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Putting copper into action: copper-impregnated products with potent biocidal activities

Cupron Inc., New York, New York, USA

¹Correspondence: Hameyasdim 44, Kfar Gibton 76910, Israel. E-mail: gadi{at}cupron.com

SPECIFIC AIMS

We hypothesized that introducing copper into many different types of products would provide them with biocidal qualities. Here we demonstrate the broad-spectrum anti-bacterial, anti-viral, anti-fungal, and anti-mite activities of fibers and polyester products permanently impregnated with copper and discuss the possible effect of these products on central public health concerns.

PRINCIPAL FINDINGS

1. Bactericidal, anti-fungal, and acaricidal activity of fabrics containing copper-treated fibers
The anti-bacterial effectiveness of untreated cotton fibers (referred to as control fabrics) and fabrics containing 20% (w/w) fibers impregnated with copper and 80% non-copper-treated cotton fibers (referred to as copper fabrics) on Staphylococcus aureus and Escherichia coli are shown in Fig. 1 a. Copper fabrics reduced by >2 logs the number of recoverable E. coli and S. aureus bacteria within 2 h of their being exposed to copper fabrics.

View larger version (36K): [in this window] [in a new window]   Figure 1. Anti-bacterial, anti-fungal, and acaricidal activity of copper fabrics. a) 1 ± 0.1 mL of a 24 h broth/bacteria culture were exposed to swatches of 20% copper fabrics or control fabrics for 1 min (0 h) and 2 h (E. coli and S. aureus). Methicillin-resistant stapyhloccus aureaus (MRSA) and vancomycin-resistant enterococci (VRE) were exposed for 1 min and 1 h. The bacterial titer was then determined by standard Pour Plate Count. *Copper fabrics were subjected to 35 subsequent washes at 85°C before testing. Control fabrics subjected to the same washing treatment did not affect bacteria growth (not shown). b) 1 ± 0.1 mL of a 24 h broth containing C. albicans were exposed between 0 to 60 min to swatches of control fabric (•) or 20% copper fabric (). c) Approximately 200 dust mites (D. farinae) were cultured for 48 days in the presence of swatches of control fabric (•), 20% copper fabric (), 100% copper fibers () or in the absence of any swatches (). Mortality was recorded by counting the living mites under a stereo-microscope.

Fabrics subjected to drastic washing conditions (35 industrial washings at 85°C) also reduced by >2 logs the viability of S. aureus within 2 h of bacteria exposure to the copper fabric (Fig. 1a ). Similar results were obtained with methicillin-resistant S. aureus (MRSA) and vancomycin-resistant Enterococci (VRE) bacteria (Fig. 1a ).

Copper fabric reduced the number of viable fungi (Candida albicans) in a time-dependent manner (Fig. 1b ). Complete inhibition was noted within 60 min after fungi were exposed to the fabric. In contrast, the control fabric did not affect the fungus’s viability.

Based on this result, socks, containing 10% (w/w) copper-coated fibers to uncoated fibers, were given to 50 individuals suffering from tinea pedis (athlete’s foot). All 50 individuals reported that within 2–6 days of using the socks, the blistering and fissures characteristic of this fungal infection disappeared and the skin returned to normal. None of the 50 individuals reported adverse effects after using the copper-impregnated socks.

The effect of two fabrics, one containing 20% copper fibers and one containing 100% copper fibers (w/w), were tested for acaricidal activity (Fig. 1c ). While all mites exposed to control fabrics were alive after 12 days, >60% and 100% of mites exposed to the 100% copper fabric were dead after 1 and 5 days, respectively. Approximately 50% of the mites exposed to the 20% copper fabrics died within 12 days of exposure to the fabrics. After 47 days of culture, 86% and 67% of the mites in the absence of any fabric and in the control fabric containers were alive whereas all mites exposed to the 20% copper fabric were dead.

2. Anti-viral activity of latex and polyester impregnated with copper
Copper ions have been reported to inactivate HIV-1. We investigated whether our copper-impregnated latex would reduce HIV-1 infectivity. Indeed, HIV-1 infectivity was reduced in a dose-dependent manner when HIV-1 was exposed to latex gloves containing increasing concentrations of copper (Fig. 2 a).

View larger version (18K): [in this window] [in a new window]   Figure 2. Anti-viral activity of copper-impregnated latex and copper-impregnated polyester. a) 50 µL drops containing HIV-1IIIB were placed on top of latex gloves impregnated with different amounts of copper. After 20 min of incubation at room temperature, the drops were mixed with MT-2 cells. HIV-1IIIB-exposed cells were incubated for 4 days at 37°C, then reverse transcriptase activity in the supernatant was determined. b) Saquinavir-resistant HIV-1 in medium (10 mL) was passed through syringes containing 4 mL of polyester (dark symbols) or copper-polyester fibers (light symbols: each line/symbol represents a different examined filter). The reduction of infectivity of the filtered virus was determined as follows: immediately after filtration, sequential 10-fold dilutions of the filtrate were done in RPMI medium in 6 rows of wells in a 96-well plate. Subsequently, MT-2 target cells in medium containing 10% FCS prepositioned in 6 separate wells in a 96-well plate were exposed to each dilution of the virus; for each viral dilution 6 replicate wells were used. After 6 days of culture at 37°C, viral infectivity was determined by microscopic assessment. MT-2 infection by T-tropic HIV-1 isolates results in syncytia formation. Each well where even one syncytia was observed was considered a positive well, i.e., infected with HIV-1. Results represent the number of positive wells infected with HIV-1 for each viral dilution. c) WNV was filtered and diluted as in panel b. All viral dilutions were added to precultured Vero cells; 6 replicate wells were used for each viral dilution. After 6 days of culture at 37°C, the cytopathic effects caused by the virus were monitored. Each well in which cytopathic effects were observed was considered a positive well (i.e., an infected well). Results represent the number of positive wells infected with WNV for each viral dilution.

HIV-1 is transmitted through body fluids (e.g., blood and mother’s milk). Accordingly, syringes filled with polyester fibers impregnated with copper were prepared to serve as "filters." As depicted for a representative experiment in Fig. 2b , filtration of medium containing Saquinavir-resistant HIV-1 through syringes containing copper polyester fibers resulted in >5 log reduction of the viral infectious titers. The filters deactivated all the T-tropic and M-tropic isolates, laboratory and clinical isolates, and nucleoside, non-nucleoside, and protease-resistant viral isolates tested. Similar results were obtained when West Nile virus (WNV) was filtered (Fig. 2c ).

3. Test for skin sensitization
To determine whether extracts of the copper-impregnated fabrics have skin sensitizing properties, a Guinea Pig Maximization Test and a Rabbit Skin Irritation Test were conducted. None of the 10 guinea pigs or 3 rabbits exposed to extracts of copper fabrics showed allergic skin reactions or skin irritation as compared with intraspecific application of the extraction vehicle and when compared with the animals of the control group. None of the animals exhibited any other toxic effects or clinical signs resulting from the treatment with the extracts of the copper-impregnated fabrics.

CONCLUSIONS AND SIGNIFICANCE

An inexpensive platform technology was developed that binds copper to textile fibers from which woven and unwoven fabrics can be produced. Copper may be integrated into latex and other polymeric products during manufacture. As demonstrated here, these copper-impregnated products possess broad-spectrum anti-microbial properties. This technology, for example, enables production of anti-viral gloves and filters (which inter alia deactivate HIV-1 and other viruses), anti-bacterial self-sterilizing fabrics (which kill antibiotic-resistant bacteria, including MRSA and VRE), anti-fungal socks (which alleviate symptoms of athlete’s foot), and anti-dust mite mattress-covers (which reduce mite-related allergies).

Copper is considered safe to humans, as demonstrated by the widespread and prolonged use by women of copper intrauterine devices (IUDs). Very low risk of adverse skin reactions is associated with copper. Animal testing described above has demonstrated that copper fabrics do not possess skin-sensitizing properties. None of the 50 individuals who used socks containing copper-impregnated fibers reported any negative effects caused by the socks.

In contrast to the low sensitivity of human tissue to copper, microorganisms are extremely susceptible to copper. Toxicity occurs through the displacement of essential metals from their native binding sites, from interference with oxidative phosphorylation and osmotic balance, and from alterations in the conformational structure of nucleic acids, membranes and proteins.

Introducing copper into fabrics, latex, or other polymers may have significant ramifications. One example is the reduction of nosocomial infections in hospitals. Healthcare-associated (nosocomial) infection ranks fourth among causes of death in the U.S., behind heart disease, cancer, and stroke. It has been demonstrated that sheets in direct contact with a patient’s skin and his bacterial flora are an important source of infection. Therefore, use of self-sterilizing pajamas, sheets, pillow covers, and robes in a hospital setting may reduce nosocomial infections. Use of gloves with anti-bacterial and anti-viral properties by hospital personnel may also aid in reducing transmission of infectious microbes and viruses and provide increased protection to hospital personnel.

Another possible use of copper fabrics is related to allergies and asthma. It is estimated that 15% of the general population suffer from allergic disorders, of which allergic rhinitis is the most common. Dust mites are an important source of allergen for perennial rhinitis and asthmatic attacks. Thus, elimination of house dust mites in mattresses, quilts, carpets, and pillows would improve the quality of life of those suffering from dust mite-related allergies.

Another potential use of copper-impregnated fabrics is related to foot ulcerations, a common complication of type 2 diabetes that afflicts 130 million individuals worldwide. In many cases these ulcerations can become severe due to cuts/bruises that heal slowly and become infected. An infection that does not heal can cause the tissue to die (gangrene). Use of socks containing copper-impregnated fibers by diabetics may significantly reduce the risk of foot infection.

Use of copper-impregnated socks by the wider population may be beneficial in more benign conditions. About 15–20% of the population suffers from tinea pedis. This fungal infection can cause discomfort, may be resistant to treatment, and may spread to other parts of the body or to other people. We found that copper-impregnated socks may be useful in preventing and treating tinea pedis.

An important potential application of copper-impregnated materials is the reduction of bacterial and viral transmission during transfusion of blood or blood-related products. A growing number of viral, bacterial, and protozoa pathogens have been identified in blood products, and new pathogens are regularly identified as being present. In parts of the world where screening tests are too expensive to be performed regularly, a cheap, rapid virus inactivation filter would be extremely helpful. Accordingly, a filter that can inactivate a broad spectrum of viruses in blood products would be very valuable.

Preliminary results showing neutralization of HIV-1 and WNV infectivity when viruses were passed through our copper containing syringes indicate the possibility of producing a generic anti-viral filter. However, it must first be established that these filters do not damage filtered plasma and other blood components and do not harm individuals infused with these blood products. We are currently conducting these studies.

Transmission of HIV during lactation accounts for one-third to one-half of all HIV mother-infant transmissions. Breast milk may be passed through a copper fiber-containing filter, reducing HIV infectivity. If there is no degradation of the milk’s essential nutrients, the filtered milk may be fed to infants, thereby reducing the risk of HIV transmission. Admittedly, implementing such measures may be difficult because of sociological factors existing in developing countries. However, HIV-1, as well as other viruses, will be with us for many years and methods to reduce their impact must be developed.

In conclusion, our study demonstrates potential uses of copper in new applications that address medical concerns of the greatest importance. Implementation of even a few of the possible applications of this novel technology may have a major effect on our lives.

View larger version (42K): [in this window] [in a new window]   Figure 3. Potential health-related applications of impregnating copper in cotton or polymer fibers or latex.

FOOTNOTES

To read the full text of this article, go to http://www.fasebj.org/cgi/doi/10.1096/fj.04-2029fje;

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This Article Full Text (PDF) All Versions of this Article: 18/14/1728 04-2029fjev1    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by BORKOW, G. Articles by GABBAY, J. Search for Related Content PubMed PubMed Citation Articles by BORKOW, G. Articles by GABBAY, J.