Traditional Chinese medicine composition for treating diabetic nephropathy, pharmaceutical preparation and preparation method thereof

Abstract

The invention provides a traditional Chinese medicine composition for treating diabetic nephropathy, a pharmaceutical preparation and a preparation method thereof, and belongs to the technical field of medicines. The traditional Chinese medicine composition comprises the following components: astragalus membranaceus, codonopsis pilosula, cassia twig, cistanche, dogwood, semen cuscutae, bighead atractylodes rhizome, rhizoma atractylodis, pericarpium citri reticulatae, poria cocos, rhizoma alismatis, yam rhizome, corydalis tuber and caulis spatholobi. The traditional Chinese medicine composition and the pharmaceutical preparation provided by the invention have the effects of invigorating spleen and tonifying kidney, warming phlegm and fluid retention, and promoting blood circulation and promoting coronary circulation, and have a good treatment effect on diabetic nephropathy.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a traditional Chinese medicine composition, pharmaceutical preparation and preparation method for treating diabetic nephropathy. Background Technology

[0002] Diabetic kidney disease (DKD) is a chronic kidney disease (CKD) caused by diabetes. It is the most common complication of diabetes, and 30-40% of diabetic patients will develop DKD. It is also a common type of CKD.

[0003] Early diabetic nephropathy (DKD) primarily manifests as increased microalbuminuria with a lack of typical symptoms. Over time, it can progress to overt proteinuria, edema, hypertension, and impaired kidney function, eventually leading to end-stage renal failure. The prevalence of type 2 diabetes mellitus (T2DM) combined with chronic kidney disease (CKD) is approximately 36%. In middle-aged and elderly individuals, DKD has become the leading cause of end-stage renal disease (ESRD). DKD has an insidious onset, and once it enters the stage of massive proteinuria, it progresses to ESRD at approximately 14 times the rate of other kidney diseases. Furthermore, patients with DKD who also have diabetes have a higher mortality rate compared to those without.

[0004] Currently, there is no ideal drug for treating DKD. Modern medical treatment for DKD mainly includes: lifestyle interventions, control of risk factors (hyperglycemia, hypertension, lipid metabolism disorders, etc.), diabetes education, treatment of complications of renal insufficiency, and dialysis, in order to reduce or delay the occurrence of massive proteinuria and prevent or delay the progression of kidney disease. Lifestyle interventions include reasonable weight control, a healthy diet, smoking cessation, and appropriate exercise; nutritional interventions mainly include restriction of protein and sodium. When choosing hypoglycemic drugs for DKD patients, drugs with cardio- and renal benefits are preferred, such as sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA).

[0005] Traditional Chinese medicine (TCM) has certain advantages in improving clinical symptoms, reducing proteinuria levels, and slowing the progression of diabetic nephropathy. Based on the principle of combining disease and syndrome differentiation, this disease falls under the TCM categories of "edema," "asthenia," and "obstruction" secondary to diabetes mellitus. Previous theories held that the basic pathogenesis of diabetic nephropathy in TCM was yin deficiency and dryness-heat. However, with the gradual development of TCM, simple yin deficiency and dryness-heat is no longer sufficient to explain the pathogenesis of obese DKD, and TCM experts have gained new insights into the pathogenesis of diabetic nephropathy. The *Treatise on the Spleen and Stomach* states, "All diseases arise from the decline of the spleen and stomach," illustrating that most diseases are caused by spleen and stomach deficiency. Spleen and stomach deficiency leads to impaired digestion and absorption, resulting in the internal generation of phlegm and dampness, which accumulates and leads to obesity. The *Correct Transmission of Medicine* states, "Thick and sticky body fluids become phlegm and fluid retention; over time, they seep into the vessels, making the blood turbid," suggesting that dampness transforms body fluids into phlegm and fluid retention, and enters the blood, obstructing blood flow and causing blood turbidity. Therefore, the pathogenesis of obese DKD is characterized by deficiency of the root and excess of the branch, with the excess manifesting as the accumulation of phlegm-dampness, phlegm-turbidity, and phlegm-blood stasis in the body. The root deficiency is primarily spleen deficiency, which is the initial cause of obese DKD. The disease mainly affects the spleen and stomach; spleen deficiency leads to impaired transportation and transformation, resulting in the accumulation of dampness and turbidity, causing obesity and a white, greasy tongue coating. Retention of dampness obstructs the flow of Qi, leading to abdominal distension. Dampness also affects the blood, hindering the circulation of Qi and blood, causing blood stasis in the limbs, resulting in numbness, as stated in the *Treatise on Febrile and Miscellaneous Diseases*: "When the spleen Qi fails to circulate, the stomach becomes turbid. When the Ying and Wei Qi are obstructed, the blood congeals and does not flow." Furthermore, kidney Qi deficiency, spleen deficiency, and kidney inability to transform and transport lead to the retention of phlegm and turbidity. Symptoms include heaviness and dizziness in the head, obesity, weakness in the lower back and knees, numbness in the limbs, purplish-dark lips and tongue, pale and swollen tongue with teeth marks, petechiae, or ecchymosis, thick or greasy tongue coating, wiry and slippery or soft and hesitant pulse, and may be accompanied by dizziness, confusion, forgetfulness, sluggishness, chest tightness, heart pain, palpitations, anxiety, or cough with shortness of breath and thick yellow-white phlegm. Therefore, in treatment, traditional Chinese medicine experts adopt a combined approach of addressing both the symptoms and the root cause of diabetic nephropathy. They prescribe medication based on the primary pathogenesis of spleen and kidney qi deficiency combined with phlegm-dampness stagnation, emphasizing both symptomatic and root-cause treatment, and often simultaneously employing methods to strengthen the body's resistance and consolidate its foundation. Summary of the Invention

[0006] To address the shortcomings of existing technologies, the present invention aims to provide a traditional Chinese medicine composition, pharmaceutical preparation, and preparation method for treating diabetic nephropathy. This traditional Chinese medicine composition and pharmaceutical preparation have the effects of strengthening the spleen and kidneys, warming and resolving phlegm, and promoting blood circulation, thus exhibiting good therapeutic effects on diabetic nephropathy.

[0007] To achieve this objective, the present invention adopts the following technical solution:

[0008] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating diabetic nephropathy, the traditional Chinese medicine composition comprising the following components:

[0009] Astragalus, Codonopsis, Cinnamon Twig, Cistanche, Cornus, Cuscuta, Atractylodes Macrocephala, Atractylodes Rhizome, Tangerine Peel, Poria, Alisma Rhizome, Dioscorea Rhizome, Corydalis Rhizome, and Spatholobus Stem.

[0010] In some preferred embodiments of the present invention, the traditional Chinese medicine composition comprises the following components in parts by weight:

[0011] Astragalus membranaceus 5-15 parts, Codonopsis pilosula 3-9 parts, Cinnamomum cassia 4-12 parts, Cistanche deserticola 3-9 parts, Cornus officinalis 4-12 parts, Cuscuta chinensis 4-12 parts, Atractylodes macrocephala 4-12 parts, Atractylodes lancea 3-9 parts, Citrus reticulata 4-12 parts, Poria cocos 3-9 parts, Alisma plantago-aquatica 2.5-7.5 parts, Dioscorea hypoglauca 3-9 parts, Corydalis yanhusuo 3-9 parts, and Spatholobus suberectus 2.5-7.5 parts.

[0012] The weight of Astragalus membranaceus can be any value within the range of 5-15 parts, such as 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, 10 parts, 10.5 parts, 11 parts, 11.5 parts, 12 parts, 12.5 parts, 13 parts, 13.5 parts, 14 parts, 14.5 parts, or 15 parts, etc.

[0013] The weight of Codonopsis pilosula can be any value within the range of 3-9 parts, such as 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, or 9 parts, etc.

[0014] The weight of cinnamon twigs can be any value within the range of 4-12 parts, such as 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, 10 parts, 10.5 parts, 11 parts, 11.5 parts, or 12 parts, etc.

[0015] The weight of Cistanche deserticola can be any value within the range of 3-9 parts, such as 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, or 9 parts, etc.

[0016] The weight of Cornus officinalis can be any value within the range of 4-12 parts, such as 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, 10 parts, 10.5 parts, 11 parts, 11.5 parts, or 12 parts, etc.

[0017] The weight of dodder seeds can be any value within the range of 4-12 parts, such as 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, 10 parts, 10.5 parts, 11 parts, 11.5 parts, or 12 parts, etc.

[0018] The weight of Atractylodes macrocephala can be any value within the range of 4-12 parts, such as 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, 10 parts, 10.5 parts, 11 parts, 11.5 parts, or 12 parts, etc.

[0019] The weight of Atractylodes lancea can be any value within the range of 3-9 parts, such as 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, or 9 parts, etc.

[0020] The weight of dried tangerine peel can be any value within the range of 4-12 parts, such as 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, 10 parts, 10.5 parts, 11 parts, 11.5 parts, or 12 parts, etc.

[0021] The weight of Poria cocos can be any value within the range of 3-9 parts, such as 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, or 9 parts, etc.

[0022] The weight of Alisma plantago-aquatica can be any value in the range of 2.5-7.5 parts, such as 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts or 7.5 parts, etc.

[0023] The weight of Dioscorea hypoglauca can be any value in the range of 3 to 9 parts, such as 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, or 9 parts, etc.

[0024] The weight of Corydalis can be any value within the range of 3-9 parts, such as 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, or 9 parts, etc.

[0025] The weight of chicken blood vine can be any value within the range of 2.5-7.5 parts, such as 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts or 7.5 parts, etc.

[0026] In some preferred embodiments of the present invention, the traditional Chinese medicine composition comprises the following components in parts by weight:

[0027] Astragalus membranaceus 8-12 parts, Codonopsis pilosula 4.5-7.5 parts, Cinnamomum cassia 6-10 parts, Cistanche deserticola 4.5-7.5 parts, Cornus officinalis 6-10 parts, Cuscuta chinensis 6-10 parts, Atractylodes macrocephala 6-10 parts, Atractylodes lancea 4.5-7.5 parts, Citrus reticulata 6-10 parts, Poria cocos 4.5-7.5 parts, Alisma plantago-aquatica 4-6 parts, Dioscorea hypoglauca 4.5-7.5 parts, Corydalis yanhusuo 4.5-7.5 parts, and Spatholobus suberectus 4-6 parts.

[0028] In some preferred embodiments of the present invention, the traditional Chinese medicine composition comprises the following components in parts by weight:

[0029] Astragalus membranaceus 10 parts, Codonopsis pilosula 6 parts, Cinnamomum cassia 8 parts, Cistanche deserticola 6 parts, Cornus officinalis 8 parts, Cuscuta chinensis 8 parts, Atractylodes macrocephala 8 parts, Atractylodes lancea 6 parts, Citrus reticulata 8 parts, Poria cocos 6 parts, Alisma plantago-aquatica 5 parts, Dioscorea hypoglauca 6 parts, Corydalis yanhusuo 6 parts, and Spatholobus suberectus 5 parts.

[0030] Traditional Chinese Medicine (TCM) diagnosis of diabetic nephropathy: Spleen and Kidney Qi Deficiency, Phlegm-Dampness Stagnation. Symptoms include frequent and clear urination, sometimes cloudy urine, fatigue, shortness of breath, reluctance to speak, poor appetite, abdominal distension, edema, loose stools, chest tightness, epigastric fullness, distending pain or stabbing pain, heaviness in the head and body, fatigue and drowsiness, or swelling, hardening, and numbness of the skin, pale purple tongue or spotted tongue, slippery tongue coating, and wiry and hesitant pulse.

[0031] Diabetic nephropathy (DKD) diagnosis in Western medicine: Patients must meet the ADA 2020 diagnostic criteria for diabetes mellitus (DM), have a clear history of DM, and have a causal relationship with changes in urinary protein and renal function. Other primary and secondary glomerular diseases and systemic diseases must be excluded. One of the following conditions must be met for a diagnosis of DKD.

[0032] 1. Random urine albumin / creatinine ratio (UACR) ≥30mg / g or urine albumin excretion rate (UAER) ≥30mg / 24h, and UACR or UAER is repeated within 3-6 months, with 2 out of 3 times reaching or exceeding the threshold value; other interfering factors such as infection are excluded;

[0033] 2. Estimated glomerular filtration rate (eGFR) < 60 mL / min -1 ·(1.73m 2 ) -1 More than 3 months;

[0034] 3. The kidney biopsy showed pathological changes consistent with DKD.

[0035] This invention utilizes the scientific formulation of the aforementioned traditional Chinese medicine components to obtain a traditional Chinese medicine composition with good therapeutic effects on diabetic nephropathy. The formulation mechanism of this traditional Chinese medicine composition is as follows:

[0036] This formula follows the principle of "tonifying deficiency and unblocking stagnation," taking the strengthening of the spleen and kidneys as the primary treatment, supplemented by methods of warming and transforming dampness and turbidity, and promoting blood circulation and unblocking the meridians. The formula is well-composed and the layers are well-organized.

[0037] The formula is based on the principal herbs Astragalus membranaceus, Codonopsis pilosula, and Cuscuta chinensis: Astragalus membranaceus, sweet and warm, enters the lung and spleen meridians, excelling at tonifying qi, raising yang, and relieving stagnation and numbness, making it the chief herb for tonifying qi; Codonopsis pilosula, sweet and neutral, enters the spleen and lung meridians, specifically focusing on strengthening the spleen and lungs to consolidate acquired constitution; Cuscuta chinensis, pungent and sweet, enters the liver, kidney, and spleen meridians, tonifying the liver and kidneys, consolidating essence and replenishing marrow to nourish innate constitution. The combination of these three herbs tonifies both the spleen and kidneys, perfectly aligning with the principle of "treating both innate and acquired constitutions," laying the foundation for strengthening the body's resistance and consolidating its foundation.

[0038] The assistant herbs are cinnamon twig, atractylodes macrocephala, cistanche deserticola, and cornus officinalis. Cinnamon twig is pungent, sweet, and warm, entering the heart, lung, and bladder meridians. It warms the meridians, unblocks the vessels, assists yang in transforming qi, and promotes the circulation of qi and blood. Atractylodes macrocephala strengthens the spleen and dries dampness, specifically treating spleen deficiency with dampness retention. Cistanche deserticola warms the kidneys and replenishes essence, effectively tonifying the fire of the gate of life. Cornus officinalis tonifies the liver and kidneys, astringes and consolidates, and is used for enuresis and frequent urination. The four herbs together assist the principal herb in warming and tonifying the spleen and kidneys, while also promoting yang and transforming qi, ensuring that the tonification is not stagnant and the warming is not drying.

[0039] The adjuvant herbs are Atractylodes lancea, Citrus reticulata peel, Poria cocos, Dioscorea hypoglauca, and Corydalis yanhusuo: Atractylodes lancea, Citrus reticulata peel, and Poria cocos work together to strengthen the spleen and dry dampness, while Citrus reticulata peel can also resolve phlegm; Dioscorea hypoglauca promotes diuresis, removes turbidity, dispels wind and relieves numbness, and is good at removing chyluria, leukorrhea, and joint pain; Corydalis yanhusuo enters the blood aspect of the liver and spleen meridians, invigorates blood circulation, promotes qi circulation, and relieves pain, specifically addressing symptoms of stagnation and pain. The five herbs work synergistically to assist the principal and assistant herbs in tonifying deficiency, while also removing dampness and turbidity and clearing stagnation, addressing both the root cause and the symptoms.

[0040] The guiding herbs are Alisma plantago-aquatica and Spatholobus suberectus: Alisma plantago-aquatica enters the kidney and bladder, promotes diuresis and eliminates dampness, guides turbidity downward, and expels dampness through urination; Spatholobus suberectus enters the liver and kidney meridians, invigorates blood and nourishes blood, relaxes muscles and tendons, improves numbness and swelling of the limbs and joints, and also guides the other herbs, directing their medicinal effects directly to the affected area.

[0041] The formula is meticulously formulated, combining supportive and pathogenic factors: Astragalus and Codonopsis are used to tonify Qi, while Cinnamon Twig and Spatholobus Stem are used to warm and unblock the flow of Qi. Atractylodes Macrocephala and Atractylodes Rhizome, along with Poria, are used to eliminate dampness, and Corydalis Rhizome and Spatholobus Stem are used to invigorate blood circulation. Together, they strengthen the spleen and kidneys, warm and transform dampness, and invigorate blood circulation, thus restoring normal function of the spleen and kidneys, resolving dampness, and promoting the smooth flow of Qi and blood, thereby alleviating various symptoms.

[0042] The traditional Chinese medicine composition provided by this invention has the following functions and indications: strengthening the spleen and kidneys, warming and resolving phlegm and dampness, and promoting blood circulation and unblocking the meridians. It is used for spleen and kidney qi deficiency, phlegm and dampness stagnation syndrome, with symptoms such as frequent and clear urination, sometimes cloudy urine, fatigue, shortness of breath, reluctance to speak, poor appetite, abdominal distension, edema, loose stools, chest tightness, epigastric fullness, distending pain or stabbing pain, heaviness in the head and body, fatigue and drowsiness, or swollen and numb skin, pale purple tongue or spotted tongue, slippery tongue coating, and wiry and hesitant pulse. It is also used for diabetic nephropathy with the above symptoms.

[0043] In a second aspect, the present invention provides a pharmaceutical preparation for treating diabetic nephropathy, the pharmaceutical preparation comprising the effective components of the traditional Chinese medicine composition as described in the first aspect.

[0044] In some embodiments of the present invention, the pharmaceutical preparation further includes pharmaceutically acceptable excipients.

[0045] In some embodiments of the present invention, the excipients include mannitol and microcrystalline cellulose.

[0046] In some embodiments of the present invention, the mass ratio of mannitol to microcrystalline cellulose in the excipients is (1.3-2):1; for example, it can be 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, or 2:1, etc. However, the present invention is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0047] In some embodiments of the present invention, the dosage form of the pharmaceutical preparation is tablets, capsules, granules or oral liquid, preferably granules.

[0048] Thirdly, the present invention provides a method for preparing a pharmaceutical preparation as described in the second aspect, the method comprising the following steps:

[0049] (1) The traditional Chinese medicine composition described in the first aspect is subjected to water extraction to obtain an aqueous extract;

[0050] (2) The aqueous extract is prepared into the dosage form of the drug preparation.

[0051] In some embodiments of the present invention, the water extraction step in step (1) includes: soaking the traditional Chinese medicine composition in water and then decocting it under ultrasonic conditions to obtain the water extract.

[0052] In some embodiments of the present invention, in the step of soaking in water, the mass of the water is 6-12 times the mass of the medicinal material, for example, 6, 7, 8, 9, 10, 11, or 12 times; the soaking time is 1-3 hours, for example, 1 hour, 1.2 hours, 1.5 hours, 1.8 hours, 2 hours, 2.2 hours, 2.5 hours, 2.8 hours, or 3 hours. However, the present invention is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0053] In some embodiments of the present invention, the power of the ultrasound is 100-500W, for example, it can be 100W, 150W, 200W, 250W, 300W, 350W, 400W, 450W, or 500W; the frequency is 20-80kHz, for example, it can be 20kHz, 30kHz, 40kHz, 50kHz, 60kHz, 70kHz, or 80kHz. However, the present invention is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0054] In some embodiments of the present invention, the decoction is performed at least twice (e.g., twice, three times, four times, or five times), and each decoction lasts for 1-3 hours (e.g., 1 hour, 1.2 hours, 1.5 hours, 1.8 hours, 2 hours, 2.2 hours, 2.5 hours, 2.8 hours, or 3 hours). However, the present invention is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0055] In some embodiments of the present invention, in the water extraction step, the total mass of water is 10-30 times the mass of the traditional Chinese medicine composition; for example, it can be 10, 12, 13, 15, 16, 18, 20, 22, 23, 25, 26, 28, or 30 times, etc. However, the present invention is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0056] In some embodiments of the present invention, the dosage form of the pharmaceutical preparation is granules, and step (2) includes:

[0057] The aqueous extract is concentrated to a relative density of 1.05-1.15 at 50°C (e.g., 1.05, 1.06, 1.07, 1.08, 1.09, 1.1, 1.11, 1.12, 1.13, 1.14, or 1.15, etc.) to obtain the first solution;

[0058] A flocculant is added to the first solution to precipitate starch and sugars, and the second solution is obtained by separation.

[0059] The second solution is concentrated into a thick paste with a relative density of 1.30-1.35 at 50°C (e.g., 1.30, 1.31, 1.32, 1.33, 1.34, or 1.35, etc.).

[0060] The thick paste is dried to obtain a dry extract, which is then pulverized and mixed with excipients. The mixture is then granulated using a wet granulation process to form granules. However, this invention is not limited to the listed values; other unlisted values ​​within this range are also applicable.

[0061] In some embodiments of the present invention, the flocculant is chitosan.

[0062] In some embodiments of the present invention, the mass of the flocculant is 0.2-0.6% of the mass of the first solution; for example, it may be 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.55%, or 0.6%, etc. However, the present invention is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0063] In some embodiments of the present invention, the mass ratio of the dry extract to the excipients is (0.8-1.5):(0.9-1.4); for example, it can be 0.8:1.4, 0.8:1.2, 0.8:1, 0.8:0.9, 1:1.4, 1:1.2, 1:1, 1:0.9, 1.2:1.4, 1.2:1, 1.2:0.9, 1.5:1.4, 1.5:1.2, 1.5:1, or 1.5:0.9, etc. However, the present invention is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0064] In some embodiments of the present invention, the excipient is composed of mannitol and microcrystalline cellulose in a mass ratio of (1.3-2):1 (e.g., 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, or 2:1, etc.). However, the present invention is not limited to the listed values, and other unlisted values ​​within this range are equally applicable.

[0065] In some embodiments of the present invention, the concentration method is independently: vacuum concentration at a temperature of 65-70°C (e.g., 65°C, 66°C, 67°C, 68°C, 69°C, or 70°C, etc.) and a vacuum degree of -0.05 to -0.07 MPa (e.g., -0.05 MPa, -0.055 MPa, -0.06 MPa, -0.065 MPa, or -0.07 MPa, etc.). However, the present invention is not limited to the listed values, and other unlisted values ​​within this range are equally applicable.

[0066] In some embodiments of the present invention, the drying method is: vacuum drying at a temperature of 65-70°C (e.g., 65°C, 66°C, 67°C, 68°C, 69°C, or 70°C, etc.) and a vacuum degree of -0.06 to -0.08 MPa (e.g., -0.06 MPa, -0.065 MPa, -0.07 MPa, -0.075 MPa, or -0.08 MPa, etc.). However, the present invention is not limited to the listed values, and other unlisted values ​​within this range are also applicable.

[0067] Compared with the prior art, the present invention has the following beneficial effects:

[0068] This invention utilizes a scientific combination of Astragalus membranaceus, Codonopsis pilosula, Cinnamomum cassia, Cistanche deserticola, Cornus officinalis, Cuscuta chinensis, Atractylodes macrocephala, Atractylodes lancea, Citrus reticulata peel, Poria cocos, Alisma plantago-aquatica, Dioscorea hypoglauca, Corydalis yanhusuo, and Spatholobus suberectus to obtain a traditional Chinese medicine composition and pharmaceutical preparation with good therapeutic effects on diabetic nephropathy. This traditional Chinese medicine composition and pharmaceutical preparation can invigorate the spleen and kidneys, warm and resolve phlegm, and promote blood circulation. It can be used for spleen and kidney qi deficiency, phlegm-dampness stagnation syndrome, with symptoms such as frequent and clear urination, sometimes cloudy urine, fatigue, shortness of breath, poor appetite, abdominal distension, edema, loose stools, chest tightness, epigastric fullness, distending pain or stabbing pain, heaviness of the head and body, fatigue and drowsiness, or skin swelling, numbness, pale purple tongue or spotted tongue, slippery tongue coating, and wiry and hesitant pulse, in diabetic nephropathy with the above symptoms.

[0069] The pharmaceutical preparation provided by this invention has a simple prescription, a simple manufacturing process, few toxic side effects, and is convenient to administer. The preparation is easy to manufacture and has a low cost. Detailed Implementation

[0070] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the specific embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention.

[0071] Example 1

[0072] This embodiment provides a traditional Chinese medicine composition for treating diabetic nephropathy, comprising the following components in parts by weight:

[0073] Astragalus membranaceus 5 parts, Codonopsis pilosula 9 parts, Cinnamomum cassia 4 parts, Cistanche deserticola 9 parts, Cornus officinalis 4 parts, Cuscuta chinensis 12 parts, Atractylodes macrocephala 4 parts, Atractylodes lancea 9 parts, Citrus reticulata 4 parts, Poria cocos 9 parts, Alisma plantago-aquatica 2.5 parts, Dioscorea hypoglauca 9 parts, Corydalis yanhusuo 3 parts, and Spatholobus suberectus 7.5 parts.

[0074] This embodiment also provides a granule formulation for treating diabetic nephropathy, the preparation method of which is as follows:

[0075] (1) Weigh the medicinal materials according to the proportions of the traditional Chinese medicine composition, add 12 times the amount of water as the medicinal materials, and soak for 3 hours to allow the medicinal materials to fully absorb water. Turn on the ultrasonic device (frequency 20kHz, power 100W), heat to boiling under ultrasonic conditions, and then maintain a gentle boil for 1 hour. Filter and collect the first decoction. Add 4 times the amount of water as the medicinal materials to the dregs, and continue to decoct under the above ultrasonic conditions for 3 hours. Filter and collect the second decoction. Combine the two decoctions and perform coarse filtration through a plate and frame filter press to remove larger particulate impurities and improve the clarity of the decoction to obtain an aqueous extract.

[0076] (2) The aqueous extract is transferred to a vacuum concentration tank and concentrated under reduced pressure at a temperature of 70°C and a vacuum degree of -0.05MPa to a relative density of 1.15 at 50°C to obtain the first solution;

[0077] (3) Add 0.6% of chitosan flocculant by mass of the first solution to the first solution, stir evenly and let stand for 2 hours to allow starch and sugars to precipitate, and centrifuge at 8000 r / min for 15 minutes using a tubular centrifuge to further remove fine impurities and obtain a clear second solution.

[0078] (4) The second solution is concentrated into a thick paste with a relative density of 1.35 at 50°C under the conditions of 70°C and a vacuum degree of -0.05MPa.

[0079] (5) The viscous paste is dried under reduced pressure at a temperature of 70°C and a vacuum degree of -0.08MPa to obtain a dry extract (moisture content ≤5%), pulverized, and passed through an 80-mesh sieve to obtain dry extract powder;

[0080] (6) Mix the dry extract powder and excipients at a mass ratio of 0.8:1.4 (the excipients consist of mannitol and microcrystalline cellulose at a mass ratio of 2:1), add an appropriate amount of 80 vol% ethanol aqueous solution as a binder, stir the mixture to form a soft mass, and then use a swing granulator to extrude the soft mass through a 16-mesh sieve to form wet granules; spread the wet granules evenly on a drying tray, place them in a hot air circulating drying oven, and dry them at 65°C until the moisture content is ≤5%. After drying, granules are sieved through an 18-mesh sieve to remove agglomerates and make the granules uniform in size, thus obtaining granules for the treatment of diabetic nephropathy.

[0081] Example 2

[0082] This embodiment provides a traditional Chinese medicine composition for treating diabetic nephropathy, comprising the following components in parts by weight:

[0083] Astragalus membranaceus 15 parts, Codonopsis pilosula 3 parts, Cinnamomum cassia 12 parts, Cistanche deserticola 3 parts, Cornus officinalis 12 parts, Cuscuta chinensis 4 parts, Atractylodes macrocephala 12 parts, Atractylodes lancea 3 parts, Citrus reticulata 12 parts, Poria cocos 3 parts, Alisma plantago-aquatica 7.5 parts, Dioscorea hypoglauca 3 parts, Corydalis yanhusuo 9 parts, and Spatholobus suberectus 2.5 parts.

[0084] This embodiment also provides a granule formulation for treating diabetic nephropathy, the preparation method of which is as follows:

[0085] (1) Weigh the medicinal materials according to the proportions of the traditional Chinese medicine composition, add 6 times the amount of water as the medicinal materials, and soak for 2 hours to allow the medicinal materials to fully absorb water. Turn on the ultrasonic device (frequency 80kHz, power 500W), heat to boiling under ultrasonic conditions, and then maintain a gentle boil for 3 hours. Filter and collect the first decoction. Add 10 times the amount of water as the medicinal materials to the dregs, and continue to decoct under the above ultrasonic conditions for 2 hours. Filter and collect the second decoction. Combine the two decoctions and perform coarse filtration through a plate and frame filter press to remove larger particulate impurities and improve the clarity of the decoction to obtain an aqueous extract.

[0086] (2) The aqueous extract is transferred to a vacuum concentration tank and concentrated under reduced pressure at a temperature of 68°C and a vacuum degree of -0.06MPa to a relative density of 1.05 at 50°C to obtain the first solution;

[0087] (3) Add 0.2% of chitosan flocculant by mass of the first solution to the first solution, stir evenly and let stand for 2 hours to allow starch and sugars to precipitate, and centrifuge at 8000 r / min for 15 minutes using a tubular centrifuge to further remove fine impurities and obtain a clear second solution.

[0088] (4) The second solution was concentrated into a thick paste with a relative density of 1.30 at 50°C under the conditions of 68°C and -0.06MPa.

[0089] (5) The viscous paste is dried under reduced pressure at a temperature of 65°C and a vacuum degree of -0.06MPa to obtain a dry extract (moisture content ≤5%), pulverized, and passed through an 80-mesh sieve to obtain dry extract powder.

[0090] (6) Mix the dry extract powder and excipients at a mass ratio of 1.5:0.9 (the excipients consist of mannitol and microcrystalline cellulose at a mass ratio of 1.3:1), add an appropriate amount of 80 vol% ethanol aqueous solution as a binder, stir the mixture to form a soft mass, and then use a swing granulator to extrude the soft mass through a 16-mesh sieve to form wet granules; spread the wet granules evenly on a drying tray, place them in a hot air circulating drying oven, and dry them at 65°C until the moisture content is ≤5%. After drying, pass the granules through an 18-mesh sieve to remove agglomerates and make the granules uniform in size, thus obtaining granules for the treatment of diabetic nephropathy.

[0091] Example 3

[0092] This embodiment provides a traditional Chinese medicine composition for treating diabetic nephropathy, comprising the following components in parts by weight:

[0093] Astragalus membranaceus 8 parts, Codonopsis pilosula 7.5 parts, Cinnamomum cassia 6 parts, Cistanche deserticola 7.5 parts, Cornus officinalis 6 parts, Cuscuta chinensis 10 parts, Atractylodes macrocephala 6 parts, Atractylodes lancea 7.5 parts, Citrus reticulata 6 parts, Poria cocos 7.5 parts, Alisma plantago-aquatica 4 parts, Dioscorea hypoglauca 7.5 parts, Corydalis yanhusuo 4.5 parts, and Spatholobus suberectus 6 parts.

[0094] This embodiment also provides a granule formulation for treating diabetic nephropathy, the preparation method of which is as follows:

[0095] (1) Weigh the medicinal materials according to the proportions of the traditional Chinese medicine composition, add 8 times the amount of water as the medicinal materials, and soak for 1 hour to allow the medicinal materials to fully absorb water. Turn on the ultrasonic device (frequency 50kHz, power 400W), heat to boiling under ultrasonic conditions, and then maintain a gentle boil for 1.5 hours. Filter and collect the first decoction. Add 6 times the amount of water as the medicinal materials to the dregs, and continue to decoct under the above ultrasonic conditions for 1 hour. Filter and collect the second decoction. Combine the two decoctions and perform coarse filtration through a plate and frame filter press to remove larger particulate impurities and improve the clarity of the decoction to obtain an aqueous extract.

[0096] (2) The aqueous extract is transferred to a vacuum concentration tank and concentrated under reduced pressure at a temperature of 65°C and a vacuum degree of -0.07MPa until the relative density is 1.1 at 50°C, to obtain the first solution;

[0097] (3) Add 0.4% of chitosan flocculant to the first solution, stir evenly, and let stand for 2 hours to allow starch and sugars to precipitate. Centrifuge at 8000 r / min for 15 minutes using a tubular centrifuge to further remove fine impurities and obtain a clear second solution.

[0098] (4) The second solution was concentrated into a thick paste with a relative density of 1.32 at 50°C under the conditions of 65°C and -0.07MPa.

[0099] (5) The viscous paste is dried under reduced pressure at a temperature of 68°C and a vacuum degree of -0.07MPa to obtain a dry extract (moisture content ≤5%), pulverized, and passed through an 80-mesh sieve to obtain dry extract powder;

[0100] (6) Mix the dry extract powder and excipients at a mass ratio of 1.2:1 (the excipients consist of mannitol and microcrystalline cellulose at a mass ratio of 1.8:1), add an appropriate amount of 80 vol% ethanol aqueous solution as a binder, stir the mixture to form a soft mass, and then use a swing granulator to extrude the soft mass through a 16-mesh sieve to form wet granules; spread the wet granules evenly on a drying tray, place them in a hot air circulating drying oven, and dry them at 65°C until the moisture content is ≤5%. After drying, pass the granules through an 18-mesh sieve to remove agglomerates and make the granules uniform in size, thus obtaining granules for the treatment of diabetic nephropathy.

[0101] Example 4

[0102] This embodiment provides a traditional Chinese medicine composition for treating diabetic nephropathy, comprising the following components in parts by weight:

[0103] Astragalus membranaceus 12 parts, Codonopsis pilosula 4.5 parts, Cinnamomum cassia 10 parts, Cistanche deserticola 4.5 parts, Cornus officinalis 10 parts, Cuscuta chinensis 6 parts, Atractylodes macrocephala 10 parts, Atractylodes lancea 4.5 parts, Citrus reticulata 10 parts, Poria cocos 4.5 parts, Alisma plantago-aquatica 6 parts, Dioscorea hypoglauca 4.5 parts, Corydalis yanhusuo 7.5 parts, and Spatholobus suberectus 4 parts.

[0104] This embodiment also provides a granule formulation for treating diabetic nephropathy, the preparation method of which is as follows:

[0105] (1) Weigh the medicinal materials according to the proportions of the traditional Chinese medicine composition, add 8 times the amount of water as the medicinal materials, and soak for 1 hour to allow the medicinal materials to fully absorb water. Turn on the ultrasonic device (frequency 40kHz, power 300W), heat to boiling under ultrasonic conditions, and then maintain a gentle boil for 1.5 hours. Filter and collect the first decoction. Add 6 times the amount of water as the medicinal materials to the dregs, and continue to decoct under the above ultrasonic conditions for 1 hour. Filter and collect the second decoction. Combine the two decoctions and perform coarse filtration through a plate and frame filter press to remove larger particulate impurities and improve the clarity of the decoction to obtain an aqueous extract.

[0106] (2) The aqueous extract is transferred to a vacuum concentration tank and concentrated under reduced pressure at a temperature of 65°C and a vacuum degree of -0.07MPa until the relative density is 1.1 at 50°C, to obtain the first solution;

[0107] (3) Add 0.3% of chitosan flocculant by mass of the first solution to the first solution, stir evenly and let stand for 2 hours to allow starch and sugars to precipitate, and centrifuge at 8000 r / min for 15 minutes using a tubular centrifuge to further remove fine impurities and obtain a clear second solution.

[0108] (4) The second solution was concentrated into a thick paste with a relative density of 1.32 at 50°C under the conditions of 65°C and -0.07MPa.

[0109] (5) The viscous paste is dried under reduced pressure at a temperature of 68°C and a vacuum degree of -0.07MPa to obtain a dry extract (moisture content ≤5%), pulverized, and passed through an 80-mesh sieve to obtain dry extract powder;

[0110] (6) Mix the dry extract powder and excipients at a mass ratio of 1:1 (the excipients consist of mannitol and microcrystalline cellulose at a mass ratio of 1.5:1), add an appropriate amount of 80 vol% ethanol aqueous solution as a binder, stir the mixture to form a soft mass, and then use a swing granulator to extrude the soft mass through a 16-mesh sieve to form wet granules; spread the wet granules evenly on a drying tray, place them in a hot air circulating drying oven, and dry them at 65°C until the moisture content is ≤5%. After drying, granules are sieved through an 18-mesh sieve to remove agglomerates and make the granules uniform in size, thus obtaining granules for the treatment of diabetic nephropathy.

[0111] Example 5

[0112] This embodiment provides a traditional Chinese medicine composition for treating diabetic nephropathy, comprising the following components in parts by weight:

[0113] Astragalus membranaceus 10 parts, Codonopsis pilosula 6 parts, Cinnamomum cassia 8 parts, Cistanche deserticola 6 parts, Cornus officinalis 8 parts, Cuscuta chinensis 8 parts, Atractylodes macrocephala 8 parts, Atractylodes lancea 6 parts, Citrus reticulata 8 parts, Poria cocos 6 parts, Alisma plantago-aquatica 5 parts, Dioscorea hypoglauca 6 parts, Corydalis yanhusuo 6 parts, and Spatholobus suberectus 5 parts.

[0114] This embodiment also provides a granule formulation for treating diabetic nephropathy, the preparation method of which is as follows:

[0115] (1) Weigh the medicinal materials according to the proportions of the traditional Chinese medicine composition, add 8 times the amount of water as the medicinal materials, and soak for 1 hour to allow the medicinal materials to fully absorb water. Turn on the ultrasonic device (frequency 40kHz, power 300W), heat to boiling under ultrasonic conditions, and then maintain a gentle boil for 1.5 hours. Filter and collect the first decoction. Add 6 times the amount of water as the medicinal materials to the dregs, and continue to decoct under the above ultrasonic conditions for 1 hour. Filter and collect the second decoction. Combine the two decoctions and perform coarse filtration through a plate and frame filter press to remove larger particulate impurities and improve the clarity of the decoction to obtain an aqueous extract.

[0116] (2) The aqueous extract is transferred to a vacuum concentration tank and concentrated under reduced pressure at a temperature of 65°C and a vacuum degree of -0.07MPa until the relative density is 1.1 at 50°C, to obtain the first solution;

[0117] (3) Add 0.3% of chitosan flocculant by mass of the first solution to the first solution, stir evenly and let stand for 2 hours to allow starch and sugars to precipitate, and centrifuge at 8000 r / min for 15 minutes using a tubular centrifuge to further remove fine impurities and obtain a clear second solution.

[0118] (4) The second solution was concentrated into a thick paste with a relative density of 1.32 at 50°C under the conditions of 65°C and -0.07MPa.

[0119] (5) The viscous paste is dried under reduced pressure at a temperature of 68°C and a vacuum degree of -0.07MPa to obtain a dry extract (moisture content ≤5%), pulverized, and passed through an 80-mesh sieve to obtain dry extract powder;

[0120] (6) Mix the dry extract powder and excipients at a mass ratio of 1:1 (the excipients consist of mannitol and microcrystalline cellulose at a mass ratio of 1.5:1), add an appropriate amount of 80 vol% ethanol aqueous solution as a binder, stir the mixture to form a soft mass, and then use a swing granulator to extrude the soft mass through a 16-mesh sieve to form wet granules; spread the wet granules evenly on a drying tray, place them in a hot air circulating drying oven, and dry them at 65°C until the moisture content is ≤5%. After drying, granules are sieved through an 18-mesh sieve to remove agglomerates and make the granules uniform in size, thus obtaining granules for the treatment of diabetic nephropathy.

[0121] Comparative Example 1

[0122] The only difference between this comparative example and Example 5 is that ultrasonic treatment is not performed during the decoction process.

[0123] Comparative Example 2

[0124] The only difference between this comparative example and Example 5 is that step (3) is:

[0125] Add ethanol to the first solution until the alcohol content reaches 70 vol%, let stand for 18 hours, and take the supernatant to obtain the second solution.

[0126] Comparative Example 3

[0127] The only difference between this comparative example and Example 5 is that the excipients consist of mannitol and microcrystalline cellulose in a mass ratio of 1:1.

[0128] Process effect test

[0129] 1. Comparison of extraction process routes

[0130] Four portions of the traditional Chinese medicine composition, each weighing 384g (i.e., Astragalus membranaceus 40g, Codonopsis pilosula 24g, Cinnamomum cassia 32g, Cistanche deserticola 24g, Cornus officinalis 32g, Cuscuta chinensis 32g, Atractylodes macrocephala 32g, Atractylodes lancea 24g, Citrus reticulata 32g, Poria cocos 24g, Alisma plantago-aquatica 20g, Dioscorea hypoglauca 24g, Corydalis yanhusuo 24g, and Spatholobus suberectus 20g), were extracted with water using the methods of Example 5 and Comparative Example 1, with two replicates for each method. The extraction efficiency of the two extraction processes was compared using the astragaloside A content in the water extract as an indicator. The test results are shown in Table 1.

[0131] Table 1

[0132]

[0133]

[0134] Note: The astragaloside A content was determined according to the Astragaloside A content determination method under the Astragalus entry on page 323 of the 2025 edition of the Chinese Pharmacopoeia. The astragaloside A content in 40g of Astragalus was 60mg. Aqueous extract 1 and aqueous extract 2 were prepared using the method of Comparative Example 1; aqueous extract 3 and aqueous extract 4 were prepared using the method of Example 5.

[0135] Astragaloside A transfer rate = Total amount of astragaloside A extracted / Total mass of astragaloside A in Astragalus × 100%.

[0136] As can be seen from the data in Table 1, the traditional water decoction method (Comparative Example 1) is relatively mild, but because the cell structure of Astragalus membranaceus is difficult to completely destroy, the dissolution rate of astragaloside A is relatively low, and the content of astragaloside A in the final extract is low.

[0137] The water decoction combined with ultrasound-assisted extraction method (Example 5) can effectively break down Astragalus membranaceus cells and promote the faster and more complete dissolution of astragaloside A. When combined with traditional water decoction, it can significantly increase the content of astragaloside A in the extract and improve the extraction efficiency.

[0138] 2. Comparison of refining process routes

[0139] The aqueous extracts 3 and 4 were mixed thoroughly and divided into two equal portions of 200 mL each. Dry extracts were prepared using the methods described in Example 5 and Comparative Example 2, respectively. The effects of the two purification methods on the astragaloside A content and the properties of the dry extracts were compared. The test results are shown in Table 2.

[0140] Table 2

[0141]

[0142]

[0143] Note: Hygroscopicity was tested according to Method 1 of the Hygroscopicity Test Guidelines, Part IV, 9103 of the 2025 edition of the Chinese Pharmacopoeia. Solubility was tested according to the Solubility Test Method under General Chapter 0104, Granules, Part IV, 2025 edition of the Chinese Pharmacopoeia.

[0144] The experimental results in Table 2 show that the flocculant method (Example 5) has significant advantages over the alcohol precipitation method (Comparative Example 2):

[0145] The flocculant method has a higher retention rate of astragaloside A in the extract and is more suitable for purification scenarios that require the retention of more active ingredients; while the alcohol precipitation method will lead to an increase in the loss of astragaloside A.

[0146] The extract obtained by the flocculant method has a short drying time, is less prone to moisture absorption, and has a loose texture. This method operates at low temperatures throughout, and because the second solution does not contain ethanol, the time required to concentrate to a thick paste is shorter than that of the alcohol precipitation method. This reduces the degradation of components such as astragaloside A caused by high temperatures, which is beneficial for preserving active ingredients and indirectly improves particle quality. Therefore, the flocculant method is more suitable for purification.

[0147] 3. Comparison of pharmaceutical excipients

[0148] Granules were prepared using the methods of Example 5 and Comparative Example 3, respectively, and the effect of the ratio of mannitol to microcrystalline cellulose on the granulation effect was compared. The test results are shown in Table 3.

[0149] Table 3

[0150]

[0151] The experimental results in Table 3 show that when the mass ratio of mannitol to microcrystalline cellulose is 1:1 (the proportion of mannitol is relatively low), due to the strong brittleness of microcrystalline cellulose, the granules are prone to fragmentation, the amount of fine powder increases, it is not easy to form, and the particle size of the granule agent is not full; while when the mass ratio of mannitol to microcrystalline cellulose is 1.5:1, it can not only reduce the generation of fine powder, make the granules easy to form, and the particle size is full, but also ensure that the granules meet the particle size requirements, which not only helps to improve the yield rate, but also improves the taste, and the dissolution of the granules also meets the specified standards.

[0152] Therapeutic effect test

[0153] Take the thick paste prepared in Example 5, dilute it with pure water into a medicinal solution containing 40 vol% of the thick paste amount, and conduct animal experiments to confirm its therapeutic effect on the diabetic nephropathy model induced by injecting streptozotocin solution.

[0154] 1. Experimental animals

[0155] 60 healthy clean-grade SD rats, half male and half female (provided by Beijing Vital River Laboratory Animal Technology Co., Ltd., animal production license number: SCXK(Beijing)2021-0006), at 8 weeks of age, with a body weight of 250±20 g, fed with standard pellet feed and allowed to drink water freely. The ventilation conditions are carried out by an automatic ventilation system, the ventilation frequency is 8-15 times / h, the lighting is 12 h / day, the temperature is 22-26 °C, and the humidity is 50-60%.

[0156] 2. Experimental methods

[0157] 2.1. Grouping and model establishment

[0158] The rats were randomly divided into 6 groups, namely the normal control group, the model control group, the Glibenclamide + Lotensin group, and the high, medium, and low dose groups of the diabetic nephropathy formula. Each group of rats had half male and half female.

[0159] Except for the normal control group, the rats in the other groups were intraperitoneally injected with streptozotocin solution at a dose of 55 mg / kg once to establish a model, and at the same time, a high-sugar and high-fat diet was given. One week later, the rats' tail vein blood was randomly collected to measure fasting blood glucose (BG) and urine volume. A blood glucose ≥ 16.7 mmol / L and a 24-hour urinary protein quantification ≥ 30 mg were used as the criteria for establishing a diabetic nephropathy rat model.

[0160] After successful modeling, rats in each group were administered the drugs by gavage once daily for a total of 8 weeks. The model control group and the blank control group were administered 20 mL / kg·d of physiological saline by gavage; the glucosamine + loperamide group was administered 15 mg / kg·d of glucosamine and 1.5 mg / kg·d of loperamide by gavage; the high, medium, and low dose groups of the diabetic nephropathy formula were all administered a diluted solution of the thick paste prepared in Example 5 by gavage. The dosages (based on the mass of the herbal composition) were: low dose 4.37 g / kg·d, medium dose 8.73 g / kg·d (equivalent to the human equivalent dose), and high dose 17.46 g / kg·d.

[0161] During the experiment, rats were fed a standard diet and had free access to water. Each group was administered the drug continuously for 8 weeks. After the last administration, 24-hour urine samples were collected from each group. Glycated hemoglobin and fasting blood glucose levels were measured by microcolumn chromatography, and 24-hour urinary protein levels were detected using the Coomassie blue method. One hour after the second administration at the end of the 8th week, blood was collected via femoral artery puncture, serum was separated, and serum blood urea nitrogen (BUN), serum creatinine (SCR), serum endogenous creatinine clearance (Ccr), serum triglycerides (TG), and total cholesterol (TC) were measured.

[0162] 4. Experimental Results

[0163] The blood glucose, glycated hemoglobin, and urinary protein content data of each group of rats are shown in Table 1.

[0164] Table 1

[0165]

[0166] Note: Compared with the blank control group, ##p<0.01; compared with the model control group, *p<0.05, **p<0.01.

[0167] As shown in Table 1, compared with the model group, the low-dose diabetic nephropathy formula significantly reduced the levels of blood glucose and glycated hemoglobin in diabetic nephropathy model rats (p<0.05); the medium- and high-dose diabetic nephropathy formulas more significantly reduced the levels of blood glucose and glycated hemoglobin in diabetic nephropathy model rats (p<0.01), and the reduction effect was better than that of the combination of glucosamine and loperamide; the low, medium, and high-dose diabetic nephropathy formulas all significantly reduced the 24-hour urinary protein content in diabetic nephropathy model rats (p<0.01), and the reduction effect was better than that of the combination of glucosamine and loperamide.

[0168] The serum BUN, Scr, and Ccr levels of rats in each group are shown in Table 2.

[0169] Table 2

[0170] Group BUN (mmol / L) Scr (μmol / L) Ccr (ml / min) Blank control group 4.95±0.71 59.31±8.60 1.05±0.12 Model control group 8.62±0.58## 87.17±10.32## 1.55±0.14## Sugar-based + Lodin new combination 8.01±0.62* 77.55±9.53* 1.41±0.13* Low-dose formula for diabetic nephropathy 6.43±0.52** 70.82±8.05** 1.39±0.12* Medium dosage of formula for diabetic nephropathy 5.63±0.70** 65.69±7.48** 1.34±0.14** High-dose formula for diabetic nephropathy 4.78±0.84** 52.01±5.65** 1.34±0.11**

[0171] Note: Compared with the blank control group, ##p<0.01; compared with the model control group, *p<0.05, **p<0.01.

[0172] As shown in Table 2, compared with the model group, low, medium, and high doses of the diabetic nephropathy formula significantly reduced serum BUN and Scr levels in diabetic nephropathy model rats (p<0.01), and the reducing effect was better than that of the combination of glucosamine and loratadine. Medium and high doses of the diabetic nephropathy formula significantly reduced serum Ccr levels in diabetic nephropathy model rats (p<0.01), and the reducing effect was better than that of the combination of glucosamine and loratadine, thus reducing glomerular ultrafiltration overload and protecting kidney function.

[0173] The serum TG and TC levels of rats in each group are shown in Table 3.

[0174] Table 3

[0175] Group TG (mmol / L) TC (mmol / L) Blank control group 1.05±0.12 1.33±0.31 Model control group 3.27±0.67## 3.46±0.86## Sugar-based + Lodin new combination 2.66±0.50* 2.72±0.68* Low-dose formula for diabetic nephropathy 2.48±0.49** 2.51±0.47** Medium dosage of formula for diabetic nephropathy 2.37±0.41** 2.40±0.57** High-dose formula for diabetic nephropathy 2.34±0.48** 2.45±0.63**

[0176] Note: Compared with the blank control group, ##p<0.01; compared with the model control group, *p<0.05, **p<0.01.

[0177] As shown in Table 3, compared with the model group, low, medium and high doses of the diabetic nephropathy formula can significantly reduce the serum TG and TC levels in diabetic nephropathy model rats (p<0.01), and the reducing effect is better than that of the combination of glucosamine and loperamide.

[0178] The above experimental results show that the diabetic nephropathy formula provided by this invention can effectively reduce the relevant physiological indicators of diabetic nephropathy model rats at low, medium and high doses, and has a good therapeutic effect on diabetic nephropathy.

[0179] The above description is merely a specific embodiment of this disclosure, enabling those skilled in the art to understand or implement it. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of this disclosure. Therefore, this disclosure is not to be limited to the embodiments described herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A traditional Chinese medicine composition for treating diabetic nephropathy, characterized in that, The traditional Chinese medicine composition includes the following components: Astragalus, Codonopsis, Cinnamon Twig, Cistanche, Cornus, Cuscuta, Atractylodes Macrocephala, Atractylodes Rhizome, Tangerine Peel, Poria, Alisma Rhizome, Dioscorea Rhizome, Corydalis Rhizome, and Spatholobus Stem.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition comprises the following components in parts by weight: Astragalus membranaceus 5-15 parts, Codonopsis pilosula 3-9 parts, Cinnamomum cassia 4-12 parts, Cistanche deserticola 3-9 parts, Cornus officinalis 4-12 parts, Cuscuta chinensis 4-12 parts, Atractylodes macrocephala 4-12 parts, Atractylodes lancea 3-9 parts, Citrus reticulata 4-12 parts, Poria cocos 3-9 parts, Alisma plantago-aquatica 2.5-7.5 parts, Dioscorea hypoglauca 3-9 parts, Corydalis yanhusuo 3-9 parts, and Spatholobus suberectus 2.5-7.5 parts.

3. The traditional Chinese medicine composition according to claim 1 or 2, characterized in that, The traditional Chinese medicine composition comprises the following components in parts by weight: Astragalus membranaceus 8-12 parts, Codonopsis pilosula 4.5-7.5 parts, Cinnamomum cassia 6-10 parts, Cistanche deserticola 4.5-7.5 parts, Cornus officinalis 6-10 parts, Cuscuta chinensis 6-10 parts, Atractylodes macrocephala 6-10 parts, Atractylodes lancea 4.5-7.5 parts, Citrus reticulata 6-10 parts, Poria cocos 4.5-7.5 parts, Alisma plantago-aquatica 4-6 parts, Dioscorea hypoglauca 4.5-7.5 parts, Corydalis yanhusuo 4.5-7.5 parts, and Spatholobus suberectus 4-6 parts.

4. The traditional Chinese medicine composition according to any one of claims 1-3, characterized in that, The traditional Chinese medicine composition comprises the following components in parts by weight: Astragalus membranaceus 10 parts, Codonopsis pilosula 6 parts, Cinnamomum cassia 8 parts, Cistanche deserticola 6 parts, Cornus officinalis 8 parts, Cuscuta chinensis 8 parts, Atractylodes macrocephala 8 parts, Atractylodes lancea 6 parts, Citrus reticulata 8 parts, Poria cocos 6 parts, Alisma plantago-aquatica 5 parts, Dioscorea hypoglauca 6 parts, Corydalis yanhusuo 6 parts, and Spatholobus suberectus 5 parts.

5. A pharmaceutical preparation for treating diabetic nephropathy, characterized in that, The pharmaceutical preparation contains the active ingredient of the traditional Chinese medicine composition as described in any one of claims 1-4.

6. The pharmaceutical preparation according to claim 5, characterized in that, The pharmaceutical preparation also includes pharmaceutically acceptable excipients; Preferably, the excipients include mannitol and microcrystalline cellulose; Preferably, the mass ratio of mannitol to microcrystalline cellulose in the excipients is (1.3-2):

1.

7. The pharmaceutical preparation according to claim 5 or 6, characterized in that, The dosage form of the pharmaceutical preparation is tablets, capsules, granules, or oral liquid, preferably granules.

8. A method for preparing a pharmaceutical formulation as described in any one of claims 5-7, characterized in that, The preparation method includes the following steps: (1) The traditional Chinese medicine composition according to any one of claims 1-4 is subjected to water extraction to obtain an aqueous extract; (2) The aqueous extract is prepared into the dosage form of the drug preparation.

9. The preparation method according to claim 8, characterized in that, The water extraction step in step (1) includes: soaking the traditional Chinese medicine composition in water, and then decocting it under ultrasonic conditions to obtain the water extract; Preferably, in the step of soaking in water, the mass of the water is 6-12 times the mass of the medicinal material, and the soaking time is 1-3 hours; Preferably, the power of the ultrasound is 100-500W and the frequency is 20-80kHz; Preferably, the decoction is performed at least twice, with each decoction lasting 1-3 hours. Preferably, in the water extraction step, the total mass of water is 10-30 times the mass of the traditional Chinese medicine composition.

10. The preparation method according to claim 8 or 9, characterized in that, The dosage form of the pharmaceutical preparation is granules, and step (2) includes: The aqueous extract was concentrated to a relative density of 1.05-1.15 at 50°C to obtain the first solution; A flocculant is added to the first solution to precipitate starch and sugars, and the second solution is obtained by separation. The second solution was concentrated into a thick paste with a relative density of 1.30-1.35 at 50°C; The thick paste is dried to obtain a dry extract, which is then pulverized and mixed with excipients. The mixture is then granulated by wet granulation to form granules. Preferably, the flocculant is chitosan; Preferably, the mass of the flocculant is 0.2-0.6% of the mass of the first solution; Preferably, the mass ratio of the dry extract to the excipients is (0.8-1.5):(0.9-1.4); Preferably, the excipient is composed of mannitol and microcrystalline cellulose in a mass ratio of (1.3-2):1; Preferably, the concentration method is independently: vacuum concentration at a temperature of 65-70°C and a vacuum degree of -0.05 to -0.07 MPa; Preferably, the drying method is: vacuum drying at a temperature of 65-70℃ and a vacuum degree of -0.06 to -0.08 MPa.

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