Traditional Chinese medicine composition for treating hypertensive heart failure, traditional Chinese medicine preparation and application thereof

Abstract

The invention provides a traditional Chinese medicine composition for treating hypertensive heart failure, a traditional Chinese medicine preparation and application thereof. The traditional Chinese medicine composition is prepared from, by weight, 9-30 parts of radix astragali, 10-15 parts of radix salviae miltiorrhizae, 9-30 parts of herba leonuri, 3-10 parts of rhizoma gastrodiae, 6-10 parts of cortex eucommiae, 9-15 parts of herba taxilli, 3-10 parts of radix scutellariae and 9-30 parts of raw oyster shells. Meanwhile, the invention further discloses a traditional Chinese medicine preparation. According to the traditional Chinese medicine theory and the precise syndrome differentiation and treatment theory, the traditional Chinese medicine composition and the traditional Chinese medicine preparation have the effects of tonifying qi, activating blood circulation and tonifying the liver and kidney, can effectively treat qi deficiency, blood stasis and liver and kidney deficiency syndromes of hypertension heart failure, and are particularly suitable for patients with left ventricular ejection fraction retention.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicines, and specifically comprises a traditional Chinese medicine composition for treating hypertension and heart failure, a traditional Chinese medicine preparation and application thereof. Background Art

[0002] Hypertension is a common cardiovascular disease. Long-term poor control of hypertension leads to increased cardiac burden and changes in cardiac structure, organization and function. Left ventricular hypertrophy or congestive heart failure caused by hypertension’s damage to the target organ heart is called hypertensive heart disease. Hypertensive heart failure is a serious complication of hypertension in the terminal stage. Its pathological mechanism involves left ventricular remodeling, myocardial fibrosis and cardiac decompensation caused by long-term high blood pressure. The lifetime risk of heart failure in hypertensive patients is twice that of patients with normal blood pressure. Hypertensive heart failure increases the rate of re-hospitalization, all-cause mortality and cardiovascular mortality. Therefore, the management and treatment of hypertensive heart failure are of great significance to the long-term survival and prognosis of patients.

[0003] At present, the treatment of hypertensive heart failure is mainly based on conventional Western medicine. It is recommended to carry out the best treatment according to the hypertension guidelines. The first choice of antihypertensive drugs is angiotensin receptor neprilysin inhibitors, and angiotensin converting enzyme inhibitors / angiotensin II receptor antagonists and beta-blockers can be used. However, some patients have problems such as poor drug tolerance, obvious side effects or limited efficacy, and current evidence cannot show that the above drugs can improve the prognosis of hypertensive heart failure.

[0004] Traditional Chinese medicine has unique advantages in the treatment of cardiovascular diseases. Evidence shows that Chinese herbal compound can significantly improve cardiac function and quality of life in patients with hypertensive heart failure. Its multi-target and multi-pathway mechanism of action provides new ideas for the comprehensive intervention of hypertensive heart failure. In clinical practice, classic prescriptions such as Zhenwu Decoction, Shengmai Drink, and Xuefu Zhuyu Decoction are widely used to improve cardiac function and alleviate symptoms, but traditional compound prescriptions have limitations such as complex ingredients, unknown effective material basis, and poor quality controllability. With the deepening of modern pharmacology research and the requirements for precise intervention in specific pathological links of hypertensive heart failure, selecting safer and more effective Chinese herbal prescriptions for clinical practice has become the core work at present. Summary of the invention

[0005] In view of the above problems existing in the prior art, the first object of the present invention is to provide a Chinese medicine composition for treating hypertensive heart failure.

[0006] The second object of the present invention is to provide a Chinese medicine preparation for treating hypertensive heart failure.

[0007] The third object of the present invention is to provide a use of the above-mentioned Chinese medicine composition or the above-mentioned Chinese medicine preparation in the preparation of a drug for treating hypertension and heart failure.

[0008] To achieve the above first object, the technical solution adopted by the present invention includes:

[0009] The present invention discloses a Chinese medicine composition for treating hypertension and heart failure. The Chinese medicine composition comprises the following raw materials in parts by weight:

[0010] 9-30 parts of Astragalus, 10-15 parts of Salvia miltiorrhiza, 9-30 parts of Leonurus japonicus, 3-10 parts of Gastrodia elata, 6-10 parts of Eucommia ulmoides, 9-15 parts of Morus alba, 3-10 parts of Scutellaria baicalensis, and 9-30 parts of raw oyster.

[0011] Based on the applicant's many years of clinical diagnosis and treatment experience, it is found that hypertensive heart failure belongs to qi deficiency and blood stasis, liver and kidney deficiency syndrome, which is caused by heart qi deficiency, heart pulse stasis, liver and kidney yin deficiency, and liver yang disturbance. Deficiency of the body, excessive fatigue, internal injury and seven emotions, etc., make qi and blood yin and yang deficiency, viscera dysfunction, and long-term illness to the heart, liver, and kidney, leading to heart qi deficiency and liver and kidney yin deficiency. "Shou Shi Bao Yuan·Blood Qi Theory" says: "Qi is the leader of blood. When qi moves, blood moves." If the heart qi is weak, the qi and blood will be weak, the blood will move slowly or even stagnate, causing the blood vessels of the heart to run poorly. Liver and kidney yin deficiency, unable to control yang, then liver yang disturbance. It is appropriate to invigorate qi and activate blood circulation, and nourish the liver and kidney. According to the theoretical system of TCM syndrome differentiation and the principle of monarch, minister, assistant and envoy compatibility of Chinese medicine, the Chinese medicine composition provided by the present invention contains eight Chinese medicinal materials including astragalus, salvia miltiorrhiza, motherwort, gastrodia, eucommia, mistletoe, scutellaria and raw oyster. Astragalus is the main drug, sweet in nature and slightly warm, and belongs to the lung and spleen meridians. It has the effects of replenishing qi and raising yang, consolidating the exterior and stopping sweating, promoting diuresis and reducing swelling, promoting fluid and nourishing blood, relieving stagnation and relieving arthralgia, expelling toxins and pus, and healing sores and promoting tissue regeneration. It has the effect of stimulating the circulation of qi and blood. Salvia miltiorrhiza, Leonurus japonicus, Gastrodia elata, Eucommia ulmoides, and Viscum album are the assistant drugs. Among them, liver yang disturbs the mind, and there will be heat symptoms such as restlessness. Salvia miltiorrhiza and Leonurus japonicus are cold in nature. Salvia miltiorrhiza can cool blood, relieve restlessness and calm the mind. Leonurus japonicus can clear away heat and detoxify. Salvia miltiorrhiza and Leonurus japonicus are used together to enhance the effect of promoting blood circulation and removing blood stasis. Gastrodia elata suppresses liver yang and treats the symptoms. Eucommia ulmoides and Viscum album nourish the liver and kidney to treat the root cause. They treat both the symptoms and the root cause, and nourish the liver and kidney to suppress liver yang. Scutellaria baicalensis is cold in nature, and it is used with Scutellaria baicalensis to enhance the heat-clearing effect of Salvia miltiorrhiza and Leonurus japonicus. Oyster can enhance the liver-soothing effect of Gastrodia elata, and oyster is a stone-like drug that can calm the mind. The whole formula has the functions of invigorating Qi, activating blood circulation, and nourishing the liver and kidneys.

[0012] Furthermore, the following raw materials are included in parts by weight:

[0013] 15-30 parts of Astragalus, 12-15 parts of Salvia miltiorrhiza, 15-20 parts of Leonurus japonicus, 9-10 parts of Gastrodia elata, 9-10 parts of Eucommia ulmoides, 12-15 parts of Morus alba, 6-10 parts of Scutellaria baicalensis, and 20-30 parts of raw oysters.

[0014] The Chinese medicine composition provided by the present invention is an empirical prescription obtained by the applicant summarizing many years of clinical experience. By summarizing the long-term clinical diagnosis and treatment experience, it is found that in the prescription composed of the above eight herbs, effectively controlling the dosage of Astragalus, Salvia miltiorrhiza and Leonurus japonicus and the proportion of the three herbs in the prescription will have a significant improvement effect on the symptoms of hypertensive heart failure. In a specific embodiment, the total weight of Astragalus, Salvia miltiorrhiza and Leonurus japonicus in the Chinese medicine composition accounts for 45-65wt%. In addition, the dosage of Astragalus can be increased for patients with qi deficiency symptoms such as shortness of breath and fatigue.

[0015] Illustratively, the Chinese medicine composition includes, by weight: 15 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 15 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Viscum album, 9 parts of Scutellaria baicalensis, and 30 parts of raw oysters.

[0016] Illustratively, the Chinese medicine composition includes, by weight: 20 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 20 parts of Leonurus japonicus, 9 parts of Gastrodia elata, 9 parts of Eucommia ulmoides, 15 parts of Viscum album, 6 parts of Scutellaria baicalensis, and 15 parts of raw oysters.

[0017] Illustratively, the Chinese medicine composition includes, by weight: 15 parts of Astragalus, 10 parts of Salvia miltiorrhiza, 15 parts of Leonurus japonicus, 6 parts of Gastrodia elata, 6 parts of Eucommia ulmoides, 9 parts of Viscum album, 6 parts of Scutellaria baicalensis, and 15 parts of raw oysters.

[0018] Illustratively, the Chinese medicine composition includes, by weight: 20 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Viscum album, 10 parts of Scutellaria baicalensis, and 30 parts of raw oysters.

[0019] Illustratively, the Chinese medicine composition includes, by weight: 20 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 20 parts of Leonurus japonicus, 9 parts of Gastrodia elata, 9 parts of Eucommia ulmoides, 9 parts of Viscum album, 9 parts of Scutellaria baicalensis, and 20 parts of raw oysters.

[0020] Illustratively, the Chinese medicine composition includes, by weight: 20 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Leonurus japonicus, 9 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Viscum album, 9 parts of Scutellaria baicalensis, and 30 parts of raw oysters.

[0021] Illustratively, the Chinese medicine composition includes, by weight: 20 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 20 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Viscum album, 10 parts of Scutellaria baicalensis, and 20 parts of raw oysters.

[0022] Illustratively, the Chinese medicine composition includes, by weight: 20 parts of Astragalus, 10 parts of Salvia miltiorrhiza, 20 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Viscum album, 10 parts of Scutellaria baicalensis, and 20 parts of raw oysters.

[0023] Illustratively, the Chinese medicine composition includes, by weight: 15 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 15 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Viscum album, 6 parts of Scutellaria baicalensis, and 30 parts of raw oysters.

[0024] Illustratively, the Chinese medicine composition includes, by weight: 30 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 15 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Viscum album, 6 parts of Scutellaria baicalensis, and 30 parts of raw oysters.

[0025] Illustratively, the Chinese medicine composition includes, by weight: 15 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 15 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Viscum album, 6 parts of Scutellaria baicalensis, and 20 parts of raw oysters.

[0026] Illustratively, the Chinese medicine composition includes, by weight: 30 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Viscum album, 6 parts of Scutellaria baicalensis, and 20 parts of raw oysters.

[0027] Illustratively, the Chinese medicine composition includes, by weight: 15 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Viscum album, 6 parts of Scutellaria baicalensis, and 20 parts of raw oysters.

[0028] Illustratively, the Chinese medicine composition includes, by weight: 30 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Viscum album, 6 parts of Scutellaria baicalensis, and 30 parts of raw oysters.

[0029] Illustratively, the Chinese medicine composition includes, by weight: 20 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Viscum album, 6 parts of Scutellaria baicalensis, and 20 parts of raw oysters.

[0030] Illustratively, the Chinese medicine composition includes, by weight: 30 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Viscum album, 9 parts of Scutellaria baicalensis, and 20 parts of raw oysters.

[0031] The basic formula of each raw material medicine of the above-mentioned Chinese medicine composition of the present invention can be adjusted according to clinical symptoms on the basis of the above-mentioned Chinese medicine composition in a specific embodiment to achieve the purpose of treating hypertension heart failure and improving certain special clinical symptoms, further enhance the adaptability of the composition of the present invention, and improve the therapeutic effect. These adjustments made based on the basic formula of the present invention are also within the protection scope of this application.

[0032] Unless otherwise specified, the raw materials of the Chinese medicine composition of the present invention can be obtained commercially, and any range recorded in the present invention, including the end values ​​and any numerical value between the end values, and any sub-range of the Chinese medicine composition composed of the end values ​​or any numerical value between the end values, can achieve the purpose of treating hypertensive heart failure.

[0033] To achieve the above second purpose, the technical solution adopted by the present invention includes:

[0034] The invention discloses a traditional Chinese medicine preparation for treating hypertension heart failure, wherein the traditional Chinese medicine preparation uses the traditional Chinese medicine composition as an active ingredient.

[0035] Furthermore, the Chinese medicine preparation also contains pharmaceutically acceptable excipients; illustratively, the excipients include but are not limited to excipients, diluents, carriers, flavoring agents, adhesives, fillers, and the like.

[0036] Furthermore, the dosage form of the Chinese medicine preparation is decoction, granules, capsules, tablets, pills, granules or oral liquid.

[0037] Furthermore, the Chinese medicine composition of the present invention can be prepared into a decoction according to the traditional preparation method of the prescription. Exemplarily, the decoction is prepared according to the following steps:

[0038] Weigh various Chinese medicinal materials according to the weight ratio of the raw materials, add 8-10 times of water to soak for 0.5-3h, boil over high heat first, then simmer over low heat to extract the juice, simmer for 1-2h, filter, collect the filtrate, add 8-10 times of water to the residue for a second decoction, filter, and combine the filtrates to obtain the product.

[0039] Furthermore, the Chinese medicine composition of the present invention can be prepared into granules according to the traditional preparation method of prescriptions. Exemplarily, the granules are prepared according to the following steps:

[0040] Weigh various Chinese medicinal materials according to the weight ratio of the raw materials, add 8-10 times of water for decoction, filter, collect the filtrate, add 8-10 times of water to the filter residue for secondary decoction, filter, combine the filtrates, concentrate to a clear paste, spray dry, sieve, mix and granulate to obtain the paste.

[0041] Furthermore, the Chinese medicine composition of the present invention can be prepared into tablets according to the traditional prescription preparation method. Exemplarily, the tablets are prepared according to the following steps:

[0042] Weigh various Chinese medicinal materials according to the weight ratio of the raw materials, add 8-10 times of water for decoction, filter, collect the filtrate, add 8-10 times of water to the residue for secondary decoction, filter, combine the filtrates, concentrate to a clear paste, and add conventional excipients to make tablets.

[0043] The above exemplary methods for preparing some typical Chinese medicine preparations are provided. Experimental verification shows that the medicines obtained by the above various preparation methods can achieve the therapeutic effects of the medicines.

[0044] To achieve the third objective above, the technical solution adopted by the present invention includes:

[0045] The present invention discloses an application of the above-mentioned traditional Chinese medicine composition or traditional Chinese medicine preparation in preparing a medicine for treating hypertension and heart failure.

[0046] Furthermore, the symptoms of hypertensive heart failure include preserved left ventricular ejection fraction.

[0047] Beneficial effects of the present invention:

[0048] (1) The Chinese medicine composition provided by the present invention conforms to the traditional Chinese medicine syndrome differentiation theory system and the principle of monarch-minister-assistant-adjuvant-guiding compatibility of Chinese medicine, wherein Astragalus is the monarch medicine, Salvia miltiorrhiza, Leonurus japonicus, Gastrodia elata, Eucommia ulmoides, and Morus alba are ministerial medicines, and Scutellaria baicalensis and raw oyster are adjuvant medicines. The combination of these medicines can effectively improve the symptoms of Qi deficiency and blood stasis, and liver and kidney deficiency in patients with hypertension and heart failure, and is particularly suitable for patients with hypertension and heart failure with preserved left ventricular ejection fraction.

[0049] (2) The Chinese medicine composition of the present invention has a clear efficacy in treating hypertensive heart failure. Animal experimental results show that the Chinese medicine composition of the present invention can effectively reduce the left ventricular end-diastolic diameter, left ventricular end-systolic diameter, cardiac organ coefficient (heart mass / body mass, heart mass / tibia length), serum amino-terminal pro-brain natriuretic peptide level, and myocardial tissue collagen volume fraction of heart failure model mice caused by pressure load established by aortic arch constriction (TAC) surgery, and is superior to the positive control drug enalapril in reducing the cardiac organ coefficient and serum amino-terminal pro-brain natriuretic peptide level. The Chinese medicine composition of the present invention can effectively improve the left ventricular ejection fraction and left ventricular short-axis shortening rate of the heart of TAC mice, and the effect is better than the positive control drug enalapril. At the same time, combined with typical cases, it is also proved that the present invention has a significant efficacy in improving the symptoms of hypertensive heart failure. BRIEF DESCRIPTION OF THE DRAWINGS

[0050] Figure 1 Shown are the echocardiograms of four groups of mice in the animal experiment;

[0051] Figure 2 The results of left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), left ventricular ejection fraction (EF), and left ventricular fractional shortening (FS) in four groups of mice in the animal experiment are shown. In the figure, *** indicates p<0.001 compared with the TAC group, and ### indicates p<0.001 compared with the SHAM group;

[0052] Figure 3The results of measuring cardiac organ coefficients [heart weight / body weight (HW / BW), heart weight / tibia length (HW / TL)] of four groups of mice in animal experiments are shown. In the figure, *** indicates p<0.001 compared with the TAC group, and ### indicates p<0.001 compared with the SHAM group;

[0053] Figure 4 The results of measuring serum amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels in four groups of mice in the animal experiment are shown. In the figure, *** indicates p<0.001 compared with the TAC group, and ### indicates p<0.001 compared with the SHAM group;

[0054] Figure 5 The results of Masson staining of myocardial tissue of four groups of mice in animal experiments are shown;

[0055] Figure 6 The results of measuring the collagen volume fraction of myocardial tissue under Masson staining in four groups of mice in the animal experiment are shown. In the figure, *** indicates p < 0.001 compared with the TAC group, and # indicates p < 0.05 compared with the SHAM group;

[0056] Figure 7 The electrophoresis diagrams of TGF-beta 1, Smad2 / 3 and p-Smad2 / 3 pathway proteins in four groups of mice in animal experiments are shown;

[0057] Figure 8 The graph shows the protein expression levels of TGF-beta 1, Smad2 / 3 and p-Smad2 / 3 pathways in four groups of mice in the animal experiment. In the graph, *** indicates p < 0.001 compared with the TAC group, and ### indicates p < 0.001 compared with the SHAM group. DETAILED DESCRIPTION

[0058] In order to more clearly illustrate the present invention, the present invention is further described below in conjunction with preferred embodiments and drawings. It should be clear that the described embodiments are only part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0059] Example 1

[0060] This example provides a traditional Chinese medicine composition for treating hypertensive heart failure, which is made of the following raw materials in the following weight ratio: 15 parts of astragalus, 15 parts of salvia miltiorrhiza, 15 parts of motherwort, 10 parts of gastrodia elata, 10 parts of eucommia, 15 parts of mistletoe, 9 parts of scutellaria, and 30 parts of raw oyster.

[0061] Weigh various Chinese medicinal materials according to the weight ratio of the raw materials, soak them in pure water for 30 minutes, then boil them over high heat, then turn to low heat and simmer for 1 hour. After filtering the residue and collecting the medicinal liquid, continue to add water to the residue and boil it again, decocting it twice, each time for 1 hour, and finally combine the three medicinal liquids to obtain a decoction.

[0062] Example 2

[0063] This example provides a traditional Chinese medicine composition for treating hypertensive heart failure, which is made of the following raw materials in the following weight ratio: 20 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 20 parts of Leonurus japonicus, 9 parts of Gastrodia elata, 9 parts of Eucommia ulmoides, 15 parts of Viscum album, 6 parts of Scutellaria baicalensis, and 15 parts of raw oyster.

[0064] Weigh various Chinese medicinal materials according to the weight ratio of the raw materials, add water and boil for 3 times. For the first decoction, add 10 times the amount of water and boil for 1.5 hours. For the next two decoctions, add 6 times the amount of water and boil for 1 hour. Combine the three filtrates, add appropriate amount of dextrin, concentrate under reduced pressure into a paste, and add starch to make granules.

[0065] Example 3

[0066] This example provides a traditional Chinese medicine composition for treating hypertensive heart failure, which is made of the following raw materials in the following weight ratio: 15 parts of Astragalus, 10 parts of Salvia miltiorrhiza, 15 parts of Leonurus japonicus, 6 parts of Gastrodia elata, 6 parts of Eucommia ulmoides, 9 parts of Viscum album, 6 parts of Scutellaria baicalensis, and 15 parts of raw oyster.

[0067] Weigh various Chinese medicinal materials according to the weight ratio of the raw materials, add water and boil twice, add 8 times the amount of water each time and boil for 1 hour, combine the two filtrates, add appropriate amount of dextrin, concentrate under reduced pressure into a paste, and add conventional excipients to make tablets.

[0068] Example 4

[0069] This example provides a traditional Chinese medicine composition for treating hypertensive heart failure, which is made of the following raw materials in the following weight ratio: 20 parts of astragalus, 15 parts of salvia miltiorrhiza, 30 parts of motherwort, 10 parts of gastrodia elata, 10 parts of eucommia, 15 parts of mistletoe, 10 parts of scutellaria, and 30 parts of raw oyster.

[0070] Weigh various Chinese medicinal materials according to the weight ratio of the raw materials, crush them into fine powder, sieve, mix well, and add 90-110g of refined honey to every 100g of powder to make small honey pills.

[0071] Example 5

[0072] This example provides a traditional Chinese medicine composition for treating hypertensive heart failure, which is made of the following raw materials in the following weight ratio: 20 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 20 parts of Leonurus japonicus, 9 parts of Gastrodia elata, 9 parts of Eucommia ulmoides, 9 parts of Viscum album, 9 parts of Scutellaria baicalensis, and 20 parts of raw oyster.

[0073] Weigh various Chinese medicinal materials according to the weight ratio of the raw materials, add water and boil for 3 times, add 8 times the amount of water for the first decoction and boil for 2 hours, add 6 times the amount of water for the next two decoctions and boil for 1.5 hours, combine the three filtrates, and concentrate under reduced pressure to form a thick paste;

[0074] Take polyethylene glycol (PEG) 6000 and heat it to 135°C in an oil bath, then add the thick paste obtained above, stir continuously to melt it completely, filter it while hot, drop it into liquid paraffin coolant and cool it into pills.

[0075] Example 6

[0076] This example provides a traditional Chinese medicine composition for treating hypertensive heart failure, which is made of the following raw materials in the following weight ratio: 20 parts of astragalus, 15 parts of salvia miltiorrhiza, 30 parts of motherwort, 9 parts of gastrodia elata, 10 parts of eucommia, 15 parts of mistletoe, 9 parts of scutellaria, and 30 parts of raw oyster.

[0077] Weigh various Chinese medicinal materials according to the weight ratio of the raw materials, add water and boil for 3 times, adding 8 times the amount of water each time, boil for 2 hours for the first time, 1.5 hours for the second time, and 1 hour for the third time, combine the three filtrates, add appropriate amount of dextrin, concentrate under reduced pressure to form a thick paste, add distilled water, and stir to make an oral solution.

[0078] Example 7

[0079] This example provides a traditional Chinese medicine composition for treating hypertensive heart failure, which is made of the following raw materials in the following weight ratio: 20 parts of astragalus, 15 parts of salvia miltiorrhiza, 20 parts of motherwort, 10 parts of gastrodia elata, 10 parts of eucommia, 15 parts of mistletoe, 10 parts of scutellaria, and 20 parts of raw oyster.

[0080] Weigh various Chinese medicinal materials according to the weight ratio of the raw materials, add water and boil them twice, add 12 times the amount of water for the first time and boil them for 2 hours, add 8 times the amount of water for the second time and boil them for 1 hour, combine the filtrates, and concentrate them under reduced pressure to form a paste, cool the concentrate to room temperature, add 95% ethanol while stirring to make the alcohol content reach 75%, let it stand and cool for 24 hours, separate the supernatant alcohol solution, wash the precipitate once with 75% ethanol and filter it, separate the supernatant alcohol solution, recover the ethanol under reduced pressure until there is no alcohol taste, add an appropriate amount of dextrin, concentrate under reduced pressure to form a paste, spray dry, and add pharmaceutically acceptable excipients to prepare capsules.

[0081] Example 8

[0082] This example provides a traditional Chinese medicine composition for treating hypertensive heart failure, which is made of the following raw materials in the following weight ratio: 20 parts of astragalus, 10 parts of salvia miltiorrhiza, 20 parts of motherwort, 10 parts of gastrodia elata, 10 parts of eucommia, 15 parts of mistletoe, 10 parts of scutellaria, and 20 parts of raw oyster.

[0083] Weigh various Chinese medicinal materials according to the weight ratio of the raw materials, slice them, add water to cover the materials, soak them for 1 hour, then boil them for 2 hours, separate the residue, add water to the residue and boil them for 3 times, each time adding 6 times the amount of water and boiling for 2 hours, collect the separated medicinal liquid, add appropriate amount of dextrin, evaporate at low temperature to a thick paste, dry at 60℃-80℃, and make it into granules.

[0084] Animal experiments

[0085] The decoction prepared in Example 1 was used in animal experiments.

[0086] In the animal experiment, the applicant used enalapril maleate, a Western medicine with the best efficacy and the widest application range, for comparison to verify the therapeutic effect of the Chinese medicine composition of the present invention.

[0087] Enalapril is an angiotensin converting enzyme inhibitor (ACE inhibitor or ACEI). It can directly inhibit the generation of local AT II in the heart while dilating blood vessels and lowering blood pressure. On the other hand, it can indirectly inhibit the release of catecholamines from cardiac sympathetic nerve endings, thereby reducing the activation of α or β receptors by catecholamine transmitters. These two aspects work together to prevent the occurrence of myocardial hypertrophy. Therefore, enalapril is used to treat hypertension and certain types of congestive heart failure. Enalapril is the second ACEI drug to be marketed after captopril. It not only has a high and lasting antihypertensive effect, but also does not have the side effects unique to captopril. Enalapril was first produced by Merck Sharp & Dohme (MSD) in the form of maleate, with the trade name Vasotec.

[0088] The specific information of Enalapril is as follows:

[0089] Chinese name: Enalapril maleate. Chinese alias: N-[(S)-1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl-L-proline (Z)-2-succinate; Enalapril maleate; Yueningding.

[0090] English name: enalapril maleate; English alias: MK 421maleate; M Glioten; Renitec; Naprilene; CAS number: 76095-16-4.

[0091] Molecular formula: C 24 H 32 N2O9.

[0092] Structural formula:

[0093]

[0094] Molecular weight: 492.51900; Exact mass: 492.21100; PSA: 170.54000; LogP: 1.64520.

[0095] I. Experimental animals and grouping

[0096] Twenty-four SPF-grade male C57BL / 6J mice, 8 weeks old, with a body weight of (22 ± 2) g, were provided by Beijing Huafukang Biotechnology Co., Ltd., license number: SCXK (Jing) 2019-0008. After 5 days of adaptive feeding, a heart failure model induced by pressure load was established by transverse aortic constriction (TAC). This study was approved by the Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences.

[0097] Surgical procedure of aortic arch constriction: Mice were anesthetized by intraperitoneal injection of 0.5% sodium pentobarbital (40 mg / kg), fixed in the supine position, and the surgical area was shaved. The skin was incised along the midline of the neck, and the thyroid gland, fat, and muscle were dissected from the middle to both sides to expose the trachea and sternum. The sternum was longitudinally incised about 5 mm in the middle, and the aortic arch was carefully dissected and exposed to prevent pneumothorax. A 27G constriction needle was ligated with a 6-0 suture between the left common carotid artery and the brachiocephalic trunk. After ligation, the constriction needle was withdrawn, and the sternum and skin were sutured layer by layer with a 5-0 suture. The skin incision was cleaned and disinfected with iodophor. In the sham operation group, except for not performing aortic arch constriction, the remaining surgical procedures were the same as those in the model group. After the operation, the mice were placed on a warming blanket and returned to the cage after waking up.

[0098] The experimental grouping and specific drug administration are as follows:

[0099] Sham operation group (SHAM): 6 mice, gavaged with distilled water;

[0100] Model group (TAC): 6 mice, gavaged with distilled water;

[0101] Traditional Chinese medicine combination group (ZYZH): 6 mice, gavaged with 17.42 g of crude drug of the formula in Example 1 / kg / d;

[0102] Enalapril group (ENA): 6 mice, gavaged with 1.3 mg of enalapril maleate / kg / d, as a positive control for western medicine.

[0103] All drugs were prepared into solutions at 1 ml / 10 g body weight before the experiment and gavaged at equal volume 24 hours after the operation. Standard feed was provided, and free drinking water was available for 8 consecutive weeks.

[0104] II. Comparison of cardiac function parameters of mice in each group

[0105] 1. Experimental method

[0106] At the 8th week, the skin was prepared, and the next day, 0.5% sodium pentobarbital (40 mg / kg) was intraperitoneally injected for anesthesia, and the cardiac function of each group of mice was detected using a two-dimensional and M-mode echocardiography system. The left ventricular motion curve was recorded by short-axis M-mode ultrasound to measure the following indicators: left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs) and systolic function [left ventricular ejection fraction (EF), left ventricular short-axis shortening rate (FS)]. Each sample was measured for 3 cardiac cycles, and the average value was calculated.

[0107] Hypertensive heart failure can cause left ventricular dilatation and decreased left ventricular systolic function. LVIDd and LVIDs are the preferred indicators for judging left ventricular dilatation, and EF and FS are the preferred indicators for judging left ventricular contractility. Therefore, they can be used to evaluate the severity of heart failure.

[0108] 2. Experimental results

[0109] Echocardiogram of mice in each group Figure 1 The measurement results of LVIDd, LVIDs, EF and FS are shown in Table 1 and Figure 2 As shown in the figure, the LVEF value of the TAC group was (48.43±5.42)%, slightly less than 50%. It can be considered that the animal model in this animal experiment basically conforms to the heart failure with preserved ejection fraction of hypertension. The LVIDd and LVIDs values ​​of the TAC group were significantly higher than those of the SHAM group (p<0.001), and the LVIDd and LVIDs values ​​of the ZYZH group and the ENA group were significantly lower than those of the TAC group (p<0.001); the EF and FS values ​​of the TAC group were significantly lower than those of the SHAM group (p<0.001), and the EF and FS values ​​of the ZYZH group and the ENA group were significantly higher than those of the TAC group (p<0.001). Among them, the EF and FS values ​​of the ZYZH group were increased by 1.69% and 2.08% respectively compared with those of the ENA group.

[0110] Table 1 Echocardiographic parameters of mice ( n=6)

[0111] Grouping ZYZH Group ENA group TAC Group SHAM Group LVIDd(mm) <![CDATA[3.15±0.31 *** ]]> <![CDATA[3.03±0.19 *** ]]> <![CDATA[4.00±0.26 ### ]]> 3.10±0.21 LVIDs(mm) <![CDATA[1.60±0.25 *** ]]> <![CDATA[1.60±0.19 *** ]]> <![CDATA[3.04±0.22 ### ]]> 1.58±0.12 LVEF (%) <![CDATA[81.50±5.11 *** ]]> <![CDATA[79.81±4.01 *** ]]> <![CDATA[48.43±5.42 ### ]]> 81.88±1.55 LVFS(%) <![CDATA[49.25±5.63 *** ]]> <![CDATA[47.17±3.89 *** ]]> <![CDATA[24.13±3.30 ### ]]> 49.25±1.69

[0112] Note: Compared with the TAC group, ***<0.001; compared with the SHAM group, ###<0.001.

[0113] 3. Heart organ coefficient

[0114] 1. Experimental Methods

[0115] Before sampling, the mice were weighed and recorded for body weight (BW). After blood was collected from the abdominal aorta, the mice were killed by cervical dislocation, and the intact heart was quickly removed. The blood stains were rinsed with pre-cooled PBS buffer, and the residual blood in the heart cavity was drained. The heart was placed on an ice tray to remove excess tissue, and the surface moisture was absorbed with clean filter paper. The heart weight (HW) was weighed and recorded using an electronic analytical balance. The weighed heart was placed in cold PBS, a ruler was placed around it, and the morphology of the heart was recorded by taking pictures. The tibia of the right lower limb of the mouse was separated, and the tibia length (TL) was measured and recorded with a vernier caliper, and the ratios of HW / BW and HW / TL were calculated. The cardiac organ coefficient can indicate the condition of myocardial hypertrophy and reflect the ventricular remodeling of hypertensive heart failure.

[0116] 2. Experimental results

[0117] The results of the heart organ coefficient measurements of mice in each group are shown in Table 2 and Figure 3 As shown in the data, the ratios of HW / BW and HW / TL in the TAC group were significantly higher than those in the SHAM group (p < 0.001), while the HW / BW and HW / TL values ​​in the ZYZH group and the ENA group were significantly lower than those in the TAC group (p < 0.001), and the HW / BW and HW / TL values ​​in the ZYZH group were 0.28 mg / g and 0.82 mg / mm lower than those in the ENA group, respectively.

[0118] Table 2 Comparison of mouse heart organ coefficients ( n=6)

[0119] Grouping ZYZH Group ENA group TAC Group SHAM Group HW / BW(mg / g) <![CDATA[4.43±0.18 *** ]]> <![CDATA[4.71±0.37 *** ]]> <![CDATA[5.54±0.33 ### ]]> 4.47±0.12 HW / TL(mg / mm) <![CDATA[7.58±0.34 *** ]]> <![CDATA[8.40±0.56 *** ]]> <![CDATA[10.85±0.70 ### ]]> 7.28±0.25

[0120] Note: Compared with the TAC group, ***<0.001; compared with the SHAM group, ###<0.001.

[0121] 4. Elisa to detect heart failure marker levels

[0122] 1. Experimental Methods

[0123] The blood samples were collected from the abdominal aorta and centrifuged at 4000r / min for 15 minutes, and the upper serum was taken for later use. The serum amino-terminal pro-brain natriuretic peptide (NT-proBNP) level was detected by Elisa competitive method strictly according to the steps of Elisa kit. NT-proBNP is an important indicator for diagnosing heart failure and indicates the severity of heart failure.

[0124] 2. Experimental results

[0125] The results of serum NT-proBNP level measurement in each group of mice are shown in Table 3 and Figure 4As shown, the NT-proBNP value of the TAC group was significantly higher than that of the SHAM group (p<0.001), the NT-proBNP values ​​of the ZYZH group and the ENA group were significantly lower than those of the TAC group (p<0.001), and the NT-proBNP value of the ZYZH group was 10.10 pg / ml lower than that of the ENA group.

[0126] Table 3. Serum NT-proBNP levels in mice ( n=6)

[0127]

[0128] Note: Compared with the TAC group, ***<0.001; compared with the SHAM group, ###<0.001.

[0129] 5. Evaluation of Myocardial Fibrosis

[0130] 1. Experimental Methods

[0131] After the heart specimens were removed, they were fixed with 4% paraformaldehyde solution for 24 hours, dehydrated and embedded in paraffin. Masson staining was performed on the cardiomyocytes, and the collagen volume fraction was calculated using ImageJ to evaluate the myocardial fibrosis.

[0132] 2. Experimental results

[0133] Masson staining of myocardial cells in each group of mice Figure 5 As shown in the figure, a small amount of blue collagen fibers can be seen in the SHAM group; a large amount of blue collagen fibers can be seen in the TAC group; and the blue collagen fibers in the ZYZH group are significantly less than those in the TAC group. The same cross-sectional area of ​​4 different hearts was selected for each group, and 4 pathological images were taken at 40× magnification to calculate the collagen volume fraction of the myocardial tissue of each group of mice under Masson staining, as shown in Table 4 and Figure 6 The collagen volume fraction in the TAC group was significantly higher than that in the SHAM group (p<0.05), and the collagen volume fraction in the ZYZH group and the ENA group was significantly lower than that in the TAC group (p<0.001).

[0134] Table 4 Collagen volume fraction of myocardial tissue of each group of mice under Masson staining ( n=4)

[0135] Grouping ZYZH Group ENA group TAC Group SHAM Group Collagen volume fraction (%) <![CDATA[10.82±2.91 *** ]]> <![CDATA[8.34±0.46 *** ]]> <![CDATA[26.57±0.45 # ]]> 4.62±0.73

[0136] Note: Compared with the TAC group, ***<0.001; compared with the SHAM group, #<0.05.

[0137] VI. Western Blot Detection of Myocardial Tissue Protein Expression

[0138] 1. Experimental Methods

[0139] The frozen ventricular tissue was homogenized and the expressions of pathway proteins TGF-beta 1, Smad2 / 3 and p-Smad2 / 3 were evaluated by SDS-polyacrylamide gel electrophoresis, transfer to PVDF membrane, blocking, hybridization and chemiluminescence imaging.

[0140] In fibrotic diseases, activation of the TGF-beta / Smad signaling pathway causes fibroblasts to proliferate and differentiate into myofibroblasts, synthesizing a large amount of collagen, resulting in excessive deposition of extracellular matrix, leading to the occurrence of fibrotic diseases. Activation of the TGF-beta / Smad signaling pathway is an important mechanism of myocardial fibrosis, and TGF-beta 1, Smad2 / 3 and p-Smad2 / 3 are key proteins in the TGF-beta / Smad signaling pathway.

[0141] 2. Experimental results

[0142] The electrophoresis diagrams of pathway proteins TGF-beta 1, Smad2 / 3 and p-Smad2 / 3 in each group of mice are shown in Figure 2. Figure 7 As shown, the expression levels of pathway proteins TGF-beta 1, Smad2 / 3 and p-Smad2 / 3 in each group of mice were Figure 8 As shown in the data, TAC surgery caused a significant increase in the expression levels of pathway proteins TGF-beta 1, Smad2 / 3 and p-Smad2 / 3 (p < 0.001), and ZYZH and ENA treatment could inhibit the expression of TGF-beta 1, Smad2 / 3 and p-Smad2 / 3.

[0143] Therefore, the characterization of the above experiments and data results indicates that the Chinese medicine composition provided by the present invention has a good effect in improving hypertensive heart failure.

[0144] The pharmaceutical composition of the present invention is an in-hospital preparation. Through the effect verification of nearly a thousand clinical cases, it has a significant therapeutic effect on hypertension heart failure caused by qi deficiency and blood stasis, liver and kidney deficiency, and can reduce the use of Western medicine to achieve the purpose of treatment. Especially for patients with poor results of Western medicine treatment, it can improve the body's function, control blood pressure, improve cardiac function, and improve the quality of life, achieving the therapeutic effect of both the root and the target. The following are typical cases selected from clinical practice.

[0145] Typical Cases

[0146] Case 1

[0147] Zhang XX, male, 61 years old, first visit on September 6, 2022:

[0148] Chief complaint: intermittent dizziness for 20 years, aggravated by shortness of breath for 4 days.

[0149] Current medical history: 20 years ago, he developed dizziness after emotional excitement. He was diagnosed with hypertension and given nifedipine controlled-release tablets 30 mg 1 / day for antihypertensive treatment. Later, he had intermittent dizziness. In October 2010, he was treated at the Fuwai Hospital of the Chinese Academy of Medical Sciences. His blood pressure was measured at 150 / 100 mmHg. He was given nifedipine controlled-release tablets 30 mg 1 / day and metoprolol succinate sustained-release tablets 47.5 mg 1 / day. His dizziness improved and his blood pressure was controlled at 130-140 / 90 mmHg. In October 2024, he developed dizziness, palpitations, and shortness of breath. At the Fuwai Hospital of the Chinese Academy of Medical Sciences, his blood pressure was measured at 150 / 90 mmHg. Cardiac ultrasound showed: left ventricular ejection fraction 52%, left atrial diameter 40 mm, left ventricular end-diastolic diameter 56 mm, left ventricular end-systolic diameter 42 mm, ventricular septum 13 mm, and left ventricular diastolic function decreased. Amino-terminal pro-brain natriuretic peptide (NT-proBNP) 512 pg / ml. Diagnosed with "heart failure with preserved ejection fraction", he was given sacubitril valsartan sodium tablets 100 mg 1 / day and metoprolol succinate sustained-release tablets 47.5 mg 1 / day. In the past 4 days, his dizziness has worsened, accompanied by shortness of breath, and he is now being treated in our hospital.

[0150] Current symptoms: dizziness, shortness of breath, fatigue, occasional chest tightness, spontaneous sweating, bitter taste in the mouth, hot flashes, night sweats, frequent dreams, and normal bowel movements.

[0151] Tongue and pulse: dark red tongue with petechiae, little coating, and thready pulse.

[0152] Past medical history: history of hyperlipidemia for 10 years, oral atorvastatin calcium tablets 20 mg 1 / night for lipid-lowering; denial of other chronic disease history.

[0153] Personal history: Denies history of smoking and drinking.

[0154] Family history: No relevant family history.

[0155] Allergy history: Denies history of food or drug allergy.

[0156] Oral medications: sacubitril valsartan sodium tablets 100 mg 1 / day, metoprolol succinate sustained-release tablets 47.5 mg 1 / day, atorvastatin calcium tablets 20 mg 1 / night.

[0157] Diagnosis: Western medicine diagnosis: hypertension, heart failure with preserved ejection fraction, and hyperlipidemia.

[0158] TCM diagnosis: vertigo (Qi deficiency, blood stasis, liver and kidney deficiency).

[0159] Treatment method: Invigorate Qi and activate blood circulation, nourish the liver and kidneys.

[0160] Prescription: 15g Astragalus, 15g Salvia, 15g Leonurus, 10g Gastrodia, 10g Eucommia, 15g Viscum, 6g Scutellaria, 30g raw oyster.

[0161] Explanation of the prescription: According to the symptoms, tongue and pulse, the patient was diagnosed with qi deficiency, blood stasis, and liver and kidney deficiency, so I gave the original prescription.

[0162] Second visit on November 11, 2022:

[0163] Current symptoms: After taking the above prescription, the frequency of dizziness attacks has decreased, spontaneous sweating, hot flashes, night sweats, bitter taste in the mouth, and frequent dreams have been alleviated, there is no chest tightness, but shortness of breath and fatigue still exist, appetite is good, and bowel movements are regular.

[0164] Tongue and pulse: pale and dark tongue, thin white fur, and fine and stringy pulse.

[0165] Oral medication: Sacubitril / valsartan sodium tablets 100 mg 1 / day, atorvastatin calcium tablets 20 mg 1 / night.

[0166] Auxiliary examination: On December 23, 2022, the 24-hour dynamic blood pressure was checked at Anzhen Hospital Affiliated to Capital Medical University, showing: 24-hour average systolic pressure 132mmHg, 24-hour average diastolic pressure 86mmHg. Cardiac ultrasound: left ventricular ejection fraction 62%, left atrial diameter 36mm, left ventricular end-diastolic diameter 52mm, left ventricular end-systolic diameter 39mm, ventricular septum 11mm. NT-proBNP 218pg / ml.

[0167] Prescription: Astragalus 30g, Salvia miltiorrhiza 15g, Leonurus japonicus 15g, Gastrodia elata 10g, Eucommia ulmoides 10g, Viscum album 15g, Scutellaria baicalensis 6g, and raw oyster 30g.

[0168] Explanation of the prescription: After taking the above prescription, the patient's symptoms improved, but he still had symptoms of qi deficiency such as shortness of breath and fatigue, so the dosage of astragalus was increased to strengthen the qi.

[0169] Third visit on January 13, 2023:

[0170] Current symptoms: After taking the above medicine, the frequency and severity of dizziness and shortness of breath have improved significantly compared to before, there is no spontaneous sweating, hot flashes, night sweats, or bitter taste in the mouth, fatigue has improved, appetite and sleep are good, and bowel movements are normal.

[0171] Tongue and pulse: pale and dark tongue, thin white fur, and fine and stringy pulse.

[0172] Auxiliary examination: On March 29, 2023, the 24-hour dynamic blood pressure was checked at Anzhen Hospital Affiliated to Capital Medical University, showing: 24-hour average systolic pressure 129mmHg, 24-hour average diastolic pressure 81mmHg. Cardiac ultrasound: left ventricular ejection fraction 62%, left atrial diameter 36mm, left ventricular end-diastolic diameter 52mm, left ventricular end-systolic diameter 38mm, ventricular septum 11mm. NT-proBNP 109pg / ml.

[0173] Prescription: Astragalus 30g, Salvia miltiorrhiza 15g, Leonurus japonicus 15g, Gastrodia elata 10g, Eucommia ulmoides 10g, Viscum album 15g, Scutellaria baicalensis 6g, and raw oyster 30g.

[0174] Explanation of the prescription: The patient took the prescription three times in 4 months since the first visit. During this period, the use of antihypertensive drugs was reduced. The frequency and severity of dizziness and shortness of breath were significantly improved. The symptoms of fatigue, spontaneous sweating, hot flashes, night sweats, and bitter mouth were improved. The results of the 24-hour dynamic blood pressure reexamination were normal, and the cardiac ultrasound indicators improved. The original prescription was effective. The previous prescription was used and continued for 1 month to consolidate the therapeutic effect. Follow up if there is any discomfort.

[0175] Case 2

[0176] Wang Moumou, female, 64 years old, first visit on March 5, 2019:

[0177] Chief complaint: intermittent dizziness for 19 years, worsening for 1 week.

[0178] Current medical history: 19 years ago, the patient experienced dizziness after exertion, and his blood pressure was 200 / 70 mmHg. He was diagnosed with "hypertension" at Fuxing Hospital Affiliated to Capital Medical University and given 5 mg 1 / day of levamlodipine besylate for antihypertensive treatment. After taking the medicine, his blood pressure was not well controlled, fluctuating between 150-160 / 70 mmHg, but he did not pay much attention to it. In December 2010, the patient's dizziness worsened after exertion, and his blood pressure was measured at 190 / 75 mmHg at Anzhen Hospital Affiliated to Capital Medical University. He was given losartan potassium hydrochlorothiazide tablets 100 mg / 12.5 mg 1 / day and bisoprolol fumarate 5 mg 1 / day, and his blood pressure was controlled at 130 / 70 mmHg. On February 26, 2019, he developed chest tightness and shortness of breath. A cardiac ultrasound test at Fuxing Hospital Affiliated to Capital Medical University showed: left ventricular ejection fraction 54%, left atrial diameter 38mm, left ventricular end-diastolic diameter 51mm, left ventricular end-systolic diameter 40mm, interventricular septum 13mm, and left ventricular diastolic function decreased. NT-proBNP 691pg / ml. Diagnosis of "heart failure with preserved ejection fraction". Dizziness worsened 1 week ago, and he is now receiving treatment in our hospital.

[0179] Current symptoms: dizziness, shortness of breath, fatigue, occasional chest tightness or pain, spontaneous sweating, bitter taste in the mouth, hot flashes and night sweats, and normal bowel movements.

[0180] Tongue and pulse: The tongue is dark red with petechiae, less coating, and the pulse is weak and stringy.

[0181] Past medical history: history of type 2 diabetes for 10 years, taking oral metformin 0.5g 3 / day to lower blood sugar; denies history of other chronic diseases.

[0182] Personal history: Denies history of smoking and drinking.

[0183] Family history: No relevant family history.

[0184] Allergy history: Denies any history of food or drug allergy.

[0185] Oral medications: enteric-coated aspirin tablets 100 mg 1 / day, metformin 0.5 g 3 / day, losartan potassium and hydrochlorothiazide tablets 100 mg / 12.5 mg 1 / day, bisoprolol fumarate 5 mg 1 / day, sacubitril valsartan sodium tablets 50 mg 1 / day.

[0186] Diagnosis: Western medicine diagnosis: hypertension, heart failure with preserved ejection fraction, and type 2 diabetes.

[0187] TCM diagnosis: vertigo (Qi deficiency, blood stasis, liver and kidney deficiency).

[0188] Treatment method: Invigorate Qi and activate blood circulation, nourish the liver and kidneys.

[0189] Prescription: 15g Astragalus, 15g Salvia miltiorrhiza, 15g Leonurus japonicus, 10g Gastrodia elata, 10g Eucommia ulmoides, 15g Viscum album, 6g Scutellaria baicalensis, 20g raw oyster.

[0190] Explanation of the prescription: According to the symptoms, tongue and pulse, the patient was diagnosed with qi deficiency, blood stasis, and liver and kidney deficiency, so I gave the original prescription.

[0191] Second visit on June 7, 2019:

[0192] Current symptoms: After taking the above medicine, the frequency and severity of dizziness attacks have decreased, hot flashes, night sweats and bitter taste in the mouth have been alleviated, and there is no chest tightness or pain. However, there is still shortness of breath, fatigue and spontaneous sweating, but appetite and sleep are good, and bowel movements are normal.

[0193] Tongue and pulse: Pale and dark tongue with petechiae, thin white fur, and thready pulse.

[0194] Auxiliary examination: On June 1, 2019, the 24-hour dynamic blood pressure was checked at Anzhen Hospital Affiliated to Capital Medical University, showing: 24-hour average systolic pressure 125mmHg, 24-hour average diastolic pressure 76mmHg. Cardiac ultrasound: left ventricular ejection fraction 67%, left atrial diameter 34mm, left ventricular end-diastolic diameter 45mm, left ventricular end-systolic diameter 33mm, ventricular septum 11mm. NT-proBNP 124pg / ml.

[0195] Oral medications: enteric-coated aspirin tablets 100 mg 1 / day, metformin 0.5 g 3 / day, losartan potassium and hydrochlorothiazide tablets 100 mg / 12.5 mg 1 / day, sacubitril valsartan sodium tablets 50 mg 1 / day.

[0196] Prescription: Astragalus 30g, Salvia miltiorrhiza 15g, Leonurus japonicus 30g, Gastrodia elata 10g, Eucommia ulmoides 10g, Viscum album 15g, Scutellaria baicalensis 6g, and raw oyster 20g.

[0197] Explanation of the prescription: The patient's condition has improved significantly after taking the medicine for more than 3 months since the first visit. During this period, the use of antihypertensive drugs was reduced, but there were still symptoms of qi deficiency such as shortness of breath, fatigue, and spontaneous sweating. The results of the 24-hour dynamic blood pressure reexamination were normal, and the cardiac ultrasound indicators improved. The dose of Astragalus was increased to 30g and the dose of Leonurus to 30g to strengthen qi and blood circulation. The other symptoms were all improved. The original prescription was effective, and the dose was slightly increased or decreased. Continue to take the above prescription for 1 month to consolidate the therapeutic effect. Follow up if there is any discomfort.

[0198] Case 3

[0199] Sun, female, 59 years old, first visit on December 29, 2020:

[0200] Chief complaint: intermittent dizziness for 19 years, worsening for 10 days.

[0201] Current medical history: 19 years ago, the patient developed dizziness and headache after emotional excitement and fatigue. He was treated at Anzhen Hospital Affiliated to Capital Medical University. The clinic blood pressure was 203 / 100mmHg. He was diagnosed with "hypertension" and given intravenous antihypertensive treatment. Later, he took regular oral administration of 0.15g 1 / day of irbesartan and 5mg 1 / day of amlodipine besylate, and his symptoms improved. 8 years ago, the frequency of dizziness increased, accompanied by chest tightness. The self-monitored blood pressure fluctuated between 150-160 / 90mmHg, but he did not pay attention to it. 10 days ago, the dizziness worsened, and he was treated at Anzhen Hospital Affiliated to Capital Medical University. The clinic blood pressure was 170 / 100mmHg. Cardiac ultrasound showed: left ventricular ejection fraction 57%, left atrial diameter 40mm, left ventricular end-diastolic diameter 53mm, left ventricular end-systolic diameter 44mm, ventricular septum 13mm, and left ventricular diastolic function decreased. NT-proBNP 711pg / ml. The patient was diagnosed with "heart failure with preserved ejection fraction".

[0202] Current symptoms: dizziness, shortness of breath, obvious fatigue, occasional chest tightness, dry mouth, bitter taste in the mouth, hot flashes, night sweats, difficulty falling asleep, frequent dreams, and regular bowel movements.

[0203] Tongue and pulse: The tongue is dark red with ecchymosis, less coating, and the pulse is stringy and fine.

[0204] Past medical history: history of hyperlipidemia for 10 years, oral atorvastatin calcium tablets 20 mg 1 / night for lipid-lowering; denial of other chronic disease history.

[0205] Personal history: Denies history of smoking and drinking.

[0206] Family history: No relevant family history.

[0207] Allergy history: Denies any history of food or drug allergy.

[0208] Oral medications: enteric-coated aspirin tablets 100 mg 1 / day, atorvastatin calcium tablets 20 mg 1 / night, irbesartan and hydrochlorothiazide tablets 100 mg / 12.5 mg 1 / day, levamlodipine besylate 5 mg 1 / day, sacubitril valsartan sodium tablets 100 mg 1 / day.

[0209] Diagnosis: Western medicine diagnosis: hypertension, heart failure with preserved ejection fraction, and hyperlipidemia.

[0210] TCM diagnosis: vertigo (Qi deficiency, blood stasis, liver and kidney deficiency).

[0211] Treatment method: Invigorate Qi and activate blood circulation, nourish the liver and kidneys.

[0212] Prescription: 15g Astragalus, 15g Salvia miltiorrhiza, 30g Leonurus japonicus, 10g Gastrodia elata, 10g Eucommia ulmoides, 15g Viscum album, 6g Scutellaria baicalensis, 20g raw oyster.

[0213] Explanation of the prescription: According to the symptoms, tongue and pulse, the patient was diagnosed with qi deficiency, blood stasis, and liver and kidney deficiency, so I gave the original prescription.

[0214] Second visit on February 26, 2021:

[0215] Current symptoms: After taking the above prescription, the frequency and severity of dizziness attacks have decreased compared to before, but shortness of breath, fatigue, and difficulty falling asleep still exist. Hot flashes, night sweats, and nightmares have been alleviated, and there is no bitter taste in the mouth or chest tightness. Appetite is good, and bowel movements are normal.

[0216] Tongue and pulse: dark tongue, thin white fur, and fine and stringy pulse.

[0217] Prescription: Astragalus 30g, Salvia miltiorrhiza 15g, Leonurus japonicus 30g, Gastrodia elata 10g, Eucommia ulmoides 10g, Viscum album 15g, Scutellaria baicalensis 6g, and raw oyster 30g.

[0218] Explanation of the prescription: After taking the above prescription, the patient's symptoms improved, but he still had symptoms of qi deficiency such as shortness of breath and fatigue, so the dosage of astragalus was increased to strengthen the qi; the patient still had symptoms of poor sleep, so the dosage of raw oyster was increased to calm the nerves.

[0219] Third visit on April 30, 2021

[0220] Current symptoms: Dizziness has basically disappeared, shortness of breath, fatigue, difficulty falling asleep, hot flashes, night sweats, and nightmares have been significantly improved, appetite and sleep are good, and bowel movements are normal.

[0221] Tongue and pulse: pale and dark tongue, thin white fur, and thin pulse.

[0222] Auxiliary examination: On April 1, 2021, the 24-hour dynamic blood pressure was checked at Anzhen Hospital Affiliated to Capital Medical University, showing: 24-hour average systolic pressure 135mmHg, 24-hour average diastolic pressure 86mmHg. Cardiac ultrasound: left ventricular ejection fraction 65%, left atrial diameter 36mm, left ventricular end-diastolic diameter 48mm, left ventricular end-systolic diameter 37mm, ventricular septum 11mm. NT-proBNP 101pg / ml.

[0223] Oral medications: enteric-coated aspirin tablets 100 mg 1 / day, atorvastatin calcium tablets 20 mg 1 / night, irbesartan and hydrochlorothiazide tablets 100 mg / 12.5 mg 1 / day, sacubitril valsartan sodium tablets 100 mg 1 / day.

[0224] Prescription: Astragalus 30g, Salvia miltiorrhiza 15g, Leonurus japonicus 30g, Gastrodia elata 10g, Eucommia ulmoides 10g, Viscum album 15g, Scutellaria baicalensis 6g, and raw oyster 30g.

[0225] Explanation of the prescription: The patient took the prescription three times in 4 months since the first visit. During this period, the use of antihypertensive drugs was reduced. The patient's symptoms of dizziness, shortness of breath, fatigue, spontaneous sweating, hot flashes, night sweats, bitter mouth, etc. were significantly improved. The results of the 24-hour dynamic blood pressure reexamination were normal, and the cardiac ultrasound indicators improved. The original prescription was effective. The last prescription was used and continued for 1 month to consolidate the therapeutic effect. Follow up if there is any discomfort.

[0226] Case 4

[0227] Jin Moumou, female, 77 years old, first visit on December 29, 2020:

[0228] Chief complaint: intermittent dizziness and headache for more than 10 years, aggravated for 1 month.

[0229] Current medical history: The patient experienced dizziness after exertion more than 10 years ago, and the highest self-measured blood pressure was 170 / 57 mmHg. He was diagnosed with "hypertension" at Xuanwu Hospital Affiliated to Capital Medical University and given 5 mg of amlodipine besylate 1 / day to lower blood pressure, and his blood pressure was controlled at 120-130 / 40-50 mmHg. On December 17, 2020, the patient experienced dizziness and shortness of breath, and his self-measured blood pressure was 150 / 90 mmHg. Cardiac ultrasound at Xuanwu Hospital Affiliated to Capital Medical University showed: left ventricular ejection fraction 51%, left atrial diameter 41 mm, left ventricular end-diastolic diameter 51 mm, left ventricular end-systolic diameter 40 mm, ventricular septum 13 mm, and decreased left ventricular diastolic function. NT-proBNP 522 pg / ml. Diagnosis of "heart failure with preserved ejection fraction". He was given candecibilone tablets 16mg / 12.5mg 1 / day and sacubitril valsartan sodium tablets 50mg 1 / day, but still had dizziness. He is now receiving treatment in our hospital.

[0230] Current symptoms: dizziness, shortness of breath, obvious fatigue, occasional chest tightness and pain, dry mouth and bitter taste, hot flashes and night sweats, shallow sleep and easy awakening, and regular bowel movements.

[0231] Tongue and pulse: The tongue is dark purple with petechiae, the tongue coating is thin white, and the pulse is stringy and fine.

[0232] Past medical history: 10-year history of hyperlipidemia, taking rosuvastatin calcium 10 mg 1 / night orally for lipid-lowering; 20-year history of type 2 diabetes, taking metformin 0.5 g 3 / day orally for blood sugar lowering; denies any other chronic disease history.

[0233] Personal history: Denies history of smoking and drinking.

[0234] Family history: No relevant family history.

[0235] Allergy history: Denies any history of food or drug allergy.

[0236] Oral medications: Candesertioprine tablets 16mg / 12.5mg 1 / day, sacubitril valsartan sodium tablets 50mg 1 / day, rosuvastatin calcium 10mg 1 / night, metformin 0.5g 3 / day.

[0237] Diagnosis: Western medicine diagnosis: hypertension, heart failure with preserved ejection fraction, hyperlipidemia, and type 2 diabetes.

[0238] TCM diagnosis: vertigo (Qi deficiency, blood stasis, liver and kidney deficiency).

[0239] Treatment method: Invigorate Qi and activate blood circulation, nourish the liver and kidneys.

[0240] Prescription: Astragalus 20g, Salvia miltiorrhiza 15g, Leonurus japonicus 30g, Gastrodia elata 10g, Eucommia ulmoides 10g, Viscum album 15g, Scutellaria baicalensis 6g, and raw oyster 20g.

[0241] Explanation of the prescription: According to the symptoms, tongue and pulse, the patient was diagnosed with qi deficiency, blood stasis, and liver and kidney deficiency, so I gave the original prescription.

[0242] Second visit on February 26, 2021:

[0243] Current symptoms: After taking the above medicine, the frequency and severity of dizziness attacks have decreased compared to before, but shortness of breath, fatigue, and bitter taste in the mouth still exist. Shallow sleep, hot flashes and night sweats have been alleviated, and dry mouth, chest tightness or chest pain have disappeared. Appetite is good, and bowel movements are normal.

[0244] Tongue and pulse: pale and dark tongue, thin white fur, and fine and stringy pulse.

[0245] Oral medications: Candesartan cilexetil tablets 8 mg 1 / day, sacubitril valsartan sodium tablets 50 mg 1 / day, rosuvastatin calcium 10 mg 1 / night, metformin 0.5 g 3 / day.

[0246] Prescription: Astragalus 30g, Salvia miltiorrhiza 15g, Leonurus japonicus 30g, Gastrodia elata 10g, Eucommia ulmoides 10g, Viscum album 15g, Scutellaria baicalensis 9g, and raw oyster 20g.

[0247] Explanation of the prescription: After taking the above prescription, the patient's symptoms improved, but he still had symptoms of qi deficiency such as shortness of breath and fatigue, so the dosage of Astragalus was increased to strengthen the qi; the patient still had symptoms of bitter taste in the mouth, so the dosage of Scutellaria baicalensis was increased to clear the liver heat.

[0248] Third visit on April 30, 2021:

[0249] Current symptoms: Dizziness has basically disappeared; shortness of breath, fatigue, bitter taste in the mouth, shallow sleep, hot flashes and night sweats have been significantly improved; appetite is good; bowel movements are normal.

[0250] Tongue and pulse: pale and dark tongue, thin white fur, and fine and stringy pulse.

[0251] Auxiliary examination: On April 20, 2021, the 24-hour dynamic blood pressure was checked at Xuanwu Hospital Affiliated to Capital Medical University, showing: 24-hour average systolic pressure 127mmHg, 24-hour average diastolic pressure 75mmHg. Cardiac ultrasound showed: left ventricular ejection fraction 64%, left atrial diameter 36mm, left ventricular end-diastolic diameter 46mm, left ventricular end-systolic diameter 37mm, ventricular septum 11mm. NT-proBNP 97pg / ml.

[0252] Prescription: Astragalus 30g, Salvia miltiorrhiza 15g, Leonurus japonicus 30g, Gastrodia elata 10g, Eucommia ulmoides 10g, Viscum album 15g, Scutellaria baicalensis 9g, and raw oyster 20g.

[0253] Explanation of the prescription: The patient's condition has improved significantly after taking the medicine for more than 4 months since the first visit. During this period, the use of antihypertensive drugs has been reduced. The results of the 24-hour dynamic blood pressure reexamination are normal, and the cardiac ultrasound indicators have improved. The original prescription is effective. Keep the previous prescription and continue to take the above prescription for 1 month to consolidate the therapeutic effect. Follow up if there is any discomfort.

[0254] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not limitations on the implementation methods of the present invention. For ordinary technicians in the relevant field, other different forms of changes or modifications can be made based on the above description. It is impossible to list all the implementation methods here. All obvious changes or modifications derived from the technical solution of the present invention are still within the protection scope of the present invention.

Claims

1. A Chinese medicine composition for treating hypertensive heart failure, characterized in that: By weight, the raw materials include the following parts by weight: 9-30 parts of Astragalus, 10-15 parts of Salvia miltiorrhiza, 9-30 parts of Leonurus japonicus, 3-10 parts of Gastrodia elata, 6-10 parts of Eucommia ulmoides, 9-15 parts of Morus alba, 3-10 parts of Scutellaria baicalensis, and 9-30 parts of raw oyster.

2. The Chinese medicine composition according to claim 1, characterized in that: By weight, the raw materials include the following parts by weight: 15-30 parts of Astragalus, 12-15 parts of Salvia miltiorrhiza, 15-20 parts of Leonurus japonicus, 9-10 parts of Gastrodia elata, 9-10 parts of Eucommia ulmoides, 12-15 parts of Morus alba, 6-10 parts of Scutellaria baicalensis, and 20-30 parts of raw oysters.

3. The Chinese medicine composition according to claim 1, characterized in that The total weight of the astragalus, salvia miltiorrhiza and motherwort accounts for 45-65wt% of the traditional Chinese medicine composition.

4. The Chinese medicine composition according to claim 1, characterized in that: The Chinese medicine composition comprises, by weight: 15 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 15 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Morus alba, 9 parts of Scutellaria baicalensis, 30 parts of raw oyster; or 20 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 20 parts of Leonurus japonicus, 9 parts of Gastrodia elata, 9 parts of Eucommia ulmoides, 15 parts of Morus alba, 6 parts of Scutellaria baicalensis, 15 parts of raw oyster; or 15 parts of Astragalus, 10 parts of Salvia miltiorrhiza, 15 parts of Leonurus japonicus, 6 parts of Gastrodia elata, 6 parts of Eucommia ulmoides, 9 parts of Morus alba, 6 parts of Scutellaria baicalensis, 15 parts of raw oyster; or 20 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Morus alba, 10 parts of Scutellaria baicalensis, 30 parts of raw oyster; or 20 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 20 parts of Leonurus japonicus, 9 parts of Gastrodia elata, 9 parts of Eucommia ulmoides, 9 parts of Morus alba, 9 parts of Scutellaria baicalensis, 20 parts of raw oyster; or 20 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Leonurus japonicus, 9 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Morus alba, 9 parts of Scutellaria baicalensis, 30 parts of raw oyster; or 20 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 20 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Morus alba, 10 parts of Scutellaria baicalensis, 20 parts of raw oyster; or 20 parts of Astragalus, 10 parts of Salvia miltiorrhiza, 20 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Morus alba, 10 parts of Scutellaria baicalensis, 20 parts of raw oyster; or 15 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 15 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Morus alba, 6 parts of Scutellaria baicalensis, 30 parts of raw oyster; or 30 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 15 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Morus alba, 6 parts of Scutellaria baicalensis, 30 parts of raw oyster; or 15 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 15 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Morus alba, 6 parts of Scutellaria baicalensis, 20 parts of raw oyster; or 30 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Morus alba, 6 parts of Scutellaria baicalensis, 20 parts of raw oyster; or 15 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Morus alba, 6 parts of Scutellaria baicalensis, 20 parts of raw oyster; or 30 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Morus alba, 6 parts of Scutellaria baicalensis, 30 parts of raw oyster; or 20 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Morus alba, 6 parts of Scutellaria baicalensis, 20 parts of raw oyster; or 30 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 30 parts of Leonurus japonicus, 10 parts of Gastrodia elata, 10 parts of Eucommia ulmoides, 15 parts of Morus alba, 9 parts of Scutellaria baicalensis, and 20 parts of raw oysters.

5. A Chinese medicine preparation for treating hypertensive heart failure, characterized in that: The Chinese medicine preparation uses the Chinese medicine composition according to any one of claims 1 to 4 as an active ingredient.

6. The Chinese medicine preparation according to claim 5, characterized in that: The traditional Chinese medicine preparation also contains pharmaceutically acceptable auxiliary materials.

7. The Chinese medicine preparation according to claim 5, characterized in that: The dosage form of the Chinese medicine preparation is decoction, granules, capsules, tablets, pills, granules or oral liquid.

8. The Chinese medicine preparation according to claim 7, characterized in that: The decoction is prepared according to the following steps: Weigh various Chinese medicinal materials according to the weight ratio of the raw materials, add 8-10 times of water to soak for 0.5-3h, boil over high heat first, then simmer over low heat to extract the juice, simmer for 1-2h, filter, collect the filtrate, add 8-10 times of water to the residue for a second decoction, filter, and combine the filtrates to obtain the product.

9. Use of the Chinese medicine composition according to any one of claims 1 to 4 or the Chinese medicine preparation according to any one of claims 5 to 8 in the preparation of a drug for treating hypertension and heart failure.

10. The use according to claim 9, characterized in that: The symptoms of hypertensive heart failure include preserved left ventricular ejection fraction.

Images