YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
128 巻, 6 号
選択された号の論文の17件中1~17を表示しています
誌上シンポジウム
  • 鳥居塚 和生, 津谷 喜一郎
    2008 年 128 巻 6 号 p. 835-836
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
  • 合田 幸広
    2008 年 128 巻 6 号 p. 837-838
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
      The safety guideline for voluntary inspections on the ingredients used for capsulated or pellet food, announced by the director of the department of food safety of the Ministry of Health, Labor and Welfare on February 1, 2008 states that “how to guarantee the origin” is the top priority to ensure safety. However, in the course of our continuous investigation of the origin of natural products, the ingredients of some health food products such as chondroitin sulfate, white kwao keur (Pueraria candollei var. mirifica) and black cohosh did not originate from the labeled material. The usage of the correct origin is the fist step for the quality assurance of “health food”. Therefore, we believe that regulatory requirements for accurately indicating the origin of “health foods” and effective enforcement of these requirements are needed.
  • 大濱 宏文
    2008 年 128 巻 6 号 p. 839-850
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
      The importance of supplements is well recognized both in the United States (US) and European Union (EU) as substances to maintain and promote health and to reduce the risk of various diseases. From a legal point of view, systems to regulate the health claims of products classified as supplements have been established in both the US and EU. The health claims are divided into two categories, that is, disease risk reduction claims and structure/function claims, and the claims must be substantiated with concrete scientific evidence. In particular, to substantiate the disease risk reduction claims, reliable human clinical studies, such as randomized controlled interventional trials, are acceptable as strong evidence. Evaluation of the safety of the ingredients for supplements is another important issue. The safety is mainly evaluated by means of risk analysis. However, the concept of risk-benefit analysis is gradually becoming more important than previous risk analysis techniques. The regulations for supplements and health claims currently enforced in both the US and EU are discussed in this article in comparison with the current regulatory systems applied to health foods in Japan.
  • 吉田 武美
    2008 年 128 巻 6 号 p. 851-857
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
      The nerve gas sarin has been responsible for tragic disasters in Matsumoto city, Nagano in 1994 and in the Tokyo subway system in 1995, which was a terrorist attack against non-military citizens. These chemical weapons exposures shocked the world, and have become sources of social concern. Thereafter there were several toxic substance-evoked incidents in Japan, specfically a poisoning due to curry containing arsenite at Wakayama city and foods and drinks containing other toxic chemicals. Following these tragic events, the Japanese government started to prepare a risk and medical management system for countering chemical and biological terrorism by developing a network of nationwide highly-sophisticated analytical instruments in police research institutes and emergency hospitals. Various ministries and National Research Institutes also provide information, guidelines and treatments for chemical and biological agents. In the event of an emergency such as a mass chemical exposure or mass food poisoning, information on “when, where, who, whom, what, how” should be reported rapidly and accurately to the first responding national organizations, such as police and fire departments, health care centers, and hospitals. Pharmaceutical scientists and pharmacists have been educated and trained on the handling of toxic chemical substances as well as drugs, and thus in the case of an event, they can become advisers for risk assessment and the analysis of drugs and chemicals. Japan has experienced food- and drink-poisonings as terrorism-like attacks. Poisonings caused by the herbicide paraquat and other pesticides including organophosphate insecticides, potassium cyanate and the above-mentioned arsenite-poisoned curry food have occurred. Because of easy access to internet-aided purchases of toxic substances and the import and export of foods, we must pay attention to possible massive exposures through foods and develop emergency management measufes to counter them.
  • 豊玉 速人
    2008 年 128 巻 6 号 p. 859-866
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
      It has become very easy to import drugs from overseas due to the spread of the Internet, and this has made the construction of a country-wide system that ensures safety a complicated matter. Although drug information and side-effect information databases are widely used, what is the situation concerning non-medicinal health foods that find their way into Japan from overseas? If the harmful effects of unknown substances can be prevented, it will be very beneficial. I would like to discuss these problems from the point of view of handling medical information.
  • 津谷 喜一郎, 詫間 浩樹
    2008 年 128 巻 6 号 p. 867-880
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
      Regulatory science began in the late 1980's in the pharmaceutical area in Japan. It aimed not only at vertical, top-down regulation but also horizontal regulation to suit the social value system. Herbal medicines and dietary supplements are two areas where regulatory science is still not well developed and used. Risk perception, risk assessment and risk management in these areas are often neglected by regulators, academicians and the public. Since the risk of using herbal medicines and dietary supplements is a global concern, development of a global regulatory system is needed. In this paper, we introduce the current situation of several projects which deal with regulatory science in herbal medicines and dietary supplements, namely: (1) Herbal ATC (HATC) classification project initiated by Uppsala Monitoring Centre (UMC) which led to the development of the provisional HATC code of 228 Kampo formulae and Standard Kampo Formula Nomenclature (SKFN) in Japan, (2) WHO/WPRO International Standardization of Terminology (IST) which resulted in the publication of “WHO Internal Standard Terminologies on Traditional Medicine in the Western Pacific Region Forum for Herbal Harmonization”, (3) Forum for the Harmonization of Herbal Medicines (FHH), (4) CONSORT extension for herbal medicines, (5) ICH M5 (Data elements and standards for drug dictionaries), and (6) activities on nomenclature at the International Organization for Standardization (ISO). However, there is a lack of coordination among these projects. Therefore, harmonization of all projects aimed at harmonizing and standardizing all aspects of regulatory science for herbal medicines and dietary supplements is recommended. However, careful consideration should be given to each unique local situation.
総説
  • 田邉 信三
    2008 年 128 巻 6 号 p. 881-900
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
      Inorganic sulfur compounds, such as S2−, SO32− and S2O32−, are produced from sulfur- containing amino acids as intermediary metabolites in mammalian tissues through complex pathways and are ultimately incorporated into sulfate. Reduced sulfur is also produced via the desulfuration of cysteine by several sulfurtransferases present in mammalian tissues; these enzymes include γ-cystathionase (γ-CST), and 3-mercaptopyruvate sulfurtransferase (3-MST). This reduced sulfur is then incorporated into pools of active reduced sulfur (sulfane sulfur; polysulfides, polythionates, thiosulfate, thiosulfonates and elemental sulfur) that are involved in the detoxication of cyanide and in the biosynthesis of iron-sulfur cluster. Sulfane sulfur is labile and is reduced to H2S by reducing agents. The physiological function of these sulfur species is less clear. We have found that a reduced sulfur species is commonly present in mammalian sera and tissues as a high molecular weight material and as both a high and a low molecular weight material, respectvively; we designated this sulfur species as “bound sulfur.” Bound sulfur can be easily liberated as sulfide by reduction with DTT. This review describes sensitive and specific assay method for determining the presence of inorganic sulfur compounds as well as bound sulfur and related sulfurtransferases in biological samples. The physiological functions of bound sulfur in rat tissues were also evaluated using these assay methods. Bound sulfur was found to be located primarily in the rat liver cytosolic fraction in the form of high molecular weight components. The capacity of bound sulfur production was enriched in the cytosol fraction and depended on γ-CST. Bound sulfur also affected redox regulation by modifying active thiol residues in some liver cytosol enzymes and effectively inhibited cytochrome P-450-dependent lipid peroxidation induced by CCl4 and t-BuOOH.
  • 祐田 泰延
    2008 年 128 巻 6 号 p. 901-917
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
      The authors' researches have been focused on pathogenic, physiological and biochemical mechanisms in hypertension and diabetes. Studies on hypertension were performed using salt-sensitive hypertensive Dahl rats as compared with the corresponding normotensive rats. Especially, implication with mobilization of electrolytes such as sodium, potassium, calcium and magnesium in hypertension gave rise to provocative to the author. Furthermore, complications of diabetes with hypertension were themes for the authors' researches. Thus, sodium-dependent glucose transport has been studied on sodium-dependent glucose transporters such as SGLT1 and SGLT2 using cell lines of porcelain renal cell, LLC-PK1, and murine renal cell, NRK-52E. Relationship between magnesium mobilization and NO in hypertension has been explored using renal epithelial cell-lines and salt-sensitive hypertensive Dahl rats in the latter half of the author's research life.
  • 中園 学
    2008 年 128 巻 6 号 p. 919-924
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
      Fluorescence (FL), chemiluminescence (CL) and bioluminescence (BL) have been extensively focused on luminescence assays. Various FL and CL compounds have been synthesized and evaluated their FL and CL properties. This review describes development of highly selective and sensitive FL and CL reagents by derivatizing luminol, indole and polyphenol. Luminol derivatives were used for measuring enzyme activities and ultraviolet ray power. Indole derivatives with large stokes shift and long-lasting CL properties were developed. Compound which had enhancement effect on polyphenol CL was found. Highly sensitive CL polyphenol dendrimers were synthesized.
一般論文
  • 濃沼 政美, 小池 勝也, 中村 均
    2008 年 128 巻 6 号 p. 925-931
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
      We developed a new survey analysis technique to understand students' actual aims for effective pretraining prior to clinical practice. We asked third-year undergraduate students to write fixed-style complete and free sentences on “preparation of drug dispensing.” Then, we converted their sentence data in to text style and performed Japanese-language morphologic analysis on the data using language analysis software. We classified key words, which were created on the basis of the word class information of the Japanese language morphologic analysis, into categories based on causes and characteristics. In addition to this, we classified the characteristics into six categories consisting of those concepts including “knowledge,” “skill and attitude,” “image,” etc. with the KJ method technique. The results showed that the awareness of students of “preparation of drug dispensing” tended to be approximately three-fold more frequent in “skill and attitude,” “risk,” etc. than in “knowledge.” Regarding the characteristics in the category of the “image,” words like “hard,” “challenging,” “responsibility,” “life,” etc. frequently occurred. The results of corresponding analysis showed that the characteristics of the words “knowledge” and “skills and attitude” were independent. As the result of developing a cause-and-effect diagram, it was demonstrated that the phase “hanging tough” described most of the various factors. We thus could understand students' actual feelings by applying text-mining as a new survey analysis technique.
  • 久間 將義, 松田 紗苗, 柴山 裕治, 岩城 政宏
    2008 年 128 巻 6 号 p. 933-940
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
      A novel amphiphilic vitamin C derivative, disodium isostearyl 2-O-L-ascorbyl phosphate (VCP-IS-2Na) possessing an alkyl chain of C18 to a stable ascorbate derivative sodium L-ascorbic acid 2-phosphate (VCP-Na), was synthesized and evaluated as an anti-mutagen with suppressive effect on SOS-inducing activity on mutagen in the Salmonella typhimurium TA1535/pSK1002 umu test. VCP-IS-2Na was assayed with chemical mutagens, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide (furylfuramide) and 4-nitroquinolin 1-oxide (4NQO), which do not require liver metabolizing enzymes. VCP-IS-2Na at a concentration of 0.40 μmol/ml suppressed 66.2%, 54.7% and 60.2% of the SOS-inducing activity on MNNG, furylfuramide, and 4NQO, and the 50% inhibitory dose value (ID50) was 0.12 μmol/ml, 0.26 μmol/ml, and 0.17 μmol/ml, respectively. In addition, VCP-IS-2Na was assayed with 2-aminoanthracene (2AA) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which require liver metabolizing enzymes. To study the structure-activity relationship, L-ascorbic acid (VC) and VCP-Na were also assayed with all mutagens. VCP-IS-2Na, suppressed the chemical and physical mutagens-induced SOS response greater than VC and VCP-Na in the umu test. Also, the antimutagenic activities of VCP-IS-2Na, VC, and VCP-Na against MNNG and Trp-P-1 were assayed by the Ames test using the S. typhimurium TA100 strain. In summary, this research suggests that VCP-IS-2Na showed potent antimutagenic effects against chemical mutagens and UV irradiation.
  • Yongzhong WANG, Yajuan LI, Qingsong WANG, Jiang WU, Xiaoling FANG
    2008 年 128 巻 6 号 p. 941-950
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
      A mixed polymeric micelle formulation of paclitaxel (PTX) has been developed with the purpose of improving the solubility and prolonging the time of blood circulation of PTX in comparison to current Taxol injection. The mixed micelles were prepared by thin-film method using a nonionic surfactant Pluronic P105, L101 and PTX. The mean size of PTX-loaded mixed micelles was 185 nm with narrow size distribution shown by a dynamic light scattering sizer and a transmission electron microscopy. The in vitro release profiles indicated that PTX release from the mixed micelles exhibited a sustained release behavior. A similar phenomenon was also observed in a pharmacokinetic assessment in rats, in which t1/2β and AUC of the mixed micelle formulation were 5.5 and 4.9-fold higher than that of Taxol injection. The biodistribution study in mice showed that the PTX-loaded mixed micelles not only decreased drug uptake by liver, but also prolonged drug retention in blood, and increased distribution of the drug in lung, spleen and kidney. These results suggested that the mixed polymeric micelles may efficiently load, protect and retain PTX in both in vitro and in vivo environments, and could be a useful drug carrier for intravenous administration of PTX.
  • 櫻井 雅人, 尾関 有一, 安藤 正樹, 岡本 浩一, 檀上 和美
    2008 年 128 巻 6 号 p. 951-957
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
      One-step dry-coated tablets (OSDrC), which are useful as colon-targeting drugs, were prepared using Eudragit L 100-55 (Eud-L) and chitosan (Chit) as an outer layer. The lag time of OSDrC with an outer layer of Eud-L : Chit at a ratio of 3 : 1 in each test medium was greater than the gastric emptying time in the first fluid simulating the stomach and was greater than the small intestine transit time in phosphate buffer (pH 7.4) simulating the small intestine. Drug-release profiles of OSDrC were evaluated under test conditions considering the amount of gastric acid and bile acid, as well as the amount of fluid in the colon. The lag time of OSDrC was greater than the gastric emptying time in test medium simulating the stomach and greater than the small intestine transit time in test medium simulating the small intestine, although it was affected by the amount of gastric acid and bile acid. Drug release from OSDrC was completed within the colonic transit time in the test medium simulating the colon, although it was affected by the amount of fluid in the colon. Therefore the prepared OSDrC were found to permit drug delivery to the colon.
ノート
  • 山本 佳代, 小島 昌徳, 井口 博文, 太田 隆文
    2008 年 128 巻 6 号 p. 959-964
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
      Although fentanyl patches (FP) designed to sustain plasma fentanyl concentrations for 3 days are used in many patients for continuous relief of moderate to severe cancer pain, there are some cases in which effective pain relief is sustained less than for 3 days, and in which plasma fentanyl concentrations rapidly decrease at the third day after the application. In this study, we measured the amount of fentanyl remaining in FP after continuous 3-days use to clarify some clinical factors that can influence the remaining amounts in 4 patients. Average estimated fentanyl-dermal transfer rates of the collected 41 patches calculated from their remaining amounts were less than nominal rates (21.2±3.4 cf. 25 μg/h (2.5 mg FP); 44.9±5.1 cf. 50 μg/h (5 mg FP)). Intra-individual variability was also observed (CV: 6.6-14.3% (2.5 mg FP), 3.9-13.3% (5 mg FP)). The present study suggests that the estimated fentanyl-dermal transfer rates are affected by fever, patients' body mass index and application sites. Although further study is necessary to elucidate factors that can influence the variability in transdermal fentanyl absorption, the approach in this study would contribute to improving appropriate usage of FP.
  • 堤 きく江, 土屋 千佳子, 花輪 和己, 鈴木 正彦, 花輪 剛久, 小口 敏夫
    2008 年 128 巻 6 号 p. 965-970
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
      Beraprost sodium (BPS) is often used for pediatric patients with pulmonary hypertension. The purpose of this study was to determine the expiration date of the powdered medicine prepared by grinding tablets. In the present study, the hygroscopicity and stability of the beraprost tablet (DORNER® tablet), ground Dorner tablet and powder formulation (Doener powder) consisting of the ground DORNER® tablet and lactose (EFC® lactose) were investigated after storage at various relative humidities (RHs) and light exposures. While the DORNER® tablets and ground DORNER® tablets were found to adsorb significant amounts of water vapor at an RHs of greater than 51.0%, Dorner powder scarcely adsorbed water. The stability of BPS in the Dorner powder decreased after storage under 3000 lux for 90 days. From these results, the expiration date and storage conditions of Dorner powder were determined to “90 days without exposure to light.” We also investigated the stability of BPS in solutions of various pH values on the assumption that Dorner powder may be given to pediatric patients after dissolving in soft drinks. Because BPS degraded significantly below pH 2, pharmacists should alert patients not to take Dorner powder with acidic soft drinks.
資料
  • 花尻(木倉) 瑠理, 河村 麻衣子, 内山 奈穂子, 緒方 潤, 鎌倉 浩之, 最所 和宏, 合田 幸広
    2008 年 128 巻 6 号 p. 971-979
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
      In the last 10 years, many analogs of narcotic substances have been widely distributed in Japan as easily available psychotropic substances and this has become a serious problem. They have been sold as video cleaners, incense and reagents via the Internet or in video shops. They are not controlled under the Narcotics and Psychotropics Control Law because their pharmacological effects have not yet been proved scientifically. As a countermeasure to prevrent the abuse fo these substances, the Ministry of Health, Labor and Welfare amended the Pharmaceutical Affairs Law in 2006 so thet 31 non-controlled psychotropic substances (11 tryptamines, 11 phenethylamines, 6 alkyl nitrites, 2 piperazines and salvinorin A) and 1 plant (Salvia divinorum) are now controlled as “Designated Substances (Shitei-Yakubutsu)” as of April 2007. Five other compounds (4 phenethylamines and 1 piperazine) were also added to this category in January 2008. In this study, we developed simultaneous analytical methods for these designated substances using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) and present retention times, UV spectra, electron ionization (EI), GC-MS, and electrospray ionization (ESI) LC-MS data.
  • 内山 奈穂子, 河村 麻衣子, 鎌倉 浩之, 花尻(木倉) 瑠理, 合田 幸広
    2008 年 128 巻 6 号 p. 981-987
    発行日: 2008/06/01
    公開日: 2008/06/01
    ジャーナル フリー
      Many psychotropic substances are readily available in Japan via the Internet. To avoid the spread of drug abuse, some drugs have been controlled as designated substances (Shitei-Yakubutsu) in Japan since 2007 by the Pharmaceutical Affairs Law. Twenty-nine designated substances (classified as tryptamine, phenethylamine and piperazine types) were analyzed using color tests and TLC. The color tests were examined with the Marquis, Ehrlich, Simon's, Liebermann-Burehard's, and Mandelin reagents. The color of β-carbonyl-methylenedioxyphenetylamines produced by the Marquis reagent was yellow, and 4-halo-2,5-dimethoxy phenethylamines reacted with the Marquis reagent to a give deep yellow-green and/or a deep green color. Although all designated substances of the tryptamine type reacted with the Ehrlich reagent to give a brown color, only 1-(2,4,6-trimethoxyphenyl) propan-2-amine (TMA-6) among the phenethylamines showed a red color on treatment with the reagent. However, 3,4,5-trimethoxy and 2,4,5-trimethoxy isomers of TMA-6 were not colored with the reagent. Thus, TMA-6 could be distinguished from isomers using the Ehrlich reagent. We also analyzed the designated substances with thin-layer chromatography developed with two different solvent conditions. All substances were detected by UV254 nm and an iodoplatinate reagent. These results suggest that color tests and TLC, followed by GC-MS and LC-MS analyses, can be used for preliminary identification of designated substances.
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