CA2605112C - Solid transdermal therapeutic system comprising uv absorber - Google Patents
Solid transdermal therapeutic system comprising uv absorber Download PDFInfo
- Publication number
- CA2605112C CA2605112C CA2605112A CA2605112A CA2605112C CA 2605112 C CA2605112 C CA 2605112C CA 2605112 A CA2605112 A CA 2605112A CA 2605112 A CA2605112 A CA 2605112A CA 2605112 C CA2605112 C CA 2605112C
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- CA
- Canada
- Prior art keywords
- transdermal therapeutic
- therapeutic system
- solid transdermal
- absorber
- solid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 230000001225 therapeutic effect Effects 0.000 title claims abstract description 56
- 239000007787 solid Substances 0.000 title claims abstract description 46
- 239000006096 absorbing agent Substances 0.000 title claims abstract description 34
- 239000010410 layer Substances 0.000 claims abstract description 57
- 239000004480 active ingredient Substances 0.000 claims abstract description 48
- 239000011159 matrix material Substances 0.000 claims abstract description 31
- 239000012790 adhesive layer Substances 0.000 claims abstract description 29
- 239000008186 active pharmaceutical agent Substances 0.000 claims abstract description 15
- 230000001681 protective effect Effects 0.000 claims abstract description 9
- -1 hydroxy-phenyltriazine compound Chemical class 0.000 claims description 16
- 239000000583 progesterone congener Substances 0.000 claims description 15
- 239000000853 adhesive Substances 0.000 claims description 12
- 229920000642 polymer Polymers 0.000 claims description 12
- 229920002367 Polyisobutene Polymers 0.000 claims description 7
- 230000035558 fertility Effects 0.000 claims description 5
- 229920000058 polyacrylate Polymers 0.000 claims description 5
- 229920000139 polyethylene terephthalate Polymers 0.000 claims description 5
- 239000005020 polyethylene terephthalate Substances 0.000 claims description 5
- 239000004698 Polyethylene Substances 0.000 claims description 4
- 229940011871 estrogen Drugs 0.000 claims description 4
- 239000000262 estrogen Substances 0.000 claims description 4
- 229920000573 polyethylene Polymers 0.000 claims description 4
- 230000004888 barrier function Effects 0.000 claims description 3
- SIGSPDASOTUPFS-XUDSTZEESA-N gestodene Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@](C=C4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 SIGSPDASOTUPFS-XUDSTZEESA-N 0.000 claims description 3
- 229960005352 gestodene Drugs 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- ROGIWVXWXZRRMZ-UHFFFAOYSA-N 2-methylbuta-1,3-diene;styrene Chemical compound CC(=C)C=C.C=CC1=CC=CC=C1 ROGIWVXWXZRRMZ-UHFFFAOYSA-N 0.000 claims description 2
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 claims description 2
- 239000004743 Polypropylene Substances 0.000 claims description 2
- 229920001328 Polyvinylidene chloride Polymers 0.000 claims description 2
- 239000002131 composite material Substances 0.000 claims description 2
- 229920001577 copolymer Polymers 0.000 claims description 2
- 239000004205 dimethyl polysiloxane Substances 0.000 claims description 2
- 229960002568 ethinylestradiol Drugs 0.000 claims description 2
- 239000005038 ethylene vinyl acetate Substances 0.000 claims description 2
- 239000005556 hormone Substances 0.000 claims description 2
- 229940088597 hormone Drugs 0.000 claims description 2
- 239000012528 membrane Substances 0.000 claims description 2
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 claims description 2
- 229920002239 polyacrylonitrile Polymers 0.000 claims description 2
- 229920001083 polybutene Polymers 0.000 claims description 2
- 229920001195 polyisoprene Polymers 0.000 claims description 2
- 229920001155 polypropylene Polymers 0.000 claims description 2
- 229920002635 polyurethane Polymers 0.000 claims description 2
- 239000004814 polyurethane Substances 0.000 claims description 2
- 229920000915 polyvinyl chloride Polymers 0.000 claims description 2
- 239000004800 polyvinyl chloride Substances 0.000 claims description 2
- 239000005033 polyvinylidene chloride Substances 0.000 claims description 2
- WWYNJERNGUHSAO-XUDSTZEESA-N (+)-Norgestrel Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 WWYNJERNGUHSAO-XUDSTZEESA-N 0.000 claims 1
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 claims 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims 1
- 229960004044 gestodene and ethinylestradiol Drugs 0.000 claims 1
- 229960004400 levonorgestrel Drugs 0.000 claims 1
- VMRIVYANZGSGRV-UHFFFAOYSA-N 4-phenyl-2h-triazin-5-one Chemical class OC1=CN=NN=C1C1=CC=CC=C1 VMRIVYANZGSGRV-UHFFFAOYSA-N 0.000 abstract description 9
- 206010040880 Skin irritation Diseases 0.000 abstract description 2
- 230000036556 skin irritation Effects 0.000 abstract description 2
- 231100000475 skin irritation Toxicity 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 description 22
- 238000009472 formulation Methods 0.000 description 17
- 230000001070 adhesive effect Effects 0.000 description 10
- 229940095055 progestogen systemic hormonal contraceptives Drugs 0.000 description 5
- 230000003711 photoprotective effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 3
- 229960004101 bemotrizinol Drugs 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000002985 plastic film Substances 0.000 description 3
- 230000004224 protection Effects 0.000 description 3
- SITYOOWCYAYOKL-UHFFFAOYSA-N 2-[4,6-bis(2,4-dimethylphenyl)-1,3,5-triazin-2-yl]-5-(3-dodecoxy-2-hydroxypropoxy)phenol Chemical compound OC1=CC(OCC(O)COCCCCCCCCCCCC)=CC=C1C1=NC(C=2C(=CC(C)=CC=2)C)=NC(C=2C(=CC(C)=CC=2)C)=N1 SITYOOWCYAYOKL-UHFFFAOYSA-N 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- XVAMCHGMPYWHNL-UHFFFAOYSA-N bemotrizinol Chemical compound OC1=CC(OCC(CC)CCCC)=CC=C1C1=NC(C=2C=CC(OC)=CC=2)=NC(C=2C(=CC(OCC(CC)CCCC)=CC=2)O)=N1 XVAMCHGMPYWHNL-UHFFFAOYSA-N 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229920006255 plastic film Polymers 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- OIQXFRANQVWXJF-ACCUITESSA-N (2e)-2-benzylidene-4,7,7-trimethylbicyclo[2.2.1]heptan-3-one Chemical compound CC1(C)C2CCC1(C)C(=O)\C2=C\C1=CC=CC=C1 OIQXFRANQVWXJF-ACCUITESSA-N 0.000 description 1
- PDHSAQOQVUXZGQ-JKSUJKDBSA-N (2r,3s)-2-(3,4-dihydroxyphenyl)-3-methoxy-3,4-dihydro-2h-chromene-5,7-diol Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2OC)=CC=C(O)C(O)=C1 PDHSAQOQVUXZGQ-JKSUJKDBSA-N 0.000 description 1
- AALXZHPCKJILAZ-UHFFFAOYSA-N (4-propan-2-ylphenyl)methyl 2-hydroxybenzoate Chemical compound C1=CC(C(C)C)=CC=C1COC(=O)C1=CC=CC=C1O AALXZHPCKJILAZ-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical class C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
- TYYHDKOVFSVWON-UHFFFAOYSA-N 2-butyl-2-methoxy-1,3-diphenylpropane-1,3-dione Chemical compound C=1C=CC=CC=1C(=O)C(OC)(CCCC)C(=O)C1=CC=CC=C1 TYYHDKOVFSVWON-UHFFFAOYSA-N 0.000 description 1
- VSXIZXFGQGKZQG-UHFFFAOYSA-N 2-cyano-3,3-diphenylprop-2-enoic acid Chemical compound C=1C=CC=CC=1C(=C(C#N)C(=O)O)C1=CC=CC=C1 VSXIZXFGQGKZQG-UHFFFAOYSA-N 0.000 description 1
- WSSJONWNBBTCMG-UHFFFAOYSA-N 2-hydroxybenzoic acid (3,3,5-trimethylcyclohexyl) ester Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C1=CC=CC=C1O WSSJONWNBBTCMG-UHFFFAOYSA-N 0.000 description 1
- RJCHCFQTUKAYAA-UHFFFAOYSA-N 5-[[2-amino-5-[(4-methoxyphenyl)methyl]-3-methylimidazol-4-yl]methyl]-2-methoxybenzene-1,3-diol Chemical compound C1=CC(OC)=CC=C1CC1=C(CC=2C=C(O)C(OC)=C(O)C=2)N(C)C(=N)N1 RJCHCFQTUKAYAA-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- YBGZDTIWKVFICR-JLHYYAGUSA-N Octyl 4-methoxycinnamic acid Chemical compound CCCCC(CC)COC(=O)\C=C\C1=CC=C(OC)C=C1 YBGZDTIWKVFICR-JLHYYAGUSA-N 0.000 description 1
- WYWZRNAHINYAEF-UHFFFAOYSA-N Padimate O Chemical compound CCCCC(CC)COC(=O)C1=CC=C(N(C)C)C=C1 WYWZRNAHINYAEF-UHFFFAOYSA-N 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229940064734 aminobenzoate Drugs 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 150000005417 aminobenzoic acid derivatives Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229960005193 avobenzone Drugs 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 229940024874 benzophenone Drugs 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 150000008366 benzophenones Chemical class 0.000 description 1
- 150000001565 benzotriazoles Chemical class 0.000 description 1
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- OKBVVJOGVLARMR-QSWIMTSFSA-N cefixime Chemical compound S1C(N)=NC(C(=N\OCC(O)=O)\C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 OKBVVJOGVLARMR-QSWIMTSFSA-N 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 150000001851 cinnamic acid derivatives Chemical class 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229920002457 flexible plastic Polymers 0.000 description 1
- GKQPCPXONLDCMU-CCEZHUSRSA-N lacidipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C1=CC=CC=C1\C=C\C(=O)OC(C)(C)C GKQPCPXONLDCMU-CCEZHUSRSA-N 0.000 description 1
- 229960004340 lacidipine Drugs 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- DXGLGDHPHMLXJC-UHFFFAOYSA-N oxybenzone Chemical compound OC1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1 DXGLGDHPHMLXJC-UHFFFAOYSA-N 0.000 description 1
- 229960001173 oxybenzone Drugs 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 150000003872 salicylic acid derivatives Chemical class 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- CXVGEDCSTKKODG-UHFFFAOYSA-N sulisobenzone Chemical compound C1=C(S(O)(=O)=O)C(OC)=CC(O)=C1C(=O)C1=CC=CC=C1 CXVGEDCSTKKODG-UHFFFAOYSA-N 0.000 description 1
- 229960000368 sulisobenzone Drugs 0.000 description 1
- 229940072226 suprax Drugs 0.000 description 1
- LOIYMIARKYCTBW-OWOJBTEDSA-N trans-urocanic acid Chemical compound OC(=O)\C=C\C1=CNC=N1 LOIYMIARKYCTBW-OWOJBTEDSA-N 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 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
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- 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
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
-
- 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
-
- 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
- A61P15/18—Feminine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Gynecology & Obstetrics (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to a novel solid transdermal therapeutic system with UV absorber which is particularly designed for photosensitive active pharmaceutical ingredients. The UV-stable transdermal therapeutic system (TTS) consists of a backing layer 1, of at least one active ingredient-containing matrix 2 and of a detachable protective film 3, it optionally being for an adhesive layer 4 and a separating layer 5 to be introduced between the backing layer 1 and the active ingredient-containing matrix 2. UV absorbers from the group of hydroxyphenyltriazines can be embedded in the backing layer 1 or in the active ingredient-containing matrix 2 or in the adhesive layer 4.
The TTS according to the invention achieves high stability with a low concentration of UV absorber. It is thus possible in particular to avoid or reduce the risk of possible skin irritation.
The TTS according to the invention achieves high stability with a low concentration of UV absorber. It is thus possible in particular to avoid or reduce the risk of possible skin irritation.
Description
Solid transdermal therapeutic system comprising UV
absorber (Description) Technical Field The invention relates to a solid transdermal therapeutic system with UV absorber. The UV-stable transdermal therapeutic system (TTS) is particularly designed for photosensitive active pharmaceutical ingredients.
The transdermal therapeutic system according to the invention, if appropriate comprising a progestrogen and/or an estrogen, is also suitable for fertility control.
Prior Art Attempts. to employ photosensitive active ingredients which absorb UV-A and UV-B rays normally in sun creams ,are known, as described by Briscart & Plaizier-Vercammen (Proc. 2nd World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, APGI/APV, 1998, 1231-1232).
The patent literature further discloses the protection of transdermal therapeutic systems (TTS) provided with photosensitive active ingredients by means of visually conspicuous aluminized or lacquered covering films as backing layer of the TTS.
WO-Al-00/56289 describes a method for protecting therapeutic preparations, systems or their constituents, the intention being to achieve in each case specific protection from degradation by harmful factors such as atmospheric oxygen, water and/or light.
Photoprotective substances which absorb or reflect electromagnetic waves are used, employing respectively absorbents or reflectants whose absorption or reflection spectrum covers the wavelength range
absorber (Description) Technical Field The invention relates to a solid transdermal therapeutic system with UV absorber. The UV-stable transdermal therapeutic system (TTS) is particularly designed for photosensitive active pharmaceutical ingredients.
The transdermal therapeutic system according to the invention, if appropriate comprising a progestrogen and/or an estrogen, is also suitable for fertility control.
Prior Art Attempts. to employ photosensitive active ingredients which absorb UV-A and UV-B rays normally in sun creams ,are known, as described by Briscart & Plaizier-Vercammen (Proc. 2nd World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, APGI/APV, 1998, 1231-1232).
The patent literature further discloses the protection of transdermal therapeutic systems (TTS) provided with photosensitive active ingredients by means of visually conspicuous aluminized or lacquered covering films as backing layer of the TTS.
WO-Al-00/56289 describes a method for protecting therapeutic preparations, systems or their constituents, the intention being to achieve in each case specific protection from degradation by harmful factors such as atmospheric oxygen, water and/or light.
Photoprotective substances which absorb or reflect electromagnetic waves are used, employing respectively absorbents or reflectants whose absorption or reflection spectrum covers the wavelength range
- 2 -responsible for the instability of the photosensitive substance or its constituents. Coloured plastic films are used inter alia in this case as covering film, indicated by example of the 1,4-dihydropyridine derivative lacidipine.
The colouring of highly flexible plastic films proves to be difficult and does not provide reliable photoprotection owing to the frequently occurring fissures in the coloured layer of the plastic film.
WO-A2-02/34200 further discloses transdermal therapeutic systems (TTS) which consist of an active ingredient-containing polymer matrix and of a backing layer, where polymer matrix and backing layer are firmly connected or form a laminate, and both the polymer matrix and the backing layer comprise a colourless system which absorbs in the UV range but has no intrinsic pharmacological effect.
EP-A1-1452173 indicates transdermai therapeutic ,systems which consist of a backing layer, of at least one .active ingredient-containing matrix and optionally of a Kletachable:film and comprises a Tri= absorber, whereat :least one UV, absorber-containing adhesive layer is . provided between the backing layer and the active ingredient-containing matrix which is furthest away from the surface of the skin, and at least one separating layer which is impermeable to active ingredient and impermeable to the UV absorber is present between the adhesive layer containing the UV
absorber and the active ingredient-containing matrix which is furthest away from the surface of the skin. It is possible in this case to select as UV absorbers the UV absorbers from the group of p-aminobenzoic acid, aminobenzoic acid derivative, preferably 2-ethylhexyl 4-dimethylaminobenzoate and/or polyethoxyethyl 4-bis(polyethoxy)aminobenzoate, cinnamic acid, cinnamic acid derivatives, preferably isoamyl 4-methoxycinnamate and/or 2-ethylhexyl 4-methoxycinnamate,
The colouring of highly flexible plastic films proves to be difficult and does not provide reliable photoprotection owing to the frequently occurring fissures in the coloured layer of the plastic film.
WO-A2-02/34200 further discloses transdermal therapeutic systems (TTS) which consist of an active ingredient-containing polymer matrix and of a backing layer, where polymer matrix and backing layer are firmly connected or form a laminate, and both the polymer matrix and the backing layer comprise a colourless system which absorbs in the UV range but has no intrinsic pharmacological effect.
EP-A1-1452173 indicates transdermai therapeutic ,systems which consist of a backing layer, of at least one .active ingredient-containing matrix and optionally of a Kletachable:film and comprises a Tri= absorber, whereat :least one UV, absorber-containing adhesive layer is . provided between the backing layer and the active ingredient-containing matrix which is furthest away from the surface of the skin, and at least one separating layer which is impermeable to active ingredient and impermeable to the UV absorber is present between the adhesive layer containing the UV
absorber and the active ingredient-containing matrix which is furthest away from the surface of the skin. It is possible in this case to select as UV absorbers the UV absorbers from the group of p-aminobenzoic acid, aminobenzoic acid derivative, preferably 2-ethylhexyl 4-dimethylaminobenzoate and/or polyethoxyethyl 4-bis(polyethoxy)aminobenzoate, cinnamic acid, cinnamic acid derivatives, preferably isoamyl 4-methoxycinnamate and/or 2-ethylhexyl 4-methoxycinnamate,
3-benzylidenebornan-2-one, benzylidenebornan72-pne derivatives, preferably 3-(4')-methylhenzylidenebornan-2-one, 3-(4-sulphone)benzylidenebornan-2-one and/or 3-(4'-trimethylammonium)benzylidenebornan-2-one methyl-sulphate, salicylic acid derivative, preferably 4-iso-propylbenzyl salicylate, 2-ethylhexyl salicylate, and/or 3,3,5-trimethylcyclohexyl salicylate, benzo-triazoles, preferably 2-(5-chloro-2H-benzotriazol-2-y1)-6-(1,1-dimethylethyl)-4-methylphenol, 2,4,6'-tri-aniline-p-(carbo-2'-ethylhexyl-l'-oxy)-1,3,5-triazine, 3-imidazol-4-ylacrylic acid, 3-imidazol-4-y1-3-imidazol-4-ylacrylic ester, 2-phenylenebenzimidazole-5-sulphonic acid and/or their K, Na and triethanolamine (=TEA) salts, 2-cyano-3,3-diphenylacrylic acid, terephthaloylidenedicamphorsulphonic acid, butyl-methoxydibenzoylmethane, benzophenone and/or benzo-phenone derivatives, preferably benzophenone-3 and/or benzophenone-4.
The known solutions have the disadvantage - that the protective effect produced by the added UV absorber for the active ingredient is incomplete, - that owing to the incomplete protective effect in some cases higher concentrations of UV absorbers must be employed, which may have adverse effects on the compatibility of the TTS with skin.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is a graphical illustration showing the percentage of photosensitive active ingredient remaining in a transdermal therapeutic system according to the invention with photo-protective features and the percentage of photosensitive active ingredient remaining in a comparative transdermal therapeutic system; and Figures 2 to 4 are respective diagrammatic cross-sectional views through various embodiments of the - 3a -transdermal therapeutic systems according to the invention.
Summary of the invention It is therefore an object of the invention to provide a pharmaceutical preparation which is provided with a photosensitive active ingredient and is to be administered transdermally, and which ensures an increased protective effect for the active ingredient on use of a minimal UV absorber concentration which avoids the aforementioned disadvantages.
The object is achieved according to the invention by a solid transdermal therapeutic system with UV absorber.
The known solutions have the disadvantage - that the protective effect produced by the added UV absorber for the active ingredient is incomplete, - that owing to the incomplete protective effect in some cases higher concentrations of UV absorbers must be employed, which may have adverse effects on the compatibility of the TTS with skin.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is a graphical illustration showing the percentage of photosensitive active ingredient remaining in a transdermal therapeutic system according to the invention with photo-protective features and the percentage of photosensitive active ingredient remaining in a comparative transdermal therapeutic system; and Figures 2 to 4 are respective diagrammatic cross-sectional views through various embodiments of the - 3a -transdermal therapeutic systems according to the invention.
Summary of the invention It is therefore an object of the invention to provide a pharmaceutical preparation which is provided with a photosensitive active ingredient and is to be administered transdermally, and which ensures an increased protective effect for the active ingredient on use of a minimal UV absorber concentration which avoids the aforementioned disadvantages.
The object is achieved according to the invention by a solid transdermal therapeutic system with UV absorber.
- 4 -The UV-stable TTS consists in its sequence of layers in this case of a backing layer 1, of at least one active ingredient-containing matrix 2 and of a detachable protective film 3, it optionally being for an adhesive layer 4 and a separating layer 5 to be introduced between the backing layer 1 and the active ingredient-containing matrix 2. UV absorbers from the group of hydroxyphenyltriazines can be embedded in the backing layer 1 or in the active ingredient-containing matrix 2 or in the adhesive layer 4.
It is possible according to the invention for the UV
absorber to be 2,4-bis-[4-(2-ethylhexyloxy)-2-hydroxy]pheny1-6-(4-methoxypheny1)-(1,3,5)-triazine.
It is furthermore possible according to the invention for the weight per unit area of the matrix 2 to be from 30 to 150 g/m2. In this connection, a weight per unit area of from 50 to 120 g/m2 is preferred, and of 100 g/m2 is particularly preferred.
It is also possible in the solid transdermal therapeutic system according to the invention for the weight per unit area of the adhesive layer 4 to be from
It is possible according to the invention for the UV
absorber to be 2,4-bis-[4-(2-ethylhexyloxy)-2-hydroxy]pheny1-6-(4-methoxypheny1)-(1,3,5)-triazine.
It is furthermore possible according to the invention for the weight per unit area of the matrix 2 to be from 30 to 150 g/m2. In this connection, a weight per unit area of from 50 to 120 g/m2 is preferred, and of 100 g/m2 is particularly preferred.
It is also possible in the solid transdermal therapeutic system according to the invention for the weight per unit area of the adhesive layer 4 to be from
5 to 50 g/m2. In this connection, a weight per unit area of from 20 to 30 g/m2 is preferred.
The UV absorber can be present according to the invention in the adhesive layer 4 in the concentration of from 0.5 to 5% (m/m) in dissolved form. In this connection, a concentration of from 1.0 to 4.0% is preferred, and of from 1.5 to 3.0% is particularly preferred.
The matrix 2 and/or the adhesive layer 4 in the solid transdermal therapeutic system can furthermore be designed according to the invention to be self-adhesive and to consist substantially of polymers which are selected from the groups = of polyisobutylene, polybutene, polyacrylate, polydimethylsiloxane, styrene-isoprene block polymer or polyisoprene.
It is also possible in the solid transdermal therapeutic system according to the invention for the separating layer 5 to have a layer thickness of from 4 to 23 pm. In this connection, the layer thickness of from 4 to 10 pm is preferred.
It is possible according to the invention in the solid transdermal therapeutic system for separating layer 5 to be impermeable to active ingredient and impermeable to the UV absorber.
It is furthermore possible according to the invention for the separating layer 5 in the solid transdermal therapeutic system to consist of a barrier polymer.
Preference is given in this connection to polyethylene terephthalate or polyacrylonitrile or polyvinyl_ chloride or polyvinylidene chloride or its copolymers or colaminates.
It is also possible in the solid transdermai therapeutic system according to the invention for the backing layer 1 to be permeable to active ingredient and to consist of polypropylene, polyethylene, polyurethane, ethylene-vinyl acetate copolymer or of a multilayer composite of these materials with one another or with other materials.
The UV absorber(s) in the solid transdermal therapeutic system may according to the invention be colourless or yellowish.
It is furthermore possible for the solid transdermal therapeutic system according to the invention to be transparent or slightly opaque.
It is also possible for at least one hormone to be
The UV absorber can be present according to the invention in the adhesive layer 4 in the concentration of from 0.5 to 5% (m/m) in dissolved form. In this connection, a concentration of from 1.0 to 4.0% is preferred, and of from 1.5 to 3.0% is particularly preferred.
The matrix 2 and/or the adhesive layer 4 in the solid transdermal therapeutic system can furthermore be designed according to the invention to be self-adhesive and to consist substantially of polymers which are selected from the groups = of polyisobutylene, polybutene, polyacrylate, polydimethylsiloxane, styrene-isoprene block polymer or polyisoprene.
It is also possible in the solid transdermal therapeutic system according to the invention for the separating layer 5 to have a layer thickness of from 4 to 23 pm. In this connection, the layer thickness of from 4 to 10 pm is preferred.
It is possible according to the invention in the solid transdermal therapeutic system for separating layer 5 to be impermeable to active ingredient and impermeable to the UV absorber.
It is furthermore possible according to the invention for the separating layer 5 in the solid transdermal therapeutic system to consist of a barrier polymer.
Preference is given in this connection to polyethylene terephthalate or polyacrylonitrile or polyvinyl_ chloride or polyvinylidene chloride or its copolymers or colaminates.
It is also possible in the solid transdermai therapeutic system according to the invention for the backing layer 1 to be permeable to active ingredient and to consist of polypropylene, polyethylene, polyurethane, ethylene-vinyl acetate copolymer or of a multilayer composite of these materials with one another or with other materials.
The UV absorber(s) in the solid transdermal therapeutic system may according to the invention be colourless or yellowish.
It is furthermore possible for the solid transdermal therapeutic system according to the invention to be transparent or slightly opaque.
It is also possible for at least one hormone to be
- 6 -active as active ingredient in the solid transdermal therapeutic system according to the invention.
It is possible according to the invention for the active pharmaceutical ingredients to be a progestogen.
Preference is given in this case to gestodene or levonorgestrol.
It is furthermore possible to add an estrogen to the progestogen in the solid transdermal therapeutic system according to the invention. Preference is given in this case to ethynylestradiol.
It is also possible according to the invention for the solid transdermal therapeutic system to be used in fertility control.
It is further possible according to the invention to use one. or, more UV absorbers from the group of . the hydroxyphenyltriazines for producing a solid trandermal system, whose sequence of layers consists of at least three layers, this sequence of layers starting furthest =
away from the skin with a backing layer 1, an at least monolayer active ingredient-containing matrix 2, a detachable protective film 3 and optionally, introduced between backing layer 1 and active ingredient-containing matrix 2, an adhesive layer 4 and separating layer 5 following the active ingredient-containing matrix 2 for fertility control, and where the UV
absorber(s) from the group of hydroxyphenyltriazines is/are embedded in the backing layer 1 or in the active ingredient-containing matrix 2 or in the adhesive layer 4.
It is also possible according to the invention for the solid transdermal therapeutic system to be equipped without a membrane controlling active ingredient release.
It is possible according to the invention for the active pharmaceutical ingredients to be a progestogen.
Preference is given in this case to gestodene or levonorgestrol.
It is furthermore possible to add an estrogen to the progestogen in the solid transdermal therapeutic system according to the invention. Preference is given in this case to ethynylestradiol.
It is also possible according to the invention for the solid transdermal therapeutic system to be used in fertility control.
It is further possible according to the invention to use one. or, more UV absorbers from the group of . the hydroxyphenyltriazines for producing a solid trandermal system, whose sequence of layers consists of at least three layers, this sequence of layers starting furthest =
away from the skin with a backing layer 1, an at least monolayer active ingredient-containing matrix 2, a detachable protective film 3 and optionally, introduced between backing layer 1 and active ingredient-containing matrix 2, an adhesive layer 4 and separating layer 5 following the active ingredient-containing matrix 2 for fertility control, and where the UV
absorber(s) from the group of hydroxyphenyltriazines is/are embedded in the backing layer 1 or in the active ingredient-containing matrix 2 or in the adhesive layer 4.
It is also possible according to the invention for the solid transdermal therapeutic system to be equipped without a membrane controlling active ingredient release.
- 7 -The transdermal therapeutic system according to the invention has the following advantages compared with conventional systems with photosensitive active ingredient content:
- The protective effect provided by the UV absorber from the group of hydroxyphenyltriazines is enhanced and - the concentration of the UV absorber from the group of hydroxyphenyltriazines which is necessary to achieve a protective effect is reduced.
- It is =thus possible in particular to avoid or reduce the risk of possible skin irritation.
Exemplary embodiments The invention is explained further by the following examples.
Example 1 Two formulations of a photosensitive active ingredient from the group of progestogens= wera prepared.
Formulation 2 comprises an adhesive layer and a separating layer, and the adhesive layer comprises 2.5%
by weight of a UV-absorbing substance from the class of the hydroxyphenyltriazines.
Formulation 1 comprises no adhesive layer and separating layer and serves as comparative formulation.
Both formulations comprise an active ingredient-containing matrix with a photosensitive progestogen and are equipped with a backing layer of polyethylene, resulting in a TTS in each case.
Formulation 2 has the following composition:
1. Active ingredient-containing matrix:
- 1.9% progestogen - 98.1% polyisobutylene-based adhesive 2. Adhesive layer:
- 2.5% Tinosorb S
- 97.2% polyisobutylene-based adhesive
- The protective effect provided by the UV absorber from the group of hydroxyphenyltriazines is enhanced and - the concentration of the UV absorber from the group of hydroxyphenyltriazines which is necessary to achieve a protective effect is reduced.
- It is =thus possible in particular to avoid or reduce the risk of possible skin irritation.
Exemplary embodiments The invention is explained further by the following examples.
Example 1 Two formulations of a photosensitive active ingredient from the group of progestogens= wera prepared.
Formulation 2 comprises an adhesive layer and a separating layer, and the adhesive layer comprises 2.5%
by weight of a UV-absorbing substance from the class of the hydroxyphenyltriazines.
Formulation 1 comprises no adhesive layer and separating layer and serves as comparative formulation.
Both formulations comprise an active ingredient-containing matrix with a photosensitive progestogen and are equipped with a backing layer of polyethylene, resulting in a TTS in each case.
Formulation 2 has the following composition:
1. Active ingredient-containing matrix:
- 1.9% progestogen - 98.1% polyisobutylene-based adhesive 2. Adhesive layer:
- 2.5% Tinosorb S
- 97.2% polyisobutylene-based adhesive
- 8 -Tinosorb S (from Ciba, Lampertheim) is a UV absorber of the hydroxyphenyltriazine class.
To investigate the photoprotective effect, both formulations were irradiated with light having a UV
spectrum of 300-800 nm for a period of up to 34 h. The radiation source used was a xenon lamp. A filter system (type: Suprax filter) was placed between the radiation source and the samples to be irradiated in order to simulate irradiation under realistic conditions of use of the TTS. The active ingredient content in the TTS
was then determined. It revealed that the TTS of formulation 2 which comprised an adhesive layer with UV-absorbing substance and a separating layer still comprised more than 95% of the originally employed amount of the photosensitive active ingredient after irradiation for 34 h, whereas the TTS of formulation 1 comprised only about 3% of the originally employed amount of the photosensitive active ingredient after irradiation (Fig. 1). This demonstrates that the system according to the invention displays an improved protection from the sun under realistic conditions of use. because the UV-protective. effect of the system .
according to the invention (formulation 2) was.
considerably greater than that of the comparative system (formulation 1).
Example 2 Formulation with a photosensitive active ingredient from the group of progestogens with in each case an adhesive layer and separating layer, in which the separating layer consists of polyethylene terephthalate (Hostaphan , from Mitsubishi Polyester, Wiesbaden).
The formulation has the following composition:
1. Active ingredient-containing matrix - 1.9% progestogen - 98.1% polyisobutylene-based adhesive 2. Adhesive layer 1 and 2:
- 2.5% Tinosorb S
To investigate the photoprotective effect, both formulations were irradiated with light having a UV
spectrum of 300-800 nm for a period of up to 34 h. The radiation source used was a xenon lamp. A filter system (type: Suprax filter) was placed between the radiation source and the samples to be irradiated in order to simulate irradiation under realistic conditions of use of the TTS. The active ingredient content in the TTS
was then determined. It revealed that the TTS of formulation 2 which comprised an adhesive layer with UV-absorbing substance and a separating layer still comprised more than 95% of the originally employed amount of the photosensitive active ingredient after irradiation for 34 h, whereas the TTS of formulation 1 comprised only about 3% of the originally employed amount of the photosensitive active ingredient after irradiation (Fig. 1). This demonstrates that the system according to the invention displays an improved protection from the sun under realistic conditions of use. because the UV-protective. effect of the system .
according to the invention (formulation 2) was.
considerably greater than that of the comparative system (formulation 1).
Example 2 Formulation with a photosensitive active ingredient from the group of progestogens with in each case an adhesive layer and separating layer, in which the separating layer consists of polyethylene terephthalate (Hostaphan , from Mitsubishi Polyester, Wiesbaden).
The formulation has the following composition:
1. Active ingredient-containing matrix - 1.9% progestogen - 98.1% polyisobutylene-based adhesive 2. Adhesive layer 1 and 2:
- 2.5% Tinosorb S
- 9 -- 97.5% polyacrylate-based adhesive Example 3 Formulation with a photosensitive active ingredient from the group of progestogens with in each case two adhesive layers and separating layers, in which the separating layers consist of polyethylene terephthalate (Hostaphan , from Mitsubishi Polyester, Wiesbaden).
Formulation I has the following composition:
1. Active ingredient-containing matrix:
- 1.9% progestogen - 98.1% polyisobutylene-based adhesive 2. Adhesive layer 1 and 2:
- 3% Tinuvin 400 - 97% polyacrylate-based adhesive Tinuvin 400 (from Ciba, Lampertheim) is a UV absorber of the hydroxyphenyltriazine class.
Example 4 to 12 Formulation with a photosensitive active ingredient .
from the group of progestogens with in each case at least one adhesive layer and separating layer, in which the active ingredient-containing matrix is embodied in analogy to Examples 1 to 3, and the adhesive layer comprises a polyisobutylene-based adhesive and has the compositions mentioned below.
Compo- Example sition of the adhe- 4 5 6 7 8 9 10 11 12 sive layer Tinosorb''S 2 2 2 3 3 3 4 4 4 [%1 Polyiso- 98 98 98 97 97 97 96 96 96 butylene-, based adhesive [%1 Weight per 20 30 50 20 30 50 20 30 50 unit area [g/m2]
Example 13 to 21 ¨ 10 -Formulation with a photosensitive active ingredient from the group of progestogens with in each case at least one adhesive layer and separating layer, in which the active ingredient-containing matrix is embodied in analogy to Examples 1 to 3, and the adhesive layer comprises a polyacrylate-based adhesive and has the compositions mentioned below.
Compo- Example sition of the adhe- 13 14 15 16 17 18 19 20 sive layer TinosorbS 2 2 2 3 3 3 4 4 4 1%]
Poly- 98 98 98 97 97 97 96 96 96 acrylate-based adhesive 1%]
Weight per 20 30 50 20 30 50 20 30 50 unit area [g/m2]
Formulation I has the following composition:
1. Active ingredient-containing matrix:
- 1.9% progestogen - 98.1% polyisobutylene-based adhesive 2. Adhesive layer 1 and 2:
- 3% Tinuvin 400 - 97% polyacrylate-based adhesive Tinuvin 400 (from Ciba, Lampertheim) is a UV absorber of the hydroxyphenyltriazine class.
Example 4 to 12 Formulation with a photosensitive active ingredient .
from the group of progestogens with in each case at least one adhesive layer and separating layer, in which the active ingredient-containing matrix is embodied in analogy to Examples 1 to 3, and the adhesive layer comprises a polyisobutylene-based adhesive and has the compositions mentioned below.
Compo- Example sition of the adhe- 4 5 6 7 8 9 10 11 12 sive layer Tinosorb''S 2 2 2 3 3 3 4 4 4 [%1 Polyiso- 98 98 98 97 97 97 96 96 96 butylene-, based adhesive [%1 Weight per 20 30 50 20 30 50 20 30 50 unit area [g/m2]
Example 13 to 21 ¨ 10 -Formulation with a photosensitive active ingredient from the group of progestogens with in each case at least one adhesive layer and separating layer, in which the active ingredient-containing matrix is embodied in analogy to Examples 1 to 3, and the adhesive layer comprises a polyacrylate-based adhesive and has the compositions mentioned below.
Compo- Example sition of the adhe- 13 14 15 16 17 18 19 20 sive layer TinosorbS 2 2 2 3 3 3 4 4 4 1%]
Poly- 98 98 98 97 97 97 96 96 96 acrylate-based adhesive 1%]
Weight per 20 30 50 20 30 50 20 30 50 unit area [g/m2]
Claims (27)
1. A solid transdermal therapeutic system (TTS) with a UV
absorber, said solid transdermal therapeutic system comprising a sequence of at least three layers;
wherein said at least three layers comprise a backing layer, at least one active ingredient-containing matrix, and a detachable protective film;
wherein optionally an adhesive layer and a separating layer are present between the backing layer and the at least one active ingredient-containing matrix; and wherein said UV absorber comprises at least one hydroxy-phenyltriazine compound and said UV absorber is embedded in the backing layer, in the at least one active ingredient-containing matrix, or in the adhesive layer.
absorber, said solid transdermal therapeutic system comprising a sequence of at least three layers;
wherein said at least three layers comprise a backing layer, at least one active ingredient-containing matrix, and a detachable protective film;
wherein optionally an adhesive layer and a separating layer are present between the backing layer and the at least one active ingredient-containing matrix; and wherein said UV absorber comprises at least one hydroxy-phenyltriazine compound and said UV absorber is embedded in the backing layer, in the at least one active ingredient-containing matrix, or in the adhesive layer.
2. The solid transdermal therapeutic system as defined in claim 1, wherein said at least one hydroxyphenyltriazine compound is 2,4-bis-([4-(2'-ethylhexyloxy)-2-hydroxy]phenyl)-6-(4-methoxyphenyl)-(1,3,5)-triazine.
3. The solid transdermal therapeutic system as defined in claim 1 or 2, wherein the at least one active ingredient-containing matrix has a weight per unit area of from 30 to 150 g/m2.
4. The solid transdermal therapeutic system as defined in claim 3, wherein the weight per unit area is from 50 to 120 g/m2.
5. The solid transdermal therapeutic system as defined in any one of claims 1 to 4, wherein the adhesive layer has a weight per unit area of from 5 to 50 g/m2.
6. The solid transdermal therapeutic system as defined in claim 5, wherein the weight per unit area is from 20 to 30 g/m2.
7. The solid transdermal therapeutic system, as defined in any one of claims 1 to 6, wherein said UV absorber is present in a concentration of from 0.5 to 5% (m/m) in dissolved form in the adhesive layer.
8. The solid transdermal therapeutic system as defined in claim 7, wherein said concentration of said UV absorber is from 1.0 to 4.0% (m/m).
9. The solid transdermal therapeutic system as defined in any one of claims 1 to 8, wherein the at least one active ingredient-containing matrix and the adhesive layer are self-adhesive and substantially consist of at least one polymer;
wherein said at least one polymer is polyisobutylene, polybutene, polyacrylate, polydimethyl-siloxane, styrene-isoprene block polymers or polyisoprene, or any combination thereof.
wherein said at least one polymer is polyisobutylene, polybutene, polyacrylate, polydimethyl-siloxane, styrene-isoprene block polymers or polyisoprene, or any combination thereof.
10. The solid transdermal therapeutic system as defined in any one of claims 1 to 9, wherein said separating layer has a layer thickness of from 4 to 23 µm.
11. The solid transdermal therapeutic system as defined in claim 10, wherein said layer thickness is from 4 to 10 µm.
12. The solid transdermal therapeutic system as defined in any one of claims 1 to 11, wherein said at least one active ingredient-containing matrix contains an active pharmaceutical ingredient and said separating layer is impermeable to said active pharmaceutical ingredient and impermeable to said UV absorber.
13. The solid transdermal therapeutic system as defined in any one of claims 1 to 12, wherein said separating layer consists of a barrier polymer and said barrier polymer is polyethylene terephthalate, polyacrylonitrile, polyvinyl chloride, polyvinylidene chloride, or a copolymer or co-laminate thereof.
14. The solid transdermal therapeutic system as defined in any one of claims 1 to 13, wherein said at least one active ingredient-containing matrix contains an active pharmaceutical ingredient, said backing layer is permeable to said active pharmaceutical ingredient and said backing layer consists of polypropylene, polyethylene, polyurethane, ethylene-vinyl acetate copolymer, or a multilayer composite of the foregoing polymers with one another.
15. The solid transdermal therapeutic system as defined in any one of claims 1 to 14, wherein said UV absorber is colorless or yellowish.
16. The solid transdermal therapeutic system as defined in any one of claims 1 to 15, which is transparent or slightly opaque.
17. The solid transdermal therapeutic system as defined in any one of claims 1 to 16, which further comprises an active pharmaceutical ingredient, wherein said active pharmaceutical ingredient comprises at least one hormone.
18. The solid transdermal therapeutic system as defined in claim 17, wherein said active pharmaceutical ingredient is a progestogen.
19. The solid transdermal therapeutic system as defined in claim 18, wherein said progestogen is gestodene or levonorgestrel.
20. The solid transdermal therapeutic system as defined in claim 18, consisting of a fertility controlling preparation.
21. The solid transdermal therapeutic system as defined in claim 17, wherein said active pharmaceutical ingredient comprises a progestogen and an estrogen.
22. The solid transdermal therapeutic system as defined in claim 21, consisting of a fertility controlling preparation.
23. The solid transdermal therapeutic system as defined in claim 21, wherein said progestogen is gestodene and said estrogen is ethinyl estradiol.
24. The solid transdermal therapeutic system as defined in any one of claims 1 to 16, further comprising an active pharmaceutical ingredient, and wherein a membrane controlling release of the active pharmaceutical ingredient is absent.
25. The solid transdermal therapeutic system as defined in any one of claims 1 to 16, further comprising an active pharmaceutical ingredient, wherein said active pharmaceutical ingredient comprises gestodene and ethinyl estradiol.
26. The solid transdermal therapeutic system as defined in any one of claims 1 to 25, wherein said separating layer consists of polyethylene terephthalate.
27. The solid transdermal therapeutic system as defined in any one of claims 1 to 26, wherein said backing layer is polyethylene.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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EP05009579.3 | 2005-05-02 | ||
EP05009579A EP1719504A1 (en) | 2005-05-02 | 2005-05-02 | Solid transdermal therapeutic system with UV-absorber |
PCT/EP2006/003959 WO2006117139A2 (en) | 2005-05-02 | 2006-04-28 | Solid transdermal therapeutic system comprising uv absorber |
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CA2605112A1 CA2605112A1 (en) | 2006-11-09 |
CA2605112C true CA2605112C (en) | 2013-11-05 |
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---|---|---|---|
CA2605112A Expired - Fee Related CA2605112C (en) | 2005-05-02 | 2006-04-28 | Solid transdermal therapeutic system comprising uv absorber |
Country Status (26)
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EP (2) | EP1719504A1 (en) |
JP (2) | JP5360877B2 (en) |
KR (2) | KR101351161B1 (en) |
CN (2) | CN101171001A (en) |
AR (1) | AR055927A1 (en) |
AU (1) | AU2006243442A1 (en) |
BR (1) | BRPI0611087A2 (en) |
CA (1) | CA2605112C (en) |
CR (1) | CR9483A (en) |
CY (1) | CY1115757T1 (en) |
DK (1) | DK1879560T3 (en) |
DO (1) | DOP2006000100A (en) |
EA (1) | EA200702344A1 (en) |
ES (1) | ES2523663T3 (en) |
GT (1) | GT200600183A (en) |
IL (1) | IL186945A0 (en) |
MX (1) | MX2007013779A (en) |
NO (1) | NO20076187L (en) |
PE (1) | PE20061414A1 (en) |
PL (1) | PL1879560T3 (en) |
PT (1) | PT1879560E (en) |
SI (1) | SI1879560T1 (en) |
TW (1) | TW200719902A (en) |
UY (1) | UY29511A1 (en) |
WO (1) | WO2006117139A2 (en) |
ZA (1) | ZA200710418B (en) |
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EP1594483B1 (en) | 2003-02-21 | 2006-07-19 | Schering AG | Uv stable transdermal therapeutic plaster |
US8668925B2 (en) | 2003-12-12 | 2014-03-11 | Bayer Intellectual Property Gmbh | Transdermal delivery of hormones without the need of penetration enhancers |
US8962013B2 (en) | 2005-05-02 | 2015-02-24 | Bayer Intellectual Property Gmbh | Multi-layered transdermal system with triazine UV absorber |
EP2613772B1 (en) * | 2010-09-06 | 2016-12-14 | Bayer Intellectual Property GmbH | Low-dose transdermal patches with high drug release |
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US5023084A (en) * | 1986-12-29 | 1991-06-11 | Rutgers, The State University Of New Jersey | Transdermal estrogen/progestin dosage unit, system and process |
DE59107052D1 (en) * | 1990-03-30 | 1996-01-25 | Ciba Geigy Ag | Paint compositions |
US8173592B1 (en) * | 1999-03-31 | 2012-05-08 | Zentaris Ivf Gmbh | Method for a programmed controlled ovarian stimulation protocol |
US7384650B2 (en) * | 1999-11-24 | 2008-06-10 | Agile Therapeutics, Inc. | Skin permeation enhancement composition for transdermal hormone delivery system |
BRPI0109198B8 (en) | 2000-03-17 | 2021-05-25 | Hisamitsu Pharmaceutical Co | plaster having a support |
EP1594483B1 (en) * | 2003-02-21 | 2006-07-19 | Schering AG | Uv stable transdermal therapeutic plaster |
EP1452173A1 (en) * | 2003-02-25 | 2004-09-01 | Schering AG | UV-stable transdermal patch |
DE602004019230D1 (en) * | 2003-09-11 | 2009-03-12 | Ciba Holding Inc | WATER BASED CONCENTRATED PRODUCT FORMS OF LIGHT PROTECTION PRODUCED BY HETEROPHASE POLYMERIZATION TECHNOLOGY |
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2005
- 2005-05-02 EP EP05009579A patent/EP1719504A1/en not_active Withdrawn
-
2006
- 2006-04-28 WO PCT/EP2006/003959 patent/WO2006117139A2/en active Application Filing
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- 2006-04-28 ES ES06753441.2T patent/ES2523663T3/en active Active
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- 2006-04-28 KR KR1020077025388A patent/KR101351161B1/en active IP Right Grant
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- 2006-04-28 CN CN201810889234.4A patent/CN108969507A/en not_active Withdrawn
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- 2006-04-28 EP EP06753441.2A patent/EP1879560B1/en active Active
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2007
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2013
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