A Chinese medicine suppository for treating acute pancreatitis and its preparation method

Abstract

The invention discloses a Chinese medicine suppository for treating acute pancreatitis and a preparation method thereof, and belongs to the field of traditional Chinese medicine. The Chinese medicine suppository comprises the following raw materials in parts by weight: 28-35 parts of rhubarb, 28-32 parts of knotweed, 5-12 parts of senna, 5-15 parts of dandelion, 5-12 parts of radix scutellariae, 5-12 parts of radix scutellariae, 5-15 parts of scutellariae, 5-15 parts of scutellariae, 5-15 parts of borneol and 1-2 parts of borneol. Animal experiments and clinical practice confirm that the Chinese medicine suppository prepared by the present invention can significantly alleviate the clinical symptoms and serum indicators of patients with acute pancreatitis, provide new therapeutic drugs and selections for treating acute pancreatitis, and have the value of extensive promotion and application.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine, and particularly to a traditional Chinese medicine suppository for treating acute pancreatitis and a preparation method thereof. Background Art

[0002] Acute pancreatitis refers to an acute abdominal disease characterized by local inflammatory reaction of the pancreas, which is caused by abnormal activation of pancreatic enzymes resulting in digestion of the pancreas itself and surrounding organs, and in severe cases can lead to organ dysfunction. Its typical symptoms are persistent severe pain in the upper abdomen with acute onset, often radiating to the back, accompanied by abdominal distension, nausea, and vomiting, and the pain does not relieve after vomiting. At present, the main treatment principles for acute pancreatitis are symptomatic supportive treatments such as fasting, fluid replacement, inhibition of pancreatic secretion, inhibition of pancreatic enzyme activity, inhibition of inflammatory reaction, and pain relief. Due to the complex condition of acute pancreatitis, the condition may change at any time during the treatment process, and serious complications such as acute kidney injury, acute respiratory distress syndrome, abdominal compartment syndrome, infectious necrosis, and pancreatic duct rupture may occur. Its treatment still has problems such as high mortality and poor prognosis. In recent years, with the wide application of traditional Chinese medicine in disease treatment, seeking an efficient, safe, and low-side-effect traditional Chinese medicine treatment method has become a research hotspot.

[0003] In recent years, studies have found that traditional Chinese medicine has unique advantages in the clinical application of preventing and treating acute pancreatitis. Combining with modern diagnosis and treatment means can significantly improve the clinical symptoms of patients, reduce the incidence of complications, and improve the treatment efficiency and prognosis quality. However, the dosage form and usage method of traditional Chinese medicine limit its wide application in clinical practice. For example, in acute pancreatitis, patients often have chemical peritonitis and paralytic ileus, and patients have symptoms such as abdominal pain, abdominal distension, nausea, and vomiting, and need to fast, indwell a gastric tube, and perform gastrointestinal decompression. For the oral administration method, patients often resist due to aggravated abdominal distension and pain; for the commonly used water decoction dosage form of traditional Chinese medicine, the effective components such as laxatives and heat-clearing and detoxifying components in herbal medicines are destroyed after high-temperature decoction, and the ideal effect of traditional Chinese medicine cannot be exerted; for abdominal external application, the effective utilization rate is low; for intravenous infusion, due to the complex components of traditional Chinese medicine and the presence of macromolecular substances, allergic reactions and the like often easily occur. In addition, there are many traditional Chinese medicine prescriptions for treating acute pancreatitis currently disclosed, mostly with different raw material compositions and dosages, which also leads to uneven effects.

[0004] Therefore, developing a new type of traditional Chinese medicine dosage form and formula has important practical significance for improving the efficacy and safety of traditional Chinese medicine. The cold extraction technology of traditional Chinese medicine is a method of extracting the active ingredients of Chinese herbal medicines at low temperature, which can increase their solubility and make them more easily absorbed by the human body. At the same time, the extraction process at low temperature can also reduce oxidation reactions and enzymatic reactions, maintaining the original chemical structure and biological activity of Chinese herbal medicines. It can better retain the active ingredients of Chinese herbal medicines and improve the efficacy of Chinese herbal medicines. Traditional Chinese medicine suppositories are a type of traditional Chinese medicine preparation administered rectally, with advantages such as convenience, safety, and few side effects. Suppositories can be absorbed through the intestinal tract, improving the bioavailability and therapeutic effect of drugs. Based on this, the present invention provides a traditional Chinese medicine suppository for treating acute pancreatitis, aiming to provide a new treatment option for patients with acute pancreatitis. Summary of the Invention

[0005] The object of the present invention is to provide a traditional Chinese medicine suppository for treating acute pancreatitis and its preparation method to solve the problems existing in the above-mentioned prior art. This traditional Chinese medicine suppository can significantly relieve the clinical symptoms and serum indicators of patients with acute pancreatitis, providing a new therapeutic drug and option for the treatment of acute pancreatitis.

[0006] To achieve the above object, the present invention provides the following solutions:

[0007] The present invention provides a traditional Chinese medicine composition for treating acute pancreatitis, which comprises the following raw materials in parts by weight: 28 - 35 parts of Rheum palmatum, 28 - 32 parts of Polygonum cuspidatum, 5 - 12 parts of Senna leaf, 5 - 15 parts of Zanthoxylum nitidum, 5 - 12 parts of Taraxacum mongolicum, 5 - 12 parts of Hypericum japonicum, 5 - 15 parts of Ilex rotunda, 5 - 15 parts of Drymaria diandra and 1 - 2 parts of Borneol.

[0008] Preferably, it comprises the following raw materials in parts by weight: 30 parts of Rheum palmatum, 30 parts of Polygonum cuspidatum, 10 parts of Senna leaf, 10 parts of Zanthoxylum nitidum, 10 parts of Taraxacum mongolicum, 10 parts of Hypericum japonicum, 10 parts of Ilex rotunda, 10 parts of Drymaria diandra and 1 part of Borneol.

[0009] The present invention also provides a traditional Chinese medicine suppository for treating acute pancreatitis, the only active ingredient of which is the above-mentioned traditional Chinese medicine composition.

[0010] Preferably, it further comprises pharmaceutically acceptable carriers and excipients.

[0011] The present invention also provides a preparation method of the above-mentioned traditional Chinese medicine suppository for treating acute pancreatitis, which is characterized by comprising the following steps:

[0012] After washing, cutting and crushing each component of the traditional Chinese medicine composition, it is mixed with cold water for leaching, and the cold extraction liquid is obtained by filtration;

[0013] After the cold extraction liquid is frozen and concentrated, it is poured into a mold to form suppositories, which are then demolded, sealed, and packaged to obtain the traditional Chinese medicine suppositories for treating acute pancreatitis.

[0014] Preferably, during the mixed extraction, the mass-volume ratio of the traditional Chinese medicine composition to the cold water is 1:(4 - 8), and the extraction time is 2 - 4 hours.

[0015] The present invention also provides the application of the traditional Chinese medicine composition or the traditional Chinese medicine suppositories in the preparation of drugs for treating acute pancreatitis.

[0016] In the prescription provided by the present invention, Rheum palmatum is bitter and cold in nature, purging and descending, clearing and draining. It enters the spleen, stomach, large intestine meridians, as well as the heart, liver meridians and blood aspect. It is good at purging the accumulation and heat in the gastrointestinal tract, purging heat and promoting defecation, guiding the pathogenic damp-heat evils out through defecation, promoting bile drainage and relieving jaundice, "removing the firewood from under the pot" and removing the heat-toxicity in the blood aspect to relieve heat-toxicity, dispersing the heat-toxicity and stasis in the blood aspect to promote blood circulation to remove stasis, cool the blood to stop bleeding, and reduce swelling. Modern research shows that this product has various pharmacological effects such as increasing intestinal peristalsis, promoting defecation, anti-acute pancreatitis, anti-pathogenic microorganisms, anti-renal failure, liver protection, choleresis, anti-ulcer, hemostasis, anti-fibrosis, lipid-lowering, anti-atherosclerosis, anti-inflammatory, and anti-tumor. Polygonum cuspidatum has a slightly bitter and slightly cold taste. It belongs to the liver, gallbladder, and lung meridians. It has the effects of promoting diuresis and relieving jaundice, clearing heat and detoxifying, dispersing stasis and relieving pain, and relieving cough and resolving phlegm. Modern research shows that this product contains free anthraquinones and anthraquinone glycosides, stilbene glycosides, polysaccharides, amino acids and other components, and has effects such as purgation, analgesia, improving microcirculation, antioxidant, anti-pathogenic microorganisms, and anti-tumor. Senna leaf has a sweet, bitter, and cold taste. It belongs to the large intestine meridian. It is bitter and cold, purging and descending, sweet in taste and sticky and slippery in texture, entering the large intestine meridian. It not only purges heat and promotes defecation, guiding the water-damp-heat toxins out, but also promotes diuresis and relieves edema, and has the functions of helping digestion and eliminating food accumulation. Its effect is similar to that of Rheum palmatum, and its power of purging heat and clearing the intestines is also strong. It is good at lubricating the large intestine, and has the advantages of being effective, inexpensive, convenient, simple, not bitter in taste and easy to take. This product contains bisanthrone components, and a small amount of free anthraquinone components, rhein, aloe-emodin, chrysophanol, etc. are also found in Cassia acutifolia Delile. It has various pharmacological effects such as purgation, antibacterial, hemostasis, spasmolysis, and anti-gastric mucosal injury. Zanthoxylum nitidum is a local medicinal material in Guangxi, and has the effects of promoting blood circulation to remove stasis, promoting qi circulation and relieving pain, dispelling wind and dredging collaterals, and detoxifying and reducing swelling. It is commonly used to treat traumatic injuries, rheumatic arthralgia, toothache, stomachache and other diseases. The chemical components of Zanthoxylum nitidum mainly include alkaloids, coumarins, lignans, flavonoids, etc., and have pharmacological activities such as anti-inflammatory analgesia, antibacterial, and anti-tumor. Taraxacum mongolicum Hand.-Mazz. is a commonly used plant in folk medicine and food homology. It has a sweet, slightly bitter, and cold taste. It belongs to the liver and stomach meridians, and has the effects of diuresis, mild purgation, jaundice reduction, and choleresis. It can be used for heat-toxicity, carbuncles, sores, internal carbuncles, red and swollen eyes, damp-heat, jaundice, dysuria with pain, furuncles and carbuncles, breast abscess, scrofula, toothache, red eyes, sore throat, lung abscess, intestinal abscess, damp-heat jaundice, and dysuria with pain. Hypericum japonicum Thunb. is a commonly used herbal medicine in Guangxi folk, and has the effects of clearing heat and detoxifying, promoting diuresis and relieving jaundice, and reducing swelling and dispersing stasis. It is used for damp-heat jaundice, intestinal abscess, red and swollen eyes, and heat-toxic sores. Modern research shows that this product has anti-ulcer effects, purgation, and antibacterial effects. Ilex rotunda Thunb. is also a commonly used herbal medicine in Guangxi folk, and has the effects of clearing heat and detoxifying, promoting diuresis, and relieving pain. It is commonly used in folk to treat cold and fever, tonsillitis, sore throat, acute and chronic hepatitis, acute gastroenteritis, gastric and duodenal ulcers, rheumatic joint pain, traumatic injury, and scald. Modern research shows that this product has hemostasis, relaxes intestinal smooth muscle and can antagonize the intestinal spasm caused by acetylcholine and antibacterial effects. Drymaria diandra Blume can clear heat and detoxify, promote diuresis and defecation, and also has the effect of promoting blood circulation and reducing swelling. It is usually used orally in folk to treat acute hepatitis, stomachache, malaria, ascites, and externally applied to treat fractures, sores and boils, and snake bites.Borneol (Dryobalanops aromatica Gaertn. f.) is pungent, bitter, and slightly cold in nature; it acts on the heart, liver, and lung meridians; with its delicate fragrance and dispersing property, it has the effects of resuscitating the consciousness and clearing away heat and toxins. It is mainly used to treat high fever and coma due to febrile diseases, stroke with phlegm syncope and convulsions, summer dampness blocking the clear orifices, sore throat and deafness, aphtha and tooth swelling, sores, carbuncles, infantile malnutrition and hemorrhoids, and red and swollen eyes. Borneol can be easily absorbed through mucous membranes and subcutaneous tissues, and is excreted from the body after binding with glucuronic acid in the body. In animal experiments, when mice were intragastrically administered with 3H-borneol at a dose of 1 μCi / (g body weight), it could be rapidly absorbed through the intestinal mucosa. Five minutes after administration, it could penetrate the blood-brain barrier and had a relatively high concentration and a long residence time in the central nervous system. Its resuscitating effect may be related to this. Borneol can maintain a relatively high blood drug concentration in the blood for a long time, is rapidly eliminated by the liver and kidneys, and is not easily accumulated. When administered by gavage at a dose of 3.5 μCi / animal, the half-absorption period was 0.157 hours and the absorption coefficient was 0.25, indicating relatively poor bioavailability; the elimination half-life was 5.3 hours and it was not easily accumulated. In the present invention, the main active ingredients of Rheum palmatum, Polygonum cuspidatum, and Senna leaf are mainly anthraquinones and anthraquinone glycosides, which are easily soluble in water. If the decocting time is too long, most of the anthra glycosides will be destroyed. Therefore, when exerting the effects of clearing and purging, and purging heat and relieving constipation, it is not suitable for long decocting. Low-temperature extraction of Zanthoxylum nitidum, Taraxacum mongolicum, Hypericum japonicum, Ilex rotunda, and Drymaria cordata can reduce oxidation reactions and enzymatic reactions and maintain the original chemical structure and biological activity of Chinese herbal medicines. Therefore, in the present invention, Rheum palmatum, Polygonum cuspidatum, Senna leaf, Zanthoxylum nitidum, Taraxacum mongolicum, Hypericum japonicum, Ilex rotunda, Drymaria cordata, and borneol (Dryobalanops aromatica Gaertn. f.) are combined and made into a Chinese medicine suppository through a cold extraction technique. Rheum palmatum and Polygonum cuspidatum purge heat and relieve constipation, clear and purge, disperse stasis and relieve pain, and are the monarch drugs; Senna leaf purges heat and relieves constipation, and guides out dampness, heat, and toxins, and is the ministerial drug; Zanthoxylum nitidum, Taraxacum mongolicum, Hypericum japonicum, Ilex rotunda, and Drymaria cordata clear heat and detoxify, have anti-inflammatory, analgesic, and anti-infective effects, and are the adjuvant drugs; Borneol is pungent, bitter, with a delicate fragrance and dispersing property, and is easily absorbed through mucous membranes and subcutaneous tissues, and is the messenger drug; when all the drugs are combined and through the cold extraction technique, the active ingredients of Chinese herbal medicines are maximally retained. Through rectal administration, it can be rapidly absorbed, exert the effects of purging heat and relieving constipation, clearing heat and detoxifying, relieving pain, and promoting blood circulation to remove stasis, and is used to relieve symptoms such as abdominal distension, abdominal pain, and constipation in patients with acute pancreatitis, control the inflammatory reaction, reduce peritoneal effusion, prevent infection, and restore intestinal function.

[0017] The present invention discloses the following technical effects:

[0018] Through clinical practice and scientific proportioning, the present invention enables each medicinal material to play a synergistic role in the suppository and improves the therapeutic effect. At the same time, considering the interaction between medicinal materials and the individual differences of patients, the proportion of medicinal materials has been optimized and adjusted many times. Finally, the optimal proportion combination obtained is: 30 parts of Rheum palmatum, 30 parts of Polygonum cuspidatum, 10 parts of Senna leaf, 10 parts of Zanthoxylum nitidum, 10 parts of Taraxacum mongolicum, 10 parts of Hypericum japonicum, 10 parts of Ilex rotunda, 10 parts of Drymaria cordata, and 1 part of borneol.

[0019] This suppository is made from traditional Chinese medicinal materials with the effects of purging heat and promoting defecation, clearing heat and detoxifying, relieving pain, promoting blood circulation and removing stasis, etc. It is made through scientific proportioning and processing, and has the advantages of convenience, safety, and few side effects. At the same time, the manufacturing process has been optimized through cold extraction technology to improve the dissolution rate, release rate, and bioavailability of the suppository. Clinical trials have proved that the total effective rate of this traditional Chinese medicine suppository is 100%, and it has significant curative effects and safety in the treatment of acute pancreatitis. This lays a foundation for further optimizing the formula and manufacturing process of the suppository in the future, improving the treatment effect and the comfort of patients, and at the same time has important significance for promoting the wide application and development of traditional Chinese medicine suppositories in clinical practice. Brief Description of the Drawings

[0020] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required to be used in the embodiments. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.

[0021] Figure 1 Effect of traditional Chinese medicine suppository on serum amylase activity (A) and serum pancreatic lipase content (B);

[0022] Figure 2 Effect of traditional Chinese medicine suppository on the expression of pro-inflammatory factor IL-6mRNA;

[0023] Figure 3 Effect of traditional Chinese medicine suppository on the expression of pro-inflammatory factor TNF-αmRNA;

[0024] Figure 4 Effect of traditional Chinese medicine suppository on the expression of anti-inflammatory factor IL-10mRNA. Detailed Embodiments

[0025] Now, various exemplary embodiments of the present invention will be described in detail. This detailed description should not be considered as a limitation of the present invention, but should be understood as a more detailed description of certain aspects, characteristics, and implementation schemes of the present invention.

[0026] It should be understood that the terms described in the present invention are only for describing specific embodiments and are not used to limit the present invention. In addition, for the numerical ranges in the present invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any intermediate value within any stated value or stated range, as well as each smaller range between any other stated value or intermediate value within the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded from the range.

[0027] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In case of conflict with any incorporated document, the content of this specification shall prevail.

[0028] Without departing from the scope or spirit of the present invention, various modifications and variations can be made to the specific embodiments of the present invention specification, which are obvious to those skilled in the art. Other embodiments obtained from the specification of the present invention are obvious to those skilled in the art. The specification and examples of the present invention are merely exemplary.

[0029] Regarding the use of "comprising", "including", "having", "containing", etc. herein, they are all open-ended terms, meaning including but not limited to.

[0030] Traditional Chinese medicine believes that acute pancreatitis is mostly caused by overeating, long-standing biliary diseases, and invasion of exogenous pathogens, leading to the generation of damp-heat in the liver, gallbladder, and stomach. The accumulation of damp-heat causes qi stagnation, obstruction of collaterals, and blockage of the qi movement in the bowels, resulting in abdominal distension, pain, and fullness. "Blockage of the qi movement in the bowels" is a highly generalized pathogenesis, so "promoting defecation and purging the interior" is the basic principle. Currently, Chinese herbal enemas with laxative effects such as rhubarb are clinically used to effectively relieve abdominal distension symptoms. However, due to the acute onset of acute pancreatitis, it takes time to prepare the enema decoction temporarily, which will delay treatment. Moreover, the enema traditional Chinese medicine with only laxative effects cannot achieve the purpose of relieving pain and inhibiting the inflammatory response. In addition, the commonly used water decoction dosage form of traditional Chinese medicine cannot exert the ideal effect of traditional Chinese medicine because the effective components of purgation and clearing heat and detoxifying in herbal medicines are destroyed after high-temperature decoction. Furthermore, the dosage of the traditional Chinese medicine enema solution is difficult to control, the operation is cumbersome, and it requires a dedicated person for enema, etc. To solve the above problems, in clinical practice, the traditional Chinese medicine suppository provided by the present invention can be quickly administered by inserting it into the anus, and the operation is simple. The main materials of the traditional Chinese medicine suppository include rhubarb, polygonum cuspidatum, senna leaf, zanthoxylum nitidum, dandelion, hypericum japonicum, ilicistriloba, drymaria diandra, and borneol (borneol). In the present invention, the main effective components in rhubarb, polygonum cuspidatum, and senna leaf are mainly anthraquinones and anthraquinone glycosides, which are easily soluble in water. If the decoction time is too long, most of the anthra glycosides will be destroyed. Therefore, when exerting the functions of clearing and purging, and purging heat and promoting defecation, it is not suitable for long decoction. Zanthoxylum nitidum, dandelion, hypericum japonicum, ilicistriloba, and drymaria diandra can reduce oxidation reactions and enzymatic reactions by low-temperature extraction, and maintain the original chemical structure and biological activity of Chinese herbal medicines. Therefore, the present invention combines rhubarb, polygonum cuspidatum, senna leaf, zanthoxylum nitidum, dandelion, hypericum japonicum, ilicistriloba, drymaria diandra with borneol (borneol), and prepares a traditional Chinese medicine suppository through a cold extraction technology. The traditional Chinese medicine suppository has the effects of promoting defecation, relieving distension, relieving pain, clearing heat and detoxifying, promoting blood circulation and removing blood stasis, anti-inflammatory, inhibiting inflammation, and preventing infection, and can significantly relieve the clinical symptoms and serum indexes of patients with acute pancreatitis. The following will be further described specifically by way of examples.

[0031] Example 1 A traditional Chinese medicine suppository for treating acute pancreatitis

[0032] The traditional Chinese medicine suppository comprises the following raw materials: 30 g of rhubarb, 30 g of polygonum cuspidatum, 10 g of senna leaf, 10 g of zanthoxylum nitidum, 10 g of dandelion, 10 g of hypericum japonicum, 10 g of ilicistriloba, 10 g of drymaria diandra, and 1 g of borneol.

[0033] The preparation method of the traditional Chinese medicine suppository comprises: cleaning, cutting, and crushing the raw materials of rhubarb, polygonum cuspidatum, senna leaf, zanthoxylum nitidum, dandelion, hypericum japonicum, ilicistriloba, drymaria diandra, and borneol, then mixing them with 6 times the volume of water and soaking for 3 h, filtering and separating the medicinal materials and the soaking solution to obtain a cold extraction solution; then performing freeze concentration, pouring it into a mold (the inner wall of the mold is pre-coated with glyceryl monostearate to facilitate demolding), demolding, sealing, and packaging to obtain the product.

[0034] Example 2 A traditional Chinese medicine suppository for treating acute pancreatitis

[0035] The traditional Chinese medicine suppository comprises the following raw materials: 28 g of Rheum officinale, 28 g of Polygonum cuspidatum, 5 g of Senna leaf, 5 g of Zanthoxylum nitidum, 8 g of Taraxacum mongolicum, 5 g of Hypericum japonicum, 9 g of Ilex rotunda, 5 g of Drymaria diandra and 1.5 g of borneol.

[0036] The preparation method is the same as that of Example 1.

[0037] Example 3 A traditional Chinese medicine suppository for treating acute pancreatitis

[0038] The traditional Chinese medicine suppository comprises the following raw materials: 32 g of Rheum officinale, 30 g of Polygonum cuspidatum, 8 g of Senna leaf, 10 g of Zanthoxylum nitidum, 10 g of Taraxacum mongolicum, 8 g of Hypericum japonicum, 5 g of Ilex rotunda, 9 g of Drymaria diandra and 1 g of borneol.

[0039] The preparation method is the same as that of Example 1.

[0040] Example 4 A traditional Chinese medicine suppository for treating acute pancreatitis

[0041] The traditional Chinese medicine suppository comprises the following raw materials: 35 g of Rheum officinale, 32 g of Polygonum cuspidatum, 12 g of Senna leaf, 15 g of Zanthoxylum nitidum, 12 g of Taraxacum mongolicum, 12 g of Hypericum japonicum, 15 g of Ilex rotunda, 15 g of Drymaria diandra and 2 g of borneol.

[0042] The preparation method is the same as that of Example 1.

[0043] Application example:

[0044] 1. Animal experiment

[0045] 1.1 Establishing an animal model of acute pancreatitis

[0046] Twenty 20 - 23 g male C57BL / 6J mice at about 8 weeks old were randomly divided into a control group, a model group and a traditional Chinese medicine suppository treatment group (using the traditional Chinese medicine suppository prepared in Example 1). Mice in the control group, the model group and the traditional Chinese medicine suppository treatment group were injected with normal saline (0.90%) and caerulein (100 μg / kg) by intraperitoneal injection; the injection was given once an hour for 8 consecutive times. During the experiment period, the three groups of mice were fed with the same feed. Except for the traditional Chinese medicine suppository group which was given rectal administration for 4 days before caerulein-induced modeling, twice a day, one suppository each time. After the last injection, the mice were injected with a lethal dose of sodium pentobarbital and the samples were collected quickly.

[0047] 1.2 Index detection

[0048] (1) HE staining

[0049] Fresh pancreas and colon were taken and immersed in 4% paraformaldehyde for dehydration, embedded in paraffin and sectioned. The sections were stained with HE and then the degree of tissue pathological damage was observed under an optical microscope (Leica, Germany).

[0050] (2) Detection of serum amylase level

[0051] Amylase can hydrolyze starch to produce glucose, maltose and dextrin. When the substrate concentration is known and in excess, adding iodine solution forms a blue complex with the unhydrolyzed starch. According to the depth of the blue color, the amount of hydrolyzed starch can be calculated, and thus the activity of serum amylase can be calculated. The present invention uses a serum amylase kit to detect the content of serum amylase in the serum during the occurrence of acute pancreatitis.

[0052] The results are as Figure 1 shown in A. The serum amylase activity in the model group was significantly increased compared with the normal group, and the serum amylase activity in the traditional Chinese medicine suppository group was significantly decreased compared with the model group (P<0.01). Therefore, it shows that the traditional Chinese medicine suppository prepared by the present invention can down-regulate the amylase activity in mice with acute pancreatitis.

[0053] Mouse serum pancreatic lipase was measured using an ELISA kit. Pancreatic lipase was added to the enzyme-labeled wells pre-coated with monoclonal antibody against mouse pancreatic lipase for incubation, then biotin-labeled anti-pancreatic lipase antibody was added, and then combined with avidin-HRP to form a complex. After incubation and washing to remove the unbound enzyme, substrates A and B were added, producing a blue color and converted to yellow under the action of acid. The color depth is positively correlated with the concentration of pancreatic lipase in the serum sample.

[0054] The results are as Figure 1 shown in B. The results showed that compared with the control group, the pancreatic lipase in the model group was significantly increased, while after intervention with the traditional Chinese medicine suppository, the content of serum pancreatic lipase was significantly decreased (P<0.01), indicating that the traditional Chinese medicine suppository can down-regulate the content of serum pancreatic lipase in mice with acute pancreatitis.

[0055] (3) Detection of inflammatory factors

[0056] The mRNA expression levels of inflammatory factors IL-6, TNF-α and IL-10 in mouse pancreatic tissue were measured using a fluorescence quantitative PCR (qPCR) kit.

[0057] (4) Results and analysis

[0058] The HE staining results showed that: in the control group, the pancreatic tissue structure was dense without obvious cracks; in the model group, vacuoles and death of acinar cells were significantly observed in the mouse pancreatic tissue, and a large number of inflammatory cells infiltrated, and obvious damage to the pancreatic tissue was present; while in the traditional Chinese medicine suppository treatment group, the conditions of vacuoles and death of acinar cells, infiltration of a large number of inflammatory cells and damage to the pancreatic tissue were significantly improved.

[0059] The fluorescence quantitative detection results are as Figures 2 - 4As shown, the results showed that compared with the control group, the mRNA levels of IL-6 and TNF-α in the model group were significantly increased, while IL-10 was significantly decreased (P<0.01). After the intervention treatment with traditional Chinese medicine suppository, the mRNA levels of IL-6 and TNF-α in the traditional Chinese medicine suppository treatment group were significantly decreased, while IL-10 was significantly increased (P<0.01). It shows that traditional Chinese medicine suppository can significantly improve the serum inflammatory indexes of mice with acute pancreatitis.

[0060] 2. Clinical trials

[0061] 2.1 Data

[0062] All 40 patients were patients with acute pancreatitis admitted to the First Affiliated Hospital of Guangxi University of Chinese Medicine. They were randomly divided into a control group and a traditional Chinese medicine suppository treatment group, with 20 patients in each group. There was no significant difference in age, gender, etc. between the two groups of patients.

[0063] 2.2 Diagnostic criteria

[0064] All cases met the diagnostic criteria for acute pancreatitis in the "Diagnosis and Treatment Guidelines for Acute Pancreatitis in China 2021".

[0065] 2.3 Inclusion criteria

[0066] (1) The clinical characteristics met the diagnostic criteria for acute pancreatitis;

[0067] (2) Patients admitted within 72 hours after the onset of the disease.

[0068] 2.4 Exclusion criteria

[0069] (1) Having severe primary diseases of the cardiovascular, liver, kidney, endocrine, and hematopoietic systems;

[0070] (2) Having severe mental diseases that require long-term drug maintenance treatment;

[0071] (3) Being pregnant or lactating women;

[0072] (4) Being allergic to traditional Chinese medicine ingredients;

[0073] (5) Patients with ARDS, shock, coma, or those who need to be transferred to the surgical department for treatment at the time of admission.

[0074] 2.5 Treatment methods

[0075] Both groups of patients were routinely given fasting and water deprivation, gastrointestinal decompression, intravenous nutritional support, maintenance of water, electrolyte, and acid-base balance, protection of important organs to prevent multiple organ failure, correction of hypoxemia, maintenance of blood glucose stability, and anti-infection treatment.

[0076] In the control group, somatostatin at a dosage of 250 μg / h was continuously infused to inhibit pancreatic enzyme secretion, and a one-week treatment course was defined as one cycle. On the basis of the treatment in the control group, the treatment group was given the traditional Chinese medicine suppository of Example 1 via rectal administration, twice a day, one suppository each time, and a one-week treatment course was defined as one cycle.

[0077] 2.6 Efficacy evaluation criteria

[0078] Marked effect: Clinical symptoms disappeared;

[0079] Effective: Symptoms were significantly relieved;

[0080] Ineffective: Clinical symptoms were not significantly relieved.

[0081] Table 1 Recovery time of clinical signs and symptoms after treatment in the control group and the traditional Chinese medicine suppository group days)

[0082]

[0083] Note: Compared with the control group, *P < 0.05

[0084] As shown in Table 1, when comparing the improvement of clinical symptoms between the two groups, the results showed that: in the traditional Chinese medicine suppository group, the recovery time of bowel sounds, exhaust and defecation was significantly shortened, and the disappearance time of abdominal pain and distension symptoms in the traditional Chinese medicine suppository group was also significantly better than that in the control group (P < 0.05). It shows that the traditional Chinese medicine suppository can significantly relieve the clinical symptoms of patients with acute pancreatitis.

[0085] Table 2 Comparison of changes in inflammatory factors before and after treatment in the control group and the traditional Chinese medicine suppository group

[0086]

[0087] Note: Compared with the control group, *P < 0.05

[0088] As shown in Table 2, when comparing the changes in the levels of inflammatory factors between the two groups, the results showed that: before treatment, there was no significant difference in the levels of inflammatory factors between the two groups (P > 0.05). After 14 days of treatment, the expression levels of TNF-α, IL-6, and IL-β in the control group were higher than those in the traditional Chinese medicine suppository group (P < 0.05).

[0089] The results in Table 1 and Table 2 above show that there are significant differences in the statistical results of various indicators between the control group and the traditional Chinese medicine suppository group, indicating that the traditional Chinese medicine suppository prepared by the present invention can relieve the clinical symptoms of patients faster, and can also quickly and effectively inhibit the level of inflammatory response and reduce the inflammatory response. It shows that the traditional Chinese medicine suppository of the present invention can significantly relieve the clinical symptoms and serum indicators of patients with acute pancreatitis.

[0090] Table 3 Comparison of clinical efficacy between the two groups after 7 days of treatment

[0091]

[0092] Note: Compared with the control group, *P < 0.05

[0093] The total effective rate of the control group was lower than that of the traditional Chinese medicine suppository group (P < 0.05), as shown in Table 3.

[0094] The results of the above Table 1, Table 2 and Table 3 show that the traditional Chinese medicine suppository prepared by this application can effectively treat acute pancreatitis, providing a new dosage form of traditional Chinese medicine that is safe, effective and convenient to use for the treatment of acute pancreatitis.

[0095] The above-described embodiments are only descriptions of the preferred modes of the present invention, and do not limit the scope of the present invention. Without departing from the design spirit of the present invention, various deformations and improvements made by those of ordinary skill in the art to the technical solutions of the present invention shall fall within the protection scope determined by the claims of the present invention.

Claims

1. A Chinese medicine suppository for treating acute pancreatitis, characterized in that: The invention comprises the following raw materials in parts by weight: 28-35 parts of rhubarb, 28-32 parts of knotweed, 5-12 parts of senna leaves, 5-15 parts of zelkova chinensis, 5-12 parts of dandelion, 5-12 parts of rhubarb, 5-15 parts of scutellaria baicalensis, 5-15 parts of scutellaria baicalensis, 5-15 parts of hollyhock root and 1-2 parts of borneol.

2. The Chinese medicine suppository according to claim 1, characterized in that: The invention comprises the following raw materials in parts by weight: 30 parts of rhubarb, 30 parts of knotweed, 10 parts of senna leaves, 10 parts of lanceolate, 10 parts of dandelion, 10 parts of rhubarb, 10 parts of scutellaria baicalensis, 10 parts of scutellaria baicalensis, 10 parts of scutellaria baicalensis and 1 part of borneol.

3. The Chinese medicine suppository according to claim 1, characterized in that: Also included are pharmaceutically acceptable carriers.

4. A method for preparing the Chinese medicine suppository according to any one of claims 1 to 3, characterized in that: The following steps are involved: The components of the Chinese medicine composition are washed, cut, and crushed, mixed with cold water for extraction, and filtered to obtain a cold extract; After freezing and concentrating the cold extract, pouring it into a mold to form a suppository, demoulding, sealing and packaging, a Chinese medicine suppository for treating acute pancreatitis is obtained; The inner wall of the mold is pre-coated with mixed fatty acid glyceride.

5. The preparation method according to claim 4, characterized in that: During the mixed extraction, the mass volume ratio of the traditional Chinese medicine composition to the cold water is 1:(4-8), and the extraction time is 2-4h.

6. Use of the Chinese medicine suppository according to any one of claims 1 to 3 in the preparation of a medicament for treating acute pancreatitis.

Images