CN1946379B - 含有托拉塞米和基质成型聚合物的延长释放组合物 - Google Patents
含有托拉塞米和基质成型聚合物的延长释放组合物 Download PDFInfo
- Publication number
- CN1946379B CN1946379B CN2005800093895A CN200580009389A CN1946379B CN 1946379 B CN1946379 B CN 1946379B CN 2005800093895 A CN2005800093895 A CN 2005800093895A CN 200580009389 A CN200580009389 A CN 200580009389A CN 1946379 B CN1946379 B CN 1946379B
- Authority
- CN
- China
- Prior art keywords
- torasemide
- matrix
- forming polymer
- release composition
- prolongation release
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- NGBFQHCMQULJNZ-UHFFFAOYSA-N Torsemide Chemical compound CC(C)NC(=O)NS(=O)(=O)C1=CN=CC=C1NC1=CC=CC(C)=C1 NGBFQHCMQULJNZ-UHFFFAOYSA-N 0.000 title claims abstract description 49
- 229960005461 torasemide Drugs 0.000 title claims abstract description 49
- 239000000203 mixture Substances 0.000 title claims abstract description 46
- 229920000642 polymer Polymers 0.000 title claims description 19
- 230000002035 prolonged effect Effects 0.000 title abstract 2
- 229920002907 Guar gum Polymers 0.000 claims description 5
- 239000001913 cellulose Substances 0.000 claims description 5
- 229920002678 cellulose Polymers 0.000 claims description 5
- 239000000665 guar gum Substances 0.000 claims description 5
- 235000010417 guar gum Nutrition 0.000 claims description 5
- 229960002154 guar gum Drugs 0.000 claims description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical group [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
- 239000002398 materia medica Substances 0.000 claims description 4
- DMBUODUULYCPAK-UHFFFAOYSA-N 1,3-bis(docosanoyloxy)propan-2-yl docosanoate Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCCCCCC DMBUODUULYCPAK-UHFFFAOYSA-N 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 3
- 235000010980 cellulose Nutrition 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 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 claims description 3
- 239000000314 lubricant Substances 0.000 claims description 3
- 229920000609 methyl cellulose Polymers 0.000 claims description 3
- 239000001923 methylcellulose Substances 0.000 claims description 3
- 235000010981 methylcellulose Nutrition 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 239000008107 starch Substances 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- 239000001506 calcium phosphate Substances 0.000 claims description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 2
- 235000011010 calcium phosphates Nutrition 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 229920001577 copolymer Polymers 0.000 claims description 2
- 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 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims description 2
- -1 hydroxypropyl Chemical group 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- 235000019359 magnesium stearate Nutrition 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 2
- 239000011159 matrix material Substances 0.000 claims 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims 1
- 229920003090 carboxymethyl hydroxyethyl cellulose Polymers 0.000 claims 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 230000001882 diuretic effect Effects 0.000 abstract description 5
- 239000002934 diuretic Substances 0.000 abstract description 4
- 206010027566 Micturition urgency Diseases 0.000 abstract 1
- 239000004480 active ingredient Substances 0.000 abstract 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 6
- 241000282414 Homo sapiens Species 0.000 description 5
- 206010022998 Irritability Diseases 0.000 description 4
- 241001597008 Nomeidae Species 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000027939 micturition Effects 0.000 description 4
- 208000004880 Polyuria Diseases 0.000 description 3
- 230000036470 plasma concentration Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229920001661 Chitosan Polymers 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000037058 blood plasma level Effects 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 208000008967 Enuresis Diseases 0.000 description 1
- 229920003141 Eudragit® S 100 Polymers 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229940045110 chitosan Drugs 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 229960003883 furosemide Drugs 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 208000005346 nocturnal enuresis Diseases 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229940068984 polyvinyl alcohol Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- 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
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- 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
- A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
含有托拉塞米作为活性成分的缓释利尿组合物。本发明的细合物可用于避免由常规的即释组合物引起的令人苦恼的尿急。
Description
发明领域
本发明涉及含有托拉塞米作为活性成分的延长释放利尿组合物。
附图的简要说明
图1显示了即释(IR)托拉塞米片剂和实施例8所述的延长释放(PR)托拉塞米片剂的体外释放率(积累值)比较曲线。
图2显示了即释(IR)托拉塞米片剂和实施例8所述的延长释放(PR)托拉塞米片剂的体外释放率的比较曲线。
图3显示了即释(IR)托拉塞米片剂和实施例8所述的延长释放(PR)托拉塞米片剂给药后的人体内血浆浓度比较曲线。
图4显示了即释(IR)托拉塞米片剂和实施例8所述的延长释放(PR)托拉塞米片剂给药后人体内产生尿急次数相对于时间的比较曲线。
背景技术
托拉塞米(US 4018929)是一种具有广泛临床应用的有效利尿剂。托拉塞米主要通过在Henle’s循环上升段抑制钠的再吸收来发挥作用(Puschett JB和Jordan LL，托拉基米在人体内的作用方式，药物学和临床药物学进展，1990；8(1)：7-13)。托拉塞米干扰腔细胞膜上的Na+2Cl-K+泵，并阻碍基侧氯化物的传导(Greger R，托拉塞米对厚层Henle循环上升段活性NaCl再吸收的抑制作用，Arzneim Forsch./Drug Res.1988；38(1)：151-155)。
口服后托拉塞米的生物利用度达到80-90％，其动力学特征为线形，以及消亡半衰期为3-4小时。其药物代谢动力学图谱的特征是最大血浆浓度(Cmax)在相当短的时间内(tmax：约1小时)达到峰值并快速消亡(t1/2：约3-4小时)(Neugebauer G，Besenfelder E和E.托拉塞米在人体内的药物代谢动力学和代谢，Arzneim Forsch./Drug Res.1988；38(1)：164-166)。托拉塞米在剂量2.5-20毫克范围内显示了与尿量间的线性响应关系。钠的排泄物对钾的作用影响很小。(Scheen AJ.托拉塞米在健康志愿者体内的响应曲线，ArZneim Forsch./Drug Res.1988；38(1)：156-159；Barr WH等人，药物代谢动力学与药效学的托拉塞米剂量比例，药物学与临床药物学进展，1990；8(1)：29-37)。口服后约2小时能观察到托拉塞米对尿及电解质排泄物的最大影响(Lesne M.托拉塞米和呋塞米在健康志愿者体内的药物代谢动力学和药效的比较，Arzneim Forsch./Drug Res.1988；38(1)：160-163)。所有这些影响在临床上明显表现为急性多尿，间歇性尿急和耻骨弓不适(Lambe R，KennedyO，Kenny M和Darragh A.托拉塞米的口服或静脉给药在健康志愿者体内的耐受和利尿特性的研究.Eur J Clin Pharmacol 1986；31(Suppl)：9-14)。
因此，托拉塞米组合物的应用，其可避免由常规的即释组合物引起的令人苦恼的原急，因此引起很大的兴趣。
发明概述
本发明的目的是制备利尿组合物，其可以提供更稳定血浆水平的托拉塞米以避免初始的峰值。这提供了具有更少波动和更稳定水平的动力学图谱。因此，原急的频率降低了，这使得需要使用托拉塞米进行治疗的患者更加舒适。
本发明的组合物包括作为活性成分的托拉塞米，以及选自基质成型聚合物的赋形剂，例如，丙烯酸、纤维素、甘油山嵛酸酯、瓜尔胶、黄原胶、壳聚糖、明胶、聚乙烯醇等的聚合物。在每一个组合物中可以仅使用一种聚合物或它们的混合物。构成本发明组合物的其它成分是药物学技术中常规的赋形剂，包括稀释剂，例如乳糖、纤维素、甘露醇、磷酸钙等，以及它们的混合物；粘合剂和崩解剂，例如200、淀粉等，以及它们的混合物；润滑剂，例如硬脂酸镁、滑石粉等，以及它们的混合物。通常地，本发明的组合物中活性成分的含量为0.5-20％，以及基质成型聚合物的含量为1-40％。
本发明的组合物是进行口服给药的片剂。
本发明的组合物能维持利尿作用达最长24小时，优选为前12小时的范围；因此，避免了可能的夜遗尿的打搅。由于给药后获得的血浆水平Cmax很小，防止了由即释组合物引起的令人苦恼的尿急。
发明详述
本发明的片剂含有活性成分托拉塞米，含量为0.5-20mg。实践中，优选每片的剂量是5、10和20mg。基质成型聚合物选自下述的组：1)丙烯酸聚合物，例如(卡波姆-丙烯酸聚合体的聚合物)，
(甲基丙烯酸共聚物)，及其它们的类似物和衍生物；2)纤维素聚合物，例如，(羟丙基甲基纤维素)，甲基纤维素，羧甲基纤维素钠，(羟乙基纤维素)，及其它们的类似物或衍生物；3)
(甘油山嵛酸酯)；4)
(瓜尔胶)及其类似物和衍生物；5)黄原胶；6)壳聚糖；7)明胶；和8)聚乙烯醇及其衍生物。
本发明的组合物含有比例为0.5-20％的活性成分托拉塞米和比例为1-40％的基质成型聚合物。发现最方便的基质成型聚合物是瓜尔胶，优选的含量是4％。然而，其它的基质成型聚合物也可以用在组合物中；其含量可以在一个相对宽的范围内改变。因此，所述的的浓度是1-20％，优选10％，
甲基纤维素的浓度是1-50％，优选40％，和的浓度是1-40％，优选20％，的浓度是1-40％，优选15％，和
的浓度是1-40％，优选4％。
本发明的片剂按照制药技术中的标准方法进行直接压缩或湿粒化，在这种方法中得到的干颗粒的水分含量小于10％。
使用2/叶片搅拌装置(根据美国药典)在50rpm对本发明的片剂进行体外溶出测试。
为了获得完全模拟生理环境的溶出图谱，在最初的2小内检测在pH值为1时进行，随后pH值变为6.8。得到的结果显示在图1和2中。图1显示了托拉塞米的释放(积累值)，以及图2显示了托拉塞米的释放。
本发明将通过以下实施例进行进一步说明，但不局限于此。
实施例1：5mg托拉塞米片剂和，总重量为85mg
实施例2：5mg托拉塞米片剂和，总重量为100mg
实施例3：5mg托拉塞米片剂和
，总重量为85mg
实施例4：5mg托拉塞米片剂和，总重量为100mg
实施例5：10mg托拉塞米片剂和，总重量为85mg
实施例6：5mg托拉塞米片剂和，总重量为100mg
实施例7：5mg托拉塞米片剂和，总重量为85mg
实施例8：10mg托拉塞米片剂和，总重量为170mg
实施例9：20mg托拉塞米片剂和
，总重量为340mg
实施例10：托拉塞米在人体内的药物代谢动力学
对十名健康志愿者的组进行随机临床试验，让其交叉服用10毫克延长释放托拉塞米片剂和10毫克市售的即释托拉塞米片剂(Novag，Spain)。每种片剂的服用间隔时间为1周。延长释放托拉塞米组合物表现出更低的血浆水平峰值(Cmax)，短期(tmax)得到具有更平稳的水平和更少的波动(图3)。延长释放组合物比即释组合物产生了更低频率的急性多尿情况(图4)。
这些数据显示，本发明的托拉塞米组合物比即释组合物产生了更低的血浆水平峰值和更少的波动。此外，在延长释放托拉塞米组合物后具有次数更少的尿急情况。
Claims (11)
1.含有0.5-20重量％托拉塞米作为活性成分并含有1-40重量％基质成型聚合物的延长释放组合物，其中基质成型聚合物选自丙烯酸聚合物、纤维素基质成型聚合物、甘油山嵛酸酯、瓜尔胶及其混合物，其中纤维素基质成型聚合物选自羟丙基甲基纤维素、甲基纤维素、羧甲基纤维素、羟乙基纤维素，和其药物学上可接受的盐及其混合物。
2.根据权利要求1所述的延长释放组合物，其中所述组合物是进行口服给药的片剂。
3.根据权利要求1所述的延长释放组合物，其中基质成型聚合物是瓜尔胶。
4.根据前述权利要求3所述的延长释放组合物，其中基质成型聚合物是
5.根据权利要求1所述的延长释放组合物，其中托拉塞米的含量为4-10重量％。
6.根据权利要求1所述的延长释放组合物，其中基质成型聚合物的含量为2-40重量％。
7.根据权利要求1所述的延长释放组合物，另外包括一种或多种赋形剂，其选自稀释剂、粘合剂、崩解剂和润滑剂。
8.根据权利要求7所述的延长释放细合物，其中稀释剂选自乳糖、纤维素、甘露醇、磷酸钙，和其混合物。
9.根据权利要求7所述的延长释放组合物，其中粘合剂选自淀粉，和其混合物。
10.根据权利要求7所述的延长释放组合物，其中崩解剂选自
200、淀粉，和其混合物。
11.根据权利要求7所述的延长释放组合物，其中润滑剂选自硬脂酸镁、滑石粉，和其混合物。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200400740A ES2244324B1 (es) | 2004-03-25 | 2004-03-25 | Composiciones diureticas de liberacion prolongada. |
| ESP200400740 | 2004-03-25 | ||
| PCT/EP2005/051340 WO2005092291A1 (en) | 2004-03-25 | 2005-03-23 | Prolonged-release compositions comprising torasemide and a matrix-forming polymer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1946379A CN1946379A (zh) | 2007-04-11 |
| CN1946379B true CN1946379B (zh) | 2012-05-16 |
Family
ID=34962072
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2005800093895A Expired - Fee Related CN1946379B (zh) | 2004-03-25 | 2005-03-23 | 含有托拉塞米和基质成型聚合物的延长释放组合物 |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US20080187585A1 (zh) |
| EP (1) | EP1732517B1 (zh) |
| JP (1) | JP4871258B2 (zh) |
| KR (1) | KR101203763B1 (zh) |
| CN (1) | CN1946379B (zh) |
| AR (1) | AR048432A1 (zh) |
| AU (1) | AU2005227095B2 (zh) |
| BR (1) | BRPI0509165A (zh) |
| CA (1) | CA2562142C (zh) |
| ES (2) | ES2244324B1 (zh) |
| MX (1) | MXPA06010833A (zh) |
| NO (1) | NO336582B1 (zh) |
| PA (1) | PA8627401A1 (zh) |
| PE (1) | PE20060015A1 (zh) |
| PL (1) | PL1732517T3 (zh) |
| PT (1) | PT1732517T (zh) |
| RU (2) | RU2006137671A (zh) |
| TW (1) | TWI351957B (zh) |
| UY (1) | UY28809A1 (zh) |
| WO (1) | WO2005092291A1 (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11666587B2 (en) * | 2014-12-12 | 2023-06-06 | Ceva Sante Animale | Veterinary composition comprising torasemide for the treatment of pulmonary edema associated with heart failure in domestic animals |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10596119B1 (en) * | 2018-11-08 | 2020-03-24 | Sarfez Pharmaceuticals, Inc. | Methods of treatment comprising torsemide |
| EP3065718A4 (en) * | 2013-10-06 | 2017-07-12 | Sarfez Pharmaceuticals, Inc. | Controlled-release formulations comprising torsemide |
| US10463622B2 (en) * | 2013-10-06 | 2019-11-05 | Sarfez Pharmaceuticals, Inc. | Treatments and formulations comprising Torsemide |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1378448A (zh) * | 1999-08-11 | 2002-11-06 | 特瓦制药工业有限公司 | 多晶型托拉塞米 |
| CN1505512A (zh) * | 2000-02-17 | 2004-06-16 | ������ҩ��ҵ����˾ | 包含托塞米变型ⅱ的稳定药物制剂 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3305935C2 (de) * | 1983-02-21 | 1985-05-30 | Medice Chem.-Pharm. Fabrik Pütter GmbH & Co KG, 5860 Iserlohn | Kaliumneutrales Saluretikum mit antihypertensiver Wirkung |
| DE3529529A1 (de) * | 1985-08-17 | 1987-02-19 | Boehringer Mannheim Gmbh | Verfahren zur herstellung einer stabilen modifikation von torasemid |
| GB8601204D0 (en) * | 1986-01-18 | 1986-02-19 | Boots Co Plc | Therapeutic agents |
| JP3586471B2 (ja) * | 1991-06-25 | 2004-11-10 | 三菱ウェルファーマ株式会社 | トラセミド含有医薬組成物 |
| DE19637082A1 (de) * | 1996-09-12 | 1998-03-19 | Boehringer Mannheim Gmbh | Schnellzerfallende Pellets |
| GB9816899D0 (en) * | 1998-08-05 | 1998-09-30 | Boots Co Plc | Therapeutic agents |
| DE10013289A1 (de) * | 2000-03-17 | 2001-09-20 | Knoll Ag | Torasemid enthaltende pharmazeutische Zubereitungen |
| US20030119882A1 (en) * | 2001-10-22 | 2003-06-26 | Markus Maegerlein | Solid pharmaceutical composition containing torasemide |
| US20030152622A1 (en) * | 2001-10-25 | 2003-08-14 | Jenny Louie-Helm | Formulation of an erodible, gastric retentive oral diuretic |
| US20030091630A1 (en) * | 2001-10-25 | 2003-05-15 | Jenny Louie-Helm | Formulation of an erodible, gastric retentive oral dosage form using in vitro disintegration test data |
| US20030104052A1 (en) * | 2001-10-25 | 2003-06-05 | Bret Berner | Gastric retentive oral dosage form with restricted drug release in the lower gastrointestinal tract |
| US6863901B2 (en) * | 2001-11-30 | 2005-03-08 | Collegium Pharmaceutical, Inc. | Pharmaceutical composition for compressed annular tablet with molded triturate tablet for both intraoral and oral administration |
| HRP20020124A2 (en) * | 2002-02-11 | 2003-10-31 | Pliva D D | Sustained/controlled release solid formulation as a novel drug delivery system with reduced risk of dose dumping |
| AU2004299077A1 (en) * | 2003-12-12 | 2005-06-30 | Penwest Pharmaceuticals Co. | Sustained release torsemide dosage forms |
-
2004
- 2004-03-25 ES ES200400740A patent/ES2244324B1/es not_active Expired - Lifetime
-
2005
- 2005-03-09 PE PE2005000267A patent/PE20060015A1/es active IP Right Grant
- 2005-03-14 UY UY28809A patent/UY28809A1/es unknown
- 2005-03-16 AR ARP050101017A patent/AR048432A1/es not_active Application Discontinuation
- 2005-03-18 TW TW094108282A patent/TWI351957B/zh not_active IP Right Cessation
- 2005-03-23 JP JP2007504420A patent/JP4871258B2/ja not_active Expired - Fee Related
- 2005-03-23 CN CN2005800093895A patent/CN1946379B/zh not_active Expired - Fee Related
- 2005-03-23 PL PL05717133T patent/PL1732517T3/pl unknown
- 2005-03-23 EP EP05717133.2A patent/EP1732517B1/en active Active
- 2005-03-23 PT PT57171332T patent/PT1732517T/pt unknown
- 2005-03-23 ES ES05717133.2T patent/ES2632354T3/es active Active
- 2005-03-23 US US10/594,004 patent/US20080187585A1/en not_active Abandoned
- 2005-03-23 RU RU2006137671/15A patent/RU2006137671A/ru unknown
- 2005-03-23 WO PCT/EP2005/051340 patent/WO2005092291A1/en active Application Filing
- 2005-03-23 BR BRPI0509165-9A patent/BRPI0509165A/pt not_active Application Discontinuation
- 2005-03-23 MX MXPA06010833A patent/MXPA06010833A/es active IP Right Grant
- 2005-03-23 CA CA2562142A patent/CA2562142C/en active Active
- 2005-03-23 KR KR1020067021596A patent/KR101203763B1/ko active IP Right Grant
- 2005-03-23 AU AU2005227095A patent/AU2005227095B2/en not_active Ceased
- 2005-03-24 PA PA20058627401A patent/PA8627401A1/es unknown
-
2006
- 2006-10-24 NO NO20064834A patent/NO336582B1/no not_active IP Right Cessation
-
2010
- 2010-11-03 RU RU2010145009/15A patent/RU2449778C1/ru active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1378448A (zh) * | 1999-08-11 | 2002-11-06 | 特瓦制药工业有限公司 | 多晶型托拉塞米 |
| CN1505512A (zh) * | 2000-02-17 | 2004-06-16 | ������ҩ��ҵ����˾ | 包含托塞米变型ⅱ的稳定药物制剂 |
Non-Patent Citations (17)
| Title |
|---|
| 第0016段 |
| 第0018段 |
| 第0022段 |
| 第0027段 |
| 第0033段 |
| 第0035段 |
| 第0037段 |
| 第0038段 |
| 第0039－0042段 |
| 第0040段. |
| 第0051－0064段. |
| 第11页第1行至第17页第25行 |
| 第21页第31行 |
| 第24页第16－34行 |
| 第26页第25行至第27页第35行 |
| 第30页第8行至第32页第17行. |
| 第8页第10－14行 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11666587B2 (en) * | 2014-12-12 | 2023-06-06 | Ceva Sante Animale | Veterinary composition comprising torasemide for the treatment of pulmonary edema associated with heart failure in domestic animals |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2005227095B2 (en) | 2010-10-28 |
| CA2562142A1 (en) | 2005-10-06 |
| BRPI0509165A (pt) | 2007-09-11 |
| US20080187585A1 (en) | 2008-08-07 |
| UY28809A1 (es) | 2005-07-29 |
| TWI351957B (en) | 2011-11-11 |
| PL1732517T3 (pl) | 2017-09-29 |
| KR101203763B1 (ko) | 2012-11-23 |
| AU2005227095A1 (en) | 2005-10-06 |
| PT1732517T (pt) | 2017-08-03 |
| WO2005092291A1 (en) | 2005-10-06 |
| TW200531693A (en) | 2005-10-01 |
| PE20060015A1 (es) | 2006-02-02 |
| ES2244324B1 (es) | 2006-11-16 |
| ES2632354T3 (es) | 2017-09-12 |
| AR048432A1 (es) | 2006-04-26 |
| JP2007530510A (ja) | 2007-11-01 |
| RU2006137671A (ru) | 2008-04-27 |
| JP4871258B2 (ja) | 2012-02-08 |
| RU2449778C1 (ru) | 2012-05-10 |
| NO20064834L (no) | 2006-12-07 |
| CN1946379A (zh) | 2007-04-11 |
| KR20060130756A (ko) | 2006-12-19 |
| NO336582B1 (no) | 2015-09-28 |
| ES2244324A1 (es) | 2005-12-01 |
| EP1732517B1 (en) | 2017-05-03 |
| CA2562142C (en) | 2012-06-05 |
| MXPA06010833A (es) | 2006-12-15 |
| EP1732517A1 (en) | 2006-12-20 |
| PA8627401A1 (es) | 2005-11-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1140034B1 (en) | Controlled release formulation of divalproex sodium | |
| US6528091B1 (en) | Controlled release formulation of divalproex sodium | |
| EP1646374A1 (en) | Extended-release tablets of metformin | |
| CN102091051B (zh) | 一种别嘌醇双释放制剂及其制备方法 | |
| CN102657629A (zh) | 替卡格雷缓释片系统及其制备方法 | |
| CN110037994B (zh) | 一种布洛芬速释缓释双层片及其制备方法 | |
| CN1946379B (zh) | 含有托拉塞米和基质成型聚合物的延长释放组合物 | |
| CN104606163A (zh) | 用于持续释放去氧肾上腺素的药用组合物 | |
| CN101416947A (zh) | 复方α-酮酸咀嚼片及制备方法 | |
| US6150410A (en) | pH independent extended release pharmaceutical formulation | |
| CN100525760C (zh) | 盐酸度洛西汀缓释药物 | |
| WO2000045793A1 (en) | Ph independent extended release pharmaceutical formulation | |
| WO2013189305A1 (zh) | 缬沙坦氨氯地平复方固体制剂及其制备方法 | |
| WO2001087228A2 (en) | Sustained release pharmaceutical composition containing glipizide and method for producing same | |
| CN101953833A (zh) | 含苯甲酸利扎曲普坦缓控释剂型、其制备方法和用途 | |
| CN102349876A (zh) | 一种治疗胃溃疡和十二指肠溃疡的药物及其配制方法 | |
| WO1985004099A1 (en) | Sustained release oral dosage form for naproxyn | |
| CN111481554B (zh) | 含氨氯地平和叶酸的片剂及其制备方法 | |
| CN101152187A (zh) | 依普利酮药物组合物 | |
| Ostwal et al. | Development and evaluation for tablet-in capsule of nefedipine and atenolol | |
| CN100581549C (zh) | 一种含氢氯噻嗪的缓释制剂及其制备方法 | |
| CN102335153A (zh) | 一种阿魏酸哌嗪缓释片及其制备方法 | |
| CN101683330A (zh) | 一种含有曲尼司特和沙丁胺醇的口服复方药物制剂 | |
| CA2469327A1 (en) | Propafenone hydrochloride capsules containing microtablets | |
| AU2004210543A1 (en) | Controlled release formulation of divalproex sodium |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120516 |