Durable multi-component antibiotic formulation for topical use
View Patent ↗Disclosed are methods and formulations for the treatment or prevention of infections on mammalian tissues such as skin. Specifically, the methods of this invention involve the in situ formation of a polymeric cyanoacrylate film containing mixed antibiotics over mammalian tissue.
1. A polymerizable film-forming cyanoacrylate composition comprising:
from about 50 to 99 weight percent of a polymerizable cyanoacrylate ester based on the total weight of the composition;
an antibacterially effective amount of an antibiotic or a mixture of antibiotics which are insoluble in the polymerizable cyanoacrylate ester; and
a sufficient amount of a thickening agent which forms a stable suspension or gel in combination with the cyanoacrylate ester and the antibiotic or the mixture of antibiotics, wherein at least 50% of the suspended material remains in suspension for a period of at least 3 months at 20° C.
2. The polymerizable film-forming cyanoacrylate composition according to claim 1 , wherein said composition is characterized as possessing thixotropic properties.
3. The polymerizable film-forming cyanoacrylate composition according to claim 2 , wherein at least 50% of the suspended material remains in suspension for a period of at least 6 months.
4. The polymerizable film-forming cyanoacrylate composition according to claim 3 , wherein at least 90% of the suspended material remains in suspension for a period of at least 6 months.
5. The polymerizable film-forming cyanoacrylate composition according to claim 1 , wherein a mixture of antibiotics is employed in said composition to provide a spectrum of antibacterial activity.
6. The polymerizable film-forming cyanoacrylate composition according to claim 1 , wherein said mixture of antibiotics comprises neomycin, polymixin B sulfate, and bacitracin.
7. The composition according to claim 1 , wherein said polymerizable cyanoacrylate ester composition comprises a cyanoacrylate ester, which in monomeric form, is represented by formula I:
where R is selected from the group consisting of:
alkyl of 1 to 10 carbon atoms,
alkenyl of 2 to 10 carbon atoms,
cycloalkyl groups of from 5 to 8 carbon atoms,
phenyl, 2-ethoxyethyl, 3-methoxybutyl, and
a substituent of the formula:
wherein each R′ is independently selected from the group consisting of:
hydrogen and methyl, and
R″ is selected from the group consisting of:
alkyl of from 1 to 6 carbon atoms,
alkenyl of from 2 to 6 carbon atoms,
alkynyl of from 2 to 6 carbon atoms,
cycloalkyl of from 3 to 8 carbon atoms,
aralkyl selected from the group consisting of benzyl, methylbenzyl and phenylethyl,
phenyl, and
phenyl substituted with 1 to 3 substituents selected from the group consisting of hydroxy, chloro, bromo, nitro, alkyl of 1 to 4 carbon atoms, and alkoxy of from 1 to 4 carbon atoms.
8. The composition according to claim 7 , wherein R is alkyl of from 2 to 10 carbon atoms.
9. The composition according to claim 8 , wherein R is alkyl of from 2 to 8 carbon atoms.
10. The composition according to claim 9 , wherein R is selected from the group consisting of butyl, pentyl or octyl.
11. The composition according to claim 10 , wherein R is n-butyl.
12. The composition according to claim 1 wherein said cyanoacrylate composition further comprises a biocompatible plasticizer.
13. The composition according to claim 12 , wherein said biocompatible plasticizer is dioctyl phthalate or acetyl tri-n-butyl citrate.
14. The composition according to claim 13 , wherein said cyanoacrylate adhesive composition further comprises a polymerization inhibitor.
15. The composition according to claim 14 , wherein said polymerization inhibitor is SO 2 .