Use of bis-amines to enhance the antimicrobial activity of aqueous compositions
View Patent ↗The use of bis-amines to enhance the antimicrobial activity of pharmaceutical compositions is described. The bis-amines are particularly useful for enhancing the antimicrobial activity of aqueous ophthalmic compositions, such as artificial tears or ocular lubricants, and solutions for disinfecting contact lenses.
1. A sterile aqueous ophthalmic composition comprising a bis-amine of the following formula, in an amount effective to enhance the antimicrobial activity of the composition:
wherein:
R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are independently selected from the group consisting of:
H; —CH 2 OH; and C 1 -C 5 straight or branched alkyl or alkenyl, optionally containing one or more heteroatoms, provided that no more than one of R1, R2 and R3 is —CH 2 OH, and no more than one of R4, R5 and R6 is —CH 2 OH; and
X is (—CH 2 —) w CHOH—CHOH(—CH 2 —) w , wherein w is a whole number of from 1 to 6 and the hydroxy groups are in either cis or trans configurations;
or a pharmaceutically acceptable salt thereof, said composition having a physiologically compatible pH and an osmolality of 210 to 320 mOsm/kg.
2. A composition according to claim 1 , wherein the bis-amine of formula (I) is 1,4-bis[isobutylamino]2,3-dihydroxy butane.
3. A method of enhancing the antimicrobial activity of a sterile, aqueous pharmaceutical composition, which comprises including an effective amount of a bis-amine in the composition, said bis-amine having the formula:
wherein:
R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are independently selected from the group consisting of:
H; —CH 2 OH; and C 1 -C 5 straight or branched alkyl or alkenyl, optionally containing one or more heteroatoms, provided that no more than one of R1, R2 and R3 is —CH 2 OH, and no more than one of R4, R5 and R6 is —CH 2 OH; and
X is (—CH 2 ) w —CHOH—CHOH(—CH 2 —) w , wherein w is a whole number of from 1 to 6 and the hydroxy groups are in either cis or trans configurations;
or a pharmaceutically acceptable salt thereof.
4. A method according to claim 3 , wherein the bis-amine of formula (I) is 1,4-bis[isobutylamino]2,3-dihydroxy butane.
5. The composition of claim 1 further comprising a borate.
6. The method of claim 3 wherein the composition further comprises a borate.
7. The composition of claim 1 further comprising at least one additional antimicrobial activity enhancing agent.
8. The composition of claim 7 , wherein the at least one additional antimicrobial activity enhancing agent is either an amidoamine or an amino alcohol.
9. The composition of claim 7 , wherein the at least one additional antimicrobial activity enhancing agent is selected from the group consisting of myristamidopropyl dimethylamine and 2-amino-2-methyl-1-propanol.
10. The method of claim 3 wherein the composition further comprises at least one additional antimicrobial activity enhancing agent.
11. The method of claim 10 , wherein the at least one additional antimicrobial activity enhancing agent is either an amidoamine or an amino alcohol.
12. The method of claim 10 , wherein the at least one additional antimicrobial activity enhancing agent is selected from the group consisting of myristamidopropyl dimethylamine and 2-amino-2-methyl-1-propanol.
13. The composition of claim 1 further comprising at least one antimicrobial agent.
14. The composition of claim 13 , wherein the at least one antimicrobial agent is selected from the group consisting of polyquaternium-1 and polyhexamethylene biguanide.
15. The method of claim 3 , wherein the composition further comprises at least one antimicrobial agent.
16. The method of claim 15 , wherein the at least one antimicrobial agent is selected from the group consisting of polyquaternium-1 and polyhexamethylene biguanide.