著者

永田 亘 成定 昌幸 吉岡 美鶴 吉田 正 尾上 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.111, no.2, pp.77-102, 1991-02-25 (Released:2008-05-30)

参考文献数

60

被引用文献数

1 5

---

A pioneering work in the field of oxacephem antibiotics which had been carried out in our research laboratories is reviewed. Our research of β-lactam antibiotics was started in 1974 with the policy to make chemical modification at the nuclei but not the side chain of the existing β-lactam antibiotics, with an expectation to discover a new type of antibiotics. After the success in establishing an efficient synthetic method for 3'-nor-cephalosporin, we started oxacephem research in 1975. We succeeded in developing three synthetic methods starting from penicillins which efficiently served to prepare numerous oxacephem (1-oxa-1-dethia-cephalosporin) derivatives. It turned out that the oxacephem nucleus was much more distorted with an increased ring strain, resulting in reduction of the β-lactam amide resonance to a greater extent than the cephalosporin nucleus. This physicochemical properties conferred an increased chemical reactivity on the nucleus as evidenced by an increased hydrolysis rate as compared with the corresponding 1-thia counterpart. This increased chemical reactivity coupled with the reduced hydrophobicity of the oxacephem nucleus as evidenced by the lower distribution constant in a water-octanol system, characterized unique biological properties of oxacephem derivatives. These include (1) 2-16 times increase in antibacterial activity with emphasis against gram-negative bacteria ; (2) increased protecting effect in vivo parallel to the increased in vitro activity ; (3) reduction of the stability to β-lactamases leading to decreased antibacterial activity against the β-lactamase producing strains ; (4) 1.6-3.2 times increase in penetrability through the outer membrane of certain gram-negative bacteria, the increase being due to the increased hydrophilicity of the oxacephem nucleus ; (5) remarkably reduced binding to human serum albumin improving the efficacy of the oxacephems in the blood ; (6) a remarkable change in the excretion pattern, i.e. recovery in the bile reduced and that in the urine increased. These biological characteristics are generally favorable for antibacterial agents against pathogenic diseases except for the reduced stability to β-lactamases. This unfavorable property of the oxacephem nucleus was the only barrier for developing a new agent of the oxacephem nucleus. However, this problem was relatively easily solved by introduction of (1) the methoxy group at 7α and (2) appropriately α-substituted acyl amide side chain at 7β ; the former and the latter substituent effectively stabilized the oxacephems to various kinds of penicillinases and cephalosporinases, respectively. It turned out that both effects were complementary and, thus, combination of both substituents produced perfect stabilization of the oxacephems to β-lactamases, and brought about the complete recovery of the activity against resistant strains. Extensive studies were performed to obtain deep and broad knowledge in structureactivity relationships in the field of the newly explored oxacephems. As the results of these efforts we succeeded in obtaining two important and useful oxacephem compounds, i.e. latamoxef 18 and flomoxef 19. Latamoxef 18 is a very potent and broadly active third generation β-lactam antibiotic, and perfectly stable to various kinds of β-lactamases showing efficacy against most of the resistant bacteria. Moreover, it has very favorable pharmacological properties, such as a high blood level and a long half-life, which are essential for efficacy in human body. One of the drawback of this antibiotic, as commonly observed in the third generation antibiotics, was the rather weak activity against grampositive bacteria, especially against Staphylococcus aureus. This weak point was basically improved by introducing a new 7β-acylamido side chain and by a minor structural change in the N-methyl-tetrazol part, as seen in structure 19. [the rest omitted]

著者

清水 當尚 宇野 準 伊藤 継孝 増田 義信 黒川 美貴雄

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.116, no.7, pp.533-547, 1996-07-25 (Released:2008-05-30)

参考文献数

55

被引用文献数

4 8

---

Zonisamide (1, 2-benzisoxazole-3-methanesulfonamide, AD-810) is a broad spectrum antiepileptic drug which has been launched in Japan and South Korea. It lacks the ureide structure included in most of the existing antiepileptic drugs. Zonisamide was synthesized by the sulfonation and the successive amination of 1, 2-benzisoxazole-3-acetic acid in a very poor yield. After several efforts to optimaize the compound, zonisamide was selected based on the balance of the efficacy and safety. The yield was greatly improved by the development of new synthetic routes. Zonisamide suppressed maximal electroshock seizures in mice, rats, rabbits and dogs. Its therapeutic plasma concentration range between anticonvulsant and neurotoxic effects was much wider than that of the existing antiepileptic drugs. In electroencephalographic studies on animal models of epilepsy, zonisamide, like phenytoin and carbamazepine, restricted the spread or propagation of seizures and, like sodium valproate, it suppressed the epileptogenic focus activity. Zonisamide was effective in several kindling models. In clinical studies, zonisamide exerted the efficacy against partial seizures (simple, complex, secondarily generalized seizures) and some generalized seizures (tonic-clonic, tonic, atypical absence seizures) that were comparable to that of carbamazepine and sodium valproate, respectively. Zonisamide was also effective in monotherapy. The adverse effects related with zonisamide were mainly drowsiness, ataxia, loss of appetite and gastrointestinal symptoms. Serious adverse effects which may be life-threatening have not been reported.

著者

柴崎 正勝

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.101, no.12, pp.1073-1091, 1981-12-25 (Released:2008-05-30)

参考文献数

69

被引用文献数

2 3

---

The present article describes our recent synthetic studies on various biologically active compounds, including synthesis and biological properties of prostacyclins, synthetic approach toward thromboxanes, and total syntheses of coriolin and hirsutic acid C. In the final part of this review, some new reactions, exploited in connection with synthetic studies on prostacyclins, are also described.

著者

坪島 正巳 松本 公一郎 新井 義信 若塚 弘久 川崎 晃義

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.7, pp.447-469, 1992-07-25 (Released:2008-05-30)

参考文献数

54

被引用文献数

3 4

---

The therapeutic use of prostaglandins (PGs) which contain various biological activities and are unstable was successfully achieved. PGs were produced in a large scale according to the Corey method and could be stabilized by the formation of a clathrate compound with cyclodextrin, which enabled the production of marketable form of highly pure PGs. Diligence in the development of native PGs and their structural analogs for human therapy resulted in the following six drugs now being on the market in Japan : PGF2α as the first drug of PGs in the world which induces labor ; PGE2 as an orally active labor inducing drug ; PGE1 for the treatment of peripheral vascular diseases ; gemeprost for therapeutic abortion in the middleterm ; ornoprostil, as an oral anti-ulcer agent ; limaprost for the treatment of peripheral vascular diseases as an oral agent.

著者

鶴田 峯生 三ケ島 浩 大江 孝範 川崎 和幸 瀬戸口 信郎 中 洋一 田原 哲治

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.109, no.1, pp.33-45, 1989-01-25 (Released:2008-05-30)

参考文献数

28

被引用文献数

7 5

---

Several imidazolylpyridinemethanols and imidazolylbenzenemethanols were prepared and evaluated for an inhibitory activity against arachidonic acid-induced platelet aggregation. The result shows that the arylmethanol moiety is essential for the activity and may correspond to the 15-OH group of prostagrandin H2 (PGH2). Among the compounds tested, 4-[α-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3, 5-dimethylbenzoic acid (XV) was found to have a potent inhibitory activity and a long duration of action. Structureactivity relationships are also discussed briefly.

著者

坂井 進一郎 山中 悦二 横溝 理 松本 緑

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.95, no.12, pp.1511-1516, 1975-12-25 (Released:2008-05-30)

参考文献数

10

被引用文献数

1 2

---

It has been found that a reaction of the cyclic imino ether in gardneramine (I) with MeI afforded N-methylated oxindole (III). Synthesis of a compound (XIV)) having a cyclic imino ether system and its reaction with MeI are described. An alcohol (X) was prepared by the Michael reaction of N-acetyl-3-ethyloxindole (VII) with ethyl acrylate, followed by LiA1H4 reduction. On treatment with p-toluenesulfonyl chloride in pyridine, X afforded a tosylate (XI) and a chloride (XII). The imino ether (XIV), synthesised by the reaction of XII with potassium t-butoxide in dimethyl sulfoxide-benzene (1 : 1), reacted with MeI to afford N-methyl-3-(3-iodopropyl)oxindole (XX). The reductive dehalogenation of XX with NaBH4/Me2SO gave N-methyl-3-ethyl-3-propyloxindole (XXI), which was identical with the authentic sample prepared from XII by a different route.

著者

古谷 力

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.106, no.10, pp.856-866, 1986-10-25 (Released:2011-01-31)

参考文献数

25

被引用文献数

3 3

---

Plant tissue culture is profitably used in biotechnology today to produce valuable compounds and to rapidly and uniformly propagate economically important plants.The main objective of this review is to outline the advances in the production of medicaments and biochemicals by plant tissue cultures. In relation to this objective, the development of newly advanced techniques such as transformation, cell fusion, biotransformation, bioreactor with immobilized plant cells, and synthetic seeds, is briefly discussed.Recent studies in my laboratory on the bioconversion of 2-phenylpropionic acid (mainly glycosylation) and l-menthol (glycosylation and hydroxylation) by plant suspension cells, and of codeinone (reduction) by the bioreactor with immobilized opium poppy cells, and on the de novo synthesis of stress metabolites in the immobilized licorice cells, are described. The production of Korean ginseng and saponin ginsenosides in Korean ginseng suspension cells, and of Vitamin E in safflower cells are also discussed.

著者

森口 郁生

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.114, no.3, pp.135-146, 1994-03-25 (Released:2008-05-30)

参考文献数

39

被引用文献数

3 3

---

Recent development of quantitative structure-activity relationships (QSARs) and computer-aided drug design contributed by the author and his coworkers was briefly reviewed. Fuzzy adaptive least-squares (FALS), a pattern recognition method for analysing structure-activity rating data to generate QSAR models was developed. A novel feature of FALS is that the degree to which each sample belongs to its activity class is given by a fuzzy membership function. Using FALS, non-congeneric QSAR analyses of carcinogenicity, mutagenicity, and six kinds of pharmacokinetic properties of miscellaneous organic chemicals were performed to construct predictive models for drug design. In these QSAR analyses, the values of log P (partition coefficient in octanol/water) calculated by the simple method of Moriguchi et al. were used as the descriptor for hydrophobicity. The method of Moriguchi et al. is not only simple and convenient but also reliable in the application to 22 drugs selected by Rekker et al. compared to the Rekker method and the Hansch-Leo method. Lastly, a heulistic search method for active conformers using molecular mechanical confor-mational analysis and principal component analysis was proposed.

著者

上野 勝次郎 岡田 清三郎

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.82, no.4, pp.532-535, 1962-04-25 (Released:2010-02-19)

参考文献数

10

---

Dornow and others synthesized 2-aminonicotinic acid derivatives by the condensation of β-diketone and amidine or imino ethers. Pyridine cyclization by the condensation of β-diketones with non-symmetrical structure and malonamideamidine or ethyl 3-amino-3-ethoxyacrylate was examined and a new derivative of 2-aminonicotinic acid derivatives, which may serve as intermediate for synthesis of pyridoxine, were obtained. The compounds synthesized were ethyl 2-amino-4-ethoxymethyl-6-methylnicotinate, diethyl 2-amino-6-methyl-3, 4-pyridinedicarboxylate, and ethyl 2-amino-4-carbamoyl-6-methylnicotinate, and their structures were determined.

著者

首藤 紘一

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.10, pp.987-995, 2000-10-01 (Released:2008-05-30)

参考文献数

30

被引用文献数

2 3

---

Cancer is a common life-threatening disease. Prevention and therapy of the disease are the desire of everybody. This paper summarizes our attempt to the tough challenge. Chronologically we began the study of carcinogenesis, and then turned to the research of anticancer agents. Identification of food mutagens was extensively studied. Once they were identified, the mechanism of nucleic acid modifications by these mutagens had been studied. The modification study gave information on the nucleic acid modification by mitomycin and bleomycin. The structure-activity relationship study of phorbol esters and teleocidines whose tumor promotion is epigenetic, was extensively studied. On the other hand, retinoic acid, a vitamin A metabolite, suppresses the epigenetic tumor promotion. This suggests that an epigenetically active compound rather than a cytotoxic anticancer agent can be used for tumor suppression. In the retinoid research, we found a number of characteristic new active substances which may be of therapeutic use : some of them are in the clinical trial stages in the field of dermatology and cancer. During the chemical study of retinoids, we encountered the retinoic acid receptor, coded by the retinoic acid receptor (RAR) gene which had just reported. Further retinoid research yielded retinoids antagonists, and then RXR(retinoic acid-X-receptor)-agonists and RXR-antagonists. These ligands have a big potential in the therapy of diabetes and obesity.

著者

川島 嘉明

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.106, no.6, pp.433-445, 1986-06-25 (Released:2011-01-31)

参考文献数

34

被引用文献数

1

---

A novel agglomerated crystallization technique, termed spherical crystallization technique, which can transform fine crystals precipitated into spherical agglomerates in one step during the crystallization process, has been developed by using new agglomeration phenomena of particles in liquid system. In this technique, a binary or a ternary mixture of partially miscible solvents was used as a crystallization solvent. It was found that by choosing the proper proportion of the mixture, a small amount of immiscible liquid was liberated from the system, which could preferentially wet the crystals, forming spherical agglomerates. By using this technique, needle like crystals of salicylic acid were agglomerated into spheres being directly compressible into tablet. Spherically agglomerated crystals of aminophylline were prepared directly by reacting theophylline with ethylenediamine in an alcohol-organic solvent-water mixture. The spherically agglomerated crystals of new complex of indomethacin and epirizole with increased solubilities were prepared. Controlled release microspheres of ibuprofen with acrylic polymer were prepared to improve bioavailability.

著者

梁井 光二

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.70, no.4, pp.181-184, 1950-04-25 (Released:2010-02-19)

著者

三木 卓一 松尾 泰介

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.87, no.3, pp.323-325, 1967-03-25 (Released:2008-05-30)

参考文献数

17

被引用文献数

2 12

著者

芦澤 一英 内川 清彦 服部 禎一 石橋 泰雄 三宅 康夫 里 忠

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.3, pp.191-201, 1990-03-25 (Released:2008-05-30)

参考文献数

45

被引用文献数

1 2

---

In designing the dosage form, one major factor controling their physicochemical properties is solid forms of the drug powder. The method for improving the physicochemical stability of unstable β-lactam antibiotics is very important. E1040 is a novel parenteral 3-betaine type cephalosporin which has a broad antibacterial spectrum and potent activities against Citrobacter, freundii, Enterobacter cloacase, and glucose-nonfermentative bacteria, including P. aeruginosa. The present study was intended to provide the solid-state chemical stability of perenteral steril dry dosage form of E1040. The chemical stability differences among the various solid forms, dry amorphous, additive freeze dried amorphous solid and crystalline powder, were evaluated as a function of temperature by thermo stress tests. Freeze dried anhydrous amorphous form was the first steril dry dosage form investigated during the preformulation study. However, this compound is chemically unstable, in the titer of them, reduction are observed in the freeze dried amorphous solid. In order to select the most suitable solid form of E1040, two methods were used. One was crystalline solid and the other was NaCl additive freezedried formulation. Through our experiments, the solid-state chemical stabilization can be achieved by these two methods (effect of crystal structure and effect of NaCl additive).

著者

三井 幸雄

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.100, no.6, pp.585-601, 1980-06-25 (Released:2008-05-30)

参考文献数

72

---

There are two different techniques for the X-ray structure analyses of materials ; that for small molecules and that for macromolecules. The latter technique, is called"protein crystallography."The characteristics of protein crystallography as opposed to ordinary crystallography for small molecules are described. Some of the achievements of protein crystallography and their impact on other scientific fields are discussed, and perspectives for the possible contribution of protein crystallography to molecular pharmacology are given.

著者

大村 貞文 森本 繁夫 長手 尊俊 安達 孝 河野 喜郎

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.112, no.9, pp.593-614, 1992-09-25 (Released:2008-05-30)

参考文献数

60

被引用文献数

7 18

---

A series of O-alkylated derivatives of erythromycin (EM) has been prepared and their biological properties were evaluated. Among them, clarithromycin (CAM, 6-O-methylerythromycin) exhibits most potent in vitro and in vivo antibacterial activities, higher acid-stability than EM and favorable pharmacokinetic properties as an antibiotic. CAM was originally synthesized via methylation of 2'-O, 3'-N-bis (benzyloxycarbonyl)-N-demethylerythromycin in low yield, because of the less selectivity of 6-O-methylation. The selective 6-O-methylation was achieved using the erythromycin 9-oxime derivative as a key intermediate. By the further investigation on the protective groups of 9-oxime and desosamine moiety, the production process of CAM on an industrial scale has been established via methylation of 2', 4"-O-bis (trimethylsilyl) erythromycin 9-[O-(1-isopropoxycyclohexyl) oxime] in more than 45% overall yield. CAM has the same antibacterial spectra as EM and is active against aerobic Gram-positive bacteria, some Gram-negative bacteria, anaerobic bacteria, Mycoplasma and Chlamydia. The activity of CAM against clinical isolates was 1 to 16 times higher than that of EM. The efficacies of CAM were 6 to 15 times superior to those of EM against systemic infections due to Gram-positive bacteria in mice. CAM also showed more potent therapeutic efficacies than EM against respiratory tract infections caused by S. pneumoniae and H. influenzae. CAM was well absorbed after oral administration, and its distribution to various tissues was significantly higher than that of EM in animals. The level of CAM in the lung was extremely high, which accounted 69 times that of EM. CAM was found to be distributed predominantly in the alveolar wall, especially in the alveolar epithelial cells, by microautoradiography. After oral administration in human, the serum level and urinary excretion of CAM were 5 and 20 times higher than those of EM, respectively. The major and active metabolite of CAM in human, (14R)-14-hydroxyclarithromycin, existed in significant quantity in the serum and urine, suggesting that the metabolite contributes to the excellent clinical efficacy of CAM. This paper describes the synthesis, structure-activity relationships, antibacterial activities, metabolism and clinical efficacies of CAM, a new macrolide antibiotic.

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

---

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.