Combination of antimicrobial peptides and antibiotic drugs for treating diseases
Inventors
BACHNOFF, Niv • COHEN-KUTNER, Moshe
Assignees
Publication Number
US-10745452-B2
Publication Date
2020-08-18
Expiration Date
2037-08-07
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Abstract
The invention provides a peptide comprising: a core amino acid sequence, which is identical or similar to the amino acid sequence of a member of the Cecropin family in a combination with an antibiotic drug.The invention further provides methods of treating an infection, overcoming inherent or acquired resistance of a microorganism to an antibiotic agent or disinfecting a wound, the methods comprises administering the peptide in combination with the antibiotic drug to a subject in need thereof, wherein the peptide and the antibiotic drug are administered simultaneously or consecutively.
Core Innovation
The invention provides peptides comprising a core amino acid sequence identical or similar to members of the Cecropin family, extended at the N-terminus and/or C-terminus by groups capable of forming covalent bonds to create cyclic peptides or homomultimer assemblies. These peptides are administered in combination with antibiotic drugs, either simultaneously or consecutively, to treat infections, overcome inherent or acquired resistance of microorganisms to antibiotics, or disinfect wounds.
The problem addressed by the invention is the emergence of antibiotic-resistant microorganisms, which are no longer susceptible to currently available antimicrobial drugs, limiting the effectiveness of conventional antibiotic treatments. The invention seeks to restore or enhance antibiotic efficacy by combining antibiotic drugs with Cecropin family-based antimicrobial peptides that can increase antibiotic influx into bacterial cells, overcome resistance mechanisms such as drug efflux pumps, and result in synergistic antimicrobial effects.
Claims Coverage
The claims include three main inventive features focused on methods and compositions involving a specific cyclic peptide combined with antibiotic drugs.
Method of overcoming resistance and treating infection with cyclic peptide and antibiotic drug
Administering to a subject a combination of a cyclic peptide as set forth in SEQ ID No. 6 and an antibiotic drug to overcome inherent or acquired resistance of a microorganism to the antibiotic or to treat an infection. The administration may be simultaneous or consecutive.
Method of disinfecting wounds with cyclic peptide and antibiotic drug
Contacting a wound with a combination of a cyclic peptide as set forth in SEQ ID No. 6 and an antibiotic drug, where the wound may be selected from various types including blister, soft tissue, surgical, burn, ulcers, oral infections, and others.
Pharmaceutical composition combining cyclic peptide and antibiotic drug
A pharmaceutical composition comprising a combination of a cyclic peptide as set forth in SEQ ID No. 6 and an antibiotic drug, wherein the antibiotic drug may be selected from groups including Aminoglycoside, Ansamycin, Glycopeptide, Lincosamide, Macrolide, Monobactam, Nitrofuran, Oxazolidinone, Quinolone/Fluoroquinolone, Sulfonamide, and Tetracycline.
The claims cover methods of using a defined cyclic peptide combined with antibiotic drugs to overcome antibiotic resistance, treat infections, disinfect wounds, and pharmaceutical compositions comprising these combinations with a broad range of antibiotic classes.
Stated Advantages
Combination treatment can lower the effective doses of both antibiotic drugs and antimicrobial peptides needed to inhibit bacterial growth.
Peptides restore the susceptibility of antibiotic-resistant bacteria to drugs that are no longer effective when used alone.
The combination can produce a synergistic antimicrobial effect stronger than treatment with either the peptide or antibiotic drug alone.
Cyclic peptides exhibit higher stability while maintaining or improving biological activity.
Documented Applications
Treating infections caused by antibiotic-resistant bacteria including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella serotype Typhi, Acinetobacter baumannii, and other Enterobacteriaceae spp., Pseudomonas spp., Salmonella spp., or Acinetobacter spp.
Disinfecting wounds of various types such as blister wounds, soft tissue wounds, cutaneous abscesses, surgical wounds, sutured or contaminated lacerations, burn wounds, decubitus ulcers, stasis ulcers, leg ulcers, foot ulcers, venous ulcers, diabetic ulcers, ischemic ulcers, pressure ulcers, oral infections, periodontal diseases, and both partial and full thickness burns.
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