CN101380353B - Pharmaceutical composition for preventing and curing 2-type diabetes and preparation method thereof - Google Patents
Pharmaceutical composition for preventing and curing 2-type diabetes and preparation method thereof Download PDFInfo
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- CN101380353B CN101380353B CN2008102184589A CN200810218458A CN101380353B CN 101380353 B CN101380353 B CN 101380353B CN 2008102184589 A CN2008102184589 A CN 2008102184589A CN 200810218458 A CN200810218458 A CN 200810218458A CN 101380353 B CN101380353 B CN 101380353B
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Abstract
The invention provides a pharmaceutical composition for preventing and treating type II diabetes and a preparation method thereof. The pharmaceutical composition for preventing and treating the type II diabetes is composed of pharmaceutical raw materials of 40-50 parts by weight of total flavonoids of kudzuvine root and 20-25 parts by weight of total saponins of membranous milkvetch root. The pharmaceutical composition has the effects of benefiting qi, nourishing yin, promoting fluid production and quenching thirsty, the pharmacological studies show that the pharmaceutical composition has the roles of reducing blood sugar, improving glucose tolerance, reducing urine volume, suppressing insulin resistance, lowering lipids and reducing body weight, and the pharmaceutical composition can be used for preventing and treating the type II diabetes.
Description
Technical field
The present invention relates to a kind of Chinese medicine composition, relate in particular to the drug regimen of a kind of prevention and treatment type 2 diabetes mellitus.
Background technology
Diabetes (Diabetes Mellitus; Abbreviation DM) is often referred to type 2 diabetes mellitus (T2DM); Account for more than 90% of DM sum; Be a kind of common, the multiple not normal property of endocrine metabolism disease, classified as the disease of the third-largest class serious threat human health after being only second to cardiovascular disease and tumor in developed country.Its clinical manifestation is the metabolism disorder syndrome, like " three-many-one-little " promptly: polyuria, polydipsia, polyphagia and lose weight.Severe complications can appear in the diabetes later stage; Show as infection, diabetic nephropathy, diabetic renal papillary necrosis, cataract, neuropathy and ketoacidosis etc. more; Its to the harm of human body considerably beyond diabetes itself, so diabetes are otherwise known as " sources of all kinds of diseases and ailments ".Along with the raising of China's living standards of the people, the change of life style and the aged increase, and the onset diabetes rate is just with 0.1% speed cumulative year after year.The prevalence of China's diabetes is 2%-3% at present, and the patient surpasses 3,000 ten thousand, also has a considerable amount of impaired glucose tolerance patients in addition.With diabetes directly or indirectly relevant medical expense account for the 2%-6% of whole country health care expense, all be very big burden to individual and country.Therefore most important to the treatment of diabetes and complication thereof.
Present oral antidiabetic thing; Mainly contain the effect of stimulating insulin secretion (like sulfonylurea) and strengthen sugared utilization (like the biguanides) hypoglycemic drug of periphery, also have euglycemic agent, glycosidase inhibitor, aldose reduction inhibitor agent and glycated protein inhibitor etc. in addition.Yet clinical used or be about to the hypoglycemic medicine used from present, various Western medicine all have certain limitation and untoward reaction, and like insulin resistant, hypoglycemia, lactic acidosis, life-time service leads to complications etc.Therefore, this provides a space for the Chinese medicine diabetes.Diabetes and complication thereof focus on prevention, and most of Chinese medicine blood sugar lowering have the characteristics of comprehensive function, so the medicine that blood sugar lowering can be prevented and treated simultaneously complication again is optimal selection.
TCM treatment of diabetes historical of long standing and well established, the traditional Chinese medical science be polydipsia, polyphagia, polyuria, and of a specified duration then health is become thin or urinated and pleasantly sweetly is called " quenching one's thirst " for one type of disease of cardinal symptom.The traditional Chinese medical science thinks that the main pathogenesis of diabetes is an intense heat due to deficiency of YIN, deficiency of both QI and YIN, and its rule of treatment is mainly nourishing YIN and clearing away heat, and supplementing QI and nourishing YIN is paid attention to the kidney invigorating, spleen invigorating and blood circulation promoting and blood stasis dispelling etc.Though herbal medicine efficacy is learned and clinical research shows, the hypoglycemic activity of most Chinese medicines is obvious not as chemicals, and onset is also slower, and Chinese medicine can be brought into play integrally-regulated advantage according to after the above-mentioned rule of treatment prescription, plays the therapeutical effect of giving consideration to both the incidental and fundamental.The Chinese patent medicine of existing clinically tens of kinds of treatment flu comes out, like diabetes pill, JIANGTANGSHU, YUQUAN WAN, blood sugar lowering first sheet, LIUWEI DIHUANG WAN, SHENQI JIANGTANG sheet, quench one's thirst clever sheet, JINQI JIANGTANG PIAN etc.Defectives such as though above-mentioned Chinese patent medicine has certain curative effect to diabetes and chronic complicating diseases thereof, and ubiquity is with low content of technology, dosage form is backward, dose is big, bioavailability is low, onset is slow, curative effect is understable.
Summary of the invention
To the problem that prior art exists, the objective of the invention is to overcome the weak point of above-mentioned prior art, a kind of drug regimen and method for preparing that is used to prevent and treat type 2 diabetes mellitus is provided.
The present invention adopt have blood sugar lowering, improve insulin resistant, the Radix Puerariae total flavones of blood fat reducing, blood pressure lowering effect and Radix Astragali total saponins be as main component, processes peroral dosage form.Radix Puerariae total flavones is the total flavonoids substance of extraction separation from the legume pueraria lobata root, and main component is puerarin, daiazi, daidzein etc.Modern pharmacological research shows that Radix Puerariae total flavones has effects such as blood sugar lowering, blood fat reducing, analgesic, resisting myocardial ischemia.Process the puerarin injection medicine at present and be widely used in treatment coronary heart disease, angina pectoris etc. clinically.Radix Astragali total saponins is the total saponins class material of extraction separation from the leguminous plant Radix Astragali, and main component is an astragaloside etc.Pharmacological research shows that Radix Astragali total saponins has blood sugar lowering, enhancing human body immunity power and to cardiovascular protection effect etc.Process Radix Astragali injection at present and be widely used in treatment diabetes, diabetic nephropathy, coronary heart disease etc. clinically.At present, in the clinical practice, Radix Astragali injection and puerarin injection are often united use, are used to treat cardiovascular disease such as diabetes, coronary heart disease, angina pectoris, and effect is remarkable, and be more effective with Radix Astragali injection or puerarin injection than single.Therefore, Radix Puerariae total flavones and the application of Radix Astragali total saponins compatibility had synergism.
For reaching above-mentioned purpose, the drug regimen of control type 2 diabetes mellitus of the present invention, the technical scheme below adopting:
A kind of drug regimen of preventing and treating type 2 diabetes mellitus is made up of following materials of weight proportions medicine: 40～50 parts of Radix Puerariae total flavoness, 20～25 parts of Radix Astragali total saponinss.
Further, the weight proportion of crude drug of the present invention is preferably: 50 parts of Radix Puerariae total flavoness, 25 parts of Radix Astragali total saponinss;
Further, said pharmaceutical composition and extract or refining thing can add conventional adjuvant or excipient, process clinical acceptable forms, are peroral dosage form; Peroral dosage form is selected from a kind of in the middle of the pill, tablet, capsule;
Above-mentioned pharmaceutical composition is applied in the endocrine system disease aspect, is used for type 2 diabetes mellitus prevention and treatment.
The source of crude drug of the present invention is: Radix Puerariae total flavones is the extract of the dry rhizome of legume pueraria lobata Pueraria Iobata Ohwi or Pachyrhizua angulatus (Pueraria thomsonii Benth) through ethanol extraction, purification by macroporous resin gained.Radix Astragali total saponins is the extract of the dry root of leguminous plant Radix Astagali Astragalus membranaceus (Fisch.) Bunge var.mongholicus (Bunge) H siao or Radix Astragali A.membranaceus (Fisch.) Bunge through ethanol extraction, purification by macroporous resin gained.Quality standard: one one of Pharmacopoeia of the People's Republic of China version in 2005.
A kind of method for preparing of preventing and treating the drug regimen of type 2 diabetes mellitus comprises the steps:
1., at first prepare Radix Puerariae total flavones, get Radix Puerariae crude drug decoction pieces, add 12 times of amount 80% alcohol heating reflux 2 times, each 2 hours, filter medicinal residues, merging filtrate, gained filtrating is carried out decompression recycling ethanol and is made medicinal liquid; AB-8 macroporous resin adsorption on the above-mentioned medicinal liquid, last appearance concentration is 0.1g crude drug/ml, applied sample amount is 10BV, flow velocity 1ml/min, preadsorption 2 hours heavily adsorbs 2 times, adsorption site is washed to there not being reducing sugar reaction again; Adsorption site carries out 50% ethanol 10BV volume and carries out eluting, and flow velocity is 2ml/min, and decompression recycling ethanol liquid is ground into 14 order granules with pulverizer after the lyophilization, and total flavones purity 60% is subsequent use;
2., the preparation Radix Astragali total saponins, get Radix Astragali decoction pieces and add 10 times of amount 60% alcohol heating reflux 2 times, each 2 hours, filter medicinal residues, merging filtrate, gained filtrating is carried out decompression recycling ethanol and is made medicinal liquid; AB-8 macroporous resin adsorption on the above-mentioned medicinal liquid, last appearance concentration is 0.1g crude drug/ml, applied sample amount is 10BV, flow velocity 1ml/min, preadsorption 2 hours heavily adsorbs 2 times, adsorption site is washed to there not being reducing sugar reaction again; Adsorption site is with 0.5% sodium hydroxide (NaOH) eluting, and flow velocity is 2ml/min, continues to be washed till neutrality with 10% ethanol; Reuse 80% ethanol 10BV volume eluting, flow velocity is 2ml/min, decompression recycling ethanol liquid; Be ground into 14 order granules with pulverizer after the lyophilization, total saponins purity 60%, subsequent use;
3., the Radix Puerariae total flavones with above-mentioned preparation, Radix Astragali total saponins, press each composition weight proportion of drug regimen: 40～50 parts of Radix Puerariae total flavoness, 20～25 parts of Radix Astragali total saponinss, above material mixing stirs, and makes drug regimen then.
The present invention is a kind of supplementing QI and nourishing YIN that has, and the drug regimen of promoting the production of body fluid to quench thirst effect, pharmacological research show that it has blood sugar lowering, improves carbohydrate tolerance, reduces the urine amount, suppresses the effect of insulin resistant, lowering blood-fat and reducing weight.And, this drug regimen blood sugar lowering, improve carbohydrate tolerance, to suppress the insulin resistant effect all eager to excel in whatever one does with Radix Puerariae total flavones, Radix Astragali saponin than independent.Can be used for the prevention and the treatment of type 2 diabetes mellitus.
Description of drawings
Fig. 1 is the process chart that the present invention prepares Radix Puerariae total flavones;
Fig. 2 is the process chart that the present invention prepares Radix Astragali total saponins.
The specific embodiment
For further understanding characteristic of the present invention, technological means and the specific purposes that reached, function, will describe in further detail the present invention through zoopery below.
Drug regimen of the present invention, the materials of weight proportions medicine is formed: 40～50 parts of Radix Puerariae total flavoness, 20～25 parts of Radix Astragali total saponinss; Each composition weight proportion is preferably: 50 parts of Radix Puerariae total flavoness, 25 parts of Radix Astragali total saponinss.Pharmaceutical composition of the present invention is applied in the endocrine system disease aspect; Be used for the prevention and the treatment of type 2 diabetes mellitus; This pharmaceutical composition and extract or refining thing can add conventional adjuvant or excipient; Process clinical acceptable forms, be peroral dosage form, peroral dosage form is selected from a kind of in the middle of the pill, tablet, capsule.
The method for preparing of drug regimen of the present invention comprises the steps:
1., at first prepare Radix Puerariae total flavones, get Radix Puerariae crude drug decoction pieces, add 12 times of amount 80% alcohol heating reflux 2 times, each 2 hours, filter medicinal residues, merging filtrate, gained filtrating is carried out decompression recycling ethanol and is made medicinal liquid; AB-8 macroporous resin adsorption on the above-mentioned medicinal liquid, last appearance concentration is 0.1g crude drug/ml, applied sample amount is 10BV, flow velocity 1ml/min, preadsorption 2 hours heavily adsorbs 2 times, adsorption site is washed to there not being reducing sugar reaction again; Adsorption site carries out 50% ethanol 10BV volume and carries out eluting, and flow velocity is 2ml/min, and decompression recycling ethanol liquid is ground into 14 order granules with pulverizer after the lyophilization, and total flavones purity 60% is subsequent use;
2., the preparation Radix Astragali total saponins, get Radix Astragali decoction pieces and add 10 times of amount 60% alcohol heating reflux 2 times, each 2 hours, filter medicinal residues, merging filtrate, gained filtrating is carried out decompression recycling ethanol and is made medicinal liquid; AB-8 macroporous resin adsorption on the above-mentioned medicinal liquid, last appearance concentration is 0.1g crude drug/ml, applied sample amount is 10BV, flow velocity 1ml/min, preadsorption 2 hours heavily adsorbs 2 times, adsorption site is washed to there not being reducing sugar reaction again; Adsorption site is with 0.5% sodium hydroxide (NaOH) eluting, and flow velocity is 2ml/min, continues to be washed till neutrality with 10% ethanol; Reuse 80% ethanol 10BV volume eluting, flow velocity is 2ml/min, decompression recycling ethanol liquid; Be ground into 14 order granules with pulverizer after the lyophilization, total saponins purity 60%, subsequent use;
3., the Radix Puerariae total flavones with above-mentioned preparation, Radix Astragali total saponins, press each composition weight proportion of drug regimen: 40～50 parts of Radix Puerariae total flavoness, 20～25 parts of Radix Astragali total saponinss, above material mixing stirs, and makes drug regimen then.
Example 1 (hard capsule):
Get 50g Radix Puerariae total flavones, 25g Radix Astragali total saponins, add the 100g dextrin, add starch to 250g, mixing sprays 40% ethanol moistening, processes granule, and is dry below 60 ℃, sieves, and the capsule of packing into No. 1 is processed 1000 of hard capsules (0.25g/ grain).Taking dose is: every day 2 times, each 2.
Example 2 (tablets):
Get 50g Radix Puerariae total flavones, 25g Radix Astragali total saponins, add the 100g dextrin, add starch to 200g, mixing is processed granule, and is dry below 60 ℃, is pressed into 1000 (0.20g/ sheets), and the bag film-coat promptly gets.Taking dose is: every day 2 times, each 2.
Example 3 (granules):
Get 50g Radix Puerariae total flavones, 25g Radix Astragali total saponins, with adding the 100g dextrin, add starch to 250g, mixing is processed granule, and is dry below 60 ℃, is distributed into 500 bags (0.5g/ bags).Taking dose is: every day 2 times, each 1 bag.
Below be the technique effect that the present invention of zoopery proof has:
One, the medicine efficacy screening experiment of the drug regimen hypoglycemic activity of control type 2 diabetes mellitus
1 material:
1.1 animal: the KM mice, male, body weight (20 ± 2) g, SPF level.
1.2 reagent and instrument:
Receive the reagent thing: drug regimen of the present invention (contains Radix Puerariae total flavones 50g, purity 60%; Radix Astragali total saponins 25g, purity 60%), Radix Puerariae total flavones, purity 60%; Radix Astragali total saponins, purity 60%; Provide by Traditional Chinese Medicine University Of Guangzhou new drug development research center; Positive control drug: glyburide (glimepiride), specification: 4mg/ sheet, Yangtze River Pharmaceutical are produced, and lot number 080104 faces with preceding grinding and is mixed with 0.1mg/ml solution with distilled water; Glucose, citric acid, sodium citrate are analytical pure; Streptozotocin (STZ), U.S. sigma company produces; The blood glucose test kit; ELIASA.
2 experimental techniques
Dosage converts: medicine centering, the ratio of the Radix Puerariae and the Radix Astragali are 1: 1 (Radix Puerariae 30g, Radix Astragali 30g).Investigate according to medical material, content of total flavone is 40.0mg/g in the used medical material Radix Puerariae, and total saponin content is 20mg/g in the Radix Astragali.According to 100% rate of transform and extract purity; Clinical equivalent dosage according to people's per kilogram of body weight (60kg) conversion mice is respectively: Pueraria lobota ketone (Radix Puerariae total flavones) is 335mg/kg; Xanthosine (Radix Astragali total saponins) is 165mg/kg, and Pueraria lobota-yellow effective site is 500mg/kg (Radix Puerariae total flavones is 165mg/kg for the 335mg/kg+ Radix Astragali total saponins).
Get about 180 of KM kind mice, the adaptability of entering the room was raised 2 days, got 16 as the normal control group; All the other mice fasting 12h, in next day lumbar injection STZ160mg/kg (STZ is by citric acid buffer salt preparation, and pH value is 4.4; Face and use preceding preparation), behind the 72h, mice fasting 12h; Get blood with capillary glass-tube eyeground vein clump, and measure FBG (fasting glucose), selecting the mice of FBG >=11.1mmol/L is diabetic mice; Animal is divided into 10 groups at random, 16 every group, is respectively model group and each drug group (seeing table 3).Each treated animal gastric infusion, every day 1 time, continuous 15 days, after the last administration, animal fasting 12h detected carbohydrate tolerance (OGTT).Method: respectively at mouse stomach glucose solution (1g/kg) back 0min, 30min, 60min, 120min; The eyeground vein clump is got blood; Blood glucose value with each time point of determination of glucose oxidase; And area (AUC) under the calculating blood glucose curve, computational methods: mmol.h/L=(A+B) * 15/60+ (B+C) * 15/60+ (C+D) * 30/60 (A, B, C, D are respectively 0,30,60,120min blood glucose value).
3. experimental result
The result shows that behind the glucose of lumbar injection same dose, all mouse blood sugars progressively descend after all raising earlier, present the metabolic process of glucose absorption.Each group and normal group relatively, each time point blood glucose value and AUC all have significant differences (P < 0.001), show diabetic mice modeling success.When giving glucose load 0min, glyburide group, xanthosine group, Pueraria lobota-Huang are organized and are compared with model group, and its FBG (fasting glucose) has significant difference (P < 0.05); When giving behind the glucose load 30min, glyburide group blood glucose value is starkly lower than model group (P < 0.05), though all the other respectively organize medicine reduction trend, there was no significant difference is arranged; When giving behind the glucose load 60min, Pueraria lobota ketone group, xanthosine group and Pueraria lobota-yellow effective site group blood glucose value obviously lower (P < 0.05); When giving behind the glucose load 120min, each drug group blood glucose value is compared with model group, difference that there are no significant; Calculate and respectively to organize area under the glucose tolerance curve (AUC), find that glyburide group, Pueraria lobota ketone group, Pueraria lobota-yellow effective site group AUC value are starkly lower than model group (P < 0.05).The result shows that glyburide, Radix Puerariae total flavones, Radix Astragali total saponins and Pueraria lobota-yellow effective site all can reduce the FBG of diabetic mice; Improve the carbohydrate tolerance of diabetic mice; And Pueraria lobota-yellow effective site group effect is superior to Radix Puerariae total flavones, Radix Astragali total saponins, explains that both have collaborative blood sugar lowering and the effect that improves carbohydrate tolerance.The result sees table 1.1
Table 1.1 Pueraria lobota-yellow effective site to the influence of diabetic mice carbohydrate tolerance due to the STZ (x ± s, n=12)
Annotate: compare with normal group
*P<0.001; Compare △ P with model group<0.05;
4. brief summary
Radix Puerariae total flavones, Radix Astragali total saponins and Pueraria lobota-yellow effective site all can reduce the FBG of diabetic mice; Improve the carbohydrate tolerance of diabetic mice; And Pueraria lobota-yellow effective site group effect is superior to Radix Puerariae total flavones, Radix Astragali total saponins, explains that both have collaborative blood sugar lowering and the effect that improves carbohydrate tolerance.
Two, the medicine efficacy screening of Pueraria lobota-effective site insulin resistant experiment
1 material:
1.1 animal: the KM mice, male, body weight (20 ± 2) g, cleaning level.
1.2 reagent and instrument:
Receive the reagent thing: drug regimen of the present invention (contains Radix Puerariae total flavones 50g, purity 60%; Radix Astragali total saponins 25g, purity 60%), Radix Puerariae total flavones, purity 60%; Radix Astragali total saponins, purity 60%; Provide by Traditional Chinese Medicine University Of Guangzhou new drug development research center; Rosiglitazone, specification: 4mg/ sheet, Guizhou Shengjitang Pharmaceutical Co., Ltd.; Glucose, citric acid, sodium citrate are analytical pure; Streptozotocin (STZ), U.S. sigma company produces; The blood glucose test kit; Hydrocortisone sodium succinate (HCSS) faces with preceding and is mixed with 7mg/mL solution with normal saline; Regular iletin; Face with preceding with normal saline be mixed with 0.025
; The blood glucose test kit,
appearance.
2 experimental techniques
2.1 experimental principle:
HCSS can come inducing mouse to produce insulin resistant through the substance metabolism that influences body sugar, fat, protein etc.The fasting glucose difference of this insulin resistant model mice fasting glucose and normal mouse is little, and carbohydrate tolerance is but obviously unusual, is similar to that insulin sensitivity obviously reduces and " healthy subjects " that do not form diabetes as yet.For the mice of this insulin resistant model, behind the insulin of lumbar injection doses, observe its change of blood sugar, can embody the interior insulin of mice body to the metabolic ability of blood glucose, thus the insulin sensitivity of reflection mice.
2.2 dosage converts:
Medicine centering, the ratio of the Radix Puerariae and the Radix Astragali are 1: 1 (Radix Puerariae 30g, Radix Astragali 30g).Investigate according to medical material, content of total flavone is 40.0mg/g in the used medical material Radix Puerariae, and total saponin content is 20mg/g in the Radix Astragali.According to 100% rate of transform and extract purity; Clinical equivalent dosage according to people's per kilogram of body weight (60kg) conversion mice is respectively: Pueraria lobota ketone (Radix Puerariae total flavones) is 335mg/kg; Xanthosine (Radix Astragali total saponins) is 165mg/kg, and Pueraria lobota-yellow effective site is 500mg/kg (Radix Puerariae total flavones is 165mg/kg for the 335mg/kg+ Radix Astragali total saponins).
2.3 experimental technique:
Get some of KM mices, male and female half and half are divided into 14 groups at random by table 1.Each organizes gastric infusion while subcutaneous injection HCSS70mg/ (kgd) (7mg/ml), normal control group subcutaneous injection normal saline, 9d continuously.Fasting 3h before the administration on the 10th, gastric infusion is 1 time again, and 1h pneumoretroperitoneum injection (ip) insulin 0.5U/kg measures and gives behind the insulin 0,40, the blood glucose value during 120min, calculates and gives the percentage rate that blood glucose descends behind the insulin.
3. experimental result
The result shows that behind the insulin of ip same dose, mouse blood sugar is on a declining curve, and each treated animal blood glucose all has decline by a relatively large margin behind the 30min, and each treated animal blood glucose value all gos up to some extent during 120min, but it is different with the rise amplitude to descend.Wherein when 30min, 120min, model group is compared with the normal control group, and the blood glucose rate of descent has significant difference (P < 0.05).Compare with model group: rosiglitazone group 30mjn, 120min blood glucose rate of descent have significant difference (P < 0.05); There were significant differences (P < 0.05) for the blood glucose rate of descent during Pueraria lobota ketone group 30min; The blood glucose rate of descent all has significant differences (P < 0.01 when xanthosine group, Pueraria lobota-Huang group 30min, 120min; P 0.001).Prompting Radix Puerariae total flavones, Radix Astragali total saponins, Pueraria lobota-yellow effective site all can improve the insulin sensitivity of insulin resistant mice due to the HCSS; And Pueraria lobota-yellow effective site group effect is superior to Radix Puerariae total flavones, Radix Astragali total saponins, explains that both have the collaborative insulin resistant effect that improves.The result sees table 2.1
Table 2.1 respectively organize medicine to the influence of the inductive insulin resistant mouse blood sugar of HCSS (x ± s, n=9)
Annotate: compare with normal group
*P<0.05
Compare △ P < 0.05 with model group; △ △ P < 0.01; △ △ △ P < 0.001
4. brief summary
Radix Puerariae total flavones, Radix Astragali total saponins, Pueraria lobota-yellow effective site all can improve the insulin sensitivity of insulin resistant mice due to the HCSS; And Pueraria lobota-yellow effective site group effect is superior to Radix Puerariae total flavones, Radix Astragali total saponins, explains that both have the collaborative insulin resistant effect that improves.
Three, Pueraria lobota-yellow effective site is to intervention effect and the Mechanism Study of type 2 diabetes mellitus rat
1 material:
1.1 animal:
The SD rat, male, body weight 200 ± 20g, the SPF level is provided by Guangdong Medical Lab Animal Center.
1.2 reagent and reagent:
Receive the reagent thing: drug regimen of the present invention (contains Radix Puerariae total flavones 50g, purity 60%; Radix Astragali total saponins 25g, purity 60%), Radix Puerariae total flavones, purity 60%; Radix Astragali total saponins, purity 60%; Luogelie ketone hydrochloride, specification: 4mg/ sheet, Guizhou Shengjitang Pharmaceutical Co., Ltd..Glucose, citric acid, sodium citrate are analytical pure; Streptozotocin (STZ), U.S. sigma company produces; The blood glucose test kit; T-CHOL test kit, triglyceride test kit, high density lipoprotein test kit, low density lipoprotein, LDL test kit, insulin are put a complete set of test kit of the agent of being excused from an examination, tumor necrosis factor radioimmunological kit, leptin radioimmunological kit, GLUT-4 and IRS-1 SABC, RT-PCR test kit; The high heat feedstuff is processed by Guangdong Medical Lab Animal Center.
1.3 instrument:
Spectrophotometer; ELIASA; The electric heating constant temperature tank; Luo Shi blood glucose meter, blood sugar test paper
14 statistical method
All data are all added up with the SPSS statistical software, relatively use variance analysis (AVONA) between two groups.
2. experimental design
2.1 animal divides into groups
Select 50 of the successful type 2 diabetes mellitus rats of modeling, be divided into 5 groups at random, be respectively model control group, positive control drug Luogelie ketone hydrochloride group, the Pueraria lobota-high, medium and low dose groups of yellow effective site.Other gets with criticizing normal rat as normal group, 10 of every treated animals.
2.2 dosage design
Medicine centering, the ratio of the Radix Puerariae and the Radix Astragali are 1: 1 (Radix Puerariae 30g, Radix Astragali 30g).Investigate according to medical material, content of total flavone is 40.0mg/g in the used medical material Radix Puerariae, and total saponin content is 20mg/g in the Radix Astragali.According to 100% rate of transform and extract purity; Clinical equivalent dosage according to people's per kilogram of body weight (60kg) conversion rat is respectively: Pueraria lobota ketone (Radix Puerariae total flavones) is 200mg/kg; Xanthosine (Radix Astragali total saponins) is 100mg/kg, and Pueraria lobota-yellow effective site is 300mg/kg (Radix Puerariae total flavones is 100mg/kg for the 200mg/kg+ Radix Astragali total saponins).The high, medium and low dose groups dosage of Pueraria lobota-yellow effective site is respectively 600mg/kg, 300mg/kg, 150mg/kg body weight, and Luogelie ketone hydrochloride dosage is the 1mg/kg body weight.
2.3 medication
Gastric infusion.Wherein normal group and matched group are irritated stomach with water, and the administration volume is the 1ml/100g body weight, and be administered once every day, 8 weeks of successive administration.
2.4 zoopery and drawing materials
After the beginning administration, remove rats in normal control group and feed normal diet, all the other each groups continue to feed with the high heat feedstuff.Claim the body constitution amount weekly, the record weighing results, by new body constitution amount adjustment dose, food-intake and the amount of drinking water of rat respectively organized in monitoring simultaneously, and observes the general state of rat.In carrying out glucose tolerance experiment (OGTT), insulin tolerance experiment (ITT) in the 8th week of administration.When experiment finishes; Rat fasting 12h; Use chloral hydrate anesthesia, abdominal aortic blood is measured fasting glucose (FBG), blood fat four (TC, TG, HDL-C, LDL-C) and free fatties (FFA), measures serum insulin (FINS), TNF-α, leptin (Leptin) simultaneously; Other gets the part liver, measures TC, TG, HDL-C, LDL-C, FFA in the liver.Sharp separation part liver skeletal muscle and intraperitoneal fatty tissue place liquid nitrogen freezing rapidly; Place-80 ℃ of cryogenic refrigerators to preserve then, be used to detect the expression of GLUT-4 (GLUT-4) mRNA, IRS-1 (IRS-1) mRNA, PPAR-YmRNA.Get liver, skeletal muscle and fatty tissue in addition respectively and place neutral formalin fixing, carry out immunohistochemical assay after the section, measure GLUT-4 and the proteic expression of IRS-1 in the tissue.Separate pancreas, be fixed in the neutral formalin, section is done HE dyeing, pathologic finding.
3. experimental technique and index detect
3.12 the modelling of type diabetes rat
Some of male SD rats, body weight 180～220g after adaptability in the breeding observing chamber is raised 7d, gets 10 as the normal control group; Feed with normal feedstuff, all the other rats feed with high heat feedstuff (prescription composition: normal feedstuff 52%, casein 12%, sucrose 10%; Adeps Sus domestica 24%, calcium hydrogen phosphate 2%, compound various vitamins 0.1%; Mineral 0.4%, salt 0.2%, totally 100.7%); In continuous 4 weeks, give lumbar injection STZ solution 30mg/kg behind the fasting 12h, fasting 12h behind the Yu Yizhou; The eye socket venous plexus is got the blood glucose value that blood system is not measured fasting glucose and glucose load (1g/kg) back 2h, selects fasting glucose rat normal and impaired glucose tolerance to confirm as the type 2 diabetes mellitus rat, and continues simultaneously to feed with high lipid food in administration.
3.2 oral glucose tolerance experiment (OGTT)
Behind the animal fasting 12h; Respectively at rat oral gavage glucose solution (1g/kg) back 0min, 30min, 60min, 120min; The tail vein is got blood; Measure the blood glucose value of each time point with blood sugar test paper, and calculate area (AUC) under the blood glucose curve, computational methods: mmol.h/L=(A+B) * 15/60+ (B+C) * 15/60+ (C+D) * 30/60 (A, B, C, D are respectively 0,30,60,120min blood glucose value).
3.3 insulin tolerance experiment (ITT)
Behind the animal fasting 12h; Respectively at rat skin lower injection insulin solutions (0.3U/kg) back 0min, 40min, 90min; The tail vein is got blood; Measure the blood glucose value of each time point with blood sugar test paper, and calculate area (AUC) under the blood glucose curve, computational methods: mmol.h/L=(A+B) * 20/60+ (B+C) * 25/60 (A, B, C are respectively 0,40,90min blood glucose value).
3.4 fasting glucose (FBG), FPI (FINS) are measured and the evaluation of insulin resistant
FBG adopts determination of glucose oxidase, and FINS adopts to put and exempts from method mensuration, and calculating insulin sensitivity index (ISI)=Ln [1/ (Fins * FBG)] and IR index (HOMA-IR)=(FBG * FINS)/22.5.
3.5 lipid metabolism
After experiment finished, water 12h was can't help in the rat fasting, 7% chloral hydrate anesthesia; Through abdominal aortic blood, 3500rpm/min4 ℃ of centrifugal 15min gets serum; Enzyme process is all adopted in TC, TG, HDL-C, LDL-C and FFA level determination in blood, the liver, operates according to the test kit description.
3.6 the mensuration of cytokine
The level of TNF-α and Leptin adopts to put and exempts from method mensuration in the serum.
3.7 GLUT-4 protein expression in liver, skeletal muscle, the fatty tissue
Adopt the SABC method to measure GLUT-4 and the proteic expression of IRS-1 in liver, skeletal muscle, the fatty tissue.Detailed process mainly contains: 1. tissue slice 5 μ m, and routine dewaxes to water, the distillation washing; 2. 3% hydrogen peroxide is hatched 10min to suppress endogenous peroxidase activity for 37 ℃, and PBS washes 4 * 5min; 3. normal sheep serum is hatched 10min to reduce nonspecific reaction for 37 ℃; 5. 1h is hatched in anti-(1: 100) 37 ℃, and PBS washes 4 * 5min; 6. biotin labeled two is anti-, hatches 10min for 37 ℃, and PBS washes 4 * 5min; 7. the streptavidin peroxidase complex is hatched 10min for 37 ℃, and PBS washes 4 * 5min; 8. DAB colour developing liquid colour developing, tap water flushing cessation reaction; 9. haematoxylin redyeing dewaters, and is transparent, mounting.Replace one to resist with PBS as negative control.10. microphotograph and semi-quantitative analysis (adopt the image analysis system software analysis.
3.8 PPAR-YmRNA expression in GLUT-4mRNA and IRS-1mRNA expression and the fatty tissue in liver, skeletal muscle, the fatty tissue
Process is following:
(1) total RNA extracts: carry out total RNA by the test kit description and extract.The RNA electrophoresis is verified, if 28SRNA:18SRNA approximates 2: 1, explains that then RNA extracts success and not degraded of RNA.
(2) reverse transcription and amplification: get total RNA extract, according to the test kit description operation.
(3) the RT-PCR semi-quantitative results detects: get product and use 2% agarose gel electrophoresis, observed result and taking pictures under the 60V electrophoresis 1hr ultraviolet transmissive lamp is carried out the gray scale measurement through the electrophoretic image analyser, and gene expression dose is represented with gray level ratio.
3.9 pancreatic tissue pathologic finding
After the last administration, rat fasting 12h gets pancreatic tissue, formalin fixed, HE dyeing, FFPE, section, om observation.
3.10 general state inspection: overviews such as body weight, food-intake, amount of drinking water, urine amount.
4. experimental result (part)
4.1 the qualified rat screening of model
After the model group rat adopts high lipid food to feed for 4 weeks; The STZ that ip is low dose of; Filter out 50 of modeling success rats, its fasting glucose and compared with normal have trend of rising, but do not have significant difference; And blood glucose value and compared with normal obviously raise (P < 0.01) behind the glucose load 2h, show the model success.(seeing table 3.1)
Table 3.1 high lipid food is fed and to be added low dose of STZ to the influence of rat carbohydrate tolerance (x ± s)
Annotate: compare with normal group
*P<0.005;
*P<0.01;
* *P<0.001
Compare #P < 0.05 with model group; ##P < 0.01; ###P < 0.001 (together following)
4.2 Pueraria lobota-yellow effective site is to the influence of type 2 diabetes mellitus rat body weight and food-intake and amount of drinking water
Before modeling, each organizes the rat body weight equilibrium, no significant difference; Feeding with high lipid food to the during 4 weeks, each is organized rat and compares rising very obviously (P < 0.001) with the normal rats body weight, and high lipid food is fed and respectively organized body weight no significant difference between the rat; In the week after giving ip STZ was the 5th week, and the weight of animals has significant change, and each treated animal body weight of model intervention obviously descends; Compare zero difference with normal group, also do not have significant difference between each group, show that STZ has influence to the body weight of rat.After the beginning administration; The weight of animals begins to raise; Especially the model group weight increase is obvious; And each drug group rat is compared weight increase with model group slow, and especially dose groups more obvious (P < 0.001) in Pueraria lobota-yellow effective site shows that Pueraria lobota-yellow effective site has the effect that alleviates the caused obesity of type 2 diabetes mellitus.(referring to table 3.2)
At the administration initial stage, each food-intake and amount of drinking water of organizing rat is close, along with the prolongation of administration time; Each food-intake of organizing rat different trend occurs with amount of drinking water; Model group shows a rising trend, and all the other each groups increases slowly, to the 8th week; Each drug group food-intake, amount of drinking water obviously are less than model group, show that Pueraria lobota-yellow effective site has the effect that improves type 2 diabetes mellitus polydipsia polyphagia.
Table 3.2 Pueraria lobota-yellow effective site to the influence of type 2 diabetes mellitus rat body weight (x ± s, n=8)
4.3 Pueraria lobota-yellow effective site is to the influence of type 2 diabetes mellitus rat carbohydrate tolerance
The result shows; Model group and compared with normal; Blood glucose obviously raises behind the glucose load, and area also significantly increases (P < 0.01) under the glucose tolerance experiment blood glucose curve, shows the impaired glucose tolerance of type 2 diabetes mellitus rat; And in rosiglitazone group and Pueraria lobota-yellow effective site dose groups can subtract significantly all that blood glucose behind the diabetes rat glucose load rises and AUC (P 0.05, P 0.01).Explain that dosage in Pueraria lobota-yellow effective site can improve the impaired glucose tolerance of obese rat.(seeing table 3.3)
Table 3.3 Pueraria lobota-yellow effective site to the influence of type 2 diabetes mellitus rat carbohydrate tolerance (x ± s, n=7)
4.4 Pueraria lobota-yellow effective site is to the influence of type 2 diabetes mellitus rat insulin tolerance
The result shows; Model group and compared with normal, the degree that insulin injection 40,90min blood glucose descend be less than normal group, and area AUC is apparently higher than normal group (P < 0.01) under the blood glucose curve; Show that the type 2 diabetes mellitus rat reduces the sensitivity of insulin, has the insulin resistant characteristic.After the pharmaceutical intervention; In Pueraria lobota-yellow effective site behind the dose groups rat insulin injection 40, the degree that descends of 90min blood glucose and AUC be significantly higher than model group (P < 0.05; P 0.01), it is unusual to show in Pueraria lobota-yellow effective site that dosage has an insulin tolerance that improves the type 2 diabetes mellitus rat.(seeing table 3.4)
Table 3.4 Pueraria lobota-yellow effective site to the influence of type 2 diabetes mellitus rat insulin tolerance (x ± s, n=7)
4.5 Pueraria lobota-yellow effective site is to the influence of type 2 diabetes mellitus rat fasting blood-glucose, serum insulin, insulin sensitivity index and insulin resistance index
The result shows; Model group and compared with normal; Its FBG, the obvious height of FINS (P < 0.01), insulin sensitivity index significantly descend (P < 0.001), insulin resistance index significantly increases (P < 0.01), show that the sensitivity that the type 2 diabetes mellitus rat has hyperglycemia, hyperinsulinemia, an insulin reduces and the insulin resistant characteristic.Each is organized in the medicine rosiglitazone and has FBG, the FINS of reduction and improve insulin sensitivity, improves the effect (P < 0.01) of insulin resistant, and Pueraria lobota-each dose groups of yellow effective site only high dose has the effect that reduces type 2 diabetes mellitus rat FBG.Therefore Pueraria lobota-yellow effective site is not significantly improved reducing serum insulin, the sensitivity of improving insulin and repellence.(seeing table 3.5)
Table 3.5 Pueraria lobota-yellow effective site to the influence of T2DM rat FBG, FINS, ISI and HOMA-IR (x ± s, n=7)
4.6 Pueraria lobota-yellow effective site is to the influence of type 2 diabetes mellitus lipid metabolism in rats
The result shows, the serum total cholesterol that Pueraria lobota-each dosage of yellow effective site all can significantly reduce rat and low-density lipoprotein white level (P 0.001), and the serum triglycerides that raises is not obviously influenced, each organizes medicine does not all have obvious influence to high density lipoprotein.Show that Pueraria lobota-yellow effective site has the effect of certain blood fat reducing.(seeing table 3.6)
Table 3.6 Pueraria lobota-yellow effective site to the influence of type 2 diabetes mellitus lipid metabolism in rats (x ± s, n=7)
4.7 Pueraria lobota-yellow effective site is to the influence of type 2 diabetes mellitus rat TNF-α and Leptin content
The result shows; In Pueraria lobota-yellow effective site, low dosage all can significantly reduce TNF-α and Leptin level in the serum of rat (P < 0.01); Wherein but the reduction Leptin level of Pueraria lobota-yellow effective site low dosage highly significant shows that Pueraria lobota-yellow effective site has significant inhibitory effect to TNF-α and Leptin.(seeing table 3.7)
Table 3.7 Pueraria lobota-yellow effective site to the influence of type 2 diabetes mellitus rat TNF-α and Leptin level (x ± s, n=7)
4.8 Pueraria lobota-yellow effective site is to the influence of type 2 diabetes mellitus pancreas in rat tectology
The pancreatic tissue morphological observation
1. the normal rats pancreatic cell is evenly distributed, the islets of langerhans structural integrity, and edge clear, endocrine body of gland islets of langerhans and external secretion body of gland no abnormality seen change.
2. model group insulin resistance rat pancreatic cell distribution uniform, but islets of langerhans edge blurry, structural intergrity receives certain destruction, and the islets of langerhans fibroblast increases and acinus interstitial fibers hamartoplasia.
3. rosiglitazone group pancreatic tissue mild or moderate is congested, and pancreatic cell is evenly distributed, islets of langerhans structural integrity, edge clear, the slight hypertrophy of fibrous tissue between acinus.
4. Pueraria lobota-yellow effective site high dose group pancreas in rat cell distribution is even, the islets of langerhans structural integrity, and fibroblast slightly increases in the edge clear, islets of langerhans.
5. dose groups pancreas in rat cell distribution is even in Pueraria lobota-yellow effective site, islets of langerhans structural integrity, edge clear, acinus interstitial fibers hamartoplasia.
6. Pueraria lobota-yellow effective site low dose group pancreatic tissue, pancreatic cell is evenly distributed, the islets of langerhans edge blurry, structural intergrity is damaged, and the islets of langerhans fibroblast is slight to be increased and acinus interstitial fibers hamartoplasia.
4.7 the influence that Pueraria lobota-yellow effective site is expressed GLUT-4 in type 2 diabetes mellitus rat liver, skeletal muscle and the fatty tissue
The result shows; Luogelie ketone hydrochloride can significantly increase the proteic expression of GLUT-4 in liver, fat and the skeletal muscle (P < 0.05); The expression that Pueraria lobota-yellow effective site is high, middle dosage all can increase GLUT-4 in the liver (P 0.05), the expression of GLUT-4 in the dosage increase fatty tissue in Pueraria lobota-yellow effective site in addition (P 0.05).
5. brief summary: Pueraria lobota-yellow effective site has certain therapeutical effect to the type 2 diabetes mellitus rat.
Four, the drug regimen of control type 2 diabetes mellitus is to the influence of diabetes rat cardiomyopathy
The I materials and methods
1.1 material
Receive the reagent thing: drug regimen of the present invention (contains Radix Puerariae total flavones 50g, purity 60%; Radix Astragali total saponins 25g, purity 60%), Radix Puerariae total flavones, purity 60%; Radix Astragali total saponins, purity 60%; Luogelie ketone hydrochloride, specification: 4mg/ sheet, Guizhou Shengjitang Pharmaceutical Co., Ltd..Glucose, citric acid, sodium citrate are analytical pure; Streptozotocin (STZ), U.S. sigma company produces; Test kits such as SOD, MDA, Coomassie brilliant blue protein determination all build up bio-engineering research institute available from Nanjing.
1.2 preparation of experimental diabetic rats model and grouping.
Dosage converts: medicine centering, the ratio of the Radix Puerariae and the Radix Astragali are 1: 1 (Radix Puerariae 30g, Radix Astragali 30g).Investigate according to medical material, content of total flavone is 40.0mg/g in the used medical material Radix Puerariae, and total saponin content is 20m in the Radix Astragali.According to 100% rate of transform and extract purity; Clinical equivalent dosage according to people's per kilogram of body weight () conversion rat is respectively: Pueraria lobota ketone (Radix Puerariae total flavones) does; Xanthosine (Radix Astragali total saponins) is 100mg/kg, and Pueraria lobota-yellow effective site is 300mg/kg (Radix Puerariae total flavones is 100mg/kg for the 200mg/kg+ Radix Astragali total saponins).The high, medium and low dose groups dosage of Pueraria lobota-yellow effective site is respectively 600mg/kg, 300mg/kg, 150mg/kg body weight, and Luogelie ketone hydrochloride dosage is the 1mg/kg body weight.
70 of SD rats, male and female half and half, body weight 180g～200g is provided by Guangdong Medical Lab Animal Center.Wherein 60 are used to cause diabetes model, and 10 are used for the normal control group in addition.
List of references adopts streptozotocin (STZ) to increase the fat high caloric diet, causes diabetes rat property cardiomyopathy model.Experiment is divided into normal group, model group, and the positive drug group, Pueraria lobota-yellow effective site is high, in, low dose group.After the normal control group fed for 4 weeks with normal feedstuff, 3ml0.1mmol/L citrate buffer solution lumbar injection, normal feedstuff fed for 8 weeks again; With high lipid food (form: normal feedstuff 52%, casein 12%, sucrose 10% earlier by prescription for diabetic groups; Adeps Sus domestica 24%, calcium hydrogen phosphate 2%, compound various vitamins 0.1%; Mineral 0.4%, salt 0.2%, totally 100.7%) fed for 4 weeks; Adopt 30mg/kg STZ lumbar injection again, 1 week back survey blood glucose is judged as diabetes with impaired glucose tolerance person and becomes the mould rat.To become the mould rat to be divided into five groups (Pueraria lobota-yellow effective site is high for model group, positive drug group, in, low dose group) at random, and administration respectively, every day 1 time, and continue high lipid food and fed for 8 weeks.
1.3 detection index:
1. general state inspection: rat is carried out the observation of general states such as body weight, food-intake, amount of drinking water, urine amount.
2. the collection of blood sample: after experiment finished, water 12h was can't help in the rat fasting, 7% chloral hydrate anesthesia, and through abdominal aortic blood, the centrifugal 15min of 3500rpm/min gets serum, surveys blood pressure and blood lipoid etc.
3. cardiac index detects: after the last administration, rat fasting 12h, put to death each treated animal after; General utility balance takes by weighing rat body weight (BW), takes out heart rapidly, and electronic balance takes by weighing rat heart weight in wet base (HW); Calculate BW/HW ratio, observe the intervention effect of model group cardiac index situation and medicine.
4. cardiac muscular tissue's morphological observation: after the last administration, rat fasting 12h, the dirty tissue of coring places normal saline to wash repeatedly, cleans residual hematocele, inserts 10% neutral formalin solution and fixes; Gradient alcohol dehydration, waxdip, embedding, section, the thick 4um of sheet, HE dyeing, light microscopic is observed the heart tissue morphological change down.Further under Electronic Speculum, observe the influence of rat heart muscle being organized ultramicroscopic morphology: left ventricle is cut into the 1mm3 fritter, and glutaraldehyde is fixed, the phosphate buffer flushing; It is fixing to starve acid, the phosphate buffer flushing, and propylene oxide is transparent; 1 μ m semithin section is cut in the embedding of Epon812 working solution, and acetic acid uranium just dyes; Lead citrate is redyed, and places at last and observes ultrathin section under the transmission electron microscope.
5. oxidation resistance inspection: put to death each treated animal, take out heart rapidly, wipe out peplos, blood vessel; Clean with cold isotonic saline solution, filter paper blots, immediately under 1～4 ℃ of condition; Process the normal saline homogenate of 100g/L cardiac muscular tissue respectively, the centrifugal 15min of 3000rpm/min, it is subsequent use to get supernatant.Detect superoxide dismutase (SOD) in the cardiac muscular tissue, malonaldehyde (MDA) level and protein content are pressed the test kit explanation and are measured, and draw each index absorbance through colorimetry, bring formula into and obtain final data.
All use mean ± standard deviation to represent 1.4 statistical procedures is respectively organized experimental data, the significance of group difference carries out statistical procedures with the t method of inspection.
2 experimental results
2.1 respectively organize the comparison of rat blood sugar
Adopt glucose oxidase method to detect rat blood sugar.Visible by table 4.1, compare diabetic model group rat blood sugar value significantly raise (P < 0.05) with the normal control group; Compare with model group, dose groups, positive drug blood glucose value significantly reduce in Pueraria lobota-yellow effective site, and difference has significance (P < 0.05).
Table 4.1 is respectively organized the variation (x ± SD) of rat blood sugar
Compare with " normal group ", #P < 0.05; ##P < 0.01
Compare with " model group ",
*P<0.05;
*P<(0.01 down together)
2.2 respectively organize the comparison of rat urine amount
Adopt metabolic cage to collect rat 24h urine amount.Visible by table 4.2, to compare with the normal control group, diabetic model group rat urine amount significantly raises, and difference has highly significant property (P < 0.01); Compare with model group, Pueraria lobota-yellow effective site is high, middle dose groups, and positive group urine amount significantly reduces, and difference has significance.
Table 4.2 is respectively organized the variation (x ± SD) of rat urine amount
2.3 respectively organize the variation of rat body weight and cardiac index
The experiment initial stage, the rat random packet, each organizes body weight does not have the statistics difference.Experiment latter stage, the normal group body weight is starkly lower than model group, and significant difference (P < 0.05) is arranged.Pueraria lobota-yellow effective site is high, middle dose groups body weight and model group relatively have utmost point significant difference (P < 0.01), and positive drug group body weight and model group more also have significant difference (P < 0.05).Suppressing aspect the cardiac hypertrophy, the cardiac index of all modeling rats and compared with normal all have in various degree and improve, and through after the medication, Pueraria lobota-yellow effective site is high, middle dose groups, and the positive cardiac index of organizing compares with model group that all there were significant differences.The result sees table 4.3 for details.
Table 4.3 is respectively organized the variation (x ± SD) of rat body weight and cardiac index
2.4 respectively organize the Ultrastructural comparison of rat heart muscle
Normal group: the myocardial cell marshalling, iuntercellular is connected by intercalated disc, and intercalated disc is clear, continuous, structural integrity.Endochylema is full of the sarcostyle that a large amount of parallel longitudinals are arranged, and I band, A band, H band all obviously are prone to distinguish with Z line, M line, form light and dark muscle segment structure.Nucleus is positioned at the myocardial cell central part, and nuclear is interior to be main with euchromatin, and a small amount of heterochromatin is distributed under the nuclear membrane or disperses and is present in the caryoplasm.Abundant mitochondria is arranged in the endochylema, rounded or oval, structural integrity, ridge is intensive, arranges in order, is full of whole mitochondrion.Visible blood capillary between myocardial cell, basement membrane is complete clear.
Model group: the sarcostyle arrangement disorder of myocardial cell, fracture, separation, local dissolution, the fuzzy fracture of intercalated disc distortion, sarcoplasmic reticulum expansion.Nuclear membrane is imperfect and be segmental dissolving disappearance pathological changes, and heterochromatin is condensed.Mitochondrion increases very obvious, is heaped-up, swelling of mitochondria, and ridge fracture, dissolving, mitochondrial matrix dissolving, disappearance form the cavity district.Visible glycogen granule of myocardial cell and fat drip calmness, also can see marrow appearance corpusculum.
Pueraria lobota-yellow effective site:
Secondly high dose group is that middle dose groups is also relatively more normal near normal group, and low dose group then has significantly pathological changes.Wherein, high dose group sarcostyle marshalling, identical with normal group, mitochondrion and karyomorphism are normal, and glycogen granule exists situation similar with normal group.In the dose groups sarcostyle arrange still can, the mitochondrion form is roughly normal, and deformity and swelling pathological changes are arranged individually.The low dose group sarcostyle is arranged with disorderly phenomenon, and myofilament dissolving, fracture pathological changes appear in the part, and mitochondrion makes moderate progress than model group, but still visible degeneration line swelling quite a lot, but whole pathological changes is light than model group.
Positive group: sarcostyle is arranged more neat, and mitochondrion and karyomorphism are normal, and deformity and swelling pathological changes are arranged individually.Glycogen granule exists situation similar with normal group.
2.5 respectively organize the variation of SOD activity, MDA content in the rat heart muscle tissue
Superoxide dismutase in the laboratory animal cardiac muscular tissue (SOD) determination of activity; The SOD activity is lower than normal control group (P < 0.01) in the diabetic model group rat heart; Behind Pueraria lobota-yellow effective site therapeutic intervention, SOD is active in the heart raises, remarkable with the diabetic groups comparing difference.And content model group and the compared with normal of oxidation product MDA significantly raise (P < 0.05), and Pueraria lobota-yellow effective site intervention group reduces (P < 0.05) than model group.Above presentation of results Pueraria lobota-yellow effective site can improve the oxidation resistance of cardiac muscular tissue.
3. brief summary
Experimental result shows that Pueraria lobota-yellow effective site has protective effect to the cardiomyopathy of diabetes rat.
Claims (6)
1. a pharmaceutical composition of preventing and treating type 2 diabetes mellitus is characterized in that being made up of following materials of weight proportions medicine: 40～50 parts of Radix Puerariae total flavoness, 20～25 parts of Radix Astragali total saponinss;
Said Radix Puerariae total flavones by Radix Puerariae crude drug decoction pieces, adds 12 times of amount 80% alcohol heating reflux 2 times, and each 2 hours, filter medicinal residues, merging filtrate, gained filtrating is carried out decompression recycling ethanol and is made medicinal liquid; AB-8 macroporous resin adsorption on the above-mentioned medicinal liquid, last appearance concentration is 0.1g crude drug/ml, applied sample amount is 10BV, flow velocity 1ml/min, preadsorption 2 hours heavily adsorbs 2 times, adsorption site is washed to there not being reducing sugar reaction again; Adsorption site carries out 50% ethanol 10BV volume and carries out eluting, and flow velocity is 2ml/min, and decompression recycling ethanol liquid is ground into 14 order granules with pulverizer after the lyophilization, and total flavones purity 60% makes Radix Puerariae total flavones;
Said Radix Astragali total saponins adds 10 times of amount 60% alcohol heating reflux 2 times by Radix Astragali decoction pieces, and each 2 hours, filter medicinal residues, merging filtrate, gained filtrating is carried out decompression recycling ethanol and is made medicinal liquid; AB-8 macroporous resin adsorption on the above-mentioned medicinal liquid, last appearance concentration is 0.1g crude drug/ml, applied sample amount is 10BV, flow velocity 1ml/min, preadsorption 2 hours heavily adsorbs 2 times, adsorption site is washed to there not being reducing sugar reaction again; Adsorption site is with 0.5% sodium hydroxide eluting, and flow velocity is 2ml/min, and continuing is washed till neutrality with 10% ethanol; Reuse 80% ethanol 10BV volume eluting; Flow velocity is 2ml/min, and decompression recycling ethanol liquid is ground into 14 order granules with pulverizer after the lyophilization; Total saponins purity 60% makes Radix Astragali total saponins.
2. the pharmaceutical composition of control type 2 diabetes mellitus according to claim 1 is characterized in that each composition weight proportion is preferably: 50 parts of Radix Puerariae total flavoness, 25 parts of Radix Astragali total saponinss.
3. the pharmaceutical composition of control type 2 diabetes mellitus according to claim 1 is characterized in that: said pharmaceutical composition thing is applied in the endocrine system disease aspect, is used for the prevention and the treatment of type 2 diabetes mellitus.
4. the pharmaceutical composition of control type 2 diabetes mellitus according to claim 1 is characterized in that: said this pharmaceutical composition thing and extract or refining thing can add conventional adjuvant or excipient, process clinical acceptable forms, are peroral dosage form.
5. the pharmaceutical composition of control type 2 diabetes mellitus according to claim 4 is characterized in that: said peroral dosage form is selected from a kind of in the middle of the pill, tablet, capsule.
6. a preparation of drug combination method of preventing and treating type 2 diabetes mellitus is characterized in that, comprises the steps:
1., preparation Radix Puerariae total flavones
Get the Radix Puerariae decoction pieces and add 12 times of amount 80% alcohol heating reflux 2 times, each 2 hours, filter medicinal residues, merging filtrate, gained filtrating is carried out decompression recycling ethanol and is made medicinal liquid; AB-8 macroporous resin adsorption on the above-mentioned medicinal liquid, last appearance concentration is 0.1g crude drug/ml, applied sample amount is 10BV, flow velocity 1ml/min, preadsorption 2 hours heavily adsorbs 2 times, adsorption site is washed to there not being reducing sugar reaction again; Adsorption site carries out 50% ethanol 10BV volume and carries out eluting, and flow velocity is 2ml/min, and decompression recycling ethanol liquid is ground into 14 order granules with pulverizer after the lyophilization, and total flavones purity 60% is subsequent use;
2., preparation Radix Astragali total saponins
Get Radix Astragali decoction pieces and add 10 times of amount 60% alcohol heating reflux 2 times, each 2 hours, filter medicinal residues, merging filtrate, gained filtrating is carried out decompression recycling ethanol and is made medicinal liquid; AB-8 macroporous resin adsorption on the above-mentioned medicinal liquid, last appearance concentration is 0.1g crude drug/ml, applied sample amount is 10BV, flow velocity 1ml/min, preadsorption 2 hours heavily adsorbs 2 times, adsorption site is washed to there not being reducing sugar reaction again; Adsorption site is with 0.5% sodium hydroxide eluting, and flow velocity is 2ml/min, and continuing is washed till neutrality with 10% ethanol; Reuse 80% ethanol 10BV volume eluting, flow velocity is 2ml/min, decompression recycling ethanol liquid; Be ground into 14 order granules with pulverizer after the lyophilization, total saponins purity 60%, subsequent use;
3., the Radix Puerariae total flavones with above-mentioned preparation, Radix Astragali total saponins, press each composition weight proportion of pharmaceutical composition: 40～50 parts of Radix Puerariae total flavoness, 20～25 parts of Radix Astragali total saponinss, above material mixing stirs, and makes pharmaceutical composition then.
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| CN1682862A (en) * | 2005-02-24 | 2005-10-19 | 四川科伦药业股份有限公司 | Method for preparing astragalus root saponin |
| CN1725956A (en) * | 2002-10-15 | 2006-01-25 | 嘉吉公司 | Improved process for producing cocoa butter and cocoa powder by liquefied gas extraction |
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| CN1562057A (en) * | 2004-03-31 | 2005-01-12 | 成都和康药业有限责任公司 | Medicinal composition for treating cardiocerobral diseases |
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| 段秀梅等.皂苷治疗糖尿病及并发症的研究进展.《中药材》.2007,第30卷(第6期),748－752. * |
| 鲍余生等.黄芪注射液并葛根素注射液治疗2型糖尿病临床观察.《中医药临床杂志》.2007,第19卷(第4期),369-370. * |
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