公开(公告)号：WO2007059507A3

公开(公告)日：2007-05-24

申请号：PCT/US2006/060914

申请日：2006-11-15

Applicant: BAXTER INTERNATIONAL, INC. ,  BAXTER HEALTHCARE S.A. ,  KIPP, James, E. ,  GUPTA, Pramod

Inventor： KIPP, James, E. ,  GUPTA, Pramod

IPC: A61K47/48 ,  A61K31/38 ,  A61P11/06 ,  A61P29/00 ,  A61P37/08

Abstract: The present invention is directed to formulations of inclusion complexes of lipoxygenase inhibitors and cyclodextrins having a therapeutically effective concentration of the lipoxygenase inhibitor, methods of making the same and methods of treating disease states using the same. Forming cyclodextrin complexes permits the enhancement of the aqueous solubility of lipoxygenase inhibitors which allows higher concentrations of the lipoxygenase in solution. Aqueous formulations of lipoxygenase inhibitors-cyclodextrin complexes are suitable for parenteral or oral administration for treating and/or preventing inflammatory disease states. The aqueous formulations can be lyophilized to prolong storage stability, assist in oral administration and/or provide for convenient and economical packaging.

公开(公告)号：WO2006081000A9

公开(公告)日：2006-08-31

申请号：PCT/US2005045321

申请日：2005-12-15

Applicant: BAXTER INT ,  BAXTER HEALTHCARE SA ,  KIPP JAMES E ,  HAI TON THAT ,  MELNICK BENNETT P

Inventor： KIPP JAMES E ,  HAI TON THAT ,  MELNICK BENNETT P

IPC: C08G65/326 ,  C08G65/334 ,  C08L71/02

CPC classification number: C08G65/334 ,  A61K8/90 ,  A61K9/146 ,  A61K47/34 ,  A61Q19/00 ,  C08G65/326 ,  C08L71/02

Abstract: The present invention is directed to novel compounds, methods of manufacture and methods of use. The present invention is also directed to solid drug/active agent particles having one or more of the compounds of the present invention associated with the surface thereof. The compounds of the present invention are comprised of a non-polar polyether covalently linked to an anionic sulfonate group. The compounds have an amphipathic quality and preferably, are surface active. Such compounds are preferably useful as surface-active agents to coat and stabilize dispersions of particles in a continuous liquid medium. These surface-active agents may be applied in the stabilization of suspensions, emulsions, or liposome formulations intended for pharmaceutical, medical, cosmetic, or agricultural use. The particles that can be prepared by a variety of methods and will preferably comprise a pharmaceutical agent. Pharmaceutical compositions of the present invention can be used to treat amyriad of conditions and can be administered by many routes, including intravenous, intramuscular, subcutaneous, intrathecal, subdural, intracameral, intracerebral, intralesional, topical, oral, buccal, rectal, pulmonary, and nasal.

Abstract translation: 本发明涉及新型化合物，制造方法和使用方法。 本发明还涉及具有与其表面结合的一种或多种本发明化合物的固体药物/活性剂颗粒。 本发明的化合物由与阴离子磺酸盐基团共价连接的非极性聚醚组成。 这些化合物具有两亲性，并且优选具有表面活性。 这些化合物优选用作表面活性剂以涂覆和稳定连续液体介质中的颗粒分散体。 这些表面活性剂可以用于稳定用于药物，医学，化妆品或农业用途的悬浮液，乳液或脂质体制剂。 可以通过多种方法制备并且优选包含药剂的颗粒。 本发明的药物组合物可用于治疗多种病症，并可通过多种途径给药，包括静脉内，肌肉内，皮下，鞘内，硬膜下，前房内，脑内，病灶内，局部，口服，口腔，直肠，肺和 鼻。

公开(公告)号：WO2005123907A2

公开(公告)日：2005-12-29

申请号：PCT/US2005/022992

申请日：2005-06-08

Applicant: BAXTER INTERNATIONAL INC. ,  KIPP, James E. ,  RABINOW, Barrett, E.

Inventor： KIPP, James E. ,  RABINOW, Barrett, E.

IPC: C12N5/06

CPC classification number: A61K49/0002 ,  A61K9/14 ,  A61K35/12 ,  A61K47/6901 ,  A61K2035/124

Abstract: The present invention is concerned with a method of preparing and delivering small particles of a pharmaceutically active material to a mammalian subject for treating diseases or disorders. A preferred embodiment entails: (i) the collection of tissue cells from an animal donor, (ii) selective or non-selective growth of these cells in a cell culture medium to which is added solid particles of a therapeutically active compound, mostly free of a drug carrier (about 10% or less, by weight), and having an average particle size of less than about 100 microns, (iii) contacting the cells in the cell culture medium with the solid particles of therapeutically active compound causing the particles to be taken up by the cells into either the intracellular compartment of the cultured cells, attachment of the active compound as particles to the periphery of such cells, or a combination of intracellular uptake and attachment to the cell surface, (iv) optionally, isolation and/or resuspension of the cells prepared in steps i through iii, (v) administering the cells to the mammalian subject. The pharmaceutically active material can be administered intravenously, intramuscularly, subcutaneously, intradermally, intra-articularly, intrathecally, epidurally, intracerebrally, via buccal route, rectally, topically, transdermally, orally, intranasally, via pulmonary route, intraperitoneally, or combinations threof. After administration, the loaded cells transport the pharmaceutical composition as particles.

Abstract translation: 本发明涉及制备和递送药物活性物质的小颗粒到哺乳动物受试者以治疗疾病或病症的方法。 优选的实施方案包括：（i）从动物供体收集组织细胞，（ii）这些细胞在细胞培养基中的选择性或非选择性生长，其中加入主要不含 药物载体（约10重量％或更少，重量百分比），平均粒度小于约100微米，（iii）使细胞培养基中的细胞与治疗活性化合物的固体颗粒接触， 被细胞吸收到培养细胞的细胞内区室中，将活性化合物作为颗粒附着到这种细胞的周边，或细胞内摄取和附着到细胞表面的组合，（iv）任选的分离和 /或在步骤i至iii中制备的细胞的再悬浮，（v）向哺乳动物受试者施用细胞。 药物活性物质可以静脉内，肌肉内，皮下，皮内，关节内，鞘内，硬膜外，脑内，经口腔途径，直肠，局部，经皮，口服，鼻内，经由肺途径，腹膜内或组合Threof施用。 给药后，加载的细胞将药物组合物作为颗粒转运。

公开(公告)号：WO2004112747A3

公开(公告)日：2004-12-29

申请号：PCT/US2004/018850

申请日：2004-06-15

Applicant: BAXTER INTERNATIONAL INC. ,  RABINOW, Barrett, E. ,  GENDELMAN, Howard, E. ,  KIPP, James, E.

Inventor： RABINOW, Barrett, E. ,  GENDELMAN, Howard, E. ,  KIPP, James, E.

IPC: A61K9/14

Abstract: The present invention is concerned with delivering a pharmaceutical composition to the brain of a mammalian subject for treating brain diseases or disorders. The process includes the steps of: (i) providing a dispersion of the pharmaceutical composition as particles having an average particle size of from about 150 nm to about 100 microns, and (ii) administering the dispersion to the mammalian subject for delivery to the brain of a portion of the pharmaceutical composition by cells capable of reaching the brain. The dispersion of the pharmaceutical composition as particles, for example, can be phagocytised or adsorbed by the cells prior or subsequent to administration into the mammalian subject. The dispersion of the pharmaceutical composition can be administered to the central nervous system or the vascular system. After administration, the loaded cells transport the pharmaceutical composition as particles into the brain.

公开(公告)号：WO2005123907A3

公开(公告)日：2007-08-23

申请号：PCT/US2005022992

申请日：2005-06-08

Applicant: BAXTER INT ,  BAXTER HEALTHCARE SA ,  KIPP JAMES E ,  RABINOW BARRETT E

Inventor： KIPP JAMES E ,  RABINOW BARRETT E

IPC: C12N5/06 ,  A61K9/14 ,  A61K35/12 ,  A61K45/00 ,  A61K47/48 ,  A61K49/00

CPC classification number: A61K49/0002 ,  A61K9/14 ,  A61K35/12 ,  A61K47/6901 ,  A61K2035/124

Abstract: The present invention is concerned with a method of preparing and delivering small particles of a pharmaceutically active material to a mammalian subject for treating diseases or disorders. A preferred embodiment entails: (i) the collection of tissue cells from an animal donor, (ii) selective or non-selective growth of these cells in a cell culture medium to which is added solid particles of a therapeutically active compound, mostly free of a drug carrier (about 10% or less, by weight), and having an average particle size of less than about 100 microns, (iii) contacting the cells in the cell culture medium with the solid particles of therapeutically active compound causing the particles to be taken up by the cells into either the intracellular compartment of the cultured cells, attachment of the active compound as particles to the periphery of such cells, or a combination of intracellular uptake and attachment to the cell surface, (iv) optionally, isolation and/or resuspension of the cells prepared in steps i through iii, (v) administering the cells to the mammalian subject. The pharmaceutically active material can be administered intravenously, intramuscularly, subcutaneously, intradermally, intra-articularly, intrathecally, epidurally, intracerebrally, via buccal route, rectally, topically, transdermally, orally, intranasally, via pulmonary route, intraperitoneally, or combinations threof. After administration, the loaded cells transport the pharmaceutical composition as particles.

Abstract translation: 本发明涉及制备和递送药物活性物质的小颗粒到哺乳动物受试者中用于治疗疾病或病症的方法。 优选的实施方案包括：（i）从动物供体收集组织细胞，（ii）这些细胞在细胞培养基中的选择性或非选择性生长，其中加入主要不含 药物载体（约10重量％或更少，重量百分比），平均粒径小于约100微米，（iii）使细胞培养基中的细胞与治疗活性化合物的固体颗粒接触， 被细胞吸收到培养细胞的细胞内隔室中，将活性化合物作为颗粒附着到这种细胞的周边，或细胞内摄取和附着到细胞表面的组合，（iv）任选的分离和 /或在步骤i至iii中制备的细胞的再悬浮，（v）向哺乳动物受试者施用细胞。 药物活性物质可以通过静脉内，肌肉内，皮下，皮内，关节内，鞘内，硬膜外，脑内，经口颊途径，直肠，局部，经皮，口服，鼻内，经由肺途径，腹膜内或组合Threof施用。 给药后，加载的细胞将药物组合物作为颗粒运输。

公开(公告)号：WO2004112747A2

公开(公告)日：2004-12-29

申请号：PCT/US2004/018850

申请日：2004-06-15

Applicant: BAXTER INTERNATIONAL INC. ,  RABINOW, Barrett, E. ,  GENDELMAN, Howard, E. ,  KIPP, James, E.

Inventor： RABINOW, Barrett, E. ,  GENDELMAN, Howard, E. ,  KIPP, James, E.

IPC: A61K9/00

CPC classification number: A61K9/00 ,  A61K9/0085 ,  A61K9/5123 ,  A61K9/5146 ,  A61K47/6901

Abstract: The present invention is concerned with delivering a pharmaceutical composition to the brain of a mammalian subject for treating brain diseases or disorders. The process includes the steps of: (i) providing a dispersion of the pharmaceutical composition as particles having an average particle size of from about 150 nm to about 100 microns, and (ii) administering the dispersion to the mammalian subject for delivery to the brain of a portion of the pharmaceutical composition by cells capable of reaching the brain. The dispersion of the pharmaceutical composition as particles, for example, can be phagocytised or adsorbed by the cells prior or subsequent to administration into the mammalian subject. The dispersion of the pharmaceutical composition can be administered to the central nervous system or the vascular system. After administration, the loaded cells transport the pharmaceutical composition as particles into the brain.

Abstract translation: 本发明涉及向哺乳动物受试者的脑中递送药物组合物以治疗脑部疾病或病症。 该方法包括以下步骤：（i）提供药物组合物的分散体作为平均粒度为约150nm至约100微米的颗粒，和（ii）向哺乳动物受试者施用分散体以递送至脑 的药物组合物的一部分能够到达脑的细胞。 例如，作为颗粒的药物组合物的分散体可以在给予哺乳动物受试者之前或之后被细胞吞噬或吸附。 药物组合物的分散体可以施用于中枢神经系统或血管系统。 给药后，负载的细胞将药物组合物作为颗粒输送到脑中。

公开(公告)号：WO2009140162A1

公开(公告)日：2009-11-19

申请号：PCT/US2009/043295

申请日：2009-05-08

Applicant: BAXTER INTERNATIONAL INC. ,  BAXTER HEALTHCARE S.A. ,  KIPP, James, E. ,  WONG, Joseph, C., T. ,  NAIR, Lakshmy ,  MILLER, Reagan ,  RABINOW, Barrett, E.

Inventor： KIPP, James, E. ,  WONG, Joseph, C., T. ,  NAIR, Lakshmy ,  MILLER, Reagan ,  RABINOW, Barrett, E.

IPC: A61K9/00 ,  A61K47/10 ,  A61K47/40

CPC classification number: A61K9/0019 ,  A61K47/36 ,  A61K47/40

Abstract: Stable pharmaceutical formulations and methods of making same are provided. In a general embodiment, the present disclosure provides a method of making a stable pharmaceutical formulation comprising adding one or more vitrifying additives to an aqueous pharmaceutical solution to raise the glass transition temperature of the aqueous pharmaceutical solution. The aqueous pharmaceutical solution can be cooled to a temperature of about -50 C to about -10 C. The vitrifying additive enhances the formation of a glass or amorphous solid of the aqueous pharmaceutical solution at cryogenic temperatures (-50 to -10C), and the pharmaceutical formulation can be thawed to liquid form and administered to a mammalian subject.

Abstract translation: 提供稳定的药物制剂及其制备方法。 在一般实施方案中，本公开提供了制备稳定药物制剂的方法，其包括向药物水溶液中加入一种或多种玻璃化添加剂以提高药物水溶液的玻璃化转变温度。 水性药物溶液可以冷却至约-50℃至约-10℃的温度。玻璃化添加剂在低温（-50至-10℃）下增强了药物水溶液的玻璃或无定形固体的形成， 药物制剂可以解冻为液体形式并给予哺乳动物受试者。

公开(公告)号：WO2007124224A3

公开(公告)日：2008-04-17

申请号：PCT/US2007064679

申请日：2007-03-22

Applicant: BAXTER INT ,  BAXTER HEALTHCARE SA ,  RABINOW BARRETT E ,  GENDELMAN HOWARD E ,  KIPP JAMES E

Inventor： RABINOW BARRETT E ,  GENDELMAN HOWARD E ,  KIPP JAMES E

IPC: A61K9/10 ,  A61K9/00 ,  A61K9/51 ,  A61K47/48 ,  A61P31/18

CPC classification number: A61K9/0085 ,  A61K9/10 ,  A61K9/5123 ,  A61K9/5146 ,  A61K47/6901

Abstract: The present invention is concerned with delivering a pharmaceutical composition to a tissue target of a mammalian subject for treating brain diseases or disorders. The process includes the steps of: (i) providing a dispersion of the pharmaceutical composition as particles having an average particle size of from about 150 nm to about 100 microns, and (ii) administering the dispersion to the mammalian subject for delivery to the tissue target of a portion of the pharmaceutical composition by cells capable of reaching the tissue target. The dispersion of the pharmaceutical composition as particles, for example, can be phagocytised or adsorbed by the cells prior or subsequent to administration into the mammalian subject. The dispersion of the pharmaceutical composition can be administered to the central nervous system or the vascular system. After administration, the loaded cells transport the pharmaceutical composition as particles into the tissue target.

Abstract translation: 本发明涉及将药物组合物递送至哺乳动物受试者的组织靶以治疗脑部疾病或病症。 该方法包括以下步骤：（i）提供药物组合物的分散体作为平均粒度为约150nm至约100微米的颗粒，和（ii）向哺乳动物受试者施用分散体以递送至组织 通过能够到达组织靶的细胞的一部分药物组合物的靶标。 例如，作为颗粒的药物组合物的分散体可以在给予哺乳动物受试者之前或之后被细胞吞噬或吸附。 药物组合物的分散体可以施用于中枢神经系统或血管系统。 给药后，负载的细胞将药物组合物作为颗粒输送到组织靶中。

公开(公告)号：WO2007059515A3

公开(公告)日：2007-11-01

申请号：PCT/US2006060939

申请日：2006-11-15

Applicant: BAXTER INT ,  BAXTER HEALTHCARE SA ,  KIPP JAMES E ,  WERLING JANE ,  GUPTA PRAMOD ,  BURESH RITA

Inventor： KIPP JAMES E ,  WERLING JANE ,  GUPTA PRAMOD ,  BURESH RITA

IPC: A61K9/14 ,  A61K9/10 ,  A61K9/19 ,  A61K31/38 ,  A61P1/00 ,  A61P9/10 ,  A61P11/06 ,  A61P17/06 ,  A61P17/10 ,  A61P29/00 ,  A61P35/00 ,  A61P37/08

CPC classification number: A61K9/10 ,  A61K9/0043 ,  A61K9/0048 ,  A61K9/19 ,  A61K9/5146 ,  A61K31/38 ,  A61K31/381

Abstract: Pharmaceutical compositions comprising particles of lipoxygenase inhibitor compounds having an effective average size of from about 10 nm to about 50 microns are provided. More particularly, pharmaceutical compositions of particle of a 5 -lipoxygenase inhibitor compound having an effective average size of from about 50 nm to about 5 microns are provided. The pharmaceutical compositions are in the form of aqueous suspensions with the particle of the 5-lipoxygenase-inhibitor compound present in concentrations of from about 5 to about 200 mg/ml. In addition, methods for making such pharmaceutical compositions are provided. In particular, microprecipitation and direct homogenization in the presence of at least one surfactant are disclosed for making the pharmaceutical compositions.

Abstract translation: 提供了包含有效平均尺寸为约10nm至约50微米的脂氧合酶抑制剂化合物颗粒的药物组合物。 更特别地，提供了具有约50nm至约5微米的有效平均尺寸的5-脂氧合酶抑制剂化合物颗粒的药物组合物。 药物组合物呈含水悬浮液的形式，其中5-脂氧合酶抑制剂化合物颗粒以约5至约200mg / ml的浓度存在。 另外，提供了制备这种药物组合物的方法。 具体而言，公开了用于制备药物组合物的微量沉淀和在至少一种表面活性剂存在下的直接均质化。

公开(公告)号：WO2007059507A2

公开(公告)日：2007-05-24

申请号：PCT/US2006060914

申请日：2006-11-15

Applicant: BAXTER INT ,  BAXTER HEALTHCARE SA ,  KIPP JAMES E ,  GUPTA PRAMOD

Inventor： KIPP JAMES E ,  GUPTA PRAMOD

IPC: A61K47/48

CPC classification number: B82Y5/00 ,  A61K9/0014 ,  A61K9/0019 ,  A61K9/0031 ,  A61K9/0034 ,  A61K9/0043 ,  A61K9/0073 ,  A61K9/19 ,  A61K31/343 ,  A61K31/38 ,  A61K31/381 ,  A61K31/724 ,  A61K47/40 ,  A61K47/6951 ,  A61K2300/00

Abstract: The present invention is directed to formulations of inclusion complexes of lipoxygenase inhibitors and cyclodextrins having a therapeutically effective concentration of the lipoxygenase inhibitor, methods of making the same and methods of treating disease states using the same. Forming cyclodextrin complexes permits the enhancement of the aqueous solubility of lipoxygenase inhibitors which allows higher concentrations of the lipoxygenase in solution. Aqueous formulations of lipoxygenase inhibitors-cyclodextrin complexes are suitable for parenteral or oral administration for treating and/or preventing inflammatory disease states. The aqueous formulations can be lyophilized to prolong storage stability, assist in oral administration and/or provide for convenient and economical packaging.

Abstract translation: 本发明涉及脂氧合酶抑制剂和具有治疗有效浓度的脂氧合酶抑制剂的环糊精的包合物的制剂，其制备方法以及使用其的治疗疾病状态的方法。 形成环糊精复合物允许提高脂氧合酶抑制剂的水溶性，其允许溶液中更高浓度的脂氧合酶。 脂氧合酶抑制剂 - 环糊精复合物的水性制剂适用于肠胃外或口服给药以治疗和/或预防炎性疾病状态。 水性制剂可以冻干以延长储存稳定性，有助于口服给药和/或提供方便和经济的包装。