公开(公告)号：US5851451A

公开(公告)日：1998-12-22

申请号：US766611

申请日：1996-12-13

申请人： Nobuyuki Takechi ,  Seiji Ohtani ,  Akihiro Nagai

发明人： Nobuyuki Takechi ,  Seiji Ohtani ,  Akihiro Nagai

IPC分类号： A61K9/16 ,  A61K9/50 ,  A61K9/52

CPC分类号： A61K9/1647 ,  A61K9/1694 ,  Y10S514/937 ,  Y10S514/938

摘要： Disclosed is a method of producing microspheres which comprises subjecting a w/o/w emulsion or o/w emulsion to an in-water drying method under the following conditions: 1) the amount of microspheres per m.sup.3 of an external aqueous phase is about 0.1 to about 500 kg, 2) the square root of the area (unit: m.sup.2) of the liquid surface in contact with the gas phase is about 0.2 to about 4.5 per the cube root of the volume (unit: m.sup.3) of an external aqueous phase, 3) the w/o/w emulsion or o/w emulsion is replaced at the replacement frequency of about 0.01 to about 10 times/minutes, 4) a gas is blown to the w/o/w emulsion or o/w emulsion at the gas transfer rate near the liquid surface of about 0.1 to about 300 m/second, and 5) the gas is replaced at the replacement frequency of not less than about 0.5 times/minutes; and the method of the present invention increases the rate of solvent removal from microspheres in in-water drying, reduces the amount of solvent in microspheres in a short time.

摘要翻译： 公开了一种制备微球体的方法，其包括在以下条件下使w / o / w乳液或o / w乳液进行水中干燥方法：1）每m3外部水相的微球体的量为约0.1至 约500kg，2）与气相接触的液面的面积（单位：m2）的平方根相对于外部水相的体积的立方根（单位：m3）为约0.2〜约4.5 ，3）w / o / w乳液或o / w乳液以约0.01至约10次/分钟的替换频率替换，4）将气体吹入w / o / w乳液或o / w乳液 在液体表面附近的气体传输速率为约0.1至约300m /秒，以及5）以不小于约0.5次/分钟的替换频率更换气体; 并且本发明的方法增加了水中干燥中微球溶剂去除速率，在短时间内减少了微球中的溶剂量。

公开(公告)号：US6036976A

公开(公告)日：2000-03-14

申请号：US154164

申请日：1998-09-16

申请人： Nobuyuki Takechi ,  Seiji Ohtani ,  Akihiro Nagai

发明人： Nobuyuki Takechi ,  Seiji Ohtani ,  Akihiro Nagai

IPC分类号： A61K9/16 ,  A61K9/42

CPC分类号： A61K9/1647 ,  A61K9/1694 ,  Y10S514/937 ,  Y10S514/938

摘要： Disclosed is a method of producing microspheres which comprises subjecting a w/o/w emulsion or o/w emulsion to an in-water drying method under the following conditions:1) the amount of microspheres per m.sup.3 of an external aqueous phase is about 0.1 to about 500 kg,2) the square root of the area (unit: m.sup.2) of the liquid surface in contact with the gas phase is about 0.2 to about 4.5 per the cube root of the volume (unit: m.sup.3) of an external aqueous phase,3) the w/o/w emulsion or o/w emulsion is replaced at the replacement frequency of about 0.01 to about 10 times/minutes,4) a gas is blown to the w/o/w emulsion or o/w emulsion at the gas transfer rate near the liquid surface of about 0.1 to about 300 m/second, and5) the gas is replaced at the replacement frequency of not less than about 0.5 times/minutes;and the method of the present invention increases the rate of solvent removal from microspheres in in-water drying, reduces the amount of solvent in microspheres in a short time.

摘要翻译： 公开了一种制备微球体的方法，其包括在以下条件下使w / o / w乳液或o / w乳液进行水中干燥方法：1）每m3外部水相的微球体的量为约0.1至 约500kg，2）与气相接触的液面的面积（单位：m2）的平方根相对于外部水相的体积的立方根（单位：m3）为约0.2〜约4.5 ，3）w / o / w乳液或o / w乳液以约0.01至约10次/分钟的替换频率替换，4）将气体吹入w / o / w乳液或o / w乳液 在液体表面附近的气体传输速率为约0.1至约300m /秒，以及5）以不小于约0.5次/分钟的替换频率更换气体; 并且本发明的方法增加了水中干燥中微球溶剂去除速率，在短时间内减少了微球中的溶剂量。

公开(公告)号：US5536735A

公开(公告)日：1996-07-16

申请号：US322485

申请日：1994-10-14

申请人： Nobuyuki Takechi ,  Akihiro Nagai ,  Naoru Hamaguchi

发明人： Nobuyuki Takechi ,  Akihiro Nagai ,  Naoru Hamaguchi

IPC分类号： A61K31/44 ,  A61K47/18 ,  A61K47/22

CPC分类号： A61K47/18 ,  A61K31/44 ,  A61K47/22 ,  A61K9/0019

摘要： This invention comprises a pharmaceutical composition comprising a benzimidazole compound having antiulcer activity and a water-soluble carboxylic acid amide. According to this invention, a water-insoluble benzimidazole compound having antiulcer activity can be solubilized and a stable pharmaceutical composition can be provided. The solid pharmaceutical composition of this invention can be extemporaneously dissolved in sterile distilled water or an infusion (e.g. physiological saline, glucose infusion, etc.) and put to use as an injection with great convenience.

摘要翻译： 本发明包括含有具有抗溃疡活性的苯并咪唑化合物和水溶性羧酸酰胺的药物组合物。 根据本发明，可以溶解具有抗溃疡活性的水不溶性苯并咪唑化合物，并且可以提供稳定的药物组合物。 本发明的固体药物组合物可以临时溶解于无菌蒸馏水或输液（例如生理盐水，葡萄糖输注等）中，并极大地方便地用作注射剂。

公开(公告)号：US07396841B2

公开(公告)日：2008-07-08

申请号：US10344805

申请日：2001-08-17

申请人： Takayuki Doen ,  Masao Nagao ,  Naoki Asakawa ,  Nobuyuki Takechi

发明人： Takayuki Doen ,  Masao Nagao ,  Naoki Asakawa ,  Nobuyuki Takechi

IPC分类号： A61K31/4439 ,  C07D401/12

CPC分类号： A61K9/0019 ,  A61K9/19 ,  A61K31/404 ,  A61K31/4184 ,  A61K31/4439 ,  A61K47/02 ,  A61K47/18 ,  A61K47/26

摘要： An injectable composition comprises a benzimidazole compound having an antiulcer action and a strong alkali (e.g., an alkali metal hydroxide such as sodium hydroxide) in a proportion of about 1 equivalent of the latter relative to 1 mol of the former, and is substantially free from a nonaqueous solvent. The injectable composition may comprise N-methylglucamine, and a saccharide (such as mannitol). The injectable composition may be a freeze-dried preparation. The freeze-dried preparation is dissolvable in or dilutive with a distilled water for injection or an infusion solution without a nonaqueous solvent. The injectable composition is useful as an antiulcer agent.

摘要翻译： 可注射组合物包含具有抗溃疡作用的苯并咪唑化合物和强碱（例如，碱金属氢氧化物如氢氧化钠），其比例相对于前者为1摩尔为约1当量，并且基本上不含 非水溶剂。 可注射组合物可以包含N-甲基葡糖胺和糖（如甘露糖醇）。 可注射组合物可以是冷冻干燥制剂。 冷冻干燥制剂可用注射用蒸馏水或不含非水溶剂的输液进行溶解或稀释。 可注射组合物可用作抗溃疡剂。

公开(公告)号：US6022564A

公开(公告)日：2000-02-08

申请号：US260797

申请日：1999-03-01

申请人： Nobuyuki Takechi ,  Muneo Nonomura ,  Shigehiro Higuchi ,  Toshiharu Beppu

发明人： Nobuyuki Takechi ,  Muneo Nonomura ,  Shigehiro Higuchi ,  Toshiharu Beppu

IPC分类号： A61K9/16 ,  A61K31/38 ,  A61K31/382 ,  A61K31/67 ,  B02C23/06

CPC分类号： A61K31/683 ,  A61K31/38 ,  A61K31/382 ,  A61K31/67 ,  A61K9/1647 ,  B02C23/06

摘要： This invention provides a method for producing a microparticle which comprises pulverizing a solid preparation comprising a compound represented by the formula: ##STR1## wherein ring A is an optionally substituted benzene ring; R is a hydrogen atom or an optionally substituted hydrocarbon group; B is an optionally esterified or amidated carboxyl group; X is --CH(OH)-- or --CO--; k is 0 or 1; and n is 0, 1 or 2 or a pharmaceutically acceptable salt thereof and a biodegradable polymer of .alpha.-hydroxycarboxylic acid in the presence of a pulverizing auxiliary, which can provide microparticles which are less adhesive and involve less aggregation and are thus excellent in drug entrapment ratio and control of drug-release in a desired particle size.

摘要翻译： 本发明提供一种微粒的制造方法，其特征在于，粉碎包括由下式表示的化合物的固体制剂：其中环A为任选取代的苯环; R是氢原子或任选取代的烃基; B是任选酯化或酰胺化的羧基; X是-CH（OH） - 或-CO-; k为0或1; 和n为0,1或2或其药学上可接受的盐和α-羟基羧酸的可生物降解的聚合物，其在粉碎助剂的存在下，可提供粘合性较小并且聚集较少并因此优异的药物捕获的微粒 比例和控制药物释放在所需的粒度。

公开(公告)号：US5723269A

公开(公告)日：1998-03-03

申请号：US612071

申请日：1996-03-07

申请人： Yasaburo Akagi ,  Nobuyuki Takechi ,  Muneo Nonomura

发明人： Yasaburo Akagi ,  Nobuyuki Takechi ,  Muneo Nonomura

IPC分类号： A61K9/16 ,  A61K9/50 ,  A61K9/58

CPC分类号： A61K9/1694 ,  A61K9/1647 ,  A61K9/501 ,  A61K9/5015 ,  Y10S514/963 ,  Y10T428/2985

摘要： A novel microparticle preparation comprising microparticles of a polymer which contain a drug and are at least partially or wholly coated with a water-soluble inorganic salt, a water-soluble organic acid or a water-soluble salt of an organic acid, which acts as an agent for preventing aggregation of the microparticle preparation is disclosed. The preparation is produced by spraying a polymer solution containing a drug and a solution or dispersion of a water-soluble inorganic salt, a water-soluble organic acid or a water-soluble salt of an organic acid from different nozzles and contacting them with each other in a spray dryer. In this procedure, if desired, a non-ionic surfactant may be added to the solution of the water-soluble inorganic salt, the water-soluble organic acid or the water-soluble salt of organic acid, or a solution of non-ionic surfactant may be sprayed from the other nozzle simultaneously.

摘要翻译： 一种新颖的微粒制剂，其包含含有药物并且至少部分或全部被水溶性无机盐，水溶性有机酸或有机酸的水溶性盐的聚合物的微粒，其作为 公开了防止微粒制剂聚集的试剂。 该制剂通过从不同喷嘴喷射含有药物的聚合物溶液和水溶性无机盐，水溶性有机酸或有机酸的水溶性盐的溶液或分散体并将它们彼此接触来制备 在喷雾干燥器中。 在该方法中，如果需要，可以将非离子表面活性剂加入到水溶性无机盐，水溶性有机酸或有机酸的水溶性盐溶液或非离子表面活性剂 可以同时从另一个喷嘴喷射。