Traditional chinese medicine composition for treating coronary myocardial bridge and application thereof

Abstract

A traditional Chinese medicine composition for treating coronary myocardial bridge and an application thereof are provided. The traditional Chinese medicine composition includes the following components in parts by weight: 2-10 parts of scorpion, 2-10 parts of centipede, 15-50 parts of Radix paeoniae Alba, 5-25 parts of Radix glycyrrhizae Preparata, 10-30 parts of Rhizoma chuanxiong, 10-30 parts of Radix curcumae and 10-30 parts of Rhizoma corydalis.

Claims

1. A medicine composition for treating coronary myocardial bridge, wherein the medicine composition comprising the following components in parts by weight: 2-10 parts of scorpion, 2-10 parts of centipede, 15-50 parts of Radix paeoniae Alba, 5-25 parts of Radix glycyrrhizae Preparata, 10-30 parts of Rhizoma chuanxiong, 10-30 parts of Radix curcumae and 10-30 parts of Rhizoma corydalis.

2. The medicine composition according to claim 1, wherein the medicine composition comprising the following components in parts by weight: 3 parts of scorpion, 2 parts of centipede, 30 parts of Radix paeoniae Alba, 10 parts of Radix glycyrrhizae Preparata, 15 parts of Rhizoma chuanxiong, 15 parts of Radix curcumae and 15 parts of Rhizoma corydalis.

3. The medicine for treating coronary myocardial bridge, wherein raw materials comprise the medicine composition according to claim 1.

4. The medicine according to claim 3, wherein the medicine also comprises pharmaceutically acceptable excipients.

5. The medicine according to claim 4, wherein the excipients comprise an emulsifier, a filler, a binder, a disintegrant, a colorant and/or a cosolvent.

6. The medicine according to claim 5, wherein a dosage form of the medicine is an oral dosage form.

7. The medicine according to claim 6, wherein the oral dosage form is decoction, granule, capsule, pill, tablet or ointment.

8. A medicine for treating coronary myocardial bridge, wherein raw materials comprise the medicine composition according to claim 2.

9. A preparation method of the medicine according to claim 4, comprising steps of extracting active ingredients in the medicine composition by using a solvent, and then adding the pharmaceutically acceptable excipients to prepare the medicine.

10. A method for treating coronary myocardial bridge in a subject in need thereof comprising administering the medicinal composition according to claim 1 to said subject.

11. A method for treating coronary myocardial bridge in a subject in need thereof comprising administering the medicinal composition according to claim 2 to said subject.

Description

DETAILED DESCRIPTION OF THE EMBODIMENTS

(1) A number of exemplary embodiments of the present disclosure will now be described in detail, and this detailed description should not be considered as a limitation of the present disclosure, but should be understood as a more detailed description of certain aspects, characteristics and embodiments of the present disclosure.

(2) It should be understood that the terminology described in the present disclosure is only for describing specific embodiments and is not used for limiting the present disclosure. In addition, for the numerical range in the present disclosure, it should be understood that each intermediate value between the upper limit and the lower limit of the range is also specifically disclosed. Intermediate values within any stated value or stated range, as well as each smaller range between any other stated value or intermediate values within the stated range are also included in the present disclosure. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

(3) Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention relates. Although the present disclosure only describes the preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present disclosure. All documents mentioned in this specification are incorporated by reference to disclose and describe methods and/or materials related to the documents. In case of conflict with any incorporated document, the contents of this specification shall prevail.

(4) It is obvious to those skilled in the art that many improvements and changes may be made to the specific embodiments of the present disclosure without departing from the scope or spirit of the present disclosure. Other embodiments will be apparent to the skilled person from the description of the present disclosure. The description and embodiments of the present disclosure are exemplary only.

(5) The terms including, comprising, having and containing used herein are all open terms, which means including but not limited to.

(6) In the preparation method of the dosage form of the traditional Chinese medicine composition in the following embodiments, the decoction is prepared by washing the weighed raw materials and adding water for cooking; the granule is prepared by weighing raw materials respectively, cleaning and cooking, filtering and combining filtrates, concentrating the filtrates, cooling, adding ethanol, mixing uniformly, standing, weighing supernatant, filtering, distilling the filtrate to remove ethanol, standing and concentrating to obtain extract, and drying and pulverizing the extract to obtain granules; the capsule is prepared by adding excipients after the extract is prepared according to the method of preparing the granule, drying, pulverizing and granulating, and filling into the capsule. Other existing dosage forms, such as pills, tablets, decoctions, etc., may be prepared according to conventional preparation methods, and will not be repeated here.

Embodiment 1

(7) This embodiment provides a decoction prepared from the following raw materials:

(8) 30 grams (g) of Radix paeoniae Alba, 6 g of Radix glycyrrhizae Preparata, 3 g of scorpion, 2 g of centipede, 15 g of Rhizoma chuanxiong, 15 g of Radix curcumae and 15 g of Rhizoma corydalis.

Embodiment 2

(9) This embodiment provides a decoction prepared from the following raw materials:

(10) 15 g of Radix paeoniae Alba, 15 g of Radix glycyrrhizae Preparata, 3 g of scorpion, 2 g of centipede, 15 g of Rhizoma Chuanxiong, 15 g of Radix curcumae and 15 g of Rhizoma corydalis.

Embodiment 3

(11) This embodiment provides a decoction prepared from the following raw materials:

(12) 20 g of Radix paeoniae Alba, 10 g of Radix glycyrrhizae Preparata, 5 g of scorpion, 5 g of centipede, 15 g of Rhizoma chuanxiong, 15 g of Radix curcumae and 15 g of Rhizoma corydalis.

Embodiment 4

(13) This embodiment provides a granule prepared from the following raw materials:

(14) 50 g of Radix paeoniae Alba, 5 g of Radix glycyrrhizae Preparata, 2 g of scorpion, 10 g of centipede, 10 g of Rhizoma chuanxiong, 10 g of Radix curcumae and 10 g of Rhizoma corydalis.

Embodiment 5

(15) This embodiment provides a capsule prepared from the following raw materials:

(16) 30 g of Radix paeoniae Alba, 25 g of Radix glycyrrhizae Preparata, 10 g of scorpion, 5 g of centipede, 30 g of Rhizoma chuanxiong, 30 g of Radix curcumae and 30 g of Rhizoma corydalis.

(17) Effect Verification:

(18) According to the observation of clinical cases, the clinical efficacy of the traditional Chinese medicine composition according to the present disclosure in treating coronary myocardial bridge is verified by taking the frequency and duration of angina pectoris attack, ST-T segment change of electrocardiogram, left ventricular ejection fraction (LVEF) and quality of life index integral as observation indexes.

1. Materials and Methods

(19) 1.1 General Information

(20) The subjects were 180 cases of myocardial bridge diagnosed and treated in the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from March 2016 to March 2023, which met the inclusion and exclusion criteria.

(21) 1.2 Diagnostic Criteria

(22) Diagnostic criteria of western medicine: with reference to Diagnosis and Treatment of Coronary Myocardial Bridge edited by ZHANG Zhishou in 2020: during the hospital, the patient was found to have a coronary artery with different degrees of stenosis at more than two projection angles, and the blood supply of the coronary artery returned to normal at the end of diastole, that is, the milking effect, which may be diagnosed as coronary myocardial bridge, and the Noble grade of coronary myocardial bridge is grade II-III.

(23) Noble grade of coronary myocardial bridge: grade I, the severity of systolic compression of mural coronary artery is less than 50%, and there is no clinical manifestation; grade II, the severity of systolic compression of mural coronary artery is 50%-75%, with increased lactate and regional myocardial ischemia; grade III, the severity of systolic compression of mural coronary artery is more than 75%, with a significant increase in lactate and myocardial ischemia on electrocardiogram, and the appearance of clinical symptoms.

(24) Diagnostic criteria of traditional Chinese medicine: with reference to the diagnostic criteria of chest obstruction and heartache in Internal Medicine of Traditional Chinese Medicine published by China Traditional Chinese Medicine Publishing House in 2021.

(25) 1.3 Inclusion Criteria

(26) {circle around (1)} Meeting the diagnostic criteria of coronary myocardial bridge in western medicine and the myocardial bridge grade is grade II-III. {circle around (2)} Meeting the diagnostic criteria of chest obstruction and heartache in traditional Chinese medicine.
1.4 Exclusion Criteria {circle around (1)} Not meeting the diagnostic criteria of western medicine and traditional Chinese medicine at the same time. {circle around (2)}) There are serious life-threatening diseases such as heart, liver, kidney, hematopoietic system diseases or malignant tumors. {circle around (3)} Patients with multiple coronary artery lesions or single coronary artery stenosis exceeding 70%. {circle around (4)} Patients with heart rate <60 beats per minute (beats/min), blood pressure <100/70 millimeter of mercury (mmHg) or with atrioventricular block and sick sinus syndrome; {circle around (5)} People who are allergic to known ingredients of the medication.
1.5 Suspension Criteria {circle around (1)} Abnormal safety indexes such as liver function, kidney function and coagulation function occurred during the treatment. {circle around (2)} Acute diseases such as acute myocardial infarction, severe arrhythmia and cardiogenic shock occurred during the treatment. {circle around (3)} Special physiological conditions or unexpected events occurred during the research.
1.6 Research Methods
1.6.1 Treatment Method

(27) 180 cases meeting the inclusion and exclusion criteria were randomly divided into three groups of group A, group B and group C, with 60 cases in each group. The general data of the three groups were comparable (P>0.05).

(28) Group A: The decoction of Chinese medicinal composition prepared in Embodiment 1 was taken orally, with the dosage of 100 millilitre each time (mL/time), once in the morning, once in the afternoon and once in the evening every day, 30 minutes after meals, and 8 weeks was a course of treatment.

(29) Group B: The decoction of Chinese medicinal composition prepared in Embodiment 2 was taken orally, with the dosage of 100 mL/time, once in the morning, once in the afternoon and once in the evening every day, 30 minutes after meals, and 8 weeks was a course of treatment.

(30) Group C: Diltiazem hydrochloride sustained-release capsules 90 mg were taken orally once a day for 8 weeks as a course of treatment.

(31) During the treatment, blood pressure and heart rate were monitored, and oral nitrates (nitroglycerin tablets, isosorbide dinitrate tablets, etc.) were prohibited, and irritating drinks such as spirits, coffee and strong tea were avoided, spicy, greasy and cold foods were avoided, and strenuous exercise was avoided. Patients with other basic diseases continued to take conventional western medicine orally.

(32) Observation Indexes

(33) {circle around (1)} The frequency and duration of angina pectoris attacks and the improvement of ST-T segment on electrocardiogram: {circle around (2)} left ventricular ejection fraction (LVEF); {circle around (3)} quality of life index integral (SF-12).

(34) The evaluation criteria for the efficacy of the frequency and duration of angina pectoris attacks and ST-T segment changes on electrocardiogram: marked effect: angina pectoris symptoms basically improved, and ST-T segment on electrocardiogram returned to normal or almost normal; effective: the frequency and duration of angina pectoris attacks were obviously reduced, the ST-T segment on electrocardiogram rebounded by 0.05 millivolt (mV) or the inverted T wave became shallower by 25%, or the T wave changed from flat to upright, and the conduction block was improved; ineffective: the symptoms of angina pectoris have not improved significantly, and the ST-T segment on electrocardiogram has not changed.

(35) 1.6.3 Safety Evaluation

(36) After 8 weeks of treatment, the functions of liver, kidney and blood coagulation, routine blood, urine and stool were detected.

(37) 1.6.4 Statistical Method

(38) SPSS26.0 statistical software was used to analyze the data. The measurement data were expressed by meanstandard deviation (xs), and the paired t test was used for comparison before and after treatment in the group, and the independent sample t test was used for comparison before and after treatment in the group; rank sum test was used to compare grade data; chi-square test was used for counting data, with P<0.05 as statistical difference and P<0.01 as significant difference.

2. Results

(39) 2.1 Improvement of Frequency and Duration of Angina Pectoris Attacks

(40) After treatment, the frequency and duration of angina pectoris attacks in three groups were improved (P<0.05), especially in group A (P<0.01), and the specific results are shown in Table 1.

(41) TABLE-US-00001 TABLE 1 Comparison of frequency and duration of angina pectoris attacks before and after treatment (x s) Number of angina attacks Duration of angina pectoris (times/day) (min/day) Before After Before After Group Case treatment treatment treatment treatment Group A 59 26.34 4.35 4.28 2.30.sup.# 86.72 10.59 16.43 3.92.sup.# Group B 59 25.72 2.53 8.13 3.34.sup.# 88.50 8.61 23.95 4.19* Group C 58 25.96 1.19 11.64 4.68* 87.04 8.27 39.37 4.37* Note: Compared with before treatment, *P < 0.05, and compared with before treatment .sup.#P < 0.01.
2.2 Evaluation of Curative Effect of Angina Pectoris

(42) After treatment, 11 cases (18.64%) in group A were markedly effective, 37 cases (62.71%) were effective and 11 cases (18.64%) were ineffective. In group B, 7 cases were markedly effective (11.86%), 37 cases were effective (62.71%) and 15 cases were ineffective (25.42%). In group C, 3 cases were markedly effective (5.17%), 21 cases were effective (36.21%) and 36 cases were ineffective (62.07%). The total effective rate of the traditional Chinese medicine composition group in Embodiment 1 was 81.36%, and there was a statistical difference between the groups (P<0.05), as shown in Table 2.

(43) TABLE-US-00002 TABLE 2 Frequency and duration of angina pectoris attacks and evaluation of curative effect of ST-T segment changes on electrocardiogram Total Markedly effective Group Case effective Effective Ineffective rate Group A 59 11 (18.64%) 37 (62.71%) 11 (18.64%) 81.36% Group B 59 7 (11.86%) 37 (62.71%) 15 (25.42%) 74.58% Group C 58 3 (5.17%) 21 (36.21%) 36 (62.07%) 41.38%
2.3 Improvement of Left Ventricular Ejection Fraction

(44) After treatment, the ejection fraction of patients in group A increased from 53.684.06% to 57.223.17%; in group B, the ejection fraction of patients increased from 52.572.85% to 55.112.33%; in group C, the ejection fraction of patients increased from 52.443.91% to 53.602.77%, and the ejection fraction of Chinese medicine composition in Embodiment 1 was the most significant, with a statistical difference within the group (P<0.05), as shown in Table 3.

(45) TABLE-US-00003 TABLE 3 Improvement of left ventricular ejection fraction (%) Before After Group Case treatment treatment Group A 59 53.68 4.06 57.22 3.17* Group B 59 52.57 2.85 55.11 2.33* Group C 58 52.44 3.91 53.60 2.77* Note: Compared with before treatment *P < 0.05.
2.4 Quality of Life Index Integral Improvement

(46) After treatment, the quality of life index integral of patients in group A increased from 43.123.20 to 53.062.22; in group B, the quality of life index integral increased from 44.022.76 to 48.591.51; the quality of life index integral of patients in group C increased from 43.372.47 to 46.232.35, and the quality of life integral of Chinese medicine composition in Embodiment 1 was the most significant, with a statistical difference within the group (P<0.05), as shown in Table 4.

(47) TABLE-US-00004 TABLE 4 Quality of life index integral improvement Before After Group Case treatment treatment Group A 59 43.12 3.20 53.06 2.22* Group B 59 44.02 2.76 48.59 1.51* Group C 58 43.37 2.47 46.23 2.35* Note: Compared with before treatment *P < 0.05.
2.5 Safety Evaluation

(48) No adverse reactions were observed in patients in each group during 8 weeks, blood, urine, and stool routine, as well as liver and kidney function, showed no abnormalities.