公开(公告)号：US07090869B2

公开(公告)日：2006-08-15

申请号：US10433156

申请日：2001-11-29

申请人： Yoshihiro Ohmachi ,  Masafumi Misaki ,  Shigeyuki Takada

发明人： Yoshihiro Ohmachi ,  Masafumi Misaki ,  Shigeyuki Takada

IPC分类号： A61K9/14

CPC分类号： A61K9/5031 ,  A61K9/1647 ,  A61K9/1694 ,  A61K9/19 ,  A61K9/5089

摘要： A method for producing a preparation containing a bioactive substance, characterized in that it comprises forming a solid material containing the bioactive substance and a polymer, and contacting the solid material with a high pressure gas. The method allows the production of a preparation which is suppressed in excessive initial release of the bioactive substance immediately after the administration thereof, is capable of releasing a predetermined amount of the bioactive substance over a long period of time, and is extremely reduced in the deterioration of the bioactive substance and in the amount of a residual organic solvent.

摘要翻译： 一种制备含有生物活性物质的制剂的方法，其特征在于，其包括形成含有生物活性物质和聚合物的固体材料，并使固体材料与高压气体接触。 该方法允许在施用之后立即抑制生物活性物质的过度初始释放抑制的制剂能够长时间释放预定量的生物活性物质，并且极度降低劣化 的生物活性物质和残留的有机溶剂的量。

公开(公告)号：US20060241045A1

公开(公告)日：2006-10-26

申请号：US11473034

申请日：2006-06-23

申请人： Yoshihiro Ohmachi ,  Masafumi Misaki ,  Shigeyuki Takada

发明人： Yoshihiro Ohmachi ,  Masafumi Misaki ,  Shigeyuki Takada

IPC分类号： A61K38/16 ,  C07K14/47

CPC分类号： A61K9/5031 ,  A61K9/1647 ,  A61K9/1694 ,  A61K9/19 ,  A61K9/5089

摘要： A method for producing a preparation containing a bioactive substance, characterized in that it comprises forming a solid material containing the bioactive substance and a polymer, and contacting the solid material with a high pressure gas. The method allows the production of a preparation which is suppressed in excessive initial release of the bioactive substance immediately after the administration thereof, is capable of releasing a predetermined amount of the bioactive substance over a long period of time, and is extremely reduced in the deterioration of the bioactive substance and in the amount of a residual organic solvent.

公开(公告)号：US5536623A

公开(公告)日：1996-07-16

申请号：US011457

申请日：1993-01-29

申请人： Yoshihiro Ohmachi ,  Yoshihiko Tsugawa ,  Akihiro Nagai

发明人： Yoshihiro Ohmachi ,  Yoshihiko Tsugawa ,  Akihiro Nagai

IPC分类号： A61K47/48 ,  C08B37/16

CPC分类号： B82Y5/00 ,  A61K47/48969

摘要： The present invention provides 1) a method of producing a complex of a fumagillol derivative of the formula: ##STR1## wherein R.sup.1 is hydrogen; R.sup.2 is halogen, N(O)mR.sup.5 R.sup.6, N+R.sup.5 R.sup.6 R.sup.7.X-- or S(O)nR.sup.5, wherein R.sup.5, R.sup.6 and R.sup.7 are independently an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; X-- is a counter anion; m is 0 or 1; n is an integer of 0 to 2; and R.sup.5 and R.sup.6 together with the adjacent nitrogen or sulfur atom may form an optionally substituted nitrogen- or sulfur-containing heterocyclic group which may form a condensed ring; or R.sup.1 and R.sup.2 are combined to represent a chemical bond; R.sup.3 is 2-methyl-1-propenyl group or isobutyl group; A is oxygen or NR.sup.8, wherein R.sup.8 is hydrogen or an optionally substituted lower alkyl or aryl group; and R.sup.4 is hydrogen, an optionally substituted hydrocarbon group or an optionally substituted acyl group; or a physiologically acceptable salt thereof, with a highly water-soluble cyclodextrin derivative, which comprises mixing the fumagillol derivative or a physiologically acceptable salt thereof with the highly water-soluble cyclodextrin derivative into an aqueous solution, the concentration of the highly water-soluble cyclodextrin derivative being at about 100 mg/ml or more, and 2) the complex of the fumaggillol derivative (I) or physiologically acceptable salt thereof with the highly water-soluble cyclodextrin derivative obtained by the production method 1).The complex of the fumagillol derivative (I) or physiologically acceptable salt thereof with the highly water-soluble cyclodextrin derivative is highly soluble in water, highly stable in storage and can be used as a preparation for injection.

摘要翻译： 本发明提供1）制备下式的烟曲霉醇衍生物的复合物的方法：其中R 1是氢; R2是卤素，N（O）mR5R6，N + R5R6R7.X-或S（O）nR5，其中R5，R6和R7独立地是任选取代的烃基或任选取代的杂环基; X-是抗衡阴离子; m为0或1; n为0〜2的整数， 并且R 5和R 6与相邻的氮或硫原子一起可以形成可以形成稠环的任选取代的含氮或含硫杂环基; 或R1和R2组合以表示化学键; R3是2-甲基-1-丙烯基或异丁基; A是氧或NR8，其中R8是氢或任选取代的低级烷基或芳基; 且R 4为氢，任选取代的烃基或任选取代的酰基; 或其生理上可接受的盐与高度水溶性的环糊精衍生物组合，其包括将烟曲霉醇衍生物或其生理学上可接受的盐与高度水溶性环糊精衍生物混合到水溶液中，高度水溶性环糊精的浓度 衍生物为约100mg / ml以上，以及2）烟曲霉衍生物（I）或其生理学上可接受的盐与通过制备方法1）获得的高度水溶性环糊精衍生物的络合物。 烟曲霉醇衍生物（I）或其生理学上可接受的盐与高度水溶性环糊精衍生物的络合物高度可溶于水，储存高度稳定，可用作注射剂。