Pharmaceutical composition containing pseudo-ginseng extract as well as preparation method and application of pharmaceutical composition

Abstract

The invention discloses a pharmaceutical composition containing a pseudo-ginseng extract as well as a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicines. The invention provides a pharmaceutical composition containing a pseudo-ginseng extract, and tests prove that the pharmaceutical composition containing the pseudo-ginseng extract has a treatment effect on bacterial pneumonia induced by klebsiella pneumonia. Specifically, the pharmaceutical composition containing the pseudo-ginseng extract can significantly reduce the levels of IL-6, IL-1beta and TNF-alpha in alveolar lavage fluid; the mouse lung index is obviously reduced; the bacterial load in the lung tissue of the mouse is obviously reduced; the mouse lung tissue injury degree is obviously reduced; the number of neutrophils and the number of leukocytes in mouse blood are obviously reduced; the composition also has the effect of remarkably relieving increase of inflammatory factors in serum caused by klebsiella pneumoniae, and the effect is equivalent to or superior to that of a positive control drug ceftriaxone sodium. The invention provides a new choice and idea for clinical treatment of bacterial pneumonia.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a pharmaceutical composition containing Panax notoginseng extract, its preparation method, and its application. Background Technology

[0002] Pneumonia is usually caused by viral or bacterial infections, and occasionally by other microorganisms. Klebsiella pneumoniae is the leading opportunistic pathogen causing community-acquired pneumonia. Klebsiella pneumoniae can induce various diseases, including pneumonia, urinary tract infections, sepsis, and septicemia, with pneumonia being the most common. Due to the high variability and drug resistance of Klebsiella pneumoniae, the number of drugs available for treating Klebsiella pneumoniae infections is decreasing, seriously affecting human quality of life and health. Patients with Klebsiella pneumoniae pneumonia are highly susceptible to developing lung abscesses, cavitation, and empyema, with a mortality rate as high as 50%. When the disease progresses to sepsis, the mortality rate approaches 100%. Acute lung injury is a consequence of pneumonia, caused by damage to alveolar epithelial cells and capillary endothelial cells due to various direct or indirect factors, resulting in diffuse interstitial and alveolar edema, leading to acute hypoxic respiratory failure. The main treatment for bacterial pneumonia is respiratory support therapy, such as oxygen therapy, non-invasive mechanical ventilation, and invasive ventilation, to improve hypoxemia. Treatment for bacterial pneumonia differs from respiratory support therapy for acute lung injury. Currently, treatment primarily involves antibiotics such as penicillin, erythromycin, gentamicin, and ofloxacin. Immunotherapy, including immunoglobulins, transfer factor, and thymosin, is also used as adjunctive therapy. However, long-term use of antibiotics can easily lead to drug resistance and side effects, and immunotherapy is still in the experimental stage. Therefore, exploring new methods for treating bacterial pneumonia is of great significance.

[0003] Traditional Chinese medicine (TCM) believes that bacterial pneumonia is mostly caused by external wind-heat and phlegm-heat. The lungs govern respiration and regulate water metabolism, acting as the upper source of water. They thrive on a clean and descending nature, preferring upward movement. When external pathogens invade, the lungs lose their normal descending function, and their cleansing and descending functions fail, causing lung qi to flow in reverse. The impaired transformation and transportation of fluids leads to stagnation in the lung channels, forming phlegm. Alternatively, heat-related pathogens may directly damage lung fluids, condensing them into phlegm. The combination of phlegm and heat obstructs the airways, causing lung qi stagnation. Lung qi stagnation further impairs blood circulation, disrupts liver function, and deprives the heart of nourishment, resulting in insufficient heart qi. The phlegm-heat becomes intense and persistent, eventually transforming into fire, with phlegm and fire mutually aggravating each other, invading the heart and liver. Therefore, utilizing TCM to treat bacterial pneumonia is an urgent issue that needs to be emphasized and addressed in the clinical management of pneumonia. Summary of the Invention

[0004] The purpose of this invention is to provide a pharmaceutical composition containing Panax notoginseng extract, its preparation method, and its application, to solve the problems existing in the prior art. Experiments have confirmed that the pharmaceutical composition containing Panax notoginseng extract has a therapeutic effect on bacterial pneumonia induced by Klebsiella pneumoniae. This invention provides a new option and approach for the clinical treatment of bacterial pneumonia.

[0005] To achieve the above objectives, the present invention provides the following solution: The present invention provides a pharmaceutical composition containing Panax notoginseng extract, which is composed of the following raw materials in parts by weight: 8-12 parts of Panax notoginseng extract, 4-6 parts of Sophora flavescens root and 4-6 parts of Uncaria rhynchophylla. The Panax notoginseng extract was obtained by enzymatic hydrolysis and extraction.

[0006] Optionally, the ingredients are composed of the following parts by weight: 10 parts Panax notoginseng extract, 5 parts Sophora flavescens root, and 5 parts Uncaria rhynchophylla.

[0007] The present invention also provides a method for preparing the pharmaceutical composition containing Panax notoginseng extract, comprising the following steps: After pulverizing Panax notoginseng, trypsin was added for enzymatic hydrolysis. After the enzymatic hydrolysis was completed, the enzyme was inactivated, filtered, and the filtrate was extracted and concentrated under reduced pressure to obtain Panax notoginseng extract. The powdered Sophora flavescens and Uncaria rhynchophylla were mixed together, soaked in water, heated and extracted, filtered, and the first filtrate and residue were collected; water was added to the residue, heated and extracted again, filtered, and the second filtrate was collected; the first and second filtrates were combined and concentrated under reduced pressure to obtain a thick paste, thus obtaining the Chinese herbal extract. The pharmaceutical composition containing Panax notoginseng extract is obtained by mixing the Panax notoginseng extract and the traditional Chinese medicine extract evenly.

[0008] Optionally, the amount of trypsin added is 0.7%-1% of the mass of the pulverized Panax notoginseng; The enzymatic hydrolysis time is 20 min-30 min; The extraction conditions were as follows: extraction was performed sequentially using ethyl acetate and tert-butanol, and the tert-butanol phase was collected.

[0009] Optionally, the weight ratio of the mixture to water is 1:(7-8), the soaking time is 1-1.5 hours, and the heating extraction time is 1-1.5 hours; The mass ratio of the filter residue to water is 1:(5-6), and the reheating extraction time is 1-1.25 hours.

[0010] Optionally, the weight ratio of the mixture to water is 1:8, the soaking time is 1 hour, and the heating extraction time is 1.5 hours; The mass ratio of the filter residue to water is 1:6, and the reheating extraction time is 1 hour.

[0011] The present invention also provides the use of the pharmaceutical composition containing Panax notoginseng extract in the preparation of a medicament for treating bacterial pneumonia.

[0012] Optionally, the bacterial pneumonia is bacterial pneumonia induced by Klebsiella pneumoniae.

[0013] The present invention also provides a medicament for treating bacterial pneumonia, the medicament comprising the aforementioned pharmaceutical composition containing Panax notoginseng extract.

[0014] Optionally, the bacterial pneumonia is bacterial pneumonia induced by Klebsiella pneumoniae.

[0015] The present invention discloses the following technical effects: This invention provides a pharmaceutical composition containing Panax notoginseng extract. Experiments have confirmed that this composition has a therapeutic effect on bacterial pneumonia induced by Klebsiella pneumoniae. Specifically, the composition significantly reduces the levels of IL-6, IL-1β, and TNF-α in bronchoalveolar lavage fluid; significantly reduces the lung index in mice; significantly reduces the bacterial load in mouse lung tissue; significantly alleviates the degree of lung tissue damage in mice; significantly reduces the number of neutrophils and white blood cells in mouse blood; and also significantly alleviates the increase in serum inflammatory factors caused by Klebsiella pneumoniae. These effects are comparable to or superior to those of the positive control drug ceftriaxone sodium. This invention provides a new option and approach for the clinical treatment of bacterial pneumonia. Detailed Implementation

[0016] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0017] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0018] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0019] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0020] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0021] In the prior art, a patent application for treating bacterial pneumonia using a traditional Chinese medicine composition includes: CN119280347A - A traditional Chinese medicine composition used in the preparation of a drug for treating or preventing bacterial pneumonia, wherein the composition comprises: 1-3 parts honey-processed ephedra, 1-10 parts bitter almond, 1-6 parts platycodon, 1-6 parts angelica, 1-6 parts fritillaria thunbergii, 1-6 parts stemona, 1-3 parts oroxylum indicum, 1-10 parts glehnia littoralis, and 1-3 parts licorice. Experimental verification shows that this composition can significantly reduce the white blood cell count and neutrophil count in rats with lipopolysaccharide-induced bacterial pneumonia, and increase the percentage of lymphocytes and platelets, thus inhibiting the body's inflammatory response, clearing antigens, and promoting recovery; it can also significantly reduce the lung index in rats with lipopolysaccharide-induced bacterial pneumonia, thus inhibiting pulmonary inflammatory lesions and clearing stagnation and swelling. However, it is designed for rats with lipopolysaccharide-induced bacterial pneumonia. Those skilled in the art do not know whether the herbal composition is effective against pneumonia induced by Klebsiella pneumoniae. Furthermore, the herbal composition contains a large number of drugs and has a slightly complex composition, which poses challenges in quality control.

[0022] CN120678839A - A composition, preparation method, and application for combating bacterial pneumonia. This paper provides a composition obtained by fermenting a traditional Chinese medicine composition using compound probiotics. The raw materials of the traditional Chinese medicine composition are 10-25 parts loquat leaf, 5-15 parts monk fruit, 5-15 parts licorice root, 2-10 parts tangerine peel, and 1-8 parts malva nut. The compound probiotics are *Lactobacillus plantarum* HCS03-001, *Lactobacillus reuteri* HCS02-001, and *Lactobacillus rhamnosus* HCS01-013 in a mass ratio of 1-2:1:1. It utilizes extracts from medicinal and edible raw materials as a culture medium for fermentation, combining the post-biotics produced by specific lactic acid bacteria to generate substances beneficial to the throat and lungs, thus combining the effects of probiotics and medicinal and edible raw materials. Using this specific traditional Chinese medicine composition, its anti-pneumonia effect after fermentation is significantly superior to other large-scale prescriptions. A fermentation broth prepared using a specific ratio of *Lactobacillus plantarum* HCS03-001, *Lactobacillus reuteri* HCS02-001, and *Lactobacillus rhamnosus* HCS01-013 showed significantly superior efficacy compared to other probiotic strains. The efficacy of the composition was validated using a zebrafish bacterial pneumonia model established with LPS. The study found that during LPS-induced acute lung injury, inflammatory cells such as neutrophils were recruited and activated. After activation, these inflammatory cells infiltrated lung tissue and released inflammatory mediators, leading to an increase in neutrophils and macrophages in zebrafish, and a rise in the relative expression levels of tgfb1a, il1b, and tnfa genes. The composition exhibited antibacterial pneumonia efficacy, specifically by downregulating the relative expression level of the tgfβ-1 gene. However, it is also targeted at bacterial pneumonia caused by LPS. Those skilled in the art do not know whether its composition is effective against pneumonia induced by Klebsiella pneumoniae. Furthermore, its active ingredient is a fermentation product of a fermented medicinal and edible raw material extract of lactic acid bacteria in a specific ratio and with a specific strain. It is not an antibacterial pneumonia effect achieved solely by traditional Chinese medicine or its extracts.

[0023] Northern Bean Root is bitter and cold in nature. It enters the lung, stomach, and large intestine meridians and can clear heat and detoxify, dispel wind and relieve pain.

[0024] Uncaria rhynchophylla is cold in nature and sweet in taste, entering the liver and pericardium meridians. It can relieve wind and stop spasms, clear liver heat, and calm liver yang.

[0025] Example 1: A pharmaceutical composition containing Panax notoginseng extract and its preparation method The pharmaceutical composition containing Panax notoginseng extract is composed of the following raw materials in parts by weight: 10 parts Panax notoginseng extract, 5 parts Sophora flavescens root, and 5 parts Uncaria rhynchophylla.

[0026] The preparation method includes the following steps: Preparation of Panax notoginseng extract: Panax notoginseng was washed, dried, and pulverized to 50 mesh to obtain Panax notoginseng powder. The Panax notoginseng powder was added to 4 times the amount of deionized water, and then 0.7% of the mass of Panax notoginseng powder was added to trypsin for 30 min. After enzymatic hydrolysis, the temperature was raised to 95℃ to inactivate the enzyme, cooled to room temperature, filtered, and the filtrate was collected. The obtained filtrate was then extracted sequentially with ethyl acetate and tert-butanol, and the tert-butanol phase was collected. The solvent was removed by concentration under reduced pressure to obtain Panax notoginseng extract.

[0027] Preparation of Chinese herbal extracts: Weigh out parts by weight of Sophora flavescens and Uncaria rhynchophylla, wash and dry them, and then pulverize them into coarse powder; Mix the pulverized raw materials evenly, add water equal to 8 times the total weight of the raw materials, soak for 1 hour, heat to boiling, maintain a gentle boil for 1.5 hours, filter, and collect the first filtrate and residue. Add water equal to 6 times the total weight of the raw materials to the filter residue, heat to boiling, maintain a gentle boil for 1 hour, filter, and collect the second filtrate; The two filtrates were combined and concentrated under reduced pressure to a thick paste with a relative density of 1.05 (60℃) to obtain the Chinese herbal extract.

[0028] Preparation of a pharmaceutical composition containing Panax notoginseng extract: Panax notoginseng extract and traditional Chinese medicine extract are mixed evenly to obtain a pharmaceutical composition containing Panax notoginseng extract.

[0029] Example 2: A pharmaceutical composition containing Panax notoginseng extract and its preparation method The pharmaceutical composition containing Panax notoginseng extract is composed of the following raw materials in parts by weight: 8 parts Panax notoginseng extract, 4 parts Sophora flavescens root, and 6 parts Uncaria rhynchophylla.

[0030] The preparation method includes the following steps: Preparation of Panax notoginseng extract: Panax notoginseng was washed, dried, and pulverized to 50 mesh to obtain Panax notoginseng powder. The Panax notoginseng powder was added to 3 times the amount of deionized water, and then 1.0% of the mass of Panax notoginseng powder was added to trypsin for 20 min. After enzymatic hydrolysis, the temperature was raised to 95℃ to inactivate the enzyme, cooled to room temperature, filtered, and the filtrate was collected. The obtained filtrate was then extracted sequentially with ethyl acetate and tert-butanol, and the tert-butanol phase was collected. The solvent was removed by concentration under reduced pressure to obtain Panax notoginseng extract.

[0031] Preparation of Chinese herbal extracts: Weigh out parts by weight of Sophora flavescens and Uncaria rhynchophylla, wash and dry them, and then pulverize them into coarse powder; Mix the pulverized raw materials evenly, add water at 7 times the total weight of the raw materials, soak for 1.5 hours, heat to boiling, maintain a gentle boil for 1.25 hours, filter, and collect the first filtrate and residue. Add water equal to 5 times the total weight of the raw materials to the filter residue, heat to boiling, maintain a gentle boil for 1.25 hours, filter, and collect the second filtrate; The two filtrates were combined and concentrated under reduced pressure to a thick paste with a relative density of 1.08 (60℃) to obtain the Chinese herbal extract.

[0032] Preparation of a pharmaceutical composition containing Panax notoginseng extract: Panax notoginseng extract and traditional Chinese medicine extract are mixed evenly to obtain a pharmaceutical composition containing Panax notoginseng extract.

[0033] Example 3 A pharmaceutical composition containing Panax notoginseng extract and its preparation method The pharmaceutical composition containing Panax notoginseng extract is composed of the following raw materials in parts by weight: 12 parts Panax notoginseng extract, 6 parts Sophora flavescens root, and 4 parts Uncaria rhynchophylla.

[0034] The preparation method includes the following steps: Preparation of Panax notoginseng extract: Panax notoginseng was washed, dried, and pulverized to 50 mesh to obtain Panax notoginseng powder. The Panax notoginseng powder was added to 5 times the amount of deionized water, and then 0.9% of the mass of Panax notoginseng powder was added to trypsin for 25 min of enzymatic hydrolysis. After the enzymatic hydrolysis was completed, the temperature was raised to 95℃ to inactivate the enzyme, cooled to room temperature, filtered, and the filtrate was collected. The obtained filtrate was then extracted sequentially with ethyl acetate and tert-butanol, and the tert-butanol phase was collected. The solvent was removed by concentration under reduced pressure to obtain Panax notoginseng extract.

[0035] Preparation of Chinese herbal extracts: Weigh out parts by weight of Sophora flavescens and Uncaria rhynchophylla, wash and dry them, and then pulverize them into coarse powder; Mix the pulverized raw materials evenly, add water equal to 8 times the total weight of the raw materials, soak for 1.25 hours, heat to boiling, maintain a gentle boil for 1 hour, filter, and collect the first filtrate and residue. Add water equal to 6 times the total weight of the raw materials to the filter residue, heat to boiling, maintain a gentle boil for 1 hour, filter, and collect the second filtrate; The two filtrates were combined and concentrated under reduced pressure to a thick paste with a relative density of 1.07 (60℃) to obtain the Chinese herbal extract.

[0036] Preparation of a pharmaceutical composition containing Panax notoginseng extract: Panax notoginseng extract and traditional Chinese medicine extract are mixed evenly to obtain a pharmaceutical composition containing Panax notoginseng extract.

[0037] Comparative Example 1 Same as Example 1, except that it contains only 20 parts of Panax notoginseng extract.

[0038] Comparative Example 2 Same as Example 1, except that it contains only 10 parts of Sophora flavescens and 10 parts of Uncaria rhynchophylla.

[0039] Application example: The use of pharmaceutical compositions containing Panax notoginseng extract in the treatment of bacterial pneumonia. 1. Laboratory animals, main drugs and reagents 160 healthy BALB / c mice, SPF grade, weighing 20±2g.

[0040] Klebsiella pneumoniae (KP) was purchased from the China Industrial Microbial Culture Collection Center, strain number CICC10870. Ceftriaxone sodium (CRO) was purchased from Ruiyang Pharmaceutical Co., Ltd., and ELISA kits for IL-6, IL-4, IL-1β, and TNF-α were purchased from Wuhan Yipu Biotechnology Co., Ltd.

[0041] 2. Animal modeling and drug administration Healthy BALB / c mice were acclimatized for 3 days in a laboratory at 25±5℃ and 40-70% relative humidity. They were fed standard feed and had free access to water. Before modeling, mice were weighed and randomly divided into a blank control group and a model group (KP, 1.04×10⁻⁶). 9 The groups included: KP + 2.5 mg / kg of the pharmaceutical composition containing Panax notoginseng extract prepared in Example 1, KP + 5 mg / kg of the pharmaceutical composition containing Panax notoginseng extract prepared in Example 2, KP + 200 mg / kg of the pharmaceutical composition containing Panax notoginseng extract prepared in Example 3, Comparative Example 1 (KP + Panax notoginseng extract prepared in Comparative Example 1), Comparative Example 2 (KP + traditional Chinese medicine extract prepared in Comparative Example 2), and positive control group (KP + CRO 200 mg / kg), with 20 animals in each group.

[0042] Based on a KP concentration of 1.04 × 10⁻⁶ 9 A mouse model of bacterial pneumonia was established by intraperitoneal instillation of 0.12 mL / 10g of 0.4% sodium barbital. Before modeling, mice in each group were anesthetized by intraperitoneal injection of 0.4% sodium barbital. The mice were placed in a supine position on the operating table, and their mouths were opened using a mouth gag. A quantitative nebulizer was used to inject 50 μL of KP solution (the blank control group received an equal volume of sterile saline) into the lungs through the epiglottic cartilage opening. Once the model was established, the mice were given water and feed after recovery. Examples 1-3, as well as Comparative Examples 1 and 2, received intravenous injections of the corresponding drugs (diluted with 1 mL of saline in each group) at 0 h, 3 h, 24 h, 48 h, and 72 h after modeling. The CRO group received intraperitoneal administration of 200 mg / kg at 0 h, and the KP model group received an equal volume of saline via intravenous injection.

[0043] 3. Detection indicators 3.1 Determination of Bronchoalveolar Lavage Fluid (BALF) Extraction Ten mice in each group were sacrificed 72 h after modeling. The thoracic cavity of the mice was opened, the right lung was ligated and tracheal intubation was performed. 0.3 mL of PBS solution was drawn into the trachea with a 1 mL syringe and injected into the trachea. The lavage was repeated 3 times. The above operation was repeated 3 times. The lavage fluid was combined and centrifuged at 4℃ and 1600 rpm / min for 10 min. The supernatant was collected and the levels of IL-6, IL-1β and TNF-α were detected according to the kit instructions.

[0044] 3.2 Lung tissue index measurement Ten mice in each group were sacrificed 72 hours after modeling and their lungs were removed.

[0045] Lung index detection: Lung tissues of mice in each group were collected and the total lung weight was measured. The lung index of each group of mice was calculated according to the formula: Lung index (%) = Lung wet weight (g) / Body weight (g) × 100.

[0046] Lung bacterial load assay: Approximately 8 mg of lung tissue was homogenized in physiological saline, centrifuged, and 2-3 mL was transferred to a cuvette. The OD value was then measured. 600 The bacterial load in the lung tissue of mice in each group was assessed.

[0047] 3.3 Serum marker determination Before the mice were sacrificed, blood was collected from their eyeballs and routine blood tests were performed using a blood routine instrument to detect routine indicators such as white blood cells and neutrophils in the mice's blood.

[0048] After the complete blood count was performed, the remaining blood was allowed to coagulate naturally at room temperature for 30 min, then centrifuged at 3000 r / min for 20 min at 4℃ to separate the serum. The serum was then aliquoted and frozen at -80℃, and the levels of IL-4 and TNF-α inflammatory factors in the serum were detected according to the kit instructions.

[0049] 4. Experimental Results 4.1 Effects of pharmaceutical compositions containing Panax notoginseng extract on the levels of IL-6, IL-1β, and TNF-α in BALF The results are shown in Table 1. Compared with the blank control group, the levels of IL-6, IL-1β and TNF-α in the BALF of the model group mice were significantly increased. Compared with the model group, the levels of IL-6, IL-1β and TNF-α in the BALF of the positive control group mice were significantly decreased. The levels of IL-6, IL-1β and TNF-α in the BALF of the Example 1-3 groups were significantly decreased, which was comparable to the positive control group and significantly better than the Comparative Example 1-2 groups.

[0050] The results showed that Klebsiella pneumoniae could cause an increase in the levels of IL-6, IL-1β and TNF-α in the BALF of BALB / c mice, while the drug composition containing Panax notoginseng extract had the effect of reducing the increase in the levels of IL-6, IL-1β and TNF-α in BALF caused by Klebsiella pneumoniae.

[0051] Table 1. Effects of pharmaceutical compositions containing Panax notoginseng extract on the levels of IL-6, IL-1β, and TNF-α in BALF (pg / mL) Note: This indicates that compared to the model group, p < 0.05. # indicates that p < 0.001 compared to the model group, and ## indicates that p < 0.01 compared to Comparative Example 1. The same applies to the following tables.

[0052] 4.2 Effects of pharmaceutical compositions containing Panax notoginseng extract on the degree of lung tissue damage (1) Effect on lung index: Compared with the blank group (0.49%), the lung index of the model group mice (1.30%) was significantly increased (P<0.05), indicating that bacterial infection caused pathological damage to the lungs and the pneumonia mouse model was successfully established. Compared with the model group, the intervention of the Example 1-3 groups and the positive control group (0.70%, 0.74%, 0.77% and 0.69%) significantly reduced the lung index of mice, and was significantly better than the control groups 1-2 (1.00% and 1.05%).

[0053] (2) Effect on bacterial load: Compared with the control group (0×10 7 Compared to the model group (4.31 × 10⁻⁶ CFU / mL), the CFU / mL concentration was significantly lower. 7 The bacterial load in the lung tissue of mice with CFU / mL was significantly increased. Compared with the model group, the bacterial load in groups 1-3 and the positive control group (3.11×10⁻³ CFU / mL) was significantly increased. 7 CFU / mL, 3.23×10 7 CFU / mL, 3.29×10 7 CFU / mL and 3.38×10 7 Intervention with CFU / mL significantly reduced bacterial load in mouse lung tissue, and was significantly better than control groups 1-2 (3.89×10⁻⁶). 7 CFU / mL and 3.90×10 7 (CFU / mL).

[0054] 4.3 Effects of pharmaceutical compositions containing Panax notoginseng extract on blood neutrophil and white blood cell counts Table 2 shows that, compared with the blank control group, the number of neutrophils (NEUT) and white blood cells (WBC) in the blood of mice in the model group were significantly increased; compared with the model group, the positive control group could reduce the number of NEUT in the blood, but had no significant effect on WBC. The number of NEUT and WBC in the blood of mice in Examples 1-3 were all significantly reduced. The number of NEUT and WBC in the blood of mice in Comparative Examples 1-2 was increased compared with the model control group, but the difference was not significant.

[0055] The results showed that Klebsiella pneumoniae could cause elevated levels of NEUT and WBC in the blood of BALB / c mice, while the drug composition containing Panax notoginseng extract had the effect of reducing the elevated levels of neutrophils and white blood cells caused by Klebsiella pneumoniae, and the effect was better than that of the positive control drug CRO.

[0056] Table 2. Effects of pharmaceutical compositions containing Panax notoginseng extract on blood NEUT and WBC (10 9 / L) 4.4 Effects of pharmaceutical compositions containing Panax notoginseng extract on serum IL-6 and TNF-α levels The levels of IL-6 and TNF-α in mouse ocular blood were detected using an ELISA kit. The results are shown in Table 3. Compared with the blank control group, the serum IL-6 and TNF-α levels of the model group mice were significantly increased. Compared with the model group, the positive control group significantly reduced the serum IL-6 and TNF-α levels of mice. The groups in Examples 1-3 significantly reduced the serum IL-6 and TNF-α levels of mice, and the effects of the groups in Examples 1-3 were significantly better than those in the comparative groups 1-2.

[0057] The results showed that Klebsiella pneumoniae could cause an increase in serum inflammatory factors IL-6 and TNF-α levels in BALB / c mice, while the drug composition containing Panax notoginseng extract could reduce the increase in inflammatory factors caused by Klebsiella pneumoniae, and its inhibitory effect was comparable to that of the positive control drug.

[0058] Table 3. Effects of pharmaceutical compositions containing Panax notoginseng extract on serum IL-6 and TNF-α levels (pg / mL) Based on the above experimental results, the pharmaceutical composition containing Panax notoginseng extract has a therapeutic effect on bacterial pneumonia induced by Klebsiella pneumoniae. Specifically, the pharmaceutical composition containing Panax notoginseng extract can significantly reduce the levels of IL-6, IL-1β, and TNF-α in bronchoalveolar lavage fluid; significantly reduce the lung index in mice; significantly reduce the bacterial load in mouse lung tissue; significantly alleviate the degree of lung tissue damage in mice; significantly reduce the number of neutrophils and white blood cells in mouse blood; and also significantly alleviate the increase in serum inflammatory factors caused by Klebsiella pneumoniae. These effects are comparable to or better than those of the positive control drug ceftriaxone sodium. In conclusion, this invention provides a pharmaceutical composition containing Panax notoginseng extract, which has been experimentally verified to have a therapeutic effect on bacterial pneumonia induced by Klebsiella pneumoniae. This invention provides a new option and approach for the clinical treatment of bacterial pneumonia.

[0059] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A pharmaceutical composition comprising an extract of Panax notoginseng, characterized in that, The drug composition containing the notoginseng extract is prepared from the following raw materials in parts by weight: notoginseng extract 8-12 parts, north radix sophorae flavescentis 4-6 parts, and uncaria 4-6 parts. The notoginseng extract is obtained by enzymatic hydrolysis of notoginseng.

2. The pharmaceutical composition containing the extract of Panax notoginseng according to claim 1, wherein the extract of Panax notoginseng is prepared by extracting Panax notoginseng with water, and then extracting the residue with 50% ethanol. The drug composition containing the notoginseng extract is prepared from the following raw materials in parts by weight: notoginseng extract 8-12 parts, north radix sophorae flavescentis 4-6 parts, and uncaria 4-6 parts.

3. The method for preparing the pharmaceutical composition containing Panax notoginseng extract as described in claim 1 or 2, characterized in that, The method comprises the following steps: The notoginseng is crushed and then enzymatically hydrolyzed by adding trypsin, and the enzyme is inactivated after the enzymatic hydrolysis is completed, and then filtered, and the filtrate is extracted and concentrated under reduced pressure to obtain the notoginseng extract; The north radix sophorae flavescentis and uncaria are crushed and mixed to obtain a mixture, and then soaked in water and heated to extract, filtered, and the first filtrate and filter residue are collected; water is added to the filter residue, and then heated again to extract, filtered, and the second filtrate is collected; the first filtrate and the second filtrate are combined, and concentrated under reduced pressure to obtain a thick paste, thereby obtaining the traditional Chinese medicine extract; The notoginseng extract and the traditional Chinese medicine extract are uniformly mixed to obtain the drug composition containing the notoginseng extract.

4. The production method according to claim 3, wherein The trypsin is added in an amount of 0.7%-1% of the mass of the crushed notoginseng; The enzymatic hydrolysis is performed for 20-30 min; The extraction is performed by sequentially using ethyl acetate and tert-butyl alcohol for extraction, and collecting the tert-butyl alcohol phase.

5. The production method according to claim 3, wherein The weight ratio of the mixture to water is 1: (7-8), the soaking time is 1-1.5 hours, and the heating extraction time is 1-1.5 hours; The mass ratio of the filter residue to water is 1: (5-6), and the heating extraction time is 1-1.25 hours.

6. The production method according to claim 5, wherein The weight ratio of the mixture to water is 1:8, the soaking time is 1 hour, and the heating extraction time is 1.5 hours; The mass ratio of the filter residue to water is 1:6, and the heating extraction time is 1 hour.

7. Use of the drug composition containing the notoginseng extract according to claim 1 or 2 in the preparation of a drug for treating bacterial pneumonia.

8. Use according to claim 7, wherein the compound is ###0002### The bacterial pneumonia is Klebsiella pneumoniae-induced bacterial pneumonia.

9. A medicament for treating bacterial pneumonia, characterized by comprising a compound of the formula (I) as an active ingredient. The drug comprises the drug composition containing the notoginseng extract according to claim 1 or 2.

10. The medicament according to claim 9, wherein The bacterial pneumonia is Klebsiella pneumoniae-induced bacterial pneumonia.

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