Pharmaceutical composition for improving diabetic nephropathy and preparation method and application thereof

Abstract

The invention discloses a pharmaceutical composition for improving diabetic nephropathy as well as a preparation method and application of the pharmaceutical composition. The pharmaceutical composition is prepared from the following raw materials in parts by weight: 10 to 20 parts of folium ginkgo, 10 to 20 parts of fructus corni, 8 to 15 parts of rhizoma dioscoreae, 6 to 10 parts of radix rehmanniae praeparata, 5 to 8 parts of radix astragali seu hedysari and 5 to 8 parts of poria cocos. Animal experiments prove that the pharmaceutical composition disclosed by the invention can obviously increase the level of serum IL-10, obviously reduce the levels of serum MCP-1, IL-12, BUN and Scr, effectively improve the three-more and one-less symptoms of DN mice and relieve pathological changes, can better prevent and treat diabetic nephropathy, and has a wide clinical application prospect.

Description

Technical Field

[0001] The present invention belongs to the technical field of Chinese medicine compositions, and in particular relates to a medicine composition made from Chinese medicinal materials as raw materials, and a preparation method and application thereof. Background Art

[0002] Currently, diabetes is a serious health problem worldwide. According to the International Diabetes Federation (IDF), by 2023, the number of adults with diabetes worldwide will be about 465 million, and the number of people with diabetes in my country will be about 160 million. Among the chronic complications of diabetes, diabetic nephropathy (DN) is a common and most difficult to treat microvascular complication, with an incidence of about 30%-40% of diabetic patients. The main clinical manifestations are varying degrees of proteinuria and renal impairment. The causative factors may include high blood sugar, high blood pressure, high blood lipids, genetic factors, smoking, overweight and obesity, and unreasonable diet.

[0003] Traditionally, DN is considered an endocrine metabolic disease, but modern research suggests that DN is also a chronic inflammatory disease. The metabolic inflammatory response is often accompanied by the infiltration and activation of monocytes and macrophages, and the inflammatory factors produced can further cause damage to renal intrinsic cells, promoting the occurrence and development of DN. Studies have shown that DN is closely related to inflammatory response and macrophage polarization, among which abnormal glucose metabolism is one of its inflammatory pathogenesis; persistent hyperglycemia can lead to the formation of advanced glycation end products (AGEs), which are key substances in the occurrence and development of DN. Macrophages are closely related to high blood sugar levels, glomerular immune complex deposition, progressive fibrosis, and increased chemokines in DM model animals: On the one hand, M1 macrophages can promote inflammatory responses by secreting proinflammatory factors such as interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS), causing damage to renal intrinsic cells; on the other hand, M2 macrophages can inhibit inflammatory responses by secreting a large amount of anti-inflammatory factors such as IL-10 and arginase-1 (Arg-1), thereby promoting the repair and reconstruction of damaged tissues. Therefore, regulating macrophage polarization and inhibiting inflammatory responses are one of the important strategies to delay the progression of DN.

[0004] At present, the main Western medicines used in the clinical treatment of DN are: angiotensin converting enzyme inhibitors (ACEI), angiotensin II receptor antagonists (ARB), sodium-glucose cotransporter 2 (SGLT2) inhibitors, metformin, etc., which are expensive, and adverse reactions have been reported in clinical applications. Traditional Chinese medicine has a long history and significant efficacy in the treatment of DN. Common Chinese medicine compound prescriptions such as Liuwei Dihuang Pills, Jinkui Shenqi Pills, Shenqi Dihuang Decoction, etc., have relatively few studies on their application and inhibition of inflammation. The present invention provides a pharmaceutical composition that can effectively inhibit inflammation and improve diabetic nephropathy, as well as its preparation method and application. At present, there are no relevant reports on the use of this combination to improve or treat diabetic nephropathy. Summary of the invention

[0005] The purpose of the present invention is to provide a pharmaceutical composition for improving diabetic nephropathy with significant efficacy and controllable quality, as well as a preparation method and application thereof.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions: A pharmaceutical composition for improving diabetic nephropathy, characterized in that it comprises the following raw materials in weight components: 10-20 parts of ginkgo leaves, 10-20 parts of cornus officinalis, 8-15 parts of yam, 6-10 parts of rehmannia root, 5-8 parts of astragalus, and 5-8 parts of poria.

[0007] Preferably, the weight ratio of the ginkgo leaves to the cornus officinalis is 1:1, and the drug has the best effect in this ratio.

[0008] Preferably, the raw materials include the following components by weight: 10 parts of ginkgo leaves, 10 parts of cornus officinalis, 8 parts of yam, 6 parts of rehmannia root, 5 parts of astragalus, and 5 parts of poria.

[0009] The second object of the present invention is to provide a method for preparing the above-mentioned pharmaceutical composition, comprising the following steps: (1) Ginkgo biloba leaves, Cornus officinalis, Rehmannia root and Astragalus membranaceus are extracted by reflux with ethanol, and the ethanol extract is recovered by vacuum decompression until there is no alcohol taste, and concentrated to obtain an ethanol extract concentrate and medicinal residues for later use; (2) The above-mentioned drug residues, yam and poria are boiled in water, the decoction is filtered, the filtrate is concentrated, centrifuged, the supernatant is collected, and after further concentration, it is combined with the alcohol extract concentrate of step (1), concentrated, and dried to obtain an extract powder, thereby obtaining a pharmaceutical composition.

[0010] Preferably, the weight of ethanol added in step (1) is 8-16 times the weight of the medicinal materials, that is, the weight of ethanol added is 8-12 times the weight of ginkgo leaves, cornus officinalis, rehmannia root, and astragalus, and the concentration is 30-80%. The extraction is performed by reflux for 2-3 times, each time for 1.0-1.5 hours.

[0011] Preferably, the amount of water added in step (2) is 8-16 times the weight of the medicinal materials, that is, the weight of the water added is 10-16 times the weight of yam and poria, and the decoction is divided into two times, each time for 1.0-1.5 hours, the decoctions are combined, and the decoctions are concentrated to an amount equivalent to 0.8g / ml-1.2g / ml of the raw medicinal materials, centrifuged, and the supernatant is combined with the alcohol extract concentrate, concentrated to a relative density of 1.03-1.25 at 40°C-60°C, and dried under vacuum at 50°C-70°C.

[0012] The third object of the present invention is to provide the use of the above-mentioned pharmaceutical composition in the preparation of drugs for inhibiting inflammation and alleviating diabetic nephropathy.

[0013] Preferably, the drug is in the form of oral solution, tablet, capsule or granule.

[0014] The beneficial effects of the present invention are as follows: (1) For the first time, Ginkgo biloba, Cornus officinalis, and Rehmannia glutinosa were combined and modern extraction, refining, and preparation technologies were applied to preserve the active ingredients of the drug combination to the greatest extent possible to prepare a traditional Chinese medicine preparation for the treatment of diabetic nephropathy; (2) According to the principles of Chinese medicine, the various drugs are combined to enhance each other's efficacy. The ginkgo leaf in the prescription has the function of promoting blood circulation, removing blood stasis, and promoting blood circulation. Its main active ingredients are ginkgo flavonoids, bilobalide (BB), ginkgolide A (GA), ginkgolide B (GB) and ginkgolide C (GC). Pharmacological studies have shown that it can effectively improve renal function, blood lipids, blood sugar and other indicators, as the main medicine; Cornus officinalis nourishes the liver and kidney, astringes and consolidates the body, and its main ingredients are loganin, morroniside, ursolic acid, oleanolic acid, etc., which have the effects of lowering blood sugar, protecting kidney function, and anti-oxidation; Chinese yam nourishes the kidney and essence, strengthens the spleen and stomach, and the two are ministerial medicines, which work together to nourish the kidney and strengthen the spleen; with Rehmannia glutinosa and Astragalus membranaceus as auxiliary, Rehmannia glutinosa nourishes blood and yin, nourishes the kidney and strengthens essence, and Astragalus membranaceus produces fluid and nourishes blood, relieves stagnation and relieves numbness; Poria cocos promotes diuresis and eliminates dampness, strengthens the spleen and calms the mind; the Poria cocos polysaccharide it contains lowers blood sugar by improving insulin resistance and promoting insulin secretion, and Poria cocos acid prevents and treats diabetic nephropathy through anti-inflammatory and anti-oxidation. (3) Animal experiments have shown that the pharmaceutical composition of the present invention can significantly increase the level of serum IL-10, significantly reduce the levels of serum MCP-1, IL-12, BUN, and Scr, and effectively improve the symptoms of "three more and one less" in DN mice, alleviate pathological changes, and can better prevent and treat diabetic nephropathy. The present invention is based on the scientific formulation of traditional Chinese medicine theory, and the selected drugs are all Chinese medicines that are both medicinal and edible, safe and effective, without any toxic side effects, and the raw materials are simple and economical. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 The effects on body weight, fasting blood glucose, food intake and urine volume of diabetic nephropathy (DN) model mice; Figure 2To investigate the effects of PD-1 on renal pathological damage and fibrosis in DN model mice.

[0016] in, Figure 1 -A is body weight; Figure 1 -B is fasting blood sugar; Figure 1 -C is food intake; Figure 1 -D is urine volume; Figure 2 -A is HE staining of kidney pathological damage, Figure 2 -B is Masson staining of kidney pathological damage. DETAILED DESCRIPTION Embodiment 1

[0017] Take 200g of ginkgo leaves, 200g of cornus officinalis, 160g of yam, 120g of prepared rehmannia root, 100g of astragalus, and 100g of poria. Among them, ginkgo leaves, cornus officinalis, prepared rehmannia root, and astragalus root are refluxed and extracted twice with 50% ethanol (12 times the weight of the medicinal materials), each time for 1 hour, filtered, and the alcohol extract is combined. The ethanol is recovered under reduced pressure and concentrated to no alcohol taste. The above-mentioned medicinal residues are combined with yam and poria, and decocted twice with 12 times the weight of the medicinal materials. Water is added, each time for 1 hour, and the decoction is combined, filtered, and the filtrate is concentrated under reduced pressure to a crude drug amount equivalent to 0.8g / ml, centrifuged, and the supernatant is combined with the above-mentioned alcohol extract concentrate, concentrated at 50°C to a relative density of 1.10 (50°C), and vacuum dried to obtain 212.2g of dry extract powder. The dry extract powder is taken, and appropriate amounts of soybean oil, beeswax, and soybean lecithin are added to prepare soft capsule contents, a rubber skin is prepared, and a soft capsule is prepared. Embodiment 2

[0018] Take 300g of ginkgo leaves, 200g of cornus officinalis, 160g of yam, 120g of prepared rehmannia root, 100g of astragalus, and 100g of poria. Among them, ginkgo leaves, cornus officinalis, prepared rehmannia root, and astragalus root are refluxed and extracted twice with 50% ethanol (12 times the weight of the medicinal materials), each time for 1 hour, filtered, and the alcohol extract is combined. The ethanol is recovered under reduced pressure and concentrated to no alcohol taste. The above-mentioned medicinal residues are combined with yam and poria, and decocted twice with 12 times the weight of the medicinal materials. Water is added, each time for 1 hour, and the decoction is combined. The filtrate is concentrated under reduced pressure to a crude drug amount equivalent to 0.8g / ml, centrifuged, and the supernatant is combined with the above-mentioned alcohol extract concentrate, concentrated at 50°C to a relative density of 1.10 (50°C), and vacuum dried to obtain 243.4g of dry extract powder. The dry extract powder is taken, and appropriate amounts of soybean oil, beeswax, and soybean lecithin are added to prepare soft capsule contents, a rubber skin is prepared, and a soft capsule is prepared. Embodiment 3

[0019] Take 150g of ginkgo leaf, 200g of cornus officinalis, 160g of yam, 120g of prepared rehmannia root, 100g of astragalus, and 100g of poria. Among them, ginkgo leaf, cornus officinalis, prepared rehmannia root, and astragalus root are extracted with 50% ethanol 12 times the weight of the medicinal materials twice for 1 hour each time, filtered, and the alcohol extract is combined. The ethanol is recovered under reduced pressure and concentrated to no alcohol taste. The above-mentioned medicinal residues are combined with yam and poria, and decocted twice with 12 times the weight of the medicinal materials. Water is added, and the decoction is combined. The decoction is filtered, and the filtrate is concentrated under reduced pressure to a crude drug amount equivalent to 0.8g / ml, centrifuged, and the supernatant is combined with the above-mentioned alcohol extract concentrate, concentrated at 50°C to a relative density of 1.10 (50°C), and vacuum dried to obtain 205.5g of dry extract powder. The dry extract powder is taken, and appropriate amounts of soybean oil, beeswax, and soybean lecithin are added to prepare soft capsule contents, a rubber skin is prepared, and a soft capsule is prepared. Embodiment 4

[0020] Take 600g of ginkgo leaves, 300g of cornus officinalis, 300g of yam, 200g of prepared rehmannia root, 160g of astragalus, and 160g of poria. Among them, ginkgo leaves, cornus officinalis, prepared rehmannia root, and astragalus root are extracted with 70% ethanol 10 times the weight of the medicinal materials twice for 60 minutes each time, filtered, and the alcohol extracts are combined. The ethanol is recovered under reduced pressure and concentrated to no alcohol taste. The above-mentioned medicinal residues are combined with yam and poria, and decocted twice with 12 times the weight of the medicinal materials. Water is added, each time for 1 hour, and the decoction is combined, filtered, and the filtrate is concentrated under reduced pressure to a crude drug amount equivalent to 1g / ml, centrifuged, and the supernatant is combined with the above-mentioned alcohol extract concentrate, concentrated at 60°C to a relative density of 1.20 (50°C), and vacuum dried to obtain 431.5g of dry extract powder. Take the dry extract powder and add an appropriate amount of dextrin, mix well, perform wet granulation, dry at 60°C, and pack into capsules to obtain 900 hard capsules. Embodiment 5

[0021] Take 400g of ginkgo leaves, 400g of cornus officinalis, 300g of yam, 200g of prepared rehmannia root, 200g of astragalus, and 200g of poria. Among them, ginkgo leaves, cornus officinalis, prepared rehmannia root, and astragalus root are refluxed and extracted twice with 50% ethanol 10 times the weight of the medicinal materials, each time for 1 hour, filtered, and the alcohol extract is combined. The ethanol is recovered under reduced pressure and concentrated to no alcohol taste. The above-mentioned medicinal residues are combined with yam and poria, and decocted twice with 12 times the weight of the medicinal materials. Water is added, each time for 60 minutes, and the decoction is combined, filtered, and the filtrate is concentrated under reduced pressure to a crude drug amount equivalent to 0.9g / ml, centrifuged, and the supernatant is combined with the above-mentioned alcohol extract concentrate, concentrated at 60°C to a relative density of 1.05 (50°C), and vacuum dried to obtain 426.7g of dry extract powder. The dry extract powder is mixed with appropriate amounts of powdered sugar and dextrin for wet granulation, dried at 50°C, and 600g of granules are obtained and packaged. Embodiment 6

[0022] Take 250g of ginkgo leaves, 200g of cornus officinalis, 160g of yam, 120g of prepared rehmannia root, 120g of astragalus, and 120g of poria. Among them, ginkgo leaves, cornus officinalis, prepared rehmannia root, and astragalus root are extracted with 60% ethanol 12 times the weight of the medicinal materials twice for 1 hour each time, filtered, and the alcohol extract is combined. The ethanol is recovered under reduced pressure and concentrated to no alcohol taste. The above-mentioned medicinal residues are combined with yam and poria, and decocted twice with 16 times the weight of the medicinal materials. Each time for 60 minutes, the decoction is combined, filtered, and the filtrate is concentrated under reduced pressure to an amount equivalent to 0.9g / ml of the crude drug, centrifuged, and the supernatant is combined with the above-mentioned alcohol extract concentrate, concentrated at 60°C to a relative density of 1.10 (50°C), and vacuum dried to obtain 245.6g of dry extract powder. The dry extract powder is added with dry starch (1:0.1), mixed evenly for wet granulation, dried at 50°C, an appropriate amount of dry starch is added to the dry granules, mixed evenly, and tableted to obtain.

[0023] Comparative Example 1 Take 200g of ginkgo leaves and add 12 times the weight of the medicinal materials 50% ethanol for reflux extraction twice, each time for 1 hour, filter, combine the alcohol extracts, reduce pressure to recover the ethanol and concentrate until there is no alcohol taste, concentrate at 50℃ to a relative density of 1.10 (50℃), reduce pressure and vacuum dry to obtain 48.1g of dry extract powder, take the dry extract powder, add soybean oil, beeswax, and soybean lecithin in appropriate amounts, prepare the contents of soft capsules, prepare rubber skin, and make soft capsules.

[0024] Comparative Example 2 Take 200g of Cornus officinalis and add 12 times the weight of the medicinal material 50% ethanol for reflux extraction twice, each time for 1 hour, filter, combine the alcohol extracts, reduce pressure to recover the ethanol and concentrate until there is no alcohol taste, concentrate at 50℃ to a relative density of 1.10 (50℃), and reduce pressure and vacuum dry to obtain 44.7g of dry extract powder. Take the dry extract powder, add appropriate amounts of soybean oil, beeswax, and soybean lecithin to make soft capsule contents, prepare rubber skin, and make soft capsules.

[0025] In order to verify the effect of the drug of the present invention on diabetic nephropathy in mice, the following experiments were conducted: 1. Materials and Methods 1.1 Sample: Prepare the drug of the present invention according to the above-mentioned Example 1 to obtain dry extract powder; 1.2 Experimental animals: 36 male KK / Ay mice aged 10–12 weeks, weighing 30–40 g, and 6 male C57BL / 6J mice aged 10–12 weeks were provided by Beijing Huafukang Biotechnology Co., Ltd. All animal experiments were performed in the Experimental Animal Center of Nanjing University of Chinese Medicine, with the experimental ethics number: No. 201903A019.

[0026] 1.3 Experimental method: The blood glucose of KK / Ay mice was tested, and those with blood glucose level ≥10 mmol / L were defined as DM mice. After being fed with high-fat and high-sugar diet for 2 weeks, DM mice with 24h urine protein increased by more than 10 times were defined as DN model mice. The DN model mice were randomly divided into 6 groups, B~G, namely DN group, DN+MET group (0.2g / kg), DN+GBE group (0.2g / kg), DN+SZY group (0.2g / kg), DN+ZHW-L (0.1g / kg) group, and DN+ZHW-H (0.2g / kg) group; 6 C57BL / 6J mice fed with ordinary feed were taken as group A (blank control group); wherein, the DN group was the diabetic nephropathy model group, GBE was the dry extract powder prepared by the formula and method of comparative example 1, SZY was the dry extract powder prepared by the formula and method of comparative example 2, ZHW-L was the low-dose group of dry extract powder prepared by the formula and method of embodiment 1, ZHW-H was the high-dose group of dry extract powder prepared by the formula and method of embodiment 1, and MET was the positive drug metformin. The drug was administered by intragastric administration for 8 weeks, once a day, and the blank control group and the DN group were given an equal amount of normal saline. At 0, 4, and 8 weeks of intragastric administration, the mice in each group were weighed, and their fasting blood glucose, 24-hour food intake, and urine volume were detected and recorded. After the last administration, blood was collected from the eye sockets of the mice in each group, and after standing for 0.5 hours, the blood was centrifuged at 3000 r / min for 15 minutes, and the upper serum was aspirated into a 0.5 mL EP tube for later use; at the same time, the mice in each group were killed, and their kidneys on both sides were separated and weighed, and the ratio of their bilateral kidney mass to body weight was calculated.

[0027] The left kidney was placed in 10% formaldehyde fixative for HE and Masson staining. The serum MCP-1, IL-12, IL-10 levels and renal function-related indexes (BUN, Scr) were detected according to the instructions of the detection kit.

[0028] 2. Experimental results 2.1 Effects of the drug of the present invention on body weight, fasting blood glucose, food intake and urine volume of DN mice like Figure 1 -A. Figure 1 -B. Figure 1 -C. Figure 1-D, at 0, 4, and 8 weeks of intragastric administration, the body weight, fasting blood glucose, 24-hour food intake, and urine volume of mice in the DN group were significantly higher than those in the blank control group (P < 0.01); at 8 weeks of intragastric administration, the body weights of mice in the DN+GBE group, DN+SZY group, DN+MET group, DN+ZHW-L group, and DN+ZHW-H group were significantly lower than those in the DN group. The improvement effect of the ZHW-H group was better than that of the SZY group and the GBE group. The results show that the drug of the present invention can effectively improve the symptoms of "three mores and one less" in diabetes.

[0029] 2.2 Effect of the drug of the present invention on the levels of serum chemokines and inflammatory factors in DN mice ELISA was used to detect the levels of MCP-1, IL-12, and IL-10 in mouse serum to observe the changes in chemokines and inflammatory factors. As shown in Table 1, compared with the blank control group, the levels of serum MCP-1 and IL-12 in mice in the DN group were significantly increased, and the level of IL-10 was significantly decreased (P < 0.01). Compared with the DN group, the levels of serum MCP-1 and IL-12 in mice in the DN+GBE group, DN+SZY group, DN+MET group, DN+ZHW-L group, and DN+ZHW-H group were significantly decreased, and the level of IL-10 was significantly increased (P < 0.01). The improvement effect of the ZHW-H group was significantly better than that of the SZY group and the GBE group. The results show that the drug of the present invention can effectively improve the inflammatory damage caused by DN.

[0030] Table 1 Effects on the levels of MCP-1, IL-12, and IL-10 in DN mice (x±s, n=6)

[0031] Group MCP-1 (pg / mL) IL-12 (pg / mL) IL-10 (pg / mL) Group A (blank control group) 13.21±2.65 45.95±4.39 307.01±26.69 Group B (DN Group) 23.12±3.62 68.55±6.20 214.88±22.37 Group C (DN+MET group) 16.38±5.87** 46.98±5.63** 288.41±24.57** Group D (DN+ZHW-L group) 16.01±3.88** 55.81±4.43** 264.52±27.67** Group E (DN+ZHW-H group) 14.58±4.69** 48.59±4.23** 299.57±23.67** Group F (DN+GBE group) 17.22±2.13** 58.42±5.22** 241.19±32.53** Group G (DN+SZY group) 18.41±3.48** 59.57±6.17** 252.67±30.28** 2.3 Effects of the drug of the present invention on renal function-related indices of DN mice ELISA was used to detect BUN and Scr in mouse serum, and the weight of bilateral kidneys was weighed to observe the changes in renal function-related indicators. As shown in Table 2, compared with the blank control group, the serum BUN, Scr and the ratio of bilateral kidney mass to body weight of mice in the DN group were significantly increased (P < 0.01). Compared with the DN group, the serum BUN, Scr and the ratio of bilateral kidney mass to body weight of mice in the DN+GBE group, DN+SZY group, DN+MET group, DN+ZHW-L group, and DN+ZHW-H group were significantly reduced (P < 0.01). The improvement effect of the ZHW-H group was significantly better than that of the SZY group and the GBE group. The results show that the drug of the present invention can effectively improve the renal function damage caused by DN.

[0032] Table 2 Effects on renal function-related indices of DN mice (x±s, n=6)

[0033] Group BUN (mmol / L) Scr (μmol / L) Ratio of bilateral kidney mass to body weight (%) Group A (blank control group) 19.68±4.83 14.42±3.45 4.43±0.53 Group B (DN Group) 36.44±5.42 58.22±8.53 8.45±0.68 Group C (DN+MET group) 25.66±5.14** 36.63±11.12** 5.33±0.32** Group D (DN+ZHW-L group) 26.88±5.34** 36.60±7.22** 5.63±0.64** Group E (DN+ZHW-H) 22.65±4.33** 27.74±7.65** 4.53±0.77** Group F (DN+GBE group) 30.11±4.45** 41.28±8.12** 6.87±0.85** Group G (DN+SZY group) 29.54±5.67** 44.57±7.23** 6.31±0.76** 2.4 Effects of the drug of the present invention on renal pathological damage and fibrosis changes in DN mice HE and Masson staining were used to observe the pathological changes of renal tissue. Figure 2 -A (HE staining) shows that in the blank control group, no obvious lesions were found in the cardiac and renal cortex, the glomerular structure was intact, and there was little inflammatory cell infiltration. Figure 2 -B (MASSON staining) showed that the renal cortical cells in the DN group showed hyperplasia and hypertrophy, and vacuoles were visible. Inflammatory cell infiltration was visible in some interstitial areas. The renal injury score and renal interstitial fibrosis ratio were significantly higher than those in the blank control group. Compared with the DN group, the DN+MET group, DN+ZHW-L group, and DN+ZHW-H group significantly alleviated histopathological changes. Although the DN+GBE group and DN+SZY group could also alleviate histopathological changes, the effect was significantly worse than that of the DN+MET group, DN+ZHW-L group, and DN+ZHW-H group. The effect of the ZHW-H group was slightly better than that of the ZHW-L group, and significantly better than that of the GBE group and the SZY group. The results showed that the drug of the present invention can effectively improve the renal injury and renal interstitial fibrosis of DN.

[0034] Through the above embodiments, the present invention has fully and effectively achieved the purpose of the invention. People familiar with the art should understand that the present invention includes but is not limited to the contents described in the drawings, attached tables and the above embodiments. Any modification that does not deviate from the function and principle of the present invention will be included in the scope of the claims.

Claims

1. A pharmaceutical composition for improving diabetic nephropathy, characterized in that: The invention comprises the following raw materials by weight: 10-20 parts of ginkgo leaves, 10-20 parts of cornus officinalis, 8-15 parts of yam, 6-10 parts of rehmannia root, 5-8 parts of astragalus root and 5-8 parts of tuckahoe.

2. The pharmaceutical composition for improving diabetic nephropathy according to claim 1, characterized in that: The weight ratio of the ginkgo leaves to the cornus officinalis is 1:

1.

3. The pharmaceutical composition for improving diabetic nephropathy according to claim 1, characterized in that: The invention comprises the following raw materials by weight: 10 parts of ginkgo leaves, 10 parts of cornus officinalis, 8 parts of yam, 6 parts of rehmannia root, 5 parts of astragalus root and 5 parts of tuckahoe.

4. The method for preparing the pharmaceutical composition according to any one of claims 1 to 3, characterized in that: The following steps are involved: (1) Ginkgo biloba leaves, Cornus officinalis, Rehmannia root and Astragalus membranaceus are extracted by reflux with ethanol, and the ethanol extract is recovered by vacuum decompression until there is no alcohol taste, and concentrated to obtain an ethanol extract concentrate and medicinal residues for later use; (2) The above-mentioned drug residues, yam and poria are boiled in water, the decoction is filtered, the filtrate is concentrated, centrifuged, the supernatant is collected, and after further concentration, it is combined with the alcohol extract concentrate of step (1), concentrated, and dried to obtain an extract powder, thereby obtaining a pharmaceutical composition.

5. The method for preparing the pharmaceutical composition according to claim 4, characterized in that: The weight of ethanol added in step (1) is 8-16 times the weight of the medicinal material, and the concentration is 30-80%. The extraction is performed by reflux for 2-3 times, each time for 1.0-1.5 hours.

6. The method for preparing the pharmaceutical composition according to claim 4, characterized in that: In step (2), the amount of water added is 8-16 times the weight of the medicinal material, and the decoction is performed twice, each time for 1.0-1.5 hours. The decoctions are combined and concentrated to a crude drug amount of 0.8 g / ml-1.2 g / ml, centrifuged, and the supernatant is combined with the alcohol extract concentrate, concentrated to a relative density of 1.03-1.25 at 40°C-60°C, and dried under vacuum at 50°C-70°C.

7. Use of the pharmaceutical composition according to any one of claims 1 to 3 in the preparation of a medicament for treating diabetic nephropathy.

8. Use of the pharmaceutical composition according to claim 7 in the preparation of a medicament for treating diabetic nephropathy, wherein the medicament is in the form of oral liquid, tablet, capsule or granule.

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