WO2008040512A2 - Disposal system - Google Patents
Disposal system Download PDFInfo
- Publication number
- WO2008040512A2 WO2008040512A2 PCT/EP2007/008506 EP2007008506W WO2008040512A2 WO 2008040512 A2 WO2008040512 A2 WO 2008040512A2 EP 2007008506 W EP2007008506 W EP 2007008506W WO 2008040512 A2 WO2008040512 A2 WO 2008040512A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- disposal
- inactivation
- active substance
- drug delivery
- disposal system
- Prior art date
Links
- 239000013543 active substance Substances 0.000 claims abstract description 60
- 230000006378 damage Effects 0.000 claims abstract description 21
- 230000002779 inactivation Effects 0.000 claims description 74
- 239000010410 layer Substances 0.000 claims description 50
- 238000012377 drug delivery Methods 0.000 claims description 49
- -1 alkali metal salt Chemical class 0.000 claims description 36
- 229940079593 drug Drugs 0.000 claims description 30
- 239000003814 drug Substances 0.000 claims description 29
- 239000004480 active ingredient Substances 0.000 claims description 27
- 150000001875 compounds Chemical class 0.000 claims description 24
- 239000003795 chemical substances by application Substances 0.000 claims description 23
- 239000000853 adhesive Substances 0.000 claims description 17
- 230000001070 adhesive effect Effects 0.000 claims description 16
- 239000012790 adhesive layer Substances 0.000 claims description 16
- 239000011159 matrix material Substances 0.000 claims description 15
- 230000001681 protective effect Effects 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 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 claims description 11
- 229960001736 buprenorphine Drugs 0.000 claims description 11
- 150000002148 esters Chemical class 0.000 claims description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 230000000415 inactivating effect Effects 0.000 claims description 8
- 230000002265 prevention Effects 0.000 claims description 8
- 150000001408 amides Chemical class 0.000 claims description 7
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- DEXMFYZAHXMZNM-UHFFFAOYSA-N Narceine Chemical compound OC(=O)C1=C(OC)C(OC)=CC=C1C(=O)CC1=C(CCN(C)C)C=C(OCO2)C2=C1OC DEXMFYZAHXMZNM-UHFFFAOYSA-N 0.000 claims description 6
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 claims description 6
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 claims description 6
- 239000012528 membrane Substances 0.000 claims description 6
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound 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 claims description 6
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 239000011148 porous material Substances 0.000 claims description 5
- 229910052700 potassium Inorganic materials 0.000 claims description 5
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- 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 claims description 5
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 claims description 4
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 claims description 4
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- XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 claims description 4
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- WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 claims description 4
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- WTJBNMUWRKPFRS-UHFFFAOYSA-N hydroxypethidine Chemical compound C=1C=CC(O)=CC=1C1(C(=O)OCC)CCN(C)CC1 WTJBNMUWRKPFRS-UHFFFAOYSA-N 0.000 claims description 4
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- 229960000482 pethidine Drugs 0.000 claims description 4
- 239000011591 potassium Substances 0.000 claims description 4
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims description 4
- ZXWAUWBYASJEOE-UHFFFAOYSA-N proheptazine Chemical compound C=1C=CC=CC=1C1(OC(=O)CC)CCCN(C)CC1C ZXWAUWBYASJEOE-UHFFFAOYSA-N 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
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- YQYVFVRQLZMJKJ-JBBXEZCESA-N (+)-cyclazocine Chemical compound C([C@@]1(C)C2=CC(O)=CC=C2C[C@@H]2[C@@H]1C)CN2CC1CC1 YQYVFVRQLZMJKJ-JBBXEZCESA-N 0.000 claims description 3
- LGFMXOTUSSVQJV-NEYUFSEYSA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;(4r,4ar,7s,7ar,12bs)-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7,9-diol;1-[(3,4-dimethoxyphenyl)methyl]-6 Chemical compound Cl.Cl.Cl.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC.C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 LGFMXOTUSSVQJV-NEYUFSEYSA-N 0.000 claims description 3
- IYNWSQDZXMGGGI-NUEKZKHPSA-N 3-hydroxymorphinan Chemical compound C1CCC[C@H]2[C@H]3CC4=CC=C(O)C=C4[C@]21CCN3 IYNWSQDZXMGGGI-NUEKZKHPSA-N 0.000 claims description 3
- IJVCSMSMFSCRME-KBQPJGBKSA-N Dihydromorphine Chemical compound O([C@H]1[C@H](CC[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O IJVCSMSMFSCRME-KBQPJGBKSA-N 0.000 claims description 3
- OGDVEMNWJVYAJL-LEPYJNQMSA-N Ethyl morphine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OCC OGDVEMNWJVYAJL-LEPYJNQMSA-N 0.000 claims description 3
- OGDVEMNWJVYAJL-UHFFFAOYSA-N Ethylmorphine Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OCC OGDVEMNWJVYAJL-UHFFFAOYSA-N 0.000 claims description 3
- 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 claims description 3
- OZYUPQUCAUTOBP-QXAKKESOSA-N Levallorphan Chemical compound C([C@H]12)CCC[C@@]11CCN(CC=C)[C@@H]2CC2=CC=C(O)C=C21 OZYUPQUCAUTOBP-QXAKKESOSA-N 0.000 claims description 3
- JAQUASYNZVUNQP-USXIJHARSA-N Levorphanol Chemical compound C1C2=CC=C(O)C=C2[C@]23CCN(C)[C@H]1[C@@H]2CCCC3 JAQUASYNZVUNQP-USXIJHARSA-N 0.000 claims description 3
- UIQMVEYFGZJHCZ-SSTWWWIQSA-N Nalorphine Chemical compound C([C@@H](N(CC1)CC=C)[C@@H]2C=C[C@@H]3O)C4=CC=C(O)C5=C4[C@@]21[C@H]3O5 UIQMVEYFGZJHCZ-SSTWWWIQSA-N 0.000 claims description 3
- ONBWJWYUHXVEJS-ZTYRTETDSA-N Normorphine Chemical compound C([C@@H](NCC1)[C@@H]2C=C[C@@H]3O)C4=CC=C(O)C5=C4[C@@]21[C@H]3O5 ONBWJWYUHXVEJS-ZTYRTETDSA-N 0.000 claims description 3
- 239000008896 Opium Substances 0.000 claims description 3
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- 229960001349 alphaprodine Drugs 0.000 claims description 3
- UVAZQQHAVMNMHE-XJKSGUPXSA-N alphaprodine Chemical compound C=1C=CC=CC=1[C@@]1(OC(=O)CC)CCN(C)C[C@@H]1C UVAZQQHAVMNMHE-XJKSGUPXSA-N 0.000 claims description 3
- 229940035674 anesthetics Drugs 0.000 claims description 3
- 229960002512 anileridine Drugs 0.000 claims description 3
- LKYQLAWMNBFNJT-UHFFFAOYSA-N anileridine Chemical compound C1CC(C(=O)OCC)(C=2C=CC=CC=2)CCN1CCC1=CC=C(N)C=C1 LKYQLAWMNBFNJT-UHFFFAOYSA-N 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 3
- RDJGWRFTDZZXSM-RNWLQCGYSA-N benzylmorphine Chemical compound O([C@@H]1[C@]23CCN([C@H](C4)[C@@H]3C=C[C@@H]1O)C)C1=C2C4=CC=C1OCC1=CC=CC=C1 RDJGWRFTDZZXSM-RNWLQCGYSA-N 0.000 claims description 3
- FLKWNFFCSSJANB-UHFFFAOYSA-N bezitramide Chemical compound O=C1N(C(=O)CC)C2=CC=CC=C2N1C(CC1)CCN1CCC(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 FLKWNFFCSSJANB-UHFFFAOYSA-N 0.000 claims description 3
- 229960004611 bezitramide Drugs 0.000 claims description 3
- IFKLAQQSCNILHL-QHAWAJNXSA-N butorphanol Chemical compound N1([C@@H]2CC3=CC=C(C=C3[C@@]3([C@]2(CCCC3)O)CC1)O)CC1CCC1 IFKLAQQSCNILHL-QHAWAJNXSA-N 0.000 claims description 3
- 229960001113 butorphanol Drugs 0.000 claims description 3
- GPZLDQAEBHTMPG-UHFFFAOYSA-N clonitazene Chemical compound N=1C2=CC([N+]([O-])=O)=CC=C2N(CCN(CC)CC)C=1CC1=CC=C(Cl)C=C1 GPZLDQAEBHTMPG-UHFFFAOYSA-N 0.000 claims description 3
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- WDEFBBTXULIOBB-WBVHZDCISA-N dextilidine Chemical compound C=1C=CC=CC=1[C@@]1(C(=O)OCC)CCC=C[C@H]1N(C)C WDEFBBTXULIOBB-WBVHZDCISA-N 0.000 claims description 3
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- INUNXTSAACVKJS-OAQYLSRUSA-N dextromoramide Chemical compound C([C@@H](C)C(C(=O)N1CCCC1)(C=1C=CC=CC=1)C=1C=CC=CC=1)N1CCOCC1 INUNXTSAACVKJS-OAQYLSRUSA-N 0.000 claims description 3
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- RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 claims description 3
- RHUWRJWFHUKVED-UHFFFAOYSA-N dimenoxadol Chemical compound C=1C=CC=CC=1C(C(=O)OCCN(C)C)(OCC)C1=CC=CC=C1 RHUWRJWFHUKVED-UHFFFAOYSA-N 0.000 claims description 3
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- QIRAYNIFEOXSPW-UHFFFAOYSA-N dimepheptanol Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(O)CC)C1=CC=CC=C1 QIRAYNIFEOXSPW-UHFFFAOYSA-N 0.000 claims description 3
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- CANBGVXYBPOLRR-UHFFFAOYSA-N dimethylthiambutene Chemical compound C=1C=CSC=1C(=CC(C)N(C)C)C1=CC=CS1 CANBGVXYBPOLRR-UHFFFAOYSA-N 0.000 claims description 3
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- SVDHSZFEQYXRDC-UHFFFAOYSA-N dipipanone Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)CC)CC(C)N1CCCCC1 SVDHSZFEQYXRDC-UHFFFAOYSA-N 0.000 claims description 3
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- ZOWQTJXNFTWSCS-IAQYHMDHSA-N eptazocine Chemical compound C1N(C)CC[C@@]2(C)C3=CC(O)=CC=C3C[C@@H]1C2 ZOWQTJXNFTWSCS-IAQYHMDHSA-N 0.000 claims description 3
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- 229960001454 nitrazepam Drugs 0.000 description 1
- KJONHKAYOJNZEC-UHFFFAOYSA-N nitrazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1 KJONHKAYOJNZEC-UHFFFAOYSA-N 0.000 description 1
- 229960002640 nordazepam Drugs 0.000 description 1
- AKPLHCDWDRPJGD-UHFFFAOYSA-N nordazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)CN=C1C1=CC=CC=C1 AKPLHCDWDRPJGD-UHFFFAOYSA-N 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- GYGAZRPDUOHMAF-KHPPLWFESA-N oleyl acetate Chemical compound CCCCCCCC\C=C/CCCCCCCCOC(C)=O GYGAZRPDUOHMAF-KHPPLWFESA-N 0.000 description 1
- ADIMAYPTOBDMTL-UHFFFAOYSA-N oxazepam Chemical compound C12=CC(Cl)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1 ADIMAYPTOBDMTL-UHFFFAOYSA-N 0.000 description 1
- 229960004535 oxazepam Drugs 0.000 description 1
- VCCZBYPHZRWKFY-XIKOKIGWSA-N oxazolam Chemical compound C1([C@]23C4=CC(Cl)=CC=C4NC(=O)CN2C[C@H](O3)C)=CC=CC=C1 VCCZBYPHZRWKFY-XIKOKIGWSA-N 0.000 description 1
- 229950006124 oxazolam Drugs 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 229960003209 phenmetrazine Drugs 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- 229960003562 phentermine Drugs 0.000 description 1
- 229960002034 pinazepam Drugs 0.000 description 1
- MFZOSKPPVCIFMT-UHFFFAOYSA-N pinazepam Chemical compound C12=CC(Cl)=CC=C2N(CC#C)C(=O)CN=C1C1=CC=CC=C1 MFZOSKPPVCIFMT-UHFFFAOYSA-N 0.000 description 1
- 229960000753 pipradrol Drugs 0.000 description 1
- XSWHNYGMWWVAIE-UHFFFAOYSA-N pipradrol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(O)C1CCCCN1 XSWHNYGMWWVAIE-UHFFFAOYSA-N 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920001748 polybutylene Polymers 0.000 description 1
- 229920001721 polyimide Polymers 0.000 description 1
- 229920001195 polyisoprene Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- 150000003097 polyterpenes Chemical class 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920001289 polyvinyl ether Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 239000001508 potassium citrate Substances 0.000 description 1
- 229960002635 potassium citrate Drugs 0.000 description 1
- 235000011082 potassium citrates Nutrition 0.000 description 1
- 229960004856 prazepam Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 229950004859 profadol Drugs 0.000 description 1
- 229950010387 proheptazine Drugs 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 229960003394 remifentanil Drugs 0.000 description 1
- 229950008243 secbutabarbital Drugs 0.000 description 1
- KQPKPCNLIDLUMF-UHFFFAOYSA-N secobarbital Chemical compound CCCC(C)C1(CC=C)C(=O)NC(=O)NC1=O KQPKPCNLIDLUMF-UHFFFAOYSA-N 0.000 description 1
- 229960002060 secobarbital Drugs 0.000 description 1
- 230000021317 sensory perception Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000013464 silicone adhesive Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 229960003188 temazepam Drugs 0.000 description 1
- IQWYAQCHYZHJOS-UHFFFAOYSA-N tetrazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CCCCC1 IQWYAQCHYZHJOS-UHFFFAOYSA-N 0.000 description 1
- 229960005214 tetrazepam Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229940100640 transdermal system Drugs 0.000 description 1
- 229960003386 triazolam Drugs 0.000 description 1
- JOFWLTCLBGQGBO-UHFFFAOYSA-N triazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1Cl JOFWLTCLBGQGBO-UHFFFAOYSA-N 0.000 description 1
- KJIOQYGWTQBHNH-UHFFFAOYSA-N undecanol Chemical compound CCCCCCCCCCCO KJIOQYGWTQBHNH-UHFFFAOYSA-N 0.000 description 1
- 229960005392 vinylbital Drugs 0.000 description 1
- KGKJZEKQJQQOTD-UHFFFAOYSA-N vinylbital Chemical compound CCCC(C)C1(C=C)C(=O)NC(=O)NC1=O KGKJZEKQJQQOTD-UHFFFAOYSA-N 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
-
- 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
- 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
- A61K9/7061—Polyacrylates
-
- 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
Definitions
- the invention relates to a disposal system with controlled disposal comprising a drug delivery system to be disposed of containing an active substance with abuse potential and at least one of the disposable drug delivery system initially separated present, multi-layer disposal device for controlled destruction of the drug immediately after the first contact of the drug delivery system with the Entsorgungsmittei.
- unused pharmaceutical drug delivery systems such as drug-containing patches are usually disposed of with household waste or hospital garbage. However, these drug delivery systems may still contain large amounts of a pharmacologically active ingredient.
- US Patent US-B-5804215 a system for disposing of transdermal patches is described in US Patent US-B-5804215.
- This disposal is in one tear-resistant, foldable, planar disposal means, which has a larger surface area than the plaster to be disposed and is designed on one side with a sticky surface, including the patch to be disposed of.
- the drug is not destroyed with abuse potential, but only included, so that an effective, final protection against misuse of the amount of active substance still contained in the patch is not guaranteed.
- the patch containing an active substance with potential for abuse is enclosed in a disposal means which has an impermeable deposit for a compound suitable for inactivating the active substance. Only in an opening attempt to allow drug abuse this depot is mechanically destroyed, so that the inactivating compound released and inactivated after mixing with the active ingredient.
- This disposal system also has the disadvantage that the amount of active substance present in a transdermal system with abuse potential is not destroyed in a controlled manner after use or shelf life of the active substance delivery system, so that prevention of the abuse is not ensured.
- the known abuse prevention should be improved, according to the drug delivery system to be disposed containing an active substance with abuse potential only included in a disposal and uncontrolled without destruction of the drug with drug potential with the waste disposed of to prevent misuse, preferably preclude.
- the object of the present invention is encompassed by the provision of the disposal system according to the invention for the controlled abuse prevention of an active substance with abuse potential A) at least one to be disposed of, preferably sheet-like drug delivery system containing at least one drug with abuse potential
- Destruction according to the invention is the inactivation of the drug with abuse potential to at least one unsuitable for the abuser conversion, preferably the complete destruction or minimization of the concentration of the active ingredient, more preferably at least the chemical change of the drug to a stage in which no possibility of abuse more is, most preferably understood the complete destruction of the drug.
- the disposal system according to the invention preferably comprises a disposal means which is planar, wherein the effective area of the disposal means, d. H. the area which the inactivation system delivers is preferably at least as large as the area of the active substance-containing area of the active substance delivery system.
- the disposal means preferably has a layered structure comprising
- a cover layer impermeable to the inactivation system as a surface layer a layer, possibly adhesive, having the inactivation system and having a permeable layer, in which the inactivation system is distributed in a matrix material, taken up in a porous material or in a reservoir optionally having a membrane permeable to the inactivation system, is present,
- the permeable layer containing the inactivation system is preferably bonded on one of its surfaces to a capping layer impermeable to the inactivation system, its delivery is controlled only in one direction.
- the removable protective film preferably has release properties, so that a simple peeling is guaranteed.
- the permeable layer comprising the inactivation system is provided with a full-area adhesive layer permeable to the inactivation system, especially when the inactivation system is distributed in a matrix, or at least one adhesive edge around the reservoir containing the inactivation system around the corresponding porous portion of the layer.
- This reservoir is preferably chamber-shaped and may have at least two compartments separated from one another.
- the reservoir may be closed with a permeable membrane for the inactivation system or only with the removable protective film. Insofar as it is necessary for the destruction of the active ingredient by the inactivation system, by simple handling any separation between the compartments of the reservoir can be eliminated, so that the contents of the compartments can be brought together for mixing.
- the inactivation system can also be distributed in a matrix layer which is permeable to it, which may optionally also contain adhesives, so that the adhesive layer and this matrix layer produce a layer.
- the inactivating agent has an adhesive edge or an adhesive layer or is self-adhesive, it is preferably covered with a removable protective film before use.
- the inactivation system can be accommodated in a section of the layer which is permeable to the inactivation system and which is made of a porous, preferably flexible material whose areal extent is at least as large as the area of the active substance-containing area of the active substance delivery system to be disposed of.
- the porous material is an absorbent material, preferably having a sponge-like structure, from which the inactivation system, e.g. B. can already be released by light pressure
- absorbent material is understood as meaning materials which are capable of absorbing liquid or gel-like substances and, if appropriate, over a relatively long period of time, preferably 1-24 months, more preferably 1-12 months, even more preferably 1-8 months, most preferably 1-6 months, especially 1-4 months.
- absorbent materials sponges or absorbent textiles that are physiologically harmless may preferably be used. It is obvious to a person skilled in the art that, depending on the inactivation system used, absorbent materials with the corresponding necessary absorption capacity are used. This can be determined by simple preliminary tests.
- the inactivation system may be in solid, semi-solid or liquid form, preferably in solid or liquid form in the disposal means.
- the inactivation system may be distributed in the form of crystals, granules, pellets, lozenges, in powder form, in microcapsules, as a solution or as a gel in a matrix material, in a porous material, preferably a sponge, or in a reservoir.
- the inactivation system can be present in undissolved or in dissolved form. If the inactivation system is in dissolved form, it may preferably be contained in a porous, flexible material.
- the inactivation system is in dissolved form, it may preferably be provided with a viscosifier.
- the anti-drug efficacy of the inactivation system is physically, e.g. B. by dissolving in a suitable solvent, or chemically, for. B. by hydrolysis, to improve or only to produce.
- the inactivation system may preferably consist of at least two components which are mixed together only upon contact of the initially separately present inactivating agent with the drug delivery system.
- Such components may, for. B. a salt with the destructive action and a suitable solvent, particularly preferably water, be present initially in separate compartments of the reservoir of the disposal agent.
- a suitable solvent particularly preferably water
- the amounts or concentrations of the inactivation system are to be selected so that the destruction of the active substance begins immediately after contact of the disposal agent with the active substance delivery system and is completed within days, preferably within hours, without health risks if handled appropriately.
- the inactivation system comprises a compound which chemically destroys the active substance.
- a compound is preferably a compound selected from the group comprising inorganic or organic oxidizing agents, inorganic or organic reducing agents, the active substance with Abuse potential derivatizing compounds, acids, bases, organic salts and inorganic salts.
- the inactivation system comprises an alkali salt, preferably a sodium or potassium salt, preferably an oxidative acid or H 2 O 2 .
- the inactivation system comprises at least one compound selected from the group comprising sodium perborate, potassium perborate, sodium peroxide, benzoyl peroxide, carbamide peroxide, sodium percarbonate, potassium percarbonate, sodium persulfate, potassium persulfate, sodium peroxodisulfate, potassium peroxodisulfate, sodium perphosphate, potassium perphosphate, H 2 O 2 , peracetic acid and potassium permanganate.
- TAED tetraacetyl-ethylenediamine
- the drug delivery system of the disposal system according to the invention is preferably a sheet-like system for transdermal and / or topical drug delivery, preferably a patch.
- active ingredient delivery systems such as patches
- a controlled abuse-preventive disposal of used drug delivery systems, such as patches a controlled disposal of expired, unused patches is also possible.
- the drug delivery system to be disposed of is a used drug delivery system which still has a residual content of drug with abuse potential.
- the drug delivery system may be constructed according to the reservoir or matrix system.
- Bauer KH, Frömming K.-H., 5.3 C, Pharmazeutician Technologie, pp. 381-383; Müller RH, Hildebrand GE, Pharmaceutical Technology: Modern Dosage Forms, Chapter 8, are referenced. The corresponding description of the systems is considered part of the present disclosure.
- the drug delivery system may preferably comprise a carrier layer, an active agent-containing layer and an adhesive layer, wherein the active substance-containing layer may simultaneously be the adhesive layer in which the active ingredient is dissolved and / or dispersed in a matrix optionally together with the adhesive is present.
- Adhesives for the adhesive layer of the active substance delivery system are preferably pressure-sensitive adhesives, for example polymers such as polyacrylates, polyvinyl ethers, polyisobutylenes (PIB), styrene / isoprene or butadiene / styrene copolymers or polyisoprene rubbers.
- PIB polyisobutylenes
- silicone adhesives such as, for example, optionally crosslinked polydimethylsiloxanes.
- Also based on esters of glycines, glycerol or pentaerythrol, or hydrocarbons, such as polyterpenes are suitable.
- Acrylate-based adhesives are by polymerization of acrylates, methacrylates, alkylacrylates and or alkyl methacrylates, with optionally further ⁇ , ⁇ -unsaturated monomers, such as acrylamide, dimethylacrylamide, dimethylaminoethyl acrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, methoxyethyl acrylate, methoxyethyl methacrylate, acrylonitrile and / or vinyl acetate Fe can also be used for the production of the adhesive layer or an adhesive edge of the disposal agent described above.
- the carrier layer or covering layer of the active substance delivery system is preferably impermeable and inert for the substances contained in the active substance-containing layer and in the adhesive layer, in particular for the active substance, and may be based on polymers, such as polyesters, preferably polyethylene terephthalate, polyolefins, such as polyethylenes, polypropylenes or polybutylenes , Polycarbonates, polyethylene oxides, polyurethanes, polystyrroles, polyamides, polyimides, polyvinyl acetates, polyvinyl chlorides, polyvinylidene chlorides and / or copolymers such as acrylonitrile / butadiene / styrrole copolymers and / or mixtures thereof, optionally containing paper fibers or textile fibers, which may be metallized or pigmented if necessary.
- polymers such as polyesters, preferably polyethylene terephthalate, polyolefins, such as polyethylenes, poly
- the inactivation system impermeable cover layer of the above described disposal means may be identically constructed.
- the carrier layer or covering layer of the active substance delivery system or the inactivation system impermeable covering layer of the disposal agent may also consist of a combination of a metal foil and a polymer layer.
- the active ingredient-containing matrix layer of the active substance delivery system may contain matrix-forming polymers, skin penetration enhancers, solubilizers, crosslinkers, stabilizers, emulsifiers, preservatives, thickeners and / or further customary auxiliaries.
- the matrix-forming polymer used is preferably at least one film-forming polymer selected from the group comprising hydroxypropylcellulose, carboxymethylcellulose, polyethylenes, chlorinated polyethylenes, polypropylenes, polyurethanes, polycarbonates, polyacrylates, polyacrylates, polymethacrylates, polyvinyl alcohols, polyvinyl chlorides, polyvinylidene chlorides, polyvinylpyrrolidones, polyethylene terephthalates, polytetrafluoroethylenes, ethylene / propylene Copolymers, ethylene / ethyl acrylate copolymers, ethylene / vinyl acetate copolymers, ethylene / vinyl alcohol copolymers, ethylene / vinyl oxanol copolymers, vinyl chloride / vinyl acetate copolymers, vinyl pyrrolidone / ethylene / vinyl acetate copolymers, rubbers, rubbery, synthetic homo-, co- or block polymers, silicones,
- matrix-forming polymers and optionally adhesives can also be used for the preparation of the inactivation system-containing matrix layer of the above described disposal means.
- Antioxidants such as vitamin E, butylhydroxytoluene, butylated hydroxyanisole, ascorbic acid, ascorbyl palmitate, and / or chelating agents, such as, for example, can be used as stabilizers for the active substance-containing matrix or the active substance-containing reservoir of the active substance delivery system.
- B. Dinatriurnethylendiamintetraessigkladre, potassium or sodium citrate can be used.
- the active ingredient-containing matrix or the active substance-containing reservoir of the active substance delivery system may also contain conventional skin penetration enhancers.
- the drug delivery system may also include, in one or more layers, at least one plasticizer or skin permeation enhancer selected from the group consisting of long chain alcohols such as dodecanol, undecanol, octanol, esters of carboxylic acids with polyethoxylated alcohols, diesters of aliphatic dicarboxylic acids such as adipic acid, and caprylic acid medium chain triglycerides / or capric acid, coconut oil, polyhydric alcohols, such as 1, 2-propanediol, esters of polyhydric alcohols, such as glycerol with levulinic or caprylic, and etherified polyhydric alcohols.
- plasticizer or skin permeation enhancer selected from the group consisting of long chain alcohols such as dodecanol, undecanol, octanol, esters of carboxylic acids with polyethoxylated alcohols, diesters of aliphatic dicarboxylic acids such as adipic
- the peelable protective film of the drug delivery system or the disposal agent described above can be selected from polyethylene, polyester, polyethylene terephthalate, polypropylene, polysiloxane, polyvinyl chloride or polyurethane and optionally from treated paper fibers such.
- As cellophane and preferably have a silicone, fluorosilicone or fluorine-carbon coating as a release coating.
- Substances with abuse potential in particular those with a psychotropic effect, which are also suitable for transdermal and / or topical delivery, are known to the person skilled in the art.
- Many drugs with abuse potential especially those with psychotropic effect, have the property of being able to influence mental processes, i. they have a specific effect on mental functions. Such agents can thus affect mood, either whitening or cushioning.
- the active substances with potential for abuse are preferably active substances which, especially in the case of non-intended type of application, are accelerated in comparison with the intended topical or transdermal application Influencing the drug with the result desired by an abuser, namely the kick.
- This kick can z. B. can be achieved when the drug is extracted from the drug delivery system and then z. B. administered parenterally or orally.
- drugs with abuse potential in particular those drugs with psychotropic effect, which influence the human mind and / or sensory perception in a manner that they are in principle suitable for abuse with appropriate dosage, dosage form and Darreichungsart.
- the active substances with potential for abuse are especially active substances which have an effect on or via the nervous system according to the ATC index.
- These agents preferably include transdermally and / or topically administrable anesthetics [N01], analgesics [N02], antielectics [N03], antiparkinson agents [N04], psycholeptics [N05], psychoanaleptics [N06] and / or other nervous system agents [N07] , and corresponding stereoisomeric compounds, in each case their corresponding derivatives, physiologically acceptable enantiomers, stereoisomers, diastereomers and racemates and their physiologically acceptable derivatives, for example ethers, esters or amides, and in each case their physiologically acceptable compounds, in particular their salts and solvates, for example hydrochlorides.
- brackets correspond to the ATC index as used by the WHO for the classification of the drugs (preferred status: January 2005 or 2006).
- ATC index refers to U. Fricke, Anatomisch-Therapischchemische Klasstechnische with Paindosen: Official version of the ATC Index with DDD data for Germany in 2006, Scientific Institute of the AOK referenced.
- Derivatives in each case corresponding physiologically compatible enantiomers, stereoisomers, Diastereomers, racemates, in each case physiologically acceptable derivatives, such as ethers, esters or amides, and in each case physiologically acceptable compounds, in particular salts and solvates understood
- the substance to be disposed of according to the invention with abuse potential or psychotropic effect is at least one transdermally and / or topically administrable active ingredient selected from the group comprising alfentanil, allobarbital, allylprodin, alphaprodine, alprazolam, amfepramone, amfetamine, amfetaminil, amobarbital, anileridine , Apocodein, barbital, bemidone, benzylmorphine, bezitramide, bromazepam, Brotizolam, buprenorphine, butobarbital, butorphanol, camazepam, carfentanil, cathin / D-norpseudoephedrine, chlordiazepoxide, clobazam, clofedanol, clonazepam, clonitazene, clorazepate, clotiazepam, cloxazolam, ***e, codeine
- the active substance with abuse potential or psychotropic action to be disposed of according to the invention is particularly preferably at least one transdermally and / or topically administrable opioid selected from the group comprising allylprodin, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, Cyclazocine, desomorphine, dextromoramide, decocin, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, Eptazocine, ethoheptazine, ethorphine, ethylmethylthiambutene, ethylmorphine, etonitazene, fentanyl, heroin, hydrocodone, hydromorphone, hydroxypethidine
- the active ingredient according to the invention with abuse potential to at least one transdermally and / or topically administrable opioid selected from the group comprising buprenorphine, fentanyl and sufentanil, a corresponding stereoisomeric compound, a corresponding derivative, a physiologically acceptable enantiomer, stereoisomer , Diastereomeres, racemate, a physiologically acceptable derivative thereof, such as an ether, ester or amide, and in each case a physiologically acceptable compound, in particular a salt and solvate, for example hydrochloride.
- a transdermally and / or topically administrable opioid selected from the group comprising buprenorphine, fentanyl and sufentanil, a corresponding stereoisomeric compound, a corresponding derivative, a physiologically acceptable enantiomer, stereoisomer , Diastereomeres, racemate, a physiologically acceptable derivative thereof, such as an ether, ester or amide, and in each case a
- the active ingredient to be disposed of according to the invention with abuse potential or psychotropic effect is buprenorphine.
- Essential to the invention is that the controlled destruction of the drug with abuse potential is achieved only by applying the disposal agent on the drug-containing surface of the drug delivery system and begins immediately after the first contact of the drug delivery system with the disposal.
- the drug delivery system it is not necessary to include the drug delivery system to be disposed of in an inactivating agent, which still poses a risk of Abuse by the existing, not destroyed drug amount is given.
- the known inclusion of the drug delivery system to be disposed of without destruction of the active ingredient is avoided according to the invention, as by surface contact of the disposal agent with the active ingredient-containing region of the drug delivery system
- Another object of the invention therefore also relates to a method for the controlled disposal and controlled abuse prevention of a present in a drug delivery system to be disposed amount of an active substance with abuse potential, which is characterized in that to destroy the located in the drug-containing portion of the drug delivery system amount of an active ingredient multi-layer, inventive disposal means is applied and immediately after the application of the inactivating agent on the active substance-containing area destruction of the active ingredient is continued at least up to a completely unsuitable for abuse concentration of the active ingredient, preferably until complete destruction of the remaining amount of active ingredient.
- inventive disposal means is applied and immediately after the application of the inactivating agent on the active substance-containing area destruction of the active ingredient is continued at least up to a completely unsuitable for abuse concentration of the active ingredient, preferably until complete destruction of the remaining amount of active ingredient.
- the necessary duration of action of an inactivation system on the active ingredient or on the amount of active ingredient present can be determined by simple preliminary tests.
- Figure 1 shows a cross-section of the disposal means (C) comprising an inactivation system impermeable cover layer (1) having an adhesive layer (6) pervious to the inactivation system with a reservoir (2) containing an inactivation system (7).
- the reservoir (2) is closed by a membrane (8) permeable to the inactivation system.
- a protective film (3) impermeable to the inactivation system covers the adhesive layer.
- Figure 2 shows a cross section of the disposal means (C) with an inactivation system impermeable cover layer (1) and a matrix layer (5) containing and permeable to the inactivation system, covered with a protective film (3) impermeable to the inactivation system.
- Figure 3 shows a cross-section of the disposal means (C) comprising a capping layer (1) impermeable to the inactivation system and a porous sub-layer (9) containing the inactivation system, in which the inactivation system is incorporated.
- the porous sublayer (9) is bordered by an adhesive edge (10).
- the porous sub-layer (9) and the adhesive edge (10) are covered with a protective film (3) impermeable to the inactivation system.
- Figure 4 shows an embodiment of the disposal means (C) with a capping layer (1) impermeable to the inactivation system.
- the chamber-shaped reservoir (2) has two separate compartments (2a, 2b) and a membrane (8) permeable to the inactivation system.
- the compartments are separated by a wall (4) impermeable to the inactivation system, each containing one component (A or B) of the inactivation system.
- the membrane-shaped, permeable for the inactivation system layer is covered with a protective film (3).
- the partition (4) can be folded in the reservoir, whereby the two components A and B are mixed together, for. B. by dissolving a salt (A) in water (B) to an aqueous solution of the salt whereby the inactivation system is obtained.
- a cover layer a 420 mm wide, transparent polyester film is coated with the above-described mixture so that the weight per unit area of the dried adhesive layer is 80 g / m 2 .
- the solvents are removed by drying with heated air which is passed over the wet web.
- the heat treatment evaporates the solvents.
- the active ingredient-containing adhesive layer is covered with a 15 ⁇ m thick polyester film as a protective film, which can be removed again by silicone treatment. Using suitable cutting tools, a surface corresponding to the intended amount of active substance is punched out.
- a buprenorphine plaster produced according to a) is prepared in each case with a disposal agent according to the invention prepared according to b) (after detachment of the peelable protective film) for 2, 6 or 24 hours at 25 ° C.
- the residual content of buprenorphine in the patch is determined by conventional HPLC method.
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Abstract
The invention relates to a disposal system for the controlled disposal of an active substance with potential for misuse. Said system comprises at least one active substance dispensing system comprising an active substance with potential for misuse and at least one multilayer disposal means (C) which is separate from the active substance dispensing system and is used for the controlled destruction of the active substance directly after the active substance dispensing system has come into contact with the disposal means (C).
Description
Entsorgungssystem disposal system
Die Erfindung betrifft ein Entsorgungssystem mit kontrollierter Entsorgung umfassend ein zu entsorgendes Wirkstoffabgabesystem enthaltend einen Wirkstoff mit Missbrauchspotential und wenigstens ein von dem zu entsorgenden Wirkstoffabgabesystem zunächst separiert vorliegendes, mehrschichtiges Entsorgungsmittel zur kontrollierten Zerstörung des Wirkstoffs die unmittelbar nach dem ersten Kontakt des Wirkstoffabgabesystems mit dem Entsorgungsmittei einsetzt.The invention relates to a disposal system with controlled disposal comprising a drug delivery system to be disposed of containing an active substance with abuse potential and at least one of the disposable drug delivery system initially separated present, multi-layer disposal device for controlled destruction of the drug immediately after the first contact of the drug delivery system with the Entsorgungsmittei.
Gebrauchte oder abgelaufene, ungebrauchte pharmazeutische Wirkstoffabgabesysteme wie beispielsweise wirkstoffhaltige Pflaster werden üblicherweise durch den Hausmüll oder durch den Krankenhausmüll entsorgt. Diese Wirkstoffabgabesysteme können dabei aber noch große Mengen eines pharmakologischen, aktiven Wirkstoffes enthalten.Used or expired, unused pharmaceutical drug delivery systems such as drug-containing patches are usually disposed of with household waste or hospital garbage. However, these drug delivery systems may still contain large amounts of a pharmacologically active ingredient.
Dies stellt vor allem bei pharmazeutischen Wirkstoffen mit Missbrauchspotential, insbesondere solchen mit psychotroper Wirkung, wie beispielsweise Opioide, Stimulanzien, Tranquilizer etc. ein großes Problem dar. Diese Wirkstoffabgabesysteme können für einen Missbrauch dem Müll entnommen werden um daraus die noch vorhandene Wirkstoffmenge z. B. durch Extraktion zu gewinnen und anschließend zur Erzielung der gewünschten psychotropen Wirkung, nämlich eines sog. „Kicks", parenteral gespritzt oder oral eingenommen werden.This is a major problem, especially with pharmaceutical agents with abuse potential, especially those with psychotropic effect, such as opioids, stimulants, tranquilizers, etc. These drug delivery systems can be removed for misuse the garbage to the remaining amount of active ingredient z. B. by extraction and then to achieve the desired psychotropic effect, namely a so-called. "Kick", parenterally injected or taken orally.
Solche unzureichend entsorgten Wirkstoffabgabesysteme stellen daher eine nicht zu vernachlässigende Möglichkeit für einen intravenösen, oralen und/oder nasalen Missbrauch dar.Such inadequately disposed drug delivery systems therefore represent a non-negligible possibility for intravenous, oral and / or nasal abuse.
Nach dem Stand der Technik ist die Verhinderung eines solchen Missbrauchs durch eine ordnungsgemäße, kontrollierte Entsorgung eines Wirkstoffabgabesystems mit einem Wirkstoff mit Missbrauchspotential nicht gegeben.In the prior art, the prevention of such abuse by a proper, controlled disposal of a drug delivery system with a drug with abuse potential is not given.
So wird zum Beispiel ein System zur Entsorgung von transdermalen Pflastern in dem US Patent US-B-5804215 beschrieben. Bei dieser Entsorgung wird in einem
reißfesten, faltbaren, planaren Entsorgungsmittel, das eine größere Oberfläche als das zu entsorgende Pflaster aufweist und auf einer Seite mit einer klebrigen Oberfläche ausgestaltet ist, das zu entsorgende Pflaster eingeschlossen. Dabei wird der Wirkstoff mit Missbrauchspotential nicht zerstört, sondern nur eingeschlossen, so dass ein effektiver, endgültiger Schutz vor Missbrauch der in dem Pflaster noch enthaltenden Wirkstoffmenge nicht gewährleistet ist.For example, a system for disposing of transdermal patches is described in US Patent US-B-5804215. This disposal is in one tear-resistant, foldable, planar disposal means, which has a larger surface area than the plaster to be disposed and is designed on one side with a sticky surface, including the patch to be disposed of. In this case, the drug is not destroyed with abuse potential, but only included, so that an effective, final protection against misuse of the amount of active substance still contained in the patch is not guaranteed.
Weiterhin wird in WO02/085268 ein Entsorgungsmitte! für transdermale Systeme offenbart. Auch gemäß der Lehre dieser internationalen Anmeldung wird das Pflaster enthaltend einen Wirkstoff mit Missbrauchspotential in einem Entsorgungsmittel eingeschlossen, das ein für eine zur Inaktivierung des Wirkstoffes geeignete Verbindung undurchlässiges Depot aufweist. Erst bei einem Öffnungsversuch zur Ermöglichung eines Wirkstoffmissbrauchs wird dieses Depot mechanisch zerstört, so dass die Inaktivierungsverbindung freigesetzt und nach Vermischung mit dem Wirkstoff diesen inaktiviert.Furthermore, in WO02 / 085268 a disposal center! for transdermal systems. Also according to the teaching of this international application, the patch containing an active substance with potential for abuse is enclosed in a disposal means which has an impermeable deposit for a compound suitable for inactivating the active substance. Only in an opening attempt to allow drug abuse this depot is mechanically destroyed, so that the inactivating compound released and inactivated after mixing with the active ingredient.
Auch dieses Entsorgungssystem hat den Nachteil, dass die in einem transdermalen System vorhandener Wirkstoffmenge mit Missbrauchspotential nach Gebrauch bzw. Haltbarkeitsablauf des Wirkstoffabgabesystems bei der Entsorgung nicht kontrolliert zerstört wird, so dass eine Verhinderung des Missbrauchs nicht sichergestellt ist.This disposal system also has the disadvantage that the amount of active substance present in a transdermal system with abuse potential is not destroyed in a controlled manner after use or shelf life of the active substance delivery system, so that prevention of the abuse is not ensured.
Aufgabe der vorliegenden Erfindung war es daher, ein einfaches Entsorgungssystem zur kontrollierten Missbrauchsverhinderung einer in einem zu entsorgenden Wirkstoffabgabesystem (noch) vorhandenen Menge eines Wirkstoffes mit Missbrauchspotential zur Verfügung zu stellen. Insbesondere sollte die bekannte Missbrauchsverhinderung verbessert werden, gemäß der zu entsorgendes Wirkstoffabgabesystem enthaltend einen Wirkstoff mit Missbrauchspotential nur in einem Entsorgungsmittel eingeschlossen und ohne Zerstörung des Wirkstoffes mit Wirkstoffpotential mit dem Müll unkontrolliert entsorgt wird, um einen Missbrauch zu erschweren, vorzugsweise auszuschließen.It was therefore an object of the present invention to provide a simple disposal system for the controlled prevention of abuse of an amount of an active substance with abuse potential (still) present in a drug delivery system to be disposed of. In particular, the known abuse prevention should be improved, according to the drug delivery system to be disposed containing an active substance with abuse potential only included in a disposal and uncontrolled without destruction of the drug with drug potential with the waste disposed of to prevent misuse, preferably preclude.
Die Aufgabe der vorliegenden Erfindung wird durch das Zurverfügungsstellen des erfindungsgemäßen Entsorgungssystems zur kontrollierten Missbrauchsverhinderung eines Wirkstoffes mit Missbrauchspotential umfassend
A) wenigstens ein zu entsorgendes, vorzugsweise flächenförmiges Wirkstoffabgabesystem enthaltend wenigstens einen Wirkstoff mit MissbrauchspotentialThe object of the present invention is encompassed by the provision of the disposal system according to the invention for the controlled abuse prevention of an active substance with abuse potential A) at least one to be disposed of, preferably sheet-like drug delivery system containing at least one drug with abuse potential
undand
B) wenigstens ein von dem zu entsorgenden Wirkstoffabgabesystem zunächst separiert vorliegendes, mehrschichtiges, vorzugsweise flächenförmiges Entsorgungsmittel mit einem Inaktivierungssystem zur kontrollierten, unmittelbar nach dem Inkontaktbringen des zu entsorgenden Wirkstoffabgabesystems mit dem Entsorgungsmittel einsetzenden Zerstörung der in dem zu entsorgenden Wirkstoffabgabesystem vorhandenen Menge des Wirkstoffes mit MissbrauchspotentialB) at least one of the disposable drug delivery system initially separated present, multi-layer, preferably sheet disposal means with an inactivation system for controlled, immediately after contacting the to be disposed drug delivery system with the disposal destructive destruction of existing in the drug delivery system to be disposed amount of the drug with abuse potential
gelöst.solved.
Unter Zerstörung wird erfindungsgemäß die Inaktivierung des Wirkstoffes mit Missbrauchspotential bis zumindest einer für den Missbraucher ungeeignete Umwandlung, vorzugsweise die völlige Vernichtung bzw. Minimierung der Konzentration des Wirkstoffes, besonders bevorzugt zumindest die chemische Veränderung des Wirkstoffes bis zu einer Stufe, bei der keine Missbrauchsmöglichkeit mehr gegeben ist, ganz besonders bevorzugt die völlige Vernichtung des Wirkstoffes verstanden.Destruction according to the invention is the inactivation of the drug with abuse potential to at least one unsuitable for the abuser conversion, preferably the complete destruction or minimization of the concentration of the active ingredient, more preferably at least the chemical change of the drug to a stage in which no possibility of abuse more is, most preferably understood the complete destruction of the drug.
Das erfindungsgemäße Entsorgungssystem umfasst vorzugsweise ein Entsorgungsmittel, das flächenförmig ist, wobei die wirksame Fläche des Entsorgungsmittels, d. h. die Fläche, die das Inaktivierungssystem abgibt, vorzugsweise wenigstens so groß ist, wie die Fläche des wirkstoffhaltigen Bereichs des Wirkstoffabgabesystems.The disposal system according to the invention preferably comprises a disposal means which is planar, wherein the effective area of the disposal means, d. H. the area which the inactivation system delivers is preferably at least as large as the area of the active substance-containing area of the active substance delivery system.
Das Entsorgungsmittel weist vorzugsweise einen schichtförmigen Aufbau, umfassendThe disposal means preferably has a layered structure comprising
- eine für das Inaktivierungssystem undurchlässige Deckschicht als Oberflächenschicht,
- eine vorzugsweise an die Deckschicht angrenzende, ggf. klebefähige, das Inaktivierungssystem aufweisende und dafür durchlässige Schicht, in der das Inaktivierungssystem in einem Matrixmaterial verteilt, in einem porösen Material aufgenommen oder in einem Reservoir, das ggf. eine für das Inaktivierungssystem durchlässige Membran aufweist, vorliegt,a cover layer impermeable to the inactivation system as a surface layer, a layer, possibly adhesive, having the inactivation system and having a permeable layer, in which the inactivation system is distributed in a matrix material, taken up in a porous material or in a reservoir optionally having a membrane permeable to the inactivation system, is present,
- gegebenenfalls eine für das Inaktivierungssystem durchlässige Klebeschicht,optionally an adhesive layer permeable to the inactivation system,
- oder gegebenenfalls wenigstens einen Kleberand, und- or optionally at least one adhesive edge, and
- eine für das Inaktivierungssystem undurchlässige, ablösbare Schutzfolie auf.- A removable for the inactivation system, removable protective film.
Da die das Inaktivierungssystem enthaltende und dafür durchlässige Schicht vorzugsweise auf einer ihrer Oberflächen mit einer für das Inaktivierungssystem undurchlässigen Deckschicht verbunden ist, wird dessen Abgabe nur in eine Richtung gesteuert.Since the permeable layer containing the inactivation system is preferably bonded on one of its surfaces to a capping layer impermeable to the inactivation system, its delivery is controlled only in one direction.
Die ablösbare Schutzfolie weist vorzugsweise Release-Eigenschaften auf, damit ein einfaches Abziehen gewährleistet ist.The removable protective film preferably has release properties, so that a simple peeling is guaranteed.
In einer bevorzugten Ausführungsform ist die das Inaktivierungssystem aufweisende und dafür durchlässigen Schicht mit einer für das Inaktivierungssystem durchlässigen, vollflächigen Klebeschicht versehen, insbesondere dann, wenn das Inaktivierungssystem in einer Matrix verteilt vorliegt, oder sie weist zumindest einen Kleberand um das, das Inaktivierungssystem enthaltende Reservoir oder um den entsprechenden porösen Teilbereich der Schicht auf.In a preferred embodiment, the permeable layer comprising the inactivation system is provided with a full-area adhesive layer permeable to the inactivation system, especially when the inactivation system is distributed in a matrix, or at least one adhesive edge around the reservoir containing the inactivation system around the corresponding porous portion of the layer.
Dieses Reservoir ist vorzugsweise kammerförmig und kann wenigstens zwei Abteilungen aufweisen, die voneinander getrennt sind. Das Reservoir kann mit einer für das Inaktivierungssystem durchlässigen Membran oder nur mit der ablösbaren Schutzfolie verschlossen sein. Sofern es für die Zerstörung des Wirkstoffes durch das Inaktivierungssystem notwendig ist, kann durch einfache Handhabung eine ggf. vorhandene Abtrennung zwischen den Abteilungen des Reservoirs beseitigt werden, so dass die Inhalte der Abteilungen zur Vermischung zusammengebracht werden können.
Das Inaktivierungssystem kann auch in einer dafür durchlässigen Matrixschicht verteilt vorliegen, die gegebenenfalls auch Klebestoffe enthalten kann so dass die Klebeschicht und diese Matrixschicht eine Schicht ergeben.This reservoir is preferably chamber-shaped and may have at least two compartments separated from one another. The reservoir may be closed with a permeable membrane for the inactivation system or only with the removable protective film. Insofar as it is necessary for the destruction of the active ingredient by the inactivation system, by simple handling any separation between the compartments of the reservoir can be eliminated, so that the contents of the compartments can be brought together for mixing. The inactivation system can also be distributed in a matrix layer which is permeable to it, which may optionally also contain adhesives, so that the adhesive layer and this matrix layer produce a layer.
Sofern das Inaktivierungsmittel einen Kleberand oder eine Klebeschicht aufweist oder selbst klebefähig ist, ist diese(r) vor dem Gebrauch vorzugsweise mit einer ablösbaren Schutzfolie abgedeckt.If the inactivating agent has an adhesive edge or an adhesive layer or is self-adhesive, it is preferably covered with a removable protective film before use.
Ferner kann das Inaktivierungssystem in einem aus einem porösen, vorzugsweise flexiblen Material bestehenden Teilbereich der für das Inaktivierungssystem durchlässigen Schicht aufgenommen sein, dessen flächenförmige Ausdehnung wenigstens so groß ist wie die Fläche des wirkstoffhaltigen Bereichs des zu entsorgenden Wirkstoffabgabesystems. Bevorzugt handelt es sich bei dem porösen Material um ein saugfähiges Material, vorzugsweise mit einer schwammartige Struktur, aus der das Inaktivierungssystem, z. B. schon durch leichten Druck, abgegeben werden kannFurthermore, the inactivation system can be accommodated in a section of the layer which is permeable to the inactivation system and which is made of a porous, preferably flexible material whose areal extent is at least as large as the area of the active substance-containing area of the active substance delivery system to be disposed of. Preferably, the porous material is an absorbent material, preferably having a sponge-like structure, from which the inactivation system, e.g. B. can already be released by light pressure
Unter saugfähigem Material im Sinne der vorliegenden Erfindung werden Materialen verstanden, welche in der Lage sind, flüssige oder gelartige Stoffe aufzunehmen und ggf. über einen längeren Zeitraum, vorzugsweise 1-24 Monate, bevorzugter 1-12 Monate, noch bevorzugter 1-8 Monate, am bevorzugtesten 1-6 Monate, insbesondere 1-4 Monate zu speichern. Als Beispiele für saugfähige Materialen können vorzugsweise Schwämme oder saugfähigen Textilien, die physiologisch unbedenklich sind, verwendet werden. Für einen Fachmann ist selbstverständlich, dass je nach verwendetem Inaktivierungssystem saugfähige Materialien mit der entsprechend notwendigen Aufnahmekapazität verwendet werden. Dies kann durch einfache Vorversuche ermittelt werden.For the purposes of the present invention, "absorbent material" is understood as meaning materials which are capable of absorbing liquid or gel-like substances and, if appropriate, over a relatively long period of time, preferably 1-24 months, more preferably 1-12 months, even more preferably 1-8 months, most preferably 1-6 months, especially 1-4 months. As examples of absorbent materials, sponges or absorbent textiles that are physiologically harmless may preferably be used. It is obvious to a person skilled in the art that, depending on the inactivation system used, absorbent materials with the corresponding necessary absorption capacity are used. This can be determined by simple preliminary tests.
Das Inaktivierungssystem kann in fester, halbfester oder flüssiger Form, bevorzugt in fester oder flüssiger Form im Entsorgungsmittel vorliegen. Erfindungsgemäß kann das Inaktivierungssystem in Form von Kristallen, Granulaten, Pellets, Pastillen, in Pulverform, in Mikrokapseln, als Lösung oder als Gel in einem Matrixmaterial verteilt, in einem porösen Material, vorzugsweise einem Schwamm aufgenommen, oder in einem Reservoir vorliegen.
Erfindungsgemäß kann das Inaktivierungssystem in ungelöster oder in gelöster Form vorliegen. Liegt das Inaktivierungssystem in gelöster Form vor, kann es vorzugsweise in einem porösen, flexiblen Material aufgenommen sein.The inactivation system may be in solid, semi-solid or liquid form, preferably in solid or liquid form in the disposal means. In accordance with the invention, the inactivation system may be distributed in the form of crystals, granules, pellets, lozenges, in powder form, in microcapsules, as a solution or as a gel in a matrix material, in a porous material, preferably a sponge, or in a reservoir. According to the invention, the inactivation system can be present in undissolved or in dissolved form. If the inactivation system is in dissolved form, it may preferably be contained in a porous, flexible material.
Sofern das Inaktivierungssystem in gelöster Form vorliegt, kann es vorzugsweise mit einem Viskositätserhöhenden Mittel ausgerüstet sein.If the inactivation system is in dissolved form, it may preferably be provided with a viscosifier.
Es ist auch möglich, die gegen den Wirkstoff gerichtete Wirksamkeit des Inaktivierungssystem, insbesondere wenn es in einem Reservoir vorliegt, physikalisch, z. B. durch Auflösen in einem geeigneten Lösungsmittel, oder chemisch, z. B. durch Hydrolyse, zu verbessern bzw. erst zu erzeugen. Dazu kann das Inaktivierungssystem vorzugsweise aus wenigstens zwei Komponenten bestehen, die erst beim Kontakt des zunächst separat vorliegenden Inaktivierungsmittels mit dem Wirkstoffabgabesystem miteinander vermischt werden.It is also possible that the anti-drug efficacy of the inactivation system, especially if present in a reservoir, is physically, e.g. B. by dissolving in a suitable solvent, or chemically, for. B. by hydrolysis, to improve or only to produce. For this purpose, the inactivation system may preferably consist of at least two components which are mixed together only upon contact of the initially separately present inactivating agent with the drug delivery system.
Solche Komponenten können z. B. ein Salz mit der Zerstörungswirkung und ein geeignetes Lösungsmittel, besonders bevorzugt Wasser, sein, die zunächst in getrennten Abteilungen des Reservoirs des Entsorgungsmittels vorliegen. Durch Zusammenbringen dieser beiden Komponenten erhält man das die Zerstörung des Wirkstoffes bewirkende Inaktivierungssystem, indem nämlich das Salz in dem Lösungsmittel aufgelöst wird, wodurch eine rasche Wirksamkeit zur Zerstörung des Wirkstoffes erzielt wird.Such components may, for. B. a salt with the destructive action and a suitable solvent, particularly preferably water, be present initially in separate compartments of the reservoir of the disposal agent. By bringing together these two components, one obtains the inactivation system which causes the destruction of the active ingredient, namely, by dissolving the salt in the solvent, whereby a rapid activity for destroying the active ingredient is achieved.
Durch einfachen Druck auf das Reservoir können z. B. die Abteilungen eines Reservoirs verbunden und eine zerstörende Salzlösung zur Diffusion durch eine dafür durchlässige Membran des Reservoirs hergestellt werden.By simple pressure on the reservoir z. B. the departments of a reservoir connected and a destructive saline solution for diffusion through a permeable membrane of the reservoir are made.
Die Mengen bzw. Konzentrationen des Inaktivierungssystems sind erfindungsgemäß so zu wählen, dass die Zerstörung des Wirkstoffes unmittelbar nach Kontakt des Entsorgungsmittels mit dem Wirkstoffabgabesystem beginnt und innerhalb von Tagen, vorzugsweise innerhalb von Stunden ohne gesundheitliche Risiken bei sachgemäßer Handhabung abgeschlossen wird.According to the invention, the amounts or concentrations of the inactivation system are to be selected so that the destruction of the active substance begins immediately after contact of the disposal agent with the active substance delivery system and is completed within days, preferably within hours, without health risks if handled appropriately.
Vorzugsweise umfasst das Inaktivierungssystem eine den Wirkstoff chemisch zerstörende Verbindung. Eine solche Verbindung ist vorzugsweise eine Verbindung ausgewählt aus der Gruppe umfassend anorganische oder organische Oxidationsmittel, anorganische oder organische Reduktionsmittel, den Wirkstoff mit
Missbrauchspotential derivatisierende Verbindungen, Säuren, Basen, organische Salze und anorganische Salze.Preferably, the inactivation system comprises a compound which chemically destroys the active substance. Such a compound is preferably a compound selected from the group comprising inorganic or organic oxidizing agents, inorganic or organic reducing agents, the active substance with Abuse potential derivatizing compounds, acids, bases, organic salts and inorganic salts.
Entsprechend erfolgt die Zerstörung des Wirkstoffs mit Missbrauchspotential durch oxydative, reduktive, alkalische, saure oder hydrolytische Einwirkung.Accordingly, the destruction of the drug with abuse potential by oxidative, reductive, alkaline, acid or hydrolytic action takes place.
In einer bevorzugten Ausführungsform umfasst das Inaktivierungssystem ein Alkalisalz, vorzugsweise ein Natrium- oder Kaliumsalz, vorzugsweise von einer Säure mit oxydativer Wirkung oder von H2O2.In a preferred embodiment, the inactivation system comprises an alkali salt, preferably a sodium or potassium salt, preferably an oxidative acid or H 2 O 2 .
Besonders bevorzugt umfasst das Inaktivierungssystem wenigstens eine Verbindung ausgewählt aus der Gruppe umfassend Natriumperborat, Kaliumperborat, Natriumperoxid, Benzoylperoxid, Carbamidperoxid, Natriumpercarbonat, Kaliumpercarbonat, Natriumpersulfat, Kaliumpersulfat, Natriumperoxidisulfat, Kaliumperoxidisulfat, Natriumperphosphat, Kaliumperphosphat, H2O2, Peressigsäure und Kaliumpermanganat.More preferably, the inactivation system comprises at least one compound selected from the group comprising sodium perborate, potassium perborate, sodium peroxide, benzoyl peroxide, carbamide peroxide, sodium percarbonate, potassium percarbonate, sodium persulfate, potassium persulfate, sodium peroxodisulfate, potassium peroxodisulfate, sodium perphosphate, potassium perphosphate, H 2 O 2 , peracetic acid and potassium permanganate.
Diese Verbindungen können in eine wässrige Lösung übergeführt werden oder liegen bereits als eine solche vor. Um bei Raumtemperatur die volle zerstörende Wirkung zu entfalten, können die genannten Inaktivierungssysteme auch einen Aktivator wie z. B. TAED (Tetraacetyl-ethylendiamin) umfassen.These compounds can be converted into an aqueous solution or are already present as such. In order to develop the full destructive effect at room temperature, said inactivation systems can also be an activator such. As TAED (tetraacetyl-ethylenediamine) include.
Das Wirkstoffabgabesystem des erfindungsgemäßen Entsorgungssystems ist vorzugsweise ein flächenförmiges System zur transdermalen und/oder topischen Wirkstoffabgabe, vorzugsweise ein Pflaster. Es ist dem Fachmann bekannt, dass Wirkstoffabgabesysteme, wie Pflaster, nach ihrer vorgegebenen Gebrauchsdauer noch bis zu 80 Gew.% der ursprünglichen Wirkstoffmenge enthalten können, so dass sich das Entsorgungsmittel als ein Element des erfindungsgemäßen Entsorgungssystems ganz besonders gut zur Zerstörung von (Rest-)Mengen eines Wirkstoffes mit Missbrauchspotential eignet. Neben einer kontrollierten missbrauchsverhindemden Entsorgung von gebrauchten Wirkstoffabgabesystemen, wie Pflastern, ist auch eine kontrollierte Entsorgung von abgelaufenen, unbenutzten Pflastern möglich. Bevorzugt handelt es sich bei dem zu entsorgenden Wirkstoffabgabesystem um ein gebrauchtes Wirkstoffabgabesystem, das noch einen Restgehalt an Wirkstoff mit Missbrauchspotential aufweist.
Das Wirkstoffabgabesystem kann nach dem Reservoir- oder Matrix- System aufgebaut sein. In diesem Zusammenhang kann auf Bauer K. H., Frömming K.-H., Führer C, Pharmazeutische Technologie, Seiten 381-383; Müller R. H., Hildebrand G. E., Pharmazeutische Technologie: Moderne Arzneiformen, Kapitel 8, verwiesen werden. Die entsprechende Beschreibung der Systeme gilt als Teil der vorliegenden Offenbarung.The drug delivery system of the disposal system according to the invention is preferably a sheet-like system for transdermal and / or topical drug delivery, preferably a patch. It is known to the person skilled in the art that active ingredient delivery systems, such as patches, may still contain up to 80% by weight of the original amount of active ingredient after their predetermined period of use, so that the disposal agent, as an element of the disposal system according to the invention, is particularly well suited for the destruction of (residual) Amounts of an active substance with abuse potential is suitable. In addition to a controlled abuse-preventive disposal of used drug delivery systems, such as patches, a controlled disposal of expired, unused patches is also possible. Preferably, the drug delivery system to be disposed of is a used drug delivery system which still has a residual content of drug with abuse potential. The drug delivery system may be constructed according to the reservoir or matrix system. In this connection, Bauer KH, Frömming K.-H., Führer C, Pharmazeutische Technologie, pp. 381-383; Müller RH, Hildebrand GE, Pharmaceutical Technology: Modern Dosage Forms, Chapter 8, are referenced. The corresponding description of the systems is considered part of the present disclosure.
Gemäß dem Matrix-System kann das Wirkstoffabgabesystem vorzugsweise eine Trägerschicht bzw. Deckschicht, eine wirkstoffhaltige Schicht und eine Klebeschicht aufweisen, wobei die wirkstoffhaltige Schicht gleichzeitig die Klebeschicht sein kann, in dem der Wirkstoff gelöst und/oder dispergiert in einer Matrix gegebenenfalls zusammen mit dem Klebstoff vorliegt.According to the matrix system, the drug delivery system may preferably comprise a carrier layer, an active agent-containing layer and an adhesive layer, wherein the active substance-containing layer may simultaneously be the adhesive layer in which the active ingredient is dissolved and / or dispersed in a matrix optionally together with the adhesive is present.
Als Klebstoffe für die Klebeschicht des Wirkstoffabgabesystems werden vorzugsweise druckempfindliche Klebstoffe („pressure-sensitive adhesives") eingesetzt. Beispielsweise eignen sich dafür Polymere wie Polyacrylate, Polyvinylether, Polyisobutylene (PIB), Styrol/Isopren- oder Butadien-/Styrol Copolymere oder Polyisopren Kautschuke. Weiterhin eignen sich Silikon-Klebstoffe, wie z. B. gegebenenfalls vernetzte Polydimethylsiloxane. Ferner sind Kunststoffe auf Basis von Ester von Glycinen, Glycerin oder Pentaerythrol, oder Kohlenwasserstoffen, wie Polyterpene geeignet. Klebstoffe auf Acrylatbasis werden durch Polymerisation von Acrylaten, Methacrylaten, Alkylacrylaten und/oder Alkylmethacrylaten, mit gegebenenfalls weiteren α, ß- ungesättigten Monomeren, wie Acrylamid, Dimethylacrylamid, Dimethylaminoethylacrylat, Hydroxyethylacrylat, Hydroxypropylacrylat, Methoxyethylacrylat, Methoxyethylmethacrylat, Acrylnitril und/oder Vinylacetat, hergestellt. Diese vorstehend genannten Klebstoffe können auch zur Herstellung der Klebeschicht bzw. eines Kleberandes des vorstehend beschriebenen Entsorgungsmittels eingesetzt werden.Adhesives for the adhesive layer of the active substance delivery system are preferably pressure-sensitive adhesives, for example polymers such as polyacrylates, polyvinyl ethers, polyisobutylenes (PIB), styrene / isoprene or butadiene / styrene copolymers or polyisoprene rubbers. Also suitable are silicone adhesives, such as, for example, optionally crosslinked polydimethylsiloxanes.Also based on esters of glycines, glycerol or pentaerythrol, or hydrocarbons, such as polyterpenes are suitable.Acrylate-based adhesives are by polymerization of acrylates, methacrylates, alkylacrylates and or alkyl methacrylates, with optionally further α, β-unsaturated monomers, such as acrylamide, dimethylacrylamide, dimethylaminoethyl acrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, methoxyethyl acrylate, methoxyethyl methacrylate, acrylonitrile and / or vinyl acetate Fe can also be used for the production of the adhesive layer or an adhesive edge of the disposal agent described above.
Die Trägerschicht bzw. Deckschicht des Wirkstoffabgabesystems ist vorzugsweise für die in der wirkstoffhaltigen Schicht und in der Klebeschicht enthaltenen Stoffen, insbesonders für den Wirkstoff, undurchlässig und inert, und kann auf Polymeren, wie Polyester, vorzugsweise Polyethylenterephthalat, Polyolefinen, wie Polyethylenen, Polypropylenen oder Polybutylenen, Polycarbonaten, Polyethylenoxiden, Polyurethanen, Polystyrrolen, Polyamiden, Polyimiden, Polyvinylacetaten, Polyvinylchloriden, Polyvinylidenchloriden und/oder Copolymeren
wie Acrylonitril/Butadien/Styrrol Copolymeren und/oder deren Mischungen, gegebenenfalls enthaltend Papierfasern oder Textilfasern basieren, die bei Bedarf metallisiert oder pigmentiert sein können.The carrier layer or covering layer of the active substance delivery system is preferably impermeable and inert for the substances contained in the active substance-containing layer and in the adhesive layer, in particular for the active substance, and may be based on polymers, such as polyesters, preferably polyethylene terephthalate, polyolefins, such as polyethylenes, polypropylenes or polybutylenes , Polycarbonates, polyethylene oxides, polyurethanes, polystyrroles, polyamides, polyimides, polyvinyl acetates, polyvinyl chlorides, polyvinylidene chlorides and / or copolymers such as acrylonitrile / butadiene / styrrole copolymers and / or mixtures thereof, optionally containing paper fibers or textile fibers, which may be metallized or pigmented if necessary.
Die für das Inaktivierungssystem undurchlässige Deckschicht des vorstehend beschriebenen Entsorgungsmittels kann identisch aufgebaut sein. Die Trägerschicht bzw. Deckschicht des Wirkstoffabgabesystems bzw. die für das Inaktivierungssystem undurchlässige Deckschicht des Entsorgungsmittels kann auch aus einer Kombination aus einer Metallfolie und einer Polymerschicht bestehen.The inactivation system impermeable cover layer of the above described disposal means may be identically constructed. The carrier layer or covering layer of the active substance delivery system or the inactivation system impermeable covering layer of the disposal agent may also consist of a combination of a metal foil and a polymer layer.
Die wirkstoffhaltige Matrix-Schicht des Wirkstoffabgabesystems kann matrixbildende Polymere, Hautdurchdringungsverstärker, Lösungsvermittler, Vernetzer, Stabilisatoren, Emulgatoren, Konservierungsmittel, Verdickungsmittel und/oder weitere übliche Hilfsmittel enthalten.The active ingredient-containing matrix layer of the active substance delivery system may contain matrix-forming polymers, skin penetration enhancers, solubilizers, crosslinkers, stabilizers, emulsifiers, preservatives, thickeners and / or further customary auxiliaries.
Als matrixbildendes Polymeres wird vorzugsweise wenigstens ein filmbildendes Polymeres ausgewählt aus der Gruppe umfassend Hydroxypropylcellulose, Carboxymethylcellulose, Polyethylene, chlorierte Polyethylene, Polypropylene, Polyurethane, Polycarbonate, Polyacrylsäureester, Polyacrylate, Polymethacrylate, Polyvinylalkohole, Polyvinylchloride, Polyvinylidenchloride, Polyvinylpyrrolidone, Polyethylenterephthalate, Polytetrafluoroethylene, Ethylen/Propylen Copolymere, Ethylen/Ethylacrylat Copolymere, Ethylen/Vinylacetat Copolymere, Ethylen/Vinylalkohol Copolymere, Ethylen/Vinyloxyethanol Copolymere, Vinylchlorid/Vinylacetat Copolymere, Vinylpyrrolidon/Ethylen/Vinylacetat Copolymere, Kautschuke, gummiartige, synthetische Homo-, Co- oder Blockpolymere, Silikone, Silikon-Derivate, vorzugsweise Siloxan/Methacrylat Copolymere, Cellulose-Derivate, vorzugsweise Ethylcellulose oder Celluloseether und deren Mischungen eingesetzt. Wenn die wirkstoffhaltige Schicht gleichzeitig die Klebeschicht ist, enthält sie vorzugsweise neben wenigstens einem der aufgezählten Polymeren zumindest einen der vorstehend aufgeführten Klebstoffe.The matrix-forming polymer used is preferably at least one film-forming polymer selected from the group comprising hydroxypropylcellulose, carboxymethylcellulose, polyethylenes, chlorinated polyethylenes, polypropylenes, polyurethanes, polycarbonates, polyacrylates, polyacrylates, polymethacrylates, polyvinyl alcohols, polyvinyl chlorides, polyvinylidene chlorides, polyvinylpyrrolidones, polyethylene terephthalates, polytetrafluoroethylenes, ethylene / propylene Copolymers, ethylene / ethyl acrylate copolymers, ethylene / vinyl acetate copolymers, ethylene / vinyl alcohol copolymers, ethylene / vinyl oxanol copolymers, vinyl chloride / vinyl acetate copolymers, vinyl pyrrolidone / ethylene / vinyl acetate copolymers, rubbers, rubbery, synthetic homo-, co- or block polymers, silicones, silicone Derivatives, preferably siloxane / methacrylate copolymers, cellulose derivatives, preferably ethylcellulose or cellulose ethers and mixtures thereof. If the active substance-containing layer is at the same time the adhesive layer, it preferably contains, in addition to at least one of the enumerated polymers, at least one of the above-mentioned adhesives.
Diese matrixbildenden Polymere und gegebenenfalls Klebstoffe können auch für die Herstellung der das Inaktivierungssystem enthaltenden Matrixschicht des vorstehend beschriebenen Entsorgungsmittels verwendet werden.
Als Stabilisatoren für die wirkstoffhaltige Matrix bzw. das wirkstoffhaltige Reservoir des Wirkstoffabgabesystems können Antioxidantien, wie Vitamin E, Butylhydroxytoluol, Butylhydroxyanisol, Ascorbinsäure, Ascorbylpalmitat, und/oder Chelatbildner, wie z. B. Dinatriurnethylendiamintetraessigsäure, Kalium- oder Natriumeitrat verwendet werden.These matrix-forming polymers and optionally adhesives can also be used for the preparation of the inactivation system-containing matrix layer of the above described disposal means. Antioxidants such as vitamin E, butylhydroxytoluene, butylated hydroxyanisole, ascorbic acid, ascorbyl palmitate, and / or chelating agents, such as, for example, can be used as stabilizers for the active substance-containing matrix or the active substance-containing reservoir of the active substance delivery system. B. Dinatriurnethylendiamintetraessigsäure, potassium or sodium citrate can be used.
Die wirkstoffhaltige Matrix bzw. das wirkstoffhaltige Reservoir des Wirkstoffabgabesystems kann auch übliche Hautdurchdringungsverstärker enthalten.The active ingredient-containing matrix or the active substance-containing reservoir of the active substance delivery system may also contain conventional skin penetration enhancers.
Das Wirkstoffabgabesystem kann auch in einer oder mehreren Schichten wenigstens einen Weichmacher oder Hautdurchdringungsverstärker ausgewählt aus der Gruppe umfassend langkettige Alkohole, wie Dodecanol, Undecanol, Octanol, Ester von Carbonsäuren mit polyethoxylierten Alkoholen, Diester von aliphatischen Dicarbonsäuren, wie Adipinsäure, und mittelkettige Triglyceride von Caprylsäure und/oder Caprinsäure, Kokosfett, mehrwertige Alkohole, wie 1 ,2-Propandiol, Ester von mehrwertigen Alkoholen, wie Glycerin mit Lävulinsäure oder Caprylsäure, und veretherte mehrwertige Alkohole enthalten.The drug delivery system may also include, in one or more layers, at least one plasticizer or skin permeation enhancer selected from the group consisting of long chain alcohols such as dodecanol, undecanol, octanol, esters of carboxylic acids with polyethoxylated alcohols, diesters of aliphatic dicarboxylic acids such as adipic acid, and caprylic acid medium chain triglycerides / or capric acid, coconut oil, polyhydric alcohols, such as 1, 2-propanediol, esters of polyhydric alcohols, such as glycerol with levulinic or caprylic, and etherified polyhydric alcohols.
Die ablösbare Schutzfolie des Wirkstoffabgabesystems bzw. des vorstehend beschriebenen Entsorgungsmittels kann aus Polyethylen, Polyester, Polyethylenterephthalat, Polypropylen, Polysiloxan, Polyvinylchlorid oder Polyurethan und gegebenenfalls aus behandelten Papierfasern, wie z. B. Zellophan, bestehen und vorzugsweise eine Silikon-, Fluorsilikon- oder Fluor-Kohlenstoffbeschichtung als Release-Beschichtung aufweisen.The peelable protective film of the drug delivery system or the disposal agent described above can be selected from polyethylene, polyester, polyethylene terephthalate, polypropylene, polysiloxane, polyvinyl chloride or polyurethane and optionally from treated paper fibers such. As cellophane, and preferably have a silicone, fluorosilicone or fluorine-carbon coating as a release coating.
Wirkstoffe mit Missbrauchspotential, insbesondere solche mit psychotroper Wirkung, die auch zur transdermalen und/oder topischen Abgabe geeignet sind, sind dem Fachmann bekannt. Viele Wirkstoffe mit Missbrauchspotential, insbesondere solche mit psychotroper Wirkung, besitzen die Eigenschaft psychische Prozesse beeinflussen zu können, d.h. sie besitzen eine spezifische Wirkung auf psychische Funktionen. Solche Wirkstoffe können somit die Stimmung beeinflussen, entweder aufhellend oder dämpfend.Substances with abuse potential, in particular those with a psychotropic effect, which are also suitable for transdermal and / or topical delivery, are known to the person skilled in the art. Many drugs with abuse potential, especially those with psychotropic effect, have the property of being able to influence mental processes, i. they have a specific effect on mental functions. Such agents can thus affect mood, either whitening or cushioning.
Bevorzugt handelt es sich bei den Wirkstoffen mit Missbrauchspotential, insbesondere solchen mit psychotroper Wirkung, um Wirkstoffe, die vor allem bei nicht bestimmungsgemäßer Art der Anwendung ein gegenüber der bestimmungsgemäßen topischen bzw. transdermalen Applikation beschleunigtes
Anfluten des Wirkstoffes mit dem von einem Missbraucher gewünschten Ergebnis bewirken, nämlich den Kick. Dieser Kick kann z. B. erreicht werden, wenn der Wirkstoff aus dem Wirkstoffabgabesystem extrahiert und anschließend z. B. parenteral oder oral verabreicht wird. Im Sinne der Erfindung sind unter Wirkstoffen mit Missbrauchspotential, insbesondere solche Wirkstoffe mit psychotroper Wirkung zu verstehen, welche bei entsprechender Dosierung, Darreichungsform und Darreichungsart die menschliche Verstandestätigkeit und/oder Sinneswahrnehmung in einer Weise beeinflussen, dass sie grundsätzlich zu einem Missbrauch geeignet sind.The active substances with potential for abuse, in particular those with a psychotropic effect, are preferably active substances which, especially in the case of non-intended type of application, are accelerated in comparison with the intended topical or transdermal application Influencing the drug with the result desired by an abuser, namely the kick. This kick can z. B. can be achieved when the drug is extracted from the drug delivery system and then z. B. administered parenterally or orally. For the purposes of the invention are to be understood by drugs with abuse potential, in particular those drugs with psychotropic effect, which influence the human mind and / or sensory perception in a manner that they are in principle suitable for abuse with appropriate dosage, dosage form and Darreichungsart.
Dabei handelt es sich bei den Wirkstoffen mit Missbrauchspotential, insbesondere bei solchen mit psychotroper Wirkung, besonders um Wirkstoffe, die nach dem ATC- Index eine Wirkung auf bzw. über das Nervensystem ausüben. Diese Wirkstoffe umfassen vorzugsweise transdermal und/oder topisch verabreichbare Anästhetika [N01], Analgetika [N02], Antieleptika [N03], Antiparkinsonmittel [N04], Psycholeptika [N05], Psychoanaleptika [N06] und/oder andere Mittel für das Nervensystem [N07], sowie entsprechende stereoisomere Verbindungen, jeweils deren entsprechende Derivate, physiologisch verträglichen Enantiomere, Stereoisomere, Diastereomere und Racemate und deren physiologisch verträglichen Derivate, beispielsweise Ether, Ester oder Amide, und jeweils deren physiologisch verträgliche Verbindungen, insbesondere deren Salze und Solvate, beispielsweise Hydrochloride. Die in eckigen Klammern angegebenen Bezeichnungen entsprechen dabei dem ATC-Index, wie er von der WHO zur Klassifizierung der Arzneistoffe verwendet wird (bevorzugter Stand: Januar 2005 oder 2006). Hinsichtlich weiterer Einzelheiten zum ATC-Index wird beispielsweise verwiesen werden auf U. Fricke, Anatomisch-therapeutischchemische Klassifikation mit Tagesdosen: Amtliche Fassung des ATC-Index mit DDD-Angaben für Deutschland im Jahre 2006, Wissenschaftliches Institut der AOK verwiesen.The active substances with potential for abuse, in particular those with a psychotropic effect, are especially active substances which have an effect on or via the nervous system according to the ATC index. These agents preferably include transdermally and / or topically administrable anesthetics [N01], analgesics [N02], antielectics [N03], antiparkinson agents [N04], psycholeptics [N05], psychoanaleptics [N06] and / or other nervous system agents [N07] , and corresponding stereoisomeric compounds, in each case their corresponding derivatives, physiologically acceptable enantiomers, stereoisomers, diastereomers and racemates and their physiologically acceptable derivatives, for example ethers, esters or amides, and in each case their physiologically acceptable compounds, in particular their salts and solvates, for example hydrochlorides. The designations in brackets correspond to the ATC index as used by the WHO for the classification of the drugs (preferred status: January 2005 or 2006). For further details on the ATC index, reference may be made, for example, to U. Fricke, Anatomisch-Therapischchemische Klassifikation with Tagesdosen: Official version of the ATC Index with DDD data for Germany in 2006, Scientific Institute of the AOK referenced.
Von den oben genannten Wirkstoffen mit Missbrauchspotential, insbesondere solche mit psychotroper Wirkung, wird im Sinne der vorliegenden Erfindung vorzugsweise wenigstens ein Wirkstoff ausgewählt aus der Gruppe umfassend Opioide, Stimulanzien, Tranquilizer (Barbiturate und Benzodiazepine), weitere Betäubungsmittel, jeweils entsprechende stereoisomere Verbindungen, jeweils entsprechende Derivate, jeweils entsprechende physiologisch verträgliche Enantiomere, Stereoisomere,
Diastereomere, Racemate, jeweils davon physiologisch verträgliche Derivate, wie beispielsweise Ether, Ester oder Amide, und jeweils physiologisch verträgliche Verbindungen, insbesondere Salze und Solvate, verstandenFor the purposes of the present invention, at least one active substance selected from the group consisting of opioids, stimulants, tranquilizers (barbiturates and benzodiazepines), further anesthetics, in each case corresponding stereoisomeric compounds, in each case corresponding to the abovementioned active substances with abuse potential, in particular those having a psychotropic effect Derivatives, in each case corresponding physiologically compatible enantiomers, stereoisomers, Diastereomers, racemates, in each case physiologically acceptable derivatives, such as ethers, esters or amides, and in each case physiologically acceptable compounds, in particular salts and solvates understood
Insbesondere handelt es sich bei dem erfindungsgemäß zu entsorgenden Wirkstoff mit Missbrauchspotential bzw. psychotroper Wirkung um wenigstens einen transdermal und/oder topisch verabreichbaren Wirkstoff ausgewählt aus der Gruppe umfassend Alfentanil, Allobarbital, Allylprodin, Alphaprodin, Alprazolam, Amfepramon, Amfetamin, Amfetaminil, Amobarbital, Anileridin, Apocodein, Barbital, Bemidon, Benzylmorphin, Bezitramid, Bromazepam, Brotizolam, Buprenorphin, Butobarbital, Butorphanol, Camazepam, Carfentanil, Cathin / D-Norpseudoephedrin, Chlordiazepoxid, Clobazam, Clofedanol, Clonazepam, Clonitazen, Clorazepat, Clotiazepam, Cloxazolam, Cocain, Codein, Cyclazocin, Cyclobarbital, Cyclorphan, Cyprenorphin, Delorazepam, Desomorphin, Dextromoramid, Dextropropoxyphen, Dezocin, Diamorphon, Diampromid, Diazepam, Dihydrocodein, Dihydromorphin, Dihydromorphon, Dimenoxadol, Dimepheptanol, Dimethylthiambuten, Dioxaphetylbutyrat, Dipipanon, Dronabinol, Eptazocin, Estazolam, Ethoheptazin, Ethorphin, Ethylloflazepat, Ethylmethylthiambuten, Ethylmorphin, Etonitazen, Etorphin, Fencamfamin, Fenetyllin, Fenpipramid, Fenproporex, Fentanyl, Fludiazepam, Flunitrazepam, Flurazepam, Halazepam, Haloxazolam, Heroin, Hydrocodon, Hydromorphon, Hydroxymethyl-morphinan, Hydroxypethidin, Isomethadon, Ketazolam, Ketobemidon, Levacetylmethadol (LAAM), Levallorphan, Levomethadon, Levophenacylmorphan, Levorphanol, Levoxemacin, Lofentanil, Loprazolam, Lorazepam, Lormetazepam, Mazindol, Medazepam, Mefenorex, Meperidin, Meprobamat, Meptazinol, Metamfetamin, Metapon, Metazocin, Methadon, Methadon, Methaqualon, 3-Methylfentanyl, 4-Methylfentanyl, Methylmorphin, Methylphenidat, Methylphenobarbital, Methyprylon, Metopon, Midazolam, Modafinil, Morphin, Myrophin, N-(1-Methyl-2-piperidinoethyl)-N-(2-pyridyl)propionamid, Nabilon, Nalbuphen, Nalbuphin, Nalorphin, Narcein, Nicomorphin, Nimetazepam, Nitrazepam, Nordazepam, Norlevorphanol, Normethadon, Normorphin, Norpipanon, Opium, Oxazepam, Oxazolam, Oxycodon, Oxymorphon, Papaver somniferum, Papaveretum, Pentazocin, Pentobarbital, Pernolin, Pethidin, Phenadoxon, Phenazocin, Phenmetrazin, Phenobarbital, Phenomorphan, Phenoperidin, Phentermin, Pholcodein, Piminodin, Pinazepam, Pipradrol, Piritramid, Prazepam, Profadol, Proheptazin, Promedol, Properidin, Properidin, Propheptazin, Propiram,
Propoxyphen, Remifentanil, Secbutabarbital, Secobarbital, Sufentanil, Temazepam, Tetrazepam, Tilidin (eis und trans), Tramadol, Triazolam, Vinylbital, (1 R1 2R)-3-(2- Dimethylaminomethyl-cyclohexyl)-phenol, (1 R, 2R, 4S)-2- (Dimethylamino)methyl-4- (p-fluorbenzyloxy)-1-(m-methoxyphenyl)cyclohexanol, (1 RS1 3RS, 6RS)-6- Dimethylaminomethyl-1-(3-methoxy-phenyl)-cyclohexan-1 , (1S, 2S)-3(3- Dimethylamino-1 -ethyl-2-methyl-propyl)-phenol, (2R, 3R)-1 -Dimethylamino-3(3- Methoxy-phenyl)-2-methyl-pentan-3-ol, (1 R, 2R)-3-(3-Dimethylamino-1-ethyl-2- methyi-propyi)-phenoi, (RR-SS)-2', 4'-Difiuoro-3-hydroxy-biρheny!-4-carbonsäure 3- (2-dimethylaminomethyl-1-hydroxy-cyclohexyl)-phenyl, ( RR-SS )-2-Acetoxy-4- trifluoromethyl-benzoesäure 3-(2-dimethylamino-methyl-1-hydroxy-cyclohexyl)-phenyl ester, (RR-SS)-2-Hydroxy-4-methoxy-benzoesäure 3-(2-dimethylaminomethyl-1 - hydroxy-cyclohexyl)-phenyl-ester, (RR-SS)-2-Hydroxy-4-methyl-benzoesäure 3-(2- dimethylaminomethyl-1 -hydroxy-cyclohexyl)-phenyl ester, (RR-SS)-2-Hydroxy-4- trifluoromethyl-benzoesäure 3-(2-dimethylaminomethyl-1-hydroxy-cyclohexyl)-phenyl ester, (RR-SS)-2-Hydroxy-5-nitro-benzoesäure 3-(2-dimethylaminomethyl-1 -hydroxy- cyclohexyl)-phenyl ester, (RR-SS)-4-Chloro-2-hydroxy-benzoesäure 3-(2- dimethylaminomethyl-1-hydroxy-cyclohexyl)-phenyl ester, 3-(2- Dimethylamino-methyl-1-hydroxy-cyclohexyl)phenyl 2-(6-methoxy-naphthalen-2-yl)- propionat, 3-(2-Dimethylaminomethyl-cyclohex-1 -enyl)-phenyl 2-(4-isobutyl-phenyl)- propionat, 3-(2-Dimethylaminomethyl-cyclohex-1 -enyl)-phenyl 2-(6-methoxy- naphthalen-2-yl)-propionat, 3-diol, vorzugsweise als Racemat und 3-(2- Dimethylaminomethyl-1-hydroxy-cyclohexyl)-phenyl 2-(4-isobutyl-phenyl)-propionat, sowie entsprechende stereoisomere Verbindungen, jeweils deren entsprechende Derivate, physiologisch verträglichen Enantiomere, Stereoisomere, Diastereomere und Racemate und deren physiologisch verträglichen Derivate, beispielsweise Ether, Ester oder Amide, und jeweils deren physiologisch verträgliche Verbindungen, insbesondere deren Salze und Solvate, beispielsweise Hydrochloride.In particular, the substance to be disposed of according to the invention with abuse potential or psychotropic effect is at least one transdermally and / or topically administrable active ingredient selected from the group comprising alfentanil, allobarbital, allylprodin, alphaprodine, alprazolam, amfepramone, amfetamine, amfetaminil, amobarbital, anileridine , Apocodein, barbital, bemidone, benzylmorphine, bezitramide, bromazepam, Brotizolam, buprenorphine, butobarbital, butorphanol, camazepam, carfentanil, cathin / D-norpseudoephedrine, chlordiazepoxide, clobazam, clofedanol, clonazepam, clonitazene, clorazepate, clotiazepam, cloxazolam, ***e, codeine , Cyclazocine, cyclobarbital, cyclorphan, cyprenorphine, delorazepam, desomorphine, dextromoramide, dextropropoxyphene, decocin, diamorphone, diampromide, diazepam, dihydrocodeine, dihydromorphine, dihydromorphone, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, dronabinol, eptazocine, estazolam, ethoheptazine, ethorphine , Ethyllaborate, ethylmethylthiambutene, ethylmorphine, etonitazene, etorphine, fencamfamine, fenetylline, fenpipramide, fenproporex, fentanyl, fludiazepam, flunitrazepam, flurazepam, halazepam, haloxazolam, heroin, hydrocodone, hydromorphone, hydroxymethylmorphinan, hydroxypethidine, isomethadone, ketazolam, ketobemidone, levacetylmethadol (LAAM), levallorphan, levomethadone, levophenacylmorphan, levorphanol, levoxemacin, lofentanil, loprazolam, lorazepam, lormetazepam, mazindol, medazepam, mefenorex, meperidine, meprobamate, meptazinol, metamfetamine, metapon, metazocin, methadone, methadone, methaqualone, 3-methylfentanyl, 4-methylfentanyl, methylmorphine, methylphenidate, methylphenobarbital, methyprylon, metopon, midazolam, modafinil, morphine, myrophin, N- (1-methyl-2-piperidinoethyl) -N- (2-pyridyl) -propionamide, nabilone, nalbuphene, nalbuphine, nalorphine , Narcein, nicomorphine, nimetazepam, nitrazepam, nordazepam, norlevorphanol, normethadone, normorphine, norpipanone, opium, oxazepam, oxazolam, oxycodone, O. xymorphone, papaver somniferum, papaveretum, pentazocine, pentobarbital, pernoline, pethidine, phenadoxone, phenazocine, phenmetrazine, phenobarbital, phenomorphan, phenoperidine, phentermine, pholcodein, piminodine, pinazepam, pipradrol, piritramide, prazepam, profadol, proheptazine, promedol, propperidine, propperidine , Propheptazine, Propiram, Propoxyphene, remifentanil, secbutabarbital, secobarbital, sufentanil, temazepam, tetrazepam, tilidine (eis and trans), tramadol, triazolam, vinylbital, (1R 1 2R) -3- (2-dimethylaminomethylcyclohexyl) phenol, (1R, 2R, 4S) -2- (dimethylamino) methyl-4- (p-fluorobenzyloxy) -1- (m-methoxyphenyl) cyclohexanol, (1RS 1 3RS, 6RS) -6-dimethylaminomethyl-1- (3-methoxy-phenyl ) -cyclohexane-1, (1S, 2S) -3 (3-dimethylamino-1-ethyl-2-methyl-propyl) -phenol, (2R, 3R) -1-dimethylamino-3 (3-methoxy-phenyl) - 2-methyl-pentan-3-ol, (1R, 2R) -3- (3-dimethylamino-1-ethyl-2-methyl-2-propyl) -phenoxy, (RR-SS) -2 ', 4'-difluoro 3-hydroxy-bi-phenyl-4-carboxylic acid 3- (2-dimethylaminomethyl-1-hydroxy-cyclohexyl) -phenyl, (RR-SS) -2-acetoxy-4-trifluoromethyl-benzoic acid 3- (2-dimethylamino-methyl 1-hydroxy-cyclohexyl) -phenyl ester, (RR-SS) -2-hydroxy-4-methoxybenzoic acid 3- (2-dimethylaminomethyl-1-hydroxy-cyclohexyl) -phenyl-ester, (RR-SS) - 2-hydroxy-4-methyl-benzoic acid 3- (2-dimethylaminomethyl-1-hydroxycyclohexyl) -phenyl l ester, (RR-SS) -2-hydroxy-4-trifluoromethyl-benzoic acid 3- (2-dimethylaminomethyl-1-hydroxy-cyclohexyl) -phenyl ester, (RR-SS) -2-hydroxy-5-nitro-benzoic acid 3- (2-dimethylaminomethyl-1-hydroxycyclohexyl) phenyl ester, (RR-SS) -4-chloro-2-hydroxybenzoic acid 3- (2-dimethylaminomethyl-1-hydroxy-cyclohexyl) -phenyl ester, 3 - (2-Dimethylamino-methyl-1-hydroxycyclohexyl) phenyl 2- (6-methoxynaphthalene-2-yl) propionate, 3- (2-dimethylaminomethylcyclohex-1-enyl) -phenyl 2- (4 -isobutyl-phenyl) propionate, 3- (2-dimethylaminomethyl-cyclohex-1-enyl) -phenyl 2- (6-methoxynaphthalene-2-yl) -propionate, 3-diol, preferably as racemate and 3- ( 2-dimethylaminomethyl-1-hydroxy-cyclohexyl) -phenyl 2- (4-isobutyl-phenyl) -propionate, and corresponding stereoisomeric compounds, in each case their corresponding derivatives, physiologically acceptable enantiomers, stereoisomers, diastereomers and racemates and their physiologically tolerated derivatives, for example Ethers, esters or amides, and each of their p physiologically compatible compounds, in particular their salts and solvates, for example hydrochlorides.
Besonders bevorzugt handelt es sich bei dem erfindungsgemäß zu entsorgenden Wirkstoff mit Missbrauchspotential bzw. psychotroper Wirkung um wenigstens ein transdermal und/oder topisch verabreichbares Opioid ausgewählt aus der Gruppe umfassend Allylprodin, Alphaprodin, Anileridin, Benzylmorphin, Bezitramid, Buprenorphin, Butorphanol, Clonitazen, Codein, Cyclazocin, Desomorphin, Dextromoramid, Dezocin, Diampromid, Dihydrocodein, Dihydromorphin, Dimenoxadol, Dimepheptanol, Dimethylthiambuten, Dioxaphetyl butyrat, Dipipanon,
Eptazocin, Ethoheptazin, Ethorphin, Ethylmethylthiambuten, Ethylmoφhin, Etonitazen, Fentanyl, Heroin, Hydrocodon, Hydromorphon, Hydroxypethidin, Isomethadon, Ketobemidon, Levallorphan, Levorphanol, Levophenacylmorphan, Lofentanil, Meperidin, Meptazinol, Metazocin, Methadon, Metopon, Morphin, Myrophin, Nalbuphin, Narcein, Nicomorphin, Norlevorphanol, Normethadon, Nalorphin, Normorphin, Norpipanon, Opium, Oxycodon, Oxymorphon, Papaveretum, Pentazocin, Phenadoxon, Phenomorphan, Phenazocin, Phenoperidin, Piminodin, Piriiramid, Propheptazin, Promedoi, Properidin, Propiram, Propoxyphen, Sufentanil, Tramadol und Tilidin, eine entsprechende stereoisomere Verbindung, ein entsprechendes Derivat, ein physiologisch verträgliches Enantiomeres, Stereoisomeres, Diastereomeres, Racemat, ein davon physiologisch verträgliches Derivat, wie beispielsweise Ether, Ester oder Amid, und jeweils eine physiologisch verträgliche Verbindung, insbesondere ein Salz und Solvat.The active substance with abuse potential or psychotropic action to be disposed of according to the invention is particularly preferably at least one transdermally and / or topically administrable opioid selected from the group comprising allylprodin, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, Cyclazocine, desomorphine, dextromoramide, decocin, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, Eptazocine, ethoheptazine, ethorphine, ethylmethylthiambutene, ethylmorphine, etonitazene, fentanyl, heroin, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophin, nalbuphine, Narcein, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piriiramide, propheptazine, promedi, propranam, propoxyphene, sufentanil, tramadol and Tilidine, a corresponding stereoisomeric compound, a corresponding derivative, a physiologically acceptable enantiomer, stereoisomer, diastereomer, racemate, a physiologically acceptable derivative thereof, such as ether, ester or amide, and in each case a physiologically acceptable compound, in particular a salt and solvate.
Ganz besonders bevorzugt handelt es sich bei dem erfindungsgemäß zu entsorgenden Wirkstoff mit Missbrauchspotential um wenigstens ein transdermal und/oder topisch verabreichbares Opioid ausgewählt aus der Gruppe umfassend Buprenorphin, Fentanyl und Sufentanil, eine entsprechende stereoisomere Verbindung, ein entsprechendes Derivat, ein physiologisch verträgliches Enantiomeres, Stereoisomeres, Diastereomeres, Racemat, ein davon physiologisch verträgliches Derivat, wie beispielsweise ein Ether, Ester oder Amid, und jeweils eine physiologisch verträgliche Verbindung, insbesondere ein Salz und Solvat, beispielsweise Hydrochlorid.Very particular preference is given to the active ingredient according to the invention with abuse potential to at least one transdermally and / or topically administrable opioid selected from the group comprising buprenorphine, fentanyl and sufentanil, a corresponding stereoisomeric compound, a corresponding derivative, a physiologically acceptable enantiomer, stereoisomer , Diastereomeres, racemate, a physiologically acceptable derivative thereof, such as an ether, ester or amide, and in each case a physiologically acceptable compound, in particular a salt and solvate, for example hydrochloride.
In einer besonders bevorzugten Ausführungsform handelt es sich bei dem erfindungsgemäß zu entsorgenden Wirkstoff mit Missbrauchspotential bzw. psychotroper Wirkung um Buprenorphin.In a particularly preferred embodiment, the active ingredient to be disposed of according to the invention with abuse potential or psychotropic effect is buprenorphine.
Erfindungswesentlich ist, dass die kontrollierte Zerstörung des Wirkstoffes mit Missbrauchspotential nur durch Aufbringen des Entsorgungsmittels auf die wirkstoffhaltige Fläche des Wirkstoffabgabesystems erreicht wird und unmittelbar nach dem ersten Kontakt des Wirkstoffabgabesystems mit dem Entsorgungsmittel beginnt.Essential to the invention is that the controlled destruction of the drug with abuse potential is achieved only by applying the disposal agent on the drug-containing surface of the drug delivery system and begins immediately after the first contact of the drug delivery system with the disposal.
Erfindungsgemäß ist es nicht notwendig das zu entsorgende Wirkstoffabgabesystem in einem Inaktivierungsmittel einzuschließen, wodurch nach wie vor eine Gefahr des
Missbrauchs durch die vorhandene, nicht zerstörte Wirkstoffmenge gegeben ist. Der bekannte Einschluss des zu entsorgenden Wirkstoffabgabesystems ohne Zerstörung des Wirkstoffes wird erfindungsgemäß vermieden, da durch Oberflächenkontakt des Entsorgungsmittels mit dem wirkstoffhaltigen Bereich des WirkstoffabgabesystemsAccording to the invention, it is not necessary to include the drug delivery system to be disposed of in an inactivating agent, which still poses a risk of Abuse by the existing, not destroyed drug amount is given. The known inclusion of the drug delivery system to be disposed of without destruction of the active ingredient is avoided according to the invention, as by surface contact of the disposal agent with the active ingredient-containing region of the drug delivery system
eine kontrollierte Zerstörung des Wirkstoffs unmittelbar nach dem Aufbringen des Entsorgungsmittels beginnt.a controlled destruction of the drug begins immediately after the application of the disposal agent.
Ein weiterer Gegenstand der Erfindung betrifft daher auch ein Verfahren zur kontrollierten Entsorgung und kontrollierten Missbrauchsverhinderung einer in einem zu entsorgenden Wirkstoffabgabesystem vorliegenden Menge eines Wirkstoffes mit Missbrauchspotential, das dadurch gekennzeichnet ist, dass zur Zerstörung der sich in dem wirkstoffhaltigen Bereiches des Wirkstoffabgabesystems befindlichen Menge eines Wirkstoffes ein mehrschichtiges, erfindungsgemäßes Entsorgungsmittel aufgebracht wird und die unmittelbar nach dem Aufbringen des Inaktivierungsmittels auf den wirkstoffhaltigen Bereich einsetzende Zerstörung des Wirkstoffes mindestens bis zu einer für einen Missbrauch völlig ungeeigneten Konzentration des Wirkstoffes, vorzugsweise bis zur vollständigen Vernichtung der noch vorhandenen Wirkstoffmenge fortgeführt wird. Die dafür notwendige Einwirkungsdauer eines Inaktivierungssystems auf den Wirkstoff bzw. auf die vorhandene Wirkstoffmenge kann durch einfache Vorversuche festgestellt werden.Another object of the invention therefore also relates to a method for the controlled disposal and controlled abuse prevention of a present in a drug delivery system to be disposed amount of an active substance with abuse potential, which is characterized in that to destroy the located in the drug-containing portion of the drug delivery system amount of an active ingredient multi-layer, inventive disposal means is applied and immediately after the application of the inactivating agent on the active substance-containing area destruction of the active ingredient is continued at least up to a completely unsuitable for abuse concentration of the active ingredient, preferably until complete destruction of the remaining amount of active ingredient. The necessary duration of action of an inactivation system on the active ingredient or on the amount of active ingredient present can be determined by simple preliminary tests.
Um eine sachgerechte kontrollierte Entsorgung von Wirkstoffabgabesystemen und eine Missbrauchsverhinderung zu gewährleisten, kann einer zum Vertrieb vorgesehenen Verpackung eines Wirkstoffabgabesystems bereits ein davon separat verpacktes, erfindungsgemäßen Entsorgungsmittel beigefügt enthalten, das ggf. nach dem Gebrauch des Wirkstoffabgabesystems ggf. unter ärztlicher Aufsicht zur sachgemäßen Entsorgung des Wirkstoffabgabesystems verwendet wird.
FigurenIn order to ensure a proper controlled disposal of drug delivery systems and prevention of abuse, may be included for distribution of a drug delivery system already separately packaged thereon, disposal according to the invention, if necessary after use of the drug delivery system, if necessary under medical supervision for the proper disposal of the drug delivery system is used. characters
Figur 1 zeigt einen Querschnitt des Entsorgungsmittels (C), das eine für das Inaktivierungssystem undurchlässige Deckschicht (1 ), auf der eine für das Inaktivierungssystem durchlässigen Klebeschicht (6) mit einem ein Inaktivierungssystem (7) enthaltendes Reservoir (2) aufgebracht ist. Das Reservoir (2) ist mit einer für das Inaktivierungssystem durchlässigen Membran (8) verschlossen. Eine für das Inaktivierungssystem undurchlässige Schutzfolie (3) deckt die Klebeschicht ab.Figure 1 shows a cross-section of the disposal means (C) comprising an inactivation system impermeable cover layer (1) having an adhesive layer (6) pervious to the inactivation system with a reservoir (2) containing an inactivation system (7). The reservoir (2) is closed by a membrane (8) permeable to the inactivation system. A protective film (3) impermeable to the inactivation system covers the adhesive layer.
Figur 2 zeigt einen Querschnitt des Entsorgungsmittels (C) mit einer für das Inaktivierungssystem undurchlässigen Deckschicht (1 ) und einer das Inaktivierungssystem enthaltenden und dafür durchlässigen Matrixschicht (5), die mit einer für das Inaktivierungssystem undurchlässigen Schutzfolie (3) abgedeckt ist.Figure 2 shows a cross section of the disposal means (C) with an inactivation system impermeable cover layer (1) and a matrix layer (5) containing and permeable to the inactivation system, covered with a protective film (3) impermeable to the inactivation system.
Figur 3 zeigt einen Querschnitt des Entsorgungsmittels (C), das eine für das Inaktivierungssystem undurchlässige Deckschicht (1 ) und eine das Inaktivierungssystem enthaltende poröse Teilschicht (9) aufweist, in der das Inaktivierungssystem aufgenommen ist. Die poröse Teilschicht (9) ist von einem Kleberand (10) umrandet. Die poröse Teilschicht (9) und der Kleberand (10) sind mit einer für das Inaktivierungssystem undurchlässigen Schutzfolie (3) abgedeckt.Figure 3 shows a cross-section of the disposal means (C) comprising a capping layer (1) impermeable to the inactivation system and a porous sub-layer (9) containing the inactivation system, in which the inactivation system is incorporated. The porous sublayer (9) is bordered by an adhesive edge (10). The porous sub-layer (9) and the adhesive edge (10) are covered with a protective film (3) impermeable to the inactivation system.
Figur 4 zeigt eine Ausführungsform des Entsorgungsmittels (C), mit einer für das Inaktivierungssystem undurchlässigen Deckschicht (1 ). Das kammerförmige Reservoir (2) weist zwei voneinander getrennte Abteilungen (2a, 2b) und eine für das Inaktivierungssystem durchlässige Membran (8) auf. Die Abteilungen sind durch eine für das Inaktivierungssystem undurchlässige Wand (4) getrennt, in denen jeweils eine Komponente (A bzw. B) des Inaktivierungssystems vorliegen. Die membranförmige, für das Inaktivierungssystem durchlässige Schicht ist mit einer Schutzfolie (3) abgedeckt.Figure 4 shows an embodiment of the disposal means (C) with a capping layer (1) impermeable to the inactivation system. The chamber-shaped reservoir (2) has two separate compartments (2a, 2b) and a membrane (8) permeable to the inactivation system. The compartments are separated by a wall (4) impermeable to the inactivation system, each containing one component (A or B) of the inactivation system. The membrane-shaped, permeable for the inactivation system layer is covered with a protective film (3).
Durch leichten Druck kann die Trennwand (4) im Reservoir umgeklappt werden, wodurch die beiden Komponenten A und B miteinander vermischt werden, z. B. durch Auflösen eines Salzes (A) in Wasser (B) zu einer wässrigen Lösung des Salzes wodurch das Inaktivierungssystem erhalten wird.
BeispieleBy slight pressure, the partition (4) can be folded in the reservoir, whereby the two components A and B are mixed together, for. B. by dissolving a salt (A) in water (B) to an aqueous solution of the salt whereby the inactivation system is obtained. Examples
Beispiel 1example 1
a) Herstellung eines Buprenorphin-haltiqen Pflastersa) Preparation of a buprenorphine-containing patch
1139 g einer 48 Gew.%igen Polyacrylatlösung eines selbstvernetzenden Acrylatcopolymeren aus 2-Ethylhexylacrylat, Vinylacetat, Acrylsäure (Lösemittel: EthylacetafcHeptanMsopropanolToluohAcetyiacetonat im Verhältnis von 37:26:26:4:1 ), 100 g Lävulinsäure, 150 g Oleylacetat, 100 g Polyvinylpyrrolidon, 150 g Ethanol, 200 g Ethylacetat und 100 g Buprenorphinbase werden homogenisiert. Man rührt etwa zwei Stunden und kontrolliert visuell, ob alle Feststoffe gelöst sind. Man kontrolliert außerdem den Verdunstungsverlust durch Zurückwiegen und ergänzt gegebenenfalls den Lösemittelverlust durch Zugabe von Ethylacetat.1139 g of a 48% strength by weight polyacrylate solution of a self-crosslinking acrylate copolymer of 2-ethylhexyl acrylate, vinyl acetate, acrylic acid (solvent: ethylacetafcHeptanMsopropanolToluohAcetyiacetonat in the ratio of 37: 26: 26: 4: 1), 100 g of levulinic acid, 150 g of oleyl acetate, 100 g of polyvinylpyrrolidone, 150 g of ethanol, 200 g of ethyl acetate and 100 g of buprenorphine base are homogenized. Stir for about two hours and visually check to see if all solids are dissolved. It also controls the evaporation loss by weighing back and optionally adds the loss of solvent by adding ethyl acetate.
Als Deckschicht wird eine 420 mm breite, transparente Polyesterfolie mit der vorstehend beschriebenen Mischung so beschichtet, dass das Flächengewicht der getrockneten Klebeschicht bei 80 g/m2 liegt.As a cover layer, a 420 mm wide, transparent polyester film is coated with the above-described mixture so that the weight per unit area of the dried adhesive layer is 80 g / m 2 .
Man entfernt die Lösemittel durch Trocknen mit erwärmter Luft, die über die feuchte Bahn geleitet wird. Durch die Wärmebehandlung verdampfen die Lösemittel. Abschließend deckt man die wirkstoffhaltige Klebeschicht mit einer 15 μm dicken Polyesterfolie als Schutzfolie ab, die durch eine Silikonbehandlung wieder ablösbar ist. Mit geeigneten Schneidewerkzeugen stanzt man eine für die vorgesehene Wirkstoffmenge entsprechende Fläche aus.The solvents are removed by drying with heated air which is passed over the wet web. The heat treatment evaporates the solvents. Finally, the active ingredient-containing adhesive layer is covered with a 15 μm thick polyester film as a protective film, which can be removed again by silicone treatment. Using suitable cutting tools, a surface corresponding to the intended amount of active substance is punched out.
b) Herstellung des Entsorαunqsmittelsb) Preparation of the Disposal Agent
Zur Herstellung von erfindungsgemäßen Entsorgungsmittels werden jeweils eine Polyethylenterephthalat-Folie mit einer Dicke von 75 μm als Deckschicht in einem Ericsson-Filmziehgerät (der Fa. Ericsson GmbH & Co. KG, Hemertextilien, Deutschland) eingespannt. Anschließend wird jeweils eine ca. 300 μm dicke, aus Textilmaterial bestehende Teilschicht, die mit einer ca. 20%-igen KMnO4-Lösung getränkt ist, auf die Deckschicht aufgebracht. Ein Kleberand, der aus Acrylat/Vinylacetat-copolymerisat hergestellt wird, wird so angebracht, dass der Rand die aus Textilmaterial bestehende Teilschicht entsprechend (vgl. Figur 3) umfaßt.
Eine aus Polyester bestehende transparente Schutzfolie wird so aufgebracht, dass ihre flächige Ausdehnung sowohl die das Inaktivierungssystem enthaltende Fläche der Textilschicht, als auch den sie umlaufenden Kleberand abdeckt.For the production of disposal according to the invention in each case a polyethylene terephthalate film with a thickness of 75 microns as a cover layer in an Ericsson film applicator (the company Ericsson GmbH & Co. KG, Hemertextilien, Germany) clamped. Subsequently, an approximately 300 .mu.m thick, made of textile material sub-layer, which is impregnated with an approximately 20% KMnO 4 solution, applied to the cover layer. An adhesive edge made of acrylate / vinyl acetate copolymer is applied so that the edge comprises the textile material sub-layer (see Figure 3). A transparent protective film made of polyester is applied in such a way that its areal extent covers both the area of the textile layer containing the inactivation system and the surrounding adhesive edge.
Zur Prüfung der Wirksamkeit des erfindungsgemäßen Entsorgungsmittels wird jeweils ein nach a) hergestelltes Buprenorphin-Pflaster mit jeweils einem erfindungsgemäßen Entsorgungsmittels hergestellt nach b) (nach Ablösen der abziehbaren Schutzfolie) für 2, 6 bzw. 24 Stunden bei 25°C in Kontakt gebracht.In order to test the effectiveness of the disposal agent according to the invention, a buprenorphine plaster produced according to a) is prepared in each case with a disposal agent according to the invention prepared according to b) (after detachment of the peelable protective film) for 2, 6 or 24 hours at 25 ° C.
Danach wird jeweils der Restgehait von Buprenorphin im Pflaster nach herkömmlicher HPLC-Methode bestimmt.Thereafter, the residual content of buprenorphine in the patch is determined by conventional HPLC method.
Die entsprechenden Testergebnisse dieser Messungen sind in der nachfolgendenThe corresponding test results of these measurements are in the following
Tabelle 1 zusammengestellt.Table 1 is compiled.
Tabelle 1 Restgehalt Buprenorphin (%) nach Oh 2Ü 6h 24hTable 1 Remaining Buprenorphine (%) after Oh 2h 6h 24h
*100 % 2,8 % *100 % - 1 ,3 %* 100% 2.8% * 100% - 1, 3%
*100 % - - 0,0 %* 100% - - 0.0%
*100 % Wirkstoffgehalt* 100% active ingredient content
Aus Tabelle 1 geht hervor, dass bereits nach einem zweistündigen Kontakt des Entsorgungsmittels mit dem wirkstoffhaltigen Bereich des Pflasters bei 25°C die anfängliche Menge des Wirkstoffes mit Missbrauchspotential drastisch abgenommen hat und bereits so gering ist, dass kein Missbrauch mehr möglich ist. Nach einem 24higen Kontakt ist kein Wirkstoff mehr analytisch feststellbar.
From Table 1 shows that after only two hours of contact of the disposal agent with the active substance-containing area of the patch at 25 ° C, the initial amount of drug with abuse potential has dropped drastically and is already so low that no more abuse is possible. After a 24-hour contact no active ingredient is analytically detectable.
Claims
1. Ein Entsorgungssystem umfassend1. comprising a disposal system
A) wenigstens ein zu entsorgendes Wirkstoffabgabesystem umfassend wenigstens einen Wirkstoff mit Missbrauchspotential undA) at least one drug delivery system to be disposed of comprising at least one drug with abuse potential and
B) wenigstens ein von dem zu entsorgenden Wirkstoffabgabesystem separiert vorliegendes, mehrschichtiges Entsorgungsmittels mit einem Inaktivierungssystem zur kontrollierten, unmittelbar nach dem Inkontaktbringen des zu entsorgenden Wirkstoffabgabesystems mit dem Entsorgungsmittel einsetzenden Zerstörung der in dem zu entsorgenden Wirkstoffabgabesystem vorhandenen Menge des Wirkstoffes mit Missbrauchspotential.B) at least one separated from the drug delivery system to be disposed of present, multi-layer disposal system with an inactivation system for controlled onset of contacting the disposable drug delivery system with the disposable destruction of existing in the drug delivery system to be disposed amount of drug with abuse potential.
2. Ein Entsorgungssystem gemäß Anspruch 1 , dadurch gekennzeichnet, dass das Entsorgungsmittel und das Wirkstoffabgabesystem eine flächenförmige Ausdehnung aufweist.2. A disposal system according to claim 1, characterized in that the disposal means and the drug delivery system has a sheet-like extension.
3. Ein Entsorgungssystem gemäß Anspruch 1 oder 2, dadurch gekennzeichnet, dass die wirksame Fläche des Entsorgungsmittels wenigstens der Fläche des wirkstoffhaltigen Bereichs des Wirkstoffabgabesystems entspricht.3. A disposal system according to claim 1 or 2, characterized in that the effective area of the disposal means corresponds at least to the area of the active substance-containing area of the active substance delivery system.
4. Ein Entsorgungssystem gemäß einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, dass das Entsorgungsmittel eine für das Inaktivierungssystem durchlässige Schicht aufweist, in der das Inaktivierungssystem in einem Matrixmaterial verteilt, in einem porösen Material aufgenommen oder in einem Reservoir vorliegt.4. A disposal system according to any one of claims 1 to 3, characterized in that the disposal means comprises a permeable for the inactivation system layer in which the inactivation system distributed in a matrix material, taken in a porous material or in a reservoir.
5. Ein Entsorgungssystem gemäß Ansprüche 4, dadurch gekennzeichnet, dass die für das Inaktivierungssystem durchlässige Schicht auf einer ihrer Oberflächen mit einer für das Inaktivierungssystem undurchlässigen Deckschicht verbunden ist.5. A disposal system according to claim 4, characterized in that the permeable to the inactivation system layer is connected on one of its surfaces with a non-impermeable for the inactivation topcoat.
6. Ein Entsorgungssystem gemäß Anspruch 4 oder 5, dadurch gekennzeichnet, dass das Reservoir kammerförmig ist und eine für das Inaktivierungssystem durchlässige Membran, die ggf. der für das Inaktivierungssystem durchlässigen Schicht entspricht, aufweist.6. A disposal system according to claim 4 or 5, characterized in that the reservoir is chamber-shaped and one for the inactivation system permeable membrane, which may correspond to the permeable for the inactivation system layer has.
7. Ein Entsorgungssystem gemäß Anspruch 6, dadurch gekennzeichnet, dass das kammerförmige Reservoir mindestens zwei durch eine Trennwand voneinander getrennte Abteilungen aufweist.7. A disposal system according to claim 6, characterized in that the chamber-shaped reservoir has at least two compartments separated by a partition.
8. Ein Entsorgungssystem gemäß einem der Ansprüche 1 bis 7, dadurch gekennzeichnet, dass die für das Inaktivierungssystem durchlässige Schicht eine Klebeschicht oder einen Kleberand aufweist.8. A disposal system according to any one of claims 1 to 7, characterized in that the permeable for the inactivation system layer has an adhesive layer or an adhesive edge.
9. Ein Entsorgungssystem gemäß einem der Ansprüche 1 bis 8, dadurch gekennzeichnet, dass das Entsorgungsmittel eine angrenzend an die durchlässige Schicht oder die ggf. vorhandene Klebeschicht ablösbare Schutzfolie aufweist.9. A disposal system according to any one of claims 1 to 8, characterized in that the disposal means comprises an adjacent to the permeable layer or the adhesive layer optionally removable protective film.
10. Ein Entsorgungssystem gemäß einem der Ansprüche 1 bis 9, dadurch gekennzeichnet, dass das Inaktivierungssystem in fester, halbfester oder flüssiger Form im Entsorgungsmittel vorliegt.10. A disposal system according to any one of claims 1 to 9, characterized in that the inactivation system is present in solid, semi-solid or liquid form in the disposal means.
11. Ein Entsorgungssystem gemäß Anspruch 10, dadurch gekennzeichnet, dass das Inaktivierungssystem in Form von Kristallen, Granulaten, Pellets, Pastillen, Pulver, in Mikrokapseln, als Lösung oder als Gel in einem Matrixmaterial verteilt, in einem porösen Material, vorzugsweise einem Schwamm aufgenommen, oder in einem Reservoir vorliegt.11. A disposal system according to claim 10, characterized in that the inactivation system in the form of crystals, granules, pellets, lozenges, powder, dispersed in microcapsules, as a solution or as a gel in a matrix material, in a porous material, preferably a sponge, or in a reservoir.
12. Ein Entsorgungssystem gemäß einem Anspruch 10 oder 11 , dadurch gekennzeichnet, dass das Inaktivierungssystem eine den Wirkstoff chemisch inaktivierende Verbindung umfasst.12. A disposal system according to claim 10 or 11, characterized in that the inactivation system comprises a compound chemically inactivating the active substance.
13. Ein Entsorgungssystem gemäß Anspruch 12, dadurch gekennzeichnet, dass das Inaktivierungssystem den Wirkstoff mit Missbrauchspotential oxidativ, reduktiv, alkalisch, sauer oder hydrolytisch zerstört.13. A disposal system according to claim 12, characterized in that the inactivating system destroys the active substance with abuse potential oxidative, reductive, alkaline, acidic or hydrolytic.
14. Ein Entsorgungssystem gemäß einem der Ansprüche 10 bis 13, dadurch gekennzeichnet, dass das Inaktivierungssystem wenigstens eine Säure oder Base umfasst. 14. A disposal system according to any one of claims 10 to 13, characterized in that the inactivation system comprises at least one acid or base.
15. Ein Entsorgungssystem gemäß einem der Ansprüche 10 bis 13, dadurch gekennzeichnet, dass das Inaktivierungssystem wenigstens ein Alkalisalz, vorzugsweise ein Natrium- oder Kaliumsalz einer mit Säure mit oxidativer Wirkung umfasst.15. A disposal system according to any one of claims 10 to 13, characterized in that the inactivation system comprises at least one alkali metal salt, preferably a sodium or potassium salt of an oxidative acid.
16. Ein Entsorgungssystem gemäß einem der Ansprüche 10 bis 15, dadurch gekennzeichnet, dass das Inaktivierungssystem wenigstens eine Verbindung ausgewählt aus der Gruppe umfassend Natriumperborat, Kaliumperborat, Kaliumpermanganat, Benzoylperoxid, Natriumperoxid, Carbamidperoxid, Natriumpercarbonat, Kaliumpercarbonat, Natriumpersulfat, Kaliumpersulfat, Natriumperoxidisulfat, Kaliumperoxidisulfat, Natriumperphosphat, Kaliumperphosphat, H2O2 und Peressigsäure umfasst.16. A disposal system according to any one of claims 10 to 15, characterized in that the inactivation system comprises at least one compound selected from the group comprising sodium perborate, potassium perborate, potassium permanganate, benzoyl peroxide, sodium peroxide, carbamide peroxide, sodium percarbonate, potassium percarbonate, sodium persulfate, potassium persulfate, sodium peroxydisulfate, potassium peroxodisulfate, Sodium perphosphate, potassium perphosphate, H2O2 and peracetic acid.
17. Ein Entsorgungssystem gemäß Anspruch 16, dadurch gekennzeichnet, dass das Inaktivierungssystem einen Aktivator, vorzugsweise Tetraacetyl- ethylendiamin umfasst.17. A disposal system according to claim 16, characterized in that the inactivation system comprises an activator, preferably tetraacetyl-ethylenediamine.
18. Ein Entsorgungssystem gemäß einem der Ansprüche 1-17 dadurch gekennzeichnet, dass das Inaktivierungssystem eine wässrige Kaliumpermanganatlösung ist.18. A disposal system according to any one of claims 1-17, characterized in that the inactivation system is an aqueous potassium permanganate solution.
19. Ein Entsorgungssystem gemäß einem der Ansprüche 1 -18, daruch gekennzeichnet, dass das zu entsorgende Wirkstoffabgabesystem ein System zur transdermalen und/oder topischen Wirkstoffabgabe ist.19. A disposal system according to any one of claims 1 to 18, characterized in that the drug delivery system to be disposed of is a transdermal and / or topical drug delivery system.
20. Ein Entsorgungssystem gemäß einem der Ansprüche 1-19, dadurch gekennzeichnet, dass das zu entsorgende Wirkstoffabgabesystem ein Pflaster ist.20. A disposal system according to any one of claims 1-19, characterized in that the drug delivery system to be disposed of is a plaster.
21. Ein Entsorgungssystem gemäß einem der Ansprüche 1-20, dadurch gekennzeichnet, dass das zu entsorgende Wirkstoffabgabesystem ein gebrauchtes Wirstoffabgabesystem oder ein abgelaufenes, ungebrauchtes Wirkstoffabgabesystem ist.21. A disposal system according to any one of claims 1-20, characterized in that the drug delivery system to be disposed of is a used drug delivery system or an expired, unused drug delivery system.
22. Ein Entsorgungssystem gemäß einem der Ansprüche 1 -21 , dadurch gekennzeichnet, dass der Wirkstoff mit Missbrauchspotential wenigstens ein transdermal und/oder topisch verabreichbarer Wirkstoff aus der Gruppe umfassend Anästhetika, Analgetika, Antieleptika, Antipakinsonmittel, Psycholeptika, Psychoanaleptika und andere Mittel für das Nervensystem ist.22. A disposal system according to any one of claims 1 -21, characterized in that the active substance with Abuse potential at least one transdermally and / or topically administrable active ingredient from the group including anesthetics, analgesics, antielectics, antipakinson agents, psycholeptics, psychoanaleptics and other nervous system agents.
23. Ein Entsorgungssystem gemäß einem der Ansprüche 1 bis 22, dadurch gekennzeichnet, dass der Wirkstoff mit Missbrauchspotential wenigstens ein Opioid, Stimulanz, Tranquilizer (Barbiturat und Benzodiazepin), ein weiteres Betäubungsmittel, eine entsprechende stereoisomere Verbindung, ein entsprechendes Derivat, ein physiologisch verträgliches Enantiomeres, Stereoisomeres, Diastereomeres, Racemat, ein davon physiologisch verträgliches Derivat, wie vorzugsweise ein Ether, Ester oder Amid, und jeweils eine physiologisch verträgliche Verbindung, vorzugsweise ein Salz und Solvat ist.23. A disposal system according to any one of claims 1 to 22, characterized in that the active substance with Abuse potential at least one opioid, stimulant, tranquilizers (barbiturate and benzodiazepine), another anesthetic, a corresponding stereoisomeric compound, a corresponding derivative, a physiologically acceptable enantiomer , Stereoisomer, diastereomer, racemate, a physiologically acceptable derivative thereof, such as preferably an ether, ester or amide, and each is a physiologically acceptable compound, preferably a salt and solvate.
24. Ein Entsorgungssystem gemäß Anspruch 23, dadurch gekennzeichnet, dass der Wirkstoff mit Missbrauchspotential wenigstens ein transdermal und/oder topisch verabreichbares Opioid ausgewählt aus der Gruppe umfassend Sulfentanil, Allylprodin, Alphaprodin, Anileridin, Benzylmorphin, Bezitramid, Buprenorphin, Butorphanol, Clonitazen, Codein, Cyclazocin, Desomorphin, Dextromoramid, Dezocin, Diampromid, Dihydrocodein, Dihydromorphin, Dimenoxadol, Dimepheptanol, Dimethylthiambuten, Dioxaphetylbutyrat, Dipipanon, Eptazocin, Ethoheptazin, Ethorphin, Ethylmethylthiambuten, Ethylmorphin, Etonitazen, Fentanyl, Heroin, Hydrocodon, Hydromorphon, Hydroxypethidin, Isomethadon, Ketobemidon, Levallorphan, Levorphanol, Levophenacylmorphan, Lofentanil, Meperidin, Meptazinol, Metazocin, Methadon, Metopon, Morphin, Myrophin, Nalbuphin, Narcein, Nicomorphin, Norlevorphanol, Normethadon, Nalorphin, Normorphin, Norpipanon, Opium, Oxycodon, Oxymorphon, Papaveretum, Pentazocin, Phenadoxon, Phenomorphan, Phenazocin, Phenoperidin, Piminodin, Piritramid, Propheptazin, Promedol, Properidin, Propiram, Propoxyphen, Sufentanil und Tilidin, eine entsprechende stereoisomere Verbindung, ein entsprechendes Derivat, ein physiologisch verträgliches Enantiomeres, Stereoisomeres, Diastereomeres, Racemat, ein davon physiologisch verträgliches Derivat, vorzugsweise ein Ether, Ester oder Amid, und jeweils eine physiologisch verträgliche Verbindung, vorzugsweise ein Salz und Solvat, bevorzugt Buprenorphin ist. 24. A disposal system according to claim 23, characterized in that the active substance with abuse potential comprises at least one transdermally and / or topically administrable opioid selected from the group comprising sulfentanil, allylprodin, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, Cyclazocine, desomorphine, dextromoramide, decocin, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethorphine, ethylmethylthiambutene, ethylmorphine, etonitazene, fentanyl, heroin, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, Levallorphan, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophin, nalbuphine, narcein, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, Phenomorphan, phen azocine, phenoperidine, piminodin, piritramide, propheptazine, promedol, propperine, propiram, propoxyphene, sufentanil and tilidine, a corresponding stereoisomeric compound, a corresponding derivative, a physiologically acceptable enantiomer, stereoisomer, diastereomer, racemate, a physiologically acceptable derivative thereof, preferably one Ether, ester or amide, and each is a physiologically acceptable compound, preferably a salt and solvate, preferably buprenorphine.
5. Verfahren zur kontrollierten Missbrauchsverhinderung eines in einem5. A method for the controlled abuse prevention in one
Wirkstoffabgabesystem vorliegenden Wirkstoffes mit Missbrauchspotential mit Hilfe eines Entsorgungsmittels gemäß einem der Ansprüche 1 bis 17, dadurch gekennzeichnet, dass zur kontrollierten Zerstörung der sich in dem wirkstoffhaltigen Bereich des Wirkstoffabgabesystems befindlichen Wirkstoffmenge ein mehrschichtiges Entsorgungsmittel auf den wirkstoffhaltigen Bereich nur aufgebracht und die unmittelbar nach dem Aufbringen des Entsorgungsmitteis einsetzende Zerstörung des Wirkstoffes mindestens bis zu einer für einen Missbrauch ungeeigneten Konzentration, vorzugsweise bis zu einer Stufe der vollständigen Vernichtung des Wirkstoffes, fortgeführt wird. Drug delivery system present active substance with abuse potential with the aid of a disposal agent according to one of claims 1 to 17, characterized in that for the controlled destruction of the active substance contained in the drug-containing portion of the drug delivery system, a multi-layer disposal means applied to the active substance-containing area and immediately after application of the Disposal must be initiated destruction of the active substance at least up to an unsuitable for abuse concentration, preferably up to a stage of complete destruction of the active ingredient, continued.
Applications Claiming Priority (2)
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DE102006047270.5 | 2006-10-04 | ||
DE102006047270A DE102006047270A1 (en) | 2006-10-04 | 2006-10-04 | disposal system |
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WO2008040512A3 WO2008040512A3 (en) | 2008-08-28 |
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Cited By (2)
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CN102596438A (en) * | 2009-08-07 | 2012-07-18 | Lts勒曼治疗***股份公司 | Destructive disposal of medical active ingredients in transdermal therapeutic systems |
US11679084B2 (en) | 2019-08-09 | 2023-06-20 | Nopioid, Llc | Method and compositions for rendering opioids safe |
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DE202008004785U1 (en) * | 2008-04-04 | 2009-08-13 | Grünenthal GmbH | disposal device |
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US5804215A (en) * | 1997-03-21 | 1998-09-08 | L. Perrigo Company | Transdermal patch disposal system and method |
WO2002085268A1 (en) * | 2001-04-23 | 2002-10-31 | Euro-Celtique S.A. | Disposal system for transdermal dosage form |
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 |
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2006
- 2006-10-04 DE DE102006047270A patent/DE102006047270A1/en not_active Withdrawn
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- 2007-10-01 WO PCT/EP2007/008506 patent/WO2008040512A2/en active Application Filing
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US5804215A (en) * | 1997-03-21 | 1998-09-08 | L. Perrigo Company | Transdermal patch disposal system and method |
WO2002085268A1 (en) * | 2001-04-23 | 2002-10-31 | Euro-Celtique S.A. | Disposal system for transdermal dosage form |
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 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102596438A (en) * | 2009-08-07 | 2012-07-18 | Lts勒曼治疗***股份公司 | Destructive disposal of medical active ingredients in transdermal therapeutic systems |
US11679084B2 (en) | 2019-08-09 | 2023-06-20 | Nopioid, Llc | Method and compositions for rendering opioids safe |
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DE102006047270A1 (en) | 2008-04-10 |
WO2008040512A3 (en) | 2008-08-28 |
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