CN102596438A - 透皮治疗系统中药物活性物质的销毁性处理 - Google Patents
透皮治疗系统中药物活性物质的销毁性处理 Download PDFInfo
- Publication number
- CN102596438A CN102596438A CN201080034897XA CN201080034897A CN102596438A CN 102596438 A CN102596438 A CN 102596438A CN 201080034897X A CN201080034897X A CN 201080034897XA CN 201080034897 A CN201080034897 A CN 201080034897A CN 102596438 A CN102596438 A CN 102596438A
- Authority
- CN
- China
- Prior art keywords
- composition
- reagent
- layer
- tts
- polyester
- 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.)
- Granted
Links
- 230000001225 therapeutic effect Effects 0.000 title claims abstract description 8
- 239000004480 active ingredient Substances 0.000 title abstract 2
- 230000001066 destructive effect Effects 0.000 title abstract 2
- 239000010410 layer Substances 0.000 claims abstract description 17
- 239000011241 protective layer Substances 0.000 claims abstract description 9
- 239000000835 fiber Substances 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 35
- 239000003153 chemical reaction reagent Substances 0.000 claims description 27
- 239000013543 active substance Substances 0.000 claims description 20
- -1 polytetrafluoroethylene Polymers 0.000 claims description 18
- 230000006378 damage Effects 0.000 claims description 13
- 229920000642 polymer Polymers 0.000 claims description 9
- 238000010276 construction Methods 0.000 claims description 8
- 229920000728 polyester Polymers 0.000 claims description 8
- 239000013047 polymeric layer Substances 0.000 claims description 8
- 229920001343 polytetrafluoroethylene Polymers 0.000 claims description 8
- 239000004810 polytetrafluoroethylene Substances 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 7
- 239000004698 Polyethylene Substances 0.000 claims description 6
- 239000004743 Polypropylene Substances 0.000 claims description 6
- 239000004744 fabric Substances 0.000 claims description 6
- 229920000058 polyacrylate Polymers 0.000 claims description 6
- 229920000573 polyethylene Polymers 0.000 claims description 6
- 229920001155 polypropylene Polymers 0.000 claims description 6
- 229920000193 polymethacrylate Polymers 0.000 claims description 5
- 239000012286 potassium permanganate Substances 0.000 claims description 5
- 239000004952 Polyamide Substances 0.000 claims description 4
- 239000004642 Polyimide Substances 0.000 claims description 4
- 239000004793 Polystyrene Substances 0.000 claims description 4
- 239000000853 adhesive Substances 0.000 claims description 4
- 230000001070 adhesive effect Effects 0.000 claims description 4
- 229920002647 polyamide Polymers 0.000 claims description 4
- 229920001721 polyimide Polymers 0.000 claims description 4
- 229920002223 polystyrene Polymers 0.000 claims description 4
- 229920000915 polyvinyl chloride Polymers 0.000 claims description 4
- 239000004800 polyvinyl chloride Substances 0.000 claims description 4
- AZFNGPAYDKGCRB-XCPIVNJJSA-M [(1s,2s)-2-amino-1,2-diphenylethyl]-(4-methylphenyl)sulfonylazanide;chlororuthenium(1+);1-methyl-4-propan-2-ylbenzene Chemical compound [Ru+]Cl.CC(C)C1=CC=C(C)C=C1.C1=CC(C)=CC=C1S(=O)(=O)[N-][C@@H](C=1C=CC=CC=1)[C@@H](N)C1=CC=CC=C1 AZFNGPAYDKGCRB-XCPIVNJJSA-M 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 claims description 3
- 239000004033 plastic Substances 0.000 claims description 3
- 229920003023 plastic Polymers 0.000 claims description 3
- 235000010289 potassium nitrite Nutrition 0.000 claims description 3
- 239000004304 potassium nitrite Substances 0.000 claims description 3
- 229920000742 Cotton Polymers 0.000 claims description 2
- 241001465754 Metazoa Species 0.000 claims description 2
- 229920002367 Polyisobutene Polymers 0.000 claims description 2
- 229920002396 Polyurea Polymers 0.000 claims description 2
- 239000010425 asbestos Substances 0.000 claims description 2
- 239000011521 glass Substances 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 229920003052 natural elastomer Polymers 0.000 claims description 2
- 229920005615 natural polymer Polymers 0.000 claims description 2
- 239000000025 natural resin Substances 0.000 claims description 2
- 229920001194 natural rubber Polymers 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- 229920001289 polyvinyl ether Polymers 0.000 claims description 2
- 229910052895 riebeckite Inorganic materials 0.000 claims description 2
- 239000003381 stabilizer Substances 0.000 claims description 2
- 229920003051 synthetic elastomer Polymers 0.000 claims description 2
- 229920001059 synthetic polymer Polymers 0.000 claims description 2
- 229920003002 synthetic resin Polymers 0.000 claims description 2
- 239000000057 synthetic resin Substances 0.000 claims description 2
- 239000005061 synthetic rubber Substances 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims 1
- 235000011837 pasties Nutrition 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 22
- 239000011149 active material Substances 0.000 description 14
- 229940079593 drug Drugs 0.000 description 7
- 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 description 6
- 239000000463 material Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 description 4
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 description 4
- 229960001736 buprenorphine Drugs 0.000 description 4
- 229960001344 methylphenidate Drugs 0.000 description 4
- 239000011505 plaster Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229960003604 testosterone Drugs 0.000 description 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 238000000151 deposition Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 229960002428 fentanyl Drugs 0.000 description 2
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 208000011117 substance-related disease Diseases 0.000 description 2
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical group CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 229920003043 Cellulose fiber Polymers 0.000 description 1
- 229910052684 Cerium Inorganic materials 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- 241000446313 Lamella Species 0.000 description 1
- IDBPHNDTYPBSNI-UHFFFAOYSA-N N-(1-(2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)ethyl)-4-(methoxymethyl)-4-piperidyl)propionanilide Chemical compound C1CN(CCN2C(N(CC)N=N2)=O)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 IDBPHNDTYPBSNI-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000012042 active reagent Substances 0.000 description 1
- 239000012790 adhesive layer Substances 0.000 description 1
- 239000000464 adrenergic agent Substances 0.000 description 1
- 229960001391 alfentanil Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037058 blood plasma level Effects 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- GWXLDORMOJMVQZ-UHFFFAOYSA-N cerium Chemical compound [Ce] GWXLDORMOJMVQZ-UHFFFAOYSA-N 0.000 description 1
- ZCDOYSPFYFSLEW-UHFFFAOYSA-N chromate(2-) Chemical compound [O-][Cr]([O-])(=O)=O ZCDOYSPFYFSLEW-UHFFFAOYSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000000881 depressing effect Effects 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 150000002497 iodine compounds Chemical class 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- HTUMBQDCCIXGCV-UHFFFAOYSA-N lead oxide Chemical compound [O-2].[Pb+2] HTUMBQDCCIXGCV-UHFFFAOYSA-N 0.000 description 1
- 229910000464 lead oxide Inorganic materials 0.000 description 1
- ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical class O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 229920006267 polyester film Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000002444 silanisation Methods 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960004739 sufentanil Drugs 0.000 description 1
- GGCSSNBKKAUURC-UHFFFAOYSA-N sufentanil Chemical compound C1CN(CCC=2SC=CC=2)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 GGCSSNBKKAUURC-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000013271 transdermal drug delivery Methods 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B09—DISPOSAL OF SOLID WASTE; RECLAMATION OF CONTAMINATED SOIL
- B09B—DISPOSAL OF SOLID WASTE NOT OTHERWISE PROVIDED FOR
- B09B3/00—Destroying solid waste or transforming solid waste into something useful or harmless
- B09B3/0075—Disposal of medical waste
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B09—DISPOSAL OF SOLID WASTE; RECLAMATION OF CONTAMINATED SOIL
- B09B—DISPOSAL OF SOLID WASTE NOT OTHERWISE PROVIDED FOR
- B09B2101/00—Type of solid waste
- B09B2101/65—Medical waste
- B09B2101/68—Transdermal patches
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/249921—Web or sheet containing structurally defined element or component
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T442/00—Fabric [woven, knitted, or nonwoven textile or cloth, etc.]
- Y10T442/30—Woven fabric [i.e., woven strand or strip material]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T442/00—Fabric [woven, knitted, or nonwoven textile or cloth, etc.]
- Y10T442/40—Knit fabric [i.e., knit strand or strip material]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T442/00—Fabric [woven, knitted, or nonwoven textile or cloth, etc.]
- Y10T442/60—Nonwoven fabric [i.e., nonwoven strand or fiber material]
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
- Environmental & Geological Engineering (AREA)
- Addiction (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Laminated Bodies (AREA)
Abstract
本发明涉及用于销毁性处理被包含在透皮治疗系统(＝TTS)中的药物活性物质的组合物。所述组合物具有多层构造并包含至少一个其中置入试剂的层和至少一个纤维层。其可进一步还包含保护层。所述根据本发明的组合物与TTS分开地保存。所述分开保存的组合物在TTS经过使用后与之接触。
Description
本发明涉及用于销毁性处理包含在视情况也称为透皮膏药的透皮治疗系统(＝TTS)中的药物活性物质的组合物，所述药物活性物质在下文也简称为药剂。将根据本发明的组合物与使用过的TTS接触，经此所述药剂在化学反应中被销毁或分解，但在所有情况下其药物功效被剥夺。TTS本身通常包含作为药剂的治疗活性物质，优选自镇痛剂类，其从系统中通过扩散加载到皮肤上并随后应用于治疗目的。
在长期治疗中选择用于治疗慢性疼痛的药剂是具有药物活性物质丁丙诺啡和芬太尼的透皮应用。通过持续地经皮释放此类高效镇痛剂以恒定剂量为疼痛患者持续提供较长时间的镇痛剂，以避免血浆峰值和谷值。其优点是，通过低量但足量的活性物质血浆浓度既不会发生归因于过量的副作用也不会发生归因于不足的提供量的可避免的疼痛状态。对于技术人员已知的是例如商购产品
但还有
或
Smat，它们已在疼痛治疗中久经考验。
然而，在疼痛治疗中所述TTS的缺点在于，因为向患者的每天释放，为了维持所谓的浓度梯度并由此为了在TTS应用的整个期间维持就治疗而言所希望的药物活性物质的血浆水平，在TTS中必须总是包含较高储量的活性物质。这导致，经贴敷或使用过的TTS具有被例如毒品消费的相关者滥用的可能。该群体完全有能力收集贴敷过的TTS、提取尚存的残余药物活性物质并为了满足其毒瘾而滥用地摄入。
这样的考虑对于激素睾酮或拟交感神经药哌甲酯也是有意义的。为了避免血浆峰值和谷值，透皮施用这两种药物是有利的，并由此隐含一定的滥用可能，因此例如哌甲酯被世界范围地看作为麻醉药。在美国睾酮如同哌甲酯受相似的法律规定制约。
因此在过去，通过告诫患者剪切贴敷过的膏药并随后通过卫生间引入管道系统来减少无法监控的滥用。该方法的缺点是，通过管道系统大量处理药物产生不可低估的环境问题。此外存在危险，排污管道被TTS的难溶载体材料堵塞。
因此开发了在活性物质之外还同时包含拮抗剂的TTS(例如WO2004/098576、WO 90/04965、WO 2004/037259)。经此，应当阻止了以上所描述的药物活性物质从使用过的TTS中的获取或滥用性提取，至少显著增加了难度。然而，该保护措施被证明不足以用于避免药物滥用，因为始终理论上和甚至用相对简单的制剂可将实质的药物活性物质通过分级化沉淀与拮抗剂分离。
WO 2007/137732描述了一种TTS，其除活性物质之外还包含与活性物质分开、可使活性物质失效的在溶液中的试剂。此外还有一种在TTS使用后清路的介质，以使所述试剂与活性物质发生接触并使后者失效。这种几近完美的溶液的缺点在于，在溶液中的该试剂由于其高反应性限制了其存放能力并且还可能存在在运输时液体溢出导致损坏的风险。
尚未公开的DE 10 2008 016 804建议了在使用后，即经患者从皮肤表面揭除后，其自行销毁的TTS。在所述早期的开发中，自销毁性TTS意味着，在TTS中包含的残余药物活性物质在使用后直接或间接地被销毁、化学分解和/或使之失效。在所建议的实施形式中还尽可能地保证了所述销毁过程不会在TTS的透皮应用之前或期间就发生。然而，该实施形式的缺点是技术繁琐的制造方式，其从经济性角度而言是个问题。
因此本发明的主题是提供一种组合物，其在TTS的常规使用后可靠地并完全地限制了残余药物活性物质的滥用性摄取。此外所述组合物应便于制备并且是长期无问题地可存储的。此外，该组合物是TTS的使用者在高度信赖其功效的同时还应当是易于操作的。
该主题是通过文端所述领域的组合物解决的，其特征性的性质在于其拥有多层构造，其包含至少一层含有储存于其中的试剂的层并包含至少一个纤维层。
在优选的实施形式中，本发明的组合物还进一步包含保护层。其与药剂分开保存。在所述药剂经过使用后，使所述与药剂分开保存的本发明组合物与药剂接触。
在本发明的组合物的层中存储的所述试剂可以是一种物质或物质混合物，其可以根据本发明以固体或膏剂存在。优选所述试剂是与药物活性物质(药剂)化学性反应的并经此将药物活性物质销毁的物质。特别是化学氧化剂例如无机试剂如高锰酸盐如高锰酸钾、二氧化锰、二氧化铅、四乙酸铅、铈(IV)-盐、铬酸盐、四氧化锇、亚硝酸盐如亚硝酸钾、二氧化硒、过氧化物、亚卤化物，或硫；优选其中的高锰酸钾和亚硝酸钾。有机氧化剂例如二甲基砜、N-溴代琥珀酰亚胺、醌、高价碘化合物、过酸和过酯，但也可以同样使用酶。对于给定的药物活性物质，所述试剂优选基于其与给定活性物质的化学反应能力来选择。对于技术人员而言普遍已知的是，何种试剂针对在本发明的意义中的何种药剂是最适合的。
药物活性物质优选涉及选自镇痛剂类的活性物质例如麻醉药。优选提及吗啡衍生物、海洛因和丁丙诺啡、或芬太尼及其衍生物舒芬太尼和阿芬太尼。对于通过TTS的透皮应用是适宜的递送形式的活性物质与试剂的所有其它组合原则上也是可使用的，例如睾酮和哌甲酯。
具有多层构造的本发明的组合物包含至少一个其中置入试剂的层。在此可涉及聚合物层或粘附层。作为聚合物在此可以使用标准聚合物，例如聚酰胺、聚酰亚胺、聚四氟乙烯、聚乙烯、聚丙烯、聚氯乙烯、聚丙烯酸酯或聚甲基丙烯酸酯、聚苯乙烯或聚酯。所述置入使得所述试剂易于从聚合物层再度溶出，用以实现其销毁性处理药剂的注定目的。
作为粘附层，根据本发明使用在室温下无溶剂持久粘性的或保持粘附能力的并且在轻压下基本粘附所有物质的粘附剂。适宜的粘附剂基于例如优选天然或合成的橡胶、聚丙烯酸酯、聚酯、聚氯丁二烯、聚异丁烯、聚乙烯醚或聚脲，其通常与天然或合成的树脂和与氧化稳定剂相组合使用于其常规的目的。在粘附层的情况下通过撒播实现试剂的置入。如此使得试剂易于从粘附层再度溶出。
具有多层构造的根据本发明的组合物进一步包含至少一个纤维层。在此其可以是由矿物纤维如玻璃、石棉、玄武岩，由动物纤维如丝或毛，由植物纤维如棉花或者由源自天然聚合物(如纤维素)和/或合成聚合物的化学纤维构成的织物、针织物或无纺布。作为合成塑料在此可以同样使用如用于聚合物层的标准聚合物，即聚酰胺、聚酰亚胺、聚四氟乙烯、聚乙烯、聚丙烯、聚氯乙烯、聚丙烯酸酯或聚甲基丙烯酸酯、聚苯乙烯或聚酯。
在优选的实施形式中，根据本发明的组合物还包含保护层。所述保护层在此被安置在相对于纤维层的聚合物层另一侧的表面上。作为保护层，根据本发明特别地使用塑料构成的膜，例如聚乙烯、聚丙烯或聚酯。
根据本发明的组合物还可以进一步地包含用于固定保护层的粘合层，其特别有利地是，当其中置入试剂的该层本身不是粘附层。
具有多层构造的、与药剂分开保存的、根据本发明的组合物将出于其注定的使用目的(药物活性物质的销毁性处理)与药剂接触。如下发生：在从患者皮肤揭下透皮膏药/TTS后，将根据本发明的组合物的纤维层用少量液体润湿。随后将贴敷过的TTS粘在根据本发明的具有多层构造的组合物的经湿润的纤维层上。所述液体透过纤维层到达置入聚合物层的试剂，将试剂从那里溶解出来，使得所述试剂通过该纤维层扩散回来，由此与药物活性物质直接接触并将药物活性物质就此化学销毁。
用于销毁性处理TTS中的药物活性物质的具有多层构造的所述根据本发明的组合物适用于所有已知TTS，所述TTS的制备是技术人员原则上由现有技术已知的TTS或透皮膏药的材料、制备方法和构造得知的(就此参见：Transdermale Pflaster；Spektrum der Wissenschaft10/2003，42；Transdermal Controlled Systemic Madications，Y.W.Chien，Drugs and the Pharmaceutical Sciences，Vol.31；Polymersin Transdermal Drug Delivery Systems，S.Kandavilli et.al.，Pharmaceutical Technology，May 2002，62-80)。
本发明将通过以下实施例进一步阐明而非限制于所描述的各个实施形式和物质选择。同样可以特别地，在实施例中描述的、根据本发明组合物的构成单独或彼此组合地用于销毁性处理在TTS中的药物活性物质作为本发明一般化特征的优选特征。
实施例1
将这样的中性聚甲基丙烯酸酯(Plastoid B)份额溶于乙酸乙酯，即用40重量％固体成分产生聚合物溶液。在完全溶解聚合物后在室温下搅拌入相同重量份的细颗粒高锰酸钾形成悬浮液。将如此获得的聚合物溶液用适宜的刮勺加载到硅烷化的聚酯膜上。此后在技术人员已知的实验室干燥箱中于60℃的温度去除溶剂。在溶剂去除后，面重量为180g/m2。
在机械工艺中由经干燥的片层带冲压出各个截段，其具有接近常规商购的
TTS的大小(70×70mm)。随即将该具有经置入的高锰酸钾的聚合物层用纤维素纤维构成的无序纤维无纺布遮盖。
作为测试，将各三个如此制备的本发明的具有多层结构的组合物在包含作为药物活性物质的丁丙诺啡的TTS上就不同的作用时间进行测试。对此将所述无纺布用4.5ml水湿润并在所述经湿润的无纺布上贴敷TTS。在如下表所示的作用时间后将TTS从所述无纺布上分离并用异丙醇加0.1％抗坏血酸溶解残余丁丙诺啡。残余活性物质的量通过高压液相色谱(HPLC)确定。
结果在下表中总结
| 样品 | 作用时间 | 含量[mg/TTS] | 再测得[％] |
| Bph20作为对照 | ./. | 20.3 | 101.3 |
| Bph20 | 0.5h | 17.3 | 86.3 |
| 1h | 16.1 | 80.7 | |
| 2h | 10.5 | 52.5 | |
| 3h | 2.7 | 13.3 | |
| 5h | 0.2 | 1.0 | |
| 6h | 0.2 | 1.0 |
明确显示，在3至4小时的作用时间后不再检出值得一提的量的药物活性物质。由此本发明的组合物完全实现了其销毁性处理的目的并由此有效阻止了滥用和非目的性再利用。
Claims (13)
1.用于销毁性处理被包含在透皮治疗系统(＝TTS)中的药物活性物质的组合物，其特征在于，具有多层构造，包含至少一个其中置入试剂的层和至少一个纤维层。
2.根据权利要求1的组合物，其特征在于，进一步包含保护层。
3.根据权利要求1或2的组合物，其特征在于，与待销毁性处理的药物活性物质分开地保存。
4.根据权利要求1至3任一项的组合物，其特征在于，使所述分开保存的组合物在透皮治疗系统经过使用后与之接触。
5.根据权利要求1至4任一项的组合物，其特征在于，包含固态或糊状形式的试剂。
6.根据权利要求1至5任一项的组合物，其特征在于，所述试剂是氧化剂。
7.根据权利要求1至6任一项的组合物，其特征在于，所述试剂是高锰酸钾或亚硝酸钾。
8.根据权利要求1至7任一项的组合物，其特征在于，所述其中置入试剂的层是其中置入试剂的聚合物层或者是其中置入试剂的粘附层。
9.根据权利要求1至8任一项的组合物，其特征在于，所述其中置入试剂的聚合物层包含标准聚合物如聚酰胺、聚酰亚胺、聚四氟乙烯、聚乙烯、聚丙烯、聚氯乙烯、聚丙烯酸酯或聚甲基丙烯酸酯、聚苯乙烯或聚酯。
10.根据权利要求1至8任一项的组合物，其特征在于，所述其中置入试剂的粘附层包含基于天然或合成的橡胶、聚丙烯酸酯、聚酯、聚氯丁二烯、聚异丁烯、聚乙烯醚或聚脲的粘附剂，其优选与天然或合成的树脂和与氧化稳定剂相组合使用。
11.根据权利要求1至10任一项的组合物，其特征在于，作为纤维层包含由矿物纤维如玻璃、石棉、玄武岩，由动物纤维如丝或毛，由植物纤维如棉花或者由源自天然聚合物或合成聚合物的化学纤维构成的织物、针织物或无纺布，所述聚合物如聚酰胺、聚酰亚胺、聚四氟乙烯、聚乙烯、聚丙烯、聚氯乙烯、聚丙烯酸酯或聚甲基丙烯酸酯、聚苯乙烯或聚酯。
12.根据权利要求1至11任一项的组合物，其特征在于，包含保护层，其置于在其中置入试剂的层的相对于纤维层的另一侧表面上。
13.根据权利要求1至12任一项的组合物，其特征在于，作为保护层包含由塑料如聚乙烯、聚丙烯或聚酯构成的膜。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102009036485.4 | 2009-08-07 | ||
| DE200910036485 DE102009036485B4 (de) | 2009-08-07 | 2009-08-07 | Mittel zur zerstörenden Entsorgung von medizinischen Wirkstoffen in transdermalen therapeutischen Systemen |
| PCT/EP2010/004641 WO2011015308A2 (de) | 2009-08-07 | 2010-07-29 | Zerstörende entsorgung von medizinischen wirkstoffen in transdermalen therapeutischen systemen |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102596438A true CN102596438A (zh) | 2012-07-18 |
| CN102596438B CN102596438B (zh) | 2016-01-06 |
Family
ID=43416561
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201080034897.XA Active CN102596438B (zh) | 2009-08-07 | 2010-07-29 | 透皮治疗系统中药物活性物质的销毁性处理 |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US20120129415A1 (zh) |
| EP (1) | EP2461920B1 (zh) |
| JP (2) | JP5722323B2 (zh) |
| KR (1) | KR101726463B1 (zh) |
| CN (1) | CN102596438B (zh) |
| AU (1) | AU2010281089B2 (zh) |
| BR (1) | BR112012002763B8 (zh) |
| CA (1) | CA2770236C (zh) |
| DE (1) | DE102009036485B4 (zh) |
| ES (1) | ES2798256T3 (zh) |
| HK (1) | HK1172864A1 (zh) |
| IL (1) | IL217731A0 (zh) |
| MX (1) | MX2012001575A (zh) |
| RU (1) | RU2563131C2 (zh) |
| WO (1) | WO2011015308A2 (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108601748A (zh) * | 2016-01-20 | 2018-09-28 | Lts勒曼治疗系统股份公司 | 控制从形态稳定的含水组合物中的水释放 |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2019354562A1 (en) * | 2018-10-03 | 2021-03-18 | Safemedwaste, Inc. | Controlled medication denaturing composition and method |
| US10668312B2 (en) * | 2018-10-03 | 2020-06-02 | Okra Medical, Inc. | Controlled medication denaturing composition |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4510621A (en) * | 1983-06-30 | 1985-04-09 | Arvey Corporation | Self-sealing pouch for forming adhesive-to-adhesive seal |
| WO2003103673A1 (en) * | 2002-06-10 | 2003-12-18 | Purdue Pharma, L.P. | Disposal systems of transdermal delivery devices to prevent misuse of the active agents contained therein |
| WO2005041883A2 (en) * | 2003-10-28 | 2005-05-12 | Zars, Inc. | Reduction of unintended use of transdermal devices |
| US20050163717A1 (en) * | 2004-01-23 | 2005-07-28 | Birch Point Medical, Inc. | Abuse potential reduction in abusable substance dosage form |
| WO2007137732A2 (de) * | 2006-05-31 | 2007-12-06 | Lts Lohmann Therapie-Systeme Ag | Selbstzerstörendes transdermales therapeutisches system |
| WO2008024408A2 (en) * | 2006-08-22 | 2008-02-28 | Theraquest Biosciences, Inc. | Pharmaceutical formulations of cannabinoids for application to the skin and method of use |
| WO2008040512A2 (de) * | 2006-10-04 | 2008-04-10 | Grünenthal GmbH | Entsorgungssystem |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5236714A (en) | 1988-11-01 | 1993-08-17 | Alza Corporation | Abusable substance dosage form having reduced abuse potential |
| KR20050050615A (ko) * | 2002-04-23 | 2005-05-31 | 알자 코포레이션 | 남용될 가능성이 감소된 경피용 진통제 시스템 |
| DE10250084A1 (de) | 2002-10-25 | 2004-05-06 | Grünenthal GmbH | Gegen Missbrauch gesicherte Darreichungsform |
| US8790689B2 (en) * | 2003-04-30 | 2014-07-29 | Purdue Pharma L.P. | Tamper resistant transdermal dosage form |
| US7182955B2 (en) | 2003-04-30 | 2007-02-27 | 3M Innovative Properties Company | Abuse-resistant transdermal dosage form |
| US20070014839A1 (en) * | 2005-07-18 | 2007-01-18 | Stefan Bracht | Decomposer film for transdermal patches |
| DE102006035282A1 (de) * | 2006-07-31 | 2008-02-07 | Robert Bosch Gmbh | Verfahren zur Reduzierung des Moments einer Brennkraftmaschine |
| DE102008016804B4 (de) * | 2008-04-02 | 2012-01-05 | Lts Lohmann Therapie-Systeme Ag | Selbstzerstörendes transdermales therapeutisches System mit verbesserter Funktionalität und Wirksamkeit sowie seine Verwendung |
-
2009
- 2009-08-07 DE DE200910036485 patent/DE102009036485B4/de active Active
-
2010
- 2010-07-29 EP EP10744870.6A patent/EP2461920B1/de active Active
- 2010-07-29 AU AU2010281089A patent/AU2010281089B2/en not_active Ceased
- 2010-07-29 WO PCT/EP2010/004641 patent/WO2011015308A2/de active Application Filing
- 2010-07-29 MX MX2012001575A patent/MX2012001575A/es unknown
- 2010-07-29 CN CN201080034897.XA patent/CN102596438B/zh active Active
- 2010-07-29 RU RU2012108365/15A patent/RU2563131C2/ru not_active IP Right Cessation
- 2010-07-29 KR KR1020127005908A patent/KR101726463B1/ko active IP Right Grant
- 2010-07-29 ES ES10744870T patent/ES2798256T3/es active Active
- 2010-07-29 CA CA2770236A patent/CA2770236C/en active Active
- 2010-07-29 JP JP2012523229A patent/JP5722323B2/ja active Active
- 2010-07-29 US US13/388,829 patent/US20120129415A1/en active Pending
- 2010-07-29 BR BR112012002763A patent/BR112012002763B8/pt active IP Right Grant
-
2012
- 2012-01-25 IL IL217731A patent/IL217731A0/en unknown
- 2012-12-31 HK HK12113621.6A patent/HK1172864A1/zh unknown
-
2015
- 2015-03-24 JP JP2015060253A patent/JP6125556B2/ja active Active
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4510621A (en) * | 1983-06-30 | 1985-04-09 | Arvey Corporation | Self-sealing pouch for forming adhesive-to-adhesive seal |
| WO2003103673A1 (en) * | 2002-06-10 | 2003-12-18 | Purdue Pharma, L.P. | Disposal systems of transdermal delivery devices to prevent misuse of the active agents contained therein |
| WO2005041883A2 (en) * | 2003-10-28 | 2005-05-12 | Zars, Inc. | Reduction of unintended use of transdermal devices |
| WO2005041883A3 (en) * | 2003-10-28 | 2005-11-17 | Zars Inc | Reduction of unintended use of transdermal devices |
| US20050163717A1 (en) * | 2004-01-23 | 2005-07-28 | Birch Point Medical, Inc. | Abuse potential reduction in abusable substance dosage form |
| WO2007137732A2 (de) * | 2006-05-31 | 2007-12-06 | Lts Lohmann Therapie-Systeme Ag | Selbstzerstörendes transdermales therapeutisches system |
| WO2007137732A3 (de) * | 2006-05-31 | 2008-06-19 | Lohmann Therapie Syst Lts | Selbstzerstörendes transdermales therapeutisches system |
| WO2008024408A2 (en) * | 2006-08-22 | 2008-02-28 | Theraquest Biosciences, Inc. | Pharmaceutical formulations of cannabinoids for application to the skin and method of use |
| WO2008040512A2 (de) * | 2006-10-04 | 2008-04-10 | Grünenthal GmbH | Entsorgungssystem |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108601748A (zh) * | 2016-01-20 | 2018-09-28 | Lts勒曼治疗系统股份公司 | 控制从形态稳定的含水组合物中的水释放 |
Also Published As
| Publication number | Publication date |
|---|---|
| JP5722323B2 (ja) | 2015-05-20 |
| BR112012002763A2 (pt) | 2016-05-24 |
| KR20120059532A (ko) | 2012-06-08 |
| RU2012108365A (ru) | 2013-09-20 |
| HK1172864A1 (zh) | 2013-05-03 |
| WO2011015308A2 (de) | 2011-02-10 |
| CA2770236A1 (en) | 2011-02-10 |
| WO2011015308A3 (de) | 2012-05-03 |
| AU2010281089A1 (en) | 2012-03-01 |
| CA2770236C (en) | 2017-08-15 |
| JP2013501012A (ja) | 2013-01-10 |
| ES2798256T3 (es) | 2020-12-10 |
| MX2012001575A (es) | 2012-04-02 |
| CN102596438B (zh) | 2016-01-06 |
| AU2010281089B2 (en) | 2015-01-29 |
| KR101726463B1 (ko) | 2017-04-12 |
| IL217731A0 (en) | 2012-03-29 |
| DE102009036485A1 (de) | 2011-02-10 |
| EP2461920B1 (de) | 2020-04-29 |
| BR112012002763B1 (pt) | 2020-12-08 |
| RU2563131C2 (ru) | 2015-09-20 |
| BR112012002763B8 (pt) | 2021-07-27 |
| EP2461920A2 (de) | 2012-06-13 |
| DE102009036485B4 (de) | 2012-10-04 |
| US20120129415A1 (en) | 2012-05-24 |
| JP2015143251A (ja) | 2015-08-06 |
| JP6125556B2 (ja) | 2017-05-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Lee et al. | Dissolving microneedle patch for transdermal delivery of human growth hormone | |
| US6417227B1 (en) | Methods of delivery of cetyl myristoleate | |
| US8894621B2 (en) | Self-destructing transdermal therapeutic system having improved functionality and efficacy | |
| CN100409847C (zh) | 乌头属生物碱经皮给药系统 | |
| CN102596438A (zh) | 透皮治疗系统中药物活性物质的销毁性处理 | |
| CN101541315A (zh) | 抗真菌病用贴剂 | |
| CN107929268A (zh) | 一种含质子泵抑制剂药物的透皮贴剂及其制备方法 | |
| TWM586117U (zh) | 艾納香貼布 | |
| CN101856342A (zh) | 一种普伐他汀经皮给药制剂及其制备方法 | |
| CN101843602A (zh) | 贴剂和贴剂制剂 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1172864 Country of ref document: HK |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: GR Ref document number: 1172864 Country of ref document: HK |