CN112675186B - Pharmaceutical composition and application thereof - Google Patents

Abstract

The invention relates to a pharmaceutical composition and application thereof, and the pharmaceutical composition mainly comprises harpagide, harpagoside, verbascoside, cinnamic acid, ferulic acid and p-coumaric acid. The pharmaceutical composition can reduce the levels of fasting blood sugar and glycated serum protein and improve the blood sugar regulation capability; regulating blood lipid disorder and improving blood lipid metabolism; relieving insulin hyposecretion; improving insulin resistance level, increasing insulin sensitivity of body, and protecting islet cells. Therefore, the pharmaceutical composition has a better effect of improving type 2 diabetes, and can be used for preparing a medicament for treating type 2 diabetes.

Description

Pharmaceutical composition and application thereof

Technical Field

The invention relates to a pharmaceutical composition, in particular to a pharmaceutical composition and application thereof in preparing a medicament for treating type 2 diabetes.

Background

Type 2 diabetes (T2DM) is the most common type of diabetes, accounting for over 90% of all diabetic patients, and is a metabolic syndrome with a very complex pathophysiological basis, the main pathology of which is represented by a relative insufficiency of insulin secretion or a decrease in the sensitivity of the body to insulin.

At present, the medicines clinically used for treating T2DM mainly comprise chemical medicines such as biguanides, meglitinides, thiazolidinones, sulfonylureas, alpha-glucosidase inhibitors, glucagon-like peptide-1 analogues, DPP-4 inhibitors, insulin and the like, and are often accompanied by side effects of different types and degrees; and with the increase of diabetes patients year by year, the medical expenditure for treating diabetes is increased year by year, so that the development of a new type-2 diabetes treatment medicine which is safer and has low toxic and side effects has important practical significance.

The traditional compound medicine is increasingly paid attention to by virtue of the action characteristics of multiple components, multiple targets and overall view for a long time, but becomes a bottleneck restricting the traditional compound medicine from going to the world due to the complex components and unclear material basis.

The invention relates to a pharmaceutical composition for treating type 2 diabetes, which is prepared from a classical famous prescription decoction for increasing fluid. Zengye Tang, from volume two in Wen Bing tiao Bian, compiled by Wu Jutong Qing dynasty, is prepared from three commonly used yin-nourishing herbs, named Xuan Shen, Sheng Di and Mai Dong, in the ratio of 5: 4: the composition 4 has the functions of nourishing yin, increasing fluid and moistening intestines, is mainly used for treating yang-brightness body fluid burn and constipation due to intestinal dryness with little pathogen and much deficiency, and is clinically used as a common prescription for treating yin deficiency and heat excess type diabetes (early stage of type 2 diabetes) in recent years. The literature reports that the decoction for increasing body fluid (Dezhihui, inner Mongolia traditional Chinese medicine, 2007, (01): 34-35; Wangqing, traditional Chinese medicine clinical research, 2016,8(31): 97-9; Zhongrefined, etc., Zhejiang traditional Chinese medicine university report, 2019, 43(08):810 one-dose 813; Hanxie, etc., traditional Chinese medicine modern distance education, 2014,12(10): 15-16; Cheng Han crowd, etc., Hunan traditional Chinese medicine journal, 2012,28(06):32-33) has the effect of improving type 2 diabetes.

Chinese patent CN 111632058A, CN 111358800A, CN 111214476A, CN 110403948A, CN 109125334A, CN 107375308A, CN 105412131A, CN 108451961A, etc. respectively report that verbascoside has the effects of resisting neurodegenerative diseases, preventing senile dementia, resisting inflammation, promoting nerve function recovery, preventing disability and death after neonatal hypoxia ischemic encephalopathy, improving glomerular podocyte injury type kidney diseases, improving pneumonia and improving type 2 diabetic nephropathy.

Chinese patent CN 110123800A, CN 102600120A reports that cinnamic acid has obvious effect of resisting nasopharyngeal carcinoma and poultry virus disease activity. Chinese patent CN 109260188A reports that coumaric acid has the effect of improving human acute lymphocytic leukemia. Chinese patent CN 111481533A, CN 108714146A, CN 104337801A, CN 106256350A, CN 103642850A, CN 111012771A, CN 104083349A, CN 102342926A, CN 102125542A, CN 1718566A and the like respectively report that ferulic acid has the effects of treating vascular diseases, preventing and treating radioactive intestine and brain injury, treating cerebral tissue ischemia injury, having good antioxidant capacity, inhibiting lung inflammatory injury, resisting anxiety, promoting skin wound healing, preventing and treating osteoporosis and preventing and treating senile dementia.

At present, no reports about the effect of the liquid increasing decoction component and the composition thereof on the type 2 diabetes exist, and the composition consisting of the effective components has no report about the treatment of the type 2 diabetes.

Disclosure of Invention

Aiming at the defects of the existing clinical treatment of type 2 diabetes, the invention aims to provide a pharmaceutical composition with the effects of reducing blood sugar and blood fat and application thereof in preparing a medicament for treating type 2 diabetes.

Technical scheme

A pharmaceutical composition characterized by: comprises harpagide, harpagoside, acteoside, cinnamic acid, ferulic acid, and p-coumaric acid.

Further, the method comprises the following steps:

a pharmaceutical composition is characterized in that the pharmaceutical composition comprises 1500 mu g/mL of harpagoside 700-.

The application of the pharmaceutical composition in preparing the medicament for treating type 2 diabetes is provided.

Specifically, the method comprises the following steps: the invention is obtained by the following steps:

a pharmaceutical composition for treating type 2 diabetes is characterized by comprising the following components (by weight ratio), harpagide (708.632-1417.264 μ g/ml), harpagoside (207.128-414.256 μ g/ml), verbascoside (139.352-278.704 μ g/ml), cinnamic acid (116.632-233.264 μ g/ml), ferulic acid (11.92-23.84 μ g/ml), and p-coumaric acid (12.192-23.384 μ g/ml);

prepared by the following method and steps:

a. the decoction for increasing body fluid is prepared from radix scrophulariae, radix rehmanniae, and radix Ophiopogonis 5: 4: 4, carrying out hydrothermal extraction for 3 times in an amount which is 10 times, 8 times and 6 times, each time for 1h, combining the extracting solutions, carrying out rotary evaporation in a water bath at 55 ℃, and freeze-drying the obtained extract into freeze-dried powder, wherein the yield is 75.38%.

And b, measuring the content of harpagide, harpagoside, verbascoside, cinnamic acid, ferulic acid and p-coumaric acid in the liquid increasing soup by HPLC.

c. The medicine composition solution with equal dosage is prepared according to the proportion of 6 monomer components in the liquid increasing soup.

d. Preparing the solution with the concentration 2 times that of the solution in the step c according to the proportion of the 6 monomer components in the liquid increasing soup, namely the high-dose medicinal composition solution.

The pharmaceutical composition prepared by the method is characterized in that the main chemical components are harpagide, harpagoside, verbascoside, cinnamic acid, ferulic acid and p-coumaric acid, and the weight ratio of the harpagide, the harpagoside, the verbascoside, the cinnamic acid, the ferulic acid and the p-coumaric acid is 708.632-1417.264 mu g/ml, 207.128-414.256 mu g/ml, 139.352-278.704 mu g/ml, 116.632-233.264 mu g/ml, 11.92-23.84 mu g/ml and 12.192-23.384 mu g/ml respectively.

Pharmacodynamic experiment results show that the pharmaceutical composition prepared by the invention can reduce blood sugar and blood fat of type 2 diabetes model rats, has simple extraction process and low cost, and can be used for preparing medicines for treating type 2 diabetes.

Has the advantages that:

as the common general knowledge in the field of traditional Chinese medicine, the traditional Chinese medicine compound decoction has the best effect generally, but the preparation is complex, the storage is difficult, the administration is large, and the traditional Chinese medicine compound decoction is difficult to accept by patients. Therefore, the traditional Chinese medicine formula needs to be optimized or simplified, wherein the important idea is to use the main components to carry out the formula, but unfortunately, the effect is greatly reduced after the main components are used for the formula, for a plurality of reasons, such as the complex components generated by the original formula are synergistic or new components are generated to participate in the drug effect, and the like, so that the problem that the traditional active ingredient formula with the drug effect can be kept in the field of traditional Chinese medicine is always needed to be solved in the field, and if the effect of the active ingredient formula is better than that of the original formula, the difficulty is higher and the solution is more difficult to solve.

The invention simplifies the liquid increasing soup, particularly replaces the traditional Chinese medicinal materials with main components to prepare the liquid increasing soup again, surprisingly, the result after the formula is superior to the original liquid increasing soup, the blood sugar and the blood fat of a type 2 diabetes model rat can be obviously reduced, meanwhile, the preparation is simpler, the dosage of a patient is smaller, and the preparation of tablets and the like is more convenient. As for the registration of the medicine, the process is simpler, the quality is more controllable, and the method belongs to a part of the modernization of the traditional Chinese medicine.

Drawings

Fig. 1(a) is the body weight of the rat 3 weeks after the high fat diet was fed, and fig. 1(B) is the fasting blood glucose value 3 days after the injection of streptozotocin. P <0.01, p <0.001, compared to control.

FIG. 2(A) shows the body weight of rats 3 weeks after administration, and FIG. 2(B) shows the food intake of rats 3 weeks after administration. #, p <0.01, # #, p <0.001, compared to the blank group; p <0.05, p <0.01, p <0.001, compared to the model group. Group C is a control group; m is a model group; DM group is an equivalent pharmaceutical composition. DH, high amount pharmaceutical composition. ZYD, 8g/kg liquid increasing soup. MET, 25mg/kg metformin.

Fig. 3(a) is fasting blood glucose 24 days after administration to rats, fig. 3(B) is GSP concentration 24 days after administration to rats, fig. 3(C) is Oral Glucose Tolerance Test (OGTT) three weeks after administration to rats, and fig. 3(D) is area under the OGTT blood glucose curve. #, p <0.01, # #, p <0.001, compared to the blank group; p <0.05, p <0.01, p <0.001, compared to the model group.

FIG. 4(A) is the triglyceride concentration 24 days after administration to rats, FIG. 4(B) is the total cholesterol concentration 24 days after administration to rats, and FIG. 4(C) is the low density lipoprotein concentration 24 days after administration to rats. #, p <0.01, # #, p <0.001, compared to the blank group; ns, p >0.05, p <0.01, p <0.001, compared to the model set.

FIG. 5(A) is the concentration of fasting insulin 24 days after rat administration, FIG. 5(B) is the insulin resistance index (HOMA-IR), and FIG. 5(C) is the insulin sensitivity index (HOMA-ISI). #, p <0.01, # #, p <0.001, compared to the blank group; ns, p >0.05, p <0.01, p <0.001, compared to the model set.

Fig. 6 is an HE stain (x 200) of control, model, equivalent pharmaceutical composition, high amount pharmaceutical composition, fluid increasing soup, metformin 6 respective pancreatic tissues.

Detailed Description

EXAMPLE 1 preparation of 6 pharmaceutical compositions of verbascoside, harpagide, harpagoside, cinnamic acid, p-coumaric acid, ferulic acid

1. Materials: comparison products: acteoside (Acteoside), harpagide (harpagoside), harpagoside (harpagoside) are purchased from Vickers Biotech limited, Sichuan province (purity is more than or equal to 98%), cinamic acid (cinnamic acid), p-coumaric acid (p-coumaric acid) and ferulic acid (ferulic acid) are purchased from Dougui scientific development Limited, and the purity of the reference products reaches more than 98%. Figwort root, rehmannia root, dwarf lilyturf tuber (Nanjing department of traditional Chinese medicine outpatient service), methanol (Shanghai star can be high-purity solvent Co., Ltd.), acetonitrile (Merck, Germany), formic acid (Aladdin Biotechnology Co., Ltd.), pure water (Drech Drinking Water Co., Ltd.), and n-butanol (Sinopharm Chemical Reagent Co. Ltd.).

2. The instrument comprises the following steps: Milli-Q ultrapure water meter (Millipore corporation, usa), low temperature centrifuge (Beckman corporation, germany), freeze dryer (beijing tetracyclic scientific instrument factory, ltd), electronic analytical balance (mettler-toledo international trade (shanghai) ltd), constant temperature water bath (gorgeon instruments manufacturing ltd, jiangsu jintan city), HQ-300E type ultrasonic cleaner (ultrasonic instruments ltd, kunshan), shimadzu LC-2010C liquid chromatography system (shimadzu, ltd).

3. Preparation of soup for increasing body fluid

The decoction for increasing body fluid is prepared from radix scrophulariae, radix rehmanniae, and radix Ophiopogonis 5: 4: 4, carrying out hydrothermal extraction for 3 times in an amount which is 10 times, 8 times and 6 times, each time for 1h, combining the extracting solutions, carrying out rotary evaporation in a water bath at 55 ℃, and freeze-drying the obtained extract into freeze-dried powder, wherein the yield is 75.38%.

4. HPLC (high performance liquid chromatography) is used for measuring the content of harpagide, harpagoside, verbascoside, cinnamic acid, p-coumaric acid and ferulic acid in the liquid increasing soup

The content of 6 compounds is finally determined by establishing a standard curve of 6 compounds of harpagide, harpagoside, verbascoside, cinnamic acid, p-coumaric acid and ferulic acid, and the measurement results are shown in table 1.

Table 1 measurement of contents of each component in the decoction for increasing blood volume (μ g/g, n ═ 3)

5. Preparation of harpagide, harpagoside, acteoside, cinnamic acid, ferulic acid and p-coumaric acid pharmaceutical composition

According to the proportion of the 6 components in the fluid increasing soup, each 1mL of the fluid increasing soup respectively contains 708.632 mug, 207.128 mug, 139.352 mug, 116.632 mug, 11.92 mug and 12.192 mug of harpagide, harpagoside, verbascoside, cinnamic acid, ferulic acid and p-coumaric acid, namely the equal-dosage pharmaceutical composition solution (DM).

According to the proportion of the 6 components in the fluid increasing soup, each 1mL of the fluid increasing soup is prepared to contain 1417.264 mug, 414.256 mug, 278.704 mug, 233.264 mug, 23.84 mug and 24.384 mug of harpagoside, verbascoside, cinnamic acid, ferulic acid and p-coumaric acid respectively, namely the high-dose pharmaceutical composition solution (DH).

Example 2 Effect of harpagide, harpagoside, verbascoside, cinnamic acid, ferulic acid, p-coumaric acid compositions on type 2 diabetic rats

1. Materials: high-fat feed (Jiangsu province cooperative medical bioengineering, llc), streptozotocin (STZ, BIOFoxx, Germany), rat INS assay kit (Shanghai science, biology, Inc.) Glucose (alpha-D-Glucose, Aladdin, Inc.), metformin hydrochloride tablet (Shanghai Shi Guibao pharmacy, Inc., China and America), glycogen content, Glycated Serum Protein (GSP), total cholesterol (T-CHO), Triglyceride (TG), low-density lipoprotein (LDL-C) assay kits were purchased from Nanjing institute of bioengineering. The drug to be tested was the solution of the pharmaceutical composition prepared in example 1.

2. The instrument comprises the following steps: microplate reader (Bio-Tek, USA), low temperature centrifuge (Thermo), blood glucose meter (Roche diagnostics GmbH, Germany), PHS-3BW pH meter (Banner instruments GmbH, Shanghai).

3. Pharmaceutical formulation

High-fat feed: 10% of lard, 10% of egg yolk, 1% of cholesterol, 0.2% of cholate and 78.8% of common feed. Metformin hydrochloride solution: taking a proper amount of metformin tablets, crushing, preparing a solution with the concentration of 25mg/mL by using double distilled water, and storing at 4 ℃. Liquid increasing soup: dissolving the fluid increasing decoction freeze-dried powder in double distilled water to prepare fluid increasing decoction solution with the concentration of 0.8 g/mL. Glucose solution: taking a proper amount of glucose powder, dissolving the glucose powder in double distilled water to prepare a glucose solution with the concentration of 0.2 g/mL.

Citric acid-sodium citrate buffer: dissolving 1.05g of citric acid (FW 210.14) in 50mL of double distilled water to obtain solution A; 1.47g of sodium citrate (FW,294.10) was dissolved in 50mL of double distilled water to obtain solution B. The solutions A and B were mixed (v/v,1:1.32), the pH was measured, and the pH was adjusted to 4.25. Filtering with 0.22 μm filter membrane, and refrigerating at 4 deg.C.

Streptozotocin (STZ) solution: 50mg of STZ powder is weighed to be three parts, and the three parts are placed in a centrifugal tube wrapped by tinfoil paper and placed in an ice bath together with a citric acid-sodium citrate buffer solution. STZ powder 50mg prior to injection was dissolved in 5mL of buffer to prepare a 1% strength (w/v) STZ solution. The STZ solution is easy to inactivate, so it should be protected from light and prepared as it is used.

4. T2DM rat model establishment

Animals were purchased from the university of Yangzhou comparative medical center. Male Wistar rats (140-160g) of 5 weeks old were housed in animal rooms at 22. + -. 1 ℃ with a relative humidity of 50-60% and a light/dark cycle of 12h and were fed freely. Rats were acclimatized for one week and then fed with high fat diet for 3 weeks. After fasting without water deprivation for 12 hours, the rats were weighed and given an intraperitoneal injection of STZ solution at a dose of 35 mg/kg. After three days, fasting is carried out for 12h, the blood sugar of the rat is measured and recorded by a blood sugar tester, and the blood sugar value of the rat is more than or equal to 11.1mM, which indicates that the molding is successful, and is shown in figure 1A and figure B.

Grouping and administration of drugs

Blank group (C): 1mL/100g of the mixture was gavaged with double distilled water once a day for three consecutive weeks. Model group (M): 1mL/100g of the mixture was gavaged with double distilled water once a day for three consecutive weeks. Fluid increasing decoction group (ZYD): ZYD was administered at a dose of 1mL/100g by gavage at 0.8g/mL once a day for three consecutive weeks. Metformin group (Met): a25 mg/mL solution of metformin was administered once daily for three consecutive weeks by gavage at 1mL/100 g. Isodose pharmaceutical composition solution (DM): the equivalent dose of the pharmaceutical composition solution prepared in example 1 was administered once a day for three consecutive weeks by gavage at 1mL/100 g. High dose pharmaceutical composition solution (DH): the high dose pharmaceutical composition solution prepared in example 1 was administered once a day for three consecutive weeks by gavage at 1mL/100 g.

5. Experimental methods

6.1 blood glucose determination

Determination of fasting blood glucose: after the administration of the drug for 24 days, the rats are fasted for 12 hours, the tail tips are used for blood sampling, and a glucometer is used for measuring the fasting blood glucose value.

Oral glucose tolerance assay: after 3 weeks of administration to rats, fasting for 12 hours, blood glucose was measured as a 0min blood glucose level, followed by gavage administration of a 2g/kg glucose solution, blood glucose levels 15min, 30min, 60min, and 120min after glucose administration were measured, and the area under the blood glucose curve (AUC) was calculated by the trapezoidal method: AUC 0.5 × (Bg0+ Bg 30)/2 +0.5 × (Bg30+ Bg60)/2+1 × (Bg60+ Bg 120)/2.

6.2 measurement of rat body weight and food intake

The weight of the rats was recorded before the model building, and the food intake and weight of each group of rats were recorded daily after the administration.

6.3 measurement of serum Biochemical indicators

After 24 days of administration, the rat retroorbital venous plexus was bled, centrifuged at 3500rpm at room temperature for 10min, and the supernatant was collected and stored at-20 ℃. The Glycated Serum Protein (GSP), Total Cholesterol (TC), Triglyceride (TG), low density lipoprotein (LDL-C) contents of the rat sera of each group were determined according to the kit instructions.

6.4 morphological Observation of pathological tissues

Rat pancreas was removed and fixed in 4% paraformaldehyde solution, and the material was obtained conventionally, dehydrated and embedded in paraffin. Sections were HE stained and observed with an optical microscope.

6. Results of the experiment

7.1T2DM rat model establishment

The rats in the blank group were continuously fed with the normal diet for 3 weeks, the molded rats were continuously fed with the high fat diet for 3 weeks, and the weights of the two groups were statistically significantly different (p <0.01), and the molded rats had a significant increase in weight compared to the blank rats (fig. 1-a).

On the third day after the model rats were injected with STZ and the blank rats were injected with the same amount of sodium citrate buffer, fasting plasma glucose was measured for the blank and molded rats, and the model successful rats (FIG. 1-B) were selected as the model rats having a fasting plasma glucose value of 11.1mmol/L or more.

The experimental result shows that the T2DM rat model is successfully established at this time.

7.2 weight and diet changes in T2DM rats

After three weeks of administration, the body weight of rats in the other groups was reduced except the blank group; there was no significant difference in the amount of weight change of each administration group compared to the model group, and the DM group, the ZYD group, and the Met group tended to improve the weight loss (fig. 2-a).

In the aspect of food intake, the model group has obvious increase compared with the blank group, and the DM group has reduced diet compared with the model group (p < 0.05); the DH group showed no significant changes compared to the model group; the ZYD group and the Met group are both obviously improved (p is less than 0.01, and p is less than 0.001), and the specific figure is shown in figure 2-B.

The results show that the DM group can improve polyphagia symptoms of rats and slightly improve weight loss and polydipsia symptoms.

7.3 Effect on blood glucose levels in T2DM rats

The most significant clinical symptom of type 2 diabetes is elevated blood sugar. After 24 days of administration, fasting blood glucose values of rats in each group were measured (fig. 3-a), and compared with the blank group, the fasting blood glucose values of the rats in the model group were always at a high level and were statistically significantly different (p < 0.001); compared with the model group, the fasting blood glucose value of each administration group is obviously reduced (p is less than 0.01), and the DM group and the DH group have stronger blood glucose reducing effect than the ZYD group. The results show that both the DM group and the DH group have the effect of reducing the fasting blood glucose of the T2DM rats, and have more obvious effect compared with the ZYD of the whole formula.

The glycosylated serum protein and the blood sugar can both reflect the control degree of the blood sugar of the organism, and the glycosylated serum protein can reflect the average level of the blood sugar within 1-3 weeks before blood sampling, which is different from the instant blood sugar reflected by the fasting blood sugar. By measuring the content of GSP in serum (FIG. 3-B), the GSP content in the model group was significantly increased compared to that in the blank group, while the GSP content in each administration group was decreased compared to that in the model group, wherein the DM group was most significantly decreased (p < 0.001). The results show that both DM group and DH group can reduce the level of glycosylated serum protein and reduce blood sugar, and the DM group has more obvious effect than ZYD group of the whole formula.

The T2DM rat has reduced blood sugar regulating capacity due to relatively damaged islet cells or insulin resistance, and the regulating capacity of the body on blood sugar is known through an oral glucose tolerance test. Through measurement, the area under the blood glucose curve of the model group is obviously increased (p <0.001) compared with that of the blank group (figure 3-C and figure 3-D), which indicates that the blood glucose regulating capability of the model group is obviously reduced; the DM group was able to significantly reduce the area under the blood glucose curve (p <0.01) of T2DM rats, while none of the other groups of rats improved glucose tolerance. The results show that the DM group can improve the oral glucose tolerance of T2DM rats and improve the blood glucose regulating capability of T2DM rats.

7.4 Effect on blood lipid levels in T2DM rats

After 24 days of administration, the contents of TG, T-CHO and LDL-C in rat serum were measured. The results show (FIG. 4) that the model group T-CHO, TG, LDL-C were significantly elevated (p <0.001) compared to the blank group; compared with the model group, TG, T-CHO and LDL-C of the DM group, the DH group, the ZYD group and the Met group are all significantly reduced (p is less than 0.001). The results show that DM group, DH group and ZYD can reduce total cholesterol, triglyceride and low density lipoprotein of diabetic rats, regulate blood lipid disorder and improve blood lipid metabolism.

7.5 Effect on serum insulin levels in diabetic rats

After 24 days of administration, fasting serum insulin levels were determined in each group of rats. The results are shown (FIG. 5-A), where the fasting serum insulin levels were decreased in the model group compared to the blank group (p < 0.05); insulin levels were elevated in the DM, ZYD, and Met groups compared to the model group (p < 0.05). The results show that the DM group and the ZYD group can increase the serum insulin of the T2DM rats and relieve the symptom of insufficient insulin secretion.

The insulin resistance index (HOMA-IR) and insulin sensitivity index (HOMA-ISI) of rats were calculated from the fasting blood glucose level and the fasting insulin value. As a result, it was found (fig. 5-B, fig. 5-C) that the model group HOMA-IR was significantly increased (p <0.001) and the HOMA-ISI was significantly decreased (p <0.001) compared to the blank group; indicating that the model rat has an increased level of insulin resistance and a decreased insulin sensitivity; the DM group and DH group showed a significant reduction in HOMA-IR (p <0.001) and a significant increase in HOMAISI (p <0.001) compared to the model group; the ZYD group shows a significant reduction in HOMA-IR (p <0.01) and a significant increase in HOMA-ISI (p < 0.01). The results show that both DM group and DH group can improve insulin resistance level and increase insulin sensitivity of organism, and the effects are stronger than those of ZYD group and Met group.

7.6 Effect on islet histomorphology in diabetic rats

By H-E staining of pancreatic tissues (figure 6), normal rat islet tissues are distributed among acini, the periphery is clear and regular, islet cells are in a lump shape, islet cell nuclei are round, and staining is blue; the pancreatic islets of the model group are diseased, the pancreatic islets are atrophied, the cytoplasm is loose and lightly stained, exocrine glands invade the pancreatic islets, a small amount of acinar cells stretch into the pancreatic islets and are staggered with the pancreatic islet cells, the periphery between the pancreatic islets and the secretory glands disappears, and part of the pancreatic islet cells are subjected to vacuole degeneration; compared with the model group, the cell deformation degree of each administration group is reduced to different degrees, the islet cell periphery is slightly clear, and the result shows that the DM, the DH and the ZYD have a certain islet cell protection effect.

Claims (1)

1. A pharmaceutical composition for treating type 2 diabetes, said pharmaceutical composition comprising: comprises, by weight, 708.632 parts of harpagide, 207.128 parts of harpagoside, 139.352 parts of verbascoside, 116.632 parts of cinnamic acid, 11.92 parts of ferulic acid and 12.192 parts of p-coumaric acid.

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