CA1333688C - Device for the delivery of substances, process for the production thereof and use thereof - Google Patents
Device for the delivery of substances, process for the production thereof and use thereofInfo
- Publication number
- CA1333688C CA1333688C CA000575201A CA575201A CA1333688C CA 1333688 C CA1333688 C CA 1333688C CA 000575201 A CA000575201 A CA 000575201A CA 575201 A CA575201 A CA 575201A CA 1333688 C CA1333688 C CA 1333688C
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- Prior art keywords
- hot melt
- sensitive adhesive
- melt pressure
- weight
- substance
- 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 - Lifetime
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/58—Adhesives
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/52—Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
- G01N33/521—Single-layer analytical elements
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Urology & Nephrology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Dermatology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Materials Engineering (AREA)
- Biotechnology (AREA)
- Medicinal Preparation (AREA)
- Adhesives Or Adhesive Processes (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Fats And Perfumes (AREA)
- Containers And Plastic Fillers For Packaging (AREA)
- Extrusion Moulding Of Plastics Or The Like (AREA)
- Refuse Collection And Transfer (AREA)
- Peptides Or Proteins (AREA)
- Coating Apparatus (AREA)
- Lubricants (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
A device for the release or delivery of substances in a uniform or irregular distribution from hot melt pressure-sensitive adhesives is disclosed. The hot melt pressure-sensitive adhesive may have a processing temperature between about 40 and 80°C, preferably between about 40 and 60°C and most preferably between about 40 and 55°C. The inventive device may be applied in human and veterinary medicine, for diagnostic purposes or for use with cosmetics. A process for the production of the device is also disclosed.
Description
The invention relates to a device for the release - of substances in a uniform or irregular distribution from hot melt pressure-sensitive adhesives, a process for the preparation of the device and to the use thereof.
Typical examples of such devices include active substance-containing plasters, indicator systems, perfume-releasing devices and the like, and are particularly used in the medical field for the controlled or uncontrolled release of substances. Particular significance has been attached to controlled devices in the form of transdermally controlled systems. The application of an active substance-containing layer from a melt to such devices is known. For example, EP-OS 0177893 discloses a nonadhesive cellulose ether gel which can be applied from a melt and in which active substances can be distributed. This gel is hot processed and is nonadhesive. As well, DE-OS 32 22 800 describes a transdermal system, in which active substance packed in microcapsules is present in a thermally shapeable, adhesive matrix material, which is applied from the melt. For temperature-sensitive active substances with a low melting point or which can be easily decomposed, attempts have also been made to produce nonadhesive active substance-containing matrices at ambient temperature. For example, it is taught in US Patent No. 4,379,454 (Campbell et. al.) that an active substance solution brought to a desired viscosity value by means of gelling agents at ambient temperature can be used for the active substance layer. It is known from US Patent 13336~8 No. 4,559,222 (Enscore et. al.) to use a mixture of mineral - oil/polyisobutylene and colloidal silicon dioxide prepared at ambient temperature as a viscous active substance layer for oil-soluble active substances, whereby said layers can also be made in pressure-sensitive adhesive manner. DE-OS
32 22 800 (ALZA) describes an active substance layer from an active substance solution thickened by means of a rheological agent, such as cellulose, a polysaccharide or a silicon compound, which is nonadhesive and is also suitable for rapid active substance release.
US Patent No. 3,923,939 discloses the shaping of active substances, such as tetracycline, in an ethylene-vinyl acetate copolymer layer by melt pressing. EP-OS 86 468 describes an oral antidiabetes sulphonyl urea derivative in a nonadhesive hot melt mass and with a melting point of 30 to 90C filled into capsules in predetermined doses from the melt. As well, US Patent No. 3,957,966 teaches that active substances can be processed in nonadhesive hot melt masses.
DE-OS 30 07 363 describes the use of a pressure-sensitive adhesive mixture of a thermoplastic elastomer, preferably a block polymer of general formula A-B-A, a tackifying resin with oil or higher fatty acids and an active substance for producing a simple transdermal system.
The pressure-sensitive adhesive mixture described is only suitable for relatively temperature-resistant active substances, which are able to withstand temperatures of ,, 120C and higher. US Patent No. 3,699,963 teaches mixing - oxytocin with pressure-sensitive adhesive for producing a transdermal therapeutic system and the shaping thereof at a temperature above 90C. The thus produced transdermal systems are inexpensive to produce and ensure a constant active substance transfer via the whole-area adhesion of the system to the skin.
The prior art processes for producing such systems are not suitable for transdermal systems containing temperature-sensitive substances, such as scopolamine.
Therefore, hitherto, pressure-sensitive adhesive active substance layers with temperature sensitive active substances have preferably been formed from the solution and the solvent evaporated.
The use of solvents in the preparation of active substance-containing adhesive layers is disadvantageous for several reasons. The preparation of the solutions requires at least one additional, complicated process stage. It requires significant technical effort and expenditure in terms of the handling of the solvents, and when used for medical purposes it is additionally necessary to use extremely pure and, accordingly, expensive solvents; in order to ensure a corresponding freedom from residue in the apparatus for the dissolving of the adhesive or its starting materials. Another problem is in achieving freedom from solvent in the device, for which purpose it is necessary to use expensive drying sections and suction installations.
~ .
Costs are also incurred through the recovery or separation - of the solvent, in order to avoid pollution of the environment. An additional risk is in the flammability of most solvents. Furthermore, most organic solvents are harmful to the human organism, so that complicated and costly protective measures must be taken for personnel working in the plant.
An object of the present invention, therefore, is to eliminate the aforementioned disadvantages of the devices and processes of the prior art.
Accordingly, the invention provides a device for the release of a substance from a hot melt pressure sensitive adhesive having a non-uniform or uniform distribution of the substances in the hot melt pressure sensitive adhesives, wherein a mixture of hot melt pressure sensitive adhesive and substance or a solution of the substance in the hot melt pressure sensitive adhesive is present, the hot melt pressure sensitive adhesive having a processing temperature between about 40 and 80C, preferably between about 40 and 60C and more preferably between about 40 and 55C.
The invention makes it possible to work without solvents at low temperature such that there is a considerable saving on materials, a speedier production of the device without the time consuming drying stages, as well as a production of the inventive devices which leads to less pollution of the environment, which inter alia leads to a significantly less expensive and solvent-free product.
The process for the production of the device of the invention involves the continuous or discontinuous application of melted hot melt pressure-sensitive adhesive, containing the substance to be released 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 about 40 and 55C, to lo a carrier and, optionally, application of protective layer material.
A further embodiment of the process of the invention involves the continuous or discontinuous application of melted hot melt pressure-sensitive adhesive, containing the substance to be released 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 about 40 and 55C, to a protective layer material and, optionally, application of the carrier.
When using highly volatile and/or thermally unstable substances to be released, the following measures are appropriate for processing purposes:
A) working at very low temperatures, B) increasing the external pressure in order to reduce evaporation, i,"
1~2~ o~
~ ~ o ~
C) saturation of the vapour chamber over the melt - with the vaporous substance, and D) working with a minimum quantity of volatile substance in the melt.
Clearly these measures, such as, e.g. working in an encapsulated plant, are limited by the rules known to the expert according to the intended use of the device to be produced and material circumstances.
The inventive devices, particularly transdermal systems can, for example, be used for local or systemic transdermal active substance administration in human or veterinary medicine or for cosmetic use and are, preferably, used for the release of temperature-sensitive and/or highly volatile substances.
Hot melt pressure-sensitive adhesive is herein understood to mean any pressure-sensitive adhesive which is adequately liquid when hot to permit problem free application at a temperature above approximately 40C.
As inventively operable hot melt pressure-sensitive adhesives may be used inter alia those which are known to the expert as well as those described inter alia 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 KODAK), as well as US Patents Nos. 3,699,963 and 4,358,557 (EASTMAN KODAK) and 1333~88 explicit reference is made to this prior art to avoid unnecessary repetition.
The basic polymers may be composed of, for example, polyamides, polyesters, polycaprolactams, poly-caprolactone, 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 can be used: hydrogenated colophony, polymerized colophony, dimerized resin acids, dis-proportionated 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 penta-esters 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 molecular weight polyethylene and poly-propylene and alkyl-styrene copolymers. To these resins can , . ~
8~
optionally be added platicizers, 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 components of the device, containing hot melt pressure-sensitive adhesive with a processing temperature between about 40 and 80~C, can take place by extrusion, pouring, roller application, knife coating, spraying or by printing processes.
A limiting value for the processability of the hot melt pressure-sensitive adhesive in many of these processes is a viscosity of approximately 80,000 Pa.
If the substrate to be treated with the adhesive, a component of the device, could be damaged by the temperature of the hot-applied adhesive, either by decomposition, reaction or partial melting, it is possible to use a cooled substrate. Cooling can take place by E~_ se known processes, such as by the introduction of cold inert gases or by contact with a cooling surface.
The hot melt pressure-sensitive adhesive can, for example, be applied in layer form or in individual areas, in accordance with a predetermined pattern, to the protective layer or the covering material. In a preferred embodiment, 133~688 the hot melt pressure-sensitive adhesive containing the substance or substances to be delivered is present in the form of one or more layers.
Depending upon the function of the intended use (and, e.g., if the substance to be released is to be released through the backing layer, such as can be the case with essential oils, such as fragrances), the hot melt pressure-sensitive adhesive may be finished with a carrier permeable with respect to the substance or substances to be released. However, in the embodiment of the device as a transdermal system, where the substance is only to be delivered to the skin, preference is given to a backing layer which is impermeable for the substance to be delivered.
In another preferred embodiment the device further comprises a removable protective layer.
The inventive process makes it possible to obviate the use of solvent-containing pressure-sensitive adhesive materials in the processing of temperature-sensitive, highly volatile substances. This significantly increases the safety of production since it is now certain that no toxic solvent residues can remain in the medicinal administration form. As well, the application process is greatly simplified and considerable cost savings in terms of production is achieved. Naturally, the process can also be used in an advantageous manner for less temperature-1~33688 sensitive substances as this also leads to considerable costsavings.
The term "substances" in connection with the present invention is understood to mean chemical elements, organic or inorganic compounds, which can migrate out of the components containing them in such a device and can thereby bring about a sought after effect. Among the uses of the inventive device particular significance is attached to human and veterinary medicine, a realization of the invention in plaster form being particularly preferred.
Typical substances which can be administered by means of the devices of invention include: aceclidine, amphetaminil, amphetamine, amylnitrite, apophedrin, atebrin, alprostadil, azulene, arecoline, anethole, amylenehydrate, acetylcholine, acridine, adenosintriphosphoric acid, L-malic acid, alimemazine, allithiamine, allyl isothiocyanate, amino-ethanol, apyzine, apiol, azatadine, alprenolol, ethinazone, benzoylperoxide, benzyl alcohol, bisabolol, bisnorephedrine, butacetoluid, benactyzine, campher, colecalciferol, choralhydrate, clemastine, chlorobutanol, capsaicin, cyclopentamine, clobutinol, chamazulene, cimethocaine, codeine, chloropromazine, quinine, chlorothymol, cyclophosphamide, cinchocaine, chlorambucil, chlorphenesin, diethylethane, divinylethane, dexchlorpheniramine, dinoprostone, dixyrazine, ephedrine, ethosuximide, enallylpropymal, emylcamate, erytroltetra-nitrate, emetine, enflurane, eucalyptol, etofenamate, ~J ' I33368~
ethylmorphine, fentanyl, fluanisone, guajazulene, holathane, hyoscyamine, histamine, fencarbamide, hydroxycaine, hexylresorcinol, isoaminlcitrate, isosorbidedinitrate, ibuprofin, iodine, iodoform, isoaminile, lidocaine, lopirine, levamisole, methadone, methyprylone, methyl-phenidate, mephenesine, methylephedrine, meclastine, methopromazine, mesuximide, nicethamide, norpseudoephedrine, menthosl, methoxyflurane, methylpentinol, metixen, misoprostol, oxytetracaine, oxyprenolol, oxyphenbutazone, oxyquinoline, pinene, prolintane, procylidine, piperazine, pivazide, phensuzimide, procaine, phenindamine, promethazine, pentetrazole, profenamine, perazine, phenol, pethidine, pilocarpine, prenylamine, phenoxybenzamine, resochin, scopolamine, salicylic acid ester, sparteine, trichloroethylene, timolol, trifluperazine, tetracaine, trimipramine, tranylcypromine, trimethadione, tybamate, thymol, thioridazine, valproic acid, verapamil, as well as other active substances which can be taken up through the skin. Obviously, this list is not exhaustive.
Typical compositions for the hot melt pressure-sensitive adhesives to be used are those prepared from between about 10 and 100% by weight, preferably about 20 to 80% by weight and in the particularly preferred manner about 20 to 50% by weight of polymer; between about 10 and 80% by weight, preferably about 15 to 60% by weight of plasticizer;
between about 10 and 80% by weight, preferably about 15 to 60% by weight of tackifier; and, optionally, about 0.1 to 5%
by weight of anti-agers and/or about 0 to 70% by weight of fillers; the sum of the percentages of the components always being 100.
Preferably, the hot melt pressure-sensitive adhesive contains 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 a hydrogenated alcohol, such as is commercially available under the name ABITOL~ from HERCULES; between about 10 and 80% by weight of a hydro-carbon 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, etc., as well as up to about 70% by weight of fillers.
In a further preferred embodiment of the invention the hot melt pressure-sensitive adhesive has 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 fillers.
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 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, etc., 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. LUPHEN 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 pressure-sensitive 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, -` 1333688 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 hydrogenated alcohol, e.g. ABITOL~ of HERCULES; between about 10 and 80% by weight of a hydro-carbon 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, such as hydroquinone, etc., as well as up to about 70% by weight of fillers.
Another hot melt pressure-sensitive adhesive operable in the production of the inventive transdermal systems has about 10 to 50% by weight of polyisobutine with a tacky, rubber-like consistency, such as e.g. OPPANOL B 50~
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.
Finally, it is preferred 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~ 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 devices of the invention may also contain one or more substance depots in which the substance is present in a higher concentration than the active substance-containing hot melt pressure-sensitive adhesive layer, so that higher substance doses can be processed and consequently the device can remain in use longer before it has to be changed. Typical constructions appear e.g. in DE-OS 36 29 304.
In drawings which illustrate embodiments of the invention, Figure 1 is a sectional view through the layers of a preferred device of invention with a substance depot;
Figure 2 is a sectional view through the layers of a further preferred device of the invention with an active substance depot: and Figure 3 is a sectional view through the layers of another embodiment of the inventive device without a substance depot.
With reference to Figure 1, a preferred embodiment of the device of the invention is shown which is in the form of a plaster-like, active substance-containing, transdermal, therapeutic system. It comprises a hot melt pressure-sensitive adhesive layer 12, an active substance depot 14 in which the active substance has a higher concentration than in the hot melt pressure-sensitive adhesive layer 12, as well as an active substance-impermeable carrier 10, on which rests the active substance depot 14 and which is affixed to the skin 18. Active substance continuously migrates at a predetermined rate through the skin 18 such that the active substance content of layer 12 decreases. The active substance decrease is compensated by an after-flow of active substance from the active substance depot 14, so that over a predetermined period of time there is an equilibrium concentration of the active substance in the hot melt pressure-sensitive adhesive layer 12, which ensures the delivery of a constance active substance quantity of the skin 18.
Referring now to Figure 2, another embodiment of the inventive device is shown, in which an active substance depot 14 is surrounded on all sides by the hot melt pressure-sensitive adhesive layer 12. This embodiment is particularly suitable if a large pressure-sensitive surface between the active substance depot and the hot melt pressure-sensitive adhesive layer is desired for a rapid active substance delivery to the hot melt pressure-sensitive adhesive layer.
With reference to Figure 3, a further embodiment of the inventive device is shown, in which an active substance-containing hot melt pressure-sensitive adhesive layer 12 is applied to an impermeable carrier material 10 in such a way that the latter covers the layer 12 on three sides. With the free hot melt pressure-sensitive adhesive surface it is affixed to the skin 18, so that a whole-area contact is ensured over the application time and the transfer of the active substance to the skin always takes place over a constant surface and at a constant speed.
The inventively improved production of the device of the invention will now be described. Firstly, the mixture of the components of the hot melt pressure-sensitive adhesive and the substance to be administered is prepared.
This mixture is then brought to the processing temperature and applied from the melt to a carrier material. The necessary further processing, such as the application of an adhesively finished protective layer material, may take place in the conventional manner.
Typical examples of such devices include active substance-containing plasters, indicator systems, perfume-releasing devices and the like, and are particularly used in the medical field for the controlled or uncontrolled release of substances. Particular significance has been attached to controlled devices in the form of transdermally controlled systems. The application of an active substance-containing layer from a melt to such devices is known. For example, EP-OS 0177893 discloses a nonadhesive cellulose ether gel which can be applied from a melt and in which active substances can be distributed. This gel is hot processed and is nonadhesive. As well, DE-OS 32 22 800 describes a transdermal system, in which active substance packed in microcapsules is present in a thermally shapeable, adhesive matrix material, which is applied from the melt. For temperature-sensitive active substances with a low melting point or which can be easily decomposed, attempts have also been made to produce nonadhesive active substance-containing matrices at ambient temperature. For example, it is taught in US Patent No. 4,379,454 (Campbell et. al.) that an active substance solution brought to a desired viscosity value by means of gelling agents at ambient temperature can be used for the active substance layer. It is known from US Patent 13336~8 No. 4,559,222 (Enscore et. al.) to use a mixture of mineral - oil/polyisobutylene and colloidal silicon dioxide prepared at ambient temperature as a viscous active substance layer for oil-soluble active substances, whereby said layers can also be made in pressure-sensitive adhesive manner. DE-OS
32 22 800 (ALZA) describes an active substance layer from an active substance solution thickened by means of a rheological agent, such as cellulose, a polysaccharide or a silicon compound, which is nonadhesive and is also suitable for rapid active substance release.
US Patent No. 3,923,939 discloses the shaping of active substances, such as tetracycline, in an ethylene-vinyl acetate copolymer layer by melt pressing. EP-OS 86 468 describes an oral antidiabetes sulphonyl urea derivative in a nonadhesive hot melt mass and with a melting point of 30 to 90C filled into capsules in predetermined doses from the melt. As well, US Patent No. 3,957,966 teaches that active substances can be processed in nonadhesive hot melt masses.
DE-OS 30 07 363 describes the use of a pressure-sensitive adhesive mixture of a thermoplastic elastomer, preferably a block polymer of general formula A-B-A, a tackifying resin with oil or higher fatty acids and an active substance for producing a simple transdermal system.
The pressure-sensitive adhesive mixture described is only suitable for relatively temperature-resistant active substances, which are able to withstand temperatures of ,, 120C and higher. US Patent No. 3,699,963 teaches mixing - oxytocin with pressure-sensitive adhesive for producing a transdermal therapeutic system and the shaping thereof at a temperature above 90C. The thus produced transdermal systems are inexpensive to produce and ensure a constant active substance transfer via the whole-area adhesion of the system to the skin.
The prior art processes for producing such systems are not suitable for transdermal systems containing temperature-sensitive substances, such as scopolamine.
Therefore, hitherto, pressure-sensitive adhesive active substance layers with temperature sensitive active substances have preferably been formed from the solution and the solvent evaporated.
The use of solvents in the preparation of active substance-containing adhesive layers is disadvantageous for several reasons. The preparation of the solutions requires at least one additional, complicated process stage. It requires significant technical effort and expenditure in terms of the handling of the solvents, and when used for medical purposes it is additionally necessary to use extremely pure and, accordingly, expensive solvents; in order to ensure a corresponding freedom from residue in the apparatus for the dissolving of the adhesive or its starting materials. Another problem is in achieving freedom from solvent in the device, for which purpose it is necessary to use expensive drying sections and suction installations.
~ .
Costs are also incurred through the recovery or separation - of the solvent, in order to avoid pollution of the environment. An additional risk is in the flammability of most solvents. Furthermore, most organic solvents are harmful to the human organism, so that complicated and costly protective measures must be taken for personnel working in the plant.
An object of the present invention, therefore, is to eliminate the aforementioned disadvantages of the devices and processes of the prior art.
Accordingly, the invention provides a device for the release of a substance from a hot melt pressure sensitive adhesive having a non-uniform or uniform distribution of the substances in the hot melt pressure sensitive adhesives, wherein a mixture of hot melt pressure sensitive adhesive and substance or a solution of the substance in the hot melt pressure sensitive adhesive is present, the hot melt pressure sensitive adhesive having a processing temperature between about 40 and 80C, preferably between about 40 and 60C and more preferably between about 40 and 55C.
The invention makes it possible to work without solvents at low temperature such that there is a considerable saving on materials, a speedier production of the device without the time consuming drying stages, as well as a production of the inventive devices which leads to less pollution of the environment, which inter alia leads to a significantly less expensive and solvent-free product.
The process for the production of the device of the invention involves the continuous or discontinuous application of melted hot melt pressure-sensitive adhesive, containing the substance to be released 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 about 40 and 55C, to lo a carrier and, optionally, application of protective layer material.
A further embodiment of the process of the invention involves the continuous or discontinuous application of melted hot melt pressure-sensitive adhesive, containing the substance to be released 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 about 40 and 55C, to a protective layer material and, optionally, application of the carrier.
When using highly volatile and/or thermally unstable substances to be released, the following measures are appropriate for processing purposes:
A) working at very low temperatures, B) increasing the external pressure in order to reduce evaporation, i,"
1~2~ o~
~ ~ o ~
C) saturation of the vapour chamber over the melt - with the vaporous substance, and D) working with a minimum quantity of volatile substance in the melt.
Clearly these measures, such as, e.g. working in an encapsulated plant, are limited by the rules known to the expert according to the intended use of the device to be produced and material circumstances.
The inventive devices, particularly transdermal systems can, for example, be used for local or systemic transdermal active substance administration in human or veterinary medicine or for cosmetic use and are, preferably, used for the release of temperature-sensitive and/or highly volatile substances.
Hot melt pressure-sensitive adhesive is herein understood to mean any pressure-sensitive adhesive which is adequately liquid when hot to permit problem free application at a temperature above approximately 40C.
As inventively operable hot melt pressure-sensitive adhesives may be used inter alia those which are known to the expert as well as those described inter alia 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 KODAK), as well as US Patents Nos. 3,699,963 and 4,358,557 (EASTMAN KODAK) and 1333~88 explicit reference is made to this prior art to avoid unnecessary repetition.
The basic polymers may be composed of, for example, polyamides, polyesters, polycaprolactams, poly-caprolactone, 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 can be used: hydrogenated colophony, polymerized colophony, dimerized resin acids, dis-proportionated 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 penta-esters 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 molecular weight polyethylene and poly-propylene and alkyl-styrene copolymers. To these resins can , . ~
8~
optionally be added platicizers, 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 components of the device, containing hot melt pressure-sensitive adhesive with a processing temperature between about 40 and 80~C, can take place by extrusion, pouring, roller application, knife coating, spraying or by printing processes.
A limiting value for the processability of the hot melt pressure-sensitive adhesive in many of these processes is a viscosity of approximately 80,000 Pa.
If the substrate to be treated with the adhesive, a component of the device, could be damaged by the temperature of the hot-applied adhesive, either by decomposition, reaction or partial melting, it is possible to use a cooled substrate. Cooling can take place by E~_ se known processes, such as by the introduction of cold inert gases or by contact with a cooling surface.
The hot melt pressure-sensitive adhesive can, for example, be applied in layer form or in individual areas, in accordance with a predetermined pattern, to the protective layer or the covering material. In a preferred embodiment, 133~688 the hot melt pressure-sensitive adhesive containing the substance or substances to be delivered is present in the form of one or more layers.
Depending upon the function of the intended use (and, e.g., if the substance to be released is to be released through the backing layer, such as can be the case with essential oils, such as fragrances), the hot melt pressure-sensitive adhesive may be finished with a carrier permeable with respect to the substance or substances to be released. However, in the embodiment of the device as a transdermal system, where the substance is only to be delivered to the skin, preference is given to a backing layer which is impermeable for the substance to be delivered.
In another preferred embodiment the device further comprises a removable protective layer.
The inventive process makes it possible to obviate the use of solvent-containing pressure-sensitive adhesive materials in the processing of temperature-sensitive, highly volatile substances. This significantly increases the safety of production since it is now certain that no toxic solvent residues can remain in the medicinal administration form. As well, the application process is greatly simplified and considerable cost savings in terms of production is achieved. Naturally, the process can also be used in an advantageous manner for less temperature-1~33688 sensitive substances as this also leads to considerable costsavings.
The term "substances" in connection with the present invention is understood to mean chemical elements, organic or inorganic compounds, which can migrate out of the components containing them in such a device and can thereby bring about a sought after effect. Among the uses of the inventive device particular significance is attached to human and veterinary medicine, a realization of the invention in plaster form being particularly preferred.
Typical substances which can be administered by means of the devices of invention include: aceclidine, amphetaminil, amphetamine, amylnitrite, apophedrin, atebrin, alprostadil, azulene, arecoline, anethole, amylenehydrate, acetylcholine, acridine, adenosintriphosphoric acid, L-malic acid, alimemazine, allithiamine, allyl isothiocyanate, amino-ethanol, apyzine, apiol, azatadine, alprenolol, ethinazone, benzoylperoxide, benzyl alcohol, bisabolol, bisnorephedrine, butacetoluid, benactyzine, campher, colecalciferol, choralhydrate, clemastine, chlorobutanol, capsaicin, cyclopentamine, clobutinol, chamazulene, cimethocaine, codeine, chloropromazine, quinine, chlorothymol, cyclophosphamide, cinchocaine, chlorambucil, chlorphenesin, diethylethane, divinylethane, dexchlorpheniramine, dinoprostone, dixyrazine, ephedrine, ethosuximide, enallylpropymal, emylcamate, erytroltetra-nitrate, emetine, enflurane, eucalyptol, etofenamate, ~J ' I33368~
ethylmorphine, fentanyl, fluanisone, guajazulene, holathane, hyoscyamine, histamine, fencarbamide, hydroxycaine, hexylresorcinol, isoaminlcitrate, isosorbidedinitrate, ibuprofin, iodine, iodoform, isoaminile, lidocaine, lopirine, levamisole, methadone, methyprylone, methyl-phenidate, mephenesine, methylephedrine, meclastine, methopromazine, mesuximide, nicethamide, norpseudoephedrine, menthosl, methoxyflurane, methylpentinol, metixen, misoprostol, oxytetracaine, oxyprenolol, oxyphenbutazone, oxyquinoline, pinene, prolintane, procylidine, piperazine, pivazide, phensuzimide, procaine, phenindamine, promethazine, pentetrazole, profenamine, perazine, phenol, pethidine, pilocarpine, prenylamine, phenoxybenzamine, resochin, scopolamine, salicylic acid ester, sparteine, trichloroethylene, timolol, trifluperazine, tetracaine, trimipramine, tranylcypromine, trimethadione, tybamate, thymol, thioridazine, valproic acid, verapamil, as well as other active substances which can be taken up through the skin. Obviously, this list is not exhaustive.
Typical compositions for the hot melt pressure-sensitive adhesives to be used are those prepared from between about 10 and 100% by weight, preferably about 20 to 80% by weight and in the particularly preferred manner about 20 to 50% by weight of polymer; between about 10 and 80% by weight, preferably about 15 to 60% by weight of plasticizer;
between about 10 and 80% by weight, preferably about 15 to 60% by weight of tackifier; and, optionally, about 0.1 to 5%
by weight of anti-agers and/or about 0 to 70% by weight of fillers; the sum of the percentages of the components always being 100.
Preferably, the hot melt pressure-sensitive adhesive contains 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 a hydrogenated alcohol, such as is commercially available under the name ABITOL~ from HERCULES; between about 10 and 80% by weight of a hydro-carbon 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, etc., as well as up to about 70% by weight of fillers.
In a further preferred embodiment of the invention the hot melt pressure-sensitive adhesive has 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 fillers.
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 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, etc., 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. LUPHEN 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 pressure-sensitive 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, -` 1333688 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 hydrogenated alcohol, e.g. ABITOL~ of HERCULES; between about 10 and 80% by weight of a hydro-carbon 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, such as hydroquinone, etc., as well as up to about 70% by weight of fillers.
Another hot melt pressure-sensitive adhesive operable in the production of the inventive transdermal systems has about 10 to 50% by weight of polyisobutine with a tacky, rubber-like consistency, such as e.g. OPPANOL B 50~
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.
Finally, it is preferred 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~ 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 devices of the invention may also contain one or more substance depots in which the substance is present in a higher concentration than the active substance-containing hot melt pressure-sensitive adhesive layer, so that higher substance doses can be processed and consequently the device can remain in use longer before it has to be changed. Typical constructions appear e.g. in DE-OS 36 29 304.
In drawings which illustrate embodiments of the invention, Figure 1 is a sectional view through the layers of a preferred device of invention with a substance depot;
Figure 2 is a sectional view through the layers of a further preferred device of the invention with an active substance depot: and Figure 3 is a sectional view through the layers of another embodiment of the inventive device without a substance depot.
With reference to Figure 1, a preferred embodiment of the device of the invention is shown which is in the form of a plaster-like, active substance-containing, transdermal, therapeutic system. It comprises a hot melt pressure-sensitive adhesive layer 12, an active substance depot 14 in which the active substance has a higher concentration than in the hot melt pressure-sensitive adhesive layer 12, as well as an active substance-impermeable carrier 10, on which rests the active substance depot 14 and which is affixed to the skin 18. Active substance continuously migrates at a predetermined rate through the skin 18 such that the active substance content of layer 12 decreases. The active substance decrease is compensated by an after-flow of active substance from the active substance depot 14, so that over a predetermined period of time there is an equilibrium concentration of the active substance in the hot melt pressure-sensitive adhesive layer 12, which ensures the delivery of a constance active substance quantity of the skin 18.
Referring now to Figure 2, another embodiment of the inventive device is shown, in which an active substance depot 14 is surrounded on all sides by the hot melt pressure-sensitive adhesive layer 12. This embodiment is particularly suitable if a large pressure-sensitive surface between the active substance depot and the hot melt pressure-sensitive adhesive layer is desired for a rapid active substance delivery to the hot melt pressure-sensitive adhesive layer.
With reference to Figure 3, a further embodiment of the inventive device is shown, in which an active substance-containing hot melt pressure-sensitive adhesive layer 12 is applied to an impermeable carrier material 10 in such a way that the latter covers the layer 12 on three sides. With the free hot melt pressure-sensitive adhesive surface it is affixed to the skin 18, so that a whole-area contact is ensured over the application time and the transfer of the active substance to the skin always takes place over a constant surface and at a constant speed.
The inventively improved production of the device of the invention will now be described. Firstly, the mixture of the components of the hot melt pressure-sensitive adhesive and the substance to be administered is prepared.
This mixture is then brought to the processing temperature and applied from the melt to a carrier material. The necessary further processing, such as the application of an adhesively finished protective layer material, may take place in the conventional manner.
Claims (19)
1. A device for the release of a substance from a hot melt pressure sensitive adhesive having a non-uniform or uniform distribution of the substances in the hot melt pressure sensitive adhesives, wherein a mixture of hot melt pressure sensitive adhesive and substance or a solution of the substance in the hot melt pressure sensitive adhesive is present, the hot melt pressure sensitive adhesive having a processing temperature between about 40 and 80°C.
2. A device as claimed in claim 1, wherein the processing temperature is between about 40 and 60°C.
3. A device as claimed in claim 1, wherein the processing temperature is between about 40 and 55°C.
4. A device as claimed in claim 1, 2 or 3, wherein the hot melt pressure-sensitive adhesive containing the substance or substances to be delivered is present in the form of one or more layers.
5. A device as claimed in claim 1, 2 or 3, wherein the hot melt pressure-sensitive adhesive is associated with a carrier which is permeable or impermeable for the substance or substances to be released.
6. A device as claimed in claim 1, wherein the hot melt pressure-sensitive adhesive is produced from at least one of styrene-isoprene-styrene block polymers, polycaprolactones, ethylene-vinyl acetate copolymers, polyurethane, polyepoxides, polyisobutene, or polyvinyl ethers, and, optionally, includes one or more of plasticizers, tackifiers, fillers, anti-agers and/or thixotropic agents.
7. A device as claimed in claim 6, wherein the hot melt pressure-sensitive adhesive is prepared from about 10 to 100% by weight of polymer, from about 10 to 80% by weight of plasticizer, from about 10 to 80% by weight of tackifier and, optionally, about 0.1 to 5% by weight of anti-ager and/or about 0 to 70% by weight of filler, the sum of the percentages of the components always being 100.
8. A device as claimed in claim 7, wherein from about 20 to 80% by weight of polymer is used to prepare the hot melt pressure-sensitive adhesive.
9. A device as claimed in claim 7, wherein from about 20 to 50% by weight of polymer is used to prepare the hot melt pressure-sensitive adhesive.
10. A device as claimed in claim 7, wherein from about 15 to 60% by weight of plasticizer is used to prepare the hot melt pressure-sensitive adhesive.
11. A device as claimed in claim 7, wherein from about 15 to 60% by weight of tackifier is used to prepare the hot melt pressure-sensitive adhesive.
12. A device as claimed in any one of claims 1 to 11, wherein the apparatus further comprises a removable protective layer.
13. A process for the production of a device for the release of a substance from a hot melt pressure-sensitive adhesive, which comprises continuously or discontinuously applying a molten mixture of hot melt pressure-sensitive adhesive and the substance to be released at a hot melt pressure-sensitive temperature between about 40 and 80°C, to a carrier, and optionally applying a protective layer material.
14. A process for the production of a device for the release of a substance from a hot melt pressure-sensitive adhesive, which comprises continuously or discontinuously applying to a protective layer material a molten mixture of hot melt pressure-sensitive adhesive, and the substance to be released at a hot melt pressure-sensitive adhesive temperature between about 40 and 80°C
and optionally applying a carrier.
and optionally applying a carrier.
15. A process as claimed in claim 13 or 14, wherein the hot melt pressure-sensitive adhesive temperature is between about 40 and 60°C.
16. A process as claimed in claim 13 or 14, wherein the hot melt pressure-sensitive adhesive temperature is between about 40 and 55°C.
17. A process as claimed in claim 13 or 14, wherein the formation of the components of the apparatus is effected by extrusion, pouring, roller application, knife coating, spraying or a printing process.
18. A device as claimed in claim 1, 2, 3, 6, 7, 8, 9, 10 or 11, for use in human and veterinary medicine, diagnostics or cosmetics.
19. A device as claimed in claim 1, 2, 3, 6, 7, 8, 9, 10 or 11, for the delivery of temperature-sensitive and/or highly volatile substances in human or veterinary medicine, diagnostics or cosmetics.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP3729165.3 | 1987-09-01 | ||
| DE3729165 | 1987-09-01 | ||
| DE19873743945 DE3743945A1 (en) | 1987-09-01 | 1987-12-23 | DEVICE FOR DELIVERING SUBSTANCES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE |
| DEP3743945.6 | 1987-12-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1333688C true CA1333688C (en) | 1994-12-27 |
Family
ID=25859260
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000575201A Expired - Lifetime CA1333688C (en) | 1987-09-01 | 1988-08-19 | Device for the delivery of substances, process for the production thereof and use thereof |
Country Status (23)
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|---|---|
| EP (1) | EP0305756B1 (en) |
| JP (1) | JP2781579B2 (en) |
| KR (1) | KR970006448B1 (en) |
| AT (1) | ATE83655T1 (en) |
| AU (1) | AU636835B2 (en) |
| CA (1) | CA1333688C (en) |
| CZ (1) | CZ281743B6 (en) |
| DE (2) | DE3743945A1 (en) |
| DK (1) | DK175442B1 (en) |
| ES (1) | ES2036242T3 (en) |
| FI (1) | FI96577C (en) |
| GR (1) | GR3006666T3 (en) |
| HU (1) | HU205268B (en) |
| IE (1) | IE62943B1 (en) |
| IL (1) | IL87538A (en) |
| MY (1) | MY103757A (en) |
| NO (1) | NO178684C (en) |
| NZ (1) | NZ225918A (en) |
| PL (1) | PL163710B1 (en) |
| PT (1) | PT88378B (en) |
| SK (1) | SK587388A3 (en) |
| WO (1) | WO1989001787A1 (en) |
| YU (1) | YU47201B (en) |
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| US4564364A (en) * | 1983-05-26 | 1986-01-14 | Alza Corporation | Active agent dispenser |
| ATE95430T1 (en) * | 1984-12-22 | 1993-10-15 | Sanol Arznei Schwarz Gmbh | ACTIVE PATCHES. |
| DE3629304A1 (en) * | 1986-08-28 | 1988-03-24 | Lohmann Gmbh & Co Kg | TRANSDERMAL THERAPEUTIC SYSTEM, ITS USE AND METHOD FOR THE PRODUCTION THEREOF |
| JPH0816053B2 (en) * | 1986-12-04 | 1996-02-21 | 大正製薬株式会社 | Method of manufacturing patch |
| DE3743946A1 (en) * | 1987-09-01 | 1989-03-09 | Lohmann Gmbh & Co Kg | DEVICE FOR DELIVERING NITROGLYCERIN TO THE SKIN, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE |
-
1987
- 1987-12-23 DE DE19873743945 patent/DE3743945A1/en active Granted
-
1988
- 1988-08-03 ES ES198888112630T patent/ES2036242T3/en not_active Expired - Lifetime
- 1988-08-03 EP EP88112630A patent/EP0305756B1/en not_active Expired - Lifetime
- 1988-08-03 AT AT88112630T patent/ATE83655T1/en not_active IP Right Cessation
- 1988-08-03 JP JP63506544A patent/JP2781579B2/en not_active Expired - Lifetime
- 1988-08-03 AU AU22506/88A patent/AU636835B2/en not_active Ceased
- 1988-08-03 WO PCT/DE1988/000477 patent/WO1989001787A1/en active IP Right Grant
- 1988-08-03 KR KR1019890700772A patent/KR970006448B1/en not_active IP Right Cessation
- 1988-08-03 DE DE8888112630T patent/DE3876898D1/en not_active Expired - Lifetime
- 1988-08-03 HU HU884702A patent/HU205268B/en not_active IP Right Cessation
- 1988-08-10 MY MYPI88000912A patent/MY103757A/en unknown
- 1988-08-19 CA CA000575201A patent/CA1333688C/en not_active Expired - Lifetime
- 1988-08-22 IE IE255488A patent/IE62943B1/en not_active IP Right Cessation
- 1988-08-23 IL IL8753888A patent/IL87538A/en not_active IP Right Cessation
- 1988-08-24 NZ NZ225918A patent/NZ225918A/en unknown
- 1988-08-31 CZ CS885873A patent/CZ281743B6/en not_active IP Right Cessation
- 1988-08-31 SK SK5873-88A patent/SK587388A3/en unknown
- 1988-08-31 PT PT88378A patent/PT88378B/en not_active IP Right Cessation
- 1988-09-01 PL PL88274486A patent/PL163710B1/en unknown
- 1988-09-01 YU YU166288A patent/YU47201B/en unknown
-
1989
- 1989-04-12 NO NO891507A patent/NO178684C/en unknown
- 1989-04-28 DK DK198902102A patent/DK175442B1/en not_active IP Right Cessation
- 1989-04-28 FI FI892053A patent/FI96577C/en not_active IP Right Cessation
-
1992
- 1992-12-24 GR GR920403040T patent/GR3006666T3/el unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7847014B2 (en) * | 2001-04-12 | 2010-12-07 | Lts Lohmann Therapie-Systeme Ag | Adhesive emulsion for medical purposes made from ethylene-vinyl acetate copolymers and adhesive resins |
| US8246982B2 (en) | 2001-04-12 | 2012-08-21 | Lts Lohmann Therapie-Systeme Ag | Pressure-sensitive adhesives based on ethylene-vinyl acetate copolymers and adhesive resins, for medical application purposes |
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| Date | Code | Title | Description |
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| MKEX | Expiry |