BIOCIDAL POLYURETHANE SYSTEMS, METHODS FOR THEIR PREPARATION AND USES THEREOF

Abstract

The invention relates to the field of polymers, in particular to polymer systems based on polyurethane (PU) having abroad spectrum biocidal activity and the use thereof in the manufacture of biocidal products. Provided is a process to provide a biocidal polyurethane-iodin e (PU-I) complex, comprising (i) dissolving at least one iodine source into one or more raw materials used for preparing the desired polyurethane (PU) to obtain a single phase iodine system, followed by (ii) conducting a PU polymerization reaction in the presence of the single phase iodine system to generate a biocidal PU-I complex in situ.

Claims

1. A process to provide a biocidal polyurethane-iodine (PU-I) complex, comprising (i) dissolving at least one iodine source into one or more raw materials used for preparing a desired polyurethane (PU) to obtain a single phase iodine system, followed by (ii) conducting a PU polymerization reaction in the presence of the single phase iodine system to generate a biocidal PU-I complex in situ.

2. The process according to claim 1, wherein the at least one iodine source is selected from the group consisting of elemental iodine, polyvinylpyrrolidone-iodine (PVP-I), iodide salts, and any combination thereof.

3. The process according to claim 2, wherein the at least one iodine source is elemental iodine, optionally combined with PVP-I.

4. The process according to claim 2 or 3, wherein said PVP—I contains 1-25% available iodine and 2-35% total iodine.

5. The process according to any one of claims 1-4, comprising dissolving at least one iodine source in a polymerization mixture comprising (i) polyol; (ii) isocyanate; and (iii) a chain extender, crosslinker, catalyst, surfactant, solvent and/or additive used in the synthesis of the polyurethane to provide a thermoplastic or thermoset polyurethane-iodine complex.

6. The process according to any one of claims 1-4, comprising dissolving at least one iodine source in a polyol, a polyol blend, a low molecular weight alcohol with functionality 2, a low molecular weight amine with functionality ≥2 and/or solvent, followed by the addition of the desired isocyanate(s) to initiate the polyurethane reaction.

7. The process according to claim 5 or 6, wherein the isocyanate comprises an aliphatic di-, tri- or polyisocyanate, an aromatic di-, tri- or polyisocyanate, or any combination thereof.

8. The process according to any one of claims 5-7, wherein the polyol is selected from the group consisting of polyether polyol, polyester polyol, polycarbonate polyol, polycaprolactone polyol, polyacrylate polyol, and any combination thereof.

9. The process according to claim 5, wherein the chain extender is a low molecular weight diol or diamine, or any combination thereof.

10. The process according to claim 5, wherein the crosslinker is a low molecular weight alcohol or amine with a functionality of 2 or more.

11. The process according to any one of the preceding claims, comprising the use of a polyurethane catalyst, preferably a tertiary amine, metallic compound, or any combination thereof.

12. The process according to any one of the preceding claims, where the polyurethane polymerization reaction is conducted via multi-step, one-step bulk or solvent polymerization to form the final PU-I complex in pre-polymer formation stages or one process step.

13. A process to provide a biocidal polyurethane-iodine (PU-I) complex, comprising preparing a homogeneous mixture of (i) at least one iodine source and (ii) a thermoplastic polyurethane (TPU) or a polyurethane dispersion (PUD) to form a single-phase system that allows for formation of a biocidal PU-I complex.

14. The process according to claim 13, wherein the at least one iodine source is selected from the group consisting of elemental iodine, polyvinylpyrrolidone-iodine (PVP-I), iodide salts, and combinations thereof.

15. The process according to claim 14, wherein the at least one iodine source is or comprises elemental iodine.

16. The process of claim 13-15, comprising preparing a homogeneous single-phase system by blending at least one iodine source with TPU in a heated, molten or dissolved state.

17. The process of claim 16, comprising dissolving an iodine source in a TPU melt, followed by extrusion.

18. The process of claim 15, comprising adding elemental iodine to an aqueous PUD dispersion and allowing migration of the elemental iodine into the PU phase of the dispersion to obtain a homogeneous single-phase system wherein PU-I complex is formed as an aqueous PU-I dispersion.

19. Process according to claim 18, wherein elemental iodine is added to a PUD as a solution in a suitable solvent that dissolves elemental iodine and is compatible with the PU phase, preferably an alcohol, more preferably isopropanol.

20. Process according to claim 18, wherein elemental iodine is added as solid material, followed by iodine sublimation.

21. The process according to any one of claims 13-20, wherein said TPU or PUD comprises one or more of polyester-based, polyether-based, polycaprolactone-based, polyacrylate-based, aromatic and/or aliphatic thermoplastic polyurethanes.

22. The process according to any one of claims 13-21, wherein TPU or PUD makes up at least 85 weight %, preferably at least 90 weight %, more preferably at least 95 weight % of the total polymer content of the homogeneous mixture of PU and the at least one iodine source.

23. A biocidal polyurethane-iodine (PU-I) complex obtainable by a process according to any one of claims 1-22.

24. The PU-I complex of claim 23, comprising 0.1-10 weight % elemental iodine.

25. The PU-I complex according to claim 23 or 24, comprising 1-30 weight % PVP-I.

26. An aqueous dispersion or a solution comprising a biocidal PU-I complex according to any one of claims 23-24.

27. A biocidal coating comprising or consisting of a PU-I complex according to any one of claims 23-25.

28. Use of a polyurethane-iodine complex according to any one of claims 23-25 in the area of industrial, construction, consumer, pharmaceutical, health, veterinarian and/or aquatic markets.

29. A biocidal product comprising a polyurethane-iodine complex according to any one of claims 23-25.

30. A product provided with a biocidal coating according to claim 27.

31. Product according to claim 29 or 30, selected from the group consisting of air filters, water and solution filters, mouth caps, gloves, equipment or device housing, adhesives, garments, curtains, fibers, hard surface coatings, dentistry articles, building materials, construction materials, carpets, medical devices, wound dressing, tissue scaffolds, operating and endo-scopes, catheters, tubes, breathing tubes, endotracheal tubes, intravascular catheters, deep intravenous lines, footwear, sponges, cutting planks, masks, hoses, food and device packaging, countertops, flexible surface coatings, key boards, upholstery, floor coatings, flooring, condoms, elastics, cardiac valves, pacemakers, mats, mattresses, sealants, breast implants, implants, foams and gaskets.

32. The use according to claim 28, or a product according to claim 29-31, wherein the polyurethane-iodine complex forms a blend, composite and/or interpenetrating network with one or more other natural or synthetic polymers, natural or synthetic fibers, biocidal agents and/or fillers.

Description

LEGEND TO THE FIGURES

[0045] FIG. 1: Schematic representation of exemplary processes for providing biocidal PU-I coatings by adding elemental iodine to an aqueous PU dispersion (PUD). (A) Iodine dissolved in a minimum amount of solvent is mixed with PUD. (B) Iodine added directly to aqueous PU dispersion. (C) Iodine dissolved in an excess amount of solvent is added to PUD. For details see Example 2.

[0046] FIG. 2: Inhibitory effect of exemplary thermoplastic TPU-I filament samples on Staphylococcus aureus growth. For details see Example 4.

[0047] FIG. 3: Inhibitory effect of exemplary thermoset PU-I samples 6, 8 and 11 on (A) Candida albicans and (B) Streptococcus pyrogenes growth. For details see Example 4.

[0048] FIG. 4: Bactericidal effect of exemplary PU-I foams attached inside a human face mask. (A) Control PU Foam plated on growth media showing negligible biocidal activity. (B) PU-I Foam plated on growth media showing significant biocidal activity. For details see Example 5.

EXPERIMENTAL SECTION

EXAMPLE 1: Extrusion Studies with TPU

[0049] 400 Gram extrusion studies were conducted in a Thermo Prism Eurolab 16 twin screw extruder having 16 mm screw diameter and 25 cm barrel length. The extruding barrel had five heating zones that were set at 200° C. The rotation speed of the screws was fixed at 400 rpm.

The raw materials used were an aliphatic polyether-based TPU (Lubrizol TecoFlex™ EG-93A-B30), EP pharmaceutical grade PVP-I (Boai NKY Pharmaceuticals Ltd. KoVidone®-I) and elemental iodine. The TPU was dried and grinded before use. Both PVP-I and elemental iodine were used as received. The powders were dry mixed in a mixer and then fed into the extruder. The extrudate in the form of a molten filament was cooled and pelletized. All extrusion experiments were conducted under a nitrogen atmosphere. The filaments and pellets were used “as is” or formed in sheets for subsequent bacterial growth studies.

TABLE-US-00002 TABLE 1 summary of the various extrusion experiments conducted with TPU. Wt. ratio of Ingredients Biocidal Sample TPU PVP-I Iodine Activity Observations TPU1 100 — — None No biocidal activity TPU2 95 5 — Yes Polymer surface active against Staphylococcus aureus: minimal clearing zone TPU3 92.5 5 2.5 Yes Polymer highly active against Staphylococcus aureus: surface active + large clearing zone

EXAMPLE 2: Producing PU-I Complex Coatings from Aqueous PUD

[0050] This example describes the manufacture of three different PU-I coating systems by adding elemental iodine as an iodine source into an aqueous PU dispersion (PUD). FIG. 3 provides a schematic drawing illustrating for each of the systems the migration of elemental iodine from the continuous phase to the dispersed PU phase to allow for PU-I complex formation.

A) Iodine Dissolved in a Minimum Amount of Solvent.

[0051] A 5% (w/v) aqueous dispersion was prepared of RUCO-COAT EC 4811, which is a water based 32% w/v aliphatic nonionic PUD from Rudolf GmbH. 60 ml of the 5% aqueous solution containing 3 g polymer was stirred and to this dispersion was added 0.03 g elemental iodine dissolved in 2 ml isopropanol. The iodine quickly migrated to the polyurethane phase of the dispersion to generate a PU-I aqueous dispersion. The resultant opaque dispersion was milky brown in appearance and color. Because elemental iodine is not water-soluble, the dissolved iodine concentrates in the PU phase of the aqueous dispersion to generate the resultant PU-I dispersion. The resultant dispersion was stable and easily sprayable to coat desired objects. The final dried PU-I complex contained about 99% PU-1% iodine by weight.

B) Iodine Added Directly to PU Dispersion

[0052] Solid elemental pearled iodine supplied by SQM Europe N. V. was added to the original (32 w/v %) RUCO-COAT EC 4811 aqueous dispersion. The actual amount of iodine added was 2% of the calculated polymer amount in the PUD. The iodine quickly sunk to the bottom of the dispersion to make a multi-phase system. The phases were mixed and the iodine was then allowed to sublime under controlled conditions at 50° C. for 12 hours which resulted in the migration of the elemental iodine to the PU phase of the dispersion to form the PU-I complex. The PU-I dispersion was further diluted with water to give a 17% solids PU-I aqueous dispersion. The resultant opaque dispersion was milky brown in appearance and color. This aqueous dispersion was stable and could be easily sprayed to coat desired objects. The final dried PU-I complex was about 98% PU-2% iodine by weight.

C) Iodine Dissolved in an Excess Amount of Solvent.

[0053] The original 32% aqueous dispersion of RUCO-COAT EC4811 was diluted with an excess of isopropanol solution containing a small amount of dissolved iodine to give a soluble 5% PU-I hydro-alcoholic solution. The resultant light-brown solution was transparent and stable. The final dried complex was about 98.5% PU-1.5% iodine by weight.

Biocidal Testing

[0054] Dispersions A and B and solution C comprising PU-I complex were applied via spray coating onto FFP2 medical face masks—both inside and outside surfaces. The coatings were allowed to dry at room temperature for 1 hr, followed by heated temperature drying at about 60° C. for an additional 30 minutes. The face masks were then worn for 3 hrs by volunteers, removed and the mask surfaces plated on nutrient agar for 24 hrs to observe the level of bacterial growth. All PU-I coatings resulted in a decrease in orally exhaled microbial growth when compared to control FFP2 face mask surfaces having no PU-I coating applied to the surface (data not shown).

EXAMPLE 3: In-Situ PU-I Complex Formation (Polyurethane Thermoset Reactions)

[0055] The following raw materials were used to carry out the PU thermoset reactions: [0056] Hexamethylene diisocyanate (HMDI) [0057] Toluene diisocyanate (TDI) [0058] Polyethylene glycol 400 (PEG) [0059] Glycerol [0060] Polyvinylpyrrolidone K17 (PVP) [0061] 1,4-diazabicyclo[2.2.2]octane (DABCO) [0062] Povidone-iodine (PVP-I) [0063] Elemental iodine (I.sub.2)
The thermoset PU polymerization reactions were conducted by the reaction of an isocyanate with polyethylene glycol/glycerol polyol blend with or without iodine source. If an iodine source was used in the reaction, the iodine was initially dissolved in the polyol blend prior to conducting the polyurethane reaction. Polyurethane reactions including an iodine source required the addition of a catalyst (DABCO) to accelerate the reaction. Without the addition of a catalyst, the polyurethane reactions containing an iodine source failed or required significantly higher curing temperatures and longer reaction times to form the thermoset.

[0064] The polyurethane reaction was conducted by reacting the isocyanate with polyol source at room temperature until homogeneous and the reaction mixture poured into molds and placed in a 60° C. oven for 2 hours. The resultant PU-I thermosets were then tested for biocidal activity. Table 2 presents a summary of the various compositions of polyurethane thermosets tested for biocidal activity.

TABLE-US-00003 TABLE 2 Isocyanate Polyol PVP-I I.sub.2 Catalyst Reaction Sample HMDI TDI PEG/Glycerol PVP Wt % Wt % DABCO Yes No PU2 x x x PU4 x x x x PU6 x x 2.0 x x PU7 x x 0.5 x x PU8 x x 10.0 1.0 x x PU9 x x 1.0 x x PU10 x x x 1.0 x x PU11 x x 3.0 x x PU12 x x 10.0 x x PU16 x x  x.sup.a PU17 x x 10.0 x PU18 x x 0.5 .sup. x.sup.b PU19 x x 0.5 .sup. x.sup.b PU20 x x 10.0 x .sup.aExtremely fast reaction. No time to pour reaction mixture into mold. .sup.bExtremely slow reaction, after elevated temperatures and long reaction times, reaction did take place to some degree.

EXAMPLE 4: Biocidal Activity of PU-I Complexes

[0065] Bacterial testing on thermoplastic TPU-I samples from Example 1 and thermoset PU-I samples from Example 3 were conducted as follows: Staphylococcus aureus, Staphylococcus epidermis, Streptococcus pyrogenes and Candida albicans were grown in tryptic soy broth (TSB) overnight at 37° C. 100 μl of the overnight cultures were diluted to an optical density at 600 nm (OD.sub.600) of 0.1 and subsequently plated on 100 mm Mueller-Hinton agar plates (MHA). TPU extruded filaments and PU thermosets were placed on top of the plates, and the plates were then incubated at 37° C. Growth inhibition was inspected at 24 and 48 h of incubation.
Exemplary TPU samples TPU2 and TPU3 showed biocidal activity versus S. aureus as shown in FIG. 2. Sample TPU3 containing 3 weight % iodine showed a significant clearing zone. Sample TPU2 containing 0.5 weight % iodine showed a significantly smaller clearing zone while the starting TPU1 sample showed no biocidal activity.
Exemplary PU samples PU6, PU8 and PU11 were highly active against S. aureus, S. epidermis, C. albicans and S. pyrogenes, showing defined clearing zones for all microorganisms tested. FIG. 3 shows the resultant clearing zones with respect to C. albicans and S. pyrogenes inhibition. Thermoset PU samples containing lower levels of iodine seem to be surface biocidal, but do not show the defined clearing zones as PU samples 6, 8 and 11. PU samples containing no iodine source were not biocidal.

EXAMPLE 5: Manufacture and Biocidal Activity of PU-I Thermoset Foams

[0066] The following 3 PU-I foam systems were prepared and evaluated for biocidal (bactericidal and antiviral) activity.

TABLE-US-00004 Elemental Polyol/Chain Iodine Reaction Sample Isocyanate* extender (wt. %) Details PU21 MDI Polyester Polyol 0.5 Iodine (CAS 28183-09-7) dissolved in diol chain extender, surfactant and tertiary amine catalyst phase PU22 MDI Polyether 1.6 Iodine Polyol Mixture dissolved in (CAS 9082-00-2 diol chain and CAS extender, 68650-94-2) surfactant and tertiary amine catalyst phase PU23 MDI Polyether 0.5 Iodine Polyol Mixture dissolved in (CAS 9082-00-2 diol chain and CAS extender, 68650-94-2) surfactant and tertiary amine catalyst phase *MDI (Methylene diphenyl diisocyanate)
The PU21 sample foam was subsequently reticulated to form an open structure foam that could be used as a filter. Foams PU22 and PU23 were not reticulated.

Bactericidal Testing:

[0067] The reticulated PU21 foam sample was cut into 2 mm thick sheets that were further cut to shape to fit into a standard face mask. The PU21 foam was fastened to the inner side of the face mask and worn by a human volunteer for a period of 3 hours. The foam was then removed and plated on growth media overnight and the bacterial colonies observed. The same test was also conducted using a similar reticulated PU foam that contained no PU-I complex. FIG. 4 shows representative photos of the bacterial growth colonies for common PU reticulated foam and the PU21 PU-I complex foam. It demonstrates that the PU-I complex foam of the invention is highly biocidal against exhaled microorganisms.

Antiviral Testing:

[0068] The antiviral activity was determined by adding a known amount of SARS-CoV-2 virus stock to the various foam samples (PU21-PU23). The virus stock was allowed to be in contact with the foam for the desired time period and then the viral supernatants were removed from the foam and titered onto 10,000 Vero E6 cells to quantitatively determine the viral titer reduction. PU foams with no iodine addition and no foam system were used as controls. Samples PU21, PU22 and PU23 showed significant viricidal activity against the SARS-CoV-2 virus. The three samples showed a minimum of 90% virus reduction at contact times of 10 minutes when compared against the control foam and no foam controls, and a minimum 99% virus reduction for 12 hours contact times.
A summary of the biocidal and antiviral properties is provided in the following table.

TABLE-US-00005 SARS-CoV-2 SARS-CoV-2 Exhaled Viral Titer Viral Titer oral Reduction vs Reduction vs Sample Foam bacteria control foam** (%) no foam** (%) PU21 Reticulated Highly 99.9/99.9 99.9/99.0 biocidal PU22 Non- Not tested .sup. 99/99.9 99.0/99.0 reticulated PU23 Non- Not tested 90.0/99.9 .sup. 99/99.0 reticulated **contact times 10 minutes/12 hours

EXAMPLE 6: Difference Between Adding PVP-I as Dispersion or as Solution

[0069] This example provides comparative test results between PU foams prepared by adding PVP-I to the PU polymerization mixture either in the form of a dry powder (e.g. similar to U.S. Pat. No. 5,302,392) or as a solution in a raw material of the PU reaction (according to the in-situ process of the invention).

[0070] Two identical PU reactions were conducted in which the PVP-I was added as a powder or solution. The details are shown in the table below.

TABLE-US-00006 PVP-I Sample Isocyanate* Polyol System (wt. %) PVP-I 1 MDI Polyester 5 Added as dry Polyol/diol powder 2 MDI Polyester 5 Added as solution Polyol/diol *MDI (methylene diphenyl diisocyanate
Sample 1 was performed in accordance with U.S. Pat. No. 5,302,392 (see Example I). PVP-I powder was quickly dispersed in the polyester polyol to generate a uniform slurry of PVP-I powder in the polyol. Subsequently, the isocyanate MDI was added to initiate the polyurethane reaction. As expected, this reaction proceeded quickly to generate a PU foam in which the PVP-I complex powder was entrapped in the PU foam matrix. The PU reaction was not affected by the addition of the PVP-I powder because the PVP-I did not dissolve to any significant amount into the polyol and thus did not inhibit the polyurethane reaction. Consistent with the teaching of U.S. Pat. No. 5,302,392, the resultant product consisted primarily of PVP-I particles dispersed/entrapped in a PU foam matrix.
In the PVP-I solution reaction (sample 2), PVP-I was first dissolved in the chain extender diol to give a PVP-I solution. This single phase solution was mixed with the polyol to generate a polyol/diol PVP-I solution. The subsequent polyurethane reaction with MDI was conducted under the same reaction conditions as sample 1. However, this reaction was completely inhibited. Only after the addition of a significant amount of catalyst did the reaction proceed to give the homogeneous 1-phase PU-I complex foam.
As an additional control, a reaction was conducted in which PVP homopolymer (no iodine present) was dissolved in the chain extender diol to give a soluble PVP solution. The PVP solution was added to the polyol and the polyurethane reaction was conducted with MDI as in previous experiments. The polyurethane reaction proceeded as normal and was not inhibited, showing that the inhibition of the polyurethane reaction is caused by the iodine species.