CN1160349A - 含有可待因的配方 - Google Patents
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- 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 title claims abstract description 70
- 229960004126 codeine Drugs 0.000 title claims abstract description 35
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 239000000203 mixture Substances 0.000 title description 11
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- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 17
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- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 5
- 241001597008 Nomeidae Species 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
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- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical class O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 3
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- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- DKSZLDSPXIWGFO-BLOJGBSASA-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;phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O.OP(O)(O)=O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC DKSZLDSPXIWGFO-BLOJGBSASA-N 0.000 description 1
- ADVGKWPZRIDURE-UHFFFAOYSA-N 2'-Hydroxyacetanilide Chemical compound CC(=O)NC1=CC=CC=C1O ADVGKWPZRIDURE-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229940086239 acetaminophen 500 mg Drugs 0.000 description 1
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- 239000003093 cationic surfactant Substances 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 229960004415 codeine phosphate Drugs 0.000 description 1
- 229940015563 codeine phosphate 8 mg Drugs 0.000 description 1
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- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000000622 liquid--liquid extraction Methods 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
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- 159000000000 sodium salts Chemical group 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
Classifications
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- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
- A61K47/585—Ion exchange resins, e.g. polystyrene sulfonic acid resin
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- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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Abstract
一种含有效止痛剂量的可待因的固体药剂，所述药剂还包含一成分，可阻止以过滤和溶剂提取法来提取药剂中的可待因，但并不防碍可待因在人的消化系统中的释放。合适的成分包括占重量的1-10％的，特别是纤维素衍生物的涂膜剂、占重量的0.1-3％的阴离子表面活性剂以及占重量的2-15％的离子交换树脂。
Description
本发明涉及含有可待因的固体药剂配方。
可待因是一种广泛用于强止痛制剂的吗啡衍生物。较低剂量的可待因制品，尤其是那些由可待因与对乙酰氨基酸酚(乙酰氨基苯酚)的混合物，在许多国家可无需处方容易地购得，并且是治疗剧痛的非常有效的手段。
从止痛剂中提取可待因并将其转化为吗啡和海洛因是可能的。虽然在大多数情况下此方法不具经济上的可行性，但当非法海洛因原料被禁止并价格上涨时，这就成为可行的了。
用合法获得的制品提取可待因并转化为海洛因的方法已设计出来，被通俗的称为“自制”方法。这里只指出该方法包括拌浆、过滤、和溶剂提取从片剂中提取可待因的原始物理学分离方法，而不公开其细节。
本发明目的在于提供一种固体药剂，并且尤其是片剂，这使上述自制方法更加困难并且如按指明使用并不降低制剂的效果。
本发明的特征在于在含可待因的配方中包含干扰自制方法的赋形剂。优选地，该赋形剂不是干扰该方法的物理过滤和/或溶剂提取步骤，而是干扰其后续的化学步骤。
本发明提供了一种含有效止痛剂量的可待因的固体药剂，所述药剂还包含一定剂量的有效成分，可阻止以过滤和/或溶剂提取法来提取药剂中的可待因，但并不防碍可待因在人的消化系统中的释放，所述成分选自：
(a)药剂总重量的1-10％涂膜剂，
(b)阴离子表面活性剂，以及
(c)离子交换树脂。
用于本发明的优选的涂膜剂是纤维素的衍生物，尤其是羟基丙基甲基纤维素、甲基纤维素和羟基丙基纤维素。涂膜层应有一定的剂量，足以阻碍“自制”方法的提取，但又不足以使药剂在人的消化系统中显示出减慢释放速度的特征。因此，配方中应包含低于药剂总重量的10％的剂量的涂膜剂，优选1-10％而且最优选1-5％。
优选的阴离子表面活性剂为十二烷基硫酸钠、十二烷基醚硫酸钠和任一烷芳基磺酸盐。发明人发现，十二烷基硫酸钠能十分有效地实现目的，所以特别优选它。阴离子表面活性剂的含量优选为药剂总重量的0.1-3％。
优选的离子交换树脂为Polacrilin钾和可药用的酸性阳离子交换树脂，如磺酸阳离子交换树脂或羧酸阳离子交换树脂。离子交换树脂的含量优选为药剂重量的2-15％。
优选的配方只包含可待因作为唯一活性成分，或只包含可待因及对乙酰氨基酚。
进一步的优选的实施方案将通过描述配方的方法的实施例阐明，此方法是把可待因和对乙酰氨基酚片剂与阻止自制可待因提取方法的改进的抵抗物混合。
每一示例的配方含有加入了抗自制的组分的相似的基本配方。片剂可进一步的用含纤维素衍生物的涂膜剂涂膜，涂膜重量在使片剂重量增加约2％和5％范围之间。可是优选地，混合了阴离子表面活性剂的片剂不经涂膜，因为初步实验表明这种混合的效果事实上可能不及单独使用阴离子表面活性剂的效果好。
基本配方如下：
活性成分 对乙酰氨基酚500mg/片和磷酸可待因8mg/片。
粘合剂 如Povindonl K25为3-8％(重量比)或玉米淀粉为5-15％(重量比)。
分解剂 如淀粉甘醇酸钠为3-8％(重量比)。
润滑剂 如硬脂酸镁0.5-1.5％或硬脂酸1-3％。
助流剂 如硅胶0.5-1.5％或滑石1-3％(重量比)。
稀释剂 如淀粉或乳糖残余物作为增溶剂。
实施例1
所需剂量的磷酸可待因和抗自制成分，即一种阴离子表面活性剂或纤维素衍生物，干燥掺入预成粒的对乙酰氨基酚。随后使用常规压制设备将颗粒压缩成片剂。如抗自制成分是纤维素的衍生物，则用含纤维素涂膜剂为片剂涂膜至重量增加5％。实施例2
活性成分，粘合剂，成粒分解剂和抗自制成分，即一种阴离子表面活性剂或纤维素衍生物，被筛滤并加入高剪切搅拌机/成粒机。通过预混后，原料成粉然后在流化床干燥器中部分干燥。部分干燥的产品过筛并返回流化床干燥器中最后干燥。干燥后的颗粒与润滑剂和助流剂(如需要)掺合后压成片剂。如果抗自制成分是纤维素的衍生物，片剂就以纤维素涂膜剂涂膜至增重5％。实施例3
可待因(原始的或其磷酸盐)溶解在适当溶剂中并通过一个可以酸或钠盐形式存在的阳离子交换树脂层，采用何种形式取决于树脂的酸强度。为确保可待因与交换树脂充分粘合，如需要，可待因溶液可循环通过交换层。
如必要，生成的可待因的树脂酸盐干燥并进行筛滤和研磨。如需要，产物粉可成粒(一些产物已相当成粒并具有无需进一步处理即可制成片剂的特性)。
粒状树脂酸盐与粘合剂和分解剂一起在流化床中干燥、通过振荡成粒机筛滤后与润滑剂和助流剂掺合。最后的颗粒压成片剂，而后涂膜至增重2％-5％。
按制剂的合理用法，抗自制成分设计为从片剂中释放，并且不影响可待因的作用或释放率。但是，在体外，该成分具有可阻止可待因非法提取过程中某步骤的特定特性。
根据本发明，含有可待因片剂中的添加剂通过增加处理时间和/或降低提取效果来干扰自制过程。尤其是，添加剂可增加浆液过滤的时间和/或在液一液萃取步骤中乳化两相，使两层不能有效地分离。
如果是纤维素涂膜或阳离子表面活性剂，应选择完全水溶性的，它不会因为在粉碎的片剂浆化时可待因被溶解，而在固体相中残留。涂膜剂通过与水接触形成胶体、结合水相和阻塞过滤并也抑制溶剂提取来干扰自制过程。阴离子表面活性剂通过在溶剂提取过程中乳化溶剂和液相而起作用。离子交换树脂通常是不可溶的并固定可待因使其不能被提取。
根据本发明的片剂配方中含2.5％(重量)的羟甲基丙基纤维素已发现可减少可待因提取近45-65％。0.9％(重量)的十二烷基硫酸钠发现可减少提取近25％，并如果为2.5％(重量)则超过90％。离子交换树脂实验中，Zeolex23A和Amberlite IRP69(一种苯乙烯为基的磺酸阳离子交换树脂)取得了好的结果，都减少可待因提取的约60％。
非常优选地，抗自制成分完全分布在片剂基质中，以便在自制过程前减小成分被物理分离的可能。
虽然本发明的特定实施方案已详述，本发明可用其它特定形式实施，并不脱离本发明的本质特征，这对所属领域技术人员是显见的。本发明的实施方案和实施例都是为说明本发明的而不是对本发明的限制，本发明的范围更由所附权利要求所限定，而不是前面的说明书，所有不超过权利要求等同范围和定义内的改变也将包含在其中。
Claims (14)
1.一种含有效止痛剂量的可待因的固体药剂，所述药剂还包含一定剂量的组分，该组分可以有效阻止采用过滤和/或滤液的溶剂提取法提取药剂中的可待因，但并不妨碍可待因在人消化系统中的释放，所述组分选自：
(a)药剂总重量1-10％的涂膜剂，
(b)阴离子表面活性剂，以及
(c)离子交换树脂。
2.根据权利要求1的固体药剂，其中所述药剂为片剂。
3.根据权利要求2的固体药剂，其中所述组分完全分布在片剂中。
4.根据前述任一权利要求的固体药剂，其中所述组分是一种纤维素衍生物涂膜剂。
5.根据权利要求4的固体药剂，其中所述涂膜剂选自羟丙基甲基纤维素，甲基纤维素和羟基丙基纤维素。
6.根据权利要求4或5的固体药剂，其中所述涂膜剂含量为药剂重量的1-5％。
7.根据权利要求1至3的任一固体药剂，其中所述组分是含量为药剂重量的0.1-3％的阴离子表面活性剂。
8.根据权利要求7的固体药剂，其中所述阴离子表面活性剂选自十二烷基硫酸钠、十二烷基醚硫酸钠或烷芳基磺酸盐。
9.根据权利要求8的固体药剂，其中所述阴离子表面活性剂为十二烷基硫酸钠。
10.根据权利要求1至3的任一固体药剂，所述组分是一种离子交换树脂。
11.根据权利要求10的固体药剂，其中所述离子交换树脂含量为药剂总重量的2-15％。
12.根据权利要求11的固体药剂，其中所述离子交换树脂选自Polacrilin钾或可药用的酸性阳离子交换树脂。
13.根据权利要求12的固体药剂，其中所述离子交换树脂选自磺酸阳离子交换树脂、羧酸阳离子交换树脂或它们的一种盐。
14.根据权利要求10至13的任一固体药剂，其中可待因与离子交换树脂结合。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AUPM8149A AUPM814994A0 (en) | 1994-09-14 | 1994-09-14 | Codeine-containing formulations |
| AUPM8149 | 1994-09-14 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1160349A true CN1160349A (zh) | 1997-09-24 |
| CN1095666C CN1095666C (zh) | 2002-12-11 |
Family
ID=3782668
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| Application Number | Title | Priority Date | Filing Date |
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| CN95195626A Expired - Fee Related CN1095666C (zh) | 1994-09-14 | 1995-09-14 | 含有可待因的配方 |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0781135B1 (zh) |
| CN (1) | CN1095666C (zh) |
| AT (1) | ATE228842T1 (zh) |
| AU (1) | AUPM814994A0 (zh) |
| CZ (1) | CZ286736B6 (zh) |
| DE (1) | DE69529079T2 (zh) |
| ES (1) | ES2188670T3 (zh) |
| HU (1) | HUT77386A (zh) |
| NZ (1) | NZ292847A (zh) |
| PL (1) | PL181260B1 (zh) |
| WO (1) | WO1996008252A1 (zh) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69723248T2 (de) * | 1996-04-10 | 2004-05-27 | Warner-Lambert Co. Llc | Vergällungsstoffe für sympathomimetische aminsalze |
| DE19740983A1 (de) | 1997-09-18 | 1999-04-08 | Warner Lambert Co N D Ges D St | Verfahren zur Erschwerung der Extraktion von Wirkstoffen aus Tabletten |
| PT1041987E (pt) * | 1997-12-22 | 2006-07-31 | Euro Celtique Sa | Forma farmaceutica de dosagem oral, compreendendo uma combinacao de um agonista de opioide e naltrexona |
| GT199900148A (es) | 1998-09-10 | 2001-02-28 | Desnaturalizantes para las sales aminas simpaticomimeticas. | |
| CN100450548C (zh) * | 2006-12-22 | 2009-01-14 | 江苏奥赛康药业有限公司 | 一种波拉克林树脂组合物的口腔贴片及其制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2530563C2 (de) * | 1975-07-09 | 1986-07-24 | Bayer Ag, 5090 Leverkusen | Analgetische Arzneimittel mit vermindertem Mißbrauchspotential |
| US4443428A (en) * | 1982-06-21 | 1984-04-17 | Euroceltique, S.A. | Extended action controlled release compositions |
| GB8629567D0 (en) * | 1986-12-10 | 1987-01-21 | Boots Co Plc | Therapeutic agents |
| US4971785A (en) * | 1988-03-14 | 1990-11-20 | Spectrum Consumer Products Co., Inc. | Non-alcoholic delivery system for orally ingestible active ingredients |
| NZ234587A (en) * | 1989-08-04 | 1991-11-26 | Mcneil Ppc Inc | A chewable pharmaceutical tablet of compressed coated granules |
| DD295988A5 (de) * | 1990-06-26 | 1991-11-21 | Chemie Ag Bitterfeld-Wolfen,De | Codeinpraeparat und verfahren zu seiner herstellung |
-
1994
- 1994-09-14 AU AUPM8149A patent/AUPM814994A0/en not_active Abandoned
-
1995
- 1995-09-14 DE DE69529079T patent/DE69529079T2/de not_active Expired - Lifetime
- 1995-09-14 NZ NZ292847A patent/NZ292847A/en not_active IP Right Cessation
- 1995-09-14 CZ CZ1997773A patent/CZ286736B6/cs not_active IP Right Cessation
- 1995-09-14 PL PL95319160A patent/PL181260B1/pl not_active IP Right Cessation
- 1995-09-14 EP EP95931856A patent/EP0781135B1/en not_active Expired - Lifetime
- 1995-09-14 ES ES95931856T patent/ES2188670T3/es not_active Expired - Lifetime
- 1995-09-14 HU HU9701688A patent/HUT77386A/hu unknown
- 1995-09-14 CN CN95195626A patent/CN1095666C/zh not_active Expired - Fee Related
- 1995-09-14 AT AT95931856T patent/ATE228842T1/de not_active IP Right Cessation
- 1995-09-14 WO PCT/AU1995/000601 patent/WO1996008252A1/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| HUT77386A (hu) | 1998-04-28 |
| ATE228842T1 (de) | 2002-12-15 |
| DE69529079D1 (de) | 2003-01-16 |
| CZ77397A3 (en) | 1997-08-13 |
| PL181260B1 (pl) | 2001-06-29 |
| EP0781135A1 (en) | 1997-07-02 |
| ES2188670T3 (es) | 2003-07-01 |
| EP0781135B1 (en) | 2002-12-04 |
| WO1996008252A1 (en) | 1996-03-21 |
| AUPM814994A0 (en) | 1994-10-06 |
| DE69529079T2 (de) | 2003-11-13 |
| PL319160A1 (en) | 1997-07-21 |
| EP0781135A4 (en) | 1997-12-10 |
| CZ286736B6 (en) | 2000-06-14 |
| CN1095666C (zh) | 2002-12-11 |
| NZ292847A (en) | 1998-11-25 |
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