Traditional Chinese medicine composition for treating renal bone diseases as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating renal bone diseases and a preparation method and application thereof. The composition consists of the following components in parts by weight: 5-30 parts of herba epimedii, 5-30 parts of astragalus membranaceus, 1-12 parts of raw rhubarb, 3-20 parts of bighead atractylodes rhizome and 1-15 parts of fructus piperis longi. Based on the pathogenesis of deficiency, cold, blood stasis and stagnation cementation of renal bone diseases, a synergistic formula of four methods of warming yang, tonifying qi, dispersing blood stasis and relaxing bowels is created for the first time, the whole formula has the characteristics of simultaneous use of cold and warm, simultaneous regulation of ascending and descending and simultaneous application of dredging and tonifying, and the effects of dispelling haze when kidney yang is recovered, eliminating dampness and turbidity when spleen qi is strengthened, regulating qi of the bowels when stasis is dredged and finally harmonizing qi, blood, yin and yang are achieved. The unique characteristics of various traditional Chinese medicines are ingeniously fused, and the complementary and synergistic treatment effect is achieved. The traditional Chinese medicine composition is safe, reliable and remarkable in curative effect, and has wide clinical application potential in the field of treatment of renal bone diseases.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition for treating renal osteodystrophy, its preparation method, and its application. Background Technology

[0002] Chronic kidney disease (CKD) is a global health problem with an incidence rate of approximately 10%. Renal osteodystrophy (ROD), also known as chronic kidney disease-mineral bone metabolism disorder (CKD-MBD), is a serious complication of CKD and a major cause of disability and death among CKD patients. ROD can appear in the early stages of CKD; when the glomerular filtration rate (GFR) is less than 50%, half of the patients will develop pathological changes. By the end stage of CKD, almost 100% of patients will develop renal osteodystrophy. The pathological characteristic of renal osteodystrophy is the imbalance of bone minerals caused by CKD, leading to bone damage and reduced bone mass, resulting in fractures that severely impact patients' quality of life and increase the risk of death. Furthermore, fractures place a significant economic burden on the healthcare system. Current Western medicine treatments primarily focus on symptom relief, such as controlling blood phosphorus, regulating blood calcium, administering calcium receptor agonists, and performing hemodialysis and parathyroidectomy. However, these methods only provide temporary relief and have poor long-term efficacy. Therefore, developing new methods and means to effectively prevent and treat renal osteodystrophy is of great significance for improving patient prognosis and reducing the medical burden.

[0003] Traditional Chinese medicine (TCM) has demonstrated certain efficacy and advantages in the treatment of renal osteodystrophy. In the prior art, patent CN119700858A reports the application of a TCM composition in the preparation of a drug for treating and / or preventing renal osteodystrophy. This TCM composition includes Panax notoginseng, Ligusticum chuanxiong, Corydalis yanhusuo, Paeonia lactiflora, Achyranthes bidentata, Cibotium barometz, Rheum palmatum, and Angelica pubescens. This TCM composition can significantly improve impaired renal function and calcium and phosphorus metabolism; effectively increase bone mineral density; and increase the expression level of BMP-7 protein in bone tissue, thus improving renal osteodystrophy.

[0004] Many ancient Chinese medical texts have also elucidated the pathological mechanisms of renal osteodystrophy. For example, the *Huangdi Neijing Suwen* states, "The five viscera govern: the heart governs the vessels, the lungs govern the skin, the liver governs the tendons, the spleen governs the flesh, and the kidneys govern the bones," thus proposing the theory that "the kidneys govern the bones." Furthermore, the *Suwen* states, "The kidneys govern the bones and produce marrow," and the *Medical Classics* records, "There is marrow within the bones; bones are produced from marrow… The kidneys store essence, and essence produces marrow; therefore, bones are where the kidneys reside." Both texts illustrate that skeletal growth and development depend on the nourishment of "kidney essence," suggesting an intrinsic relationship between "kidney – essence – marrow – bone." Abundant kidney essence generates bone marrow, nourishes the bones, and promotes their growth. For example, the *Suwen* (Plain Questions) chapter on *Wei Lun* (Treatise on Atrophy) states: "The kidney governs the bone marrow of the body... When bones wither and marrow diminishes, bone atrophy occurs." Traditional Chinese medicine believes that renal osteodystrophy is caused by the deficiency of kidney essence, which fails to generate marrow, leading to mineral and bone metabolism disorders due to insufficient nourishment of the bones. Therefore, it is categorized under "bone atrophy," "bone fistula," "asthenia," and "bone arthralgia." Based on its manifestation in the bones and its root cause in the kidneys, its connection to the liver and spleen, and the presence of blood stasis and turbid toxins, the pathogenesis of renal osteodystrophy is considered to be due to various etiologies leading to the deficiency of kidney essence, which fails to generate marrow, resulting in insufficient nourishment of the bones and causing mineral and bone metabolism disorders or osteoporosis. The TCM syndromes of renal osteodystrophy are related to spleen and kidney yang deficiency, qi deficiency, and blood stasis, with spleen and kidney yang deficiency and blood stasis being the most common characteristics. Common clinical features of patients with spleen and kidney yang deficiency include advanced age, aversion to cold, fatigue, and abnormal parathyroid hormone levels.

[0005] Therefore, by adhering to the principle of treating bone diseases by addressing the kidneys, and applying traditional Chinese medicine formulas with effects such as tonifying the kidneys, promoting blood circulation, and strengthening bones, it is hoped that kidney function can be improved, abnormal bone metabolism can be regulated, secondary hyperparathyroidism can be alleviated, and the quality of life and prognosis of ROD patients can be improved. Summary of the Invention

[0006] In view of this, this invention is based on the pathogenesis of renal osteodystrophy, which is characterized by the combination of "deficiency-cold-stasis-stagnation". It is the first to create a formula that combines four methods: "warming yang, tonifying qi, resolving stasis, and unblocking the bowels". The whole formula is characterized by the use of both cold and warm, the simultaneous regulation of ascending and descending, and the combination of unblocking and tonifying. It achieves the effect of "when kidney yang is restored, yin and yang are dispelled; when spleen qi is healthy, dampness and turbidity are transformed; when stasis is cleared, bowel qi is regulated", and finally achieves the effect of harmonizing qi, blood, yin and yang, thereby effectively treating renal osteodystrophy.

[0007] One of the objectives of this invention is to provide a traditional Chinese medicine composition for treating renal osteodystrophy.

[0008] To achieve the above objectives, the present invention adopts the following technical solution:

[0009] A traditional Chinese medicine composition for treating renal osteodystrophy, the composition comprising the following components in parts by weight: Epimedium 5-30 parts, Astragalus membranaceus 5-30 parts, Rheum palmatum 1-12 parts, Atractylodes macrocephala 3-20 parts, and Piper longum 1-15 parts.

[0010] This invention's traditional Chinese medicine composition is based on the pathogenesis of deficiency, cold, blood stasis, and stagnation. It uses Epimedium, which is pungent, sweet, and hot, directly tonifying the true fire of the kidneys, as the chief herb. This allows the fire to generate energy and strengthen the earth element, both warming the kidney yang to nourish the extremities and transforming the spleen earth to transport food and water, thus simultaneously warming yang, resolving dampness, and promoting blood circulation. Astragalus, sweet and warm, is purely yang, greatly tonifying the qi of the spleen and lungs. Its qi acts as the commander of blood, assisting Epimedium in raising yang qi and distributing essence to the three jiaos, while also promoting blood circulation to eliminate stagnation. Furthermore, it strengthens the interior and consolidates the exterior, preventing external pathogens from re-entering the body. Therefore, it is the assistant herb. Atractylodes macrocephala, bitter, warm, and sweet, is stabilizing and does not disperse, specifically entering the middle jiao, drying dampness, strengthening the spleen, and consolidating the earth element to prevent water retention. Combined with Astragalus, its qi-tonifying and clearing effects are doubled; combined with Epimedium, it promotes the mutual generation of fire and earth, resulting in endless transformation. Therefore, it is the adjuvant herb. However, prolonged spleen and kidney yang deficiency inevitably leads to cold stagnation. When stagnation and turbidity occur, and the bowel function is obstructed, pathogenic factors have no way to escape. Therefore, the bitter, cold, and potent raw rhubarb is added as a counteracting agent. Its power to break through the obstruction and expel cold accumulations and promote the elimination of the old and new, allowing stagnation to be expelled through the stool. Moreover, bitterness can strengthen yin, and coldness can restrain warmth, preventing the dryness and stagnation of warming medicines from damaging yin. Furthermore, the pungent, hot, and aromatic Piper longum is added to warm the kidneys, dispel cold, promote qi circulation, and relieve pain. It not only assists the principal medicine in strengthening yang to dispel stagnation, but also assists rhubarb in clearing the bowels without causing damage to the middle jiao due to its bitterness and coldness. Moreover, its pungent and aromatic properties can invigorate the spleen, open the stomach, and relieve bloating and fullness. The entire formula uses both cold and warm properties, regulates ascending and descending functions, and combines clearing and tonifying. It tonifies without causing stagnation, warms without causing dryness, and attacks without causing harm. When kidney yang is restored, stagnation and turbidity are dispelled; when spleen qi is strengthened, dampness and turbidity are transformed; and when stagnation is cleared, bowel function is regulated. Ultimately, it achieves the goal of transforming yang into qi, qi circulating blood, and blood carrying the spirit, thereby achieving the treatment of renal osteodystrophy.

[0011] Preferably, the traditional Chinese medicine composition comprises the following components in parts by weight: Epimedium 9-25 parts, Astragalus 9-30 parts, Rhubarb 3-12 parts, Atractylodes macrocephala 6-15 parts, and Piper longum 3-9 parts.

[0012] Preferably, the traditional Chinese medicine composition comprises the following components in parts by weight: 10-20 parts of Epimedium, 10-20 parts of Astragalus membranaceus, 3-6 parts of raw rhubarb, 6-15 parts of Atractylodes macrocephala, and 3-6 parts of Piper longum.

[0013] As a preferred embodiment, the traditional Chinese medicine composition comprises the following components in parts by weight: 10 parts Epimedium, 10 parts Astragalus, 6 parts Rhubarb, 6 parts Atractylodes macrocephala, and 3 parts Piper longum.

[0014] As a preferred embodiment, the traditional Chinese medicine composition comprises the following components in parts by weight: 20 parts of Epimedium, 20 parts of Astragalus membranaceus, 3 parts of raw rhubarb, 15 parts of Atractylodes macrocephala, and 6 parts of Piper longum.

[0015] The second objective of this invention is to provide a method for preparing traditional Chinese medicine preparations based on the aforementioned traditional Chinese medicine composition.

[0016] To achieve the above objectives, the present invention adopts the following technical solution:

[0017] The method for preparing traditional Chinese medicine preparations based on the aforementioned traditional Chinese medicine composition includes the following steps:

[0018] S1: Weigh each herb according to the prescription, add 8-20 times the amount of water, soak for 0.5-2 hours; bring to a boil over high heat, then simmer over low heat for 20-60 minutes, filter, and obtain the dregs and liquid.

[0019] S2: Add 5-20 times the amount of water to the dregs obtained in S1, bring to a boil over high heat, then simmer over low heat for 20-60 minutes. Filter out the decoction and combine it with the decoction obtained in S1 to obtain the Chinese medicine preparation.

[0020] As a preferred option, 10-12 times the amount of water is added to S1.

[0021] As a preferred option, in S1, soaking for 1 hour is performed.

[0022] As a preferred option, in S1, simmer over low heat for 30 minutes.

[0023] Preferably, in step S2, 10 times the amount of water is added to the dregs.

[0024] As a preferred option, in S2, simmer over low heat for 30 minutes.

[0025] The third objective of this invention is to provide a traditional Chinese medicine preparation prepared using the aforementioned method.

[0026] The fourth objective of this invention is to provide the application of the aforementioned traditional Chinese medicine composition and / or the aforementioned traditional Chinese medicine preparation in the preparation of a medicament for treating renal osteodystrophy.

[0027] To achieve the above objectives, the present invention adopts the following technical solution:

[0028] The use of the aforementioned traditional Chinese medicine composition and / or the aforementioned traditional Chinese medicine preparation in the preparation of a drug for treating renal osteodystrophy.

[0029] Preferably, the traditional Chinese medicine composition and / or the traditional Chinese medicine preparation are used in the preparation of a medicine for treating chronic kidney disease with spleen and kidney yang deficiency.

[0030] Preferably, the renal osteodystrophy is characterized by deficiency, cold, blood stasis, and stagnation, and the traditional Chinese medicine composition achieves the treatment of renal osteodystrophy through the synergistic effects of warming yang, tonifying qi, resolving blood stasis, and clearing the bowels.

[0031] Preferably, the traditional Chinese medicine composition and / or the traditional Chinese medicine preparation are used in the preparation of a medicine having one or more of the following effects (1)-6):

[0032] 1) Reduce serum creatinine, blood urea nitrogen, and / or cystatin C levels;

[0033] 2) Improve renal pathological damage, including reducing renal inflammatory infiltration, interstitial fibrosis and / or tissue calcification;

[0034] 3) Increase blood calcium levels and / or decrease blood phosphorus levels in patients with renal osteodystrophy;

[0035] 4) Increase bone metabolism levels, including increasing 1,25(OH)2D3 and / or OC levels;

[0036] 5) Improve bone pathological damage, including reducing bone marrow cavity fat cells, reducing trabecular bone fractures and / or increasing bone mineralization;

[0037] 6) Improve bone ultrastructural damage, including increasing bone mineral density, percentage bone mass, bone surface density, number of trabeculae, trabecular bone thickness and / or cortical bone thickness of the femur, and reducing trabecular separation.

[0038] The fifth objective of this invention is to provide an application of the aforementioned traditional Chinese medicine composition in combination with Western medicine in the preparation of a drug for treating renal osteodystrophy characterized by deficiency, cold, blood stasis, and stagnation.

[0039] To achieve the above objectives, the present invention adopts the following technical solution:

[0040] The aforementioned traditional Chinese medicine composition, in combination with Western medicine, is used in the preparation of a drug for treating renal osteodystrophy characterized by deficiency, cold, blood stasis, and stagnation. The Western medicine includes any one or more of the following: calcium-containing phosphate binders, calcium-free phosphate binders, active vitamin D3, and calcimimetic agents.

[0041] Preferably, the calcium-containing phosphorus binder includes one or more of calcium carbonate and calcium acetate; the calcium-free phosphorus binder includes one or more of lanthanum carbonate and sevelamer tablets; the active vitamin D3 includes calcitriol; and the calcium mimicry agent includes cinacalcet.

[0042] The beneficial effects of this invention are as follows:

[0043] 1. This invention provides a traditional Chinese medicine composition based on the "deficiency-cold-stasis-stagnation" pathogenesis of renal osteodystrophy. The composition contains Epimedium, Astragalus, Rhubarb, Atractylodes macrocephala and Piper longum. Through the synergistic effects of warming yang, tonifying qi, removing blood stasis and clearing the bowels, it achieves effective treatment of renal osteodystrophy.

[0044] 2. The traditional Chinese medicine composition of the present invention can significantly improve renal function in mice with renal osteodystrophy, including reducing serum creatinine, blood urea nitrogen, and cystatin C levels, alleviating renal pathological damage, improving blood calcium and phosphorus metabolism, increasing bone metabolism, and improving bone pathology and ultrastructural damage. These results indicate that the traditional Chinese medicine composition has significant therapeutic effects in treating renal osteodystrophy.

[0045] 3. In clinical trials on patients with chronic kidney disease of the spleen and kidney yang deficiency type, the traditional Chinese medicine composition of the present invention showed significant efficacy, with the total effective rate of the treatment group reaching 83.33%, far higher than that of the control group (61.29%). In addition, the treatment group showed significant advantages in reducing serum urea nitrogen, serum creatinine and phosphorus levels, and increasing calcium levels, without obvious toxic side effects.

[0046] 4. This invention provides a method for preparing a traditional Chinese medicine composition, which extracts the effective components of traditional Chinese medicine through decoction. The method is simple and easy to implement, and is suitable for large-scale production and clinical application.

[0047] 5. The traditional Chinese medicine composition of this invention can also be used in combination with existing Western medicine treatment regimens to improve the overall therapeutic effect. This invention provides more treatment options for patients with chronic kidney disease of the spleen and kidney yang deficiency type. Attached Figure Description

[0048] Figure 1 The figure shows the results of detecting the effect of the traditional Chinese medicine composition on renal function (mean±sd) in mice with renal osteodystrophy (n=5, compared with the Model group, *P < 0.05, **P < 0.01; compared with the Control group, ##P < 0.01); among which, Figure 1 -A is a graph showing the effect of a traditional Chinese medicine composition on serum creatinine in mice with renal osteodystrophy; Figure 1 -B is a graph showing the effect of traditional Chinese medicine composition on serum urea nitrogen in mice with renal osteodystrophy; Figure 1 -C is the effect of the traditional Chinese medicine composition on serum cystatin C in mice with renal osteodystrophy.

[0049] Figure 2 Figure 1 shows the results of HE and Masson staining to detect the effect of traditional Chinese medicine composition on renal pathological damage in mice with renal osteodystrophy.

[0050] Figure 3 The figure shows the results of detecting the effect of traditional Chinese medicine composition on blood calcium and phosphorus in mice with renal osteodystrophy (n=5, compared with the Model group, *P < 0.05, **P < 0.01; compared with the Control group, ##P < 0.01); among which, Figure 3 -A is a graph showing the effect of a traditional Chinese medicine composition on serum calcium in mice with renal osteodystrophy; Figure 3 -B is the effect of the traditional Chinese medicine composition on serum phosphorus in mice with renal osteodystrophy.

[0051] Figure 4 The figure shows the results of detecting the effect of traditional Chinese medicine composition on bone metabolism levels in mice with renal osteodystrophy (n=5, **P < 0.01 compared with the Model group; #P < 0.05 compared with the Control group); among which, Figure 4-A is the effect of the traditional Chinese medicine composition on the blood level of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in mice with renal osteodystrophy; Figure 4 -B is a graph showing the effect of a traditional Chinese medicine composition on osteocalcin (OC) in the blood of mice with renal osteodystrophy.

[0052] Figure 5 Figure showing the results of HE and Goldner staining to detect the effects of traditional Chinese medicine composition on bone pathology in mice with renal osteodystrophy.

[0053] Figure 6 This is a micro-CT three-dimensional reconstruction image showing the effect of a traditional Chinese medicine composition on the bones of mice with renal osteodystrophy.

[0054] Figure 7 CT parameter maps showing the effects of traditional Chinese medicine composition on bone in mice with renal osteodystrophy (n=5, *P < 0.05, **P < 0.01 compared with the Model group; #P < 0.05, ##P < 0.01 compared with the Control group); among which, Figure 7 -A is a graph showing the effect of the traditional Chinese medicine composition on the bone mineral density of the femur in mice with renal osteodystrophy; Figure 7 -B is a graph showing the effect of the traditional Chinese medicine composition on the percentage bone mass of the femur in mice with renal osteodystrophy; Figure 7 -C is the effect of the traditional Chinese medicine composition on the surface density of the femur in mice with renal osteodystrophy; Figure 7 -D is a graph showing the effect of the traditional Chinese medicine composition on the trabecular bone thickness of the femur in mice with renal osteodystrophy; Figure 7 -E is a graph showing the effect of the traditional Chinese medicine composition on the number of trabecular bones in the femur of mice with renal osteodystrophy; Figure 7 -F is a graph showing the effect of the traditional Chinese medicine composition on the trabecular separation of the femur in mice with renal osteodystrophy; Figure 7 -G is a graph showing the effect of a traditional Chinese medicine composition on the cortical bone thickness of the femur in mice with renal osteodystrophy. Detailed Implementation

[0055] The technical solution of the present invention will be described more clearly and completely below with reference to specific embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Therefore, based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the protection scope of the present invention.

[0056] This invention provides a traditional Chinese medicine composition for treating renal osteodystrophy, as detailed below:

[0057] A. Formula

[0058] By weight, it includes the following components: Epimedium 9-25 parts, Astragalus 9-30 parts, Rhubarb 3-12 parts, Atractylodes macrocephala 6-15 parts, Piper longum 3-9 parts.

[0059] B. Indications

[0060] Renal osteodystrophy, chronic kidney disease with spleen and kidney yang deficiency.

[0061] C. Solution

[0062] The entire formula is based on the pathogenesis of "deficiency-cold-stasis-stagnation," using Epimedium, which is pungent, sweet, and hot, to directly replenish the true fire of the kidneys, acting as the chief herb. This allows the fire to generate energy and the earth to be warmed, both by stimulating the kidney yang to warm the extremities and by transforming the spleen earth to transport food and water. In one fell swoop, it warms the yang, resolves dampness, and promotes blood circulation. Astragalus, which is sweet, warm, and pure yang, greatly replenishes the qi of the spleen and lungs. Taking advantage of the principle that "qi is the commander of blood," it not only helps Epimedium to raise yang qi and distribute essence to the three jiaos, but also promotes blood circulation to eliminate stagnation. Furthermore, it supports the interior and consolidates the exterior, preventing external pathogens from taking advantage of the deficiency. Therefore, it is the assistant herb. Atractylodes macrocephala, which is bitter, warm, and sweet, is stabilizing and does not move. It specifically enters the middle jiao, drying dampness, strengthening the spleen, and consolidating the earth to prevent water retention. It works in combination with Astragalus. The effect of invigorating qi and promoting the upward movement of clear qi is doubled. When combined with epimedium, fire and earth generate each other, creating endless transformations, hence it is used as an adjuvant. However, with prolonged deficiency of spleen and kidney yang, cold stagnation will inevitably be accompanied by stagnation and turbidity. If the bowel qi is obstructed, the evil will have no way out. Therefore, the bitter, cold and potent raw rhubarb is added as an adjuvant. Its "blocking the gates and seizing the door" power is used to clear away the cold accumulation and promote the elimination of the old and the new, so that the stagnation can be eliminated through the stool. Moreover, bitterness can strengthen yin and coldness can restrain warmth, preventing the dryness and heat of warm medicines from damaging yin. Furthermore, the pungent, hot and aromatic Piper longum is added to warm the kidneys, dispel cold, promote qi and relieve pain. It not only helps the chief medicine to strengthen yang and eliminate yin haze, but also assists rhubarb in clearing the bowels without causing the bitterness and coldness to damage the middle jiao. Moreover, the pungent and aromatic properties can awaken the spleen, open the stomach, and relieve bloating and fullness. The formula combines cold and heat, regulates ascending and descending, and combines tonification and purgation: it tonifies without causing stagnation, warms without causing dryness, and attacks without causing harm. When kidney yang is restored, yin stagnation dissipates; when spleen qi is strengthened, dampness and turbidity are transformed; and when stagnation is cleared, the qi of the internal organs is regulated. Ultimately, it achieves the goal of "yang transforming into qi, qi circulating through blood, and blood carrying the spirit."

[0063] In this embodiment of the invention, the preparation method of the traditional Chinese medicine composition for treating renal osteodystrophy includes:

[0064] Weigh each herb according to the prescription, add 10-12 times the amount of water, and soak for 1 hour; bring to a boil over high heat, then simmer over low heat for 30 minutes, and filter out the liquid for later use; add 10 times the amount of water to the dregs again, bring to a boil over high heat, then simmer over low heat for 30 minutes, filter out the liquid and combine it with the previous liquid to obtain the final product.

[0065] Example 1

[0066] A traditional Chinese medicine composition for treating renal osteodystrophy comprises the following components in parts by weight: 10 parts Epimedium, 10 parts Astragalus membranaceus, 6 parts Rheum palmatum, 6 parts Atractylodes macrocephala, and 3 parts Piper longum.

[0067] Example 2

[0068] A traditional Chinese medicine composition for treating renal osteodystrophy comprises the following components in parts by weight: 20 parts Epimedium, 20 parts Astragalus membranaceus, 3 parts Rheum palmatum, 15 parts Atractylodes macrocephala, and 6 parts Piper longum.

[0069] Comparative Example 1

[0070] The control group consisted of the following components by weight: 20 parts Epimedium and 20 parts Astragalus.

[0071] Example 3. Animal efficacy of combination drugs against renal osteodystrophy in mice.

[0072] 1. Animal grouping and administration

[0073] After one week of feeding, C57BL / 6 mice were divided into 5 groups (AE), with 10 mice in each group. Except for the normal group (Group A), all BF groups underwent 5 / 6 nephrectomy and were fed a high-phosphorus diet to establish a chronic kidney disease and bone metabolism disorder model. The Shenqi Yanshen Formula drug group (DE group): Starting from the first nephrectomy (day 0), mice were administered the combined drug solution of the corresponding doses from Example 1 (Drug-Low, 5.31 g crude drug / kg / d) and Example 2 (Drug-High, 9.71 g crude drug / kg / d) once daily by gavage for 8 weeks. The control group (Group C): Starting from the first nephrectomy (day 0), mice were administered the control drug solution (Comparsion, 6.06 g crude drug / kg / d) once daily by gavage. The model group (Group B) and the normal group (Group A) were administered the same amount of purified water by gavage for a total of 8 weeks.

[0074] 2. Obtain materials

[0075] After the last gavage in week 8 of the experiment, blood was collected from the ocular vein of the mice and they were euthanized. The mice were then placed on ice and the tissues were separated in sequence. The left kidney and the left and right hind limbs were removed.

[0076] (1) After the blood is allowed to stand, it is centrifuged at 3500 rpm / min for 10 min at 4℃ to separate the serum, which is then aliquoted into 1.5 mL centrifuge tubes and stored at -80℃ for subsequent detection of biochemical indicators or ELISA-related indicators.

[0077] (2) Five kidneys from each group were fixed in 4% paraformaldehyde, then embedded, sectioned and stained with HE and Masson staining to observe pathological changes.

[0078] (3) The left hind limb was directly fixed in 4% paraformaldehyde at 4°C for 24 hours. After 24 hours, the fixative was discarded, the femur was washed with PBS 3 times, and then placed in EDTA decalcification solution for decalcification. The decalcification solution was changed every 2 days. After decalcification, routine paraffin embedding and sectioning were performed, and then HE and Goldner staining were performed respectively. Five right hind limbs were taken from each group and directly fixed in 4% paraformaldehyde and then used for bone mass detection by Micro-CT.

[0079] 3. The therapeutic effect of the drug on renal osteodystrophy in mice.

[0080] (1) Improved serum creatinine, blood urea nitrogen and cystatin C in mice with renal osteodystrophy

[0081] Compared with the normal control group, the serum creatinine, blood urea nitrogen, and cystatin C levels in the model control group mice were significantly increased, indicating significant renal function impairment after modeling. Compared with the model control group, the serum creatinine, blood urea nitrogen, and cystatin C levels in both the low- and high-dose drug combination groups were significantly decreased. The high-dose group showed better improvement in serum creatinine, blood urea nitrogen, and cystatin C levels than the low-dose group, and both the low- and high-dose groups showed better effects than the control group. These results suggest that both the low- and high-dose drug combination groups have a significant protective effect on renal function in mice. (See attached results) Figure 1 .

[0082] (2) Improves renal pathological damage in mice with chronic renal osteodystrophy

[0083] Mouse kidneys were stained with HE and Masson staining to observe inflammatory infiltration and fibrosis. Results showed that the model group exhibited inflammatory infiltration (white hollow arrows), tissue calcification (black arrows), and interstitial fibrosis (black triangles) in the kidneys compared to the control group. After intervention with the combined drugs, both the low- and high-dose groups showed reduced inflammatory infiltration, fibrosis, and tissue calcification. The kidney pathological damage in the control drug groups was improved compared to the model group, but not as significantly as in the low- and high-dose combined drug groups. This suggests that the combined drugs can improve kidney pathological damage in mice with renal osteodystrophy. (See attached results). Figure 2 .

[0084] (3) Improves blood calcium and phosphorus metabolism in mice with renal osteodystrophy

[0085] Compared with the control group, the serum calcium level of mice in the chronic kidney disease and bone metabolism disorder model group was significantly decreased (P<0.01), and the serum phosphorus level was significantly increased (P<0.01). After 8 weeks of combined drug intervention, both the low-dose and high-dose groups improved the serum calcium and phosphorus levels in the chronic kidney disease and bone metabolism disorder model group (P<0.05), and the control drug group also improved the serum calcium and phosphorus levels in the renal osteodystrophy model group (P<0.05). Results are shown below. Figure 3 .

[0086] (4) Improves bone metabolism in mice with renal osteodystrophy

[0087] Vitamin D regulates bone mass primarily through its active form, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Therefore, in clinical practice, bone mass is often indirectly observed by detecting 1,25(OH)2D3 levels. Osteocalcin (OC) represents osteogenic status. Compared to the control group, the model group mice showed decreased 1,25(OH)2D3 levels and significantly lower levels of the osteogenic metabolic marker OC (P<0.05), indicating reduced bone mass in the mice. After combined drug intervention, both the low- and high-dose groups improved 1,25(OH)2D3 and OC levels in mice with renal osteodystrophy, but no significant improvement was observed in the control group. Figure 4 .

[0088] (5) Improves bone pathological damage in mice with renal osteodystrophy

[0089] In mice, trabecular bone lesions were observed using HE staining, and femoral mineralization changes were observed using Goldner staining. Results are as follows: Figure 5 The results showed that the model group exhibited increased adipocytes (red arrows), trabecular bone fractures, and reduced bone mineralization (black arrows) compared to the control group, indicating pathological damage to the femur and successful modeling. After intervention with the combined drugs, varying degrees of reduction in femoral pathological damage were observed. Compared to the chronic kidney disease and bone metabolism disorder model groups, the low and high drug administration groups showed reduced adipocytes in the medullary cavity, decreased trabecular bone fractures, and increased bone mineralization. These results suggest that the combined drug group improved femoral pathological damage in mice with renal osteodystrophy.

[0090] (6) Improves bone ultrastructural damage in mice with renal osteodystrophy

[0091] MicroCT scans of mouse femurs, followed by 3D reconstruction, revealed that compared to the control group, the model group mice showed significantly decreased bone mineral density (BMD), bone volume per unit volume (BV / TV), bone surface density (BS / TV), trabecular bone number (Tb.N), trabecular bone thickness (Tb.Th), and cortical bone thickness (Ct.Th), while exhibiting significantly increased trabecular bone separation (Tb.Sp) (P<0.01). Following combined drug intervention, compared to the model group, the high-dose administration group showed significantly lower levels of BMD, BV / TV, and BV / TV in the femur. S / TV, Tb.N, and Tb.Th all increased to varying degrees (P<0.05), while Tb.Sp decreased significantly (P<0.01), but none recovered to the corresponding levels in the control group. In the low-dose group, femoral BV / TV, BS / TV, and Tb.Th all increased to varying degrees compared to the model group (P<0.05), while other femoral-related parameters showed only a trend of improvement, but the differences were not statistically significant. The control group only significantly improved some femoral parameters in the model mice, such as BV / TV and Tb.Th. Overall, the low-dose combination drug group was less effective than the high-dose group in improving bone ultrastructural damage in mice with renal osteodystrophy. Results are shown in […]. Figure 6 and 7 .

[0092] Example 4. Clinical case of combination drugs for chronic kidney disease.

[0093] 1. Experimental Methods

[0094] (1) General Information

[0095] Sixty hospitalized patients with chronic kidney disease, meeting the K / DOQI diagnostic criteria for stage 3-5 chronic kidney disease, were selected and randomly divided into a control group and a treatment group, with 30 patients in each group. The syndrome type and syndrome score were based on the "Diagnosis, Syndrome Differentiation and Efficacy Evaluation of Chronic Renal Failure (Trial Scheme)" formulated by the Nephrology Branch of the China Association of Traditional Chinese Medicine. The syndrome type was limited to "Spleen and Kidney Yang Deficiency Syndrome," and its key diagnostic points are as follows:

[0096] Main symptoms: facial swelling, aversion to cold and cold limbs, shortness of breath and fatigue, poor appetite and abdominal distension, soreness and coldness in the lower back and knees, cold pain in the bones, and clear or scanty urination.

[0097] Secondary symptoms: pale or dark complexion, edema (especially below the waist), loose stools, pale and swollen tongue or with teeth marks, white and slippery tongue coating, and deep and slow or deep and weak pulse.

[0098] If a patient presents with ≥3 primary symptoms, ≥2 secondary symptoms, and whose tongue and pulse examinations are consistent with these symptoms, the diagnosis can be confirmed as spleen and kidney yang deficiency syndrome.

[0099] Symptom score: 0, 2, 4, and 6 points are awarded for none, mild, moderate, and severe symptoms respectively. A total score of ≥10 points is required for inclusion.

[0100] The inclusion criteria for this study were: Scr 133-707 umol / L, Ccr < 80 ml / min.

[0101] Patients were randomly divided into a control group and a treatment group: the control group consisted of 31 patients who received routine clinical treatment; the treatment group consisted of 30 patients who received the medication described in Example 1. There were no statistically significant differences in clinical data between the groups (P>0.05).

[0102] (2) Treatment plan

[0103] All groups received routine treatment: a low-salt, low-fat, low-phosphorus diet with high-quality protein (protein intake 0.6-0.8 kg / day), blood pressure control, and correction of acid-base imbalances, anemia, and electrolyte disturbances, plus Western medicine treatment. Western medicine treatment, based on the 2017 KDIGO Clinical Practice Guidelines for the management / control of serum calcium, serum phosphorus, and PTH, involved selecting appropriate medications (calcium-containing phosphate binders such as calcium carbonate and calcium acetate, calcium-free phosphate binders such as lanthanum carbonate and sevelamer tablets, active vitamin D3 such as calcitriol, and calcimimetic agents such as cinacalcet) to control serum calcium, serum phosphorus, and PTH respectively. The treatment group received the above treatment plus the combination of traditional Chinese medicine decoction from this patent, one dose daily, divided into three oral doses (morning, noon, and evening), 100 ml each time. After 8 weeks of medication, white blood cell creatinine, blood urea nitrogen, and other indicators were checked, and the patients' clinical symptoms were assessed.

[0104] (3) Efficacy evaluation criteria

[0105] The guidelines were formulated in accordance with the "Guiding Principles for Clinical Research on New Traditional Chinese Medicine Drugs for the Treatment of Chronic Renal Failure": Marked efficacy: Significant improvement in TCM clinical symptoms and signs, with a reduction of ≥75% in syndrome score; Effective: Improvement in TCM clinical symptoms and signs, with a reduction of <75% or ≥30% in syndrome score; Ineffective: No significant improvement in TCM clinical symptoms and signs, or even worsening, with a reduction of <30% in syndrome score.

[0106] 2. Experimental Results

[0107] (1) The clinical efficacy comparison between the two groups of patients after treatment is shown in Table 1.

[0108] Table 1. Comparison of clinical efficacy before and after treatment in the two groups

[0109]

[0110] (2) Comparison of Scr, BUN, Ca, and P levels before and after treatment in the two groups of patients

[0111] After treatment, the serum urea nitrogen, serum creatinine and phosphorus levels in the treatment group were significantly lower than those in the control group, while the calcium levels were significantly higher in the treatment group (P < 0.05), as detailed in Table 2.

[0112] Table 2. Comparison of Scr, BUN, Ca, and P levels before and after treatment in the two groups of patients ( ±s)

[0113]

[0114] Note: Compared with the same group before treatment, *<0.05, **<0.01; compared with the control group after treatment, #<0.05, ##<0.01.

[0115] The experimental results above show that the traditional Chinese medicine of this invention has a definite curative effect on treating renal osteodystrophy or chronic kidney disease with spleen and kidney yang deficiency, with an effective rate of over 83% and no toxic side effects. It is an innovation in the treatment of renal osteodystrophy or chronic kidney disease with spleen and kidney yang deficiency.

[0116] Example 5. Typical Case

[0117] (1) Wang, a 59-year-old female patient, was admitted to the hospital on March 12, 2023.

[0118] Chief complaint: Recurrent bone pain, soreness and weakness in the lower back and knees, accompanied by weakness in walking for 4 years, which worsened and was accompanied by lower limb twitching for 3 weeks.

[0119] Medical History Summary: Diagnosed with "chronic renal failure (CKD stage 4)" 4 years ago, the patient has been taking calcium carbonate and calcitriol orally for a long time, but bone pain has gradually worsened, especially in the lower back and knees, and is particularly severe at night and after activity, accompanied by cold limbs, fatigue, and weakness. Three weeks ago, decreased urine output after a cold significantly exacerbated the bone pain, and bilateral calf muscle spasms developed, making walking difficult and requiring assistance. Past Medical History: Hypertension for 15 years, chronic glomerulonephritis for 20 years.

[0120] Traditional Chinese Medicine Four Diagnostic Methods: Dark and puffy complexion, listless spirit, aversion to cold and curled-up posture, cold pain in the lower back and knees as if sitting in water, muscle twitching, nocturia 3-4 times, clear and copious, poor appetite and abdominal distension, loose stools; pale, swollen and dark tongue with teeth marks on the edges, white and slippery coating, deep, slow, thready and hesitant pulse.

[0121] Physical examination: T 36.0 ℃, BP 158 / 96 mmHg; height 156 cm, weight 52 kg; tenderness upon compression of the chest and pelvis (+), hyperreflexia of both knees, Chvostek's sign (±); mild pitting edema of both lower extremities.

[0122] Auxiliary examinations: Scr 468 μmol / L, eGFR 12 mL·min -1 1.73 m -2 BUN 24.7 mmol / L, Ca 1.92 mmol / L, P 2.35 mmol / L↑, ALP 286 U / L↑, PTH 756 pg / mL; 25-(OH)D3 12 ng / mL; lumbar spine + pelvis DR: osteoporosis, mild pelvic deformity.

[0123] Traditional Chinese medicine diagnosis: Spleen and kidney yang deficiency, depletion of essence and blood, malnourishment of bones, and internal stirring of wind.

[0124] The medication described in Example 1 is administered once daily, divided into three oral doses (morning, noon, and evening), 100ml each time, taken warm after meals. During medication, spicy and cold foods should be avoided, and a low-phosphorus, high-quality, low-protein diet (protein 0.6 g / kg) should be followed. -1 ·d -1Phosphorus intake should be limited to <800mg / day; avoid wind and cold, abstain from sexual activity, rest in bed appropriately, and get 30 minutes of gentle sun exposure daily.

[0125] Continue taking sevelamer, calcium carbonate, and calcitriol orally at the same dosage.

[0126] Treatment results: After 3 months of medication, the patient's bone pain was significantly reduced, convulsions disappeared, and the patient could walk independently for 100 meters; aversion to cold and fatigue improved, nocturia decreased to 1-2 times, and stools became formed. Follow-up examination: Ca 2.18 mmol / L, P 1.86 mmol / L, PTH 512 pg / mL; ALP 218 U / L. Traditional Chinese Medicine diagnosis: Complexion improved, aversion to cold decreased, tongue pale red with a thin white coating, pulse deep and stronger than before.

[0127] (2) Li, a 68-year-old male, was admitted to the hospital on November 5, 2024.

[0128] Chief complaint: Maintenance hemodialysis for 5+ years, recurrent muscle aches throughout the body for 1 year.

[0129] Medical History Summary: The patient was diagnosed with stage 5 chronic renal disease (CKD) more than 5 years ago and has been undergoing long-term dialysis treatment. He sought medical attention at a local hospital and was diagnosed with "1. Stage 5 chronic renal disease (CKD) 1) Hypertensive nephropathy 2) Hyperuricemia 3) Renal osteodystrophy; 2. Hemodialysis status." For the past year, he has experienced recurrent generalized muscle aches, cold intolerance, fatigue, abdominal distension, poor appetite, loose stools, and anuria.

[0130] Past medical history: 12 years of hypertension and 8 years of gout.

[0131] Traditional Chinese Medicine Four Diagnostic Methods: Pale and puffy complexion, listless spirit, aversion to cold and cold limbs, soreness and coldness in the lower back and knees, poor appetite and abdominal distension, loose stools and no urination; pale and swollen tongue with teeth marks on the edges, white and slippery coating, and deep, slow and weak pulse.

[0132] Physical examination: T 36.1 ℃, P 58 bpm, R 18 bpm, BP 152 / 94 mmHg; pitting edema of face and lower extremities (++), shifting dullness in abdomen (–), and tenderness in renal area (–).

[0133] Auxiliary examinations: Upon admission, Scr was 412 μmol / L, and eGFR was 21 mL·min. -1 1.73 m -2 , BUN 18.6mmol / L, UA 512 μmol / L; Hb 96 g / L; Ca 2+ 1.80 mmol / L, P 2.02 mmol / L. Renal ultrasound: Both kidneys are reduced in size, with increased cortical echogenicity.

[0134] The medication described in Example 2 is administered once daily, divided into three oral doses of 100ml each, taken warm after meals. During medication, spicy and cold foods should be avoided. Patients are also advised to follow a low-salt (≤3 g / day), low-purine, high-quality, low-protein diet, avoid wind and cold, moderate sexual activity, and get adequate bed rest.

[0135] Treatment efficacy: After two months of continuous medication, the patient's generalized muscle soreness improved, fatigue and cold intolerance lessened, and bowel movements became formed. Follow-up examination showed Scr at 221 μmol / L and eGFR at 29 mL / min. -1 1.73 m -2 , BUN 14.2 mmol / L; Hb 108 g / L, Ca 2+ 2.09 mmol / L, P 1.71 mmol / L. Traditional Chinese Medicine diagnosis: complexion improved to rosy, edema (±), pale red tongue with thin white coating, pulse deep and stronger than before.

Claims

1. A traditional Chinese medicine composition for treating renal osteodystrophy, characterized in that, The traditional Chinese medicine composition consists of the following components in parts by weight: Epimedium 5-30 parts, Astragalus 5-30 parts, Rhubarb 1-12 parts, Atractylodes macrocephala 3-20 parts, and Piper longum 1-15 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition consists of the following components in parts by weight: Epimedium 9-25 parts, Astragalus 9-30 parts, Rhubarb 3-12 parts, Atractylodes macrocephala 6-15 parts, and Piper longum 3-9 parts.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition consists of the following components in parts by weight: Epimedium 10-20 parts, Astragalus 10-20 parts, Rhubarb 3-6 parts, Atractylodes macrocephala 6-15 parts, and Piper longum 3-6 parts.

4. A method for preparing traditional Chinese medicine preparations based on the traditional Chinese medicine composition according to any one of claims 1 to 3, characterized in that, The steps include: S1: Weigh each herb according to the prescription, add 8-20 times the amount of water, soak for 0.5-2 hours; bring to a boil over high heat, then simmer over low heat for 20-60 minutes, filter, and obtain the dregs and liquid. S2: Add 5-20 times the amount of water to the dregs obtained in S1, bring to a boil over high heat, then simmer over low heat for 20-60 minutes. Filter out the decoction and combine it with the decoction obtained in S1 to obtain the Chinese medicine preparation.

5. A traditional Chinese medicine preparation prepared by the method according to claim 4.

6. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3 and / or the traditional Chinese medicine preparation according to claim 5 in the preparation of a medicament for treating renal osteodystrophy.

7. The application according to claim 6, characterized in that, The use of the traditional Chinese medicine composition and / or the traditional Chinese medicine preparation in the preparation of a medicine for treating chronic kidney disease with spleen and kidney yang deficiency.

8. The application according to claim 6, characterized in that, The renal osteodystrophy is characterized by deficiency, cold, blood stasis, and stagnation. The traditional Chinese medicine composition achieves the treatment of renal osteodystrophy through the synergistic effects of warming yang, tonifying qi, resolving blood stasis, and clearing the bowels.

9. The application according to claim 6, characterized in that, The use of the traditional Chinese medicine composition and / or the traditional Chinese medicine preparation in the preparation of a drug having any one or more of the following effects (1)-6): 1) Reduce serum creatinine, blood urea nitrogen, and / or cystatin C levels; 2) Improve renal pathological damage, including reducing renal inflammatory infiltration, interstitial fibrosis and / or tissue calcification; 3) Increase blood calcium levels and / or decrease blood phosphorus levels; 4) Increase bone metabolism levels, including increasing 1,25(OH)2D3 and / or OC levels; 5) Improve bone pathological damage, including reducing bone marrow cavity fat cells, reducing trabecular bone fractures and / or increasing bone mineralization; 6) Improve bone ultrastructural damage, including increasing bone mineral density, percentage bone mass, bone surface density, number of trabeculae, trabecular bone thickness and / or cortical bone thickness of the femur, and reducing trabecular separation.

10. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3 in combination with Western medicine in the preparation of a medicament for treating renal osteodystrophy characterized by deficiency, cold, blood stasis, and stagnation, characterized in that... The aforementioned Western medicines include any one or more of the following: calcium-containing phosphate binders, calcium-free phosphate binders, active vitamin D3, and calcimenizers.

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