Antimicrobial compounds and compositions, and uses thereof
Inventors
Ala'Aldeen, Dlawer • Mahdavi, Jafar • Soultanas, Panos
Assignees
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Publication Number
US-9961886-B2
Publication Date
2018-05-08
Expiration Date
Abstract
A method of enhancing the growth of an animal is provided. The method includes causing the animal to ingest or absorb an effective amount of one or more Fe III complex compounds, including but not limited to Fe III complexes comprising ligands bound to the iron center selected from amino acids or α-hydroxy acids, o-hydroxy benzoic acids or pyridine-2-carboxylic acids, such as ferric quinate, ferric tyrosine, ferric DOPA and ferric phenylalanine. Compounds which are structural and/or functional variants, derivatives and/or analogs of the foregoing compounds, as further described herein are also disclosed. Methods for inhibiting, reducing, or preventing biofilm formation or buildup on a surface; the treatment of, inhibition of growth of, and inhibition of colonization by, bacteria, both in biological and non-biological environments; disinfecting surfaces, potentiating the effects of antibiotics and other anti-microbial agents, and increasing the sensitivity of bacteria and other microorganisms, to anti-microbial agents are also provided.
Core Innovation
The invention provides a method of treating microbial infection or colonization in an animal by administering, to the infected or at risk animal, a pharmaceutical or veterinary product, a medical device, or a dietary product comprising one or more compounds formed of iron complexed with alpha-amino acids selected from a defined group and present in L-form, D-form, or a mixture of D, L-forms. The compounds are identified as Fe-QA (ferric quinate), Fe-Tyr (ferric tyrosine), Fe-DOPA (ferric DOPA), and Fe-Phe (ferric phenylalanine), and the compound is the only ferric amino acid complex in the product or device.
The method is carried out in an amount effective to enhance growth and weight gain, and the invention is therefore focused on using the iron complexed with alpha-amino acids in formulations or devices to treat microbial infection or colonization while improving animal growth and weight gain. The document also links administration or use with improving feed utilization.
The document further describes microbial infection treatment through antibiotic potentiation and antibiotic resistance reversal, including increasing sensitivity to antibiotic resistance. It also describes targeting biofilm formation, including inhibiting, dispersing, removing, and preventing biofilm formation on biological and non-biological surfaces, including medical device and dental plaque contexts, and ties this to biofilm associated with cystic fibrosis and named organisms.
Claims Coverage
The independent claim centers on treating microbial infection or colonization in an animal with a product or device containing a defined iron alpha-amino acid complex as the only ferric amino acid complex. The claim coverage includes one main inventive concept, with dependent features refining antimicrobial combination, delivery routes, and biofilm-associated contexts.
Growth-enhancing treatment with only ferric alpha-amino acid iron complex
A method of treating microbial infection or colonization in an animal in an amount effective to enhance growth and weight gain by administering a pharmaceutical or veterinary product, a medical device, or a dietary product comprising one or more compounds formed of iron complexed with alpha-amino acids selected from alanine, aspartic acid, cysteine, methionine, glutamic acid, glycine, isoleucine, leucine, phenylalanine, proline, serine, threonine, tyrosine, and valine in L-form, D-form, or a mixture of D, L-forms, wherein the compound is the only ferric amino acid complex in the product or device.
Combination with specified antimicrobial agents
The method includes one or more antimicrobial agents and encompasses antibiotic potentiation.
Sub-therapeutic dosing relative to a non-receiving control
One or more antimicrobial agents are administered at an amount less than a therapeutically effective or therapeutically optimal dose to a patient or animal not receiving the product.
Treatment of infection or colonization with specified antibiotic-resistant microorganisms
The method includes infecting the animal with an antibiotic-resistant microorganism, including biofilm-forming bacteria.
Cystic fibrosis-associated biofilm context
The method is characterized in that the biofilm is associated with cystic fibrosis.
Overall, the claim coverage centers on administering a product or device containing a defined iron alpha-amino acid complex as the only ferric amino acid complex to treat microbial infection or colonization in an animal and enhance growth and weight gain, with dependent features addressing antimicrobial combination, antibiotic-resistant microorganisms, and cystic fibrosis-associated biofilm.
Stated Advantages
Enhancing growth and weight gain in the treated animal.
Improving feed utilization.
Potentiating antibiotics.
Reversing or increasing sensitivity to antibiotic resistance in antibiotic-resistant bacteria.
Inhibiting biofilm formation on biological and non-biological surfaces.
Dispersing, removing, and preventing biofilm formation.
Binding to Campylobacter major outer membrane proteins (MOMPs) and/or FlaA as a described mechanism for biofilm-related action.
Reduce Campylobacter carriage under dirty-litter challenge.
Prevent biofilm formation on human teeth.
Improve chicken growth.
Inhibit Pseudomonas aeruginosa biofilm formation on contact lenses.
Reduce growth of antibiotic-resistant EPEC when used with gentamicin.
Documented Applications
Treating microbial infection or colonization in an animal to enhance growth and weight gain.
Use for antibiotic potentiation and reversing or increasing sensitivity to antibiotic resistance in antibiotic-resistant bacteria via combination or in vivo formation with antibiotics.
Inhibiting, dispersing, removing, and preventing biofilm formation on biological and non-biological surfaces.
Biofilm inhibition in medical device and dental plaque contexts, including catheters, contact lenses, and human teeth.
Targeting Campylobacter major outer membrane proteins (MOMPs) and/or FlaA as part of biofilm-related activity.
Biofilm-associated infection context including cystic fibrosis-associated biofilm.
Treatment of microbial infection or colonization in animals, including chicken colonization with Campylobacter jejuni.
Reduction of EPEC growth when FeDOPA is used with gentamicin.
Inhibition of attachment or disruption of preformed biofilms using FeDOPA or FeTyr.
Inhibition of Campylobacter jejuni attachment/binding to histo-blood group antigens.
Inhibition of biofilm formation in plastic bead and surface attachment assays.
Inhibition of Helicobacter pylori attachment to human gastric tissue.
Sensitization of antibiotic-resistant strains to antibiotics, including kanamycin and gentamicin.
Use in formulation and delivery contexts including nebulizers and liposomes for cystic fibrosis, together with broader pharmaceutical or antimicrobial combinations.
Applying compounds using specified delivery routes, including oral, topical, buccal, dermal, transdermal, sublabial, and sublingual delivery, and optionally with dental products or chewable non-food items.
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