CN1069408A - 球状药用制剂 - Google Patents

球状药用制剂 Download PDF

Info

Publication number
CN1069408A
CN1069408A CN92105698A CN92105698A CN1069408A CN 1069408 A CN1069408 A CN 1069408A CN 92105698 A CN92105698 A CN 92105698A CN 92105698 A CN92105698 A CN 92105698A CN 1069408 A CN1069408 A CN 1069408A
Authority
CN
China
Prior art keywords
controlled release
composition according
spherical core
pharmaceutically acceptable
weight
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN92105698A
Other languages
English (en)
Other versions
CN1052398C (zh
Inventor
I·R·巴克斯顿
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
European Celtic
Euro Celtique SA
Original Assignee
European Celtic
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from GB919117361A external-priority patent/GB9117361D0/en
Priority claimed from GB919122967A external-priority patent/GB9122967D0/en
Application filed by European Celtic filed Critical European Celtic
Publication of CN1069408A publication Critical patent/CN1069408A/zh
Application granted granted Critical
Publication of CN1052398C publication Critical patent/CN1052398C/zh
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

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
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/501—Inorganic compounds
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5015—Organic compounds, e.g. fats, sugars
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
    • A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Steroid Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Compounds Of Unknown Constitution (AREA)

Abstract

一种受控释放组合物，包括由硫氮酮或其药学 上可接受的盐和可选的成球剂组成的球状核，所述核 被一种受控释放材料涂覆。如果加入成球剂的话，最 好选用微晶纤维素。乙基纤维素是优选的受控释放 涂层。受控释放涂层最好包含增塑剂、表面活性剂和 胶粘改性剂。

Description

本发明涉及一种受控释放制剂及其制备方法，尤其涉及含硫氮
Figure 921056982_IMG6
酮的控制释放制剂。
硫氮
Figure 921056982_IMG7
酮是一种钙拮抗剂，可用来治疗心脏病，例如心胶病和高血压。
本发明的目的是提供一种受控释放硫氮
Figure 921056982_IMG8
酮制剂，适于每日一次给药，治疗高血压和心绞痛。
因此，本发明提供包含球状核的受控释放制剂，该核由硫氮
Figure 921056982_IMG9
酮或其药学上可接受的盐组成，还可含有成球剂，并覆有受控释放层。
本发明所用的适当的药学上可接受的盐包括药学上可接受的酸加成盐。特别优选盐酸盐。
本发明的受控释放药用组合物能够在较长时间内缓慢释放药物，并且在该时间内延长药物作用时间以达到常规药物传送的效果。
“球状”一词是药学领域的常用词，它是指直径为0.1mm～2.5mm;尤其是0.5mm～2mm的球状粒子。
本发明球状核最好含40%～98%，含60%～85%更好，尤其含70%～85%（重量）硫氮
Figure 921056982_IMG10
酮或其药学上可接受的盐。
成球剂可以是任何适当的药学上可接受的材料。它可以与活性成分一起成球以形成球状核。优选的成球剂是微晶纤维素，所用的微晶纤维素可以是，例如阿维塞尔PH107或阿维塞尔PH102（商品名，FMC公司）。一般来说，当存在成球剂时，它占球状核的1%～60%（重量），最好药15%～40%（重量）。
球状核还可含有其它药学上可接受赋形剂和稀释剂。使之易于成球，例如用糖（如蔗糖、右旋糖、麦芽糖或乳糖）或糖醇（例如甘露醇、木糖醇或山梨糖醇）。在球状核中还可含有着色剂。
球状核最好是涂覆允许硫氮
Figure 921056982_IMG11
酮在水性介质中控制速率释放的膜，适宜的涂膜材料可包括水不溶蜡和聚合物，例如聚甲基丙烯酸酯（例如商标为Eudragit的聚合物）或优选水不溶纤维素，特别是乙基纤维素。这膜涂层还可含水溶性聚合物，例如聚乙烯吡咯烷酮或最好是水溶性纤维素，例如羟丙基甲基纤维素和羟丙基纤维素。应当理解，水不溶材料与水溶性材料的比率取决于所要求的释放速度和所选村料的溶解度，水溶性聚合物与水不溶聚合物的比率以1∶20至1∶2为佳。受控释放涂层优选包括一种或多种本领域的常规增塑剂，例如酞酸二乙酯，但最好是癸二酸二丁酯;表面活性剂，例如山梨聚糖三油酸酯、山梨聚糖单月桂酸酯或优选多乙氧基醚80（商标为Tween80）和胶粘改性剂，例如滑石粉或优选胶质无水硅石。
当存在增塑剂时，其含量将取决于所选的特定增塑剂，一般，增塑剂的量为受控释放膜涂层的1%至25%（重量）。当存在表面活性剂时，其适宜存在量为受控膜涂层的1%至25%（重量）当存在胶粘改性剂时，其存在量也以受控释放膜涂层的1%至25%（重量）为宜。
优选的受控释放膜涂层包括50%至95%乙基纤维素，5%至15%胶质无水硅石，5%至15%癸二酸二丁酯和5%至15%多乙氧基醚80（商标为Tween  80）。
采用传统涂覆方法例如流化床或槽式涂覆，可在含硫氮
Figure 921056982_IMG12
酮的球状核的表面形成受控释放涂膜层。该涂层材料可应用溶液或悬浮液，适宜的溶剂系统包括水、二氯甲烷、乙醇、甲醇、异丙醇和丙酮及其混合物。涂覆溶液或悬浮液优选含2%至60%（重量）、最好含2%至20%（重量）涂覆材料。
受控释放涂覆材料的用量取决于所要求的释放速率，但是一般为受控释放涂覆球体的1%至25%（重量），最好为2%至8%（重量）。
本发明含硫氮
Figure 921056982_IMG13
酮球体的制备方法包括以下步骤：
（a）将包括硫氮
Figure 921056982_IMG14
酮或其药学上可接受的盐、水和可选的成球剂的混合物成粒;
（b）挤压成粒混合物，得到挤出物;
（c）将挤出物成球，直至形成球状核;
（d）干燥球状核;并且
（e）膜涂覆球状核。
采用传统制药技术可将本发明组合物填充制成胶囊或压制成片剂。
本发明组合物的可适当地每日一次给药。一般每日一次给药，剂型中硫氮）酮或其药学上可接受的盐（优选硫氮
Figure 921056982_IMG15
酮盐酸盐）的含量为120mg～300mg。
为了更好地理解本发明，给出下述实施例，仅为说明而已。
实施例1
制备了具有下述配方的胶囊
硫氮
Figure 921056982_IMG16
酮球状核
材料  毫克
硫氮
Figure 921056982_IMG17
酮盐酸盐U.S.P 120
微晶纤维素E.P（Avicel  PH  101）  30.0
蒸馏水E.P  适量
150
受控释放膜涂层
材料  毫克
硫氮
Figure 921056982_IMG18
酮盐酸盐球状核 150
乙基纤维素N10  U.S.N.F  7.38
胶质无水硅石E.P.（Aerosil  130）  0.988
癸二酸二丁酯U.S.N.F.  0.742
多乙氧基醚80  E.P.（Tween80）  0.791
二氯甲烷BS  1994  适量
甲醇B.P.1973  适量
160
胶囊制剂  mg
硫氮
Figure 921056982_IMG19
酮受控释放球状体 160
硬酯酸镁  EP  0.480
明胶囊壳3号（Size  3）
采用高剪切混合器混合硫氮
Figure 921056982_IMG20
酮和微晶纤维素，该混合是湿式成粒，挤压后得到挤出物，成粒并置于流化床干燥器中干燥，所得球体过筛，得到粒径为0.85-1.7毫米。
将受控释放涂膜成分分散在二氯甲烷/甲醇溶剂体系中，应用到流化床涂敷器内的硫氮
Figure 921056982_IMG21
酮球状核上，得到的涂膜球体过筛，然后，在流化床涂覆器中，将含硫氮
Figure 921056982_IMG22
酮受控释放球体用双氢氯噻嗪和羟丙基甲基纤维素的分散体涂膜。
通过EP篮式装置（100转/分），用PH4.5EP磷酸盐缓冲液测定所得产品的溶解度。所得结果如下：
硫氮 酮溶解度
时间（小时） 硫氮 酮受控释放
                  球状体
1  9
2  23
3  37
4  48
5  57
6  63
8  72
10  77
12  81
15  86
20  90

Claims (12)

1、一种受控释放组合物，包括由硫氮
Figure 921056982_IMG2
酮或其药学上可接受的盐和可选的成球剂组成的球状核，所述核被一种受控释放材料涂覆。
2、按照权利要求1的组合物，其中，球状核包含40%～98%（重量）的硫氮
Figure 921056982_IMG3
酮或其药学上可接受的盐。
3、按照权利要求2的组合物，其中，球状核包含70%～85%（重量）的硫氮 酮或其药学上可接受的盐。
4、接照权利要求1至3的组合物，其中，成球剂的含量为球状核重量的15%～40%。
5、按照权利要求4的组合物，其中，成球剂包括微晶纤维素。
6、按照权利要求1至5任一项的组合物，其中，受控释放涂覆材料包括水不溶性聚合物。
7、按照权利要求6的组合物，其中，涂覆材料包括乙基纤维素。
8、按照权利要求1至7任一项的组合物，其中，受控释放涂覆材料还包括一种或多种增塑剂、表面活性剂和胶粘改性剂。
9、按照权利要求8的组合物，其中，受控释放涂层包括50%～95%乙基纤维素、5%～15%胶状无水硅石、5%～15%癸二酸二丁酯和5%～15%多乙氧基醚80。
10、按照权利要求1至9任一项的组合物，其中，受控释放涂覆材料的用量为组合物重量的2%～8%。
11、一种胶囊，它包含权利要求1至10任一项的受控释放涂覆的球状核。
12、一种制备权利要求1至10任一项的组合物的方法，包括：
（a）将包括硫氮
Figure 921056982_IMG5
酮或其在药学上可接受盐、水和可选的成球剂的混合物成粒;
（b）挤压成粒混合物，得到挤出物;
（c）将挤出物成球，直至形成球状核;
（d）干燥球状核;并且
（e）用受控释放材料涂覆球状核。
CN92105698A 1991-08-12 1992-08-12 球状药用制剂 Expired - Lifetime CN1052398C (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB919117361A GB9117361D0 (en) 1991-08-12 1991-08-12 Oral dosage form
GB9117361.7 1991-08-12
GB9122967.4 1991-10-29
GB919122967A GB9122967D0 (en) 1991-10-29 1991-10-29 Pharmaceutical composition

Publications (2)

Publication Number Publication Date
CN1069408A true CN1069408A (zh) 1993-03-03
CN1052398C CN1052398C (zh) 2000-05-17

Family

ID=26299395

Family Applications (1)

Application Number Title Priority Date Filing Date
CN92105698A Expired - Lifetime CN1052398C (zh) 1991-08-12 1992-08-12 球状药用制剂

Country Status (14)

Country Link
US (2) US5670172A (zh)
EP (1) EP0527637B1 (zh)
JP (1) JP3019235B2 (zh)
KR (1) KR100221695B1 (zh)
CN (1) CN1052398C (zh)
AT (1) ATE165513T1 (zh)
AU (1) AU651715B2 (zh)
CA (1) CA2075356A1 (zh)
DE (1) DE69225278D1 (zh)
ES (1) ES2115643T3 (zh)
FI (1) FI923582L (zh)
IL (1) IL102778A (zh)
NO (1) NO304406B1 (zh)
PH (1) PH31288A (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100411611C (zh) * 2002-04-05 2008-08-20 欧洲凯尔蒂克公司 用于持续,不变且独立释放活性化合物的基质
CN1489455B (zh) * 2000-10-13 2010-05-26 欧洲凯尔特公司 延释药物制剂

Families Citing this family (93)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5266331A (en) * 1991-11-27 1993-11-30 Euroceltique, S.A. Controlled release oxycodone compositions
US5681585A (en) * 1991-12-24 1997-10-28 Euro-Celtique, S.A. Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer
US20080075781A1 (en) * 1992-11-25 2008-03-27 Purdue Pharma Lp Controlled release oxycodone compositions
FR2702160B1 (fr) * 1993-03-02 1995-06-02 Biovecteurs As Vecteurs particulaires synthétiques et procédé de préparation.
SE9301220D0 (sv) * 1993-04-14 1993-04-14 Kabi Pharmacia Ab Manufacturing matrices
US20070275062A1 (en) * 1993-06-18 2007-11-29 Benjamin Oshlack Controlled release oxycodone compositions
IL110014A (en) * 1993-07-01 1999-11-30 Euro Celtique Sa Solid controlled-release oral dosage forms of opioid analgesics
US7740881B1 (en) 1993-07-01 2010-06-22 Purdue Pharma Lp Method of treating humans with opioid formulations having extended controlled release
US5834024A (en) * 1995-01-05 1998-11-10 Fh Faulding & Co. Limited Controlled absorption diltiazem pharmaceutical formulation
GB9519363D0 (en) 1995-09-22 1995-11-22 Euro Celtique Sa Pharmaceutical formulation
US5914134A (en) * 1997-01-27 1999-06-22 Wockhardt Europe Limited Process for the pulsatile delivery of diltiazem HCL and product produced thereby
US7060734B1 (en) 1997-09-09 2006-06-13 Alza Corporation Pharmaceutical coating composition and method of use
PT1014951E (pt) * 1997-09-09 2005-03-31 Alza Corp Composicao de revestimento farmaceutica e metodo para a sua utilizacao
US5891845A (en) * 1997-11-21 1999-04-06 Fuisz Technologies Ltd. Drug delivery systems utilizing liquid crystal structures
JP2001526228A (ja) 1997-12-22 2001-12-18 ユーロ−セルティーク，エス．エイ． オピオイド作動薬／拮抗薬の併用
CA2314896C (en) * 1997-12-22 2005-09-13 Euro-Celtique, S.A. A method of preventing abuse of opioid dosage forms
US6524620B2 (en) 1998-07-20 2003-02-25 Andrx Pharmaceuticals, Inc. Diltiazem controlled release formulation and method of manufacture
US6806294B2 (en) 1998-10-15 2004-10-19 Euro-Celtique S.A. Opioid analgesic
US6432448B1 (en) 1999-02-08 2002-08-13 Fmc Corporation Edible coating composition
US6723342B1 (en) 1999-02-08 2004-04-20 Fmc Corporation Edible coating composition
US6410255B1 (en) * 1999-05-05 2002-06-25 Aurora Biosciences Corporation Optical probes and assays
DE60043400D1 (de) 1999-05-14 2010-01-07 Nereus Pharmaceuticals Inc Interleukin-1 und Tumornekrosefaktor-alpha Modulatoren,Synthese dieser Modulatoren und Methoden zur Anwendung dieser Modulatoren
GB9913979D0 (en) 1999-06-17 1999-08-18 Univ Wales Medicine Spheroid preparation
US10179130B2 (en) 1999-10-29 2019-01-15 Purdue Pharma L.P. Controlled release hydrocodone formulations
US6500462B1 (en) 1999-10-29 2002-12-31 Fmc Corporation Edible MCC/PGA coating composition
KR100889069B1 (ko) 1999-10-29 2009-03-17 유로-셀티크 소시에떼 아노뉨 서방성 하이드로코돈 제형
US20060153914A1 (en) * 1999-12-10 2006-07-13 Biovail Laboratories International S.R.L. Chronotherapeutic diltiazem formulations and the administration thereof
US7108866B1 (en) 1999-12-10 2006-09-19 Biovall Laboratories International Srl Chronotherapeutic diltiazem formulations and the administration thereof
HU229705B1 (en) 2000-02-08 2014-05-28 Euro Celtique Sa Tamper-resistant oral opioid agonist formulations
ATE439441T1 (de) 2000-02-23 2009-08-15 Life Technologies Corp Veränderte, fluoreszierende proteine
US6852031B1 (en) * 2000-11-22 2005-02-08 Igt EZ pay smart card and tickets system
US6635277B2 (en) 2000-04-12 2003-10-21 Wockhardt Limited Composition for pulsatile delivery of diltiazem and process of manufacture
AU2738302A (en) 2000-10-30 2002-05-15 Euro Celtique Sa Controlled release hydrocodone formulations
JP4395549B2 (ja) * 2000-11-16 2010-01-13 ザ レジェンツ オブ ザ ユニヴァースティ オブ カリフォルニア 薬物及び発酵生成物の発見のための海洋放線菌分類群
BR0115585A (pt) 2000-11-28 2005-12-13 Fmc Corp Composições de revestimento de pronta liberação, endurecìvel, comestìvel, seca e, úmida, forma de dosagem sólida, e, método para revestir uma forma de dosagem sólida farmacêutica ou veterinária, confeito, semente, ração animal, fertilizante, comprimido de pesticida ou alimento
US6932861B2 (en) 2000-11-28 2005-08-23 Fmc Corporation Edible PGA coating composition
US20110104214A1 (en) 2004-04-15 2011-05-05 Purdue Pharma L.P. Once-a-day oxycodone formulations
UA81224C2 (uk) * 2001-05-02 2007-12-25 Euro Celtic S A Дозована форма оксикодону та її застосування
CN1525851A (zh) 2001-05-11 2004-09-01 ������ҩ�����޹�˾ 抗滥用阿片样物质控释剂型
SI1416842T1 (sl) 2001-07-18 2009-06-30 Euro Celtique Sa Farmacevtske kombinacije oksikodona in naloksona
ATE431738T1 (de) 2001-08-06 2009-06-15 Euro Celtique Sa Opioid-agonist-formulierungen mit freisetzbarem und sequestriertem antagonist
US20030044458A1 (en) 2001-08-06 2003-03-06 Curtis Wright Oral dosage form comprising a therapeutic agent and an adverse-effect agent
AU2002324624A1 (en) 2001-08-06 2003-02-24 Euro-Celtique S.A. Sequestered antagonist formulations
US20030181488A1 (en) * 2002-03-07 2003-09-25 Boehringer Ingelheim Pharma Gmbh & Co. Kg Administration form for the oral application of 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionic acid ethyl ester and the salts thereof
US7176232B2 (en) 2002-06-24 2007-02-13 The Regents Of The University Of California Salinosporamides and methods for use thereof
US7815934B2 (en) 2002-09-20 2010-10-19 Alpharma Pharmaceuticals, Llc Sequestering subunit and related compositions and methods
AU2003296908A1 (en) * 2002-09-27 2004-05-04 Nereus Pharmaceuticals, Inc. Macrocyclic lactams
US20040202717A1 (en) 2003-04-08 2004-10-14 Mehta Atul M. Abuse-resistant oral dosage forms and method of use thereof
US20040208932A1 (en) * 2003-04-17 2004-10-21 Ramachandran Thembalath Stabilized paroxetine hydrochloride formulation
MY135852A (en) 2003-04-21 2008-07-31 Euro Celtique Sa Pharmaceutical products
KR20060026052A (ko) * 2003-06-20 2006-03-22 니리어스 파마슈티컬즈, 인코퍼레이션 암, 염증 및 감염성 질환의 치료를 위한 [3.2.0]헤테로사이클릭 화합물 및 그 유사체의 사용방법
EP2441767B1 (en) * 2003-06-20 2015-06-10 The Regents of The University of California Salinosporamides and methods for use thereof
US7619059B2 (en) * 2003-07-29 2009-11-17 Life Technologies Corporation Bimolecular optical probes
CA2445420A1 (en) * 2003-07-29 2005-01-29 Invitrogen Corporation Kinase and phosphatase assays
US7727752B2 (en) 2003-07-29 2010-06-01 Life Technologies Corporation Kinase and phosphatase assays
US20050064485A1 (en) * 2003-09-12 2005-03-24 Kurt Vogel Multiplex binding and activity assays
BRPI0506535A (pt) * 2004-01-23 2007-02-27 Nereus Pharmaceuticals Inc pirroles bis-indole úteis como agentes anti-microbiais
BRPI0509824A (pt) 2004-04-30 2007-10-09 Nereus Pharmaceuticals Inc compostos heterocìclicos [3.2.0] e métodos de uso dos mesmos
US7579371B2 (en) 2004-04-30 2009-08-25 Nereus Pharmaceuticals, Inc. Methods of using [3.2.0] heterocyclic compounds and analogs thereof
EP1604666A1 (en) 2004-06-08 2005-12-14 Euro-Celtique S.A. Opioids for the treatment of the Chronic Obstructive Pulmonary Disease (COPD)
CA2588295C (en) 2004-11-23 2013-10-22 Adamas Pharma, Llc Method and composition for administering an nmda receptor antagonist to a subject
US7619007B2 (en) 2004-11-23 2009-11-17 Adamas Pharmaceuticals, Inc. Method and composition for administering an NMDA receptor antagonist to a subject
EP2623099A1 (en) 2004-11-24 2013-08-07 Neuromolecular Pharmaceuticals, Inc Composition and method for treating neurological disease
SG157365A1 (en) * 2004-12-03 2009-12-29 Dana Farber Cancer Inst Inc Compositions and methods for treating neoplastic diseases
EP1702558A1 (en) 2005-02-28 2006-09-20 Euro-Celtique S.A. Method and device for the assessment of bowel function
WO2006103671A1 (en) * 2005-03-31 2006-10-05 Rafael Armament Development Authority Ltd. Apparatus for treating particles and liquids by ultrasound
ATE481096T1 (de) 2005-04-06 2010-10-15 Adamas Pharmaceuticals Inc Verfahren und zusammensetzungen zur behandlung von zns-erkrankungen
EP2311795A3 (en) 2005-07-21 2011-12-28 Nereus Pharmaceuticals, Inc. Interleukin-1 and tumor necrosis factor-alpha modulators; syntheses of such modulators and methods of using such modulators
SI2719378T1 (sl) 2006-06-19 2016-11-30 Alpharma Pharmaceuticals Llc Farmacevtski sestavki
US20080075768A1 (en) * 2006-07-21 2008-03-27 Vaughn Jason M Hydrophobic opioid abuse deterrent delivery system using opioid antagonists
EP1920767A1 (en) * 2006-11-09 2008-05-14 Abbott GmbH & Co. KG Melt-processed imatinib dosage form
WO2008095195A2 (en) * 2007-02-02 2008-08-07 Nereus Pharmaceuticals, Inc. Lyophilized formulations of salinosporamide a
US20090017167A1 (en) * 2007-07-11 2009-01-15 Herbalife International Inc. Mixture and beverage made therefrom for protecting cellular hydration
US8394816B2 (en) * 2007-12-07 2013-03-12 Irene Ghobrial Methods of using [3.2.0] heterocyclic compounds and analogs thereof in treating Waldenstrom's Macroglobulinemia
EP2224808A4 (en) * 2007-12-17 2013-11-27 Alpharma Pharmaceuticals Llc PHARMACEUTICAL COMPOSITION
US8623418B2 (en) 2007-12-17 2014-01-07 Alpharma Pharmaceuticals Llc Pharmaceutical composition
US8486448B2 (en) * 2007-12-17 2013-07-16 Paladin Labs Inc. Misuse preventative, controlled release formulation
US20100151014A1 (en) * 2008-12-16 2010-06-17 Alpharma Pharmaceuticals, Llc Pharmaceutical composition
CN102089312A (zh) * 2008-05-12 2011-06-08 尼瑞斯药品公司 作为蛋白酶体抑制剂的Salinosporamide衍生物
RU2478388C2 (ru) * 2008-07-07 2013-04-10 Еуро-Селтик С.А. Фармацевтическая композиция, содержащая опиоидный антагонист, для лечения задержки мочи
MY152279A (en) 2009-03-10 2014-09-15 Euro Celtique Sa Immediate release pharmaceutical compositions comprising oxycodone and naloxone
CA2994873A1 (en) 2009-12-02 2011-06-09 Adamas Pharma, Llc Amantadine compositions and methods of use
CA2835293C (en) * 2011-06-08 2020-08-18 Sti Pharma, Llc Controlled absorption water-soluble pharmaceutically active organic compound formulation for once-daily administration
ITFI20110172A1 (it) * 2011-08-08 2013-02-09 Valpharma Sa Formulazione multiparticolata a rilascio modificato di diltiazem hcl.
US10154971B2 (en) 2013-06-17 2018-12-18 Adamas Pharma, Llc Methods of administering amantadine
US10071089B2 (en) 2013-07-23 2018-09-11 Euro-Celtique S.A. Combination of oxycodone and naloxone for use in treating pain in patients suffering from pain and a disease resulting in intestinal dysbiosis and/or increasing the risk for intestinal bacterial translocation
AU2015312134A1 (en) 2014-09-02 2017-03-23 Bhupinder Singh Deuterated or a non-deuterated molecule and pharmaceutical formulations
IL312208A (en) 2014-10-08 2024-06-01 Pacific Northwest Res Institute Methods and preparations for increasing the potency of antifungal agents
CN109069480A (zh) 2015-12-30 2018-12-21 阿达玛斯医药公司 用于治疗与癫痫相关的病症的方法和组合物
DE102016117163B4 (de) 2016-09-13 2025-02-13 EnBW Energie Baden-Württemberg AG Fahrzeug für eine Vorrichtung zum Abtragen kontaminierter Flächen und Verfahren zum Abtragen kontaminierter Flächen
WO2018200885A1 (en) 2017-04-26 2018-11-01 Neurocentria, Inc. Magnesium compositions and methods of use
CN112533614A (zh) 2018-03-28 2021-03-19 美国康宝莱国际公司 多糖的乙酰化
WO2024173418A1 (en) 2023-02-16 2024-08-22 Infinitum Health, Llc Methods of inhibiting cancer growth and inhibiting viral infections

Family Cites Families (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4456628A (en) * 1981-01-07 1984-06-26 Bauer Kurt H Process for film-coating a particulate solid, and emulsions for conducting the process
DK152744C (da) * 1982-08-13 1988-10-31 Benzon As Alfred Fremgangsmaade til fremstilling af et farmaceutisk peroralt polydepotpraeparat
US4898729A (en) * 1983-12-09 1990-02-06 Euroceltique, S.A. Treatment of hypertension, compounds and compositions for antihypertension and diuresis
US4894240A (en) * 1983-12-22 1990-01-16 Elan Corporation Plc Controlled absorption diltiazem formulation for once-daily administration
US5002776A (en) * 1983-12-22 1991-03-26 Elan Corporation, Plc Controlled absorption diltiazem formulations
US4917899A (en) * 1983-12-22 1990-04-17 Elan Corporation Plc Controlled absorption diltiazem formulation
US5364620A (en) * 1983-12-22 1994-11-15 Elan Corporation, Plc Controlled absorption diltiazem formulation for once daily administration
IE56999B1 (en) * 1983-12-22 1992-03-11 Elan Corp Plc Pharmaceutical formulation
DE3403329A1 (de) * 1984-02-01 1985-08-01 Horst Dr. 4019 Monheim Zerbe Pharmazeutisches produkt in form von pellets mit kontinuierlicher, verzoegerter wirkstoffabgabe
US4643731A (en) * 1985-08-16 1987-02-17 Alza Corporation Means for providing instant agent from agent dispensing system
JPS62103012A (ja) * 1985-10-23 1987-05-13 Eisai Co Ltd 多重顆粒
IT1200217B (it) * 1986-09-30 1989-01-05 Valducci Roberto Membrana per uso farmaceutico ed industriale
DE3709188A1 (de) * 1987-03-20 1988-09-29 Mannesmann Ag Ausgiessrohr fuer metallurgische gefaesse
GB8707421D0 (en) * 1987-03-27 1987-04-29 Wellcome Found Pharmaceutical formulations
US4808413A (en) * 1987-04-28 1989-02-28 E. R. Squibb & Sons, Inc. Pharmaceutical compositions in the form of beadlets and method
CA1323833C (en) * 1987-04-28 1993-11-02 Yatindra M. Joshi Pharmaceutical compositions in the form of beadlets and method
BE1000794A4 (nl) * 1987-07-30 1989-04-04 Schelde Delta Bv Met Beperkte Werkwijze voor het bij chemische processen immobiliseren van komponenten in een fluidumstroom, en inrichtingen die deze werkwijze toepassen.
US4814181A (en) * 1987-09-03 1989-03-21 Alza Corporation Dosage form comprising fast agent delivery followed by slow agent delivery
US5219621A (en) * 1987-10-16 1993-06-15 Elan Corporation, Plc Methods of treatment with diltiazem formulations
DE3856555T2 (de) * 1987-10-16 2004-04-29 Elan Corp. Plc Diltiazem-Zusammensetzungen mit kontrollierter Wirkstoffabsorption
IL88083A (en) * 1987-11-06 1992-11-15 Tanabe Seiyaku Co Controlled release pharmaceutical dosage form and its preparation
DE3739779A1 (de) * 1987-11-24 1989-06-08 Beiersdorf Ag Pharmazeutische praeparate
FR2623714B1 (fr) * 1987-11-26 1990-04-20 Ethypharm Sa Forme a liberation prolongee du diltiazem, et son medicament ainsi obtenu
FR2624732B1 (fr) * 1987-12-21 1991-02-15 Synthelabo Formulation pharmaceutique a liberation prolongee
JP2643222B2 (ja) * 1988-02-03 1997-08-20 エーザイ株式会社 多重層顆粒
GB8805695D0 (en) * 1988-03-10 1988-04-07 Nycomed As Enteric coated spheroidal granules
FI101344B1 (fi) * 1988-03-31 1998-06-15 Tanabe Seiyaku Co Menetelmä valmistaa valmiste, josta kontrolloidusti vapautuu farmaseuttisesti aktiivista ainetta
FR2630647B1 (fr) * 1988-04-27 1991-08-16 Sanofi Sa Microbilles de diltiazem, leur procede de fabrication et compositions pharmaceutiques a liberation prolongee les contenant
ZA899071B (en) * 1988-11-30 1990-08-29 Schering Corp Sustained release diltiazem formulation
SE506179C2 (sv) * 1989-01-23 1997-11-17 Ciba Geigy Ag Farmaceutisk lågkomposition av benazepril och ett tiaziddiuretikum
SE8902699D0 (sv) * 1989-08-09 1989-08-09 Lejus Medical Ab Diltiazem containing pharmaceutical compositios
JPH0674206B2 (ja) * 1989-12-28 1994-09-21 田辺製薬株式会社 放出制御型製剤およびその製法
IT1241417B (it) * 1990-03-06 1994-01-14 Vectorpharma Int Composizioni terapeutiche a rilascio controllato di farmaci supportatisu polimeri reticolati e rivestiti con film polimerici,e loro processodi preparazione
US5286497A (en) * 1991-05-20 1994-02-15 Carderm Capital L.P. Diltiazem formulation
ZA923474B (en) * 1991-05-20 1993-01-27 Marion Merrell Dow Inc Diltiazem formulation

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1489455B (zh) * 2000-10-13 2010-05-26 欧洲凯尔特公司 延释药物制剂
CN100411611C (zh) * 2002-04-05 2008-08-20 欧洲凯尔蒂克公司 用于持续,不变且独立释放活性化合物的基质

Also Published As

Publication number Publication date
EP0527637B1 (en) 1998-04-29
AU651715B2 (en) 1994-07-28
NO923128L (no) 1993-02-15
ES2115643T3 (es) 1998-07-01
IL102778A0 (en) 1993-01-31
DE69225278D1 (de) 1998-06-04
PH31288A (en) 1998-07-06
US5670172A (en) 1997-09-23
NO304406B1 (no) 1998-12-14
JPH05201867A (ja) 1993-08-10
FI923582A0 (fi) 1992-08-11
FI923582A7 (fi) 1993-02-13
NO923128D0 (no) 1992-08-11
AU2088092A (en) 1993-02-18
EP0527637A1 (en) 1993-02-17
IL102778A (en) 1999-05-09
CA2075356A1 (en) 1993-02-13
US5601845A (en) 1997-02-11
CN1052398C (zh) 2000-05-17
ATE165513T1 (de) 1998-05-15
KR930003906A (ko) 1993-03-22
JP3019235B2 (ja) 2000-03-13
KR100221695B1 (ko) 1999-09-15
FI923582L (fi) 1993-02-13

Similar Documents

Publication Publication Date Title
CN1069408A (zh) 球状药用制剂
JP6169411B2 (ja) ゾニサミドの徐放性製剤
AU760006B2 (en) Method for making granules with masked taste and instant release of the active particle
JP3350559B2 (ja) 活性成分を含有する予め成形された微小粒子より製造される機械的に安定でかつ容易に分解し得る錠剤
US8709996B2 (en) Pharmaceutical treatment process using chitosan or derivative thereof
CZ284924B6 (cs) Prostředek s řízeným uvolňováním, který obsahuje morfinovou sůl
JP2001522874A (ja) オメプラゾールの配合物
CN1069191A (zh) 药用组合制剂
CN1202814C (zh) 具有贮存稳定释放模式的控释曲马朵制剂和其制备方法
CN1195984A (zh) 含有达非那新的药物制剂
JP2000212068A (ja) 薬学的有効物質９０重量％まで含有するペレットの製造方法。
JP2001521892A (ja) 持続放出性製剤
CN1744889A (zh) 坦洛新的控释药物组合物
CN1161112C (zh) 含氯雷他定和伪麻黄碱的药物胶囊组合物
EP1653932A1 (en) Modified release compositions for minocycline
CN1882321A (zh) 包含盐酸文拉法辛的小丸
CN1390121A (zh) 硫酸吗啡微粒,其制备方法及含有该物质的组合物
CN1305371A (zh) 程序化和随时间释放的多颗粒药物剂型及其制备方法
CN1303291A (zh) 包含头孢克洛的缓释组合物
ES2516693T3 (es) Esferoides farmacéuticos
CN1232386A (zh) 弱酸药物的结肠运送
GB2258613A (en) Pharmaceutical diltiazem spheroid formulation
WO2005016317A1 (en) Process for manufacture of extended release pellets containing diltiazem hci

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
C15 Extension of patent right duration from 15 to 20 years for appl. with date before 31.12.1992 and still valid on 11.12.2001 (patent law change 1993)
OR01 Other related matters
C17 Cessation of patent right
CX01 Expiry of patent term

Expiration termination date: 20120812

Granted publication date: 20000517