EP-4734973-A2 - DISINFECTANTS WITH IODINE AND COPPER COMPLEXES FOR BIOFILM ERADICATION AND PREVENTION

Abstract

Stable antimicrobial compositions for disinfection are disclosed. Such disinfectant compositions are highly effective in reducing, preventing and/or eradicating biofilm formation and other prevalent pathogens, have extended antimicrobial and antiviral activity for more than 24 hours, have a bio-compatible pH, are suitable for personal, clinical and surgical use and are safe to skin, mucous membranes and wounds, remain stable without precipitation, discoloration or loss of antimicrobial efficacy for at least 12 months, and are beneficial for a range of applications and uses in improving and supporting human and animal health.

Inventors

• MORGAN, DOUGLAS J.
• HARRISON, STEVE
• RHODES, TANYA

Assignees

• Clyra Medical Technologies, Inc.

Dates

Publication Date

20260506

Application Date

20240625

Claims (1)

1. CLAIMS: 1. A method for reducing, preventing and/or eradicating biofilm growth comprising providing a stable liquid antimicrobial disinfectant composition comprising: a. at least 95.0% of total weight of a carrier liquid; b. potassium iodide at a first effective concentration by weight; c. copper sulfate at a second effective concentration by weight; d. wherein a mixture of the first concentration of potassium iodide and the second concentration of copper sulfate generates an amount of free iodine in the composition of from about 100 ppm to about 330 ppm; e. wherein the carrier liquid does not include any metallo-peptides, acidifying agents, buffers or surfactants; and f. wherein the composition maintains a pH of from about 4.0 to about 7.0 without discoloration or solid iodine precipitation for at least 6 months; to a surface. 2. The method of claim 1, where the composition includes from about 98% to about 99.9% by weight of the carrier liquid. 3. The method of claim 1 or 2, wherein the carrier liquid comprises purified water. 4. The method of any one of claims 1-3, wherein the carrier liquid comprises water plus NaCl at a concentration of from about 0% to about 3%. 5. The method of any one of claims 1-4, wherein the carrier liquid comprises water plus NaCl at a concentration of about 0.9%. 6. The method of any one of claims 1-5, where the copper sulfate is anhydrous copper sulfate or copper sulfate pentahydrate. 7. The method of any one of claims 1-6, wherein the first effective concentration is from about 0.025% to about 0.100% by weight, and either the copper sulfate is anhydrous copper sulfate and the second effective concentration is from about 0.016% to about 0.064% by weight, or the copper sulfate is copper sulfate pentahydrate and the second effective concentration is from about 0.025% to about 0.100% by weight. 8. The method of any one of claims 1-7, wherein the ratio of the first effective concentration to the second effective concentration is such that the ratio of the moles of potassium iodide to the moles of copper sulfate is from about 1.25 to about 1.75. 9. The method of any one of claims 1-8, wherein the first concentration is about 0.0625% by weight, and either the copper sulfate is anhydrous copper sulfate and the second effective concentration is about 0.040% by weight, or the copper sulfate is copper sulfate pentahydrate and the second effective concentration is about 0.0625% by weight. 10. The method of any one of claims 1-9, wherein an amount of free iodine generated in the composition is from about 200 to about 300 ppm. 11. The method of any one of claims 1-10, wherein an amount of free iodine generated in the composition is about 250 ppm. 12. The method of any one of claims 1-11, wherein the composition has an effective antimicrobial activity of at least three days. 13. The method of any one of claims 1-12, wherein the composition has a pH of from about 4.5 to about 6.0. 14. The method of any one of claims 1-13, wherein the composition remains stable without significant precipitation, discoloration or loss of antimicrobial efficacy for at least 24 months. 15. The method of any one of claims 1-14, wherein the biofilm is eliminated within 24 hours following providing the composition to the surface. 16. The method of any one of claims 1-15, wherein the biofilm is reduced within the first 30 minutes following providing the composition to the surface. 17. The method of any one of claims 1-16, wherein no biofilm is observed from at least 24 hours following providing the composition to the surface to at least 48 hours following providing the composition to the surface. 18. The method of any one of claims 1-17, wherein no biofilm is observed from at least 24 hours following providing the composition to the surface to at least 72 hours following providing the composition to the surface. 19. The method of any one of claims 1-18, wherein the surface is silicone. 20. The method of any one of claims 1-18, wherein the surface is titanium. 21. The method of any one of claims 1-18, wherein the surface is titanium alloy. 22. The method of any one of claims 1-21, wherein the composition is provided via lavage. 23. The method of any one of claims 1-22, wherein the composition is provided via pulsed lavage. 24. The method of any one of claims 1-22, wherein the composition is provided via static lavage. 25. The method of any one of claims 1-24, wherein the biofilm comprises microorganisms from the genus Staphylococcus.

Description

DISINFECTANTS WITH IODINE AND COPPER COMPLEXES FOR BIOFILM ERADICATION AND PREVENTION CROSS-REFERENCE TO RELATED APPLICATION [0001] The present application claims priority to U.S. Application No.18/345,895, filed on June 30, 2023, which is incorporated by reference herein in its entirety. BACKGROUND [0002] Iodine is a well-established antiseptic and has been in use for more than 150 years. It is one of the most widely accepted antimicrobials in the world as it is active against bacteria, fungi and viruses and has no known acquired resistance. [0003] The mechanisms of action for iodine can include: (1) penetration into the cell wall of the microorganism, causing blocking of the hydrogen bond which results in damage to the phospholipid cell membrane; or (2) damage to and denaturing of the proteins, nucleotides and fatty acids, leading to rapid cell death by binding to thiol and sulphydryl groups. [0004] One of the first antiseptic preparations of iodine was Lugol's solution. Developed in 1829, it consisted of an aqueous solution of elemental iodine (5%) and potassium iodide (10%) in distilled water or ethanol and was used as an antiseptic to treat wounds among other applications. However, the high levels of iodine caused pain and irritation when applied to open wounds as well as major problems and concerns regarding cytotoxicity, systemic absorption, and delayed wound healing. [0005] In 1956 povidone iodine (PVP-I) was developed, consisting of a water-soluble combination of molecular iodine and polyvinylpyrrolidone. The 10% solution generally contains 90 percent water, 8.5 percent polyvinylpyrrolidone and 1 percent iodine/iodide. The terms iodine and iodide are often used interchangeably in the literature, despite the fact that there are several different forms and complexes of iodine which may have differing properties. Povidone-iodine as used in practice to disinfect surgical sites is typically as a solution containing 10% povidone-iodine, equivalent to 1% available iodine/iodide or 10,000 ppm. The available free iodine (I2) depends on the formulation and concentration as it is a dependent equilibrium of povidone-bound iodine to free iodine. Studies have shown that most of the iodine in PVP-I is complexed in association with polyvinylpyrrolidone and iodide, with a small amount of free iodine (I2) released. [0006] The free iodine level is dependent on the concentration of the solution and follows a bell-shaped curve, with levels of 1 ppm in 10% and .001% solutions and approximately 20 ppm in .1% solutions. [0007] PVP-I, sold under the tradename Betadine®, is currently available as an antiseptic to treat minor cuts, scrapes or burns. It can be used surgically as a pre-scrub on intact skin. Betadine® is typically a 10% solution and has 1% (10,000 ppm) available iodine, but is not allowed for use in open wounds or non-intact skin. In vitro studies have suggested that PVP-I has a cytotoxic effect and can interfere with healing. Dilution may help reduce PVP-I's inhibition of the granulation and epithelialization processes involved in wound healing, but toxicity concerns remain. As a result, any off-label use of this product on non-intact skin, in wounds, or on or in surgical sites generally involves a very short application time followed by an immediate flush with saline. Effects of this dilution followed by saline flushing have not been comprehensively tested or proven with respect to the resulting cytotoxicity or antimicrobial profile and such a use is carried out without any recognized approvals for that indication. [0008] Persistent use of antibiotics (antibacterials) has provoked the emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) bacteria, which render even the most effective drugs ineffectual. One of the advantages of iodine as an antimicrobial is that bacterial resistance does not develop even with extended use as it does for many antibiotics. Hospital acquired infections are a serious and persistent problem, in part because many such pathogens have developed or exhibit multidrug resistance and virulence. Six of the most common and noxious nosocomial (hospital acquired) pathogens are known by the acronym ESKAPE, which includes: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter. [0009] Viruses are another form of pathogen addressed with antimicrobials. [0010] Coronaviruses are positive-stranded RNA viruses with large genome sizes that are known to cause diseases in animals and in humans. In humans, coronaviruses can cause respiratory tract infections that may be mild, such as the common cold. [0011] But coronaviruses can also cause much more serious infections such coronavirus- induced severe acute respiratory syndrome (SARS). Woo et al., Microbiol. Immunol. 49:899-908 (2005). Seven strains of human coronaviruses are known: human coronavirus 229E (HCoV-229E); human coronavirus OC43 (HCoV-OC