A traditional Chinese medicine composition for treating chronic heart failure

Abstract

The application provides a traditional Chinese medicine composition for treating chronic heart failure, comprising 20-110 parts of ginseng, 5-25 parts of money grass, 8-60 parts of tuckahoe, 5-60 parts of ophiopogon, 5-30 parts of dragon bone and 0.5-5 parts of cinnabar. The traditional Chinese medicine drugs are combined to produce synergistic effect of the drugs, and the traditional Chinese medicine composition has the effects of tonifying qi and detoxifying, promoting blood circulation and removing water, tonifying qi and warming yang, nourishing yin and promoting blood circulation, calming heart and tranquilizing mind, and has a remarkable effect on heart failure. It is proved that the traditional Chinese medicine composition has a remarkable effect of improving heart function on a rat model with chronic heart failure, can obviously improve left ventricular ejection fraction, and can obviously improve left ventricular systolic pressure, left ventricular diastolic pressure, left ventricular systolic maximum rate, left ventricular diastolic maximum rate and the like, and has a clinical application prospect. In addition, the preparation method of the composition is simple in steps and is beneficial to industrial production.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a traditional Chinese medicine composition for treating chronic heart failure. Background Technology

[0002] Chronic heart failure is a heart disease caused by chronic heart disease and long-term ventricular overload, leading to reduced myocardial contractility, difficulty in cardiac blood ejection, venous congestion, and decreased arterial stroke volume, which cannot meet the metabolic needs of tissues. The incidence and mortality of chronic heart failure are on the rise, with late-stage mortality rates comparable to cancer. The resulting medical costs and social burden are also rapidly increasing. Current Western medicine guidelines for the treatment of chronic heart failure mainly rely on the "golden triangle" approach, including ACE inhibitors, beta-blockers, and aldosterone receptor antagonists. While Western medicine has certain advantages and effects in treating chronic heart failure, it also has limitations. For example, in elderly heart failure patients with normal left ventricular ejection fraction, beta-blockers do not reduce mortality and / or readmission rates; in hemodynamically unstable patients, intravenous beta-blockers increase the risk of cardiogenic shock and mortality. ACE inhibitors can cause irritating dry cough and potentially fatal laryngeal edema. The use of the aldosterone antagonist spironolactone can lead to hyperkalemia, gynecomastia in men, and decreased sexual function. In addition, heart failure is a chronic disease, and long-term medication can easily lead to drug resistance and cause low blood pressure, cough, water and electrolyte imbalance, which can affect the treatment effect.

[0003] In the field of Traditional Chinese Medicine (TCM), chronic heart failure falls under the category of "heart failure disease." TCM believes that the main pathogenesis of chronic heart failure includes qi deficiency, blood stasis, water retention, and yang deficiency. Treatment primarily focuses on tonifying qi, promoting blood circulation, eliminating water retention, and replenishing yang. TCM has certain advantages in treating chronic heart failure. Through TCM syndrome differentiation and treatment, it can alleviate patient symptoms, improve quality of life, and reduce the readmission rate. Furthermore, TCM has fewer side effects, lower costs, better patient compliance, and more significant efficacy, and allows for easy adjustment of medication regimens. Summary of the Invention

[0004] Based on long-term clinical observation and combined with modern medical understanding of the pathophysiological mechanisms of heart failure and the development trends of medical concepts, the inventors believe that congestive heart failure has a long course, is protracted and difficult to cure, often resulting in yin deficiency due to yang deficiency, and vice versa, leading to a deficiency of both yin and yang, and a complex condition. The pathogenesis may include manifestations of qi deficiency, yang deficiency, yin deficiency, blood stasis, and toxic pathogens. Based on this, the inventors have formulated a treatment for heart failure based on tonifying qi and detoxifying, promoting blood circulation and diuresis, tonifying qi and warming yang, nourishing yin and promoting blood circulation, and calming the mind and spirit. Animal experiments have verified that the treatment has achieved good results, and the formula will be used clinically in the future.

[0005] This invention provides a traditional Chinese medicine composition for treating chronic heart failure, the composition comprising the following active ingredients:

[0006] Ginseng 20-110 parts, Lysimachia christinae 5-25 parts, Poria cocos 8-60 parts, Ophiopogon japonicus 5-60 parts, Dragon bone 5-30 parts, Cinnabar 0.5-5 parts.

[0007] Preferably, the composition comprises the following active ingredients: 50 parts ginseng, 12 parts Lysimachia christinae, 30 parts Poria cocos, 15 parts Ophiopogon japonicus, 10 parts dragon bone, and 2 parts cinnabar.

[0008] This invention also provides a method for preparing a traditional Chinese medicine composition for treating chronic heart failure, comprising:

[0009] Take all the herbs except cinnabar, decoct them in water 1-3 times, each time for 1-3 hours, combine the decoctions, and let stand for 24-48 hours. Filter, concentrate the filtrate to a relative density of 1.1-1.4, dry, pulverize, add cinnabar, mix well, and package.

[0010] Preferably, the cinnabar is water-milled, and then the remaining herbs are decocted three times with five times the amount of water, each time for two hours. The decoctions are combined and left to stand for 24 hours. The filtrate is filtered, concentrated to a relative density of 1.19-1.25, dried, pulverized, and mixed with the water-milled cinnabar. The mixture is then packaged.

[0011] The present invention also provides the use of a traditional Chinese medicine composition in the preparation of a drug for treating chronic heart failure.

[0012] Preferably, the drug further includes pharmaceutically acceptable excipients, including excipients for liquid formulations, semi-solid formulations, solid formulations, transdermal formulations, and spray formulations.

[0013] Preferably, the excipients also include fillers, binders, disintegrants, lubricants, flow aids, wetting agents, effervescent agents, colorants, sweeteners, flavorings, preservatives, dispersants, film-forming agents, plasticizers, pore-forming agents, light-blocking agents, and retardants.

[0014] The pharmacological functions of each component in the traditional Chinese medicine composition of this invention are as follows:

[0015] Ginseng is a traditional Chinese medicine with a medicinal history of over 2000 years, known for its powerful tonic effects and ability to restore vitality and reverse collapse. Modern medicine indicates that ginseng has cardiotonic, vasodilatory, and antithrombotic effects, specifically: Ginseng has a significant cardiotonic effect because its saponins can enhance myocardial contractility, reduce myocardial oxygen consumption, slow heart rate, increase cardiac output and coronary blood flow, and combat arrhythmia. Ginseng can regulate blood vessels; different monomers of ginsenosides can cause vasodilation and vasoconstriction. Ginseng generally has a vasodilatory effect, but it does not have a significant effect on lowering blood pressure. Ginseng has anti-polymerization, anticoagulant, and antithrombotic effects. Ginsenosides reduce blood viscosity, lower erythrocyte sedimentation rate, and have antiplatelet aggregation, anticoagulant, and antithrombotic effects.

[0016] Lysimachia christinae, also known as Sichuan Lysimachia christinae, is a plant belonging to the genus Lysimachia in the family Primulaceae. It has a sweet and slightly bitter taste and is cool in nature. It enters the liver, gallbladder, kidney, and bladder meridians. Its main functions and indications include: promoting urination and relieving strangury; clearing heat and detoxifying; dispersing blood stasis and reducing swelling; treating liver, gallbladder, and urinary tract stones; treating urinary tract infections; treating nephritis edema; treating damp-heat jaundice; treating carbuncles and boils; treating snake bites; and treating traumatic injuries. Modern research shows that Lysimachia christinae contains various chemical components such as flavonoids, volatile oils, polysaccharides, and triterpenoid saponins, which have anti-ischemic and vasodilatory effects.

[0017] Ophiopogon japonicus, in its flavor and nature, is sweet, slightly bitter, and slightly cold. Its functions and indications include moistening the lungs and clearing the heart, nourishing the stomach and promoting fluid production, treating lung dryness damaging yin, yin deficiency with excessive fire, qi and yin deficiency, palpitations, and excessive sweating. Ophiopogon japonicus is a yin-nourishing herb. Traditional Chinese medicine believes it nourishes yin and promotes fluid production, moistens the lungs and relieves cough. It can be used to alleviate and treat symptoms such as spleen and stomach deficiency and cold, dry mouth and tongue, dry cough with hemoptysis, etc., and can also relieve palpitations caused by heart yin deficiency and dryness after febrile diseases. It is suitable for symptoms of internal heat disturbing the heart, febrile diseases with pathogenic heat entering the nutritive level, fever worse at night, restlessness, etc. It is also suitable for those with heat damaging qi and yin, irritability, thirst, sweating, and fatigue. It is also suitable for those with heart yin deficiency, irritability, insomnia, red tongue with little coating. Ophiopogon japonicus contains a large amount of alkaloids, sitosterol, amino acids, and vitamins, which have anti-fatigue, free radical scavenging, and blood sugar lowering effects. It also has sedative, hypnotic, anti-ischemic, arrhythmic, and anti-tumor effects, offering many health benefits.

[0018] Poria cocos is sweet and bland in taste, with a mild medicinal nature. It promotes diuresis and eliminates dampness; strengthens the spleen and stomach; calms the mind and soothes the nerves. It is mainly used for urinary difficulty; edema and abdominal distension; phlegm-dampness cough; vomiting; spleen deficiency with poor appetite; diarrhea; palpitations; insomnia and forgetfulness; seminal emission and leukorrhea. It is used for edema with scanty urine, phlegm-dampness dizziness and palpitations, spleen deficiency with poor appetite, loose stools and diarrhea, restlessness, palpitations, and insomnia. The main chemical components of Poria cocos include: polysaccharides (β-Poria cocos polysaccharide), triterpenoids, ergosterol, choline, adenine, amino acids, lecithin, etc. Modern experiments have shown that Poria cocos can significantly reduce spontaneous activity in mice; it has a significant synergistic effect with sedatives and anesthetics; Poria cocos polysaccharides can enhance the phagocytic capacity of peritoneal macrophages and promote humoral immunity in mice, increasing the number of white blood cells in the thymus, lymph nodes, and peripheral blood. Extracts and compound preparations of Poria cocos have significant diuretic effects.

[0019] Dragon bone is a fossilized skeleton of ancient large mammals such as elephants, three-toed horses, rhinoceroses, deer, and cattle. It has a sweet and astringent taste and is associated with the heart meridian, possessing a certain calming and sedative effect. It can be used to treat restlessness, palpitations, insomnia, epilepsy, and mania. Dragon bone is neutral in nature and is associated with the liver and kidney meridians. Its heavy and descending nature gives it a strong effect of calming the liver and suppressing yang, treating dizziness, irritability, and other symptoms caused by liver yang hyperactivity. Dragon bone has an astringent taste and astringent properties, treating seminal emission and spermatorrhea caused by kidney deficiency, frequent urination caused by deficiency of both heart and kidney, spontaneous sweating due to superficial deficiency, night sweats due to yin deficiency, and conditions such as damp sores, itchy rashes, and chronic, non-healing ulcers.

[0020] Cinnabar, a natural mineral, is both a sedative and a heat-clearing and detoxifying agent. It has a sweet taste and cold nature; its coldness helps to reduce internal heat, and it specifically enters the heart meridian. It can both calm the mind and soothe the nerves, making it suitable for various symptoms of mental restlessness. For insomnia, excessive dreaming, palpitations, and restlessness, it is often combined with Angelica sinensis, Rehmannia glutinosa, and Glycyrrhiza uralensis. For febrile diseases, high fever, irritability, delirium, convulsions, it is often combined with Calculus bovis and Musk. For mania caused by phlegm-fire, it is often combined with Iron filings, Asparagus cochinchinensis, and Ophiopogon japonicus. For infantile convulsions, it is often combined with Calculus bovis, Scorpion, and Uncaria rhynchophylla. For epilepsy with sudden fainting and convulsions, it is often combined with Magnetite. For childhood epilepsy, it is ground into a fine powder and made into pills with Realgar and Pearl for oral administration. Cinnabar is cold in nature and has heat-clearing and detoxifying effects; it can be used both internally and externally. For treating sores and boils, it is often combined with realgar, Cremastra appendiculata, and Euphorbia pekinensis; for treating sore throat and mouth ulcers, it is often combined with Glauber's salt.

[0021] This invention utilizes a combination of the aforementioned traditional Chinese medicines to achieve a synergistic effect, thereby invigorating qi and detoxifying, promoting blood circulation and diuresis, tonifying qi and warming yang, nourishing yin and promoting blood circulation, and calming the mind and spirit. It exhibits significant effects on heart failure. Evidence has shown that the traditional Chinese medicine composition of this invention significantly improves cardiac function in a rat model of chronic heart failure, not only significantly increasing left ventricular ejection fraction (LVEF), but also significantly improving left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), and maximum left ventricular systolic rate (+dp / dt). max ), maximum diastolic velocity of the left ventricle (-dp / dt) max These compositions have promising clinical applications. Furthermore, the preparation method of the compositions of this invention is simple and conducive to industrial production. Detailed Implementation

[0022] Example 1

[0023] Preparation of Traditional Chinese Medicine Compositions

[0024] Prescription composition: 50 parts ginseng, 12 parts Lysimachia christinae, 30 parts Poria cocos, 15 parts Ophiopogon japonicus, 10 parts dragon bone, and 2 parts cinnabar.

[0025] Preparation: Cinnabar is water-milled, then the remaining herbs are decocted three times with water, each time for 2 hours. The decoctions are combined and left to stand for 24 hours. The decoction is filtered, concentrated to a relative density of 1.19-1.25, dried, pulverized, and mixed with water and cinnabar. The mixture is then packaged.

[0026] Comparative Example 1

[0027] The preparation of the traditional Chinese medicine composition differs from Example 1 in that ginseng is replaced with danshen.

[0028] Prescription composition: 50 parts of Salvia miltiorrhiza, 12 parts of Lysimachia christinae, 30 parts of Poria cocos, 15 parts of Ophiopogon japonicus, 10 parts of dragon bone, and 2 parts of cinnabar.

[0029] Preparation: Cinnabar is water-milled, then the remaining herbs are decocted three times with water, each time for 2 hours. The decoctions are combined and left to stand for 24 hours. The filtrate is filtered, concentrated to a relative density of 1.19-1.25, dried, pulverized, and mixed with the water-milled cinnabar. The mixture is then packaged.

[0030] Comparative Example 2

[0031] The preparation of the traditional Chinese medicine composition differs from Example 1 in that cinnabar is removed.

[0032] Prescription composition: 50 parts ginseng, 12 parts Lysimachia christinae, 30 parts Poria cocos, 15 parts Ophiopogon japonicus, and 10 parts dragon bone.

[0033] Preparation: Take all the herbs, add water and decoct three times, each time for 2 hours, combine the decoctions and let stand for 24 hours. Filter, concentrate the filtrate to a relative density of 1.19-1.25, dry, pulverize, and package.

[0034] Comparative Example 3

[0035] The preparation of the traditional Chinese medicine composition differs from Example 1 in that the Lysimachia christinae is removed.

[0036] Prescription composition: 50 parts ginseng, 30 parts poria cocos, 15 parts ophiopogon japonicus, 10 parts dragon bone, and 2 parts cinnabar.

[0037] Preparation: Cinnabar is water-milled, then the remaining herbs are decocted three times with water, each time for 2 hours. The decoctions are combined and left to stand for 24 hours. The filtrate is filtered, concentrated to a relative density of 1.19-1.25, dried, pulverized, and mixed with the water-milled cinnabar. The mixture is then packaged.

[0038] In animal experiments, the drug powder was suspended in physiological saline before administration.

[0039] Refer to existing techniques (“Experimental study on isoproterenol-induced chronic heart failure of rats with myocardial ischemia”, Ren Haihua et al., Journal of Dali University, Vol. 10, No. 2, pp. 18-21, February 2011) to prepare a rat model of chronic heart failure and conduct animal experiments.

[0040] Healthy male Sprague-Dawley rats were selected for modeling. During the modeling period, isoproterenol (ISO) was administered intraperitoneally at a dose of 3.0 mg / kg·d for 3 consecutive days. After 4 weeks of observation, all rats exhibited varying degrees of shortness of breath, poor activity response, decreased urine output, mild edema, and decreased appetite. At the end of the 4th week, two rats were randomly selected for cardiac function testing and lung tissue pathological observation. The model group showed a slight decrease in blood pressure and left ventricular systolic pressure, but no pathological changes such as pulmonary congestion. In the 5th week, the rats were administered 2.0 mg / kg·d for 2 days. At the end of the 5th week, two rats from the model group and one rat from the control group were randomly selected again for cardiac function testing and lung tissue pathological observation. The model group showed a significant decrease in blood pressure (BP), left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), and maximum left ventricular systolic rate (+dp / dtmax), and mild pulmonary congestion pathological changes. In the 6th week, the rats were administered 3.0 mg / kg·d for another 2 days. By the end of week 6, all rats exhibited characteristic signs of heart failure, including decreased food and water intake, reduced exercise tolerance, shortness of breath, edema, and decreased body temperature. Therefore, modeling was completed. Color Doppler echocardiography was used to measure the left ventricular end-systolic volume, left ventricular end-diastolic volume, and left ventricular stroke volume in the modeled rats, and the left ventricular ejection fraction (LVEF) was calculated. Rats with LVEF ≤ 50% were considered eligible and selected for the drug administration experiment.

[0041] The therapeutic effects of the traditional Chinese medicine composition prepared in Example 1 of this invention and the traditional Chinese medicine compositions prepared in Comparative Examples 1-3 on model rats were investigated. The rats with successfully modeled chronic heart failure were used as experimental subjects and divided into 6 groups of 10 rats each: blank model group 1 (physiological saline 10 ml·kg⁻¹). -1 ·d -1 ), positive control group 2 (metoprolol succinate 7.6 mg / kg) -1 ·d -1 Example 1, herbal composition group 3 (crude drug 1.5g·kg) -1 ·d -1 Comparative Example 1: Herbal Composition Group 4 (crude drug 1.5g / kg) -1 ·d -1 Comparative Example 2: Herbal Composition Group 5 (crude drug 1.5g·kg) -1 ·d -1 Comparative Example 3: Herbal Composition Group 6 (crude drug 1.5g·kg) -1 ·d -1 ) Administered via gavage for 8 weeks.

[0042] At the end of the 8-week treatment period, the survival rates of SD rats in each group were as follows: blank model group n=7, positive control group n=10, Example 1 treatment group n=10, Comparative Example 1 treatment group n=8, Comparative Example 2 group n=9, and Comparative Example 3 group n=8. Echocardiography and cardiac function tests were performed again to observe various indicators.

[0043]

[0044] Table 1 shows the results for the positive control group 2 (metoprolol succinate 7.6 mg / kg). -1 ·d -1 Example 1, herbal composition group 3 (crude drug 8.5g·kg) -1 ·d -1 In rats, left ventricular ejection fraction (LVEF) significantly improved both before and after treatment, and the efficacy of the two treatments was similar. Although in Comparative Example 1, the herbal composition group 4 (crude drug 8.5 g / kg) showed improvement... -1 ·d -1 Comparative Example 2: Herbal Composition Group 5 (crude drug 8.5 g / kg) -1 ·d -1 Comparative Example 3: Herbal Composition Group 6 (crude drug 8.5 g / kg) -1 ·d -1 The left ventricular ejection fraction (LVEF) of rats in the study was improved before and after treatment, but the improvement was much smaller than that of the positive control group 2 and the herbal composition group in Example 1 3.

[0045]

[0046] Table 2 shows the results of left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), and maximum left ventricular systolic rate (+dp / dt) in rats in the positive control group 2 and the herbal composition group 3 of Example 1. max ), maximum diastolic velocity of the left ventricle (-dp / dt) max Both groups showed significant improvement before and after treatment, and their efficacy was similar. Although the levels of LVSP, LVDP, and +dp / dt in rats in Comparative Example 1 (group 4), Comparative Example 2 (group 5), and Comparative Example 3 (group 6) were significantly improved... max -dp / dt max Both groups showed some improvement before and after treatment, but the improvement was much smaller than that of the positive control group 2 and the traditional Chinese medicine composition group 3 in Example 1.

[0047] In summary, the present invention uses the aforementioned traditional Chinese medicines in combination to achieve a synergistic effect among the efficacy of each medicine. By replacing similar functional traditional Chinese medicines (ginseng, salvia miltiorrhiza) or removing some traditional Chinese medicines (cinnabar, lysimachia christinae), the composition still has a certain therapeutic effect on heart failure, but the effect is significantly reduced.

[0048] Example 2

[0049] Preparation of Traditional Chinese Medicine Compositions

[0050] Prescription composition: 25 parts ginseng, 6 parts Lysimachia christinae, 10 parts Poria cocos, 6 parts Ophiopogon japonicus, 5 parts dragon bone, and 1 part cinnabar.

[0051] Preparation: Cinnabar is water-milled. Then, the remaining herbs are decocted three times with five times the amount of water, each time for two hours. The decoctions are combined and left to stand for 24 hours. The filtrate is filtered, concentrated to a relative density of 1.19-1.25, dried, pulverized, and mixed with the water-milled cinnabar. The mixture is then packaged.

[0052] Example 3

[0053] Preparation of Traditional Chinese Medicine Compositions

[0054] Prescription composition: 100 parts ginseng, 20 parts Lysimachia christinae, 50 parts Poria cocos, 50 parts Ophiopogon japonicus, 25 parts dragon bone, and 4 parts cinnabar.

[0055] Preparation: Cinnabar is water-milled. Then, the remaining herbs are decocted three times with five times the amount of water, each time for two hours. The decoctions are combined and left to stand for 24 hours. The filtrate is filtered, concentrated to a relative density of 1.19-1.25, dried, pulverized, and mixed with the water-milled cinnabar. The mixture is then packaged.

[0056] The traditional Chinese medicine compositions described in Examples 2-3 were used to conduct drug administration tests on animals with chronic heart failure, and the results were similar to those in Example 1.

[0057] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating chronic heart failure, characterized in that, The composition is made from the following raw materials: ginseng 20-110 parts, Lysimachia christinae 5-25 parts, Poria cocos 8-60 parts, Ophiopogon japonicus 5-60 parts, dragon bone 5-30 parts, and cinnabar 0.5-5 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The composition is made from the following raw materials: 50 parts ginseng, 12 parts Lysimachia christinae, 30 parts Poria cocos, 15 parts Ophiopogon japonicus, 10 parts dragon bone, and 2 parts cinnabar.

3. A method for preparing the traditional Chinese medicine composition as described in claim 1, characterized in that, include: Take all the herbs except cinnabar, add water and decoct 1-3 times, each time for 1-3 hours, combine the decoctions, let stand for 24-48 hours, filter, concentrate the filtrate to a relative density of 1.1-1.4, dry, pulverize, add cinnabar and mix well.

4. The method according to claim 3, characterized in that, The process involves water-milling cinnabar, then taking the remaining herbs, adding 5 times the amount of water, and decocting them 3 times, 2 hours each time. The decoctions are combined, left to stand for 24 hours, filtered, and the filtrate is concentrated to a relative density of 1.19-1.

25. The filtrate is then dried, pulverized, and mixed with the water-milled cinnabar.

5. Use of the traditional Chinese medicine composition as described in claim 1 in the preparation of a medicament for treating chronic heart failure.

6. The use according to claim 5, characterized in that, The drug also includes pharmaceutically acceptable excipients.

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