CA2133598C

CA2133598C - Non-occlusive adhesive patch for applying medication to the skin

Info

Publication number: CA2133598C
Application number: CA002133598A
Authority: CA
Inventors: David Rolf; Elisabeth K. Sjoblom Urmann
Original assignee: Lectec Corp
Current assignee: Axogen Inc
Priority date: 1994-03-30
Filing date: 1994-10-04
Publication date: 2002-03-05
Anticipated expiration: 2014-10-04
Also published as: FI950465A; DK0674913T3; US5741510A; EP0674913B1; ES2224102T3; US6096334A; AU1002495A; ATE269744T1; NO951217L; CA2133598A1; DE69433859T2; US5536263A; JPH07265353A; EP0674913A3; EP0674913A2; US6096333A; US6361790B1; DE69433859D1; AU676623B2; NO951217D0

Abstract

A non-occlusive medication patch (32) to be applied to the skin includes a porous self-supporting backing layer (10) to give the patch the required integrity and strength by acting as a supporting framework for other components, and a flexible hydrophilic pressure-sensitive adhesive reservoir (20) comprising a natural or synthetic polymer for the sustained release of medication to be absorbed topically through the skin into the body of a patient. The reservoir has two portions: first, an external coating layer (24) with an exposed lower skin-contacting surface (24b) that forms a pressure-sensitive bond with the skin, and second, an upper internal portion (24a) which infiltrates the porous backing (10) and becomes solidified therein after being applied so that the reservoir and the backing are unified, enabling the backing itself to act as a storage location for the medication-containing reservoir (20). The medication within the reservoir migrates over time from within the backing (10) through the lower coating layer (24b) and passes through the skin to provide sus-tained release of the medication into the body of a patient.

Description

NON-OCCLUSIVE ADHESIVE PATCH FOR
APPLYING MEDICATION TO THE SKIN
FIELD OF THE INVENTION
This invention relates to a non-occlusive adhesive patch for applying medication to the skin.
BACKGROUND OF THE INVENTION
Several kinds of patch devices have been used in the past for applying medication to the skin. For example, U.S.
Patent 4,675,009 describes a drug dispensing device for transdermal delivery of' medication in which a natural or synthetic polysaccharide or synthetic polymer functions as a non-biodegradable adhe~;ive reservoir. These patches, while very good, are so thick and cumbersome that users complain of their appearance and the discomfort associated with their use. Another deficiency is found in analgesic patch products that contain a rubber sheet backing which occludes the skin, making moisture evaporation virtually impossible.
An object of the present invention is to provide a non-occlusive analgesic patch, i.e., one which will enable moisture vapour on the surface of the skin to evaporate through the patch so as to prevent the undesired accumulation of moisture which, if it occurred, could cause the patch to fall off or even facilitate the growth of bacteria beneath the patch. Another objective of the present invention is to provide a much lighter, more flexible and less obtrusive patch while still providing excellent sustained release properties during eight hours or more of use.
SUMMARY OF THE INVENTION
A non-occlusive medication-containing adhesive patch is provided for being applied to the skin for releasing a medication into the body of a patient. The patch has a porous backing layer that can be formed from a fibrous material, e.g., non-woven fabric. To the backing is applied a flexible pressure-sensitive adhesive, typically a hydrocolloidal gel which serves as a reservoir for the sustained release of a medication which is uniformly distributed throughout the adhesive layer. The pressure-sensitive reservoir has two portions including, an external coating layer portion with an exposed surface for bonding to the skin and an internal portion that is infiltrated within the porous backing layer. The adhesive reservoir comprises a natural or synthetic polymer and a biomedically-active medication dispersed therein. The internal portion of the hydrocolloidal reservoir which infiltrates the backing is solidified within the pores and interstices within the backing so that the reservoir and the backing are unified, enabling the backing itself to act as a storage location for the medication-containing reservoir. The gel reservoir is applied as a fluid. Solidification of the gel reservoir is delayed until after the gel has been applied to the porous backing layer.
Briefly, the present invention provides a non-occlusive medication patch to be applied to the skin. It includes a porous self-supporting backing layer to give the patch the required integrity and strength by acting as a supporting framework for other components, and a flexible hydrophilic pressure-sensitive adhesive reservoir comprising a hydrocolloidal gel for the sustained release of medication to be absorbed topically through the skin into the body of a patient. The reservoir has two portions: first, an external coating layer with an exposed lower skin-contacting surface that forms a pressure-sensitive bond with the skin, and second, an upper internal portion which infiltrates the porous backing and becomes solidified therein after being applied so that the reservoir and the backing are unified, enabling the backing itself to act as a storage location for the medication-containing reservoir. In this way, the medication within the reservoir migrates over time from within the backing through the lower coating layer and passes through the skin to provide sustained release of the medication into the body of a patient.
The reservoir comprises a hydrocolloidal dispersion of a natural or synthetic gel-forming polymer, a hydrophilic adhesive, a hydrophilic humectant and a biomedically-active -2a-medication, i.e., a medicament, dispersed throughout the reservoir including both the external portion and the internal portion that infiltrates the porous backing.
The invention provides a comfortable, highly flexible patch that is thinner than prior patches, conforms to the body contours, is better tolerated by patients, and is considered by patients to be more unobtrusive. The invention provides outstanding results as a non-occlusive analgesic patch that can be adhered to the skin to release an analgesic for the relief of pain including arthritis pain, backache as well as muscular aches and strains. In such an application, the analgesic comprises trolamine salicylate, menthol salicylate, menthol, camphor, eucalyptus oil or spearmint oil, or a combination thereof.
In another aspect the invention provides a method of forming a non-occlusive medication-containing adhesive patch to be applied to the skin for releasing a medication into the body of a patient. They method comprises providing a porous backing layer of flexible water-insoluble polymeric sheet material, forming a dispersion of a polymer comprising an adhesive and a biomedic:ally-active medication to provide a pressure-sensitive hydrocolloidal gel reservoir, and expelling the hydrocolloidal gel onto the backing layer. The hydrocolloidal gel is f=ormed into a coating on the backing;
the coating having a flat, exposed, pressure-sensitive surface for bonding to the skin. The pressure-sensitive -2b-hydrocolloidal gel reservoir thereby has two portions; an external coating layer with its exposed surface for bonding to the skin, and an inf=ernal portion infiltrated within the pores of the backing layer. The hydrocolloidal gel is allowed to cure in pla<:e upon and within the porous backing layer.
The invention wil_L be better understood by reference to the following specification and accompanying drawings.
THE FIGURES
Figure 1 is a perspective diagrammatic view illustrating a preferred method of forming products in accordance with the invention;
Figure 2 is a perspective view of the improved medication patch applied to the body;
Figure 3 is a plan view showing the medication patch packaged within in a pouch used as a shipping package;
Figure 4 is a cross-sectional view of the medication patch taken on line 4-4 of Fig. 3 with a portion of the liner sheet partially removed; and Figure 5 is a greatly enlarged microscopic view of the medication patch and liner sheet taken on line 5-5 of Fig. 4.
-2c-~i ~~a~8 DETAILED. DESCRIPTION OF THE INVENTION
Refer now to Fig. 1 which illustrates diagrammatically the production of medication-applying patches in accordance with the invention. The backing sheet 10 is unwound continuously from a supply roll 12, passes upwardly in the figure over an idler roll 14 and then travels horizontally beneath a continuous processing mixer 16 where freshly prepared fluid hydrogel material at 20 is applied to the upper surface of the backing sheet 10.
The backing 10 is a porous self-supporting sheet of water insoluble polymeric material that provides strength and integrity for the adhesive patch as well as acting as a substrate for receiving and retaining a portion of the liquid hydrogel as will be described below.
One preferred backing sheet 10 is a lightweight, pliable strip composed, for example, from a nonwoven fabric which consists of polymeric fibers such as polyester, cotton or cellulose fibers bonded together with a sizing resin. The backing sheet 10 should be nonirritating to human skin. If desired, the backing sheet 10 can be coated on its back surface with a release coating such as a silicone release coating as described in patent 4,696,854 One suitable release coating is a 100% solids electron beam curable silicone such as Tego~ Resin Acrylates/RC-series RC 705 and RC 7~6 by Goldschmidt Chemical Corporation of Hopewell, Virginia. The preferred backing sheet 10 is a porous polymeric water insoluble nonwoven fibrous fabric. A suitable sizing material for bonding the fibres together is a latex resin.
The hacking sheet 10 can comprise other stable, water insoluble flexible sheet materials. One preferred backing comprises a 0.14 mm strip of nonwoven fabric formed from a mixture of cellulose fibers derived from wood pulp and polyester fibers. The fibers are assembled loosely into the backing to maintain porosity. A unifying or sizing resin is applied to hold the fibers together. The sizing resin can comprise a nonirritating resin applied as a latex emulsion. One example is Hycar~ 26477, a resin produced by B.F. Goodrich Co. of Brecksville, Ohio. Another suitable backing sheet is a nonwoven fabric comprising a wetlay cellulose and polyester nonwoven fabric containing as a sizing an acrylic latex emulsion resin, e.g., product number N7601 by Dexter Corporation of Windsor Locks, Connecticut.

~133~~8 In another embodiment of the invention, the backing sheet 10 comprises a porous woven 0.12 mm acetate polymer cloth sometimes known as "silk cloth." Another form of backing sheet 10 is an open-cell plastic foam strip of low density polyethylene or polyvinyl acetate resin. Other backing sheets that can be used include woven cotton cloth or other cloth formed from a synthetic polymer. Suitable synthetic cloths include nylon, polyester, polyacetate.
When the backing sheet 10 is a woven cloth, no sizing resin is needed. The backing sheet 10 is pervious to air so that the patch is non-occlusive to the skin.
The porosity of the backing sheet 10 is important because it provides openings for receiving the hydro-colloidal medication-containing reservoir and it helps to assure that the patch is non-occlusive to the skin. The infusion of the pressure-sensitive hydrocolloidal medication-containing reservoir into the backing sheet 10 is accomplished by controlling manufacturing parameters so as to keep the hydrocolloid sufficiently fluid to prenetrate the backing sheet 10 in spite of its tendency to thicken rapidly when applied. In order to prevent the ~1~3~9~
consistency of the hydrogel from building too fast, i.e.., becoming too viscous to properly penetrate the backing sheet 10, a continuous processing mixer 16 (Fig. 1) which includes rotating auger 18 is chilled to help remove heat produced during mixing and keep the hydrogel cool until applied to the backing 10. This can be accomplished by providing the processing mixer 16 with a cooling jacket through which a coolant such as a chilled mixture of water and ethylene glycol is passed during operation. The components of the hydrogel are continuously added to the mixer 16 during operation. While any suitable mixer 16 can be used, one suitable mixer is a 12.7 cm continuous processing mixer manufactured by Teledyne Readco Company of York, Pennsylvania. The coolant passed through the processing mixer 16 can be maintained at about 0°C. The temperature of the fluid hydrogel 20 as it flows onto the exposed surface of the backing sheet 10 is important for controlling the infiltration of the coating into the backing sheet 10. The coolant will, under typical operating conditions, keep the extruded hydrogel 20 at a temperature of about 9°C to 14°C as it comes into contact with the backing 10. If deeper penetration is desired, the temperature of the hydrogel is lowered to about 9°C for a ~133~~~
typical hydrogel formulation. If less penetration is wanted, the temperature is raised~closer to 15°C.
The hydrogel produced by the processing mixer i6, which is in a chilled fluid condition, is expelled at 20 onto the exposed upper surface of the backing sheet 10 adjacent to a knife blade 22 of a knife coater which is held in spaced relationship above a rotatable support roll 23. The distance between the knife 22 and the roll 23 is controlled in any suitable manner, as by means of adjust-ment screws (not shown) or, if desired, the desired gap or spacing between the knife 22 and roll 23 can be preset to accommodate the backing sheet 10 and the thickness of the hydrogel coating 24 that is being applied to the exposed surface of the backing sheet 10.
In accordance with the invention, the medication-containing hydrogel 20 is applied so as to penetrate a substantial portion of the backing sheet 10, e.g., typically between one-fourth to nine-tenths the thickness of the backing sheet 10. The penetration of the coating 24 into the backing 10 can be seen in Fig. 5. In this case the hydrogel coating 24 has penetrated about three-fourths of the way through the backing sheet 10 to provide an upper, i.e., internal layer 24a of hydrocolloidal material ~I33~98 within the pores between the fibers making up the porous backing sheet 10. The hydrogel material thus includes two layers as seen in Fig. 5; the external coating layer 24 with an exposed pressure-sensitive surface 24b and the upper internal portion 24a which infiltrates and becomes solidified within the backing. in the interstices between the fibers that make up the porous backing sheet 10.
In one product with very good characteristics the backing sheet 10 is 0.14 mm in thickness and the external part of the coating layer 24 is 0.2 mm in thickness to provide a combined thickness for the patch when applied to the body of 0.34 mm. The external hydrogel layer 24 is purposely maintained relatively thin. The hydrocolloidal adhesive reservoir infiltrates into the backing to a depth of about 0.05 mm to 0.13 mm to provide a total hydrocolloid layer, including both the internal and external portions, of about 0.25 mm to 0.33 mm. Because of its thickness, the medication-containing reservoir provides a very adequate supply of medication to assure sustained release of the medication over an extended period of time, e.g., six to eight hours or more. During use, the medication in the internal reservoir portion 24a stored within the backing sheet 10 migrates from within the backing sheet 10 through _g_ ~~~~~98 the external coating layer 24 and then passes through the skin to provide sustained release of the medication into the body of the patient.
After the hydrogel layer 24 is applied to the backing 10, the backing sheet continues moving toward the right as seen in Fig. 1 into close proximity with an oven or heater, in this case a radiant electric heater 25 which radiates heat onto the hydrogel coating layer 24, raising its temperature to about 60°C and causing it to cure, i.e., to set up as a solid that is sufficiently stable to maintain its own shape and resist flow during storage or use. Once the heater 25 has warmed the hydrogel coating 24, it will be solidified and dimensionally stable. If curing is conducted without the application of heat, e.g., at room temperature, it will take longer than when heat is used. A
liner sheet 26 such as polyethylene coated paper is then applied continuously by pressing it onto the exposed surface of the hydrogel layer 24 as the liner sheet 26 passes beneath a rotating roll 28. The assembled laminate 34 then moves further toward the right in the figure where a die press 30 stamps separate patches 32 from the sheet material.

.

21~35~~
The hydrogel 2Q, 24 comprises a hydrocolloidal dispersion of a hydrophilic natural or synthetic gel-forming polymer, a hydrophilic humectant, a biomedically active substance or medication, i.e., a medicament, and a hydrophilic adhesive substance such as an aqueous dispersion of an acrylic adhesive.
The polymer can comprise a natural gum such as gum karaya, gum acacia, locust bean gum, guar gum, or other polysaccharide as well as synthetically formulated poly-saccharides, e.g., modified guar gum, maltodextrin, or celluloses such as carboxymethyl cellulose and carboxy-propyl cellulose. The polymer can also comprise a synthetic polymer such as polyacrylamide and its cogeners or polyacrylic acid. Polyacrylamide is sold under the trademark Polytec 31x by Tecna Corp., Belleville, New Jersey.
The humectant can comprise a polyhydric alcohol such as glycerol, propylene glycol, ethylene glycol, or sorbitol.
The adhesive can comprise any suitable biocompatible hydrophilic adhesive such as a resin emulsion adhesive, e.g.; an acrylate emulsion adhesive or a copolymer of vinyl acetate and dioctyl maleate. The most outstanding results ~13~~98 have been achieved with an acrylic emulsion adhesive. .
Other hydrophilic adhesives that can be used include an acrylic ester copolymer and a vinyl acetate resin.
Any of a variety of topical medications can be used in accordance with the present invention. The medications can be selected from a topical analgesic, anti-pruritic agent, anti-inflammatory agent, anesthetic agent, keratolytic agent and rubrefacient agent. When the patch is used as an analgesic, the analgesic can include trolamine salicylate, methyl salicylate, menthol, camphor, eucalyptus oil, spearmint oil, or a combination thereof. In other applications, the medication can include anti-pruritic agents or anti-inflammatory agent such as hydrocortisone, or anesthetic agents such as benzocaine or lidocaine. Also included are non-steroidal anti-inflammatory agents such as ibuprofen, especially the S-iosmer of ibuprofen. Other medications that can be used include keratolytic agents such as salicylic acid, and rubrefacient agents such as capsicum.
In Fig. 2 the finished patch 32 is seen applied to the surface of the body with the backing 10 exposed and the pressure-sensitive hydrogel layer 24 bonded to the skin.

~~83~98 In Fig. 3 is shown a package containing the finished patch 32 as it appears during shipment and storage. The package 36 comprises a pouch including lower and upper layers of paper 35, 37 or other suitable packaging material such as metal foil coated paper which is sealed to itself along its edges, e.g., at 36a, 36b to provide a sealed pouch containing the finished patch 32.
As shown in Figs. 4 and 5, the finished patch 32 includes the porous backing 10, the hydrogel coating including the lower, i.e., external hydrogel coating layer 24 and the upper or internal portion 24a that permeates the backing 10. The upper surface 26a of the liner sheet 26 is a release surface for facilitating its removal. Before use, the liner sheet 26 is removed by pulling it off the patch as shown at the right in Fig. 4 to expose the pressure-sensitive surface of the layer 24 which is then applied to the skin as shown in Fig. 2.
During use, the upper or internal reservoir portion 24a that infiltrates the backing 10 and is solidified therein serves to store the medication within the backing so that the medication migrates over time from its location at 24a within the backing 10 through the external coating layer 24 and then passes through the skin to ~~33598 provide sustained release of the medication into the body of the patient.
The porosity of the backing 10 combined with the water compatibility of the hydrocolloidal dispersion also makes the patch non-occlusive so that moisture from the body can evaporate through the patch into the atmosphere. The moisture vapor transmission rate (MYTR) of the skin alone under various conditions is typically from about 70 to about 149 g/m2/24hr while the medication applying patch of the present invention is about 612 to 1952 g/m2/24hr. This shows that the invention is non-occlusive because in a given period of time about 8 to 14 times more moisture vapor is transmitted through the patch of the present invention than through the skin. Prior medication-applying patches that employed a rubber backing allow virtually no moisture evaporation from the skin. By contrast, the non-occlusive patch of the present invention will not interfere with moisture evaporation from the skin. This is important because the evaporation of moisture from the skin helps the skin to act in its normal capacity as a barrier to externally applied compounds which, if absorbed in excessive amounts, can produce toxic reactions or skin ~~33~9~
irritation. The invention thus enables the barrier function of the stratum corneum to be maintained.
When used as an analgesic patch, the present invention provides outstanding results in relieving pain such as arthritis pain and backache pain, as well as muscular aches and strains. Because of the thinness of the patch, it is perceived as being more comfortable, more flexible, less obtrusive and is more acceptable to the patient. The backing 10 is rendered so translucent by infiltration of the hydrocolloidal gel that the patch is very inconspicuous on the skin. The entire thickness of the analgesic patch is about 0.34 mm.
The invention will be better understood by reference to the following examples:

z~~~~~~
EXAMPLES
ExamplePercentageComponent Example PercentageComponent Numberby Weight Number by Weight 1 31.8 Glycerin 7 29 Glycerin 0.2 Quatemium-15~ 16 Polytec 31x5 21 Propylene Glycol 30 Propylene Glycol 1 Hydrocortisone 1 Hydrocortisone 25 Karaya 12 Lodexs 21 HB Fuller 3120z2 4 H20 (deionized) 8 HB Fuller 3120z2 2 31.8 Glycerin 0.2 Quatemium-15~ 8 30.8 Glycerin 21.5 Propylene Glycol 15.4 Polytec 31x5 0.5 Hydrocortisone 22.8 Propylene Glycol 25 Karaya 8 Lidocaine 21 BF Goodrich 12 Lodexs Z
d o 3 27.72 Glycerin 8 H
B FFu l~
3120z2 0.64 Quatemium-15~

24.5 Propylene Glycol9 30.8 Glycerin 0.5 Hydrocortisone 12 Karaya 24.64 Karaya 6.4 Lodexs 21 BF Goodrich 8 34x4 29.8 Propylene Glycol 4 27.72 Glycerin 1 Capsicum 0.64 Quatemium-15~ 12 Flexcryl1615~

24.64 Propylene Glycol 1 Hydrocortisone 10 30.8 Glycerin 25 Karaya 12 Karaya 21 BF Goodrich 5.4 Lodexs 9 34x4 33 Glycerin 25.8 Propylene Glycol 18 Karaya 12 HB Fuller 3120z2 9 34x4 5 Benzocaine 0.5 Hydrocortisone 21.5 Propylene Glycol11 31.4 Glycerin 18 BF Goodrich 12.6 Karaya 5.2 Lodexs 6 14 Methyl Salicylate 8 34x4 4 Camphor 29.8 Propylene Glycol 6 Menthol 1 Hydrocortisone 76 BF Goodrich 12 HB Fuller 262223 3120z2 213~~9~
ExamplePercentageComponent Example Component Percentage Number by Weight Number by Weight 12 14 Methyl Salicylate19 15.6 Methyl Salicylate 4 Camphor 6.8 Camphor 6 Menthol 4.8 Menthol 38 BF Goodrich 261713 30 BF Goodrich 38 BF Goodrich 264153 43 BF Goodrich 13 14 Methyl Salicylate20 15 Trolamine Salicylate 4 Camphor 10 Menthol 6 Menthol 34 BF Goodrich 45 BF Goodrich 264153 41 BF Goodrich 31 BF Goodrich 262223 21 20.3 Methyl Salicylate 14 17.4 Methyl Salicylate 6.6 Menthol 7.5 Camphor 32.5 BF Goodrich 5.1 Menthol 40.6 BF Goodrich 70 BF Goodrich 264153 22 15 Methyl Salicylate i5 15.6 Methyl Salicylate 10 Menthol 6.8 Camphor 29 BF Goodrich 4.6 Menthol 46 BF Goodrich 25 BF Goodrich 261713 23 23 Karaya 16 19.8 Karaya 34 Glycerin 36.6 Glycerin 11.5 Methyl Salicylate 15.8 Methyl Salicylate 3 Menthol 2 Spearmint Oil 3 Camphor 25.8 HB Fuller 3120z2 1.5 Spearmint Oil 23 Avery AE2598 17 19 Karaya 37 Glycerin 24 22.5 Karaya 16 Methyl Salicylate 36 Glycerin 2 Spearmint Oil 16 Methyl Salicylate 13 BF Goodrich 261713 3 Spearmint Oil 13 BF Goodrich 264153 8 BF Goodrich 14.5 BF Goodrich 18 20 Karaya 37 Glycerin 25 22.5 Karaya 8 Methyl Salicylate 35.9 Glycerin 8 Trolamine Salicylate 11.8 Methyl Salicylate 2 Spearmint Oil 3.1 Camphor 12.5 BF Goodrich 264153 3.1 Menthol 12.5 BF Goodrich 262223 1.6 Spearmint Oil 22 BF Goodrich ~I3~~~8 ExamplePercentageComponent Example PercentageComponent Number by Weight, Number by Weight 26 24 Karaya 32 23.5 Karaya 34 Glycerin 33.5 Glycerin 15 Methyl Salicylate 15.7 Methyl Salicylate 2 Spearmint Oil 2.8 Spearmint Oil 12.5 BF Goodrich 9.1 BF Goodrich 12.5 BF Goodrich 15.4 BF Goodrich 27 21 Karaya 33 22.6 Karaya 38 Glycerin 35.9 Glycerin 15 Methyl Salicylate 6 Methyt Salicylate 2 Spearmint Oil 5.9 Trolamine Salicylate 12 BF Goodrich 3.2 Camphor 12 BF Goodrich 3.2 Menthol 1.5 Spearmint Oil 28 23 Karaya 7.5 BF Goodrich 37.5 Glycerin 14.2 BF Goodrich 43.8 Methyl Salicylate 1.7 Spearmint Oil 34 22 Karaya i2 BF Goodrich 35 Glycerin 12 Aroset 11966 16 Methyl Salicylate 4 Menthol 29 22 Karaya 6 Camphor 36 Glycerin 2 Spearmint Oil 14.2 Methyl Salicylate 9 BF Goodrich 1.8 Spearmint Oil 6 BF Goodrich 3 Camphor 11.5 Aroset 11969 35 20 Karaya 11.5 BF Goodrich 33.8 Glycerin 0.2 Quatemium-15~

30 22 Karaya 16 Methyl Salicylate 35 Glycerin 4 Menthol 12 Methyl Salicylate 6 Camphor 3.2 Methol 1.5 Spearmint Oil 3.2 Camphor 12 BF Goodrich 1.6 Spearmint Oil 6.5 BF Goodrich 1 i Avery AE2598 12 BF Goodrich 36 54 Glycerin 26 Karaya 31 54 Glycerin 5 BF Goodrich 26 Karaya 5 BF Goodrich 10 Flexcryl1615~ 6.7 Menthol 3.3 Eucalyptus 3.3 Eucalyptus Oil Oil 6.7 Menthol 2I335~8 ExamplePercentageComponent Example PercentageComponent Number by Weight Number by Weight_ 37 53 Glycerin 44 49 Glycerin 25 Karaya 26 Karaya 9.5 Flexcryl 1615 15 BF Goodrich 8.4 Menthol 6.7 Menthol 4.1 Eucalyptus Oil 3.3 Eucalyptus Oil 38 46.5 Glycerin 45 48 Glycerin 8.4 Menthol 24.5 Karaya 4.1 Eucalyptus Oil 15 BF Goodrich 26 Karaya 8.4 Menthol 15 Flexcryl 1615 4.1 Eucalyptus Oil 39 16.8 Menthol 46 49.3 Glycerin 8.2 Eucalyptus Oil 23.2 Karaya 25 Avery AE2598 15 BF Goodrich 34 Glycerin 8.4 Menthol 16 Karaya 4.1 Salicylic Acid 40 54 Glycerin 47 50 Glycerin 26 Karaya 25 Karaya 10 BF Goodrich 262223 15 BF Goodrich 6.7 Menthol 6.7 Menthol 3.3 Eucalyptus Oil 3.3 Eucalyptus Oil 41 54 Glycerin 48 47 Glycerin 26 Karaya 20.5 Karaya 10 BF Goodrich 261713 15 BF Goodrich 6.7 Menthol 11.7 Menthol 3.3 Eucalyptus Oil 5.8 Eucalyptus Oil 42 54 Glycerin 49 49.3 Glycerin 31 Karaya 23.2 Karaya 5 Flexcryl 1615 15 BF Goodrich 6.7 Menthol 8.4 Menthol 3.3 Eucalyptus Oil 4.1 Eucalyptus Oil 43 54 Glycerin 50 47 Glycerin 36 Karaya 24.8 Karaya 6.7 Menthol 6.7 Menthol 3.3 Eucalyptus Oil 3.3 Eucalyptus Oil 18.2 Aroset 11969 The following footnotes identify the trademarks and tradenames appearing in the preceding Table of Examples:
Footnotes:
1 Quatemium-15 is a preservative comprising azoniaadamantane chloride by Dow Chemical of Palatine, IL.
2 HB Fuller 3120z is a residual vinyl acetate monomer resin emulsion in water by HB Fuller of Vadnais Heights, MN.
3 BF Goodrich 26171, 26222, 26334 and 26415 are acrylic ester copolymers of anionic emulsion adhesives by BF Goodrich of Brecksville, OH.
4 34x is an anionic polyacrylamide by Tecna Corporation of Belleville, NJ.
Polytec 31x is a non-ionic polyacrylamide by Tecna Corporation of Belleville, NJ.
6 Lodex is a carbohydrate comprising Malto Dextrin by American Maize-Product Company of Hammond, IN.
7 Flexcryl 1615 is an adhesive of vinyl acetate / dioctylmaleate copolymer by Air Products and Chemical Inc of Allentown, PA.
8 Avery AE259 is an acrylic polymer fatex adhesive by Avery Chemical of Mill Hill, PA.
9 Aroset 1196 is an acrylic polymer adhesive by Ashland Chemical of Columbus, OH.
Many variations of the present invention within the scope of the appended claims will be apparent to those skilled in the art once the principles described herein are understood.

Claims

1. A method of forming a non-occlusive medication-containing adhesive patch to be applied to the skin for releasing a medication into the body of a patient, the method comprising:
providing a porous backing layer of flexible water-insoluble polymeric sheet material;
forming a dispersion of a polymer comprising an adhesive and a biomedically-active medication to provide a pressure-sensitive hydrocolloidal gel reservoir;
expelling the hydrocolloidal gel onto the backing layer while maintaining the dispersion in a chilled condition, the hydrocolloidal gel being chilled to a temperature effective to maintain the dispersion sufficiently fluid when applied to the backing layer to penetrate the backing layer to a depth of at least about one-fourth the thickness of the backing layer;
forming the hydrocolloidal gel into a coating on the backing, the coating having a flat, exposed, pressure-sensitive surface for bonding to the skin, the pressure-sensitive hydrocolloidal gel reservoir thereby having two portions including (a) an external coating layer with said exposed surface for bonding to the skin, and (b) an internal portion infiltrated within the pores of the backing layer; and allowing the hydrocolloidal gel to cure in place upon and within the porous backing layer.

2. The method of claim 1, wherein the curing is accelerated by heating the hydrocolloidal gel after the gel has infiltrated into the pores of the backing layer.

3. The method of claim 1 or 2, wherein the coating of the hydrocolloidal gel is formed by a knife coater, to provide said pressure-sensitive surface for bonding to the skin.

4. The method of claim 1, 2, or 3, wherein a sheet of a liner paper is applied to the pressure-sensitive surface of the hydrocolloidal gel coating to protect the same during shipment and storage.

5. The method of any one of claims 1 to 4, wherein the dispersion is formed continuously within a processing mixer, and then is applied as a continuous stream on a moving strip of said backing layer, and wherein a web of liner paper having a release surface is applied continuously to the exposed pressure-sensitive surface of the hydrocolloidal gel coating to protect the coating during shipment and storage, and said adhesive patches are cut therefrom.

6. The method of any one of claims 1 to 5, wherein the hydrocolloidal gel reservoir is infiltrated into the porous backing layer to a depth of between about one-fourth and nine-tenths the thickness of the backing layer and is solidified within the pores of the backing layer to unify the backing layer and the coating, such that the backing layer acts as a storage location for the medication-containing hydrocolloidal gel reservoir.

7. A method for forming a medication-containing adhesive patch to be applied to the skin, the method comprising:
(a) providing a flexible porous backing layer in sheet form to serve as a support for the patch;
(b) applying an adhesive mass to the flexible porous backing layer such that the adhesive mass is supported by the backing layer;
(c) providing said patch with at least one substance selected from the group comprising karaya, spearmint oil, methyl salicylate, trolamine salicylate, camphor, menthol, emulsion adhesive, capsicum and eucalyptus oil;

(d) providing the adhesive mass with an external exposed portion for bonding to the skin of the patient;
(e) controlling the forming of said adhesive patch to keep the adhesive mass sufficiently fluid to penetrate the backing layer, the backing layer acting as a storage location for said substance such that the backing releases the substance for utilization by the patient; and (f) solidifying the adhesive mass within the backing layer.

8. The method of claim 7, wherein the adhesive mass comprises a hydrocolloidal gel having a pressure-sensitive surface for bonding the patch to the skin of the patient, and the hydrocolloidal gel is applied to the porous backing layer by spreading the gel upon a surface thereof to form a coating thereon.

9. The method of claim 8, wherein heat is applied to cure the coating applied to the backing layer.

10. The method of claim 7, 8 or 9, wherein a liner sheet is removably applied to a pressure-sensitive surface of the adhesive mass, to protect the adhesive during shipment and storage.

11. The method of claim 8 or 9, wherein the adhesive mass is formed continuously within a mixer and is applied as a continuous stream on a moving strip of said backing layer, and a web of liner paper having a slippery release surface is applied continuously to an exposed pressure-sensitive surface of the hydrocolloidal gel coating to protect the coating during shipment and storage, and said adhesive patches are cut therefrom.

12. The method of claim 11, wherein the adhesive mass is infiltrated into the porous backing layer to a depth of between about one-fourth and nine-tenths the thickness of the backing layer, and is solidified within the pores of the backing layer to unify the backing layer such that the backing layer acts as a storage location for the adhesive.

13. A non-occlusive medication-containing adhesive patch to be applied to the skin for releasing medication into the body of a patient, the patch comprising:
a porous backing layer comprising flexible sheet of water-insoluble material, to provide support for the patch;
a flexible hydrophilic pressure-sensitive adhesive hydrocolloidal gel matrix including a natural or synthetic polymer and a biomedically-active substance, the matrix providing a reservoir for the sustained release of the biomedically-active substance to be absorbed through the skin into the body of the patient; and wherein said hydrocolloidal gel matrix penetrates a lower portion of the backing layer, the backing layer has an upper portion that is unpenetrated by the gel matrix, and the gel matrix is solidified within the lower portion of the backing layer and is dimensionally stable whereby the gel matrix partially penetrates the backing layer and leaves the upper portion of the backing layer free from the gel;
said gel matrix having two portions including (a) an external layer with an exposed surface for bonding to the skin, and (b) an internal portion infiltrated within only the lower portion of the porous backing layer;
said backing layer having an upper surface that is spaced-apart from the gel matrix; and said biomedically-active substance being dispersed in the hydrocolloidal gel matrix including said internal portion whereby during use the gel matrix releases the biomedically-active substance through an exposed surface thereof that is bonded to the skin of the patient.

14. The adhesive patch of claim 13, wherein the porous backing layer is a nonwoven fabric comprising water-insoluble polymeric fibers with spaces therebetween.

15. The adhesive patch of claim 14, wherein the nonwoven fabric comprises a mixture of polyester fibers and cotton fibers.

16. The adhesive patch of claim 13, 14 or 15, wherein the matrix comprises a natural or synthetic gel-forming polymer comprising a member selected from the group consisting of gum karaya, gum acacia, locust bean gum, guar gum, modified guar gum, maltodextrin, carboxymethyl cellulose, carboxypropyl cellulose, polyacrylamide and its cogeners, and polyacrylic acid.

17. The adhesive patch of any one of claims 13 to 16, wherein the gel matrix includes a humectant that comprises a polyhydric alcohol.

18. The adhesive patch of claim 17, wherein the polyhydric alcohol comprises a member selected from the group consisting of glycerol, propylene glycol, ethylene glycol and sorbitol.

19. The patch of claim 17, wherein the polyhydric alcohol is selected from the group consisting of glycerin and propylene glycol.

20. The adhesive patch of any one of claims 13 to 19, wherein the gel matrix includes a resin emulsion adhesive.

21. The adhesive patch of claim 20, wherein the resin emulsion adhesive comprises a member selected from the group consisting of acrylate emulsion adhesive, an acrylic ester copolymer, a vinyl acetate resin, and a copolymer of vinyl acetate and dioctyl maleate.

22. The adhesive patch of any one of claims 1 to 21, wherein said biomedically-active substance comprises at least one of the following: a topical analgesic, an anti-pruritic agent, an anti-inflammatory agent, an anesthetic agent, a keratolytic agent, a rubrefacient agent.

23. The adhesive patch of any one of claims 13 to 21, wherein the biomedically-active substance is a medication comprising a member selected from the group consisting of trolamine salicylate, methyl salicylate, menthol, camphor, eucalyptus oil, spearmint oil, hydrocortisone, benzocaine, lidocaine, ibuprofen, salicylic acid and capsicum.

24. A medication-containing adhesive patch for the transdermal delivery of medication into the body of a patient through the skin, the patch comprising:
a flexible pressure-sensitive adhesive matrix including a natural or synthetic polymer and a biomedically-active substance to be absorbed through the skin into the body of the patient;
a porous backing for supporting the matrix, the backing comprising a sheet of water-insoluble material having an upper surface and a lower surface;
the adhesive patch having the following layers proceeding from a lower surface of the adhesive patch to said upper surface of the backing:
(a) an external layer of said adhesive matrix that is located below the lower surface of the backing, the external layer having an exposed surface for bonding to the skin of the patient;
(b) an internal portion of the matrix which partially penetrates the backing so as to be infiltrated within only a lower portion of the porous backing layer;
(c) the backing sheet including a lower filled portion as a layer in which the internal portion of the matrix layer is infiltrated, and an upper layer portion that is free of said matrix;

said biomedically-active substance being dispersed in both portions of the matrix whereby the matrix releases the biomedically-active substance into the skin through said exposed surface thereof; and the backing having an upper surface that is spaced apart from the gel matrix.

25. The medication-containing adhesive patch of claim 24, wherein the patch is coated on said upper surface with a release coating.

26. The medication-containing adhesive patch of claim 25, wherein the release coating is silicone.

27. The medication-containing adhesive patch of claim 24, 25 or 26, wherein the porous backing sheet is a member selected from the group consisting of nonwoven fabric, woven cloth fabric, and open-cell plastic foam.

28. The medication-containing adhesive patch of any one of claims 24 to 27, wherein the matrix comprises a member selected from the group consisting of gum karaya, gum acacia, locust bean gum, guar gum, modified guar gum, maltodextrin, carboxymethylcellulose, carboxypropylcellulose, polyacrylamide and its cogeners,

29 polyacrylic acid, vinyl acetate resin, acrylic ester copolymer, carbohydrate, vinyl acetate/dioctyl maleate copolymer and acrylic polymer.
29. The medication-containing adhesive patch of any one of claims 24 to 27, wherein said matrix includes a hydrophilic hydrocolloid, a humectant, and a polymeric adhesive.

30. The medication-containing adhesive patch of claim 29, wherein the hydrophilic hydrocolloid comprises a member selected from the group consisting of gum karaya, gum acacia, locust bean gum, guar gum, modified guar gum, maltodextrin, carboxymethylcellulose, carboxypropyl-cellulose, polyacrylamide and its cogeners, and polyacrylic acid.

31. The adhesive patch of claim 29 or 30, wherein the humectant comprises a member selected from the group consisting of propylene glycol and glycerin.

32. The adhesive patch of claim 29, 30 or 31, wherein the polymeric adhesive comprises an acrylic.

33. The adhesive patch of claim 32, wherein said acrylic is an acrylic ester copolymer.

34. The adhesive patch of any one of claims 24 to 33, wherein the biomedically-active substance comprises a member selected from the group consisting of trolamine salicylate, methyl salicylate, menthol, camphor, eucalyptus oil, spearmint oil, hydrocortisone, benzocaine, lidocaine, ibuprofen, salicylic acid, capsicum, anti-pruritic agents, anti-inflammatory agents, keratolytic agents and rubefacient agents.

35. A medication-containing adhesive patch for the transdermal delivery of medication into the body of a patient through the skin, the patch comprising:
a flexible pressure-sensitive adhesive hydrocolloidal gel matrix including a natural or synthetic hydrophilic polymer and a biomedically-active substance to be absorbed through the skin into the body of the patient;
a polyhydric alcohol selected from the group consisting of glycerin and propylene glycol dispersed in the matrix;
a hydrophilic resin emulsion adhesive dispersed in the matrix;
a porous backing for supporting the matrix, the backing comprising a sheet of water-insoluble material having an upper surface and a lower surface;

the adhesive patch having the following layers proceeding from a lower surface of the adhesive patch to said upper surface of the backing:
(a) an external layer of said adhesive matrix that is located below the lower surface of the backing, the external layer having an exposed surface for bonding to the skin of the patient;
(b) an internal portion of the matrix which partially penetrates the backing so as to be infiltrated within only a lower portion of the porous backing layer;
(c) the backing sheet including a lower filled portion as a layer in which the internal portion of the matrix layer is infiltrated, and an upper layer portion that is free of said matrix;
said biomedically-active substance being dispersed in both portions of the matrix whereby the matrix releases the biomedically-active substance into the skin through said exposed surface thereof;
the backing having an upper surface that is spaced apart from the gel matrix; and said biomedically-active substance comprising a member selected from the group consisting of capsicum, eucalyptus oil and spearmint.

36. A medication-containing adhesive patch for the transdermal delivery of medication into the body of a patient through the skin, the patch comprising:
a flexible pressure-sensitive adhesive hydrocolloidal gel matrix including a natural or synthetic hydrophilic polymer and a biomedically-active substance to be absorbed through the skin into the body of the patient, the polymer comprising a natural or synthetic polysaccharide;
a humectant comprising a polyhydric alcohol dispersed in said matrix;
a hydrophilic resin emulsion adhesive dispersed in the matrix;
a porous backing for supporting the matrix, the backing comprising a sheet of water-insoluble material having an upper surface and a lower surface;
the adhesive patch having the following layers proceeding from a lower surface of the adhesive patch to said upper surface of the backing:
(a) an external layer of said adhesive matrix that is located below the lower surface of the backing, the external layer having an exposed surface for bonding to the skin of the patient;
(b) an internal portion of the matrix which partially penetrates the backing so as to be infiltrated within only a lower portion of the porous backing layer;

(c) the backing sheet including a lower filled portion as a layer in which the internal portion of the matrix layer is infiltrated, and an upper layer portion that is free of said matrix;
said biomedically-active substance being dispersed in both portions of the matrix whereby the matrix releases the biomedically-active substance into the skin through said exposed surface thereof;
the backing having an upper surface that is spaced apart from the gel matrix; and said biomedically-active substance comprising a member selected from the group of methyl salicylate, spearmint oil, camphor, eucalyptus oil, menthol, trolamine salicylate and capsicum.

37. A non-occlusive medication-containing analgesic adhesive patch for the transdermal delivery of medication into the body of a patient through the skin, for the relief of pain including arthritis, backache, and muscular aches and strains, the patch comprising:
a flexible pressure-sensitive adhesive hydrocolloidal gel matrix as a layer including (1) a natural or synthetic polymer;

(2) a biomedically-active pain-relieving substance dispersed in the gel matrix layer for being absorbed through the skin into the body of the patient;
a flexible backing sheet for supporting the matrix, the backing sheet comprising a sheet of water-insoluble material having an upper surface and a lower surface;
the patch including both the backing sheet and the matrix layer being non-occlusive, with a moisture vapor transmission rate that is greater than that of a person's skin;
the adhesive matrix layer being cured so as to solidify in contact with the backing sheet;
the adhesive patch having the following portions proceeding from a lower surface of the adhesive patch to said upper surface of the backing sheet:
(a) a portion of said pressure-sensitive adhesive matrix layer located below the lower surface of the backing sheet, the layer having an exposed pressure-sensitive adhesive surface for bonding the patch to the skin of the patient;
(b) an upper portion of the matrix bonded to the backing sheet; and (c) the backing sheet having a portion that is free of said matrix, and having an upper surface that is spaced apart from the matrix; and said biomedically-active substance being dispersed in the matrix such that the matrix releases the biomedically-active substance into the body of the patient through said adhesive surface of the matrix that is bonded to the patient's skin.

38. The medication-containing adhesive patch of claim 37, wherein the polymer comprises a member selected from the group consisting of gum karaya, gum acacia, locust bean gum, guar gum, modified guar gum, maltodextrin, carboxy-methylcellulose, carboxypropylcellulose, polyacrylamide, polyacrylic acid, vinyl acetate resin, acrylic ester copolymer, carbohydrate, vinyl acetate/dioctyl maleate copolymer and acrylic polymer.

39. The adhesive patch of claim 37 or 38, wherein the biomedically-active substance comprises a member selected from the group consisting of trolamine salicylate, methyl salicylate, menthol, camphor, eucalyptus oil, spearmint oil, hydrocortisone, benzocaine, lidocaine, ibuprofen, salicylic acid and capsicum.

40. The adhesive patch of claim 37, 38 or 39, wherein the matrix includes a liquid humectant, and the natural or synthetic polymer comprises a water-soluble or water-dispersible hydrocolloid.

41. A non-occlusive medication-containing analgesic adhesive patch for the transdermal delivery of medication into the body of a patient through the skin, for the relief of pain including arthritis, backache, and muscular aches and pains, the patch comprising:
a flexible pressure-sensitive adhesive matrix having a tacky pressure-sensitive surface for bonding the adhesive patch to the skin of the patient, the matrix including (1) a natural or synthetic water-soluble or water-dispersible polymer;
(2) a biomedically-active pain-relieving substance dispersed in the adhesive matrix for being absorbed through the skin into the body of the patient, and comprising a member selected from the group consisting of trolamine salicylate, methyl salicylate, menthol, camphor, eucalyptus oil, spearmint oil, hydrocortisone, benzocaine, lidocaine, ibuprofen, salicylic acid and capsicum;
a flexible backing sheet for supporting the matrix, the backing sheet comprising a sheet of water-insoluble material having an upper surface and a lower surface;

the patch including both the backing sheet and the matrix layer being non-occlusive with a moisture vapor transmission rate of at least about 612 g/m2/24 hr;
the adhesive matrix layer being cured so as to solidify in contact with the backing sheet;
the adhesive patch having the following portions proceeding from a lower surface of the adhesive patch to said upper surface of the backing sheet:
(a) a layer of said matrix located below the lower surface of the backing sheet, the layer having an exposed adhesive surface for bonding the patch to the skin of the patient;
(b) an upper portion of the matrix bonded to the backing sheet; and (c) the backing sheet having a portion that is free of said matrix and having an upper surface that is spaced apart from the matrix; and said biomedically-active substance being dispersed in the matrix such that the matrix releases the biomedically-active substance into the body of the patient through said adhesive surface of the matrix that is bonded to the patient's skin.

42. The adhesive patch of claim 41, wherein the flexible pressure-sensitive adhesive matrix comprises a member selected from the group consisting of gum karaya, gum acacia, locust bean gum, guar gum, modified guar gum, maltodextrin, carboxymethylcellulose, carboxypropyl-cellulose, polyacrylamide, polyacrylic acid, vinyl acetate resin, acrylic ester copolymer, carbohydrate, vinyl acetate/dioctyl maleate copolymer and acrylic polymer.

43. The adhesive patch of claim 41 or 42, wherein the pressure-sensitive adhesive matrix comprises a resin emulsion adhesive.

44. The adhesive patch of claim 43, wherein the resin emulsion adhesive comprises a member selected from the group consisting of a vinyl acetate resin, acrylic ester copolymer, vinyl acetate/dioctyl maleate copolymer and acrylic polymer.

45. The adhesive patch of any one of claims 41 to 44, wherein the natural or synthetic polymer comprises a water-soluble or water-dispersible hydrocolloid, and the matrix includes a liquid humectant.

46. The adhesive patch of claim 45, wherein the humectant comprises a polyhydric alcohol.

47. The adhesive patch of any one of claims 41 to 46, wherein the flexible backing sheet has a release coating applied to a back surface thereof.

48. A non-occlusive medication-containing analgesic adhesive patch for the transdermal delivery of medication into the body of a patient through the skin, for the relief of pain including arthritis, backache, and muscular aches and pains, the patch comprising:
a flexible pressure-sensitive adhesive hydrocolloidal gel matrix including (1) a natural or synthetic polymer comprising a natural or synthetic hydrocolloidal polysaccharide;
(2) a biomedically-active pain-relieving substance dispersed in the matrix for being absorbed through the skin into the body of the patient, the biomedically-active substance comprising a member selected from the group consisting of trolamine salicylate, methyl salicylate, menthol, camphor, eucalyptus oil, spearmint oil, hydrocortisone, benzocaine, lidocaine, ibuprofen, salicylic acid and capsicum;
(3) a humectant comprising a polyhydric alcohol dispersed in said matrix;

(4) a hydrophilic resin emulsion adhesive dispersed in the matrix for enhancing the adhesive qualities of the matrix;
a flexible backing sheet for supporting the matrix, the backing sheet comprising a sheet of water-insoluble material having an upper surface and a lower surface;
the patch including both the backing sheet and the matrix layer being non-occlusive with a moisture vapor transmission rate of at least about 612 g/m2/24 hr;
the adhesive matrix layer being cured so as to solidify in contact with the backing sheet;
the adhesive patch having the following portions proceeding from a lower surface of the adhesive patch to said upper surface of the backing sheet (a) a layer of said matrix located below the lower surface of the backing sheet, the layer having an exposed adhesive surface for bonding the patch to the skin of the patient;
(b) an upper portion of the matrix bonded to the backing sheet;
(c) the backing sheet having a portion that is free of said matrix, and having an upper surface that is spaced apart from the matrix; and said biomedically-active pain-relieving substance being dispersed in the matrix such that the matrix releases the biomedically-active substance into the body of the patient through said adhesive surface of the matrix that is bonded to the patient's skin.

49. The adhesive patch of claim 48, wherein the flexible pressure-sensitive adhesive matrix comprises a member selected from the group consisting of gum karaya, gum acacia, locust bean gum, guar gum, modified guar gum, maltodextrin, carboxymethylcellulose, carboxypropyl-cellulose, polyacrylamide, polyacrylic acid, vinyl acetate resin, acrylic ester copolymer, carbohydrate, vinyl acetate/dioctyl maleate copolymer and acrylic polymer.

50. The adhesive patch of claim 48 or 49, wherein the humectant comprises a polyhydric alcohol selected from the group consisting of glycerol, propylene glycol, ethylene glycol and sorbitol.