Cream for supporting healthy energy, warming yang and dredging meridians

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations, and particularly discloses a healthy energy supporting, yang warming and meridian dredging paste which is technically characterized by being prepared from honey-fried ephedra, wine-processed cornus, safflower, red paeony root, stevia rebaudiana, prepared common monkshood daughter root, Chinese yam, kudzuvine root, prepared rhizome of rehmannia, platycodon grandiflorum, pollen typhae, ligusticum wallichii, angelica sinensis, radix achyranthis bidentatae, astragalus membranaceus, asarum, radix bupleuri, liquorice, peach kernel, lignum dalbergiae odoriferae and fructus aurantii according to a specific weight part ratio. According to the ointment formula, the theory of Zheng method of Yandezhi teaching professor and the experience of Radix Astragali-Radix Puerariae formula of Guizhongguang national medicine master are fused, a treatment system which warms yang, benefits qi, promotes blood circulation, removes blood stasis, strengthens the body resistance and dredges collaterals is established, and the ointment formula accurately aims at the core pathogenesis of yang deficiency and blood stasis type coronary heart disease angina pectoris and chronic heart failure. Clinical tests prove that the ointment is remarkably superior to conventional treatment (Plt; 0.05) in the aspects of improving traditional Chinese medicine syndromes and improving heart functions, and is good in safety; moreover, the preparation is an oral ointment, is moist and sweet in quality, is convenient to take for a long time, and has remarkable clinical application value and popularization prospect.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation technology, and more specifically, to a tonic plaster for strengthening the body's resistance, warming the yang, and promoting blood circulation. Background Technology

[0002] Coronary heart disease, angina pectoris, and chronic heart failure are common cardiovascular diseases in clinical practice, characterized by high incidence, high recurrence rate, and high disability rate, seriously threatening patients' quality of life. Traditional Chinese medicine believes that the pathogenesis of these diseases is complex, often related to insufficient heart yang, deficiency of qi and blood, cold stagnation and blood stasis, and phlegm and blood stasis. Especially for patients with a long disease course and weak constitution, "yang deficiency and blood stasis" is the core syndrome characteristic; that is, yang deficiency is the root cause, and blood stasis is the manifestation, with the two mutually reinforcing each other, forming a vicious cycle. Therefore, treatment should not only focus on promoting blood circulation and unblocking the meridians to treat the symptoms, but also on warming yang and strengthening the body's resistance to consolidate the root cause, in order to achieve a comprehensive cure.

[0003] Currently, various traditional Chinese medicine preparations are available on the market for the adjunctive treatment of angina pectoris and chronic heart failure, such as Danshen dripping pills, compound Danshen tablets, Shenmai injection, and Qili Qiangxin capsules. However, existing products on the market generally have the following defects and shortcomings, making it difficult to meet the clinical needs of long-term conditioning and individualized intervention for patients with "Yang deficiency and blood stasis type":

[0004] 1. The treatment theory is too simplistic and fails to grasp the essence of "Yang deficiency".

[0005] Most existing traditional Chinese medicine preparations focus on promoting blood circulation, removing blood stasis, clearing heat, and unblocking the meridians, while neglecting the crucial role of Yang deficiency in the pathogenesis of angina pectoris and chronic heart failure. For example, preparations containing ingredients such as Danshen and Sanqi have certain effects on promoting blood circulation and relieving pain, but they are not effective for symptoms such as depletion of heart Yang, Qi deficiency and fatigue, aversion to cold and cold limbs, and soreness of the waist and knees caused by Yang deficiency. In fact, due to the cold nature of the medicine, prolonged use may "damage Yang," which is not conducive to the long-term conditioning of patients with deficiency syndromes.

[0006] 2. The prescription combination lacks classical support and the compatibility structure is incomplete.

[0007] Some products use simplified medicinal ingredients, focusing only on a single therapeutic dimension (such as promoting blood circulation or invigorating qi), lacking the completeness and hierarchy of classic Chinese medicine formulas, and failing to reflect the principle of "principal, assistant, adjuvant, and guide" in prescription. This "lone wolf" approach to formulation makes it difficult to achieve the therapeutic goal of "treating both the symptoms and the root cause," resulting in short-lived efficacy, insufficient conditioning power, and failure to meet the Chinese medicine treatment concept of "strengthening the body's resistance and eliminating pathogenic factors" through two-way regulation.

[0008] 3. Poor dosage form design leads to poor adherence to long-term use for chronic diseases.

[0009] Most existing related drugs are in tablet, capsule, drop, or injection form. While these are convenient for mass production, they are not well-suited for the long-term use needs of the elderly. Tablets and capsules disintegrate and are absorbed slowly in the body, drop pills have a fast onset of action but a short duration of action, and injections are inconvenient to use and have low patient acceptance. Some preparations are bitter and cold in nature, making them difficult to swallow and affecting patient compliance. None of these dosage forms conform to the tonifying and regulating principles of the *Neijing* (Inner Canon of Medicine), which states that "treatment must seek the root cause of disease, and ointments should be used to nourish it."

[0010] 4. Lacks integration of renowned experts' experience and fails to reflect the concept of individualized conditioning.

[0011] Currently, there is a lack of systematic integration of the academic experience of renowned TCM masters (such as Professor Yan Dexin's "Hengfa" theory and Master Guo Ziguang's "Qi Ge Fang" experience) and its application in the production of specialized disease-specific herbal pastes that can be industrialized. Most similar products have failed to achieve breakthroughs in the dual approach of "treating disease + regulating the body," and cannot adequately meet the modern TCM development needs of "preventing disease," "maintaining health and preventing disease progression," and "continuing clinical rehabilitation and treatment."

[0012] 5. Lack of synergistic mechanism design, incomplete pharmacodynamic spectrum.

[0013] Most existing drugs tend to follow the principle of "no tonification if there is free flow" or "no free flow if there is tonification," failing to address the issue of synergistic and balanced efficacy in patients with both Yang deficiency and blood stasis. For patients with accompanying symptoms such as decreased cardiac function, insufficient circulatory power, and decreased peripheral perfusion, preparations that solely promote blood circulation or simply tonify Qi are unlikely to comprehensively improve the underlying symptoms, resulting in limited clinical efficacy.

[0014] In conclusion, developing a traditional Chinese medicine preparation that can both warm the body's yang and strengthen its resistance, promote blood circulation and unblock the meridians, and is suitable for long-term use, has significant clinical importance and market demand.

[0015] Therefore, this application proposes a tonic plaster for strengthening the body's resistance, warming the body's yang, and promoting blood circulation to solve the above problems. Summary of the Invention

[0016] The purpose of this invention is to provide a tonifying and invigorating plaster that warms the body and promotes blood circulation, thereby solving the problems of single treatment theory, incomplete formulation, poor dosage form adaptability, and lack of synergistic mechanism in the existing technology. It achieves the therapeutic effects of warming the body and invigorating qi, promoting blood circulation and unblocking collaterals, and tonifying the body and strengthening the body. It is especially suitable for patients with angina pectoris and chronic heart failure of coronary heart disease with yang deficiency and blood stasis.

[0017] The above-mentioned objective of the present invention is achieved as follows:

[0018] One aspect of the present invention provides a tonic plaster for strengthening the body, warming the yang, and promoting blood circulation, made from the following medicinal materials, in parts by weight:

[0019] Honey-processed ephedra 6 parts; wine-processed cornus 16 parts; safflower 4 parts; red peony root 10 parts; stevia 2 parts; lightly processed aconite root 12 parts; yam 20 parts; kudzu root 16 parts; prepared rehmannia root 16 parts; platycodon root 4 parts; cattail pollen 10 parts; chuanxiong rhizome 10 parts; angelica root 10 parts; achyranthes root 10 parts; astragalus root 24 parts; asarum root 2 parts; bupleurum root 4 parts; licorice root 6 parts; peach kernel 8 parts; dalbergia odorifera 4 parts; bitter orange peel 4 parts.

[0020] Furthermore, the dosage form of the Fuzheng Gubenwen Yangtongmao ointment is an oral ointment.

[0021] Another aspect of the present invention provides a method for preparing a tonic plaster that strengthens the body, warms the yang, and unblocks the meridians, comprising the following steps:

[0022] S1. Preparation and soaking: Select Chinese medicinal herbs according to the proportion, ensuring they are free from mold and insects. After cleaning, pack them into non-woven bags, seal them, and soak them in water for 12-20 hours.

[0023] S2. Decoction and Concentration: The decoction is carried out multiple times using a steam decoction machine, with the decoction temperature controlled at 100-105 degrees Celsius. The first decoction time is 3.5 hours, the second decoction time is 2.5 hours, and the third decoction time is 1.5 hours. The decoctions are combined and concentrated to the predetermined concentration using a high-pressure concentrator.

[0024] S3. Concentration and Preparation: After the concentrate has settled, the supernatant is collected and prepared as needed, and excipients are added for further preparation.

[0025] S4. Dispensing and Cooling: Dispense the ointment into clean packaging containers according to the dosage standard, cool to room temperature or below 20°C and seal.

[0026] S5. Quality Control and Packaging: Each batch of herbal paste undergoes three layers of quality inspection before being packaged, coded, and stored.

[0027] Furthermore, the frying process described in step S2 is carried out using a KSP-400 steaming and frying machine.

[0028] Furthermore, the concentration described in step S2 is carried out using a high-pressure concentrator.

[0029] Furthermore, the clean packaging container mentioned in step S4 is an aluminum foil bag or a glass bottle.

[0030] Furthermore, the three-layer quality inspection mentioned in step S5 involves 80-day, 100-day, and 120-day stability sampling inspections, with storage humidity conditions of 50%-70%.

[0031] Another aspect of the present invention provides the application of Fuzheng Gubenwen Yangtongmai ointment in the preparation of a drug for treating angina pectoris or chronic heart failure of coronary heart disease with yang deficiency and blood stasis.

[0032] Compared with the prior art, the present invention has the following beneficial effects:

[0033] 1. This invention takes Professor Yan Dexin's "Balance Method" academic system, which states that "with a bit of Yang Qi, there is a bit of vitality" and "Yang deficiency is the root cause, and blood stasis is the manifestation," as its theoretical core. It integrates the clinical experience of Master Guo Ziguang's "Astragalus and Kudzu Formula" and innovatively combines the four methods of warming Yang, tonifying Qi, activating blood, and unblocking collaterals. It establishes a holistic treatment system that emphasizes "strengthening the body's resistance, warming Yang and unblocking the meridians, tonifying Qi and activating blood, and regulating Qi and relieving pain." This theoretical model accurately corresponds to the core pathogenesis of stable angina pectoris and chronic heart failure of the "Yang deficiency and blood stasis type," overcoming the theoretical defects of existing products that only focus on activating blood or tonifying Qi and ignore the essence of Yang deficiency.

[0034] 2. This invention's formula consists of 20 traditional Chinese medicines, cleverly integrating classic formulas such as Ephedra, Asarum, and Aconite Decoction, Peach Blossom and Four-Substance Decoction, and Blood-Activating and Stasis-Removing Decoction, forming a synergistic treatment pattern of warming yang, tonifying qi, activating blood, and unblocking collaterals. Specifically: Prepared Aconite Root, Asarum, and Honey-processed Ephedra warm yang and dispel cold to support heart yang; Astragalus, Dioscorea, Rehmannia, and Cornus Fruit tonify qi and nourish yin to strengthen the foundation; Peach Kernel, Safflower, Angelica, Ligusticum, Red Peony Root, Typha Pollen, and Dalbergia Indicum activate blood and remove stasis to unblock the meridians; Bupleurum, Aurantium, Platycodon, and Achyranthes Root regulate qi to smooth the pivot. The combined use of these herbs emphasizes both regulating the constitution and alleviating clinical symptoms, achieving the treatment goal of "tonifying without stagnation and unblocking without harm," thus overcoming the synergistic defects of existing products that either "do not tonify when unblocking" or "do not unblock when tonifying."

[0035] 3. The product of this invention is a thick, dark brown paste, smooth and moist in texture, with a rich medicinal aroma and a sweet taste. It is easily absorbed under the tongue and released slowly, making it suitable for long-term use and conditioning of the body. As an important carrier of "preventive treatment" in Traditional Chinese Medicine, medicinal pastes have the unique advantages of being "nourishing without being greasy, effective with prolonged use, and gentle and harmonizing," making them particularly suitable for medium- to long-term conditioning and treatment of people with weak constitutions and chronic diseases. Compared with fast-acting dosage forms such as tablets, capsules, and pills, the medicinal paste of this invention is more in line with the refined theory of "medicinal paste is essence" in the *Neijing* (Inner Canon of Medicine), overcoming the shortcomings of existing preparations that are quickly absorbed but have short-lasting effects and are not suitable for long-term use by people with weak constitutions.

[0036] 4. The product of this invention has completed a randomized controlled clinical trial involving 60 patients with chronic heart failure of the Yang deficiency and blood stasis type. The results showed that the treatment group was significantly better than the control group in terms of improvement of TCM syndrome, decrease in heart failure score, and improvement in cardiac function classification (P<0.05). No serious adverse reactions occurred during the treatment, demonstrating good safety and tolerability.

[0037] 5. This invention systematically integrates Professor Yan Dexin's "Hengfa" academic system and Guo Ziguang's clinical experience with "Qi Ge Fang," transforming the academic thoughts of renowned experts into industrially viable specialized disease-specific herbal paste products. At the "disease treatment" level, it can significantly improve patients' cardiac function and clinical symptoms; at the "body conditioning" level, it can systematically regulate Yang deficiency and blood stasis constitution, aligning with the modern TCM development needs of "preventive treatment," "disease prevention and control," and "continuing clinical rehabilitation treatment." Attached Figure Description

[0038] Figure 1 The bar chart for the functional enrichment analysis of the core active ingredient GO in the Fuzheng Gubenwen Yangtongmai ointment in this embodiment of the invention (showing the enrichment results in three dimensions: biological process, cellular component, and molecular function, among which the related items such as RNA polymerase II transcriptional regulation, DNA-binding transcription factor activity, DNase I hypersensitivity reaction, nuclear RNA polymerase binding, and ubiquitin-like protein binding are significantly enriched).

[0039] Figure 2 This is an example of an interaction network between YQWYTM compounds, herbal sources, and predicted disease-related targets in this invention (11 green squares represent the constituent herbs of YQWYTM; orange, cyan, and magenta circles represent the main active compounds of each herb; red triangles represent common compounds appearing in multiple herbs; the 263 yellow rectangles in the center represent predicted therapeutic targets identified from the active ingredients; the edges represent the interactions between herbs and compounds, as well as the interactions between compounds and their corresponding targets).

[0040] Figure 3 The composite disease target network in this embodiment of the invention (after removing duplicates from multiple disease databases, a total of 9,050 coronary heart disease-related targets were identified; these targets were compared with YQWY™ compound targets using Venn diagrams, revealing 234 shared targets; to elucidate the complex relationship between bioactive components and disease-related targets, this composite disease target network was established; then, a protein-protein interaction (PPI) network containing 55 nodes and 296 edges was constructed based on the shared targets; in this network, node size and opacity are proportional to node degree, indicating the likelihood of becoming a central target; using a "median-based iterative filtering" strategy, through three rounds of optimization of the topology threshold (Degree > 8, BC > 4.59, CC > 0.67), six key genes were finally identified: TP53, AKT1, MYC, MAPK1, MAPK3, and ESR1).

[0041] Figure 4In this embodiment of the invention, three machine learning algorithms—LASSO, SVM-RFE, and Random Forest (RF)—were used to screen key genes in the training dataset and optimize target priority (a: LASSO reduced the original 6 genes to 5; b: SVM-RFE identified 5 optimal genes with a peak RMSE of 0.77 and a minimum RMSE of 0.23; c: RF analysis also selected 5 genes based on feature importance ranking; d: To enhance robustness and reduce method-specific bias, three complementary feature selection algorithms (LASSO, SVM-RFE, and RF) were applied. Considering interpretability and the feasibility of downstream validation, the top-ranked features (top 3) of each method were retained (ranked by coefficient size in LASSO, by feature elimination in SVM-RFE, and by variable importance in RF), and the intersection was defined as the core genes. The intersection of these three algorithms consistently identified two core genes: AKT1 and MYC, which were used for subsequent structural validation).

[0042] Figure 5 This is a thermal energy diagram of the molecular docking binding energy of the ingredients in the medicinal paste in this embodiment of the invention;

[0043] Figure 6 In this embodiment of the invention, network pharmacology was used to identify five basic active ingredients of YQWYTM: sitosterol, stigmasterol, kaempferol, luteolin, and quercetin (these compounds were molecularly docked with the 4GV1 protein encoded by AKT1; this analysis aimed to determine the key role of these compounds in the treatment of coronary heart disease; subsequently, the docking results of the protein and ligands were examined separately, and the Autodock results were summarized; it is generally believed that the lower the intermolecular binding energy, the stronger the affinity; typically, a binding energy below -5 kJ / mol indicates a strong binding between the ligand and the receptor; the results show that these five small molecules have good binding affinity to the protein encoded by AKT1; notably, sterols exhibited the most favorable binding energy, indicating a particularly strong interaction with AKT1; furthermore, the interactions between all ligand-macromolecule complexes were mediated by hydrogen bonds, thus ensuring the stability of these bindings). Detailed Implementation

[0044] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0045] The implementation of the present invention will be described in detail below with reference to specific embodiments.

[0046] Example 1: Preparation of a tonic plaster for strengthening the body, warming the yang, and promoting blood circulation

[0047] 1. Prescription Composition

[0048] Honey-processed ephedra 6g, wine-processed cornus officinalis 16g, safflower 4g, red peony root 10g, stevia 2g, light-processed aconite root 12g, yam 20g, kudzu root 16g, prepared rehmannia root 16g, platycodon root 4g, cattail pollen 10g, chuanxiong rhizome 10g, angelica root 10g, achyranthes root 10g, astragalus root 24g, asarum root 2g, bupleurum root 4g, licorice root 6g, peach kernel 8g, sandalwood 4g, and immature bitter orange peel 4g.

[0049] 2. Preparation process

[0050] (1) Preparation and soaking: Select the above-mentioned Chinese medicinal materials that meet the quality standards of the Chinese Pharmacopoeia, ensuring that they are free from mold and insects. After professional cleaning, pack them into non-woven bags and seal them. Place the wrapped medicinal materials in an extraction tank, add clean water, and the water level should be enough to cover the surface of the medicinal materials. Soak for 15 hours to allow the medicinal materials to fully absorb water and expand, ensuring that the effective components are fully extracted during the decoction process.

[0051] (2) Decoction and concentration: A KSP-400 steam decoction machine was used for decoction. The decoction temperature was set at 103℃, the first decoction time was 3.5 hours, and the decoction was filtered. The second decoction was decocted for 2.5 hours after adding water, and the decoction was filtered. The third decoction was decocted for 1.5 hours after adding water, and the decoction was filtered. The three decoctions were combined, filtered through a 100-mesh sieve to remove the dregs, and concentrated to a clear paste with a relative density of 1.25-1.30 (measured at 60℃) using a high-pressure concentrator.

[0052] (3) Concentration and preparation of the paste: Let the concentrated liquid stand for 24 hours to settle, take the supernatant and continue to concentrate. Use the traditional "hanging flag" or "dropping water forms beads" method to determine the endpoint of the concentration, so that the medicinal properties are concentrated and the texture is uniform. According to the prescription, an appropriate amount of excipients can be added to improve palatability, stability and formability. Stir thoroughly to mix well.

[0053] (4) Packaging and cooling: The obtained ointment is packaged into aluminum foil bags or glass bottles according to the standard of 15g per bag or 200g per bottle, sealed and placed in a cooling room, cooled to room temperature (below 20℃) and then stored.

[0054] (5) Quality control and packaging: Each batch of herbal paste undergoes three layers of quality inspection (80-day, 100-day, and 120-day stability sampling inspections) to test indicators such as appearance, moisture, microbial limits, and effective ingredient content. After passing the inspection, the paste is packaged, coded, and stored in an environment with 50%-70% humidity.

[0055] Example 2: Clinical study of Fuzheng Gubenwen Yangtongmai ointment in the treatment of chronic heart failure of Yang deficiency and blood stasis type.

[0056] 1. Research Subjects

[0057] Sixty patients with chronic heart failure of the Yang deficiency and blood stasis type who met the diagnostic criteria were included. They were randomly divided into a treatment group and a control group, with 30 patients in each group. There were no statistically significant differences between the two groups in terms of baseline characteristics such as gender, age, disease duration, underlying diseases, and cardiac function classification (P>0.05), indicating comparability.

[0058] 2. Diagnostic criteria

[0059] (1) Western medicine diagnostic criteria: The diagnostic criteria for chronic heart failure in the Chinese Guidelines for the Diagnosis and Treatment of Heart Failure are referred to, and the heart function classification adopts the New York Heart Association (NYHA) heart function classification criteria.

[0060] (2) Traditional Chinese Medicine diagnostic criteria: Refer to the diagnostic criteria for "Yang deficiency and blood stasis syndrome" in the "Guiding Principles for Clinical Research of New Chinese Medicine". Main symptoms: palpitations, shortness of breath, aversion to cold and cold limbs, chest and rib pain; Secondary symptoms: fatigue, soreness and weakness of the waist and knees, facial and limb edema, cyanosis of lips and nails; Tongue and pulse: dark purple tongue or with ecchymosis, white and slippery coating, deep and thready or hesitant pulse.

[0061] 3. Treatment methods

[0062] Control group: Received routine Western medicine treatment, including diuretics, angiotensin-converting enzyme inhibitors (ACEIs) / angiotensin II receptor antagonists (ARBs), beta-blockers, digitalis preparations, etc., with the medication regimen adjusted according to the patient's specific condition.

[0063] Treatment group: In addition to the routine Western medicine treatment of the control group, the treatment group also took the Fuzheng Gubenwen Yangtongmao ointment prepared in Example 1 of this invention, 15g once a day, dissolved in warm water, for 4 consecutive weeks as one course of treatment.

[0064] 4. Observation Indicators

[0065] (1) Traditional Chinese Medicine (TCM) syndrome score: Referring to the TCM syndrome scoring criteria in the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs", the main symptoms such as palpitations, shortness of breath, aversion to cold and cold limbs, chest and rib pain, fatigue, and soreness of the waist and knees were scored. Evaluation was conducted once before and once after treatment. Efficacy judgment criteria: Marked effect: TCM syndrome score decreased by ≥70%; Effective: TCM syndrome score decreased by ≥30% and <70%; Ineffective: TCM syndrome score decreased by <30%; Total effective rate = (Marked effect + Effective) / Total number of cases × 100%.

[0066] (2) Cardiac function classification: The NYHA cardiac function classification standard was used to evaluate the improvement of cardiac function before and after treatment.

[0067] (3) Plasma brain natriuretic peptide (BNP) level: Fasting venous blood was collected before and after treatment to detect plasma BNP level.

[0068] (4) Safety indicators: Blood routine, urine routine, liver and kidney function, electrocardiogram, etc. are tested before and after treatment, and adverse reactions that occur during treatment are recorded.

[0069] 5. Research Results

[0070] (1) Comparison of TCM syndromes and their therapeutic effects

[0071] After 4 weeks of treatment, the total effective rate of TCM symptoms in the treatment group was significantly higher than that in the control group, and the difference between the two groups was statistically significant (P<0.05). This indicates that the herbal paste of the present invention can significantly improve the TCM clinical symptoms of patients with chronic heart failure of Yang deficiency and blood stasis type.

[0072] (2) Comparison of improvement in cardiac function

[0073] The improvement in cardiac function was significantly better in the treatment group than in the control group (P<0.05). This indicates that the herbal paste of the present invention has good efficacy in enhancing heart yang and improving blood pumping function.

[0074] (3) Comparison of plasma BNP levels

[0075] Plasma BNP levels in both groups decreased significantly after treatment compared to pre-treatment levels (P<0.05). The decrease in BNP levels was more stable in the treatment group, reflecting that this product has a certain regulatory effect on the neuroendocrine system.

[0076] (4) Safety evaluation

[0077] No serious adverse reactions occurred in either group of patients during the treatment. No significant abnormalities were observed in the blood routine, urine routine, liver and kidney function, and electrocardiogram indicators of the treatment group, indicating that the herbal paste of this invention has good safety and tolerability.

[0078] The research results of this embodiment of the invention show that Fuzheng Guben Wenyang Tongmai Ointment, as an innovative formula guided by the TCM theory of "supporting yang and removing blood stasis", can significantly improve the clinical symptoms and cardiac function of patients with chronic heart failure of yang deficiency and blood stasis type when used in combination with conventional treatment, and has good safety.

[0079] Example 3: Network pharmacology and bioinformatics analysis of Fuzheng Gubenwen Yangtongmai plaster for treating coronary heart disease

[0080] The medicinal herbs contained in this invention's herbal paste have been studied using modern network pharmacology and bioinformatics methods. Preliminary screening has identified their core active ingredients as including sitosterol, stigmasterol, luteolin, kaempferol, and quercetin. The herbal paste of this invention is classified according to these five components, and the specific implementation is as follows:

[0081] 1. Screening of active ingredients: Using network pharmacology and bioinformatics methods, the active ingredients of the traditional Chinese medicines contained in the Fuzheng Guben Wenyang Tongmai Ointment of the present invention were analyzed. Through the research of modern network pharmacology and bioinformatics methods, the core active ingredients and their sources of various traditional Chinese medicines contained in the ointment of the present invention were initially screened as follows:

[0082] Element Chinese medicine name Kaempferol Astragalus; Safflower; Cornus officinalis; Bupleurum; Typha pollen sitosterol Kudzu root; Rehmannia root; Huangshan (a type of medicinal herb); Angelica sinensis; Platycodon grandiflorus Stigmasterol Angelica sinensis; Rehmannia glutinosa Quercetin Astragalus; Licorice; Safflower; Cornus officinalis; Bupleurum; Typhae pollen; Platycodon grandiflorus Lignin Safflower; Platycodon grandiflorus; Dalbergia odorifera; Paeonia lactiflora

[0083] The above five core active ingredients (kaempferol, sitosterol, stigmasterol, quercetin, luteolin) are widely distributed, indicating that the ointment of the present invention has the basis for the synergistic effect of multiple components.

[0084] 2. Target prediction and GO functional enrichment analysis

[0085] The potential targets of the above components were predicted by network pharmacology, and GO functional enrichment analysis was performed. As Figure 1 shown, the results of GO functional enrichment analysis cover three dimensions: biological process, cellular component, and molecular function. Among them, in this example, gene ontology (GO) enrichment analysis was performed on the top 10 biological processes, cell components, and molecular functions before enrichment. The results showed that the candidate target genes were mainly enriched in biological processes, such as "response to external stimuli", "response to lipopolysaccharide", and "response to molecules of bacterial origin". These results indicate that the Fuzheng Guben Wenyang Tongmai Ointment may play a therapeutic role by regulating the cellular defense response of CHD. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the potential mechanism of the Fuzheng Guben Wenyang Tongmai Ointment in treating coronary heart disease was further clarified. The results showed that the top 10 significantly enriched signaling pathways included "lipid and atherosclerosis", "fluid shear stress and atherosclerosis", and "AGE-RAGE signaling pathway".

[0086] 4. Mechanism of action: The above active substances may play a role in treating coronary heart disease by regulating the PI3K / AKT1 signal axis of AKT1, mediating the restoration of endothelial cell function, anti-inflammatory and anti-apoptotic effects, and the formation of stable plaques.

[0087] 5. Mechanism correlation analysis: In the heart diseases of yang deficiency and blood stasis type to be treated in the present invention, "insufficient heart yang" can establish a corresponding relationship with the myocardial cell energy metabolism disorder described in modern medicine. Yang qi performs the functions of warming and promoting in the human body, and its role is similar to the energy generated by the hydrolysis of mitochondrial ATP in the body. Therefore, the syndrome of heart yang deficiency in traditional Chinese medicine syndrome differentiation can be analogized to the state of myocardial cell mitochondrial dysfunction.

[0088] Modern research indicates that inflammation and mitochondrial dysfunction are crucial mechanisms underlying the persistent progression of cardiomyocyte damage. Increased levels of inflammatory mediators such as TNF-α, IL-1β, and IL-6 can be observed in the myocardium, accompanied by abnormal activation of inflammatory signaling pathways such as NF-κB and NLRP3 inflammasomes. These inflammatory stimuli promote the production of large amounts of reactive oxygen species and exacerbate calcium overload, while directly impairing the function of the mitochondrial electron transport chain, leading to reduced ATP synthesis, decreased mitochondrial membrane potential, and impaired oxidative phosphorylation. As mitochondrial damage worsens, mitochondrial ROS, oxidized mitochondrial DNA, and other damage-related molecules are further leaked, which in turn amplifies the inflammatory cascade, creating a vicious cycle where inflammation and mitochondrial damage mutually reinforce each other. Simultaneously, persistent inflammation can induce excessive mitochondrial fission, inhibited fusion, and impaired mitophagy clearance, leading to the continuous accumulation of dysfunctional mitochondria. This triggers abnormal mPTP opening, cytochrome c release, and programmed cell damage processes such as apoptosis, necrosis, or pyroptosis, ultimately resulting in decreased cardiomyocyte activity, impaired contractile function, and progressive myocardial remodeling.

[0089] If we take "yang qi" as the foundation for the body's propulsion and warmth, then in the context of modern biology, it can be compared to the effective energy supply and metabolic homeostasis required to maintain myocardial function. Therefore, "heart yang deficiency" not only means low function, but also points to the fragility of the energy system and the decline in its ability to resist damage.

[0090] Based on this mechanism framework, the spleen-strengthening, qi-tonifying, yang-warming and righteous-strengthening herbs used in this invention (such as Astragalus membranaceus, Aconitum carmichaelii, Dioscorea opposita, Asarum heterotropoides, etc.) have been suggested by modern pharmacological studies to have potential for mitochondrial protection and metabolic remodeling: their effects can be manifested in improving myocardial ATP synthesis efficiency, improving mitochondrial membrane potential, reducing ROS and lipid peroxidation levels, and regulating mitochondrial autophagy and kinetic balance, thereby enhancing the survival and contractile function of myocardial cells under ischemic / oxidative stress.

[0091] Analysis of the mechanism of "promoting blood circulation and clearing blood vessels": In the context of modern medicine, "promoting blood circulation and clearing blood vessels" can be interpreted as a comprehensive intervention on the continuous pathological chain of hemodynamics-thrombosis-plaque stability: by improving blood rheology (reducing blood viscosity, improving erythrocyte deformability and microcirculation perfusion), regulating vascular endothelial function (promoting NO production, reducing endothelial adhesion molecule expression), and inhibiting excessive platelet activation and coagulation-fibrinolysis imbalance, the risk of thrombosis reformation can be reduced in patients with coronary heart disease and after PCI. Furthermore, by reducing local inflammatory response and oxidative stress and improving coronary perfusion, the stability of the plaque fibrous cap can be promoted and plaque vulnerability can be reduced.

[0092] 6. The network pharmacology results of this invention show that AKT1 is a key target, with related signals mainly enriched in the PI3K / AKT pathway and involved in pathways such as lipid and atherosclerosis. Under pathological conditions such as myocardial ischemia, hypoxia, persistent inflammation, and atherosclerosis, inflammatory mediators such as TNF-α, IL-1β, and IL-6, as well as oxidative stress responses, can be continuously amplified, thereby damaging the mitochondrial electron transport chain function, leading to reduced ATP production, decreased mitochondrial membrane potential, abnormal accumulation of reactive oxygen species, and calcium homeostasis imbalance. Simultaneously, the mitochondrial ROS and related damage signals released after mitochondrial damage can further amplify the inflammatory cascade, forming a vicious cycle of mutually reinforcing inflammation and mitochondrial damage. AKT1, as an important node in the PI3K / AKT pathway, can participate in regulating cell survival, anti-apoptosis, anti-oxidative stress, and mitochondrial homeostasis maintenance; when this pathway is dysfunctional, it is often accompanied by excessive mitochondrial fission, insufficient autophagy clearance, abnormal opening of mPTPs, and increased cardiomyocyte apoptosis or necrosis, ultimately leading to decreased myocardial contractility and progression of myocardial remodeling. Therefore, this invention suggests that the Fuzheng Guben Wenyang Tongmai ointment may exert a cardioprotective effect by acting on AKT1 and regulating PI3K / AKT and anti-atherosclerosis-related pathways, reducing inflammatory response and oxidative stress, and improving mitochondrial dysfunction.

[0093] In summary, the formula of this invention uses peach kernel, safflower, red peony root, angelica, and chuanxiong as the core ingredients for promoting blood circulation and removing blood stasis, working together to address the "blood stasis-microcirculation disorder-ischemia" pathway. It is combined with platycodon and immature bitter orange to regulate qi, relieve chest tightness and pain, and improve hemodynamic blockage, while also enhancing the efficacy of the medicine in the chest. Dalbergia odorifera, with its pungent and dispersing properties, unblocks the meridians and relieves pain, improving coronary blood supply and alleviating ischemic pain. Achyranthes bidentata effectively guides blood downwards and unblocks blood vessels, synergistically improving peripheral circulation and blood stasis. Pueraria lobata primarily dilates blood vessels, improves endothelial response and coronary perfusion, forming a multi-pathway synergy of "regulating qi to promote blood circulation, unblocking the meridians to unblock the vessels, and removing blood stasis to stabilize plaques," thereby achieving a systematic intervention on coronary ischemia, thrombotic tendency, and plaque progression.

[0094] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A tonic plaster for strengthening the body, warming yang, and promoting blood circulation, characterized in that... Made from the following medicinal materials, by weight: Honey-processed ephedra 6 parts; wine-processed cornus officinalis 16 parts; safflower 4 parts; red peony root 10 parts; stevia 2 parts; lightly processed aconite root 12 parts; yam 20 parts; Kudzu root 16 parts; Rehmannia root 16 parts; Platycodon root 4 parts; 10 parts of Typha pollen; 10 parts of Ligusticum chuanxiong; 10 parts of Angelica sinensis; 10 parts of Achyranthes bidentata; 24 parts of Astragalus membranaceus; Asarum 2 parts; Bupleurum 4 parts; Licorice 6 parts; Peach kernel 8 parts; Dalbergia odorifera 4 parts; Aurantium 4 parts.

2. The tonic plaster for strengthening the body, warming yang, and promoting blood circulation according to claim 1, characterized in that, The dosage form of the Fuzheng Gubenwen Yangtongmao paste is an oral paste.

3. The preparation method of the tonic plaster for strengthening the body, warming the yang, and promoting blood circulation according to claim 1 or 2, characterized in that, Includes the following steps: S1. Preparation and soaking: Select Chinese medicinal herbs according to the proportion, ensuring they are free from mold and insects. After cleaning, pack them into non-woven bags, seal them, and soak them in water for 12-20 hours. S2. Decoction and Concentration: The decoction is carried out multiple times using a steam decoction machine, with the decoction temperature controlled at 100-105 degrees Celsius. The first decoction time is 3.5 hours, the second decoction time is 2.5 hours, and the third decoction time is 1.5 hours. The decoctions are combined and concentrated to the predetermined concentration using a high-pressure concentrator. S3. Concentration and Preparation: After the concentrate has settled, the supernatant is collected and prepared as needed, and excipients are added as needed. S4. Dispensing and Cooling: Dispense the ointment into clean packaging containers according to the dosage standard, cool to room temperature or below 20°C and seal. S5. Quality Control and Packaging: Each batch of herbal paste undergoes three layers of quality inspection before being packaged, coded, and stored.

4. The preparation method according to claim 3, characterized in that, The frying process described in step S2 is carried out using a KSP-400 steaming and frying machine.

5. The preparation method according to claim 3, characterized in that, The concentration described in step S2 is carried out using a high-pressure concentrator.

6. The preparation method according to claim 3, characterized in that, The clean packaging container mentioned in step S4 is an aluminum foil bag or a glass bottle.

7. The preparation method according to claim 3, characterized in that, The three-layer quality inspection mentioned in step S5 is a stability sampling inspection at 80 days, 100 days, and 120 days, with storage humidity conditions of 50%-70%.

8. The use of the Fuzheng Gubenwen Yangtongmai ointment according to claim 1 or 2 in the preparation of a drug for treating angina pectoris or chronic heart failure of coronary heart disease with Yang deficiency and blood stasis.

Images