copper as a med treatment
DESCRIPTION
Copper treated fabrics can function as antibiotics and healing accelerators.TRANSCRIPT
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Joint Accessions Research and Best Practices Symposium – April 18, 2007
Innovative Technology For Medicine
COPPER
Richard C. Zatcoff, D.P.M. DABPS, FACFAS, FACFAOM
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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.
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• In World War II, Japanese soldiers put pieces of copper in their water bottles to help prevent dysentery.
• NASA uses copper for water purification
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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.
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Copper
Benefits in Human Health
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Essential Metals for Human Health
Copper Calcium
Cobalt Chromium
Iron Potassium
Magnesium Manganese
Sodium Nickel
Zinc
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The adult body contains between 1.4 – 2.1 mg of copper per kilogram of body weight.
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•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
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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
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Additional Properties of CopperAdditional Properties of Copper
• Anti-bacterial
• Anti-fungal
• Anti-viral
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Today soluble copper is used as a: Water Purifier
Algicide Fungicide
Molluscicide Bactericide
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Question: Can non-soluble copper have biocidal
properties?
Answer: Yes! Non-soluble copper has potent biocidal
properties!
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How the biocidal effect is achieved?
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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
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Water bridge
Copper molecule
ion release
The Simple Chemistry
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Copper ions
Damage bacterial cell wall
Copper Oxide
Damage bacterial DNA
Damage bacterial proteinsBacteria/fungi
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No Development of Resistant Microbes!!
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• 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
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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
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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
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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
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Cupron Copper Gauze PadCupron Copper Gauze Pad
10cm x 10cm10cm x 10cm
3% Cupron3% Cupron
Gamma IrradiatedGamma Irradiated
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Copper Impregnated Gauze Pads by Cupron, Inc.
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Start treatment 2 Weeks of treatment
4 Weeks of treatment 10 Weeks of treatment
71 YO WM Diabetic
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4 Months of treatment
Start treatment 2 Weeks of treatment
55 YO WF Diabetic
9 Months of Treatment
1-30-2007
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5 Months of treatment
2 Weeks of treatmentStart treatment
75 YO WM Diabetic,PVD
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#160 04-03-06
3 months before treatment2 months of treatment
12 months of treatment
81 YO WM Diabetic, PVD
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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
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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
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X 200
X 1,500
Inclusion of Copper Oxide into Polymeric Materials
• Polyester,
• Polypropylene,
• Polyurethane,
• Polyolefin,
• Polyethylene, and
• Nylon fabrics
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In Vitro StudiesIn Vitro Studieswith Copper Treated with Copper Treated Fibers/FabricsFibers/Fabrics
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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+
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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-
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Subcontract laboratory performing tests: Hy Laboratories Ltd., Park Tamar, Rehovot 76325, Israel
Drug Resistant Bacteria
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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
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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
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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
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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
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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
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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
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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)
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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)
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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
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September 2004 – September 2004 – January 2005January 2005
N=56N=56 Males - 40Males - 40
Females – 16Females – 16 Diabetics – 21Diabetics – 21 Ages 21 - 85Ages 21 - 85
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•Clinical Observations Only•No Cultures Taken•No Topical or Oral Anti-Fungals•No Topical or Oral Steroids•Concurrent Antibiotics Two Patients
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Contents78% Polyester / 12% Cupron Polyester / 9% Nylon / 1% Lycra
Contents81% Polyester / 11% Cupron Polyester / 7% Nylon / 1% Lycra
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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
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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.
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51 YO WF Diabetic51 YO WF Diabetic
09-08 09-22
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09-08 09-22
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84 YO WM Diabetic
09-27 10-04
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#1985 80 YO WM - #1985 80 YO WM - DiabeticDiabetic
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#8045 72 YO WM#8045 72 YO WM
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#9008 73 YO WM - #9008 73 YO WM - DiabeticDiabetic
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#9679 58 YO WM#9679 58 YO WM
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#9835 75 YO WM - #9835 75 YO WM - DiabeticDiabetic
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#9871 67 YO WM#9871 67 YO WM
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#8906* 49 YO BF - #8906* 49 YO BF - DiabeticDiabetic
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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
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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
0
5
10
15
20
25
30
35
SAME OR WORSE IMPROVED RESOLVED
NU
MB
ER
S O
F P
AT
IEN
TS
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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
0
5
10
15
20
25
30
35
SAME OR WORSE IMPROVED RESOLVED
NU
MB
ER
S O
F P
AT
IEN
TS
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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
0
10
20
30
40
50
60
SAME OR WORSE IMPROVED RESOLVED
NU
MB
ER
S O
F P
AT
IEN
TS
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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
0
10
20
30
40
50
60
SAME OR WORSE IMPROVED RESOLVED
NU
MB
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S O
F P
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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
0
5
10
15
20
25
SAME OR WORSE IMPROVED RESOLVED
NU
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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
0
5
10
15
20
25
SAME OR WORSE IMPROVED RESOLVED
NU
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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
02468
10121416
SAME OR WORSE IMPROVED RESOLVED
NU
MB
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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
02468
10121416
SAME OR WORSE IMPROVED RESOLVED
NU
MB
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F P
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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
02468
10121416
SAME OR WORSE IMPROVED RESOLVED
NU
MB
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S O
F P
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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
02468
10121416
SAME OR WORSE IMPROVED RESOLVED
NU
MB
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S O
F P
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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
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