Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – C-o-group doai
Reexamination Certificate
1998-06-22
2001-11-20
Woodward, Michael P. (Department: 1631)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
C-o-group doai
C514S675000, C514S724000, C568S875000
Reexamination Certificate
active
06319958
ABSTRACT:
CROSS-REFERENCE TO RELATED APPLICATION
Not applicable.
BACKGROUND OF THE INVENTION
Microbial Resistance
Increasing incidence of microbial resistance to antibiotics and other antimicrobials is a growing concern facing the medical, food and sanitation industries. Major mechanisms of microbial resistance include active drug efflux systems and mutations which lead to nonspecific decreases in cell permeability. Other routes to resistance include antimicrobial degradation, inactivation by enzymatic modifications, or alteration of the drug's target within the cell (Nikkaido, 1994).
To counter the increasing incidence of antimicrobial resistance, the pharmaceutical and other industries have invested substantial resources in the search for new inhibitory compounds of microbial, plant and animal origin. Newer strategies to overcome antimicrobial resistance have included increased production of new synthetic and semisynthetic antibiotics which are resistant to the activities of those microbial enzymes (i.e. &bgr;-lactamases) capable of degradation or modification of naturally-derived antibiotics (Nikkaido, 1994).
Although many specific mechanisms of microbial resistance have been successfully addressed, it is thought that the more general mechanisms of altered permeability and increased efflux capability will become increasingly important from a clinical perspective (Nikkaido, 1994).
Efflux systems and mechanisms of antibiotic degradation rely on saturable biological structures (i.e., pumps or enzymes). If the nonspecific influx of an intracellularly or membrane-targeted lethal agent is high enough to overcome these inactivation mechanisms, then the effect of these mechanisms might be minimized, leading to the death of the cell.
Terpenoids
Terpenoids, a broad class of lipophilic secondary metabolites derived from mevalonate and isopentenyl pyrophosphate, occur widely in nature and have been of historical interest to man primarily for their contribution to the characteristic flavors and aromas of herbs, spices and flowers. As of 1991, the number of recognized natural terpenoids had reached an estimated 15,000 to 20,000 (Harborne, 1991).
Sesquiterpenoid compounds, containing 15 carbons, are formed biosynthetically from three 5-carbon isoprene units. Because of their naturally pleasing odors and flavors, many sesquiterpenoids of plant origin have found use in perfumery and flavoring applications and are now produced industrially from monoterpenoid feedstock. For example, nerolidol, commonly used to provide a base note for floral aroma compositions, is readily produced from linalool, itself derived from &agr;-pinene, which occurs in high concentration in turpentine oil (Bauer, et al., 1997).
Apart from their use in perfumery, terpenoids have been associated with a variety of important biological functions as pheromones, insect antifeedants, phytoalexins and others (Harborne, 1991).
BRIEF SUMMARY OF THE INVENTION
In one embodiment, the present invention is a method of promoting the uptake of exogenous antimicrobial compounds by microbial cells. The method comprises the step of exposing the microbial cell to an amount of a sesquiterpenoid effective to enhance antimicrobial compound uptake in the microorganism and an antimicrobial compound. In a preferred embodiment of the present invention the antimicrobial compound is an antibiotic. Most preferably, the antibiotic is selected from the group consisting of clindamycin, ciprofloxacin, erythromycin, tetracycline, gentamicin, vancomycin and polymyxin B sulfate.
In one embodiment of the present invention, the method involves a topical application of the sesquiterpenoid and antimicrobial compound to human or animal skin. For example, one might apply a cream or ointment comprising the sesquiterpenoid and antimicrobial compound to a wound.
In another embodiment, the present invention is the application of the sesquiterpenoid and antimicrobial compound to a hard or soft surface, such as a food, sink, sponge or bathroom fixture.
In a preferred embodiment of the present invention, the sesquiterpenoid is selected from the group consisting of farnesol, nerolidol, bisabolol and apritone. In a most preferred form of the invention, the sesquiterpenoid is either nerolidol or farnesol.
In one form of the present invention, the sesquiterpenoid is a mixture of different sesquiterpenoids.
The present invention is also an antimicrobial compound comprising an effective amount of a sesquiterpenoid and an antimicrobial compound. In a preferred form of this embodiment of the present invention, the antimicrobial compound is an antibiotic or food grade antimicrobial.
It is an object of the present invention to provide a method of sensitizing microorganisms, such as bacteria and fungi, to antimicrobials. By means of the present invention, microorganisms will become sensitive to an antibiotic or other antimicrobial compound at dosages previously thought to be ineffective.
Other advantages, features and objects of the present invention will become apparent after one has reviewed the specification, claims and drawings.
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Brehm-Stecher Byron F.
Johnson Eric A.
Borin Michael
Quarles & Brady LLP
Wisconsin Alumni Research Foundation
Woodward Michael P.
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