CA1113396A - Iontophoretic medicinal treatments of mammalian bodies and articles therefor - Google Patents
Iontophoretic medicinal treatments of mammalian bodies and articles thereforInfo
- Publication number
- CA1113396A CA1113396A CA282,068A CA282068A CA1113396A CA 1113396 A CA1113396 A CA 1113396A CA 282068 A CA282068 A CA 282068A CA 1113396 A CA1113396 A CA 1113396A
- Authority
- CA
- Canada
- Prior art keywords
- bandage
- electrode
- medicament
- collagen
- collagen fibrils
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
- A61L15/325—Collagen
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- Health & Medical Sciences (AREA)
- Hematology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Materials For Medical Uses (AREA)
- Electrotherapy Devices (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE:
The invention is concerned with a bandage adapted for application to a mammalian body having a wound, lesion or the like, which comprises: (a) a bandage substrate adapted for application to the body; (b) a single metallic electrode, at least a part of this electrode being in direct contact with the body; and (c) collagen and/or an ionizable or polar medi-cament in electrically co-operative relationship with the electrode. The bandage is capable in use of forming a galvanic couple between the single electrode and the body when applied over the wound, lesion or the like, and producing, without use of an external power source, a local current effective for iontophoresis or for applying a small electric charge to the body. The bandage of the invention has surprisingly been found to be capable of creating a galvanic couple between the single electrode on the one hand and the body of the mammal on the other. When this bandage is applied to a mammalian body, natural body fluids or applied electrolyte activate the bandage and the desired voltaic effect is created, which causes a medicament contained in the bandage to migrate deeply within a wound or lesion.
The invention is concerned with a bandage adapted for application to a mammalian body having a wound, lesion or the like, which comprises: (a) a bandage substrate adapted for application to the body; (b) a single metallic electrode, at least a part of this electrode being in direct contact with the body; and (c) collagen and/or an ionizable or polar medi-cament in electrically co-operative relationship with the electrode. The bandage is capable in use of forming a galvanic couple between the single electrode and the body when applied over the wound, lesion or the like, and producing, without use of an external power source, a local current effective for iontophoresis or for applying a small electric charge to the body. The bandage of the invention has surprisingly been found to be capable of creating a galvanic couple between the single electrode on the one hand and the body of the mammal on the other. When this bandage is applied to a mammalian body, natural body fluids or applied electrolyte activate the bandage and the desired voltaic effect is created, which causes a medicament contained in the bandage to migrate deeply within a wound or lesion.
Description
The present invention relates to the covering of a wound, lesion or the like on an animal body with an ad~
herent, skin-like collagen membrane to effect protection therefor during the healing process. The invention also pertains to an iontophoretic process whereby collagen fibrils are electrochemically linked with each other and to the wound or lesion site to provide such membranes.
The present invention further relates to the ion-tophoretic administration of topical or systemic ionizable or polar medicaments to a mammalian body, which medicaments are responsive to an e~ectric field, and more especially, to the administration of denatured or undenatured proteins, with :, ~ or without a metallic component, to a wound, lesion or the ~
~i .
like, under the influence of an electric field, most preferably a weak electric field. Additionally, the invention is relevant to therapeutic treatments of mammalian bodies by the applica-tion of minute electrical currents thereto. The invention also - relates to articles adapted for use in practicing the pxesent method.
The need to provide protection for a wound, lesion or the like on an animal body during the healing thereof has long been recognized. Bandages, surgical dressings and coat- ~ -ings are often used for this purpose. More recently, surgical grafting techniques have been developed to avoid the oxygen impermeability problems encountered with extensive use of bandage-like protective coatingsO Although skin grafting is quite successful when the patient'sown skin is used, grafts from donors often give rise to rejection _ - -2-' , 3~?~
problems preventing the proper therapeutic eEfects. Thus, other proteinaceous materials such as collagen have been employed in oxygen-permeable protective materials~:
In recognition o:E the highly favorable, inherent ,~
characteristics of collagen which render it adaptable for providing protective films for wounds, lesions and the like, I have developed a process for the formation of adherent films disclosed in my U.S. Pa-tent No. 3,563,228 issued ~ February 16, 1971. Briefly described, -that earlier patent `.
; 10 relates to the app.lication of an electric field, of .
suitable polarity, to a dispersion of undenaturated collagen fibrils to cause electrochemical-linking between the fibrils of the.dispersion. The collagen, thus applied, is also capable.of linking to native collagen fibrils exposed at the wound site to effect a highly adherent, protective surface thereover.
In recognlzing the advance over the prior art .
provided by my:U.S~. Patent No. 3,563,228, it would be ~:
deslrable to provide these adherent, skln-like protective coatings but without the need for application of an external -~
power source to provide the iontophoreti.c impetus thereEor, it being appreciated that the electric apparatus are often .:
bulky and, oftentimes require the patient to.be treated at some central location. Accordingly, it is.desirable to be ;~
able to provide~these protective coatings by continuous ~;
treatment of the patient without significant restrictions .
upon ambulation or the necessity of confinement. ~
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Further along these lines, the utility of an electric field in medical treatment is, of course, well ~;
known. For example, it has been commonplace to provide bandage-like articles with electrodes comprised of dis-similar metallic materials to create a galvanic cell for various types of clinical treatment. These ar~icles, conventionally termed voltaic plasters, have been devised for the iontophoretic administration of certain medicaments through a patient's skin. Note, for example, United States Patent Nos. 116,562, No. 175,974, No. 222,276, No. 393,741 and No. 1,967,927.
The prior art voltaic plasters suffer numerous significant disadvantages, however. Perhaps the most impor-~; tant are the tendencies towards metal poisoning and/or for electro~de burns due to the materials employed, chiefly based upon copper and zinc as the dissimilar materials for the galvanic cell.
Currently, when it is desired to iontophoretically administer topical medicaments, external power sources are employed. Note, e.g. United States Patent No. 3,163,166, as well as my earlier United States Patent No. 3,563,228.
Moreover, all prior art methods based upon the application of an electric field to the body have hitherto employed substantial voltages and/or currents which not only tend to be discomforting to the patient, bu~ can actually traumatize the area proximate the point of application.
Consequently, it is most desirable to provide a therapeutic iontophoretic treatment of mammalian bodies , ,; :
;3 3~;
.
.
which optimi~es the healing effect thereo while minimizing the highly deleteriou~ side ef~ects and eliminating the need for bulky external power sources.
This object is achieved, in accordanae with th~
invention, by providing a bandage adapted.for application to a mammalian body having a wound, lesion or the like~ which comprises:
(a) a bandage substrate adapted for applica~ion to the body; .
~b~ a single metallic electrode, at least a part of this electrode being in direct contact with the body; and (c) collagen and/or an ionizable or~polar medicament in electrically co-operative relationship with the electrode.
The bandage is capable in use of forming a galvanic couple between the single electrode and the body when applied .~ over the wound, lesion or the like, and producing~ without useof an external power source, a local current effective for ontophoresis or for applying a small electric charge to the ~ body.
: 20 Optionally~ should it be desired to efect such a protective coating more rapidly than is possible by employing only the inherent electrical characteristics of the body to be treated, an auxiliary power source may be supplied. In accordance with this embodimént, such an auxiliary power supply is in~orporated integrally with a bandage or dressing substrate :bèaring the collagen to be electrochemically-linked. This , - power source comprises a galvanic couple which employs, inter alia, natural body fluids as an electrolyte. The galvanlc interaction between electrodes will create an electric ~ield which provides the iontophoretic impetus for electrochemical-linking of the applied collagen to yield an adherent, skin-like protective layer thereof over the tissue area to be treated.
Surprisingly, it has also been ascertained that ionizable or polar medicaments may be effectively admin-istered to a mammalian body, when there is provided an iontophoretic impetus derived, in part, from these naturally-occuY~ring local charges on the body to ~e treated ; 10 in concert with a similar compatible electrode borne upon or comprising a bandage or bandage-like substrate. This embodiment is efficacious for the administration of any îonizable or polar medicament responsive to an electric field; proteinaceous medicaments, or derivatives thereof, being preferred. The proteinaceous medicaments may be either undenatured or denatured, e.g., the protein component of mild or strong silver protein, alginates, and the like. ;
Additionallyj there may be present various matallic salts or compounds, partlcularly when a denatured protein iS ,
herent, skin-like collagen membrane to effect protection therefor during the healing process. The invention also pertains to an iontophoretic process whereby collagen fibrils are electrochemically linked with each other and to the wound or lesion site to provide such membranes.
The present invention further relates to the ion-tophoretic administration of topical or systemic ionizable or polar medicaments to a mammalian body, which medicaments are responsive to an e~ectric field, and more especially, to the administration of denatured or undenatured proteins, with :, ~ or without a metallic component, to a wound, lesion or the ~
~i .
like, under the influence of an electric field, most preferably a weak electric field. Additionally, the invention is relevant to therapeutic treatments of mammalian bodies by the applica-tion of minute electrical currents thereto. The invention also - relates to articles adapted for use in practicing the pxesent method.
The need to provide protection for a wound, lesion or the like on an animal body during the healing thereof has long been recognized. Bandages, surgical dressings and coat- ~ -ings are often used for this purpose. More recently, surgical grafting techniques have been developed to avoid the oxygen impermeability problems encountered with extensive use of bandage-like protective coatingsO Although skin grafting is quite successful when the patient'sown skin is used, grafts from donors often give rise to rejection _ - -2-' , 3~?~
problems preventing the proper therapeutic eEfects. Thus, other proteinaceous materials such as collagen have been employed in oxygen-permeable protective materials~:
In recognition o:E the highly favorable, inherent ,~
characteristics of collagen which render it adaptable for providing protective films for wounds, lesions and the like, I have developed a process for the formation of adherent films disclosed in my U.S. Pa-tent No. 3,563,228 issued ~ February 16, 1971. Briefly described, -that earlier patent `.
; 10 relates to the app.lication of an electric field, of .
suitable polarity, to a dispersion of undenaturated collagen fibrils to cause electrochemical-linking between the fibrils of the.dispersion. The collagen, thus applied, is also capable.of linking to native collagen fibrils exposed at the wound site to effect a highly adherent, protective surface thereover.
In recognlzing the advance over the prior art .
provided by my:U.S~. Patent No. 3,563,228, it would be ~:
deslrable to provide these adherent, skln-like protective coatings but without the need for application of an external -~
power source to provide the iontophoreti.c impetus thereEor, it being appreciated that the electric apparatus are often .:
bulky and, oftentimes require the patient to.be treated at some central location. Accordingly, it is.desirable to be ;~
able to provide~these protective coatings by continuous ~;
treatment of the patient without significant restrictions .
upon ambulation or the necessity of confinement. ~
':
;' ' . , :. '~
- ' :
; '.i .
Further along these lines, the utility of an electric field in medical treatment is, of course, well ~;
known. For example, it has been commonplace to provide bandage-like articles with electrodes comprised of dis-similar metallic materials to create a galvanic cell for various types of clinical treatment. These ar~icles, conventionally termed voltaic plasters, have been devised for the iontophoretic administration of certain medicaments through a patient's skin. Note, for example, United States Patent Nos. 116,562, No. 175,974, No. 222,276, No. 393,741 and No. 1,967,927.
The prior art voltaic plasters suffer numerous significant disadvantages, however. Perhaps the most impor-~; tant are the tendencies towards metal poisoning and/or for electro~de burns due to the materials employed, chiefly based upon copper and zinc as the dissimilar materials for the galvanic cell.
Currently, when it is desired to iontophoretically administer topical medicaments, external power sources are employed. Note, e.g. United States Patent No. 3,163,166, as well as my earlier United States Patent No. 3,563,228.
Moreover, all prior art methods based upon the application of an electric field to the body have hitherto employed substantial voltages and/or currents which not only tend to be discomforting to the patient, bu~ can actually traumatize the area proximate the point of application.
Consequently, it is most desirable to provide a therapeutic iontophoretic treatment of mammalian bodies , ,; :
;3 3~;
.
.
which optimi~es the healing effect thereo while minimizing the highly deleteriou~ side ef~ects and eliminating the need for bulky external power sources.
This object is achieved, in accordanae with th~
invention, by providing a bandage adapted.for application to a mammalian body having a wound, lesion or the like~ which comprises:
(a) a bandage substrate adapted for applica~ion to the body; .
~b~ a single metallic electrode, at least a part of this electrode being in direct contact with the body; and (c) collagen and/or an ionizable or~polar medicament in electrically co-operative relationship with the electrode.
The bandage is capable in use of forming a galvanic couple between the single electrode and the body when applied .~ over the wound, lesion or the like, and producing~ without useof an external power source, a local current effective for ontophoresis or for applying a small electric charge to the ~ body.
: 20 Optionally~ should it be desired to efect such a protective coating more rapidly than is possible by employing only the inherent electrical characteristics of the body to be treated, an auxiliary power source may be supplied. In accordance with this embodimént, such an auxiliary power supply is in~orporated integrally with a bandage or dressing substrate :bèaring the collagen to be electrochemically-linked. This , - power source comprises a galvanic couple which employs, inter alia, natural body fluids as an electrolyte. The galvanlc interaction between electrodes will create an electric ~ield which provides the iontophoretic impetus for electrochemical-linking of the applied collagen to yield an adherent, skin-like protective layer thereof over the tissue area to be treated.
Surprisingly, it has also been ascertained that ionizable or polar medicaments may be effectively admin-istered to a mammalian body, when there is provided an iontophoretic impetus derived, in part, from these naturally-occuY~ring local charges on the body to ~e treated ; 10 in concert with a similar compatible electrode borne upon or comprising a bandage or bandage-like substrate. This embodiment is efficacious for the administration of any îonizable or polar medicament responsive to an electric field; proteinaceous medicaments, or derivatives thereof, being preferred. The proteinaceous medicaments may be either undenatured or denatured, e.g., the protein component of mild or strong silver protein, alginates, and the like. ;
Additionallyj there may be present various matallic salts or compounds, partlcularly when a denatured protein iS ,
2~ employed~ That metallic ion most preferred is silver,;
albeit, other medicinally-effective metallic ions may be incorporated.
The bandage or bandage-like device employed to deliver the medicament to the mammalian body has an integral ~, 25 electrode of, e.g., foil in electrically-cooperative rela- ;~
tionship with the medicament thereon. Aluminum is the most ." ' ~
preferred electrode material; howe~er, the electrode might ~ be fabricated from any of a number of known active materials~ -~
;- -6-.. ,. ~:
, When the device, comprised of the electrode and medicament, is applied to a mammalian body, natural body fluids or, optionally, administrated isotonic or other electrolytic fluids, will establish the appropriate electric ~-current and concomitant field for delivery of the medicament deep within the wound, lesion, or the like, on ~he body.
The medicaments envisioned for use in conjunction with this invention comprise, but are not limited to, anti-infective, analgesic, bacteriostatic, and like ionizable or polar compounds, provided the compound is responsive, in terms of migration, to an electric field.
In yet another embodiment, it has been further surprisingly discovered that highly beneficial therapeutic effects may be realized from the application of exceedingly slight or minute electrical currents, for periods from as short as about 10 minutes to longer term treatments ranging up to a few weeks, the period of time and amount of electri-cal current applied generally varying inversely. The thera~utic effects are realized by applying a current within the range of from about 0.001 to about 1,000 micro-amperes (~iA), and most preferably from about 2.5 to about S00 microamperes, at a voltage of from about 0.01 to about
albeit, other medicinally-effective metallic ions may be incorporated.
The bandage or bandage-like device employed to deliver the medicament to the mammalian body has an integral ~, 25 electrode of, e.g., foil in electrically-cooperative rela- ;~
tionship with the medicament thereon. Aluminum is the most ." ' ~
preferred electrode material; howe~er, the electrode might ~ be fabricated from any of a number of known active materials~ -~
;- -6-.. ,. ~:
, When the device, comprised of the electrode and medicament, is applied to a mammalian body, natural body fluids or, optionally, administrated isotonic or other electrolytic fluids, will establish the appropriate electric ~-current and concomitant field for delivery of the medicament deep within the wound, lesion, or the like, on ~he body.
The medicaments envisioned for use in conjunction with this invention comprise, but are not limited to, anti-infective, analgesic, bacteriostatic, and like ionizable or polar compounds, provided the compound is responsive, in terms of migration, to an electric field.
In yet another embodiment, it has been further surprisingly discovered that highly beneficial therapeutic effects may be realized from the application of exceedingly slight or minute electrical currents, for periods from as short as about 10 minutes to longer term treatments ranging up to a few weeks, the period of time and amount of electri-cal current applied generally varying inversely. The thera~utic effects are realized by applying a current within the range of from about 0.001 to about 1,000 micro-amperes (~iA), and most preferably from about 2.5 to about S00 microamperes, at a voltage of from about 0.01 to about
3.0 volts. The beneficial effects observed range from healing of wounds, lesions, or the like by the linking of exposed, damaged collagen fibrils, to actual regeneration of tissue materials following, for example, surgery, and the improved knitting of bone frac-tures. Attendant this thera-peutic effect is a substantial diminution in pain commonly .
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I encountered in these situations.
FIG. 1 is a top elevation view of a bandage according to one embodiment of the present invention;
FIG. 2 is a side elevation view of the bandage of FIG. 1;
FIG. 3 is a side elevation view, similar to that of FIG. 2, showing an alternate embodiment of the present invention;
FIG. 4 is a botkom elevation view of a bandage according to yet another embodiment of -the present inven-tion; and ` FIG. S is a slde elevation view of the bandage of FIG. 4.
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In order to more fully elucidate upon the objects 15 and advantages of the present invention, the following detailed description will be given in terms of various pre- ~-ferred embodiments and exemplified~with respect thereto.
; ~ The same are intended, however, to be illustrative and in ; no wise limitative.
Furthermore, as used in the context of the present I invention, the term bandage is meant to include all ; varieties of surgical dressings, regardless of physical , configuration, which may be applied over a wound site to : ~, effect treatment therefor. Thus, the present invention t envisions utility extending from the rather small adhesive ~;l bandages to large dressings o~ several squate feet which ~ -8- ~
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may be applied to burn victims.
The first embodlment to be described makes use of the inherent, negative electrlcal potential of an animal body to provide the necessary iontophoretic impetus for electrochemical-linking of collagen fibers contained in a dispersion applied proximate the area to be treated. To achieve these ends, a collagen dispersion is prepared in the same ma~ner as that described in U. S. Patent No.
3,563,228, save for the fact that the collagen concentra-- lO tion in the instant dispersion is greater than the pre-ferred 0.25% to 1% by weight concentration recited therein, e.g., up to about 50% by weight concentration, but most desirably having the consistency of soft table butter.
More specifically, the instant collagen suspension may be ' 15 prepared from bovine deep flexor tendon which has been cleaned and trimmed of fat and other extraneous matter, frozen, and subsequently sliced perpendicular to the longi-tudinal axis of the tendons to a suitable length of about , O.001 mm to 0.5 mm, pref~erably from 0.2 mm to 0.5 mm, albeit ;
such a length is not critical. The collagen ~ibriis may , ~ ~
then be disaggregated by treatment with proteolytic enzyme such as commercial ficin. This treatment may be achieved, for example, by gentle aggitation for approximately 1 hour at 35F in an aqueous solution of ficin. These fibrils ~ ~
25 are then washed with distilled water and treated with ;
aqueous sodium chloride solution of appro~imately 1~ con-centration for about 1 hour in two or three successive treatments. See further said U. S. Patent No. 3,563/228.
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Having thus been prepared, these fibrils are added to a mixture of equal parts of ethanol and water, optionally containing approximately 0.2% cyanoacetic acid if long-term storage is anticipated; this mixture is then aggitated at a temperature approaching the freezing point thereof and sub-sequently homogenized by a conventional homogenizer.
Optionally, the collagen dispersion may be produced accord- f ing to the teachings of either U. SO Patent No. 3,368,911 -or the process of Battista as described in the ~ournal of 10 Applied Poly~er Science, 11, 41-498 (1967).
Such a dispersion of, for example, 10% collagen concentration, will exhibit a paste-like or syrupy consistency, -~; sometimes similar to that of soft butter. This paste or dis-persio;~ is then enhanced for better conductivity by additions of saline (usually in amounts ranging from between 0.1% to 1.0~ by weight), such as sodium ~hloride or potassium chloride, ` preferably in amounts to render the paste isotonic; that is, ; 0.9~. Metallic salts corresponding to those indigenous to ; the animal body may also be added in similar minute quantities, ~ 20 e.g. in amounts ranging between about 0.01~ and 10~ by weight.
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~`I Selection of these salts, specifically to be rich in positive ions, is well within the purview of the skilled artisan.
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~} This paste may then be applied locally over the ~
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area to be treated. An electrical field will be established I~ 25 between the collagen paste dispersion and the animal body;
`f the paste will exhibit an overall positive char~e while the :.~1 . ` '.:
~ areas surrounding the wound site will exhibit an effective . ,~, j ~
-~ negati~e electrical potential. However, the relative ~f 1 .
. ~
,., ~, :
electrical potential thus established is relatively slight and, thus, the desi~ed electrochemical-linking of the collagen fibrils proceeds rather slowly. Accordinglyl it may be desirable to provide an auxiliary power source, operatin~ in conjunction with the body's inherent electri-cal characteristics, to enhance this action.
Figures 1-3 illustrate another embodiment of the present invention wherein a galva~ic couple is employed to achieve the necessary electrical impetus for electrochemical-linking. Figure l illustrates a bandage, generally design-nated as 10, bearing electrodes ll and 12. The bandage may be selected from numerous commercial varieties well known ~;
; to tnose skilled in the art and is necessary only to pro-vide a suitable substrate upon which the galvanic electrodes may be deposited, as well as a suitable quantity of collagen.
Preferably, the bandage will be comprised of a liquid ~; impervious top layer 13, as shown in Figures 2 and 3, possessing an area 14 wherein a plurality of perforations .. ...
I~ 16 are located~ Characteristics such as flexibility, `, 20 absorbency, etc., will be dictated by individual cases and t .:
~ are well known to the skilled artisan.
"., .
Electrodes ll and 12, which form the galvanic ~;
; couple, may be fabricated from strips of suitable electro-, chemical material, such as metal. The electrodes may be `. ! . .
25 adhered to the upper surface of the bandage in any desired manner, such as adhesive paste. Optionally, these electrodes may be fabricated by dispersing the desired electrochemi-cally-active material in a volatile carrier to form a for-mulation which may then be applied to the bandage. A
quantity of dry electrolyte 18 is disposed intermediate ~ ~-electrodes 11 and 12.
As viewed in Figure 2, a collagen coating, such as that fully described hereinabove, designated as 20, is applied to the opposite side of the bandage and dried.
; Electrode 12 is caused to be maintained in electrical contact with the collagen coating by internally disposed conductive member 19, although electrode 12 may be over-wrapped about the end of the bandage thereby providing this desired electrical contact. Electrode 11 is caused to be electrically insulated from both electrode 12 and the collagen coating 20 and lS overwrapped about the bandage 10 or otherwise caused to make electrical contact with the 15 skin of the animal to be treated at a location apart from ~
the wound area, W. ~;
It is necessary that electrode 12 exhibits a :i positive standard reduction potential with respect to ~` electrode ll to efect the proper polarity therebetween;
that is, current should flow from electrode 12, through the coated collagen layer to the tissue area of interest, and thence to electrode 11, through electrolyte 18 and back to electrode 12 to complete the electrical circuit, as depicted 'l in Figure 2. Thus, if the positive strip 12 is made of a metal which may be strongly attacked by electrolysis, it may , ,.
enter the wound, lesion, etc.. Accordingly, while the electrode 12 may be fabricated from any harmless metal, such as, aluminum, it is preferred that this positive r- - -12-:: - ", ..:: :.,:; :: .;: ,~:
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electrode be made from carbon. As regards the composition of electrode 11, any metallic material meeting the fore-going standard reduction potential criterion and one which further exhibits a harmles~ effect on the body may be -, suitably employed.
The bandage according to this embodiment may b-activated by applying a few drops of water to the perforated area 14 which will we-t both the electrolyte 18 and the dried collagen dispersion coating 20. Optionally, the -body's own fluids, such as blood or serum, may be employed to these endsO Once this has been achieved, galvanic action between the two electrodes will assist the inherent ~ ~egat~ve potential o the animal body by providing a current -~ of proper polarity and attendant electric field to aug~ent ~/ 15 that naturally existing~ Accordingly, collagen in the :
hydrated coating will electrochemically-link according to the lines of electric force, E, and the fibrils will form a film or membrane linked with damaged fibrils of the wound to effect an adherent, skin-like protective coating.
` ! : :
~ An alternate embodiment of the topic bandage is depicted in Figure 3 wherein there is now incorporated a :,. . . .
discrete region 22 which is porous in nature. In this embodiment, the material from which the bandage is fabricated ; .
~; is such ~hat the~collagen dispersion described supra may ~` 25 be impregnated therein; for example, foamed polyurethane, , Otherwise, this bandage will operate identical to the ~;
description for the bandage described in Figures 1 and 2.
3~
Further, it will be obvious to the skilled artisan that the bandage depicted in Figures 1-3, and described above, need not employ the saline or metallic salt com-ponents in the collagen dispersion during initial processing thereof. The action of the galvanically generated electric field will, in some cases, be sufficient to supplant the requirement of these constituents by using the body's own fluid components~
Another, and the most preferred embodiment in 10 accordance with the present invention is illustrated in ~ ~;
Figures 4 and 5~ In Figure 4, there is shot~ a bandage generally designated as 40 bearing an area 42 which is a -; film of electrochemically-active material. Borne upon the film 42 is a film of collagen 44. The electrical potential is derived fxom a single active electrode, 42, which i.s in ~; contact with ~he skin of the patient to be treated proximate -~
~' the wound area. The electrode 42 is chosen to ensure ~f~
it possesses negative electrical characteristics with respect i to the collagen film, as shown in Figure 5.
- 20 The materialsl selection for electrode 42 is ;~l restricted primarily upon considerations such as standard reduction potential to ensure the electrode maintains a negative potential with respect to the collagen film; the , , ~
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propensity for dissolution, to minimize the introduction of the electrode material within the wound area, as well as other considerations well known to the skilled artisan.
Preferred electrode materials are, for example, aluminum, 5 mild silver protein and zinc. However, when zinc is employed, due to its galvanic activity, it is preferable to form electrode 42 as a narrow strip adjacent collagen film 44, in contradistinction to the film shown in Figure 4, wherein the electrode is adjacent the entire periphery of collagen film 44.
~`~ Particularly beneficial results may be realized upon employing a mild silver protein film for electrode 42.
~, ~ild silver protein, a colloidal solution prepared by the :.~ . ,.
interaction of protein and silver oxide and containing about 15 l9 to 23% silver, is a well known bacteriostatic agent. `~
Only a small fraction of the silver is in an ionizable ,::
" state and, thus, mild silver protein is not irritating but, , ln fact, is somewhat demulcent. For a more comprehensive ~, understanding of the uses and~effects of mild silver protein, see Goodman and~Gillman. The Pharmacological Basis of Therapeutics, 3rd Edition, McMillan, 1969.
The mild silver protein membrane may be fabricated ~!
to exhibit either a propensity to disintegrate in moisture or, with good wet strength to preclude such occurrence.
25 Accordingly, the electrode material itself may take an active role in the healing process~
Another of the preferred electrode materials is ; aluminum, a relatively innocuous material with little _ f 5~
:
tendency to dissolve when the bandage is employed. A
bandage similar to that depicted in Figure 5 was fa~ricated for purposes of experimentation. The bandage 40 has an ~;
upper, liquid imper~ious layer 46 and conveniently possesses a pressure sensitive adhesive (not shown) on the obverse side in order to facilitate adherence of the bandage to ~he area for treatment. This test employed a conventional bandage commercially marketed undex the trademark CURAD.
A thin foil of aluminum, for example, 0.002 to 0.003 inches thick, was adhered over a gau2e area 50 of the bandage. A
paste of collagen was prepared in accordance wiih the process described above and deposited over the electrode 42 by means of a doctor blade. The collagen membrane, 44, may ~ r~
?.~
''!^`~ be either supported or unsupported, and may be processed to yield the collagen dispersible or insoluble in water, as desired. Once the bandage was assembled as shown in Figure 5, a drop of saline solutîon was placed upon the collagen ~l~ film. Potentiometric tests were performed upon the bandage at that time and indicated a voltage of 0.5 volts between the electrode and collagen film, and a current of 400 micro-amperes.
Other bandages were fabricated in similar fashion . .
employing electrode materials as set forth in Table I. The voltage and current developed by each of these bandages is - ;
25 likewise set forth in Table I~ ~
,:
, :
-16- ~ ;
.. . .
,.. . ,.-. . ., .; , :: :. ,.. -., . .. : : . . , -:~:
. -.- , . . , . . .. ,....... , ~.. .. .
.3 TABLE I
Electrode MaterialVoltage (V)Current (ua?
Aluminum 0.5 400 Zinc 1.2 200 Tin O.S 50 Titanium 0.15 25 Tantalum 0.1* 2.5 *reverse polarity ` :,:,,:
It has been observed that the collagen dispersion `I 10 borne upon the bandage substrate electrochemically-links ~i in a very short amount of time under the influence of the electrical potential derived from the galvanic source. More-over, the collagen film adherently and tenaciously attaches i to the wound site through both mechanical and chemical link--l 15 ~ages with the exposed, damaged collagen fibrils of the wound.~ Accordlngly, it has further been observed that the handage~substrate~itself may be removed in~a relatively short amount of time, leaving ~ehind this highly adherent, skin-Iike collagen film. Moreover, it has been observed `~
that the collagen film thus applied to the wound site, upon limited dehydration, will contract somewhat and tend to close the wound in a natural manner. These, and other benefits, are realized upon application of materials totally ~` -17-acceptable to the animal undergoing treatment and, accord-ingly, rejection is rare.
Moreover, various modifications may be made to the bandage and/or collagen dispersion of the present inven-tion. For example, mild silver protein may be mixed with ; the collagen dispersion to form a paste of enhanced electro-~; chemical activityO Further, the conductivity of mild silver protein has been found -to be enhanced by a rine spray or il .
~^ mist of ammonia prior to use. Thus, the relative electrical ;~ ~
. , ~ 10 potential between electrodes and~or the collagen f.ilm is ' `; ; ,~ ' : .
capable of a wide range of selection in order that the bandage be adapted ~or tailor-made operation. This is particularly true as the electrochemical-linking phenomenon ~ is a strong function of electrical potential and may be $
15 advanced or retarded based upon materials selection. ~^
It has also been determined that the notable benefits of practicing the presènt invention may be realized -~
: ~ ;
- ~ by impregnating simple tissue paper with the appropriate collagen dlsperslon, with or without additions, rather than ; ;~
``~ 20 ~depositing the~collagen upon a conventional bandage sub-strate. The impregnated paper, whether readily disinte-gratable or possessing wet strength, may then be utilized ~
for treatment, optionally in combination with any of the ~;
galvanic sources described above. In like vein, the collagen dispersion, with~or without additions, may be dried to a film, supported or unsupported, and used without need of any substrate. These~embodiments may prove highly ~eneficial ~``
for treatment of exte~nsive wound areas such as, for example,burns "`
Also, the collagen film may be electrically linked prior to its application to the wound area. Thus, the pre-linked film or membrane may be placed over the area to be treated and one of the foxegoing galvanic sources ; 5 applied to effect linking between the collagen membrane and damaged collagen fibrils of the wound.
~nother embodiment of the present invention per-~ains, broadly, to methods for the iontophoretic administra-~;`` tion of various ionizable or polar medicaments to a mammalian body and a delivery system therefor based upon a bandage such as the one described above~ More specifically, the ~
present invention is particularly adapted for the administra- ;
tion o~ various pxoteinaceous and/or biocompatible metallic medicaments, or derivatives thereof, to a mammalian body ~, 15 from a bandage or bandage-like article under the }nfluence ;~ .~- of an electric field established between the bandage and the body.
~, It is observed that prior art voltaic plasters , ~,;
suffer numerous disadvantages, the most significant being ~` 20 risk of metal poisoning and/or electrode burns to the body being treated due to the construction of the bandage from highly active dissimilar metals as the galvanic electrode materials, and an inability to effectively deliver a wide range of medicinally effective medicaments. Both of these significant drawbacks are overcome by the present invention, by providing an integral electrode on a bandage substrate hav-ing a quantity of medicament also borne thereon. When applied to mammalian body, natural body fluids or applied isotonic fluids will create a voltaic effect whereby the medicament is caused to migrate deeply within a wound, lesion, or the like, to elecit its desired pharmacologic response.
In part, the improvement derived from the present invention is coupled with the recognition that a mammalian body possesses a slight, inherent negative electric charge, ~ particularly at areas proximate the site of a wound, lesion ~ :
.~ or the like. Thus, by appropriate design of a delivery ` 10 device, materials may be employed which advantageously .~ utilize this electrica~ characteristic thereby overcoming the need for disslmilar electrodes to effect the galvanic ::
'i!~ cell while yet providing for the generation of a suitable ~.
-. electric field fox :the iontophoretic impetus. The improve-ment in the iontophoretic administration of medicaments in accordance with the present invention lies also, in part, in administering a broad range of ionizabIe or polar compounds ~ :
responsive to the applied el.ectric field. ~`
. : ~ : ;
;~~ : Whlle numerous anionic, cationic, and polar medi-20~ caments, including certain amphoteric medicaments, are envisioned within the scope of the present invention, the preferred are proteinaceous medicaments, eithex undenatured : or denatured. Thus, these preferred medicaments include -,~"
. the protein component of mild or strong silver protein, ~.
: 25 alginates, and the like. Additionally, various effective metallic salts may be employed in the iontophoretic admini- :
: stration method according to the present invention in con~
junction with the;protein or derivative thereof. It has : "
_~o_ :
, :
:
been determined that the proteinaceous medicament may be employed alone when the protein component is not denatured.
;; When, however, that protein component is denatured, it is particularly beneficial to employ a metallic salt, most ;~
preferably a silver salt. However, other medicinally-~- effective equivalent metallic salts might be utilized. ~-~; Likewise, other medicaments including, particularly, Dexamethasone Sodium Phosphate, Methylprednisolone Sodium ~ Succinate, Flurandrenolide, and Amphotericin, are preferred ;~ 10 compounds for use in conjunction with the present invention.
These compounds may be employed individually or in admixture, -~
with or without the additional presence of metallic salts, or denatured or undenatured mild silver proteins. Moreover, ., other various steroids, antibiotics, and antifungal com-pou~ds, or the like, may also be employed, together or separ-ately as might be desired. Further medicinally-effective ..
compounds and preparations may be selected from -s~ecific ;
pharmacological efects, such selection being within the scope of those skilled in the art.
The most preferred proteinaceous medicament is the antiseptlcally-effective mild silver protein, which is a colloid of silver with protein, containing on the order o about 10 to 25~ silver. This material is readily available, commercially; and is described in "The Merck Index", Merck 25 & Co., Inc., 5th Edition, 1940, page 458. However, other -anti-infectious, analgesic, bacteriostatic, and like proteinaceous compounds may be employed to this end.
In electrically-cooperative relationship with the _ -21-3~
medicament is an electrode, which may assume any of a number of physical configurations. Most preferably is a metallic foil, although any electrochemically-active material may be utilized and may be deposited in the form of a liquid j`
such as, for example, dispersion, and subsequently dried.
The electrode material should be selected from those known to be compatible with the mammalian body for the obvious -~
reasons including toxicity, irritation, etc. As will become more apparent hereinbelow, a salient distinction between the bandage of the present invention and those of the prior ,. }
-~ art is the absence of a galvanic couple of active metallic j ~ , `1 components on the bandage su~strate to which has been attributed the significant problems of electrode burns and/
~,'JI~or metal poisoning indigenous to the latter. That is, the instant-bandage employs but a singular electrochemically~
aetive material for the eleetrode, regardless of the physical ~ `
, ,~
state or configuration thereof, i.e.~ a bandage such as illus~
`~ trated in Figures 4 and 5. Of course, for the iontophoretic administration of certain of;the medicaments within the scope .. . ~
of the present invention, particularly those not heretofore , : . j iontophoretically administered (espeeially proteinaceous and ~ ;
protein/metallic medicaments), a conventional galvanic ;~
couple might be employed, e.g., a bandage such as illustrated in Figures 1-3. However, in seleetion of the appropriate materials for the couple, the skilled artisan will readily ~`
appreciate that less active metallie eomponents than utilized in prior art devices may well be ehosen due to the augmentive nature of the instant bandage respecting the ~- - ~22-.. .
33~
inherent electrical characteristics of the mammalian body to which the bandage will be applied.
; The most preferred electrode is a foil of aluminum metal. Other electrode materials include, for example, 5 copper, zinc, tin, and titanium, each of which will provide ~
an effective positive charge with respect to the mammalian ~;
- body. Should the medicament utilized require a net negative charge to provide the desired iontophoretic impetus of ~` proper polarity, such materials as tantalum might be utilized 0 Regardless of the electrode material or configura-tion thereof, it is essential that the electrode be in electrically-cooperative relationship with the medicament to be iontophoretically administered. As a consequence when the bandage is activated by electrolytic fluids such as, for example, body fluids or administered isotonic saline, voltaic interaction wlll establish an electric field between the electrode and underlying wound site and generate a corresponding electric current, whereby the ~;
medicament is caused to migrate deeply within the wound in ~
;!~ : ~ ,. . ...
20~ response thereto.
The present invention envisions utility extending -from small adhesive bandages to large dressing of several square feet which may be applied to, for example, burn victims. Exemplary of a particularly suitable bandage is that of Figure 4, denoted generally as 40, which is com~
:~ .
prised of, e.g., a 6" x 2" substrate 46, having a medial ~;
portion and terminal portions. The medial portion has adhered thereto a foil of, for example, aluminum metal, _ _~3--`' ~' 3~
denoted as 42. The foil optimally comprises approximately ~ ~
one half of the total surface area of the bandage substrate; ~; -~' however, these dimensions are not critical provided the electrode material has sufficient surface area to provide ; 5 the required iontophoretic effective electric current.
The central portion of the electrode 42 has I~ coated thereon, or adhered thereto, a quantity of the -~
;~ desired medicament 44. Preferably, the medicament is applied as a paste or liquid to some absorbent material ~
~, 10 such as tissue paper or sterile cloth or gauze. The medica~ ;-ment is allowed to dry and the porous carrier adhered to , the foil electrode.
`1 An optional embodiment employs a commercially- -available surgical bandage, such as those marketed under the trademark "CURAD". As opposed to the bandage of Figure 4, which may be made in relatively large dimensions, and ~
wherein the terminal portions may or may not be coated with ~`;
an adhesive substance, this altexnate embodiment is designed ~ `
.
~ ~for application to rather small cutst abrasions or the like.
:.
The bandage is comprised of a plastic or polymeric substrate having a medial portion and adhesively coated end portions with an absorbent gauze adhered to the substrate in the -medial portion. Two foil electrodes, such as 42' shown in Figure 4, are also borne upon the substrate and are caused 25 to partially~overlap the medial gauze area. The desired ~ -~
medicament may be applied to the gauze pad and allowed to dry.
~` A bandage in accordance with this latter embodiment '. ~
_ -24- ;
- `'- :.
was prepared in order to ascertain the effectiveness of the iontophoretic administration of mild silver protein to a human body. The bandage employed is approxlmately 7.5 cm long and 2.5 cm wide. The gauze pad accounts for approxi-5 mately 30% of the total surface area of the bandage and iscoated with a solution of mild silver protein (USP) made isotonic with 0.9% sodium chloride. After the medicament has dried, two rectangular strips of aluminum oil having dimensions of about 2.5 cm x 2.0 cm are adhered to the bandage substrate, partially overlapping the coated gauze area such that approximately 15~ of each aluminum foil strip is in direct contact with the coated gauze pad.
This bandage was placed on a human body over a minor wound. A drop o isotonic saline was administered to ~`~
lS the coated gauze pad in order to establish voltaic action between the aluminum foil electrodes and the body. The electric potential was measured to be about 3/4 of a volt, and the current generated about 10 microamperes. In response to the electric field thus generated, the silver protein .
medicament~migrated deeply within the wound at a rate much greater than wére the electric field absent.
A similar bandage was prepared employing as a ;substrate, a commercially-available bandage, marketed under the name "Air-Vent Tape Clear", by Johnson & Johnson.
;25 This bandage, measuring about 9.0 cm x 2.6 cm, was placed with the adhesive side-up, upon which was adhered, in the -~
central portion thereof, a foil of aluminum me~al measuring about 4.5 cm x ~2.0~cm x 0.0254 mm. The adheslve of the ,:
3~ r bandage provided suficient area for firm attachment of the foil thereto, leaving a sm~ll peripheral strip of adhesiye exposed along the longitudinal edges of the foil due to its narrower transverse dimension relative to that of the bandage.
Sterile tissue paper, measuring 2.4 cm x 2.4 cm, was soaked in a 10% solution of mild silver protein made .
isotonir with 0.9% sodium chloride. The tissue was removed ;~
: :
from this solution and permitted to dry. Subsequently, the impregnated tissue was placed over the aluminum foil, the exposed adhesive from the bandage providing means for firm ;~
`~ attachment.
This bandage was applied over a cut on a human ~' body, perspiration and wound serum providing the re~uisite 15 poly-electrolyte. The voltage of the resultant electric ~;
field was measured at about l volt; the current varied between 5 and 15 microamperes as the iontophoretic process ~;;
proceeded to carry the medicament deeply within the wound.
Depending upon the configuration of the electrodes, .. ~
and their rel;ative placement with respect to the medicament coating, various bandages have been tested and have been .
found to develop between about 1/2 and 1 volt potential, and between about 2 and about 15 microamperes current, for aluminum foil electrodes. Obviously, various other elec- ;
trode materials will provide differing electrical charac~
teristics.
Yet another embodiment envisioned within the scope of the present invention regards the use of soft,~;
-~ -26- -' , hydrogel rnaterials, such as those disclosed in, for example, United States Patent No. 2,976,576, Re. 27,401, No. 3,220,960, No. 3,503,942, No. 3,639,524, No. 3,699,089, No. 3,721,657 and No. 3,966,847. These materials, which will swell and retain, by hydration, solutions of the desired medicaments, may be employed as carriers therefor in lieu o~ the saturated tissue or sterile gauze materials.
Otherwise, the bandage is identical in all respects to those enumerated above.
While the foregoing embodiments have been predicated basically upon the administration of various medicaments or collagenous dispersions or suspensions from, for example, a bandage substrate, the scope of the present invention is indeed quite broader. For example, it has been learned that very beneficial therapeutic effects may realized upon the application of very minute electrical currents to a mammalian body. In conjunction with this embodiment, as there is no : .
need to deliver an anclllary medicament or the like, the appropriate electric field may be provided by, for example, a bandage substrate such as that described above, and illus_ trated in Figures 1-5, but without the need to provide the coating of collagen or medicament. Consequently, the device becomes exceedingly simple in design and may be comprised of merely an adhesive upon which is borne an appropriate ~ ~:
electrode or electrodes. Indeed, since the fundamental purpose of the adhesive substrate is to serve as a convenient support for the collagen dispersion or medicament, as well - ~.
., .. - .~., . . . :.:~,.:. .: ,;, . , .,, : .,.. . . . , . ~
-~ as the electrodes, even the substrate may be eliminated ~-and the appropriate electro-chemically-active electrodes implanted or otherwise fixed on the mammalian body to be treated.
Regardless, however, of the basic electrode con- `~
figuration employed, it has been ascertained that the ~`
application of currents within the range of from about 0.001 to about 1,000 microamperes, and preferably from about 2.5 to about 500 microamperes, at a volta~e in the range of from about 0.01 to about 3.0 volts, maximi~es the therapeutic efects desired whileconcomitantly diminishing -all of the unwanted side efects attendant the use of conceptually similar methods and articles. These beneficial ~ ~;
therapeutic effects range from the linking of damaged collagen fibrils at the site of the wound, lesion, or the like, to an observable regeneration o~ certain tissues following, for example, surgery. It has also been observed ~ `
that bone ractures may be promoted to enhanced knitting by application o these minute currents. Consequently, the range o benefits derivable by practicing the present invention is indeed exceedingly broad.
`, ,'.
:;: ''.~1~.
'' :::
-~8-:
,.; . :
. : ','
': , ' " " :
3~
I encountered in these situations.
FIG. 1 is a top elevation view of a bandage according to one embodiment of the present invention;
FIG. 2 is a side elevation view of the bandage of FIG. 1;
FIG. 3 is a side elevation view, similar to that of FIG. 2, showing an alternate embodiment of the present invention;
FIG. 4 is a botkom elevation view of a bandage according to yet another embodiment of -the present inven-tion; and ` FIG. S is a slde elevation view of the bandage of FIG. 4.
`:
,::
In order to more fully elucidate upon the objects 15 and advantages of the present invention, the following detailed description will be given in terms of various pre- ~-ferred embodiments and exemplified~with respect thereto.
; ~ The same are intended, however, to be illustrative and in ; no wise limitative.
Furthermore, as used in the context of the present I invention, the term bandage is meant to include all ; varieties of surgical dressings, regardless of physical , configuration, which may be applied over a wound site to : ~, effect treatment therefor. Thus, the present invention t envisions utility extending from the rather small adhesive ~;l bandages to large dressings o~ several squate feet which ~ -8- ~
.`'~s~ ;,.i,.,':
,.. .. . .
may be applied to burn victims.
The first embodlment to be described makes use of the inherent, negative electrlcal potential of an animal body to provide the necessary iontophoretic impetus for electrochemical-linking of collagen fibers contained in a dispersion applied proximate the area to be treated. To achieve these ends, a collagen dispersion is prepared in the same ma~ner as that described in U. S. Patent No.
3,563,228, save for the fact that the collagen concentra-- lO tion in the instant dispersion is greater than the pre-ferred 0.25% to 1% by weight concentration recited therein, e.g., up to about 50% by weight concentration, but most desirably having the consistency of soft table butter.
More specifically, the instant collagen suspension may be ' 15 prepared from bovine deep flexor tendon which has been cleaned and trimmed of fat and other extraneous matter, frozen, and subsequently sliced perpendicular to the longi-tudinal axis of the tendons to a suitable length of about , O.001 mm to 0.5 mm, pref~erably from 0.2 mm to 0.5 mm, albeit ;
such a length is not critical. The collagen ~ibriis may , ~ ~
then be disaggregated by treatment with proteolytic enzyme such as commercial ficin. This treatment may be achieved, for example, by gentle aggitation for approximately 1 hour at 35F in an aqueous solution of ficin. These fibrils ~ ~
25 are then washed with distilled water and treated with ;
aqueous sodium chloride solution of appro~imately 1~ con-centration for about 1 hour in two or three successive treatments. See further said U. S. Patent No. 3,563/228.
, g _ . . .
- , . .:;: .~ . : :, , ~ ,: .. .. ,, : . . ,: ~, : . -- : ,. :
3L.h~ Y~
Having thus been prepared, these fibrils are added to a mixture of equal parts of ethanol and water, optionally containing approximately 0.2% cyanoacetic acid if long-term storage is anticipated; this mixture is then aggitated at a temperature approaching the freezing point thereof and sub-sequently homogenized by a conventional homogenizer.
Optionally, the collagen dispersion may be produced accord- f ing to the teachings of either U. SO Patent No. 3,368,911 -or the process of Battista as described in the ~ournal of 10 Applied Poly~er Science, 11, 41-498 (1967).
Such a dispersion of, for example, 10% collagen concentration, will exhibit a paste-like or syrupy consistency, -~; sometimes similar to that of soft butter. This paste or dis-persio;~ is then enhanced for better conductivity by additions of saline (usually in amounts ranging from between 0.1% to 1.0~ by weight), such as sodium ~hloride or potassium chloride, ` preferably in amounts to render the paste isotonic; that is, ; 0.9~. Metallic salts corresponding to those indigenous to ; the animal body may also be added in similar minute quantities, ~ 20 e.g. in amounts ranging between about 0.01~ and 10~ by weight.
:.. i :
~`I Selection of these salts, specifically to be rich in positive ions, is well within the purview of the skilled artisan.
.', .
~} This paste may then be applied locally over the ~
.", ~
area to be treated. An electrical field will be established I~ 25 between the collagen paste dispersion and the animal body;
`f the paste will exhibit an overall positive char~e while the :.~1 . ` '.:
~ areas surrounding the wound site will exhibit an effective . ,~, j ~
-~ negati~e electrical potential. However, the relative ~f 1 .
. ~
,., ~, :
electrical potential thus established is relatively slight and, thus, the desi~ed electrochemical-linking of the collagen fibrils proceeds rather slowly. Accordinglyl it may be desirable to provide an auxiliary power source, operatin~ in conjunction with the body's inherent electri-cal characteristics, to enhance this action.
Figures 1-3 illustrate another embodiment of the present invention wherein a galva~ic couple is employed to achieve the necessary electrical impetus for electrochemical-linking. Figure l illustrates a bandage, generally design-nated as 10, bearing electrodes ll and 12. The bandage may be selected from numerous commercial varieties well known ~;
; to tnose skilled in the art and is necessary only to pro-vide a suitable substrate upon which the galvanic electrodes may be deposited, as well as a suitable quantity of collagen.
Preferably, the bandage will be comprised of a liquid ~; impervious top layer 13, as shown in Figures 2 and 3, possessing an area 14 wherein a plurality of perforations .. ...
I~ 16 are located~ Characteristics such as flexibility, `, 20 absorbency, etc., will be dictated by individual cases and t .:
~ are well known to the skilled artisan.
"., .
Electrodes ll and 12, which form the galvanic ~;
; couple, may be fabricated from strips of suitable electro-, chemical material, such as metal. The electrodes may be `. ! . .
25 adhered to the upper surface of the bandage in any desired manner, such as adhesive paste. Optionally, these electrodes may be fabricated by dispersing the desired electrochemi-cally-active material in a volatile carrier to form a for-mulation which may then be applied to the bandage. A
quantity of dry electrolyte 18 is disposed intermediate ~ ~-electrodes 11 and 12.
As viewed in Figure 2, a collagen coating, such as that fully described hereinabove, designated as 20, is applied to the opposite side of the bandage and dried.
; Electrode 12 is caused to be maintained in electrical contact with the collagen coating by internally disposed conductive member 19, although electrode 12 may be over-wrapped about the end of the bandage thereby providing this desired electrical contact. Electrode 11 is caused to be electrically insulated from both electrode 12 and the collagen coating 20 and lS overwrapped about the bandage 10 or otherwise caused to make electrical contact with the 15 skin of the animal to be treated at a location apart from ~
the wound area, W. ~;
It is necessary that electrode 12 exhibits a :i positive standard reduction potential with respect to ~` electrode ll to efect the proper polarity therebetween;
that is, current should flow from electrode 12, through the coated collagen layer to the tissue area of interest, and thence to electrode 11, through electrolyte 18 and back to electrode 12 to complete the electrical circuit, as depicted 'l in Figure 2. Thus, if the positive strip 12 is made of a metal which may be strongly attacked by electrolysis, it may , ,.
enter the wound, lesion, etc.. Accordingly, while the electrode 12 may be fabricated from any harmless metal, such as, aluminum, it is preferred that this positive r- - -12-:: - ", ..:: :.,:; :: .;: ,~:
- , , :,,.,-,~", ,:, ::: .
electrode be made from carbon. As regards the composition of electrode 11, any metallic material meeting the fore-going standard reduction potential criterion and one which further exhibits a harmles~ effect on the body may be -, suitably employed.
The bandage according to this embodiment may b-activated by applying a few drops of water to the perforated area 14 which will we-t both the electrolyte 18 and the dried collagen dispersion coating 20. Optionally, the -body's own fluids, such as blood or serum, may be employed to these endsO Once this has been achieved, galvanic action between the two electrodes will assist the inherent ~ ~egat~ve potential o the animal body by providing a current -~ of proper polarity and attendant electric field to aug~ent ~/ 15 that naturally existing~ Accordingly, collagen in the :
hydrated coating will electrochemically-link according to the lines of electric force, E, and the fibrils will form a film or membrane linked with damaged fibrils of the wound to effect an adherent, skin-like protective coating.
` ! : :
~ An alternate embodiment of the topic bandage is depicted in Figure 3 wherein there is now incorporated a :,. . . .
discrete region 22 which is porous in nature. In this embodiment, the material from which the bandage is fabricated ; .
~; is such ~hat the~collagen dispersion described supra may ~` 25 be impregnated therein; for example, foamed polyurethane, , Otherwise, this bandage will operate identical to the ~;
description for the bandage described in Figures 1 and 2.
3~
Further, it will be obvious to the skilled artisan that the bandage depicted in Figures 1-3, and described above, need not employ the saline or metallic salt com-ponents in the collagen dispersion during initial processing thereof. The action of the galvanically generated electric field will, in some cases, be sufficient to supplant the requirement of these constituents by using the body's own fluid components~
Another, and the most preferred embodiment in 10 accordance with the present invention is illustrated in ~ ~;
Figures 4 and 5~ In Figure 4, there is shot~ a bandage generally designated as 40 bearing an area 42 which is a -; film of electrochemically-active material. Borne upon the film 42 is a film of collagen 44. The electrical potential is derived fxom a single active electrode, 42, which i.s in ~; contact with ~he skin of the patient to be treated proximate -~
~' the wound area. The electrode 42 is chosen to ensure ~f~
it possesses negative electrical characteristics with respect i to the collagen film, as shown in Figure 5.
- 20 The materialsl selection for electrode 42 is ;~l restricted primarily upon considerations such as standard reduction potential to ensure the electrode maintains a negative potential with respect to the collagen film; the , , ~
:, ' . ~;
, .
~ -14~
~, /
" : . :,: .. , : .: : :: : - : ~ : :
3i~
'~ `.
propensity for dissolution, to minimize the introduction of the electrode material within the wound area, as well as other considerations well known to the skilled artisan.
Preferred electrode materials are, for example, aluminum, 5 mild silver protein and zinc. However, when zinc is employed, due to its galvanic activity, it is preferable to form electrode 42 as a narrow strip adjacent collagen film 44, in contradistinction to the film shown in Figure 4, wherein the electrode is adjacent the entire periphery of collagen film 44.
~`~ Particularly beneficial results may be realized upon employing a mild silver protein film for electrode 42.
~, ~ild silver protein, a colloidal solution prepared by the :.~ . ,.
interaction of protein and silver oxide and containing about 15 l9 to 23% silver, is a well known bacteriostatic agent. `~
Only a small fraction of the silver is in an ionizable ,::
" state and, thus, mild silver protein is not irritating but, , ln fact, is somewhat demulcent. For a more comprehensive ~, understanding of the uses and~effects of mild silver protein, see Goodman and~Gillman. The Pharmacological Basis of Therapeutics, 3rd Edition, McMillan, 1969.
The mild silver protein membrane may be fabricated ~!
to exhibit either a propensity to disintegrate in moisture or, with good wet strength to preclude such occurrence.
25 Accordingly, the electrode material itself may take an active role in the healing process~
Another of the preferred electrode materials is ; aluminum, a relatively innocuous material with little _ f 5~
:
tendency to dissolve when the bandage is employed. A
bandage similar to that depicted in Figure 5 was fa~ricated for purposes of experimentation. The bandage 40 has an ~;
upper, liquid imper~ious layer 46 and conveniently possesses a pressure sensitive adhesive (not shown) on the obverse side in order to facilitate adherence of the bandage to ~he area for treatment. This test employed a conventional bandage commercially marketed undex the trademark CURAD.
A thin foil of aluminum, for example, 0.002 to 0.003 inches thick, was adhered over a gau2e area 50 of the bandage. A
paste of collagen was prepared in accordance wiih the process described above and deposited over the electrode 42 by means of a doctor blade. The collagen membrane, 44, may ~ r~
?.~
''!^`~ be either supported or unsupported, and may be processed to yield the collagen dispersible or insoluble in water, as desired. Once the bandage was assembled as shown in Figure 5, a drop of saline solutîon was placed upon the collagen ~l~ film. Potentiometric tests were performed upon the bandage at that time and indicated a voltage of 0.5 volts between the electrode and collagen film, and a current of 400 micro-amperes.
Other bandages were fabricated in similar fashion . .
employing electrode materials as set forth in Table I. The voltage and current developed by each of these bandages is - ;
25 likewise set forth in Table I~ ~
,:
, :
-16- ~ ;
.. . .
,.. . ,.-. . ., .; , :: :. ,.. -., . .. : : . . , -:~:
. -.- , . . , . . .. ,....... , ~.. .. .
.3 TABLE I
Electrode MaterialVoltage (V)Current (ua?
Aluminum 0.5 400 Zinc 1.2 200 Tin O.S 50 Titanium 0.15 25 Tantalum 0.1* 2.5 *reverse polarity ` :,:,,:
It has been observed that the collagen dispersion `I 10 borne upon the bandage substrate electrochemically-links ~i in a very short amount of time under the influence of the electrical potential derived from the galvanic source. More-over, the collagen film adherently and tenaciously attaches i to the wound site through both mechanical and chemical link--l 15 ~ages with the exposed, damaged collagen fibrils of the wound.~ Accordlngly, it has further been observed that the handage~substrate~itself may be removed in~a relatively short amount of time, leaving ~ehind this highly adherent, skin-Iike collagen film. Moreover, it has been observed `~
that the collagen film thus applied to the wound site, upon limited dehydration, will contract somewhat and tend to close the wound in a natural manner. These, and other benefits, are realized upon application of materials totally ~` -17-acceptable to the animal undergoing treatment and, accord-ingly, rejection is rare.
Moreover, various modifications may be made to the bandage and/or collagen dispersion of the present inven-tion. For example, mild silver protein may be mixed with ; the collagen dispersion to form a paste of enhanced electro-~; chemical activityO Further, the conductivity of mild silver protein has been found -to be enhanced by a rine spray or il .
~^ mist of ammonia prior to use. Thus, the relative electrical ;~ ~
. , ~ 10 potential between electrodes and~or the collagen f.ilm is ' `; ; ,~ ' : .
capable of a wide range of selection in order that the bandage be adapted ~or tailor-made operation. This is particularly true as the electrochemical-linking phenomenon ~ is a strong function of electrical potential and may be $
15 advanced or retarded based upon materials selection. ~^
It has also been determined that the notable benefits of practicing the presènt invention may be realized -~
: ~ ;
- ~ by impregnating simple tissue paper with the appropriate collagen dlsperslon, with or without additions, rather than ; ;~
``~ 20 ~depositing the~collagen upon a conventional bandage sub-strate. The impregnated paper, whether readily disinte-gratable or possessing wet strength, may then be utilized ~
for treatment, optionally in combination with any of the ~;
galvanic sources described above. In like vein, the collagen dispersion, with~or without additions, may be dried to a film, supported or unsupported, and used without need of any substrate. These~embodiments may prove highly ~eneficial ~``
for treatment of exte~nsive wound areas such as, for example,burns "`
Also, the collagen film may be electrically linked prior to its application to the wound area. Thus, the pre-linked film or membrane may be placed over the area to be treated and one of the foxegoing galvanic sources ; 5 applied to effect linking between the collagen membrane and damaged collagen fibrils of the wound.
~nother embodiment of the present invention per-~ains, broadly, to methods for the iontophoretic administra-~;`` tion of various ionizable or polar medicaments to a mammalian body and a delivery system therefor based upon a bandage such as the one described above~ More specifically, the ~
present invention is particularly adapted for the administra- ;
tion o~ various pxoteinaceous and/or biocompatible metallic medicaments, or derivatives thereof, to a mammalian body ~, 15 from a bandage or bandage-like article under the }nfluence ;~ .~- of an electric field established between the bandage and the body.
~, It is observed that prior art voltaic plasters , ~,;
suffer numerous disadvantages, the most significant being ~` 20 risk of metal poisoning and/or electrode burns to the body being treated due to the construction of the bandage from highly active dissimilar metals as the galvanic electrode materials, and an inability to effectively deliver a wide range of medicinally effective medicaments. Both of these significant drawbacks are overcome by the present invention, by providing an integral electrode on a bandage substrate hav-ing a quantity of medicament also borne thereon. When applied to mammalian body, natural body fluids or applied isotonic fluids will create a voltaic effect whereby the medicament is caused to migrate deeply within a wound, lesion, or the like, to elecit its desired pharmacologic response.
In part, the improvement derived from the present invention is coupled with the recognition that a mammalian body possesses a slight, inherent negative electric charge, ~ particularly at areas proximate the site of a wound, lesion ~ :
.~ or the like. Thus, by appropriate design of a delivery ` 10 device, materials may be employed which advantageously .~ utilize this electrica~ characteristic thereby overcoming the need for disslmilar electrodes to effect the galvanic ::
'i!~ cell while yet providing for the generation of a suitable ~.
-. electric field fox :the iontophoretic impetus. The improve-ment in the iontophoretic administration of medicaments in accordance with the present invention lies also, in part, in administering a broad range of ionizabIe or polar compounds ~ :
responsive to the applied el.ectric field. ~`
. : ~ : ;
;~~ : Whlle numerous anionic, cationic, and polar medi-20~ caments, including certain amphoteric medicaments, are envisioned within the scope of the present invention, the preferred are proteinaceous medicaments, eithex undenatured : or denatured. Thus, these preferred medicaments include -,~"
. the protein component of mild or strong silver protein, ~.
: 25 alginates, and the like. Additionally, various effective metallic salts may be employed in the iontophoretic admini- :
: stration method according to the present invention in con~
junction with the;protein or derivative thereof. It has : "
_~o_ :
, :
:
been determined that the proteinaceous medicament may be employed alone when the protein component is not denatured.
;; When, however, that protein component is denatured, it is particularly beneficial to employ a metallic salt, most ;~
preferably a silver salt. However, other medicinally-~- effective equivalent metallic salts might be utilized. ~-~; Likewise, other medicaments including, particularly, Dexamethasone Sodium Phosphate, Methylprednisolone Sodium ~ Succinate, Flurandrenolide, and Amphotericin, are preferred ;~ 10 compounds for use in conjunction with the present invention.
These compounds may be employed individually or in admixture, -~
with or without the additional presence of metallic salts, or denatured or undenatured mild silver proteins. Moreover, ., other various steroids, antibiotics, and antifungal com-pou~ds, or the like, may also be employed, together or separ-ately as might be desired. Further medicinally-effective ..
compounds and preparations may be selected from -s~ecific ;
pharmacological efects, such selection being within the scope of those skilled in the art.
The most preferred proteinaceous medicament is the antiseptlcally-effective mild silver protein, which is a colloid of silver with protein, containing on the order o about 10 to 25~ silver. This material is readily available, commercially; and is described in "The Merck Index", Merck 25 & Co., Inc., 5th Edition, 1940, page 458. However, other -anti-infectious, analgesic, bacteriostatic, and like proteinaceous compounds may be employed to this end.
In electrically-cooperative relationship with the _ -21-3~
medicament is an electrode, which may assume any of a number of physical configurations. Most preferably is a metallic foil, although any electrochemically-active material may be utilized and may be deposited in the form of a liquid j`
such as, for example, dispersion, and subsequently dried.
The electrode material should be selected from those known to be compatible with the mammalian body for the obvious -~
reasons including toxicity, irritation, etc. As will become more apparent hereinbelow, a salient distinction between the bandage of the present invention and those of the prior ,. }
-~ art is the absence of a galvanic couple of active metallic j ~ , `1 components on the bandage su~strate to which has been attributed the significant problems of electrode burns and/
~,'JI~or metal poisoning indigenous to the latter. That is, the instant-bandage employs but a singular electrochemically~
aetive material for the eleetrode, regardless of the physical ~ `
, ,~
state or configuration thereof, i.e.~ a bandage such as illus~
`~ trated in Figures 4 and 5. Of course, for the iontophoretic administration of certain of;the medicaments within the scope .. . ~
of the present invention, particularly those not heretofore , : . j iontophoretically administered (espeeially proteinaceous and ~ ;
protein/metallic medicaments), a conventional galvanic ;~
couple might be employed, e.g., a bandage such as illustrated in Figures 1-3. However, in seleetion of the appropriate materials for the couple, the skilled artisan will readily ~`
appreciate that less active metallie eomponents than utilized in prior art devices may well be ehosen due to the augmentive nature of the instant bandage respecting the ~- - ~22-.. .
33~
inherent electrical characteristics of the mammalian body to which the bandage will be applied.
; The most preferred electrode is a foil of aluminum metal. Other electrode materials include, for example, 5 copper, zinc, tin, and titanium, each of which will provide ~
an effective positive charge with respect to the mammalian ~;
- body. Should the medicament utilized require a net negative charge to provide the desired iontophoretic impetus of ~` proper polarity, such materials as tantalum might be utilized 0 Regardless of the electrode material or configura-tion thereof, it is essential that the electrode be in electrically-cooperative relationship with the medicament to be iontophoretically administered. As a consequence when the bandage is activated by electrolytic fluids such as, for example, body fluids or administered isotonic saline, voltaic interaction wlll establish an electric field between the electrode and underlying wound site and generate a corresponding electric current, whereby the ~;
medicament is caused to migrate deeply within the wound in ~
;!~ : ~ ,. . ...
20~ response thereto.
The present invention envisions utility extending -from small adhesive bandages to large dressing of several square feet which may be applied to, for example, burn victims. Exemplary of a particularly suitable bandage is that of Figure 4, denoted generally as 40, which is com~
:~ .
prised of, e.g., a 6" x 2" substrate 46, having a medial ~;
portion and terminal portions. The medial portion has adhered thereto a foil of, for example, aluminum metal, _ _~3--`' ~' 3~
denoted as 42. The foil optimally comprises approximately ~ ~
one half of the total surface area of the bandage substrate; ~; -~' however, these dimensions are not critical provided the electrode material has sufficient surface area to provide ; 5 the required iontophoretic effective electric current.
The central portion of the electrode 42 has I~ coated thereon, or adhered thereto, a quantity of the -~
;~ desired medicament 44. Preferably, the medicament is applied as a paste or liquid to some absorbent material ~
~, 10 such as tissue paper or sterile cloth or gauze. The medica~ ;-ment is allowed to dry and the porous carrier adhered to , the foil electrode.
`1 An optional embodiment employs a commercially- -available surgical bandage, such as those marketed under the trademark "CURAD". As opposed to the bandage of Figure 4, which may be made in relatively large dimensions, and ~
wherein the terminal portions may or may not be coated with ~`;
an adhesive substance, this altexnate embodiment is designed ~ `
.
~ ~for application to rather small cutst abrasions or the like.
:.
The bandage is comprised of a plastic or polymeric substrate having a medial portion and adhesively coated end portions with an absorbent gauze adhered to the substrate in the -medial portion. Two foil electrodes, such as 42' shown in Figure 4, are also borne upon the substrate and are caused 25 to partially~overlap the medial gauze area. The desired ~ -~
medicament may be applied to the gauze pad and allowed to dry.
~` A bandage in accordance with this latter embodiment '. ~
_ -24- ;
- `'- :.
was prepared in order to ascertain the effectiveness of the iontophoretic administration of mild silver protein to a human body. The bandage employed is approxlmately 7.5 cm long and 2.5 cm wide. The gauze pad accounts for approxi-5 mately 30% of the total surface area of the bandage and iscoated with a solution of mild silver protein (USP) made isotonic with 0.9% sodium chloride. After the medicament has dried, two rectangular strips of aluminum oil having dimensions of about 2.5 cm x 2.0 cm are adhered to the bandage substrate, partially overlapping the coated gauze area such that approximately 15~ of each aluminum foil strip is in direct contact with the coated gauze pad.
This bandage was placed on a human body over a minor wound. A drop o isotonic saline was administered to ~`~
lS the coated gauze pad in order to establish voltaic action between the aluminum foil electrodes and the body. The electric potential was measured to be about 3/4 of a volt, and the current generated about 10 microamperes. In response to the electric field thus generated, the silver protein .
medicament~migrated deeply within the wound at a rate much greater than wére the electric field absent.
A similar bandage was prepared employing as a ;substrate, a commercially-available bandage, marketed under the name "Air-Vent Tape Clear", by Johnson & Johnson.
;25 This bandage, measuring about 9.0 cm x 2.6 cm, was placed with the adhesive side-up, upon which was adhered, in the -~
central portion thereof, a foil of aluminum me~al measuring about 4.5 cm x ~2.0~cm x 0.0254 mm. The adheslve of the ,:
3~ r bandage provided suficient area for firm attachment of the foil thereto, leaving a sm~ll peripheral strip of adhesiye exposed along the longitudinal edges of the foil due to its narrower transverse dimension relative to that of the bandage.
Sterile tissue paper, measuring 2.4 cm x 2.4 cm, was soaked in a 10% solution of mild silver protein made .
isotonir with 0.9% sodium chloride. The tissue was removed ;~
: :
from this solution and permitted to dry. Subsequently, the impregnated tissue was placed over the aluminum foil, the exposed adhesive from the bandage providing means for firm ;~
`~ attachment.
This bandage was applied over a cut on a human ~' body, perspiration and wound serum providing the re~uisite 15 poly-electrolyte. The voltage of the resultant electric ~;
field was measured at about l volt; the current varied between 5 and 15 microamperes as the iontophoretic process ~;;
proceeded to carry the medicament deeply within the wound.
Depending upon the configuration of the electrodes, .. ~
and their rel;ative placement with respect to the medicament coating, various bandages have been tested and have been .
found to develop between about 1/2 and 1 volt potential, and between about 2 and about 15 microamperes current, for aluminum foil electrodes. Obviously, various other elec- ;
trode materials will provide differing electrical charac~
teristics.
Yet another embodiment envisioned within the scope of the present invention regards the use of soft,~;
-~ -26- -' , hydrogel rnaterials, such as those disclosed in, for example, United States Patent No. 2,976,576, Re. 27,401, No. 3,220,960, No. 3,503,942, No. 3,639,524, No. 3,699,089, No. 3,721,657 and No. 3,966,847. These materials, which will swell and retain, by hydration, solutions of the desired medicaments, may be employed as carriers therefor in lieu o~ the saturated tissue or sterile gauze materials.
Otherwise, the bandage is identical in all respects to those enumerated above.
While the foregoing embodiments have been predicated basically upon the administration of various medicaments or collagenous dispersions or suspensions from, for example, a bandage substrate, the scope of the present invention is indeed quite broader. For example, it has been learned that very beneficial therapeutic effects may realized upon the application of very minute electrical currents to a mammalian body. In conjunction with this embodiment, as there is no : .
need to deliver an anclllary medicament or the like, the appropriate electric field may be provided by, for example, a bandage substrate such as that described above, and illus_ trated in Figures 1-5, but without the need to provide the coating of collagen or medicament. Consequently, the device becomes exceedingly simple in design and may be comprised of merely an adhesive upon which is borne an appropriate ~ ~:
electrode or electrodes. Indeed, since the fundamental purpose of the adhesive substrate is to serve as a convenient support for the collagen dispersion or medicament, as well - ~.
., .. - .~., . . . :.:~,.:. .: ,;, . , .,, : .,.. . . . , . ~
-~ as the electrodes, even the substrate may be eliminated ~-and the appropriate electro-chemically-active electrodes implanted or otherwise fixed on the mammalian body to be treated.
Regardless, however, of the basic electrode con- `~
figuration employed, it has been ascertained that the ~`
application of currents within the range of from about 0.001 to about 1,000 microamperes, and preferably from about 2.5 to about 500 microamperes, at a volta~e in the range of from about 0.01 to about 3.0 volts, maximi~es the therapeutic efects desired whileconcomitantly diminishing -all of the unwanted side efects attendant the use of conceptually similar methods and articles. These beneficial ~ ~;
therapeutic effects range from the linking of damaged collagen fibrils at the site of the wound, lesion, or the like, to an observable regeneration o~ certain tissues following, for example, surgery. It has also been observed ~ `
that bone ractures may be promoted to enhanced knitting by application o these minute currents. Consequently, the range o benefits derivable by practicing the present invention is indeed exceedingly broad.
`, ,'.
:;: ''.~1~.
'' :::
-~8-:
,.; . :
. : ','
Claims (65)
1. A bandage adapted for application to a mammalian body having a wound, lesion or the like, said bandage comprising:
(a) a bandage substrate adapted for application to said body;
(b) a single metallic electrode, at least a part of said electrode being in direct contact with the body; and (c) collagen and/or an ionizable or polar medi-cament in electrically co-operative relation-ship with said electrode;
said bandage being capable in use of forming a galvanic couple between said single electrode and said body when said bandage is applied over said wound, lesion or the like, and producing, without use of an external power source, a local current effective for iontophoresis or for applying a small electric charge to said body.
(a) a bandage substrate adapted for application to said body;
(b) a single metallic electrode, at least a part of said electrode being in direct contact with the body; and (c) collagen and/or an ionizable or polar medi-cament in electrically co-operative relation-ship with said electrode;
said bandage being capable in use of forming a galvanic couple between said single electrode and said body when said bandage is applied over said wound, lesion or the like, and producing, without use of an external power source, a local current effective for iontophoresis or for applying a small electric charge to said body.
2. A bandage as claimed in Claim 1 wherein the electrode is aluminum.
3. A bandage as claimed in Claim 1 wherein the electrode is aluminum foil.
4. A bandage as claimed in Claim 1 wherein collagen is in electrically co-operative relation-ship with said electrode.
5. A bandage as claimed in claim 1 wherein an ionizable or polar medicament is in electrically co-operative relationship with said electrode.
6. A bandage as claimed in Claim 5 wherein collagen and an ionizable or polar medicament are in electrically co-operative relationship with said electrode.
7. A bandage as claimed in Claim 4, 5 or 6 wherein the electrode is aluminum.
8. A bandage as claimed in Claim 4, 5 or 6 wherein the electrode is aluminum foil.
9. A bandage as claimed in Claim 5 wherein said medicament is borne on the substrate.
10. A bandage as claimed in Claim 9 wherein the medicament is absorbed within a carrier, said carrier comprising sterile paper, sterile cloth or hydrogel polymer, said carrier being adhered to said bandage.
11. A bandage as claimed in Claim 9 wherein the medicament comprises a proteinaceous medicament, said proteinaceous medicament comprising an undenatured or a denatured protein.
12. A bandage as claimed in Claim 11 wherein the proteinaceous medicament comprises a denatured protein further including a biocompatible metal.
13. A bandage as claimed in Claim 12 wherein the biocompatible metal is silver.
14. A bandage as claimed in Claim 9 wherein the medicament is mild silver protein.
15. A bandage as claimed in Claim 14 wherein the electrode is aluminum foil.
16. A bandage as claimed in Claim 14 wherein the electrode is aluminum foil, further comprising a second electrode of aluminum foil.
17. A bandage as claimed in Claim 10 wherein the medicament comprises a proteinaceous medicament, said proteinaceous medicament comprising an undenatured or a denatured protein.
18. A bandage as claimed in Claim 17 wherein the proteinaceous medicament comprises a denatured protein further including a biocompatible metal.
19. A bandage as claimed in Claim 18 wherein the biocompatible metal is silver.
20. A bandage as claimed in Claim 10 wherein the medicament is mild silver protein.
21. A bandage as claimed in Claim 20 wherein the electrode is aluminum foil.
22. A bandage as claimed in Claim 20 wherein the electrode is aluminum foil, further comprising a second electrode of aluminum foil.
23. A bandage as claimed in Claim 5 wherein said substrate defines a medial portion bounded by terminal portions, said electrode being borne upon said substrate within said medial portion and supporting a discrete quantity of said medicament within its periph-eral dimensions, said electrode presenting sufficient surface area for direct contact with said body to establish an iontophoretically-effective electric current between said medicament and said body to cause migration of said medicament deeply within said wound, lesion or the like thereon.
24. A bandage as claimed in Claim 23 wherein the electrode is aluminum foil.
25. A bandage as claimed in Claim 24 wherein said medicament is absorbed within a carrier selected from the group consisting of sterile paper, sterile cloth, and hydrogel polymers, said carrier being adhered to said bandage.
26. A bandage as claimed in Claim 24 wherein said medicament is a proteinaceous medicament comprised of an undenatured or a denatured protein.
27. A bandage as claimed in Claim 26 wherein said proteinaceous medicament comprises a denatured protein and further includes a biocompatible metal.
28. A bandage as claimed in Claim 27 wherein the metal is silver.
29. A bandage as claimed in Claim 27 wherein the proteinaceous medicament is mild silver protein.
30. A bandage as claimed in Claim 5 wherein said substrate defines a medial portion bounded by terminal portions, said medicament borne upon said substrate being within said medial portion, said electrode being confined to at least one of said terminal portions and partially overlapping said medial portion in electrically-cooperative relation-ship with said medicament.
31. A bandage as claimed in Claim 30 wherein the electrode is aluminum foil.
32. A bandage as claimed in Claim 31 wherein said medicament is absorbed within a carrier selected from the group consisting of sterile paper, sterile cloth, and hydrogel polymers, said carrier being adhered to said bandage.
33. A bandage as claimed in Claim 31 wherein said medicament is a proteinaceous medicament comprised of an undenatured or a denatured protein.
34. A bandage as claimed in Claim 33 wherein said proteinaceous medicament comprises a denatured protein and further includes a biocompatible metal.
35. A bandage as claimed in Claim 34 wherein the metal is silver.
36. A bandage as claimed in Claim 34 wherein the proteinaceous medicament is mild silver protein.
37. A bandage as claimed in Claim 1 further including an electrochemically-effective quantity of an electrolyte.
38. A bandage as claimed in Claim 37 wherein the electrolyte is sodium chloride, potassium chloride or a mixture thereof.
39. A bandage as claimed in Claim 1, 2 or 3 comprising a film-forming quantity of collagen fibrils so as to obtain in use an adherent skin-like protective membrane of collagen fibrils electrochemically-linked to the exposed collagen fibrils of the wound, lesion or the like.
40. A bandage as claimed in Claim 37 or 38 comprising a film-forming quantity of collagen fibrils so as to obtain in use an adherent skin-like protective membrane of the collagen fibrils electrochemically-linked to the exposed collagen fibrils of the wound, lesion or the like.
41. A bandage as claimed in Claim 37 comprising a film-forming quantity of collagen fibrils, said fibrils being present in the form of a dispersion thereof the consistency of paste, supported by the substrate and containing said electrolyte, so as to obtain in use an adherent skin-like protective membrane of the collagen fibrils electrochemically-linked to the exposed collagen fibrils of the wound, lesion or the like.
42. A bandage as claimed in Claim 38 comprising a film-forming quantity of collagen fibrils, said fibrils being present in the form of a dispersion thereof the consistency of paste, supported by the substrate and containing said electrolyte, so as to obtain in use an adherent skin-like protective membrane of the collagen fibrils electrochemically-linked to the exposed collagen fibrils of the wound, lesion or the like.
43. A bandage as claimed in Claim 41 or 42 wherein the collagen dispersion is coated on the substrate.
44. A bandage as claimed in Claim 41 or 42 wherein the collagen dispersion is impregnated in the substrate.
45. A bandage as claimed in Claim 41 or 42 wherein the collagen dispersion is dried.
46. A bandage as claimed in Claim 1, 2 or 3 comprising a film-forming quantity of collagen fibrils so as to obtain in use an adherent skin-like protective membrane of collagen fibrils electrochemically-linked to the exposed collagen fibrils of the wound, lesion or the like, said bandage further comprising a second metallic electrode.
47. A bandage as claimed in Claim 1 wherein the metallic electrode is applied to said substrate in the form of a dispersion thereof with a volatile carrier.
48. A bandage as claimed in Claim 1, 4 or 5 wherein the electrode is aluminum, zinc, titanium, tin or mild silver protein.
49. A bandage as claimed in Claim 6 wherein the electrode is aluminum, zinc, titanium, tin or mild silver protein.
50. A bandage as claimed in Claim 37 wherein the electrode is aluminum, zinc, titanium, tin or mild silver protein.
51. A bandage as claimed in Claim 1 comprising a film-forming quantity of collagen fibrils, the metallic electrode being in the form of a metallic film upon which the collagen fibrils are borne in electrically cooperative relationship such that, in use, upon introduction of fluid to the bandage, a galvanic current is generated whereby the collagen fibrils electrochemically link to the exposed collagen fibrils of the wound, lesion or the like to form an adherent skin-like protective membrane.
52. A bandage as claimed in Claim 51 further including a functionally-effective amount of mild silver protein mixed with said collagen fibrils.
53. A bandage as claimed in Claim 51 comprising a medicament.
54. A bandage as claimed in Claim 53 wherein said medicament is absorbed within a carrier, said carrier being sterile paper, sterile cloth or hydrogel polymer, said carrier being adhered to said bandage.
55. A bandage as claimed in Claim 53 wherein said medicament is a proteinaceous medicament comprised of an undenatured or a denatured protein.
56. A bandage as claimed in Claim 55 wherein said proteinaceous medicament further comprises a biocompatible metal.
57. A bandage as claimed in Claim 56 wherein the biocompatible metal is silver.
58. A bandage as claimed in Claim 55 wherein the medicament is mild silver protein.
59. A bandage as claimed in Claim 51, 52 or 53 wherein the metallic electrode is aluminum metal.
60. A bandage as claimed in Claim 54, 55 or 56 wherein the metallic electrode is aluminum metal.
61. A bandage as claimed in Claim 57 or 58 wherein the metallic electrode is aluminum metal.
62. A bandage as claimed in Claim 58 wherein the metallic electrode is aluminum metal and wherein said aluminum metal is applied as a foil or a paint.
63. A bandage as claimed in Claim 41 or 42 wherein said collagen fibrils are from 0.001 to 0.5 mm in length.
64. A bandage as claimed in Claim 41 or 42 wherein said electrolyte is present in a concentration of from .1% to 1.0% by weight.
65. A bandage as claimed in Claim 41 or 42 further comprising a metallic salt in a concentration of from 0.1% to 10.0% by weight.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US75877477A | 1977-01-12 | 1977-01-12 | |
| US758,774 | 1985-07-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1113396A true CA1113396A (en) | 1981-12-01 |
Family
ID=25053063
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA282,068A Expired CA1113396A (en) | 1977-01-12 | 1977-07-05 | Iontophoretic medicinal treatments of mammalian bodies and articles therefor |
Country Status (7)
| Country | Link |
|---|---|
| JP (1) | JPS5389295A (en) |
| AT (1) | AT367300B (en) |
| BE (1) | BE856603A (en) |
| CA (1) | CA1113396A (en) |
| DE (1) | DE2730990A1 (en) |
| FR (1) | FR2377204A1 (en) |
| NL (1) | NL7707627A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8118857B2 (en) * | 2007-11-29 | 2012-02-21 | Boston Scientific Corporation | Medical articles that stimulate endothelial cell migration |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60203270A (en) * | 1984-03-27 | 1985-10-14 | 鈴木 茂樹 | Subcataneous drug administration method and apparatus |
| AU4198785A (en) * | 1984-05-07 | 1985-11-14 | Lloyd A. Ferreira | Conductive material and biomedical electrode |
| DE4114677A1 (en) * | 1990-10-10 | 1992-02-27 | Mario Bergner | APPLICATION ARRANGEMENT OF DIFFERENT ELECTRICALLY CONNECTED METALS ON THE HUMAN BODY TO A BIOELECTRIC SYSTEM IN THE MEANING OF THE ELECTROCHEMICAL VOLTAGE RANGE WITH VOLTAGE INCREASING WITH POSSIBLE USE OF COMMERCIAL ECG FLASHER ELEMENTS |
| DE4203898C2 (en) * | 1991-05-06 | 1993-11-25 | Mario Bergner | Patch assembly for galvanic treatment |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1570570A (en) * | 1968-03-28 | 1969-06-13 | ||
| FR2263792A1 (en) * | 1974-03-12 | 1975-10-10 | Bondivenne Jean | Ionotherapy current generator - comprises thin flexible bag giving percutaneous medicament penetration |
-
1977
- 1977-07-05 CA CA282,068A patent/CA1113396A/en not_active Expired
- 1977-07-08 DE DE19772730990 patent/DE2730990A1/en not_active Withdrawn
- 1977-07-08 NL NL7707627A patent/NL7707627A/en not_active Application Discontinuation
- 1977-07-08 BE BE2056071A patent/BE856603A/en not_active IP Right Cessation
- 1977-07-08 FR FR7721165A patent/FR2377204A1/en active Granted
- 1977-07-11 JP JP8207577A patent/JPS5389295A/en active Pending
- 1977-07-11 AT AT0496977A patent/AT367300B/en not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8118857B2 (en) * | 2007-11-29 | 2012-02-21 | Boston Scientific Corporation | Medical articles that stimulate endothelial cell migration |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5389295A (en) | 1978-08-05 |
| ATA496977A (en) | 1981-11-15 |
| DE2730990A1 (en) | 1978-07-13 |
| AT367300B (en) | 1982-06-25 |
| NL7707627A (en) | 1978-07-14 |
| FR2377204B1 (en) | 1981-05-08 |
| BE856603A (en) | 1977-10-31 |
| FR2377204A1 (en) | 1978-08-11 |
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