SK149797A3 - Transdermal therapeutic system (tts) for administering testosterone - Google Patents
Transdermal therapeutic system (tts) for administering testosterone Download PDFInfo
- Publication number
- SK149797A3 SK149797A3 SK1497-97A SK149797A SK149797A3 SK 149797 A3 SK149797 A3 SK 149797A3 SK 149797 A SK149797 A SK 149797A SK 149797 A3 SK149797 A3 SK 149797A3
- Authority
- SK
- Slovakia
- Prior art keywords
- active ingredient
- testosterone
- carrier
- adhesive
- release
- Prior art date
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- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 title claims abstract description 30
- 229960003604 testosterone Drugs 0.000 title claims abstract description 16
- 230000001225 therapeutic effect Effects 0.000 title claims abstract description 16
- 150000003515 testosterones Chemical class 0.000 claims abstract description 8
- 239000013543 active substance Substances 0.000 claims abstract description 4
- 239000004480 active ingredient Substances 0.000 claims description 41
- 239000000853 adhesive Substances 0.000 claims description 26
- 230000001070 adhesive effect Effects 0.000 claims description 22
- 239000012528 membrane Substances 0.000 claims description 17
- -1 testosterone ester Chemical class 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 239000012790 adhesive layer Substances 0.000 claims description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 9
- 229920001296 polysiloxane Polymers 0.000 claims description 8
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 6
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 5
- 229920000858 Cyclodextrin Polymers 0.000 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 4
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 4
- PDMMFKSKQVNJMI-BLQWBTBKSA-N Testosterone propionate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CC)[C@@]1(C)CC2 PDMMFKSKQVNJMI-BLQWBTBKSA-N 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 229960003484 testosterone enanthate Drugs 0.000 claims description 3
- VOCBWIIFXDYGNZ-IXKNJLPQSA-N testosterone enanthate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCCCC)[C@@]1(C)CC2 VOCBWIIFXDYGNZ-IXKNJLPQSA-N 0.000 claims description 3
- 229960001712 testosterone propionate Drugs 0.000 claims description 3
- 229960000746 testosterone undecanoate Drugs 0.000 claims description 3
- UDSFVOAUHKGBEK-CNQKSJKFSA-N testosterone undecanoate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCCCCCCCC)[C@@]1(C)CC2 UDSFVOAUHKGBEK-CNQKSJKFSA-N 0.000 claims description 3
- GCKMFJBGXUYNAG-UHFFFAOYSA-N 17alpha-methyltestosterone Natural products C1CC2=CC(=O)CCC2(C)C2C1C1CCC(C)(O)C1(C)CC2 GCKMFJBGXUYNAG-UHFFFAOYSA-N 0.000 claims description 2
- 239000001116 FEMA 4028 Substances 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 claims description 2
- GCKMFJBGXUYNAG-HLXURNFRSA-N Methyltestosterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)CC2 GCKMFJBGXUYNAG-HLXURNFRSA-N 0.000 claims description 2
- 229940087168 alpha tocopherol Drugs 0.000 claims description 2
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 2
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 2
- 229960004853 betadex Drugs 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 229960001566 methyltestosterone Drugs 0.000 claims description 2
- 239000003961 penetration enhancing agent Substances 0.000 claims description 2
- 229920002635 polyurethane Polymers 0.000 claims description 2
- 239000004814 polyurethane Substances 0.000 claims description 2
- 229920001289 polyvinyl ether Polymers 0.000 claims description 2
- HPFVBGJFAYZEBE-ZLQWOROUSA-N testosterone cypionate Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(CCC(=O)C=C4CC3)C)CC[C@@]21C)C(=O)CCC1CCCC1 HPFVBGJFAYZEBE-ZLQWOROUSA-N 0.000 claims description 2
- 229960000984 tocofersolan Drugs 0.000 claims description 2
- 239000002076 α-tocopherol Substances 0.000 claims description 2
- 235000004835 α-tocopherol Nutrition 0.000 claims description 2
- 150000003772 α-tocopherols Chemical class 0.000 claims description 2
- 239000011888 foil Substances 0.000 claims 3
- 239000010408 film Substances 0.000 description 10
- 239000000178 monomer Substances 0.000 description 9
- 239000003623 enhancer Substances 0.000 description 7
- 239000004820 Pressure-sensitive adhesive Substances 0.000 description 6
- PBOSTUDLECTMNL-UHFFFAOYSA-N lauryl acrylate Chemical compound CCCCCCCCCCCCOC(=O)C=C PBOSTUDLECTMNL-UHFFFAOYSA-N 0.000 description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical class OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 5
- YYPNJNDODFVZLE-UHFFFAOYSA-N 3-methylbut-2-enoic acid Chemical compound CC(C)=CC(O)=O YYPNJNDODFVZLE-UHFFFAOYSA-N 0.000 description 4
- 239000013039 cover film Substances 0.000 description 4
- 229920000058 polyacrylate Polymers 0.000 description 4
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 3
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 3
- 125000005250 alkyl acrylate group Chemical group 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 230000035699 permeability Effects 0.000 description 3
- 239000013464 silicone adhesive Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- SOGAXMICEFXMKE-UHFFFAOYSA-N Butylmethacrylate Chemical compound CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical class O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000036765 blood level Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 239000004205 dimethyl polysiloxane Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 150000002734 metacrylic acid derivatives Chemical class 0.000 description 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000003466 welding Methods 0.000 description 2
- NMGPHUOPSWFUEB-UHFFFAOYSA-N 2-(butylamino)ethyl 2-methylprop-2-enoate Chemical compound CCCCNCCOC(=O)C(C)=C NMGPHUOPSWFUEB-UHFFFAOYSA-N 0.000 description 1
- GSQIVVSEVORPJF-UHFFFAOYSA-N 2-(butylamino)ethyl prop-2-enoate Chemical compound CCCCNCCOC(=O)C=C GSQIVVSEVORPJF-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
- WDQMWEYDKDCEHT-UHFFFAOYSA-N 2-ethylhexyl 2-methylprop-2-enoate Chemical compound CCCCC(CC)COC(=O)C(C)=C WDQMWEYDKDCEHT-UHFFFAOYSA-N 0.000 description 1
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 description 1
- YXYJVFYWCLAXHO-UHFFFAOYSA-N 2-methoxyethyl 2-methylprop-2-enoate Chemical compound COCCOC(=O)C(C)=C YXYJVFYWCLAXHO-UHFFFAOYSA-N 0.000 description 1
- HFCUBKYHMMPGBY-UHFFFAOYSA-N 2-methoxyethyl prop-2-enoate Chemical compound COCCOC(=O)C=C HFCUBKYHMMPGBY-UHFFFAOYSA-N 0.000 description 1
- QZPSOSOOLFHYRR-UHFFFAOYSA-N 3-hydroxypropyl prop-2-enoate Chemical compound OCCCOC(=O)C=C QZPSOSOOLFHYRR-UHFFFAOYSA-N 0.000 description 1
- WHNPOQXWAMXPTA-UHFFFAOYSA-N 3-methylbut-2-enamide Chemical compound CC(C)=CC(N)=O WHNPOQXWAMXPTA-UHFFFAOYSA-N 0.000 description 1
- NQSLZEHVGKWKAY-UHFFFAOYSA-N 6-methylheptyl 2-methylprop-2-enoate Chemical compound CC(C)CCCCCOC(=O)C(C)=C NQSLZEHVGKWKAY-UHFFFAOYSA-N 0.000 description 1
- DXPPIEDUBFUSEZ-UHFFFAOYSA-N 6-methylheptyl prop-2-enoate Chemical compound CC(C)CCCCCOC(=O)C=C DXPPIEDUBFUSEZ-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical group [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 206010052649 Primary hypogonadism Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 206010059594 Secondary hypogonadism Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 239000004840 adhesive resin Substances 0.000 description 1
- 229920006223 adhesive resin Polymers 0.000 description 1
- 206010003883 azoospermia Diseases 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical compound CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 description 1
- FWLDHHJLVGRRHD-UHFFFAOYSA-N decyl prop-2-enoate Chemical compound CCCCCCCCCCOC(=O)C=C FWLDHHJLVGRRHD-UHFFFAOYSA-N 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- LNCPIMCVTKXXOY-UHFFFAOYSA-N hexyl 2-methylprop-2-enoate Chemical compound CCCCCCOC(=O)C(C)=C LNCPIMCVTKXXOY-UHFFFAOYSA-N 0.000 description 1
- LNMQRPPRQDGUDR-UHFFFAOYSA-N hexyl prop-2-enoate Chemical compound CCCCCCOC(=O)C=C LNMQRPPRQDGUDR-UHFFFAOYSA-N 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 238000002657 hormone replacement therapy Methods 0.000 description 1
- 201000003368 hypogonadotropic hypogonadism Diseases 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 208000008634 oligospermia Diseases 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000037368 penetrate the skin Effects 0.000 description 1
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- 229920000098 polyolefin Polymers 0.000 description 1
- 206010036596 premature ejaculation Diseases 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
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- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 229920001897 terpolymer Polymers 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- 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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/26—Androgens
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
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- Health & Medical Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Reproductive Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- General Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Gynecology & Obstetrics (AREA)
- Nanotechnology (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Molecular Biology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Pregnancy & Childbirth (AREA)
- Diabetes (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
Description
Oblasť technikyTechnical field
Predložený vynález sa týka transdermálneho terapeutického systému na podávanie testosterónu alebo jeho derivátov ako účinnej látky.The present invention relates to a transdermal therapeutic system for the administration of testosterone or derivatives thereof as an active ingredient.
Doterajší stav technikyBACKGROUND OF THE INVENTION
Podľa súčasného stavu techniky sa testosterón a deriváty testosterónu používajú konkrétne na hormonálnu náhradnú terapiu mužov. Ďalšími indikáciami, spolu s primárnym a sekundárnym hypogonadizmom, sú oligozoospermia, impotencia a predčasná ejakulácia. V súčasnosti prebiehajú testy na ich použitie v prípade oeteoporózy u mužov; viď napríklad Rapado a kol., in: Trends in Osteoporosis, l (1989) l-9.According to the state of the art, testosterone and testosterone derivatives are used in particular for hormone replacement therapy in men. Other indications, along with primary and secondary hypogonadism, are oligozoospermia, impotence and premature ejaculation. Tests for their use in the case of oeteoporosis in men are currently underway; see, for example, Rapado et al., in: Trends in Osteoporosis, 1 (1989) 1-9.
Vďaka vysokému účinku prvého priechodu je testosterón rozsiahle neúčinný pri orálnom podaní. Preto sa pri náhradnej terapii podávajú buď orálne účinné estery, ako je undekanoát testosterónu, alebo injekčné prípravky s predĺženým účinkom, ako je enantát testosterónu a propionát testosterónu.Due to the high first-pass effect, testosterone is largely ineffective when administered orally. Therefore, either orally active esters such as testosterone undecanoate or sustained-release injectables such as testosterone enanthate and testosterone propionate are administered in replacement therapy.
Tieto dáta poskytujú rad východzích bodov pre zmysluplný vývoj transdermálnych terapeutických systémov (TTS). S použitím týchto systémov sa je možné vyhnúť vysokým dávkam účinnej zložky pri orálnom dávkovaní, obídu sa bolestivé injekcie a hladina v krvi môže byť lepšie regulovaná a lepšie prispôsobená dennému rytmu.This data provides a number of starting points for meaningful development of transdermal therapeutic systems (TTS). Using these systems, high doses of the active ingredient can be avoided with oral dosing, painful injections can be bypassed, and blood levels can be better regulated and better adapted to the daily rhythm.
Napríklad v US-A-4 704 282 sa popisuje transdermálny terapeutický systém, ktorý má nosnú fóliu (zpevňujúci prostriedok), zásobník účinnej zložky a odstránitelnú kryciu fóliu (odlepovacia páska). Zásobník účinnej zložky môže byť vo forme vodného alebo nevodného gélu alebo polymérneho materiálu, v ktorom je účinná zložka rozpustená v koncentrácii, ktorá nie je vyššia, než je nasýtená koncentrácia účinnej zložky v materiáli matrice. Matrice môže obsahovať prostriedky zvyšujúce priestupnosť. Účinnou zložkou, ktorá má byť podávaná, môže byť napríklad testosterón. Samozrejme ak je testosterón v transdermálnom terapeutickom systéme prítomný v menej než nasýtenom roztoku, je na získanie vyhovujúcich hladín v krvi prítomnosť prostriedkov zvyšujúcich priepustnosť nevyhnutná, viď WO-A-9 210 231, str. 11, riadok 33.For example, US-A-4 704 282 discloses a transdermal therapeutic system having a carrier film (a strengthening agent), an active ingredient reservoir, and a removable cover film (a release tape). The reservoir of the active ingredient may be in the form of an aqueous or non-aqueous gel or polymeric material in which the active ingredient is dissolved in a concentration not higher than the saturated concentration of the active ingredient in the matrix material. The matrix may include permeation enhancers. For example, the active ingredient to be administered may be testosterone. Of course, if testosterone is present in a transdermal therapeutic system in a less than saturated solution, the presence of permeation enhancers is necessary to obtain satisfactory blood levels, see WO-A-9 210 231, p. 11, line 33.
V US-A-4 849 224 sa navrhuje transdermálny terapeutický systém, v ktorom je zásobník účinnej zložky tvorený nosnou fóliou (podkladová fólia) a poréznou membránou. Účinnou zložkou môže byť testosterón alebo ester testosterónu. Okrem účinnej zložky môžu byť prítomné prostriedky zvyšujúce priestupnosť. Na použitelnosť tohto známeho systému je však potrebné pozerať kriticky, pretože zásobník účinnej zložky, ktorý je tvorený laminátom z nosnej fólie a membrány, sa lepí na kožu krúžkom lepidla. Pretože je lepidlo nanesené vo forme prstenca, je v skutočnosti vytvorené okno, cez ktoré môže účinná zložka a prostriedok zvyšujúci priestupnosť prenikať do kože cez membránu bez toho, že by sa prostriedok zvyšujúci priestupnosť dostal nevyhnutne do styku s lepidlom, pričom na ochranu lepidla sú vytvorené prídavné prstencové tesniace prvky. Pretože môže byť s prstencovou lepivou zónou získaná len obmedzená lepivosť, je veľkosť tejto známej náplaste obmedzená.US-A-4,849,224 proposes a transdermal therapeutic system in which the reservoir of the active ingredient is formed by a carrier film (backing film) and a porous membrane. The active ingredient may be testosterone or a testosterone ester. In addition to the active ingredient, permeation enhancers may be present. However, the applicability of this known system must be viewed critically, since the reservoir of the active ingredient, which is a laminate of a carrier film and a membrane, is adhered to the skin by an adhesive ring. Because the adhesive is applied in the form of a ring, in fact a window is formed through which the active ingredient and the permeation enhancer can penetrate the skin through the membrane without the permeability enhancement necessarily coming into contact with the adhesive, while protecting the adhesive are provided additional annular sealing elements. Since only a limited tack can be obtained with the annular adhesive zone, the size of this known patch is limited.
WO-A-9 210 231 = EP-A-0 562 041 je založený na stave techniky z US-A-4 849 224, podľa ktorého je vytvorený prstenec lepidla pre adhéziu transdermálneho terapeutického systému ku koži; viď WO-A-9 210 231, str. 13, riadky 18/19. Alternatívne je navrhnutá základná vrstva lepidla pod zásobníkom (zvláštna základná vrstva lepidla ležiaca pod zásobníkom) a k tomu adhézny povlak pre zásobník (adhézne prekrytie zásobníka). Pretože je však podľa tohto známeho stavu techniky na podávanie testosterónu nevyhnutné použitie prostriedkov zvyšujúcich priestupnosť, nie je jasné, ako chce WO-A-9 210 231 zabrániť nežiaducemu preniknutiu prostriedku zvyšujúceho priestupnosť do lepidla, pokiaľ nie je lepidlo vytvorené v prstencovitej forme.WO-A-9 210 231 = EP-A-0 562 041 is based on the prior art of US-A-4,849,224, according to which an adhesive ring is formed for adhesion of the transdermal therapeutic system to the skin; see WO-A-9 210 231, p. 13, lines 18/19. Alternatively, an adhesive base layer is provided underneath the container (a separate adhesive base layer lying underneath the container) and an adhesive coating for the container (adhesive overlap of the container). However, since the use of permeation enhancers is necessary in the prior art for the administration of testosterone, it is not clear how WO-A-9 210 231 intends to prevent unwanted penetration of the permeation enhancers into the adhesive unless the adhesive is formed in an annular form.
WO-A 9 503 764, WO-A-9 423 707 a US-A-5 152 997 tiež popisujú transdermálne terapeutické systémy na podávanie testosterónu, pričom tieto systémy sú systémy so zásobníkmi, v ktorých je účinná zložka prítomná v nižšej než nasýtenej forme, a sú vybavené urýchľovačom priestupnosti. Tieto popisy známeho stavu tak korešpondujú so stavom techniky, ako je uvedené v WO-A-9 210 231, str. 11, riadok 33.WO-A 9 503 764, WO-A-9 423 707 and US-A-5 152 997 also disclose transdermal therapeutic systems for the administration of testosterone, which systems are reservoir systems in which the active ingredient is present in a lower than saturated form , and are equipped with a permeability accelerator. These prior art descriptions thus correspond to the prior art as disclosed in WO-A-9 210 231, p. 11, line 33.
Úlohou vynálezu je poskytnúť transdermálny terapeutický systém na podávanie testosterónu alebo derivátov testosterónu, ktorý nevyžaduje použitie prostriedkov zvyšujúcich priestupnosť a ktorý zaručuje dostatočnú hladinu účinnej zložky v krvi.SUMMARY OF THE INVENTION It is an object of the present invention to provide a transdermal therapeutic system for the administration of testosterone or testosterone derivatives which does not require the use of permeation enhancers and which provides a sufficient level of the active ingredient in the blood.
Podstata vynálezuSUMMARY OF THE INVENTION
Na tento účel je navrhnutý podľa predloženého vynálezu transdermálny terapeutický systém (TTS) na podávanie testosterónu alebo derivátov testosterónu ako účinnej zložky, ktorý máFor this purpose, a transdermal therapeutic system (TTS) for administering testosterone or testosterone derivatives as an active ingredient having a
- nosnú fóliu (podkladovú fóliu),- carrier film (backing film),
- zásobník,- container,
- alkoholový nosič účinnej zložky,- alcohol carrier of the active ingredient,
- adhéznu vrstvu pre styk systému s kožou, aan adhesive layer for contacting the system with the skin, and
- odstrániteľnú kryciu fóliu (odlepovaciu pásku), v ktorom- a removable cover film (release tape) in which
- systém neobsahuje prostriedok zvyšujúci priestupnosť,- the system does not contain a permeability enhancer,
- účinná zložka je v nosiči účinnej zložky prítomná v nasýtení athe active ingredient is present in the carrier of the active ingredient in saturation, and
- medzi zásobníkom a adhéznou vrstvou je vytvorená membrána,- a membrane is formed between the container and the adhesive layer,
- ktorá neriadi uvoľňovanie účinnej zložky, zatiaľ čo uvoľňovanie účinnej zložky riadi adhézna vrstva.- which does not control the release of the active ingredient, while the release of the active ingredient controls the adhesive layer.
Vynález je založený na prekvapivom zistení, že dostatočné množstvo účinnej zložky v krvi môže byť dosiahnuté tiež či predovšetkým vtedy, keď je účinná zložka prítomná v nosiči pre účinnú látku v nasýtení, zatiaľ čo WO-A-9 210 231 vyžaduje nižšiu koncentráciu než nasýtenie účinnej zložky.The invention is based on the surprising finding that a sufficient amount of the active ingredient in the blood can also be achieved, especially if the active ingredient is present in the carrier for the active ingredient in saturation, whereas WO-A-9 210 231 requires a lower concentration than the active ingredient saturation. components.
Podľa vynálezu je možné použiť ako deriváty testosterónu ester testosterónu, predovšetkým enantát testosterónu, cipionát testosterónu, propionát testosterónu alebo undekanoát testosterónu, alebo nižšie alkyltestosteróny, predovšetkým metyltestosterón.According to the invention, testosterone esters, in particular testosterone enanthate, testosterone cipionate, testosterone propionate or testosterone undecanoate, or lower alkylltestosterones, in particular methyltestosterone, can be used as testosterone derivatives.
t e t e
Účinná zložka môže byť prítomná vo forme komplexu s cyklodextrínom alebo derivátmi cyklodextrínu, predovšetkým s β-cyklodextrínom.The active ingredient may be present in the form of a complex with cyclodextrin or cyclodextrin derivatives, in particular β-cyclodextrin.
Membránou môže byť membrána z polyetylénu alebo membrána z polypropylénu.The membrane may be a polyethylene membrane or a polypropylene membrane.
Podľa výhodného uskutočnenia je zásobník tvorený nosnou fóliou a membránou.According to a preferred embodiment, the container is formed by a carrier film and a membrane.
Podľa vynálezu môže byť alkoholovým nosičom účinnej látky etanol alebo nízkomolekulámy monohydroxyalkohol, ako je izopropanol, alebo nízkomolekulámy polyhydroxyalkohol, napríklad propylénglykol, alebo ich zmes.According to the invention, the alcoholic active ingredient can be ethanol or low molecular weight monohydroxy alcohol, such as isopropanol, or low molecular weight polyhydroxy alcohol, for example propylene glycol, or a mixture thereof.
Pre adhéznu vrstvu podľa vynálezu môže byť vybrané lepidlo citlivé na tlak (samolepiace lepidlo), odolné voči alkoholu, na báze napríklad polyuretánu, izobutylénu, polyvinyléteru, silikónu alebo akrylátu.An alcohol-resistant pressure-sensitive adhesive (pressure-sensitive adhesive) may be selected for the adhesive layer according to the invention, based, for example, on polyurethane, isobutylene, polyvinyl ether, silicone or acrylate.
Lepidlom na báze silikónu môže byť silikónové lepidlo, ktoré je založené na dvoch hlavných zložkách; polymére alebo lepidle, predovšetkým polysiloxáne, a lepiacej živici. Polysiloxánové lepidlo je obvykle tvorené zosieťovadlom lepidla, typicky vysokomolekulárnym polydiorganosiloxánom, a živicou, aby sa použitím vhodného organického rozpúšťadla získala trojrozmerná kremičitanová štruktúra. Zmes živice s polymérom je najdôležitejším faktorom pre zmenu fyzikálnych vlastností polysiloxánových lepidiel; viď napríklad Sobieski a»kol., Sili-cone Pressure Sensitive Adhesives, Handbook of Pressure Sensitive Adhesive Technology, 2. vyd., str. 508-517 (ed. D. Satas), Van Nostrand Reinhold, New York (1989).The silicone-based adhesive may be a silicone adhesive which is based on two main components; polymers or adhesives, in particular polysiloxane, and an adhesive resin. The polysiloxane adhesive is typically comprised of an adhesive crosslinker, typically a high molecular weight polydiorganosiloxane, and a resin, to obtain a three-dimensional silicate structure using a suitable organic solvent. The resin / polymer mixture is the most important factor for altering the physical properties of polysiloxane adhesives; see, for example, Sobieski et al., Silicon Pressure Sensitive Adhesives, Handbook of Pressure Sensitive Adhesive Technology, 2nd Ed., p. 508-517 (eds. D. Satas), Van Nostrand Reinhold, New York (1989).
Vhodné samolepiace silikónové lepidlá je možné bežne získať pod ochrannou známkou BIO-PSA X7.Suitable self-adhesive silicone adhesives are commonly available under the trademark BIO-PSA X7.
Ďalším príkladom lepidel citlivých na tlak na báze silikónov je trimetylovaný silikóndioxid, ktorý bol spracovaný s polydimetylsiloxánom s koncovými trimetylsiloxyskupinami.Another example of silicone based pressure sensitive adhesives is trimethylated silicone dioxide which has been treated with polydimethylsiloxane having trimethylsiloxy terminal groups.
Lepidlom na báze akrylátov môže byť akýkoľvek homopolymér, kopolymér alebo terpolymér, pozostávajúci z rôznych derivátov kyseliny akrylovej.The acrylate-based adhesive may be any homopolymer, copolymer or terpolymer, consisting of various derivatives of acrylic acid.
Napríklad môžu byť akrylátovými polymérmi polyméry jedného alebo viac monomérov kyseliny akrylovej a iných kopolymérovateľných monomérov. Akrylátové polyméry tiež môžu obsahovať kopolyméry alkylakrylátov a/alebo metakrylátov a/alebo kopolymérovateľných sekundárnych monomérov alebo monomérov s funkčnými skupinami. Kohézne vlastnosti získaných akrylátových polymérov je možné meniť zmenami množstva každého typu, ktorý sa pridá ako monomér. Všeobecne pozostáva akrylátový polymér z najmenej 50 % hmotn.For example, the acrylate polymers may be polymers of one or more acrylic acid monomers and other copolymerizable monomers. The acrylate polymers may also contain copolymers of alkyl acrylates and / or methacrylates and / or copolymerizable secondary or functionalized monomers. The cohesive properties of the obtained acrylate polymers can be varied by varying the amount of each type that is added as a monomer. Generally, the acrylate polymer consists of at least 50 wt.
akrylátového, metakrylátového, alkylakrylátového alebo alkylmetakrylátového monoméru, od 0 do 20 % funkčného monoméru, kopolymérovateľného s akrylátom, a od 0 do 40 % odlišného monoméru.an acrylate, methacrylate, alkyl acrylate or alkyl methacrylate monomer, from 0 to 20% of a functional monomer copolymerizable with acrylate, and from 0 to 40% of a different monomer.
Akrylátovými monomérmi, ktoré môžu byť použité s kyselinou akrylovou, sú kyselina metakrylová, butylakrylát, butylmetakrylát, hexylakrylát, hexylmetakrylát, izooktylakrylát, izooktylmetakrylát, 2-etylhexylakrylát, 2-etylhexylmetakrylát, decylakrylát, decylmetakrylát, dodecylakrylát, dodecylmetakrylát, tridecylakrylát a tridecylmetakrylát.Acrylate monomers which may be used with acrylic acid are methacrylic acid, butyl acrylate, butyl methacrylate, hexyl acrylate, hexyl methacrylate, isooctyl acrylate, isooctyl methacrylate, 2-ethylhexylacrylate, 2-ethylhexyl methacrylate, decyl acrylate, dodecyl acrylate, dodecyl acrylate, dodecyl acrylate, dodecyl acrylate, dodecyl acrylate, dodecyl acrylate.
Ako funkčné monoméry, ktoré sú kopolymérovateľné s vyššie uvedenými akrylátmi, metakrylátmi, alkylakrylátmi alebo alkylmetakrylátmi môžu byť napríklad použité kyselina akrylová, kyselina metakrylová, kyselina maleinová, maleinanhydrid, hydroxyetylakrylát, hydroxypropylakrylát, akrylamid, dimetylakrylamid, akrylonitril, dimetylaminoetylakrylát, dimetylaminoetylmetakrylát, terc. butylaminoetylakrylát, terc. butylamino-etylmetakrylát, metoxyetylakrylát a metoxyetylmetakrylát.As functional monomers which are copolymerizable with the aforementioned acrylates, methacrylates, alkyl acrylates or alkyl methacrylates, for example, acrylic acid, methacrylic acid, maleic acid, maleic anhydride, hydroxyethyl acrylate, hydroxypropyl acrylate, acrylamide, dimethylacrylamide, dimethylacrylate, dimethylacrylate, dimethylacrylate, dimethylacrylate. butylaminoethyl acrylate, tert. butylaminoethyl methacrylate, methoxyethyl acrylate and methoxyethyl methacrylate.
Ďalšie podrobnosti a príklady samolepiacich akrylátov, vhodných pre vynález, sú opísané v Satas Handbook of Pressure Sensitive Adhesive Technology Acrylic Adhesivés, 2. vyd., str. 396-456 (ed. D. Satas), Van Nostrand Reinhold, New York (1989).Further details and examples of self-adhesive acrylates suitable for the invention are described in the Satas Handbook of Pressure Sensitive Adhesive Technology Acrylic Adhesives, 2nd Ed., P. 396-456 (ed. D. Satas), Van Nostrand Reinhold, New York (1989).
Vhodné samolepiace akryláty sú komerčne dostupné.Suitable self-adhesive acrylates are commercially available.
Transdermálny terapeutický systém podľa vynálezu môže prídavné obsahovať a-tokoferol alebo deriváty α-tokoferolu a/alebo činidlo zvyšujúce viskozitu, ako je hydroxypropylcelulóza.The transdermal therapeutic system of the invention may additionally comprise α-tocopherol or α-tocopherol derivatives and / or a viscosity enhancing agent such as hydroxypropylcellulose.
Vynález bude ďalej podrobnejšie znázornený obrázkom a príkladom.The invention will now be illustrated in more detail by way of illustration and example.
Prehľad obrázkov na výkreseOverview of the figures in the drawing
Podľa obrázku 1 obsahuje transdermálny terapeutický systém podľa vynálezu nosnú fóliu (podkladová fólia) i, ktorá môže mať nepatrne konvexný tvar, a ktorá spoločne s membránou 3 tvorí zásobník 2, pričom membrána 3 nereguluje uvoľňovanie účinnej zložky. Na membránu 3 je nanesená podľa obrázku 1 adhézna vrstva 5, ktorá reguluje uvoľňovanie účinnej látky. Adhézna vrstva 5 je ďalej prekrytá krycou fóliou (odlepovacia páska) 6, ktorá sa pred aplikáciou odstráni.According to Figure 1, the transdermal therapeutic system according to the invention comprises a carrier film (backing film) 1 which may have a slightly convex shape and which together with the membrane 3 forms a reservoir 2, the membrane 3 not regulating the release of the active ingredient. The membrane 3 is coated according to FIG. 1 with an adhesive layer 5 which regulates the release of the active substance. The adhesive layer 5 is further covered with a cover film (peel-off tape) 6 which is removed prior to application.
Podľa obrázku 1 môže byť nosná fólia 1 vybavená prstencovým olemovaním 4, ktoré leží na obvodovej okrajovej oblasti adhéznej vrstvy 5 a je nalepené v mieste dotyku na membránu 3.According to Figure 1, the carrier film 1 can be provided with an annular bead 4 which lies on the peripheral edge area of the adhesive layer 5 and is glued at the point of contact with the membrane 3.
Príklad uskutočneniaExample
Ako adhézna vrstva sa použije samolepiace lepidlo na báze silikónu (trimetylovaný silikón-dioxid, ktorý bol spracovaný s polydimetylsiloxánom majúcim koncové trimetylsiloxyskupiny; hrúbka vrstvy za sucha je približne od 35 do 45 gm; hmotnosť na jednotku špecifického povrchu je približne od 50 do 60 g/m^). Krycia fólia z PET (hrúbka približne 75 gm, hmotnosť na jednotku špecifického povrchu je približne 100 g/m^) je pokrytá pomocou poťahovacieho zariadenia silikónovým lepidlom. Mikroporézna polyetylénová membrána alebo mikroporézna polypropylénová membrána (teplom zvarovateľná; hrúbka približne 50 gm; hmotnosť na jednotku špecifického povrchu je približne 10 g/m^) sa potom laminuje na potiahnutú kryciu fóliu za vzniku laminátu z krycej fólie, lepidla a membrány. Laminát sa potom privarí na nosnú fóliu z polyesteru (aluminizovaná s polyolefinovou lepiacou vrstvou (teplom zvarovateľná); hrúbka približne 70 gm) pomocou zvarovacieho zariadenia (so zvarovacím prstencom) takým spôsobom, že na zavedenie účinnej látky zostane medzera. Plniteľný transdermálny terapeutický systém (prázdny TTS) sa naplní, napríklad použitím Hamiltonovej injekčnej striekačky alebo rúrkového čerpadla vybaveného kanylou, nasledujúcim roztokom účinnej zložky:The adhesive layer is a silicone-based adhesive (trimethylated silicone dioxide which has been treated with polydimethylsiloxane having trimethylsiloxy groups; the dry layer thickness is from about 35 to 45 gm; the weight per unit specific surface area is from about 50 to 60 g / m ^). A PET cover film (thickness of about 75 gm, weight per unit specific surface area of about 100 g / m 2) is covered with a silicone adhesive coating device. The microporous polyethylene membrane or microporous polypropylene membrane (heat sealable; thickness of about 50 gm; weight per unit specific surface area is about 10 g / m 2) is then laminated to the coated liner to form a liner of liner, adhesive and membrane. The laminate is then welded onto a polyester backing sheet (aluminized with a polyolefin adhesive layer (heat-sealable); thickness of about 70 gm) using a welding device (with a welding ring) in such a way that a gap remains to introduce the active agent. The refillable transdermal therapeutic system (empty TTS) is filled, for example, using a Hamilton syringe or cannula tube pump, with the following active ingredient solution:
Zloženie roztoku účinnej zložky pre TTS:Composition of the active ingredient solution for TTS:
Po naplnení sa medzera na plnenie zavarí. Naplnené transdermálne terapeutické systémy sa vyrážajú pomocou tŕňa.After filling, the filling gap is sealed. Filled transdermal therapeutic systems are punched with a thorn.
Claims (8)
Applications Claiming Priority (2)
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|---|---|---|---|
| DE19517145A DE19517145C2 (en) | 1995-05-10 | 1995-05-10 | Transdermal therapeutic system (TTS) for administration of testosterone |
| PCT/EP1996/002013 WO1996035427A1 (en) | 1995-05-10 | 1996-05-10 | Transdermal therapeutic system for administering testosterone |
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| SK149797A3 true SK149797A3 (en) | 1998-05-06 |
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| SK1497-97A SK149797A3 (en) | 1995-05-10 | 1996-05-10 | Transdermal therapeutic system (tts) for administering testosterone |
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| EP (1) | EP0825865B1 (en) |
| JP (1) | JPH11504643A (en) |
| CN (1) | CN1183723A (en) |
| AT (1) | ATE208200T1 (en) |
| AU (1) | AU702710B2 (en) |
| BR (1) | BR9608255A (en) |
| CA (1) | CA2220358A1 (en) |
| CZ (1) | CZ287678B6 (en) |
| DE (2) | DE19517145C2 (en) |
| DK (1) | DK0825865T3 (en) |
| HU (1) | HUP9801130A3 (en) |
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| NZ (1) | NZ308516A (en) |
| PL (1) | PL323145A1 (en) |
| SK (1) | SK149797A3 (en) |
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| AU1429697A (en) * | 1995-12-29 | 1997-07-28 | Cygnus, Inc. | Systems and methods for the transdermal administration of androgenic agents |
| DE69716737T2 (en) * | 1996-07-03 | 2003-03-20 | Alza Corp., Palo Alto | DEVICES FOR DRUG DELIVERY AND MANUFACTURING METHOD |
| US6007837A (en) * | 1996-07-03 | 1999-12-28 | Alza Corporation | Drug delivery devices and process of manufacture |
| DE19646050A1 (en) * | 1996-11-08 | 1998-05-14 | Labtec Gmbh | Transdermal therapeutic system e.g. containing testosterone, melatonin |
| US6174545B1 (en) | 1997-07-01 | 2001-01-16 | Alza Corporation | Drug delivery devices and process of manufacture |
| ES2226394T3 (en) * | 1998-05-22 | 2005-03-16 | Novosis Ag | TRANSDERMAL SYSTEMS CONTAINING ACTIVE SUBSTANCE THAT IS RELEASED CONTROLLED IN TIME. |
| FR2793689B1 (en) * | 1999-05-19 | 2001-08-24 | Pf Medicament | TRANSDERMAL DEVICE FOR THE ADMINISTRATION OF TESTOSTERONE OR A DERIVATIVE THEREOF |
| US6503894B1 (en) | 2000-08-30 | 2003-01-07 | Unimed Pharmaceuticals, Inc. | Pharmaceutical composition and method for treating hypogonadism |
| US8173155B2 (en) | 2004-06-01 | 2012-05-08 | Hisamitsu Pharmaceutical Co., Inc. | Adhesive patch |
| PT1937276E (en) | 2005-10-12 | 2013-02-21 | Besins Healthcare Luxembourg | Improved testosterone gel and method of use |
| FR2895679B1 (en) * | 2005-12-29 | 2012-06-08 | Pf Medicament | STABILIZATION OF TESTOSTERONE IN TRANSDERMAL DEVICES |
| CN101480399B (en) * | 2008-09-25 | 2011-10-05 | 宋博 | Application of andrusol in preparing medicament for treating asthenospermia |
| DE102011012712A1 (en) | 2011-03-01 | 2012-09-06 | Frank Lehmann-Horn | Use of aldosterone receptor antagonists for the treatment of female sexual dysfunction |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4286592A (en) * | 1980-02-04 | 1981-09-01 | Alza Corporation | Therapeutic system for administering drugs to the skin |
| US4725439A (en) * | 1984-06-29 | 1988-02-16 | Alza Corporation | Transdermal drug delivery device |
| US4704282A (en) * | 1984-06-29 | 1987-11-03 | Alza Corporation | Transdermal therapeutic system having improved delivery characteristics |
| US4849224A (en) * | 1987-11-12 | 1989-07-18 | Theratech Inc. | Device for administering an active agent to the skin or mucosa |
| GB8804164D0 (en) * | 1988-02-23 | 1988-03-23 | Tucker J M | Bandage for administering physiologically active compound |
| US5474783A (en) * | 1988-03-04 | 1995-12-12 | Noven Pharmaceuticals, Inc. | Solubility parameter based drug delivery system and method for altering drug saturation concentration |
| US5152997A (en) * | 1990-12-11 | 1992-10-06 | Theratech, Inc. | Method and device for transdermally administering testosterone across nonscrotal skin at therapeutically effective levels |
| MX9202350A (en) * | 1991-05-20 | 1992-11-01 | Alza Corp | SKIN PENETRATION INCREMENTING COMPOSITIONS USING GLYCEROL MONOLINOLEATE. |
| CA2075517C (en) * | 1992-04-01 | 1997-03-11 | John Wick | Transdermal patch incorporating a polymer film incorporated with an active agent |
| ATE184473T1 (en) * | 1992-06-11 | 1999-10-15 | Theratech Inc | USE OF GLYCERINE TO ATTENUATE TRANSDERMAL DRUG ADMINISTRATION |
| EP0695177B1 (en) * | 1993-04-20 | 1998-02-18 | Hexal Ag | Active substance-containing plaster |
| DE4313402A1 (en) * | 1993-04-23 | 1994-10-27 | Hexal Pharma Gmbh | Transdermal preparation of active compound |
| US5460820B1 (en) * | 1993-08-03 | 1999-08-03 | Theratech Inc | Method for providing testosterone and optionally estrogen replacement therapy to women |
-
1995
- 1995-05-10 DE DE19517145A patent/DE19517145C2/en not_active Expired - Fee Related
-
1996
- 1996-05-10 CZ CZ19973512A patent/CZ287678B6/en not_active IP Right Cessation
- 1996-05-10 AU AU58050/96A patent/AU702710B2/en not_active Ceased
- 1996-05-10 DK DK96919765T patent/DK0825865T3/en active
- 1996-05-10 PL PL96323145A patent/PL323145A1/en unknown
- 1996-05-10 NZ NZ308516A patent/NZ308516A/en unknown
- 1996-05-10 SK SK1497-97A patent/SK149797A3/en unknown
- 1996-05-10 CA CA002220358A patent/CA2220358A1/en not_active Abandoned
- 1996-05-10 WO PCT/EP1996/002013 patent/WO1996035427A1/en active IP Right Grant
- 1996-05-10 BR BR9608255A patent/BR9608255A/en not_active Application Discontinuation
- 1996-05-10 HU HU9801130A patent/HUP9801130A3/en unknown
- 1996-05-10 CN CN96193748A patent/CN1183723A/en active Pending
- 1996-05-10 DE DE59608150T patent/DE59608150D1/en not_active Expired - Fee Related
- 1996-05-10 AT AT96919765T patent/ATE208200T1/en not_active IP Right Cessation
- 1996-05-10 EP EP96919765A patent/EP0825865B1/en not_active Expired - Lifetime
- 1996-05-10 ZA ZA963743A patent/ZA963743B/en unknown
- 1996-05-10 JP JP8533786A patent/JPH11504643A/en active Pending
-
1997
- 1997-11-07 NO NO975140A patent/NO975140L/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0825865B1 (en) | 2001-11-07 |
| HUP9801130A2 (en) | 1998-08-28 |
| CZ287678B6 (en) | 2001-01-17 |
| BR9608255A (en) | 1999-02-02 |
| ATE208200T1 (en) | 2001-11-15 |
| NO975140L (en) | 1997-11-10 |
| CA2220358A1 (en) | 1996-11-14 |
| NO975140D0 (en) | 1997-11-07 |
| HUP9801130A3 (en) | 2001-03-28 |
| DE19517145C2 (en) | 2000-02-24 |
| EP0825865A1 (en) | 1998-03-04 |
| ZA963743B (en) | 1996-11-18 |
| NZ308516A (en) | 1999-05-28 |
| AU5805096A (en) | 1996-11-29 |
| DE19517145C1 (en) | 1996-11-28 |
| DK0825865T3 (en) | 2002-02-18 |
| CZ351297A3 (en) | 1998-03-18 |
| WO1996035427A1 (en) | 1996-11-14 |
| AU702710B2 (en) | 1999-03-04 |
| JPH11504643A (en) | 1999-04-27 |
| CN1183723A (en) | 1998-06-03 |
| PL323145A1 (en) | 1998-03-16 |
| DE59608150D1 (en) | 2001-12-13 |
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