Traditional Chinese medicine composition for reducing blood sugar and blood fat

Abstract

The invention provides a traditional Chinese medicine composition for reducing blood sugar and blood fat. The traditional Chinese medicine composition is prepared from the following traditional Chinese medicinal materials in specific parts by weight: astragalus membranaceus, semen cuscutae, abelmoschus manihot, schisandra chinensis, fructus rosae laevigatae, gordon euryale seed, lumbricus, stiff silkworm, burdock, gallnut, salvia miltiorrhiza, oldenlandia diffusa and the like. Furthermore, the invention provides a preparation and a preparation method of the compound and application of the compound in medicines for preventing or treating hyperlipidemia, diabetes or diabetic nephropathy.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine compositions, and in particular to a traditional Chinese medicine composition for treating diabetic nephropathy, its preparation method, and its application. Background Technology

[0002] Diabetes mellitus (DM) is a global chronic disease with an increasing incidence, and the kidneys are the most important target for microvascular damage in diabetes. Most people with type 2 diabetes and type 1 diabetes will develop kidney disease due to their own disease and / or other comorbidities, including hypertension, dyslipidemia, obesity, intrarenal vascular disease, renal ischemia, or age-related loss of nephrons.

[0003] Diabetic nephropathy (DKD), formerly known as diabetic nephropathy (DN), is one of the most common microvascular complications of diabetes and a leading cause of end-stage renal disease worldwide. Clinically, DKD is characterized by proteinuria, elevated creatinine, and abnormal glomerular filtration rate, eventually progressing to end-stage renal disease. Its main pathological features include podocyte loss, foot process disappearance, glomerular hypertrophy and sclerosis, glomerular basement membrane (GBM) thickening, mesangial matrix expansion, interstitial fibrosis, and tubular atrophy, ultimately leading to irreversible structural damage to the kidneys.

[0004] With the rising prevalence of diabetes, the incidence of diabetic kidney disease (DKD) will also rise rapidly. The cardiovascular morbidity and mortality rates of DKD patients are dozens of times higher than those of diabetic patients without kidney disease. Moreover, DKD remains one of the leading causes of end-stage renal disease (ESRD). The prevention and management of diabetic nephropathy and its associated cardiovascular morbidity and mortality is a huge global challenge and a heavy social and economic burden.

[0005] The pathogenesis of kidney disease (DKD) is multifactorial, involving genetic susceptibility, glucose and lipid metabolism disorders, oxidative stress, inflammation, fibrosis, and apoptosis. Metabolic (hyperglycemia, dyslipidemia) and hemodynamic (glomerular hypertension) disturbances are considered the main driving factors of DKD. Glucose and lipid metabolism imbalances not only directly increase the burden on the kidneys but also induce lipotoxicity and mitochondrial dysfunction; hemodynamic abnormalities lead to glomerular hyperfiltration and microcirculatory damage; the continuous generation of excessive ROS triggers oxidative stress, which in turn activates multiple inflammatory and apoptotic signaling pathways; the increase of inflammatory factors and fibrotic factors promotes ECM deposition and renal tissue structural damage; and the imbalance of apoptosis further aggravates damage to the glomeruli and renal tubules.

[0006] Currently, there is no specific treatment for diabetic nephropathy. Western medicine primarily focuses on lowering blood sugar, blood pressure, and blood lipids, using medications such as RAAS inhibitors, SGLT2 inhibitors, and GLP-1 receptor agonists. While these can slow disease progression to some extent, they have limitations in preventing the continued deterioration of kidney function and the development of end-stage renal disease. Traditional Chinese medicine treatments for proteinuria lack specificity, and their efficacy is not significant, with a relatively slow onset of action.

[0007] Therefore, there is an urgent need to further explore new intervention strategies that are more comprehensive, multi-targeted, and synergistic, in order to stop the progression of DKD by targeting various factors that affect the disease process. Summary of the Invention

[0008] To address one of the aforementioned technical problems in the prior art, the present invention provides a traditional Chinese medicine composition for treating diabetic nephropathy. Furthermore, the present invention also provides a preparation of this traditional Chinese medicine composition, particularly a decoction, and the application of this traditional Chinese medicine composition.

[0009] According to one aspect of the present invention, the traditional Chinese medicine composition for treating diabetic nephropathy provided by the present invention is made from the following traditional Chinese medicinal materials in parts by weight: Astragalus membranaceus 10-20 parts, Cuscuta chinensis 5-18 parts, Hibiscus syriacus 5-18 parts, Schisandra chinensis 1-15 parts, Rosa laevigata 10-20 parts, Euryale ferox 10-20 parts, Pheretima aspergillum 5-18 parts, Bombyx mori 5-18 parts, Arctium lappa 5-18 parts, Galla chinensis 5-18 parts, Salvia miltiorrhiza 10-20 parts, and Hedyotis diffusa 20-40 parts.

[0010] According to one embodiment of the present invention, the traditional Chinese medicine composition is made from the following traditional Chinese medicinal materials in parts by weight: 15 parts Astragalus membranaceus, 10 parts Cuscuta chinensis, 10 parts Hibiscus syriacus, 6 parts Schisandra chinensis, 15 parts Rosa laevigata, 15 parts Euryale ferox, 10 parts Pheretima aspergillum, 10 parts Bombyx mori, 10 parts Arctium lappa, 10 parts Galla chinensis, 15 parts Salvia miltiorrhiza, and 30 parts Hedyotis diffusa.

[0011] According to one preferred embodiment of the present invention, a traditional Chinese medicine composition is made from the following traditional Chinese medicinal materials in parts by weight: 12 parts Astragalus membranaceus, 8 parts Cuscuta chinensis, 14 parts Hibiscus syriacus, 9 parts Schisandra chinensis, 12 parts Rosa laevigata, 10 parts Euryale ferox, 13 parts Pheretima aspergillum, 12 parts Bombyx mori, 15 parts Arctium lappa, 6 parts Galla chinensis, 20 parts Salvia miltiorrhiza, and 34 parts Hedyotis diffusa.

[0012] According to one preferred embodiment of the present invention, a traditional Chinese medicine composition is made from the following traditional Chinese medicinal materials in parts by weight: Astragalus membranaceus 10 parts, Cuscuta chinensis 15 parts, Hibiscus rosa-sinensis 6 parts, Schisandra chinensis 11 parts, Rosa laevigata 20 parts, Euryale ferox 20 parts, Pheretima aspergillum 5 parts, Bombyx mori 5 parts, Arctium lappa 5 parts, Galla chinensis 15 parts, Salvia miltiorrhiza 10 parts, and Hedyotis diffusa 25 parts.

[0013] According to one preferred embodiment of the present invention, a traditional Chinese medicine composition is made from the following traditional Chinese medicinal materials in parts by weight: Astragalus membranaceus 20 parts, Cuscuta chinensis 5 parts, Hibiscus syriacus 15 parts, Schisandra chinensis 3 parts, Rosa laevigata 10 parts, Euryale ferox 10 parts, Pheretima aspergillum 15 parts, Bombyx mori 15 parts, Arctium lappa 12 parts, Galla chinensis 8 parts, Salvia miltiorrhiza 18 parts, and Hedyotis diffusa 32 parts.

[0014] The traditional Chinese medicine composition provided by this invention includes:

[0015] Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bqe., belonging to the Fabaceae family, is the dried root of the plant. It is harvested in spring and autumn, with the fibrous roots and root heads removed before being sun-dried. It is mainly distributed in Gansu, Inner Mongolia, Shanxi, and Northeast China. It has a sweet taste and slightly warm properties. It enters the Lung and Spleen meridians. Its main functions are to tonify Qi and raise Yang, consolidate the exterior and stop sweating, promote diuresis and reduce swelling, generate fluids and nourish blood, promote circulation and relieve pain, promote pus drainage, and astringe sores and promote tissue regeneration. The *Tangye Bencao* (Compendium of Materia Medica) records that Astragalus membranaceus (Huangqi) is a remedy for the "Foot Shaoyin and Mingmen" meridians, and also states that it "powerfully tonifies the kidneys." Furthermore, Astragalus membranaceus can relieve deficiency heat caused by insufficient Qi and Yin. The *Shennong Bencao Jing Shu* (Commentary on Shennong's Classic of Materia Medica) states that Astragalus membranaceus "benefits Qi and benefits Yin, as Yang generates Yin." Astragalus membranaceus benefits Qi and assists Yang, with Yin and Yang mutually supporting each other; as Yang grows, Yin follows, and as Yin is generated, the heat is extinguished, and the heat subsides. The main active components of Astragalus membranaceus are saponins, polysaccharides, and flavonoids, which have the effects of enhancing immunity, anti-fatigue, and anti-tumor properties. It also has a certain protective effect on organs such as the heart, lungs, brain, gastrointestinal tract, liver, kidneys, and nervous system.

[0016] Cuscuta seed, the dried, mature seed of *Cuscuta australis* R.Br. or *Cuscutachinensis* Lam., both belonging to the Convolvulaceae family, is harvested in autumn when the fruit is ripe. The plants are dried, the seeds are threshed, and impurities are removed. It has a pungent and sweet taste and is neutral in nature. It enters the liver, kidney, and spleen meridians. Its main functions are: tonifying the liver and kidneys, strengthening essence and reducing urination, calming the fetus, improving eyesight, and stopping diarrhea; externally, it is used to dispel wind and remove blemishes. Cuscuta seed mainly contains flavonoids, lignans, polysaccharides, and other chemical components. It has protective effects on the reproductive system, immune regulation, and anti-tumor effects.

[0017] Yellow hibiscus flower is the dried corolla of *Abelmoschus manihot* (L.) Medic., a plant in the Malvaceae family. It is harvested during the summer and autumn when the flowers bloom and dried promptly. It has a sweet taste and cold nature, and enters the kidney and bladder meridians. Its main functions are clearing heat and dampness, reducing swelling and detoxifying. The main active ingredients in yellow hibiscus flower are flavonoids, and it also contains reducing sugars, organic acids, tannins, and long-chain hydrocarbons. It has anti-inflammatory, antipyretic, analgesic, hypoglycemic, protective effects against cerebral and myocardial ischemia, liver damage, improved kidney function, and repair of oral mucosa effects.

[0018] Schisandra chinensis, the dried, ripe fruit of the Magnoliaceae plant Schisandra chinensis (Turcz.) Bai., is commonly known as "Northern Schisandra." It is harvested in autumn when the fruit is ripe, sun-dried, or steamed and then sun-dried, removing the fruit stalks and impurities. It has a sour and sweet taste and is warm in nature. It enters the lung, heart, and kidney meridians. Its main functions are astringent and consolidating, replenishing qi and promoting body fluids, tonifying the kidneys and calming the mind. The chemical components of Schisandra chinensis mainly include lignans, volatile oils, organic acids, terpenes, flavonoids, polysaccharides, and inorganic elements. Lignans are the main components and are the basic substances for various pharmacological activities. Schisandra chinensis has good antioxidant, antitumor, hepatoprotective, and anti-inflammatory pharmacological effects.

[0019] Rosa laevigata fruit, also known as golden cherry fruit, is the dried, ripe fruit of the Rosa laevigata Michx. plant, belonging to the Rosaceae family. It is harvested in October and November when the fruit turns red, dried, and the thorns removed. It is mainly produced in Sichuan, Guangdong, and Yunnan provinces of my country. It has a sour, sweet, and astringent taste, and is neutral in nature. It enters the kidney, bladder, and large intestine meridians. Its main uses include: strengthening essence and reducing urination, stopping uterine bleeding and leukorrhea, and astringing the intestines and stopping diarrhea. The chemical components of the Rosa laevigata plant mainly include flavonoids, triterpenoids, tannins, phenylpropanoids, steroids, and polysaccharides. Among these, flavonoids and triterpenoids mainly exert anti-inflammatory, antibacterial, and anticancer effects, while tannins are the main material basis for its astringent effect.

[0020] Euryale ferox Salisb., a plant in the Nymphaeaceae family, is the dried, mature seed kernel. Mature fruits are harvested in late autumn or early winter. The pericarp is removed, the seeds are extracted, washed, and the hard outer seed coat is removed before drying. It has a sweet and astringent taste and is neutral in nature. It enters the spleen and kidney meridians. Its main functions are: tonifying the kidneys and securing essence, strengthening the spleen and stopping diarrhea, and eliminating dampness and stopping leukorrhea. The main medicinal components of Euryale ferox are polysaccharides, polyphenols, tocopherols, sesquineans, cyclic dipeptides, cerebrosides, flavonoids, and minerals. It has antioxidant and free radical scavenging functions, lowers blood sugar, improves myocardial ischemia, reduces proteinuria, inhibits bacteria, and prevents gastric mucosal damage.

[0021] Earthworm, also known as Pheretima aspergillum (E. Perrier), commonly known as Pheretima ventricula Chen, Pheretima guillelmi (Michaelsen), or Pheretima pectinifera Michaelsen, are all species belonging to the family Pheretidae. The former is commonly called "Guangdong earthworm," while the latter three are commonly called "Shanghai earthworm." Guangdong earthworms are captured from spring to autumn, while Shanghai earthworms are captured in summer. The abdomen is promptly dissected, the internal organs and mud removed, washed, and then sun-dried or dried at low temperature. It has a salty taste and cold properties. It enters the liver, spleen, and bladder meridians. Its main functions are clearing heat and calming the nerves, unblocking the meridians, relieving asthma, and promoting diuresis. It contains various active ingredients such as proteins, polypeptides, and amino acids, and has anticoagulant, anti-fibrotic, blood pressure-lowering, immune-regulating, anti-tumor, blood sugar-lowering, and wound-healing effects.

[0022] Silkworm larvae (Bombyx mori Linnaeus) are the dried bodies of 4th-5th instar larvae that have died from infection (or artificial inoculation) with Beauveria bassiana (Bal.,) Vuilant. Production is mainly carried out in spring and autumn, using dried silkworms that have died from Beauveria bassiana infection. They have a salty and pungent taste, and are neutral in nature. They enter the liver, lung, and stomach meridians. Their main functions are to relieve wind and spasms, dispel wind and relieve pain, and resolve phlegm and dissipate nodules. Silkworm larvae possess various pharmacological effects, including anticonvulsant, anticoagulant, antithrombotic, anticancer, hypnotic, and hypoglycemic effects. Their main components include proteins, polypeptides, amino acids, nucleosides, organic acids, steroids, flavonoids, polysaccharides, and trace elements.

[0023] Burdock seed is the dried, mature fruit of *Arctium lappa* L., a plant in the Asteraceae family. The inflorescences are harvested in autumn when the fruit is ripe, dried in the sun, the fruits are threshed, impurities are removed, and then dried again. It has a pungent and bitter taste and is cold in nature. It enters the lung and stomach meridians. Its main functions are to disperse wind-heat, promote lung function and relieve rashes, detoxify and soothe the throat. The main components include lignans, volatile oils, fatty oils, and terpenes, among which lignans are the main active components, represented by arctiin and arctigenin. Burdock seed has antibacterial, anti-inflammatory, antiviral, antitumor, and hypoglycemic effects.

[0024] Gallnut, or Rhus chinensis Mil., Rhus potaninii Maxim., or Rhus punjabensis Stew, var. sinica (Diels) Rehd. et Wils., are insect galls on the leaves of plants in the Anacardiaceae family. They are primarily formed by the gall aphid Melapis chinensis (Bell) Baker. They are mainly produced in Sichuan and Guizhou provinces. Harvested in autumn, the gallnuts are briefly boiled or steamed until the surface turns gray to kill the aphids, then removed and dried. Based on their shape, they are divided into "belly gallnuts" and "horn gallnuts." They have a sour, astringent, and cold nature. They enter the lung, large intestine, and kidney meridians. Their main functions include astringing the lungs and reducing heat, astringing the intestines and stopping diarrhea, reducing sweating, stopping bleeding, and astringing sores. The main components include tannins and gallic acid. They possess antibacterial, anti-inflammatory, antioxidant, and anti-tumor functions.

[0025] Danshen (Salvia miltiorrhiza) is the dried root and rhizome of the plant *Salvia miltiorrhiza* Bge., belonging to the Lamiaceae family. It is harvested in spring and autumn, cleaned of dirt, and dried. It is mainly produced in Shandong, Hebei, and Sichuan provinces. It has a bitter taste and is slightly cold in nature. It enters the heart and liver meridians. Its main functions are: promoting blood circulation and removing blood stasis, regulating menstruation and relieving pain, clearing the heart and relieving irritability, cooling the blood and reducing swelling. Its main components include tanshinone II-A, cryptotanshinone, tanshinone I, and dihydrotanshinone I. Water-soluble tanshinone derivatives mainly function as lipid regulators, cell protectants, antioxidants, anticoagulants, and antithrombotic agents; lipid-soluble tanshinone derivatives mainly function as antibacterial agents, anti-inflammatory agents, and agents that improve blood circulation.

[0026] Hedyotis diffusa, also known as white flower snake tongue grass, is the whole herb of *Hedyotis diffusa* Willd. [Oldenlandia diffusa (Willd.) Roxb.], a plant belonging to the Rubiaceae family and the *Hedyotis* genus. It is harvested in summer and autumn, washed, and used fresh or dried. It enters the stomach, large intestine, and small intestine meridians. It has a sweet and bland taste and is cool in nature. Its main chemical components include flavonoids, anthraquinones, terpenes, polysaccharides, and other compounds. It possesses various pharmacological activities, including antioxidant, anti-inflammatory, and anticancer effects.

[0027] Based on in-depth research into the material basis of the traditional Chinese medicine composition provided by this invention, it includes one or more of the following components: sugars and their derivatives, flavonoids, amino acids and their derivatives, alkaloids, lignans, fatty acids and their derivatives, phenolic acids, phenylpropanoids, coumarins, terpenoids, isoflavones, nucleosides, amides, benzene polyphenols, and choline compounds.

[0028] Further, according to the present invention, the traditional Chinese medicine composition comprises one or more of the following components: tacrolimus, allose, D-glucopyranose, L-sorbose, glucose monohydrate, 1,3-dihydroxyacetone, DL-glyceraldehyde crystals, gluconic acid, erythritol lactone, protopanaxadione 4'-glucoside, gossypol-8-O-glucuronide, isoquercitrin, hesperidin 7-O-glucoside, epigallocatechin, cyanidin, (+)-epigallocatechin, proline, betaine, DL-tryptophan, L-tryptophan, D-pyroglutamic acid, L-pyroglutamic acid, 2-piperidinone, flavonolactam, 1H-imidazol-1-acetic acid, (-)- Cabernet, 2-amino-1-phenylethanol, norcolchicine, schisandrin, schisandrol A, arctigenin, pinoresinin 4-O-glucoside, (R)-2-aminoheptane, malic acid, isocitrate, lactic acid, azelaic acid, salvianolic acid B, isosanthanolic acid B, gallic acid, 5-galloshikimic acid, pentagalloglucoside, rosmarinic acid, cryptochlorogenic acid, p-hydroxycinnamic acid, scopolamine, methylfraxin, styracin, chrysogenin D, deoxyrhonic acid, dicotyl oleate BO-β-D-glucopyranoside, 5-O-methylgenistein, daidzein, adenosine, adenosine, oleamide, isovaleramide, phloroglucinol, pyroglucinol, and choline, etc.

[0029] According to another aspect of the present invention, a formulation of the traditional Chinese medicine composition is also provided, which is composed of the above-described traditional Chinese medicine composition and pharmaceutically acceptable excipients.

[0030] According to the present invention, the formulation includes one or more of the following: liquid formulation, solid formulation, and spray.

[0031] In some embodiments, the traditional Chinese medicine composition preparation includes one or more of the following: decoction, extract, pill, powder, granule and capsule.

[0032] In some specific embodiments, the preparation includes an aqueous decoction of the traditional Chinese medicine composition, a traditional Chinese medicine extract obtained by decocting and concentrating the decoction, granules obtained by spray drying the traditional Chinese medicine extract with excipients, pills obtained by adding excipients to the traditional Chinese medicine extract, or an aqueous extract obtained by heating, reflux extraction, filtration and concentration.

[0033] In some specific embodiments, the excipients include one or more of dextrin, microcrystalline cellulose, or hydroxypropyl methylcellulose.

[0034] According to another aspect of the present invention, a method for preventing or treating diabetic nephropathy using the traditional Chinese medicine composition and / or the preparation is provided, the method comprising administering to a subject a pharmaceutically effective amount of the traditional Chinese medicine composition, the preparation, or the pharmaceutical composition.

[0035] According to another aspect of the present invention, the use of the traditional Chinese medicine composition, the preparation and / or the composition prepared by the method is provided in the prevention or treatment of hyperlipidemia, diabetes or diabetic nephropathy.

[0036] In some implementations, the drug can be used for any one or more of the following:

[0037] 1) Reduce weight;

[0038] 2) Maintain lipid metabolism balance

[0039] 3) Maintain blood sugar balance;

[0040] 4) Protect or improve kidney and / or liver function;

[0041] 5) Delay the onset and progression of diabetic nephropathy.

[0042] In some implementations, maintaining lipid metabolism balance includes improving lipid metabolism disorders or abnormalities, specifically including one or more of the following: significantly improving abnormally elevated triglyceride levels, significantly improving abnormally elevated total cholesterol levels, significantly improving high-density lipoprotein cholesterol levels, and significantly improving abnormally elevated low-density lipoprotein cholesterol levels.

[0043] In some implementations, maintaining blood glucose balance includes improving glucose metabolism disorders or abnormalities, specifically including improving abnormally high fasting blood glucose levels.

[0044] In some implementations, the protection or improvement of renal function includes one or more of the following: improving abnormally decreased water intake, maintaining stable urine output, improving abnormally elevated urine protein levels, reducing renal inflammatory lesions, improving renal collagen deposition and fibrosis, inhibiting renal cell apoptosis or improving abnormally elevated renal index, reducing glycogen deposition in renal tubules, improving pathological changes in renal tubular epithelial cells, improving abnormally thickened basement membrane (TBM) thickness, improving renal fibrosis, improving increased abnormal renal cell apoptosis, reducing glomerular and tubular lesions, reducing inflammatory cell infiltration, improving pathological changes in renal foot processes and glomerular basement membranes, reducing abnormal deposition of basement membrane components such as type IV collagen and fibronectin, and protecting the glomerular filtration barrier structure.

[0045] In some implementations, the urinary protein includes urinary albumin.

[0046] In some implementations, the improvement of urinary protein includes one or more of the following: significantly improving abnormally high urinary protein levels, significantly improving abnormally high urinary albumin excretion rate (UAER), improving and reducing abnormally high urinary protein / creatinine ratio, significantly improving abnormally high serum creatinine (Scr), reducing blood urea nitrogen (BUN), and reducing blood uric acid (SUA).

[0047] In some implementations, the protection or improvement of liver function includes the prevention and / or treatment of liver damage caused by diabetic nephropathy.

[0048] In some implementations, the protection or improvement of liver function includes one or more of the following: improving abnormally elevated alanine aminotransferase (ALT), improving pathological structural changes in the liver, and reducing the subject's liver index.

[0049] In some implementations, the improvement of liver pathological structural changes includes one or more of the following: effectively reducing the number of liver fat droplets and significantly improving liver steatosis, etc.

[0050] The traditional Chinese medicine composition provided by this invention has a reasonable formulation, is suitable for various dosage forms, and is suitable for large-scale production in an industrial environment. The composition is safe and effective, significantly improving glucose and lipid metabolism, liver and kidney function, and proteinuria, with some improvements exceeding those of existing technologies and without showing significant liver and kidney damage, demonstrating biocompatibility. Attached Figure Description

[0051] Figure 1 The TIC peak diagram of the traditional Chinese medicine composition in positive ion mode is shown.

[0052] Figure 2 The TIC peak diagram of the negative ion mode of the traditional Chinese medicine composition is shown.

[0053] Figure 3 The effects of each drug group on mouse body weight are shown.

[0054] Figure 4 The effects of each drug group on the kidney weight of mice were shown.

[0055] Figure 5 The effects of each drug group on the kidney index in mice are shown.

[0056] Figure 6 The effects of each drug group on liver weight in mice are shown.

[0057] Figure 7 The effects of each drug group on the liver index in mice are shown.

[0058] Figure 8 The effects of each drug group on fasting blood glucose in mice were shown.

[0059] Figure 9 The effects of each drug group on 24-hour urine output in mice were shown.

[0060] Figure 10 The effects of each drug group on 24-hour urinary protein in mice were shown.

[0061] Figure 11The effects of each drug group on the urinary albumin excretion rate in mice were shown.

[0062] Figure 12 The effects of each drug group on the urinary microalbumin / creatinine ratio in mice were shown.

[0063] Figure 13 The effects of each drug group on serum creatinine in mice were shown.

[0064] Figure 14 The effects of each drug group on blood urea nitrogen in mice are shown.

[0065] Figure 15 The effects of each drug group on serum uric acid in mice were shown.

[0066] Figure 16 The effects of each drug group on triglycerides in mice were shown.

[0067] Figure 17 The effects of each drug group on total cholesterol in mice were shown.

[0068] Figure 18 The effects of each drug group on high-density lipoprotein cholesterol in mice were shown.

[0069] Figure 19 The effects of each drug group on low-density lipoprotein cholesterol in mice were shown.

[0070] Figure 20 The effects of each drug group on alanine aminotransferase in mice were shown.

[0071] Figure 21 The effects of each drug group on mouse aspartate aminotransferase were shown.

[0072] Figure 22 The effects of each drug group on mouse serum albumin were shown.

[0073] Figure 23 The image shows an HE-stained (200×) section of a mouse liver.

[0074] Figure 24 The image shows an observation of a mouse kidney section stained with HE (200×).

[0075] Figure 25 The image shows a PAS-stained (400×) section of a mouse kidney.

[0076] Figure 26 The image shows a Masson-stained (200×) section of a mouse kidney.

[0077] Figure 27 The image shows a Masson-stained (200×) section of a mouse kidney.

[0078] Figure 28 The image shows an electron microscope (15000×) section of a mouse kidney. Detailed Implementation

[0079] The traditional Chinese medicine provided by this invention is rich in various components, including sugars and their derivatives, flavonoids, lignans, phenolic acids, alkaloids, fatty acids, terpenes, phenylpropanoids, and coumarins. It exhibits typical characteristics of a traditional Chinese medicine compound formula: "multi-component, multi-target, multi-functional, and multi-level." Diabetic nephropathy is a complex disease involving multiple factors such as metabolic disorders, inflammation activation, oxidative stress, fibrosis, and cell damage. Its complex pathological mechanisms perfectly align with the intervention approach of traditional Chinese medicine compound formulas, which utilize multi-target and multi-pathway synergistic effects.

[0080] Results of mouse animal model experiments showed that the traditional Chinese medicine (TCM) composition significantly reduced fasting blood glucose and significantly improved TC, LDL-C, and HDL-C levels, thus regulating glucose and lipid metabolism. It also improved diet, water intake, and renal function. The TCM composition significantly improved 24-hour urinary protein, UAER, and ACR. Specifically, the low-dose group of the TCM composition was more effective than losartan potassium in reducing Scr and SUA, while losartan potassium was more effective than dapagliflozin. The medium- and high-dose groups of the TCM composition were comparable to the positive control drug in reducing 24-hour urinary protein. The high-dose group showed superior efficacy in reducing UAER (high-dose > losartan potassium > dapagliflozin). In reducing ACR, the three dose groups of the TCM composition were comparable to losartan potassium, and may be slightly better than dapagliflozin. During the drug intervention period, mouse body weight did not change significantly but showed a decreasing trend. Dapagliflozin is an SGLT2 inhibitor, and studies have shown that it can alleviate metabolic disorders caused by hyperglycemia, reduce proteinuria, protect renal function, and slow the progression of DKD. Losartan potassium is an ARB class antihypertensive drug and is currently recommended as an effective treatment strategy to slow the progression of kidney disease. Dapagliflozin and losartan potassium are both representative Western medicines recommended in current clinical guidelines for the treatment of kidney disease (DKD).

[0081] While proteinuria is not the sole diagnostic criterion for diabetic kidney disease (DKD), it is a significant risk factor for renal prognosis. Proteinuria in diabetic patients is associated with cardiovascular disease, CKD progression, and mortality risk, suggesting that the traditional Chinese medicine (TCM) composition has the potential to delay DKD progression by reducing proteinuria. Furthermore, high doses of the TCM composition significantly reduced ALT, while low and medium doses showed comparable but not significant ALT reductions compared to the positive control drug. AST showed no significant changes in the normal group, model group, and all treated groups; however, serum albumin levels may have increased in some treated groups. These results indicate that the TCM composition has no significant hepatotoxic or nephrotoxic side effects.

[0082] Albuminuria not only reflects damage to the glomerular filtration barrier but is also influenced by glomerular hyperfiltration and tubular reabsorption. The presence of albuminuria suggests glomerular and tubular pathologies. At the glomerular level, hyperfiltration, endothelial dysfunction, basement membrane thickening, podocyte foot process fusion or detachment, glomerular sclerosis, and arteriolar hyalinization can all lead to proteinuria. Studies have shown that inflammation is also associated with changes in glomerular endothelial permeability, mesangial cell expansion, elevated fibronectin levels, and glomerular basement membrane thickening. In the tubules, tubular inflammation, atrophy, and reduced reabsorption of amino acids and proteins in the proximal tubules play a crucial role in the progression of DKD exacerbated by proteinuria. Renal fibrosis is a significant and highly relevant topic in nephrology; it is a hallmark and common outcome of various progressive CKD diseases and the best predictor of CKD progression. Combined observations using HE staining, PAS staining, Masson staining, and electron microscopy revealed that the traditional Chinese medicine composition reduced inflammatory cell infiltration in the tissue, improved pathological structural changes in the glomeruli and renal tubules (including improved morphology of renal tubular epithelial cells, reduced thickening of GBM and TBM, and reduced foot process fusion), and reduced ECM deposition and tissue fibrosis.

[0083] Sustained hyperglycemia leads to excessive glycogen accumulation in the kidneys, thereby impairing kidney function, a common manifestation of diabetic kidney disease (DKD). Observation of PAS staining results in the kidneys showed that the traditional Chinese medicine composition could reduce glycogen deposition in the renal tubules, with a better effect than losartan potassium. Experiment 2 suggested that the traditional Chinese medicine composition may have a hepatoprotective effect; therefore, further HE staining of the liver showed that the traditional Chinese medicine composition could improve liver tissue morphology and reduce hepatic lipid deposition, with a better effect than losartan potassium. These results further suggest that the traditional Chinese medicine composition has a regulatory effect on glucose and lipid metabolism without hepatotoxic or nephrotoxic side effects.

[0084] Apoptosis is a crucial factor in the development of kidney disease (DKD). Studies have found that multiple factors, including glycolipid toxicity, angiotensin, and advanced glycation end products (AGEs), induce kidney tissue cell apoptosis through different pro-apoptotic pathways, thereby leading to the occurrence and progression of DKD. In this study, TUNEL staining was used to observe that all dosage groups of the traditional Chinese medicine composition could reduce the level of kidney tissue cell apoptosis in DKD mice.

[0085] definition

[0086] Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly used in the field to which this invention pertains. For the purposes of interpreting this specification, the following definitions will apply, and where appropriate, terms used in the singular will also include the plural forms, and vice versa.

[0087] Unless the context clearly indicates otherwise, the terms “a” and “an” as used herein include plural references.

[0088] The term "about" as used herein is as understood by one of ordinary skill in the art and varies within a certain range depending on the context in which it is used. If one of ordinary skill in the art is unfamiliar with the use of this term in the context in which it is used, "about" will mean a particular value plus or minus 10%.

[0089] As used herein, the term "pharmaceutically acceptable carrier" refers to a carrier or diluent that does not cause significant irritation to organisms and does not eliminate the biological activity and properties of the administered compound. It can be in various oral or parenteral formulations. Pharmaceutical compositions are formulated using conventional diluents or excipients, including fillers, fillers, binders, wetting agents, disintegrants, and surfactants. Examples include solid oral dosage forms or liquid oral dosage forms. Solid oral dosage forms include tablets, pills, powders, granules, capsules, etc. These solid dosage forms can be prepared by mixing at least one compound with one or more excipients, such as starch, calcium carbonate, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate or talc may also be used. Furthermore, liquid oral dosage forms include suspensions, solutions, and emulsions, etc. In addition to water, which is commonly used as a simple diluent, various excipients may be included, such as wetting agents, sweeteners, flavorings, preservatives, etc.

[0090] As used herein, the term "pharmaceuticalally effective dose" refers to a dose sufficient to treat the disease and a reasonable benefit / risk ratio suitable for any medical treatment. The effective dose level of the composition can be determined based on the subject's type, disease severity, age and sex, drug activity, drug sensitivity, time of administration, route of administration, excretion rate, duration of treatment, drugs used in combination with the composition, and other known factors in the medical field. The pharmaceutical compositions of the present invention can be used alone or in combination with other therapeutic agents, and can be administered sequentially or simultaneously with conventional therapeutic agents. The compositions can be administered in one or more dosage forms. Considering all the above factors, it is crucial to administer the composition at the minimum amount that will produce the maximum effect without causing side effects, which can be readily determined by those skilled in the art.

[0091] As used herein, the term "treatment" for a subject's disease or "treatment" for a subject who has or is suspected of having a disease refers to administering medication to a subject, such as one or more agents, to reduce or prevent the exacerbation of at least one symptom of the disease. Therefore, in one embodiment, "treatment" specifically refers to delaying progression, accelerating remission, inducing remission, increasing remission, accelerating recovery, increasing the efficacy of alternative therapies, or reducing resistance to alternative therapies, or combinations thereof.

[0092] The term "prevention" as used herein is recognized in the art and is well known in the art when used in connection with conditions such as local recurrence, and includes administration that reduces or delays the onset of medical symptoms in a subject relative to a subject who has not received the composition. The compositions of the present invention can be administered as food, such as a nutritional supplement. Generally, the compositions of the present invention are intended for the treatment of humans, although they can be used for the treatment of animals such as poultry, pigs, cats, dogs, horses, or rabbits. If administered to animals, oral feeding may be used.

[0093] The term "Ultra-High Performance Liquid Chromatography-Mass Spectrometry (UHPLC-MS)" as used in this article is a comprehensive analytical technique that combines the advanced separation performance of liquid chromatography with the high selectivity and sensitivity of mass spectrometry. It involves ionizing the sample in the form of a mobile phase under a liquid chromatographic separation system, then using a mass spectrometer to separate the ion fragments according to their mass numbers, and finally obtaining a mass spectrum through a mass spectrometry detection system. HPLC-MS is now widely used in fingerprint analysis of traditional Chinese medicine, food component detection, and pharmacokinetic analysis.

[0094] The term "hematoxylin and eosin (H&E) staining" as used in this article is one of the most commonly used staining methods in histology and pathology, suitable for preliminary observation of tissue structure and pathological changes. H&E staining stains cell nuclei a deep blue-purple and cytoplasm a pink color. In some implementations, H&E staining can be used to observe pathological changes in the kidneys and liver.

[0095] The term "periodic acid-Schiff (PAS) staining" as used in this article refers to the reaction of aldehyde groups in polysaccharides in tissues with Schiff's reagent to produce a purplish-red precipitate, thereby revealing glycogen-containing structures and staining the basement membrane purplish-red. In some implementations, PAS staining can be used to observe glycogen deposition in the kidneys and pathological changes in the renal tubules.

[0096] The term "Masson staining" used in this article is a classic connective tissue staining method that can clearly distinguish structures such as muscle, collagen fibers, and cell nuclei. It is suitable for the observation and quantification of collagen deposition and interstitial fibrosis in kidney tissue.

[0097] The term "terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL staining)" used in this article is a histological method for detecting apoptosis. The principle is to label the free 3'-OH groups at the ends of DNA breaks. During apoptosis, endogenous nucleases break DNA into oligonucleotide fragments, forming numerous 3'-OH ends. The TUNEL method utilizes terminal deoxynucleotidyl transferase (TdT) to attach labeled dUTPs (such as FITC-dUTP or HRP-dUTP) to these break sites, thereby revealing positive cells.

[0098] The term "tubular basement membrane (TBM)" used in this article refers to the extracellular matrix (ECM) layer located outside the basement membrane of all epithelial and endothelial cells in the body. It is a special form of ECM that separates the epithelium from the surrounding matrix, providing structural support for tissues and regulating the function of epithelial and endothelial cells. It is mainly composed of type IV collagen and laminin. The term "TUNEL staining" used in this article specifically detects DNA breaks generated during apoptosis. Since DNA breaks can occur in the early stages of apoptosis, combining it with DAPI staining can reflect the status of apoptosis. DAPI-stained cell nuclei appear blue under ultraviolet light excitation, while TUNEL-positive apoptotic cell nuclei appear green.

[0099] As used herein, the term "subject" refers to any animal, mammal, or human. The subject has, may have, or is suspected of having one or more diseases. In some embodiments, the subject is a human, monkey, chimpanzee, rabbit, mouse, rat, hamster, deer, goat, sheep, cow, pig, etc. In some embodiments, the subject has, may have, or is suspected of having one or more of the following: hyperlipidemia, diabetes, impaired liver function, or diabetic nephropathy.

[0100] The following embodiments and accompanying drawings are provided to aid in understanding the present invention. However, it should be understood that these embodiments and drawings are for illustrative purposes only and do not constitute any limitation. The actual scope of protection of the present invention is set forth in the claims. It should be understood that any modifications and changes can be made without departing from the spirit of the invention. The reagents and / or kits used in the following embodiments are commercially available or can be synthesized by known methods.

[0101] It should be noted that, unless specific conditions are specified in the examples, experimental conditions should be performed according to standard conditions, manufacturer recommendations, or publicly reported experimental conditions. Reagents or instruments whose manufacturers are not specified are all commercially available, standard products. For reagents whose manufacturers are specified, similar products from other manufacturers are substitutes.

[0102] Example

[0103] 1. Experimental reagents or consumables

[0104] The experimental reagents or consumables are shown in Tables 1-3.

[0105] Table 1. Experimental reagents used in Example 1

[0106]

[0107] Table 2. Reagents or consumables used in Example 2

[0108]

[0109] Table 3. Reagents or consumables used in Example 3

[0110]

[0111] 2. Experimental apparatus

[0112] The experimental apparatus is shown in Table 4.

[0113] Table 4. Experimental Apparatus

[0114]

[0115] 3. Experimental drugs

[0116] Astragalus membranaceus, Cuscuta chinensis, Hibiscus syriacus, Schisandra chinensis, Rosa laevigata, Euryale ferox, Pheretima aspergillum, Bombyx batryticatus, Arctium lappa, Rhus chinensis, Salvia miltiorrhiza, and Hedyotis diffusa were purchased from Beijing Tongrentang. Losartan potassium tablets (trade name: Cozaar, main ingredient is losartan potassium), repackaged by Hangzhou Merck Pharmaceutical Co., Ltd., drug approval numbers are HJ20171245 and HJ20171246, specification is 50mg / tablet. Dapagliflozin tablets (trade name: Andakang, main ingredient is dapagliflozin), repackaged by AstraZeneca Pharmaceutical Co., Ltd., drug approval numbers are HJ20170119 and HJ20170120, specification is 10mg / tablet.

[0117] 4. Laboratory animals

[0118] SPF-grade male C57BKS-db / db mice aged 8-9 weeks (hereinafter referred to as db / db) and wild-type C57BKS-wt / wt mice of the same age, same sex, and same genetic background (hereinafter referred to as wt / wt) (certificate number: No.111447231100099434) were purchased from Beijing Pharmacogene Biotechnology Co., Ltd. (production license number: SCXK (Beijing) 2023-0008). All experimental animals were housed separately in the SPF-class animal room of the Experimental Animal Center of Beijing University of Chinese Medicine's Liangxiang Campus (experimental animal use license number: SYXK (Beijing) 2016-0038). The feeding environment conditions were as follows: room temperature 22±2°C, relative humidity 50±10%, light and dark alternating cycle of 12h / 12h, and artificial light cycle was adopted. During the experiment, the mice could freely consume standard feed and drink purified water.

[0119] Preparation Example 1: Preparation Method 1 of Traditional Chinese Medicine Composition

[0120] A traditional Chinese medicine composition, calculated by weight parts, is as follows: 15 parts of Astragalus membranaceus, 10 parts of Cuscuta chinensis, 10 parts of Abelmoschus manihot flowers, 6 parts of Schisandra chinensis, 15 parts of Rosa laevigata, 15 parts of Euryale ferox, 10 parts of Pheretima aspergillum, 10 parts of Bombyx batryticatus, 10 parts of Arctium lappa, 10 parts of Galla chinensis, 15 parts of Salvia miltiorrhiza, 30 parts of Hedyotis diffusa.

[0121] Weigh the raw medicinal materials according to the above raw material ratio respectively. After mixing the medicinal materials according to the ratio, decoct and concentrate them with water to obtain a traditional Chinese medicine extract. [[ID=​​​​​​​​​​​​​​​​Weigh the raw materials according to the above proportions, mix the herbs according to the proportions, and then concentrate them by decoction to obtain a traditional Chinese medicine extract. Add dextrin and microcrystalline cellulose to the extract, mix, spray dry, granulate, sieve, and then granulate again to obtain granules.

[0128] Preparation Example 4: Method 4 for preparing traditional Chinese medicine compositions

[0129] A traditional Chinese medicine composition, wherein the traditional Chinese medicine composition comprises, by weight: 20 parts Astragalus membranaceus, 5 parts Cuscuta chinensis, 15 parts Hibiscus syriacus, 3 parts Schisandra chinensis, 10 parts Rosa laevigata, 10 parts Euryale ferox, 15 parts Pheretima aspergillum, 15 parts Bombyx mori, 12 parts Arctium lappa, 8 parts Galla chinensis, 18 parts Salvia miltiorrhiza, and 32 parts Hedyotis diffusa.

[0130] Weigh the raw materials according to the above proportions, mix the herbs according to the proportions, and then decoct and concentrate them to obtain a traditional Chinese medicine extract. Add dextrin and hydroxypropyl methylcellulose, mix well, and make into pills.

[0131] Experimental Example 1:

[0132] Water extract composition analysis

[0133] 1. Drug extraction

[0134] A traditional Chinese medicine composition, wherein the traditional Chinese medicine composition comprises, by weight, 15 parts Astragalus membranaceus, 10 parts Cuscuta chinensis, 10 parts Hibiscus syriacus, 6 parts Schisandra chinensis, 15 parts Rosa laevigata, 15 parts Euryale ferox, 10 parts Pheretima aspergillum, 10 parts Bombyx mori, 10 parts Arctium lappa, 10 parts Galla chinensis, 15 parts Salvia miltiorrhiza, and 30 parts Hedyotis diffusa.

[0135] Weigh the raw materials according to the above proportions, mix them according to the proportions, soak them in 10 times the amount of water for 2 hours, and extract by reflux for 2 hours. Repeat the extraction three times. Combine the extracts, filter and concentrate to obtain the water extract. Store the obtained water extract at -80℃ for later use.

[0136] 2. Drug pretreatment

[0137] (1) After the water extract samples were thawed, they were centrifuged at 12,000 rpm [centrifugal force 13,800 (×g), radius 8.6 cm] for 15 min at 4℃;

[0138] (2) Accurately pipette 300 μL of the supernatant and add 1000 μL of extraction buffer (methanol:acetonitrile:water (2:2:1, v / v / v)), the extraction buffer contains isotope-labeled internal standard;

[0139] (3) Vortex for 30 seconds, followed by ultrasonication in an ice-water bath for 5 minutes;

[0140] (4) Place it in a -20℃ refrigerator and let it stand for 1 hour;

[0141] (5) Centrifuge at 4℃, 12000rpm [centrifugal force 13800 (×g), radius 8.6cm] for 15min;

[0142] (6) Take the supernatant and filter it through a 0.22μm microporous membrane into a vial for instrumental testing.

[0143] 3. On-machine testing

[0144] The target compounds were separated chromatographically using a Vanquish (Thermo Fisher Scientific) ultra-high performance liquid chromatograph with a Phenomenex Kinetex C18 column (2.1 mm × 100 mm, 2.6 μm). Phase A of the liquid chromatography was aqueous containing 0.01% acetic acid, and phase B was isopropanol:acetonitrile (1:1, v / v). The sample pan temperature was 4 °C, and the injection volume was 2 μL.

[0145] The Orbitrap Exploris 120 mass spectrometer can perform primary and secondary mass spectrometry data acquisition under the control of software (Xcalibur, version 4.4, Thermo). Detailed parameters are as follows: Sheath gas flow rate: 50 Arb, Auxgas flow rate: 15 Arb, Capillary temperature: 320℃, Full ms resolution: 60000, MS / MS resolution: 15000, Collision energy: SNCE 20 / 30 / 40, Spray voltage: 3.8 kV (positive) or -3.4 kV (negative).

[0146] 4. Data Analysis

[0147] The raw data were converted to mzXML format using ProteoWizard software for metabolite identification. The databases used were TCM (V1.0) and BT-HERB (V1.0). This experiment was repeated twice.

[0148] Experimental results:

[0149] TIC Peak Chart

[0150] Mass spectrometry (MS) analysis was performed using both positive ion mode (POS) and negative ion mode (NEG) to obtain the total ion chromatogram (TIC) of the water extract concentrate. The top 10 substances based on the scoring values ​​were labeled and preliminarily identified.

[0151] like Figure 1 As shown, in positive ion mode, the main metabolites detected include nitrogen-containing small molecules such as choline, proline, and betaine; nucleosides and flavonoid glycosides such as vidarabine and protogenkwanin 4'-glucoside; and low-polarity small molecules such as isovaleramide and (R)-2-aminoheptane were detected in the later stages (approximately 10-11 minutes). Overall, positive ion mode is suitable for detecting nitrogen-containing basic metabolites, amino acid derivatives, glycosides, and other easily protonated components. Figure 2 As shown, in negative ion mode, compounds rich in readily deprotonated compounds forming negative ions were detected, including small-molecule organic acids such as malic acid, isocitric acid, erythronolactone, and gallic acid; polyphenolic components such as phloroglucinol and pyrogallol; and complex phenolic acids such as rosmarinic acid and salvianolic acid B, detected at a retention time of approximately 5 minutes. Overall, negative ion mode is suitable for detecting organic acids, polyphenols, and phenolic acids that readily lose protons (H+). + ) compounds.

[0152] Qualitative results

[0153] Mass spectrometry analysis revealed the top 30 most abundant substances in both positive and negative ion modes: 9 sugars and their derivatives (tacosyl, allose, D-glucopyranose, L-sorbose, glucose monohydrate, 1,3-dihydroxyacetone, DL-glyceraldehyde crystals, gluconic acid, erythritol lactone); 7 flavonoids (protocin 4'-glucoside, gossypol-8-O-glucuronide, isoquercitrin, hesperidin 7-O-glucoside, epigallocatechin, cyanidin, (+)-epigallocatechin); 6 amino acids and their derivatives (proline, betaine, DL-tryptophan, L-tryptophan, D-pyroglutamic acid, L-pyroglutamic acid); 6 alkaloids (2-piperidinone, flavonolactam, 1H-imidazol-1-acetic acid, (-)-carvirline, 2-amino-1-phenylethanol, norcolchicine); wood... Five types of lipoproteins (schisandrin, schisandrol A, arctigenin, pinoresinin 4-O-glucoside); five types of fatty acids and their derivatives ((R)-2-aminoheptane, malic acid, isocitrate, lactic acid, azelaic acid); five types of phenolic acids (tanshinone B, isostanshinone B, gallic acid, 5-galloylshikimic acid, pentagalloylglucoside); three types of phenylpropanoids (rosmarinic acid, cryptochlorogenic acid, p-hydroxycinnamic acid); and coumarins. Three types of compounds were identified: scopolamine, methylfraxin, and styracin; three types of terpenoids: chrysogenin D, deoxyrhonic acid, and dicotyl oleate BO-β-D-glucopyranoside; two types of isoflavones: 5-O-methylgenistein and daidzein; two types of nucleosides: adenosine and adenosine; two types of amides: oleamide and isovaleramide; two types of polyphenols: phloroglucinol and pyroglucinol; and one type of choline compound: choline.

[0154] Experimental Example 2: Effects on glucose and lipid metabolism, liver and kidney function, and urinary protein in diabetic nephropathy mice

[0155] A DKD animal model was established using db / db mice. The mice were treated with a traditional Chinese medicine composition. Dapagliflozin and losartan potassium, two Western medicines with different mechanisms of action, were used as positive controls. The effects of the traditional Chinese medicine composition on improving clinically relevant indicators such as glucose and lipid metabolism, liver and kidney function, and proteinuria were observed.

[0156] Experimental methods:

[0157] 1. Drug preparation

[0158] The ointment prepared in Example 1 was converted to a daily clinical dose of 1.52 g / kg for adults. Based on the equivalent dose ratio calculated from the body surface area of ​​humans and mice, the equivalent dose for mice was 9.1 times the adult dose, i.e., 13.83 g / kg / day. This dose was used as the medium dose for mice, with the low and high doses being 1 / 2 and 2 times the medium dose, respectively. The doses of the positive control drugs were also calculated using the same method based on the daily human dosage (dapagliflozin 50 mg / day, losartan potassium 50 mg / day). Considering the solubility of the positive control drugs, the drug solution was prepared in advance 1-2 days before administration. After the drug was prepared to the appropriate concentration using double-distilled water, it was first vortexed for 5 minutes, then sonicated at 37°C and 50 Hz for 30 minutes to ensure thorough mixing, and then stored in a refrigerator at 4°C. Before gavage, the drug solution was warmed in a 37°C water bath and vortexed and sonicated again to ensure homogeneity.

[0159] 2. Animal grouping and administration

[0160] After 4 weeks of acclimatization in the animal facility, fasting blood glucose and body weight were measured, and 24-hour urine was collected. Based on the 24-hour urinary protein, fasting blood glucose, and body weight levels, db / db mice were randomly divided into 6 groups using a random number table: model group (DN group), dapagliflozin group (DG group), losartan potassium group (LS group), low-dose group of traditional Chinese medicine composition (JD group or GSJD group), medium-dose group (JZ group or GSJZ group), and high-dose group (JG group or GSJG group); wt / wt mice were designated as the normal control group (ZC group). Mice in each group were administered the corresponding drugs via gavage at fixed times daily. The normal control group and model group received an equal volume of double-distilled water, and the administration continued for 8 weeks.

[0161] 3. Observation of general animal condition and indicators

[0162] During the animal rearing period, the general condition of each group of mice was closely observed, such as their mental state, responsiveness, hair density and color, defecation and urination, and activity level. The weight of the water bottles and feed was weighed regularly to calculate the average daily food and water intake of each group of mice.

[0163] 4. Specimen Collection

[0164] Starting from week 0 of drug administration, mice were transferred to metabolic cages every 4 weeks with free access to food and water. 24-hour urine was collected, and the urine volume was recorded. The collected urine was centrifuged at 2500 rpm for 15 minutes at 4°C. The supernatant was collected, aliquoted into 1.5 ml EP tubes, and stored at -80°C for subsequent analysis. Body weight was measured weekly during the drug administration period, and fasting blood glucose was measured every two weeks. Mice were fasted but allowed free access to water the night before fasting blood glucose measurement. Fasting blood glucose was measured the following morning at 8:00 AM using a portable rapid blood glucose meter via the tail vein.

[0165] Eight weeks after drug administration, mice were fasted for 12 hours but allowed free access to water before sampling. Mice were anesthetized by inhalation of isoflurane, and blood was collected after enucleation. The mice were then euthanized by cervical dislocation. The collected blood was allowed to stand at room temperature for 2 hours to allow for serum separation. Serum was then obtained by centrifugation at 4°C, 3000 rpm, for 15 minutes. The obtained serum was aliquoted and stored at -80°C for subsequent analysis. Kidney, liver, and colon tissues were collected from the mice. The weight of both kidneys and the liver was recorded, and a 1mm sample was collected. 3 Kidney tissue samples of appropriate size were fixed in electron microscopy fixative for subsequent observation of the ultrastructure under an electron microscope. Liver and kidney tissue samples were partially fixed in 4% paraformaldehyde for subsequent pathological observation, TUNEL apoptosis detection, and immunohistochemical experiments.

[0166] 5. Biochemical and urinary protein level detection

[0167] The collected urine and serum samples obtained 8 weeks after drug administration were analyzed by Beijing Beijian Xinchuangyuan Biotechnology Co., Ltd. using a Toshiba TBA40FR fully automated biochemical analyzer from Japan to measure the following indicators: total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum albumin (ALB), serum creatinine (Scr), blood urea nitrogen (BUN), blood uric acid (SUA), 24-hour urinary protein, urinary microalbumin, and urinary creatinine.

[0168] 6. Statistical Analysis

[0169] Statistical analysis was performed using IBM SPSS Statistics 26.0 software. For normally distributed data with homogeneous variance, one-way ANOVA was used for pairwise tests. Dunnett's test was used for data with unequal variances. For data that did not follow a normal distribution, the Kruskal-Wallis rank-sum test was used. P < 0.05 was considered statistically significant (compared to the model group, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001; compared to the normal group, #P < 0.05, ##P < 0.01, ###P < 0.001, ####P < 0.0001).

[0170] Experimental results:

[0171] 1. Effects on the general condition of mice

[0172] The normal wt / wt mice were in good spirits, slender, with thick, glossy fur, and were highly responsive and active. In contrast, the db / db model mice were lethargic, obese, with dull, thinning fur, slow responses to external stimuli, exhibiting sluggish movement, reluctance to move, and a preference for curling up; their bedding was noticeably damp. Compared to the model group, the mice in the traditional Chinese medicine intervention group, dapagliflozin group, and losartan potassium group showed increased activity, and their mental state, fur color, and responsiveness gradually improved.

[0173] 2. Effects on mouse body weight

[0174] Mice body weight was measured weekly from the start of administration, such as Figure 3 As shown, the body weight of mice in the ZC group remained stable. Compared with the ZC group, the body weight of db / db mice was significantly increased during the drug administration period (P<0.0001). The body weight of mice in the DN group showed a slight upward trend in the first 3 weeks, remained stable from weeks 3 to 6, and began to decline from weeks 6 to 8. The body weight of mice in the DG group showed an upward trend in the first 3 weeks, remained stable from weeks 3 to 7, and began to decline from weeks 7 to 8. The body weight of mice in the LS group and the traditional Chinese medicine administration group increased in the first week, and then gradually decreased, with the JG group showing the most significant decline. This may suggest that traditional Chinese medicine has a weight-reducing effect on db / db mice.

[0175] 3. Effects on organ weight and indices in mice

[0176] like Figure 4 As shown, compared with the ZC group, the kidney weight of mice in the DN group and all drug-treated groups was significantly increased (P<0.05). Compared with the DN group, the bilateral kidney weight of all drug-treated groups was decreased, with significant decreases in the JD and JZ groups (P<0.05). The kidney index is an important indicator of normal kidney function. Figure 5 As shown, compared with the ZC group, the kidney index of the DN group was increased but not significantly. Compared with the DN group, the kidney index of all treatment groups was significantly decreased (P<0.05), where kidney index = bilateral kidney weight (g) / body weight (g). This suggests that the traditional Chinese medicine composition has a reducing effect on the kidney index of db / db mice.

[0177] Changes in liver weight and liver index can macroscopically reflect the accumulation of fatty acids in the mouse liver, and can infer the degree of liver damage. For example... Figure 6 As shown, compared with the ZC group, the liver weight of mice in the model group and each drug-treated group was significantly higher than that in the normal group (P<0.0001). Compared with the DN group, the liver weight of the DG group was lower, the liver weight of the LS group was the same as that of the DN group, and the liver weight of the traditional Chinese medicine-treated groups showed a more obvious decreasing trend, especially the JD group, which showed the largest decrease, but the change was not statistically significant. Figure 7As shown, compared with the ZC group, the liver index of the DN group and all other treatment groups was increased, and the difference was statistically significant (P<0.0001). Compared with the DN group, the liver index of the DG group was significantly decreased (P<0.001), followed by the JZ group (P<0.01), and then the JD group (P<0.05). The liver index of the LS group and the JG group was lower than that of the DN group, but the difference was not statistically significant. The liver index is calculated as liver weight (g) / body weight (g). Analysis of the liver weight and liver index data shows that the traditional Chinese medicine group (low-to-medium dose group) can reduce the liver index, demonstrating its ability to improve liver damage in mice.

[0178] 4. Effects on fasting blood glucose in mice

[0179] like Figure 8 As shown, at week 0, the fasting blood glucose level of db / db mice (>20 mmol / L) was significantly higher than that of ZC group wt / wt mice (<10 mmol / L). In the DN group, fasting blood glucose showed an upward trend in the first two weeks, decreased slightly from weeks 2 to 4, but the mean value remained above 20 mmol / L, and then showed an upward trend after week 4. In the DG group, blood glucose showed a downward trend after administration, reaching its lowest point at week 4, and then increased again, but the blood glucose value was significantly lower than that of the DN group at each measurement (P<0.01). Compared with the DN group, the LS group slowed the upward trend of blood glucose and increased the downward trend of blood glucose. At week 6, the fasting blood glucose level was significantly lower than that of the DN group (P<0.01), after which blood glucose showed a significant upward trend, reaching a level close to that of the DN group at week 8. In the JD group, blood glucose showed an upward trend from weeks 0 to 2 and the blood glucose level was higher than that of the DN group. Blood glucose then began to decrease, reaching a level lower than that of the DN group at week 4. From weeks 4 to 8, blood glucose was relatively stable and lower than that of the DN group, but there was no statistical difference. The blood glucose levels in the JZ group also showed a trend of first increasing and then decreasing, with significantly lower levels than the DN group at week 6 (P<0.0001). Blood glucose levels began to rebound after week 6. Similarly, the blood glucose levels in the JG group showed a trend of first increasing, then decreasing, and then rising again, with significantly lower levels than the DN group at weeks 4 (P<0.05) and 6 (P<0.01). The data suggest that dapagliflozin has the fastest onset of action and the most significant hypoglycemic effect. The hypoglycemic effect in the traditional Chinese medicine group was generally observed within 2 weeks, and subsequent increases in blood glucose levels in db / db mice could be alleviated to varying degrees depending on the dosage.

[0180] 5. Effects on urine volume and urinary protein in mice

[0181] 5.1 Effects on 24-hour urine volume and 24-hour urinary protein in mice

[0182] like Figure 9As shown, at week 0 of administration, the 24-hour urine output of db / db mice increased compared to the ZC group, but the difference was not statistically significant. Compared to the DN group, there was no significant difference in urine output among the treatment groups. At week 4, the urine output of db / db mice increased significantly compared to the ZC group (P<0.0001), the urine output of mice in the DG group decreased significantly compared to the DN group (P<0.01), the urine output of the LS group decreased compared to the DN group, but the difference was not statistically significant, and the urine output of each dose group of the traditional Chinese medicine decreased significantly compared to the DN group (P<0.05). At week 8 of administration, the urine output of the DN group decreased significantly compared to week 4, but there was no significant difference compared to the ZC group. The urine output of the other treatment groups decreased compared to week 4, but the decrease was not as significant as that of the DN group.

[0183] like Figure 10 As shown, at week 0, 24-hour urinary protein levels in db / db mice were slightly higher than those in the ZC group, with no statistically significant difference. At weeks 4 and 8, 24-hour urinary protein levels in db / db mice were significantly higher than those in the ZC group (P<0.0001). In the DN group, 24-hour urinary protein levels increased sharply after week 0, reaching a peak at week 4. Compared to the DN group, the upward trend in 24-hour urinary protein levels in db / db mice in each treatment group slowed down, showing a decreasing trend from weeks 4 to 8. At week 4, 24-hour urinary protein levels in the DG, LS, JZ, and JG groups were significantly lower than those in the DN group (P<0.0001), while there was no significant difference in the decrease in 24-hour urinary protein levels between the JD and DN groups. At 8 weeks, compared with the DN group, the 24-hour urinary protein levels were significantly lower in the DG group (P<0.0001), LS group (P<0.0001), JD group (P<0.001), JZ group (P<0.0001), and JG group (P<0.0001). The results suggest that the traditional Chinese medicine group has a significant effect on improving 24-hour urinary protein levels.

[0184] 5.2 Effects on urinary albumin in mice

[0185] Urinary albumin excretion rate (UAER) can be used as an indicator to diagnose diabetic nephropathy and assess its progression. UAER is calculated in micrograms per 24 hours. Results are as follows... Figure 11As shown, at week 0, the UAER of db / db mice was slightly higher than that of the ZC group, with no statistically significant difference. At week 4, the UAER of db / db mice was significantly higher than that of the ZC group (P<0.001). The UAER of DN group mice showed a significant upward trend from week 0 to week 4, with the upward trend slowing down from week 4 to week 8. Compared with the DN group, the upward trend of UAER in db / db mice in each treatment group slowed down from week 0 to week 4, and the UAER showed a downward trend from week 4 to week 8. At week 4, the UAER of the DG, LS, JD, JZ, and JG groups was lower than that of the DN group, with the decrease in UAER in the JG group being significantly different (P<0.01). At week 8, compared with the DN group, the UAER of the DG (P<0.001), LS (P<0.01), JD (P<0.05), JZ (P<0.01), and JG (P<0.001) groups was significantly lower. The data results indicate that the traditional Chinese medicine group significantly improved UAER.

[0186] The urine protein / creatinine ratio (ACR) is a widely used indicator for evaluating kidney function. For example... Figure 12 As shown, the ACR in the ZC group remained stable. Compared with the ZC group, the ACR in db / db mice was significantly increased at week 0 (P<0.01). With the progression of the disease, the ACR in the DN group continued to rise, while the ACR in all treatment groups generally showed a decreasing trend. Compared with the DN group, the ACR in the LS group (P<0.05), JD group (P<0.01), JZ group (P<0.05), and JG group (P<0.01) was significantly decreased at week 4. At week 8, the ACR in the DG group (P<0.0001), LS group (P<0.001), JD group (P<0.0001), JZ group (P<0.0001), and JG group (P<0.0001) was significantly reduced. These results indicate that the traditional Chinese medicine treatment has a definite effect on ACR.

[0187] The data analysis above shows that the traditional Chinese medicine composition can reduce urinary albumin in db / db mice, has a kidney-protective effect, and can delay the occurrence and progression of diabetic nephropathy.

[0188] 6. Effects on renal function in mice

[0189] like Figure 13 As shown, compared with the ZC group, the Scr level in the DN group was significantly higher. Compared with the DN group, after 8 weeks of drug treatment, the Scr levels in the DG group (P<0.0001), LS group (P<0.0001), JD group (P<0.0001), JZ group (P<0.0001), and JG group (P<0.0001) were all significantly lower, with the JD group showing the largest decrease. These results indicate that the traditional Chinese medicine treatment has a significant effect on Scr levels.

[0190] like Figure 14As shown, compared with the ZC group, the DN group had an increased BUN level, but the difference was not statistically significant. After 8 weeks of drug intervention, the BUN levels in both the positive drug group and the traditional Chinese medicine group decreased, with statistically significant differences in the decreases observed in the DG group (P<0.01), LS group (P<0.01), JD group (P<0.01), and JG group (P<0.05).

[0191] like Figure 15 As shown, compared with the ZC group, the SUA level in the DN group was elevated, but the difference was not statistically significant. After 8 weeks of drug intervention, SUA levels decreased in both the positive drug group and the traditional Chinese medicine group, with the JD group showing the most significant effect (P<0.0001), while the DG group (P<0.05) and the LS group (P<0.01) showed significantly different reductions.

[0192] In summary, the traditional Chinese medicine composition has a positive effect on the renal function of db / db mice, with the low-dose group showing the best effect.

[0193] 7. Effects on lipid metabolism in mice

[0194] The statistical analysis results of triglycerides in mice are as follows: Figure 16 The results showed that the TG value in the DN group was significantly higher than that in the ZC group (P<0.0001). After 8 weeks of drug intervention, the TG value decreased in both the positive drug group and the traditional Chinese medicine group, with the DG group showing the most significant decrease (P<0.0001).

[0195] Total cholesterol analysis results as follows Figure 17 As shown, compared with group ZC, the TC value in group DN was significantly increased (P<0.0001). After 8 weeks of drug intervention, the TC values ​​in groups DG (P<0.0001), LS (P<0.0001), JD (P<0.0001), JZ (P<0.0001), and JG (P<0.0001) all decreased significantly, with the JD group showing the most significant decrease. The results indicate that the traditional Chinese medicine composition has a significant intervention effect on total cholesterol.

[0196] The results of the analysis of high-density lipoprotein cholesterol are as follows: Figure 18 As can be seen, there was no significant change in HDL-C in the DN group compared with the ZC group. After 8 weeks of drug intervention, HDL-C values ​​in the DG group (P<0.0001), LS group (P<0.0001), JD group (P<0.01), JZ group (P<0.0001), and JG group (P<0.0001) all increased significantly. The results indicate that the traditional Chinese medicine composition has a definite effect on high-density lipoprotein cholesterol.

[0197] The results of the analysis of low-density lipoprotein cholesterol are as follows: Figure 19As can be seen, compared with the ZC group, the LDL-C level in the DN group was significantly increased (P<0.0001). After 8 weeks of drug intervention, the LDL-C values ​​in the DG group (P<0.0001), LS group (P<0.0001), JD group (P<0.0001), JZ group (P<0.0001), and JG group (P<0.0001) all decreased significantly, with the JD group showing the most significant decrease. The results indicate that the traditional Chinese medicine composition has a significant positive intervention effect on low-density lipoprotein cholesterol.

[0198] In summary, the traditional Chinese medicine composition has a positive regulatory effect on blood lipids, especially total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol, in db / db mice.

[0199] 8. Effects on liver function in mice

[0200] like Figure 20 As shown, compared with the ZC group, the ALT level in the DN group was significantly increased (P<0.0001). After 8 weeks of drug intervention, compared with the DN group, the ALT levels in all drug-treated groups decreased, with the JG group showing the most significant decrease (P<0.0001).

[0201] like Figure 21 As shown, compared with the ZC group, the AST in the DN group did not change significantly. After drug intervention, the AST in the LS group and JD group increased. The AST in each drug administration group did not change significantly compared with the ZC group and the DN group.

[0202] like Figure 22 As shown, compared with the ZC group, there was no significant change in serum albumin (ALB) in the DN group. After drug intervention, the serum albumin in the drug-treated group increased. Compared with the ZC group, the differences in DG group (P<0.05), LS group (P<0.001), JD group (P<0.05) and JZ group (P<0.01) were significant. Compared with the DN group, the increase in LS group (P<0.05) was significant.

[0203] In summary, the analysis shows that the traditional Chinese medicine composition did not cause significant liver damage in db / db mice, and could improve liver function indicators to a certain extent.

[0204] Example 3. Effects on organ morphology and pathology in diabetic nephropathy mice

[0205] 1. HE staining

[0206] like Figure 23As shown in Example 2, HE staining results of mouse livers obtained after 8 weeks of drug administration in each group showed that the liver morphology and structure of mice in the ZC group were normal, with clear hepatic cords, tightly and regularly arranged hepatocytes, and no obvious inflammatory cell infiltration, fibrosis, or fatty degeneration. Compared with the ZC group, the liver morphology and structure of mice in the DN group were significantly disordered, with indistinct hepatic cords, irregular hepatocyte arrangement, and varying degrees of swelling. Hepatocytes were filled with fat droplets or fat vesicles, compressing the nuclei and organelles of normal hepatocytes, indicating significant fatty degeneration of the liver. After intervention with positive control drugs (especially dapagliflozin) and traditional Chinese medicine, the liver structure of mice became clearer, the hepatic cords became more regular, and the number of hepatocytes with vacuolar changes decreased. The results indicate that the traditional Chinese medicine composition can effectively reduce the number of hepatic fat droplets and significantly improve hepatic fatty degeneration, suggesting that the traditional Chinese medicine composition can protect against liver damage during the DKD process.

[0207] like Figure 24 As shown in Example 2, HE staining of the kidneys of mice in each group after 8 weeks of drug administration revealed that in the ZC group, the size and structure of the glomeruli were normal, the capillary plexus was sufficiently dilated, the renal tubules had clear outlines, regular lumens, and were neatly arranged, and the morphology of the renal tubular epithelial cells was normal. In the DN group, the glomeruli were enlarged and structurally disordered, and local renal tubular epithelial cells showed swelling, degeneration, or necrosis. A large number of inflammatory cells infiltrated the glomeruli, especially the renal tubular lumen and renal interstitium. After 8 weeks of drug intervention, the glomerular and tubular lesions in each treatment group were alleviated, and the inflammatory cell infiltration decreased. This demonstrates that the traditional Chinese medicine composition can improve the pathological structure of the kidneys in DKD mice and reduce renal inflammatory lesions.

[0208] 2. PAS staining

[0209] PAS staining was used to detect glycogen deposition in the kidneys of mice in each group, and pathological changes in renal tubular epithelial cells and renal tubular basement membrane were observed. Figure 25 As shown, in the ZC group, the renal tubular epithelial cells were morphologically normal and neatly arranged, with thin and regular TBMs and little glycogen deposition. In the DKD group, glycogen deposition was visible in the renal tubular epithelial cells, brush border destruction was reduced, and the TBM staining was darker and thicker. After drug intervention, the amount of glycogen deposition in the renal tubules was significantly reduced, the morphology of the renal tubular epithelial cells improved, and the TBM thickness tended to normalize. Quantitative analysis of TBM thickness showed that the drug-treated groups significantly reduced TBM thickness to varying degrees (P < 0.0001). This indicates that the traditional Chinese medicine composition can effectively improve glucose metabolism in DKD mice, promote glycogen excretion, and improve renal tubular pathological changes.

[0210] 3. Masson staining

[0211] Masson staining stained collagen fibers blue and muscle and cytoplasm red. Masson staining can be used to observe the degree of kidney fibrosis. For example... Figure 26As can be seen, compared with the ZC group, the DN group showed expansion of the glomerular mesangial area, increased collagen deposition, significantly widened peritubular interstitium, and a marked increase in blue collagen fiber deposition, accompanied by tubular atrophy, tubular epithelial degeneration, and inflammatory cell infiltration. After drug intervention, the renal tissue structure recovered somewhat, the blue fiber area shrank significantly, interstitial collagen deposition decreased, and the glomerular and tubular basement membrane structures tended to normalize. Quantitative analysis of the collagen fiber area ratio also showed that the drug-treated group significantly reduced collagen fiber deposition in the DN group (P < 0.0001). The results suggest that the traditional Chinese medicine composition can improve renal fibrosis in DKD mice.

[0212] 4. TUNEL staining

[0213] like Figure 27 As shown, TUNEL-positive cells were almost invisible in the ZC group. Compared with the ZC group, the number of apoptotic cells in the DN group was significantly increased. The number of apoptotic cells decreased after intervention with the positive control drug and the traditional Chinese medicine combination. This indicates that the traditional Chinese medicine combination can inhibit apoptosis of kidney cells in DKD mice.

[0214] 5. Transmission electron microscopy observation

[0215] Using transmission electron microscopy, we can observe the damage to the glomerular filtration barrier structure in the kidneys of DKD mice. For example... Figure 28 As can be seen, in the ZC group, the foot processes were regularly arranged and clearly distinguishable, and the basement membrane thickness was uniform and continuous; in the DN group, extensive fusion or even disappearance of the foot processes was observed, the glomerular basement membrane was significantly thickened, and electron-dense deposits were visible; in the drug-treated group, the foot process structure was significantly improved, fusion was reduced, and the basement membrane thickness tended to be normal. The results suggest that the traditional Chinese medicine composition can improve the pathological changes of the foot processes and glomerular basement membrane in DKD mice, reduce the abnormal deposition of basement membrane components such as type IV collagen and fibronectin, and protect the glomerular filtration barrier structure.

[0216] The technical solutions of the present invention are not limited to the specific embodiments described above. Any technical modifications made in accordance with the technical solutions of the present invention fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for lowering blood sugar and lipids, made from the following traditional Chinese medicinal materials in parts by weight: Astragalus membranaceus 10-20 parts, Cuscuta chinensis 5-18 parts, Hibiscus syriacus 5-18 parts, Schisandra chinensis 1-15 parts, Rosa laevigata 10-20 parts, Euryale ferox 10-20 parts, Pheretima aspergillum 5-18 parts, Bombyx mori 5-18 parts, Arctium lappa 5-18 parts, Galla chinensis 5-18 parts, Salvia miltiorrhiza 10-20 parts, and Hedyotis diffusa 20-40 parts.

2. The traditional Chinese medicine composition as described in claim 1 is made from the following traditional Chinese medicinal materials in parts by weight: 15 parts Astragalus membranaceus, 10 parts Cuscuta chinensis, 10 parts Hibiscus syriacus, 6 parts Schisandra chinensis, 15 parts Rosa laevigata, 15 parts Euryale ferox, 10 parts Pheretima aspergillum, 10 parts Bombyx mori, 10 parts Arctium lappa, 10 parts Galla chinensis, 15 parts Salvia miltiorrhiza, and 30 parts Hedyotis diffusa.

3. The traditional Chinese medicine composition as described in claim 1, made from the following traditional Chinese medicinal materials in parts by weight: 12 parts Astragalus membranaceus, 8 parts Cuscuta chinensis, 14 parts Hibiscus syriacus, 9 parts Schisandra chinensis, 12 parts Rosa laevigata, 10 parts Euryale ferox, 13 parts Pheretima aspergillum, 12 parts Bombyx mori, 15 parts Arctium lappa, 6 parts Galla chinensis, 20 parts Salvia miltiorrhiza, 34 parts Hedyotis diffusa, and / or; Made from the following Chinese medicinal materials in parts by weight: Astragalus membranaceus 10 parts, Cuscuta chinensis 15 parts, Hibiscus syriacus 6 parts, Schisandra chinensis 11 parts, Rosa laevigata 20 parts, Euryale ferox 20 parts, Pheretima aspergillum 5 parts, Bombyx mori 5 parts, Arctium lappa 5 parts, Galla chinensis 15 parts, Salvia miltiorrhiza 10 parts, Hedyotis diffusa 25 parts, and / or; It is made from the following Chinese medicinal materials in parts by weight: Astragalus membranaceus 20 parts, Cuscuta chinensis 5 parts, Hibiscus syriacus 15 parts, Schisandra chinensis 3 parts, Rosa laevigata 10 parts, Euryale ferox 10 parts, Pheretima aspergillum 15 parts, Bombyx mori 15 parts, Arctium lappa 12 parts, Galla chinensis 8 parts, Salvia miltiorrhiza 18 parts, and Hedyotis diffusa 32 parts.

4. A formulation comprising the traditional Chinese medicine composition according to any one of claims 1 to 3 and pharmaceutically acceptable excipients.

5. The formulation of claim 4, comprising one or more of the following: decoction, extract, pill, powder, granule, and capsule.

6. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3, or the preparation according to claim 4 or 5, in the preparation of a medicament for the prevention or treatment of hyperlipidemia, diabetes, or diabetic nephropathy.

7. The application as described in claim 6, wherein the drug can be used for any one or more of the following: 1) Reduce weight; 2) Maintain lipid metabolism balance; 3) Maintain blood sugar balance; 4) Protect or improve kidney and / or liver function; 5) Delay the onset of diabetic nephropathy.

8. The application as described in claim 7, wherein maintaining lipid metabolism balance includes improving lipid metabolism disorders or abnormalities, preferably including one or more of the following: significantly improving abnormally elevated triglyceride levels, significantly improving abnormally elevated total cholesterol levels, significantly increasing high-density lipoprotein cholesterol levels, and significantly improving abnormally elevated low-density lipoprotein cholesterol levels; and / or, Maintaining blood glucose balance includes improving glucose metabolism disorders or abnormalities and / or improving abnormally high fasting blood glucose levels.

9. The application as described in claim 7, wherein the protection or improvement of renal function includes one or more of the following: improving abnormally decreased water intake, maintaining stable urine output, improving abnormally elevated urine protein levels, alleviating renal inflammatory lesions, improving renal collagen deposition and fibrosis, inhibiting renal cell apoptosis or improving abnormally elevated renal index, reducing glycogen deposition in renal tubules, improving pathological changes in renal tubular epithelial cells, improving abnormally thickened basement membrane, improving renal fibrosis, improving increased abnormal renal cell apoptosis, alleviating glomerular and tubular lesions, reducing inflammatory cell infiltration, improving pathological changes in renal foot processes and glomerular basement membranes, reducing abnormal deposition of basement membrane components such as type IV collagen and fibronectin, and protecting the glomerular filtration barrier structure.

10. The application as described in claim 7, wherein the protection or improvement of liver function includes prevention and / or treatment of liver damage caused by diabetic nephropathy, preferably including one or more of the following: improving abnormally elevated alanine aminotransferase, improving pathological structural changes in the liver, and reducing liver index in the subject.

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