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CA1329363C - Apparatus for delivering nitroglycerin to the skin, process for the production thereof and the use thereof - Google Patents

Apparatus for delivering nitroglycerin to the skin, process for the production thereof and the use thereof

Info

Publication number
CA1329363C
CA1329363C CA 575202 CA575202A CA1329363C CA 1329363 C CA1329363 C CA 1329363C CA 575202 CA575202 CA 575202 CA 575202 A CA575202 A CA 575202A CA 1329363 C CA1329363 C CA 1329363C
Authority
CA
Grant status
Grant
Patent type
Prior art keywords
nitroglycerin
adhesive
pressure
sensitive
weight
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CA 575202
Other languages
French (fr)
Inventor
Halvor Jaeger
Hans-Rainer Hoffmann
Reinhold Meconi
Robert-Peter Klein
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
LTS Lohmann Therapie-Systeme GmbH and Co KG
Original Assignee
LTS Lohmann Therapie-Systeme GmbH and Co KG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Grant date
Family has litigation

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by the preceding groups
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/52Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
    • G01N33/521Single-layer analytical elements

Abstract

ABSTRACT OF THE DISCLOSURE
An apparatus for the controlled delivery or release of nitroglycerin to human or animal skin is disclosed. The apparatus is preferably in plaster form with a nitroglycerin-impermeable backing layer, a single or multiple-part reservoir containing a pressure sensitive adhesive single or multiple-part reservoir comprising nitroglycerin in uniform or irregular distribution and, optionally, a removable protective layer impermeable to nitroglycerin. The reservoir is produced using hot melt pressure sensitive adhesives with a processing temperature of about 40 to 80°C, preferably about 40 to 60°C and in the particularly preferred manner about 40 to 55°C. The preferred use of the apparatus is for therapeutic purposes in human and veterinary medicine. A process for the production of the inventive apparatus is also disclosed.

Description

The invention relates to an apparatus for the controlled delivery or release of nitroglycerin to human or animal skin, processes for the production thereof, and to uses thereof. The inventive apparatus is preferably in plaster form with a backing layer impermeable to the nitroglycerin, a pressure sensitive adhesive single or multiple-part reservoir containing nitroglycerin in uniform or irregular distribution and, optionally, a removable protective layer impermeable to the nitroglycerin.
Nitroglycerin plasters are already known. The production of nitroglycerin plasters is problematic in that nitroglycerin is explosive and consequently its evaporation should be avoided.
Hitherto, it has been preferable to work at temperatures which are as low as possible, preferably at ambient temperature. Frequently, the nitroglycerin-containing pressure sensitive adhesive layer has been produced from nitroglycerin solution. The plaster-like, transdermal, therapeutic systems for the delivery or release of nitroglycerin produced were able to fulfil therapeutic requirements, but were complicated and costly to produce. DE-OS 32 22 800 (ALZA) describes a nitroglycerin plaster in which the nitroglycerin-containing matrix is composed of a nonadhesive, viscous mass obtainable at ambient temperature by thickening a nitroglycerin solution with a rheological agent. US Patent No. 3,742,951 (CIBA-GEIGY), German Patent No. 33 15 272 and DE-OS 33 15 245 (LOHMANN/SCHWARZ) all describe simply constructed nitroglycerin plasters with pressure sensitive adhesive matrix materials produced from nitroglycerin solution at ambient temperature. Finally, DE-OS 36 42 931 (CIBA-GEIGY) describes use of multipart nitroglycerin reservoirs.
However, the use of solvents in the production of the pressure sensitive adhesive layer is disadvantageous for several reasons. The preparation of the solutions requires at least one additional rather complicated process stage. It also involves a high technical expenditure and additional costs for handling. For medical purposes extremely pure and thus expensive solvents are re~uired for dissolving the adhesive or its starting materials to ensure a corresponding freedom from residue in the transdermal system. Another problem is in order to ensure freedom solvents in the plaster the use of expensive drying sections and suction plants are needed. Additional costs result from the recovery and separation of the solvent which are needed to avoid prejudicing the environment. A
further risk is in solvent flammability, particularly in the explosive nature of nitroglycerin as in the present case. Most organic solvents are also harmful to the human organism so that rather involved protective measures must be taken to protect the working personnel.
An object of the present invention, therefore, is to avoid the aforementioned disadvantages of the prior art apparatuses and processes.
Accordingly, the invention provides a process for the production of an apparatus for controlled transdermal release of nitroglycerin to skin, with a pressure sensitive adhesive nitroglycerin-reservoir with a distribution of the nitroglycerin, said process comprising producing the pressure sensitive adhesive-nitroglycerin reservoir by introducing the nitroglycerin into the hot melt pressure sensitive adhesive while in a molten state at a processing temperature of 40 to 80C.
The invention also provides an apparatus for the controlled release of nitroglycerin with a pressure sensitive adhesive nitroglycerin reservoir with a distribution of nitroglycerin, wherein the apparatus is produced according to a process in which the pressure sensltive adhesive-nitroglycerin reservoir is produced by introducing the nitroglycerin into the hot melt pressure ,, ,. ~

, ;

1 32936~

sensitive adhesive while in a molten state at a processing temperature of 40 to 80OC.
The invention further provides an apparatus for the controlled release of nitroglycerin to skin, having the form of a plaster, with a backing layer impermeable for nitroglycerin, and a pressure sensitive adhesive reservoir having at least one part comprising a distribution of nitroglycerin, wherein the apparatus is produced according to a process which includes producing the pressure sensitive adhesive-nitroglycerin reservoir by introducing the nitroglycerin into the hot melt pressure sensitive adhesive while in a molten state at a processing temperature of 40 to 80OC.
A further embodiment of the process of invention involves the steps of continuous or discontinuous application of melted hot melt pressure sensitive adhesive, containing the nitroglycerin to be delivered at a hot melt pressure sensitive adhesive temperature between about 40 and 80C, preferably between about 40 and 60C and in the particularly preferred manner between 40 and 55C, to a protective layer material and the optional application of a carrier.
In producing a nitroglycerin reservoir at low temperatures it is possible to operate without solvents.
As a result there is a considerable saving on materials, a faster production without the time-consuming drying stages and no harmful affect to the environment, together which inter 31i~ leads to a much less expensive product by using a harmless production process.
The term hot melt pressure sensitive adhesive when used herein is understood to mean any pressure sensitive adhesive which is adequately liquid when hot to permit problem free application thereof at a temperature above approximately 40C.
Hot melt pressure sensitive adhesives that may be used in the invention include, among others, those that are ~, 1 32q363 known to the expert and to those that are described in DE-OS 15 94 268 (SUN OIL CO.), DE-OS 24 13 979 (E.I. DU PONT
DE NEMOURS), DE-OS 24 35 863 (DYNAMIT NOBEL AG), DE-OS 28 00 302 (CIBA GEIGY), EP-A-104 005 (PERSONAL PRODUCTS CO.), JP 6104 2583 and JP 61 281 810, EP-OS 131 460 (EXXON), EP-OS 234 856 (EXXON), EP-OS 185 992 (EASTMAN KODAX), as well as US Patent No.'s 3,699,963 and 4,358,557 (EASTMAN KODAX) and explicit reference is made to these prior art references to avoid unnecessary repetition.
The basic polymers that are used may be composed of, for example, polyamides, polyesters, polycaprolactams, polycaprolactone, ethylene-vinyl acetate copolymers (EVA), ethylene-ethylacrylate copolymers (EEA), polyvinylethers, polyacrylate esters, polyvinylacetals, polyvinylacetates, styrene-butadine block polymers, isoprene block polymers, polyurethanes, ethylcellulose, cellulose acetate-butyrate, synthetic rubbers (e.g. neoprene rubber), polyisobutylene, butyl rubber, acrylonitrile-butadiene copolymers, epoxy resins, melamine resins, phenol-formaldehyde resins and resorcinol-formaldehyde resins and inter alia the following modifying resins: hydrogenated colophony, polymerized colophony, dimerized resin acids, disproportionated colophony, colophony methyl esters, hydrogenated colophony glycerol esters, hydrogenated colophony methyl esters, pentalesters, hydrogenated colophony triethyleneglycolesters, hydroabiethyl alcohol and its derivatives, glycerol esters, ditriolesters and pentaesters of resin acids, polymerized colophony pentalesters, dimerized colophony pentalesters, dimerized colophony glycerol esters, esters of maleic acid or phenol-modified colophony, aromatic and aliphatic hydrocarbon resins, hydrogenated resins, polyterpene resins, modified terpene resins, waxes, low molecule weight polyethylene and polypropylene and alkyl-styrene copolymers. Optionally, to the8e resins may be added plasticizers, such as e.g.
adipic acid esters, phosphoric acid esters, phthalic acid esters, polyesters, fatty acid esters, citric acid esters or epoxide plasticizers. It is also possible to admix stabilizers, such as tocopherol, substituted phenols, hydroquinones, pyrocatechols, aromatic amines and, optionally, also fillers, such as e.g. titanium dioxide, magnesium oxide, zinc oxide and silicon dioxide.
The formation of the components of the apparatus containing hot melt pressure sensitive adhesives with a processing temperature between about 40 and 80C may be effected by extrusion, pouring, roller application, knife coating, spraying or by a printing process.
A limit value for the processability of the hot melt pressure sensitive adhesive in many of these processes occurs at a viscosity of approximately 80,000 Pa.
If the substrate to be treated with the adhesive, a component of the apparatus, could potentially be damaged by the temperature of the hot-applied adhesive through decomposition, reaction or partial melting, a cooled substrate may be used instead. Cooling may be effected by known processes ~er se such as by the introduction of cold inert gases or by contact with a cooling surface.
The hot melt pressure sensitive adhesive can, e.g., be applied in accordance with a predetermined pattern in layer form or in individual areas to the protective layer or the covering material.
Typical compositions for hot melt pressure sensitive adhesives that may be used include those prepared from between about 10 and 100% by weight, preferably about 20 to 80% by weight and in the particularly preferred manner from about 20 to 50% by weight of polymer; between about 10 and 80% by weight, preferably from about 15 to 60% by weight of plasticizer; between about 10 and 80% by weight, preferably from about 15 to 60% by weight of tackifier; and, optionally, from about 0.1 to 5% by weight of anti-agers and/or from about 0 to 70% by weight of .~

1 3~9363 fillers; the sum of the percentages of the components always being 100.
Preferably, the hot melt pressure sensitive adhesive contains from about 10 to 50% by weight of styrene-isoprene-styrene synthetic rubber, such as is commercially available under the name CARIFLEX TR 1107 of SHELL; between about 10 and 80% by weight of hydrogenated alcohol, such as is commercially available under the name ABITOL from HERCULES; between about 10 and 80~ by weight of a hydrocarbon resin, e.g. HERCURES C from HERCULES;
between about 1 and 40% by weight of esters of vegetable fatty acids, e.g. MIGLYOL 812 of DYNAMIT NOBEL; and, optionally, up to about 5% by weight of anti-agers, such as hydroquinone or the like, as well as up to about 70% by weight of fillers.
For another preferred embodiment of the invention the hot melt pressure sensitive adhesive contains about 10 to 50% by weight of a polycaprolactone, e.g. CAPA 650 of INTEROX; between about 10 and 80% by weight of a hydrogenated alcohol, e.g. ABITOL of HERCULES; between about 10 and 80% by weight of a hydrocarbon resin, e.g.
HERCURES C of HERCULES; between about 1 and 40% by weight of esters of vegetable fatty acids, such as MIGLYOL 812 of DYNAMIT NOBEL; and, optionally, up to about 5% by weight of anti-agers, as well as up to about 70% by weight of filler~.
It can be advantageous for the hot melt pressure sensitive adhesive to have about 10 to 50% by weight of polyethylene-vinyl acetate, such as EVATANE 28-25 of ATOCHEM; between about 10 and 80% by weight of a hydrogenated alcohol, e.g. ABITOL of HERCULES; between about 10 and 80% by weight of a hydrocarbon resin, e.g.
HERCURES C of HERCULES; between about 1 and 40% by weight *trade mark "

of esters of vegetable fatty acids, e.g. MIGLYOL 812 of DYNAMIT NOBEL; and, optionally, up to about 5% by weight of anti-agers, such as hydroquinone or the li~e, and up to about 70% by weight of fillers.
A suitable hot melt pressure sensitive adhesive can contain about 10 to 50% by weight of polyurethane, such as e.g. LUPREN P 1110 of BASF; between about 10 and 80% by weight of a hydrogenated alcohol, e.g. ABITOL of HERCULES;
between about 10 and 80% by weight of a hydrocarbon resin, e.g. HERCURES C of HERCULES; between about 1 and 40% by weight of esters of vegetable fatty acids, e.g. MIGLYOL
812 of DYNAMIT NOBEL; and, optionally, up to about 5% by weight of anti-agers, as well as up to about 70% by weight of fillers.
It is also possible for the hot melt contact adhesive to contain about 10 to 50% by weight of polyamide, such as e.g. EURELON 930 of SCHERING; between about 10 and 80% by weight of a hydrogenated alcohol, e.g. ABITOL of HERCULES; between about 10 and 80% by weight of a hydrocarbon resin, e.g. HERCURES C of HERCULES; between about 1 and 40% by weight of esters of vegetable fatty acids, e.g. MIGLYOL 812 of DYNAMIT NOBEL; and, optionally, up to about 5% by weight of anti-agers, as well as up to about 70% by weight of fillers.
It is also possible to use a hot melt pressure sensitive adhesive with about 10 to 50% by weight of epoxide, e.g. EUREPOX 7001 of SCHERING; between about 10 and 80% by weight of a hydrogenated alcohol, e.g. ABITOL
of HERCULES; between about 10 and 80% by weight of a hydrocarbon resin, e.g. HERCURES C of HERCULES; between about 1 and 40% by weight of esters of vegetable fatty *trade mark acids, e.g. MIGLYOL 812 of DYNAMIT NOBEL; and, optionally, up to about 5% by weight of anti-agers, such as hydroquinone or the like, as well as up to 70~ by weight of fillers.
Another hot melt pressure sensitive adhesive usable in the production of the inventive transdermal systems has about 10 to 50~ by weight of polyisobutene with a tacky, rubber-like consistency, such as e.g. OPPANOL B
of BASF; between about 10 and 80% by weight of hydrogenated alcohol, e.g. ABITOL of HERCULES; between about 10 and 80%
by weight of hydrocarbon resin, e.g. HERCURES C of HERCULES; between about 1 and 40% by weight of esters of vegetable fatty acids, e.g. MIGLYOL 812 of DYNAMIT NOBEL;
and, optionally, up to about 5% by weight of anti-agers, as well as up to about 70% by weight of fillers.
Finally, it is also preferable to use hot melt pressure sensitive adhesives with a polyester base and which e.g. contain between about 10 and 80% by weight of a hydrogenated alcohol, e.g. ABITOL of HERCULES; between about 10 and 80% by weight of a hydrocarbon resin, e.g.
HERCURES C of HERCULES; between about 1 and 40% by weight of esters of vegetable fatty acids, e.g. MIGLYOL 812 of DYNAMIT NOBEL; and, optionally, up to about 5% by weight of anti-agers, as well as up to about 70% by weight of fillers.
The apparatus of invention may have one or more nitroglycerin reservoirs, in which the nitroglycerin is present in a concentration greater than the active substance-possessing hot melt pressure sensitive adhesive layer. This allows higher nitroglycerin doses to be processed and as a result the apparatus may remain in use *trade mark : . .

longer prior to being replaced. Typical constructions appear in DE-OS 36 29 304 (LOHMANN).
The production of the melts necessary for the inventive apparatus is by known processes ~E se. During the processing of nitroglycerin, an explosive and volatile substance, the following processing measures are advantageous:
A) working at temperatures which are as low as possible, lo B) raising the external pressure by known measures, C) saturation of the vapour chamber over the melt with the vaporous nitroglycerin and working in an en~apsulated system, and D) working with the minimum nitroglycerin proportion in the melt.
It is desirable to work within a closed system in order to avoid unregulated evaporation of the nitroglycerin and a possible collection of explosive quantities of the nitroglycerin in cool regions of the plant, such as e.g.
in exhaust systems.
In drawings which illustrate embodiments of the invention, Figure 1 shows schematically a section through a preferred embodiment of the apparatus of the invention with nitroglycerin depot;
Figure 2 shows schematically a section through a further preferred embodiment of the invention with a nitroglycerin depot; and Figure 3 shows schematically a section through another embodiment of the inventive apparatus without an active substance depot.
With re~erence to Figure 1, a preferred embodiment of the inventive apparatus as a transdermal system for the delivery o~ nitroglycerin to the skin is shown. It contains a nitroglycerin-permeable hot melt ,-;

1 32q363 pressure sensitive adhesive 12, a nitroglycerin depot 14 in which the nitroglycerin has a greater concentration than in the hot melt pressure sensitive adhesive 12, and a nitroglycerin-impermeable backing layer lo on which rests the nitroglycerin depot 14. The apparatus is affixed to the skin 18.
Nitroglycerin migrates continuously at a predetermined rate through the hot melt pressure sensitive adhesive and into the skin 18, such that the nitroglycerin content of the hot melt pressure sensitive adhesive 12 decreases. The reduction in the nitroglycerin concentration is compensated for by an after-flow of nitroglycerin from the nitroglycerin depot 14.
Accordingly, over a predetermined period of time there is a predeterminable equilibrium concentration of the nitroglycerin in the hot melt pressure sensitive adhesive 12, which ensures the delivery of constant nitroglycerin quantities to the skin 18.
Referring now to Figure 2, a further preferred embodiment of the invention is shown in which a nitroglycerin depot 14 is surrounded on all sides by hot melt pressure sensitive adhesive 12. This embodiment is particularly appropriate when a large contact surface between the nitroglycerin depot and the hot melt pressure sensitive adhesive i8 desired for the rapid release of nitroglycerin to the adhesive.
With reference to Figure 3, another preferred embodiment of the invention is shown in which a nitroglycerin-containing hot melt pressure sensitive adhesive 12 is applied to a nitroglycerin-impermeable backing material 10 in such a way that the latter covers the adhesive 12 on three sides. By means of the free hot melt pressure sensitive adhesive surface, the same is affixed to the skin 18, so that a whole-area contact is ensured over the entire application surface. This allows the transfer of nitroglycerin from the hot melt pressure ,~
~,i 1 32~363 sensitive adhesive to the skin to always take place over a constant surface and at a constant speed.
The inventively improved production of a nitroglycerin-containing transdermal system will now be described. Firstly, a mixture of the components of the hot melt pressure sensitive adhesive is prepared with the nitroglycerin. This mixture is brought to the processing temperature and applied from the melt to a backing material. The further processing, such as the application of an adhesively finished protective layer material takes place in the conventional way. The nitroglycerin may be incorporated into the hot melt pressure sensitive adhesive either both in a solution, preferably dissolved in one of the components of the adhesive, or adsorbed onto a carrier material, such as lactose.
A distinct advantage of the inventive process is that following the application of the hot melt pressure sensitive adhesive, (e.g. by means of a large slot nozzle), both the carrier or protective layer material may be lined upon so that through covering the hot melt pressure sensitive adhesive layer, evaporation of the nitroglycerin in the freshly prepared system can be suppressed.
The following example in which the production of a nitroglycerin plaster is described further illustrates the invention.
Example 15.5g of an ethylene-vinylacetate copolymer, (such as commercially available under the name EVATANE
28-25 from ATOCHEM) was mixed with 20.4g of hydroabietyl alcohol, ~uch as commercially available under the name ABITOL from HERCULES), 30.4g of a tackifier based on aliphatic hydrocarbon resins, (such as commercially available under the name HERCURES C* from HERCULES), and 3.4g of a plasticizer based on esters of middle-chain *trade mark 1 32q363 vegetable fatty acids (such as commercially available under the name NIGLYOL 812 from DYNANIT NOBEL) and the mixture was then melted at a temperature of 110C. After cooling to about 50 to 60C, to this mixture, accompanied by stirring, was added 26.6g of nitroglycerin-lactose triturate (corresponding to 2.7g of pure nitroglycerin).
The mixture was then coated onto a polyester film siliconized and aluminum vapour treated on one side (weight per unit area of adhesive film 402 g/m2) and an aluminized polyester film was then applied thereto. The thus obtained laminate was cut into 16 cm2 rectangular plasters and individually packed in sealed bags in the known manner.

* trade-mark

Claims (26)

1. A process for the production of an apparatus for controlled transdermal release of nitroglycerin to skin, with a pressure sensitive adhesive nitroglycerin-reservoir with a distribution of the nitroglycerin, said process comprising producing the pressure sensitive adhesive-nitroglycerin reservoir by introducing the nitroglycerin into the hot melt pressure sensitive adhesive while in a molten state at a processing temperature of 40 to 80°C.
2. A process according to claim 1, wherein the apparatus is in the form of a plaster.
3. A process according to claim 1, wherein the processing temperature of the hot melt pressure sensitive adhesive is between 40 and 60°C.
4. A process according to claim 1, wherein the processing temperature of the hot melt pressure sensitive adhesive is between 40 and 55°C.
5. A process according to claim 1, wherein the hot melt pressure sensitive adhesive is applied on a basis of material selected from the group consisting of styrene-isoprene-styrene block polymers, polycaprolactones, ethylene-vinylacetate-copolymers, polyurethanes, polyepoxides, polyisobutenes, and polyvinylethers.
6. A process according to claim 5, wherein the basis further includes material selected from the group consisting of plasticisers, tackifiers, fillers, anti-agers and thixotropic agents.
7. A process according to claim 1, wherein the hot melt pressure sensitive adhesive is produced from between 10 and 80% by weight of polymer, between 1 and 80%
by weight of plasticiser, and between 10 and 80% by weight of tackifier; the sum of percentages of the components being 100.
8. A process according to claim 7, wherein the hot melt pressure sensitive adhesive is produced from between 20 and 80% by weight of polymer.
9. A process according to claim 7, wherein the hot melt pressure sensitive adhesive is produced from between 20 to 50% by weight of polymer.
10. A process according to claim 7, wherein the hot melt pressure-sensitive adhesive is produced from between 15 to 60% by weight of plasticisers.
11. A process according to claim 7, wherein the hot melt pressure sensitive adhesive is produced from between 15 to 60% by weight of tackifier.
12. A process according to claim 7, and further comprising 0.1 to 5% by weight of anti-agers.
13. A process according to claim 7, and further comprising 0 to 70% by weight of fillers.
14. A process according to claim 1, wherein nitroglycerin containing melted hot melt pressure sensitive adhesive is applied at a temperature of the hot melt pressure sensitive adhesive of between 40 to 80°C onto a carrier.
15. A process according to claim 14, wherein the temperature of the hot melt pressure sensitive adhesive is between 40 to 60°C.
16. A process according to claim 14, wherein the temperature of the hot melt pressure sensitive adhesive is between 40 to 55°C.
17. A process according to claim 14, and further applying a protective layer of material to the apparatus.
18. A process for the production of an apparatus according to claim 1, which comprises continuous or discontinuous application of nitroglycerin containing melted hot melt pressure sensitive adhesive at a temperature of the hot melt pressure sensitive adhesive between 40 and 80°C onto a protective layer material.
19. A process according to claim 18, wherein the temperature of the hot melt pressure sensitive adhesive is between 40 to 60°C.
20. A process according to claim 18, wherein the temperature of the hot melt pressure sensitive adhesive is between 40 to 55°C.
21. A process according to claim 18, and further comprising applying the melted hot melt pressure sensitive adhesive containing nitroglycerin onto a carrier.
22. A process for the production of an apparatus according to claim 14, wherein the formation of the components of the apparatus that contain the hot melt pressure sensitive adhesive takes place at a processing temperature of between 40 and 80°C, by extrusion, pouring, roller application, knife coating, spraying or printing process.
23. An apparatus for the controlled release of nitroglycerin with a pressure sensitive adhesive nitroglycerin reservoir with a distribution of nitroglycerin, wherein the apparatus is produced according to a process in which the pressure sensitive adhesive-nitroglycerin reservoir is produced by introducing the nitroglycerin into the hot melt pressure sensitive adhesive while in a molten state at a processing temperature of 40 to 80°C.
24. An apparatus according to claim 23, wherein the hot melt pressure sensitive adhesive having distribution of nitroglycerin comprises at least one layer thereof.
25. An apparatus according to claim 23, and further comprising a detachable protective layer.
26. An apparatus for the controlled release of nitroglycerin to skin, having the form of a plaster, with a backing layer impermeable for nitroglycerin, and a pressure sensitive adhesive reservoir having at least one part comprising a distribution of nitroglycerin, wherein the apparatus is produced according to a process which includes producing the pressure sensitive adhesive-nitroglycerin reservoir by introducing the nitroglycerin into the hot melt pressure sensitive adhesive while in a molten state at a processing temperature of 40 to 80°C.
CA 575202 1987-09-01 1988-08-19 Apparatus for delivering nitroglycerin to the skin, process for the production thereof and the use thereof Expired - Fee Related CA1329363C (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
DE3729165 1987-09-01
DEP3729165.3 1987-09-01
DE19873743946 DE3743946C2 (en) 1987-09-01 1987-12-23
DEP3743946.4 1987-12-23

Publications (1)

Publication Number Publication Date
CA1329363C true CA1329363C (en) 1994-05-10

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
CA 575202 Expired - Fee Related CA1329363C (en) 1987-09-01 1988-08-19 Apparatus for delivering nitroglycerin to the skin, process for the production thereof and the use thereof

Country Status (10)

Country Link
US (1) US5126144A (en)
EP (1) EP0305758B1 (en)
JP (1) JP2795862B2 (en)
KR (1) KR970006446B1 (en)
CA (1) CA1329363C (en)
DE (2) DE3743946C2 (en)
DK (1) DK210489D0 (en)
ES (1) ES2047512T3 (en)
FI (1) FI96578C (en)
WO (1) WO1989001788A1 (en)

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FI892054A (en) 1989-04-28 application
DE3743946A1 (en) 1989-03-09 application
WO1989001788A1 (en) 1989-03-09 application
ES2047512T3 (en) 1994-03-01 grant
JPH02500595A (en) 1990-03-01 application
KR970006446B1 (en) 1997-04-28 grant
DK210489D0 (en) 1989-04-28 grant
EP0305758B1 (en) 1993-12-22 grant
FI96578B (en) 1996-04-15 application
US5126144A (en) 1992-06-30 grant
DE3886478D1 (en) 1994-02-03 grant
EP0305758A1 (en) 1989-03-08 application
FI96578C (en) 1996-07-25 grant
JP2795862B2 (en) 1998-09-10 grant
DK210489A (en) 1989-04-28 application

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