Application of a traditional Chinese medicine compound composition in preparing a drug for treating chest pain after coronary heart disease stent implantation

Abstract

The present invention discloses the use of a traditional Chinese medicine compound composition in preparing a drug for treating chest pain after coronary heart disease stent implantation, belonging to the technical field of traditional Chinese medicine. The traditional Chinese medicine compound composition comprises, by weight, 9-60 parts of peach kernel, 6-50 parts of safflower, 10-60 parts of gardenia, 15-90 parts of salvia miltiorrhiza, 10-60 parts of cyperus rotundus, 15-90 parts of millettia reticulata, 15-90 parts of angelica sinensis, 8-50 parts of ligusticum chuanxiong, 15-90 parts of red peony root, and 15-90 parts of codonopsis pilosula. The main components of the Chinese patent medicine include the volatile oil, alcohol extract, water extract and pharmaceutically acceptable excipients of the above-mentioned Chinese medicine compound composition, wherein the volatile oil is the volatile oil extracted from the Chinese medicine compound composition by steam distillation; the alcohol extract is the extract obtained by extracting the volatile oil from the Chinese medicine compound composition by steam distillation and then subjecting it to alcohol extraction treatment; the water extract is the extract obtained by extracting the volatile oil from the Chinese medicine compound composition by steam distillation and alcohol extraction treatment and then subjecting it to water extraction treatment.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a traditional Chinese medicine compound composition for treating chest pain after coronary heart disease stent implantation and a preparation method thereof. Background Art

[0002] Coronary revascularization, primarily including percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), is currently the mainstay of treatment for severe coronary artery disease. This approach can alleviate or eliminate coronary artery stenosis or occlusion, restore coronary blood flow, alleviate symptoms, and improve prognosis. However, 42% of PCI patients and 22% of CABG patients still experience varying degrees of persistent or recurrent chest pain despite standard Western medical therapy. The causes of post-PCI chest pain are complex, including coronary microcirculatory impairment, coronary artery spasm, incomplete revascularization, side branch occlusion, stent thrombosis, stent traction reaction, psychological factors, and other systemic comorbidities, presenting clinical challenges and challenges. Traditional Chinese medicine (TCM) has unique advantages in the syndrome differentiation treatment of post-PCI chest pain, effectively alleviating chest pain symptoms, improving patients' quality of life, and enhancing long-term prognosis. However, further research is needed to understand its pathogenesis and select appropriate prescriptions and medications.

[0003] In response to the above clinical difficulties, the inventors have proposed an innovative understanding of the pathogenesis of traditional Chinese medicine. Although the heart vessels are unblocked after PCI surgery, the interventional surgery mechanically dilates the blood vessels and implants stents to clear the stenosis, but at the same time, the endothelial tears and the damage to the small side vessels can be similar to the damage to the collateral vessels in traditional Chinese medicine, and are also similar to the wounds of the golden blade in traditional Chinese medicine theory. Moreover, as a chronic, low-grade vascular inflammatory disease, coronary heart disease only solves the main narrow blood vessels, and does not improve the complex microecological environment in the blood vessels. It is still easy to serve as a "soil" for the growth of thrombi, plaques, etc., leading to coronary microcirculation disorders, intra-stent thrombosis, intra-stent restenosis, etc., thereby causing chest pain. The microvascular inflammatory environment after coronary stent surgery can be understood from the perspective of the traditional Chinese medicine concept of hidden fire. Patients undergoing stent surgery are prone to anxiety and depression, which can generate fire in the heart and liver. The liver and kidney share the same origin, and in elderly patients, insufficient kidney water cannot contain wood, which can lead to internal heat and hidden fire. Over time, this weakened state can foster spleen deficiency and fire, as stated in the "Cangsheng Siming" (The Book of Destiny): "I have seen anger generate liver fire, worry generate lung fire, anxiety generate heart fire, fatigue generate spleen fire, and endless thoughts generate kidney fire." As this evil fire grows, it refines fluids to dissolve dampness, refines blood to generate blood stasis, and blocks blood vessels. This cycle repeats, creating a cycle of growth, consolidation, and finally tension, leading to frequent chest pain after revascularization surgery. Most patients with coronary artery disease are elderly and frail, with pre-existing heart and kidney deficiency. Traumatic surgery and stent implantation can deplete heart qi and disturb the mind. Furthermore, long-term oral use of antiplatelet drugs such as aspirin and clopidogrel after surgery can damage the spleen and stomach. The patient's own vascular conditions combined with surgical trauma lead to a mixture of "qi, fire, dampness and blood stasis", making the pathogenesis of chest pain after stent surgery complex and mixed, which is different from other types of angina pectoris.

[0004] For patients with angina pectoris characterized by heat, toxicity, and blood stasis after coronary revascularization surgery, the 2020 "Guidelines for the Integrated Diagnosis and Treatment of Angina Pectoris After Coronary Revascularization with Traditional Chinese and Western Medicine" recommends the use of Guanxin Formula II, which combines Chuanxiong, Paeonia lactiflora, Carthamus tinctorius, Dalbergia odorifera, and Salvia miltiorrhiza to promote blood circulation and dredge collaterals, with the addition of Coptis chinensis alone to clear heat and detoxify. For patients with prolonged disease progression, where qi deficiency and blood stasis develop, and stasis-induced heat develops, the guidelines recommend the use of a modified Qingxin Jieyu Formula, which combines raw Astragalus membranaceus to invigorate qi, Salvia miltiorrhiza and Chuanxiong to promote blood circulation, Patchouli odorifera to dissipate dampness, and Coptis chinensis to detoxify. These formulas all utilize mild blood-activating and stasis-removing herbs, relying on the combined use of similarly effective drugs for blood activation. This approach ignores the more severe vascular conditions found in patients undergoing coronary revascularization. Furthermore, these formulas focus solely on the underlying disease, failing to adhere to the TCM principle of the unity of form and spirit and addressing the "dual heart" condition. From the pre-operative notification of the severity of the patient's condition to the surgical plan, preoperative preparation, intraoperative procedures, and post-operative instructions, all aspects of coronary artery revascularization surgery can subtly affect the patient's seven emotions, thereby impacting Qi flow. This is particularly true during PCI, where the patient remains awake under local anesthesia, allowing for clear awareness of the entire procedure. Furthermore, after PCI, the passage of sharp instruments such as catheters, guidewires, balloons, and stents in and out of the coronary arteries (heart vessels) can, according to Traditional Chinese Medicine, disturb the mind, leading to Qi disturbances and mental disturbances.

[0005] The present invention proposes that the treatment of chest pain after stent surgery should be "treating both the heart and the meridians, regulating Qi, fire, dampness, and blood stasis." This approach aims to nourish the heart, which is weakened and suffering from blood stasis, calm the mind, which is disturbed and frightened, and regulate the harmony of the internal organs, body, and spirit. It proposes a treatment strategy of "clearing the heart and tonifying the kidney, calming the mind, invigorating Qi and activating blood circulation, removing blood stasis and unblocking the meridians, strengthening the spleen and warming the kidney, resolving phlegm and relieving numbness, soothing and nourishing the liver, regulating Qi and relieving chest tightness." The present invention's traditional Chinese medicine composition combines peach kernel with safflower to promote blood circulation and dispel blood stasis. Peach kernel, which is bitter and purgative, is effective in treating blood stasis in the internal organs, while safflower, which is pungent and warm, is effective in treating blood stasis in the meridians. Gardenia jasminoides, which is bitter and cold, enters the heart, lung, and triple burner meridians. When used raw, it enters the Qi component and is effective in clearing the fire of the heart and liver and relieving restlessness. Zhu Zhenheng stated that gardenia jasminoides "drain triple burner fire, clears blood in the stomach, treats heart pain caused by heat syncope, relieves heat and depression, and promotes the flow of Qi." Therefore, the three herbs are combined to complement each other. First, they can purge hidden fire in the meridians, focusing on improving vascular inflammation. Second, they treat both the heart and the mind simultaneously, addressing the underlying pathogenesis of fire. These two herbs serve as the main herbs. Salvia miltiorrhiza is bitter and slightly warm in nature, entering the heart and liver meridians. It has the effects of cooling blood, promoting blood circulation, relieving menstruation and pain, and clearing the heart and relieving restlessness. The "Ben Jing" states that it "treats evil qi in the heart and abdomen, rumbling bowels like running water, and accumulation of cold and heat; it dissolves tumors and masses, relieves restlessness and fullness, and replenishes qi." It complements peach kernel, safflower, and gardenia as auxiliary herbs. Cyperus rotundus is pungent, slightly bitter, slightly sweet, and neutral in flavor, entering the liver, spleen, and triple burner meridians, leveraging its effects of "regulating qi in the blood, relieving depression, soothing fullness, promoting digestion, and stopping vomiting." Chuanxiong and red peony root invigorate blood circulation and promote qi; Millettia reticulata and Chinese angelica invigorate and replenish blood circulation; and Codonopsis pilosula strengthens the spleen and replenishes qi, addressing the effects of anti-inflammatory drugs. The entire formula aims to address Qi, Fire, Dampness, and Stasis, harmonizing the heart, liver, and spleen, achieving the combined effects of clearing the heart, activating blood circulation, and soothing the liver and nourishing the heart. The addition of peach kernel and safflower enhances blood circulation and stasis removal. Gardenia clears the liver and purges fire, while Cyperus rotundus soothes liver qi and relieves depression. Codonopsis pilosula strengthens the spleen and stomach, preventing the bitter and cold effects of aspirin. This formula is more comprehensive and rational than other methods. Summary of the Invention

[0006] The purpose of the present invention is to provide a traditional Chinese medicine composition for treating chest pain after coronary heart disease stent implantation, a preparation method thereof and a traditional Chinese medicine, which solves the clinical treatment difficulties of chest pain after coronary heart disease stent implantation, has an auxiliary therapeutic effect on improving clinical symptoms such as chest pain and chest tightness after coronary heart disease stent implantation, and has the effects of clearing the heart, activating blood circulation, soothing the liver and nourishing the heart.

[0007] To achieve the above object, the present invention provides a traditional Chinese medicine composition for treating chest pain after coronary heart disease stent implantation, comprising, by weight, 9-60 parts of peach kernel, 6-50 parts of safflower, 10-60 parts of gardenia, 15-90 parts of salvia miltiorrhiza, 10-60 parts of cyperus rotundus, 15-90 parts of millettia reticulata, 15-90 parts of angelica sinensis, 8-50 parts of ligusticum chuanxiong, 15-90 parts of red peony root, and 15-90 parts of codonopsis pilosula.

[0008] The present invention also provides a Chinese medicinal ingredient composition for treating chest pain after coronary heart disease stent implantation, comprising: volatile oil extracted by steam distillation of the original Chinese medicinal compound composition slices; an alcohol extract, which is an extract obtained by subjecting the original Chinese medicinal compound composition slices to steam distillation to extract the volatile oil and then subjecting the original Chinese medicinal compound composition slices to alcohol extraction treatment; and a water extract, which is an extract obtained by subjecting the original Chinese medicinal compound composition slices to steam distillation to extract the volatile oil and then subjecting the original Chinese medicinal compound composition slices to alcohol extraction treatment and then subjecting the original Chinese medicinal compound composition slices to water extraction treatment.

[0009] The present invention also provides a preparation method of a traditional Chinese medicine composition for treating chest pain after coronary stent implantation. The alcohol extraction process comprises the following steps: using an ethanol solution with a volume concentration of 85% to 98% by volume as a first alcohol solution, performing a first alcohol extraction process on the medicinal residue after volatile oil extraction to obtain a first alcohol-extracted medicinal residue and a first alcohol extract; using an ethanol solution with a volume concentration of 65% to 85% by volume as a second alcohol solution, performing a second alcohol extraction process on the medicinal residue after the first alcohol extraction to obtain a second alcohol-extracted medicinal residue and a second alcohol extract; using an ethanol solution with a volume concentration of 45% to 65% by volume as a second alcohol solution, performing a second alcohol extraction process on the medicinal residue after the first alcohol extraction to obtain a second alcohol-extracted medicinal residue and a second alcohol extract. vt% ethanol solution as the third alcohol solution, performing a third alcohol extraction on the second alcohol-extracted medicinal residue to obtain a third alcohol-extracted medicinal residue and a third alcohol extract; during the three alcohol extractions, ethanol in an amount of 5-15 times the volume of the medicinal residue is added; each extraction takes 0.5-5 hours; the first alcohol extract, the second alcohol extract and the third alcohol extract are combined to obtain a mixed alcohol extract; the mixed alcohol extract is concentrated under reduced pressure at a temperature of 60-80°C and a vacuum degree of -0.07 to -0.09 MPa to obtain an alcohol-extracted clear paste; the alcohol-extracted clear paste has a relative density of 1.05-1.15 at 60°C.

[0010] The water extraction treatment comprises the following steps: using pure water to extract the medicinal residue after the third alcohol extraction twice, adding pure water in an amount 5-15 times the volume of the medicinal residue, and extracting for 0.5-5 hours each time to obtain a water extract; subjecting the water extract to alcohol precipitation treatment, taking the supernatant, and concentrating to obtain an alcohol-precipitated clear paste; the alcohol-precipitated clear paste has a relative density of 1.05-1.15 at 60°C.

[0011] The alcohol-extracted clear paste and the alcohol-precipitated clear paste are mixed and then dried to obtain extract powder.

[0012] The present invention also provides a Chinese patent medicine for treating chest pain after coronary stent implantation, characterized in that: the Chinese patent medicine is any one of tablets, granules, capsules, oral solutions, oral suspensions, oral dripping pills, and oral ointments; and / or each dosage unit of the Chinese patent medicine comprises 1.0 to 10.0 g of a pharmaceutical composition for treating chest pain after coronary stent implantation, wherein the Chinese patent medicine comprises an extract of the original Chinese herbal medicine slices.

[0013] The Chinese patent medicine is a dispersible tablet. In every 10,000 tablets, the Chinese medicine composition and main excipients include the following components in parts by weight: 1,000 to 2,000 parts by weight of the alcohol extract and water extract powder of the Chinese medicine composition, 3.0 to 6.0 parts by weight of the volatile oil of the Chinese medicine composition, 300 to 600 parts by weight of cross-linked polyvinyl pyrrolidone, 400 to 800 parts by weight of low-substituted hydroxypropyl cellulose, 300 to 600 parts by weight of sodium carboxymethyl starch, 800 to 1,600 parts by weight of erythritol, and 500 to 1,000 parts by weight of microcrystalline cellulose.

[0014] The present invention also provides a method for preparing a dispersible tablet of a Chinese patent medicine for treating chest pain after coronary stent implantation, characterized in that the method comprises the following steps: respectively grinding the extract powder of the alcohol extract and the water extract of the Chinese medicine composition and various auxiliary materials, and passing them through an 80-100 mesh sieve for standby use; uniformly mixing the extract powder of the Chinese medicine composition with the various auxiliary materials; using PEG4000 with a concentration of 30-40% as an adhesive, adding the volatile oil of the Chinese medicine composition, passing through a 20-80 mesh sieve for granulation, drying at 60°C, and then passing through a 20-80 mesh sieve for granulation, adding an appropriate amount of talc powder and magnesium stearate, mixing uniformly, and tableting to obtain the tablets.

[0015] Therefore, the present invention adopts the above-mentioned Chinese patent medicine for treating chest pain after coronary heart disease stent implantation and its preparation method, which solves the clinical treatment difficulties of chest pain after coronary heart disease stent implantation, has an auxiliary therapeutic effect on improving symptoms such as chest pain and chest tightness after coronary heart disease stent implantation, and has the effects of clearing the heart, activating blood circulation, soothing the liver and nourishing the heart.

[0016] The technical solution of the present invention is further described in detail below through examples. DETAILED DESCRIPTION

[0017] The technical solution of the present invention is further illustrated by the following examples.

[0018] Unless otherwise defined, technical or scientific terms used in the present invention shall have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs.

[0019] Example 1

[0020] A traditional Chinese medicine composition for treating chest pain after coronary heart disease stent implantation, comprising, by weight: 9 g peach kernel, 6 g safflower, 10 g gardenia, 15 g salvia miltiorrhiza, 10 g cyperus rotundus, 15 g millettia reticulata, 15 g angelica sinensis, 8 g ligusticum chuanxiong, 15 g red peony root, and 15 g codonopsis pilosula.

[0021] The preparation method comprises the following steps: weighing corresponding parts by weight of decoction pieces of peach kernel, safflower, gardenia, salvia miltiorrhiza, cyperus rotundus, millettia reticulata, angelica sinensis, ligusticum chuanxiong, red peony root, and codonopsis pilosula; steam distilling the raw medicinal pieces to extract volatile oil; extracting the medicinal residues with alcohol to obtain an alcohol extract; and extracting the medicinal residues with water to obtain a water extract.

[0022] The alcohol extraction process comprises the following steps: using an ethanol solution with a volume concentration of 85% to 98vt% as a first alcohol solution, performing a first alcohol extraction process on the medicinal residue after volatile oil extraction, to obtain a first alcohol-extracted medicinal residue and a first alcohol extract; using an ethanol solution with a volume concentration of 65% to 85vt% as a second alcohol solution, performing a second alcohol extraction process on the medicinal residue after the first alcohol extraction, to obtain a second alcohol-extracted medicinal residue and a second alcohol extract; using an ethanol solution with a volume concentration of 45% to 65vt% as a third alcohol solution, The medicinal residue after the second alcohol extraction is subjected to a third alcohol extraction treatment to obtain the medicinal residue after the third alcohol extraction and a third alcohol extract; during the three alcohol extraction processes, ethanol in an amount of 5-15 times the volume of the medicinal residue is added; each extraction takes 0.5-5 hours; the first alcohol extract, the second alcohol extract and the third alcohol extract are combined to obtain a mixed alcohol extract; the mixed alcohol extract is concentrated under reduced pressure at a temperature of 60-80°C and a vacuum degree of -0.07 to -0.09 MPa to obtain an alcohol-extracted clear paste; the alcohol-extracted clear paste has a relative density of 1.05-1.15 at 60°C.

[0023] The water extraction treatment comprises the following steps: using pure water to extract the medicinal residue after the third alcohol extraction twice, adding pure water in an amount 5-15 times the volume of the medicinal residue, and extracting for 0.5-5 hours each time to obtain a water extract; subjecting the water extract to alcohol precipitation treatment, taking the supernatant, and concentrating to obtain an alcohol-precipitated clear paste; the alcohol-precipitated clear paste has a relative density of 1.05-1.15 at 60°C.

[0024] The alcohol-extracted clear paste and the alcohol-precipitated clear paste are mixed and then dried to obtain extract powder.

[0025] Example 2

[0026] A traditional Chinese medicine composition for treating chest pain after coronary heart disease stent implantation, comprising, by weight: 60 g of peach kernel, 50 g of safflower, 60 g of gardenia, 90 g of salvia miltiorrhiza, 60 g of cyperus rotundus, 90 g of millettia reticulata, 90 g of angelica sinensis, 50 g of ligusticum chuanxiong, 90 g of red peony root, and 90 g of codonopsis pilosula.

[0027] The preparation method comprises the following steps: weighing corresponding parts by weight of decoction pieces of peach kernel, safflower, gardenia, salvia miltiorrhiza, cyperus rotundus, millettia reticulata, angelica sinensis, ligusticum chuanxiong, red peony root, and codonopsis pilosula; steam distilling the raw medicinal pieces to extract volatile oil; extracting the medicinal residues with alcohol to obtain an alcohol extract; and extracting the medicinal residues with water to obtain a water extract.

[0028] The alcohol extraction process comprises the following steps: using an ethanol solution with a volume concentration of 85% to 98vt% as a first alcohol solution, performing a first alcohol extraction process on the medicinal residue after volatile oil extraction, to obtain a first alcohol-extracted medicinal residue and a first alcohol extract; using an ethanol solution with a volume concentration of 65% to 85vt% as a second alcohol solution, performing a second alcohol extraction process on the medicinal residue after the first alcohol extraction, to obtain a second alcohol-extracted medicinal residue and a second alcohol extract; using an ethanol solution with a volume concentration of 45% to 65vt% as a third alcohol solution, The medicinal residue after the second alcohol extraction is subjected to a third alcohol extraction treatment to obtain the medicinal residue after the third alcohol extraction and a third alcohol extract; during the three alcohol extraction processes, ethanol in an amount of 5-15 times the volume of the medicinal residue is added; each extraction takes 0.5-5 hours; the first alcohol extract, the second alcohol extract and the third alcohol extract are combined to obtain a mixed alcohol extract; the mixed alcohol extract is concentrated under reduced pressure at a temperature of 60-80°C and a vacuum degree of -0.07 to -0.09 MPa to obtain an alcohol-extracted clear paste; the alcohol-extracted clear paste has a relative density of 1.05-1.15 at 60°C.

[0029] The water extraction treatment comprises the following steps: using pure water to extract the medicinal residue after the third alcohol extraction twice, adding pure water in an amount 5-15 times the volume of the medicinal residue, and extracting for 0.5-5 hours each time to obtain a water extract; subjecting the water extract to alcohol precipitation treatment, taking the supernatant, and concentrating to obtain an alcohol-precipitated clear paste; the alcohol-precipitated clear paste has a relative density of 1.05-1.15 at 60°C.

[0030] The alcohol-extracted clear paste and the alcohol-precipitated clear paste are mixed and then dried to obtain extract powder.

[0031] Example 3

[0032] A dispersible tablet Chinese patent medicine of a traditional Chinese medicine composition for treating chest pain after coronary stent implantation. The composition comprises, by weight, 900 g of peach kernel, 600 g of safflower, 1000 g of gardenia, 1500 g of salvia miltiorrhiza, 1000 g of cyperus rotundus, 1500 g of millettia reticulata, 1500 g of angelica sinensis, 800 g of ligusticum chuanxiong, 1500 g of red peony root, and 1500 g of codonopsis pilosula.

[0033] The Chinese medicine composition dispersible tablets, in every 10,000 tablets, the Chinese medicine composition and main excipients include the following components in parts by weight: 2,000 g of the alcohol extract and water extract powder of the Chinese medicine composition, 6 g of the volatile oil of the Chinese medicine composition, 600 g of cross-linked polyvinyl pyrrolidone, 800 g of low-substituted hydroxypropyl cellulose, 600 g of sodium carboxymethyl starch, 1,600 g of erythritol, and 1,000 g of microcrystalline cellulose.

[0034] The method for preparing the dispersible tablets of the Chinese medicine composition comprises the following steps:

[0035] Weigh the corresponding parts by weight of peach kernel, safflower, gardenia, salvia miltiorrhiza, cyperus rotundus, millettia reticulata, angelica sinensis, ligusticum chuanxiong, red peony root, and codonopsis pilosula. Steam distill the raw medicinal pieces to extract volatile oil; the medicinal residue is then subjected to alcohol extraction to obtain an alcohol extract; and the medicinal residue after alcohol extraction is further subjected to water extraction to obtain a water extract.

[0036] The alcohol extraction process comprises the following steps: using an ethanol solution with a volume concentration of 85% to 98vt% as a first alcohol solution, performing a first alcohol extraction process on the medicinal residue after volatile oil extraction, to obtain a first alcohol-extracted medicinal residue and a first alcohol extract; using an ethanol solution with a volume concentration of 65% to 85vt% as a second alcohol solution, performing a second alcohol extraction process on the medicinal residue after the first alcohol extraction, to obtain a second alcohol-extracted medicinal residue and a second alcohol extract; using an ethanol solution with a volume concentration of 45% to 65vt% as a third alcohol solution, The medicinal residue after the second alcohol extraction is subjected to a third alcohol extraction treatment to obtain the medicinal residue after the third alcohol extraction and a third alcohol extract; during the three alcohol extraction processes, ethanol in an amount of 5-15 times the volume of the medicinal residue is added; each extraction takes 0.5-5 hours; the first alcohol extract, the second alcohol extract and the third alcohol extract are combined to obtain a mixed alcohol extract; the mixed alcohol extract is concentrated under reduced pressure at a temperature of 60-80°C and a vacuum degree of -0.07 to -0.09 MPa to obtain an alcohol-extracted clear paste; the alcohol-extracted clear paste has a relative density of 1.05-1.15 at 60°C.

[0037] The water extraction treatment comprises the following steps: using pure water to extract the medicinal residue after the third alcohol extraction twice, adding pure water in an amount 5-15 times the volume of the medicinal residue, and extracting for 0.5-5 hours each time to obtain a water extract; subjecting the water extract to alcohol precipitation treatment, taking the supernatant, and concentrating to obtain an alcohol-precipitated clear paste; the alcohol-precipitated clear paste has a relative density of 1.05-1.15 at 60°C.

[0038] The alcohol-extracted clear paste and the alcohol-precipitated clear paste are mixed and then dried to obtain extract powder.

[0039] The alcohol extract and water extract powder of the traditional Chinese medicine composition and various auxiliary materials are ground respectively, passed through an 80-100 mesh sieve for later use; the extract powder of the traditional Chinese medicine composition and the various auxiliary materials are evenly mixed; PEG4000 with a concentration of 30-40% is used as an adhesive, and the volatile oil of the traditional Chinese medicine composition is added, and the mixture is passed through a 20-80 mesh sieve to prepare granules, dried at 60°C, and then passed through a 20-80 mesh sieve to prepare granules, and an appropriate amount of talc powder and magnesium stearate are added, mixed evenly, and tableted.

[0040] Example 4

[0041] A dispersible tablet Chinese patent medicine of a traditional Chinese medicine composition for treating chest pain after coronary stent implantation. The composition comprises, by weight, 6000 g of peach kernel, 5000 g of safflower, 6000 g of gardenia, 9000 g of salvia miltiorrhiza, 6000 g of cyperus rotundus, 9000 g of millettia reticulata, 9000 g of angelica sinensis, 5000 g of ligusticum chuanxiong, 9000 g of red peony root, and 9000 g of codonopsis pilosula.

[0042] The Chinese medicine composition dispersible tablets, in every 10,000 tablets, the Chinese medicine composition and main excipients include the following components in parts by weight: 4,000 g of the alcohol extract and water extract powder of the Chinese medicine composition, 12 g of the volatile oil of the Chinese medicine composition, 1,200 g of cross-linked polyvinyl pyrrolidone, 1,600 g of low-substituted hydroxypropyl cellulose, 1,200 g of sodium carboxymethyl starch, 3,200 g of erythritol, and 2,000 g of microcrystalline cellulose.

[0043] The method for preparing the dispersible tablets of the Chinese medicine composition comprises the following steps:

[0044] Weigh the corresponding parts by weight of peach kernel, safflower, gardenia, salvia miltiorrhiza, cyperus rotundus, millettia reticulata, angelica sinensis, ligusticum chuanxiong, red peony root, and codonopsis pilosula. Steam distill the raw medicinal pieces to extract volatile oil; the medicinal residue is then subjected to alcohol extraction to obtain an alcohol extract; and the medicinal residue after alcohol extraction is further subjected to water extraction to obtain a water extract.

[0045] The alcohol extraction process comprises the following steps: using an ethanol solution with a volume concentration of 85% to 98vt% as a first alcohol solution, performing a first alcohol extraction process on the medicinal residue after volatile oil extraction, to obtain a first alcohol-extracted medicinal residue and a first alcohol extract; using an ethanol solution with a volume concentration of 65% to 85vt% as a second alcohol solution, performing a second alcohol extraction process on the medicinal residue after the first alcohol extraction, to obtain a second alcohol-extracted medicinal residue and a second alcohol extract; using an ethanol solution with a volume concentration of 45% to 65vt% as a third alcohol solution, The medicinal residue after the second alcohol extraction is subjected to a third alcohol extraction treatment to obtain the medicinal residue after the third alcohol extraction and a third alcohol extract; during the three alcohol extraction processes, ethanol in an amount of 5-15 times the volume of the medicinal residue is added; each extraction takes 0.5-5 hours; the first alcohol extract, the second alcohol extract and the third alcohol extract are combined to obtain a mixed alcohol extract; the mixed alcohol extract is concentrated under reduced pressure at a temperature of 60-80°C and a vacuum degree of -0.07 to -0.09 MPa to obtain an alcohol-extracted clear paste; the alcohol-extracted clear paste has a relative density of 1.05-1.15 at 60°C.

[0046] The water extraction treatment comprises the following steps: using pure water to extract the medicinal residue after the third alcohol extraction twice, adding pure water in an amount 5-15 times the volume of the medicinal residue, and extracting for 0.5-5 hours each time to obtain a water extract; subjecting the water extract to alcohol precipitation treatment, taking the supernatant, and concentrating to obtain an alcohol-precipitated clear paste; the alcohol-precipitated clear paste has a relative density of 1.05-1.15 at 60°C.

[0047] The alcohol-extracted clear paste and the alcohol-precipitated clear paste are mixed and then dried to obtain extract powder.

[0048] The alcohol extract and water extract powder of the traditional Chinese medicine composition and various auxiliary materials are ground respectively, passed through an 80-100 mesh sieve for later use; the extract powder of the traditional Chinese medicine composition and the various auxiliary materials are evenly mixed; PEG4000 with a concentration of 30-40% is used as an adhesive, and the volatile oil of the traditional Chinese medicine composition is added, and the mixture is passed through a 20-80 mesh sieve to prepare granules, dried at 60°C, and then passed through a 20-80 mesh sieve to prepare granules, and an appropriate amount of talc powder and magnesium stearate are added, mixed evenly, and tableted.

[0049] Effect Example 1

[0050] The alcohol-extracted clear paste, alcohol-precipitated clear paste and volatile oil in Example 1 were mixed to prepare a Chinese medicine composition ointment, and the therapeutic effect of the Chinese medicine composition of the present invention for treating chest pain after coronary heart disease stent implantation was demonstrated through clinical trials.

[0051] (1) Case sources and grouping

[0052] All cases were recruited from inpatients and outpatients admitted to the Cardiology Department of Jiangsu Provincial Hospital of Integrated Traditional Chinese and Western Medicine between March 2021 and August 2023. All enrolled patients had a diagnosis of coronary artery disease and had undergone PCI or CABG. They also had persistent chest pain or tightness after surgery, and had undergone relevant examinations to exclude severe ischemia or other organic diseases. Traditional Chinese Medicine diagnosis of toxic heat and blood stasis was performed. Enrolled patients were randomly divided into a control group (n=30) and an experimental group (n=30) using a random number table.

[0053] (2) Treatment methods

[0054] Both groups of patients were routinely treated with standard medications, including aspirin, clopidogrel, and statins, according to relevant guidelines and following a Western medicine medication regimen for secondary prevention of coronary heart disease after revascularization. The experimental group was given the traditional Chinese medicine ointment of Example 1, 20 ml each time, twice daily, with 50 ml of warm water, in addition to conventional treatment.

[0055] (3) Observation indicators and efficacy standards

[0056] With reference to the "Standards for Diagnosis and Efficacy of Traditional Chinese Medicine Diseases and Syndromes" promulgated by the State Administration of Traditional Chinese Medicine, the TCM syndrome scale was used to score the patient's syndromes before and after treatment (0-10 points).

[0057] The "efficacy index" was used as the evaluation criterion based on the patient's subjective assessment of their symptom severity. The efficacy index = [(pre-treatment score - post-treatment score) / pre-treatment score] × 100%. Marked efficacy: symptoms essentially disappeared or completely disappeared after treatment, with an efficacy index greater than 70%; effective: symptoms were alleviated or improved after treatment, with an efficacy index of 30%-70%; ineffective: symptoms did not alleviate or even worsened after treatment, with an efficacy index less than 30%.

[0058] The patients were evaluated on the basis of their subjective awareness of the severity of their own symptoms, and the "chest pain score" was selected as the evaluation standard: 0 points: no chest pain; 2 points: mild chest pain, with a self-rated pain score of 1 to 3 points; 4 points: obvious chest pain, with a self-rated pain score of 4 to 6 points; 6 points: severe chest pain, with a self-rated pain score of 7 to 10 points.

[0059] SAS scale: It adopts a 4-level scoring method and is divided into four levels, namely 1, 2, 3, and 4. The main statistical indicator is the standard score. The standard score = the score of each item × 1.25, and the integer part is taken. If the SAS standard score is ≥50 points, it is considered to be in an anxious state.

[0060] After 4 weeks of treatment, follow-up was conducted to record the number of times the two groups of patients visited the doctor again due to chest pain symptoms.

[0061] Results and Analysis

[0062] SPSS statistical analysis software was used for analysis, and measurement data were expressed as mean ± standard deviation. Baseline data were tested for homogeneity of variance, while unequal variances were tested using the rank sum test. Count data were tested using the chi-square test. Measurement data between two groups were compared using the two-sample t-test, and measurement data between multiple groups were analyzed using one-way analysis of variance. P < 0.05 was considered statistically significant.

[0063] (1) Comparison of clinical efficacy between the two groups

[0064] The markedly effective rate and effective rate of the experimental group were higher than those of the control group, and the total effective rate of the experimental group was significantly higher than that of the control group, with significant statistical differences (P < 0.01). See Table 1:

[0065] Table 1 Comparison of clinical efficacy between the two groups, n (%)

[0066] Group n Significant effect efficient invalid Total effective rate / % control group 30 13（43.3） 3（10） 14（46.7） 53.3 experimental group 30 16（53.3） 9（30） 5（16.7） 83.3*

[0067] Note: *Compared with the control group, P < 0.01.

[0068] (2) Comparison of chest pain scores before and after treatment between the two groups

[0069] After treatment, the scores of the experimental group were lower than those of the control group, and the difference was statistically significant (P < 0.01). See Table 2:

[0070] Table 2 Comparison of chest pain scores before and after treatment in the two groups of patients ( )

[0071] Group n Before treatment After treatment control group 30 16.14 ± 5.63 13.87 ± 6.09 experimental group 30 15.89 ± 6.27 6.44 ± 2.15*

[0072] Note: *Compared with the control group after treatment, P < 0.01.

[0073] (3) Comparison of SAS scores between the two groups before and after treatment

[0074] After treatment, the SAS score of the experimental group was significantly lower than that of the control group, and the difference was statistically significant (P < 0.01). See Table 3:

[0075] Table 3 Comparison of SAS scores before and after treatment between the two groups of patients ( )

[0076] Group n Before treatment After treatment control group 30 53.82 ± 6.13 51.74 ± 3.88 experimental group 30 54.27 ± 4.90 40.08 ± 5.47*

[0077] Note: *Compared with the control group after treatment, P < 0.01.

[0078] (4) Comparison of the number of re-visits due to chest pain between the two groups after treatment

[0079] The number of re-visits in the experimental group was significantly lower than that in the control group, and the re-visit rate in the experimental group was significantly lower than that in the control group. See Table 4:

[0080] surface Comparison of the number of re-visits due to chest pain between the two groups after treatment

[0081] Group n Number of re-visits (times) Readmission rate (%) control group 30 27 90.0% experimental group 30 11 36.7*

[0082] Note: *Compared with the control group, P < 0.01.

[0083] Effect Example 2

[0084] The alcohol-extracted clear paste, alcohol-precipitated clear paste and volatile oil in Example 1 were mixed to prepare a Chinese medicine composition ointment. The therapeutic effect of the Chinese medicine composition of the present invention for treating chest pain after coronary heart disease stent implantation was illustrated through specific effective cases.

[0085] A 42-year-old male patient presented with recurrent chest pain for over a year. He had suffered from chronic conditions such as hypertension, diabetes, and hyperlipidemia for over a decade. Recurrent chest pain began a year ago, and coronary angiography revealed 75% localized stenosis in the mid-segment of the left anterior descending coronary artery and 80% diffuse stenosis in the mid-distal segment of the right coronary artery. Three stents were implanted in these two lesions. Postoperatively, he continued to experience recurrent chest tightness, pain, and shortness of breath. Despite adequate use of dual antiplatelet drugs, statins, coronary nitrates, beta-blockers to reduce myocardial oxygen consumption, trimetazidine, and nicorandil, his symptoms showed little improvement. Current diagnosis: chest pain and chest tightness occur from time to time, especially in the ribs, with occasional palpitations, easy to be frightened, always afraid that the stent will "fall off", shortness of breath and fatigue, like to lie down, sleep more, pharyngeal discomfort in the morning, like to clear the throat, sputum, dry mouth and bitter taste, abdominal distension and belching after eating, frequent urination at night, sticky stool, poor sleep at night, dark red tongue, fat tongue with teeth marks on the edges, yellow greasy tongue coating, thready pulse. Western medicine diagnosis: coronary heart disease stent implantation status, type 2 diabetes, hypertension; Chinese medicine diagnosis: chest pain and heart pain, the card belongs to blood stasis and heat disturbing the heart, liver depression and spleen deficiency. Intended method of clearing the heart and activating blood circulation, soothing the liver and nourishing the heart. Give and take the Chinese medicine composition ointment in Example 1, each 20ml, twice a day, 50ml of warm water.

[0086] Second diagnosis: After taking the medicine for 2 weeks, the patient showed that chest tightness, shortness of breath, and palpitations were significantly relieved, the number of chest pains was significantly reduced, fatigue, dry mouth, bitter taste in the mouth, abdominal distension and belching were all improved to varying degrees, but the patient still had poor sleep and sticky stools, yellow greasy tongue coating, and a thin and rapid pulse. The patient continued to take the Chinese medicine composition ointment in Example 1.

[0087] Third visit: After taking the medicine for 4 weeks, all symptoms were significantly improved. Chest pain basically stopped, insomnia improved, appetite and bowel movements basically returned to normal, tongue was pale red, swollen with teeth marks on the edges, tongue coating was thin white, and pulse was thready.

[0088] Therefore, the present invention adopts the above-mentioned traditional Chinese medicine composition for treating chest pain after coronary heart disease stent implantation and its preparation method, which solves the clinical prevention and treatment difficulties of chest pain after coronary heart disease stent implantation, has an auxiliary therapeutic effect on improving symptoms such as chest pain and chest tightness, and has the effects of clearing the heart, activating blood circulation, soothing the liver and nourishing the heart.

[0089] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit the same. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that they can still modify or replace the technical solutions of the present invention with equivalents, and these modifications or equivalent replacements cannot cause the modified technical solutions to deviate from the gist and scope of the technical solutions of the present invention.

Claims

1. Use of a Chinese medicine compound composition in the preparation of a drug for treating chest pain after coronary stent implantation, characterized in that The traditional Chinese medicine compound composition is prepared from the following raw materials in parts by mass: 9-60 parts of peach kernel, 6-50 parts of safflower, 10-60 parts of gardenia, 15-90 parts of salvia miltiorrhiza, 10-60 parts of cyperus rotundus, 15-90 parts of millettia reticulata, 15-90 parts of angelica sinensis, 8-50 parts of ligusticum chuanxiong, 15-90 parts of red peony root, and 15-90 parts of codonopsis pilosula.

2. Use of a Chinese medicine compound composition according to claim 1 in preparing a drug for treating chest pain after coronary stent implantation, characterized in that: The preparation method comprises the following steps: performing volatile oil extraction on Chinese herbal medicine slices including salvia miltiorrhiza, gardenia jasminoides, cyperus rotundus, millettia reticulata, codonopsis pilosula, ligusticum chuanxiong, red peony root, peach kernel, safflower and angelica sinensis to obtain medicinal residues and volatile oil; performing alcohol extraction on the medicinal residues three times with alcohol solutions of different concentrations to obtain alcohol extracts and alcohol-extracted medicinal residues; and performing water extraction on the alcohol-extracted medicinal residues with purified water to obtain a water extract.

3. Use of a Chinese medicine compound composition according to claim 2 in preparing a drug for treating chest pain after coronary stent implantation, characterized in that: include: The volatile oil obtained according to claim 2 is the volatile oil extracted by steam distillation of the original medicinal material of the Chinese medicine compound composition; The alcohol extract is an extract obtained by subjecting the original medicine of the Chinese herbal compound composition to the steam distillation to extract the volatile oil, and then subjecting it to alcohol extraction treatment; the water extract is an extract obtained by subjecting the original medicine of the Chinese herbal compound composition to the steam distillation to extract the volatile oil and the alcohol extraction treatment, and then subjecting it to water extraction treatment.

4. Use of a Chinese medicine compound composition according to claim 3 in preparing a drug for treating chest pain after coronary stent implantation, characterized in that: The alcohol extraction process comprises the following steps: Using an ethanol solution with a volume concentration of 85% to 98vt% as a first alcohol solution, performing a first alcohol extraction process on the medicinal residue after the volatile oil is extracted to obtain the first alcohol-extracted medicinal residue and a first alcohol extract; Using an ethanol solution with a volume concentration of 65% to 85vt% as a second alcohol solution, performing a second alcohol extraction process on the medicinal residue after the first alcohol extraction to obtain the medicinal residue after the second alcohol extraction and the second alcohol extract; Using an ethanol solution with a volume concentration of 45% to 65vt% as a third alcohol solution, performing a third alcohol extraction treatment on the second alcohol-extracted medicinal residue to obtain a third alcohol-extracted medicinal residue and a third alcohol extract; During the three alcohol extractions, 5-15 times the volume of the medicinal residue was added with ethanol; each extraction took 0.5-5 hours; combining the first alcohol extract, the second alcohol extract, and the third alcohol extract to obtain a mixed alcohol extract; The mixed alcohol extract is concentrated under reduced pressure at a temperature of 60 to 80° C. and a vacuum degree of -0.07 to -0.09 MPa to obtain an alcohol-extracted clear paste; The relative density of the alcohol-extracted clear paste at 60° C. is 1.05-1.

15.

5. Use of a Chinese medicine compound composition according to any one of claims 3 to 4 in preparing a drug for treating chest pain after coronary stent implantation, characterized in that: The water extraction process comprises the following steps: Extracting the medicinal residue after the third alcohol extraction twice with purified water, adding 5-15 times the volume of the medicinal residue with purified water, each extraction time for 0.5-5 hours, to obtain a water extract; The aqueous extract is subjected to alcohol precipitation treatment, and the supernatant is collected and concentrated to obtain an alcohol-precipitated clear paste; The relative density of the alcohol precipitation paste at 60° C. is 1.05-1.

15.

6. Use of a Chinese medicine compound composition according to any one of claims 3 to 5 in the preparation of a drug for treating chest pain after coronary stent implantation, wherein the compound further comprises: The alcohol-extracted clear paste and the alcohol-precipitated clear paste are mixed and then dried to obtain extract powder.

7. Use of a Chinese medicine compound composition according to claim 6 in preparing a drug for treating chest pain after coronary stent implantation, characterized in that: The Chinese patent medicine comprises a Chinese medicine composition and pharmaceutically acceptable excipients.

8. Use of a Chinese medicine compound composition according to claim 7 in preparing a drug for treating chest pain after coronary stent implantation, characterized in that: The Chinese patent medicine is any one of tablets, granules, capsules, oral solutions, oral suspensions, oral pills, and oral ointments; and / or each dosage unit of the Chinese patent medicine includes 1.0 to 10.0 g of a pharmaceutical composition for treating chest pain after coronary heart disease stent implantation, which is extracted from the original Chinese herbal medicine slices.

9. Use of a Chinese medicine compound composition according to claim 8 in preparing a drug for treating chest pain after coronary stent implantation, characterized in that: The Chinese patent medicine is a dispersible tablet. In every 10,000 tablets, the Chinese medicine composition and main excipients are prepared according to the following mass parts: 1000-2000 parts by weight of the alcohol extract and water extract powder of the traditional Chinese medicine composition, 3.0-6.0 parts by weight of the volatile oil of the traditional Chinese medicine composition, 300-600 parts by weight of cross-linked polyvinyl pyrrolidone, 400-800 parts by weight of low-substituted hydroxypropyl cellulose, 300-600 parts by weight of sodium carboxymethyl starch, 800-1600 parts by weight of erythritol, and 500-1000 parts by weight of microcrystalline cellulose; 10. Use of a Chinese medicine compound composition according to claims 1-9 in preparing a drug for treating chest pain after coronary stent implantation, characterized in that The method comprises the following steps: Grind the alcohol extract and water extract powder of the Chinese medicine composition and various auxiliary materials respectively, and pass them through an 80-100 mesh sieve for later use; Evenly mixing the extract powder of the Chinese medicine composition with various auxiliary materials; PEG4000 with a concentration of 30-40% is used as an adhesive, and volatile oil of the traditional Chinese medicine composition is added. The mixture is sieved through a 20-80 mesh sieve to form granules, dried at 60°C, and then sieved through a 20-80 mesh sieve to refine the granules. Appropriate amounts of talc powder and magnesium stearate are added, mixed evenly, and tableted.