A traditional Chinese medicine composition for diabetic nephropathy, a preparation method thereof and application thereof

Abstract

The application provides a traditional Chinese medicine composition for diabetic nephropathy and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 20-50 parts of radix astragali, 10-15 parts of red peony root, 8-12 parts of sileris acutangae, 25-35 parts of porcine-fried atractylodes, 25-35 parts of imperata cylindrica, 10-20 parts of chamaerops and 10-20 parts of wine female ligustrum fruit. The traditional Chinese medicine composition is used in combination, can tonify deficiency of the two main organs of the spleen and the kidney, can eliminate dampness and heat, and can prevent and / or treat diabetic nephropathy.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of traditional Chinese medicine, and provides a traditional Chinese medicine composition for diabetic nephropathy and a preparation method and application thereof. BACKGROUND

[0002] Diabetic nephropathy is one of the complications of diabetes and is an important cause of end-stage renal failure and kidney dialysis. In clinical treatment, Western medicine mainly focuses on regulating blood glucose, blood lipids and blood pressure, and the progress of glomerular sclerosis is delayed by reducing blood pressure, blood glucose and blood lipids through the use of angiotensin-converting enzyme inhibitors (ACEI) / angiotensin II receptor blockers (ARB), hypoglycemic drugs and statins. The methods include reducing blood pressure by using ACEI and ARB drugs, reducing blood glucose by using biguanide drugs such as metformin and α-glucosidase inhibitors such as dapagliflozin, and reducing blood lipids and anti-atherosclerosis by using statins, so as to regulate glucose and lipid metabolism and delay glomerular sclerosis. However, there are still limitations such as uncertain drug efficacy and adverse drug reactions. In addition, the therapeutic effect of pure Western medicine is not satisfactory, especially in terms of controlling urinary protein, and the existing drugs all have certain degree of adverse reactions, and the disease condition of some patients develops.

[0003] A large number of studies have shown that traditional Chinese medicine has remarkable curative effect in improving symptoms and delaying the progress of diabetic nephropathy. Traditional Chinese medicine believes that "qi and yin deficiency causing blood stasis and stagnation in kidney collaterals" is the basic pathogenesis of diabetic nephropathy, and different pathological characteristics and pathogenesis changes are shown in different stages of diabetic nephropathy. On the basis of syndrome differentiation and treatment, the treatment is also divided into stages and mainly focuses on tonifying the spleen and kidney, promoting blood circulation and resolving toxins, and removing dampness and turbidity. In addition, the treatment of special prescriptions is based on the pathogenesis of qi and yin deficiency and spleen and kidney deficiency, and mainly focuses on tonifying qi and yin, tonifying the spleen and kidney, and resolving stasis. In addition, traditional Chinese medicine external treatment (enema, acupuncture, foot bath, etc.) also achieves remarkable curative effect in clinic.

[0004] Chinese patent CN104721467B discloses a traditional Chinese medicine composition for treating diabetic nephropathy, which is made of raw medicinal materials: 100 parts by weight of radix astragali, 20-40 parts by weight of ligustrum lucidum, 25-45 parts by weight of atractylodes, 40-60 parts by weight of chamaepermum, 40-60 parts by weight of abelmoschus flower, 30-50 parts by weight of yam, 35-55 parts by weight of red peony root, and 15-35 parts by weight of goldthread. The traditional Chinese medicine composition has good therapeutic effect on diabetic nephropathy, especially early diabetic nephropathy. However, it contains abelmoschus flower and goldthread, which are not suitable for long-term use by people with spleen-stomach deficiency and cold, and the therapeutic effect on diabetic nephropathy needs to be further improved.

[0005] Some traditional Chinese medicine compounds or single herbs such as Huangqi, Ginkgo, Leigongteng, Dahuang, etc. have been proved to be able to strengthen the protection of the kidney of patients, regulate blood glucose and blood lipid, reduce urinary protein, delay interstitial fibrosis, and improve clinical symptoms, and even have a reverse effect on early diabetic nephropathy. However, it is still in the initial research stage, lacks systematic research and clinical data support, and therefore it is necessary to further study the compatibility of each traditional Chinese medicine ingredient to promote the standardization of traditional Chinese medicine in preventing and treating diabetic nephropathy and further improve the treatment effect of traditional Chinese medicine on diabetic nephropathy. SUMMARY

[0006] In view of the problems in the prior art, the present application provides a traditional Chinese medicine composition for diabetic nephropathy and a preparation method and application thereof. The traditional Chinese medicine composition has a significant effect on early clinical treatment of diabetic nephropathy on the basis of traditional Chinese medicine dialectical treatment, reduces urinary protein, delays the development of the disease, and even reverses the occurrence and development of early diabetic nephropathy through timely treatment in the early stage of diabetic nephropathy.

[0007] The technical scheme of the present application is as follows:

[0008] In a first aspect of the present application, a traditional Chinese medicine composition for diabetic nephropathy is provided.

[0009] The traditional Chinese medicine composition comprises the following raw materials in parts by weight: Huangqi 20-50 parts, Chishao 10-15 parts, Fangfeng 8-12 parts, Futocha Baishu 25-35 parts, Baimaogen 25-35 parts, Jinyingzi 10-20 parts, and Jiunvzizi 10-20 parts.

[0010] Preferably, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: Huangqi 25-35 parts, Chishao 11-13 parts, Fangfeng 9-11 parts, Futocha Baishu 28-32 parts, Baimaogen 28-32 parts, Jinyingzi 12-18 parts, and Jiunvzizi 12-18 parts.

[0011] More preferably, the traditional Chinese medicine composition comprises the following raw materials in parts by weight: Huangqi 30 parts, Chishao 12 parts, Fangfeng 10 parts, Futocha Baishu 30 parts, Baimaogen 30 parts, Jinyingzi 15 parts, and Jiunvzizi 15 parts.

[0012] Spleen-kidney deficiency is the key pathogenesis of diabetic nephropathy. As the congenital basis, the kidney contains true yang and true yin, and the spleen is the acquired basis. Spleen deficiency cannot transport and transform, the function of separating clear and turbid decreases, and subtle essence cannot be excreted as proteinuria. The spleen and the kidney are mutually dependent on each other, the transport and transformation of the spleen depends on the warming and steaming of kidney yang, and the essence in the kidney depends on the nutrient of the water and grain essence transported and transformed by the spleen. Therefore, kidney deficiency fails to store essence, essence leaks, kidney yang deficiency, fire does not generate earth, and spleen qi deficiency. Earth generates gold, and spleen earth does not generate gold, resulting in lung qi deficiency, essence cannot return to the lung, the lung loses its function of diffusion and exhalation, and cannot transport essence to the whole body. If the lung is affected by wind, the lung qi is blocked by evil, the diffusion and exhalation are not smooth, and essence and substance directly go to the bladder to form urine turbidity.

[0013] The functions of each component in the traditional Chinese medicine composition of the present application are as follows:

[0014] Huangqi is Gan-wen and returns to both the spleen and lung channels, has the functions of benefiting qi and ascending yang, and promoting water and reducing swelling. It can not only tonify the spleen and benefit qi, but also diuretic and reduce swelling. It is not only the main medicine for tonifying the spleen and benefiting qi, but also the main medicine for qi deficiency and edema. It is said in Benjing Feng Yuan that "Huangqi, although it is warm and tonic, can regulate blood and collaterals, and can be used without affecting stagnation. Huangqi can benefit qi with ginseng." Modern pharmacological studies show that the medicinal components of Huangqi mainly include Huangqi polysaccharides, Huangqi saponins, flavonoids, amino acids, alkaloids, etc. Among them, Huangqi polysaccharides, Huangqi saponins and flavonoids are the main effective components for treating diabetic nephropathy. The active components of Huangqi for treating diabetic nephropathy targets and pathways: mainly through regulating endoplasmic reticulum stress, regulating glucose and lipid metabolism, reducing inflammation, improving insulin resistance, reducing cell apoptosis, and inhibiting the progression of renal fibrosis to improve kidney damage.

[0015] Modern pharmacological studies show that Chishao contains terpenes and their glycosides, flavonoids and their glycosides, tannins, phenolic acids and their glycosides, polysaccharides, volatile oils and other compounds. It has the effects of reducing blood sugar, reducing insulin resistance, regulating lipid metabolism disorders, improving hemodynamic status, and inhibiting inflammatory response. It can improve glomerular sclerosis and protect kidney tissue and function, thereby reducing the occurrence and delaying the progression of diabetic nephropathy.

[0016] Fangfeng is pungent and sweet, and slightly warm. It enters the bladder, liver and spleen channels. Fangfeng disperses and warms, and can carry the function of Huangqi to supplement qi throughout the body. Supplementing qi and ascending yang can assist the operation and transformation of spleen qi, and the gasification and fixation of kidney qi, so that the essence ascends without excretion. When used with Baizhu, it can overcome dampness, promote the ascending of clear yang, and the dampness is removed, the spleen and stomach are transformed, the evil is removed, the essence is fixed, and the effect of reducing urinary protein is achieved.

[0017] Futao Baizhu is bitter and warm, and can invigorate the spleen and stomach, cultivate the middle and control water, so that the spleen qi can be transported, the water and dampness can be transformed, and the ascending and descending of the spleen and stomach is in order. Modern pharmacological studies show that its main effective components include volatile oil, internal fat components and Baizhu polysaccharides, among which Baizhu volatile oil can effectively reduce blood sugar and blood lipids. The addition of Jinyingzi can supplement the kidney and fix the essence, and fill the kidney essence. When the kidney qi is fixed and the essence is filled, the urinary protein is reduced.

[0018] Modern pharmacological studies show that Jinyingzi is rich in flavonoids, polysaccharides, saponins, tannins and other active substances. Among them, Jinyingzi flavonoids have antioxidant, immune enhancement, antibacterial and hypolipidemic effects.

[0019] Nuzhenshi is sweet and bitter, and cool. It tonifies the liver and kidney, and also has astringent effect. Clinical studies have shown that it can delay kidney failure and improve kidney function. Pharmacological studies have also shown that it has anti-inflammatory, antioxidant, immune regulation, and treatment of diabetes, etc.

[0020] Rosae Laevigatae Fructus is stronger in astringency and deficiency, and is used with Ligustri Lucidi Fructus, so that it can treat proteinuria by tonifying kidney qi and consolidating kidney essence.

[0021] When tonifying deficiency, attention should be paid to damp-heat or heat-toxin evil, and the combination of tonifying and purging should be used, and the addition of Imperata Cylindrae Rhizoma for clearing heat and promoting diuresis. The active components of Imperata Cylindrae Rhizoma mainly include polysaccharides, anemarrhena, organic acids, imperatorin, and campesterol. Pharmacological studies show that the polysaccharides of Imperata Cylindrae Rhizoma have the effects of improving glucose tolerance, reducing glycated serum protein, promoting the synthesis of liver glycogen, regulating blood lipid metabolism disorder, and reducing urinary protein.

[0022] The combination of all the prescriptions can tonify the deficiency of the spleen and kidney, and the combination of purging and tonifying can not forget the root of the spleen and kidney, and the combination of tonifying and purging can not forget the treatment of damp-heat. If the consolidation is appropriate, the essence of the spleen and kidney will be sufficient, and if the consolidation is appropriate, the proteinuria will gradually decrease.

[0023] In some more preferred embodiments of the present application, the traditional Chinese medicine composition further comprises one or more of Curcuma Longa, Fried Sphoderm, Periostracum Cicadae, Radix Anisati, Pericarpium Citri Reticulatae, Fructus Aurantii Immaturus, Bamboo Shrub, Fried Jujube Seed, Caulis Polygoni Multiflori, Calcined Ossis Bezoar, Calcined Oyster Shell, Flos Albiziae, and Daidai.

[0024] Preferably, the traditional Chinese medicine composition is prepared from the following raw materials by weight: 30 parts of Radix Paeoniae Alba, 12 parts of Radix Paeoniae Rubra, 10 parts of Radix Saposhnikoviae, 30 parts of Poria Cocos, 30 parts of Imperata Cylindrae Rhizoma, 15 parts of Rosae Laevigatae Fructus, 15 parts of Ligustri Lucidi Fructus, 10 parts of Curcuma Longa, 15 parts of Fried Sphoderm, and 10 parts of Periostracum Cicadae. This preferred embodiment can improve diabetic nephropathy, and also improve symptoms such as aversion to cold, heat, chest and stomach distension, and vomiting and diarrhea.

[0025] Preferably, the traditional Chinese medicine composition is prepared from the following raw materials by weight: 30 parts of Radix Paeoniae Alba, 12 parts of Radix Paeoniae Rubra, 10 parts of Radix Saposhnikoviae, 30 parts of Poria Cocos, 30 parts of Imperata Cylindrae Rhizoma, 15 parts of Rosae Laevigatae Fructus, 15 parts of Ligustri Lucidi Fructus, 9 parts of Radix Anisati, 10 parts of Pericarpium Citri Reticulatae, 20 parts of Fructus Aurantii Immaturus, and 10 parts of Bamboo Shrub. This preferred embodiment can improve diabetic nephropathy, and also improve symptoms such as dizziness, palpitation, vomiting, hiccups, and dizziness.

[0026] Preferably, the traditional Chinese medicine composition is prepared from the following raw materials by weight: 30 parts of Radix Paeoniae Alba, 12 parts of Radix Paeoniae Rubra, 10 parts of Radix Saposhnikoviae, 30 parts of Poria Cocos, 30 parts of Imperata Cylindrae Rhizoma, 15 parts of Rosae Laevigatae Fructus, 15 parts of Ligustri Lucidi Fructus, 30 parts of Fried Jujube Seed, and 30 parts of Caulis Polygoni Multiflori. This preferred embodiment can improve diabetic nephropathy, and also improve symptoms such as insomnia and dreaminess.

[0027] Preferably, the traditional Chinese medicine composition is prepared from the following raw materials by weight: 30 parts of Radix Astragali, 12 parts of Radix Paeoniae Rubra, 10 parts of Radix Saposhnikoviae, 30 parts of Poria Cocos Roasted with Wheat Bran, 30 parts of Imperata Cylindra, 15 parts of Rosa Laevigata Michx, 15 parts of Fructus Ligustri Lucidi, 30 parts of Ossis Bezoar Calcined, and 30 parts of Ossis Conchi Testae Calcined. The preferred embodiment improves diabetic nephropathy and also improves symptoms such as night sweating.

[0028] Preferably, the traditional Chinese medicine composition is prepared from the following raw materials by weight: 30 parts of Radix Astragali, 12 parts of Radix Paeoniae Rubra, 10 parts of Radix Saposhnikoviae, 30 parts of Poria Cocos Roasted with Wheat Bran, 30 parts of Imperata Cylindra, 15 parts of Rosa Laevigata Michx, 15 parts of Fructus Ligustri Lucidi, 30 parts of Ossis Bezoar Calcined, and 30 parts of Ossis Conchi Testae Calcined. The preferred embodiment improves diabetic nephropathy and also improves symptoms such as night sweating.

[0029] In a second aspect, the present application provides a preparation method of the traditional Chinese medicine composition, comprising the following steps:

[0030] (1) grinding and sieving all the raw materials for use;

[0031] (2) adding the raw materials of Radix Astragali, Radix Saposhnikoviae, Poria Cocos Roasted with Wheat Bran, Imperata Cylindra, and Fructus Ligustri Lucidi into an ethanol solution, performing alcohol extraction, and filtering to obtain filtrate A;

[0032] (3) adding the raw materials of Radix Paeoniae Rubra and Rosa Laevigata Michx into water, performing water extraction, adding ethanol for precipitation after the end of the water extraction, and filtering to obtain filtrate B;

[0033] (4) combining the filtrate A and the filtrate B, and concentrating to obtain the traditional Chinese medicine composition.

[0034] Further, in step (2), the concentration of the ethanol solution is 50-80 vol%; the number of alcohol extraction is 1-4 times, and the extraction time of each time is 1-2 h; the solid-liquid ratio of the raw materials to the ethanol solution is 1 g:5-10 mL.

[0035] Further, in step (3), the number of water extraction is 1-4 times, and the extraction time of each time is 1-2 h; the solid-liquid ratio of the raw materials to water is 1 g:10-20 mL.

[0036] In a third aspect, the present application provides the use of the traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the above preparation method in the preparation of a medicine for preventing and / or treating diabetic nephropathy.

[0037] Further, the diabetic nephropathy is type 2 diabetic nephropathy.

[0038] Further, the type 2 diabetic nephropathy is caused by high-fat and high-sugar streptozotocin.

[0039] In a fourth aspect, the present application provides a traditional Chinese medicine preparation, characterized by comprising the traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the above preparation method.

[0040] Further, the dosage form of the traditional Chinese medicine preparation is any one of tablets, granules, capsules, decoctions and pastes.

[0041] For the prior art, the beneficial effects of the present application are:

[0042] Radix Astragali is the monarch, greatly tonifying primordial qi, promoting spleen qi transformation, benefiting the defensive qi to resist external pathogens, tonifying kidney qi to transform water and liquid, tonifying spleen qi to transform water and dampness, tonifying lung qi to regulate water passage, which can achieve the effect of diuresis and swelling. Radix Paeoniae Rubra is used as the minister, promoting blood circulation and removing blood stasis, unblocking meridians, and the combination of Radix Astragali and Radix Paeoniae Rubra makes qi sufficient and blood unobstructed. Radix Saposhnikoviae is used as the assistant, lifting yang qi, transforming dampness, tonifying qi, lifting yang, assisting spleen qi transformation, ascending clear, and making essence-ming upward without excretion, which achieves the effect of reducing proteinuria. Bupleurum chinense is warm in nature, and returns to the spleen and stomach channels, which is good at diuresis and dampness. Fructus Rosae Laevigatae and Ligustri Lucidi Fructus tonify the kidney and astringe essence, and benefit qi and consolidate loss. Radix Imperatae clears heat and cools blood, and nourishes yin and generates fluid. The combination of all the above can tonify the deficiency of the two main organs of the spleen and kidney, and the method of purging the excess without forgetting the tonification of the spleen and kidney, and the method of tonifying deficiency without forgetting the treatment of dampness and heat. If the protection is appropriate, the essence of the spleen and kidney will be sufficient, and the proteinuria will gradually decrease. DETAILED DESCRIPTION

[0043] In order to make the purpose, technical scheme and advantages of the embodiments of the present application more clear, the technical scheme in the embodiments of the present application will be described clearly and completely below. Obviously, the described embodiments are part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application. It is worth mentioning that the raw materials used in the present application are all ordinary commercially available products, and their sources are not specifically limited.

[0044] Among them, the traditional Chinese medicine raw materials Ligustri Lucidi Fructus and Bupleurum chinense used in the examples are purchased from Hebei Baicaokangshen Pharmaceutical Co., Ltd.

[0045] Example 1

[0046] A traditional Chinese medicine composition, the prescription is: Radix Astragali 30g, Radix Paeoniae Rubra 12g, Radix Saposhnikoviae 10g, Bupleurum chinense 30g, Radix Imperatae 30g, Fructus Rosae Laevigatae 15g and Ligustri Lucidi Fructus 15g.

[0047] The specific preparation method is as follows:

[0048] The raw materials in the prescription are ground and passed through a 100-mesh screen. The amount of Huangqi, Fangfeng, bran-fried Baizhu, Baomahuang and Jiunvzhi prescribed is taken and added to 75% ethanol solution at a solid-liquid ratio of 1 g:10 mL. Decoction is performed for 3 times, 2 hours each time. The filtrate is combined to obtain the ethanol extract (recovery of ethanol until there is no alcohol taste). The amount of Chishao and Jinyingzi prescribed is taken and added to water at a solid-liquid ratio of 1 g:20 mL. Decoction is performed for 3 times, 2 hours each time. Ethanol is added until the amount of ethanol in the solution is 60% by volume. The supernatant is recovered to obtain the ethanol extract. The ethanol extract is combined with the above ethanol extract. Concentration is performed until the concentration is 5 g crude drug per g extract, to obtain the product.

[0049] Example 2

[0050] A traditional Chinese medicine composition, the prescription of which is as follows: Huangqi 20 g, Chishao 10 g, Fangfeng 8 g, bran-fried Baizhu 25 g, Baomahuang 25 g, Jinyingzi 10 g and Jiunvzhi 10 g.

[0051] The specific preparation method is as follows:

[0052] The raw materials in the prescription are ground and passed through a 100-mesh screen. The amount of Huangqi, Fangfeng, bran-fried Baizhu, Baomahuang and Jiunvzhi prescribed is taken and added to 50% ethanol solution at a solid-liquid ratio of 1 g:8 mL. Decoction is performed for 2 times, 2 hours each time. The filtrate is combined to obtain the ethanol extract (recovery of ethanol until there is no alcohol taste). The amount of Chishao and Jinyingzi prescribed is taken and added to water at a solid-liquid ratio of 1 g:15 mL. Decoction is performed for 2 times, 2 hours each time. Ethanol is added until the amount of ethanol in the solution is 60% by volume. The supernatant is recovered to obtain the ethanol extract. The ethanol extract is combined with the above ethanol extract. Concentration is performed until the concentration is 5 g crude drug per g extract, to obtain the product.

[0053] Example 3

[0054] A traditional Chinese medicine composition, the prescription of which is as follows: Huangqi 50 g, Chishao 15 g, Fangfeng 12 g, bran-fried Baizhu 35 g, Baomahuang 35 g, Jinyingzi 20 g and Jiunvzhi 20 g.

[0055] The specific preparation method is as follows:

[0056] The raw materials in the prescription are ground and passed through a 100-mesh screen. The amount of Huangqi, Fangfeng, bran-fried Baizhu, Baomahuang and Jiunvzhi prescribed is taken and added to 75% ethanol solution at a solid-liquid ratio of 1 g:10 mL. Decoction is performed for 4 times, 2 hours each time. The filtrate is combined to obtain the ethanol extract (recovery of ethanol until there is no alcohol taste). The amount of Chishao and Jinyingzi prescribed is taken and added to water at a solid-liquid ratio of 1 g:20 mL. Decoction is performed for 4 times, 2 hours each time. Ethanol is added until the amount of ethanol in the solution is 60% by volume. The supernatant is recovered to obtain the ethanol extract. The ethanol extract is combined with the above ethanol extract. Concentration is performed until the concentration is 5 g crude drug per g extract, to obtain the product.

[0057] Example 4

[0058] A traditional Chinese medicine composition, the prescription is: Radix Astragali 30g, Red Root 12g, Wind-Preventive Herb 10g, Bran-Fried Atractylodes 30g, White Lily Root 30g, Chokeberry 15g, Wine Female Privet Fruit 15g, Fried Jujube Seed 30g and Caulis Polygoni Multiflori 30g.

[0059] The specific preparation method is as follows:

[0060] The raw materials in the prescription are crushed and passed through a 100 mesh sieve. The prescribed amount of Radix Astragali, Wind-Preventive Herb, Bran-Fried Atractylodes, White Lily Root, Wine Female Privet Fruit, Fried Jujube Seed and Caulis Polygoni Multiflori are added to 75% ethanol solution at a solid-liquid ratio of 1g:10mL, and decocted for 3 times, 2h each time. The filtrates are combined to obtain the ethanol extract (recovery of ethanol until no alcohol taste). The prescribed amount of Red Root and Chokeberry are added to water at a solid-liquid ratio of 1g:20mL, and decocted for 3 times, 2h each time. Ethanol is added to the solution until the ethanol content is 60%. The supernatant is recovered to no alcohol taste. The ethanol extract and the supernatant are combined, and concentrated to 6.67g crude drug / g extract, to obtain the product.

[0061] Comparative Example 1

[0062] A traditional Chinese medicine composition, the prescription is: Radix Astragali 100g, Female Privet Fruit 33.3g, Atractylodes 33.3g, Chokeberry 50g, Abelmoschus Flower 50g, Rhizoma Dioscoreae Complanatae 40g, Red Root 40g and Coptis 20g.

[0063] The preparation method is as follows:

[0064] The Female Privet Fruit, Atractylodes and Coptis are added to 8.6 times the amount of 70% ethanol solution and extracted for 2 times, 2h each time. The extraction liquid is combined, and the ethanol is recovered to no alcohol taste to obtain the ethanol extract. The Red Root, Radix Astragali, Abelmoschus Flower, Rhizoma Dioscoreae Complanatae and Chokeberry are added to 10.8 times the amount of water and extracted for 2 times, 1.5h each time. The extraction liquid is combined, and concentrated to a relative density of 1.15. Ethanol is added to make the ethanol content 60%, mixed, and placed for 24h. The supernatant is taken, and the ethanol is recovered to no alcohol taste to obtain the water extract concentrate. The ethanol extract and the water extract concentrate are mixed, and concentrated to 5g crude drug / g extract, to obtain the product.

[0065] Comparative Example 2

[0066] The difference from Example 1 is only in the prescription of the traditional Chinese medicine composition, specifically: Radix Astragali 25g, Red Root 17g, Wind-Preventive Herb 10g, Bran-Fried Atractylodes 30g, White Lily Root 30g, Chokeberry 15g and Wine Female Privet Fruit 15g.

[0067] Comparative Example 3

[0068] The difference from Example 1 is only in the prescription of the traditional Chinese medicine composition, specifically: Radix Astragali 30g, Red Root 8g, Wind-Preventive Herb 14g, Bran-Fried Atractylodes 30g, White Lily Root 30g, Chokeberry 15g and Wine Female Privet Fruit 15g.

[0069] Comparative Example 4

[0070] The difference from Example 1 is only in the prescription of the traditional Chinese medicine composition, specifically: Radix Astragali 30 g, Abelmoschus flower 12 g, Saposhnikovia divaricata 10 g, Poria Cocos 30 g, Imperata Cylindra 30 g, Chamaerops 15 g, and Fructus Ligustri Lucidi 15 g.

[0071] Comparative Example 5

[0072] The difference from Example 1 is only in the prescription of the traditional Chinese medicine composition; specifically: Radix Astragali 30 g, Red Peony Root 12 g, Saposhnikovia divaricata 10 g, Poria Cocos 30 g, Abelmoschus flower 30 g, Chamaerops 15 g, and Fructus Ligustri Lucidi 15 g.

[0073] Comparative Example 6

[0074] The difference from Example 1 is only in the prescription of the traditional Chinese medicine composition; specifically: Radix Astragali 30 g, Red Peony Root 12 g, Alisma 10 g, Poria Cocos 30 g, Imperata Cylindra 30 g, Chamaerops 15 g, and Fructus Ligustri Lucidi 15 g.

[0075] Experimental Example 1: Therapeutic effect on operation + high-fat + STZ-induced diabetic nephropathy model rats

[0076] I. Experimental drugs and reagents:

[0077] The test drug is the traditional Chinese medicine composition prepared in Examples 1-4 and Comparative Examples 1-6, which is dissolved and prepared into a concentration of 0.25 g of crude drug / mL with citric acid buffer;

[0078] The positive control drug is valsartan capsules, 80 mg / pill, purchased from Beijing Novartis Pharmaceutical Co., Ltd.;

[0079] High-fat feed formula: composed of sucrose 20%, lard oil 10%, cholesterol 2.5%, cholate 1%, and ordinary feed 66.5% (i.e. type II diabetes model feed) by mass percentage, purchased from Beijing Keao Hesuoliliao Feed Co., Ltd.;

[0080] Streptozotocin (STZ, product number: S0130-5g) was purchased from Sigma Company;

[0081] Citric acid buffer was purchased from National Pharmaceutical Group Chemical Reagent Co., Ltd.;

[0082] Urinary protein quantitative kit (item number: C035-2-1), creatinine (Cr) kit (item number: C011-2-1), glutamic-pyruvic transaminase (ALT) assay kit (item number: C009-2-1), glutamic-oxalacetic transaminase (AST) assay kit (item number: C010-2-1), total cholesterol (CHO) assay kit (item number: A111-1-1), triglyceride (TG) assay kit (item number: A110-1-1), high-density lipoprotein (HDL-C) assay kit (item number: A112-1-1), low-density lipoprotein (LDL-C) assay kit (item number: A113-1-1), total protein (TP) assay kit (item number: A045-4-2), albumin (Alb) assay kit (item number: A028-2-1) were all purchased from Nanjing Jiancheng Biological Institute.

[0083] II. Experimental animals:

[0084] 160 Wistar rats, SPF level, male, body weight 180-200 grams, purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., license number: SCXK (Jing) 2012-0001; fed in the SPF animal room of the Xiyuan Hospital of China Academy of Chinese Medical Sciences.

[0085] III. Experimental methods:

[0086] The rats were adaptively fed for 4 days, and randomly divided into 16 groups, 10 rats in each group, namely, sham operation group, blank control group, model group, positive control group and traditional Chinese medicine groups 1-12. The rats in each group were first subjected to unilateral (left) kidney ligation (among them, the unilateral kidney of the sham operation group was directly sutured after incision), and after recovery for 1 week, the sham operation group and the blank control group were given ordinary feed, and the rest of the groups were given high-fat feed, and fed for 4 weeks. The intraperitoneal glucose tolerance (IPGTT), serum total cholesterol (CHO) and triglyceride (TG) were determined. Compared with the sham operation group and the blank control group, the IPGTT and CHO of the rest of the groups were increased, which was statistically significant (P<0.01), indicating that abnormal glucose metabolism was induced. The model group, the positive control group and the traditional Chinese medicine groups 1-12 were again injected with 1% STZ 25mg / kg (solvent: citric acid buffer) by intraperitoneal injection. After 72 hours, the animals were fasted for 3 hours, and the tail tip blood was taken for rapid blood glucose, which was all greater than 12.5mmol / L. The operation + high-fat + STZ induced diabetic nephropathy model was completed. The blank control group was injected with the same amount of citric acid buffer, and the sham operation group was not treated.

[0087] The rats in each group were then administered, positive control group: valsartan capsules 0.01 g / kg; traditional Chinese medicine group 1: 2.5 g / kg of the traditional Chinese medicine composition in Example 1; traditional Chinese medicine group 2: 5 g / kg of the traditional Chinese medicine composition in Example 1; traditional Chinese medicine group 3: 10 g / kg; traditional Chinese medicine groups 4-6: 5 g / kg of the traditional Chinese medicine composition in Examples 2-4, respectively; traditional Chinese medicine groups 7-12: 5 g / kg of the traditional Chinese medicine composition in Comparative Examples 1-6, respectively; the sham operation group and the blank control group were administered the same volume of distilled water; once a day, for 8 consecutive weeks.

[0088] 24 hours after the last administration, urine was taken and the urine protein and urine creatinine content was determined; at the same time, the rats were sacrificed, blood was taken from the abdominal cavity and vein, and the serum ALT, AST, CHO, TG, HDL-C, LDL-C, TP, and Alb were detected. The experimental data are represented by t test was used for data between groups, and P<0.05 was considered to be statistically significant.

[0089] Four, experimental results

[0090] 1. Effect on urine protein and urine creatinine of rats

[0091] The results of the urine protein and urine creatinine content test of the rats in each group 24 hours later are shown in Table 1. It can be seen that, compared with the sham operation group and the blank control group, the urine protein content of the rats in the model group was significantly increased and the urine creatinine was significantly decreased (both P<0.01, statistically significant) after 8 weeks of modeling, the liver function was impaired, and the diabetic nephropathy model was successfully modeled. The traditional Chinese medicine composition (5 g / kg) of the application can reduce the excretion of urine protein and promote the excretion of urine creatinine, and the effect of promoting the excretion of urine creatinine is better than that of the positive control drug valsartan capsules (P<0.05, statistically significant), close to the level of the sham operation group and the blank control group. Compared with administration group 2 (administered with 5 g / kg of the traditional Chinese medicine composition in Example 1), administration groups 7-12 had higher urine protein excretion and lower urine creatinine excretion, and both were statistically significant.

[0092] Table 1 Results of urine protein and urine creatinine of diabetic nephropathy rats

[0093] Urine protein (mg) Urine creatinine (mmol / L) Sham operation group 16.84±2.15 3.288±0.842 Blank control group 18.11±3.28 3.351±1.055 Model group 54.96 ± 8.51 **## ]] 1.579 ± 0.429 **## ]] Positive control group 33.86 ± 5.30 *& ]] 2.014 ± 0.386 #& ]] Dosing group 1 42.65 ± 5.09 **&△ ]] 2.531 ± 0.650 #&& ]] Dosing group 2 37.12 ± 5.15 *&& ]] 2.954 ± 0.811 &&△ ]] Dosing group 3 30.14 ± 4.28 *&& ]] 3.112 ± 0.782 &&△ ]] Dosing group 4 42.38 ± 5.84 **&△ ]] 2.355 ± 0.495 #& ]] Dosing group 5 43.15 ± 6.03 **&△ ]] 2.108 ± 0.502 #& ]] Dosing group 6 38.44 ± 4.24 *&& ]] 2.950 ± 0.712 &&△ ]] Dosing group 7 51.82 ± 7.44 **△△□□ ]] 2.431 ± 0.605 #&□ ]] Dosing group 8 53.03 ± 6.84 **△△□□ ]] 1.852 ± 0.545 ##□□ ]] Dosing group 9 49.25 ± 6.06 **△△□□ ]] 2.011 ± 0.617 #&□ ]] Dosing group 10 50.25 ± 7.05 **△△□□ ]] 1.874 ± 0.338 #□□ ]] Dosing group 11 46.31 ± 6.33 **&△□ ]] 2.244 ± 0.615 #&□ ]] Dosing group 12 48.39 ± 6.92 **△□ ]] 1.921 ± 0.457 ##&□ ]]

[0094] Note: compared with the sham operation group, * P<0.05; ** P<0.01; compared with the blank group, # P<0.05; ## P<0.01; compared with the model group, & P<0.05; && P<0.01; compared with the positive control group, △ P<0.05; △△P<0.01; compared with administration group 2, □ P<0.05; □□ P<0.01.

[0095] 2. Effects on lipid metabolism of rats

[0096] The test results of the lipid metabolism indexes of rats in each group are shown in Table 2. It can be seen that the traditional Chinese medicine composition prepared by each embodiment of the present application can significantly reduce the total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein levels of the diabetic nephropathy model rats; among them, administration group 8 (the traditional Chinese medicine composition prepared by Comparative Example 2), administration group 10 (the traditional Chinese medicine composition prepared by Comparative Example 4) and administration group 12 (the traditional Chinese medicine composition prepared by Comparative Example 6) have statistical differences (P<0.05 or P<0.01) in total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein content compared with administration group 2 (the traditional Chinese medicine composition prepared by Example 1), which shows that the use of the monarch drug Astragalus and the ministerial drug Red Peony, as well as the ministerial drug Red Peony and the auxiliary drug Saposhnikovia, has a greater impact on the lipid metabolism of diabetic nephropathy model rats.

[0097] Table 2 Lipid metabolism indexes of diabetic nephropathy rats

[0098]

[0099] Note: compared with the sham operation group, * P<0.05; ** P<0.01; compared with the blank group, # P<0.05; ## P<0.01; compared with the model group, & P<0.05; && P<0.01; compared with the positive control group, △ P<0.05; △△ P<0.01; compared with administration group 2, □ P<0.05; □□ P<0.01.

[0100] 3. Effects on liver function and protein synthesis of rats

[0101] The test results of the liver function related indexes and the serum protein content indexes of the rats in each group are shown in Table 3. It can be seen that the traditional Chinese medicine composition prepared by each embodiment of the present application can significantly reduce the alanine aminotransferase and aspartate aminotransferase levels of the diabetic nephropathy model rats, and the effect is slightly better than that of the positive control drug valsartan capsule, but there is no significant difference; compared with the administration group 2, the alanine aminotransferase and aspartate aminotransferase levels of the rats in the administration groups 7-12 are significantly improved (P<0.05 or P<0.01). It can be determined that the compatibility and dosage adjustment of each component in the traditional Chinese medicine composition of the present application achieve the recovery of liver function of the diabetic nephropathy model rats.

[0102] Table 3: Liver function indexes and protein synthesis results of diabetic nephropathy rats

[0103]

[0104] Note: compared with the sham operation group, * P<0.05; ** P<0.01; compared with the blank group, # P<0.05; ## P<0.01; compared with the model group, & P<0.05; && P<0.01; compared with the positive control group, △ P<0.05; △△ P<0.01; compared with the administration group 2, □ P<0.05; □□ P<0.01.

[0105] From the above, it can be concluded that the components in the traditional Chinese medicine composition of the present application are compatible with each other within a certain dosage range, which can improve the kidney function by reducing urinary protein excretion and increasing urinary creatinine excretion; at the same time, it can regulate lipid metabolism by reducing total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, and increasing total protein and albumin content; it can protect liver function by reducing alanine aminotransferase and aspartate aminotransferase; and it can also promote protein synthesis to a certain extent. It has a good therapeutic effect on type 2 diabetic nephropathy rats caused by high-fat high-sugar streptozotocin.

[0106] Experimental Example 2: Effect on sleep of mice

[0107] I. Experimental drugs and reagents:

[0108] The test drug is the traditional Chinese medicine composition prepared in Examples 1-4, which is dissolved and prepared into a concentration of 0.25 g crude drug / mL with citric acid buffer solution;

[0109] The sodium citrate buffer and sodium pentobarbital are purchased from the National Pharmaceutical Group Chemical Reagent Co., Ltd.

[0110] II. Experimental animals

[0111] KM mice 50, SPF, half male and female, body weight 18-22 grams, purchased from Kunming Medical University SPF Experimental Animal Center, license number: SCXK(Dian) K2015-0002; China Academy of Chinese Medical Sciences Xiyuan Hospital SPF animal room.

[0112] III. Experimental method

[0113] After the KM mice were adaptively fed for one week, they were randomly divided into 5 groups, 10 in each group, namely the blank group (normal saline), the drug administration groups 1-4 (the traditional Chinese medicine compositions prepared in Example 1, Example 4, Comparative Example 1, and Comparative Example 2).

[0114] The 48h acute sleep-promoting experiment was adopted, i.e. 3 times of gavage administration within 48h, 1h after the last gavage administration, the sleep latency and sleep duration of the mice were determined by using the minimum domain dose of pentobarbital sodium to induce sleep experiment (the dose of pentobarbital sodium injected into the abdominal cavity of each group of mice was 50mg / kg).

[0115] After one week, 3 times of gavage administration within 48h, 1h after the last gavage administration, the sleep occurrence rate of the mice was determined by using the maximum threshold dose of pentobarbital sodium (the dose of pentobarbital sodium injected into the abdominal cavity of each group of mice was 35mg / kg) to induce sleep occurrence experiment (the mice were inverted in the dorsal recumbency position, if the mice entered sleep, they could not immediately turn over the body position, otherwise they would turn over. Generally, if the time exceeds 30-60s without turning over, it is defined as the disappearance of the righting reflex, which means entering the sleep state).

[0116] IV. Experimental results

[0117] The sleep improvement results of the mice in each group above are shown in Table 4. It can be seen that the traditional Chinese medicine composition of the present application has a significant sleep improvement effect, especially the drug administration group 2 (the traditional Chinese medicine composition prepared in Example 4, which adds the traditional Chinese medicine composition of fried Suanzaoren and Shouwuteng); the drug administration groups 3 and 4 have extremely significant differences (P<0.01) in sleep latency and sleep duration compared with the drug administration group 1, and the sleep occurrence rate also has different degrees of reduction. It can be seen that the traditional Chinese medicine composition of the present application also has a significant effect on improving sleep.

[0118] Table 4 Results of the influence on the sleep of mice

[0119]

[0120] Note: compared with the blank group, * P<0.05; **P<0.01; compared with administration group 1, # P<0.05; ## P<0.01.

[0121] Experimental Example 3: Clinical experiment

[0122] I. 60 DKD subjects (patients aged 44-74 years old admitted to the Xiyuan Hospital of China Academy of Chinese Medical Sciences from July 2020 to September 2023) meeting the diagnostic criteria of DKD were randomly divided into a test group (30 cases) and a control group (30 cases). Both groups received conventional western medicine treatment, including reasonable diet, appropriate exercise, blood sugar control, blood pressure control, and blood lipid control.

[0123] On the basis of conventional western medicine therapy, the test group took the traditional Chinese medicine composition (the traditional Chinese medicine composition prepared in Example 1, which was granulated by a dry granulation process. Specifically, the extract prepared in Example 1 was dried to a water content of less than 2 wt%, mixed with dextrin at a mass ratio of 1:1, and granulated to obtain a granule). The control group took Qizhu granules (a traditional Chinese medicine composition prepared in Comparative Example 1, which was granulated in the same way). Both the test group and the control group took one bag (10 g per bag) of medicine three times a day, and the treatment course was 3 months. The changes in urinary microalbumin and urinary microalbumin creatinine ratio (ACR) of the subjects in the two groups before and after the intervention were compared.

[0124] II. Diagnostic criteria for DKD

[0125] 1. Western medicine diagnostic criteria

[0126] Refer to the diagnostic criteria formulated in the 2019 “Clinical Guidelines for Prevention and Treatment of Diabetic Kidney Disease in China”:

[0127] ① There is a clear history of diabetes, and the course of disease is usually more than 5 years;

[0128] ② Repeat urinary microalbumin creatinine ratio (ACR) test within 3-6 months, and ACR is >30 mg / g in 2 of 3 consecutive tests; or urinary albumin excretion rate (UAER) is >20 μg / min; and / or estimated glomerular filtration rate (eGFR) is <60 mL·min -1 ·1.73m -2 ; the duration is more than 3 months;

[0129] ③ And can rule out other causes of increased urinary protein caused by kidney disease.

[0130] 2. Diagnostic criteria for TCM syndromes

[0131] Refer to the diagnostic criteria formulated in the 2011 “Guidelines for Prevention and Treatment of Diabetic Nephropathy in Traditional Chinese Medicine” as follows:

[0132] Main symptoms: fatigue, shortness of breath, self-harm, and night sweats.

[0133] Sub-symptoms: five heart heat, irritability, insomnia, nocturia, polydipsia.

[0134] Concurrent symptoms: numbness or pain in limbs, fixed pain, skin and nails.

[0135] Tongue and pulse: pale red or purple tongue or ecchymosis, little or flower peeling, sublingual vessels purple or varicosity, pulse soft and weak or sunken and astringent.

[0136] At least 2 main symptoms, 1 sub-symptom, 1 concurrent symptom, combined with tongue and pulse can be diagnosed.

[0137] III. Clinical test results

[0138] The ratio of urine microalbumin and creatinine (ACR) reflects early proteinuria, which is one of the important indicators for screening early chronic kidney disease and diabetes. The ACR of each group of patients before and after treatment was detected, and the results are shown in Table 5.

[0139] Table 5 Comparison of ACR (mg / g) of two groups of patients before and after treatment / M (Q25, Q75)

[0140] Group Control group Test group Before treatment 88.21(50.85,137.43) 75.69(45.90,205.91) After treatment 121.78(21.54,187.67) 43.06(22.33,123.24) P value 0.432 0.007

[0141] As can be seen from Table 5, the ACR result after treatment of the traditional Chinese medicine composition of the application is significantly lower than that before treatment, with statistical difference (P<0.01); while the control group uses the traditional Chinese medicine composition of Comparative Example 1 for treatment, the ACR result of the patients after treatment is increased instead; thus, through the optimization of the compatibility relationship and the amount of each component in the traditional Chinese medicine composition, the application realizes the control of early proteinuria, and has good therapeutic effect on chronic kidney disease and diabetes.

[0142] To further compare the treatment of diabetic nephropathy patients by the traditional Chinese medicine compositions of Example 1 and Comparative Example 1, the urine microalbumin quantification and urine microalbumin creatinine ratio before and after taking the prescription were used as standards, SPSS11.0 statistical software was used for analysis and processing, and the results were statistically significant, as shown in Table 6.

[0143] Table 6 Treatment effect of two groups of diabetic nephropathy patients

[0144]

[0145] Note: a, urine microalbumin quantification or urine microalbumin creatinine ratio decreased after intervention (treatment effect is effective);

[0146] b, urine microalbumin quantification or urine microalbumin creatinine ratio increased after intervention (treatment effect is ineffective).

[0147] As shown in Table 6, the Chinese medicine composition prepared by the present application has a treatment effective rate of more than 80% for diabetic nephropathy patients, and the effect is remarkable.

[0148] Finally, it should be noted that the above content is only used to illustrate the technical solutions of the present application, and is not a limitation on the protection scope of the present application. Simple modifications or equivalent replacements of the technical solutions of the present application made by those skilled in the art do not deviate from the essence and scope of the technical solutions of the present application.

Claims

1. A traditional Chinese medicine composition for diabetic nephropathy, characterized in that, The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 20-50 parts of Huangqi, 10-15 parts of Chishao, 8-12 parts of Fangfeng, 25-35 parts of Mufu Baishu, 25-35 parts of Baomaren, 10-20 parts of Jinyingzi, and 10-20 parts of Jienuzizi.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 25-35 parts of Huangqi, 11-13 parts of Chishao, 9-11 parts of Fangfeng, 28-32 parts of Mufu Baishu, 28-32 parts of Baomaren, 12-18 parts of Jinyingzi, and 12-18 parts of Jienuzizi.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 30 parts of Huangqi, 12 parts of Chishao, 10 parts of Fangfeng, 30 parts of Mufu Baishu, 30 parts of Baomaren, 15 parts of Jinyingzi, and 15 parts of Jienuzizi.

4. A traditional Chinese medicine composition for diabetic nephropathy, characterized in that, The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 30 parts of Huangqi, 12 parts of Chishao, 10 parts of Fangfeng, 30 parts of Mufu Baishu, 30 parts of Baomaren, 15 parts of Jinyingzi, 15 parts of Jienuzizi, 30 parts of Chousuanzaoren, and 30 parts of Shouwuteng.

5. The preparation method of the traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The method comprises the following steps: (1) grinding all the raw materials and sieving, for standby use; (2) adding the raw materials Huangqi, Fangfeng, Mufu Baishu, Baomaren, and Jienuzizi into an ethanol solution, and performing alcohol extraction, and filtering to obtain filtrate A; (3) adding the raw materials Chishao and Jinyingzi into water, and performing water extraction, and after the end, adding ethanol for precipitation and filtering to obtain filtrate B; (4) combining the filtrate A and the filtrate B, and concentrating, to obtain the traditional Chinese medicine composition.

6. The production method according to claim 5, characterized by, In step (2), the concentration of the ethanol solution is 50-80 vol%; the alcohol extraction is performed for 1-4 times, and the extraction time is 1-2 h each time; and the solid-liquid ratio of the raw materials to the ethanol solution is 1 g:5-10 mL.

7. The preparation method according to claim 5, characterized in that, In step (3), the water extraction is performed for 1-4 times, and the extraction time is 1-2 h each time; and the solid-liquid ratio of the raw materials to water is 1 g:10-20 mL.

8. Use of the traditional Chinese medicine composition of any one of claims 1-4 or the traditional Chinese medicine composition prepared by the preparation method of any one of claims 5-7 in the preparation of a medicine for preventing and / or treating diabetic nephropathy.

9. A traditional Chinese medicine preparation, characterized in that, The traditional Chinese medicine composition of any one of claims 1-4 or the traditional Chinese medicine composition prepared by the preparation method of any one of claims 5-7; and the dosage form of the traditional Chinese medicine preparation is any one of a tablet, a granule, a capsule, a decoction, and a plaster.

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