Traditional Chinese medicine composition for preventing and treating sepsis myocardial injury as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for preventing and treating sepsis myocardial injury and a preparation method and application thereof. The composition consists of the following medicinal materials in parts by weight: 6-10 parts of peach kernel, 6-10 parts of safflower, 3-6 parts of coptis chinensis, 3-6 parts of felwort, 10-15 parts of fructus forsythiae, 10-15 parts of salvia miltiorrhiza, 6-12 parts of angelica sinensis, 3-8 parts of radix aconiti lateralis preparata, 3-6 parts of rhizoma zingiberis, 10-15 parts of calcined dragon bone, 6-10 parts of fructus aurantii, 6-10 parts of platycodon grandiflorum, 10-15 parts of caulis spatholobi, 10-15 parts of radix rehmanniae and 3-6 parts of honey-fried licorice root. The invention provides a self-prepared traditional Chinese medicine composition for preventing and treating sepsis myocardial injury, and the traditional Chinese medicine composition accurately aims at complex pathogenesis (toxin, blood stasis and deficiency interweaving) of sepsis myocardial injury through multi-dimensional, dynamic and integral intervention, and realizes systematic regulation which is difficult to achieve by a single medicine in western medicine.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition for preventing and treating myocardial injury in sepsis, its preparation method, and its application. Background Technology

[0002] Sepsis is a severe systemic infectious disease characterized by a strong inflammatory response in the body to an infectious agent (bacteria, viruses, fungi, or other microorganisms), leading to systemic inflammatory response syndrome (SIRS). It is one of the most acute and critical clinical conditions, with typical symptoms including fever, tachycardia, tachypnea, hypotension, and tissue hypoxia. A global study indicated that the overall mortality rate of sepsis is approximately 20%, but in critically ill patients, it can exceed 40%. Excessive activation of the inflammatory response in sepsis can lead to multiple organ dysfunction syndrome (MODS), which can be life-threatening in severe cases. Myocardial injury is a common manifestation of MODS; statistics show that approximately 50% of sepsis patients have concurrent myocardial dysfunction, further increasing the mortality rate. Therefore, the treatment of myocardial injury in sepsis is a crucial step in reducing sepsis mortality, and in-depth research into the pathophysiology and treatment strategies of myocardial injury in sepsis has significant social value and importance.

[0003] One of the serious complications of sepsis is septic myocardial injury, which poses a severe threat to patients' survival and quality of life. As a serious infectious disease, the treatment of septic myocardial injury has always been a hot topic in the medical field. With the continuous development and progress of modern medical technology, a series of diagnostic and treatment methods and approaches have emerged, aiming to improve patients' survival rates and quality of life. Clinical treatment mainly includes drug therapy, supportive therapy, interventional therapy, and immunomodulation, among other aspects.

[0004] Currently, Western medicine treatment of septic myocardial injury faces three major bottlenecks: complex mechanisms, contradictory treatment approaches, and delayed effects. It requires solutions such as developing multi-target drugs (e.g., dual anti-inflammatory and antioxidant molecules), establishing early warning models (genes + biomarkers + imaging), and promoting phenotype-guided individualized treatment. Traditional Chinese medicine (TCM) treatment of septic myocardial injury has advantages in its holistic regulation, multi-target intervention, reduction of secondary damage, and individualized treatment, particularly in improving myocardial microcirculation, inhibiting inflammatory storms, and regulating energy metabolism. Therefore, exploring more TCM compound formulas with significant efficacy in treating septic myocardial injury is of great clinical significance. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a self-formulated traditional Chinese medicine composition for the prevention and treatment of sepsis-induced myocardial injury. This composition, through multi-dimensional, dynamic, and holistic intervention, precisely targets the complex pathogenesis (intertwined toxins, blood stasis, and deficiency) of sepsis-induced myocardial injury, achieving systemic regulation that is difficult to achieve with single-drug Western medicine. Specifically, this invention conducts an in-depth analysis of the causes of sepsis-induced myocardial injury and formulates corresponding treatment principles, ultimately forming a unique synergistic advantage between the components. Each herb in the formula plays its specific role, works synergistically, and is indispensable.

[0006] Traditional Chinese medicine has a unique understanding of myocardial damage caused by sepsis. Ancient texts and works by physicians throughout history do not explicitly name or define sepsis. However, considering the clinical manifestations and pathogenesis of sepsis in modern medicine, it resembles the febrile diseases described in "typhoid fever" and "warm diseases," thus categorizing it under "exogenous febrile diseases," "wind-heat," and "warm toxins." Furthermore, because sepsis easily progresses to septic shock or multiple organ dysfunction, it can be classified under "syncope" and "collapse." Sepsis often affects organs such as the lungs, heart, liver, and kidneys. Based on its clinical manifestations, myocardial damage caused by sepsis can be classified under the traditional Chinese medicine categories of "chest pain," "heart pain," "palpitation," and "true heart pain."

[0007] Traditional Chinese medicine believes that the pathogenesis of myocardial damage in sepsis is often influenced by external pathogens, especially infections during the course of the disease. These external pathogens can cause stagnation of qi and blood, and imbalance of yin and yang. Since the human body is an integrated system, when invaded by external pathogens, the body's resistance to these pathogens struggles, leading to a deficiency of vital energy and affecting the functions of various organs. Sepsis mainly occurs due to the invasion of heat-toxin pathogens. The body's resistance weakens as the pathogens penetrate deeper, obstructing the flow of qi and blood, resulting in blood stasis, blockage of the meridians, and damage to various organs. The heart is the master of the five viscera and six bowels, governing the spirit, blood vessels, and all physiological activities of the body. When sepsis progresses to cardiac damage, it causes insufficient heart qi and damage to heart yang, weakening the heart's ability to transform qi and circulate blood, further aggravating the condition and ultimately leading to damage to the true organs and exhaustion of yang and yin. In summary, external pathogenic microorganisms (bacteria, viruses, etc.) invade the body, leading to deficiency of qi and blood, poor circulation, and stagnation of blood. The external pathogens then invade the heart through the meridians and blood vessels, causing the heart to lose its normal qi propulsion and nourishment, resulting in myocardial damage and impaired heart function.

[0008] Promoting blood circulation and removing blood stasis is one of the fundamental principles of traditional Chinese medicine in treating cardiovascular diseases. In the treatment of septic myocardial injury, drugs that promote blood circulation and remove blood stasis are often used to improve myocardial microcirculation and promote myocardial repair. Since the invasion of pathogenic factors is the main pathogenesis of septic myocardial injury, drugs that clear heat and detoxify also play an important role in treatment. Furthermore, pathogenic heat depletes qi and yin, leading to deficiency of qi and yin in the heart, malnourishment of the heart spirit, and insufficient blood flow. Therefore, it is necessary to add qi-tonifying and yin-nourishing drugs to replenish the qi and yin of the heart, support the body's vital energy, and promote myocardial cell repair and functional recovery. If the invasion of pathogenic factors is extremely severe, yang qi will decline, yin cold will prevail internally, and in severe cases, yin will be exhausted and yang will collapse. In such cases, methods to restore yang and consolidate the body will be added to the basic formula.

[0009] Based on the above analysis of the etiology, pathogenesis, and treatment principles of myocardial injury in sepsis, this invention supplements the basic formula of purging fire and detoxifying, promoting blood circulation and removing blood stasis with a formula of tonifying qi and restoring pulse, and restoring yang and consolidating the body, ultimately forming the unique compound formula of this invention. Specifically, the compatibility significance of the compound formula of this invention is as follows: The principal herbs are peach kernel and safflower. The combination of peach kernel and safflower has the effect of promoting blood circulation and removing blood stasis, dispersing the obstruction of the heart vessels; Coptis chinensis, gentian root, forsythia suspensa, salvia miltiorrhiza, and angelica sinensis are the assistant herbs. Coptis chinensis combined with gentian root treats both heart and liver fire, while the combination of forsythia suspensa and coptis chinensis enhances the heart-clearing and detoxifying power. The three herbs work together to purge fire and detoxify. In addition, salvia miltiorrhiza and angelica sinensis promote blood circulation, remove blood stasis, cool blood and nourish blood, so that removing blood stasis does not harm the body's vital energy; processed aconite, dried ginger, calcined dragon bone, immature bitter orange, and platycodon grandiflorus are the adjuvant herbs. Aconite root restores yang and rescues from collapse, dried ginger warms the middle and dispels cold, assisting aconite root in restoring yang and rescuing from collapse, while calcined dragon bone astringes and consolidates, preventing further dissipation of yang qi and yin fluids. The three combined can achieve the effects of restoring yang and rescuing from collapse, replenishing qi and consolidating the body. Bitter orange peel and platycodon root, one descending and one ascending, regulate qi, and when qi flows, blood flows. Chicken blood vine, rehmannia root, and prepared licorice root are the guiding herbs. Chicken blood vine invigorates blood and replenishes blood, while rehmannia root nourishes yin, cools blood, and stops bleeding. The two combined can help the principal herb resolve blood stasis without depleting blood. Prepared licorice root replenishes qi and harmonizes the middle, harmonizes the properties of the herbs, and assists ginseng and aconite root in restoring yang and restoring the pulse.

[0010] Peach kernel: Properties: Bitter, sweet, neutral. Channels entered: Heart, Liver, Large Intestine. Functions: Activates blood circulation and removes blood stasis, moistens the intestines and promotes bowel movement, relieves cough and asthma. Clinical applications: Various symptoms of blood stasis: dysmenorrhea, amenorrhea, postpartum abdominal pain due to blood stasis, abdominal masses (such as uterine fibroids), and swelling and pain from traumatic injuries. Often combined with safflower, angelica, and chuanxiong. Constipation due to intestinal dryness: Especially suitable for those with blood deficiency and fluid depletion accompanied by blood stasis. Lung abscess and intestinal abscess: Often combined with winter melon seed, coix seed, and rhubarb (such as in reed stem decoction and rhubarb and peony decoction). Cough and asthma: Used as an adjunct medicine to lower and drain lung qi.

[0011] Safflower: Properties: Pungent, warm. Channels entered: Heart and Liver. Functions: Activates blood circulation, regulates menstruation, disperses blood stasis, and relieves pain. Clinical applications: Gynecological blood stasis syndrome: dysmenorrhea, amenorrhea, postpartum lochia retention, abdominal pain due to blood stasis. It is an essential medicine for regulating menstruation in gynecology, often combined with peach kernel, angelica, and chuanxiong. Abdominal masses: masses caused by blood stasis. Chest pain, stabbing pain in the hypochondrium: angina pectoris in coronary heart disease, pain in the liver area, etc., often combined with danshen and chuanxiong. Traumatic injuries, swelling and pain due to blood stasis: often combined with sappanwood, frankincense, and myrrh. Dark-colored rashes (heat stagnation and blood stasis): such as measles, typhus, and other rash diseases with poor rash development and dark purple color.

[0012] Coptis chinensis: Properties: Bitter, cold. Channels entered: Heart, Spleen, Stomach, Liver, Gallbladder, Large Intestine. Functions: Clears heat and dries dampness, drains fire and detoxifies. Clinical applications: Damp-heat fullness, vomiting and acid regurgitation: Caused by damp-heat obstruction in the stomach and intestines, such as gastritis and dysentery (Xianglian Wan), often combined with Scutellaria baicalensis, dried ginger, and Pinellia ternata (Xiexin Tang type). Excessive heart fire: High fever, delirium, restlessness, insomnia, and sores on the mouth and tongue. Often combined with Scutellaria baicalensis and Gardenia jasminoides. Hematemesis and epistaxis due to blood heat: Combined with Scutellaria baicalensis and rhubarb (Xiexin Tang). Toothache due to stomach fire and diabetes (Zhongxiao): Clears stomach heat. Carbuncles, boils, eczema, and ear discharge: Drains fire and detoxifies, can be taken internally or applied externally (such as Coptis chinensis ointment). Vomiting due to liver fire invading the stomach (Zuojin Wan): Combined with Evodia rutaecarpa.

[0013] Gentian root: Properties: Bitter, cold. Channels entered: Liver, Gallbladder, Bladder. Functions: Clears heat and dries dampness, drains liver and gallbladder fire. Clinical applications: Damp-heat syndrome of the liver and gallbladder: distending pain in the hypochondrium, bitter taste in the mouth, swelling and itching of the genitals, yellow and foul-smelling vaginal discharge, turbid urine, jaundice. A key medicine for treating excess heat and damp-heat in the liver and gallbladder (Gentian root decoction for draining liver fire). Excessive heat in the liver meridian, leading to wind: high fever and convulsions, spasms of the hands and feet. Liver fire rising upwards: headache, red and swollen eyes, tinnitus and deafness.

[0014] Forsythia: Properties: Bitter, slightly cold. Channels entered: Lung, Heart, Small Intestine. Functions: Clears heat and detoxifies, reduces swelling and dissipates nodules, disperses wind-heat. Known as the "holy medicine for sores". Clinical applications: Carbuncles, boils, scrofula, and phlegm nodules: various heat-toxin sores in their early stages with redness, swelling, heat, and pain, or lymph node tuberculosis. Wind-heat exogenous disease, early stages of febrile diseases: fever, headache, thirst, sore throat (Yinqiao Powder). Heat entering the pericardium: high fever and delirium (Qinggong Decoction). Dysuria due to heat: clears heart fire and promotes urination.

[0015] Danshen (Salvia miltiorrhiza): Properties: Bitter, slightly cold. Channels entered: Heart and Liver. Functions: Activates blood circulation and regulates menstruation, removes blood stasis and relieves pain, cools blood and reduces swelling, relieves irritability and calms the mind. There is a saying that "one dose of Danshen decoction is as effective as Siwu Decoction" (referring to its blood-activating and menstruation-regulating effects). Clinical applications: Gynecological conditions: Menstrual disorders, dysmenorrhea, amenorrhea, postpartum abdominal pain due to blood stasis: an essential medicine for regulating menstruation, especially suitable for those with blood heat and blood stasis. Blood stasis causing heart pain, abdominal pain, masses, traumatic injuries: angina pectoris in coronary heart disease, hepatosplenomegaly, traumatic swelling. Sores and carbuncles: Utilizing its blood-cooling, blood-activating, and swelling-reducing effects. Febrile diseases: Irritability, delirium, palpitations, insomnia: Clears the heart, relieves irritability, and calms the mind.

[0016] Angelica sinensis: Nature and flavor: sweet, spicy, warm. Meridian tropism: liver, heart, spleen meridians. Efficacy: nourishing blood and regulating menstruation, promoting blood circulation to relieve pain, moistening intestines for defecation. It is known as the "holy medicine for nourishing blood" and the "essential medicine for regulating menstruation in gynecology". It also promotes blood circulation and removes blood stasis, and is known as the "qi medicine in blood". Clinical applications: various syndromes of blood deficiency: sallow complexion, dizziness and palpitations, etc. (Siwu Decoction). Irregular menstruation, dysmenorrhea, amenorrhea due to blood deficiency and blood stasis syndrome: it can both nourish blood and promote blood circulation to relieve pain. Cold pain in the abdomen, traumatic injury, numbness and pain in arthralgia: warming and dispersing cold congelation, promoting blood circulation to relieve pain (Angelica sinensis, ginger and mutton soup). Carbuncles and ulcers: nourishing blood and promoting blood circulation, expelling toxins, detumescence and promoting granulation. Constipation due to intestinal dryness caused by blood deficiency.

[0017] Prepared Rhizoma Coptidis: Nature and flavor: spicy, sweet, very hot; toxic (the toxicity is greatly reduced after processing). Meridian tropism: heart, kidney, spleen meridians. Efficacy: restoring yang to rescue from collapse, tonifying fire and assisting yang, dispelling cold and relieving pain. It is known as the "first-class medicine for restoring yang to rescue from collapse". Clinical applications (the toxicity of the processed product is reduced, focusing on warming yang): syndrome of yang collapse: cold sweating, cold limbs, feeble pulse (Sini Decoction). Yang deficiency syndrome: deficiency of kidney yang: aversion to cold and cold limbs, weakness and soreness of the waist and knees, impotence and spermatorrhea, cold uterus and infertility, frequent urination at night. Spleen-kidney yang deficiency: cold pain in the epigastrium and abdomen, loose stools (Fuzi Lizhong Pills). Heart yang deficiency: palpitations, shortness of breath, chest pain of angina pectoris. Inability to secure defensive yang: continuous sweating. Cold arthralgia syndrome: pain in the whole body joints due to wind-cold-damp arthralgia (especially good at treating severe pain of cold arthralgia).

[0018] Dry Ginger: Nature and flavor: spicy, hot. Meridian tropism: spleen, stomach, kidney, heart, lung meridians. Efficacy: warming the middle-jiao to dispel cold, restoring yang and promoting blood circulation, warming the lungs to resolve fluid-retention. Clinical applications: cold syndrome of the spleen and stomach: cold pain in the epigastrium and abdomen, vomiting and diarrhea (Lizhong Pills). Syndrome of yang collapse: often combined with Rhizoma Coptidis to enhance the effect of restoring yang (Sini Decoction). Cold-fluid-retention cough and asthma: aversion to cold and cold back, profuse and clear phlegm (Minor Green Dragon Decoction, Linggan Wuweijiangxin Decoction).

[0019] Calcined Os Draconis: Nature and flavor: sweet, astringent, flat. Meridian tropism: heart, liver, kidney meridians. Efficacy: after calcination, it focuses on astringing and consolidating, and when used raw, it is more inclined to calming the mind and suppressing hyperactive yang. Clinical applications (calcined Os Draconis): various syndromes of involuntary slipping: spermatorrhea, ejaculation, enuresis, frequent urination. Metrorrhagia and metrostaxis, leukorrhea, menorrhagia. Spontaneous sweating, night sweating. Eczema and pruritus, chronic ulceration of sores: externally used, it has the effect of astringing dampness and promoting granulation and generating flesh.

[0020] Fructus Aurantii: Nature and flavor: bitter, spicy, sour, slightly cold. Meridian tropism: spleen, stomach, large intestine meridians. Efficacy: regulating qi to soothe the middle, promoting qi movement to relieve distension. Its property is milder than Fructus Aurantii Immaturus, and it is more inclined to regulating qi in the chest and promoting qi movement to relieve distension. Clinical applications: syndrome of qi stagnation in the spleen and stomach: abdominal distension, indigestion, belching. Chest impediment, locked chest: distension and pain in the chest and hypochondrium. Prolapse of viscera (gastric prolapse, uterine prolapse, rectal prolapse): often combined with herbs that tonify qi and promote yang ascent such as Astragalus membranaceus, Bupleurum chinense, and Rhizoma Cimicifugae (modified Buzhong Yiqi Decoction).

[0021] Platycodon grandiflorus: Properties: Bitter, pungent, neutral. Channels entered: Lung channel. Functions: Clears lung heat, soothes the throat, eliminates phlegm, drains pus. It acts as a "carrier," carrying other medicines upwards. Clinical applications: Cough with excessive phlegm: Suitable for both cold and heat-related conditions, especially for those with cough, excessive phlegm, and chest tightness. Sore throat, loss of voice: Opens and clears lung qi, soothes the throat and restores voice. Lung abscess with purulent sputum: Drains pus and eliminates abscess (Platycodon grandiflorus decoction, Qianjin Weijing decoction). Urinary retention, constipation: Lifts the lid of the pot to open and clear lung qi to facilitate urination and defecation.

[0022] Chicken Blood Vine: Properties: Bitter, slightly sweet, warm. Channels Entered: Liver and Kidney channels. Functions: Activates blood circulation and nourishes blood, regulates menstruation and relieves pain, relaxes muscles and tendons. Clinical Applications: Irregular menstruation, dysmenorrhea, amenorrhea: Especially suitable for those with blood stasis or concurrent blood deficiency, as it both activates and nourishes blood. Rheumatic pain, numbness of limbs, paralysis: Activates blood circulation and unblocks channels. Blood deficiency and chlorosis: Has a certain blood-nourishing effect. Modern Applications: Leukopenia.

[0023] Rehmannia glutinosa: Properties: Sweet, cold. Channels entered: Heart, Liver, Kidney. Functions: Clears heat and cools blood, nourishes yin and generates fluids. Clinical applications: Heat entering the blood level: Fever worse at night, dry mouth, crimson tongue (Qingying Decoction). Blood heat causing bleeding: Hematemesis, epistaxis, hematuria, hematochezia, metrorrhagia (Xijiao Dihuang Decoction). Febrile diseases damaging yin: Thirst and excessive drinking, red tongue with little saliva (Yiwei Decoction). Yin deficiency with internal heat: Steaming fever, night sweats (Qinghao Biejia Decoction), diabetes.

[0024] Prepared licorice root: Properties: Sweet, neutral. Channels entered: Heart, Lung, Spleen, Stomach. Functions: Tonifies the spleen and replenishes qi, clears heat and detoxifies, resolves phlegm and relieves cough, alleviates spasms and pain, harmonizes other herbs. Clinical applications (prepared licorice root is more tonifying and harmonizing): Heart qi deficiency: palpitations, irregular pulse (Prepared licorice root decoction). Spleen and stomach qi deficiency: fatigue, poor appetite, loose stools (Four Gentlemen Decoction). Cough and asthma: Can be used regardless of cold or heat, deficiency or excess, with or without phlegm. Abdominal and limb spasms and pain: Peony and licorice root decoction. Carbuncles, boils, sore throat: Raw use is better. Harmonizing properties: In compound prescriptions, it can mitigate the harshness or toxicity of other herbs (such as aconite and rhubarb) and harmonize other herbs.

[0025] Specifically, the first aspect of the present invention provides a traditional Chinese medicine composition for preventing and treating myocardial damage caused by sepsis. The composition is composed of the following medicinal materials: peach kernel, safflower, coptis, gentian, forsythia, salvia miltiorrhiza, angelica sinensis, prepared aconite, dried ginger, calcined dragon bone, immature bitter orange, platycodon grandiflorus, chicken blood vine, rehmannia root, and prepared licorice root.

[0026] As a further explanation of the present invention, the composition comprises the following medicinal materials in parts by weight: 6-10 parts of peach kernel, 6-10 parts of safflower, 3-6 parts of coptis, 3-6 parts of gentian, 10-15 parts of forsythia, 10-15 parts of salvia miltiorrhiza, 6-12 parts of angelica sinensis, 3-8 parts of prepared aconite, 3-6 parts of dried ginger, 10-15 parts of calcined dragon bone, 6-10 parts of immature bitter orange, 6-10 parts of platycodon grandiflorus, 10-15 parts of chicken blood vine, 10-15 parts of rehmannia glutinosa, and 3-6 parts of prepared licorice.

[0027] As a further explanation of the present invention, the composition consists of the following medicinal materials in parts by weight: 8 parts peach kernel, 8 parts safflower, 5 parts coptis, 5 parts gentian, 12 parts forsythia, 12 parts salvia miltiorrhiza, 9 parts angelica sinensis, 6 parts prepared aconite, 5 parts dried ginger, 12 parts calcined dragon bone, 8 parts immature bitter orange, 8 parts platycodon, 12 parts chicken blood vine, 12 parts rehmannia root, and 5 parts prepared licorice root.

[0028] A second aspect of this invention provides a method for preparing a traditional Chinese medicine preparation for preventing and treating myocardial injury in sepsis, comprising the following steps: S1: Prepare a concentrated herbal paste from any of the above-mentioned herbal compositions for later use; S2: Add medically acceptable excipients to the concentrated Chinese medicine extract obtained in step S1 and prepare a Chinese medicine preparation using conventional preparation methods.

[0029] As a further explanation of the present invention, S1 specifically includes the following process: Weigh each herb in the herbal composition described above according to the proportion, add 8-10 times the total weight of the herbs in purified water and soak for 20-60 minutes, then decoct for 20-60 minutes, filter out the liquid, decoct 1-3 times in total, combine the multiple filtrates and concentrate under reduced pressure to a relative density of 1.10-1.30 to obtain concentrated herbal extract.

[0030] As a further explanation of the present invention, when decocting, prepared aconite should be decocted for 30-60 minutes first, and calcined dragon bone should be decocted for 15-30 minutes first.

[0031] The third aspect of the present invention provides a traditional Chinese medicine preparation for preventing and treating myocardial injury in sepsis, wherein the traditional Chinese medicine preparation is made by conventional preparation methods using the traditional Chinese medicine composition described in any one of the above-mentioned methods and clinically acceptable excipients.

[0032] As a further explanation of the present invention, the traditional Chinese medicine preparation is any one of decoction, powder, pill, granule, capsule, tablet, drop pill, syrup, or oral liquid.

[0033] The fourth aspect of the present invention provides the use of the traditional Chinese medicine composition described in any one of the above-mentioned methods, or the traditional Chinese medicine preparation prepared by any one of the above-mentioned methods, or the traditional Chinese medicine preparation described in any one of the above-mentioned methods, in the preparation of a medicament for treating myocardial injury in sepsis.

[0034] Compared with the prior art, the present invention has the following beneficial technical effects: This invention provides a self-formulated traditional Chinese medicine composition for the prevention and treatment of myocardial injury in sepsis. This traditional Chinese medicine composition, through multi-dimensional, dynamic, and holistic intervention, precisely targets the complex pathogenesis (intertwining of toxins, blood stasis, and deficiency) of myocardial injury in sepsis, achieving systemic regulation that is difficult to achieve with a single Western medicine drug.

[0035] This invention provides an in-depth analysis of the pathogenesis of myocardial injury in sepsis and formulates corresponding treatment principles based on these causes. Ultimately, it forms a unique combination of complementary advantages, where each herb in the formula performs its specific function, works synergistically, and is indispensable. Attached Figure Description

[0036] Figure 1 HE staining results of rat myocardial tissue in each group are shown. (a) HE staining results of sham-operated group, (b) HE staining results of model group, (c) HE staining results of positive control group, and (d) HE staining results of Example 2 group. Detailed Implementation

[0037] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0038] The Chinese medicinal materials used in the following examples and comparative examples are all commercially available processed products.

[0039] Example 1 This embodiment provides a traditional Chinese medicine composition for preventing and treating myocardial injury in sepsis. The composition consists of the following medicinal materials in parts by weight: 6 parts peach kernel, 6 parts safflower, 3 parts coptis, 3 parts gentian, 10 parts forsythia, 10 parts salvia miltiorrhiza, 6 parts angelica sinensis, 3 parts prepared aconite, 3 parts dried ginger, 10 parts calcined dragon bone, 6 parts immature bitter orange, 6 parts platycodon, 10 parts chicken blood vine, 10 parts rehmannia root, and 3 parts prepared licorice root.

[0040] Example 2 This embodiment provides a traditional Chinese medicine composition for preventing and treating myocardial injury caused by sepsis. The composition consists of the following medicinal materials in parts by weight: 8 parts peach kernel, 8 parts safflower, 5 parts coptis, 5 parts gentian, 12 parts forsythia, 12 parts salvia miltiorrhiza, 9 parts angelica sinensis, 6 parts prepared aconite, 5 parts dried ginger, 12 parts calcined dragon bone, 8 parts immature bitter orange, 8 parts platycodon, 12 parts chicken blood vine, 12 parts rehmannia root, and 5 parts prepared licorice root.

[0041] Example 3 This embodiment provides a traditional Chinese medicine composition for preventing and treating myocardial injury in sepsis. The composition consists of the following medicinal materials in parts by weight: 10 parts peach kernel, 10 parts safflower, 6 parts coptis, 6 parts gentian, 15 parts forsythia, 15 parts salvia miltiorrhiza, 12 parts angelica sinensis, 8 parts prepared aconite, 6 parts dried ginger, 15 parts calcined dragon bone, 10 parts immature bitter orange, 10 parts platycodon, 15 parts chicken blood vine, 15 parts rehmannia root, and 6 parts prepared licorice root.

[0042] Comparative Example 1: This comparative example provides a traditional Chinese medicine composition for preventing and treating myocardial injury caused by sepsis. The difference between this composition and Example 2 is that Coptis chinensis, Gentiana scabra, and Forsythia suspensa are removed from the traditional Chinese medicine composition.

[0043] Comparative Example 2: This comparative example provides a traditional Chinese medicine composition for preventing and treating myocardial injury caused by sepsis. The difference between this composition and Example 2 is that Danshen and Danggui are removed from the traditional Chinese medicine composition.

[0044] Comparative Example 3: This comparative example provides a traditional Chinese medicine composition for preventing and treating myocardial injury caused by sepsis. The difference between this composition and Example 2 is that the prepared aconite, dried ginger, and calcined dragon bone are removed from the traditional Chinese medicine composition.

[0045] Comparative Example 4: This comparative example provides a traditional Chinese medicine composition for preventing and treating myocardial injury caused by sepsis. The difference between this composition and Example 2 is that the herbs Citrus aurantium and Platycodon grandiflorus are removed from the traditional Chinese medicine composition.

[0046] Comparative Example 5: This comparative example provides a traditional Chinese medicine composition for preventing and treating myocardial injury caused by sepsis. The difference between this composition and Example 2 is that the chicken blood vine and rehmannia root are removed from the traditional Chinese medicine composition.

[0047] The traditional Chinese medicine compositions provided in the above embodiments and comparative examples were prepared into a dry extract powder for use in the following animal experimental verification process, specifically: Weigh each herb in the Chinese herbal composition provided in the above examples and comparative examples according to the proportions, add 8 times the total weight of the herbs in purified water and soak for 30 minutes. Then, decoct the prepared aconite root for 40 minutes until there is no numbing or spicy taste to reduce its toxicity. Decoction the calcined dragon bone for 20 minutes to fully extract its active ingredients. Finally, add the remaining herbs and decoct together for 40 minutes. Filter out the liquid. Then, add 8 times the total weight of the dregs in purified water to the dregs again and decoct for 20 minutes. Filter out the liquid. Combine the two filtrates and concentrate under reduced pressure to a relative density of 1.20 to obtain a concentrated Chinese herbal extract.

[0048] The concentrated herbal extracts prepared from the herbal compositions provided in the above embodiments and comparative examples are vacuum dried and ground into fine dry powder for later use.

[0049] The following animal experiments were used to verify the therapeutic effect of the traditional Chinese medicine composition provided in the embodiments and comparative examples of the present invention on a rat model of septic myocardial injury.

[0050] 1. Experimental materials 1.1 Laboratory Animals Purchase SPF-grade SD rats, male, 6 - 8 weeks old, with an average weight of (200 g ± 20 g). They were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., and the animal production license number is SCXK (Beijing) 2021 - 0006. Feeding conditions: Well-ventilated environment, indoor temperature at 20℃ - 26℃, relative humidity at 45% - 65%, natural sunlight exposure, and rats are free to eat, drink, etc. After being raised for 1 week and adapting to the environment, subsequent experiments were carried out.

[0051] 1.2 Experimental agents: The dry extract powder of traditional Chinese medicine prepared from the traditional Chinese medicine compositions provided in the above-mentioned examples and comparative examples.

[0052] Xuebijing Injection (National Medicine Approval Number Z20040033; produced by Tianjin Red Sun Pharmaceutical Co., Ltd.) with a concentration of 1 mg / mL.

[0053] 2. Experimental methods 2.1 Establishment, grouping, and administration of animal models Rats were anesthetized preoperatively with 3% isoflurane at an inhalation flow rate of 2 L / min. After being fully anesthetized, they were placed on the operating table, and a fixation device was used to ensure the stability of the animals. The abdomen of the rats was thoroughly disinfected with iodophor, and an incision of about 2 cm was made. The cecum was separated through the incision and washed with normal saline. The distal 1 / 3 of the cecum was ligated, and the ligated end was punctured twice with an 18-gauge needle to extrude the cecal contents. Then the cecum was returned to its original position, the abdominal cavity was closed, and after suturing the incision, subcutaneous injection of sterile normal saline (50 mL / kg) was performed for fluid resuscitation.

[0054] The rats were randomly divided into a positive control group, an Example 2 group, Comparative Example 1 - Comparative Example 5 groups, a sham operation group, and a model group, with 10 rats in each group. The positive control group, Example 2 group, Comparative Example 1 - Comparative Example 5 groups, and the model group were all constructed with a sepsis myocardial injury model according to the above method. The sham operation group also performed the same operations as above, but without cecal ligation and puncture.

[0055] The Example 2 group was given the dry extract powder of traditional Chinese medicine prepared from the traditional Chinese medicine formula provided in Example 2 3 days before the start of modeling. The Comparative Example 1 - Comparative Example 5 groups were given the dry extract powder of traditional Chinese medicine prepared from the traditional Chinese medicine formulas provided in Comparative Example 1 - Comparative Example 5 3 days before the start of modeling. The dry extract powder of traditional Chinese medicine in each of the above groups was administered by oral gavage at a dose of 5 g / kg, once every 12 hours; the positive control group was immediately treated with Xuebijing Injection after surgery, injected intraperitoneally at 10 mg / kg, once every 12 hours; the model group was given an equal volume of normal saline by oral gavage at the corresponding time. The mental state, activities, respiration, hair color, diet, water intake, urine and feces, and weight changes of rats in each group were observed. Blood was collected from the abdominal aorta 24 hours after the operation, the rats were sacrificed, and the hearts were collected for subsequent tests.

[0056] 2.2 Sample Collection and Processing Twenty-four hours later (based on previous experimental findings: myocardial injury is most severe 24 hours after cecal ligation), the final weight of rats in each group was recorded. After anesthesia, the rats were fixed on the operating table in a supine position. The abdominal cavity of the rats was opened along the midline of the abdomen, and the intestines and fat were separated with small forceps to expose the abdominal aorta. Blood was punctured and collected into a regular blood collection tube (approximately 4-5 ml). The sample was labeled, allowed to stand at room temperature for 30 minutes, and then centrifuged at 3000 rpm for 10 minutes. The supernatant was collected and stored at -80°C for later use.

[0057] After blood collection from rats, they were euthanized. The thoracic cavity was opened with sterile surgical scissors to expose the heart. The heart was cut at the root of the major blood vessels and immediately removed. After rinsing with physiological saline, the heart was cut along the long axis of the left ventricle to separate the left ventricular myocardial tissue. The tissue was fixed in 4% paraformaldehyde solution. Some of the myocardial tissue was dehydrated and embedded in paraffin to prepare sections for subsequent HE staining. The remaining myocardial tissue was stored in cryovials at -80°C for later use.

[0058] 2.3 Observation of pathological changes in myocardial tissue 2.3.1 Preparation of myocardial tissue samples (1) Fixation of myocardial tissue samples: The myocardial tissue samples were immersed in 4% paraformaldehyde solution for 24 hours.

[0059] (2) Dehydration: After rinsing the myocardial tissue block from the fixative, it is placed in alcohol with gradually increasing concentration gradients at room temperature for dehydration, namely: 70% (2h), 80% (2h), 90% (2h), 100% I (1h), 100% II (1h). The placement time should not be too long.

[0060] (3) Transparency: Place the myocardial tissue block in xylene solvent and treat for 30 minutes each time until the specimen becomes transparent.

[0061] (4) Embedding: The paraffin was melted in a 60°C incubator, and the myocardial tissue was placed in a model containing the dissolved paraffin and solidified after cooling.

[0062] (5) Slice preparation: The myocardial specimen paraffin block was cut into 5μm thin slices using a microtome, placed in a 60℃ incubator for 4h, and then dried on a glass slide.

[0063] 2.3.2 HE staining (1) Dewaxing and decolorization: After drying, the slices were first soaked in xylene I for 15 minutes, then in xylene II for another 15 minutes, until transparent. Then they were soaked in anhydrous ethanol (I, II) for 5 minutes each. After that, they were first soaked in 95% ethanol for 2 minutes, then in 85% ethanol for 2 minutes, then in 75% ethanol for 2 minutes, and finally soaked in distilled water for 2 minutes.

[0064] (2) Staining, dehydration and mounting: Immerse the sections in hematoxylin for 5 min, rinse with distilled water for 5 min. Immerse in 1% hydrochloric acid alcohol for 3 s, rinse with running water for 20 min. Immerse in 1% eosin staining solution for 3 min, rinse. Dehydrate the stained sections with ethanol in progressively increasing concentrations, then clear them with xylene, seal in neutral resin, and air dry at room temperature. Observe the staining under a microscope and take photographs for record-keeping.

[0065] 2.4 ELISA method for detecting TNF-α, IL-1β, IL-6, CK-MB, cTnL, and LDH levels After collecting and processing rat serum, the procedure was performed meticulously according to the ELISA kit instructions. After diluting the samples proportionally, the following steps were performed: 100 μL of each diluted antigen was added sequentially to the wells of an ELISA plate and incubated overnight at 4°C. The liquid in the wells was then removed by shaking off the excess liquid. The plate was washed three times with 200 μL PBST per well for 2 min each time. 100 μL of blocking buffer was added, and the plate was blocked at 37°C for 1 h. The liquid was then removed by shaking off the excess liquid. 200 μL PBST per well was washed three times, and 100 μL of the corresponding diluted antibody was added to each well. The plate was incubated at 37°C for 30 min. 200 μL PBST per well was washed three times again, and the diluted secondary antibody was added to react with the primary antibody. The reaction was carried out at 37°C for 30 min. The plate was washed five times with PBST, and 100 μL of TMB chromogenic solution was added to each well to initiate the enzyme reaction. The plate was incubated at 37°C for 15 min. 50 μL of enzyme stop solution was added to each well to stop the enzyme reaction. When the color changed from blue to yellow, the absorbance was read at 450 nm using an ELISA reader.

[0066] Use Excel software to draw a standard curve: the horizontal axis represents the concentration of the standard and the vertical axis represents the corresponding OD value. Draw the linear regression curve of the standard and use the curve equation to calculate the sample concentration.

[0067] 3. Statistical Analysis Statistical analysis was performed using SPSS 25.0 software. Normally distributed measurement data were expressed as mean ± standard deviation (x±s); all tests considered statistically significant with p<0.05 or p<0.01.

[0068] 4. Experimental Results 4.1 General condition of rats Rats in the sham-operated group showed better mental state, more stable breathing, alertness, normal activity, glossy fur, and normal diet, water intake, and bowel movements. Compared to the sham-operated group, rats in the model group exhibited decreased mental state, reduced activity, sluggishness, arched backs, rapid breathing, hair loss and dulling of the neck and tail base, and decreased food and water intake with increasing experimental time. In Example 2 and the positive control group, the above symptoms were all improved and alleviated to varying degrees compared to the model group.

[0069] 4.2 Pathological results of rat myocardial tissue Heart tissues from the Example 2 group, positive control group, model group, and sham-operated group were stained with hematoxylin and eosin (HE) according to the experimental method, and the morphological changes of the myocardial tissue were observed at 200x magnification. In the sham-operated group, cardiomyocytes were elongated spindle-shaped, neatly and tightly arranged, with normal oval-shaped nuclei visible in the center of the cells, which turned blue-purple after staining. The cytoplasm was pink, the tissue striations were relatively clear, and no obvious infiltrating inflammatory cells or pathological morphological changes were observed. In the model group, a large number of inflammatory cells infiltrated between cardiomyocytes, some cardiomyocytes were broken, and some myofibrils in the muscle fibers showed pathological changes such as dissolution. Compared with the model group, the positive control group and Example 2 group showed improvement in the above-mentioned pathological changes; specific results are shown in [the table below]. Figure 1 .

[0070] 4.3 Serum levels of TNF-α, IL-1β, and IL-6 in rats Table 1 shows the expression levels of TNF-α, IL-1β, and IL-6 in the serum of rats in each group.

[0071] Note: ## P<0.01 compared with the sham surgery group; Compared with the model group, P < 0.01; Compared with Example 2 group, P<0.05, Compared with Example 2 group, P<0.01, n=10.

[0072] As shown in Table 1, the serum levels of TNF-α, IL-1β, and IL-6 in the model group rats were significantly higher than those in the sham-operated group (P<0.01), indicating statistical significance. The serum levels of TNF-α, IL-1β, and IL-6 in the positive control group and Example 2 group were lower than those in the model group (P<0.01), indicating statistical difference. This demonstrates that the herbal composition provided by this invention significantly improves the levels of inflammatory factors in the serum of rats with septic myocardial injury. The serum levels of TNF-α, IL-1β, and IL-6 in Comparative Examples 1-5 were higher than those in Example 2 group (P<0.05), indicating statistical difference. This suggests that the absence of any single herb in the herbal composition of this invention significantly reduces the therapeutic effect of the herbal medicine.

[0073] 4.4 Serum levels of CK-MB, cTnI, and LDH in rats Table 2 shows the serum expression levels of CK-MB, cTnI, and LDH in each group of rats.

[0074] Note: ## P<0.01 compared with the sham surgery group; Compared with the model group, P < 0.01; Compared with Example 2 group, P<0.05, Compared with Example 2 group, P<0.01, n=10.

[0075] Changes in serum levels of CK-MB, cTnI, and LDH are key biochemical indicators for assessing the degree of myocardial cell damage. Their elevation directly reflects the pathological process of myocardial damage caused by sepsis. Therefore, this invention detected the levels of CK-MB, cTnI, and LDH in the serum of rats in each group. Specifically, as shown in Table 2, the serum levels of CK-MB, cTnI, and LDH in the model group rats were significantly higher than those in the sham-operated group (P < 0.01), indicating statistical significance. The serum levels of CK-MB, cTnI, and LDH in the positive control group and Example 2 group were lower than those in the model group (P < 0.01), indicating statistical difference. This demonstrates that the herbal composition provided by this invention has a significant regulatory effect on the levels of myocardial injury markers in the serum of rats with septic myocardial injury. The serum levels of CK-MB, cTnI, and LDH in Comparative Examples 1-5 were higher than those in Example 2 group, and the inter-group comparisons generally met the statistical requirement of P < 0.05 (only the cTnI content in Comparative Example 5 group did not meet the statistical requirement compared to Example 2 group). This indicates that the absence of a single herb in the herbal composition of this invention significantly reduces the therapeutic effect of the herbal medicine.

[0076] In summary, the above animal experiments have verified that the traditional Chinese medicine composition provided by this invention has a significant therapeutic effect on rats with sepsis-induced myocardial injury. At the same time, the traditional Chinese medicine composition provided by this invention has a significant synergistic effect. When certain individual traditional Chinese medicines are removed, the final therapeutic effect is not ideal, thus demonstrating the unique compatibility advantages of the traditional Chinese medicine preparation provided by this invention.

[0077] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A traditional Chinese medicine composition for preventing and treating myocardial injury caused by sepsis, characterized in that, The composition consists of the following medicinal materials: peach kernel, safflower, coptis, gentian, forsythia, salvia miltiorrhiza, angelica sinensis, prepared aconite, dried ginger, calcined dragon bone, immature bitter orange, platycodon grandiflorus, chicken blood vine, rehmannia glutinosa, and prepared licorice.

2. The traditional Chinese medicine composition for preventing and treating myocardial injury in sepsis as described in claim 1, characterized in that, The composition consists of the following medicinal materials in parts by weight: 6-10 parts peach kernel, 6-10 parts safflower, 3-6 parts coptis, 3-6 parts gentian, 10-15 parts forsythia, 10-15 parts salvia miltiorrhiza, 6-12 parts angelica sinensis, 3-8 parts prepared aconite, 3-6 parts dried ginger, 10-15 parts calcined dragon bone, 6-10 parts immature bitter orange, 6-10 parts platycodon, 10-15 parts chicken blood vine, 10-15 parts rehmannia root, and 3-6 parts prepared licorice root.

3. The traditional Chinese medicine composition for preventing and treating myocardial injury in sepsis as described in claim 1, characterized in that, The composition consists of the following medicinal materials in parts by weight: 8 parts peach kernel, 8 parts safflower, 5 parts coptis, 5 parts gentian, 12 parts forsythia, 12 parts salvia miltiorrhiza, 9 parts angelica sinensis, 6 parts prepared aconite, 5 parts dried ginger, 12 parts calcined dragon bone, 8 parts immature bitter orange, 8 parts platycodon, 12 parts chicken blood vine, 12 parts rehmannia root, and 5 parts prepared licorice root.

4. A method for preparing a traditional Chinese medicine preparation for preventing and treating myocardial injury caused by sepsis, characterized in that, Includes the following steps: S1: Prepare a concentrated herbal extract from the herbal composition according to any one of claims 1-3 for later use; S2: Add medically acceptable excipients to the concentrated Chinese medicine extract obtained in step S1 and prepare a Chinese medicine preparation using conventional preparation methods.

5. The method for preparing the traditional Chinese medicine preparation for preventing and treating myocardial injury in sepsis as described in claim 4, characterized in that, S1 specifically includes the following process: Weigh each herb in the traditional Chinese medicine composition according to any one of claims 1-3 according to the proportion, add 8-10 times the total weight of the herb in purified water and soak for 20-60 minutes, then decoct for 20-60 minutes, filter out the decoction, decoct 1-3 times in total, combine the multiple filtrates and concentrate under reduced pressure to a relative density of 1.10-1.30 to obtain a concentrated traditional Chinese medicine extract.

6. The method for preparing the traditional Chinese medicine preparation for preventing and treating myocardial injury in sepsis as described in claim 5, characterized in that, When decocting, prepared aconite root should be decocted for 30-60 minutes first, and calcined dragon bone should be decocted for 15-30 minutes first.

7. A traditional Chinese medicine preparation for preventing and treating myocardial injury caused by sepsis, characterized in that, The traditional Chinese medicine preparation is made using any one of the traditional Chinese medicine compositions according to claims 1-3 and clinically acceptable excipients in a conventional formulation manner.

8. The traditional Chinese medicine preparation for preventing and treating myocardial injury in sepsis as described in claim 7, characterized in that, The traditional Chinese medicine preparation is any one of the following: decoction, powder, pill, granule, capsule, tablet, drop pill, syrup, or oral liquid.

9. The use of the traditional Chinese medicine composition according to any one of claims 1 to 3, or the traditional Chinese medicine preparation obtained by the preparation method according to any one of claims 4 to 5, or the traditional Chinese medicine preparation according to any one of claims 6 to 7, in the preparation of a drug for treating myocardial injury caused by sepsis.

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