copper as a med treatment

Joint Accessions Research and Best Practices Symposium – April 18, 2007

Innovative Technology For Medicine

COPPER

Richard C. Zatcoff, D.P.M. DABPS, FACFAS, FACFAOM

Historic PerspectiveHistoric Perspective

• The ancient Greeks (400 BC) discover the sanitizing power of copper. They prescribed copper for pulmonary diseases and for purifying drinking water.

• Copper strips were nailed to ships’ hulls by the early Phoenicians to inhibit fouling.

• American Pioneers put silver and copper coins in large wooden water casks to assure safe drinking water.

• In World War II, Japanese soldiers put pieces of copper in their water bottles to help prevent dysentery.

• NASA uses copper for water purification

Resistance to copperResistance to copperWhile copper has been used for thousands of

years, as opposed to antibiotics, no micro-organism has evolved which is resistant to

constant exposure to copper.

Although some organisms have reduced sensitivity to excess copper, as a rule, exposure of micro-organisms to high concentrations of

copper results in damage to cellular components.

Copper

Benefits in Human Health

Essential Metals for Human Health

Copper Calcium

Cobalt Chromium

Iron Potassium

Magnesium Manganese

Sodium Nickel

Zinc

The adult body contains between 1.4 – 2.1 mg of copper per kilogram of body weight.

•Highest concentration of copper found in brain and liver

•Approx. 50% of total copper content of the body is found in the bones and muscles

AbsorptionAbsorption

•Newly absorbed copper is transported to body tissues by plasma protein carriers especially ceruloplasmin

•Copper combines with certain proteins to produce enzymes.

Linder, Wooten, et. al., AM. J. CLIN. NOTR. 67.1998Levenson, AM. J. CLIN. NOTR. 67.1998

Additional Properties of CopperAdditional Properties of Copper

• Anti-bacterial

• Anti-fungal

• Anti-viral

Today soluble copper is used as a: Water Purifier

Algicide Fungicide

Molluscicide Bactericide

Question: Can non-soluble copper have biocidal

properties?

Answer: Yes! Non-soluble copper has potent biocidal

properties!

How the biocidal effect is achieved?

Cell membrane permeability and lipid peroxidation. Displacement of essential metals from their native binding

sites. Interference with oxidative phosphorylation and osmotic

balance. Alterations in the conformational structure of nucleic acids

and proteins. Redox cycling between Cu+2+2 and Cu+1 catalyzes the

production of highly hydroxyl radicals, with subsequent damage to biomolecules, such as lipids, proteins, DNA and RNA.

Borkow G, et al. Current Medicinal Chemistry. 2005;12:2163-2175

Water bridge

Copper molecule

ion release

The Simple Chemistry

Copper ions

Damage bacterial cell wall

Copper Oxide

Damage bacterial DNA

Damage bacterial proteinsBacteria/fungi

No Development of Resistant Microbes!!

• Bacteria require Cu+1 and Cu+2+2 to survive

• CsoR – protein that allows the causative agent of bacteria including TB and S. aureus to respond to Cu

Giedroc D, Chem and Eng News, Dec 11, 2006, Vol 84: #50, pg 12

Cu+1 or Cu+2+2

CsoR- Settles backon bacterial DNA

blocking further genetranscription

CsoRBacterial DNA

CsoR Cu+1or Cu+2+2

Bacterial transcription - genes, leading to a protein pump that kicks out copper

DecreasedCu

Possible Primary Cu Sensing Protein in Majority of Bacteria

Giedroc D, Chem and Eng News, Dec 11, 2006, Vol 84: #50, pg 12

Requirement for Cu in angiogenesis

Ziche M, et al. J. Natl Cancer Inst. 1982 Aug; 69(2):475-482

Harris E.D., Nutr Rev 2004 Feb; 62(2):60-4

Wound HealingWound Healing

• Copper helps to form cross-links in collagen and elastin.

• Helps promote, maintain, and repair connective tissues.

• Active during proliferation and remodeling phases.

Diegelmann, Evans, Front. BIOSCI. 2004

Cupron Copper Gauze PadCupron Copper Gauze Pad

10cm x 10cm10cm x 10cm

3% Cupron3% Cupron

Gamma IrradiatedGamma Irradiated

Copper Impregnated Gauze Pads by Cupron, Inc.

Start treatment 2 Weeks of treatment

4 Weeks of treatment 10 Weeks of treatment

71 YO WM Diabetic

4 Months of treatment

Start treatment 2 Weeks of treatment

55 YO WF Diabetic

9 Months of Treatment

1-30-2007

5 Months of treatment

2 Weeks of treatmentStart treatment

75 YO WM Diabetic,PVD

#160 04-03-06

3 months before treatment2 months of treatment

12 months of treatment

81 YO WM Diabetic, PVD

Biocidal, not just biostatic

Broad spectrum:

Destroy Gram+ and Gram- bacteria

Destroy fungi

Destroy viruses

Last for the life of the fabric

Be durable:

Withstand chemical exposure

Withstand hot water exposure

It must be safe for human use

Qualities that an anti-microbial fabric should have

Plating of Cellulose with Copper Oxide Compounds

a

X 2,000

b

Cellulose Fiber

c

X 2,000

d

Copper-Coated Fiber

X 2,000

e f

Washed Copper-Coated Fiber

X 200

X 1,500

Inclusion of Copper Oxide into Polymeric Materials

• Polyester,

• Polypropylene,

• Polyurethane,

• Polyolefin,

• Polyethylene, and

• Nylon fabrics

In Vitro StudiesIn Vitro Studieswith Copper Treated with Copper Treated Fibers/FabricsFibers/Fabrics

Staphylococcus aureus

CFU per sample

103 104 105 106

120 min0 min

Production Fabrics

Printed Cupron Fabric

Control Fabric (no copper)

Dyed Cupron Fabric

Anti-bacterial Activity

Subcontract laboratory performing tests: AminoLab Laboratory Services, Weizman Industrial Park, Nes Ziona 79400, Israel

Gram+

Escherichia coli

CFU per sample

103 104 105 106

120 min0 min

Production Fabrics

Printed Cupron Fabric

Dyed Cupron Fabric

Control Fabric (no copper)

Subcontract laboratory performing tests: AminoLab Laboratory Services, Weizman Industrial Park, Nes Ziona 79400, Israel

Gram-

Subcontract laboratory performing tests: Hy Laboratories Ltd., Park Tamar, Rehovot 76325, Israel

Drug Resistant Bacteria

Candida albicans

minutes

0 10 20 30 40 50 60

nu

mb

er

of

fun

gi

0

10000

20000

30000

40000

50000

60000

Anti-fungal Activity

Subcontract laboratory performing tests: AminoLab Laboratory Services, Weizman Industrial Park, Nes Ziona 79400, Israel

e.g. Inactivation of Viruses:• Bronchitis Vaccine Virus - Jordan & Nassar (1971)

Vet. Rec. 89:609-10. • Herpesvirus types 1 and 2 - Coleman et al (1973)

Antimicrob. Agents Chemother 4:259-62.• Poliovirus - Totsuka & Ohtaki (1974)

Jpn. J. Microbiol18:107-12.• Bacteriophages - Yamamoto et al (2001)

Biochem. Biophys. Acta. 91:257.• HIV-1 – Sagripanti & Lightfoote MM (1996)

AIDS Res. Hum. Retroviruses 12:333-7.• Enteroviruses, Rotaviruses, etc.

Copper Biocidal Activity Copper Biocidal Activity Is Very Well Documented Is Very Well Documented

Antiviral potency of Cupron Filters

Virus Infectivity Reduction

HIV-1 >99.99%Punta Toro >99.99%

Rhinovirus 2 99.99%

Pichinde 99.99%

CMV 99.95%

Measles 99.95%

Influenza A 99.5%

WNV 99.5%

RSV 99%

Parainfluenza 3 96%

Yellow Fever 95%

VEE 94%

Vaccinia 80%

HIV-1 - Dr. Borkow at the Kaplan Medical Center;

CMV - Dr. Yonat Shemer, Ben Gurion University;

WNV – Harlan Laboratories;Other viruses - Dr. Robert W.

Sidwell, Director of The Institute for

Antiviral Research, Utah State University, Utah, under a

subcontract from the NIH.

Percent of reduction of the infectivity of viruses following their passage through Cupron filters

Animal StudiesAnimal Studies

Guinea Pig Maximization Test (ISO 10993-10 (1994) guideline). BSL Bioservice Scientific Laboratories GmbH, Munich 80797, Germany

Rabbit Skin Irritation Test. (Biological Evaluation of Medical Devices – ISO 10993-10) Harlan Biotech Israel, Kiryat Weizmann, Rehovot

No Skin Irritation or

Allergenicity

X-Static Fiber Vs. Cupron Fiber Candida albicans

Washing Cycles

0 5 10 20 25 50 100 1 2

Co

lon

ies

Fo

rmin

g U

nit

s/sa

mp

le

0

2000

4000

6000

8000

10000

12000

14000

X-StaticCupronControl fungi

controlfungi

Colony forming units/sample

101 102 103 104 105 106

Negative Control

Cupron Fabric

Cupron Fabric after 50 washes

0 minutes

120 minutes

Escherischia coli

103 104 105 106

Negative Control

Cupron Fabric

Cupron Fabric after 50 washes

Staphylococcus aureus

Percent Reduction

99.3

99.95

99.8

99.3

Broad Spectra of Bioactivities

Antimicrobial

Antifungal

Antiviral

Gram +

Gram –

Drug Resistant Bacteria:

MRSA, VRE

RNA Viruses

DNA Viruses

Enveloped Viruses

Non-enveloped Viruses

Antimite

Candida

(Athlete’s foot)

Introduction of Copper Oxide

into

Cotton

Fibers

Copper

Fibers

Antifungal Socks

Acaricidal Mattress Covers

Antibacterial Garments

Athlete’s foot,

Diabetics

Dust miteallergies

Hospitals (NosocomialInfections)

Antiviral Gloves

Antiviral Condoms

Hospitals,Paramedics

STDs

Latex

Copper Latex

Polymer Fibers

Copper Polymer Fibers

Antiviral Filters

Antibacterial Filters

Blood Banks, Hospitals,Milk and dialysis pumps,

Airports, Planes (air filters)

Copper Sole™ Socks Copper Sole™ Socks A Revolutionary TechnologyA Revolutionary Technology

Investigation byInvestigation byRichard Zatcoff D.P.M.Richard Zatcoff D.P.M.

Upstate PodiatryUpstate PodiatrySimpsonville, SCSimpsonville, SC

September 2004 – September 2004 – January 2005January 2005

N=56N=56 Males - 40Males - 40

Females – 16Females – 16 Diabetics – 21Diabetics – 21 Ages 21 - 85Ages 21 - 85

•Clinical Observations Only•No Cultures Taken•No Topical or Oral Anti-Fungals•No Topical or Oral Steroids•Concurrent Antibiotics Two Patients

Contents78% Polyester / 12% Cupron Polyester / 9% Nylon / 1% Lycra

Contents81% Polyester / 11% Cupron Polyester / 7% Nylon / 1% Lycra

56 Patient-Clinical Study*56 Patient-Clinical Study*

Clinically TestedClinically Tested Patients were compared to historical controls.Patients were compared to historical controls. Patients with CupronPatients with Cupron®® yarn socks were observed for yarn socks were observed for

improvement or resolution in the following conditions:improvement or resolution in the following conditions:-Erythema-Erythema -Vesicular eruptions-Vesicular eruptions-Burning/itching-Burning/itching -Fissures-Fissures-Scaling-Scaling -Drainage-Drainage-Edema-Edema -Odor-Odor

*2004-2005 Study, R.C. Zatcoff, D.P.M. Upstate Podiatry, Greenville, SC

Another ObservationAnother Observation

9-9-04 10-7-04

*Dr. Zatcoff, Upstate Podiatry, Greenville, SC

The healing power of copper-ion technology first eliminates microbial growth and then commences angiogenesis.

51 YO WF Diabetic51 YO WF Diabetic

09-08 09-22

09-08 09-22

84 YO WM Diabetic

09-27 10-04

#1985 80 YO WM - #1985 80 YO WM - DiabeticDiabetic

#8045 72 YO WM#8045 72 YO WM

#9008 73 YO WM - #9008 73 YO WM - DiabeticDiabetic

#9679 58 YO WM#9679 58 YO WM

#9835 75 YO WM - #9835 75 YO WM - DiabeticDiabetic

#9871 67 YO WM#9871 67 YO WM

#8906* 49 YO BF - #8906* 49 YO BF - DiabeticDiabetic

Mitigating FactorsMitigating Factors

Participant Compliance – Wear Participant Compliance – Wear TimeTime

Possible degradation of Cupron Possible degradation of Cupron FibersFibers

Persistent infection from nail Persistent infection from nail reservoirreservoir

Co-morbidity effectsCo-morbidity effects

A. ERYTHEMA (51 patients):A. ERYTHEMA (51 patients):All 51 patients improved; 22 (42%) resolved completely over an All 51 patients improved; 22 (42%) resolved completely over an average period of 9 days (range 4-28 days).average period of 9 days (range 4-28 days). The 95% confidence The 95% confidence interval for resolution was (0.29, 0.58).interval for resolution was (0.29, 0.58).

ERYTHEMA, 9 DAY AVERAGE FOLLOW-UP

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A1. Longer term study (22 patients):A1. Longer term study (22 patients): Nineteen (86%) maintained their improvement or resolved, 95% CI Nineteen (86%) maintained their improvement or resolved, 95% CI (0.65, 0.97). Three patients (14%) did not maintain improvement or (0.65, 0.97). Three patients (14%) did not maintain improvement or reverted to “present”, 95% CI (0.03, 0.34). The average length of follow-reverted to “present”, 95% CI (0.03, 0.34). The average length of follow-up was 36 days. Diabetics and patients older than 65 shared in the up was 36 days. Diabetics and patients older than 65 shared in the improvement, both early and long-term.improvement, both early and long-term.

ERYTHEMA, AVERAGE FOLLOW-UP OF 36 DAYS

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B. SCALING (56 patients):B. SCALING (56 patients): Fifty-five (55) of the 56 improved (98%), 5 resolved (9%), and 1 stayed Fifty-five (55) of the 56 improved (98%), 5 resolved (9%), and 1 stayed the same. The 95% confidence interval for some improvement is (0.90, the same. The 95% confidence interval for some improvement is (0.90, 1.00); for resolution (0.03, 0.20). Both of the p-values are highly 1.00); for resolution (0.03, 0.20). Both of the p-values are highly significant for efficacy.significant for efficacy.

SCALING, AVERAGE TREATMENT OF 9 DAYS

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B1.B1. Longer term study (24 patients):Longer term study (24 patients):Twenty-one (88%) held improvement or resolved, 3 reverted with an Twenty-one (88%) held improvement or resolved, 3 reverted with an average follow-up of 34 days. The 95% confidence interval is (0.68, average follow-up of 34 days. The 95% confidence interval is (0.68, 0.97) with a p-value <0.001. Again, diabetics and elderly shared in the 0.97) with a p-value <0.001. Again, diabetics and elderly shared in the improvement.improvement.

SCALING, AVERAGE FOLLOW-UP 34 DAYS

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C.FISSURING (37 patients):C.FISSURING (37 patients): All 37 patients improved; 15 (40%) resolved completely with an average All 37 patients improved; 15 (40%) resolved completely with an average follow-up of 10 days, 95% CI (0.25, 0.58). This is highly significant.follow-up of 10 days, 95% CI (0.25, 0.58). This is highly significant.

FISSURING, AVERAGE FOLLOW-UP OF 10 DAYS

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C1.C1. Longer term study (17 patients):Longer term study (17 patients): All 17 patients improved, 6 (35%) resolved completely in an average All 17 patients improved, 6 (35%) resolved completely in an average follow-up of 39 days, 95% CI (0.14, 0.62). Again, diabetics and elderly follow-up of 39 days, 95% CI (0.14, 0.62). Again, diabetics and elderly shared in the improvement.shared in the improvement.

FISSURING, AVERAGE FOLLOW-UP OF 39 DAYS

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D. BURNING OR ITCHING (23 patients):D. BURNING OR ITCHING (23 patients): Nineteen of the 23 improved (83%), four stayed the same or reverted in Nineteen of the 23 improved (83%), four stayed the same or reverted in the average follow-up period of 8 days. The 95% confidence interval is the average follow-up period of 8 days. The 95% confidence interval is (0.61, 0.95) with a p-value of 0.003, again highly significant.(0.61, 0.95) with a p-value of 0.003, again highly significant.

BURNING OR ITCHING, AVERAGE FOLLOW-UP OF 8 DAYS

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D1. Longer term study (8 patients):D1. Longer term study (8 patients): All 8 patients were unchanged over an average All 8 patients were unchanged over an average follow-up of 46 days, meaning that their initial follow-up of 46 days, meaning that their initial improvement was maintained. The numbers were too improvement was maintained. The numbers were too small to study diabetics and elderly.small to study diabetics and elderly.

BURNING OR ITCHING, AVERAGE FOLLOW-UP OF 46 DAYS

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E. VESICULAR ERUPTIONS (23 patients):E. VESICULAR ERUPTIONS (23 patients):

All 23 patients improved; 13 (56%) resolved All 23 patients improved; 13 (56%) resolved completely, 95% CI (0.34, 0.76).completely, 95% CI (0.34, 0.76).

VESICULAR ERUPTIONS, AVERAGE FOLLOW-UP OF 8 DAYS

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E1. Longer term study (10 patients):E1. Longer term study (10 patients):All 10 patients maintained their improvement or All 10 patients maintained their improvement or resolved (6) over an average follow-up of 45 days. resolved (6) over an average follow-up of 45 days. The proportions were similar for both diabetics and The proportions were similar for both diabetics and patients over the age of 65.patients over the age of 65.

VESICULAR ERUPTIONS, AVERAGE FOLLOW-UP OF 45 DAYS

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CONCLUSIONCONCLUSION Compared to historical controls, patients with Cupron ® socks had Compared to historical controls, patients with Cupron ® socks had significant improvement or resolution in the following conditions:significant improvement or resolution in the following conditions:- Erythema- Erythema - Vesicular eruptions- Vesicular eruptions- Burning/itching- Burning/itching - Fissures- Fissures- Scaling- Scaling - Drainage- Drainage- Edema- Edema - Odor- Odor

Moreover, since nearly 40% (19 of 51) of the group was either Moreover, since nearly 40% (19 of 51) of the group was either diabetic or older than 65 (10 were both diabetic and older than 65), diabetic or older than 65 (10 were both diabetic and older than 65), this study is statistically significant for improvement or resolved this study is statistically significant for improvement or resolved for all the above conditions for people with diabetes, including for all the above conditions for people with diabetes, including elderly diabetics.elderly diabetics.

Statistical Review – Michael S. Smith, MD MS Statistical Review – Michael S. Smith, MD MS

Continuous Antimicrobial Product Protection  

The Widest Spectrum anti-microbial known today

Anti-odor Anti-microbial Anti-Fungal (including Athlete’s Foot,

Yeast Infections, Ring Worm) Anti-Mite Anti-Viral (including HIV, SARS, West

Nile, Hepatitis, Influenza) Promotes Healing of Sores and Wounds Fully Patent Protected Available in Polyester, Nylon,

Polypropylene, Cotton, Tencel Published in the Yale Medical Journal

A solution based product Biocidal, not just biostatic

Broad spectrum in its ability to destroy Gram+ (MRSA) and Gram-(VRE) bacteria

Broad spectrum in its ability to destroy fungi

Broad spectrum in its ability to destroy viruses

Ability to promote wound healing

Cosmetic benefits of better looking skin

Fungi Bacteria