Conformation modified polymers with pathogen inactivation configurations

Abstract

The embodiment is a morphologically active polymer comprising at least one pathogen binding site and where the morphologically active polymer, after binding the pathogen, changes at least its morphology, conformation, or configuration and inactivates the pathogen.

Description

[0001] Atty Dkt No.: IPAC-011WO CONFORMATION MODIFIED POLYMERS WITH PATHOGEN INACTIVATION CONFIGURATIONS CROSS-REFERENCE TO RELATED APPLICATIONS [1] This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 538,609, titled “Conformation Modified Polymers with Pathogen Inactivation Configurations,” which was filed on September 15, 2023, the disclosure of which is incorporated by reference herein in its entirety. BACKGROUND [2] The stereochemistry of polymers is an important aspect of the polymer’s characteristics and the effects that polymers may have on other materials, organisms, and systems. [3] Prions are examples of the mis-folding conformation of protein molecules. The folding of the prion protein molecules is mis-folded and induces proteinopathy or protein mis-folding disease. Proteinopathies include such diseases as Creutzfeldt- Jacob disease (CJD) and bovine spongiform encephalopathy (BSE), also known as mad cow disease. [4] Both cellulose and starch are polysaccharides and have the same chemical constituents. The difference between the molecules is that cellulose has a beta bond while starch has an alpha bond. Both molecules are composed of glucose monomers as shown in Fig. 3. However, the 1-4 linkage of the alpha (α) glucose monomers is different from the 1-4 linkage of the beta (β) glucose monomers. An α bond has the hydroxyl groups in the same orientation from glucose monomer to glucose monomer while a β bond has hydroxyl groups in the opposite orientation from glucose monomer to glucose monomer. As a result, starch is digestible by humans while cellulose is not. Thus, another example where the conformation of molecules may have very different characteristics. [5] Protein conformational switches are polypeptides that undergo a significant change in structure upon receiving an input signal. Input stimuli can consist of covalent modifications, such as phosphorylation or cleavage of the polypeptide backbone, or more commonly, molecular recognition events. Examples of the last type include Page 1 of 12 ACTIVE / 124931401.1 Atty Dkt No.: IPAC-011WO absorbing a photon, binding a drug, or engaging an entire cell via a surface receptor. The resulting conformational change establishes the output response. For instance, the structural change may modulate enzymatic activity or expose new surface for the protein to interact with other molecules. Many proteins bind other molecules and / or become covalently modified; however, it is the property of stimulus-induced structural change that defines the more select cohort of conformational switches. [6] Both the molecular conformation of a polymer and the morphology of a polymer may have positive or deleterious effects in various and different environments. Specialty polymers are sought that have pathogen inactivating characteristics either from a molecular conformational difference and / or a morphological difference. SUMMARY [7] The embodiment is the use of morphologically active polymers (MAPs) which act with a pathogen inactivating process either as produced or by changing in response to a stimulus. The stimulus may be the act of binding of a chemical compound to the MAP. The morphologically active polymers may be different in molecular conformation and / or morphological configuration. A further embodiment comprises molecular configuration of the polymer where the molecular configuration disrupts the lipid bilayer of enveloped or nonenveloped viruses and inactivates the virus. [8] Yet a further embodiment incorporates molecular configurations of polymers, the arrangements of molecules that are bonded to one another, where the molecular configurations inactivate pathogens and where the polymers incorporate moieties that allow for the inactivation of pathogens. [9] Further still, the embodiment is the conformation of the polymer, the ability of monomers within a polymer chain to rotate about a single bond and thus alter the shape, size and features of the polymer as a whole. Here, the altered polymer is due to the influence of a pathogen binding to the polymer chain and altering the conformation of the polymer.

[0010] An example of the embodiment is a certain class of polymers that incorporates both organic and inorganic components and moieties to form a specialty polymer. Page 2 of 12 ACTIVE / 124931401.1 Atty Dkt No.: IPAC-011WO Commonly referred to as ionomers, the specialty polymeric materials are typically comprised of olefinic polymer chains, typically ethylenic in nature, and unsaturated acids and where some of the unsaturated acid groups are neutralized with metal cations.

[0011] Ionomers may be formed of the various types of materials such as plastic plaques or plastic fibers. One type of plan number is a sulfonated tetrachloroethylene known under the tradename of Nafion®. Nafion®is utilized in many unique applications including a proton exchange membrane for fuel cells, chlor-alkali production membranes, and the desalination of water.

[0012] The annealing effect on polymers such as polyethylene is indicative of a morphological change of the polymer due to external forces. When polyethylene is injection molded, for instance, at high temperature and cooled quickly to be removed from a mold, micro and nano crystalline structures are formed in the polymer matrix. Through the process of annealing the polymer, i.e. heating the polymer and then slowly cooling it, the crystalline structures change in nature and thus change the physical properties of the polyethylene polymer. Such physical changes include the surface energy of the polymer.

[0013] The morphologically active polymer may also be configured to be an ablative or sacrificial polymer. With the incorporation of the ablative or sacrificial polymer and pathogen inactivating material, pathogens such as pathogenic bacteria, viruses, fungi, protozoa, and worms are inactivated and rendered harmless for infection.

[0014] The morphologically active polymer with ablative or sacrificial characteristics is configured to allow the surface of the polymer or the bulk of the polymer to wear down with time, exposing a new fresh surface of the polymer where the ablative polymer is concerned or a bulk breakdown of the polymer where a sacrificial polymer is concerned. This breakdown of the ablative or sacrificial polymer will expose fresh pathogen inactivating material to the environment. This morphological change in the polymer will also change the surface tension of the polymeric material and thus change its interaction with the macroenvironment. Page 3 of 12 ACTIVE / 124931401.1 Atty Dkt No.: IPAC-011WO

[0015] The ablative, sacrificial and / or morphologically active polymer may be an emulsion polymer. The emulsion polymer may be a nonionic, cationic, or anionic emulsion polymer.

[0016] Further configurations of morphologically active polymers are considered for both their ability to inactivate pathogens and to bind pathogens to the polymer structure. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The foregoing aspects and other features of the disclosed embodiments are explained in the following description, taken in connection with the accompanying drawings, wherein:

[0018] Figure 1 illustrates the morphological enantiomer differences between cumin and spearmint.

[0019] Figure 2 illustrates a properly folded protein mis-folded protein is a prion.

[0020] Figure 3 illustrates the differences between starch and cellulose as an alpha or beta bond respectively.

[0021] Figure 4 illustrates the exfoliation of a polymer.

[0022] Figure 5 is the stereo conformation of heparin.

[0023] Figure 6 is the stereo conformation of various polysaccharides.

[0024] Figure 7 is a stereo conformation of an ethylene acid copolymer.

[0025] Figure 8 is the stereo conformation of a partially neutralized ethylene acid copolymer where the neutralizing agent is silver.

[0026] Figure 9 is perforated polymeric film.

[0027] Figure 10 is perforated polymeric film. Page 4 of 12 ACTIVE / 124931401.1 Atty Dkt No.: IPAC-011WO DETAILED DESCRIPTION

[0028] The embodiments herein describe the use of morphologically active polymers (MAPs) which act with a pathogen inactivating process either as produced or by changing in response to a stimulus, the stimulus typically caused by a pathogen.

[0029] The embodiments described herein also disclose a polymer where the polymer contains an agent, such as a pathogen inactivating material, for inactivating viruses, bacteria, and fungi. Specifically, the biocide in the polymer is used to inactivate the SARS–CoV–2 virus causing the Covid-19 pandemic. This process is known as bioactive filtration.

[0030] The polymer may be an ablative or sacrificial polymer that will wear away at the surface over time or degrade in a bulk manner, thus exposing new material to the environment. The polymer may also be a material that is incompatible with the pathogen inactivating agent such that the pathogen inactivating agent, a biocide, will ooze out of the polymer for a long period of time and thus inactivate a pathogen, such as viral particles, when they impinge on an air filter.

[0031] An ablative or sacrificial polymer may also be known as a sacrificial material with the polymer subject to wear from environmental conditions. The ablation of a polymeric matrix may occur from thermal interaction, UV interaction, and other energetic, oxidating, or hydrogenating environmental interactions. The ablative or sacrificial polymer may also be comprised of nano composites. The sacrificial polymer may wear away and break down from environmental interactions.

[0032] The polymeric material, blended with a biocide, or any pathogen inactivating material, may be applied to the substrate by various means such as spraying, dipping, roll coating, and printing. Once the polymer is applied to the substrate, it may be cured or dried through various processes such as UV cure, drying in a heated oven, or air dried.

[0033] A special class of polymers known as morphologically active polymers (MAPs) may be utilized to inactivate pathogens. The MAP may inactivate pathogens by the morphology, conformation, and / or configuration of the MAP. Page 5 of 12 ACTIVE / 124931401.1 Atty Dkt No.: IPAC-011WO

[0034] The morphologically active polymers may be thought of as a micro Venus fly trap where the pathogens are bound or trapped by the morphologically active polymer which then acts upon the pathogen to inactivate the pathogen through either morphological changes, conformational changes, configuration changes, and / or chemical deactivation.

[0035] Ionomers may be utilized as morphologically active polymers. Changes in the conformation of the ionomer due to the neutralization of the acid moieties allow for metal ion interaction with the polymer’s surrounding environment.

[0036] Through the use of the proper neutralizing moiety for an ionomer, pathogen inactivation may be incorporated into the final product. For instance, the addition of sodium hydroxide, NaOH, to an ethylene acrylic acid copolymer produces a reaction, typically in a twin screw extruder, whereby a sodium neutralized ethylene acrylic acid copolymer and H2O results from a condensation reaction. In a similar fashion, zinc acetate may be reacted with a polyethylene methacrylic acid copolymer to produce a zinc neutralized polyethylene methacrylic acid salt and acetic acid. Here, the availability of the zinc ion allows the polymer to have antimicrobial and pathogen inactivating characteristics.

[0037] In another example of the embodiment, silver acetate may be melt blended with ethylene acrylic acid or ethylene methacrylic acid. The subsequent neutralization of the acidic domain by the silver acetate results in a silver modified ionomer and acetic acid. Here, the silver ionomer has inherent antimicrobial capabilities. The silver ionomer may be partially or fully neutralized with silver acetate. In the case of full neutralization, a fatty acid may be added as a plasticizer concurrent with the neutralization process. The resulting plasticized fully neutralized ionomer may be subsequently made into a film or fiber configuration. Similar antimicrobial effects may also be obtained by substituting copper acetate for silver acetate. Here again acetic acid is liberated as the copper (II) binds to the available oxygen on the acid group of the polymer.

[0038] The stereo chemistry or conformation of various materials demonstrate different characteristics. Chiral molecules are molecules that are mirror image stereoisomers. Also known as enantiomers, chiral molecules are non-superimposable Page 6 of 12 ACTIVE / 124931401.1 Atty Dkt No.: IPAC-011WO images of each other. As an example, the stereo enantiomers of carvone, a member of the terpenoid family, have different characteristics even though the molecules are exact mirror images of each other. R-(-)-carvone has the aroma characteristics of spearmint while S-(+)-carvone has the aroma of caraway seeds. The R and S is nomenclature used by the Cahn-Ingold-Prelog Rules system. The (-) and (+) nomenclature refers to the older naming convention with (-) referring to laevo (levo) or levorotary, the ability of a chiral molecule to rotate polarized light to the left, and (+) referring to dextro or dextrorotary, the ability of a chiral molecule to rotate polarized light to the right. See Figure 1.

[0039] Here, the morphologically active polymer is configured to have a first stereochemistry conformation under one set of conditions and a different stereochemistry conformation under another set of conditions. One example of a different set of conditions is the binding of a chemical compound to the morphologically active polymer that causes the morphologically active polymer to change in the conformation. Vegetables of the Brassica oleracea group, such as broccoli, cauliflower, and cabbage, play an important role for glucosinolate consumption in the human diet and contain nitriles. However, hydrogen cyanide, also nitrile, is a deadly poison of similar chemistry.

[0040] A further example of the embodiment is a morphological structure of the polymer configured to exfoliate and expose a pathogen inactivating material that is a component of the polymer. Such exposure of the pathogen inactivating component upon exfoliation of the polymer may be brought about through an external stimulus that produces a change in the polymer conformation / morphology. Polystyrene sulfonates are utilized to treat high blood potassium, calcium, and sodium levels. However, polystyrene sulfonates can also bind to various drugs within the human digestive track and lower their absorption and effectiveness. Polystyrene sulfonates are also utilized as cation exchange resins, absorbing calcium in the place of sodium. However, as sodium is a mono cation and calcium is a dual cation, a different morphological structure results upon the transition from sodium modified molecules to calcium modified molecules.

[0041] Heparin is a relatively large polysaccharide of average molecular weight ~12,000 (corresponding to 20 disaccharide units) and having a polydispersity of ~ 1.2 Page 7 of 12 ACTIVE / 124931401.1 Atty Dkt No.: IPAC-011WO – 1.4 and a molecular weight range of 5,000 to 40,000. The heparin polymer is hydrophilic holding ~ 2-10% water even after extensive drying and is a polyelectrolyte having an average net charge of −75 / chain. This charge is maintained through a wide range of pH values as the pKa of its anionic groups are ~3.3 (carboxyl) and ~ 1.0-1.5 (O-sulfo and N-sulfo). While metallic (i.e., sodium, potassium, etc.) salts are infinitely soluble in water, and insoluble in virtually all organic solvents, quarternary alkyl (aryl) ammonium salts are extremely hydrophobic and water insoluble but are soluble in organic solvents. Heparin sodium salt in water exists as an extended helix. The length of a heparin dodecasaccharide is 5 nm, suggesting that heparin is ~9 nm in length.

[0042] Heparin has a number of chemically reactive functional groups. Each disaccharide repeating unit contains a carboxyl group. All repeating units contain one or more 1° or 2° hydroxyl groups and an average of 2-2.5 sulfo groups. N-sulfo groups are found in 75-85% of all repeating units. Approximately 15-25% of these repeating units contain a vicinal diol. Each chain contains a reducing end hemiacetal, which is a masked aldehyde group. Heparin contains ~0.3 unsubstituted amino groups / chain. These functional groups are capable of either directly attaching to a supporting matrix or accepting the introduction of a linker or spacer for attachment to a matrix.

[0043] Heparin is an excellent substitute for the ACE2 receptor that is found in the human respiratory tract. The ACE2 receptor is a receptor for pathogens, such as the spike proteins of the SARS-CoV-2 virus that is the cause of the Covid-19 pandemic.

[0044] In one example of a morphologically active polymer, heparin may be immobilized onto the surface of a cellulosic polymer such as hydroxy ethyl cellulose. The immobilization of heparin onto the cellulosic polymer allows the heparin molecule to act as an ACE2 receptor and bind highly glycosylated molecules. The spike protein on the SARS-CoV-2 virus is a highly glycosylated protein which will bind to the heparin molecule.

[0045] An example of a MAP and the interaction with the pathogen is shown by the interaction of the highly glycosylated S-1 portion of the spike protein of the SARS-CoV- 2 virus and the angiotensin-converting enzyme 2 (ACE2) synthetic receptor, or a simulated receptor, such as heparin, that is bound to a larger polymer chain, such as a polysaccharide or a polyamide. The highly glycosylated S – 1 portion of the spike Page 8 of 12 ACTIVE / 124931401.1 Atty Dkt No.: IPAC-011WO protein of the SARS-CoV-2 virus anchors the virus to the MAP so that it may be further inactivated through either other components of the MAP or companion components of a MAP / pathogen inactivating system. An example of companion components of the MAP include quaternary ammonium salts, such as benzalkonium chloride, that are chemically bound to part of the MAP polymer.

[0046] Hydrogels may also be utilized as part of the MAP system. Examples of hydrogels include poly glycolic acid, gelatin, polyvinyl alcohols of various molecular weights, guar gum, chitosan, acrylic acid gels and other similar materials. The hydrogels trap the pathogen’s as they pass through an area of a filter and inactivate the pathogenic materials by morphological changes, conformational changes, configuration changes, and / or chemical means.

[0047] The morphologically active polymer may also be incorporated into, by melt blending or other polymer processing methods, or onto, as a coating, a perforated polymer film with a perforated polymer film becomes the base material for an air filtration device. The air filtration device utilizing the perforated polymeric film may have a single layer or multiple layers. In the case of multiple layers, the perforations of the different layers are offset so as to provide a tortuous path for the air to flow through the air filter. The perforations of the polymeric film may be large or may be quite small or a mixture of both. A minimum hole size of 125 to 175 Micron / Max 1500 Micron is typical for hot needle perforation while laser perforation may be 100 µm or less.

[0048] Where there are multiple layers of film, a standoff may be utilized between the layers to separate the polymeric film layers and allow airflow through each of the polymeric foam layers.

[0049] While various aspects and embodiments have been disclosed herein, other aspects and embodiments will be apparent to those skilled in the art. The various aspects and embodiments disclosed herein are for purposes of illustration and are not intended to be limiting, with the true scope and spirit being indicated by the following claims. Page 9 of 12 ACTIVE / 124931401.1

Claims

Atty Dkt No.: IPAC-011WO What is claimed is:

1. A morphologically active polymer comprising: a morphological active structure configured to respond to a stimuli, wherein the morphology of the morphologically active polymer changes as a result of the stimuli.

2. The morphologically active polymer of claim 1, wherein the stimuli is a pathogen.

3. The morphologically active polymer in claim 1, wherein the morphologically active polymer is an ionomer comprised of an olefinic moiety, an acid moiety, and at least one cation.

4. The morphologically active polymer in claim 3, wherein the olefinic moiety is polyethylene.

5. The morphologically active polymer in claim 3, wherein the acid moiety is acrylic acid.

6. The morphologically active polymer in claim 3, wherein the acid moiety is methacrylic acid.

7. The morphologically active polymer in claim 3, wherein the cation is selected from the group consisting of lithium, sodium, potassium, magnesium, calcium, chromium, manganese, cobalt, nickel, copper, zinc, aluminum, silver, gold, and lead.

8. The morphologically active polymer of claim 1, wherein the binding site simulates an ACE2 binding site.

9. The morphologically active polymer of claim 1, wherein the binding site is heparin.

10. The morphologically at the polymer of claim 1, wherein the binding site is heparan sulfate.

11. The morphologically active polymer of claim 1, wherein the polymer backbone is a polysaccharide.

12. The morphologically active polymer (MAP) in claim 1, wherein the MAP changes at least its morphology, its conformation, or its configuration in response to a pathogen and inactivates the pathogen.

13. A morphologically active polymer comprising: a morphological structure configured to exfoliate upon exposure to an outside stimulus and; Page 10 of 12 ACTIVE / 124931401.1Atty Dkt No.: IPAC-011WO where the morphologically active polymer inactivates pathogenic organisms including fungi, viruses, bacteria, protozoa, and worms.

14. The morphologically active polymer of claim 13, wherein the outside stimulus is a glycosylated protein.

15. The morphologically active polymer of claim 13, wherein the polymer is a hydrogel.

16. The morphologically active polymer of claim 13, wherein the exfoliation process exposes a pathogen inactivating material.

17. The morphologically active polymer of claim 13, wherein the polymer is ablative or sacrificial.

18. The morphologically polymer of claim 15 where the pathogen inactivating material is a halogen moiety.

19. An air filtration device comprising: at least one layer of a perforated polymeric film and; where the perforated polymeric film is configured to inactivate pathogens.

20. The air filtration device of claim 18 where the air filtration device is comprised of multiple layers of perforated polymeric film.

21. The air filtration device of claim 19 where the multiple layers of perforated polymeric film are configured so that the perforations are offset from layer to layer.

22. The air filtration device of claim 19 where the polymeric film is configured to have a pathogen inactivating material copolymerized with the base polymer of the polymeric film.

23. The air filtration device of claim 19 where the polymeric film is coated with a pathogen inactivating material.

24. The air filtration device of claim 19 where the multiple layers of perforated polymeric film are physically separated from each other by a standoff or scaffold system.

25. The air filtration device of claim 19, wherein the perforated polymer film includes a morphologically active polymer. Page 11 of 12 ACTIVE / 124931401.1

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