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CN-121987641-A - Application of combined composition in preparation of medicines for resisting fungal and bacterial infection

CN121987641ACN 121987641 ACN121987641 ACN 121987641ACN-121987641-A

Abstract

The invention relates to application of a combination composition in preparing medicines for resisting fungal and bacterial infection, wherein the active components of the combination composition are antibiotics and antibiotic adjuvants, and the antibiotic adjuvants are tripterine or pharmaceutically acceptable salts thereof. The invention creatively discovers that the tripterine or the medicinal salt thereof can be combined with antibiotics to have excellent effects in antifungal and bacterial infection, especially in antifungal infection, wherein the tripterine or the medicinal salt thereof can enhance the antibacterial effect, especially antifungal effect, of the antibiotics, remarkably increase the antibacterial sensitivity of the antibiotics, inhibit the occurrence of fungus or bacterial drug resistance, and the combination composition is used as an antibiotic adjuvant-antibiotic drug platform, provides a new strategy for realizing efficient antibacterial effect, and has a plurality of application dosage forms and application scenes.

Inventors

  • LIU JING
  • WANG MINGGE

Assignees

  • 国家纳米科学中心

Dates

Publication Date
20260508
Application Date
20241107

Claims (10)

  1. 1. The application of the combination composition in preparing medicines for resisting fungal and bacterial infection is characterized in that the active components of the combination composition are antibiotics and antibiotic adjuvants, and the antibiotic adjuvants are tripterine or pharmaceutically acceptable salts thereof.
  2. 2. The use according to claim 1, wherein the antibiotic comprises any one or a combination of at least two of amphotericin B, nystatin, miconazole, ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, flucytosine, terbinafine, caspofungin, micafungin, anidulafungin, griseofulvin, penicillin, amoxicillin, ampicillin, cefradine, ceftazidime, imipenem, amikacin, gentamicin, doxycycline, tetracycline, minocycline, erythromycin, clarithromycin, azithromycin, sulfadiazine, ciprofloxacin, levofloxacin, metronidazole, clindamycin or fosfomycin.
  3. 3. The use according to claim 1, wherein the fungus comprises any one or a combination of at least two of candida albicans, candida glabrata, candida tropicalis, candida krusei, aspergillus fumigatus, aspergillus niger, aspergillus flavus, aspergillus oryzae, fusarium, cryptococcus neoformans, candida, mucor, histoplasma capsulatum, cercospora, coccidioides, cryptococcus gatus, or paracoccidioidosporic.
  4. 4. The use according to claim 1, wherein the bacteria comprise any one or a combination of at least two of klebsiella pneumoniae, acinetobacter baumannii, pseudomonas aeruginosa, escherichia coli, salmonella, shigella, streptococcus pneumoniae, staphylococcus aureus, mycobacterium tuberculosis, or clostridium difficile.
  5. 5. The use according to claim 1, wherein the molar ratio of antibiotic to antibiotic adjuvant is 1 (0.001-500).
  6. 6. The use according to claim 1, wherein the combination composition is a single compound preparation or a combination of an antibiotic adjuvant and an individual preparation of an antibiotic, and when the combination is a combination of an antibiotic adjuvant and an individual preparation of an antibiotic, the administration mode of the combination can be simultaneous administration, cross administration or sequential administration; Preferably, the dosage form of the formulation comprises an oral dosage form, an injection dosage form or an external dosage form; Preferably, the mode of administration of the drug includes gastrointestinal administration, injection administration, transdermal administration, mucosal administration, inhalation administration or topical administration; preferably, the combination composition further comprises pharmaceutically acceptable excipients; preferably, the auxiliary materials comprise any one or a combination of at least two of carriers, diluents, binders, wetting agents, disintegrants, emulsifiers, cosolvents, solubilizers, osmotic pressure regulators, surfactants, coating materials, colorants, pH regulators, antioxidants, bacteriostats or buffers.
  7. 7. A combination pharmaceutical composition for combating fungal and bacterial infections, characterized in that the active components of said combination pharmaceutical composition are an antibiotic and an antibiotic adjuvant; The antibiotic adjuvant is tripterine or pharmaceutically acceptable salt thereof; The antibiotic is selected from any one or a combination of at least two of amphotericin B, nystatin, miconazole, ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, flucytosine, terbinafine, caspofungin, micafungin, anidulafungin, griseofulvin, penicillin, amoxicillin, ampicillin, cefradine, ceftazidime, imipenem, amikacin, gentamicin, doxycycline, tetracycline, minocycline, erythromycin, clarithromycin, azithromycin, sulfadiazine, ciprofloxacin, levofloxacin, metronidazole, clindamycin or fosfomycin.
  8. 8. The combination pharmaceutical composition according to claim 7, wherein the molar ratio of antibiotic to antibiotic adjuvant is 1 (0.001-500).
  9. 9. The combination pharmaceutical composition of claim 7, wherein the fungus comprises any one or a combination of at least two of candida albicans, candida glabrata, candida tropicalis, candida krusei, aspergillus fumigatus, aspergillus niger, aspergillus flavus, aspergillus oryzae, fusarium, cryptococcus neoformans, candida, mucor, histoplasma capsulatum, cercospora, coccidioides, cryptococcus gatus, or paracoccidioidosporium.
  10. 10. The combination pharmaceutical composition of claim 7, wherein the bacteria comprise any one or a combination of at least two of klebsiella pneumoniae, acinetobacter baumannii, pseudomonas aeruginosa, escherichia coli, salmonella, shigella, streptococcus pneumoniae, staphylococcus aureus, mycobacterium tuberculosis, or clostridium difficile.

Description

Application of combined composition in preparation of medicines for resisting fungal and bacterial infection Technical Field The invention belongs to the field of biological medicine, and relates to application of a combination composition in preparation of a medicine for resisting fungal and bacterial infection. Background Bacterial and fungal infections are important causes of human death, and the discovery of antibiotics greatly reduces the death of patients with bacterial and fungal infections. However, the abuse of antibiotics has led to the rapid development of multi-drug resistant bacteria, which constitutes a long-term threat to human health, sustainable production and development of food. The development difficulty of the novel antibiotics is high, the development period is long, and the clinical treatment of drug-resistant bacteria infection is severely limited. The advent of the latter antibiotic era has prompted us to develop new therapeutic regimens to address the state of optimistically ill-antibiotic resistance. The discovery of antibiotic adjuvants brings hopes for coping with the current situation that the development of novel antibiotics is hindered and the existing medicines are difficult to cope with drug-resistant bacteria infection. The antibiotic adjuvant plays a role in enhancing the curative effect of antibiotics by being combined with the antibiotics, provides new hope for restoring the pharmaceutical activity of the existing antibiotics and inhibiting the generation of drug resistance, and provides an orthogonal strategy for the discovery of novel antibiotics. The tripterygium wilfordii also called Huang Lateng and shikimia aquatica have various effects of dispelling wind and removing dampness, activating blood and removing obstruction in collaterals, relieving swelling and pain, diminishing inflammation and detoxifying and the like. Tripterine (Celastrol, CST), also known as celastrol, is a triterpene active ingredient in Tripterygium wilfordii extract, and has various biological activities. The research shows that the tripterine has the functions of resisting tumor, rheumatoid disease, parkinsonism and the like. With the progressive penetration of research, various medicinal effects of tripterine are continuously developed and applied. Disclosure of Invention In view of the shortcomings of the prior art, the invention aims to provide an application of a combination composition in preparing medicines for resisting fungal and bacterial infection. In order to achieve the aim of the invention, the invention adopts the following technical scheme: In a first aspect, the invention provides application of a combination composition in preparing medicines for resisting fungal and bacterial infection, wherein the active components of the combination composition are antibiotics and antibiotic adjuvants, and the antibiotic adjuvants are tripterine or pharmaceutically acceptable salts thereof. The invention creatively discovers that the tripterine or the medicinal salt thereof can be combined with antibiotics to have excellent effects in antifungal and bacterial infection, especially in antifungal infection, wherein the tripterine or the medicinal salt thereof can enhance the antibacterial effect of the antibiotics, especially antifungal effect, increase the antibacterial sensitivity of the antibiotics, inhibit the occurrence of fungal or bacterial drug resistance, and the combination composition is used as an antibiotic adjuvant-antibiotic drug platform, provides a new strategy for realizing efficient antibacterial effect, and has a plurality of application dosage forms and application scenes. The "pharmaceutically acceptable salts" include acid salts or basic salts; the acid salt comprises hydrochloride, sulfate, phosphate, citrate, hydrobromide, acetate, benzoate, benzenesulfonate, tartrate, carbonate, citrate, gluconate, lactate, malate, methanesulfonate, stearate, valerate or nitrate; the basic salt comprises sodium salt, calcium salt, potassium salt, zinc salt or meglumine salt. Preferably, the antibiotic comprises any one or a combination of at least two of amphotericin B, nystatin, miconazole, ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, flucytosine, terbinafine, caspofungin, micafungin, anidulafungin, griseofulvin, penicillin, amoxicillin, ampicillin, cefradine, cephalexin, ceftazidime, imipenem, amikacin, gentamicin, doxycycline, tetracycline, minocycline, erythromycin, clarithromycin, azithromycin, sulfadiazine, ciprofloxacin, levofloxacin, metronidazole, clindamycin or fosfomycin. Preferably, the fungus comprises any one or a combination of at least two of candida albicans, candida glabrata, candida tropicalis, candida krusei, aspergillus fumigatus, aspergillus niger, aspergillus flavus, aspergillus oryzae, fusarium, cryptococcus neoformans, candida, mucor, histoplasma capsulatum, cercospora, coccidioides, cryptococcus garteus, or paracoccidiosis. Preferabl