U.S. patent number 3,598,123 [Application Number 04/812,117] was granted by the patent office on 1971-08-10 for bandage for administering drugs.
This patent grant is currently assigned to ALZA Corporation. Invention is credited to Alejandro Zaffaroni.
United States Patent |
3,598,123 |
Zaffaroni |
August 10, 1971 |
BANDAGE FOR ADMINISTERING DRUGS
Abstract
Bandage for use in the continuous administration of drugs by
absorption comprising a backing member bearing a pressure-sensitive
adhesive layer on one surface thereof. Distributed throughout the
pressure-sensitive adhesive are microcapsules comprised of a
systemically active drug encapsulated with a material permeable to
passage of the drug. The drug is in a form acceptable for
absorption through the skin or the mucosa of the mouth.
Inventors: |
Zaffaroni; Alejandro (Atherton,
CA) |
Assignee: |
ALZA Corporation (N/A)
|
Family
ID: |
25208557 |
Appl.
No.: |
04/812,117 |
Filed: |
April 1, 1969 |
Current U.S.
Class: |
424/435; 424/448;
604/304; 401/132; 424/449 |
Current CPC
Class: |
A61K
9/7092 (20130101); A61L 15/58 (20130101); A61K
9/7061 (20130101); A61K 9/7069 (20130101) |
Current International
Class: |
A61K
9/70 (20060101); A61L 15/58 (20060101); A61L
15/16 (20060101); A61f 007/02 () |
Field of
Search: |
;128/155--156,268,296
;424/19--20,28 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Rosenbaum; Charles F.
Claims
What I claim is:
1. A medical bandage for use in the continuous administration to
circulation of controlled quantities of systemically active drugs
over a prolonged period of time by absorption through the external
body skin or mucosa, said bandage comprising (1) a backing member
bearing (2) a pressure-sensitive adhesive on one surface thereof,
said pressure-sensitive adhesive having distributed therethrough
(3) a plurality of discrete microcapsules, each of which
microcapsules comprising a systemically 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 microcapsules to the skin or mucosa at a
controlled and predetermined rate over a prolonged period of
time.
2. The bandage as defined by claim 1, wherein each of said
microcapsules (3) is comprised of systemically active drug
formulation microencapsulated with the said drug release rate
controlling wall material.
3. The bandage as defined by claim 1, wherein each of said
microcapsules (3) is comprised of a matrix of the drug release rate
controlling wall material, said matrix having the systemically
active drug formulation distributed therethrough.
4. The bandage as defined by claim 1, wherein the systemically
active drug formulation is soluble in the drug release rate
controlling material.
5. The bandage as defined by claim 1, wherein the
pressure-sensitive adhesive is permeable to passage of the
systemically active drug formulation.
6. The bandage as defined by claim 1, wherein the drug formulation
comprises a pharmacologically acceptable solvent.
7. The bandage as defined by claim 1, wherein said drug release
rate controlling material is silicone rubber.
8. The bandage as defined by claim 1, wherein said drug release
rate controlling material is a hydrophilic polymer of an ester of
an olefinic acid.
9. The bandage as defined by claim 1, wherein the
pressure-sensitive adhesive is adapted to provide a liquidtight
adhesive seal between the skin or mucosa and the bandage.
10. The bandage as defined by claim 1, wherein the surface of a
pressure-sensitive adhesive (3) is covered with a protective
release coating (4).
11. The bandage as defined by claim 1, wherein the outer surface of
the backing member (1) is coated with a low adhesion backsize
(5).
12. The bandage as defined by claim 1, wherein said microcapsules
have an average particle size of from 1 to 1,000 microns.
13. The bandage as defined by claim 1, wherein the adhesive face of
the bandage has an area of 0.5 to 400 square centimeters.
Description
BACKGROUND OF THE INVENTION
This invention relates to a bandage for use in the continuous
administration of systemically active drugs.
One primary objective of drug therapy is to achieve a particular
(uniform, variable, or modulated) blood level of drug in
circulation for a period of time (hours, days, months). Many drugs,
such as the steroidal hormones, are absorbed in a relatively short
period of time, and are not long acting due to rapid metabolism and
excretion following administration. To obtain the desired
therapeutic effect, it is necessary in most cases to establish a
dosage regime of multiple unit doses over a 24 hour period. Most
drugs are administered orally or by injection and neither of these
modes of administration achieves the desired blood level of drug in
circulation in the typical case.
With oral administration of drugs, it is difficult if not
impossible to achieve a constant blood level of drug in
circulation. This is true even though the drug is administered at
periodic intervals according to a well-defined schedule. One reason
for this is that the rate of absorption of drugs through the
gastrointestinal tract is affected by the contents of the tract.
Such variables as whether the drug is administered before or after
eating and the type and quantity of food eaten (for example, high
or low fat content) or administered before or after a bowel
movement, can control the rate of absorption of the drug in the
gastrointestinal tract. As most of the absorption of drugs takes
place in the small intestine, the time of passage through the small
intestine is another governing factor. This in turn is affected by
the rate of peristaltic contracting, adding further uncertainty.
Also important is the rate of circulation of blood to the small
intestine.
The almost inevitable result of oral administration of drugs
through the gastrointestinal tract is that the level of drug in
circulation surges to a high each time the drug is administered,
followed by a decline in concentration in the blood and body
compartments. Thus, a plot of drug in circulation following a
dosage schedule of several tablets a day has the appearance of a
series of peaks, which may surpass the toxic threshold, and
valleys. Each time the blood level decreases below a critical point
needed to achieve the desired therapeutic effect that effect will
no longer be obtained. Worse still, with antimicrobial drugs, the
disease-producing micro-organisms rapidly multiply when the
concentration of drug in circulation descends below a critical
point. It is likely that the drug-resistant mutant strains which
are becoming increasingly prevalent and represent one of the major
problems in the therapeutics of infectious diseases are formed
precisely at such times.
One approach to this problem has been the advent of the so-called
sustained release or time-capsule in oral dosage form. While many
of these perform satisfactorily in vitro and in animal or clinical
studies under controlled conditions of nutrition and activity,
there is little or no evidence that these dosage forms are
effective for achieving a continuous and predictable level of drug
in circulation over a prolonged period of time under the normal
conditions encountered by the outpatient.
Many effective therapeutic agents are destroyed by microbial flora
of G.I. secretions or are poorly absorbed in the gastrointestinal
tract.
Administration of drugs by injection is inconvenient, painful, and
the risk of local tissue reaction and of infection is serious.
Moreover, the typical result of administration by injection is a
surge in blood level concentration of the drug immediately after
injection, followed by a decline and another surge in concentration
upon subsequent injections.
Other dosage forms such as rectal suppositories and sublingual
lozenges also produce nonuniform levels of the therapeutic agent in
circulation. These dosage forms require great patient cooperation,
have low patient acceptability, and are sparingly used throughout
most of the world.
Dosage forms described above all bring about a pulse entry of drug,
that is, a concentrated dose of drug is brought into contact with
an organ of entry at a particular time unit. Undoubtedly, this
creates drug concentrations beyond the capacity of the active
centers to accept (that is, the saturation point is exceeded by
many orders of magnitude) and, also, until dilution in body fluids
takes place, may exceed the capacity of metabolic and excretory
mechanisms. The result is that a toxic level of drug is allowed to
build, for a period of time, with detrimental effects for
particular tissues or organs. To obtain persistence of effect, the
usual industrial approach is to make the initial dose high or to
modify the drug structure to obtain a longer metabolic half-life of
the drug in circulation long. Raising the initial dosage only
worsens the problem. Many derivatives with long half-lives have a
lower therapeutic index (ratio between the median toxic dose and
the median effective dose) than that of the parent compounds; and
therefore these approaches are not the answer to the problem.
To avoid the problems discussed above, it has been suggested that
systemically active drugs can be administered through the skin.
Percutaneous administration can have the advantage of permitting
continuous administration of drug to circulation over a prolonged
period of time to obtain a uniform delivery rate and blood level of
drug. Commencement and termination of drug therapy are initiated by
the application and removal of the dosing device from the skin.
Uncertainties of administration through the gastrointestinal tract
and the inconvenience of administration by injection are
eliminated. Since a high concentration of drug never enters the
body, problems of pulse entry are overcome and metabolic half-life
is not a factor of controlling importance.
Despite these advantages of administering systemically active drugs
through the skin, prior devices designed for this purpose were
either impractical or inoperative and did not provide continuous
administration and delivery rate. This form of administration has
not been accepted by the medical profession and the only prior art
manner of obtaining continuous delivery rate remains the continuous
intravenous drip.
SUMMARY OF THE INVENTION
Accordingly, an object of this invention is to provide a device for
the administration of systemically active drugs which overcomes the
aforesaid disadvantages inherent in prior art modes of
administration.
Another object of this invention is to provide a reliable and
easily applied device for continuously administering controlled
quantities of systemically active drugs through the skin.
Still another object of this invention is to provide a device for
administering systemically active drugs through the oral
mucosa.
A further object of this invention is to provide a complete dosage
regime for a particular time period, the use of which requires
patient intervention only for initiation and termination.
In accomplishing these objects, one feature of this invention
resides in a bandage for use in the continuous administration of
systemically active drugs by absorption. The bandage is comprised
of a backing member bearing a pressure-sensitive adhesive layer on
one surface thereof. The pressure-sensitive adhesive has
distributed therethrough microcapsules acting as an external drug
reservoir and comprising a systemically active drug encapsulated
with a material permeable to passage of the drug. The drug is in a
form suitable for absorption through the skin or oral mucosa.
Other objects, features, and advantages of the invention will be
apparent to those skilled in the art from the detailed description
of the invention which follows, and from the drawings.
BRIEF DESCRIPTION OF DRAWINGS
In the drawings:
FIG. 1 is a perspective view of the bandage of the invention
and
FIG. 2 is a cross-sectional view of the bandage of the
invention.
As illustrated in FIGS. 1 and 2, the bandage 10 of this invention
is comprised of a backing member 11 bearing a pressure-sensitive
adhesive layer 12 on one surface thereof. Adhesive layer 12 has
microcapsules 13 of a systemically active drug encapsulated with a
material permeable to passage of the drug uniformly distributed
therethrough.
DETAILED DESCRIPTION OF THE INVENTION
To use the bandage 10 of the invention, it is applied to the
patient's skin. Adhesive layer 12 should be in firm contact with
the skin, forming a tight seal therewith. Drug within microcapsules
13, whether in solid form or solution, migrates through the walls
of the microcapsules, acting as a solubility membrane, and into
adhesive layer 12, as by diffusion. Ordinarily, one would expect
the drug migration to cease when sufficient drug has reached the
outer surface of microcapsules 13 to create an equilibrium or when
adhesive layer 12 has become saturated with the drug. However, when
adhesive layer 12 is in contact with the patient's skin, drug
molecules which are continuously removed from the outer surface of
microcapsules 13 migrate through the adhesive to the outer surface
of the adhesive layer and are absorbed by the skin. Absorbed drug
molecules pass through the skin and enter circulation through the
capillary network. While the bandage may be applied to any area of
the patient's skin, the lower back and buttocks are the areas of
choice. In like manner, the bandage can be applied to the mucosa of
the mouth, for example, by application to the palate or the buccal
mucosa, to obtain absorption of the drug by the oral mucosa.
Although obtaining a liquidtight adhesive seal between the skin and
bandage is important, it becomes critical in the mouth. Without
such a seal, irrigation of the oral mucosa by saliva will transfer
the drug to the gastrointestinal tract, rather than to circulation
through the oral mucosa.
Those skilled in the art will appreciate that the bandage of this
invention significantly differs from prior art wound dressings or
bandages containing antiseptics or topically active drugs. The
bandage of this invention contains an encapsulated systemically
active drug and is applied to unbroken skin, to introduce the drug
to circulation in the bloodstream and produce a pharmacologic
response at a site remote from the point of application of the
bandage. Thus, the bandage functions as an external drug reservoir
and provides a complete dosage regime for a particular time
period.
In practicing this invention, one can employ any systemically
active drug which will be absorbed by the body surface to which the
bandage is applied. The term "systemically active drug" is used
herein in its broadest sense as indicating a substance or
composition which will give a pharmacologic response at a site
remote from the point of application of the bandage. Of course, the
amount of drug necessary to obtain the desired therapeutic effect
will vary depending on the particular drug used. Suitable drugs
include, without limitation, antimicrobial agents such as
penicillin, tetracycline, oxytetracycline, chlortetracycline,
chloramphenicol, and sulfonamides; sedatives and hypnotics such as
pentabarbital sodium, phenobarbital, secobarbital sodium, codeine,
(.alpha.-bromo-isovaleryl) urea, carbromal, and sodium
phenobarbital; psychic energizers such as 3-(2-aminopropyl) indole
acetate and 3-)2-aminobutyl) indole acetate; tranquilizers such as
reserpine, chlorpromazine hydrochloride, and thiopropazate
hydrochloride; hormones such as adrenocorticosteroids, for example,
6.alpha.-methylprednisolone, cortisone, cortisol, and
triamcinolone; androgenic steroids, for example,
methyltestosterone, and fluoxymesterone; estrogenic steroids, for
example, estrone, 17.beta.-estrodiol and ethinyl estradiol;
progestational steroids, for example, 17.alpha.-hydroxyprogesterone
acetate, medroxyprogesterone acetate, 19-norprogesterone, and
norethindrone; and thyroxine; antipyretics such as aspirin,
salicylamide, and sodium salicylate; antispasmodics such as
atropine, methscopolamine bromide, methscopolamine bromide with
phenobarbital; antimalarials such as the 4-aminoquinolines,
8-aminoquinolines, and pyrimethamine; and nutritional agents such
as vitamins, essential amino acids, and essential fats.
Drugs which alone do not pass through the skin or oral mucosa can
be dissolved in an absorbable, pharmacologically acceptable solvent
to achieve passage through the external body layer. Suitable
solvents include alcohols containing 2 to 10 carbon atoms, such as
hexanol, cyclohexanol, benzylalcohol, 1,2-butanediol, glycerol, and
amyl alcohol; hydrocarbons having 5 to 12 carbon atoms such as
n-hexane, cyclohexane, and ethyl benzene; aldehydes and ketones
having 4 to 10 carbon atoms such as heptyl aldehyde, cyclohexanone,
and benzaldehyde; esters having 4 to 10 carbon atoms such as amyl
acetate and benzyl propionate; ethereal oils such as oil of
eucalyptus, oil of rue, cumin oil, limonene, thymol, and 1-pinene;
halogenated hydrocarbons having two to eight carbon atoms such as
n-hyxyl chloride, n-hexyl bromide, and cyclohexyl chlorides; or
mixtures of any of the foregoing solvents. Also, with drugs which
do not pass through the skin or oral mucosa, simple
pharmacologically acceptable derivatives of the drugs, such as
ethers, esters, amides, acetals, etc. having the desired absorption
property can be prepared and used in practicing the invention. Of
course, the derivatives should be such as to convert to the active
drugs within the body through the action of body enzyme assisted
transformations, pH, etc.
Materials used to encapsulate the drug or drug solution 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 or drug solution therein, 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.
One presently preferred class of encapsulating materials are the
organopolysiloxane rubbers, commonly known as silicone rubbers.
Suitable silicone rubbers are the conventional heat-curable
silicone rubbers and the room-temperature-vulcanizable silicone
rubbers.
Conventional silicone rubbers which are converted to the rubbery
state by the action of heat are predominantly linear
organopolysiloxanes having an average degree of substitution of
about two organic groups attached directly to silicon per silicon
atom. Preferably, the organic groups are monovalent hydrocarbon
radicals such as alkyl, aryl, alkenyl, alkaryl, aralkyl, and of
these, the methyl, phenyl and vinyl radicals are most
preferred.
Variation of the organic groups in the silicone rubber can be used
to vary the solubility of the drug in the polymer and hence can
control the speed of migration of the drug through the polymer.
Also, drugs which are insoluble in one type of silicone rubber may
be soluble in a different type of polymer. One especially preferred
class of silicone polymers are the pure dimethylpolysiloxanes.
Room-temperature-vulcanizable silicone rubbers are also
commercially available and are known to the art. In general, they
employ the same silicone polymers as discussed above although the
polymers often contain a greater amount of silicon-bonded hydroxy
groups. This type of silicone rubber will cure at room temperature
in the presence of an appropriate catalyst, such as stannous
2-ethylhexoate.
Exemplary patents disclosing the preparation of silicone rubbers
are U.S. Pat. Nos. 2,541,137, 2,723,966, 2,863,846, 2,890,188,
2,927,907, 3,002,951, and 3,035,016.
Another class of materials suitable for encapsulating drugs are the
hydrophilic polymers of monoesters of an olefinic acid, such as
acrylic acid and methacrylic acid. Exemplary polymers of this class
include poly (hydroxyethylacrylate) and poly
(hydroxyethylmethacrylate). These polymers are commercially
available and their preparation is described in U.S. Pat. Nos.
2,976,576 and 3,220,960, as well as in Belgian Pat. No. 701,813.
When using these hydrophilic polymers, the drug is normally
dissolved in a solvent such as a lower alcohol to promote passage
of the drug through the polymer.
Other exemplary materials for use as encapsulating media in this
invention include polyvinylalcohol, polyvinylacetate, plasticized
polyvinylchloride, plasticized nylon, collagen, modified collagen,
gelatin, and waxes such as polyethylene wax, oxidized polyethylene
wax, hydrogenated castor oil, etc.
To provide the microcapsules, the encapsulating materials can be
uniformly impregnated with the drug or drug solution to form
microcapsules which are a matrix having the drug distributed
therethrough. Alternatively, particles or solutions of drugs 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 acacia, gum
tragacanth, and polyvinylchloride, can be impregnated with the drug
and encapsulated with another material such as the encapsulating
materials previously discussed which function as a solubility
membrane to meter the flow of drug to the adhesives; use of a
matrix and a different solubility membrane can slow the passage of
the drug from the microcapsules which is desirable with drugs that
are released too rapidly from available encapsulating materials. In
contrast, by encapsulating a solution of the drug, the solvent
speeds passage of the drug through the microcapsule walls.
Any of the encapsulation or impregnation techniques known in the
art can be used to prepare the microcapsules to be incorporated
into the adhesive base in accord with this invention. Thus, the
drug or drug solution can be added to the encapsulating material in
liquid form and uniformly distributed therethrough by mixing; or
solid encapsulating material can be impregnated with the drug by
immersion in a bath of the drug to cause 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 or solutions
of the drug can be encapsulated with a coating. One suitable
technique comprises suspending dry particles of the drug in an
airstream 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.
The microcapsules, however made, are then mixed with a
pressure-sensitive adhesive. Any of the well-known dermatologically
acceptable pressure-sensitive adhesives which permit drug migration
can be used in practicing this invention. Exemplary adhesives
include acrylic resins such as polymers of esters of acrylic 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-deconal, 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; elastomeric silicone polymers; polyurethane elastomers;
rubbery polymers, such as polyisobutylene, polyisoprene, and
polybutadiene; vinyl polymers, such as polyvinylalcohol, polyvinyl
pyrrolidone, and polyvinylacetate; cellulose derivatives such as
ethyl cellulose, methyl cellulose, and carboxymethyl cellulose;
natural gums such as guar, acacia, pectins, etc. For use in contact
with the oral mucosa rubbery polymers, such as polyisobutylene,
with or without gum modifiers gives good results, as do polyvinyl
alcohol, polyvinyl pyrrolidone, cellulose derivatives and others.
The adhesives may be compounded with tackifiers and stabilizers as
is well known in the art.
The mixture of microcapsules and pressure-sensitive adhesive is
then coated onto a backing member, usually to provide an adhesive
layer 0.01 to 7 millimeters thick, although these limits can be
exceeded if more or less drug is required. The purpose of the
backing is to provide support for the bandage and to prevent
passage of the drug through the adhesive surface away from the body
surface to which the bandage is applied. Backing members can be
flexible or nonflexible and suitable materials include cellophane,
cellulose acetate, ethyl cellulose, plasticized vinyl acetate-vinyl
chloride copolymers, polyethylene terephthalate, nylon,
polyethylene, polyvinylidene chloride, coated flexible fibrous
backings such as paper and cloth, and aluminum foil.
The required surface area of the bandage will depend on the
activity of the drug and the rate of its absorption through the
skin. Usually, the adhesive face of the bandage has a surface area
of 0.5 to 400 square centimeters, although smaller or larger area
bandages can be used.
It will be appreciated that on encapsulating the drug with a
material, such as silicone rubber, the drug immediately begins to
migrate into and through the encapsulating material. On mixing the
microcapsules with the adhesive the drug passing through the walls
of the microcapsules will enter the adhesive, eventually saturating
the adhesive with the drug. To prevent passage of the drug away
from the exposed surface of the adhesive prior to use, the adhesive
surface of the bandage generally is covered with a protective
release film or foil, such as waxed paper, prior to use.
Alternatively, the exposed rear surface of the backing member can
be coated with a low-adhesion backsize and the bandage rolled about
itself.
The following examples will serve to illustrate the invention
without in any way being limiting thereon.
EXAMPLE I
2-hydroxyethyl methacrylate (100 grams) is 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. and the
resulting solid, firable polymeric foam is ground into fine powder
of 20-micron average particle size. The polymeric powder (10 grams)
is mixed with chloramphenicol antibiotic (2 grams) dissolved in
ethyl alcohol and the resultant mixture placed on a mechanical
roller until the polymeric powder has absorbed the antibiotic. The
solution is then filtered.
The resulting microcapsules of chloramphenical antibiotic are mixed
with 100 grams of a 22 percent solution in heptaneisopropylalcohol
(70:30) of a rubbery 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 10 centimeters
in length and the solvent removed by evaporation.
When applied to the skin of a subject, the resulting bandage is
effective to administer chloramphenicol antibiotic through the skin
to circulation to provide a continuous administration of the daily
dose of the antibiotic.
EXAMPLE II
Liquid dimethyl silicone rubber (100 grams, Dow-Corning Silastic)
is mixed with finely divided crystalline megesterol acetate (5
grams). After uniformly mixing the hormone with the 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.
Five grams of the resulting encapsulated megesterol acetate are
mixed with an elastomeric silicone pressure-sensitive adhesive (10
grams) to uniformly distribute the microcapsules throughout the
adhesive. Immediately thereafter, the adhesive mixture is coated
onto one surface of a 100-square centimeter Mylar sheet. The
resulting bandage is used for fertility regulation.
Thus, this invention provides an easy to use device for
administering systemically active drugs through the skin and oral
mucosa. Uncertainties of administration through the
gastrointestinal tract are avoided and a constant level of drug in
circulation can be obtained. Treatment is begun by applying the
bandage to the skin or oral mucosa and terminated by removing it
therefrom. The bandage can contain and administer the complete
dosage requirements for a particular time period, for example, for
24 hours. Intervention by the patient is required only to apply and
remove the bandage, so that uncertainties are eliminated.
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
bandage 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.
* * * * *