CN1327876C - Chinese medicinal composition for treating diabetes and its complications - Google Patents

Abstract

A medicinal composition for treating or preventing diabetes or its complications is characterized by comprising medicines for nourishing yin, invigorating qi, promoting blood circulation, cooling blood, astringing, promoting diuresis and/or their extracts, etc.

Description

Traditional Chinese medicine composition for treating diabetes and its complications

technical field

The invention relates to a medicine for treating diabetes and its complications, more specifically, the invention relates to a new composition of traditional Chinese medicine or its extract for treating diabetes and diabetic retinopathy and a preparation method thereof.

Background technique

Diabetes mellitus is a syndrome caused by an absolute or relative decrease in insulin secretion and/or insulin action. Due to the clinical manifestations of excessive drinking and eating but gradually losing weight, Chinese medicine also calls it diabetes. Its clinical manifestation is hyperglycemia, accompanied by hyperuricemia, which is the origin of the name diabetes. According to the classification of modern medicine, diabetes is divided into two categories: insulin-dependent diabetes (type I diabetes) and non-insulin-dependent diabetes (type II diabetes).

With the progress of research, the drugs used to treat diabetes itself, including the use of insulin, make high blood sugar no longer threaten the life safety of patients. However, due to the long duration of diabetes, long-term diabetic complications have become the cause of affecting the quality of life of diabetic patients and threatening the lives of diabetic patients.

According to the data published by the World Health Organization (WHO) Diabetes Committee in 2002, the number of diabetic patients in the world is close to 200 million, and about 96% of them will die due to chronic complications. It is also reported that the number of diabetic patients in China has exceeded 50 million. With the acceleration of industrialization, the number of patients is on the rise.

Diabetic retinopathy is a common complication of diabetes, its incidence accounts for about 50% of diabetic patients, and the blinding rate reaches 6-8%. According to statistics, 7% of those with a history of diabetes for 10 years have retinopathy, about 25% for 15 years, and 63% for more than 15 years. The pathological basis of diabetic retinopathy is microvascular disease, that is, diabetes causes changes in the vascular permeability of the retina, resulting in severe vision loss and blindness.

In the past, in order to treat diabetic retinopathy, the methods used mainly include the application of drugs that regulate vascular permeability or laser surgery. However, there is no medicine with particularly good curative effect so far, and surgical treatment is only effective in the early stage of the disease.

For diabetic retinopathy, traditional Chinese medicine has also carried out a lot of research, put forward some prescriptions, and the effect is better to a certain extent, for example: ① Syndrome differentiation and treatment: There are mainly nourishing yin and clearing heat, using Zhuye Huangqi Decoction (Astragalus root, Rehmannia glutinosa, Ophiopogon japonicus, angelica, chuanxiong, licorice, scutellaria baicalensis, gypsum, peony, ginseng), white tiger plus ginseng soup (gypsum, Anemarrhena, japonica rice, licorice, ginseng); some are mainly for nourishing yin and tonifying kidney, using Qiju Dihuang Decoction (Rehmannia glutinosa, yam, cornus, medlar, Poria cocos, Moutan bark, Alisma, chrysanthemum), Liuwei Dihuang Decoction (rehmannia glutinosa, dogwood, yam, Alisma, Poria, paeonol); Mainly, use Taohong Siwu Decoction (peach kernel, safflower, rehmannia glutinosa, angelica, red peony root, Chuanxiong, etc.), for promoting blood circulation and removing blood stasis. ②Treatment with special prescriptions: such as Zhu Chenyu's "Tangyanming" prescription, He's "Huoxuehuayuling" and so on. ③Acupuncture treatment: For example, Wu's family uses Pishu, Jingming, Geshu, Zusanli, and Qiuhou as the main points, and uses appropriate acupoints to achieve good curative effect. However, the above prescriptions are all clinical prescriptions, with many retrospective summaries and few prospective studies, and most of them lack positive controls, so the curative effects are not comparable. Among them, there are many clinical studies and few experimental studies, and the mechanism of efficacy is unknown. Not only for diabetic retinopathy, but also for other diabetic complications, and it is doubtful whether its effect can be widely promoted.

Therefore, the current status is that there is no satisfactory therapeutic drug mainly for the treatment of diabetic retinopathy.

The object of the present invention is just this. The object of the present invention is to provide a composition of traditional Chinese medicine for treating diabetic retinopathy or its extract and its preparation method.

Contents of the invention

The inventors of the present invention, on the basis of previous prescriptions and treatment ideas for the treatment of diabetic complications, through long-term in-depth research, found that on the basis of the existing proven prescriptions Erzhi Wan and Liuwei Dihuang Wan, the prescription was improved, and the result was found to contain at least The composition composed of yin-tonifying, qi-tonifying, blood-activating, cooling-blood, diuretic and diuretic drugs or their extracts has outstanding curative effect on treating or alleviating diabetic complications, thus completing the present invention.

Therefore, the present invention relates to a medicine for treating diabetic complications, more specifically, the present invention relates to a new Chinese medicine for treating diabetic retinopathy or a composition of its extract and a preparation method thereof, which has the following composition:

1. A pharmaceutical composition for treating diabetes or its complications, characterized in that it contains medicines for nourishing yin, nourishing qi, promoting blood circulation, cooling blood, diuresis and/or their extracts.

2. The composition of the above 1, wherein the complication of diabetes is diabetic retinopathy.

3. The composition of the above-mentioned 1 or 2, characterized in that the above-mentioned yin-tonifying medicine is selected from Asparagus, Dendrobium, Polygonatum Polygonatum, Polygonatum, Lily, Lycium barbarum, Mulberry, Eclipta chinensis, Ligustrum lucidum, Tremella fungus, Cornus officinalis;

Qi-invigorating medicines are selected from ginseng, codonopsis, heterophylla, astragalus, atractylodes macrocephala, yam, white lentils, and licorice:

Blood-promoting drugs are selected from Chuanxiong, Corydalis, Turmeric, Sanleng, Salvia, Polygonum cuspidatum, peach kernel, safflower, Achyranthes bidentata, Panax notoginseng;

The heat-clearing medicine is selected from gypsum, reed root, gardenia, scutellaria, coptis, cortex, rehmannia, scrophulariae, moutan bark, red peony root, and honeysuckle;

The water diuretic drugs are selected from Poria, Polyporus, Alisma, Akebia, Yinchen, Chixiaodou, Corn Silk, and Red Smilax Poria.

4. The composition of the above-mentioned 1 or 2 is characterized in that it contains Ligustrum lucidum, Cornus officinalis, Salvia miltiorrhiza, Alisma, Moutan bark, Panax notoginseng, Eclipta chinensis, Chinese yam, Poria cocos, Achyranthes bidentata, Red soil Poria cocos and/or their extracts thing.

5. The composition of the above-mentioned 1 or 2, based on the crude drug, is composed of 20-50 parts by weight of yin-tonifying medicine, 10-30 parts by weight of qi-tonifying medicine, 10-40 parts by weight of blood-activating medicine, 5-20 parts by weight of Heat-clearing and blood-cooling medicine and 20-50 parts by weight of diuretic medicine.

6. The composition of the above-mentioned 1 or 2, based on the crude drug, is composed of 25-45 parts by weight of yin-tonifying medicine, 10-20 parts by weight of qi-tonifying medicine, 15-35 parts by weight of blood-activating medicine, 5-10 parts by weight of Heat-clearing and blood-cooling medicine and 20-40 parts by weight of diuretic medicine.

7. The composition of any one of the above-mentioned 1-6, wherein the weight ratio of each component or each component raw material is:

Ligustrum lucidum 15 parts Eclipta 12 parts Dogwood 12 parts

Yam 15 parts Danshen 12 parts Three Seven 6 parts

Moutan bark 10 parts Alisma 10 parts Poria cocos 10 parts

Red Smilax Poria Cocos 15 parts Achyranthes Knuckle 10 parts

8. The composition according to any one of the above 1-7, characterized in that the pharmaceutical composition is made into powder, tablet, block or granule, tea or capsule.

9. The medicine of the above-mentioned 8, which is a capsule.

10. The composition according to any one of 1 to 9 above is used for treating or preventing diabetes or its complications.

11. The use of the above 10, the diabetic complication is diabetic retinopathy.

Detailed ways

It will be described in detail below.

Diabetic retinopathy (hereinafter referred to as DRP) is an eye fundus disease. According to the theory of traditional Chinese medicine, the pathogenesis is as follows: Diabetic disease persists for a long time, less semen and fluid, can not support the eyes, and the eyes are not nourished; or liver and kidney Yin deficiency worsens day by day, yin deficiency and yang hyperactivity, asthenia fire burns up, burns the eyes, and causes blurred vision and even blindness. In other words, due to long-term diabetes, various parts of the body are out of balance (kidney deficiency and yin deficiency), causing the retina to lose its nourishment and even be damaged, causing a series of lesions. With the help of fundus examination, fluorescein imaging and other intuitive observation methods, modern doctors have made scientific research on this disease from the aspects of blood rheology, microcirculation, blood biochemistry, etc., and found that "blood stasis" plays an important role in its pathogenesis. Therefore, the current traditional Chinese medicine has a relatively consistent understanding of its pathogenesis: kidney deficiency is the root, yin deficiency is the root, and blood stasis is the symptom. Treatment should take both symptoms and root causes into account, and work slowly.

At present, the prescriptions and medicines that have been reported to treat this disease are all carried out on this basis. For the purpose of adjusting kidney deficiency and yin deficiency, most of them are obtained by adjusting prescriptions based on Liuwei Dihuang Decoction.

The main medicines of Liuwei Dihuang Decoction include Rehmannia glutinosa for tonifying blood, Cornus officinalis for tonifying yin, Chinese yam for tonifying qi, Alisma, Poria cocos for diuresis, Cortex Moutan for cooling blood, etc. Rehmannia glutinosa and Eclipta japonica replace the blood tonic Rehmannia glutinosa, which can strengthen the effect of nourishing the liver and kidney. In addition, if adding blood-activating and stasis-removing drugs such as salvia miltiorrhiza and Panax notoginseng to the prescription, it can nourish the liver and kidney and at the same time increase the effect of promoting blood circulation and improving eyesight. .

Thus, the present invention finds the following pharmaceutical composition for treating diabetes or its complications, which is characterized by containing yin-tonifying, qi-tonifying, blood-activating, blood-cooling, diuretic drugs and/or their extracts.

Specifically, the above-mentioned yin-tonifying medicines include Ophiopogon japonicus, Asparagus, Dendrobium, Polygonatum Polygonatum, Polygonatum, Lily, Lycium barbarum, Mulberry, Eclipta chinensis, Ligustrum lucidum, white fungus, and dogwood. Preferred are Ophiopogon japonicus, Lycium barbarum, Mulberry, Eclipta edulis, Ligustrum lucidum, and Cornus officinalis, most preferably Eclipta edulis, Ligustrum lucidum, and Cornus officinalis.

Qi-invigorating drugs include ginseng, Codonopsis pilosula, heterophylla, astragalus, Atractylodes macrocephala, yam, white lentils, licorice, etc. Preferred are ginseng, astragalus, yam, and licorice. Most preferably yam.

Drugs for promoting blood circulation include Chuanxiong, Corydalis, Turmeric, Sanleng, Salvia, Polygonum cuspidatum, peach kernel, safflower, Achyranthes bidentata, Panax notoginseng, etc. Chuanxiong, Danshen, peach kernel, safflower, Achyranthes bidentata, Sanqi are preferred, and Danshen, Sanqi and Achyranthes bidentata are most preferred.

Heat-clearing drugs include reed root, gardenia, skullcap, coptis, cork, (raw) rehmannia, scrophulariae, Moutan bark, red peony root, honeysuckle, etc. Rehmannia glutinosa, Cortex Moutan, Radix Paeoniae Rubra, Honeysuckle are preferred, Cortex Moutan is most preferred.

Diuretic drugs include Poria, Polyporus, Alisma, Akebia, Yinchen, Chixiaodou, Corn Silk, and Red Soil Poria. Poria, Alisma, red bean, corn silk, and red soil Poria are preferred, and Poria, Alisma, and red soil Poria are most preferred.

The ratio of each component in the composition of the present invention differs according to the different drugs used. For example, according to the relative weight ratio, in the composition of the present invention per unit dose, based on the raw material drug, it can contain 20 to 50 wt. parts, preferably 25 to 45 parts by weight of Yin-tonifying medicine, 10 to 30 parts by weight, preferably 10 to 20 parts by weight of Qi tonic medicine, 10 to 40 parts by weight, preferably 15 to 35 parts by weight of medicine for promoting blood circulation, 5 to 20 parts by weight, preferably 5-10 parts by weight of heat-clearing and blood-cooling medicine and 20-50 parts by weight, preferably 20-40 parts by weight of diuretic medicine. Of course, those skilled in the art can also make changes based on the present invention and according to the concept of the present invention, and various changes made on this basis also belong to the scope of the present invention.

When yin-tonifying medicines choose Eclipta chinensis, Ligustrum lucidum and Cornus officinalis, qi-tonifying medicines choose yam, blood-activating medicines choose Danshen, Sanqi, and Achyranthes bidentata, heat-clearing medicines choose Moutan Cortex, and diuretic medicines choose Poria, Alisma, and Poria cocos, An example of the preferred version of the present invention is formed as follows:

Ligustrum lucidum 15 parts Eclipta 12 parts Dogwood 12 parts

Yam 15 parts Salvia 12 parts Panax notoginseng 6 parts

Moutan bark 10 parts Alisma 10 parts Poria cocos 10 parts

Red Smilax Poria 15 parts Achyranthes bidentata 10 parts

In the present invention, the above-mentioned traditional Chinese medicine components can not only be added in the form of raw medicinal materials, but also can be extracted and added after obtaining active ingredients. The composition composed of active ingredients can not only exert the therapeutic effect of the above-mentioned prescription, but also is convenient to carry, and can reduce the dose of medicine taken by patients. In addition, by extracting active ingredients, it can help to keep the drug content stable and reduce the fluctuation of drug efficacy.

The dosage of the composition of the present invention, according to the original medicinal materials, the daily dosage is between 10g (2 qian)～100g (2 liang), the general consumption is about 20g (4 qian)～75g (1 liang), preferably 25g ( Half tael) ~ 50g (1 tael), preferably around 30g (can be ±5g or so depending on the situation).

Since the composition of the present invention contains more flavors of traditional Chinese medicines, the dose is relatively large. The daily dose of the crude drug is about 30 g, and three times a day, the dose is 8.3 to 11.7 g of the crude drug each time. The course of treatment is longer, and each course of treatment lasts up to 3 months. When choosing a dosage form, it is necessary to choose a dosage form that is small in size and easy to carry and take. Conventional decocted preparations are inconvenient to carry and take, so it is difficult to meet the above requirements. Therefore, from the perspective of long-term medication, solid preparations made from its extracts are preferred.

As solid preparations, there are capsules, tablets, granules and the like. If the present invention adopts solid preparation, according to the above-mentioned narration, extractum should be made earlier. When re-preparing granules, a certain amount of auxiliary materials can be added to promote granulation and extract dissolution. As auxiliary materials for granules, you can choose according to the common sense in this field, but you should avoid using sugars and pastes that may interfere with diabetes and are not suitable for diabetics. Fine and other accessories. When preparing compressed tablets, the specific process is such as mixing the extract into a certain amount of auxiliary materials, etc., adding softening materials, granulating, and tableting at the same time. From the point of view of formulation, the capsules can seal the extract into gelatin capsules directly or only through simple processing, and the process is simple. Simultaneously, because the capsule can release the medicinal components directly after dissolving, the medicine dissolves well, the onset of effect is large, the curative effect is stable, and it is convenient to take and small in size, so the capsule is the most preferred. Of course, on the premise of ensuring convenience and ease of administration, other oral or parenteral administration preparations such as oral liquids and liquors can also be used. Those skilled in the art can make a decision according to the composition and extraction process used specifically, and such changes all belong to the scope of the present invention.

The preparation process of the present invention is introduced below.

Because the process of extracting the extract belongs to the common knowledge well known in the art, it is not intended to be too limited in the present invention. It should be noted that the active ingredients of the medicinal materials contained in the composition may be water-soluble or fat-soluble, and some may contain both water-soluble and fat-soluble ingredients. For medicinal materials containing fat-soluble or both water-soluble and fat-soluble ingredients, the fat-soluble ingredients should be extracted by alcohol extraction or other organic solvents such as chloroform, ether, petroleum ether, etc. For medicinal materials containing water-soluble ingredients, if drug interactions are not caused, they can be mixed first and then extracted with water to simplify the process. For medicinal materials containing both water-soluble and fat-soluble ingredients, after the fat-soluble ingredients are extracted, they can also be extracted with water together with the above-mentioned water-soluble ingredients. For medicinal materials containing active ingredients of volatile oil, the loss of volatile oil during the extraction process should be avoided, or the volatile oil should be extracted first by steam distillation and other methods for later use. For medicinal materials whose active ingredients are thermally unstable, according to the conventional practice in the field of traditional Chinese medicine, they can be pulverized or the active ingredients are extracted by low-temperature methods, and then mixed into the extract.

Methods well known in the art can be used for the above extraction, for example, methods such as solvent impregnation, percolation, and reflux extraction can be used when extracting fat-soluble components. Solvents such as lower aliphatic alcohols such as methanol, ethanol, low-boiling volatile solvents such as ether, petroleum ether, vegetable oil, etc. Solvent/water mixtures such as alcohol/hydrates and the like may also be used if the solvent is fat soluble and soluble in water. When extracting water-soluble components, methods such as water immersion, decoction, ultrasonic or microwave extraction can be adopted. According to needs, medicinal acids, alkalis, etc. can also be added to the water to promote extraction or preserve active ingredients. The above methods can also be used in combination.

It should be noted that for traditional Chinese medicine, although the extract can be further purified to further reduce the amount, according to our practice, the use of ordinary water extracts and alcohol extracts with relatively low purity can be effective while ensuring the curative effect. It is economically beneficial to reduce production costs.

The following examples are given to illustrate the extraction and preparation methods.

Example 1.

The concrete composition of composition used in this example is as follows:

Ligustrum 312.5g Eclipta 250g Dogwood 250g

Yam 312.5g Salvia 250g Sanqi 125g

Moutan bark 208g Alisma 208g Poria cocos 208g

Red soil Poria cocos 312.5g Ox knee 208g

After analysis, the prescription contains fat-soluble active ingredients in Ligustrum lucidum, Cornus officinalis, Salvia miltiorrhiza and Alisma. These ingredients have low solubility in water, so these drugs are first extracted with ethanol. At the same time, these medicines also contain water-soluble active ingredients, which are extracted with water together with other medicines after alcohol extraction.

The specific sources of the above medicinal materials are as follows. Unless otherwise specified, they are identified and used according to Part One of the "Pharmacopoeia of the People's Republic of China" 2000 Edition.

Ligustrum lucidum: the ripe and dry fruit of Ligustrum lucidum Ait.

Eclipta prostrata L. dry aboveground part of Eclipta prostrata L.;

Cornus officinalis: the dried and mature pulp of Cornus officinalis Sieb.et Zucc. of Cornus officinalis;

Yam: the dry rhizome of Dioscorea opposita Thunb.

Salvia: dry roots and rhizomes of Salvia multirrhiza Bge.

Panax notoginseng; the dry root of Panax notoginseng (Burk.) F.H.Chen of Araliaceae plant;

Moutan bark: the dry root bark of Paeonia suffruticosa Andr.;

Alisma: the dry tuber of Alisma orientalis (Sam.) Juzep.

Poria cocos: the dried sclerotia of Polyporaceae fungus Poria cocos (Schw.) Wolf;

Poria cocos: the dried rhizome of Smilax china L., a plant of Liliaceae (according to the local traditional Chinese medicine standard of Hunan Province);

Achyranthes: the dry root of Achyranthes bidentata Bl.

2. Operation steps

The above eleven flavors and Panax notoginseng are crushed into fine powder, and set aside; Moutan cortex is steam distilled, and about 500ml of the distillate is collected, and 40g of β-cyclodextrin is added, stirred at 40°C for 1.5 hours to make inclusions, refrigerated for 24 hours, and pumped Filter and dry the clathrate below 60°C for later use; the dregs and liquid medicine are stored separately. Take Ligustrum lucidum, Cornus officinalis, Salvia miltiorrhiza, and Alisma and add 90% ethanol to heat and reflux to extract twice, each time for 2 hours, combine the extracts, filter, and concentrate the filtrate under reduced pressure to a relative density of 1.30-1.40 (60-70°C heat Add 50 g of Panax notoginseng fine powder, mix well, dry at 60-70° C., and pulverize into coarse powder. Reserve; the rest of the five flavors such as Eclipta chinensis are added to the above-mentioned alcohol-extracted medicinal residues and moutan cortex distilled, and the medicinal residues are decocted twice, each time for 2 hours, combined with the decoction liquid, filtered, and the filtrate is concentrated to a relative density of 1.30 -1.40 (60-70°C heat test) thick paste, add the remaining notoginseng fine powder above, mix well, dry under reduced pressure at 60-70°C, and crush into coarse powder. Add the above-mentioned alcohol extract extract powder and β-cyclodextrin inclusion compound, mix thoroughly, fill capsules according to the conventional method, and make about 1000 capsules, and the product is ready. Each capsule weighs about 0.5g, which is equivalent to containing about 2.7g of crude drug.

Embodiment 2-4

According to the above operation, the magnification is about 12 times, repeated 3 times, and the results are shown in Table 1 below.

Table 1

Example number Example 2 Example 3 Example 4 Dosage (Kg) 31.75 31.75 31.75 Weight of alcohol extraction extract (g) 1350 1250 1250 After alcohol extraction, add Panax notoginseng powder (%) 40% 40% 40% Weight of water-extracted dry extract (g) 4750 4450 4400 Add Panax notoginseng powder after water extraction (%) 60% 60% 60% β-cyclodextrin inclusion complex weight (g) 350 330 320 Dry powder weight after mixing (g) 6400 5970 5840 Capsule quantity (tablets) 12700 11800 11500

The above-mentioned three batches of products were determined according to conventional methods for the content determination of specific components, and the results are shown in Table 2 below.

Table 2

Example number Example 2 Example 3 Example 4 Moisture (%) 4.52 3.89 3.75 Tanshinone II _A content (%) 0.057 0.060 0.061 Oleanolic acid content (%) 0.59 0.61 0.62 Ursolic acid content (%) 0.37 0.39 0.39

It shows that the product obtained by adopting the composition and preparation method of the present invention has stable active ingredient content and is suitable for industrial production.

The effect of the present invention is further illustrated by the pharmacological experiment data below.

Pharmacological Experiment Example 1 Toxicological Experiment

(1) Acute toxicity test:

20 Balb/c mice, weighing 18-22 grams, of both sexes, fasted for 16 hours before the test. Get the capsule of Example 1, after peeling off the capsule shell, use distilled water to make 2.0 grams (according to the raw material drug, the same below)/milliliter concentration solution to mice, 0.8 milliliters/20 grams, intragastric administration 3 times in 24 hours . Observe the changes in animal behavior and animal death within 7 days after administration, and calculate LD ₅₀ .

The animal had no obvious abnormality and no death within 7 days, and the LD ₅₀ could not be calculated. The tolerance of the composition of the present invention is >240g/kg, indicating that the composition of the present invention is relatively safe.

(2) Long-term toxicity test:

SD clean rats, half male and half male, 7-9 weeks old, weighing 65-75 grams. Experiments were carried out after one week of acclimatization.

Rats were randomly divided into three groups—a high-dose group, a low-dose group, and a negative control group, with 30 rats in each group, half male and half male. Administration Each group is given the aqueous solution of the composition obtained in Example 2 (dissolved in water after peeling off the capsule shell) every day, and the dosage is 30g/kg for the high-dose group and 15g/kg for the small-dose group. For intragastric administration, the control group was 1.5ml/100g, and the administration concentrations of the administration groups were 2.0g/ml and 1.0g/ml respectively.

The laboratory maintains a 12-hour light-dark rhythm, with a temperature of 25±2°C and a relative humidity of about 55%. 6 consecutive months.

Through animal clinical observation, hematology, biochemistry, and histopathological examination, no obvious toxic and side effects were found in the animals, and the results indicated that the dose below 30g/kg per day for clinical application is relatively safe.

As can be seen from the above toxicological test results, the composition of the present invention is actually non-toxic. Diabetics can take it for a long time.

Pharmacological Experimental Example 2. The effect of the composition of the present invention on diabetic model rabbits.

The diabetic retinopathy (Diabetic Retinopathy, DRP) that the present invention aims at does not have ready-made and perfect animal model. According to existing theories, the etiology and pathogenesis of the disease are mainly caused by diabetes (or hyperglycemia), and the main pathophysiology is: three high factors, namely high capillary permeability, high blood viscosity, and high platelet activity. For this reason, the present inventors established an animal model by using alloxan to cause hyperglycemia in rabbits and maintain it for 90 days.

1. Apply this product to treat diabetic rabbits, observe blood sugar, clinical manifestations, retinal general pathology and ultrastructure, cAMP (cyclic adenosine monophosphate), 6-keto-PGF _1a (prostaglandin F), TXB in local retinal tissues ₂ (thromboxane), SOD (superoxide dismutase), red blood cell flexibility, blood platelet adhesion reaction, platelet membrane granule protein in plasma, euglobulin dissolution time, etc.

Experimental Materials

Drugs and reagents:

1) Composition of the present invention (hereinafter referred to as JM sometimes), the extract preparation of the composition of above-mentioned embodiment 1, peel off capsule shell just before use, be made into required concentration with distilled water, and the dosage for animals is represented by the original medicine amount.

2) SOD radioimmunoassay kit: provided by Nanjing Jindun Pharmaceutical Factory, batch number: 971205.

3) cAMP radioimmunoassay kit: Provided by the Thrombosis Laboratory of Suzhou Medical College, batch number, 971120.

4) Plasma TXB ₂ kit: Provided by the Thrombosis Laboratory of Suzhou Medical College,

5) 6-keto-PGF _1a kit: Same as above

6) α-granule membrane protein 140 (GMP-140) radioimmunoassay kit: same as above.

All other reagents and equipment are commercially available.

animal

Healthy big-eared white rabbits, weighing 1.2-1.5kg, male and female.

main instrument

SCOT portable blood glucose measuring instrument, FJ-2008PV-immunity counter (state-owned No. 262 Factory), 2332 spectrophotometer (Shanghai Third Analytical Instrument Factory), ELT viscometer (Chengdu Instrument Factory), WPT-III platelet adhesion meter (Jiangsu Wuxi Shitangwan Medical Electronic Instrument Factory), etc.

Experimental methods and results

(1) Experimental method

1. Modeling method

Adopt the following method: get healthy big-eared white rabbits, after fasting for 12 hours, ear vein blood collection measures blood sugar value with GLUCO SCOT portable blood glucose measuring instrument, selects the animal intravenous injection alloxan (from Sigma company) that blood sugar value is below 10mg/ml ) 200mg/ml, blood was collected after 48 hours to measure fasting blood glucose, those whose blood glucose was above 200mg/kg were taken as experimental animals, and the control group was injected with normal saline in the same way. For fasting blood glucose, animals with fasting blood glucose values greater than 20 mg/ml were injected with alloxan once in the same way to maintain hyperglycemia. At the same time, fasting blood glucose was monitored after injection, and fasting blood glucose was measured on the 61st day. Animals greater than 20 mg/ml were selected for the next grouping and administration experiment.

2. Animal grouping and drug administration method

The big-eared white rabbits that had been modeled for 60 days were randomly divided into the following 5 groups, with 12 rabbits in each group, and 8 normal rabbits raised during the same period, whose fasting blood glucose was below 10mg/ml, were used as the control group.

Control group (normal control group): fed with distilled water 8ml/kg on an empty stomach every day.

Model group (model group control group): fed with distilled water 8ml/kg on an empty stomach every day.

JM high group (the high-dose group of the composition of the present invention, the same below): the concentration is 0.36g/ml, and the dosage is 8ml/kg.

JM middle group: 0.18g/ml, 8ml/kg.

JM group: 0.09g/ml, 8ml/kg.

3. Specimen collection and processing

1) Blood sample collection

After fasting for 12 hours, blood was collected from the heart before anesthesia to measure platelet adhesion reaction, euglobulin lysis time, red blood cell flexibility, and plasma α-granule membrane protein 140 (GMP-140).

2) Electron microscope specimens and routine pathological examination of retinal tissue of the right eye

After the rabbits in each group that had been administered for 30 days were anesthetized with pentobarbital, the right eye of the animal was drawn out from the anterior chamber, and then about 1ml of 2.5% glutaraldehyde solution was injected for perfusion fixation, and the eyeball was quickly taken out and gently Cut the cornea, peel off the lens and vitreous body, cut the outer half of the cup-shaped retinal tissue and place it in 2.5% glutaraldehyde for electron microscope examination, and fix the other half with 10% formalin for general pathological examination . Place the retinal tissue block in 2.5% glutaraldehyde fixative solution (4°C) overnight, cut out the small blood vessels with thick surface under the dissecting microscope, post-fix with 1% OsO ₄ , dehydrate with gradient acetone, soak and embed in EPON812 , LKBIII ultrathin microtome section, uranyl acetate-lead citrate staining, Hitachi H-600 transmission electron microscope observation. The other half of the retinal tissue was routinely sectioned, stained with HE, and observed with a light microscope.

3) Preparation of left eye retinal homogenate specimen

At the same time, the left eyeball was taken out, the retina was peeled off on the ice cutting according to the above method, the blood on the surface was sucked out with filter paper, after weighing, 5% homogenate was made by adding ice saline and using a homogenizer, and the homogenate was processed at 4000 rpm After centrifugation at low temperature for 25 minutes, the supernatant was taken and stored in a -20°C refrigerator for measuring SOD activity, TXB ₂ , 6-keto-PGF _1a , and cAMP.

4) Observation indicators and detection methods

①Blood glucose measurement: Use a portable GLUCO SCOT instrument to measure blood glucose, and take blood from the edge of the ear to measure blood glucose.

②SOD determination: SOD radioimmunoassay kit (from Nanjing Jindun Pharmaceutical Factory) was used for determination. Tissue and serum processing and determination were performed according to the instructions.

③Cyclic AMP (cAMP) in retinal tissue: the radioimmunoassay kit provided by the Thrombus Research Office of Suzhou Medical College, and the tissue homogenate supernatant was used for the detection of this index.

④Determination method of TXB ₂ and 6-Keto-PGF _1a in retinal tissue: the retinal tissue fluid was treated as before, and the detection method was carried out according to the instructions of the radioimmunoassay kit.

⑥ Detection of red blood cell flexibility: use a microporous filter for detection, specific method: anticoagulate the collected blood sample with sodium citrate, take about 1ml of anticoagulated blood, measure the hematocrit, and dilute it with normal saline for 5 (add 4ml of normal saline), put the diluted blood into a 10ml syringe, then filter through a microporous filter (cellulose acetate filter membrane, pore size: 5μm), centrifuge, measure the hematocrit in the filtrate, and calculate the filtration percentage.

⑥Determination of platelet adhesion

2.7ml of blood was taken from the heart, placed in a siliconized test tube containing 0.3ml of 3.13% sodium citrate solution, and mixed gently. Then take 1.5ml of anticoagulant blood and add it into a spherical glass bottle with a capacity of 12ml, fix the spherical bottle on the rotating device of the platelet adhesion instrument, and rotate it at a speed of 3 revolutions per minute for 15 minutes to make the blood fully contact with the bottle wall. After rotating, take 1ml of blood from the ring bottle (after adhesion) and the test tube (before adhesion) respectively, and add it to a large test tube containing 19ml of 3.13% sodium citrate solution, cover the mouth of the test tube with a plastic film, repeat Pour 3 times to make it even, let it stand at room temperature for 2 hours, take the upper layer of the test tube for platelet count. Each tested sample was measured in duplicate, and the mean value was taken to calculate the platelet adhesion rate.

⑦Determination of plasma euglobulin lysis time (ELT)

Take blood from the heart, separate the plasma according to the above method, take 0.5ml of fresh plasma, add it to a conical centrifuge tube containing 9ml of acetic acid solution after cooling, mix well and put it in the refrigerator at 4°C for 30 minutes, the euglobulin is flocculent The precipitate was separated out and centrifuged (3000 rpm) for 5 minutes. Gently pour off the supernatant, keep the precipitated part, invert the centrifuge tube on the filter paper for about 2 minutes, absorb the remaining acid solution, then place the centrifuge tube in a glass constant temperature water bath at 37±0.1°C, add 0.5ml pH9.0 Boric acid solution, carefully stirred with a thin glass rod to dissolve the precipitate, then add 0.025mol/L calcium chloride solution and mix well, about 1-2 minutes, the liquid in the tube begins to solidify. Record the time from the formation of the clot to the complete dissolution of the clot, the time required for this process is the ELT, and then divide 10000 by the ELT, which is the unit of lytic activity.

⑧Clinical observation: 60 days after modeling, grouping and administration began. Because the blood sugar level of the animals remained high, the normal physiological functions in the body were affected, and the animals showed certain clinical symptoms and signs. We made statistics on the body weight and mortality.

4) Statistical processing: due to the use of alloxan to make models, the mortality rate of animals is relatively high, and there are many detection indicators. Between-group t-test.

Experimental results

1. Effect on blood sugar

The results can be seen from Table 3, the blood glucose of the model animals was significantly higher than that of the normal control group. After being treated with the composition JM of the present invention, the blood sugar level decreased to a certain extent. Compared with the model control group, the blood sugar level of each administration group decreased significantly on the 15th day after administration, and the reduction was more obvious on the 30th day, reducing the difference It is statistically significant.

Table 3 Effects on Blood Sugar of Diabetic Rabbits (X±SD)

group Number of cases n Blood glucose level (mg/ml) Before modeling before administration 15 days after administration Reduce the difference 30 days after administration Reduce the difference normal control 8 7.5±1.3 7.6±10** 7.1±0.9 0.4±10 7.4±12 0.2±11 Model 6 7.6±1.4 67.9±6.7 55.7±8.1 12.1±4.5 39.9±7.7 28.0±1.9 JM Gao 9 7.7±0.9 68.2±6.8 38.3±4.8 29.8±7.6** 23.4±5.4 44.8±9.0** in JM 8 7.9±1.3 65.3±7.5 42.8±7.6 22.5±11.4* 25.7±6.5 39.6±8.2** JM small 6 8.1±1.4 66.8±6.6 44.3±5.9 22.5±3.6** 28.9±6.2 37.9±7.5*

Compared with the model group, *, P<0.05, **: P<0.01;

2. Clinical observation

1), the impact on the clinical manifestations of diabetic animals

Compared with the normal control animals, the animals in the model group showed increased food intake, decreased body weight, and increased drinking water, which were similar to human clinical diabetes with polydipsia, hunger, and emaciation. The signs and symptoms of the treatment group were mild. The changes in body weight were counted. It can be seen from Table 4 that the average body weight of the hyperglycemia animal model not only did not increase, but decreased, which was significantly lower than that of the normal control group. slowing down, in which the JM high-dose and medium-dose groups gained weight by 9.7% and 7.6% respectively.

Table 4 Effect on Body Weight (X±SD)

Group Number of cases Before administration 30 days after administration % Weight Gain normal control 8 1.91±0.27 2.59±0.30** 35.8±8.9** Model 6 1.46±0.33 1.30±0.27 -10.6±5.6 JM Gao 9 1.41±0.31 1.56±0.28 9.7±10.3** in JM 8 1.37±0.29 1.48±0.34 7.6±3.0** JM small 6 1.36±0.39 1.30±0.31 -3.7±5.1

Compared with the model group, **: P<0.01.

2), the impact on the mortality rate of diabetic rabbits

In the long-term hyperglycemia state, rabbits have a relatively high mortality rate, and the mortality rate of each group is about 50% during the 60-day modeling period. Animals that die after 1 week of administration are included in the statistics that may have an impact on the drug. For detailed statistics, see Table 5, each administration group of JM has a tendency to reduce animal death.

Table 5 Diabetic rabbit model and animal death during administration

group Number of animals before modeling Mortality rate within 1 week from modeling to administration (%) Total number of cases 1 week after administration (n) Number of deaths after 1 week of administration The number of animals that completed the dosing cycle Mortality % after 1 week of administration normal control 8 0 8 0 8 0 Model 25 48 12 6 6 50 JM high twenty three 52.2 12 3 9 25 in JM twenty four 50 12 4 8 33.3 JM Small twenty three 52.2 12 6 6 50

3. Effects on retinal vascular histopathology

Routine pathological and electron microscopic examinations of retinal tissue were performed on the animals that completed the administration cycle. There was no obvious abnormality in each group by visual inspection.

Under the light microscope, a small number of animals showed obvious edema, arteriolar lumen narrowing, small veins were thick and distorted, local small veins were tortuous and dilated, and capillaries were obviously distorted. Under the electron microscope, basal small vessel lumen narrowing, endothelial cytoplasm thinning, segmental dissolution and rupture, edema under the basement membrane, exposed collagen fibers, dense spots and dense bodies of smooth muscle cells were common in the preparation group. , Myofilaments are still clearly visible, and there are different degrees of swelling of mitochondria in endothelial cells, vacuolation and expansion of endoplasmic reticulum. Mitochondria in pericytes were significantly degenerated, and endothelial cells had cytoplasmic protrusions centered on the nucleus to the lumen, aggravating lumen stenosis, and capillary basement membrane thickening. Increased fat particles were seen in the retinal pigment epithelium. The model control group showed more obvious and serious symptoms, and the number of lesions is shown in Table 6.

The pathological results showed that some pathological changes appeared in the retinal vascular tissue of the diabetic model group, and pathological changes were seen in only a few animals by light microscopy. Under the electron microscope, the changes of mitochondria, endoplasmic reticulum and cytoplasmic lysis of vascular endothelial cells can be seen in most of the model animals. The number of animals in the drug treatment group is less than that of the model control group, and the number of cases in the JM high-dose group is less. In order to objectively evaluate the differences between the groups, the results of light microscopy and electron microscopy were combined and compared using the pathological integral method. Since the changes seen by light microscopy were serious changes, the weight of light microscopy was increased, and the abnormalities detected by light microscopy in each group were compared. Animals were scored as 2, animals with normal light microscopy were scored as 0, animals with pathological changes in the results of electron microscopy were scored as 1, and normal animals were scored as 0. The pathological points of the cases were compared with the average points of each group, and the measurement data was processed. The results are shown in Table 6. Compared with the model group, the JM high group can significantly reduce the pathological points (P<0.05), suggesting that JM has a better effect on preventing and treating rabbits. The role of diabetic retinopathy.

Table 6 Pathological examination results of rabbit retina (X±SD)

group The total number of cases that completed the dosing cycle (n) Dose/kg The number of abnormal animals under light microscopy The number of cases of abnormal blood vessel cells detected by electron microscope mean lesion score normal control 8 8.0ml 0 0 0 Model 6 8.0ml 3(50.0) 6(100) 2.00±1.09 JM High 9 3.0g 1(11.1) 3 (33.3) 0.56±1.01* in JM 8 1.5g 2(25.0) 4(50.0) 1.00±1.31 JM Small 6 0.8g 2(33.3) 6(100) 1.67±1.03

Compared with the model group, *: P<0.05 (percentage in brackets).

4. Effects on retinal tissue SOD

It can be seen from Table 7 that the SOD activity of the retinal tissue of the rabbits in the long-term hyperglycemia state was significantly lower than that of the normal control group, and after drug treatment, the JM high-dose and medium-dose groups could significantly increase the SOD activity of the retinal tissue of diabetic animals.

The influence of table 7 on retinal tissue SOD (X±SD)

group Number of cases (n) Dose/kg SOD(U/100mg pro) normal control 8 8.0ml 2.3±0.9 Model 6 8.0ml 0.7±0.6 JM Gao 9 3.0g   1.5±0.6* in JH 8 1.5g 1.6±0.7* JM small 6 0.8g 1.0±1.2

Compared with the model group, *P<0.05.

5. Effects on the content of cAMP in the retinal tissue of diabetic rabbits

It can be seen from Table 8 that compared with normal animals, cAMP in the retinal tissue of diabetic model animals decreased significantly, and the difference was statistically significant (p<0.01). After treatment in the JM high group, cAMP increased significantly, compared with the model group, the difference was statistically significant (P<0.05).

Table 8 Effects on cAMP content in retinal tissues of diabetic rabbits (X±SD)

Group Number of animals (n) Dose/kg cAMP content (pm/ml) normal control 8 8.0ml 37.5±5.8** Model 6 8.0ml 27.9±4.6 JM Gao 9 3.0g 36.5±4.2** in JM 8 1.5g 31.2±4.9 JM small 6 0.8g 29.9±6.6

Compared with the model group, **: P<0.01;

6. Effects on retinal TXB ₂ and 6-Keto-PGF _1a in diabetic animals

Table 9 Retina tissue of diabetic animals

Effect of TXB ₂ , 6-Keto-GF _1a (X±SD)

group Number of animals (n) Dose/kg TXB2(pg/ml) 6-K-PGF1a(pg/ml) normal control 8 8.0ml  17.7±3.5** 22.2±3.1 Model 6 8.0ml 26.3±4.2 13.2±5.1 JM Gao 9 3.0g 22.3±4.0 17.3±4.1 in JM 8 1.5g 24.5±5.9 15.7±4.0 JM small 6 0.8g 24.9±6.3 15.3±5.8

It can be seen from Table 9 that the TXB ₂ in the retinal tissue of the diabetic model animals increased significantly, and the 6-Keto-PGF _1a decreased significantly. After treatment with JM, the TXB ₂ of the animals tended to decrease, and the 6-Keto-PGF _1a increased to a certain extent .

7. Effect on α-granule membrane protein 140 (GMP-140) in plasma of diabetic animals

Table 10 to 140 of α-granule membrane egg in plasma

(GMP-140) Effect (X±SD)

Group Number of animals (n) Dose/kg GMP-140(ng/ml) normal control 8 8.0ml 5.6±3.1** Model 6 8.0ml 19.4±5.2 JM Gao 9 3.0g 14.2±4.2* in JM 8 1.5g 17.5±6.7 JM small 6 0.8g 17.9±6.5

Compared with the model group, *, P<0.05, **: P<0.01.

α-granule membrane protein 140 is an index of platelet activation degree in vivo. It can be seen from Table 10 that the α-granule membrane protein 140 of diabetic animals is significantly increased. After JM treatment, the α-granule membrane protein 140 in plasma of diabetic animals has decreased effect or trend.

8. Effect on the flexibility of red blood cells

The flexibility of erythrocytes was detected by the micropore filtration method, expressed as a filtration percentage, the rate of erythrocytes passing through the micropores of diabetic animals decreased significantly, and its flexibility decreased. Plasticity and flexibility, the results are shown in Table 11.

The impact of table 11JM on the erythrocyte microfiltration rate of diabetic rabbits (X±SD)

group Number of animals (n) Dose/kg   Red blood cell filtration rate % normal control 8 8.0ml 65.6±11.5 Model 6 8.0ml 31.4±9.8 JM Gao 9 3.0g 45.2±11.0 in JM 8 1.5g 43.4±12.5 JM small 6 0.8g 37.9±11.3

9. Effect of JM on platelet adhesion reaction in diabetic rabbits

Compared with the normal control group, the platelet adhesion rate of the model group was significantly increased, and each JM group had a tendency to reduce the platelet adhesion rate of diabetic animals.

The influence of table 12JM on platelet adhesion rate (X ± SD)

group Number of animals (n) Dose/kg   Platelet adhesion rate % normal control 8 8.0ml 26.4±4.9 Model 6 8.0ml 36.7±7.8 JM Gao 9 3.0g 32.5±5.8 in JM 8 1.5g 32.6±6.4 JM small 6 0.8g 35.1±5.6

10. The effect of JM on the dissolution time of blood euglobulin in diabetic rabbits

It can be seen from Table 13 that, compared with the normal control group, the fibrinolytic activity units of the animals in the model group were significantly reduced, indicating that diabetes causes a decline in the body's fibrinolytic activity, and JM has a certain increase in the fibrinolytic activity units.

The impact of table 13JM on the fibrinolytic activity of diabetic animals (X±SD)

group Number of animals (n) Dose/kg Plasminolytic activity unit u normal control 8 8.0ml 65.4±7.5 Model 6 8.0ml 47.8±11.2 JM Gao 9 3.0g 51.5±8.9 in JM 8 1.5g 51.06±9.7 JM small 6 0.8g 49.6±10.7

Visible by above-mentioned data, after treating with JM, above-mentioned each index all has slowing effect or trend in various degrees, and the result shows that JM all has improving effect to the main pathophysiological index of three aspects of this disease, prompts composition of the present invention to this disease. The disease has a better therapeutic effect.

Pharmacological Experimental Example 3. Effects of Compositions of the Present Invention on Blood Glucose and Hemorheology in Diabetic Model Rats

experimental method

1. Modeling method

Select adult pure-line male Wistar rats with a body weight of 210-250 grams to measure fasting blood glucose and remove animals with abnormal blood sugar. After 6 hours of fasting, each mouse is intraperitoneally injected with streptozotocin (from Sigma Company, with 0.1mmol/L citrate buffer solution (pH4.5)) 65mg/kg to induce diabetes, and three days later, the rat tail blood was collected to measure the fasting blood glucose, and those with blood glucose greater than 40mg/ml and persistent positive urine sugar were regarded as experimental diabetic animals. They were randomly divided into 5 groups, 10 rats in each group, and 10 rats were set up as a normal control group, and the blood glucose before and after administration of each group was measured at the same time.

Each group was intragastrically administered daily after grouping. The dosage is shown in Table 14. After two consecutive weeks, blood was collected from the eyeballs for the following hemorheology indicators:

①Whole blood viscosity: Adopt the Japanese ELD type cone-plate variable-speed rotary viscometer, take the cutting speed as 1.92S ^-1 , and automatically print the records.

②Plasma specific viscosity: The capillary viscometer of Shanghai Medical University was used to calculate the ratio of the time required for plasma to pass through the capillary and the time required for the same volume of normal saline to pass through the capillary.

③ Erythrocyte sedimentation rate: Use a hematocrit tube with an inner diameter of 2.8 mm and a length of 100 mm to observe the erythrocyte sedimentation rate after 1 hour

④ Hematocrit: Use the hematocrit tube after recording the erythrocyte sedimentation rate to continue the experiment, centrifuge at 3000 rpm for 30 minutes, and calculate the hematocrit.

⑤ Plasma fibrinogen: salting out biuret method.

Experimental results

It can be seen from Table 14 that the blood sugar of diabetic rats is significantly higher than that of normal rats, and each administration group of JM has a lowering effect or trend in different degrees compared with the model group.

The impact of table 14JM on the blood sugar of diabetic rats (X ± SD)

group Number of cases Dose (/kg)                                                              Before modeling when administering 15 days after administration reduce the difference normal control 10 10ml 9.5±1.0 9.4±1.2** 9.6±1.5** -0.2±1.1** Model 10 10ml 9.4±1.2 46.7±7.4 36.5±8.1 10.3±5.4 JM Gao 10 5.6g 8.9±1.6 45.3±7.2 22.7±4.5** 22.6±5.4** in JM 10 2.8g 8.8±1.5 42.7±7.8 31.0±7.2 11.6±8.1 JM small 10 1.4g 9.6±1.7 44.3±6.2 31.6±6.2 12.7±9.0

**: P<0.01

Table 15 influences (X ± SD) on the hemorheology of diabetic rats

group Whole blood specific viscosity ratio)1/sec (Plasma specific viscosity (ratio) Hematocrit(%) Erythrocyte sedimentation rate (mm/h) Fibrin (g/L) normal control 27.8±7.2** 1.6±0.1 48.6±6.7** 1.2±0.9** 2.3±0.4 Model 62.4±11.5 1.8±0.1 67.8±5.9 2.2±0.5 1.6±0.5 JM Gao 45.5±6.7** 1.7±0.1 56.0±6.9** 1.6±0.5** 1.9±0.8 in JM 49.7±11.8* 1.8±0.2 57.7±7.6** 1.6±0.8 2.0±0.7 JM small 45.8±12.3** 1.7±0.1 60.3±6.4 1.8±1.2 1.9±0.9

Compared with the model group, *: P<0.05, **: P<0.01.

It can be seen from Table 15 that the hemorrheology indexes of the diabetic model rats were significantly changed compared with the normal control group, showing that the blood viscosity, hematocrit, and erythrocyte sedimentation rate all decreased, and the fibrinogen content increased. The changes of the indicators in each JM administration group were significantly slowed down or had a slowing down trend.

The changes in blood sugar and hemorheology in diabetic rats induced by streptozotocin were detected. The model animals showed a significant increase in blood sugar, and the hemorheology showed blood viscosity, plasma viscosity, and red blood cell pressure. Volume and erythrocyte sedimentation rate decreased, and fibrinogen content increased. Each administration group of JM has a certain hypoglycemic effect, and has a slowing effect or trend on the changes of the above-mentioned hemorheology indexes. The results suggest that JM has a certain therapeutic effect on DRP.

Claims (8)

1. be used for the treatment of or the pharmaceutical composition of prevent diabetes or its complication, it is characterized in that containing nourishing YIN, QI invigorating, invigorate blood circulation, clearing away heat and cooling blood, diuretic medicine and/or their extract,

Wherein, described nourishing YIN medicine is Herba Ecliptae, Fructus Ligustri Lucidi and Fructus Corni;

The QI invigorating medicine is a Rhizoma Dioscoreae;

Blood circulation promoting medicine is Radix Salviae Miltiorrhizae, Radix Achyranthis Bidentatae and Radix Notoginseng;

The heat clearing away medicine is a Cortex Moutan;

The diuretic medicine is Poria, Rhizoma Alismatis and Rhizoma et Radix smilacis ocreatae;

And, in crude drug, contain 20～50 weight portion YIN-tonifying drug, 10～30 weight portion Qi-tonifying drugs, 10～40 weight portion blood circulation promoting medicines, 5～20 weight portion heat removing and blood cooling medicine and 20～50 weight portion diuretic medicines.

2. according to the compositions of claim 1, wherein the complication of diabetes is diabetic renal papillary necrosis.

3. according to the compositions of claim 1 or 2, it is characterized in that, contain 25～45 weight portion YIN-tonifying drug, 10～20 weight portion Qi-tonifying drugs, 15～35 weight portion blood circulation promoting medicines, 5～10 weight portion heat removing and blood cooling medicine and 20～40 weight portion diuretic medicines in crude drug.

4. according to the compositions of claim 1 or 2, wherein each composition in the weight proportion of raw material is:

12 parts of 12 parts of Fructus Corni of 15 portions of Herba Ecliptaes of Fructus Ligustri Lucidi

6 parts of 12 portions of Radix Notoginseng of 15 parts of Radix Salviae Miltiorrhizaes of Rhizoma Dioscoreae

10 parts in 10 parts of Poria of 10 portions of Rhizoma Alismatis of Cortex Moutan

10 parts of 15 parts of Radix Achyranthis Bidentataes of Rhizoma et Radix smilacis ocreatae

5. according to the compositions of claim 1 or 2, it is characterized in that the dosage form of this pharmaceutical composition is tablet, piece agent or granule, medicinal tea or capsule.

6. according to the pharmaceutical composition of claim 5, be capsule.

7. each the purposes of compositions in the medicine of preparation treatment or prevent diabetes or its complication of claim 1～6.

8. according to the purposes of claim 7, diabetic complication is a diabetic renal papillary necrosis.