著者

田中 智之

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.477-486, 2018-04-01 (Released:2018-04-01)

参考文献数

23

被引用文献数

2

---

An increasing number of cases of research misconduct and whistle-blowing in the fields of medicine and life sciences has created public concern about research integrity. In Europe and the United States, there has been a large focus on poor reproducibility in life science research, and poor reproducibility is largely associated with research misconduct. Research integrity is equally crucial in the pharmaceutical sciences, which play an important role in medical and life sciences. Individual cases of research misconduct have not been investigated in detail in Japan, because it was generally believed that only researchers with strong or strange personalities would participate in misconduct. However, a better understanding of research misconduct will enable more in-depth discussions about research integrity, which is now known to be closely associated with normal research activities. Here I will introduce information on various contemporary activities being performed to create a sound research environment, drawn from practices in universities, pharmaceutical companies, and government agencies. I will also discuss ways in which individual researchers can promote research integrity.

著者

瀬川 林次郎

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.1915, no.401, pp.854-868, 1915-07-26 (Released:2018-08-30)

著者

西田 孝洋

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.129, no.8, pp.925-932, 2009-08-01 (Released:2009-08-01)

参考文献数

41

被引用文献数

1 1

---

Because it is difficult to achieve local drug activity following administration by the conventional intravenous and oral routes, I sought to develop a new route of administration utilizing drug absorption from the liver surface in order to target that organ. Although direct application to the liver surface should yield local drug distribution, drug absorption from the liver surface has not been reported in the literature. Therefore, we analyzed, as a model, the efficiency of absorption of several organic anions and dextrans of various molecular weights following application to the rat liver surface in vivo using a cylindrical diffusion cell. Each compound appeared gradually in the plasma, followed by excretion into the bile and/or urine, indicating the possibility of drug absorption from the liver surface. The absorption process from the liver surface may not involve a specific transport system because dose and transport inhibitors had no detectable effect. In addition, molecular weight was found to be a determinant of absorption through the liver surface. The efficiency of targeting desired region in the liver was enhanced considerably by application to the liver surface, compared to intravenous administration. Moreover, I have obtained several promising results from the application of this new drug delivery system to anticancer drugs and gene therapy. On the other hand, I have also clarified the characteristics of drug absorption from the surfaces of the kidney, stomach, cecum and small intestine, and plan to apply the physiological findings to other fields.

著者

恩田 光子 兼松 美和 北村 朋子 酒井 隆浩 阪上 久美子 田中 景子 濱畑 有記美 廣岡 輝子 藤井 貴和子 松田 雅史 三木 春奈 真下 博孝 羽田 理恵 荒川 行生

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.7, pp.1159-1166, 2007 (Released:2007-07-01)

参考文献数

10

被引用文献数

8 8

---

Access to drug information (DI) needed to evaluate generic product bioequivalence was studied to identify problems with the current status of DI availability and encourage proper use of DI. Ten items were chosen from among the stock of branded products at the University Pharmacy, and five corresponding generics were selected for each item. Conditions of access to information on pharmacokinetic tests and dissolution tests were rated and the assigned ratings compared. In the case of pharmacokinetic parameters obtainable from makers of generic drugs, we also performed Welch's t-test to compare the difference between values reported for branded and generic products. From the standpoint of individual tests, the pharmacokinetic tests yielded higher scores on the whole than did the dissolution tests, and low scores were obtained for the half-life of blood drug concentration (T1/2). We observed a tendency for the adequacy of information to depend more upon the drug item itself than upon the nature of the test. The percentage of tests allowing for comparison with branded products varied from 0%-75% (average 49%). Parameter by parameter, the range of variation was from 35% of Tmax to 63% of Cmax. Factors precluding comparison included insufficient data on branded products, mismatch in assayed chemical species between branded and generic, mismatch between final sampling time in AUCt measurement, dosage inconsistency, and insufficient data on generic products. DI should be provided in a manner that facilitates comparison of information supplied by generic drug makers with data released by makers of branded products.

著者

前野 哲博

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.137, no.7, pp.859-867, 2017-07-01 (Released:2017-07-01)

参考文献数

7

---

Due to the rapid aging of the population, it has become important to ensure the provision of primary health care services. To respond to this challenge, it will be insufficient to offer services only at medical institutions; indeed, there are extremely high expectations for pharmacists because they work in close contact with the population at drugstores and pharmacies. Moreover, the Japanese government intends to promote family pharmacies (pharmacists) that not only prepare drugs but also give advice on health issues. In this context, pharmacists are expected to play new roles that surpass those in the existing framework, and this will require a new program to facilitate the acquisition of new abilities (skill mix). As an example, we would like to introduce an education program for pharmacists designed to develop clinical reasoning skills for patients' symptoms. To care properly for patients with symptoms and to decide whether to encourage self-medication or to recommend consultation with a doctor, pharmacists need to develop the ability to take a medical history in a systematic and reasonable way, and then to make an adequate assessment. Therefore on the basis of cooperation between doctors and pharmacists, we have developed an education program, as well as a medical interview support tool to assist pharmacists in obtaining necessary and comprehensive medical histories.

著者

北川 勲 陳 兆隆 吉原 実 小林 勝也 吉川 雅之 小野 尚彦 吉村 祐次

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.104, no.8, pp.858-866, 1984-08-25 (Released:2008-05-30)

参考文献数

17

被引用文献数

10 16

---

The alkaloidal constituents of two types of "pao-fuzi ( ?? ?? ?? )", the processed tuber of Aconitum carmichaeli DEBX., were investigated. Aconitine (1), hypaconitine (2), mesaconitine (3), talatizamine (5), 14-acetyltalatizamine (6), isotalatizidine (7), karakoline (8), neoline (9), lipoaconitine (10), lipohypaconitine (11), lipomesaconitine (12), and lipodeoxyaconitine (13) were identified from"banshu-fuzi ( ?? ?? ?? ?? )", while benzoylaconine (1a), benzoylhypaconine (2a), and benzoylmesaconine (3a) together with 1-3, 5-9 were identified from"fupian ( ?? ?? )". By use of a dual-wavelength thin layer chromatography scanner, lipo-alkaloids (10-13) were shown to be distributed as major alkaloids in thirteen out of fifteen kinds of "fuzi"and wutou". It was also found that these lipo-alkaloids were less toxic as compared with the corresponding fatally toxic alkaloids such as 1 and 3. However, lipomesaconitine (12) was found to exhibit antiinflammatory and analgesic activities. It was suggested that the substitutions of the acetyl residues attached to the C-8 hydroxyls of 1-4 for the fatty acid residues were the other possible chemical modifications in the decrease of toxicities of Aconiti Tuber.

著者

木島 孝夫 高崎 みどり 小塚 睦夫 徳田 春邦

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.114, no.4, pp.248-256, 1994-04-25 (Released:2008-05-30)

参考文献数

27

被引用文献数

1 2

---

To search for possible anti-tumor promoters, we carried out a primary screening of fourteen kampo prescriptions utilizing their possible inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation which is induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). In these prescriptions, shouseiryu-to exhibited the most significant inhibitory effect on the EBV-EA activation. Furtheremore, two-stage carcinogenesis of mouse skin tumors induced by 7, 12-dimethylbenz [α] anthracene (DMBA) and TPA, and mouse pulmonary tumors induced by 4-nitroquinoline-N-oxide (4NQO) and glycerol were strongly inhibited by shouseiryu-to.

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

no.194, pp.361-367, 1898-04-26

著者

長谷川 栞 畠平 春奈 長沼 美紗 島内 あかり 笹岡 沙也加 元岡 佑美 福田 昌穂 阿部 純子 中尾 智史 加藤 大和 大森 智史 井口 和弘 中村 光浩

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.137, no.10, pp.1301-1311, 2017-10-01 (Released:2017-10-01)

参考文献数

36

被引用文献数

2 3

---

OTC drugs play an important role in self-medication. OTC analgesic and antipyretic drugs are widely used in Japan. The present study aimed to survey the components of OTC drug package inserts for analgesic and antipyretic drugs and to evaluate the adverse event profiles using the Japanese Adverse Drug Event Report database (JADER). The JADER contains 430587 reports from between April 2004 and November 2016; a total of 750 reports of adverse events resulted from the use of OTC analgesic and antipyretic drugs. The safety signals were detected by the reporting odds ratio (ROR). The ROR values for “Skin & subcutaneous tissue disorders”, “Immune system disorders”, and “Hepatobiliary disorders” stratified by system organ class of the Medical Dictionary for Regulatory Activities (MedDRA) were 7.58 (6.56-8.76), 4.25 (3.51-5.14), and 2.35 (1.93-2.85), respectively. OTC analgesic and antipyretic drugs containing allylisopropylacetylurea (AIAU) exhibited a significantly high reporting ratio of “Skin & subcutaneous tissue disorders” compared with the drugs without AIAU. No difference in the reported incidence of “Hepatobiliary disorders” was found between the drugs with or without acetaminophen. Our results suggested that it was important to monitor patients who use OTC analgesic and antipyretic drug containing AIAU; in particular, careful attention should be paid to skin and subcutaneous tissue disorders.

著者

畠山 史朗 鈴木 規子 安部 一弥 金野 昇 金子 俊幸 豊口 禎子 白石 正

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.8, pp.1095-1101, 2018-08-01 (Released:2018-08-01)

参考文献数

19

---

Chemotherapy-induced nausea and vomiting (CINV) is the most unbearable adverse effect of chemotherapy. The antiemesis guidelines of the National Comprehensive Cancer Network indicate that hyponatremia is a risk factor for CINV, although the relationship between the incidence of CINV and hyponatremia has not been sufficiently studied. This two-center prospective observational study evaluated whether low serum sodium concentrations were a risk factor for CINV. The study included 34 patients who were scheduled to receive first-line carboplatin- or oxaliplatin-based chemotherapy for gynecological or colorectal cancers. Patient diaries were used to record the daily incidences of CINV events during a 5-day period. The patients were divided based on the median serum sodium concentration into a low Na+ group (<141 mEq/L) and a high Na+ group (≥141 mEq/L). The incidences of delayed nausea were 27.8% in the high Na+ group and 62.5% in the low Na+ group (p=0.042), with complete control rates (no vomiting, rescue medication, or grade 2 nausea) of 77.8% and 43.8%, respectively (p=0.042). The time to complete control failure in each group was analyzed using the Kaplan-Meier method, which revealed a significantly shorter time in the low Na+ group (p=0.03). Therefore, these results indicate that low serum sodium concentrations may increase the risk of CINV.

著者

味澤 幸義 赤羽 健司 赤羽 増夫 佐藤 和明 玉井 哲郎 斉藤 勝 田中 信之 鎌田 晃爾 小林 通洋

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.116, no.9, pp.735-747, 1996-09-25 (Released:2008-05-30)

参考文献数

13

被引用文献数

1 1

---

A number of benzimidazole derivatives were synthesized and tested for cholecystokinin A (CCK-A) receptor inhibitory activity in order to study structure-activity relationships. Significant CCK-A receptor inhibitory activities were found in the compounds having carboxyl or tetrazolyl group. As the most preferred compound, 4-(5, 6-dichlorobenzimidazol-2-yl)-N-(3-methoxypropyl)-N-pentylglutaramic acid (4g) was selected.

著者

田中 洋和 中原 邦夫 畑中 洋 稲村 典昭 黒田 昭雄

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.117, no.8, pp.542-554, 1997-08-25 (Released:2008-05-30)

参考文献数

17

被引用文献数

7 19

---

Tacrolimus hydrate (FK506), a novel 23-membered macrolide, is an immunosuppressant isolated from Streptomyces tsukubaensis using extensive screening of fermentation products to identify a compound inhibiting the mixed lymphocyte reaction (MLR). The in vitro and in vivo immunosuppressive activities of FK506 were found to be more potent than those of cyclosporine (CyA). The superior immunosuppression with FK506 treatment was also confirmed in the skin allograft model in rats and liver transplantation in dogs. Clinical studies were initiated by Prof. Starzl at the University of Pittsburgh in 1989, and he demonstrated that FK506 surpassed CyA in the incidence of graft survival and the frequency of graft rejection. Multicenter randomized clinical studies, comparing FK506 to CyA corroborated the efficacy of FK506 on the survival of patients and of grafts, and especially on the appearance of severe refractory graft rejection. FK506 was marketed in 1993 in Japan, and was followed in 1994 in the U.S.A., U.K, and Germany. The mechanism of action of this compound was clarified by the endeavors of Prof. Schreiber, who demonstrated the existence of a binding protein for FK506 called FKBP, similar to cyclophilin for CyA. The FK506/FKBP complex binds with calcineurin, a serine/threonine phosphatase to inhibit the translocation of NFAT into the nucleus, resulting in inhibition of transcription of IL-2 mRNA. FK506 displays potent immunosuppressant activity, and contributes not only to the progress of transplantation therapy for clinical studies, but also to the clarification of signal transduction in T cell activation for basic science.

著者

長尾 康次 上田 聡 神田 宗和 大畑 暢敬 山下 道雄 日野 資弘

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.130, no.11, pp.1471-1478, 2010 (Released:2010-11-01)

参考文献数

10

被引用文献数

2 2

---

Natural fermentation products have long been studied as attractive targets for drug discovery due to their amazing diverse, complex chemical structures and biological activities. As such, a number of revolutionary drugs developed from natural fermentation products have contributed to global human health. To commercialize a drug derived from natural fermentation products, an effective chemical entity must be identified and thoroughly researched, and an effective manufacturing process to prepare a commercial supply must be developed. To construct such a manufacturing process for tacrolimus and micafungin, the following studies were conducted: first, we focused on controlling the production of the tacrolimus-related compound FR900525, a fermentation by-product of tacrolimus which was critical for quality assurance of the drug substance. FR900525 production was reduced by using a mutant strain which produced more pipecolic acid, the biosynthesis material of tacrolimus, than the original strain. Then, to optimize the fermentation process of FR901379, an intermediate of micafungin, a fed-batch culture was adopted to increase FR901379 productivity. Additionally, FULLZONETM impeller was installed into the scaled-up fermenter, reducing the agitation-induced damage to the mycelium. As a result, the mycelial form changed from filamentous to pellet-shaped, and the air uptake rate during fermentation was drastically improved. Finally, we conducted screening for FR901379 acylase-producing microorganisms, as FR901379 acylase is necessary to manufacture micafungin. We were able to easily discover FR901379 acylase-producing microorganisms in soil samples using our novel, convenient screening method, which involves comparing the difference in antibiotic activity between FR901379 and its deacylated product.

著者

長尾 善光

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.5, pp.401-427, 1982-05-25 (Released:2008-05-30)

参考文献数

55

被引用文献数

3 4

---

The auther has developed numerous new reactions utilizing sulfur-containing leaving groups and attempted to use them for the synthesis of biologically active natural products. As shown in Chart 2, the mode of elimination of the sulfur-containing leaving groups is classified into two types. In the first half of this review, a type 2 reaction, in which 3-acyl-1, 3-thiazolidine-2-thione is used as Y-[○!S]and an amine as the nucleophile, is outlined. In the latter half, its application is described. It is concerned with the total synthesis of macrocyclic spermidine alkaloids (codonocarpine, (±)-lunarine, and (±)-lunaridine), the peptide synthesis, the total synthesis of parabactin, a spermidine-containing siderophore, the synthesis of new hypoxic cell sensitizers, FNT-1 and FNT-2, and a new design for chiral induction to the prochiral a cyclic molecules.

著者

土谷 義己 森 昌斗 田口 胤三

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.96, no.4, pp.490-497, 1976-04-25 (Released:2008-05-30)

参考文献数

24

被引用文献数

3 5

---

To examine the effect of neighboring group on thermal treatment of O-alkyl S-methyl dithiocarbonates, syntheses of O-ethyl S-methyl dithiocarbonates holding alkyl (or aryl)-sulfinyl group were tried by the reaction of 2-alkyl (or aryl) sulfinylethanol and carbon disulfide in an aqueous sodium hydroxide followed by methylation with methyl iodide. However, the reaction did not progress as expected and gave 2-alkyl (or aryl) sulfinylethyl methyl trithiocarbonates (Va, -d) as main products. Nuclear magnetic resonance spectral data of these products suggested the formation of trithiocarbonate to occur via elimination and addition. It was thereby clarified that the alkyl (or aryl) sulfinyl as the neighboring group worked as an electron-attracting group to favor elimination.

著者

大沢 基保

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.129, no.3, pp.305-319, 2009 (Released:2009-03-01)

参考文献数

58

被引用文献数

17 25

---

Immunotoxic effects of heavy metals, as a typical environmental agent, and their mechanisms are reviewed based on our findings on autoimmune response induced by exposure to cadmium (Cd) as CdCl2. Adverse immune effects of chemicals, defined as immunotoxicity, have been used as a sensitive biomarker for assessing health effects of environmental chemicals. My initial research focused on renal toxicity of heavy metals was developed to elucidate characteristics and mechanisms for immune-mediated nephritis induced by heavy metals. In our studies the most interesting finding was autoantibody production enhanced by the oral exposure to Cd at environmental levels. It was observed simultaneously with enhancement of non-specific antibody production and suppression of primed-antigen specific antibody production. Immunostimulation including induction of autoantibodies was found to be the primary immunotoxic effect of Cd, because of the dose-sensitivity, and to be associated with polyclonal B cell activation (PBA). Further mechanism studies on the PBA induced by Cd in vitro showed that it was mediated by T cells, via cytokines, dominantly Type-2 cytokines, and recognition of MHC-II antigens of cell surface. The similarity among PBAs induced by inorganic salts of Cd, mercury and lead suggests that it would be the common effect among the metals to be involved in their pathogenesis of nephritis. Finally possible health significance of chemical-induced PBA is discussed associated with an increasing trend of autoimmune diseases in industrialized countries.

著者

永倉 正彦 岡本 敏彦

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.92, no.2, pp.167-175, 1972-02-25 (Released:2008-05-30)

参考文献数

15

被引用文献数

1 1

---

An addition-elimination reaction, which was reported in the reaction of 3-nitroquinoline with aqueous sodium hypobromite in methanolic KOH, also occurred in the case of other nitroquinolines, i.e., 6-, 5-, 8-, and 4-nitroquinolines. 6-Nitroquinoline (I) gave 6-bromo-5-methoxyquinoline (IIa), 6, 8-dibromo-5-methoxyquinoline (IIb), 6-bromo-5, 7-dimethoxyquinoline (IIIa), 5, 7-dimethoxy-6-nitroquinoline (IIIb), 8-bromo-5, 7-dimethoxy-6-nitroquinoline (IIIc), and 8-bromo-6-oxo-5, 5, 7-trimethoxy-5, 6-dihydroquinoline (IV) on being reacted in the same way as in the reaction of 3-nitroquinoline. Other nitroquinolines and their products from the same reaction were ; 5-nitroquinoline (XI); 5-bromo-6-methoxyquinoline (XIIa), 6-methoxy-5-nitroquinoline (XIIb), 8-methoxy-5-nitroquinoline (XIIIa), 5, 7-dibromo-6, 8-dimethoxyquinoline (XIVa), and 6, 8-dimethoxy-5-nitroquinoline (XIVb). 8-Nitroquinoline (XVIII); 8-bromo-7-methoxyquinoline (XIX), 5-methoxy-8-nitroqninoline (XX), and 6-bromo-5, 7-dimethoxy-8-nitroquinoline (XXI). 4-Nitroquinoline (XXII); 4-bromo-3-methoxyquinoline (XXIIIa), 3-methoxy-4-nitroquinoline (XXIIIb), 2, 3-dimethoxy-4-nitroquinoline (XXIV) and 4-methoxyquinoline (XXV). The reaction of 2-nitroquinoline (XXX) gave only 2-methoxyquinoline (XXXI).

著者

横尾 信夫 服部 英三 平田 光輝 渡辺 好一郎 佐藤 文泰 永倉 正彦 藤井 節郎

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.107, no.9, pp.732-737, 1987-09-25 (Released:2008-05-30)

参考文献数

9

被引用文献数

1 1

---

Synthesis of water-soluble chymotrypsin specific inhibitors was attempted to study the roles of chymotrypsin-like enzymes in vivo. Previously we reported that the esters of carboxylic acid containing a condensed ring showed stronger activity than those containing a single ring system. Then we synthesized 4-substituted phenyl esters of carboxylic acid containing a condensed ring, such as tetralin, naphthalene, indole etc., and their inhibitory activities were compared. Among these compounds, esters of tetralin-1-carboxylic acid (FK-448) and 1-naphthylacetic acid showed the strongest activity, and their IC50 values were 8×10-7, 5×10-7 M, respectively. Tetralin-2-carboxylate and 2-naphthylacetate inhibited weaker than 1-analogues. Esters of basic quinoline carboxylic acid and bulky carboxylic acids containing a three-ring system inhibited poorly. Chymotrypsin produced equimolecular 4-substituted phenol rapidly and thereafter the amount of 4-substituded phenol increased slowly, when incubated with FK-448 at 37°C.

著者

津田 恭介

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.69, no.11, pp.486-488, 1949-11-25 (Released:2010-02-19)

参考文献数

15

著者

鈴木 順子 今津 嘉宏

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.5, pp.599-600, 2018 (Released:2018-05-01)