Use of a composition for searching wind and resolving stasis in the preparation of a drug for preventing and treating pressure overload-induced cardiac injury

Abstract

This invention belongs to the technical field of traditional Chinese medicine, and relates to the use of a wind-dispelling and nodule-resolving composition, extract, or preparation in the preparation of a medicament for the prevention and / or treatment of stress overload cardiac injury. This invention also provides the use of a wind-dispelling and nodule-resolving composition, extract, or preparation in the preparation of a chemical product for the prevention and treatment of stress overload cardiac injury. The application of a wind-dispelling and nodule-resolving composition in the preparation of a medicament for the prevention and treatment of stress overload cardiac injury provided by this invention represents the first discovery of the protective effect of such a composition against stress overload cardiac injury, providing a new traditional Chinese medicine treatment option for the prevention and / or treatment of stress overload cardiac injury.

Description

Technical Field

[0001] This invention belongs to the technical field of traditional Chinese medicine, and relates to the application of wind-dispelling and nodule-resolving compositions in the preparation of drugs for the prevention and treatment of stress overload-induced cardiac injury. Specifically, it relates to the application of wind-dispelling and nodule-resolving compositions, wind-dispelling and nodule-resolving extracts, and wind-dispelling and nodule-resolving preparations in the preparation of drugs for the prevention and / or treatment of stress overload-induced cardiac injury. Background Technology

[0002] Pressure overload (PO) cardiac injury is a common heart condition caused by aortic stenosis, aortic coarctation, or long-term hypertension. It can lead to myocardial hypertrophy, myocardial fibrosis, atrial fibrillation, and heart failure, seriously threatening patients' quality of life. Currently, drugs targeting major pressure overload cardiac injury mainly include beta-blockers, ACEIs / ARBs / ARNIs, SGLT2 inhibitors, and aldosterone antagonists. However, these drugs still have limitations in inhibiting cardiac structural remodeling, improving cardiac function, and reducing susceptibility to atrial fibrillation. Transverse aortic coarctation surgery is a classic animal model for studying pressure overload cardiac injury.

[0003] Chinese patent CN110123868B discloses a composition (Soufeng Sanjie Fang) for treating bone erosion in rheumatoid arthritis. The composition comprises the following components by weight: 1.5g of whole scorpion, 1.5g of centipede, 20g of astragalus, and 30g of black soybean husk. This combination is able to inhibit the expression of IL-6 and RANKL in various cells of the joint, increase the expression of osteoprotegerin OPG, reduce the number of osteoclasts, increase bone density, and effectively relieve joint swelling and reduce synovial membrane damage, thereby achieving a therapeutic effect on bone erosion in rheumatoid arthritis.

[0004] However, the aforementioned patents only disclose the use of the Soufeng Sanjie formula in rheumatoid arthritis, without mentioning its application in cardiovascular diseases. Currently, there is no literature or patent regarding the cardiovascular applications of this formula, nor has it revealed its ability to improve cardiac function indicators or reduce atrial fibrillation burden. Summary of the Invention

[0005] In view of the shortcomings of the prior art described above, the purpose of this invention is to provide a new use of the wind-dispersing and nodule-resolving composition in the preparation of a medicament for the prevention and treatment of stress overload-induced cardiac injury, aiming to solve the problem of the lack of effective traditional Chinese medicine solutions for this disease in the prior art.

[0006] To achieve the above and other related objectives, a first aspect of the present invention provides the use of a wind-dispelling and nodule-resolving composition, wind-dispelling and nodule-resolving extract, or wind-dispelling and nodule-resolving preparation in the preparation of a medicament for the prevention and / or treatment of stress overload-induced cardiac injury.

[0007] A second aspect of the present invention provides the use of a wind-dispelling and nodule-resolving composition, wind-dispelling and nodule-resolving extract, or wind-dispelling and nodule-resolving preparation in the preparation of a chemical product for the prevention and / or treatment of stress overload-induced cardiac injury.

[0008] As described above, the application of the present invention in the preparation of medicaments for the prevention and / or treatment of stress overload-induced cardiac injury has the following beneficial effects: (1) In contrast to the prior art, the wind-dispersing and nodule-resolving composition has only been disclosed for the treatment of rheumatoid arthritis, and its application in the field of cardiovascular diseases has not been reported. However, the present invention provides the application of the wind-dispersing and nodule-resolving composition in the preparation of medicaments for the prevention and / or treatment of stress overload cardiac injury, and for the first time discovers the protective effect of the wind-dispersing and nodule-resolving composition on stress overload cardiac injury, and provides the application of the wind-dispersing and nodule-resolving composition in the preparation of products for the prevention and / or treatment of stress overload cardiac injury.

[0009] (2) This invention provides the application of the wind-dispersing and nodule-resolving composition in the preparation of drugs for the prevention and / or treatment of stress overload-induced cardiac injury, while simultaneously improving cardiac structure, the structural and functional damage of various cardiac chambers, susceptibility to atrial fibrillation, cardiac fibrosis, and cardiac electrophysiology, demonstrating the multi-target advantages of traditional Chinese medicine compound. Specifically, it can significantly reduce the increase in left atrial diameter (LA) caused by stress overload, significantly increase left ventricular ejection fraction (LVEF), significantly improve right ventricular function (TAPSE), significantly reduce atrial fibrillation burden (AF burden), reduce myocardial tissue inflammatory infiltration (HE staining), and reduce myocardial fibrosis (Masson staining).

[0010] (3) The present invention provides the application of the wind-dispersing and nodule-resolving composition in the preparation of drugs for the prevention and / or treatment of stress overload heart injury. Compared with existing drugs for heart function impairment, it expands the application of traditional Chinese medicine in cardiovascular diseases, provides a new Chinese medicine treatment plan for the prevention and / or treatment of stress overload heart injury, and provides a new, efficient and economical treatment option for clinical practice. Attached Figure Description

[0011] Figure 1 The graph shows the effect of the Soufeng Sanjie extract on cardiac function in each group of rats. In the graph, A represents the change in left atrial diameter (LA) in each group of rats; B represents the change in ejection fraction (LVEF) in each group of rats; C represents the change in tricuspid annular systolic displacement (TAPSE) in each group of rats; NC represents the control group; PO represents the pressure overload group; and PO+SF-3 represents the pressure overload group using Soufeng Sanjie extract 3# from Example 3. * indicates... p <0.05, ** indicates p <0.01, **** indicates p <0.001.

[0012] Figure 2 The graph shows the effect of the Soufeng Sanjie extract on the induction rate and duration of atrial fibrillation in each group of rats. In the graph, A represents the change in the probability of atrial fibrillation induction in each group, B represents the change in the duration of atrial fibrillation in each group, AF represents atrial fibrillation, SR represents sinus rhythm, NC represents the control group, PO represents the pressure overload group, and PO+SF-3 represents the pressure overload group using Soufeng Sanjie extract 3# from Example 3. * indicates... p <0.05.

[0013] Figure 3 The graphs show the effects of different proportions of the Soufengsanjie extract on cardiac function in each group of rats. A represents the change in tricuspid annular systolic displacement (TAPSE) compared to Soufengsanjie extract 1# from Example 1; B represents the change in tricuspid annular systolic displacement (TAPSE) compared to Soufengsanjie extract 2# from Example 2; C represents the change in tricuspid annular systolic displacement (TAPSE) compared to Soufengsanjie extract 4# from Example 4; NC represents the control group; PO represents the pressure overload group; PO+SF-1 represents the pressure overload group using Soufengsanjie extract 1# from Example 1; PO+SF-2 represents the pressure overload group using Soufengsanjie extract 2# from Example 2; PO+SF-4 represents the pressure overload group using Soufengsanjie extract 4# from Example 4; * indicates... p <0.05, ** indicates p <0.01, **** indicates p <0.001.

[0014] Figure 4 The diagram shows the effect of the Soufeng Sanjie extract on the pathological structure of the heart tissue of rats in each group. Among them, A is the masson stained section of rats in the NC group, B is the masson stained section of rats in the PO group, and C is the masson stained section of rats in the PO+SF-3 group. Detailed Implementation

[0015] Based on extensive practical research, the inventors of this invention have developed a wind-dispelling and nodule-resolving composition, extract, or preparation that can prevent and treat stress-induced cardiac injury.

[0016] The first aspect of the present invention provides the use of a wind-dispelling and nodule-resolving composition, wind-dispelling and nodule-resolving extract, or wind-dispelling and nodule-resolving preparation as an active ingredient in the preparation of a medicament for the prevention and / or treatment of stress overload-induced cardiac injury.

[0017] In the above-mentioned uses, the wind-dispelling and nodule-dispersing composition comprises the following components by weight: 20-40 parts black soybean husk; 20-30 parts astragalus; 0.5-1.5 parts scorpion; and 0.5-1.5 parts centipede.

[0018] The wind-dispersing and lumpy-dissolving composition provided by this invention may include 20-30 parts, 30-35 parts, or 35-40 parts of black soybean hulls by weight. Specifically, the weight percentages of the black soybean hulls include, but are not limited to, 20 parts, 30 parts, 35 parts, or 40 parts. Generally, the black soybean hulls are from soybean (Soybean). Glycine max (L.) Merr. The dried, mature black seed coat. It has the effects of nourishing yin and blood, clearing heat and stopping sweating.

[0019] The wind-dispersing and stagnation-resolving composition provided by this invention may include 20-25 parts or 25-30 parts of Astragalus membranaceus by weight, specifically including, but not limited to, 20 parts, 25 parts, or 30 parts by weight. Generally, the Astragalus membranaceus is Astragalus mongholicus, a plant belonging to the genus Astragalus of the legume family. Astragalus membranaceus (Fisch.) Bge. Var. mongholicus (Bge.) Hsiao or Astragalus membranaceus Astragalus membranaceus (Fisch.) Bge. The dried root of the plant has the effects of tonifying qi and raising yang, consolidating the exterior and stopping sweating, promoting diuresis and reducing swelling, generating fluids and nourishing blood, promoting blood circulation and relieving pain, promoting detoxification and draining pus, and promoting wound healing and tissue regeneration.

[0020] The wind-dispersing and stagnation-resolving composition provided by this invention may include 0.5-1 parts or 1-1.5 parts of whole scorpion by weight. Specifically, the weight of whole scorpion includes, but is not limited to, 0.5 parts, 1 part, and 1.5 parts. Generally, the whole scorpion is *Scorpionus spp.*, an animal belonging to the genus *Scorpionus* of the family Scorpionidae. Buthus martensii Karsch The dried form. It has the effects of calming wind and relieving spasms, attacking toxins and dispersing nodules, and clearing the meridians and relieving pain.

[0021] The wind-dispersing and lumpy-dissolving composition provided by this invention may include 0.5-1 parts or 1-1.5 parts of centipede by weight. Specifically, the mass fraction of centipede includes, but is not limited to, 0.5 parts, 1 part, and 1.5 parts. Generally, the centipede is *Scolopendra subspinipes*, an animal belonging to the genus *Scolopendra* of the family Scolopendra. Scolopendra subspinipes mutilans L.Koch The dried form. It has the effects of calming wind and relieving spasms, clearing the meridians and relieving pain, and attacking toxins and dispersing nodules.

[0022] In a preferred embodiment of the present invention, the wind-dispelling and nodule-dispersing composition comprises the following components by mass: 20 parts black soybean husk; 30 parts astragalus; 1 part scorpion; and 0.5 parts centipede.

[0023] In a preferred embodiment of the present invention, the wind-dispelling and nodule-dispersing composition comprises the following components by mass: 40 parts black soybean husk; 25 parts astragalus; 0.5 parts scorpion; and 1 part centipede.

[0024] In a preferred embodiment of the present invention, the wind-dispelling and nodule-dispersing composition comprises the following components by mass: 30 parts black soybean husk; 20 parts astragalus; 1.5 parts scorpion; and 1.5 parts centipede.

[0025] In a preferred embodiment of the present invention, the wind-dispelling and nodule-resolving composition comprises the following components by mass: 35 parts black soybean husk; 20 parts astragalus; 1 part scorpion; and 1 part centipede.

[0026] In the wind-dispelling and nodule-dispersing composition provided by the present invention, the above-mentioned medicinal materials are natural medicinal materials, which can be purchased from ordinary pharmacies or Chinese medicine sales companies, and all comply with national pharmaceutical standards or relevant regulations such as the Chinese Pharmacopoeia.

[0027] The wind-dispersing and stagnation-resolving composition of the medicines formulated in this invention for the prevention and / or treatment of stress overload-induced cardiac injury fully complies with the principles of syndrome differentiation and treatment in traditional Chinese medicine.

[0028] Black soybean husks, being black in color, enter the kidney meridian. Their light and clear nature also benefits the pericardium. Sweet and cool in nature, they nourish yin, thus suppressing deficient yang by nourishing kidney yin. The kidneys are the mother of the heart; nourishing kidney water nourishes the heart, and heart yin is the material basis for cardiac function. Nourishing the kidneys provides material support for the repair of damaged myocardium. Furthermore, black soybean husks also enter the liver meridian, nourishing liver blood and calming the liver to extinguish wind. The palpitations associated with atrial fibrillation are considered to be caused by internal wind-evil; black soybean husks, by nourishing liver blood, achieve the effect of calming the liver and extinguishing wind, thereby reducing atrial fibrillation attacks.

[0029] Among them, Astragalus membranaceus, with its yellow and white color resembling the spleen and lung meridians, is a sacred medicine for tonifying Qi. It nourishes the Qi of the spleen and lungs, thus providing the source for the production of Qi and blood. The spleen is the source of Qi and blood production, and the lungs govern Qi and govern all the blood vessels. When the Qi of the spleen and lungs is strong, the ancestral Qi is sufficient. The ancestral Qi accumulates in the chest, flows through the heart vessels, and governs respiration, thus directly enhancing the heart's pumping function.

[0030] Both scorpions and centipedes are salty, pungent, and neutral in nature, with slight toxicity. Saltiness softens hardness, and pungency disperses stagnation. Insects are adept at moving, and their effects include calming wind and stopping spasms, clearing the channels and relieving pain, and attacking toxins and dispersing nodules. Their penetrating nature surpasses that of herbs, allowing them to directly enter the heart's meridians and eliminate latent pathogens hidden within the collaterals. Long-term stress leads to myocardial interstitial fibrosis and tissue stiffness, falling under the category of "phlegm and blood stasis intertwined, collateral masses." These masses are hard and tangible, deeply hidden within the collaterals, and cannot be dispersed by ordinary blood-activating and phlegm-resolving remedies. Scorpions, utilizing their penetrating nature, penetrate deep into the heart's collaterals, clearing wind and eliminating stagnation, resolving the phlegm and blood stasis, dispersing existing masses, and preventing the recurrence of unformed masses.

[0031] It is evident that the four herbs each perform their specific functions, working synergistically to enhance efficacy. Astragalus replenishes Qi to promote the circulation of Qi and blood, while black soybean coat nourishes Yin to moisten the myocardium. When Qi is abundant, Yin fluids are naturally generated, and when Yin is sufficient, Qi has a foundation. Together, they work to repair damaged myocardium. Black soybean coat nourishes the kidneys, calms Yang, and extinguishes wind in the liver to eliminate the source of internal wind. Scorpion and centipede directly penetrate the collaterals, dispel wind, and stop spasms to eliminate pathogenic factors. Treating both internal and external ailments, they effectively reduce susceptibility to atrial fibrillation. By employing the principle of complementary combinations to resolve myocardial collateral obstruction, they effectively prevent and treat stress-induced cardiac damage and reduce the risk of atrial fibrillation and other related heart diseases.

[0032] It is particularly important to point out that stress-induced cardiac injury differs fundamentally from other common cardiac injuries in terms of symptoms and treatment. From a Traditional Chinese Medicine (TCM) perspective, it represents an extreme state of "excessive exertion leading to depletion of Qi," with the core pathogenesis being "deficiency of Zong Qi, insufficiency of Heart Yin, phlegm and blood stasis forming masses, and floating of deficient Yang combined with internal stirring of Liver Wind." From a Western medical perspective, it corresponds to persistent increase in mechanical afterload, diffuse interstitial fibrosis, and chronic atrial fibrillation matrix. Pathologically, it presents a unique progression of concentric hypertrophy, diffuse interstitial fibrosis, and decompensated heart failure, initiated by persistent increase in mechanical afterload. Clinically, it manifests as progressive dyspnea and decreased exercise tolerance. Furthermore, due to increased left atrial pressure and diffuse atrial fibrosis, susceptibility to atrial fibrillation is significantly increased and is characterized by its chronic and easily maintained nature.

[0033] In the above-mentioned uses, the preparation of the wind-dispelling and nodule-resolving extract includes: taking black bean husks and astragalus according to the proportion of the wind-dispelling and nodule-resolving composition, soaking them in water, decocting them, cooling them, filtering them, adding whole scorpion and centipede powder to the obtained filtrate, and mixing them well to obtain the extract.

[0034] In the wind-dispersing and stagnation-resolving extract provided by this invention, the amount of water added is sufficient to completely submerge the black bean husks and astragalus, with the water level 2-3 cm above the submerged water level.

[0035] In the wind-dispersing and nodule-resolving extract provided by this invention, the soaking time in water is 20-40 minutes, preferably 30 minutes.

[0036] In the wind-dispersing and nodule-resolving extract provided by this invention, the decoction is performed 1-3 times, preferably 2 times.

[0037] In the wind-dispersing and nodule-resolving extract provided by this invention, the decoction time is 1-2 hours each time.

[0038] In the wind-dispersing and stagnation-resolving extract provided by this invention, filtration is required after each decoction.

[0039] In the wind-dispersing and necrotic extract provided by the present invention, the filtration is performed by sieving through a sieve, wherein the mesh size of the sieve is ≤0.5mm.

[0040] In the wind-dispersing and stagnation-resolving extract provided by the present invention, the filtrate is the filtrate obtained by filtration and combination after at least one decoction.

[0041] In the wind-dispersing and stagnation-removing extract provided by the present invention, the powders of scorpion and centipede are obtained by grinding and sieving.

[0042] In a preferred embodiment of the present invention, the mesh size of the sieve is not less than 80 mesh, preferably 80 mesh.

[0043] In the above-described uses, the wind-dispelling and nodule-resolving preparation comprises a therapeutically effective amount of a wind-dispelling and nodule-resolving composition, or a therapeutically effective amount of a wind-dispelling and nodule-resolving extract, and one or more conventional pharmaceutically acceptable excipients.

[0044] In the wind-dispelling and nodule-resolving preparations provided by the present invention, the wind-dispelling and nodule-resolving composition or extract is the sole active ingredient, or one of the active ingredients, and can be mixed with one or more pharmaceutically acceptable excipients to prepare drug dosage forms with different routes of administration.

[0045] Specifically, pharmaceutically acceptable excipients include, but are not limited to, drug-acceptable carriers, diluents, fillers, binders, disintegrants, lubricants, suspending agents, adhesives, sweeteners, flavoring agents, preservatives, and other excipients. Therapeutic inert inorganic or organic carriers known to those skilled in the art include, but are not limited to, lactose, corn starch or derivatives thereof, talc, vegetable oils, waxes, fats, polyhydroxy compounds such as polyethylene glycol, water, sucrose, ethanol, glycerin, and the like. Various flow aids, solvents, sustained-release agents, emulsifiers, absorption enhancers, surfactants, lubricants, dispersants, flavoring agents, humectants, antioxidants, sweeteners, colorants, stabilizers, salts, buffers, and the like may also be added as needed to aid in the stability of the formulation or to contribute to its activity or bioavailability.

[0046] Specifically, the dosage forms of the soothing and dispersing preparations include, but are not limited to, tablets, capsules, powders, granules, pills, syrups, solutions, powders, ointments, drop pills, suspensions, emulsions, oral liquids, liniments, tinctures, aerosols, powder inhalers, injections, sterile powders for injection, or suppositories.

[0047] In the above-described uses, the drug of the present invention can be administered orally, intravenously, intramuscularly, or subcutaneously.

[0048] A second aspect of the present invention provides the use of a wind-dispelling and nodule-resolving composition, wind-dispelling and nodule-resolving extract, or wind-dispelling and nodule-resolving preparation as an active ingredient in the preparation of a chemical product for the prevention and / or treatment of stress overload-induced cardiac injury.

[0049] In the aforementioned applications, the chemical product necessarily comprises a wind-dispersing and nodule-resolving composition, wind-dispersing and nodule-resolving extract, or wind-dispersing and nodule-resolving preparation, with the wind-dispersing and nodule-resolving composition or extract serving as the effective ingredient for the aforementioned functions, specifically, it may be the sole active ingredient. The effective ingredient in the chemical product that performs the aforementioned functions may be solely the wind-dispersing and nodule-resolving composition or extract, or it may include other chemicals that can perform similar functions. The chemical product may be a single-component substance or a multi-component substance. The form of the chemical product is not particularly limited and may be in various forms such as solid, liquid, gel, semi-liquid, or aerosol. The fields in which the chemical product is used may include pharmaceuticals, health products, and food.

[0050] In the use of the first or second aspect of the present invention, the pressure overload cardiac injury is selected from at least one of cardiac structural injury, cardiac function injury, atrial fibrillation susceptibility, fibrosis, failure, electrophysiological abnormality or arrhythmia.

[0051] In the use of the first or second aspect of the present invention, the prevention and / or treatment of stress overload-induced cardiac injury is embodied in at least one of the following aspects: S1) Improves structural and functional damage to various chambers caused by pressure overload; S2) Improves the decrease in left ventricular ejection fraction caused by pressure overload; S3) Improves right ventricular function decline caused by pressure overload; S4) Improves the increased atrial fibrillation load caused by pressure overload; S5) Improves myocardial tissue inflammation caused by stress overload; S6) Improves myocardial fibrosis caused by stress overload.

[0052] In the use of the first or second aspect of this invention, the drug or chemical product is used to treat a human or mammal. The mammal includes, but is not limited to, rats.

[0053] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of protection of the present invention.

[0054] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0055] Before further describing specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terminology used in the embodiments of the present invention is for describing specific embodiments and not for limiting the scope of protection of the present invention; in the specification and claims of the present invention, unless otherwise expressly stated in the text, the singular forms "a", "an" and "this" include the plural forms.

[0056] When numerical ranges are given in the embodiments, it should be understood that, unless otherwise stated in the present invention, both endpoints of each numerical range and any value between the two endpoints may be selected. Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art. In addition to the specific methods, apparatus, and materials used in the embodiments, based on the knowledge of the prior art possessed by one of ordinary skill in the art and the description of this invention, any prior art methods, apparatus, and materials similar to or equivalent to those described, apparatus, and materials in the embodiments of this invention may be used to implement the present invention.

[0057] Unless otherwise specified, the production processes, experimental methods, or testing methods involved in the embodiments and comparative examples of this invention are all conventional methods in the prior art, and their names and / or abbreviations are all conventional names in the art, which are very clear and distinct in the relevant application fields. Those skilled in the art can understand the conventional process steps based on the names and apply the corresponding equipment to implement them according to conventional conditions or conditions recommended by the manufacturer.

[0058] The various instruments, equipment, raw materials, or reagents used in the embodiments of this invention are not subject to any special restrictions on their source. They are all conventional products that can be purchased through legitimate commercial channels and can be prepared according to conventional methods known to those skilled in the art. Specifically, for example, multichannel physiological recorders, air anesthesia machines, dehydrators, embedding machines, pathological sectioning machines, and ultrasound machines are all conventional instruments that can be purchased through legitimate commercial channels.

[0059] Unless otherwise specified, the sources of cells, animals, and drugs involved in the embodiments of this invention are all commercially available.

[0060] Example 1 Take 20g of black soybean husks and 30g of astragalus root, clean them, add water to completely submerge the black soybean husks and astragalus root, ensuring the water level is 2.5cm above the submerged area, soak for 30 minutes, then decoct twice, 1.5 hours each time. After cooling, filter through a 0.5mm sieve and combine the filtrates. Next, take 1g of whole scorpion and 0.5g of centipede, grind them, pass through an 80-mesh sieve, add them to the filtrate, mix well, and obtain the wind-dispersing and nodule-resolving extract #1.

[0061] Example 2 Take 40g of black soybean husks and 25g of astragalus root, clean them, add water to completely submerge the black soybean husks and astragalus root, ensuring the water level is 2.5cm above the submerged area, soak for 30 minutes, then decoct twice, 1.5 hours each time. After cooling, filter through a 0.5mm sieve and combine the filtrates. Next, take 0.5g of whole scorpion and 1g of centipede, grind them, pass through an 80-mesh sieve, add them to the filtrate, mix well, and obtain the Wind-Dispelling and Nodule-Resolving Extract 2#.

[0062] Example 3 Take 30g of black soybean husks and 20g of astragalus root, clean them, add water to completely submerge the black soybean husks and astragalus root, ensuring the water level is 2.5cm above the submerged area, soak for 30 minutes, then decoct twice, 1.5 hours each time. After cooling, filter through a 0.5mm sieve and combine the filtrates. Next, take 1.5g of whole scorpion and 1.5g of centipede, grind them, pass them through an 80-mesh sieve, add them to the filtrate, mix well, and obtain the wind-dispersing and nodule-resolving extract #3.

[0063] Example 4 Take 35g of black soybean husks and 20g of astragalus root, clean them, and then add water to completely submerge the black soybean husks and astragalus root, with the water level 2.5cm above the submerged water level. Decoct twice, 1.5 hours each time. After cooling, filter through a 0.5mm sieve and combine the filtrates. Then, take 1g of whole scorpion and 1g of centipede, grind them, and pass them through an 80-mesh sieve. Add them to the filtrate and mix well to obtain the wind-dispersing and nodule-resolving extract #4.

[0064] Example 5 Take 20g of black soybean husks and 30g of astragalus root, clean them, add water to completely submerge the black soybean husks and astragalus root, ensuring the water level is 3cm above the submerged area, soak for 25 minutes, decoct three times, one hour each time, cool, and filter through a 0.4mm sieve, then combine the filtrates. Next, take 1g of whole scorpion and 0.5g of centipede, grind them, pass them through an 80-mesh sieve, add them to the filtrate, mix well, and obtain the wind-dispersing and nodule-resolving extract #5.

[0065] Example 6 Take 20g of black soybean husks and 30g of astragalus root, clean them, add water to completely submerge the black soybean husks and astragalus root, with the water level 2cm above the submerged area, soak for 35 minutes, decoct once for 2 hours, cool, and filter through a 0.3mm sieve to obtain the filtrate. Then take 1g of whole scorpion and 0.5g of centipede, grind them, pass them through an 80-mesh sieve, add them to the filtrate, mix well, and obtain the wind-dispersing and nodule-resolving extract 6#.

[0066] Test Example 1 1. Preparation (1) Experimental mice: Male SD rats, weighing 160-180g, 3-4 weeks old, SPF grade, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., and housed in the SPF grade laboratory animal room of Shanghai Chengxi Biotechnology Co., Ltd. The experimental temperature was controlled at 25±1℃, and they had free access to water and animal feed. The experiment was conducted after 1 week of acclimatization.

[0067] (2) Setting up experimental groups: control group (NC), pressure overload group (PO) and pressure overload + wind-dispersing extract group (PO+SF) were set up respectively, with 10 rats in each group.

[0068] In each experimental group, except for the blank control group, all other rats underwent surgery. The specific procedure was as follows: After anesthesia, the rats were opened at the 2nd-3rd intercostal space along the left sternal border to expose the aortic arch. An 18G needle was placed parallel to the transverse part of the aortic arch, ligated with 6-0 silk suture, and then withdrawn, causing aortic constriction. The PO+SF group received continuous gavage administration before and after surgery, once daily (containing 1.6g / kg of crude drug), for 21 consecutive days. The NC and PO groups received distilled water by gavage.

[0069] (3) Data were analyzed using Graphpad Prism 10.1.2, and one-way ANOVA was used for comparisons among multiple groups. All p A value less than 0.05 indicates a statistically significant difference.* p <0.05、** p <0.01, *** p <0.001.

[0070] 2. Detection of cardiac function injury in rats The wind-dispersing and nodule-removing extracts from Examples 1-4 were taken as SF in the PO+SF group to form PO+SF-1 group, PO+SF-2 group, PO+SF-3 group and PO+SF-4 group respectively.

[0071] After the last administration of the drug, the PO+SF-1, PO+SF-2, PO+SF-3, and PO+SF-4 groups were deprived of medication for 12 hours prior to the end of the second administration, and cardiac function was assessed using an ultrasound imaging system. Specific methods: Mice were shaved on their chests, induced anesthesia with isoflurane, and then fixed in a supine position on a 37°C constant-temperature physiological platform. Anesthesia was maintained with a low dose of isoflurane. Coupling agent was applied to the anesthetized mice's chests, and a probe was used to obtain the long-axis section of the left ventricle parasternal and the apical four-chamber view to assess cardiac systolic and diastolic function, respectively. The NC and PO groups underwent simultaneous testing. Detailed experimental results are shown below. Figure 1 , Figure 3 .

[0072] Depend on Figure 1 As can be seen, when the PO+SF-3 group was used in the experiment, Figure A shows the left atrial diameter of rats in each group. The experimental results show that the left atrial size was significantly reduced compared with the PO group (**). p <0.01, *** p<0.001). Figure B shows the changes in ejection fraction (LVEF) of rats in each group. Compared with the PO group, the PO+SF-3 group showed a significant improvement in ejection fraction (*). p <0.05, *** p <0.001). Figure C shows the tricuspid annular systolic shift (TAPSE), and the PO+SF-3 group significantly reversed the decrease in right ventricular systolic function. This indicates that the Soufeng Sanjie extract can significantly improve cardiac function impairment in rats.

[0073] Depend on Figure 3 It can be seen that when PO+SF-1 group, PO+SF-2 group, and PO+SF-4 group are selected for the experiment, Figure 3 Figures A, B, and C show the tricuspid annular systolic shift (TAPSE) in each group of rats. The PO+SF-1, PO+SF-2, and PO+SF-4 groups all showed a significant decrease in right ventricular systolic function (*). p <0.05,** p <0.01). This indicates that the extract of Soufeng Sanjie can significantly improve cardiac function damage in rats.

[0074] 3. Susceptibility test for atrial fibrillation in rats: Take the wind-dispersing and stagnation-removing extract group 3# from Example 3 as SF in PO+SF group to form PO+SF-3 group.

[0075] The day after the last gavage administration of PO+SF-3, the susceptibility to atrial fibrillation in rats of each group was assessed using the right jugular vein cannulation method. Rats were anesthetized with isoflurane and fixed on a control table. Needle electrodes were inserted subcutaneously into the limbs and connected to a biosignal acquisition and processing system to record surface electrocardiograms (ECGs). The right external jugular vein was isolated, and a pacing catheter with a stimulating electrode attached to its tip was inserted into the right atrium via the external jugular vein. Electrode position was confirmed by ECG waveform analysis. Single stimulation was applied with incrementally increasing voltage, and the minimum voltage value required for a stable atrial pacing wave on the ECG was observed as the pacing threshold. Subsequently, high-frequency burst stimulation was performed at twice the pacing threshold, repeated three times with a one-minute interval between each stimulation. Atrial fibrillation induction was recorded. The criteria for diagnosing atrial fibrillation were the appearance of rapid, irregular atrial fibrillation waves on the ECG, with absolutely irregular RR intervals. The NC and PO groups underwent simultaneous testing. Detailed experimental results are available in [link to relevant documentation]. Figure 2 .

[0076] Depend on Figure 2As shown in Figure A, when the PO+SF-3 group was used in the experiment, the probability of atrial fibrillation induced in the NC group was 30%, while the probability of atrial fibrillation induced in the PO group after surgery was 90%. After 21 days of administration of the drug, the atrial fibrillation induction rate in rats was significantly reduced to 70%. Figure B shows the duration of atrial fibrillation in each group of rats. The atrial fibrillation time in the PO group was 31.24s, while the average duration of atrial fibrillation in the PO+SF-3 group after administration was 5.76s, significantly reducing the atrial fibrillation time in rats (*). p <0.05). This indicates that the extract of Soufeng Sanjie can significantly reduce the susceptibility to atrial fibrillation in rats.

[0077] 4. Rats in the PO+SF, NC, and PO groups were fixed with 4% paraformaldehyde for 72 h and then dehydrated. The paraffin-impregnated tissues were embedded at 20℃ using an embedding machine. The paraffin blocks were cut into 4 μm thick slices using a paraffin sectioner, spread out onto glass slides, and baked in an oven. HE and Masson staining methods were used to observe the pathological changes in rat myocardial tissue. Specific experimental results are shown below. Figure 4 .Depend on Figure 4 As shown in Figure A, when the PO+SF-3 group was used in the experiment, the myocardial muscle fibers of the NC group rats were neatly and densely arranged, with very few blue collagen fibers, which were only distributed in small amounts around the blood vessels; the ventricular cavity morphology was regular, and the myocardial thickness was uniform. Figure B shows that the myocardial muscle fibers of the PO group rats were disordered and loosely arranged, with a significant increase in blue collagen fibers in the myocardial interstitium and around the blood vessels, and muscle fiber breakage and dissolution were visible in some areas; the ventricular cavity morphology was irregular. In Figure C, the degree of myocardial fibrosis in the PO+SF-3 group rats was reduced compared to the PO group, with fewer blue collagen fibers and partial recovery of muscle fiber arrangement; the ventricular cavity dilation was obvious, but the myocardial thickness was more uniform than that in the PO group.

[0078] In summary, the application of the wind-dispersing and nodule-resolving composition provided by this invention in the preparation of drugs for the prevention and treatment of stress overload cardiac injury represents the first discovery of the protective effect of this composition against stress overload cardiac injury, providing a new traditional Chinese medicine treatment option for the prevention and / or treatment of stress overload cardiac injury. Therefore, this invention effectively overcomes the various shortcomings of the prior art and has high industrial application value.

[0079] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.

Claims

1. Use of a wind-dispelling and nodule-resolving composition, extract, or preparation in the preparation of a medicament for the prevention and / or treatment of stress overload-induced cardiac injury.

2. Use of a wind-dispelling and nodule-resolving composition, extract, or preparation in the preparation of a chemical product for the prevention and / or treatment of stress overload-induced cardiac injury.

3. The use according to any one of claims 1-2, characterized in that, The wind-dispelling and nodule-dispersing composition comprises the following components by weight: 20-40 parts black soybean husk; 20-30 parts astragalus; 0.5-1.5 parts scorpion; and 0.5-1.5 parts centipede.

4. The use according to claim 3, characterized in that, The preparation of the wind-dispelling and nodule-resolving extract includes: soaking black soybean husks and astragalus root in water according to the proportion of the wind-dispelling and nodule-resolving composition, decocting, cooling and filtering, adding whole scorpion and centipede powder to the obtained filtrate, and mixing well to obtain the extract.

5. The use according to claim 4, characterized in that, The soaking time is 20-40 minutes.

6. The use according to claim 4, characterized in that, The decoction is performed 1-3 times; each decoction takes 1-2 hours.

7. The use according to claim 4, characterized in that, After each decoction, the mixture must be filtered by sieving through a sieve with a mesh size ≤ 0.5 mm.

8. The use according to claim 4, characterized in that, The powder of the whole scorpion and centipede is obtained by grinding and sieving, and the mesh size of the sieve is not less than 80 mesh.

9. The use according to claim 4, characterized in that, The wind-dispelling and nodule-resolving preparation comprises a therapeutically effective amount of the wind-dispelling and nodule-resolving composition, or a therapeutically effective amount of the wind-dispelling and nodule-resolving extract, and one or more conventional pharmaceutically acceptable excipients.

10. The use according to any one of claims 1-2, characterized in that, The prevention and / or treatment of stress overload-related cardiac injury is manifested in at least one of the following aspects: S1) Improves structural and functional damage to various chambers caused by pressure overload; S2) Improves the decrease in left ventricular ejection fraction caused by pressure overload; S3) Improves right ventricular function decline caused by pressure overload; S4) Improves the increased atrial fibrillation load caused by pressure overload; S5) Improves myocardial tissue inflammation caused by stress overload; S6) Improves myocardial fibrosis caused by stress overload.

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