Polymeric antimicrobials and their use in pharmaceutical compositions

• US 5,300,287 A
• Filed: 11/04/1992
• Issued: 04/05/1994
• Est. Priority Date: 11/04/1992
• Status: Expired due to Fees

• Current Assignee: Alcon Manufacturing Limited (Alcon Incorporated)
• Original Assignee: Alcon Laboratories Incorporated (Alcon Incorporated)
• Inventors: Park, Joonsup
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Kulkosky, Peter F.
• Application Number:
  US07/971,424
• Time in Patent Office: 517 Days
• Field of Search: 424/405, 424/78.04, 424/78.35, 424/78.74, 528/422, 528/423, 528/424, 526/307.2, 526/304
• US Class Current: 424/78.04
• CPC Class Codes: A01N 33/12 Quaternary ammonium compounds
• CPC Class Codes: A01N 37/30 containing the groups —CO—N< and , both being directly attached by their carbon atoms to the same carbon skeleton, e.g. H2N—NH—CO—C6H4—COOCH3; Thio-analogues thereof
• CPC Class Codes: A61K 8/8158 Homopolymers or copolymers of amides or imides, e.g. (meth) acrylamide; Compositions of derivatives of such polymers
• CPC Class Codes: A61K 8/84 obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
• CPC Class Codes: A61L 12/145 Polymeric quaternary ammonium compounds
• CPC Class Codes: A61P 31/02 Local antiseptics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61Q 17/005 Antimicrobial preparations
• CPC Class Codes: C07D 207/46 with hetero atoms directly attached to the ring nitrogen atom
• CPC Class Codes: C08G 73/0206 Polyalkylene(poly)amines

Abstract

Novel polymeric antimicrobials having spacer moieties between amine and/or ammonium moieties have good antifungal activity. These compounds are useful in pharmaceutical and cosmetic compositions as preservatives and in contact lens care compositions as preservatives and/or disinfectants.

Claims

1. A random co-polymer of formula:

##STR6## and pharmaceutically acceptable salts thereof, wherein;

n and m can be the same or different and are;

integers between 1 and 10;

o+p=z, wherein z is the total number of structural units and z is a number between 3 and 10,000, and wherein o is a fraction of z between 0 and 100% and p is a fraction of z between 100 and 0%;

R¹ and R² can be the same or different and are selected from the group consisting of C₁ -C₅ alkyl;

B can be substituted or unsubstituted, branched or unbranched and is selected from the group consisting of;

C₁ -C₃₀ alkyl, C₁ -C₂₄ alkyl-substituted benzyl, C₃ -C₁₅ alkyl silane, and C₆ -C₁₅ cycloalkyl or arylalkyl; and

A can be substituted or unsubstituted, branched or unbranched and is selected from the group consisting of;

C₁ -C₂₀ alkyleneoxy.

2. The random co-polymer of claim 1, wherein:

n=m=2;

z is a number between 3 and 100;

R¹ =R² =C₁ -C₂ alkyl; and

B=substituted or unsubstituted, branched or unbranched C₁₂ C₁₈ alkyl.

3. The random co-polymer of claim 2, wherein:

n=m=2;

z is a number between 20 and 50;

R¹ =R² =CH₃ ;

B=substituted or unsubstituted, branched or unbranched C₁₄ alkyl; and

A=polyethyleneoxide succinate.

7. A pharmaceutical composition comprising an antimicrobially effective amount of a random co-polymer of claim 1.

8. The composition of claim 7, wherein the random copolymer of claim 1 is present at a concentration between about 0.00001 and about 1.0 wt %.

9. The composition of claim 8, wherein the random copolymer of claim 1 is present at a concentration between about 0.0005 and about 0.5 wt %.

10. The composition of claim 9, wherein the random copolymer of claim 1 is present at a concentration between about 0.001 and about 0.05 wt %.

11. The composition of claim 8, wherein the random copolymer of claim 1 is present at a concentration between about 0.00005 and about 0.05 wt %.

12. The composition of claim 11, wherein the random copolymer of claim 1 is present at a concentration between about 0.0001 and about 0.01 wt %.

19. A method of disinfecting a contact lens, comprising contacting a contact lens to a composition comprising a disinfecting amount of a random copolymer of claim 1 for a time sufficient to disinfect the lens.

20. The method of claim 19, wherein the random copolymer of claim 1 is present at a concentration between about 0.00001 and about 1.0 wt %.

4. A random co-polymer of formula:

##STR7## and pharmaceutically acceptable salts thereof, wherein;

A can be substituted or unsubstituted, branched or unbranched and is selected from the group consisting of;

C₁ -C₂₀ alkyleneoxy;

x+y=w, wherein w is the total number of structural units and w is a number between 3 and 1,000, and wherein x is a fraction of w between 0 and 100% and y is a fraction of w between 100 and 0%; and

n is an integer between 5 and 30.

5. The random co-polymer of claim 4, wherein:

w is a number between 3 and 100; and

n is an integer between 12 and 18.

6. The random co-polymer of claim 5, wherein:

A=polyethylene oxide;

w is a number between 20 and 50; and

n=14.

13. A pharmaceutical composition comprising an antimicrobially effective amount of a random copolymer of claim 4.

14. The composition of claim 13, wherein the random copolymer of claim 4 is present at a concentration between about 0.00001 and about 1.0 wt %.

15. The composition of claim 14, wherein the random copolymer of claim 4 is present at a concentration between about 0.0005 and about 0.5 wt %.

16. The composition of claim 15, wherein the random copolymer of claim 4 is present at a concentration between about 0.001 and about 0.05 wt %.

17. The composition of claim 14, wherein the random copolymer of claim 4 is present at a concentration between about 0.00005 and about 0.05 wt %.

18. The composition of claim 17, wherein the random copolymer of claim 4 is present at a concentration between about 0.0001 and about 0.01 wt %.

21. A method of disinfecting a contact lens, comprising contacting a contact lens to a composition comprising a disinfecting amount of a random copolymer of claim 4 for a time sufficient to disinfect the lens.

22. The method of claim 21, wherein the random copolymer of claim 4 is present at a concentration between about 0.00001 and about 1.0 wt %.