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    Method of increasing oral absorption of .beta.-lactam antibiotics
    45.
    发明授权
    Method of increasing oral absorption of .beta.-lactam antibiotics 失效
    增加β-内酰胺抗生素口服吸收的方法

    公开(公告)号：US4470980A

    公开(公告)日：1984-09-11

    申请号：US277445

    申请日：1981-06-25

    Applicant: Takeru Higuchi ,  Toshiaki Nishihata

    Inventor： Takeru Higuchi ,  Toshiaki Nishihata

    IPC: A61K9/20 ,  A61K31/43 ,  A61K31/545 ,  A61K31/60 ,  A61K31/66 ,  A61K45/06 ,  A61K47/12 ,  A61K47/20 ,  A61K31/62

    CPC classification number: A61K47/20 ,  A61K31/43 ,  A61K31/545 ,  A61K31/60 ,  A61K31/66 ,  A61K45/06 ,  A61K47/12 ,  A61K9/2013

    Abstract: A method and drug form are provided for increasing the oral absorption of .beta.-lactam antibiotics such as the penicillins, cephalosporins and related chemical species by the oral administration of said .beta.-lactam antibiotics in a suitable pharmaceutically accepted excipient to which has been added a hydroxy aryl or hydroxy aralkyl acid or salt, amide or ester thereof. The hydroxyaryl or hydroxyaralkyl acid or salt, amide or ester thereof is present in the drug form in quantities sufficient to be effective in enhancing the rate of oral absorption of the .beta.-lactam antibiotic.

    Abstract translation: 提供了一种方法和药物形式，用于通过在合适的药学上可接受的赋形剂中口服施用所述β-内酰胺抗生素来增加β-内酰胺抗生素如青霉素，头孢菌素和相关化学物质的口服吸收，向其中加入羟基 芳基或羟基芳烷基酸或其盐，酰胺或酯。 羟基芳基或羟基烷基酸或其盐，酰胺或其酯以足以有效提高β-内酰胺抗生素口服吸收速率的药物形式存在。

    Complexes of doxorubicin exhibiting enhanced stability
    47.
    发明授权
    Complexes of doxorubicin exhibiting enhanced stability 失效
    多柔比星复合物表现出增强的稳定性

    公开(公告)号：US4246399A

    公开(公告)日：1981-01-20

    申请号：US779847

    申请日：1977-03-21

    Applicant: Takeru Higuchi ,  Pramod M. Kotwal

    Inventor： Takeru Higuchi ,  Pramod M. Kotwal

    IPC: C07H15/252 ,  C07H15/24 ,  A61K31/71

    CPC classification number: C07H15/252 ,  Y10S514/883 ,  Y10S514/908

    Abstract: Complexes of the formula:A.X.sub.nwherein A represents doxorubicin; wherein X represents Ca.sup.++, Mg.sup.++, Zn.sup.++, or Ni.sup.++ ; and wherein n represents one or two having enhanced stability are disclosed.The above-described compounds are inorganic complexes of a well-known and regulatory approved compound, doxorubicin, useful in the treatment of a variety of carcinomas. These complexes offer enhanced stability over doxorubicin per se.

    Abstract translation: 式的络合物：A.Xn其中A表示多柔比星; 其中X表示Ca ++，Mg ++，Zn ++或Ni ++; 并且其中n表示具有增强的稳定性的一种或两种。 上述化合物是可用于治疗各种癌症的公知和调节批准的化合物多柔比星的无机复合物。 这些复合物比多柔比星本身提供了更强的稳定性。

    Osmotic device with compartment for governing concentration of agent dispensed from device
    48.
    发明授权
    Osmotic device with compartment for governing concentration of agent dispensed from device 失效
    渗透装置具有用于从装置分配的药剂浓度的隔室

    公开(公告)号：US4210139A

    公开(公告)日：1980-07-01

    申请号：US4180

    申请日：1979-01-17

    Applicant: Takeru Higuchi

    Inventor： Takeru Higuchi

    IPC: A61K9/00 ,  A61M7/00

    CPC classification number: A61K9/0004

    Abstract: An osmotic device is disclosed for dispensing a drug. The device comprises an exterior wall surrounding a first and second compartment. The first compartment is in contact with the exterior wall and the second compartment is surrounded by an interior wall that is in contact with the exterior wall. A passageway exists through the exterior wall connecting the first compartment with the exterior of the device, and a passageway exists through the interior wall connecting the second with the first compartment. The first compartment contains an osmotic solute that exhibits an osmotic pressure gradient across the wall against an external fluid, and the second compartment contains a drug that exhibits an osmotic pressure gradient across the wall against the fluid. The exterior and the interior walls are permeable to the passage of the fluid, and they are impermeable to the passage of solute and drug, but the rate of fluid, permeability is greater through the exterior than through the interior wall. In operation, fluid in imbibed through the walls into the compartments and at a greater rate into the first compartment forming a more dilute solution therein than the drug solution formed in the second compartment, said drug solution passing from the second compartment through the passageway into the compartment and being diluted in the first compartment, with the diluted drug solution passing from the first compartment through the passageway to the exterior of the device.

    Abstract translation: 公开了用于分配药物的渗透装置。 该装置包括围绕第一和第二隔室的外壁。 第一隔室与外壁接触，第二隔室由与外壁接触的内壁包围。 通过连接第一隔室与装置的外部的外壁存在通道，并且通过将第二隔室与第一隔室连接的内壁存在通道。 第一隔室包含渗透性溶质，其表现出跨过壁抵抗外部流体的渗透压梯度，并且第二隔室含有一种药物，其表现出跨过该壁抵抗流体的渗透压梯度。 外壁和内壁对于流体的通道是可渗透的，并且它们对于溶质和药物的通过是不可渗透的，但是流体的渗透率通过外部比通过内壁更大。 在操作中，流体通过壁吸入隔间，并以更大的速率吸入第一隔室，形成比第二隔室中形成的药物溶液更稀的溶液，所述药物溶液从第二隔室通过通道进入 并且在第一隔室中稀释，稀释的药物溶液从第一隔间通过通道到达设备的外部。

    Method for inducing rapid therapeutically effective antimalarial levels of certain selected conventional antimalarials
    49.
    发明授权
    Method for inducing rapid therapeutically effective antimalarial levels of certain selected conventional antimalarials 失效
    诱导某些选定的常规抗疟药物的快速治疗有效抗疟药水平的方法

    公开(公告)号：US4178376A

    公开(公告)日：1979-12-11

    申请号：US760859

    申请日：1977-01-21

    Applicant: Takeru Higuchi ,  Siegfried Lindenbaum

    Inventor： Takeru Higuchi ,  Siegfried Lindenbaum

    IPC: A61K47/12 ,  A61K31/47 ,  A61K9/42 ,  A61K31/135 ,  A61K31/44

    CPC classification number: A61K47/12

    Abstract: Rapid therapeutically effective antimalarial levels of a member selected from the group consisting of 6,8-Dichloro-.alpha.-(dibutyl-amino-methyl-2-(3',4'-dichlorophenyl-4-quinolinemethanol, 3-Dibutylamino-1-[2,6-bis(4-trifluoromethylphenyl)-4-pyridyl]propanol and 1,3-Dichloro-6-trifluoromethyl-9-[1-hydroxy-3-(dibutylamino) propyl]-phenanthrene are achieved by dissolving the same in an organic fatty acid of the formula: R-CCOH, wherein R represents a member selected from the group consisting of a saturated aliphatic hydrocarbon group of from seven to twenty carbon atoms and a mono-, di-, tri-, or tetra-unsaturated hydrocarbon group of from seven to twenty carbon atoms, and subsequently administering said acid containing the dissolved compound to a warm-blooded animal (e.g., human) afflicted with malaria.Because of the extremely poor solubility of the above-described antimalarial compounds, therapeutically effective antimalarial blood levels of the same have only been able to be achieved when such compounds are administered around the clock for extended periods of time. The method of this invention substantially enhances the bioavailability of these compounds and thus permits rapid therapeutically effective antimalarial blood levels of the same to be achieved.

    Abstract translation: 选自6,8-二氯-α-（二丁基 - 氨基 - 甲基-2-（3'，4'-二氯苯基-4-喹啉甲醇，3-二丁基氨基-1- [2,6-双（4-三氟甲基苯基）-4-吡啶基]丙醇和1,3-二氯-6-三氟甲基-9- [1-羟基-3-（二丁基氨基）丙基] - 菲是通过将其 在下式的有机脂肪酸中：R-CCOH，其中R表示选自7至20个碳原子的饱和脂族烃基和一 - ，二 - ，三 - 或四 - 7至20个碳原子的不饱和烃基，然后将含有溶解的化合物的所述酸施用于患有疟疾的温血动物（例如人），由于上述抗疟疾化合物的溶解度极差， 有效的抗疟血液水平只能达到 d当这些化合物长时间地全天候给药时。 本发明的方法基本上增强了这些化合物的生物利用度，因此可以实现其快速治疗有效的抗疟血液水平。

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