A pharmaceutical composition for treating oviduct inflammation and peritonitis of laying hens and a preparation method thereof

Abstract

The application provides a pharmaceutical composition for treating oviduct inflammation and peritonitis of laying hens and a preparation method thereof, and belongs to the technical field of veterinary drugs. The pharmaceutical composition is obtained by mixing 2-10 parts of artemisinic acid, 1-10 parts of marrubiin hydrochloride, 1-10 parts of sodium salicylate, 0.001-0.005 parts of imipenem / cilastatin sodium and auxiliary materials. The pharmaceutical composition can treat oviduct inflammation, peritonitis and intestinal secondary infection of laying hens through anti-pathogenic microorganism infection and anti-inflammatory pathways, and significantly improves the production performance of laying hens. After the chickens are medicated, the effect is fast, the egg production rate is obviously increased, and the substandard egg rate is obviously decreased. The oviduct inflammation and peritonitis of laying hens over 300 days old can be effectively solved, the clinical use is safe and reliable, the meat and egg food quality and safety can be improved, and it is particularly important for large-scale laying hen farms.

Description

Technical Field

[0001] This invention relates to the field of veterinary medicine technology, and in particular to a pharmaceutical composition for treating oviductitis and peritonitis in laying hens and its preparation method. Background Technology

[0002] In recent years, oviductitis and peritonitis have become common in caged laying hens. Infections with bacteria such as E. coli, Salmonella, and Pasteurella are significant causes of oviductitis / peritoneitis in laying hens, especially during the initial laying period and peak egg production. Oviductitis in laying hens often leads to secondary diarrhea, and clinically is characterized by inflammation of the ovary, oviduct, and peritoneum. Affected hens mainly exhibit pain and restlessness, standing motionless, drooping wings, and ruffled feathers. Some may lie on their abdomen or become lethargic. Eggs often have bloodstains on their shells, and purulent discharge frequently flows from the oviduct, contaminating the feathers around the vent and below. Laying becomes difficult, and the hens are prone to laying soft-shelled, thin-shelled, deformed, sandy-shelled, small, and white-shelled eggs, making it a prevalent disease threatening the healthy development of the poultry industry. Due to the diverse and widespread presence of pathogens, infections often become complex, with an increase in mixed infections of different bacteria, viruses, and parasites, and a rise in secondary infections. While conventional methods and simple drug treatments, such as antibiotics or chemical therapy, can improve the production performance, egg production rate, and feed conversion ratio of laying hens to some extent, they can easily lead to drug resistance in pathogenic strains, and drug residues can also endanger human health.

[0003] Furthermore, even after a disease is diagnosed, issues with drug combinations, formulations, and drug resistance cause inconvenience for farmers, making it difficult to control the disease effectively. During treatment, factors such as drug insensitivity, dehydration due to mid-treatment changes, and prolonged treatment can severely weaken the hens' resistance, leading to secondary infections and ultimately reducing their egg production performance after recovery, significantly impacting egg production rates and farming profits.

[0004] Currently, the development and market launch of new drugs for this disease are slow, and conventional treatments also face a serious problem of drug resistance. Traditional Chinese veterinary medicines and prescriptions can effectively prevent and treat animal diseases, and can also reduce antibiotic use and delay or even eliminate the emergence of drug-resistant strains. However, they have shortcomings such as simple and crude preparation processes, resulting in ineffective release of active ingredients. Furthermore, due to the short digestive tract of chickens, the bioavailability of powdered drugs is low, and their palatability and absorption are poor, often requiring increased dosages, further leading to low drug utilization and resource waste. Large-scale integrated egg-laying hen farms use methods such as drinking water, spraying, and mixing with feed for group medication. Powdered drugs are only suitable for mixing with feed, limiting their use and promotion. In addition, traditional Chinese medicine prescriptions contain a large number of ineffective ingredients, which may interact with each other, leading to reduced efficacy and drug residues. Related studies report that commonly used veterinary clinical drugs such as Sihuang Zhili Granules, Baitouweng Oral Liquid, and Bailong Granules are not very effective in treating oviductitis in laying hens, and the condition is prone to recurrence. The use of warming and tonifying Chinese herbal powders such as Jidan San and Yimu Zengdan San also suffers from low cure rates, slow onset of action, and low cost-effectiveness. Given the shortcomings of traditional Chinese medicine formulas, such as high levels of impurities in the raw materials, poor absorption, slow release of active ingredients, poor efficacy in acute cases, and inability to target the specific symptoms, there is an urgent market need for a highly effective and low-toxicity treatment for oviductitis and peritonitis in laying hens. Summary of the Invention

[0005] The purpose of this invention is to provide a pharmaceutical composition for treating oviductitis and peritonitis in laying hens.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0007] This invention provides a pharmaceutical composition for treating oviductitis and peritonitis in laying hens.

[0008] Preferably, the pharmaceutical composition comprises the following raw materials in parts by weight: 2-10 parts artemisinic acid, 1-10 parts leonurine hydrochloride, 1-10 parts sodium salicylate, and 0.001-0.005 parts imipenem / cilastatin sodium.

[0009] Preferably, the pharmaceutical composition further comprises the following excipients in parts by weight: 5-10 parts sodium chloride, 10-30 parts sodium bicarbonate, and 1-3 parts sodium bisulfite.

[0010] Preferably, the pharmaceutical composition is an oral or injectable formulation.

[0011] Preferably, each 100 mL of the oral or injectable preparation comprises the following ingredients by weight: 2-10 g artemisinic acid, 1-10 g leonurine hydrochloride, 1-10 g sodium salicylate, 0.001-0.005 g imipenem / cilastatin sodium, 5-10 g sodium chloride, 10-30 g sodium bicarbonate, and 1-3 g sodium bisulfite.

[0012] The present invention also provides a method for preparing a pharmaceutical composition for treating oviductitis and peritonitis in laying hens, characterized by comprising the following steps: adding artemisinic acid, imipenem / cilastatin sodium, leonurine hydrochloride, sodium salicylate, sodium chloride, sodium bicarbonate, and sodium bisulfite to water for injection, adjusting the pH to 6.5-7.0, then adding water for injection to make up the volume, filtering for sterilization, and packaging.

[0013] Preferably, the filtration sterilization is performed by using a sterile membrane filter with a pore size of 0.2 to 0.25 μm.

[0014] The pharmaceutical composition prepared by this invention has good antibacterial effects, can reduce bacterial drug resistance, and exhibits synergistic antibacterial effects compared to using drugs alone. It can also inhibit the increase of capillary permeability and has a significant anti-inflammatory effect on acute exudative inflammation. Furthermore, it has extremely low toxicity and a high clinically safe dosage.

[0015] The pharmaceutical composition prepared in this invention can treat oviduct inflammation, peritonitis, and secondary intestinal infections in laying hens through antimicrobial infection and anti-inflammatory mechanisms, significantly improving the laying performance of hens. After administration, the medication is rapidly effective, significantly increasing egg production and reducing the rate of substandard eggs. It can effectively address common oviduct inflammation and peritonitis in laying hens over 300 days old, is safe and reliable for clinical use, and can improve the quality and safety of poultry and egg products, making it particularly important for large-scale laying hen farms. Detailed Implementation

[0016] This invention provides a pharmaceutical composition for treating oviductitis and peritonitis in laying hens. The pharmaceutical composition comprises the following raw materials in parts by weight: 2-10 parts artemisinic acid, 1-10 parts leonurine hydrochloride, 1-10 parts sodium salicylate, and 0.001-0.005 parts imipenem / cilastatin sodium. Preferably, the pharmaceutical composition comprises the following raw materials in parts by weight: 6 parts artemisinic acid, 5 parts leonurine hydrochloride, 5 parts sodium salicylate, and 0.003 parts imipenem / cilastatin sodium.

[0017] In this invention, the artemisinic acid (Lot#C15H22O2, ≥98%, purchased from Guangdong Wengjiang Chemical Reagent Co., Ltd.); leonurine hydrochloride (Lot#Y202-5, ≥98%, purchased from Chengdu Ruifensi Biotechnology Co., Ltd.); sodium salicylate (Lot#S104177, purity 99.5%, purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.); and imipenem / cilastatin sodium (Imipenem and cilastatin Sodium, ICS, Lot#C51257, purity USP, purchased from Shanghai Mairui Biochemical Technology Co., Ltd.) are used.

[0018] In this invention, the pharmaceutical composition further comprises the following excipients in parts by weight: 5-10 parts sodium chloride, 10-30 parts sodium bicarbonate, and 1-3 parts sodium bisulfite. Preferably, the pharmaceutical composition further comprises the following excipients in parts by weight: 8 parts sodium chloride, 20 parts sodium bicarbonate, and 2 parts sodium bisulfite.

[0019] In this invention, the pharmaceutical composition is an oral or injectable preparation.

[0020] In this invention, each 100 mL of the oral or injectable preparation comprises the following ingredients by weight: 2-10 g artemisinic acid, 1-10 g leonurine hydrochloride, 1-10 g sodium salicylate, 0.001-0.005 g imipenem / cilastatin sodium, 5-10 g sodium chloride, 10-30 g sodium bicarbonate, and 1-3 g sodium bisulfite. Preferably, each 100 mL of the oral or injectable preparation comprises the following ingredients by weight: 5 g artemisinic acid, 8 g leonurine hydrochloride, 5 g sodium salicylate, 0.0025 g imipenem / cilastatin sodium, 9 g sodium chloride, 20 g sodium bicarbonate, and 2 g sodium bisulfite.

[0021] The present invention also provides a method for preparing a pharmaceutical composition for treating oviductitis and peritonitis in laying hens, characterized by comprising the following steps: adding artemisinic acid, imipenem / cilastatin sodium, leonurine hydrochloride, sodium salicylate, sodium chloride, sodium bicarbonate, and sodium bisulfite to water for injection, adjusting the pH to 6.5-7.0, preferably 6.8, then adding water for injection to make up the volume, filtering for sterilization, and packaging.

[0022] In this invention, the filtration sterilization is performed by using a sterile membrane filter with a pore size of 0.2 to 0.25 μm, preferably a sterile membrane filter with a pore size of 0.22 μm.

[0023] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0024] Example 1

[0025] Add 2g of artemisinic acid, 0.001g of imipenem / cilastatin sodium, 10g of leonurine hydrochloride, 5g of sodium salicylate, 10g of sodium chloride, 10g of sodium bicarbonate, and 3g of sodium bisulfite to 60mL of water for injection. Mix well, adjust the pH to 7.0, and then add water for injection to bring the volume to 100mL. Filter the solution through a 0.22μm sterile membrane filter to remove bacteria. Dispense 2mL portions to obtain an oral or injectable formulation of the drug composition for treating oviductitis and peritonitis in laying hens. Store at 4℃ protected from light.

[0026] Example 2

[0027] Using the preparation method described in Example 1, each 100mL oral or injectable dose contains 8g of artemisinic acid, 3g of leonurine hydrochloride, 3g of sodium salicylate, 0.002g of imipenem / cilastatin sodium, 6g of sodium chloride, 25g of sodium bicarbonate, and 2g of sodium bisulfite.

[0028] Example 3

[0029] Using the preparation method described in Example 1, each 100 mL oral or injectable dose contains 10 g of artemisinic acid, 1 g of leonurine hydrochloride, 1 g of sodium salicylate, 0.005 g of imipenem / cilastatin sodium, 5 g of sodium chloride, 30 g of sodium bicarbonate, and 3 g of sodium bisulfite.

[0030] Example 4

[0031] Using the preparation method described in Example 1, each 100 mL oral or injectable dose contains 6 g of artemisinic acid, 7 g of leonurine hydrochloride, 8 g of sodium salicylate, 0.003 g of imipenem / cilastatin sodium, 7 g of sodium chloride, 20 g of sodium bicarbonate, and 1 g of sodium bisulfite.

[0032] Example 5

[0033] Using the preparation method described in Example 1, each 100mL oral or injectable preparation contains 3g of artemisia annua, 5g of leonurine hydrochloride, 10g of sodium salicylate, 0.004g of imipenem / cilastatin sodium, 8g of sodium chloride, 25g of sodium bicarbonate, and 1g of sodium bisulfite.

[0034] Example 6

[0035] Using the preparation method described in Example 1, each 100 mL oral or injectable dose contains 5 g of artemisinic acid, 8 g of leonurine hydrochloride, 5 g of sodium salicylate, 0.0025 g of imipenem / cilastatin sodium, 9 g of sodium chloride, 20 g of sodium bicarbonate, and 2 g of sodium bisulfite.

[0036] Example 7

[0037] Determination of drug MIC (minimum inhibitory concentration), MBC (minimum bactericidal concentration), and combined antimicrobial FICI index.

[0038] (1) Antibacterial Activity Study of Monomeric Active Ingredients, Pharmaceutical Combinations and Antibiotics

[0039] The pharmaceutical combination of Example 6 was selected for the antibacterial activity study. According to the method steps recommended by the National Committee for Clinical Laboratory Standards (NCCLS) of the United States, the MIC values and MBC values of monomers, pharmaceutical combinations and antibiotic drugs were determined by the microbroth dilution method using a 96-well plate.

[0040] (2) The fractional inhibitory concentration index (FICI) of the combined drugs was determined by the checkerboard dilution method. The fractional inhibitory concentration index (FICI) of each row and column was calculated based on the minimum drug concentration in the wells where no bacterial growth was observed after combination. FICI interpretation criteria: FICI ≤ 0.5, synergistic effect; 0.5 < FICI < 1, partial synergism; FICI = 1, additive effect; 1 < FICI < 4, no relevant effect; FICI ≥ 4, antagonistic effect. The results are shown in Table 1.

[0041] Strains: Escherichia coli ETEC-O78K80 (CICC10421), CICC10302, purchased from the China Center for Industrial Culture Collection of Microorganisms; Salmonella pullorum BNCC124693, purchased from Beijing Beina Chuanglian Biotechnology Research Institute; Salmonella paratyphi B CMCC(B)50094, purchased from the China General Microbiological Culture Collection Center;

[0042] From the fecal samples of diseased chickens in a chicken farm in Ningxia, two strains of Escherichia coli were isolated and identified by enrichment culture in TSB nutrient broth, streak isolation on blood plates, identification using MacConkey plate chromogenic medium, and single colony isolation and identification using a Vitek microbial analyzer, namely clinical isolate 1 and clinical isolate 2.

[0043] Table 1 Results of Drug MIC, MBC and FICI Index

[0044]

[0045]

[0046] Note: Artemisic acid (AA); Imipenem and Cilastatin Sodium (ICS).

[0047] The results in Table 1 show that the active monomer has a significant antibacterial and sensitizing effect. By using the combination of active monomer and imipenem / cilastatin sodium, the dosage of active monomer and imipenem / cilastatin sodium can be reduced, effectively reversing bacterial resistance. The effect is significantly better than using active monomer or antibiotic alone, and it has a synergistic promoting effect.

[0048] Example 8

[0049] Construction of animal models of inflammation and study on the anti-inflammatory activity of drugs

[0050] (1) Animals and drugs: Fifty BALB / c female mice of similar weight (20±2g), SPF grade, 4-6 weeks old (within 3 days after weaning) were selected and randomly divided into 5 groups of 10 mice each. All groups were fed a basal diet. See Table 2 for details.

[0051] The pharmaceutical composition of Example 6 was selected for this experimental study.

[0052] Control group: Ciprofloxacin hydrochloride (0.05%, w / v, CIPH, batch number: 20220509), dose 0.01 mg / g BW (ip), purchased from Jiangsu Zhongmu Beikang Pharmaceutical Co., Ltd.

[0053] Forty minutes after the last administration, mice were intravenously injected (iv) with 0.1 mL of 1% Evans blue solution and intraperitoneally injected (ip) with 0.2 mL of 0.7% glacial acetic acid solution. Twenty minutes later, the mice were euthanized by cervical dislocation, and the peritoneal cavity was flushed with 5 mL of physiological saline. The eluent was collected and centrifuged at 3000 rpm for 5 min. The absorbance (A) of the supernatant was measured at 580 nm using a microplate reader. The results are shown in Table 2.

[0054] Table 2. Effects of the drug composition injection on peritoneal capillary permeability in young mice (mean ± SD, n = 10)

[0055]

[0056]

[0057] Note: The bacterial agent injected into the drug control group, high-dose treatment group, medium-dose treatment group, and low-dose treatment group was Escherichia coli ETEC-O78K80 (CICC10421).

[0058] As shown in Table 2, compared with the control group, the high, medium, and low dose groups of the drug composition significantly reduced the A value of peritoneal lavage fluid (P<0.05, P<0.01), and the high and medium dose groups had effects comparable to ciprofloxacin hydrochloride. The results indicate that the drug composition injection can significantly reduce the increase in capillary permeability in young mice induced by glacial acetic acid solution and has a significant anti-inflammatory effect on acute exudative inflammation.

[0059] Example 9

[0060] Acute toxicity test of the drug composition by intraperitoneal injection in mice

[0061] (1) Experimental methods: The acute toxicity of the drug composition injection to mice was evaluated using the maximum tolerated dose (MTD) method, according to the method in the "Compilation of Technical Guidelines for Veterinary Drug Research" (Veterinary Drug Evaluation Center of the Ministry of Agriculture of the People's Republic of China, 2020 edition). Twenty BALB / c mice (20±2g) of similar weight, SPF grade, half male and half female, were used in this experiment and were isolated and acclimatized for 7 days.

[0062] (2) Administration: After fasting overnight, the mice were administered the drug composition via subcutaneous intraperitoneal injection three times within one day, with each dose 6 hours apart, for a total of 2.0 mL per mouse. General behavior of the mice was recorded 4 hours after administration, and then every 24 hours for 7 days. All animals were sacrificed at the end of the experiment, and gross pathological changes in vital organs and tissues (heart, lungs, liver, kidneys, spleen, thymus, ovaries / fallopian tubes or testes, gastrointestinal tract) were observed. Histopathological examination was performed when significant pathological changes were observed in these organs.

[0063] (3) Acute toxicity results:

[0064] During the 7-day trial, no deaths or abnormal behaviors (drowsiness, sleep, coma, tremors, and diarrhea) were observed in the mice. Furthermore, gross examination of the mice's heart, lungs, liver, kidneys, spleen, thymus, ovaries / fallopian tubes or testes, and gastrointestinal tract revealed no obvious pathological changes in color or texture, and no typical inflammatory lesions. Therefore, it can be inferred that the injectable pharmaceutical composition of this invention (Example 6) has extremely low toxicity when administered via in vitro percutaneous intraperitoneal injection, and a high clinically safe dosage.

[0065] Example 10

[0066] Clinical application of pharmaceutical compositions

[0067] In this embodiment, the experimental group of sick chickens was fed the oral solution and injection of the drug composition provided in Example 6. The control group of sick chickens was fed enrofloxacin hydrochloride (ethylciprofloxacin, EN-H, batch number: 20220325), which was purchased from Shanghai Yiyuan Biopharmaceutical Co., Ltd.

[0068] At a chicken farm in Huazangsi Town, Tianzhu Tibetan Autonomous County, Gansu Province, 600 Hy-Line Brown chickens suffering from salpingitis at 320 days old were selected and raised in cages with 7-10 chickens per cage.

[0069] Inclusion criteria: Before the start of the experiment, sick chickens showed signs of depression, ruffled feathers, loss of appetite, inability to stand, difficulty walking, and yellowish-white, foul-smelling feces sticking to the vent. The cloaca of dead chickens was everted and congested. Sick chickens laid poor-quality eggs, such as blood-spotted eggs, thin-shelled eggs, soft-shelled eggs, sandy-shelled eggs, deformed eggs, and white-shelled eggs, showing characteristics of oviductitis with low egg production rate. The daily rate of substandard eggs was about 15%.

[0070] Laying hens before drug administration served as the blank control group (before drug administration), while those after drug administration served as the experimental control group (drug administration phase and drug withdrawal phase). See Table 3 for details.

[0071] Dosage and method:

[0072] (A) Intraperitoneal injection (ip): Before use, dilute 1 part sterile aliquot (2 mL / part) with 18 mL of sterile saline (1:10 dilution). Dosage: 10 mL / animal, once a day, for 5 days as one course of treatment. Observe continuously for 15 days.

[0073] (B) Oral solution administration via drinking water: The dosage is 1 part sterile dispensing solution / 1L of drinking water (take the medication when thirsty, depending on the amount of water consumed), and one course of treatment is 7 days. Observe continuously for 15 days.

[0074] (C) Control drug administration via drinking water: The dosage is 1g / 20L of drinking water, mixed with drinking water (the medication is administered by thirst method according to the amount of water consumed), 7 days is one course of treatment, and the observation is carried out continuously for 15 days.

[0075] Efficacy evaluation criteria

[0076] (A) Cured: After medication, the symptoms of the sick chickens disappeared, their spirit and appetite returned to normal, eggshell quality was normal, egg production rate increased, and the number of poor-quality eggs decreased. There were no abnormal secretions in the oviducts and no contaminants around the anus. Necropsy revealed no visible lesions in the follicles and oviducts, and there was no recurrence within 7 days of stopping the medication.

[0077] (B) Effective: After medication, the symptoms of the sick chickens improved significantly, their spirit and appetite returned to normal, the egg production rate increased, the number of poor-quality eggs decreased, and there was a relapse during the observation period after medication was stopped.

[0078] (C) Ineffective: After medication, the symptoms of sick chickens are not relieved, or even worsen or cause death; the egg production rate does not change or continues to decline; and the quality of inferior eggs does not change or increases.

[0079] Observation indicators:

[0080] (A) Egg production rate: Eggs are collected and counted at fixed times each day. Egg production rate = number of eggs produced that day divided by the total number of laying hens in the henhouse.

[0081] (B) Defective egg rate: Eggs are collected daily at set times, and the number of defective eggs is counted. Defective egg rate = number of defective eggs divided by the total number of laying hens in the henhouse.

[0082] Table 3. Treatment results of the drug composition on oviductitis and peritonitis in laying hens.

[0083]

[0084] Table 3 shows that no adverse reactions were observed in the affected laying hens during the administration period and for a period after drug withdrawal. After 5-7 days of treatment, the cure rate of the preparation product in Example 6 of this invention reached over 85%, which was similar to the efficacy of the control drug enrofloxacin hydrochloride, with no significant difference. After the treatment period, the symptoms of the cured laying hens in both the treatment group and the control group disappeared, their mental state and appetite returned to normal, there were no abnormal secretions from the oviducts, and no contaminants around the anus. Eggshell quality was normal, egg production rate rebounded, and the number of inferior eggs decreased significantly.

[0085] The results showed that the formulation in Example 6 significantly improved the egg production rate of laying hens, with an increase of 13%–15%; the number of defective eggs and their proportion in the total daily egg production were significantly reduced. In the pre-treatment phase of this experiment, the defective egg rate ranged from 15.08% to 17.29%. With treatment and a one-week withdrawal period, the defective egg rate gradually decreased and stabilized. At the end of the experiment, the defective egg rate remained stable between 3.29% and 4.78%, indicating a relatively ideal treatment effect.

[0086] As demonstrated by the above embodiments, the pharmaceutical composition prepared in this invention can treat oviduct inflammation, peritonitis, and secondary intestinal infections in laying hens through antimicrobial infection and anti-inflammatory pathways, significantly improving the laying performance of hens. After administration, the medication shows rapid efficacy, a significant increase in egg production rate, and a significant decrease in the rate of substandard eggs. It can effectively address common oviduct inflammation and peritonitis in laying hens over 300 days old, is safe and reliable for clinical use, and can improve the quality and safety of poultry and egg products, which is particularly important for large-scale laying hen farms.

[0087] The above description is merely a preferred embodiment of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A pharmaceutical composition for treating oviductitis and peritonitis in laying hens, characterized in that, The pharmaceutical composition comprises the following raw materials in parts by weight: 2-10 parts artemisinic acid, 1-10 parts leonurine hydrochloride, 1-10 parts sodium salicylate, and 0.001-0.005 parts imipenem / cilastatin sodium.

2. The pharmaceutical composition according to claim 1, characterized in that, The pharmaceutical composition also includes the following excipients in parts by weight: 5-10 parts sodium chloride, 10-30 parts sodium bicarbonate, and 1-3 parts sodium bisulfite.

3. The pharmaceutical composition according to claim 1 or 2, characterized in that, The pharmaceutical composition is an oral or injectable formulation.

4. The pharmaceutical composition according to claim 3, characterized in that, Each 100 mL of the oral or injectable preparation comprises the following ingredients by weight: 2-10 g artemisinic acid, 1-10 g leonurine hydrochloride, 1-10 g sodium salicylate, 0.001-0.005 g imipenem / cilastatin sodium, 5-10 g sodium chloride, 10-30 g sodium bicarbonate, and 1-3 g sodium bisulfite.

5. A method for preparing the pharmaceutical composition according to claim 4, characterized in that, Includes the following steps: Artemisinic acid, imipenem / cilastatin sodium, leonurine hydrochloride, sodium salicylate, sodium chloride, sodium bicarbonate, and sodium bisulfite are added to water for injection to adjust the pH to 6.5-7.

0. Then, water for injection is added to bring the volume to a final level, the mixture is filtered for sterilization, and then packaged.

6. The method for preparing the pharmaceutical composition according to claim 5, characterized in that, The filtration and sterilization process involves using a sterile membrane filter with a pore size of 0.2–0.25 μm.

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