Compositions and methods of use thereof
a technology of digestive system and composition, applied in the direction of drug composition, immunologic disorders, antibacterial agents, etc., can solve the problems of drug resistance, drug resistance, and difficulty in penetrating dense biofilms and mucus, so as to reduce pulmonary fibrosis, improve lung function, and increase the accessibility of other therapeutic agents
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example 1
ction of Biofilms Compared to Relevant Mucolytics
Protocol:
[0258]Three Methicillin-resistant staphalococcus aureas (MRSA) clinical isolates were obtained from Providence Medical Center (Portland, Oreg.) and had been obtained from respiratory tract / sputum (SA4, SA5, and SA6). P. aeruginosa strains SUS116 and MR29 (clinical isolates from Jane Burns Lab Seattle Childrens Hospital, WA), and Burkholderia cepacia (ATCC 25416), were obtained from a −80 C freezer stock culture and propagated overnight in nutrient broth at 37° C. The optical density (OD) of each culture was measured at 600 nm, and each culture was normalized to 2 McFarland (0.451 OD), using tryptic soy broth (TSB). The cultures were diluted in TSB supplemented with 1% glucose to obtain a cell density of 2.0×107 cells / mL. Each culture was mixed well by inversion and passed on to a flat-bottomed 96-well plate by placing 200 μL into each well, corresponding to approximately 4.0×106 bacteria / well. The bacteria formed static biofi...
example 2
Polyols Synergistic Reduction of MRSA Biofilms
Protocol:
[0261]The clinical isolates (MRSA SA5, P. aeruginosa SUS116), and B. cepacia (ATCC 25416) were obtained from a −80 C freezer stock culture and propagated overnight in nutrient broth at 37° C. The OD of each culture was measured at 600 nm, and each culture was normalized to 2 McFarland (0.451 OD), using TSB. The cultures were diluted in TSB supplemented with 1% glucose to obtain a cell density of 2.0×107 cells / mL. Each culture was mixed by inversion and 200 μL was placed on to a flat-bottomed 96-well, corresponding to approximately 4.0×106 bacteria / well. The bacteria formed static biofilms at 37° C. for approximately 20 hours.
[0262]After incubation, the biofilms were washed twice allowing only adherent biofilm to remain on the plate. Each isolate was then treated for 1 hour in a 37° C. incubator with 200 μl of 600 μg / ml PAAG (22.4% functionalization, 36.9 kDa, 89.74 DDA, 1.63 PDI), 400 μg / ml PAAG, 200 μg / ml PAAG, 100 μg / ml PAAG, ...
example 6
Protocol:
[0279]Initial studies used the MBEC™ system to determine optimized PAAG (30.7% functionalization, 86.53 kDa, 87.92 DDA, 1.63 PDI) treatment time, administration, and dose for biofilm disruption of methicillin resistant Staphylococcus aureus (MRSA). Treatments showed the difference of multiple short-term rinses to 1-hour treatment against 24-hour MRSA biofilms.
Results:
[0280]PAAG was able to significantly reduce the viable bacteria associated with the biofilm. When PAAG was used to treat S. aureus a 2-minute rinse, three times a day was shown to be better or as effective as a single one-hour treatment with PAAG at 250 or 500 μg / mL (FIG. 16). These comparative studies demonstrate that a brief treatment, three times daily, was effective at reducing MRSA biofilms and may be a feasible dosing schedule for use in patients.
Protocol:
[0281]The biofilms were grown according to MBEC™ on a peg lid for 48 hours. The pegs were rinsed and placed into a 96-well pla...
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