公开(公告)号：US4464363A

公开(公告)日：1984-08-07

申请号：US277291

申请日：1981-06-25

Applicant: Takeru Higuchi ,  Toshiaki Nishihata ,  Howard J. Rytting

Inventor： Takeru Higuchi ,  Toshiaki Nishihata ,  Howard J. Rytting

IPC: A61K9/02 ,  A61K31/625

CPC classification number: A61K9/02

Abstract: A method and drug form for enhancing the rate of absorption of a rectally administered drug from the rectal compartment into the blood stream of a warm blooded animal. The method includes the steps of preparing a drug form capable of being rectally administered. The drug form comprises a therapeutically effective unit dosage amount of a selected drug of the type which is capable of being absorbed into the blood stream from the rectal compartment and hydroxy aryl or hydroxy aralkyl acids or salts, amides or esters thereof, the hydroxy aryl or hydroxy aralkyl acids or salts, amides or esters thereof being present in the drug form in a sufficient amount to be effective in enhancing the drug absorption rate, when rectally administering the drug form to warm blooded animals.

Abstract translation: 一种用于增加直肠给药的药物从直肠隔室吸收到温血动物血液中的速率的方法和药物形式。 该方法包括制备能够被直肠给药的药物形式的步骤。 药物形式包含治疗有效单位剂量的所选药物，其能够被吸收到来自直肠隔室的血流中，羟基芳基或羟基芳烷基酸或其盐，酰胺或酯，羟基芳基或 羟基芳烷基酸或其盐，酰胺或酯以足够的量存在于药物形式中，以在将药物形式直接给予温血动物时有效提高药物吸收速率。

公开(公告)号：US4439196A

公开(公告)日：1984-03-27

申请号：US359447

申请日：1982-03-18

Applicant: Takeru Higuchi

Inventor： Takeru Higuchi

IPC: A61K9/00 ,  A61K9/22

CPC classification number: A61K9/0004

Abstract: An osmotic drug (or other beneficial substance) delivery system comprises a multi-chamber compartment formed by an external shell and one or more chamber-dividing walls each with a small orifice, of a microporous material and overlayers of semipermeable membranes completely covering the outer shell of all but one chamber and substantially covering the outer shell of the remaining chamber. Osmotic agents, adjuvants, enzymes, drugs, pro-drugs, pesticides and the like are incorporated in the chambers covered by the semipermeable membrane, and external fluids that diffuse into those chambers form solutions and by osmotic pressure are forced through the orifice to the drug chamber to form a solution thereof and then through the exposed microporous shell to the exterior of the device at a rate controlled by the permeability of the semipermeable overlay and the osmotic pressure gradient across the shell.

Abstract translation: 渗透药物（或其他有益物质）递送系统包括由外壳和一个或多个腔室分隔壁形成的多室隔室，每个隔室具有小孔，微孔材料和半透膜覆盖层完全覆盖外壳 除了一个室之外，并且基本上覆盖剩余室的外壳。 渗透剂，佐剂，酶，药物，前药，农药等掺入由半透膜覆盖的腔室中，并且扩散到这些腔室中的外部流体形成溶液并且渗透压力被迫通过孔口至药物 室以形成其溶液，然后以暴露的微孔壳体以由半透膜覆盖层的渗透性和穿过壳体的渗透压梯度控制的速率通过暴露的微孔壳体到达外部。

公开(公告)号：US4406896A

公开(公告)日：1983-09-27

申请号：US277444

申请日：1981-06-25

Applicant: Takeru Higuchi ,  Toshiaki Nishihata ,  Howard J. Rytting

Inventor： Takeru Higuchi ,  Toshiaki Nishihata ,  Howard J. Rytting

IPC: A61K9/02 ,  A61K31/40 ,  A61K31/43 ,  A61K31/545 ,  A61K47/12 ,  A61K47/20 ,  A61K31/425 ,  A61K31/54 ,  A61K31/625

CPC classification number: A61K47/20 ,  A61K31/40 ,  A61K31/43 ,  A61K31/545 ,  A61K47/12 ,  A61K9/02 ,  Y10S514/966

Abstract: A method and drug form for enhancing the rate of absorption of a rectally administered drug from the rectal compartment into the blood stream of a warm blooded animal. The method includes the steps of preparing a .beta.-lactam drug form capable of being rectally administered. The drug form comprises a therapeutically effective unit dosage amount of a selected drug of the type which is capable of being absorbed into the blood stream from the rectal compartment and hydroxy aryl or hydroxy aralkyl acids or salts, amides or esters thereof, the hydroxy aryl or hydroxy aralkyl acids or salts, amides or esters thereof being present in the drug form in a sufficient amount to be effective in enhancing the drug absorption rate, when rectally administering the drug form to warm blooded animals.

Abstract translation: 一种用于增加直肠给药的药物从直肠隔室吸收到温血动物血液中的速率的方法和药物形式。 该方法包括制备能够被直肠给药的β-内酰胺药物形式的步骤。 药物形式包含治疗有效单位剂量的所选药物，其能够被吸收到来自直肠隔室的血流中，羟基芳基或羟基芳烷基酸或其盐，酰胺或酯，羟基芳基或 羟基芳烷基酸或其盐，酰胺或酯以足够的量存在于药物形式中，以在将药物形式直接给予温血动物时有效提高药物吸收速率。

公开(公告)号：US4285947A

公开(公告)日：1981-08-25

申请号：US113313

申请日：1980-01-18

Applicant: Takeru Higuchi ,  Anand C. Burman

Inventor： Takeru Higuchi ,  Anand C. Burman

IPC: C07D213/48 ,  A61K31/11 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4409 ,  A61K31/505 ,  A61K31/519 ,  A61P3/00 ,  A61P7/10 ,  A61P9/12 ,  C07C47/02 ,  C07C47/14 ,  C07D475/08

CPC classification number: C07D475/08 ,  Y10S514/87

Abstract: The invention provides novel aldehyde adducts of triamterene having improved solubility and bioavailability as compared to triamterene. Pharmaceutical compositions containing the novel adducts and having diuretic activity are also described.

Abstract translation: 与Triamterene相比，本发明提供具有改善的溶解度和生物利用度的三氯乙烯的新型醛加合物。 还描述了含有新加成物并具有利尿活性的药物组合物。

公开(公告)号：US4252790A

公开(公告)日：1981-02-24

申请号：US517151

申请日：1974-10-23

Applicant: Takeru Higuchi

Inventor： Takeru Higuchi

IPC: A61K31/74 ,  A61K33/00

CPC classification number: A61K31/74 ,  A61K33/00

Abstract: Gastric ulcer-prone patients are treated by introducing into the stomach thereof an effective amount of a non-toxic, non-absorbable active agent, preferably an anion exchange resin having strong hydrophobic binding tendencies (e.g., a styrene-divinylbenzene copolymer bearing quaternary ammonium functional groups), or a hydrophobic, nonionic polymeric adsorbent, capable of effectively binding free and conjugated bile acids present in the stomach as a result of duodenogastric regurgitation.

Abstract translation: 通过向胃中引入有效量的无毒，不可吸收的活性剂，优选具有强疏水结合倾向的阴离子交换树脂（例如，带有季铵功能的苯乙烯 - 二乙烯基苯共聚物）来治疗胃溃疡易发患者 基团）或疏水性非离子聚合物吸附剂，其能够有效地结合由于十二指肠胃反流而存在于胃中的游离和结合的胆汁酸。

公开(公告)号：US4034756A

公开(公告)日：1977-07-12

申请号：US666365

申请日：1976-03-12

Applicant: Takeru Higuchi ,  Harold M. Leeper

Inventor： Takeru Higuchi ,  Harold M. Leeper

IPC: A01G7/06 ,  A61D7/00 ,  A61K9/00 ,  B01J4/04 ,  B65D1/04 ,  A61M5/00 ,  A61F5/46 ,  A61M31/00

CPC classification number: B01J4/04 ,  A01G7/06 ,  A61D7/00 ,  A61K9/0004 ,  B65D1/04

Abstract: An osmotically driven fluid dispenser for use in an aqueous environment comprising: a shape retaining canister having controlled permeability to water; an osmotically effective solute confined in the canister which, in solution, exhibits an osmotic pressure gradient against the water in the environment; an outlet in the canister wall; and a flexible bag of relatively impervious material that holds the fluid to be dispensed and is housed in the canister with its open end in sealed contact with the canister such that the canister outlet communicates with the bag interior and the bag interior is closed to the solute and aqueous solution thereof with the remainder of the bag spaced from and generally unsupported by the canister wall.

Abstract translation: 一种用于水性环境的渗透驱动的流体分配器，包括：具有受控的水渗透性的形状保持罐; 限制在罐中的渗透有效溶质，其在溶液中表现出对环境中的水的渗透压梯度; 罐壁上的出口; 以及保持要分配的流体的相对不透水材料的柔性袋，并且其容纳在罐中，其开口端与罐密封接触，使得罐出口与袋内部连通并且袋内部关闭到溶质 其水溶液与袋的其余部分间隔开并且通常不被罐壁支撑。

公开(公告)号：US3995632A

公开(公告)日：1976-12-07

申请号：US510753

申请日：1974-09-30

Applicant: Masahiro Nakano ,  Takeru Higuchi ,  Anwar Hussain

Inventor： Masahiro Nakano ,  Takeru Higuchi ,  Anwar Hussain

IPC: A61K9/00 ,  B01J4/04 ,  A61M31/00

CPC classification number: B01J4/04 ,  A61K9/0004

Abstract: An osmotic dispenser is described which is capable of releasing to its outside environment concentrations of active agent at an osmotically controlled rate over a prolonged period of time, and the active agent formulation of which is a solid or semisolid at storage temperatures, advantageously room temperature, and is fluid at the temperature of the prospective situs for the osmotic dispenser, typically at body temperature.

Abstract translation: 描述了一种渗透分配器，其能够在更长的时间内以渗透控制的速率释放其外部环境浓度的活性剂，并且其活性剂配方在储存温度，有利于室温下为固体或半固体， 并且在渗透分配器的预期位置的温度下是流体，通常在体温下。

公开(公告)号：US3968245A

公开(公告)日：1976-07-06

申请号：US573468

申请日：1975-05-01

Applicant: Takeru Higuchi

Inventor： Takeru Higuchi

IPC: A61K9/00 ,  A61K47/10 ,  A61K31/135 ,  A61K31/045 ,  A61K47/00

CPC classification number: A61K9/0014 ,  A61K47/10 ,  Y10S514/946

Abstract: Dermal compositions are disclosed with comprise trichloroethanol or trifluoroethanol as one component of a vehicle having solubilized therein a drug or other beneficial chemical compound. Also disclosed is a method for administering a drug or other beneficial chemical compound to the body which comprises contacting the skin with the drug or compound in the presence of trichloroethanol or trifluoroethanol which acts as an absorption promoter to enhance the topical or percutaneous absorption of the active drug or compound.

Abstract translation: 公开了包含三氯乙醇或三氟乙醇作为其中溶解有药物或其它有益化合物的载体的一种成分的皮肤组合物。 还公开了一种向身体施用药物或其它有益化学化合物的方法，其包括在三氯乙醇或三氟乙醇的存在下使皮肤与药物或化合物接触，其作为吸收促进剂，以增强活性物质的局部或经皮吸收 药物或化合物。

公开(公告)号：US3935196A

公开(公告)日：1976-01-27

申请号：US463092

申请日：1974-04-22

Applicant: Takeru Higuchi ,  Nicolae S. Bodor ,  Yu-Neng Kuo

Inventor： Takeru Higuchi ,  Nicolae S. Bodor ,  Yu-Neng Kuo

IPC: A61K31/52 ,  C07D473/08

CPC classification number: A61K31/52 ,  C07D473/08 ,  Y10S514/826

Abstract: There is provided novel and useful pro-drug forms of theophylline having the formula: ##SPC1##Wherein R represents a member selected from the group consisting of a straight or branched C.sub.4 -C.sub.20 alkyl group, a straight or branched C.sub.4 -C.sub.20 alkenyl group, a substituted phenyl group of a substituted or unsubstituted naphthyl group whose substituents are selected from the group consisting of a hydroxy group, a C.sub.1 -C.sub.4 alkyl group, a C.sub.1 -C.sub.4 alkoxy group, a C.sub.1 -C.sub.4 acyloxy group, and a halogen atom (Cl, Br, I), and a substituted or unsubstituted heteroaromatic group whose substituents are selected from the group consisting of a hydroxy group, a C.sub.1 -C.sub.4 alkyl group, a C.sub.1 -C.sub.4 alkoxy group, a C.sub.1 -C.sub.4 acyloxy group, and a halogen atom (Cl, Br, I), and wherein A represents a member selected from the group consisting of a --CO-- group, a --CO--(CH.sub.2).sub.n --CO-- group, wherein n represents an integer of from 1 to 16, a --CO--CH=CH--CO-- group (cis or trans), a ##SPC2##Group, and a ##SPC3##Group.The compounds of this invention are useful in the treatment of asthma in warm-blooded animals. Upon administration, the compounds of this invention slowly go into solution and subsequently cleave prior to and/or during the absorption process, releasing theophylline in a sustained manner at a non-toxic, therapeutic level; that is, without the large blood level variations normally observed when theophylline per se is administered.

Abstract translation: 提供了具有下式的茶碱的新颖有用的前药形式：

公开(公告)号：US4845233A

公开(公告)日：1989-07-04

申请号：US96092

申请日：1987-09-11

Applicant: Takeru Higuchi, deceased ,  by Kenji W. Higuchi, co-executor ,  Ooi Wong

Inventor： Takeru Higuchi, deceased ,  by Kenji W. Higuchi, co-executor ,  Ooi Wong

IPC: C07D233/70

CPC classification number: C07D233/70

Abstract: A compound having the formula: ##STR1## wherein R, R.sub.1 and R.sub.2 are independently selected from hydrogen; hydroxy; fluorine; bromine; chlorine; C.sub.1 -C.sub.20 alkyl; C.sub.2 -C.sub.20 alkenyl; C.sub.2 -C.sub.20 alkynyl; C.sub.3 -C.sub.10 cycloalkyl; C.sub.2 -C.sub.20 (monohydroxy or polyhydroxy)alkyl; C.sub.1 -C.sub.20 (monohalo or polyhalo)alkyl; carboxy; C.sub.1 -C.sub.20 alkylcarboxy; C.sub.1 -C.sub.20 alkenylcarboxy; C.sub.1 -C.sub.20 carboxyalkyl; C.sub.1 -C.sub.20 alkanoyl; C.sub.1 -C.sub.20 alkanoyloxy; C.sub.1 -C.sub.20 alkoxycarbonyl; carbamoyl; carbamyl; C.sub.1 -C.sub.20 alkylcarbamyl; sulfo; C.sub.1 -C.sub.20 alkylsulfonyl; C.sub.1 -C.sub.20 alkylsulfinyl; C.sub.1 -C.sub.20 alkylsulfoxide; C.sub.1 -C.sub.20 alkylsulfone; thio; C.sub.1 -C.sub.20 alkylthio; amino; nitro; C.sub.1 -C.sub.20 alkylamino; C.sub.1 -C.sub.20 aminoalkyl; substituted or unsubstituted phenyl or benzyl, the substituents being selected from hydroxy, fluorine, bromine, chlorine, C.sub.1 -C.sub.20 alkyl, C.sub.2 -C.sub.20 alkenyl, C.sub.2 -C.sub.20 (monohydroxy or polyhydroxy)alkyl, X is methyl or oxygen and n is 0 to 20. The invention is also directed to a method for increasing the topical penetration of a physiologically active agent across the skin or membrane of a mammalian organism. Also claimed is a pharmaceutical composition and a novel method for preparing 1-substituted-4-imidazolin-2-one.

Abstract translation: 具有下式的化合物：其中R，R 1和R 2独立地选自氢; 羟基; 氟; 溴; 氯; C 1 -C 20烷基; C2-C20烯基; C2-C20炔基; C3-C10环烷基; C2-C20（单羟基或多羟基）烷基; C 1 -C 20（单卤代或多卤代）烷基; 羧基; C 1 -C 20烷基羧基; C1-C20烯基羧基; C 1 -C 20羧基烷基; C1-C20烷酰基; C1-C20烷酰氧基; C1-C20烷氧基羰基; 氨基甲酰基; 氨基甲酰 C1-C20烷基氨基甲酰基; 磺基 C 1 -C 20烷基磺酰基; C1-C20烷基亚磺酰基; C1-C20烷基亚砜; C1-C20烷基砜; 硫代 C 1 -C 20烷硫基; 氨基; 硝基 C1-C20烷基氨基; C1-C20氨基烷基; 取代或未取代的苯基或苄基，取代基选自羟基，氟，溴，氯，C 1 -C 20烷基，C 2 -C 20烯基，C 2 -C 20（单羟基或多羟基）烷基，X为甲基或氧，n为0至 本发明还涉及增加生理活性剂穿过哺乳动物生物体的皮肤或膜的局部渗透的方法。 还要求保护的是药物组合物和制备1-取代-4-咪唑啉-2-酮的新方法。