U.S. patent number 3,731,683 [Application Number 05/150,085] was granted by the patent office on 1973-05-08 for bandage for the controlled metering of topical drugs to the skin.
This patent grant is currently assigned to Alza Corporation. Invention is credited to Alejandro Zaffaroni.
United States Patent |
3,731,683 |
Zaffaroni |
* May 8, 1973 |
**Please see images for:
( Certificate of Correction ) ** |
BANDAGE FOR THE CONTROLLED METERING OF TOPICAL DRUGS TO THE
SKIN
Abstract
Bandage for the topical administration of controlled
therapeutically effective quantities of topically active drugs has
a backing member, a pressure-sensitive adhesive, and a reservoir
layer containing a topically active drug confined within a wall
member. The wall member is formed from drug release rate
controlling material to continuously meter the flow of a
therapeutically effective amount of the drug through the wall to
the skin at a controlled and predetermined rate over a period of
time.
Inventors: |
Zaffaroni; Alejandro (Atherton,
CA) |
Assignee: |
Alza Corporation (N/A)
|
[*] Notice: |
The portion of the term of this patent
subsequent to August 10, 1988 has been disclaimed. |
Family
ID: |
22533069 |
Appl.
No.: |
05/150,085 |
Filed: |
June 4, 1971 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
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136981 |
Apr 23, 1971 |
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Current U.S.
Class: |
424/434; 604/304;
424/448; 424/449 |
Current CPC
Class: |
A61K
9/7084 (20130101); A61K 9/7061 (20130101); A61K
9/7069 (20130101); A61K 9/7092 (20130101) |
Current International
Class: |
A61K
9/70 (20060101); A61f 007/02 () |
Field of
Search: |
;128/260,268,156,296
;424/22,28 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Rosenbaum; Charles F.
Parent Case Text
RELATED APPLICATIONS
This application is a continuation-in-part of Ser. No. 136,981,
filed Apr. 23, 1971, (Docket No. I.R. 165A-CIP; D-110), entitled
"Therapeutic Adhesive Tape," of Alejandro Zaffaroni.
Claims
What is claimed is:
1. A medical bandage for the continuous administration to the skin
or mucosa of controlled quantities of topically active drugs over a
prolonged period of time, said bandage comprising a laminate of (1)
a backing member defining one face surface of the bandage; (2) a
pressure-sensitive adhesive adapted for contact with the skin or
mucosa, the external surface of said pressure-sensitive adhesive
defining the other face surface of the bandage and disposed between
the face surfaces defined by (1) and (2); (3) at least one
reservoir comprised of a topically active drug formulation confined
within a wall member, said wall member being formed from drug
release rate controlling material to continuously meter the flow of
drug from the said reservoir to the skin or mucosa at a controlled
and predetermined rate over a prolonged period of time.
2. The medical bandage of claim 1, wherein said bandage comprises a
laminate of: (1) a backing member; bearing (2) a pressure-sensitive
adhesive on one surface thereof adapted for contact with the skin,
said pressure-sensitive adhesive having distributed therethrough;
(3) a plurality of discrete microcapsules, each of which
microcapsules comprises a topically active drug formulation
confined within a wall member, said wall member being formed from
drug release rate controlling material to continuously meter the
flow of a therapeutically effective amount of the drug in the skin
through the wall of said microcapsules at a controlled and
predetermined rate over a period of time.
3. The bandage as defined by claim 2, wherein each of said
microcapsules (3) is comprised of topically active drug formulation
microencapsulated with the drug release rate controlling
material.
4. The bandage as defined by claim 2, wherein each of said
microcapsules (3) is comprised of a matrix of the drug release rate
controlling wall material, said matrix having the topically active
drug formulation distributed therethrough.
5. The bandage as defined by claim 2, wherein the drug formulation
includes a pharmacologically acceptable solvent.
6. The medical bandage of claim 1, wherein said bandage comprises a
laminate of: (1) a backing member; bearing (2) a discrete, middle
reservoir layer, which reservoir layer is comprised of topically
active drug formulation confined within a wall member, said wall
member being formed from drug release rate controlling material to
continuously meter the flow of a therapeutically effective amount
of the drug to the skin through the wall at a controlled and
predetermined rate over a period of time; and (3) a
pressure-sensitive adhesive adapted for contact with the skin and
carried by the reservoir remote from the backing member.
7. The bandage as defined by claim 6, wherein the reservoir layer
(2) is comprised of a walled container having an interior chamber
containing the topically active drug formulation.
8. The bandage as defined by claim 6, wherein the reservoir layer
(2) is comprised of a matrix of the drug release rate controlling
wall material, said matrix having the topically active drug
formulation distributed therethrough.
9. The bandage as defined by claim 6, wherein the drug formulation
includes a pharmacologically acceptable solvent.
10. The bandage as defined by claim 6, further comprising a
solubility membrane (4) interposed between said reservoir layer (2)
and said surface of pressure-sensitive adhesive (3). 11. The
bandage as defined by claim
2, wherein the rate release controlling material is silicone
rubber. 12. The bandage as defined by claim 6, wherein the rate
release
controlling material is silicone rubber. 13. The bandage as defined
by claim 2, wherein the rate release controlling material is a
hydrophilic
polymer of an ester of an olefinic acid. 14. The bandage as defined
by claim 6, wherein the rate release controlling material is a
hydrophilic polymer of an ester of an olefinic acid.
Description
BACKGROUND OF THE INVENTION
This invention relates to a device for the administration of drugs
and more particularly to a medical bandage for the predetermined
controlled metering of the flow of topically active drugs to the
skin over a period of time. Topically active drugs, as that term is
used in this specification and the appended claims, are agents
which primarily cause a pharmacological or physiological response
at or near the site of their application. They are to be
distinguished from systemically active drugs which are transported
from their site of application by the recipient's circulatory
system or lymphatic system, to cause a pharmacologic or physiologic
response at a remote site in the body.
A large number of locally acting drugs are available to treat skin
disorders or other conditions which manifest themselves in a manner
such that they are susceptible to treatment via the skin. These
drugs can be broadly classified as astringents, irritants,
sclerosing agents, caustics, melanizing and demelanizing agents,
keratolytics, mucolytics, antibacterials, anti-fungals,
anti-inflammatories, antiporasitics, antiperspirants and
deodorants, and the like. These drugs are conventionally topically
administered to the skin with the active agent carried in the form
of ointments, creams, salves, liniments, powders, dressings, and
the like. The popularity of these types of formulations resides in
the fact that it is quite easy to topically apply the agent to the
skin in this manner. In most cases, however, it is not possible to
determine how much of the preparation has been taken up or
effectively administered to the skin since only non-uniform levels
of the agent are available. A further undesirable feature is the
unsightliness of these formulations which often discourage patients
from using them during their waking hours of the day when they are
most likely to be seen by others. Further, the preparations are
subject to rub off onto clothing, thus causing much inconvenience
and annoyance to the user.
In order to obviate some of these undesirable effects, it has been
proposed to provide medicinal bandages wherein the absorbent
portion to be applied to the area to be treated is further provided
with drug material adhered thereto. The advantage of a bandage
construction of this type, of course, resides in the elimination of
the intermediate step of applying the drug. A further advantage is
realized by the elimination of the possibility that the drug which
is often in a liquid formulation will be lost by run-off or
leakage. A significant disadvantage, however, also exists with
these prior art devices for the administration of topically active
drugs in that the amount of medication applied to the affected
areas cannot be accurately controlled, nor is there any assurance
that sufficient medication will be available for the duration of
periods that it is required.
It has also been proposed to admix certain topical drugs in the
adhesive materials of bandages to treat various skin conditions
with improved convenience; see for example British Pat. No.
1,216,908. Further, it is known that medicaments can be
incorporated into certain types of crushable microcapsules which
are then incorporated in bandages; see for example Goldfarb U.S.
Pat. No. 3,464,413. The microcapsules, however, merely function as
drug carriers releasing the drug by rupture of the microcapsules.
Therefore, these bandages are not suitable for continuously
controlling the dosage of the drug administered, which is a most
desirable objective of drug therapy.
SUMMARY OF THE INVENTION
Accordingly, an object of this invention is to provide a bandage
for the improved continuous administration of predetermined
controlled quantities of topically active drugs to the skin over a
period of time.
In accomplishing these objects, this invention in its broadest
aspects resides in a medicated bandage for the continuous
administration of controlled quantities of topically active drugs
to the skin of a patient by direct application to the affected skin
area. The bandage is comprised of a laminate of: (1) a backing
member defining one face surface of the bandage; (2) a
pressure-sensitive adhesive adapted for contact with the skin or
mucosa, the external surface of said pressure-sensitive adhesive
defining the other face surface of the bandage and disposed between
the face surfaces defined by (1) and (2); (3) at least one
reservoir comprised of a topically active drug formulation confined
within a wall member, said wall member being formed from drug
release rate controlling material to continuously meter the flow of
drug from the said reservoir to the skin or mucosa at a controlled
and predetermined rate over a prolonged period of time.
The term"reservoir" as used herein refers both to microcapsules as
well as distinct reservoir compartments or matrix layers.
An embodiment of the invention described above resides in a bandage
comprised of a laminate of: (1) a backing member; bearing (2) a
discrete middle reservoir layer containing a topically active
therapeutic agent confined within a wall member, said wall member
being formed from drug release rate controlling material permeable
to the passage of agent, to continuously meter the flow of a
therapeutically effective amount of the agent to the skin from the
reservoir at a controlled and predetermined rate over a period of
time; and (3) a pressure-sensitive adhesive surface adapted for
contact with the skin and positioned on one wall of the reservoir
remote from the backing member.
Another aspect of this invention resides in a bandage as described
immediately above including a solubility membrane interposed
between the wall of the reservoir and the pressure-sensitive
adhesive layer.
Still, another embodiment of this invention resides in a medicated
adhesive bandage comprising a laminate of: (1) a backing member;
bearing (2) a pressure-sensitive adhesive on one surface thereof
adapted for contact with the skin, said pressure-sensitive adhesive
having distributed therethrough, (3) a plurality of discrete
microcapsules, each of which microcapsules comprise a topically
active therapeutic agent confined within a wall member, the wall
member being formed from drug release rate controlling material, to
continuously meter the flow of a therapeutically effective amount
of the agent to the skin from the microcapsules at a controlled and
predetermined rate over a period of time.
Other objects, features and advantages of the invention will become
more apparent from the following description when taken in
conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
In the drawings:
FIG. 1 is a perspective view of the medical adhesive bandage of the
invention wherein the topically active agent is microencapsulated
with a material permeable to the passage of those agents and the
microcapsules are uniformly distributed throughout the
pressure-sensitive adhesive coating;
FIG. 2 is a cross-sectional view of the bandage of the invention
shown in FIG. 1;
FIG. 3 is a cross-sectional view of another embodiment of the
invention wherein the topically active agent is uniformly
distributed throughout a matrix of material permeable to the
passage of those agents and the material is laminated to a backing
member. The matrix material which acts as a reservoir for the agent
bears a coating of the pressure-sensitive adhesive thereon;
FIG. 4 is a cross-sectional view of still another embodiment of the
invention wherein the adhesive bandage of the invention is
comprised of a backing member having a reservoir on one surface
thereof of topically active agent uniformly distributed throughout
a matrix of material permeable to passage of agent, and on the
surface of the reservoir remote from the backing member bearing a
pressure-sensitive adhesive coating. A solubility membrane is
interposed between the reservoir layer and the pressure-sensitive
adhesive coating;
FIG. 5 is a cross-sectional view of another embodiment of the
invention wherein the reservoir laminated to the backing member is
a hollow container permeable to passage of agent and having the
agent confined within the interior chamber thereof.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with this invention there is provided a medicated
bandage containing a topically active drug therein for the
predetermined controlled metering of the flow of topically active
drugs to the skin over a period of time.
FIG. 1 illustrates an adhesive tape 10 of the invention including a
backing member 11 bearing a pressure-sensitive adhesive coating 12
on one surface thereof. Adhesive coating 12 has uniformly
distributed therethrough microcapsules 13 of topically active agent
encapsulated with a material permeable to passage of the drug.
Materials used to encapsulate the drug and form the microcapsules
to be distributed throughout the adhesive must be permeable to the
drug to permit passage of the drug, as by diffusion, through the
walls of the microcapsules at a relatively low rate. Normally, the
rate of passage of the drug through the walls of the microcapsules
is dependent on the solubility of the drug therein or the porosity
of the wall, as well as on the microcapsule wall thickness. This
means that selection of appropriate encapsulating materials will be
dependent on the particular drug used in the bandage. By varying
the encapsulating material and the wall thickness, the dosage rate
per area of bandage can be controlled and movement of drug to the
adhesive regulated.
Suitable materials for use in encapsulating the drug include
hydrophobic polymers such as polyvinylchloride either unplasticized
or plasticized with long-chain fatty amides or other plasticizer;
plasticized nylon; unplasticized soft nylon; silicone rubber;
polyethylene, and polyethylene terephthalate; and hydrophilic
polymers such as esters of acrylic and methacrylic acid (as
described in U.S. Pat. Nos. 2,976,576 and 3,220,960 and Belgian
Pat. No. 701,813); modified collagen; cross-linked hydrophilic
polyether gels (as described in U.S. Pat. No. 3,419,006);
cross-linked polyvinylalcohol; and cross-linked partially
hydrolyzed polyvinylacetate.
To provide the microcapsules, the encapsulating material can be
uniformly impregnated with the drug to form microcapsules which are
a matrix having the drug distributed therethrough. Alternatively,
particles of drug can be encapsulated with thin coatings of the
encapsulating material to form microcapsules having an interior
chamber containing the drug. If desired, particles of a matrix,
such as starch, gum acadia, gum tragacanth, and polyvinylchloride,
can be impregnated with the drug and encapsulated with other
materials such as the encapsulating materials previously described
which function as a solubility membrane to meter the flow of drug
to the adhesives; use of a matrix and a different solubility
membrane coating can slow the passage of the drug from the
microcapsules which is desirable with drugs that are released too
rapidly from available encapsulating materials.
Any of the encapsulation or impregnation techniques known in the
art can be used to prepare the microcapsules to be incorporated
into the pressure-sensitive adhesive in accord with the embodiment
of FIGS. 1 and 2. Thus, the drug can be added to the encapsulating
material in liquid form and uniformly distributed therethrough by
mixing and subsequently converting to a solid by curing or cooling;
or solid encapsulating material can be impregnated with a drug by
immersion in a bath of the drug to diffuse into the material.
Subsequently, the solid material can be reduced to fine
microcapsules by grinding, each of the microcapsules comprising
drug coated with and distributed throughout the encapsulating
material. Alternatively, fine particles of the drug can be
encapsulated with the coating. One suitable technique comprises
suspending dry particles of the drug in an air stream and
contacting that stream with a stream containing the encapsulating
material to coat the drug particles. Usually, the microcapsules
have an average particle size of from 1 to 1,000 microns, although
this is not critical to the invention.
Further embodiments of the adhesive bandage of the invention are
illustrated in FIGS. 3, 4 and 5. As illustrated in FIG. 3, adhesive
bandage 20 of the invention is comprised of topically active agent
24 uniformly distributed in a reservoir 22 which is a polymeric
matrix material. The matrix material is laminated to backing member
21 and bears a pressure-sensitive adhesive coating 23 thereon. The
polymeric matrix material has a release rate for the particular
drug used which continuously controls the releasing drug.
FIG. 4 illustrates a further modified form of the invention wherein
the adhesive bandage 30 of the invention is comprised of a backing
member 21 having a reservoir 32 on one surface thereof. A
solubility member 35 is interposed between the reservoir 32 and a
pressure-sensitive adhesive coating 23. Topically active agent 24
is confined in polymeric matrix material 32 which acts as the
reservoir for the drug.
FIG. 5 illustrates a further form of the bandage 40 including a
backing member 21 and a reservoir 42 in the form of a hollow
container having an interior chamber 43 containing topically active
agent 34. Wall 45 of reservoir 42, remote from backing member 21,
is permeable to passage of drug 34, as by diffusion, to meter the
flow of drug to pressure-sensitive adhesive layer 23 on the outer
surface thereof. This form of the bandage is less preferred since
it cannot conveniently be cut to fit precisely the size of skin
lesions to which applied. However, it is satisfactory for
application to large areas of skin.
Suitable materials for forming the reservoir, whether of the matrix
or hollow container type, are those materials permeable to passage
of the drug previously described as suitable encapsulating
materials. The reservoir can be formed by molding into the form of
a hollow container with the drug trapped therein. Alternatively,
the reservoir can be in the form of an envelope formed from sheets
of polymeric material permeable to passage of the drug and
enclosing the drug. While the walls of the reservoir can be of any
convenient thickness, usually they have a thickness of from 0.01 to
7 millimeters. When the reservoir comprises a matrix with the drug
distributed therethrough, it can be prepared by adding the drug to
the matrix material in liquid form or solvent solution form and
subsequently converting the matrix to a solid by curing, cooling or
evaporation of solvent.
Thus, the reservoir of the bandage is a hollow drug container or a
solid matrix. Drug is metered from the reservoir to the adhesive
layer, at a rate controlled by the composition and thickness of the
reservoir or of the reservoir wall. From the adhesive layer, drug
is directly transmitted to the skin to which the bandage is
applied.
In the embodiment of the invention illustrated in FIG. 4, metering
of the drug from the reservoir to the adhesive is further
controlled by interposing a further solubility membrane
therebetween. The solubility membrane is formed of a material in
which the drug is soluble and capable of diffusing through. Any of
the materials previously mentioned for use in microencapsulation
may be used as the solubility membrane. Of course, in each
instance, the solubility membrane will have different
characteristics than the reservoir wall of the particular device.
This use of a pair of solubility membranes, that is, the reservoir
wall and the further solubility membrane, allows for precise
metering of drug to the adhesive layer; for the thickness and
composition of both membranes can be varied to provide for wide
range of dosage levels for a given area of bandage. It will be
appreciated that this solubility membrane can be used with either
the matrix or container type of reservoir.
In practicing this invention one can employ a wide variety of
topically active drugs consistent with their known dosages and
uses. Suitable drugs include, without limitation: Antiperspirants,
e.g. aluminum chloride; Deodorants, e.g. hexachlorophene,
methylbenzethonium chloride; Astringents, e.g. tannic acid;
Irritants, e.g. methyl salicylate, camphor, cantharidin;
Keratolytics, e.g. benzoic acid, salicylic acid, resorcinol,
iodochlorhydroxyguin; Antifungal Agents such as tolnaftate,
griseofulvin, nystatin and amphotericin; Anti-Inflammatory Agents,
such as corticosteroids, e.g. hydrocortisone, hydrocortisone
acetate, prednisolone, methylprednisolone, triamcinolone acetonide,
fluidrocortisone, flurandrenolone, flumethasone, dexamethasone
sodium phosphate, bethamethasone valerate, fluocinolone acetonide;
fluorometholone; and pramoxine HCl; and Antibacterial Agents, such
as bacitracin, neomycin, erythromycin, tetracycline HCl,
chlortetracycline HCl, chloramphenicole, oxytetracycline, polymyxin
B, nitrofurazone, mafenide (.alpha.-amino-p-toluenesulfonamide),
hexachlorophene, benzalkonium chloride, cetalkonium chloride,
methylbenzethonium chloride, and neomycin sulfate.
In addition to the aforementioned drugs, simple pharmacologically
acceptable derivatives of the drugs, such as ethers, esters,
amides, acetals, salts, etc., or formulations of these drugs,
having the desired polymeric permeability or transport properties
can be prepared and used in practicing the invention. Drugs
mentioned above can be used alone or in combination with others and
each other.
The amount of topically active agent to be incorporated in the
bandage to obtain the desired therapeutic effect will vary
depending upon the desired dosage, the permeability of the
polymeric materials of the bandage which are employed to the
particular agent to be used, and the length of time the bandage is
to remain on the skin. The effective rate or release of the active
agent to the skin can be in the range of from 0.5 to 1,000
micrograms per square centimeter of bandage per day. The exact
amount will depend on the desired dosage as well as the area of the
skin to be treated. These effective rates of release of active
agent to the skin can be obtained by altering the permeability and
thickness of the release rate controlling barrier. In the case of
the microencapsulated active agent, the release rate can also be
controlled by varying the number of microcapsules present in a
given volume of the matrix of the device. This is a particular
desirable feature of this aspect of the invention. Additionally,
the duration of action of the device can be altered by controlling
the amount of active agent initially incorporated consistent with
the release rate. Further, the release rate of drug as well as the
duration of release of the drug from the device can be
predetermined to be in consonance with the optimum therapeutic
values. Once this dosage level in micrograms per square centimeter
of bandage has been determined, the total amount of drug to be
incorporated in the bandage can be established by obtaining the
release rate of the agent in the particular material or materials
which are to be used.
Those skilled in the art can readily determine the rate of
permeation of agent through a polymeric material or selected
combinations of polymeric materials. One method that has been found
to be eminently well suited is to cast or hot press a film of the
material to a thickness in the range of 2 to 60 mils. The film is
used as a barrier between a rapidly stirred (e.g. 150 r.p.m.)
saturated solution of the drug containing excess solid drug (or a
concentrated solution of the drug) and a rapidly stirred solvent
bath, both maintained at constant temperature (typically 37.degree.
C). Samples are periodically withdrawing from the solvent bath and
analyzed for drug concentration. By plotting drug concentration in
the solvent bath versus time, the permeability constant P of the
membrane is determined by the Fick's First Law of Diffusion.
Slope of plot = Q.sub.1 - Q.sub.2 /t.sub.1 - t.sub.2 = p (AC/h)
I
wherein
Q.sub.1 = cumulative amount of drug in solvent in micrograms at
t.sub.1
Q.sub.2 = cumulative amount of drug in solvent in microgram at
t.sub.2
t.sub.1 = elapsed time to first sample i.e. Q.sub.1
t.sub.2 = elapsed time to second sample i.e. Q.sub.2
A = area of membrane in cm.sup.2
C = saturation concentration of drug in solution
h = thickness of membrane in cm.
By determining the slop of the plot i.e. Q.sub.1 - Q.sub.2 /t.sub.1
- t.sub.2 and solving the equation using the known or measured
values of A, C, and h, the permeability P constant in cm.sup.2
/time of the material or membrane for a given compound is readily
determined. Of course, this permeability constant is an inherent
characteristic of the material for a given compound.
Using the above technique, the permeability constant P of
hydrocortisone from isotonic solution through different membranes
into isotonic solution at 37.degree. C was found to be:
Membrane Permeability Constant (cm.sup.2 /hr) Silicone Rubber
.sup.1 835 Aromatic Polyamide .sup.2 10 .sup.1 Down Corning -
HH0717 .sup.2 Allied Chemical - Capran
Using the above technique and data, the permeability constant P for
a select membrane and drug can be determined. These data can then
be employed to design a device of the invention to release the
agent to the skin in the desired dosage range. Similarly, this
experimental procedure or others known to those skilled in the art
can be used to determine release rates for the suitable polymeric
materials as above disclosed in order to design the bandage of this
invention.
Other methods of the determining passage of drugs by diffusion
through drug permeable polymeric material are available. See Dziuk,
P. J. and Cook, B., Passage of Steroids Through Silicone Rubbers,
Endocrinology, 78:208, 1966; U.S. Pat. No. 3,279,996; Folkman and
Edmonds, Circulation Research 10:632, 1962; Folkman and Long, J.
Surg. Res. 43:139, 1964; Powers, J. Parasitology 51:53 April,
1965), No. 2 Section 2.
Any of the well-known dermatologically acceptable permeable
pressure-sensitive adhesives which permit drug migration can be
used in practicing this invention. Exemplary adhesives include
acrylic or methacrylic resins such as polymers of esters of acrylic
or methacrylic acid with alcohols such as n-butanol, n-pentanol,
isopentanol, 2-methyl butanol, 1-methyl butanol, 1-methyl pentanol,
2-methyl pentanol, 3-methyl pentanol, 2-ethyl butanol, isooctanol,
n-decanol, or n-dodecanol, alone or copolymerized with
ethylenically unsaturated monomers such as acrylic acid,
methacrylic acid, acrylamide, methacrylamide, N-alkoxymethyl
acrylamides, N-alkoxymethyl methacrylamides, N-tert.
butylacrylamide, itaconic acid, vinylacetate, N-branched alkyl
maleamic acids wherein the alkyl group has 10 to 24 carbon atoms,
glycol diacrylates, or mixtures of these; natural or synthetic
rubbers such as silicone rubber, styrene-butadiene, butyl-ether,
neoprene, polyisobutylene, polybutadiene, and polyisoprene;
polyurethane elastomers; vinyl polymers, such as polyvinylalcohol,
polyvinyl ethers, polyvinyl pyrrolidone, and polyvinylacetate;
ureaformaldehyde resins; phenolformaldehyde resins; resorcinol
formaldehyde resins; cellulose derivatives such as ethyl cellulose,
methyl cellulose, nitrocellulose, cellulose acetatebutyrate, and
carboxymethyl cellulose; and natural gums such as guar, acacia,
pectins, starch, dextrin, albumin, gelatin, casein, etc. The
adhesives may be compounded with tackifiers and stabilizers as is
well known in the art.
Various occlusive and non-occlusive, flexible or non-flexible
backing members can be used in the adhesive bandage of the
invention. Suitable backings include cellophane, cellulose acetate,
ethylcellulose, plasticized vinylacetate-vinylchloride copolymers,
polyethylene terephthalate, nylon, polyethylene, polypropylene,
polyvinylidenechloride, paper, cloth, and aluminum foil.
Preferably, a flexible occlusive backing is employed to conform to
the shape of the body member to which the adhesive tape is applied
and to enhance administration of the agent to the skin.
To prevent passage of the drug away from the exposed surface of the
pressure-sensitive adhesive prior to use, the adhesive surface of
the tape generally is covered with a protective release film or
foil, such as waxed paper. Alternatively, the exposed rear surface
of the backing member can be coated with a low-adhesion backsize
and the bandage rolled about itself. To enhance stability of the
active compounds, the therapeutic bandage usually is packaged
between hermetically sealed polyethylene terephthalate films under
an inert atmosphere, such as gaseous nitrogen.
To use the adhesive bandage of the invention, it is applied
directly to skin, to release a therapeutically effective amount of
the agent to the affected area. By use of this invention, one
ensures that an accurately measured quantity of the active drug is
available when the bandage is applied to the skin.
The following examples will serve to illustrate the invention
without in any way being limiting thereon.
EXAMPLE I
2-hydroxyethyl methacrylate (100 grams) is diluted with water (100
grams) and mixed with tertiary butyl peroctoate (0.20 gram).
Ethylene glycol dimethacrylate (0.20 gram) is added along with 4
grams of sodium bicarbonate as a foaming agent. The mixture is
heated to 70.degree. C under an atmosphere of nitrogen and the
resulting solid, friable polymeric foam is ground into fine powder
of 20 micron average particle size. The polymeric powder (10 grams)
is mixed with neomycin (2 grams) dissolved in a mixture of ethyl
alcohol: water (50:50) and the resultant mixture placed on a
mechanical roller until the polymeric powder has absorbed the drug.
The solution is then filtered.
The resulting microcapsules of neomycin are mixed with 100 grams of
a 22 percent solution in hexane: isopropylacetate (70:30) of a
viscoelastic copolymer of isooctyl acrylate and acrylic acid (94:6)
adhesive to uniformly distribute the microcapsules throughout the
adhesive solution. The resulting slurry is coated onto a cellophane
sheet 10 centimeters in width by 100 centimeters in length and the
solvent removed by evaporation from the coated film.
When applied to the infected skin area of a subject, the resulting
bandage is effective to control the continuous administration of a
daily therapeutically effective dosage of neomycin to the skin.
EXAMPLE II
Liquid dimethyl silicone polymeric rubber (100 grams, Dow-Corning
Silastic) is mixed with 5 grams of nitrofurazone. After uniformly
mixing the drug with unvulcanized silicone rubber, 0.5 gram of
stannous octoate catalyst is added and the rubber cured at room
temperature. The resulting silicone rubber body is reduced to an
average particle size of 100 microns. Pressure-sensitive adhesive
composition is prepared by adding to 100 milliliters of hexane the
following:
20 grams of polyvinylethyl ether (reduced visosity= 5.0 .+-.
0.5)
4 grams of polyvinylethylether (reduced viscosity= 0.3 .+-.
0.1)
4 grams of glycerol ester of hydrogenated rosin and 2 grams
polyethylene glycol 400
Ten grams of the resulting nitrofurazone capsules are mixed with
pressure-sensitive adhesive prepared above to uniformly distribute
the microcapsules throughout the adhesive. Immediately thereafter,
the adhesive mixture is coated onto one surface of a 1,000 square
centimeter Mylar sheet. The resulting bandage can be used for
control of skin infections.
EXAMPLE III
Ten milligrams of betamethasone is placed on a sheet of dimethyl
silicone rubber having a thickness of 0.13 millimeters. The sheet
is folded to provide a surface area of 100 square centimeters on
each face and the flaps sealed with silicone adhesive to provide a
thin envelope containing the drug.
Pressure-sensitive adhesive is prepared by mixing together, 90
grams of polyacrylate solution (ethylacetate: hexane/5:1)
containing 25 percent non-volatile matter, (obtained by the
catalytic polymerization of isoamylacrylate and acrylic acid in the
ratio of 95:5 in ethylacetate and then diluting with hexane), 5
grams polyvinylethylether (reduced viscosity= 0.3 .+-. 0.1), 1 gram
castor oil (USP) and 4 grams polyethyleneglycol 400.
One face surface of the envelope is bonded to a sheet of cellophane
while the other is coated with adhesive prepared above to a
thickness of 2 millimeters. The adhesive face surface of the
bandage has an area of 100 square centimeters. The bandage is
effective to release a therapeutically effective daily dosage of
the drug when applied to the skin for control of psoriasis.
Thus, this invention provides a reliable and easy to use device for
administering topically active drugs directly to the skin.
Uncertainties resulting from topical application of these agents,
from creams and solutions, are not encountered; and a precisely
determined amount of the drug is applied in a controlled
manner.
Although the product of this invention has been referred to as an
adhesive bandage, those skilled in the art will appreciate that the
term "adhesive bandage" as used herein includes any product having
a backing member and a pressure-sensitive adhesive face surface.
Such products can be provided in various sizes and configurations,
including tapes, bandages, sheets, plasters, and the like.
While there have been shown and described and pointed out the
fundamental novel features of the invention as applied to the
preferred embodiment, it will be understood that various omissions
and substitutions and changes in the form and details of the
adhesive tape illustrated may be made by those skilled in the art
without departing from the spirit of the invention. It is the
intention, therefore, to be limited only as indicated by the scope
of the following claims.
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