CN119792261B - Antibacterial agent for treating urinary infection, and preparation method and application thereof - Google Patents
Antibacterial agent for treating urinary infection, and preparation method and application thereof Download PDFInfo
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Abstract
The invention belongs to the technical field of antibacterial products, and particularly relates to an antibacterial agent for treating urinary infection, and a preparation method and application thereof. The antibacterial agent for treating urinary infection consists of chlorhexidine and calcium liquid, wherein the mass ratio of the chlorhexidine to the calcium liquid is 0.4-0.7:100, and the concentration of the calcium liquid is 0.05g/100 mL-0.5 g/100mL. The antibacterial agent for urinary infection prepared by the invention can treat staphylococcus aureus, escherichia coli, candida albicans, pseudomonas aeruginosa and bacillus subtilis, and especially can treat methicillin-resistant staphylococcus aureus, thereby treating the infection caused by the bacteria.
Description
Technical Field
The invention belongs to the technical field of antibacterial products, and particularly relates to an antibacterial agent for treating urinary infection, and a preparation method and application thereof.
Background
Urinary tract infection refers to an infectious disease caused by abnormal reproduction of pathogens in the urinary tract. The most common pathogens for urinary infections are bacteria, of which escherichia coli is the predominant pathogen, and proteus, klebsiella, staphylococcus and the like are also common bacteria causing urinary infections. In addition to bacteria, fungi, viruses, chlamydia, mycoplasma, etc. may also cause urinary infections. Fungal urinary infections often occur in patients with prolonged antibiotic use, immune dysfunction or indwelling catheters. Urinary infection brings a lot of inconvenience to the daily life of patients and seriously affects the quality of life of patients, so the treatment of urinary infection has important significance.
Currently, therapeutic agents for urinary infections are mainly antibacterial agents. Antibacterial drugs include β -lactams such as penicillins, cephalosporins, etc. which exert antibacterial action by inhibiting bacterial cell wall synthesis, quinolones which inhibit bacterial DNA gyrase and topoisomerase IV, which inhibit DNA replication, which have good antibacterial activity against gram-negative bacteria and part of gram-positive bacteria, and sulfonamides which act by interfering with folic acid metabolism of bacteria to inhibit bacterial growth and reproduction. The above-mentioned antibacterial agent has the advantages of quick effect, broad antibacterial spectrum, etc., but if the antibacterial agent is used too much, some patients develop drug resistance, so it is necessary to continue developing new antibacterial agents.
Disclosure of Invention
In order to solve the technical problems, the invention provides an antibacterial agent for treating urinary infection, and a preparation method and application thereof.
The invention aims to provide an antibacterial agent for treating urinary infection, which consists of chlorhexidine and calcium liquid, wherein the mass ratio of the chlorhexidine to the calcium liquid is 0.4-0.7:100, and the concentration of the calcium liquid is 0.05-0.5 g/100mL.
Calcium in the calcium liquid is used for regulating cellular metabolic activity, enhancing the antibacterial capability of chlorhexidine and reducing the drug resistance of drug-resistant bacteria to chlorhexidine. The antibacterial agent for treating urinary infection of the present invention is suitable for inhibiting at least one of staphylococcus aureus, escherichia coli, candida albicans, pseudomonas aeruginosa and bacillus subtilis. The antibacterial agent of the present invention is also useful for inhibiting methicillin-resistant staphylococcus aureus which is resistant to chlorhexidine, wherein the methicillin-resistant staphylococcus aureus is an MRSA strain.
Preferably, the above antibacterial agent for treating urinary infection is calcium gluconate liquid or calcium citrate liquid, which are organic calcium besides calcium, and have better solubility and absorbability than inorganic calcium such as calcium carbonate.
Preferably, the concentration of the calcium gluconate liquid of the antibacterial agent for treating urinary infection is 0.06g/100 mL-0.5 g/100mL.
Preferably, the concentration of the calcium citrate liquid of the antibacterial agent for treating urinary infection is 0.05g/100 mL-0.06 g/100mL.
Preferably, the above antibacterial agent for treating urinary tract infection, the solvent of the calcium liquid is sterile water.
The invention provides a preparation method of the antibacterial agent for treating urinary infection, which comprises the steps of preparing chlorhexidine and calcium liquid according to the mass ratio, and mixing to obtain the antibacterial agent for treating urinary infection.
The invention provides application of the antibacterial agent for treating urinary infection, which is to mix the antibacterial agent for treating urinary infection with pharmaceutically acceptable auxiliary materials to prepare antibacterial liquid medicine.
Preferably, the antibacterial agent for treating urinary infection is applied by using an antibacterial agent, wherein the antibacterial agent is an external lotion.
Preferably, the auxiliary materials corresponding to the external lotion comprise at least one of (a) - (d):
(a) The buffering agent, such as a citric acid-sodium citrate buffering system, has a pH of 4.5-8.0, and is beneficial to reducing irritation to the urethra and bladder mucosa. The proper pH environment is also beneficial to the activity of chlorhexidine and calcium liquid.
(B) Surfactants such as sodium laureth sulfate have good cleaning and emulsifying action.
(C) Humectants, such as glycerin, can absorb moisture from the surrounding environment and maintain the moist state of the mucosa.
(D) Preservatives, such as potassium sorbate, are used to prevent the topical lotion from being contaminated during storage and use.
Compared with the prior art, the invention has the following beneficial effects:
The antibacterial agent for treating urinary infection provided by the invention consists of chlorhexidine and calcium liquid, wherein the mass ratio of the chlorhexidine to the calcium liquid is 0.4-0.7:100, and the concentration of the calcium liquid is 0.05g/100 mL-0.5 g/100mL. The invention achieves the aim of treating urinary infection by inhibiting at least one of staphylococcus aureus, escherichia coli, candida albicans, pseudomonas aeruginosa and bacillus subtilis, and has good antibacterial effect on methicillin-resistant staphylococcus aureus and wide application prospect. In addition, the antibacterial effect of the antibacterial agent for treating urinary infection can reduce the survival time of pathogenic bacteria in the environment, reduce the spreading risk of pathogenic bacteria and protect susceptible people.
The invention also provides application of the antibacterial agent for urinary infection in preparing external washing liquid, and the external washing liquid has at least the advantages of (1) removing dirt and peculiar smell, keeping clean of cleaning parts, (2) preventing and treating urinary infection, relieving inflammatory reaction, (3) relieving discomfort such as itching, red swelling and the like, and (4) being simple in using method, being used for local application and having small side effect.
Drawings
FIG. 1 is a plate diagram of a control group of methicillin-resistant Staphylococcus aureus in bacteriostasis experiments.
Fig. 2 is a plan view of an antibacterial test of methicillin-resistant staphylococcus aureus of test group 1.
Fig. 3 is a plan view of an antibacterial experiment of methicillin-resistant staphylococcus aureus of experimental group 2.
Fig. 4 is a plan view of an antibacterial experiment of methicillin-resistant staphylococcus aureus of experimental group 3.
Fig. 5 is a plan view of an antibacterial experiment of methicillin-resistant staphylococcus aureus of experimental group 4.
Fig. 6 is a plan view of an antibacterial experiment of methicillin-resistant staphylococcus aureus of experimental group 5.
Fig. 7 is a plan view of an antibacterial experiment of methicillin-resistant staphylococcus aureus of experimental group 6.
Fig. 8 is a plan view of an antibacterial experiment of methicillin-resistant staphylococcus aureus of experimental group 7.
Fig. 9 is a plan view of an antibacterial experiment of methicillin-resistant staphylococcus aureus of experimental group 8.
Fig. 10 is a plan view of an antibacterial test of methicillin-resistant staphylococcus aureus of test group 9.
Fig. 11 is a plan view of an antibacterial test of methicillin-resistant staphylococcus aureus of test group 10.
Fig. 12 is a plan view of an antibacterial test of methicillin-resistant staphylococcus aureus of test group 11.
Fig. 13 is a plan view of an antibacterial test of methicillin-resistant staphylococcus aureus of test group 12.
Fig. 14 is a plan view of an antibacterial test of methicillin-resistant staphylococcus aureus of test group 13.
Fig. 15 is a plan view of an antibacterial test of methicillin-resistant staphylococcus aureus of test group 14.
Detailed Description
In order that those skilled in the art will better understand the technical scheme of the present invention, the present invention will be further described with reference to specific embodiments and drawings.
In the description of the present invention, unless otherwise specified, all reagents are commercially available and methods are conventional in the art.
Example 1
An antibacterial agent for treating urinary infection comprises chlorhexidine 0.4g and calcium liquid 100mL, wherein the calcium liquid is calcium citrate liquid with concentration of 0.05g/100mL, and the solvent of the calcium citrate liquid is sterile water.
The preparation method of the antibacterial agent for treating the urinary infection comprises the steps of preparing 0.4g of chlorhexidine and 100mL of calcium liquid, and mixing to obtain the antibacterial agent for treating the urinary infection.
Example 2
An antibacterial agent for treating urinary infection comprises chlorhexidine 0.5g and calcium liquid 100mL, wherein the calcium liquid is calcium citrate liquid with concentration of 0.05g/100mL, and the solvent of the calcium citrate liquid is sterile water.
The preparation method of the antibacterial agent for treating the urinary infection comprises the steps of preparing 0.5g of chlorhexidine and 100mL of calcium liquid, and mixing to obtain the antibacterial agent for treating the urinary infection.
Example 3
An antibacterial agent for treating urinary infection comprises chlorhexidine 0.6g and calcium liquid 100mL, wherein the calcium liquid is calcium citrate liquid with concentration of 0.05g/100mL, and the solvent of the calcium citrate liquid is sterile water.
The preparation method of the antibacterial agent for treating the urinary infection comprises the steps of preparing 0.6g of chlorhexidine and 100mL of calcium liquid, and mixing to obtain the antibacterial agent for treating the urinary infection.
Example 4
An antibacterial agent for treating urinary infection comprises chlorhexidine 0.7g and calcium liquid 100mL, wherein the calcium liquid is calcium citrate liquid with concentration of 0.05g/100mL, and the solvent of the calcium citrate liquid is sterile water.
The preparation method of the antibacterial agent for treating the urinary infection comprises the steps of preparing 0.7g of chlorhexidine and 100mL of calcium liquid, and mixing to obtain the antibacterial agent for treating the urinary infection.
Example 5
An antibacterial agent for treating urinary infection comprises chlorhexidine 0.4g and calcium liquid 100mL, wherein the calcium liquid is calcium citrate liquid with concentration of 0.06g/100mL, and the solvent of the calcium citrate liquid is sterile water.
The preparation method of the antibacterial agent for treating the urinary infection comprises the steps of preparing 0.4g of chlorhexidine and 100mL of calcium liquid, and mixing to obtain the antibacterial agent for treating the urinary infection.
Example 6
An antibacterial agent for treating urinary infection comprises chlorhexidine 0.4g and calcium liquid 100mL, wherein the calcium liquid is calcium gluconate liquid with concentration of 0.05g/100mL, and the solvent of the calcium gluconate liquid is sterile water.
The preparation method of the antibacterial agent for treating the urinary infection comprises the steps of preparing 0.4g of chlorhexidine and 100mL of calcium liquid, and mixing to obtain the antibacterial agent for treating the urinary infection.
Example 7
An antibacterial agent for treating urinary infection comprises chlorhexidine 0.5g and calcium liquid 100mL, wherein the calcium liquid is calcium gluconate liquid with concentration of 0.05g/100mL, and the solvent of the calcium gluconate liquid is sterile water.
The preparation method of the antibacterial agent for treating the urinary infection comprises the steps of preparing 0.5g of chlorhexidine and 100mL of calcium liquid, and mixing to obtain the antibacterial agent for treating the urinary infection.
Example 8
An antibacterial agent for treating urinary infection comprises chlorhexidine 0.6g and calcium liquid 100mL, wherein the calcium liquid is calcium gluconate liquid with concentration of 0.05g/100mL, and the solvent of the calcium gluconate liquid is sterile water.
The preparation method of the antibacterial agent for treating the urinary infection comprises the steps of preparing 0.6g of chlorhexidine and 100mL of calcium liquid, and mixing to obtain the antibacterial agent for treating the urinary infection.
Example 9
An antibacterial agent for treating urinary infection comprises chlorhexidine 0.7g and calcium liquid 100mL, wherein the calcium liquid is calcium gluconate liquid with concentration of 0.05g/100mL, and the solvent of the calcium gluconate liquid is sterile water.
The preparation method of the antibacterial agent for treating the urinary infection comprises the steps of preparing 0.7g of chlorhexidine and 100mL of calcium liquid, and mixing to obtain the antibacterial agent for treating the urinary infection.
Example 10
An antibacterial agent for treating urinary infection comprises chlorhexidine 0.4g and calcium liquid 100mL, wherein the calcium liquid is calcium gluconate liquid with concentration of 0.1g/100mL, and the solvent of the calcium gluconate liquid is sterile water.
The preparation method of the antibacterial agent for treating the urinary infection comprises the steps of preparing 0.4g of chlorhexidine and 100mL of calcium liquid, and mixing to obtain the antibacterial agent for treating the urinary infection.
Example 11
An antibacterial agent for treating urinary infection comprises chlorhexidine 0.4g and calcium liquid 100mL, wherein the calcium liquid is calcium gluconate liquid with concentration of 0.5g/100mL, and the solvent of the calcium gluconate liquid is sterile water.
The preparation method of the antibacterial agent for treating the urinary infection comprises the steps of preparing 0.4g of chlorhexidine and 100mL of calcium liquid, and mixing to obtain the antibacterial agent for treating the urinary infection.
The main differences between the above examples are shown in table 1. In table 1, the conditions of other experimental groups were also set, wherein the control group was sterile water, the chlorhexidine group was a liquid after chlorhexidine was dispersed in sterile water, the calcium gluconate liquid group was a liquid after calcium gluconate was dispersed in sterile water, and the calcium citrate liquid group was a liquid after calcium citrate was dispersed in sterile water. Examples 1-4 differ in the mass ratio of chlorhexidine to calcium citrate liquid in order to investigate the effect of the mass ratio of different chlorhexidine and calcium citrate liquids on the bacteriostatic effect. Examples 1 and 5 used different calcium citrate liquid concentrations to investigate the effect of different calcium citrate liquid concentrations on bacteriostatic effects. Examples 6-9 differ in the mass ratio of chlorhexidine to calcium gluconate liquid in order to investigate the effect of different mass ratios of chlorhexidine to calcium gluconate liquid on the bacteriostatic effect. Examples 5, 10 and 11 use different calcium gluconate liquid concentrations to investigate the effect of different calcium gluconate liquid concentrations on the bacteriostatic effect.
Table 1 formulations of different experimental groups
1. Antibacterial experiments of methicillin-resistant staphylococcus aureus.
(1) The name of the strain is methicillin-resistant staphylococcus aureus.
(2) Preparation of bacterial suspension
The preparation of the material comprises the step of activating methicillin-resistant staphylococcus aureus. Meanwhile, preparing a sodium chloride solution with the mass fraction of 0.9%, and sterilizing the sodium chloride solution to obtain the sterile normal saline.
The operation steps are that the activated strain is picked up and placed in a sterile test tube filled with sterile physiological saline. The bacterial suspension is formed by uniformly dispersing bacterial cells by using a vortex oscillator for oscillation. The concentration of the bacterial suspension is adjusted by using sterile physiological saline until the concentration of the bacterial suspension is adjusted to be 2.0X10 4 cfu/mL.
(3) Antibacterial rate detection
In the detection process, 100 mu L of prepared bacterial suspension with the concentration of 2.0X10 4 cfu/mL is taken in an ultra-clean workbench, added into 5mL of liquid to be detected, uniformly mixed to obtain a mixed sample, after 20min, 0.5mL of the mixed sample is absorbed and added into a nutrient agar culture medium with the temperature of 42 ℃, after uniform mixing, the mixed sample is poured into a culture dish, and after the nutrient agar culture medium is solidified, the culture is carried out for 48h at the temperature of 37 ℃. After the cultivation is finished, counting the colony number of the living bacteria. The test was repeated three times, and the average value of the number of colonies of viable bacteria was taken.
The bacteriostasis rate was calculated according to the following formula:
。
The results of the measurements are shown in Table 2. The bacteriostasis experiment flat plate diagram of methicillin-resistant staphylococcus aureus is shown in figures 1-15.
TABLE 2 antibacterial Rate of methicillin-resistant Staphylococcus aureus
Methicillin-resistant staphylococcus aureus is a multi-drug resistant bacterium, and the hazards presented by the bacterium are mainly manifested in the following aspects.
(1) Clinical treatment is difficult because methicillin-resistant staphylococcus aureus is resistant to a variety of common antibiotics, including methicillin, for which common penicillin and cephalosporin antibiotics are generally ineffective. Treatment with expensive and more toxic side effects antibiotics such as vancomycin, linezolid, etc. is required. It is therefore necessary to develop new methicillin-resistant staphylococcus aureus antibacterial agents.
(2) High morbidity and mortality, and methicillin-resistant staphylococcus aureus can infect people of various ages and health conditions. The resistance of special people such as hospitalized patients, old people, children and the like is poor, and once the special people are infected with methicillin-resistant staphylococcus aureus, the disease condition tends to develop rapidly, so that higher morbidity and mortality are caused. In addition, methicillin-resistant staphylococcus aureus can cause serious infections such as skin and soft tissue infections, blood flow infections, pneumonia, osteomyelitis, endocarditis, and the like. In the case of blood flow infection, bacteria can spread to various organs of the whole body along with blood circulation after entering blood, and systemic inflammatory response syndrome is caused, and when severe, infectious shock and multiple organ failure can be caused.
Given that methicillin-resistant staphylococcus aureus now exhibits a drug resistance to chlorhexidine, there is a need to develop products that can improve chlorhexidine resistance. The antibacterial agent for treating urinary infection provided by the invention has an inhibition effect on methicillin-resistant staphylococcus aureus, reduces the infection symptoms of the methicillin-resistant staphylococcus aureus, can improve the respiratory function and improve the life quality of patients.
2. Bacteriostasis experiments of other strains.
(1) Name of the strain
Staphylococcus aureus ATCC6538, escherichia coli ATCC25922, candida albicans ATCC10231, pseudomonas aeruginosa ATCC9027 and bacillus subtilis ATCC21394.
(2) Preparation of bacterial suspension
Material preparation Staphylococcus aureus ATCC6538, escherichia coli ATCC25922, candida albicans ATCC1023, pseudomonas aeruginosa ATCC9027 and Bacillus subtilis ATCC21394 were activated respectively. Meanwhile, preparing a sodium chloride solution with the mass fraction of 0.9%, and sterilizing the sodium chloride solution to obtain the sterile normal saline.
The operation steps are that the activated strains are picked and respectively put into a sterile test tube filled with sterile physiological saline. The bacterial suspension is formed by uniformly dispersing bacterial cells by using a vortex oscillator for oscillation. The concentration of the bacterial suspension was adjusted with sterile physiological saline until the bacterial suspension concentration of each strain was adjusted to 2.0X10 4 cfu/mL.
(3) Antibacterial rate detection
In the detection process, 100 mu L of prepared bacterial suspension with the concentration of 2.0X10 4 cfu/mL is taken in an ultra-clean workbench, added into 5mL of liquid to be detected, uniformly mixed to obtain a mixed sample, after 20min, 0.5mL of the mixed sample is absorbed for gradient dilution, the liquid before and after dilution is respectively added into a culture medium with the temperature of 42 ℃, after uniform mixing, the mixture is poured into a culture dish, and after the culture medium is solidified, the culture is carried out at the temperature of 35 ℃. Wherein, the culture mediums adopted by staphylococcus aureus ATCC6538, escherichia coli ATCC25922, pseudomonas aeruginosa ATCC9027 and bacillus subtilis ATCC21394 are nutrient agar culture mediums, the culture time of 35 ℃ is 48 hours, the culture medium adopted by candida albicans ATCC10231 is a sand agar culture medium, and the culture time of 35 ℃ is 72 hours. After the cultivation is finished, counting the colony number of the living bacteria. The test was repeated three times, and the average value of the number of colonies of viable bacteria was taken.
The test results are shown in Table 3. The liquids to be tested for each experimental group in table 3 are referred to in table 1.
TABLE 3 antibacterial Rate of other strains
The results in Table 3 show that the antibacterial agents for treating urinary infections of example 1 to example 11 have excellent inhibitory effects on Staphylococcus aureus, escherichia coli, candida albicans, pseudomonas aeruginosa, and Bacillus subtilis.
Among urinary infections, staphylococcus aureus, escherichia coli, candida albicans, pseudomonas aeruginosa and bacillus subtilis are common pathogenic bacteria. Effective against these pathogens, has at least the following benefits for urinary tract infections.
(1) Eliminating infection source
The mass propagation of bacteria such as staphylococcus aureus, escherichia coli, pseudomonas aeruginosa and bacillus subtilis can destroy tissues such as urinary tract mucous membrane and the like, and cause inflammation. When these bacteria are effectively inhibited, the number of bacteria is greatly reduced and mass reproduction cannot be continued, thereby reducing direct damage to the tissue.
(2) Relieving symptoms
When the urinary system is infected, the patients often have symptoms such as frequent urination, urgent urination, painful urination and the like due to the stimulation of bacteria. When the pathogenic bacteria are eliminated, the inflammation of the urinary tract mucosa gradually subsides, the irritation to the bladder and the urethra is lightened, and the urination abnormality is lightened. For example, cystitis caused by infection with pseudomonas aeruginosa is frequently and intentionally caused by urination and is painful in urination, and after the bacteria are inhibited, the inflammation of the bladder mucosa is improved, and the symptoms of frequent urination and painful urination are relieved. Some patients have urinary infection, and can also cause general symptoms such as lower abdominal pain, sense of distention, fever, chills and the like. Toxins produced by pathogens such as staphylococcus aureus can enter the blood and affect the whole body. After the bacteria are inhibited, the toxin production is reduced, and the immune response of the body is gradually recovered to be normal, thereby being beneficial to relieving the discomfort of the lower abdomen, reducing the body temperature, relieving the systemic symptoms and recovering the body of the patient to be in a comfortable state.
(3) Preventing complications
If the infection caused by staphylococcus aureus, escherichia coli, pseudomonas aeruginosa and bacillus subtilis is not effectively controlled, bacteria can up-infect the kidneys to cause serious diseases such as pyelonephritis. For example, bacteria such as Escherichia coli destroy kidney tissues and affect kidney functions after infecting the kidney. The bacteria can be inhibited in time, the spread of infection to the kidney can be effectively prevented, the normal structure and function of the kidney can be protected, and serious complications such as renal hypofunction, renal abscess and the like can be prevented. When bacteria in the blood multiply, sepsis may be initiated, a serious and potentially life threatening disease. Staphylococcus aureus, pseudomonas aeruginosa and the like have strong pathogenicity, and if not inhibited in time during urinary infection, the staphylococcus aureus, pseudomonas aeruginosa and the like can enter blood, and severe patients can induce septicemia. Therefore, the occurrence risk of septicemia can be obviously reduced by inhibiting the germs, and the life safety of patients is ensured.
In conclusion, the antibacterial agent for treating urinary infection provided by the invention can effectively inhibit staphylococcus aureus, escherichia coli, pseudomonas aeruginosa and bacillus subtilis, especially methicillin-resistant staphylococcus aureus, so that urinary infection can be effectively prevented and treated.
It should be noted that, when numerical ranges are referred to in the present invention, it should be understood that two endpoints of each numerical range and any numerical value between the two endpoints are optional, and because the adopted step method is the same as the embodiment, in order to prevent redundancy, the present invention describes a preferred embodiment. While the preferred embodiments of the present invention have been described, additional variations and modifications in those embodiments may occur to those skilled in the art once they learn of the basic inventive concepts, which fall within the scope of the invention.
It will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit or scope of the invention. The present invention is intended to include such modifications and alterations insofar as they come within the scope of the equivalent technology thereof.
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