A Chinese medicine composition for lowering blood sugar, protecting kidneys and resisting aging, as well as its preparation and preparation method

Abstract

The present invention discloses a traditional Chinese medicine composition for lowering blood sugar, protecting the kidney and anti-aging, as well as its preparation and preparation method, belonging to the field of traditional Chinese medicine pharmacy of Antang Yishen Formula. A traditional Chinese medicine composition for lowering blood sugar, protecting the kidney and anti-aging is composed of the following components in parts by weight: 3-4 parts of Radix Rehmanniae Extract, 2-3 parts of Fructus Corni Extract, 3-4 parts of Ampelopsis grossedentata Extract, 3-4 parts of Polygonatum sibiricum Extract, 3-4 parts of Phellinus igniarius Extract, 3-4 parts of Poria cocos Extract, 3-5 parts of Dioscorea opposita Extract and 1 part of Rhizoma Coptidis Extract. The traditional Chinese medicine composition provided by the present invention can significantly reduce the blood sugar level of diabetes, improve the condition of diabetic nephropathy and delay the disease progression, and has good safety.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine pharmaceutical technology, and more specifically, to a traditional Chinese medicine composition for lowering blood sugar, protecting the kidneys, and anti-aging, as well as its preparation and preparation method. Background Technology

[0002] Diabetic kidney disease (DKD) is a significant and highly dangerous microvascular complication in diabetic patients, and a leading cause of end-stage renal disease (ESRD). Clinically, DKD is characterized by persistent albuminuria and / or a progressive decline in glomerular filtration rate (GFR), which may eventually progress to ESRD. Currently, clinical treatment for DKD includes both pharmacological and non-pharmacological approaches. Non-pharmacological treatments encompass lifestyle interventions, weight loss, smoking cessation, alcohol restriction, blood pressure control, and lipid regulation. Classical treatments primarily rely on angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). However, due to the uncertain efficacy and significant side effects of existing drugs, developing new treatment strategies and medications is crucial for improving the prognosis of DKD patients.

[0003] Modern medicine considers the pathogenesis of diabetic kidney disease (DKD) to be quite complex, involving multiple aspects such as oxidative stress, inflammation, and autophagy. Therefore, compared to single-target drugs, Traditional Chinese Medicine (TCM), with its multi-target, multi-pathway, multi-level, multi-system, and multi-time-limit holistic dynamic fine-tuning and early-regulation effects, can exert its effects through multiple pathways, including reducing inflammatory responses, lowering oxidative stress, and regulating cellular autophagy, thus demonstrating significant advantages in the prevention and treatment of diabetic nephropathy. TCM's understanding and research on diabetic nephropathy has a long history. As early as the *Huangdi Neijing* (Yellow Emperor's Inner Classic), the disease name "Xiao Ke" (wasting and thirsting) was proposed: "This is caused by excessive consumption of rich and delicious foods. Such a person must frequently eat sweet and fatty foods. Fat causes internal heat, and sweet foods cause fullness in the middle, so the qi overflows upwards, turning into Xiao Ke." Later, the *Jinkui Yaolue* (Essential Prescriptions of the Golden Chamber) recorded the clinical manifestations of Xiao Ke: "When qi is abundant, urination is frequent; frequent urination becomes hard; the combination of frequent and hard urination is Xiao Ke." Based on this passage, Xiao Ke is equivalent to diabetes in modern medicine. Later, the disease name "Kidney Wasting" was introduced in *Zhengzhi Zhunsheng* (Standards for Diagnosis and Treatment). The text states: "Excessive thirst and drinking is Upper Wasting (referred to as Diaphragmatic Wasting in the classics); excessive hunger is Middle Wasting (referred to as Middle Wasting in the classics); Frequent thirst and urination with viscous stools is Lower Wasting (referred to as Kidney Wasting)." This "Kidney Wasting" is equivalent to diabetic nephropathy in modern medicine. Finally, in Volume 53 of *Taiping Shenghui Fang* (Prescriptions for Universal Relief), a more detailed description of diabetic nephropathy is given: "Water is consumed with urination, urine is sweet and cloudy, and there is emaciation in the waist and legs; this is Kidney Wasting." This description clearly indicates that patients with diabetic nephropathy will exhibit proteinuria.

[0004] In Traditional Chinese Medicine (TCM), the basic pathogenesis of diabetes mellitus (Xiao Ke) is attributed to Yin deficiency and dryness-heat. Yin deficiency is the root cause, while dryness-heat is the manifestation; the two are mutually causal. The more deficient the Yin, the more intense the dryness-heat, and vice versa, creating a vicious cycle. The disease primarily involves the lungs, stomach, and kidneys, with the kidneys being particularly crucial. These three organs influence each other, yet each has its own emphasis. The lungs are the upper source of water, distributing body fluids. If dryness-heat damages the lungs, body fluids cannot be distributed and instead flow downwards, resulting in frequent and copious urination. Impaired lung function leads to thirst and excessive drinking. If dryness-heat damages the spleen and stomach, excessive stomach fire and insufficient spleen Yin result in thirst, excessive drinking, and increased hunger. Spleen deficiency impairs transport and transform, causing the essence of food and water to flow downwards into the urine, resulting in a sweet-tasting urine. Depletion of the essence of food and water leads to gradual emaciation. If diabetes persists for a long time and the condition becomes uncontrolled, it can damage both Yin and Yang, leading to heat scorching body fluids, blood stasis, and ultimately, deficiency of both Qi and Yin. This results in obstruction of the collaterals and damage to internal organs, causing complications such as boils, carbuncles, dizziness, chest pain, deafness, blindness, numbness and pain in the limbs, gangrene of the lower limbs, renal failure with edema, or stroke and coma. Traditional Chinese medicine (TCM) has demonstrated unique advantages in improving the clinical symptoms of DKD patients, enhancing their quality of life, and halting the progression of the disease. Through syndrome differentiation and treatment, TCM can not only effectively control blood sugar, reduce proteinuria, and eliminate edema, but also slow the progression of Chronic Kidney Disease (CKD) through external therapies, thereby significantly improving patients' quality of life. Summary of the Invention

[0005] To address the problems existing in the prior art, the first objective of this invention is to provide a traditional Chinese medicine composition for lowering blood sugar, protecting the kidneys, and anti-aging. The second objective of this invention is to provide a traditional Chinese medicine composition formulation. The third objective of this invention is to provide a method for preparing the traditional Chinese medicine composition. The traditional Chinese medicine composition provided by this invention has high safety and has shown efficacy in lowering blood sugar, protecting the kidneys, and anti-aging in pharmacological experiments. It can be used to treat diabetic nephropathy (DKD).

[0006] To solve the above problems, the present invention adopts the following technical solution.

[0007] A traditional Chinese medicine composition for lowering blood sugar, protecting the kidneys, and anti-aging is composed of the following ingredients in the indicated weight proportions: 3-4 parts Rehmannia glutinosa extract, 2-3 parts Cornus officinalis extract, 3-4 parts Chaenomeles speciosa extract, 3-4 parts Polygonatum sibiricum extract, 3-4 parts Phellinus linteus extract, 3-4 parts Poria cocos extract, 3-5 parts Dioscorea opposita extract, and 1 part Coptis chinensis extract.

[0008] This invention also provides a method for preparing a traditional Chinese medicine composition that lowers blood sugar, protects the kidneys, and has anti-aging effects, comprising the following steps: first, extracts of Rehmannia glutinosa, Cornus officinalis, vine tea, Polygonatum sibiricum, Phellinus linteus, Poria cocos, Dioscorea opposita, and Coptis chinensis from the traditional Chinese medicine composition are obtained by the following method:

[0009] (1) Crush the raw Rehmannia root, add 6 to 10 times the amount of water and decoct 2 to 3 times, 1 hour each time. Remove the residue and combine the decoction with the filtrate. Concentrate the filtrate under reduced pressure at 70 to 90°C to obtain the extract. Freeze-dry the extract under vacuum and pulverize it through a No. 6 sieve to obtain the raw Rehmannia root extract powder.

[0010] (2) Crush the Cornus officinalis, add 6 to 10 times the amount of water and decoct 2 to 3 times, 1 hour each time. Remove the residue and combine the decoction with the filtrate. Concentrate the filtrate under reduced pressure at 70 to 90°C to obtain an extract. Freeze-dry the extract under vacuum and pulverize it through a No. 6 sieve to obtain Cornus officinalis extract powder.

[0011] (3) Add 6 to 10 times the amount of water to the vine tea and decoct 2 to 3 times, 1 hour each time. Remove the residue and combine the decoction with the filtrate. Concentrate the filtrate under reduced pressure at 70 to 90°C to obtain an extract. Freeze-dry the extract under vacuum and pulverize it through a No. 6 sieve to obtain vine tea extract powder.

[0012] (4) Add 6 to 10 times the amount of water to the Polygonatum and decoct 1 to 2 times, 1 hour each time. Remove the residue and combine the decoction with the filtrate. Concentrate the filtrate under reduced pressure at 70 to 90°C to obtain the extract. Freeze-dry the extract under vacuum and pulverize it through a No. 6 sieve to obtain Polygonatum extract powder.

[0013] (5) Add 6 to 10 times the amount of water to decoct 2 to 3 times, 1 hour each time, remove the residue and take the decoction and combine the filtrate. Concentrate the filtrate under reduced pressure at 70 to 90°C to obtain the extract. Freeze-dry the extract under vacuum and pulverize it through a No. 6 sieve to obtain mulberry extract powder.

[0014] (6) Add 6 to 10 times the amount of water to Poria cocos and decoct 2 to 3 times, 1 hour each time. Remove the dregs and combine the decoction with the filtrate. Concentrate the filtrate under reduced pressure at 70 to 90°C to obtain an extract. Freeze-dry the extract under vacuum and pulverize it through a No. 6 sieve to obtain Poria cocos extract powder.

[0015] (7) Add 6 to 10 times the amount of water to the yam and decoct 2 to 3 times, 1 hour each time. Remove the residue and combine the decoction with the filtrate. Concentrate the filtrate under reduced pressure at 70 to 90°C to obtain an extract. Freeze-dry the extract under vacuum and pulverize it through a No. 6 sieve to obtain yam extract powder.

[0016] (8) Add 5 to 10 times the amount of water to Coptis chinensis and decoct 2 to 3 times, 1 hour each time. Remove the dregs and combine the decoction with the filtrate. Concentrate the filtrate under reduced pressure at 70 to 90°C to obtain an extract. Freeze-dry the extract under vacuum and pulverize it through a No. 6 sieve to obtain Coptis chinensis extract powder.

[0017] Finally, the powdered extracts of the following eight herbs—Rehmannia glutinosa, Cornus officinalis, vine tea, Polygonatum sibiricum, Phellinus linteus, Poria cocos, Dioscorea opposita, and Coptis chinensis—are mixed in a certain proportion.

[0018] The present invention also provides a traditional Chinese medicine composition preparation for lowering blood sugar, protecting the kidneys, and anti-aging, wherein the traditional Chinese medicine composition preparation comprises the above-mentioned traditional Chinese medicine composition and appropriate amounts of other raw materials.

[0019] Furthermore, the traditional Chinese medicine composition preparation is a tablet, chewable tablet, powder, granule, powder, capsule, ointment, pill or liquid preparation.

[0020] Furthermore, the traditional Chinese medicine composition preparation also includes food additives.

[0021] Rehmannia glutinosa, scientifically known as *Rehmanniae Radix*, is the fresh or dried tuberous root of the plant *Rehmannia glutinosa* Libosch., belonging to the Scrophulariaceae family. It has a sweet and bitter taste, is cold in nature, and enters the heart, liver, and kidney meridians. It possesses the effects of clearing heat and promoting body fluid production, nourishing yin and tonifying the kidneys, and cooling the blood and stopping bleeding. Furthermore, it has the effect of resolving blood stasis: The *Pharmacopoeia of Chinese Materia Medica* mentions that it can "resolve various heats, break up blood stasis, promote menstruation, and also benefit urination; when crushed and applied to the heart and abdomen, it can eliminate blood stasis." This indicates that it has the effect of promoting blood circulation and removing blood stasis. Rehmannia glutinosa was first recorded in the *Shennong's Classic of Materia Medica* during the Han Dynasty, which mentions that it can "expel blood stasis and eliminate numbness," where "numbness" refers to rheumatism. It can improve conditions of insufficient blood and poor blood circulation. Pharmacological studies have shown that the active ingredients of Rehmannia glutinosa have multiple effects, including promoting hematopoiesis, lowering blood sugar, lowering blood lipids, lowering blood pressure, anti-inflammation, and improving insulin resistance. These effects are especially important for people with diabetes, as they can not only lower blood sugar but also reduce complications caused by diabetes.

[0022] Cornus officinalis, scientifically known as Corni Fructus, is the dried, mature fruit pulp of the plant Cornus officinalis Sieb. et Zucc., belonging to the Cornaceae family. Cornus officinalis has a sour and astringent taste, is slightly warm in nature, and enters the liver and kidney meridians. It has the effects of tonifying the liver and kidneys, astringing essence and consolidating the body, and stopping bleeding. The *Shennong Bencao Jing* (Shennong's Classic of Materia Medica) records that Cornus officinalis "treats evil qi in the heart, chills and fever, warms the middle jiao, expels cold and dampness, eliminates three parasites, and long-term use leads to lightness of body." Modern research shows that Cornus officinalis has effects such as lowering blood sugar, lowering blood lipids, anti-oxidation, and anti-aging. Specific research results indicate that Cornus officinalis polysaccharides can, in vitro, concentration-dependently enhance glucose uptake in insulin-resistant HepG2 cells and significantly improve glucose consumption. In vivo, Cornus officinalis polysaccharides can significantly reduce fasting blood glucose levels, glycated hemoglobin levels, and amylase activity in streptozotocin (STZ)-induced diabetic rats. Furthermore, Cornus officinalis extract can improve the expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and nuclear factor-κB (NF-κB) in macrophages induced by lipopolysaccharide (LPS), thereby protecting the kidneys by downregulating protein kinase B (AKT) phosphorylation and thus improving diabetic nephropathy (DKD). These pharmacological effects are the key mechanism by which Cornus officinalis exerts its anti-DKD effect.

[0023] Vine tea, scientifically known as *Ampelopsis grossedentata*, is the dried stem and leaves of *Ampelopsis grossedentata* (Handel-Mazzetti) Wt. Wang, a plant in the Vitaceae family. The *Classic of Poetry* records that vine tea was first called "Ancient Tea Hook Vine." Lu Yu, a tea master of the Tang Dynasty, named it vine tea in his *Classic of Tea*, a name that has remained to this day. Vine tea is green in color with a white frost-like appearance. It has a slightly bitter initial taste, but a long-lasting and refreshing sweetness. Vine tea is sweet, bland, and slightly astringent in taste, and is cool in nature. It enters the lung, liver, kidney, and stomach meridians, and has the effects of clearing heat and detoxifying, promoting diuresis and reducing swelling, purging fire and calming the liver, invigorating blood and removing turbidity, and detoxifying alcohol. Clinically, it is often used for colds with fever, sore throat, mouth ulcers, carbuncles and boils, damp-heat jaundice, dysentery, diarrhea, painful urination, red and swollen eyes, headache and dizziness, blood turbidity disease (hyperlipidemia), and alcohol poisoning. A clinical trial showed that one month of vine tea intervention significantly reduced fasting plasma glucose (FPG), glycated albumin (GA), cystatin C, and retinol-binding protein 4 (RBP4) levels in adults with type 2 diabetes, thereby significantly improving renal function in these patients. Studies have shown that the main active ingredients in vine tea are flavonoids such as dihydromyricetin (DHM), which possess multiple effects including hypoglycemic, antioxidant, alcohol-protective, antitumor, anti-inflammatory, antimicrobial, and antithrombotic properties. For example, DHM can alleviate abnormally high blood glucose levels in Zucker diabetic obese rats by inhibiting PPARγ phosphorylation; in db / db mice, DHM can also improve insulin resistance by upregulating IRS-1 tyrosine phosphorylation levels.

[0024] Polygonatum, scientifically known as *Polygonati Rhizoma*, is the dried rhizome of *Polygonatum kingianum* Coll. et Hemsl., *Polygonatum sibiricum* Red., or *Polygonatum cyrtonema* Hua, all belonging to the Liliaceae family. It is sweet in taste and neutral in nature, entering the spleen, lung, and kidney meridians. It possesses the functions of tonifying qi and nourishing yin, strengthening the spleen and replenishing qi, nourishing yin and moistening the lungs, and tonifying the kidneys and replenishing essence. Pharmacologically, Polygonatum exhibits various effects, including lowering blood sugar, lowering blood pressure, lowering blood lipids, enhancing immunity, anti-fatigue, improving memory, and anti-oxidation. These effects not only help effectively control the overall symptoms of diabetic patients but also significantly improve chronic kidney damage. Studies have shown that aqueous extracts of Polygonatum can enhance the expression of the glucose transporter 4 (GLUT-4) gene in type 2 diabetes mellitus (T2DM) rats, thereby lowering blood sugar. In addition, Polygonatum extract can significantly reduce blood glucose levels in alloxan-induced diabetic mice and reduce hyperglycemia caused by adrenaline or exogenous glucose.

[0025] Sanghuang, scientifically known as *Sanghuangporus*, is the dried fruiting body of the fungus *Sanghuangporus vaninii* (Ljub) LWZhou et YCDai, belonging to the family Phycotaeceae. Sanghuang is a highly valuable large medicinal fungus, with a sweet, pungent, and slightly bitter taste. It is cold in nature, non-toxic, and enters the liver and kidney meridians, possessing the effects of tonifying the liver and kidneys and strengthening tendons and bones. In traditional Chinese medicine, Sanghuang is used to treat various symptoms caused by liver and kidney deficiency and has a certain protective effect on patients with diabetic nephropathy. Modern pharmacological studies show that Sanghuang contains various active ingredients such as polysaccharides, flavonoids, triterpenes, and polyphenols, possessing antioxidant, antitumor, immunomodulatory, anti-inflammatory, and hypoglycemic effects. Studies have found that Sanghuang polysaccharides can effectively improve glucose tolerance in diabetic mice and significantly reduce their fasting blood glucose levels. Furthermore, Sanghuang polysaccharides can alleviate pathological changes in diabetic mice and reduce the levels of IL-1 and IL-6. Notably, Sanghuang polysaccharides can also effectively alleviate hyperglycemic symptoms in rats with type 2 diabetes mellitus (T2DM). Numerous studies have shown that Phellinus linteus polysaccharide has a certain therapeutic effect on diabetes.

[0026] Poria cocos, scientifically known as Poria, is the dried sclerotium of the fungus Poria cocos (Schw.)wolf, belonging to the Polyporaceae family. Poria cocos is sweet and bland in taste, neutral in nature, and enters the heart, lung, spleen, and kidney meridians. It has the effects of promoting diuresis and eliminating dampness, strengthening the spleen, and calming the mind and spirit. The *Shennong Bencao Jing* (Shennong's Classic of Materia Medica) records that it "treats chest and rib pain, melancholy, fright, palpitations, epigastric pain, chills and fever, cough, dry mouth and tongue, and promotes urination. Long-term use calms the spirit, nourishes the mind, reduces hunger, and prolongs life." Pharmacologically, Poria cocos has various effects, including regulating immunity, promoting diuresis, reducing swelling, lowering proteinuria, improving kidney function, anti-inflammation, and anti-renal fibrosis. It is especially suitable for kidney protection and patients with diabetic nephropathy. Studies have shown that Poria cocos and its surface layer can exert a nephroprotective effect through multiple molecular mechanisms, including TGF-β1 / Smad, Wnt / β-catenin, IκB / NF-κB and Keap1 / Nrf2 pathways, thereby effectively improving diabetic nephropathy.

[0027] Yam, scientifically known as *Dioscorea rhizoma*, is the dried rhizome of *Dioscorea opposita* Thunb., a plant in the Dioscoreaceae family. Yam is sweet and neutral in nature, and enters the spleen, lung, and kidney meridians; it has the effects of invigorating qi and nourishing yin, tonifying the spleen, lungs, and kidneys, and astringing essence and stopping leukorrhea. The *Shennong Bencao Jing* (Shennong's Classic of Materia Medica) lists yam as a superior herb, recording that it "treats internal injuries, replenishes deficiency, eliminates cold and heat pathogens, invigorates the middle jiao and strengthens qi, builds muscle, and with prolonged use, sharpens hearing and vision." The *Bencao Gangmu* (Compendium of Materia Medica) also considers yam to "benefit kidney qi and strengthen the spleen and stomach," highlighting its significant effects in tonifying the spleen and stomach, and astringing essence. Modern pharmacological research further shows that yam has multiple effects, including regulating gastrointestinal function, lowering blood sugar, enhancing immunity, delaying aging, reducing proteinuria, and improving kidney function. It can effectively control blood sugar levels in diabetic patients and protect kidney function. Studies have also shown that yam polysaccharides can significantly improve blood sugar, creatinine, blood urea nitrogen, and kidney pathological damage in alloxan-induced diabetic nephropathy mice. In addition, formulas with yam as the main ingredient can improve various pathological changes in chronic renal failure. For example, Liuwei Dihuang Decoction can inhibit and reduce renal interstitial fibrosis of renal tubular epithelial cells, thereby reducing and delaying the process of renal fibrosis and protecting kidney function.

[0028] Coptis chinensis, scientifically known as *Coptidis Rhizoma*, is the dried rhizome of *Coptis chinensis* Franch., *Coptis deltoidea* CYCheng et Hsiao, or *Coptis teeta* Wall., all belonging to the Ranunculaceae family. The *Changsha Yaoxie* records that Coptis chinensis is "bitter and cold in nature, entering the Hand Shaoyin Heart Meridian. It clears heat from the heart, reduces fever, drains fire, and relieves irritability." Coptis chinensis is bitter and cold in nature, and enters the Heart, Spleen, Liver, Stomach, Gallbladder, and Large Intestine Meridians. It has the effects of clearing heat and drying dampness, draining fire, and detoxifying. Due to its blood sugar-lowering effect, Coptis chinensis can be used to treat diabetes and its complications. Studies on the mechanism of action of Coptis chinensis have found that its active ingredients can significantly increase serum glutathione levels in diabetic rat models, enhance the body's antioxidant capacity, and protect vascular endothelial cells. In addition, Coptis chinensis can increase endogenous insulin secretion, improve the body's sensitivity to insulin, and thus reduce insulin resistance. Multiple studies have shown that berberine extracted from the rhizome of Coptis chinensis can significantly improve various clinical symptoms in diabetic patients and help delay the onset of diabetic complications.

[0029] In summary, this formula, through its multiple effects of tonifying the liver and kidneys, clearing heat and promoting body fluid production, and invigorating blood circulation, combined with the pharmacological effects of each herb, aims to achieve the effects of lowering blood sugar, protecting the kidneys, and delaying aging. Based on traditional Chinese medicine theory and combined with modern pharmacological research, this formula provides a comprehensive treatment plan for patients with diabetes and DKD.

[0030] Compared with the prior art, the advantages of this invention are:

[0031] (1) The raw materials in the traditional Chinese medicine composition formula for lowering blood sugar, protecting the kidneys, and anti-aging provided by this invention are all traditional Chinese medicines that are both food and medicine. In the safety experiment, the LD50 was... 50 The concentration of >5000 mg / kg indicates that the traditional Chinese medicine composition has good safety.

[0032] (2) The traditional Chinese medicine composition for lowering blood sugar, protecting the kidneys, and anti-aging provided by the present invention has a significant protective effect against diabetic kidney damage induced by STZ combined with a high-sugar and high-fat diet.

[0033] (3) This invention utilizes a combination of Rehmannia glutinosa extract, Cornus officinalis extract, Camellia sinensis extract, Polygonatum sibiricum extract, Phellinus linteus extract, Poria cocos extract, Dioscorea opposita extract, and Coptis chinensis extract to effectively reduce fasting blood glucose, insulin, and glycated serum protein levels, thereby achieving a hypoglycemic effect. Simultaneously, this composition can also reduce renal index, serum creatinine, blood urea nitrogen, and 24-hour urinary protein levels, significantly improving diabetic nephropathy. Furthermore, it can effectively reduce cholesterol, triglycerides, and low-density lipoprotein levels while increasing high-density lipoprotein levels, thereby improving lipid metabolism disorders caused by diabetic nephropathy.

[0034] (4) The present invention achieves the therapeutic effect of anti-diabetic nephropathy by scientifically combining Rehmannia glutinosa extract, Cornus officinalis extract, vine tea extract, Polygonatum sibiricum extract, Phellinus linteus extract, Poria cocos extract, Dioscorea opposita extract and Coptis chinensis extract. Attached Figure Description

[0035] Figure 1 This is a graph showing the levels of fasting blood glucose, insulin, and glycated hemoglobin in the serum of mice in each group of the pharmacodynamic experiments of this invention.

[0036] Figure 2 The graph shows the renal index, serum creatinine, serum urea nitrogen, and 24-hour urinary protein levels of mice in each group of the pharmacodynamic experiment of this invention.

[0037] Figure 3 This is a graph showing the serum cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein levels of mice in each group during the pharmacodynamic experiment of this invention.

[0038] Figure 4 This is a schematic diagram showing the HE staining, Masson staining, and PAS staining results of mouse kidney tissue in each group of the pharmacodynamic experiments of this invention. Detailed Implementation

[0039] Example 1: Formulation into tablets

[0040] Mix 3 parts Rehmannia glutinosa extract, 2 parts Cornus officinalis extract, 3 parts Camellia sinensis extract, 3 parts Polygonatum sibiricum extract, 3 parts Phellinus linteus extract, 3 parts Poria cocos extract, 5 parts Dioscorea opposita extract and 1 part Coptis chinensis extract, then add starch and carboxymethyl cellulose, mix evenly, granulate, compress, coat, and make into tablets.

[0041] Example 2: Formulation into tablets

[0042] Mix 4 parts Rehmannia glutinosa extract, 2 parts Cornus officinalis extract, 3 parts Camellia sinensis extract, 3 parts Polygonatum sibiricum extract, 3 parts Phellinus linteus extract, 3 parts Poria cocos extract, 5 parts Dioscorea opposita extract and 1 part Coptis chinensis extract, then add starch and carboxymethyl cellulose, mix evenly, granulate, compress, coat, and make into tablets.

[0043] Example 3: Formulation into tablets

[0044] Mix 4 parts Rehmannia glutinosa extract, 3 parts Cornus officinalis extract, 3 parts Camellia sinensis extract, 3 parts Polygonatum sibiricum extract, 3 parts Phellinus linteus extract, 3 parts Poria cocos extract, 5 parts Dioscorea opposita extract and 1 part Coptis chinensis extract, then add starch and carboxymethyl cellulose, mix evenly, granulate, compress, coat, and make into tablets.

[0045] Example 4: Forming tablets

[0046] Mix 4 parts Rehmannia glutinosa extract, 3 parts Cornus officinalis extract, 4 parts Camellia sinensis extract, 3 parts Polygonatum sibiricum extract, 3 parts Phellinus linteus extract, 3 parts Poria cocos extract, 5 parts Dioscorea opposita extract and 1 part Coptis chinensis extract, then add starch and carboxymethyl cellulose, mix evenly, granulate, compress, coat, and make into tablets.

[0047] Example 5: Formulation into tablets

[0048] Mix 4 parts Rehmannia glutinosa extract, 3 parts Cornus officinalis extract, 4 parts Camellia sinensis extract, 4 parts Polygonatum sibiricum extract, 4 parts Phellinus linteus extract, 4 parts Poria cocos extract, 5 parts Dioscorea opposita extract and 1 part Coptis chinensis extract, then add starch and carboxymethyl cellulose, mix evenly, granulate, compress, coat, and make into tablets.

[0049] Example 6: Formulation of hard capsules

[0050] Three parts of Rehmannia glutinosa extract, two parts of Cornus officinalis extract, three parts of Camellia sinensis extract, three parts of Polygonatum sibiricum extract, three parts of Phellinus linteus extract, three parts of Poria cocos extract, five parts of Dioscorea opposita extract, and one part of Coptis chinensis extract were mixed evenly, pulverized, and passed through a No. 3 sieve to form granules. The granules were then dried at 70–90°C. After drying, the granules were sized to ensure uniformity and consistency. Finally, the sized granules were filled into gelatin hard capsules to form hard capsules, each containing 0.5g of product.

[0051] Example 7: Formulation of hard capsules

[0052] Four parts of Rehmannia glutinosa extract, two parts of Cornus officinalis extract, three parts of Camellia sinensis extract, three parts of Polygonatum sibiricum extract, three parts of Phellinus linteus extract, three parts of Poria cocos extract, five parts of Dioscorea opposita extract, and one part of Coptis chinensis extract were mixed evenly, pulverized, and passed through a No. 3 sieve to form granules. The granules were then dried at 70–90°C. After drying, the granules were sized to ensure uniformity and consistency. Finally, the sized granules were filled into gelatin hard capsules to form hard capsules, each containing 0.5g of contents.

[0053] Example 8: Formulation of hard capsules

[0054] Four parts of Rehmannia glutinosa extract, three parts of Cornus officinalis extract, three parts of Camellia sinensis extract, three parts of Polygonatum sibiricum extract, three parts of Phellinus linteus extract, three parts of Poria cocos extract, five parts of Dioscorea opposita extract, and one part of Coptis chinensis extract were mixed evenly, pulverized, and passed through a No. 3 sieve to form granules. The granules were then dried at 70–90°C. After drying, the granules were sized to ensure uniformity and consistency. Finally, the sized granules were filled into gelatin hard capsules to form hard capsules, each containing 0.5g of contents.

[0055] Experimental example:

[0056] The formula of this invention is named Antang Yishen Formula, and a series of safety and efficacy experiments have been conducted (the formula is based on the proportion of the traditional Chinese medicine composition in Example 6). The results are as follows:

[0057] 1. Safety Experiment

[0058] Objective: To observe the activity and mortality of mice after administration of the test product and to determine the safety of the formulation.

[0059] Test sample: Antang Yishenfang dry extract (Antang Yishenfang), which lowers blood sugar, protects the kidneys, and has anti-aging properties.

[0060] Methods: The clinical adult dosage of this Antang Yishen formula is 72g / 60kg = 1.2g / kg of raw drug, which is converted to a mouse dosage of 1.2g / kg * 12.3 = 14.76g / kg of raw drug. (Where 12.3 is the conversion factor between human and mouse dosage; the actual dosage will depend on specific experimental data.)

[0061] At room temperature, the water extract of 216g of medicinal material was refined into freeze-dried product, yielding 51.2g of extract which was then powdered. The yield was 51.2g / 216g*100%=23.7%, and each gram of extract powder was equivalent to 216g / 51.2g=4.22g of raw medicinal material.

[0062] Weigh 20g of the extract powder, dissolve it in distilled water, and bring the volume to 30mL (0.667g / mL). Mice were administered the extract orally (ig) 16 hours after fasting, at 4-hour intervals, with a dose of 0.15mL / 10g*bw (bw being body weight) given four times, for a total dose of 60mL / kg. This means the daily dose of extract for mice was 0.667g / mL * 60mL / kg = 40g / kg. Mice were then observed for 14 consecutive days, and their activity and mortality were recorded in detail after gavage to determine the safety of the formulation.

[0063] Results: After each administration of the test product, the mice exhibited normal activity, and no deaths or other abnormalities occurred after gavage. Furthermore, after 14 consecutive days of observation, no mouse deaths or other abnormalities were observed, and the mice continued to gain weight. Therefore, the maximum tolerated dose (MTD) of the test product (extract) orally administered to mice within 24 hours is 40 g / kg. This dose is equivalent to 40 * 4.22 = 168.8 g / kg of the original medicinal material.

[0064] Conclusion: No animals died in the acute oral toxicity test, and the LD50 of the test substance was within acceptable limits. 50 For concentrations exceeding 5000 mg / kg (5 g / kg), the toxicity classification is practically non-toxic. (Actual dosage depends on the specific experimental quantity.)

[0065] 2. Pharmacodynamic experiments:

[0066] Experimental Design: Fifty male SD rats aged 4-6 weeks were selected. After acclimatization to a standard diet for one week, 10 rats were randomly selected as the standard diet group (control group), while the remaining rats were fed a high-fat diet for 6 weeks. After 6 weeks, the rats were fasted for 12 hours and then injected intraperitoneally with 3% streptozotocin (STZ). After continuing to be fed for 2 weeks, 24-hour metabolic monitoring was performed, and urine was collected to detect the levels of urinary glucose, total urinary protein, and microalbumin.

[0067] Model screening: Diabetic rats meeting the following criteria were selected as diabetic nephropathy models: blood glucose levels ≥16.7 mmol / L three times within two weeks, positive urine glucose, urine volume >50% of the control group, and total urine protein and microalbumin >100% of the control group.

[0068] Grouping and intervention: The rats that met the criteria were then divided into four groups: Model group (equivalent dose of ddH2O, ig), Metformin group (180 mg / kg / d, ig), low-dose AnTang YiShen Fang group (ATYS-L, AnTang YiShen Fang dosage of 3.5 g / kg / d, ig), and high-dose AnTang YiShen Fang group (ATYS-H, AnTang YiShen Fang dosage of 7 g / kg / d, ig), and the intervention lasted for 5 weeks.

[0069] Sample Collection and Detection: Urine samples were collected from rats using metabolic cages 24 hours before sacrifice. After the experiment, rats were fasted for 12 hours, and blood was then collected via orbital sampling. Fasting blood glucose levels were measured using a glucometer. Subsequently, serum levels of glycated serum protein (GSP), blood urea nitrogen (BUN), serum creatinine (Scr), 24-hour urinary protein (24hUP), total cholesterol (T-CHO), triglycerides (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured using an automated biochemical analyzer. In addition, serum insulin levels were detected using a kit. Finally, kidney tissue was separated, prepared for pathological sections, and stained with hematoxylin and eosin (HE). All results were statistically analyzed using GraphPad software and subjected to one-way ANOVA. Data are expressed as mean ± standard deviation (x ± s).

[0070] Result: As Figures 1-3As shown, under the premise of successful DKD modeling, compared with the control group, the model group showed significantly increased levels of renal index, fasting blood glucose, insulin, GSP, Scr, BUN, 24h UP, T-CHO, TC, and LDL-C, while significantly decreased levels of HDL-C. Notably, both the high-dose and low-dose Antang Yishenfang groups were superior to the model group in all the above indicators. Specifically, the renal index, insulin, fasting blood glucose, GSP, Scr, BUN, 24h UP, T-CHO, TC, and LDL-C levels were significantly lower in the model group, while the HDL-C level was significantly higher, and this improvement effect showed a dose-dependent relationship. Furthermore, the high-dose and low-dose Antang Yishenfang groups and the positive control drug Met group all showed significantly reduced levels of Scr, BUN, 24h UP, and LDL-C. These results indicate that high-dose and low-dose Antang Yishenfang can significantly improve renal function abnormalities in DKD model rats, thereby effectively delaying the progression of CKD.

[0071] like Figure 4 As shown, H&E staining revealed that, compared with the control group, the DKD model group rats exhibited glomerular hypertrophy, basement membrane thickening, increased mesangial matrix, and tubular vacuolation. However, the high-dose and low-dose Antang Yishenfang groups significantly improved these pathological abnormalities. Masson staining further confirmed that the DKD model group rats showed significant glomerular and interstitial fibrosis, while the high-dose and low-dose Antang Yishenfang groups significantly reduced the level of glomerular and interstitial fibrosis. PAS staining showed that the glomerular basement membrane of the DKD model group rats was thickened, while the thickening of the glomerular basement membrane of the rats in the high-dose and low-dose Antang Yishenfang groups was significantly improved. The above pathological results indicate that both high-dose and low-dose Antang Yishenfang groups can significantly improve glomerular and tubular damage, basement membrane thickening, and fibrosis in DKD rats, and most pathological indicators are superior to those of the positive control drug Met group. In summary, the Antang Yishen Formula of the present invention can not only reduce blood sugar levels in DKD, but also significantly improve renal function abnormalities, glomerular basement membrane thickening, mesangial matrix increase and fibrosis, thereby delaying the progression of chronic kidney disease (CKD).

Claims

1. A traditional Chinese medicine composition for treating diabetic nephropathy, characterized in that, The formula consists of the following components in the indicated weight proportions: 3-4 parts Rehmannia glutinosa extract, 2-3 parts Cornus officinalis extract, 3-4 parts Camellia sinensis extract, 3-4 parts Polygonatum sibiricum extract, 3-4 parts Phellinus linteus extract, 3-4 parts Poria cocos extract, 3-5 parts Dioscorea opposita extract, and 1 part Coptis chinensis extract.

2. The method for preparing a traditional Chinese medicine composition for treating diabetic nephropathy according to claim 1, characterized in that, The process includes the following steps: First, extracts of Rehmannia glutinosa, Cornus officinalis, vine tea, Polygonatum sibiricum, Phellinus linteus, Poria cocos, Dioscorea opposita, and Coptis chinensis from the traditional Chinese medicine composition are obtained through the following method: (1) Crush the raw Rehmannia root, add 6 to 10 times the amount of water and decoct 2 to 3 times, 1 hour each time. Remove the residue and combine the decoction with the filtrate. Concentrate the filtrate under reduced pressure at 70 to 90 °C to obtain the extract. Freeze-dry the extract under vacuum and pulverize it through a No. 6 sieve to obtain the raw Rehmannia root extract powder. (2) Crush the Cornus officinalis, add 6 to 10 times the amount of water and decoct 2 to 3 times, 1 hour each time. Remove the residue and combine the decoction with the filtrate. Concentrate the filtrate under reduced pressure at 70 to 90 °C to obtain an extract. Freeze-dry the extract under vacuum and pulverize it through a No. 6 sieve to obtain Cornus officinalis extract powder. (3) Add 6 to 10 times the amount of water to the vine tea and decoct 2 to 3 times, 1 hour each time. Remove the residue and combine the decoction with the filtrate. Concentrate the filtrate under reduced pressure at 70 to 90°C to obtain an extract. Freeze-dry the extract under vacuum and pulverize it through a No. 6 sieve to obtain vine tea extract powder. (4) Add 6 to 10 times the amount of water to the Polygonatum and decoct 1 to 2 times, 1 hour each time. Remove the residue and combine the decoction with the filtrate. Concentrate the filtrate under reduced pressure at 70 to 90°C to obtain the extract. Freeze-dry the extract under vacuum and pulverize it through a No. 6 sieve to obtain Polygonatum extract powder. (5) Add 6 to 10 times the amount of water to decoct 2 to 3 times, 1 hour each time, remove the residue and take the decoction and combine the filtrate. Concentrate the filtrate under reduced pressure at 70 to 90°C to obtain the extract. Freeze-dry the extract under vacuum, pulverize it and pass it through a No. 6 sieve to obtain the Sanghuang extract powder. (6) Add 6 to 10 times the amount of water to Poria cocos and decoct 2 to 3 times, 1 hour each time. Remove the residue and combine the decoction with the filtrate. Concentrate the filtrate under reduced pressure at 70 to 90°C to obtain an extract. Freeze-dry the extract under vacuum and pulverize it through a No. 6 sieve to obtain Poria cocos extract powder. (7) Add 6 to 10 times the amount of water to the yam and decoct 2 to 3 times, 1 hour each time. Remove the residue and combine the decoction with the filtrate. Concentrate the filtrate under reduced pressure at 70 to 90°C to obtain an extract. Freeze-dry the extract under vacuum and pulverize it through a No. 6 sieve to obtain yam extract powder. (8) Add 5 to 10 times the amount of water to Coptis chinensis and decoct 2 to 3 times, 1 hour each time. Remove the residue and combine the decoction with the filtrate. Concentrate the filtrate under reduced pressure at 70 to 90°C to obtain an extract. Freeze-dry the extract under vacuum and pulverize it through a No. 6 sieve to obtain Coptis chinensis extract powder. Finally, the powdered extracts of the following eight herbs—Rehmannia glutinosa, Cornus officinalis, vine tea, Polygonatum sibiricum, Phellinus linteus, Poria cocos, Dioscorea opposita, and Coptis chinensis—are mixed in a certain proportion.

3. The traditional Chinese medicine composition preparation for treating diabetic nephropathy according to claim 1, characterized in that: The traditional Chinese medicine composition preparation includes the traditional Chinese medicine composition as described in claim 1.

4. The traditional Chinese medicine composition preparation for treating diabetic nephropathy according to claim 3, characterized in that: The traditional Chinese medicine composition preparation is in the form of tablets, powders, granules, powders, capsules, ointments, pills, or liquid preparations.

5. A traditional Chinese medicine composition preparation for treating diabetic nephropathy according to claim 3, characterized in that: The traditional Chinese medicine composition preparation also includes food additives.

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