From: rpautrey2 on

Excerpts From:
Iontopheretic System for Stimulation of Tissue Healing and
Regeneration
http://www.rexresearch.com/becker/becker1.htm

Abstract --- An iontophoretic system for promoting tissue healing
processes and inducing regeneration. The system includes a device and
a method, a composition, and methods for making the composition in
vitro and in vivo. The system is implemented by placing a flexible,
silver-containing anode in contact with the wound, placing a cathode
on intact skin near the anode, and applying a wound-specific DC
voltage between the anode and the cathode. Electrically-generated
silver ions from the anode penetrate into the adjacent tissues and
undergo a sequence of reactions leading to formation of a silver-
collagen complex. This complex acts as a biological inducer to cause
the formation in vivo of an adequate blastema to support
regeneration.

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Furthermore, electrically-injected silver ions are known to have
significant antibacterial and antifungal properties. Silver is a well-
known antibiotic, widely used in topical applications in the form of
silver nitrate solution, silver sulfadiazine, and so forth. However,
the useful antibacterial effect of such compounds is limited and due
only to the small amount of free silver ions produced by dissociation
of the compound or to formation of toxic by-products (for example, use
of silver nitrate (AgNO.sub.3) solutions may lead to the formation of
nitric acid). The antibacterial action of these ions is limited to a
very localized effect directly on the wound surface.

Electrically-generated silver ions, on the other hand, penetrate at
least approximately 1 cm into the wound and can be produced in much
larger amounts than is possible with topical preparations such as
silver sulfadiazine. Thus, electrically-injected silver is effective
even against antibiotic-resistant strains, inhibiting bacterial growth
in vivo and in vitro at current densities as low as 10 nA/mm.sup.2 and
concentrations as low as 0.5 mg/ml. Susceptible organisms include S.
aureus, E col., Candida and Torulopsis. These effects are described in
a number of publications, including the following: J. A. Spadaro, et
al., "Antibacterial Effects of Silver Electrodes with Weak Direct
Current," Antimicrobial Agents and Chemotherapy, Vol. 6, pp. 637-642
(1974); J. A. Spadaro and R. 0. Becker, "Some Specific Cellular
Effects of Electrically Injected Silver and Gold Ions,"
Bioelectrochemistry and Bioenergetics, Vol. 3, pp. 49-57 (1976); T. J.
Berger, et al., "Antifungal Properties of Electrically Generated
Metallic Ions," Antimicrobial Agents and Chemotherapy, Vol. 10, pp.
856-860 (1976); J. A. Spadaro and R. 0. Becker, "Experience With
Anodic Silver in the Treatment of Osteomyelitis," Proceedings of the
25th Annual Orthopedic Research Society Meeting, Vol. 4, p. 10 (1979);
R. 0. Becker, et al., "Treatment of Orthopedic Infections With
Electrically-Generated Silver Ions," Journal of Bone and Joint
Surgery, Vol. 60A, pp. 871-881 (1978).

At any particular silver concentration, electrically-generated silver
ions are more effective in inhibiting bacterial growth than silver
salts (T. J. Berger, et al., "Electrically Generated Silver Ions:
Quantitative Effects on Bacterial and Mammalian Cells," Antimicrobial
Agents and Chemotherapy, Vol. 9, pp. 357-358 (1976); Hall, et al.,
"Inhibitory and Cidal Antimicrobial Actions of Electrically Generated
Silver Ions," J. Oral and Maxillofac. Surg., Vol. 45, pp. 779-784,
1987).

Becker (U.S. Pat. No. 4,528,265) has disclosed processes and products
that involve subjecting mammalian cells to the influence of
electrically-generated silver ions. Anodic silver causes cells such as
mammalian fibroblasts to assume a simpler, relatively unspecialized
form and to resemble dedifferentiated or embryonic cell types. In
mammals, including humans, this effect is associated only with the
silver ions; the effect is not related to the electrical current or
voltage. The afore-mentioned publications are incorporated herein by
reference.

A variety of devices for use in electrical stimulation are known.
Liboff, et al. disclose a noninvasive magnetic field generator for
producing a controlled, fluctuating, directionally oriented magnetic
field parallel to an axis projecting though the target tissue (U.S.
Pat. No. 4,932,951). An externally-generated magnetic field can be
combined with the local magnetic field to produce a resultant field
that enhances transfer of ions such as Ca.sup.++ across the membrane
of a living cell (Liboff, et al., U.S. Pat. No. 4,818,697).

Other devices make use of the antimicrobial properties of silver and
other metals. Raad, et al. (U.S. Pat. No. 5,324,275) disclose a
catheter tube surrounded by two parallel helical conductors made of
copper, gold, silver or other heavy metals. When connected to a DC
power source such as a 9-volt battery, ions are transferred between
the conductors through body fluids, and induce an antimicrobial effect
proximate the area between the conductors.

Milder (U.S. Pat. No. 5,322,520) describes a material containing
dissimilar metal powders, such as silver and gold, silver and copper,
or silver and platinum mixed into a conductive polymer substrate. When
contacted by an electrolytic solution, each metal granule that
contacts the electrolyte becomes either an anode or a cathode, so the
material contains an array of small batteries. Metal ions are driven
into the solution to kill bacteria on and near a device to which the
material is affixed. The material can be used in devices such as
catheters, cardiac pacemaker leads, artificial; hip joints, and so
forth.

Seiderman (U.S. Pat. No. 4,767,401) describes a method for
iontophoretic administration of medicaments such as silver protein (a
colloid of silver with protein). The medicament is coated onto a
metallic foil electrode so that, when in contact with a wound, natural
body fluids and the negative electric charge of the wound site create
a voltaic effect that causes the medicament to migrate into the
wound.