CN113082106A

CN113082106A - Compound composition, application of compound composition in preparation of medicine for treating diabetic complications and medicine for treating diabetic complications

Info

Publication number: CN113082106A
Application number: CN202110465361.3A
Authority: CN
Inventors: 巫臻玨; 王宝民
Original assignee: Individual
Current assignee: Individual
Priority date: 2017-03-17
Filing date: 2017-03-17
Publication date: 2021-07-09
Also published as: CN106822338B; CN106822338A

Abstract

The invention discloses a compound composition, application thereof in preparing a medicament for treating diabetic complications and a medicament for treating the diabetic complications, wherein the compound composition comprises the following raw materials in percentage by weight: 20 to 75 percent of heartleaf houttuynia herb, 15 to 70 percent of peach blossom and 10 to 30 percent of amur corktree bark; the compound composition has the advantages of good curative effect and less side effect on treating the diabetic complications, and can be used for preparing the medicines for treating the diabetic complications.

Description

Compound composition, application of compound composition in preparation of medicine for treating diabetic complications and medicine for treating diabetic complications

The invention is a divisional application of Chinese patent application with application date of 2017, 3 and 17, application number of 2017101635509, named as 'Compound composition for reducing blood sugar and blood lipid, and preventing and/or treating diabetes and complications thereof' and application thereof.

Technical Field

The invention relates to a compound composition for reducing blood sugar and blood fat and preventing and/or treating diabetes and complications thereof, and application thereof in preparing a medicine or a health-care product for reducing blood sugar and blood fat and preventing and/or treating diabetes and complications thereof, in particular to a compound composition, application thereof in preparing a medicine for treating diabetes complications and a medicine for treating diabetes complications.

Background

Diabetes (diabetes) is a series of metabolic disorder syndromes of sugar, protein, fat, water, electrolyte and the like caused by hypofunction of pancreatic islets, insulin resistance and the like due to the action of various pathogenic factors such as genetic factors, immune dysfunction, microbial infection and toxins thereof, free radical toxins, mental factors and the like on organisms, and is clinically characterized by hyperglycemia.

Diabetes mainly includes type 1 diabetes and type 2 diabetes, wherein the proportion of type 2 diabetes in diabetic patients is about 95%, and type 2 diabetes is increasingly advanced and younger with the improvement of living standard and the change of life style. Because blood sugar is continuously increased, the blood sugar causes the metabolic disturbance of the whole body, and the latent property causes the chronic complications of multiple tissues and organs such as heart, blood vessels, kidney, nerves and the like, so that the life is threatened due to the functional failure.

In the prior art, the medicines for treating diabetes mainly comprise western medicines and some Chinese and western medicine compound preparations. Although these drugs are effective in lowering blood sugar, their use is severely limited because prolonged use can cause damage to the body. Pharmaceutical preparations for the treatment of diabetes are also currently available, which, although capable of reducing blood glucose to some extent, are still of limited therapeutic value. The invention provides a basis for developing the different drugs into novel hypoglycemic drugs by reasonably combining the different drugs and deeply researching the hypoglycemic drugs and other important effects by means of mathematical methods such as statistical principles, uniform design and the like.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides the application of the compound composition with remarkable effect in preparing the medicine for treating the diabetic complications.

The invention also provides a medicament for treating diabetic complications.

The invention also provides a compound composition for treating diabetic complications.

In order to solve the technical problems, the invention adopts a technical scheme that:

a compound composition for reducing blood sugar and blood fat, and preventing and/or treating diabetes and its complications comprises (by weight) herba Houttuyniae 20-75%, flos persicae 15-70%, and cortex Phellodendri 10-30%.

Preferably, the compound composition is a mixture of the extracts of the raw materials, the extracts of the raw materials are obtained by extracting the raw materials with a solvent, the process can be implemented by adopting a method and conditions which are conventional in the field of drug extraction, the solvent for extraction can be those which are commonly used, such as alcohol solvents like water and ethanol, acetone, etc., the extraction temperature can be, for example, 45 ℃ to 100 ℃, and the extraction temperature is not particularly limited. According to a specific aspect of the invention, the solvent is one or more selected from water, methanol, ethanol and acetone. In one embodiment, the solvent is an ethanol aqueous solution with a volume fraction of 30% to 80%.

According to the invention, the extract of the raw material may be in liquid form (when the vehicle is water) or in solid form. According to a preferred aspect of the present invention, the extract of the raw material is in a solid form, and the solid form is prepared by subjecting the extract in a liquid form to vacuum drying, spray drying or microwave drying. The extract can be a primary extract or an extract obtained by further separating the primary extract to retain the active ingredients.

According to the invention, the compound composition can further comprise other active substances with the functions of reducing blood sugar and blood fat, and preventing and/or treating diabetes and complications thereof besides the houttuynia cordata, the peach blossom and the phellodendron. The active substances may be those known in the art, such as the biguanide drug metformin or the thiazolidinedione drug pioglitazone or the Glut2 inhibitor canagliflozin, etc., such as morous alba and other crude extracts, etc.

The invention adopts another technical scheme that: a preparation method of the compound composition for reducing blood sugar and blood fat and preventing and/or treating diabetes and complications thereof comprises the steps of respectively extracting houttuynia cordata, peach blossom and golden cypress by adopting solvents to obtain respective extracting solutions, then mixing the extracting solutions, and drying to obtain the composition; or mixing the raw materials of the houttuynia cordata, the peach blossom and the phellodendron, extracting by adopting a solvent, and spray drying an extracting solution to prepare the composition.

Further, the above method can be carried out by using a method and conditions which are conventional in the field of extraction of medicinal materials, and the solvent for extraction can be those commonly used, such as water, alcohol solvents such as ethanol, acetone, etc., and the extraction temperature can be, for example, 45 ℃ to 100 ℃, without particular limitation. According to a specific aspect of the invention, the solvent is one or more selected from water, methanol, ethanol and acetone. In one embodiment, the solvent is an ethanol aqueous solution with a volume fraction of 30% to 80%.

According to the present invention, the drying method may be vacuum drying, spray drying, microwave drying, or the like, and is not particularly limited.

The invention also relates to the application of the compound composition for reducing blood sugar and blood fat and preventing and/or treating diabetes and complications thereof in preparing medicines for reducing blood sugar and blood fat and preventing and/or treating diabetes and complications thereof.

The invention also relates to the application of the compound composition for reducing blood sugar and blood fat and preventing and/or treating diabetes and complications thereof in the auxiliary preparation of health-care products for reducing blood sugar and blood fat and preventing diabetes and complications thereof.

The medicine or health care product of the invention is various types of preparations which are generally prepared from the compound composition of the invention and pharmaceutically acceptable medicine carriers. Wherein, the carrier refers to any drug carrier which is selected and used for meeting the preparation requirement in the pharmacy field, and comprises diluents such as starch, dextrin, microcrystalline cellulose and the like; humectants such as water, glycerin, polyvinylpyrrolidone, etc.; and lubricants such as magnesium stearate, colloidal silica, etc. Preferably, the medicine or health care product is an oral preparation, and further, the oral preparation can be capsules, tablets, pills, granules, powder, liquid preparations, sustained-release preparations and the like.

The medicine or health product of the invention not only can comprise the compound composition of the invention, but also can comprise other active substances for reducing blood sugar and blood fat without reducing the efficacy of the compound composition, and the other active substances can be those known in the art, such as biguanide, metformin, thiazolidinedione, pioglitazone, Glut2 inhibitor canagliflozin, and the like, such as mulberry and other crude extracts. Thus, hyperlipidemia, diabetes mellitus and complications thereof and other associated metabolic diseases can be synergistically treated from different links of action and different mechanisms of action.

Experiments prove that the compound composition has good effect on treating diabetes, particularly type 2 diabetes. It will be appreciated by those of ordinary skill in the art that the dosage administered for treatment will depend on a variety of factors including the nature and severity of the associated condition, the age, weight and individual response of the patient, the route of administration and the number of administrations. Dosage administration may be in single dose form or in multiple dose form. The dosage and administration regimen for a particular individual depends on the symptoms and the condition of the patient and can be adjusted by the physician to suit particular needs.

Due to the implementation of the technical scheme, compared with the prior art, the invention has the following advantages:

the compound composition of the invention combines the heartleaf houttuynia herb, the peach blossom and the amur corktree bark according to a specific proportion, obtains a synergistic interaction effect, not only maintains the basic beneficial effects of each medicinal material in the combination, stably reduces the blood sugar, complements the advantages, but also obviously reduces the potential damage possibly brought by long-term administration or high-dose administration of a single medicinal material. The compound composition can be used for promoting islet tissue repair, gradually recovering islet functions, gradually correcting metabolic disorders, inhibiting series metabolic disorders caused by hyperglycemia and hyperlipidemia, inhibiting micro inflammation and inhibiting diabetic cardiovascular complications, and can be used for preparing medicines for preventing and/or treating diabetes and complications thereof or assisting in preparing health-care products for preventing and/or treating diabetes and complications thereof.

Drawings

FIG. 1 is a graph showing the results of pathological examination of aorta in example 6, wherein A: a normal control group; b: a model control group; c: composition four high dose group; d: composition four low dose group; e: zhibituo group.

Detailed Description

Research shows that the houttuynia cordata has definite antibacterial, antiviral and anti-inflammatory effects and can also improve lipid metabolism of diabetes. The houttuynia cordata contains various phenolic substances, has an anti-injury effect on different harmful substances, and is also commonly used for treating kidney diseases; cortex Phellodendri has antibacterial, blood pressure lowering, antiulcer, immunity suppressing and blood sugar lowering effects, and cortex Phellodendri alkaloid has effects of resisting heart failure, lowering blood pressure, protecting blood vessel endothelium, and protecting cardiovascular system. The modern researches show that peach blossom flavones and polysaccharides have obvious antioxidant activity and have good inhibition effect on tissue damage caused by oxidative stress, and the peach blossom flavones can also regulate the functions of the central nervous system, improve the functions of the nervous system and regulate the glycometabolism. The three components are organically combined to achieve the practical and effective treatment of diabetes and various complications of the diabetes, such as cardiovascular diseases, kidney diseases, nerves diseases and the like.

The invention scientifically combines and matches the medicinal materials by means of related mathematical research methods and application, embodies the characteristics and advantages of combination, brings out the best in prevention and treatment of diabetes and metabolic diseases related to diabetes, and better avoids respective adverse effects or weaknesses.

Compared with the prior art, the invention has the following advantages:

1) the basic beneficial effects of all medicinal materials in the composition are kept, the blood sugar is stably reduced, the advantages are complementary, and the potential damage caused by long-term administration or high-dose administration of single medicinal material is obviously reduced.

2) Promote the repair of islet tissues and gradually recover the islet function,

3) gradually correcting metabolic disorder, inhibiting series metabolic disorder caused by hyperglycemia and hyperlipemia, inhibiting micro inflammation, and inhibiting diabetic cardiovascular complication.

The present invention will be described in further detail below with reference to specific examples, but the present invention is not limited to these examples.

EXAMPLE I Effect of different compositions of ethanol extracts on blood glucose and triglycerides in Normal mice

1. The tested medicinal materials: herba Houttuyniae (houttuynia cordata Thunb.) of Oriental houttuynia is identified as dried aerial part of plant of houttuynia of Saururaceae; cortex Phellodendri, originated from Sichuan, and identified as dried bark of plant of genus phellodendron of family Rutaceae; the peach blossom is originated from Shandong, and is identified as a flower of a plant of the genus Prunus of the family Rosaceae.

2. Consists of the following components:

the combination is as follows: 75% of houttuynia cordata, 15% of peach blossom and 10% of golden cypress;

combining two: 40% of houttuynia cordata, 30% of peach blossom and 30% of golden cypress;

combining three components: 20% of houttuynia cordata, 70% of peach blossom and 10% of golden cypress.

And (4) combining: 44% of houttuynia cordata, 38% of peach blossom and 18% of golden cypress.

3. Preparing a test medicament: the above components are taken according to the weight percentage ratio, 200g of the components are respectively taken, 60% ethanol is used as a solvent, the material liquid ratio is firstly extracted for 1:15, and secondly extracted for 1:10, reflux extraction is carried out for 2 times at 80 ℃, each time is 1 hour, the ethanol is recovered and concentrated to 1g/ml (according to the total amount of crude drugs), and the mixture is frozen for standby application, and is properly diluted to the application concentration by distilled water when in use.

4. And (3) effect measurement: normal ICR mice, 18-20g, female and male, after being adaptively raised for three days, were randomly divided into groups (10 groups/group, female and male half) as shown in table 5 as required, and fed with high-sugar high-fat diet (8% sucrose, 15% lard, 0.5% cholesterol, 0.25% sodium cholate were added in conventional diet processing), administration was started (8g/kg body weight, based on the total amount of crude drugs, gavage administration was performed; a blank control group was given with equal volume of distilled water, 0.1ml/10g), once a day, administration was performed 19 days later, fasting was performed next day through the orbital venous plexus of mice, fasting blood glucose and blood lipid levels of mice were detected, conventional administration and glucose load (2g/kg, ig) were performed, blood was taken through the orbital plexus of mice, and blood glucose and fasting triglyceride were respectively detected at different time points before and after serum glucose load. The results show that the combinations have obvious inhibition effects on fasting plasma lipid and postprandial blood glucose increase of normal mice, but the action characteristics have certain differences, which are shown in table 1.

TABLE 1 influence of ethanol extracts of different compositions on blood glucose and triglycerides in normal mice (mean + -SEM)

n 10, P <0.05, P <0.01, compared to the blank.

EXAMPLE II Effect of ethanol extracts of different compositions on blood glucose and triglycerides in alloxan diabetic mice

Referring to the composition and extraction method of example one, each combined concentrate was prepared in the same amount and frozen for use. An additional set of experiments was combined drug group (combination two + p): the combination two was administered in combination with 10mg/kg pioglitazone.

And (3) effect measurement: normal ICR mice, 22-26g, male, were acclimatized for three days, then fed on high-fat diet for one week, 12 hours on an empty stomach, and 55mg/kg of alloxan (Sigma, alloxan, Lot & Filling code: 143780112609058) was intravenously injected, and after 72 hours, oral glucose tolerance test (2g/kg, ig) was performed, and mice with glucose load of 2h and blood glucose of 11mmol/L or more were randomly divided into 6 groups (10 groups/group) as required. Each group was dosed as required (see example one, 8g/kg, ig), the model control group was dosed with equal volume of distilled water once a day, fasted the night for 19 days, bled via orbital venous plexus of mice the next day, fasting blood glucose and triglycerides of mice were measured, glucose load (2g/kg, ig) was dosed routinely and given, and blood glucose changes at various time points after glucose load were measured. The results show that the combination has good inhibition effect on fasting blood glucose, blood fat and postprandial blood glucose increase of alloxan diabetic mice, and the inhibition effect is shown in table 2.

TABLE 2 influence of ethanol extracts of different compositions on blood glucose and triglycerides (mean + -SEM) in alloxan diabetic mice

The combination one and the combination four n is 9, the rest n is 10; p <0.05, P <0.01 compared to model controls.

EXAMPLE III Effect of Water extracts of different compositions on blood glucose and triglycerides in alloxan diabetic mice

And (3) performing reflux extraction on the mixture liquid by using water as a solvent at the ratio of 1:15 for the first time and 1:10 for the second time at 90 ℃ for 2 times, 1 hour each time, and preparing compound concentrated solutions in the same amount for freezing for later use.

An additional set of experiments was combined drug group (combination two + p): the combination two was administered in combination with 10mg/kg pioglitazone.

Taking ICR mice, alloxan diabetic mice were prepared according to the method of example two, and the glucose load (2g/kg, ig)2h of the mice with blood glucose of 11mmol/L or more were randomly divided into 6 groups (10 mice/group) as follows. Each group was dosed as required (see example two, 0.1ml/10g, ig), the model control group was dosed with distilled water of equal volume once a day, fasted the night for 19 days, bled the next day via orbital venous plexus of mice to test mice for fasting glucose and triglycerides, dosed routinely with glucose load (2g/kg, ig), and tested for changes in glucose at various time points after glucose load. The results show that the combined water extracts also have good inhibition effect on fasting blood glucose, blood fat and postprandial blood glucose increase of alloxan diabetic mice, and the inhibition effect is shown in table 3.

TABLE 3 Effect of water extracts of different compositions on blood glucose and triglycerides (mean + -SEM) in alloxan diabetic mice

n 10, P <0.05, P <0.01, compared to model controls.

Example four, combination four and the effect of different combinations of the medicinal materials on alloxan diabetic mice are compared

1. Preparing a composition tetra concentrate according to the first embodiment; in addition, series of control (group 4-group 9) concentrates were prepared in the same manner, and the compositions of the series of controls are described in Table 4.

2. ICR mice are taken, alloxan diabetes mice are prepared in the same way as in example II, and the mice with glucose load (2g/kg, ig) for 2h and blood sugar more than or equal to 11mmol/L are randomly divided into the following 1-9 groups (10 mice/group) according to requirements. Each group was dosed as required (0.1ml/10g body weight, ig), once a day, model control group was dosed with equal volume of distilled water, fasting was performed the night for 19 days, blood was taken via orbital venous plexus of mice the next day, fasting blood glucose and blood lipid of mice were measured, dosed routinely and given glucose load (2g/kg, ig), as above, blood glucose change was measured at each time point. Fasting is carried out at night after 24 days of administration, blood is taken the next day to measure serum beta 2-microglobulin (beta 2-microglobulin radioimmunoassay kit, Beijing northern biotechnological research institute Co., Ltd.), NLRP3, BTC, GLP-1, PYY and glycated serum protein (NLRP3ELISA kit, BTC ELISA kit, GLP-1ELISA kit, PYYELISA kit, Nanjing Yutong biotech Co., Ltd.; glycated serum protein kit, Nanjing Biotech Co., Ltd.).

3. The result shows that the combination of the four has good inhibition effect on the increase of fasting blood sugar, postprandial blood sugar and fasting blood fat of the hyperglycemic mouse; the independent application of the houttuynia cordata has no obvious influence on blood sugar; the phellodendron bark is applied independently, has obviously weaker effect on fasting blood sugar and postprandial blood sugar than the composition IV, and has no obvious influence on triglyceride; the effects of peach blossom, houttuynia/peach blossom combination, houttuynia/phellodendron combination or peach blossom/phellodendron combination on fasting blood sugar, postprandial blood sugar and triglyceride are obviously weaker than those of the combination IV. The combination IV can effectively inhibit the increase of blood sugar and blood fat, and is shown in Table 4.

TABLE 4 comparison of the Effect of combination four and different combinations of the herbs on alloxan diabetic mice

(mean ± SEM, mmol/L) vs blank control, # P <0.05, # P < 0.01;

in comparison with the 2 sets of data,^aP<0.05，^bP<0.01, compared to the 3 groups,^cP<0.05。

and II, injecting: table n indicates the number of mice surviving each group 20 days after administration.

And II, injecting: 1. model control (distilled water 0.1ml/10 g); 2. combined four high dose (10g/kg, in crude drug)

3. Four low doses (5g/kg) were combined; 4. 4.6g/kg of peach blossom and 5.4g/kg of houttuynia cordata; 5. 7g/kg of houttuynia cordata and 3g/kg of phellodendron amurense; 6. 6.8g/kg of peach blossom and 3.2g/kg of phellodendron; 7. the houttuynia cordata is 10 g/kg; 8. 10g/kg of peach blossom; 9. 10g/kg of phellodendron bark

The presence of diabetic renal injury is indicated by the relatively high or low concentration of beta 2-microglobulin. The test results show that the high-temperature-resistant steel,

the combination of the four high and low dose groups and the peach and fish combination group can obviously reduce the serum beta 2-microglobulin, and the houttuynia cordata has the effect of reducing and indicates that the composition has a certain improvement effect on diabetic nephropathy.

The NLRP3 inflammasome is a molecular switch for regulating inflammation generation, participates in noninfectious inflammatory reaction in a plurality of chronic diseases, is closely related to diabetes micro inflammation, atherosclerosis and the like, and can generate IL-1 beta dependently by the NLRP3 inflammasome of pancreatic tissues to cause continuous damage to islet cells. Test results show that the combination of the four high-dose group and the four low-dose group, the peach and fish combination group and the houttuynia cordata group have a relatively obvious inhibiting effect on the increase of the concentration of serum NLRP3 inflammatory corpuscle, and the effects of reducing the damage to islet tissues caused by inflammation and protecting normal tissue structures and functions of the islets are prompted.

Betacellulin (BTC) regulates the growth or differentiation of a variety of different pancreatic secretory precursor cells, converts different types of precursor cells into insulin secretory cells, and increases islet beta cell numbers. Has important significance for improving the tissue structure and the function of the pancreatic islet of a diabetic patient, improving the sensitivity of peripheral tissues to insulin and maintaining the blood sugar of the patient at a stable level. Test results show that only four high-dose and low-dose groups are combined to have a relatively obvious enhancement effect on the generation of the beta-cell, and other groups have no obvious influence, so that the combination of four groups has a good treatment value on the recovery of diabetes, and the table 5 shows that the combination of four groups has a good treatment value.

TABLE 5 comparison of the Effect of combination four and different combinations of the drugs on alloxan diabetic mice (mean + -SEM, mmol/L)

Note: table n indicates the number of mice surviving each group 25 days after administration. Compared with the control of the model, the method has the advantages that,

*P<0.05，

p < 0.01; compared with group 2, a: P <0.05, b: P < 0.01.

In addition, the four high and low doses of the composition have good regulating effect on the intestinal hormones, particularly the concentration of serum GLP-1 is obviously improved, and other groups have certain effect but are not obvious. The combination of four high and low doses can also obviously reduce the serum uric acid level, and the combination also has certain benefits for other metabolic abnormality diseases. Each group had no significant effect on the action of PYY. See table 6.

TABLE 6 comparison of the Effect of combination four and different combinations of the drugs on alloxan diabetic mice (mean + -SEM, mmol/L)

Note: table n indicates the number of mice surviving each group 25 days after administration.

P <0.05, P <0.01 compared to model controls.

Example five, the effect of combination of four and other herbs on the liver and kidney function of normal mice

Referring to example four, a combined tetra concentrate and series of control concentrates were prepared for use (see Table 7 for details of compositions)

And (3) effect measurement: normal ICR mice, 18-20g, female and male, after being adaptively raised for three days, are randomly divided into groups (10 groups/group, female and male half) as shown in the table 7 according to requirements, each group starts to be administrated according to the requirements (a blank control group is administrated with distilled water with the same volume), the administration is carried out once a day for 20 days continuously, the administration is carried out after 12 hours of fasting, eyeballs are picked for blood sampling, serum is prepared conventionally, and related indexes of liver and kidney functions of the mice are detected, and the related indexes are shown in the table 7.

The results show that: under the experimental condition, compared with a blank control, the combination of the golden cypress and the golden cypress/peach blossom has potential influence on the liver and kidney functions, particularly the inhibition effect of the golden cypress on serum albumin (Alb.) is obvious, the combination of four high and low doses has no obvious influence on the liver and kidney functions, and each group of other medicines has no obvious influence compared with the blank control. The combination of the three medicinal materials in proper proportion can not obviously change the safety of the combination.

TABLE 7 Effect of combination of group IV and other herbs on liver and kidney function in Normal mice (mean + -SEM)

Note one: except phellodendron bark, n is 9 and the rest n is 10. P <0.05, P <0.01 compared to the blank control.

3. Four low doses (5g/kg) were combined; 4. 3.2g/kg of phellodendron and 6.8g/kg of peach blossom; 5. 7g/kg of houttuynia cordata and 3g/kg of phellodendron amurense; 6. 5.4g/kg of houttuynia cordata and 4.6g/kg of peach blossom; 7. 10g/kg of phellodendron amurense.

In view of the comparison of the different effects, including the comprehensive effects on blood sugar, triglyceride, glycated serum protein, serum beta-2 microglobulin, inflammatosome NLRP3, beta-cytomin and the like, the main effects of the heartleaf houttuynia herb, the amur corktree bark and the peach blossom are obviously enhanced and have outstanding advantages compared with the single or other combined application of each medicinal material by combining the heartleaf houttuynia herb, the amur corktree bark and the peach blossom in a proper proportion, and the toxicity of the combined medicine is not obviously increased, thereby prompting that the clinical potential therapeutic effect of the combined medicine has advantages.

EXAMPLE six, Effect of combination of four on quail Atherosclerosis

Referring to example one, a combined tetra concentrate was prepared and frozen for use.

Male Korean black feather quails, 5 weeks old, 46, 90-110g, after adaptive feeding for 3d, 6 were randomly selected and continued to be used as normal control with ordinary feed, and the rest were fed with high-fat feed for 30 days (2 times per day with each feed being about 16-20 g/day). Fasting for 12h, collecting blood from pterygoid vein, separating serum to measure Triglyceride (TG) content, and randomly dividing into 5 groups of 8 individuals according to the principle of approximate TG value.

1) A normal control group; 2) high fat control group; 3) the four high dose groups were combined at 6 g/kg; 4) the four low dose groups were combined at 3 g/kg; 5) lipitor group 400mg/kg (suspended with 0.5% CMC-Na).

The groups were administered with the corresponding drugs by intragastric administration at a dose per day, and the normal control group and the high-fat group were administered with a vehicle (0.5% CMC-Na,0.5ml/100g, ig) at a relative volume, and the administration amount was adjusted according to the body weight, during which high-fat diet feeding was continued.

Each group was continuously administered by gavage for 30 days, fasted for 12h, blood was taken from jugular vein, serum was separated conventionally, and Triglyceride (TG), Total Cholesterol (TC), High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL) concentrations in serum were measured (each purchased from Zhongsheng North China Biotechnology Ltd.). The aorta is taken after blood collection, and is preserved by 10% neutral formaldehyde for pathological observation.

As a result, the compound extract reduced TG, TC and LDL in serum and increased HDL/LDL ratio in different degrees in both high and low doses relative to the model group, and zhibituo significantly reduced TC, TG and LDL, as shown in Table 8.

TABLE 8 Effect of combination four on atherosclerotic quail blood lipids (mean + -SEM, mmol)

P compared to normal group<0.01; in comparison with the set of models,^*P<0.05。

referring to fig. 1, the aorta pathological examination shows that the quail aorta intima of the normal control group occasionally has a small amount of lipid, and has no obvious lesions such as intimal thickening, endothelial swelling and the like, the quail aorta intima of the model group is thickened, endothelial swelling and hyperplasia and subendothelial lipid deposition, and the intima lipid deposition is obvious around part of the artery wall or most of the area, and foam cells are visible. Compared with quail aortic lesions in a model group, the composition four extracts can reduce arterial wall lipid deposition, intimal lesions and foam cells, and the effects of the composition four high and low dose groups are similar, so that the composition has potential inhibition effect on diabetic vascular complications, the aortic lipid deposition degree of the zhibituo group is relatively low, and most of intimal lesions are slight or mild.

EXAMPLE seven

A compound composition for reducing blood sugar and blood fat, and preventing and/or treating diabetes and complications thereof can be obtained by the following method: taking 200ml of the concentrated solution obtained in the example 4, and placing the concentrated solution under the vacuum drying condition of 0.1MP under negative pressure, 75 ℃ and 24 hours to obtain about 45.6-47.65 g of dry extract (extractum), wherein the drying method can also adopt spray drying, microwave drying and the like. The compound composition can be used as a health-care product for reducing blood sugar and blood fat and preventing diabetes and complications thereof.

Example eight

A pharmaceutical formulation, which is a tablet, which can be prepared by the following process: taking 15g of the compound composition obtained in the first step, adding 6g of compressible starch and 4g of dextrin, uniformly mixing, performing wet granulation by adopting 40% ethanol, cooling to below 60 ℃, drying, granulating, adding 0.6g of talcum powder, uniformly mixing, and pressing into 100 tablets, wherein the content of the compound composition is 0.15 g/tablet.

The pharmaceutical preparation of the embodiment can be used for reducing blood sugar and blood fat and preventing/treating diabetes and complications thereof.

Example nine

A pharmaceutical preparation, which is an oral liquid, can be prepared by the following method: taking 5g of the compound composition obtained in the three combinations of two in the example, dissolving in 400ml of distilled water, preparing a solution, partially decoloring by using activated carbon, filtering, adding distilled water to prepare 500ml of 1% aqueous solution, filtering by using a microporous filter membrane (phi 0.450 mu m), sterilizing, performing sterile subpackage with 10ml of each bottle, and sealing.

Example ten

A compound preparation of the compound composition and metformin can be prepared by the following steps: taking 10g of the compound composition obtained in the second combination of the embodiment, 10g of metformin, 5g of dextrin and 15g of microcrystalline cellulose, uniformly mixing, adopting a 50% ethanol wet method to granulate, cooling to below 60 ℃, drying, granulating, adding 0.4g of magnesium stearate, uniformly mixing, and filling 100 capsules, wherein each capsule contains 0.1g of extract and 0.1g of metformin on average. The pharmaceutical preparation of the embodiment can be used for reducing blood sugar and blood fat and preventing/treating diabetes and complications thereof.

The present invention has been described in detail in order to enable those skilled in the art to understand the invention and to practice it, and it is intended that all equivalent changes and modifications made according to the spirit of the present invention be included in the scope of the present invention.

Claims

1. The application of a compound composition in preparing a medicament for treating diabetic complications is characterized in that the compound composition comprises the following raw materials in percentage by weight: 20 to 75 percent of heartleaf houttuynia herb, 15 to 70 percent of peach blossom and 10 to 30 percent of amur corktree bark.

2. The use of the compound composition of claim 1 in the preparation of a medicament for treating diabetic complications, wherein the compound composition is a mixture of extracts of the raw materials, and the extracts of the raw materials are extracts obtained by extracting the raw materials with a solvent.

3. The use of the compound composition according to claim 2 in the preparation of a medicament for the treatment of diabetic complications, wherein the vehicle is a combination of one or more selected from water, methanol, ethanol, and acetone.

4. The use of the compound composition according to claim 2 in the preparation of a medicament for the treatment of diabetic complications, wherein the solvent is an aqueous ethanol solution with a volume fraction of 30-80%.

5. The use of a combination according to claim 2 in the manufacture of a medicament for the treatment of diabetic complications, wherein the extract of the raw material is in liquid or solid form.

6. The use of a combination according to claim 5 in the manufacture of a medicament for the treatment of diabetic complications, wherein the extract of the raw material is in solid form and the solid form is prepared by vacuum drying, spray drying or microwave drying the extract in liquid form.

7. The use of the combination composition of claim 1 in the preparation of a medicament for the treatment of diabetic complications, wherein the combination composition is prepared by the following method: respectively extracting the houttuynia cordata, the peach blossom and the phellodendron by adopting a solvent to obtain respective extracting solutions, then mixing the extracting solutions, and drying to obtain the compound composition; or mixing the raw materials of the houttuynia cordata, the peach blossom and the phellodendron, extracting by adopting a solvent, and drying an extracting solution to prepare the compound composition;

wherein the solvent is one or more selected from water, methanol, ethanol and acetone, and the extraction temperature is 45-100 ℃.

8. The use of the compound composition according to claim 1 for preparing a medicament for treating diabetic complications, wherein the compound composition further comprises active substances for treating diabetic complications except for the houttuynia cordata, the peach blossom and the phellodendron amurense.

9. A medicament for treating diabetic complications, which comprises the compound composition as claimed in any one of claims 1 to 8, a pharmaceutically acceptable pharmaceutical carrier, and optionally an active substance other than the houttuynia cordata, peach blossom and phellodendron amurense for treating diabetic complications.

10. A combination composition as claimed in any one of claims 1 to 8 for use in the treatment of diabetic complications.