U.S. patent number 3,699,963 [Application Number 04/872,862] was granted by the patent office on 1972-10-24 for therapeutic adhesive patch.
This patent grant is currently assigned to ALZA Corporation. Invention is credited to Alejandro Zaffaroni.
United States Patent |
3,699,963 |
Zaffaroni |
October 24, 1972 |
THERAPEUTIC ADHESIVE PATCH
Abstract
Therapeutic adhesive patch for stimulation of uterine
contractions by application to the oral mucosa is comprised of a
backing member, an amount of an oxytocic drug sufficient to release
a therapeutically effective amount of the drug to the oral mucosa,
and a pressure-sensitive adhesive coating. The oxytocic drug can be
dispersed through or coated on the pressure-sensitive adhesive; can
be microencapsulated with a material permeable to passage of the
drug and the microcapsules distributed throughout the
pressure-sensitive adhesive; or can be incorporated in a reservoir
layer permeable to passage of the drug and mounted on or laminated
to the backing member and bearing a coating of the
pressure-sensitive adhesive. The pressure-sensitive adhesive
coating can cover the full-face surface of the adhesive patch or a
part thereof, such as the perimeter of the face surface of the
patch.
Inventors: |
Zaffaroni; Alejandro (Atherton,
CA) |
Assignee: |
ALZA Corporation (N/A)
|
Family
ID: |
25360463 |
Appl.
No.: |
04/872,862 |
Filed: |
October 31, 1969 |
Current U.S.
Class: |
424/435;
604/304 |
Current CPC
Class: |
A61K
9/7069 (20130101); A61K 9/7053 (20130101); A61K
9/006 (20130101) |
Current International
Class: |
A61K
9/00 (20060101); A61K 9/70 (20060101); A61f
007/02 () |
Field of
Search: |
;128/260,268,172,208,222,213 ;424/423 |
References Cited
[Referenced By]
U.S. Patent Documents
Primary Examiner: Michell; Robert W.
Claims
What is claimed is:
1. A therapeutic adhesive patch for the continuous administration
to the oral mucosa of controlled quantities of an oxytocic drug
which is absorbable through the mucosa to stimulate uterine
contractions, said patch comprising a laminate of: (1) a backing
member defining one face surface of the patch; (2) a
pressure-sensitive adhesive adapted for contact with the mucosa,
the external surface of said pressure-sensitive adhesive defining
the other face surface of the patch; (3) at least one reservoir
comprised of an oxytocic drug confined within a wall member and
disposed between the face surfaces defined by (1) and (2); said
wall member being formed from drug release rate controlling
material to continuously meter the flow of a therapeutically
effective amount of drug from the said reservoir to the mucosa at a
controlled and predetermined rate over a period of time.
2. The patch as defined by claim 1 wherein the backing member bears
the pressure sensitive adhesive on one surface thereof and the
reservoir comprises a plurality of discrete microcapsules
distributed throughout the pressure sensitive adhesive.
3. The patch as defined by claim 2 wherein each of said
microcapsule is comprised of an oxytocic drug formulation
microencapsulated with the drug release rate controlling wall
material.
4. The patch as defined by claim 2 wherein each of said
microcapsule is comprised of a matrix of the drug release rate
controlling wall material, said matrix having the oxytocic drug
formulation distributed therethrough.
5. The patch as defined by claim 2 wherein the drug is selected
from the group consisting of oxytocin, desamino-oxytocin, and
pharmaceutically acceptable salts thereof.
6. The therapeutic patch as defined by claim 1 wherein the backing
member bears a discrete, middle reservoir layer, and the
pressure-sensitive adhesive is carried by the surface of the
reservoir layer remote from the backing member.
7. The patch as defined by claim 6, wherein one outer surface of
the wall member comprising the reservoir layer also defines the
backing member.
8. The patch as defined by claim 6 wherein the reservoir layer is
comprised of a walled container having an interior chamber
containing the oxytocic drug.
9. The patch as defined by claim 6 wherein the reservoir layer is
comprised of a matrix of the drug release rate controlling
material, said matrix having the oxytocic drug distributed
therethrough.
10. The patch as defined by claim 6 wherein the drug is selected
from the group consisting of oxytocin, desamino-oxytocin, and
pharmaceutically acceptable salts thereof.
11. The patch as defined by claim 6 wherein the pressure-sensitive
adhesive coating extends only about the perimeter of the surface of
the reservoir.
12. The patch as defined by claim 1 wherein the oxytocic drug is a
pharmaceutically acceptable derivative thereof absorbable through
the oral mucosa.
Description
CROSS REFERENCE TO RELATED PATENTS
This patent is related to U.S. Pat. Nos. 3,598,122 and 3,598,123,
granted Aug. 10, 1971 to Alejandro Zaffaroni.
BACKGROUND OF THE INVENTION
This invention relates to a therapeutic adhesive patch and more
especially, to a therapeutic adhesive patch for administering an
oxytocic drug through the oral mucosa to stimulate uterine
contractions.
Oxytocin, desamino-oxytocin, and other oxytocic drugs are widely
used to stimulate uterine contractions. In general, these drugs are
administered in three types of situations: before the onset of
labor to assess the preparedness of labor; to induce labor; and to
continue labor in patients with primary or secondary uterine
inertia.
Administration of oxytocin by intravenous drip has been found to
give the best control over the rate of drug administration.
However, sometimes large toxic doses are inadvertently administered
by this route. Due to the difficulties of intravenous drip and the
danger that the patient may interfere with the drip rate, oxytocin
and desamino-oxytocin often are administered through the oral
mucosa from buccal tablets. Although most convenient, this route of
drug administration presents many heretofore unsolved problems.
In oxytocin administration, it is vital that the dosage of drug
administered to the patient be precisely controlled during the
full-time course of therapy. Overdosing with oxytocin can cause
severe toxic reactions, including uterine rupture. Good control
over the rate of administration from buccal tablets can not be
obtained due to inability to control the extent to which the
patient will maintain the tablet in contact with the mucosa and to
control or predict the quantity of drug that will dissolve in
saliva and be carried to the gastrointestinal tract.
Another significant problem with buccal tablets is the extremely
long lag-time or latent period between placement of the tablet and
activity in the uterus. This latent period can be on the order of
30 to 40 minutes or more. See Obolensky et al., J. Obstet. Gynaec.
Brit. Cwlth., 76, 245- 251 (March 1969). It is likely that this
delayed activity is due to the slow dissolution of the tablet and
the slow passage of oxytocin through the oral mucosa. This long
latent period makes buccal administration of oxytocin impractical
for use in the second stage of labor and is a severe limitation on
the use of this mode of administration.
In addition to the conventional buccal lozenges or tablets, it has
been suggested to administer oxytocin from buccal tablets designed
to stay in close proximity to the oral mucosa. However, such
tablets have been formed of vehicles soluble in saliva so that
substantial but unpredictable amounts of the drug passed to the
gastrointestinal tract where it would be absorbed. See U.S. Pat.
Nos. 3,429,308 and 3,444,858.
Thus, the problem of developing a dosage form for administering
precisely controlled amounts of rapidly acting oxytocic drugs
through the oral mucosa remains.
SUMMARY OF THE INVENTION
Accordingly, one object of this invention is to provide a dosage
unit for the administration of oxytocic drugs through the oral
mucosa without the disadvantages inherent in previously proposed
forms.
Another object of this invention is to provide a dosage unit for
administering precisely controlled amounts of oxytocic drugs
through the oral mucosa by maintaining the drug in close contact
with the oral mucosa but out of contact with salivary
excretions.
Still a further object of this invention is to provide a dosage
unit for administering oxytocic drugs through the oral mucosa in a
manner so that the drug rapidly acts on the uterus.
In accomplishing these objects, one feature of this invention
resides in a therapeutic adhesive patch for application to the oral
mucosa to stimulate uterine contractions. The patch has a backing
member and a surface having a pressure-sensitive adhesive coating,
the patch containing an amount of an oxytocic drug absorbable
through the oral mucosa sufficient to release a therapeutically
effective amount of the drug to the oral mucosa.
Another feature of this invention resides in a therapeutic adhesive
patch as described above wherein the oxytocic drug is distributed
throughout the pressure-sensitive adhesive coating.
Still another feature of this invention resides in a therapeutic
adhesive patch as described above wherein the oxytocic drug is
encapsulated with a material permeable to passage of the drug and
the microcapsules are distributed throughout the pressure-sensitive
adhesive.
A further feature of this invention resides in a therapeutic patch
as described above wherein the backing member has on one surface
thereof a reservoir containing the oxytocic drug and permeable to
passage of the drug, the reservoir bearing on its surface remote
from the backing member a coating of the pressure-sensitive
adhesive.
Still a further feature of this invention resides in a method for
stimulating uterine contractions by applying to the oral mucosa an
adhesive patch releasing a therapeutically effective amount of an
oxytocic drug absorbable through the oral mucosa.
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 therapeutic adhesive patch of
the invention having the oxytocic drug distributed throughout the
pressure-sensitive adhesive coating;
FIG. 2 is a cross-sectional view of a modified adhesive patch of
the invention wherein the oxytocic drug is micro-encapsulated with
a material permeable to passage of the drug and the microcapsules
are distributed throughout the pressure-sensitive adhesive
coating;
FIG. 3 is a cross-sectional view of another embodiment of the
invention wherein the oxytocic drug is distributed throughout a
matrix laminated to the backing member and bearing a coating of the
pressure-sensitive adhesive; and
FIG. 4 is a cross-sectional view of still another embodiment of the
invention wherein the reservoir laminated to the backing member is
a hollow container permeable to passage of the oxytocic drug and
having the drug within an interior chamber thereof.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with this invention, there is provided a therapeutic
adhesive patch containing an oxytocic drug absorbable through the
oral mucosa.
As illustrated in FIG. 1, the adhesive patch 10 of the invention
has a backing member 11 bearing a pressure-sensitive adhesive
coating 12. Dispersed throughout pressure-sensitive adhesive
coating 12 is an oxytocic drug absorbable through the oral mucosa.
Oxytocic drugs suitable for use in the adhesive patch of the
invention include oxytocin, desamino-oxytocin and others. Oxytocic
drugs which do not pass through the oral mucosa can be used in the
form of simple pharmacologically acceptable derivatives such as
ethers, esters, amides, etc., having the desired absorption
property. Of course, such derivatives should be such as to easily
convert to the active drugs within the body through the action of
body enzyme assisted transformations, pH, etc. In addition to the
drug compounds themselves, their pharmaceutically acceptable salts
can be used. Exemplary salts include, without limitation, the
hydrochloride, hydrobromide, hydroiodide, sulphate, sulfamate,
phosphate, maleate, acetate, citrate, oxalate, succinate, benzoate,
tartrate, fumarate, malate, mandelate, ascorbate, etc.
The amount of oxytocic drug incorporated in the adhesive patch to
obtain the desired uterine contractions will vary depending on the
particular drug used, its rate of release from the patch, the
length of time the patch is to remain in place, and the effect to
be achieved. Since these patches are to be used for but a
particular period of time, there is no critical upper limit on the
amount of oxytocic drug incorporated. For when the patch is removed
and disposed of, it makes little difference whether any drug
remains in it. The lower limit will depend on the activity of the
oxytocic drug and its capability of being released from the patch.
Thus, it is not practical to define a range for the therapeutically
effective amount of oxytocic drug incorporated in or released from
these adhesive patches. However, with an adhesive patch containing
oxytocin, typically from 20 to 200 international units of oxytocin
are incorporated in the patch and the patch is designed to release
the drug at a rate of from 10 to 100 international units per hour.
With adhesive patches containing desamino-oxytocin, from 10 to 100
international units of the drug are incorporated in the patch and
the patch is designed to release the drug at a rate of between 5
and 50 international units per hour. For adhesive patches
containing other oxytocic drugs, the drug is incorporated in and
released from the patch in an amount equivalent in activity to
these ranges.
Any of the well-known orally acceptable pressure-sensitive
adhesives 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, nitrite, 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 flexible or non-flexible backing members can be used in the
adhesive patch of the invention. Suitable backings include
cellophane, cellulose acetate, ethylcellulose, plasticized
vinylacetate-vinylchloride copolymers, polyethylene terephthalate,
nylon, polyethylene, polypropylene, polyvinylidenechloride,
impregnated paper, cloth, and aluminum foil. Preferably, a flexible
occlusive backing is employed to conform to the shape of the oral
mucosa to which the adhesive patch is applied and to enhance
absorption of the oxytocic drug by the mucosa. To avoid leaching of
the oxytocic drug by saliva in use, it is important that the
backing member be substantially impervious to and insoluble in
saliva.
To prepare the therapeutic adhesive patch, an oxytocic drug is
mixed with the pressure-sensitive adhesive and the mixture coated
onto the 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. Alternatively, a solution or
suspension of the drug can be sprayed on the adhesive face surface
of the patch.
To prevent passage of the drug away from the exposed surface of the
pressure-sensitive adhesive prior to use, the adhesive surface of
the patch 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 patch rolled about itself.
To use the adhesive patch of the invention, it is applied to the
oral mucosa, usually to the palate or buccal mucosa, to release a
therapeutically effective amount of the oxytocic drug to the
mucosa. Oxytocic drug within the adhesive patch of the invention
migrates through the pressure-sensitive adhesive layer to the
surface thereof. Ordinarily, one would expect drug migration to
cease when sufficient drug has reached the outer surface of the
adhesive layer to create an equilibrium. However, when the adhesive
layer is in contact with the patient's oral mucosa, drug molecules
are continuously removed from the outer surface of the adhesive
layer and absorbed by the oral mucosa. Absorbed drug molecules pass
through the oral mucosa and enter circulation through the capillary
network.
By use of this invention, one ensures that an accurately measured
quantity of the oxytocic drug is applied to the oral mucosa.
Because the backing member and pressure-sensitive adhesive coating
prevent mingling of the oxytocic drug with saliva, the problem of
transfer of quantities of the drug to the gastrointestinal tract is
avoided. Moreover, the adhesive patch is effective to maintain the
oxytocic drug in contact with the oral mucosa and to enhance
penetration of the drug through the mucosa. This is most important,
as the high concentration of drug at the mucosal surface
significantly decreases the latent period between administration
and stimulation of uterine contractions. This permits use of oral
mucosal administration of oxytocic drugs during the second stage of
labor. Furthermore, the rate of release of oxytocic drug from the
patch of the invention can be accurately measured and controlled.
This avoids the problems of overdosage previously encountered when
oxytocic drugs were administered through the oral mucosa.
FIG. 2 illustrates a modified adhesive patch 20 of the invention
including a backing member 21 bearing a pressure-sensitive adhesive
coating 22 on one surface thereof. Adhesive coating 22 has
distributed therethrough microcapsules 23 of oxytocic drug
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 through the walls of the
microcapsules. 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 walls, 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 adhesive patch. By varying the
encapsulating material and the wall thickness, the dosage rate per
area of patch can be controlled and movement of drug through 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,
styrene-butadiene rubbers, polyisoprene, polybutadiene,
polyisobutylene, and polyethylene terephthalate; and hydrophilic
polymers such as esters of acrylic and metha-crylic 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
polyvinylalcohol, cross-linked partially hydrolyzed
polyvinylacetate, cellulosics such as methylcellulose,
ethylcellulose, and hydroxyethylcellulose, and gums such as acacia,
carboxymethylcellulose, and carageenan alone or combined with
gelatin.
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 acacia, 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 membrane to meter the flow of drug to the
adhesives; use of a matrix and a different 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 FIG. 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 the drug by
immersion in a bath of the drug or drug solution 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 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.
The microcapsules, however made, are then mixed with any of the
previously described pressure-sensitive adhesives and the mixture
coated onto the backing member to provide the therapeutic adhesive
patch.
Further embodiments of the therapeutic adhesive patch of the
invention are illustrated in FIGS. 3 and 4. As illustrated in FIG.
3, the adhesive patch 30 of the invention is comprised of a backing
member 31 having a reservoir 32 on one surface thereof. One wall of
reservoir 32 remote from backing member 31 bears a
pressure-sensitive adhesive coating 33. Reservoir 32 contains
oxytocic drug 34 dispersed therethrough. In the embodiment of FIG.
3, reservoir 32 is a polymeric matrix having the drug distributed
therethrough. It is permeable to passage of drug 34 to release drug
to adhesive layer 33.
FIG. 4 illustrates a further form of the therapeutic adhesive patch
40 including a backing member 41 and a reservoir 42 in the form of
a hollow container having an interior chamber 43 containing
particles of oxytocic drug 44. Wall 45 of reservoir 42, remote from
backing member 41, is permeable to passage of drug 44 to meter the
flow of drug to pressure-sensitive adhesive layer 46 on the outer
surface thereof.
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 contained 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; or by immersing the solid matrix in the
drug or a solution of the drug to effect diffusion of the drug into
the matrix.
Thus, the reservoir of the therapeutic adhesive patch 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, porosity, and thickness of the reservoir or of the
reservoir wall. From the adhesive layer, drug is directly
transmitted to the oral mucosa to which the therapeutic adhesive
patch is applied.
In one form of the invention, the adhesive is applied to the
drug-containing reservoir at the point of use. This avoids
premature saturation of the adhesive with drug and provides further
control over the rate of oxytocic drug administration. To achieve
this, the reservoir, mounted on the backing, is supplied with a
strippable protective film, and the adhesive is supplied in film
form with a strippable protective film on each surface. For use,
the protective film is removed from the reservoir and one surface
of the adhesive, the adhesive applied to the reservoir, and the
remaining protective film removed from the adhesive face surface of
the now assembled patch.
While FIGS. 3 and 4 illustrate the reservoirs 32 and 42 as bearing
a uniform coating of the pressure-sensitive adhesive, this is
unnecessary. Adhesive coating 33 can be disposed about the
perimeter of the face surface of reservoirs 32 and 42 to provide a
liquid-tight seal and to maintain the face surface of reservoirs 32
and 42 in contact with the oral mucosa. In such case, molecules of
oxytocic drug passing through the reservoir are conveyed directly
from the surface of the reservoir to the oral mucosa.
The following examples will serve to illustrate the invention
without in any way being limiting thereon.
EXAMPLE 1
Pressure-sensitive adhesive of the following composition:
Polyisobutylene (Approximate average molecular weight--10,000) 20
gms. Polyisobutylene (Approximate average molecular weight--about
80,000) 5 gms. Carboxymethyl cellulose 2 gms. Pectin 3 gms. Gelatin
15 gms. Polyvinylmethyl ether (100% solids; reduced viscosity of
0.4 to 0.5) 2 gms.
is prepared by callendering the polyisobutylenes at 90.degree. C
and mixing uniformly. Remaining components of the adhesive are then
added to the molten rubbery mass to obtain a homogeneous
composition. Oxytocin is mixed with the adhesive to obtain about 40
international units of drug per square centimeter area of adhesive
having a thickness of 0.5 mm. The adhesive-drug mixture is applied
to a sheet of polyethylene (thickness of 0.5 mil) to a thickness of
0.5 mm. and patches 2 cm. by 2 cm. are cut from the coated
sheet.
Each such patch contains 160 international units of oxytocin. When
applied to the oral mucosa, the pressure-sensitive adhesive forms a
liquid-tight bond which permits rapid migration of oxytocin from
the adhesive to the surface of the mucosa in contact therewith.
This build-up of drug at the surface provides a gradient driving
force for absorption of oxytocin by the mucosa. The polyethylene
backing member is impermeable to oxytocin and liquids in the mouth
so no drug escapes from the patch to be carried to the
gastrointestinal tract. By applying the patch to the oral mucosa,
uterine contractions are stimulated.
EXAMPLE 2
The procedure of Example 1 is repeated except that
desamino-oxytocin is substituted for oxytocin to provide an
adhesive patch containing 80 international units of
desamino-oxytocin.
EXAMPLE 3
Pressure-sensitive adhesive of the following composition:
Polyvinylethyl ether (98% solids; reduced viscosity 0.2 to 0.4 ) 5
gms. Polyvinylethyl ether (98% solids; reduced viscosity 3.5 to
4.5) 10 gms. Polyvinylmethyl ether (97% solids; reduced viscosity
of 0.3 to 0.5) 10 gms. Anionic heteropolysaccharide (Biopolymer
XB--23 made by carbohydrate fermentation by bacterium Xanthomonas
Campestris) 15 gms. Pectin 5 gms. Gum acacia 2 gms.
is prepared by callendering the ethers and then adding the
remaining components with thorough mixing. To this adhesive,
oxytocin is added to provide 30 international units per square
centimeter when the adhesive is coated onto a polyethylene backing
sheet (thickness of 0.5 mil) to a thickness of 0.5 mm. Patches
having a face surface area of 2.25 square centimeters are stamped
from the coated sheet and used to stimulate uterine contractions by
application to the oral mucosa.
EXAMPLE 4
In the same manner as Example 3, adhesive patches are prepared
containing 15 international units of desamino-oxytocin per square
centimeter of face surface.
Thus, this invention provides a reliable and easy to use
drug-delivery system for administering oxytocic drugs through the
oral mucosa. Since the system is maintained in liquid-tight
communication with the oral mucosa, a predetermined dose of drug
can be administered. Uncertainties in rate of administration,
inherent in prior dosage units, are overcome and the substantial
toxic effects of overdosing are avoided. Because the drug is
maintained in contact with the mucosa, the latent period for
activity of the drug after administration is substantially
shortened permitting more widespread usage of this convenient route
of administration.
Although the product of this invention has been referred to as an
adhesive patch, those skilled in the art will appreciate that the
term "adhesive patch" as used herein includes any product having 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 patch 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.
* * * * *