Method of preparing antimicrobial composition

Abstract

To provide a method for preparing new stable liquid, non-particulate formulations of metal ions which are easy to incorporate into or apply onto materials and can achieve sustained antimicrobial efficacy.SOLUTION: There is provided a preparation method, wherein a solution comprising a) a soluble metal salt, b) a nitrogen-containing base selected from the group consisting of methylamine, monoethanolamine, ammonium hydroxide, and mixtures thereof, and c) water is mixed with a polymer containing a metal ion ligand selected from the group consisting of vinylimidazole and vinylpyridine as polymerized units to form a mixture without precipitation, and wherein the metal is silver.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for preparing an antimicrobial composition.

[0002] The constant threat of microbial contamination and its associated impact on health and wellness, as well as the deleterious effects that microorganisms can cause on product aesthetics and durability, have made antimicrobial solutions a widespread component of consumer and institutional products. Many materials, such as textiles, paints, and coatings, as well as building materials, can support microbial growth and are often protected with antimicrobial agents. Some antimicrobial agents, such as triclosan, are no longer acceptable for many of these applications due to human and environmental safety concerns. While some antimicrobial agents are acceptable, they are difficult to apply in or onto materials. Inorganic metal ions, such as silver, copper, and zinc, can provide antimicrobial benefits to materials. However, many metal ion antimicrobial agents are supplied as inorganic microparticles that are difficult to incorporate. While liquid, non-particulate formulations of metal antimicrobial agents are easy to incorporate, these formulations often have poor stability and a short shelf life. Therefore, there is a need for the development of new, stable, liquid, non-particulate formulations of metal ions that are easy to incorporate into and apply to materials and can provide sustained antimicrobial efficacy.

[0003] US 7,390,774 discloses one such formulation. The cited document describes an antimicrobial composition comprising a metal complexed with a polymer, the metal being selected from copper, silver, gold, tin, zinc, and combinations thereof. While such compositions are effective, it has been found that the formulation itself does not have acceptable stability over time. Therefore, there is a need in the art to improve the stability of these metal / polymer antimicrobial compositions.

[0004] The present invention provides a method for preparing a stable formulation, comprising the steps of: i) a) salts of metals, b) nitrogenous bases, and c) water, providing a solution of ii) mixing the solution with a polymer, wherein the polymer contains a metal ion ligand, and solving the problems in the art by providing a method comprising:

[0005] As used herein, "stable" means producing a mixture without precipitation upon mixing. When a solution is said to be unstable, it means that a precipitate is formed upon mixing.

[0006] To achieve a stable formulation of the present invention, the order of addition of the components of the formulation is very important. According to the present method, a solution containing a soluble metal salt, a nitrogen-containing base, and water is provided. Suitable soluble salts of metals are salts of copper, silver, gold, tin, zinc, and combinations thereof. As used herein, soluble means that the metal salt completely dissolves in a solution of water and a nitrogen-containing base. Alternatively, the soluble metal salt may be a salt of copper, silver, zinc, and combinations thereof. Further alternatively, the soluble metal salt is a salt of silver.

[0007] As used herein, "nitrogen-containing base" is defined as a primary amine or ammonium hydroxide. The primary amine can be any primary amine known to those skilled in the art. Examples of suitable primary amines include methylamine, monoethanolamine, and mixtures thereof. In the present invention, a mixture of ammonium hydroxide and a primary amine can also be used. The combination of the metal salt and the primary amine can be achieved by conventional methods known to those skilled in the art.

[0008] Then, this solution is mixed with a polymer containing a metal ion ligand. Suitable polymers containing metal ion ligands are described in US7,390,774 and US7,927,379. The combination of the solution and the polymer can be achieved by conventional methods known to those skilled in the art. Suitable metal ion ligands include vinylimidazole and vinylpyridine.

[0009] According to the present invention, additional water may be added. This water may be added at any time during the process. For example, additional water may be added to the polymer. Alternatively, water may be added after the polymer is mixed with the solution. The amount of water added is determined by the desired metal ion concentration in the final formulation and the desired ratio of metal ions to polymer.

[0010] Additionally, the methods of the present invention can optionally include the addition of one or more antimicrobial agents, provided that the physical and chemical stability of the resulting antimicrobial composition is not substantially affected by such inclusion. Antimicrobial agents suitable for use in the present invention include, for example, 3-iodo-2-propynyl butylcarbamate, 3-isothiazolones, including 2-n-octyl-3-isothiazolone, zinc pyrithione, quaternary ammonium biocides such as dialkyldimethylammonium salts, trazole fungicides such as tebuconazole, and phenols such as 2-thiocyanomethylthiobenzothiazole, thiobendazole, diiodomethyltolylsulfone, and 2,4,4'-trichloro-2'-hydroxydiphenyl ether.

[0011] Some embodiments of the present invention are further illustrated in the following examples, in which all parts and percentages are by weight unless otherwise specified.

[0012] Polymer Description Table I lists the monomer composition of each polymer product.

[0013] [Table I]

[0014] The polymers of the present invention were prepared according to the methods described in US Pat. No. 7,390,774 and US Pat. No. 7,927,379.

[0015] Examples 1 to 9: Methods for formulating antibacterial compositions Metal-containing antimicrobial formulations were prepared using the following three addition order methods with the respective amounts listed in Table II: Method A) Polymer 1, metal nitrate aqueous solution, ammonium hydroxide, deionized water, Method B) Polymer 1, ammonium hydroxide, metal nitrate aqueous solution, deionized water, Method C) Aqueous metal nitrate solution, ammonium hydroxide, polymer 1, deionized water.

[0016] The formulation methods were evaluated by observing precipitation upon mixing after the last ingredient was added. Formulation stability is shown in Table III. Stability is indicated as o and instability or precipitation is indicated as x. Method C results in a stable formulation, the composition having a VI:metal molar ratio of 11.6:1.

[0017] [Table II]

[0018] [Table III]

[0019] Examples 10 to 18: Methods for formulating antibacterial compositions Metal-containing antimicrobial formulations were prepared using the following three addition order methods with the respective amounts listed in Table IV: Method A) Polymer 1, metal nitrate aqueous solution, ammonium hydroxide, deionized water, Method B) Polymer 1, ammonium hydroxide, metal nitrate aqueous solution, deionized water, Method C) Aqueous metal nitrate solution, ammonium hydroxide, polymer 1, deionized water.

[0020] The formulation methods were evaluated by observing precipitation upon mixing after the last ingredient was added. The stability of the formulations is shown in Table V. Stability is indicated as o and instability or precipitation is indicated as x. Method C results in a stable formulation, the composition having a VI:metal molar ratio of 8:1.

[0021] [Table IV]

[0022] [Table V]

[0023] Examples 19-24: Methods of formulating antimicrobial compositions with various polymers Zinc-containing antimicrobial formulations were prepared using the following three addition order methods with the respective amounts listed in Table VI: Method A) A mixture of the polymer shown in Table I, aqueous zinc nitrate, ammonium hydroxide, and deionized water. Method B) A polymer shown in Table 1, ammonium hydroxide, zinc nitrate aqueous solution, deionized water, Method C) Aqueous zinc nitrate solution, ammonium hydroxide, polymer as shown in Table 1, deionized water.

[0024] The formulation process was evaluated by observing precipitation upon mixing after the last ingredient was added. Formulation stability is shown in Table VII. Stability is indicated as o and instability or precipitation is indicated as x. Method C results in a stable formulation.

[0025] Table VI

[0026] [Table VII]

[0027] Examples 25-28: Methods for formulating ammonia-free antimicrobial compositions Zinc-containing antimicrobial formulations were prepared using the following three addition order methods with the respective amounts listed in Table VIII: Method A) Polymer 1, aqueous zinc nitrate solution, a primary amine from Table VIII, deionized water, Method B) Polymer 1, a primary amine from Table VIII, an aqueous zinc nitrate solution, deionized water, Method C) Aqueous zinc nitrate solution, a primary amine from Table VIII, Polymer 1, deionized water.

[0028] The amine:metal molar ratio was maintained at 16:1. Formulation methods were evaluated by observing precipitation upon mixing after the last component was added. Formulation stability is shown in Table IX. Stability is indicated as o and instability or precipitation is indicated as x. Method C results in stable formulations for primary amines.

[0029] [Table VIII]

[0030] [Table IX]

[0031] Examples 29-32: Methods for formulating low metal level antimicrobial compositions Silver-containing antimicrobial formulations were prepared using the following three addition order methods with the respective amounts listed in Table X: Method A) Polymer 1, aqueous silver nitrate solution, ammonium hydroxide, deionized water, Method B) Polymer 1, ammonium hydroxide, silver nitrate aqueous solution, deionized water, Method C) Aqueous silver nitrate solution, ammonium hydroxide, polymer 1, deionized water.

[0032] Formulation methods were evaluated by observing precipitation upon mixing after the last ingredient was added. Formulation stability is shown in Table XI. Stability is indicated as o and instability or precipitation is indicated as x. Method C results in stable 0.05% and 0.1% silver formulations.

[0033] [Table X]

[0034] [Table XI]

[0035] Comparative Example 33: Method of formulating high metal level antibacterial compositions Silver-containing antimicrobial formulations were prepared using the following three addition order methods with the respective amounts listed in Table XII: Method A) Polymer 1, aqueous silver nitrate solution, ammonium hydroxide, deionized water, Method B) Polymer 1, ammonium hydroxide, silver nitrate aqueous solution, deionized water, Method C) Aqueous silver nitrate solution, ammonium hydroxide, polymer 1, deionized water.

[0036] Formulation methods were evaluated by observing precipitation upon mixing after the last ingredient was added. Formulation stability is shown in Table XIII. Stability is indicated as o and instability or precipitation is indicated as x. Method C results in a stable 3% silver formulation.

[0037] Table XII

[0038] [Table XIII]

[0039] Comparative Example 34: Method for formulating an antibacterial composition Silver-containing antimicrobial formulations were prepared using the following three addition order methods with the respective amounts listed in Table XIV: Method A) Polymer 1, aqueous silver nitrate solution, ammonium hydroxide, deionized water, Method B) Polymer 1, ammonium hydroxide, silver nitrate aqueous solution, deionized water, Method C) Aqueous silver nitrate solution, ammonium hydroxide, polymer 1, deionized water.

[0040] Formulation methods were evaluated by observing precipitation upon mixing after the last ingredient was added. Formulation stability is shown in Table XV. Stability is indicated as o and instability or precipitation is indicated as x. Method C results in a stable silver-based formulation with a VI:silver molar ratio of 4.9:1 and an ammonia:metal molar ratio of 6.8:1.

[0041] [Table XIV]

[0042] [Table XV]

[0043] Comparative Example 35: Method for formulating an antibacterial composition Silver-containing antimicrobial formulations were prepared with and without stirring in the amounts listed in Table XVI using the following three addition order methods: Method A) Polymer 1 diluted to 21% solids, aqueous silver nitrate, ammonium hydroxide, deionized water, Method B) Polymer 1 diluted to 21% solids, ammonium hydroxide, silver nitrate aqueous solution, deionized water, Method C) Aqueous silver nitrate solution, ammonium hydroxide, polymer 1 diluted to 21% solids, deionized water.

[0044] The formulation methods were evaluated by observing precipitation upon mixing after the last ingredient was added. The stability of the formulations is shown in Table XVII. Stability is indicated as o and instability or precipitation is indicated as x. Method C results in a stable formulation.

[0045] [Table XVI]

[0046] [Table XVII]

Claims

1. 1. A method for preparing a stable formulation, comprising: i) a) soluble salts of metals; b) a nitrogen-containing base selected from the group consisting of methylamine, monoethanolamine, ammonium hydroxide, and mixtures thereof; and c) water; providing a solution of ii) mixing the solution with a polymer containing, as polymerized units, metal ion ligands selected from the group consisting of vinylimidazole and vinylpyridine; The term "stable" means that when mixed together, they form a mixture without precipitating, The method wherein the metal is silver.

2. 10. The method of claim 1, wherein the nitrogen-containing base is ammonium hydroxide.

3. 10. The method of claim 1, wherein the nitrogen-containing base is methylamine, monoethanolamine, or a mixture thereof.

4. The method of claim 1 wherein water is added to the polymer.

5. The method of claim 1 , wherein water is added after the polymer is mixed with the solution.

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