-fat feed (1% cholesterol, 10% lard, 10% egg yolk powder, 10% sucrose, 69% basal feed), and the animals in the model group were fasted after 4 weeks. Food (without water) overnight, intraperitoneal injection of STZ solution 30mg/kg in citrate buffer (PH4.4). The normal control group was intraperitoneally injected with the same volume of citrate buffer. After 3 days, they were fasted overnight, and blood was collected from the tail vein to measure blood glucose. Whole blood glucose ≥ 11mmol/L, urine glucose +++~++++, maintained for more than 1 week was determined as a diabetic model.

2. Dosing in groups.

The diabetic rats were divided into three groups, namely the model group, the Dameikang administration group and the compound Danshen tablet group, with 10 rats in each group, and the questions of the groups and the animals in the groups were marked respectively. The normal control group was given normal feed, and the other groups were given high-fat and high-sugar feed. The dosage of each administration group is shown in the table below. The model control group and the normal control group were fed with equal volume of distilled water once a day for 4 consecutive weeks.

3. Detection indicators.

(1) Changes in blood sugar, insulin, and insulin sensitivity index before and after administration

Before administration and 2 weeks after administration, animals were fasted for 12 hours, anesthetized by intraperitoneal injection of urethane, eyeball blood was collected, serum was separated, blood glucose (FBG) and insulin levels (INS) were measured before and after administration, and insulin sensitivity index (ISI) was calculated . The results are shown in Table 2 and Table 3.

±s)The content of blood sugar before and after administration of different administration groups diabetic rats of table 2 (

±s)

group Dosage (g/kg) FBG(mmol/l) before administration   2 weeks after administration Normal group model group Damei Fufang Danshen Tablets --0.050.9 5.27±0.3319.56±2.6218.77±2.5519.80±8.12 5.70±0.2120.97±7.9918.53±3.8112.32±0.91**

Note: *p<0.05, **p<0.01 after administration compared with before administration. (Test method: Paired T-Test)

As can be seen from Table 2, the level of fasting blood sugar in the normal group rats before and after treatment was basically unchanged; the blood sugar in the model group after treatment was slightly higher than before treatment, but there was no statistical difference (p>0.05); There was no significant change in blood glucose before and after treatment in the treatment group; the blood glucose in the compound Danshen Tablets administration group decreased after treatment, and there was a very significant difference (p<0.01). It suggested that Compound Danshen Tablets could improve the islet function of type 2 diabetic rats and reduce the level of fasting blood glucose.

Table 3 Changes of insulin and insulin sensitivity index before and after administration of diabetic rats in different administration groups ( ±s)

group INS(pmol/L) Lg(ISI) before administration 2 weeks after administration before administration 2 weeks after administration Normal group model group Damei Fufang Danshen Tablets 157.43±96.5877.84±29.5491.78±56.7798.64±72.83 146.86±93.3590.08±28.3866.88±26.3270.76±21.12 -2.86±0.25-3.15±0.17-3.18±0.21-3.11±0.27 -2.85±0.26-3.23±0.20-3.06±0.18*-2.91±0.16*

Note: *p<0.05, **p<0.01 after administration compared with before administration. (Test method: Wilcoxon Signed Rank Test)

It can be seen from Table 3 that the fasting insulin level of rats in the normal group decreased slightly before and after treatment, without statistical difference (p>0.05), and the insulin sensitivity index remained unchanged; The index decreased, and there was no statistical difference (p>0.05); the fasting insulin level of Dameikang administration group decreased before and after treatment, and there was no statistical difference (p>0.05), while the insulin sensitivity index increased, there was statistical difference (p <0.05); the fasting insulin level of the compound Danshen tablet administration group decreased after treatment, without statistical difference (p>0.05), but the insulin sensitivity index increased, with statistical difference (p<0.05). Tips: Compound Danshen Tablets can reduce insulin levels and blood sugar in type 2 diabetic rats to a certain extent, that is, improve insulin resistance and insulin sensitivity index.

Detailed ways

Example 1:

Take 450 grams of Salvia miltiorrhiza, add ethanol and heat to reflux for 1.5 hours, filter the extract, recover ethanol from the filtrate and concentrate to an appropriate amount, and set aside; add 50% ethanol to the dregs and heat to reflux for 1.5 hours, filter the extract, recover ethanol from the filtrate and concentrate to an appropriate amount, Standby; decoct the medicinal dregs with water for 2 hours, filter the decoction, concentrate the filtrate to an appropriate amount, crush 141 grams of Panax notoginseng into fine powder, make granules with the above concentrated solution and appropriate amount of auxiliary materials, and dry; grind 8 grams of borneol into fine powder, and mix with The above granules are mixed evenly, pressed into 1000 tablets, coated with sugar or film, and the product is ready.

Example 2:

Take the compound Danshen tablet in Example 1, take 2 to 6 tablets with warm water before or after meals, and take 1 to 4 times a day to inhibit the formation of glycosylated hemoglobin in diabetes.

Example 3:

Take the compound Danshen tablet in Example 1, take 2 to 8 tablets with warm water before or after meals, and take 1 to 4 times a day to improve insulin resistance in type 2 diabetes.

Claims (10)

1. Application of Compound Danshen Tablets in the preparation of drugs for preventing or inhibiting the formation of glycated hemoglobin in diabetes. 2. Application of Compound Danshen Tablets in the preparation of medicines for preventing or inhibiting diabetic glycosylated hemoglobin-induced retinopathy. 3. Application of Compound Danshen Tablets in the preparation of medicaments for preventing or inhibiting diabetic glycosylated hemoglobin-induced cataracts. 4. Application of Compound Danshen Tablets in the preparation of drugs for preventing or inhibiting atherosclerosis induced by glycated hemoglobin in diabetes. 5. Application of Compound Danshen Tablets in the preparation of drugs for preventing or inhibiting diabetic glycosylated hemoglobin-induced myocardial infarction. 6. Application of Compound Danshen Tablets in the preparation of medicines for preventing or inhibiting stroke induced by diabetic glycated hemoglobin. 7. Application of Compound Danshen Tablets in the preparation of drugs for preventing or inhibiting heart failure induced by diabetic glycated hemoglobin. 8. Application of Compound Danshen Tablets in the preparation of medicines for preventing or inhibiting periodontitis induced by diabetic glycated hemoglobin. 9. Application of Compound Danshen Tablets in the preparation of medicaments for preventing or inhibiting osteoporosis induced by diabetic glycated hemoglobin. 10. Application of Compound Danshen Tablets in the preparation of drugs for improving insulin resistance in type 2 diabetes.