公开(公告)号：US4085214A

公开(公告)日：1978-04-18

申请号：US732979

申请日：1976-10-18

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

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

IPC: C07D473/08 ,  A61K31/52

CPC classification number: C07D473/08

Abstract: There is provided exceptionally stable and useful pro-drug forms of theophylline having the formula: ##STR1## wherein R represents a straight or branched phenylalkenyl group having 2-8 carbon atoms in the alkenyl portion.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: 提供特别稳定和有用的具有下式的茶碱的前药形式：其中R表示烯基部分中具有2-8个碳原子的直链或支链苯基烯基。

公开(公告)号：US4069307A

公开(公告)日：1978-01-17

申请号：US582353

申请日：1975-05-30

Applicant: Takeru Higuchi ,  Anwar Hussain

Inventor： Takeru Higuchi ,  Anwar Hussain

IPC: A61F6/14 ,  A61K9/00 ,  A61K9/26 ,  A61K9/70 ,  A61M31/00

CPC classification number: A61K9/7084 ,  A61F6/14 ,  A61F6/142 ,  A61K9/0004 ,  A61K9/0036 ,  A61K9/0039 ,  A61K9/0051 ,  A61M31/002

Abstract: Drug-delivery device for releasing a drug at a continuous and controlled rate for a prolonged period of time is comprised of a shaped body of polymeric material containing a pharmaceutically acceptable drug and permeable to passage of the drug by diffusion. The polymeric material is an ethylene-vinyl acetate copolymer having a vinyl acetate content of about 4 to 80% by weight and a melt index of about 0.1 to 1000 grams per 10 minutes.

Abstract translation: 用于以连续和受控的速率长时间释放药物的药物递送装置由含有药学上可接受的药物并且可透过药物通过扩散而可渗透的成形体的聚合材料构成。 聚合物材料是乙酸乙烯酯含量为约4-80重量％，熔体指数为约0.1-1000克/ 10分钟的乙烯 - 乙酸乙烯酯共聚物。

公开(公告)号：US3986510A

公开(公告)日：1976-10-19

申请号：US601154

申请日：1975-08-01

Applicant: Takeru Higuchi ,  Anwar A. Hussain ,  John W. Shell

Inventor： Takeru Higuchi ,  Anwar A. Hussain ,  John W. Shell

IPC: A61F9/00 ,  A61K9/00 ,  A61M31/00 ,  A61F5/46

CPC classification number: A61F9/0017 ,  A61K9/0051

Abstract: An ocular insert for the continuous controlled administration of a predetermined therapeutically effective dosage of drug to the eye over a prolonged period of time. The device meters the flow of drug by means of a drug release rate controlling material. The insert bioerodes in the environment of the eye concurrently with the dispensing or at a point in time after the dispensing of the therapeutically desired amount of drug.

公开(公告)号：US3962447A

公开(公告)日：1976-06-08

申请号：US603612

申请日：1975-08-11

Applicant: Takeru Higuchi ,  Nicolae S. Bodor ,  Efraim Shek

Inventor： Takeru Higuchi ,  Nicolae S. Bodor ,  Efraim Shek

IPC: C07D211/82 ,  A61K31/44

CPC classification number: C07D211/82

Abstract: There is provided, novel pro-drug forms of pyridinium aldoxime type cholinesterase reactivators, namely, dihydropyridinium aldoximes, having the formula: ##SPC1##Wherein R represents a member selected from the group consisting of an alkyl (C.sub.1 -C.sub.4) group, a ##SPC2##Group, a ##SPC3##Group, ##SPC4##Group, and a ##SPC5##Wherein Z represents a member selected from the group consisting of a --CH.sub.2 --CH.sub.2 -- group, a --CH.sub.2 --O--CH.sub.2 -- group, a --CH.sub.2 CH.sub.2 OCH.sub.2 CH.sub.2 -- group, and a --CH.sub.2 O--CH.sub.2 --CH.sub.2 --O--CH.sub.2 -- group; wherein R.sub.1 represents a member selected from the group consisting of a hydrogen atom, a methyl group, an acyl group and a ##EQU1## group; and wherein X.sup.- represents an anion derived from a pharmaceutically acceptable acid addition salt.These compounds are useful in reactivating cholinesterase, inhibited following exposure to and/or ingestion of conventional anti-cholinesterase agents, especially in the brain.

Abstract translation: 提供了吡啶鎓醛肟型胆碱酯酶再活化剂的新型前药形式，即二氢吡啶鎓醛肟，具有下式：

公开(公告)号：US3960150A

公开(公告)日：1976-06-01

申请号：US613384

申请日：1975-09-15

Applicant: Anwar A. Hussain ,  Takeru Higuchi ,  John W. Shell

Inventor： Anwar A. Hussain ,  Takeru Higuchi ,  John W. Shell

IPC: A61F9/00 ,  A61K9/00 ,  A61M31/00

CPC classification number: A61K9/0051 ,  A61F9/0017

Abstract: An ocular insert for the continuous controlled administration of a predetermined therapeutically effective dosage of drug to the eye over a prolonged period of time. The device meters the flow of drug by means of a drug release rate controlling material. The insert bioerodes in the environment of the eye concurrently with the dispensing or at a point in time after the dispensing of the therapeutically desired amount of drug.

公开(公告)号：US3950521A

公开(公告)日：1976-04-13

申请号：US580134

申请日：1975-05-23

Applicant: Takeru Higuchi ,  Anwar Hussain

Inventor： Takeru Higuchi ,  Anwar Hussain

IPC: A61K31/60 ,  A61K31/615

CPC classification number: A61K31/621 ,  A61K31/60

Abstract: Alkali and alkaline earth metal salts of salicylamide are administered in solid oral dosage forms with substantially improved analgesic, anti-inflammatory, antipyretic and sedative results as compared with salicylamide. Highest blood levels are obtained by administering enteric-coated salicylamide salt dosage forms.

Abstract translation: 与水杨酰胺相比，水杨酰胺的碱金属盐和碱土金属盐以固体口服剂型施用，具有显着改善的镇痛，抗炎，解热和镇静作用。 通过施用肠溶衣水杨酰胺盐剂型获得最高血液水平。

公开(公告)号：US4910314A

公开(公告)日：1990-03-20

申请号：US301843

申请日：1989-01-26

Applicant: Pierre M. R. de Montigny ,  Larry A. Sternson ,  Arnold J. Repta ,  John F. Stabaugh ,  Takeru Higuchi, deceased ,  by Martin B. Dickinson, Jr., co-executor ,  by Kenji W. Higuchi, co-executor

Inventor： Pierre M. R. de Montigny ,  Larry A. Sternson ,  Arnold J. Repta ,  John F. Stabaugh ,  Takeru Higuchi, deceased ,  by Martin B. Dickinson, Jr., co-executor ,  by Kenji W. Higuchi, co-executor

IPC: G01N33/52 ,  G01N33/68

CPC classification number: G01N33/52 ,  G01N33/6809

Abstract: There is provided a fluorescent adduct which is amenable to detection by fluorometric and electrochemical techniques. The adduct is of the formula: ##STR1## wherein X is a radical derived from a primary amine of the formula X--NH.sub.2 and where R.sub.1 --R.sub.6 are selected from various organic or inorganic substituents.

Abstract translation: 提供荧光加合物，其可以通过荧光和电化学技术进行检测。 加合物具有下式：其中X是衍生自式X-NH 2伯胺的基团，其中R 1 -R 6选自各种有机或无机取代基。

公开(公告)号：US4771004A

公开(公告)日：1988-09-13

申请号：US901732

申请日：1986-08-29

Applicant: Takeru Higuchi

Inventor： Takeru Higuchi

IPC: G01N13/00 ,  G01N33/15 ,  G01N33/50 ,  A61K35/58 ,  G01N7/10

CPC classification number: G01N33/5088 ,  G01N13/00 ,  G01N33/15 ,  Y10S424/07

Abstract: Provided is a novel barrier membrane and a method using the barrier membrane for testing the transdermal penetration behavior of a bioactive agent. The method employs shed snake skin as the model barrier membrane. In particular, the method comprises the steps of providing a dose of a donor formulation containing the bioactive agent, and a receptor solution, with a barrier membrane of shed snake skin separating the donor formulation and receptor solution. The receptor solution is then serially sampled and assayed in order to determine the concentration of the bioactive agent in the receptor solution. The use of the shed snake skin has been found to provide reproducible and uniform results as a model barrier membrane. As well, the shed snake skin offers the advantages of being readily available and storable for an extended period of time.

Abstract translation: 提供了一种新颖的屏障膜和使用阻隔膜来测试生物活性剂的透皮渗透行为的方法。 该方法采用脱皮蛇皮作为阻隔膜。 特别地，该方法包括以下步骤：提供含有生物活性剂的供体制剂剂量和受体溶液，其中分离供体制剂和受体溶液的脱落蛇皮的屏障膜。 然后对受体溶液进行连续取样和测定，以确定受体溶液中生物活性剂的浓度。 已经发现使用脱皮蛇皮提供可重复且均匀的结果作为模型阻隔膜。 此外，脱皮蛇皮也提供了长时间可用和可储存的优点。

公开(公告)号：US4762851A

公开(公告)日：1988-08-09

申请号：US802907

申请日：1985-11-29

Applicant: Jose Alexander ,  Takeru Higuchi

Inventor： Jose Alexander ,  Takeru Higuchi

IPC: A61K47/22 ,  A61K31/19 ,  A61K31/20 ,  A61K31/40

CPC classification number: A61K47/22 ,  A61K9/0014

Abstract: The invention relates to pyroglutamic acid esters used as dermal penetration enhancers for therapeutic agents having poor skin permeation.

公开(公告)号：US4758520A

公开(公告)日：1988-07-19

申请号：US837671

申请日：1986-03-10

Applicant: Bodgan Matuszewski ,  Richard S. Givens ,  Robert G. Carlson ,  Takeru Higuchi ,  Takao Kawasaki ,  Osborne S. Wong

Inventor： Bodgan Matuszewski ,  Richard S. Givens ,  Robert G. Carlson ,  Takeru Higuchi ,  Takao Kawasaki ,  Osborne S. Wong

IPC: G01N33/50 ,  C07C69/63 ,  C07D209/58 ,  C07D209/62 ,  C09K11/07 ,  G01N21/76 ,  G01N33/52 ,  G01N33/68 ,  G01N33/84

CPC classification number: G01N33/84 ,  G01N33/52 ,  G01N33/6809 ,  Y10T436/142222 ,  Y10T436/172307 ,  Y10T436/173845 ,  Y10T436/200833 ,  Y10T436/203332 ,  Y10T436/206664

Abstract: A chemiluminescence method for assaying compounds containing primary amino groups using 1-cyano-2-substituted benz(f)- or naphth(f)-isoindole fluorescers is disclosed. The 1-cyano-2-substituted benz(f)- or naphth(f)-isoindole (CBI or CNI) is formed by reacting a compound containing a primary amino group with naphthalene-2-3-dicarboxaldehyde or anthracene-2,3-dicarboxaldehyde in the presence of cyanide ion. The reaction product of hydrogen peroxide with an oxalate ester is then combined with the CBI or CNI to form an analyte which exhibits chemiluminescence. A detector is used to measure the chemiluminescence emission from the chemiluminescence derivatized analytes. Compounds containing primary amino groups which may be assayed according to the present invention include primary amines, amino acids, peptides and catecholamines. The method can also be adapted to the analysis of trace amounts of cyanide ion and hydrogen peroxide.

Abstract translation: 公开了使用1-氰基-2-取代的苯并（f） - 或萘（f） - 异吲哚荧光剂测定含有伯氨基的化合物的化学发光方法。 1-氰基-2-取代的苯并（f） - 或（f） - 异吲哚（CBI或CNI）是通过使含有伯氨基的化合物与萘-2,3-二甲醛或蒽-23 在氰化物离子存在下加入二甲醛。 然后将过氧化氢与草酸酯的反应产物与CBI或CNI组合以形成显示化学发光的分析物。 检测器用于测量化学发光衍生分析物的化学发光。 可以根据本发明测定的含有伯氨基的化合物包括伯胺，氨基酸，肽和儿茶酚胺。 该方法也可适用于痕量氰化物离子和过氧化氢的分析。