Application of traditional Chinese medicine composition in preparation of medicine for preventing and / or treating heart failure

Abstract

The invention provides application of a traditional Chinese medicine composition in preparation of a medicine for preventing and / or treating heart failure. The traditional Chinese medicine composition comprises glechoma longituba, rumex madaio, saxifraga stolonifera, sabia parviflora, phoenix-tail fern, scutellaria baicalensis, golden cypress and andrographis paniculata. The mass ratio of the glechoma longituba to the nepal dock root to the saxifraga stolonifera to the sabia parviflora to the phoenix-tail fern to the scutellaria baicalensis to the golden cypress to the common andrographis herb is (30-54): (39-45): (34-47): (24-67): (26-62): (26-62): (24-67): (30-54). According to the traditional Chinese medicine composition, various traditional Chinese medicine components are matched for use, heart failure can be effectively treated, and the heart function of a patient is improved.

Description

Technical Field

[0001] This invention belongs to the technical field of new product applications, specifically relating to the application of a traditional Chinese medicine composition in the preparation of a drug for the prevention and / or treatment of heart failure. Background Technology

[0002] Heart failure is the end-stage of many cardiovascular diseases, with a persistently high prevalence worldwide, posing a significant public health burden. Diagnosed patients typically require lifelong medication, placing a substantial economic and care burden on them and severely impacting their physical function, mental well-being, and overall quality of life. Currently, standardized management of heart failure in modern medicine primarily relies on drug regimens centered on neuroendocrine inhibitors. Commonly used medications include angiotensin-converting enzyme inhibitors, beta-blockers, and aldosterone receptor antagonists, often combined with diuretics to control fluid retention. While this regimen helps improve cardiac function and slow disease progression in some patients, its long-term use has significant limitations, such as potential adverse reactions like hypotension, electrolyte imbalances, and kidney damage, and in some patients, it may even increase the risk of death. Therefore, safer and more effective treatment options are still needed in clinical practice.

[0003] In Traditional Chinese Medicine (TCM) theory, symptoms of heart failure can be categorized under "palpitation," "dyspnea," and "edema / phlegm retention," which modern TCM refers to as "heart failure." TCM emphasizes a holistic and dynamic understanding of disease. While heart failure manifests as weakness in myocardial contraction (i.e., "heart qi deficiency"), its underlying pathogenesis often involves multiple organs, closely related to the functions of the kidneys and spleen. The core pathogenesis is often a deficiency of heart and kidney yang qi, leading to qi deficiency, blood stasis, and internal retention of fluids, creating a complex situation of deficiency in the root and excess in the branch. Kidney yang is the root of yang qi in the body, warming heart yang and jointly promoting blood circulation. When heart and kidney yang qi are deficient, it leads to "qi deficiency and weakness," reducing the function of propelling blood flow and resulting in a pathological state of "blood stasis." Prolonged blood stasis further affects fluid metabolism, causing "internal retention of fluids," resulting in edema and dyspnea. Especially in elderly patients, due to the weakening of their vital energy and the damage caused by prolonged illness, this pathological process is often more protracted and difficult to cure.

[0004] However, it is worth noting that in long-term clinical practice, existing traditional Chinese medicine interventions, primarily based on the principles of invigorating qi, warming yang, promoting blood circulation, and diuresis, may also face issues such as fluctuating efficacy or individual differences in response. This suggests that the pathological mechanisms of heart failure are complex, and the key aspects of the pathogenesis may differ at different stages and among different patients. A single treatment method or fixed prescription cannot fully cover all clinical needs. Therefore, further exploring traditional Chinese medicine treatment strategies with different characteristics of action, based on existing treatments, still has significant clinical importance and research value. Summary of the Invention

[0005] To address the problems and shortcomings of existing technologies, this invention provides an application of a traditional Chinese medicine composition in the preparation of a drug for the prevention and / or treatment of heart failure. In this application, the traditional Chinese medicine composition, by using a combination of various traditional Chinese medicine ingredients, can effectively treat heart failure and improve the patient's cardiac function.

[0006] According to one aspect of the present invention, a traditional Chinese medicine composition is provided for use in the preparation of a medicament for the prevention and / or treatment of heart failure. The traditional Chinese medicine composition comprises: *Glechoma hederacea*, *Rheum palmatum*, *Saxifraga stolonifera*, *Clematis chinensis*, *Pteris vittata*, *Scutellaria baicalensis*, *Phellodendron chinense*, and *Andrographis paniculata*; calculated by mass ratio, *Glechoma hederacea*: *Rheum palmatum*: *Saxifraga stolonifera*: *Clematis chinensis*: *Pteris vittata*: *Scutellaria baicalensis*: *Phellodendron chinense*: *Andrographis paniculata* = 30~54: 39~45: 34~47: 24~67: 26~62: 26~62: 24~67: 30~54.

[0007] In Traditional Chinese Medicine (TCM) theory, heart failure falls under the categories of "asthma," "heart obstruction," "heart edema," and "heart failure." Its etiology and pathogenesis are complex and varied, often exhibiting a combination of deficiency and excess, clinically revealing deficiencies in the heart, spleen, and kidneys, along with excesses such as water retention and blood stasis. The core pathogenesis lies in heart and kidney yang deficiency and water retention and blood stasis. Treatment focuses on tonifying qi and warming yang, promoting blood circulation and diuresis. Targeting this pathogenesis, the TCM composition provided in this invention uses a combination of herbs including *Glechoma hederacea*, *Rheum palmatum*, *Saxifraga stolonifera*, *Clematis armandii*, *Pteris vittata*, *Scutellaria baicalensis*, *Phellodendron chinense*, and *Andrographis paniculata*, formulated according to specific mass ratios. This composition holistically regulates the key pathological aspects of heart failure, aiming to achieve a balance of qi, blood, yin, and yang, and treat the internal organs simultaneously.

[0008] The various active ingredients in this composition, under specific formulation conditions, work synergistically to invigorate Qi and warm Yang, promote blood circulation and diuresis, thus exhibiting a comprehensive regulatory effect in preventing and improving heart failure. Specifically, this composition helps enhance myocardial contractility, reduce cardiac load, and increase cardiac output, thereby improving cardiac pumping function; it also improves blood rheology, reduces cardiac afterload, increases myocardial oxygen supply, and promotes cardiac function recovery and ventricular structure improvement. Furthermore, this formula also regulates the body's immune function and enhances the patient's own resistance, which is beneficial for improving left ventricular systolic and diastolic function, delaying ventricular remodeling, and positively impacting microcirculation and myocardial ischemia; it can also inhibit the excessive production of endothelin and tumor necrosis factor, assist in vasodilation, slow heart rate, and reduce myocardial oxygen consumption, thereby improving myocardial blood supply and protecting cardiac function.

[0009] Glechoma hederacea is pungent and slightly bitter in nature, cool in taste, and enters the liver, kidney, and bladder meridians. Its pungent and bitter properties help to disperse and drain dampness, and its cool nature allows it to clear heat. Entering the liver, kidney, and bladder meridians, it is an excellent medicine for promoting diuresis and relieving jaundice. It not only promotes diuresis and relieves jaundice, clears heat and detoxifies, making it an essential medicine for treating jaundice and gallstones, but it also invigorates blood circulation, reduces swelling, disperses blood stasis, and relieves pain, treating injuries, carbuncles, and boils. It can also promote urination and relieve strangury, treating painful and turbid urination caused by bladder heat accumulation. The main components of Glechoma hederacea in traditional Chinese medicine include volatile oils, ursolic acid, choline, tannins, and stachyose; it also contains various flavonoids, amino acids, and inorganic salts. It has the effects of promoting diuresis and relieving jaundice, clearing heat and detoxifying, and invigorating blood circulation and reducing swelling. In the late stages of heart failure, edema often occurs due to internal retention of dampness, overflowing into the skin. Glechoma hederacea is considered cool in traditional Chinese medicine, and its powerful diuretic and dampness-removing effects can effectively eliminate edema and reduce the burden on the heart. According to the traditional Chinese medicine theory of "blood and water sharing the same origin," stagnation of dampness inevitably leads to poor blood circulation. Promoting diuresis can invigorate blood circulation, thereby improving the blood stasis state in heart failure. Therefore, by adding Lysimachia christinae to invigorate blood circulation and promote diuresis, the symptoms of edema and shortness of breath in chronic heart failure can be effectively relieved.

[0010] Rhubarb (Dioscorea opposita) is bitter, pungent, and cool in nature, and enters the lung and large intestine meridians. Its bitter and cold properties allow it to descend, while its pungent nature disperses stagnation. Entering the lung and large intestine meridians, it excels at clearing heat and cooling the blood. It clears heat and detoxifies, cools the blood and stops bleeding, making it a commonly used medicine for treating lung heat cough with blood, carbuncles, and boils. It also kills parasites, relieves itching, and promotes bowel movements, treating tinea, eczema, and constipation due to heat accumulation. It can also expel pathogens through purgation, treating syndromes of internal heat accumulation. The main components of rhubarb in traditional Chinese medicine include anthraquinone compounds, tannins, gallic acid, starch, and various vitamins. It has the effects of clearing heat and detoxifying, cooling the blood and stopping bleeding, killing parasites and promoting bowel movements. In the course of heart failure, if accompanied by heat toxicity or blood stasis, the condition can worsen. Rhubarb is considered cool in traditional Chinese medicine, and its heat-clearing and blood-cooling properties can clear heat toxicity from the blood, while its bowel-regulating function can also guide heat downwards. According to the traditional Chinese medicine theories of "the lungs and large intestine are internally and externally related" and "when the qi of the internal organs flows smoothly, the qi of the heart descends," using rhubarb to maintain the smooth flow of qi in the internal organs helps reduce chest cavity pressure and improve cardiopulmonary function. Therefore, adding rhubarb to compound prescriptions, through clearing heat and unblocking the bowels, can assist in the treatment of chronic heart failure complicated by heat accumulation.

[0011] Saxifraga stolonifera is bitter, pungent, and cold in nature, and enters the lung and liver meridians. It is strong in clearing heat and detoxifying, and enters the lung and liver meridians, making it a good remedy for sores and swelling. It clears heat and detoxifies, cools the blood and reduces swelling, making it an excellent medicine for treating carbuncles, boils, and lung abscesses with purulent sputum. It also dispels wind and clears heat, clears the liver and drains fire, treating wind-heat cough and red eyes due to liver heat. Furthermore, it can promote the eruption of rashes through its dispersing effect, treating itchy rashes. The main components of Saxifraga stolonifera in traditional Chinese medicine include alkaloids, flavonoid glycosides, arbutin glycosides, volatile oils, and organic acids. It has the effects of clearing heat and detoxifying, cooling the blood and reducing swelling, and dispelling wind and clearing the liver. Heart failure, if induced by external pathogens or internal heat toxins, can manifest as symptoms such as phlegm-heat obstructing the lungs. Saxifraga stolonifera is cold in traditional Chinese medicine, and its characteristic of specifically entering the lung meridian and being good at clearing heat effectively clears lung heat, resolves phlegm, and relieves asthma. According to the traditional Chinese medicine concept that "heart failure with cough and asthma is often due to lung problems," clearing lung heat and resolving phlegm helps to promote the flow of Qi and reduce the burden on the heart and lungs. Therefore, by adding Saxifraga stolonifera to clear the lungs and detoxify, it can effectively treat cough and asthma caused by chronic heart failure complicated by lung infection or excessive phlegm and heat.

[0012] Small-flowered Qingfengteng is bitter and pungent in nature, neutral in taste, and enters the liver meridian. It is bitter and pungent in nature, slightly cooling in nature, and specifically enters the liver meridian, effectively dispelling wind and unblocking the meridians. It dispels wind and dampness, unblocks the meridians and relieves pain, making it a commonly used medicine for treating rheumatic pain and muscle contractures. It also invigorates blood circulation, reduces swelling, promotes diuresis and eliminates dampness, treating injuries from falls, edema, and beriberi. Furthermore, it can benefit joints by relaxing muscles and tendons, treating numbness in the limbs. The main components of the Chinese medicinal herb Small-flowered Qingfengteng include Qingfengteng alkaloids, various alkaloids, saponins, and volatile oils. It has the effects of dispelling wind and dampness, unblocking the meridians and relieving pain, and invigorating blood circulation and promoting diuresis. "Meridians obstructed" in heart failure is closely related to the liver's function of regulating qi and blood flow. Small-flowered Qingfengteng is considered neutral in traditional Chinese medicine, and its effects of relaxing muscles and tendons, invigorating blood circulation and promoting diuresis can assist the liver in regulating qi and blood flow. According to the traditional Chinese medicine theory that "when liver qi flows smoothly, the heart vessels are unobstructed," soothing the liver and unblocking the meridians helps relieve stagnation in the heart vessels and improve circulation. Therefore, by adding *Clematis chinensis* (small-flowered vine) to promote blood circulation and diuresis, it can be used as an adjunct treatment for chronic heart failure accompanied by limb swelling and pain, and rib distension.

[0013] Pteris vittata is bland and slightly bitter in nature, cold in taste, and enters the liver, stomach, and lung meridians. Its bland and bitter properties promote diuresis and clear heat, making it particularly effective in clearing heat and promoting diuresis. It clears heat and promotes diuresis, cools the blood and stops bleeding, making it an essential medicine for treating damp-heat dysentery, diarrhea, and urinary tract infections. It also clears heat and detoxifies, reduces swelling and dissipates nodules, treating carbuncles, boils, and sore throats. Furthermore, it can reduce jaundice by clearing the liver and gallbladder, treating damp-heat jaundice. The medicinal herb Pteris vittata mainly contains flavonoids, phenols, sterols, amino acids, and tannins. It has the effects of clearing heat and promoting diuresis, cooling the blood and stopping bleeding, detoxifying and reducing swelling. In heart failure, internal dampness easily stagnates and transforms into heat, forming a syndrome of internal damp-heat. Pteris vittata is cold in the four natures of Chinese medicine; its heat-clearing and diuretic effects can guide the damp-heat of heart failure out through urination, providing an outlet for the pathogenic factors. According to the traditional Chinese medicine theory that "when dampness is eliminated, the Qi mechanism will naturally flow smoothly," clearing damp heat helps restore the function of the middle Jiao (middle burner) and reduce the pressure of excess dampness on the heart and lungs. Therefore, by adding Pteris vittata to clear heat and promote diuresis, it can effectively treat chronic heart failure complicated by damp heat, characterized by scanty dark urine and a yellow, greasy tongue coating.

[0014] Scutellaria baicalensis is bitter and cold in nature, and enters the lung, gallbladder, spleen, large intestine, and small intestine meridians. Its bitterness dries dampness, and its coldness clears heat, especially effective in clearing heat from the upper burner, making it a key herb for clearing heat and drying dampness. It clears heat and dries dampness, purges fire and detoxifies, making it the first choice for treating damp-heat syndrome, summer-heat, and lung-heat cough. It also cools the blood and stops bleeding, clears heat and calms the fetus, treating hematemesis and epistaxis due to blood heat, and threatened abortion. It can also reduce fever by clearing the lesser yang meridian, treating alternating chills and fever. The main components of Scutellaria baicalensis in traditional Chinese medicine include flavonoids such as baicalin, baicalein, and wogonin, as well as volatile oils and amino acids. It has the effects of clearing heat and drying dampness, purging fire and detoxifying, cooling the blood and stopping bleeding. During heart failure, excessive heart fire or phlegm-heat disturbing the heart can lead to restlessness and worsened palpitations. Scutellaria baicalensis is cold in traditional Chinese medicine, and its effect of clearing heart fire and lung heat is significant, relieving the interference of heat evil on the mind. According to the traditional Chinese medicine theories that "all pain, itching, and sores belong to the heart" and "when heart fire is reduced, lung metal is cleared," clearing heart fire helps calm the mind and regulate lung qi, thereby stabilizing heart failure. Therefore, by adding Scutellaria baicalensis to purge fire and detoxify, it can effectively treat chronic heart failure accompanied by symptoms of heat such as irritability, dry mouth, and yellow phlegm.

[0015] Phellodendron bark is bitter and cold in nature, and enters the kidney, bladder, and large intestine meridians. Its bitter and cold nature makes it effective in clearing damp-heat in the lower burner, effectively reducing deficiency heat and controlling ministerial fire. It clears heat and dries dampness, drains fire and detoxifies, making it an excellent medicine for treating leukorrhea, urinary tract infections, and beriberi caused by damp-heat accumulation in the lower burner. It also reduces deficiency heat and controls ministerial fire, treating bone-steaming fever, night sweats, and seminal emission caused by yin deficiency and fire excess. Furthermore, it can strengthen yin and preserve body fluids, treating yin deficiency with damp-heat syndrome. The medicinal herb Phellodendron bark mainly contains various alkaloids such as berberine, berberine, and berberine, as well as flavonoids and sterols. It has the effects of clearing heat and drying dampness, draining fire and detoxifying, and reducing fever and eliminating steaming sensations. In cases of prolonged heart failure, yang deficiency can affect yin, leading to complex syndromes of yin deficiency with internal heat or deficiency fire flaring upwards. Phellodendron bark is cold in nature among the four properties of Chinese medicine, and its unique ability to clear both excess fire and deficiency heat makes it particularly suitable for late-stage heart failure with both underlying deficiency and superficial excess, and the coexistence of damp-heat and yin deficiency. According to the traditional Chinese medicine theory that "purging fire is preserving yin," using Phellodendron bark to clear heat from the lower burner can protect kidney yin and strengthen the foundation, indirectly nourishing heart yin. Therefore, by adding Phellodendron bark to purge fire and strengthen yin, it can treat chronic heart failure accompanied by symptoms such as vexation, insomnia, hot flashes, and scanty dark urine.

[0016] Andrographis paniculata is bitter and cold in nature, and enters the heart, lung, large intestine, and bladder meridians. Its bitter and cold properties have a strong ability to clear heat and detoxify, especially effective in clearing heat from the heart and lungs. It clears heat and detoxifies, cools the blood and reduces swelling, making it an excellent remedy for the initial stages of febrile diseases and coughs and asthma due to lung heat. It also dries dampness and stops dysentery, clears heat and promotes urination, treating damp-heat diarrhea and painful urination due to heat. Furthermore, its bitter and cold properties directly counteract the heat and detoxify, treating boils, carbuncles, and snake bites. The medicinal herb Andrographis paniculata mainly contains diterpenoids such as andrographolide and dehydrated andrographolide, as well as flavonoids and organic acids. It has the effects of clearing heat and detoxifying, cooling the blood and reducing swelling, and drying dampness and promoting urination. Traditional Chinese medicine believes that acute exacerbations of heart failure often manifest as symptoms of "phlegm-heat obstructing the lungs" or "heat entering the pericardium." Andrographis paniculata, classified as cold in traditional Chinese medicine, specifically enters the heart and lung meridians, exhibiting remarkable effects in clearing heat and detoxifying, cooling the blood and reducing swelling, directly addressing the progression of the disease. According to the TCM principle of "treating the symptoms in acute cases," a large dose of Andrographis paniculata is used on the basis of tonifying qi and warming yang to clear the heart and lungs, detoxify and promote diuresis, rapidly controlling infection and reducing the damage of inflammation to the heart. Therefore, by adding Andrographis paniculata to clear heat and detoxify, it can effectively treat acute exacerbations of chronic heart failure with severe heat toxicity.

[0017] In summary, the traditional Chinese medicine composition made from a variety of herbs, including Lysimachia christinae, Rheum palmatum, Saxifraga stolonifera, Clematis armandii, Pteris vittata, Scutellaria baicalensis, Phellodendron chinense, and Andrographis paniculata, in a specific ratio, can comprehensively enhance myocardial contractility, improve myocardial energy metabolism, reduce cardiac load, and inhibit excessive neuroendocrine activation through the synergistic effects of multiple targets and pathways. This demonstrates its unique therapeutic advantages in the treatment of specific diseases such as coronary heart disease-related heart failure.

[0018] Preferably, the mass ratio is calculated as follows: Glechoma hederacea: Rheum palmatum: Saxifraga stolonifera: Clematis armandii: Pteris vittata: Scutellaria baicalensis: Phellodendron amurense: Andrographis paniculata = 0.9~1.1: 0.9~1.1: 0.9~1.1: 0.9~1.1: 0.9~1.1: 0.9~1.1: 0.9~1.1: 0.9~1.1.

[0019] Preferably, the traditional Chinese medicine composition comprises, by weight, 15.0-26.6 parts of Lysimachia christinae, 19.5-22.2 parts of Rheum palmatum, 17.0-23.5 parts of Saxifraga stolonifera, 12.0-33.3 parts of Clematis armandii, 13.0-30.7 parts of Pteris vittata, 13.0-30.7 parts of Scutellaria baicalensis, 12.0-33.3 parts of Phellodendron chinense, and 15.0-26.6 parts of Andrographis paniculata.

[0020] Preferably, the traditional Chinese medicine composition comprises, by weight, 20.0 parts of Lysimachia christinae, 20.0 parts of Rheum palmatum, 20.0 parts of Saxifraga stolonifera, 20.0 parts of Clematis armandii, 20.0 parts of Pteris multifida, 20.0 parts of Scutellaria baicalensis, 20.0 parts of Phellodendron chinense, and 20.0 parts of Andrographis paniculata.

[0021] Preferably, the daily dosage of the traditional Chinese medicine composition is 0.2-0.7g / day. More preferably, it is 0.5g / day.

[0022] Preferably, the method for preparing the traditional Chinese medicine composition includes the following steps: mixing the raw materials used to prepare the traditional Chinese medicine composition with a solvent and heating under reflux.

[0023] Preferably, the reflux temperature is 115~119℃ and the reflux time is 4~6 hours.

[0024] Preferably, heart failure includes chronic heart failure.

[0025] According to another aspect of the present invention, a traditional Chinese medicine composition is provided for use in the preparation of a medicament for enhancing myocardial cell vitality and / or enhancing cardiac pumping capacity and / or enhancing myocardial oxygen supply capacity. The traditional Chinese medicine composition comprises, by weight, *Glechoma hederacea*, *Rheum palmatum*, *Saxifraga stolonifera*, *Clematis chinensis*, *Pteris vittata*, *Scutellaria baicalensis*, *Phellodendron chinense*, and *Andrographis paniculata*; and by mass ratio, *Glechoma hederacea*: *Rheum palmatum*: *Saxifraga stolonifera*: *Clematis chinensis*: *Pteris vittata*: *Scutellaria baicalensis*: *Phellodendron chinense*: *Andrographis paniculata* = 30~54: 39~45: 34~47: 24~67: 26~62: 26~62: 24~67: 30~54.

[0026] Preferably, the mass ratio is calculated as follows: Glechoma hederacea: Rheum palmatum: Saxifraga stolonifera: Clematis armandii: Pteris vittata: Scutellaria baicalensis: Phellodendron amurense: Andrographis paniculata = 0.9~1.1: 0.9~1.1: 0.9~1.1: 0.9~1.1: 0.9~1.1: 0.9~1.1: 0.9~1.1: 0.9~1.1.

[0027] Preferably, the traditional Chinese medicine composition comprises, by weight, 15.0-26.6 parts of Lysimachia christinae, 19.5-22.2 parts of Rheum palmatum, 17.0-23.5 parts of Saxifraga stolonifera, 12.0-33.3 parts of Clematis armandii, 13.0-30.7 parts of Pteris vittata, 13.0-30.7 parts of Scutellaria baicalensis, 12.0-33.3 parts of Phellodendron chinense, and 15.0-26.6 parts of Andrographis paniculata.

[0028] Preferably, the traditional Chinese medicine composition comprises, by weight, 20.0 parts of Lysimachia christinae, 20.0 parts of Rheum palmatum, 20.0 parts of Saxifraga stolonifera, 20.0 parts of Clematis armandii, 20.0 parts of Pteris multifida, 20.0 parts of Scutellaria baicalensis, 20.0 parts of Phellodendron chinense, and 20.0 parts of Andrographis paniculata.

[0029] It should be noted that disease treatment emphasizes "syndrome differentiation and treatment" and "disease-symptom correspondence." Different diseases have different locations and underlying mechanisms, leading to fundamental differences in treatment methods and prescription principles. Heart failure is located in the heart, and its core pathogenesis is deficiency of heart and kidney yang, blood stasis, and water retention, belonging to the syndrome of deficiency in the root and excess in the branch. The key to treatment lies in tonifying qi and warming yang to support the root, and promoting blood circulation and diuresis to eliminate pathogenic factors. The traditional Chinese medicine composition involved in this invention targets this unique pathological link of heart failure, aiming to directly regulate cardiac function and hemodynamics, and improve the state of yang deficiency, water retention, and blood stasis. Its therapeutic target and level of action are completely different from the application direction of prescriptions targeting liver and gallbladder damp-heat, qi stagnation, phlegm accumulation, and other pathogenesis. Therefore, the use of this composition for heart failure is not a simple conversion of other known indications, but a new and specific therapeutic development based on a deep understanding of the traditional Chinese medicine pathogenesis of heart failure. Attached Figure Description

[0030] Figure 1 The results are from the model cardiomyocyte activity test in Example 2 of this invention.

[0031] Figure 2 The results are the relative ejection fraction test results of mice in Example 3 of this invention.

[0032] Figure 3 The results of the left ventricular thickness test in mice in Example 3 of this invention are shown. Detailed Implementation

[0033] To enable those skilled in the art to better understand the technical solutions of this invention, the technical solutions of this invention will be clearly and completely described below with reference to the embodiments and accompanying drawings. Obviously, the described embodiments are only some embodiments of this invention, and not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of this invention.

[0034] Example 1: Preparation of the Traditional Chinese Medicine Composition The method for preparing traditional Chinese medicine compositions includes the following steps.

[0035] Preparation of raw materials: The raw materials for preparing the traditional Chinese medicine composition include 20.0 parts of Lysimachia christinae, 20.0 parts of Rheum palmatum, 20.0 parts of Saxifraga stolonifera, 20.0 parts of Clematis armandii, 20.0 parts of Pteris multifida, 20.0 parts of Scutellaria baicalensis, 20.0 parts of Phellodendron chinense, and 20.0 parts of Andrographis paniculata.

[0036] Mix all raw materials with solvent, heat and reflux 3-4 times at a reflux temperature of 117±2℃ for 4-6 hours, filter, combine the filtrates, and concentrate the filtrate to obtain the traditional Chinese medicine composition.

[0037] Example 2: Cellular function test of the traditional Chinese medicine composition To evaluate the cardioprotective effect of the drug on a heart failure model, this embodiment uses a cardiomyocyte model induced to differentiate for 15 days. The cardiomyocyte model is continuously cultured in T75 culture flasks or cultured after resuscitation, ensuring that the culture time is not less than one month to maintain the stability of cell function.

[0038] Cell plating: First, wash cells twice with 1640 basal medium, then add 8 mL of digestion solution and digest at 37°C. Once the cells become loose, gently pipette them off the bottom of the flask. Add 1640 medium to stop the digestion reaction, transfer the resulting cell suspension to a 50 mL centrifuge tube, and centrifuge at 210 g for 5 minutes. After removing the supernatant, resuspend the cell pellet in resuscitation solution, and take 10 μL for cell counting. Then, seed cells at a density of 20,000 per well in 96-well plates, with 90 μL of medium per well. Three parallel blank control wells were set up, with only an equal volume of resuscitation solution added and no cells seeded.

[0039] On the third day of culture, the culture medium was changed: the original resuscitation solution was removed, and the medium was washed twice with 1640 medium, followed by the addition of experimental medium containing different concentrations of drugs.

[0040] The experimental setup includes: ① Negative control group: An equal volume of myocardial cell culture medium was used as a negative control.

[0041] ② Positive control group: 10 μM dexamethasone injection was used as the positive control.

[0042] ③ Gradient concentration groups: The traditional Chinese medicine composition was prepared into 6 concentration groups, with concentrations of 400ng / mL, 133.33ng / mL, 44.44ng / mL, 14.81ng / mL, 4.94ng / mL and 1.65ng / mL respectively.

[0043] Cell viability assay: Four days after drug treatment, cell viability was assessed using PrestoBlue reagent. Before assay, the reagent was equilibrated to room temperature. An appropriate amount of reagent was added to the 96-well plate under light-protected conditions, and then incubated at 37°C for 1 hour in the dark. Before using the microplate reader to detect cell viability, the instrument was preheated for 30 minutes according to the procedure to ensure normal operation. The excitation wavelength was set to 560 nm and the emission wavelength to 590 nm. The output file format and save path were checked to ensure consistent assay conditions.

[0044] Results analysis: such as Figure 1 As shown, under different concentrations (400 ng / mL, 133.33 ng / mL, 44.44 ng / mL, 14.81 ng / mL, 4.94 ng / mL, and 1.65 ng / mL), the cell activity of the model cardiomyocytes treated with the traditional Chinese medicine composition of this invention was significantly higher than that of the negative control group, but there was no significant difference compared with the positive control group. These results indicate that the traditional Chinese medicine composition provided by this invention can enhance cardiomyocyte viability, help improve myocardial oxygen supply capacity, improve microcirculation, and resist myocardial ischemia-reperfusion injury, thus demonstrating good potential in improving cardiac function and treating heart failure.

[0045] Example 3: Animal Experiment of Mouse Aortic Arch Constriction Model Animal model establishment Four-week-old SPF-grade male Kunming (KM) mice were selected as experimental subjects. Before surgery, the mice were weighed and anesthetized via intraperitoneal injection of sodium pentobarbital at a dose of 40 mg / kg. After anesthesia took effect, the mice were fixed in a supine position on the surgical board. The preparation area was defined as the region between the upper edge of the clavicle and the lower edge of the xiphoid process, and between the left mid-axillary line and the anterior midline. Fine sutures were used to retract the oral cavity to maintain airway patency, and the surgical area was illuminated by a cold-light gooseneck lamp.

[0046] Gently pull the tongue out of the mouth, and use a tongue depressor to gently lift the base of the tongue, revealing a translucent area at the tracheal opening in the pharynx. Then, insert a homemade endotracheal tube and connect it to a small animal ventilator, setting the respiratory rate to 90-100 breaths / minute and the tidal volume to 0.3-0.4 mL. After intubation, position the mouse in a right lateral decubitus position to fully expose the left thoracic cavity.

[0047] After disinfecting the surgical area with povidone-iodine, a 7 mm incision was made in the left second intercostal space. The tissues were dissected layer by layer to expose the aortic arch, brachiocephalic artery, and the bifurcation of the left common carotid artery. Aortic arch ligation was performed using 5-0 silk braided sutures wrapped around the aortic arch and a self-made L-shaped 26G ligation needle, completing the aortic arch coarsening procedure. The sham surgery group only underwent open-chest surgery without aortic coarsening. Chest closure was performed using 4-0 suture needles, suturing layer by layer. The incision was disinfected postoperatively.

[0048] Postoperative care and model screening Postoperatively, mice were left in an endotracheal tube for trial weaning. If their breathing was stable, they were completely weaned off the ventilator; if their breathing was slow, the duration of assisted ventilation was appropriately extended. To maintain body temperature, mice were placed on an electric blanket until they regained consciousness, after which they were moved to a rearing cage and given free access to water. Intraoperative and postoperative animal mortality was recorded, and autopsies were performed on deceased individuals to analyze the cause of death. A blood flow velocity greater than 2400 mm / s at the aortic arch constriction was used as the criterion for successful modeling; only animals meeting this criterion were included in subsequent studies.

[0049] Experimental Design A total of 60 C57BL / 6 mice were used in the experiment. The ambient temperature was controlled at 20-25℃, and the light-dark cycle was 12 hours. After the operation, the surviving mice were randomly divided into 4 groups, with no fewer than 10 mice in each group, and were treated as follows: ① Blank solvent control group: 200 μL of blank solvent (physiological saline) was administered by gavage daily for 1 month, and the patients were continuously observed.

[0050] ② Experimental Group A: 200 μL of drug solution containing digoxin at a concentration of 6.5 μg / mL was administered by gavage daily for 1 month, and the patients were continuously observed.

[0051] ③ Experimental Group B: 200 μL of drug solution containing 100 μg / mL spironolactone was administered by gavage daily for 1 month, and the patients were continuously observed.

[0052] ④ Experimental Group C: 200 μL of a traditional Chinese medicine composition containing 25 mg / mL was administered by gavage daily for one month, and the patients were continuously observed.

[0053] Observation indicators and detection methods The survival time of mice was recorded, and cardiac function was assessed using echocardiography. Using an ultrasound system equipped with a 30 MHz probe, M-mode and two-dimensional ultrasound images were acquired in the short-axis and long-axis sections along the left parasternal border under isoflurane anesthesia and in a supine position. Measurement parameters included left ventricular end-systolic diameter, end-diastolic diameter, posterior wall thickness, and anterior wall thickness. Left ventricular weight, fractional shortening, and ejection fraction were calculated based on these parameters. The relative ejection fraction results are shown below. Figure 2 The results of left ventricular thickness measurement are shown in Figure 3 .

[0054] like Figure 2As shown, compared to the blank solvent control group, mice treated with spironolactone, digoxin, or the traditional Chinese medicine composition all showed an increasing trend in left ventricular ejection fraction. However, compared to mice treated with spironolactone and digoxin, the mice in experimental group A treated with the traditional Chinese medicine composition showed a more significant relative increase in left ventricular ejection fraction. This indicates that the composition can more effectively enhance myocardial contractility, increase stroke volume and cardiac output, thereby more comprehensively improving cardiac pumping function, reversing hemodynamic disorders in heart failure, and demonstrating superior therapeutic potential compared to the control drugs spironolactone and digoxin.

[0055] like Figure 3 As shown, compared with mice treated with spironolactone and digoxin, mice in experimental group A treated with the traditional Chinese medicine composition showed a more significant reduction in left ventricular thickness. This indicates that the traditional Chinese medicine composition can more effectively reverse ventricular remodeling and improve cardiac contractile function, thus showing greater potential in the treatment of heart failure.

[0056] The above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. Use of a traditional Chinese medicine composition in the preparation of a medicament for preventing and / or treating heart failure, characterized in that, The traditional Chinese medicine composition comprises: Herba Galium, Radix Rumicis, Saxifraga stolonifera, Smallflowered Sabia, Pteris multifida, Scutellaria baicalensis, Phellodendron amurense, Andrographis paniculata; According to the mass ratio, the Herba Galium: the Radix Rumicis: the Saxifraga stolonifera: the Smallflowered Sabia: the Pteris multifida: the Scutellaria baicalensis: the Phellodendron amurense: the Andrographis paniculata = 30-54: 39-45: 34-47: 24-67: 26-62: 26-62: 24-67: 30-54.

2. The use of the traditional Chinese medicine composition according to claim 1 in the preparation of a medicament for treating heart failure, characterized in that: According to the mass ratio, the Herba Galium: the Radix Rumicis: the Saxifraga stolonifera: the Smallflowered Sabia: the Pteris multifida: the Scutellaria baicalensis: the Phellodendron amurense: the Andrographis paniculata = 0.9-1.1: 0.9-1.1: 0.9-1.1: 0.9-1.1: 0.9-1.1: 0.9-1.1: 0.9-1.1: 0.9-1.

1.

3. The use of the traditional Chinese medicine composition according to claim 1 in the preparation of a medicament for treating heart failure, characterized in that, According to the weight fraction, the traditional Chinese medicine composition comprises: Herba Galium 15.0-26.6 parts, Radix Rumicis 19.5-22.2 parts, Saxifraga stolonifera 17.0-23.5 parts, Smallflowered Sabia 12.0-33.3 parts, Pteris multifida 13.0-30.7 parts, Scutellaria baicalensis 13.0-30.7 parts, Phellodendron amurense 12.0-33.3 parts, Andrographis paniculata 15.0-26.6 parts.

4. The use of the traditional Chinese medicine composition according to claim 1 in the preparation of a medicament for treating heart failure, characterized in that, According to the weight fraction, the traditional Chinese medicine composition comprises: Herba Galium 15.0-26.6 parts, Radix Rumicis 19.5-22.2 parts, Saxifraga stolonifera 17.0-23.5 parts, Smallflowered Sabia 12.0-33.3 parts, Pteris multifida 13.0-30.7 parts, Scutellaria baicalensis 13.0-30.7 parts, Phellodendron amurense 12.0-33.3 parts, Andrographis paniculata 15.0-26.6 parts.

5. The use of the traditional Chinese medicine composition according to any one of claims 1-4 in the preparation of a medicament for treating heart failure, characterized in that: The daily dosage of the traditional Chinese medicine composition is 0.2-0.7 g / day.

6. The use of the traditional Chinese medicine composition according to claim 1 in the preparation of a medicament for treating heart failure, characterized in that, The method for preparing the traditional Chinese medicine composition comprises the following operations: mixing raw materials for preparing the traditional Chinese medicine composition with a solvent and heating to reflux.

7. The use of the traditional Chinese medicine composition according to claim 6 for the preparation of a medicament for treating heart failure, characterized in that, The reflux temperature is 115-120°C, and the reflux time is 4-6 hours.

8. The use of the traditional Chinese medicine composition according to claim 1 in the preparation of a medicament for treating heart failure, characterized in that: The heart failure comprises chronic heart failure.

9. Use of a traditional Chinese medicine composition in the preparation of a medicament for improving the viability of cardiomyocytes and / or improving the pumping capacity of the heart and / or improving the oxygen supply capacity of the myocardium, characterized in that: According to the weight fraction, the traditional Chinese medicine composition comprises: Herba Galium, Radix Rumicis, Saxifraga stolonifera, Smallflowered Sabia, Pteris multifida, Scutellaria baicalensis, Phellodendron amurense, Andrographis paniculata; According to the mass ratio, the Herba Galium: the Radix Rumicis: the Saxifraga stolonifera: the Smallflowered Sabia: the Pteris multifida: the Scutellaria baicalensis: the Phellodendron amurense: the Andrographis paniculata = 30-54: 39-45: 34-47: 24-67: 26-62: 26-62: 24-67: 30-54.

10. The use of the traditional Chinese medicine composition according to claim 9 in the preparation of a medicament for improving the viability of cardiomyocytes and / or improving the pumping capacity of the heart and / or improving the oxygen supply capacity of the myocardium, characterized in that: According to the weight fraction, the traditional Chinese medicine composition comprises: Herba Galium 15.0-26.6 parts, Radix Rumicis 19.5-22.2 parts, Saxifraga stolonifera 17.0-23.5 parts, Smallflowered Sabia 12.0-33.3 parts, Pteris multifida 13.0-30.7 parts, Scutellaria baicalensis 13.0-30.7 parts, Phellodendron amurense 12.0-33.3 parts, Andrographis paniculata 15.0-26.6 parts.

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