Small Molecule Agents, Compositions, and Formulations, for Internal Use, Displaying Inhibitory Activity Against Gram-positive and/or Gram-negative Organisms

Abstract

Active components comprising lauric acid, or a lauric acid derivative, are utilized independently, or in combination, to provide new and useful compositions for bacteriostatic action against susceptible pathogens. The lauric acid derivative includes one or more of 12-aminododecanoic acid, 12-amino-1-dodecanoic acid methyl ester, sucrose monolaurate, 12-(7-nitrobenzofurazan-4-ylamino) dodecanoic acid, 4-nitrophenyl dodecanoate, 1-lauroyl-rac-glycerol, 3-oxo-N-(2-oxocyclohexyl) dodecanamide, butyl laurate, benzyl laurate, isoamyl laurate, monolaurin, isopropyl laurate, pentyl laurate, and hexyl laurate. A preparation includes combining the active component with lecithin, and after an initial processing phase, coating with chitosan or a carrier. Final compositions may be or may contain particles, such as nanoparticles. Final compositions, or formulations containing said final compositions, may be utilized internally, causing one or more membrane changes (e.g., a membrane of an internal target pathogen, which may or may not be an antibiotic-resistant pathogen). At least some compositions inhibit growth of one or more Gram-positive bacterial species and one or more Gram-negative bacterial species.

1 . A composition having broad spectrum antimicrobial action comprising:
 a lauric acid derivative as an active component of the composition, the lauric acid derivative being one of a strongly hydrophobic 12-carbon chain fatty acid and a strongly hydrophobic 12-carbon chain fatty acid ester, each having one or more carbon-containing side chains, in which each lauric acid derivative also has a partition coefficient, P, and to be strongly hydrophobic its log P value will be less than 4; and   lecithin components containing phospholipids and at least one bulky fatty acid having a carbon chain length from between about 14 and 20, and in an amount up to about 50 wt. % of the composition,   wherein the composition is in a form of nanoparticles, and is suitable for utilization in a formulation, the formulation as pharmacotherapy for a subject in need of a broad spectrum antimicrobial, having growth inhibitory action against more than one species of susceptible pathogenic microorganisms, and capable of having antimicrobial action against one or more susceptible Gram-positive bacteria and one or more susceptible Gram-negative bacteria.   
     
     
         2 . The composition of  claim 1 , wherein the lauric acid derivative is in an amount between about 0.001 wt. % and 30 wt. % of the composition, and is selected as one or more from a group consisting of 12-aminododecanoic acid, 12-amino-1-dodecanoic acid methyl ester, sucrose monolaurate, 12-(7-nitrobenzofurazan-4-ylamino) dodecanoic acid, 4-nitrophenyl dodecanoate, 1-lauroyl-rac-glycerol, 3-oxo-N-(2-oxocyclohexyl) dodecanamide, butyl laurate, benzyl laurate, isoamyl laurate, monolaurin, isopropyl laurate, pentyl laurate, hexyl laurate, and combinations thereof. 
     
     
         3 . The composition of  claim 1 , wherein the lecithin components are in an amount up to about 10 wt. % of the composition. 
     
     
         4 . The composition of  claim 1 , wherein the lecithin components are in an amount up to about 30 wt. % of the composition, and wherein the lecithin components are any one or more of; naturally occurring lecithin components; predominantly phosphatidylcholine; phospholipids and glycophospholipids; and a mixture of phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidic acid, phosphatidylserine, with or without lysophospholipids. 
     
     
         5 . The composition of  claim 1 , wherein the composition further comprises glycol chitosan in an amount up to about 10 wt. % of the composition. 
     
     
         6 . The composition of  claim 1 , wherein the composition further comprises a sufficient amount of one or more excipients forming the formulation. 
     
     
         7 . The composition of  claim 1 , wherein the composition is a suspension comprising the nanoparticles. 
     
     
         8 . The composition of  claim 1 , wherein the composition is in a dry or powder form comprising the nanoparticles. 
     
     
         9 . The composition of  claim 1 , wherein the composition further comprises glycol chitosan on an outer portion of the nanoparticles. 
     
     
         10 . A method of making a composition, the composition having broad spectrum antimicrobial action, the method comprising:
 suspending at least one of a lauric acid derivative with an evaporatable organic solvent having a low VOC to form a suspension, the lauric acid derivative being one of a strongly hydrophobic 12-carbon chain fatty acid and a strongly hydrophobic 12-carbon chain fatty acid ester, each having one or more carbon-containing side chains, in which each lauric acid derivative also has a partition coefficient, P, and to be strongly hydrophobic its log P value will be less than 4;   mixing the suspension with water;   combining the suspension with lecithin components containing a mixture of phospholipids and at least one bulky fatty acid having a carbon chain length from between about 14 and 20 to form a mixture, the lecithin components in an alkaline solution; and   sonicating and then filtering the mixture, thereby obtaining a composition containing nanoparticles, the composition containing the nanoparticles being suitable for use in a formulation, the formulation as pharmacotherapy for a subject in need of a broad spectrum antimicrobial, having growth inhibitory action against more than one species of susceptible pathogenic microorganisms and capable of having antimicrobial action against one or more Gram positive bacteria and one or more Gram-negative bacteria.   
     
     
         11 . The method of  claim 10 , wherein growth of the susceptible pathogenic microorganism, when exposed to the composition, is inhibited by the composition. 
     
     
         12 . The method of  claim 10  wherein combining the suspension with the lecithin components further comprises including a chitosan, the chitosan being in a same solution as the lecithin components, thereby, after sonicating, providing a composition containing chitosan coated nanoparticles, the composition containing the chitosan coated nanoparticles being suitable for a formulation for pharmacotherapy for a subject in need of a broad spectrum antimicrobial. 
     
     
         13 . A nanoparticle composition having broad spectrum antimicrobial action, the nanoparticle composition comprising at least three characteristics selected from a group comprising: (i) being one of a strongly hydrophobic 12-carbon chain fatty acid or a strongly hydrophobic 12-carbon chain fatty acid ester as an active component of the composition; (ii) having a carbon-containing a side chain on the active component, and (iii) each active component also having a partition coefficient, P, and to be strongly hydrophobic, a Log P value of the active component must be calculated and less than 4,
 wherein the nanoparticle composition is suitable for utilization in a formulation, the formulation as pharmacotherapy for a subject in need of a broad spectrum antimicrobial.   
     
     
         14 . The nanoparticle composition of  claim 13 , wherein the nanoparticle composition further comprises lecithin components containing a mixture of phospholipids and at least one bulky fatty acid having a carbon chain length from between about 14 and 20, and in an amount up to about 50 wt. % of the composition. 
     
     
         15 . The nanoparticle composition of  claim 13 , wherein the nanoparticle composition is formulated as an antimicrobial, and exhibits inhibitory growth activity against more than one susceptible pathogen, and, as an antimicrobial, it is capable of having antimicrobial action against one or more susceptible Gram-negative bacteria and one or more susceptible Gram-positive bacteria. 
     
     
         16 . The nanoparticle composition of  claim 13 , wherein the subject has or is suspected of having one or more susceptible Gram-negative bacteria from a group consisting of Enterobacteriaceae,  Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, Campylobacter, Shigella  spp, and combinations thereof. 
     
     
         17 . The nanoparticle composition of  claim 13 , wherein the subject has or is suspected of having one or more susceptible Gram-positive bacteria from a group consisting of  Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Chlostridium difficile, Mycobacterium  spp., Group A  Streptococcus , and Group B  Streptococcus.    
     
     
         18 . The nanoparticle composition of  claim 13 , wherein the nanoparticle composition further comprises lecithin components containing a mixture of phospholipids and at least one bulky fatty acid having a carbon chain length from between about 14 and 20, and in an amount up to about 50 wt. % of the composition, the lecithin components being selected as one or more from a group consisting of 12-aminododecanoic acid, 12-amino-1-dodecanoic acid methyl ester, sucrose monolaurate, 12-(7-nitrobenzofurazan-4-ylamino) dodecanoic acid, 4-nitrophenyl dodecanoate, 1-lauroyl-rac-glycerol, 3-oxo-N-(2-oxocyclohexyl) dodecanamide, butyl laurate, benzyl laurate, isoamyl laurate, monolaurin, isopropyl laurate, pentyl laurate, hexyl laurate, and combinations thereof. 
     
     
         19 . The nanoparticle composition of  claim 13 , wherein the nanoparticle composition further comprises: (i) lecithin components in an amount up to about 30 wt. % of the composition and containing a mixture of phospholipids and at least one bulky fatty acid having a carbon chain length from between about 14 and 20; and (ii) chitosan in an amount up to about 10 wt. % of the nanoparticle composition. 
     
     
         20 . The nanoparticle composition of  claim 14 , wherein the active component is selected as one or more from a group consisting of 12-aminododecanoic acid, 12-amino-1-dodecanoic acid methyl ester, sucrose monolaurate, 12-(7-nitrobenzofurazan-4-ylamino) dodecanoic acid, 4-nitrophenyl dodecanoate, 1-lauroyl-rac-glycerol, 3-oxo-N-(2-oxocyclohexyl) dodecanamide, butyl laurate, benzyl laurate, isoamyl laurate, monolaurin, isopropyl laurate, pentyl laurate, hexyl laurate, and combinations thereof, the active component being in an amount up to about 30 wt. % of the nanoparticle composition.