HYDROPHOBIC ANTIMICROBIAL AGENTS

Abstract

The present invention relates to a hydrophobic antimicrobial agent comprising a mineral material, which is surface coated with a copper and/or silver salt of at least one fatty acid, a method for its manufacture, wherein at least one fatty acid and at least one copper and/or silver salt are dissolved in a non-aqueous solvent, the solutions are combined, the copper and/or silver salt of the at east one fatty acid is precipitated by adding water, separated, and surface coated onto the mineral material. Furthermore, the present invention relates to the hydrophobic antimicrobial agent obtained by said method, the use thereof as a filler, products comprising the hydrophobic antimicrobial agent, and the use of a copper and/or silver salt of at least one fatty acid for surface coating a mineral material.

Claims

1.-19. (canceled)

20. A hydrophobic antimicrobial agent comprising a mineral material surface coated with a copper salt and/or silver salt of at least one fatty acid.

21. The hydrophobic antimicrobial agent according to claim 20, wherein the mineral material is selected from the group consisting of natural ground calcium carbonate (GCC), precipitated calcium carbonate (PCC), and mixtures thereof.

22. The hydrophobic antimicrobial agent according to claim 20, wherein the natural ground calcium carbonate (GCC) is selected from the group consisting of marble, chalk, limestone, and mixtures thereof.

23. The hydrophobic antimicrobial agent according to claim 20, wherein the precipitated calcium carbonate (PCC) is selected from the group consisting of precipitated calcium carbonates having aragonitic, vateritic or calcitic crystal forms, and mixtures thereof.

24. The hydrophobic antimicrobial agent according to claim 20, wherein the mineral material has a) a weight median particle size d.sub.50 in the range from 0.1 μm to 20 μm, and/or b) a top cut particle size (d.sub.98) of not more than 100 μm, and/or c) a specific surface area (BET) of from 0.5 to 50 m.sup.2/g as measured by the BET nitrogen method.

25. The hydrophobic antimicrobial agent according to claim 20, wherein the mineral material has a) a weight median particle size d.sub.50 in the range from 1.5 μm to 3.5 μm, and/or b) a top cut particle size (d.sub.98) of from 5.8 to 7.4 μm, and/or c) a specific surface area (BET) of from 5 to 10 m.sup.2/g as measured by the BET nitrogen method.

26. The hydrophobic antimicrobial agent according to to claim 20, wherein the at least one fatty acid is selected from the group consisting of aliphatic carboxylic acids having from 5 to 24 carbon atoms and mixtures thereof.

27. The hydrophobic antimicrobial agent according to to claim 20, wherein the at least one fatty acid is selected from the group consisting of pentanoic acid, hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, lauric acid, tridecanoic acid, myristic acid, pentadecanoic acid, palmitic acid, heptadecanoic acid, stearic acid, nonadecanoic acid, arachidic acid, heneicosylic acid, behenic acid, tricosylic acid, lignoceric acid, and mixtures thereof.

28. The hydrophobic antimicrobial agent according to claim 20, wherein the hydrophobic antimicrobial agent contains 0.1 to 10 wt % of a copper and/or silver salt of at least one fatty acid, based on the total weight of the mineral material.

29. The hydrophobic antimicrobial agent according to claim 20, wherein the hydrophobic antimicrobial agent contains 3 to 4 wt % of a copper and/or silver salt of at least one fatty acid, based on the total weight of the mineral material.

30. The hydrophobic antimicrobial agent according to claim 20, wherein the hydrophobic antimicrobial agent has a moisture pickup susceptibility of from 0.05 to 1 mg of H.sub.2O/g of solid.

31. The hydrophobic antimicrobial agent according to claim 20, wherein the hydrophobic antimicrobial agent has a moisture pickup susceptibility of from 0.2 to 0.3 mg of H.sub.2O/g of solid.

32. A method for the manufacture of the hydrophobic antimicrobial agent of claim 20, characterized by the steps of a) providing at least one fatty acid, b) providing at least one copper and/or silver salt, c) providing a mineral material, d) dissolving the at least one fatty acid of step a) in a first non-aqueous solvent, e) dissolving the at least one copper and/or silver salt of step b) in a second non-aqueous solvent, f) combining the solutions of step d) and e), g) precipitating the copper and/or silver salt of the at least one fatty acid by adding water to the combined solutions of step f), h) separating the precipitated copper and/or silver salt of at least one fatty acid from the reaction mixture of step g), and i) surface coating the mineral material of step c) with the precipitated copper and/or silver salt of at least one fatty acid of step h).

33. The method according to claim 32, wherein the copper and/or silver salt of step b) is selected from the group consisting of copper acetate, copper pyrophosphate, copper nitrate, copper chloride, copper oxalate, silver chloride, silver acetate, silver nitrate, and silver sulfate, their hydrates, and mixtures thereof.

34. The method according to claim 32, wherein the at least one copper and/or silver salt of step b) is provided in an amount of from 0.5 to 75 wt % based on the total weight of the at least one fatty acid of step a).

35. The method according to claim 32, wherein the first non-aqueous solvent is selected from the group consisting of ethanol, methanol, acetone, acetonitrile, dioxane, ethyl acetate, toluene, xylene, tetrahydrofuran, and mixtures thereof.

36. The method according to claim 32, wherein the second non-aqueous solvent is selected from the group consisting of ethanol, methanol, acetone, acetonitrile, dioxane, ethyl acetate, toluene, xylene, tetrahydrofuran, and mixtures thereof.

37. The method according to claim 32, wherein dissolution steps d) and/or e), independently from each other, are carried out at a temperature of from 25 to 80° C.

38. The method according to claim 32, wherein combination step f) is carried out under stirring.

39. The method according to claim 32, wherein combination step f) is carried out under stirring at the temperature of any one of steps d) or e).

40. The method according to claim 32, wherein in coating step i), the mineral material of step c) is combined with the copper and/or silver salt of at least one fatty acid of step h) under stirring.

41. The method according to claim 32, wherein in coating step i), the mineral material of step c) is combined with the copper and/or silver salt of at least one fatty acid of step h) under stirring at a temperature of from 80 to 110° C.

42. The method according to claim 32, wherein in coating step i), the copper and/or silver salt of at least one fatty acid of step h) is combined with the mineral material of step c) in an amount of from 0.1 to 10 wt % based on the total weight of the mineral material.

43. A hydrophobic antimicrobial agent obtained by the method according to to claim 32.

44. A product comprising the hydrophobic antimicrobial agent of claim 20.

45. The product of claim 44, wherein the product is selected from the group consisting of polymers, paints, adhesives, coatings, rubber, sealants, and cosmetics.

46. A product comprising the hydrophobic antimicrobial agent of claim 43.

47. The product of claim 46, wherein the product is selected from the group consisting of polymers, paints, adhesives, coatings, rubber, sealants, and cosmetics.

Description

EXAMPLES

1. Analytical Methods

[0114] Particle Size Distribution (Mass % Particles with a Diameter<X) and Weight Median Diameter (d.sub.50) of a Particulate Material

[0115] Particle sizes were determined by using a Sedigraph™ 5120 instrument of Micromeritics Instrument Corporation. The method and the instrument are known to the skilled person and are commonly used to determine the particle size of fillers and pigments. The measurements were carried out in an aqueous solution of 0.1 wt % Na.sub.4P.sub.2O.sub.7. The samples are dispersed using a high speed stirrer and supersonics.

BET Specific Surface Area of a Material

[0116] The “specific surface area” (expressed in m.sup.2/g) of a material as used throughout the present document is determined by the Brunauer Emmett Teller (BET) method with nitrogen as adsorbing gas and by use of a ASAP 2460 instrument from Micromeritics. The method is well known to the skilled person and defined in ISO 9277:2010. Samples are conditioned at 100° C. under vacuum for a period of 60 min prior to measurement. The total surface area (in m.sup.2) of said material can be obtained by multiplication of the specific surface area (in m.sup.2/g) and the mass (in g) of the material.

Moisture Pick Up Susceptibility

[0117] The moisture pick up susceptibility of a material as referred to herein is determined in mg moisture/g after exposure to an atmosphere of 10% and 85% relative humidity, respectively, for 2 hours at a temperature of +23° C. (±2° C.). For this purpose, the sample is first kept at an atmosphere of 10% relative humidity for 2 hours, then the atmosphere is changed to 85% relative humidity at which the sample is kept for another 2 hours. Finally, the atmosphere is changed to 10% of humidity for 30 minutes. The weight increase between 10% and 85% relative humidity is then used to calculate the moisture pick-up in mg moisture/g of sample.

X-Ray Diffraction (XRD)

[0118] XRD experiments are performed on the samples using rotatable PMMA holder rings. Samples are analysed with a Bruker D8 Advance powder diffractometer obeying Bragg's law. This diffractometer comprises a 2.2 kW X-ray tube, a sample holder, a θ-θ-goniometer, and a VANTEC-1 detector. Nickel-filtered Cu-Kα radiation is employed in all experiments. The profiles are chart recorded automatically using a scan speed of 0.7° per min in 2 θ (XRD GV_7600). The resulting powder diffraction patterns are classified by mineral content using the DIFFRACsuite software packages EVA and SEARCH, based on reference patterns of the ICDD PDF-2 database (XRD LTM_7603).

[0119] Quantitative analysis of diffraction data refers to the determination of amounts of different phases in a multi-phase sample and has been performed using the DIFFRACsuite software package TOPAS (XRD LTM_7604). In detail, quantitative analysis allows to determine structural characteristics and phase proportions with quantifiable numerical precision from the experimental data itself. This involves modelling the full diffraction pattern using the Rietveld approach such that the calculated pattern(s) duplicates the experimental one.

Inductively Coupled Plasma (ICP) Analysis

[0120] Prior to the analysis, 0.2 g of the samples (i.e. the copper and/or silver salt of at least one fatty acid) were digested in a mixture containing 5 ml of 69% HNO.sub.3, 2 ml 30% H.sub.2O.sub.2 and 3 ml H.sub.2O. The samples were decomposed by microwave assisted digestion at elevated temperature and pressure, which is generated by the vapor pressure of the heated liquids contained in the chamber, using the following microwave temperature program: from 20° C. to 85° C. for 7 min, then from 85° C. to 160° C. for 7 min and, finally, from 160° C. to 180° C. for 12 min.

[0121] After the decomposition, the solutions were filled up to 50 ml with distilled water and analyzed by ICP-OES Optima 8300 from Perkin Elmer.

2. Material

Mineral Material

[0122] Ground natural calcium carbonate (d.sub.50=1.8 μm, d.sub.98=5.7 μm; BET=3.4 m.sup.2/g; moisture pickup susceptibility=1.3 mg/g solid)

Fatty Acid

[0123] Stearic acid, reagent grade 95% (from Sigma Aldrich; CAS No. 57-11-4)

Copper/Silver Salt

[0124] Copper acetate monohydrate (from Sigma Aldrich; CAS No. 6046-93-1) Silver nitrate (from Sigma Aldrich; CAS No. 7761-88-8)

Non Aqueous Solvent

[0125] Ethanol (from Sigma Aldrich; CAS No. 64-17-5)

Other Solvent

[0126] Distilled water

Polymer

[0127] Polyethylene LLDPE Dowlex2631.10UE supplied by Resinex

3. Preparation

3.1. Preparation of Copper/Silver Salt of a Fatty Acid

3.1.1. Copper Stearate

[0128] Copper stearate was prepared by first dissolving stearic acid in ethanol in a 1 l round bottom flask in the amounts given in table 1 at 50° C. until a complete dissolution of the latter was achieved. At the same time, in a different bottom flask, copper acetate monohydrate was dissolved in ethanol in the amounts given in table 1, at the same temperature. Once both components were completely dissolved, the copper acetate monohydrate solution was added to the stearic acid solution dropwise and mixed for 2 hours at 50° C. Finally, water in the amount given in table 1 was added to the mixture, precipitating the final product. The product was separated by filtration under vacuum using Whatman filters grade 589, washed with water and dried in an oven at 50° C. overnight. The product was deagglomerated manually.

TABLE-US-00001 TABLE 1 Stearic Copper acetate Water for the acid Ethanol monohydrate Ethanol precipitation Sample (g) (ml) (g) (ml) (ml) 1 100 300 63.5 400 350 2 15.88 200 250 3 3.97 100 200 4 0.99 50 175

[0129] The obtained copper stearate treatment agents were analyzed using XRD and ICP techniques (cf. table 2).

TABLE-US-00002 TABLE 2 ICP XRD data (%) analysis (%) Stearic Copper Amorphous Amount Sample acid stearate content Σ of Cu 1 14 37 49 100 13.6 2 26 34 40 100 5.0 3 45 17 37 99 1.3 4 54 6 40 100 0.3 Stearic acid 80 0 15 95 0 reagent grade, 95%

3.1.2. Silver Stearate

[0130] Silver stearate was prepared by first dissolving stearic acid in ethanol in a 5 l bottom flask in the amounts given in table 3 at 50° C. until a complete dissolution of the latter was achieved. At the same time, in a different bottom flask, silver nitrate was dissolved in ethanol in the amounts given in table 3, at the same temperature. Once both components were completely dissolved, the silver nitrate solution was added to the stearic acid solution and mixed for 2 hours at 50° C. Finally, water in the amount given in table 3 was added to the mixture, precipitating the final product. The product was separated by filtration under vacuum using Whatman filters grade 589, washed with water and dried in an oven at 50° C. overnight. The product was deagglomerated manually.

TABLE-US-00003 TABLE 3 Stearic Silver Water for the acid Ethanol nitrate Ethanol precipitation Sample (g) (ml) (g) (ml) (ml) 5 100 300 59.5 2000 1150 6 14.88 1000 650 7 3.72 500 400 8 0.93 250 275

[0131] The obtained silver stearate treatment agents were analysed using XRD and ICP techniques (cf. table 4).

TABLE-US-00004 TABLE 4 ICP XRD data (%) analysis (%) Stearic Silver Amorphous Amount Sample acid stearate content Σ of Ag 5 15 48 37 100 19.3 6 40 30 30 100 4.7 7 56 16 28 100 1.5 8 68 5 27 100 0.3 Stearic acid 80 0 15 95 0 reagent grade, 95%
3.2. Surface Coating of Calcium Carbonate with Copper/Silver Salt of a Fatty Acid

[0132] Each one of samples 1 to 8 as well as, as a comparative sample, stearic acid, were coated onto calcium carbonate, as follows:

[0133] Calcium carbonate was dried for 16 hours at 160° C. The coater (a Lödige ploughshare® mixer of 5 litres) as heated to 110° C. for 1 hour. Then, 1163 g of the dried calcium carbonate was put inside the coater and stirred for 5 minutes at 100 rpm. Subsequently, the respective sample was added in an amount based on the weight of the calcium carbonate as mentioned in table 5 below, and both components, calcium carbonate and the respective sample, were mixed for further 30 min. at 1000 rpm. The mixer was cooled down to 60° C. and maintained at 100 rpm for 1 hour. Finally, the coated calcium carbonate is removed.

4. Characterization

4.1. Moisture Pickup Susceptibility

[0134] Subsequently, hydrophobicity of the coated calcium carbonate was evaluated by determination of the respective moisture pickup susceptibility.

TABLE-US-00005 TABLE 5 Moisture pickup susceptibility Sample No. wt % (mg of H.sub.2O/g of solid) Stearic acid 0.5 wt % 0.75 Stearic acid 1 wt % 0.21 Stearic acid 2 wt % 0.28 1 1 wt % 0.75 1 2 wt % 0.47 1 5 wt % 0.55 2 1 wt % 0.52 2 2 wt % 0.19 3 1 wt % 0.27 3 2 wt % 0.16 4 1 wt % 0.18 4 2 wt % 0.16 4 5 wt % 0.25 4 10 wt % 0.25 4 0.05 wt % 1.39 (comparative) 4 12 wt % 0.22* (comparative) Stearic acid 0.5 wt % 0.75 Stearic acid 1 wt % 0.21 Stearic acid 2 wt % 0.28 5 1 wt % 0.79 5 2 wt % 0.54 5 3.5 wt % 0.36 6 1 wt % 0.44 6 2 wt % 0.23 7 1 wt % 0.28 7 2 wt % 0.19 8 1 wt % 0.18 8 2 wt % 0.15 *agglomerates were formed; an amount of copper stearate remained in the coater drum

[0135] From table 5, it can be taken that calcium carbonate coated with inventive copper or silver stearates, provides comparable results as regards hydrophobicity at sometimes somewhat higher but acceptable amounts considering that at the same time antimicrobial protection is provided.

[0136] As regards the selection of proper amounts, it can be taken from the comparative examples that at an amount of 0.05 wt % copper stearate, the moisture pickup susceptibility significantly increased, whereas at an amount of 12 wt % no significant decrease of the moisture pickup susceptibility could be observed, but instead an agglomeration of the copper stearate, part of which remained in the coater drum.

[0137] Accordingly, a proper selection of the amount of stearate appears to be crucial for obtaining a hydrophobic antimicrobial agent having an effective antimicrobial activity, a satisfying hydrophobicity, and being still processable.

4.2. Antimicrobial Activity

[0138] In the following tests, antimicrobial activity of silver stearate and copper stearate coated onto calcium carbonate and embedded in a polyethylene formulation was evaluated in view of the bacterial test organism Escherichia coli (DSM 1576/JISZ test 2801).

4.2.1. Sample Preparation

[0139] Embedment of Metal Stearate Coated Calcium Carbonate into Polyethylene Formulation

[0140] The following samples were prepared: [0141] 2 test pieces (4×4 cm.sup.2) of non-treated calcium carbonate embedded in a polyethylene formulation [0142] 5 test pieces (4×4 cm.sup.2) of metal stearate coated calcium carbonate as described above and embedded in a polyethylene formulation

[0143] Pellets were produced on a twin-screw extruder 25:1 from Three Tec (Extruder Type ZE12, die: 0.5 mm) with the following line settings: [0144] Extruder temperatures: 20° C. (feeding)-190° C./210° C./210° C./190° C. [0145] Feeding speed: 7.5-10% [0146] Screw speed: 25-35 rpm [0147] Conveyor speed: 1.5-2.25 rpm [0148] Cut speed: 14-22 rpm

[0149] The polymer used is a linear low-density polyethylene (LLDPE) that can be obtained from Resinex under the tradename Dowlex2631.10UE.

Injection

[0150] Plates were made in a mini injection moulder IM12 from Xplore Instruments B.V. The 8 mL (40×40×5 mm) barrel (square) is filled in with pellets produced as described previously with the following settings: [0151] Barrel temperature: 220° C. [0152] Preheating time: 2 min [0153] Mould temperature: 80° C. [0154] Pressure (Time): 7 bars (2 s), from 7 to 8 bars (3 s), 8 bars (holding pressure, 12 s)

4.2.2. Results

[0155] An antimicrobial surface activity test according to ISO 22196/JIS Z 2801:2000 (Japanese Industrial Standard procedure) and described in LTM_1041 using the test organism Escherichia coli (DSM 1576) was conducted. The following amendments from the test set-up were done: [0156] 1. Two test pieces per metal stearate were available for the experiment. Results were obtained at 24 and 72 hours of incubation. The series of results obtained at 24 and 72 hours, were performed independently. [0157] 2. The size of the test pieces was 4×4 cm.sup.2 (instead of 5×5 cm.sup.2). However, the area finally being in contact with the test organism was according to the norm (4×4 cm.sup.2). [0158] 3. The test pieces were cleaned with 70% ethanol in water (w/w) before usage and air dried. [0159] 4. Test bacteria were not released from the test pieces using a sterile stomacher pouch but instead by adding 10 ml SCDLP broth directly into the petri dish and by gently massaging the test piece with a Drigalski spatula.

TABLE-US-00006 TABLE 6 CaCO.sub.3 filler CaCO.sub.3 filler coated with x coated with x wt % of copper Incubation Antimicrobial wt % of copper Incubation Antimicrobial stearate sample No. time (h) reduction (%) .sup.a stearate sample No. time (h) reduction (%) .sup.b Stearic acid 24 — Stearic acid 72 — (control) (control) 2 9.5 2 21.1 (2 wt %) (2 wt %) 3 8.9 3 15.8 (1 wt %) (1 wt %) 3 14.7 3 9.8 (2 wt %) (2 wt %) 4 9.0 4 14.4 (1 wt %) (1 wt %) 4 17.2 4 42.3 (2 wt %) (2 wt %) .sup.a (Log (cfu/ml) of samples at t = 24 h) * 100/((Log (cfu/mL) of ‘control sample’ at t = 24 h .sup.b (Log (cfu/ml) of samples at t = 72 h) * 100/((Log (cfu/mL) of ‘control sample’ at t = 72 h

TABLE-US-00007 TABLE 7 CaCO.sub.3 filler CaCO.sub.3 filler coated with x coated with x wt % of silver Incubation Antimicrobial wt % of silver Incubation Antimicrobial stearate sample No. time (h) reduction (%) .sup.a stearate sample No. time (h) reduction (%) .sup.b Stearic acid 24 — Stearic acid 72 — (control) (control) 6 29.7 6 25.0 (2 wt %) (2 wt %) 7 13.3 7 8.8 (1 wt %) (1 wt %) 7 26.6 7 32.7 (2 wt %) (2 wt %) 8 14.5 8 9.6 (1 wt %) (1 wt %) 8 8.1 8 3.5 (2 wt %) (2 wt %) .sup.a (Log (cfu/ml) of samples at t = 24 h) * 100/((Log (cfu/mL) of ‘control sample’ at t = 24 h .sup.b (Log (cfu/ml) of samples at t = 72 h) * 100/((Log (cfu/mL) of ‘control sample’ at t = 72 h

[0160] The coating containing metal stearate supported on ground natural calcium carbonate and embedded in a polyethylene formulation showed clear antimicrobial activity against the test organism Escherichia coli. Reduction in bacteria growth was seen in both cases, using silver and copper stearate coated calcium carbonate.