U.S. patent number 3,734,097 [Application Number 05/136,981] was granted by the patent office on 1973-05-22 for therapeutic adhesive tape.
This patent grant is currently assigned to Alza Corporation. Invention is credited to Alejandro Zaffaroni.
United States Patent |
3,734,097 |
Zaffaroni |
* May 22, 1973 |
THERAPEUTIC ADHESIVE TAPE
Abstract
Adhesive laminate tape for the topical administration of
controlled therapeutically effective quantities of drug selected
from the group consisting of anti-neoplastic agents, folic acid
antagonists and anit-mitotic agents for the treatment of skin
lesions, comprising a backing member bearing a pressure-sensitive
adhesive, the adhesive having distributed therein a means for
metering the flow of a therapeutically effective amount of the drug
to the lesions over a prolonged period of time.
Inventors: |
Zaffaroni; Alejandro (Atherton,
CA) |
Assignee: |
Alza Corporation (Palo Alto,
CA)
|
[*] Notice: |
The portion of the term of this patent
subsequent to August 10, 1988 has been disclaimed. |
Family
ID: |
27495240 |
Appl.
No.: |
05/136,981 |
Filed: |
April 23, 1971 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
|
|
812116 |
Apr 1, 1969 |
3598122 |
Aug 10, 1971 |
|
|
812117 |
Apr 1, 1969 |
3598123 |
Aug 10, 1971 |
|
|
Current U.S.
Class: |
424/448; 604/304;
424/449 |
Current CPC
Class: |
A61L
15/58 (20130101); A61K 9/7061 (20130101); A61K
9/7053 (20130101); A61K 9/7076 (20130101); A61K
9/7084 (20130101); A61K 9/7092 (20130101); A61F
9/0017 (20130101); A61L 15/44 (20130101); A61M
31/002 (20130101); A61L 2300/432 (20130101); A61L
2300/41 (20130101); A61L 2300/622 (20130101); A61L
2300/602 (20130101); A61L 2300/416 (20130101) |
Current International
Class: |
A61K
9/70 (20060101); A61L 15/44 (20060101); A61L
15/58 (20060101); A61L 15/16 (20060101); A61F
9/00 (20060101); A61M 31/00 (20060101); A61f
007/02 () |
Field of
Search: |
;128/260,268,271,156,296
;424/22,28,56,351 |
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. 812,116, now
U.S. Pat. No. 3,598,122, filed Apr. 1, 1969, entitled "Bandage for
Administering Drugs" and Ser. No. 812,117, filed Apr. 1, 1969,
entitled "Bandage" now U.S. Pat. No. 3,598,123, both applications
of Alejandro Zaffaroni and both issued on Aug. 10, 1971, as U.S.
Pat. Nos. 3,598,122 and 3,598,123 respectively.
Claims
What is claimed is:
1. A therapeutic adhesive tape for the topical administration of
controlled quantities of drug for the treatment of skin lesions,
said tape 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 discreet microcapsules,
each of which microcapsules comprise a therapeutic agent selected
from the group consisting of an anti-neoplastic agent and a folic
acid antagonist 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 therapeutic agent to the skin lesions from the microcapsules
at a controlled and predetermined rate over a period of time.
2. The therapeutic adhesive tape of claim 1 wherein said
microcapsules (3) comprise a matrix of the drug release rate
controlling wall material, said matrix having the therapeutic agent
distributed therethrough.
3. The therapeutic adhesive tape of claim 1 wherein said
microcapsules (3) comprise the therapeutic agent microencapsulated
within the drug release rate controlling wall material.
4. The therapeutic adhesive tape of claim 1 wherein said folic acid
antagonist is selected from the group consisting of methotrexate,
aminopterin, 3'-chloromethotrexate and 3',
5'-dichloromethotrexate.
5. The therapeutic adhesive tape of claim 1 wherein said
anti-neoplastic agent is selected from the group consisting of
vincristine, vinblastine, 5-fluorouracil, 5-fluorodeoxyuridine and
6-mercotopurine.
6. The therapeutic adhesive tape of claim 1 wherein said
therapeutic agent is methotrexate present at a concentration of
0.01 to 100 micrograms of methotrexate per sq. cm. of surface of
pressure-sensitive adhesive coating.
7. The therapeutic adhesive tape of claim 1 further containing an
anti-inflammatory steroid.
8. A therapeutic adhesive tape for the topical administration of
controlled quantities of drug for the treatment of skin lesions,
said tape comprising a laminate of (1) a backing member; (2) a
discrete middle reservoir layer containing a therapeutic agent
selected from the group consisting of an anti-neoplastic agent and
a folic acid antagonist 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 therapeutic agent to the skin lesions 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.
9. The therapeutic adhesive tape of claim 8 where the reservoir
layer (2) comprises a walled container having an interior chamber
containing the therapeutic agent.
10. The therapeutic adhesive tape of claim 8 wherein the reservoir
layer (2) comprises a matrix of the drug release rate controlling
wall material, said matrix having the therapeutic agent distributed
therethrough.
11. The therapeutic adhesive tape of claim 8 further including a
solubility membrane interposed between said reservoir and said
pressure-sensitive adhesive coating.
12. The therapeutic adhesive tape of claim 8 wherein said folic
acid antagonist is selected from the group consisting of
methotrexate, aminopterine, 3'-chloromethotrexate and 3',
5'-dichloromethotrexate.
13. The pressure-sensitive adhesive tape of claim 8 wherein said
anti-neoplastic agent is selected from the group consisting of
vincristine, vinblastine, 5-fluorouracil, 5-fluorodexyuridine, and
6-mercoptopurine.
14. The therapeutic adhesive tape of claim 8 wherein said
therapeutic agent is methotrexate.
15. The therapeutic adhesive tape of claim 8 wherein said
therapeutic agent is methotrexate present at a concentration of
0.01 to 100 micrograms of methotrexate per sq. cm. of surface of
pressure-sensitive adhesive coating.
16. The therapeutic adhesive tape of claim 8 further including an
anti-inflammatory steroid.
Description
BACKGROUND OF THE INVENTION
This invention relates to a therapeutic adhesive tape and more
especially, to a therapeutic adhesive tape for the treatment of
skin lesions, such as psoriatic lesions.
Severe skin lesions, such as psoriatic lesions, are conventionally
treated with anti-inflammatory steroids administered systemically
or topically. With systemic administration of anti-inflammatory
steroids, as by injection or through the gastrointenstinal tract,
severe side-effects have been reported. These include death,
steroid-induced diabetes, severe bacterial infection, severe
osteoporosis, severe cutaneous atrophy, myopathy, pituitary
failure, and others. While these side-effects are generally not
experienced with topical steroid therapy, many severe skin lesions,
including many psoriatic lesions, do not respond favorably to
topical steroid therapy. As a result, the medical profession has
looked to alternative therapeutic regimes for the treatment of skin
lesions.
It has long been recognized that many skin lesions, including
psoriatic lesions, are caused by rapid or run-away growth of skin
cells. To slow the cell growth rate to a more normal one, treatment
with various anti-metabolites has been proposed. Severe cases of
psoriasis have been effectively treated by systemic administration
of folic acid antagonists, such as methotrexate, and by
anti-neoplastic agents, such as 5-fluorouracil. However, when
administering these agents systemically, massive doses must be
employed and this has led to some significant toxic side-effects.
Although these agents have also been found to be topically active
in the treatment of severe skin lesions, substantial problems have
been encountered in their effective topical application. Due
perhaps to instability of the compounds themselves and their
instability or unavailability from creams and solutions, many
studies using topical creams and ointments containing these agents
have been found them to be topically inactive in the treatment of
skin lesions. There is a significant need for a reliable
preparation for the topical application of folic acid antagonists
and anti-neoplastic agents in the treatment of severe skin
lesions.
SUMMARY OF THE INVENTION
Accordingly, one object of this invention is to provide a dosage
unit for the topical treatment of severe skin lesions, such as
psoriatic lesions.
Another object of this invention is to provide a stable, topical
preparation for reliably applying folic acid antagnosists or
anti-neoplastic agents to severe skin lesions in a convenient and
sanitary manner.
In accomplishing these objects, one feature of this invention
resides in a therapeutic adhesive tape for treatment of skin
lesions by direct application to the skin lesions. The tape has a
backing member and a surface having a pressure-sensitive adhesive
coating, the tape containing an amount of a therapeutic agent
selected from an anti-neoplastic agent and a folic acid antagonist
sufficient to release a therapeutically effective amount of the
therapeutic agent to the skin lesions.
Another feature of this invention resides in a therapeutic adhesive
tape as described above wherein the anti-neoplastic agent or folic
acid antagonist is uniformly distributed throughout the
pressure-sensitive adhesive coating.
Still another feature of this invention resides in a therapeutic
adhesive tape as described above wherein the anti-neoplastic agent
or folic acid antagonist is encapsulated with a material permeable
to passage of the therapeutic agent and the microcapsules are
uniformly distributed throughout the pressure-sensitive
adhesive.
A further feature of this invention resides in an adhesive tape as
described above wherein the backing member has on one surface
thereof a reservoir containing the anti-neoplastic agent or folic
acid antagonist and permeable to passage of those therapeutic
agents, 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
treatment of skin lesions, such as psoriatic lesions, by directly
applying to the lesions an adhesive tape releasing a
therapeutically effective amount of an anti-neoplastic agent or
folic acid antagonist to the lesions.
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 tape of
the invention having the folic acid antagonist or anti-neoplastic
agent uniformly distributed throughout the pressure-sensitive
adhesive coating;
FIG. 2 is a cross-sectional view of a modified adhesive tape of the
invention wherein the folic acid antagonist or anti-neoplastic
agent is microencapsulated with a material permeable to passage of
those therapeutic agents and the microcapsules are uniformly
distributed throughout the pressure-sensitive adhesive coating;
FIG. 3 is a cross-sectional view of another embodiment of the
invention wherein the anti-neoplastic agent or folic acid
antagonist is uniformly distributed throughout a matrix laminated
to the backing member and bearing a coating of the
pressure-sensitive adhesive;
FIG. 4 is a cross-sectional view of another embodiment of the
invention wherein a solubility membrane is interposed between the
reservoir layer and the pressure-sensitive adhesive coating;
and
FIG. 5 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 folic acid
antagonist or anti-neoplastic agent 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 tape containing an anti-neoplastic agent or folic acid
antagonist.
As illustrated in FIG. 1, the adhesive tape 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 anti-neoplastic agent or folic acid antagonist. Folic acid
antagonists suitable for use in the adhesive tape of the invention
include methotrexate, aminopterin, 3'-chloromethotrexate and 3',
5'-dichloromethotrexate, with methotrexate being the preferred
folic acid antagonist. Anti-neoplastic agents for use in the
invention include vincristine, vinblastine, 5-fluorouracil,
5-fluorodeoxyuridine, and 6-mercaptopurine, with use of
5-fluorouracil being preferred. Antimitotic agents, such as
colchicine and podophyllum, can also be used alone or in
conjunction with the folic acid antagonist or anti-neoplastic agent
to enhance their properties. In addition to the aforementioned
compounds, simple pharmacologically acceptable derivatives of the
drugs, such as ethers, esters, amides, acetals, salts, etc., having
the desired skin penetration and stability properties can be
prepared and used in practicing the invention. Drugs mentioned
above can be used alone or in combination with each other.
Anti-neoplastic agent or folic acid antagonist is incorporated in
the adhesive tape in an amount sufficient to release a
therapeutically effective amount of the drug to skin lesions to
which applied. Usually, the drug is incorporated in the adhesive
tape in a concentration of 0.01 to 100 micrograms of drug per
square centimeter of surface of the pressure-sensitive adhesive
coating. However, with some drugs such as 5-fluorodeoxyuridine and
podophyllum, the concentration can range as high as 1,000
micrograms per sq. cm. There is no benefit in exceeding these
limits.
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 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 silicon 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 occlusive and non-occlusive, flexible or non-flexible
backing members can be used in the adhesive tape 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 absorption of the folic acid antagonist or
anti-neoplastic agent by the skin.
To prepare the therapeutic adhesive tape, an anti-neoplastic agent
or folic acid antagonist 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 anti-neoplastic
agent or folic acid antagonist can be sprayed on the adhesive
surface of the tape, one of whose sides is already coated with the
pressure-sensitive adhesive.
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 tape of the invention, it is applied directly
to skin lesions, to release a therapeutically effective amount of
the anti-neoplastic agent or folic acid antagonist to the lesion.
By use of this invention, one ensures that an accurately measured
quantity of the active drug is available when the adhesive tape is
applied to the lesion, since the drug is uniformly distributed over
the pressure-sensitive adhesive face surface of the tape. The tape
is effective to maintain the active agent in contact with the
lesion and to enhance subcutaneous penetration of the drug.
Uncertainties previously encountered in application of these agents
from creams or ointments are avoided and a reliable, stable topical
preparation is provided.
FIG. 2 illustrates a modified adhesive tape 20 of the invention
including a backing member 21 bearing a pressure-sensitive adhesive
coating 22 on one surface thereof. Adhesive coating 22 has
uniformly distributed therethrough microcapsules 23 of folic acid
antagonist or anti-neoplastic 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, 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 tape. 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, silicon 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, 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 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 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 a 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 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 tape.
Further embodiments of the therapeutic adhesive tape of the
invention are illustrated in FIGS. 3,4 and 5. As illustrated in
FIG. 3, the adhesive tape 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 folic
acid antagonist or anti-neoplastic agent 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, as by diffusion, to gradually release drug to
adhesive layer 33 over a prolonged period of time.
FIG. 4 illustrates a further modified form of the invention in
which a solubility membrane 35 is interposed between reservoir 32
and pressure-sensitive adhesive layer 33.
FIG. 5 illustrates a further form of the therapeutic adhesive tape
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 folic acid antagonist or anti-neoplastic agent 44.
Wall 45 of reservoir 42, remote from backing member 41, is
permeable to passage of drug 44, as by diffusion, to meter the flow
of drug to pressure-sensitive adhesive layer 46 on the outer
surface thereof. This form of the therapeutic adhesive tape 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 lesions.
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; or by immersing the solid matrix in the
drug to effect diffusion of the drug into the matrix.
Thus, the reservoir of the therapeutic adhesive tape 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 lesion to which the therapeutic adhesive tape 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, as with the walls of the
reservoir, usually 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.
The following examples will serve to illustrate the invention
without in any way being limiting thereon.
Example 1
Pressure-sensitive adhesive composition is prepared by adding to
100 milliliters of hexane the following:
20 grams of polyvinylethyl ether (reduced viscosity=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
To the resulting solution are added 10 milligrams of methotrexate
and the solution stirred for 60 minutes. The resulting methotrexate
containing solution is applied to a 100 by 100 centimeter
polyethylene sheet to a uniform thickness and the solvent removed
by drying to give about 3 milligrams of adhesive per centimeter
square of polyethylene. The methotrexate present in the adhesive
layer is at a concentration of about 1 microgram per square
centimeter. The resulting therapeutic adhesive tape is effective in
the treatment of psoriatic lesions when applied directly to the
lesions. It can be stored for prolonged periods under an inert
atmosphere and is packaged between hermetically sealed polyethylene
terephthalate sheets prior to use.
Example 2
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
catalylic 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.
To the resulting solution are added 32 milligrams of 5-fluorouracil
and the solution is coated onto a polyvinylchloride sheet. After
removing the solvent by evaporation, it is found that the sheet has
an adhesive coating of a thickness of about 0.05 millimeter and
contains about 4 micrograms of 5-fluorouracil per square centimeter
of adhesive face surface.
Example 3
To 100 milliliter of solvent naptha are added the following
components of a pressure-sensitive adhesive formulation: 15 grams
polyisobutylene having approximate average molecular weight of
about 80,000; 2 grams polyisobutylene having average molecular
weight approximately 10,000; 5 grams hydroabietyl alcohol; 3 grams
fumed silica (SiO.sub.2) and 4 grams mineral oil. 16 milligrams of
aminopterin are added to the resulting solvent naphtha solution
which is then coated onto a rayon acetate cloth sheet. The solvent
free adhesive coating of a thickness of about 0.05 millimeter
contains about 2 micrograms of aminopterin per square centimeter of
adhesive face surface.
Example 4
In a manner similar to that of Example 1, therapeutic adhesive
tapes are prepared containing, respectively, 3'-chloromethotrexate,
3', 5'-dichloromethotrexate, vincristine, vinblastine,
5-fluorodeoxyuridine, and 6-mercaptopurine. These tapes are also
effective in the treatment of skin lesions, such as psoriatic
lesions.
In some instances, it is found that when the therapeutic adhesive
tape is applied, the normal skin surrounding the lesion which makes
contact with the adhesive tape can be slightly inflamed, as
evidence by a reddening of the skin. To prevent such reddening, a
small amount of an anti-inflammatory steroid can be incorporated
into the adhesive tape of the invention. Suitable anti-inflammatory
steroids include cortisone, hydrocortisone, prednisolone, mecrol,
florandrenolone, flumethasone, .beta.-methasone, dexamethasone, and
triamcinolone. When these are employed, they are incorporated in a
concentration of between 0.5 and 10 micrograms of steroid per
square centimeter of pressure-sensitive adhesive face surface.
Normally, the anti-inflammatory steroid is dispersed throughout the
pressure-sensitive adhesive coating regardless of whether the folic
acid antagonist or anti-neoplastic agent is microencapsulated or
incorporated in a reservoir. However, the steroid too can be
microencapsulated or incorporated in the reservoir, in the same
manner as the primary drugs.
Thus, this invention provides a reliable and easy to use device for
administering folic acid antagonists or anti-neoplastic agents
directly to skin lesions. Detrimental side-effects encountered when
these agents are systemically administered are avoided.
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 tape, those skilled in the art will appreciate that the
term "adhesive tape" 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
invention, therefore, to be limited only as indicated by the scope
of the following claims.
* * * * *