Medical item for prevention and treatment of ear infection

1. A method of treatment, said method comprising introducing a tympanostomy tube into a tympanic membrane, said tympanostomy tube formed from a molded composite comprising:

a) a melt blend of:

(i) an ethylene-vinyl acetate copolymer having a melt index less than 50 g/10 min. as measured by ASTM D1238 and comprising 10 to 50 percent by weight of vinyl acetate,

(ii) polyethylene glycol having a weight average molecular weight of from about 2,000 to about 20,000 Daltons; and

b) about 1 to about 30 percent by weight ciprofloxacin betaine dispersed throughout said melt blend forming said molded composite; said molded composite

comprising:

i) a first phase with said melt blend comprised of from about 0.1 to about 30 percent by weight of said ciprofloxacin betaine; and

ii) a second phase with said melt blend comprised of from about 95 to about 99.99 percent by weight of said ciprofloxacin betaine; and

iii) a third phase comprising undissolved ciprofloxacin betaine; and

wherein said molded composite provides a release of said ciprofloxacin betaine to a surrounding fluid over a time period of at least 30 days.

2. The method of claim 1 , wherein said ciprofloxacin betaine before dispersion in said melt blend has a cumulative particle size distribution described by the following Weibull distribution:

F

=

1

-

e

-

(

d

D

)

S

;

where:

d is the particle size, microns;

e is the base of natural logarithms equal to 2.71828 approximately;

F is the cumulative size fraction of particles smaller than d;

D is a characteristic size for the distribution, microns;

S is a shape factor for the distribution;

said distribution having a characteristic size of from about 5 to about 100 micrometers and a shape factor from about 1.1 to about 5, with an index of determination upon regression of at least about 0.90;

said index of determination being higher than obtained by regression of particle size against any of: a normal distribution, a log normal distribution, an exponential distribution, or an extreme value distribution.

3. The method of claim 1 or 2 wherein said composite comprises one or more bioactive agents additional to the ciprofloxacin betaine selected from the group consisting of carbapenems, cephalosporins, penicillins, lincosamides, tetracyclines, macrolides, glycopeptides, quinolones, oxazolidinones, aminoglycosides, gyrase inhibitors, and their combination.

4. The method of claim 1 , wherein said composite further comprises a bioactive anti-inflammatory agent.

5. The method of claim 3 , wherein a compression molded disk of said composite when placed in contact with a brain heart infusion broth having 1×10 5 per mL of bioluminescent Pseudomonas aeruginosa Xen 4 and incubated at 37° C., 5% CO 2 with 50 rpm orbital shaking, after rinsing to remove loosely adhered cells, shows less adhered biofilm than a control disk not containing ciprofloxacin but of otherwise the same composition and identically treated.

6. The method of claim 3 , wherein said one or more bioactive agents additional to the ciprofloxacin betaine is selected from the group consisting of meropenem, ceftazidime, amoxicillin, clindamycin, tetracycline, erythromycin, vancomycin, ciprofloxacin hydrochloride, linezolid, usnic acid, sodium usnate, polyhexamethylene biguanide, and their combination.

7. The method of claim 1 , wherein said ciprofloxacin betaine and said melt blend are subjected to a temperature sufficient to keep the melt blend as a melt and shear for at least about 1 minute to form the phases.

8. The method of claim 1 , wherein the molded composite comprises about 1 to about 25 percent by weight of the ciprofloxacin betaine.

9. A method of reducing biofilm formation, said method comprising introducing a tympanostomy tube into a tympanic membrane, said tympanostomy tube formed from a molded composite comprising:

a) a melt blend of:

(i) an ethylene-vinyl acetate copolymer having a melt index less than 50 g/10 min. as measured by ASTM D1238 and comprising 10 to 50 percent by weight of vinyl acetate,

(ii) polyethylene glycol having a weight average molecular weight of from about 2,000 to about 20,000 Daltons; and

b) about 1 to about 30 percent by weight ciprofloxacin betaine dispersed throughout said melt blend forming said molded composite; said molded composite

comprising:

i) a first phase with said melt blend comprised of from about 0.1 to about 30 percent by weight of said ciprofloxacin betaine; and

ii) a second phase with said melt blend comprised of from about 95 to about 99.99 percent by weight of said ciprofloxacin betaine; and

iii) a third phase comprising undissolved ciprofloxacin betaine; and

wherein said molded composite provides a release of said ciprofloxacin betaine to a surrounding fluid over a time period of at least 30 days.

10. The method of reducing biofilm formation as in claim 9 , wherein said ciprofloxacin betaine before dispersion in said melt blend has a cumulative particle size distribution described by the following Weibull distribution

F

=

1

-

e

-

(

d

D

)

S

;

where:

d is the particle size, microns;

e is the base of natural logarithms equal to 2.71828 approximately;

F is the cumulative size fraction of particles smaller than d;

D is a characteristic size for the distribution, microns;

S is a shape factor for the distribution;

said distribution having a characteristic size of from about 5 to about 100 micrometers and a shape factor from about 1.1 to about 5, with an index of determination upon regression of at least about 0.90;

said index of determination being higher than obtained by regression of particle size against any of: a normal distribution, a log normal distribution, an exponential distribution, or an extreme value distribution.

11. The method of reducing biofilm formation as in claim 9 or 10 wherein said composite comprises one or more bioactive antibiotics additional to the ciprofloxacin betaine selected from the group consisting of carbapenems, cephalosporins, penicillins, lincosamides, tetracyclines, macrolides, glycopeptides, quinolones, oxazolidinones, aminoglycosides, gyrase inhibitors, and their combination.

12. The method of reducing biofilm formation as in claim 9 or 10 , wherein a compression molded disk of said composite when placed in contact with a brain heart infusion broth having 1×10 5 per mL of bioluminescent Pseudomonas aeruginosa Xen 4 and incubated at 37° C., 5% CO 2 with 50 rpm orbital shaking for periods of 1 to 35 days, after rinsing to remove loosely adhered cells, shows less adhered biofilm than a control disk not containing ciprofloxacin but of otherwise the same composition and identically treated.

13. The method of reducing biofilm formation as in claim 9 or 10 , wherein said composite includes a bioactive anti-inflammatory agent.

14. The method of reducing biofilm formation as described in claim 11 , wherein said one or more bioactive antibiotics additional to the ciprofloxacin betaine is selected from the group consisting of beta lactam, meropenem, ceftazidime, amoxicillin, clindamycin, tetracycline, erythromycin, vancomycin, ciprofloxacin hydrochloride, linezolid, usnic acid, sodium usnate, polyhexamethylene biguanide, and their combination.

15. The method of reducing biofilm formation as in claim 9 , wherein said ciprofloxacin betaine and said melt blend are subjected to a temperature sufficient to keep the melt blend as a melt and shear for at least about 1 minute to form the phases.

16. The method of reducing biofilm formation as in claim 9 , wherein the molded composite comprises about 1 to about 25 percent by weight of the ciprofloxacin betaine.