Ionene polymers containing biologically-active anions

• US 5,575,993 A
• Filed: 08/31/1994
• Issued: 11/19/1996
• Est. Priority Date: 08/31/1994
• Status: Expired due to Term

• Current Assignee: Buckman Laboratories International, Inc (Bulab Holdings Incorporated)
• Original Assignee: Buckman Laboratories International, Inc (Bulab Holdings Incorporated)
• Inventors: Ward, James A., Del Corral, Fernando
• Primary Examiner(s): KRASS, FREDERICK F
• Application Number:
  US08/297,953
• Time in Patent Office: 811 Days
• Field of Search: 424/78.3, 424/78.37, 424/78.38, 424/78.1, 424/78.13, 424/78.15, 424/78.14, 424/329, 424/405, 514/252, 514/253, 514/316, 514/332, 514/357, 514/352, 514/396, 514/399, 514/400, 514/408, 514/406, 514/428, 514/424, 514/425, 514/422, 514/595, 514/596, 514/597, 514/598 , 514/426, 514/642, 514/588, 514/643, 71/27, 71/30, 422/6, 422/154, 422/155, 422/156, 422/7, 422/158, 422/159, 422/160, 422/16, 43/132.1, 504/345, 252/515 R, 252/82, 252/84, 252/301.35, 252/405
• US Class Current: 424/78.1
• CPC Class Codes: A01N 2300/00 Combinations or mixtures of active ingredients covered by classes A01N27/00 - A01N65/48 with other active or formulation relevant ingredients, e.g. specific carrier materials or surfactants, covered by classes A01N25/00 - A01N65/48
• CPC Class Codes: A01N 33/12 Quaternary ammonium compounds
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 8/347 Phenols
• CPC Class Codes: A61K 8/368 with carboxyl groups directly bound to carbon atoms of aromatic rings
• CPC Class Codes: A61K 8/411 Aromatic amines, i.e. where the amino group is directly linked to the aromatic nucleus
• CPC Class Codes: A61K 8/731 Cellulose; Quaternized cellulose derivatives
• CPC Class Codes: A61K 8/84 obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
• CPC Class Codes: A61P 17/16 Emollients or protectives, e.g. against radiation
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61Q 17/005 Antimicrobial preparations
• CPC Class Codes: A61Q 17/04 Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: A61Q 5/00 Preparations for care of the hair

Abstract

Ionene polymers having biologically-active organic and/or inorganic anions are described. Methods to prepare the ionene polymers, compositions containing them and their methods of use are also described.

Claims

1. A water-soluble ionene polymer of formula I:

##STR3## wherein n is an integer from 4 to 400 corresponding to the degree of polymerization of the polymer;

R₁, R₂, R₃ and R₄ represent the same or different substituent selected from the group consisting of hydrogen, a C₁ to C₁₆ alkyl group, a C₁ to C₁₆ alkyl group substituted with one or more hydroxyl groups, a benzyl group, and a benzyl group substituted with one or more C₁ to C₁₆ alkyl groups;

B represents a divalent C₂ to C₁₆ aliphatic hydrocarbon radical which can be substituted by hydroxyl, a divalent C₅ to C₉ cyclic hydrocarbon radical, a di-(C₂ to C₆)-alkylene ether, a phenylene or alkyl-substituted phenylene radical, or the divalent group R₁ R₂ NBNR₃ R₄ of formula I represents a divalent radical of the structure;

space="preserve" listing-type="equation">R.sub.1 R.sub.2 N--(CH.sub.2).sub.p --NR.sub.5 --C(O)--NR.sub.6 --(CH.sub.2).sub.p --NR.sub.3 R.sub.4

where p is an integer from 2 to 6, R₁, R₂, R₃ and R₄ are the same as defined above, and R₅ and R₆ are the same or different and are selected from the group consisting of hydrogen and a C₁ to C₁₆ alkyl group, or the divalent radical R₁ R₂ NBNR₃ R₄ forms a heterocyclic group selected from 1,2-pyrazolidinyl, 1,3-imidazolindiyl, 1,4-piperazindiyl, aminopyrrolidinyl, or aminopiperidiyl wherein the heterocyclic group may be substituted with one or more groups selected from a C₁ to C₆ alkyl group, a hydroxyl group, a halide, or a phenyl group;

A^- is an anion derived from a biologically-active compound having at least one acid functionality with the proviso that said anion is not a halide anion;

X^- is an anion derived from a mineral or organic acid; and

the degree of substitution of the polymer is from about 0.005 to 0.5.

2. An ionene polymer according to claim 1, wherein the anion A^- is derived from a herbicide.

3. An ionene polymer according to claim 2, wherein the herbicide is 2,4-dichlorophenoxyacetic acid.

4. An ionene polymer according to claim 1, wherein the anion A^- is derived from a disinfectant and the anion X^- is selected from the group consisting of halide ions.

5. An ionene polymer according to claim 4, wherein the disinfectant is selected from the group consisting of phenol and phenol derivatives.

6. An ionene polymer according to claim 1, wherein the anion A^- is derived from a pharmaceutical compound and the anion X^- is selected from the group consisting of halide ions.

7. An ionene polymer of claim 1, wherein

n is from 5-50;

R₁, R₂, R₃ and R₄ are each methyl, ethyl, or benzyl;

B is methylene, ethylene, propylene, 2-hydroxypropylene, butylene, isobutylene, diethylene ether, or phenylene; and

X^- is a halide.

8. An ionene polymer of claim 7, wherein

R₁, R₂, R₃ and R₄ are each methyl,

B is ethylene, and

X^- is chloride.

9. An ionene polymer of claim 1, wherein the group R₁ R₂ NBNR₃ R₄ is a radical of the structure:

space="preserve" listing-type="equation">R.sub.1 R.sub.2 N--(CH.sub.2).sub.p --NR.sub.5 --C(O)--NR.sub.6 --(CH.sub.2).sub.p --NR.sub.3 R.sub.4.

10. An ionene polymer of claim 9, wherein

n is from 5-50;

R₁, R₂, R₃ and R₄ are each methyl, ethyl or benzyl;

R₅ and R₆ are each methyl or ethyl;

p is 2 or 3; and

X^- is a halide.

11. An ionene polymer of claim 10, wherein R₁, R₂, R₃, R₄, R₅ and R₆ are methyl, p is 3, and X^- is a halide.

12. The ionene polymer of claim 1 wherein the anion A^- is I₃^-.

13. A method for the preparation of an ionene polymer of formula I according to claim 1, the method comprising the steps of:

reacting a protonated diamine of formula IV ##STR4## with an epihalohydrin under conditions sufficient to form an intermediate of formula VI ##STR5## and polymerizing said intermediate with a diamine of formula III ##STR6## under conditions sufficient to form said polymer.

14. A method of claim 13, further comprising, before said reaction step, the steps of

neutralizing a diamine of formula III with up to one equivalent of a biologically-active acid, HA, per amine group;

and

adding sufficient acid, HX, so that the total amount of acid used is approximately equivalent to the amine groups present, thereby forming the protonated diamine of formula IV.

15. A method according to claim 13, wherein the epihalohydrin is epichlorohydrin.

16. A method of claim 13, wherein the anion A^- is I₃^-.

17. A method of claim 13, wherein the anion A^- is a phenolate anion.

42. A method according to claim 14, wherein the biologically-active acid is the herbicide 2,4-dichlorophenoxyacetic acid.

43. A fertilizer comprising a polymer of claim 1 or 18.

44. A pesticide comprising a polymer of claim 1 or 18.

45. A therapeutic agent comprising a polymer of claim 1.

46. A dispersant comprising a polymer of claim 1 or 18.

47. A microbicide comprising a polymer of claim 1 or 18.

48. A preservative comprising a polymer of claim 1 or 18.

49. A disinfectant comprising a polymer of claim 1 or 18.

50. A plant growth regulator comprising a polymer of claim 1 or 18.

51. A sizing agent comprising a polymer of claim 1 or 18.

52. A surfactant comprising a polymer of claim 1 or 18.

53. A herbicide comprising a polymer of claim 1 or 18.

54. A sanitizer comprising a polymer of claim 1 or 18.

55. A scale control agent comprising a polymer of claim 1 or 18.

56. A fluorescent agent comprising a polymer of claim 1 or 18.

57. A termicide comprising a polymer of claim 1 or 18.

58. A method for fertilizing comprising applying to foliage the fertilizer of claim 43.

59. A method to destroy pests comprising applying to the pests or to the locus of the pests the fertilizer of claim 44.

60. A method for promoting the formation and stabilization of a dispersion of at least one substance in another substance comprising adding the dispersant of claim 46 to the dispersion.

61. A method to destroy microorganisms comprising applying to the microorganisms or to the locus of the microorganisms the microbicide of claim 47.

62. A method to preserve a substance comprising applying or adding to the substance the preservative of claim 48.

63. A method for disinfecting a substance comprising applying to the substance the disinfectant of claim 49.

64. A method to regulate plant growth comprising applying to the plant or to the locus of the plant the plant growth regulator of claim 50.

65. A method to destroy or inhibit plant growth comprising applying to a plant or to the locus of the plant the herbicide of claim 53.

66. A method of sanitizing a substance comprising cleaning or sterilizing the substance with the sanitizer of claim 54.

67. A method to destroy termites comprising applying to the termites or to the locus of the termites the termiticide of claim 57.

68. A method to treat udder infections in dairy cattle comprising administering a pharmaceutically effective amount of a formulation comprising the polymer of claim 1 or 18.

69. An algicide comprising a polymer of claim 1 or 18.

70. A method for disinfecting water comprising applying or adding to said water the algicide of claim 69.

71. A topical antiseptic comprising the polymer of claim 1 or 18.

18. A water-soluble ionene polymer of formula II:

##STR7## wherein n is an integer from 4 to 400 corresponding to the degree of polymerization of the polymer;

R₁, R₂, R₃ and R₄ represent the same or different substituent selected from the group consisting of hydrogen, a C₁ to C₁₆ alkyl group, a C₁ to C₁₆ alkyl group substituted with one or more hydroxyl groups, a benzyl group and a benzyl group substituted with one or more C₁ to C₁₆ alkyl groups;

B represents a divalent C₂ to C₁₆ aliphatic hydrocarbon radical which can be substituted by hydroxyl, a divalent C₅ to C₉ cyclic hydrocarbon radical, a di-(C² to C⁶)-alkylene ether, a phenylene or alkyl-substituted phenylene radical or the divalent group R₁ R₂ NBNR₃ R₄ of formula II represents a divalent radical of the structure;

space="preserve" listing-type="equation">R.sub.1 R.sub.2 N--(CH.sub.2).sub.p --NR.sub.5 --C(O)--NR.sub.6 --(CH.sub.2).sub.p --NR.sub.3 R.sub.4

where p is an integer from 2 to 6, R₁, R₂, R₃, and R₄ are the same as defined above, and R₅ and R₆ are the same or different and are selected from the group consisting of hydrogen and a C₁ to C₁₆ alkyl group, or the divalent radical R₁ R₂ NBNR₃ R₄ forms a heterocyclic group selected from 1,2-pyrazolidinyl, 1,3-imidazolindiyl, 1,4-piperazindiyl, aminopyrrolidinyl, or aminopiperidiyl wherein the heterocyclic group may be substituted with one or more groups selected from a C₁ to C₆ alkyl group, a hydroxyl group, a halide, or a phenyl group;

A^- is an anion derived from a biologically-active compound having at least one acid functionality with the proviso that said anion is not a halide anion;

X^- is an anion derived from a mineral or organic acid; and

the degree of substitution of the polymer is from about 0.005 to 0.333.

19. An ionene polymer according to claim 18, wherein the anion A^- is derived from a herbicide.

20. An ionene polymer according to claim 19, wherein the herbicide is 2,4-dichlorophenoxyacetic acid.

21. An ionene polymer according to claim 18, wherein the anion A^- is derived from a disinfectant and the anion X^- is selected from the group consisting of halide ions.

22. An ionene polymer according to claim 21, wherein the disinfectant is selected from the group consisting of phenol and phenol derivatives.

23. An ionene polymer according to claim 18, wherein the anion A^- is I₃^-.

24. An ionene polymer of claim 18, wherein,

n is from 5-50;

R₁, R₂, R₃ and R₄ are each methyl, ethyl, or benzyl;

B is methylene, ethylene, propylene, 2-hydroxypropylene, butylene, isobutylene, diethylene ether, or phenylene;

X^- is a halide.

25. An ionene polymer of claim 24, wherein,

R₁, R₂, R₃ and R₄ are each methyl,

B is ethylene, and

X^- is chloride.

26. An ionene polymer of claim 18, wherein the group R₁ R₂ NBNR₃ R₄ is a radical of the structure:

space="preserve" listing-type="equation">R.sub.1 R.sub.2 --(CH.sub.2).sub.p --NR.sub.5 --C(O)--NR.sub.6 --(CH.sub.2).sub.p --NR.sub.3 R.sub.4.

27. An ionene polymer of claim 26, wherein

n is from 5-50;

R₁, R₂, R₃ and R₄ are each methyl, ethyl or benzyl;

R₅ and R₆ are each hydrogen, methyl or ethyl;

p is 2 or 3; and

X^- is a halide.

28. An ionene polymer of claim 26, wherein R₁, R₂, R₃ and R₄ are methyl, R₅ and R₆ are hydrogen, p is 3, and X^- is a halide.

29. A method for the preparation of an ionene polymer of formula II according to claim 18, the method comprising the steps of:

reacting a protonated diamine of formula IV ##STR8## with an epihalohydrin under conditions sufficient to form an intermediate of formula VI ##STR9## and polymerizing said intermediate with a secondary amine of formula VII ##STR10## under conditions sufficient to form said polymer.

30. A method of claim 29, further comprising, before said reaction step, the steps of

neutralizing a diamine with up to one equivalent of a biologically-active acid, HA, per amine group;

and

adding sufficient acid, HX, so that the total amount of acid used is approximately equivalent to the amine groups present, thereby forming the protonated diamine of formula IV.

31. A method according to claim 29, wherein the epihalohydrin is epichlorohydrin.

32. A method according to claim 30, wherein the biologically-active acid is the herbicide 2,4-dichlorophenoxyacetic acid.

33. A method according to claim 30, wherein the anion A_- is a phenolate anion.

34. A method according to claim 29, wherein the anion A^- is I₃^-.

35. A method for the preparation of an ionene polymer having a biologically-active anion comprising the steps of

a) reacting a protonated diamine having at least one anion derived from a biologically-active compound, with the proviso that said anion is not a halide anion with an epihalohydrin, and

b) polymerizing the product of step a) with a secondary amine or a diamine.

36. A compound of formula VI:

##STR11## wherein R₁, R₂, R₃ and R₄ represent the same or different substituent selected from the group consisting of hydrogen, a C₁ to C₁₆ alkyl group, a C₁ to C₁₆ alkyl group substituted with one or more hydroxyl groups, a benzyl group and a benzyl group substituted with one or more C₁ to C₁₆ alkyl groups;

B represents a divalent C₂ to C₁₆ aliphatic hydrocarbon radical which can be substituted by hydroxyl, a divalent C₅ to C₉ cyclic hydrocarbon radical, a di-(C₂ to C₆)-alkylene ether, a phenylene or alkyl-substituted phenylene radical, or the divalent group R₁ R₂ NBNR₃ R₄ in formula VI represents a divalent radical of the structure;

space="preserve" listing-type="equation">R.sub.1 R.sub.2 N--(CH.sub.2).sub.p --NR.sub.5 --C(O)--NR.sub.6 --(CH.sub.2).sub.p --NR.sub.3 R.sub.4

where p is an integer from 2 to 6 and R₅ and R₆ are the same or different and selected from the group consisting of hydrogen and a C₁ to C₁₆ alkyl group, or the divalent radical R₁ R₂ NBNR₃ R₄ forms a heterocyclic group selected from 1,2-pyrazolidinyl, 1,3-imidazolindiyl, 1,4-piperazindiyl, aminopyrrolidinyl, or aminopiperidiyl wherein the heterocyclic group may be substituted with one or more groups selected from a C₁ to C₆ alkyl group, a hydroxyl group, a halide, or a phenyl group;

A^- is an anion derived from a biologically-active compound having at least one acid functionality with the proviso that said anion is not a halide anion; and

X^- is an anion derived from a mineral acid.

37. A compound of claim 36, wherein

n is from 5-50;

R₁, R₂, R₃, R₄ are each methyl, ethyl, or benzyl;

B is methylene, ethylene, propylene, 2-hydroxypropylene, butylene, isobutylene, diethylene ether, or phenylene; and

X^- is a halide.

38. A compound of claim 37, wherein;

R₁, R₂, R³, R₄ are each methyl,

B is ethylene, and

X^- is chloride.

39. A compound of claim 36, wherein the group R₁ R₂ NBNR₃ R₄ is a radical of the structure:

space="preserve" listing-type="equation">R.sub.1 R.sub.2 N--(CH.sub.2).sub.p --NR.sub.5 --C(O)--NR.sub.6 --(CH.sub.2).sub.p --NR.sub.3 R.sub.4.

40. A compound of claim 39, wherein

R₁, R₂, R₃ and R₄ are each methyl, ethyl or benzyl;

R₅ and R₆ are each hydrogen, methyl or ethyl;

p is 2 or 3; and

X^- is a halide.

41. A compound of claim 40, wherein R₁, R₂, R₃ and R₄ are methyl, R₅ and R₆ are hydrogen, p is 3, and X^- is a halide.