A traditional Chinese medicine composition for treating chronic kidney disease and its preparation method and application

Abstract

The present invention discloses a traditional Chinese medicine composition for treating chronic kidney disease, its preparation method, and application, belonging to the technical field of traditional Chinese medicine preparation. The composition is prepared from the following raw materials in parts by weight: 25-40 parts of astragalus, 25-35 parts of raw rehmannia, 25-35 parts of prepared rehmannia, 27-33 parts of ligusticum, 10-20 parts of euryale, 10-20 parts of rosa laevigata fruit, 18-25 parts of cornus fruit with wine, 13-20 parts of schisandra chinensis with vinegar, 10-15 parts of ligustrum lucidum fruit, and 10-15 parts of eclipta. The traditional Chinese medicine composition provided by the present invention has a significant therapeutic effect on patients with chronic kidney disease suffering from kidney deficiency and blood stasis syndrome, characterized by edema, lumbago, fatigue, proteinuria, hematuria, and the like.

Description

Technical Field

[0001] The present invention relates to a traditional Chinese medicine composition for treating chronic kidney disease, a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine preparation. Background Art

[0002] Chronic kidney disease (CKD) is a major chronic condition affecting human health, characterized by high morbidity and mortality, low awareness, high medical costs, and poor prognosis. Current Western medical treatments for CKD primarily focus on controlling the underlying disease, modifying lifestyle, managing risk factors such as hypertension and hyperglycemia, inhibiting overactivation of the renin-angiotensin system, and preventing and treating complications.

[0003] Chronic kidney disease (CKD) falls under the Traditional Chinese Medicine (TCM) categories of "edema," "consumption," and "difficulty," which classify and stage various chronic kidney diseases, including primary and secondary nephropathy, based on the strength of renal function. Traditional Chinese medicine (TCM) offers unique advantages in the treatment of CKD. It can improve the clinical efficacy of patients with CKD, protect renal function, delay renal failure, prevent and treat complications, and offer a high degree of safety. It can also improve patients' clinical symptoms, nutritional status, and quality of life.

[0004] According to Traditional Chinese Medicine (TCM), the primary pathogenesis of early-stage chronic kidney disease is spleen and kidney qi and yin deficiency, with deficiency leading to blood stasis, which in turn generates dampness, and the two dampness and blood stasis interact within the body, acting as a causal force. Currently, early-stage treatments for chronic kidney disease primarily focus on invigorating qi and nourishing yin, tonifying the kidneys and strengthening the spleen. Furthermore, existing TCM preparations for chronic kidney disease lack sufficient attention to the effects of preparation processes or specific active ingredients on therapeutic efficacy. Most TCM preparations are decocted or extracted with water to extract the active ingredients.

[0005] It should be noted that the above content falls within the technical knowledge of the inventor and does not necessarily constitute prior art. Summary of the Invention

[0006] In order to solve the problems existing in the prior art, the present invention provides a Chinese medicine composition for treating chronic kidney disease, a preparation method and application thereof, which has significant therapeutic effect on patients with kidney deficiency and blood stasis syndrome of chronic kidney disease.

[0007] The present invention achieves the above-mentioned purpose by adopting the following technical solutions:

[0008] On the one hand, the present invention provides a traditional Chinese medicine composition for treating chronic kidney disease, which is made from the following raw materials in parts by weight: 25-40 parts of astragalus, 25-35 parts of raw rehmannia, 25-35 parts of cooked rehmannia, 27-33 parts of chuanxiong, 10-20 parts of euryale, 10-20 parts of rose hip, 18-25 parts of cornus officinalis, 13-20 parts of vinegar schisandra, 10-15 parts of wine-soaked ligustrum lucidum, and 10-15 parts of eclipta prostrata.

[0009] Preferably, the traditional Chinese medicine composition for treating chronic kidney disease provided by the present invention is made from the following raw materials in parts by weight: 28-32 parts of astragalus, 28-32 parts of raw rehmannia, 28-32 parts of cooked rehmannia, 27-33 parts of chuanxiong, 12-18 parts of euryale, 12-18 parts of rose hip, 18-22 parts of cornus officinalis, 13-17 parts of vinegar schisandra, 10-12 parts of wine-soaked ligustrum lucidum, and 10-12 parts of eclipta prostrata.

[0010] Furthermore, in one preferred embodiment of the present invention, the weight proportions of each raw material are: 30 parts of Astragalus, 30 parts of Rehmannia root, 30 parts of Rehmannia root, 30 parts of Chuanxiong, 15 parts of Euryale ferox, 15 parts of Rosa laevigata fruit, 20 parts of Cornus officinalis, 15 parts of Schisandra chinensis vinegar, 10 parts of Ligustrum lucidum wine, and 10 parts of Eclipta prostrata.

[0011] Furthermore, in a more preferred embodiment of the present invention, the weight ratio of Astragalus, Raw Rehmannia and Prepared Rehmannia is 1:(0.8-1):(0.8-1).

[0012] On the other hand, the present invention also provides a method for preparing the traditional Chinese medicine composition for treating chronic kidney disease, comprising the following steps:

[0013] (1) Crush Chuanxiong rhizome, wine-infused cornus fruit, and wine-infused Ligustrum lucidum fruit into coarse powder, extract with 80% ethanol by percolation, set aside the residues of Chuanxiong rhizome, wine-infused cornus fruit, and wine-infused Ligustrum lucidum fruit, recover ethanol from the percolation, and concentrate to prepare clear paste A;

[0014] (2) boiling the residues of Chuanxiong, wine-soaked Cornus officinalis, wine-soaked Ligustrum lucidum fruit, and other medicinal materials for preparing the traditional Chinese medicine composition with water, filtering to obtain a filtrate, and concentrating the filtrate under reduced pressure to prepare a clear paste B;

[0015] (3) The clear paste A and the clear paste B are mixed evenly, dried under reduced pressure at 50-60° C., crushed, and dry-granulated to obtain the traditional Chinese medicine composition for treating chronic kidney disease.

[0016] In a preferred embodiment of the present invention, the specific preparation method of the percolate in step (1) is:

[0017] Crush Chuanxiong, wine-soaked Cornus officinalis, and wine-soaked Ligustrum lucidum fruit into 10-20 mesh coarse powder, add 0.5-1 times the weight of 80% ethanol, stir evenly, and fully moisten; put the moistened coarse powder into 2-4 times the weight of 80% ethanol and soak it for 1-2 hours; then add 3.5-5 times the weight of 80% ethanol to immerse the surface of the medicinal materials and fully soak them for 36-48 hours; finally, percolate at a flow rate of 3-5 mL / min per kilogram of coarse powder, and collect the percolation liquid.

[0018] The specific preparation method of the clear paste A in step (1) is: the percolation liquid is concentrated under reduced pressure at 45-55°C to recover ethanol, and the clear paste A having a relative density of 1.08-1.15 at 45°C is prepared.

[0019] In a preferred embodiment of the present invention, the specific preparation method of the filtrate in step (2) is:

[0020] Mix the residues of Chuanxiong, wine-soaked Cornus officinalis, and wine-soaked Ligustrum lucidum evenly with other medicinal materials except Eclipta prostrata, add 10 to 15 times the weight of water, heat to boiling, add Eclipta prostrata, continue to decoct for 1 to 2 hours, filter to obtain the filtrate, add 8 to 12 times the weight of water to the residue, decoct in the same way for 1 to 2 hours, then filter and combine the two filtrates.

[0021] The preparation method of the clear paste B in step (2) is:

[0022] The filtrate was concentrated under reduced pressure at 50-60°C to prepare a clear paste B having a relative density of 1.08-1.15 at 45°C.

[0023] It should be noted that the above preparation method is a preferred preparation method for the Chinese medicine composition of the present invention, and the Chinese medicine composition prepared by the above preparation method has better therapeutic effect.

[0024] In another aspect, the present invention further provides use of the traditional Chinese medicine composition or the traditional Chinese medicine composition prepared by the preparation method in the preparation of a drug for treating chronic kidney disease.

[0025] The advantages of this application include but are not limited to:

[0026] The present invention provides a traditional Chinese medicine composition for treating chronic kidney disease, which uses Rehmannia root, Astragalus root, and Chuanxiong root as the main ingredients, with Rehmannia root being the main ingredient. Among them, Rehmannia root is sweet and warm, nourishes yin and tonifies the kidney, replenishes essence and fills the marrow, and is also good at replenishing blood; Raw Rehmannia root is sweet, cool, and moist, with similar effects to Rehmannia root, but can also counteract its warming properties. The combination of raw and cooked Rehmannia root nourishes yin, replenishes essence, tonifies the kidney, and nourishes blood. Astragalus root can replenish the yang energy of the five internal organs, especially kidney qi. Astragalus root and Rehmannia root are both main ingredients, and have a good effect of strengthening the exterior. Strengthening the exterior strengthens their function of protecting the body from external pathogens, thereby preventing external pathogens. Because any external pathogen can aggravate chronic kidney disease. Chronic kidney disease lasts for a long time, and kidney deficiency and blood stasis occur. Chuanxiong root is the main ingredient for promoting blood circulation and removing blood stasis, promoting the circulation of qi in the blood and blood in the qi. The present invention uses raw and cooked Rehmannia root, Astragalus root, and Chuanxiong root as the main ingredients, which can replenish the kidney and promote blood circulation, thereby eliminating the symptoms of kidney deficiency and blood stasis.

[0027] The present invention uses Rosa laevigata fruit and Euryale ferox fruit as auxiliary drugs, and the two drugs are compatible to tonify the kidney and consolidate the essence. The kidney is responsible for storing essence, and the essence must be consolidated by the kidney. Kidney deficiency causes the essence to be not consolidated, which may lead to kidney essence loss. The "proteinuria" mentioned in modern medicine belongs to this syndrome. Therefore, Rosa laevigata fruit and Euryale ferox fruit, which can not only tonify the kidney but also consolidate the essence, are selected as auxiliary drugs. The two drugs are used together to strengthen the kidney, consolidate the essence, and eliminate various symptoms.

[0028] In addition, the present invention uses wine-soaked cornus fruit, vinegar-soaked schisandra chinensis, wine-soaked ligustrum lucidum fruit, and Eclipta prostrata as adjuvants. Wine-soaked cornus fruit is sour, warm, and moist, warming without being dry, nourishing without being greasy, and can tonify the liver and kidneys, warm the kidneys, and boost yang. It complements rehmannia root and astragalus root, and has a strong ability to dissolve and astringe essence. It is combined with Rosa laevigata fruit and Euryale ferox. Vinegar-soaked schisandra chinensis nourishes the kidneys, replenishes essence, and also strengthens and astringes. Wine-soaked ligustrum lucidum fruit and Eclipta prostrata nourish the liver and kidneys, tonifying yin and blood, and tonifying both the liver and kidneys.

[0029] The present invention first adopts the percolation process to extract fat-soluble functional components, and then adds boiling water and concentrates at low temperature to prevent heat-sensitive components from being destroyed; then adopts the water extraction process to extract water-soluble functional components. The two extraction methods are combined to extract the active ingredients of the medicine to the maximum extent, so that the efficacy is fully exerted.

[0030] Conclusion: The Chinese medicine composition for treating chronic kidney disease provided by the present invention is based on the method of tonifying the kidney and promoting blood circulation, nourishing the yin and yang of the kidney, promoting blood circulation and removing blood stasis, and also consolidating essence and stopping nocturnal emission. Although the combination of monarch, minister, and adjuvant herbs has a theoretical basis in traditional Chinese medicine, pharmacological experiments have shown that replacing similar drugs or ratios cannot achieve the expected efficacy. This composition has a scientific formulation and precise ratios, making it irreplaceable. Clinical data show that the Chinese medicine composition provided by the present invention has a definite overall therapeutic effect, can significantly reduce urine protein and blood creatinine, improve renal function and symptoms, and enhance quality of life, without any toxic side effects. DETAILED DESCRIPTION

[0031] The present invention will be described in further detail below. However, it should be noted that the following specific embodiments are merely illustrative examples of the specific operation of the present invention, and the scope of protection of the present invention is not limited thereto. The scope of protection of the present invention is limited solely by the claims. It will be apparent to those skilled in the art that various other improvements and substitutions can be made to the embodiments of the present invention within the scope of protection defined by the claims of the present invention, and that the same technical effects can still be achieved, thereby achieving the ultimate technical purpose of the present invention.

[0032] Description of the medicinal materials used in this application:

[0033] Astragalus: It is the dried root of Astragalus mongolica or Astragalus membranaceus of the Leguminosae family;

[0034] Raw Rehmannia root: the dried root of Rehmannia root of the Scrophulariaceae plant;

[0035] Cooked Rehmannia root: It is a processed product of raw Rehmannia root. Add water to the raw Rehmannia root, mix thoroughly, steam until it is dark and smooth, take it out, and dry it in the sun until it is about 80% dry. Then cut it into thick slices or blocks and dry it to obtain;

[0036] Chuanxiong: the dried rhizome of the Umbelliferae plant Chuanxiong;

[0037] Gorgon fruit: the dried mature seed kernel of the plant Gorgon of the Nymphaeaceae family;

[0038] Rosa laevigata pulp: the dried outer pulp of the Rosa laevigata fruit of the Rosaceae family. The Rosa laevigata fruit is lightly soaked, moistened thoroughly, cut in two lengthwise, the hair and core removed, and dried.

[0039] Wine-soaked cornus fruit: Made from the dried fruit pulp of Cornus officinalis, a plant of the Cornaceae family, steamed with wine and then dried;

[0040] Vinegar Schisandra: The dried mature fruits of Schisandra chinensis, a plant of the Magnoliaceae family, are steamed with vinegar until black, and crushed before use;

[0041] Ligustrum lucidum fruit: Made from the dried mature fruits of Ligustrum lucidum, a plant of the Oleaceae family, steamed with wine and then dried;

[0042] Eclipta prostrata: the dried above-ground part of the plant Eclipta prostrata of the Asteraceae family.

[0043] Example 1:

[0044] The Chinese medicine composition for treating chronic kidney disease provided in this embodiment is prepared from the following raw materials:

[0045] 300g of Astragalus, 300g of Rehmannia root, 300g of Rehmannia root, 300g of Ligusticum chuanxiong, 150g of Euryale ferox, 150g of Rosa laevigata fruit, 200g of Cornus officinalis with wine, 150g of Schisandra chinensis with vinegar, 100g of Ligustrum lucidum fruit with wine, and 100g of Eclipta prostrata.

[0046] The preparation method of the Chinese medicine composition for treating chronic kidney disease provided in this embodiment is as follows:

[0047] (1) Crush Chuanxiong, wine-soaked Cornus officinalis, and wine-soaked Ligustrum lucidum into 10-20 mesh coarse powder, add 0.5 times the weight of 80% ethanol, stir evenly, and fully wet; put the wetted coarse powder into 80% ethanol twice the weight of the coarse powder and soak it for 1-2 hours; then add 80% ethanol five times the weight of the coarse powder to immerse the medicinal materials on the surface and fully soak them for 48 hours; finally, percolate at a flow rate of 4 mL / min per kg of coarse powder, collect the percolation liquid, and set aside the Chuanxiong, wine-soaked Cornus officinalis, and wine-soaked Ligustrum lucidum residues;

[0048] The percolate is concentrated under reduced pressure at 45-55°C to recover ethanol, and then further concentrated into a clear paste A with a relative density of 1.08-1.15 (measured at 45°C);

[0049] (2) Mix the residues of Chuanxiong, wine-soaked Cornus officinalis, and wine-soaked Ligustrum lucidum with the other medicinal materials except Eclipta prostrata, add 12 times their weight of water, heat to a boil, add Eclipta prostrata, continue to decoct for 2 hours, filter to obtain a filtrate, add 10 times their weight of water to the residue, decoct for 1 hour, filter, and combine the two filtrates;

[0050] The filtrate was concentrated under reduced pressure at 50-60°C to form a clear paste B with a relative density of 1.08-1.15 (measured at 45°C);

[0051] (3) The clear paste A and the clear paste B are mixed evenly, dried under reduced pressure at 50-60° C., crushed to 80-100 mesh, and dry granulated to obtain the traditional Chinese medicine composition for treating chronic kidney disease.

[0052] Example 2:

[0053] The traditional Chinese medicine composition for treating chronic kidney disease provided in this embodiment is prepared from the following raw materials: 250g of Astragalus, 250g of Rehmannia root, 250g of Rehmannia root, 330g of Chuanxiong, 100g of Euryale ferox, 100g of Rosa laevigata fruit, 250g of Cornus officinalis wine-soaked fruit, 200g of Schisandra chinensis vinegar-soaked fruit, 150g of Ligustrum lucidum wine-soaked fruit, and 120g of Eclipta prostrata.

[0054] The preparation method of the Chinese medicine composition for treating chronic kidney disease provided in this embodiment is as follows:

[0055] (1) Crush Chuanxiong, wine-soaked Cornus officinalis, and wine-soaked Ligustrum lucidum into 10-20 mesh coarse powder, add 1 times the weight of 80% ethanol, stir evenly, and fully wet; put the wetted coarse powder into 80% ethanol twice the weight of the coarse powder and soak for 2 hours; then add 80% ethanol five times the weight of the coarse powder to immerse the medicinal materials on the surface and fully soak for 36 hours; finally, percolate at a flow rate of 5 mL / min per kg of coarse powder, collect the percolation liquid, and set aside the Chuanxiong, wine-soaked Cornus officinalis, and wine-soaked Ligustrum lucidum residues;

[0056] The percolate is concentrated under reduced pressure at 45-55°C to recover ethanol, and then further concentrated into a clear paste A with a relative density of 1.08-1.15 (measured at 45°C);

[0057] (2) Mix the residues of Chuanxiong, wine-soaked Cornus officinalis, and wine-soaked Ligustrum lucidum with the other medicinal materials except Eclipta prostrata, add 10 times their weight of water, heat to a boil, add Eclipta prostrata, continue to decoct for 2 hours, filter to obtain a filtrate, add 8 times their weight of water to the residue, decoct for 1 hour, filter, and combine the two filtrates;

[0058] The filtrate was concentrated under reduced pressure at 50-60°C to form a clear paste B with a relative density of 1.08-1.15 (measured at 45°C);

[0059] (3) The clear paste A and the clear paste B are mixed evenly, dried under reduced pressure at 50-60° C., crushed to 80-100 mesh, and dry granulated to obtain the traditional Chinese medicine composition for treating chronic kidney disease.

[0060] Example 3:

[0061] The difference between this embodiment and Example 1 is that it is prepared from the following raw materials: 400g of Astragalus, 350g of Rehmannia root, 350g of Rehmannia root, 270g of Chuanxiong, 200g of Euryale ferox, 200g of Rosa laevigata fruit, 180g of Cornus officinalis with wine, 130g of Schisandra chinensis with vinegar, 200g of Ligustrum lucidum fruit with wine, and 150g of Eclipta prostrata.

[0062] 1. Research on the composition and proportion of Chinese medicine compositions:

[0063] 1.1 Preparation method

[0064] The following samples were prepared according to the preparation method in Example 1 for animal experiments.

[0065] 1.2 Composition of each Chinese medicine composition sample

[0066] Sample of the present invention: YP1

[0067] 300g of Astragalus, 300g of Rehmannia root, 300g of Rehmannia root, 300g of Ligusticum chuanxiong, 150g of Euryale ferox, 150g of Rosa laevigata fruit, 200g of Cornus officinalis with wine, 150g of Schisandra chinensis with vinegar, 100g of Ligustrum lucidum fruit with wine, and 100g of Eclipta prostrata.

[0068] Comparative Example 1: YP2

[0069] 300g of Astragalus, 300g of Rehmannia root, 300g of Rehmannia root, 300g of Chuanxiong, 150g of Euryale ferox, 150g of Rosa laevigata fruit, 200g of Cornus officinalis, 150g of Schisandra chinensis, 100g of Ligustrum lucidum, and 100g of Eclipta prostrata.

[0070] Comparative Example 2: YP3

[0071] Sample 3: 300g of Astragalus, 300g of Rehmannia root, 300g of Rehmannia root, 300g of Salvia miltiorrhiza, 150g of Euryale ferox, 150g of Rosa laevigata fruit, 200g of Cornus officinalis with wine, 150g of Schisandra chinensis with vinegar, 100g of Ligustrum lucidum fruit, and 100g of Eclipta prostrata.

[0072] Comparative Example 3: YP4

[0073] 300g of Astragalus, 300g of Rehmannia root, 300g of Rehmannia root, 300g of Safflower, 150g of Euryale ferox, 150g of Rosa laevigata fruit, 200g of Cornus officinalis with wine, 150g of Schisandra chinensis with vinegar, 100g of Ligustrum lucidum fruit with wine, and 100g of Eclipta prostrata.

[0074] Comparative Example 4: YP5

[0075] 600g of Astragalus, 150g of Raw Rehmannia, 150g of Prepared Rehmannia, 300g of Chuanxiong, 150g of Euryale ferox, 150g of Rosa laevigata fruit, 200g of Cornus officinalis with wine, 150g of Schisandra chinensis with vinegar, 100g of Ligustrum lucidum fruit, and 100g of Eclipta prostrata.

[0076] 1.3 Animal Experimental Methods

[0077] 1.3.1 Experimental animals

[0078] 80 male SD rats, SPF grade, weight 130g±10g, were fed adaptively for 1 week.

[0079] 1.3.2 Grouping and Model Building

[0080] Ten mice were randomly selected as the blank control group and injected with 1 mL of normal saline via the tail vein twice every other week.

[0081] The remaining 70 rats were injected with doxorubicin hydrochloride solution twice every other week through the tail vein, with the first and second injections being 4 mg / kg and 2 mg / kg respectively, for a total of 6 mg / kg.

[0082] Starting from the first day of modeling, the rats were placed in a water tank (35 cm deep, 20-25°C) in batches every day and beaten with a wooden stick to force them to swim continuously until exhaustion (their heads were submerged in the water for 5-10 seconds). After being fished out, they were wiped with a towel and blown dry with an electric hair dryer, and put back into the cage for 14 consecutive days. The breeding temperature was adjusted to 16°C to induce a rat kidney disease model with qi and yin deficiency and blood stasis syndrome.

[0083] Two weeks after the last tail vein injection, all rats were fasted but not watered, and placed in metabolic cages to collect urine for 24 hours. The volume was measured and centrifuged, and the supernatant was taken. The amount of 24-hour urine protein in the rats was measured by an automatic biochemical analyzer. Compared with the blank control group, the 24-hour urine protein was significantly increased (the increase in 24-hour urine protein excretion of rats was 100 mg / 24 hours). －1 ) indicated that the kidney disease model was successfully established.

[0084] The rats with successful modeling were selected and those with symptoms of Qi-Yin deficiency and blood stasis, such as hypoactivity and lethargy, dark purple tongue, subcutaneous ecchymosis of tail, and dry and yellow hair on buttocks, were randomly divided into model group and positive control group (benazepril hydrochloride 1.0×10 －3 g·kg －1 ), the sample group of the present invention, the comparative example group 1, the comparative example group 2, the comparative example group 3, and the comparative example group 4, 8 rats in each group. Gavage was started according to the dosage (the administration volume was 1 ml / 100 g body weight), once a day, for 6 consecutive weeks.

[0085] 1.3.3 Sample Collection

[0086] At the end of the third and sixth weeks of administration, rats in each group were fasted but not watered, placed in metabolic cages to collect urine for 24 hours, measured in volume and centrifuged, and the supernatant was collected and stored in a -80°C refrigerator. After the rats were weighed, they were anesthetized with an intraperitoneal injection of 2% pentobarbital (50 mg / kg), the abdominal cavity was opened along the midline of the abdomen, 5 ml of blood was collected from the abdominal aorta, and the serum was separated by centrifugation and stored in a -80°C refrigerator for the detection of various indicators.

[0087] 1.3.4 Detection indicators

[0088] Urine protein measurement:

[0089] After rat urine samples were appropriately diluted with 0.9% saline, the 24-hour urine protein content of rats was detected by automatic biochemical analyzer (colorimetric method).

[0090] Serum index detection:

[0091] Blood biochemical indicators were detected using a fully automatic blood biochemical analyzer: triglyceride (TG), total cholesterol (TC), creatinine (Scr), serum urea nitrogen (BUN), serum total protein (TP), etc.

[0092] 1.3.5 Experimental results:

[0093] Table 1 Changes in urine protein in rats of each group (n=8, mg / 24h, ))

[0094]

[0095]

[0096] Note: ①Compared with the blank group, * P<0.01; compared with the model group, # P<0.05, ## P < 0.01. ② The dosage was calculated based on the unit body weight, and the equivalent dose for rats was 6.3 times that for humans.

[0097] Compared with the blank group, the model group showed an increase in urine protein levels immediately after successful modeling, and the difference was statistically significant (P < 0.05). Compared with the model group, the 24-hour urine protein levels of all five groups of samples were significantly reduced after 6 weeks of treatment (P < 0.05). Among them, the urine protein levels of the sample group of the present invention decreased most significantly after 3 and 6 weeks of treatment (P < 0.01), indicating the best therapeutic effect.

[0098] Table 2 Changes of serum biochemical indicators in rats in each sample group

[0099] serial number <![CDATA[ALB / (g·L -1 )]]> <![CDATA[BUN / (mmol·L -1 )]]> <![CDATA[Scr / (μmol·L -1 )]]> <![CDATA[TC / (mmol·L -1 )]]> <![CDATA[TG / (mmol·L -1 )]]> <![CDATA[TP / (g·L -1 )]]> KB 37.83±1.42 6.78±1.02 46.44±5.23 2.09±0.56 0.64±0.21 63.39±8.73 MX <![CDATA[26.22±5.45 * ]]> <![CDATA[21.76±3.63 * ]]> <![CDATA[72.0±12.02 * ]]> <![CDATA[3.04±1.11 * ]]> <![CDATA[2.46±0.72 * ]]> <![CDATA[46.65±7.19 * ]]> YX 28.65±3.23 10.74±3.01 69.09±24.16 <![CDATA[2.67±1.04 # ]]> <![CDATA[2.12±0.43 # ]]> 53.13±6.18 YP1 <![CDATA[32.65±4.78 # ]]> <![CDATA[15.04±2.59 ## ]]> <![CDATA[55.77±21.71 ## ]]> <![CDATA[2.38±0.66 # ]]> <![CDATA[2.06±0.39 # ]]> <![CDATA[59.35±8.02 ## ]]> YP2 29.23±4.37 18.04±3.44 <![CDATA[62.39±14.21 # ]]> 2.63±0.81 2.44±0.49 53.63±8.29 YP3 <![CDATA[30.63±5.61 # ]]> <![CDATA[16.90±2.87 # ]]> <![CDATA[63.33±20.33 # ]]> 2.81±1.09 2.28±0.53 <![CDATA[55.30±7.17 # ]]> YP4 29.33±3.12 <![CDATA[17.31±3.23 # ]]> <![CDATA[64.11±28.46 # ]]> 2.76±0.58 2.33±0.62 54.00±8.25 YP5 <![CDATA[30.66±4.82 # ]]> <![CDATA[16.66±3.39 # ]]> <![CDATA[59.49±13.85 # ]]> <![CDATA[2.46±0.53 # ]]> <![CDATA[2.15±0.32 # ]]> <![CDATA[56.89±7.10 # ]]>

[0100] Note: Compared with the blank group, * P<0.05; compared with the model group, # P<0.05, ## P<0.01.

[0101] The above study showed that compared with the model group, the sample group (YP1) of the present invention had significantly decreased serum Scr and Bun levels (P < 0.01), significantly increased TP levels (P < 0.01), and significantly decreased TC and TG levels (P < 0.05) in rats after 6 weeks of treatment. This indicates that the sample of the present invention has a significant scavenging effect on blood creatinine and urea nitrogen in model rats, can increase serum total protein content, and has a certain lipid-lowering effect.

[0102] The above studies show that compared with YP2, the sample of the present invention (YP1) is processed with the same dose of wine-processed Cornus officinalis, vinegar-processed Schisandra chinensis, and wine-processed Ligustrum lucidum fruit, and the extract has a more significant therapeutic effect.

[0103] Compared with samples (YP1), YP3 and YP4 of the present invention, Chuanxiong, Salvia miltiorrhiza and Carthamus tinctorius are all blood-activating and blood-stasis-removing drugs, but the therapeutic effect of Chuanxiong combined with Astragalus membranaceus, Rehmannia glutinosa and other medicinal materials is the best at the same dose. It can not only significantly reduce urine protein and improve the characteristic indicators of kidney disease, but also has a certain lipid-lowering effect. In this prescription, Chuanxiong is irreplaceable for the prescription compatibility.

[0104] The present invention mainly targets the syndrome of qi and yin deficiency and blood stasis. Astragalus nourishes qi and raises yang, while Rehmannia nourishes yin and tonifies the kidney. The dosage of the two needs to be balanced. Comparing the samples of the present invention with YP5, it can be seen that the dosage ratio of Astragalus and Rehmannia in the sample group of the present invention can achieve the best effect.

[0105] The above-mentioned verification experiment of adding and subtracting medicinal ingredients and dosage, and the efficacy verification in a rat kidney model showed that the medicinal materials, dosage and extraction process selected by the present invention have significant therapeutic effects on chronic kidney disease of qi and yin deficiency and blood stasis type.

[0106] 2. Preparation method research:

[0107] Comparative Example 5:

[0108] In this comparative example, the weight proportions of the medicinal materials in the Chinese medicine composition are the same as those in Example 1. The Chinese medicine composition is extracted by ethanol reflux, and the specific method is as follows:

[0109] (1) Crush Chuanxiong, wine-soaked Cornus officinalis, and wine-soaked Ligustrum lucidum into coarse powder, add 10 times the weight of 80% ethanol, heat to boiling, continue to reflux for 2 hours, and concentrate under reduced pressure at 50-60°C to obtain a clear paste A with a relative density of 1.08-1.15 (measured at 45°C);

[0110] (2) Mix the residues of Chuanxiong, wine-brewed Cornus officinalis, and wine-brewed Ligustrum lucidum with other medicinal materials, add 12 times the weight of water, heat to boiling, and continue to decoct for 2 hours. Filter to obtain the filtrate. Add 10 times the weight of water to the residue and decoct for 1 hour in the same manner. Filter and combine the two filtrates.

[0111] The filtrate was concentrated under reduced pressure at 50-60°C to form a clear paste B with a relative density of 1.08-1.15 (measured at 45°C);

[0112] (3) Mix the paste A and the paste B evenly, dry under reduced pressure at 50-60°C, grind to 80-100 mesh, and dry granulate.

[0113] Comparative Example 6:

[0114] In this comparative example, the weight proportions of the medicinal materials in the Chinese medicine composition are the same as those in Example 1. The Chinese medicine composition is extracted by water decoction. The specific method is as follows:

[0115] Mix all the medicinal materials evenly, add 12 times the weight of water, heat to boiling and continue to decoct for 2 hours, filter, add 10 times the amount of water to the residue and continue to decoct for 1 hour, filter, combine the filtrate, and concentrate under reduced pressure at 50-60°C to form a clear paste with a relative density of 1.08-1.15 (measured at 45°C), dry under reduced pressure at 50-60°C, crush to 80-100 mesh, and granulate by dry method.

[0116] Table 3 shows the distribution and content of the main active ingredients in Example 1, Comparative Example 5 and Comparative Example 6 under different extraction methods.

[0117] Table 3 Distribution and content of main active ingredients under different extraction methods (mg)

[0118]

[0119] Note: “-” means below the detection limit or not detected.

[0120]

[0121] Where i is the number of the active ingredient, P i is the weight of each active ingredient, X i The content of each active ingredient in the same extract, This is the highest content of the same active ingredient obtained by different extraction methods.

[0122] The above studies show that the extraction efficiency of each active ingredient in the Chinese medicine composition is different when using different extraction methods. According to the comprehensive evaluation of the weight of each ingredient, the G value of the preparation method in Example 1 is the highest, and the active ingredients are extracted more fully.

[0123] The preparation method provided by the present invention is further investigated by orthogonal test process as follows.

[0124] Table 4 Orthogonal test results of factors affecting percolation extraction in the preparation method of the present invention

[0125]

[0126] The material-liquid ratio refers to the weight ratio of coarse powder to ethanol.

[0127] From the orthogonal test results in Table 4, it can be seen that the G value of the comprehensive score of the weight of each component is used as an indicator. The largest range is 0.08. Combining the range and variance analysis, it can be obtained that the influence of each factor is B>C>A. The ethanol concentration has the most obvious effect on the extraction results. The optimal process is A2B2C3, that is, the material-liquid ratio is 1:8, the ethanol concentration is 80%, and the infiltration time is 48h.

[0128] The preparation method in Example 1 of the present invention first uses a percolation process to extract fat-soluble effective components and then concentrates them at low temperature to protect heat-sensitive components from being destroyed; then a water extraction process is used to extract water-soluble effective components. The combination of these two extraction methods maximizes the extraction of active ingredients of the drug, so that the efficacy is fully exerted.

[0129] 3. Clinical trials

[0130] The samples of the present invention were used to conduct a clinical efficacy study on patients with chronic kidney disease.

[0131] This study enrolled 63 patients with chronic kidney disease who met the inclusion criteria. The average duration of disease was 5.3 years. These patients had long-standing symptoms, including varying degrees of edema, foamy urine, hematuria, low back pain, and fatigue. They had been treated with similar prescriptions at regular hospitals for over a year with limited success.

[0132] 3.1 Clinical samples: After preparing the drug powder according to the preparation method of Example 1 and the optimal extraction process parameters obtained by orthogonal test, 0.5 to 1 times the weight of dextrin was added, dry granulated, and bagged at 6 g / bag.

[0133] 3.2 Diagnostic criteria

[0134] 3.2.1 TCM Syndrome Differentiation Standards (Kidney Deficiency and Blood Stasis Syndrome)

[0135] (1)Zheng deficiency syndrome

[0136] Qi and Yin deficiency syndrome:

[0137] Main symptoms: fatigue, soreness of waist and knees, dry mouth and throat, hot flashes in the five parts of the body, chills and cold limbs, low back pain or edema.

[0138] Secondary symptoms: clear and long urine at night, pale tongue with teeth marks, and deep pulse.

[0139] (2) Evidence

[0140] Blood stasis syndrome:

[0141] Main symptoms: Dull complexion, fixed or stabbing lower back pain.

[0142] Secondary symptoms: skin and nails are cracked, limbs are numb, tongue is dark purple or has petechiae and ecchymosis, pulse is sluggish or thready.

[0143] 3.2.2 Western medicine diagnostic standards

[0144] Refer to the Guidelines for Early Screening, Diagnosis and Prevention of Chronic Kidney Disease (2022 Edition) (Chinese Journal of Nephrology, Vol. 38, No. 5, 2022) for the diagnostic criteria for chronic kidney disease (CKD): CKD can be diagnosed if any of the indicators in the table below appears and lasts for more than 3 months.

[0145] Table 5 Diagnostic criteria for chronic kidney disease (CKD)

[0146]

[0147]

[0148] 3.3 Criteria for inclusion, exclusion, elimination, and termination of trials

[0149] 3.3.1 Inclusion and Exclusion Criteria

[0150] Table 6 Inclusion and exclusion criteria for clinical cases

[0151]

[0152]

[0153] 3.3.2 Rejection and shedding criteria

[0154] (1) Cases that met the inclusion criteria but did not take medication after inclusion were excluded.

[0155] (2) Patients with poor compliance who do not take medication as prescribed, who experience serious adverse events, or who have special physiological changes and are not suitable to continue the trial are considered dropouts.

[0156] 3.3.3 Test termination criteria:

[0157] (1) Those whose symptoms or signs worsen after taking the medication and refuse to continue taking the medication

[0158] (2) Subjects with poor medication compliance and unsuitable to continue the trial

[0159] (3) Those who have adverse reactions and are not suitable to continue the trial.

[0160] If any of the above criteria is met, the trial can be terminated.

[0161] 3.4 Treatment methods

[0162] The 63 patients with chronic kidney disease were treated with the same sample of the present invention, taken with boiled water, 3 times a day, 1 bag each time, 6 g / bag, for 12 consecutive weeks.

[0163] 3.5 Evaluation indicators

[0164] 3.5.1 Main symptoms and signs

[0165] Based on the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines (Trial Implementation)" (2002), a symptom grading table was developed. For symptoms classified into three levels: mild, moderate, and severe, primary symptoms are scored as 2 points for mild, 4 points for moderate, and 6 points for severe. Secondary symptoms are scored as 1 point for mild, 2 points for moderate, and 3 points for severe. Based on this standard, syndrome scores are assigned.

[0166] Table 7 TCM symptom grading and quantification table

[0167]

[0168]

[0169] Note: Specific description of tongue and pulse will not be scored.

[0170] 3.5.2 Biochemical test indicators

[0171] Changes in UACR, BUN, serum Scr, and CysC compared with baseline.

[0172] 3.5.3 Safety evaluation Safety indicators: liver function, kidney function, electrocardiogram, blood routine, urine routine, stool routine.

[0173] 3.6 Efficacy Assessment

[0174] 3.6.1 Criteria for determining efficacy

[0175] (1) Significant effect

[0176] ① The clinical symptom score is reduced by ≥70%.

[0177] ②eGFR increased by ≥20%.

[0178] ③ Blood creatinine decreased by ≥20%.

[0179] Item ① above is essential, and if one of ② and ③ is met, the judgment can be made.

[0180] (2) Effective

[0181] ① The clinical symptom score is reduced by ≥30%.

[0182] ②eGFR increased by ≥10%.

[0183] ③ Blood creatinine decreased by ≥10%.

[0184] ④ The logarithm or reciprocal of serum creatinine before and after treatment was analyzed using a linear regression equation, and the slope was significant.

[0185] Item ① above is essential, and the other item can be judged if it is met.

[0186] (3) Stability

[0187] ① Clinical symptoms improved, with the score reduced by <30%.

[0188] ②eGFR does not decrease, or increases by <10%.

[0189] ③ There is no increase in blood creatinine, or a decrease of <10%.

[0190] Item ① above is essential, and if one of ② and ③ is met, the judgment can be made.

[0191] (4) Invalid

[0192] ①Clinical symptoms do not improve or worsen.

[0193] ② Decreased eGFR.

[0194] ③ Increased blood creatinine.

[0195] Item ① above is essential, and if one of ② and ③ is met, the judgment can be made.

[0196] 3.6.2 Safety evaluation standards

[0197] Level ①: safe, without any adverse reactions;

[0198] Level ②: relatively safe. If there are adverse reactions, no treatment is required and the drug can be continued.

[0199] Level ③: There are safety issues and moderate adverse reactions, and the drug can continue to be administered after treatment;

[0200] Grade ④: The trial was terminated due to adverse reactions.

[0201] 3.7 Results

[0202] During the treatment with the composition of the present invention, 4 patients dropped out, with a dropout rate of 6%.

[0203] 3.7.1 Efficacy results

[0204] Table 8 Clinical efficacy results

[0205] Number of cases Significantly effective efficient Stablize invalid Total effective rate (%) 59 36 14 6 3 94.9％

[0206]

[0207] The results listed in the table above show that the total effective rate of the comprehensive treatment of chronic kidney disease by the present invention is 94.9%, and it has a very good effect in improving clinical symptoms and clearing creatinine. This shows that the present invention has a significant therapeutic effect on chronic kidney disease with Qi and Yin deficiency and blood stasis syndrome.

[0208] 3.7.2 Comparison of main biochemical indicators before and after treatment

[0209] The changes in UACR levels, renal function (BUN, SCr), and serum Cysc levels before and after treatment are shown in the table below.

[0210] Table 9 Main observation index level detection (n=59, )

[0211] index UACR (mg / g) <![CDATA[Scr / (μmol·L -1 )]]> <![CDATA[BUN(mmol·L -1 )]]> <![CDATA[Cysc(mg·L -1 )]]> Before treatment 227.2±29.3 301.45±44.17 13.34±4.12 1.54±0.31 After treatment <![CDATA[107.6±37.2 ▲ ]]> <![CDATA[210.33±36.68 ▲ ]]> 8.77±3.34* 1.19±0.17*

[0212] Note: Compared with before treatment, ▲ P<0.01; *P<0.05.

[0213] The results listed in the table above show that before and after treatment, the levels of BUN and Cysc decreased, which were statistically significant compared with those before treatment (P<0.05). Among them, Scr and UACR decreased significantly (P<0.01), indicating that the composition of the present invention has the effect of significantly reducing blood creatinine and urine protein.

[0214] Table 10 Comparison of safety factors during patient treatment

[0215] n Level 1 Level 2 Level 3 Level 4 59 52 7 0 0

[0216] As can be seen from the above table, all patients did not experience grade 3 or 4 adverse reactions. During the treatment, there were no abnormal changes in the patients' blood routine, urine routine, liver function, electrocardiogram, etc.

[0217] From the above results, it can be seen that the sample of the present invention has a good effect on improving the clinical symptoms of patients with chronic kidney disease with qi and yin deficiency and blood stasis syndrome, and can nourish the kidney and promote blood circulation, consolidate essence and stop nocturnal emission; at the same time, it can significantly improve the patient's renal function indicators such as blood creatinine and urine protein, and can be taken for a long time, with high safety, small side effects and stable therapeutic effects.

[0218] The above specific implementation manner cannot be used as a limitation on the protection scope of the present invention. For those skilled in the art, any replacement, improvement or transformation made to the implementation manner of the present invention falls within the protection scope of the present invention.

[0219] Any matters not described in detail in the present invention are well-known technologies to those skilled in the art.

Claims

1. A Chinese medicine composition for treating chronic kidney disease, characterized in that: The invention is prepared from the following raw materials in parts by weight: 25-40 parts of astragalus, 25-35 parts of raw rehmannia, 25-35 parts of cooked rehmannia, 27-33 parts of ligusticum, 10-20 parts of euryale, 10-20 parts of rosa laevigata fruit pulp, 18-25 parts of cornus fruit with wine, 13-20 parts of schisandra chinensis with vinegar, 10-15 parts of ligustrum lucidum fruit with wine, and 10-15 parts of eclipta prostrata. The method for preparing the traditional Chinese medicine composition for treating chronic kidney disease comprises the following steps: (1) Crush Chuanxiong rhizome, wine-infused cornus fruit, and wine-infused Ligustrum lucidum fruit into coarse powder, extract with 80% ethanol by percolation, set aside the residues of Chuanxiong rhizome, wine-infused cornus fruit, and wine-infused Ligustrum lucidum fruit, recover ethanol from the percolation, and concentrate to prepare clear paste A; (2) boiling the residues of Chuanxiong, wine-soaked Cornus officinalis, wine-soaked Ligustrum lucidum fruit, and other medicinal materials for preparing the traditional Chinese medicine composition with water, filtering to obtain a filtrate, and concentrating the filtrate under reduced pressure to prepare a clear paste B; (3) The clear paste A and the clear paste B are mixed evenly, dried under reduced pressure at 50-60° C., crushed, and dry-granulated to obtain the traditional Chinese medicine composition for treating chronic kidney disease.

2. The Chinese medicine composition for treating chronic kidney disease according to claim 1, characterized in that The weight proportions of the raw materials are as follows: 30 parts of Astragalus, 30 parts of Rehmannia root, 30 parts of Rehmannia root, 30 parts of Chuanxiong, 15 parts of Euryale ferox, 15 parts of Rosa laevigata fruit, 20 parts of Cornus officinalis, 15 parts of Schisandra chinensis vinegar, 10 parts of Ligustrum lucidum wine, and 10 parts of Eclipta prostrata.

3. The Chinese medicine composition for treating chronic kidney disease according to claim 1, characterized in that The weight ratio of astragalus, raw rehmannia and cooked rehmannia is 1:(0.8-1):(0.8-1).

4. The Chinese medicine composition for treating chronic kidney disease according to claim 1, characterized in that The specific preparation method of the percolate in step (1) is: Crush Chuanxiong, wine-soaked Cornus officinalis, and wine-soaked Ligustrum lucidum fruit into 10-20 mesh coarse powder, add 0.5-1 times the weight of 80% ethanol, stir evenly, and fully moisten; put the moistened coarse powder into 2-4 times the weight of 80% ethanol and soak it for 1-2 hours; then add 3.5-5 times the weight of 80% ethanol to immerse the surface of the medicinal materials and fully soak them for 36-48 hours; finally, percolate at a flow rate of 3-5 mL / min per kilogram of coarse powder, and collect the percolation liquid.

5. The Chinese medicine composition for treating chronic kidney disease according to claim 1, characterized in that: The specific preparation method of the clear paste A in step (1) is: the percolation liquid is concentrated under reduced pressure at 45-55°C to recover ethanol, and the clear paste A having a relative density of 1.08-1.15 at 45°C is prepared.

6. The Chinese medicine composition for treating chronic kidney disease according to claim 1, characterized in that: The specific preparation method of the filtrate in step (2) is: Mix the residues of Chuanxiong, wine-soaked Cornus officinalis, and wine-soaked Ligustrum lucidum evenly with other medicinal materials except Eclipta prostrata, add 10 to 15 times the weight of water, heat to boiling, add Eclipta prostrata, continue to decoct for 1 to 2 hours, filter to obtain the filtrate, add 8 to 12 times the weight of water to the residue, decoct in the same way for 1 to 2 hours, then filter and combine the two filtrates.

7. The Chinese medicine composition for treating chronic kidney disease according to claim 1, characterized in that: The preparation method of the clear paste B in step (2) is: The filtrate was concentrated under reduced pressure at 50-60°C to prepare a clear paste B having a relative density of 1.08-1.15 at 45°C.

8. A use of the traditional Chinese medicine composition according to any one of claims 1 to 7, characterized in that: The traditional Chinese medicine composition is used for preparing medicine for treating chronic kidney disease.

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