CA2210341A1 - Transdermal therapeutic system for dispensing (s)-3-methyl-5-(1-methyl-2-pyrrolidenyl)-isoxazole or one of its pharmaceutically acceptable salts - Google Patents
Transdermal therapeutic system for dispensing (s)-3-methyl-5-(1-methyl-2-pyrrolidenyl)-isoxazole or one of its pharmaceutically acceptable saltsInfo
- Publication number
- CA2210341A1 CA2210341A1 CA002210341A CA2210341A CA2210341A1 CA 2210341 A1 CA2210341 A1 CA 2210341A1 CA 002210341 A CA002210341 A CA 002210341A CA 2210341 A CA2210341 A CA 2210341A CA 2210341 A1 CA2210341 A1 CA 2210341A1
- Authority
- CA
- Canada
- Prior art keywords
- administration form
- form according
- active substance
- methyl
- matrix
- 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.)
- Abandoned
Links
- 150000003839 salts Chemical class 0.000 title claims abstract description 8
- 230000001225 therapeutic effect Effects 0.000 title claims abstract description 5
- 239000013543 active substance Substances 0.000 claims description 38
- 239000010410 layer Substances 0.000 claims description 14
- 229920000642 polymer Polymers 0.000 claims description 12
- 239000011159 matrix material Substances 0.000 claims description 10
- 239000011241 protective layer Substances 0.000 claims description 9
- 239000004820 Pressure-sensitive adhesive Substances 0.000 claims description 8
- 239000012528 membrane Substances 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 239000004744 fabric Substances 0.000 claims description 4
- 239000004014 plasticizer Substances 0.000 claims description 4
- 239000004753 textile Substances 0.000 claims description 4
- 230000009974 thixotropic effect Effects 0.000 claims description 4
- 229920001577 copolymer Polymers 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 230000007246 mechanism Effects 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- -1 polyoxyethylene Polymers 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 2
- 229920000058 polyacrylate Polymers 0.000 claims description 2
- 150000003097 polyterpenes Chemical class 0.000 claims description 2
- 239000003961 penetration enhancing agent Substances 0.000 claims 6
- 239000004831 Hot glue Substances 0.000 claims 3
- 150000002148 esters Chemical class 0.000 claims 3
- 150000001298 alcohols Chemical class 0.000 claims 2
- 150000001412 amines Chemical class 0.000 claims 2
- 150000001735 carboxylic acids Chemical class 0.000 claims 2
- 150000002170 ethers Chemical class 0.000 claims 2
- 229930195733 hydrocarbon Natural products 0.000 claims 2
- 150000002430 hydrocarbons Chemical class 0.000 claims 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims 1
- 229920002367 Polyisobutene Polymers 0.000 claims 1
- 238000005266 casting Methods 0.000 claims 1
- 238000001125 extrusion Methods 0.000 claims 1
- 150000002314 glycerols Chemical class 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 claims 1
- 150000004040 pyrrolidinones Chemical class 0.000 claims 1
- 238000007761 roller coating Methods 0.000 claims 1
- 229930004725 sesquiterpene Natural products 0.000 claims 1
- 150000004354 sesquiterpene derivatives Chemical class 0.000 claims 1
- 229920003051 synthetic elastomer Polymers 0.000 claims 1
- 239000005061 synthetic rubber Substances 0.000 claims 1
- 238000010345 tape casting Methods 0.000 claims 1
- 150000003626 triacylglycerols Chemical class 0.000 claims 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims 1
- 239000011505 plaster Substances 0.000 abstract 1
- 210000004379 membrane Anatomy 0.000 description 6
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 4
- 239000000654 additive Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- 230000001270 agonistic effect Effects 0.000 description 2
- 229920005601 base polymer Polymers 0.000 description 2
- 230000036765 blood level Effects 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 230000000474 nursing effect Effects 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 229920002126 Acrylic acid copolymer Polymers 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 229920000298 Cellophane Polymers 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000036626 alertness Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000005755 formation reaction Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
- 125000005397 methacrylic acid ester group Chemical group 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 239000005033 polyvinylidene chloride Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
Classifications
-
- 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
- A61K9/703—Transdermal 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
- A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
An administration form for dispensing (s)-3-methyl-5-(1-methyl-2-pyrrolidenyl)-isoxazole or one of its pharmaceutically acceptable salts is characterized in that it is a transdermal therapeutic system having the form of a plaster.
Description
, . CA 02210341 1997-07-14 A transdermal therapeutic system for the administration of (s)-3-methyl-5-(1-methyl-2-pyrrolidenyl)-isoxazole or one of its pharmaceutically acceptable salts S P E C I F I C A T I O N
The present invention relates to an administration form for the administration of (s)-3-methyl-5~ methyl-2-pyrrolidenyl)-isoxazole or one of its pharmaceutically acceptable salts and to a process for its production.
The active substance (s)-3-methyl-5-(1-methyl-2-pyrrolidenyl)-isoxazole stands out for a highly specific agonistic effect on the choliIlergic nervous system, in particular on the nicotinic re-ceptors. Based on recent studies of the Alzheimer's disease ther-apy, the application of this active substance seems to improve the cogni~ive abilities of diseased persons to a considerable extent. In this connection, however, regular and quantitatively constant ad-ministration of the active substance is an important factor to en-sure constantly effective blood levels over extended periods. So far the active substance has been administered exclusively by the oral route. However, the oral administration of drugs to patients suffering from dementia imposes unacceptable requirements on the nursing staff, since the patient - owing to his disease - is not able lio control the intake on his own.
It is the object of the present invention to provide an administra-tion form for the administration of the active substance (s)-3-methyl-5-(1-methyl-2-pyrrolidenyl)-isoxazole to achieve a highly specific agonistic effect on the cholinergic nervous system of patielllts suffering from dementia. Replacing the hitherto required regular oral administration at short intervals, it can achieve a con-stantly effective blood level and - for the patients' well-being -relieves the nursing staff from the burden and alertness experi-enced as a disadvantage so far.
To achieve this object the present invention provides a new ad-ministration form to administer (s)-3-methyl-5- (1-methyl-2-pyr-rolidenyl)-isoxazole or one of its pharmaceutically acceptable salts, which consists in the fact that it is present in the form of a patch as a transdermal therapeutic system (TTS).
Accordingly, the subject matter of the present invention is a TTS
for the administration of (s)-3-methyl-5- (1-methyl-2-pyrrolidenyl)-isoxazole or one of its pharmaceutically acceptable salts, which is present in the form of a patch and comprises a suitable backing layer, an active substance reservoir connected thereto, a mem-brane controlling the active substance release if other control mechanisms are absent, a pressure-sensitive adhesive facility to fix the system to the skin, and, if required, a protective layer re-movable prior to the application of the system.
The suitable backing layer may consist both of a flexible and in-flexible material which is impermeable to active substances. Sub-stances suitable for its production include polymeric sheets or metallic foils, such as aluminum foils which may be used alone or coated with a polymeric substrate. In addition, textile fabrics may also Ibe used if the reservoir cannot penetrate through them owing to their physical property, or if penetration is prevented by an ade-quate layer.
The active substance reservoir may have either a layered or a bag-type structure.
The layered reservoir may optionally consist of a polymeric matrix and the pure active substance or of a suitable active substance formulation, wherein the cohesion of the system as such is , , ~ CA 02210341 1997-07-14 provided by the polymer properties. The reservoir consists of a base polymer and conventional additives. The choice of the poly-mer matrix and the base polymer depends on the physicochemical properties of the active substance on the one hand, and on the desired release from the system on the other hand. In principle, any polymer is suitable that is used in the production of pressure-sensitive adhesives and which is compatible with the active sub-stance. Examples thereof include: rubber, rubber-like homo-, co-, or block polymers, polyacrylates and their copolymers. Particularly preferred are those based on styrene and 1 ,3-dienes, polyisobu-tylenes and polyterpenes, or polymers based on conventional acrylate monomers and their derivatives. Among the block poly-mers based on styrene and 1,3-dienes linear styrene-isoprene-bloclc-polymers are preferably used. Preferred polymers based on acrylate are acrylic acid copolymers of 2-ethylhexyl acrylate, vinyl acetate and acrylic acid with or without cross-linking agents.
Methacrylates are primarily understood as copolymers based on dime~hylaminomethacrylate and neutral methacrylic acid esters with or without cross-linking agents.
The klnd and amount of possible additives depends on the polymer matrix used and on the active substance. According to their func-tion they may be classified into the following groups: plasticizers, tackifiers, stabilizers, carrier substances, diffusion and penetration regulating additives, or fillers. The physiologically acceptable sub-stances suitable for this purpose are known to pharmacists.
A bag-type reservoir system may consist of the pure active sub-stance or of a highly viscous or semisolid or thixotropic active substance preparation. Particularly suitable are oily or aqueous gels which are dosed into a bag made of suitable sheetings or membrane materials. In this connection, production of the active substance preparation may be carried out on the basis of lipo-philic or hydrophilic bases. In this case, the back of the bag, which is averted . ~ CA 02210341 1997-07-14 from the skin,must be impermeable to the active substance, and the side facing the skin must be permeable to the active sub-stance. Preferably, a membrane which is permeable to the active substance can control the active substance release.
In the absence of other control mechanisms, the reservoir may be combined with a membrane controlling the active substance re-lease and a pressure-sensitive adhesive device to fix the system to the skin. A reservoir not sufficiently adhering to the skin repre-sents a particular case; this is combined with a special pressure-sensitive adhesive layer ensuring permanent contact of the system to the skin. In principle, the same materials as those used for the polymer matrix of the reservoir are suitable for the pressure-sensi-tive adhesive facility.
The protective layer which, if required, is to be removed prior to application may consist of the same materials as those used for the backing layer of the system provided that they have been ren-dered removable, e.g., by a silicone treatment. However, it is also possible to use other protective layers, such as paper treated with polytetrafluoroethylene, cellophane, polyvinyl chloride, polyvinyl-idene chloride, and the like. If the laminate according to the pres-ent invention is divided into formats adequate for therapy (patc,hes) prior to application of the protective layer, the formats of the protective layer to be applied then may have a projecting end to make their removal from the patch easier.
In accordance with the layered or bag-type construction of the transdermal systems described hereinabove, two different produc-tion processes are described:
a: The active substance is homogeneously mixed with the compo-nents of the active substance reservoir, optionally in solution or under heating and cooling, and applied to the cover layer which is - . CA 02210341 1997-07-14 permeable to the active substances or to a textile fabric Iying thereon, whereupon the solvent/s is/are removed, if necessary.
Depending on whether the reservoir layer is self-adhesive or not, a pressure-sensitive adhesive device for permanent attachment to the skin is introduced between the reservoir and the protective layer which is removed in case of need.
b~ 'ithin an adequate device, the liquid active substance or the liquid or semisolid or thixotropic active substance formulation is dose!d onto a membrane which is permeable to the active sub-stanoe and covered with a suitable sheeting, avoiding the forma-tion of voids as far as possible, whereupon the membrane and the sheeting are tightly sealed to form a bag. Optionally, dosage may be carried out into a textile fabric which can additionally serve as a support. It is also possible to dose into preformed bags. The res-ervoir bag filled with active substance is additionally combined with a pressure-sensitive adhesive device, which may also have a multilayered structure and be provided with a control function for active substance release, and is subsequently covered with a protective layer which is removed in case of need.
The present invention relates to an administration form for the administration of (s)-3-methyl-5~ methyl-2-pyrrolidenyl)-isoxazole or one of its pharmaceutically acceptable salts and to a process for its production.
The active substance (s)-3-methyl-5-(1-methyl-2-pyrrolidenyl)-isoxazole stands out for a highly specific agonistic effect on the choliIlergic nervous system, in particular on the nicotinic re-ceptors. Based on recent studies of the Alzheimer's disease ther-apy, the application of this active substance seems to improve the cogni~ive abilities of diseased persons to a considerable extent. In this connection, however, regular and quantitatively constant ad-ministration of the active substance is an important factor to en-sure constantly effective blood levels over extended periods. So far the active substance has been administered exclusively by the oral route. However, the oral administration of drugs to patients suffering from dementia imposes unacceptable requirements on the nursing staff, since the patient - owing to his disease - is not able lio control the intake on his own.
It is the object of the present invention to provide an administra-tion form for the administration of the active substance (s)-3-methyl-5-(1-methyl-2-pyrrolidenyl)-isoxazole to achieve a highly specific agonistic effect on the cholinergic nervous system of patielllts suffering from dementia. Replacing the hitherto required regular oral administration at short intervals, it can achieve a con-stantly effective blood level and - for the patients' well-being -relieves the nursing staff from the burden and alertness experi-enced as a disadvantage so far.
To achieve this object the present invention provides a new ad-ministration form to administer (s)-3-methyl-5- (1-methyl-2-pyr-rolidenyl)-isoxazole or one of its pharmaceutically acceptable salts, which consists in the fact that it is present in the form of a patch as a transdermal therapeutic system (TTS).
Accordingly, the subject matter of the present invention is a TTS
for the administration of (s)-3-methyl-5- (1-methyl-2-pyrrolidenyl)-isoxazole or one of its pharmaceutically acceptable salts, which is present in the form of a patch and comprises a suitable backing layer, an active substance reservoir connected thereto, a mem-brane controlling the active substance release if other control mechanisms are absent, a pressure-sensitive adhesive facility to fix the system to the skin, and, if required, a protective layer re-movable prior to the application of the system.
The suitable backing layer may consist both of a flexible and in-flexible material which is impermeable to active substances. Sub-stances suitable for its production include polymeric sheets or metallic foils, such as aluminum foils which may be used alone or coated with a polymeric substrate. In addition, textile fabrics may also Ibe used if the reservoir cannot penetrate through them owing to their physical property, or if penetration is prevented by an ade-quate layer.
The active substance reservoir may have either a layered or a bag-type structure.
The layered reservoir may optionally consist of a polymeric matrix and the pure active substance or of a suitable active substance formulation, wherein the cohesion of the system as such is , , ~ CA 02210341 1997-07-14 provided by the polymer properties. The reservoir consists of a base polymer and conventional additives. The choice of the poly-mer matrix and the base polymer depends on the physicochemical properties of the active substance on the one hand, and on the desired release from the system on the other hand. In principle, any polymer is suitable that is used in the production of pressure-sensitive adhesives and which is compatible with the active sub-stance. Examples thereof include: rubber, rubber-like homo-, co-, or block polymers, polyacrylates and their copolymers. Particularly preferred are those based on styrene and 1 ,3-dienes, polyisobu-tylenes and polyterpenes, or polymers based on conventional acrylate monomers and their derivatives. Among the block poly-mers based on styrene and 1,3-dienes linear styrene-isoprene-bloclc-polymers are preferably used. Preferred polymers based on acrylate are acrylic acid copolymers of 2-ethylhexyl acrylate, vinyl acetate and acrylic acid with or without cross-linking agents.
Methacrylates are primarily understood as copolymers based on dime~hylaminomethacrylate and neutral methacrylic acid esters with or without cross-linking agents.
The klnd and amount of possible additives depends on the polymer matrix used and on the active substance. According to their func-tion they may be classified into the following groups: plasticizers, tackifiers, stabilizers, carrier substances, diffusion and penetration regulating additives, or fillers. The physiologically acceptable sub-stances suitable for this purpose are known to pharmacists.
A bag-type reservoir system may consist of the pure active sub-stance or of a highly viscous or semisolid or thixotropic active substance preparation. Particularly suitable are oily or aqueous gels which are dosed into a bag made of suitable sheetings or membrane materials. In this connection, production of the active substance preparation may be carried out on the basis of lipo-philic or hydrophilic bases. In this case, the back of the bag, which is averted . ~ CA 02210341 1997-07-14 from the skin,must be impermeable to the active substance, and the side facing the skin must be permeable to the active sub-stance. Preferably, a membrane which is permeable to the active substance can control the active substance release.
In the absence of other control mechanisms, the reservoir may be combined with a membrane controlling the active substance re-lease and a pressure-sensitive adhesive device to fix the system to the skin. A reservoir not sufficiently adhering to the skin repre-sents a particular case; this is combined with a special pressure-sensitive adhesive layer ensuring permanent contact of the system to the skin. In principle, the same materials as those used for the polymer matrix of the reservoir are suitable for the pressure-sensi-tive adhesive facility.
The protective layer which, if required, is to be removed prior to application may consist of the same materials as those used for the backing layer of the system provided that they have been ren-dered removable, e.g., by a silicone treatment. However, it is also possible to use other protective layers, such as paper treated with polytetrafluoroethylene, cellophane, polyvinyl chloride, polyvinyl-idene chloride, and the like. If the laminate according to the pres-ent invention is divided into formats adequate for therapy (patc,hes) prior to application of the protective layer, the formats of the protective layer to be applied then may have a projecting end to make their removal from the patch easier.
In accordance with the layered or bag-type construction of the transdermal systems described hereinabove, two different produc-tion processes are described:
a: The active substance is homogeneously mixed with the compo-nents of the active substance reservoir, optionally in solution or under heating and cooling, and applied to the cover layer which is - . CA 02210341 1997-07-14 permeable to the active substances or to a textile fabric Iying thereon, whereupon the solvent/s is/are removed, if necessary.
Depending on whether the reservoir layer is self-adhesive or not, a pressure-sensitive adhesive device for permanent attachment to the skin is introduced between the reservoir and the protective layer which is removed in case of need.
b~ 'ithin an adequate device, the liquid active substance or the liquid or semisolid or thixotropic active substance formulation is dose!d onto a membrane which is permeable to the active sub-stanoe and covered with a suitable sheeting, avoiding the forma-tion of voids as far as possible, whereupon the membrane and the sheeting are tightly sealed to form a bag. Optionally, dosage may be carried out into a textile fabric which can additionally serve as a support. It is also possible to dose into preformed bags. The res-ervoir bag filled with active substance is additionally combined with a pressure-sensitive adhesive device, which may also have a multilayered structure and be provided with a control function for active substance release, and is subsequently covered with a protective layer which is removed in case of need.
Claims (21)
1. An administration form for the administration of (s)-3-methyl-5-(1-methyl-2-pyrrolidenyl)-isoxazole or one of its pharmaceutically acceptable salts characterized in that it is present as a transdermal therapeutic system in the form of a patch.
2. The administration form according to claim 1 characterized in that it comprises a suitable backing layer, an active substance reservoir laminated thereon, in the absence of other control mechanisms, a membrane controlling the active substance release, a pressure-sensitive adhesive device to attach the system to the skin, and, if required, a protective layer removable prior to application.
3. The administration form according to claim 1 characterized in that the backing layer of the system is impermeable to moisture and active substance.
4. The administration form according to claim 1 characterized in that the backing layer is permeable to the active substance.
5. The administration form according to one or several of the preceding claims characterized in that it has a layered structure with at least one polymer layer.
6. The administration form according to claim 5 characterized in that the material of the polymer layer is selected from the groups of polyacrylates and their copolymers, polyisobutylenes, polyterpenes, ethylene-vinyl-acetate-copolymers, block polymers, synthetic rubbers, or hot-melt adhesives.
7. The administration form according to claim 5 characterized in that the polymer layer comprises esters of the hydrogenated colophony, in particular methyl or glycerol esters of hydrogenated colophony.
8. The administration form according to one or several of claims 1 - 7 characterized in that it comprises a plasticizer in a concentration of 0-30%, preferably 5-20%, relative to the total weight of the matrix.
9. The administration form according to claim 8 characterized in that the plasticizer comprises at least one component selected from the groups of hydrocarbons, alcohols, carboxylic acids and their derivatives, ethers, esters, or amines.
10. The administration form according to claim 8 characterized in that the plasticizer comprises a natural or partially synthetic triglyceride or a mixture of these triglycerides in a concentration ranging from 0- 30%, preferably in the range of 5 - 20%, relative to the total weight of the matrix.
11. The administration form according to one or several of the preceding claims characterized in that it comprises a permeation enhancer in a concentration ranging from 0 - 30%, preferably in the range of 5 - 20%, relative to the total weight of the matrix.
12. The administration form according to claim 11 characterized in that the permeation enhancer comprises at least one component selected from the groups of hydrocarbons, alcohols, carboxylic acids and their derivatives, ethers, esters, or amines.
13. The administration form according to claim 11 characterized in that the permeation enhancer comprises at least one component selected from the group consisting of mono-, di- or sesquiterpenes.
14. The administration form according to claim 11 characterized in that the permeation enhancer comprises at least one component selected from the group consisting of polyoxyethylene derivatives.
15. The administration form according to claim 11 characterized in that the permeation enhancer comprises a component selected from the group consisting of nitrogen-containing heterocycles and their derivatives.
16. The administration form according to claim 11 characterized in that the permeation enhancer comprises a component selected from the group consisting of pyrrolidone derivatives.
17. The administration form according to one or several of the preceding claims characterized in that it has a bag-type active substance reservoir filled with a liquid or semisolid or thixotropic matrix.
18. The administration form according to claim 17 characterized in that a gel former is the base of the semisolid or thixotropic active substance reservoir.
19. A process for the production of the administration form according to one or several of the preceding claims characterized in that (s)-3-methyl-5- (1-methyl-2-pyrrolidenyl)-isoxazole or its pharmaceutically acceptable salt is applied in solution on a textile fabric provided on a prefabricated matrix which is optionally provided with a protective layer, whereupon matrix and active substance depot are provided with a cover layer.
20. The process according to claim 19 characterized in that components of a hot-melt adhesive are incorporated, prior to the addition of the active substance, under heating to preferably 110 - 170°C until a homogeneous melt of 70 to 100°C is obtained.
21. The process according to claim 19 or 20 characterized in that the homogeneous, active-substance-containing hot-melt adhesive mass is applied by means of extrusion, casting, roller coating, knife coating, or by a printing process.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19501022A DE19501022C1 (en) | 1995-01-14 | 1995-01-14 | Transdermal therapeutic system for the administration of (s) -3-methyl-5- (1-methyl-2-pyrrolidenyl) isoxazole or one of its pharmaceutically acceptable salts and process for its preparation |
| DE19501022.1 | 1995-01-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2210341A1 true CA2210341A1 (en) | 1996-07-18 |
Family
ID=7751534
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002210341A Abandoned CA2210341A1 (en) | 1995-01-14 | 1996-01-10 | Transdermal therapeutic system for dispensing (s)-3-methyl-5-(1-methyl-2-pyrrolidenyl)-isoxazole or one of its pharmaceutically acceptable salts |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP0802790B1 (en) |
| JP (1) | JPH10511972A (en) |
| KR (1) | KR19980701419A (en) |
| AR (1) | AR001070A1 (en) |
| AT (1) | ATE292458T1 (en) |
| BR (1) | BR9607488A (en) |
| CA (1) | CA2210341A1 (en) |
| DE (2) | DE19501022C1 (en) |
| IL (1) | IL116615A (en) |
| NZ (1) | NZ298428A (en) |
| WO (1) | WO1996021434A1 (en) |
| ZA (1) | ZA96260B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9615628D0 (en) * | 1996-07-25 | 1996-09-04 | Smithkline Beecham Plc | Formulation |
| DE10004790B4 (en) * | 2000-02-01 | 2004-09-09 | Lts Lohmann Therapie-Systeme Ag | Method for producing sewn or embroidered three-dimensional textile structure utilized for e.g. table cloth, involves connecting points on lattice structure with threads to form thread arrangement under which lattice structure is not visible |
| DE10019067C1 (en) * | 2000-04-18 | 2001-10-04 | Lohmann Therapie Syst Lts | Transdermal plaster comprising dofetilide, is useful for treatment of cardiovascular disorders |
| DE10118282A1 (en) | 2001-04-12 | 2002-12-05 | Lohmann Therapie Syst Lts | Pressure sensitive adhesive based on ethylene-vinyl acetate copolymers and adhesive resins, for medical purposes |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE197454T1 (en) * | 1991-05-29 | 2000-11-11 | Abbott Lab | ISOXAZOLE AND ISOTHIAZOLE COMPOUNDS THAT IMPROVE COGNITIVE FUNCTIONS |
| DE4313928C2 (en) * | 1993-04-28 | 1996-09-19 | Lohmann Therapie Syst Lts | Transdermal therapeutic system for the controlled delivery of pilocarpine to the skin, process for its production and its use |
| DE4336557C2 (en) * | 1993-05-06 | 1997-07-17 | Lohmann Therapie Syst Lts | Estradiol-containing transdermal therapeutic system, process for its preparation and its use |
| US5494680A (en) * | 1993-12-08 | 1996-02-27 | Minnesota Mining And Manufacturing Company | Transdermal delivery device |
-
1995
- 1995-01-14 DE DE19501022A patent/DE19501022C1/en not_active Expired - Fee Related
- 1995-12-29 IL IL11661595A patent/IL116615A/en not_active IP Right Cessation
-
1996
- 1996-01-10 WO PCT/EP1996/000074 patent/WO1996021434A1/en active IP Right Grant
- 1996-01-10 KR KR1019970704809A patent/KR19980701419A/en active IP Right Grant
- 1996-01-10 NZ NZ298428A patent/NZ298428A/en unknown
- 1996-01-10 DE DE59611212T patent/DE59611212D1/en not_active Expired - Fee Related
- 1996-01-10 JP JP8521426A patent/JPH10511972A/en not_active Ceased
- 1996-01-10 AT AT96900309T patent/ATE292458T1/en not_active IP Right Cessation
- 1996-01-10 EP EP96900309A patent/EP0802790B1/en not_active Expired - Lifetime
- 1996-01-10 CA CA002210341A patent/CA2210341A1/en not_active Abandoned
- 1996-01-10 BR BR9607488A patent/BR9607488A/en not_active Application Discontinuation
- 1996-01-12 AR AR33502496A patent/AR001070A1/en unknown
- 1996-01-12 ZA ZA96260A patent/ZA96260B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AR001070A1 (en) | 1997-09-24 |
| EP0802790A1 (en) | 1997-10-29 |
| DE19501022C1 (en) | 1996-06-05 |
| KR19980701419A (en) | 1998-05-15 |
| ZA96260B (en) | 1996-08-01 |
| WO1996021434A1 (en) | 1996-07-18 |
| BR9607488A (en) | 1997-12-23 |
| DE59611212D1 (en) | 2005-05-12 |
| JPH10511972A (en) | 1998-11-17 |
| MX9705324A (en) | 1997-10-31 |
| EP0802790B1 (en) | 2005-04-06 |
| IL116615A0 (en) | 1996-03-31 |
| NZ298428A (en) | 1999-10-28 |
| ATE292458T1 (en) | 2005-04-15 |
| IL116615A (en) | 1999-09-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued | ||
| FZDE | Discontinued |
Effective date: 20050110 |