公开(公告)号：US20090142402A1

公开(公告)日：2009-06-04

申请号：US12295666

申请日：2007-03-19

Applicant: Gen Takebe ,  Tomonori Kawakami ,  Tokio Takagi ,  Mitsuo Hiramatsu

Inventor： Gen Takebe ,  Tomonori Kawakami ,  Tokio Takagi ,  Mitsuo Hiramatsu

IPC: A61K9/14 ,  B01J19/08 ,  A61P43/00

CPC classification number: A61K9/5123 ,  A61K9/0019 ,  A61K9/10 ,  A61K9/19 ,  A61K9/5138 ,  A61K9/5146 ,  A61K9/5192 ,  A61K31/19 ,  A61K31/44 ,  A61K31/573 ,  A61K41/0019 ,  A61K47/32

Abstract: A method and an apparatus enabling manufacture of a microparticle dispersion liquid at high efficiency in a short time while suppressing drug degradation, etc., are provided. In a dissolving step, a poorly soluble drug and a dispersion stabilizer are dissolved in a volatile organic solvent in a container 13. In a fixing step following the dissolving step, the organic solvent, contained in a solution, is eliminated by evaporation, a pellet-form residue 1 is obtained by the organic solvent elimination, and the residue 1 is fixed on an inner wall of the container 13. In a water injecting step following the fixing step, water 2 is injected into an interior of the container 13. In an irradiating step following the water injecting step, laser light 1, emitted from a laser light source 11, is irradiated on the residue 1 fixed on the inner wall of the container 13, and the residue 1 is thereby pulverized and made into microparticles and a microparticle dispersion liquid, constituted of the microparticles being dispersed in the water 2, is manufactured. The microparticles contain the poorly soluble drug and the dispersion stabilizer.

Abstract translation: 提供了能够在抑制药物劣化等的同时在短时间内高效率地制造微粒分散液的方法和装置。 在溶解步骤中，将难溶性药物和分散稳定剂溶解在容器13中的挥发性有机溶剂中。在溶解步骤之后的定影步骤中，通过蒸发除去溶液中所含的有机溶剂， 通过有机溶剂消除获得残留物1，残留物1固定在容器13的内壁上。在固定步骤之后的水注入步骤中，将水2注入到容器13的内部。 从激光光源11射出的水喷射工序后的照射工序，照射在固定在容器13的内壁上的残渣1上，将残渣1粉碎成微粒， 制造由分散在水2中的微粒构成的微粒分散液。 微粒含有难溶性药物和分散稳定剂。

公开(公告)号：US07597277B2

公开(公告)日：2009-10-06

申请号：US10582786

申请日：2004-12-14

Applicant: Tomonori Kawakami ,  Mitsuo Hiramatsu ,  Tokio Takagi

Inventor： Tomonori Kawakami ,  Mitsuo Hiramatsu ,  Tokio Takagi

IPC: B02C19/18

CPC classification number: B01J19/10 ,  A61J3/07 ,  A61K9/14 ,  A61K9/145 ,  A61K9/146 ,  A61K9/5089 ,  A61K31/00 ,  B01J19/121 ,  B01J2219/0871 ,  B01J2219/089 ,  B02C19/18

Abstract: A production apparatus which includes: a treatment chamber, containing a to-be-treated liquid, made up of water, which is a solvent, and raw material particles of a substance; a laser light source, illuminating laser light for microparticulation onto the to-be-treated liquid; an ultrasonic transducer, irradiating ultrasonic waves for preventing aggregation of microparticles; and a controlling device, controlling the laser light illumination by the laser light source and the ultrasonic wave irradiation by the ultrasonic transducer. A vibration amplitude of the treatment chamber is monitored by means of a microphone and a vibration amplitude measuring device to set the frequency of the ultrasonic waves to a resonance vibration frequency. A microparticle production method and production apparatus that enable substances to be microparticulated efficiently by photo-pulverization, and microparticles are thus realized.

Abstract translation: 一种制造装置，其特征在于，包括：处理室，含有作为溶剂的水构成的被处理液和物质的原料粒子; 激光光源，照射用于微粒化到被处理液体上的激光; 超声波换能器，照射超声波以防止微粒聚集; 以及控制装置，通过激光源控制激光照射和超声波换能器的超声波照射。 通过麦克风和振动幅度测量装置监测处理室的振动幅度，以将超声波的频率设定为共振振动频率。 通过光粉化使微粒化微粒化的微粒生产方法和制造装置，从而实现微粒。

公开(公告)号：US07938344B2

公开(公告)日：2011-05-10

申请号：US10579755

申请日：2004-11-18

Applicant: Tomonori Kawakami ,  Mitsuo Hiramatsu ,  Tokio Takagi

Inventor： Tomonori Kawakami ,  Mitsuo Hiramatsu ,  Tokio Takagi

IPC: B02C19/18

CPC classification number: B01J19/121 ,  B01J2219/00094 ,  B01J2219/00137 ,  B01J2219/0871 ,  B01J2219/0877 ,  B01J2219/0879

Abstract: A to-be-treated body, which contains raw material particles 5 of a substance and with which a solvent 4 of a to-be-treated liquid 2 is made solid, is used, and a laser light source 10, which supplies a laser light of a predetermined wavelength to a treatment chamber 3 that contains the to-be-treated body, is provided to arrange a production apparatus 1A. The laser light from the laser light source 10 is illuminated onto the to-be-treated body to microparticulate the substance in solvent 4. As the to-be-treated body of solid form, a solidified body 6, with which water 4 is solidified by a cooling device 50 and the solidified state is maintained by a thermally insulating layer 30, may be used. Or, as the to-be-treated body, a gel body, with which the solvent is gelled, may be used. The substance can thereby microparticulated efficiently by photo-pulverization.

Abstract translation: 使用含有物质的原料颗粒5并且待处理液体2的溶剂4与其形成固体的待处理体，以及提供激光的激光源10 提供预定波长的光到包含被处理体的处理室3，以布置生产设备1A。 来自激光光源10的激光被照射到被处理体上以使溶剂4中的物质微粒化。作为待固化体的待处理体，凝固体6与水4固化 通过冷却装置50，并且可以使用由隔热层30保持固化状态。 或者，作为被处理体，可以使用溶胶凝胶化的凝胶体。 因此可以通过光粉化有效地使物质微粒化。

公开(公告)号：US20070114306A1

公开(公告)日：2007-05-24

申请号：US10582786

申请日：2004-12-14

Applicant: Tomonori Kawakami ,  Mitsuo Hiramatsu ,  Tokio Takagi

Inventor： Tomonori Kawakami ,  Mitsuo Hiramatsu ,  Tokio Takagi

IPC: B02C19/18

CPC classification number: B01J19/10 ,  A61J3/07 ,  A61K9/14 ,  A61K9/145 ,  A61K9/146 ,  A61K9/5089 ,  A61K31/00 ,  B01J19/121 ,  B01J2219/0871 ,  B01J2219/089 ,  B02C19/18

Abstract: A production apparatus 1A includes: a treatment chamber 3, containing a to-be-treated liquid 2, made up of water 4, which is a solvent, and raw material particles 5 of a substance; a laser light source 10, illuminating laser light for microparticulation onto the to-be-treated liquid 2; an ultrasonic transducer 20, irradiating ultrasonic waves for preventing aggregation of microparticles; and a controlling device 15, controlling the laser light illumination by the laser light source 10 and the ultrasonic wave irradiation by the ultrasonic transducer 20. A vibration amplitude of the treatment chamber 3 is monitored by means of a microphone 30 and a vibration amplitude measuring device 35 to set the frequency of the ultrasonic waves to a resonance vibration frequency. A microparticle production method and production apparatus that enable substances to be microparticulated efficiently by photo-pulverization, and microparticles are thereby realized.

Abstract translation: 制造装置1A包括：处理室3，其含有作为溶剂的水4和物质的原料颗粒5构成的待处理液体2; 激光光源10，照射用于微粒化到待处理液体2上的激光; 超声波换能器20，照射超声波以防止微粒聚集; 控制装置15，控制激光光源10的激光照射和超声波振子20的超声波照射。 通过麦克风30和振动测量装置35监测处理室3的振动幅度，以将超声波的频率设定为共振振动频率。 能够通过光粉化使微粒化微粒化的微粒生产方法和制造装置，从而实现微粒。

公开(公告)号：US20060257489A1

公开(公告)日：2006-11-16

申请号：US10547549

申请日：2004-03-05

Applicant: Tomonori Kawakami ,  Mitsuo Hiramatsu ,  Hiroshi Satozono ,  Tokio Takagi

Inventor： Tomonori Kawakami ,  Mitsuo Hiramatsu ,  Hiroshi Satozono ,  Tokio Takagi

IPC: A61K9/14 ,  B29B9/00

CPC classification number: A61K9/14 ,  A61K31/573 ,  B01J19/121 ,  B01J2219/089

Abstract: In a method for finely pulverizing an organic compound 5 in treatment target liquid 2 to manufacture fine particles of the organic compound 5, a laser beam having a wavelength which is longer than the light absorption band of the organic compound 5 or corresponds to an absorption wavelength of solvent is irradiated to the treatment target liquid 2 to finely pulverize the organic compound 5, thereby manufacturing fine particles of the organic compound 5. According to this manufacturing method, the fine particles can be manufactured with sufficiently preventing photochemical reactions of the organic compound 5 in the treatment target liquid 2. Accordingly, a fine particle manufacturing method and apparatus that can manufacture fine particles while sufficiently preventing photochemical reactions in the organic compound, fine particles, and injectable agent and a manufacturing method for the injectable agent can be implemented.

Abstract translation: 在用于细粉碎处理目标液体2中的有机化合物5以制造有机化合物5的细颗粒的方法中，具有比有机化合物5的光吸收带长的波长或相当于吸收波长的激光束 的溶剂照射到处理对象液体2上以细粉碎有机化合物5，从而制造有机化合物5的细颗粒。 根据该制造方法，可以充分防止有机化合物5在处理对象液2中的光化学反应而制造微粒。 因此，可以实现能够在充分防止有机化合物，微粒和可注射剂中的光化学反应的同时制造微粒的微粒制造方法和装置以及可注射剂的制造方法。

公开(公告)号：US08663702B2

公开(公告)日：2014-03-04

申请号：US12295666

申请日：2007-03-19

Applicant: Gen Takebe ,  Tomonori Kawakami ,  Tokio Takagi ,  Mitsuo Hiramatsu

Inventor： Gen Takebe ,  Tomonori Kawakami ,  Tokio Takagi ,  Mitsuo Hiramatsu

IPC: A61K9/10 ,  B02C23/36 ,  B29B9/10

CPC classification number: A61K9/5123 ,  A61K9/0019 ,  A61K9/10 ,  A61K9/19 ,  A61K9/5138 ,  A61K9/5146 ,  A61K9/5192 ,  A61K31/19 ,  A61K31/44 ,  A61K31/573 ,  A61K41/0019 ,  A61K47/32

Abstract: A method and an apparatus enabling manufacture of a microparticle dispersion liquid at high efficiency in a short time while suppressing drug degradation, etc., are provided. In a dissolving step, a poorly soluble drug and a dispersion stabilizer are dissolved in a volatile organic solvent in a container 13. In a fixing step following the dissolving step, the organic solvent, contained in a solution, is eliminated by evaporation, a pellet-form residue 1 is obtained by the organic solvent elimination, and the residue 1 is fixed on an inner wall of the container 13. In a water injecting step following the fixing step, water 2 is injected into an interior of the container 13. In an irradiating step following the water injecting step, laser light 1, emitted from a laser light source 11, is irradiated on the residue 1 fixed on the inner wall of the container 13, and the residue 1 is thereby pulverized and made into microparticles and a microparticle dispersion liquid, constituted of the microparticles being dispersed in the water 2, is manufactured. The microparticles contain the poorly soluble drug and the dispersion stabilizer.

Abstract translation: 提供了能够在抑制药物劣化等的同时在短时间内高效率地制造微粒分散液的方法和装置。 在溶解步骤中，将难溶性药物和分散稳定剂溶解在容器13中的挥发性有机溶剂中。在溶解步骤之后的定影步骤中，通过蒸发除去溶液中所含的有机溶剂， 通过有机溶剂消除获得残留物1，残留物1固定在容器13的内壁上。在固定步骤之后的水注入步骤中，将水2注入到容器13的内部。 从激光光源11射出的水喷射工序后的照射工序，照射在固定在容器13的内壁上的残渣1上，将残渣1粉碎成微粒， 制造由分散在水2中的微粒构成的微粒分散液。 微粒含有难溶性药物和分散稳定剂。

公开(公告)号：US20070152360A1

公开(公告)日：2007-07-05

申请号：US10579755

申请日：2004-11-18

Applicant: Tomonori Kawakami ,  Mitsuo Hiramatsu ,  Tokio Takagi

Inventor： Tomonori Kawakami ,  Mitsuo Hiramatsu ,  Tokio Takagi

IPC: A61K9/14 ,  B29B9/00

CPC classification number: B01J19/121 ,  B01J2219/00094 ,  B01J2219/00137 ,  B01J2219/0871 ,  B01J2219/0877 ,  B01J2219/0879

Abstract: A to-be-treated body, which contains raw material particles 5 of a substance and with which a solvent 4 of a to-be-treated liquid 2 is made solid, is used, and a laser light source 10, which supplies a laser light of a predetermined wavelength to a treatment chamber 3 that contains the to-be-treated body, is provided to arrange a production apparatus 1A. The laser light from the laser light source 10 is illuminated onto the to-be-treated body to microparticulate the substance in solvent 4. As the to-be-treated body of solid form, a solidified body 6, with which water 4 is solidified by a cooling device 50 and the solidified state is maintained by a thermally insulating layer 30, may be used. Or, as the to-be-treated body, a gel body, with which the solvent is gelled, may be used. The substance can thereby microparticulated efficiently by photo-pulverization.

Abstract translation: 使用含有物质的原料颗粒5并且待处理液体2的溶剂4与其形成固体的待处理体，以及提供激光的激光源10 设置含有待处理体的处理室3的预定波长的光，以配置制造装置11A。将来自激光光源10的激光照射到被处理体上， 在溶剂中微粒化物质4。 作为固体形式的被处理体，可以使用通过冷却装置50固化水4和固化状态的凝固体6，由绝热层30维持。 或者，作为被处理体，可以使用溶胶凝胶化的凝胶体。 因此可以通过光粉化有效地使物质微粒化。

公开(公告)号：US20090087460A1

公开(公告)日：2009-04-02

申请号：US12235825

申请日：2008-09-23

Applicant: Gen Takebe ,  Mitsuo Hiramatsu ,  Tokio Takagi

Inventor： Gen Takebe ,  Mitsuo Hiramatsu ,  Tokio Takagi

IPC: A61K9/10 ,  A61K47/32 ,  A61K31/337

CPC classification number: A61K31/337 ,  A61K9/0019 ,  A61K9/10 ,  A61K9/1617 ,  A61K9/1635 ,  A61K9/1694 ,  A61K9/5123 ,  A61K9/5138 ,  A61K9/5192

Abstract: In a dissolving step, in a container 13, a poorly soluble drug and a dispersion stabilizer (polyvinylpyrrolidone and sodium lauryl sulfate) are dissolved in a volatile organic solvent. In a solid composition forming step following the dissolving step, the organic solvent contained in the solution is removed by evaporation, and by the organic solvent removal, a solid composition 1 is obtained as a residue, and the solid composition 1 becomes fixed on the inner wall of the container 13. In a water injecting step following the solid composition forming step, water 2 is injected into the interior of the container 13. In a microparticle dispersion liquid preparing step following the water injecting step, laser light L emitted from a laser light source 11 is irradiated on the solid composition 1 fixed on the inner wall of the container 13 and optical energy is thereby applied to the solid composition 1.

Abstract translation: 在溶解步骤中，在容器13中，将难溶性药物和分散稳定剂（聚乙烯吡咯烷酮和十二烷基硫酸钠）溶解在挥发性有机溶剂中。 在溶解步骤之后的固体组合物形成步骤中，通过蒸发除去溶液中所含的有机溶剂，通过除去有机溶剂，得到固体组合物1作为残留物，固体组合物1固定在内部 在固体组合物形成步骤之后的水注入步骤中，将水2注入容器13的内部。在水喷射步骤之后的微粒分散液制备步骤中，从激光发射的激光L 光源11照射在固定在容器13的内壁上的固体组合物1上，由此将光能施加到固体组合物1上。

公开(公告)号：US09168504B2

公开(公告)日：2015-10-27

申请号：US13583361

申请日：2011-03-10

Applicant: Tokio Takagi ,  Mitsuo Hiramatsu ,  Gen Takebe ,  Naota Akikusa ,  Kazuue Fujita ,  Tatsuo Dougakiuchi

Inventor： Tokio Takagi ,  Mitsuo Hiramatsu ,  Gen Takebe ,  Naota Akikusa ,  Kazuue Fujita ,  Tatsuo Dougakiuchi

IPC: B01J13/00 ,  B01J19/12 ,  A61K9/51 ,  B01J19/00 ,  B02C19/18 ,  B02C23/06

CPC classification number: B01J19/121 ,  A61K9/5138 ,  B01J19/008 ,  B01J19/128 ,  B02C19/18 ,  B02C23/06 ,  B02C2019/183

Abstract: A microparticle dispersion liquid manufacturing apparatus 10 includes a controller 11, a light source 12, an irradiation optical system 13, and a container 14. A solid object 1 is contained in and a solvent 2 is injected into an interior of the container 14 to enable attainment of a state where the solid object 1 is in contact with the solvent 2. The light source 12 repeatedly outputs pulsed light. By repeatedly irradiating the solvent 2 with the pulsed light from the light source 12, expansion and contraction of the solvent 2 is made to occur repeatedly at the irradiated portion, thereby generating a pressure wave in the solvent 2, and the pressure wave is made to act on the solid object 1 to finely pulverize the solid object 1 and thereby manufacture a microparticle dispersion liquid in which microparticles are dispersed in the solvent. A microparticle dispersion liquid manufacturing method and manufacturing apparatus are thereby realized by which both suppression of impurity formation and an increase in efficiency of microparticle formation can be achieved readily.

Abstract translation: 微粒分散液制造装置10包括控制器11，光源12，照射光学系统13和容器14.固体物体1被容纳在溶剂2中并注入到容器14的内部，以使得能够 实现固体1与溶剂2接触的状态。光源12重复输出脉冲光。 通过用来自光源12的脉冲光反复照射溶剂2，使溶剂2的膨胀和收缩在照射部分重复出现，从而在溶剂2中产生压力波，并使压力波变为 作用在固体物体1上以细粉碎固体物体1，从而制造其中微粒分散在溶剂中的微粒分散液。 由此，可以容易地实现微粒分散液的制造方法及制造装置，能够容易地实现抑制杂质形成和微粒形成效率的提高。

公开(公告)号：US08445019B2

公开(公告)日：2013-05-21

申请号：US12235811

申请日：2008-09-23

Applicant: Gen Takebe ,  Tokio Takagi ,  Mitsuo Hiramatsu

Inventor： Gen Takebe ,  Tokio Takagi ,  Mitsuo Hiramatsu

IPC: A61K9/10 ,  B02C23/18

CPC classification number: A61K9/5123 ,  A61K9/1617 ,  A61K9/1635 ,  A61K9/1641 ,  A61K9/1694 ,  A61K9/5138 ,  A61K9/5146 ,  A61K9/5192

Abstract: In a dissolving step, a poorly soluble drug and a dispersion stabilizer are dissolved in a volatile organic solvent. In a fixing step, the organic solvent, contained in a solution obtained in the dissolving step, is removed by evaporation, pellet-form residues 1 are obtained by the organic solvent removal, and the residues 1 are fixed on respective bottom surfaces of a plurality of locations of a container 30. In a water injecting step, water 2 is injected into each of a plurality of recesses 31 of the container 30. In an irradiating step, laser light L, emitted from a light irradiating unit 20, is irradiated simultaneously or successively on the residues 1 fixed on the respective bottom surfaces of the recesses 31 of the container 30, and the residues 1 are thereby pulverized and made into microparticles and a microparticle dispersion liquid, constituted of the microparticles being dispersed in the water 2, is manufactured.

Abstract translation: 在溶解步骤中，将难溶性药物和分散稳定剂溶解在挥发性有机溶剂中。 在固定步骤中，通过蒸发除去在溶解步骤中获得的溶液中所含的有机溶剂，通过除去有机溶剂获得颗粒状残留物1，残留物1固定在多个的各个底面上 在水注入步骤中，将水2注入到容器30的多个凹部31的每一个中。在照射步骤中，从光照射单元20发射的激光L同时照射 或连续地固定在容器30的凹部31的各个底面的残留物1上，然后将残渣1粉碎成微粒，并将由微粒分散在水2中的微粒分散液为 制造。