Use of eravacycline in the treatment of streptococcal infections

Abstract

This invention belongs to the field of biomedical technology, specifically disclosing the application of Erastin in the treatment of pyogenic coccal infections. This invention discovers that Erastin, as a host-targeted therapeutic molecule, can enhance the host's immune killing effect, inhibit the proliferation of pyogenic cocci in the host, and inhibit the survival of pyogenic cocci. Therefore, it proposes using the compound Erastin to prepare drugs for the treatment of pyogenic coccal infections, which can not only solve the problem of resistance of most pyogenic cocci to existing antibiotics, but also provide a new technical means for the treatment of purulent infections.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to the application of alastin in the treatment of pyogenic coccal infections. Background Technology

[0002] Pyogenic cocci are a group of bacteria that can cause purulent infections, with Staphylococcus aureus being the main pathogen of pyogenic coccal infections. Pyogenic cocci are commonly found on the human body surface and in the environment, such as on the skin, in the respiratory tract, and in the digestive tract. When the body's immunity is weakened or damaged, pyogenic cocci may invade the body and cause infection.

[0003] Antibiotics are commonly used to treat pyogenic coccal infections. Because different types of pyogenic cocci exhibit varying susceptibility to different antibiotics, drug sensitivity testing is necessary to determine the most effective antibiotic. Furthermore, severe pyogenic coccal infections, such as sepsis and septicemia, require systemic treatment, including the use of immunostimulants and supportive care. However, over time, most pyogenic cocci have developed resistance to existing antibiotics, posing a significant challenge to the treatment of these infections. To address the challenge of antibiotic resistance, in addition to focusing on the rational use of antibiotics and strengthening antibiotic research and development—such as continuously investing in research to address existing antibiotic resistance by finding new antibiotics or modifying existing ones to improve their efficacy—developing novel antibacterial agents that can replace antibiotics can also provide new technological means for the treatment of pyogenic coccal infections. Summary of the Invention

[0004] In view of the shortcomings of the prior art described above, the purpose of this invention is to provide the application of alastin in the treatment of pyogenic coccal infections, to solve the problem of resistance of most pyogenic cocci to existing antibiotics, and to provide a new technical means for the treatment of pyogenic coccal infections.

[0005] To achieve the above and other related objectives, the present invention provides the use of epilastin in the preparation of a medicament for treating pyogenic coccal infections, said medicament containing a safe and effective dose of epilastin and its analogues.

[0006] Furthermore, the safe therapeutic concentration of ellastatin in the drug is less than 20 μM, preferably 0.1 to 20 μM, such as 0.1 μM, 1 μM, 5 μM, 10 μM, or 20 μM.

[0007] Furthermore, the lindane in the drug treats pyogenic coccal infections by enhancing the host's immune killing effect and / or inhibiting the proliferation of pyogenic cocci in the host, and / or by inhibiting the activity and / or survival of pyogenic cocci within host cells.

[0008] Furthermore, the drug, ellastine, treats pyogenic coccal infections by inhibiting the activity and / or survival of pyogenic cocci within macrophages, wherein the macrophages can be isolated macrophages or macrophages in a living animal.

[0009] Furthermore, the pyogenic cocci include Gram-positive bacteria and Gram-negative bacteria. The Gram-positive bacteria include, but are not limited to, Staphylococcus, Streptococcus, and Pneumococcus, while the Gram-negative bacteria include, but are not limited to, Meningococcus and Neisseria gonorrhoeae.

[0010] Furthermore, the pyogenic cocci are Staphylococcus aureus.

[0011] Furthermore, the drug can be a single-component substance or a multi-component substance.

[0012] Furthermore, the drug also includes pharmaceutically acceptable carriers and / or excipients.

[0013] Furthermore, the form of the drug is not particularly limited and can be in various forms such as solid, liquid, gel, semi-liquid, or aerosol.

[0014] Furthermore, the drug is primarily targeted at mammals, preferably rodents, even-toed ungulates, perissodactyls, lagomorphs, primates, etc., with monkeys, apes, or humans being the preferred primates.

[0015] Furthermore, the drug can be administered in various ways, including via the gastrointestinal tract or non-gastrointestinal route. Generally, known routes of administration for each chemical drug are recommended, such as intravenous injection or intraperitoneal injection.

[0016] As described above, the application of the present invention's alastin in the treatment of pyogenic coccal infections has the following beneficial effects:

[0017] This invention provides a novel use for the compound alastine. Further research and experiments on alastine's treatment of pyogenic cocci within macrophages revealed that alastine can effectively inhibit the survival of pyogenic cocci. Therefore, this invention proposes the use of alastine in the preparation of drugs to treat pyogenic coccal infections. As a host-targeted therapeutic molecule, alastine can enhance the host's immune killing effect, inhibit the proliferation of pyogenic cocci in the host, inhibit the survival of pyogenic cocci, and treat purulent infections, thereby solving the problem of resistance to existing antibiotics in most pyogenic cocci and providing a new technical means for the treatment of purulent infections. Attached Figure Description

[0018] Figure 1 The image shown is a graph illustrating the cell viability assay results after 24 hours of treatment with different concentrations of ellastatin in Example 1 of this invention.

[0019] Figure 2 The image shown is a graph illustrating the colony count results of infected cells treated with different concentrations of ellastatin for 24 hours after plating. This is from Example 2 of the present invention. Detailed Implementation

[0020] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0021] Erastin, with the molecular formula C 30 H 31 ClN4O4, with a molecular weight of 547.04, has the following molecular structure:

[0022]

[0023] Currently, ellastatin is widely regarded as a drug with anti-tumor activity, which can exert important biological functions by participating in the generation of reactive oxygen species and autophagy.

[0024] Further research and experiments on the treatment of macrophages infected with pyogenic cocci with alastin revealed a new use for the compound alastin: alastin, as a host-targeted therapy molecule, can enhance the host's immune killing effect, inhibit the proliferation of pyogenic cocci in the host, and inhibit the survival of pyogenic cocci.

[0025] Based on this, the present invention proposes the application of epilastin in the treatment of pyogenic coccal infections. Specifically, one embodiment of the present invention provides the application of epilastin in the preparation of a medicament for treating pyogenic coccal infections, wherein the medicament contains a safe and effective dose of epilastin and its analogues.

[0026] In vitro cell experiments conducted in this invention have shown that ellastatin at concentrations below 20 μM causes minimal cell damage. Therefore, in some embodiments, the safe therapeutic concentration of ellastatin in the drug is less than 20 μM, preferably 0.1–20 μM, such as 0.1 μM, 1 μM, 5 μM, 10 μM, or 20 μM.

[0027] In some embodiments, the medicament in which ellastin is used treats pyogenic coccal infection by enhancing the host’s immune killing effect and / or inhibiting the proliferation of pyogenic cocci in the host, and / or by inhibiting the activity and / or survival of pyogenic cocci in host cells.

[0028] In one specific embodiment, the medicament ellastatin treats pyogenic coccal infection by inhibiting the activity and / or survival of pyogenic cocci within macrophages, wherein the macrophages can be isolated macrophages or macrophages in a living animal.

[0029] In some embodiments, the pyogenic cocci include Gram-positive and Gram-negative bacteria, wherein the Gram-positive bacteria include, but are not limited to, Staphylococcus, Streptococcus, and Pneumococcus, and the Gram-negative bacteria include, but are not limited to, Meningococcus and Neisseria gonorrhoeae.

[0030] In one specific embodiment, the pyogenic coccus is Staphylococcus aureus.

[0031] In some embodiments, the drug may be a single-component substance or a multi-component substance.

[0032] In some embodiments, the medicament further includes a pharmaceutically acceptable carrier and / or excipients.

[0033] In some embodiments, the form of the drug is not particularly limited and can be in various forms such as solid, liquid, gel, semi-liquid, or aerosol.

[0034] In some embodiments, the drug is primarily targeted at mammals, preferably rodents, even-toed ungulates, perissodactyls, lagomorphs, primates, etc., and preferably monkeys, apes, or humans.

[0035] In some embodiments, the drug can be administered in various ways, including via the gastrointestinal tract or non-gastrointestinal route. Generally, known routes of administration for each chemical drug are recommended, such as intravenous injection or intraperitoneal injection.

[0036] The following specific examples illustrate the present invention in detail. It should also be understood that the following examples are only for specific illustrative purposes and should not be construed as limiting the scope of protection of the present invention. Any non-essential improvements and adjustments made by those skilled in the art based on the above description of the present invention are within the scope of protection of the present invention. The specific process parameters, etc., in the following examples are merely examples within a suitable range; that is, those skilled in the art can make appropriate selections within the appropriate range based on the description herein, and are not intended to be limited to the specific values ​​in the examples below.

[0037] It should be noted that the pyogenic cocci used in the following embodiments of the present invention are Staphylococcus aureus, which is an ideal model bacterium for studying purulent infections.

[0038] Example 1

[0039] This embodiment demonstrates the safe therapeutic concentration of epirastine through in vitro experiments, and the specific procedures are as follows:

[0040] I. Experimental Materials

[0041] Cells: RAW264.7 mouse mononuclear macrophages;

[0042] Reagents: Dimethyl sulfoxide (DMSO), DMEM high-glucose cell culture medium, fetal bovine serum, phosphate buffer, and ellastatin powder.

[0043] II. Experimental Procedure

[0044] RAW264.7 cells were seeded into 96-well cell culture plates, 1 x 10⁶ cells per well. 4 Cells were collected; after the cells adhered to the wall, a solution of epirastine (prepared from epirastine powder and DMSO) was added. This experiment set up six experimental groups with epirastine concentrations of 0, 0.1, 1, 5, 10, 20, 40, 60, and 100 μM.

[0045] After adding the drug, the sample was placed in a 37°C constant temperature cell culture incubator and cultured for 24 hours.

[0046] After 24 hours of treatment, CCK-8 reagent was added and incubated for another 30 minutes before cell viability was measured.

[0047] III. Experimental Results

[0048] The cell viability of macrophages treated with ellastatin for 24 hours was measured, and the results are as follows: Figure 1 As shown. From Figure 1 It can be concluded that ellastatin at concentrations below 20 μM causes less cell damage.

[0049] Table 1.

[0050]

[0051] Example 2

[0052] This embodiment demonstrates the effective concentration of alastin for treating pyogenic coccal infections through in vitro experiments. The specific procedures are as follows:

[0053] I. Experimental Materials

[0054] Cells: RAW264.7 mouse mononuclear macrophages;

[0055] Bacteria: Staphylococcus aureus;

[0056] Reagents: Dimethyl sulfoxide (DMSO), DMEM high glucose cell culture medium, fetal bovine serum, phosphate buffer, Elasene powder, Triton X100, TSA medium.

[0057] II. Experimental Procedure

[0058] RAW264.7 cells were seeded into 6-well cell culture plates, 1 x 10⁶ cells per well. 6 One cell; after the cells adhered, Staphylococcus aureus was added at an MOI (multiple of infection) of 0.1 to infect the cells.

[0059] One hour after adding bacteria, alastatin solution (prepared from alastatin powder and DMSO) was added. This experiment set up six experimental groups: alastatin concentration of 1, 5, 10, 20, 40, and 50 μmol / L, and a control group without alastatin.

[0060] After adding the drug, the sample was placed in a 37°C constant temperature cell culture incubator and cultured for 24 hours.

[0061] After 24 hours of treatment, cell lysis buffer (1% Triton PBS solution) was added to release the bacteria. The cell debris and bacterial mixture were resuspended by centrifugation. The cell debris and bacterial pellet were then resuspended in phosphate buffer and serially diluted (10⁻⁶ dilutions). 2 10 3 10 4 After suspension, spread the suspension onto TSA medium.

[0062] III. Experimental Results

[0063] The colony count of infected cells treated with ellastatin was determined 24 hours later, and the results are as follows: Figure 2 As shown in Table 2. From Figure 2 As shown in Table 2, alastin can effectively inhibit the survival of Staphylococcus aureus in macrophages.

[0064] Table 2. Colony counts of infected cells after 24 hours of treatment with different concentrations of ellastatin

[0065]

[0066]

[0067] The experimental results above show that alastin can effectively inhibit the survival of Staphylococcus aureus in macrophages.

[0068] In summary, in vitro experiments have confirmed that the embodiments of the present invention have shown that alastin can effectively inhibit the survival of Staphylococcus aureus in macrophages.

[0069] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.

Claims

1. The use of alastin in the preparation of a medicament for treating pyogenic coccal infections, characterized in that, The active ingredient of the drug is ellastatin, the drug contains a safe and effective dose of ellastatin, the safe therapeutic concentration of ellastatin in the drug is 0.1~20μM, and the pyogenic cocci are Staphylococcus aureus.

2. The application according to claim 1, characterized in that: The drug also includes pharmaceutically acceptable carriers and / or excipients.

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