Application of loss-increasing real-person viscera-nourishing decoction in preparation of medicine for treating critically ill antibiotic-associated diarrhea

Abstract

The invention relates to the field of traditional Chinese medicine application, and discloses application of a loss-increasing real-person viscera-nourishing decoction in preparation of a medicine for treating critically ill antibiotic-associated diarrhea, and the loss-increasing real-person viscera-nourishing decoction comprises the following active ingredient raw materials in parts by weight: 13-17 parts of ginseng, 13-17 parts of charred angelica sinensis, 18-22 parts of roasted rhizoma atractylodis macrocephalae, 13-17 parts of myristica fragrans, 5-7 parts of cinnamon and 8-12 parts of honey-fried licorice root. , 18-22 parts of parched white peony root, 8-12 parts of roasted radix aucklandiae, 8-12 parts of roasted fructus chebulae and 18-22 parts of pomegranate rind. The loss-increasing real-person viscera-nourishing decoction shows a good curative effect in the treatment process of antibiotic-related diarrhea of critical patients, also shows a good curative effect in the aspects of improving the gastrointestinal function and the overall health condition of the patients, is relatively low in recurrence rate, has good safety, and is suitable for clinical application. The compound can be effectively used for preparing the medicine for treating the critically ill antibiotic-associated diarrhea and treating the critically ill antibiotic-associated diarrhea.

Description

Technical Field

[0001] The invention relates to the application field of traditional Chinese medicine, and in particular to the application of Zengsun Zhenren Yangzang Decoction in the preparation of a medicine for treating critical antibiotic-associated diarrhea. Background Art

[0002] Antibiotic Associated Diarrhea (AAD) refers to a type of diarrheal symptom that occurs after taking antibiotics. This disease usually occurs after the start of antibiotic treatment and is a common type of drug-induced diarrhea. The symptoms of this disease can range from mild, systemic symptoms to more severe pseudomembranous colitis. In severe cases, toxic megacolon, intestinal perforation, and even death may occur. In recent years, with the increasing frequency of antibiotic use, many patients with serious infections have been successfully treated, but this is accompanied by serious abuse of antibiotics, an increasing number of drug-resistant strains, and a gradual increase in the incidence of antibiotic-associated diarrhea. According to foreign literature reports, the prevalence of this disease is 5% to 35%. Domestic reports are 7% to 29%. Critically ill patients are a high-risk group for hospital infection, and long-term bed rest has a certain impact on the gastrointestinal function of patients. A scholar investigated 981 critically ill patients, and the results showed that gastrointestinal infections accounted for 28.76% of the total hospital infection rate, among which patients with antibiotic-associated diarrhea accounted for 77.27% of gastrointestinal infections. If a patient develops antibiotic-associated diarrhea, his or her hospitalization time may be prolonged, and may cause serious complications and lead to death.

[0003] Modern research suggests that the pathogenesis of antibiotic-associated diarrhea involves the combined effects of multiple factors. The main factors include the imbalance of normal intestinal flora caused by antibiotics, the disturbance of intestinal carbohydrate and bile acid metabolism, and the direct impact of antibiotics on the normal physiological function of the intestine. Gastrointestinal dysfunction is an important factor in the high incidence of AAD in critically ill patients.

[0004] The impact of antibiotics on intestinal flora: The main function of antibiotics is to destroy the protective barrier of the intestine and disrupt the normal microbial flora, resulting in the dominance of foreign bacteria, conditional pathogens and resistant symbiotic bacteria, which is the main cause of AAD. Pathogenic bacteria can destroy the normal physical and chemical environment of the intestine through enterotoxins, reduce the activity of functional enzymes in cells, and affect the balance of intestinal microecology and normal physiological functions. The use of antibiotics disrupts the balance of beneficial flora in the intestine and weakens the body's natural defense against pathogens such as Clostridium perfringens and Staphylococcus aureus. This interference can lead to damage to the normal physiological functions of the intestine, and then complications of the digestive system such as diarrhea and colitis.

[0005] Effects of antibiotics on the intestinal barrier: The use of antibiotics may disrupt the metabolism of carbohydrates and bile acids in the intestine. In addition, the normal metabolic activity of colonic epithelial cells also depends on the integrity of the intestinal physical barrier and its ability to recover quickly after damage. Under normal physiological conditions, colonic epithelial cells rely on short-chain fatty acids produced by fermentation of normal intestinal flora to obtain the energy required for their physiological metabolism. The use of antibiotics will not only significantly reduce the number of normal flora in the intestine, but also interfere with the fermentation process of these flora, thereby affecting the production of polysaccharides and short-chain fatty acids, which in turn leads to damage to the normal physical barrier of the intestine. In addition, since a large amount of polysaccharides accumulate in the intestine and cannot be effectively absorbed, patients will experience symptoms of osmotic diarrhea.

[0006] High-incidence factors of AAD in critically ill patients: Critically ill patients often have serious infections or are at high risk of infection. Under the dual blow of disease and invasive operations, the intestines are the first to be affected. Clinically, such patients often have varying degrees of gastrointestinal dysfunction. In this case, the patient's gastrointestinal motility is reduced, the secretion of digestive juices is reduced, and even necrosis and shedding occur. The intestinal mucosa's ability to absorb nutrients is reduced, which aggravates the damage to the intestinal barrier, reduces the intestinal immune function, and causes various pathogenic bacteria to multiply, thus forming endogenous infection, which in turn causes dehydration and shock in patients, leading to MODS and increasing the mortality rate.

[0007] Current status of AAD treatment: In the treatment of antibiotic-associated diarrhea, generally speaking, it is necessary to stop the currently used antibiotics or replace them with antibacterial drugs with lower risks. In addition, in conventional treatment, it is necessary to correct fluid loss and infuse fluids to maintain water and electrolyte balance. During treatment, scopolamine-type antispasmodics and loperamide-like drugs should be avoided as much as possible to avoid endotoxin accumulation. For antibiotic-associated diarrhea with Clostridium difficile infection, metronidazole and vancomycin are commonly used drugs for the treatment of such conditions. However, since these drugs cannot eliminate the spore form of bacteria and may destroy the beneficial flora in the intestine, the recurrence rate after treatment is relatively high. In recent years, the use of microbial preparations such as probiotics to treat or prevent AAD has become the focus of research. At present, microbial preparations for the adjuvant treatment of AAD mainly include the following categories: Lactobacillus acidophilus, Lactobacillus bulgaricus, Streptococcus thermophilus, and Saccharomyces boulardii, etc. They can promote the recovery of beneficial intestinal flora and effectively control the proliferation of pathogens, thereby helping to alleviate clinical symptoms.

[0008] Current status of treatment of critical AAD: Western medicine treatment of critical antibiotic-associated diarrhea needs to be further explored. The current treatment usually adds antidiarrheal agents, probiotics, etc. while satisfying the treatment of the patient's underlying disease. Since gastrointestinal failure is one of the causes of AAD in critically ill patients, improving gastrointestinal function in critically ill patients, supplementing active bacterial preparations such as lactobacillus, and using enteral nutrition support to improve the body's immunity can prevent and treat AAD to a certain extent. For patients with impaired gastrointestinal function, it is difficult for exogenous live bacteria to spread quickly throughout the intestine, so actively restoring gastrointestinal function can improve the treatment effect more than relying solely on traditional treatment methods. From the relevant literature research, since critically ill patients often have gastrointestinal dysfunction, when they have antibiotic-associated diarrhea, adjusting antibiotics and giving microecological preparations to improve gastrointestinal function are helpful to improve the condition. In addition, allogeneic fecal microbiota transplantation (FMT) can also significantly improve the intestinal flora disorder of patients, but because it contains multiple components such as bacteria, fungi, and viruses, the specific risk source is difficult to clearly identify, so its safety is still controversial.

[0009] In summary, although modern research has proven the mechanistic relationship between critically ill patients and antibiotic-associated diarrhea, there is a problem of singleness in the treatment drugs and treatment plans, resulting in poor efficacy. In addition, the critically ill patients are in a critical condition, and changing antibiotics sometimes cannot cover the original pathogens. The simple symptomatic supportive treatment or the use of microecological preparations has no significant clinical effect. Therefore, in the clinical treatment of Western medicine, how to improve the effect of drug treatment, expand the scope of drug treatment, cover the accompanying symptoms, and control the clinical symptoms of this disease while ensuring the treatment of the basic disease is the current research direction.

[0010] TCM's understanding of critical antibiotic-associated diarrhea: TCM does not have the concept of "antibiotic-associated diarrhea". According to its clinical symptoms, it can be classified as "diarrhea". The location of diarrhea is in the spleen and stomach, which is closely related to the liver and kidneys. The pathogenesis is mainly related to the spleen and stomach's failure to ascend and descend and the disorder of transportation and transformation. Chen Wuzhe's "Sanyin Jiyi Bingzheng Fanglun" established the name of "diarrhea" in later generations. As early as in "Suwen", the main causes and pathogenesis of diarrhea were elaborated in detail, such as "sudden diarrhea and urgency are all related to heat", "cold air invades the small intestine...so there is abdominal pain after diarrhea", "wetness leads to wet diarrhea", pointing out that diarrhea is related to three factors: cold, dampness and heat. Shen Jinao, a medical scientist in the Qing Dynasty, also mentioned in his book "Xizhu of the Origin of Miscellaneous Diseases·Origin of Diarrhea" that although diarrhea may be caused by different factors such as wind, cold, heat, and deficiency, most of them are related to dampness. Wang Qingren of the Qing Dynasty pointed out in his book "Correcting Errors in Medicine" when discussing the relationship between blood stasis and diarrhea: "If the diarrhea lasts for a long time, it must be caused by blood stasis." It can be seen that the causes of diarrhea are generally closely related to cold, heat, deficiency, dampness, and blood stasis, but dampness is the main cause. According to traditional Chinese medicine theory, antibiotics are usually classified as bitter and cold products that purge fire. Long-term or excessive use of such drugs will damage the spleen and stomach yang and aggravate diarrhea symptoms. If the condition does not heal for a long time, it may also affect the kidneys, causing kidney yang deficiency, and clinical manifestations are diarrhea at dawn.

[0011] Understanding of etiology and pathogenesis: The pathogenesis of antibiotic-associated diarrhea in critical illness is generally closely related to "deficiency of vital energy and invasion of pathogenic factors", "spleen deficiency and instability", "deficiency of kidney yang", and "external accumulation of dampness and toxins". The deficiency of vital energy in critically ill patients is an internal factor in the onset and progression of the disease, while the invasion of exogenous pathogens, especially the "drug toxicity" caused by antibiotics, is an external cause of the disease. Throughout the course of the disease, "dampness" is always present and plays an important role. From the perspective of pathogenesis, "deficiency" is the root of the disease, while "dampness" and "toxins" are its manifestations. These three are intertwined and together lead to the occurrence of this disease.

[0012] The Ancient and Modern Medical Mirror states: "Diarrhea is caused by the spleen and stomach being injured by eating raw and cold food, or by summer heat, dampness, wind and cold." The pathogenesis of diarrhea is usually due to external or internal injuries that lead to dysfunction of the spleen and stomach, which cannot normally transport and transform water and dampness, and the sinking of clear qi, causing diarrhea. If the condition is not treated properly, it may continue to not heal, and the long-term illness may affect the kidneys, eventually leading to the decline of fire and the inability to warm the middle earth, which will worsen the condition. The Jingyue Complete Book of Diarrhea states: "The kidney is the gate of the stomach, and it opens the orifices of the two yins... which makes people have endless diarrhea." The kidney is responsible for sealing and storing, and controls the front and back two yins. If the kidney qi is weak, its sealing and storing function will be damaged, resulting in poor closing, and thus loose stools. The kidney is the innate foundation. If the fire of the gate of life is weak and the kidney yang is insufficient, the spleen yang will not be able to continue, and the transportation and transformation function will be abnormal, causing dampness to stay and accumulate in the body, and the accumulation of dampness will become toxic, resulting in long-term diarrhea. Dampness and toxicity are the key to the prolongation of this disease. Deficiency and coldness of the spleen and kidneys will lead to disorders in their functions of transporting and transforming and controlling water, making dampness and toxicity more difficult to eliminate. The two form a vicious cycle, putting the patient in a state of mixed good and evil.

[0013] Conventional treatment methods in modern medicine can easily promote dampness and damage Yang. Antibiotics are bitter, cold and heat-clearing products. While fighting infection, they can also directly damage Yang. Most critically ill patients are elderly people. The Yang of the elderly is already weak and the function of their internal organs is low. The most obvious is the exhaustion of the Yang of the spleen and kidney. The long-term use of antibiotics further aggravates the loss of the Yang of the spleen and kidney, leading to an imbalance in water metabolism, accumulation in the intestines, and then causing diarrhea. Zheng Ya and other scholars pointed out that the three elements of deficiency, toxicity and dampness play a key role in the pathogenesis of this disease. Among them, "deficiency" refers to the weakness of the body's positive energy, "toxicity" refers to the characteristics of antibiotics and their negative effects on the human body, and "dampness" is the result of the body's pathological reaction after the action of antibiotics. They affect each other and cross-harm each other.

[0014] The "Guidelines for Clinical Research of New Chinese Medicines" classifies antibiotic-associated diarrhea into four common syndrome types: damp-heat syndrome, cold-damp syndrome, spleen-stomach deficiency syndrome, and spleen-kidney yang deficiency syndrome. Yuan Ling counted the syndrome types of 60 patients with antibiotic-associated diarrhea and found that spleen-kidney yang deficiency syndrome and spleen-stomach deficiency syndrome were the most common. Among patients of all ages, young patients often had damp-heat syndrome, middle-aged patients often had spleen-stomach deficiency syndrome, and elderly patients were mainly spleen-kidney yang deficiency syndrome. Liu Lin and other researchers conducted a retrospective analysis of 216 patients with severe infections and found that 81 of these patients had antibiotic-associated diarrhea, with an incidence rate of 37.5%. Among the 81 cases of antibiotic-associated diarrhea, 24 had blood stasis syndrome; 52 cases had spleen deficiency and phlegm-dampness syndrome, of which 16 cases were combined with blood stasis syndrome, accounting for 30.77%. Blood stasis syndrome accounts for 29.63% of the distribution of antibiotic-associated diarrhea syndromes, second only to spleen deficiency and phlegm-dampness syndrome (64.20%), and is an important component of the distribution of antibiotic-associated diarrhea syndromes. In traditional Chinese medicine theory, antibiotics are classified as "poisonous evils". For people with weak constitutions, they cannot withstand strong drug power. Therefore, after using antibiotics, the toxicity of the drugs may damage the intestinal veins, causing dampness and cold toxins to stagnate in the intestines. Through epidemiological research methods, the investigation found that spleen and kidney yang deficiency and spleen and stomach weakness syndromes occupy an important position in all syndromes. Yuan Geng et al. observed 70 diarrhea patients in the intensive care unit of Guang'anmen Hospital of China Academy of Chinese Medical Sciences and found that 41 cases were mixed with cold and heat, and clear and turbid mixed, accounting for 58.6%; 16 cases were spleen and kidney yang deficiency, accounting for 22.8%; and 13 cases were spleen and stomach damp-heat syndrome, accounting for 18.6%. Among the patients with spleen and kidney yang deficiency, 11 had an APACHE II score of ≥20, accounting for 68.8%, and 9 died, accounting for 56.2%, which was the syndrome with the highest mortality rate. The syndrome differentiation of critical antibiotic-associated diarrhea has not yet been completely unified, but from the clinical and research of the above experts and scholars, it can be found that excess syndrome is mostly related to damp heat, phlegm dampness, and blood stasis, while deficiency syndrome is mostly caused by yang deficiency and qi deficiency.

[0015] Zheng Cailian and others used the principle of warming and tonifying the spleen and kidney as treatment, and used the modified Si Shen Decoction to specifically treat the spleen and kidney yang deficiency syndrome of antibiotic-associated diarrhea in the ICU. This prescription can not only effectively enhance the patient's immunity, but also adjust the balance of intestinal flora and increase the number of beneficial bacteria. Through these effects, the patient's clinical symptoms were significantly relieved. At the same time, the experimental results showed that this prescription also helped to reduce the recurrence rate of the disease. Li Cong and others used the modified Gegen Qinlian Decoction to treat patients with spleen and kidney yang deficiency syndrome of antibiotic-associated diarrhea. This prescription invigorates the spleen and kidney, clears heat and purges fire, detoxifies and stops diarrhea. The results showed that compared with the control group, the T lymphocyte level of the treatment group patients showed a significant advantage. At the same time, in terms of the severity of diarrhea, TCM symptoms and APACHE II scores, the patients in the treatment group showed lower values, showing a better treatment effect. The overall effective rate was also higher than that of the control group, which further demonstrated that the modified Gegen Qinlian Decoction has a significant effect in enhancing the patient's immune function and improving diarrhea symptoms, and has good clinical application potential. Zhang Guangyu et al. treated patients with antibiotic-associated diarrhea with spleen and stomach deficiency and cold syndrome by strengthening the spleen and replenishing qi, removing dampness and detoxifying. The results showed that the observation group was superior to the control group in the scores of the main symptoms and secondary symptoms, as well as the scores of spleen and stomach deficiency and cold syndrome. In addition, the number of cocci and enterococci in the fecal samples of the observation group was also less than that of the control group, while the number of bifidobacteria and lactobacilli was more than that of the control group. This shows that in patients with spleen and stomach deficiency and cold syndrome caused by antibiotic-associated diarrhea, the treatment of Shenling Baizhu powder on the basis of taking probiotics can further relieve symptoms and improve the treatment effect. This treatment method can also help enhance the body's immune function, adjust the balance of intestinal flora, and promote the recovery of the intestinal mucosal barrier.

[0016] Huang Xuxia et al. believed that the mixed cold and heat is the key to the pathogenesis of elderly patients with antibiotic-associated diarrhea. Elderly patients often have infectious diseases, and most of them show typical fever symptoms such as redness, swelling, heat and pain. Since antibiotics are bitter and cold drugs, they may damage the body's yang. Long-term illness, improper treatment or repeated illness are more likely to damage the liver, spleen and kidney, leading to the mutual appearance of deficiency and excess, and the mixed cold and heat. Among them, the upper heat and lower cold are more common. In the treatment process, attention should be paid to the use of warming and clearing, that is, to reconcile the cold and hot qi in the body. Wumei Pills are used to take into account both deficiency and excess, warming yang and dispersing cold, and clearing heat and drying dampness, and the two are parallel without being too rigid and dry. While clearing dampness and heat, attention should also be paid to protecting yang and stomach qi to ensure the comprehensiveness of treatment. Zheng Ya et al. believed that spleen and kidney yang deficiency is the fundamental internal cause of antibiotic-associated diarrhea in elderly patients, which constitutes the basis for the occurrence of the disease, while drug toxicity and internal moisture are important external pathogenic factors and the direct cause of the disease. Treatment should follow the principles of "strengthening the body's resistance and eliminating pathogenic factors" and "treating both the symptoms and the root causes" of traditional Chinese medicine, mainly by strengthening the spleen and warming the yang to enhance the body's own resistance, while supplemented by therapies to eliminate dampness and detoxify to remove pathogenic factors. This comprehensive treatment method provides a theoretical basis for the treatment of antibiotic-associated diarrhea in the elderly with traditional Chinese medicine, and conducts exploratory research on improving clinical treatment effects.

[0017] It can be seen that TCM treatment of critical antibiotic-associated diarrhea is based on a holistic view, treating patients according to syndrome differentiation, and is more individualized. In clinical practice, various doctors have summarized rich clinical experience from ancient times to the present, put forward unique personal insights, and developed distinctive treatment plans, which have shown good efficacy in taking into account the patient's underlying diseases and improving diarrhea symptoms.

[0018] The inventor of this application, Professor Chen Mingxian, found in the process of clinical diagnosis and treatment that as the population structure of my country gradually ages, the elderly account for a relatively high proportion of critically ill patients who are hospitalized for long-term treatment. In view of the physiological characteristics of the elderly population and the understanding of the effects of antibiotics in traditional Chinese medicine, it is generally believed that the symptoms of these patients are mainly spleen and kidney deficiency and cold syndrome. Due to long-term illness, the body is weak and the spleen and kidney are deficient, and antibiotics are mostly bitter and cold in nature, which further damages the yang qi of the spleen and kidney, and the yin and cold are dominant, the water and moisture cannot be transformed, and the intestines are not clear and turbid. It is easy to accumulate turbid toxins in the winding part of the intestine, which causes diarrhea, abdominal distension, fever and other symptoms.

[0019] 1. Causes

[0020] 1.1 External invasion

[0021] "Ming Yi Za Zhu" says: "During summer and autumn, dampness and heat are rampant, and watery diarrhea occurs violently." "Ling Shu·Shi Chuan" points out: "If there is cold in the stomach and heat in the intestines, there will be bloating and diarrhea." It can be seen that a variety of factors such as cold, dampness, and summer heat can cause diarrhea. The spleen likes dryness and hates dampness. When dampness invades the human body, it is easy to damage the spleen and stomach, causing dysfunction of the spleen and stomach transportation and transformation, thus causing diarrhea. The ancient saying: "There is no diarrhea without dampness", which means that although diarrhea can be caused by a variety of reasons such as wind, cold, heat, and dampness, dampness is particularly common among them.

[0022] 1.2 Insufficient endowment

[0023] The spleen and stomach are the foundation of the acquired constitution and the source of qi and blood. After a serious illness or a long-term illness, the spleen and stomach functions are often damaged and become weak, unable to effectively decompose water and grain and transport water and moisture. This leads to endogenous moisture, which mixes down and eventually causes diarrhea. In addition, the spleen and kidney are closely related, and the transportation and transformation of spleen qi requires the warmth of kidney yang. For the elderly and weak, the deficiency of kidney yang makes it impossible for them to effectively warm the spleen and stomach, which in turn affects the transportation and transformation function of the spleen and stomach. In this case, they are more likely to have prolonged diarrhea or symptoms of early morning diarrhea.

[0024] 2. Pathogenesis

[0025] The disease is based on spleen and kidney yang deficiency, and the drug toxicity is the symptom of latent evil. Antibiotics are bitter and cold, which can purge fire, and bitterness can turn dryness into injury to yin, and coldness can block the qi mechanism, leading to abnormal circulation of qi, blood, and body fluids, affecting the functions of the internal organs, and producing pathological products such as phlegm, dampness, and toxins. Long-term, large-scale, and irrational use of antibiotics will damage spleen yang, and fail to transport and transform the essence of water and grain. Water and grain are mixed in the intestines, and over time, dampness accumulates and becomes toxic. Due to long-term illness and physical weakness, dysfunction of the five internal organs will further aggravate the accumulation and stagnation of water, dampness, and drug toxins in the intestines, seriously affecting the normal conduction function of the large intestine, thereby aggravating diarrhea symptoms. Most of the critically ill patients are elderly people. The "positive energy" of the elderly is already weak before they are sick. In addition, due to long-term illness, kidney yang is gradually depleted, resulting in the weakening of the fire of the gate of life, which cannot warm the spleen and stomach. This makes the spleen lose its warm nourishment, and its transportation and transformation function fails, which makes it more likely to cause diarrhea symptoms. The pathogenesis of this disease is ultimately due to the deficiency of vital energy, the presence of hidden evil in the body, and the toxicity of antibiotics. The three factors are mixed together to form the disease. Most of them are caused by internal injuries and long-term illness, which leads to spleen and stomach dysfunction, turbid toxins accumulating in the middle jiao and coldness in the lower jiao.

[0026] 2.1 Spleen and stomach deficiency and coldness

[0027] The Jingyue Complete Works, Xiexie, states: "The root of diarrhea is all due to the spleen and stomach... which causes the combined filth to descend and diarrhea to occur." The spleen and stomach are organs that corrode water and food and transport and transform the essence, and the spleen's kinetic energy for transportation and transformation depends entirely on sufficient yang. If fatigue, internal injuries, or repeated diarrhea occur, the spleen's yang is insufficient, and its ability to corrode water and food and transport and transform the essence will be impaired, causing water and food to stagnate in the body, with no clear or turbid separation. In this way, water and dregs are mixed together, which leads to diarrhea symptoms. Regardless of the type of diarrhea, its internal cause is usually closely related to spleen weakness, and its root is always related to spleen and stomach dysfunction.

[0028] 2.2 Kidney Yang Deficiency

[0029] The Clinical Guide Medical Case states: "Morning diarrhea is caused by the kidneys." Insufficient rise of kidney yang and weak kidney qi are the root causes of qi disorder and wide opening of the "stomach gate." The Treatise on Kidney Diarrhea in Classification of Symptoms and Treatments states: "Diarrhea caused by deficiency of true yang in the kidneys occurs several times at dawn or at dawn." Long-term illness or prolonged uncured diarrhea will further damage kidney yang. Kidney yang is also called "primordial yang" and is closely related to the yang qi of the whole body. When kidney yang is insufficient, spleen yang will also become weak. Insufficient spleen yang and loss of control will lead to diarrhea, which is often manifested as diarrhea several times at dawn.

[0030] Zhenren Yangzang Soup comes from the Taiping Huimin Hejijufang in the Song Dynasty. It is also known as "Chunyang Zhenren Yangzang Soup". Composition: ginseng, angelica (remove the stem), white atractylodes (roasted) 6 qian (6 grams each), nutmeg (wrapped in flour, simmered) half a liang (8 grams), white peony 1 liang 6 qian (12 grams), terminalia chebula (remove the core) 1 liang 2 qian (9 grams), cinnamon (remove the rough skin), roasted licorice 8 qian (6 grams each), costusroot (no fire) 1 liang 4 qian (3 grams), poppy shell (remove the stalk and calyx, roasted with honey) 3 liang 6 qian (9 grams). Indications: chronic diarrhea, cold in the middle jiao, excessive diarrhea. Slipping and prolapse, even prolapse of the anus, abdominal pain likes warmth and pressure. Or red and white diarrhea, or pus and blood in the stool, excessive day and night, tenesmus, fatigue and poor appetite, pale tongue with white fur, slow and thin pulse. It is mainly used clinically to treat chronic diarrhea, chronic colitis, ulcerative colitis, anal swelling, etc. However, there is no public report on the use of Zhenren Yangzang Decoction in the preparation of drugs for the treatment of critical antibiotic-associated diarrhea. Summary of the invention

[0031] In view of the deficiencies of the prior art, the present invention provides the use of Zengsun Zhenren Yangzang Decoction in the preparation of a drug for treating critical antibiotic-associated diarrhea. The Zengsun Zhenren Yangzang Decoction of the present invention can effectively treat critical antibiotic-associated diarrhea, alleviate the patient's clinical symptoms, and improve the patient's TCM syndrome, especially in reducing the number of bowel movements, improving stool characteristics, and improving the patient's overall condition. At the same time, Zengsun Zhenren Yangzang Decoction can effectively reduce the recurrence rate, has high safety, and has no obvious adverse reactions.

[0032] The active ingredients of the Zengsun Zhenren Yangzang Decoction of the present invention include the following ingredients in parts by weight: 13-17 parts of ginseng, 13-17 parts of angelica charcoal, 18-22 parts of stir-fried atractylodes, 13-17 parts of nutmeg, 5-7 parts of cinnamon, 8-12 parts of roasted licorice, 18-22 parts of stir-fried white peony root, 8-12 parts of stewed costusroot, 8-12 parts of stewed terminalia chebula, and 18-22 parts of pomegranate peel.

[0033] Preferably, the active ingredient raw materials of the Zengsun Zhenren Yangzang Decoction include the following raw materials in parts by weight: 15 parts of ginseng, 15 parts of angelica charcoal, 20 parts of stir-fried Atractylodes macrocephala, 15 parts of nutmeg, 6 parts of cinnamon, 10 parts of roasted licorice, 20 parts of stir-fried white peony root, 10 parts of stewed costusroot, 10 parts of stewed Terminalia chebula, and 20 parts of pomegranate peel.

[0034] Preferably, the application includes treating critical antibiotic-associated diarrhea characterized by spleen and kidney deficiency-cold syndrome.

[0035] Preferably, the medicine further comprises other Chinese herbal medicine extracts and / or other raw materials.

[0036] Preferably, the medicine is a tablet, chewable tablet, powder, granule, granule, capsule, paste, pill or liquid preparation.

[0037] The formula of the present invention is explained as follows:

[0038] According to the fact that the critical antibiotic-associated diarrhea is based on spleen and kidney yang deficiency, and the drug toxicity triggering the latent evil is the symptom of the disease. Therefore, this prescription uses a large dose of ginseng as the main medicine, mainly to nourish qi and nourish the internal organs. Angelica charcoal and stir-fried white atractylodes are the ministerial medicines. Angelica charcoal replenishes blood and activates blood circulation, and stir-fried white atractylodes strengthens the spleen and stomach. The two are used together to replenish qi and blood to correct the patient's deficiency. It is supplemented with nutmeg to warm the middle and astringe the intestines, and terminalia chebula to astringe the intestines and stop diarrhea. These two medicines embody the treatment principles of "treating the symptoms in an emergency" and "astringing the slippery". At the same time, cinnamon can warm the kidney and spleen, white peony can nourish blood and harmonize blood, and costus root is used to regulate qi and wake up the spleen. The combined use of these medicines jointly achieves the effect of regulating qi and blood. This can not only treat the symptoms of diarrhea, abdominal pain and heaviness, but also make the whole prescription not appear stagnant while astringing and nourishing. Licorice is used to invigorate the Qi and harmonize the middle, and to harmonize the various drugs. It can be used together with ginseng and Atractylodes macrocephala to invigorate the middle Qi, and can be used together with white peony root to relieve acute pain, playing a role as an adjuvant drug, making the whole prescription more harmonious and effective. On this basis, the applicant added pomegranate peel, which can strengthen the body, eliminate evil, astringe the intestines and detoxify.

[0039] Ginseng tastes sweet, slightly bitter, and slightly warm. It enters the spleen, lung, heart, and kidney meridians. The "Shennong's Herbal Classic" states: "It nourishes the five internal organs, calms the spirit, stabilizes the soul, stops panic, removes evil spirits, improves eyesight, and makes people happy and intelligent." Its main effects are to replenish vital energy, strengthen blood vessels, stabilize collapse, nourish the spleen and lungs, promote fluid production and replenish qi, and calm the mind. Ginseng occupies an important position in traditional Chinese medicine and is widely used to regulate the body and treat various diseases. This recipe takes its function of nourishing the five internal organs, spleen, and qi.

[0040] Angelica sinensis is sweet, pungent and warm, and enters the heart, liver, and spleen meridians. It is pungent, warm, fragrant and moist. The fragrance can enter the spleen, and the moisture can nourish the blood. The "Tangye Bencao" says: "Use the head to break the blood; use the tail to stop the bleeding; if the whole is used, one breaks and the other stops, which harmonizes the blood." It also records that it can penetrate into different meridians and exert different effects: entering the Taiyin spleen meridian of the foot can strengthen the spleen, entering the Shaoyin heart meridian of the hand can treat blood problems, and entering the Jueyin liver meridian of the foot can nourish the liver. This recipe takes its effect of nourishing blood and dispelling cold.

[0041] Atractylodes macrocephala is bitter, sweet and warm in nature, and enters the spleen and stomach meridians. The Compendium of Materia Medica states: "If the spleen is weak and unhealthy, Atractylodes macrocephala can replenish it; if the stomach is weak and unresponsive, Atractylodes macrocephala can help it." It has the functions of invigorating qi and strengthening the spleen, drying dampness and promoting diuresis. In addition, the Treatise on the Nature of Medicine records that Atractylodes macrocephala can treat cold pain in the abdomen, vomiting and diarrhea, and qi deficiency in the stomach. This recipe takes advantage of its effects of strengthening the spleen and stomach, drying dampness.

[0042] Nutmeg is pungent and warm, and it enters the spleen, stomach, and large intestine meridians. The "Compendium of Materia Medica" records that it "warms the middle, dispels adverse effects, and expels coldness." The "Illustrated Compendium of Materia Medica" calls it "cures spleen diarrhea and dysentery." This medicine can dissipate and eliminate, and has the functions of warming the middle, promoting qi, and astringing the intestines to stop diarrhea. It is pungent and warm, and can warm the spleen and stimulate the appetite, dispel yin and cold, and astringent can eliminate stale food, strengthen the large intestine, strengthen the spleen and intestines, thereby nourishing the middle earth to strengthen the acquired foundation. The prescription takes its effect of warming the middle and astringing the intestines.

[0043] Terminalia chebula is bitter, sour and astringent, and enters the lung and large intestine meridians. "Shenghui Fang" records that Terminalia chebula combined with alum can effectively treat the symptoms of chronic diarrhea in the elderly, and "Haiyao Bencao" records that it can treat "red and white dysentery". Sourness can astringe lung qi, clear away heat and reduce fire, and astringency can help astringe the intestines, stop diarrhea and consolidate. When used raw, its medicinal effect mainly acts on the lungs and can treat lung diseases; after being stewed and fried, its medicinal effect mainly acts on the intestines and has the effect of astringing and stopping diarrhea. This recipe takes its effect of astringing the intestines and stopping diarrhea.

[0044] Cinnamon bark is sweet, pungent, and hot. It enters the kidney, spleen, heart, and liver meridians. It has the effects of replenishing fire and yang, guiding fire back to the origin, dispersing cold and relieving pain, and warming and unblocking the meridians. "Compendium of Materia Medica" records that it can "warm the spleen and stomach and consolidate the large intestine". "Yuchu Yaojie" describes that the sweet and fragrant nature of cinnamon bark can replenish the spleen, and the pungent and sweet nature can relieve the liver. It is a good medicine for replenishing the spleen and regulating the liver. In addition, this medicine also has the effect of unblocking the meridians. It can restore yang and rescue adverse conditions by unblocking the heart meridian; it can warm the spleen meridian and warm the stomach; it can greatly replenish the original yang and nourish the kidney essence by unblocking the kidney meridian. The prescription takes its effects of warming the kidney and spleen, supporting yang and stopping diarrhea.

[0045] White peony root is bitter, sour, slightly cold, and enters the liver and spleen meridians. The New Compendium of Materia Medica records in detail the wonderful effects of white peony root in combination with other medicines. When white peony root is used together with angelica, it can significantly enhance the effect of treating dysentery; when used with licorice, it can quickly play an analgesic effect; and when used with cinnamon, it can make the effect of dispelling cold better. The Origin of Medicine discusses in detail the relationship between white peony root and spleen and stomach diseases, and clearly points out that white peony root can enter the spleen meridian, nourish the spleen, and absorb stomach qi and benefit the stomach. This prescription takes its effects of dispelling cold and relieving pain, nourishing blood and harmonizing blood.

[0046] Muxiang has a bitter, pungent and warm taste and enters the spleen, stomach, large intestine, triple burner and gallbladder meridians. It is warm in nature, pungent and bitter, and is good at regulating the qi of the large intestine. Its aromatic taste can also disperse the stagnant qi of the spleen and stomach. "Furen Daquan Liangfang" records that Muxiang has the effect of warming the spleen and stomach, stopping diarrhea and dysentery. "Rihuazi Bencao" also records that it has the effect of stopping diarrhea and dysentery. This recipe takes its effect of promoting qi and relieving pain, strengthening the spleen and digesting food.

[0047] Pomegranate peel is sour, astringent and warm, and belongs to the large intestine meridian. It has the effects of promoting fluid and quenching thirst, astringing and consolidating, and stopping bleeding. "Bielu" says that it can "cure diarrhea and stop spermatorrhea". It has significant antibacterial and astringent effects, and its astringent and antibacterial effects are used in the prescription.

[0048] Licorice root is sweet and mild, and it belongs to the heart, lung, spleen, and stomach meridians. It has the effects of tonifying the spleen and replenishing qi and alleviating the properties of the medicine. "Shennong's Herbal Classic" says that "taking it for a long time will make you light and prolong your life". It is an important medicine for regulating the middle and replenishing deficiency. It can be used with various spleen-strengthening and qi-tonifying medicines to enhance the effect of tonifying the middle and replenishing qi. In the recipe, it is used for its effect of replenishing qi and harmonizing the middle, so it is roasted.

[0049] The combination of various medicines takes both the symptoms and the root cause into consideration, and the whole prescription works together to invigorate Qi and activate blood circulation, warm the kidney and strengthen the spleen, astringe the intestines and stop diarrhea, and also has the function of harmonizing the stomach and detoxifying, so that the spleen and stomach can rise and fall, and the kidney's sealing and storing function is restored, then the evil Qi can be eliminated and diarrhea will stop.

[0050] Modern pharmacological effects of the single herb in the formula of the present invention:

[0051] The saponins in ginseng can not only upregulate IL-2, TNF-α, and IFN-γ, but also reduce immunosuppression and play an anti-shock role. In addition, it also has the function of regulating the digestion and absorption function of the human body, can effectively protect the gastrointestinal tract, and help relieve the symptoms of spleen deficiency. In addition, ginseng polysaccharides in the chemical composition of ginseng can activate and induce the proliferation of T and B lymphocytes, regulate the body's immune system, maintain its normal physiological functions, and not only promote specific immunity, but also enhance the effectiveness of nonspecific immunity.

[0052] The ethanol extract of Angelica sinensis can improve the symptoms of ulcerative colitis, significantly reduce the occurrence of diarrhea and occult blood, improve the symptoms of colon shortening and splenomegaly, protect colon tissue and reduce damage, anti-inflammatory, reduce serum immunoglobulin E levels, and regulate immunity; the compound Z-ligustilide isolated from Angelica sinensis can significantly alleviate the apoptosis caused by oxidative stress in endothelial cells. In addition, the coumarin components of Angelica sinensis have significant effects. For example, osthole and its derivatives have an inhibitory effect on Staphylococcus aureus, and umbelliferone significantly inhibits the growth of Pseudomonas aeruginosa, and can significantly reduce the motility of Pseudomonas aeruginosa colonies, the amount of virulence factor production, and the expression of genes related to quorum sensing.

[0053] Atractylodes macrocephala extract and its core chemical component, atractylodes lactone I, exhibit multiple pharmacological effects, including regulating gastrointestinal function, inhibiting inflammatory responses, and enhancing the immune system. Atractylodes lactone III can inhibit the expression of matrix metalloproteinases, thereby reducing damage to the extracellular matrix and effectively preventing the formation of gastric ulcers. Atractylodes polysaccharides can promote the migration of these cells and the expression of E-cadherin by increasing the calcium ion concentration in ICE-6 cells, thereby contributing to the repair process of gastrointestinal mucosal damage. Other studies have shown that Atractylodes macrocephala has a regulatory effect on intestinal microorganisms, can significantly correct the imbalance of intestinal flora, and regulate the composition and activity of intestinal microbial communities.

[0054] The volatile oil and phenylpropanoid compounds in nutmeg play a protective role on the intestine by affecting the activity of neurotransmitters, inflammatory factors and antioxidant enzymes. Among them, the water extract of nutmeg can block the effects of acetylcholine receptors and histamine receptors, thereby helping to alleviate the symptoms of intestinal spasm. The volatile oil of nutmeg helps to reduce the level of inflammation by reducing the expression of IL-8 and NF-κBp65 proteins in intestinal tissue, thereby promoting the repair of intestinal mucosal damage. In addition, nutmeg can also improve gastric damage by increasing the level of hormones related to vascular repair and enhancing antioxidant effects. The results of the study showed that the crude oil suspension of nutmeg can enhance the tension of the guinea pig intestine, while its petroleum ether extract can inhibit the contraction activity of the ileum. These two effects work together to exert the antidiarrheal effect of nutmeg.

[0055] Studies have shown that Terminalia chebula extract can improve intestinal edema and bleeding, intestinal villus damage, protect intestinal mucosa and relieve diarrhea symptoms.

[0056] Cinnamon contains a variety of ingredients with antibacterial effects, including cinnamon oil, cinnamic acid and cinnamaldehyde extracted from it. Studies have shown that the ethanol extract in cinnamon has a significant inhibitory effect on the growth of bacteria in meat products. In addition, the combination of cinnamon and aconite can restore the rhythm of normal intestinal movement. Studies have shown that when aconite and cinnamon are used in a ratio of 2:1, the combination can increase the expression levels of SCF, c-Kit genes and proteins, upregulate colon 5-HT and SP, and downregulate VIP expression, and has a positive regulatory effect on intestinal dysfunction in yang deficiency type STC rats. The formula of the present invention mainly utilizes the antibacterial effect of cinnamon.

[0057] The main component of white peony root is paeoniflorin, and studies have shown that it can regulate cell membrane Ca 2+ / Na + The exchange relaxes smooth muscle cells, inhibits the excitement of the parasympathetic nerves, reduces the tension of the smooth muscles, and thus inhibits the movement of the smooth muscles to achieve the purpose of relieving spasms. In addition, paeoniflorin can relax the sphincter, promote the secretion of bile and pancreatic juice, and reduce the damage to the pancreatic acinus caused by the activation of pancreatic enzymes.

[0058] Costus root has many pharmacological effects, which can promote gastrointestinal motility, effectively stop diarrhea, protect the integrity of gastric mucosa, resist the formation of ulcers, and help the secretion and excretion of bile. Costus root decoction and volatile oil promote gastric emptying and intestinal propulsion; Costus root extract can effectively inhibit the spasm of gastrointestinal smooth muscle and relieve acute gastric mucosal damage. In addition, costus root and white atractylodes can also optimize intestinal motility and sensitivity and relieve diarrhea by improving the changes in intestinal flora structure, reducing 5-HT expression, and increasing 5-HT4R and SERT expression extracts.

[0059] The extract of pomegranate peel has a significant anti-inflammatory effect. It can reduce the production of inflammatory factors such as IL-1β, IL-6, TNF-α, and IFN-γ, and increase the expression of anti-inflammatory factors. In addition, the extract can also reduce the degree of oxidative stress and the level of the inflammatory marker MPO, thereby helping to repair the damage to the colon epithelial structure caused by the inflammatory response and protect the intestinal mucosa. Studies have shown that ellagic acid in pomegranate peel has a better gastrointestinal protective effect than punicalagin and punicalagin. It has superior ability to repair intestinal damage and resist diarrhea. Not only that, pomegranate peel also shows strong resistance to drug-resistant bacteria, and can significantly inhibit the growth and reproduction of Helicobacter pylori, metronidazole-resistant strains and sensitive strains.

[0060] Licorice has analgesic, anti-inflammatory, immune-enhancing and antioxidant effects. The licorice flavonoids contained in licorice have the ability to regulate the level of prostaglandin E2 (PGE2), thereby achieving its significant effect of inhibiting inflammation. Other studies have revealed that when peony and licorice are used together, they can significantly exert a synergistic analgesic effect and effectively relieve pain.

[0061] The present invention adjusts the combination of monarch, minister, assistant and envoy of Zhenren Yangzang Decoction, takes ginseng as the monarch medicine, highlights the core role of regulating and nourishing the five internal organs, provides the application of Zengsun Zhenren Yangzang Decoction for preparing a drug for treating critical antibiotic-associated diarrhea, and follows the treatment principle of "invigorating qi and activating blood circulation, warming the kidney and strengthening the spleen, astringing the intestines and stopping diarrhea, and harmonizing the stomach and detoxifying".

[0062] The Zengsun Zhenren Yangzang Decoction of the present invention has shown good efficacy in the treatment of antibiotic-associated diarrhea in critically ill patients. It can not only effectively alleviate the diarrhea symptoms of patients and improve related TCM syndromes, but also alleviate other accompanying clinical manifestations, such as abdominal pain, hyperactive bowel sounds, etc., reducing the burden of clinical nursing.

[0063] Zengsun Zhenren Yangzang Decoction also showed good efficacy in improving patients' gastrointestinal function and overall health status. Critically ill patients are in serious condition and have poor gastrointestinal function. Zengsun Zhenren Yangzang Decoction provides comprehensive care for patients based on the holistic view of traditional Chinese medicine and syndrome differentiation and treatment, with obvious clinical effects.

[0064] The recurrence rate of Zengsun Zhenren Yangzang Decoction in the treatment of critical antibiotic-associated diarrhea is relatively low, and no obvious adverse reactions were found, with good safety. BRIEF DESCRIPTION OF THE DRAWINGS

[0065] Figure 1 Completion status of patients in the two groups (n).

[0066] Figure 2 Gender comparison between the two groups of patients (n).

[0067] Figure 3 Comparison of age between the two groups of patients (years).

[0068] Figure 4 Comparison of antibiotic use between the two groups of patients (n).

[0069] Figure 5 Comparison of feeding methods between the two groups of patients (n).

[0070] Figure 6 Comparison of underlying diseases between the two groups of patients (n).

[0071] Figure 7 Comparison of C-reactive protein (mg / L) between the two groups of patients.

[0072] Figure 8 Comparison of lactate levels between the two groups of patients (mmol / L).

[0073] Fig. 9 Comparison of white blood cell counts between the two groups (×10 9 / L).

[0074] Fig.10 For other general comparisons.

[0075] Fig.11 Comparison of the overall efficacy of AAD between the two groups of patients (n).

[0076] Fig.12 To compare the total scores of AAD symptoms between the two groups of patients before and after treatment.

[0077] Fig.13 Comparison of AAD symptom scores between the two groups of patients before and after treatment.

[0078] Fig.14A This is a comparison of the AAD symptom scores between the two groups before treatment.

[0079] Fig. 14B This is a comparison of the AAD symptom scores between the two groups after treatment.

[0080] Fig. 14C Comparison of AAD symptom scores before and after treatment in the experimental group.

[0081] Fig.14D Comparison of AAD symptom scores before and after treatment in the control group.

[0082] Fig.15 To compare the gastrointestinal dysfunction scores between the two groups before and after treatment.

[0083] Fig.16 To compare the gastrointestinal dysfunction scores between the two groups of patients before and after treatment.

[0084] Fig.17 Comparison of APACHE II scores between the two groups before and after treatment.

[0085] Fig.18 APACHE II scores were compared between the two groups before and after treatment.

[0086] Fig.19 Comparison of the overall efficacy of TCM syndromes between the two groups of patients (n).

[0087] Fig. 20 To compare the total scores of TCM syndromes between the two groups of patients before and after treatment.

[0088] Fig.21 To compare the total scores of TCM syndromes between the two groups of patients before and after treatment.

[0089] Fig.22A This is a comparison of the TCM syndrome scores of the two groups before treatment.

[0090] Fig. 22B To compare the TCM syndrome scores between the two groups after treatment.

[0091] Fig. 22CThis is a comparison of the scores of various TCM syndromes in the experimental group before and after treatment.

[0092] Fig.22D Comparison of TCM syndrome scores in the control group before and after treatment.

[0093] Fig.23 Comparison of recurrence rates between the two groups (n). DETAILED DESCRIPTION

[0094] The following is a clear and complete description of the technical solutions in the embodiments of the present invention in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0095] Example 1

[0096] Zengsun Zhenren Yangzang Decoction: 15g ginseng, 15g angelica charcoal, 20g stir-fried Atractylodes macrocephala, 15g nutmeg, 6g cinnamon, 10g roasted licorice, 20g stir-fried white peony root, 10g stewed costusroot, 10g stewed Terminalia chebula, 20g pomegranate peel.

[0097] After the medicine is decocted, divide it into two bags, each with a capacity of 100 ml. Soak and heat the medicine in warm water before taking it to make the medicine reach an appropriate temperature, about 40°C is preferred, and use a 50ml sterile syringe to draw it out. Take it orally or through nasogastric feeding 1 hour after normal nasogastric feeding in the morning and evening. Continue treatment for 1 week.

[0098] Research on the beneficial effects of the present invention:

[0099] 1. Research Data and Methods

[0100] 1. Research Materials

[0101] 1. Research subjects

[0102] The clinical observation subjects of this study were all from the emergency and critical care medicine ward of Zhejiang Provincial Tongde Hospital. The case collection time was from August 2022 to February 2024, and all patients met the diagnostic criteria for critical antibiotic-associated diarrhea.

[0103] 2. Diagnostic criteria and syndrome differentiation criteria

[0104] 2.1 Western medicine diagnostic criteria

[0105] Refer to "2003 Hospital Infection Diagnostic Criteria (Trial)".

[0106] For patients who have diarrhea symptoms after recent or current use of antibiotics, changes in stool properties may be observed, such as watery stools, blood in the stool, mucus or pus and blood, and even plaque-like pseudomembranes. It may be accompanied by one of the following conditions: ① fever symptoms with a body temperature of 38°C or above; ② abdominal pain or abdominal tenderness, rebound pain and other signs; ③ increased peripheral white blood cell count. In addition, when making an etiological diagnosis, it must be based on the premise of meeting the clinical diagnosis. If any of the following three conditions is met, the diagnosis can be confirmed: ① stool smear shows an imbalance of flora, or the culture results show a significant dominant flora; ② if conditions permit, during a fiber colonoscopy, symptoms such as congestion, edema and bleeding in the intestinal wall are observed, or a gray-yellow (white) plaque-like pseudomembrane with a diameter of 2 to 20 mm is found; ③ the bacterial toxin test result is positive. It should be noted that: ① The definition of acute diarrhea refers to diarrhea occurring 3 times or more within 24 hours; ② Diarrhea caused by acute attacks of chronic enteritis, acute gastrointestinal infections and non-infectious factors needs to be excluded.

[0107] 2.2 Diagnostic criteria for diarrhea in traditional Chinese medicine

[0108] Based on the 2002 edition of the "Guidelines for Clinical Research of New Chinese Medicines (Trial)" and the "Expert Consensus on Diagnosis and Treatment of Diarrhea in Traditional Chinese Medicine (2017)", combined with clinical:

[0109] ① The number of bowel movements is greater than 3 times per day, and the stool is very loose and watery or contains undigested food;

[0110] ②Abdominal distension with sound, possibly accompanied by vomiting;

[0111] ③Fever, fatigue, dry skin, etc.;

[0112] ④Symptoms persist for >24 hours.

[0113] The above items are essential, and the rest are concomitant symptoms.

[0114] 2.3 Syndrome differentiation criteria for spleen and kidney deficiency and coldness:

[0115] Main symptoms: unformed stools, loose stools or even watery stools, or undigested food.

[0116] Secondary symptoms: ① loss of appetite; ② fatigue; ③ tiredness and laziness; ④ cold pain in the navel and abdomen; ⑤ chills and cold limbs; ⑥ soreness and coldness in the waist and knees.

[0117] Tongue and pulse: ① Pale tongue with thin white fur; ② Deep and thin or weak pulse.

[0118] Diagnosis of syndrome type: The main symptoms are necessary symptoms, and diagnosis can be made if 1 to 2 secondary symptoms are met. Tongue and pulse can be used as reference.

[0119] 3. Inclusion criteria

[0120] ①Age ≥ 18 years old, regardless of gender;

[0121] ②Meet the diagnostic criteria for antibiotic-associated diarrhea;

[0122] ③ The patient has two or more organ system functions that are unstable, reduced or failing, and the acute physiology and chronic health evaluation score (APACHE II score) is greater than 15 points;

[0123] ④Meet the syndrome differentiation criteria of spleen and kidney deficiency and coldness;

[0124] ⑤ No obvious contraindications to the use of research medications;

[0125] ⑥Agree to participate in this study and sign the informed consent form, and can take medication according to the doctor's advice.

[0126] 4. Exclusion criteria

[0127] ① Patients with diarrhea caused by other reasons;

[0128] ②Pregnant or lactating women;

[0129] ③ Those who are allergic to the drugs used in the program;

[0130] ④ Patients with severe liver and kidney diseases, hematopoietic system diseases, endocrine system diseases, etc. that may cause diarrhea, as well as patients with mental illness;

[0131] ⑤ The patient has developed serious complications such as coma, shock, gastrointestinal bleeding, etc. upon admission, and the doctor has assessed the patient's condition and determined that the patient may be in danger of death within the next 24 hours;

[0132] ⑥ Currently, patients who have participated in other clinical trials.

[0133] If any of the above conditions are met, the relevant cases will be excluded.

[0134] 5. Rejection and shedding criteria

[0135] ① Those who did not meet the inclusion criteria and were mistakenly included, failed to cooperate in completing the trial, violated the drug use regulations and clinical trial protocols, and accepted other drug experiments during the trial, etc., will be excluded.

[0136] ② If statistical analysis cannot be performed due to incomplete data, or if serious adverse reactions or special physiological changes occur and the patient is no longer suitable to continue participating in the trial, or if the patient is lost to follow-up or voluntarily withdraws, these cases will be regarded as dropouts.

[0137] 6. Suspension criteria

[0138] ①Serious adverse events related to study drugs occur;

[0139] ② After evaluation, the researcher believes that continuing the trial may cause potential harm to the subjects;

[0140] ③The subject requests to terminate the treatment trial early due to various factors.

[0141] 7. Ethical requirements

[0142] This study has been approved by the relevant ethics review department (Zhejiang Tongde Ethics Review No.

[2022] 178), and all subjects have been informed of the relevant risks and signed informed consent.

[0143] 2. Research Methods

[0144] 1. Sample size estimation

[0145] This study is a clinical study, and the design strictly follows the principle of randomized control. The outcome indicators of this study are the final treatment efficacy of the experimental group and the control group, and the calculation of the sample size is based on the following formula:

[0146]

[0147] According to previous literature on the comparative diagnosis and treatment of critical antibiotic-associated diarrhea with Chinese and Western medicine, P1 is the Chinese medicine treatment group with an effective rate of about 90%, and P2 is the Western medicine control group with an effective rate of about 50%. According to the statistical sample size principle, α = 0.05, β = 0.1, then Z α =1.96, Z β =1.28, represents the mean of P1 and P2, Representing the mean of 1-P1 and 1-P2, according to the sample size estimation formula, based on the requirements of the "Guidelines for Clinical Research of New Chinese Medicines", and the previous visits of the subjects in the emergency medicine ward of our hospital, plus the expected maximum dropout rate of 10%, it can be calculated that n1=n2≈30 cases, so at least 60 subjects need to be included.

[0148] 2. Grouping method

[0149] The 60 subjects collected in this study were randomly divided into groups using a random number table generated by statistical software SPSS27.0, and finally 30 subjects in each control group and experimental group were obtained.

[0150] 3. Treatment options

[0151] 3.1 Basic treatment:

[0152] Routine care, reasonable selection of enteral nutrition preparations, active control of infection, maintenance of respiratory circulation and internal environment stability, active optimization of microcirculation, maintenance of water, electrolyte and acid-base balance, maintenance of normal vital signs and routine treatment of other underlying diseases.

[0153] 3.2 Experimental group (TCM treatment group)

[0154] The patient was treated with Zengsun Zhenren Yangzang Decoction (15g of ginseng, 15g of angelica charcoal, 20g of stir-fried Atractylodes macrocephala, 15g of nutmeg, 6g of cinnamon, 10g of roasted liquorice, 20g of stir-fried white peony root, 10g of stewed costusroot, 10g of stewed terminalia chebula, and 20g of pomegranate peel), which was decocted by the preparation room of Zhejiang Provincial Tongde Hospital (Zhejiang Medicine Preparation No. Z20200025000). After each dose of medicine was decocted, it was divided into two bags, each with a capacity of 100ml. Before taking the medicine, it was soaked and heated in warm water to make the medicine reach an appropriate temperature, preferably about 40℃, and drawn with a 50ml sterile syringe. It was taken orally or nasogastrically one hour after normal nasogastric feeding in the morning and evening. The treatment was continued for 1 week.

[0155] 3.3 Control group

[0156] The patient was given montmorillonite powder (3 grams per bag, produced by Zhejiang Hailisheng Pharmaceutical Co., Ltd.). The first dose was doubled, that is, 2 bags were taken for the first time, and 1 bag was taken each time thereafter. After the montmorillonite powder was dissolved in cold water, it was given to the patient through nasogastric feeding, 3 times a day. At the same time, 3 capsules of Bifidobacterium Triple Live Bacteria Capsules (210 mg per capsule, produced by Shanghai Xinyi Pharmaceutical Co., Ltd., National Medicine Standard No. S10950032) were taken each time, dissolved in warm water, and given through nasogastric feeding, 3 times a day. The above treatment plan will continue for 1 week.

[0157] 4. Observation indicators

[0158] 4.1 General

[0159] At enrollment, the subjects' gender, age, antibiotic use, feeding method, underlying disease composition, CRP, lactic acid, white blood cell count, mean arterial pressure, oxygenation index, body temperature, respiration, heart rate and other baseline conditions were recorded, and statistical analysis was performed to determine whether they affected the test results.

[0160] 4.2 AAD efficacy indicators

[0161] Antibiotic-associated diarrhea symptom score: Referring to the standards of the "Guidelines for Clinical Research of New Chinese Medicines (Trial)" promulgated in 2002, the severity of symptoms in the two groups before and after treatment was observed, and the symptom score = ∑ (symptom severity) was calculated.

[0162] 4.3 Critical illness related indicators

[0163] ① Gastrointestinal dysfunction score: It is based on the GIF scoring system proposed by Reintam in 2008. An assessment will be conducted before treatment and on the 7th day after treatment. The higher the score, the worse the gastrointestinal function.

[0164] ②APACHE II score: It covers the following three aspects of assessment: first, the assessment of acute physiological parameters, second, the consideration of chronic health conditions, and finally, the age score. The scores of these three parts will be added up to get the final score. Such a comprehensive assessment will be conducted before treatment and on the 7th day after treatment. The higher the score, the worse the patient's basic condition.

[0165] 4.4 TCM Syndrome Efficacy Indicators

[0166] The TCM syndrome scale was developed with reference to the 2002 edition of the "Guidelines for Clinical Research of New Chinese Medicines (Trial)". This scale is based on the severity of the symptoms and uses a four-level grading standard to score each symptom (level 0 means that the patient has no relevant symptoms; level I means that the symptoms are relatively mild and have almost no impact on daily life; level II means that the symptoms become more obvious and have a certain degree of impact on daily life; level III means that the symptoms are serious and have caused significant adverse effects on the patient's work and life). They are recorded as 0, 1, 2, and 3 points respectively. The TCM syndrome score is the sum obtained by adding up the scores of each symptom.

[0167] 4.5 Relapse assessment

[0168] In the first week after the effective treatment, the subjects completed the treatment course and were followed up to evaluate the recurrence. During the follow-up, the antibiotic-associated diarrhea symptom score of the subjects was compared with the data at the end of treatment to determine the recurrence rate.

[0169] 4.6 Safety Observation

[0170] The vital signs of the two groups of subjects were recorded, including blood pressure, respiration, heart rate and body temperature. At the same time, the relevant test results of the two groups of subjects were recorded, mainly covering three routine items, liver and kidney function indicators, inflammation-related indicators and electrolyte tests. In addition, the routine electrocardiogram results of the two groups of subjects will also be recorded. During the study, if any adverse reactions occur in the subjects, they will be recorded immediately and corresponding measures will be taken, and the correlation between these adverse reactions and the test drugs will be analyzed.

[0171] 5. Evaluation Criteria

[0172] 5.1 AAD Western medicine efficacy evaluation criteria

[0173] Effective rate = (clinical cure + marked effect + number of effective cases) ÷ total number of cases × 100%.

[0174] ①Clinical cure: Diarrhea disappears within 1 week after treatment, and stool characteristics return to normal;

[0175] ② Significantly effective: within one week after treatment, the diarrhea score is reduced by 6 points and the stool shape returns to normal;

[0176] ③ Effective: 3 points ≤ The diarrhea severity score decreased by <6 points within 1 week after treatment;

[0177] ④ Ineffective: The diarrhea severity score decreases by less than 3 points within 1 week after treatment, or there is no obvious change in stool shape.

[0178] 5.2 Evaluation criteria for TCM syndrome efficacy of AAD

[0179] The nimodipine method was used for calculation. The specific efficacy index was obtained by the following formula:

[0180] Efficacy index = (score before treatment - score after treatment) ÷ score before treatment × 100%. Based on this index, we can divide the efficacy into the following four levels:

[0181] ① Clinical recovery: when the main symptoms and signs completely disappear or almost disappear, and the efficacy index is ≥95%;

[0182] ② Significantly effective: if the main symptoms and signs are significantly improved, and the efficacy index is 70% ≤ < 95%;

[0183] ③ Effective: When the main symptoms and signs improve, and the efficacy index is 30% ≤ < 70%;

[0184] ④ Ineffective: If the main symptoms and signs are not significantly improved, or even worsen, and the efficacy index is less than 30%.

[0185] Total effective rate = (number of cured cases + number of markedly effective cases + number of effective cases) ÷ total number of cases × 100%.

[0186] 5.3 Recurrence rate evaluation criteria

[0187] (Total AAD score before treatment - Total AAD score during follow-up) ÷ Total AAD score before treatment × 100% ≤ 30% is considered as recurrence;

[0188] If the total AAD score during follow-up is ≥ the total AAD score before treatment, it is also considered as recurrence.

[0189] Recurrence index = (total AAD score at follow-up - total AAD score after treatment) ÷ total AAD score at follow-up × 100%,

[0190] Recurrence rate = number of recurrence cases ÷ number of follow-up cases × 100%.

[0191] 5.4 Safety evaluation criteria

[0192] Formulated with reference to the 2002 edition of the "Guidelines for Clinical Research of New Chinese Medicines (Trial)":

[0193] ① Grade I: safe, no adverse reactions were observed during treatment;

[0194] ② Grade II: relatively safe. Even if adverse reactions occur, no special treatment is required and subsequent medication can be continued;

[0195] ③Level III: There are safety issues and some adverse reactions may occur during the trial, but the trial can continue after appropriate treatment;

[0196] ④Grade IV: If serious adverse reactions occur, the clinical trial must be terminated immediately.

[0197] 3. Statistical methods

[0198] SPSS27.0 software was used to analyze the data in this study. For measurement data that conformed to normal distribution, t-test was used; for count data, Fisher's exact test was used. For measurement data and rank data that were not normally distributed, Mann-Whitney U nonparametric rank sum test was used for analysis. Analysis results: Measurement data were expressed as mean (χ) ± standard deviation (s) or quartiles, while rank data were presented in the form of number of cases and percentage (%), so as to more intuitively show the distribution and characteristics of the data. In terms of statistical significance, α = 0.05 was set. If P < 0.05, the test results were significantly different; if P > 0.05, the test results were not statistically different.

[0199] 2. Results

[0200] 1. Case completion status

[0201] This study enrolled a total of 62 patients from August 2022 to February 2024, and randomly divided the patients into an experimental group and a control group, with 31 patients in each group. Among them, one patient in both the control group and the experimental group was excluded from the study because he was unable to cooperate in completing the scale. After strict screening, 30 patients in the experimental group and the control group finally completed the entire study process. Overall, the dropout rate of this study was 3.30%. See Table 1 for details. Figure 1 :

[0202] Table 1 Completion status of patients in the two groups (n)

[0203]

[0204] (II) Comparison of general data

[0205] 1. Gender comparison

[0206] This study successfully recruited a total of 60 subjects, including 28 males and 32 females. Further subdivided, there were 13 males and 17 females in the experimental group, with a male-to-female ratio of approximately 1:1.31; while there were 15 males and 15 females in the control group, with a male-to-female ratio of 1:1. Statistical analysis showed no significant difference in gender distribution between the experimental group and the control group (P>0.05), so the two groups were comparable in terms of gender composition. See Table 2 for details. Figure 2 .

[0207] Table 2 Comparison of gender between the two groups of patients (n)

[0208]

[0209] Note: The gender of the two groups was compared using Fisher's exact test.

[0210] 2. Age comparison

[0211] Among the 60 subjects whose data were completely collected, the oldest was 85 years old and the youngest was 40 years old. The age distribution of the experimental group was between 41 and 85 years old, with a median age of 78 years old; the age distribution of the control group was between 40 and 85 years old, with a median age of 76.5 years old. The age of the patients in the experimental and control groups was non-normally distributed, and the ages of the two groups of subjects could be analyzed using a non-parametric rank sum test. The results showed that there was no statistical difference in age between the two groups (P>0.05), and they were comparable. See Table 3 for details. Figure 3 :

[0212] Table 3 Comparison of age between the two groups of patients (years)

[0213]

[0214] 3. Comparison of antibiotic use

[0215] Among the 60 subjects finally included, the main way of using antibiotics was triple therapy. Specifically, there were 11 cases of single-drug use, 14 cases of dual-drug use, and 35 cases of triple-drug use. In the experimental group, there were 6 subjects using single-drug use, 7 subjects using dual-drug use, and 17 subjects using triple-drug use. In the control group, there were 5 cases of single-drug use, 7 cases of dual-drug use, and 18 cases of triple-drug use. There was no statistical difference in the use of antibiotics between the experimental and control groups (P>0.05), and the two groups were comparable. See Table 4 for details. Figure 4 .

[0216] Table 4 Comparison of antibiotic use between the two groups of patients (n)

[0217]

[0218] Note: The gender of the two groups was compared using Fisher's exact test.

[0219] 4. Comparison of feeding methods

[0220] A total of 60 subjects were finally included, and their feeding methods were mainly divided into two types: enteral nutrition and parenteral nutrition. Among them, 21 subjects in the experimental group used enteral nutrition, and 9 subjects in parenteral nutrition. A total of 24 subjects in the control group used enteral nutrition, and 6 subjects in parenteral nutrition. There was no statistical difference in feeding methods between the experimental group and the control group (P>0.05), and they were comparable. See Table 5 for details. Figure 5 .

[0221] Table 5 Comparison of feeding methods between the two groups of patients (n)

[0222]

[0223] Note: The gender of the two groups was compared using Fisher's exact test.

[0224] 5. Comparison of underlying disease composition

[0225] Comparison of the underlying diseases of the 60 subjects finally included found that in the experimental group, there were 24 cases of essential hypertension, 16 cases of type 2 diabetes, 17 cases of coronary atherosclerotic heart disease, 15 cases of cerebrovascular disease, and 22 cases of sepsis. In the control group, there were 20 cases of essential hypertension, 21 cases of type 2 diabetes, 14 cases of coronary atherosclerotic heart disease, 10 cases of cerebrovascular disease, and 20 cases of sepsis. There was no statistical difference in the composition of underlying diseases between the experimental group and the control group (P>0.05), and they were comparable. See Table 6 for details. Figure 6 .

[0226] Table 6 Comparison of underlying diseases between the two groups of patients (n)

[0227]

[0228] Note: The gender of the two groups was compared using Fisher's exact test.

[0229] 6. Comparison of C-reactive protein

[0230] The C-reactive protein of the 60 subjects finally included was statistically analyzed, and it was found that the C-reactive protein values ​​of the patients in the experimental group and the control group were non-normally distributed, and the non-parametric rank sum test could be used for analysis. The results showed that there was no statistical difference in age between the two groups (P>0.05), and they were comparable. See Table 7 for details. Figure 7 :

[0231] Table 7 Comparison of C-reactive protein between the two groups of patients (mg / L)

[0232]

[0233] 7. Lactic acid comparison

[0234] The lactic acid status of the 60 subjects finally included was statistically analyzed, and it was found that the lactic acid values ​​of the experimental group and the control group were non-normally distributed, and the non-parametric rank sum test could be used for analysis. The results showed that there was no statistical difference in age between the two groups (P>0.05), and they were comparable. See Table 8 for details. Figure 8 :

[0235] Table 8 Comparison of lactic acid between the two groups of patients (mmol / L)

[0236]

[0237] 8. Comparison of white blood cell count

[0238] The white blood cell counts of the 60 subjects included in the final study were statistically analyzed, and it was found that the white blood cell counts of the patients in the experimental group and the control group were non-normally distributed, and the non-parametric rank sum test could be used for analysis. The results showed that there was no statistical difference in age between the two groups (P>0.05), and they were comparable. See Table 9 for details. Fig. 9 :

[0239] Table 9 Comparison of white blood cell counts between the two groups of patients (×10 9 / L)

[0240]

[0241] 9. Other general comparisons

[0242] The other general conditions of the 60 subjects finally included were statistically analyzed. It was found that the heart rate, body temperature, respiration, oxygenation index, and mean arterial pressure of the experimental group and the control group were all non-normally distributed, and non-parametric rank sum test analysis was used. The results showed that there was no statistical difference in other general conditions between the two groups (P>0.05), and they were comparable. See Table 10 for details. Fig.10 :

[0243] Table 10 Comparison of other general conditions

[0244]

[0245]

[0246] 3. Comparison of efficacy

[0247] 1. Comparison of overall efficacy

[0248] The total efficacy of AAD in Western medicine for the 60 subjects finally included was statistically analyzed. It was found that after one week of treatment, the total effective rate of AAD in the experimental group was 83.30%, and that in the control group was 60.00%. The total effective rate between the two groups was statistically significant (P < 0.05). See Table 11 for details. Fig.11 :

[0249] Table 11 Comparison of AAD efficacy between the two groups of patients (n)

[0250]

[0251] Note: The overall efficacy of AAD between the two groups was compared using Fisher's exact test.

[0252] 2. Comparison of AAD symptom scores

[0253] 2.1 Comparison of total AAD symptom scores between the two groups before and after treatment

[0254] The total scores of Western medicine symptoms of the 60 subjects finally included were statistically analyzed, and it was found that the total scores of AAD symptoms of the two groups of patients before treatment and the difference before and after treatment were non-normally distributed. Non-parametric rank sum test analysis can be used. The results show that there was no statistical difference in the total scores of AAD symptoms of the two groups of patients before treatment (P>0.05). After 1 week of treatment with different regimens, the difference in the total scores of AAD symptoms of the two groups of patients before and after was different (P<0.01). See Table 12 for details. Fig.12 :

[0255] Table 12 Comparison of total AAD symptom scores between the two groups before and after treatment

[0256]

[0257] 2.2 Comparison of total AAD symptom scores between the two groups before and after treatment

[0258] A statistical analysis was performed on the total scores of Western medicine symptoms of the 60 subjects finally included. The results showed that before and after treatment, the total scores of AAD symptoms in the two groups of patients showed a non-normal distribution. Non-parametric rank sum test analysis was used. The results suggested that the total scores of AAD symptoms in both the experimental group and the control group after treatment were significantly different from those before treatment (P < 0.01).

[0259] See Table 13 for details. Fig.13 :

[0260] Table 13 Comparison of AAD symptom scores between the two groups before and after treatment

[0261]

[0262] 2.3 Comparison of AAD symptom scores

[0263] After one week of treatment with different regimens, the AAD symptom scores of the experimental group and the control group showed statistical differences compared with those before treatment (P < 0.05): the symptom scores in the experimental group showed significant statistical differences (P < 0.01), the dehydration in the control group showed statistical differences compared with those before treatment (P < 0.05), and the other symptom scores showed significant statistical differences compared with those before treatment (P < 0.01). Before treatment, we conducted a statistical analysis on the symptom scores of the two groups and found no statistical difference (P > 0.05), which showed comparability. After treatment, by comparing the symptom scores of the two groups, we found that there were significant statistical differences in the number of diarrhea, stool characteristics, abdominal pain, and bowel sounds (P < 0.05), while there was no statistical difference in dehydration (P > 0.05). See Table 14 and Figure 14 for details. (The comparison of the AAD symptom scores was performed using the non-parametric rank sum test)

[0264] Table 14 Comparison of AAD symptom scores between the two groups of patients before and after treatment

[0265]

[0266] 3. Comparison of gastrointestinal dysfunction scores

[0267] 3.1 Comparison of gastrointestinal dysfunction scores between the two groups before and after treatment

[0268] The gastrointestinal dysfunction scores of the 60 subjects finally included before and after treatment were statistically analyzed, and the results showed that these scores did not conform to the normal distribution. Therefore, we used the non-parametric rank sum test for data analysis. The analysis results showed that before treatment, there was no statistical difference in the gastrointestinal dysfunction scores of the two groups of patients (P>0.05), and they were comparable. After one week of different treatment regimens, there was a statistical difference in the gastrointestinal dysfunction scores of the two groups of patients (P<0.05). See Table 15 for details. Fig.15 .

[0269] Table 15 Comparison of gastrointestinal dysfunction scores between the two groups of patients before and after treatment

[0270]

[0271] 3.2 Comparison of gastrointestinal dysfunction scores between the two groups before and after treatment

[0272] The gastrointestinal dysfunction scores of the two groups of patients before and after treatment were non-normally distributed, and non-parametric rank sum test analysis was used. The results showed that the gastrointestinal dysfunction scores of the experimental group after treatment were significantly different from those before treatment (P < 0.01), and there was no statistical difference in the gastrointestinal dysfunction scores of the control group after treatment compared with those before treatment (P > 0.05). See Table 16 for details. Fig.16 .

[0273] Table 16 Comparison of gastrointestinal dysfunction scores between the two groups of patients before and after treatment

[0274]

[0275] 4. Comparison of APACHE II scores

[0276] 4.1 Comparison of APACHE II scores between the two groups before and after treatment

[0277] The APACHE II scores of the 60 subjects finally included were statistically analyzed, and it was found that the APACHE II scores of the two groups of patients before and after treatment were in line with the normal distribution, which could be analyzed using the t-test. The results showed that the mean score of the experimental group before treatment was 23.93±2.50, and the mean score of the control group was 24.20±2.19. The results showed no statistical difference (P>0.05), and they were comparable. After 1 week of treatment with different regimens, the mean score of the experimental group was 20.83±3.49, and the mean score of the control group was 22.77±2.27. The results showed that the difference in the scores was statistically significant (P<0.05). See Table 17 for details. Fig.17 .

[0278] Table 17 Comparison of APACHE II scores between the two groups before and after treatment

[0279]

[0280] 4.2 Comparison of APACHE II scores between the two groups before and after treatment

[0281] The APACHE II scores of the two groups of patients before and after treatment were in accordance with normal distribution, and the t-test analysis was used. The results showed that after one week of treatment with different regimens, the APACHE II scores of the two groups of patients were significantly different from those before treatment (P < 0.01). See Table 18 for details. Fig.18 .

[0282] Table 18 Comparison of APACHE II scores between the two groups before and after treatment

[0283]

[0284] 5. Comparison of TCM Syndrome Therapy

[0285] 5.1 Comparison of overall efficacy of TCM syndromes

[0286] After one week of treatment with Zengsun Zhenren Yangzang Decoction or Western medicine alone, the total effective rate of TCM syndrome in the experimental group was 86.70%, and that in the control group was 50.00%. The total effective rate between the two groups was statistically significant (P < 0.05). See Table 19 for details. Fig.19 .

[0287] Table 19 Comparison of the overall efficacy of TCM syndromes in the two groups of patients (n)

[0288]

[0289] Note: The total effective rate of TCM syndromes in the two groups was compared using Fisher's exact test.

[0290] 5.2 Comparison of total TCM syndrome scores between the two groups before and after treatment

[0291] The total scores of TCM syndromes of the 60 subjects finally included were statistically analyzed, and the results showed that the differences before and after treatment were in line with the normal distribution, so the t-test could be used for analysis. The results showed that the mean score of the experimental group before treatment was 12.97±2.30, and the mean score of the control group was 12.67±2.55. The results showed that there was no statistical difference in the total scores of TCM syndromes between the two groups of patients (P>0.05), and they were comparable. However, after one week of treatment with different regimens, the mean score of the difference before and after treatment in the experimental group was 6.10±2.28, and the mean score of the control group was 3.67±2.17, showing a significant statistical difference (P<0.01). For specific statistical results, please see Table 20. Fig. 20 .

[0292] Table 20 Comparison of total TCM syndrome scores between the two groups of patients before and after treatment

[0293]

[0294] 5.3 Comparison of total TCM syndrome scores between the two groups before and after treatment

[0295] The total scores of TCM symptoms in the two groups of patients before and after treatment were in accordance with normal distribution, and t-test analysis was used. The results showed that after one week of treatment with different regimens, the total scores of TCM symptoms in the two groups of patients were significantly different from those before treatment (P < 0.01). See Table 21 for details. Fig.21 .

[0296] Table 21 Comparison of total scores of TCM syndromes between the two groups of patients before and after treatment

[0297]

[0298] 5.4 Comparison of TCM syndrome scores

[0299] The TCM syndrome scores of the 60 subjects finally included were statistically analyzed. It was found that after one week of treatment with different schemes, the TCM symptom scores of the experimental group were significantly different from those before treatment (P < 0.01). The scores of loose stools, cold pain in the navel and abdomen, fullness in the abdomen, soreness of the waist and knees, and fatigue and laziness in the control group were significantly different from those before treatment (P < 0.01). Fatigue and weakness were significantly different from those before treatment (P < 0.05). There was no statistical difference in body coldness and cold limbs compared with those before treatment (P > 0.05). After treatment, the scores of various syndromes between the two groups were statistically different in loose stools, cold pain in the navel and abdomen, fullness in the abdomen, fatigue and weakness, body coldness and cold limbs, and soreness of the waist and knees (P < 0.05), but there was no statistical difference in fatigue and laziness (P > 0.05). See Table 22 and Figure 22 for details. (The comparison of TCM syndrome scores was conducted using the non-parametric rank sum test)

[0300] Table 22 Comparison of AAD symptom scores between the two groups of patients before and after treatment

[0301]

[0302]

[0303] 4. Comparison of recurrence rate and safety

[0304] 1. Comparison of recurrence rates

[0305] After 1 week of treatment, the patients in both groups who were effectively treated were followed up. Among them, 22 cases in the experimental group were successfully followed up, of which 4 relapsed and 18 did not relapse, with an overall relapse rate of 18.18%. In the control group, 15 cases were successfully followed up, of which 8 relapsed and 7 did not relapse, with an overall relapse rate of 53.33%. The relapse rates of the two groups were compared, and the difference was statistically significant (P < 0.05), indicating that there was a difference in the short-term efficacy (about 1 week) of AAD treatment between the Chinese medicine treatment group and the Western medicine control group. See Table 23 for details. Fig.23 .

[0306] Table 23 Comparison of recurrence rates between the two groups (n)

[0307]

[0308]

[0309] Note: The recurrence rates of the two groups were compared using Fisher's exact test.

[0310] 2. Security comparison

[0311] During the one-week trial, the vital signs of all subjects remained within the normal range, and no obvious abnormalities were found in the three major routine tests, liver and kidney function, and routine electrocardiograms before or after treatment. At the same time, no adverse reactions occurred during the entire trial.

[0312] 3. Analysis of Research Results

[0313] 1. Comparison of basic conditions of patients

[0314] A total of 62 patients with critically ill antibiotic-associated diarrhea were included in this study, and 60 patients completed the study. The median age of the experimental group was 78 years old, and the median age of the control group was 76.5 years old. It can be seen that the age of patients in both the control group and the experimental group was generally older, which may be related to the decline in organ function and poor overall health of the elderly, often accompanied by multiple chronic diseases. These factors, coupled with the widespread problems of weakened gastrointestinal motility and insufficient blood supply to the gastrointestinal tract, make them more likely to encounter intestinal microbiota imbalance when using broad-spectrum antibiotics, thereby increasing the risk of gastrointestinal dysfunction. Traditional Chinese medicine believes that the spleen and stomach of the elderly are weak, unable to normally receive the essence of water and grain, insufficient kidney yang, and unable to warm up. The two yin cannot open and close normally. The combination of the two causes dysfunction of ascending and descending, and the clear and turbid are not distinguished. They are mixed and go down and cause diarrhea. In general, the samples of this study were all from the emergency intensive care unit of Zhejiang Provincial Tongde Hospital. The number of samples is small. Although it cannot represent the overall demographic characteristics of patients with critically ill antibiotic-associated diarrhea, it still has certain reference value.

[0315] 2. Comparative analysis of overall efficacy

[0316] 2.1 Comparative analysis of total symptom scores of AAD

[0317] After 1 week of different treatments, the AAD symptom scores of both groups of patients improved significantly, and this improvement was statistically significant (P < 0.05). Comparing the treatment effects of the two groups, the overall effective rate of the experimental group reached 83.30%, while that of the control group was 60.00%. Further analysis showed that the effective rate of the experimental group was significantly better than that of the control group (P < 0.05). This fully demonstrates that montmorillonite powder combined with probiotics and Zengsun Zhenren Yangzang Decoction can effectively relieve diarrhea symptoms, but Zengsun Zhenren Yangzang Decoction performed better in overall efficacy.

[0318] Montmorillonite powder, a commonly used antidiarrheal drug in clinical practice, has a fixing and inhibitory effect on viruses, bacteria and toxins produced in the digestive tract. In addition, it can strengthen the defense ability of the mucosal barrier and resist the invasion of external attack factors. Bifidobacterium triple live capsule can regulate intestinal flora, improve dysbacteriosis, optimize gastrointestinal function and promote gastrointestinal peristalsis. From the perspective of traditional Chinese medicine, both have the effect of strengthening the body and stopping diarrhea, similar to ginseng and other drugs. Zengsun Zhenren Yangzang Decoction adds drugs that warm the kidney and spleen, harmonize the stomach and detoxify on the basis of strengthening the body and stopping diarrhea, so the antidiarrheal effect is better. From the perspective of modern pharmacology, drugs such as ginseng, angelica, and white peony have the effect of regulating human immunity. Nutmeg, terminalia chebula, and costus root can reduce the expression of inflammatory factors and protect the gastrointestinal mucosa. Cinnamon and pomegranate peel can have a good antibacterial effect. The whole prescription can play an anti-inflammatory and antibacterial role, regulate immunity, and thus promote the recovery of intestinal function. Therefore, the efficacy is better than that of the Western medicine control group.

[0319] 2.2 Comparative analysis of symptom scores

[0320] After one week of treatment with different schemes, the scores of each symptom in the experimental group showed significant statistical differences compared with those before treatment (P < 0.01), indicating that Zengsun Zhenren Yangzang Decoction has a good effect in improving the number of diarrhea, stool characteristics, abdominal pain, bowel sounds, dehydration and other symptoms. The number of diarrhea, stool characteristics, abdominal pain, and bowel sounds in the control group showed significant statistical differences compared with those before treatment (P < 0.01), and the dehydration appearance showed statistical differences compared with those before treatment (P < 0.05), indicating that montmorillonite powder combined with probiotics can also improve the number of diarrhea, stool characteristics, abdominal pain, bowel sounds and dehydration symptoms. Further comparison of the symptom scores of the two groups after treatment showed that the number of diarrhea, stool characteristics, abdominal pain, and bowel sounds showed statistical differences (P < 0.05), while there was no statistical difference in dehydration appearance (P > 0.05). It shows that Zengsun Zhenren Yangzang Decoction is superior to montmorillonite powder combined with probiotics in terms of pain relief and diarrhea relief.

[0321] 3. Comparative analysis of gastrointestinal dysfunction scores

[0322] After one week of treatment with different regimens, the gastrointestinal dysfunction scores of the experimental group after treatment showed significant differences compared with those before treatment (P < 0.01), while there was no statistically significant difference in the scores of the control group before and after treatment (P > 0.05). In addition, there was also a significant statistical difference in the gastrointestinal dysfunction scores between the experimental group and the control group after treatment (P < 0.05). This shows that the experimental group is better than the control group in improving overall gastrointestinal function in the short term. At present, pharmacology has shown that drugs such as ginseng, angelica, and white atractylodes can regulate the body's immune system, repair gastrointestinal mucosal damage, and protect the gastrointestinal tract. In addition, white atractylodes, white peony, and licorice can improve intestinal flora, and cinnamon and pomegranate peel have antibacterial and anti-inflammatory effects. As a compound prescription, Zengsun Zhenren Yangzang Decoction can both take care of the "positive" and eliminate the "evil", so compared with the Western medicine control group, the overall improvement of gastrointestinal function is more obvious.

[0323] 4. Comparative analysis of APACHE II scores

[0324] After one week of treatment with different regimens, the APACHE II scores of both groups were improved compared with before (P < 0.05), and the APACHE II scores of both groups were significantly reduced (P < 0.01), and there was a statistically significant difference between the experimental group and the control group after treatment (P < 0.05). This shows that both treatment methods can improve the overall condition of patients to a certain extent, and the experimental group is better than the control group in improving the overall condition of patients. It can be seen that the clinical efficacy of Zengsun Zhenren Yangzang Decoction in improving the overall condition of patients is better than that of montmorillonite powder combined with probiotics, which reflects the advantages of the holistic view of traditional Chinese medicine. While helping to regulate the spleen and kidneys, consolidate and stop diarrhea, it also nourishes the five internal organs, so that the functions of the internal organs are coordinated and the evil is removed and the body is at peace.

[0325] 5. Comparative analysis of TCM syndrome efficacy

[0326] 5.1 Comparative analysis of total score of TCM syndromes

[0327] After one week of treatment with different regimens, the total score of TCM syndrome in both groups was improved compared with that before (P < 0.05), and there was a significant difference between the two groups (P < 0.01). The overall effective rate of TCM syndrome in the experimental group was 86.70%, and that in the control group was 50.00%, with a significant difference between the two groups (P < 0.01), indicating that both treatments had an improvement effect on TCM syndrome, but the overall efficacy of Zengsun Zhenren Yangzang Decoction was better than that of Western medicine. Comparing the efficacy of TCM syndrome scores in the experimental group and the control group, it can be found that the overall effective rate of TCM syndrome in the experimental group was higher than that in the control group. While affirming the clinical efficacy of Zengsun Zhenren Yangzang Decoction, it is also related to the inclusion of indicators related to spleen and kidney deficiency and cold in TCM syndrome, such as "fear of cold and cold limbs" and "fatigue and fatigue", which is the development of the TCM theory that the spleen governs transportation and transformation and the kidney governs excretion, and it is also the embodiment of the therapeutic effect of Zengsun Zhenren Yangzang Decoction that emphasizes the invigoration of qi and nourishment of zang organs. This also suggests that most of our critically ill patients with antibiotic-associated diarrhea have the commonality of spleen and kidney deficiency and cold.

[0328] 5.2 Comparative analysis of various syndrome scores in traditional Chinese medicine

[0329] After one week of treatment with different treatment schemes, the TCM symptom scores of the experimental group showed significant statistical differences compared with those before treatment (P < 0.01), indicating that Zengsun Zhenren Yangzang Decoction has a good therapeutic effect in improving symptoms such as loose stools, cold pain in the navel and abdomen, fullness in the epigastric and abdominal distension, fatigue, cold body and limbs, soreness of the waist and knees, and fatigue and laziness. In the control group, there were significant statistical differences in loose stools, cold pain in the navel and abdomen, fullness in the epigastrium and abdomen, soreness of the waist and knees, and fatigue and laziness compared with before treatment (P < 0.01), and there was a statistical difference in fatigue compared with before treatment (P < 0.05). There was no statistical difference in cold body and cold limbs compared with before treatment (P > 0.05). This shows that montmorillonite powder combined with probiotics has a good therapeutic effect on improving the symptoms of loose stools, cold pain in the navel and abdomen, fullness in the epigastrium and abdomen, soreness of the waist and knees, and fatigue and laziness, and has a certain effect on improving the symptom of fatigue, but is almost ineffective for cold body and cold limbs. This suggests that in critically ill patients, the improvement of diarrhea symptoms is related to spleen and kidney yang deficiency, and the improvement of diarrhea will bring about the improvement of related symptoms. After treatment, the two groups showed statistically significant differences in the scores of various symptoms, including loose stools, cold pain in the navel and abdomen, fullness in the epigastric region, fatigue, cold body and limbs, and soreness of the waist and knees (P < 0.05), while there was no statistical difference in fatigue and laziness (P > 0.05). This further shows that patients with critically ill antibiotic-associated diarrhea have a common pathogenesis - spleen and kidney deficiency and coldness, and Zengsun Zhenren Yangzang Decoction can greatly improve the patients' TCM symptoms.

[0330] It can be seen from this that: under the guidance of traditional Chinese medicine theory, traditional Chinese medicine syndrome differentiation and treatment has a good effect on improving the traditional Chinese medicine symptoms of spleen and kidney deficiency and cold syndrome in critical antibiotic-associated diarrhea. Zengsun Zhenren Yangzang Decoction is a clinical practice prescription established by the inventor of this application, Professor Chen Mingxian, based on the characteristics of treating both the symptoms and the root cause, and combining astringency with communication. Since the diarrhea in this study was caused by the use of antibiotics, the inventor of this application, Professor Chen Mingxian, believes that the root cause of this disease is inseparable from the bitter and cold nature of the antibiotics themselves. This study shows that antibiotic-associated diarrhea is particularly common in elderly critically ill patients. Most of these patients have weakened yang energy due to long-term diseases, and after long-term combined use of antibiotics, they often experience persistent diarrhea symptoms.

[0331] When the inventor of this application, Professor Chen Mingxian, deeply analyzed the pathological mechanism of critically ill patients, he particularly emphasized their physical characteristics of weak constitution and imbalance of yin and yang. Due to the long-term invasion of diseases, the body functions of these patients have been seriously damaged. In addition, the long-term use of antibiotics has directly broken the yang energy, making the originally weak body even more overwhelmed. In this state, the functions of the three internal organs of the kidney, spleen and stomach are prone to imbalance. The deficiency of kidney yang is not solid and astringent, and the fire of the gate of life is weak and does not warm the middle earth, which further aggravates the symptoms of deficiency and cold in the body. The damage of spleen yang and the disharmony of stomach are the key links in this pathological process. The spleen is responsible for transportation and transformation, and the stomach is responsible for reception. The two coordinate with each other and jointly maintain the digestion and absorption function of the human body. However, in critically ill patients, due to the damage of spleen yang, the function of transportation and transformation of water and grain is imbalanced, resulting in the inability to transform water and grain, and the inability to distinguish between clear and turbid. At the same time, the disharmony of stomach also makes the stomach qi go up, further disrupting the normal function of the body. In this case, the application of Zengsun Zhenren Yangzang Decoction is particularly important. This prescription is based on regulating and replenishing the functions of the spleen, stomach and kidney, and uses both attack and replenishment. It is guided by the treatment principles of "replenishing the weak", "warming the cold" and "astringing the slippery", aiming to replenish qi and activate blood circulation, warm the kidney and strengthen the spleen, astringe the intestines to stop diarrhea, and harmonize the stomach and detoxify. Through this series of treatment principles, Zengsun Zhenren Yangzang Decoction can restore the normal operation of qi, blood, yin and yang throughout the body, thereby achieving the effects of strengthening the spleen and stomach, warming the kidney yang, and stopping diarrhea and dysentery. During the treatment process, we must not only pay close attention to the relief of the patient's symptoms, but also pay attention to adjusting their body functions and improving their own immunity to promote their physiological state to return to normal. Only by taking a comprehensive approach can we truly achieve both symptomatic and root treatment, thereby achieving a profound and lasting therapeutic effect.

[0332] 6. Comparative analysis of recurrence rate

[0333] The recurrence rate of the experimental group was 18.18%, and the recurrence rate of the control group was 53.33%; the difference between the two was statistically significant (P < 0.05), indicating that Zengsun Zhenren Yangzang Decoction has better short-term efficacy in the treatment of critical antibiotic-associated diarrhea. It also shows that Zengsun Zhenren Yangzang Decoction has grasped the key etiology and pathogenesis of spleen and kidney yang deficiency in critically ill patients, fundamentally solved the problem, regulated the body's function, and enhanced the body's anti-infection ability, thereby reducing the recurrence rate of the disease, improving the prognosis of the disease and improving the quality of life of patients.

[0334] 7. Comparative safety analysis

[0335] During the one-week study, no adverse events occurred. The vital signs of all subjects fluctuated within the normal range, and there were no obvious abnormalities in the three routine tests, liver and kidney function, and electrocardiogram before and after treatment. This shows that Zengsun Zhenren Yangzang Decoction, Montmorillonite Powder, and Bifidobacterium Triple Live Bacteria Capsules are relatively safe and reliable. Considering that the number of cases included in this study is small, it does not mean that Zengsun Zhenren Yangzang Decoction is absolutely safe and has no side effects. Further pharmacological research or expanded clinical trials can be conducted to clarify the relevant adverse reactions and provide reference for subsequent promotion and application.

[0336] The above is a description of the embodiments of the present invention. Through the above description of the disclosed embodiments, professionals and technicians in the field can implement or use the present invention. Various modifications to these embodiments will be apparent to professionals and technicians in the field. The general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments shown in this article, but will conform to the widest range consistent with the principles and novelties disclosed herein.

Claims

1. The application of Zengsun Zhenren Yangzang Decoction in the preparation of a drug for treating critical antibiotic-associated diarrhea. The active ingredient raw materials of the Zengsun Zhenren Yangzang Decoction include the following raw materials by weight: 13-17 parts of ginseng, 13-17 parts of angelica charcoal, 18-22 parts of stir-fried Atractylodes macrocephala, 13-17 parts of nutmeg, 5-7 parts of cinnamon, 8-12 parts of roasted licorice, 18-22 parts of stir-fried white peony root, 8-12 parts of stewed costusroot, 8-12 parts of stewed Terminalia chebula, and 18-22 parts of pomegranate peel.

2. The use according to claim 1, characterized in that: The active ingredients of the Zengsun Zhenren Yangzang Decoction include the following ingredients by weight: 15 parts of ginseng, 15 parts of angelica charcoal, 20 parts of stir-fried Atractylodes macrocephala, 15 parts of nutmeg, 6 parts of cinnamon, 10 parts of roasted licorice, 20 parts of stir-fried white peony root, 10 parts of stewed costusroot, 10 parts of stewed Terminalia chebula, and 20 parts of pomegranate peel.

3. The use according to claim 1 or 2, characterized in that: The application includes the treatment of critical antibiotic-associated diarrhea characterized by spleen and kidney deficiency and cold syndrome.

4. The use according to claim 1 or 2, characterized in that: The medicine also includes adding other Chinese herbal medicine extracts and / or adding other raw materials.

5. The use according to claim 1 or 2, characterized in that: The medicine is in the form of tablets, chewable tablets, powders, granules, granules, capsules, ointments, pills or liquid preparations.

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