CN1153475A - 具有活性物质缓释特性的卡巴捷平药物 - Google Patents
具有活性物质缓释特性的卡巴捷平药物 Download PDFInfo
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- carbamazepine
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- 229960000623 carbamazepine Drugs 0.000 title claims abstract description 40
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 title claims abstract description 39
- 239000003814 drug Substances 0.000 title claims abstract description 39
- 239000013543 active substance Substances 0.000 title claims abstract description 9
- 239000000725 suspension Substances 0.000 claims description 13
- 239000004902 Softening Agent Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 239000012752 auxiliary agent Substances 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 239000007900 aqueous suspension Substances 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 235000013773 glyceryl triacetate Nutrition 0.000 claims description 4
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 3
- 239000004926 polymethyl methacrylate Substances 0.000 claims description 3
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 3
- 239000001069 triethyl citrate Substances 0.000 claims description 3
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 3
- 235000013769 triethyl citrate Nutrition 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 2
- 229920000193 polymethacrylate Polymers 0.000 claims description 2
- QLIBJPGWWSHWBF-UHFFFAOYSA-N 2-aminoethyl methacrylate Chemical compound CC(=C)C(=O)OCCN QLIBJPGWWSHWBF-UHFFFAOYSA-N 0.000 claims 1
- 229920002367 Polyisobutene Polymers 0.000 claims 1
- 150000004702 methyl esters Chemical class 0.000 claims 1
- QMMOXUPEWRXHJS-UHFFFAOYSA-N pent-2-ene Chemical group CCC=CC QMMOXUPEWRXHJS-UHFFFAOYSA-N 0.000 claims 1
- 239000013078 crystal Substances 0.000 abstract description 10
- 239000002775 capsule Substances 0.000 abstract description 5
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- 239000004815 dispersion polymer Substances 0.000 abstract 1
- 239000010408 film Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 229940079593 drug Drugs 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 150000004683 dihydrates Chemical class 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
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- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical group CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- -1 azepine-5-carboxamide chemical compound Chemical class 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000003578 releasing effect Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 229960000278 theophylline Drugs 0.000 description 2
- XSHISXQEKIKSGC-UHFFFAOYSA-N 2-aminoethyl 2-methylprop-2-enoate;hydron;chloride Chemical compound Cl.CC(=C)C(=O)OCCN XSHISXQEKIKSGC-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 241001530209 Swertia Species 0.000 description 1
- 229920006221 acetate fiber Polymers 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- UPTJXAHTRRBMJE-UHFFFAOYSA-N benzo[b][1]benzazepine-11-carboxamide;dihydrate Chemical compound O.O.C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 UPTJXAHTRRBMJE-UHFFFAOYSA-N 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
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- 229920001577 copolymer Polymers 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
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- 238000004090 dissolution Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 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
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
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- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
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- 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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
- A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
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- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
公开一种具有活性物质缓释特性的口服卡巴捷平药物。在卡巴捷平晶体上施用一种水性塑料聚合物分散液，不会造成卡巴捷平二水合物的生成。带有水性涂层的卡巴捷平晶体可以与适宜助剂混合，成型为单个药片或填入胶囊中。
Description
本发明涉及一种口服的具有活性物质缓释特性的卡巴捷平(Carbamazepine)药物。
卡巴捷平是一种5H-二苯基[b，f]吖庚因-5-甲酰胺化合物，特别用作抗癫癎药。
市场上供应的药物形式为含200mg活性物质的药片，含200mg到600mg活性物质的缓慢作用药片及糖浆。
人们已知该药物与水接触短时间内就形成二水化物。这种二水化物为针状结晶，可生长成500μm大小的晶体。在进一步加工过程中，特别是制造延缓作用的保护膜时会造成困难。
因此在现有的制造方法中人们不用水性介质而优先选择有机溶剂。
使活性物质延缓释放有多种方式方法。在DE-PS3277520专利中描述了一种对卡巴捷平的成型方法，即将活性物质与常用的制片助剂混合压成片芯或装入胶囊，再用溶解在异丙醇中的含作为软化剂的乙酰三丁基柠檬酸酯的甲基丙烯酸与甲基丙烯酸甲酯的混合物制成保护膜。采用一种有机溶剂防止了卡巴捷平二水化物的生成。
专利DE-PS3868077及DE-PS3725824中提出了一种卡巴捷平加含保护胶体的助剂的配方可以阻止在水作用下晶体的生长。这里是将卡巴捷平的药片芯用醋酸纤维溶液包裹，再在薄膜中用适当的方法穿孔作为通道。
前面提出的制造过程中存在的缺点是必须用有机溶剂进行操作，结果是造成环境污染而且制造成本也高。
此外，按上述方法制成的药片(药片及胶囊)不可分成小片。因为分开后就破坏了保护膜，从而延缓作用也消失。
因而限制了剂量的使用范围。
近来也提出了一些制造方法(药片)，当药片在分割或在肠胃的侧壁外或内部分散时不会丧失其延缓作用。在杂志“Pharm.Ind.55 Nr.10(1993)940-947页”中提出了固形口服药的制备方法，即将药粉用甲基丙烯酸与甲基丙烯酸甲酯的共聚物在水中的悬浮液包裹后压制成片。加入25-50％助剂可以加速药片的分解。再通过加入软化剂以显著提高保护膜的抗撕裂延伸性能以保证其机械稳定性。
采用这种保护膜的例子有副乙酰胺制剂(Paracetamol)，氯化钾，阿司匹灵晶体，茶叶碱颗粒，吲哚药片，茶叶碱药片等。
本发明的主要目的是提供一种制造卡巴捷平药片的成型方法。其中虽用水作为溶剂或分散剂，但要防止晶体生长以保证药物具有足够的延缓释放效果。
本发明目的的解决办法如下：成膜剂与一种软化剂结合作为水溶液和/或悬浮液喷洒在卡巴捷平药物表面。表面用薄膜覆盖的药物再与制片助剂混合压成药片或装入胶囊。
作为卡巴捷平药物的缓释剂可用能形成薄膜的聚甲基丙烯酸酯的悬浮液。优先可采用：
-由聚乙基丙烯酸酯与聚甲基异丁烯酸酯按2∶1比例混合成的混合物(欧得拉基NE30D)。
-由聚乙基丙烯酸酯，聚甲基异丁烯酸酯与聚三甲基氨乙基异丁烯酸酯氯化物按1∶2∶0.1比例混合的混合物(欧得拉基RS 30 D)或
-由上述物料按1∶2∶0.2比例混合的混合物(欧得拉基RL30D)。
作为水溶性软化剂可用例如三醋酸甘油或三乙基柠檬酸酯。成膜剂与软化剂按1∶0.05到1∶0.25比例混合，优先采用1∶0.15到1∶0.22比例。
成膜剂与卡巴捷平药物的比例可按对缓释效果的要求决定，一般为1∶0.03到1∶0.5。药物对成膜剂的比例的特定范围为1∶0.05到1∶0.1，优先采用1∶0.05到1∶0.08。
按照不同的卡巴捷平药物与成膜剂的比值得出的释放曲线如图1所示。测定方法是采用USP XXll中对卡巴捷平的溶解试验法(介质为含1％十二烷基硫酸钠的水)。
令人惊异的是按照本发明的配方制成的卡巴捷平药物成品，可以防止在与水接触时出现熟知的立即形成二水化物，而发展成针状结晶，在药物加工时造成的困难。
比较有利的是将与软化剂结合的成膜剂作为水溶液和/或悬浮液在沸腾床制粒机中喷洒到药物上。
为了避免涂膜后的颗粒粘在一起可在悬浮液中添加一种隔离物质和/或在沸腾床中分别进行喷洒这种隔离物质的悬浮液。
例如用滑石粒作为隔离物质，可与油漆干燥剂混合，浓度为1∶0.4到1∶1，优先采用1∶0.45到1∶0.55。
涂膜后的卡巴捷平晶粒还可按照处方要求以通常方法与另一些辅助药物混合。这样制成的混合药物或涂膜晶粒单独装入硬质胶囊中或压制成可分割使用的药片。在进一步加工过程中或特别在分割药片时的机械力不会损坏晶粒表面的薄膜。
这样制成的药物显示出与涂膜的卡巴捷平晶粒同样的推迟溶解速度的效果，即用USP XXll对卡巴捷平的测试法，(结果示于图2中)。
下列实例将进一步说明本发明制造过程的细节：
实例1
用2.23kg欧得拉基RS 30 D，135g三醋酸甘油溶解在2.35升水及325g滑石粉悬浮在1升水中制成悬浮液。在沸腾床制粒机WSG15(Fa.Glatt)中将悬浮液喷洒在10kg卡巴捷平药物上。接着用625g滑石粉在2升水中的悬浮液喷洒。制成的药粒与914g微晶纤维素、653g不溶解的聚烯酮，70g高度分散的二氧化硅及35g硬脂酸镁混合。将混合物压制成含卡巴捷平有效成份200，400或600mg的药片或将相当药量装入1号胶囊中。
实例2
用340g欧得拉基RS 30 D，20.4g三乙基柠檬酸酯溶解在0.3升水中及40g滑石粉悬浮在0.1升水中制成悬浮液。在沸腾床制粒机GPCGl(Fa.Glatt)中27-30℃温度下将悬浮液喷洒在1kg卡巴捷平药物上。制成的药粒与65g微晶纤维素，65g不溶解的聚烯酮，7g高度分散的二氧化硅及3.5g硬脂酸镁混合。将混合物压制成含有效成份200，400或600mg卡巴捷平的药片或将相当含量的药物装入1号胶囊中。
实例3
用29g欧得拉基NE 30 D，1.3g三醋酸甘油溶解在0.03升水中及9g滑石粉悬浮在0.03升水中制成悬浮液。在沸腾床制粒机UN1 Glatt中27-30℃温度下将悬浮液喷射到250g卡巴捷平药物上。然后将制成的颗粒与16g微晶纤维素，16g不溶解的聚烯酮，2g高度分散的二氧化硅及1g硬脂酸镁混合。将混合物压制成含有效卡巴捷平药物200，400或600mg的药片或将相当药量装入1号胶囊中。
Claims (9)
1.具有活性物质缓释特性的卡巴捷平药物，其特征在于其中的成膜剂与软化剂结合作为水溶液和/或悬浮液涂布在卡巴捷平药物上。
2.权利要求1中的卡巴捷平药物，其特征在于以聚甲基丙烯酸酯混合物如聚乙基丙烯酸酯与聚异丁烯酸甲酯按2∶1比例混合；聚乙基丙烯酸酯，聚甲基异丁烯酸酯与聚三甲基氨乙基异丁烯酸酯按1∶2∶0.1或1∶2∶0.2比例混合作为成膜剂。
3.权利要求1中的卡巴捷平药物，其特征在于以三醋酸甘油或三乙基柠檬酸酯为软化剂。
4.权利要求1到3中的卡巴捷平药物，其特征在于成膜剂与软化剂以1∶0.05到1∶0.25的比例结合使用。
5.权利要求4中的卡巴捷平药物，其特征在于使用的成膜剂对软化剂的比例更优选是1∶0.15到1∶0.22。
6.权利要求1到5中的卡巴捷平药物，其特征在于涂膜后的药物还可与其他助剂混合压制成可分割的药片或装入胶囊。
7.权利要求1到6中的卡巴捷平药物，其特征在于涂膜后的卡巴捷平可以不加任何助剂装入胶囊。
8.权利要求1的卡巴捷平药物的制造方法，其特征在于与软化剂结合的成膜剂是以水溶液和/或悬浮液的形式在沸腾床制粒机中喷洒在卡巴捷平药物上。
9.权利要求1的制造方法，其特征在于需要时在成膜剂的悬浮液中加入隔离物料，如滑石粉以1∶0.4到1∶1的比例和/或在沸腾床制粒机中作为单独的悬浮液在最后喷洒在药物上。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19944423078 DE4423078B4 (de) | 1994-07-01 | 1994-07-01 | Verfahren zur Herstellung einer Carbamazepin-Arzneiform mit verzögerter Wirkstofffreisetzung |
| DEP4423078.8 | 1994-07-01 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1153475A true CN1153475A (zh) | 1997-07-02 |
| CN1101191C CN1101191C (zh) | 2003-02-12 |
Family
ID=6522000
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN95193915A Expired - Fee Related CN1101191C (zh) | 1994-07-01 | 1995-06-22 | 具有活性物质缓释特性的卡巴捷平药物 |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US5888545A (zh) |
| EP (1) | EP0768882B1 (zh) |
| JP (1) | JPH10502358A (zh) |
| KR (1) | KR100344477B1 (zh) |
| CN (1) | CN1101191C (zh) |
| AT (1) | ATE169818T1 (zh) |
| BG (1) | BG62794B1 (zh) |
| BR (1) | BR9508202A (zh) |
| CA (1) | CA2194216A1 (zh) |
| CZ (1) | CZ288028B6 (zh) |
| DE (2) | DE4423078B4 (zh) |
| DK (1) | DK0768882T3 (zh) |
| EE (1) | EE03954B1 (zh) |
| ES (1) | ES2122630T3 (zh) |
| GE (1) | GEP19991819B (zh) |
| HU (1) | HU221486B (zh) |
| LT (1) | LT4251B (zh) |
| LV (1) | LV11820B (zh) |
| PL (1) | PL180979B1 (zh) |
| RU (1) | RU2141825C1 (zh) |
| SK (1) | SK282303B6 (zh) |
| UA (1) | UA32598C2 (zh) |
| WO (1) | WO1996001112A1 (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108125922A (zh) * | 2018-01-14 | 2018-06-08 | 上海安必生制药技术有限公司 | 一种卡马西平口服缓释制剂及其制备方法 |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6162466A (en) * | 1999-04-15 | 2000-12-19 | Taro Pharmaceutical Industries Ltd. | Sustained release formulation of carbamazepine |
| RU2007143556A (ru) * | 2005-04-25 | 2009-06-10 | ТЕВА ФАРМАСЬЮТИКАЛЗ ЮЭсЭй, ИНК. (US) | Композиции с пролонгированным высвобождением |
| PL1931346T3 (pl) * | 2005-09-09 | 2013-01-31 | Angelini Labopharm Llc | Kompozycja trazodonu do podawania raz na dobę |
| US20070160960A1 (en) * | 2005-10-21 | 2007-07-12 | Laser Shot, Inc. | System and method for calculating a projectile impact coordinates |
| FR2940910A1 (fr) * | 2009-01-09 | 2010-07-16 | Vetoquinol Sa | Nouveau comprime a base de s-adenosyl-methionine |
| CN105997916A (zh) * | 2016-07-19 | 2016-10-12 | 南京正宽医药科技有限公司 | 一种卡马西平片及其制备方法 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK150008C (da) * | 1981-11-20 | 1987-05-25 | Benzon As Alfred | Fremgangsmaade til fremstilling af et farmaceutisk oralt polydepotpraeparat |
| SE8203953D0 (sv) * | 1982-06-24 | 1982-06-24 | Astra Laekemedel Ab | Pharmaceutical mixture |
| DK151608C (da) * | 1982-08-13 | 1988-06-20 | Benzon As Alfred | Fremgangsmaade til fremstilling af et farmaceutisk peroralt polydepotpraeparat med kontrolleret afgivelse |
| CH668187A5 (de) * | 1986-08-07 | 1988-12-15 | Ciba Geigy Ag | Therapeutisches system mit systemischer wirkung. |
| IL86211A (en) * | 1987-05-04 | 1992-03-29 | Ciba Geigy Ag | Oral forms of administration for carbamazepine in the forms of stable aqueous suspension with delayed release and their preparation |
| US5326572A (en) * | 1989-03-23 | 1994-07-05 | Fmc Corporation | Freeze-dried polymer dispersions and the use thereof in preparing sustained-release pharmaceutical compositions |
-
1994
- 1994-07-01 DE DE19944423078 patent/DE4423078B4/de not_active Expired - Fee Related
-
1995
- 1995-06-22 CN CN95193915A patent/CN1101191C/zh not_active Expired - Fee Related
- 1995-06-22 DE DE59503283T patent/DE59503283D1/de not_active Expired - Lifetime
- 1995-06-22 SK SK1646-96A patent/SK282303B6/sk not_active IP Right Cessation
- 1995-06-22 PL PL95317996A patent/PL180979B1/pl unknown
- 1995-06-22 JP JP8503611A patent/JPH10502358A/ja not_active Ceased
- 1995-06-22 EE EE9600202A patent/EE03954B1/xx unknown
- 1995-06-22 DK DK95922407T patent/DK0768882T3/da active
- 1995-06-22 ES ES95922407T patent/ES2122630T3/es not_active Expired - Lifetime
- 1995-06-22 EP EP95922407A patent/EP0768882B1/de not_active Expired - Lifetime
- 1995-06-22 GE GEAP19953512A patent/GEP19991819B/en unknown
- 1995-06-22 KR KR1019960707549A patent/KR100344477B1/ko not_active IP Right Cessation
- 1995-06-22 CA CA002194216A patent/CA2194216A1/en not_active Abandoned
- 1995-06-22 WO PCT/DE1995/000805 patent/WO1996001112A1/de active IP Right Grant
- 1995-06-22 US US08/776,266 patent/US5888545A/en not_active Expired - Lifetime
- 1995-06-22 HU HU9603565A patent/HU221486B/hu unknown
- 1995-06-22 RU RU97101469A patent/RU2141825C1/ru active
- 1995-06-22 BR BR9508202A patent/BR9508202A/pt not_active Application Discontinuation
- 1995-06-22 AT AT95922407T patent/ATE169818T1/de active
- 1995-06-22 CZ CZ19963826A patent/CZ288028B6/cs not_active IP Right Cessation
- 1995-06-22 UA UA97010403A patent/UA32598C2/uk unknown
-
1996
- 1996-12-28 BG BG101080A patent/BG62794B1/bg unknown
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1997
- 1997-01-30 LV LVP-97-13A patent/LV11820B/lv unknown
- 1997-01-30 LT LT97-012A patent/LT4251B/lt not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108125922A (zh) * | 2018-01-14 | 2018-06-08 | 上海安必生制药技术有限公司 | 一种卡马西平口服缓释制剂及其制备方法 |
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