A traditional Chinese medicine composition for treating dilated cardiomyopathy and a preparation method thereof

Abstract

The application discloses a traditional Chinese medicine composition for treating dilated cardiomyopathy, relates to the field of traditional Chinese medicines, and provides a traditional Chinese medicine composition for improving ventricular remodeling of a dilated cardiomyopathy patient, which is prepared from the following traditional Chinese medicines in parts by weight: radix astragali 60-90 parts, semen platycladi 15-30 parts, cortex mori 15-30 parts, ramulus cinnamomi 10-15 parts, zingiberis rhizoma siccum 10-15 parts, curcuma zedoaria 10-20 parts, cinnamomum cassia 6-10 parts and euonymus alatus 10-15 parts. The application has remarkable advantages in improving heart failure symptoms of the DCM patient, reversing ventricular remodeling, improving exercise tolerance, controlling arrhythmia and improving long-term prognosis of the patient.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition for treating dilated cardiomyopathy and its preparation method. Background Technology

[0002] Dilated cardiomyopathy (DCM) is a non-ischemic cardiomyopathy characterized by damage to the structure and function of the myocardium. It occurs after ruling out ischemic heart disease, hypertension, valvular heart disease, and congenital heart disease. The manifestations include ventricular enlargement and decreased myocardial contractility. DCM is the third leading cause of heart failure and the leading cause of heart transplantation. DCM can occur at any age, but it is most common in young and middle-aged adults. A 2002 survey in China estimated the prevalence of DCM to be approximately 19 per 100,000. Because a large number of asymptomatic individuals remain undetected, the true prevalence of DCM is likely significantly underestimated.

[0003] Disturbances and heart disease (DCM) are characterized by myocardial fibrosis. The key goals of DCM treatment are to prevent myocardial damage mediated by the primary cause, control heart failure and arrhythmias, prevent sudden death and embolism, and improve patients' quality of life and survival rate. Currently, Western medicine focuses on improving heart failure symptoms, inhibiting ventricular remodeling, and preventing arrhythmias and sudden death. Although the rapid development of drug and device treatments for heart failure has improved the quality of life and survival rate of most DCM patients, problems such as drug intolerance and inability to escalate to target doses still exist, making the clinical diagnosis and treatment of DCM face many challenges. Furthermore, studies show that the 5-year mortality rate of DCM remains as high as 15.5%, placing a heavy burden on society and families. Summary of the Invention

[0004] To address the aforementioned problems, this invention aims to provide a traditional Chinese medicine composition for treating dilated cardiomyopathy and its preparation method. This traditional Chinese medicine composition has a profound theoretical basis, a rigorous formulation, significant efficacy, is easy to prepare, has good patient compliance, and has no toxic side effects.

[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0006] A traditional Chinese medicine composition for treating dilated cardiomyopathy, characterized in that the composition is prepared from the following traditional Chinese medicines in parts by weight: 60-90 parts of raw Astragalus membranaceus, 15-30 parts of Lepidium apetalum, 15-30 parts of Morus alba root bark, 10-15 parts of Cinnamomum cassia twig, 10-15 parts of dried ginger, 10-20 parts of Curcuma zedoaria, 6-10 parts of Cinnamomum cassia bark, and 10-15 parts of Epimedium.

[0007] Furthermore, the traditional Chinese medicine composition is prepared from the following traditional Chinese medicines in parts by weight: 60 parts of raw Astragalus membranaceus, 15 parts of Lepidium apetalum, 15 parts of Morus alba root bark, 12 parts of Cinnamomum cassia twig, 10 parts of dried ginger, 15 parts of Curcuma zedoaria, 10 parts of Cinnamomum cassia bark, and 12 parts of Epimedium.

[0008] A method for preparing a traditional Chinese medicine composition for treating dilated cardiomyopathy, characterized by comprising the following steps:

[0009] Step 1: Weigh out the following ingredients in the order of weight: 60-90 parts of raw Astragalus membranaceus, 15-30 parts of Lepidium apetalum, 15-30 parts of Morus alba root bark, 10-15 parts of Cinnamomum cassia twig, 10-15 parts of dried ginger, 10-20 parts of Curcuma zedoaria, 6-10 parts of Cinnamomum cassia bark, and 10-15 parts of Epimedium brevicornu. Set aside.

[0010] Step 2: Crush each of the raw materials weighed in Step 1 into powder, mix them evenly to obtain a mixed powder, add water at room temperature and decoct for 40-50 minutes, then filter and separate to obtain a primary residue and a primary filtrate.

[0011] Step 3: Add three times the weight of water to the primary dregs from Step 2, decoct for 20-30 minutes, then filter and separate to obtain secondary dregs and secondary filtrate;

[0012] Step 4: Mix the primary filtrate from Step 2 and the secondary filtrate from Step 3 to obtain a mixed filtrate;

[0013] Step 5: Concentrate the mixed filtrate from Step 4 at 40℃-70℃ to obtain the traditional Chinese medicine composition.

[0014] Furthermore, in step 2, the weight ratio of the mixed powder to water is 1:5.

[0015] This application also discloses a medicament for treating dilated cardiomyopathy, characterized in that it comprises the traditional Chinese medicine composition as described in any one of claims 1 or 2.

[0016] Furthermore, the drug is prepared by adding excipients to a traditional Chinese medicine composition.

[0017] Furthermore, the dosage form of the drug is granules.

[0018] The formulation principle of the traditional Chinese medicine composition in this invention is based on the pathogenesis theory of DCM (Disordered Cognitive Metastasis) of "deficiency of Yang in the heart and lungs, sinking of Qi (vital energy), and obstruction of the heart meridians." DCM pathogenesis is complex and symptoms are varied, with "deficiency, stasis, and water retention" intertwined. However, its root cause lies in deficiency of Yang in the heart and lungs, sinking of Qi, and obstruction of the heart meridians. The heart, being a fire organ, distributes heat throughout the body, illuminating all things. The heart governs the blood, and the lungs govern the Qi. The heart governs the blood vessels, and the lungs govern the hundred vessels; the heart and lungs together govern the Yang Qi of the upper Jiao (upper burner). Zhang Xichun stated, "Both the heart and lungs are enveloped by the Qi in the chest, and their protective and dispersing power truly depends on the Qi." When the Qi in the chest is deficient, the heart's blood circulation is weak, leading to stagnation; when the Qi is deficient, the Qi transformation of the three Jiaos (upper, middle, and lower burners) is disrupted, and abnormal fluid metabolism results in edema and oliguria; when fluids invade the heart and lungs, and the lungs' dispersing and descending functions are disordered, chest tightness, shortness of breath, and inability to lie flat occur. When vital energy (Zong Qi) leaks out and the heart becomes arrhythmic, palpitations and anxiety occur. When vital energy is deficient and sinking, the Yang Qi of the upper Jiao (heart and lungs) is unable to effectively distribute heat to the spleen, and the middle Jiao (middle burner) is unable to properly digest and transform food, leading to poor appetite, abdominal distension, indigestion, and loose stools. When vital energy in the chest cannot nourish the lower Jiao (lower burner) and the body lacks warmth, cold limbs and aversion to cold occur. The main pathological change in the myocardium of DCM patients is myocardial fibrosis, with excessive deposition of collagen fibers in the myocardial tissue, an imbalance in the proportion and arrangement of different types of collagen, and the replacement of normal myocardial tissue by collagen fibers. Myocardial fibrosis and ventricular remodeling subsequently cause abnormalities in myocardial function, metabolism, and conduction, leading to heart failure and arrhythmias. Fibrotic myocardium should be classified under the category of "Zhengjia" in Traditional Chinese Medicine (TCM), and blood stasis in the heart meridians should be one of the characteristics of the TCM pathogenesis of DCM. In summary, the clinical symptoms and microscopic pathological changes of DCM patients are completely consistent with the pathogenesis of "deficiency of Yang Qi in the heart and lungs, sinking of vital energy, and blood stasis in the heart meridians."

[0019] The beneficial effects of this invention are: compared with the prior art, the improvement of this invention lies in that...

[0020] Based on in-depth research into classical Chinese medicine theories and combined with years of clinical experience, the inventor created a Chinese herbal composition to treat this type of disease. In this formula, Astragalus membranaceus is sweet and warm, entering the spleen and lung meridians, which can greatly replenish the qi of the spleen and lungs to promote blood circulation and fluid transport, and also lift yang and raise prolapse; Lepidium apetalum and Morus alba bark are used together to lift the lung qi, open up the lung qi, and promote the upper source of water metabolism; Cinnamomum cassia and Zingiber officinale are pungent and sweet, which can warm and invigorate the yang of the heart and spleen, transform qi to promote water metabolism, and also warm the meridians and unblock the vessels; Curcuma zedoaria is bitter, pungent, and warm, which can break up blood stasis, dissipate nodules, and improve the obstruction of the heart meridian; Cinnamomum cassia and Epimedium are pungent, sweet, and very hot, entering the Kidney meridian of Foot Shaoyin, which can greatly replenish the fire of the gate of life to help the kidney qi transform and promote water metabolism. This formula focuses on the three key pathological aspects of DCM—deficiency, stasis, and water retention—and the four major organs closely related to the metabolism of Qi, blood, and body fluids: the lungs, heart, spleen, and kidneys. It emphasizes tonifying Qi and warming Yang, lifting Yang and resolving prolapse, opening and dispersing lung Qi, promoting water metabolism, breaking up blood stasis, clearing the channels, and eliminating masses. This embodies the innovative application of the theory of "tonifying Qi to promote lifting, using gentle heat to generate Qi, and promoting water metabolism to unblock Yang" in DCM. Clinically, this formula is mainly used in the form of a decoction of the prepared Chinese herbal composition and in granules prepared by concentrating the decoction into a clear paste and adding dextrin as an excipient. Both forms can be taken clinically. Since its clinical use, it has been highly praised by patients for its significant efficacy. Attached Figure Description

[0021] Figure 1 This is the pre-treatment echocardiogram report for Case 1 of this invention.

[0022] Figure 2 This is a cardiac ultrasound report after treatment for Case 1 of the present invention.

[0023] Figure 3 This is the pre-treatment echocardiogram report for Case 2 of this invention.

[0024] Figure 4 This is a cardiac ultrasound report after treatment in Case 2 of this invention. Detailed Implementation

[0025] To enable those skilled in the art to better understand the technical solutions of the present invention, the technical solutions of the present invention will be further described below in conjunction with the accompanying drawings and embodiments.

[0026] Example 1

[0027] This invention provides a traditional Chinese medicine composition for treating dilated cardiomyopathy, which is prepared from the following traditional Chinese medicines in parts by weight: 60 parts of raw Astragalus membranaceus, 15 parts of Lepidium apetalum, 15 parts of Morus alba root bark, 12 parts of Cinnamomum cassia twig, 10 parts of dried ginger, 15 parts of Curcuma zedoaria, 10 parts of Cinnamomum cassia bark, and 12 parts of Epimedium.

[0028] Example 2

[0029] This invention provides a traditional Chinese medicine composition for treating dilated cardiomyopathy, which is prepared from the following traditional Chinese medicines in parts by weight: 75 parts of raw Astragalus membranaceus, 20 parts of Lepidium apetalum, 20 parts of Morus alba root bark, 12 parts of Cinnamomum cassia twig, 10 parts of dried ginger, 15 parts of Curcuma zedoaria, 6 parts of Cinnamomum cassia bark, and 13 parts of Epimedium.

[0030] Example 3

[0031] This invention provides a traditional Chinese medicine composition for treating dilated cardiomyopathy, which is prepared from the following traditional Chinese medicines in parts by weight: 90 parts of raw Astragalus membranaceus, 30 parts of Lepidium apetalum, 30 parts of Morus alba root bark, 15 parts of Cinnamomum cassia twig, 15 parts of dried ginger, 20 parts of Curcuma zedoaria, 10 parts of Cinnamomum cassia bark, and 15 parts of Epimedium.

[0032] This invention provides a method for preparing the traditional Chinese medicine composition for treating dilated cardiomyopathy obtained in Example 1, comprising the following steps:

[0033] Step 1: Weigh out 60 parts of raw Astragalus membranaceus, 15 parts of Lepidium apetalum, 15 parts of Morus alba root bark, 12 parts of Cinnamomum cassia twig, 10 parts of dried ginger, 15 parts of Curcuma zedoaria, 10 parts of Cinnamomum cassia bark, and 12 parts of Epimedium according to their weight and set aside.

[0034] Step 2: Crush each raw material in Step 1 into coarse powder and mix them evenly. Add water equal to 5 times the weight of each raw material in Step 1 at room temperature and decoct for 40 minutes. Then filter and separate to obtain a first batch of residue and a first batch of filtrate.

[0035] Step 3: Add three times the weight of water to the primary dregs from Step 2, decoct for 25 minutes, then filter and separate to obtain secondary dregs and secondary filtrate;

[0036] Step 4: Mix the primary filtrate from Step 2 and the secondary filtrate from Step 3 to obtain a mixed filtrate;

[0037] Step 5: Concentrate the mixed filtrate from Step 4 at 50°C to obtain the traditional Chinese medicine composition.

[0038] Preferably, in step 2, the weight ratio of the mixed powder to water is 1:5.

[0039] The traditional Chinese medicine composition of this application can also be concentrated into a clear paste based on the decoction, and granules can be prepared by adding the excipient dextrin. Both the decoction and the granules can be taken clinically.

[0040] It should be noted that "qinggao" is a medical term. The "qing" in qinggao refers to the fact that the paste has been concentrated to a viscous state during the preparation process, so there is no need to add sugars (such as honey, rock sugar, white sugar, brown sugar, maltose, etc.) or animal glue for thickening.

[0041] Based on the traditional Chinese medicine composition for treating dilated cardiomyopathy in Example 1, if the patient has severe dampness, 10g of Polyporus umbellatus, 20g of Poria cocos, 10g of Alisma plantago-aquatica, and 30g of Plantago asiatica can be added clinically.

[0042] Based on the traditional Chinese medicine composition for treating dilated cardiomyopathy in Example 1, if the patient experiences palpitations and restlessness, add 10g of prepared licorice root, 30g of dragon bone, and 30g of oyster shell.

[0043] Based on the traditional Chinese medicine composition for treating dilated cardiomyopathy in Example 1, if the patient has severe blood stasis, add 15g of Ligusticum chuanxiong, 10g of Curcuma longa, and 15g of Corydalis yanhusuo.

[0044] Based on the traditional Chinese medicine composition for treating dilated cardiomyopathy in Example 1, if the patient has severe qi deficiency, add 10g of ginseng, 15g of stir-fried Atractylodes macrocephala, and 20g of Codonopsis pilosula.

[0045] The specific method of using the traditional Chinese medicine composition provided in this embodiment of the invention is as follows: The traditional Chinese medicine composition is a decoction or granules. Here, the decoction is used as an example for explanation. When taking the decoction, the mixed filtrate of the traditional Chinese medicine composition of this application is concentrated and packaged, sterilized, and the decoction is obtained. One bag is taken each time, twice a day.

[0046] The following is a typical case 1 of applying the traditional Chinese medicine composition provided in Example 1.

[0047] Patient's basic information: Patient Qiao, male, 73 years old, experienced chest tightness, shortness of breath, and palpitations after walking 500 meters in May 2022. These symptoms were relieved after 10-20 minutes of rest. He had no chest pain, dizziness, or blurred vision. After completing relevant examinations at Peking University Third Hospital, he was diagnosed with "dilated cardiomyopathy." On May 19, 2022, a cardiac ultrasound at Peking University Third Hospital showed diffuse reduction in left ventricular wall motion, uncoordinated left ventricular motion, enlargement of the left atrium and left ventricle, mild aortic regurgitation, moderate mitral regurgitation, reduced left ventricular diastolic function, left ventricular ejection fraction (LVEF) of 34%, and left ventricular end-diastolic diameter (LVEDd) of 63.3 mm. The patient was prescribed the following oral Western medicines: enteric-coated aspirin 0.1g once daily, sacubitril / valsartan 100mg twice daily, atorvastatin calcium tablets 20mg once daily, ivabradine hydrochloride 2.5mg twice daily, dapagliflozin 5mg once daily, spironolactone 20mg once daily, bisoprolol fumarate 2.5mg once daily, and glimepiride 2mg once daily. In September 2022, the patient visited our hospital, and an echocardiogram showed: LVEF 34%, LVEDd 60mm (…). Figure 1 As shown), in addition to conventional Western medicine, the clinical prescription used the traditional Chinese medicine composition of this invention as the core drug. After about 6 months of treatment, the patient's symptoms such as chest tightness, shortness of breath, fatigue, and palpitations significantly improved. An echocardiogram showed: LVEF 45%, LVEDd 56mm. Figure 2(As shown). LVEF increased by 11% compared to before, and LVEDd decreased by 4mm.

[0048] The following is a typical case 2 using the traditional Chinese medicine composition provided in Example 1.

[0049] Patient's basic information: Patient Dong, male, 51 years old, experienced chest tightness, weakness, shortness of breath, and bilateral lower extremity edema after activity in April 2023. On June 13, 2023, he visited Beijing Anzhen Hospital. Echocardiography showed: generally reduced left and right ventricular wall motion, enlarged left and right atria, moderate mitral regurgitation, moderate tricuspid regurgitation, and overall decreased cardiac function, LVEF 26%, LVEDd 58mm. After completing relevant auxiliary examinations, he was diagnosed with "dilated cardiomyopathy and atrial fibrillation". He was prescribed oral Western medicine: rivaroxaban 15mg qd, fenelizumab 10mg qd, sacubitril / valsartan 25mg bid, dapagliflozin 10mg qd, velixithidine 5mg qd, metoprolol succinate extended-release tablets 71.25mg qd, and tolvaptan 7.5mg qd. The patient visited our hospital in October 2023. An echocardiogram showed: LVEF 28%, LVEDd 56mm. Figure 3 As shown), in addition to conventional Western medicine, the clinical prescription used the traditional Chinese medicine composition of this invention as the core drug. After about 6 months of treatment, the patient's symptoms such as chest tightness, wheezing, shortness of breath, and fatigue significantly improved. An echocardiogram showed: LVEF 45%, LVEDd 50mm. Figure 4 (As shown). LVEF increased by 17% compared to before, and LVEDd decreased by 6mm.

[0050] The following is a clinical observation of the application effects of traditional Chinese medicine compositions.

[0051] This study included 22 patients with dilated cardiomyopathy (DCM) who visited the Department of Cardiovascular Medicine at Xiyuan Hospital of the China Academy of Chinese Medical Sciences between March 2021 and December 2023. Among them, 17 were male and 5 were female. The average age was 55.73 years, and all were Han Chinese. The duration of DCM history ranged from 0.08 to 16 years. Eight patients had a history of hypertension, 8 had diabetes, 8 had dyslipidemia, 4 had coronary artery disease, 5 had moderate to severe mitral regurgitation, 2 had moderate to severe tricuspid regurgitation, 4 had atrial fibrillation, 11 had frequent premature ventricular contractions, 3 had paroxysmal ventricular tachycardia, 4 had a history of COPD, 1 had a history of cerebral infarction, and 4 had abnormal renal function. 22 patients were taking beta-blockers, 21 were taking ACEI / ARB / ARNI, 19 were taking MRA, and 5 were taking SGLT2 inhibitors. One patient had an ICD implanted, and one had a CRT-D implanted. Nine of them had a history of smoking, and 11 had a history of drinking.

[0052] Treatment methods:

[0053] In addition to taking conventional Western medicine according to the "Guidelines for the Diagnosis and Treatment of Dilated Cardiomyopathy in China" formulated by the Chinese Society of Cardiology, 22 patients with dilated cardiomyopathy underwent individualized treatment. They also took granules made from the traditional Chinese medicine composition described in this application, one sachet three times a day, for 24 weeks.

[0054] Therapeutic efficacy evaluation indicators:

[0055] Changes in heart rate, blood pressure, New York Heart Association (NYHA) classification, Kansas City Cardiomyopathy Scale (KCCQ), Traditional Chinese Medicine syndrome scoring scale, and left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD) measured by echocardiography before and after 24 weeks of treatment.

[0056] Therapeutic effect evaluation:

[0057] Intragroup comparisons showed that in patients with dilated cardiomyopathy, heart rate, TCM syndrome score, and left ventricular end-diastolic diameter were significantly lower after treatment (P < 0.05). Systolic blood pressure, Kansas City Cardiomyopathy Scale score, and left ventricular ejection fraction were significantly higher after treatment (P < 0.05). However, there was no significant change in diastolic blood pressure before and after treatment (P > 0.05).

[0058]

[0059] Security Analysis:

[0060] This study used white blood cell count (WBC), red blood cell count (RBC), platelet count (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (CREA), prothrombin time (PT), and activated partial thromboplastin time (APTT) as indicators for evaluating laboratory safety. Abnormal laboratory test results were defined as normal or abnormal but clinically insignificant laboratory tests before treatment, followed by clinically significant abnormalities after treatment, or abnormal laboratory tests before treatment but worsening after treatment. Results showed that no patients experienced abnormalities in laboratory safety indicators.

[0061]

[0062] Treatment conclusion:

[0063] The traditional Chinese medicine composition of this application can improve ventricular remodeling and quality of life in patients with dilated cardiomyopathy, and has high safety in clinical application.

[0064] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of this invention is defined by the appended claims and their equivalents.

Claims

1. A traditional Chinese medicine composition for treating dilated cardiomyopathy, characterized in that: The traditional Chinese medicine composition is prepared from the following traditional Chinese medicines in parts by weight: 60-90 parts of raw Astragalus membranaceus, 15-30 parts of Lepidium apetalum, 15-30 parts of Morus alba root bark, 10-15 parts of Cinnamomum cassia twig, 10-15 parts of dried ginger, 10-20 parts of Curcuma zedoaria, 6-10 parts of Cinnamomum cassia bark, and 10-15 parts of Epimedium.

2. The traditional Chinese medicine composition for treating dilated cardiomyopathy according to claim 1, characterized in that: The traditional Chinese medicine composition is prepared from the following traditional Chinese medicines in parts by weight: 60 parts of raw Astragalus membranaceus, 15 parts of Lepidium apetalum, 15 parts of Morus alba root bark, 12 parts of Cinnamomum cassia twig, 10 parts of dried ginger, 15 parts of Curcuma zedoaria, 10 parts of Cinnamomum cassia bark, and 12 parts of Epimedium.

3. A method for preparing a traditional Chinese medicine composition for treating dilated cardiomyopathy, characterized in that, Includes the following steps: Step 1: Weigh out the following ingredients in the order of weight parts according to the traditional Chinese medicine composition described in claim 1 or 2: Astragalus membranaceus, Lepidium apetalum, Morus alba root bark, Cinnamomum cassia twig, Zingiber officinale, Curcuma zedoaria, Cinnamomum cassia bark, and Epimedium brevicornu. Step 2: Crush each of the raw materials weighed in Step 1 into powder, mix them evenly to obtain a mixed powder, add water at room temperature and decoct for 40-50 minutes, then filter and separate to obtain a primary residue and a primary filtrate. Step 3: Add three times the weight of water to the primary dregs from Step 2, decoct for 20-30 minutes, then filter and separate to obtain secondary dregs and secondary filtrate; Step 4: Mix the primary filtrate from Step 2 and the secondary filtrate from Step 3 to obtain a mixed filtrate; Step 5: Concentrate the mixed filtrate from Step 4 at 40℃-70℃ to obtain the traditional Chinese medicine composition.

4. The method for preparing a traditional Chinese medicine composition for treating dilated cardiomyopathy according to claim 3, characterized in that, In step 2, the weight ratio of the mixed powder to water is 1:

5.

5. A drug for treating dilated cardiomyopathy, characterized in that, Made from the traditional Chinese medicine composition according to any one of claims 1 or 2.

6. The medicament for treating dilated cardiomyopathy according to claim 5, characterized in that, The drug is prepared by adding excipients to a traditional Chinese medicine composition.

7. The medicament for treating dilated cardiomyopathy according to claim 5, characterized in that, The drug is in granule form.

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