著者

大坪 健児

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.120, no.11, pp.1135-1147, 2000-11-01 (Released:2008-05-30)

参考文献数

41

被引用文献数

1 2

---

This review summarizes our recent findings in the syntheses of drug metabolites. The metabolites of Grepafloxacin (1) and OPC-14117 (10) were prepared from the common intermediates (5) and (21), respectively. Moreover, treatment of 10 with a model P450 system led to a benzyl alcohol derivative (11) in one step. OPC-31260 (22) was efficiently N-dealkylated using several metalloporphyrins with oxidants to afford three metabolites (23-25). In addition, I succeeded in obtaining the metabolite (23) in high yield from N-oxide (26) not only as an oxygen donor but also as a substrate, there after, in the model P450 system. Optically active metabolites of OPC-29030 (27) were prepared by enzyme-catalyzed enantioselective transesterification of racemic sulfinyl metabolites. On the other hand, a chiral 1, 1'-bi-2-naphthol derivative (38a) was found to be an efficient asymmetric acylating agent for a secondary alcohol (36) which is a valuable intermediate for preparing optically active metabolites of 22. Furthermore, metabolites (45) and (47) of OPC-21268 (44) were prepared using SmI2-induced cyclization and oxidative decarboxylation with Pb(OAc)4 as key steps, respectively.

著者

黒田 宏紀 藤田 俊郎 宮寺 彰彦 金内 徹

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.110, no.8, pp.547-554, 1990-08-25 (Released:2008-05-30)

参考文献数

10

被引用文献数

2 1

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Cetraxate hydrochloride (1) (antiulcer agent) can be produced by the enzymatic debenzylation of cetraxate benzyl ester hydrochloride (2). In order to use the enzymatic method as an industrial procedure, it is essential to obtain the crystal of cetraxate (3, free compound of 1) as an intermediate from the enzymatic reaction solution. Cetraxate (3) was found to have four polymorphic forms, two anhydrides (A, B) and two hydrates (dihydrate I, II). It is very important for the practical procedure that cetraxate (3) crystal forms transform from the light crystal form (dihydrate I) to the heavy one (dihydrate II) in the enzymatic reaction solution. The transformation was strongly prevented by the cetraxate related substance, tranexamic acid-cetraxate hydrochloride condonsate (TS-1). The heavy crystal forms (dihydrate II, anhydride B) are thermodynamically more stable than the light one (dihydrate I). Crystal forms of 3 are stabilized as dihydrate II in water below 29°C and as anhydride B over 29°C.

著者

木内 祐二 増田 豊 亀井 大輔 向後 麻里 中村 明弘

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.133, no.2, pp.231-241, 2013-02-01 (Released:2013-02-01)

参考文献数

4

被引用文献数

3 4

---

In Showa University School of pharmacy, 7 competencies for outcome-based education were set up in 2011. We are now creating sequential curriculum in order to achieve these competencies. As a member of team medical treatment, pharmacist must share a patient's information with other members, assess each patient's condition, propose the best medication with evidence, and also check the effect of medication. Therefore, many active practices in a hospital and community and problem-based learning (PBL) tutorials are carried out in curriculum in School of Pharmacy. As a training for the future pharmacists who positively perform primary care with responsibility in community pharmacy, students study the method of clinical assessment (assessment of condition of disease from the patient's complain, and choice of appropriate proposal). Furthermore, the exercise and training of parenteral medication, physical assessment, and first aid, etc. are also taken in the curriculums as new clinical skill. The systematic and gradual interprofessional education curriculum for the team medical education has been carried out aiming at training of active members in medical team in a hospital and community. At this symposium, I will introduce these systematic advanced curriculums for the pharmacist of a new age, and to show the usefulness and learning effect.

著者

佐藤 英治

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.3, pp.345-347, 2015-03-01 (Released:2015-03-01)

参考文献数

2

被引用文献数

1 2

---

The third advanced workshop of the Pharmaceutical Society of Japan for pharmaceutical teachers was held from October 12th to 14th, 2013, and participants discussed an outcome-based approach to curriculum development in pharmacy education. In this article, I report the outcome-based spiral curriculum model of group 2A, which was designed to enable pharmacy students to understand a patient's condition, and to provide a basic practical ability in medical therapy. In the curriculum, pharmacy students will learn biochemistry and functional morphology in the first and second years, skills to interview patients in the third year, pathophysiology and pharmacotherapeutics in the third and fourth years, skills to estimate patient disease from physical examination in the fourth year, and practice in understanding real patient conditions in a clinical clerkship in the fifth year. The curriculum also included learning and evaluation methods.

著者

真野 高司

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.133, no.1, pp.67-72, 2013-01-01 (Released:2013-01-01)

参考文献数

6

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In order to successfully apply drug delivery systems (DDS) to new chemical entities (NCEs), collaboration between medicinal chemists and formulation scientists is critical for efficient drug discovery. Formulation scientists have to use ‘language’ that medicinal chemists understand to help promote mutual understanding, and medicinal chemists and formulation scientists have to set up strategies to use suitable DDS technologies at the discovery phase of the programmes to ensure successful transfer into the development phase. In this review, strategies of solubilisation formulation for oral delivery, inhalation delivery, nasal delivery and bioconjugation are all discussed. For example, for oral drug delivery, multiple initiatives can be proposed to improve the process to select an optimal delivery option for an NCE. From a technical perspective, formulation scientists have to explain the scope and limitations of formulations as some DDS technologies might be applicable only to limited chemical spaces. Other limitations could be the administered dose and, cost, time and resources for formulation development and manufacturing. Since DDS selection is best placed as part of lead-optimisation, formulation scientists need to be involved in discovery projects at lead selection and optimisation stages. The key to success in their collaboration is to facilitate communication between these two areas of expertise at both a strategic and scientific level. Also, it would be beneficial for medicinal chemists and formulation scientists to set common goals to improve the process of collaboration and build long term partnerships to improve DDS.

著者

糸川 秀治 竹谷 孝一 一柳 幸生 森田 博史

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.119, no.8, pp.529-583, 1999-08-01 (Released:2008-05-30)

参考文献数

149

被引用文献数

2 10

---

A lot of anticancer agents have been isolated from natural sources, especially from microorganisms and plants. However, there is no special type of compounds for cancer therapy. Various types of substances are effective for various types of cancers and tumors : for instance, alka1oids, lignans, terpenes and steroids, etc. In this report, the authors will describe especially about higher plants.

著者

平川 善行 原田 清

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.103, no.6, pp.690-695, 1983-06-25 (Released:2008-05-30)

参考文献数

5

被引用文献数

2 2

---

In the previous paper, a new technique for particle size reduction of oxolinic acid (OA), a slightly soluble model drug having an acidic group in a molecule, by the crystallization through the neutralization of its alkaline solution in the presence of certain surfactant or polymer was described. The wet sieving method by the use of polycarbonate membrane filter for the evaluation of size reduction effect was also described. Various factors affecting the size reduction of OA were investigated in this paper. The results obtained were as follows ; manners of participation in various factors affecting the size reduction varied with OA concentration at crystallization, and in the case of 5 w/v% OA concentration, the influences of addition rate of hydrochloric acid solution, stirring rate, reaction temperature and concentration of hydrochloric acid were relatively low. Size reduction effects of various surfactants and polymers were investigated. All of them were effective, though differences were recognized in the extent of size reduction. It has been found that the establishment of optimal conditions to obtain the finest particles is enabled and moreover, there is a possibility to prepare the particle that have an optional particle size by regulating the various factors.

著者

平川 善行 原田 清

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.102, no.10, pp.951-959, 1982-10-25 (Released:2008-05-30)

参考文献数

26

---

When slightly soluble medicinal crystals are administered orally, their particle size is one of the important factors affecting the bioavailability. Therefore, it was attempted to develop a new technique of particle size reduction, in which the addition of surfactants or polymers at crystallization was examined. In order to evaluate the size reduction effect for oxolinic acid (OA), the wet sieving method was studied by the use of the polycarbonate memblane filter. This method consists of the following procedures : 1) sonication of suspension more than 10 min, 2) suction filtration of suspension after dilution, 3) measurement of the weight of the residue on each filter by the determination of OA, 4) plots of the cumulative weight of residues on a log-probability paper, followed by calculation of apparent geometric mean diameter on weight basis, 5) regulation of the volume of filtrate according to the particle size of microcrystallines. It was found that the new method studied enabled to evaluate the size reduction effect easily and accurately.

著者

小森 浩二 塙 由美子 山本 淑子 古前 竜平 山崎 裕己 中野 祥子 三田村 しのぶ 宮﨑 珠美 菊田 真穂 高田 雅弘 首藤 誠

出版者

公益社団法人 日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.133, no.8, pp.905-911, 2013

被引用文献数

2

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&nbsp;&nbsp;Loxoprofen (Loxonin^&reg;), an antipyretic painkiller, was approved as an over-the-counter (OTC) drug (Loxonin^&reg;-S) in January 2011. With regard to self-medication using OTC drugs, the information that pharmacists provide to consumers is very important. Although loxoprofen is a very versatile drug and can be used during breastfeeding, information regarding its mammary gland transfer is inadequate. In this study, we established a simple method to evaluate mammary transfer of drugs, and compared loxoprofen's mammary gland transfer with that of aspirin. Loxoprofen 12 mg/kg and aspirin 132 mg/kg was orally administered to mother mice (ddY), and blood and milk samples were collected. Twenty microliters of ethanol was added to the blood and milk samples (10 &mu;L), and the mixture was centrifuged for 15 min (12000 <i>g</i>); the supernatant was analyzed by high-performance liquid chromatography. Since aspirin was immediately metabolized, we analyzed salicylic acid concentrations. Maximum concentration of loxoprofen was observed at around 15 min after its oral administration, with the concentrations in the blood and milk being 2.9 and 0.5 &mu;g/mL, respectively. The drug was metabolized promptly thereafter. In contrast, maximum concentration of salicylic acid was observed at 30 min after aspirin administration, with the concentrations in the blood and milk being 187.2 and 64.4 &mu;g/mL, respectively. These concentrations remained constant from 60 to 120 min. Salicylic acid could be detected 240 min after aspirin administration. Thus, mammary gland transfer of loxoprofen is lower than that of aspirin, suggesting that loxoprofen does not accumulate in milk.<br>

著者

桑田 一夫

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.132, no.8, pp.873-879, 2012 (Released:2012-08-01)

参考文献数

17

被引用文献数

1

---

We developed a theoretical framework for the regulation of biological macromolecules using the logically designed compounds. According to the cohomology theory, algebraic objects can be translated into geometrical ones. Successfully established quantum theory at 20th century, which essentially deals with the non-commutative nature of the space, also suggests the non-commutative topology of biological space. Arithmetic geometrical representation of the molecules as well as the macroscopic membranous structures would uncover their structural groups in Hilbert space. In order to construct the concrete image of biological space, here we combined quantum chemical (QC) model, all-atom (AA) model and coarse grained (CG) model, into one program designated ‘NAGARA’. These three models can be arranged in an arbitrary manner to yield the desired statistical ensemble. For example, QC model was applied to the optimization of the chemical structure of anti-prion lead compound GN8. Arithmetic geometrical representation of these algebraic models is in progress.

著者

濵田 芳男

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.133, no.10, pp.1113-1120, 2013-10-01 (Released:2013-10-01)

参考文献数

23

被引用文献数

1 1

---

This review discusses the importance of quantum chemical interactions in biomolecules for medicinal science and their relevance to the author's β-secretase (BACE1) inhibitor drug discovery research. Although molecular mechanics/dynamics (MM/MD) methods are available in many in silico design tools used for drug discovery, they cannot accurately evaluate quantum effects between biomolecules and drugs. The key roles of biomolecular quantum chemical interactions in drug discovery are discussed using the arginine side chain as an example. Arginine is recognized as a charged amino acid in commonly used drug design software, unlike other amino acids with π-electron orbitals, such as phenylalanine, tyrosine, and tryptophan. Quantum chemical interactions via the arginine side chain are crucial for molecular recognition, and are found in many X-ray crystal structures, such as protein-protein, protein homodimer, RNA aptamer-protein, and enzyme-inhibitor complexes. This review describes the essential role of quantum chemical interactions via the arginine side chain in the mechanism of BACE1 inhibition, and proposes an “electron donor/acceptor bioisostere” concept for medicinal science based on quantum chemical interactions. Several potent BACE1 inhibitors, as well as the first peptides with BACE1 inhibiting activity were designed and synthesized based on studies of quantum chemical interactions via arginine side chain and the “electron donor bioisostere” concept.

著者

中村 和則 城村 綾子 織田 実 猪 好孝 内山 浩之 大谷 尚也 宮崎 裕行 来海 正輝 秋澤 有四郎 岡 俊範

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.115, no.3, pp.201-212, 1995-03-25 (Released:2008-05-30)

参考文献数

28

被引用文献数

3 7

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Inhibitory activities of FUT-187 on trypsin-like serine proteases were compared using camostat mesilate (camostat), and 4-(4-guanidino benzoyloxy)-phenyl acetic acid methanesulfonate (GBPA) known as an active metabolite of camostat in the blood. Ki values of FUT-187 on the competitive inhibition mechanism were 0.097 μM for trypsin, 0.029 μM for pancreatic kallikrein, 0.61 μM for plasma kallikrein, 0.57 μM for plasmin, 2.5 μM for thrombin, 20.4 μM for factor Xa and 6.4 μM for Clr. However, FUT-187 acted as a noncompetitive inhibitor for factor XIIa and an uncompetitive inhibitor for Cls, and Ki values for these proteases were 0.021 and 0.18 μM, respectively. Ki values of camostat for these proteases were in the range of 0.037 to 96.4 μM, and those of GBPA for the above proteases except trypsin and plasma kallikrein were higher than those of FUT-187. The inhibitory activity of FUT-187 on trypsin was not reduced by the addition of the serum at 10%, whereas, that of GBPA was reduced (4.3 fold) in terms of IC50 values. The concentration of FUT-187 required to double APTT (activated partial thromboplastin time) was 1.09 μM, while GBPA, by concentrations up to 1 mM failed to double APTT. The kinin formation by glandular kallikrein in the rat plasma was inhibited by FUT-187 with IC50 value of 0.024 μM, while camostat revealed no inhibition by concentrations up to 1 μM. The complement-mediated hemolyses in the classical and alternative pathways were also inhibited by FUT-187 with IC50 values of 0.17 and 3.5 μM, respectively, the corresponding values for camostat being 350 and 150 μM, respectively. It is concluded that FUT-187 is a potent and selective inhibitor of trypsin-like serine proteases, and its inhibitory activities are stronger than those of camostat on glandular kallikrein, factor XIIa and Cls in complement pathway.

著者

佐々木 信行 緑川 淳 荒川 勝雅

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.112, no.8, pp.544-550, 1992-08-25 (Released:2008-05-30)

参考文献数

8

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FUT-187 (I), 6-amidino-2-naphthyl 4-[(4, 5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate, is a new synthesized proteinase inhibitor. Decomposition kinetics and photoreactivity of I in aqueous solution were studied. In aqueous solution, I was hydrolyzed to its moieties, [4-(4, 5-dihydro-1H-imidazol-2-yl)amino] benzoic acid (IABA) and 6-amidino-2-naphthol (AN). The hydrolysis followed a pseudo-first order reaction. I was stable under acidic condition between pH 2 and pH 3 and decomposed by irradiation from xenon light to form IABA, AN and compound II. The structure of II was studied by nuclear magnetic resonance, infrared, mass and ultraviolet spectra and identification tests. It was shown that II was 6-amidino-2-hydroxy-1-naphthyl[4-(4, 5-dihydro-1H-imidazol-2-yl)amino]-phenyl ketone, benzophenone derivative, produced by photorearrangement reaction of I.

著者

多比良 和基 安田 行寛 新藤 恭司 三谷 鳴夫 赤沢 明

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.100, no.3, pp.272-279, 1980-03-25 (Released:2008-05-30)

参考文献数

19

被引用文献数

2 2

---

The biological fate of 4-butyl-4-(β-carboxypropionyloxymethyl)-1, 2-diphenyl-3, 5-pyrazolidinedione : suxibuzone (SB) was studied in rats and beagle dogs. Furthermore, the effects of SB on liver microsomal drug metabolizing enzyme systems in rats were compared with those of phenylbutazone (PB), after daily oral administration of SB or PB for 1 week. 1) The biological fate of SB was different in rats and dogs and in the former a sex difference was noted. 2) Liver microsomal drug metabolizing enzyme systems were induced especially in male. 3) No difference between the two drugs was noted. However, when a single oral dose of SB was administered, keeping the PB schedule the same as above, the plasma half-life of PB was markedly shortened and maximum plasma levels of metabolites were rapidly reached. These results suggest that the biological fate of SB was stimulated by the enhancement or induction of liver microsomal drug metabolizing enzyme systems due to PB and its metabolites after daily oral administration.

著者

新藤 恭司 安田 行寛 多比良 和基 三谷 鳴夫 神田 敦弘 赤沢 明

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.99, no.12, pp.1186-1200, 1979-12-25 (Released:2008-05-30)

参考文献数

20

被引用文献数

4 5

---

The biological fate of 4-butyl-4-(β-carboxypropionyl-oxymethyl)-1, 2-diphenyl-3, 5-pyrazolidinedione (Suxibuzone, SB) was compared with that of phenylbutazone (PB) in rats, rabbits, beagle dogs and rhesus monkeys. The results obtained were as follows ; 1) When SB was administered orally, the main metabolites in the plasma were PB, oxyphenbutazone (Oxy-PB) and γ-hydroxyphenylbutazone (γ-Hydroxy-PB) in all species, though species differences were observed in the maximum plasma levels of the respective metabolites. Only in dogs and monkeys, was a small amount of SB detected in the plasma during the early time of dosing. 2) The metabolites and their maximum levels in plasma after the administration of SB were almost identical with those observed after the administration of PB. 3) After administration of SB, the main metabolites found in urine were PB, Oxy-PB, γ-Hydroxy-PB and their conjugates in all species, while species differences were observed in the percent excreted. In the dogs and monkeys, urinary excretion as the form of SB and 4-hydroxymethylphenylbutazone (4-HM-PB) glucuronides was observed in small amount for 0-12 hours. 4) There were no significant differences in the metabolites and their excreted percent in urine between SB and PB administration. 5) Differences between male and female in maximum plasma levels of PB and γ-Hydroxy-PB and in urinary excreted percent of γ-Hydroxy-PB were observed only in rats. 6) Species differences were observed in esterase activity on SB in vitro. 7) SB was bound to the albumin fraction as in the case of PB, but its binding percent was about 1/2 lower than that of PB. 8) SB showed anti-edematous action on carrageenin-induced edema and its activity was almost similar to that of PB. Anti-edematous activity of Oxy-PB was weaker than that of SB and γ-Hydroxy-PB had no effect on its action.

著者

野田 敦子 野田 浩司 今村 孝史 小野 行雄 森田 美華 甲斐 麻美子 嶺 佐知子 後藤 茂

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.111, no.9, pp.499-503, 1991-09-25 (Released:2008-05-30)

参考文献数

16

被引用文献数

3 6

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Pentanthrene type heterocyclic compounds, which contain oxazole, isoxazole, oxadiazole, thiazole, isothiazole, thiadiazole or pyrrole ring as C-ring, and naphthalene, quinoline, isoquinoline or quinoxaline ring as A·B-ring, were prepared, and their monoamine oxidase (MAO) inhibitory activities were examined. As expected from our previous investigation on the structure-activity relationship of this series, most of them showed strong inhibitory potency to both MAO-A and MAO-B. However, a few indicated highly selective inhibition for either of MAO subtypes.

著者

小野 秀樹 岡村 真彩 福島 章紘

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.138, no.9, pp.1201-1215, 2018-09-01 (Released:2018-09-01)

参考文献数

82

被引用文献数

9

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The anti-influenza virus drug oseltamivir has been reported to have several pharmacological actions including blocking of nicotinic acetylcholine receptor channels and activation of the dopaminergic system. These pharmacological actions highly overlap those of amantadine, another anti-influenza virus drug authorized in Japan, and ester-type local anesthetics. Moreover, oseltamivir and amantadine can clinically induce similar adverse neuropsychiatric reactions. In the present study, from the database of the Pharmaceuticals and Medical Devices Agency (PMDA), we surveyed 2576 drugs for which neuropsychiatric side effects similar to those of oseltamivir, amantadine and local anesthetics (abnormal behavior, confusion, consciousness disturbance, convulsion, delirium, delusion, hallucination, myoclonus, tremor) are listed as “clinically significant adverse reactions”, and found 327 that had at least one of these adverse reactions. Other neuraminidase inhibitors (laninamivir, peramivir and zanamivir) did not elicit such adverse reactions. By discussing the pharmacological effects of drugs that elicit these adverse reactions, we propose that the similarity of adverse neuropsychiatric reactions between oseltamivir and amantadine is possibly attributable to their common pharmacological effects.

著者

金沢 貴憲

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.138, no.4, pp.443-450, 2018-04-01 (Released:2018-04-01)

参考文献数

13

被引用文献数

6

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In general, the blood-brain barrier (BBB) poses a major challenge to drug development efforts targeting brain/central nervous system (CNS) diseases, since it limits the distribution of systemically administered therapeutics to the brain/ CNS. Therefore, the development of effective strategies for enhancing drug delivery to the brain has been a topic of great interest in both the clinical and pharmaceutical fields. Intranasal administration has been noted as a method for noninvasive delivery of a drug to the brain/CNS by bypassing the BBB via the “nose-to-brain” route. This nose-to-brain delivery system has the potential to be highly versatile, and a combination of this system with new drugs and siRNA shows promise in the treatment of CNS diseases. Cell-penetrating Tat peptide-modified block copolymer micelles have the potential for improving mucosal permeability and nose-to-brain transport efficiency. In addition, nano-sized drug carriers can improve nose-to-brain delivery through their ability to increase the stability of encapsulated drugs against biological degradation in the nasal cavity and brain/CNS. In this review, we introduce the assessment of and mechanisms for delivery to the brain after intranasal drug/siRNA administration with our cell-penetrating peptide-modified nano-sized polymer micelles. Our findings show that the use of polymer micelles with surface modification by cell-penetrating peptides for intranasal administration enables the noninvasive delivery of therapeutic agents to the brain/CNS by increasing the nose-to-brain transfer of the drug or siRNA administered from the nasal cavity.

著者

伊藤 邦彦

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.127, no.1, pp.43-53, 2007-01-01 (Released:2007-01-01)

参考文献数

18

被引用文献数

5 5

---

Phage display has been utilized for making recombinant antibody fragments (Fab or single chain Fv) of human, mouse, or other origins. After construction of an antibody combinatorial library, antigen-specific recombinant antibody fragments can be easily isolated by biopanning of the phage library displaying antibody fragment fused with viral coat protein III against antigen proteins, antigen-expressing live cells, or fixed cells. Using this technique, a variety of human recombinant antibody fragments can be retrieved from bone marrow cells, lymph node cells, or peripheral blood cells of patients with infectious diseases, autoimmune diseases, and cancer. To develop diagnostically and therapeutically useful human antibody medicines, we should first select recombinant antibody fragments not only with antigen-binding activity but also with bioactivity such as virus or toxin neutralization, or tumor-specific cytotoxicity. To achieve this goal, several steps in antibody phage display may be improved: 1) a larger library should be constructed for possible isolation of minor populations present in the repertoire; 2) the biopanning procedure should be improved for isolation of antibody fragments reactive with immunologically minor epitopes; 3) the screening procedure should be based on the measurement of the bioactivity as well as the antigen-binding activity; 4) if necessary, the affinity and specificity of selected antibody fragments should be improved. In this review, I discuss how to isolate clinically useful recombinant antibody fragments efficiently using a phage display system introducing our achievements.

著者

藤井 節郎 奥田 拓道 赤沢 明 安田 行寛 川口 安郎 福永 育史 西川 栄郎

出版者

公益社団法人日本薬学会

雑誌

薬学雑誌 (ISSN:00316903)

巻号頁・発行日

vol.95, no.6, pp.732-740, 1975

被引用文献数

5

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In order to investigate the fate of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) in comparison with that of 5-fluorouracil tritiated FT-207 (<SUP>3</SUP>H-FT-207) and 5-fluovouracil (<SUP>3</SUP>H-5-fluorouracil)were administered from the rectum in normal and AH-130 tumor-bearing rats, and rapid absorption of <SUP>3</SUP>H-FT-207 or <SUP>3</SUP>H-5-fluorouracil, was observed. Blood level of radioactivity after rectal administration of <SUP>3</SUP>H-FT-207 was higher and more continuous than that of <SUP>3</SUP>H-5-fluorouracil. Although the radioactivity after rectal administration of <SUP>3</SUP>H-FT-207 and <SUP>3</SUP>H-5-fluovouracil was widely distributed in the various tissues of the animal with or without tumor, the highest concentration of the radioactivity was observed in the kidneys, and higher in tumor. The radioactivity in lymphatic gland reached a maximum level within 2-4 hr after the rectal administration of <SUP>3</SUP>H-FT-207 and declined very slowly. The urinary excretion of radioactivity within 24 hr was about 30% of the administered dose of <SUP>3</SUP>H-FT-207. More than 85% of the excreted radioactivity accounted for FT-207 and its metabolite, &alpha;-fluoro-&beta;-alanine. Other metabolites such as 5-fluorouracil, &alpha;-fluoro-&beta;-ureidopropionic acid and tritiated water were detected in small amounts in rat urine. The radioactivity in blood and tumor, 4 hr after rectal administration of <SUP>3</SUP>H-FT-207, was found to represent FT-207. However, the radioactivity in liver was due to the presence of &alpha;-fluoro-&beta;-alanine. About 90% radioactivity in lymphatic gland within 2-6 hr after rectal administration of <SUP>3</SUP>H-FT-207 was detected as FT-207.