A traditional Chinese medicine preparation for preventing or treating chronic kidney disease, a preparation method and application thereof

Abstract

The application provides a traditional Chinese medicine preparation for preventing or treating chronic kidney disease and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine preparations. The traditional Chinese medicine preparation is prepared from wine female ligustrum fruit, eclipta, astragalus root, codonopsis root, rehmannia root, imperata cylindrical root, madder, biota leaf, hawksbeard, red peony root, lotus node and licorice. The different traditional Chinese medicines are extracted for active sites, and meanwhile, pregelatinized starch, microcrystalline cellulose, calcium hydrogen phosphate and microfine silica gel are used to prepare capsule or granules. The traditional Chinese medicine preparation has remarkable curative effect and good safety, and the stability and disintegration time limit of the preparation are significantly improved, and the compliance of patients is increased.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparation technology, specifically relating to a traditional Chinese medicine preparation for the prevention or treatment of chronic kidney disease, its preparation method, and its application. Background Technology

[0002] Chronic kidney disease (CHD) refers to a group of diseases characterized by abnormalities in kidney structure or function lasting more than three months and impacting health. It is typically caused by various factors, such as diabetes and hypertension. Long-term high blood sugar and high blood pressure, especially when not actively controlled, can lead to hypertensive nephropathy and diabetic nephropathy. These diseases often have no obvious symptoms in their early stages, but as the disease progresses, symptoms such as edema, increased foamy urine, and increased frequency of urination at night may appear.

[0003] Chronic kidney disease (CKD) is a global public health problem. With improved living standards and changing dietary habits, the number of people suffering from hypertension and diabetes is increasing year by year, and the prevalence of CKD is also continuously rising. It is reported that in 2021, 850 million people worldwide suffered from kidney disease due to various causes, resulting in at least 2.4 million deaths annually. In my country, the number of adult CKD patients is as high as 120 million, with 1 to 2 million patients in end-stage renal disease, and an annual growth rate exceeding 15%.

[0004] The core of TCM treatment for chronic kidney disease is to strengthen the body's resistance and eliminate pathogenic factors, addressing both the root cause and the symptoms. Chronic kidney disease has a long course and is prone to deficiency syndromes such as spleen and kidney qi deficiency, liver and kidney yin deficiency, and qi and yin deficiency. Strengthening the body's resistance can slow the progression of kidney damage. At the same time, for symptoms such as dampness, blood stasis, and damp-heat that appear during the course of the disease, methods such as promoting diuresis and eliminating turbidity, activating blood circulation and removing blood stasis, and clearing heat and eliminating dampness can be used to reduce the pathological burden on the kidneys.

[0005] Because chronic kidney disease (CKD) often presents with no symptoms in its early stages, many patients only seek medical attention when the condition has progressed to a severe stage. Therefore, prevention and early intervention are crucial. Traditional Chinese medicine (TCM) emphasizes holistic treatment, addressing multiple systemic issues. It reduces the side effects of Western medicine while improving drug tolerance, thus offering advantages in the treatment of CKD. Given this, there remains a need to develop TCM formulas for the prevention or treatment of CKD. Summary of the Invention

[0006] In view of current needs, the purpose of this invention is to provide a traditional Chinese medicine preparation for the prevention or treatment of chronic kidney disease, its preparation method, and its application. The traditional Chinese medicine preparation of this invention has significant efficacy, is safe to take, and no adverse reactions have been found in humans so far. Through research on traditional Chinese medicine extraction and preparation processes, compared with traditional decoctions, it not only improves efficacy but also significantly enhances drug stability and disintegration time, increasing patient compliance and providing a safe and effective traditional Chinese medicine preparation for patients with chronic kidney disease.

[0007] In a first aspect of the present invention, a traditional Chinese medicine preparation for the prevention or treatment of chronic kidney disease is provided.

[0008] In one specific embodiment, the present invention provides a traditional Chinese medicine preparation for the prevention or treatment of chronic kidney disease, the active ingredients of which are made from the following traditional Chinese medicine raw materials in parts by weight: 50-120 parts of Ligustrum lucidum, 50-120 parts of Eclipta prostrata, 180-250 parts of Astragalus membranaceus, 100-180 parts of Codonopsis pilosula, 60-150 parts of Rehmannia glutinosa, 100-180 parts of Imperata cylindrica, 40-110 parts of Rubia cordifolia, 50-120 parts of Platycladus orientalis, 60-150 parts of Sanguisorba officinalis, 50-120 parts of Paeonia lactiflora, 60-150 parts of Nelumbo nucifera rhizome, and 40-110 parts of Glycyrrhiza uralensis.

[0009] Preferably, the active ingredients of the traditional Chinese medicine preparation are made from the following traditional Chinese medicine raw materials in parts by weight: 68-100 parts of Ligustrum lucidum, 68-100 parts of Eclipta prostrata, 195-225 parts of Astragalus membranaceus, 120-160 parts of Codonopsis pilosula, 80-120 parts of Rehmannia glutinosa, 120-160 parts of Imperata cylindrica, 55-95 parts of Rubia cordifolia, 68-100 parts of Platycladus orientalis, 80-120 parts of Sanguisorba officinalis, 68-100 parts of Paeonia lactiflora, 80-120 parts of Nelumbo nucifera rhizome, and 55-95 parts of Glycyrrhiza uralensis.

[0010] More preferably, the active ingredients of the traditional Chinese medicine preparation are made from the following traditional Chinese medicine raw materials in parts by weight: 85.7 parts of Ligustrum lucidum, 85.7 parts of Eclipta prostrata, 214.3 parts of Astragalus membranaceus, 142.9 parts of Codonopsis pilosula, 107.1 parts of Rehmannia glutinosa, 142.9 parts of Imperata cylindrica, 71.4 parts of Rubia cordifolia, 85.7 parts of Platycladus orientalis, 107.1 parts of Sanguisorba officinalis, 85.7 parts of Paeonia lactiflora, 107.1 parts of Nelumbo nucifera rhizome, and 71.4 parts of Glycyrrhiza uralensis.

[0011] The sources and efficacy of the traditional Chinese medicine raw materials used in the prescription of this invention are as follows:

[0012] Wine-processed privet fruit: The dried, ripe fruit of *Ligustrum lucidum* Ait., a plant in the Oleaceae family. Harvested in winter when the fruit is ripe, the branches and leaves are removed, and the fruit is lightly steamed and then dried; or dried directly. It is a processed product of privet fruit. It is commonly used for dizziness, blurred vision, and weakness in the lower back and knees caused by liver and kidney yin deficiency.

[0013] Eclipta prostrata L. (also known as black eclipta): The dried aerial parts of the plant, belonging to the Asteraceae family. Harvested when in bloom and dried in the sun. It has the effects of nourishing the liver and kidneys, cooling the blood, and stopping bleeding; it is suitable for bleeding symptoms caused by yin deficiency and blood heat.

[0014] Astragalus: The dried root of *Astragalus membranaceus* (Fisch.) Bge. var. *mongholicus* (Bge.) Hsiao, a plant in the legume family. It is harvested in spring and autumn, with the fibrous roots and root head removed, and then dried in the sun. It has the effects of tonifying qi and raising yang, consolidating the exterior and stopping sweating.

[0015] Codonopsis pilosula (Franch.) Nannf., a plant in the Campanulaceae family, is the dried root of the plant. It is harvested in autumn, washed, and sun-dried. It has the functions of tonifying the middle energizer, replenishing qi, strengthening the spleen, and benefiting the lungs.

[0016] Rehmannia glutinosa: The dried tuberous root of Rehmannia glutinosa Libosch., a plant in the Scrophulariaceae family. Harvested in autumn, the rhizome, fibrous roots, and soil are removed, and the root is slowly baked until about 80% dry. It has the effects of clearing heat and cooling blood, nourishing yin and promoting body fluid production.

[0017] Imperata cylindrica root: The dried rhizome of Imperata cylindrica Beauv. var. major (Nees) CE Hubb., a plant of the Poaceae family. It is harvested in spring and autumn, washed, dried, and the fibrous roots and membranous leaf sheaths are removed before being bundled into small bunches. It has the effects of cooling the blood and stopping bleeding, clearing heat and promoting diuresis.

[0018] Madder root: The dried root and rhizome of Rubia cordifolia L., a plant in the Rubiaceae family. Harvested in spring and autumn, the roots and rhizomes are removed from the soil and dried. It has the effects of cooling the blood and stopping bleeding, promoting blood circulation and removing blood stasis. While stopping bleeding, it also promotes blood circulation, avoiding the blood stasis caused by hemostatic drugs.

[0019] Chinese arborvitae leaves: These are the dried branches and leaves of *Platycladus orientalis* (L.) Franco, a plant in the Cupressaceae family. They are mostly harvested in summer and autumn and dried in the shade. They have the effects of cooling the blood and stopping bleeding, resolving phlegm and relieving cough, and can be used for various types of bleeding due to blood heat, such as hemoptysis, hematemesis, and hematochezia. They can also clear lung heat. Chinese arborvitae leaves are rich in volatile oils, which can inhibit various pathogenic bacteria and promote blood clotting, while also possessing certain antioxidant and sedative effects.

[0020] Sanguisorba officinalis L., a plant in the Rosaceae family, is the dried root of the plant. It is harvested in autumn after the plant has withered, the fibrous roots are removed, and it is washed and dried. It has the effects of cooling the blood and stopping bleeding, detoxifying and astringing sores, and can treat hematochezia, hemorrhoidal bleeding, and metrorrhagia caused by heat in the lower abdomen. The volatile oil of Sanguisorba officinalis is one of its active ingredients and plays an auxiliary role in anti-inflammatory and antibacterial properties.

[0021] Red peony root: the dried root of Paeonia lactiflora Pall., a plant in the Ranunculaceae family. It is harvested in spring and autumn, with the rhizomes, fibrous roots, and soil removed before being sun-dried. It has the effects of clearing heat and cooling the blood, dispersing blood stasis and relieving pain. It not only assists in cooling the blood and stopping bleeding, but also improves blood circulation by dispersing blood stasis.

[0022] Lotus root nodes: These are the dried rhizome nodes of Nelumbo nucifera Gaertn., a plant in the Nymphaeaceae family. The rhizomes (lotus roots) are harvested in autumn and winter, the nodes are cut off, washed, dried, and the fibrous roots are removed. They have astringent, hemostatic, and blood-stasis-removing effects; their medicinal properties are mild, stopping bleeding without causing blood stasis.

[0023] Licorice: The dried root and rhizome of *Glycyrrhiza uralensis* Fisch., a plant in the legume family. It is harvested in spring and autumn, the fibrous roots are removed, and it is then sun-dried. It has the effects of tonifying the spleen and replenishing qi, and harmonizing other medicinal ingredients.

[0024] The formula of this invention is scientifically formulated. The *Ligustrum lucidum* (fragrant privet fruit) is sweet and enters the liver and kidney meridians, nourishing the liver and kidneys, and strengthening the brain and replenishing essence. It nourishes the liver and kidneys without being cloying, and replenishes essence and blood without causing stagnation. *Eclipta prostrata* (sweet and sour lotus) also enters the liver and kidney meridians, nourishing the liver and kidneys, replenishing essence, and cooling the blood to stop bleeding. The two herbs work synergistically, benefiting both the lower and upper parts of the body, and together they nourish the liver and kidneys, cool the blood, and stop bleeding, serving as the principal herbs. *Astragalus membranaceus* (Astragalus membranaceus) invigorates qi and strengthens the exterior, tonifies the spleen and raises yang; *Codonopsis pilosula* (Codonopsis pilosula) invigorates qi and nourishes yin. Together, they strengthen the spleen and invigorate qi, nourishing both acquired and innate constitutions. *Rehmannia glutinosa* (Rehmannia glutinosa) is sweet, bitter, and cold, nourishing kidney yin, cooling the blood, and stopping bleeding. These three herbs enhance the liver and kidney tonifying effect of the principal herbs, serving as the assistant herbs. *Imperata cylindrica* (Imperata cylindrica root), *Rubia cordifolia* (Rubia cordifolia leaf), *Platycladus orientalis* (Platycladus orientalis leaf), and *Sanguisorba officinalis* (Sanguisorba officinalis) cool the blood and stop bleeding; *Paeonia lactiflora* (Red peony root) clears heat and cools the blood; *Nelumbo nucifera* (Lotus root node) is sweet and neutral, effectively stopping bleeding and removing blood stasis. These six herbs serve as adjuvant herbs. * The combined effects of these herbs, with their warming and cooling properties complementing each other, work together to nourish the liver and kidneys, replenish qi and yin, clear heat and stop bleeding.

[0025] In another specific embodiment, the traditional Chinese medicine preparation of the present invention is a capsule or granule.

[0026] Preferably, the traditional Chinese medicine preparation of the present invention is a capsule. Compared with traditional decoctions, traditional Chinese medicine capsules are more convenient to take and carry, and the active ingredients are more stable, the quality is easier to control, and the absorption is more efficient. However, when the capsule contents are too hygroscopic, it can not only cause the capsule contents to clump and stick together, but also cause the capsule shell to soften and deform. Therefore, optimizing the extraction process of traditional Chinese medicine extracts and pharmaceutical excipients is key to ensuring the stability of traditional Chinese medicine capsules.

[0027] On the one hand, in order to fully extract the active ingredients from the traditional Chinese medicine raw materials, this application first uses microwave extraction to extract the volatile oil active components from Platycladus orientalis leaves and Sanguisorba officinalis. Simultaneously, the extracted residue is refluxed with other traditional Chinese medicine raw materials using an ethanol-water solution to obtain other active components. Verification has shown that the active ingredients obtained by the extraction method of this application have the effects of tonifying the liver and kidneys, replenishing qi and nourishing yin, clearing heat and stopping bleeding, and can effectively prevent or treat chronic kidney disease.

[0028] Specifically, the preparation method of the volatile oil active ingredient is as follows: Weigh arborvitae leaves and Sanguisorba officinalis, pulverize them, and pass them through a 20-40 mesh sieve. Add diethyl ether for microwave extraction, filter, and set aside the filter residue. Combine the filtrates and centrifuge at 5000-8000 rpm for 5-15 minutes. Take the supernatant and remove the diethyl ether using a rotary evaporator to obtain a yellow volatile oil. Since the volatile oil itself is easily lost during storage and can also have an adverse effect on the capsule shell, this application first uses β-cyclodextrin to prepare an inclusion complex of the volatile oil before further preparing the capsules.

[0029] Preferably, in the above-mentioned method for preparing the active ingredients of volatile oil, the power of microwave extraction is 200-400W, the volume of ether added for each extraction is 2-5 times the total volume of Platycladus orientalis leaves and Sanguisorba officinalis, and the extraction is performed 1-3 times.

[0030] More preferably, the preparation method of the volatile oil inclusion complex is as follows: Dissolve the volatile oil in an appropriate amount of ethanol and set aside; weigh β-cyclodextrin at a mass ratio of volatile oil to β-cyclodextrin of 1:(1.8~2.4), add an appropriate amount of water, stir and heat until dissolved, then slowly add the ethanol solution containing the volatile oil, and stir at a constant temperature of 42℃~48℃ for 2.7h~3.2h; cool to room temperature, filter, wash the inclusion complex with water and anhydrous ethanol respectively, and dry at 40℃~50℃ to obtain the inclusion complex.

[0031] On the other hand, in order to improve the storage stability of capsules and ensure medication safety, this application also selected suitable excipients and formulation processes for specific traditional Chinese medicine extracts. The contents of the capsules consist of traditional Chinese medicine extracts and pharmaceutical excipients.

[0032] Studies have shown that, for the active ingredients of the traditional Chinese medicine in this application, when the mass ratio of the extracted extract to pregelatinized starch, microcrystalline cellulose, dicalcium phosphate and micronized silica gel is 1:(0.2-0.9):(0.15-0.6):(0.1-0.3):(0.01-0.04), the storage stability of the capsules is greatly improved.

[0033] In a second aspect of the invention, a method for preparing the traditional Chinese medicine preparation for the prevention or treatment of chronic kidney disease is provided.

[0034] In one specific embodiment, the preparation method of the traditional Chinese medicine preparation of the present invention includes the following steps:

[0035] (1) Weigh out the leaves of Platycladus orientalis and Sanguisorba officinalis, crush them and pass them through a 20-40 mesh sieve, add ether for microwave extraction, filter, and set aside the filter residue. Combine the filtrates and centrifuge at 5000-8000 rpm for 5-15 minutes. Take the supernatant and remove the ether with a rotary evaporator to obtain a yellow volatile oil. Then use β-cyclodextrin to prepare an inclusion complex for later use.

[0036] (2) Weigh out the following herbs: Ligustrum lucidum, Eclipta prostrata, Astragalus membranaceus, Codonopsis pilosula, Rehmannia glutinosa, Imperata cylindrica, Rubia cordifolia, Paeonia lactiflora, Nelumbo nucifera rhizome, and Glycyrrhiza uralensis. Crush them and add them to the residue from step (1). Then, reflux with 2-5 times the volume of 50-70% ethanol solution for 1-3 hours, repeating 1-3 times. Filter, combine the filtrates, and concentrate at 40℃-60℃ to 1.10-1.25 g / cm³ at room temperature. 3 The extract, for later use;

[0037] (3) Add the volatile oil inclusion complex, pregelatinized starch, microcrystalline cellulose and dicalcium phosphate from step (1) to the extract from step (2) to make a soft material. Extrude it through a 16-20 mesh to make wet granules. Dry it at 40℃~60℃ for 2~4 hours until the moisture content of the granules is ≤5%. Sieve it through a 20-30 mesh sieve to granulate it. Add micronized silica gel and mix well. Fill it into No. 0 capsules.

[0038] Preferably, the mass ratio of the extract, pregelatinized starch, microcrystalline cellulose, dicalcium phosphate and micronized silica is 1:(0.2-0.9):(0.15-0.6):(0.1-0.3):(0.01-0.04).

[0039] Preferably, in step (1), the power of microwave extraction is 200-400W, the volume of ether added each time is 2-5 times the total volume of arborvitae leaves and Sanguisorba officinalis, and the extraction is performed 1-3 times.

[0040] More preferably, the preparation method of the volatile oil inclusion complex is as follows: Dissolve the volatile oil in an appropriate amount of ethanol and set aside; weigh β-cyclodextrin at a mass ratio of volatile oil to β-cyclodextrin of 1:(1.8~2.4), add an appropriate amount of water, stir and heat until dissolved, then slowly add the ethanol solution containing the volatile oil, and stir at a constant temperature of 42℃~48℃ for 2.7h~3.2h; cool to room temperature, filter, wash the inclusion complex with water and anhydrous ethanol respectively, and dry at 40℃~50℃ to obtain the inclusion complex.

[0041] In a third aspect of the invention, the use of the traditional Chinese medicine preparation in the preparation of a medicament for the prevention or treatment of chronic kidney disease is provided.

[0042] This invention relates to a traditional Chinese medicine preparation used for symptoms such as lower back and knee pain, fatigue, dark yellow urine, hematuria, frequent urination, urgency, painful urination, five-center heat (palms, soles, and chest), and dry mouth caused by liver and kidney yin deficiency and blood heat. It has been used in over a thousand clinical cases. This preparation is significantly effective, safe to take, and no adverse reactions have been observed in humans to date.

[0043] Furthermore, the chronic kidney disease includes symptoms selected from those of lower back and knee pain, fatigue, dark yellow urine, hematuria, frequent urination, urgency, painful urination, hot flashes in the palms, soles, and / or dry mouth.

[0044] Compared with the prior art, the present invention has the following advantages:

[0045] (1) Research found that there are few similar treatments and effects on the market. The Chinese medicine formula in this application is reasonably matched, and the medicines complement each other, with warm and cool properties complementing each other, so as to tonify the liver and kidneys, replenish qi and nourish yin, clear heat and stop bleeding. It can effectively prevent or treat chronic kidney disease and improve the quality of life of the relevant population.

[0046] (2) The volatile oil in Platycladus orientalis leaves and Sanguisorba officinalis is one of their main active components. In order not to lose the active components of the volatile oil, the present invention uses microwave extraction to effectively extract the volatile oil in the two Chinese medicines and uses β-cyclodextrin for inclusion. This ensures that the loss of volatile oil during storage is reduced and does not have an adverse effect on the stability of the capsule shell.

[0047] (3) The Chinese medicine formula of the present invention has significant efficacy and is safe to take. It has no adverse reactions on the human body. Through the research on Chinese medicine extraction process and preparation process, compared with traditional decoction, it not only improves the efficacy, but also significantly improves the stability and disintegration time of the medicine, thereby increasing the patient's compliance with the medication. Detailed Implementation

[0048] The technical solution of the present invention will be described in more detail below with reference to specific embodiments. However, it should be understood that these embodiments are not intended to limit the scope of protection of the present invention.

[0049] Investigation of the preparation process of volatile oil inclusion compounds:

[0050] Dissolve the volatile oil in an appropriate amount of ethanol and set aside. Weigh β-cyclodextrin, add an appropriate amount of water, stir and heat until dissolved, then slowly add the ethanol solution containing the volatile oil dropwise, and stir at a constant temperature for a certain period of time. Cool to room temperature, filter, wash the inclusion complex with water and anhydrous ethanol respectively, and dry at 40°C to obtain the inclusion complex.

[0051] To obtain the optimal process, a three-factor, three-level experimental design was conducted, with the mass ratio of volatile oil to β-cyclodextrin (factor A), inclusion temperature (factor B), and inclusion time (factor C) as the factors to be investigated. The factor level table is shown in Table 1 below.

[0052] Table 1 Factor Level Table

[0053]

[0054] Based on the above factor levels, an orthogonal experimental design was adopted, and the inclusion rate and yield of the prepared inclusion complexes were determined. The results are shown in Table 2 below.

[0055] Table 2 Results of Orthogonal Experimental Design

[0056]

[0057] Based on the process conditions examined at the factor levels and in combination with the actual situation of the inclusion process, the optimal process conditions for the inclusion of volatile oil in this application are determined to be: a mass ratio of volatile oil to β-cyclodextrin of 1:(1.8~2.4), an inclusion temperature of 42℃~48℃, and an inclusion time of 2.7h~3.2h.

[0058] Example 1:

[0059] The composition of the Chinese medicinal materials by weight is as follows: Ligustrum lucidum 85.7 parts, Eclipta prostrata 85.7 parts, Astragalus membranaceus 214.3 parts, Codonopsis pilosula 142.9 parts, Rehmannia glutinosa 107.1 parts, Imperata cylindrica 142.9 parts, Rubia cordifolia 71.4 parts, Platycladus orientalis 85.7 parts, Sanguisorba officinalis 107.1 parts, Paeonia lactiflora 85.7 parts, Nelumbo nucifera rhizome 107.1 parts, and Glycyrrhiza uralensis 71.4 parts.

[0060] Preparation method: (1) Weigh the leaves of Platycladus orientalis and Sanguisorba officinalis, crush them and pass them through a 30-mesh sieve. Add 3 times the volume of diethyl ether and microwave extract at 350W. Filter. Add 3 times the volume of diethyl ether to the filter residue and microwave extract at 350W. Filter. Combine the filtrates and centrifuge at 8000rpm for 6 minutes. Take the supernatant and remove the diethyl ether using a rotary evaporator to obtain yellow volatile oil. Dissolve the volatile oil in an appropriate amount of ethanol. Weigh β-cyclodextrin at a mass ratio of volatile oil to β-cyclodextrin of 1:2. Add an appropriate amount of water, stir and heat until dissolved, and then... Slowly, an ethanol solution containing volatile oil was stirred at 46°C for 3 hours, cooled to room temperature, filtered, and the inclusion complex was washed with water and anhydrous ethanol, and dried at 40°C to obtain the inclusion complex powder; (2) Ligustrum lucidum, Eclipta prostrata, Astragalus membranaceus, Codonopsis pilosula, Rehmannia glutinosa, Imperata cylindrica, Rubia cordifolia, Paeonia lactiflora, Nelumbo nucifera rhizome and Glycyrrhiza uralensis were weighed, pulverized, added to the filter residue in step (1), and then extracted by reflux with 4 times the volume of 70% ethanol solution for 3 hours, repeated twice, filtered, the filtrates were combined, and concentrated at 50°C to 1.18 g / cm³ at room temperature. 3(2) The extract is prepared for use; (3) The volatile oil inclusion complex, pregelatinized starch, microcrystalline cellulose and dicalcium phosphate from step (1) are added to the extract from step (2) to make a soft material, which is then extruded through a 20-mesh sieve to form wet granules. The granules are dried at 40°C for 3 hours until the moisture content of the granules is ≤5%. The granules are then sieved through a 30-mesh sieve, mixed with microcrystalline silica gel, and filled into No. 0 capsules to obtain Chinese medicine capsules. The mass ratio of Chinese medicine extract, pregelatinized starch, microcrystalline cellulose, dicalcium phosphate and microcrystalline silica gel is 1:0.4:0.3:0.2:0.02.

[0061] Example 2:

[0062] The raw materials of the Chinese medicine are composed of the following parts by weight: 90 parts of Ligustrum lucidum, 90 parts of Eclipta prostrata, 220 parts of Astragalus membranaceus, 130 parts of Codonopsis pilosula, 100 parts of Rehmannia glutinosa, 130 parts of Imperata cylindrica, 60 parts of Rubia cordifolia, 90 parts of Platycladus orientalis, 110 parts of Sanguisorba officinalis, 90 parts of Paeonia lactiflora, 110 parts of Nelumbo nucifera rhizome, and 60 parts of Glycyrrhiza uralensis.

[0063] Preparation method: (1) Weigh the leaves of Platycladus orientalis and Sanguisorba officinalis, crush them and pass them through a 20-mesh sieve. Add 2 times the volume of diethyl ether and microwave extract at 250W. Filter. Add 2 times the volume of diethyl ether to the filter residue and microwave extract at 250W. Filter. Combine the filtrates and centrifuge at 6000rpm for 15 minutes. Take the supernatant and remove the diethyl ether using a rotary evaporator to obtain yellow volatile oil. Dissolve the volatile oil in an appropriate amount of ethanol. Weigh β-cyclodextrin at a mass ratio of volatile oil to β-cyclodextrin of 1:2.4. Add an appropriate amount of water, stir and heat until dissolved, and then... Slowly stir the ethanol solution containing volatile oil at 43℃ for 2.8h, cool to room temperature, filter, wash the inclusion complex with water and anhydrous ethanol respectively, dry at 50℃ to obtain inclusion complex powder; (2) Weigh the following herbs: Ligustrum lucidum, Eclipta prostrata, Astragalus membranaceus, Codonopsis pilosula, Rehmannia glutinosa, Imperata cylindrica, Rubia cordifolia, Paeonia lactiflora, Nelumbo nucifera and Glycyrrhiza uralensis, crush them, add the filter residue from step (1), then reflux with 3 times the volume of 65% ethanol solution for 2 hours, repeat twice, filter, combine the filtrates, concentrate at 60℃ to 1.21g / cm³ at room temperature. 3 (2) The extract is prepared for use; (3) The volatile oil inclusion complex, pregelatinized starch, microcrystalline cellulose and dicalcium phosphate from step (1) are added to the extract from step (2) to make a soft material. The material is extruded through an 18-mesh sieve to form wet granules. The granules are dried at 40°C for 4 hours until the moisture content of the granules is ≤5%. The granules are sieved through a 20-mesh sieve, mixed with microcrystalline silica gel, and filled into No. 0 capsules to obtain traditional Chinese medicine capsules. The mass ratio of traditional Chinese medicine extract, pregelatinized starch, microcrystalline cellulose, dicalcium phosphate and microcrystalline silica gel is 1:0.8:0.25:0.15:0.04.

[0064] Example 3:

[0065] The raw materials of the Chinese medicine are composed of the following parts by weight: 60 parts of Ligustrum lucidum, 60 parts of Eclipta prostrata, 200 parts of Astragalus membranaceus, 120 parts of Codonopsis pilosula, 80 parts of Rehmannia glutinosa, 120 parts of Imperata cylindrica, 60 parts of Rubia cordifolia, 60 parts of Platycladus orientalis, 140 parts of Sanguisorba officinalis, 60 parts of Paeonia lactiflora, 140 parts of Nelumbo nucifera rhizome, and 60 parts of Glycyrrhiza uralensis.

[0066] Preparation method: (1) Weigh the leaves of Platycladus orientalis and Sanguisorba officinalis, crush them and pass them through a 20-mesh sieve. Add 3 times the volume of diethyl ether and microwave extract at 400W. Filter. Add 3 times the volume of diethyl ether to the filter residue and microwave extract at 400W. Filter. Combine the filtrates and centrifuge at 7000rpm for 9 minutes. Take the supernatant and remove the diethyl ether using a rotary evaporator to obtain yellow volatile oil. Dissolve the volatile oil in an appropriate amount of ethanol. Weigh β-cyclodextrin at a mass ratio of volatile oil to β-cyclodextrin of 1:1.8. Add an appropriate amount of water, stir and heat until dissolved, and then... Slowly stir the ethanol solution containing volatile oil at 48℃ for 3.2h, cool to room temperature, filter, wash the inclusion complex with water and anhydrous ethanol respectively, dry at 45℃ to obtain inclusion complex powder; (2) Weigh the following herbs: Ligustrum lucidum, Eclipta prostrata, Astragalus membranaceus, Codonopsis pilosula, Rehmannia glutinosa, Imperata cylindrica, Rubia cordifolia, Paeonia lactiflora, Nelumbo nucifera and Glycyrrhiza uralensis, crush them, add the filter residue from step (1), and then reflux with 5 times the volume of 50% ethanol solution for 3 hours, repeat twice, filter, combine the filtrates, and concentrate at 60℃ to 1.15g / cm³ at room temperature. 3 (2) The extract is prepared for use; (3) The volatile oil inclusion complex, pregelatinized starch, microcrystalline cellulose and dicalcium phosphate from step (1) are added to the extract from step (2) to make a soft material, which is then extruded through a 16-mesh sieve to form wet granules. The granules are dried at 60°C for 2 hours until the moisture content of the granules is ≤5%, and then granulated by passing through a 20-mesh sieve. Microcrystalline silica gel is added and mixed to obtain Chinese medicine granules. The mass ratio of Chinese medicine extract, pregelatinized starch, microcrystalline cellulose, dicalcium phosphate and microcrystalline silica gel is 1:0.9:0.4:0.1:0.03.

[0067] Experimental Example 1:

[0068] To verify the storage stability of the traditional Chinese medicine capsules in this application, accelerated and long-term stability tests were conducted on the capsules.

[0069] (1) Accelerated testing

[0070] The capsules prepared in Examples 1-3 were placed at a temperature of 40℃±2℃ and a relative humidity of 75%±5% for 6 months. During the experiment, samples were taken at the end of the 0th, 1st, 2nd, 3rd, and 4th months respectively, and the integrity of the capsule shell, the properties of the contents, the disintegration time, the volatile oil content, and the moisture content were tested. The experimental results are shown in Table 3.

[0071] Table 3 Results of Accelerated Test

[0072]

[0073] (2) Long-term test

[0074] The capsules prepared in Examples 1-3 were placed at a temperature of 25℃±2℃ and a relative humidity of 60%±10% for 24 months. Samples were taken at 0 months, 6 months, 9 months, 12 months, and 24 months, and the integrity of the capsule shell, the properties of the contents, the disintegration time, the volatile oil content, and the moisture content were tested. The experimental results are shown in Table 4.

[0075] Table 4 Results of Long-Term Trial

[0076]

[0077] The results show that the capsules prepared in Examples 1-3 of this invention, under accelerated and long-term testing conditions, all measured indicators are within the range of quality standards, indicating that the sample properties are stable and their shelf life can be stored at room temperature for at least two years.

[0078] Experimental Example 2:

[0079] This experiment verified the efficacy of the traditional Chinese medicine capsules of this invention in treating chronic kidney disease.

[0080] 1. Test subjects

[0081] Sixty-eight patients with chronic kidney disease were selected and randomly divided into the invention group and the control group, with 34 patients in each group. The general information of the subjects is shown in Table 5.

[0082] Table 5 General Information of Patients with Chronic Kidney Disease

[0083]

[0084] 2. Diagnostic criteria

[0085] The study subjects were diagnosed and selected according to the relevant diagnostic criteria for "asthenia" and "edema" in chronic kidney disease as outlined in the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs".

[0086] 1) Dampness and turbidity syndrome, the main symptom is heaviness and fatigue in the limbs, and the secondary symptoms are sticky feeling in the mouth, abdominal distension, soft and rapid pulse or slippery and rapid pulse, and thick and greasy tongue coating;

[0087] 2) Spleen and kidney qi deficiency syndrome, the main symptoms are fatigue and weakness, soreness and weakness of the waist and knees, and the secondary symptoms are abdominal distension, deep and thready pulse, pale tongue with teeth marks;

[0088] 3) Blood stasis syndrome, the main symptom is a dull complexion, the secondary symptoms are numbness of the limbs, a choppy or thready pulse, and a purplish-dark tongue or petechiae and ecchymosis.

[0089] Subjects who did not take their medication on time or were unable to be evaluated due to allergies were excluded.

[0090] 3. Administration method

[0091] Subjects in the invention group and the control group were given the traditional Chinese medicine capsules (4 capsules each time, 3 times a day) of Example 1 of this application and traditional decoction, respectively. Both groups were treated for 2 months. Preparation method of traditional decoction: Weigh the raw materials in Example 1, add water and decoct twice, filter, combine the filtrates, and take in two doses.

[0092] 4. Treatment Standards

[0093] In accordance with the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs," the treatment effects on the subjects were evaluated:

[0094] Significant efficacy: After treatment, the patient's clinical symptoms disappeared, and the BUN (blood urea nitrogen) clearance rate decreased by ≥30%, the Scr (endogenous serum creatinine) clearance rate decreased by ≥30%, or the Scr clearance rate increased by ≥30%;

[0095] Effective: BUN clearance rate decreased by ≥20%, Scr clearance rate decreased by 10%-29%, or Ccr (endogenous creatinine) clearance rate increased by ≥20%;

[0096] Ineffective: After treatment, the patient's clinical symptoms, BUN, Scr and Ccr clearance rates did not improve significantly or even worsened.

[0097] 5. Test Results

[0098] Table 6. Comparison of clinical efficacy results between the invention group and the control group (n=34)

[0099]

[0100] Table 7. Renal function results before and after treatment in the invention group and the control group (n=34)

[0101]

[0102] The results showed that, compared with traditional decoction treatment, the herbal capsules of the present invention can significantly alleviate renal function and clinical symptoms of chronic kidney disease, and have good safety with no adverse reactions found. They can be used for the prevention and treatment of chronic kidney disease.

Claims

1. A traditional Chinese medicine preparation for the prevention or treatment of chronic kidney disease, characterized in that, The active ingredients of the traditional Chinese medicine preparation are made from the following parts by weight of traditional Chinese medicine raw materials: 50-120 parts of Ligustrum lucidum, 50-120 parts of Eclipta prostrata, 180-250 parts of Astragalus membranaceus, 100-180 parts of Codonopsis pilosula, 60-150 parts of Rehmannia glutinosa, 100-180 parts of Imperata cylindrica, 40-110 parts of Rubia cordifolia, 50-120 parts of Platycladus orientalis, 60-150 parts of Sanguisorba officinalis, 50-120 parts of Paeonia lactiflora, 60-150 parts of Nelumbo nucifera rhizome, and 40-110 parts of Glycyrrhiza uralensis.

2. The traditional Chinese medicine preparation as described in claim 1, characterized in that, The active ingredients of the traditional Chinese medicine preparation are made from the following parts by weight of traditional Chinese medicine raw materials: 68-100 parts of Ligustrum lucidum, 68-100 parts of Eclipta prostrata, 195-225 parts of Astragalus membranaceus, 120-160 parts of Codonopsis pilosula, 80-120 parts of Rehmannia glutinosa, 120-160 parts of Imperata cylindrica, 55-95 parts of Rubia cordifolia, 68-100 parts of Platycladus orientalis, 80-120 parts of Sanguisorba officinalis, 68-100 parts of Paeonia lactiflora, 80-120 parts of Nelumbo nucifera rhizome, and 55-95 parts of Glycyrrhiza uralensis.

3. The traditional Chinese medicine preparation as described in claim 2, characterized in that, The active ingredients of the traditional Chinese medicine preparation are made from the following parts by weight of traditional Chinese medicine raw materials: 85.7 parts of Ligustrum lucidum, 85.7 parts of Eclipta prostrata, 214.3 parts of Astragalus membranaceus, 142.9 parts of Codonopsis pilosula, 107.1 parts of Rehmannia glutinosa, 142.9 parts of Imperata cylindrica, 71.4 parts of Rubia cordifolia, 85.7 parts of Platycladus orientalis, 107.1 parts of Sanguisorba officinalis, 85.7 parts of Paeonia lactiflora, 107.1 parts of Nelumbo nucifera rhizome, and 71.4 parts of Glycyrrhiza uralensis.

4. The traditional Chinese medicine preparation according to any one of claims 1 to 3, characterized in that, The traditional Chinese medicine preparation is a capsule or granule, and the contents of the capsule are composed of traditional Chinese medicine extracts and pharmaceutical excipients.

5. The traditional Chinese medicine preparation as described in claim 4, characterized in that, The pharmaceutical excipients comprise pregelatinized starch, microcrystalline cellulose, dicalcium phosphate, and micronized silica in a mass ratio of (0.2–0.9):(0.15–0.6):(0.1–0.3):(0.01–0.04).

6. The method for preparing a traditional Chinese medicine preparation according to any one of claims 1 to 5, characterized in that, The method includes the following steps: (1) Weigh out the leaves of Platycladus orientalis and Sanguisorba officinalis, crush them and pass them through a 20-40 mesh sieve, add ether for microwave extraction, filter, and set aside the filter residue. Combine the filtrates and centrifuge at 5000-8000 rpm for 5-15 minutes. Take the supernatant and remove the ether with a rotary evaporator to obtain a yellow volatile oil. Then use β-cyclodextrin to prepare an inclusion complex for later use. (2) Weigh out the following herbs: Ligustrum lucidum, Eclipta prostrata, Astragalus membranaceus, Codonopsis pilosula, Rehmannia glutinosa, Imperata cylindrica, Rubia cordifolia, Paeonia lactiflora, Nelumbo nucifera rhizome, and Glycyrrhiza uralensis. Crush them and add them to the residue from step (1). Then, reflux with 2-5 times the volume of 50-70% ethanol solution for 1-3 hours, repeating 1-3 times. Filter, combine the filtrates, and concentrate at 40℃-60℃ to 1.10-1.25 g / cm³ at room temperature. 3 The extract, for later use; (3) Add the volatile oil inclusion complex, pregelatinized starch, microcrystalline cellulose and dicalcium phosphate from step (1) to the extract from step (2) to make a soft material. Extrude it through a 16-20 mesh to make wet granules. Dry it at 40℃~60℃ for 2~4 hours until the moisture content of the granules is ≤5%. Sieve it through a 20-30 mesh sieve to granulate it. Add micronized silica gel and mix well. Fill it into No. 0 capsules.

7. The preparation method according to claim 6, characterized in that, The mass ratio of the extract, pregelatinized starch, microcrystalline cellulose, dicalcium phosphate, and micronized silica gel is 1:(0.2-0.9):(0.15-0.6):(0.1-0.3):(0.01-0.04).

8. The preparation method according to claim 7, characterized in that, In step (1), the power of microwave extraction is 200-400W, and the volume of ether added each time is 2-5 times the total volume of arborvitae leaves and Sanguisorba officinalis. Extraction is performed 1-3 times. The preparation method of the volatile oil inclusion complex is as follows: Dissolve the volatile oil in an appropriate amount of ethanol and set aside; weigh β-cyclodextrin at a mass ratio of volatile oil to β-cyclodextrin of 1:(1.8~2.4), add an appropriate amount of water, stir and heat until dissolved, then slowly add the ethanol solution containing the volatile oil dropwise, and stir at a constant temperature of 42℃~48℃ for 2.7h~3.2h; cool to room temperature, filter, wash the inclusion complex with water and anhydrous ethanol respectively, and dry at 40℃~50℃ to obtain the inclusion complex.

9. The use of the traditional Chinese medicine preparation as described in any one of claims 1 to 5 in the preparation of a medicament for the prevention or treatment of chronic kidney disease.

10. The application as described in claim 9, characterized in that, The chronic kidney disease is characterized by symptoms selected from those of lower back and knee pain, fatigue, dark yellow urine, hematuria, frequent urination, urgency, painful urination, hot flashes in the palms, soles, and / or dry mouth.

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