WO2022219645A1

WO2022219645A1 - Anti microbial additive compositions and methods of preparation

Info

Publication number: WO2022219645A1
Application number: PCT/IN2022/050353
Authority: WO
Inventors: Prerna Goradia
Original assignee: Prerna Goradia
Priority date: 2021-04-15
Filing date: 2022-04-12
Publication date: 2022-10-20

Abstract

The present invention relates to non-cytotoxic bulk antimicrobial composition for manufacturing anti microbial composites such as plastic, glass, ceramic, bio-degradable materials etc. and method of preparing the same. The heat and light stable, broad spectrum composition provides long-term protection against a large number of gram-positive / gram-negative bacteria, yeast, fungi and algae. It disrupts the metabolic process of unwanted micro-organisms and thus interrupts their ability to function, grow and proliferate. The technology involves the microbe-killing properties of transition metal compounds, based on enzyme and cell wall killing of the microbes by the slow release of ionic material. The combination of the antimicrobial property with mechanical strength and barrier property enhancement is also reported.

Description

ANTI MICROBIAL ADDITIVE COMPOSITIONS AND METHODS OF PREPARATION

FIELD OF THE INVENTION:

[001] The present invention broadly relates to anti microbials. More particularly, the invention relates to non-cytotoxic antimicrobial additive compositions for bulk incorporation into materials such as plastics/ceramic/glass/composites/ concrete/asphalt and a method for manufacturing the antimicrobial composite. The bulk antimicrobial fillers consist of thermally stable ceramic materials.

BACKGROUND OF THE INVENTION

[002] In daily life, microbes exist on the surface of articles such as plastic, glass, and ceramic; proliferate and are in turn causative agents of various diseases. Thus, there is a need to control the growth and survival of microorganisms like gram- positive / gram-negative bacteria, yeast, fungi and algae etc. In particular, it is often necessary to limit the number or to maintain that there is absence of microorganisms or species in that particular zone. This is very much required in households, medical and pharmaceutical products; constructed spaces etc. To address this problem of limiting microbes, research has been done to impart the antimicrobial properties to a variety of plastic, glass and glass-ceramic type of articles.

[003] Since ancient times, it has been known that metal and ions of metals such as mercury, silver, copper, zinc show antimicrobial activity. The bactericidal mechanism of such metals differs from that of antibiotics. It is acknowledged that copper, silver and other anti microbial metals are effective to inhibit growth of various microorganisms and these microorganisms never acquire resistance to the bactericidal metals.

[004] But there are shortcomings such as poor durability of antimicrobial activity, use safety, poor heat resistance, toxicity, and narrow range of application. [005] References have been made to the following literature:

[006] KR100801229 relates to a method for producing antimicrobial plastic having excellent adhesion of silver nanoparticles to an adherend, in particular to a polymer resin, and accordingly, when silver nanoparticles prepared by electrolysis are deposited on a polymer resin for at least two years. Bare silver nanoparticles are not heat or often times light stable whereas the present invention is a combination of different refractory metal oxides and salts with high temperature stability of > 500 C, making it a heat and light stable composition.

[007] Review by Ewa Karwowska discusses about the antibacterial potential of nanocomposite-based materials. Besides, the biocidal or bacteriostatic properties of nano-scaled materials such as fabrics, plastics and metal coated with nano- silver as well as nanocomponents based on titanium dioxide, magnesium oxide, copper and copper oxide, zinc oxide, cadmium selenide/telluride, chitosan and carbon nanotubes have been reported. The prior art discusses about nanomaterial and coating of materials whereas the present invention involves a stable ceramic mixture, added to the composites.

[008] EP0333118A1 relates to antimicrobial powders obtained by supporting at least one antimicrobial metal of copper, zinc and alloys thereof on the surface of hydrous titanium oxide or titanium oxide particles by electroless plating, vapor deposition, compression mixing, mixing and reducing, and thermal decomposition of compound. The powders are used to provide antimicrobial resin compositions, antimicrobial rubber compositions, antimicrobial glass compositions and antimicrobial coating compositions. The prior art states about coating the oxide particles with the metal, whereas the present invention involves a different composition and discusses about a mass manufacturable process.

[009] US20050233888A relates to an antimicrobial phosphate glass composition that comprises the following components in wt % based on oxide of P₂O₅>45-90 wt %, K₂O 0-0.1 wt %, BaO 0-40 wt %, ZnO 0-40 wt %, Ag₂O 0-5 wt % and CuO 0-15 wt %. This relates to an antimicrobial phosphate glass composition, whereas the present invention relates to an antimicrobial additive composition which needs to be added as a last step into the composite.

[0010] US20160229743 discloses glass, ceramic, or glass-ceramic articles having improved antimicrobial efficacy and methods of making and using the improved articles. The improved articles generally include a glass, ceramic, or glass-ceramic substrate, and an antimicrobial agent-containing region that extends inward from the surface of the glass, ceramic, or glass-ceramic substrate to a second depth therein. The prior art discusses about coating the articles with the antimicrobial agent in turn rendering the antimicrobial property for a short duration only whereas the present invention involves a stable ceramic mixture, which as embedded into the composites gives a stable and long term activity.

[0011] It is evident that despite the widespread use of copper and silver nanoparticles, they have a limited durability and there are chances of leaching of the toxic chemicals. Moreover, the increasing concern about resistant microorganisms stimulates the study of new and more effective antimicrobial agents. The present invention relates to provide a heat and light stable antimicrobial additive composition with broad spectrum activity against pathogens and low toxicity in non-aqueous based applications. Besides, the methodology involved in the present invention is a unique and manufacturable solution, where the additive being added in the end step in the composite, results in the slow release of active ions in the composite and thus in turn leading to prolonged protection against pathogens.

[0012] The information disclosed in this background of the disclosure section is only for enhancement of understanding of the general background of the invention and should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art already known to a person skilled in the art. SUMMARY OF THE INVENTION:

[0013] The present invention attempts to overcome the problems faced in the prior art, and discloses a composition which can effectively neutralize microorganisms while not altering the characteristics of future formulations/composites by providing for a stabilized, non-toxic, antimicrobial composite article.

[0014] The present invention discloses non-cytotoxic antimicrobial composition for manufacturing anti microbial composites such as plastic, glass, ceramic etc. and method of preparing the same. The composition comprises of titania, silica, silver, zinc and copper where the combination of these transition metals results in a synergistic antimicrobial action, very important for providing the distinct property to the composites.

[0015] The present invention relates to an anti-microbial additive composition including at least a transition metal compound 0.01- 10% (wt/v) and at least a delivery particle 90-99.9 % (wt/v). In an embodiment, the invention discloses an additive where at least one transition metal compound is selected from a group comprising copper, zinc, silver, gold, tungsten, titanium, ruthenium and alloys and combinations thereof. The transition metal compound is selected from a group comprising sliver chloride, zinc oxide, copper salts, metal nitrides, metal carbides, salts mixed with metal oxides such as CU₂O, CuO, ZnO, SiO2, T1O₂, and WO₃ and combinations thereof.

[0016] The present invention discloses an additive where the delivery particle is selected from a group comprising titania, silica, hydrous titanium oxide, titanium oxide, or zeolites such as zeolites (microporous, aluminosilicate minerals) and combinations thereof.

[0017] The present invention relates to a method for producing antimicrobial additive composition for composites comprising the steps: (a) mixing at least one or a mixture of antimicrobial metal compound selected from the group consisting of copper, zinc, silver, gold, tungsten, titanium, ruthenium and alloys and combinations thereof with carrier particle in range of 0.01-10% (w/v); (b) grinding the powders from step (a) together into micro fine form using industrial grinder and ball-milling procedures as well at high-temperatures (up to 700° C); followed by sintering to stabilize the powders; preparing a master batch by a compounding procedure involving mixing of the powder obtained in step (c) with a resin and or a binder and passing the composition through a twin screw extruder, wherein the mixture melts in the form of a homogeneous thread/string, followed by cooling and making pellets in turn forming the masterbatch; mixing the master batch with the compound/article to form the antimicrobial composite.

[0018] The present invention relates to a method where the carrier particle for supporting the antimicrobial metal on the surface of the particles is selected from a group consisting of hydrous titanium oxide or titanium oxide or silica or zeolites such as zeolites (microporous, aluminosilicate minerals) and combinations thereof but not limited to. The ball and milling process is incorporated in the method for generating the particles of the size > 4 micron so that the particle is not of inhalable size. Further, sintering involves diffusion of the atoms in materials across the particle boundaries and fusing together into one piece.

[0019] The present invention discloses a method where the binder or resin is typically of same material which is of the article and is selected from a group consisting of polymer, high boiling point liquid polymer, surfactant and combinations thereof but not limited to.

[0020] The present invention further discloses an antimicrobial composition to prohibit the growth of microorganisms, prevent unpleasant odors, discoloration, and surface degradation of the article. The resultant formulation is non-toxic, safe for skin & food products, non-caustic and does not contain any heavy metals or arsenic. The composition besides being broad spectrum and stable, formulates well with other compounds, thereby enabling safe usage on food grade and medical fields, without any adverse side effects. Further, the composition is in powdered form or a liquid form with high boiling liquid additive. [0021] The foregoing summary is illustrative only and is not intended to be in any way limiting. In addition to the illustrative aspects, embodiments, and features described above, further aspects, embodiments, and features will become apparent by reference to the drawings and the following detailed description.

DESCRIPTION OF THE PREFERRED EMBODIMENTS:

[0022] While the embodiments of the disclosure are subject to various modifications and alternative forms, specific embodiments thereof have been shown by way of example in the figures and will be described below. It should be understood, however, that it is not intended to limit the disclosure to the particular forms disclosed, but on the contrary, the disclosure is intended to cover all modifications, equivalents, and alternatives falling within the scope of the disclosure. Further, the phraseology and terminology employed in the description is for the purpose of description only and not for the purpose of limitation.

[0023] The terms “comprises”, “comprising”, or any other variations thereof used in the disclosure, are intended to cover a non-exclusive inclusion, such that a device, apparatus, system, assembly, method that comprises a list of components or a series of steps that does not include only those components or steps but may include other components or steps not expressly listed or inherent to such apparatus, or assembly, or device. In other words, one or more elements or steps in a system or device or process proceeded by “comprises... a” or “comprising of’ does not, without more constraints, preclude the existence of other elements or additional elements or additional steps in the system or device or process as the case may be.

[0024] The present invention relates to non cytotoxic antimicrobial composition for manufacturing anti microbial composites such as plastic, glass, ceramic etc. and method of preparing the same. The heat and light stable, broad spectrum composition provides long-term protection against a large number of gram- positive / gram-negative bacteria, yeast, fungi and algae. It disrupts the metabolic process of unwanted micro-organisms and thus interrupts their ability to function, grow and proliferate.

[0025] The invention further relates to antimicrobial effects from silver chloride and copper salts mixed with metal oxides such as CU₂O, CuO, ZnO, T1O₂, and WO_3. The technology involves the microbe -killing properties of silver, based on enzyme and cell wall killing of the microbes by the slow release of ionic material. Further, the mechanism referred to the antimicrobial action of titania is commonly associated to reactive oxygen species (ROS) with high oxidative potentials produced under band-gap irradiation photo-induces charge in the presence of O₂. ROS affect bacterial cells by different mechanisms leading to their death. Also, the mechanism of action of ZnO is also thought to involve the production of reactive oxygen species, which elevates membrane lipid peroxidation that causes membrane leakage of reducing sugars, DNA, proteins, and reduces cell viability. The main antimicrobial mechanism of the composition has been attributed to the induction of oxidative stress due to the formation of reactive oxygen species, membrane disruption due to the accumulation of ZnO therein, and internalization of nanoparticles followed by the release of antimicrobial ions (Zn⁺²).

[0026] In an embodiment, the present invention relates to an anti-microbial additive composition including at least a transition metal compound 0.01- 10% (wt/v) and at least a delivery particle 90-99.9 % (wt/v).

[0027] In another embodiment, the present invention discloses an additive where at least one transition metal compound is selected from a group comprising copper, zinc, silver, gold, tungsten, titanium, ruthenium and alloys and combinations thereof. The transition metal compound is selected from a group comprising sliver chloride, zinc oxide, copper salts, metal nitrides, metal carbides, salts mixed with metal oxides such as CU₂O, CuO, ZnO, SiO2, T1O₂, and WO₃ and combinations thereof. [0028] In another embodiment, the present invention discloses an additive where the delivery particle is selected from a group comprising titania, silica, hydrous titanium oxide, titanium oxide, or zeolites such as zeolites (microporous, aluminosilicate minerals) and combinations thereof.

[0029] In an exemplary embodiment, the present invention discloses a method for producing antimicrobial additive composition for composites comprising the steps: (a) mixing at least one or a mixture of antimicrobial metal compound selected from the group consisting of copper, zinc, silver, gold, tungsten, titanium, ruthenium and alloys and combinations thereof with carrier particle in range of 0.01-10% (w/v); (b) grinding the powders from step (a) together into micro fine form using industrial grinder and ball-milling procedures as well at high- temperatures (up to 700° C); followed by sintering to stabilize the powders; preparing a master batch by a compounding procedure involving mixing of the powder obtained in step (c) with a resin and or a binder and passing the composition through a twin screw extruder, wherein the mixture melts in the form of a homogeneous thread/string, followed by cooling and making pellets in turn forming the masterbatch; mixing the master batch with the compound/article to form the antimicrobial composite.

[0030] In another embodiment of the present invention the carrier particle for supporting the antimicrobial metal on the surface of the particles is selected from a group consisting of hydrous titanium oxide or titanium oxide or silica or zeolites such as zeolites (microporous, aluminosilicate minerals) and combinations thereof but not limited to.

[0031] In a preferred embodiment, the present invention discloses a method for producing antimicrobial additive composition for composites where the ball and milling process is incorporated for generating the particles of the size > 4 micron so that the particle is not of inhalable size. [0032] In another preferred embodiment, the present invention discloses a method where the sintering involves diffusion of the atoms in materials across the particle boundaries and fusing together into one piece.

[0033] In yet another embodiment, the present invention discloses a method where the binder or resin is typically of same material which is of the article and is selected from a group consisting of polymer, high boiling point liquid polymer, surfactant and combinations thereof but not limited to.

[0034] In still another embodiment, the present invention discloses a composition where the composition is in powdered form or a liquid form with high boiling liquid additive.

[0035] Examples: The anti microbial effectiveness of the composites against Staphyloccus aureus and Pseudomonas aeruginosa was checked by ASTM E2180 - 18 methods. ASTM E2180 - 18 is a standard test method for determining the activity of incorporated antimicrobial agent(s) in polymeric or hydrophobic materials.

[0036] Example 1: In Sample PP-MF650Y, polypropylene plastic powder (PP) was mixed in the master-batch with 2% antimicrobial additive composition comprising of silver chloride and titania (2% silver chloride mixed with 98% titania) at a concentration of 2%Wt/Vol. The mixture was subjected to normal plastic manufacturing processes consisting of melting, extrusion and pelleting steps. The test sample showed 96.9% reduction against Staphyloccus aureus and 90% reduction against Pseudomonas aeruginosa as compared to reference sample after 2 hours. As can be understood, the reference is the sample where the addition of antimicrobials had not been done (Table 1). [0037] Table 1: Antimicrobial activity against Staphyloccus aureus and Pseudomonas aeruginosa

[0038] Example 2: In sample ABS-MG47F, Acrylonitrile butadiene styrene (ABS) plastic material was mixed with 3% antimicrobial additive composition of silver chloride and titania (3% silver chloride mixed with 96.5% titania) and 0.5% zinc oxide powder was also added. ABS being a complicated plastic material in terms of composition, zinc was added to the additive and the test sample showed 91.11 % reduction against Staphylococcus aureus as compared to reference sample after 2 hours (Table 2).

[0039] Table 2: Antimicrobial activity against Staphyloccus aureus

[0040] Example 3: In Sample PP-H110MA, polypropylene plastic was mixed in the manufacturing process with 3% antimicrobial additive composition comprising of silver chloride and titania (3% silver chloride mixed with 97% titania). The test sample showed 99.54 % reduction against Staphylococcus aureus as compared to reference sample after 8 hours. The results confirm the stable anti microbial effectiveness of the additive over a period of time (Table 3).

[0041] Table 3: Antimicrobial activity against Staphyloccus aureus after 8 hours of treatment.

[0042] Example 4: Accelerated Ageing Study: The composite (Sample PP- H110MA) was subjected to accelerated ageing testing·. The method employed testing of the device or material at high stress for a short period of time in order to deduce the dominant failure mode. A simplified approach for accelerated aging was based on conducting testing at a single accelerated temperature and then employing the rule stating that the rate of a chemical reaction would increase by a factor Qio for every 10^°C increase in temperature. The typical relationship selected for commonly used medical polymers was Qio = 2 — that is, a doubling of the reaction rate for each 10°C increase in the temperature above the use or storage temperature. The simplified protocol for accelerated shelf-life testing was not a replacement for a more complex and advanced accelerated-aging protocol, but instead a protocol for systems known to conform to zero, first -order Arrhenius behavior. This type of conservative relationship was appropriate for a wide range of medical polymers that have been previously characterized (Table 4 & Table 5). [0043] Table 4: Quantitative Assessment of Antimicrobial Activity of the article before ageing

[0044] The accelerated aging piece was subjected to + 70 °C and RT for 100 cycles ASTM D3045 (Table 5).

[0045] Table 5: Quantitative Assessment of Antimicrobial Activity of the article after the ageing process

[0046] Further, the similar accelerated ageing treatment was given for different types of composites to test the stability of the antimicrobial activity of the additive composition in the composites. It was observed that different types of composites retained the antimicrobial activity even after 24 hours of accelerated ageing process. But since ABS material in itself has some antimicrobial property, thus the control samples also retained the antimicrobial activity after the accelerated ageing treatment (Table 6).

[0047] Table 6: The results for the different type of plastics are as under

[0048] Example 5: In yet another important set of experiments - high refractory silver salt such as silver chloride was mixed directly into PET powder of viscosity around 0.8. The powder was then used to make a master batch and then the master batch was used to make the finished goods by molding process. The results are extremely promising and yield a good antimicrobial ability.

[0049] Example 6: Leachate Study: The important leachate study was also undertaken to study the migration ability of the test solutions. The leaching of the transition metals from the antimicrobial composition treated samples was recorded by the Absorption Spectroscopy. It was observed that there was no leaching of zinc and silver ions in the medium, thus making these antimicrobial additive comprising composites as food safe grade (Table 7).

[0050] Table 7: Analysis report of the samples by Absorption Spectroscopy:

[0051] Example 7: Testing on compostable: In this experiment antimicrobial additive composition was added to the starch containing plastic bags. Since starch in itself is a substrate for the microbes to grow, antimicrobial activity was checked on the surface of Bio waste plastic Bag for antimicrobial effectiveness against Staphylococcus aureus. In the test method ISO 22196-2011, SCDLP Broth was used as a Neutralizer, for a contact time of 24 h at 35 °C and the results are represented in Table 8, where the treated samples 98.6% microbial reduction as compared to the untreated control samples. [0052] Table 8: Antimicrobial activity on compostable

[0053] In accordance with advantages of the present invention as compared with the existing formulations, the present invention is to provide a big change in the field of antimicrobial composites. The composition, with low toxicity and non- sensitizing nature, is effective at very low ppm addition levels. The microbial composition is to be added as a single and last component, without the need of any binders to the plastic melt, thus not interfering with the characteristics of future composite compositions. Further materials such as graphene with the representative spectral features and also silicates were used to enhance the antimicrobial, barrier and mechanical properties all at once. Specifically, the relatively high molecular weight molecule tetrakis (2-ethyl hexyl) orthosilicate was used along with small quantities of pure silica. Other materials such as glass fiber, boron nitride nanoparticles, carbon fibers and silicon carbide can also be used. [0054] Advantages:

• Additives retard microbe growth in finished plastic parts, in turn enhancing product performance

• Reduces bacterial, mold and fungal growth on the surface as well as through the thickness of the plastic part

• Helps reduce odor, staining, discoloration and loss of mechanical properties

• Available for a variety of processes including extrusion, injection molding, blow molding, rotational molding and thermoforming

• Multiple antimicrobial formulation types available; customizable based on specific requirements

• Inorganic stable compositions which act as permanent additive in different types of plastics

[0055] It will be further appreciated that functions or structures of a plurality of components or steps may be combined into a single component or step, or the functions or structures of one-step or component may be split among plural steps or components. The present invention contemplates all of these combinations. Unless stated otherwise, dimensions and geometries of the various structures depicted herein are not intended to be restrictive of the invention, and other dimensions or geometries are possible. In addition, while a feature of the present invention may have been described in the context of only one of the illustrated embodiments, such feature may be combined with one or more other features of other embodiments, for any given application. It will also be appreciated from the above that the fabrication of the unique structures herein and the operation thereof also constitute methods in accordance with the present invention. The present invention also encompasses intermediate and end products resulting from the practice of the methods herein. The use of “comprising” or “including” also contemplates embodiments that “consist essentially of’ or “consist of’ the recited feature.

[0056] Although embodiments for the present invention have been described in language specific to structural features, it is to be understood that the present invention is not necessarily limited to the specific features described. Rather, the specific features and methods are disclosed as embodiments for the present invention. Numerous modifications and adaptations of the system/component of the present invention will be apparent to those skilled in the art, and thus it is intended by the appended claims to cover all such modifications and adaptations which fall within the scope of the present invention.

Claims

CLAIMS,

1. An anti-microbial additive composition comprising: at least a transition metal compound 0.01- 10% (wt/v); and at least a delivery particle 90-99.9 % (wt/v).

2. The additive composition as claimed in claim 1, wherein at least one transition metal compound is selected from a group comprising copper, zinc, silver, gold, tungsten, titanium, ruthenium and alloys and combinations thereof.

3. The additive composition as claimed in claim 2, wherein the transition metal compound is selected from a group comprising sliver chloride, zinc oxide, copper salts, metal nitrides, metal carbides, salts mixed with metal oxides such as CU₂O, CuO, ZnO, SiO2, T1O₂, and WO₃ and combinations thereof.

4. The additive composition as claimed in claim 1, wherein the delivery particle is selected from a group comprising titania, silica, hydrous titanium oxide, titanium oxide, or zeolites such as zeolites (microporous, aluminosilicate minerals) and combinations thereof.

5. A method for producing antimicrobial additive composition for composites comprising the steps: a. mixing at least one or a mixture of antimicrobial metal compound selected from the group consisting of copper, zinc, silver, gold, tungsten, titanium, ruthenium and alloys and combinations thereof with carrier particle in range of 0.01-10% (w/v) b. grinding the powders from step (a) together into micro fine form using industrial grinder and ball-milling procedures as well at high- temperatures (up to 700° C); c. followed by sintering to stabilize the powders; d. preparing a master batch by a compounding procedure involving mixing of the powder obtained in step (c) with a resin and or a binder and passing the composition through a twin screw extruder, wherein the mixture melts in the form of a homogeneous thread/string, followed by cooling and making pellets in turn forming the masterbatch; e. mixing the master batch with the compound/article to form the antimicrobial composite.

6. The method for producing antimicrobial additive composition for composites as claimed in claim 5, wherein the carrier particle for supporting the antimicrobial metal on the surface of the particles is selected from a group consisting of hydrous titanium oxide or titanium oxide or silica or zeolites such as zeolites (microporous, aluminosilicate minerals) and combinations thereof but not limited to.

7. The method for producing antimicrobial additive composition for composites as claimed in claim 5, wherein ball and milling process is incorporated for generating the particles of the size > 4 micron so that the particle is not of inhalable size.

8. The method for producing antimicrobial additive composition for composites as claimed in claim 5, wherein sintering involves diffusion of the atoms in materials across the particle boundaries and fusing together into one piece.

9. The method for producing antimicrobial additive composition for composites as claimed in claim 5, wherein the binder or resin is typically of same material which is of the article and is selected from a group consisting of polymer, high boiling point liquid polymer, surfactant and combinations thereof but not limited to.

10. The anti-microbial additive composition as claimed in claim 1 or 5, wherein the composition is in powdered form or a liquid form with high boiling liquid additive.