ANTIMICROBIAL COMPOSITIONS COMPRISING FOOD APPROVED ANTIMICROBIALS AND ZINC PYRITHIONE

Abstract

The present invention relates to combinations of zinc pyrithione and food-approved antimicrobials which provide a synergistic antimicrobial effect. The food approved antimicrobials are selected from sodium sulfite, sodium bisulfite, potassium metabisulfite, potassium sulfite, calcium sulfite, calcium hydrogen sulfite, potassium hydrogen sulfite, sodium nitrate, potassium nitrate, and lysozyme. These combinations are useful for the protection of any living or non-living material, such as food, crops, plants, fruits, wood, wood products, leather, natural or synthetic textile, fibers, non-wovens, technical textile, plasticized materials and non-plasticized thermoplastics as polypropylene, polyvinylchloride, etc. . . . , paper, wall paper, insulation material, laminates, amino moulding compounds, paints and coatings, fabrics, floor coverings, synthetic fibres like plasticized polymers, hessian, rope and cordage and other biodegradable materials against deterioration due to the action of microorganisms such as bacteria, fungi, yeasts, algae, and the like. Also, the present invention relates to compositions comprising a combination of zinc pyrithione and said food-approved antimicrobials; in respective proportions to provide a synergistic antimicrobial effect.

Claims

1. A composition comprising a combination of zinc pyrithione as a component (I) and as a component (II) a food-approved antimicrobial from selected sodium sulfite, sodium bisulfite, potassium metabisulfite, potassium sulfite, calcium sulfite, calcium hydrogen sulfite, potassium hydrogen sulfite, sodium nitrate, potassium nitrate, and lysozyme; wherein the ratio by weight of component (I) to component (II) ranges from 4:1 to 1:4 to provide a synergistic antimicrobial effect.

2. The composition as claimed in claim 1 wherein component (II) is selected from sodium sulfite, sodium bisulfite, potassium metabisulfite, potassium sulfite, calcium sulfite, calcium hydrogen sulfite, potassium hydrogen sulfite, sodium nitrate and potassium nitrate.

3. The composition as claimed in claim 1 wherein component (II) is selected from sodium sulfite, sodium bisulfite, potassium metabisulfite, potassium sulfite, calcium sulfite, calcium hydrogen sulfite, and potassium hydrogen sulfite.

4. The composition as claimed in claim 1 wherein component (II) is selected from sodium nitrate and potassium nitrate.

5. The composition as claimed in claim 1 wherein component (II) is lysozyme.

6. The composition as claimed in claim 1 wherein component (II) is selected from sodium sulfite, sodium bisuflite, and lysozyme.

7. The composition as claimed in claim 1 wherein component (II) is selected from sodium sulfite and lysozyme.

8. The composition as claimed in of claim 1 wherein the ratio by weight of component (I) to component (II) ranges from 3:1 to 1:3, or 2:1 to 1:2.

9. (canceled)

10. The use according to claim 9 wherein the ratio by weight of component (I) to component (II) ranges from 3:1 to 1:3, or 2:1 to 1:2.

11. A food packaging material coated with a composition as claimed in claim 1.

12. A method of controlling microbial growth on leather, natural or synthetic textile, fibers, non-wovens, technical textile, plasticized materials, non-plasticized thermoplastics, paper, wall paper, insulation material, laminates, amino moulding compounds, paints, coatings, fabrics, floor coverings, synthetic fibres, hessian, rope and cordage, which comprises applying to said materials an antimicrobially effective amount of a combination of zinc pyrithione as a component (I) and as a component (II) a food-approved antimicrobial selected from sodium sulfite, sodium bisulfite, potassium metabisulfite, potassium sulfite, calcium sulfite, calcium hydrogen sulfite, potassium hydrogen sulfite, sodium nitrate, potassium nitrate, and lysozyme; wherein the ratio by weight of component (I) to component (II) ranges from 4:1 to 1:4 to provide a synergistic antimicrobial effect.

13. A method of controlling microbial growth on wood or wood products, which comprises applying to said wood or wood products an antimicrobially effective amount of a combination of zinc pyrithione as a component (I) and as a component (II) a food-approved antimicrobial selected from sodium sulfite, sodium bisulfite, potassium metabisulfite, potassium sulfite, calcium sulfite, calcium hydrogen sulfite, potassium hydrogen sulfite, sodium nitrate, potassium nitrate, and lysozyme; wherein the ratio by weight of component (I) to component (II) ranges from 4:1 to 1:4 to provide a synergistic antimicrobial effect.

14. A method of controlling microbial growth on engineering materials, which comprises applying to said engineering materials an antimicrobially effective amount of a combination of zinc pyrithione as a component (I) and as a component (II) a food-approved antimicrobial selected from sodium sulfite, sodium bisulfite, potassium metabisulfite, potassium sulfite, calcium sulfite, calcium hydrogen sulfite, potassium hydrogen sulfite, sodium nitrate, potassium nitrate, and lysozyme; wherein the ratio by weight of component (I) to component (II) ranges from 4:1 to 1:4 to provide a synergistic antimicrobial effect.

15. A method of controlling microbial growth on plants, parts of plants, fruit and seeds, which comprises applying to said plants, parts of plants, fruit and seeds an antimicrobially effective amount of a combination of zinc pyrithione as a component (I) and as a component (II) a food-approved antimicrobial selected from sodium sulfite, sodium bisulfite, potassium metabisulfite, potassium sulfite, calcium sulfite, calcium hydrogen sulfite, potassium hydrogen sulfite, sodium nitrate, potassium nitrate, and lysozyme; wherein the ratio by weight of component (I) to component (II) ranges from 4:1 to 1:4 to provide a synergistic antimicrobial effect.

16. A method of controlling the growth of microorganisms on food that is packaged with food packaging materials which method comprises coating or incorporating in said food packaging materials a combination of zinc pyrithione as a component (I) and as a component (II) a food-approved antimicrobial selected from sodium sulfite, sodium bisulfate, potassium metabisulfite, potassium sulfite, calcium sulfite, calcium hydrogen sulfite, potassium hydrogen sulfite, sodium nitrate, potassium nitrate, and lysozyme, wherein the ratio by weight of component (I) to component (II) ranges from 4:1 to 1:4 to provide a synergistic antimicrobial effect.

Description

EXPERIMENTAL PART

Experiment 1: Poison Plate Assay

[0060]

TABLE-US-00001 Name of component (I): zinc pyrithione Name of component (II): sodium sulfite (II-a) lysozyme (II-b) Stock solutions: 8000 ppm in sterile deionised water. Test combinations: % product A + % product B 100 + 0 80 + 20 67 + 33 50 + 50 33 + 67 20 + 80 0 + 100

[0061] In the test combinations above, product A is component (I), i.e. zinc pyrithione, and product B is a component (II), i.e. either sodium sulfite (II-a) or lysozyme (II-b).

[0062] Concentration series of total actives: a series of 24 concentrations increasing with steps of :0.27-0.35-0.47-0.63-0.84-1.13-1.50-2.00-2.67-3.56-4.75-6.33-8.44-11.25-15.00-20.00-26.70-35.60-47.46-63.28-84.38-112.50-150.00-200.00 ppm. [0063] Culture medium: bacteria: nutrient broth (3 g beef extract and 5 g peptone in 1 liter deionised water, pH=6.8.) [0064] Experimental set up: 96-well plates containing 300 l pf inoculum plus 0.75 l of a 400 concentrated stock solution of the test compounds per well. [0065] Species of test organisms: Escherichia coli LMG 8063 [0066] Staphylococcus aureus LMG 8195/ATCC 6538P [0067] Inoculum: the nutrient medium is inoculated with an actively growing liquid culture of the test bacteria. [0068] Culture conditions: 28 C., 70% relative humidity, incubation in darkness. [0069] Evaluation: 7 days after inoculation.

[0070] Synergy calculation: MIC values (minimum inhibitory concentration in ppm total active ingredient) were noted and synergy was calculated using the Synergy Index method (Kull, F. C., P. C. Eismann, H. D. Sylvestrowicz, and R. L. Mayer (1961) Mixtures of quaternary ammonium compounds and long-chain fatty acids as antifungal agents Applied Microbiology 9: 538-541; also see Steinberg, D. C. (2000) Measuring synergy cosmetics & Toiletries 115(11): 59-62).

[00001]$\mathrm{Synergy}.Math..Math.\mathrm{Index}\left(S.Math..Math.I\right)=\frac{Q_a}{Q_A}+\frac{Q_b}{Q_B}$

wherein: [0071] Q.sub.A is the concentration of compound A in ppm, acting alone, which produced an end point (e.g. MIC), [0072] Q.sub.a is the concentration of compound A in ppm, in the mixture, which produced an end point (e.g. MIC), [0073] Q.sub.B is the concentration of compound B in ppm, acting alone, which produced an end point (e.g. MIC), [0074] Q.sub.b is the concentration of compound B in ppm, in the mixture, which produced an end point (e.g. MIC).

[0075] When the Synergy Index is greater than 1.0, antagonism is indicated. When the SI is equal to 1.0, additivity is indicated. When the SI is less than 1.0, synergism is demonstrated.

TABLE-US-00002 TABLE 1 MIC-values (minimum inhibitory concentration in ppm) and synergy index of combinations of zinc pyrithione (component (I)) with sodium sulfite (II-a) tested against Escherichia coli MIC-values Synergy % (I) + % (II-a) in ppm Index Escherichia coli 100 + 0 3.60 80 + 20 3.60 0.80 67 + 33 3.60 0.67 50 + 50 4.80 0.68 33 + 67 8.40 0.80 20 + 80 8.40 0.49 0 + 100 267

TABLE-US-00003 TABLE 2 MIC-values (minimum inhibitory concentration in ppm) and synergy index of combinations of zinc pyrithione (component (I)) with lysozyme (II-b) tested against Staphylococcus aureus MIC-values Synergy % (I) + % (II-b) in ppm Index Staphylococcus aureus 100 + 0 2.00 80 + 20 2.00 0.80 67 + 33 2.70 0.90 50 + 50 2.70 0.68 33 + 67 3.60 0.61 20 + 80 4.80 0.49 0 + 100 267

Experiment 2: Poison Plate Assay

[0076]

TABLE-US-00004 Name of component (I): zinc pyrithione Name of component (II): sodium bisulfite (II-c) Stock solutions: 8000 ppm in sterile deionised water. Test combinations: % product A + % product B 100 + 0 80 + 20 67 + 33 50 + 50 33 + 67 20 + 80 0 + 100

[0077] In the test combinations above, product A is component (I), i.e. zinc pyrithione, and product B is a component (II), i.e. either sodium bisulfite (II-c).

[0078] Concentration series of total actives: a series of 24 concentrations increasing with steps of :0.27-0.35-0.47-0.63-0.84-1.13-1.50-2.00-2.67-3.56-4.75-6.33-8.44-11.25-15.00-20.00-26.70-35.60-47.46-63.28-84.38-112.50-150.00-200.00 ppm. [0079] Culture medium: half strength potato dextrose broth (2 g potato infusion and 10 g bacto dextrose in I litre deionised water) [0080] Experimental set up: 96-well plates containing 300 l pf inoculum plus 0.75 l of a 400 concentrated stock solution of the test compounds per well. [0081] Species of test organisms: Saccharomyces cerevisiae CBS 8803 [0082] Inoculum: the nutrient medium is inoculated with an actively growing liquid culture of the test bacteria. [0083] Culture conditions: 28 C., 70% relative humidity, incubation in darkness. [0084] Evaluation: 7 days after inoculation. [0085] Synergy calculation: as procedure of Experiment 1

TABLE-US-00005 TABLE 3 MIC-values (minimum inhibitory concentration in ppm) and synergy index of combinations of zinc pyrithione (I) with sodium bisulfite (II-c) tested against Saccharomyces cerevisiae MIC-values Synergy % (I) + % (II-c) in ppm Index Saccharomyces cerevisiae 100 + 0 2.00 80 + 20 2.00 0.80 67 + 33 2.67 0.90 50 + 50 3.56 0.91 33 + 67 4.75 0.81 20 + 80 8.45 0.87 0 + 100 267