CN1025283C - 生产控制释放产品时用的小珠的制备方法 - Google Patents

生产控制释放产品时用的小珠的制备方法 Download PDF

Info

Publication number
CN1025283C
CN1025283C CN86106651A CN86106651A CN1025283C CN 1025283 C CN1025283 C CN 1025283C CN 86106651 A CN86106651 A CN 86106651A CN 86106651 A CN86106651 A CN 86106651A CN 1025283 C CN1025283 C CN 1025283C
Authority
CN
China
Prior art keywords
grams
active compounds
pharmaceutical active
millimeter
globule
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 - Lifetime
Application number
CN86106651A
Other languages
English (en)
Other versions
CN86106651A (zh
Inventor
拉斯-埃里克.戴维.达尔林德
马茨·奥夫·约翰森
约翰·安德斯·桑德伯格
约翰·艾伯特·削格伦
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.)
Hassle AB
Original Assignee
Hassle AB
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
Application filed by Hassle AB filed Critical Hassle AB
Publication of CN86106651A publication Critical patent/CN86106651A/zh
Application granted granted Critical
Publication of CN1025283C publication Critical patent/CN1025283C/zh
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

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
    • A61K9/2072—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
    • 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
    • A61K9/5078—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 with drug-free core

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

含有若干覆盖有一种或多种药物活性化合物的不溶性的小珠的控制释放制剂，它的制备方法以及在需要控制释放药物活性化合物的治疗中的使用。

Description

本发明涉及具有药物活性化合物的控制释放的新药物制剂，此类制剂的制造方法以及获得药物活性化合物的控制释放的方法。
在医疗各种疾病中，例如在心血管、胃肠道和化疗方面，使所给药物在血中具有恒定的浓度是有好处的。因此需要从药物制剂中有控制地释放药物。
重要的是控制释放的制剂所释放出来的药物量，应能在整个治疗剂量期间维持相当的和稳定的效果。这通常意味着，药物的释放应该有恒定速率以使血液中的所给药物浓度保持稳定，这对于具有小治疗指数，即有效浓度与毒性浓度之间差别很小的药物特别重要。对于当在大的局部浓度存在时具有能引起胃肠道紊乱的潜在危险的局部刺激性药物或对于具有短排除半衰期的药物，药物的延缓和恒定释放也将是重要的。在排除半衰期短的药物中，控制释放的制剂比常规剂量形式给药次数较少，因此患者有较好的顺应性（参看Hayes    R.B.等Clin.Pharm.Therap.（1977年），22卷，125-130页）。
一个药物能通过任何给药途经用控制的方法进行释放，但该类制剂最好要具有某些共同的特征，例如提供有控制的和能重复产生的药物释放并有助于重复的吸收，没有毒性或没有刺激性的成分，并且也适宜于高剂量药物。
对于口服用药物，可以控制释放药物的体系的例子为不溶性基质类型的持续释放片剂，如DurulesR，和渗透活性片剂，即OROSR。OROSR体系在美国专利案号4，036，227中以及由英国Theeuwes F.等在Journal of Clinical Pharmacology（1985年），19卷，695-765页（补充部分）中曾有描述。它的主要部分是药物的片剂核心，核的周围包有钻一小孔的半渗透聚合物膜。联邦德国专利（DE-A-2030501）描述包含无定形二氧化硅的基质类型的制剂。活性化合物通过基质扩散释放出来。上述那些例子是单一单位体系，所有药物集中在一单位内，而本发明是多一单位原理。
从英国专利（GB-A-1542414）一种已知制剂含有一种与活性化合物物理地或化学地相结合的有机载体材料，以及一种与所述的支载体料相接触的玻璃材料。该玻璃含有可溶性的金属离子。药物的释放受控于离子交换作用引起的玻璃中金属离子的溶解作用。显然玻璃在该制剂中不是一个不溶性的惰性化合物。
包含大量小单位的制剂库的一些好处已在文献中描述。例如当粒子小于1-2毫米时有可能获得从胃进入小肠时可重复出现的单位排空（参看Bogentoft    C.等：食物对于肠衣形式的乙酰水杨酸的吸收的影响，Europ.J.Clin.Pharmacol（1978年），14卷351-355页）。药物在胃肠道中大面积分散能够使总通过时间更具重现性，这对吸收过程是有利的（参看Edgar    B。等：用检测血中和尿中稳定状态的水杨酸及其代谢物的水平比较两种肠衣乙酰水杨酸制剂。Biopharmaceu tics    &    Drug    Disposition。（1984年5卷251-260页）。此外当药物剂量在肠子中发散时，多单位制剂优于单一单位制剂。局部刺激的危险和由于消化道收缩引起的一些药量积聚也认为是较低的（参看McMahan    F.G.等：补充氯化钾后刺激性药物的胃肠道损伤：一个控制的临床试验The    Lancet，11月13日1059-1061页）。
多单位制剂的又一好处是它可以分成具有相同吸收性能的较小部分。这样，在选择剂量大小时，就可能有较大的灵活性。
本发明涉及一种可以控制释放一种或多种药物活性化合物的新型制剂。
该制剂由大量不溶性小粒子，即核心组成，这些核心表面被药物活性化合物复盖。核心的大小是0.1-2毫米，最好0.1-0.5毫米，由不溶性惰性材料组成。不溶性的意义是：该材料不溶于水，生理液体或一般用于静脉输注的液体内。不溶性惰性材料的例子有二氧化硅、玻璃或塑料树脂颗粒。塑料材料的适宜类型是可用于医药的塑料，如聚丙烯或聚乙烯，最好是聚丙烯。核心材料应该具有标准的大小和形状，最好是有平滑表面的球状。最好，核心材料应该具有足够高的密度，这可使它适合于流化床处理。更进一步，该核心材料要有高纯度也很重要，也就是说，不含可溶性的杂质。
药物活性化合物最好先配成溶液，再用喷雾法用于核心材料上。因此该活性化合物在不溶性核心上形成一个致密层。所用的药物活性化合物是具有心血管、胃肠道或化疗效应的药物，特别是肾上腺素β-阻断剂和抗生素。能用于核心材料上的适宜的药物活性化合物的例子有心得舒、美多心安、奎尼丁、镁和氨苄西林的盐。产生的颗粒或 小珠的大小为0.2-3.0毫米，最好0.3-1.0毫米。然而对于大部分需要做成控制释放制剂的药物，只要它们能溶于某一溶剂并且此溶剂又能在干燥过程中除掉，都有可能按照上述方法制成控制释放制剂。
本发明的这些小珠是紧密的，这意味着孔隙度少于15%。
小珠用聚合物的膜包衣以限制和控制药物释放。聚合物的膜能根据不同的释放曲线图，例如PH相关的、肠包衣、PH无关的、要或不要延缓时间来释放药物。最重要的用途是在PH1-8范围内与PH无关的控制释放。适宜的聚合物的材料例子有乙基纤维素，羟丙基甲基纤维素羟丙基纤维素，邻苯二甲酸羟丙基甲基酯（例如HP55），乙酸邻苯二甲酸纤维素，EudragitRRL，EudragitRRS。乙基纤维素能单独使用或与例如水溶性的聚合物如羟丙基甲基纤维素合并使用，以调整包衣层的渗透性。
不同粘度等级的乙基纤维素都可以使用，在下面给出的例子中，使用了粘度为10、50或100厘泊的乙基纤维素，但其它类型的乙基纤维素也是适用的。
EudragitR是一些以丙烯酸树脂为基础的由Roehm Pharma。生产的薄膜包衣物料的商品名称，例如Eudragit RL和RS是由丙烯酸酯和甲基丙烯酸酯合成的含少量季铵基团的共聚物。这些铵基团与其余中性的（甲基）丙烯酸酯的摩尔比，对EudragitRRL为1∶20，对EudragitRRS为1∶40，从而产生不同的渗透特性。其它能够使用的Eudragit变体有Eudragit L、Eudragit S和Eudragit E。
为了改良膜的工艺性质或修改释放特征，在聚合物的溶液中可以加色素和/或增塑剂。可以使用的增塑剂的例子是柠檬酸酯、乙酰化单甘油酯和甘油三乙酸酯。
新制剂有若干优点，例如颗粒含有高百分数的活性成分，且不受可溶性的惰性化合物污染，例如乳糖或糖的核心用治疗用的活性化合物包衣正是这个情况。当制剂用于非肠道给药时这一点特别重要。
用小的致密颗粒例如二氧化硅作为核心材料，有可能获得具有高浓度活性化合物的小珠（粒剂），这对于高剂量制剂是个优点，例如氯化镁。
新制剂的一个优点是：包裹用活性化合物复盖的不溶性核心与包裹具有可溶性核心材料的制剂，二者相比较时，为了延缓药物释放，一般来说，前者需要较少的聚合物材料（参看图1）。按照本发明的制剂能以各种途径给药，例如口服或非肠道给药。一个静脉给药的例子是通过在欧洲专利（EP-B1-59694）中描述的药物给予装置给药的。
当把本发明的活性化合物包衣小珠用于口服时，有可能将制剂加工成颗粒填入硬明胶胶囊、填入小药囊中或加工成片剂而给药后仍然可以得到所希望的血浆浓度曲线和持续有效时间。
当小珠做成片剂时，它们与含有微晶纤维素（如AvicelR）的添加剂混合，这样改进压片的性能，并促进片剂的崩解，释放出单个的小珠。
利用本发明，可能在减少给药次数时，而在下次给药前的整个期间血浆中仍具有几乎恒定的药物浓度。用新制剂常常是一天一个单剂量用药就足够了。
控制释放制剂的制造方法是本发明的另一方面。药物活性化合物溶于合适的溶剂例如二氯甲烷、乙醇、异丙醇或水中，并在包衣盘中喷到不溶性的核心材料上面或最好在流化床中喷施，干燥除去溶剂。然后将得到的小珠用上述聚合物层包衣。聚合物的混合物溶于溶剂如乙醇、异丙醇和/或二氯甲烷中。喷雾可以在包衣盘中进行，但最好在流化床中进行。乙基纤维素也可通过水分散体系（乳液）喷施。
当需要有控制地和恒定地释放治疗用活性化合物时，本发明的制剂是特别有利的。关于治疗用活性化合物的控制释放的方法是本发明的又一方面。
通过下列实施例对本发明进行详细说明：
例1
核心
美多心安反丁烯二酸盐    1440克
二氯甲烷    9618克
乙醇95%    3888克
SiO2（0.15-0.25毫米） 375克
聚合物层
乙基纤维素10厘泊    265.6克
羟丙基甲基纤维素    58.4克
柠檬酸乙酰基三丁基酯    36.0克
二氯甲烷    6141克
异丙醇    1544克
在流化床成粒机中将美多心安反丁烯二酸盐的95%乙醇溶液喷施到二氧化硅核心上。这样形成的小珠400克（0.4-0.63 毫米部分）用含有10厘泊乙基纤维素、羟丙基甲基纤维素和柠檬酸乙酰基三丁基酯的聚合物溶液覆盖，复盖方法是将上述物质的二氯甲烷和异丙醇溶液喷施在上述400克小珠上。然后将包衣的小珠填入硬明胶胶囊中。
例2-3和参考例1
核心
2    3    参考例1
美多心安琥珀酸盐    1440克    1440克    1440克
二氯甲烷    9618克    9618克    9618克
乙醇95%    3888克    3888克    3888克
SiO2（0.15-0.25毫米） 375克
玻璃（0.2毫米）    375克
NaCl（0.15-0.25毫米）    375克
聚合物层
400克上面的颗粒（0.4-0.5毫米部分）用下列物质的组合物包衣
乙基纤维素10厘泊    52.3克
柠檬酸乙酰基三丁基酯    8.6克
二氯甲烷    1111克
异丙醇    218克
美多心安琥珀酸盐的95%乙醇和二氯甲烷溶液，分别喷雾到二氧化硅、玻璃和氯化钠核心上。这样形成的小珠用喷雾法，含有粘度为10厘泊的乙基纤维素和柠檬酸乙酰基三丁基酯的二氯甲烷和异丙醇溶液包衣。图1说明在20小时期间内美多心安琥珀酸盐的累积释 放情况。从图中可以看到，当活性化合物用于二氧化硅或玻璃上时，活性化合物可以控制地和几乎恒定地释放，而可溶性氯化钠的核心，产生相当高的起始释放速率，图2（下面参考例2）也说明了这一点，该例是用可溶性氯化钾作为核心材料。
参考例2
核心
美多心安琥珀酸盐    2000克
KCl（0.1-0.2毫米）    400克
二氯甲烷    13360克
乙醇95%    7900克
参考例2的400克颗粒用包括下列聚合物的组合物包衣：
聚合物层
乙基纤维素10厘泊    135.3克
EudragitRRS 27.4克
柠檬酸乙酰基三丁基酯    27.4克
二氯甲烷    4469克
异丙醇    661克
该颗粒按前面例子中所述方法加工。
例4-6
核心    例
4    5    6
美多心安琥珀酸盐    1440克    1440克    1440克
二氯甲烷    9618克    9618克    9618克
乙醇95%    3888克    3888克    3888克
SiO2（0.15-0.2毫米） 375克
SiO2（0.25-0.3毫米） 375克
SiO2（0.4-0.5毫米） 375克
按照例4-6的400克颗粒以包括下列聚合物的组合物包衣：
聚合物层
按照下面各例制成颗粒
4    5    6
乙基纤维素10厘泊    187.2克    144.0克    92.2克
羟丙基甲基纤维素    46.8克    36.0克    23.0克
柠檬酸乙酰基三丁基酯    26.0克    20.0克    12.8克
二氯甲烷    4428克    3408克    2168克
异丙醇    1114克    858克    546克
该制剂按照上述方法加工。在表Ⅰ中给出美多心安琥珀酸盐在20小时期间内的释放。所有制剂都在长时间内使药物得以控制释放。
例7
核心
氯化镁，六水合物    1100克
乙醇99.5%    6200克
二氧化硅（0.15-0.30毫米）    400克
聚合物层
乙基纤维素50厘泊    533克
二氯甲烷    14107克
异丙醇    5481克
将氯化镁（MgCl2）的99.5%乙醇溶液喷雾到二氧化硅 的核心上。400克这样形成的小珠通过粘度为50厘泊的乙基纤维素的二氯甲烷-异丙醇溶液包衣，得到含有347毫克/克氯化镁（MgCl2）的颗粒。在体外，1小时后药物释放为38%，2小时后为58%和6小时后为82%。
例8
核心
氨苄西林-Na    600克
乙醇95%    894克
纯净水    1020克
玻璃（0.5毫米）    500克
聚合物层
乙基纤维素100厘泊    15克
二氯甲烷    600克
异丙醇    150克
氨苄西林-Na的乙醇/水溶液喷雾到玻璃核心上，然后将500克的氨苄西林-Na小珠用100厘泊乙基纤维素的二氯甲烷/异丙醇的聚合物溶液包衣。在体外溶解40分钟后，药物含量的50%从小珠中释放出来。
例9
核心
美多心安琥珀酸盐    1440克
二氯甲烷    9618克
乙醇95%    3888克
SiO2（0.15-0.25毫米） 375克
聚合物层
乙基纤维素N-10    166.2克
羟丙基甲基纤维素    39.0克
柠檬酸乙酰基三丁基酯    22.8克
二氯甲烷    3889克
异丙醇    978克
片剂添加剂
微晶纤维素    429.3克
玉米淀粉    67.1克
乳糖粉    40.3克
聚乙烯吡咯酮（polyvidone）    55.5克
纯净水    314.7克
硬脂酸镁    1.2克
片剂包衣（12，500片）
羟丙基甲基纤维素6厘泊    159.6克
聚乙二醇6000    39.9克
染料二氧化钛    39.9克
纯净水    1356克
石蜡    1.6克
按照前面例子中描述的过程将美多心安琥珀酸盐喷雾到二氧化硅的核心上。这样得到的400克小珠（0.4-0.63毫米部分）用上述聚合物溶液包衣。美多心安琥珀酸盐的包衣小珠与添加剂等份混合，在加入0.1%硬脂酸镁后，干燥的混合物压制成片，最后该片子在包衣盘中用上述聚合物溶液包衣。
用很小的致密的SiO2颗粒（0.15-0.25毫米）作核心材料，有助于在形成的小珠（0.4-0.63毫米）中有很高的药物含量，因此减小了最后制剂的体积。
表1总结了例1-6和9及参考例1和2的制剂的药物释放数据。
生物药剂学研究
本发明的口服应用（例9）说明于图3。为了寻找每日一次剂量并在24小时内有稳定的血浆浓度，将多单位体系用于美多心安琥珀酸盐。
将含有单剂量的190毫克美多心安琥珀酸盐（相当于200毫克美多心安酒石酸盐）的本发明的控制释放制剂给予10个健康的男性受试者。所述美多心安的血浆浓度与用单剂量的持续释放片剂（Durules
Figure 861066510_IMG1
）之后的血浆浓度比较（该持续释放片剂是根据不溶性基质原理含有200毫克美多心安酒石酸盐制成的）。可以看到，按照本发明的制剂给出几乎不变的美多心安的血浆浓度，而基质片剂在给药后的最初几小时内血浆浓度有一个所不希望有的高峰。
实行本发明的最好模式在目前认为是例9。
表1.在磷酸盐缓冲液PH6.8中美多心安的体外累积释放方法：USP仪器    NOⅡ，旋转桨100转/分
Figure 861066510_IMG2

Claims (9)

1、生产控制释放产品时用的小珠的制备方法，其特征在于将溶于溶剂的药物活性化合物喷雾到大小为0.1-2毫米的不溶性核心材料上，干燥除去溶剂，得到用活性化合物紧密层复盖的，具有0.2-3.0毫米大小的小珠，而后，得到的小珠再用控制释放的聚合物的膜复盖。
2、根据权利要求1的方法，其特征在于核心材料大小为0.1-0.5毫米，而用药物活性化合物复盖了的所述核心材料大小为0.3-1.0毫米。
3、根据权利要求1的方法，其特征在于核心材料是二氧化硅。
4、根据权利要求1的方法，其特征在于核心材料是小颗粒的玻璃。
5、根据权利要求1的方法，其特征在于小珠中含有一种希望不立即释放的药物活性化合物。
6、根据权利要求1的方法，其特征在于药物活性化合物是以口服或非肠道给药。
7、根据权利要求1的方法，其特征在于药物活性化合物是用于心血管、胃肠道或化疗方面。
8、根据权利要求1的方法，其特征在于药物活性化合物是肾上腺素β-阻断剂的盐。
9、根据权利要求1的方法，其特征在于药物活性化合物是抗生素。
CN86106651A 1985-10-11 1986-10-11 生产控制释放产品时用的小珠的制备方法 Expired - Lifetime CN1025283C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE8504720A SE450087B (sv) 1985-10-11 1985-10-11 Korn med kontrollerad frisettning av farmaceutiskt aktiva emnen som anbringats teckande pa ett kompakt olosligt kernmaterial
SE8504720-7 1985-10-11

Publications (2)

Publication Number Publication Date
CN86106651A CN86106651A (zh) 1987-04-15
CN1025283C true CN1025283C (zh) 1994-07-06

Family

ID=20361705

Family Applications (1)

Application Number Title Priority Date Filing Date
CN86106651A Expired - Lifetime CN1025283C (zh) 1985-10-11 1986-10-11 生产控制释放产品时用的小珠的制备方法

Country Status (24)

Country Link
US (1) US4927640A (zh)
EP (1) EP0277127B1 (zh)
JP (1) JP2560019B2 (zh)
KR (1) KR940000098B1 (zh)
CN (1) CN1025283C (zh)
AU (1) AU593038B2 (zh)
CS (1) CS268819B2 (zh)
CY (1) CY1764A (zh)
DD (1) DD266734A5 (zh)
DK (1) DK175592B1 (zh)
ES (1) ES2003139A6 (zh)
FI (1) FI97686C (zh)
GR (1) GR862526B (zh)
HU (1) HU199677B (zh)
IE (1) IE58967B1 (zh)
IS (1) IS1530B (zh)
NZ (1) NZ217697A (zh)
PH (1) PH24739A (zh)
PL (1) PL148624B1 (zh)
PT (1) PT83508B (zh)
SE (1) SE450087B (zh)
SU (1) SU1706373A3 (zh)
WO (1) WO1987002240A1 (zh)
ZA (1) ZA866861B (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100370990C (zh) * 1998-12-24 2008-02-27 詹森药业有限公司 控释加兰他敏组合物

Families Citing this family (150)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5270056A (en) * 1985-10-25 1993-12-14 Aktiebolaget Hassle Particle having a dyed coke indicator and a pharmaceutical coating for parenteral administration of the pharmaceutical
GB8707416D0 (en) * 1987-03-27 1987-04-29 Wellcome Found Pharmaceutical formulations
US5612059A (en) * 1988-08-30 1997-03-18 Pfizer Inc. Use of asymmetric membranes in delivery devices
ATE118345T1 (de) * 1990-08-07 1995-03-15 Pfizer Verwendung von interfacial polymerisierten membranen in abgabevorrichtungen.
US5102668A (en) * 1990-10-05 1992-04-07 Kingaform Technology, Inc. Sustained release pharmaceutical preparation using diffusion barriers whose permeabilities change in response to changing pH
DE4333190C2 (de) * 1993-09-29 1996-05-30 Korsatko Werner Univ Prof Dr E Zerbeißtablette mit verzögerter Wirkstoff-Freisetzung
NZ288185A (en) * 1994-06-15 1998-02-26 Dumex Alpharma As Particulate pharmaceutical formulation containing coated cores comprising at least 80% of an inert carrier having a friability of <20%; the inert carrier can be calcium carbonate
SE9402431D0 (sv) * 1994-07-08 1994-07-08 Astra Ab New tablet formulation
SE9402422D0 (sv) * 1994-07-08 1994-07-08 Astra Ab New beads for controlled release and a pharmaceutical preparation containing the same
RU2160094C2 (ru) * 1994-07-08 2000-12-10 Астра Актиеболаг Таблетированная многоединичная лекарственная форма, способ ее получения, упаковка и способ ингибирования секреции желудочной кислоты и/или лечения желудочно-кишечных воспалительных заболеваний
SE9500422D0 (sv) * 1995-02-06 1995-02-06 Astra Ab New oral pharmaceutical dosage forms
SE9600071D0 (sv) 1996-01-08 1996-01-08 Astra Ab New oral formulation of two active ingredients I
SE9600072D0 (sv) * 1996-01-08 1996-01-08 Astra Ab New oral formulation of two active ingredients II
SE512835C2 (sv) * 1996-01-08 2000-05-22 Astrazeneca Ab Doseringsform innehållande en mångfald enheter alla inneslutande syralabil H+K+ATPas-hämmare
SE9600070D0 (sv) 1996-01-08 1996-01-08 Astra Ab New oral pharmaceutical dosage forms
SE9702338D0 (sv) * 1997-06-18 1997-06-18 Astra Ab An analytical method and industrial process including the same
SE9702533D0 (sv) 1997-07-01 1997-07-01 Astra Ab New oral formulation
DK2263660T3 (en) * 1998-05-18 2018-01-02 Takeda Pharmaceuticals Co Orally disintegrating tablets.
EP1100469B1 (en) 1998-07-28 2005-03-23 Takeda Pharmaceutical Company Limited Rapidly disintegrable solid preparation
US6555139B2 (en) 1999-06-28 2003-04-29 Wockhardt Europe Limited Preparation of micron-size pharmaceutical particles by microfluidization
US6245913B1 (en) 1999-06-30 2001-06-12 Wockhardt Europe Limited Synthetic procedure for 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methylthio]-IH-benzimidazole hydrochloride and its conversion to omeprazole
WO2001037811A1 (en) * 1999-11-22 2001-05-31 Akzo Nobel N.V. Composition allowing predefined and controlled release of active ingredient, preparation thereof and use
SE0100200D0 (sv) * 2001-01-24 2001-01-24 Astrazeneca Ab New film coating
SE0100824D0 (sv) * 2001-03-09 2001-03-09 Astrazeneca Ab Method III to obtain microparticles
JP2005514386A (ja) * 2001-12-19 2005-05-19 アストラゼネカ・アクチエボラーグ 新規フィルム・コーティング
EP1499295A4 (en) * 2002-04-05 2006-04-05 Penwest Pharmaceuticals Co EXTENDED RELEASE METOPROLOL FORMULATIONS
EP1515645B1 (en) 2002-06-17 2006-08-16 Tyco Healthcare Group Lp Annular support structures
US20040208932A1 (en) * 2003-04-17 2004-10-21 Ramachandran Thembalath Stabilized paroxetine hydrochloride formulation
WO2004112756A1 (en) * 2003-06-26 2004-12-29 Isa Odidi Proton pump-inhibitor-containing capsules which comprise subunits differently structured for a delayed release of the active ingredient
US7314640B2 (en) * 2003-07-11 2008-01-01 Mongkol Sriwongjanya Formulation and process for drug loaded cores
US20050032879A1 (en) * 2003-08-07 2005-02-10 Temple Okarter Formulations and use of a beta-blocker and an ACE-inhibitor for the treatment of cardiovascular diseases
AU2005212005A1 (en) * 2004-02-11 2005-08-25 Athpharma Limited Chronotherapeutic compositions and methods of their use
US8394409B2 (en) * 2004-07-01 2013-03-12 Intellipharmaceutics Corp. Controlled extended drug release technology
US10624858B2 (en) 2004-08-23 2020-04-21 Intellipharmaceutics Corp Controlled release composition using transition coating, and method of preparing same
US7938307B2 (en) 2004-10-18 2011-05-10 Tyco Healthcare Group Lp Support structures and methods of using the same
US7845536B2 (en) 2004-10-18 2010-12-07 Tyco Healthcare Group Lp Annular adhesive structure
US9364229B2 (en) 2005-03-15 2016-06-14 Covidien Lp Circular anastomosis structures
US8920837B2 (en) 2005-07-01 2014-12-30 Rubicon Research Private Limited Sustained release dosage form
US20070009589A1 (en) * 2005-07-07 2007-01-11 Kandarapu Raghupathi Extended release compositions
EP1915137B8 (de) 2005-08-10 2013-09-11 ADD Advanced Drug Delivery Technologies, Ltd. Orales präparat mit kontrollierter freisetzung
US20070053983A1 (en) * 2005-09-06 2007-03-08 Girish Jain Extended release compositions of metoprolol succinate
US10064828B1 (en) 2005-12-23 2018-09-04 Intellipharmaceutics Corp. Pulsed extended-pulsed and extended-pulsed pulsed drug delivery systems
US9629626B2 (en) 2006-02-02 2017-04-25 Covidien Lp Mechanically tuned buttress material to assist with proper formation of surgical element in diseased tissue
PL1842534T3 (pl) * 2006-02-24 2012-05-31 Teva Pharma Tabletki bursztynianu metoprololu o przedłużonym uwalnianiu oraz sposoby ich wytwarzania
US20090068260A1 (en) * 2006-02-24 2009-03-12 Tomer Gold Beta-1-selective adrenoceptor blocking agent compositions and methods for their preparation
US7793813B2 (en) * 2006-02-28 2010-09-14 Tyco Healthcare Group Lp Hub for positioning annular structure on a surgical device
CN101453993A (zh) * 2006-04-03 2009-06-10 伊萨·奥迪迪 含有机溶胶涂层的受控释放递送物件
US10960077B2 (en) 2006-05-12 2021-03-30 Intellipharmaceutics Corp. Abuse and alcohol resistant drug composition
US20090324717A1 (en) * 2006-07-28 2009-12-31 Farmaprojects, S. A. Extended release pharmaceutical formulation of metoprolol and process for its preparation
US7845533B2 (en) 2007-06-22 2010-12-07 Tyco Healthcare Group Lp Detachable buttress material retention systems for use with a surgical stapling device
AU2007318091B2 (en) 2006-10-26 2013-06-27 Covidien Lp Methods of using shape memory alloys for buttress attachment
US20080107726A1 (en) * 2006-11-01 2008-05-08 Pramod Kharwade Compositions comprising beta-adrenergic receptor antagonists and diuretics
EP2131749B1 (en) 2007-03-06 2016-11-02 Covidien LP Surgical stapling apparatus
US8038045B2 (en) 2007-05-25 2011-10-18 Tyco Healthcare Group Lp Staple buttress retention system
US7665646B2 (en) 2007-06-18 2010-02-23 Tyco Healthcare Group Lp Interlocking buttress material retention system
US8062330B2 (en) 2007-06-27 2011-11-22 Tyco Healthcare Group Lp Buttress and surgical stapling apparatus
US20090280175A1 (en) * 2008-05-09 2009-11-12 Ishwar Chauhan Multilayer Proton Pump Inhibitor Tablets
US20090280173A1 (en) * 2008-05-09 2009-11-12 Ishwar Chauhan Multilayer Omeprazole Tablets
US20100147921A1 (en) 2008-12-16 2010-06-17 Lee Olson Surgical Apparatus Including Surgical Buttress
US9486215B2 (en) 2009-03-31 2016-11-08 Covidien Lp Surgical stapling apparatus
US7967179B2 (en) 2009-03-31 2011-06-28 Tyco Healthcare Group Lp Center cinch and release of buttress material
US8016178B2 (en) 2009-03-31 2011-09-13 Tyco Healthcare Group Lp Surgical stapling apparatus
WO2011013082A1 (en) 2009-07-31 2011-02-03 Ranbaxy Laboratories Limited Multi-layered, multiple unit pharmaceutical compositions
US20150231409A1 (en) 2009-10-15 2015-08-20 Covidien Lp Buttress brachytherapy and integrated staple line markers for margin identification
US9610080B2 (en) 2009-10-15 2017-04-04 Covidien Lp Staple line reinforcement for anvil and cartridge
US9693772B2 (en) 2009-10-15 2017-07-04 Covidien Lp Staple line reinforcement for anvil and cartridge
US8157151B2 (en) 2009-10-15 2012-04-17 Tyco Healthcare Group Lp Staple line reinforcement for anvil and cartridge
US10842485B2 (en) 2009-10-15 2020-11-24 Covidien Lp Brachytherapy buttress
US10293553B2 (en) 2009-10-15 2019-05-21 Covidien Lp Buttress brachytherapy and integrated staple line markers for margin identification
IL210279A0 (en) 2009-12-25 2011-03-31 Dexcel Pharma Technologies Ltd Extended release compositions for high solubility, high permeability acdtive pharmaceutical ingredients
SG174658A1 (en) 2010-04-01 2011-10-28 Theravida Inc Pharmaceutical formulations for the treatment of overactive bladder
US9084602B2 (en) * 2011-01-26 2015-07-21 Covidien Lp Buttress film with hemostatic action for surgical stapling apparatus
US8479968B2 (en) 2011-03-10 2013-07-09 Covidien Lp Surgical instrument buttress attachment
US8789737B2 (en) 2011-04-27 2014-07-29 Covidien Lp Circular stapler and staple line reinforcement material
WO2012154774A1 (en) 2011-05-10 2012-11-15 Theravida, Inc. Combinations of solifenacin and salivary stimulants for the treatment of overactive bladder
US9675351B2 (en) 2011-10-26 2017-06-13 Covidien Lp Buttress release from surgical stapler by knife pushing
US8584920B2 (en) 2011-11-04 2013-11-19 Covidien Lp Surgical stapling apparatus including releasable buttress
US9351731B2 (en) 2011-12-14 2016-05-31 Covidien Lp Surgical stapling apparatus including releasable surgical buttress
US9351732B2 (en) 2011-12-14 2016-05-31 Covidien Lp Buttress attachment to degradable polymer zones
US9010608B2 (en) 2011-12-14 2015-04-21 Covidien Lp Releasable buttress retention on a surgical stapler
US8967448B2 (en) 2011-12-14 2015-03-03 Covidien Lp Surgical stapling apparatus including buttress attachment via tabs
US9113885B2 (en) 2011-12-14 2015-08-25 Covidien Lp Buttress assembly for use with surgical stapling device
US9237892B2 (en) 2011-12-14 2016-01-19 Covidien Lp Buttress attachment to the cartridge surface
US9010612B2 (en) 2012-01-26 2015-04-21 Covidien Lp Buttress support design for EEA anvil
US9326773B2 (en) 2012-01-26 2016-05-03 Covidien Lp Surgical device including buttress material
US9010609B2 (en) 2012-01-26 2015-04-21 Covidien Lp Circular stapler including buttress
US9931116B2 (en) 2012-02-10 2018-04-03 Covidien Lp Buttress composition
US8820606B2 (en) 2012-02-24 2014-09-02 Covidien Lp Buttress retention system for linear endostaplers
US9572576B2 (en) 2012-07-18 2017-02-21 Covidien Lp Surgical apparatus including surgical buttress
US20140048580A1 (en) 2012-08-20 2014-02-20 Covidien Lp Buttress attachment features for surgical stapling apparatus
US9161753B2 (en) 2012-10-10 2015-10-20 Covidien Lp Buttress fixation for a circular stapler
US20140131418A1 (en) 2012-11-09 2014-05-15 Covidien Lp Surgical Stapling Apparatus Including Buttress Attachment
US9192384B2 (en) 2012-11-09 2015-11-24 Covidien Lp Recessed groove for better suture retention
US9295466B2 (en) 2012-11-30 2016-03-29 Covidien Lp Surgical apparatus including surgical buttress
US9681936B2 (en) 2012-11-30 2017-06-20 Covidien Lp Multi-layer porous film material
US9402627B2 (en) 2012-12-13 2016-08-02 Covidien Lp Folded buttress for use with a surgical apparatus
US9204881B2 (en) 2013-01-11 2015-12-08 Covidien Lp Buttress retainer for EEA anvil
US9433420B2 (en) 2013-01-23 2016-09-06 Covidien Lp Surgical apparatus including surgical buttress
US9414839B2 (en) 2013-02-04 2016-08-16 Covidien Lp Buttress attachment for circular stapling device
US9192383B2 (en) 2013-02-04 2015-11-24 Covidien Lp Circular stapling device including buttress material
EP2956124A1 (en) 2013-02-13 2015-12-23 Evonik Röhm GmbH Multiparticulate pharmaceutical composition comprising a multitude of two kinds of pellets
US9504470B2 (en) 2013-02-25 2016-11-29 Covidien Lp Circular stapling device with buttress
US20140239047A1 (en) 2013-02-28 2014-08-28 Covidien Lp Adherence concepts for non-woven absorbable felt buttresses
US9782173B2 (en) 2013-03-07 2017-10-10 Covidien Lp Circular stapling device including buttress release mechanism
US9655620B2 (en) 2013-10-28 2017-05-23 Covidien Lp Circular surgical stapling device including buttress material
AU2014246617A1 (en) 2013-12-23 2015-07-09 Sun Pharmaceutical Industries Limited Multi-layered, multiple unit pharmaceutical compositions
US9844378B2 (en) 2014-04-29 2017-12-19 Covidien Lp Surgical stapling apparatus and methods of adhering a surgical buttress thereto
RU2585023C1 (ru) * 2014-12-18 2016-05-27 Общество с ограниченной ответственностью "Нанолек" Способ гранулирования
US10835216B2 (en) 2014-12-24 2020-11-17 Covidien Lp Spinneret for manufacture of melt blown nonwoven fabric
US10470767B2 (en) 2015-02-10 2019-11-12 Covidien Lp Surgical stapling instrument having ultrasonic energy delivery
AU2016246716B2 (en) 2015-04-10 2020-11-05 Covidien Lp Surgical stapler with integrated bladder
KR102495757B1 (ko) 2016-01-20 2023-02-06 테라비다, 인코포레이티드 다한증을 치료하기 위한 방법 및 조성물
US10959731B2 (en) 2016-06-14 2021-03-30 Covidien Lp Buttress attachment for surgical stapling instrument
US11026686B2 (en) 2016-11-08 2021-06-08 Covidien Lp Structure for attaching buttress to anvil and/or cartridge of surgical stapling instrument
US10874768B2 (en) 2017-01-20 2020-12-29 Covidien Lp Drug eluting medical device
US10925607B2 (en) 2017-02-28 2021-02-23 Covidien Lp Surgical stapling apparatus with staple sheath
US10368868B2 (en) 2017-03-09 2019-08-06 Covidien Lp Structure for attaching buttress material to anvil and cartridge of surgical stapling instrument
US11096610B2 (en) 2017-03-28 2021-08-24 Covidien Lp Surgical implants including sensing fibers
US10849625B2 (en) 2017-08-07 2020-12-01 Covidien Lp Surgical buttress retention systems for surgical stapling apparatus
US10945733B2 (en) 2017-08-23 2021-03-16 Covidien Lp Surgical buttress reload and tip attachment assemblies for surgical stapling apparatus
US11141151B2 (en) 2017-12-08 2021-10-12 Covidien Lp Surgical buttress for circular stapling
US11065000B2 (en) 2018-02-22 2021-07-20 Covidien Lp Surgical buttresses for surgical stapling apparatus
US10758237B2 (en) 2018-04-30 2020-09-01 Covidien Lp Circular stapling apparatus with pinned buttress
US11432818B2 (en) 2018-05-09 2022-09-06 Covidien Lp Surgical buttress assemblies
US11284896B2 (en) 2018-05-09 2022-03-29 Covidien Lp Surgical buttress loading and attaching/detaching assemblies
US11426163B2 (en) 2018-05-09 2022-08-30 Covidien Lp Universal linear surgical stapling buttress
US11219460B2 (en) 2018-07-02 2022-01-11 Covidien Lp Surgical stapling apparatus with anvil buttress
US10806459B2 (en) 2018-09-14 2020-10-20 Covidien Lp Drug patterned reinforcement material for circular anastomosis
US10952729B2 (en) 2018-10-03 2021-03-23 Covidien Lp Universal linear buttress retention/release assemblies and methods
US11730472B2 (en) 2019-04-25 2023-08-22 Covidien Lp Surgical system and surgical loading units thereof
US11478245B2 (en) 2019-05-08 2022-10-25 Covidien Lp Surgical stapling device
US11596403B2 (en) 2019-05-08 2023-03-07 Covidien Lp Surgical stapling device
US11969169B2 (en) 2019-09-10 2024-04-30 Covidien Lp Anvil buttress loading unit for a surgical stapling apparatus
US11571208B2 (en) 2019-10-11 2023-02-07 Covidien Lp Surgical buttress loading units
US11523824B2 (en) 2019-12-12 2022-12-13 Covidien Lp Anvil buttress loading for a surgical stapling apparatus
US11547407B2 (en) 2020-03-19 2023-01-10 Covidien Lp Staple line reinforcement for surgical stapling apparatus
US11337699B2 (en) 2020-04-28 2022-05-24 Covidien Lp Magnesium infused surgical buttress for surgical stapler
US11707276B2 (en) 2020-09-08 2023-07-25 Covidien Lp Surgical buttress assemblies and techniques for surgical stapling
US11399833B2 (en) 2020-10-19 2022-08-02 Covidien Lp Anvil buttress attachment for surgical stapling apparatus
US11534170B2 (en) 2021-01-04 2022-12-27 Covidien Lp Anvil buttress attachment for surgical stapling apparatus
US11596399B2 (en) 2021-06-23 2023-03-07 Covidien Lp Anvil buttress attachment for surgical stapling apparatus
US11510670B1 (en) 2021-06-23 2022-11-29 Covidien Lp Buttress attachment for surgical stapling apparatus
US11672538B2 (en) 2021-06-24 2023-06-13 Covidien Lp Surgical stapling device including a buttress retention assembly
US11678879B2 (en) 2021-07-01 2023-06-20 Covidien Lp Buttress attachment for surgical stapling apparatus
US11684368B2 (en) 2021-07-14 2023-06-27 Covidien Lp Surgical stapling device including a buttress retention assembly
US12076013B2 (en) 2021-08-03 2024-09-03 Covidien Lp Surgical buttress attachment assemblies for surgical stapling apparatus
US11801052B2 (en) 2021-08-30 2023-10-31 Covidien Lp Assemblies for surgical stapling instruments
US11751875B2 (en) 2021-10-13 2023-09-12 Coviden Lp Surgical buttress attachment assemblies for surgical stapling apparatus
US11806017B2 (en) 2021-11-23 2023-11-07 Covidien Lp Anvil buttress loading system for surgical stapling apparatus
US12070213B2 (en) 2022-02-24 2024-08-27 Covidien Lp Surgical medical devices

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH532038A (de) * 1970-05-25 1972-12-31 Ciba Geigy Ag Verfahren zur Herstellung von neuen Cycloheptenderivaten
US3951821A (en) * 1972-07-14 1976-04-20 The Dow Chemical Company Disintegrating agent for tablets
US4123382A (en) * 1973-05-25 1978-10-31 Merck & Co., Inc. Method of microencapsulation
SE418247B (sv) * 1975-11-17 1981-05-18 Haessle Ab Sett att framstella kroppar med reglerad frigoring av en aktiv komponent
US4291016A (en) * 1976-07-27 1981-09-22 Sandoz Ltd. Enteric coated mixture of 4-(2-hydroxy-3-isopropylamino-propoxy) indole and sodium lauryl sulphate
GB1542414A (en) * 1976-08-19 1979-03-21 Standard Telephones Cables Ltd Arrangements for the controlled release of biologically active materials
DE2642032C2 (de) * 1976-09-18 1987-04-30 Rupprecht, Herbert, Prof. Dr., 8400 Regensburg Verfahren zur Inkorporierung von Wirkstoffen in siliciumdioxidhaltige Trägermaterialien und eine siliciumdioxidhaltige Zubereitung
GB1576376A (en) * 1977-03-30 1980-10-08 Benzon As Alfred Multiple-unit drug dose
US4256108A (en) * 1977-04-07 1981-03-17 Alza Corporation Microporous-semipermeable laminated osmotic system
SE426548B (sv) * 1978-12-05 1983-01-31 Haessle Ab Fast farmaceutisk beredning innehallande en terapeutiskt effektiv hjertglykosid och en polymer
US4309404A (en) * 1979-08-09 1982-01-05 American Home Products Corporation Sustained release pharmaceutical compositions
CH655658B (zh) * 1980-09-18 1986-05-15
US4326525A (en) * 1980-10-14 1982-04-27 Alza Corporation Osmotic device that improves delivery properties of agent in situ
US4439195A (en) * 1980-10-14 1984-03-27 Alza Corporation Theophylline therapy
IT1144911B (it) * 1981-03-19 1986-10-29 Pharmatec Spa Composizione farmaceutica a rilascio controllato contenente ibuprofen
GB2098867B (en) * 1981-05-21 1984-10-24 Wyeth John & Brother Ltd Sustained release pharmaceutical composition
JPS57209223A (en) * 1981-06-19 1982-12-22 Tanabe Seiyaku Co Ltd Microcapsule for intracranial anti hypotension and its production
JPS5826816A (ja) * 1981-08-11 1983-02-17 Teisan Seiyaku Kk 球形顆粒からなる持続性複合顆粒剤
US4484921A (en) * 1982-02-01 1984-11-27 Alza Corporation Theophylline therapy utilizing osmotic delivery
US4434153A (en) * 1982-03-22 1984-02-28 Alza Corporation Drug delivery system comprising a reservoir containing a plurality of tiny pills
US4642233A (en) * 1982-03-22 1987-02-10 Alza Corporation Gastrointestinal drug delivery system comprising a hydrogel reservoir containing a plurality of tiny pills
US4649043A (en) * 1982-03-22 1987-03-10 Alza Corporation Drug delivery system for delivering a plurality of tiny pills in the gastrointestinal tract
US4449983A (en) * 1982-03-22 1984-05-22 Alza Corporation Simultaneous delivery of two drugs from unit delivery device
JPS58170712A (ja) * 1982-03-31 1983-10-07 Chiyoda Yakuhin Kk インドメタシン徐放錠
US4681583A (en) * 1982-12-20 1987-07-21 Alza Corporation System for dispersing drug in biological environment
US4578075A (en) * 1982-12-20 1986-03-25 Alza Corporation Delivery system housing a plurality of delivery devices
PH18946A (en) * 1983-04-21 1985-11-14 Elan Corp Plc Controlled absorption pharmaceutical composition
GB2146531B (en) * 1983-09-15 1987-04-29 Stc Plc Controlled release system
SE457505B (sv) * 1984-01-10 1989-01-09 Lejus Medical Ab Laminatbelagd oral farmaceutisk komposition och foerfarande foer dess framstaellning
IT1206166B (it) * 1984-07-26 1989-04-14 Sigma Tau Ind Farmaceuti Dispositivo per rilasciare una sostanza in un fluido di dissoluzione con cinetica di ordine zero e procedimento per la sua preparazione
GB2159715B (en) * 1984-06-04 1988-05-05 Sterwin Ag Pharmaceutical composition in sustained release unit dose form and process for its preparation

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100370990C (zh) * 1998-12-24 2008-02-27 詹森药业有限公司 控释加兰他敏组合物

Also Published As

Publication number Publication date
GR862526B (en) 1987-02-09
SE8504720D0 (sv) 1985-10-11
CS729486A2 (en) 1989-08-14
CS268819B2 (en) 1990-04-11
DK175592B1 (da) 2004-12-13
KR870700344A (ko) 1987-12-28
JP2560019B2 (ja) 1996-12-04
US4927640A (en) 1990-05-22
IS1530B (is) 1993-02-23
JPS63501080A (ja) 1988-04-21
EP0277127A1 (en) 1988-08-10
KR940000098B1 (ko) 1994-01-05
IE862493L (en) 1987-04-11
SE8504720L (sv) 1987-04-12
PL148624B1 (en) 1989-11-30
IS3152A7 (is) 1987-04-12
ES2003139A6 (es) 1988-10-16
PH24739A (en) 1990-10-01
ZA866861B (en) 1987-05-27
PT83508A (en) 1986-11-01
DK287687D0 (da) 1987-06-04
CY1764A (en) 1994-07-15
DK287687A (da) 1987-06-04
SU1706373A3 (ru) 1992-01-15
FI881657A (fi) 1988-04-08
WO1987002240A1 (en) 1987-04-23
SE450087B (sv) 1987-06-09
FI97686B (fi) 1996-10-31
CN86106651A (zh) 1987-04-15
FI881657A0 (fi) 1988-04-08
PT83508B (pt) 1989-05-31
AU593038B2 (en) 1990-02-01
EP0277127B1 (en) 1991-04-10
DD266734A5 (de) 1989-04-12
FI97686C (fi) 1997-02-10
PL261801A1 (en) 1987-08-10
HU199677B (en) 1990-03-28
NZ217697A (en) 1989-04-26
HUT47843A (en) 1989-04-28
AU6529686A (en) 1987-05-05
IE58967B1 (en) 1993-12-01

Similar Documents

Publication Publication Date Title
CN1025283C (zh) 生产控制释放产品时用的小珠的制备方法
CN1023293C (zh) 一种含有美多心安盐的控制释放制剂的制备方法
CN1204885C (zh) 含有非诺贝特的药物组合物及其制备方法
CN1053339C (zh) 受控释放吗啡制剂
CN1160079C (zh) 发泡性肠溶制剂
CN1247190C (zh) 具有难溶性药物速释片芯的缓释包衣片
CN1104891C (zh) 缓释制剂
CN1303998C (zh) 含有达非那新的药物制剂
CN1151844C (zh) 药学活性颗粒的制备
CN1134108A (zh) 用于控释的新颗粒及含有该颗粒的药物制剂
CN1058533A (zh) 控释药物制剂
CN87107792A (zh) 包衣膜及由它制备的组合物
CN1023191C (zh) 生产持续释放异丁丙苯酸制剂的方法
CN1178659C (zh) 控释活性化合物的药物制剂
CN1744889A (zh) 坦洛新的控释药物组合物
CN1081029C (zh) 丙戊酸金属盐缓释片剂
CN1198599C (zh) 长期释放药物的缓释性制剂
CN85109688A (zh) 持续释放茶碱的配方
CN1267089C (zh) 硫酸吗啡微粒,其制备方法及含有该物质的组合物
CN1791390A (zh) 口服的可持续释放的药用组合物
CN1090477C (zh) 含布洛芬的固体组合物
CN1285738A (zh) 卡维地洛的新的口服剂型
CN1043508C (zh) 控制释放治疗系统的液体药用制剂的制备方法
CN1193754C (zh) 释放控制型口服制剂
CN1883473A (zh) 一种度洛西汀肠溶片

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
C17 Cessation of patent right
CX01 Expiry of patent term