A traditional Chinese medicine composition for treating klebsiella pneumoniae pneumonia and a preparation method thereof

Abstract

The application belongs to the technical field of traditional Chinese medicines, and particularly discloses a traditional Chinese medicine composition for treating Klebsiella pneumoniae pneumonia and a preparation method thereof. The traditional Chinese medicine composition is prepared from eight raw medicinal materials of Zhejiang fritillary bulb, white mulberry bark, Chinese plume-pod seed, dandelion, platycodon root, lily, apricot kernel and poria cocos. The composition has the effects of promoting lung and clearing heat, relieving cough and reducing sputum, and strengthening body resistance and eliminating pathogenic factors. Pharmacodynamic experiments show that the composition has a significant therapeutic effect on Klebsiella pneumoniae pneumonia.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition for treating Klebsiella pneumoniae pneumonia and its preparation method. Background Technology

[0002] Pneumonia is an infectious inflammation of the alveoli, distal airways, and pulmonary interstitium. It is commonly caused by bacteria, viruses, and other pathogens. The main clinical manifestations of pneumonia include fever, cough, sputum production, wheezing, and hemoptysis, which may be accompanied by chest pain or dyspnea. Bacterial pneumonia is the most common type of pneumonia and one of the most prevalent infectious diseases. Epidemiological surveys show that Klebsiella pneumoniae infection accounts for 3.8% of community-acquired pneumonia cases and 8.3%-15.4% of hospital-acquired pneumonia cases. The widespread use of broad-spectrum antibiotics has led to a year-on-year increase in drug resistance in Klebsiella pneumoniae. Furthermore, the multifaceted and extensive resistance of this bacterium makes treatment extremely difficult and significantly increases patient mortality.

[0003] Klebsiella pneumoniae is a genus of Gram-negative bacilli belonging to the family Enterobacteriaceae. It can be divided into three subspecies: Klebsiella pneumoniae (also known as Klebsiella pneumoniae), Klebsiella odorinae, and Klebsiella rhinosclerotiorum. Klebsiella pneumoniae was first isolated from the sputum of patients with lobar pneumonia in 1882 by Friedlander, who initially named it Friedlander bacillus. In 1886, it was renamed Klebsiella pneumoniae, KP. KP has a thick capsule, mostly possesses pili, lacks spores and flagella, and is non-motile. It is widely distributed in natural environments such as soil and surface water, and readily colonizes the mucous membranes of the gastrointestinal tract and oropharynx, as well as other parts of the human body.

[0004] Klebsiella pneumoniae (KP) is widely distributed in nature and is a component of the normal human microbiota. However, in immunocompromised individuals, those with malignant tumors, and those with underlying diseases, it can become a pathogen causing opportunistic infections, and is one of the common pathogens causing nosocomial and community-acquired infections. Based on its pathogenic characteristics, KP is further divided into classic Klebsiella pneumoniae (cKP) and hypervirulent Klebsiella pneumoniae (hvKP). cKP is a common pathogen causing nosocomial infections, often colonizing the oral cavity, skin, digestive tract mucosa, and surfaces of medical equipment. In immunocompromised individuals with diabetes and malignant tumors, it can cause severe pneumonia, urinary tract infections, and respiratory infections. hvKP, on the other hand, is more likely to cause community-acquired infections, commonly seen in healthy young individuals, and is more prone to causing invasive infections such as liver abscess, endophthalmitis, brain abscess, and fasciitis.

[0005] Klebsiella pneumoniae infection causes pneumonia primarily because the bacteria trigger a series of inflammatory responses upon entering the body, activating transcription factors and increasing the levels of chemokines and inflammatory factors. Excessive secretion of these inflammatory factors can damage the lung parenchyma, leading to pneumonia. Previous studies have shown that Klebsiella pneumoniae infection can trigger multiple inflammatory pathways, promoting the secretion of inflammatory factors such as IL-6, IL-β, and TNF-α, and activating the NLRP3 inflammasome. Therefore, inhibiting the levels of inflammatory factors and inflammatory cells is an effective method for treating bacterial pneumonia caused by Klebsiella pneumoniae infection.

[0006] Currently, commonly used drugs for treating Klebsiella pneumoniae infection include carbapenems (imipenem, meropenem), β-lactams, quinolones, and aminoglycosides. However, in recent years, with the emergence of multidrug-resistant (MDR) and even extensively drug-resistant (XDR) bacteria, the resistance rate has gradually increased. Therefore, exploring new methods for treating Klebsiella pneumoniae pneumonia has significant clinical importance and practical value. Summary of the Invention

[0007] Given that antibiotics used in the clinical treatment of Klebsiella pneumoniae pneumonia infection are prone to drug resistance, the purpose of this invention is to provide a traditional Chinese medicine composition for treating Klebsiella pneumoniae pneumonia infection. The composition of this invention has the effects of clearing the lungs and resolving phlegm, strengthening the body's resistance and eliminating pathogenic factors, and can effectively treat Klebsiella pneumoniae pneumonia.

[0008] A traditional Chinese medicine composition for treating Klebsiella pneumoniae pneumonia infection is made from Fritillaria thunbergii, Morus alba root bark, Lepidium apetalum seed, Taraxacum mongolicum, Platycodon grandiflorus, Lilium brownii, Prunus armeniaca seed, and Poria cocos.

[0009] Preferably, the traditional Chinese medicine composition is made from the following traditional Chinese medicine components:

[0010] Fritillaria thunbergii 20-40 parts by weight, Morus alba root bark 26-46 parts by weight, Lepidium apetalum 20-40 parts by weight

[0011] Dandelion 35-55 parts by weight, Platycodon grandiflorus 20-40 parts by weight, Lilium 26-46 parts by weight

[0012] Bitter almonds 20-40 parts by weight, Poria cocos 35-55 parts by weight

[0013] Preferably, the traditional Chinese medicine composition is made from the following traditional Chinese medicine components:

[0014] Fritillaria thunbergii 25-35 parts by weight, Morus alba root bark 30-40 parts by weight, Lepidium apetalum 25-35 parts by weight

[0015] Dandelion 40-50 parts by weight, Platycodon grandiflorus 25-35 parts by weight, Lily 30-40 parts by weight

[0016] Bitter almonds 25-35 parts by weight, Poria cocos 40-50 parts by weight

[0017] Preferably, the traditional Chinese medicine composition is made from the following traditional Chinese medicine components:

[0018] Fritillaria thunbergii 30 parts by weight, Morus alba root bark 36 parts by weight, Lepidium apetalum 30 parts by weight

[0019] Dandelion 45 parts by weight, Platycodon grandiflorus 30 parts by weight, Lilium 36 parts by weight

[0020] 30 parts by weight of bitter almonds and 45 parts by weight of Poria cocos

[0021] In this formula, Fritillaria thunbergii, bitter and cold in nature, clears the lungs, resolves phlegm, stops cough, and clears heat to disperse stagnation, serving as the principal herb. Morus alba root bark clears the lungs, relieves asthma, and eliminates phlegm; Lepidium apetalum clears the lungs, relieves asthma, and promotes diuresis to reduce swelling. Together, they serve as assistant herbs. Lilium brownii moistens the lungs and stops cough; Prunus armeniaca stops cough and relieves asthma, also serving as assistant herbs. Taraxacum mongolicum, cold in nature and bitter and sweet in taste, clears heat and detoxifies, disperses stagnant qi, and resolves heat toxins; Poria cocos promotes diuresis and eliminates dampness, serving as the main herb for treating phlegm. Together, they serve as adjuvant herbs. Platycodon grandiflorus clears the lungs, eliminates phlegm, and drains pus, acting as a carrier to transport the herbs upwards, serving as the guiding herb. The combined herbs complement and enhance each other, resulting in a doubled effect, working together to clear the lungs, stop cough, resolve phlegm, and strengthen the body's resistance to pathogens. This formula is primarily used to treat Klebsiella pneumoniae pneumonia, addressing both the root cause and symptoms, and consistently yields good results.

[0022] Preferably, the Lepidium seed described in this invention is a stir-fried Lepidium seed.

[0023] Another objective of this invention is to provide an oral preparation containing the above-mentioned traditional Chinese medicine composition and a method for preparing the same, wherein the oral preparation is one of granules, oral liquids, capsules, tablets, pills, micro-pills, microcapsules, soft capsules, powders, mixtures, or syrups.

[0024] The preparation method of the oral Chinese medicine preparation includes the following steps:

[0025] (1) Weigh out eight raw medicinal materials: Fritillaria thunbergii, Morus alba root bark, Lepidium apetalum seed, Taraxacum mongolicum, Platycodon grandiflorus, Lilium brownii, Prunus armeniaca seed, and Poria cocos. Fritillaria thunbergii is cleaned and crushed, Morus alba root bark is cleaned and shredded, Taraxacum mongolicum is cleaned and cut into sections, Platycodon grandiflorus is cleaned and cut into thick slices, Prunus armeniaca seed is cleaned and crushed, Poria cocos is cleaned and cut into pieces, and Lepidium apetalum seed is stir-fried according to the stir-frying method until it pops.

[0026] (2) Take the raw medicinal materials from step (1), add water and decoct 2-3 times, combine the decoctions and concentrate to an extract with a relative density of 1.15-1.25 at 50-60℃, add ethanol for precipitation, let stand, take the supernatant, concentrate, and obtain concentrated solution.

[0027] (3) The concentrate obtained in step (2) is prepared into a clinically acceptable dosage form by adding acceptable excipients or solvents using conventional techniques or methods in the art.

[0028] Preferably, the amount of water added in step (2) is 6-10 times the amount of medicinal materials.

[0029] Preferably, the simmering time in step (2) is 2-3 hours.

[0030] More preferably, in step (2), water is added and decocted twice. The first time, 10 times the amount of water is added and decocted for 2.5-3 hours. The second time, 8 times the amount of water is added and decocted for 1.5-2 hours.

[0031] Preferably, step (2) involves concentrating the combined decoction to an extract with a relative density of 1.15-1.25 at 50-60°C.

[0032] Preferably, in step (2), the alcohol precipitation process is carried out to achieve an alcohol content of 60-80%, and the mixture is left to stand and refrigerate for 12-48 hours.

[0033] Preferably, the conventional techniques or methods in the art described in step (3) include, but are not limited to, water sedimentation, filtration, concentration, spray drying, belt drying, pulverization, sieving, etc.

[0034] Preferably, the acceptable excipients include one or more of fillers, lubricants, preservatives, flavoring agents, disintegrants, binders, colorants, and dispersants.

[0035] Preferably, the pharmaceutically acceptable excipients include, but are not limited to, lactose, starch, dextrin, powdered sugar, magnesium stearate, maltose, lemon juice, tartaric acid, sodium hydroxide, aspartame, steviol glycoside, cyclamate, protein sugar, acesulfame potassium, aspartame, sucralose, etc.

[0036] In one embodiment, the dosage form is granules, and its preparation method includes the following steps:

[0037] 1) Weigh out the following 8 raw medicinal materials: Fritillaria thunbergii, Morus alba root bark, Lepidium apetalum seed, Taraxacum mongolicum, Platycodon grandiflorus, Lilium brownii, Prunus armeniaca seed, and Poria cocos. Among them, Fritillaria thunbergii is cleaned and crushed, Morus alba root bark is cleaned and shredded, Taraxacum mongolicum is cleaned and cut into sections, Platycodon grandiflorus is cleaned and cut into thick slices, Prunus armeniaca seed is cleaned and crushed, Poria cocos is cleaned and cut into pieces, and Lepidium apetalum seed is stir-fried according to the stir-frying method until it pops.

[0038] 2) Take the 8 raw medicinal materials from step 1), add water and decoct twice. The first time, add 10 times the amount of water and decoct for 3 hours. The second time, add 8 times the amount of water and decoct for 2 hours. Combine the decoctions, filter, and concentrate under reduced pressure to an extract with a density of 1.20 at 50-60℃. Add 95% ethanol for precipitation to make the ethanol content reach 70%. Refrigerate for 48 hours, filter, and obtain the filtrate for later use.

[0039] 3) The filtrate from step 2) was concentrated under reduced pressure to a density of 1.35 at 50-60℃, then dried under vacuum using a belt dryer at a vacuum degree of -0.08MPa to 0.10MPa and a drying temperature of 54℃. The filtrate was then pulverized into a fine powder, sieved, and set aside for later use.

[0040] 4) Take 360g of the fine powder from step 3), add an appropriate amount of dextrin and sucrose to make 1000g, mix well, dry granulate, granulate, and package to obtain granules.

[0041] In one embodiment, the dosage form is an oral liquid, and its preparation method includes the following steps:

[0042] 1) Weigh out the following 8 raw medicinal materials: Fritillaria thunbergii, Morus alba root bark, Lepidium apetalum seed, Taraxacum mongolicum, Platycodon grandiflorus, Lilium brownii, Prunus armeniaca seed, and Poria cocos. Among them, Fritillaria thunbergii is cleaned and crushed, Morus alba root bark is cleaned and shredded, Taraxacum mongolicum is cleaned and cut into sections, Platycodon grandiflorus is cleaned and cut into thick slices, Prunus armeniaca seed is cleaned and crushed, Poria cocos is cleaned and cut into pieces, and Lepidium apetalum seed is stir-fried according to the stir-frying method until it pops.

[0043] 2) Take the 8 raw medicinal materials from step 1), decoct them twice with water. The first time, add 10 times the amount of water and decoct for 3 hours. The second time, add 8 times the amount of water and decoct for 2 hours. Combine the decoctions, filter, and concentrate under reduced pressure to an extract with a relative density of 1.22 at 50-60℃. Add 95% ethanol for precipitation to make the ethanol content reach 60%. Refrigerate for 24 hours, filter, and obtain the filtrate for later use.

[0044] 3) Concentrate the filtrate from step 2) under reduced pressure to a concentration of 1.33 at 50-60℃, add 6 times the amount of water, refrigerate for 48 hours, filter, concentrate the filtrate under reduced pressure to an appropriate amount, add an appropriate amount of sucrose or aspartame, stir to dissolve, adjust the pH to 7.0, add water to the total volume, stir, filter, fill, and sterilize to obtain the oral liquid preparation.

[0045] In another embodiment, the dosage form is a capsule, and its preparation method includes the following steps:

[0046] 1) Weigh out the following 8 raw medicinal materials: Fritillaria thunbergii, Morus alba root bark, Lepidium apetalum seed, Taraxacum mongolicum, Platycodon grandiflorus, Lilium brownii, Prunus armeniaca seed, and Poria cocos. Among them, Fritillaria thunbergii is cleaned and crushed, Morus alba root bark is cleaned and shredded, Taraxacum mongolicum is cleaned and cut into sections, Platycodon grandiflorus is cleaned and cut into thick slices, Prunus armeniaca seed is cleaned and crushed, Poria cocos is cleaned and cut into pieces, and Lepidium apetalum seed is stir-fried according to the stir-frying method until it pops.

[0047] 2) Take the 8 raw medicinal materials from step 1), add water and decoct 3 times. The first time, add 9 times the amount of water and decoct for 3 hours. The second time, add 7 times the amount of water and decoct for 2 hours. The third time, add 6 times the amount of water and decoct for 1.5 hours. Combine the decoctions, filter, and concentrate under reduced pressure to an extract with a density of 1.23 at 50-60℃. Add 95% ethanol for precipitation to make the ethanol content reach 75%. Refrigerate for 36 hours, filter, and obtain the filtrate for later use.

[0048] 3) The filtrate in step 2) is concentrated under reduced pressure to a concentrated solution with a density of 1.33 at 50 - 60 °C, spray-dried, pulverized into fine powder, sieved, and reserved for use.

[0049] 4) Add the above-mentioned fine powder to an appropriate amount of starch, dextrin, and sucrose, mix well to form coarse granules, dry, pulverize, sieve, dry at low temperature, size the granules, add an appropriate amount of magnesium stearate, mix well, and fill into capsule shells to obtain the capsule preparation.

[0050] The third object of the present invention is to provide the use of the traditional Chinese medicine composition in the preparation of a drug for treating Klebsiella pneumoniae pneumonia.

[0051] To verify the effect of the traditional Chinese medicine composition of the present invention in treating Klebsiella pneumoniae pneumonia, the inventors carried out corresponding animal experimental studies and clinical studies. It should be noted that the samples selected for the animal experimental studies are those obtained from the representative formula of the present invention and its preparation method. Due to space limitations, the experiments and results of the products obtained from other formulas and preparation methods included in the present invention are not listed in detail herein.

[0052] Experimental Example 1 Influence of the Traditional Chinese Medicine Composition on the Pneumonia Model of Mice Infected with Klebsiella pneumoniae

[0053] 1 Experimental Materials

[0054] 1.1 Experimental Animals

[0055] 60 BALB / c mice, SPF grade, weighing (20 ± 2) g, with half males and half females, 6 - 8 weeks old, provided by Lunan Pharmaceutical Group Co., Ltd., and the experimental animal certificate number is SYXK (Lu) 2018 - 0008. The animals were housed in separate cages in a dedicated laboratory, and the housing environmental conditions were room temperature 20 - 25 °C, relative humidity 40% - 60%, natural light, and free access to food and water.

[0056] 1.2 Instruments, Reagents, and Drugs

[0057] AG285 electronic analytical balance (Mettler-Toledo, Switzerland), GL-20A fully automatic refrigerated high-speed centrifuge (Centrifuge Factory, Hunan Instrument and Meter General Factory), low-temperature high-speed centrifuge (Eppendorf, Germany), tissue grinder (Jieling Instrument Manufacturing Tianjin Co., Ltd.), -80℃ ultra-low temperature freezer (Qingdao Haier Co., Ltd.), IL-6, IL-1β, TNF-α ELISA kit (Xinbosheng Biotechnology Co., Ltd.), Klebsiella pneumoniae (Beina Chuanglian Biotechnology Co., Ltd.), chloral hydrate (Beijing Beihua Fine Chemicals Co., Ltd.), physiological saline (Chenxin Pharmaceutical Co., Ltd.), positive control drug was levofloxacin (Shandong Qidu Pharmaceutical Co., Ltd.), and the test drug was a granule sample prepared according to the formulation and preparation method in Example 1.

[0058] 2. Experimental Methods

[0059] 2.1 Grouping and Model Establishment: Sixty BALB / c mice were randomly divided into six groups: a normal control group, a Klebsiella pneumoniae pneumonia model control group, a positive control group, a high-dose experimental group, a medium-dose experimental group, and a low-dose experimental group, with 10 mice in each group (half male and half female). After acclimatization for 3 days, model establishment began, with fasting for 12 hours prior to model establishment. All animals were anesthetized by intraperitoneal injection of 0.35 mL / 100 g of 10% chloral hydrate. After obvious anesthesia symptoms appeared, 40 μL of chloral hydrate containing approximately 10% chloral hydrate was instilled into each group. 7 A suspension of Klebsiella pneumoniae in the logarithmic growth phase (with the nostrils plugged during instillation) was administered to allow the inoculum to enter the lungs. The normal control group received 40 μL of sterile saline via the same method. After inoculation, mice were held in a position perpendicular to the table for 30 seconds to ensure the bacterial solution flowed into the lung tissue due to gravity, and then placed in cages.

[0060] 2.2 Administration: The dosage for each group was calculated based on the weight of the mice and converted to the equivalent adult daily dose. The high, medium and low dose groups of traditional Chinese medicine were administered 10g / kg / d, 5g / kg / d and 2.5g / kg / d of traditional Chinese medicine by gavage, respectively, which were equivalent to 2 times, 1 times and 1 / 2 times the commonly used human clinical dose, respectively. The positive control group was administered levofloxacin 0.3g / kg / d by gavage, and the normal control group and the pneumococcal model control group were administered an equal volume of physiological saline by gavage. All were administered by gavage once a day for 5 consecutive days.

[0061] 2.3 Detection Indicators and Methods:

[0062] (1) Measurement of serum indicators: Two hours after the last administration, blood was collected from the eyeballs and placed in EP tubes. After the blood coagulated naturally at room temperature for 30 minutes, it was centrifuged at 3000 r / min for 20 minutes at 4℃ to separate the serum. The serum was then aliquoted and frozen at -80℃. The levels of IL-6, TNF-α, and IL-1β inflammatory factors in mice after bacterial infection were measured by ELISA. The specific steps were strictly performed in accordance with the reagent instructions.

[0063] (2) Determination of lung index: After removing the eyeballs, the mice were euthanized. The lung tissue was removed, rinsed with ice-cold physiological saline, and after rinsing, the surface moisture was absorbed with filter paper. The weight was accurately measured and the lung index was calculated.

[0064]

[0065] (3) Measurement of lung tissue indicators: After weighing, homogenize the tissue with a tissue homogenizer, centrifuge and collect the supernatant. Store at -80℃ and detect the IL-6 and TNF-α content. Strictly follow the ELISA kit instructions to detect the IL-6 and TNF-α content.

[0066] ˉ

[0067] 2.4 Statistical methods: SPSS 19.0 statistical software was used for analysis. Experimental data are expressed as mean ± standard deviation (x ± s). One-way ANOVA was used to compare differences between groups, and P < 0.05 was considered statistically significant.

[0068] 3 Experimental Results

[0069] 3.1 Lung Index

[0070] The experimental results showed that, compared with the normal control group, the lung index of the Klebsiella pneumoniae infection model control group was significantly increased (p<0.05), indicating that the Klebsiella pneumoniae infection model in mice was successfully established. The Klebsiella pneumoniae infection model control group, the positive control group, and the high, medium, and low dose groups all significantly reduced the lung index induced by Klebsiella pneumoniae infection in mice, and the differences were statistically significant (P<0.05). The results are shown in Table 1.

[0071] Table 1. Effects on lung index in a mouse model of pneumonia induced by Klebsiella pneumoniae infection.

[0072]

[0073] Note: Compared with the normal control group: P < 0.05 is indicated by "*"; compared with the model control group: P < 0.05 is indicated by "#".

[0074] 3.2 Results of serum IL-6, TNF-α, and IL-1β levels

[0075] The experimental results showed that, compared with the normal control group, the serum levels of IL-6, TNF-α, and IL-1β in mice in the Klebsiella pneumoniae infection model control group were significantly increased, and the differences were statistically significant (P < 0.05), indicating that the model was successfully established. Compared with the model control group, the serum levels of IL-6, TNF-α, and IL-1β in mice in the levofloxacin positive control group and the high, medium, and low dose groups were significantly decreased, and the differences were statistically significant (P < 0.05); the results are shown in Table 2.

[0076] Table 2. Results of serum IL-6, TNF-α, and IL-1β levels (pg / mL). )

[0077]

[0078] Note: Compared with the normal control group: P < 0.05 is indicated by "*"; compared with the model control group: P < 0.05 is indicated by "#".

[0079] TNF-α can interact with a variety of cytokines and can synergize with IL-1 to activate nuclear factor kappa B in inflammatory lung cells and induce the production of cytokines such as IL-6. IL-1β can stimulate the production of a variety of chemokines and participate in the repair of damaged alveolar epithelium, but its main function is pro-inflammatory. IL-6 is an important acute-phase response mediator in the body's trauma and repair process and has a pro-inflammatory effect.

[0080] 3.3 Results of determination of IL-6 and TNF-α levels in lung tissue homogenate

[0081] The experimental results showed that, compared with the normal control group, the levels of IL-6 and TNF-α in the lung tissue homogenate of mice in the Klebsiella pneumoniae infection model control group were significantly increased, and the differences were statistically significant (P < 0.05), indicating that the model was successfully established. Compared with the model control group, the levels of IL-6 and TNF-α in the serum of mice in the levofloxacin positive control group and the high, medium, and low dose groups were significantly decreased, and the differences were statistically significant (P < 0.05); the results are shown in Table 3.

[0082] The above results indicate that Klebsiella pneumoniae infection in mice leads to a significant increase in IL-6 and TNF-α levels, resulting in significant pathological damage to lung tissue. Gavage administration of a traditional Chinese medicine composition can improve the levels of inflammatory factors in mice and reduce the infiltration and damage of Klebsiella pneumoniae to lung tissue, thus demonstrating a definite therapeutic effect on Klebsiella pneumoniae-induced pneumonia.

[0083] Table 3. Results of IL-6 and TNF-α content determination in lung tissue supernatant (pg / mL). )

[0084]

[0085]

[0086] Note: Compared with the normal control group: P < 0.05 is indicated by "*"; compared with the model control group: P < 0.05 is indicated by "#".

[0087] IL-1β can induce fever by acting on the hypothalamus, exhibiting a strong pyrogenic effect and promoting the progression of Klebsiella pneumoniae pneumonia. IL-6 can aggregate neutrophils, damaging lung tissue and thus worsening the condition of pneumonia patients. TNF-α can promote the secretion of other inflammatory factors, triggering a cascade of inflammatory responses in the body, thereby exacerbating inflammatory damage to lung tissue. Experimental results showed that medium and high doses of the traditional Chinese medicine composition significantly reduced the levels of IL-6, IL-1β, and TNF-α in mouse serum, and significantly reduced the levels of IL-6 and TNF-α in lung tissue homogenate.

[0088] In summary, the traditional Chinese medicine composition of the present invention can effectively reduce the levels of inflammatory factors in serum and lung tissue supernatant, inhibit inflammatory response, restore lung function, and thus have a significant therapeutic effect on Klebsiella pneumoniae pneumonia. Detailed Implementation

[0089] To enable those skilled in the art to fully understand the present invention, the present invention is further illustrated below through specific embodiments. However, those skilled in the art should understand that the embodiments of the present invention do not limit the present invention in any way.

[0090] Example 1: Preparation of Granules

[0091] Fritillaria thunbergii 300g, Morus alba root bark 360g, Lepidium apetalum 300g

[0092] Dandelion 450g, Platycodon grandiflorus 300g, Lily bulb 360g

[0093] 300g bitter almonds, 450g Poria cocos

[0094] 1) Weigh out the following 8 raw medicinal materials: Fritillaria thunbergii, Morus alba root bark, Lepidium apetalum seed, Taraxacum mongolicum, Platycodon grandiflorus, Lilium brownii, Prunus armeniaca seed, and Poria cocos. Among them, Fritillaria thunbergii is cleaned and crushed, Morus alba root bark is cleaned and shredded, Taraxacum mongolicum is cleaned and cut into sections, Platycodon grandiflorus is cleaned and cut into thick slices, Prunus armeniaca seed is cleaned and crushed, Poria cocos is cleaned and cut into pieces, and Lepidium apetalum seed is stir-fried according to the stir-frying method until it pops.

[0095] 2) Take the 8 raw medicinal materials from step 1), add water and decoct twice. The first time, add 10 times the amount of water and decoct for 3 hours. The second time, add 8 times the amount of water and decoct for 2 hours. Combine the decoctions, filter, and concentrate under reduced pressure to an extract with a density of 1.20 at 50-60℃. Add 95% ethanol for precipitation to make the ethanol content reach 70%. Refrigerate for 48 hours, filter, and obtain the filtrate for later use.

[0096] 3) The filtrate from step 2) was concentrated under reduced pressure to a density of 1.35 at 50-60℃, then dried under vacuum using a belt dryer at a vacuum degree of -0.08MPa to 0.10MPa and a drying temperature of 54℃. The filtrate was then pulverized into a fine powder, sieved, and set aside for later use.

[0097] 4) Take 360g of the fine powder from step 3), add an appropriate amount of dextrin and sucrose to make 1000g, mix well, dry granulate, granulate, and package to obtain granules.

[0098] Example 2: Preparation of Tablets

[0099] Fritillaria thunbergii 200g, Morus alba root bark 460g, Lepidium apetalum 200g

[0100] Dandelion 550g, Platycodon grandiflorus 200g, Lily bulb 460g

[0101] 200g bitter almonds, 550g Poria cocos

[0102] 1) Weigh out the following 8 raw medicinal materials: Fritillaria thunbergii, Morus alba root bark, Lepidium apetalum seed, Taraxacum mongolicum, Platycodon grandiflorus, Lilium brownii, Prunus armeniaca seed, and Poria cocos. Among them, Fritillaria thunbergii is cleaned and crushed, Morus alba root bark is cleaned and shredded, Taraxacum mongolicum is cleaned and cut into sections, Platycodon grandiflorus is cleaned and cut into thick slices, Prunus armeniaca seed is cleaned and crushed, Poria cocos is cleaned and cut into pieces, and Lepidium apetalum seed is stir-fried according to the stir-frying method until it pops.

[0103] 2) Take the 8 raw medicinal materials from step 1), add water and decoct twice. The first time, add 8 times the amount of water and decoct for 3 hours. The second time, add 6 times the amount of water and decoct for 2 hours. Combine the decoctions, filter, and concentrate under reduced pressure to an extract with a density of 1.15 at 50-60℃. Add 95% ethanol for precipitation to make the ethanol content reach 60%. Refrigerate for 24 hours, filter, and obtain the filtrate for later use.

[0104] 3) The filtrate from step 2) was concentrated under reduced pressure to a density of 1.30 at 50-60℃, then dried under vacuum using a belt dryer at a vacuum degree of -0.08MPa to 0.10MPa and a drying temperature of 54℃. The filtrate was then pulverized into a fine powder, sieved, and set aside for later use.

[0105] 4) Take the above fine powder, add an appropriate amount of microcrystalline cellulose, starch, and magnesium stearate, mix well, and compress into tablets.

[0106] Example 3: Preparation of Capsules

[0107] Fritillaria thunbergii 400g, Morus alba root bark 260g, Lepidium apetalum 400g

[0108] Dandelion 550g, Platycodon grandiflorus 200g, Lily bulb 460g

[0109] 200g bitter almonds, 350g Poria cocos

[0110] 1) Weigh out the following 8 raw medicinal materials: Fritillaria thunbergii, Morus alba root bark, Lepidium apetalum seed, Taraxacum mongolicum, Platycodon grandiflorus, Lilium brownii, Prunus armeniaca seed, and Poria cocos. Among them, Fritillaria thunbergii is cleaned and crushed, Morus alba root bark is cleaned and shredded, Taraxacum mongolicum is cleaned and cut into sections, Platycodon grandiflorus is cleaned and cut into thick slices, Prunus armeniaca seed is cleaned and crushed, Poria cocos is cleaned and cut into pieces, and Lepidium apetalum seed is stir-fried according to the stir-frying method until it pops.

[0111] 2) Take the 8 raw medicinal materials from step 1), add water and decoct 3 times. The first time, add 9 times the amount of water and decoct for 3 hours. The second time, add 7 times the amount of water and decoct for 2 hours. The third time, add 6 times the amount of water and decoct for 1.5 hours. Combine the decoctions, filter, and concentrate under reduced pressure to an extract with a density of 1.23 at 50-60℃. Add 95% ethanol for precipitation to make the ethanol content reach 75%. Refrigerate for 36 hours, filter, and obtain the filtrate for later use.

[0112] 3) The filtrate from step 2) is concentrated under reduced pressure to a density of 1.33 at 50-60℃, spray-dried, pulverized into fine powder, sieved, and set aside for later use;

[0113] 4) Add an appropriate amount of starch, dextrin and sucrose to the above fine powder, mix well, make coarse granules, dry, crush, sieve, dry at low temperature, granulate, add an appropriate amount of magnesium stearate, mix well, and fill into capsule shells to obtain capsules.

[0114] Example 4: Preparation of pills

[0115] Fritillaria thunbergii 250g, Morus alba root bark 400g, Lepidium apetalum 250g

[0116] 500g dandelion, 250g platycodon, 400g lily bulb

[0117] 250g bitter almonds, 500g Poria cocos

[0118] 1) Weigh out the following 8 raw medicinal materials: Fritillaria thunbergii, Morus alba root bark, Lepidium apetalum seed, Taraxacum mongolicum, Platycodon grandiflorus, Lilium brownii, Prunus armeniaca seed, and Poria cocos. Among them, Fritillaria thunbergii is cleaned and crushed, Morus alba root bark is cleaned and shredded, Taraxacum mongolicum is cleaned and cut into sections, Platycodon grandiflorus is cleaned and cut into thick slices, Prunus armeniaca seed is cleaned and crushed, Poria cocos is cleaned and cut into pieces, and Lepidium apetalum seed is stir-fried according to the stir-frying method until it pops.

[0119] 2) Take the 8 raw medicinal materials from step 1), add water and decoct twice. The first time, add 10 times the amount of water and decoct for 2.5 hours. The second time, add 8 times the amount of water and decoct for 1.5 hours. Combine the decoctions, filter, and concentrate under reduced pressure to an extract with a density of 1.20 at 50-60℃. Add 95% ethanol for precipitation to make the ethanol content reach 80%. Refrigerate for 12 hours, filter, and obtain the filtrate for later use.

[0120] 3) The filtrate from step 2) was concentrated under reduced pressure to a density of 1.38 at 50-60℃, dried under vacuum using a belt dryer at a vacuum degree of -0.08MPa to 0.10MPa and a drying temperature of 54℃, pulverized into fine powder, sieved, and set aside for later use.

[0121] 4) Add an appropriate amount of starch and microcrystalline cellulose to the above fine powder, mix well, granulate, dry, sizing, and fill into capsule shells to obtain capsules.

[0122] Example 5: Preparation of Syrup

[0123] Fritillaria thunbergii 250g, Morus alba root bark 400g, Lepidium apetalum 250g

[0124] Dandelion 350g, Platycodon grandiflorus 250g, Lily bulb 400g

[0125] 400g bitter almonds, 500g Poria cocos

[0126] 1) Weigh out the following 8 raw medicinal materials: Fritillaria thunbergii, Morus alba root bark, Lepidium apetalum seed, Taraxacum mongolicum, Platycodon grandiflorus, Lilium brownii, Prunus armeniaca seed, and Poria cocos. Among them, Fritillaria thunbergii is cleaned and crushed, Morus alba root bark is cleaned and shredded, Taraxacum mongolicum is cleaned and cut into sections, Platycodon grandiflorus is cleaned and cut into thick slices, Prunus armeniaca seed is cleaned and crushed, Poria cocos is cleaned and cut into pieces, and Lepidium apetalum seed is stir-fried according to the stir-frying method until it pops.

[0127] 2) Take the 8 raw medicinal materials from step 1), decoct them twice with water. The first time, add 10 times the amount of water and decoct for 2.5 hours. The second time, add 8 times the amount of water and decoct for 1.5 hours. Combine the decoctions, filter, and concentrate under reduced pressure to an extract with a density of 1.18 at 50-60℃. Add 95% ethanol for precipitation to make the ethanol content reach 80%. Refrigerate for 12 hours, filter, and obtain the filtrate for later use.

[0128] 3) Concentrate the filtrate from step 2) under reduced pressure to a density of 1.31 at 50-60℃, add an appropriate amount of sucrose to dissolve, add purified water to the total volume, stir well and let stand for 24 hours, filter coarsely through a sieve, then filter finely through a microporous membrane, and bottle to obtain the syrup.

[0129] Example 6: Preparation of Oral Liquid

[0130] Fritillaria thunbergii 320g, Morus alba root bark 340g, Lepidium apetalum 320g

[0131] Dandelion 430g, Platycodon grandiflorus 320g, Lily bulb 340g

[0132] 320g bitter almonds, 430g Poria cocos

[0133] 1) Weigh out the following 8 raw medicinal materials: Fritillaria thunbergii, Morus alba root bark, Lepidium apetalum seed, Taraxacum mongolicum, Platycodon grandiflorus, Lilium brownii, Prunus armeniaca seed, and Poria cocos. Among them, Fritillaria thunbergii is cleaned and crushed, Morus alba root bark is cleaned and shredded, Taraxacum mongolicum is cleaned and cut into sections, Platycodon grandiflorus is cleaned and cut into thick slices, Prunus armeniaca seed is cleaned and crushed, Poria cocos is cleaned and cut into pieces, and Lepidium apetalum seed is stir-fried according to the stir-frying method until it pops.

[0134] 2) Take the 8 raw medicinal materials from step 1), decoct them twice with water. The first time, add 10 times the amount of water and decoct for 3 hours. The second time, add 8 times the amount of water and decoct for 2 hours. Combine the decoctions, filter, and concentrate under reduced pressure to an extract with a relative density of 1.22 at 50-60℃. Add 95% ethanol for precipitation to make the ethanol content reach 60%. Refrigerate for 24 hours, filter, and obtain the filtrate for later use.

[0135] 3) Concentrate the filtrate from step 2) under reduced pressure to a concentration of 1.33 at 50-60℃, add 6 times the amount of water, refrigerate for 48 hours, filter, concentrate the filtrate under reduced pressure to an appropriate amount, add an appropriate amount of sucrose or aspartame, stir to dissolve, adjust the pH to 7.0, add water to the total volume, stir, filter, fill, and sterilize to obtain the oral liquid preparation.

[0136] Example 7 Preparation of the mixture

[0137] Fritillaria thunbergii 280g, Morus alba root bark 380g, Lepidium apetalum 280g

[0138] Dandelion 470g, Platycodon grandiflorus 280g, Lily bulb 380g

[0139] 280g bitter almonds, 470g Poria cocos

[0140] 1) Weigh out the following 8 raw medicinal materials: Fritillaria thunbergii, Morus alba root bark, Lepidium apetalum seed, Taraxacum mongolicum, Platycodon grandiflorus, Lilium brownii, Prunus armeniaca seed, and Poria cocos. Among them, Fritillaria thunbergii is cleaned and crushed, Morus alba root bark is cleaned and shredded, Taraxacum mongolicum is cleaned and cut into sections, Platycodon grandiflorus is cleaned and cut into thick slices, Prunus armeniaca seed is cleaned and crushed, Poria cocos is cleaned and cut into pieces, and Lepidium apetalum seed is stir-fried according to the stir-frying method until it pops.

[0141] 2) Take the 8 raw medicinal materials from step 1), add water and decoct twice. The first time, add 10 times the amount of water and decoct for 3 hours. The second time, add 8 times the amount of water and decoct for 2 hours. Combine the decoctions, filter, and concentrate under reduced pressure to an extract with a relative density of 1.25 at 50-60℃. Add 95% ethanol for precipitation to make the ethanol content reach 70%. Refrigerate for 24 hours, filter, and obtain the filtrate for later use.

[0142] 3) Concentrate the filtrate from step 2) under reduced pressure to a concentration with a relative density of 1.31 at 50-60℃, add 7 times the amount of water, refrigerate for 48 hours, filter, concentrate the filtrate under reduced pressure to an appropriate amount, add an appropriate amount of sodium benzoate, stir well, add water to the total volume, and the mixture is obtained.

[0143] Example 8: Preparation of Powder

[0144] Fritillaria thunbergii 300g, Morus alba root bark 360g, Lepidium apetalum 300g

[0145] Dandelion 450g, Platycodon grandiflorus 300g, Lily bulb 260g

[0146] 300g bitter almonds, 450g Poria cocos

[0147] 1) Weigh out the following 8 raw medicinal materials: Fritillaria thunbergii, Morus alba root bark, Lepidium apetalum seed, Taraxacum mongolicum, Platycodon grandiflorus, Lilium brownii, Prunus armeniaca seed, and Poria cocos. Among them, Fritillaria thunbergii is cleaned and crushed, Morus alba root bark is cleaned and shredded, Taraxacum mongolicum is cleaned and cut into sections, Platycodon grandiflorus is cleaned and cut into thick slices, Prunus armeniaca seed is cleaned and crushed, Poria cocos is cleaned and cut into pieces, and Lepidium apetalum seed is stir-fried according to the stir-frying method until it pops.

[0148] 2) Take the 8 raw medicinal materials from step 1) and decoct them twice with water. The first time, add 10 times the amount of water and decoct for 3 hours. The second time, add 8 times the amount of water and decoct for 2 hours. Combine the decoctions, filter, and concentrate under reduced pressure to an extract with a density of 1.21 at 50-60℃. Add 95% ethanol for precipitation to make the ethanol content reach 60%. Refrigerate for 48 hours, filter, and obtain the filtrate for later use.

[0149] 3) The filtrate from step 2) was concentrated under reduced pressure to a density of 1.30 at 50-60℃, then dried under vacuum using a belt dryer at a vacuum degree of -0.08MPa to 0.10MPa and a drying temperature of 54℃. The filtrate was then pulverized into a fine powder, sieved, and an appropriate amount of lactose was added. The mixture was then sieved again and packaged to obtain the powder.

[0150] Example 9: Preparation of Granules

[0151] Fritillaria thunbergii 300g, Morus alba root bark 350g, Lepidium apetalum 300g

[0152] Dandelion 440g, Platycodon grandiflorus 400g, Lily bulb 350g

[0153] 300g bitter almonds, 450g Poria cocos

[0154] 1) Weigh out the following 8 raw medicinal materials: Fritillaria thunbergii, Morus alba root bark, Lepidium apetalum seed, Taraxacum mongolicum, Platycodon grandiflorus, Lilium brownii, Prunus armeniaca seed, and Poria cocos. Among them, Fritillaria thunbergii is cleaned and crushed, Morus alba root bark is cleaned and shredded, Taraxacum mongolicum is cleaned and cut into sections, Platycodon grandiflorus is cleaned and cut into thick slices, Prunus armeniaca seed is cleaned and crushed, Poria cocos is cleaned and cut into pieces, and Lepidium apetalum seed is stir-fried according to the stir-frying method until it pops.

[0155] 2) Take the 8 raw medicinal materials from step 1), add water and decoct twice. The first time, add 9 times the amount of water and decoct for 3 hours. The second time, add 6 times the amount of water and decoct for 2 hours. Combine the decoctions, filter, and concentrate under reduced pressure to an extract with a density of 1.24 at 50-60℃. Add 95% ethanol for precipitation to make the ethanol content reach 70%. Refrigerate for 24 hours, filter, and obtain the filtrate for later use.

[0156] 3) The filtrate from step 2) is concentrated under reduced pressure to a density of 1.31 at 50-60℃, spray-dried, pulverized into fine powder, sieved, and set aside for later use;

[0157] 4) Add appropriate amounts of dextrin and cyclamate to the above fine powder, mix well, add appropriate amount of 75% ethanol to make granules, dry, and granulate to make granules.

[0158] Example 10: Preparation of Microencapsulation Formulation

[0159] Fritillaria thunbergii 350g, Morus alba root bark 300g, Lepidium apetalum 350g

[0160] Dandelion 400g, Platycodon grandiflorus 350g, Lily bulb 300g

[0161] 350g bitter almonds, 400g Poria cocos

[0162] 1) Weigh out the following 8 raw medicinal materials: Fritillaria thunbergii, Morus alba root bark, Lepidium apetalum seed, Taraxacum mongolicum, Platycodon grandiflorus, Lilium brownii, Prunus armeniaca seed, and Poria cocos. Among them, Fritillaria thunbergii is cleaned and crushed, Morus alba root bark is cleaned and shredded, Taraxacum mongolicum is cleaned and cut into sections, Platycodon grandiflorus is cleaned and cut into thick slices, Prunus armeniaca seed is cleaned and crushed, Poria cocos is cleaned and cut into pieces, and Lepidium apetalum seed is stir-fried according to the stir-frying method until it pops.

[0163] 2) Take the 8 raw medicinal materials from step 1), add water and decoct twice. The first time, add 10 times the amount of water and decoct for 3 hours. The second time, add 8 times the amount of water and decoct for 2 hours. Combine the decoctions, filter, and concentrate under reduced pressure to an extract with a density of 1.20 at 50-60℃. Add 95% ethanol for precipitation to make the ethanol content reach 65%. Refrigerate for 24 hours, filter, and obtain the filtrate for later use.

[0164] 3) The filtrate from step 2) is concentrated under reduced pressure to a density of 1.31 at 50-60℃, spray-dried, pulverized into fine powder, sieved, and set aside for later use;

[0165] 4) Take octenyl succinate starch, glyceryl monostearate, titanium dioxide, and propylene glycol, add purified water, heat and stir at 56°C to dissolve, prepare a capsule material solution with a mass fraction of 32%, cool to room temperature, add the formulated amount of fine powder of traditional Chinese medicine composition extract and soybean lecithin while stirring, homogenize and emulsify to obtain an emulsion, spray dry under the conditions of inlet air temperature of 171°C, spray pressure of 0.38MPa, and feed rate of 20ml / min to obtain microcapsules.

Claims

1. A traditional Chinese medicine composition for treating Klebsiella pneumoniae pneumonia, characterized in that, It is made from the following Chinese herbal ingredients: Fritillaria thunbergii 20-40 parts by weight, Morus alba root bark 26-46 parts by weight, stir-fried Lepidium apetalum 20-40 parts by weight Dandelion 35-55 parts by weight, Platycodon grandiflorus 20-40 parts by weight, Lilium 26-46 parts by weight Bitter almonds 20-40 parts by weight, Poria cocos 35-55 parts by weight.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, It is made from the following Chinese herbal ingredients: Fritillaria thunbergii 25-35 parts by weight, Morus alba root bark 30-40 parts by weight, and stir-fried Lepidium apetalum 25-35 parts by weight Dandelion 40-50 parts by weight, Platycodon grandiflorus 25-35 parts by weight, Lily 30-40 parts by weight Bitter almonds 25-35 parts by weight, Poria cocos 40-50 parts by weight.

3. The traditional Chinese medicine composition according to claim 2, characterized in that, It is made from the following Chinese herbal ingredients: Fritillaria thunbergii 30 parts by weight, Morus alba root bark 36 parts by weight, stir-fried Lepidium apetalum 30 parts by weight Dandelion 45 parts by weight, Platycodon grandiflorus 30 parts by weight, Lilium 36 parts by weight 30 parts by weight of bitter almonds and 45 parts by weight of Poria cocos.

4. A traditional Chinese medicine oral preparation for treating Klebsiella pneumoniae pneumonia, characterized in that, The traditional Chinese medicine composition contains any one of the claims 1-3.

5. The oral preparation of traditional Chinese medicine according to claim 4, characterized in that, The oral Chinese medicine preparations mentioned are one of the following: granules, oral liquids, capsules, tablets, pills, micro-pills, microcapsules, powders, mixtures, and syrups.

6. The method for preparing the oral Chinese medicine preparation according to claim 5, characterized in that, Includes the following steps: (1) Weigh out eight raw medicinal materials: Fritillaria thunbergii, Morus alba root bark, Lepidium apetalum seed, Taraxacum mongolicum, Platycodon grandiflorus, Lilium brownii, Prunus armeniaca seed, and Poria cocos. Fritillaria thunbergii is cleaned and crushed, Morus alba root bark is cleaned and shredded, Taraxacum mongolicum is cleaned and cut into sections, Platycodon grandiflorus is cleaned and cut into thick slices, Prunus armeniaca seed is cleaned and crushed, Poria cocos is cleaned and cut into pieces, and Lepidium apetalum seed is stir-fried according to the stir-frying method until it pops. (2) Take the raw medicinal materials from step (1), add water and decoct 2-3 times, combine the decoctions and concentrate to an extract with a relative density of 1.15-1.25 at 50-60℃, add ethanol for precipitation, let stand, take the supernatant, concentrate, and obtain concentrated solution. (3) The concentrate obtained in step (2) is prepared into a clinically acceptable dosage form by adding acceptable excipients or solvents using conventional techniques or methods in the art.

7. The preparation method according to claim 6, characterized in that, In step (2), the ratio of water to the mass of medicinal materials is 6-10:

1.

8. The preparation method according to claim 6, characterized in that, Step (2) involves adding water and simmering for 2-3 hours.

9. The preparation method according to claim 6, characterized in that, In step (2), the alcohol content during the alcohol precipitation process is 60%-80%.

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