cooper-treated dressings for wound healing

1. Joint Accessions Research and Best Practices Symposium – April 18, 2007
Innovative Technology For
Medicine
COPPER
Richard C. Zatcoff, D.P.M.
DABPS, FACFAS, FACFAOM

2. Historic 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.

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

4. Resistance to copper
While 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.

5. Copper
Benefits in Human Health

6. Essential Metals for Human Health
Copper Calcium
Cobalt Chromium
Iron Potassium
Magnesium Manganese
Sodium Nickel
Zinc

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

8. •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

9. Absorption
•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. 67.1998
Levenson, AM. J. CLIN. NOTR. 67.1998

10. Additional Properties of Copper
• Anti-bacterial
• Anti-fungal
• Anti-viral

11. Today soluble copper is used as a:
 Water Purifier
 Algicide
 Fungicide
 Molluscicide
 Bactericide

12. Question: Can non-soluble
copper have biocidal
properties?
Answer: Yes! Non-soluble
copper has potent biocidal
properties!

13. How the biocidal effect is
achieved?

14.  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 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

15. Water bridge
Copper molecule
ion release
The Simple Chemistry

16. Copper
ions
Damage bacterial
cell wall
Copper Oxide
Damage bacterial
DNA
Damage bacterial
proteinsBacteria/fungi

17. No Development of Resistant
Microbes!!

18. • Bacteria require Cu+1 and Cu+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

19. Cu+1 or Cu+2
CsoR- Settles back
on bacterial DNA
blocking further gene
transcription
CsoR
Bacterial DNA
CsoR Cu+1or Cu+2
Bacterial transcription - genes, leading to
a protein pump that kicks out copper
Decreased
Cu
Possible Primary Cu Sensing Protein in Majority of Bacteria
Giedroc D, Chem and Eng News, Dec 11, 2006, Vol 84: #50, pg 12

20. 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

21. Wound 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

22. Cupron Copper Gauze Pad
10cm x 10cm
3% Cupron
Gamma Irradiated

23. Copper Impregnated Gauze Pads by Cupron, Inc.

24. Start treatment 2Weeks of treatment
4Weeks of treatment 10 Weeks of treatment
71 YO WM Diabetic

25. 4 Months of treatment
Start treatment 2 Weeks of treatment
55 YO WF Diabetic
9 Months of Treatment
1-30-2007

26. 5 Months of treatment
2 Weeks of treatmentStart treatment
75 YO WM Diabetic,PVD

27. #160 04-03-06
3 months before treatment
2 months of treatment
12 months of treatment
81 YO WM Diabetic, PVD

28.  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

29. 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

31. X 200
X 1,500
Inclusion of Copper Oxide into
Polymeric Materials
• Polyester,
• Polypropylene,
• Polyurethane,
• Polyolefin,
• Polyethylene, and
• Nylon fabrics

32. In Vitro Studies
with Copper Treated
Fibers/Fabrics

33. Staphylococcus aureus
CFU per sample
103
104
105
106
120 min
0 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+

34. Escherichia coli
CFU per sample
103
104
105
106
120 min
0 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-

35. Cupron Fabric
0 1
hours
ColonyFormingUnits
101
102
103
104
105
Control Fabric
0 1
hours
Cupron Fabric
0 1
hours
Control Fabric
0 1
hours
MRSA VRE
Subcontract laboratory performing tests:
Hy Laboratories Ltd., Park Tamar, Rehovot 76325, Israel
Drug Resistant Bacteria

36. Candida albicans
minutes
0 10 20 30 40 50 60
numberoffungi
0
10000
20000
30000
40000
50000
60000
Anti-fungal Activity
Subcontract laboratory performing tests:
AminoLab Laboratory Services, Weizman Industrial Park, Nes Ziona 79400, Israel

37. 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
Is Very Well Documented

38. 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

39. Animal 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

40. X-Static Fiber Vs. Cupron Fiber
Candida albicans
Washing Cycles
0 5 10 20 25 50 100 1 2
ColoniesFormingUnits/sample
0
2000
4000
6000
8000
10000
12000
14000
X-Static
Cupron
Control fungi
control
fungi

41. 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

42. 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)

43. Introduction of
Copper Oxide
into
Cotton
Fibers
Copper
Fibers
Antifungal
Socks
Acaricidal
Mattress
Covers
Antibacterial
Garments
Athlete’s
foot,
Diabetics
Dust mite
allergies
Hospitals
(Nosocomial
Infections)
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
Polymer Layer
Polymer Layer
Fig 1. Basic Cupron filter design*

44. Copper Sole™ Socks
A Revolutionary Technology
Investigation by
Richard Zatcoff D.P.M.
Upstate Podiatry
Simpsonville, SC

45. September 2004 – January 2005
 N=56
 Males - 40
 Females – 16
 Diabetics – 21
 Ages 21 - 85

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

47. Contents
78% Polyester / 12% Cupron Polyester /
9% Nylon / 1% Lycra
Contents
81% Polyester / 11% Cupron Polyester /
7% Nylon / 1% Lycra

48. 56 Patient-Clinical Study*
Clinically Tested
 Patients were compared to historical controls.
 Patients with Cupron® yarn socks were observed for
improvement or resolution in the following conditions:
-Erythema -Vesicular eruptions
-Burning/itching -Fissures
-Scaling -Drainage
-Edema -Odor
*2004-2005 Study,
R.C. Zatcoff, D.P.M.
Upstate Podiatry,
Greenville, SC

49. Another 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.

50. 51 YO WF Diabetic
09-08 09-22

51. 09-08 09-22

52. 84 YO WM Diabetic
09-27 10-04

53. #1985 80 YO WM - Diabetic

54. #8045 72 YO WM

56. #9008 73 YO WM - Diabetic

57. #9679 58 YO WM

58. #9835 75 YO WM - Diabetic

60. #9871 67 YO WM

61. #8906* 49 YO BF - Diabetic

62. Mitigating Factors
 Participant Compliance – Wear Time
 Possible degradation of Cupron Fibers
 Persistent infection from nail reservoir
 Co-morbidity effects

63. A. ERYTHEMA (51 patients):
All 51 patients improved; 22 (42%) resolved completely over an
average period of 9 days (range 4-28 days). The 95% confidence
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
NUMBERSOFPATIENTS

64. A1. Longer term study (22 patients):
Nineteen (86%) maintained their improvement or resolved, 95% CI
(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-
up was 36 days. Diabetics and patients older than 65 shared in the
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
NUMBERSOFPATIENTS

65. B. SCALING (56 patients):
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,
1.00); for resolution (0.03, 0.20). Both of the p-values are highly
significant for efficacy.
SCALING, AVERAGE TREATMENT OF 9 DAYS
0
10
20
30
40
50
60
SAME OR WORSE IMPROVED RESOLVED
NUMBERSOFPATIENTS

66. B1. Longer term study (24 patients):
Twenty-one (88%) held improvement or resolved, 3 reverted with an
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
improvement.
SCALING, AVERAGE FOLLOW-UP 34 DAYS
0
10
20
30
40
50
60
SAME OR WORSE IMPROVED RESOLVED
NUMBERSOFPATIENTS

67. C.FISSURING (37 patients):
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.
FISSURING, AVERAGE FOLLOW-UP OF 10 DAYS
0
5
10
15
20
25
SAME OR WORSE IMPROVED RESOLVED
NUMBERSOFPATIENTS

68. C1. Longer term study (17 patients):
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
shared in the improvement.
FISSURING, AVERAGE FOLLOW-UP OF 39 DAYS
0
5
10
15
20
25
SAME OR WORSE IMPROVED RESOLVED
NUMBERSOFPATIENTS

69. D. BURNING OR ITCHING (23 patients):
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
(0.61, 0.95) with a p-value of 0.003, again highly significant.
BURNING OR ITCHING, AVERAGE FOLLOW-UP OF 8
DAYS
0
2
4
6
8
10
12
14
16
SAME OR WORSE IMPROVED RESOLVED
NUMBERSOFPATIENTS

70. D1. Longer term study (8 patients):
All 8 patients were unchanged over an average
follow-up of 46 days, meaning that their initial
improvement was maintained. The numbers were too
small to study diabetics and elderly.
BURNING OR ITCHING, AVERAGE FOLLOW-UP OF
46 DAYS
0
2
4
6
8
10
12
14
16
SAME OR WORSE IMPROVED RESOLVED
NUMBERSOFPATIENTS

71. E. VESICULAR ERUPTIONS (23 patients):
All 23 patients improved; 13 (56%) resolved
completely, 95% CI (0.34, 0.76).
VESICULAR ERUPTIONS, AVERAGE FOLLOW-UP OF
8 DAYS
0
2
4
6
8
10
12
14
16
SAME OR WORSE IMPROVED RESOLVED
NUMBERSOFPATIENTS

72. E1. Longer term study (10 patients):
All 10 patients maintained their improvement or
resolved (6) over an average follow-up of 45 days.
The proportions were similar for both diabetics and
patients over the age of 65.
VESICULAR ERUPTIONS, AVERAGE FOLLOW-UP OF
45 DAYS
0
2
4
6
8
10
12
14
16
SAME OR WORSE IMPROVED RESOLVED
NUMBERSOFPATIENTS

73. CONCLUSION
Compared to historical controls, patients with Cupron ® socks
had significant improvement or resolution in the following
conditions:
- Erythema - Vesicular eruptions
- Burning/itching - Fissures
- Scaling - Drainage
- Edema - Odor
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), this study is statistically significant for improvement or
resolved for all the above conditions for people with diabetes,
including elderly diabetics.
Statistical Review – Michael S. Smith, MD MS

74. 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

75. Aetrex Copper Sole Socks

76. Thank You