A traditional Chinese medicine composition for preventing or / and treating heart-kidney syndrome type 2 and application thereof

Abstract

This invention discloses a traditional Chinese medicine composition for the prevention and / or treatment of type 2 cardiorenal syndrome and its application. By weight, the raw materials of the traditional Chinese medicine composition include: Astragalus membranaceus 15-30 parts, Paeonia lactiflora 10-20 parts, Saposhnikovia divaricata 5-10 parts, Leonurus japonicus 9-30 parts, Massa fermentata 9-30 parts, Poria cocos 10-30 parts, Cinnamomum cassia twig 9-30 parts, Atractylodes macrocephala 10-30 parts, and Glycyrrhiza uralensis 2-10 parts. This traditional Chinese medicine composition is mainly targeted at patients with early-stage renal damage in type 2 cardiorenal syndrome due to spleen-yang deficiency and blood stasis obstructing the collaterals. It utilizes a combination of various traditional Chinese medicines, whose active ingredients synergistically enhance each other, thereby achieving the therapeutic effect of improving early-stage renal damage after chronic heart failure and delaying the pathological progression of type 2 cardiorenal syndrome.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine. More specifically, it relates to a traditional Chinese medicine composition for the prevention and / or treatment of type 2 cardiorenal syndrome and its application. Background Technology

[0002] Cardiorenal syndrome (CRS) refers to an acute or chronic dysfunction of either the heart or kidney that leads to an acute or chronic dysfunction of the other organ. In 2008, Ronco stated that type 2 CRS is chronic renal insufficiency resulting from chronic heart failure (CHF). Renal insufficiency is a common complication of CHF and an independent risk factor associated with poor prognosis in patients with cardiovascular disease.

[0003] In 2019, the ACC / AHA stated that the pathogenesis of CRS remains unclear, and there is no definitive treatment; the disease remains a clinical challenge. Western medicine treatment primarily involves hemodynamic adjustments, treatment of fluid overload, renal replacement therapy (RRT), the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs). CRS can be categorized in Traditional Chinese Medicine (TCM) as "edema," "asthma," "palpitation," "urinary retention," and "phlegm retention." The disease is located in the heart and kidneys, involving dysfunction of the spleen and lungs. TCM syndromes exhibit a certain regular evolution, starting with initial deficiency of heart qi and yin, accompanied by blood stasis and phlegm, gradually progressing from yin deficiency to yang deficiency, from the heart to the kidneys, leading to symptoms such as heart and kidney yang deficiency and water retention. Therefore, clinically, based on different symptom presentations, methods such as tonifying qi, nourishing yin, warming yang, resolving phlegm, promoting blood circulation, and promoting diuresis are often used for syndrome differentiation and treatment.

[0004] Traditional Chinese medicine (TCM) defines CRS based on symptoms such as chest tightness, palpitations, limb edema, shortness of breath, and cough, categorizing them under "phlegm retention," "palpitations," "asthma," "pulmonary distension," and "edema." Its basic pathogenesis is characterized by deficiency of the root and excess of the branch. Some scholars, drawing on the diagnostic and treatment principles of water retention diseases in the *Synopsis of Prescriptions of the Golden Chamber*, believe that the main pathogenesis of CRS is insufficient Yang Qi, impaired fluid distribution, fluid accumulation, and Yang deficiency leading to water retention, resulting in organ dysfunction and functional decline. Furthermore, previous research by our team has confirmed that Yang deficiency is the core pathogenesis of CRS, closely related to the heart, spleen, and kidneys. The heart resides in the upper Jiao, the kidneys in the lower Jiao, and the spleen in the middle Jiao; in the pathogenesis of the heart and kidneys, the spleen plays a central role. In their initial follow-up study of 546 HF patients, the team discovered that the pathogenesis of HF involves a deficiency of heart yang, which, over time, affects the spleen and kidneys, leading to yang deficiency, impaired metabolism of food and fluids, and ultimately, kidney yang deficiency, resulting in chronic kidney disease (CRS). The kidneys are considered the foundation of innate constitution, while the spleen is the foundation of acquired constitution. Traditional Chinese medicine believes that "innate constitution generates acquired constitution, and acquired constitution nourishes innate constitution." In acute / chronic kidney disease, kidney yang deficiency leads to insufficient innate constitution, hindering the development of acquired constitution and causing spleen yang deficiency. Since the spleen governs metabolism, spleen deficiency disrupts this process, leading to abnormal fluid metabolism. Over time, dampness accumulates, suppressing heart yang and resulting in heart yang deficiency and CRS. Therefore, focusing on spleen yang deficiency and developing effective drugs for early-stage CRS is crucial for preventing or delaying its onset. Summary of the Invention

[0005] To address the shortcomings of existing technologies, one objective of this invention is to provide a traditional Chinese medicine composition for the prevention and / or treatment of type 2 cardiorenal syndrome. This composition is primarily targeted at patients with early-stage renal damage in type 2 cardiorenal syndrome due to spleen yang deficiency and blood stasis obstructing the collaterals. It employs a combination of various traditional Chinese medicines, whose active ingredients synergistically enhance each other, thereby achieving the therapeutic effect of improving early-stage renal damage after CHF and delaying the pathological progression of type 2 CRS.

[0006] A second objective of this invention is to provide a traditional Chinese medicine preparation made using the above-mentioned traditional Chinese medicine composition.

[0007] A third objective of this invention is to provide the application of the above-mentioned traditional Chinese medicine composition and preparation.

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

[0009] In a first aspect, the present invention provides a traditional Chinese medicine composition for the prevention and / or treatment of type 2 cardiorenal syndrome. The raw materials of the traditional Chinese medicine composition, by weight, include: 15-30 parts of Astragalus membranaceus, 10-20 parts of Paeonia lactiflora, 5-10 parts of Saposhnikovia divaricata, 9-30 parts of Leonurus japonicus, 9-30 parts of Massa fermentata, 10-30 parts of Poria cocos, 9-30 parts of Cinnamomum cassia, 10-30 parts of Atractylodes macrocephala, and 2-10 parts of Glycyrrhiza uralensis.

[0010] In this invention, Astragalus membranaceus is sweet and warm, and its function is to replenish and promote the flow of Qi. It can greatly replenish the Qi of the heart and spleen. When the Qi is strong, the blood flows smoothly and the blood vessels are not congested. It can also regulate the Qi mechanism, so that the clear Qi rises and the turbid Qi descends. Therefore, it is the principal herb.

[0011] Red peony enters the blood, breaks up blood stasis, and invigorates blood circulation. It assists astragalus in invigorating blood circulation and unblocking collaterals. Moreover, its cool and moist nature prevents the dryness and heat of warming and tonifying drugs from damaging yin. Saposhnikovia divaricata is pungent and warm, promotes yang, dries the spleen and removes dampness, and guides all the drugs to circulate smoothly throughout the body's qi and blood. Motherwort promotes blood circulation, removes blood stasis, eliminates dampness and turbidity, and is especially good at removing the disease of blood stasis and obstruction of collaterals. The three are used as assistant drugs.

[0012] Poria cocos is sweet, bland, and warm in nature. It strengthens the spleen and promotes the transformation of dampness. Cinnamon twig is pungent and sweet, transforming into yang, warming the spleen and assisting its function. This allows the spleen yang to recover, providing a source for the generation of qi and blood, and assisting Poria cocos in strengthening the spleen, replenishing qi, and warming yang. Atractylodes macrocephala is sweet and warm, which can replenish qi, strengthen the spleen, and dry dampness. Massa fermentata strengthens the spleen and promotes its function, and can also break up masses and dissipate blood stasis. The combination of these herbs enhances the efficacy of the principal and assistant herbs, serving as adjuvant herbs.

[0013] Licorice root strengthens the spleen and replenishes qi, and harmonizes the effects of other herbs, serving as a guiding herb.

[0014] The combination of these herbs is warming without being drying, and nourishing without causing stagnation, working together to warm the spleen yang, tonify the spleen qi, disperse blood stasis, and unblock blood vessels.

[0015] Furthermore, according to a specific embodiment of the present invention, the raw materials of the traditional Chinese medicine composition, by weight, include: 20-30 parts of Astragalus membranaceus, 10-15 parts of Paeonia lactiflora, 8-10 parts of Saposhnikovia divaricata, 9-20 parts of Leonurus japonicus, 9-20 parts of Massa fermentata, 15-30 parts of Poria cocos, 9-20 parts of Cinnamomum cassia, 10-20 parts of Atractylodes macrocephala, and 5-10 parts of Glycyrrhiza uralensis.

[0016] According to a specific embodiment of the present invention, the raw materials of the traditional Chinese medicine composition, by weight, include: 30 parts of Astragalus membranaceus, 15 parts of Paeonia lactiflora, 10 parts of Saposhnikovia divaricata, 15 parts of Leonurus japonicus, 15 parts of Massa fermentata, 30 parts of Poria cocos, 12 parts of Cinnamomum cassia, 15 parts of Atractylodes macrocephala, and 10 parts of Glycyrrhiza uralensis.

[0017] According to a specific embodiment of the present invention, the raw materials of the traditional Chinese medicine composition, by weight, include: 30 parts of Astragalus membranaceus, 15 parts of Paeonia lactiflora, 6 parts of Saposhnikovia divaricata, 15 parts of Leonurus japonicus, 15 parts of Massa fermentata, 15 parts of Poria cocos, 10 parts of Cinnamomum cassia, 18 parts of Atractylodes macrocephala, and 10 parts of Glycyrrhiza uralensis.

[0018] According to a specific embodiment of the present invention, the raw materials of the traditional Chinese medicine composition, by weight, include: 30 parts of Astragalus membranaceus, 15 parts of Paeonia lactiflora, 10 parts of Saposhnikovia divaricata, 15 parts of Leonurus japonicus, 15 parts of Massa fermentata, 20 parts of Poria cocos, 10 parts of Cinnamomum cassia, 12 parts of Atractylodes macrocephala, and 10 parts of Glycyrrhiza uralensis.

[0019] According to a specific embodiment of the present invention, the raw materials of the traditional Chinese medicine composition, by weight, include: 20 parts of Astragalus membranaceus, 15 parts of Paeonia lactiflora, 10 parts of Saposhnikovia divaricata, 15 parts of Leonurus japonicus, 15 parts of Massa fermentata, 20 parts of Poria cocos, 12 parts of Cinnamomum cassia, 12 parts of Atractylodes macrocephala, and 10 parts of Glycyrrhiza uralensis.

[0020] According to a specific embodiment of the present invention, preferably, the Atractylodes macrocephala is stir-fried Atractylodes macrocephala, the Medicated Leaven is stir-fried Medicated Leaven, and the Licorice is prepared Licorice.

[0021] The basic formula of the above-mentioned traditional Chinese medicine composition of the present invention can be adjusted according to clinical symptoms during specific implementation to improve certain concurrent clinical symptoms in patients with type 2 cardiorenal syndrome, further enhancing the adaptability of the composition of the present invention and improving the therapeutic effect. These adjustments made based on the basic formula of the present invention are also within the scope of protection of this application.

[0022] Secondly, this invention provides a traditional Chinese medicine preparation for the prevention and / or treatment of type 2 cardiorenal syndrome, which is made from the aforementioned traditional Chinese medicine composition as raw material. The traditional Chinese medicine composition of this invention can be prepared first according to conventional preparation methods in the art, such as decoction, maceration, reflux, etc., and then formulated into various traditional Chinese medicine dosage forms. Optionally, pharmaceutically acceptable excipients can be added during preparation according to the actual needs of formulation shaping.

[0023] The dosage forms of the traditional Chinese medicine preparations include decoctions, tablets, granules, pills, powders, capsules, or powders.

[0024] Thirdly, the present invention provides the use of the above-mentioned traditional Chinese medicine composition or preparation in the preparation of a medicament for the prevention and / or treatment of type 2 cardiorenal syndrome.

[0025] According to specific embodiments of the present invention, the present invention is mainly aimed at the treatment of patients with type 2 cardiorenal syndrome who have chronic heart failure complicated with early renal damage due to spleen yang deficiency and blood stasis obstructing the collaterals.

[0026] In addition, unless otherwise specified, all raw materials of the traditional Chinese medicine composition of the present invention can be obtained commercially available. Any traditional Chinese medicine composition of any range described in the present invention, including the end value and any value between the end values ​​and any sub-range formed by the end value or any value between the end values, can achieve the purpose of preventing and / or treating type 2 cardiorenal syndrome.

[0027] The beneficial effects of this invention are as follows:

[0028] The traditional Chinese medicine composition of this invention has been verified through clinical trials to not only improve cardiac function and TCM syndrome in patients with chronic heart failure, but also protect against early glomerular and tubular damage after chronic heart failure, thus advancing the treatment point for chronic heart failure complicated with kidney damage and helping to delay or block the progression of cardiorenal syndrome. Attached Figure Description

[0029] Figure 1 The cardiac ultrasound images of rats in each group are shown.

[0030] Figure 2 The HE staining results of rats in each group are shown. Detailed Implementation

[0031] To more clearly illustrate the present invention, the following description, in conjunction with preferred embodiments and statistical data, further clarifies the invention. Those skilled in the art should understand that the specific description below is illustrative rather than restrictive and should not be construed as limiting the scope of protection of the present invention.

[0032] Example 1

[0033] The raw materials of the traditional Chinese medicine composition for the prevention and / or treatment of type 2 cardiorenal syndrome are: Astragalus membranaceus 30g, Paeonia lactiflora 15g, Saposhnikovia divaricata 6g, Leonurus japonicus 15g, stir-fried Shenqu 15g, Poria cocos 15g, Cinnamomum cassia 10g, stir-fried Atractylodes macrocephala 18g, and prepared Glycyrrhiza uralensis 10g.

[0034] Example 2

[0035] The raw materials for the drug for the prevention and / or treatment of type 2 cardiorenal syndrome are: Astragalus membranaceus 30g, Paeonia lactiflora 15g, Saposhnikovia divaricata 10g, Leonurus japonicus 15g, stir-fried Shenqu 15g, Poria cocos 20g, Cinnamomum cassia 10g, stir-fried Atractylodes macrocephala 12g, and prepared Glycyrrhiza uralensis 10g.

[0036] The above-mentioned raw materials are boiled in water to make a decoction.

[0037] Example 3

[0038] The raw materials for the drug for the prevention and / or treatment of type 2 cardiorenal syndrome are: Astragalus membranaceus 30g, Paeonia lactiflora 15g, Saposhnikovia divaricata 10g, Leonurus japonicus 15g, stir-fried Shenqu 15g, Poria cocos 30g, Cinnamomum cassia 12g, stir-fried Atractylodes macrocephala 15g, and prepared Glycyrrhiza uralensis 10g.

[0039] The above-mentioned active pharmaceutical ingredient was prepared into granules according to the granule preparation method in this field.

[0040] Clinical Study of Case 1

[0041] The clinical efficacy and safety of the granules (Wenpi Tongluo Granules) prepared in Example 3 of this invention in the treatment of type 2 cardiorenal syndrome were observed.

[0042] Patients who visited the Department of General Medicine at Guang'anmen Hospital between January 2021 and January 2023 were included in this study and received continuous treatment for 4 weeks. Renal function tests were performed after 4 weeks. Renal function improved in 35 patients, with a total effective rate of 89.7%. The urinary N-acetyl-β-D-glucosidase (NAG) enzyme, a renal tubular injury marker, significantly improved after treatment, and the difference between the two groups was statistically significant (P < 0.05), indicating that this preparation can effectively improve renal tubular function in patients with cardiorenal syndrome.

[0043] Table 1. Effectiveness of Wenpi Tongluo Granules in the Treatment of CRS

[0044] Number of examples (items) Invalid (number) Effective (number) Overall effectiveness (%) Wenpi Tonglu Granules 39 4 35 89.7

[0045] Table 2. Indicators related to the improvement of proteinuria in CRS patients by Wenpi Tongluo Granules

[0046]

[0047] Experimental Example 2

[0048] Effects of the herbal composition of this invention on cardiac and renal function in rats with type 2 cardiorenal syndrome

[0049] 1. Materials

[0050] 1.1 Laboratory Animals

[0051] Healthy SPF-grade male SD rats aged 8 weeks were purchased from Beijing Vital River Laboratory Animal Co., Ltd.

[0052] 1.2 Experimental reagents

[0053] The prescription of the traditional Chinese medicine composition of this invention is as follows: Astragalus membranaceus 30g, Paeonia lactiflora 15g, Saposhnikovia divaricata 10g, Leonurus japonicus 15g, stir-fried Shenqu 15g, Poria cocos 30g, Cinnamomum cassia 12g, stir-fried Atractylodes macrocephala 15g, and prepared Glycyrrhiza uralensis 10g.

[0054] 1.3 Experimental Apparatus

[0055] TA 1003 Precision Electronic Balance (Shanghai Balance Instrument Factory, China)

[0056] HP5500 Color Doppler Ultrasonic Imaging System (Philips, USA)

[0057] HX-300S Animal Ventilator (Chengdu Taimeng Technology Co., Ltd., China)

[0058] Low-temperature, high-capacity centrifuge (Jouan, France)

[0059] SIM-F140AY65 Ice Maker (Sanyo Corporation, Japan)

[0060] -80°C ultra-low temperature freezer (Thermo Fisher Scientific, USA)

[0061] MILLI-Qicidemic ultrapure water system (Millipore, France)

[0062] Encapsulation machine (Wuhan Junjie Electronics Co., Ltd., China)

[0063] Dehydrator (Wuhan Junjie Electronics Co., Ltd., China)

[0064] Pathology microtome (Leica, Germany)

[0065] Slice baking machine (Changzhou Guohua Electric Appliance Co., Ltd., China).

[0066] 2 Methods

[0067] 2.1 Animal Model

[0068] Experimental model establishment method: Intraperitoneal injection of lily alkaloid (MCT): After 1 week of acclimatization feeding, lily alkaloid (MCT) 30 mg / kg / d was injected intraperitoneally. 4 weeks after injection, CRS rats showed a 3-fold increase in serum brain natriuretic peptide (BNP) and a 2-fold increase in NGAL compared to the sham-operated group. The kidney tissue showed pathological signs of renal tubular swelling and cell death, which indicated successful model establishment.

[0069] 2.2 Animal grouping

[0070] The subjects were divided into a healthy group, a model group, and a traditional Chinese medicine group. The healthy group and the model group were administered an equal volume of distilled water by gavage, while the traditional Chinese medicine group (15.96 g / kg / d) was dissolved in an equal volume of distilled water and administered by gavage.

[0071] 2.3 Drug intervention methods

[0072] 2.3.1 Drug preparation method

[0073] Preparation method of traditional Chinese medicine: Decoction twice according to conventional decoction method, mix the two filtrates, filter the resulting liquid through double-layer gauze, and evaporate by water bath heating to obtain a concentrated solution with a concentration of 6g / ml. Store in a refrigerator at 4℃ for later use. Dilute with distilled water according to the ratio before each use.

[0074] 2.3.2 Administration method

[0075] One week after model establishment, medication was initiated. The healthy group and the model group received an equal volume of distilled water. The daily clinical dosage for the traditional Chinese medicine group was: Astragalus membranaceus 30g, Paeonia lactiflora 15g, Saposhnikovia divaricata 10g, Leonurus japonicus 15g, stir-fried Shenqu (medicated leaven) 15g, Poria cocos 30g, Cinnamomum cassia 12g, stir-fried Atractylodes macrocephala 15g, and prepared Glycyrrhiza uralensis 10g. Based on the human and rat body surface area conversion method, with a human weight of 60kg, the equivalent dose for rats is approximately 6.3 times that of humans, i.e., 15.96g / kg.

[0076] 2.3.3 Collection of materials

[0077] Four weeks after gavage, echocardiography was performed again, and 24-hour urine and fecal samples were collected and weighed. Rats were sedated by intraperitoneal injection of 5% chloral hydrate (300 mg / kg). Blood samples were collected from the rats using the abdominal aorta method and placed in separate vacuum blood collection tubes (3.5 ml) and anticoagulant violet tubes (3.5 ml). After standing for 2 hours, the samples were centrifuged (4℃, 3000 r / min, 10 min), and the supernatant was stored at -80℃. Following the abdominal aorta blood collection, the heart, kidneys, and other tissues were removed sequentially via abdominal and thoracotomy. The kidney capsule and adipose tissue were trimmed and removed, and the surface moisture of the kidneys was absorbed with gauze. The left and right atrial appendages were trimmed, and sterile gauze was soaked in physiological saline to absorb blood stains. The heart and kidneys were weighed separately, and the corresponding tissues were preserved in the appropriate fixatives according to the light or electron microscopy requirements. Tissues for Western blotting / PCR were frozen in cryovials at -80℃.

[0078] 2.4 Observation Indicators and Methods

[0079] 2.4.1 General Case

[0080] During routine gavage, record the animal's condition in detail, observe its basic characteristics and its feeding, watering, and excretion, and weigh it at a fixed time each week.

[0081] 2.4.2 Urine protein test

[0082] The levels of NT-proBNP, NAG, KIM, and NGAL were detected using enzyme-linked immunosorbent assay (ELISA).

[0083] 2.4.3 Echocardiography

[0084] The HP5500 color Doppler ultrasound imaging system was used for the detection.

[0085] 2.4.4 HE staining of kidney tissue

[0086] HE staining method: (1) Fixation: Place the tissue specimen in 4% paraformaldehyde for 48 hours, with the solution volume being more than 10 times that of the specimen; (2) Trimming: Trim the fixed tissue into thin slices of about 3 mm. Different tissues have different optimal cutting surfaces. Place the cut specimens in an embedding cassette and mark them with a pencil; (3) Rinsing: Rinse with running water for 30 minutes. Connect a soft tube and let the water flow from bottom to top to better remove formaldehyde from the tissue; (4) Dehydration and paraffin infiltration: After rinsing, proceed to the next step of dehydration and paraffin infiltration. Generally, automatic machines require 10 hours. Choose to run it at night. After completion, remove the tissue and wrap it. (5) Embedding: Embed the tissue using a metal mold, then place it on a cooling table for solidification until the tissue block can be gently broken off. Clean the remaining wax on both sides of the tissue block neatly. (6) Sectioning: When slicing, first coarsely cut and then finely cut. When finely cutting, adjust the thickness to 2um and the speed to 20. The water temperature for spreading the slide is 42℃ (45℃). After spreading the slide, use a glass slide to pick up the slide. Insert the glass slide roughly vertically into the water, slightly touch the tissue, and then lift it up. Pick up the tissue slide directly, mark it with a pencil, and place it in a slicing tray. (7) Drying: After all the sections are cut, place the sections in a 37℃ oven for 3 hours. Do not leave them overnight. (8) Dehydration: After drying the sections, place them in xylene I for 20 min, xylene II for 20 min, and then wash with a gradient of ethanol (100% → 95% → 90% → 80% → 70%). Finally, rinse with distilled water. (9) Hematoxylin staining: Place the sections in hematoxylin solution for 8 min, rinse with tap water, differentiate with 1% hydrochloric acid alcohol, rinse with tap water again, place in 0.6% ammonia water to return to blue, and finally rinse with tap water. (10) Eosin staining: Stain with 1% eosin water for 10 min, and rinse with tap water for 2 min. (11) Dehydration and mounting: 70% → 80% → 90% → 95% ethanol for 2 min each, anhydrous ethanol I and II for 2 min each, xylene I and II for 2 min each, and finally mount with neutral resin. Observe and photograph the sections under a microscope.

[0087] 3 Results

[0088] 3.1 General Situation

[0089] During the experiment, the healthy rats were in good health; the model rats were lethargic, had dull fur, reduced activity, sluggish reactions, and increased urine output; the rats in the traditional Chinese medicine group showed significantly improved mental state and reactions compared to the model group, and reduced urine output.

[0090] 3.2 Changes in echocardiography

[0091] Figure 1 Echocardiogram images of rats in each group. Figure 1The results show that the traditional Chinese medicine group improved cardiac function. Furthermore, as shown in Table 3 below: compared with the healthy group, the model group showed significantly lower LVEF and FS (P<0.05), while LVIDS, LVIDD, HR, and CO showed no significant changes (P>0.05); compared with the model group, the traditional Chinese medicine group showed significantly higher LVEF (P<0.05), while the other groups showed no significant changes.

[0092] Table 3 Results of echocardiography

[0093]

[0094] △ P<0.05, P<0.01 compared with the healthy group; ▲ P<0.05, compared with the model group

[0095] 3.3 Changes in NT-proBNP, NAG, KIM, and NGAL

[0096] As shown in Table 4 below: Compared with the healthy group, the model group showed significantly elevated levels of NT-proBNP, NAG, and KIM (P<0.05), while NGAL showed a slightly elevated level (P>0.05). Compared with the model group, the traditional Chinese medicine group showed significantly lower levels of NT-proBNP and NAG (P<0.05), while KIM and NGAL showed no significant changes.

[0097] Table 4. Results of serum creatinine, blood urea nitrogen, and brain natriuretic peptide tests

[0098]

[0099] △ P<0.05, P<0.01 compared with the healthy group; ▲ P<0.05, compared with the model group

[0100] 3.4 Renal pathological changes in type 2 CRS rats

[0101] Animal experiments revealed that in the healthy group, glomeruli were normal in morphology and size, with visible brush borders and clear cortical-medullary boundaries; renal tubules were neatly arranged with clear structure, and no significant changes were observed in epithelial cells; renal vessels and interstitium showed no obvious abnormalities. In the model group, granular or vacuolar changes were observed in renal tubular epithelial cells, with cell flattening, lumen dilation, brush border detachment, and hyaline, granular, or cellular casts visible within the lumen. Epithelial cell apoptosis, inflammatory cell infiltration, and glomerular capillary destruction were also observed. The intervention with traditional Chinese medicine improved renal tubular epithelial cell death, inflammatory cell infiltration, lumen dilation, and hyaline changes, and effectively reduced glomerular damage. Figure 2 As shown.

[0102] Trial Case 3: Typical Cases and Treatment Efficacy

[0103] The following selected typical clinical cases demonstrate the specific application of the technical solution of this invention. In practical applications, many more cases can prove that the prescriptions and dosages covered by the technical solution of this invention can achieve similar effects.

[0104] Case 1: Patient Mao, male, 83 years old, first visit date: September 30, 2021.

[0105] Chief complaint: Intermittent chest tightness and shortness of breath for 6 years.

[0106] Current symptoms: Chest tightness and shortness of breath after mild activity, decreased walking ability, fatigue after about 50 meters, accompanied by dizziness, fluctuating self-measured blood pressure, no obvious aversion to cold, occasional cold hands and feet, no obvious increase in sweating, poor appetite, abdominal distension after meals, normal sleep, no snoring, daytime drowsiness that occurs as blood pressure decreases, mild edema in both lower limbs, scanty urine, constipation, dark red tongue with thin white coating, and deep and slippery pulse. N-terminal pro-B-type natriuretic peptide (NT-proBNP) assay: 306.5; Urine protein analysis: urinary NAG enzyme (NAG) 19.20 U / L, urinary microalbumin (MA) 66.5 mg / L, urinary microalbumin / creatinine (MA / CR) 40.93 mg / g, CR, urinary retinol-binding protein (URBP) 0.41 mg / L, urinary immunoglobulin G (IGU) 2.11 mg / dL, urinary transferrin (TRU) 0.276 mg / dL, α1 microglobulin (A1M) 4.92 mg / dL.

[0107] Past medical history: 4-year history of hypertension, with a highest blood pressure of 180 / 100 mmHg. Regularly taking amlodipine besylate tablets, blood pressure is reasonably controlled.

[0108] Western medical diagnosis: 1. Heart failure, grade III; 2. Renal insufficiency; 3. Hypertension.

[0109] Traditional Chinese Medicine Diagnosis: Asthma due to spleen yang deficiency and blood stasis obstructing the collaterals

[0110] Treatment: Warm the spleen and unblock the meridians.

[0111] prescription:

[0112] Raw Astragalus 30g, Red Peony Root 15g, Saposhnikovia Root 6g, Motherwort 15g, Fried Medicated Leaven 15g, Prepared Licorice Root 10g, Poria 15g, Cinnamon Twig 10g, Atractylodes Rhizome 18g, Ginger-processed Magnolia Bark 10g, Ligusticum Rhizome 15g, Vinegar-processed Cyperus Rhizome 10g, Wine-processed Cistanche 15g, Cannabis Seed 15g, Codonopsis Root 15g. Fourteen doses, decocted in water, one dose per day, divided into morning and evening doses. Continue Western medicine, maintain a light diet, and engage in moderate physical activity. Note: The patient experienced abdominal distension after meals; therefore, Ligusticum Rhizome, Magnolia Bark, and Cyperus Rhizome were added to the basic formula to promote qi circulation and relieve distension. The patient also suffered from constipation; therefore, Wine-processed Cistanche and Cannabis Seed were added to moisten the intestines and promote bowel movements.

[0113] Second visit: The patient reported that shortness of breath was relieved after activity, but chest tightness occurred after changing posture. Blood pressure was well controlled. Appetite was poor, with no abdominal distension after meals. Mild edema persisted in both lower limbs. Urination was normal, but bowel movements were infrequent. The tongue was dark red with a thin, dry, yellow coating, and the pulse was slippery. Prescription: Add 12g of Polyporus umbellatus, 15g of Alisma plantago-aquatica, 10g of Scutellaria baicalensis, and 10g of Cornus officinalis to the above prescription. Fourteen doses, decocted in water, one dose per day, taken warm in the morning and evening. Note: Polyporus umbellatus and Alisma plantago-aquatica were added to the previous prescription to promote diuresis, eliminate dampness, and reduce swelling; Scutellaria baicalensis clears heat and purges fire; and Codonopsis pilosula strengthens the spleen and replenishes qi.

[0114] Third visit: The patient reported significant relief of chest tightness and shortness of breath after activity, and was able to walk half a bus stop's distance. Appetite was good, with no hiccups, abdominal distension, sweating, or chills. There was no edema in the lower extremities. Urination was normal, but bowel movements were infrequent. The tongue was dark red with a white, greasy coating, and the pulse was wiry and slippery. Urine protein analysis showed: NAG enzyme (NAG) 7.49 U / L, microalbumin (MA) 15.2 mg / L, microalbumin / creatinine (MA / CR) 30.13 mg / g, CR, retinol-binding protein (URBP) 0.19 mg / L, immunoglobulin G (IGU) 0.406 mg / dL, transferrin (TRU) <0.2 mg / dL, and α1-microglobulin (A1M) 1.28 mg / dL. Prescription: The previous prescription was modified by removing Polyporus umbellatus and Cornus officinalis, and adding 9g of stir-fried bitter almond. Note: Since the patient's edema disappeared and the stool was loose, Polyporus umbellatus was removed and bitter almond was added to moisten the intestines and promote bowel movement.

[0115] Case 2: Patient Hao, female, 87 years old, first visit date: September 7, 2021.

[0116] Chief complaint: Intermittent chest tightness and shortness of breath for 3 months.

[0117] Current symptoms: Shortness of breath, worsening with activity and relieved by rest; accompanied by cough and sputum, excessive sweating, fatigue, no aversion to cold, poor appetite, occasional abdominal distension, nausea and vomiting, cold extremities, poor sleep, scanty urination, normal bowel movements. The tongue is dark red with a white coating, and the pulse is slippery and irregular. Urine protein analysis: NAG enzyme (NAG) 20.7 U / L, microalbumin (MA) 170.9 mg / L, microalbumin / creatinine (MA / CR) 311.51 mg / g, CR, retinol-binding protein (URBP) 0.47 mg / L, immunoglobulin G (IGU) 1.68 mg / dL, transferrin (TRU) 0.425 mg / dL, α1-microglobulin (A1M) 2.32 mg / dL.

[0118] Past medical history: hypertension, type 2 diabetes

[0119] Western medical diagnosis: 1. Chronic heart failure, NYHA class II; 2. Renal tubular disease; 3. Insomnia; 4. Type 2 diabetes mellitus.

[0120] Traditional Chinese Medicine Diagnosis: Asthma due to spleen yang deficiency and blood stasis obstructing the collaterals

[0121] prescription:

[0122] Raw Astragalus 30g, Red Peony Root 15g, Saposhnikovia Root 10g, Motherwort 15g, Fried Medicated Leaven 15g, Prepared Licorice Root 10g, Poria 20g, Cinnamon Twig 10g, Fried Atractylodes Rhizome 12g, Raw Malt 15g, Buddha's Hand 10g, Codonopsis Root 15g, Ophiopogon Root 10g. Fourteen doses, decocted in water, one dose per day, divided into morning and evening doses. Instructed to maintain a light diet and moderate exercise. Note: The patient had poor appetite, so raw malt was added to the basic formula to strengthen the spleen, improve appetite, and aid digestion. For abdominal distension, Buddha's Hand was added to regulate qi and harmonize the stomach. For a feeling of relief, Codonopsis Root was added to strengthen the spleen and replenish qi. For excessive sweating and insomnia, Ophiopogon Root was added to benefit the stomach, generate fluids, clear the heart, moisten the lungs, and resolve phlegm.

[0123] Second visit: The patient reported that shortness of breath and wheezing after activity had improved compared to before, but cough and phlegm persisted. Appetite had improved compared to before, but abdominal distension and hiccups still occurred occasionally after meals. Fatigue remained as before. Bowel movements were normal. Tongue was dark red with a white coating, and pulse was thready and slippery. Prescription: The above prescription was modified by removing Ophiopogon japonicus and adding Platycodon grandiflorus 10g, Aucklandia lappa 6g, stir-fried hawthorn 15g, Amomum villosum 6g, and Pinellia ternata 9g. Fourteen doses, decocted in water and taken once a day, warm in the morning and evening. Note: The patient still had cough and phlegm, so Ophiopogon japonicus was removed from the previous prescription, and Platycodon grandiflorus and Pinellia ternata were added to enhance the effect of clearing the lungs and resolving phlegm; abdominal distension was relieved by adding Aucklandia lappa, Amomum villosum, and stir-fried hawthorn 15g to regulate qi, strengthen the spleen, and promote digestion.

[0124] Third visit: The patient reported that shortness of breath after activity was significantly reduced compared to before, with occasional shortness of breath, no cough or sputum, improved walking ability, good appetite, normal bowel movements, reduced fatigue, cold lower limbs, dark red tongue with thin white coating, and a wiry and slippery pulse. Repeat urine protein analysis: urine NAG enzyme (NAG) 10.14 U / L, urine microalbumin (MA) 159.7 mg / L, urine microalbumin / creatinine (MA / CR) 296.62 mg / g, CR, urine retinol-binding protein (URBP) 0.41 mg / L, urine immunoglobulin G (IGU) 1.50 mg / dL, urine transferrin (TRU) 0.389 mg / dL, α1-microglobulin (A1M) 1.38 mg / dL. Prescription: Remove Pinellia ternata, add 9g of peach kernel and 9g of safflower. Note: After taking the above prescription, the cough and phlegm were relieved, so Pinellia was removed; the patient's lower limbs were cold, which was considered to be caused by poor blood circulation and blood stasis, so Peach kernel and Safflower were added to promote blood circulation, remove blood stasis and unblock the collaterals.

[0125] Case 3: Patient Wang, male, 78 years old, first visit date July 27, 2021.

[0126] Chief complaint: Intermittent chest tightness and shortness of breath for 4 years.

[0127] Current symptoms: Intermittent chest tightness and shortness of breath, significantly aggravated by exertion, no wheezing, occasional chest pain relieved by rest, cough with white, sticky sputum that is difficult to expectorate, occasional palpitations, excessive sweating, mainly in the chest and back, poor appetite, no acid reflux or heartburn, no stomach pain, aversion to cold, mild edema in both lower limbs, sleep is good, bowel movements 1-2 times / day, formed stool, frequent urination, incomplete urination, foamy urine, nocturia 4-5 times. Pale tongue with white, peeled coating, deep and wiry pulse. Urine protein analysis: NAG enzyme (NAG) 30.12 U / L, microalbumin (MA) 28.4 mg / L, microalbumin / creatinine (MA / CR) 14.4 mg / g, CR, retinol-binding protein (URBP) 0.42 mg / L, immunoglobulin G (IGU) 0.819 mg / dL, transferrin (TRU) <0.2 mg / dL, α1-microglobulin (A1M) 2.65 mg / dL.

[0128] Past medical history: 3-year history of hypertension, with a highest blood pressure of 180 / 110 mmHg. Blood pressure is controlled by regularly taking bisoprolol fumarate tablets 5mg once a day, with self-monitored blood pressure fluctuations between 120-140 / 70-80 mmHg; 1-year history of hyperlipidemia, currently taking ezetimibe tablets 10mg once a day + atorvastatin calcium tablets 5mg twice a day to lower lipids.

[0129] Western medical diagnosis: 1. Chronic heart failure, NYHA class II; 2. Renal tubular disease; 3. Hypertension; 4. Hyperlipidemia.

[0130] Traditional Chinese Medicine Diagnosis: Heart-related disease with spleen yang deficiency and blood stasis obstructing the collaterals.

[0131] prescription:

[0132] Raw Astragalus 20g, Red Peony Root 15g, Saposhnikovia Root 10g, Motherwort 15g, Fried Medicated Leaven 15g, Prepared Licorice Root 10g, Poria 20g, Cinnamon Twig 12g, Raw Atractylodes Rhizome 12g, Trichosanthes Fruit 10g, Salvia Root 15g. Twenty-eight doses, decocted in water and taken once daily, divided into morning and evening doses. Instructed to continue taking Western medicine, maintain a light diet, and engage in moderate activity. Note: The patient had a cough and phlegm; Trichosanthes Fruit was added to moisten the lungs and resolve phlegm. Blood stasis in the chest and heart obstructed the flow of qi and blood, causing pain; therefore, Salvia Root was added to invigorate blood, remove blood stasis, and relieve pain.

[0133] Second visit: The patient reported significant improvement in chest tightness and shortness of breath, with no chest pain or palpitations. Cough and phlegm were reduced compared to before. Appetite and sleep were good, bowel movements were regular, and there was no edema in both lower extremities. The tongue was dark red with a broad white coating, and the pulse was wiry. The above prescription was effective; continue taking it for 14 more doses.

[0134] Afterwards, the prescription was slightly adjusted according to the changes in the patient's condition during follow-up visits. After three months of treatment, the patient's chest tightness and shortness of breath basically disappeared, and all other symptoms were relieved compared to before.

[0135] Table 5 Treatment outcomes of three typical cases

[0136]

[0137] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. For those skilled in the art, other variations or modifications can be made based on the above description. It is impossible to exhaustively list all the implementation methods here. All obvious variations or modifications derived from the technical solutions of the present invention are still within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for the prevention and / or treatment of type 2 cardiorenal syndrome, characterized in that, The traditional Chinese medicine composition, by weight, is made from the following raw materials: Astragalus membranaceus 15-30 parts, Paeonia lactiflora 10-20 parts, Saposhnikovia divaricata 5-10 parts, Leonurus japonicus 9-30 parts, Massa fermentata 9-30 parts, Poria cocos 10-30 parts, Cinnamomum cassia twig 9-30 parts, Atractylodes macrocephala 10-30 parts, and Glycyrrhiza uralensis 2-10 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition, by weight, is made from the following raw materials: Astragalus membranaceus 20-30 parts, Paeonia lactiflora 10-15 parts, Saposhnikovia divaricata 8-10 parts, Leonurus japonicus 9-20 parts, Massa fermentata 9-20 parts, Poria cocos 15-30 parts, Cinnamomum cassia twig 9-20 parts, Atractylodes macrocephala 10-20 parts, and Glycyrrhiza uralensis 5-10 parts.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition, by weight, is made from the following raw materials: Astragalus membranaceus 30 parts, Paeonia lactiflora 15 parts, Saposhnikovia divaricata 10 parts, Leonurus japonicus 15 parts, Massa fermentata 15 parts, Poria cocos 30 parts, Cinnamomum cassia 12 parts, Atractylodes macrocephala 15 parts, and Glycyrrhiza uralensis 10 parts.

4. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition, by weight, is made from the following raw materials: Astragalus membranaceus 30 parts, Paeonia lactiflora 15 parts, Saposhnikovia divaricata 6 parts, Leonurus japonicus 15 parts, Massa fermentata 15 parts, Poria cocos 15 parts, Cinnamomum cassia 10 parts, Atractylodes macrocephala 18 parts, and Glycyrrhiza uralensis 10 parts.

5. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition, by weight, is made from the following raw materials: 30 parts Astragalus membranaceus, 15 parts Paeonia lactiflora, 10 parts Saposhnikovia divaricata, 15 parts Leonurus japonicus, 15 parts Massa fermentata, 20 parts Poria cocos, 10 parts Cinnamomum cassia, 12 parts Atractylodes macrocephala, and 10 parts Glycyrrhiza uralensis.

6. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition, by weight, is made from the following raw materials: 20 parts Astragalus membranaceus, 15 parts Paeonia lactiflora, 10 parts Saposhnikovia divaricata, 15 parts Leonurus japonicus, 15 parts Massa fermentata, 20 parts Poria cocos, 12 parts Cinnamomum cassia, 12 parts Atractylodes macrocephala, and 10 parts Glycyrrhiza uralensis.

7. The traditional Chinese medicine composition according to any one of claims 1-6, characterized in that, The Atractylodes macrocephala mentioned is stir-fried Atractylodes macrocephala, the Shenqu mentioned is stir-fried Shenqu, and the licorice mentioned is roasted licorice.

8. A traditional Chinese medicine preparation for the prevention and / or treatment of type 2 cardiorenal syndrome, characterized in that, The traditional Chinese medicine preparation includes the traditional Chinese medicine composition according to any one of claims 1-7.

9. The traditional Chinese medicine preparation according to claim 8, characterized in that, The traditional Chinese medicine preparation also includes pharmaceutically acceptable excipients.

10. The traditional Chinese medicine preparation according to claim 8 or 9, characterized in that, The dosage forms of the traditional Chinese medicine preparations include decoctions, tablets, granules, pills, powders, capsules, or powders.

11. The use of the traditional Chinese medicine composition according to any one of claims 1-7 or the traditional Chinese medicine preparation according to any one of claims 8-10 in the preparation of a medicament for the prevention and / or treatment of type 2 cardiorenal syndrome.

12. The application according to claim 11, characterized in that, The type 2 cardiorenal syndrome is chronic heart failure complicated by early kidney damage due to spleen yang deficiency and blood stasis obstructing the collaterals.

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